4 5776333354982966032

Ahmed H.
Al-Salem
An Illustrated Guide
to Pediatric Urology
123
An Illustrated Guide to Pediatric Urology
Ahmed H. Al-Salem
An Illustrated Guide
to Pediatric Urology
Ahmed H. Al-Salem
Pediatric Surgery
AlSadik Hospital
Qatif
Saudi Arabia
ISBN 978-3-319-44181-8 ISBN 978-3-319-44182-5 (eBook)

DOI 10.1007/978-3-319-44182-5
Library of Congress Control Number: 2016957149
© Springer International Publishing Switzerland 2017

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exempt from the relevant protective laws and regulations and therefore free for general use.
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Springer Cham Heidelberg New York Dordrecht London

This Springer imprint is published by Springer Nature
Preface
The field of pediatric urology is rapidly growing and currently it is considered

as a subspecialty. Pediatric urologists and pediatric surgeons care for newborns,
infants, and children with congenital and acquired urological conditions. I have
written this book with more than 20 years’ experience in the care of infants and
children with urological conditions and hope it will help all those involved in
the surgical care of infants and children with urological problems. This book is
written in a simple way and easy to read. It covers most areas in the field of
pediatric urology with emphasis on the most important points relevant to the
patient’s presentation, diagnosis, and management. This book is well illustrated
and includes clinical, operative, radiological, and hand-drawn illustrations. I
hope it will be useful to consultant pediatric urologists, pediatric surgeons, spe-
cialists, fellows, and residents. This book should be useful also to general prac-
titioners, general surgeons, accident and emergency doctors, pediatricians,
neonatologists, trainees, medical students, and nurses.
Qatif, Saudi Arabia Ahmed H. Al-Salem
v
Acknowledgments
I would like to express special thanks of gratitude to my family who sup-

ported me and made this project possible. I would also like to thank all my
patients and their families.
vii
Contents
1 Congenital Urological Malformations . . . . . . . . . . . . . . . . . . . . . 1

1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Normal Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.3 Abnormalities of the Kidney . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3.1 Renal Agenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.3.2 Renal Hypoplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.3.3 Supernumerary Kidneys. . . . . . . . . . . . . . . . . . . . . . . 7
1.3.4 Renal Dysplasia and Multicystic Kidney . . . . . . . . . . 8
1.3.5 Polycystic Kidney Disease . . . . . . . . . . . . . . . . . . . . . 8
1.3.6 Simple (Solitary) Renal Cyst . . . . . . . . . . . . . . . . . . . 11
1.3.7 Renal Fusion and Renal Ectopia . . . . . . . . . . . . . . . . 12
1.3.8 Horseshoe Kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.3.9 Crossed Fused Renal Ectopia. . . . . . . . . . . . . . . . . . . 15
1.3.10 Ectopic Kidney. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
1.4 Abnormalities of the Ureter . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.5 Abnormalities of the Bladder . . . . . . . . . . . . . . . . . . . . . . . . . 22
1.6 Abnormalities of the Penis and Urethra in Males . . . . . . . . . 33
1.7 Abnormalities of Female External Genitalia . . . . . . . . . . . . . 36
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
2 Hydronephrosis in Infants and Children . . . . . . . . . . . . . . . . . . 43
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
2.2 Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
2.3 Etiology of Hydronephrosis . . . . . . . . . . . . . . . . . . . . . . . . . . 49
2.4 Classification of Hydronephrosis . . . . . . . . . . . . . . . . . . . . . . 55
2.5 Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
2.6 Investigations and Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . 58
2.7 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
2.8 Antenatal Hydronephrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
3 Pelviureteric Junction (PUJ) Obstruction . . . . . . . . . . . . . . . . . 71
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
3.2 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
3.4 Etiology of PUJ Obstruction . . . . . . . . . . . . . . . . . . . . . . . . . 74
3.6 Diagnosis and Investigations . . . . . . . . . . . . . . . . . . . . . . . . . 79
ix
x Contents
3.7 Management of Newborns with PUJ Obstruction . . . . . . . . . 88

3.8 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
3.9 Post-operative Complications and Follow-Up . . . . . . . . . . . . 97
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
4 Renal Tumors in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
4.2 Wilms’ Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
4.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
4.2.2 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
4.2.3 Histopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
4.2.4 Nephroblastomatosis . . . . . . . . . . . . . . . . . . . . . . . . . 108
4.2.5 Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
4.2.6 Risk Factors for Wilms’ Tumor . . . . . . . . . . . . . . . . . 112
4.2.7 Staging of Wilms Tumor . . . . . . . . . . . . . . . . . . . . . . 113
4.2.8 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
4.2.9 Prognosis and Complications of Wilms Tumor . . . . . 121
4.2.10 Surgical Considerations . . . . . . . . . . . . . . . . . . . . . . . 123
4.2.11 Surgical Complications . . . . . . . . . . . . . . . . . . . . . . . 130
4.2.12 Prognosis and Outcome . . . . . . . . . . . . . . . . . . . . . . . 130
4.2.13 Extrarenal Wilms’ Tumors . . . . . . . . . . . . . . . . . . . . . 131
4.3 Mesoblastic Nephroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
4.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
4.3.2 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
4.3.3 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
4.3.4 Histopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
4.3.6 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
4.3.7 Treatment and Prognosis . . . . . . . . . . . . . . . . . . . . . . 138
4.4 Clear Cell Sarcoma of the Kidney (CCSK) . . . . . . . . . . . . . . 138
4.4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
4.4.2 Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
4.4.4 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
4.4.5 Histopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
4.4.6 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
4.4.7 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
4.5 Malignant Rhabdoid Tumor of the Kidney . . . . . . . . . . . . . . 143
4.5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
4.5.2 Etiology and Pathophysiology . . . . . . . . . . . . . . . . . . 144
4.5.3 Histologic Findings . . . . . . . . . . . . . . . . . . . . . . . . . . 144
4.5.5 Investigations and Diagnosis . . . . . . . . . . . . . . . . . . . 146
4.5.6 Treatment and Outcome . . . . . . . . . . . . . . . . . . . . . . . 149
4.5.7 Mortality/Morbidity . . . . . . . . . . . . . . . . . . . . . . . . . . 150
4.6 Renal Cell Carcinoma in Children . . . . . . . . . . . . . . . . . . . . . 150
4.6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
4.6.2 Histopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Contents xi
4.6.3 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

4.6.4 Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
4.6.6 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
4.6.7 Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
4.6.8 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
4.7 Angiomyolipoma of the Kidney . . . . . . . . . . . . . . . . . . . . . . 156
4.7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
4.7.2 Histopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
4.7.3 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
4.7.5 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
4.8 Renal Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
4.8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
4.8.2 Etiology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . 159
4.8.3 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
4.9 Ossifying Renal Tumor of Infancy. . . . . . . . . . . . . . . . . . . . . 162
4.10 Metanephric Adenoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
4.10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
4.10.2 Histopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
4.10.3 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
4.10.5 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
4.11 Multilocular Cystic Renal Tumor . . . . . . . . . . . . . . . . . . . . . 165
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
5 Multi Cystic Dysplastic Kidney (MCDK) . . . . . . . . . . . . . . . . . . 173
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
5.2 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
5.3 Etiology and Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . 175
5.4 Histologic Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
5.5 The Natural History of Multicystic Dysplastic Kidney . . . . . 178
5.6 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
5.7 Associated Anomalies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
5.9 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
5.10 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
6 Congenital Ureteral Anomalies . . . . . . . . . . . . . . . . . . . . . . . . . . 187
6.1 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
6.4 Duplex (Duplicated) System . . . . . . . . . . . . . . . . . . . . . . . . . 189
6.4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
6.4.2 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
xii Contents

6.4.4 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
6.5 Ectopic Ureter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
6.5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
6.5.2 Embryology and Pathophysiology . . . . . . . . . . . . . . . 198
6.5.4 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
6.5.5 Surgical Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
6.6 Ureterocele . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
6.6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
6.6.2 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
6.6.4 Investigations and Diagnosis . . . . . . . . . . . . . . . . . . . 204
6.6.5 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
6.7 Vesicoureteral Reflux (VUR) . . . . . . . . . . . . . . . . . . . . . . . . . 208
6.8 Mega Ureter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
7 Congenital Megaureter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
7.2 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
7.3 Etiology and Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . 223
7.4 Clinical Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
7.6 Treatment and Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
7.7 Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
8 Vesicoureteral Reflux (VUR) in Children . . . . . . . . . . . . . . . . . . 237
8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
8.3 Classification of VUR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
8.4 Etiology of VUR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
8.6 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
8.7 Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
8.7.1 Medical Treatment of VUR . . . . . . . . . . . . . . . . . . . . 259
8.7.2 Antibiotics Used for Prophylaxis . . . . . . . . . . . . . . . . 261
8.7.3 Anticholinergics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
8.7.4 Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
8.8 Surgical Therapy of VUR . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
8.8.1 Indications for Surgical Interventions . . . . . . . . . . . . 262
8.8.2 Indications for Surgical Interventions
Based on Age at Diagnosis and the Presence
or Absence of Renal Lesions . . . . . . . . . . . . . . . . . . . 262
8.8.3 Endoscopic Injection . . . . . . . . . . . . . . . . . . . . . . . . . 263
8.8.4 Surgical Management . . . . . . . . . . . . . . . . . . . . . . . . 266
8.9 Mortality/Morbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
Contents xiii
9 Pediatric Urolithiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271

9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
9.2 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
9.3 Classification of Urolithiasis . . . . . . . . . . . . . . . . . . . . . . . . 278
9.4 Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 278
9.5 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
9.6 Complications of Urolithiasis . . . . . . . . . . . . . . . . . . . . . . . 282
9.7 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
10 Persistent Müllerian Duct Syndrome (PMDS) . . . . . . . . . . . . . . 287
10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
10.2 Embryology of Persistent Müllerian Duct Syndrome . . . . . 287
10.3 Etiology and Inheritance of PMDS . . . . . . . . . . . . . . . . . . . 290
10.4 Classification of PMDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
10.6 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
10.7 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
11 Neurogenic Bladder Sphincter Dysfunction . . . . . . . . . . . . . . . . 295
11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
11.2 Physiology and Bladder Function . . . . . . . . . . . . . . . . . . . . 296
11.2.1 Micturition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
11.3 Pathophysiological Changes of NBSD . . . . . . . . . . . . . . . . 301
11.4 Etiology and Clinical Features . . . . . . . . . . . . . . . . . . . . . . 302
11.5 Investigations and Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . 310
11.6 Classification of Neurogenic Bladder . . . . . . . . . . . . . . . . . 313
11.7 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
11.8 Clean Intermittent Catheterization . . . . . . . . . . . . . . . . . . . 316
11.9 Anticholinergics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
11.10 Botulinum Toxin Type A . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
11.11 Tricyclic Antidepressant Drugs . . . . . . . . . . . . . . . . . . . . . . 318
11.12 Surgical Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
12 Urinary Tract Infection in Infants and Children . . . . . . . . . . . . 323
12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
12.2 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
12.3 Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
12.5 Investigations and Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . 327
12.6 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
13 Bladder Exstrophy-Epispadias Complex . . . . . . . . . . . . . . . . . . 337
13.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
13.2 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
13.3 Epispadias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
13.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
13.3.2 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343
13.3.3 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344
xiv Contents
13.3.4 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345

13.3.5 Surgical Repair of Male Epispadias . . . . . . . . . . . . 347
13.3.6 Female Epispadias . . . . . . . . . . . . . . . . . . . . . . . . . 348
13.3.7 Surgical Repair of Female Epispadias . . . . . . . . . . 349
13.3.8 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
13.4 Bladder Exstrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
13.4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
13.4.2 Associated Anomalies . . . . . . . . . . . . . . . . . . . . . . . 354
13.4.3 Principles of Surgical Management
of Bladder Exstrophy . . . . . . . . . . . . . . . . . . . . . . . 355
13.4.4 Evaluation and Management. . . . . . . . . . . . . . . . . . 356
13.5 Cloacal Exstrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360
13.5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360
13.5.2 Skeletal Changes in Cloacal Exstrophy . . . . . . . . . 363
13.5.3 Etiology and Pathogenesis . . . . . . . . . . . . . . . . . . . 363
13.5.4 Prenatal Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . 364
13.5.5 Associated Anomalies . . . . . . . . . . . . . . . . . . . . . . . 364
13.5.6 Clinical Features and Management . . . . . . . . . . . . 366
13.5.7 Surgical Repair of Cloacal Exstrophy. . . . . . . . . . . 368
13.5.8 Surgical Reconstruction . . . . . . . . . . . . . . . . . . . . . 370
13.5.9 Management of Urinary Incontinence . . . . . . . . . . 371
13.5.10 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
13.5.11 Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
14 Megacystis Microcolon Intestinal Hypoperistalsis
Syndrome (Berdon Syndrome) . . . . . . . . . . . . . . . . . . . . . . . . . . 373
14.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
14.2 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374
14.5 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
14.6 Treatment and Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
15 Cloacal Anomalies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
15.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
15.3 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384
15.5 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
15.6 Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391
16 Urachal Remnants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
16.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
16.2 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
16.3 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
Contents xv

16.5 Tumors and Urachal Remnants . . . . . . . . . . . . . . . . . . . . . 398
16.6 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400
17 Inguinal Hernias and Hydroceles . . . . . . . . . . . . . . . . . . . . . . . . 401
17.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
17.2 Inguinal Hernia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
17.2.1 Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
17.2.2 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402
17.2.3 Clinical Features. . . . . . . . . . . . . . . . . . . . . . . . . 403
17.2.4 Variants of Hernia . . . . . . . . . . . . . . . . . . . . . . . 404
17.2.5 Complications of Inguinal Hernias . . . . . . . . . . 406
17.2.6 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
17.2.7 Complications of Inguinal Herniotomy . . . . . . . 410
17.3 Hydrocele . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
17.3.1 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
17.3.2 Classification of Hydroceles . . . . . . . . . . . . . . . 411
17.3.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414
18 Cloacal Exstrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
18.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
18.2 Etiology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . 415
18.3 Associated Anomalies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417
18.4 Clinical Features and Management . . . . . . . . . . . . . . . . . . 418
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
19 Posterior Urethral Valve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
19.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
19.2 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 424
19.4 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 426
19.6 Investigations and Diagnosis . . . . . . . . . . . . . . . . . . . . . . . 428
19.7 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433
19.8 Medications Used in Patients with PUV . . . . . . . . . . . . . . 437
19.9 Prognosis and Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . . . 438
19.10 Long-Term Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439
19.10.1 Vesico-ureteric Reflux . . . . . . . . . . . . . . . . . . . . 440
19.10.2 Hydro-ureteronephrosis . . . . . . . . . . . . . . . . . . . 440
19.10.3 Bladder Dysfunction . . . . . . . . . . . . . . . . . . . . . 441
19.10.4 Renal Transplantation. . . . . . . . . . . . . . . . . . . . . 441
19.10.5 Fertility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
20 Utricular Cyst (Prostatic Utricular Cyst) . . . . . . . . . . . . . . . . . . 443
20.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443
20.2 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
20.3 Classification of Utricular Cysts . . . . . . . . . . . . . . . . . . . . . 445
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20.5 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446
20.6 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447
20.7 The Müllerian Duct Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . 448
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
21 Hypospadias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451
21.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451
21.2 Effects of Hypospadias . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455
21.3 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455
21.4 Etiology of Hypospadias . . . . . . . . . . . . . . . . . . . . . . . . . . 456
21.6 Classification of Hypospadias . . . . . . . . . . . . . . . . . . . . . . 458
21.7 Clinical Features of Hypospadias . . . . . . . . . . . . . . . . . . . . 462
21.8 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464
21.9 Urinary Diversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472
21.10 Postoperative Complications . . . . . . . . . . . . . . . . . . . . . . . 473
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 476
22 Male Circumcision . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
22.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
22.2 Anatomy and Pathophysiology . . . . . . . . . . . . . . . . . . . . . . 479
22.3 History of Circumcision . . . . . . . . . . . . . . . . . . . . . . . . . . . 480
22.4 Pain Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 482
22.5 Indications for Circumcision . . . . . . . . . . . . . . . . . . . . . . . 482
22.6 Contraindications to Circumcision . . . . . . . . . . . . . . . . . . . 485
22.7 Surgical Procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 486
22.8 Complications of Circumcision . . . . . . . . . . . . . . . . . . . . . 492
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
23 Priapism in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 501
23.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 501
23.3 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505
23.4 Classification of Priapism . . . . . . . . . . . . . . . . . . . . . . . . . . 507
23.6 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509
23.7 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 510
23.8 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 512
23.9 Priapism and Sickle Cell Disease . . . . . . . . . . . . . . . . . . . . 513
23.9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 513
23.9.2 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514
23.9.3 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514
23.9.4 Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . 515
23.9.5 Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . 517
23.9.6 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519
23.9.7 Prevention of Stuttering Priapism. . . . . . . . . . . . . 521
23.9.8 Complications of Priapism and Prognosis . . . . . . 524
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 524
Contents xvii
24 Undescended Testes (Cryptorchidism) . . . . . . . . . . . . . . . . . . . . 527

24.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 527
24.2 Embryology and Normal Testicular Development
and Descent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
24.3 Classification of Undescended Testes. . . . . . . . . . . . . . . . . 531
24.4 Causes of Undescended Testes and Risk Factors . . . . . . . . 531
24.5 Histopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532
24.6 Classification of Abnormal Testes . . . . . . . . . . . . . . . . . . . 533
24.7 Clinical Features and Diagnosis . . . . . . . . . . . . . . . . . . . . . 537
24.8 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 538
24.8.1 Success of Surgical Treatment . . . . . . . . . . . . . . . 541
24.9 Complications of Orchidopexy. . . . . . . . . . . . . . . . . . . . . . 541
24.10 Infertility and Undescended Testes. . . . . . . . . . . . . . . . . . . 541
24.11 Undescended Testes and the Risk of Cancer . . . . . . . . . . . 542
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 543
25 Varicocele . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545
25.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 545
25.2 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 546
25.4 Grading of Varicoceles . . . . . . . . . . . . . . . . . . . . . . . . . . . . 547
25.6 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548
25.7 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549
25.8 Postoperative Complications . . . . . . . . . . . . . . . . . . . . . . . 550
25.9 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551
26 Testicular Torsion and Torsion of the Testicular
or Epididymal Appendage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553
26.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553
26.2 Etiology and Risk Factors. . . . . . . . . . . . . . . . . . . . . . . . . . 554
26.3 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 555
26.4 Intermittent Testicular Torsion . . . . . . . . . . . . . . . . . . . . . . 556
26.5 Classification of Testicular Torsion . . . . . . . . . . . . . . . . . . 556
26.6 Effects of Testicular Torsion . . . . . . . . . . . . . . . . . . . . . . . . 557
26.8 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 560
26.9 Intra-uterine Torsion of Testes . . . . . . . . . . . . . . . . . . . . . . 562
26.9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562
26.9.2 Etiology of Extravaginal Torsion . . . . . . . . . . . . . 562
26.9.4 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563
26.10 Torsion of the Testicular or Epididymal Appendage . . . . . 565
26.10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565
26.10.2 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 567
26.10.4 Investigations and Treatment . . . . . . . . . . . . . . . . 567
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 568
xviii Contents
27 Testicular Tumors in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . 569

27.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 569
27.2 Classification of Testicular Tumors . . . . . . . . . . . . . . . . . . 573
27.3 Histologic Classification of Seminomas . . . . . . . . . . . . . . . 576
27.4 Etiology of Testicular Tumors . . . . . . . . . . . . . . . . . . . . . . 576
27.6 Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 580
27.6.1 Regional Lymph Node Staging. . . . . . . . . . . . . . . 581
27.7 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582
27.8 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
27.9 Yolk Sac Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 585
27.10 Teratoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 586
27.11 Mixed Germ Cell Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . 587
27.12 Stromal Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 587
27.13 Simple Testicular Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589
27.14 Epidermoid Cysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589
27.15 Testicular Microlithiasis (TM) . . . . . . . . . . . . . . . . . . . . . . 589
27.16 Gonadoblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 590
27.17 Cystic Dysplasia of the Testes . . . . . . . . . . . . . . . . . . . . . . 590
27.18 Leukemia and Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . 590
27.19 Paratesticular Rhabdomyosarcoma. . . . . . . . . . . . . . . . . . . 591
27.20 Prognosis and Outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . 592
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 592
28 Splenogonadal Fusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595
28.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595
28.2 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 596
28.3 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 596
28.6 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 598
28.7 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 598
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 599
29 Acute Scrotum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601
29.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601
29.2 Torsion of Testes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601
29.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601
29.2.2 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . 602
29.2.3 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 603
29.2.5 Effects of Torsion of Testes . . . . . . . . . . . . . . . . . 605
29.2.6 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . 606
29.2.7 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 606
29.3 Torsion of the Testicular or Epididymal Appendage . . . . . 608
29.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
29.3.2 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609
Contents xix
29.4 Epididymitis, Orchitis, and Epididymo-orchitis . . . . . . . . . 610

29.4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 610
29.4.2 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 610
29.5 Idiopathic Scrotal Edema . . . . . . . . . . . . . . . . . . . . . . . . . . 612
29.6 Testicular Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 613
29.7 Other Causes of Acute Scrotum . . . . . . . . . . . . . . . . . . . . . 613
29.8 Splenogonadal Fusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 614
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 617
30 Hydrocolpos, Vaginal Agenesis and Atresia . . . . . . . . . . . . . . . . 619
30.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 619
30.2 Imperforate Hymen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 619
30.3 Vaginal Atresia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 621
30.4 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 621
30.6 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 622
30.8 Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 625
30.9 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 628
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 633
31 Disorders of Sexual Development . . . . . . . . . . . . . . . . . . . . . . . . 635
31.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635
31.2 Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 639
31.3 Sexual and Gonadal Differentiation . . . . . . . . . . . . . . . . . . 642
31.4 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645
31.5 Evaluation of a Newborn with DSD . . . . . . . . . . . . . . . . . . 651
31.6 Diagnosis and Investigations . . . . . . . . . . . . . . . . . . . . . . . 653
31.7 Management of Patients with DSD . . . . . . . . . . . . . . . . . . 656
31.8 Surgical Corrections of DSD . . . . . . . . . . . . . . . . . . . . . . . 657
31.9 Congenital Adrenal Hyperplasia (CAH) . . . . . . . . . . . . . . 659
31.10 Androgen Insensitivity Syndrome
(Testicular Feminization Syndrome) . . . . . . . . . . . . . . . . . 665
31.11 Deficiency of MIS (Persistent Müllerian Duct Syndrome) . . . 670
31.12 5-Alpha-Reductase Deficiency . . . . . . . . . . . . . . . . . . . . . . 672
31.13 Gonadal Dysgenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 673
31.14 Deficient Testosterone Biosynthesis . . . . . . . . . . . . . . . . . . 678
31.15 Ovotestis Disorders of Sexual Development . . . . . . . . . . . 679
31.16 Other Rare Disorders of Sexual Development . . . . . . . . . . 682
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 687
Congenital Urological
Malformations 1
1.1 Introduction • They are responsible for 34–59 % of chronic

kidney disease (CKD) and for 31 % of all
• The urinary system is comprised of two cases of end-stage kidney disease (ESKD) in
kidneys, two ureters, a bladder and a urethra. children.
• The kidneys contains the nephrons which are • Congenital anomalies of the kidney and uri-
responsible to filter the blood as it passes nary tract comprise a wide range of structural
through the kidney. and functional malformations that occur at the
• It is estimated that the kidneys will filter level of:
around 190 l of water every day from the – The kidney
blood. Most of the water from the blood that is – Collecting system
filtered is reabsorbed into the body and the – Bladder
remaining water is excreted as urine. – Urethra
• This water travels down the ureters to the blad- • With improved prenatal screening, many cases
der which acts as a storage area for the urine. of CAKUT are diagnosed by antenatal ultra-
• When the bladder reaches a certain volume, sonography performed on 18–20 weeks of
nerves in the walls of the bladder are stimu- gestation.
lated and urination happens. • Most common antenatal manifestations of
• The kidneys also play an important role in red CAKUT include oligohydramnios or
blood cell production. Erythropoietin, which variations in gross morphology of the kidney,
is produced in the kidneys stimulates the pro- ureter, or bladder.
duction of the red blood cells. • CAKUTs anomalies can be:
• Congenital anomalies of the kidney and uri- – Sporadic
nary tract (CAKUT) are common in children. – Familial
• They represent approximately 30 % of all pre- – Syndromic
natally diagnosed malformations. – Nonsyndromic
• Congenital anomalies of the kidney and uri- • Syndromic CAKUTs:
nary tract occur in 3–6 per 1,000 live births. – They develop in association with other
• They account for the most cases of pediatric additional congenital abnormalities outside
end-stage kidney disease (ESKD), and predis- of the kidney and urinary tract.
pose an individual to hypertension and cardio- – They manifest clinically recognizable fea-
vascular disease throughout life. tures of a known syndrome.
© Springer International Publishing Switzerland 2017 1

A.H. Al-Salem, An Illustrated Guide to Pediatric Urology, DOI 10.1007/978-3-319-44182-5_1
2 1 Congenital Urological Malformations
• Nonsyndromic CAKUT: form the urogenital sinus and anal canal,

– Congenital structural anomalies confined respectively.
only to the kidney and urinary tract. • The urogenital sinus further differentiates into
• Genetic causes have been identified in associ- three anatomic components:
ation with the syndromic forms of congenital – The vesical (cranial) portion
malformations. – The pelvic (middle) portion
• The spectrum of congenital anomalies includes – The phallic (caudal) portion
more common anomalies such as vesicoure- • The pelvic and phallic portions will form the
teral reflux and, rarely, more severe malforma- urethra and genitals, respectively.
tions such as bilateral renal agenesis. • The vesical portion forms most of the bladder
• These congenital anomalies can be unilateral and is continuous with the allantois.
or bilateral, and sometimes different defects • The allantois normally constricts to a thick
coexist in the same child. fibrous cord, the median umbilical ligament,
• It is important to recognize and diagnose these and extends from the apex of the bladder to
anomalies early as early treatment will mini- the umbilicus.
mize renal damage, prevent or delay the onset • The trigone portion of the bladder is formed
of ESRD, and provide supportive care to avoid from the caudal ends of the mesonephric
complications of ESRD. ducts, which are incorporated into the devel-
oping bladder wall.
• The ureters are formed from the ureteral buds.
1.2 Normal Embryology • The ureteral bud is an outgrowth of the meso-
nephric duct near its entrance into the cloaca.
• The two most common congenital bladder This will elongate and develop into the ureter.
abnormalities are: • The more distal ureteral bud undergoes a com-
– Bladder exstrophy plex interaction with the primitive kidney to
– Congenital diverticula induce differentiation of the renal parenchyma
• An exstrophic bladder is one that is open to and formation of the renal pelvis, calyces, and
the outside and turned inside out, so that its collecting tubules.
inside is visible at birth, protruding from the • As the kidneys develop and ascend, traction
lower abdomen. on the ureters causes the ureteral orifices to
• A diverticulum is an extension of a hollow move superolaterally, resulting in an oblique
organ, usually shaped like a pouch with a nar- course through the muscular wall at the base
row opening. of the bladder.
• The terminal portion of the hindgut is called • The kidneys are paired organs located retro-
the cloaca. peritoneally. Their vascular supply comes
• The cloaca forms the future urinary and gas- from the renal arteries, and they drain into the
trointestinal tracts. renal veins. Each kidney excretes into a ureter,
• The cloaca is formed early in fetal life by which will in turn empty into the urinary blad-
incorporation of the allantois to form a com- der. Its functional unit is the nephron.
mon distal channel for the primitive urinary • The urogenital system arises from intermedi-
and gastrointestinal systems. ate mesoderm which forms a urogenital ridge
• The most caudal portion of the cloaca is the on either side of the aorta.
cloacal membrane. • The urogenital ridge develops into three sets
• This separates the cloaca from the amniotic of tubular nephric structures (from head to
cavity. tail): the pronephros, the mesonephros, and
• During the fourth to seventh weeks of devel- the metanephros.
opment, the cloaca is divided by the urorectal • During the development of the kidney, there
septum into anterior and posterior portions to are three main structures initially, which
1.2 Normal Embryology 3
derive from intermediate mesoderm. These – Together this will lead to the formation of a
structures are pronephros, mesonephros and renal corpuscle allowing for filtration of
metanephros. blood.
• The development of the kidney proceeds – Laterally, the tubule enters the mesoneph-
through a series of three successive phases, ric collecting duct (wolffian duct).
each marked by the development of a more – This filtrate flows through the mesonephric
advanced kidney: tubule and is drained into the continuation
– The pronephros of the pronephric duct, now called the
– The mesonephros mesonephric duct or Wolffian duct.
– The metanephros – The nephrotomes of the pronephros degen-
• The pronephros: erate while the mesonephric duct extends
– This is the most immature form of the towards the most caudal end of the embryo,
kidney. ultimately attaching to the cloaca.
– During approximately day 22 (fourth – These mesonephric tubules carry out some
embryonic week) of human gestation, the kidney function at first, but then many of
paired pronephros appear towards the cra- the tubules regress. However, the meso-
nial end of the intermediate mesoderm. nephric duct persists and opens to the clo-
– It develop as a condensation of intermedi- aca at the tail of the embryo.
ate mesoderm in the lower cervical and – In both sexes, the ureters, renal pelvis, and
upper thoracic regions extending to the clo- bladder trigone are derived from the meso-
aca, and almost entirely regresses in gesta- nephric duct.
tional week 4. – In males, the mesonephric duct also gives
– It appears as seven to ten cell groups and rise to the vasa deferentia, epididymides,
arrange themselves in a series of tubules and seminal vesicles; the former is part of
called nephrotomes and join laterally with the duct itself, while the latter two struc-
the pronephric duct. tures arise as a result of ductal dilatation or
– The pronephric duct, which arises from outpouching.
dorsal and caudal evaginations of the pro- – Once the mesonephric duct comes in con-
nephros, is preserved and ultimately will tact with the cloaca at the caudal aspect of
give rise to the mesonephric duct. the embryo, it then grows cranially as the
• The mesonephros: ureteric bud until it comes in contact with
– The mesonephros begins to develop as the the metanephric mesenchyme, forming the
pronephros is regressing (fourth week). metanephros.
– The development of the pronephric duct – The ureteric bud and metanephric mesen-
proceeds in a cranial-to-caudal direction. chyme reciprocally induce growth, form-
– As it elongates caudally, the pronephric ing the kidney.
duct induces nearby intermediate meso- • The metanephros:
derm in the thoracolumbar area to become – This gives rise to the definitive kidney.
epithelial tubules called mesonephric – The metanephros develops from several
tubules. components:
– It starts as a series of S-shaped tubules. • An outgrowth of the caudal mesoneph-
– Each mesonephric tubule receives a blood ric duct
supply from a branch of the aorta, ending • The ureteric bud
in a capillary tuft analogous to the glomer- • A condensation of nearby renogenic
ulus of the definitive nephron. intermediate mesoderm, the metaneph-
– The tubules around the glomerulus will ric blastema
form a Bowmann’s capsule around the cap- – The metanephros appears during the fifth
illary tuft. week of intrauterine life.
– The kidney has two parts: • The vesical epithelium is entirely derived from
• The collecting system the endodermal layer of the urogenital sinus.
• The excretory system • The mesonephric duct gives rise to the ureter.
– The collecting system develops from the • With continued caudal growth of the embryo,
ureteric bud which is an outgrowth of the the proximal end of the mesonephric duct is
mesonephric duct. progressively absorbed caudally and the com-
• The ureteric bud penetrates the meta- mon portion of the mesonephric duct is
nephric tissue. absorbed into the bladder trigone and urogeni-
• The bud then dilates, forming a renal tal sinus.
pelvis. • The discrete branches of the mesonephric duct
• The renal pelvis will differentiate into which will become the male genital ducts and
the major calyces. ureters becomes distinct entities attached to
• The major calyces will further differen- the urogenital sinus.
tiate and subdivide for 12 or more gen- • The nonepithelial layers of the detrusor (non-
erations to form the minor calyces. trigone) portion of the bladder arise from con-
• By the fifth generation, the renal pyra- densations of splanchnic mesenchyme.
mids are formed. • The lumen of the allantois, which connects the
– The excretory system is formed because a bladder and the anterior abdominal wall,
metanephric tissue cap is induced by the closes over time, yielding the urachus. Over
collecting tubules to form renal vesicles. time, the urachus becomes more fibrotic and
– The vesicles form an s-shaped tubules becomes the median umbilical ligament.
which is covered in capillaries, giving rise • The prostate gland develops around 9–11 ges-
to glomeruli. tational weeks from the urogenital sinus, as
– The tubules and the glomeruli form the endoderm invaginates into surrounding
nephron. mesenchyme.
– Continues expansion of the tubules will • Prostate development is an androgen-
form the convoluted tubules of the kidney dependent process.
and the loop of Henle. • It appears that the mesenchyme, rather than the
– At birth, approximately 750,000–1 million endoderm, must be androgen-sensitive in order
nephrons are present in each kidney; postna- for normal prostatic development to occur.
tally, renal size may increase, owing to elon- • The urethra develops from the urogenital
gation of the proximal convoluted tubules. sinus, with endoderm giving rise to the epithe-
– With differential longitudinal growth of the lium and splanchnic mesenchyme giving rise
embryo, the kidney ascends from its initial to the surrounding soft tissue.
location in the pelvis to its final location in • In males, the most distal part of the urethra
the upper retroperitoneum. (the glanular portion) appears to arise from an
– During ascent, transient blood vessels seri- ectodermal invagination which then joins with
ally arise and degenerate; these arteries the endodermal epithelium of the proximal
persist in ectopic kidneys as well as in urethra to create a continuous channel.
some orthotopic renal units.
– Concurrently, the kidneys rotate around
their vertical and horizontal axes so that 1.3 Abnormalities of the Kidney
their final orientation is one in which the
upper poles are slightly more medial and • Normal renal development depends upon the
anterior than the lower poles. interaction between the ureteric bud and meta-
• The urogenital sinus can be further subdivided nephric mesenchyme, which induces organo-
into cranial (future bladder) and caudal (future genesis resulting in the formation of the
prostate, urethra, and external genitalia) 600,000–2 million nephrons and the collect-
portions. ing system of each kidney.
1.3 Abnormalities of the Kidney 5
• The kidney is the most common site of con- • The male to female ratio is around 1.2:1.
genital abnormalities. • Approximately 56 % of unilateral renal agen-
• Renal malformations are often associated with esis occurs on the left side.
other congenital defects such as a grossly • Most patients with unilateral renal agenesis
deformed pinna with ipsilateral abnormalities are asymptomatic if the other kidney is fully
of the facial bones. functional.
• However, hypertension, proteinuria and renal
failure may develop in the long term follow-
1.3.1 Renal Agenesis ups (20–50 % of cases at the age of 30), which
may be based on glomerular hyperfiltration.
• Renal agenesis is a congenital malformation • Due to this increased risk of hypertension and/
in which one (unilateral) or both (bilateral) or proteinuria, long-term follow-up of these
fetal kidneys fail to develop. patients is important.
• Renal agenesis can be unilateral or bilateral • Associated malformations:
but almost always unilateral. – Unilateral renal agenesis may be an iso-
• Unilateral renal agenesis is a relatively com- lated congenital malformation or may be
mon congenital urinary malformation. associated with chromosomal abnormali-
• It is usually diagnosed during fetal ultraso- ties or a variety of nonchromosomal
nography or incidentally on ultrasound done syndromes including the VACTERL and
for other reasons. MURCS associations.
• Some cases of unilateral renal agenesis may – Congenital cardiac malformations are the
represent involution of a previous multicystic most common malformations associated
disease of the kidney (Figs. 1.1, 1.2, and 1.3). with unilateral renal agenesis.
• Up to 40 % of women with a urogenital tract – Girls with unilateral renal agenesis should
anomaly also have an associated renal tract have a pelvic ultrasound to look for abnor-
anomaly. malities in the müllerian structures.
• Adults with unilateral renal agenesis have – Vesicoureteral reflux is the most common
considerably higher chances of hypertension. abnormality noted in the contralateral
• The annual incidence of unilateral renal agen- kidney.
esis is estimated at around 1 in 2,000 live – It is associated with an increased incidence
newborns. of Müllerian duct abnormalities, and can
Figs. 1.1 and 1.2 Abdominal ultrasound showing left atrophic kidney. This is most likely following involution of a
previous multicystic kidney
an empty renal fossa, followed by renography

ATROPHIC KIDNEY
to confirm the presence of a solitary function-
ing kidney.
URETEROCELE
• The size of the solitary functioning kidney is
DILATED increased in the majority of patients.
URETER
• A voiding cystourethrogram should be consid-
ered in order to detect vesicoureteral reflux
(VUR).
Fig. 1.3 Intraoperative photograph showing a very small
atrophic kidney. Note also the massively dilated ureter • The differential diagnoses include:
secondary to an obstructive ureterocele – Extreme unilateral renal dysplasia
– Involuted multicystic dysplastic kidney
– Renal ectopia
be a cause of infertility, hematocolpos, • In most familial cases, unilateral renal agene-
increased need for Caesarean sections, or sis is inherited in an autosomal dominant man-
other problems. ner with incomplete penetrance.
– Herlyn-Werner-Wunderlich syndrome is • Unilateral renal agenesis can occur with dys-
one such syndrome in which unilateral plasia or hypoplasia of the solitary function-
renal agenesis is combined with a blind ing kidney which makes the prognosis more
hemivagina and uterus didelphys. serious.
– Renal agenesis is occasionally associated
with genital tract anomalies on the same
side such as seminal vesicle hypoplasia and 1.3.2 Renal Hypoplasia
absence of the vas deferens.
– Other anomalies occur in up to 40 % of • Renal hypoplasia is a common congenital
patients, mainly cardiac (such as atrial or malformations.
ventricular septal defects) and gastrointes- • It is poorly understood and commonly used to
tinal (such as anorectal agenesis). describe a congenitally small kidneys with a
• Renal agenesis results from a development reduced number of nephrons but normal
failure of the ureteric bud and the metanephric architecture.
mesenchyme. • There are however two distinct conditions:
• Unilateral renal agenesis can be caused by – Oligomeganephronia:
mutations in many genes, such as RET • This is a type of renal hypoplasia that
(10q11.2), BMP4 (14q22-23), FRAS1 results from a quantitative defect of the
(4q21.21), FREM1 (9p22.3 or UPK3A renal parenchyma with a reduced num-
(22q13.31), PAX2 (10q24.31), HNF1B (17q12), ber of nephrons.
DSTYK (1q32). – Simple renal hypoplasia:
• Unilateral renal agenesis can occur as part of • This is characterized by reduction in the
multi-organ syndromes, several of which have renal mass but the number of nephrons
defined genetic bases, including Kallmann syn- is normal.
drome, branchio-oto-renal syndrome, diGeorge • It was estimated that renal hypoplasia affect
syndrome, Fraser syndrome, MURCS associa- about 2.2 % of the population.
tion, Poland syndrome, renal cysts and diabetes • The exact incidence of renal hypoplasia is not
syndrome, and Williams-Beuren syndrome. known but it is estimated to occur 1 in 400 live
• Maternal diabetes mellitus or use of specific births.
drugs during pregnancy can also result in renal • This however is not a true incidence of pure
agenesis. renal hypoplasia because the majority of con-
• Prenatal suspicion of unilateral renal agenesis genitally small kidneys also exhibit evidence
is confirmed by postnatal ultrasound showing of renal dysplasia.
• Severe bilateral reductions in nephron num- • In some cases the separation of the redupli-
bers that are characteristic of renal hypoplasia/ cated organ is incomplete forming fused
dysplasia are the leading cause of childhood supernumerary kidney.
end stage renal disease. • Associated anomalies:
• A much less reduction in nephron number – Urogenital anomalies such as fusion anom-
caused by mild bilateral renal hypoplasia, alies, ectopic ureteric opening, vaginal and
have been associated with the development of uretral atresia, urethral or penile
adult-onset hypertension and chronic renal duplication.
failure. – Non-urogenital anomalies such as coarcta-
• The diagnosis of hypertension in patients with tion of aorta, imperforate anus, ventricular
unilateral hypoplasia/dysplasia is an indica- septal defect and meningomyelocele.
tion for nephrectomy. • Supernumerary kidneys are most commonly
• Oligomeganephronia: located on the left side of the abdomen.
– This results from arrested development of • A supernumerary kidney may be of same size
the metanephric blastema at 14–20 weeks’ as, larger than, or more commonly smaller
gestation, with subsequent hypertrophy of than the usual kidney.
glomeruli and tubules in the kidney. • It functions normally, possess a normal shape
– This hypertrophy and hyperfiltration results and capsule, and is either not attached to or
in further nephron injury and sclerosis. loosely attached to the normal kidney but in an
Eventually, this progressive loss of nephrons abnormal location.
leads to end-stage renal disease (ESRD). • A supernumerary kidney may be located in
– Oligomeganephronia is usually found in front, below, above, or behind the normal kid-
infants in their first year of life and presents ney. They can also be found in the iliac region
with anorexia, vomiting, and failure to thrive. or anterior to the sacral promontory.
– After the first year of life, individuals with • The supernumerary kidney is thought to be an
oligomeganephronia most often present accessory organ with a separate arterial sup-
with short stature, polyuria and polydipsia, ply, venous drainage, collecting system, and
or proteinuria. distinct encapsulated tissue.
• It may have either a separate ureter or more
commonly bifid ureters (50 %). Rarely the
1.3.3 Supernumerary Kidneys ureter of the supernumerary kidney may have
an ectopic opening.
• Supernumerary kidneys are a rare congenital • Symptoms have been noted in approximately
anomaly of the urogenital system, where there two-thirds of the reported cases of supernu-
are one or two accessory kidneys. merary kidney. When symptomatic they may
• A third kidney may be confused with the rela- cause fever, pain, or palpable abdominal mass.
tively common unilateral duplication of the • The diagnosis of supernumerary kidney can
renal pelvis. be made by:
• Supernumerary kidney results from the aber- – IVU
rant division and splitting of the nephrogenic – Ultrasonography
blastema into two metanephric blastemas or – Nuclear scintigraphy
from separate metanephric blastemas into – CT
which partially or completely reduplicated – MRI
ureteral stalks enter to form separate capsu- • Bilateral supernumerary kidney is extremely
lated kidneys. rare.
• The end result is two kidneys in association • Surgery is indicated when supernumerary kid-
with a partially or completely duplicated ure- neys are affected by pathologic conditions and
teral bud. become symptomatic
1.3.4 Renal Dysplasia der in which abnormal cysts develop and grow
and Multicystic Kidney in the kidneys.
(Figs. 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, • It is characterized by multiple cysts typically
1.10, 1.11, and 1.12) involving both kidneys.
• About 15–17 % of cases initially present with
• Renal dysplasia is characterized by the pres- multiple cysts in one kidney, progressing to
ence of malformed renal tissue elements, bilateral disease in the majority.
including primitive tubules, interstitial fibro- • Polycystic kidney disease is one of the most
sis, and/or the presence of cartilage in the common hereditary diseases.
renal parenchyma. • It is the cause of nearly 10 % of end-stage renal
• Multicystic dysplastic kidney (MCDK), a disease and affects males, and females equally.
variant of renal dysplasia, is one of the most • Signs and symptoms of polycystic disease
frequently identified congenital anomalies of include:
the urinary tract. – High blood pressure
• Other terms used to describe this condition – Headaches
include multicystic kidney and multicystic – Abdominal pain
renal dysplasia. – Hematuria
• Multicystic kidney of the newborn is normally – Polyuria
seen in only one kidney as an irregularly lobu- – Pain in the back
lated mass of cysts and usually absent or • There are two types of polycystic kidney
atretic ureter. disease:
• Multicystic dysplastic kidney is the most com- – Autosomal dominant polycystic kidney
mon cause of an abdominal mass in the disease (ADPKD)
newborn and is the most common cystic mal- – Autosomal recessive polycystic kidney dis-
formation of the kidney in infancy. ease (ARPKD)
• Renal dysplasia is considered the leading • Autosomal dominant polycystic kidney dis-
cause of end-stage renal disease in children. ease (ADPKD):
• Multicystic dysplastic kidney is characterized – This is the most common of all the inher-
by: ited cystic kidney diseases
– The presence of multiple, noncommunicat- – The incidence is 1:500 live births
ing cysts of varying size separated by dys- – It is estimated that about 10 % of end-stage
plastic parenchyma and the absence of a kidney disease (ESKD) patients being
normal pelvocaliceal system. treated with dialysis were initially diag-
– It is associated with ureteral or ureteropel- nosed and treated for ADPKD.
vic atresia • There are three genetic mutations with similar
– The affected kidney is nonfunctional phenotypical presentation:
– Frequently, it is associated with contralat- – PKD-1
eral abnormalities, especially ureteropelvic – PKD-2
junction obstruction. – PKD3
• Dysplasia of the renal parenchyma is seen • Gene PKD1 is located on chromosome 16 and
with urethral obstruction or reflux present codes for a protein involved in regulation of
early in pregnancy, or obstructed ureter. cell cycle and intracellular calcium transport
in epithelial cells.
• Gene PKD1 is responsible for 85 % of the
1.3.5 Polycystic Kidney Disease cases of ADPKD.
• Gene PKD2 is located on chromosome 4 and
• Polycystic kidney disease, also known as codes for a group of voltage-linked calcium
polycystic kidney syndrome is a genetic disor- channels.
Figs. 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.11, and different sizes and shapes of these cysts. Note also the
1.12 Abdominal CT-scans and intraoperative photo- total absence of the ureter is some of them while the ureter
graphs showing multicystic dysplastic kidneys. Note the is small atretic or underdeveloped
Figs. 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 1.10, 1.11, and 1.12 (continued)
• Gene PKD3 is recently discovered third gene. • It is typically diagnosed in the first few weeks
• It is estimated that less than 10 % of cases of after birth.
ADPKD appear in non-ADPKD families. • Unfortunately, the kidneys are often underde-
• Cyst formation begins in utero and as the cysts veloped resulting in a 30 % death rate in new-
accumulate fluid, they enlarge, separate borns with ARPKD.
entirely from the nephron, compress the • ADPKD individuals might have a normal life;
neighboring kidney parenchyma, and progres- conversely, ARPKD can cause kidney dys-
sively compromise kidney function. function and can lead to kidney failure by the
age of 40–60.
1.3.5.1 Autosomal Recessive Polycystic • ADPKD1 and ADPKD2 are very different, in
Kidney Disease (ARPKD) that ADPKD2 is much milder.
• This is the lesser common of the two types of • Currently, there are no therapies proven effec-
PKD, with an incidence of 1:20,000 live tive to prevent the progression polycystic kid-
births. ney disease (autosomal dominant).
1.3.6 Simple (Solitary) Renal Cyst • Calcifications may be present; these

may be thick and nodular. There are no
• Numerous renal cysts are seen in the cystic enhancing soft tissue components.
kidney diseases, which include polycystic kid- • This also includes nonenhancing high-
ney disease and medullary sponge kidney. attenuation lesions that are completely
• Simple renal cysts are different from these contained within the kidney and are
cysts. 3 cm or larger.
• A renal cyst is an abnormal fluid collection in – Category III:
the kidney. • Indeterminate cystic masses with thick-
• Simple kidney cysts do not enlarge the kid- ened irregular septa with enhancement.
neys, replace their normal structure, or cause • 50 % of these lesions are ultimately
reduced kidney function like PKD. found to be malignant.
• Significant renal damage is rare in these cysts – Category IV:
and usually only requires continuous follow- • Malignant cystic masses with all the
up and no surgical interventions. characteristics of category III lesions
• There are several types of renal cysts based on but also with enhancing soft tissue com-
the Bosniak classification. ponents independent of but adjacent to
• The Bosniak classification categorizes renal the septa.
cysts into five groups. • 100 % of these lesions are malignant.
– Category I: • The majority are benign, simple cysts that can
• Benign simple cyst with thin wall with- be monitored. However, some are cancerous
out septa, calcifications, or solid or are suspicious for cancer and these are
components. removed.
• It does not enhance with contrast, and • Simple renal cysts are more common as peo-
has a density equal to that of water. ple age. An estimated 25 % of people 40 years
– Category II: of age and 50 % of people 50 years of age have
• Benign cyst with a few thin septa, which simple kidney cysts.
may contain fine calcifications or a • The cause of simple kidney cysts is not fully
small segment of mildly thickened understood and several theories were
calcification. proposed.
• This includes homogenous, high- – Obstruction of tubules
attenuation lesions less than 3 cm with – Deficiency of blood supply to the kidneys
sharp margins but without may play a role.
enhancement. – Diverticula sacs that form on the tubules,
• Hyperdense cysts must be exophytic may detach and become simple kidney
with at least 75 % of its wall outside the cysts.
kidney to allow for appropriate assess- • Simple kidney cysts usually do not cause
ment of margins, otherwise they are cat- symptoms or negatively affect the kidneys.
egorized as IIF. • In some cases, however, pain can develop
– Category IIF: when cysts enlarge and press on other
• Up to 5 % of these cysts are malignant organs.
and as such they require follow-up • Most simple kidney cysts are found during
imaging, though there is no consensus imaging tests done for other reasons.
recommendation on the appropriate • Sometimes cysts become infected, causing
interval of follow up. fever, pain, and tenderness.
• Well marginated cysts with a number of • Some studies have found a relationship
thin septa, with or without mild enhance- between simple kidney cysts and high blood
ment or thickening of septa. pressure.
• When a cyst is found, the following imag- 1.3.7 Renal Fusion and Renal
ing tests can be used to differentiate Ectopia
between simple and complicated renal
cysts. • Renal ectopy and fusion are common congeni-
– Abdominal ultrasound tal anomalies of the kidney and urinary tract,
– CT-scan and result from disruption of the normal
– MRI embryologic migration of the kidneys.
• Simple renal cysts that do not cause any • Although children with these anomalies are
symptoms require no treatment and can be generally asymptomatic, some children develop
monitored with periodic ultrasounds. symptoms due to complications, such as infec-
• Symptomatic simple renal cysts can be treated tion, renal calculi, and urinary obstruction
with ultrasound guided sclerotherapy. (Figs. 1.13, 1.14, 1.15, 1.16, 1.17, and 1.18).
• Large symptomatic simple renal cysts can be • The most frequent abnormality seen is a
drained and deroofed laparoscopically. horseshoe kidney containing two excretory
• Parapelvic cysts: systems and two ureters.
– Parapelvic cysts originate from around the • They are usually asymptomatic but are prone
kidney at the adjacent renal parenchyma, to obstruction.
and plunge into the renal sinus.
• Peripelvic cysts:
– Peripelvic cysts are contained entirely 1.3.8 Horseshoe Kidney
within the renal sinus, possibly related to
dilated lymphatic channels. • A horseshoe kidney is formed by fusion across
– They can mimic hydronephrosis when the midline of two distinct functioning kid-
viewed on CT in absence of contrast. neys, one on each side of the midline.
Figs. 1.13 and 1.14 CT-urography showing bilateral duplex kidney with hydroueters. Note the associated hydrone-
phrosis and the massively dilated ureters
Figs. 1.15, 1.16, 1.17, and 1.18 CT-urography showing duplex kidneys with hydronephrosis and hydroureters
• They are connected by an isthmus of either • The ureter also has a higher insertion point
functioning renal parenchyma or fibrous tissue. into the renal pelvis than that of a normal
• In the vast majority of cases the fusion is kidney.
between the lower poles (90 %). • The blood supply to the horseshoe kidney is
• In the remainder the superior or both the supe- also different than most kidneys. There is actu-
rior or inferior poles are fused. This latter con- ally several different ways that it can receive its
figuration is referred to as a sigmoid kidney. supply. The blood supply could arise from the
– The kidneys develop in the pelvis and aorta, the iliac arteries and the inferior mesen-
migrate up to their final position in the ret- teric artery. And it could occur as one of these,
roperitoneal space in the lumbar region. or a combination of all of them. Although in
• Prior to their ascent, the renal capsule has not 65 % of the cases, the isthmus is supplied by
matured and the kidneys still lie within the single vessel from the aorta.
pelvis. • It has been estimated that 22–24.8 % of
• It is suggested that abnormal flexion or growth patients with horseshoe kidney also have a
of the developing spine and pelvic organs renal vein anomaly as well. The most common
brings the immature kidneys together for a of these is multiple right renal veins.
longer period than usual, leading to fusion of • The kidneys are joined by an isthmus which
the two renal elements and hence forming the links the lower poles in 95 % of cases and the
so-called horseshoe kidney. upper poles in 5 %.
• As this abnormal fusion occurs in the pelvis, • The isthmus may be fibrotic, dysplastic, or
the subsequent kidney cannot undergo normal normal renal parenchyma.
migration and rotation. • The position of the isthmus is variable.
• In the normal kidneys, the lower poles of the • The isthmus lies at level of L4 just below the
kidneys rotate laterally. However, with a origin of the inferior mesenteric artery (IMA)
horseshoe kidney, these poles remain medially in 40 %.
positioned. • The presence of the IMA may restrict further
• The horseshoe kidney cannot migrate to the ascent of the horseshoe during early
usual position because the fusion will not embryogenesis.
allow passage by the inferior mesenteric • In another 40 % the kidneys the isthmus is
artery. located in a normal anatomical position, whilst
• Horseshoed kidney is the most common type the kidneys lie lower in the pelvis in the
of fusion anomaly. remaining 20 %.
• For the most part, the horseshoe kidney func- • Malrotation of the kidneys is always present
tions as a normal kidney. Many times, kidney and is attributed to early fusion prior to normal
malformations are accompanied by lower uri- rotation.
nary tract anomalies as well. • The renal pelvices remain anterior, with the
• With horseshoe kidney, the kidneys can be ureters crossing the isthmus.
located anywhere along the normal embryo- • The blood supply to horseshoe kidneys is
logic ascent of the kidneys. extremely variable.
• In 90 % of cases, the fusion of the kidneys – Thirty percent have a normal anatomical
occurs in the lower poles. In this condition, pattern
both kidneys are malrotated and their lower – The remaining 70 % are supplied by a com-
poles are joined. bination of vessels entering from the aorta
• The collection system of a horseshoe kidney is or the renal, mesenteric, iliac, or sacral
usually deviated inwards at the lower poles arteries.
because of the fusion with the isthmus. – The isthmus frequently has separate blood
• The ureters arise from the kidneys anterior vessels that may occasionally represent the
rather than medially. entire renal blood supply.
• Horseshoe kidneys are susceptible to trauma – Ureteral duplication is reported to occur in

and are an independent risk factor for the 10 %
development of renal calculi and transitional – VUR is reported to occur in 10–80 %.
cell carcinoma of the renal pelvis. – Multicystic dysplasia and autosomal domi-
• Horseshoe kidneys are found in approximately nant polycystic kidney disease has also
1 in 400–500 adults. been reported.
• They are more frequently encountered in – Horseshoe kidney is present in 21 % of
males (M:F 2:1). patients with trisomy 18 and in 7 % in those
• The vast majority of cases are sporadic, except with Turner’s syndrome.
for those associated with genetic syndromes. – Abdominal aortic aneurysms have been
• Horseshoe kidneys are frequently associated reported later in life .
with both genitourinary and non-genitourinary – Hypospadias and cryptorchidism occurs in
malformations. 4 % of males and bicornate uterus or sep-
• Chromosomal/aneupliodic anomalies: tate vagina in 7 % of females.
– Down syndrome • Outcomes depend on associated urological
– Turner syndrome: up to 7 % have a horse- problems as horseshoe kidneys are usually
shoe kidney asymptomatic.
– Edward syndrome (trisomy 18): up to 20 % • PUJ obstruction occurs in 30 % and is more
have a horseshoe kidney often left-sided.
– Patau syndrome (trisomy 13) • Renal calculi occur in up to 20 % of horseshoe
• Non-aneupliodic anomalies kidneys.
– Ellis-van Creveld syndrome • Xanthogranulomatous pyelonephritis has
– Fanconi anaemia been reported but is rare.
– Goltz syndrome • There is an increased risk of malignancy in
– Kabuki syndrome horseshoe kidneys in childhood.
– Pallister-Hall syndrome – Wilms tumor occurs with a 1.5- to 8-fold
– VACTERL association increased risk and surgical management
• Horseshoe kidneys are asymptomatic and usu- can be challenging.
ally identified incidentally. – Renal cell carcinoma, transitional cell car-
• They are however prone to a number of com- cinoma, oncocytoma and carcinoid have all
plications including: been described.
– Hydronephrosis, secondary to pelviureteric • The diagnosis of horseshoe kidney can be
junction obstruction confirmed by ultrasound, intravenous urogra-
– Renal calculi phy and CT-scan/MRI.
– Increased susceptibility to trauma • Horseshoe kidneys in themselves do not
– Infection and pyeloureteritis cystica require any treatment, and patients have nor-
– Increased incidence of malignancy mal life expectancy.
• Wilms tumour • It is however important to recognize their
• Transitional cell carcinoma presence prior to abdominal surgery or renal
• Renal carcinoid intervention for one of their many
– Renovascular hypertension complications.
• Associated abnormalities:
– It has been reported that one third of
patients with horseshoe kidney have at
least one other abnormality. 1.3.9 Crossed Fused Renal Ectopia
– The most commonly affected systems are
the gastrointestinal, skeletal, cardiovascu- • The second most common fusion anomaly is
lar and central nervous system. crossed renal ectopia.
• Crossed fused renal ectopia refers to an anom- • The vascular supply of fused kidneys is
aly where the kidneys are fused and located on extremely variable. There may be anomalous
the same side of the midline. branches to both kidneys arising from the
• If during ascent, one kidney advances slightly aorta or common iliac artery.
ahead of the other, the inferior pole of one • Rarely the renal artery crosses the midline to
may come into contact with the superior pole supply the crossed kidney.
of the lower kidney and fuse, resulting in • Urinary drainage is usually by separate ureters
crossed fused renal ectopia. entering the bladder on either side of the
• The exact cause of this is not fully trigone.
understood. • Most crossed kidneys are asymptomatic and
– Some evidence supports that an abnor- remain undetected throughout life.
mally situated umbilical artery prevents • However they may present with infection, a
normal cephalic migration. mass or on screening for urinary abnormali-
– Another theory is that the ureteric bud ties .
crosses to the opposite side and induces • More than 90 % of crossed renal ectopia
nephron formation in the contralateral results in renal fusion.
metanephric blastema. The result is a single • Subtypes:
renal mass with two collecting systems – Type a: inferior crossed fusion
being located on one side of the abdomen. – Type b: sigmoid kidney
• The estimated incidence is around 1 out of – Type c: lump kidney
7,000 births. – Type d: disc kidney
• It is more common in males than females with – Type e: L-shaped kidney
a M:F ratio of 2:1 . – Type f: superiorly crossed fused
• In crossed renal ectopia, both kidneys are • Crossed fused renal ectopia is more common
located on the same side and may occur with: on the left side (Left-to-right ectopy is 3:1).
– Fusion (85 %) • In 90 % of crossed ectopy, there is at least par-
– Without fusion (<10 %) tial fusion of the kidneys (the remainder
– Extremely rare it can be solitary or demonstrate two discrete kidneys on the same
bilateral side, crossed-unfused ectopy).
– The left kidney is three times more likely to • In a crossed fused renal ectopic kidney, com-
migrate to the right than vice versa. plications such as nephrolithiasis, infection,
– Other fusion anomalies are extremely rare and hydronephrosis approaches 50 %.
and include lump kidney, sigmoid kidney, • Crossed fused renal ectopia usually doesn’t
disk kidney and L-shaped kidney. require any primary treatment.
– There are rare cases of familial crossed • It is important to diagnose crossed fused renal
ectopia. ectopia prior to any surgical intervention.
• The upper pole of the crossed kidney usually • The blood supply to cross-fused kidney is usu-
fuses to the lower pole of the normally posi- ally anomalous and angiography is recom-
tioned kidney. mended before surgical intervention.
• The kidney usually remains incompletely • The diagnosis can be confirmed with CT-scan,
rotated with the pelvis anterior. However, if MRU and isotope scanning.
complete rotation occurs prior to fusion, an S- • There is an increased incidence of associated
or sigmoid kidney results and the pelvices malformations including cardiac, musculo-
face in opposite directions. skeletal, genital, gastrointestinal, anorectal,
• The lump or disk kidney results from exten- and renal systems, and occasionally as part of
sive fusion of the developing kidneys. the VACTERL association.
• In the ‘L’ shaped kidney, the crossed kidney • The most common associated urological
assumes a transverse position. abnormality is VUR.
• It has also been described with pelvic • The incidence of renal ectopia in postmor-
malignant lipomatosis and an entire chro- tem studies varies from 1 in 500 to 1 in
mosomal translocation involving chromo- 1,290.
somes 1 and 6. • It occurs slightly more frequently on the left
• Crossed renal ectopia are usually asymptom- side.
atic and require no treatment unless complica- • 10 % of cases are bilateral.
tions develops. • It affects males and females equally.
• There is a relatively high incidence of chronic • It is prone to obstruction and infection.
renal disease in crossed renal ectopia, and • Ectopic kidney is also more prone to trauma.
long term follow up is important. • Around 50 % remain unrecognized through-
out life.
• Ectopic kidneys lie outside the renal fossa and
1.3.10 Ectopic Kidney (Figs. 1.19 may be located in:
and 1.20) – The pelvis
– The iliac fossa
• An ectopic kidney results from either incom- – The chest
plete, excess or abnormal ascent of the embry- – Crossed
onic kidney. • Simple renal ectopia refers to a kidney in the
• Renal ectopia may arise as a result of abnor- ipsilateral retroperitoneal space and is most
malities of the ureteric bud or metanephros, an commonly located in the pelvis but may be
abnormal vascular supply or genetic opposite the sacrum or below the aortic
abnormalities. bifurcation.
Figs. 1.19 and 1.20 Intravenous urography showing a right hydronephrotic pelvic kidney. Note also the partial dupli-
cation of the left ureter
• The lumbar or iliac ectopic kidney is fixed

above the iliac crest but below the level of L2 – Autosomal dominant polycystic kid-
and L3. ney disease (ADPKD)
• A thoracic kidney is exceedingly rare and is – Autosomal recessive polycystic kid-
due to excessive cranial migration prior to dia- ney disease (ARPKD)
phragmatic closure or delayed closure with • Simple (solitary) renal cyst
continued ascent. • Renal fusion and renal ectopia
• Ectopic kidneys are rarely normal. They are – Horseshoe kidney
often small, lobulated kidneys with abnormal – Crossed fused renal ectopia
rotation with extrarenal calyces and an irregu- – Ectopic kidney
lar vascular supply. • Pre tumorous conditions
• Associated abnormalities: (Nephroblastomatosis)
– The most common problem associated • Tumors presenting in antenatal and
with an ectopic kidney is vesico-ureteric early childhood period
reflux (VUR) which occurs in up to 85 % of – Mesoblastic nephroma
children. – Nephroblastoma
– Pelvi-ureteric junction (PUJ) obstruction is – Multilocular cystic nephroma
present in 33–52 %. – Wilms tumor
– This is frequently due to a high insertion
of the ureter on the renal pelvis, malrota-
tion of the kidney or an anomalous blood
supply which obstructs the collecting 1.4 Abnormalities of the Ureter
system.
– Renal calculi • Ureteral atresia (Figs. 1.21, 1.22, and 1.23):
– The contralateral kidney is abnormal in as – The ureter may be absent or fail to extend
many as 50 % of patients. to the bladder and end blindly.
– Contralateral renal agenesis occurs in 10 %. – It is associated with ipsilateral absent or
– Additional malformations of the cardiovas- multicystic kidney.
cular, respiratory, genital or skeletal sys- – Bilateral atresia is incompatible with life.
tems are common. – Unilateral atresia is usually asymptomatic
– Associated skeletal anomalies are most but may cause hypertension.
commonly scoliosis and hemivertebrae. • Duplication of the ureter:
– Genital malformations in females include – This is one of the most common congenital
duplication of the vagina, bicornuate uterus malformations of the urinary tract.
and hypoplasia or agenesis of the uterus or – Duplicated ureter or Duplex Collecting
vagina. System is a congenital condition in which
– The most common genital anomalies in the ureteric bud, the embryological origin
males are hypospadias and cryptorchidism. of the ureter, splits (or arises twice), result-
ing in two ureters draining a single kidney.
– It is the most common renal abnormality,
Congenital Renal Anomalies occurring in approximately 1 % of the
• Renal agenesis population.
• Renal hypoplasia – The additional ureter may result in a ure-
• Oligomeganephronia terocele, or be an ectopic ureter.
• Supernumerary kidneys – It is estimated that duplication of the ureter
• Renal dysplasia and multicystic kidney is found in 0.9 % of a series of autopsies.
• Polycystic kidney disease – It is more common in females and is often
bilateral.
1.4 Abnormalities of the Ureter 19
Figs. 1.21, 1.22, and 1.23 Intraoperative photographs showing multicystic dysplastic kidney with ureteric atresia
– Ureteral duplication is divided into two types: – It is often asymptomatic but commonly
• Partial ureteral duplication (Figs. 1.24 presents with persistent or recurrent uri-
and 1.25): nary tract infections.
– The two ureters drain into the bladder via a – Urinary tract infection is most commonly
single common ureter. due to vesicoureteral reflux.
– Partial, or incomplete, ureteral duplication – Urinary incontinence in females occurs in
is rarely clinically significant. cases of ectopic ureter entering the vagina,
• Complete ureteral duplication (Figs. 1.26 urethra or vestibule.
and 1.27): • Ureterocele (Figs. 1.28 and 1.29):
– The two ureters drain separately. – This is a sacculation of the bladder end of
– Complete ureteral duplication may result in the ureter that can occur either in the blad-
one ureter opening normally into the bladder, der or ectopically.
and the other being ectopic, ending in the – It is much more common in girls than in boys.
vagina, the urethra or the vulval vestibule. – In 10 % of cases it is bilateral.
– These cases occur when the ureteric bud – It may be asymptomatic or cause obstruc-
arises twice rather than splitting. tion, incontinence or infection.
Figs. 1.24 and 1.25 Intravenous urography showing partial duplication of the right ureter
COMPLETE DUPLICATION
PARTIAL
DUPLICATION
Figs. 1.26 and 1.27 Intraoperative photographs showing partial and complete duplication of the ureters
• Ectopic ureteral orifice: • Obstruction of the ureteropelvic junction

– This usually occurs with ureterocele and (Figs. 1.30, 1.31, 1.32, 1.33, 1.34, 1.35, 1.36,
duplication of the ureter. 1.37, 1.38, and 1.39):
– Single ectopic ureters are also seen. – This is a common congenital abnormality
– Boys may present with recurrent epididy- of the ureter where there is a partial
mitis, as the ureter drains directly into the obstruction at the junction between the
vas deferens or seminal vesicle. renal pelvis and upper ureter.
– Girls normally present with incontinence – The cause of obstruction can be intrinsic or
with continual dribbling despite normal extrinsic.
voiding.
1.4 Abnormalities of the Ureter 21
Fig. 1.28 Pelvic

ultrasound showing right
ureterocele
Fig. 1.29 Intraoperative

photograph showing an DILATED URETEROCELE
obstructed ureterocele. URETER
Note the massively dilated
ureter and also the small
atrophic kidney
ATROPHIC
KIDNEY
– Intrinsic obstruction is the commonest and – Continued severe obstruction will compro-
results from localized narrowing at the UPJ mise renal function and these cases need to
junction. be diagnosed and treated early.
– A crossing aberrant lower polar vessel is one – The diagnosis can be confirmed with post-
of the extrinsic causes of UPJ obstruction. natal ultrasound and CT-urography or mag-
– It is seen more commonly in boys than in girls. netic resonance urography.
– Most cases are unilateral and usually on the – The function of the kidney can be assessed
left. with an isotope renogram.
– There are also bilateral cases of UPJ • Obstructed mega-ureter (Figs. 1.40, 1.41,
obstruction. 1.42, 1.43, and 1.44):
– The degree of obstruction will determine – This is caused by obstruction at the ure-
its effect on the kidneys. terovesical junction.
– With the widespread use of antenatal ultrasound, – It is four times more common in boys than
most of these cases are diagnosed in utero. in girls and is often bilateral.
– The presentation is variable depending on – Often, it is associated with absent or dys-
the degree of obstruction. plastic contralateral kidney.
Figs. 1.30 and 1.31 Intravenous urography showing bilateral hydronephrosis secondary to utero-pelvic junction
obstruction (UPJ) and a nephrostogram showing right hydronephrosis secondary to UPJ obstruction
– Most of these cases are diagnosed using 1.5 Abnormalities of the Bladder
ultrasound.
– It may be asymptomatic or present with • Bladder Exstrophy (Figs. 1.45, 1.46, and 1.47)
hematuria, recurrent urinary tract infection – This is one of the most severe urological
or abdominal pain. anomalies.
– Symptomatic patients are treated with ure- – It is characterized by absence of the ante-
teral reimplantation with tapering of the rior abdominal wall and the wall of the wall
dilated ureter. of the urinary bladder is open to the
outside.
– It is associated with other abnormalities,
Congenital Abnormalities of the Ureter especially epispadias.
• Ureteral atresia – The pubic bones are widely separated.
• Duplication of the ureter – It requires surgical reconstruction.
• Ureterocele • Cloacal exstrophy (Figs. 1.48, 1.49, 1.50, and
• Ectopic ureteral orifice 1.51):
• Obstruction of the ureteropelvic junction
• Obstructed mega-ureter
1.5 Abnormalities of the Bladder 23
Figs. 1.32, 1.33, 1.34, and 1.35 Intravenous urography with an isoptoe renogram. A split renal function less than
and CT-urography showing left and right hydronephrosis. 40 % indicate a severe degree of obstruction. This as well
Note the thickness of the renal parenchyma in the as the size of the renal pelvis will determine the urgency
CT-urography indicative of sever UPJ obstruction. The of surgical intervention
function of the kidney in these patients can be assessed
APPARENT VESSEL URETER
APPARENT VESSEL
Figs. 1.36, 1.37, 1.38, and 1.39 CT-urography showing hydronephrosis secondary to UPJ obstruction and intraop-
erative photographs showing apparent lower polar vessels causing pressure and obstruction of the ureter
Figs. 1.40 and 1.41 Intravenous urography showing caliber of the distal part of the ureter followed by proxi-
right megaureter and intraoperative photograph showing mal dilatation of the ureter
reimplantation of a primary megaureter. Note the small
– Cloacal exstrophy is a severe birth defect • It is thought that it results from an

where the urinary bladder and pat of the abnormality during early embryologic
intestines are exposed to the outside. development associated with rupture of
– Cloacal exstrophy is a major birth defect the cloacal membrane before fusion
representing the severe end of the spectrum with the urorectal septum.
of the exstrophy-epispadias complex. • Genetic and environmental factors may
– It is characterized by the followings: play a role in the etiology.
• Omphalocele – Prenatal diagnosis of cloacal exstrophy is
• Bladder extrophy (two exstrophied possible from ultrasound findings:
hemibladders separated by a foreshort- • Non-visualization of the bladder
ened hindgut or cecum, often blind-end- • Anterior abdominal wall defect
ing resulting in an imperforate anus). • Omphalocele
• Anterior lower abdominal wall defect • Myelomeningocele
• Widened and separated pubic bones – Omphalocele is found in 88–100 % of
• Splitting of both male (penis) and patients.
female (clitoris) external genitalia – Gastrointestinal malrotation/duplication and
• Anorectal agenesis or anteriorly placed short bowel syndrome are present in 46 %,
anus with absorptive dysfunction in some cases.
• Spinal defects – The symphysis pubis is widely separated
– Cloacal exstrophy is an extremely rare and the pelvis is often asymmetrically
birth defect, present in 1/200,000 and shaped.
1/400,000 live births. – Duplication of the vagina and uterus, as
– The exact pathogenesis of cloacal exstro- well as vaginal agenesis, has also been
phy is not known. reported.
Figs. 1.42, 1.43, and 1.44 Abdominal ultrasound show- showing reimplantation of the right megaureter. Note the
ing a right megaureter and a micturating cystourethro- narrow distal ureteric segment and a more dilated proxi-
gram showing no reflux. An intraoperative photograph mal ureter
– Various urological malformations may also • Persistent urachus (Figs. 1.52, 1.53 , 1.54 ,
be present including: 1.55 , 1.56, 1.57 , 1.58 , 1.59 , 1.60, and
• Ureteropelvic junction obstruction 1.61 ):
• Ectopic pelvic kidney – The lumen of the allantois, which connects
• Horseshoe kidney the bladder and the anterior abdominal wall
• Renal hypo- or agenesis closes normally.
• Megaureter – Persistent urachus results from failure of
• Ureteral ectopy this connection to become obliterated.
• Ureterocele – It may appear as a draining umbilical sinus
– Spinal abnormalities ranging from hemi- and can become infected.
vertebra to myelomeningocele occur in – It may appear as fistula connecting the uri-
most patients and may be accompanied by nary bladder to the umbilicus and the pres-
skeletal and limb anomalies (clubfoot ence of outflow obstruction, urine will be
deformities, absence of feet, tibial/fibular seen coming through the umbilicus.
deformities, and hip dislocation). • Contracture of the bladder neck:
– The diagnosis of cloacal exstrophy is clear – This is a common cause of reflux, bladder
clinically and the management of these diverticula and irritable bladder.
patients require multidisciplinary team • Bladder diverticulum (Figs. 1.62, 1.63, 1.64,
approach. 1.65, 1.66, and 1.67):
BLADDER
EXSTROPHY
PROLAPSED
VAGINA
Figs. 1.45, 1.46, and 1.47 Clinical photographs the granular appearance of the bladder mucosa in the
showing bladder exstrophy in a male and two females. second one and also the associated prolapsed ovary in
Note the associated epispadias in the first one. Note also the third one
– A bladder diverticulum is an outpouching – Anterior urethral valves

in the bladder wall. The bladder mucosa – Urethral strictures
herniates through the muscular wall of the – Neuropathic bladder
urinary bladder. – External sphincter dyssynergy
– It can be either congenital or acquired. – Herniation of the bladder mucosa
– Acquired bladder diverticula: through the ureteral hiatus after ure-
• These are often due to bladder outlet teral reimplantation is an iatrogenic
obstruction from an enlarged prostate, cause of bladder diverticulum.
urethral stricture or neurologic disease. • They tend to be multiple and occur in
• Acquired diverticula are most typically trabeculated bladders.
seen in elderly men and often associated • Many diverticula that are related to
with benign prostatic hyperplasia obstruction spontaneously resolve after
(BPH). relief or correction of the obstruction.
• Acquired diverticula are the result of • In some cases, the diverticula that occur
obstruction, infections, or iatrogenic in response to obstruction serve a bene-
causes. ficial function by acting as pressure
• The common causes include: pop-off mechanism, protecting the kid-
– Posterior urethral valves ney and ureters from high pressures.
Figs. 1.48, 1.49, 1.50, and 1.51 Clinical photographs cele in the second two pictures. Note also the associated
showing cloacal exstrophy. Note the associated omphalo- club feet in the fourth picture
cele in the first two and absence or very small omphalo-
Figs. 1.52 and 1.53 Abdominal ultrasound showing a cyst infront of the urinary bladder and a clinical photograph
showing urachal cyst
PATENT URACHUS
Figs. 1.54 and 1.55 Diagrammatic representation of site of the umbilicus. Note also the feeding tube which
patent urachus and a clinical photograph of a patient with was passed from the urethra and passed all the way to the
patent urachus. Note the patent channel connecting the umbilicus via a patent urachus
urinary bladder with the anterior abdominal wall at the
UMBILICAL BLADDER
SINUS DIVERTICULUM
Figs. 1.56 and 1.57 Diagrammatic representation of an gram represent an obliterated distal part of the urachus
umbilical sinus where the distal part of the urachus remain while the part attached to the bladder remain patent as a
patent and the rest becomes obliterated. The second dia- bladder diverticulum
– Congenital bladder diverticula: infection and urinary retention are the

• These are usually diagnosed in child- most frequent presentation forms.
hood or on prenatal ultrasound. • Some children with diverticula have
• Congenital bladder diverticula have a voiding dysfunction on urodynamic
wide clinical spectrum and could lead to testing. Whether the voiding dysfunc-
severe kidney damage. Urinary tract tion leads to the formation of diverticula
Figs. 1.58 and 1.59 Clinical photographs showing an sinus for a small distance. Intraoperatively, this was found
umbilical sinus. Note the opening in the umbilicus which to be a urachal sinus with the distal part obliterated and
is discharging. Note the probe which is passed into the connected to the bladder
– Diverticular size can vary greatly, with

URACHAL CYST some attaining a size equal to or greater
than the volume of the bladder.
– Diverticula can be wide- or
narrow-mouthed.
– Narrow-mouthed diverticula often empty
poorly leading to stasis of urine within
diverticula which can be complicated by
urinary tract infection, stone formation or
epithelial dysplasia.
– Depending on the size and location, blad-
der diverticula may cause ureteral obstruc-
Fig. 1.60 A diagrammatic representation of a urachal tion, bladder outlet obstruction, or VUR.
cyst • Ureteral obstruction is unusual, occur-
ring in approximately 5 % of children
or the presence of diverticula leads to with bladder diverticulum.
voiding dysfunction is unclear. • Bladder outlet obstruction is rare.
– Bladder diverticula most commonly occur • VUR is more common, affecting 8–13 %
lateral and superior to the ureteral of patients.
orifices. – Congenital or acquired diverticula do not
– They may also occur at the dome of the always require treatment, particularly if
bladder, particularly in such disorders as they are not associated with urinary infec-
bladder outlet obstruction (i.e., posterior tions, bladder stones, or urinary reflux.
urethral valves) or Eagle Barrett syndrome – Bladder diverticula associated with bladder
(prune belly syndrome). tumors, recurrent infection, or urinary
– Congenital deficiency or weakness in the retention do need treatment.
Waldeyer fascial sheath has been impli- – Excision of bladder diverticulum can be done
cated as a cause. through an open or laparoscopic approach.
– Congenital diverticula tend to be solitary – During surgical excision of these diverticula,
and are located at the junction of the blad- it is important to avoid ureteral injury due to
der trigone and detrusor. its close proximity to the diverticulum.
– This location, close to the insertion of the • Bladder ears:
ureter into the bladder, is important because – Normally, in infants, the bladder assumes a
large diverticula can impinge on or distort more abdominal position, which places it in
the ureteral orifices. close proximity to the internal inguinal ring.
VUR
BLADDER
DIVERTICULUM
POSTERIOR
URETHRAL VALVE
Fig. 1.62 A micturating cystourethrogram showing pos-

terior urethral valve. Note the associated VUR and blad-
Fig. 1.61 A diagrammatic representation of a patent ura- der diverticulum
chus with prolapse of the mucosa
Figs. 1.63, 1.64, 1.65, and 1.66 Pelvic ultrasound and micturating cystourethrogram showing congenital bladder
diverticulum. Note the narrow neck of the diverticulum
– With growth, the pelvis becomes more – Megacystis is associated with massive
developed, and the bladder assumes a more high-grade VUR.
pelvic position. – In the presence of massive reflux, a large
– Bladder ears are lateral protrusions of the percentage of the voiding bladder volume
bladder wall through the internal inguinal is refluxed into the upper tracts.
ring and into the inguinal canal. – This causes constant recycling of the urine
– Bladder ears are rarely seen in adults. between the bladder and ureters, resulting
– Bladder ears are diagnosed using: in progressive dilation of both.
• Voiding cystourethrography (VCUG) – Megacystis can be seen in other conditions,
• Intravenous pyelography (IVP) such as:
• CT-scan • Posterior urethral valves
– Bladder ears are best seen when the blad- • Ehlers-Danlos syndrome
der is filled and distended. • Urethral diverticulum
– It is important to recognize and diagnose • Microcolon hypoperistalsis syndrome
bladder ears. • Sacral meningomyelocele
– This is specially so during the repair of • Sacrococcygeal teratoma
inguinal hernia to avoid injury to the blad- • Pelvic neuroblastoma
der which can be mistaken as a large hernia • Bladder duplication:
sac. – Bladder duplication is a very rare
• Bladder agenesis: malformation.
– Bladder agenesis is a very rare congenital – It is divided into two types:
malformation. • Complete bladder duplication
– It is generally incompatible with life. • Partial bladder duplication
– All reported cases were seen in females – Complete bladder duplication is more com-
– This is because females have less outlet mon than incomplete duplication.
resistance than males and have preserva- – With complete bladder duplication, two
tion of renal function. urethras exist; with incomplete bladder
– In bladder agenesis, the ureters may enter duplication, the bladder joins distally into a
into the urethra, vagina, Gartner duct cyst single common urethra.
(female), prostatic urethra, rectum, or the – The two halves of the bladder are on either
patent urachus. side of the midline, with the corresponding
– Bladder agenesis are often associated with ipsilateral ureter draining each bladder half.
hydroureteronephrosis and renal dysplasia. – Associated anomalies occur more commonly
– Other associated anomalies include neuro- in those with complete bladder duplication.
logic, orthopedic, hindgut, and other uro- – These anomalies include:
genital anomalies, such as renal agenesis • Duplication of the penis, vagina, uterus,
and absence of the prostate, vagina, semi- lumbar vertebrae, and hindgut.
nal vesicles, epididymis, or penis. • In addition, fistulas may be present
• Megacystis (Figs. 1.67, 1.68, 1.69, 1.70, and between the rectum, vagina, and urethra.
1.71): • Bladder septation:
– Megacystis is an abnormally enlarged uri- – Bladder septation anomalies are rare.
nary bladder. – Fibromuscular or mucosa septations divide
– This may result secondary to overfilling of the bladder into equal or unequal portions.
the fetal bladder during development. – Septations may be complete or incomplete.
– This can be discovered antenatally on – The functioning of the associated renal
ultrasound or postnatally during evaluation units depends on the adequacy of upper
of febrile urinary tract infection. tract drainage.
1.6 Abnormalities of the Penis and Urethra in Males 33
Figs. 1.67, 1.68, and 1.69 Abdominal CT-scan, micturating cystourethrogram and a clinical intraoperative photo-
graph showing megacystis in a patient with microcolon hypoperistalisis syndrome
1.6 Abnormalities of the Penis

Congenital Abnormalities of the Bladder and Urethra in Males
• Bladder exstrophy
• Persistent urachus • Apenia:
• Contracture of the bladder neck – Apenia is a congenital absence of the penis
• Bladder diverticulum – It is extremely rare.
• Bladder ears – More than 50 % of patients have associated
• Bladder agenesis genitourinary anomalies such as
• Megacystis cryptorchidism, renal agenesis and dysplasia.
• Bladder duplication • Diphallia:
• Bladder septation – Diphallia, penile duplication (PD), diphal-
lic terata, or diphallaspartus is a rare devel-
opmental abnormality.
Figs. 1.70 and 1.71 Abdominal CT-scan showing megacystis in a patient with duplex system and
hydroureteronephrosis
– It is extremely rare with an estimated inci- – This is an extremely rare congenital

dence of 1 in 5.5 million boys, condition.
– The first reported case was by Johannes – There are several variations of this,
Jacob Wecker in 1609. ranging from duplication of the glans
– It is characterized by a male infant with alone to duplication of the entire
two penises. lower genitourinary tract.
– Infants born with penile diphallia usually are – The urethral opening can be in nor-
accompanied by renal, vertebral, hindgut, mal position or in a hypospadiac or
anorectal or other congenital anomalies. epispadiac position.
– There is also a higher risk of spina bifida. • Megalopenis (Figs. 1.72 and 1.73):
– Duplication of the penis, or diphallia, is a – Megalopenis is an abnormally enlarged
rare anomaly resulting from incomplete penis.
fusion of the genital tubercle. – It is seen in children with high level of tes-
– There are two distinct forms of penile tosterone production.
duplications: – It is seen also in patients with congenital
• The most common form is associated adrenal hyperplasia.
with bladder-exstrophy complex. • Micropenis:
– The patient exhibits a bifid penis, – Micopenis is defined as an abnormally
which consists of two separated cor- small but otherwise normally formed penis.
pora cavernosa that are associated – The stretched length of the penis is less
with two separate hemiglans. than 2.5 standard deviation below the
• The second form is a true diphallia mean.
1.6 Abnormalities of the Penis and Urethra in Males 35
Figs. 1.72 and 1.73 Clinical photographs showing megalopenis
– It is important to distinguish miscropenis – The effect depends on the severity of the

from buried and webbed penis, which is stricture.
usually of normal size. – Severe strictures can affect the bladder and
– The most common causes of micropenis also lead to hydroureter and hydronephro-
are: sis which can damage the kidney from back
• Hypogonadotropic hypogonadism pressure of urine.
– Impaired secretion of gonadotrophin- • Posterior urethral valves (Figs. 1.76 and 1.77):
releasing hormone (GnRH) by the – This is a relatively common congenital
hypothalamus occurs in some hypo- malformation,
thalamic dysfunctions such as – It is seen in male neonates and infants.
Kallmann’s syndrome and Prader- – Posterior urethral valves are found at the
Willi syndrome. distal prostatic urethra.
• Hypergonadotropic hypogonadism – They look like thin membranes and cause
– The testes are functionally impaired varying degrees of obstruction with back-
as in gonadal dysgenesis. pressure effect on the bladder, ureters and
• Idiopathic micropenis kidneys.
– There is normal hypothalamic- • Hypospadias (Figs. 1.78, 1.79, 1.80, 1.81, and
pituitary-testicular endocrine 1.82):
function. – This is one of the common urological mal-
• Congenital urethral stricture (Figs. 1.74 and formations in males.
1.75): – It occurs in around 1 in 250–300 male
– This is a rare congenital malformation. births.
– The two most common sites for congenital – The urethral meatus is found on the ventral
urethral stricture are: surface of the penis.
• The fossa navicularis – Around 7 % of patients have an additional
• The membranous urethra family member with hypospadias.
Figs. 1.74 and 1.75 Micturating cystourethrograms showing congenital urethral stricture
– Hypospadias is classified based on the site as those observed in bladder exstrophy

of the abnormal urethral meatus into: and/or diastasis of the pubic bones.
• Glanular • Females with epispadias have a bifid clito-
• Coronal ris and separation of the labia.
• Subcoronal • Incontinence is a common problem in
• Distal penile those with severe epispadias.
• Midpenile
• Proximal penile
• Penoscrotal
• Perineal Congenital Abnormalities of the Male
– The site of the abnormal urethral meatus is External Genitalia and Urethra
variable but most cases occur on the distal • Apenia
penis or corona. • Diphallia
– Around 10 % of children with hypospadias • Megalopenis
also have cryptorchidism. • Micropenis
– 9–15 % of cases also have an open proces- • Congenital urethral stricture
sus vaginalis or inguinal hernia. • Posterior urethral valves
• Epispadias (Figs. 1.83, 1.84, 1.85, 1.86, 1.87, • Hypospadias
and 1.88): • Epispadias
• Epispadias is a relatively rare congenital
malformation.
• It affects males more than females.
• Epispadias occurs in 1 in 120,000 males 1.7 Abnormalities of Female
and 1 in 450,000 females. External Genitalia
• In epispadias, the urethral opening is
abnormally located on the dorsal aspect of • Distal urethral stenosis:
the penis. – This occurs in young girls with enuresis
• The extent of the defect can vary from a with slow and interrupted stream and recur-
mild glandular defect to complete defects, rent infection.
1.7 Abnormalities of Female External Genitalia 37
Figs. 1.76 and 1.77 Micturating cystourethrogramms showing posterior urethral valve. Note the dilated posterior
urethra. Note also the associated unilateral VUR
– It is associated with secondary spasm of

the external sphincter.
• Labial fusion:
– Fused labia minora are relatively
common.
– The two labia minora are fused together.
– They can cause recurrent urinary infec-
tion as a result of obstruction to the urine
flow.
– Treatment is simple by separating the two
labia minor
– The use of estrogen cream can be prevent
recurrence which is common in these patients.
Fig. 1.78 A clinical photograph showing hypospadias. Note • Female epispadias:
the site of urethral opening which is located more proximally – Female epispadias is extremely rare.
Figs. 1.79 and 1.80 Clinical photographs showing distal and mid penile hypospadias
Figs. 1.81 and 1.82 Clinical photographs showing severe degrees of hypospadias (Penoscrotal and perineal
hypospadias)
1.7 Abnormalities of Female External Genitalia 39
Figs. 1.83 and 1.84 Clinical photographs showing spadias. This type has an excellent prognosis as the
glanular epispadias. Note the urethral opening on the dor- urethral sphincter is normal in these patients
sum of the glans. This is considered a rare variant of epi-
Figs. 1.85 and 1.86 Clinical photographs showing complete epispadias that is not associated with bladder exstrophy.
Note the extent of the epispadias opening and note also the associated dorsal curvature of the penis
– The reported incidence is approximately 1 – The two parts of the clitoris are sutured
of 500,000–600,000 live girls. together and the urethra is positioned in its
– Epispadias in females is commonly associ- normal place.
ated with separated pubic bones. – The prognosis of these patients is good and
– Female epispadias is characterized by: fertility is not affected.
• A bifid clitoris. • Clitoral hypertrophy (Figs. 1.89, 1.90, and 1.91):
• Diastases of the corpora cavernosa. – Clitoromegaly (or macroclitoris) is an
• Flattening of the mons. abnormal enlargement of the clitoris.
• Separation of the labia. – It is also called clitoromegaly.
– The diagnosis of epispadias in females is – It is commonly congenital but can be
always delayed as the defect may not be acquired following the use of anabolic ste-
obvious. roids, including testosterone.
– The bladder neck is almost always involved in – Clitoromegaly is commonly caused by
these patients leading to urinary incontinence. fetal exposure to androgens as seen in those
– Repair of female epispadias is much simpler. with congenital adrenal hyperplasia.
Figs. 1.87 and 1.88 Clinical photographs showing epi- repaired while in the second one bladder exstrophy clo-
spadias as part of the epispadias-exstrophy complex. In sure was already done. The size of the phallus was
the first photograph, the bladder exstrophy is still not increased by long acting testosterone
Figs. 1.89 and 1.90 Clinical photographs showing clitromegaly in a patient with congenital adrenal hyperplasia
– Rarely, it may also be due to in utero expo- – It is a rarely diagnosed in female children
sure to progestational agents or idiopathic and commonly occurs in prepubertal
virilisation. females and postmenopausal women.
– Clitoromegaly should not be confused with – Extremely rare, the urethral prolapse can
dermoid cyst of the clitoris. become strangulated.
• Urethral prolapse: – Vaginal bleeding is the most common
– Urethral prolapse is a circular protrusion of presenting symptom of urethral
the distal urethra through the external meatus. prolapse.
Further Reading 41
8. Gubler MC. Renal tubular dysgenesis. Pediatr

Nephrol. 2014;29:51.
9. Harris J, Robert E, Källén B. Epidemiologic charac-
teristics of kidney malformations. Eur J Epidemiol.
2000;16:985.
10. Kluth D, Fiegel HC, Geyer C, et al. Embryology of
the distal urethra and external genitals. Semin Pediatr
Surg. 2011;20:176–87.
11. Krishnan A, de Souza A, Konijeti R, et al. The anat-
omy and embryology of posterior urethral valves.
J Urol. 2006;175:1214–20.
12. Nakai H, Asanuma H, Shishido S, Kitahara S, Yasuda
Fig. 1.91 A clinical photogram showing dermoid cyst of K. Changing concepts in urological management of
the clitoris which can be confused with cliteromegaly the congenital anomalies of kidney and urinary tract,
CAKUT. Pediatr Int. 2003;45(5):634–41.
– Clinically, a round doughnut-shaped mucosa 13. Piscione TD, Rosenblum ND. The malformed kidney:
disruption of glomerular and tubular development.
is seen protruding from the urethral opening.
Clin Genet. 1999;56:341.
– Management of urethral prolapse ranges 14. Sanna-Cherchi S, Caridi G, Weng PL, et al. Genetic
from medical therapy that consists of approaches to human renal agenesis/hypoplasia and
topical estrogen use to conservative surgi- dysplasia. Pediatr Nephrol. 2007;22:1675.
15. Sanna-Cherchi S, Ravani P, Corbani V, et al. Renal
cal excision when medical therapies fail.
outcome in patients with congenital anomalies of the
kidney and urinary tract. Kidney Int. 2009;76:528.
16. Schedl A. Renal abnormalities and their developmen-
tal origin. Nat Rev Genet. 2007;8(10):791–802.
Congenital Abnormalities of the Female 17. Seikaly MG, Ho PL, Emmett L, et al. Chronic renal
External Genitalia and Urethra insufficiency in children: the 2001 annual report of
• Distal urethral stenosis the NAPRTCS. Pediatr Nephrol. 2003;18:796.
• Labial fusion 18. Shnorhavorian M, Bittner R, Wright JL, Schwartz
SM. Maternal risk factors for congenital urinary
• Clitoral hypertrophy anomalies: results of a population-based case-control
• Urethral prolapse study. Urology. 2011;78:1156.
19. Song R, Yosypiv IV. Genetics of congenital anomalies
of the kidney and urinary tract. Pediatr Nephrol.
2011;26(3):353–64.
20. Viana R, Batourina E, Huang H, et al. The develop-
Further Reading ment of the bladder trigone, the center of the anti-
reflux mechanism. Development. 2007;134:3763–9.
1. Bertram JF, Douglas-Denton RN, et al. Human neph- 21. Weizer AZ, Silverstein AD, Auge BK, et al.
ron number: implications for health and disease. Determining the incidence of horseshoe kidney from
Pediatr Nephrol. 2011;26:1529–33. radiographic data at a single institution. J Urol.
2. Caiulo VA, Caiulo S, Gargasole C, et al. Ultrasound 2003;170(5):1722–6.
mass screening for congenital anomalies of the kidney 22. Westland R, Schreuder MF, Ket JC, van Wijk
and urinary tract. Pediatr Nephrol. 2012;27:949. JA. Unilateral renal agenesis: a systematic review on
3. Chowdhary SK, Lander A, Parashar K, Corkery associated anomalies and renal injury. Nephrol Dial
JJ. Single-system ectopic ureter: a 15-year review. Transplant. 2013;28:1844.
Pediatr Surg Int. 2001;17(8):638–41. 23. Wiesel A, Queisser-Luft A, Clementi M, et al.
4. Daneman A, Alton DJ. Radiographic manifestations Prenatal detection of congenital renal malformations
of renal anomalies. Radiol Clin North Am. by fetal ultrasonographic examination: an analysis of
1991;29(2):351–63. 709,030 births in 12 European countries. Eur J Med
5. Decter RM. Renal duplication and fusion anomalies. Genet. 2005;48(2):131–44.
Pediatr Clin North Am. 1997;44:1323. 24. Yavuz S, Kıyak A, Sander S. Renal outcome of chil-
6. Glassberg KI. Normal and abnormal development of dren with horseshoe kidney: a single-center experi-
the kidney: a clinician’s interpretation of current ence. Urology. 2015;85:463.
knowledge. J Urol. 2002;167:2339. 25. Yiee JH, Baskin LS. Penile embryology and anatomy.
7. Gribouval O, Gonzales M, Neuhaus T, et al. Mutations Scientific World Journal. 2010;10:1174–9.
in genes in the renin-angiotensin system are associ- 26. Zalel Y, Pinhas-Hamiel O, Lipitz S, et al. The develop-
ated with autosomal recessive renal tubular dysgene- ment of the fetal penis – an in utero sonographic evalua-
sis. Nat Genet. 2005;37:964. tion. Ultrasound Obstet Gynecol. 2001;17:129–31.
Hydronephrosis in Infants
and Children 2
2.1 Introduction – Urinary incontinence

– Hematuria
• The word “hydro” represents “water” and – Febrile urinary tract infections
“nephro” represents “kidney”. • Hydronephrosis should be graded accurately
• Hydronephrosis means “water inside the in order to make good clinical decisions con-
kidney”. cerning the management and follow-up.
• Hydronephrosis is defined as distension and • There are currently two methods to grade the
dilation of the renal pelvis and calyces degree of hydronephrosis:
(Figs. 2.1 and 2.2). – The simple classification system of “mild,
• Hydroureteronephrosis refers to distention of moderate, and severe” is less accurate.
both the ureter and the renal pelvis and – The Society for Fetal Urology (SFU) has
calices. developed a more accurate numerical
• Hydronephrosis is usually caused by obstruc- grading system for hydronephrosis.
tion of the free flow of urine from the kidney. • The causes of hydronephrosis can be congeni-
• Hydroureteronephrosis is usually caused by tal or acquired.
obstruction at the uretrovesical junction or • It is important to understand that hydronephro-
below. sis does not always mean there is obstruction to
• The signs and symptoms of hydronephrosis the flow of urine from the kidney and hydrone-
depend upon: phrosis is a secondary effect of some other dis-
– Whether the obstruction is acute or chronic ease. Thus, the terms hydronephrosis and
– Whether the obstruction is partial or obstruction should not be used interchangeably.
complete • With the widespread use of prenatal ultrasounds,
– Whether the obstruction is unilateral or antenatal hydronephrosis is currently the most
bilateral common diagnosed prenatal condition.
– Hydronephrosis that occurs acutely with • Hydronephrosis can be caused by obstruction
sudden onset can cause intense pain in the anywhere along the upper or lower urinary tract.
flanks (Dietl’s crisis). – Obstruction that occurs anywhere along the
• If symptoms occur they can include: upper urinary tract will lead to increased
– Back, flank or lower abdominal pain pressure within the kidney.
– Nausea and vomiting – Obstruction occurring in the lower urinary
– Dysuria tract can also cause this increased pressure
– Burning during micturition through efflux of urine into the kidney.

44 2 Hydronephrosis in Infants and Children
Figs. 2.1 and 2.2 Intravenous urogram and a micturating cystourethrogram showing bilateral hydronephrosis and
unilateral hydroureteronephrosis
– This would eventually lead to: – In 15 %, the hydronephrosis persists (non-

• Urinary tract infection refluxing, non-obstructing hydronephrosis)
• Stone formation but spontaneously regress by age 3 years.
• Loss of renal function – In the remaining 35 %, a pathological cause
• Neonatal hydronephrosis can be caused by can be identified.
several abnormalities. These commonly • Extensive use of prenatal ultrasound has led to
include (Figs. 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, an increased rate of diagnosis of neonatal
and 2.9): hydronephrosis, of which ureteropelvic junc-
– Ureteropelvic junction obstruction tion obstruction is the most frequent cause.
– Vesicoureteral reflux • Ureteropelvic junction obstruction occurs in
– Ureterovesical junction obstruction approximately 1 in every 2,000 live births and
– Megaureter accounts for approximately half of the cases
– Ureterovesical junction obstruction and of prenatal hydronephrosis.
megaureter are fairly uncommon and, • In most cases, neonatal hydronephrosis second-
therefore, pediatric patients who have ary to ureteropelvic junction obstruction gradu-
hydronephrosis and a normal voiding cys- ally resolves without surgical intervention.
tourethrogram are presumed to have ure- • There is a strong correlation between the Society
teropelvic junction obstruction. for Fetal Urology (SFU) grade of hydronephrosis
• Prenatally diagnosed hydronephrosis: and the likelihood of spontaneous resolution:
– Approximately 50 % are transient and – Grade I resolves in approximately 50 % of
resolve by the time the infant is born. patients
2.2 Pathophysiology 45
Figs. 2.3 and 2.4 Intravenous urography and micturating cystourethrogram showing pelviureteric junction obstruction
and bilateral vesicoureteric reflux
– Grades II resolves in approximately 36 % • This interruption can occur anywhere along

of patients the urinary tract from the kidneys to the ure-
– Grade III resolves in approximately 16 % thral meatus.
of patients • Gross changes within the urinary tract
– Grade IV resolves in approximately 3 % of depend on:
patients – The duration of obstruction
• The initial severity of the hydronephrosis at – The degree of obstruction
the time of antenatal diagnosis and the pres- – The level of obstruction
ence of the hydronephrosis at birth were the • Within the intrarenal collecting system, the
only two factors that predicted hydronephro- degree of dilation is limited by surrounding
sis failure to resolve. renal parenchyma.
• Hydronephrosis that was mild to mild-to- • This is in contrast to the extrarenal compo-
moderate in severity resolved in 71 % of nents which can dilate to the point of
patients, compared to 28 % of children with tortuosity.
moderate to severe hydronephrosis. This sup- • Hydronephrosis can reasonably be viewed as
ports the claim that the severity of hydrone- a beneficial compensatory mechanism that
phrosis predicts failure of the lesion to resolve. actually protects the kidney against high intra-
pelvic pressures and further renal damage.
• The extent and persistence of these functional
2.2 Pathophysiology insults are directly related to the duration and
severity of the obstruction.
• Hydronephrosis can result from anatomic or – Brief disruptions lead to reversible func-
functional causes that interrupt the flow of tional disturbances with little associated
urine (Figs. 2.10 and 2.11). anatomic changes.
Figs. 2.5 and 2.6 A micturating cystourethrogrma show- In patients with megaureter, there is no anatomical
ing severe vesicoureteric reflux in a patient with a duplex obstruction at the uretrovesical junction and micturating
system. An intravenous urogram showing a negaureter cystourethrogram doe not show vesico ureteric reflux
with hydroureteronephrosis is seen in the second picture.
– More chronic disruptions lead to profound – It can be associated with little anatomic
tubular atrophy and permanent nephron disturbance to renal parenchyma.
loss. • Chronic hydronephrosis:
• The rise in ureteral or renal pelvic pressure – In chronic hydronephrosis, the loss of func-
leads to marked changes in glomerular filtration is usually irreversible even with cor-
tion, tubular function, and renal blood flow. rection of the obstruction.
• The glomerular filtration rate (GFR) declines – It may be associated with compression of
significantly within hours following acute the papillae, thinning of the renal
obstruction. This significant decline of GFR parenchyma around the calyces, and
can persist for weeks after relief of coalescence of the septa between calyces.
obstruction. – Eventually, cortical atrophy progresses to
• In addition, renal tubular ability to transport the point at which only a thin rim of
sodium, potassium, to concentrate and to parenchyma is present (Figs. 2.12, 2.13,
dilute the urine is severely impaired. and 2.14).
• Increased ureteral pressure also results in – Microscopic changes consist of dilation of
pyelovenous and pyelolymphatic backflow. the tubular lumen and flattening of the
• Acute hydronephrosis: tubular epithelium. Fibrotic changes and
– Acute hydronephrosis when corrected, usu- increased collagen deposition are observed
ally allows full recovery of renal function. in the peritubular interstitial tissue.
STENOSED
URETER
SEGMENT DILATED
URETER
DILATED
URETER
STENOSED
URETER
SEGMENT
Figs. 2.7, 2.8, and 2.9 An intravenous urogram showing two intraoperative picrures. Note the dilated ureter above
hydrouretronephrosis secondary to obstruction at the uret- the site of obstruction. This was treated by resection of the
rovesical junction. Note the ureter tappering at the lower stenotic part and reimplantation of the ureter
part. This was confirmed intraoperatively in the second
– Long-standing hydronephrosis may be – Infection

associated with obstructive nephropathy – Renal scarring
and renal failure. – Calculus formation
– Patients with complete or severe partial – Sepsis
bilateral obstruction also may develop • Hypertension is occasionally induced by renal
acute or chronic renal failure. obstruction.
• Urinary stasis as a result of obstruction may • The mechanism responsible for the elevation
be complicated by: in blood pressure varies with the duration and
type of obstruction.
Figs. 2.10 and 2.11 Two micturating cystourethrograms showing hydrouretronephrosis with dilated urinary bladder
secondary to posterior urethral valve. Note the tortuous dilated ureter
urinary tract obstruction or obstruction of

a solitary functioning kidney. The eleva-
tion in blood pressure resolves with the
diuresis following correction of the
obstruction.
– The plasma renin activity is also typically
DUPLEX URETER
normal in chronic unilateral obstruction,
and the elevation in blood pressure is unre-
lated to the renal disease.
Fig. 2.12 Intraoperative photograph showing an atrophic
kidney with dilated refluxing duplex system. Note the • The pathophysiological changes of hydrone-
markedly dilated duplex ureter phrosis depends on several factors which can
be summarized as follows:
– Acute, unilateral obstruction can cause – Persistent hydronephrosis will lead to the
hypertension via activation of the renin- following changes:
angiotensin system. • Dilatation of the renal pelvis and the
– The elevation in blood pressure is proba- intrarenal collecting system.
bly volume mediated as renin secretion is • The degree of dilatation is limited by
usually normal in patients with bilateral surrounding renal parenchyma.
2.3 Etiology of Hydronephrosis 49
• This will lead to compression of the • Renal scarring

papillae, thinning of the parenchyma • Calculus formation
around the calyces, and coalescence of • Sepsis
the septa between calyces. • Loss of renal function
• Eventually, cortical atrophy progresses – Longstanding hydronephrosis may be
to the point at which only a thin rim of associated with obstructive nephropathy,
parenchyma is present. hypertension and renal failure.
• Fibrotic changes and increased collagen
deposition are also observed in the peri-
tubular interstitium. 2.3 Etiology of Hydronephrosis
• The extrarenal dilatation can progress
leading to ureteral dilatation to the point • The etiology and presentation of hydronephrosis
of tortuosity. and/or hydroureter in adults differ from that in
– Urinary stasis in these patients may result neonates and children (Figs. 2.15, 2.16, 2.17,
in complications including: 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, 2.25, 2.26,
• Infection 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, and 2.34).
Figs. 2.13 and 2.14 Intraoperative photographs showing atrophic kidneys secondary to severe reflux and
hydroureters
Figs. 2.15 and 2.16 Intravenous urography showing (hydrometrocolpos) secondary to vaginal atresia. This
bilateral hydroureters and hydronehrosis secondary to will resolve once the vaginal atresia is treated
exteral compression by a distended vagina and uterus
Figs. 2.17, 2.18, and 2.19 MRI showing bilateral hydronephrosis and distended vagina secondary to vaginal atresia
DISTENDED UTERUS
Figs. 2.20 and 2.21 Inra-operative photographs show- the ureters leading to hydroureteronephrosis. Drainage of
ing hydrometrocolpos secondary to vaginal atresia. The the hydrometrocolpos will lead to relief of the obstruction
distended vagina and uterus will lead to compression on and resolution of the hydroureteronephrosis
Figs. 2.22 and 2.23 Plain abdominal x-ray and IVU showing a staghorn stone in a child causing hydronephrosis. The
stone took the shape of the renal pelvis and cayces. Note the stone is causing obstruction and hydronephrosis on the IVU
Figs. 2.24, 2.25, and 2.26 Intravenous urogram and voiding cystourethrogrms showing unilateral hydroureterone-
phrosis secondary to uretrovesical obstruction and posterior urethral valve
Figs. 2.27 and 2.28 A voiding cystourethrogram showing urethral stricture causing vesicoureteral reflux with hydro-
ureter and hydronephrosis
DILATED
URETEROCELEE URETER
Figs. 2.29, 2.30, 2.31, and 2.32 Abdominal and pelvic ultrasound and CT-scan showing right and left uretrocele with
hydroureter and hydronephrosis
• The causes of hydronephrosis with or without – Retroperitoneal fibrosis

hydroureter depends on: – Renal, bladder and ureteric calculi
– The site of obstruction – Vesicoureteric reflux
– Whether it is unilateral or bilateral – Posterior urethral valve
– Whether it is intrinsic, extrinsic or – Urethral stricture
functional. – Uretrocele
• The following are the main causes of hydrone- – Posterior urethral valves
phrosis in infants and children: – Urethral atresia
– Pelvi-ureteric junction obstruction – Phimosis and meatal stenosis
– Ureterovesical junction obstruction • Multi cystic dysplastic kidney (MCDK)
– Ureteral folds and valves (Figs. 2.35, 2.36, and 2.37):
– Benign fibroepithelial polyps – This will show several round, well defined,
– Retrocaval ureter cystic structures within the kidney that
– Neurogenic bladder often look just like severe hydronephrosis.
– Hydrocolpos and hydrometrocolpos – These abnormally developed kidneys are
– Bladder exstrophy generally found early in pregnancy through
– Duplicated renal collecting systems antenatal ultrasounds.
– Multi cystic dysplastic kidney – The true diagnosis can be confirmed post-
– Retroperitoneal lymphoma and sarcoma natally by the following tests:
URETROCELE
ATROPHIC
KIDNEY
URETROCELE
DILATED URETER
Figs. 2.33 and 2.34 A cystogram showing an uretrocele and intraoperative photograph showing a large ureterocel
causing obstruction and marked hydroureter and atrophic dysplastic kidney
• A post-natal ultrasound
• A voiding cystourethrogram
• A nuclear renal scan
– The renal scan confirms that the kidney has
no function.
– MCDKs have no function and will involute
(shrink up) over time.
– Rarely, these multi cystic dysplastic kid-
neys needs to be removed for the following
reasons:
• Very large multi cystic dysplastic
Fig. 2.35 CT-scan showing multicystic dysplastic kidney
kidney • If they fail to involute
• If they rupture
Figs. 2.36 and 2.37 Clinical photographs showing resected multicystic dysplastic kidneys
Figs. 2.38 and 2.39 Bilateral nephrostograms and CT-scan showing bilateral PUJ obstruction
• If they develop unmanageable high – Primary megaureter

blood pressure – Neurogenic bladder
• If they are complicated by severe – Severe meatal stenosis
infection • Acquired causes:
• There are several congenital and acquired – Kidney and ureteric stones
conditions that can lead to hydronephrosis in – Blood clots
infants and children. – Retroperitoneal fibrosis
• Congenital causes: – Urethral stricture
– PUJ (Pelvi-Ureteric Junction) obstruction – Tumors
– Posterior urethral valve • In children and in neonates, the relative fre-
– Uretro-vesical junction (UVJ) obstruction quency of the causes of antenatal hydrone-
– Vesicoureteric reflux phrosis has been determined to be as
– Abnormal polar vessels follows:
– Uretrocele – Transient (48 %)
2.4 Classification of Hydronephrosis 55
Figs. 2.40, 2.41, and 2.42 Abdominal CT-scan and nephrostograms showing unilateral hydronephrosis
– Physiologic (15 %) 2.4 Classification

– Ureteropelvic junction obstruction (11 %) of Hydronephrosis (Figs. 2.38,
– Vesicoureteral reflux (9 %) 2.39, 2.40, 2.41, and 2.42)
– Megaureter (4 %)
– Multicystic dysplastic kidney (2 %) • The widespread use of antenatal ultrasound
– Ureterocele (2 %) revealed a significant structural fetal anomaly
– Posterior urethral valves (1 %) in 1 % of pregnancies.
• The probability of detecting these abnormali- • Grading of antenatal hydronephrosis based on

ties depends on the experience and skills of renal pelvis antero-posterior diameter:
the sonographer. – Mild
• The distribution of these anomalies is as • Second trimester (4–6 mm)
follows: • Third trimester (7–9 mm)
– 50 % involve the central nervous system – Moderate
– 20 % are genitourinary • Second trimester (7–10 mm)
– 15 % are gastrointestinal • Third trimester (10–15 mm)
– 8 % are cardiopulmonary – Severe
• An abnormality involving the genitourinary – Second trimester (>10 mm)
tract may be expected in as many as 1 in 100 – Third trimester (>15 mm)
pregnancies.
• The prevalence of antenatally detected hydro- Renal pelvis antero-posterior diameter
nephrosis (ANH) is variable depending on the Classification Second trimester Third trimester
gestational age, diagnostic criteria and skills of Mild 4–6 mm 7–9 mm
the radiographer and ranges from 0.6 % to Moderate 7–10 mm 10–15 mm
5.4 %. Severe >10 mm >15 mm
• Among the genitourinary anomalies, hydrone-
phrosis is the commonest anomaly detected
antenatally. • The most common system used (Society of
• The causes and distribution of antenatally Fetal Ultrasound, SFU) was originally
diagnosed hydronephrosis are as follows: designed for grading neonatal and infant
– Transient hydronephrosis (40–80 %) hydronephrosis:
– Pelviureteric junction obstruction – Grade 0:
(10–30 %) • No dilatation, calyceal walls are
– Vesicoureteric reflux (10–20 %) opposed to each other
– Vesicoureteric junction obstruction – Grade 1 (mild):
(5–10 %) • Dilatation of the renal pelvis without
– Multicystic dysplastic kidney (5 %) dilatation of the calyces
– Duplex system (4–6 %) • No parenchymal atrophy
– Posterior urethral valve (1–2 %) – Grade 2 (mild):
– Others (Urethral atresia, Prune belly syn- • Dilatation of the renal pelvis (mild) and
drome, etc.) calyces (pelvicalyceal pattern is
• There are several systems to grade and clas- retained)
sify hydronephrosis. • No parenchymal atrophy
• Hydronephrosis can be classified depending – Grade 3 (moderate):
on the onset into: • Moderate dilatation of the renal pelvis
– Acute and calyces
– Chronic • Blunting of fornicies and flattening of
• Hydronephrosis is also classified depending papillae
on the degree of obstruction into: • Mild cortical thinning may be seen
– Complete – Grade 4 (severe):
– Partial • Gross dilatation of the renal pelvis and
• Hydronephrosis is also classified depending calyces, which appear ballooned
on the side into: • Loss of borders between the renal pelvis
– Unilateral and calyces
– Bilateral • Renal atrophy seen as cortical thinning
2.5 Clinical Features 57
The Society of Fetal Ultrasound (SFU) grading of spread and routine use of antenatal
hydronephrosis ultrasound.
Grade Description • Most cases of hydronephrosis in infants are
Grade 0 (mild) No dilatation, calyceal walls are incidentally detected by routine screening
opposed to each other ultrasounds.
Grade 1 (mild) Dilatation of the renal pelvis • Hydronephrosis diagnosed prenatally:
without dilatation of the calyces
– 50 % are transient and resolve spontaneously.
No parenchymal atrophy
– 15 % have hydronephrosis that persists but
Grade 2 (mild) Mild dilatation of the renal pelvis
and calyces is not associated with urinary tract obstruc-
(Pelvicalyceal pattern is retained) tion (non-refluxing, non-obstructive hydro-
No parenchymal atrophy nephrosis). For these children, regression
Grade 3 Moderate dilatation of the renal of the hydronephrosis occurs spontane-
(moderate) pelvis and calyces ously, usually by age 3.
Blunting of fornicies and flattening – 35 % have a definite pathological cause for
of papillae hydronephrosis. These include:
Mild cortical thinning may be seen • Pelvi-ureteric junction obstruction
Grade 4 (severe) Gross dilatation of the renal pelvis (11 %)
and calyces which appear
ballooned • Vesicoureteral reflux (9 %)
Loss of borders between the renal • Megaureter (4 %)
pelvis and calyces • Multicystic dysplastic kidney (2 %)
Renal atrophy seen as cortical • Ureterocele (2 %)
thinning • Posterior urethral valves (1 %)
• Hydronephrosis may be asymptomatic dis-
• The old system classify hydronephrosis in covered on ultrasound ordered for some other
infants and children into three grades: reason.
– Mild • Another presentation of hydronephrosis is uri-
– Moderate nary tract infection.
– Severe • Acute hydronephrosis secondary to a stone
• Obstructed hydronephrosis is also classified will cause severe flak pain.
according to the level of obstruction: • Chronic hydronephrosis is usually asymptom-
– Infravesical obstruction: atic or cause dull aching pain.
• Posterior urethral valves • Other clinical presentations of hydronephrosis
• Severe meatal stenosis and phimosis include:
• Severe urethral stricture – Nausea and vomiting
– Supravesical obstruction: – Urinary tract infection with abdominal
• Ureteropelvic junction obstruction pain, fever, dysuria, nausea and
• Primary megaureter vomiting.
• Uretrovesical obstruction – Hydronephrosis secondary to obstruction
at the bladder neck or urethra will lead to
distension of the urinary bladder. This can
2.5 Clinical Features cause lower abdominal pain and a palpable
mass.
• The majority of hydronephrosis cases are now – The enlarged kidney may be palpable.
diagnosed antenattaly as a result of the wide-
obstructive uropathy distal to the uretero-

Hydronephrosis Diagnosed Prenatally pelvic junction.
• Fifty percent are transient and resolve – An isolated hydronephrosis without dilata-
spontaneously. tion of the ureter is suggestive of pelvi-
• Fifteen percent have hydronephrosis ureteric junction obstruction.
that persists but is not associated with – The ultrasound is also valuable in evaluat-
urinary tract obstruction (non-refluxing, ing the renal parenchymal thickness. Sever
non-obstructive hydronephrosis). hydronephrosis will lead thinning of the
• Thirty five percent have a definite path- renal cortex thickness.
ological cause for hydronephrosis. – Ultrasonographic findings of posterior ure-
These include: thral valves are:
– Pelvi-ureteric junction obstruction • Bilateral hydrouretero-nephrosis
(11 %) • Dilated, thick walled bladder that fails
– Vesicoureteral reflux (9 %) to empty
– Megaureter (4 %) • Dilated posterior urethra
– Multicystic dysplastic kidney (2 %) • Intravenous urogram (IVU) (Figs. 2.48 and
– Ureterocele (2 %) 2.49):
– Posterior urethral valves (1 %) – Intravenous urography is a useful investi-
gation to outline the anatomy of the renal
system and locate the site of obstruction.
– This is rarely used nowadays as there are
2.6 Investigations and Diagnosis other more valuable and less invasive
investigations.
• Complete blood count and differential – Add to this, the radiation exposure in
• Serum electrolytes children.
• Blood urea and creatinine • A micturating cystourethrogram (MCU)
• Urine analysis and culture (Figs. 2.50, 2.51, and 2.52):
• Abdominal x-ray (Figs. 2.43 and 2.44): – This is performed in patients with unilat-
– This may show a soft tissue density on the eral or bilateral hydronephrosis to exclude
left or right lumbar regions representing the possibility of vesicoureteral reflux or
the enlarged kidney. anatomical abnormalities such as posterior
– Urolithiasis may cause hydronephrosis and urethral valves.
radiopaque stones may be seen on plain – Vesicoureteral reflux is present in 8–38 %
abdominal x-rays. of patients with unilateral or bilateral ante-
• Abdominal and pelvic ultrasound (Figs. 2.45, natal hydronephrosis, as compared to <1 %
2.46, and 2.47): in the general population.
– This is important in the detection of hydro- – MCU is indicated in the following
nephrosis and whether it is unilateral or conditions:
bilateral. • Infants with moderate to severe hydro-
– Ultrasound is also valuable in defining the nephrosis (SFU grade 3–4, or renal
degree of hydronephrosis. APD >10 mm)
– The size of the renal pelvis as measured by • Dilated ureter(s)
ultrasound is an estimate of the degree of • Bladder or urethral abnormalities
hydronephrosis in those with obstructive • Patients with history of milder grades of
hydronephrosis. antenatal hydronephrosis who show
– It is also important to evaluate the ureter worsening hydronephrosis, progressive
as dilatation of the ureter is seen in those parenchymal thinning or occurrence of
with vesicoureteral reflux (VUR) or UTI.
2.6 Investigations and Diagnosis 59
Figs. 2.43 and 2.44 Plain abdominal x-rays showing a soft tissue density in the left lumbar region representing
enlarged hydronephrotic left kidney on the left and a large staghorn calculus on the right side
Fig. 2.45 Abdominal and pelvic ultrasound showing a

right uretrocele
Fig. 2.47 Abdominal ultrasound showing an enlarged

left multicystic kidney
• Diuretic renography (Fig. 2.53):

– Pelviureteric junction obstruction should
be considered in infants with hydronephro-
sis, where dilating VUR is excluded.
– The likelihood of detecting obstruction is
considerably higher in patients with SFU
grade 4 or renal APD exceeding 20–30 mm.
– The possibility of vesicoureteric junction
obstruction or megaureter is considered in
patients with hydronephrosis and dilated
ureter where MCU is normal.
Fig. 2.46 Abdominal ultrasound showing a right hydro-
– Patients with VUR and worsening hydro-
nephrotic kidney nephrosis also require evaluation for pelvi-
Figs. 2.48 and 2.49 Intravenous urograms showing hydronephrotic left kidney
Figs. 2.50 and 2.51 Micturating cystourethrograms showing severe unilateral and bilateral vesicoureteral reflux. Note
the dilated tortous ureters
Fig. 2.52 A micturating

cystourethrogram showing
right vesicoureteral reflux.
Note also the dilated posterior
urethra diagnostic of posterior VESICOURETERA
urethral valve. Note also the L REFLUX
small bladder diverticulae
URINARY
BLDDER
POSTERIOR BLDDER
URETHRA DIVERTICULUM
ANTERIOR URETHRA
Fig. 2.53 A diuretic renogram of a child with left PUJ obstruction
ureteric junction obstruction, since the two since they show greater renal extraction
may coexist in 7–18 % of patients. and higher kidney to background ratio
– Diuretic renography allows differentiation compared to diethylenetriaminepentaacetic
between obstructive and non-obstructive acid (DTPA).
hydronephrosis and estimating relative • Renal urography includes the following two
renal function. phases:
– Radiopharmaceuticals such as 99mtechne- – First, radioisotope is injected intravenously
tium mercaptoacetyltriglycine (MAG3) or and renal parenchymal (cortical) uptake is
ethylenedicysteine (EC) are preferred, measured during the first 2–3 min. The rela-
tive contribution of each kidney to overall frusemide and micturition excludes sig-
renal function (called the split renal func- nificant obstruction.
tion) is assessed quantitatively and is useful • An obstructive pattern is defined by an
as a baseline study. ascending or plateau phase over 20 min
– Second, at peak renal uptake, intravenous that fails to empty following diuretic
furosemide is administered and the excre- administration and on post-micturition
tion of isotope from the kidney is mea- views.
sured, referred to as the washout curve. • Estimated differential renal function
This phase indicates the extent of obstruc- values between 45 % and 55 % are con-
tion, if present. sidered normal.
– The washout curve: • An initial differential function below
• In a healthy kidney, furosemide admin- 35–40 % in the kidney with obstructed
istration results in a prompt washout. drainage signifies impaired renal
• In a dilated system, if washout occurs function.
rapidly after diuretic administration • Other features that suggest obstruction
(<15 min), the system is not obstructed. include ipsilateral supranormal differ-
• If washout is delayed beyond 20 min, ential renal function (55 %) and pro-
the pattern is consistent with obstructive longed time to clear 50 % of the
uropathy. radionuclide (t1/2 >20 min).
• However, a delayed washout must be • Abdominal CT-scan (Figs. 2.54 and 2.55)
interpreted with caution. If washout is – Abdominal CT-scan is valuable in outlin-
from 15 to 20 min, the study is ing the extent of hydronephrosis and site of
indeterminate. obstruction.
– The split renal function: – It is also useful in measuring the renal
• Split renal function results are the most parenchyma thickness.
useful criteria to evaluate a decrease in • Magnetic resonance urography (MRU)
renal function. (Figs. 2.56, 2.57, 2.58, and 2.59):
• In patients with unilateral hydronephro- – MRU in children is becoming more com-
sis, if the normal nonhydronephrotic monly used in the diagnosis and manage-
kidney and hydronephrotic kidney both ment of congenital uropathies such as PUJ
have equal function, conservative man- obstruction.
agement without surgery is a safe option. – MRU is especially useful in the manage-
• A significant decrease in renal function ment of obstructed kidneys that have rota-
of one kidney is defined as 35 % or less tion or ascent anomalies, or are solitary.
differential renal function. – MRU can more clearly define the anatomy
• A decrease in differential renal function and delineate the proper surgical approach.
was associated with severe antenatal – The disadvantage of MRU is that the study
hydronephrosis (i.e., renal pelvic diameter often requires general anesthesia or heavy
>10 mm at 20–24 week gestation and conscious sedation in children.
>16 mm at 33 week gestation). – Furthermore, the contrast agent can only be
– A normal renogram curve is characterized by: used if renal function is normal because of
• An early peak (2–5 min), rapidly reports of irreversible renal fibrosis in
descending phase and almost complete patients with renal insufficiency.
renal emptying by 20 min. • Antegrade or retrograde pyelography is usu-
• Drainage is influenced by state of hydra- ally used to relieve, rather than diagnose, uri-
tion, and composite and differential kid- nary tract obstruction. These tests, however,
ney function. can also be performed for diagnosis when the
• The presence of satisfactory drainage history is highly suggestive (Figs. 2.60, 2.61,
spontaneously, or following IV 2.62, and 2.63).
2.7 Treatment 63
Figs. 2.54 and 2.55 Abdominal CT-scan showing two patients. I the second picture, there is hardly any renal
hydronephrosis secondary to PUJ obstruction. Note the tissue remaining
difference in the renal parenchyma thickness between the
Figs. 2.56 and 2.57 MRU showing bilateral severe hydroureteronephrosis. Note the marked dilated ureters
2.7 Treatment • The presence of infection should be treated

aggressively as infection with hydronephro-
• The aim of treatment is to remove the obstruc- sis may progress rapidly to sepsis.
tive cause and allow free drainage of the urine. • The presence of bilateral hydronephrosis or
• The specific treatment of patients with hydro- hydronephrosis in a solitary kidney calls for
nephrosis depends on the etiology and site of urgent evaluation and management.
obstruction.
Figs. 2.58 and 2.59 MRU showing severe right hydronephrosis secondary to pelvi-ureteric junction obstruction. Note
the compressed renal tissue
Figs. 2.60, 2.61, 2.62, and 2.63 Percutaneous nephrostograms showing unilateral and bilateral hydronephrosis sec-
ondary to PUJ obstruction
2.8 Antenatal Hydronephrosis 65
• A nephrostomy tube is a very valuable proce- in patients with mild VUR confers clinical
dure to relieve acute hydronephrosis benefit.
(Figs. 2.60, 2.61, 2.62, and 2.63). – Multiple studies and a systematic review
• The use of ureteral stent can bypass an suggest that the severity of antenatal hydro-
obstruction and temporarily relieve the pres- nephrosis does not correlate with the grade
sure on the affected kidney. of reflux, and that patients with VUR may
• Lower urinary tract obstruction can be relieved have normal postnatal ultrasound.
by insertion of a urinary catheter or a suprapu- – Infants with postnatally confirmed moder-
bic catheter. ate or severe hydronephrosis (SFU 3–4;
• Fetal surgery: renal APD >10 mm) or dilated ureter
– Fetal surgery is indicated in those with receive antibiotic prophylaxis while await-
antenatal severe hydronephrosis in an ing evaluation.
attempt to preserve renal function and • There are those who recommend that all
improve the clinical outcome. patients detected to have VUR receive antibi-
– It is however not readily available and otic prophylaxis through the first year of life.
require expertise. • Antibiotics that are preferred include cepha-
• Indication of surgical interventions in those lexin (10 mg/kg/day) during the first 3 months
with PUJ obstruction: of life, and cotrimoxazole (1–2 mg/kg/day) or
– Conservative management is appropriate nitrofurantoin (1 mg/kg/day) later.
for infants with an obstructive pattern on • Patients with moderate or severe hydronephro-
diuretic renography and differential func- sis and/or dilated ureter should receive antibi-
tion exceeding 40 %. otic prophylaxis while awaiting investigations.
– While most experts suggest that pyeloplasty • Since the risk of UTI is low with mild hydro-
be considered in patients showing nephrosis, antibiotic prophylaxis is not neces-
obstructed drainage and differential func- sary in these infants.
tion below 40 %, others propose surgery at
differential function below 35 %, or an
obstructed renogram with prolonged t1/2 2.8 Antenatal Hydronephrosis
>20 min.
– In those with PUJ, a reduction of differen- • The widespread use of antenatal ultrasound
tial renal function by more than 5–10 % has resulted in an increase in the early detec-
correlates with declining renal function, tion of antenatal hydronephrosis.
and the need for pyeloplasty. • Fetal hydronephrosis (dilatation of the renal
– The presence of symptoms including pain, pelvis with or without dilation of the renal
palpable renal mass or recurrent febrile UTI. calyces) is a common, readily diagnosed find-
– The presence of large anteroposterior ing on antenatal ultrasound examination and
diameter of renal pelvis exceeding can be detected as early as the 12th–14th week
20–30 mm predicts the need for surgery in of gestation.
50–55 % patients. • Although antenatal hydronephrosis is most
– Surgery allows preservation of renal func- often transient or clinically insignificant, uri-
tion in the majority of patients. nary tract obstruction or vesicoureteral reflux
– Predictors of unsatisfactory outcome (VUR) are important causes that should be
include baseline renal differential function diagnosed soon after birth because they may
<30 % and anteroposterior diameter of result in renal impairment or cause further
renal pelvis >50 mm with dilated calyces. renal damage.
• Antibiotic Prophylaxis • The risk of significant renal and urinary tract
– While there is increased risk of UTI, there is abnormality in those with hydronephrosis
lack of evidence that antibiotic prophylaxis increases with:
– The severity of hydronephrosis • Ultrasonography should be performed early,

– Persistence of hydronephrosis into the third within 24–48 h of birth for neonates with:
trimester – Suspected posterior urethral valves
– Bilateral involvement – Oligohydramnios
– The presence of oligohydramnios – Severe bilateral hydronephrosis
• Once fetal hydronephrosis is detected, the fol- – Severe hydronephrosis in a solitary kidney
lowing parameters need to be evaluated using
ultrasonography:
– Severity of hydronephrosis Pathological Causes of Antenatally
– Whether hydronephrosis is unilateral or Diagnosed Hydronephrosis
bilateral • Isolated Unilateral hydronephrosis
– Dilatation of the ureter – PUJ
• The risk of postnatal renal pathological • Unilateral hydronephrosis with
changes correlates with the degree of antena- hydroureter
tal hydronephrosis as follows: – Uretro-esical junction obstruction
– The risk for those with mild hydronephro- – Uretrocele
sis is 12 % – Vesicoueteric reflux
– The risk for those with moderate hydrone- – Posterior urethral valve
phrosis is 45 % • Isolated bilateral hydronephrosis
– The risk for those with severe hydrone- – Bilateral PUJ
phrosis is 88 % • Bilateral hydronephrosis with
• The severity of antenatal hydronephrosis cor- hydroureter
relates positively with: – Bilateral uretro-vesical obstruction
– Persistent postnatal hydronephrosis – Bilateral vesicoureteric reflux
– The need for surgical intervention – Posterior urethral valve
– The risk of UTI – Bilateral uretrocele
• Grading the severity of antenatal hydrone- – Urethral stricture
phrosis is important as this enables identifica-
tion of infants that require close follow-up.
• About 88 % of mild antenatal hydronephrosis
resolve in utero or in the neonatal period. • In all other cases, the ultrasound should be
• It has been estimated that one in three neo- performed preferably within 3–7 days, or
nates with moderate to severe hydronephrosis before hospital discharge.
persisting in the third trimester required post- • A single ultrasound in the first few days of life
natal surgery. might not detect all abnormalities of the kid-
• Hence, an ultrasound in the third trimester is neys or urinary tract, due to low urine flow
valuable for identifying fetuses that require secondary to dehydration and low glomerular
postnatal evaluation, follow up and possibly filtration rate. An ultrasound at 6 weeks is
surgery. more sensitive and specific for obstruction,
• A systematic review concluded that: than that in the first week of life.
– 98 % of patients with SFU grade 1–2 or • Postnatal radiologic studies:
antero-posterior diameter (APD) of the – Postnatal radiologic evaluation of a new-
renal pelvis <12 mm resolved. born with antenatal hydronephrosis begins
– 51 % of patients with APD >12 mm or SFU with an ultrasonography examination.
3–4 resolved. – The timing of ultrasonography and the
• All newborns with history of antenatal hydro- need for other studies depend on the sever-
nephrosis should have postnatal ultrasound ity of postnatal hydronephrosis and whether
examination within the first week of life.
2.8 Antenatal Hydronephrosis 67
there is bilateral involvement or an affected • It is usually ordered after a VCUG has

solitary kidney. demonstrated no vesicoureteral reflux.
– The timing of the study depends on the • It measures the drainage time from the
severity of the antenatal hydronephrosis. renal pelvis and assesses total and individ-
• In general, examination should be avoided ual kidney function.
in the first 2 days after birth because hydro- • The preferred radioisotope is technetium
nephrosis may not be detected because of Tc 99m-mercaptoacetyltriglycine (Tc99m
extracellular fluid shifts that underestimate MAG3), which is taken up by the renal cor-
the degree of hydronephrosis. tex, filtered across the glomerular base-
• However, infants with bilateral hydrone- ment membrane to the renal tubules, and
phrosis and those with a severe hydrone- excreted into the renal pelvis and urinary
phrotic solitary kidney require urgent tract.
evaluation on the first or second postna- • The management of infants with antenatal
tal day because of the increased likeli- hydronephrosis depends on:
hood of significant disease and a possible – Confirmation of persistent postnatal
need for early surgical intervention. hydronephrosis
• For those with unilateral hydronephro- – The severity of hydronephrosis: Fetuses
sis without antenatal bladder pathology, with a renal pelvic diameter greater than
performing postnatal sonography 15 mm during the third trimester are at the
1–4 weeks after birth is recommended. greatest risk for significant renal disease
– A voiding cystourethrography (VCUG) is – Whether hydronephrosis is bilateral or
performed to detect VUR and, in boys, to unilateral
evaluate the posterior urethra. – Whether hydronephrosis is in a solitary
kidney or not
• Bilateral hydronephrosis:
– Infants with severe bilateral antenatal
Postnatal Hydronephrosisultrasound
hydronephrosis and/or bladder distension
Evaluation
are at increased likelihood of having sig-
• The severity of hydronephrosis postna-
nificant disease.
tally is determined by a renal ultrasound
– These infants and those with a severe
performed after 48 h of life in a full term
hydronephrotic solitary kidney should be
infant and is based on anterior posterior
evaluated initially by ultrasonography on
pelvic diameter as follows:
the first postnatal day.
– <7 mm should be considered normal
– Bilateral hydronephrosis suggests an
– 7–8 mm: Mild hydronephrosis
obstructive process at the level of or distal
– 9–15 mm: Moderate hydronephrosis
to the bladder, such as uretrovesical
– >15 mm: Severe hydronephrosis.
obstruction, ureterocele or posterior ure-
These infants are at the greatest risk
thral valves (PUV) in a male infant, which
for significant renal disease, which
can be associated with impaired renal func-
requires surgical correction.
tion and ongoing renal injury.
– If postnatal ultrasonography demonstrates
persistent hydronephrosis, voiding cysto-
– Diuretic renography: urethrography (VCUG) should be per-
• This is used to diagnose urinary tract formed. In male infants, the posterior
obstruction in infants with persistent urethra should be fully evaluated to detect
hydronephrosis. possible PUVs.
– Infants with mild or moderate hydrone- phy findings or in those with mild
phrosis can be evaluated after 7 days hydronephrosis.
of life. – It was found that infants with high-grade
• Severe unilateral hydronephrosis: hydronephrosis receiving continuous anti-
– In newborns with severe antenatal unilat- biotic prophylaxis had significantly lower
eral hydronephrosis (renal pelvic diameter urinary tract infections when compared to
>15 mm in the third trimester), ultrasonog- those who did not receive prophylactic
raphy should be performed after age 48 h antibiotics (14.6 % vs 28.9 %).
and within the first 2 weeks of life). – This however is not the case for infants
• Moderate and mild unilateral hydronephrosis: with low-grade hydronephrosis were the
– In newborns with less severe antenatal uni- frequency of urinary tract infections were
lateral hydronephrosis (renal pelvic diam- similar (2.2 % vs. 2.8 %).
eter <15 mm during third trimester), – Other indications for prophylactic antibiot-
ultrasonography can be performed after ics include:
age 7 days to see whether the hydronephro- • The presence of ureteral dilation
sis has persisted postnatally. • Associated high-grade VUR
– Moderate hydronephrosis (renal pelvic • Ureterovesical junction obstruction
diameters between 10 and 15 mm) resolves – In patients with low-grade hydronephrosis
by age 18 months in most cases. Resolution (SFU grades I and II), there was no differ-
was defined as renal pelvic diameter ence in the rate of UTI between patients
≤5 mm on two consecutive ultrasounds. treated with continuous antibiotic prophy-
• Antibiotic prophylaxis: laxis and those who were not treated.
– The frequency of urinary tract infections – Patients with high-grade hydronephrosis
has been reported to be higher in children (SFU grades III and IV) who received con-
with prenatally diagnosed hydronephrosis tinuous antibiotic prophylaxis had a lower
when compared with the general pediatric rate of UTI compared with those who were
population. not treated with antibiotics.
– The risk of urinary tract infection rises if – Infants with persistent severe postnatal
there is an underlying urologic abnormal- hydronephrosis should have a VCUG to
ity, such as VUR or obstructive uropathy. detect VUR.
– The risk of urinary tract infection is greater • VUR accounts for approximately 9 % of
in girls than boys. cases of antenatal hydronephrosis, but it
– Infants with severe hydronephrosis are at is more common and severe in infants
greater risk for an underlying urologic with persistent postnatal hydronephro-
abnormality and should receive antibiotic sis (13–30 %).
prophylaxis after delivery until the diagno- • Infants who have VUR demonstrated on
sis of VUR or obstructive uropathy is VCUG should remain on antibiotic
excluded. prophylaxis.
– Children with mild or moderate hydrone- • If the VCUG does not show reflux, anti-
phrosis confirmed postnatally should also biotics are discontinued.
receive antibiotic prophylaxis (amoxicillin, • Surgical management:
12–25 mg/kg given orally per day) until the – The specific treatment of an infant with
diagnosis of VUR has been made or hydronephrosis and hydroureter depends
eliminated. on the etiology.
– Antibiotic prophylaxis is not indicated in – There is no good evidence to support that
infants with normal postnatal ultrasonogra- antenatal surgery in fetuses with sono-
Further Reading 69
graphic findings consistent with urinary 2. Coplen DE. Prenatal intervention for hydronephrosis.
tract obstruction improves renal outcome. J Urol. 1997;157(6):2270–7.
3. Estrada CR, Peters CA, Retik AB, Nguyen
– Signs of infection within the obstructed HT. Vesicoureteral reflux and urinary tract infection in
system warrant urgent intervention because children with a history of prenatal hydronephrosis –
infection with hydronephrosis may prog- should voiding cystourethrography be performed in
ress rapidly to sepsis. cases of postnatally persistent grade II hydronephro-
sis? J Urol. 2009;181(2):801–6.
– Bilateral Hydronephrosis with or without 4. Gordon I. Diuretic renography in infants with prenatal
hydroureter and hydronephrosis in a solitary unilateral hydronephrosis: an explanation for the con-
kidney calls for early evaluation and possi- troversy about poor drainage. BJU Int.
ble surgical intervention. 2001;87(6):551–5.
5. Gordon I, Dhillon HK, Gatanash H, Peters
– Urethral catheterization is important to AM. Antenatal diagnosis of pelvic hydronephrosis:
help rule out a lower urinary tract cause for assessment of renal function and drainage as a guide
hydronephrosis and hydroureter. to management. J Nucl Med. 1991;32(9):1649–54.
– Difficulty in passing a Foley catheter may 6. Grattan-Smith JD, Little SB, Jones RA. MR urogra-
phy evaluation of obstructive uropathy. Pediatr
suggest urethral stricture or bladder neck Radiol. 2008;38 Suppl 1:S49–69.
contracture. 7. Josephson S. Antenatally detected pelvi-ureteric junc-
– A percutaneous nephrostomy tube: tion obstruction: concerns about conservative man-
• This is useful in confirming and locating agement. BJU Int. 2000;85(7):973.
8. Koff SA. Postnatal management of antenatal hydrone-
the site of obstruction. phrosis using an observational approach. Urology.
• It is also useful in draining the obstructed 2000;55(5):609–11.
kidney and reliving the pressure on the 9. Mamì C, Paolata A, Palmara A, et al. Outcome and
renal parenchyma. management of isolated moderate renal pelvis dilata-
tion detected at postnatal screening. Pediatr Nephrol.
• It is also a useful measure to drain the 2009;24(10):2005–8.
kidney and buy time for the infant to 10. Sidhu G, Beyene J, Rosenblum ND. Outcome of iso-
grow in preparation for surgical lated antenatal hydronephrosis: a systematic review
intervention. and meta-analysis. Pediatr Nephrol. 2006;21:218–24.
11. Taylor Jr A, Clark S, Ball T. Comparison of Tc-99 m
• Add to this the fact that the ureter in MAG3 and Tc-99 m DTPA scintigraphy in neonates.
those patients with pelviureteric junc- Clin Nucl Med. 1994;19(7):575–80.
tion obstruction is small which makes it 12. Ulman I, Jayanthi VR, Koff SA. The long-term fol-
difficult to reconstruct the PUJ. low-up of newborns with severe unilateral hydrone-
phrosis initially treated nonoperatively. J Urol.
2000;164(3 Suppl 1):787–9.
13. Woodward M, Frank D. Postnatal management of
antenatal hydronephrosis. BJU Int. 2002;89(2):
Further Reading 149–56.
1. Chung S, Majd M, Rushton HG, Belman AB. Diuretic

renography in the evaluation of neonatal hydrone-
phrosis: is it reliable? J Urol. 1993;150(2 Pt
2):765–8.
Pelviureteric Junction (PUJ)
Obstruction 3
3.1 Introduction • PUJ obstruction occurs more on the left side than
on the right. The left kidney is affected in 67 % of
• Pelviuureteric junction (PUJ) obstruction is a cases and the right kidney in 33 % of the cases.
partial or complete blockage of the flow of urine • Bilateral PUJ obstruction is seen in about
from the renal pelvis into the ureter (Fig. 3.1). 10 % of the cases. Bilateral PUJ obstruction
• This results in accumulation of the urine in the (synchronous and asynchronous) is seen in
renal pelvis leading to its dilatation and back 10–40 % of infants <6 months.
pressure on the renal parenchyma leading to • Less than 5 % of patients with bilateral PUJ
progressive renal damage and deterioration. require bilateral repair because of spontane-
• PUJ obstruction is the most common cause of ous resolution in a significant number of
antenatally detected hydronephrosis and the most cases.
common cause of pediatric hydronephrosis. • With the current routine use of antenatal ultra-
• Ultrasonography reveals fetal upper urinary sound, most cases of congenital pelviureteric
tract dilatation in approximately 1 in 100 junction obstruction are diagnosed antenatally.
pregnancies; however, only 1 in 500 are later • PUJ obstruction may be diagnosed at any age.
diagnosed with significant urologic problems. – Some of these cases may be asymptomatic
• PUJ obstruction is found in approximately discovered incidentally during evaluation
50 % of patients diagnosed with antenatal of some other unrelated problem.
hydronephrosis. – PUJ may be identified during the investiga-
• The reported incidence of PUJ obstruction is tion of intermittent flank or abdominal
1 in 500 live births. Others report the esti- pain, urinary tract infection, hematuria.
mated incidence of PUJ obstruction as 1 per – Symptomatic cases may present with inter-
1,000–2,000 live newborns. mittent flank or abdominal pain that is
• The widespread use of antenatal ultrasonogra- made worse by drinking large amounts of
phy has contributed to an increase in the num- fluids or they may present with an abdomi-
ber and earlier diagnosis of hydronephrosis. nal or flank swelling.
• PUJ obstruction is commonly seen in infants • The cause is usually a congenital abnormality
and children and less commonly in adults. in the pelviureteric junction leading to its
• PUJ obstruction is found more commonly in narrowing.
boys than in girls. The male-to-female ratio of • Other causes of intrinsic PUJ obstruction
UPJ obstruction is 3–4:1. include:

72 3 Pelviureteric Junction (PUJ) Obstruction
KIDNEY
PARENCHYMA
RENAL
PELVIS
DILATED SITE OF
CALYCES PUJ
Fig. 3.1 Diagrammatic representation of PUJ obstruction (Note the dilated renal pelvis and calyces of the kidney and
the area of narrowing that usually causes partial obstruction to the flow of urine from the renal pelvis to the ureter)
– Valvular mucosal folds – Horseshoe kidney

– Persistent fetal ureteral convolutions – Ectopic kidney
– Ureteral polyps – Vesicoureteral reflux (up to 40 %)
• In about 10 % of children with PUJ obstruc- • The degree of obstruction is variable ranging
tion, an aberrant or accessory renal artery or from mild to severe.
arterial branch may cross the lower pole of the • Mild degrees of PUJ obstruction do not require
kidney, resulting in compression of the PUJ any surgical treatment, and these patients can
and blockage of urinary flow. be followed up hoping for complete spontane-
• In some cases, the obstruction may be acquired ous relive of obstruction.
following injury to the pelviureteric junction • Symptomatic patients and those with impaired
leading to its narrowing. This is usually renal function require surgical intervention to
secondary to inflammation related to a stone preserve the remaining function of the
stuck at the junction. kidney.
• PUJ obstruction is known to be associated • The first reconstruction of an obstructed kidney
with other urological anomalies and these was made in the late 1800s by Trendelenburg.
include: • In 1936, Foley described the YV-plasty to
– Renal dysplasia repair PUJ.
– Contralateral multicystic dysplastic kidney • In 1946, Anderson and Hynes described their
– Contralateral renal agenesis operation to treat PUJ obstruction. This is now
– Duplicated renal collecting system, in the standard operation used to repair PUJ
which case the lower pole system is usually obstruction and bear their name (The
the obstructed segment Anderson-Hynes dismembered pyeloplasty).
3.2 Embryology muscles movement and disrupt peristalsis

propagation across the PUJ. The end result is
• The ureter develops from the ureteral bud. a narrow but structurally patent lumen at the
• It extends upward towards the developing PUJ which in the presence of high urine vol-
kidney. ume cannot efficiently empty. This is sup-
• Induction of the metanephric blastema has ported by the followings:
been thought to be mediated by the ureteral – The findings of rearrangement and widely
bud through several factors including: separated smooth muscle cells
– Transcription factors such a Pax-2 – The findings of excessive collagen fibers
– Growth factors such as c-ret, kdn-1, and – The findings of increased elastin in the
wt1 adventitia
– Transforming growth factor β (TGFβ). – The findings of diminution of nerve termi-
• Embryologically, the pelvi-ureteric junction nals and nerves at the stenotic portion.
forms usually around the fifth week of intra-
uterine life.
• At around the 10th–12th weeks of intra- 3.3 Pathophysiology
uterine life, the initial solid tubular lumen of
the ureter becomes reanalyzed. • The drainage of urine from the renal pelvis to
• It has been suggested that the ureteropelvic the ureter depends on several factors.
and ureterovesical portions of the ureter are – Pressure within the renal pelvis is deter-
the last to canalize. mined by the volume of urine produced
• Failure of canalization or partial canalization – The internal diameter of the PUJ and col-
is thought to be the main embryological expla- lecting system
nation of a PUJ obstruction. – The compliance of renal pelvis
• Another theory suggests arrest of ureteral wall – The peristaltic activity of the ureter
musculature development leading to the per- • In response to the increased urinary volume
sistence of an aperistaltic segment at the PUJ and pressure, the renal pelvis dilates.
level leading to partial obstruction. • The effect of this on the renal parenchyma
• Another theory suggests improper innervation may be quite variable.
with diminished synaptic vesicles at the PUJ • Sometimes and despite of massive dilation of
which may play a role in the development of the renal pelvis, preservation of renal function
PUJ obstruction. This was supported by the may occur.
findings of decreased amounts of the several • A pressure-dependent flow:
factors in the resected specimens of PUJ. These – This is seen in those with intrinsic obstruc-
include: tion where at low urinary flow rates, no
– Protein gene product (PGP) 9.5 (a general obstruction exists; but as the urinary flow
neuronal marker) rate increases, urinary stasis will develop
– S-100 protein (a nerve supporting cell leading to dilatation of the renal pelvis.
marker) • A volume-dependent flow:
– Synaptophysin (a synapse vesical marker) – This is seen in those with extrinsic
– Nerve growth factor receptor obstruction usually caused by aberrant
• Early in the embryological development, the vessels. There is a normal urine flow
proximal ureter is folded on itself and which is impeded only after a definite
persistence of the unfolding may contribute to amount of urine is collected in the renal
the kinked appearance of the proximal ureter. pelvis.
• The most attractive theory is that the PUJ – Patients with extrinsic obstructions tend to
obstruction is secondary to muscular disconti- present late in childhood, with intermittent
nuity. This disrupts the coordinated smooth abdominal or flank pain.
– The degree of renal damage generally is 3.4 Etiology of PUJ Obstruction

less than that of intrinsic obstruction
because the pressure damage is only evi- • There are several causes of PUJ obstruction
dent intermittently. and these can be divided into two groups, pri-
• This obstructive nephropathy is progressive if mary and secondary causes.
the PUJ obstruction is not relived and this • Primary causes include (Figs. 3.4 and 3.5):
manifest in progressive deterioration of the – Intrinsic obstruction from stenosis at the
renal function (Figs. 3.2 and 3.3). PUJ due to scarring of ureteral valves.
• Sometimes, the obstructive nephropathy will – An abnormal or high insertion of the ureter
progress and becomes irreversible in spite of into the renal pelvis. This is controversial
relive of the PUJ obstruction. ad many consider this a secondary phe-
• There is also activation of the renin- nomenon to obstruction.
angiotensin system and administration of the – Ureteral hypoplasia may result in abnormal
angiotensin-converting enzyme (ACE) inhibi- peristalsis through the PUJ.
tors has been shown to maintain renal blood – Asymmetry of ureteral wall musculature
flow and prevent the histologic changes of may inhibit the natural peristaltic emptying
glomerulosclerosis. of the renal pelvis into the ureter.
• The long-term effects of PUJ obstruction on • Secondary causes include (Figs. 3.6, 3.7, 3.8,
the kidney are quite variable and depend on 3.9, 3.10, 3.11 and 3.12):
several factors including: – Crossing lower-pole renal vessel(s).
– The variability in the degree of – Fibrous bands
obstruction – Kinks
– The timing of the obstruction – Horseshoe or pelvic kidney
– The ability of the renal pelvis and renal col- – Duplex collecting systems
lecting system and renal parenchyma to – Rotational abnormalities of the kidney
adjust to the changes associated with – Renal hypermobility can cause intermittent
obstruction. obstruction that is solely dependent on the
– Early PUJ obstruction causes severe mal- position of the kidney relative to the ureter.
formation of the kidney (dysplasia), – Secondary PUJ obstruction can be caused
whereas late occurring PUJ obstruction by prior surgical intervention to treat other
may not affect the kidney as severely. renal disorders (e.g., renal stone)
Figs. 3.2 and 3.3 Abdominal CT-scan in two children pelvis and pressure on the renal parenchyma while in the
with PUJ obstruction (Note the sever renal atrophy in the second one there is relative preservation of the renal
first CT as a result of progressive dilatation of the renal parenchyma)
3.4 Etiology of PUJ Obstruction 75
Figs. 3.4 and 3.5 Contrast studies through a nephros- inserted ureter in the left picture. Many feel that the high
tomy tube for two children with PUJ obstruction (Note the insertion of the ureter is secondary to the dilated renal pel-
normally inserted ureter in the right picture and the highly vis rather the primary cause of PUJ obstruction)
KINKED
URETER
KINKED
URETER
Figs. 3.6 and 3.7 Contrast studies through a nephrostomy tube in two children with PUJ obstruction (Note the kinked
ureters in both but it is difficult to decide whether this is the cause or it is secondary to PUJ obstruction)
– Failed repair of a primary PUJ obstruction. – Ureteral-wall and periureteral scar forma-
– Inflammation at the PUJ secondary to an tion as a result of inflammation or prior sur-
obstructing stone. gical repair.
DILATED RENAL PELVIS

DILATED RENAL PELVIS
URETER
Figs. 3.8, 3.9, and 3.10 A contrast study and intraoperative photographs of a child with a hydronephrotic pelvic
kidney secondary to PUJ obstruction that was also malrotated
• Aberrant polar vessels may also cause com-

pression and obstruction of the PUJ. 3.5 Clinical Features
• The end result of PUJ obstruction depends on
the severity of obstruction. This will lead to • PUJ obstruction is the most common cause of
the following changes: neonatal and antenatal hydronephrosis, occur-
– Impaired urinary drainage ring in 1 per 1,000–1,500 live births.
– Elevated intrarenal back pressure • The presentation of PUJ obstruction is also
– Dilatation of the renal pelvis and collecting variable.
system, and hydronephrosis • Neonates with PUJ obstruction are usually
– Back pressure on the renal parenchyma asymptomatic and the majority present with
– Progressive renal damage and renal hydronephrosis that was diagnosed in utero by
deterioration an antenatal ultrasound.
ABERRANT
POLAR VESSEL
URETER
DIVIDED
URETER
DILATED RENAL
PELVIS
Figs. 3.11 and 3.12 Intraoperative photographs show- photograph. Note also the associated hydronephrosis fol-
ing hydronephrosis secondary to an aberrant lower polar lowing division of the ureter
vessel. Note the vessel compressing the ureter in the upper
• Prior to the use of prenatal ultrasonography, • Renal failure is an unusual presentation,

most patients with PUJ obstruction present with: and occurs in infants with a single
– Pain obstructed kidney or with bilateral
– Hematuria severe hydronephrosis.
– Urinary tract infection • Older children may present with:
– Failure to thrive – The presentation of patients with PUJ is vari-
– A palpable mass able depending on the severity of obstruction.
• Currently, with the availability and routine use – Intermittent back pain, flank pain or
of prenatal ultrasonography, urologic abdominal pain
abnormalities including PUJ obstruction are – The pain may worsen during brisk diuresis
being diagnosed earlier and more frequently. – Abdominal pain may be accompanied by
• 50 % of patients diagnosed with antenatal nausea and vomiting
hydronephrosis are eventually diagnosed with – A detailed history may reveal that the pain
PUJ obstruction upon further workup. correlates with periods of increased fluid
• Fetal and neonatal hydronephrosis: intake or ingestion of a food with diuretic
– Most cases of PUJ obstruction are diag- properties (i.e. Dietl’s crisis).
nosed antenatally during routine antenatal – Urinary tract infection
ultrasound. – A flank mass representing the hydrone-
– These cases are confirmed by postnatal phrotic kidney
ultrasound. – The enlarged kidney is vulnerable to trau-
– Newborns may present with: matic injury (Figs. 3.13, 3.14 and 3.15)
• A palpable abdominal mass caused by – Hematuria
an enlarged obstructed kidney. – Renal calculi
• Urinary tract infection – Hypertension
• Hematuria – An incidental finding on abdominal ultra-
• Failure to thrive sound evaluation
Figs. 3.13, 3.14, and 3.15 Abdominal CT-scans showing trauma and rupture of a hydronephrotic kidney in a child
with PUJ obstruction
• Initially, most children diagnosed to have PUJ • Earlier postnatal ultrasound (24–48 h) is per-
obstruction are treated conservatively and formed for those with severe PUJ obstruction.
monitored closely. – Those with very large renal pelvis
• Surgical intervention is indicated in symptom- – Those with bilateral hydronephrosis
atic patients and those with significantly – Those with solitary kidney
impaired renal drainage and decreased renal – Those with PUJ obstruction and
function. oligohydramnios
• The presence of significant hydronephrosis on • The most widely used grading system of the
antenatal ultrasound is based on the followings: severity of hydronephrosis on ultrasonogra-
– The anteroposterior diameter of the renal phy after birth is SFU (Society for Fetal
pelvis is more than 10 mm. Urology) system, rather than the anteroposte-
– The ratio of the renal pelvis to the antero- rior diameter of the renal pelvis.
posterior kidney is more than 0.3. • The SFU grading system for hydronephrosis
– Evidence of caliectasis is present after is as follows :
24 weeks of gestation. – Grade 0:
• A follow-up postnatal ultrasound should be • No hydronephrosis, intact central renal
performed 36–48 h after birth to avoid the complex seen on ultrasonography
transient neonatal dehydration. – Grade 1:
3.6 Diagnosis and Investigations 79
• Only renal pelvis visualized, dilated

pelvis on ultrasonography, no The SFU Grading System for
caliectasis Hydronephrosis
– Grade 2: • Grade 0:
• Moderately dilated renal pelvis and a – No hydronephrosis, intact central renal
few calyces complex seen on ultrasonography
– Grade 3: • Grade 1:
• Hydronephrosis with nearly all calyces – Only renal pelvis visualized, dilated pel-
seen, large renal pelvis without paren- vis on ultrasonography, no caliectasis
chymal thinning • Grade 2:
– Grade 4: – Moderately dilated renal pelvis and a
• Severe dilatation of renal pelvis and few calyces
calyces with accompanying parenchy- • Grade 3:
mal atrophy or thinning – Hydronephrosis with nearly all caly-
• Approximately 20 % of antenatally diagnosed ces seen, large renal pelvis without
hydronephroses are not found on postnatal parenchymal thinning
ultrasound. • Grade 4:
• PUJ obstruction is known to be associated – Severe dilatation of renal pelvis and
with other types of congenital abnormality. calyces with accompanying paren-
This is seen in almost 50 % of patients. chymal atrophy or thinning
• PUJ obstruction is bilateral in about 10 % of
patients (Figs. 3.16, 3.17 and 3.18).
• About 10 % of patients with PUJ obstruction
have ipsilateral vesicoureteral reflux and to
detect this, a voiding cystourethrogram
should be part of the work-up of these 3.6 Diagnosis and Investigations
patients.
• There are also reports of coexisting PUJ • Prenatal evaluation:
obstruction and uretero-vesical junction – Prenatal ultrasound is widely used to diag-
obstruction. In these cases, the uretero-vesical nose fetal abnormalities.
obstruction is usually mild and PUJ obstruc- – Among these abnormalities is PUJ
tion should be treated first. obstruction.
• Duplication anomalies usually cause PUJ – Prenatal ultrasound evaluation should
obstruction at the lower poles and the possibil- include the followings:
ity of vesicoureteral reflux should be rolled • Amniotic fluid volume to rule out
out. oligohydramnios
• Rarely, the PUJ may be so severe leading to • Bladder volume
massive dilation of the renal collecting system • Kidney size
and these patients may present with a palpable • Anteroposterior diameter of the renal
flank mass. This however is a rare and unusual pelvis
presentation of PUJ at present. • Other associated abnormalities
• PUJ obstruction is often associated with other – Functionally significant hydronephrosis
congenital anomalies, including: can be determined when:
– Anorectal malformations • The anteroposterior diameter of the
– Contralateral multicystic kidney renal pelvis is more than 10 mm.
– Congenital heart disease • The ratio of the renal pelvis to the antero-
– VATER (vertebra, anus, trachea, esopha- posterior kidney size is more than 0.3.
geal, renal) syndrome • There is evidence of caliectasis after
– Esophageal atresia 24 weeks of gestation.
Figs. 3.16, 3.17, and 3.18 Abdominal CT-scan and intravenous urography showing bilateral hydronephrosis second-
ary to PUJ obstruction
• Patients with PUJ obstruction diagnosed by that will underestimate the degree of
prenatal ultrasound should have a postnatal hydronephrosis.
ultrasound. The timing of ultrasound is vari- • Therefore, in unilateral disease, ultrasonography
able and depends on the severity of the PUJ should be performed at least after 48 h of life.
obstruction. • These patients should also be placed on pro-
• In general, however, ultrasound examination phylactic antibiotics (amoxicillin 15 mg/kg)
should be avoided in the first 2 days after to prevent urinary tract infections.
birth, because hydronephrosis may not be • Other investigations include:
detected because of extracellular fluid shifts – Complete blood count
– Urine analysis and culture – A plain abdominal x-ray may also show radi-
– Serum electrolytes, BUN and creatinine opaque stones complicating PUJ obstruction.
– Plain abdominal radiograph • Abdominal ultrasound (Figs. 3.20 and 3.21):
– Abdominal ultrasound – Renal ultrasound will show a dilated renal
– Abdominal CT-scan pelvis with a collapsed non-dilated ureter.
– Abdominal MRI – Renal ultrasound is also important to mea-
– A nuclear renal scan can sure the size of the renal pelvis and it is use-
– Intravenous urography ful for follow-p to monitor changes in the
– Voiding cystourethrography size of the renal pelvis.
– Percutaneous nephrostography – Ultrasound can also help determine the size
– Cystoscopy and retrograde pyelography of the kidney, the size of renal and the
– A Whitaker antegrade pressure-flow study thickness of renal parenchyma.
• Serum electrolytes, BUN and creatinine are – Ultrasound is also important to detect other
important to measure renal function especially associated urological abnormalities.
in those with bilateral disease. – Duplex Doppler ultrasonography can be
• Urine analysis and culture are important to used to assess intrarenal vasculature and
roll out associated urinary tract infection espe- determine the resistive index.
cially in asymptomatic patients. • Normal kidneys reliably demonstrate
• Abdominal radiograph (Fig. 3.19): resistive indices less than 0.7, and
– A plain abdominal x-ray may show a soft obstructed kidneys show higher values.
tissue density secondary to a hydrone- • This is especially reliable in the preopera-
phrotic kidney. tive diagnosis of aberrant-accessory blood
vessels associated with PUJ obstruction.
– Renal ultrasound is a relatively cheap
investigation, devoid of radiation and can
easily be repeated.
• Intravenous urography (Figs. 3.22, 3.23 and
3.24):
– Historically, intravenous pyelography
(IVU) was used to evaluate patients with
possible PUJ obstruction.
– The administration of frusemide helps
exclude a ‘baggy pelvis’.
– Currently, intravenous urography is
replaced by other less invasive and more
informative investigations.
– Intravenous urography has the risk of radi-
ation exposure and contrast media includ-
ing nephrotoxicity and anaphylactic
reactions.
• The diagnosis of intermittent UPJ obstruction
is confirmed if hydronephrosis is present
when the child is symptomatic, and resolves
when the child is well. A diuretic renal scan
will document baseline renal function and
may also provoke symptoms during the
Fig. 3.19 Abdominal radiograph showing a soft tissue diuretic phase of the study, which confirms the
density on the left side in a child with severe left PUJ
diagnosis.
obstruction
Figs. 3.20 and 3.21 Andominal ultrasound showing severe hydronephrosis secndary to PUJ obstruction
• Abdominal CT-scan (Figs. 3.25, 3.26, 3.27, – In children, this study has several
3.28 and 3.29): advantages:
– Abdominal CT-urography is very useful in • No radiation exposure.
establishing the severity of PUJ obstruction • Excellent anatomical and functional
including the renal parenchymal volume. details.
– Establishing the anatomy of PUJ obstruction. • It provides details of renal vasculature,
– Identification of an intrinsic cause or high- renal pelvis anatomy, location of cross-
insertion PUJ. ing vessels, renal cortical thickness and
– Demonstrating crossing vessels and their scarring.
relationship to the ureter of the PUJ. – The disadvantage of this investigation is
– The localization of these vessels and their that it is not readily available and require
possible contribution to renal obstruction is general anesthesia.
important for surgical planning and the – Contrast-enhanced magnetic resonance angi-
most effective treatment modality. ography (MRA) was reported to have a sensi-
– If an endopyelotomy is planned, this infor- tivity of 85 %, a specificity of 80 %, and a
mation can guide the surgeon in directing positive predictive value of 0.8 for the diagno-
the endopyelotomy incision away from sis of aberrant and obstructing renal arteries.
crossing vessels. • Diuretic renography (Fig. 3.32):
– It is also useful in outlining the location of – A diuretic renal scan should be performed
secondary causes of PUJ obstruction includ- to quantify relative renal function and to
ing aberrant vessels, kinks, and adhesions. define the extent of obstruction.
– Spiral (helical) CT-scan is more useful as it – There are several isotope tracers that are
provides superior longitudinal resolution. used for diuretic renography including:
– Abdominal CT-scan requires sedation or • Mercaptotriglycylglycine (MAG-3)
general anesthesia in very small children and • Diethylenetriamine (DTPA)
also carries the risk of radiation exposure. • Dimercaptosuccinic acid (DMSA)
– Abdominal CT-scan has a sensitivity of • Technetium-99m-mercaptoacetyltriglycine
97 %, specificity of 92 %, and accuracy of (99m Tc-MAG3)
96 % in detecting crossing vessels associ- – This is the most noninvasive technique
ated with PUJ obstruction. used to determine the severity and func-
• Abdominal MRI (Figs. 3.30 and 3.31): tional significance of PUJ obstruction.
– Dynamic contrast-enhanced magnetic res- – The preferred radioisotope is technetium-
onance urography (MRU) is the latest 99m-mercaptoacetyltriglycine (99m Tc-
imaging modality used in assessing PUJ MAG3), which is taken up by the renal cortex,
obstruction. filtered across the glomerular basement mem-
Figs. 3.22, 3.23, and 3.24 Intravenous urography showing bilateral PUJ obstruction
brane to the renal tubules, and excreted into (99m Tc-DTPA), which, owing to the small
the renal pelvis and urinary tract. size of molecule, diffuses within both intra-
– MAG3 is another tracer that is mainly vascular and extravascular spaces, result-
intravascular and secreted by proximal ing in significant background activity.
renal tubules, with a small fraction being – The diuretic renography measures the
filtered by the glomeruli. drainage time from the renal pelvis (referred
– Another widely used tracer is technetium to as washout) and assesses total and each
99m diethylenetriamine penta-acetic acid individual kidney’s renal function.
Figs. 3.25, 3.26, and 3.27 Abdominal CT-scans show- almost complete renal atrophy where there is only a small
ing hydronephrosis secondary to PUJ obstruction (Note rim of renal parenchyma remaining while in the lower one
the very severe obstruction in the middle picture with the renal parenchyma is still preserved)
Figs. 3.28 and 3.29 Abdominal CT-scan showing bilateral hydronephrosis secondary to PUJ obstruction
Figs. 3.30 and 3.31 Abdominal MRI showing bilateral hydronephrosis secondary to PUJ obstruction (Note the thick-
ness of the renal parenchyma on the right side. It is thinned out as a result of severe obstruction and back pressure)
Fig. 3.32 A diuretic nephrogram of a child with a left PUJ obstruction
– The washout measurement correlates with indicates no obstruction, while impaired

the degree of obstruction. drainage or slow or no washout (T1/2
– The patency of the PUJ is determined by >20 min) indicates obstruction.
measuring the T1/2 (the time required for – Another important measurements in
50 % of the isotope to be excreted) on the diuretic renography is the estimate of dif-
wash-out curve. Rapid drainage (low T1/2) ferential renal function. This is considered
Figs. 3.33 and 3.34 Voiding cystourethrograms in two children with PUJ obstruction (Note the absence of VUR. Note
also the soft tissue density on the right side in the lower picture representing the enlarged right kidney)
significant when it is less than 40 %. other urologists use split function, compar-
Diuretic (Furosemide) Renogram is per- ing the function of the two kidneys, as a
formed to differentiate obstructive from means to identify patients for surgery.
nonobstructive hydronephrosis. – Renal isotope scan is also used to assess
– Sometimes an unusually high differential outcomes after surgical correction of PUJ
renal function can be seen on the affected obstruction.
kidney. This is attributed to an increase in • A voiding cystourethrography (VCUG)
single-nephron filtration or nephron (Figs. 3.33 and 3.34):
volume. – A voiding cystourethrography (VCUG) is
– Currently, a diuretic renal scan is important part of the work up of these patients.
to diagnose those with functionally signifi- – This is to rule out vesicoureteral reflux.
cant PUJ obstruction. The Reno graphic – Vesicoureteral reflux (VUR) has been found in
criteria include: as many as 40 % of children with PUJ obstruc-
• A flat or rising washout curve after tion but the reported incidence of VUR in asso-
diuretic with T 1/2 of greater than ciation with PUJ obstruction is about 10 %.
20 min and differential function of less – The VUR is usually mild and usually
than 40. resolve spontaneously.
• The differential function is important in • Retrograde/antegrade pyelography:
determining the need for intervention, – Retrograde pyelography was used to assess
especially in asymptomatic patients, the upper ureter and renal pelvis.
and in selecting the appropriate treat- – Retrograde or antegrade pyelography
ment (pyeloplasty vs nephrectomy). requires general anesthesia.
• Poorly functioning kidneys (<10 %) are – It is now mostly performed at the time of
often best treated with nephrectomy. surgical correction of the PUJ obstruction
– In general, a half-life greater than 20 min to to establish the exact site of obstruction.
clear the isotope from the kidney is consid- – A percutaneous nephrograohy (Figs. 3.35,
ered indicative of obstruction, although 3.36, 3.37 and 3.38):
Figs. 3.35, 3.36, 3.37, 3.38, and 3.39 Nephrostograms confirm the diagnosis and severity of PUJ but they are
showing unilateral and bilateral PUJ obstructions. useful for temporary drainage of the obstructed kidney to
Percutaneous nephrostograms are useful especially in refive the pressure from the renal parenchyma)
newborns with severe hydronephrosis (Note only they
• This can be diagnostic and also used to – When the radiological investigations are
temporary drain the kidney to decom- equivocal, a Whitaker antegrade pressure-
press the renal pelvis and relive the flow study may be performed to further
pressure on the renal parenchyma. evaluate for PUJ obstruction.
• This is valuable especially in newborns – This is done as follows:
with severe obstruction. The ureter is • A small-diameter nephrostomy tube
small in these patients which makes it is inserted percutaneously into the
difficult to reconstruct the PUJ and a kidney.
temporary nephrostomy will drain the • Dilute contrast medium is instilled, and
obstructing kidney and buy time. the intrarenal collecting system is
• Pressure flow studies: pressure-monitored.
• Under fluoroscopy, the PUJ is assessed nephrostomy tube to determine whether return
and drainage through this segment is of function will be sufficient.
evaluated. • Others consider this a non-functioning kidney
• High intrarenal pressures is indicative of and there is no point in inserting a nephros-
PUJ obstruction. tomy. Add to this the fact that nephrostomy is
• Low intrarenal pressures in the presence difficult to maintain in infants and children and
of hydronephrosis are consistent with it is known to be associated with bacteriuria.
normal variance. • Nephrectomy is indicated in those with a dif-
• The Whitaker test is a pressure flow ferential function <10 % and complicated by
study that has proven useful in equivo- hypertension or recurrent urinary tract
cal PUJ obstruction in children. infection.
• A catheter is introduced percutaneously • Surgical Therapy:
into the renal pelvis. The patency of the – Prolonged partial PUJ obstruction is dele-
PUJ is challenged fluid infusion via the terious to the newborn kidney and can be
catheter and simultaneously measuring reversed by early relief of the obstruction.
the intrapelvic pressure. – Spontaneous resolution of hydronephrosis
although well known, 15–33 % of patients
with asymptomatic neonatal hydronephro-
3.7 Management of Newborns sis show progressive ipsilateral renal dete-
with PUJ Obstruction rioration, and about one half of them never
regain the lost function by pyeloplasty.
• The timing of surgical correction of PUJ – There is a definite percentage of patients
obstruction in newborns is highly with PUJ obstruction treated conserva-
controversial. tively who will sustain irreversible renal
• Immediate surgery is not necessary for those damage that could have been prevented by
newborns with relatively preserved differen- early pyeloplasty.
tial renal function (>40 % of differential renal • Indications for surgical interventions in PUJ
function). obstruction:
• These patients can be observed safely nonop- – Unilateral PUJ obstruction with less than
eratively as in some of them the obstruction 40 % of differential renal function on
will resolve spontaneously. diuretic renograms.
• These patients should be covered with antibi- – Bilateral severe PUJ obstruction with renal
otic prophylaxis. parenchymal atrophy.
– The use of antibiotic prophylaxis in mild – Obstructive pattern on diuretic renograms
hydronephrosis is still controversial. with abdominal mass, urosepsis, or other
– Most authors advocate antibiotic prophy- symptoms.
laxis for those with moderate-to-severe – Recurrent UTI under antibiotic
hydronephrosis (SFU grade 3 or 4). prophylaxis.
• Urinary tract infection in these patients • A temporary percutaneous nephrostomy was
increases the chance of fibrosis and parenchy- advocated in newborns with severe hydrone-
mal damage. phrosis. The aims of this include (Figs. 3.40,
• Patients with renal function >40 % are moni- 3.41, 3.42 and 3.43):
tored with repeat renal scans at 3- to 6-month – To confirm the diagnosis and document the
and 12-month intervals, and surgery is per- severity of obstruction.
formed only if a clear deterioration in renal – To drain the obstructed kidney and relive
function is present. the pressure on the renal parenchyma.
• In cases in which the differential function is – Newborns and because of the partial PUJ
<10 %, some recommend the insertion of a obstruction have a small size ureter that
3.8 Treatment 89
Figs. 3.40, 3.41, 3.42, and 3.43 Percutaneous neph- obstruction and the extent of hydronephrosis. The neph-
rostograms showing unilateral and bilateral PUJ obstruc- rostomy is also useful for temporary drainage of the
tion in newborns and infants (Note the degree of obstructed kidney)
makes it difficult operatively to reconstruct 3.8 Treatment

the new PUJ and placing a temporary neph-
rostomy will time to decompress the kid- • The aims of treating patients with PUJ obstruc-
ney, increase the size of the ureter and tion are:
allow the child to grow. – Relive the obstruction
– Nephrostomy tubes are also known to be – Improve renal drainage
associated with complications including – Maintain or improve the renal function
sepsis, kinking and spontaneous • There is no evidence that prenatal intervention
dislodgment. in infants with either a single obstructed
kidney or bilateral involvement improves change in the degree of hydronephrosis

renal outcome. that may necessitate surgical intervention.
• Antenatal intervention however is recom- • Renal ultrasound evaluations are per-
mended in those with extremely severe PUJ formed every 3–4 months until the
obstruction and only be done in centers with child reaches 1 year of age, every
experienced surgeons as this may be associ- 6 months for the next 2 years, and then
ated with morbidity and fetal mortality. annually.
• Asymptomatic patients with PUJ obstruction: • If the renal ultrasound shows increasing
– The ultimate goal of management is to pre- hydronephrosis, a diuretic renogram is
serve renal function and avoid unnecessary repeated to detect any change in renal
surgery. function or confirm that the renal func-
– Managing asymptomatic patients is chal- tion is stable.
lenging, because the natural course of PUJ • If diuretic renogram shows deteriora-
obstruction is variable. tion of >10 % in the renal function on
– It appears that many patients with PUJ the affected side, or the relative renal
obstruction will have stable renal function function is <40 %, surgery is
and improvement in the degree of recommended.
hydronephrosis during long periods of • These studies are performed more fre-
observation. quently (every 2–3 months) if the rela-
– However, others will have deterioration of tive renal function is borderline, and
their renal function, and appear to benefit significant hydronephrosis is present.
from surgical repair of PUJ obstruction. – The problem is more complicated in those
– There is no reliable method to predict which with bilateral asymptomatic PUJ obstruc-
patients with asymptomatic PUJ obstruction as the relative renal function may not
tion, their kidney function will deteriorated be a reliable measure.
and whether the function of a kidney with – In these patients, glomerular filtration rate
PUJ obstruction will remain unaffected can be measured with serum creatinine
during the period of observation. and/or by renal scan. If renal function is
– As a result of this, there is controversy on significantly decreased, surgery is indi-
the role of watchful observation with sur- cated to relieve PUJ obstruction.
gical intervention only in those who – Antibiotic prophylaxis:
develop symptoms or if there is a • This has been recommended in these
decrease in renal function. This approach patients because urinary stasis is
may prevent unnecessary surgery in some believed to be a risk factor for urinary
asymptomatic patients with PUJ tract infection.
obstruction. • This is also controversial and does not
– Patients with PUJ obstruction are moni- appear that it is beneficial in children
tored closely with renal ultrasonography with PUJ obstruction especially those
and nuclear scans every 3–4 months. with mild PUJ obstruction.
– It is important to monitor the renal pelvic • There are those who advocate giving
dilatation with serial ultrasounds. This is antibiotic prophylaxis for patients with
important to assess: severe, grade IV hydronephrosis until
• Changes in renal pelvic dilatation the time of the voiding cystourethro-
• Renal parenchymal thickness gram (VCUG). If the VCUG does not
• The presence of scarring, and function. show vesicoureteral reflux, the prophy-
– Patients with asymptomatic PUJ obstruc- lactic antibiotics are discontinued.
tion should be monitored and followed-up • Others will give prophylaxis antibiotics
with serial renal ultrasounds to detect any for all patients with PUJ obstruction.
3.8 Treatment 91
• Children with PUJ obstruction who are symp- 40 %, and ongoing parenchymal thinning
tomatic require operative intervention. with or without contralateral compensatory
• Kidney stones sometimes develop in those hypertrophy.
with PUJ obstruction and these patients should – With progressive increase in the size of
be treated with open pyelolithotomy and renal pelvis on serial imaging.
pyeloplasty. – With bilateral PUJ obstruction and thin-
• Patients with PUJ obstruction who present ning of renal parenchyma.
with acute pyelonephritis are treated first with • There are several methods to treat PUJ
antibiotics. Surgical repair is performed when obstruction.
the infection has resolved but if pyelonephritis • Open surgical Therapy (Fig. 3.44):
does not respond to antibiotics, a temporary
percutaneous nephrostomy should be placed
to drain the kidney and relieve the Asymptomatic Patients with PUJ
obstruction. Obstruction
• Initially, most children with incomplete PUJ • Observation is appropriate for asymp-
obstruction are treated conservatively and tomatic patients with PUJ obstruction
monitored closely. and hydronephrosis that is mild to mod-
• Monitoring of these patients include serial erate in severity (i.e. Society of Fetal
renal ultrasonography and renal isotope scan. Urology [SFU] grade II to III).
• Surgical intervention is indicated in patients • These patients are followed-up with
with PUJ obstruction: ultrasound examination every 4 (Grade
– Who are symptomatic (pain, hypertension, III) to 6 (Grade II) months in the first
hematuria, secondary renal calculi, and year of life, then every 12–18 months
recurrent urinary tract infections). thereafter.
– With significantly impaired renal drainage • If there is an increase in the degree of
or poor renal growth hydronephrosis, a diuretic renogram is
– With deterioration of renal function (a performed.
serial loss in renal function >10 %). • If the affected kidney has <40 % of split
– With clearance half-time (T 1/2) greater renal function, or there is a serial loss
than 20 min, differential function less than
PUJ OBSTRUCTION
URETER DILATED RENAL

PELVIS
Fig. 3.44 An
intraoperative
photograph showing
hydronephrosis
secondary to PUJ
re-tubularized using the redundant renal

>10 % from a previous study, surgical pelvis.
intervention is recommended. – In 1946, Anderson and Hynes described
• Newborns who have persistent SFU their operation to treat PUJ obstruction.
grade IV hydronephrosis require closer The Anderson-Hynes dismembered
observation and frequent renal ultra- pyeloplasty is currently the most com-
sound follow-up. monly used procedure to repair PUJ
• In these patients, a diuretic renogram is obstruction.
performed at 6–8 weeks of age. – In children, the procedure of choice to treat
– If the hydronephrotic kidney has PUJ obstruction is an Anderson-Hynes dis-
decreased renal function (<40 % of membered pyeloplasty.
split renal function) compared with – The Anderson-Hynes dismembered pyelo-
its normal contralateral side, surgical plasty is particularly useful for those with
intervention is recommended. the high-insertion variant of PUJ
– If the hydronephrotic kidney have obstruction.
equal function compared with the
normal contralateral kidney, the renal
sonogram is repeated in 4–6 weeks. Indications for Surgery in PUJ Obstruction
If the sonogram shows improvement, • Symptomatic patients (flank pain, uri-
these patients are followed-up with nary tract infection, and renal stones).
serial renal ultrasounds at 3–4 month • Unilateral PUJ obstruction with <40 %
intervals. of differential renal function on diuretic
– Any worsening of the hydronephro- renograms or there is a serial loss in
sis calls for a diuretic renogram. renal function >10 %.
– If these serial sonograms show con- • Bilateral severe PUJ obstruction with
tinued SFU grade IV hydronephrosis renal parenchymal atrophy.
without substantial change from pre- • Obstructive pattern on diuretic reno-
vious studies: grams with abdominal mass, urosepsis,
• Continued observation and moni- or other symptoms (e.g., cyclic flank
toring including renal ultrasound pain, nausea, vomiting).
and diuretic renograms • Recurrent UTI in spite of antibiotic
• If the family prefer, surgical inter- prophylaxis.
vention is recommended. • Massive hydronephrosis (renal pelvis
diameter >4–5 cm.
• Parental preference in those who require
– In 1936, Foley introduced the YV-plasty frequent observation and invasive
for the correction of PUJ obstruction. testing.
– Culp and DeWeerd designed a spiral flap in
the dilated pelvis and used it to repair the
defect of the PUJ.
– The Foley Y-V plasty is used to treat PUJ
obstruction and those with the high-insertion Patients with renal function more than 40 %
variant but cannot be used in the presence of on the affected side are monitored with
apparent lower-pole vessel. repeat renal scans at 3- to 6-month and
– Spiral and vertical flaps (e.g. Culp and 12-month intervals, and surgery is per-
DeWeerd, Scardino and Prince) are useful formed only if a clear deterioration in renal
for those with a long-strictured segment of function is present.
the ureter. The proximal strictured ureter is
3.8 Treatment 93
Patients with Renal Differential Function <10 % Surgical Treatment for PUJ Obstruction
• Some recommend insertion of a neph- • Open pyeloplasty
rostomy tube to determine whether • Laparoscopic pyeloplasty
return of function will be sufficient. • Percutaneous endopyelotomy
• Others consider nephrectomy to relieve • Retrograde endopyelotomy
recurrent infection or renal • Endopyeloplasty
hypertension. • Robotic-assisted laparoscopic pyeloplasty
• In the absence of significant hydrone- • Percutaneous balloon dilatation
phrosis, some surgeons will observe • Endoscopic balloon dilatation
these patients and will consider nephrec-
tomy only if they develop hypertension
or recurrent urinary tract infection. – The success of laparoscopic pyeloplasty is
comparable with those of open pyeloplasty,
with success rates reported to be as high as
– In this technique, the obstructed segment is 96–98 %.
completely resected, the renal pelvis is – Laparoscopic pyeloplasty is reported to be
tapered with reanastomosis of the renal pelvis feasible and safe in children.
and ureter in a dependent funneled fashion. – Currently, laparoscopic pyeloplasty is per-
– The decision of whether to use a ureteral formed for older children.
stent transiently is still controversial. – It is technically unfeasible in very small
– Pyeloplasty can be performed through one children and infants because of space
of these approaches: constraints.
• A flank, dorsal lumbotomy – Laparoscopic pyeloplasty is a technically
• An anterior extraperitoneal approach demanding procedure that generally requires
• Laparoscopic pyeloplasty significant laparoscopic experience.
• Robotic assisted pyeloplasty – A small intrarenal pelvis is a relative con-
– The success rate of open Anderson-Hynes traindication to laparoscopic pyeloplasty.
dismembered pyeloplasty for treating PUJ – Laparoscopic pyeloplasty being a mini-
obstruction exceeds 95 %. mally invasive technique has several advan-
– There are those who use ureteral stents tages including:
routinely. • Shorter hospital stay
– Others prefer using a double “J” stent. • Faster recovery
– The use of perianastomotic drain following • Decreased morbidity
the repair is also controversial. • Better cosmetic result
– The routine use of nephrostomy is also • The success rates are comparable with
controversial. those of open pyeloplasty
– While open pyeloplasty is still considered – Laparoscopic pyeloplasty is divided
the standard treatment of UPJ obstruction according to the approach into two types:
in infants, laparoscopic pyeloplasty, with • Transperitoneal laparoscopic pyeloplasty
or without robotic assistance, is the treat- • Retroperitoneoscopic laparoscopic
ment of choice in older children and in pyeloplasty
most adults. – Laparoscopic pyeloplasty can be offered to
• Laparoscopic pyeloplasty: patients with:
– Traditionally, PUJ obstruction has been • Severe hydronephrosis
repaired with an open pyeloplasty. • Aberrant crossing vessels
– Laparoscopic pyeloplasty was first intro- • Long-segment PUJ strictures
duced in adults in 1993 by Schuessler. • Secondary PUJ obstruction
• PUJ obstruction and concomitant renal and difficult suturing.

calculi – One advantage of this technique is better
• Anomalous and solitary kidneys. cosmetic results.
• Failed open pyeloplasty • Endoscopic treatment of PUJ obstruction
– The success rates of transperitoneal laparo- (Endopyelotomy):
scopic pyeloplasty and retroperitoneo- – This is an endoscopic incision of the PUJ.
scopic laparoscopic pyeloplasty are – The aim is to create a more funneled
comparable (96.4 % versus 96.6 %). drainage system and to bring the PUJ
– A skill full laparoscopic surgeon is an more dependent or below the area of
important factor for this success rate. obstruction.
– Retroperitoneoscopic laparoscopic pyelo- – Endoscopic incision is performed through
plasty takes more operative time when the obstructing segment of the PUJ.
compared with transperitoneal laparo- – This is performed either as:
scopic pyeloplasty owing to the limits of • An antegrade (percutaneous)
working space and more difficult endopyelotomy
suturing. • A retrograde (endoscopic) endopyelot-
– Transperitoneal laparoscopic pyeloplasty omy via a ureteroscope
on the other hand is known to be associated – In a percutaneous endopyelotomy, a small
with: incision is made in the flank through which
• A significantly greater postoperative a scope is advanced through the kidney into
pain the renal pelvis to incise the UPJ.
• A higher requirements for analgesics – Ureteroscopic endopyelotomy involves
• A higher rate of temporary ileus passing a scope through the urethra, blad-
• A longer hospital stay der and ureter to incise the PUJ.
– It is now recommended that open pyelo- – The endopyelotomy incision is performed
plasty is the procedure of choice in infants through the area of obstruction with:
younger than 6 months. Laparoscopic pyelo- • A laser
plasty is reserved for older children and to be • An electrocautery
done by skillful laparoscopic surgeons. • An endoscopic scalpel
• Robotic-assisted laparoscopic pyeloplasty: – The vascular anatomy at the PUJ is impor-
– Robotic-assisted laparoscopic pyeloplasty tant during an endopyelotomy.
has become increasingly popular to treat – Most vessels associated with PUJ lie in the
PUJ obstruction. anteromedial plane but accessory vessels
– The da Vinci robotic surgical system has may lie posteriorly or laterally.
been used successfully to treat PUJ – If an endoscopic incision is made in the
obstruction. posterior-lateral plane, intraoperative hem-
– Suturing the anastomosis in the PUJ is orrhage may occur.
much easier when compared to the laparo- – The best recommendation is to make sure
scopic technique. that all incisions in the ureteral narrowing
– The results are similar to those of conven- are directed laterally to minimize the
tional laparoscopic pyeloplasty. chance for damage to the lower pole
– It is costly and collision of the robotic arms vessel.
in small infants is another drawback. – Prior to incising a PUJ obstruction, it is
• Single-port pyeloplasty: important to evaluate adjacent ureteral vas-
– In this technique, laparoscopic pyeloplasty culature using either an intraluminal ultra-
is performed via a single port placed at the sonography, CT-scan or MRA.
umbilicus. – Endopyelotomy is contraindicated in the
– This is technically challenging owing to presence of a crossing posterior or lateral
instrument crowding, loss of triangulation, vessel (Figs. 3.45 and 3.46).
3.8 Treatment 95
URETER ABERRANT
VESSEL
ABERRANT
VESSEL URETER
Figs. 3.45 and 3.46 Intraoperative photographs showing an aberrant vessel crossing and compressing the ureter lead-
ing to PUJ obstruction
– The endoscopic incision should be per- – The procedure is performed through a per-
formed full-thickness through the PUJ and cutaneous tract via a 26 F nephroscope.
into perirenal fat. – It consists of horizontal suturing of a stan-
– To ensure a proper adequate incision, dard vertical endopyelotomy incision.
extravasation of contrast should be seen on – Indications for endopyeloplasty include:
pyelography during the procedure. • A short-segment PUJ obstruction
– Most surgeons dilate the newly incised area • Absence of crossing renal polar vessels
with a balloon catheter to help ensure a • No prior surgery in the PUJ.
complete incision. – The results of endopyeloplasty are compa-
– This is followed by prolonged ureteral rable to those of endopyelotomy.
stenting, for a period of 4–8 weeks. The • Ureterocalicostomy:
stent help keeps the incised PUJ open and – A partial nephrectomy is performed and
maintains renal drainage. the ureter is anastomosed to a lower-pole
– Endopyelotomy is a reasonable option in renal calyx.
patients with mild-to-moderate hydrone- – This is usually reserved for patients follow-
phrosis and reasonably good renal function. ing a failed open pyeloplasty when no
– The area of stricture should be short extrarenal pelvis and significant hilar scar-
(<1.5 cm), and no crossing vessels should ring are present.
be defined on preoperative or intraopera- • Balloon dilatations of PUJ obstruction
tive imaging. (Figs. 3.47 and 3.48):
– Endopyelotomy is also particularly useful – Balloon dilatation of PUJ obstruction
following a failed open or laparoscopic was first done in 1982 by Kadir et al in
pyeloplasty. 1982.
– The success rates with the percutaneous – Balloon dilatation can be done antegrade,
and ureteroscopic endopyelotomy are retrograde or combined and the success
80–90 %. rate is variable.
• Endopyeloplasty: – Percutaneous or endoscopic balloon dilata-
– This was first reported in 2002 by Gill et al tion of PUJ is another alternative to treat
from the Cleveland clinic. PUJ obstruction in children.
Guide wire
insertion
Pelvis Puncture – U/S guided
Balloon over guidewire

J-J stent insertion Flow check Inflated
Fig. 3.47 Clinical and radiological pictures showing the steps of percutaneous balloon dilatation of PUJ obstruction. A
double J-stent is left in place for 6–8 weeks
Fig. 3.48 Radiological photographs showing abolishing the wasting at the PUJ which is an important prognostic sign
– This is performed by interventional – A double “J” stent is passed percutaneously

radiologist. and left in place to keep the dilated site patent.
– The site of obstruction is defined and the – Balloon dilatations are most appropriate
stricture is dilated with balloon dilators. in pediatric populations because they are
3.9 Post-operative Complications and Follow-Up 97
the least invasive approach and are asso- 3.9 Post-operative Complications
ciated with the lowest risk of and Follow-Up
hemorrhage.
– Balloon dilatation of PUJ obstruction in • Open surgical pyeloplasty is known to be
infants and children is technically feasible, associated with complications which include:
safe and viable alternative to open or lapa- – Urinary tract infection and pyelonephritis
roscopic pyeloplasty. – Anastomotic leakage and urinary
– Ante grade (percutaneous) balloon extravasation
dilatation: – Recurrent pelviureteric junction obstruction
• All dilatations are done under general – Stenosis and stricture at the anastomosis
anesthesia. site
• Under ultrasound guidance, a puncture • The treatment of postoperative urinary leakage:
is made in the renal pelvis, followed by – Some surgeons advocate placing a drain
insertion of a Teflon coated (0.014– adjacent to the anastomosis to provide
0.035) guide wires into the renal pelvis drainage in case of a leak.
and through the PUJ. – The drain can be removed 48–72 h postop-
• Balloon catheters (2, 3, or 4 mm in eratively if there is no leak.
diameter) are passed over the guide – Others advocate insertion of a trans-
wire and used to dilate the PUJ anastomotic stent to keep the anastomosis
obstruction. open and drain the renal pelvis.
• The flow through the PUJ is checked – Some surgeons place a double J stent which
after dilatation and a double J-sent is is removed after few weeks.
inserted. – Postoperative leak without a drain can be
• A cutting balloon is used to widen the treated by placing a perianastomotic drain
area of stenosis and it is important percutaneously under ultrasound
during the process of dilatation to guidance.
abolish the area of wasting which is – Other methods to control the leak include:
confirmed radiologically under • Placement of percutaneous nephrostomy
fluoroscopy. • Placement of a ureteral stent
– This is especially so in infants where sur- • Postoperative complications following endo-
gery is technically difficult and in experi- pyelotomy include:
enced hands its efficacy is comparable to – Significant intraoperative bleeding if the
open or laparoscopic pyeloplasty. endoscopic incision is made inadvertently
– Generally, balloon dilatation and stenting into a major polar vessel.
has a lower success rate than the open or – Those with significant bleeding can be
laparoscopic pyeloplasty but this increases treated with emergency angiography and
in experienced hands where the results embolization of the bleeding vessel.
Balloon dilatation however, has a low mor- – Postoperative urinary tract infection
bidity and no mortality, less cost, no scars – Recurrence of PUJ obstruction.
and a short hospital stay. • A follow-up ultrasound should be obtained
– Balloon dilatation is an attractive alterna- approximately 4–12 weeks postoperatively to
tive to open or laparoscopic pyeloplasty as monitor the outcome.
first-line treatment for PUJ obstruction. • Over time, nearly all patients (up to 95 %)
This is specially so in infants where open have radiographic improvement and resolu-
and laparoscopic pyeloplasties are known tion of their symptoms.
to be technically difficultbecome compa- • Renal ultrasound is the main investigation for
rable to those of open or laparoscopic postoperative follow-up of patients with PUJ
pyeloplasty. obstruction.
• The first renal ultrasound is performed routine radionuclide renography with 99mtechne-
tium diethylenetriaminepentaacetic acid. J Urol.
4–6 weeks postoperatively.
1988;140(4):780–3.
– If the follow-up ultrasound shows improve- 12. Islek A, Güven AG, Koyun M, et al. Probability of
ment where there is decrease in the severity urinary tract infection in infants with ureteropelvic
of hydronephrosis, the patient can then be junction obstruction: is antibacterial prophylaxis
really needed? Pediatr Nephrol. 2011;26:1837.
followed by repeat ultrasound initially
13. Josephson S. Antenatally detected pelvi-ureteric junc-
1 year postoperatively and then every tion obstruction: concerns about conservative man-
2–3 years. agement. BJU Int. 2000;85:973.
– If the follow-up ultrasound does not show 14. Kim HJ, Jung HJ, Lee HY, et al. Diagnostic value of
anteroposterior diameter of fetal renal pelvis during
improvement in the degree of hydrone-
second and third trimesters in predicting postnatal sur-
phrosis, diuretic renography is performed gery among Korean population: useful information for
to detect persistent obstruction, which may antenatal counseling. Urology. 2012;79(5):1132–7.
require an additional surgical procedure. 15. Koff SA. Postnatal management of antenatal hydro-
nephrosis using an observational approach. Urology.
2000;55:609.
16. Kojima Y, Sasaki S, Mizuno K, Tozawa K, Hayashi
Y, Kohri K. Laparoscopic dismembered pyeloplasty
Further Reading for ureteropelvic junction obstruction in children. Int
J Urol. 2009;16(5):472–6.
1. Baek M, Park K, Choi H. Long-term outcomes of 17. Liang CC, Cheng PJ, Lin CJ, et al. Outcome of prena-
dismembered pyeloplasty for midline-crossing giant tally diagnosed fetal hydronephrosis. J Reprod Med.
hydronephrosis caused by ureteropelvic junction 2002;47:27.
obstruction in children. Urology. 2010;76:1463. 18. McMann LP, Kirsch AJ, Scherz HC, et al. Magnetic
2. Blanc T, Muller C, Abdoul H, et al. Retroperitoneal resonance urography in the evaluation of prenatally
laparoscopic pyeloplasty in children: long-term out- diagnosed hydronephrosis and renal dysgenesis.
come and critical analysis of 10-year experience in a J Urol. 2006;176:1786.
teaching center. Eur Urol. 2013;63:565. 19. Mearini L, Rosi P, Zucchi A, et al. Color Doppler
3. Chertin B, Pollack A, Koulikov D, et al. Conservative ultrasonography in the diagnosis of vascular abnor-
treatment of ureteropelvic junction obstruction in malities associated with ureteropelvic junction
children with antenatal diagnosis of hydronephrosis: obstruction. J Endourol. 2003;17(9):745–50.
lessons learned after 16 years of follow-up. Eur Urol. 20. Monn MF, Bahler CD, Schneider EB, et al. Trends
2006;49:734. in robot-assisted laparoscopic pyeloplasty in pediatric
4. Dangle PP, Kearns J, Anderson B, Gundeti MS. patients. Urology. 2013;81:1336.
Outcomes of infants undergoing robot-assisted lapa- 21. Parente A, Angulo JM, Romero RM, et al.
roscopic pyeloplasty compared to open repair. J Urol. Management of ureteropelvic junction obstruction
2013;190:2221. with high-pressure balloon dilatation: long-term out-
5. de Waard D, Dik P, Lilien MR, et al. Hypertension is come in 50 children under 18 months of age. Urology.
an indication for surgery in children with ureteropel- 2013;82:1138.
vic junction obstruction. J Urol. 2008;179:1976. 22. Penn HA, Gatti JM, Hoestje SM, et al. Laparoscopic
6. Duong HP, Piepsz A, Collier F, et al. Predicting the versus open pyeloplasty in children: preliminary
clinical outcome of antenatally detected unilateral report of a prospective randomized trial. J Urol.
pelviureteric junction stenosis. Urology. 2013;82:691. 2010;184:690.
7. Fernbach SK, Maizels M, Conway JJ. Ultrasound 23. Piaggio LA, Franc-Guimond J, Noh PH, et al.
grading of hydronephrosis: introduction to the system Transperitoneal laparoscopic pyeloplasty for primary
used by the Society for Fetal Urology. Pediatr Radiol. repair of ureteropelvic junction obstruction in infants
1993;23(6):478–80. and children: comparison with open surgery. J Urol.
8. Gill IS, Desai MM, Kaouk JH, Wani K, Desai 2007;178:1579.
MR. Percutaneous endopyeloplasty: description of 24. Riachy E, Cost NG, Defoor WR, et al. Pediatric
new technique. J Urol. 2002;168(5):2097–102. standard and robot-assisted laparoscopic pyelo-
9. González R, Schimke CM. Ureteropelvic junction plasty: a comparative single institution study. J Urol.
obstruction in infants and children. Pediatr Clin N 2013;189:283.
Am. 2001;48:1505. 25. Roarke MC, Sandler CM. Provocative imag-
10. Heinlen JE, Manatt CS, Bright BC, et al. Operative ver- ing. Diuretic renography. Urol Clin N Am.
sus nonoperative management of ureteropelvic junc- 1998;25(2):227–49.
tion obstruction in children. Urology. 2009;73:521. 26. Romao RL, Koyle MA, Pippi Salle JL, et al. Failed
11. Heyman S, Duckett JW. The extraction factor: an pyeloplasty in children: revisiting the unknown.
estimate of single kidney function in children during Urology. 2013;82:1145.
Further Reading 99
27. Sampaio FJ, Favorito LA. Ureteropelvic junction ste- 33. Tan HL, Najmaldin A, Webb DR. Endopyelotomy for
nosis: vascular anatomical background for endopy- pelvi-ureteric junction obstruction in children. Eur
elotomy. J Urol. 1993;150(6):1787–91. Urol. 1993;24:84.
28. Seideman CA, Tan YK, Faddegon S, Park SK, Best SL, 34. Tasian GE, Casale P. The Robotic-Assisted
Cadeddu JA, et al. Robot-assisted laparoendoscopic Laparoscopic Pyeloplasty: Gateway to Advanced
single-site pyeloplasty: technique using the da Vinci Reconstruction. Urol Clin N Am. 2015;42(1):89–97.
Si robotic platform. J Endourol. 2012;26(8):971–4. 35. Turner 2nd RM, Fox JA, Tomaszewski JJ, et al.
29. Song SH, Lee SB, Park YS, Kim KS. Is antibiotic pro- Laparoscopic pyeloplasty for ureteropelvic junction
phylaxis necessary in infants with obstructive hydro- obstruction in infants. J Urol. 2013;189:1503.
nephrosis? J Urol. 2007;177(3):1098–101. 36. Ulman I, Jayanthi VR, Koff SA. The long-term fol-
30. Stein RJ, Berger AK, Brandina R, et al. lowup of newborns with severe unilateral hydro-
Laparoendoscopic single-site pyeloplasty: a compari- nephrosis initially treated nonoperatively. J Urol.
son with the standard laparoscopic technique. BJU 2000;164:1101.
Int. 2011;107(5):811–5. 37. Varda BK, Johnson EK, Clark C, et al. National
31. Sukumar S, Djahangirian O, Sood A, et al. Minimally trends of perioperative outcomes and costs for open,
invasive vs open pyeloplasty in children: the differ- laparoscopic and robotic pediatric pyeloplasty. J Urol.
ential effect of procedure volume on operative out- 2014;191:1090.
comes. Urology. 2014;84:180. 38. Yeung CK, Tam YH, Sihoe JD, et al.
32. Symons SJ, Bhirud PS, Jain V, Shetty AS, Desai Retroperitoneoscopic dismembered pyeloplasty for
MR. Laparoscopic pyeloplasty: our new gold stan- pelvi-ureteric junction obstruction in infants and chil-
dard. J Endourol. 2009;23(3):463–7. dren. BJU Int. 2001;87:509.
Renal Tumors in Children
4
4.1 Introduction • Currently, as a result of better understand-

ing of these tumors and the multimodal
• Renal tumors are rare in children, with some approach to therapy, survival of these
of them being highly treatable and usually patients has improved to its current rate of
curable. more than 80 %.
• The type of tumor found through pathological • The diagnosis of renal tumors of childhood is
examination is very predictive of the outcome based on:
of children with renal tumors. – Clinical presentation
• The determination of tumor type is very – Radiological evaluation
important so that the children can receive the – Histopathologic examination
appropriate therapy. • The clinical presentation and radiographic
• Renal tumors in children comprise a spectrum appearance of these tumors are not unique to
ranging from the benign neonatal congenital each tumor, and the diagnosis can only be
mesoblastic nephroma to the highly malignant confirmed by histological evaluation.
anaplastic Wilms’ tumor and Rhabdoid tumor • The histological diagnosis is also important
of the kidney. to decide the most appropriate adjuvant
• Many pediatric renal tumors were previously treatment of these tumors as these tumors
lumped together and categorized as Wilms range from chemosensitive Wilms’ tumors
tumor. to nonchemosensitive renal cell
• However, in recent years several specific carcinoma.
tumors have been recognized as distinct • As with most tumors, a staging system has
pathologic entities. been developed to categorize patients for the
• These are separate from the classic Wilms appropriate treatment.
tumor.
• Wilms tumor (nephroblastoma) is the com- • Patients with tumors confined to the kidney
monest renal tumor and accounts for 87 % of that can be removed completely have the best
pediatric renal tumors. survival rate.
• Although Wilms tumor is the most common • Patients who have unfavorable histology are
pediatric renal malignancy, it is often indistin- not very responsive to chemotherapy or radia-
guishable from other rare but more aggressive tion therapy and complete surgical excision is
tumors like rhabdoid tumor of the kidney and essential.
renal clear cell sarcoma or the more benign • There are several renal tumors in children and
tumors like mesoblastic nephroma. these include:

102 4 Renal Tumors in Children
– Neuroepithelial tumors of the kidney

Age at Presentation for Renal Malignancies – Lymphoma
1. Wilms tumor – Renal medullary carcinoma
• Unilateral Wilms tumor: 1–11 year – Desmoplastic small round cell tumor of the
(Mean 3.5 year) kidney
• Bilateral Wilms tumor: – Others (Fibroma, Leiomyoma,
2 months–2 year (Mean 15 months) Leiomyosarcoma, Primary renal synovial
2. Nephroblastomatosis: 6–18 months sarcoma, Anaplastic sarcoma of the kidney)
3. Renal cell carcinoma: 6 months–60 year
(Commonly 10–20 year)
4. Mesoblastic nephroma: 0–1 year 4.2 Wilms’ Tumor
(Commonly 1–3 months)
5. Multilocular cystic renal tumor 4.2.1 Introduction
• Cystic nephroma: Adult female
• Cystic partially differentiated • Wilms’ (/vɪlmz/) tumor, or nephroblastoma is
nephroblastoma: 3 months–4 year one of the commonest tumors of the kidneys
(Commonly 1–2 year) that typically occurs in children.
6. Clear cell sarcoma: 1–4 year (Mean • It is named after Dr. Max Wilms, the German
2 year) surgeon (1867–1918) who first described it.
7. Rhabdoid tumor: 6 months–9 year • Wilms’ tumor, or nephroblastoma is a malig-
(Commonly 6–12 months) nant tumor of the kidneys that typically occurs
8. Angiomyolipoma: 6–41 year (Mean in children (Fig. 4.1).
10 year) • It makes up 87 % of pediatric renal tumors.
9. Renal medullary carcinoma: • Wilms tumor is the fourth most common
10–39 year (Mean 20 year) childhood cancer.
10. Ossifying renal tumor of infancy: • It is also the most common abdominal malig-
6 days–14 months (Commonly nancy in children.
1–3 months) • Wilms’ tumor accounts for 6–7 % of all child-
11. Metanephric adenoma: 15 months– hood cancers.
83 year • In North America about 450–500 new cases of
12. Lymphoma Wilms tumor are diagnosed each year.
• Hodgkin lymphoma: >10 year
(Commonly late teens
• Non-Hodgkin lymphoma: Any age
(Commonly child <10 year) WILMS
TUMOR
– Wilms’ tumor
– Cystic partially differentiated
nephroblastoma
– Mesoblastic nephroma NORMAL
URETER KIDNEYY
– Renal cell carcinoma
– Clear cell sarcoma
– Rhabdoid tumor of the kidney
– Ossifying renal tumor of infancy Fig. 4.1 A clinical photograph showing Wilms tumor
– Angiomyolipoma arising from the upper part of the kidney
4.2 Wilms’ Tumor 103
• Wilms tumor is relatively more common in survival of these patients has improved mark-
blacks than in whites and is rare in East edly over the years.
Asians. • At present, with early diagnosis and current
• For unknown reasons, Wilms tumor is more multimodality therapy, approximately
common among children of African descent. 80–90 % of children with Wilms tumor
• Most cases of Wilms’ tumor occur among survive.
children between 3 and 3.5 years old. – This is attributed to The National Wilms’
• Girls are slightly more likely to develop Tumor Study Group (NWTSG) and the
Wilms’ tumor than are boys. International Society of Pediatric Oncology
• The majority (75 %) of Wilms’ tumor cases (SIOP) who have identified several chemo-
occur in otherwise normal children. therapeutic agents through their clinical trials.
• In about 25 % of cases, Wilms’ tumors are • Wilms tumor arises from persistent metaneph-
associated with other developmental ric blastemal.
abnormalities. • Pathologically, Wilms tumors are described as
• Most nephroblastomas are unilateral affecting being triphasic made up of three elements:
one kidney only. – Metanephric blastema
• This however is not the case in patients with – Stroma (mesenchyme)
Denys-Drash syndrome who mostly have – Epithelium
bilateral or multiple tumors. • Add to this the presence of abortive tubules
• The majority of nephroblastomas are unilat- and glomeruli surrounded by a spindled cell
eral and bilateral Wilms tumor are seen in stroma. The stroma may include striated mus-
5–10 % of cases. cle, cartilage, bone, fat tissue, and fibrous
• In 5–10 % of patients, both kidneys are tissue.
affected: • The mesenchymal component may include
– At the same time (synchronous bilateral cells showing rhabdomyoid differentiation or
Wilms tumor). malignancy (rhabdomyosarcomatous Wilms).
– Or one after the other (metachronous bilat- • Pathologically, Wilms tumors is divided into
eral Wilms tumor). two prognostic groups:
• Wilms’ tumor has a classic histologic picture – Favorable: The tumor contains well devel-
which is called triphasic composed of epithe- oped components.
lial, blastemal, and stromal elements. – Anaplastic: The tumor contains diffuse
• Approximately 80–90 % of Wilms’ tumors anaplasia (poorly developed cells).
have favorable histology. • It was shown that mutations of the WT1 gene
• About 3–7 % of Wilms’ tumors are character- on chromosome 11p13 are seen in approxi-
ized by anaplastic changes. If these changes mately 20 % of Wilms tumors.
are present diffusely throughout the tumor • At least half of the Wilms tumors with muta-
(diffuse anaplasia), they are predictive of a tions in WT1 also carry mutations in CTNNB1,
poor outcome. the gene encoding the proto-oncogene
• Wilms’ tumors are usually encapsulated and beta-catenin.
vascularized and in cases of metastasis it is • It was shown also that a gene on the X chro-
usually to the lungs. mosome, WTX, is inactivated in up to 30 % of
• Two renal tumor types (Clear cell sarcoma of Wilms tumor cases.
the kidney and Rhabdoid tumor of the kidney) • A tumor biopsy is not typically performed due
were previously included in the category with to the risk of creating fragments of cancer tis-
unfavorable Wilms’ tumors. Currently, these sue and seeding the abdomen with malignant
are considered separate malignant entities. cells.
• The overall prognosis of Wilms’ tumor fol- • Children with Beckwith-Wiedemann syn-
lowing surgical excision is excellent and the drome, WAGR syndrome and Denys-Drash
syndrome, have increased risk of Wilms followed by serial ultrasonography (US) every
tumor. 3 months up to 7 years of age because the risk
• There is a definite genetic predisposition to of developing Wilms tumor after the age of
Wilms’ Tumor in children with aniridia. This 7 years decreases significantly.
is due to deletions in the p13 band on chromo- • Wilms tumor occasionally arises in the extra-
some 11. renal retroperitoneum, presumably within
• The treatment of unilateral Wilms’ tumor is mesonephric remnants (Extra Renal Wilms
nephrectomy followed by chemotherapy, with Tumor).
or without postoperative radiotherapy. • The “teratoid Wilms tumor”:
Chemotherapy regimens typically comprise – This is a Wilms tumor characterized by tis-
vincristine and dactinomycin; doxorubicin sue differentiation within the tumor cells
and then cyclophosphamide and etoposide are such as bone, cartilage, and muscle.
added for increasingly high-risk disease. • The vast majority of Wilms tumors demon-
• Wilms tumor may spread to the lungs, liver, or strate favorable rather than unfavorable histo-
nearby lymph nodes. pathologic findings and anaplasia correlates
• Wilms tumor is known to be associated with directly with a negative prognosis and resis-
congenital anomalies: tance to chemotherapy. It is characterized by
– Cryptorchidism (2.8 %) atypical mitoses or hyperchromatic cells with
– Hemihypertrophy (2.5 %) large nuclei.
– Hypospadias (1.8 %)
– Sporadic aniridia
• Two loci on chromosome 11 have been impli- 4.2.2 Etiology
cated in the genesis of Wilms tumors.
– Locus 11p13 is known as the WT1gene • Wilms tumor is thought to be caused by altera-
– Locus 11p15 is known as the WT2 gene. tions of genes responsible for normal genito-
– An abnormal WT1 gene is present in urinary development.
patients with WAGR syndrome: • This is supported by the common congenital
• Wilms tumor urological anomalies associated with Wilms
• Aniridia tumor including:
• Genitourinary abnormalities – Cryptorchidism
• Mental retardation – A double collecting system
– An abnormal WT1 gene is present in – Horseshoe kidney
patients with Denys-Drash syndrome: – Hypospadias
• Male pseudohermaphroditism • WT1 gene and other genetic loci
• Progressive glomerulonephritis – WT1 encodes a transcription factor critical
– An abnormal WT2 gene is present in to normal renal and gonadal development.
patients with Beckwith-Wiedemann syn- – WT1, the first Wilms tumor suppressor
drome or hemihypertrophy. gene at chromosomal band 11p13, was
– The genetics of Wilms tumor appear to be identified in children with Wilms tumor
multifactorial, and abnormalities at other who also had aniridia, genitourinary anom-
sites, including chromosomes 1, 12, and 8, alies, and mental retardation (WAGR
are also recognized. syndrome).
– Familial Wilms tumor is rare, occurring in – Karyotypic analysis revealed constitutional
approximately 1 % of cases and is not asso- deletions within the short arm of 1 copy of
ciated with mutations in chromosome 11. chromosome 11.
• Screening for Wilms tumor in patients with – The 11p13 locus was subsequently demon-
associated syndromes should begin at 6 months strated to encompass numerous contiguous
of age with initial computed tomography (CT) genes, including the aniridia gene PAX6
and the Wilms tumor suppressor gene – Is usually a large, solitary and encapsulated
WT1. tumor.
– A second gene that predisposes individuals – It compresses the remaining normal kidney
to develop Wilms tumor has been identified parenchyma.
at chromosomal band 11p15. – On cut section, Wilms’ tumor is soft, homog-
– This locus was proposed on the basis of stud- enous and Tan-gray in color and may con-
ies in patients with both Wilms tumor and tain areas of hemorrhage and necrosis.
Beckwith-Wiedemann syndrome (BWS). • Histologically, Wilms’ tumor is a malignant
– Loci at 16q, 1p, 7p, and 17p have also been tumor composed of three elements (a triphasic
implicated in the biology of Wilms tumor, nephroblastoma) (Figs. 4.8, 4.9, 4.10, 4.11,
although these loci do not seem to predis- and 4.12):
pose individuals to develop a Wilms tumor. – Metanephric blastema
• Beckwith-Wiedemann syndrome (BWS): – Mesenchymal stroma
– This is an overgrowth syndrome character- – Epithelium
ized by visceromegaly, macroglossia, and • One of the characteristic histological features
hyperinsulinemic hypoglycemia. of Wilms’ tumor is the presence of abortive
– Patients with BWS are predisposed to have tubules and glomeruli surrounded by a spin-
several embryonal neoplasms, including dled cell stroma.
Wilms tumor. • The stroma may include striated muscles, car-
– Several loci for Wilms tumor and BWS tilage, bone, fat tissue, and fibrous tissue.
have been proposed. These loci include: • Rhabdomyosarcomatous Wilms:
• The insulinlike growth factor II gene – The mesenchymal stroma may also include
(IGFII) cells showing rhabdomyoid differentiation.
• H19 The rhabdomyoid component may itself show
• p57kip2 features of malignancy. When this feature is
present, it is called rhabdomyosarcomatous
Wilms’ tumor. This particular sub-type shows
4.2.3 Histopathology poor response to chemotherapy.
• Wilms’ tumors may be separated into two
• Wilms tumor arise as a solid intrarenal mass prognostic groups based on pathologic
with a pseudocapsule. characteristics:
• The tumor may also arise from one pole of the – Favorable: This contains well developed
kidney. components.
• The tumor compresses the normal renal paren- – Anaplastic (unfavorable): This contains
chyma and leads to distortion of the collecting anaplastic cells which could be focal or dif-
system. fuse. This is associated with higher
• Wilms tumor typically spreads by direct frequencies of relapse and death especially
extension causing displacement but no encase- those with diffuse anaplasia.
ment of tissues. • The anaplasia in Wilms’ tumor is classified
• There may be vascular invasion of the renal into two types depending on the extent:
vein and inferior vena cava with occasional – Diffuse anaplasia
extension into the right atrium. – Localized anaplasia
• Metastases are most commonly found in the • Approximately 90 % of all Wilms tumors have
lungs (85 % of cases), liver, and regional favorable histology.
lymph nodes, and metastatic disease may also • About 3–7 % of Wilms tumors are character-
produce vascular invasion. ized by anaplastic changes.
• Pathologically, Wilms’ tumor (Figs. 4.2, 4.3, • The presence of diffuse anaplasia throughout
4.4, 4.5, 4.6, and 4.7): the tumor is a predictive of poor outcome.
Figs. 4.2, 4.3, and 4.4 Clinical photographs showing Wilms tumor. Note the compressed renal tissue at the periphery
• Clear cell sarcoma of the kidney and rhabdoid approximately one third of kidneys affected
tumor of the kidney were included in the unfa- by Wilms tumors.
vorable histology in the past and currently these • It was also shown that children younger than
are considered as separate malignant tumors. age 12 months diagnosed with perilobar neph-
• The presence of nephrogenic rests, and dys- rogenic rests have a markedly increased risk
plastic lesions of metanephric origin, are now of developing a contralateral Wilms tumor.
believed to represent precursor lesions of • The National Wilms Tumor Study (NWTS) and
Wilms tumor. These lesions are observed in Societe Internationale D’Oncologie Pediatrique
Fig. 4.5 A clinical photograph showing an excised Wilms

tumor. Note the fleshy, homogenous and Tan-gray in color
tumor
Fig. 4.7 A clinical photograph showing an excised Wilms

tumor. Note the areas of hemorrhage within the tumor
Fig. 4.8 A histological photograph of Wilms’ tumor

showing blastema ( ) tubules ( ) and spindle cells
Fig. 4.6 A photograph of a resected Wilms’ tumor. Note ( )
the gross appearance of Wilms’ tumor with the normal
part of the kidney being compressed by the tumor
– It has been found to make a protein that is

(SIOP) have made large contributions to the found mostly in the fetal kidney and in tis-
modern multimodal treatment, which consists sues that give rise to the genitourinary
of surgical excision, radiotherapy, and chemo- system.
therapy (adjuvant and/or neoadjuvant). These – Inactivation of this gene may be responsi-
oncologic treatments achieve a remarkable ble for the occurrence of Wilms tumor.
long-term overall survival rate of 90 %. – Mutations of the WT1 gene on chromo-
• Most cases of Wilms tumor do not have muta- some 11 p 13 are observed in approxi-
tions in any of the genes. mately 20 % of Wilms’ tumors.
• A gene on the X chromosome, WTX, is inac- – At least half of the Wilms’ tumors with
tivated in up to 30 % of Wilms’ tumor cases. mutations in WT1 also carry mutations in
• The gene WT1: CTNNB1, the gene encoding the proto-
– This is also called Wilms tumor suppressor oncogene beta-catenin.
gene.
Figs. 4.9 and 4.10 Histological picture of Wilms’ tumor showing tubules and spindle cells
Figs. 4.11 and 4.12 Histological pictures showing anaplastic Wilms’ tumor. Note the large cells with large nuclei
4.2.4 Nephroblastomatosis microscopic foci called nephrogenic rests

(renal blastema).
• The fetal kidney is formed by the development • Renal blastema and nephroblastomatosis are
of nephrons from fetal metanephric blastema interrelated conditions closely related to
surrounding the ureteric bud. Wilms tumors (Figs. 4.13 and 4.14).
• The fetal renal tissue matures into normal • The persistence of primitive renal blastema
renal parenchyma during gestation, but, occa- beyond 4 months of age is abnormal except in
sionally, fetal tissue persists into infancy as small microscopic rests.
Figs. 4.13 and 4.14 Abdominal CT-scan showing bilateral nephroblastomatosis and Wilms’ tumor
• Nephroblastomatosis is defined as the pres- with well demarcated low power

ence of multifocal nephrogenic rests. margins.
• Nephrogenic rests are foci of metanephric • They are associated with Beck-with-
blastema that persist beyond 36 weeks gesta- Wiedemann syndrome and hemihyper-
tion and have the potential for malignant trophy, Perlman syndrome
transformation into Wilms’ tumor. (visceromegaly, gigantism, cryptorchi-
• Nephrogenic rest are found incidentally in 1 % dism, polyhydramnios, characteristic
of infants. facies), and trisomy 18.
• It is currently believed that nephrogenic rests • Malignant degeneration into Wilms
give rise to approximately 30–40 % of Wilms’ tumor is most common in patients with
tumors. Beckwith-Wiedemann syndrome and
• Nephrogenic rests are found in up to 99 % of hemi-hypertrophy, occurring in 3 % of
bilateral Wilms’ tumors. cases.
• Nephrogenic rests are classified histologically – Intralobar rests:
as: • These are considerably less common
– Dormant, sclerosing, hyperplastic, or than the perilobar nephrogenic rest.
neoplastic. • They present anywhere within the kid-
– Dormant and sclerosing rests are usually ney and often have a more irregular and
microscopic and are not considered to have intermixed margins.
malignant potential. • They have a higher association with
– Hyperplastic and neoplastic rests are Wilms tumor development.
grossly visible as small tan nodules sur- • These rests are found in 78 % of patients
rounded by normal parenchyma. with Denys-Drash syndrome and nearly
• There are two pathologic subtypes of nephro- 100 % of patients with sporadic aniridia
genic rest based on location (perilobar and and are also seen in patients with WAGR
intralobar): syndrome.
– Perilobar rest (90 %) – Ultrasonographic detection of these rests is
– Intralobar rest (10 %). This is more associ- possible, but sonography lacks the sensitiv-
ated with Wilms’ tumor. ity of CT and MRI.
– Prilobar rests: – On CT, macroscopic nephrogenic rests
• They are found in subcapsular location appear as low-attenuation peripheral nodules
with poor enhancement relative to that of • Abdominal pain (25 %)

adjacent normal renal parenchyma. • Wilms’ tumor can present with (Figs. 4.15,
– On MRI, the nodules demonstrate low- 4.16, 4.17, and 4.18):
signal-intensity foci on both T1-weighted – Abdominal swelling or distension
and T2-weighted images. – Abdominal mass
– On sonograms, the affected kidney may be – Abdominal pain
enlarged and lobulated with multiple – Fever
hypoechoic areas. Corticomedullary differ- – Nausea and vomiting
entiation may be lost. – Hematuria
– After such findings are discovered, three – Hypertension
monthly ultrasound examinations should – Urinary tract infection
be performed to detect their progression to – Wilms’ tumor can grow rapidly as a result
a Wilms’ tumor. of bleeding into the tumor or from actual
– Lymphoma can mimic the appearance of tumor growth.
nephroblastomatosis but is unusual in – Bleeding into the tumor will lead to anemia
infants and young children. and if severe will result in heart failure.
• Treatment for nephrogenic rests: • Hematuria:
– This is controversial. – May be seen in 10–15 % of cases.
– Some investigators recommend chemo- – This can be microscopic or gross
therapy, whereas others maintain that close hematuria.
serial radiologic evaluation of enlarging – This is seen often after a relatively minor
masses is sufficient. trauma and injury of the enlarged kidney
– Screening for Wilms tumor in patients with by the tumor.
syndromes associated with nephrogenic – Hematuria may be seen as a late presenta-
rests should be performed. tion that is usually associated with tumor
– Ultrasound is a good follow-up investigation, invasion of the calyces and considered a
cheap, readily available and can be done eas- bad prognostic sign.
ily without anesthesia, however CT-scan is • Hypertension:
the method of choice for follow-up. – As many as one third of patients with
– On imaging, nephroblastomatosis appear Wilms tumor present with hypertension.
as discrete, homogeneous, non-enhancing Their blood pressure usually normalizes
renal masses. after nephrectomy, but they occasionally
– Any rapid growth, inhomogeneity, or het- require prolonged therapeutic intervention
erogeneous enhancement should be taken – Increased blood pressure may be present in
seriously and worrisome for development 20 % of Wilms’ tumor cases.
of Wilms. – Hypertension in Wilms’s tumor results
from pressure effect of the tumor on the
renal vessels leading to increased secretion
4.2.5 Clinical Features of rennin.
• Rarely, the tumor may produce erythropoietin
• The usual presentation of Wims’ tumor is with a leading to increased red blood cells produc-
painless abdominal mass discovered accidently tion and polycythemia.
by the parents or by a physician during a routine • Patients with Wilms tumor can present with
physical examination. It is not uncommon for hemorrhage into their tumor leading to hypo-
the mother to discover the mass while giving tension, anemia, and fever.
bath to her child. This is the presentation in • Rarely patients with Wilms tumor and lung metas-
more than 80 % of children with Wilms tumor. tases may present with respiratory symptoms.
• The mass is discovered after coincidental • Wilms’ tumor can occur as part of rare genetic
trauma in up to 10 % of cases. syndromes, including:
Figs. 4.15 and 4.16 Clinical photographs showing children with left and right Wilms tumors
Fig. 4.18 A clinical photograph showing a very large

Wilms tumor. This proved by abdominal CT-scan to be
secondary to hemorrhage inside the tumor
Fig. 4.17 A clinical photograph showing a very large

Wilms tumor filling almost the whole abdomen
– WAGR syndrome. This syndrome includes: – A double collecting system

• Wilms tumor. – Horseshoe kidney
• Aniridia. • Wilms’ tumor can occur as part of rare syn-
• Abnormalities of the genitals and uri- dromes, including:
nary system. – WAGR syndrome: This syndrome includes
• Mental retardation. Wilms’ tumor, aniridia, abnormalities of
– Denys-Drash syndrome. This syndrome the genitals and urinary system, and mental
includes: retardation.
• Wilms’ tumor. – Denys-Drash syndrome: This syndrome
• Kidney disease. includes Wilms’ tumor, kidney disease and
• Male pseudohermaphroditism. male pseudohermaphroditism.
• These patients mostly have bilateral or – Beckwith-Wiedemann syndrome (BWS):
multiple tumors. • BWS is an overgrowth syndrome char-
– Beckwith-Wiedemann syndrome. This acterized by visceromegaly, macroglos-
syndrome includes: sia, omphalocele and hyperinsulinemic
• Omphalocele. hypoglycemia.
• A large tongue (macroglossia). • Patients with BWS are predisposed to
• Enlarged internal organs have several embryonal neoplasms,
(visceromegaly). including Wilms’ tumor.
• Hypoglycemia. • Few candidate loci for Wilms’ tumor
and BWS have been proposed. These
loci include the insulinlike growth fac-
4.2.6 Risk Factors for Wilms’ Tumor tor II gene (IGFII), H19 (for an untrans-
lated ribonucleic acid [RNA]), and that
• Female gender encoding for p57kip2.
– Girls are slightly more likely to develop • WT1 gene:
Wilms’ tumor than are boys. – WT1, the first Wilms’ tumor suppressor
• Black children have a slightly higher risk of gene at chromosomal band 11p13, was
developing Wilms’ tumor than do children of identified as a direct result of the study of
other races. children with Wilms’ tumor who also had
– People of African descent have the highest aniridia, genitourinary anomalies, and
rates of Wilms’ tumor. mental retardation (WAGR syndrome).
• Children of Asian descent appear to have a – WT1 encodes a transcription factor critical
lower risk of developing Wilms’ tumor than to normal renal and gonadal development.
do children of other races. – The WT1 gene is the specific target of muta-
• A family history of Wilms’ tumor increases tions and deletions in a subset of patients
the risk of developing Wilms’ tumor. with sporadic Wilms’ tumors, as well as in
• Wilms’ tumor occurs more frequently in chil- the germline of some children (e.g., those
dren with certain congenital abnormalities, with Denys-Drash syndrome) with a genetic
including: predisposition to develop this cancer.
– Aniridia (partial or total absence of the iris) • Additional genetic loci:
• A genetic predisposition to Wilms’ – A second gene that predisposes individuals
Tumor in individuals with aniridia has to develop the Wilms’ tumor has been iden-
been established, due to deletions in the tified (but has not yet been cloned) telo-
p13 band on chromosome 11. meric of WT1, at 11p15. This locus was
– Hemihypertrophy proposed on the basis of studies in patients
– Undescended testicles with both Wilms’ tumor and Beckwith-
– Hypospadias Wiedemann syndrome (BWS), another
congenital Wilms’ tumor predisposition • Stage II (23 % of patients)

syndrome linked to chromosomal band – Tumor extends beyond the kidney but is
11p15. completely excised.
– Loci at 16q, 1p, 7p, and 17p have also been – No residual tumor apparent at or beyond
implicated in the biology of Wilms tumor, the margins of excision.
although these loci do not seem to predis- – Any of the following conditions may also
pose individuals to develop a Wilms’ tumor. exist:
Instead, they seem to be associated with the • Tumor involvement of the blood vessels
phenotype or the outcome. of the renal sinus and/or outside the
• Wilms tumor may be part of a genetic syn- renal parenchyma.
drome and certain birth defects can also increase • The tumor has been biopsied prior to
a child’s risk for developing Wilms tumor. removal or there is local spillage of
• The following genetic syndromes and birth tumor during surgery, confined to the
defects have been linked to Wilms tumor: flank.
– WAGR syndrome (Wilms tumor, aniridia, • Extensive tumor involvement of renal
abnormal genitourinary system, and mental sinus soft tissue.
retardation) • Stage III (20 % of patients)
– Beckwith-Wiedemann syndrome (viscero- – Inoperable primary tumor.
megaly, macroglossia, and hyperinsulin- – Lymph node metastasis.
emic hypoglycemia) – Tumor is present at surgical margins.
– Hemihypertrophy – Tumor spillage involving peritoneal sur-
– Denys-Drash syndrome faces either before or during surgery, or
– Cryptorchidism transected tumor thrombus.
– Hypospadias • Stage IV (10 % of patients)
• It is recommended that children with these – Stage IV Wilms tumor is defined as the
genetic syndromes and birth defects should be presence of hematogenous metastases
screened for Wilms tumor every 3 months (lung, liver, bone, or brain), or lymph node
until age 8 years. metastases outside the abdomenopelvic
region (Fig. 4.19).
• Stage V (5 % of patients)
4.2.7 Staging of Wilms Tumor – Stage V Wilms tumor is defined as bilateral
renal involvement at the time of initial
• Staging of Wilms tumor is based on anatomi- diagnosis (Figs. 4.20 and 4.21).
cal findings and tumor cells pathology. – In term of treatment and prognosis, for patients
• The Children’s Oncology Group staging of with bilateral Wilms tumor, it is important to
Wilms tumors: stage each side separately according to the
• Stage I (43 % of patients) above criteria on the basis of extent of disease
– Tumor is limited to the kidney and is com- and plan treatment according to the side with
pletely excised. the more advanced stage.
– The surface of the renal capsule is intact. • The National Wilms Tumor Study Group
– The tumor is not ruptured or biopsied (open (NWTSG) and the International Society of
or needle) prior to removal. Pediatric Oncology (SIOP) have contributed
– No involvement of extrarenal or renal sinus to the overall improved survival of children
lymph-vascular spaces with Wilms tumors. They improved our under-
– No residual tumor apparent beyond the standing of the molecular mechanisms that
margins of excision. contribute to the development of Wilms tumor
– Metastasis of tumor to lymph nodes not and identified several chemotherapeutic
identified. agents through clinical trials.
• Children with bilateral Wilms tumor are treated • The aim of the specific investigations is to
with preoperative chemotherapy. This is impor- evaluate the:
tant because each kidney is staged separately, and – Site
preoperative chemotherapy may lead to com- – Size
plete resolution of disease in one kidney or reduc- – Extent of the tumor
tion in the size of both tumors. This will make it – Presence or absence of secondaries
possible to subsequently do nephrectomy on one – Presence or absence of synchronous Wilms
side only or bilateral partial nephrectomies. tumors
– It is also important to make sure that there
is a normally functioning contralateral
4.2.8 Investigations kidney
• There are general and specific investigations.
• It is important to investigate children with • The general investigations include:
Wilms tumor. – A complete blood count
– Electrolytes
– Liver function tests
– BUN and creatinine
– Urinalysis
– Coagulation studies
– Serum calcium
• It is of great importance to exclude extension
of the tumor into the renal vein as well as the
inferior vena cava.
• A plain abdominal radiograph (KUB)
(Figs. 4.22 and 4.23):
– This often shows a soft tissue density with dis-
placement of bowel loops inferiorly and to the
contralateral side.
Fig. 4.19 CT-scan of the chest showing secondaries from
– Occasionally calcification (<10 %) is seen.
Wilms tumor
Figs. 4.20 and 4.21 Abdominal CT-scan in two patients with bilateral Wilms’ tumor. The sizes of both tumors is
different
Figs. 4.22 and 4.23 Abdominal radiograph showing a soft tissue density in two patients with right and left Wilms
tumor. Note the mass compressing and pushing the bowel downward and to the other side
– The calcification usually is located on the – Doppler ultrasound is a valuable investiga-

edge of the tumor whereas calcification in tion in detecting tumor extension in the
neuroblastoma is speckled throughout. renal vein and inferior vena cava and the
• Chest radiograph (Figs. 4.24, 4.25, and 4.26): extent of extension.
– This is to confirm or exclude the presence – This shows a solid intrarenal mass.
of secondaries in the lungs. – The mass has heterogeneous echogenicity,
– Distant metastasis in Wilms’ tumor is com- which represents hemorrhage, fat, necrosis,
monly seen in the lungs. or calcification.
– CT-scan of the chest is more informative • Abdominal and thoracic CT-scan (Figs. 4.31,
for the presence or absence of secondaries. 4.32, 4.33, 4.34, and 4.35):
– In children with Wilms’ tumor. CT-scan of – This defines the tumor site; identifies the
the chest and abdomen should be done presence of enlarged lymph nodes; evalu-
simultaneously. ates the contralateral kidney for possible
– Abnormalities seen on chest CT-scan how- presence of a second Wilms’ tumor;
ever, needs to biopsied to confirm the assesses extension of the tumor into the
diagnosis. renal veins, inferior vena cava and
• Abdominal ultrasound (Figs. 4.27, 4.28, 4.29, right atrium, and determines if the patient
and 4.30): has intra-abdominal secondaries to the
– This is valuable in determining the origin liver.
of the tumor, whether the mass is cystic or – It is also valuable in detecting nodal metas-
solid; and indicates if the tumor extends tases as well hemorrhage and areas of
into the renal veins and inferior vena cava. calcification within the tumor.
– It is also useful in evaluating the contralat- – It is important to visualize the contralateral
eral kidney and whether a synchronous kidney and document that it is functioning
tumor is present or not. using contrast.
Figs. 4.24, 4.25, and 4.26 Chest x-rays showing pulmonary secondaries from Wilms’ tumor
Figs. 4.27, 4.28, 4.29, and 4.30 Abdominal ultrasound showing left renal Wilms tumor in the upper one and bilateral
Wilms tumor in the lower two pictures
Figs. 4.31 and

4.32 Abdominal CT-scan
showing a very large left
Wilms tumor
– Thoracic CT-scan is important to detect imaging modality for determination of

pulmonary metastasis. Sometimes pulmo- caval patency and may be important in
nary metastasis are not seen on chest x-ray determining whether the inferior vena cava
and appear only on CT-scan. is directly invaded by the tumor or not.
• Intravenous urography (Figs. 4.36, and 4.37): – Wilms’ tumor demonstrates low signal
– In the past, this was one of the radiological intensity on T1-weighted images and high
investigation used to evaluate children with signal intensity on T2-weighted images.
Wilms’ tumor. • Tumor extension into the renal vein and IVC is
– This is also useful to show that a normal seen in 5–10 % of patients with Wilms tumor.
functioning contralateral kidney is present. • A cystic variant of Wilms tumor may mimic
– Currently, this is replaced by CT-scan and benign multilocular cystic nephroma.
MRI. • Small abnormalities seen on chest x-ray are
• MRI scanning (Figs. 4.38, 4.39, 4.40, 4.41, suggestive of secondaries but those seen on
4.42, and 4.43): CT-scan may need to be confirmed by biopsy.
– Abdominal magnetic resonance imaging • With the current radiological investigations,
(MRI) is reportedly the most sensitive physical inspection of the opposite kidney by
opening Gerota’s fascia as suggested previ-
ously to check for synchronous tumor is no
longer necessary.
• Abdominal and chest CT-scan is useful in
determining (Figs. 4.44, 4.45, 4.46, 4.47, 4.48,
4.49, 4.50, and 4.51):
– The origin of the tumor
– Involvement of the regional lymph nodes
and local recurrence
– Bilateral renal involvement
– To visualize the contralateral kidney and doc-
ument that it is functioning using contrast.
– Invasion into the renal vein and inferior
vena cava
Fig. 4.33 Abdominal CT-scan showing a very large right – Liver metastases
Wilms tumor
– Lung metastases
Figs. 4.34 and 4.35 Abdominal CT-scans showing bilateral Wilms tumor
Figs. 4.36 and 4.37 Intravenous urography showing left and right Wilms tumors. Note the normal functioning contra-
lateral kidney. Note also the distortion of the calcyeal system of the affected kidney
Figs. 4.38 and 4.39 Abdominal MRI showing left Wilms tumor. Note the normally functioning right kidney
• Diagnostic biopsy of lesions noted on the causing preoperative tumor spill, requiring
chest CT scan is recommended to confirm the whole abdominal radiotherapy.
diagnosis. – The National Wilms Tumor Study Group
• Histopathologic confirmation of Wilms tumor (NWTSG):
is essential. • Patients with unilateral Wilms tumor
• Transcutaneous biopsy is not usually recom- undergo nephrectomy immediately.
mended as this may complicate treatment by
Figs. 4.40 and 4.41 Abdominal MRI showing a large left side Wilms’ tumor with areas of hemorrhage and or necrosis.
Note also an associated congenital pancreatic cyst
Figs. 4.42 and 4.43 Abdominal MRI showing a large right side Wilms’ tumor
• During the procedure, the contralateral – The International Society of Pediatric

kidney is explored to ensure that the dis- Oncology (SIOP)
ease is indeed unilateral. • The diagnosis of Wilms tumor is pre-
• Lymph node biopsy samples are sumptive based on imaging findings
obtained for staging purposes. Lymph alone.
node dissection is not indicated. • Administration of chemotherapy
• Nephrectomy
4.2.9 Prognosis and Complications

of Wilms Tumor
• The prognosis is highly dependent on individ-

ual staging, histology and treatment.
• The overall 5-year survival is estimated to be
approximately 80–90 %.
• Tumor-specific loss-of-heterozygosity (LOH)
for chromosomes 1p and 16q identifies a sub-
set of Wilms tumor patients who have a sig-
Fig. 4.44 CT-scan of the chest showing pulmonary nificantly increased risk of relapse and death.
metastasis from Wilms tumor Children with loss of heterozygosity at 1p and
16q are treated with more aggressive
chemotherapy.
• Approximately 80–90 % of children with a
diagnosis of Wilms tumor survive with current
multimodality therapy.
• Patients who have tumors with favorable his-
tology have an overall survival rate of at least
80 % at 4 years after the initial diagnosis, even
in patients with stage IV disease.
• The 4-year relapse-free and overall survival
rates in patients with favorable-histology
Wilms tumor are as follows
Fig. 4.45 CT-scan of the chest showing liver metastasis

from Wilms tumor
Figs. 4.46 and 4.47 CT-scans of the abdomen showing local recurrence following resection of Wilms tumor
Survival rates in patients with favorable-histology

Wilms tumor
Stage Relapse-free survival % Overall survival, %
I 92 98
II 85 96
III 90 95
IV 80 90
Fig. 4.50 Abdominal CT-scan showing a large left

Wilms’ tumor. Note the areas of hemorrhage or necrosis in
the center
Fig. 4.48 Abdominal CT-scan showing bilateral Wilms’

tumor
Fig. 4.51 Aspiration cytology showing cells of Wilms’

tumor
• Children with a loss of heterozygosity at 1p

and 16q have a worse prognosis than do chil-
dren without this heterozygosity loss.
• The prognosis for patients who have a relapse
is not as good as it is for those with a newly
diagnosed Wilms tumor, with 40–80 % of
relapse patients expected to survive after sal-
Fig. 4.49 Abdominal CT-scan showing left side Wilms’ vage therapy.
tumor. Note the patent IVC and the presence of an
enlarged lymph node • Chemotherapy and radiation therapy can
induce second malignant neoplasms.
• Renal complications:
• Patients with synchronous bilateral tumors – Children with unilateral Wilms tumor who
have a 70–80 % survival rate, whereas those undergoes nephrectomy have a minimal risk
with metachronous tumors have a 45–50 % for impaired contralateral renal function.
survival rate. – There is usually a compensatory postnephrec-
• Patients with anaplastic Wilms tumor have a tomy hypertrophy of the remaining kidney.
worse prognosis compared with favorable his- – The function of the remaining kidney may
tology Wilms tumor; the 4-year overall sur- be affected in those who receive postopera-
vival rates are 83 %, 83 %, 65 % and 33 % for tive radiotherapy (Radiation-induced renal
stages I, II, III, and IV, respectively. damage).
– Renal function can be impaired in those – There is an increased risk for second malig-
with bilateral Wilms tumor. nant neoplasm following chemotherapy
– The risk factors for renal damage include: and or radiotherapy.
• Stromal predominant histology • Most secondary malignant neoplasms
• Intralobar rests reported (e.g., bone tumors, breast and
• Age at diagnosis of younger than thyroid cancers) have occurred in irradi-
24 months ated areas.
• Metachronous bilateral Wilms tumor • Certain chemotherapeutic agents, includ-
• WT1 mutation etiology. ing doxorubicin, dactinomycin, and vin-
• Hepatic complications: cristine, may contribute to an increased
– Hepatic damage in patients with Wilms risk for secondary malignancies.
tumor can be caused by radiation therapy • A recent interesting finding was that
and the use of cytotoxic drugs particularly female survivors of Wilms tumor have a
dactinomycin and vincristine. 9.1-fold increased risk of developing
– The dactinomycin hepatotoxicity is invasive breast cancer and had an esti-
dose-related. mated cumulative risk of invasive breast
– Radiotherapy is the main cause of hepatic cancer at age 40 of 4.5 %. The risk was
toxicity but this rare nowadays. highest among children who had been
– Hepatic toxicity was reported in 2.8–14.3 % treated with chest radiotherapy.
of children who did not receive radiotherapy.
– Some patients with Wilms tumor have
developed hepatic veno-occlusive disease. 4.2.10 Surgical Considerations
• Hepatic veno-occlusive disease is char-
acterized by hepatomegaly or pain in the • According to Children’s Oncology Group
right upper quadrant, jaundice, ascites, (COG), the treatment of Wilms tumor is
and unexplained weight gain. nephrectomy followed by chemotherapy, with
• It is seen in children with Wilms tumor or without postoperative radiotherapy.
undergoing nephrectomy first and in • Certain children with stage I disease and
those receiving combination chemo- favorable histology do well with nephrectomy
therapy before surgery. alone.
• Other complications include: • Radiotherapy:
– Congestive heart failure is a well-known – Postoperative radiotherapy is started within
complication of the administration of 14 days of nephrectomy.
anthracyclines (e.g. doxorubicin). – The current dose for radiation therapy for
– Radiation-induced pulmonary complica- favorable histology Wilms tumor is approx-
tions. This is more commonly seen in those imately 1,080 cGy for the abdomen and
who receive bilateral pulmonary irradiation. 1,200 cGy for the lung.
– Women who received whole-abdomen irra- – Patients with stage IV favorable histology
diation in childhood can develop ovarian Wilms tumor and lung metastases whose
failure. pulmonary lesions do not disappear after
– Male patients are at risk for testicular fail- 6 weeks of chemotherapy receive whole-
ure after whole-abdomen radiation therapy lung radiation therapy.
or certain types of chemotherapy, most • In North America:
notably that involving alkylating agents. – Patients with suspected Wilms’ tumor
– Radiation therapy may affect the growth of undergo nephrectomy immediately.
any given bone but the spine is most nota- – During this procedure, the contralateral
bly affected. The effect is dose related and kidney is explored to ensure that Wilms’
can lead to scoliosis. tumor is unilateral.
– Currently, may surgeons will not explore • The National Wilms’ Tumor Study Group
the contralateral kidney and will depend on (NWTSG) and the International Society of
preoperative CT-scan or MRI evaluation. Pediatric Oncology (SIOP) have identified
– Lymph node biopsy samples are obtained several chemotherapeutic agents through their
for staging purposes. clinical trials.
– Immediate nephrectomy is not performed in • At present, survival rates of children with
patients with bilateral Wilms’ tumor or those Wilms’ tumor are approximately 80–90 %.
with very large unresectable Wilms tumor. • Chemotherapy without initial surgical resec-
• In most European centers: tion can be used in the following situations:
– A presumptive diagnosis of Wilms’ tumor – Inoperable tumors (Figs. 4.52, 4.53, 4.54,
is made based on imaging findings alone. 4.55, 4.56, and 4.57):
– Administer chemotherapy before • Large tumors that involve vital structures
nephrectomy. make resection difficult; the complication rate
• Transcutaneous biopsy is not usually recom- is high, and the incidence of tumor rupture and
mended and may in fact complicate treatment spill is also high.
by causing preoperative tumor spill, requiring – Intracaval tumor extension:
whole abdominal radiotherapy. • This occurs in 5 % of cases of Wilms’
• Aspiration cytology is a valuable investigation tumor.
to diagnose Wilms’ tumor but it requires a • This is associated with a 40 % rate of
good pathologist to read it (Fig. 4.51). surgical complications.
• The usual approach in most patients is • Chemotherapy after staging and biopsy
nephrectomy followed by chemotherapy, with is beneficial in reducing the tumor and
or without postoperative radiotherapy. thrombus size.
• Children found to have loss of heterozygosity at – Bilateral Wilms’ tumor (Figs. 4.58, 4.59,
1p and 16q receive more aggressive chemother- 4.60, 4.61, 4.62, and 4.63).
apy because they have a worse prognosis than – SIOP advocates chemotherapy without previ-
do children without this heterozygosity loss. ous laparotomy and biopsy. The NWTSG sug-
• Children younger than age 12 months diag- gests that this approach results in a 1–5 % risk
nosed with perilobar nephrogenic rests have a of treating a benign disease.
markedly increased risk of developing a con- – Chemotherapy without proper surgical
tralateral Wilms’ tumor. staging (e.g., staging by means of imaging
Figs. 4.52 and 4.53 CT-can showing large Wilms Tumors that appear inoperable
Figs. 4.54 and

4.55 CT-scan showing
large left sided Wilms
tumor
Figs. 4.56 and 4.57 Radiological evaluation of a large left Wilms tumor that was treated with preoperative chemo-
therapy showing an excellent response
studies only) may alter the actual initial – A child less than 2 years old and a tumor
stage of the disease by the time of surgery less than 550 g only requires Nephrectomy
and may subsequently alter decisions and observation.
regarding the adjuvant chemotherapy and • Stage II:
radiation therapy, which is based on the – Nephrectomy + abdominal radiation +
surgical staging. 24 weeks of chemotherapy.
• Postoperative chemotherapy and radiotherapy • Stage III:
protocols are based on the surgical staging and – Abdominal radiation + 24 weeks of chemo-
follow the guidelines of the NWTSG. therapy + nephrectomy after tumor shrinkage.
• Stage I: • Stage IV:
– Nephrectomy ±18 weeks of chemotherapy – Nephrectomy + abdominal radiation +
depending on age of the patient and weight 24 weeks of chemotherapy + radiation of
of tumor. metastatic site as appropriate.
Figs. 4.58, 4.59, 4.60, and 4.61 Abdominal CT-scans showing bilateral Wilms tumors
Figs. 4.62 and 4.63 Abdominal CT-scans showing bilat- pearance of Wilms tumor on one side and marked reduc-
eral Wilms tumor before and after chemotherapy. Note the tion of the tumor on the other side
excellent response to chemotherapy with complete disap-
• Stage V: to stage I favorable histology patients.

– Individualized therapy based on tumor – Children with stage II through stage IV dif-
burden. fuse anaplasia, however, represent a higher-
• The management of bilateral Wilms’ tumor risk group.
must be individualized according to the extent – These tumors are more resistant to the che-
of tumor present in both kidneys with a goal to motherapy traditionally used in children
preserving adequate kidney tissue to avoid with Wilms’ tumor (favorable histology),
kidney failure. and require more aggressive regimens.
– The initial procedure should be biopsies of • About 5–10 % of patients with Wilms tumor
both kidneys to establish the diagnosis and present with acquired von Willebrand disease
histological types in both kidneys. at the time of diagnosis.
– Approximately 4 % of cases have different • The reason for this acquired von Willebrand
types between the two kidneys. disease is not known ad several hypothesis
– The patient is treated with chemotherapy and have been postulated including:
restudied by abdominal CT or MRI to evalu- – Absorption of the von Willebrand factor
ate tumor response and determine whether a (vWF) by tumor cells.
surgical procedure would be beneficial. – Hyperviscosity caused by elevated serum
– If considerable tumor persists in both kid- levels of hyaluronic acid.
neys, additional chemotherapy is adminis- – An immunoglobulin G (IgG)–type anti-
tered, and surgery is delayed. body that prevents aggregation of normal
– Radiation therapy is withheld if possible in platelet cells.
these cases to reduce the risk of radiation • The presence of acquired von Willebrand dis-
injury to the remaining kidney tissue. ease in these patients will lead to excessive
– In some patients, the tumor persists in both bleeding during surgery and should be treated
kidneys, and resection of the tumor with preoperatively.
preservation of functioning kidney tissue is • Desmopressin (DDAVP), a drug that promotes
not possible. The only remaining option for the release of vWF from storage sites, is
these rare patients ultimately is removal of recommended.
both kidneys. • If DDAVP is ineffective, cryoprecipitator (a spe-
• Stage I–IV Anaplasia: cific vWF concentrate) should be administered.
– Children with stage I anaplastic tumors can • Management of lung metastasis (Figs. 4.64,
be managed with the same regimen given 4.65, and 4.66):
Figs. 4.64 and 4.65 Abdominal and chest x-ray in a patient with right Wilms tumor and normal looking chest x-ray
and chest CT-scan showing a single secondary in the chest
– A normal chest x-ray during initial evaluation of distant spread or presence of 1p and 16q
does not exclude the presence of pulmonary deletion are treated with 6 weeks of actinomy-
metastasis and a chest CT-scan should be done cin-D, doxorubicin, and vincristine.
as part of their evaluation.
– Children with normal looking chest radiogra- 4.2.10.1 Surgical Management
phy and positive findings on chest CT-scan (Figs. 4.67 and 4.68)
require tissue diagnosis of the lung nodules. • The first step in the treatment of Wilms’ tumor
– It is important to have tissue diagnosis of the is surgical staging followed by radical
lung nodules because several conditions (e.g. nephrectomy, if possible.
histoplasmosis, atelectasis, pseudotumor, • Begin the abdominal exploration through a
intrapulmonary lymph node, pneumonia) can transverse incision.
mimic pulmonary metastases. • The kidney is explored by mobilizing the
– These secondaries can be single or multiple. ipsilateral colon and opening the Gerota
– A biopsy can be performed percutaneously or fascia.
thoracoscopically. • Exploration of the contralateral kidney is cur-
– Single secondaries can be excised totally rently not recommended because of the
while multiple lesions are biopsied. improvement in imaging techniques (com-
– Patients with favorable histology Wilms’ puted tomography [CT] scanning, magnetic
tumor with lung metastasis and no other sites resonance imaging [MRI]).
• If the tumor is unresectable, biopsies are per-
formed and the nephrectomy is deferred until
after chemotherapy, which, in most cases, will
shrink the tumor.
• Radical nephrectomy is the treatment of
choice.
• If bilateral disease is diagnosed, nephrectomy
is not performed, but biopsy specimens are
obtained.
• New protocols in the management of bilateral
Wilms’ tumor are being explored. If the dis-
ease is unilateral, radical nephrectomy and
regional lymph node dissection or sampling
are performed.
Fig. 4.66 Chest CT-scan showing multiple bilateral pul-
monary secondaries in a child with Wilms tumor
Fig. 4.67 A clinical

intraoperative
photograph showing
radical nephrectomy for
Wilms tumor. Note also
the ureter which should URETER
be excised as low as
possible

intraoperative
photograph showing
radical nephrectomy
for Wilms tumor
WILMS’ TUMOR
NORMAL KIDNEY
Stage and histology Surgery Chemotherapy Radiotherapy

Stage I or II favorable Nephrectomy Vincristine, dactinomycin No
histology without loss of
heterozygosity (LOH) 1p
and 16q
Stage I or II favorable Nephrectomy Vincristine, dactinomycin, No
histology with LOH 1p doxorubicin
and 16q
Stage III and IV favorable Nephrectomy Vincristine, dactinomycin, Yes
histology without LOH 1p doxorubicin
and 16q
Stage III and IV favorable Nephrectomy Doxorubicin, Yes
histology with LOH 1p cyclophosphamide, etoposide
and 16q
Bilateral Wilms’ tumor:

• Partial nephrectomy:
– The role of partial nephrectomy remains – With bilateral Wilms’ tumor (6 % of cases),
controversial. surgical exploration, biopsy of both sides,
– Partial nephrectomy may be feasible in and accurate surgical staging (including
only 10–15 % of patients, as most tumors lymph node biopsy of both sides) are
are too large at initial diagnosis. performed.
– The main concern regarding a nephron- – This is followed by 6 weeks of chemother-
sparing procedure is that of local apy that is appropriate to the stage and his-
recurrence. tology of the tumor.
– The NWTS-4 study showed an 8 % local – Reassessment is then performed using
recurrence rate following partial nephrec- imaging studies, followed by definitive sur-
tomy for patients with bilateral disease. gery which can be any of the followings:
– In the presence of bilateral Wilms’ tumors, • Unilateral radical nephrectomy and par-
solitary kidney, or renal insufficiency, partial nephrectomy on the contralateral
tial nephrectomy is a reasonable side.
consideration. • Bilateral partial nephrectomy.
• If inferior vena cava (IVC) thrombus is pres- • Unilateral nephrectomy only, if the
ent, preoperative chemotherapy will reduce response was complete on the opposite
the cavotomy rate by 50 %. side. This approach dramatically
reduces the renal failure rate following 4.2.12 Prognosis and Outcome
bilateral Wilms’ tumor therapy.
– The overall 2-year survival rate is higher • The overall 5-year survival in children with
than 80 % with this approach, and the Wilms’ tumor is estimated to be approxi-
nephrectomy rate drops by 50 % in patients mately 90 %.
with bilateral Wilms’ tumor. • This however is variable and the prognosis is
highly dependent on the stage and treatment
of tumor.
4.2.11 Surgical Complications • Tumor-specific loss-of-heterozygosity (LOH)
for chromosomes 1p and 16q identifies a sub-
• The overall surgical complication rate for set of Wilms’ tumor patients who have a sig-
Wilms’ tumor is approximately 15–20 %. nificantly increased risk of relapse and death.
• Surgical complications may include the • LOH can now be used as an independent prog-
following: nostic factor together with disease stage to
– Small-bowel obstruction (7 %) give intensive treatment.
– Hemorrhage (6 %) • Patients with synchronous bilateral tumors
– Wound infection, hernia (4 %) have a 70–80 % survival rate, whereas those
– Vascular complications (2 %) with metachronous tumors have a 45–50 %
– Splenic and intestinal injury (1.5 %) survival rate.
• Patients with anaplastic Wilms’ tumor have a
worse prognosis compared with favorable his-
tology Wilms’ tumor. The 4-year overall sur-
Currently, Patients with High Risk Wilms’ vival rates are as follows:
Tumor Are Treated as Follows – Stage I: 83 %
• Focal anaplastic stage I–III Wilms’ – Stage II: 83 %
tumors and diffuse anaplastic stage I – Stage III: 65 %
Wilms’ tumors: – Stage IV: 33 %
– Nephrectomy followed by vincris- • Chemotherapy and radiation therapy can
tine, actinomycin-D, and doxorubi- induce second malignant neoplasms.
cin in addition to local radiotherapy. – Most secondary malignant neoplasms
• Focal anaplastic stage IV Wilms’ tumors reported (e.g., bone tumors, breast and thy-
and diffuse anaplastic stage II–III roid cancers) have occurred in irradiated
tumors: areas. Nevertheless, certain chemothera-
– Nephrectomy followed by chemother- peutic agents, including doxorubicin, dacti-
apy including vincristine, actinomy- nomycin, and vincristine, may contribute to
cin-D,doxorubicin,cyclophosphamide, an increased risk for secondary
etoposide, and carboplatin in addition malignancies.
to local radiotherapy • Bilateral, high-stage tumors with unfavorable
• Stage IV diffuse anaplastic Wilms’ histology are associated with a poor prognosis
tumors: in spite of multimodal therapy.
– More aggressive treatment is deliv- • Children with Wilms’ tumor have a minimal
ered; nephrectomy is followed by risk for impaired renal function but bilateral
initial irinotecan and vincristine disease and radiotherapy can further compro-
administration, which in turn is fol- mise the renal function.
lowed by actinomycin-D, doxorubi- • Several cytotoxic agents may damage the liver
cin, cyclophosphamide, carboplatin, of patients treated for Wilms’ tumor, includ-
etoposide, and radiotherapy. ing dactinomycin and radiation induced
hepatitis.
4.2.13 Extrarenal Wilms’ Tumors

Overall Prognosis of Wilms’ Tumor
• Stage I: 98 % 4-year survival; 85 % • Extrarenal Wilms’ tumor is extremely rare
4-year survival if anaplastic. and occurs predominantly in children.
• Stage II: 96 % 4-year survival; 70 % • The presence of an extrarenal Wilms’ tumor
4-year survival if anaplastic. excludes a primary tumor in the kidney.
• Stage III: 95 % 4-year survival; 56 % • Most of the cases that have been reported
4-year survival if anaplastic. involved the retroperitoneum.
• Stage IV: 90 % 4-year survival; 17 % • These tumors can occur in isolation or in
4-year survival if anaplastic. association with other tumors usually
• Stage V: The 4-year survival was 94 % teratomas.
for those patients whose most advanced • The diagnostic criteria necessary to estab-
lesion was stage I or stage II; 76 % for lish the diagnosis include absence of pri-
those whose most advanced lesion was mary kidney tumor and supernumery
stage III. kidney.
• Patients with synchronous bilateral • The origin of Wilms’ tumor is controversial.
tumors have a 70–80 % survival rate • There are hypotheses explaining the origin of
whereas those with metachronous extrarenal Wilm’s tumor such as:
tumors have a 45–50 % survival rate. – From ectopic metanephric blastema: This
• Patients with anaplastic Wilms’ tumor hypothesis is supported by the fact that the
have a worse prognosis compared with majority of these tumors occur in the retro-
favorable histology Wilms’ tumor; the peritoneal region. However the presence of
4-year overall survival rates are 83 %, extra-renal Wilms’ tumor cephalad to kid-
83 %, 65 % and 33 % for stages I, II, III, ney argues against it.
and IV, respectively. – From primitive mesodermal tissue: This
hypothesis is based on the occurrence of
extrarenal Wilms’ tumor in the cervix,
vagina and inguinal canal, where there
• Patients with Wilms’ tumor may develope is a persistent mesonephric duct
hepatic veno-occlusive disease. remnant.
• Congestive heart failure is a well-known compli- – Connheim’s cell rest theory: This is a com-
cation of the administration of anthracyclines. mon hypothesis where cells with persis-
• Radiation therapy can affect pulmonary tent embryonal potential undergo
function. malignant transformation at any point of
• Ovarian and testicular failures can follow time.
whole-abdomen irradiation in childhood or • Reported location of Extrarenal Wilms’ tumor
alkylating agents. include:
• Radiation therapy may affect the growth. – The retroperitoneum
• Relapse of Wilms’ tumor: – Inguinal region
– The lungs are the most common site of – Endocervix, Uterus
relapse. – Epididymis
– This site is affected in more than two thirds – Ovotestis
of children who have a relapse. – Vagina
– The tumor bed is the site of relapse only in – Paraspinal
about one fourth of patients. – Paravesical
– The brain and the bones are not usual sites • The staging and management of extrarenal
of relapse for Wilms’ tumors with favor- Wilms’ tumor are similar to Renal Wilms’
able histology. tumor.
4.3 Mesoblastic Nephroma • Congenital renal neoplasms include, in

decreasing order of frequency:
4.3.1 Introduction – Congenital mesoblastic nephroma
– Wilms tumor
• Mesoblastic nephroma is also called congeni- – Rhabdoid tumor of the kidney
tal mesoblastic nephroma (CMN) or fetal – Clear cell sarcoma
renal hamartoma. – Hamartomas
• This tumor was first described as a separate – Ossifying tumor of infancy
entity by Bolande et al. in 1967. • The Diagnosis is usually made in the antenatal
• Prior to this, it was erroneously confused with period or immediately after birth.
congenital Wilms tumor. • Mesoblastic nephroma is considered generally
• Congenital mesoblastic nephroma (or simply a benign renal tumor.
mesoblastic nephroma) represents 3–10 % of • Among the renal tumors:
all pediatric renal tumors. – Wilms tumor is the most common renal
• It is called congenital because it can be diag- tumor, accounting for 80–85 % of all pedi-
nosed in utero by ultrasound or within the first atric renal tumors.
3 months of life. – Congenital mesoblastic nephroma accounts
• Approximately 50 % occur during the neona- for about 10–15 % of all pediatric renal
tal period and 80 % of cases are reported tumors
within the first month of life. – Rhabdoid tumor of the kidney accounts for
• Congenital mesoblastic nephroma represents 5–10 % of all pediatric renal tumors.
3–10 % of all pediatric renal tumors. It was ini- – Clear cell sarcoma (CCSK) accounts for
tially confused with congenital Wilms’ tumor. 5–10 % of all pediatric renal tumors.
• Mesoblastic nephroma is the most common • The differential diagnosis based on age at pre-
renal tumor identified in the neonatal period sentation and includes the following tumors:
and the most frequent benign renal tumor in – Mesoblastic nephroma: from birth to
childhood. 1 year.
• Mesoblastic nephroma is most commonly – Rhabdoid tumor: from 1 to 2 years of age.
diagnosed in the first 3 months of life. – Clear cell sarcoma of the kidney: from 2 to
• About 90 % present in the first year of life, 3 years of age.
50–75 % of cases occur in young infants, and – Wilm’s tumor: over 3 years of age (Mean
almost none occur after the age of 3 years. 3.5 years).
• It is more common in males than females. • There is an association between CMN and:
• The tumor is considered a hamartoma. – Polyhyramnios with or without hydrops
• It is presumed to originate from proliferating fetalis
nephrogenic mesenchyme. – Hypertension
• Congenital mesoblastic nephroma is almost – Prematurity
always unilateral and is rarely malignant. – Some mesoblastic nephromas are associ-
• It may extend beyond the renal capsule, but ated with paraneoplastic syndromes such as:
rarely metastasizes to distant organs. • Hypertension: This is secondary to
• Metastases to distant organs such as the brain, increased secretion of renin
bone, and lungs have been reported. (hyperreninemia).
• Commonly, mesoblastic nephroma appear as a • Hypercalcemia: This is due to prosta-
large, solitary, predominantly solid, coarse, glandin secretion from the tumor cells.
and echogenic renal mass that may contain • Congenital mesoblastic nephroma arises from
cystic areas. renal mesenchyma and is usually benign.
• Congenital renal tumors comprise 2.5–7 % of • Although CMN is considered a benign tumor,
all perinatal tumors. it could behave aggressively.
4.3 Mesoblastic Nephroma 133
• The tumor lacks renal blastema and neoplastic similar to leiomyomas, hence the name
metanephric elements, thereby differentiating leiomyomatous hamartoma of the
it from Wilms tumor. kidney.
• In addition, it tends to infiltrate the kidney, – Histologically:
rather than form the pseudocapsule of classic • It consists of uniform spindle cells
Wilms tumor. arranged in bundles with scattered foci
• Congenital mesoblastic nephroma is almost of entrapped normal glomeruli and
always unilateral. tubules.
• It may extend beyond the renal capsule, but • The cellular variant:
rarely metastasizes to distant organs. – This type presents later, usually after age
3 months.
– More heterogeneous in appearance on
4.3.2 Classification imaging
– Tends to be larger and presents later in
• Mesoblastic nephroma is a mesenchymal infancy
tumor. – May exhibit aggressive behavior including
• Macroscopically the tumor is a solid unencap- vascular encasement and metastasis
sulated mass which often occurs near the renal – It demonstrates more aggressive imaging
hilum. characteristics, with larger areas of necro-
• It tends to invade the surrounding structures sis and hemorrhage.
and renal parenchyma. – It may invade the perinephric fat and con-
• Haemorrhage and necrosis are infrequent. nective tissues.
• Histologically, it is typically composed of con- – It is associated with a higher rate of local
nective tissue growing between nephrons, usu- recurrence and metastatic disease.
ally replacing most of the renal parenchyma. – On gross examination:
• The classic cytological description of the • The tumor is fleshy with multiple foci of
lesion is that of cellular clusters of spindle necrosis, cystic change, and
cells, mild nuclear pleomorphism, mitotic hemorrhage.
activity and no blastema. – Histologically:
• Pathologically, mesoblastic nephroma are • It consists of spindle cells arranged in a
divided into two types: haphazard sheets with a limited ten-
– The classic variant dency to form bundles as seen in the
– The cellular variants classic form.
• The two types differ in the age at presentation, – The cellular variant may also demonstrate
histologic characteristics, imaging character- the t(12;15) translocation, which is
istics and the biologic behavior of the tumors. diagnostic.
• The classic variant: – On reverse-transcription polymerase chain
– This presents earlier, usually before age reaction (RT-PCR), it may demonstrate the
3 months. ETV6-NTRK3 gene fusion, a feature also
– It usually presents as a solid mass with seen in congenital infantile fibrosarcoma,
small foci of necrosis or hemorrhage. hence the name infantile fibrosarcoma of
– It does not invade the perinephric tissues or the kidney.
the vascular pedicle. • Factors that increase the risk of recurrence and
– It is associated with an excellent outcome metastasis include:
after complete surgical resection of the tumor. – Cellular variant
– On gross examination, the tumor: – Older age at presentation
• Is noncapsulated – Positive surgical resection margins
• Has a whorled trabeculated appearance • Metastases to distant organs such as the brain,
bone, and lungs have been reported. These are – Histologically, the classic form is charac-
seen in cellular variant. terized by rare mitoses and absence of
• The cellular variant has been shown to bear necrosis. Entrapped tubules and/or glom-
the t(12;15)(p13;q25) and ETV6 (chromo- eruli are usually seen at the periphery of the
some 12)-NTRK3 (chromosome 15) gene tumor.
fusion. These combined genes are thought to – Atypical or cellular variant is characterized by
activate tyrosine kinase growth signaling. This a high mitotic index, hypercellularity, and an
gene fusion transcript is also reported in con- atypical growth pattern with necrosis, hemor-
genital or infantile fibrosarcoma rhage, and invasion of adjacent structures.
4.3.3 Epidemiology 4.3.4 Histopathology (Figs. 4.69

and 4.70)
• Mesoblastic nephroma is the most common
renal tumor in neonates and infants and repre- • Mesoblastic nephroma is a solid tumor and
sents 3–10 % of the pediatric renal tumors. mostly these tumors are located near the hilum
• Mesoblastic nephroma is the most common of the kidney and may extensively involve the
renal tumor presenting in the neonatal period renal sinus.
and accounts for approximately 54 % of • Cysts are rarely seen but there may be hemor-
tumors in this age group. rhage and necrosis.
• It was initially described as a benign tumor, • The tumor is usually well circumscribed, but it
but currently a spectrum of mesoblastic may be seen infiltrating the renal parenchyma
nephroma exists: and even the perirenal fat.
– The classic type representing the benign • The cut surface of the tumor specimen shows
disease a yellow-tan tumor with a “whorled” appear-
– The cellular variant representing the ance that is similar to a uterine leiomyoma
aggressive disease (40–60 %) with spindled cell bundles.
– The mixed tumors falling somewhere in the • It is composed of immature renal stromal
middle. cells.
– Mesoblastic nephroma has a slight male • The tumor lacks renal blastema and neoplastic
predominance, with a male-to-female ratio metanephric elements, thereby differentiating
of 1.5:1. it from Wilms tumor.
Figs. 4.69 and 4.70 Clinical photograph of a resected the normal kidney is infiltrated by the tumor and not com-
mesoblastic nephroma. Note the whorled appearance of pressed like Wilms’ tumor. Note also the absence of a
the tumor. Note also the normal kidney tissue. Note that capsule
• The tumor tends to infiltrate the kidney, rather • Cellular mesoblastic nephroma:
than form the pseudocapsule of classic Wilms – This is more cellular than the classical type
tumor. and has a sarcomatous appearance consist-
• There are two pathologic variants of meso- ing of tightly packed cells with frequent
blastic nephroma: mitoses (25–30/10 HPF).
– Classic – Data from the National Wilms Tumor
– Atypical or cellular. Study show that cellular mesoblastic
• The classic type is characterized by rare mito- nephroma is commoner than classic meso-
ses and absence of necrosis. Entrapped tubules blastic nephroma with a ratio of 3:1.
and/or glomeruli are usually seen at the – Cellular mesoblastic nephroma presents a
periphery of the tumor. few months later in life than the classic
• Classic mesoplastic nephroma: mesoblastic nephroma.
– Fascicles and whorls of spindly cells. – Unlike the classic type, cellular mesoblas-
– These cells have the features of secondary tic nephroma may reach a huge size and
mesenchyme, which, in contrast with can weigh more than 1 kg (Fig. 4.71).
those of primary mesenchyme (meso- – Histologically, two types of cells are seen. The
blast), lack the capacity to form epithelial more common cell type is a plump cell with
structures. ample cytoplasm and a vesicular nucleus. The
– Instead, the proliferating cells acquire the less common type is a blue cell, which shows
features of fibroblasts, myofibroblasts, or less cytoplasm and resembles cells of infantile
smooth muscle cells. fibrosarcoma.
– These cells contain vimentin, fibronectin, • The cellular variant has been shown to bear
and sometimes actin, but not keratin or the t (12; 15) (p13; q25) and ETV6 (chromo-
laminin. some 12)-NTRK3 (chromosome 15) gene
– The tumor has irregular borders, with fusion. These combined genes are thought to
bands of tumor extending into surrounding activate tyrosine kinase growth signaling. This
soft tissue. gene fusion transcript is also reported in con-
– It also permeates the adjacent renal paren- genital or infantile fibrosarcoma.
chyma to encircle groups of tubules and
glomeruli.
– Metaplastic tissues are usually found at the
tumor-kidney interface or near entrapped
renal tubules and glomeruli, most com-
monly cartilage.
– Extramedullary hematopoiesis and cuboi-
dal metaplasia may also be present.
– Mitotic figures may be encountered, but
frequent mitoses are more characteristically
seen in cellular mesoblastic nephroma.
• Atypical or cellular variant is characterized
by:
– A high mitotic index.
– Hypercellularity.
– An atypical growth pattern with necrosis,
hemorrhage, and invasion of adjacent
structures. Fig. 4.71 A clinical photograph showing an excised large
– The cellular type accounts for 40–60 % of mesoblastic nephroma that weighed more than one
mesoblastic nephroma cases. kilogram
• Factors that increase the risk of recurrence and • Prematurity and polyhyramnios with or with-
metastasis include: out hydrops fetalis are known to be associated
– Cellular variant. with mesoblastic nephroma.
– Older age at presentation. • Postnatally, although abdominal ultrasound
– Positive surgical margins. and CT-scan are useful in diagnosing meso-
• Metastases to distant organs such as the brain, blastic nephroma, MRI is the most accurate
bone, and lungs have been reported with the imaging modality, as it most accurately depicts
cellular type. the local and regional extent of the tumor.
• There is also a variant of mesoblastic • These radiological investigations although they
nephroma which is cystic. This is called cystic may suggest the most likely diagnosis but can-
mesoblastic nephroma which can be confused not definitively differentiate a mesoblastic
with other congenital cystic lesions of the nephroma from other renal tumors and histologic
kidney. examination is the only definitive diagnosis.
• Polyhydramnios is reported in 71 % of preg-
nancies associated with mesoblastic nephroma.
4.3.5 Clinical Features • The most common clinical presentation is an
asymptomatic abdominal mass.
• The diagnosis of mesoblastic nephroma may • The mass can grow rapidly and attain a large
be made antenatally on ultrasound performed size (Figs. 4.72, 4.73, 4.74, and 4.75).
as early as 18–20 weeks’ gestation. • Hematuria is a rare manifestation of meso-
• Fetal ultrasonography is useful in differentiat- blastic nephroma.
ing a renal mass from hydronephrosis but if • Paraneoplastic syndromes such as hyperten-
the mass is large it may be difficult to deter- sion or hypercalcemia may be present.
mine the origin of the tumor. • Hypertension is thought to be secondary to
• Fetal magnetic resonance imaging (MRI) may increased renin production by the trapped
be more helpful in determining the organ of glomeruli in the tumor.
origin because of the ability to take images in • Hypercalcemia: This is due to prostaglandin
multiple planes. secretion from the tumor cells.
Figs. 4.72 and 4.73 Clinical photographs showing marked abdominal distension secondary to a very large mesoblas-
tic nephroma
Figs. 4.74 and 4.75 Clinical photographs of a very large mesoblastic nephroma that was completely excised. In spite
of the large size there were no secondaries
• Potential intrauterine complications with large

mesoblastic nephroma:
– Abdominal dystocia at birth
– Arterio-venous shunting with subsequent
development of hydrops fetalis.
4.3.6 Investigations
• Complete blood count

• Serum electrolyte, BUN and creatinine
• Live function tests
• Plain radiograph: This may demonstrate a soft
tissue mass displacing bowel. Calcification is
very rarely seen (Figs. 4.76).
• Abdominal Ultrasound:
– This reveals a well-defined mass with low-
level homogeneous echoes.
– The presence of concentric echogenic and
Fig. 4.76 Plain x-ray showing a large soft tissue density
hypoechoic rings can be a helpful diagnos-
occupying almost the whole abdomen
tic feature.
– A more complex pattern due to hemor-
rhage, cyst formation and necrosis can also lesion with variable contrast enhancement.
be seen and tends to favor the cellular – Cystic areas, necrosis, and hemorrhage are
variant. uncommon but can be seen in the cellular
– Color Doppler ultrasound may show variant.
increased vascularity. • Abdominal MRI:
– Antenatal ultrasound may also show evi- – Antenatal abdominal MRI is the most use-
dence of associated polyhydramnios. ful investigation to assess and diagnose
• Abdominal CT-scan (Figs. 4.77 and 4.78): mesoblastic nephroma. This reveals a
– This shows a solid hypoattenuating renal homogenous hypointense renal mass.
Figs. 4.77 and 4.78 Abdominal CT-scan showing a very large right side renal tumor. This was excised and found to
be mesoblatic nephroma. Note the normal looking left kidney
– Postnatal MRI is also useful in outlining 4.4 Clear Cell Sarcoma

the site and size of the tumor properly as of the Kidney (CCSK)
well as its relation to other intra-abdominal
organs. 4.4.1 Introduction
• In the past, clear cell sarcoma of the kidney

4.3.7 Treatment and Prognosis was considered as a subtype of Wilms’ tumor.
• Clear cell sarcoma is now considered a dis-
• The majority of these tumors are benign tinct clinical and histologic entity.
tumors and have a favorable outcome. • In 1970, Kidd initially recognized clear cell
• The cellular variant can at times be sarcoma of the kidney as a distinct clinico-
aggressive. pathologic entity, noting its propensity to
• Surgical resection of congenital mesoblastic metastasize to bone.
nephroma is the treatment of choice and this is • The distinctive histopathologic features of
curative. clear cell sarcoma of the kidney were reported
• Most cases of mesoblastic nephroma are clini- simultaneously in 1978 by Morgan and Kidd,
cally benign. However, there are reports of Marsden et al, and Beckwith and Palmer.
local recurrence in incompletely resected • Clear cell sarcoma of the kidney is also known
tumors, and metastases to the brain, lung, as bone metastasizing renal tumor of child-
heart and bone. hood because of its tendency to metastasize to
– In such cases, patients may be treated with bones.
chemotherapy and/or radiation therapy. • Clear cell sarcoma of the kidney (CCSK), is
• When diagnosed in the first 7 months of life, an uncommon renal tumor of childhood.
the 5-year event-free survival rate is 94 % and • It accounts for 4–5 % of all primary renal
the overall survival rate is 96 %. tumors in childhood.
• Patients at increased risk of recurrence and/or • Approximately 20 new cases are diagnosed
metastasis are those showing incomplete each year in the United States.
resection with positive resection margins, • It is difficult to differentiate clear cell sarcoma
cellular type, and age at diagnosis of more from Wilms’ tumors both clinically and
than 3 months radiologically.
4.4 Clear Cell Sarcoma of the Kidney (CCSK) 139
• Age of presentation of CCSK ranges from • This is followed by the lungs, abdomen, retro-
2 months to 14 years, with a mean age at diag- peritoneum, brain, and liver.
nosis of 36 months. • Unusual soft tissue sites (scalp, epidural,
• Clear cell sarcoma of the kidney is extremely nasopharynx, neck, paraspinal, ovary, abdom-
rare in infants younger than 6 months old. inal wall, and axilla) and other sites (orbit)
• The highest incidence (50 % of the cases) of have also been reported.
clear cell sarcoma of the kidney is in children • Since bone metastases may occur with this
aged 2–3 years. disease, bone scintigraphy or FDG-PET scan
• It occurs more in males than females, with a is recommended and Brain CT scan or MRI
male-to-female ratio of 2.04:1. are part of the workup of these patients.
• CCSK arises from a renal mesenchymal cell • Overall, the prognosis of clear cell sarcoma is
that possesses neural markers. poor when compared with that of patients with
• Grossly, the tumor is soft and well Wilms’ tumors.
circumscribed. • The treatment consists of radical nephrec-
• Histologic analysis show small cells with tomy, chemotherapy, and radiotherapy.
inconspicuous nucleoli and ill-defined cell • The prognosis of CCSK is generally poor, but
membranes and a prominent capillary the development of newer treatment regimens
network. has improved survival and currently the
• The Clinical presentation includes abdominal relapse-free and cancer-specific survival rate
pain, hypertension, and hematuria. for revised stage 1 CCSK is about 90–100 %.
• Radiologically, it is difficult to differentiate this • Currently, the overall survival rate for patients
from Wilms tumor but a sharply demarcated with CCSK is about 83 %.
solid intrarenal mass without intra-vascular
extension is most radiological finding.
• Clear cell sarcoma of the kidney is character- 4.4.2 Pathophysiology
ized by:
– Its propensity to metastasize to bones. • Clear cell sarcoma of the kidney originates
– Poor prognosis. from renal mesenchymal cells with neural
– The sarcomatous nonepithelial nature. markers.
– CCSK may also recur many years after its • It is not associated with intralobar nephro-
initial diagnosis. genic rests.
• The tumor is characterized by its aggressive • CCSK is usually unilateral affecting only one
behavior and is associated with a higher rate kidney and no bilateral cases have been
of relapse and mortality than Wilms tumor. It reported.
may metastasize to the bones, lymph nodes, • At the time of presentation:
brain, liver, and lungs, in some cases long – 25 % of patients presented with stage I tumors
after nephrectomy. – 37 % of patients presented with stage II tumors
• CCSK is an aggressive renal tumor with a – 34 % of patients presented with stage III
unique propensity to metastasize to bone and tumors
brain, as well as lung and abdomen. – 4 % of patients presented with distant
• Only 4–5 % of patients with CCSK present metastases
with distant metastases. • The most common site of metastasis at the
• The most common site of metastasis at the time of presentation in patients with clear cell
time of presentation in patients with clear cell sarcoma of the kidney is the ipsilateral renal
sarcoma of the kidney is the ipsilateral renal hilar lymph nodes.
hilar lymph nodes. • Skip metastases to periaortic lymph nodes
• Bone is the most common site of distant have been reported in patients with clear cell
metastases (15 %). sarcoma of the kidney.
• Bone is the most common site of metastases • Liver function testes

(15 %), followed closely by lung, abdomen, • Prothrombin time and activated partial throm-
retroperitoneum, brain, and liver. boplastin time
• Unusual soft tissue sites (scalp, epidural, • Abdominal ultrasound:
nasopharynx, neck, paraspinal, ovary, abdom- – This is important to define the tumor, its
inal wall, and axilla) and other sites (orbit) origin and extent.
have been reported. – It is also important to evaluate the status of
• Approximately 20 % of documented clear cell the inferior vena cava and any gross exten-
sarcoma of the kidney metastases occurred at sion into the renal vein.
least 3 years after diagnosis; some occurred as – Tumor thrombus in the renal vein is present
long as 10 years later. in approximately 5 % of patients with clear
cell sarcoma of the kidney.
• CT scans of the chest and abdomen:
4.4.3 Clinical Features – To define the origin and extent of the tumor
– To define secondaries in the lymph nodes,
• The clinical manifestations of patients with liver and lugs
clear cell sarcoma of the kidney (CCSK) are • Bone scan is important to exclude
similar to those patients with Wilms tumor. secondaries
• The usual presentation is with an abdominal • Brain CT scan or MRI are also important to
mass that was noticed by the parents or primary detect secondaries
care physician or pediatrician. Sometimes, the
mass is discovered accidently during an abdom-
inal ultrasound that was ordered for something 4.4.5 Histopathology
else. The mass may be discovered by the mother
while dressing or giving bath to the child. • Clear cell sarcoma of the kidney usually pres-
• Other clinical presentations include: ents as a large mass markedly distorting or
– Abdominal pain almost completely replacing the kidney.
– Gross or microscopic hematuria • The tumor can reach a large size with a mean
– Fever tumor diameter of 11.3 cm (2.3–24 cm).
– Hypertension • The mean weight of the kidney tumor is about
• Clinically, the patient has a large palpable uni- 661 g.
lateral abdominal mass. • CCSK is an epicenteric tumor and the renal
• No specific chromosomal translocation or medulla is the most common location.
syndromes have been associated with clear • No case of multicentric tumor was
cell sarcoma of the kidney. identified.
• The proto-oncogene c-kit is overexpressed in • On cut sections of the tumor:
clear cell sarcoma of the kidney but is not – It appears as tan-gray, soft, and mucoid.
accompanied by gene amplification or activat- – There are multiple cystic areas and
ing mutations. sometimes these cysts represent the domi-
• The t(10;17)(q22;p13) and deletion 14q have nant feature.
been described. – Discrete foci of necrosis and hemorrhage
may be present.
• Histologically, clear cell sarcoma of the kid-
4.4.4 Investigations ney shows three components:
– Cord cells:
• CBC • These are small round-to-oval cells with
• Serum electrolytes, BUN and creatinine deceptively bland cytologic features,
levels including mitotic figures.
4.4 Clear Cell Sarcoma of the Kidney (CCSK) 141
– Septal cells: membrane antigen, desmin, S100, factor

• These are spindle-shaped cells along the XIIIa, c-kit, polyclonal carcinoembryonic
fibrovascular septa (fibrovascular septa antigen (CEA), and MAC387.
can be demonstrated more convincingly – Positive staining results for cytokeratin, α 1
using reticulum stain). -antitrypsin, and α 1 -antichymotrypsin
– An intercellular matrix: have also been described.
• This is composed of mucopolysaccha-
ride, which ranges from minute indis-
cernible droplets to large pools 4.4.6 Treatment
imparting the clear appearance of clear
cell sarcoma of the kidney. • The overall survival of children with clear cell
• Depending on the amount, distribution, and sarcoma of the kidney remains considerably
variation in morphology of the 3 components, lower than that of patients with favorable-
CCSK is divided histologically into two types: histology Wilms tumor.
– Classic clear cell sarcoma of the kidney • The overall survival has improved for patients
– Variant clear cell sarcoma of the kidney with clear cell sarcoma of the kidney from
– The classic pattern usually represents the NWTS-3 to NWTS-4 (83 % vs 66.9 % at
predominant pattern in most clear cell sar- 8 year).
coma of the kidney tumors. • This is attributed to the use of chemotherapy
– The classic histologic pattern is character- for prolonged periods.
ized by cord cells arranged in cords, nests, • NWTS-4 showed that patients treated with
or groups surrounded by thin fibrovascular vincristine, doxorubicin, and dactinomycin
septa. A moderate amount of clear intercel- for 15 months had an improved relapse-free
lular matrix separates the cord cells, giving survival rate compared with patients treated
a clear appearance, hence the designation for 6 months (87.5 % vs 60.6 % at 8 year).
clear cell sarcoma of the kidney. • The 8-year relapse-free survival rate for local-
– The most common variant is the myxoid ized clear cell sarcoma of the kidney stages
CCSK. I–III is 88 %, but late relapses have been
– The variant patterns include: reported.
• Myxoid pattern (50 %) • In the NWTS-5 protocol, patients with all
• Sclerosing pattern (35 %) stages of CCSK are treated with the same regi-
• Cellular pattern (26 %) men used in patients who have Wilms tumor
• Epithelioid pattern (trabecular or acinar with diffuse anaplasia (excluding stage I).
type) (13 %) • This treatment consists of:
• Palisading (Verocay body) pattern – A radical nephrectomy
(11 %) – Followed by chemotherapy with cyclo-
• Spindle cell pattern (7 %) phosphamide, etoposide, vincristine, and
• Storiform pattern (4 %) doxorubicin for 24 weeks.
• Anaplastic pattern (2.6 %) – And radiotherapy
– The anaplastic pattern is defined by nuclear – CCSK commonly responds poorly to treat-
hyperchromasia, nuclear gigantism, and ment with vincristine and actinomycin alone,
atypical mitoses. but the addition of doxorubicin to chemother-
– Overexpression of p53 (>75 % of the apy regimens has improved survival rates.
nuclei) has been demonstrated in anaplas- • In the current Children’s Oncology Group
tic clear cell sarcoma of the kidney. protocol (AREN0321), all patients with clear
– The tumor cells usually test positive for cell sarcoma of the kidney, except patients
vimentin and negative for cytokeratin, fac- with stage IV, continue treatment as in
tor VIII–associated antigen, epithelial NWTS-5.
• Patients with stage I who undergo lymph node – Patients with recurrent clear cell sarcoma
sampling do not undergo radiation therapy to of the kidney that involves the brain can be
the tumor bed. treated with ifosfamide, carboplatin, and
• Any patient with stage I who has not under- etoposide (ICE), coupled with local control
gone lymph node sampling is upstaged to consisting of either surgical resection and/
stage II. or radiation.
• Patients with stage IV undergo treatment with • Patients require follow-up evaluation for toxic
irinotecan and vincristine in an upfront win- effects resulting from chemotherapy, radio-
dow approach before treatment with therapy, or both. These include:
cyclophosphamide, etoposide, vincristine, – Cardiomyopathy
doxorubicin, and cyclophosphamide. – Patients are at risk for renal failure because
• Surgical treatment: they have a single kidney
– Radical nephrectomy is the initial treat- – Radiation effects including asymmetry of
ment of choice if the lesion is resectable. the back muscles
– If the tumor is not resectable, a biopsy is – Secondary malignant neoplasms
performed, and chemotherapy is adminis- – Infertility
tered, followed by surgical resection after a – Risk of intestinal obstruction
response has been obtained.
– Patients with clear cell sarcoma of the kid-
ney (CCSK) are treated with combination
chemotherapy. 4.4.7 Prognosis
– The addition of doxorubicin to chemother-
apeutic regimens has been shown to • The prognosis for CCSK has improved with
improve disease-free survival rates. the addition of doxorubicin to chemotherapy
• After completing chemotherapy, patients regimens with a 66 % reduction in overall
should continue to have regular follow up with mortality.
blood and radiographic evaluations on an out- • This is particularly so for low stage tumors,
patient basis. • The reported stage-dependent 6-year survival
• The follow up should be every 1–3 months for is:
the first year, every 3–6 months for the second – 97 % for stage I tumors.
and third years, then yearly thereafter. – 75 % for stage II tumors.
• There is an increase in number of CNS recur- – 77 % for stage III tumors.
rences of clear cell sarcoma of the kidney – 50 % for stage IV tumors.
(CCSK) which should be taken in consider- • Twenty-nine percent of patients with CCSK
ation during follow ups. have lymph node metastases at the time of
• Clear cell sarcoma of the kidney tumors are diagnosis, and bone metastasis is the most
associated with late recurrence; the most com- common form of relapse.
mon site of recurrence is the brain and then the • Metastatic lesions have also been reported in
lung. the liver, brain, soft tissue sites, and lung with
• The patients remain at risk for recurrence after more unusual metastases to the skeletal mus-
2 years posttherapy. Tumors may recur as long cles, testis, and salivary gland.
as 10 years after completion of treatment. • Approximately 20 % of documented clear
• Treatment of patients with recurrent clear cell cell sarcoma of the kidney metastases
sarcoma of the kidney: occurred at least 3 years after initial diagno-
– This depends on the initial chemotherapy. sis; bur relapses of CCSK as many as
– Cyclophosphamide and carboplatin should 10 years after original diagnosis have been
be considered if not used initially. reported.
4.5 Malignant Rhabdoid Tumor of the Kidney 143
4.5 Malignant Rhabdoid Tumor • The age at presentation of malignant rhabdoid

of the Kidney tumor of the kidney overlaps with that noted
for congenital mesoblastic nephroma.
4.5.1 Introduction • It is more common in males with a male to
female ratio of 1.5:1.
• Malignant rhabdoid tumor (MRT) is a rare and • Clinically, patients may develop hypercalcemia
very aggressive renal tumor that occurs mainly secondary to elevated parathormone levels.
in children. • Rhabdoid tumor has the worst prognosis of all
• The term rhabdoid was used due to its similarity renal tumors. It is highly aggressive and
with rhabdomyosarcoma. The tumor cells resem- metastasizes early, with most patients present-
ble muscle cells under the light microscope. ing with advanced disease.
• It was originally described as a variant of • Eighty percent develop metastases, most com-
Wilms’ tumor. monly to the lungs and less often to the liver,
• Malignant rhabdoid tumor was initially abdomen, brain, lymph nodes, or skeleton.
described in 1978 as a rhabdomyosarcomatoid • Survival is poor, with an 18-month survival
variant of a Wilms tumor because of its occur- rate of only 20 %.
rence in the kidney and because of the resem- • A key to the diagnosis is negativity of immu-
blance of its cells to rhabdomyoblasts. nohistochemistry for SWI/SNF-related,
• The absence of muscular differentiation led matrix-associated, actin-dependent regulator
Haas and colleagues to coin the term rhabdoid of chromatin, sub-family B, member 1 INI1
tumor of the kidney in 1981. (SMARCB1).
• It is now recognized as an entity separate from • There is no standard treatment for MRT and prog-
a Wilms tumor. nosis is very poor with published overall survivals
• In contrast to a Wilms tumor, a malignant of 15–36 %, however more recent treatment regi-
rhabdoid tumor of the kidney is characterized mens including surgery, radiotherapy, high dose
by the early onset of local and distant metasta- chemotherapy and autologous stem cell rescue
ses and resistance to chemotherapy. (HDCT/ASCR) may improve survival.
• Malignant rhabdoid tumor of the kidney is a • Malignant rhabdoid tumors occur at other
highly aggressive, has a poor prognosis, and sites outside the kidney including:
tend to occur in children less than 2 years of – The liver
age. – Soft tissues
• Malignant rhabdoid tumor of the kidney is a – Lung
rare, highly aggressive malignancy of early – Skin
childhood and accounts for approximately 2 % – Heart
of pediatric renal malignancies. – The central nervous system
• Malignant rhabdoid tumors of the kidneys are – The cerebellum is the most common loca-
more common in infants. tion for primary intracerebral MRT
• Most patients with malignant rhabdoid tumor • Abnormalities in chromosome 22 (commonly
of the kidney are younger than 2 years of age deletions of the INI1 gene in chromosome 22)
at presentation. are commonly seen in patients with MRT.
• The median age at diagnosis is 10.6 months, • About 10–15 % of patients with MRTs have
with a mean age of 15 months. synchronous or metachronous brain tumors,
• The majority are diagnosed between 6 and many of which are second primary malignant
12 months of age. rhabdoid tumors.
• It occurs exclusively in children, with 60 % • The brain tumors may precede or appear sev-
occurring before the age of 1 year of age, and eral years after the detection of malignant
80 % before the age of 2 years. rhabdoid tumor of the kidney.
• For this reason, brain MRI is part of the tumor.

workup of these patients and a close follow-up • Although mutations or deletions of the
is also important in these patients. SMARCB1/INI1 gene play a role in the devel-
• Malignant rhabdoid tumor of the kidney can opment of malignant rhabdoid tumor, the trig-
be diagnosed in utero. gering mechanisms for these genetic
• The presentation of these patients include: alterations are unknown.
– An abdominal mass • Several cases of familial malignant rhabdoid
– Hypertension tumor were also reported.
– Hypercalcemia • No environmental or infectious associations
– Fever with malignant rhabdoid tumor have been
– Hematuria established.
• The clinical and radiological images charac-
teristics of malignant rhabdoid tumors of the
kidney are similar to those of congenital 4.5.3 Histologic Findings
mesoblastic nephroma, clear cell sarcoma of
the kidney, and Wilms’ tumor. • Grossly, malignant rhabdoid tumor of the kid-
• Whereas the overall survival rate for Wilms ney are heterogeneous, bulky, lobulated, friable,
tumors exceeds 85 %, the survival rate for renal solid, gray-tan masses with areas of necrosis
malignant rhabdoid tumors is only 20–25 %. and hemorrhage (Figs. 4.79, 4.80, and 4.81).
• On microscopic examination, malignant rhab-
doid tumors are characterized by the
4.5.2 Etiology and Pathophysiology followings:
– Sheets or solid trabeculae of tumor cells.
• Malignant rhabdoid tumors frequently contain – The tumor cells are large with vesicular
deletions at chromosome locus 22q11.1. nuclei, prominent cherry-red nucleoli.
• This locus contains the SWI/SNF related, – The tumor cells are characterized by an
matrix-associated, actin-dependent regulator abundant eosinophilic cytoplasm.
of chromatin, subfamily B, member 1 – Many tumor cells have a distinct, pale or
(SMARCB1) gene. hyaline pink intracytoplasmic rhabdoid
• SMARCB1 encodes a member of the human inclusion in the cytoplasm.
SWI/SNF complex. – Mitoses are frequent and necrosis is
• SMARCB1 is presumed to function as a classic common.
tumor suppressor and the primary gene – A subset of tumors may be composed pre-
responsible for malignant rhabdoid tumor dominantly of primitive undifferentiated
development. small round blue cells.
• CNS atypical teratoid/rhabdoid tumors (AT/ – Other patterns described as sclerosing
RT) have deletions of the SMARCB1 gene. (including chondroid), epithelioid, spindled,
• This suggests that rhabdoid tumors of the kid- lymphomatoid or histiocytoid, and vascular
ney and brain are identical or closely related may coexist with the classic pattern.
entities. – Malignant rhabdoid tumor of the kidney
• Moreover, 10–15 % of patients with malignant typically has an infiltrative border with the
rhabdoid tumors have synchronous or surrounding nonneoplastic cortex and renal
metachronous brain tumors, many of which are medulla.
second primary malignant rhabdoid tumors. • The most useful ultrastructural findings
• Germline SMARCB1 mutations were detected include:
in some of these patients. – A large whorl of intermediate filaments in
• This is estimated to occur in approximately the cytoplasm with a diameter of 8–10 nm.
15–30 % of patients with malignant rhabdoid – Dilated rough endoplasmic reticulum
Figs. 4.79, 4.80, and 4.81 Clinical operative photographs showing nephrectomy for malignant rhabdoid tumor of the
kidney. Note the tumor is lobulated, friable, with areas of necrosis and hemorrhage
– Rudimentary cell junctions • Malignant rhabdoid tumor occurs slightly

– Cytoplasmic tonofilamentlike bundles more frequently in males than in females, with
– Immunohistochemical examination: The male-to-female ratio of 1.4:1.
tumor cells are polyphenotypic with con- • The median age at presentation is 10.6 months,
sistent staining for vimentin. with a mean age of 15 months.
– The tumor cells are positive for epithelial • Most patients are younger than 2 years at
membrane antigen and/or cytokeratin. presentation.
– The tumor cells are positive for glial fibril- • The usual presentation is an abdominal mass
lary acidic protein, neuron-specific eno- but the initial manifestation may be due to
lase, smooth muscle actin, desmin, and metastatic disease.
CD99. • It is highly aggressive and metastasizes early,
– Malignant rhabdoid tumor lacks INI1 with up to 80 % of patients presenting with
immunohistochemical staining. metastatic disease, typically to the lungs and
less often to the liver, abdomen, brain, lymph
nodes, or skeleton.
4.5.4 Clinical Features • The mass may be noticed by the parents usu-
ally during clothing or while giving a bath to
• Malignant rhabdoid tumor is a rare tumor. the child.
• It accounts for about 1.6 % of all childhood • Sometimes, the mass is discovered by the pri-
renal tumors. mary care physician or pediatrician.
• The mass may reach a large in size. tumor but is associated with congenital
• Sometimes they present with pain or more mesoblastic nephroma.
commonly fussiness. • Liver function test:
• Gross hematuria is a presenting feature in – These may be abnormal in infants and chil-
approximately 60 % of patients. dren with metastases from a renal malig-
• This is in contrast to patients with Wilms nant rhabdoid tumor.
tumor where only 20 % of patients have gross • No pathognomonic radiological features help
hematuria. distinguishing malignant rhabdoid tumor from
• Fever is a presenting symptom in 50 % of the other renal tumors of childhood.
patients • There are however several features that may
• This is in contrast to patients with Wilms raise the suspicion for malignant rhabdoid
tumor where only 25 % of patients have fever. tumor.
• As many as 20 % of patients with a rhabdoid • Abdominal CT-scan and MRI (Figs. 4.82,
tumor of the kidney have synchronous or 4.83, 4.84, 4.85, 4.86, and 4.87):
metachronous CNS tumors, including both – Malignant rhabdoid tumor typically appears
metastases and second primary cancers. as a large, lobulated mass in the center or
• Hypertension is observed in up to 70 % of periphery of the kidney.
patients. – The margins of the tumor may be sharply
• There may be evidence of focal neurologic defined from the adjacent renal parenchyma,
signs or increased intracranial pressure in or they may be indistinct.
light of the prevalence of synchronous CNS – Tumoral lobules are often separated by
tumors. hypoattenuating areas of hemorrhage or
necrosis.
– Calcification occurs frequently in malignant
4.5.5 Investigations and Diagnosis rhabdoid tumor.
– Malignant rhabdoid tumor–associated calcifi-
• The definitive diagnosis of malignant rhab- cations are often linear or curvilinear, and they
doid tumor (MRT) is by means of histologic may outline tumor lobules
analysis. – This is in contrast to Wilms tumor where cal-
• CBC count: cification is seen in about 10 % only.
– Approximately 55 % of patients with – Calcification is rarely seen in children with
malignant rhabdoid tumor present with a clear cell sarcoma or congenital mesoblastic
hemoglobin level of less than 9 g/dL. nephroma.
– Only 25 % of patients with Wilms tumor – A peripheral, subcapsular, crescent-shaped
are anemic at presentation. fluid collection is often seen in association
• Urinalysis: with malignant rhabdoid tumor.
– Microscopic hematuria is seen in 75 % of – These subcapsular fluid collections may be
patients with malignant rhabdoid tumor. due either to hemorrhage or tumor necrosis.
– Approximately 25 % of patients with malig- – Subcapsular fluid collections are more com-
nant rhabdoid tumors have proteinuria. mon in patients with malignant rhabdoid
• Serum calcium measurement: tumor of the kidney than with the other renal
– As many as 25 % of patients with malig- neoplasms that occur in children.
nant rhabdoid tumor present with – The relative frequency of subcapsular fluid
hypercalcemia. collection in different pediatric renal tumors
– This finding is attributed to the ectopic pro- of the kidney is as follows:
duction of parathyroid hormone-related • Malignant rhabdoid tumor of the kidney
protein by the tumor. (70 %)
– Hypercalcemia is uncommon in Wilms • Wilms tumor (9 %)
Figs. 4.82, 4.83, 4.84, and 4.85 Abdominal MRI showing a left renal tumor. This was resected and found to be malig-
nant rhabdoid tumor of the kidney. Note the mass in the center of the kidney
Figs. 4.86 and 4.87 Abdominal MRI showing a large left renal tumor. Note the peripheral, subcapsular, crescent-
shaped fluid collection
• Mesoblastic nephroma (14 %) unless a CNS tumor is diagnosed.

• Clear cell sarcoma of the kidney (25 %) • Rhabdoid tumors of the kidney appear as
• Chest CT-scan: large, centrally located, heterogeneous soft-
– The lungs remain the most common site of tissue masses, involving the renal hilum with
metastases from malignant rhabdoid tumor indistinct margins.
of the kidney. • Rhabdoid tumors are large and heterogeneous,
– Lungs metastases are seen in 83 % of usually located centrally within the kidney.
patients with metastatic malignant rhab- • They are lobulated with individual lobules
doid tumor at diagnosis. separated by intervening areas of decreased
– The metastases is usually bilateral. attenuation, relating to either previous hemor-
• Abdominal ultrasonography: rhage or necrosis.
– This is important to demonstrate invasion • The histologic diagnosis of malignant rhab-
of the renal vein and/or the inferior vena doid tumor depends on identification of char-
cava in patients with malignant rhabdoid acteristic rhabdoid cells:
tumor. – These are large cells with eccentrically
• Radiological evaluation of the brain is indi- located nuclei and abundant, eosinophilic
cated to exclude the possibility of a synchro- cytoplasm.
nous primary or metastatic brain tumor. • Calcification is relatively common, seen in
• Bone Scan: 20–50 % of cases and is typically linear and
– Bone metastases are present in 5 % of tends to outline tumor lobules.
infants and children with metastatic malig- • Subcapsular fluid accumulation is said to be a
nant rhabdoid tumor at diagnosis. relatively characteristic feature, not often seen
– A bone scan is important to exclude bone in other pediatric renal tumors.
metastases. • The INI1 gene (SMARCB1) on chromosome
• Tissue biopsy is required to make a definitive 22q functions as a classic tumor suppressor
diagnosis of malignant rhabdoid tumor. gene.
• Bone marrow aspiration and biopsy are not • Deletions or LOH of 22q in 49/51 was also
routinely necessary because malignant rhab- found in rhabdoid tumors.
doid tumor rarely metastasizes to the bone • There have been reported cases of a child hav-
marrow. ing both atypical teratoid rhabdoid tumors in
• Lumbar puncture is not routinely indicated the brain as well as rhabdoid tumors of the
kidney. It has been hypothesized that a germ- • To try to improve survival, a new regimen of
line INI mutation may predispose a child to chemotherapy consisting of carboplatin-
these tumors. etoposide alternating with cyclophosphamide
• All rhabdoid tumors share deletions in the was used. This however did not improve
long arm of chromosome 22, mapped to the outcomes.
INI1 gene, believed to be a tumor suppressor. • Recent reports have documented successful
• The following features help differentiate outcomes in patients with metastatic malig-
Malignant rhabdoid tumor of the kidney from nant rhabdoid tumor treated with ifosfamide-
Wilms tumor: carboplatin-etoposide (ICE) or
– Subcapsular fluid collections: a rare find- ifosfamide-etoposide (IE) alternating with
ing in other renal tumors. vincristine-doxorubicin-cyclophosphamide
– Tumor lobules separated by hypoattenuat- (VDC).
ing areas of necrosis or hemorrhage • On the basis of these reports,
– Calcifications cyclophosphamide- carboplatin-etoposide
• More common than in Wilms tumors (CCE) alternating with VDC is the main treat-
• Typically linear distribution outlining ment now.
tumor lobules • Radiation therapy is a cornerstone of treat-
– Vascular and local invasion is more ment for CNS malignant rhabdoid tumor of
common the kidneys.
• High dose chemotherapy with stem cell rescue
are used to treat non-CNS malignant rhabdoid
4.5.6 Treatment and Outcome tumor.
• The prognosis for patients with a rhabdoid
• The treatment of children with malignant tumor of the kidney is much worse than that of
rhabdoid tumor of the kidney is surgical resec- patients with other malignant renal tumors.
tion followed by chemotherapy. • In contrast to a Wilms’ tumor, malignant rhab-
• The tumor should be removed en bloc to avoid doid tumor of the kidney is characterized by:
tumoral spillage into the peritoneal cavity – Early onset of local and distant
because this spillage increases the stage of the metastases.
tumor. If the mass involves the upper pole of – Resistance to chemotherapy.
the kidney, the adrenal gland should be – Whereas the overall survival rate for
removed. Wilms’ tumors exceeds 85 %, the survival
• Lymph nodes from the iliac, para-aortic, and rate for rhabdoid tumor of the kidney is
celiac areas should be sampled, even if they do only 20–25 %.
not appear abnormal. – Gross hematuria is a presenting feature in
• If the tumor is bilateral or unresectable, biopsy approximately 60 % of patients with malig-
should be performed and preoperative chemo- nat rhabdoid tumor of the kidney. By
therapy is started to shrink the tumor and facil- contrast, only 20 % of patients with Wilms’
itate subsequent resection. tumor have gross hematuria.
• Chemotherapy for malignant rhabdoid tumor – Fever is a presenting symptom in 50 % of
of the kidney was historically based on ther- patients with a malignant rhabdoid tumor
apy for a Wilms’ tumor. of the kidney, compared with 25 % of
• This included vincristine, actinomycin, and patients with a Wilms’ tumor.
doxorubicin with or without – Hypertension is observed in up to 70 % of
cyclophosphamide. patients with malignant rhabdoid tumor of
• With these agents, the estimated survival rate the kidney.
for patients with malignant rhabdoid tumor of • Malignant rhabdoid tumor of the kidney is a
the kidney was only 23 %. rapidly progressive tumor, with most deaths
occurring within 12 months of presentation. – 8.8 % for patients aged 0–5 months
• The most common sites of metastasis at pre- – 17.2 % for patients aged 6–11 months
sentation are: – 28.6 % for patients aged 12–23 months
– The lungs – 41.1 % for patients aged 24 months or older
– Abdominal lymph nodes • High-stage (stage III/IV) disease is correlated
– Liver with an adverse outcome.
– Brain • The survival of patients with malignant rhab-
– Bone doid tumor in NWTS was as follows:
• Malignant rhabdoid tumor of the kidneys has – Stage I (33.3 %)
the worst prognosis of all malignant renal – Stage II (46.9 %)
tumors. – Stage III (21.8 %)
• Infants and children with malignant rhabdoid – Stage IV (8.4 %)
tumors of the kidneys have aggressive disease, – Stage V (0 %)
typically with distant tumor spread at
diagnosis.
• Frequently, they die early, an 86 % mortality 4.6 Renal Cell Carcinoma
rate (within 1–2 years) and 90 % tumor relapse in Children
despite intense multi-drug chemotherapy.
• As many as 20 % of patients with a malignant 4.6.1 Introduction
rhabdoid tumor of the kidney have synchro-
nous or metachronous CNS lesions, including • Renal cell carcinoma (RCC) is also known as
both metastases and second primary cancers. hypernephroma, Grawitz tumor, and renal
• Mutations or deletions of the SMARCB1/INI1 adenocarcinoma.
gene play a role in the development of malig- • It originates in the lining of the proximal con-
nant rhabdoid tumor. voluted tubules.
• In 1883, Paul Grawitz was the first to describe
the morphology of small, yellow renal tumors.
4.5.7 Mortality/Morbidity • In 1894, Otto Lubarsch, coined the term hyper-
nephroid tumor, which was amended to hyper-
• The overall survival rate for patients with nephroma by Felix Victor Birch-Hirschfeld.
malignant rhabdoid tumor enrolled in NWTS • Foot and Humphreys introduced the term
1–5 was only 23.2 %. Renal Celled Carcinoma to emphasize its ori-
• Most patients present with stage III or IV gin from the renal tubules.
disease. • Fetter modified the term to the now widely
• Patients with germline mutations of SMARCB1 accepted term Renal Cell Carcinoma.
likely manifest disease at an earlier age, with a • In 1959, Oberling et al. described convincing
high risk of progression and inferior histological evidence that RCC arise from the
prognosis. epithelial cells of the renal convoluted tubules.
• Malignant rhabdoid tumor is a rapidly pro- – They found that the tumor cell cytoplasm
gressive tumor, with most deaths occurring contained numerous mitochondria and
within 12 months of presentation. deposits of glycogen and fat.
• The most common sites of metastasis at pre- – They identified cytoplasmic membranes
sentation are the lungs, abdominal lymph inserted perpendicularly onto basement
nodes, liver, brain and bone. membrane with occasional cells containing
• A young age at diagnosis is strongly associ- microvilli along the free borders.
ated with an adverse outcome. • RCC is the most common renal tumor in
• The 4-year event-free survival rates according adults, responsible for approximately 90–95 %
to age at diagnosis were: of cases.
4.6 Renal Cell Carcinoma in Children 151
• Renal cell carcinoma represents 2 % of malig- • Calcification or high-density areas on CT have

nant tumors in adults and is the third most fre- been reported in 14–28 % of RCCs in
quent tumor of the urinary tract after prostate children.
and bladder tumors. • So far, no treatment protocols have been
• Renal cell carcinoma usually occurs in the age defined for children with RCC.
range of 50–70 years. • Surgery is the mainstay of treatment and
• On the other hand, in pediatric ages, only 2–3 % results in cure when the tumor is localized and
of malignant renal tumors are proved to be RCC. completely resected.
• Whereas the peak of incidence in Wilms’ • The importance of radiotherapy and immuno-
tumor occurs around 3 years of age, RCC therapy is not clear and different chemotherapy
presents between 9 and 15 years of age. regimens showed only minimal benefits when
• Renal cell carcinomas are rare in children, and tested in clinical trials.
they show significant differences in their his- • Tumor staging is the most important prognos-
tology and pathogenesis when compared to tic factor.
those seen in adults. • The overall 5-year survival is approximately
• The incidence of RCC increases with age. 60 % and patients with stage IV has the worst
• The incidence of renal cell carcinoma is esti- prognosis.
mated in 0.1–0.3 % of all tumors and 1.8–6.3 % • Radical nephrectomy associated with regional
of all malignant renal tumors in childhood. lymphadenectomy is the best treatment for
• Recent studies showed that the RCC corre- RCC in childhood.
sponds to:
– 1.4 % of renal tumors in patients under
4 years old 4.6.2 Histopathology
– 15.2 % of renal tumors in patients between
5 and 9 years • The gross and microscopic appearance of
– 52.6 % of renal tumors in patients from 10 renal cell carcinomas is highly variable.
to 15 years old • Gross features:
• In the pediatric age group, RCC is seen in – A yellowish, multilobulated tumor in the
patients with Von Hippel-Lindau disease, renal cortex, which frequently contains
which is associated with retinal and central areas of necrosis, hemorrhage and scarring.
nervous system hemangioblastomas, pheo- – The tumor compresses the surrounding
chromocytomas, and pancreatic neuroendo- parenchyma, producing a pseudocapsule.
crine tumors. – Most translocation-RCC and papillary
• RCC is generally symptomatic at diagnosis, RCC are circumscribed, single lesions.
and most children with RCC present with – Multifocality in pediatric RCC is unusual
more locally advanced disease. and when present may suggest an underly-
• Generally, there is no sex predominance for ing syndrome, such as tuberous sclerosis or
RCC in children unlike in adults, in which the von Hippel-Lindau disease.
tumor predominates in males. – Renal medullary carcinomas have a strik-
• The most common form of presentation of ingly infiltrative growth pattern typically
RCC in children is macroscopic hematuria involving the medulla.
and abdominal or flank pain. – Neuroblastoma-associated oncocytic
• Other less frequent symptoms are palpable RCCs are often multifocal or bilateral.
abdominal mass, anemia, and fever. • Microscopic Features:
• RCC is diagnosed as a solid mass with US and – There are four major histologic subtypes of
CT. However, it is generally difficult to dif- renal cell cancer:
ferentiate it from Wilms’ tumor before surgery • Clear cell (conventional RCC, 75 %)
in children. • Papillary (15 %)
• Chromophobic (5 %) • Renal Medullary Carcinomas:

• Collecting duct (2 %) – These are usually composed of high-grade
• Sarcomatoid changes can be observed within epithelial cells with acidophilic cytoplasm,
any RCC subtype and are associated with arranged in a tubular, often cribriform
more aggressive clinical course and worse architecture.
prognosis. – They occasionally are solid or sarcomatoid.
• The tumor cells are quite large, atypical, and – Characteristic microscopic features include
polygonal. desmoplasia and an acute inflammatory
• They can be arranged in papillae, tubules or reaction.
nests. – The nuclei are large with prominent nucle-
• The cells often contain large amounts of clear oli in most cases.
to variably eosinophilic cytoplasm and pos- – The cells contain prominent eosinophilic
sess distinct cell borders separated by thin cytoplasm with occasional rhabdoid-like
fibrovascular septa. cytoplasmic inclusion.
• The most common cell type exhibited by renal – The nucleoli are often prominent.
cell carcinoma is the clear cell, which is charac- • Post-neuroblastoma renal cell carcinomas:
terized by high lipid content in the cytoplasm. – These are single, bilateral, or multifocal
• The clear cells are thought to be the least tumors.
likely to spread and usually respond more – They are composed of solid and occasion-
favorably to treatment. ally papillary cells with oncocytoid fea-
• Most of these tumors however, contain a mix- tures and cellular heterogeneity.
ture of cells. – Many cells contain copious eosinophilic
• Small psammomatous calcifications are vari- cytoplasm with high nuclear grade, but oth-
ably present. ers may lack these features.
• The majority have a Furman nuclear grade of • In 1982, Fuhrman recommended histologic
3, with easily identified nucleoli. grading for RCC.
• Tumors containing the ASPL-TFE3 pheno- • This is based on the microscopic morphology
type tend to have abundant, voluminous cyto- of a neoplasm with hematoxylin and eosin
plasm that often contains cytoplasmic granules (H&E staining).
and eosinophilic bodies. • This system categorizes renal cell carcinoma
• Tumors with PRCC-TFE3 gene fusion often into four grades based on nuclear characteris-
have less abundant cytoplasm, are arranged tics as follows:
more compactly, contain fewer calcifications, – Grade I:
and display lower nuclear grades. • Nuclei appear round and uniform, 10 μm;
• Papillary RCCs: nucleoli are inconspicuous or absent.
– Are composed of cells arranged in tubular – Grade II:
and papillary configurations. • Nuclei have an irregular appearance
– Often contain foamy macrophages. with signs of lobe formation, 15 μm;
– Are typically encapsulated, although the tumor nucleoli are evident.
often penetrates its fibrous pseudocapsule. – Grade III:
– Two types of papillary RCC are identified • Nuclei appear very irregular, 20 μm;
within the WHO classification. nucleoli are large and prominent.
• Type 1 tumors are composed of cuboi- – Grade IV:
dal cells with little cytoplasm arranged • Nuclei appear bizarre and multilobated,
in a single layer. 20 μm or more; nucleoli are prominent.
• Type 2 tumors contain pseudostratified • Nuclear grade is believed to be one of the
cells with higher nuclear grade and typi- most imperative prognostic factors in patients
cally more eosinophilic cytoplasm. with renal cell carcinoma.
4.6.3 Classification • Up to 25 % of pediatric RCC cannot be readily

classified due to atypical features.
• Pediatric renal cell carcinomas (RCC) account • Translocation-RCC may occur following che-
for approximately 2–3 % of all pediatric renal motherapy for other diseases.
tumors. • Papillary RCC comprises approximately 30 %
• RCC arises from the cells of the proximal of the total.
renal tubular epithelium. • Papillary RCC in children may arise in the set-
• It is considered an adenocarcinoma. ting of pre-existing neoplasms, including
• In 1826, Koenig published the first classifica- Wilms tumor, metanephric adenoma, and
tion of renal tumors based on macroscopic metanephric adenofibroma.
morphology. He divided them into four • True clear cell RCC are extraordinarily rare in
forms: childhood.
– Scirrhous • Conventional clear cell RCC comprises
– Steatomatous 6–20 % of the total.
– Fungoid • Renal medullary carcinoma is a highly aggressive
– Medullary tumor arising in patients with the sickle cell gene.
• There are two subtypes of renal cell • Oncocytic RCC had been identified in patients
carcinoma: previously diagnosed with neuroblastoma.
– Sporadic • Pediatric RCC differ in histologic appearance
– Hereditary and genetic features from those seen in adults.
– Both subtypes are associated with muta- – The most common are the Xp11 (TFE3)
tions in the short-arm of chromosome 3, translocation-RCC (20–40 % of total).
with the implicated genes being either – TFE3 translocations involving a multitude
tumor suppressor genes (VHL and TSC) or of variant partners.
oncogenes (like c-Met). – Translocations involving chromosome 17
• RCCs is a heterogeneous group of tumors and [t(X;17)(p11.2;q25), ASPL-TFE3 fusion]
have been classified into five subtypes based and chromosome 1 [t(X;1)(p11.2;q21),
on the location within the nephron in which PRCC-TFE3 fusion].
the tumors originate. – Contemporary investigation of pediatric
– Clear-cell RCCs RCC has demonstrated that a large percent-
– Papillary RCCs age of these tumors bear cytogenetic
– Chromophobe RCCs translocations involving the MiT family of
– Collecting duct carcinomas transcription factors.
– Unclassified RCCs
• The most common subtypes of RCC seen
preferentially in children are: 4.6.4 Staging
– The translocation-associated renal cell
carcinoma • The staging of renal cell carcinoma is the most
– Papillary renal cell carcinoma important factor in predicting its prognosis.
– Renal medullary carcinoma • There are several staging systems for renal
– Oncocytic renal cell carcinoma following cell carcinoma.
neuroblastoma • Staging can follow the TNM staging system
• The histological diagnosis of renal cell car- based on:
cinoma is made difficult by the consider- – T: The size and extent of the tumor
able heterogeneity within and overlap – N: Involvement of lymph nodes
between each of the above subtypes and by – M: Metastases
similarities to other pediatric renal • It should be noted that tumor size, as mea-
neoplasms. sured in greatest dimension, is a critical fea-
ture of the TNM staging system most • Tumor that has spread directly through
commonly utilized in the evaluation of RCC. the fatty tissue and the fascia ligament-
• Staging can also follow the stage grouping like tissue that surrounds the kidney.
into stage I–IV. • Involvement of more than one lymph
– Stage I: Tumor limited to kidney, <2.5 cm node near the kidney.
in diameter • Involvement of any lymph node not near
– Stage II: Tumor limited to kidney, >2.5 cm the kidney.
in diameter • Distant metastases, such as in the lungs,
– Stage III: Tumor extends into renal vein, bone, or brain.
inferior vena cava, and perinephric tissue • At diagnosis, 30 % of renal cell carcinomas
or adrenal glands but does not traverse have spread to the ipsilateral renal vein, and
Gerota fascia; nodal metastases <2 cm in 5–10 % have continued into the inferior vena
diameter cava.
– Stage IV: Tumor extends beyond Gerota
fascia or nodal metastases >2 cm in diam-
eter margins and no capsule 4.6.5 Clinical Features
• Staging of Renal Cell Carcinoma was also
based on a different group staging into stage • The clinical presentation include:
I–IV. – Hematuria (35–40 %)
– Stage I: – Flank pain (40–50 %)
• Tumor of a diameter of 7 cm (approx. – Abdominal mass (25–35 %)
23⁄4 in.) or smaller, and limited to the – Loss of appetite and weight loss (33 %)
kidney. No lymph node involvement or – Fever (20 %)
metastases to distant organs. – Hypertension (20 %)
– Stage II: – Anemia
• Tumor larger than 7.0 cm but still lim- – Night sweats
ited to the kidney. No lymph node – Malaise, fatigue and generally feeling
involvement or metastases to distant unwell
organs. – Left varicocele in males
– Stage III: • The classic triad of RCC is seen in 10–15 % of
• Tumor of any size with involvement of a patients and include:
nearby lymph node but no metastases to – Haematuria
distant organs. – Flank pain
• Tumor of this stage may be with or with- – Abdominal mass
out spread to fatty tissue around the kid- • Children with RCC mostly present with more
ney, with or without spread into the large locally advanced disease.
veins leading from the kidney to the heart. • RCC commonly metastasize to the lymph
– Stage IV: nodes, lungs, liver, adrenal glands, brain or
• Tumor with spread to fatty tissue around bones.
the kidney and/or spread into the large • Metastases occur in:
veins leading from the kidney to the – Lungs (40–65 %)
heart, but without spread to any lymph – Liver (35–57 %)
nodes or other organs. – Bones (10–42 %)
• Tumor with spread to fatty tissue around – Bladder, brain or pleura (7–15 %)
the kidney and/or spread into the large • Renal cell carcinoma is one of the cancers
veins leading from the kidney to the most strongly associated with paraneoplastic
heart, but without spread to any lymph syndromes (PNS), most often due to ectopic
nodes or other organs. hormone production by the tumor.
• These are seen in about 20 % of patients and • Imaging studies demonstrate a large solid
include: intra-renal mass that typically involves the
– Hypercalcemia renal sinus.
– Polycythemia • The mass replaces a large portion of renal
– Thrombocytosis parenchyma and may contain cystic, hemor-
– Secondary amyloidosis rhagic, and necrotic regions.
• Several factors contribute to the outcome of • There is distortion of the normal renal archi-
RCC and these include: tecture and formation of a pseudocapsule.
– Patient age • There is a higher frequency of calcification in
– Tumor size renal cell carcinoma (25 %) than in Wilms
– Histological pattern tumor (9 %).
– Vascular invasion
• The overall survival rate of pediatric RCC is
around 63 % and it is different according to 4.6.7 Management
the stage at diagnosis:
– Stage I (92.4 %) • The treatment depends on several including:
– Stage II (84.6 %) – Stage of renal cell carcinoma
– Stage III (72.7 %) – Organs and parts of the body affected/
– Stage IV (13.9 %) unaffected
• Most recurrences and deaths usually occur – Type of renal cell carcinoma
within the first 2 years after diagnosis, – Pre-existing or comorbid conditions
although late recurrences are frequent and – Overall health and age of the person
long term follow up is important. • Radical nephrectomy (removing the entire
• Renal cell carcinoma is associated with von affected kidney together with Gerota’s fascia,
Hippel–Lindau syndrome, in which the tumors the adrenal gland, and the regional lymph
tend to be multiple and manifest at a younger nodes) is the treatment of choice.
age. • The precise role of lymph node dissection is
• This syndrome must be ruled out in pediatric still controversial.
patients diagnosed with renal cell carcinoma, • Geller and Dome reported a 72.4 % disease
especially when the tumor is bilateral. free survival in patients with RCC and posi-
tive nodal disease. Among those with positive
nodes who underwent adjuvant chemotherapy
4.6.6 Investigations or radiotherapy, no improvement in disease-
free or overall survival was noted. They con-
• Urine analysis cluded that lymphadenectomy in the absence
• Complete blood cell count of clinical or radiographic suspicion for nodal
• Liver function testes involvement confers no benefit.
• Serum electrolytes, BUN and creatinine • Prior to this, it is important to note that the
• Pelvic and abdominal CT scans other kidney must be fully functional.
• Ultrasound • Nephron-sparing partial nephrectomy is used
• MRI scans when the tumor is small.
• Intravenous pyelogram (IVP) or renal • The presence of metastasis is not a contraindi-
angiography cation to nephrectomy and if the metastasis is
• Radiologically, RCC is indistinguishable from small this can also be surgically removed.
Wilms tumor, though it tends to be smaller at • Chemotherapy and radiotherapy are not as
presentation. successful in treating RCC.
• The tumor invades locally with spread to adja- • Adjuvant chemotherapy has not been found to
cent retroperitoneal tissue. be beneficial in renal cell carcinoma.
• Neoadjuvant chemotherapy has been shown to • Respiratory side effects: Coughing, dif-
decrease the size and stage of RCC and this ficulty in breathing
allow it to be surgically removed. This may be • Cardiovascular side effects:
useful in those with large non resectable Hypertension
tumors but the effectiveness of this approach • Neurological side effects: Intracranial
is still being assessed. hemorrhage, thrombosis in the brain
• Immunotherapy with interferon or interleukin • Skin and mucus membranes side effects:
for the treatment of advanced RCC have been Rashes, hand-foot syndrome, stomatitis
reported, but the benefits of these are uncer- • Bone marrow suppression
tain in children. • Renal side effects: Impaired kidney
• The role of new agents such as tyrosine kinase function
inhibitors is not well established in children • Fatigue
with RCC. – Radiotherapy and chemotherapy are
• Metastatic renal cell carcinoma: more commonly used to treat metastatic
– Metastatic renal cell carcinoma has a poor RCC.
prognosis. – These are not curative but are useful to
– The tumor is extremely resistant to chemo- relief symptoms related to the metastasis.
therapy, rendering metastatic disease diffi-
cult to treat.
– 25–30 % of patients with RCC have meta- 4.6.8 Prognosis
static spread at the time of diagnosis.
– The most common sites for metastasis are • The prognosis for renal cell carcinoma is
the lymph nodes, lung, bones, liver and brain. largely influenced by a variety of factors,
– The 5 year survival rate for metastatic renal including:
cell carcinoma remains under 10 % and – Tumor size
20–25 % of these patients remain unre- – Degree of invasion
sponsive to all treatments and the disease – Metastasis
progress rapidly. – Histologic type
– Interleukin-2 is considered a standard treat- – Nuclear grade
ment for those with advanced renal cell • The prognosis is influenced most by the stage
carcinoma. at presentation, with an overall survival rate of
– Other new treatments specifically designed approximately 64 %.
for metastatic renal cell carcinoma include: • Renal cell carcinoma does not generally
• Sunitinib respond to chemotherapy or radiation.
• Temsirolimus • For those that have tumor recurrence after sur-
• Bevacizumab gery, the prognosis is generally poor.
• Sorafenib
• Everolimus
• Pazopanib 4.7 Angiomyolipoma
• Axitinib of the Kidney
– These new treatments inhibit the growth of
new blood vessels in the tumors, slow the 4.7.1 Introduction
growth and in some cases reduce the size of
the tumors. • Angiomyolipomas are the most common
– Side effects are common with these treat- benign tumor of the kidney.
ments and include: • They are classically composed of blood ves-
• Gastrointestinal side effects: Nausea, sels, smooth muscle cells and fat cells.
vomiting, diarrhea, anorexia • It has an incidence of about 0.3–3 %.
4.7 Angiomyolipoma of the Kidney 157
• About 80 % of cases are sporadic and these are • Almost all classic angiomyolipomas are benign.
most commonly found in middle-aged women • They have the risk of rupture with bleeding or
(mean age of presentation 43 years). secondary damage/destruction of surrounding
• There is a strong female predilection (F: M of structures as they grow.
4:1) in sporadic angiomyolipomas. • There is a special variant called an epithelioid
• The remaining 20 % are seen in association angiomyolipoma.
with tuberous sclerosis, although they have – This is composed of more plump, epithelial
also been described in Von Hippel-Lindau looking cells, often with nuclear atypia.
syndrome (VHL) and neurofibromatosis type – These have a risk of malignant behavior.
1 (NF1). – They mimic renal cell carcinoma.
• In patients with tuberous sclerosis, 67–85 % – Metastases from this type have also been
will have renal angiomyolipoma by around described.
10 years of age.
• In these cases they present earlier (usually
identified by the age of 10 years), are larger, 4.7.3 Classification
fat-poor and are far more numerous.
• Angiomyolipomas are strongly associated • Angiomyolipomas are known as a PEComa,
with tuberous sclerosis. from the initials of perivascular epithelioid
• Patients with tuberous sclerosis tend to have cell.
several angiomyolipomas affecting both • They consist of perivascular epithelioid cells
kidneys. (cells which are found surrounding blood ves-
• Angiomyolipomas are also commonly found sels and which resemble epithelial cells).
in women with the rare lung disease • In the past, these tumors were considered as
lymphangioleiomyomatosis. hamartomas (benign tumors consisting of
• They can spontaneously hemorrhage, which cells in their correct anatomical location but
can be fatal. forming a disorganized mass).
• The classic microscopic features of angio- • They were also considered as a choristoma
myolipoma is myoid cells with clear cyto- (benign tumors consisting of normal cells but
plasm spinning off of large vessels in a in the wrong location).
background of mature fat. • Angiomyolipomas are considered as mesen-
• Angiomyolipomas are caused by mutations in chymal tumors composed of varying propor-
either the TSC1 or TSC2 genes, which govern tions of vascular cells, immature smooth
cell growth and proliferation. muscle cells and fat cells.
• Angiomyolipomas are usually benign but they • These three components respectively give
may grow in size to an extent that the kidney rise to the components of the name: angio-,
function is impaired or leads to hemorrhage. myo- and lip-. The -oma suffix indicates a
tumor.
• Angiomyolipomas are typically found in the
4.7.2 Histopathology kidney but have also been found in the liver
and less commonly the ovary, fallopian tube,
• Angiomyolipomas are members of the peri- spermatic cord, palate and colon.
vascular epithelioid cells tumour group • Angiomyolipomas occur in young women
(PEComas). with lymphangiomyomatosis without other
• They are composed of variable amounts of stigmata of tuberous sclerosis.
three components: • Angiomyolipoma is also associated with neuro-
– Blood vessels (-angio) fibromatosis and von Hippel–Lindau syndrome.
– Plump spindle cells (-myo) • In children, angiomyolipomas are rare in the
– Adipose tissue (-lipo) absence of tuberous sclerosis.
• Eighty percent of children with tuberous scle- – A palpable mass

rosis may be expected to develop angiomyoli- – Flank pain
pomas by the age of 10 years. – Urinary tract infections
• There are two types of angiomyolipoma: – Hematuria
– Sporadic (isolated) angiomyolipoma – Renal failure
• This accounts for 80 % of the cases. – Hypertension
• Usually solitary.
• The mean age at presentation is 43 years.
• It is four times more common in women 4.7.5 Investigations
than in men.
• 80 % of the cases involve the right • CBC
kidney. • Electrolytes, BUN and creatinine
– Angiomyolipoma associated with tuberous • PT and PTT
sclerosis • Abdominal ultrasound:
• This accounts for 20 % of the cases. – This reveals hyperechoic lesions located in
• The lesions are typically larger than iso- the renal cortex and with posterior acoustic
lated angiomyolipomas. shadowing.
• They are often bilateral and multiple – In those with tuberous sclerosis, angio-
• They occur equally in males and females myolipomas may be so numerous that the
• Angiomyolipomas occur in 80 % of entire kidney is affected, appearing echo-
patients with tuberous sclerosis. genic with loss of normal cortico-medullary
differentiation.
• Abdominal CT-scan:
4.7.4 Clinical Features – This reveals lesions involving the renal cor-
tex and demonstrate macroscopic fat (less
• Angiomyolipomas are often found inciden- than -20 HU).
tally when the kidneys are imaged for other – It is important to realize that a proportion
reasons, or as part of screening in patients of angiomyolipomas are fat-poor.
with tuberous sclerosis. – This is seen in those with tuberous
• Symptomatic presentation is most frequently sclerosis.
with spontaneous retroperitoneal hemorrhage. – Calcification is rare in these tumors.
• The risk of bleeding being proportional to the • Abdominal MRI:
size of the lesion (>4 cm diameter). – MRI is excellent to diagnose angiomyoli-
• Shock due to severe hemorrhage from rupture pomas because of their high fat content.
is described as Wunderlich syndrome. – It can be difficult to distinguish a fat-poor
• An angiomyolipoma larger than 5 cm and those angiomyolipoma from a renal cell
containing an aneurysm pose a significant risk carcinoma.
of potentially life-threatening rupture. – The presence of fat is not pathognomonic
• Sometimes, the renal angiomyolipomas affect of angiomyolipomas and it is important to
both kidneys to the extent that the renal func- note that rarely renal cell carcinomas may
tion is impaired leading to chronic renal dis- have macroscopic fat components.
ease and renal failure. – The absence of calcification on CT-scan or
• The retroperitoneal hemorrhage causes sudden MRI favors the diagnosis of
pain, accompanied with nausea and vomiting. angiomyolipomas.
• Up to 20 % of those with who present with ret- • Angiography:
roperitoneal hemorrhage will be in shock. – Angiomyolipomas are hypervascular
• Patients may also present with numerous other lesions demonstrating often characteristic
symptoms and signs including: features:
4.8 Renal Lymphoma 159
• Micro- or macro-aneurysms to preserve as much kidney tissue as possible

• Sharply marginated when removing any lesion.
• Dense early arterial network • Large angiomyolipomas are treated by embo-
• Late whorled appearance lization which reduces the risk of hemorrhage
• Absent AV shunting and can also shrink the lesion.
• A side effect of this treatment is postembolisa-
tion syndrome.
4.7.6 Treatment and Prognosis • Post-embolization syndrome usually lasts for
few days and includes:
• Small angiomyolipomas found incidentally – Severe abdominal pain
usually require no therapy. – Fever
• These should be followed-up to assess for – Nausea and vomiting
growth.
• Very small solitary angiomyolipomas
(<20 mm) do not require follow-up due to 4.8 Renal Lymphoma
their slow growth.
• Large angiomyolipomas and symptomatic 4.8.1 Introduction
angiomyolipomas should be treated electively
by: • Primary Renal lymphomas (PRL) are defined
– Embolization as lymphomas arising in the renal parenchyma
– Partial nephrectomy and not invasion from an adjacent
• Angiomyolipomas that present with retroperi- lymphomatous mass or as a part of dissemi-
toneal hemorrhage are treated with emergency nated disease.
embolization and nephrectomy should be • In 1980, Coggins reported the first patient
avoided unless no interventional radiological diagnosed with a PRL.
facility is available. • Primary renal lymphoma is very rare.
• Angiomyolipomas smaller than 4 cm in diam- • PRL accounts for 0.7 % of all extranodal lym-
eter are typically asymptomatic; those larger phomas and represents less than 1 % of all
than 4 cm in diameter are more likely to spon- renal tumors.
taneously hemorrhage, leading to flank or • Lymphomatous involvement of the kidney is
abdominal pain, hematuria, or even severe often seen as a part of disseminated disease.
life-threatening hemorrhage. • PRL is a rare disease in which the etiology and
• Severe retroperitoneal hemorrhage has been pathogenesis are unclear.
termed Wunderlich syndrome. • The kidneys are involved in 12 % of children
• Rarely, angiomyolipoma may become locally with non-Hodgkin’s lymphoma.
aggressive and invade neighboring structures.
Extension into the inferior vena cava and
regional lymph nodes has been described. 4.8.2 Etiology and Pathogenesis
• The recent literature advocates US evaluation
of patients with tuberous sclerosis every • Primary lymphoma of the kidney is extremely
2–3 years before puberty and yearly thereafter rare since the kidney has no lymphatic system.
to identify growing lesions. • Renal involvement is mainly due to hematog-
• Angiomyolipomas larger than 4 cm in diame- enous or direct spread of lymphoma from
ter should be treated with partial nephrectomy adjacent lymph nodes.
or selective catheter embolization to prevent • The proposed pathogenetic mechanismsof
potentially life-threatening hemorrhage. renal lymphomas include:
• In tuberous sclerosis, typically many angio- – Origin in the subcapsular lymphatics
myolipomas affect each kidney and it is vital – Seeding via hematogenous route
– Extension from retro peritoneal disease or • Malbrain proposed several criteria to diagnose
inflammatory disease with a lymphoplas- primary renal lymphoma as follows:
macytic infiltrate – Acute renal failure at the presentation in the
absence of other causes of renal impairment.
– Rapid improvement of renal function after
4.8.3 Diagnosis treatment
– Increased kidney size without any urinary
• Lymphoma commonly involves the kidney tract obstruction
secondarily from direct retroperitoneal exten- – Absence of other nodal involvement
sion or hematogenous metastases. beyond the kidney
• As many as 62 % of patients with lymphoma – A confirmed diagnosis made by biopsy
have renal involvement at autopsy, although • The most commonly encountered radiological
only 3 %–8 % of these patients demonstrate feature is that of multiple soft tissue masses,
renal involvement on abdominal CT-scan ranging from 1 to 3 cm, with minimal enhance-
(Figs. 4.88, 4.89, and 4.90). ment after contrast compared to surrounding
• Primary renal lymphoma is very rare. renal parenchyma.
• The presence of solitary renal lesion makes it
difficult to diagnosis as it resembles the more
common renal cell carcinoma (RCC).
Figs. 4.88, 4.89, and 4.90 Abdominal CT-scan showing bilateral renal lymphoma
4.8 Renal Lymphoma 161
• The differentiating features of renal lympho- that occasionally distort the renal contour
mas include: and displace the collecting system.
– Absence of calcification – They are usually homogeneous, are hypo
– Post contrast homogenous attenuation attenuating on nonenhanced and contrast-
– Absence of renal vein thrombus enhanced images, and may mimic multiple
– Absence of a mass effect on renal vessels renal cysts.
and pelvicalyceal system in PRL. – At US, they are hypoechoic
– However, this situation still demands a – Angiography shows hypovascular mass
biopsy to rule out RCC. lesions
• Other less commonly seen patterns in those – Diffuse infiltration of the kidney may result
with renal lymphomas include: in reniform enlargement.
– Enlarged non enhancing kidneys – Retroperitoneal disease occasionally
– Direct invasion of renal sinus and hilum by leads to vascular and ureteral
bulky retroperitoneal mass encasement.
– A diffuse perirenal infiltration encasing the – Perinephric involvement can arise from ret-
kidney roperitoneal disease or transcapsular spread
– Most of the patients also have adjacent ret- of parenchymal involvement.
roperitoneal adenopathy. – The CT findings of perinephric disease are
• MRI is currently becoming the imaging modal- variable and include small curvilinear areas
ity of choice for evaluation of renal lesions. of high attenuation, soft-tissue attenuation
– Lower signal intensity on unenhanced nodules, thickening of the Gerota fascia, or
T1-weighted images than normal renal cor- a mass contiguous with retroperitoneal
tex and less enhancement on early disease.
gadolinium-enhanced images differentiates
renal lymphoma from renal cell carcinoma.
• It is essential to differentiate between renal 4.8.4 Clinical Features
cell carcinoma and renal lymphoma in
patients presenting with solitary renal masses. • Lymphomas are malignant tumors that are
• Preoperative biopsy is worthwhile in patients caused by lymphoid cell proliferation.
with atypical radiological features, since it • Involvement of the kidney by lymphoma is a
may avoid nephrectomy. common late manifestation of advanced nodal
• The most common histological subtype disease.
encountered is diffuse large B cell lymphoma • Renal involvement in non-Hodgkin’s lym-
(DLBCL). phoma is usually seen as a part of dissemi-
• Lymphoma may also mimic nephroblastoma- nated disease.
tosis, however, lymphoma occurs typically in • PRL is a rare and uncertain entity because
older children and is associated with lymph- renal parenchyma lacks lymphatic tissue.
adenopathy elsewhere in the body. • The term primary renal lymphoma is used
• Imaging findings of renal lymphoma are vari- when the disease is localized to the kidney
able and include: without any sign of other organ involvement
– Solitary or multiple renal masses or or in which renal involvement is the present-
nodules ing manifestation.
– Diffuse infiltration • The reported incidence is as high as 47 % in
– Direct invasion from contiguous retroperi- autopsy series of lymphomas but clinically
toneal extension recognized in only up to 15 % of patients.
– Isolated perinephric disease • In children, non-Hodgkin lymphoma espe-
– The most common radiologic pattern is cially Burkitt lymphoma is more likely to
multiple parenchymal masses or nodules involve the kidney.
• Lymphomatous involvement of the kidney tumor metabolites may result in renal obstruc-
typically does not produce symptoms until tive or uric acid nephropathy.
late in the disease. • The treatment of non-Hodgkin’s Lymphoma
• Renal involvement is normally unilateral. (NHL) has been revolutionized with addition
• Bilateral involvement is unusual. of Rituximab to the standard chemotherapy.
• The clinical presentation is similar to the other This may overcome the poor outlook of this
renal malignancies. rare presentation of lymphoma.
• Flank or abdominal pain is the most frequent • PRL has a poor prognosis with rapid dissemi-
symptom. nation and a 75 % mortality rate 1 year after
• PRL can present with proteinuria or nephrotic diagnosis.
syndrome and rapidly progress to renal fail- • However, early diagnosis combined with che-
ure, especially when both kidneys are affected. motherapy + rituximab could improve sur-
• PRL has been associated with inflammatory vival rates.
and infectious chronic diseases, such as chronic
pyelonephritis, Sjögren’s syndrome, systemic
erythematous lupus, or Epstein-Barr virus.
• The clinical presentations of renal lymphomas 4.9 Ossifying Renal Tumor
include: of Infancy
– Flank or abdominal pain
– Hematuria • Ossifying renal tumor of infancy is a very rare
– Abdominal mass benign renal tumor.
– Fever • Ossifying renal tumor of infancy was first
– Weight loss described by Chatten in 1980 as a variant of
– Acute renal failure pediatric renal tumors.
– Hypertension is rare • It is an extremely rare, benign renal tumor
with classic clinical, radiological and histo-
pathological features.
4.8.5 Treatment and Prognosis • The Patients age at presentation ranges from
6 days to 14 months.
• The treatment of renal lymphoma depends on • Boys are more commonly affected than
the primary histological subtype. The addition girls.
of Rituximab to the standard CHOP chemo- • The left kidney is affected much more than the
therapy may improve the dismal outcome right (80 %).
reported so far. • The upper pole calices are the commonest site
• Diffuse Large B Cell Lymphoma (DLBCL) is involved.
the most common histology. • Etiology:
• A follicular lymphoma, small lymphocytic – The etiology of this tumor has not yet been
lymphoma or MALToma is not unusual. established.
• Patients with atypical features of renal cell – The origin and natural history of the lesion
carcinoma should undergo a preoperative per- are also uncertain.
cutaneous renal biopsy. – Some investigators believe that the ossifi-
• Nephrectomy can be avoided if a preoperative cation is the result of the osteogenic poten-
diagnosis is made. tial of urothelial cells.
• Systemic chemotherapy is currently the first – Others hypothesize that the spindle cells
treatment option for PRL. within the lesion resemble those seen in
• Treatment is mainly with chemotherapy; how- intralobar nephrogenic rests and that these
ever careful nephrological monitoring is lesions may lie within the pathologic
necessary during treatment since excretion of spectrum of Wilms tumor.
4.10 Metanephric Adenoma 163
• Gross features: • Treatment:

– The tumor is believed to arise from urothe- – The treatment is surgical excision.
lium and is attached to the renal medulla, – Open pyelostomy and tumor enucleation
specifically the papillary region of the renal – Partial nephrectomy
pyramids. • The biologic behavior of ossifying renal tumor
– From this location, it extends in a polypoid of infancy appears to be benign, with no
fashion into the collecting system. reported cases of malignant change or spread.
– It is seldom more than 2–3 cm in • Surgical excision is curative.
diameter.
• Microscopic features:
– At microscopic analysis, the lesion consists 4.10 Metanephric Adenoma
of three basic components:
• An osteoid core 4.10.1 Introduction
• Osteoblasts
• Spindle cells • Metanephric adenoma is also known as neph-
– Mature osteoid elements tend to be more rogenic adenofibroma or embryonal
prominent in older patients. adenoma.
• Clinical features: • Metanephric adenoma has been described in
– Hematuria is the usual presenting the past under other names such as néphrome
symptom. néphronogène, metanephroider Nierentumor
– This is intermittent painless gross and nephroblastomartiges Nierenadenom.
hematuria. • The term metanephric adenoma was sug-
– In infants with gross hematuria and a cal- gested by Brisigotti, Cozzutto et al. in 1992.
cified noninvasive mass in the pelvi-cal- • It is a benign renal tumor that can occur at any
ceal system, renal ossifying tumor should age.
be considered in the differential • It has been reported in patients as young as
diagnosis. 15 months and as old as 83 years (Mean age at
• Investigations: onset is around 40 years).
– MRI or CT scan offers a good diagnostic • It is more common in females.
guide. • It is usually unilateral, and no bilateral cases
– Abdominal ultrasound, CT-scan or MRI have been reported.
offers a good diagnostic guide. • The presenting features include abdominal
– On abdominal ultrasound, the mass is pain, hypertension, hematuria, a flank mass,
echogenic with shadowing, and hydrone- hypercalcemia, and polycythemia.
phrosis may be present. • Polycythemia is more frequent in MA than in
– Abdominal CT-scan shows a well-defined any other type of renal tumor.
mass, often calcified, with poor • The tumor is more commonly calcified than
enhancement. any other renal neoplasm
– At imaging, the renal outline is usually • Grossly, MA tumors appear tan in color with
maintained; however, filling defects with multiple foci of hemorrhage.
partial obstruction of the collecting system • MA is composed of tightly packed uniform
are often seen. small epithelial cells with small regular nuclei,
– Because of its location within the collect- a high nuclei-to-cytoplasm ratio, and no
ing system and its characteristic ossifica- mitotic figures.
tion, ossifying renal tumor of infancy may • At histologic analysis, there is proliferation of
mimic a staghorn calculus, which would be spindle-shaped mesenchymal cells encasing
exceedingly rare in the age group in which nodules of embryonal epithelium. Numerous
this lesion occurs. psammoma bodies may be seen.
• It is important to consider metanephric ade- 4.10.3 Diagnosis

noma in the differential diagnosis of pediatric
renal masses, since its benign nature allows • Metanephric adenoma (MA) is a rare, benign
local surgical resection with sparing of normal tumor of the kidney.
ipsilateral renal tissue. • Metanephric neoplasms comprise a spectrum
• It is different from mesonephric adenoma. of kidney tumors containing renal epithelial or
• Surgery is curative. stromal cells or both.
• Although metanephric adenoma (MA) is a
rare, benign neoplasm of epithelial cells, it is
4.10.2 Histopathology often difficult to distinguish this entity from
other malignant neoplasms preoperatively.
• Gross features: • The differential diagnosis of renal MA
– The mean size of the tumor is 5.5 cm with includes papillary renal cell carcinoma and
a range 0.3–15 cm. epithelial Wilms tumor.
– The tumors can be located at upper pole, • It is most important to distinguish MA from
lower pole or mid-hilar region of the papillary renal cell carcinoma.
kidney. • Currently, neither ultrasound nor CT scans
– These tumors are well circumscribed but can reveal distinct features of MA.
unencapsulated. • Ultrasound scans show a mass that is well
– On cut section, the tumor is tan pink, with defined and solid with both hyperechoic and
possible cystic and hemorrhagic foci. hypoechoic regions.
– Calcifications are uncommon, and only • Doppler evaluation shows the lesion to be
occur in approximately 20 % of cases. hypovascular.
• Microscopic features: • CT scans show a non-distinct mass with low
– Microscopically, metanephric adenoma attenuation on contrast studies, and small
can have an appearance similar to a nephro- calcifications may be present. The lesion
blastoma (Wilms tumours), or a papillary enhances less than normal renal
renal cell carcinoma. parenchyma.
– They show a uniform architecture of • Fine needle aspiration can be used as another
closely packed acinar or tubular structures less invasive method to diagnose MA, but it is
of mature and bland appearance with not as accurate as nephrectomy.
scanty interposed stroma. • Add to this the fact that cytological diagnosis
– The cells are small with dark staining using fine needle aspiration can be difficult.
nuclei and no nucleoli. • Despite being a benign lesion, MA should be
– Blastema is absent and glomeruloid figures routinely resected in order to confirm the
are a striking finding. diagnosis and rule out papillary renal cell
– The lumen of the acini may contain other- carcinoma.
wise epithelial infoldings or fibrillary
material but it is quite often empty.
– Mitoses are absent. 4.10.4 Clinical Features
– The tumor cells characteristically have
round nuclear membrane, no nucleoli, and • Metanephric adenoma (MA) is a rare neo-
fine chromatin. plasm, accounting for 0.2 % of adult renal epi-
• Metanephric adenoma lacks the frequent gain thelial neoplasms.
of chromosomes 7 and 17 and losses of the Y • Metanephric adenoma can occur at any age.
chromosome that are seen in patients with • It has been reported in patients as young as
papillary renal cell carcinomas. 15 months and as old as 83 years.
4.11 Multilocular Cystic Renal Tumor 165
• The majority of cases occurs in patients – They recommended that the term cystic
50–60 years of age and is seen predominantly nephroma be used to describe a multicystic
in females by a 2:1 ratio. tumor lacking blastemal or other embryo-
• MA is a rare neoplasm that often presents as nal elements.
an asymptomatic renal mass. – They suggested that the term cystic par-
• The clinical presentation include: tially differentiated nephroblastoma
– Abdominal pain (CPDN) be used to denote a predominantly
– Abdominal mass cystic lesion without nodular solid regions
– Hematuria and in which the septa contain blastemal or
– Dysuria other embryonal elements.
– Fever – Furthermore, they proposed that both terms
– Hypertension be used as subsets of the category term
– Hypercalcemia multilocular cystic renal tumor.
– Polycythemia • Multilocular cystic renal tumor has a bimodal
• Among renal tumors, MA has the highest inci- age and sex distribution and tends to occur in
dence (12 %) of polycythemia. children (mostly boys) between 3 months and
• Several tumors can resemble MA including 4 years of age and in adults (mostly women)
Wilms tumor, metastatic lung carcinoma, and between 40 and 60 years of age.
metastatic papillary thyroid carcinoma; how- • Multilocular cystic renal tumor are usually
ever, it is most difficult to distinguish MA solitary, but bilateral tumors have been
from papillary renal cell carcinoma. described.
• Multilocular cystic renal tumor most fre-
quently manifests in children as a painless
4.10.5 Treatment abdominal mass or less commonly as hematu-
ria and urinary tract infection.
• Metanephric adenomas are benign tumors and • The differential diagnosis of a pediatric multi-
because of this some advocate no treatment is locular renal mass includes cystic nephroma,
needed. cystic Wilms tumor or renal cell carcinoma,
• Although MA is usually benign, there are a clear cell sarcoma, cystic variants of meso-
few reported cases of metastatic disease. blastic nephroma, and multicystic dysplastic
• Surgical resection is important in order to con- kidney.
firm the diagnosis and rule out papillary renal • Multilocular cystic renal tumor is a term that
cell carcinoma. encompasses two histologically distinct but
• Surgery is curative and no other treatment is grossly indistinguishable renal tumors:
recommended. – Cystic nephroma
– Cystic partially differentiated nephroblas-
toma (CPDN)
4.11 Multilocular Cystic Renal • A cystic nephroma is a rare benign renal tumor
Tumor that is also known as:
– Multilocular cystic nephroma
• In 1956, Boggs and Kimmelstiel first pro- – Mixed epithelial stromal tumor (MEST)
posed the true neoplastic nature of these – Renal epithelial stromal tumor (REST)
lesions, suggesting the term benign multilocu- • Cystic nephroma is a purely multiloculated
lar cystic nephroma. cystic mass characterized by multiple septa-
• Joshi and Beckwith proposed a modification tions composed entirely of differentiated tis-
to the existing terminology. sues, without blastemal elements.
– Their modification emphasized a neoplas- • CPDN is also a multiloculated cystic mass
tic rather than a developmental or hamarto- without nodular solid components, but its
matous origin. septa contain embryonal cells.
• Multilocular cystic renal tumors primarily – The histopathologic characteristics of cys-

affect boys during early childhood, with a sub- tic nephromas are striking.
stantial number of the lesions containing blas- • The gross specimen shows a cluster of
tema (CPDN), and adult women, with lesions noncommunicating cysts of varying
that more commonly lack septal blastema sizes.
(cystic nephroma). • The cysts size ranges from several mil-
• As a rule, nephrectomy is curative and the limeters to 4 cm in diameter.
clinical course is benign, but CPDN may recur • The cysts are well circumscribed by a
locally. thick outer pseudocapsule that com-
• Cystic nephroma and CPDN cannot be distin- presses the adjacent normal renal
guished radiologically. parenchyma.
• The differential diagnosis includes other pedi- • The lesion is usually 5–10 cm in diam-
atric cystic renal tumors: eter and may extend beyond the normal
– Wilms tumor with cyst formation due to reniform configuration into the renal
hemorrhage and necrosis pelvis and the perinephric spaces.
– Cystic clear cell sarcoma • The cysts are lined with flattened, cuboi-
– Cystic mesoblastic nephroma dal, or hobnail-appearing cells and to
– Cystic renal cell carcinoma contain straw-yellow, proteinaceous,
– Multicystic dysplastic kidney colloid-like fluid.
– Segmental multicystic dysplasia in a dupli- • The intervening septations conform to
cated renal collecting system the cyst contours and do not form nodu-
• A cystic nephroma: lar masses.
– This is a benign cystic lesion of the kidney – In a review of the literature, Joshi and
of unknown etiology. Beckwith outlined the revised criteria for
– The first cystic nephroma was described by the diagnosis of cystic nephroma:
Edmunds in 1892 but it was called “cystic • The lesion is composed entirely of cysts
adenoma of the kidney.” and their septa.
– Subsequently, it was called “multilocular • The lesion forms a discrete mass, well
cyst of the kidney”. demarcated from the noncystic renal
– Cystic nephromas usually occur before age parenchyma.
2 and after age 40. • The septa are the only solid portions of
– Cystic nephroma has not been described the tumor, conforming to the outlines
either in the antenatal or neonatal periods, without solid expansile nodules.
which should help to differentiate it from • The cysts are lined by flattened, cuboi-
other tumors such as cystic mesoblastic dal, or hobnail-appearing epithelium.
nephroma. • The septa are composed of fibrous tis-
– They are not commonly found in adoles- sue in which well-differentiated tubules
cents and young adults. may be present but poorly differentiated
– In children, cystic nephromas are more tissues and blastemic cells are absent.
commonly found in boys and in adults, it is – It is generally believed that well-
more commonly found in females. differentiated, mature renal tubules and
– Bilateral cases are exceedingly rare. mature heterologous tissues, such as skele-
– The most common presenting symptoms tal muscle and cartilage, may be found in
and signs are: cystic nephromas but that hemorrhage and
• Flank mass necrosis are not observed.
• Flank or abdominal pain – There is controversy as to whether calcifi-
• Urinary tract infection cation may be found in cystic nephromas.
• Hematuria
4.11 Multilocular Cystic Renal Tumor 167
– Radiologically, abdominal ultrasound, – A well-circumscribed, encapsulated multi-

MRI and CT-scan are useful but a definitive cystic mass with variably enhancing septa
diagnosis and exclusion of an associated and no excretion of contrast agent into the
malignancy cannot be ensured. This is even loculi.
in spite of the addition of percutaneous – The septae are of uniform thickness and
biopsies. only minimally hyperemic on color
– The presence of solid components should Doppler ultrasound.
discourage a diagnosis of cystic nephroma. – The contents of the cyst may have similar
– The treatment of choice for cystic nephroma or slightly higher attenuation than that of
is surgical extirpation. water, and if the cystic spaces are very
– Nephron-sparing surgery should be consid- small, the closely packed septa can mimic a
ered also. solid mass.
– Cystic nephromas are benign, and the pos- – On CT images, visualizing the symmet-
sibility of a recurrence developing after ric excretion of contrast material by the
complete surgical extirpation of the neo- remaining functioning renal parenchyma
plasm is unlikely. helps to differentiate MCRT from multi-
• Multilocular cystic renal tumor encompasses cystic dysplastic kidney. However, it
a spectrum ranging from a purely cystic lesion may be difficult to differentiate segmen-
lined by epithelium and fibrous septa with tal multicystic dysplastic kidney from
mature tubules (cystic nephroma) to a lesion cystic nephroma on the basis of imaging
in which the septa contain foci of blastemal alone.
cells (cystic partially differentiated • Cystic nephroma and CPDN are indistinguish-
nephroblastoma). able from one another based on their gross and
• Cystic partially differentiated nephroblastoma radiographic appearances.
is distinguished from cystic Wilms tumor by • Gross features:
the absence of expansile solid masses of – MCRT is a well-circumscribed mass with a
nephroblastomatous tissue. thick fibrous capsule that contains multi-
• Cystic nephroma and cystic partially differen- ple, fluid-filled, noncommunicating loculi
tiated nephroblastoma are uncommon, benign separated by thin translucent septa.
lesions that cannot be differentiated by means – The loculi can range in size from micro-
of their gross or radiographic appearance. scopic to 4 cm in diameter.
• Multilocular cystic renal tumors tend to mani- • Microscopic features:
fest at two age peaks: – At microscopic examination, the septa are
– In children aged 3 months to 4 years (pre- lined by flattened or cuboidal epithelia,
dominantly boys with cystic partially dif- with areas of eosinophilic cuboidal cells
ferentiated nephroblastoma) protruding into the lumen that produce a
– In adults (pre-dominantly women with cys- hobnail or teardrop appearance.
tic nephroma) – Mature renal tubules may be seen within
• Patients frequently present with a painless the septa.
abdominal mass, and systemic symptoms are – Unlike CPDN, cystic nephroma does not
rare. Rarely, they present with hematuria or contain blastemal cells within the septa.
urinary tract infection. • Imaging studies demonstrate a well-
• Abdominal ultrasound and CT-scan findings circumscribed, encapsulated mass consisting
in those with multilocular cystic renal tumor of multiple cysts from several millimeters to
(MCRT) include: 4 cm in diameter, with variably enhancing
– Large multilocular renal cystic mass some- septa and no excretion of contrast material
times extending into the renal hilum. into the loculi.
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Not CXR in patients treated for favorable histology
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Multi Cystic Dysplastic Kidney
(MCDK) 5
5.1 Introduction • Those with bilateral disease often have other

severe malformation syndromes.
• Multicystic dysplastic kidney (MCDK), a • In bilateral cases, the newborn has the classic
variant of renal dysplasia results from the mal- characteristic of Potter’s syndrome.
formation of the kidney during fetal • Bilateral multicystic dysplastic kidney is
development. incompatible with survival.
• Other terms used to describe this condition • In those with unilateral multicystic dysplastic
include multicystic kidney and multicystic kidney:
renal dysplasia. – Contralateral ureteropelvic junction
• Renal dysplasia results from an abnormal obstruction is found in 3–12 % of infants.
metanephric differentiation. – Contralateral vesicoureteral reflux is seen
• Renal dysplasia is the leading cause of end- in 18–43 % of infants.
stage renal disease in children. – A voiding cystourethrography should be
• It consists of a spectrum of renal conditions, part of the work up of these patients.
including: • The incidence of unilateral multicystic dysplas-
– Renal hypoplasia tic kidney is reported to be 1 in 4,300 live births.
– Multicystic dysplastic kidney • The combined incidence of unilateral and
– Renal aplasia bilateral multicystic dysplastic kidney is 1 in
• Multicystic dysplastic kidney is characterized 3,600 live births.
by the presence of multiple, noncommunicat- • Bilateral multicystic dysplastic kidney occurs
ing cysts of varying size separated by dysplas- in about 20 % of prenatally diagnosed cases of
tic parenchyma and the absence of a normal multicystic dysplastic kidney.
pelvicaliceal system (Fig. 5.1). • Unilateral multicystic dysplastic kidney is
• The condition is associated with ureteral or more common in males with a male-to-female
ureteropelvic atresia, and the affected kidney ratio of 1.48:1.
is nonfunctional. • The left kidney is involved in 55 % of cases,
• Multicystic dysplastic kidney is the most com- and the right kidney is involved in 45 %.
mon cause of an abdominal mass in the • Diagnosed multicystic dysplastic kidney and
newborn period and is the most common cys- on follow-up:
tic malformation of the kidney in infancy. – May persist without any change
• Multicystic dysplastic kidney can be unilateral – May increase in size
or bilateral. – May undergo spontaneous involution

174 5 Multi Cystic Dysplastic Kidney (MCDK)
• During its caudal migration, the nephric duct

induces three embryonic kidneys in the neph-
rogenic cord:
– The pronephros
– The mesonephros
– The metanephros
• Normal renal development is dependent upon
the interaction of the metanephric bud and the
metanephric blastema.
• The nephric duct gives rise to a caudal diver-
ticulum called the ureteric bud.
• This invades the metanephric mesenchyme
which becomes the ultimate kidney.
• The interactions between the metanephric
mesenchyme and the ureteric bud leads to the
Fig. 5.1 A clinical photograph showing multicystic dys- development of the future kidney.
plastic kidney showing multiple noncommunicating cysts • This interaction results in the formation of
of varying sizes. These cysts are separated by dysplastic
renal parenchyma and absence of pelvicaliceal system calyces, tubules and nephrons.
• Complete obstruction or atresia impairs ure-
teral branching and results in decreased divi-
sion of collecting tubules and inhibition of
• Most cases of unilateral multicystic dys- induction and maturation of nephrons.
plastic kidney undergo spontaneous • The collecting tubules enlarge and develop
involution. cysts in their terminal portions.
• Calcification may develop in persistent multi- • These cysts of various sizes are distributed
cystic dysplastic kidney. randomly throughout the abnormal kidney
• Multicystic dysplastic kidney is usually and are held together by connective tissue,
asymptomatic but can be complicated by: without macroscopic evidence of intercom-
– Urinary tract infection (UTI) munication of cysts.
– Hypertension • In muticystic renal dysplasia the renal pelvis
– Neoplasia and or ureter are usually atretic.
• In this and other forms of dysplasia, the more
proximal the level of obstruction, the more
5.2 Embryology likely the cysts will be large.
• It has been hypothesized by Pathak et al.
• The urogenital system is predominantly that these changes are the result of the pres-
derived from the intermediate mesoderm of sure effects on the kidney from the
the embryo. obstruction.
• This intermediate mesoderm undergoes epi- – Proximal obstruction results in calyces that
thelial transformation to form the nephric are markedly distended with cyst
duct. formation.
• The nephric duct extends adjacent to another – In those with distal obstruction as in poste-
tract called the nephrogenic cord which is also rior urethral valves, the pressure effects are
derived from mesoderm. more generalized and less severe, so that
• The nephric duct induces the adjacent nephro- the calyces do not distend as much. The
genic cord mesenchyme to aggregate and kidneys will become dysplastic with much
transform into epithelial tubules. smaller and less visible cysts.
5.4 Histologic Findings 175
• During embryonic development the central • Teratogens may also play a role in abnormal
elements of the kidney form first and the more renal development. Although, their associa-
peripheral elements form later. tion with multicystic dysplastic kidney has not
• The metanephric mesenchyme forms the been clearly established.
proximal components of the nephron from the
glomerulus to the distal convoluted tubule.
• The ureteric bud that invades and branches 5.3 Etiology
inside the mesenchyme forms the distal com- and Pathophysiology
ponents of the nephron, including the collect-
ing ducts, calyces, pelvis, and ureter. • The exact etiology of multicystic dysplastic
• The ureteric bud theory: kidney is not known.
– This was proposed by Mackie and Stephens • Genetic factors are important etiological fac-
– Multicystic dysplastic kidney results from tors for multicystic dysplastic kidney.
an abnormal induction of the metanephric • Multicystic dysplastic kidney result from an
mesenchyme by the ureteral bud. abnormal induction of metanephric
– This abnormal induction might be due to: mesenchyme.
• A defect in the formation of the meso- – Some mutations in genes associated with
nephric duct renal dysplasia (in syndromes) have been
• Malformation of the ureteric bud determined.
• Degeneration of the ureteric bud at an – These mutations occur at EYA1 or SIX1
early stage. genes (branchio-oto-renal syndrome).
– The final shape of the dysplastic kidney – The PAX2 gene is also thought to play a
depends on the timing of the defect to the role in the etiology of multicystic dysplas-
ureteric bud and on the effect of this on the tic kidney.
ureteric bud branching. • Multicystic dysplastic kidney can be a conse-
• Multicystic dysplastic kidney usually devel- quence of a genetic syndrome, which in turn
ops as a sporadic problem; although, familial may affect the digestive tract, nervous system,
cases have been reported. or other areas of the urinary tract.
• Mutations in genes important in ureteric bud • Medications such as antihypertensives taken
development have been identified in syn- by the mother during pregnancy may play a
dromes with renal dysplasia, including multi- role in the pathogenesis of multicystic dys-
cystic dysplastic kidney. These include: plastic kidney.
– Mutations in EYA1 or SIX1 genes that
lead to branchio-oto-renal (BOR)
syndrome. 5.4 Histologic Findings
– Mutations in the PAX2 gene, the cause of
Renal-coloboma syndrome (RCS), are • Gross findings (Figs. 5.2, 5.3, 5.4, 5.3, 5.6,
associated with renal dysplasia. and 5.7):
– Hereditary MCDK was found in three gen- – The multicystic dysplastic kidney is enlarged,
erations of a family that also carried a abnormally shaped, and often resembles a
PAX2 gene mutation. bunch of grapes (Figs. 5.2 and 5.3).
– PAX2 mutations have also been identified – The kidney is composed of numerous and
in patients with isolated renal hypoplasia/ irregularly sized cysts.
dysplasia. – The cysts range in size from less than 1 mm
• Exposure to viral infections in utero has been to several centimeters in diameter.
associated with multicystic dysplastic kidney. – The number of cysts is also variable rang-
These include cytomegalovirus (CMV), ing from <5 cysts in 34 % of patients to >5
enterovirus, and adenovirus. cysts in 66 % of patients.
Figs. 5.2 and 5.3 Clinical photographs showing multicystic dysplastic kidney. Note the kidney which is composed of
multiple noncommunicating cyst of varying sized that resembles a bunch of grapes
DUPLEX
SYSTEM
DYSPLASTIC
DILATED KIDNEY
URETER
DYSPLASTIC
KIDNEY
Figs. 5.4 and 5.5

Intraoperative photographs
showing small, dysplastic
involuted kidneys. Note the
duplex system on the right
side
5.4 Histologic Findings 177
Figs. 5.6 and 5.7 Clinical

photographs showing DYSPLASTIC
DYSPLASTIC KIDNEY
dysplastic kidneys in kidneys KIDNEY
with duplex systems
DUPLEX
SYSTEM
DUPLEX
SYSTEM
– The cysts contain a clear or yellow fluid – The change in size of the cysts in multi-
and are connected by a fibrous tissue cystic renal dysplasia are likely related to
stroma. the number of preserved glomeruli and
– Cysts may be quite large, as in the classic thus the degree of residual renal function
description of multicystic dysplastic kid- (Fig. 5.11).
ney, or the kidney may be echogenic and – As long as the kidney is able to filter
dysplastic or small and involuted. plasma, the overall size of the multicystic
– It has been suggested that some cases of dysplastic kidney will increase.
renal agenesis may be due to involuted – As the nephrons become fibrotic, the
cases of multicystic kidney disease. amount of filtrate will diminish and the
– There is loss of kidney and pelvocaliceal growth of the kidney will stop and subse-
differentiation. quently decrease in size.
– Rudimentary renal tissue or lobes are – On follow-ups of multicystic dysplastic
sometimes grossly identifiable. kidneys, it was shown that:
– Sometimes, multicystic dysplastic kid- • 70 % decrease in size
ney might be seen in only the upper or • 20 % showed no change in size
lower pole of a duplicated collecting • 10 % increased in size
system. • Microscopic findings:
– Ureteral or ureteropelvic atresia is always – Histopathologic examination reveals abnor-
present (Figs. 5.8, 5.9, and 5.10). mal ductal differentiation and only rudi-
– The atretic portion of the ureter varies in mentary corticomedullary differentiation.
length from 1 to 5 cm. – Thick-walled or thin-walled cysts with
– The ipsilateral renal artery is absent or smooth inner linings are present through-
hypoplastic. out the kidney.
ATRETIC URETER
ATRETIC URETER
ATRETIC URETER
Figs. 5.8, 5.9, and 5.10 Clinical photographs showing multicystic dysplastic kidneys. Note the atretic ureters
sent the principal microscopic criteria for a

diagnosis of multicystic dysplastic kidney.
– Although the kidney in multicystic dyspla-
sia is usually described as having no renal
function, there is evidence that these kid-
neys may have some component of residual
renal function.
– Microscopic examination of the MCDK
has shown that the number of nephrons are
reduced but are seldom absent.
– The glomeruli are primitive, and some-
times normal glomeruli may be seen.
Fig. 5.11 Clinical intraoperative photograph showing
multicystic dysplastic kidney showing multiple cysts of
different sizes
5.5 The Natural History

– Normal renal parenchyma is usually of Multicystic Dysplastic
absent. Kidney
– The loose connective tissue that surrounds
the cysts might range from thin strands to • Multicystic dysplastic kidney can be diag-
extensive areas of fibrosis. nosed prenatally.
– Primitive epithelial ducts and nests of • Some cases of prenatally diagnosed multicys-
metaplastic cartilage are seen. These repre- tic dysplastic kidney monitored prior to birth
5.6 Classification 179
demonstrate an initial increase in size fol- • Typically, MCDK is a unilateral disorder and
lowed by involution. bilateral MCDK is incompatible with life.
• An involution of prenatally diagnosed multi- • Several forms of MCDK have been described.
cystic dysplastic kidney has been noted before – The classic type
birth. – The less common hydronephrotic type
• The natural history of multicystic dysplastic – A third type known as solid cystic
kidney is variable: dysplasia
– They may persist without any change • The classic type has a random configuration of
– They may increase in size cysts, whereas the hydronephrotic type pres-
– They may undergo spontaneous involution ents with a discernible, dilated renal pelvis
– Most cases of unilateral multicystic dys- surrounded by cysts.
plastic kidney undergo spontaneous • The solid cystic dysplasia is composed of
involution smaller cysts with a greater amount of non-
• Calcification may develop in persistent multi- functional parenchyma.
cystic dysplastic kidney. • MCDK should not be confused with polycys-
• The Multicystic Kidney Registry reported 260 tic kidney disease (PCKD) or other renal cys-
patients with multicystic dysplastic kidney tic diseases.
whose cases were managed nonoperatively • The multicystic kidney is a dysplastic kidney
and whose cases were followed for varying which has been classified by Potter et al. as
periods as long as 5 years. type II disease.
– Approximately 18 % of these kidneys were • Subsequently, this type has been sub classified
undetectable by age 1 year. into two groups:
– 31 % were undetectable by age 3 years – Type IIa
– 54 % were undetectable by age 5 years. – Type IIb
– The more common type IIa is secondary to
pelvoinfundibular atresia.
5.6 Classification – Type IIb is the hydronephrotic form.
– The pelvoinfundibular atresia and resulting
• Multicystic dysplastic kidney (MCDK) was dysplasia of MCKD is thought to result
first described as a distinct clinical entity by from a vascular insult.
Spence in 1955. – MCKD have been reported to be familial in
• In 1986, the Urology Section of the American few cases.
Academy of Pediatrics established the – Ipsilateral multicystic dysplastic kidney
National Multicystic Kidney Registry, which was also reported in identical twins.
is a large, multicenter, longitudinal database
that has helped clarify the appropriate man- Potter classification of renal dysplasia
agement of MCDK. Type I Autosomal recessive polycystic kidney
disease (ARPKD)
• Multicystic dysplastic kidney (MCDK) is a
Type IIa Multicystic dysplastic kidney disease
congenital maldevelopment of the kidney in [pelvo-infundibular atresia] (MDKD)
which the renal cortex is replaced by numer- Type IIb Multicystic dysplastic kidney disease
ous cysts of multiple sizes. [hydronephrotic type] (MDKD)
• A dysplastic parenchyma anchors the cysts, Type III Autosomal dominant polycystic kidney
the arrangement of which resembles a bunch disease (ADPKD)
of grapes. Type IV Cystic dysplasia due to urethral obstruction
• No functional renal tissue can be identified.
• The calyceal drainage system of the affected
kidney is absent.
5.7 Associated Anomalies – 49,XXXXX syndrome (hypertelorism, epi-

canthic folds, microcephaly, short neck,
• Multicystic dyplastic kidney is associated clinodactyly of the fifth finger, small hands
with contralateral renal disease in a significant and feet, and mental retardation).
number of patients. – Alagille syndrome (liver disease, cardiac
• Previous reports have shown that MCDK is defects, characteristic facies, renal anoma-
associated with a 20–45 % incidence of con- lies, vascular anomalies and anomalies of
tralateral renal anomalies. the eye, pancreas, and skeletal system. The
• The most common contralateral abnormality condition is associated with mutations in
was vesicoureteral reflux and ureteropelvic the JAG1 gene that encodes for a ligand of
junction obstruction. Notch.
• Bilateral MCDK was reported in 19 % and – Beckwith-Wiedemann syndrome (macro-
contralateral renal agenesis in 11 %. somia, microcephaly, macroglossia, vis-
• Contralateral hydronephrosis was seen in 7 %. ceromegaly, omphalocele, and
• 30–35 % of fetuses with MCDK have associ- hypoglycemia).
ated non-renal abnormalities. – Branchio-oto-renal (BOR) syndrome
• The most common abnormalities were those (hearing loss, ear malformations, branchial
of the heart, followed by the spine, extremi- cleft fistulas or cysts, and renal dysplasia or
ties, face and umbilical cord. renal agenesis. The BOR syndrome is an
• Fetuses with bilateral MCDK are more likely autosomal dominant condition caused by
to have associated non-renal abnormalities mutations in the EYA1 and SIX1 genes.
(66.7 %) in comparison with fetuses with uni- – Hypoparathyroidism-deafness-renal syn-
lateral MCDK (25.6 %). drome (sensorineural deafness, hypopara-
• Abnormal chromosomes: thyroidism, and urinary tract anomalies,
– Abnormal chromosomes (10 %). including renal dysplasia). This autosomal
– Female fetuses (20 %) are more likely to dominant syndrome is caused by mutations
have an abnormal chromosome study than in the GATA3 transcription factor.
male fetuses (5.6 %). – Joubert syndrome (hypoplasia of the cere-
– Fetuses with bilateral MCDK disease bellar vermis, hypotonia, and impaired
(16.7 %) are more likely to have an abnor- psychomotor development together with
mal karyotype than fetuses with unilateral abnormal respiratory pattern, abnormal eye
MCDK (7.7 %). movements with poor vision, or both). This
– No karyotype abnormalities were found in syndrome is an autosomal recessive
fetuses with unilateral MCDK if an associ- condition.
ated non-renal abnormality was not found. – Maturity-onset diabetes of the young type
• The ratio of male to female fetuses was 2.4:1. V (MODY5): MODY5 is a monogenic
• Female fetuses were twice as likely to have form of diabetes with an autosomal domi-
bilateral MCDK as males. nant mode of inheritance caused by muta-
• Vesicoureteic reflux in the contralateral kid- tions in the hepatocyte nuclear factor 1-beta
ney (23 %). mutations. Patients present with diabetes,
• As most patients with multicystic dysplastic usually when younger than 25 years, with a
kidneys have pelvo-ureteral atresia on the wide spectrum of renal anomalies, includ-
affected side, it is unlikely that infected urine ing cystic dysplasia.
will reflux into the kidney. – Renal coloboma syndrome (RCS): The
• Multicystic dysplastic kidney has been RCS is an autosomal dominant condition
reported in various syndromes, including the caused by mutations in the transcription
following: factor PAX2 and characterized by optic
5.7 Associated Anomalies 181
nerve coloboma and renal malformations, • Patent ductus arteriosus

including dysplasia. • Pulmonary stenosis
– Trisomy 18: Patients with trisomy 18 have • Truncus arteriosus
a prominent occiput, micrognathia, low-set • Ventricular septal defect
ears, and flexion deformities of the fingers, – Musculoskeletal
congenital heart disease, and mental • Clinodactyly of the fifth finger
retardation. • Congenital dislocation of the hip
– VACTERL association: The VACTERL • Flexion deformities of the fingers
association refers to the combination of • Syndactyly
vertebral defects (V), anal atresia (A), car- • Talipes equinovarus
diovascular anomalies (C), tracheoesopha- – Miscellaneous
geal fistula (TE), renal anomalies (R), and • Bipartite uterus
limb defects (L). In 20 % of these patients, • Cleft palate
cystic renal disease may be found. • Epicanthic folds
– Waardenburg syndrome type 1: Patients • Hymenal atresia
present with developmental anomalies of • Hypertelorism
the eyelids, eyebrows, and nose root; pig- • Low-set ears
mentary defects of the iris and hair; and • Macroglossia
congenital deafness. • Macrosomia
– Williams’ syndrome: This syndrome is • Micrognathia
characterized by elfin facies, mental retar- • Pigmentary defects of iris and hair
dation, supravalvular aortic stenosis, and • Preauricular pit
neonatal hypercalcemia. • Short neck
• Nonrenal malformations reported in patients • Urinary malformations associated with multi-
with multicystic dysplastic kidney include the cystic dysplastic kidney include the
following: following:
– Gastrointestinal malformations: – Bladder wall diverticulum
• Duodenal atresia – Contralateral renal agenesis
• Esophageal atresia – Dysplasia
• Hirschsprung’s disease – Hypoplasia
• Anorectal malformations – Crossed fused renal ectopia
• Inguinal hernia – Cystic dysplasia of the testis
• Omphalocele – Ectopic kidney
• Tracheoesophageal fistula – Fibromuscular dysplasia
– Neurologic malformations – Horseshoe kidney
• Anencephaly – Patent urachus
• Caudal agenesis – Seminal vesicle abnormalities
• Caudal regression syndrome – Ureterocele
• Congenital deafness – Contralateral ureteropelvic junction
• Hydrocephalus obstruction has been reported in 7–12 % of
• Mental retardation patients.
• Microcephaly – Posterior urethral valves
• Microphthalmia – Contralateral vesicoureteral reflux is
• Myelomeningocele reported in 4–19 % of patients.
• Spina bifida • In children older than 2 years, 72 % of patients
– Cardiovascular malformations with multicystic dysplastic kidney showed
• Aortic stenosis compensatory growth of the contralateral
• Coarctation of the aorta kidney.
5.8 Clinical Features those with enlarged MCDK. Rarely, ring like
calcifications of the cyst walls may be seen on
• Most cases of multicystic dysplasia of the kid- plain radiographs.
ney (MCDK) are detected during fetal ultraso- • Abdominal ultrasound is the preferred initial
nography and are reported as early as examination.
15 weeks’ gestation. – Ultrasonography is an excellent diagnostic
• An abdominal mass in the flank of an other- test for MCDK, with a high degree of
wise healthy newborn was the most common confidence.
clinical presentation of unilateral multicystic – Currently, the majority of MCDK cases are
dysplastic kidney. diagnosed by antenatal ultrasound
• The abnormal kidney is palpable in only examination.
13–22 % of patients. – Abdominal ultrasound is accurate, and it
• The mass is usually mobile, ballotable, and does not require sedation, radiation, and
irregular in shape, nontender, and might can be repeated easily.
transilluminate. – The cysts of MCDK may become enlarged,
• Multicystic dysplastic kidney is usually may shrink, or may involute during fetal
asymptomatic and can remain undetected into life.
adulthood. – Bilateral MCDK may occur with oligohy-
• Abdominal or flank pain and respiratory dis- dramnios as a result of poor urine
tress are uncommon symptoms because of the production.
pressure effect of the abnormal kidney. – In patients with a prenatal diagnosis of
• Multicystic dysplastic kidney might be dis- MCDK, a postnatal ultrasound should be
covered during an investigation for urinary done prior to discharge to differentiate
tract infection (UTI), voiding dysfunction, or MCDK from hydronephrosis.
hypertension. Multicystic dysplastic kidney – Abdominal ultrasounds characteristically
may also be discovered when diagnostic imag- show:
ing studies are performed to investigate a non- • Hypoechoic cysts of variable sizes and
urinary problem. shapes
• Bilateral multicystic dysplastic kidney usually • Interfaces between cysts
results in stillbirth or death within the first few • A nonmedial location of large cysts
days of life; however, an infant with bilateral • The absence of an identifiable renal
multicystic dysplastic kidney who survived sinus
for 17 days was reported. • Lack of communication between cysts
• Bilateral multicystic dysplastic kidney is usually • Minimal surrounding parenchyma
associated with oligohydramnios, amnion nodo- – An obstructive uropathy with little renal
sum, pulmonary hypoplasia, and Potter facies. parenchyma can mimic MCDK, but radio-
• Infants with bilateral multicystic dysplastic nuclide studies can provide confirmation of
kidney who survive have renal failure from the diagnosis.
birth and require dialysis from the first day of – The presence of a kidney shape and/or a
life. large cystic structure in the medial portion
of the kidney on ultrasound evaluation are
more suggestive of hydronephrosis than
5.9 Investigations MCDK. In MCDK, the cysts do not com-
municate, while in hydronephrosis there is
• CBC communication with the central renal
• Serum electrolytes, BUN and creatinine pelvis.
• Urine analysis and culture – The autosomal recessive polycystic kidney
• Abdominal radiograph may show a soft tissue disease (PCKD) is not usually mistaken for
density with displacement of the bowels in MCDK, as the cysts in PCKD are too small
5.10 Treatment 183
to be visualized on sonograms, and the • Intravenous pyelography (IVP):

parenchyma is generally homogeneously – This is not usually necessary; however, if
hyperechoic. multicystic dysplastic kidney involves only
• Radionuclide scan: the upper or lower segment of a duplicated
– Radionuclide scan is useful in differentiat- system, an IVP might reveal a small but
ing an obstructed functioning kidney from functional ipsilateral kidney with an incom-
MCDK. plete and possibly dilated calyceal system.
– Radionuclide scan may be necessary if • Abdominal CT-scan is also rarely done to
ultrasonography does not reveal the classic diagnose MCDK (Figs. 5.12, 5.13, 5.14, 5.15,
features of multicystic dysplasia of the and 5.16).
kidney. – Abdominal CT-scan show the typical mul-
– Radionuclide scan is useful in estimating ticystic appearance of MCDK with little or
the function of the involved kidney. no parenchyma. Cyst wall calcification
– Technetium-99m (99mTc) mercaptoacetyl- may be seen also.
triglycine (MAG-3) and 99mTc dimercapto- – If a contrast-enhanced CT scan is per-
succinic acid (DMSA) studies can formed, there is no excretion seen.
demonstrate lack of function in the affected • Retrograde pyelography is rarely done to
kidney, but MAG-3 and DTPA studies can demonstrate an atretic or absent ureter. This is
also provide information regarding drain- usually done through a cystoscope.
age in an obstructed hydronephrotic – Retrograde pyelography demonstrates a
kidney. ureter that terminates blindly below the
– The hydronephrotic form of MCDK can ureteropelvic junction.
mimic ureteropelvic junction obstruction, • Abdominal MRI:
and radionuclide scanning is necessary to – This show the typical multicystic appear-
confirm the diagnosis. ance of MCDK with little or no
– On radionuclide scan, the area of the parenchyma.
MCDK appear as a photopenic region that
represents displaced tissue with back-
ground activity only. 5.10 Treatment
– DMSA renal scanning demonstrates
absence of function in the kidney with mul- • In the past, nephrectomy was often performed
ticystic dysplastic kidney. to establish the diagnosis.
• Voiding cystourethrography (VCUG): • Currently, the role of nephrectomy in multi-
– This is useful in patients with MCDK to cystic dysplasia of the kidney (MCDK) is
evaluate for vesicoureteral reflux (VUR). controversial.
– VUR could lead to reflux nephropathy in • The indications for nephrectomy in multicys-
the contralateral solitary kidney. tic dysplasia of the kidney are:
– Current recommendations for patients with – Large multicystic dysplastic kidney caus-
unilateral multicystic dysplastic kidney ing abdominal or flank pain
include evaluation of the contralateral kid- – Urinary tract infection (UTI)
ney for VUR by VCUG. – Hypertension
– VUR has been reported in 4–19 % of con- – Renal malignancy
tralateral kidneys but it is usually low grade • Multicystic dysplasia of the kidney can attain
and resolves in early life. a large size and cause significant abdominal or
– VCUG may be deferred, unless abnormal flank discomfort and pain and these should be
ultrasonography findings in the removed.
contralateral kidney or ureter and/or a his- • Urinary tract infection involving the multicys-
tory of UTI are noted. tic dysplastic kidney calls for its removal.
Figs. 5.12, 5.13, 5.14, 5.15, and 5.16 Multiple CT-scan showing multicystic dysplastic kidneys. Note the different
sizes of the cysts which are noncommunicating
• Multicystic dysplastic kidney complicated by affected by multicystic dysplastic kidney

hypertension is an indication for might provide a focus for malignant
nephrectomy. degeneration.
• The presence of a renal malignancy based on – No increased risk of Wilms tumor has been
diagnostic imaging is an indication for demonstrated in patients with multicystic
nephrectomy. dysplastic kidney.
– Some concern surrounds the possibility – Some authors recommend nephrectomy
that the intervening stroma of a kidney only in patients who do not show involution
Further Reading 185
over a defined period, such as the first 2. Atiyeh B, Husmann D, Baum M. Contralateral renal
abnormalities in multicystic-dysplastic kidney dis-
5 years of life.
ease. J Pediatr. 1992;121(1):65–7.
– The role of laparoscopic nephrectomy for 3. Baudoin P, Provoost AP, Molenaar JC. Renal function
multicystic dysplastic kidney is up to 50 years after unilateral nephrectomy in child-
controversial. hood. Am J Kidney Dis. 1993;21(6):603–11.
4. Beckwith JB. Should asymptomatic unilateral multi-
• It is recommended that children with multi-
cystic dysplastic kidneys be removed because of the
cystic dysplastic kidney should undergo renal future risk of neoplasia? Pediatr Nephrol.
ultrasonography every 6–12 months until age 1992;6(6):511.
5 years or until involution is noted. 5. Belk RA, Thomas DF, Mueller RF, et al. A family
study and the natural history of prenatally detected
• Patients with multicystic dysplastic kidney
unilateral multicystic dysplastic kidney. J Urol.
and contralateral VUR should receive antibi- 2002;167(2 Pt 1):666–9.
otic prophylaxis during infancy and early 6. Calaway AC, Whittam B, Szymanski KM, Misseri R,
childhood. It has been estimated that: Kaefer M, Rink RC, et al. Multicystic dysplastic kid-
ney: is an initial voiding cystourethrogram necessary?
– Spontaneous resolution of VUR occurred
Can J Urol. 2014;21(5):7510–4.
in 89 % of patients with grades I and II 7. Colodny AH. The management of multicystic dys-
VUR plastic kidney in infancy. Urology.
– Spontaneous resolution of VUR occurred 1995;45(6):1084–5.
8. Dungan JS, Fernandez MT, Abbitt PL, et al.
in only 50 % of patients with grades III and
Multicystic dysplastic kidney: natural history of pre-
IV VUR. natally detected cases. Prenat Diagn.
• Abdominal ultrasounds are done during fol- 1990;10(3):175–82.
low ups to ensure the healthy kidney is func- 9. Kuwertz-Broeking E, Brinkmann OA, Von Lengerke
HJ, et al. Unilateral multicystic dysplastic kidney:
tioning properly and that the unhealthy kidney
experience in children. BJU Int. 2004;93(3):388–92.
is not causing adverse effects. 10. Narchi H. Risk of hypertension with multicystic kid-
• It has been recommended that patients with ney disease: a systematic review. Arch Dis Child.
multicystic dysplastic kidney should be fol- 2005;90(9):921–4.
11. Sarhan OM, Alghanbar M, Alsulaihim A, Alharbi B,
lowed-up lifelong whether or not involution
Alotay A, Nakshabandi Z. Multicystic dysplastic kid-
has occurred or a nephrectomy has been per- ney: impact of imaging modality selection on the ini-
formed. Long-term follow-up of patients with tial management and prognosis. J Pediatr Urol.
a single kidney revealed: 2014;10(4):645–9.
12. Saxen L, Sariola H. Early organogenesis of the kid-
– Hypertension in 27–47 % of patients
ney. Pediatr Nephrol. 1987;1(3):385–92.
– Proteinuria in 23–47 % of patients 13. Wacksman J, Phipps L. Report of the multicystic kid-
– Renal insufficiency in 3–13 % of patients ney registry: preliminary findings. J Urol.
1993;150(6):1870–2.
Further Reading
1. Al Naimi A, Baumüller JE, Spahn S, Bahlmann
F. Prenatal diagnosis of multicystic dysplastic kidney
disease in the second trimester screening. Prenat
Diagn. 2013;33:1–6.
Congenital Ureteral Anomalies
6
– A small orthotopic ureterocele

– A nonobstructed, nonrefluxing primary
Congenital Ureteral Anomalies
mega ureter
• Duplex (duplicated ureters) (Fig. 6.1)
• Ectopic ureter
• Ureterocele
6.1 Etiology
• Mega ureter
• Vesicoureteral reflux (VUR)
• The ureter develops around the fourth and
sixth week of gestation.
• The ureter develops from a ureteral bud, the
early precursor of the ureter, branches off
from the caudal portion of the Wolffian (meso-
nephric) duct.
• The ureter grows cranially and caudally.
• The cranial portion of the ureteral bud joins
with the metanephric blastema and begins to
induce nephron formation.
• The bud subsequently branches into the renal
pelvis and the calyces and induces nephron
formation.
• The caudal portion of the ureteral bud along
Fig. 6.1 A reconstruction picture showing duplex with the mesonephric duct are incorporated
ureters into the cloaca as it forms the bladder
trigone.
• Ureteral anomalies develops as a result of
alterations in:
• The outcome of ureteral anomalies chiefly – Ureteral bud number
depends on the presence or absence of obstruc- – Ureteral bud position
tion and/or infection, and associated renal – Time of ureteral development
injury. • Incomplete (partial) ureteral duplication, with
• In the absence of these, no treatment may be a single ureteral orifice and bifid proximal
necessary, especially in the case of: ureters:
– Isolated ureteral duplication anomalies – This results from early branching of a sin-
– Low-grade VUR gle ureteral bud

188 6 Congenital Ureteral Anomalies
• Complete ureteral duplication: 6.2 Clinical Features

– This results from an accessory ureteral bud.
– Complete duplication occurs when two • The clinical presentations of ureteral anoma-
separate ureteric buds arise from a single lies are variable and the majority are
Wolffian duct. asymptomatic.
– According to the Weigert-Meyer rule, the • There are no specific clinical signs associated
future lower pole ureter separates from with ureteral anomalies.
Wolffian duct earlier and thus migrates • The diagnosis is sometimes suspected on rou-
superiorly and laterally as the urogenital tine prenatal ultrasound.
sinus grows. • Some patients present with UTI, abdominal
– The result is complete duplication, with the mass or hematuria.
upper ureter usually protruding into the • Children with primary mega ureters may also
bladder more medially and inferiorly than present with cyclic abdominal pain/flank pain,
the lower ureter. or, less commonly, acute pain crisis.
• Ectopic termination of a single system or of • Patients may present with a cystic mass at the
the ureter of a duplex system is the result of urethral meatus representing a prolapsed
the high (cranial) origin of the ureteral bud ureterocele.
from the mesonephric duct. • In other patients, the diagnosis is incidental
• Ectopic ureter: after imaging studies for unrelated
– This results from delayed incorporation of symptomatology.
the ureteral bud into the bladder. • Ureteral anomalies may be discovered during
– The resulting position of the ureteral orifice the evaluation of a patient with:
is more caudal and medial or in more – Hypertension
severe cases it inserts into one of the – Proteinuria
Wolffian duct structures. – Renal insufficiency in rare cases of severe
• The ureters are paired muscular tubes that run bilateral anomalies
from the renal pelvis to the bladder. • Approximately 50 % of females with ectopic
• The ureters run through three natural areas of ureters present with constant urinary inconti-
narrowing: nence or vaginal discharge.
– The ureteropelvic junction • In males, incontinence is never due to an ecto-
– The crossing of the iliac vessels pic ureter because the ectopic ureter never
– The ureterovesical junction (UVJ) inserts distal to the external urethral
• The UVJ may be divided into three sections: sphincter.
– The terminal portion (juxta vesical ureter) • Rarely, an ectopic ureteral insertion may pres-
– The intramural portion ent with recurrent epididymitis in pepubertal
– The submucosal portion (under the bladder boys.
mucosa). • Post pubertal males with ectopic ureters most
• The function of the ureter is to effectively trans- commonly present with chronic prostatitis and
port the urinary bolus from the minor calyces to painful intercourse and ejaculation.
the urinary bladder at acceptably low pressures.
• The efficiency of this function depends on
adequate coaptation of the ureteral wall to 6.3 Investigations and Diagnosis
propel the urinary bolus.
• If the ureter fails to propagate the peristaltic • Urinalysis and urine culture are important in
wave, the static urine distends the upper uri- children presenting with unexplained fever.
nary tract and reduces luminal coaptation. • The diagnosis of UTI should prompt further
• Other factors that may affect ureteral transport radiological evaluation to identify urological
include urinary volume and bladder pressure. anomalies.
6.4 Duplex (Duplicated) System 189
• Renal and bladder ultrasound: • Cystoscopy, vaginoscopy, and retrograde

– This is a first-line imaging study to evalu- pyelogram are endoscopic procedures that
ate the upper and lower urinary tract. allow direct visualization of the genital and
– Ultrasound evaluation of upper urinary tract lower urinary tracts and may include radio-
anomalies include ureteral duplication, dil- graphic visualization of the upper urinary tract
atation of collecting system, character and (e.g. retrograde pyelogram).
thickness of the renal parenchyma. • Pressure-perfusion studies (Whitaker test):
– Ultrasound evaluation of lower urinary – This measure differential pressures of the
tract anomalies include bladder wall thick- renal pelvis and the bladder
ness, ureterocele, bladder diverticulum, – It may be useful in evaluating equivocal
posterior urethral dilatation, and degree of urinary tract obstruction
bladder emptying. – It is invasive and depends on percutaneous
• Voiding cystourethrogram (VCUG): placement of a catheter
– This is valuable for evaluation of the blad- – It is seldom used in the modern era of
der and urethra. nuclear renography
– This includes evaluation of:
• VUR
• Bladder diverticulum 6.4 Duplex (Duplicated) System
• Ureterocele
• Bladder trabeculations and bladder 6.4.1 Introduction
emptying
• Urethral anatomy during voiding • A duplex collecting system is one of the most
• The ureters if VUR is present common congenital urinary tract
• Diuretic nuclear renography: abnormalities.
– This is an excellent study to evaluate: • It is characterized by an incomplete fusion of
• The differential renal function upper and lower pole moieties resulting in a
• Cortical scars variety of complete or incomplete duplica-
• Drainage efficiency of the dilated col- tions of the collecting system.
lecting system based on washout times • A duplex (duplicated) collecting systems can
• Intravenous pyelogram (IVP): be defined as renal units containing two pyelo-
– This study has been largely replaced by caliceal systems that are associated with a
ultrasound and nuclear renography. single ureter or with double ureters.
– IVP delineates anatomy of the kidney, col- • The two ureters empty separately into the
lecting system, ureter and urinary bladder. bladder or fuse to form a single ureteral
– It also provides subjective estimation of orifice.
relative renal function. • Duplex collecting systems can be unilateral or
• MR urography (MRU): bilateral and can be associated with a variety
– This provides excellent anatomic and func- of congenital genitourinary tract abnormali-
tional evaluation of the renal parenchyma, ties (Figs. 6.2, 6.3, 6.4, 6.5, 6.6, and 6.7).
collecting system and vasculature without • The exact incidence of ureteral duplication is
exposure to radiation. not known but an incidence as high as 8 % in
– MRU is sensitive to motion artifact and children was reported.
necessitates anesthetic sedation of young – Incomplete ureteral duplication was
children. reported in approximately 1 in 25 individu-
• Urodynamic studies: als (Figs. 6.8, 6.9, 6.10, and 6.11).
– This is valuable to assess voiding and blad- – Complete ureteral duplication was reported
der function in those with suspected neuro- in approximately 1 in 125 individuals
genic bladder. (Figs. 6.12 and 6.13).
Figs. 6.2, 6.3, 6.4, 6.5, 6.6, and 6.7 Intravenous urogra- upper renal unit. The lower renal unit is normal. Note also
phy and CT urography showing duplex ureters. In the on the CT urography the associated hydronephrosis and
intravenous urography pictures, each ureter is draing one hydroureters in the lower renal unit while the upper renal
renal unit. There is an associated hydronephrosis in the unit is normal
INCOMPLETE OR
PARTIAL URETERAL
DUPLICATION
Figs. 6.8, 6.9, 6.10, and 6.11 Clinical intraoperative photographs showing duplex ureters. Note the complete and
partial ureteral duplications
Figs. 6.12 and 6.13 Clinical intraoperative photographs showing complete ureteral duplication. Note the associated
dysplastic kidney
• In patients with complete duplication on one – Complete duplication where the two ure-
side, there is a 40 % chance of finding com- ters empty separately into the urinary
plete duplication on the other side. bladder.
• Approximately 10 % of siblings may also be • The upper ureter is more likely to be
affected by complete duplication. associated with ectopic insertion, ure-
• Duplex collecting systems are seen in 0.7 % of terocele, and/or obstruction.
the normal adult population and in 2–4 % of • Caudal or medial ectopia describes the
patients investigated for urinary tract symptoms. ureteral orifice when located at the
• The duplicated ureters can be: proximal lip of the bladder neck or more
– Bifid ureters (partial or incomplete distal.
duplication) • The lower ureter is more frequently
• The two ureters fuse together and insert associated with VUR.
distally as a single ureter into the uri- • The upper pole is one of the components
nary bladder. of the duplex kidney.
• The upper pole ureter drains the upper • Scintigraphy is useful in the assessment of
pole of a duplex kidney. relative renal function and in the detection of
• Similarly, the lower pole of the kidney renal scars. Scintigraphy can reveal differen-
is drained by the lower-pole ureter. tial functioning. However, if the functioning is
• Most patients are asymptomatic, with urinary markedly depressed, imaging is limited.
tract abnormalities being detected incidentally • In the absence of obstruction and/or VUR,
on imaging studies performed for other ureteral duplication anomalies require no spe-
reasons. cific therapy.
• These anomalies are commonly asymptomatic • Symptomatic patients usually have complete
and considered an anatomical variant. ureteric duplication in which the ureters are
• Ureteropelvic obstruction is more common prone to develop obstruction, reflux, and
when a duplex kidney exists and can be inher- infection.
ited in an autosomal dominant pattern. • Duplication anomalies with associated pathol-
• Congenital renal anomalies in patients with ogy, such as VUR or obstruction, require
classic bladder exstrophy occur in 2.8 % of appropriate medical therapy and possible sur-
patients. gical correction.
• The most common anomaly is a duplicated
collecting system, which occurs in approxi-
mately 1.3 % of patients. 6.4.2 Classification
• Duplex collecting systems may be compli-
cated by: • Duplex collecting system or duplex kidney
– Vesicoureteral reflux anomalies can be classified into the following
– Obstruction categories depending on the level or lack of
– Ureterocoele fusion:
• Each of these complications may have adverse – Duplex kidney:
effects on the ipsilateral kidney. • The duplex kidney has a single renal
• A patient’s duplex kidney is almost always parenchyma that is drained by two sepa-
more elongated than his/her nonduplex rate pelvicalcyeal systems
kidney. – Duplex collecting system: The kidney has
• The kidney may be enlarged when hydrone- two pyelocaliceal systems and is associated
phrotic and can be associated with rotational with a single ureter or with a bifid ureter (a
anomalies. partial duplication) or, in the case of a com-
• Magnetic resonance urography (MRU) may be plete duplication, with two ureters (double
used as the primary diagnostic method for ureters) that drain separately into the uri-
assessing a duplex ectopic ureter, as well as the nary bladder.
complications associated with duplex kidneys. – So, a duplex collecting system is a duplex
• If vesico-ureteral reflux exists, the presence of kidney draining into:
an ectopic ureter in a nonfunctioning moiety • Single ureter: Duplex kidneys and
can best be demonstrated using a voiding duplication pelvicalyceal systems unit-
cystourethrogram. ing at the pelviureteric junction (PUJ)
• Antegrade pyelography is useful in patients • Bifid ureter (ureter fissus): two ureters that
with hydronephrosis, to demonstrate the pres- unite before emptying into the bladder
ence of a second ureter and to determine the • Double ureter (complete duplication)
level of ureteric termination. – Bifid collecting system:
• Computed tomography (CT) scanning with • This refers to a duplex kidney with the
contrast is valuable in the evaluation of an two separate pelvicalyceal collecting
intravesical ureterocele, either orthotopic or systems uniting at the PUJ or as bifid
ectopic. ureters.
• Two pelvicalyceal systems join at the

ureteropelvic junction (bifid pelvis), or • Duplex collecting system: A duplex kid-
two ureters join before draining into the ney draining into:
urinary bladder (bifid ureters). – A single ureter: Duplex kidney with
– Double/duplicated ureters (or collecting pelvicalyceal system uniting at the
system): pelviureteric junction.
• This is characterized by two ureters that – Bifid ureters: Two ureters that unite
drain separately into the bladder or gen- before emptying into the urinary
ital tract. bladder.
• Two ureters open separately into the – Double ureters (Complete duplication)
renal pelvis superiorly and drain sepa- • Bifid collecting system: A duplex kid-
rately into the bladder or genital tract. ney with the two separate pelvicalyceal
• Upper and lower pole ureters drain a collecting system uniting at the pelvi-
duplex kidney’s upper and lower poles, ureteric junction or as bifid ureters
respectively. (Incomplete ureteral duplication).
• As a result of these anatomic abnormalities: • Double/Duplicated ureters: Two ureters
– The duplicated ureters may be seen extend- that drain separately into the urinary
ing a variable distance down to the urinary bladder or genital tract (Complete ure-
bladder. teral duplication).
– Obstruction of the upper pole moiety down
to the bladder may be seen, often associ-
ated with a ureterocoele.
– Vesicoureteral reflux into the lower pole • These are seen in patients with completely
moiety may be seen. This is often due to duplicated ureters.
distortion in its insertion by an associated • Duplication can be variable.
ureterocoele. • At one end of the spectrum, there is merely a
– Ectopic insertion of the upper pole moiety duplication of the renal pelvis, draining via a
e.g. into the prostatic urethra in males or single ureter.
vaginal vault in females. • At the other extreme, two separate collecting
– If reflux is significant, evidence of reflux systems drain independently into the bladder
nephropathy may be evident. or ectopically.
• Duplex systems may be unilateral or bilateral
and can be associated with a variety of other
6.4.3 Clinical Features congenital abnormalities of the urinary tract.
• Duplex systems can be associated with
• Most duplicated systems are asymptomatic Fanconi anemia.
and diagnosed incidentally.
• Duplex collecting system may be complicated by
infection, vesicoureteral reflux or obstruction. 6.4.4 Investigations
• Occasionally, hydronephrosis can be severe
enough to result in flank discomfort, pain or • Intravenous urography (IVU) (Figs. 6.14 and
even a palpable mass. 6.15):
– This can demonstrate both collecting sys-
tems, but a poorly functioning system may
Classification of Duplex Collecting System
not excrete contrast and will not be
• Duplex kidney: Two separate pelvicaly-
visualized.
ceal system draining a single renal
– In such a situation, the functioning lower
parenchyma.
pole moiety will be inferiorly displaced,
Figs. 6.14 and 6.15 Intravenous urography showing partial (incomplete) ureteral duplication on the right side
taking on the so-called “drooping lily system, and the presence of a straight infe-
appearance”. rior border help to differentiate a duplex
– This may be confused with an upper pole collecting system from a renal mass.
mass or cyst. – Anomalies of the ureter, such as partial or
– A patient’s duplex kidney is usually longer complete ureteral duplication, may be
than his/her nonduplex kidney. demonstrated.
– The parenchymal thickness of one of the • Abdominal and pelvic ultrasound:
poles of the duplex kidney is less than that – Ultrasound is useful when the duplex sys-
of the other pole. tem is associated with obstruction/
– The calyces are asymmetric hydronephrosis.
– An ectopic, upper pole ureteric insertion – Ultrasound is also useful in detecting asso-
can produce a nonopacified segment. This ciated ureterocele.
mass effect results in the “drooping lily” – With the use of ultrasound it may be diffi-
sign with the depression of the lower pole cult to differentiate between partial and
pelvicaliceal system. complete duplication.
– If the lower pole of the duplex kidney is – The duplex kidney appears as two central
functioning poorly or not at all, the lower echo complexes with intervening renal
pole collecting system may not opacify, parenchyma.
and no discernible parenchyma will sur- – Hydronephrosis at one pole is suggestive
round it (nubbin sign). The kidney’s of a duplex kidney.
appearance may consequently resemble – Although hydronephrosis can occur at either
that of a nonduplex kidney with a lower pole, it is more common in the upper pole.
polar mass or renal infarct. – Occasionally, two distinct collecting sys-
– A reduction in the number of calyces, the tems and ureters can be observed on ultra-
depiction of a portion of the collecting sonographic images.
– Differentiating an atrophied lower pole a duplex kidney is of great value in the

moiety of a duplex kidney (nubbin) from management of duplex kidney.
other renal masses is difficult. • MR urography (Figs. 6.16, 6.17, 6.18, and
– The nubbin of tissue from the atrophied 6.19):
lower pole of a duplex kidney cannot be – This may be used as a primary diagnostic
confidently differentiated from other method in assessing a duplex ectopic ureter
masses. and complications associated with duplex
• CT urography: kidneys.
– CT urography is able to delineate essen- • An ectopic ureter extending from a poorly
tially all duplex abnormalities especially if functioning moiety of a duplex kidney, invisi-
reconstruction images are made. ble on other imaging, may be observed with
– The intervening renal parenchyma in a MR urography
duplex kidney lacks a collecting system • Micturating cystourethrography:
and major vessels, and because of this it is – The intravesical ectopic ureter of a nonvi-
described as having a “faceless kidney” sualized moiety is better demonstrated
appearance. using voiding cystourethrogram.
– A duplicated renal collecting system can be – In patients with hydronephrosis, antegrade
suspected if a faceless kidney is identified. pyelography is useful for demonstrating
– CT scan can help to determine if an obstruc- the presence of a second ureter and for
tion exists and can aid in assessing the determining the level of termination.
renal parenchyma thickness.
– CT scan can also help to determine if the
insertion of the duplex ureter is intravesical 6.4.5 Treatment and Prognosis
or extravesical.
– CT scan can demonstrate the collecting • An asymptomatic duplex kidney usually does
system in the nubbin or the mass effect of not require any treatment.
tissue at the pole. • Surgical treatment is indicated in the presence
– CT scan is superior to ultrasonography and of complications.
excretory urography in diagnosing the • These complications include:
lower pole nubbin. – Vesicoureteral reflux into lower pole
• Nuclear scan: moiety
– Renal scintigraphy is useful to evaluate – Marked hydronephrosis of the upper pole
renal function, particularly when planning moiety may have mass effect or become
corrective surgery. infected
– Renal scintigraphy is less useful to identify • Antibiotic prophylaxis is given to newborns
non-obstructed duplex systems. with hydronephrosis or in patients who
– Duplex kidneys appear as two separate col- present with urinary tract infection (UTI)
lecting systems on the same side of the until the diagnosis is made and reflux is
body. ruled out.
– Scintigraphy may demonstrate reflux up • Antibiotic prophylaxis is often continued in
the ureter in a nonfunctioning duplex kid- patients with obstructed systems and in infants
ney with ureteral duplication. with dilated nonobstructed systems.
– The presence of a duplex kidney and ure- • Duplicated collecting systems with reflux are
teral duplication, suggested by excretory managed conservatively with antibiotic pro-
urographic or ultrasonographic images, can phylaxis until the reflux spontaneously
be confirmed with scintigraphy. resolves or until the child is older
– The use of dimethyl succinic acid (DMSA) (6–12 months), at which time surgery may be
scanning to assess parenchymal function in more easily accomplished.
Figs. 6.16, 6.17, 6.18, and 6.19 MRU showing bilateral duplex kidneys. Note the associated hydronephrosis and
hydroureters
• In infants with duplicated systems and a well- is bigger and a ureteral reimplantation with or
functioning but obstructed upper-pole moiety without ureteral tailoring is more feasible.
or an obstructed ectopic single-system ureter, • In infants with a duplicated system and no
urinary diversion (A cutaneous ureterostomy) reflux is present in the lower-pole system, a
may be the treatment of choice until the bladder ureteroureterostomy is an option.
6.5 Ectopic Ureter 197
• In those with upper-pole system that serves a • The ejaculatory duct

duplicated ureterocele: typically makes up • The rectum rarely
less than 30 % of the unilateral renal function, – In females, the ectopic ureter drains into:
and preservation of this function is usually not • The lower urinary bladder
critical. • The urethra
– If this poorly functioning moiety is not • The vestibule
associated with reflux in other moieties, the • The vagina.
best approach is excision. • The uterus or Wolffian duct remnants
– If this poorly functioning moiety serves a rarely
decompressed ureterocele with no reflux, • An ectopic ureter is a congenital renal anom-
there is no indication for removal. aly that occurs as a result of abnormal caudal
• Each ureter drains a separate renal moiety. migration of the ureteral bud during its inser-
– If only one moiety is involved and is poorly tion to the urinary bladder.
functioning, a single-stage nephrectomy or • Failure of separation of ureteral bud from
heminephrectomy is usually curative. Wolffian duct results in caudal ectopia.
– The likelihood that this upper-tract • Ectopic ureter is commonly a result of a dupli-
approach will be curative diminishes as the cated renal collecting system, a duplex kidney
number of other moieties involved with with two ureters.
either reflux or obstruction increases. – One ureter drains properly to the bladder
– In this case, a lower-tract approach in – The duplicated ureter presenting as
which all problematic ureters can be simul- ectopic
taneously treated is a better option. • The Weigert-Meyer rule:
– In the case with complete duplication, the
ureter draining the upper moiety inserts
6.5 Ectopic Ureter more medial and more inferior to the lower
moiety ureter and liable for obstruction
6.5.1 Introduction while the ureter draining the lower moiety
is liable for reflux.
• Normally the ureters drain via the internal ure- • Ectopic ureter can be associated with:
teral orifice at the trigone of the urinary – Ectopic ureter may be solitary
bladder. – Approximately 80 % of ectopic ureters are
• Ectopic ureter occurs when the ureter drains to associated with duplex kidneys
an abnormally located (ectopic) orifice. – Ectopic ureter may be part of complex con-
• Bilateral single-system ureteral ectopia is rare genital anomalies
and usually coexist with other urinary tract – Hydronephrosis
anomalies including VUR, renal dysplasia, – Ureterocele
and rudimentary bladder development. – Renal dysplasia
• Ectopic ureter (or ureteral ectopia) is a con- – Frequent urinary tract infections
genital malformation where the ureter, rather – Urinary incontinence (usually continuous
than terminating at the urinary bladder tri- drip incontinence).
gone, terminates at a different abnormal loca- • Ectopic ureters are found in 1 of every 2,000–
tion. This abnormal location is as follows: 4,000 patients.
– In males, the ectopic ureter drains into: • Approximately 10 % are bilateral.
• The lower urinary bladder • Ectopic ureters occur more frequently in
• The posterior urethra females than in males (F: M 10:1 or 6:1).
• The seminal vesicle • In females, more than 80 % of ectopic ureters
• The vas deferens drain duplicated systems.
• In males, most ectopic ureters drain a single the part of the urogenital sinus that will
system. become the urethra.
• Approximately 80 % of all ectopic ureters • The mesonephric duct eventually becomes the
drain the upper pole of a duplex kidney. epididymis, vas deferens, ejaculatory duct,
and seminal vesicles in the male and the
Gartner’s duct in the female.
Sites of Ectopic Ureters • Ureteral ectopia occurs when the orifice of the
• In males, the ureters always terminate developing ureter does not migrate into its
proximal to the external sphincter and proper location and takes its final position in
may be found at the: an abnormal location.
– Bladder neck/prostatic urethra (48 %) • As a result of this, Ectopic ureters may termi-
– Seminal vesicle (40 %) nate in:
– Ejaculatory duct (8 %) – A male vestige of the mesonephros, such as
– Vas deference (3 %) the epididymis, vas deferens, ejaculatory
– Epididymis (0.5 %) duct, or seminal vesicle.
• In females, the ureters may terminate at – Gartner’s duct (duct of the epoophoron),
the: the female vestigial remnant of the meso-
– Bladder neck/urethra (35 %) nephric duct, which resides within the
– Vestibule (30 %) muscular wall of the genital tract extending
– Vagina (25 %) from the internal cervical os along the lat-
– Uterus (5 %) eral or anterolateral vaginal wall to the
hymen.
– Nearby vestigial remnants of the Müllerian
• Single-system ureteral ectopia reveals wide- (paramesonephric) duct, such as the utricu-
spread renal dysplasia in 90 % of affected lus in the male and the upper vagina, cer-
kidneys. vix, and uterus in the female.
• Duplicated-system ureteral ectopia reveals – The urethra in both sexes.
renal dysplasia in approximately 50 % of • Ureteral ectopy into the rectum is rare, but it
affected renal moieties. may occur when the mesonephric duct inserts
posteriorly on the cloaca and/or following
inappropriate division of the urorectal
6.5.2 Embryology septum.
and Pathophysiology • The persistent common excretory duct is
another rare variant of ectopia (an ectopic vas
• In normal development, a single ureteral bud deferens opens into a ureter, culminating in a
originates from the excretory duct of the pro- common duct that opens to the trigone).
nephros and mesonephros, the mesonephric • In ureteral duplication, two ipsilateral ureteral
duct. buds migrate separately and simultaneously
• This complex forms adjacent to the metaneph- toward the urogenital sinus.
ric blastema, the precursor to the kidney. • According to the Weigert-Meyer law, the
• The ureteral bud migrates and rotates toward lower pole ureter migrates toward the vesical
the portion of the urogenital sinus that will portion of the urogenital sinus ahead of the
become the bladder and acquires a separate upper pole ureter.
orifice from the mesonephric duct. – If both orifices reach the bladder, the ori-
• Once in the vesical portion of the urogenital fice of the lower pole ureter is superolateral
sinus, the orifice migrates superolaterally with to the orifice of the upper pole ureter.
respect to the primitive trigone as the meso- – Ectopia of one or both ureters may occur;
nephric duct rotates caudally and medially to however, ectopia of only the upper pole
ureter is usually present, because it is the sec- • The diagnosis of an ectopic ureter associated
ond ureter to be incorporated onto the with a duplex kidney can be difficult.
trigone. • The upper pole of a duplex kidney with an
– Its late arrival to the urogenital sinus causes ectopic ureter may be very small and poorly
the migrating mesonephric duct to carry functioning. Its small size makes it difficult to
the ureter to an abnormal location outside identify on morphological imaging. As a result
the bladder. of its poor function, there is no or minimal
• Additional anomalies of the ipsilateral or con- uptake of the tracer when isotope studies are
tralateral system(s) are known to occur in performed.
association with upper and/or lower pole ure- • Finding the opening to an ectopic ureter at
teral ectopia, such as: cystoscopy or vaginoscopy is also difficult.
– Ureterocele
– Ureteropelvic junction obstruction
– Renal ectopia 6.5.3 Clinical Features
– Renal dysplasia
– Vesicoureteral reflux • Ectopic ureters are often found incidentally on
• In females, the most common sites for an radiologic imaging studies.
ectopic ureteral orifice, in decreasing order, • The symptomatology in these patients depends
are: on the location of the ureteral orifice, its rela-
– The urethra tionship to the urinary sphincter, and the com-
– The vestibule petence of the bladder neck.
– The vagina • In symptomatic patients, common presenta-
– The cervix tions usually include:
– The uterus – Incontinence
– The Gartner’s duct – Flank pain
– A urethral diverticulum – Hematuria
• In males, the most common sites for an ecto- – Pelvic/perineal discomfort
pic ureteral orifice in descending order, are: – Infection
– The posterior urethra – Vaginal discharge
– The prostatic utricle – Hydrocolpos
– The seminal vesicle – Epididymo-orchitis
– The ejaculatory duct – Painful intercourse
– The vas deferens – Ejaculatory pain
– The epididymis – Prostatitis
• In the male, the most common site is the pos- – Seminal vesiculitis
terior urethra, occurring in approximately – Hemospermia
50 % of cases. – Change in bowel habits
• Other sites include the seminal vesicle – A mass in the abdomen, rectum, urethra,
(approximately one-third), vas deferens, and vagina
bladder neck, prostate to the level of the ejacu- – Irritative and obstructive voiding difficul-
latory duct orifice, and epididymis. ties – with or without incontinence
• In males, the ectopic ureter is always above • In males, incontinence does not occur because
the external urinary sphincter. ectopic ureteral orifices always terminate
• Therefore, males with an ectopic ureter do not proximal to the external sphincter. Extremely
have urinary incontinence, but typically pres- rare, the ectopic ureter opens in the urethra
ent secondary to a prenatal diagnosis of hydro- just distal to the external sphincter.
ureteronephrosis or symptomatic urinary tract • The diagnosis of ectopic ureter is difficult and
infection. even when symptoms are present, it is common
for the diagnosis of ureteral ectopia to be and so is appropriately treated by upper pole
delayed several years. hemi-nephrectomy.
• Clinical examination of a girl with an ectopic • Complete uretrectomy may be associated with
ureter may identify continuous dripping of increased morbidity.
urine from the introitus. • Retaining the distal ureteric stump on the
• There may be perineal irritation from continu- other hand carries a less than 10 % chance of
ous leaking. re-operation for distal ureteric removal. This
• Careful targeted cystoscopy and vaginoscopy however will reduce the morbidity from a
may locate an ectopic ureteric opening, but complete ureterectomy.
identification can be difficult and the opening • With the recent development in minimal inva-
easily missed. sive surgery, laparoscopic hemi-nephrectomy
is feasible and safe. Laparoscopic lower pole
hemi-nephrectomy may be associated with
6.5.4 Diagnosis risks of retroperitoneal fluid collection, loss of
renal tissue and hypertension.
• Intravenous urography (IVU): • Where upper pole function is preserved, an
– It can defect abnormal ureteral insertion alternative to hemi-nephrectomy is ureteric
and associated anomalies such as renal re-implantation.
duplication. – In these cases, both ureters from the duplex
– In complete duplex kidney and ureter, the kidney should be re-implanted together.
ectopic ureter usually drains the upper moi- – Re-implantation, however, can be avoided
ety and may be associated with ureterocele by draining the upper pole into the lower
and obstruction. pole system either with an uretero-
• Voiding cystourethrogram (VCUG): ureterostomy or an uretero-pyelostomy.
– Usually the ectopic ureter is associated – Currently, laparoscopic uretero-
with vesico-ureteric reflux, which can be ureterostomy and uretero-pyelostomy have
detected and graded with VCUG. been reported to be feasible and safe.
• Abdominal and pelvic ultrasound: • The surgical management of systems with
– This is useful in detecting associations and ectopic ureters depends on several factors:
complications of ectopic ureter such as – The function of the involved (usually the
duplex kidneys, hydronephrosis and upper pole moiety) and uninvolved renal
ureterocoele. segments.
• MR urography (MRU): – Single versus duplicated systems
– This is valuable in diagnosing ectopic – The site of terminal insertions of the ureters
ureters. – Coexistent morbidities, such as infections,
– The ureter and its insertion may be reflux, pain, infertility, incontinence, masses,
visualized. and associated anatomic anomalies.
– MRU is also useful in detection of other • Surgical considerations usually include:
anomalies such as renal duplication, ure- – Total nephrectomy
terocoele and vertebral anomalies. – Upper pole partial nephrectomy
– Ureterectomy
– Nephroureterectomy
6.5.5 Surgical Treatment – Pyelopyelostomy
– Pyeloureterostomy
• Symptomatic ectopic ureters are treated – Ureteroneocystostomy
surgically. – Ureteroureterostomy
• The upper pole kidney associated with an – Percutaneous decompression
ectopic ureter is usually poorly functioning – Endoscopic incision
• With respect to the kidney, total and segmen- cystoscopy can fail to identify the ectopic
tal renal function must be considered when ureter in two-thirds of the patients.
contemplating nephron-sparing surgery. – If an ectopic ureter is associated with a
• In general, the more ectopic the ureteral ori- single system and the kidney is severely
fice, the more dysplastic the involved moiety dysplastic or poorly functioning, the rec-
of the kidney. ommended treatment is nephrectomy with
• The fate of the distal ectopic ureter is partial or total ureterectomy.
controversial. – If the involved kidney is functioning satis-
– In most cases, it can be left in situ and factorily, the recommended treatment is
widely spatulated so that dissection does ureteral reimplantation.
not compromise pelvic structures and/or – In rare instances of bilateral single-system
the blood supply to the ipsilateral lower ectopic ureters, when the bladder capacity
pole ureter of a duplicated system. is actually adequate for urination, bilateral
– Primary or delayed distal stump ureterec- ureteral reimplantation is performed.
tomy may be needed in some situations: – If the bladder neck is poorly developed in
• Severe hydronephrosis of the remnant association with the ureteral ectopia,
ureter leading to obstruction of the ipsi- bladder neck reconstruction (Young-Dees-
lateral duplicated ureter. Leadbetter bladder neck plasty) may be
• Ectopic insertion into the genital or necessary.
gynecologic tracts causing infertility, • Bilateral ectopic ureter:
pain, or infection. – Bilateral ectopic ureters are a rare and dis-
• Reflux leading to recurrent infection of tinct malformation affecting girls.
the ureteral stump, pain, or persistent – Neither ureter drains into the bladder which
mass. is small with a poorly developed sphincter.
– Distal ectopic ureterectomy may be inevi- – It is possible that during development the
table if there is reflux into the ectopic abnormal origin of both ureteric bud results
ureter. in poor mesenchymal induction of the uro-
– Reflux into the ipsilateral ureter was also a risk genital structures. This results in failure of
factor, requiring secondary surgery in 40 %. normal development of the bladder and the
• Single system ectopic ureter: bladder neck.
– About one fifth of ectopic ureters are asso- – Both the sphincter and reservoir functions
ciated with single system kidneys. of the bladder are severely affected.
– Single system ectopic ureters are fre- – Thus although the child may present with
quently associated with other congenital incontinence, ureteric re-implantation will
problems, including anorectal, esophageal fail to correct the incontinence and only
and renal tract anomalies. 20 % became continent.
– About half of those with single system – Achieving continence requires:
ectopic ureters ae discovered during inves- • Ureteric re-implantation
tigation of other anomalies. • Improvement of bladder storage
– The remaining half present with either • Improvement in bladder outlet
incontinence or infection. resistance
– Renal dysplasia is common but those with – Ureteric re-implantation is difficult because
single system ectopic ureter are associated of the small bladder size.
with kidneys with reasonable function. – Creating a window between a distal ureter
– Diagnosis of single system ectopic ureters and the bladder may, allow reasonable
can be difficult. bladder capacity to develop and possibly
– Micturating cystogram can demonstrate avoid bladder outlet procedures and
reflux in only half of the patients and initial augmentation.
– Bladder capacity may be improved with – If the upper-pole moiety is nonfunctional, a

enterocystoplasty. partial nephroureterectomy is performed
– A variety of bladder outlet procedures have and the upper-pole ureter is removed to the
been described: pelvic brim.
• Young-Dees-Leadbetter bladder neck – If patients have coexisting upper-pole
reconstruction VUR, the ureteral stump should be ligated
• Kropp procedure to prevent reflux of urine into the
• Pubovaginal sling retroperitoneum.
• Bladder neck closure – The more distal the ureter insertion, the
• Artificial urinary sphincter worse the prognosis.
• Duplex system:
– Treatment depends on the function of the
involved upper pole and whether VUR is 6.6 Ureterocele
present.
– If function is adequate, an ureteropyelos- 6.6.1 Introduction
tomy (upper-pole ureter to lower-pole renal
pelvis) or ureteroureterostomy (upper-pole • A ureterocele is a congenital saccular dilata-
ureter to lower-pole ureter) is performed if tion of the distal segment of the ureter
no VUR is noted in the lower pole ureter. (Figs. 6.20, 6.21, 6.22, and 6.23).
– In patients with a functioning upper-pole • This anomaly most frequently involves the
system and coexisting lower-pole VUR, upper pole of a duplex system.
a common sheath ureteral reimplantation is • A ureterocele contained within the bladder is
performed. called an orthotopic ureterocele.
URETEROCE
URETEROCE
Figs. 6.20 and 6.21 Clinical intraoperative photographs showing ureterocele. Note the associated severely dilated
ureter. Note also the small atrophic dysplastic kidney
Figs. 6.22 and 6.23 Pelvic ultrasound showing right and left ureterocele
6.6 Ureterocele 203
• Sometimes, the ureterocele extends beyond – Sphincterostenotic ureterocele (6 %):

the bladder into the urethra. • The ureterocele has an orifice at the
• This is called an ectopic ureterocele. level of the sphincter.
• These patients may present with a cystic mass • Its narrow orifice further impedes its
at the urethral meatus representing a prolapsed drainage so that the ureterocele remains
ureterocele. dilated and obstructs the bladder
• Ureteroceles are often associated with obstruc- outlet.
tion and VUR. – Blind ureterocele (5 %):
• The incidence of ureterocele is approximately • This form of ureterocele extends
1 in 4,000 children. under the trigone and into the bladder
• Approximately 80 % occur in females. outlet.
• Approximately 10 % are bilateral. • No opening is identifiable.
• Approximately 80 % are associated with • The dilated ureterocele can cause severe
duplicated collecting systems with single sys- bladder outlet obstruction.
tem ureteroceles being more common in males – Non-obstructive ureterocele (5 %):
and adults. • This type of ureterocele lies entirely
• Indications for surgical interventions include: within the bladder, and has a large open-
– Obstruction ing which does not impede drainage of
– Urosepsis or compromised renal function the ureterocele.
may necessitate urgent decompression prior – Caecoureterocele (5 %):
to definitive surgical reconstruction • This form of ureterocele extends sub-
mucosally into the urethra.
• The orifice of the ureterocele lies more
6.6.2 Classification proximally either in the urethra or the
bladder.
• The AAP classification of ureteroceles: • A “tongue” of submucosal ureterocele
– Intravesical ureteroceles lies caudal to the opening.
– Ectopic ureteroceles • If its opening is small, filling of the ure-
• Stephens et al. classification of ureteroceles: terocele may obstruct the bladder
– Stenotic ureterocele (40 %): outlet.
• This is the most common type of • If the ureterocele has a large opening
ureterocele. (either naturally or iatrogenically) the
• The ureterocele lies within the bladder. tongue of the caecoureterocele will fill
• Its orifice lies within the trigone and is by reflux during voiding and may
obstructive. obstruct the urethra.
• It corresponds to an intravesical
ureterocele.
– Sphincteric ureterocele (30 %): Classification of Ureteroceles
• In this form of ureterocele, a rather dilated • The AAP classification:
ureter courses through the submucosa of – Intravesical ureterocele
the bladder, and adopts a more normal – Ectopic ureterocele
caliber as it travels into the urethra. • The Stephens et al. classification:
• It has an opening at the level of the – Stenotic ureterocele (40 %)
sphincter. – Sphincteric ureterocele (30 %)
• Its orifice is not narrow, but drainage – Sphincterostenotic ureterocele (6 %)
from the ureterocele is impaired by con- – Blind ureterocele (5 %)
traction of the sphincter. – Non-Obstructive ureterocele (5 %)
• The associated ureterocele can be very – Caecoureterocele (5 %)
large.
6.6.3 Clinical Features – More than half will have abnormally large
bladders, and residual volumes are
• The exact incidence of ureterocele is not common.
known and at post-mortem, ureterocele was – Stones have been observed in a large pro-
estimated to occur 1 in 500–4,000. portion of adult patients presenting with
• In patients with duplex kidneys, ureterocele is ureterocele.
found in 5–20 %.
• With the wide spread use of antenatal ultra-
sound, half to three quarters of ureteroceles 6.6.4 Investigations and Diagnosis
are detected antenatally.
– It is common for ureteroceles to obstruct • The aims of investigating patients with ure-
the upper pole of the affected kidney from teroceles are:
which they have arisen. – To confirm the diagnosis
– The lower pole ureter may be obstructed by – To determine its structure (intravesical or
the dilated upper pole ureter. ectopic)
– A ureterocele that obstructs the bladder – To identifying coexisting pathology:
outlet will affect the contralateral kidney as • VUR
well. • Lower pole and bladder outlet
• Ureteroceles may be associated with vesico- obstruction
ureteral reflux which affect the ipsilateral • Abdominal and pelvic ultrasound (Figs. 6.24,
lower pole in half, and the contralateral kid- 6.25 and 6.26):
ney in a quarter. – The ureterocele and its associated dilated
• Abnormal bladder function is common in ureter and upper pole are usually identified
children with ureterocele. on ultrasound.
Figs. 6.24, 6.25, and 6.26 Abdominal and pelvic ultrasounds showing right ureterocele
6.6 Ureterocele 205
– It is important not to confuse a dilated dis- • A Dimercaptosuccinic acid (DMSA) radionu-

tal ureter that is adjacent to the bladder cleotide scan:
with a ureterocele. – This is useful to confirm poor function in
– A ureterocele that is collapsed may be the upper pole and also provides a baseline
missed at the time of ultrasound scanning. function prior to surgery.
• Micturating cystourethrogram (MCUG): • CT urography and Magnetic resonance urog-
– This is an important investigation in raphy (MRU):
patients with suspected ureterocele. – These can define the anatomy more clearly
– It identifies its size, site and the relationship including the site of the ureterocele, ureter
of the fundus and base of the ureterocele to and associated renal pathology (Figs. 6.28
the bladder neck and urethra, indicating pos- and 6.29).
sible bladder outlet obstruction (Fig. 6.27). • Cystoscopy:
– MCUG is useful in detecting associated – Cystoscopy is valuable to diagnose
VUR. ureterocele.
– Care should be taken that an everted ure- – It is useful to distinguish intravesical from
terocele is not miss-diagnosed as a paraure- ectopic ureteroceles.
teric diverticulum. – When performing cystoscopy care must be
taken not to obliterate the ureterocele; ide-
ally the patient should be well hydrated,
and irrigation flow kept to a minimum.
6.6.5 Treatment
• There are several treatment options that can be

offered to a patient with a ureterocele
(Figs. 6.30, 6.31, and 6.32).
• The treatment options include:
– Conservative treatment
– Ureterocele puncture
– Upper pole hemi-nephrectomy
– Ureterocele excision with bladder neck
repair and re-implantation
• Ureterocele puncture is appropriate for emer-
gency decompression of acutely infected sys-
tems and for intravesical ureteroceles.
• Upper pole hemi-nephrectomy carries a good
Fig. 6.27 A delayed film of MCUG showing a filling success rate where there is no associated
defect in the bladder representing a ureterocele reflux.
Figs. 6.28 and 6.29 CT urography showing ureterocele. Note the associated dilated ureter
Figs. 6.30, 6.31, and 6.32 Clinical intraoperative photographs showing a very large ureterocele causing obstruction.
Note the associated dilated ureter and the small atrophic dysplastic kidney
• Conservative treatment: – Upper pole hemi-nephrectomy will elim-

– Expectant conservative treatment of antena- inate an obstructed system predisposed
tally detected ureteroceles may be successful. to urinary tract infection and suction of
– This approach avoid potentially difficult the distal ureter at the time will lead to
surgery and its complications. collapse and decompression of the
– Leaving dysplastic renal tissue in situ ureterocele.
may not pose an increased risk of – Co-existing VUR to the lower pole is then
hypertension. expected to resolve in the majority of
– The main concern over expectant manage- patients.
ment of ureteroceles is the predisposition – One important advantage of hemi-
of an obstructed hydronephrotic kidney to nephrectomy is that difficult surgery at the
infection. bladder neck and distal ureter is avoided.
• Upper pole hemi-nephrectomy: – With this approach, re-operation is avoided
– The upper pole of the kidney associated in 85 % of patients.
with a significant ureterocele usually has – Bladder dysfunction seen in some of these
minimal function. patients is probably an inherent problem
6.6 Ureterocele 207
associated with ureterocele and not related – The most common indication for re-
to hemi-nephrectomy. operation is VUR.
– Heminephrectomy may be complicated by – This can affect half the patients having a
incontinence, UTI, diverticula and even ureterocele puncture and commonly affects
bladder outlet obstruction. the upper pole in about a third.
• Ureterocele puncture/endoscopic treatment: – Treatment of VUR following ureterocele
– Endoscopic treatment of ureteroceles by puncture is reimplantation.
puncture using cystoscopy is an alternative – Cystoscopic injection therapy has a success
approach with much lower perioperative rate of 60–70 %.
morbidity. • Bladder neck reconstruction:
– It can almost be performed as day-case – The aim of bladder neck reconstruction is
surgery. to correct the associated anatomical
– Endoscopic puncture provide emergency abnormalities.
relief of obstruction in a child presenting – Reconstruction may be performed as either
with acute infection. the primary or secondary treatment.
– Endoscopic puncture has a high success – Reconstruction surgery is difficult, espe-
rate for intravesical ureteroceles, and for cially when performed on a young infant.
these patients endoscopic puncture can be – In early life, ureterocele puncture may be
offered as a definitive treatment. performed to control the risk of UTI.
– This however is not the case for those with – Reconstruction can then be performed at an
ectopic ureteroceles where a high rate of older age when reconstruction surgery is
re-operation should be expected. In these easier.
patients, endoscopic ureterocele puncture – Alternatively reconstruction has been per-
should be considered as part of a staged formed as a primary procedure with good effect.
procedure. Endoscopic puncture in these – Reconstruction may include all or part of
patients makes subsequent reconstructive the following:
surgery easier, or enable VUR to be con- • Excision of the ureterocele
trolled endoscopically. • Repairing the weakness of the bladder
– This puncture may need to be repeated in neck and bladder wall
10–20 % of patients. • Re-implantation of the associated ureters
– Ureterocele puncture may be followed by • Hemi-nephrectomy of a poorly func-
recovery of some upper pole function. tioning upper pole.
– Recovery of upper pole function is likely to • Marsupialization of the ureterocele,
be limited if underlying poor function is rather than its complete excision, may
because of dysplasia rather than obstruction. be performed to avoid difficult dissec-
– The main criticism of ureterocele puncture as tion in the urethra.
a treatment modality is the need for further • The benefit of reconstruction is that the
surgery, despite adequate decompression. functional problems associated with the
– It was reported that about 47 % of patients ureterocele can all be corrected. These
with ureterocele treated by endoscopic include:
puncture required further surgery. The risk – VUR
of reoperation increases up to 70 % with – Sphincter weakness
extended follow-up. – Bladder outlet obstruction
– The chance of re-operation is higher: – Uretero-ureterostomy:
• When the ureterocele is ectopic com- • This is a simple technique to treat chil-
pared to intravesical dren with ureterocele.
• In a duplex system compared to a single • Uretero-ureterostomy has less morbid-
system ity when compared to heminephrectomy
• If there is pre-existing reflux and or reconstruction.
• The procedure is based on anastomos- • These include:

ing the upper pole ureter to the lower – Urosepsis
pole to provide effective drainage. – Severe compromise in renal function.
• Uretero-ureterostomy may be combined • Endoscopic decompression in cases of ectopic
with ureteric re-implantation of the less ureterocele constitutes definitive treatment in
dilated ureter with good outcome. only 10–40 % as there is frequently associated
• One of the advantages of uretero- VUR, which often requires subsequent surgi-
ureterostomy is that it can be performed cal correction.
through a small incision or • Options for open surgical reconstruction
laparoscopically. include ureteropyelostomy, ureteroureteros-
• Single system ureterocele: tomy, excision of ureterocele and ureteral
– A fifth of all ureteroceles occur in single reimplantation, or upper-pole heminephrec-
systems. tomy with partial ureterectomy and uretero-
– Single system ureteroceles are most com- cele decompression.
monly intravesical. • In patients with a single-system ureterocele
– The associated kidneys often have reason- and an associated nonfunctioning kidney, a
able function. nephroureterectomy may be performed.
– The majority of single system ureteroceles • In the case of obstructive ureteroceles, treat-
presenting in childhood are detected ment to relieve obstruction optimizes preser-
antenatally. vation of renal function as chronic obstruction
– The treatment of single system ureterocele can lead to renal deterioration.
depends on the presence or absence of
obstruction.
– Conservative treatment: 6.7 Vesicoureteral Reflux (VUR)
• If there is no obstruction or reflux of the
affected kidney then non-surgical con- • VUR is retrograde flow of urine from the uri-
servative treatment is appropriate. nary bladder into the ureter and/or kidney
– Surgical treatment: (Figs. 6.33 and 6.34).
• If the ureterocele impairs the drainage • One of the common complications of VUR is
of an affected kidney then surgery is urinary tract infection.
indicated. • This causes reflux-induced renal injury.
• Transurethral endoscopic puncture or • Reflux that is secondary to high bladder pres-
incision of the ureterocele is much more sures such as those occurring in patients with
likely to be successful in simplex sys- posterior urethral valves (PUV) or bladder
tem ureteroceles than in duplex outlet obstruction is frequently associated
kidneys. with renal injury.
• Re-operation rates for ureteroceles in • Reflux-induced renal injury may range from
single systems are low (0–25 %). clinically silent focal scars to generalized scar-
ring and renal atrophy (reflux nephropathy).
6.6.5.1 Surgical Interventions • This may lead to:
• Treatment of the ureterocele is based upon – Hypertension (renin-mediated)
relief of obstruction. – Renal insufficiency
• Endoscopic puncture may be used in cases in – End-stage renal disease
which urgent decompression is required (e.g. • VUR may be associated with areas of renal
urosepsis, severe compromise in renal func- dysplasia or hypoplasia.
tion), or it may be used as definitive therapy in • These are seen in the absence of urinary tract
the case of a single-system intravesical infection and may be due to abnormal renal
ureterocele. development.
6.7 Vesicoureteral Reflux (VUR) 209
Figs. 6.33 and 6.34 Micturating cystourethrograms showing severe bilateral reflux
• The incidence of VUR in otherwise healthy • Secondary VUR:

children is approximately 1 %. – This is secondary to several factors that
• The incidence is approximately 40 % in affect the uretrovesical junction.
patients undergoing evaluation for UTI. – These factors include (Figs. 6.35, 6.36, and
• The reported risk of reflux in a sibling is 6.37):
27–43 %. • Loss of UVJ compliance during UTI
• Approximately 50 % of the offspring of • Bladder diverticulum
women with reflux will also have VUR. • Ureterocele
• Normally, the distal ureter enters the urinary • Neurovesical dysfunction or neurogenic
bladder through a submucosal tunnel. bladder
• The submucosal tunnel length is the most • Bladder outlet obstruction
important component of a competent uretro- • Indications for surgical interventions:
vesical junction. – Absolute indications:
• A competent uretrovesical junction provides a • Progressive renal injury
one way valve that allows antegrade passage of • Documented failure of renal growth
urine from the ureter into the urinary bladder. • Breakthrough pyelonephritis
• This one way valve prevents retrograde pas- • Intolerance or noncompliance with anti-
sage of urine from the urinary bladder into the biotic suppression
ureter. • Parental preference
• Failure of this uretrovesical junction one way – Relative indications:
valve will result in VUR. • Pubertal age
• Vesicoureteral reflux is divided into two types • High-grade (IV or V) VUR (Figs. 6.38
based on etiology. and 6.39)
• Primary VUR: • Failure to resolve
– This is secondary to a congenitally defi- • Increasing experience shows that a consider-
cient UVJ able number of children with VUR may
Figs. 6.35, 6.36, and 6.37 Micturating cystourethrograms showing primary VUR and secondary VUR associated with
posterior urethral valves
6.7 Vesicoureteral Reflux (VUR) 211
Figs. 6.38 and 6.39 Micturating cystourethrograms showing mild and severe VUR
demonstrate improved renal function on radi- • Surgical treatment:

ography, without surgical intervention. – Because the submucosal ureter tends to
• Nonoperative treatment mandates close fol- lengthen with age, the ratio of tunnel length
low-up care in patients with VUR. to ureteral diameter also increases, and the
• Nonoperative management of VUR includes: propensity for reflux may disappear.
– Antimicrobial suppression – Successful nonoperative management of
– Treatment of voiding dysfunction VUR requires preventing renal damage
– Regular imaging studies to assess renal from pyelonephritis and has involved the
growth, renal scarring, and possible resolu- use of continuous antibiotic prophylaxis
tion of pathology. and treating bowel or bladder dysfunction.
• The need for antibiotic prophylaxis in all – Dextranomer hyaluronic acid copolymer is
patients with VUR has been brought into a bulking agent for endoscopic treatment of
question. VUR.
• Current recommendations include low-dose – Endoscopic treatment results in reflux res-
antibiotic suppression in children younger olution or downgrading in most patients,
than 1 year with VUR and a history of febrile with long-term success rates of approxi-
UTI, based on greater morbidity from recur- mately 60–70 %.
rent UTI in this population. – Although not as effective as open ureteral
• Use of antibiotic prophylaxis in older children reimplantation, endoscopic correction of
with VUR should be made on an individualized VUR offers a minimally invasive, outpa-
basis; however, the use of prophylaxis would tient procedure with a low risk of
appear to be the most beneficial in those with complications.
grade 3 or greater reflux, girls, those with a sig- – In general, ureteral reimplantation has
nificant history of recurrent febrile UTIs, and/ excellent results (>95 % success rate).
or those with bowel or bladder dysfunction. Although the transvesical approach is
commonly used, the extravesical approach • Cases of high-grade VUR are less likely to spon-
(detrusorrhaphy) preserves the integrity of taneously resolve and more likely to put the kid-
the bladder lumen and does not require a ney at risk of scarring due to pyelonephritis.
ureteral anastomosis. Extravesical reim- • Prevention of infection is essential to mini-
plantation has been shown to decrease mize the risk of renal damage; therefore, con-
postoperative hematuria, minimize bladder tinuous antibiotic prophylaxis is usually used
spasms, reduce the need for urethral cathe- in children with high-grade VUR while await-
ter, and shorten hospital stay. Of note, tran- ing spontaneous resolution.
sient cases of urinary retention have been • Robotic-assisted ureteral reimplantation has
reported with bilateral extravesical ureteral gained popularity and will continue to evolve
reimplant. Although open ureteral reim- with time, although open ureteral reimplanta-
plantation remains the gold standard, mini- tion currently remains the criterion standard
mally invasive techniques (robotic assisted for surgical management of VUR.
ureteral reimplantation) have demonstrated • Antibiotic prophylaxis for all children with
comparable success rates. VUR remains controversial, although it is rec-
• Complications of ureteral reimplantation are ommended in children younger than 1 year
uncommon. with a history of febrile UTI or grade III reflux
• The most common technical complications or higher.
are ureteral obstruction, persistent reflux, and • Bowel and bladder dysfunction are often asso-
diverticula formation. ciated with VUR and increase the risk of
• Ureteral reimplantation for mega ureter repair pyelonephritis, so should be evaluated and
is a very safe, reproducible, and successful treated aggressively in children with VUR.
procedure.
• The major complications are the development
of ureteral obstruction (2–5 %) or VUR 6.8 Mega Ureter
(approximately 10 %).
• Ureteral obstruction is most likely the result of • The term mega ureter refers to an enlarged
ureteral ischemia and subsequent fibrosis of ureter.
an excisionally tapered segment. • A mega ureter is a wide ureter, greater than
• Initial management of this complication is per- 7 mm in diameter (Fig. 6.40).
cutaneous or endoscopic dilatation and stent- • Light microscopy of mega ureters demonstrates
ing of the stricture, but many such instances a predominance of circular smooth muscle;
ultimately require open surgical revision. muscle fiber hypoplasia and atrophy, with col-
• If postoperative VUR is encountered, a rea- lagen deposits separating the muscle cells; and
sonable treatment option is observation and mural fibrosis with scant muscle fibers.
antibiotic prophylaxis because many reflux • Electron microscopy of mega ureters demon-
cases resolve spontaneously. strates increased collagen deposition within
• In addition, VUR is more likely to recur fol- the adynamic segment.
lowing reimplantation in cases in which blad- • Megaureters may be classified into the follow-
der pressures are elevated (e.g. patients with ing four categories:
untreated neuropathic bladders or voiding – Obstructed
dysfunction). – Refluxing
• Treatment of bladder/bowel dysfunction is – Obstructed and refluxing
indicated, preferably prior to surgical inter- – Nonobstructed/nonrefluxing
vention of VUR. Careful assessment of void- • Each of these categories is further divided
ing symptoms and a low threshold for into:
urodynamic studies are crucial in the evalua- – Primary
tion of patients with recurrent VUR. – Secondary
6.8 Mega Ureter 213
that fails to effectively propagate urine

flow (Figs. 5.41 and 5.42).
• Secondary obstructed mega ureter:
– This occurs usually when ureteral dilatation
is the result of a functional ureteral obstruc-
tion associated with elevated bladder pres-
sures secondary to PUV or a neurogenic
bladder that impedes ureteral emptying.
• Primary refluxing mega ureter:
– This is associated with severe VUR that alters
ureteral efficiency by ureteral distention.
– The megaureter-megacystis syndrome is
an extreme form of the primary refluxing
mega ureters in which massive reflux pre-
vents effective bladder emptying because
urine is passed back and forth between the
ureters and bladder.
• Secondary refluxing mega ureter:
– This occurs secondary to PUV or neurogenic
bladder when elevated bladder pressures
cause decompensation of the uretrovesical
junction.
Fig. 6.40 Intravenous urography showing a right mega
• Primary nonrefluxing/nonobstructed mega
ureter secondary to uretero-vesical junction obstruction
ureter:
– This is diagnosed when no evidence of
obstruction or reflux can be demonstrated.
Classification of Mega Ureter
• Secondary nonrefluxing/nonobstructed mega
• Primary
ureter:
• Secondary
– This occurs secondary to diabetes insipi-
dus, in which high urinary flow rates may
Mega ureters are also classified into:
overwhelm the maximum transport
capacity of the ureter by peristalsis or as
• Obstructive
the result of ureteral atony accompanying a
• Reflexing
gram-negative UTI.
• Obstructed and refluxing
• Primary refluxing obstructed mega ureter:
• Nonobstructed/Nonrefluxing
– This occurs in the presence of an incompe-
tent VUJ that allows reflux through an ady-
namic distal segment.
• This is based on their etiology, either intrinsic • Indications for surgical interventions:
or extrinsic. – Increasing hydroureteronephrosis
• Bilateral involvement is present in about 20 % of – Decrease in renal function of involved
patients with primary obstructed mega ureters. kidney
• Primary obstructed mega ureter has a male-to- – Development of UTI or recurrent pain
female ratio of nearly 4:1. • Increasing experience shows that a consider-
• The left side is more often affected than the right. able number of children with mega ureters
• Primary obstructed mega ureter: without reflux or obstruction may demonstrate
– This is most commonly caused by an ady- improved renal function on radiography, with-
namic juxtavesical segment of the ureter out surgical intervention.
Figs. 6.41 and 6.42 Intravenous urography showing megaureter. Note the small caliber of the distal ureter
• Nonoperative treatment mandates close follow- • There have been reports of obstructive mega
up care in patients with nonobstructed/nonre- ureters treated successfully by endoscopic
fluxing mega ureters. dilation.
• Nonoperative management of nonobstructed • Complications of ureteral reimplantation are
primary mega ureter includes antimicrobial uncommon.
suppression, treatment of voiding dysfunc- • The most common technical complications
tion, and regular imaging studies to assess are ureteral obstruction, persistent reflux, and
renal growth, renal scarring, and possible res- diverticula formation.
olution of pathology. • Ureteral reimplantation for mega ureter repair
• Mega ureter secondary to severe VUR or is a very safe, reproducible, and successful
obstruction is usually managed with ureteral procedure.
reimplantation (Figs. 6.43, 6.44, 6.45, and 6.46). • The major complications are:
• Reimplantation techniques are similar to those – The development of ureteral obstruction
used for correcting primary VUR. (2–5 %)
• The mega ureter can be mobilized via an intra- – VUR (approximately 10 %).
vesical, extravesical, or combined approach. • Ureteral obstruction is most likely the result of
• Most mega ureters will require tapering. ureteral ischemia and subsequent fibrosis of
• The ureteral caliber can be reduced by excis- an excisionally tapered segment.
ing the distal redundant ureter (Hendren tech- • With respect to primary mega ureters, as in the
nique) or plication (Kalicinski technique, case of VUR, spontaneous resolution is
Starr technique) to achieve a satisfactory anti- common.
reflux mechanism. • In the case of the obstructed primary mega
• Occasionally, the function of the kidney ureter, spontaneous resolution is less likely to
drained by a mega ureter is severely impaired, occur; however, a study reported a 70 % spon-
and nephroureterectomy may be necessary. taneous regression.
Further Reading 215
Figs. 6.43 and 6.44 Clinical intraoperative photographs segment of the lower ureter. Note also the dilated ureter
showing megaureters secondary to a stenosed adynamic proximal to the stenotic segment
lower ureteric segment. Note the diameter of the stenosed
Figs. 6.45 and 6.46 Clinical intraoperative photographs segment of the lower ureter. Note also the dilated ureter
showing megaureters secondary to a stenosed adynamic proximal to the stenotic segment
lower ureteric segment. Note the diameter of the stenosed
4. Bansal D, Cost NG, Bean CM, Noh PH. Pediatric

Further Reading laparo-endoscopic single site partial nephrectomy:
feasibility in infants and small children for upper
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Congenital Megaureter
7
7.1 Introduction • The left side is more commonly affected than

the right (1.6–4.5 times).
• The term megaureter refers to an enlarged • Primary obstructed megaureter is more com-
dilated ureter (Fig. 7.1). mon in males with male-to-female ration of
• In children, any ureter greater than 7 mm in about 4:1.
diameter is considered a megaureter. • Congenital primary megaureter is an idiopathic
• The megaureter is divided into two main condition in which the bladder and bladder out-
groups depending on etiology: let are normal but the ureter is dilated.
– Primary megaureter:
• This results from a functional or
anatomical abnormality involving the
ureterovesical junction (Fig. 7.2).
– Secondary megaureter:
• This results from abnormalities that
involve the bladder or urethra including:
– Myelomeningocele/neurogenic
bladder
– Severe urethral stricture
– Posterior urethral valves
• Primary megaureter is further sub classified
according to the presence or absence of reflux
and obstruction.
• Megaureter is divided into four types:
– Refluxing megaureter
– Obstructed megaureter
– Refluxing/obstructed megaureter
– Non-refluxing/ non-obstructed megureter
• Each of these types is further subdivided into
primary or secondary:
– This is based on either intrinsic or extrinsic
causes for their appearance. Fig. 7.1 Intravenous urography showing a right mega-
• Bilateral involvement is present in about 20 % ureter. Note the markedly dilated ureter causing back
of patients with primary obstructed megaureter. pressure on the kidney

218 7 Congenital Megaureter
DILATED – Abdominal and flank pain

URETER
– Microscopic hematuria is frequent and
may occur without infection.
– The presence of microscopic hematuria
may indicate calculus formation.
– These patients rarely present with signs of
renal failure.
NARROW DISTAL • Vesicoureteric reflux disease (VUR): although
URETERIC SEGMENT
actually a cause of primary congenital mega-
ureter it is usually considered separately as
prognosis and treatment, depending on degree
of reflux, is different
• Causes of secondary megaureter include
Fig. 7.2 A clinical intraoperative photograph showing a (Figs. 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 7.10,
primary megaureter. Note the small narrowed distal ure- 7.11, 7.12, 7.13, and 7.14):
teric segment which is aperistalitic
– Posterior urethral valve: This is often
associated with bilateral hydroureter/
• Primary megaureter is the second most com- hydronephrosis
mon cause of neonatal hydronephrosis. – Ureteral diverticulum
• The majority of cases are non-refluxing and – Urolithiasis
unobstructed. – Urotrocele
• The incidence of obstructed megaureter is 1 in – Duplex collecting system with reflux into
10,000 live newborns. lower pole moiety
• Most primary megaureter in neonates is non- – Myelomeningocele/neurogenic bladder
refluxing and unobstructed. – Severe urethral stricture
– The etiology of this is unknown • Primary megaureter is a common cause of
– It may be due to high fetal urine outflow obstructive uropathy among neonates and
– It may be caused by changes in the ure- young children.
ter pre- and postnatal or transient ana- • It is estimated that vesico-ureteric junction
tomical obstructions that improve with obstruction account for 23 % of neonates diag-
postnatal development, such as ureteral nosed with obstructive uropathy.
folds. • Children presenting before 1 year old are
• In unilateral primary megaureter the contra- more likely to have bilateral Primary mega-
lateral kidney is absent or dysplastic in ureter than are older patients.
10–15 % of patients. • The condition is not known to be hereditary,
• About 50 % of primary megaureter cases are but families with more than one member with
asymptomatic and are discovered on routine PM have been described.
antenatal ultrasound.
• Most asymptomatic patients have unobstructed
primary megaureter. 7.2 Classification
• Symptomatic primary megaureter present
with: • The term ‘megaureter’ could be applied to any
– Urinary tract infections dilated (mega) ureter.
– Hydronephrosis • In general use, the term megaureter is not
– Fever applied to a hydroureter caused by overt
Figs. 7.3 and 7.4 Micturating cystourethrograms showing posterior urethral valves and associated vesicoureteral
reflux
neuropathic bladder or typical bladder neck • In primary megaureter the cause is

obstruction. idiopathic.
• Megaureter is usually reserved for conditions • Secondary megaureter may be caused by:
in which the bladder and bladder outlet are – Urethral obstruction
normal but the ureter is dilated. – Bladder outlet obstruction
• Many classifications were proposed for – Neurogenic bladder
megaureter. – Polyuria
• The international classification of Smith et al. – Infection
is the most comprehensive classification. • A more practical classification of megaureter
– Obstructed was given by King as:
– Refluxing – Refluxing
– Unobstructed – Obstructed
– None refluxing – Not refluxing
• Each of these categories is subdivided into a – Not obstructed
primary and secondary group. – Refluxing and obstructed
Figs. 7.5, 7.6, and 7.7 CT-urography showing duplex system and bilateral hydroureteronephrosis. Note the dilated
megaureters
DYSPLASTIC URETROCELE
KIDNEY
MEGAURETER
Figs. 7.8, 7.9, and 7.10 Pelvic ultrasound and intraoperative photograph showing uretrocele. Note the markedly
dilated ureter
• Primary megaureter usually includes: urine from the ureter into the urinary
– Obstructed primary megaureter bladder.
– Unobstructed primary megaureter • Secondary obstructed megaureter:
• Secondary megaureter is caused by a variety – This occurs usually when ureteral dilata-
of urological disorders. tion is the result of a functional ureteral
• Primary obstructed megaureter: obstruction associated with elevated
– This is most commonly caused by an bladder pressures secondary to PUV or a
adynamic juxtavesical segment of the neurogenic bladder that impedes ureteral
ureter that fails to effectively propagate emptying.
• Primary refluxing megaureter:

Classification of Megaureter – This is associated with severe VUR that
• The international classification of Smith alters the uretero-vesical junction leading
et al. is the most comprehensive to dilatation of the ureter.
classification. – The megaureter-megacystis syndrome is
– Obstructed an extreme form of primary refluxing
– Refluxing megaureters.
– Unobstructed • Secondary refluxing megaureter:
– None refluxing – This occurs secondary to posterior urethral
• Each of these categories is subdivided valve and neurogenic bladder.
into a primary and secondary group. – Elevated urinary bladder pressure causes
– Primary obstructed megaureter decompensation of the one-way valve at
– Secondary obstructed megaureter the uretero-vesical junction.
– Primary refluxing megaureter
– Secondary refluxing megaureter Class Primary Secondary
– Primary nonrefluxing/nonobstructing Obstructed Intrinsic Infravesical
megaureter ureteric obstruction
– Secondary nonrefluxing/nonobstruct- obstruction (an (elevated bladder
ing megaureter adynamic pressure secondary
juxtavesical to PUV or a
– Primary refluxing/obstructed megaureter segment of the neurogenic bladder
ureter) that impedes
ureteral emptying)
Refluxing Reflux is the Associated with
only bladder outlet
abnormality obstruction or
(severe VUR neurogenic bladder
that alters the (Elevated urinary
uretero-vesical bladder pressure
junction) causes
decompensation of
the uretero-vesical
junction
Non- Idiopathic Polyuria (diabetes
refluxing/ ureteric insipidus) or
unobstructed dilatation gram – ve UTI
(No obstruction
or reflux)
• Primary nonrefluxing/nonobstructed
megaureter:
– This is diagnosed when no evidence of
obstruction or reflux can be demonstrated.
• Secondary nonrefluxing/nonobstructed
megaureter:
– This occurs secondary to diabetes insipi-
Fig. 7.11 Micturating cystourethrogram showing mas- dus, in which high urinary flow rates may
sively dilated ureter overwhelm the maximum transport
7.3 Etiology and Pathophysiology 223
capacity of the ureter by peristalsis or as 7.3 Etiology

the result of ureteral atony that accom- and Pathophysiology
pany a gram-negative urinary tract
infection. • Primary obstructive megaureter:
• Primary refluxing obstructed megureter: – It is a common cause of obstructive uropa-
– This occurs in the presence of an incompe- thy in children.
tent VUJ that allows reflux through an ady- – There is a general agreement that there is
namic distal segment. no true narrowing at the VUJ.
Figs. 7.12, 7.13, and 7.14 Micturating cystourethrogram showing severe bilateral reflux and megaureters. Note the
absence of posterior urethral valve
– This is a functional obstruction secondary – This was supported by the finding of TGF-
to a distal adynamic juxtavesical segment β in the aperistalitic segment but not in the
0.5–4 cm long that is unable to transport dilated ureter and since TGF-β is not nor-
urine at acceptable rates. mally found in the ureter, a developmental
– This leads to proximal ureteric dilatation. abnormality may explain its pathogenesis.
– The exact etiology of this aperistatic seg- – This also may explain the frequent sponta-
ment is not known. neous resolution of primary megaureter
– Several etiological theories have been pro- within the first 2 years of postnatal life,
posed including: where the circular muscular pattern, which
• Excessive collagen deposition. is typical of the fetal ureter, changes pro-
• Increased matrix deposition alters cell- gressively into the double muscle layers of
to-cell junctions and disrupts myoelec- the full-term infant.
trical propagation and peristalsis. – The degree of ureteric dilatation that results
• Segmental changes of ureter muscle depends on the amount of urine forced to
cells, where there is atrophy of the inner accumulate proximally.
longitudinal layer that conducts the per- – This in turn is determined by the degree of
istaltic waves and hypertrophy of the distal obstruction and urinary output.
outer circular layer that causes – The dilated ureter provide a larger reservoir
obstruction. and hence less likely to transmit damaging
• Thick circumferential periureteral tis- pressure to the kidney.
sues devoid of muscle. • Primary refluxing megaureter:
• A bulky peri-ureteric sheath – Primary refluxing megaureter results from
• A thick sleeve of muscle forming a con- an abnormal vesico-ureteric junction,
tinuous layer surrounding the muscle which impedes the normal anti-reflux
bundles of the terminal ureter. The mus- mechanisms.
cle forming this outer layer is distinct in – This can be due to:
its histological appearance and arrange- • A short intravesical ureter
ment from the muscle bundles which • Congenital paraureteric diverticulum
form the ureteric muscle of the • Ureterocoele with or without associated
VUJ. Furthermore, this muscle layer is duplicated collecting system
very densely innervated by nonadrener- • Other derangement of the vesico-
gic (immunoreactive to dopamine beta- ureteric junction
hydroxylase) nerves when compared – It may be associated with megacystis
with the smooth muscle coat of the ure- megaureter syndrome and prune belly
ter. This dense nonadrenergic innerva- syndrome.
tion of this muscle collar might cause it – The marked increase in collagen and sig-
to constrict inappropriately, impeding nificant decrease in smooth muscle could
urinary flow, and ultimately lead to the be a major contributing factor in the patho-
development of megaureter. genesis of refluxing primary megaureter.
• The altered peristalsis prevents the free – There are a few patients with refluxing pri-
outflow of urine and functional obstruc- mary megaureter who have the megacystis-
tion results. megaureter association, with the
– The fact that the distal ureter is the last por- characteristics of:
tion of the ureter to develop its muscular • Bilateral hydroureteronephrosis
coat and that early muscular differentiation • A large thin-walled urinary bladder
is primarily of the circular muscle may • Bilateral high-grade VUR
explain why the aperistalitic segment affect – Another special group of patients with dilated
only the distal segment of the ureter. ureters are those with prune-belly syndrome,
in which the dilated ureters may be caused by 7.4 Clinical Presentation

reflux or VUJ obstruction, or maybe not
refluxing and unobstructed, and categorized • The widespread use of obstetrical US with
according to these characteristics. concomitant fetal screening resulted in an
– A dysgenetic distal ureteric segment that increase in the prenatal diagnosis of congeni-
not only fails to cope within the intramural tal uropathies, including megaureter.
tunnel but also has ineffective peristalsis is • Currently, about half of the cases of congenital
implicated in its pathogenesis. megaureter are asymptomatic and discovered
• Non-refluxing unobstructed primary megaureter: on prenatal US.
– This is thought to be the most common • Symptomatic patients commonly present with
cause of primary megaureter in neonates, UTI, fever and abdominal pain.
and even though the vesicoureteric junc- • Microscopic hematuria is frequent and may
tion is normal, with no evidence of reflux occur in the absence of urinary tract infection.
or obstruction the ureter is enlarged. This is presumably caused by the disruption of
– Most primary megaureter in neonates fall mucosal vessels of the ureter secondary to
into this category. ureteric distension.
– There is neither reflux nor stenosis of the • Hematuria may also be a sign of calculus for-
juxtavesical ureter, but the ureter is dilated mation secondary to urinary stasis.
beginning at a point just above the bladder. • It is not unusual for the dilated asymptomatic
– The cause of this phenomenon is unknown. ureter to be noted at the time of abdominal
– Several theories were proposed: surgery for other reasons.
• Fetal urine production is four to six • Rarely, these patients present late with signs
times greater before than after delivery. of renal failure.
This is because of differences in renal
vascular resistance, GFR and concen-
trating ability.
• This high outflow might contribute to ure- 7.5 Investigations and Diagnosis
teric dilatation in the absence of function-
ally significant obstruction, as is • The diagnosis of megaureter is based on clini-
occasionally seen with diabetes insipidus. cal presentation and ultrasound before and
• Another contributing factor appears to after birth.
be increased compliance of the fetal • The antenatal diagnosis of megaureter is based
ureter because of differences in the on ultrasound showing hydronephrosis.
deposition of type III collagen, elastin • The diagnosis is confirmed by postnatal
and other extracellular matrix proteins. ultrasound.
• Partial or transient anatomical or func- • Grey-scale ultrasound:
tional obstructions that spontaneously – Grey-scale ultrasound is the initial study
improve with postnatal development could obtained in any child in whom a urinary
contribute to proximal ureteric dilatation. abnormality is suspected.
• Persistent fetal ureteric folds or delays – It provides useful anatomical detail of the
in the development of normal ureteric renal parenchyma, collecting system, ure-
peristalsis may be responsible for such ter and bladder.
transient obstructions. – Ultrasound offers a baseline of the degree
• Primary megaureter is not known to be heredi- of hydroureteronephrosis that can be used
tary, but families with more than one affected in serial follow-up.
member have been described. • The finding of a ureter more than 7 mm in
• Primary megaureter may be associated with diameter confirm the diagnosis of a
renal agenesis, megacalycosis and urolithiasis. megaureter.
Figs. 7.15, 7.16, and 7.17 Abdominal and pelvic ultrasound showing primary megaureter. Note the markedly dilated
ureter
– The distal ureter above this narrowed seg-

ment is most dilated.
– There is associated hydronephrosis.
– Active peristaltic waves can be seen on
ultrasound.
• The primary nature of megaureter must be
confirmed and the secondary causes of mega-
ureter must be excluded.
• Causes of secondary megaureter include:
– Polyuria (diabetes insipidus)
– Infection
– Bladder outlet obstruction
– Neuropathic bladder
Fig. 7.18 A micturating cystourethrogram of the same – Non-neurogenic voiding dysfunction
patient showing no vesicoureteral reflux – Infravesical obstruction or extrinsic lesions
such as posterior urethral valve and severe
urethral stricture.
• In obstructive primary megaureter (Figs. 7.15, • Doppler ultrasonography:
7.16, 7.17, and 7.18): – Doppler ultrasonography with a measure-
– The ureter tapers to a short segment of nor- ment of renal resistive index (RI) was
mal caliber or narrowed distal ureter, usually recently introduced as a noninvasive method
just above the vesicoureteric junction (VUJ). of diagnosing obstructive uropathy.
Figs. 7.19 and 7.20 Intravenous urography showing megaureter. Note the dilated ureter and back pressure on the
kidney. Note also the tapered lower ureter in the second picture
– It has been shown that the RI is age- • The diagnosis is confirmed by intravenous
dependent and is commonly >0.70 in urography (IVU) and radioisotope renography.
healthy children in the first year of life. • Intravenous urography (IVU) (Figs. 7.19 and
– A normal RI exclude obstruction in the 7.20):
presence of a dilated collecting system. – The anatomical detail provided by IVU is
– An RI threshold of 0.70 gave a sensitivity useful when the level of obstruction cannot
of 82 %, a specificity of 63 % and an overall be defined.
accuracy of 76 % in children with obstruc- – IVU usually shows the pathognomonic
tive uropathy. configuration of a dilated distal ureteric
– Several methods have been used to increase spindle, a less dilated proximal ureter and a
the diagnostic accuracy of RI. dilated or relatively normal-appearing
– The infusion of normal saline and adminis- renal pelvis.
tration of frusemide significantly decreased – Caliectasis is either absent or mild.
the RI of unobstructed kidneys and – IVU is currently rarely used as an initial step
increased the RI of obstructed units. in the diagnosis of primary megaureter.
– The calculation of the difference between – This is especially in neonates because of
the RI of obstructed and unobstructed kid- renal immaturity and bowel gas.
neys (ΔRI) strengthens the diagnosis. – IVU should not be used before the age of
– Values of ΔRI of >0.06–0.10 are diagnostic 3–4 weeks and images taken 1 and 2 h after
of obstruction. injection with contrast medium should be
– Recent reports showed a good correlation obtained.
between the RI and DR. Therefore, the RI • Radioisotope renography (Figs. 7.21 and
could be used for monitoring the dilated 7.22):
collecting systems under observation, – A renogram provides anatomical informa-
obviating the need for frequent radioiso- tion together with objective reproducible
tope scanning. variables of both function and obstruction.
Figs. 7.21 and 7.22 Isotope renogram showing a dilated left ureter (megaureter) with evidence of obstruction
– The most commonly used radionuclides – Measuring individual renal function to

are 99mTc-DTPA and -MAG3. detect a decrease in function has been used
– To assess obstruction, the diuretic reno- by some to show the presence of
gram is used to detect the pattern of the obstruction.
frusemide washout curve and the half-time – The critical value of individual renal func-
drainage (T1/2). tion below which obstruction is considered
– In the standard diuretic renogram, has varied among different studies.
frusemide is given 20 min after the injec- – Values of <30 %, <35 %, or <40 % have
tion of tracer. To decrease the false-positive been suggested (normal 50 ± 5 %).
results this technique was modified and – The failure of an expected improvement in
frusemide is given 15 min before the injec- renal function on further sequential
tion of tracer. This is called F-15 instead of radionuclide studies could be an indicator
the usual F+20 technique. of the presence of obstruction.
– Heyman and Duckett described the extrac- • VUR is diagnosed using voiding cystoure-
tion factor (EF) as an estimate of single- thrography (VCUG) (Figs. 7.23, 7.24, 7.25,
kidney function in children during routine 7.26, and 7.27).
radionuclide renography with 99mTc-DTPA. – Once ureteric dilatation is detected by US,
– The EF is defined as the percentage uptake VCUG is used to exclude reflux, and assess
of radionuclide by the kidneys 2–3 min the quality of the bladder and urethra.
after injection with isotope. – In refluxing primary megaureter, vesico-
– The normal mean EF in the new-born is 1.5 % ureteric reflux is demonstrated.
by each kidney, with an increase to 2.5 % – In non-refluxing unobstructed primary
occurring by the end of the first year of life. megaureter:
– The correlation coefficient of the EF with • There is absent or only a minor degree
GFR is 0.92. of hydronephrosis.
– If renal function is normal by EF and/or equal • Although rare, congenital megaureter
to the contralateral undilated renal unit, the may co-exist with congenital megacaly-
dilatation seen does not represent a function- ces, making assessment of hydrone-
ally significant obstructive uropathy. phrosis more difficult.
Figs. 7.23, 7.24, 7.25, 7.26, and 7.27 Micturating cystourethrograms, isotope renography and micturating cystoure-
throgram of a patient with severe bilateral vesicoureteric reflux but no posterior urethral valve
Figs. 7.23, 7.24, 7.25, 7.26, and 7.27 (continued)

7.6 Treatment and Prognosis 231
– Reflux and obstruction may coexist in a – Follow-up regular imaging studies to

small proportion of patients; in such assess renal growth, renal scarring, and
instances, the reflux is often the most obvi- possible resolution of pathology.
ous finding and concomitant obstruction • Current recommendations for antibiotic pro-
may not be considered unless the possibil- phylaxis in all patients with VUR include:
ity of a dual lesion is considered. – Antibiotic prophylaxis for children younger
– If a delayed film is obtained after the than 1 year with VUR and a history of
VCUG, poor drainage of one or both upper febrile UTI, based on greater morbidity
tracts may suggest associated VUJ from recurrent UTI in this population.
obstruction. – The use of antibiotic prophylaxis in older
– This can be confirmed or excluded by fur- children with VUR should be made on an
ther evaluation. individualized basis.
– The final and most difficult step in the diag- – The use of antibiotic prophylaxis is most
nosis is to differentiate between an beneficial in:
obstructed and unobstructed megaureter. • Those with grade 3 or greater VUR
– Tests such as renal scintigraphy, Doppler • Girls
ultrasonography (DUS) and pressure-flow • Those with a significant history of
studies (the Whitaker test) are useful recurrent febrile UTIs
investigations. • Those with bowel or bladder
• The diagnosis in most cases is only possible dysfunction
by repeated investigations and comparivng • Usually primary megaureter is asymptomatic
changes of the variables during a longer and requiring no treatment.
follow-up. • If complications occur or the degree of
• The Whitaker test: obstruction is marked then re-implantation
– The Whitaker test is currently rarely used following resection of the aganglionic seg-
in the diagnosis of children with ment may be performed.
megaureter. • Megaureter secondary to severe VUR or
– It is invasive, does not measure function, obstruction is usually managed with ureteral
submits the collecting system to unphysio- reimplantation.
logical rates of flow and has a variable cor- • Reimplantation techniques are similar to those
relation with functional studies such as the used for correcting primary VUR.
diuretic renogram. • The megaureter can be mobilized via an
intravesical, extravesical, or combined
approach.
7.6 Treatment and Prognosis • Most megaureters will require tapering.
• The ureteral caliber can be reduced by:
• Increasing reports show that a considerable – Excising the distal redundant ureter
number of children with VUR or megaureters (Hendren technique)
without reflux or obstruction may demonstrate – Plication (Kalicinski technique, Starr
improved renal function on radiography technique)
follow-ups, without surgical intervention. • Occasionally, the function of the kidney
• Nonoperative treatment however, requires drained by a megaureter is severely impaired,
close follow-up of patients with VUR or non- and nephroureterectomy may be necessary.
obstructed/non-refluxing megaureters. • There have been reports of obstructive mega-
• Nonoperative management of VUR and non- ureters treated successfully by endoscopic
obstructed primary megaureter includes: dilation.
– Antimicrobial prophylaxis • The treatment of primary megureter depends
– Treatment of voiding dysfunction on the type:
• Refluxing primary megaureter: – During the past 10 years there has been an
– With the advent of antenatal ultrasound the increasing trend towards conservative
management of refluxing primary mega- management.
ureters changed in the past few years. – In this approach of conservative
– The previous recommendation for surgery management:
in newborns and infants with grades 4 and • The patients are closely monitored
5 reflux is obsolete. including their symptoms
– Medical management is appropriate during • Imaging follow-up
infancy and is continued if there is a trend • Antibiotic prophylaxis
to resolution. – The frequency of imaging decreases as the
– Surgery is recommended for persistent urinary tract dilatation stabilizes.
high-grade reflux in older children. – Renal function is best assessed by renal
• Nonrefluxing unobstructed primary megaureter: scintigraphy
– Most patients who present with primary – Antibiotic prophylaxis must be begun rou-
megaureter, particularly older children, tinely soon after delivery in infants with
clearly have the unobstructed variety. prenatally detected hydroureteronephrosis.
– Most of these patients remain asymptom- – Prophylaxis is continued after confirming
atic without surgery, and expectant man- the diagnosis of an obstructed primary
agement results in an improvement in the megaureter.
degree of urinary tract dilatation and no – When surgical repair is undertaken prophy-
deterioration of renal function. laxis is continued until the obstruction is
– This requires regular follow-up with antibi- relieved and no reflux is detected.
otic prophylaxis for urinary tract infections. – The commonly used antibiotics for pro-
• Obstructed primary megaureter: phylaxis are:
– Many cases of primary megaureter diag- • Amoxicillin (15 mg/kg) once a day for
nosed antenatally resolve spontaneously infants <2 months
within the first 2 years of life, with the mat- • Trimethoprim (2 mg/kg) once a day for
uration of the urinary tract. infants and children
– These are called ‘primary dilated megaure- – Surgery is indicated in cases of:
ter’ by some authors to differentiate them • Significant impairment to urine flow
from the real obstructive ones. • Persistent pain
– The presence of significant obstruction is • Pyelonephritis
an indication for early surgical correction • Calculi
to preserve renal function. • A decrease in renal function
– The goals of early surgery are: • Principles of surgical treatment (Figs. 7.28,
• To minimize renal damage from 7.29, 7.30, 7.31, and 7.32):
obstruction – The ureter is mobilized as for reimplanta-
• To maximize the growth potential of the tion for VUR.
affected kidney – Resection of the distal ureter only is rarely
• To prevent complications of primary sufficient to permit reimplantation.
megaureter, especially infection and – Reduction of the caliber of the distal ureter
stone formation. is necessary.
– However, presently there is no ideal – Two methods can be used to remodel
method for assessing urinary tract obstruc- megaureters.
tion, particularly in neonates and infants. • Hendren technique: Excision of the
– Therefore, the therapeutic recommenda- distal severely dilated and redundant
tions for neonates with obstructed primary ureter or those that are markedly
megaureter remain controversial. thickened.
Figs. 7.28, 7.29, 7.30, 7.31, and 7.32 Clinical intraoperative photographs showing reimplantation of primary mega-
ureters. Note the distal stenosed aperistalitic segment ( ) and the proximally dilated ureter ( )
• Plication (Kalicinski technique, Starr – Nonetheless, the frequency of postopera-

technique): Plication of the distal ureter tive reflux is no different between these
is used when there is less dilatation, but methods.
may produce a bulky and stiff ureteric – In the past, reduction of the caliber of the
segment. distal and mid ureter was done, but
currently reduction is limited to a section • Careful assessment of voiding symptoms and

of ureter necessary to achieve an adequate a low threshold for urodynamic studies are
length of intravesical tunnel. crucial in the evaluation of patients with recur-
– Remodelled megaureters have generally rent VUR.
been reimplanted using: • A renal ultrasound should be obtained follow-
• The standard Cohen cross-trigonal ing surgical correction of VUR to assess for
reimplantation obstruction.
• The Leadbetter-type reimplantation • Because of the very high success rate of open
• The extravesical submucosal tunnel ureteral reimplantation, a postoperative
repairs VCUG is performed only in select cases.
• The extravesical seromuscular tunnel • Concomitant ipsilateral PUJ obstruction can
repair be seen in infants with obstructive primary
megaureter.
– The preoperative diagnosis of both patho-
7.7 Complications logical conditions may be difficult.
– When PUJ obstruction is present, the ipsi-
• Ureteral reimplantation for megaureter repair lateral ureter is seldom seen on IVU.
is a very safe, reproducible, and successful – The diagnosis is not made until a retro-
procedure. grade ureterogram is taken when the child
• The success in reimplanting remodelled is under anaesthesia for a pyeloplasty or
megaureters, regardless of technique, is not as when the ureter is seen to be dilated at the
high as with undilated ureters. time of the pyeloplasty.
• Furthermore, in the neonatal period the com- – A preoperative renal scan is more helpful
plication rate is higher for reimplantation of a in this regard, as the obstructed ureter usu-
dilated ureter, especially into a small bladder. ally fills and is visualized as the obstructed
• The reported rate of reoperation for reflux or pelvis drains.
obstruction is about 12 %.
• The major complications are:
– The development of ureteral obstruction
(2–5 %) Further Reading
– VUR (approximately 10 %)
– Diverticular formation 1. Anderson CB, Tanaka ST, Pope 4th JC, Adams MC,
– Ureteral obstruction is most likely the result Brock 3rd JW, Thomas JC. Acute pain crisis as a pre-
sentation of primary megaureter in children. J Pediatr
of ureteral ischemia and subsequent fibrosis
Urol. 2011;8:254–7.
of an excisionally tapered segment. 2. Baskin LS, Zderic SA, Snyder HM, Duckett JW.
– Initial management of this complication is Primary dilated megaureter: long-term followup.
percutaneous or endoscopic dilatation and J Urol. 1994;152(2 Pt 2):618–21.
3. Baskin LS, Zderic SA, Snyder HM, Duckett JW.
stenting of the stricture, but many such
Primary dilated megaureter: long-term followup.
instances ultimately require open surgical J Urol. 1994;152:618.
revision. 4. Cooper CS. Diagnosis and management of vesicoure-
– If postoperative VUR is encountered, a rea- teral reflux in children. Nat Rev Urol. 2009;6(9):
481–9.
sonable treatment option is observation and
5. DeFoor W, Minevich E, Reddy P, Polsky E,
antibiotic prophylaxis because many reflux McGregor A, Wacksman J. Results of tapered ure-
cases resolve spontaneously. teral reimplantation for primary megaureter: extra-
• VUR is more likely to recur following reim- vesical versus intravesical approach. J Urol. 2004;
172(4 Pt 2):1640–3; discussion 1643.
plantation in cases in which bladder pressures
6. Di Renzo D, Aguiar L, Cascini V, et al. Long-term
are elevated (e.g. patients with untreated neu- follow-up of primary non-refluxing megaureter.
ropathic bladders or voiding dysfunction). J Urol. 2013;190:1021.
Further Reading 235
7. Farrugia MK, Hitchcock R, Radford A, et al. British ter in neonate and infant. J Urol. 2005;173(4):1357–60;
Association of Paediatric Urologists consensus state- discussion 1360.
ment on the management of the primary obstructive 13. Liu HY, Dhillon HK, Yeung CK, et al. Clinical out-
megaureter. J Pediatr Urol. 2014;10:26. come and management of prenatally diagnosed pri-
8. Fretz PC, Austin JC, Cooper CS, Hawtrey CE. Long- mary megaureters. J Urol. 1994;152:614.
term outcome analysis of Starr plication for primary 14. Massad C, Megaureter SE, Gonzales ET, Bauer SB,
obstructive megaureters. J Urol. 2004;172(2):703–5. editors. Pediatric urology practice. Philadelphia:
9. García-Aparicio L, Rodo J, Krauel L, et al. High pres- Lippincott Williams & Wilkins; 1999. p. 205.
sure balloon dilation of the ureterovesical junction – 15. McLellan DL, Retik AB, Bauer SB, et al. Rate and
first line approach to treat primary obstructive predictors of spontaneous resolution of prenatally
megaureter? J Urol. 2012;187:1834. diagnosed primary non-refluxing megaureter. J Urol.
10. Gimpel C, Masioniene L, Djakovic N, Schenk JP, 2002;168:2177.
Haberkorn U, Tönshoff B. Complications and long- 16. Renjen P, Bellah R, Hellinger JC, Darge K. Pediatric
term outcome of primary obstructive megaureter in urologic advanced imaging: techniques and applica-
childhood. Pediatr Nephrol. 2010;25(9):1679–86. tions. Urol Clin N Am. 2010;37(2):307–18.
11. Gimpel C, Masioniene L, Djakovic N, et al. 17. Shokeir AA, Nijman RJ. Primary megaureter: current
Complications and long-term outcome of primary trends in diagnosis and treatment. BJU Int. 2000;86(7):
obstructive megaureter in childhood. Pediatr Nephrol. 861–8.
2010;25:1679. 18. Shukla AR, Cooper J, Patel RP, et al. Prenatally
12. Lee SD, Akbal C, Kaefer M. Refluxing ureteral reim- detected primary megaureter: a role for extended fol-
plant as temporary treatment of obstructive megaure- lowup. J Urol. 2005;173(4):1353–6.
Vesicoureteral Reflux (VUR)
in Children 8
8.1 Introduction • This frequency decreases to 15 % by the age

of 12 years.
• Normally urine travels antegrade in one direc- • VUR is more commonly diagnosed in males
tion from the kidneys to the bladder via the antenatally, but in later life there is a definite
ureters to the urinary bladder. female preponderance with 85 % of VUR
• Backward or retrograde flow of urine from the cases being diagnosed in females.
urinary bladder to the ureters or kidneys is • Overall prevalence of vesicoureteral reflux is
prevented by a one way valve at the uretero- unknown because many children are
vesical junction. asymptomatic.
• The valve is formed by the oblique entrance of • A frequency of 1–2 % of VUR was reported
the distal ureter through the wall of the blad- among healthy children.
der. This creates a tunnel of about 1–2 cm into
the wall of the urinary bladder.
• This tunnel is compressed as the bladder fills
preventing backflow of urine.
• Vesicoureteral reflux (VUR) is a retrograde
flow of urine from the bladder into the ureters/
kidneys (Fig. 8.1).
• VUR occurs if the submucosal ureteric tunnel
is short making the valve defective.
• VUR is one of the common conditions in
infants and children.
• It has been estimated that 10 % of the popula-
tion have some degree of VUR.
• VUR is more common among younger chil-
dren because of the relative shortness of the
submucosal ureteric tunnel.
• This susceptibility decreases as the child
grows. This is as a result of growth and
increase in the length of the ureteric tunnel.
• It has been estimated that in children under the
age of 1 year with a urinary tract infection, Fig. 8.1 A micturating cystourethrogram showing sever
70 % of them will have VUR. bilateral vesicoureteral reflux

238 8 Vesicoureteral Reflux (VUR) in Children
• The prevalence of VUR is higher among chil- • It was estimated that among patients who pre-
dren with UTIs ranging from 15 to 70 %, sented with UTI:
depending on age. – The prevalence of VUR was 70 % in
• Approximately one third of patients diag- patients younger than 1 year
nosed prenatally with hydronephrosis on – The prevalence of VUR was 25 % in
ultrasonography, were found postnatally to patients aged 4 years
have VUR. – The prevalence of VUR was 15 % in those
• The incidence of reflux clearly is influenced aged 12 years
by genetic factors, although the specific modes – The prevalence of VUR was 5.2 % in adult
of inheritance is not defined. patients.
– Siblings of children with vesicoureteral • VUR is more prevalent in male newborns, but
reflux have a 25–33 % risk of also having VUR seems to be five to six times more com-
VUR. mon in females older than 1 year than in
– Offspring of parents with VUR have a 66 % males.
risk of also having VUR. • The incidence decreases as patient age
– This is higher in female offspring than increases.
male offspring. • Approximately three-quarters of children
• There are two distinct presentations of VUR: being treated for reflux are girls.
– Hydronephrosis, often prenatally identified • The diagnosis of VUR depends on clinical
using ultrasonography. suspicion and radiological investigations. The
– Clinical urinary tract infection. indications for radiological evaluation after
• VUR can occur at any age but the average age the first attack of urinary tract infection
at diagnosis of VUR is 2–3 years. include:
• It was suggested that early diagnosis of chil- – All children younger than 5 years.
dren with VUR may prevent episodes of UTI – Children of any age with febrile urinary
and renal scarring. tract infection.
• Others feel that screening asymptomatic chil- – Boys of any age with urinary tract
dren will result in overtreatment of clinically infection.
insignificant VUR. • In patients with VUR, there is a close correla-
• VUR is more common in white children than tion between the frequency of urinary tract
in those of other races. infection and the severity of VUR
• VUR is less common in black children. nephropathy.
• VUR is ten times as common in white chil- • VUR nephropathy is considered the most
dren as in black children. common cause of childhood hypertension
• UTIs are known to be more common in girls which is caused by increased renin secretion
than boys. as a result of renal scarring (Figs. 8.2, 8.3, 8.4,
• Among all children with UTIs, boys are more and 8.5).
likely to have vesicoureteral reflux than girls • The most devastating complication of VUR
(29 % of males vs 14 % of females). nephropathy is renal failure.
• Boys also tend to have higher grades of vesi- • Vesicoureteral reflux can be primary or
coureteral reflux diagnosed at younger ages. secondary.
• Vesicoureteral reflux is more likely to sponta- – Primary vesicoureteral reflux results
neously resolve in boys when compared to from a defect in the “flap valve” effect
girls. that normally prevents urine from flow-
• VUR is more common among infants and pro- ing backward from the bladder into the
gressively resolves in a substantial proportion ureters.
of children. – Secondary vesicoureteral reflux results
• The prevalence of VUR decreases as children from defective micturation secondary to
age. obstruction in the urethra such as posterior
8.1 Introduction 239
Figs. 8.2 and 8.3 Abdominal ultrasound showing atrophic left kidney secondary to VUR
Hydronephrosis Diagnosed Prenatally

• 50 % are transient and resolve
spontaneously.
• 15 % have hydronephrosis that persists
but is not associated with urinary tract
obstruction (non-refluxing, non-
obstructive hydronephrosis).
• 35 % have a definite pathological cause
for hydronephrosis. These include:
– Pelvi-ureteric junction obstruction
Figs. 8.4 and 8.5 Clinical photographs showing hydro-
ureters and dysplastic atrophic kidneys secondary to VUR (11 %)
– Vesicoureteral reflux (9 %)
– Mega ureter (4 %)
urethral valve or stricture or neurogenic – Multicystic dysplastic kidney (2 %)
bladder. – Ureterocele (2 %)
• More than 50 % of boys with posterior ure- – Posterior urethral valves (1 %)
thral valves have VUR. This can be unilateral
or bilateral (Figs. 8.6 and 8.7).
• Dysfunctional voiding, with its inherent
increase in intravesical pressure also results • Vesicoureteral reflux (VUR) may be associated
in VUR, even in otherwise healthy with:
children. – Urinary tract infection (UTI)
• The incidence of VUR is much higher in chil- – Hydronephrosis
dren with febrile UTIs (i.e., 30–70 %). – Abnormal kidney development (renal
• The incidence of prenatally diagnosed hydro- dysplasia)
nephrosis caused by VUR ranges from 17 % to – Increased risk for pyelonephritis, hyperten-
37 % in the pediatric population. sion, and progressive renal failure.
• Approximately 20–30 % of children with • VUR with concomitant UTI if not recognized
VUR present with renal lesions (Fig. 8.8). and treated may lead to long-term effects on
• The incidence of VUR in children and young renal function and overall patient health.
adults with end-stage renal failure that • The severity of VUR greatly varies and thus
necessitates dialysis or transplantation is may affect patients differently. Some individu-
about 6 %. als have a genetic predisposition to renal injury.
• VUR is the fifth-most-common cause of end- • Early diagnosis and vigilant monitoring of
stage renal failure in children. VUR are the cornerstones of management.
Figs. 8.6 and 8.7 Micturating cystourethrograms showing posterior urethral valve and VUR. Note the dilated poste-
rior urethra
• The outer longitudinal layer is enveloped by

ureteral adventitia.
• The inner longitudinal layer of smooth muscle
passes through the ureteral hiatus, continues dis-
tally beyond the ureteral orifice into the trigone,
and intertwines with the smooth muscle fibers of
the contralateral ureter, forming the Bell muscle
Fig. 8.8 A clinical intraoperative photograph showing a
duplex system with hydroureter secondary to VUR and
of the trigone and posterior urethra.
dysplastic kidney • The middle circular muscle fibers, outer longi-
tudinal muscle fibers, and periureteral adven-
titia merge with the bladder wall in the upper
8.2 Pathophysiology part of the ureteral hiatus to form the Waldeyer
sheath.
• Anatomically, the ureter enters the urinary blad- • This sheath attaches the extravesical portion
der through a hiatus in the detrusor muscle. of the ureter to the ureteral hiatus.
• The ureter is composed of three muscle layers: • The normal valve mechanism of the uretero-
inner longitudinal, middle circular, and outer vesical junction includes:
longitudinal. – Oblique insertion of the intramural ureter
– Adequate length of the intramural portion one-way valve mechanism becomes incompe-
of the ureter tent, resulting in reflux.
– Strong detrusor support. • It was found that the ratio of tunnel length to
• The distal ureter then passes obliquely ureteral diameter is important in the one-way
through a submucosal tunnel before opening mechanism.
into the bladder lumen via the ureteral • A ratio of at least 5:1 is important to ensure a
orifice. competent one-way valve to prevent reflux.
• This creates a tunnel of about 1–2 cm long • An abnormal short intramural tunnel results in
into the wall of the urinary bladder. a malfunctioning flap-valve mechanism and
• This tunnel is compressed as the bladder fills urine tends to reflux up the ureter and into the
and the intravesical pressure increases pre- collecting system (VUR).
venting backflow of urine from the urinary • It was estimated that refluxing ureters have an
bladder to the upper urinary tract. intramural tunnel length–to–ureteral diameter
• The length of this submucosal tunnel and ratio of 1.4:1.
the muscular coat is important in creating a • When this protective mechanism fails, VUR
one-way valve preventing backflow of occurs.
urine. • VUR will lead to ascending infection and
• If the length of the submucosal tunnel is short pyelonephritis which are the essential causes
or if the muscular backing is inadequate, the of reflux nephropathy.
Vesicoureteral reflux
Urinary tract infection and Pyelonephritis
Renal scarring
Chronic kidney disease
Decreased renal Proteinuria End stage

Hypertension
function renal disease
(ESRD)
• A close correlation was established between the response and a release of oxygen free radicals.
frequency of UTI and severity of reflux nephrop- The release of oxygen free radicals and pro-
athy in patients with vesicoureteral reflux. teolytic enzymes results in fibrosis and scar-
• Renal scarring may result from a single episode of ring of the affected renal parenchyma during
pyelonephritis, especially in very young patients. the healing phase.
• Most renal scarring tends to occur at the renal • This initial scar formation at the infected polar
poles, where the anatomy of the renal papillae region distorts the neighboring papillae and
permits backflow of urine into the collecting converts simple papillae into compound
ducts. papillae.
• This phenomenon is referred to as intrarenal • Compound papillae, in turn, perpetuate fur-
reflux and gives pathogenic bacteria access to ther intrarenal reflux which further increases
the renal tubules. renal scarring.
• The human kidney contains two types of renal • Compound papillae are most commonly found
papillae: at the renal poles, where renal scarring is most
– Simple (convex) papilla commonly observed.
– Compound (concave) papilla • These focal areas of renal scars can be detected
• Compound papillae are commonly seen at the by Renal scan (DMSA).
polar regions of the kidney, whereas simple • Diffuse lesions on renal scan are believed to
papillae are located at nonpolar regions of the be due to renal dysplasia, which results from
kidney. abnormal kidney development.
• Approximately 66 % of human papillae are • It is observed in patients who have higher
simple (convex) and 33 % are compound grades of reflux (IV and V) and who have never
(concave). had any evidence of UTI or pyelonephritis.
• Intrarenal reflux or retrograde movement of • Intrarenal reflux of sterile urine (under normal
urine from the renal pelvis into the renal intrapelvic pressures) has not been shown to
parenchyma is a function of intrarenal papilla. produce clinically significant renal scars.
• Simple papillae possess oblique, slit like, duc- • Treatment with long-term low-dose antibiotic
tal orifices that close upon increased intrarenal prophylaxis to maintain sterile urine appears
pressure and do not allow intrarenal reflux. to inhibit renal scarring in children with
• Compound papillae possess gaping orifices uncomplicated VUR.
that are perpendicular to the papillary surface • Thus, renal scars appear to develop only in the
that remain open upon increased intrarenal presence of intrarenal reflux of infected urine.
pressure allowing free intrarenal reflux. • One exception to this is intrarenal reflux of
• Renal scars are often present at initial diagno- sterile urine in the presence of abnormally
sis of VUR and usually develop during the high intravesical pressures.
first years of life. • Abnormally high intravesical pressure is seen
• Persistent intrarenal reflux causes renal scar- in:
ring and eventual reflux nephropathy. – Bladder outlet obstruction (functional or
• Reflux nephropathy leads to: anatomical)
– Impaired renal function – Nonneurogenic neurogenic bladder, or
– Hypertension Hinman syndrome
– Proteinuria – Gastrointestinal dysfunction including
– End stage renal disease chronic constipation
• These effects depend on the type of urine. – Children with overactive bladder (e.g.
• Two types of urine may reflux and enter the detrusor hyperreflexia, detrusor instability)
renal papillae: infected urine or sterile urine. • Renal lesions are associated with higher
• Intrarenal reflux of infected urine is primarily grades of reflux.
responsible for the renal damage. • Renal units with low-grade reflux may grow
• The presence of bacterial endotoxins (lipo- normally, but high grades of reflux are associ-
polysaccharides) activates the host’s immune ated with renal growth retardation.
8.3 Classification of VUR 243
• Pyelonephritic scarring may, over time, cause • This defect causes inadequacy of the
serious hypertension due to activation of the valvular mechanism and failure of
renin-angiotensin system. its function as a one-way valve lead-
• Scarring related to VUR is one of the most ing to backflow of urine from the
common causes of childhood hypertension. urinary bladder to the ureters and
• It was estimated that hypertension develops in kidneys.
10 % of children with unilateral scars and in • This defect can be unilateral or bilateral
18.5 % with bilateral scars. (Fig. 8.11)
• Approximately 4 % of children with VUR
progress to end-stage renal failure.
8.3 Classification of VUR
• VUR is classified into two types:

– Primary VUR:
• This is the most common type of VUR
(Figs. 8.9 and 8.10).
• It is caused by a defect in the development of
the valve-like effect at the uretrovesical
junction with insufficient submucosal ureteric
length relative to its diameter.
• This type is usually detected antenataly
or shortly after birth.
• Primary reflux is vesicoureteral reflux in
an otherwise normally functioning
lower urinary tract.
• This is precipitated by a congenital defect.
• Lack of longitudinal muscle of the intra-
Fig. 8.11 A micturating cystourethrogram showing bilat-
vesical ureter result in anomaly of the eral VUR
ureterovesicular junction (UVJ).
Figs. 8.9 and 8.10 Micturating cystourethrogram showing severe VUR. Note the dilated tortous ureters
Figs. 8.12 and 8.13 Micturating cystourethrograms showing posterior urethral valve and associated secondary
VUR. Note the dilated posterior urethra and the diverticulae from the urinary bladder
– Secondary VUR: • This is seen in those with posterior ure-

• Secondary reflux is vesicoureteral reflux thral valves (anatomical) or a neuro-
that is associated with or caused by an genic bladder (functional).
obstructed or poorly functioning lower • The main causes of secondary VUR are:
urinary tract. – Posterior urethral valves (Figs. 8.12,
• In this category the valvular mechanism 8.13, 8.14, and 8.15)
is intact and healthy to start with but – Neurogenic bladder
becomes overwhelmed by raised – Urethral stricture (Figs. 8.16 and
intravesicular pressures associated with 8.17)
obstruction. – Meatal stenosis
• This leads to distortion of the uretero- • VUR is also classified into five grades:
vesical junction and failure of its func- – Voiding cystourethrography (VCUG) is the
tion as a one-way valve. criterion standard in diagnosis of VUR,
• Secondary VUR can be further divided providing precise anatomic detail and
into anatomical and functional groups. allows grading of the reflux.
8.3 Classification of VUR 245
Figs. 8.14 and 8.15 Micturating cystourethrograms showing posterior urethral valve without VUR
Figs. 8.16 and

8.17 Micturating
cystourethrogram
showing urethral
stricture secondary to
hypospadias repair and
secondary mild VUR
Figs. 8.18 and 8.19 Diagrammatic representation of grade I VUR. The blue color represents urine in the ureter
– The International Classification System for

VUR is based on the radiographic
appearance of the ureter, renal pelvis and
calyces on a voiding cystogram.
– It is important to note that the presence of a
severe reflux on one side may hide a milder
degree of reflux on the other side in those
with bilateral reflux.
– In these cases reflux on the milder side may
appear postoperatively following treatment
of the more severely affected side.
– This is one of the causes of appearance of
reflux on the contralateral side following
successful treatment of the severely Fig. 8.20 A micturating cystourethrogram showing
affected side. grade I VUR
– The International Classification System for
VUR is as follows: • Grade III – Reflux with mild to moder-
• Grade I – Reflux into nondilated ureter ate dilation and minimal blunting of for-
(Figs. 8.18, 8.19, and 8.20) nices (Figs. 8.23, 8.24, and 8.25)
• Grade II – Reflux into renal pelvis and • Grade IV – Reflux with moderate ure-
calyces without dilation (Figs. 8.21 teral tortuosity and dilation of pelvis
and 8.22) and calyces (Figs. 8.26, 8.27, and 8.28)
8.4 Etiology of VUR 247
Figs. 8.21 and 8.22 Diagrammatic representation of grade II VUR and a micturating cystourethrogram showing grade
II VUR
8.4 Etiology of VUR
• VUR is prevented by a one way valve like

effect at the uretero-vesical junction.
• This is attributed to several factors
including:
– The oblique entrance of the ureter into the
urinary bladder
– The submucosal tunnel through which the
ureter enter into the urinary bladder
– The ureter’s muscular attachments
• Failure of this mechanism will result in retro-
grade flow of urine.
• VUR is divided into two types based on
etiology:
Fig. 8.23 A micturating cystourethrogram showing – Primary VUR
grade III VUR – Secondary VUR
• Primary VUR:
• Grade V – Reflux with gross dilation of – Primary VUR is the most common form of
ureter, pelvis, and calyces, loss of papil- reflux
lary impressions, and ureteral tortuosity – It is due to incompetent or inadequate
(Figs. 8.29, 8.30, and 8.31) ureterovesical junction (UVJ)
Figs. 8.24 and 8.25 Diagrammatic representation of grade III VUR and a micturating cystourethrogram showing
grade III VUR. Note the hydronephrotic pelvic right kidney
– The exact cause of the defect in primary – This is seen in children with congenital
VUR is unknown bladder outlet obstruction and neurogenic
– This may be secondary to an abnormally bladder (Figs. 8.32 and 8.33).
short intravesical ureteric segment or – More than 50 % of boys with posterior ure-
abnormal surrounding muscles. thral valves have vesicoureteral reflux
– Other factors that contribute to the etiology (Figs. 8.34 and 8.35).
of primary VUR include: – In these patients, VUR can be unilateral or
• The existence of a strong genetic compo- bilateral
nent is supported by the high rate of reflux – Other causes include urethral or meatal
in relatives of patients with reflux, but the stenosis
mechanism of transmission is not clear. – Bladder instability, neurogenic bladder and
• The possibility of urinary tract infection non-neurogenic bladder
as a cause of VUR is not clear and many – Dysfunctional voiding, with its inherent
think that UTI and VUR are indepen- increase in intravesical pressure, is a cause
dent variables. Urinary tract infections reflux, even in otherwise healthy children.
may cause reflux due to the elevated – The combination of high-pressure voiding
pressures associated with inflammation. and vesicoureteral reflux increases the risk
• Secondary VUR: of pyelonephritis beyond that of the child
– Secondary VUR is reflux that is associated with low-pressure reflux.
with or caused by an obstructed or poorly – A unique group of children presents with
functioning lower urinary tract. dysfunctional elimination, which consists
8.4 Etiology of VUR 249
Figs. 8.26, 8.27, and 8.28 Diagrammatic representation of grade IV VUR and Micturating cystourethrograms show-
ing grade IV VUR
of a symptom complex heralded by – Hardikar syndrome: This include:

infection, severe constipation, and daytime • Vesicoureteral reflux
wetting (Figs. 8.36, 8.37, and 8.38). • Hydronephrosis
– Some of these children have infrequent void- • Cleft lip and palate
ing and incomplete bladder emptying, which • Intestinal obstruction and other
further increases the likelihood of UTI. symptoms
8.5 Clinical Features
• VUR cannot be diagnosed prenatally.

• VUR however may be suspected in the prena-
tal period, when transient dilatation of the
upper urinary tract is noted in conjunction
with bladder emptying.
• Approximately 10 % of neonates diagnosed
prenatally with dilatation of the upper uri-
nary tract will be found to have VUR
postnatally.
• In general, VUR is almost always
asymptomatic.
• VUR does not cause any specific signs or
symptoms unless complicated by UTI (febrile
UTI).
• Most infants and children with vesicoureteral
reflux (VUR) present in one of two distinct
groups:
– The first group presents with hydronephro-
sis, often prenatally identified using
ultrasonography.
– The second group presents with urinary
Fig. 8.29 Diagrammatic representation of grade V VUR tract infection (UTI).
Figs. 8.30 and 8.31 A micturating cystourethrogram showing grade V VUR. Note the dilated tortuous ureters
• Clinical signs and symptoms associated

Etiology of VUR with a febrile UTI in a neonate may
• Primary causes of VUR: include:
– Short or absent intravesical ureter – Irritability
– Absence of adequate detrusor – Persistent high fever
backing – Listlessness
– Lateral displacement of the ureteral – Infection in infants can manifest as failure
orifice to thrive, with or without fever.
– Paraureteral (Hutch) diverticulum – Other features include vomiting, diarrhea,
• Secondary causes of VUR: anorexia, and lethargy
– Cystitis or UTI • In cases of VUR and febrile UTI associated
– Bladder outlet obstruction (Posterior with a serious underlying urinary tract
urethral valve, urethral stricture, abnormality, the neonate could present
meatal stenosis) with respiratory distress, failure to thrive,
– Neurogenic bladder renal failure, flank masses, and urinary
– Detrusor instability ascites.
Figs. 8.32 and 8.33 Micturating cystourethrograms showing neurogenic bladder with VUR
Figs. 8.34 and 8.35 Micturating cystourethrograms showing posterior urethral valve and severe right vesicoureteral
reflux. Note the dilated posterior urethra
• Older children with VUR and UTI may pres- and small in size as measured by
ent with: ultrasound.
– Nonspecific signs and symptoms – Children occasionally present with
– Urgency advanced reflux nephropathy, manifesting
– Frequency as headaches or congestive heart failure
– Dysuria from untreated hypertension, or with ure-
– Abdominal pain mic symptoms from renal failure.
– Incontinence – A small group of children without evi-
– Unless the UTI is associated with a fever, dence of UTI present with symptoms of
there is little reason to suspect VUR. sterile reflux, which can include flank
– Sometimes an enlarged urinary bladder or abdominal pain before or during
may be palpable (Fig. 8.39). voiding, as well as double voiding or
– A palpable kidney is sometimes seen in incomplete emptying resulting from
those with associated hydronephrosis. delayed drainage of urine out of the
Usually the affected kidney is not palpable upper tracts.
Figs. 8.36, 8.37, and 8.38 Plain abdominal radiograph and micturating cystourethrogram showing bowel dysfunction
with chronic constipation and VUR
– Growth of more than 100,000 CFU/mL is a

significant finding on a midstream-voided
specimen.
– Suprapubic urine aspiration is used in
infants and children.
– Any growth in suprapubic urine sample
should be considered significant.
– Urethral catheterization is an alternative
way to obtain a clean urine sample but it is
more invasive.
– Growth of more than 1,000 colony-form-
ing units (CFU)/mL is considered signifi-
cant in a urine sample obtained by urethral
catheterization.
– The least reliable method is the most com-
mon method of obtaining a urine specimen
in babies. A urine sample is obtained from
a urine collection bag. This method is not
reliable and should be discouraged.
Fig. 8.39 A micturating cystourethrogram showing grade
– This method is more useful if there is no
V VUR. Note also the enlarged urinary bladder
growth in the urine sample as false-negative
results are unlikely.
– As many as 10 % of urine specimens
8.6 Investigations obtained by this method grow more than
50,000 CFU/mL with no correlation to
• VUR not only increases the frequency of actual presence of infection.
UTI’s, but also the risk of damage to upper • Imaging studies are the basis of diagnosis and
urinary structures. management of VUR.
• Vesicoureteral reflux can result in substantial • The standard imaging tests include renal and
morbidity, both from acute infection and from bladder ultrasonography and voiding cysto-
the sequelae of reflux nephropathy. urethrography (VCUG) (Figs. 8.40 and 8.41).
• Early diagnosis and treatment of VUR is cru- • Indications for imaging studies are as
cial to avoid permanent renal cortical scarring follows:
and subsequent renal insufficiency. – After the first UTI in all children younger
• CBC than 5 years
• ESR and C-reactive protein – Children of any age with febrile UTI
• BUN, serum electrolytes and creatinine – Boys of any age with UTI
• The diagnosis of UTI depends on urine analy- – Children with prenatally diagnosed hydro-
sis and urine culture. nephrosis should be evaluated postnatally.
• The 2011 American Academy of Pediatrics – Ultrasonography should be performed after
(AAP) guidelines specify that both a urinaly- the first 3 days of life.
sis showing pyuria and a culture growing – Ultrasonography performed during the first
more than 50,000 CFU/mL should be the basis 3 days of life may have a high rate of false-
for a diagnosis of UTI. negative results because of relative dehy-
• To diagnose UTI, it is important to obtain a dration during the neonatal period.
non-contaminated urine specimen. • The following radiological investigations can
– A clean-catch midstream urine specimen is be performed to evaluate for VUR:
the most acceptable method especially in • Ultrasonography
children who are toilet trained. • VCUG or radionuclide cystography (RNC)
8.6 Investigations 255
Figs. 8.40 and 8.41 Micturating cystourethrograms showing severe VUR
• Some advocate that children with a history of – Ultrasonography is not useful to diagnose
febrile UTI undergo a dimercaptosuccinic or rule out VUR.
acid (DMSA) renal scan, to assess for evi- – A normal ultrasonography does not exclude
dence of kidney involvement, kidney scarring, vesicoureteral reflux.
or both; if DMSA scan findings are positive, – Ultrasonography is useful to detect upper
VCUG is recommended. urinary tract obstruction, to detect dilated
• Others advocate performing RNC as the ini- ureters and renal scarring.
tial screening test in girls and then to perform – All children with a history of febrile UTI
standard VCUG when VUR is observed. should undergo kidney and bladder
• Other clinicians use VCUG for the initial ultrasonography.
diagnosis and use RNC for follow-up – Abdominal ultrasound is usually normal in
studies. those with low to moderate VUR.
• The 2011 American Academy of Pediatrics – An abdominal ultrasound might suggest
(AAP) guidelines for management of UTI in chil- the presence of VUR if ureteral dilatation is
dren aged 2–24 months recommend that VCUG present.
not be performed after an initial febrile UTI. • Voiding cystourethrography (VCUG):
• Abdominal ultrasound: – This is the method of choice for diagnosing
– The 2011 AAP guidelines recommend that and grading VUR.
ultrasonography alone should be the initial – VCUG provides precise anatomic detail
screening test for children after UTI. and allows grading of the reflux.
– The Society for Pediatric Urology contin- – The International Classification System for
ues to recommend that both ultrasonogra- VUR is as follows:
phy and cystography be performed. • Grade I: Reflux into nondilated ureter
• Grade II: Reflux into renal pelvis and • Dimercaptosuccinic acid (DMSA) renal scan:
calyces without dilation – Although the traditional approach in chil-
• Grade III: Reflux with mild to moderate dren with UTI has been evaluation for vesi-
dilation and minimal blunting of fornices coureteral reflux with VCUG or
• Grade IV: Reflux with moderate ureteral radionuclide cystography (RNC), some
tortuosity and dilation of pelvis and authorities are now advocating a “top-
calyces down” approach for children with UTI.
• Grade V: Reflux with gross dilation of – In this approach, a child with a history of
ureter, pelvis, and calyces, loss of papil- febrile UTI undergoes a dimercaptosuc-
lary impressions, and ureteral tortuosity cinic acid (DMSA) renal scan to assess for
– VCUG should not be performed in the evidence of kidney involvement, kidney
presence of UTI and should be delayed till scarring, or both.
the child has fully recovered from the – Negative DMSA scan findings suggest
UTI. This should be confirmed with a fresh that clinically significant vesicoureteral
urine analysis and culture. reflux is unlikely, obviating the need for
– Performance of VCUG during an episode VCUG.
of acute cystitis can result in overestima- – However, if DMSA scan findings are posi-
tion of the grade of reflux because of paral- tive, VCUG is recommended.
ysis and laxity of the ureteral musculature – Reflux grade was significantly associated
by bacterial endotoxin. Conversely, some with the prevalence of renal scarring.
children demonstrate reflux only during an – VCUG is recommended after the first acute
episode of cystitis. episode of infection is confirmed using
– VCUG outlines the urethra in males with dimercapto-succinic acid scintigraphy.
posterior urethral valves. – Areas of acute inflammation or scarring do
– VCUG provides information in both boys not take up the radiopharmaceutical and
and girls about bladder capacity and emp- are revealed as cold spots on imaging.
tying and may reveal signs of outlet – DMSA is used to identify and monitor pro-
obstruction, such as bladder trabeculae or gression of renal scarring.
diverticula. – Patients who are medically treated and
– Standard VCUG is recommended as the develop new or progressive scarring are
initial study in boys. often considered candidates for surgical
• Radionuclide cystography: correction of vesicoureteral reflux.
– This is performed by instillation of – DMSA can also be used as a diagnostic
technetium-99m pertechnetate into the blad- tool during suspected episodes of acute
der and observation with a gamma camera. pyelonephritis but this role is not well
– This is a highly sensitive test to diagnose defined.
VUR. • Urodynamic studies (Cystometrography):
– The disadvantage of this investigation is – These reveal functional abnormalities of
the poor anatomical detail and failure to the lower urinary tract.
precisely classify the degree of VUR. – These studies are however difficult to per-
– Grade I reflux is poorly detected by this form in infants and small children.
study, because the distal ureters are com- – Urodynamic studies are important in
monly obscured by the bladder patients with secondary VUR, such as
– Grading of VUR by nuclear cystography is patients with spina bifida, detrusor instabil-
limited to mild, moderate, and severe ity or boys whose VCUG is suggestive of
grades. residual posterior urethral valves.
– Many clinicians use VCUG for the initial – Antireflux surgery is much less successful
diagnosis and use RNC for follow-up in patients with secondary reflux, and
studies. because of this it is important to identifying
8.7 Management 257
Figs. 8.42 and 8.43 Abdominal CT-scan showing sever hydronephrosis secondary to VUR
such patients before proceeding with oper- – The presence or absence of urinary tract
ative correction of VUR. infections and the frequency of urinary
– The cystometrography gives useful infor- tract infections.
mation about: – The presence of renal scarring
• Bladder capacity and leak point • The aims of treatment are:
• Pressures at various stages of filling – To prevent episodes of acute
• The presence and frequency of uninhib- pyelonephritis
ited (involuntary) bladder contractions – To prevent scarring of the kidney associ-
and compliance. ated with VUR (reflux nephropathy), which
• Abdominal and pelvic CT-scan and MRU increases the risk of hypertension and renal
(Figs. 8.42, 8.43, 8.44, 8.45, 8.46, and 8.47): failure
– These are useful in delineating: • Although medical conservative treatment of
• The anatomy and cause as well as the VUR is well established, controversy
degree of ureteric dilatation continues regarding the timing, surgical tech-
• Hydronephrosis nique, and benefits.
• Renal parenchymal thickness • Three approaches are used to treat children
with vesicoureteral reflux (VUR):
– Surveillance (observation)
8.7 Management – Medical treatment
– Surgical treatment
• VUR is known to be associated with morbid- • The first goal of treatment is to prevent or
ity and sometimes mortality. minimize urinary tract infection.
• The management of VUR depends on several • Medical management is recommended in chil-
factors including: dren with Grade I-III VUR as most cases will
– The grade of VUR resolve spontaneously.
– The compliance of patients with medica- • This is primarily done by prophylactic
tions and follow-up antibiotics
Figs. 8.44 and 8.45 Abdominal CT-scan showing sever hydronephrosis secondary to VUR. Note the dilated ureters
and urinary bladder. Note the associated duplex kidneys
Figs. 8.46 and 8.47 Abdominal CT-scan showing severely dilated ureters secondary to VUR. Note the dilated ureters
and urinary bladder
8.7 Management 259
• An important aspect of conservative manage- absence of renal scarring at diagnosis, and

ment is bowel and bladder management. the age at diagnosis.
• Children who hold their bladder or who are – For children without renal scarring at diag-
constipated have a greater number of infec- nosis, recommendations are as follows:
tions than children who void on a regular • Diagnosis made in infancy:
schedule. – All patients diagnosed at infancy
• Failure of medical treatment to prevent recur- (i.e. <1 year) with grades I–V reflux
rent urinary tract infections, or if the kidneys should be treated initially with con-
show progressive renal scarring are indica- tinuous prophylactic antibiotics.
tions for surgical interventions. • Diagnosis made in children aged
• A trial of medical treatment is indicated in 1–5 years:
patients with Grade IV VUR especially – When unilateral and/or bilateral
younger patients or those with unilateral VUR. grades I–IV reflux or unilateral
• Patients with Grade V VUR are treated surgi- grades III–V reflux are diagnosed in
cally except infants who are treated medically children aged 1–5 years, they should
before surgery is indicated. be treated initially with continuous
prophylactic antibiotics.
• Diagnosis made in children aged
8.7.1 Medical Treatment of VUR 6–10 years:
– Children diagnosed at age 6–10 years
• This is based on the fact that low-grade VUR with unilateral and/or bilateral
resolve spontaneously and sterile reflux does grades I–II reflux and unilateral
not damage the kidney. grades III–IV reflux should be
• Medical treatment with prophylactic antibiot- treated initially with continuous
ics remains the mainstay of initial manage- antibiotic prophylaxis.
ment of vesicoureteral reflux. – However, some experts advocate
• Because vesicoureteral reflux spontaneously withholding treatment in patients
resolves in most children, medical manage- with grade I or II VUR, as most of
ment allows this natural history to take its these patients are at low risk for UTIs
course while providing some measure of pro- and pyelonephritis provided they
tection against recurrent UTI and renal have no voiding dysfunction or
injury. constipation.
• The International Reflux Study has found – For children with renal scarring at diagno-
that children can be managed nonsurgically sis, recommendations are as follows:
with little risk of new or increased renal scar- • Diagnosis made in infancy:
ring, provided they are maintained infection – Infants (i.e. <1 year) with grades I–V
free. reflux should be treated initially with
• The chance of spontaneous resolution of continuous antibiotic prophylaxis.
reflux is high in children younger than 5 years • Diagnosis made in children aged
with grades I-III reflux and in children younger 1–5 years:
than 1 year (especially boys). – Antibiotic prophylaxis is the pre-
• Even higher grades of reflux (grades IV–V) ferred option for preschool-aged
may resolve spontaneously as long as the children (i.e., 1–5 years) with renal
child remains infection free. scarring at diagnosis, unilateral and/
• Antibiotic prophylaxis: or bilateral grades I–II reflux, unilat-
– The recommendations for antibiotic pro- eral grades III–IV reflux, and bilat-
phylaxis vary according to the presence or eral grades III–IV reflux.
• Diagnosis made in children aged – Regular follow-up and compliance with

6–10 years: prophylactic antibiotics are important to
– In children diagnosed at age avoid the complications of VUR.
6–10 years with renal scarring and – Once follow-up imaging demonstrates res-
unilateral and/or bilateral grades I–II olution of vesicoureteral reflux, antibiotics
reflux or unilateral grades III–IV are discontinued.
reflux, antibiotic therapy is the pre- – Incomplete bladder emptying and consti-
ferred treatment option. pation are important etiological factors.
• The initial treatment of the child with a UTI – The importance of aggressive bladder and
involves: bowel management for dysfunctional elim-
– Supportive care ination cannot be overemphasized.
– Prompt administration of appropriate – These patients benefit from bladder train-
antibiotics ing and sometimes the use of anticholiner-
– Timely institution of antibiotic therapy has gic medications.
been shown to be critical in preventing scar – Constipation should be avoided and chil-
formation in kidneys with pyelonephritis. dren with primary bowel elimination prob-
A high index of suspicion for UTI in chil- lem should be treated with enemas, dietary
dren is important. changes, and stool bulking agents.
• Since a substantial number of children experi- • In 2014, the results of the Randomized
ence spontaneous resolution of VUR, medical Intervention for children with Vesicoureteral
treatment spares this group the morbidity of Reflux (RIVUR) study showed that antibiotic
surgery while protecting the kidneys from fur- prophylaxis with trimethoprim-sulfame-
ther damage. thoxazole was associated with a decrease of
• Prophylaxis should be started once a child has approximately 50 % in the incidence of recur-
completed treatment of the initial UTI and rent UTI among children with VUR, in com-
continues at least until imaging reveals vesi- parison with placebo.
coureteral reflux. • Children on medical management of vesico-
– If no vesicoureteral is seen, prophylaxis is ureteral reflux are regularly seen on an outpa-
discontinued. tient basis.
– If vesicoureteral reflux is present, prophy- • Routine evaluation includes:
lactic antibiotics are continued until: – Urinalysis and urine culture
• Vesicoureteral reflux resolves – Appropriate imaging, and blood pressure
• Vesicoureteral reflux is surgically measurement.
corrected – Parents can be taught how to perform uri-
• The child grows old enough that prophy- nalysis at home and report positive home
laxis is deemed no longer necessary. urinalysis.
• Virtually all children with a new diagnosis of – Parents should be aware of UTI and seek
grade I–IV reflux, and some with grade V, are medical care.
given a trial of medical treatment. • Spontaneous resolution rates decrease as
• This consists of: patient age increases and with higher grades
– Antibiotics given at one fourth of the thera- of reflux.
peutic dosage • Surgical intervention is recommended for
– Regular follow-up care and imaging. children with reflux that has persisted for
– Regular follow-up consists of renal ultra- more than 3 years with no improvement in
sonography and VCUG or nuclear cystog- the grade of reflux if it is grade II or
raphy every 12–18 months. greater.
8.7 Management 261
8.7.2 Antibiotics Used Prophylaxis for pediatric UTIs

for Prophylaxis Drug Dosage
TMP-SMX 2 mg/kg/dose once daily or
• Conservative, nonsurgical management is 5 mg/kg/dose twice per week
appropriate for mild-to-moderate VUR Nitrofurantoin 1–2 mg/kg/dose once daily
(grades I–IV) in the absence of breakthrough Ampicillin 20 mg/kg/dose once daily
infections or anatomic abnormalities. Amoxicillin 10 mg/kg/dose once daily
• Antibacterial prophylaxis decreases the inci- Cephalexin 10 mg/kg/dose once daily
dence of pyelonephritis and subsequent renal
scarring with its long term effects for low-to-
moderate grades of VUR.
• Long-term antibiotic prophylaxis however, 8.7.3 Anticholinergics
was not shown to be beneficial in those with
repeated urinary tract infections. • One of the secondary causes of VUR is detru-
• In fact, in these patients prophylactic antibiot- sor over activity.
ics will lead to increased risk of bacterial • These patients may benefit from
resistance to commonly used antibiotics. anticholinergics
• Trimethoprim-sulfamethoxazole (Bactrim, • These are bladder relaxant medications that
Bactrim DS, Septra, Septra DS) is an control detrusor over activity.
effective antibiotic used to treat uncompli- • Oxybutynin (Ditropan):
cated UTIs and prevent recurrent infec- – It inhibits action of acetylcholine on
tions. It is commonly used as an antibiotic smooth muscle and has direct antispasmodic
prophylaxis. effect on smooth muscles, which in turn
• In children, it is given orally as a single dose cause bladder capacity to increase and
of 2 mg/kg/day for long term prophylaxis. uninhibited contractions to decrease.
• In children <3 months, amoxicillin is – Oxybutynin is given orally to children in a
preferred. dose of 1–5 mg bid/tid.
• Amoxicillin (Amoxil, Biomox, Trimox) is an • Tolterodine tartrate (Detrol, Detrol LA):
effective antibiotic for treatment of uncompli- – It is a competitive muscarinic receptor
cated or recurrent cystitis and also may be antagonist for overactive bladder.
used as a long-term prophylaxis to prevent – It has selectivity for urinary bladder over
recurrent cystitis. salivary glands.
• In children, amoxicillin is given orally as a – It exhibits a high specificity for muscarinic
single dose of 10 mg/kg/day for long term receptors and has minimal activity or affin-
prophylaxis. ity for other neurotransmitter receptors and
• Nitrofurantoin (Furadantin, Macrobid, other potential targets, such as calcium
Macrodantin) is an antibiotic used specifically channels.
for uncomplicated lower UTIs. – In adults, the dose of Detrol is 1–2 mg PO
• It is given for children >3 months for long bid.
term prophylaxis. • Other important measures to control dysfunc-
• In children >3 months, Nitrofurantoin is given tional elimination:
orally as a single dose of 1–2 mg/kg/day. – It is important to ensure that the child emp-
• Double-suppressive regimens of TMP-SMX ties his/her bladder completely at regular
every morning and nitrofurantoin every eve- intervals (every 3 h)
ning may be effective when single-agent pro- – Adequate oral hydration
phylaxis fails. – Treatment and prevention of constipation
• In children with dysfunctional voiding due to – A desire to terminate antibiotic prophy-

Hinman syndrome, it is important to ensure: laxis (either by the physician or the patient/
– Timed voiding with or without parents)
biofeedback – Medical noncompliance
– A regular bowel regimen
– Intermittent catheterization
8.8.2 Indications for Surgical
Interventions Based on Age
8.7.4 Surveillance at Diagnosis and the Presence
or Absence of Renal Lesions
• In general, low-grade reflux (grades I–II) have
high rates of spontaneous resolution, usually Children without renal lesions at diagnosis:
more than 80 %.
• High-grade reflux, especially grade V, is much • In patients diagnosed with VUR in infancy
less likely to resolve. (<1 year):
• Surveillance is infrequently used among those – Surgical repair may be recommended in
with high-grade VUR. patients with persistent unilateral grades
• Surveillance is still frequently used among IV–V reflux or bilateral grades III–V reflux
older children with VUR, especially boys who after a period of antibiotic therapy should
have never had a UTI. the parents prefer definitive therapy over
• Children with low-grade VUR, especially watchful management plus antibiotic
those who have never had UTI, are sometimes prophylaxis.
followed on surveillance without antibiotic • In children diagnosed at age 1–5 years:
prophylaxis. – Continuous antibiotic prophylaxis is the
preferred option as an initial therapy for
those with unilateral grade IV reflux; how-
8.8 Surgical Therapy of VUR ever, surgical repair is a reasonable alterna-
tive for grades IV and V reflux.
8.8.1 Indications for Surgical – In patients with bilateral grade IV and V
Interventions reflux, surgical repair is recommended.
– Surgery is recommended for children with
• Absolute indications for surgical interventions persistent grades III–V reflux who have not
include: remained infection-free with antibiotic
– Breakthrough pyelonephritis therapy.
– Progressive renal scarring in patients – Endoscopic treatment may be recom-
receiving antibiotic prophylaxis mended in children with grade III–IV who
– An associated ureterovesical junction have not shown any improvement in the
abnormality reflux grade, who do not wish to receive
• Relative indications for surgical interventions further antibiotics, or who have had UTI.
of VUR include: • In children diagnosed at age 6–10 years:
– Grades IV and V VUR – In patients with bilateral grades III–IV
– Persistent VUR despite medical prophy- reflux, surgical repair is the preferred
laxis (beyond 3 years) option, although continuous antibiotic
– Breakthrough UTIs in patient who are therapy is a reasonable alternative.
receiving antibiotic prophylaxis – Patients with grade V reflux should undergo
– Lack of renal growth surgical repair.
– Multiple drug allergies that preclude the – In patients with persistent grades I–II reflux
use of prophylaxis after a period of antibiotic prophylaxis,
8.8 Surgical Therapy of VUR 263
consensus is lacking regarding the role of – Consensus is lacking regarding the role
continued antibiotics versus surgery. of continued antibiotics versus surgery
– Surgery is an option for persistent reflux in for patients with persistent grades I–II
children with grades III–IV reflux in whom reflux after a period of antibiotic
initial antibiotic therapy has failed; either prophylaxis.
an open surgical or an endoscopic approach – Girls with persistent unilateral and/or bilat-
may be used. eral grades III–IV reflux and boys with per-
sistent bilateral grades III–IV reflux should
Children with renal lesions at diagnosis: undergo surgical repair, either open or
endoscopic.
• In patients diagnosed with VUR in infancy – Surgery is also an option for boys with per-
(<1 year): sistent unilateral grades III–IV reflux.
– In children with grade V reflux and scar- – For patients with persistent grade V reflux
ring, continuous antibiotic prophylaxis is who have not undergone surgery as initial
the preferred option as an initial treatment; treatment, surgical repair is recommended.
primary surgical repair is a reasonable • In children diagnosed at age 6–10 years:
alternative. – Patients diagnosed with bilateral grades
– If the kidney is noted to have poor function III–IV reflux or grade V reflux can undergo
(<15 % on DMSA scan) consider removing surgical repair as initial treatment.
the kidney and the ureter down to the – Consensus is lacking regarding the role of
bladder. continued antibiotics versus surgery for
– Consensus is lacking regarding the role of patients with persistent grades I–II reflux
continued antibiotics versus surgery in after a period of prophylaxis.
patients with persistent grades I–II reflux – Patients with persistent unilateral grades
after a period of antibiotic prophylaxis. III–IV reflux who have not undergone sur-
These patients may be candidates for endo- gery as initial treatment should be offered
scopic treatment. either open surgical repair or endoscopic
– In boys with persistent unilateral grades treatment.
III–IV reflux, surgical repair is the pre- • Surgical therapy options for VUR include:
ferred option. – Open surgical procedures
– Boys with persistent bilateral grades III–IV • Leadbetter-Politano procedure
reflux, girls with persistent unilateral and/ • Cohen procedure
or bilateral grades III–IV reflux, and any – Endoscopic injection (STING/HIT
children with persistent grade V reflux procedures)
should undergo surgical repair, with an – Laparoscopic repair
option for endoscopic treatment in grades – Robotic assisted repair
II–IV.
• In children diagnosed at age 1–5 years:
– In children with bilateral grades III–IV 8.8.3 Endoscopic Injection
reflux and renal lesions, antibiotic therapy
is the preferred option; however, surgical • The most dramatic change in the treatment of
repair is a reasonable alternative. vesicoureteral reflux over the past decade has
– Patients with unilateral and/or bilateral been the rapid growth in the use of endoscopic
grade V disease and scarring should treatment.
undergo surgical repair as initial treatment • Endoscopic treatment of VUR was popular-
or nephroureterectomy if the kidney has ized by Puri and O’Donnell in 1980s.
been shown to have little or no function on • Currently, it is the surgical treatment of choice
DMSA scan. for children with VUR.
• The principle of the procedure is to inject, because VUR is known to spontaneously

under cystoscopic guidance, a biocompatible resolve in most children, and even those with
bulking agent underneath the intravesical por- persistent VUR may not have a clinical indi-
tion of the ureter in a submucosal location. cation for antireflux surgery.
• Add to this, the fact that the true long-term
success rates for endoscopic treatment are still
Indications for Surgical Treatment of VUR to be determined.
• Breakthrough febrile UTIs despite ade- • Endoscopic injection involves applying a gel
quate antibiotic prophylaxis around the ureteral opening to create a valve
• Severe reflux (grade V or bilateral like function which stop urine from flowing
grade IV) that is unlikely to spontane- back up the ureter.
ously resolve, especially if renal scar- • Some authors emphasize the importance of
ring is present creating a large mound or “volcanic” appear-
• Mild or moderate reflux in females that ance of the bulking agent under the orifice,
persists as the patient approaches puberty, compressing the orifice into a slit.
despite several years of observation
• Poor compliance with medications or
surveillance programs
Advantages of Endoscopic Treatment of
• Poor renal growth or function or appear-
VUR
ance of new scars
• It is performed on an outpatient basis
• A short surgical time
• Low surgical morbidity
• The bulking agent elevates the ureteral orifice
• Comparable success rates
and distal ureter in such a way that the lumen
• Preservation of the option for subse-
is narrowed, preventing regurgitation of urine
quent open surgical repair
up the ureter but still allowing its antegrade
• It can be repeated
flow.
• The procedure became popular and has sev-
eral advantages:
– It is performed with general anesthesia on • Other authors have described an intramural
an outpatient basis injection, in which the distal ureter is dis-
– A short surgical time tended with a jet of saline from the cysto-
– Low surgical morbidity scope, allowing the injection needle to be
– Comparable success rates advanced into the submucosa of the intramu-
– Preservation of the option for subsequent ral ureter at 6 o’clock.
open surgical repair • The gel consists of two types of sugar-based
– It can be repeated molecules called dextranomer and hyaluronic
– It can be used to treat different grades of acid.
VUR and some authors are using this tech- • Trade names for this combination include
nique to treat even grade IV and V VUR. Deflux and Zuidex.
• Some clinicians and because of these advan- • Both are biocompatible, which means that
tages are now advocating endoscopic treat- they do not cause significant reactions within
ment as initial management for newly the body.
diagnosed vesicoureteral reflux. • The procedure of endoscopic treatment of
• They argue that immediate antireflux surgery VUR:
obviates the need for long-term antibiotics – The procedure is performed under general
and repeated imaging studies. anesthesia and complete aseptic technique.
• This however, inevitably results in the over- – The patient is placed in the lithotomy
treatment of a large number of children position.
– Cystourethroscopy is performed and the • Concerns over particle migration, carcinogen-

bladder and ureteral orifices are inspected. esis, and technical handling problems have
– An injection needle is then introduced limited their use.
advanced, bevel up to the ureteral • Children who undergo endoscopic antireflux
orifice. surgery need continued follow-up.
– The orifice is kept open by hydrodistending – They require post procedure imaging,
it with irrigation fluid. including voiding cystourethrography
– The needle is then advanced into the (VCUG) at 3–4 months postsurgery.
ureter. – Patients should be maintained on antibiotic
– A submucosal puncture is made and the prophylaxis until resolution of vesicoure-
bulking material is slowly injected. teral reflux is confirmed.
– As it spreads in the submucosal space, the • It is important to note that as many as 25 % of
material elevates the intravesical ureter, children whose VUR was cured on the initial
and the orifice acquires an inverted smile post endoscopic injection VCUG (3–4 months)
appearance. subsequently had recurrence of VUR on
– The needle is slowly withdrawn after delayed VCUG (12 months).
between 0.5 and 2 mL of material has been • This is attributed to several factors including:
injected. – Reabsorption of the injected material
– A second injection may be carried out at – Migration of the injected material
the base of the newly created mound to fur- – Associated dysfunctional voiding
ther elevate the ureteral orifice. • It was shown that on long term, DHA implants
– The bladder is emptied and reinspected. can strongly resemble a stone in the distal ure-
– Any bleeding vessels may be cauterized ter on CT scanning, apparently due to calcifi-
with a Bugbee electrode. cation of the DHA implant.
– Some authors have described an intra- • Persistent vesicoureteral reflux after open
mural injection, in which the distal ure- antireflux surgery:
ter is distended with a jet of saline from – The initial management is a repeat
the cystoscope, allowing the injection injection.
needle to be advanced into the submu- – Many investigators routinely use up to
cosa of the intramural ureter at 6 three separate injections.
o’clock. – Patients who fail multiple injections should
• In general, the success rates with endoscopic be reevaluated and treated for causes of
treatment are significantly lower than those secondary VUR.
reported for open antireflux surgery. – Patients with persistent VUR and in the
• Most studies of endoscopic treatment have presence of a surgical indications for cor-
found that success rates are lower for higher rection of VUR should have open surgery.
grades of vesicoureteral reflux.
• The reported success rate of grade IV VUR
was 63 % after one injection. Bulking Agents Used Endoscopically to
• Polytetrafluoroethylene (Teflon) was used Treat VUR
but concerns over its safety have limited its • Dextranomer and hyaluronic acid
use. (DHA) (Deflux and Zuidex)
• Other bulking agents that have been reported • Polytetrafluoroethylene (Teflon)
include: • Autologous fat
– Autologous fat • Blood
– Blood • Chondrocytes
– Chondrocytes • Bovine collagen
– Bovine collagen • Polydimethylsiloxane
– Polydimethylsiloxane
• The success of endoscopic treatment of VUR • An intravesical approach

are as follows: – The Cohen cross-trigonal technique
– Grades I and II: 78.5 % – The Politano-Leadbetter procedure
– Grade III: 72 % – The Glenn-Anderson repair
– Grade IV: 63 % – Laparoscopic antireflux operation
– Grade V: 51 % – Robotic assisted antireflux operation
• Endoscopic treatment of VUR can be repeated – Endoscopic antireflux surgery
up to three times and this increases the overall • The accepted indications for surgical treat-
success rate to 85 %. ment of VUR include the following:
• The most common complications following – Breakthrough febrile UTIs despite ade-
endoscopic treatment of VUR: quate antibiotic prophylaxis
– Transient ureteral obstruction – Severe reflux (grade V or bilateral grade
– Urinary tract infection IV) that is unlikely to spontaneously
– The success rates at 1 year are significantly resolve, especially if renal scarring is
lower than initial success rates present
– Mild or moderate reflux in females that
persists as the patient approaches puberty,
8.8.4 Surgical Management despite several years of observation
– Poor compliance with medications or sur-
veillance programs
Surgical Treatment of VUR – Poor renal growth or function or appear-
• Open antireflux surgery ance of new scars
– An extravesical approach • The intravesical approach to correct VUR
– The Lich-Gregoire repair depends on the followings:
– Extravesical detrusorrhaphy – Cystoscopy is performed and the bladder
(Hodgson-Zaontz) and ureteral openings are defined.
– An intravesical approach – The bladder is opened anteriorly via a low
– The Cohen cross-trigonal technique abdominal incision.
– The Politano-Leadbetter procedure – The affected ureter or ureters if bilateral
– The Glenn-Anderson repair VUR is present are dissected and separated
• Laparoscopic antireflux operation from their attachments to the bladder mus-
• Robotic assisted antireflux operation cle and connective tissue.
• Endoscopic antireflux surgery – When enough length of the ureter is sepa-
rated, the ureter is pulled across the trigone
through a submucosal tunnel.
• The aim of open, laparoscopic and robotic – The ureteric opening is sutured at the end
assisted antireflux operations is reconstruction of the tunnel to create the necessary 5:1
of the ureterovesical junction to create a ureter length-to-diameter ratio.
lengthened submucosal tunnel for the ureter, • These are the basic principles of the Cohen
which functions as a one-way valve prevent- cross-trigonal technique to treat VUR.
ing backflow of urine into the ureter as the • This is the most popular intravesical technique
bladder fills. used to treat VUR (Fig. 8.48).
• There are several surgical techniques to • The Politano-Leadbetter procedure:
achieve this: – The principle is similar to the Cohen
– Open antireflux surgery technique
• An extravesical approach – The ureter is dissected completely free of
– The Lich-Gregoire repair its attachments and passed through a new
– Extravesical detrusorrhaphy muscular hiatus created higher on the blad-
(Hodgson-Zaontz) der wall.
surgeons to use this technique only for unilat-

eral VUR.
• Extravesical detrusorrhaphy (Hodgson-Zaontz):
– Following the initial dissection, the ureter
is dissected extravesically down to the ure-
terovesical junction.
– The terminal ureter is dissected free from
perivesical tissues except its attachment to the
bladder mucosa which should remain intact.
– Electrocautery is used to incise the bladder
muscle down to the mucosa for a 5-cm arc
around the ureterovesical junction.
– The lateral edges of the incision are under-
mined to create a trough that will form a
new bed for the ureter.
Fig. 8.48 A micturating cystourethrogram showing no – It is important not to open the mucosa of
VUR after anti-reflux surgery
the bladder.
– The ureter is then telescoped into the blad-
– The ureter is then passed down through a der so it courses within a long subepithelial
submucosal tunnel, and the orifice is tunnel.
sutured to the mucosa at its original hiatal – Neither a ureteral stent nor a perivesical
position. drain is needed.
• The Glenn-Anderson repair creates a new – An indwelling Foley catheter is left
ureteral hiatus more distal to the original overnight.
hiatus. • Laparoscopic and robotic assisted repair of
• Extravesical approach: VUR may be possible alternatives to open
– This was developed in an effort to avoid ureteral reimplantation.
the time and morbidity associated with the • Post-operative follow-up:
cystotomy and ureteral anastomosis – Continue prophylactic antibiotics
required for intravesical repair. – A postoperative renal ultrasonography in
– It is particularly useful in patients with uni- 1–2 months.
lateral reflux. – A nuclear cystography in 3 months
– The Lich-Gregoire repair: – Perform interval renal ultrasonography
• The bladder is approached via the annually for 3 years
retroperitoneum. – After confirming resolution of VUR, dis-
• The ureter is dissected from the detrusor continue antibiotic prophylaxis.
muscle, but the orifice is left intact. • Complications due to reimplantation of the
• A narrow furrow in the detrusor muscle ureters occur in less than 1 % of cases, and
is created, down to but not disrupting include the followings:
the mucosa, extending cephalad from – Gross hematuria
the ureteral orifice. – Bleeding in the retroperitoneal space
• The distal ureter is then laid into this – Infections
furrow and the detrusor closed over it. – Ureteral obstruction
• One complication of the extravesical approach – Injury to adjacent organs
is postoperative urinary retention, which gen- – Persistent reflux
erally resolves spontaneously. – Recurrent UTIs despite antireflux surgery
• Rare reports of permanent voiding dysfunc- • Gross hematuria:
tion and retention in patients undergoing bilat- – Gross hematuria after ureteral reimplanta-
eral extravesical procedures have led some tion is common.
– Persistent bleeding or clots indicate • Edema at the ureteroneocystostomy site

inadequate hemostasis at the time of • Intraureteral blood clots
operation. • Intraureteral mucous
– Hematuria is often self-limited and does • Bladder spasms
not require operative intervention. • Submucosal bladder hematoma
– Continue prolonged catheterization is – Rarely, the obstruction is severe and pres-
important until hematuria resolves. ent late, 1–2 weeks postoperatively.
– Patients rarely need transurethral fulgura- – This is usually secondary to ischemia of
tion or reoperation. the distal reimplanted segment of the ureter
• Persistent, transient, contralateral reflux: leading to fibrosis and stricture, an incor-
– Persistent reflux of the reimplanted ureter rect tunnel construction or too tight ureteral
and development of de novo reflux of the hiatus.
contralateral side are usually temporary – These patients present with flank or abdom-
and resolve spontaneously. inal pain, nausea, and vomiting.
– Transient postoperative reflux is usually – Obtain a renal ultrasonography, intrave-
caused by detrusor instability of the heal- nous pyelography, or nuclear renography
ing bladder. to confirm diagnosis.
– Persistent reflux of the ipsilateral ureter in – Ultrasonography can be difficult to assess
the absence of secondary causes (e.g. a in patients who had significant dilation
poorly compliant bladder) is usually caused preoperatively.
by a technical error. – Rarely, the obstruction is intermittent due
– Some technical problems associated with to kinking or angulation of the reimplanted
ureteral reimplantation include: ureter with bladder filling.
• Inadequate ureteral mobilization – Most postoperative ureteral obstructions
• Short intramural tunnel resolve spontaneously; however, tempo-
• Inadequate anchoring of the ureter rary ureteral stenting may be necessary.
• Inappropriate placement of the ureteral – Cystoscopy, ureteroscopic dilation and
orifice stent placement may correct mild obstruc-
– These technical errors are treated by reop- tion or stenosis.
eration or endoscopic injection if the reflux – Percutaneous placement of a nephrostomy
is grade III or less. tune may be necessary if a transvesical
– Most contralateral reflux is caused by approach is not achievable.
recurrent or previously undiagnosed reflux. – Treatment for high-grade obstruction is
– Contralateral reflux may become evident surgical revision of the obstructed system.
when the contralateral refluxing ureter is
no longer refluxing. These can managed
conservatively, and usually subside 8.9 Mortality/Morbidity
spontaneously.
– If a patient experiences persistent or severe • Modern series consistently report success
VUR following repair, perform a thorough rates greater than 95 % for antireflux surgery.
workup, including urodynamics, imaging, • In cases in which reflux persists postopera-
and cystoscopy. tively, initial observation with continued anti-
• Postsurgical obstruction after open antireflux biotic prophylaxis is indicated.
surgery: • A substantial number of patients with reflux at
– Most cases of postoperative upper tract the first postoperative study have complete
obstruction are mild, produce no symp- resolution at the 1-year follow-up point.
toms, and spontaneously resolve. • Reoperation is generally reserved for patients
– These cases are due to: with persisted febrile UTI despite prophylaxis.
Further Reading 269
• A very high percentage of patients in whom • It is estimated that 15–30 % of renal

surgery has failed have voiding dysfunction, failure in children and young adults is
thus urodynamic evaluation should be attributed to chronic pyelonephritis and
considered in these patients, especially if reflux nephropathy.
reoperation is considered. • Although renal failure is a devastating
• New contralateral vesicoureteral reflux after complication of vesicoureteral reflux, it
unilateral antireflux surgery: actually affects only a small minority of
– New onset of vesicoureteral reflux in a children with VUR.
renal unit that had no vesicoureteral reflux
on preoperative imaging occurs in 10–32 %
of patients after open correction and Further Reading
7–14 % of patients after endoscopic
correction. 1. Asgari SA, Asl AS, Safarinejad MR, Ghanaei
MM. High success rate with new modified endoscopic
– In general, the new vesicoureteral reflux is
treatment for high-grade VUR: a pilot study with pre-
usually of low grade and more likely to liminary report. J Pediatr Urol. 2015;12(2):100.e1–4.
spontaneously resolve. 2. Beetz R, Mannhardt W, Fisch M, Stein R, Thüroff JW.
• Outcome and morbidity of VUR: Long-term followup of 158 young adults surgically
treated for vesicoureteral reflux in childhood: the
– The success rate of ureteral reimplantation
ongoing risk of urinary tract infections. J Urol.
is higher than 95 %. 2002;168(2):704–7; discussion 707.
– The success rate of endoscopic treatment is 3. Belman AB. Vesicoureteral reflux. Pediatr Clin North
lower than open surgical treatment but Am. 1997;44(5):1171–90.
4. Canning DA. Five-year study of medical or surgical
offers an alternative to either medical treat-
treatment in children with severe vesico-ureteral
ment or open surgical treatment. reflux. Dimercaptosuccinic acid findings. J Urol.
– Following surgical repair, the incidence of 2000;163(1):380.
pyelonephritis significantly decreases in 5. Cooper CS, Chung BI, Kirsch AJ. The outcome of
stopping prophylactic antibiotics in older children with
comparison to medical management with
vesicoureteral reflux. J Urol. 2000;163(1):269–72.
long-term antibiotic therapy. 6. Elder JS, Diaz M, Caldamone AA, Cendron M,
– The incidence of cystitis or renal scarring Greenfield S, Hurwitz R. Endoscopic therapy for vesi-
is the same following both medical and sur- coureteral reflux: a meta-analysis. I. Reflux resolution
and urinary tract infection. J Urol. 2006;175(2):
gical management of VUR.
716–22.
• Morbidity associated with vesicoureteral 7. Elder JS, Diaz M, Caldamone AA, et al. Endoscopic
reflux: therapy for vesicoureteral reflux: a meta-analysis.
– Acute urinary tract infection I. Reflux resolution and urinary tract infection. J Urol.
2006;175(2):716–22.
– Reflux nephropathy
8. Hayn MH, Smaldone MC, Ost MC, Docimo SG.
– Changes in renal function: Minimally invasive treatment of vesicoureteral reflux.
• Decrease in urine-concentrating ability Urol Clin North Am. 2008;35(3):477–88, ix.
• Decrease in glomerular filtration rate 9. Hoberman A, Charron M, Hickey RW, et al. Imaging
studies after a first febrile urinary tract infection in
– Decreased renal and somatic growth
young children. N Engl J Med. 2003;348:195.
– Hypertension 10. Hoberman A, Greenfield SP, Mattoo TK, Keren R,
• Reflux nephropathy may be the most com- Mathews R, Pohl HG, et al. Antimicrobial prophy-
mon cause of childhood hypertension. laxis for children with vesicoureteral reflux. N Engl
J Med. 2014;370(25):2367–76.
• This is secondary to elevated renin lev-
11. Keren R, Shaikh N, Pohl H, et al. Risk factors for
els produced by scarred renal tissue recurrent urinary tract infection and renal scarring.
• The presence of hypertension correlates Pediatrics. 2015;136:e13.
well with the degree of renal scarring. 12. Kirsch AJ, Perez-Brayfield M, Smith EA, Scherz HC.
The modified sting procedure to correct vesicoure-
– Renal failure
teral reflux: improved results with submucosal
• The most devastating outcome of reflux implantation within the intramural ureter. J Urol.
nephropathy is renal failure. 2004;171(6 Pt 1):2413–6.
13. Lee YJ, Lee JH, Park YS. Risk factors for renal scar 20. Peters CA, Skoog SJ, Arant Jr BS, et al. Summary of
formation in infants with first episode of acute pyelo- the AUA guideline on management of primary vesico-
nephritis: a prospective clinical study. J Urol. ureteral reflux in children. J Urol. 2010;184:1134.
2012;187(3):1032–6. 21. RIVUR Trial Investigators, Hoberman A, Greenfield
14. Mattoo TK, Chesney RW, Greenfield SP, Hoberman SP, et al. Antimicrobial prophylaxis for children with
A, Keren R, Mathews R, et al. Renal scarring in the vesicoureteral reflux. N Engl J Med. 2014;370:
Randomized Intervention for Children with 370–2367.
Vesicoureteral Reflux (RIVUR) trial. Clin J Am Soc 22. Shaikh N, Ewing AL, Bhatnagar S, Hoberman A. Risk
Nephrol. 2015;11:54. of renal scarring in children with a first urinary tract
15. Mattoo TK, Chesney RW, Greenfield SP, et al. Renal infection: a systematic review. Pediatrics. 2010;
scarring in the Randomized Intervention for Children 126:1084.
with Vesicoureteral Reflux (RIVUR) trial. Clin J Am 23. Sjöström S, Sillén U, Jodal U, et al. Predictive factors
Soc Nephrol. 2016;11:54. for resolution of congenital high grade vesicoureteral
16. Metcalfe CB, Macneily AE, Afshar K. Reliability reflux in infants: results of univariate and multivariate
assessment of international grading system for vesi- analyses. J Urol. 2010;183:1177.
coureteral reflux. J Urol. 2012;188:1490. 24. Smellie JM, Prescod NP, Shaw PJ, et al. Childhood
17. Nagler EV, Williams G, Hodson EM, Craig JC. reflux and urinary infection: a follow-up of 10–41 years
Interventions for primary vesicoureteric reflux. in 226 adults. Pediatr Nephrol. 1998;12(9):727–36.
Cochrane Database Syst Rev. 2011;(6):CD001532. 25. Tekgül S, Riedmiller H, Hoebeke P, et al. EAU guide-
18. Nelson CP, Johnson EK, Logvinenko T, Chow JS. lines on vesicoureteral reflux in children. Eur Urol.
Ultrasound as a screening test for genitourinary 2012;62:534.
anomalies in children with UTI. Pediatrics. 2014; 26. Weiss R, Duckett J, Spitzer A. Results of a random-
133:e394. ized clinical trial of medical versus surgical manage-
19. Nelson CP, Johnson EK, Logvinenko T, Chow JS. ment of infants and children with grades III and IV
Ultrasound as a screening test for genitourinary primary vesicoureteral reflux (United States). The
anomalies in children with UTI. Pediatrics. 2014; International Reflux Study in Children. J Urol.
133(3):e394–403. 1992;148(5 Pt 2):1667–73.
Pediatric Urolithiasis
9
9.1 Introduction • The endemic calculi observed in developing

nations are often confined to the bladder and
• Urolithiasis (from Greek oûron, “urine”, + comprise predominantly ammonium acid,
lithos, “stone”, + -iasis) are calculi formed or urate, and uric acid, and seem to correlate with
located anywhere in the urinary system. a decreased availability of dietary phosphates.
• It comprises: • Most calculi in the United States are found in
– Nephrolithiasis (the formation of kidney the kidneys or ureters. They are composed of
stones) either calcium oxalate or calcium phosphate,
– Ureterolithiasis (the formation of stones in and often associated with a metabolic
the ureters) abnormality.
– Cystolithiasis (the formation of bladder • The exact incidence of urolithiasis in child-
stones) hood is not known but it is believed to be
• Nephrocalcinosis refers to increased calcium approximately 10 % of that in adults, which is
content in the parenchyma of the kidney. around 5 % in developed countries.
• Urolithiasis is a fairly common disease in • Urolithiasis in childhood differs substantially
adults with an estimated prevalence of 3–5 %. from that in adults with regard to:
• Urolithiasis has been regarded as an uncom- – Etiology
mon condition in children. – Clinical features
• Childhood urolithiasis however, is an increas- – Diagnostic techniques
ingly recognized condition. – Treatment.
• The estimated incidence in the United States • Approximately 40 % of children with uroli-
from the 1950s to the 1970s is approximately thiasis have a positive family history of kidney
1–2 % that of adults. More recent studies from stones.
the United States suggest an increase in the inci- • Most of the children with urolithiasis have an
dence and prevalence of childhood urolithiasis, underlying metabolic etiology.
with one study demonstrating a nearly fivefold • Materials that produce stones in the urinary
increase in the incidence in the last decade. tract of children include the following:
• Calculi are particularly uncommon in children – Calcium with phosphate or oxalate
of African descent. – Purine derivatives
• In certain regions, such as Southeast Asia, the – Magnesium ammonium phosphate
Middle East, India, and Pakistan, calculi are (struvite)
endemic. – Cysteine

272 9 Pediatric Urolithiasis
– Combinations of the above items – The drug may increase the concentration of
– Drugs or their metabolites (e.g., phenytoin, stone-forming minerals by increasing the
triamterene) filtered load or decreasing the tubular
– Melamine-contaminated milk powder reabsorption.
consumption • Anticancer agents increase the filtered
load of uric acid.
• Glucocorticoids increase the filtered
9.2 Etiology load of calcium.
• Allopurinol increases the filtered load of
• The development of urinary stones depends xanthine in patients with tumor lysis to
on the following three factors: produce xanthinuria.
– Supersaturation of stone-forming compo- • Furosemide decreases tubular calcium
nents in urine reabsorption, leading to increased urine
– The presence of chemical or physical stim- calcium concentration.
uli in urine that promote stone formation – The drug may alter urine pH, decreasing
– Inadequate amount of chemicals in urine the solubility of a stone-forming agent.
that inhibit stone formation (e.g., magne- • In children with distal renal tubular aci-
sium, citrate) dosis, bicarbonate probably contributes
• The followings are contributing factors to uri- to stone formation by further alkaliniz-
nary stones developments: ing the urine.
– Dietary factors • Fluid intake quantitatively and qualitatively is
– A high oxalate intake may contribute to an important factor for the development of
calcium oxalate stone production. urolithiasis.
– Excessive purine intake may contribute to – A low fluid intake leads to concentrated urine
the production of stones containing uric and increases the risk of stone formation.
acid and uric acid plus calcium stones. – Water may have a high mineral content in
– A ketogenic diet, prescribed to reduce sei- some areas.
zures, places children at risk for both uric – Milk contains significant calcium and vita-
acid and calcium stone formation. min D.
• The development of calcium urolithiasis is – Orange juice may be supplemented with
attributed to by increased urinary calcium. calcium.
• Urinary calcium increases: – Tea contains oxalate and often sucrose.
– With increased dietary calcium intake. – Many drinks (e.g., sports drinks) contain
– With increased sodium chloride intake. sodium chloride and sucrose.
– Severe dietary phosphate restriction • Several diseases, or the medications used to
increases urine calcium excretion. treat them, increase the risk of urolithiasis
– A diet high in protein from animal sources, development. These include:
glucose or sucrose increases urinary calcium. – Distal renal tubular acidosis
– Vitamins A and D can contribute to calcium – Short-bowel syndrome
urolithiasis when taken in excessive amounts. – Inflammatory bowel disease
– Fructose consumption is also associated – Intractable seizures
with an increased risk of kidney stones. – Cystic fibrosis
• Drugs taken by the patients may contribute to • Urolithiasis is also a known complication follow-
the development of urolithiasis for the following renal transplant for the following reasons:
ing reasons: – Retention of suture material
– The drug or its metabolites may precipitate – Recurrent urinary tract infection
as stones (e.g., phenytoin, triamterene, – Hypercalciuria
sulfadiazine, felbamate, ceftriaxone). – Urinary stasis
9.2 Etiology 273
• Gastrostomy tube–fed children are at higher • The major metabolic abnormalities associated
risk of urolithiasis for the following reasons: with urolithiasis include:
– The concomitant use of Topiramate – Hypercalciuria
(an anticonvulsant) – Hyperoxaluria
– Urinary tract infection – Hypocitraturia
– Subclinical chronic dehydration – Cystinuria
• Risk factors for pediatric urolithiasis include – Hyperuricosuria
the following: • Hypercalciuria or hypocitraturia are the most
– Habitually low urine volume frequently reported abnormalities in children.
– High urine excretion of calcium • In the United States the chemical composition
– High urine excretion of uric acid of urolithiasis is as follows:
– High urine excretion of oxalate – 40–65 % are calcium oxalate
– Low urine pH: Uric acid and cysteine are – 14–30 % are calcium phosphate
less soluble in acid urine. – 10–20 % are struvite (magnesium ammo-
– High urine pH: Struvite and calcium nium phosphate)
phosphate are less soluble in alkaline – 5–10 % are cysteine
urine. – 1–4 % are uric acid
– Nidus for crystal precipitation • Rarely, stones may also comprise xanthine, or
• In children, hypercalciuria is a significant risk 2, 8-dihydroxyadenine.
factors for urolithiasis. • Metabolic abnormalities known to be associ-
• Other risk factors for urolithiasis include: ated with increased risk for urolithiasis include:
– Developmental abnormalities of the uri- • Hypercalciuria
nary tract – Hypercalciuria is formally defined as cal-
– Urinary obstruction cium excretion of greater than 4 mg/kg/day
– Urinary stasis in children older than 2 years.
– Urinary tract infection with urea-splitting – Hypercalciuria is found in approximately
microorganisms 30–50 % of children with urolithiasis.
• Functional or anatomic obstruction predis- – The most common cause in children and
poses children to stone formation by promot- adults is idiopathic hypercalciuria.
ing stasis of urine and infection. – Idiopathic hypercalciuria is defined as
• Only 1–5 % of children with urologic abnor- hypercalciuria that occurs in the absence of
malities develop calculi, suggesting a con- hypercalcemia in patients in whom no
comitant metabolic abnormality in patients other cause can be identified.
with both urologic abnormalities and – Familial idiopathic hypercalciuria appear
calculi. to be transmitted in an autosomal dominant
• Although infection is commonly associated fashion with incomplete penetrance.
with kidney stones, it is unlikely to be caus- – Approximately 4 % of asymptomatic
ative of non–struvite calculi. healthy children demonstrate evidence of
• Genitourinary anomalies are found in approx- idiopathic hypercalciuria, and 40–50 % of
imately 30 % of children with urolithiasis. those children have a positive family his-
These include: tory of urolithiasis.
– Hydronephrosis – In school-aged children, a calcium to cre-
– Duplex ureter atinine ratio of 0.2 mg/mg or less is consid-
– Posterior uretheral valves ered normal, although higher values are
– Bladder exstrophy reported in younger children.
• Urolithiasis is associated with an identifiable – When hypercalciuria is observed, several con-
metabolic abnormality in approximately ditions must be excluded before establishing a
40–50 % of children. diagnosis of idiopathic hypercalciuria.
– In children with hypercalcemic hypercalci- – Severe polyhydramnios, prematurity, and

uria, the following possibilities should be occasionally sensorineural deafness are the
excluded: hallmark features.
• Hyperparathyroidism – There are four types of Bartter syndrome
• Hypervitaminosis D deepening on the mutation.
• Prolonged immobilization – Mutations in the SLC12A, KCNJ1, and
• Sarcoidosis BSND genes (Bartter syndrome type I, type
• Malignancy II, and type IV, respectively) typically result
• Juvenile idiopathic arthritis in severe dysfunction of the thick ascending
• Corticosteroid excess limb of the loop of Henle in the neonatal
• Adrenal insufficiency period (neonatal Bartter syndrome).
• William syndrome – Mutations in the ClCKB gene (Bartter syn-
– In children with hypocalcemic hypercalci- drome type III) usually cause milder
uria, the following possibilities should be dysfunction of the thick ascending limb of the
excluded: loop of Henle and often present outside the
• Hypoparathyroidism neonatal period (classic Bartter syndrome).
• Autosomal, dominant hypocalcemic • Familial hypomagnesemia with hypercalci-
hypercalciuria uria and nephrocalcinosis (FHHNC):
– Other causes of hypercalciuria include: – FHHNC is an autosomal recessive condi-
• Idiopathic hypercalciuria tion caused by mutations in either the
• Prematurity CLDN-16 or CLDN-19 genes.
• Diuretics (furosemide and acetazolamide) – FHHNC often presents in childhood with sei-
• Anticonvulsants (topiramate and zures or tetany caused by hypomagnesemia.
zonisamide) – Other clinical manifestations include fre-
• Ketogenic diet quent urinary tract infections (UTI), polyuria,
• Dent disease polydipsia, failure to thrive, nephrolithiasis,
• Bartter syndrome and progressive renal failure.
• Familial hypomagnesemia with hyper- – Homozygous CLDN-16 or -19 mutations
calciuria and nephrocalcinosis (FHHNC) are associated with impaired tight junction
• Distal renal tubular acidosis (dRTA) integrity in the thick ascending limb of the
• Hereditary hypophosphatemic rickets loop of Henle, urinary magnesium and cal-
with hypercalciuria (HHRH) cium wasting, and hypomagnesemia.
• Medullary sponge kidney – Patients usually develop the characteristic
• Dent disease: triad of hypomagnesemia, hypercalciuria,
– This is an X-linked inherited condition and nephrocalcinosis.
caused by a mutation in the CLCN5 gene. – Profound visual impairment characterized
– The condition is characterized by low- by macular coloboma, significant myopia,
molecular-weight proteinuria, nephrocalci- and horizontal nystagmus can been seen in
nosis, normocalcemic hypercalciuria, association with CLDN-19 mutations.
nephrolithiasis, and chronic kidney disease. • Distal renal tubular acidosis (dRTA):
• Bartter syndrome: – Primary dRTA is an inherited condition
– This is an autosomal recessive condition characterized by systemic acidosis as a
characterized by renal salt wasting, hypo- result of the inability of the distal tubule to
kalemia, metabolic alkalosis, hypercalci- adequately acidify the urine.
uria, and normal serum magnesium levels. – Failure to thrive, polyuria, polydipsia, hyper-
– Children younger than 6 years typically pres- calciuria, hypocitraturia, nephrocalcinosis,
ent with salt craving, polyuria, dehydration, renal calculi, and hypokalemia are common
emesis, constipation, and failure to thrive. presenting signs in infancy.
9.2 Etiology 275
– Primary dRTA may be a dominant (SLC4A1 • Or, more commonly, as a secondary

gene) or a recessive condition (ATP6V1B1 phenomenon caused by increased oxa-
or ATP6V0A4 genes). late absorption or excessive intake of
– The inability to secrete H+ ions from the oxalate precursors.
α-intercalated cells of the distal tubule is – Primary hyperoxaluria (PH):
caused by either a defective vacuolar H+- • PH type I and II are relatively rare, auto-
ATPase (ATP6V1B1 or ATP6V0A4 genes) somal recessive disorders of endoge-
or a defective Cl−/HCO3− anion exchanger-1 nous oxalate production.
(SLC4A1 gene). • Overproduction of oxalate by the liver
– Sensorineural hearing loss may be found in causes excessive urinary oxalate excre-
patients with ATP6V1B1 mutations. tion with resultant nephrocalcinosis and
• Hereditary hypophosphatemic rickets with nephrolithiasis.
hypercalciuria (HHRH): • The calcium oxalate deposition results in
– HHRH is a rare, autosomal recessive disor- progressive renal damage; however, the
der caused by mutations in the SLC34A3 clinical presentation can vary from end-
gene, resulting in loss-of-function of the stage renal failure in the neonate to occa-
type IIc sodium phosphate cotransporters sional stone passage into adulthood.
of the proximal tubule. • Because of the clinical variability, the
– The decreased renal phosphate reabsorption diagnosis is often overlooked and only
can result in profound hypophosphatemia, realized after the loss of a transplanted
normocalcemia, rickets, and bone pain. kidney.
– Hypercalciuria and nephrolithiasis are also • PH type I is caused by mutations in the
commonly observed and may be the result AGXT gene, which result in a functional
of a hypophosphatemia-induced stimulation defect of the hepatic peroxisomal
of 1, 25-dihydroxyvitamin D synthesis. enzyme alanine–glyoxylate aminotrans-
– The increased synthesis causes increased ferase (AGT).
gastrointestinal absorption of calcium and • The deficit leads to accumulation of gly-
excessive urinary calcium losses in the face oxylate, glycolate, and oxalate in the
of normal serum calcium levels. urine.
• Hyperoxaluria: • Pyridoxine is an essential cofactor for
– Oxalate is an end product of the metabolic proper AGT activity and, rarely, pro-
pathways for glyoxylate and ascorbic acid found vitamin B6 deficiency can mimic
and is primarily excreted by the kidneys. PH type I.
• The vast majority (80–85 %) of daily • PH type II is caused by mutations in the
urinary oxalate excretion is derived GRHPR gene with resultant deficient
from normal metabolic homeostasis. glyoxylate reductase–hydroxypyruvate
• The remainder (10–15 %) is from reductase enzyme activity.
dietary intake. • Excessive amounts of oxalate and
– Daily urine oxalate excretion is generally l-glyceric acid are excreted by the kidney.
less than 50 mg/day/1.73 m2 of body sur- • PH type II is somewhat milder com-
face area. pared with PH type I but is not benign.
– The random urine oxalate to creatinine • Recently, a third variant, PH type III has
ratio can be used to estimate oxalate been described in eight families with
excretion. hyperoxaluria and mutations in the
– Increased urinary oxalate excretion may be DHDPSL gene.
caused: • The exact mechanism by which hyper-
• By an inherited metabolic disorder (pri- oxaluria occurs in PH type III is yet to
mary hyperoxaluria [PH]). be fully elucidated.
– Secondary hyperoxaluria: • Distal renal tubular acidosis (dRTA)

– Secondary hyperoxaluria is caused by: • Chronic diarrhea
• A dietary exposure to large amounts – Given that an incomplete dRTA can occur
of oxalate (or oxalate precursors). in the absence of an overt systemic acidosis
• An underlying disorder that causes or hypokalemia, the condition can often be
increased absorption of dietary overlooked in the face of hypocitraturia if
oxalic acid from the intestinal tract. provocative acid-load testing is not readily
– Gastrointestinal absorption varies inversely available.
with dietary calcium intake, and, as a – Despite these known associations, most
result, calcium-deficient diets may increase cases of hypocitraturia are idiopathic
oxalate absorption and hyperoxaluria. although a diet rich in animal protein and
– Oxalate is a byproduct of ascorbic acid low in vegetable fiber and potassium seems
metabolism, and high doses of vitamin to promote lower citrate excretion.
C have also been associated with • Cystinuria:
hyperoxaluria. – Cystinuria is an autosomal recessive disor-
– Increased dietary absorption is usually der caused by mutations in either the
characterized by fat malabsorption or SLC3A1 or the SLC7A9 genes.
chronic diarrhea. – The end result is a disordered amino acid
– Other causes of secondary hyperoxal- transport in the proximal tubule.
uria include: – Cystinuria is characterized by urinary
• Inflammatory bowel disease hyperexcretion of cystine and the dibasic
• Celiac disease amino acids lysine, ornithine, and arginine.
• Exocrine pancreatic insufficiency – Normal individuals excrete less than
(cystic fibrosis) 50–60 mg of cystine/day/1.73 m2 of body
• Biliary tract disease surface area, whereas patients who are
• Small bowel resection or short bowel homozygous for cystinuria often excrete
syndrome greater than 400 mg/day/1.73 m2 of body
– The pathogenesis in these conditions surface area.
results from the presence of free fatty – Patients typically present with renal colic
acids that bind calcium in the intestinal and urolithiasis in the second or third
lumen resulting in more unbound oxa- decade of life; however, they may present
late, which is free to be absorbed. as early as infancy with staghorn calculi.
• Hypocitraturia: – The poor solubility of cystine in the urine
– Citrate is normally present in the urine and causes precipitation in the collecting sys-
regulated through a process of both absorp- tem, which, if left untreated, usually results
tion and metabolism at the level of the in recurrent episodes of calculi and long-
proximal tubule. term risk for renal failure.
– Hypocitraturia is generally defined as a – Associated urinary tract infections are
citrate to creatinine ratio of less than common, and combined cystine and stru-
180 mg/gm in men and less than 300 mg/ vite calculi have been reported.
gm in women on a 24-h urine collection. – In cystinuria, the disordered cystine trans-
– Intracellular acidosis of the proximal port primarily results from dysfunction of
tubule, caused by either metabolic acidosis the heteromeric amino acid transporter
or hypokalemia results in an increased (rBAT/b0,+AT), comprising heavy (rBAT)
citrate absorption in the proximal tubule and light (b0,+AT) subunits.
and resultant hypocitraturia. – Cystinuria was originally classified into
– Hypocitraturia results from: type I and non–type I (types II and III)
• Ketogenic diet based on the urinary cystine concentration
• Certain medications (topiramate, pattern of obligate heterozygotes and the
zonisamide, and acetazolamide) presumed mode of inheritance.
9.2 Etiology 277
– Type I follows the classic autosomal reces- • Cystinuria type C: Patients who have a
sive inheritance with heterozygotes show- mutation in both the SLC3A1 and
ing normal cystine excretion. SLC7A9 genes.
– In contrast, non–type I (type II and III) het- • Hyperuricosuria:
erozygotes demonstrate moderate or high – Uric acid excretion is greater in children
excretion of urinary cystine. than in adults, with the highest urinary
– Types II and III differ in that type III homo- fractional excretion (Fe) found in neo-
zygotes show a nearly normal increase in nates (Fe 30–50 %) and levels reaching
cystine plasma levels after oral cystine adult values (Fe 8–12 %) in adolescence.
administration. – Hyperuricosuria is defined as uric acid
– It is now clear that homozygous mutations excretion of greater than 815 mg/
in the SLC3A1 gene, which encodes rBAT day/1.73 m2 of body surface area.
is associated with type I cystinuira, and – When adjusted for glomerular filtration
homozygous mutations in the SLC7A9 rate (GFR), relative uric acid excretion is
gene, which encodes b0,+AT accounts for fairly constant after 2 years of age.
most cases of type II and III. – In children who are not yet trained to use
– A more recent classification system has toilet but older than of 2 years, hyperuri-
been developed: cosuria can be defined as greater than
• Cystinuria type A: Patients who are 0.56 mg/dL of GFR on a spot urine
homozygous for the SLC3A1 mutations. collection.
• Cystinuria type B: Patients who are – This value may be calculated using
homozygous for the SLC7A9 mutations Equation:
• Urine uric acid ( mg / dL ) ´ Plasma creatinine ( mg / dL ) / Urine creatinine ( mg / dL ) .
– Hyperuricosuria in the setting of low uri- • Uricosuric medications (probenecid,

nary pH is the greatest risk factor for uric salicylates, and losartan)
acid stone formation. • Cyanotic congenital heart disease
– Hyperuricosuria associated with significant • Melamine toxicity
hyperuricemia is usually associated with: • Idiopathic (familial) hyperuricosuria
• Inherited disorders of purine – There is also a phenomenon primarily
metabolism observed in adults called hyperuricosu-
• Lymphoproliferative disorders ric calcium oxalate urolithiasis in
• Polycythemia which hyperuricosuria seems to be the
– Rarely, a condition known as hereditary principle contributor to the develop-
renal hypouricemia characterized by low ment of calcium oxalate stones with
serum uric acid, hyperuricosuria, nephroli- either no or minimal uric acid content
thiasis, and exercise-induced acute renal (epitaxy).
failure has been reported. • Inherited disorders of purine metabolism:
– Mutations in either the SLC22A12 or the – Phosphoribosyl pyrophosphate synthetase
SLC2A9 genes, both of which encode urate superactivity (PRPSS):
transporters expressed in the proximal • This is an X-linked condition caused by
tubule, are known to be causative factors of mutations in the PRPS1 gene.
hyperuricosuria. • The overactive PRPSS is associated
– Other causes of hyperuricosuria include: with excessive purine production.
• Excessive purine intake (animal protein, • The subsequent purine degradation
anchovies, and mussels) results in hyperuricemia, gout, hyperuri-
• Hemolysis cosuria, and uric acid nephrolithiasis.
• Some affected individuals have neuro- • Upper urinary calculi associated with urease-
developmental abnormalities, particu- producing bacterial infection occur in England
larly sensorineural deafness. and Europe.
– Hypoxanthine-guanine phosphoribosyl • In children, calcium stones are most common.
transferase (HPRT) deficiency: • In children urolithiasis occur with almost
• This is an X-linked inborn error of equal frequency among boys and girls. The
purine metabolism caused by mutations boy-to-girl ratio is 3:2.
in the HPRT1 gene associated with • Urinary stones are typically classified by their
overproduction of uric acid. location or by their chemical composition.
• Complete deficiency of HPRT activity • Urinary stones are classified according to their
is associated with the Lesch-Nyhan location as follows:
syndrome, characterized by mental – Renal
retardation, spastic cerebral palsy, cho- – Ureteric
reoathetosis, uric acid calculi, and self- – Vesical
injurious behavior. – Urethral
• Children with partial HPRT deficiency can • Urinary stones are classified according to their
be phenotypically similar to patients with chemical composition as follows:
complete deficiencies or may have more – Calcium-containing
subtle or mild neurologic symptoms. – Struvite
• Renal stones, uric acid nephropathy, – Uric acid
renal obstruction, or gout may be the – Other compounds
first presenting signs of the disease. • Calcium oxalate is a major constituent of most
urinary stones.
• Knowledge of composition of urinary stones
9.3 Classification of Urolithiasis is important as this may help to design preven-
tive therapy.
• Urolithiasis are considered relatively rare in • The approximate frequency of kidney stone
children. types in the pediatric age group is:
• In Europe, kidney stones occur in one to two – Calcium with phosphate or oxalate (57 %)
children per million population per year. – Struvite (24 %)
• This however is not the case nowadays and a – Uric acid (8 %)
significant increase in the number of children – Cystine (6 %)
diagnosed with and treated for urolithiasis has – Endemic (2 %)
occurred in the last decade. – Mixed (2 %)
• Children with stones now account for 1 in 685 – Other types (1 %).
pediatric hospitalizations in the United States. • With children, particularly younger children,
• Surprisingly, more than half the patients are the primary cause of stone formation (e.g.,
younger than 13 years at hospitalization. hypercalciuria, hyperuricosuria) can usually
• In underdeveloped countries, children more be identified with a thorough evaluation.
frequently have endemic bladder stones than
renal stones.
• Endemic bladder calculi are common in devel- 9.4 Clinical Features
oping countries where dietary protein is
mostly derived from plant sources rather than • The clinical manifestations of urolithiasis
meat. These areas include: depends on the following factors:
– Eastern Europe – The size of the stone
– Southeast Asia – The location of the stone
– India – The production of urinary outflow
– The Middle East obstruction
– The movement of the stone – Several inherited disorders in purine

– The presence of infection metabolism lead to uric acid stones (Lesch-
• Larger stones tend to be more symptomatic, Nyhan disease is probably the best known).
although some large stones produce few • The clinical presentation of urolithiasis are
symptoms. variable and include:
• Sometimes small stones produce severe symp- – Symptoms differ according to the location
toms as a result of their movement. of the stone.
• History should include questions to identify: – Intense pain that suddenly occurs in the
– Frequent urinary tract infections back and radiates downward and centrally
– Frequent bouts of abdominal pain toward the lower abdomen or groin.
– Hematuria (gross or microscopic) – The pain may be dull aching localized to
– Passage of previous calculus the renal area or lower abdomen in those
– Dietary intake (e.g., oxalate, purine, cal- with urinary bladder stones.
cium, phosphate, fructose, animal protein) – The pain may be nonspecific localized to
– Drug intake (e.g., anticancer drugs, gluco- the abdomen, flank, or pelvis.
corticoids, allopurinol, loop diuretics) – Sometimes the pain is severe colicky local-
– Vitamin intake (A, D) ized to the flanks, abdomen or pelvis or
– Fluid intake, habitual fluid type (e.g., water, radiates from the flank downwards towards
milk, tea, sports drinks), the urinary bladder and urethra.
• History should include questions to identify – In infants and children and because of rar-
chronic disease: ity of urolithiasis, the pain may be attrib-
– Renal tubular acidosis uted to intestinal colic.
– Inflammatory bowel disease – Hematuria, usually gross, occurring with
– Short-gut syndrome or without pain.
– Intractable seizures – Hematuria may or may not be present or
– Cystic fibrosis may be microscopic.
– Prior urologic surgery (e.g., kidney – Macroscopic or microscopic hematuria can
transplant) occur in up to 90 % of children with
– Recent immobilization urolithiasis.
• A careful family history to identify other fam- – Urinary tract infection may be the first pre-
ily members with stones is important. sentation of urolithiasis.
– In some reports, as many as 70 % of chil- – Unexplained sterile pyuria or recurrent uri-
dren with idiopathic hypercalciuria have a nary tract infections (UTIs) should raise
family history of stones. The cause of idio- the level of suspicion for urolithiasis, espe-
pathic hypercalciuria is unknown, but it cially in the younger child.
may be transmitted as an autosomal domi- – Urolithiasis may be discovered incidentally
nant trait. during radiological investigation of chil-
• Other inherited conditions to be considered dren with urinary tract infection.
during evaluation include: – Asymptomatic urolithiasis may be discov-
– Cystinuria, an autosomal recessive defect ered during radiological investigation for
of amino acid transport that leads to cystine another reason.
kidney stones. – Persistent microscopic hematuria, which
– Glycinuria, a rare inherited renal tubular consists of five or more RBCs per high-
defect producing oxalate stones. power field in three of three consecutive
– Xanthinuria, an autosomal recessive disor- centrifuged urine specimens obtained at
der that produces xanthine urolithiasis. least 1 week apart may be the presentation
– Primary hyperoxaluria, produced by an of urolithiasis in children.
autosomal disorder leading to oxalate – Ureteral stones are much more likely to
stones. cause obstruction that leads to severe
colicky or non-specific flank or abdominal • Estimating the ratio of calcium, uric acid, oxa-
pain. late, cystine, citrate, and magnesium to
– Renal stones may be found incidentally creatinine.
and remain present for years without caus- • A 24-h urine collection for calcium, phospho-
ing symptoms. rus, magnesium, oxalate, uric acid citrate, cys-
– Approximately 10 % of calculi can present tine, protein, and creatinine clearance.
with fever, dysuria and urinary frequency • Renal ultrasonography is very effective for
and are usually localized to the lower uri- identifying stones in the urinary tract.
nary tract. • Generally, ultrasonography should be used as
– Urolithiasis may also be complicated by a first study.
urinary tract infection. These patients may – US remains the initial study of choice in
be asymptomatic or present with dysuria the assessment of calculi in children.
and frequency. Pyuria may also be present – Ultrasound has the ability to detect 90 % of
without bacteriuria or infection. calculi confined to the kidney.
– Rarely, a urethral stone can present with – The sensitivity for detecting ureteral cal-
acute urinary obstruction and urine culi and smaller calculi (<5 mm) is poor.
retention. • If no stone is found but symptoms persist,
• Nephrocalcinosis: abdominal CT-scan is indicated.
– Nephrocalcinosis is mostly asymptomatic, • Abdominal CT-scan is the most sensitive test
especially during infancy and early for identifying stones in the urinary system. It
childhood. is safe, rapid, and has been shown to have
– Sometimes, nephrocalcinosis is discovered 97 % sensitivity and 96 % specificity.
incidentally on an imaging study per- • Many radiopaque stones can be identified with
formed for other reasons. a simple abdominal radiogram (Figs. 9.1 and
– Nephrocalcinosis may also be discovered 9.2).
when symptoms of reduced concentrating • Calculi composed of uric acid, cystine, xan-
capacity of the renal tubules are obvious. thine, or indinavir are usually radiolucent.
– It is not unusual for nephrocalcinosis to be • The typical stone location is within the renal
diagnosed during systematic renal ultra- pelvis and/or the renal calyces or the ureter
sound examination of high-risk infants or and less often within the bladder.
as part of the diagnostic evaluation of uri- • The most common ureteral calcification is a
nary tract infection. stone that has migrated down from the kidney.
– The first clinical symptoms, if any of neph- These stones typically become impacted at
rocalcinosis, are gross or microscopic anatomic sites of narrowing and are especially
hematuria and/or sterile leukocyturia that difficult to detect when they overlie bony
may be misdiagnosed as urinary tract structures such as the sacrum.
infection. • Detection of a ureteral stone via ultrasonogra-
phy is difficult, but the stone may lead to
obstruction (hydroureter or hydronephrosis)
9.5 Investigations and may, thus, be suspected, even if not
directly visualized.
• Complete blood count (CBC) • Non-contrast-enhanced CT is more effective
• Electrolyte, blood urea nitrogen (BUN), than intravenous urography (IVU) in identify-
creatinine ing and locating ureteral stones.
• Serum calcium, phosphorus, alkaline phos- • Intravenous pyelography is rarely used in chil-
phatase, uric acid, total protein, albumin, para- dren (Fig. 9.3).
thyroid hormone (PTH), and vitamin D • An intravenous urography can be considered
metabolite levels in children with hypercalciuria in whom med-
• Urinalysis and culture ullary sponge kidney is suspected.
Figs. 9.1 and 9.2 Abdominal x-rays showing radio-opaque stones in two children. Note the staghorn stone in the
second x-ray
• The content of the stone (i.e., cysteine versus

calcium versus uric acid) may be the most
important element in developing a treatment
program to prevent further stone formation.
• Specific Metabolic Investigations:
– Urolithiasis developing during childhood
carry a life-long risk of stone formation.
– Approximately 16–20 % of children
develop recurrences within 3–13 years of
the first attack.
– Children with an identifiable metabolic abnor-
mality have an up to fivefold increased risk of
having a recurrence as compared with chil-
dren with no identifiable metabolic disorder.
– All children should undergo a comprehen-
sive initial evaluation.
– An infrared spectroscopy or radiograph
diffraction analysis of a passed stone is
important.
– If a cystine or struvite stone is found, the
Fig. 9.3 An intravenous urography showing a large left analysis will be diagnostic.
staghorn calculus
– Serum and urine studies should be obtained – To expedite passage or removal of any
in patients in whom stone analysis could stones present.
not be performed or for those with either – To treat associated urinary tract infection.
calcium or uric acid-based stones. – To diagnose those with predisposing condi-
– A serum creatinine level is essential to tions for urolithiasis.
evaluate for possible acute kidney injury or – To prevent new stones from forming.
chronic kidney disease. • A child presenting with acute renal colic can
– Serum calcium, phosphorous, bicarbonate, be managed with analgesics.
magnesium, and uric acid levels are effec- • This can be accomplished using simple non-
tive in screening for hypercalcemia- and steroidal analgesics.
hypocalcemia-associated calculi, hyperuri- • Narcotics may be required in those with severe
cemia, HHRH, Bartter syndrome, dRTA, pain, as well as enteral or parenteral
and FHHNC. hydration.
– Primary hyperparathyroidism is rare in chil- • In the absence of oligoanuric renal failure or a
dren and measurement of parathyroid hor- complete urinary obstruction, an intravenous
mone level is indicated if there is evidence infusion rate of 1.5–2 times their maintenance
of hypercalcemia and hypophosphatemia. is recommended.
– A 25-hydroxyvitamin D level should be • A small stone stuck at the ureteropelvic or
evaluated in all patients with hypercalcemia. ureterovesical junction may pass spontane-
– A spot urine beta-2 microglobulin (low- ously and these patients should be treated ini-
molecular-weight protein) is a useful tially conservatively.
screening test for Dent disease. • A stone that completely obstructs the bladder
– A 24-h urine collection should be analyzed outlet should be treated with catheterization
for calcium, oxalate, uric acid, sodium, using a Foley’s catheter to relive the
citrate, creatinine levels, volume, pH, and obstruction.
cystine. – The obstructing stone can then be removed
– Measuring the ratio of calcium, uric acid, from the urinary bladder.
citrate, and oxalate levels to creatinine – There are several methods to remove the
level in a random urine sample. stone:
• Vesicostomy and stone removal
• Cystoscopy, stone crushing and removal
9.6 Complications of Urolithiasis • Lithotripsy
• Children with asymptomatic stones detected
• The primary complications of urolithiasis while screening for another problem should
include: have blood and urine testing performed to
– Obstruction of the urinary tract identify underlying metabolic abnormalities.
– Renal parenchymal damage • The specific aims of surgical treatment of uro-
– Recurrent urinary tract infection lithiasis include:
– Drainage and removal of the obstruction of
the urinary tract
9.7 Management – Removal of stones present in the urinary
tract
• The management of children with urolithiasis – Surgical correction of anatomic abnormali-
include: ties, which may promote additional stone
– To diagnose children with asymptomatic formation.
urolithiasis and treat those with symptom- • A child with an infected stone and urinary
atic urolithiasis. tract infection should be treated with antibiot-
– To prevent renal damage, which may lead ics and drainage of the urinary tract in the
to loss of renal parenchyma. presence of obstruction.
9.7 Management 283
• Stones removal technique used usually • Calcium restriction is not recommended, in

depends on the stone size and location and part, because of the long-term risk of
these include: osteoporosis.
– Ureteroscopic stone extraction • Excess consumption of vitamin D with or
– Percutaneous nephrolithotomy without calcium supplements can also induce
– Open stone extraction excessive urinary calcium excretion.
– Extracorporeal shockwave lithotripsy • Excessive dietary animal protein intake causes
(ESWL). increased urinary calcium excretion and
• Alpha-1 adrenergic blocker agents, such as reduced urinary pH and citrate excretion.
doxazosin, have been used as medical expul- • Children with idiopathic hypercalciuria
sive treatment in children with distal uretral caused by renal tubular calcium leak may ben-
stones. efit from treatment with a thiazide.
• Dietary considerations depend on the type of • In those with idiopathic gastrointestinal
stone. absorptive hypercalciuria and not responding
• A high fluid intake leading to increased urine to a low-calcium diet, neutral sodium phos-
output is safe and generally beneficial for chil- phate may be beneficial in reducing dietary
dren with all types of stones. calcium absorption.
• A dietitian is important in those with dietary • Hypocitraturia is treated with oral potassium
induced urolithiasis. Children with stones citrate. Supplemental citrate leads to correc-
composed of calcium and who have excessive tion of hypocitraturia.
calcium intake or idiopathic gastrointestinal • Struvite stones require treatment with an
absorptive hypercalciuria may benefit from appropriate antibiotic.
lowered dietary calcium intake. – Surgical intervention or ESWL may be
• The goal is to lower urinary calcium such that necessary if the stone produces high-grade
no new stones are formed without producing obstruction, if antibiotic therapy is not ade-
calcium deficiency. quately eliminating infection, or after
• Fluids that increase urinary pH and citrate excre- infection is cleared to remove stone
tion such as orange juice, lemonade, and black fragments.
currant juice, as well as those that increase uri- • Uric acid stones require alkalinization of urine
nary volume such as coffee, tea, beer, and wine, with sodium bicarbonate or potassium citrate
reduce the risk of calcium stone formation. in four divided doses.
• Grapefruit juices seem to increase the risk of – Urine pH levels should be maintained at
calcium-based stones. 7.5 or greater.
• Increased sodium intake is known to promote – Uric acid is much more soluble in alkaline
calciuria by competing for reabsorption at the than acid urine.
level of the renal tubules. – Allopurinol is indicated in children with
• A low salt diet corresponding to less than uric acid stones whose daily uric acid
2–3 mEq/kg/day in children or less than 2.4 g/ excretion exceeds the reference range.
day in adolescents or adults is generally rec- – The consumption of excessive amounts of
ommended for patients with hypercalciuria or dietary animal protein also results in
calcium-containing stones. increased purine intake, increased uric acid
• A low salt diet may also reduce urinary cys- production, and may contribute to both uri-
tine excretion in patients with cystinuria. cosuria and more acidic urine.
• A higher calcium containing diet is associated – The treatment of children with uric acid
with a reduced risk of stone formation. calculi includes:
• Higher calcium intake effectively binds • A high urine flow rate
dietary oxalate in the gut, thereby reducing • Alkalization of the urine
intestinal absorption and eventual urinary oxa- • Allopurinol (4–10 mg/kg/day, adult
late excretion. maximum 300 mg/day) is indicated in
those with hyperuricemia and hyperuri- • Higher dietary magnesium has been associ-
cosuria, such as PRPSS or HPRT ated with a lower risk of stone formation, and
deficiency. magnesium supplement may be helpful in the
• Inhibition of xanthine dehydrogenase treatment of children with secondary
by allopurinol may lead to the accumu- hyperoxaluria.
lation and urinary excretion of • Carbohydrate ingestion has been associated
xanthine. with hypercalciuria, and sucrose ingestion has
• Rarely, a secondary xanthinuria with been found to be associated with urolithiasis.
xanthine calculi is observed in children • Phyate, a dietary factor found in many high
on long-term therapy. fiber-containing foods (cereals, legumes, veg-
• Allopurinol may also be the agent of etables, and nuts), seems to bind calcium
choice for treating hyperuricosuric cal- avidly and may inhibit the formation of cal-
cium oxalate urolithiasis if there is no cium oxalate stones.
concomitant evidence of hypercalciuria, • Medications:
hyperoxaluria, or hypocitraturia. – A thiazide diuretic is often required for
• The medical management of cystinuria con- children with hypercalciuria who do not
sists of: respond to a restricted sodium diet.
– Hyperhydration – The usual recommendation is hydro-
– Urine alkalization chlorothiazide 1–2 mg/kg/day (adult
– Sulfhydryl agents such as tiopronin 25–100 mg/day).
– Reducing animal protein intake might be – Amiloride can be added for its potassium-
helpful by increasing urinary pH sparing effect as well as for its ability to
• Patients with calcium oxalate stones who independently reduce calcium excretion.
demonstrate evidence of hyperoxaluria should – Thiazide diuretics have also been used in
have limited dietary oxalate ingestion. an attempt to reduce calcium excretion
– Foods that contain high levels of oxalate in patients with Dent disease, FHHNC,
include certain nuts (almonds, peanuts, and PH.
cashews, walnuts, and pecans), spinach, – Treatment with either potassium citrate
soy beans, tofu, rhubarb, beets, sweet pota- (2–4 mEq/kg/day) or potassium-
toes, wheat bran, okra, parsley, chives, magnesium citrate has been shown to
black raspberries, star fruit, green tea, and reduce the recurrence of calcium oxalate
chocolate. stone formation in patients with low or nor-
• Vitamin C supplements have been associated mal citrate excretion.
with increased risk of calcium oxalate stone – Sodium citrate is generally considered less
formation because oxalate is a byproduct of ideal because it is associated with increased
ascorbic acid metabolism. sodium delivery to the nephron.
• Vitamin C supplements should be discontin- – Potassium citrate is also used to alkalinize
ued in calcium oxalate stone formers with the urine in patients with Dent disease,
hyperoxaluria. FHHNC, dRTA, uric acid urolithiasis (goal
• Potassium-rich foods such as fruits and vege- of urine pH >6.5), cystinuria (goal of urine
tables usually contain large amounts of citrate, pH >7), and hyperoxaluria.
which are protective against the formation of – Thiol-containing agents (d-penicillamine
calcium oxalate stones. and α-mercaptopropionylglycine) are used
• A diet high in potassium is protective against exclusively for patients with cystinuria in
urolithiasis. whom fluid and dietary modifications as
• A potassium-restricted diet can cause well as urinary alkalization are ineffective in
increased urinary calcium excretion and overt preventing stone recurrences or dissolving
hypokalemia, leading to hypocitraturia. preexisting stones.
Further Reading 285
– The thiol group combines with cysteine to 7. Johnson EK, Lightdale JR, Nelson CP. Risk factors
for urolithiasis in gastrostomy tube fed children: a
form a more soluble cysteine-drug product
case-control study. Pediatrics. 2013;132(1):e167–74.
combination, which is be excreted. 8. Khositseth S, Gillingham KJ, Cook ME, Chavers
– Approximately 10–30 % of children with BM. Urolithiasis after kidney transplantation in pedi-
primary hyperoxaluria type I are pyridox- atric recipients: a single center report. Transplantation.
2004;78(9):1319–23.
ine sensitive. The treatment should be initi-
9. Mandeville JA, Gnessin E, Lingeman JE. Imaging
ated (2–5 mg/kg/day) and increased evaluation in the patient with renal stone disease.
gradually (8–10 mg/kg/day). Large doses Semin Nephrol. 2011;31(3):254–8.
of pyridoxine have been known to induce 10. McKay CP. Renal stone disease. Pediatr Rev. 2010;
31(5):179–88.
sensory neuropathies.
11. Milliner DS, Murphy ME. Urolithiasis in pediatric
patients. Mayo Clin Proc. 1993;68:241–8.
12. Moe OW, Pearle MS, Sakhaee K. Pharmacotherapy of
urolithiasis: evidence from clinical trails. Kidney Int.
2001;79:385–92.
Further Reading 13. Palmer JS, Donaher ER, O’riordan MA. Diagnosis of
pediatric urolithiasis: role of ultrasound and comput-
1. Avci Z, Koktener A, Uras N, et al. Nephrolithiasis erized tomography. J Urol. 2005;174:1413–6.
associated with ceftriaxone therapy: a prospective 14. Pietrow PK, Pope IV JC, Adams MC. Clinical out-
study in 51 children. Arch Dis Child. 2004;89(11): come of pediatric stone disease. J Urol. 2002;167:
1069–72. 670–3.
2. Bartosh SM. Medical management of pediatric stone 15. Sarica K. Pediatric urolithiasis: etiology, specific
disease. Urol Clin North Am. 2004;31:575–87. pathogenesis and medical treatment. Urol Res. 2006;
3. Bass NH, Emmanuel B. Nephrolithiasis in childhood. 34:96–101.
J Urol. 1966;95:749–53. 16. Stapleton FB. Clinical approach to children with uro-
4. Cameron MA, Sakhaee K, Orson WM. Nephrolithiasis lithiasis. Semin Nephrol. 1996;3:116–24.
in children. Pediatr Nephrol. 2005;20:1587–92. 17. Van’t Hoff WG. Aetiological factors in paediatric uro-
5. Cameron MA, Sakkhae K, Moe OW. Nephrolithiasis lithiasis. Nephron Clin Pract. 2004;98:c45–8.
in children. Pediatr Nephrol. 2005;20:1587–92. 18. VanDervoort K, Wiesen J, Frank R. Urolithiasis in
6. Evan A, Lingeman J, Coe FL. Randall’s plaque: pediatric patients: a single center study of incidence,
pathogenesis and role in calcium oxalate nephrolithia- clinical presentation and outcome. J Urol. 2007;
sis. Kidney Int. 2006;69:1313–8. 177(6):2300–5.
Persistent Müllerian Duct
Syndrome (PMDS) 10
10.1 Introduction • Affected males with this disorder have normal

male reproductive organs. They also have
• Persistent Müllerian duct syndrome (PMDS) internal female reproductive organs (a uterus
is a rare disorder of sexual development. and fallopian tubes).
• It was first described by Nilson in 1939. • The clinical features of PMDS depends on the
• It is also called persistent oviduct syndrome. mobility of the Müllerian derivatives (the
• It is considered by some to be a form of pseu- uterus and fallopian tubes) which leads to
dohermaphroditism due to the presence of either cryptorchidism or inguinal hernia. If the
Müllerian derivatives. uterus and fallopian tube are mobile, they may
• This syndrome is characterized by the persis- descend into the inguinal canal during testicu-
tence of Mullerian duct derivatives (i.e. uterus, lar descent. However, if the Müllerian deriva-
cervix, fallopian tubes and upper two thirds of tives are relatively immobile testicular descent
vagina) in a phenotypically (normal male may be impeded and the patient presents with
reproductive organs and normal male external undescended testes either unilateral or
genitalia) and karyotypically (46, XY) male bilateral.
patient.
• Persistent Müllerian duct syndrome is usually
caused by deficiency of fetal anti-Müllerian 10.2 Embryology of Persistent
hormone (AMH) effect due to mutations of Müllerian Duct Syndrome
the gene for AMH or the anti-Müllerian hor-
mone receptor, but may also be as a result of • The normal sexual differentiation depends on
insensitivity to AMH of the target organ. the genetic sex (XX or XY), which is estab-
• PMDS is caused by mutations in the AMH lished at the time of conception.
gene (PMDS type 1) or AMHR2 gene (PMDS • Following conception, the fetus is sexually
type 2) and is inherited in an autosomal reces- indifferent with two different bipotential
sive manner. gonads and two pairs of internally developing
• It affects males who have normal chromo- Wolffian and Müllerian ducts.
somes (46, XY) and have normal male repro- • These two undifferentiated bipotential gonads
ductive organs and normal male external develop from the urogenital ridge and ulti-
genitalia. mately develop into either a testis or an ovary.
• Persistent Müllerian duct syndrome affects • In addition to these bipotential gonads, fetuses
only males and is inherited in an autosomal of both sexes have also two sets of internal
recessive pattern. ducts: the Müllerian ducts and the Wolffian

288 10 Persistent Müllerian Duct Syndrome (PMDS)
ducts which develop by 6–7 weeks of intra- the genital folds, urethral folds and a urogenital
uterine life. opening. These subsequently differentiate into
• Expression of sex-determining genes on the male or female external genitalia under the
early bipotential gonad promotes develop- influence of estrogen or dihydrotestosterone.
ment of the gonad into either a testis or an • Male Differentiation:
ovary. – The male sexual differentiation depends on
• Various genes expressed by the Y chromo- two important steps:
some at very specific times during develop- • The development of the bipotential
ment are responsible for the differentiation of gonad into a testis.
the testes. • Internal and external genitalia
• In a male fetus, the testis differentiates by the differentiation.
end of the seventh gestational week. – The development of the bipotetial gonad
• A 35-kilobase (kb) gene determinant located into a testis occurs at about the sixth week
on the distal short arm of the Y chromosome, of gestation under the influence of the SRY
known as the SRY (sex determining region of gene.
the Y chromosome) is responsible for initiat- • The SRY gene is located on the short
ing the indifferent gonads to develop into arm of the Y-chromosome (Yp11.3). It
testes. is responsible for initiating sex differen-
• SRY codes for a transcription factor that acts in tiation by downstream regulation of sex-
the somatic cells of the genital ridge. determining factors.
• Expression of this gene triggers a cascade • This involves expression of several
of events that ultimately leads to the devel- genes including WT1, CBX2 (M33),
opment of testicular Sertoli and Leydig SF1, GATA4/FOG2 is critical to SRY
cells. activation.
• SRY expression directs testicular morphogen- • The SOX9 gene, located on 7q24.3-
esis, leading also to the production of MIS 25.1, is essential for early testis
(Müllerian-inhibiting substance), and, later, development.
testosterone. – The second step in male sex differentiation
• Normal sex differentiation is controlled by: involves internal and external genitalia
– Testosterone differentiation.
– Dihydrotestosterone – The developed testes have two types of
– Müllerian Inhibiting Factor (MIF). cells:
– Sertoli cells secrete MIF, which leads to • The Leydig cells
regression of the Müllerian ducts. • The Sertoli cells
– Leydig cells secret testosterone which has a – The Sertoli cells produce the anti-Müllerian
direct effect on the Wolffian ducts, and pro- hormone (AMH).
motes their differentiation into the epididy- – The Leydig cells produce testosterone.
mis, vas deferens, and seminal vesicles. – The AMH acts on its receptor in the
– Testosterone and under the influence of Müllerian ducts and causes their
5-alpha reductase is converted to regression.
Dihydrotestosterone which induces male – Testosterone acts in a critical concentration-
differentiation of external genitalia. dependent and time-dependent manner to
– Patients with PMDS have both Wolffian induce male sexual differentiation.
and Müllerian duct structures due to a defi- – Testosterone acts on the androgen receptor
ciency of MIF. in the Wolffian ducts to induce the forma-
• The external genitalia at 6–7 weeks gestation tion of:
appear female and include a genital tubercle, • Epididymis
10.2 Embryology of Persistent Müllerian Duct Syndrome 289
• Ejaculatory ducts • Female Differentiation:

• Seminal vesicles. – In females and as a result of the absence of
– The Leydig cells also produce insulin-like SRY gene, the bipotential gonad develops
factor 3 (INSL3, relaxin-like factor), which into an ovary.
play a role in the descent of testes to the – DAX1 gene is necessary for both testicular
scrotum. and ovarian development.
– Testesterone is also converted to dihy- – WNT4-signaling pathway plays a major role
drotestosterone (DHT) under the influence in ovarian development, Müllerian ducts
of 5-alpha reductase enzyme, which acts development and ovarian steroidogenesis.
on the androgen receptor of the prostate – The second step in female sex differentia-
and external genitalia to cause its tion involves internal and external genitalia
masculinization. differentiation.
– Binding of Testosterone and DHT to andro- – Absence of the anti-Müllerian hormone
gen receptors is necessary for androgen (AMH) which is secreted by the testes leads
effect. to development of the Müllerian ducts.
The SRY gene (located on the short arm of the Y-

chromosome (Yp11.3))
Bipotential gonad (Indifferent gonad)
Testis
Sertoli cells Leydig cells
Anti-Mullerian Testosterone
hormone
Wollfian ducts
Mullerian ducts
Dihdrotestosterone Epididymis
Regression Ejaculatory ducts
Seminal vesicles
Prostate and external
Masculinization
– The Müllerian ducts give rise to: – Estrogen secreted by the developing ovary
• The fallopian tubes leads to the development of the external
• Uterus genitalia of the female.
• The upper two-third of the – In the female, the genital tubercle becomes
vagina the clitoris, the labio-scrotal folds become
– Absence of testesterone leads to regression the labia majora, and the urethral folds
of the Wollfian ducts. become the labia minora.
Absence of the SRY gene (located on the short arm of the Y-

chromosome (Yp11.3)
Ovary
No Sertoli cells Estrogen
No Anti-Mullerian hormone External

Genitalia
Feminization
Mullerian ducts
The fallopian tubes, Uterus, The upper two-third of the

vagina
10.3 Etiology and Inheritance week of gestation, and Müllerian regression is

of PMDS completed by the end of the ninth week.
• The AMH induced regression of the Müllerian duct
• This condition is usually caused by deficiency occurs in cranio-caudal direction via apoptosis.
of fetal anti-Müllerian hormone (AMH) effect • The AMH receptors are on the Müllerian duct
due to mutations of the gene for AMH or the mesenchyme and transfer the apoptotic signal
anti-Müllerian hormone receptor, but may to the Müllerian epithelial cell, presumably
also be as a result of insensitivity to AMH of via paracrine actors.
the target organ. • The Wolffian ducts differentiate into epididy-
• AMH (Anti Müllerian Hormone) is produced mis, vasa differentia and seminal vesicles
by the primitive Sertoli cells as one of the ear- under the influence of testosterone, produced
liest Sertoli cell products and induces regres- by the fetal Leydig cells.
sion of the Müllerian ducts. • Most people with persistent Müllerian duct
• Fetal Müllerian ducts are only sensitive to syndrome have mutations in the AMH gene or
AMH action around the seventh or eighth the AMHR2 gene.
• The AMH gene provides instructions for mak- • It is characterized by unilateral cryptor-
ing a protein called anti-Müllerian hormone chidism with contralateral inguinal her-
(AMH). nia, and can be one of two types:
• The AMHR2 gene provides instructions for – The first type is hernia uteri inguina-
making a protein called AMH receptor type II. lis, which is characterized by one
• The AMH protein and AMH receptor type II descended testis and herniation of
protein are involved in male sex differentiation. the ipsilateral corner of uterus and
• During development of a male fetus, these two fallopian tube into the inguinal canal.
proteins work together to induce breakdown – The second type is crossed testicular
(regression) of the Müllerian duct. ectopia, which is characterized by
• Mutations in the AMH and AMHR2 genes lead herniation of both testes and the
to nonfunctional proteins that cannot signal entire uterus with both fallopian
for regression of the Müllerian duct. tubes on the same side.
• As a result of these mutations, the Müllerian – The female form:
duct persists and goes on to form a uterus and • This is seen in 10–20 % of cases.
fallopian tubes. • It is characterized by bilateral
• Approximately 45 % of cases of persistent cryptorchidism.
Müllerian duct syndrome are caused by muta- • The gonads are usually within the pel-
tions in the AMH gene and are called persis- vis, with the testes fixed within the
tent Müllerian duct syndrome type 1. round ligament in the ovarian position
• Approximately 40 % of cases are caused by with respect to the uterus.
mutations in the AMHR2 gene and are called
persistent Müllerian duct syndrome type 2.
• In the remaining 15 % of cases, no mutations 10.5 Clinical Features
in the AMH and AMHR2 genes have been
identified, and the genes involved in causing • Patients with persistent Müllerian duct syn-
the condition are unknown. drome usually present with undescended tes-
• This condition is inherited in an autosomal tes (cryptorchidism) which can be unilateral
recessive pattern. However, persistent or bilateral.
Müllerian duct syndrome affects only males. • More often, one testis has descended into the
Females with two mutated copies of the gene scrotum normally, and the other one has not.
do not show signs and symptoms of the In these cases, the uterus and fallopian tubes
condition. are in the pelvis.
• PMDS type I results from mutations of the • In cases of unilateral or bilateral cryptorchi-
gene (AMH) for AMH on chromosome 19p3.3. dism associated with hernia, the possibility of
• PMDS type II results from mutations of the gene PMDS should be kept in mind (Fig. 10.1).
(AMH-RII) for the AMH receptor on 12q13. • Sometimes they present with inguinal hernias
(Fig. 10.2).
• Sometimes, the descended testis pulls the fal-
10.4 Classification of PMDS lopian tube and uterus into the track through
which it has descended and into the inguinal
• Classically, patients with PMDS present with hernia sac. This condition is called hernia uteri
unilateral or bilateral cryptorchidism and they inguinalis, a form of inguinal hernia in which
have normal male genotypes and phenotypes. the hernia sac contains the uterus and Fallopian
• Two anatomic variants of PMDS have been tubes.
described: male and female. • In some cases with persistent Müllerian duct
– The male form: syndrome, they present with bilateral unde-
• This is the most common form encoun- scended testes and the undescended testis
tered in 80–90 % of cases. from one side is also pulled into the other side,
TESTIS
UTERUS TESTIS
FALLOPIAN
TUBES
FALLOPIAN
TUBES
Fig. 10.3 A clinical intraoperative photograph of a

patient with persistent Müllerian duct syndrome. Note the
presence of a uterus, two fallopian tubes and two testes
but no ovaries. This results from deficiency of MIS. Note
Fig. 10.1 A clinical photograph of a patient with normal also the testes fixed within the round ligament in the ovar-
looking external genitalia and undescended right testis ian position with respect to the uterus
who was found to have deficiency of MIS
patients may be primary from the testes or

secondary to obstruction or nonpatency of the
vas deferens.
• Since the patients are phenotypically male, the
diagnosis is usually not suspected and the
diagnosis is delayed or made at the time of
surgery for cryptorchidism or hernia.
• The risk of malignancy in an ectopic testis in a
case of PMDS is similar to that in a cryptor-
chid testis in a healthy male. Germ cell tumors
have been reported in the testis, whereas
tumors of the Mullerian duct derivatives are
very rare.
Fig. 10.2 A clinical photograph of a patient with normal

looking external genitalia and a large right inguinal hernia 10.6 Treatment
who was found to have deficiency of MIS
• The aim of surgical treatment is to mobilize,
forming an inguinal hernia with both unde- preserve and fix the testes in the scrotum with-
scended testes on the same side. This condi- out injuring the vessels and vas.
tion is called transverse testicular ectopia. • The associated hernia should also be
• The uterus and fallopian tubes are typically treated.
discovered intraoperatively when surgery is • During surgery, the uterus is usually removed
performed to treat undescended testes or and attempts are made to dissect away
inguinal hernia (Fig. 10.3). Müllerian tissue from the vas deferens and
• Sometimes the uterus and fallopian tubes are epididymis without injuring them to improve
discovered preoperatively via ultrasound or the chance of fertility.
MRI while investigating impalpable unde- • A vas deferens is presents bilaterally, usually
scended testes or for other reasons. running close to the uterus.
• Some of these cases may remain undiagnosed • To avoid damage to the vas, care must be taken
to present late with infertility or blood in the at the time of Müllerian remnants excision.
semen (hematospermia). Infertility in these • Rarely, the vas deferens ends blindly.
Further Reading 293
• With the recent advances of minimal invasive in patients with PMDS, whereas tumors of the
surgery, laparoscopic hysterectomy is an alter- Mullerian duct derivatives are very rare.
native technique to improve the chances of • Infertility is common in these patients, with an
fertility in these patients. absence of spermatozoa or results secondary
• The surgical management of PMDS includes: to obstruction or nonpatency of the vas
– Orchidopexy: deferens.
• Every attempt should be made to pre-
serve the testes, vas and vessels.
• This may necessitates division of the Further Reading
uterus to lengthen the vas.
• A transverse testicular ectopia may be 1. Asthana S, Deo SV, Shukla NK, Raina V, Kumar
L. Persistent Mullerian duct syndrome presenting
associated with this condition. In this, with bilateral intra-abdominal gonadal tumors and
both testes are found on the same side obstructive uropathy. Clin Oncol. 2001;13(4):304–6.
and both testes should be mobilized and 2. Clemente A, Macchi V, Berretta M, Morra A. Female
fixed one in each scrotum. form of persistent Müllerian duct syndrome: MDCT
findings. Clin Imaging. 2008;32:314–7.
– Excision of Müllerian remnants: 3. Crankson SJ, Bin Yahib S. Persistent Mullerian duct
• This is not a simple procedure and care syndrome in a child: surgical management. Ann Saudi
should be taken to avoid injury to the Med. 2000;20:267–9.
vas. 4. El-Gohary MA. Laparoscopic management of persis-
tent Mullerian duct syndrome. Pediatr Surg Int.
• In those where removal of the Müllerian 2003;19(7):533–6.
remnants is not possible, division of the 5. Guerrier D, Tran D, Vanderwinden JM, Hideux S, Van
uterus can be done to lengthen the vas Outryve L, Legeai L, et al. The persistent Mullerian
and facilitates orchidopexy. duct syndrome: a molecular approach. J Clin
Endocrinol Metab. 1989;68:46–52.
• Removal of Müllerian remnants is unnec- 6. Gutte AA, Pendharkar PS, Sorte SZ. Transverse tes-
essary, since the remnants rarely produce ticular ectopia associated with persistent Mullerian
symptoms and there is an extremely rare duct syndrome – the role of imaging. Br J Radiol.
risk of subsequent malignancy. 2008;81:E176–8.
7. Loeff DS, Imbeaud S, Reyes HM, Meller JL,
Rosenthal IM. Surgical and genetic aspects of persis-
tent Mullerian duct syndrome. J Pediatr Surg.
10.7 Prognosis 1994;29:65–6.
8. Martin EL, Bennett AH, Cromie WJ. Persistent
Mullerian duct syndrome with transverse testicular
• The prognosis depends upon the integrity of ectopia and spermatogenesis. J Urol. 1992;147:
the testicular tissue and successful correction 1615–7.
of cryptorchidism, which is often complicated 9. Ng JWT, Koh GH. Laparoscopic orchidopexy for per-
sistent Mullerian duct syndrome. Pediatr Surg Int.
by the close anatomical relationship between
1997;12:522–5.
the vas deferens and the Mullerian derivatives 10. Renu D, Ganesh Rao B, Ranganath K, Namitha.
• The risk of malignancy in an ectopic testis in a Persistent Mullerian duct syndrome. Indian J Radiol
case of PMDS is similar to that in a healthy Imaging. 2010;20(1):72–4.
11. Shamim M. Persistent Mullerian duct syndrome with
male, with the incidence being 15 %. There
transverse testicular ectopia presenting in an irreduc-
have been case reports of embryonal carci- ible recurrent inguinal hernia. J Pak Med Assoc.
noma, seminoma, yolk sac tumor and teratoma 2007;57(8):421–3.
Neurogenic Bladder Sphincter
Dysfunction 11
11.1 Introduction • The management of children with neurogenic

bladder sphincter dysfunction is similar irre-
• Neurogenic bladder sphincter dysfunction spective of the underlying cause.
(NBSD) can develop as a result of a lesion at • The aim is:
any level in the nervous system, including: – Early diagnosis
– The cerebral cortex – Early medical treatment
– The spinal cord – To prevent the adverse effects on the bladder
– The peripheral nervous system which subsequently will lead to incontinence
• In the pediatric age group, neurogenic bladder and secondary damage to the kidneys.
sphincter dysfunction can develop as a result • The management of NBSD in children has
of congenital or acquired causes. undergone major changes over the years.
• Commonly it results from congenital neural – One of the most important advancement
tube defects including: was the introduction of clean intermittent
– Myelomeningocele catheterization (CIC).
– Lipomeningocele – The second important aspect of their man-
– Spina bifida agement was the use of anticholinergics.
– Sacral agenesis – The third important breakthrough in their
– Tethered cord management is the wide use of urodynamic
• Acquired causes include: studies to diagnose these patients, classify
– Spinal cord tumors their defect and institute early and proper
– Spinal cord trauma treatment.
– Transverse myelitis • CIC, combined with anticholinergics when
• Neurogenic bladder is a term applied to a mal- necessary has made “conservative” manage-
functioning urinary bladder due to neurologic ment of children with NBSD a successful treat-
dysfunction and the symptoms depend on the ment option, with a good outcome in term of:
site of neurological insult. – Quality of life of these children
– The effect on detrusor muscle: – Avoiding damage to the kidneys
• Detrusor underactivity • Urodynamic assessment is essential for the
• Detrusor overactivity diagnosis and prognosis of pediatric neuro-
– The effect on urinary sphincter: genic bladder.
• Sphincter underactivity • Urodynamic studies are functional studies of
• Sphincter overactivity and loss of coor- the lower urinary tract; they evaluate storage
dination with bladder function. and emptying functions of the bladder.

296 11 Neurogenic Bladder Sphincter Dysfunction
• Urodynamic studies can be simple and non- function and providing safe urinary conti-
invasive (bladder diary and flow rate) or inva- nence in more than 90 % of patients with a
sive (cystometrogram and videourodynamics). neurogenic bladder.
• A cystometrogram measures the relationship
between bladder filling and pressure.
Parameters used to characterize the bladder 11.2 Physiology and Bladder
are capacity, compliance, detrusor activity and Function
sphincter activity.
• On the other hand, invasive urodynamic stud- • The urinary bladder has two functions:
ies are indicated to evaluate and characterize – To store urine (A storage function)
the neuropathic bladder. – To expel urine (A micturition function)
• Risk factors indicative of a poor prognosis • Both of these functions are well coordinated
include: and this coordinated function is regulated by
– Reduced bladder capacity for age the central and peripheral nervous systems.
– Poor compliance • During the storage phase, the urinary bladder
– Elevated detrusor leak point pressure acts as a low-pressure reservoir, while the
(>40 cm H2O) urinary sphincter maintains high resistance to
– Features of functional bladder outlet urinary flow to keep the bladder outlet closed.
obstruction on electromyography, such as • During this phase, the pressure inside the uri-
detrusor sphincter dyssynergia. nary bladder remains low.
• The urodynamic studies allows each child to • This phase depends on:
be categorized into one of four subtypes of – The intrinsic viscoelastic properties of the
neuropathic bladder dysfunction based on bladder
sphincter and detrusor muscle activity. – Inhibition of the parasympathetic nerves
Although these categories may overlap, they – Sympathetic nerves also facilitate urine
assist in patient management. storage in the following ways:
– Type A: Sphincter overactivity combined • Sympathetic nerves inhibit the parasym-
with detrusor underactivity pathetic nerves from triggering bladder
– Type B: Sphincter overactivity combined contractions.
with detrusor overactivity • Sympathetic nerves directly cause
– Type C: Sphincter underactivity combined relaxation and expansion of the detrusor
with detrusor underactivity muscle.
– Type D: Sphincter underactivity combined • Sympathetic nerves close the bladder
with detrusor overactivity neck by constricting the internal ure-
• Despite the etiology, the principles for man- thral sphincter.
agement are similar: • During micturition, the urinary bladder con-
– To insure and maintaining an adequate tracts to expel urine while the urinary sphinc-
sized, normally compliant, urinary bladder ter relaxes and opens to allow unobstructed
– To evacuates urine completely, at a rela- urinary flow and bladder emptying.
tively low pressure • As the bladder fills, the pudendal nerve
• Early diagnosis and treatment can prevent becomes excited.
both renal damage and secondary bladder- • Stimulation of the pudendal nerve results in
wall changes, thereby improving long-term contraction of the external urethral
outcomes. sphincter.
• Medical management with CIC and anticho- • Contraction of the external sphincter, coupled
linergics is effective in preserving renal with that of the internal sphincter, maintains
11.2 Physiology and Bladder Function 297
urethral pressure higher than normal bladder • The pons part of the brainstem is responsible for
pressure. coordinating the activities of the urinary sphinc-
• The combination of both urinary sphincters is ters and the bladder so that they work in synergy.
known as the continence mechanism. • This is done through the pontine micturition
• The pressure gradients within the bladder and center (PMC).
urethra play an important functional role in • The PMC coordinates the urethral sphincter
normal micturition. relaxation and detrusor contraction to facili-
• As long as the intraurethral pressure is higher tate urination.
than that of the intravesical, patients will • Stimulation of the PMC causes the urethral
remain continent. sphincters to open while facilitating the
• If the urethral pressure is abnormally low or if detrusor muscle to contract and expel the
the intravesical pressure is abnormally high, urine.
urinary incontinence will result. • The PMC is also affected by emotions, which
• The bladder and urethra are innervated by is why some people may experience inconti-
three sets of peripheral nerves arising from the nence when they are excited or scared.
autonomic nervous system (ANS) and somatic • The ability of the brain to control the PMC is
nervous system. part of the social training that children experi-
– Autonomic nervous system ence during growth and development.
• Parasympathetic (S2, S3, S4) • Usually the brain takes over the control of the
– This is motor to detrusor muscles of pons at age 3–4 years, which is why most chil-
urinary bladder dren undergo toilet training at this age.
– This is inhibitory to internal urethral • When the bladder becomes full, the stretch
sphincter receptors of the detrusor muscle send a sig-
• Sympathetic (T10 to L2) nal to the PMC, which in turn notifies the
– This is motor to internal urethral brain that there is a sudden desire to go to
sphincter the bathroom and empty the urinary
– This is inhibitory to detrusor muscle bladder.
of urinary bladder • Under normal situations, the brain sends an
– Somatic nerve (S2, S3, S4) inhibitory signal to the pons to inhibit the
• Pudendal nerves bladder from contracting until it is socially
• Micturition is a spinal reflux facilitated and acceptable to micturate.
inhibited by higher brain center and subject to • When the PMC is deactivated, the urge to uri-
voluntary facilitation and inhibition. nate disappears, allowing the patient to delay
• The brain is the master control of the entire urination until finding a socially acceptable
urinary system and this is done through the time and place.
micturition control center which is located in • When urination is appropriate, the brain sends
the frontal lobe of the brain. excitatory signals to the PMC, allowing the
• The micturition control center send inhibi- urinary sphincters to open and the detrusor
tory signals to the detrusor muscle of the uri- muscle to contract and empty the urinary
nary bladder to prevent the bladder from bladder.
contracting and emptying until a socially • All these excitatory and inhibitory signals
acceptable time and place to urinate is pass via the spinal cord (the sacral reflex
available. center).
• The signal transmitted by the brain reach the • The information (signals) from the urinary
urinary bladder through the brainstem and the bladder travels up the spinal cord via the sacral
sacral spinal cord. cord to the PMC and then to the brain.
• The brain interprets this signal and sends a – It also inhibits parasympathetic stimulation
reply via the PMC that travels down the spinal – As a result the micturition reflex is
cord to the sacral cord and, subsequently, to inhibited
the urinary bladder.
• An intact spinal cord is critical for normal Effects of the Sympathetic System on the
micturition. Urinary Bladder
• In the event of spinal cord injury, the patient • It causes bladder relaxation
will develop detrusor sphincter dyssynergia • It stimulates the internal urinary sphinc-
with detrusor hyperreflexia (DSD-DH). The ter to remain closed
patient will have urinary frequency, urgency, • It inhibit the effect of the parasympa-
and urge incontinence but cannot empty the thetic system
bladder completely. • The end result is inhibition of micturition
• In infants, the spinal reflex center is
responsible for controlling the act of mic-
turition which happens involuntary once • The parasympathetic nervous system func-
the bladder is full. When the bladder is full, tions in a manner opposite to that of the sym-
an excitatory signal is sent to the sacral pathetic nervous system.
cord (the sacral reflex center) which auto- – The parasympathetic nerves stimulate the
matically triggers the detrusor to contract detrusor to contract.
leading to involuntary detrusor contrac- – The sympathetic influence on the internal
tions and bladder emptying. This is tempo- urethral sphincter becomes suppressed so
rary and once the higher center of voiding that the internal sphincter relaxes and opens.
control (the brain) is mature enough it will – The activity of the pudendal nerve is inhib-
control and command the bladder. ited and this causes the external urethral
Voluntary continence usually is attained by sphincter to open.
age 3–4 years. – The end result is voluntary urination.
• Another important component of the act of
micturition is the autonomic nervous system
which is divided into the sympathetic and the Effects of the Parasympathetic System on
parasympathetic nervous system. the Urinary Bladder
• Under normal conditions, the bladder and • It stimulates the detrusor muscles to
the internal urethral sphincter primarily are contract
under sympathetic nervous system control. • It stimulates the internal urinary sphinc-
When the sympathetic nervous system is ter to relax and open by suppression of
active: the sympathetic effect
– It causes the bladder to relax and increase • It inhibit the effect of the pudendal nerve
its capacity without increasing detrusor which causes relaxation of the external
resting pressure urethral sphincter
– It stimulates the internal urinary sphincter • The end result is voluntary micturition
to remain tightly closed.
11.2 Physiology and Bladder Function 299
• The somatic nervous system regulates the

Somatic Nerve (S2, S3, S4) Supply to the actions of the muscles under voluntary control.
Urinary Bladder The pudendal nerve originates from the
• Stimulation leads to contractions of the nucleus of Onuf and regulates the voluntary
skeletal muscle fibers of the external actions of the external urinary sphincter and
urinary sphincter the pelvic diaphragm.
• During micturition, this nerve is inhib- – Activation of the pudendal nerve causes
ited leading to relaxation of the external contraction of the external sphincter and
urinary sphincter which allows the pelvic floor muscles and prevent
urination micturition.
– Inhibition of the activity of the pudendal
nerve causes the external urethral
sphincter to relax and open to allow
micturition
Control of Urinary Bladder Function

• The storage function of the urinary Pontine
Micturition
bladder is enabled by: Center
– Inhibition of detrusor muscles
(sympathetic innervation)
– Contraction of the striated exter- Brain Frontal Lobe
nal urinary sphincter (somatic Micturition Control
Center
innervation)
– Contraction of smooth muscle
internal sphincter (sympathetic The spinal reflex
innervation) center
• The micturition function of the urinary

The
bladder is enabled by: parasympathetic
The sympathetic
nervous system
– Relaxation of the striated external nervous system Somatic L1, L2, L3
S2, S3, S4 nerve
sphincter (somatic innervation) supply
– Relaxation of the smooth muscle S2, S3, S4
internal sphincter and opening of
the bladder neck (sympathetic
innervation)
The urinary
– Detrusor muscle contraction (para- bladder
sympathetic innervation) The internal
The external
sphincter
sphincter
SY PA
MP Ll S2
RA
AT SY
HE MP
TI AT
C HE
L2
NE TI
S3
RV C
E NE
SU RV
PP E
L3
LY SU
S4 PP
LY
THE URINARY
BLADDER
S
S2
O
M
A
TI
S3
C
N
EXTERNAL SPHINCTER
E
R
S4
V
PUDENDAL NERVE
E
S
11.3 Pathophysiological Changes of NBSD 301
11.2.1 Micturition • A repetitious cycle of bladder filling and

emptying occurs in newborn infants. The
• Bladder function is automatic but completely bladder empties as soon as it fills because the
governed by the brain, which makes the final brain of an infant has not matured enough to
decision on whether or not to void. regulate the urinary system. Because urina-
• The normal function of urination means that tion is unregulated by the infant’s brain, pre-
an individual has the ability to stop and start dicting when the infant will urinate is
urination on command. difficult.
• In addition, the individual has the ability to • As the infant brain develops, the PMC also
delay urination until a socially acceptable matures and gradually assumes voiding
time and place. control.
• When the bladder is filled to capacity, the • When the infant enters childhood (usually at
stretch receptors within the bladder wall send age 3–4 years), this primitive voiding reflex
signal to the spinal reflex center in the sacral becomes suppressed and the brain dominates
cord. These signals indicate a need to void. bladder function, which is why toilet training
• The spinal reflex center send signals to the PMC usually is successful at age 3–4 years.
which is, in turn, modulated by inhibitory and
excitatory neurologic influences from the brain.
• When an individual cannot find a bathroom 11.3 Pathophysiological Changes
nearby, the brain bombards the PMC with a of NBSD
multitude of inhibitory signals to prevent
detrusor contractions. • Under normal conditions, the detrusor mus-
• At the same time, an individual may actively cle, bladder neck, and striated external
contract the levator muscles to keep the exter- sphincter function as a synergistic unit for
nal sphincter closed or initiate distracting adequate storage and complete evacuation of
techniques to suppress urination. urine.
• When micturition is socially acceptable, the • In patients with NBSD, the bladder function is
brain sends excitatory signals to the PMC affected. This is as a result of disordered
which in turn send signals to the sacral cord. innervation of the detrusor musculature and
• The sacral cord, in turn, sends a message back external sphincter.
to the bladder indicating that it is time to • Children with NBSD and based on intravesi-
empty the bladder. cal pressure can be categorized into two
• At this point, the pudendal nerve causes relax- groups:
ation of the levator ani so that the pelvic floor – High-risk group
muscle relaxes. – Low-risk group
• The pudendal nerve also signals the external • This classification is important to predict sec-
urinary sphincter to relax and open. ondary renal damage from a neurogenic
• The sympathetic nerves send a message to the bladder.
internal sphincter to relax and open, resulting • In healthy bladders, the change in bladder-
in a lower urethral resistance. filling pressure between empty and full is nor-
• When the urethral sphincters relax and open, mally less than 10–15 cm H2O.
the parasympathetic nerves trigger contraction • Any pathophysiologic process that causes
of the detrusor muscles. either intermittent or continuous elevation of
• When the bladder contracts, the pressure gen- intravesical pressure above 40 cm H2O places
erated by the bladder overcomes the urethral the child at risk for:
pressure, resulting in urinary flow. – Upper urinary tract dysfunction
• These coordinated series of events allow – Urinary tract infections
unimpeded, automatic emptying of the urine. – Renal failure
• As a result of increased intravesical pressure • In children with NBSD, irreversible renal

above 40 cm H2O, the following changes will damage is caused by several factors:
occur: – High intravesical pressures
– The glomerular filtration rate decreases – Vesicoureteral reflux
– The pyelocaliceal and ureteral drainage – Lower urinary tract infections
deteriorates – Acute pyelonephritis
– Obstructive hydronephrosis and/or vesico-
ureteral reflux
• Even in the absence of vesicoureteral reflux or 11.4 Etiology and Clinical
upper urinary tract dilatation, high intravesical Features
pressure can impair drainage of urine into the
bladder. • Neurogenic bladder is a malfunctioning blad-
• Intermittent elevation of intravesical pressure der secondary to neurologic disorders which
may occur from: can affect:
– Detrusor hypertonia – The brain
– Hyperreflexia – The pons
– Both – The spinal cord
• Hyperreflexia may cause intermittent eleva- – The sacral cord
tion of intravesical pressure, especially if the – The peripheral nerves
external sphincter remains tight rather than • Detrusor hyperreflexia:
relaxes in an attempt to prevent micturition – This refers to overactive bladder symptoms
(detrusor sphincter dyssynergia). due to a suprapontine upper motor neuron
• Over a long period of time, hyperreflexia with neurologic disorder.
pressures exceeding 40 cm H2O may result in: – The external sphincter functions normally.
– Detrusor decompensation (areflexia from – The detrusor muscle and the external
myogenic failure) sphincter function in synergy.
– Detrusor hypertrophy with associated saccu- – Detrusor hyperreflexia is characterized by
lations and subsequent diverticula formation. the presence of involuntary detrusor con-
– Loss of the elastic and vesicoelastic prop- tractions, usually at low volumes.
erties of the bladder – This can produce symptoms of urgency
– Mechanical ureterovesical junction and urge incontinence.
obstruction – The treatment is composed of anticholiner-
• Continuous elevation of intravesical pressure gic medications to reduce contractions and
above 40 cm H2O may occur from a hyper- timed voiding or use of CIC.
tonic detrusor or a hypertrophic small-capacity • Detrusor external sphincter dyssynergia
bladder secondary to outflow obstruction. (DSD):
• Bladder outlet obstruction is caused by: – There is increased sphincter activity during
– Detrusor sphincter dyssynergia detrusor contraction.
– Fibrosis of the external urethral sphincter sec- – DSD has been associated with an increased
ondary to partial or complete denervation. risk of upper GU tract deterioration in as
• Bladder outlet obstruction will lead to elevated many as 70 % of patients.
voiding pressures, which will contribute to – DSD is typically managed with CIC and
either detrusor decompensation or hypertrophy. anticholinergic medications.
• It is also important to note that residual urine • DSD-DH (detrusor sphincter dyssynergia
in the bladder is a cause of recurrent urinary with detrusor hyperreflexia):
tract infections and these may affect the uri- – This refers to overactive bladder symptoms
nary bladder leading to damage, inflammation due to neurologic upper motor neuron dis-
and fibrosis of the urinary bladder. order of the suprasacral spinal cord.
11.4 Etiology and Clinical Features 303
– Both the detrusor and the sphincter are – This is managed with CIC, surgical resec-
contracting at the same time; they are in tion of the obstructing lesion, or urinary
dyssynergy (lack of coordination). diversion in extreme cases.
– The patient will have urinary retention. • Urinary retention:
• Detrusor hyperreflexia with impaired contrac- – This refers to the inability of the urinary
tility (DHIC): bladder to empty.
– This refers to overactive bladder symp- – The cause may be neurologic or
toms, but the detrusor cannot generate nonneurologic.
enough pressure to allow complete bladder • The central nervous system is considered the
emptying. master control of the urinary bladder function
– The external sphincter is in synergy with and lesions affecting this will affect the entire
detrusor contraction but the detrusor is too voiding cycle.
weak to mount an adequate contraction for • Any part of the nervous system may be
proper voiding to occur. affected, including the brain, pons, spinal
– The condition is similar to urinary reten- cord, sacral cord, and peripheral nerves.
tion, but irritating voiding symptoms are • This will result in symptoms of dysfunctional
prevalent. voiding, ranging from acute urinary retention
• Detrusor instability: to an overactive bladder or to a combination of
– This refers to overactive bladder symptoms both.
without neurologic impairment. – Urinary incontinence results from a dys-
– The external sphincter functions normally, function of the bladder, the sphincter, or
in synergy. both.
• Overactive bladder: – Bladder overactivity (spastic bladder) is
– This refers to symptoms of urinary urgency, associated with the symptoms of urge
with or without urge incontinence incontinence.
– It is usually associated with frequency and – Sphincter underactivity (decreased resis-
nocturia. tance) results in symptomatic stress
– The cause may be neurologic or incontinence.
nonneurologic. – A combination of detrusor overactivity and
• Detrusor areflexia: sphincter underactivity may result in mixed
– This refers to complete inability of the symptoms.
detrusor muscle to empty the urinary • Lesions of the brain above the pons affect the
bladder due to a lower motor neuron lesion master micturition control center, causing a
(e.g. sacral cord or peripheral nerves). complete loss of voiding control.
– The bladder does not generate a – The voiding reflexes of the lower urinary
contraction. tract remain intact.
– The result is that the bladder will not empty – The clinical features include:
(stasis). • Urge incontinence
– These patients can occasionally void with • Spastic bladder (detrusor hyperreflexia
abdominal straining, but, except in rare or overactivity)
cases, they need to be managed with clean • The bladder empties too quickly and too
intermittent catheterization (CIC). often, with relatively low quantities, and
• Outflow obstruction: storing urine in the bladder is difficult.
– In patients with outflow obstruction, high • These patients usually rush to the bath-
voiding and/or storage pressures are room and even leak urine before reach-
seen. ing there.
– This is associated with increased risk of • They may wake up frequently at night to
upper urinary tract deterioration. void.
– The causes include: • Traumatic

• Stroke • Lumbar laminectomy
• Brain tumors • Radical hysterectomy
• Parkinson disease • Abdominoperineal resection
• Hydrocephalus – In children, a tethered cord is a cause of
• Cerebral palsy dysfunctional voiding symptoms.
• Shy-Drager syndrome • Peripheral neuropathy as seen in those with
• Diseases or injuries of the spinal cord between diabetes mellitus and AIDS is a cause of uri-
the pons and the sacral spinal cord also result nary retention.
in spastic bladder or overactive bladder. – This leads to silent, painless distention of
– Initially, after spinal cord trauma, there is a the bladder.
spinal shock where the nervous system – These patients will have difficulty urinating.
shuts down. After 6–12 weeks, the nervous – They also may have a hypocontractile
system reactivates. bladder.
– When the nervous system becomes reacti- – Other diseases include:
vated, it causes hyperstimulation of the uri- • Poliomyelitis
nary bladder. • Guillain-Barré syndrome,
• These patients experience urge • Severe herpes in the genitoanal area
incontinence. • Pernicious anemia
• The bladder empties too quickly and too • Tabes dorsalis
frequently. • The most common cause of neurogenic blad-
• If both the bladder and external sphinc- der dysfunction in children is neurospinal
ter become spastic at the same time, the dysraphism.
patients will sense an overwhelming • The most common presentation is at birth with
desire to urinate but only pass a small myelodysplasia.
amount of urine (detrusor-sphincter dys- • The term myelodysplasia includes a group of
synergia) because the bladder and the developmental anomalies that result from
external sphincter are not in synergy. defects in neural tube closure.
– Children born with myelomeningocele • Lesions may include:
may have spastic bladders and/or an open – Spina bifida occulta
urethra or they may have a hypocontractile – Meningocele
bladder instead of a spastic bladder. – Lipomyelomeningocele
• Sacral cord injury may prevent the bladder – Myelomeningocele
from emptying. • Other causes of neurogenic dysfunction include:
– If a sensory neurogenic bladder is present, – Sacral agenesis
the affected patient may not be able to – Tethered spinal cord associated with imper-
sense when the bladder is full. forate anus, cloacal malformations
– In the case of a motor neurogenic bladder, – Spinal cord injuries from sporting injuries
the patient will sense the bladder is full and and motor vehicle accidents
the detrusor may not contract, a condition – Central nervous system abnormalities
known as detrusor areflexia. include spastic diplegia (cerebral palsy)
– These patients have difficulty eliminating and learning disabilities, i.e. attention
urine and experience overflow inconti- deficit hyperactivity disorder (ADHD) or
nence; the bladder gradually overdistends attention deficit disorder (ADD).
until the urine spills out. • Myelomeningocele is by far the most common
– The causes of sacral diseases include: defect seen and the most detrimental.
• Sacral cord tumors • Myelomeningoceles account for 90 % of open
• Herniated disc spinal dysraphism.
• The overwhelming majority of myelomenin- cord ‘rises up’ the canal with elongation of
goceles are directed posteriorly, with most the fetus, contribute to a variable picture of
defects involving the lumbar vertebrae. neural injury to the lower urinary tract and
• A small number (approximately 5 %) of lower extremities.
patients with myelomeningoceles do not have – This is coupled with obstruction of the
a neurogenic bladder. aqueduct to the fourth ventricle (Chiari
• Congenital defects of spinal column forma- malformation).
tion that are not open defects are often termed – The main issue is whether or not the child
spina bifida occulta. has detrusor external urethral sphincter
• The lesions can be subtle, often with no obvi- dyssynergy and whether the infant can
ous signs of motor or sensory denervation; empty the bladder completely at low
however, in many patients, a cutaneous abnor- pressure.
mality can be seen overlying the lower spine. – It is important to investigate these patient
This can vary from a dimple or a skin tag to a early including:
tuft of hair, a dermal vascular malformation, • A renal and bladder ultrasound
or an obvious subdermal lipoma. • A catheterized measurement of urine
• The frequency of abnormal lower urinary tract residual after voiding or leaking
function in patients with spina bifida occulta • Serum creatinine
has been reported to be as high as 40 %. • A urodynamic study that incorporates
• Traumatic and neoplastic spinal lesions of the both detrusor pressure measurements and
cord are less frequent in children. urethral sphincter electromyography.
• Additionally, different growth rates between • Voiding cystography is done when
the vertebral bodies and the elongating spinal there is hydronephrosis and/or urody-
cord can introduce a dynamic factor to the namic studies indicate bladder outlet
lesion. Scar tissue surrounding the cord at the obstruction with either increased pres-
site of meningocele closure can also tether the sure at capacity or bladder sphincter
cord during growth. dyssynergy.
• Sacral agenesis, defined as the absence of two • The incidence of reflux when there is
or more lower vertebral bodies, is another functional obstruction of the bladder
defect that can produce voiding dysfunction outlet can range as high as 50 %.
• Total or partial sacral agenesis is a rare con- – The presence of the following factors
genital anomaly that involves absence of part which can result in upper urinary tract
or all of one or more sacral vertebrae. deterioration calls for early treatment with
• This anomaly can be part of the caudal regression clean intermittent catheterization (CIC)
syndrome and has to be considered in any child and anticholinergic drugs:
presenting with anorectal malformation (ARM). • Elevated detrusor filling pressure
• Cerebral palsy patients may also present with • Bladder sphincter dyssynergy
varying degrees of voiding dysfunction usu- • High voiding or leaking pressures
ally in the form of uninhibited bladder con- (above 40 cm H2O) at capacity
tractions, voiding dysfunction often due to • Reflux grade III or higher
spasticity of the pelvic floor and sphincter – Most clinicians now advocate full investi-
complex and wetting. gation of the lower urinary tract and initiate
• Bladder sphincter dysfunction is poorly cor- prophylactic treatment if there are signs of
related with the type and spinal level of the outlet obstruction and/or elevated bladder
neurological lesion. filling or voiding pressure.
• Myelomeningocele – This is to avoid urinary tract deterioration
– The exposed spinal cord and its nerve which can be greater than 50 % if a watch
roots, and tension on the spinal cord as the and wait policy is adopted.
– There are several advantages of starting complications including mucus produc-

CIC and anticholinergic therapy in infancy. tion, recurrent urinary infection, elec-
• The parents and the child adapt to the trolyte imbalance, stone formation and
routine of CIC much easier than they rarely the late occurrence of cancer in
would have if it were to be begun when the augmented segment.
the child is older • Surgeries to increase bladder outlet
• The bladder often remains very compli- resistance include implantation of an
ant, expanding as the child grows artificial urinary sphincter, bladder neck
• The bladder maintain appropriate wall tightening, using adjacent tissue, a fas-
thickness cial sling, and various bulking agents.
• Hydronephrosis and vesicoureteral • Creating a catheterizable urinary stoma
reflux develop in fewer than 10 % in those children with intractable ure-
• Continence is readily achieved in greater thral incontinence or inability to cathe-
than 50 % with no additional maneuvers terize their urethra easily.
• The need for augmentation cystoplasty • Occult spinal dysraphism:
is markedly reduced from almost – The wide spread use of spinal ultrasound
60–16 % when compared with that in and MRI increased the detection and diag-
children followed expectantly. nosis of occult spinal dysraphism.
• Reduced effect on renal function and – Occult spinal dysraphism is known to be
renal scarring associated with:
– When vesicoureteral reflux is present, CIC • An intraspinal lipoma or
effectively lowers the intravesical empty- lipomeningocele
ing pressure. • A diastematomyelia
– Anticholinergics can be added to lower • A fatty filum with tethering
detrusor filling pressure, increasing com- • A dermal sinus tract
pliance without fear of causing urinary • A cutaneous lower midline back lesion
retention when combined with CIC. is detected in 90 % of patients with
– The lowered filling and emptying pressures occult spinal dysraphism
has proven to be very beneficial. – A subcutaneous mass
– In 30–50 % of children reflux is resolved – A dermal vascular malformation
within 2–3 years of its discovery and initia- – Hypertrichosis
tion of therapy. – A midline dimple or sinus tract
– The disadvantages include a higher rate of – A skin tag
bacteriuria (60–70 % versus 30 % in those – An asymmetric gluteal cleft
treated expectantly) but a lower rate of – Most infants have no other manifesta-
symptomatic urinary tract infection (20 % tion of this disease (other than the cuta-
versus 40 % in those treated expectantly). neous lesion) but the neurologic lesion
– Credé voiding is to be avoided. progress with advancing age.
– Several alpha sympathomimetic agents, – Normally, the conus medullaris ends at
such as phenylpropanolamine, ephedrine or L1, L2 at birth but ‘rises’ cephalad to
pseudoephedrine, are used to increase blad- T12, L1 at puberty.
der outlet resistance when it is not sufficient – The differential growth rate between the
to maintain continence between CICs. spinal cord and the vertebral bodies
– A variety of surgical procedures can be stretches the lower cord and cauda
used in selected patients to lower intravesi- equina due to fixation of the filum termi-
cal pressure and increase bladder capacity nale to the bottom of the vertebral canal,
and or increase bladder outlet resistance. or the nerves roots emerging from the
• Bladder augmentation is the commonest cord become compressed by an expand-
procedure but this is not without ing intraspinal lipoma.
– With time, this stretching and/or com- • In familial cases of sacral agenesis asso-
pression affects the oxidative process of ciated with the Currarino triad syndrome
the neural tissue that then leads to (presacral mass, sacral agenesis and
impaired function of the lower extremi- anorectal malformation).
ties and/or lower urinary tract. • Sacral agenesis may represent one point
– These patients should be investigated on a spectrum of abnormalities that
including a renal and bladder ultrasound encompass a sacral meningocele and
and a urodynamics study. ano-rectal malformations.
– The findings of urodynamics studies in – In the newborn period these infants appear
children less than 1 year old are invari- normal and the pathognomic sign is
ably normal. absence of the upper end of the gluteal
– The most common findings in infancy cleft, with flattened buttocks.
are partial denervation of the urethral – When the diagnosis is considered a lateral
sphincter muscle or failure of the spine film or a spinal ultrasound in infants
sphincter to relax during a detrusor will confirm the abnormality.
contraction. – A spinal MR reveals a sharp cut off to the
– The most common findings in older cord at about T-12, with nerve roots stream-
children are extensive denervation of ing from it.
the sphincter and/or an acontractile – Approximately 90 % of children develop
detrusor combined with changes in neurogenic bladder dysfunction.
lower extremity function. – These patients may have:
– A voiding cystourethrogram is indicated • An overactive detrusor with sphincter
when the urodynamics parameters sug- dyssynergy leading to recurrent urinary
gest risk to the upper urinary tract from tract infection and vesicoureteral reflux
increased bladder outlet resistance or • Or an acontractile detrusor with com-
poor detrusor compliance. plete denervation in the urethral sphinc-
– Vesicoureteral reflux, hydronephrosis ter leading to continuous incontinence.
and urinary incontinence are all man- – The management depends on the type of
aged similar to those with neurogenic dysfunction.
myelomeningocele. • CIC, anticholinergics and antibiotics are
– The abnormal neurological effects can indicated in those with an upper motor
improve following spinal cord de-teth- neuron type lesion
ering when performed in infant, but this • Surgical interventions with CIC are
is unlikely when performed in older indicated in those with an incompetent
children. sphincter mechanism.
• Sacral agenesis: • Cerebral palsy:
– This is defined as partial or complete – This results from a non-progressive injury
absence of the lowermost vertebral bodies. to the brain, occurring in the perinatal
– Sacral agenesis can range from absence of period, commonly following a period of
just the last two or three sacral bodies to the brain hypoxia or infection.
absence of sacral and several lumbar bones – The incidence of cerebral palsy is increas-
as well (sirenomyelia) (Figs. 11.1, 11.2, ing, as more severely premature infants are
and 11.3). surviving.
– This can be seen: – Cerebral palsy produces a neuromuscular
• In offspring of insulin-dependent dia- disability or complex of cerebral dysfunc-
betic mothers (1 %) tion symptoms.
• As part of a genetic disorder due to a – It is commonly seen:
deletion of part of chromosome 7 (7q36) • In prematures who are less than 2 kg at
(HLXB9 genetic mutations). birth
Figs. 11.1, 11.2, and 11.3 Clinical and radiological pictures of a patient with caudal regression syndrome
• In newborns following intraventricular – Most children with cerebral palsy develop

hemorrhage total urinary control.
• In newborns who experienced a neona- – Incontinence is seen in approximately 24 %
tal seizure of affected children. This may be related to
• In newborns who received mechanical the physical handicap rather than true
ventilation for a prolonged period of time incontinence.
– Children with cerebral palsy rarely develop (spinal cord injury without radiologic
urinary tract infection and vesicoureteral abnormality).
reflux and their kidneys are usually normal – In children, this injury may be a transient
on ultrasound. event and although sensation and motor
– In cerebral palsy, an upper motor neuron function of the lower extremities may be
lesion leads to bladder dysfunction with detru- restored relatively quickly, the dysfunction
sor overactivity (80 %), but not necessarily involving the bladder and rectum may per-
with detrusor sphincter dyssynergy (5 %) sist considerably longer.
– On the other hand, a lower motor neuron – During the acute phase of the injury:
lesion with sphincter denervation due to • The bladder is often acontractile and the
spinal cord involvement can be seen as well urethral sphincter nonreactive, although
(11 %). normal-appearing bioelectric potentials
– These patients have some ability to prevent can be recorded on sphincter EMG (spi-
leaking from an overactive detrusor by nal shock).
tightening the muscle for a variable period • Over a variable but unpredictable period
of time. of time, detrusor contractility and
– Children with milder forms of cerebral palsy sphincter reactivity return as spinal cord
dysfunction, with just learning disabilities edema subsides.
without spasticity, have an overactive detru- • With this return of function, an overac-
sor. This is often associated with either tive detrusor and bladder-sphincter
urgency (with or without incontinence) and dyssynergy may develop if the lateral
nocturia, or day and night wetting. reticulospinal cord pathways to and
– Anticholinergics are valuable for these from the brainstem have been
patients and it is the treatment of choice. disrupted.
These must be monitored to prevent the • When the lesion affects the cauda
development of retention. equina, there is probably little to no
• Traumatic injuries to the spine return of bladder or sphincter function.
– These are rare and more commonly seen in – Over time, the urodynamic pattern in
boys than girls and the frequency increases patients with a thoracic-level lesion is:
with age. • An overactive detrusor with sphincter
– It occurs as a result of: dyssynergy
• A motor vehicle accident • High voiding pressures
• A bicycle accident • Eventual hydronephrosis and vesicoure-
• A fall from a high place teral reflux
• A gunshot wound – Patients with an upper thoracic or cervical
• A sport accident lesion are likely to exhibit autonomic dys-
• Iatrogenically after surgery to correct reflexia with a spontaneous discharge of α1
scoliosis, kyphosis or other intraspinal stimulants during bladder filling and with
lesions, congenital aortic anomalies, or contractions of the detrusor that require
patent ductus arteriosus operations careful monitoring of their blood pressure
• A hyperextension injury during high during any investigational studies of the
forceps delivery lower urinary tract.
– The lower urinary tract dysfunction that – The early management consist of:
ensues is not likely to be an isolated event • Foley catheter insertion to drain the uri-
but is usually associated with loss of sensa- nary bladder
tion and paralysis of the lower limbs. • CIC should be begun as soon as feasible
– In children, radiologic investigation of the and this should be tapered and stopped
spine may not reveal any bony abnormality. when the residual urines become insig-
This condition has been labeled SCIWORA nificant (<5 ml)
• Urodynamics studies should be per- • Uroflow rate:

formed no earlier than 6 weeks after the – Uroflow rate is volume of urine voided per
injury, to allow stabilization of the unit of time.
extent of the neurologic injury – It is used to evaluate bladder outlet
• Renal ultrasonography should be part of obstruction.
the assessment – Low uroflow rate may reflect urethral
• Voiding cystography is done in those obstruction, a weak detrusor, or a combina-
with signs of potential risk (i.e. sphinc- tion of both.
ter dyssynergy or poor detrusor – This test alone cannot distinguish an
compliance). obstruction from a contractile detrusor.
• The aim is to achieve low detrusor fill- • Urodynamic studies are essential for the diag-
ing and voiding pressures with complete nosis and management of children with neuro-
emptying and in the absence of this, genic bladder.
these patients should continue on CIC in • It is important to determine several urody-
addition to anticholinergics. namic parameters, including:
– Bladder capacity
– Bladder compliance
11.5 Investigations and Diagnosis – Intravesical-filling pressure
– Intravesical pressure at the moment of ure-
• Urinalysis, and urine culture thral leakage
• Serum electrolytes, BUN and creatinine – Presence or absence of reflex
levels – Detrusor activity
• Abdominal ultrasonography – Competence of the internal and external
• Lateral spine radiography is important to look sphincteric mechanisms
for vertebral anomalies especially sacral – Degree of coordination of the detrusor and
agenesis. sphincteric mechanisms
• Magnetic resonance imaging – Voiding pattern
• Voiding cystourethrography (Figs. 11.4, 11.5, – Postvoiding residual urine volume
11.6, and 11.7): – Detrusor and abdominal storage
– A voiding cystourethrogram can assess – Voiding pressures
bladder neck and urethral function (inter- – Urine flow rate
nal and external sphincter) during filling – Postvoiding residual volume
and voiding phases. – The relationship between detrusor contrac-
– A voiding cystourethrogram can identify a tion and the urinary sphincter
urethral diverticulum, urethral obstruction, – If contrast is instilled in the bladder, the
and vesicoureteral reflux. anatomy can be imaged during voiding
• Ultrasonography of the spinal canal can be • A urodynamic study consists of the
useful in infants younger than 5 months; followings:
however, once the vertebrae begin to ossify, – The child is catheterized with a triple-
ultrasonography becomes much less lumen urodynamic catheter after lubricat-
sensitive. ing the urethra with 1 % liquid lidocaine.
• Measure of residual urine: – The intravesical pressure is recorded first.
– The postvoid residual urine (PVR) mea- – The bladder is drained and the residual
surement is important. urine carefully measured and the residual
– If the PVR is high, the bladder may be volume pressure is determined.
acontractile or the bladder outlet may be – This helps determine detrusor compliance
obstructed. at natural filling and is more accurate than
– Both of these conditions will cause urinary cystometric compliance measured during
retention with overflow incontinence. even slow filling of the bladder.
Figs. 11.4, 11.5, 11.6, and 11.7 Micturating cystourethrograms showing neurogenic bladder
– A small balloon catheter is passed into the – External urethral sphincter electromyogra-
rectum to measure intra-abdominal pres- phy (EMG) is performed using a 24-gauge
sure during the filling and emptying phases concentric needle electrode inserted peri-
of the study. neally in boys or para-urethrally in girls
– The side-hole port of the urethral pressure and advanced into the skeletal muscle
channel is positioned at the highest point of component of the sphincter until individual
resistance in the urethra and kept in place. motor unit action potentials are seen or
– This measures resistance throughout blad- heard on a standard EMG recorder.
der filling and emptying to determine the – The characteristics of the individual motor
leak point pressure. unit potentials at rest, in response to various
sacral reflexes (i.e. bulbocavernosus, ano- – Pressures within the bladder (intravesical)
cutaneous, Valsalva and Credé maneuvers) and the abdominal compartment are mea-
and bladder filling and emptying are sured, and by subtracting the abdominal
recorded to detect degrees of denervation. pressure from the intravesical pressure, the
– Next, the bladder is filled through the sec- pressure generated by the detrusor muscle
ond port while intravesical pressure is can be calculated.
monitored via the third port of the tri-lumen – Because the child is monitored through a
urodynamic catheter. filling and voiding phase, bladder capacity
– The rate of bladder filling is set at 10 % of can be quantified, and the urine flow rate,
expected capacity for age. postvoiding residual volume, and the force
– The expected bladder capacity in milliliters generated by a bladder contraction can be
= age (in years) +30 × 30. measured.
– Detrusor pressure measurements are con- – A filling cystometrogram assesses the
tinuously recorded throughout filling to bladder capacity, compliance, and the
calculate compliance, and during voiding presence of phasic contractions (detrusor
or leaking to denote emptying pressure. instability).
– Detrusor overactivity: – A voiding cystometrogram (pressure-flow
• This is defined as any short-lived pres- study) simultaneously records the voiding
sure rise of >15 cm H2O from baseline detrusor pressure and the rate of urinary
before capacity is reached. flow. This is the only test able to assess
– Sometimes, the urodynamics study is com- bladder contractility and the extent of a
bined with fluoroscopic video-imaging bladder outlet obstruction.
using a dilute radio-opaque contrast agent • Electromyography
to visualize the appearance of the bladder – If more information is desired, electromy-
wall and bladder neck or to detect the pres- ography (EMG) can be used to demonstrate
ence of vesicoureteral reflux during the test. the relationship between the detrusor mus-
– Alternatively, a radionuclide agent is cle and the external urinary sphincter.
instilled, with the patient lying above a – Electromyography (EMG) helps to ascer-
nuclear camera, to determine at what pres- tain the presence of coordinated or uncoor-
sure reflux occurs, when it is known to be dinated voiding. Failure of urethral
present beforehand. relaxation during bladder contraction results
– The study is not considered complete until in uncoordinated voiding (detrusor sphinc-
the child actually urinates or leaks and the ter dyssynergia). During normal voiding, the
‘voiding’ pressure is measured. sphincter relaxes as the detrusor muscle
– The small size of the urodynamic catheter contracts to allow unobstructed urinary flow.
does not seem to affect the voiding pressure – Spinal cord injury can lead to discoordina-
adversely, even in very young children. tion so that the sphincter is closed when the
– The normal end filling pressure should be detrusor contracts, creating high pressures
<10 cm H2O, while the normal voiding within the bladder but low flow rates.
pressure varies from 55 to 80 cm H2O in – This is known as detrusor-sphincter dys-
boys and from 30 to 65 cm H2O in girls. synergy (DSD).
– Urodynamic assessment can provide repro- – EMG allows accurate diagnosis of detrusor
ducible results in newborns and infants, but sphincter dyssynergia common in spinal
it requires attention to mechanical factors cord injuries
and filling rates. – In infants with DSD, increased EMG activ-
• The main urodynamic study is cystometrogra- ity occurs during voiding.
phy (CMG). – The presence of DSD places infants at a
– A small catheter is placed in the bladder, much greater risk of upper urinary tract
and the bladder is slowly filled with liquid. deterioration.
11.6 Classification of Neurogenic Bladder 313
• Fluoroscopy 11.6 Classification of Neurogenic

– Fluoroscopy can be used to perform video- Bladder
urodynamic imaging with contrast
enhancement of the bladder, which allows • There are various systems of classification of
the bladder to be depicted during voiding. neurogenic bladder.
– In addition, reflux may be identified. • Urodynamic and functional classifications
– If a closed sphincter is revealed during have been more practical for defining the
voiding, this finding strongly suggest the extent of the pathology and planning treat-
presence of DSD, often obviating the need ment in children.
for EMG studies. • The main classification of neurogenic
• Videourodynamics bladder is that based on urodynamic
– Videourodynamics is important for evalua- findings.
tion of a patient with incontinence. • The bladder and sphincter are two units work-
– Videourodynamics combines the radio- ing in harmony to make a single functional
graphic findings of voiding cystourethrogram unit.
(VCUG) and multichannel urodynamics. • The initial approach should be to evaluate the
– Videourodynamics enables documentation of state of each unit and define the pattern of
lower urinary tract anatomy, such as vesico- bladder dysfunction.
ureteral reflux and bladder diverticulum, as • This depends on the nature of the neurological
well as the functional pressure-flow relation- deficit:
ship between the bladder and the urethra. – The bladder may be overactive with
• The urodynamics examination findings are increased contractions, low capacity and
considered normal when there is: compliance or inactive with no effective
– An appropriate capacity contractions.
– A good compliant bladder – The outlet sphincter may be independently
– No overactivity overactive causing functional obstruction
– Normal innervation of the sphincter with or paralyzed with no resistance to urinary
normal sacral reflexes flow.
– An increase in sphincter activity during fill- – These conditions may present in different
ing and complete silencing during emptying. combinations.
• An upper motor neuron lesion is present when • This is important to plan a rational treatment
there is: for each individual patient.
– Detrusor overactivity • Urodynamic Studies are important to evaluate
– And/or hyperactive EMG responses to the lower urinary tract function and its devia-
sacral reflexes tions from normal.
– And/or a failure of the sphincter muscle, on • Since the treatment plan mainly depends upon
EMG, to relax (either partially or com- a good understanding of the underlying prob-
pletely) with a bladder contraction or leak- lem in the lower urinary tract, a well per-
ing at capacity. formed urodynamic study is mandatory in the
• A lower motor neuron lesion is present when evaluation of each child with neurogenic
there are: bladder.
– No contractions of the detrusor muscle • A urodynamic study is also important to
– And/or there is a degree of denervation, either assess the response of the vesicourethral unit
partial or complete, in the sphincter muscle, with to therapy.
characteristic EMG changes in the motor units • In meningomyelocoele, most patients will
or no motor unit activity at all, respectively present with hyperreflexive detrusor and dys-
– And little or no response in the sphincter to synergic sphincter, which is a dangerous com-
sacral reflexes and/or bladder filling or bination as pressure is built up and the upper
emptying. urinary tract is threatened.
CLASSIFICATION OF NEUROGENIC BLADDER
TYPE SPHINCTER DETRUSOR
A OVERACTIVE UNDERACTIVE
B OVERACTIVE OVERACTIVE
C UNDERACTIVE UDERACTIVE
D UNDERACTIVE OVERACTIVE
11.7 Management • Anticholinergic drugs are useful to treat the

neurogenic detrusor overactivity associated
• Bladder dysfunction is a general term used to with types B and D bladder dysfunction by
describe abnormalities in either the filling improving functional capacity and reducing
and/or emptying of the bladder. filling pressures.
• It is a common problem in children and con- • Types A and C bladder dysfunctions usually
stitutes up to 40 % of pediatric urology clinic require clean intermittent catheterisation
visits. alone, with marginal benefit expected from
• Early identification and treatment of children anticholinergics.
at high risk of urinary dysfunctions is impor- • The majority of children with neurogenic
tant in order to protect renal function and bladder (70–90 %) are effectively managed
avoid urinary incontinence. with oral anticholinergics and clean intermit-
• During normal bladder function, acetylcho- tent catheterization, avoiding the need for sur-
line released from parasympathetic nerves gical intervention, e.g. augmentation
activates muscarinic receptors in the bladder cystoplasty or bladder outlet surgery.
which result in detrusor contraction and • Side-effects of anticholinergic agents include:
micturition. – Dry mouth
• There are five subtypes (M1–M5) of musca- – Blurred vision
rinic receptors expressed in the bladder. Of – Constipation
these, M2 receptors are the most abundant, – Facial flushing
although M3 receptors are more functionally – Dizziness
active. • Clean intermittent catheterization is a safe and
• In patients with a neuropathic bladder, disor- effective method of completely emptying the
dered innervation commonly results in dys- bladder, improving or eliminating urinary
synergia between the detrusor and external incontinence, reducing UTIs and protecting
sphincters, which adversely affects bladder (along with anticholinergics) kidney function.
function. Clean intermittent catheterization should be
• Oral anticholinergics, such as oxybutynin, done three-hourly.
block these receptors, causing relaxation of • The Credé maneuver (manual suprapubic
the bladder’s smooth muscle, and are well pressure to expel urine) is discouraged.
established as the first line pharmacotherapeu- • Surgical options for failure of conservative
tic agents to treat neurogenic bladder. treatment include augmentation cystoplasty,
11.7 Management 315
which increases bladder capacity and reduces • Others advocate selective urodynamic studies
pressure. and depend on serial radiologic imaging to
• The goals of management are: detect secondary evidence of high bladder
– To prevent or minimize secondary damage pressure. They advocate prompt intervention
to the upper urinary tracts and bladder from at first signs of deterioration They reserve uro-
the primary neurogenic bladder dysfunction dynamic studies only for patients with evi-
– To achieve safe social continence dence of urinary retention on physical
• The optimal management of neurogenic blad- examination, new-onset hydronephrosis or
der involves: febrile urinary tract infection, or for evalua-
– Early diagnosis tion to achieve continence.
– Identifying high-risk groups • Urodynamic assessment is important to clas-
– Institution of adequate treatment sify NBSD.
– Creating a low-pressure bladder reservoir • This allows presymptomatic interventions in
– Ensuring complete and safe bladder the high-risk groups and plan treatment
emptying according to the type of dysfunction.
• Early proactive treatment of high-pressure • The management must start before consequences
dyssynergic lower urinary tracts is important of bladder dysfunction become apparent.
in the long term, not only to preserve renal • Clean intermittent catheterization (CIC) or
function but also to prevent poor bladder com- clean intermittent self-catheterization (CISC)
pliance and the subsequent need for bladder in combination with anticholinergics (oxybu-
augmentation. tynin) is the standard therapy for children with
• Without proper management, urinary tract neurogenic bladder dysfunction with detrusor
infections and elevated bladder pressures with hyperactivity and/or DSD.
secondary bladder-wall changes may cause – CIC enables complete bladder emptying
upper urinary tract deterioration within 3 years and thus avoids bladder residues and con-
in up to 58 % of patients. sequent risks for infections.
• Urodynamic assessment has become an integral – In the high-risk bladder with DSD, CIC also
part of the initial evaluation and subsequent man- allows bladder emptying before the occur-
agement of children with neurogenic bladder. rence of otherwise “spontaneous” high-pres-
– It allows recognition of the different sub- sure voiding, which is known to be detrimental
types of NBSD for kidney function and drainage.
– It allows the prediction of which newborns are • Oxybutynin, a bladder smooth-muscle relax-
at risk for upper urinary tract deterioration ant, is used to improve bladder dynamics
– It allows proactive interventions through suppression of detrusor hypertonicity
– It allows evaluation and guidance of therapy and hyperreflexia.
– It allows early detection of neurologic – Oxybutynin eliminates (high-pressure)
deterioration uninhibited detrusor contractions (and thus
– This will minimize the deleterious effects urinary leakage)
of high intravesical pressure by directly – Prevents high-pressure bladder storage
measuring it rather than indirectly suspect- (due to detrusor hypertonicity or low blad-
ing it from the development of upper and der compliance) and high-pressure empty-
lower urinary tract changes on serial radio- ing (in case of DSD).
logic imaging. • In clinical practice, four major subtypes can
– Urodynamic risk factors are: be used to describe NBSD.
• Low bladder compliance – Type A: Sphincter overactivity combined
• Intravesical pressure more than 40 cm with detrusor underactivity
H2O – Type B: Sphincter overactivity combined
• DSD with detrusor overactivity
– Type C: Sphincter underactivity combined • Treatment efficacy can be assessed using

with detrusor underactivity clinical parameters (including CIC frequency
– Type D: Sphincter underactivity combined and volume charts), urinalysis, renal and
with detrusor overactivity bladder ultrasound, cystography, and video
• Dysfunctional type A: urodynamics.
– This is the easiest type to treat. • The long-term sequelae of insufficiently
– The bladder requires early treatment treated neurogenic bladders include renal
because of urine retention with high filling scarring, and noncompliant fibrotic bladder.
pressure and continuous leaking. To avoid these changes, it is important to
– CIC alone is effective and sufficient and follow these patients closely:
will make the bladder safe and infection – 3× yearly up to age 3 years
free, and the patient will be dry in between – 2× yearly in school-aged children
(social continence). – Yearly in adults
– Good care to empty the bladder totally is • The follow-up should include:
most important to avoid bladder infections – Urinalysis and culture
caused by residual urine. – Renal and pelvic ultrasound
• Dysfunctional type B: – Cystography to investigate unexpected
– This will have high filling and high voiding upper urinary tract infections
pressures. – Urodynamics periodically to verify the
– It is very unsafe from birth onward due to effect of treatment
DSD. – Modalities used to look at renal functions
– With oxybutynin, the overactive detrusor include nuclear imaging [dimercaptosucci-
can be “pharmacologically converted” to nate acid (DMSA) renal scan], urinary con-
an inactive reservoir (situation similar to centrating ability, and glomerular filtration
type A), which has to be emptied with CIC. rate assessment.
• Dysfunctional type C: • With early instituted and optimal treatment,
– CIC reduces the degree of incontinence the large majority of patients can be ade-
and offers much better control over urinary quately controlled without antireflux surgery
tract infections. or surgical bladder augmentation.
– To achieve continence, this type will at a • Augmentation cystoplasty is limited to a small
later age need surgical intervention on the group of patients in whom medical treatment
sphincter (e.g. sling operation). fails (persistence of high filling pressures).
– An important point is that detrusor instabil- • In patients with insufficient sphincter activity,
ity may emerge only after surgical improve- continence achievement will require bladder-
ment of outlet resistance. If this detrusor outlet surgery in addition to medical
instability would remain unrecognized and treatment.
untreated (with oxybutynin), bladder-outlet • Surgical intervention to provide a continent
surgery would have converted a “wet but stoma will facilitate self-catheterization.
safe” into a “dry but unsafe” bladder.
• Dysfunctional type D:
– The bladder leaks due to detrusor instabil- 11.8 Clean Intermittent
ity and gradually becomes unsafe due to Catheterization
secondary bladder-wall changes with
detrusor hypertrophy and loss of bladder • In children with neurogenic bladder, CIC is
compliance. the first-choice treatment to empty the bladder
– Therefore, treatment consists of CIC com- adequately (no residue, no infection) and
bined with oxybutynin and, at a later age, safely (prior to high-pressure voiding), and it
bladder-outlet surgery. is a valuable tool for achieving continence.
11.9 Anticholinergics 317
• The wide variety of used materials and tech- • Neurogenic bowel dysfunction with constipa-
niques for CIC does not seem to affect efficacy tion and fecal soiling can interfere with the
and safety as long as some basic principles are institution of a successful CIC treatment.
applied: Retained stools may mechanically impair blad-
– Proper education and training der filling, increase detrusor irritability, or con-
– Clean and atraumatic application tribute to urine retention. Stool incontinence
– Achievement of good patient compliance increases the risk of bladder contamination and
on a long-term basis. urinary tract infection. An effective bowel man-
• For education, training, and further guidance agement program is therefore needed.
during follow-up, a dedicated continence • Finally, given the high prevalence of latex
nurse is invaluable. allergy, in the spina bifida population, a strict
• CIC has been successfully used by parents latex-free approach is of extreme importance.
even in newborns and infants, becoming a part
of their everyday routine.
• Some authors prefer early institution of CIC in 11.9 Anticholinergics
all infants with NBSD, given the fact that by
the age of 3 years, CIC will be required in all • Oxybutynin:
for achieving continence, and given the diffi- – Of the anticholinergic agents available,
culties of starting CIC at toddler age. Such oxybutynin hydrochloride is most com-
early institution of CIC seems to improve fam- monly used, and long-term experience sup-
ily compliance and their ability to assist the ports its safety also in newborns and
child in coping with their disease and with infants.
CIC. – Oxybutynin is a tertiary amine with a well-
• CIC can be successfully taught to boys and documented therapeutic effect on detrusor
girls who are motivated and who have devel- hyperactivity, and its effectiveness is attrib-
oped the required dexterity, mostly around the uted to a combination of anticholinergic
age of 6 years. (M3-selective receptor subtype antago-
• The required frequency of catheterization nism), antispasmodic, local anesthetic and
depends on several factors: fluid intake, blad- calcium-channel-blocking activity.
der capacity, and bladder filling/voiding – It provides a local anesthetic effect on irri-
pressures. table bladder and direct smooth muscle
• In practice, it is recommended to catheterize relaxant effect on urinary bladder.
six times a day in infants (linked with feeding – Urodynamic studies have shown oxybu-
time) and five times a day in school-aged tynin increases bladder size, decreases fre-
children. quency of symptoms, reduces incontinence
• Although reported incidences of CIC-related and delays initial desire to void.
infection risks are variable, it is generally – Several studies have shown its efficacy for
agreed that the risk is low as long as complete decreasing the filling pressure, increasing
bladder emptying is achieved. Furthermore, the capacity of the neurogenic bladder, and
reused supplies are not related to more urinary preserving renal function.
tract infections. If symptomatic infections – Extended-release oxybutynin is also
occur, these are mainly caused by incomplete available.
bladder emptying, and CIC appliance by child – Transcutaneous extended-release oxybu-
or caregiver needs to be optimized. tynin has been shown to be well tolerated,
• To prevent urethral strictures and false pas- with few undesired anticholinergic side-
sage in boys, catheter lubrication and avoid- effects, apart from some skin reactions.
ance of forceful manipulation during catheter – Furthermore, new-generation anticholiner-
insertion are advocated. gic agents, such as darifenacin and solife-
nacin, are selective for the M3 receptor and – Parasympathetic effect reduces smooth
thus offer the potential of reduced muscle tone in the bladder.
side-effects. – Trospium is indicated to treat symptoms of
– Intravesical oxybutynin was shown to have overactive bladder (e.g., urinary inconti-
increased efficacy and reduced side effects. nence, urgency, frequency).
Compared with oral oxybutynin, intravesi- • Fesoterodine (Toviaz):
cal oxybutynin has more potent and longer- – Fesoterodine is a competitive muscarinic
acting detrusor suppressive effects with receptor antagonist.
good tolerance and should be used prior to – The antagonistic effect results in decreased
considering surgical therapies. bladder smooth muscle contractions.
– The usual dose regimen of oral oxybutynin – It is indicated for symptoms of overactive
is 0.3–0.6 mg/kg per day in three doses. bladder (e.g., urinary urge incontinence,
– In children with insufficient response or urgency, and frequency).
significant systemic side effects to oral
oxybutynin, intravesical instillation of oxy-
butynin has been shown to be a highly effi- 11.10 Botulinum Toxin Type A
cacious, reliable, and well-tolerated therapy
for children who would otherwise require • It binds to the presynaptic nerve endings of
surgical therapy. cholinergic neurons, resulting in a marked
– Intravesical oxybutynin is used in dos- reduction in bladder contractions.
ages between 0.3 and 0.6 mg/kg per day • Botulinum A toxin injections into the detrusor
in two or three doses. Given its better tol- muscle have been shown to be a potentially
erability compared with oral treatment, if valuable approach in the neurogenic overac-
required, intravesical dosages can be fur- tive bladder.
ther increased up to doses of 0.9 mg/kg • It is also associated with reduced requirement
per day. for oral medication and improved quality of
• Tolterodine L-tartrate (Detrol and Detrol LA): life.
– Tolterodine L-tartrate is a competitive mus- • Urodynamic efficacy lasts for about 6 months,
carinic receptor antagonist for overactive after which repeated injections are necessary.
bladder. • Repeated botulinum A toxin injections could
– It differs from other anticholinergic types be considered to postpone or avoid surgical
in that it has selectivity for urinary bladder procedures in the small minority of children
over salivary glands. not responding to standard therapy with CIC
– It exhibits high specificity for muscarinic and anticholinergics.
receptors and has minimal activity or affin- • However, further investigations are required,
ity for other neurotransmitter receptors and given remaining concerns about costs and
other potential targets such as calcium long-term efficacy and safety of prolonged
channels. botulinum A toxin administration.
– In clinical studies, the mean decrease in
urge incontinence episodes was 50 % and
the mean decrease in urinary frequency 11.11 Tricyclic Antidepressant
was 17 %. Drugs
• Trospium (Sanctura):
– Trospium is a quaternary ammonium com- • These drugs are used to treat major depres-
pound that elicits antispasmodic and anti- sion; however, they have an additional use that
muscarinic effects. is treatment of bladder dysfunction.
– It antagonizes acetylcholine effect on mus- • They function to increase norepinephrine and
carinic receptors. serotonin levels.
11.11 Tricyclic Antidepressant Drugs 319
• In addition, they exhibit anticholinergic and – In children with lower-grade reflux who
direct muscle relaxant effects on the urinary empty their bladders completely, treatment
bladder. may be limited to prophylactic antibiotics.
• Imipramine hydrochloride (Tofranil) – In children with high-grade reflux, CIC is
– Imipramine hydrochloride is a typical tri- started to ensure complete emptying.
cyclic antidepressant. – Children unable to empty their bladders,
– It facilitates urine storage by decreasing regardless of reflux, are treated with CIC.
bladder contractility and increasing outlet – Children with detrusor hyperreflexia (with
resistance. or without hydronephrosis) are started on
– It has alpha-adrenergic effect on the blad- anticholinergic therapy to decrease intra-
der neck and antispasmodic effect on detru- vesical pressures and possibly decompress
sor muscle. the upper urinary tracts.
– Imipramine hydrochloride has a local anes- • Reflux treated in this manner has shown
thetic effect on bladder mucosa. a dramatic response, resolving in
• Amitriptyline hydrochloride (Elavil) 30–55 % of children.
– Amitriptyline hydrochloride is a tricyclic • Avoid the Crede maneuver (voiding by
antidepressant with sedative properties. suprapubic pressure) in children with
– It increases circulating levels of norepi- reflux because it can increase pressures
nephrine and serotonin by blocking their and aggravate the degree of reflux.
reuptake at nerve endings and is ineffective • Inability to empty bladder:
for use in urge incontinence. – Because most patients with myelodyspla-
– However, it is extremely effective in decreas- sia are unable to spontaneously empty their
ing symptoms of urinary frequency in women bladders, numerous methods have been
with pelvic floor muscle dysfunction. devised to potentiate bladder emptying.
– Amitriptyline hydrochloride restores sero- – CIC on a regular basis is a safe, effective
tonin levels and helps break the cycle of method of emptying the bladder and, if per-
pelvic floor muscle spasms. formed under clean conditions, does not
• Infection: appear to significantly increase the risk of
– In the absence of reflux, patients with UTIs infection.
are treated symptomatically. – The practice of CIC has changed the treat-
– Patients with vesicoureteral reflux are often ment of and approach to patients with neu-
placed on prophylactic antibiotics to reduce rogenic bladders.
the chance of upper UTI or pyelonephritis. – Currently, urinary diversion is rarely per-
– Bacteriuria is seen in as many as 55 % of formed in pediatric patients.
patients who have received clean intermit- • Incontinence:
tent catheterization (CIC). – Medical therapy consists of anticholinergic
– Patients who are completely asymptomatic medications to increase the functional
do not need treatment. bladder volume and to reduce involuntary
• Vesicoureteral Reflux (VUR): contractions.
– VUR occurs in 3–5 % of infants with – Additionally, alpha agonists have been
myelodysplasia and is usually associated used infrequently in children to increase
with detrusor hyperreflexia or DSD. sphincter tone.
– Treatment consists of: • Impaired bowel function:
• Antibiotic prophylaxis to prevent infection – Often, children with myelodysplasia have
• Anticholinergic medications to lower disturbances of bowel as well as urinary
detrusor filling and voiding pressures function.
• A method of bladder emptying, most – This is managed most commonly with mild
commonly CIC laxatives, such as mineral oil, combined
with enemas or digital stimulation to facili- – Dextranomer/hyaluronic acid (Deflux)

tate removal of bowel contents. injection
– Constipation can affect bladder emptying • This is a much less invasive way to
adversely address vesicoureteral reflux.
– The need for a program to combat consti- • Deflux (a viscous gel consisting of dex-
pation by maintaining soft stools and facili- tranomer microspheres and hyaluronic
tating complete evacuation of bowel acid) is injected cystoscopically just
contents is an integral part of treatment in beneath the ureteral orifice to prevent
children with myelodysplasia. reflux.
• Consider all patients with myelodysplasia of • It is performed as an outpatient pro-
spina bifida to have a latex allergy and make cedure with excellent success rates
every effort to avoid exposure to latex from (70–85 % with a single injection) and
birth. Gloves, catheters, crib pads, and bottle can be repeated if necessary.
nipples are all potential sources and may exac- – Vesicostomy
erbate hypersensitivity. • In infants who cannot be catheterized or
who demonstrate worsening renal func-
tion despite medical therapy and CIC,
11.12 Surgical Management cutaneous vesicostomy can be per-
formed to establish adequate bladder
• Surgery for neurogenic bladder, although once drainage.
performed on most patients, is now primarily • Vesicostomy is an effective temporary
reserved for patients: procedure that may be reversed at any
– Who have progressive renal damage time.
despite maximal medical therapy • Bladder augmentation:
– With extremely noncompliant bladders – Bladder augmentation is an option in
– Who wish to improve their continence patients with small bladder capacity and
• Most procedures are designed to allow ade- poor bladder compliance despite maximal
quate low-pressure bladder storage (thereby medical therapy.
protecting the upper urinary tract), to correct – The bladder capacity is increased by anas-
persistent reflux and prevent renal scarring, or tomosing a detubularized segment of bowel
to aid with continence. to the bladder. As a result of this, the stor-
• Procedures to correct vesicoureteral reflux: age pressures can be lowered, minimizing
– Ureteral reimplantation upper urinary tract deterioration and
• Ureteral reimplantation can be per- improving continence.
formed in patients with recurrent symp- – This can be associated with complications
tomatic UTIs despite adequate bladder including metabolic derangements,
drainage and antibiotic prophylaxis or in mucous production, stone formation, and
patients with persistent high-grade reflux hematuria.
with demonstrated renal scarring. – If incontinence is a significant problem, a
• The purpose of the procedure is to cre- bladder neck sling procedure can be per-
ate a nonrefluxing connection between formed along with bladder augmentation.
the ureter and the bladder. • Urinary diversion:
• This treatment is very effective, pro- – Formal urinary diversion for neurogenic
vided that a regimen is implemented to bladder is very rarely performed today.
ensure a low-pressure reservoir and – The risks of major abdominal surgery, met-
bladder emptying. abolic derangements, and long-term upper
Further Reading 321
urinary tract deterioration are present with • In this procedure, stem cells are cysto-
urinary diversion. scopically injected into the urinary
– Since the advent of CIC, some patients sphincter.
who underwent incontinent urinary diver- • The goal of therapy is to increase
sion as infants have undergone successful sphincter activity and improve
undiversion with bladder augmentation. continence.
• Procedures for incontinence:
– As patients get older, continence becomes
an issue in their lives. Further Reading
– Several procedures have been developed to
improve continence, with the hope to pro- 1. Amark P, Bussman G, Eksborg S. Follow-up of long-
time treatment with intravesical oxybutynin for neu-
mote more-independent living.
rogenic bladder in children. Eur Urol. 1998;34:
– Dextranomer/hyaluronic acid (Deflux) 148–53.
bladder neck injection 2. Apostolidis A, Dasgupta P, Denys P, Elneil S,
• This procedure consists of cystoscopi- Fowler CJ, Giannantoni A, et al. Recommendations
on the use of botulinum toxin in the treatment of
cally injecting dextranomer/hyaluronic
lower urinary tract disorders and pelvic floor dys-
acid into the bladder neck to increase functions: a European consensus report. Eur Urol.
outlet resistance. 2009;55(1):100–19.
• It has been shown to improve conti- 3. Baskin LS, Kogan BA, Benard F. Treatment of infants
with neurogenic bladder dysfunction using anticho-
nence, but complete cures are unpredict-
linergic drugs and intermittent catheterisation. Br
able and the durability of the procedure J Urol. 1990;66:532–4.
is still being evaluated. 4. Buyse G, Verpoorten C, Vereecken R, Casaer P.
– Bladder neck sling Treatment of neurogenic bladder dysfunction in
infants and children with neurospinal dysraphism
• This procedure entails placing a sling of
with clean intermittent (self) catheterisation and opti-
either autologous tissue or synthetic mized intravesical oxybutynin hydrochloride therapy.
polypropylene mesh beneath the urethra Eur J Pediatr Surg. 1995;5:31–4.
in order to increase outlet resistance. 5. Buyse G, Waldeck K, Verpoorten C, Björk H, Casaer
P, Andersson KE. Intravesical oxybutynin for neuro-
• There are several variations to the proce-
genic bladder dysfunction: less systemic side effects
dure, but overall success rates range from due to reduced first pass metabolism. J Urol.
60 % to greater than 85 %, with a number 1998;160:892–6.
of patients becoming fully continent. 6. De Wachter S, Wyndaele JJ. Intravesical oxybutynin:
a local anesthetic effect on bladder C afferents. J Urol.
– Detrusor myoplasty
2003;169:1892–5.
• Though uncommon, this procedure has 7. Edelstein RA, Bauer SB, Kelly MD, Darbey MM,
the possibility of increasing bladder Peters CA, Atala A, Mandell J, Colodny AH, Retik
contractility in some patients. AB. The long-term urological response of neonates
with myelodysplasia treated proactively with inter-
• It is performed by harvesting the
mittent catheterization and anticholinergic therapy.
patient’s latissimus dorsi muscle and J Urol. 1995;154:1500–4.
microsurgically transplanting it so that 8. Fernandes E, Reinberg Y, Vernier R, Gonzales R.
it wraps around the bladder. Neurogenic bladder dysfunction in children: review of
pathophysiology and current management. J Pediatr.
• This has allowed some patients to spon-
1994;124:1–7.
taneously void and reduce their depen- 9. Frenkl TL, Rackley RR. Injectable neuromodulatory
dence on catheterization. agents: botulinum toxin therapy. Urol Clin N Am.
– Stem cell injection 2005;32(1):89–99.
10. Goessl C, Sauter T, Michael T, Bergé B, Staehler M,
• This is still purely experimental, but
Miller K. Efficacy and tolerability of tolterodine in
preliminary studies have shown some children with detrusor hyperreflexia. Urology. 2000;
promise. 55:414–8.
11. Jeruto A, Poenaru D, Bransford R. Clean intermittent 16. Madersbacher H. Neurogenic bladder dysfunction in
catheterisation: overview of results in 194 patients patients with myelomeningocele. Curr Opin Urol.
with spina bifida. Afr J Pediatr Surg. 2004;1:20–3. 2002;12:469–72.
12. Kaefer M, Pabby A, Kelly M, Darbey M, Bauer SB. 17. McKibben MJ, Seed P, Ross SS, Borawski KM.
Improved bladder function after prophylactic treat- Urinary tract infection and neurogenic bladder. Urol
ment of the high risk neurogenic bladder in new- Clin N Am. 2015;42(4):527–36.
borns with myelomeningocele. J Urol. 1999;162: 18. Snodgrass WT, Adams R. Initial urologic manage-
1068–71. ment of myelomeningocele. Urol Clin N Am.
13. Kasabian NG, Bauer SB, Dyro FM, Colodny AH, 2004;31:427–34.
Mandell J, Retik AB. The prophylactic value of clean 19. Sutherland RS, Kogan BA, Baskin LS, Mevorach RA.
intermittent catheterization and anticholinergic medi- Clean intermittent catheterization in boys using the
cation in newborns and infants with myelodysplasia at LOFric catheter. J Urol. 1996;156:2041–3.
risk of developing urinary tract deterioration. Am 20. van Gool JD, Dik P, de Jong TP. Bladder sphincter
J Dis Child. 1992;146:840–3. dysfunction in myelomeningocele. Eur J Pediatr.
14. Kessler TM, Lackner J, Kiss G, Rehder P, 2001;160:414–20.
Madersbacher H. Early proactive management 21. Wein AJ, Rackley RR. Overactive bladder: a better
improves upper urinary tract function and reduces the understanding of pathophysiology, diagnosis and
need for surgery in patients with myelomeningocele. management. J Urol. 2006;175(3 Pt 2):S5–10.
Neurourol Urodyn. 2006;25:758–62. 22. Zegers B, Uiterwaal C, Kimpen J, et al. Antibiotic
15. Kurzrock EA, Polse S. Renal deterioration in myelo- prophylaxis for urinary tract infections in children
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cal correlates. J Urol. 1998;159:1657–61. J Urol. 2011;186(6):2365–71.
Urinary Tract Infection in Infants
and Children 12
12.1 Introduction – The most common pathogen is Escherichia

coli, accounting for approximately 85 % of
• Urinary tract infection (UTI) is one of the urinary tract infections in children.
most common infections in infants and – Klebsiella, Proteus, Enterobacter,
children. Citrobacter, Staphylococcus saprophyti-
• The occurrences of symptomatic UTI for the cus, and Enterococcus.
first time in boys and girls is highest during – Other organisms that can cause urinary
the first year of life and decreases markedly tract infection include fungi (Candida spe-
after that. cies) and viruses.
• The workup of infants who present with fever • The incidence of UTIs varies based on age,
should include evaluation for urinary tract sex, and gender.
infection. • The exact incidence of UTIs is not known but
• Urinary tract infection (UTI) in infants and in the United States UTIs are estimated to
children is divided into two categories: affect 2.4–2.8 % of children.
– Upper urinary tract infection • The overall prevalence of UTI in infants pre-
(Pyelonephritis) senting with fever was 7.0 %.
– Lower urinary tract infection (Cystitis) • Approximately 7 % of children 2–24 months
• Most episodes of UTI during the first year of of age presenting with fever without a source
life are pyelonephritis. were diagnosed with a UTI.
• It is not uncommon for infants younger than • 8 % of children 2–19 years of age presenting
3 months to present with fever without a with possible urinary symptoms were diag-
localizing source and these patients should be nosed with a UTI.
evaluated for UTI. • The frequency of UTIs is also variable accord-
• After age 2 years, UTI in the form of cystitis is ing to age and sex. The rates of UTIs in girls
common among girls. according to age as follows:
• Rarely, UTI maybe the first presentation of an – 0–3 months (7.5 %)
important underlying structural or neurogenic – 3–6 months (5.7 %)
abnormality of the urinary tract. – 6–12 months (8.3 %)
• The most common causative organisms are – >12 months (2.1 %)
bowel flora, typically gram-negative rods. • In boys, the incidence of UTIs is also influ-
– Escherichia coli is the most common enced by whether the child is circumcised or
organism. not.

324 12 Urinary Tract Infection in Infants and Children
– The rate in uncircumcised febrile boys • The reference standard for the diagnosis of
<3 months of age was 20.7 % UTI is a single organism cultured from a
– The rate in circumcised febrile boys specimen obtained at the following
<3 months of age was 2.4 % concentrations:
– The rate in uncircumcised febrile boys – Suprapubic aspiration urine specimen,
6–12 months of age was 7.3 % greater than 1,000 colony-forming units
– The rate in circumcised febrile boys per mL
6–12 months of age was 0.3 % – Catheter urine specimen, greater than
– However, contamination is very common 10,000 colony-forming units per mL
in obtaining a urine sample from a male – Clean-catch, midstream urine specimen,
when the foreskin cannot be retracted and 100,000 colony-forming units per mL or
the rates in uncircumcised males are, greater.
undoubtedly, overestimates. • Urological abnormalities known to be associ-
• During the first few months of life, the inci- ated with URIs:
dence of UTI in boys exceeds that in girls. – Baseline abnormalities of the urogenital
• By the end of the first year and thereafter, first- tract have been reported in up to 3.2 % of
time and recurrent UTIs are most common in healthy, screened infants.
girls. – Obstructive anomalies are found in up to
• The incidence of UTI in children aged 4%
1–2 years is 8.1 % in girls and 1.9 % in boys. – Vesicoureteral reflux in 8–40 % of children
• In a study of infants presenting to pediatric being evaluated for their first UTI.
emergency departments, the prevalence of – Children younger than 2 years may be at
UTI in infants younger than 60 days with a greater risk of parenchymal defects than
temperature greater than 100.4 °F (38 °C) was older children.
9 %.
• Guidelines from the American Academy of
Pediatrics recommend considering the 12.2 Etiology
diagnosis of UTI in patients aged 2 months
to 2 years who present with unexplained • Bacterial infections are the most common
fever. cause of UTI in infants and children.
• Acute urinary tract infections are relatively • E coli is the most frequent organism causing
common in children, with 8 % of girls and 2 % UTI responsible for 75–90 % of UTIs.
of boys having at least one episode of UTIs by • Other bacterial organisms that cause UTI
7 years of age. include:
• Renal parenchymal defects are present in – Klebsiella species
3–15 % of children within 1–2 years of their – Proteus species
first diagnosed urinary tract infection. – Enterococcus species
• Clinical signs and symptoms of a urinary tract – Staphylococcus saprophyticus
infection depend on the age of the child, but – Streptococcus group B, especially among
all febrile children 2–24 months of age with neonates
no obvious cause of infection should be evalu- – Pseudomonas aeruginosa
ated for urinary tract infection. • Other relatively rare organisms responsible
• Prophylactic antibiotics do not reduce the risk for UTIs include Fungi (Candida species) and
of subsequent urinary tract infections, even in viruses (Adenovirus)
children with mild to moderate vesicoureteral • Adenovirus is a rare cause of hemorrhagic
reflux. cystitis.
• Constipation should be avoided to help pre- • Genes that are possibly responsible for
vent urinary tract infections. increased susceptibility to recurrent UTIs
include HSPA1B, CXCR1, CXCR2, TLR2, • Normally, urine in the proximal urethra and
TLR4, and TGFβ1. urinary bladder is sterile.
• Susceptibility to UTI may be increased by any • Access of microorganisms to the urethra and
of the following factors: urinary bladder can result from several factors
– Alteration of the periurethral flora by anti- including:
biotic therapy – Stasis and turbulent urine flow during nor-
– Anatomic anomalies of the renal system mal voiding
leading to urinary stasis – Voiding dysfunction
– Bowel and bladder dysfunction – Urethral catheterization
– Constipation – Colonization of organisms during episodes
• The use of antibiotics for other infections of sepsis
increases the risk for UTIs. – Direct spread from the perineum
• The use of antibiotics alter the gastrointestinal • The short female urethra and its proximity to
and periurethral flora, disturbing the urinary fecal flora may, in part, explain the predomi-
tract’s natural defense against colonization by nance of UTI in girls after the neonatal period.
pathogenic bacteria. • Mortality related to UTI is exceedingly rare in
• Neurogenic or anatomic abnormalities of the otherwise healthy children.
urinary bladder may also cause voiding • Cystitis may cause voiding symptoms but it is
dysfunction. not associated with long-term kidney
• Anatomic abnormalities of the renal system damage.
are known to predispose to UTIs. • Approximately 10–30 % of children with UTI
• Constipation, with the rectum chronically develop some renal scarring.
dilated by feces, is an important cause of void- • Long-term complications of pyelonephritis
ing dysfunction and UTIs. are:
• For male infants, neonatal circumcision sub- – Renal parenchymal scarring
stantially decreases the risk of UTI. – Hypertension
– The Risk is particularly high during the – Impaired renal function
first 3 months of life. – End-stage renal disease
– It was shown that during the first year of
life, the rate of UTI was 2.15 % in uncir-
cumcised boys, versus 0.22 % in circum- 12.4 Clinical Features
cised boys.
– In another study, it was shown that in • A urinary tract infection (UTI), is divided into
febrile boys younger than 3 months, UTI two types depending on the level of infection.
was present in 2.4 % of circumcised boys • Acute cystitis or bladder infection, is an infec-
and in 20.1 % of uncircumcised boys. tion that affects the lower urinary tract.
• Acute pyelonephritis (infection of the kidney),
is an infection that affects the upper urinary
12.3 Pathophysiology tract.
• All febrile children between 2 and 24 months
• UTIs result when colonized organisms in the of age with no obvious cause of infection
periurethral area ascend into the bladder via should be evaluated for UTI, with the excep-
the urethra to cause cystitis. tion of circumcised boys older than 12 months.
• From the bladder, organisms can spread up the • Older children who present with fever should
urinary tract to the kidneys and cause be evaluated for UTI if the clinical presenta-
pyelonephritis. tion points toward a urinary source.
• Sometimes, the organisms can spread to the • The clinical features of patients with UTIs are
bloodstream and cause bacteremia or septicemia. variable and differ according to the patient’s age.
• Neonates and infants up to age 2 months who resolves without permanent damage, but high-
have pyelonephritis usually do not have symp- grade (grade 4–5) VUR may require surgical
toms localized to the urinary tract and UTI is correction.
discovered as part of an evaluation for neona- • Physical examination findings can be nonspe-
tal sepsis. cific but may include suprapubic tenderness or
• Boys are at increased risk of UTI if younger costovertebral angle tenderness.
than 6 months, or if younger than 12 months • Neonates with UTI may present with the fol-
and uncircumcised. lowing symptoms:
• Girls are generally at an increased risk of UTI, – Jaundice
particularly if younger than 1 year. – Fever
• Infants from 2 to 36 months of age with a – Failure to thrive
fever of >39 °C and no other source for fever – Poor feeding
on history or physical examination could have – Vomiting
a UTI, and should have urine collected for uri- – Irritability
nalysis. Unless this test is completely normal, • Infants and children aged 2 months to 2 years
they should then have urine collected by cath- lack symptoms localized to the urinary tract
eter or suprapubic aspirate and sent for but may present with the following
culture. symptoms:
• When UTI is suspected in toilet-trained chil- – Poor feeding
dren, a midstream urine sample rather than a – Fever
catheter or suprapubic aspiration specimen – Loss of appetite, poor oral intake and
should be submitted for urinalysis and vomiting
culture. – Strong and foul smelling urine
• Children with possible UTI who require anti- – Abdominal pain or suprapubic pain
biotic treatment immediately for other indica- – Irritability
tions, such as suspected bacteremia, should – Voiding symptoms suggestive of cystitis,
have urine collected for urinalysis, micros- with crying on urination
copy and culture. The test sample should be • Children aged 2–6 years may present with the
midstream urine if the child is toilet trained, following symptoms:
and a catheter or suprapubic aspiration or – Vomiting
clean-catch specimen if not, and obtained – Abdominal, flank, back pain or suprapubic
before starting antibiotics. pain
• Over diagnosis of UTI is a common problem, – Loss of appetite
leading to overuse of antibiotics and unneces- – Irritability
sary imaging. – Fever
• Urines collected by bag should never be used – Strong and foul smelling urine
for diagnosis of UTI. Urines with low colony – Enuresis
counts, mixed growth or no pyuria are usually – Dysuria, urgency, frequency
contaminated. • Children older than 6 years may present with
• Children <2 years of age should be investi- the following symptoms:
gated after their first febrile UTI with a renal – Fever
and bladder ultrasound to identify significant – Vomiting
renal abnormalities and grade IV or V VUR. – Abdominal pain
• A voiding cystourethrogram (VCUG) is not – Flank/back pain
indicated with a first febrile UTI when the – Strong and foul smelling urine
renal and bladder ultrasound is normal. – Dysuria, urgency, frequency
• VCUG may detect vesicoureteric reflux – Enuresis
(VUR). Low-grade VUR (grade 1–2) usually – Incontinence
• Older children with pyelonephritis often have • Dipstick tests for blood and protein have
tenderness of the flank or costovertebral poor sensitivity and specificity in the
angle. detection of UTI and may be
• Those with cystitis may have suprapubic ten- misleading.
derness with or without a palpable bladder. • Automated microscopy has better speci-
• The finding of hypertension should raise sus- ficity and likelihood ratios than dipstick
picion of hydronephrosis or renal parenchyma testing, but it had slightly lower
disease. sensitivity.
– The nitrite test:
• This measures the conversion of dietary
12.5 Investigations and Diagnosis nitrate to nitrite by Gram-negative
bacteria.
• Complete blood count (CBC) • A positive nitrite test makes UTI very
• Blood cultures (in patients with suspected likely.
bacteremia or urosepsis) • The test may be falsely negative if the
• Serum creatinine and blood urea nitrogen bladder is emptied frequently or if an
• Serum electrolyte levels organism that does not metabolize
• The diagnosis of a urinary tract infection in nitrate (including all Gram-positive
children depends on a positive urinary organisms) is the cause of infection.
culture. • The test for nitrite is more specific but
• Contamination poses a frequent challenge less sensitive.
depending on the method of urine collection – The leukocyte esterase test:
used. • This is an indirect measure of pyuria
• A blood culture in febrile infants and older and, therefore, may be falsely negative
patients who are clinically ill, toxic, or when leukocytes are present in low
severely febrile. concentration.
• Urine analysis: • Leukocyte esterase is the most sensitive
– Urinalysis alone is not sufficient for diag- single test in children with a suspected
nosing UTI. UTI.
– However, urinalysis can help in identifying • A negative leukocyte esterase result
febrile children who should receive anti- greatly reduces the likelihood of UTI,
bacterial treatment while culture results whereas a positive nitrite result makes it
from a properly collected urine specimen much more likely; the converse is not
are pending. true, however.
– Rapid urine tests (also known as dipsticks – A microscopic urinalysis:
or macroscopic urinalysis) remain useful • This is useful to determine whether
for the diagnosis of UTI. there are white blood cells in the
– Urine dipstick test: urine, which is a sensitive indicator
• Urine dipstick testing alone may pro- of inflammation associated with
vide an adequate initial UTI screen. infection.
• Urine dipstick tests for UTI include leu- • Microscopic examination of spun urine
kocyte esterase, nitrite, blood, and can evaluate for the presence of white
protein. blood cells (WBCs), red blood cells
• Positive dipstick readings for nitrite, (RBCs), bacteria, casts, and skin con-
leukocyte esterase, or blood may sug- tamination (e.g., epithelial cells).
gest a UTI. • Approximately 10–20 % of pediatric
• Dipstick tests have sensitivities of patients with UTIs have normal urinaly-
approximately 85–94 %. sis results.
• Pyuria is 73 % sensitive and 81 % spe- – Urine collection must be done before start-
cific for the diagnosis of UTI. ing antibiotics because a single dose of an
• However, the definition of pyuria is not effective antibiotic rapidly sterilizes the
uniform in the literature. urine.
• The finding of ten white blood cells per – Microscopy and urine culture should be
microliter in uncentrifuged urine speci- performed in children younger than 3 years
men is reported to be a more sensitive instead of dipstick testing.
indicator of UTI. – The American Academy of Pediatrics
• Or, the finding of >5 white blood cells (AAP) criteria for the diagnosis of UTI in
per high-power field in uncentrifuged children 2–24 months are the presence of
urine specimen is a more sensitive indi- pyuria and/or bacteriuria on urinalysis and
cator of UTI. of at least 50,000 colony-forming units
• The presence of pyuria of at least ten (CFU) per mL of a uropathogen from the
white blood cells per high-power field quantitative culture of a properly collected
and bacteriuria are recommended as the urine specimen.
criteria for diagnosing UTI with – In neonates younger than 2 months of age,
microscopy. the criteria for the diagnosis of UTI include
• The absence of pyuria does not exclude the presence of lower amounts of a single
a UTI, especially in infants <2 months pathogen (10,000–50,000 CFU/mL)
of age. – The use of “urine bags” to collect samples
• The question is whether infants with is discouraged due to the high rate of con-
positive urine cultures but no pyuria tamination when cultured, and catheter-
have contamination or asymptomatic ization is preferred in those not toilet
bacteruria rather than a UTI. trained.
• Bacteria and yeast seen on microscopic – Urine sample for culture:
urinalysis are often contaminants. • A midstream, clean-catch specimen
• The combination of pyuria and bacter- may be obtained from children who
uria on urinalysis should raise suspicion have urinary control.
for a UTI. • Suprapubic aspiration or urethral cathe-
• On a suprapubic aspirate, the presence terization should be used in infants or
of five or more WBCs per high-power children unable to void on request.
field or the presence of ten or more • Suprapubic aspiration is the method of
WBC/μL suggests an infection. Gram choice for obtaining urine from the fol-
stain of unspun urine may reveal lowing patients:
organisms. – Uncircumcised boys with a redun-
• A hemacytometer measures cells per dant or tight foreskin
volume and has been found to be more – Girls with tight labial adhesions,
sensitive and specific than standard – Children of either sex with clinically
microscopic examination. significant periurethral irritation
• The combination of hemacytometer cell – The diagnosis of UTIs in infants and chil-
count and Gram stain has been shown in dren is based on colony-forming units
studies to have a sensitivity approaching (CFU) per mL of an uropathogen depend-
95 %. ing on the method used to collect the urine
– A child with a negative urine dipstick for sample.
nitrites and leukocyte esterase and no • 105 CFU/mL is used for a “clean-catch”
pyuria or bacteruria on microscopic exami- mid-stream urine sample
nation has a <1 % chance of having a UTI. • 104 CFU/mL is used for catheter-
• Urine culture and sensitivity: obtained urine specimens
• 102 CFU/mL is used for suprapubic episode of cystitis or for those with a first
urine aspirations febrile UTI.
– In young children, urine samples collected – Imaging should only be performed when it
with a bag are unreliable compared with is likely to alter management.
samples collected with a catheter. – The choice of imaging should be guided by
Therefore, in a child who is unable to pro- the safety, cost and accuracy of the proce-
vide a clean-catch specimen, catheteriza- dure to be done.
tion should be considered. If urine cannot – Current common imaging options for chil-
be cultured within 4 h of collection, the dren with UTI include renal/bladder ultra-
sample should be refrigerated. sound (RBUS), radiographic (e.g., VCUG)
– Culture of a urine specimen from a sterile and radioisotope (e.g., dimercaptosuccinic
bag attached to the perineal area has a acid [DMSA]) techniques.
false-positive rate so high that this method • Ultrasonography of the urinary tract:
of urine collection is not suitable for – Ultrasonography is the imaging study of
diagnosing UTI. However, a culture of a choice in children with UTI.
urine specimen from a sterile bag that – Urinary ultrasonography is safe, cheap,
shows no growth is strong evidence that noninvasive study, radiation free and easy
UTI is absent. to perform.
– Multiple organisms may be present in – The AAP Clinical Practice Guidelines rec-
patients with structural abnormalities. ommend routine ultrasonography of the
• In previously well children who have not been urinary tract after a first febrile UTI in chil-
on antibiotics, UTIs are usually due to: dren aged 2–24 months.
– Escherichia coli – Other indications for ultrasonography of
– Klebsiella pneumoniae the urinary tract after a febrile UTI in pedi-
– Enterobacter species atric patients are as follows:
– Citrobacter species • Delayed or unsatisfactory response to
– Serratia species treatment of a first febrile UTI
– In adolescent females only, Staphylococcus • An abdominal mass or abnormal void-
saprophyticus ing (dribbling of urine)
• Mixed growth or growth of other organisms • Recurrence of febrile UTI after a satis-
usually indicates that the urine is factory response to treatment
contaminated. • Finally, renal ultrasonography should be
• When children are started on antibiotics for considered for any child with a first
possible UTI, the diagnosis must be reas- febrile UTI in whom good follow-up
sessed once the results of all investigations are cannot be ensured.
available and antibiotics stopped if UTI • Voiding Cystourethrography (VCUG):
appears to be unlikely. – Traditionally, VCUG has been recom-
• The American Academy of Pediatrics recommended for infants and children after a first
mends renal ultrasound and voiding cystoure- febrile UTI.
throgram in all children less than 2 years old – This is based on assumptions that most
who have had a urinary tract infection. upper UTIs occur because of urinary blad-
• The National Institute for Health and Care der infection and that vesicoureteral reflux
Excellence only recommends routine imaging (VUR) transfers bacteria in the bladder to
in those less than 6 months old or who have the kidney.
unusual findings. – The AAP no longer recommends the rou-
• Imaging studies: tine use of VCUG after the first UTI.
– In general imaging studies are not indi- – There is some concern, however, that with-
cated for infants and children with a first out VCUG after the first documented
febrile UTI, some cases of significant – A VCUG is usually indicated for children
reflux disease will be missed. <2 years of age with a second well-
– VCUG is recommended after a second epi- documented UTI.
sode of febrile UTI. • Where available, a nuclear cystogram (NCG)
– VCUG is indicated if renal and bladder may be used in place of a VCUG to assess for
ultrasonography reveals: VUR using radioisotopes.
• Hydronephrosis – NCG delivers less radiation than a VCUG
• Renal scarring but is less readily available and provides
• Obstructive uropathy poor anatomical detail for the male
• Masses or if complex medical condi- urethra.
tions are associated with the UTI. – NCG can miss posterior urethral valves.
• Other findings suggestive of high-grade – NCG can be used in place of VCUG as the
VUR initial test for VUR investigation in females
– VCUG should also be performed if a and in follow-up studies for both sexes.
patient has a recurrence of a febrile UTI, • A DMSA scan:
even if previous ultrasonographic examina- – This can be used to diagnose acute pyelo-
tion findings were unremarkable. nephritis (when performed during acute ill-
– Children who respond to treatment for a ness) and to identify renal scars (when
UTI but afterwards demonstrate an abnor- performed months following the acute
mal voiding pattern may need to undergo illness).
an evaluation for voiding dysfunction. This – DMSA scan is associated with radiation
evaluation may include standard VCUG. exposure and is not likely to alter manage-
– In the past, a voiding cystourethrogram ment; thus, a DMSA is primarily useful
(VCUG) was recommended routinely for when the diagnosis of acute UTI or of
children between 2 months and 2 years of repeated UTIs is in doubt.
age who had a febrile UTI, but this is no
longer recommended practice.
– A VCUG is the optimal method for diag- 12.6 Management
nosing VUR and for assessing the degree
of VUR and the anatomy of the male • According to AAP guidelines for the treat-
urethra. ment of initial UTIs in febrile infants and chil-
– There are several drawbacks to performing dren aged 2–24 months old, antibiotics can be
a VCUG including expense, exposure to given orally or parenterally, with the choice of
radiation, and the risk of causing a UTI and route based on practical considerations.
discomfort for the child. • Oral antibiotics should not be used in a child
– A recent change in practice is that antibi- who is acutely ill or toxic, has persistent vom-
otic prophylaxis is no longer recommended iting, or has moderate to severe dehydration.
for children with grade I through III VUR Daily follow-up and good compliance are
because the number needed to receive pro- essential with this approach.
phylaxis for 1 year to prevent one UTI is • The AAP recommends basing the choice of
small. Therefore, routine imaging of infants antibiotic on local sensitivity patterns if
with VCUG after the first UTI is no longer known.
suggested unless abdominal ultrasound is • The choice can be adjusted, if necessary, when
suggestive of renal abnormalities or results of sensitivity testing become
obstruction, or high-grade VUR. A child available.
with normal kidney structure is not at sig- • Antibiotics can be given for 7 or 14 days.
nificant risk of developing chronic kidney • Amoxicillin has traditionally been a first-line
disease because of UTIs. antibiotic for UTI, but increased rates of E.
12.6 Management 331
coli resistance have made it a less acceptable Antibiotics used for oral treatment of a urinary tract
choice. infection
• Studies have found higher cure rates with trim- Antibiotic Dose
ethoprim/sulfamethoxazole (Bactrim, Septra). Cefpodoxime 10 mg/kg divided
q12 h
• Other choices include amoxicillin/clavulanate
Cefixime (Suprax) 8 mg/kg q24 h or
(Augmentin) or cephalosporins, such as cefix- divided q12 h
ime (Suprax), cefpodoxime, cefprozil (Cefzil), Nitrofurantoin 5–7 mg/kg divided
or cephalexin (Keflex). q6 h
• Patients with a nontoxic appearance may be Cefprozil (Cefzil) 30 mg/kg divided
treated with oral fluids and antibiotics. Toxic- q12 h
appearing patients must be aggressively
treated with intravenous (IV) fluids and paren-
teral antibiotics. • A Cochrane review of children up to
• Most cases of uncomplicated UTI respond 18 years of age with pyelonephritis found
readily to outpatient antibiotic treatments no difference between oral antibiotics (10–
without further sequelae. 14 days) and IV antibiotics (3 days) fol-
• Antibiotic resistance among uropathogens is lowed by oral antibiotics (10 days) with
increasing dramatically, however. respect to duration of fever or subsequent
• Previous antibiotic exposure (i.e., for otitis renal damage.
media) has been found to be associated with • Similarly, no significant differences were
drug-resistant UTIs and should be kept in found comparing IV antibiotics (3–4 days)
mind when choosing empiric therapy. followed by oral antibiotics, versus IV antibi-
• Children with acute pyelonephritis can be otics alone for 7–14 days.
treated effectively with either oral antibiotics • Most experts recommend initial treatment
or with 2–4 days of IV therapy followed by with oral antibiotics for febrile UTIs in
oral therapy. Oral therapy with a third- nontoxic children with no known structural
generation cephalosporin was as effective as urological abnormality, assuming that they
traditional inpatient parenteral treatment. are likely to receive and tolerate every
dose.
Antibiotics used for oral treatment of a urinary tract • Data on oral therapy is limited for infants
infection
2–3 months of age, so close follow-up is war-
Antibiotic Dose
ranted for this age group. Some experts
Sulfamethoxazole and 30–60 mg/kg SMZ,
trimethoprim (SMZ-TMP) 6–12 mg/kg TMP recommend initial IV antibiotics for this age
(Bactrim, Septra) divided q12 h group.
(8–10 mg/kg divided • While waiting for antibiotic susceptibility
q12 h) results for the likely bacterial pathogen, clini-
Amoxicillin 50 mg/kg/day cians should make an empirical choice of anti-
(divided in three biotics based on local susceptibility patterns.
doses)
Aminoglycoside levels and renal function
Amoxicillin and clavulanic *20–40 mg/kg
acid (Augmentin) divided q8 h need to be monitored when the aminoglyco-
*25–45 mg/kg side is continued for >48 h.
divided q12 h • If clinical findings indicate that immediate
Cephalexin (Keflex) *50–100 mg/kg antibiotic therapy is indicated, a urine speci-
divided q6 h men for urinalysis and culture should be
*25–50 mg/ kg obtained before treatment is started.
divided q6–12 h
• Common choices for empiric oral treatment
Ciprofloxacin 30 mg/g/day (divided
in two doses) are:
– A second- or third-generation cephalosporin
– Amoxicillin/clavulanate, or sulfamethoxazole- procedure for families who choose it.” The

trimethoprim (SMZ-TMP). AAP notes that the benefits of the procedure
• Patients with a nontoxic appearance may be include prevention of UTIs.
treated with oral fluids and antibiotics. • Children with acute pyelonephritis can be
• Hospitalization is necessary for the following treated effectively with oral antibiotics (e.g.,
patients with UTI: amoxicillin/clavulanate, cefixime, ceftibuten
– Patients who are toxemic or septic [Cedax]) for 10–14 days or with short-courses
– Patients with signs of urinary obstruction (2–4 days) of intravenous therapy followed by
or significant underlying disease oral therapy for a total of 10–14 days.
– Patients who are unable to tolerate ade- • Follow-up assessment to confirm an appropri-
quate oral fluids or medications ate clinical response should be performed
– Infants younger than 2 months with febrile 48–72 h after initiating antimicrobial therapy
UTI (presumed pyelonephritis) in all children with UTI.
– All infants younger than 1 month with sus- • Culture and susceptibility results may indicate
pected UTI, even if not febrile that a change of antibiotic is necessary.
• Antibiotics suggested for parenteral treatment • If expected clinical improvement does not
are as follows: occur, consider further evaluation.
– Ceftriaxone • Infants <8 weeks old:
– Cefotaxime – The diagnosis in infants <8 weeks old with
– Ampicillin a febrile UTI is usually based on fever and
– Gentamicin on positive results from a urine specimen
• Infants and children with febrile UTI should obtained by catheterization.
be treated with antibiotics for 7–10 days. – In this age 10,000 colonies/mm3 defines
• Oral antibiotics can be administered as ini- bacteriuria.
tial treatment when the child has no other – Infants with such findings are usually hos-
indication for admission to hospital and is pitalized and receive parenteral antibiotic
considered likely to receive and tolerate therapy.
every dose. – However, clinical judgment may indicate
• There is no evidence that children with UTIs that home treatment is appropriate.
and documented bacteremia who have a rapid – Parenteral antibiotics may be used with
clinical response to antibiotics require intrave- daily follow-up until the patient is afebrile
nous antibiotics or a longer course of for 24 h.
antibiotics. – Complete 10–14 days of therapy with an
• The choice of antibiotics should be guided by oral antibiotic that is active against the
the resistance pattern of common urinary infecting bacteria.
pathogens in the community and changed to a • Children with cystitis:
less broad spectrum agent, if practical, when – Children with cystitis usually do not require
the sensitivity of the pathogen is known. special medical care other than appropriate
• Consider circumcision of male neonates to antibiotic therapy and symptomatic treat-
prevent UTIs. ment if voiding symptoms are marked.
• A systematic review concluded that routine – Antibiotic therapy is started on the basis of
circumcision in boys does not reduce the risk clinical history and urinalysis results before
of UTI enough to justify the risk of surgical the diagnosis is documented.
complications. – A 4-day course of an oral antibiotic agent
• The AAP policy statement on circumcision is is recommended for the treatment of
that “the health benefits of newborn male cir- cystitis.
cumcision outweigh the risks and that the pro- – Nitrofurantoin can be given for 7 days or
cedure’s benefits justify access to this for 3 days after obtaining sterile urine.
12.6 Management 333
– A 2- to 4-day course of oral antibiotics • The results of urine culture and sensitivity
appears to be as effective as a 7- to 14-day studies are usually available within 48 h.
course in children with lower UTIs. – If the pathogen is sensitive to the
– Guidelines from the American Academy of antibiotic used and the child is
Pediatrics recommend limiting fluoroqui- improving, continue treatment via
nolone therapy to patients with UTIs caused the parenteral route until the child
by Pseudomonas aeruginosa or other multi- has been afebrile for 24–36 h, has
drug-resistant, gram-negative bacteria. improved clinically, and is able to
Ciprofloxacin (Cipro) is used for compli- retain oral medications.
cated UTIs and pyelonephritis attributable – An oral antibiotic that is effective
to E. coli in patients 1–17 years of age. against the infecting organism may
– If the clinical response is not satisfactory then be substituted for parenteral
after 2–3 days, alter therapy on the basis of therapy.
antibiotic susceptibility – The hospitalized patient who is
– Symptomatic relief for dysuria consists of responding to treatment can go home
increasing fluid intake (to enhance urine after 48–72 h.
dilution and output), acetaminophen, and – Continue oral antibiotics for a total
nonsteroidal anti-inflammatory drugs of 10–14 days.
(NSAIDs) • Antibiotic prophylaxis is no longer recom-
– If voiding symptoms are severe and persis- mended for grades I through III VUR or pend-
tent, add phenazopyridine hydrochloride ing results of the renal and urinary bladder
(Pyridium) for a maximum of 48 h ultrasound.
• Children with Complicated Pyelonephritis: • Antibiotic prophylaxis is more often recom-
• Pyelonephritis is considered complicated mended for children with high-grade reflux
when it occurs in: (grade 3–5).
– A neonate or an infant • The current AAP guidelines do not recom-
– A patient with an anatomic abnormality of mend prophylactic antibiotics to prevent UTI
the urinary tract or abnormal renal recurrences.
function
– A patient who is immunocompromised Antibiotics used for parenteral treatment of a urinary
tract infection
• Start IV fluids, usually at 1–1.5 times
Drug Dose and route
the usual maintenance rate.
Ceftriaxone 50–75 mg/kg/day IV/IM as a single
• Parenteral treatment with a third- dose or divided q12 h
generation cephalosporin (e.g., ceftriax- Cefotaxime 150 mg/kg/day IV/IM divided
one, cefotaxime) is appropriate initial q6–8 h
empiric coverage for a complicated UTI Ampicillin 100 mg/kg/day IV/IM divided q8 h
and pyelonephritis to cover for Gentamicin *Term neonates <7 days: 3.5–5 mg/
ampicillin-resistant, gram-negative kg/dose IV q24 h
pathogens. *Infants and children <5 years:
2.5 mg/kg/dose IV q8 h or single
• Add ampicillin if gram-positive cocci
daily dosing with normal renal
are present in the urinary sediment or if function of 5–7.5 mg/kg/dose IV
no organisms are observed. q24 h
• Gentamicin is an alternative empiric *Children ≥5 year: 2–2.5 mg/kg/
choice and may be considered in patients dose IV q8 h or single daily dosing
with normal renal function of
with cephalosporin allergy. 5–7.5 mg/kg/dose IV q24 h
• Monitor renal function and blood ami- Ampicillin 200 mg/kg IV/day (divided every
noglycoside levels if gentamycin is 6 h)
required for more than 48 h. Tobramycin 5–7.5 mg/kg once per day
• Children with grade IV or V VUR or a signifi- vesicoureteral reflux and urinary antibiotic prophy-
laxis after acute pyelonephritis: a multicenter,
cantly abnormal renal and urinary bladder
randomized, controlled study. Pediatrics. 2006;117(3):
ultrasound should be evaluated further for a 626–32.
possible surgical management. 7. Girardet P, Frutiger P, Lang R. Urinary tract infections
• Constipation should be addressed in infants in pediatric practice. A comparative study of three
diagnostic tools: dip-slides, bacterioscopy and leuco-
and children who have had a UTI to help pre-
cyturia. Paediatrician. 1980;9(5–6):322–37.
vent subsequent infections. 8. Glissmeyer EW, Korgenski EK, Wilkes J, et al.
• There is some evidence that cranberry juice Dipstick screening for urinary tract infection in febrile
decreases symptomatic UTIs over 12-months, infants. Pediats. 2014;133(5):e1121–7.
9. Goldsmith BM, Campos JM. Comparison of urine
particularly in women with recurrent UTIs.
dipstick, microscopy, and culture for the detection of
• The effectiveness of cranberry juice in chil- bacteriuria in children. Clin Pediatr (Phila).
dren is less certain, and the high dropout rate 1990;29(4):214–8.
in studies indicates that cranberry juice may 10. Heldrich FJ, Barone MA, Spiegler E. UTI: diagnosis
and evaluation in symptomatic pediatric patients. Clin
not be acceptable for long-term prevention.
Pediatr (Phila). 2000;39(8):461–72.
11. Hoberman A, Charron M, Hickey RW, Baskin M,
Antibiotics used for prophylaxis Kearney DH, Wald ER. Imaging studies after a first
Antibiotic Single daily dose febrile urinary tract infection in young children. N
Sulfamethoxazole and 5–10 mg/kg SMZ, Engl J Med. 2003;348(3):195–202.
trimethoprim (SMZ-TMP) 1–2 mg/kg TMP 12. Hoberman A, Wald ER, Hickey RW, et al. Oral versus
PO initial intravenous therapy for urinary tract infections
Trimethoprim 1–2 mg/kg PO in young febrile children. Pediatrics. 1999;104(1 pt
1):79–86.
Nitrofurantoin 1–2 mg/kg PO
13. Hom J. Are oral antibiotics equivalent to intravenous
Cephalexin 10 mg/kg PO antibiotics for the initial management of pyeloneo-
phritis in children? Pediatr Child Health. 2010;15(3):
150–2.
14. Jepson RG, Williams G, Craig JC. Cranberries for
preventing urinary tract infections. Cochrane
Further Reading Database Syst Rev. 2012;(10):CD001321.
15. Keren R, Chan E. A meta-analysis of randomized,
1. [Guideline] Subcommittee on Urinary Tract Infection; controlled trials comparing short- and long-course
Steering Committee on Quality Improvement and antibiotic therapy for urinary tract infections in chil-
Management. Urinary tract infection: clinical practice dren. Pediatrics. 2002;109(5), E70.
guideline for the diagnosis and management of the 16. Lunn A, Holden S, Boswell T, Watson AR. Automated
initial UTI in febrile infants and children 2 to 24 microscopy, dipsticks and the diagnosis of urinary
months. Pediatrics. 2011. tract infection. Arch Dis Child. 2010;95(3):193–7.
2. American Academy of Pediatrics Task Force on 17. Michael M, Hodson EM, Craig JC, Martin S,
Circumcision. Circumcision policy statement. Moyer VA. Short versus standard duration oral
Pediatrics. 2012;130(3):585–6. antibiotic therapy for acute urinary tract infection
3. American Academy of Pediatrics, Subcommittee on in children. Cochrane Database Syst Rev.
Urinary Tract Infection, Steering Committee on 2003;(1):CD003966.
Quality Improvement and Management, Roberts 18. Montini G, Toffolo A, Zucchetta P, et al. Antibiotic
KB. Urinary tract infection: clinical practice guideline treatment for pyelonephritis in children: multicentre
for diagnosis and management of the initial UTI in randomised controlled non-inferiority trial. BMJ.
febrile infants and children 2 to 24 months. Pediatrics. 2007;335(7616):386.
2011;128(3):595–610. 19. Mori R, Lakhanpaul M, Verrier-Jones K. Diagnosis
4. Bloomfield P, Hodson EM, Craig JC. Antibiotics for and management of urinary tract infection in children:
acute pyelonephritis in children. Cochrane Database summary of NICE guidance. BMJ. 2007;335(7616):
Syst Rev. 2005;(1):CD003772. 395–7.
5. Finnell SM, Carroll AE, Downs SM. Technical 20. Pennesi M, Travan L, Peratoner L, Bordugo A,
report—diagnosis and management of an initial UTI Cattaneo A, Ronfani L, et al. Is antibiotic prophylaxis
in febrile infants and young children. Pediatrics. in children with vesicoureteral reflux effective in pre-
2011;128(3):e749–70. venting pyelonephritis and renal scars? A random-
6. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, ized, controlled trial. Pediatrics. 2008;121(6):
Campos A, Young L. Clinical significance of primary e1489–94.
Further Reading 335
21. Salo J, Ikäheimo R, Tapiainen T, Uhari M. Childhood 28. Tosif S, Baker A, Oakley E, Donath S, Babl
urinary tract infections as a cause of chronic kidney FE. Contamination rates of different urine collection
disease. Pediatrics. 2011;128(5):840–7. methods for the diagnosis of urinary tract infections in
22. Schoen EJ, Colby CJ, Ray GT. Newborn circumcision young children: an observational cohort study.
decreases incidence and costs of urinary tract infec- Paediatr Child Health. 2012;48(8):659–64.
tions during the first year of life. Pediatrics. 29. Tran D, Muchant DG, Aronoff SC. Short-course ver-
2000;105(4 Pt 1):789–93. sus conventional length antimicrobial therapy for
23. Schroeder AR, Chang PW, Shen MW, Biondi EA, uncomplicated lower urinary tract infections in chil-
Greenhow TL. Diagnostic accuracy of the urinalysis dren: a meta-analysis of 1279 patients. J Pediatr.
for urinary tract infection in infants <3 months of age. 2001;139(1):93–9.
Pediatrics. 2015;135(6):965–71. 30. Wald ER. Vesicoureteral reflux: the role of antibiotic
24. Shaikh N, Morone NE, Bost JE, Farrell MH. prophylaxis. Pediatrics. 2006;117(3):919–22.
Prevalence of urinary tract infection in childhood: a 31. Wan J, Skoog SJ, Hulbert WC, Casale AJ, Greenfield
meta-analysis. Pediatr Infect Dis J. 2008;27(4): SP, Cheng EY, et al. Section on Urology response to
302–8. new Guidelines for the diagnosis and management of
25. Singh-Grewal D, Macdessi J, Craig J. Circumcision UTI. Pediatrics. 2012;129(4):e1051–3.
for the prevention of urinary tract infection in boys. 32. Whiting P, Westwood M, Watt I, Cooper J, Kleijnen
Arch Dis Child. 2005;90(8):853–8. J. Rapid tests and urine sampling techniques for the
26. Supavekin S, Surapaitoolkorn W, Pravisithikul N, diagnosis of urinary tract infection (UTI) in children
Kutanavanishapong S, Chiewvit S. The role of DMSA under five years: a systematic review. BMC Pediatr.
renal scintigraphy in the first episode of urinary tract 2005;5(1):4.
infection in childhood. Ann Nucl Med. 2013;27(2): 33. Williams G, Craig JC. Long-term antibiotics for pre-
170–6. venting recurrent urinary tract infection in children.
27. Toffolo A, Ammenti A, Montini G. Long-term clinical Cochrane Database Syst Rev. 2011;(3):CD001534.
consequences of urinary tract infections during 34. Zorc JJ, Kiddoo DA, Shaw KN. Diagnosis and man-
childhood: a review. Acta Paediatr. 2012;101(10): agement of pediatric urinary tract infections. Clin
1018–31. Microbiol Rev. 2005;18(2):417–22.
Bladder Exstrophy-Epispadias
Complex 13
13.1 Introduction tract, genital tract, musculoskeletal system

and sometimes the intestinal tract.
• Bladder exstrophy (also known as Ectopia • The bladder exstrophy-epispadias complex
vesicae) is a congenital anomaly that exists as comprises a spectrum of congenital abnormal-
part of the exstrophy-epispadias complex. ities that includes (Figs. 13.1 and 13.2):
• It is characterized by protrusion of the open – Classic bladder exstrophy
urinary bladder through a defect in the lower – Epispadias
abdominal wall. – Cloacal exstrophy
• Bladder exstrophy-epispadias complex is a – Other rare variants
spectrum of rare congenital malformations – The spectrum often include abnormalities of
involving the urinary, genital, and musculo- the bony pelvis, pelvic floor, and genitalia
skeletal systems in which the bladder • The underlying embryologic mechanism lead-
remains open through a lower abdominal ing to this spectrum of anomalies is unknown
defect. but it is believed that all represent a spectrum
• Bladder exstrophy-epispadias-cloacal exstro- of the same embryological defect. It is thought
phy complex is the most severe and comprises to result from failed reinforcement of the cloa-
a spectrum of anomalies involving the urinary cal membrane by underlying mesoderm.
SMALL OMPHALOCELE
Fig. 13.1 A clinical ½ URINARY

photograph showing ½ URINARY
BLADDER
BLADDER
classic cloacal
exstrophy. Note the
open urinary bladder
into two halves and the
ileocecal region
protruding in the
middle of the bladder.
Note the small ILEOCECAL REGION
omphalocele

338 13 Bladder Exstrophy-Epispadias Complex

photograph showing
classic bladder
exstrophy. Note the
open urinary bladder.
Note also the associated OPEN URINARY
complete epispadias BLADDER
COMPLETE
EPISPADIAS
• The incidence: • Patients diagnosed intra-uterine with bladder

– The birth prevalence of classic bladder extrophy should be referred to specialized
exstrophy has been estimated to be between centers for further evaluation and
1 in 10,000 and 1 in 50,000 livebirths. management.
Others reported a prevalence of 3.3 per • Modern therapy is aimed at surgical recon-
100,000 births. struction of the bladder and genitalia.
– Males are affected two to three times more – Staged Repair of bladder Exstrophy:
often than females. • The initial step is closure of the abdomi-
– Isolated epispadias occurs in approxi- nal wall, often requiring a pelvic
mately 1 in 112,000 live male births and osteotomy.
1 in 400,000 live female births. • This leaves the patient with penile epi-
– The prevalence of Cloacal exstrophy is 1 in spadias and urinary incontinence.
200,000–400,000 births. • At approximately 6 months of age the
• The risk of bladder exstrophy in children born patient then undergoes repair of the epi-
to parents with bladder extrophy is approxi- spadias after testosterone stimulation.
mately 500-fold greater than the general • Finally, bladder neck repair usually is
population. done around the age of 4–5 years,
• The classic manifestation of bladder exstro- though this is dependent upon a bladder
phy is characterized by: with adequate capacity and, most impor-
– A defect in the abdominal wall occupied by tantly, an indication that the child is
both the exstrophied bladder as well as a interested in becoming continent.
portion of the urethra – Complete Primary Repair of bladder
– A flattened puborectal sling Exstrophy:
– Separation of the pubic symphysis • The bladder closure is combined with
– Shortening of the pubic ramii an epispadias repair.
– External rotation of the pelvis • Epispadias is a congenital malformation of
– Females also have: males in which the urethra opens on the upper
• A displaced and narrowed vaginal surface (dorsum) of the penis.
orifice • Epispadias is an uncommon congenital mal-
• A bifid clitoris formation of the penis and rarely occur as an
• Divergent labia isolated defect.
Figs. 13.3 and 13.4 Clinical photographs showing epispadias. In the first picture, the epispadias is limited to the glans
while in the second one there is complete epispadias
• It is seen more commonly as part of the – The urinary bladder mucosa is fully
epispadias-exstrophy complex. exposed through a triangular fascial defect
• It is now possible to diagnose exstrophy- on the lower abdomen.
epispadias complex antenatally using ultra- – The abdominal wall appears long because
sound and recently fetal magnetic resonance of a low-set umbilicus on the upper edge of
imaging. This is important to council the par- the urinary bladder plate.
ents and also to transfer these patients in-utero – The distance between the umbilicus and
to specialized centers with a team experienced anus is foreshortened.
in their management. The antenatal ultraso- – The rectus muscles diverge distally, attach-
nography findings suggestive of exstrophy- ing to the widely separated pubic bones.
epispadias complex include the following: – Inguinal hernias are frequently associated
– Failure to visualize the bladder with bladder extrophy.
– Lower abdominal wall mass • >80 % of males, and >10 % of females
– Low-set umbilical cord with bladder extrophy have inguinal
– Abnormal genitalia hernias.
– Increased pelvic diameter • This is due to wide inguinal rings and
– Omphalocele the lack of an oblique inguinal canal.
– Limb abnormalities – The phallus (Figs. 13.3, 13.4, and 13.5):
– Myelomeningocele • It is short and broad.
– Elephant Trunk sign from prolapsed • It is characterized by an upward curva-
intestine ture (dorsal chordee).
• Early attempts at bladder exstrophy repair were • The glans lies open and flat like a
unsuccessful and for many years the manage- spade.
ment for exstrophy consisted of excision of the • The dorsal component of the foreskin is
exstrophic bladder and urinary diversion com- absent.
monly by ureterosigmoidostomy. • The urethral plate is open and extends
• Anatomical defects in classic bladder exstrophy: the length of the phallus.
– The urinary bladder is open on the lower • The bladder plate and urethral plate are
abdomen in continuity, with the verumontanum
and ejaculatory ducts visible within the – The pubic symphysis is generally widened
prostatic urethral plate. but only mildly.
– The anus is anteriorly displaced with a nor- – The rectus muscles are divergent
mal sphincter mechanism. distally
• Anatomical defects in epispadias: – This can be an isolated anomaly or more
– The urethra opens on the upper surface commonly part of the extrophy-epispadias
(dorsum) of the penis. The extent of this is complex.
variable from only the glanular part to the • Anatomical defects in cloacal exstrophy
whole urethra. (Fig. 13.6):
– The bladder is open and separated into two
halves
– The exposed interior of the cecum is
within it.
– Openings to the remainder of the hindgut
and to one or two appendices are evident
within the cecal plate.
– The terminal ileum may prolapse as a
“trunk” of bowel onto the cecal plate.
– The phallus:
• The penis is generally quite small and
bifid
• A hemiglans is located just caudal to
each hemibladder.
• Infrequently, the phallus may be intact
in the midline.
• In females, the clitoris is bifid and two
vaginas are present.
Fig. 13.5 A clinical photograph showing epispadias as
– The anus is absent.
part of classic extrophy. Note the site of closure of bladder – Nearly all patients have an associated
extrophy omphalocele.
½ URINARY
BLADDER
OMPHALOCELE

photograph showing
cloacal extrophy. Note the ½ URINARY
BLADDER
urinary bladder divided
into two halves. Note the
ileocecal junction in the
middle between the two
halves of the bladder. Note ILEOCECAL
AREA
also the associated large
omphalocele
13.2 Embryology 341
– Musculoskeletal defects cloacal membrane results in formation of the

• The pubic symphysis is widely lower abdominal musculature and pelvic
separated. bones.
• The rectus muscles diverge distally but • After mesenchymal ingrowth occurs, down-
remain attached to the pubis. ward growth of the rectal septum divides the
• External rotation of the innominate cloaca into a bladder anteriorly and a rectum
bones results in a waddling gait but does posteriorly.
not appear to result in orthopedic prob- • The genital tubercles migrate medially and
lems later in life. fuse in the midline cephalad to the dorsal
– Neurologic defects membrane before it perforates.
• In cloacal exstrophy, as many as 95 % of • Failure of mesenchyme to migrate between
patients have myelodysplasia. the ectodermal and endodermal layers of the
• This may include myelomeningocele, lower abdominal wall leads to deficient lower
lipomeningocele, meningocele, or other abdominal wall and instability of the cloacal
forms of occult dysraphism. membrane.
• These patients are at risk of neurologic • The cloacal membrane is subject to premature
deterioration, and they should be rupture depending on the extent of the infra-
observed closely. umbilical defect.
• Anatomical defects in exstrophy variants: • Premature rupture of the cloacal membrane
– The pubic symphysis is widely separated before its caudal translocation leads to this
– The rectus muscles diverge distally. spectrum of anomalies.
– The umbilicus is low in position or • The timing and location of rupture of the cloa-
elongated. cal membrane dictate the patient’s presenta-
– A small superior bladder opening or a tion along the exstrophy-epispadias spectrum.
patch of isolated bladder mucosa may be • The stage of development when the membrane
present. rupture occurs determines whether bladder
– The intact bladder may be externally cov- exstrophy, cloacal exstrophy, or epispadias
ered by only a thin membrane. results.
– Isolated ectopic bowel segments have been • Epispadias occurs if the rupture produces a
reported. division or nonunion at the distal end of the
– Genitalia generally are intact, though epi- urinary tract.
spadias can occur. • The timing of the rupture of this cloacal defect
determines the severity of the disorder.
– Classic bladder exstrophy (60 %)
13.2 Embryology – Exstrophy variants (30 %)
– Cloacal exstrophy (10 %)
• The exact cause of these anomalies is not • Rupture of the cloacal membrane after com-
known but it is believed that all represent a plete separation of the genitourinary anteri-
spectrum of the same embryological defect. orly and the gastrointestinal tract posteriorly
• Embryoogically, the primitive cloaca is results in classic bladder exstrophy.
divided by the urorectal septum into the ante- • Rupture of the cloacal membrane prior to
rior urogenital sinus and posteriorly the descent of the urorectal septum and separation
hindgut. of the genitourinary and the gastrointestinal
• This occurs during the first trimester at tract leads to cloacal exstrophy.
approximately the same time as maturation of • Cloacal exstrophy must be distinguished from
the anterior abdominal wall. persistent cloaca or cloacal malformation.
• Mesodermal ingrowth between the ectoder- • This is the most extreme form of anorectal
mal and endodermal layers of the bilaminar malformation in female infants in which there
is incomplete separation of the urinary tract, meatus with mild pubic diastasis and a closed
genital tract and hindgut. anterior abdominal wall and bladder.
• The exact embryological defect is not known • Epispadias is a very rare congenital malforma-
and several theories have been proposed to tion of the male or female urethra, in which
explain this. the urethra opens dorsally.
• Marshall and Muecke theory is based on an • In females with epispadias, there is a fissure in
abnormal lower overdevelopment of the cloa- the upper wall of the urethra and out of the
cal membrane, which prevents the medial body through an opening above the clitoris or
migration of the mesenchymal tissue which it can present as a double clitoris.
impairs the proper development of the abdom- • In males with epispadias, the urethra opens on the
inal wall. superior surface of the penis. The extent of this
• Ambrose and O’Brian postulated that an opening is variable. It can involve only the glans
abnormal development of the genital hillocks or extend to involve the whole shaft of penis.
with fusion in the midline below rather than • This differentiates it from hypospadias which
above the cloacal membrane result in the is a congenital defect, in which the urethra
exstrophy defect. opens on the ventral surface of the penis.
• Another hypothesis describes an abnormal • Epispadias is very rare, with an estimated inci-
caudal insertion of the body stalk with failure dence of approximately 1 in 100,000 live male
of the interposition of the mesenchymal tissue births.
in the midline. As a consequence of this fail- • It is extremely rare in females.
ure, translocation of the cloaca into the depths • Complete epispadias is a rare congenital
of the abdominal cavity does not occur. A malformation.
cloacal membrane that remains in a superficial – It occurs in 1 in every 117,000 male births
infraumbilical position represents an unstable – It occurs in only 1 of every 484,000 female
embryonic state with a strong tendency to births
disintegrate. • Epispadias rarely occur as an isolated
defect.
• It is commonly seen as part of the exstrophy-
13.3 Epispadias epispadias complex.
• Diastasis of the pubic bone and external dis-
13.3.1 Introduction placement of the hips is seen in severe cases of
epispadias.
• Epispadias, bladder extrophy and cloacal • In males, epispadias is characterized by
extrophy are major embryological defects that (Figs. 13.7, 13.8, 13.9, and 13.10):
are known to be associated with long term – The urethra opens on the dorsum of the
morbidity. With the recent advances in surgical penis. This can affect only the glans or
techniques including bladder closure, pelvic extend to affect the whole urethra.
osteotomies, and traction and immobilization – The normal urethra is replaced by a broad
the majority of these patients can achieve full mucosal strip lying on the dorsum of the
continence, adequate sexual function, and corpora cavernosa.
improvement in quality of life. – A short phallus.
• In males, the external urethral opening (external – A penis that is typically broad.
meatus) is normally located at the tip of the penis. – Dorsal chordee (marked upward curvature
• In females, the external urethral opening is of the penis).
normally located between the clitoris and the • Patients with isolated epispadias have a low
vagina. incidence of associated abnormalities but
• Epispadias is the least severe form of Bladder those with the more severe form of exstrophy-
Exstrophy-Epispadias Complex and it is epispadias complex are at a slightly increased
characterized by a dorsally open urethral risk for associated malformations
13.3 Epispadias 343
Figs. 13.7, 13.8, and 13.9 Clinical photographs show- the whole urethra. Note the urethral opening on the dor-
ing epispadias. The first is a glanular type of epispadias sum of the penis
while the lower two show complete epispadias involving
– These patients are also at increased risk for

retrograde ejaculation when they reach
adolescence because of failure of bladder
neck to close completely.
13.3.2 Etiology
• The penis is formed by the corpus spongiosum

surrounding the urethra and by two corpora
Fig. 13.10 A clinical photograph showing epispadias. cavernosa.
Note the short phallus which is also broad. Note also the • These are composed of erectile tissue sur-
upward chordee of the penis and the urethral opening on rounded by the tunica albuginea (Buck fascia)
the dorsum of the penis
and the dartos fascia more superficially.
• Normally, the male urethra runs through the
penile shaft, ventrally to the corpora cavernosa,
• These include: and meets with the meatus at the tip of the
– Hydroureters glans.
– Hydronephrosis • The exact etiology of eispadias is not
– Vesicoureteral reflux. known.
• Epispadias and exstrophy of the bladder are – Glandular epispadias (Figs. 13.11, 13.12,
considered varying degrees of the same and 13.14):
disorder. • The extent of epispadias is limited to the
• Epispadias results from defective migration glans of the penis.
of the paired primordia of the genital • This is the rarest type.
tubercle. – Penile epispadias (Figs. 13.15 and 13.16):
• These fuse on the midline to form the genital • The epispadias opening extends along
tubercle at the fifth week of embryologic the whole shaft of the penis.
development. – Penopubic epispadias (complete):
• The epispadias opening extends to the
pubic bone.
13.3.3 Classification – Part of the exstrophy-epispadias complex
(Figs. 13.17 and 13.18).
• The extent of epispadias is variable. • Patients with glanular and about one-third of
• It can present as a small dimple on the tip of those penile epispadias usually have good
the glans penis just above the normal urethral
opening (Figs. 13.11 and 13.12).
• If the urethra and bladder are involved, the
epispadias is severe and this is part of the
spectrum of malformations called the
exstrophy-epispadias complex (Fig. 13.13).
• Commonly, the classification of epispadias is BLADDER
EXTROPHY
based on the location of the urethral meatus as
follows: COMPLETE
EPISPADIAS
Fig. 13.13 A clinical photograph showing complete epi-

spadias as part of the extrophy-epispadias complex. Note
the dorsal chordee
Figs. 13.11 and 13.12 Clinical photographs showing

glandular epispadias. Note the urethral opening on the Fig. 13.14 A clinical photograph showing glandular epi-
dorsum of the penis. It appear as a dimple on the dorsum spadias. Note the urethra opening on the dorsum of the
of the glans penis and limited to the glans of the penis
13.3 Epispadias 345
prognosis with normal urinary capacity and • These patients and those with exstrophy-
no urine incontinence. epispadias complex will require reconstruc-
• In most cases of penopubic epispadias, and tive bladder neck surgery to achieve urine
approximately two-thirds of those with penile continence.
epispadias have urine incontinence. • Currently, about 80 % of patients with
male epispadias patients are continent
postoperatively.
• The remaining patients who are still inconti-
nent may require later bladder neck
reconstruction.
• It is also estimated that about 87–100 % of iso-
lated female epispadias are continent
postoperatively.
13.3.4 Treatment
• The goals of treatment of epispadias are:

– To lengthen and straighten the penis by
correcting dorsal bend and chordee.
– To create a functionally and cosmetically
acceptable penis with an external urethral
meatus at the tip of the penis.
– To establish urinary continence and pre-
serve fertility in those with the more severe
forms.
• Patients with epispadias are born with a very
small or severely underdeveloped penis. These
Figs. 13.15 and 13.16 Clinical photographs showing patients are usually treated with long acting
penile epispadias. Note the dorsal chordee and the urethral
opening on the dorsum of the penis and extending along
testosterone preoperatively to enlarge the size
the shaft of the penis of the penis (Figs. 13.19, 13.20, and 13.21).
Figs. 13.17 and 13.18 Clinical photographs showing epispadias as part of the bladder extrophy. Note the scars after
closure of the urinary bladder
Figs. 13.19, 13.20, and 13.21 Clinical photographs showing epispadias before testosterone, after testosterone and at
the time of surgery. Note the increase in the size of the penis following testosterone injections
• They are given one or a maximum of three • There are three surgical techniques used to
doses at 3–4 weeks intervals (2 mg/kg/dose). correct epispadias:
Others use topical testosterone. – The Cantwell-Ransley procedure.
• The surgical treatment of epispadias differs – The Young procedure.
according to the complexity of the – The complete disassembly procedure.
malformation. • In this technique the two corpora caver-
• A staged approach has often been used for the nosa and a single corpus spongiosum
management of the exstrophy-epispadias are totally separated and the three com-
complex. ponents are reassembled and the urethra
• Currently, epispadias are treated with single constructed in such a way that the ure-
stage procedures. thra is in its normal position.
13.3 Epispadias 347
– A large number of children with the – Glanular and urethral reconstruction:

exstrophy-epispadias complex will subse- • The urethral meatus is correctly posi-
quently require bladder neck repair to tioned using a reversed meatal advance-
achieve continence. ment and glanuloplasty technique.
– Closure of penile skin
• The modern modified Cantwell-Ransley
13.3.5 Surgical Repair of Male repair is the most commonly used technique to
Epispadias (Figs. 13.22, 13.23, repair epispadias.
13.24, 13.25, 13.26, 13.27, • Mitchell and Bagli have described a further
13.28, 13.29, 13.30, 13.31, modification of Cantwell-Ransley repair
13.32, 13.33, 13.34, 13.35, “complete penile disassembly technique”.
and 13.36) – The urethral plate and each corporeal body
along with its hemiglans are dissected
• Intramuscular or topical testosterone is given completely free from each other.
preoperatively to increase the size of the – The urethra is then tubularized and placed
penis. into an anatomic, ventral position.
• The surgical repair of epispadias include: – This method of epispadias repair is often
– Correction of dorsal chordee: performed at the time of primary bladder
• This is achieved by mobilizing the ure- closure, the combination of which is called
thral plate from the underlying corpora “complete primary repair of bladder
from the level of glans down to the pros- exstrophy”.
tatic urethra. – This technique may be complicated by
• The corporal bodies are anastomosed at ischemia as a result damage to the blood
the dorsal medial aspect over the tubu- supply during dissection.
larized urethra. – The lateral dissection during this procedure
• Persistent chordee is corrected by can result in neurovascular bundle injury
cavernostomy. and consequent erectile dysfunction.
Figs. 13.22 and 13.23 Clinical photographs showing the broad penis. The length of the penis increased as a
epispadias being repaired. This was part of the exstrophy- result of testosterone injections
epispadias complex that was treated in two stages. Note
Figs. 13.24, 13.25, 13.26, and 13.27 Clinical operative photographs showing repair of glandular epispadias. Note
the good size and normal shape of the penis
– The tubularized urethra is usually shorter 13.3.6 Female Epispadias

than the actual corpora, resulting in hypo-
spadias which necessitate further • Female epispadias is extremely rare.
urethroplasty. • The reported incidence is approximately 1 of
• Postoperatively, the patients undergo yearly 500,000–600,000 live girls.
gravity cystograms to measure bladder capac- • Epispadias in females is commonly associated
ity. Bladder augmentation may be necessary with separated pubic bones.
for those with small bladder capacity. • Female epispadias is characterized by:
• Procedures to improve continence are usually – A bifid clitoris.
done at 5–9 years of age. – Diastases of the corpora cavernosa.
– The Young-Dees-Leadbetter bladder neck – Flattening of the mons.
reconstruction. – Separation of the labia.
– Bladder neck transection, bladder augmen- • The diagnosis of epispadias in females is always
tation, and continent urinary diversion can delayed as the defect may not be obvious.
be done simultaneously in those with small • The bladder neck is almost always involved in
bladder capacity. these patients leading to urinary incontinence.
13.3 Epispadias 349
Figs. 13.28, 13.29, and 13.30 Clinical operative photographs showing repair of epispadias after closure of bladder
extrohy. Note the scar of closure of the bladder extrophy and the normal size and shape of the penis
• Repair of female epispadias is much simpler • Like male epispadias patients, if the bladder
than male epispadias. template does not grow after bladder neck
• The two parts of the clitoris are sutured reconstruction, the patient may require blad-
together and the urethra is positioned in its der neck transection, bladder augmentation,
normal place. and continent urinary diversion.
• The prognosis of these patients is good and • Bilateral iliac osteotomies may be necessary
fertility is not affected. to correct the associated pubic diastasis.
13.3.7 Surgical Repair of Female 13.3.8 Prognosis

Epispadias
• The prognosis for male patients with
• Repair of isolated female epispadias is gener- epispadias depends on the extent of the
ally done along with Young-Dees-Leadbetter defect.
bladder neck reconstruction, monsplasty, and • Most patients with mild degrees of epispadias
clitoroplasty. do well.
Figs. 13.31, 13.32, and 13.33 Clinical operative photographs showing repair of epispadias. Note the normal size and
shape of the penis. Note also the good size and position of the urethral meatus
• They have penises that are normal in terms of • It is characterized by an abdominal wall
shape and function. defect, an open bladder and urethra with an
• They are continent and do not require further epispadias and a wide pubic diastasis.
surgeries. • The prevalence of classic bladder exstrophy is
• Their sexual function is normal and can have estimated to be 3.3 per 100,000 births.
children. • Classic bladder exstrophy is more common in
• Those with severe degrees of epispadias may males with a male-to-female ratio of 2.3:1 and
have erectile dysfunction are unable to as high as 6:1.
conceive children. • Bladder exstrophy can present as an isolated
• They may be incontinent and require surgeries classic bladder exstrophy or part of the cloacal
to correct this. exstrophy (Fig. 13.37, 13.38, 13.39, 13.40,
• The prognosis of females with epispadias is and 13.41).
usually excellent and their future fertility is • Bladder exstrophy is the most common pre-
not affected. sentation of exstrophy-epispadias complex,
occurring in approximately 1 per 10,000 to 1
per 50,000 births and affecting males approxi-
13.4 Bladder Exstrophy mately twice as often as females.
• The risk factors for bladder exstrophy include:
13.4.1 Introduction – Caucasian race
– Young maternal age
• Bladder extrophy is a rare congenital – Maternal multiparity
malformation. – Children conceived with in vitro fertilization
13.4 Bladder Exstrophy 351
Figs. 13.34, 13.35, and 13.36 Clinical photographs showing a redo repair of epispadias after initial failure of the
distal part of the repair
• Counseling should be provided to parents but,

due to a favorable outcome, termination of the
pregnancy is no longer recommended.
• Following reconstructive surgery of the blad-
BLADDER
EXSTROPHY der, continence rates of about 70–80 % are
expected during childhood.
• Additional surgery might be needed to
EPISPADIAS improve continence, bladder capacity and
emptying function.
• Urinary diversion should be considered only if
reconstructive surgery fails.
Fig. 13.37 A clinical photograph showing classic blad-
der extrophy. Note the open urinary bladder and the asso- • Psychosocial and psychosexual outcome is
ciated complete epispadias important in these patient and a multidisci-
plinary team approach is essential in this regard.
• If the patient’s bladder capacity does not
• The diagnosis of bladder extrophy epispadias increase sufficiently following closure, the
complex can be made prenatally by patient may ultimately need augmentation
ultrasound. cystoplasty.
– This is important to council parents • In cases when the bladder is excessively
– And also to transfer these patients prior to fibrotic or is too small even to attempt aug-
delivery to specialized centers experienced mentation, then bladder substitution surgery,
in the management of these patients. in the form of orthotopic neobladder or a

photograph showing
bladder exstrophy as part
of the cloacal exstrophy.
Note the urinary bladder
½ URINARY
divided into two parts and BLADDER ½ URINARY
the space between them is BLADDER
occupied by the prolapsed
ileocecal region. Note also
the associated anorectal
agenesis ILEOCECAL
REGION
ANORECTAL
AGENESIS
Figs. 13.39 and

13.40 Clinical ILEOCECAL REGION
photographs showing
bladder exstrophy as part
of the cloacal exstrophy.
Note the widely separated
two halves of the bladder. ½ URINARY ½ URINARY
Note also the prolapsing BLADDER BLADDER
ileocecal region between
the two halves of the
urinary bladder. Note also
the associated anorectal
agenesis and bilateral
club feet
½ URINARY
BLADDER
½ URINARY
BLADDER
ILEOCECAL REGION
continent catheterizable pouch, is generally – Achieving cosmetically and functionally

undertaken. acceptable external genitalia
• Reconstruction of exstrophy-epispadias com- – Creation of a neo-umbilicus
plex remains one of the greatest challenges • Repair of bladder exstrophy can be done in
facing the pediatric surgeons and pediatric one of two procedures:
urologist. – Staged functional closure for classic blad-
• The goals of treatment include: der exstrophy:
– Closing the defect in the urinary bladder • The bladder closure is completed within
– Closing the abdominal wall defect while 72 h of birth.
maintaining renal function • If this is delayed, pelvic osteotomies are
– Achieving urinary continence required to facilitate successful closure
– Maintaining sexual function of the abdominal wall and to allow the

photograph showing
ILEOCECAL REGION
bladder exstrophy as
part of the cloacal
exstrophy. Note the two
halves of the urinary 1/2 URINARY
bladder with stents in BLADDER
the two ureters 1/2 URINARY
BLADDER
bladder to lie within a closed and sup- – Indirect inguinal hernias are frequent
portive pelvic ring. (>80 % of males, >10 % of females) due to
• Epispadias repair with urethroplasty is wide inguinal rings and the lack of an
delayed till age 12–18 months. This oblique inguinal canal.
allows enough increase in bladder outlet – In males with classic bladder exstro-
resistance and improve the bladder phy (Figs. 13.42 , 13.43 , 13.44 , and
capacity. 13.45 ):
• Bladder neck reconstruction is done at • The phallus is short and broad with
age 4 years upward curvature (dorsal chordee).
• A modified Young-Dees-Leadbetter • The glans lies open and flat.
repair is preferred. Multiple modifica- • The dorsal component of the foreskin is
tions of this have been proposed. absent.
• This allows continence and correction • The urethral plate is open and extends
of vesicoureteral reflux. the length of the phallus.
– Complete primary repair for classic blad- • The bladder plate and urethral plate are
der exstrophy in continuity, with the verumontanum
• Primary bladder closure, urethroplasty, and ejaculatory ducts visible within the
and genital reconstruction are per- prostatic urethral plate.
formed in a single stage in newborns. • The anus is anteriorly displaced with a
• This procedure involves complete penile normal sphincter mechanism.
disassembly in males and mobilization – In females with classic bladder
of the urogenital complex in females. exstrophy:
• Hypospadias is a common outcome in • The clitoris is bifid with divergent labia
males and this requires subsequent superiorly.
urethroplasty. • The open urethral plate is in continuity
• Classic bladder exstrophy is characterized by: with the bladder plate.
– The bladder is open to the outside on the • The vagina is anteriorly displaced.
lower abdomen. The anus is anteriorly displaced with a
– The abdominal wall appears long because normal sphincter mechanism.
of a low-set umbilicus on the upper edge of • Radiological evaluation:
the bladder plate. – A baseline abdominal ultrasound is impor-
– The distance between the umbilicus and tant in these patients because increased
anus is foreshortened. bladder pressure after bladder closure can
– The pubic symphysis is widely separated. lead to hydronephrosis.
– The rectus muscles diverge distally, – Bilateral vesicoureteral reflux is common
attaching to the widely separated pubic and seen in nearly all patients with classic
bones. bladder exstrophy.
Figs. 13.42 and

13.43 Clinical
photographs of a male OPEN
with classic bladder URINARY
exstrophy. Note the BLADDER
small size of the open
urinary bladder and the
associated epispadias. EPISPADIAS
Note also the phallus
which is short, wide
with dorsal chordee
OPEN
URINARY
BLADDER
EPISPADIAS
BLADDER
EXTROPHY
BLADDER
EXTROPHY
VAGINAL
PROLAPSE
Fig. 13.44 A clinical photograph of a female with blad- Fig. 13.45 A clinical photograph showing bladder
der extrophy. Note the small size of the urinary bladder exstrophy in a female. Note also the associated vaginal
with granular appearance prolapse
13.4.2 Associated Anomalies • The ureters in bladder extrophy and cloacal

extrophy patients enter the bladder at an
• Associated anomalies are common in abnormal angle leading to vesicoureteral
patients with cloacal extrophy-epispadias reflux in all patients following bladder clo-
complex. sure. The ureters are most commonly
reimplanted into the bladder at the time of – These associated anomalies necessitate
augmentation or bladder neck reconstruc- prompt neurological evaluation with spinal
tion in staged repair. They can also be US and MRI and can further exacerbate
safely reimplanted during primary com- urinary and bowel incontinence, lower
plete repair. extremity immobility, and erectile
• Common urological anomalies include ure- dysfunction.
teropelvic junction obstruction, horseshoe
kidney, and ectopic kidney.
• The pelvic deformities may cause the child to 13.4.3 Principles of Surgical
ambulate with a waddling gait. Management of Bladder
• Magnetic resonance imaging (MRI) studies Exstrophy
have shown that the pelvic floor musculature
is also significantly different in patients with • The surgical technique of staged repair of
extrophy-epispadias complex. Cloacal extro- classic bladder exstrophy include:
phy patients have similar, but more severe, – Initial bladder closure is completed within
pelvic floor musculature abnormalities than 72 h of birth.
bladder extrophy patients. These deficits con- – If bladder closure is delayed, pelvic oste-
tribute to incontinence in these patients and otomies are required to facilitate successful
predispose females to vaginal and uterine closure of the abdominal wall and to allow
prolapse. the bladder to lie within a closed and sup-
• Gastrointestinal Abnormalities portive pelvic ring.
– An anteriorly displaced anus and anal – Performance of anterior innominate oste-
sphincter is found in patients with bladder otomy allows approximation of the pubic
extrophy. bones, closure of the symphysis pubis and
– Bladder extrophy patients occasionally abdominal wall muscles without tension.
have omphalocele, imperforate anus, rectal – This is performed in conjunction with pedi-
stenosis, and rectal prolapse. atric orthopedic surgeons.
– Cloacal extrophy patients almost always – The urinary bladder is drained via a supra-
have some gastrointestinal defect. These pubic tube or a urethral catheter and ure-
include omphalocele, imperforate anus, teral stents are also left in place.
rudimentary hindgut, malrotation of the – At the end of the first stage procedure, the
bowel, and short gut syndrome, the last of patient will be left with an epispadias.
which is often compounded by multiple – Repair of epispadias is delayed till the age
bowel surgeries. 12–18 months to allow time to improve
• Neurospinal Abnormalities bladder capacity.
– Approximately 7 % of bladder extrophy – The epispadias repair is performed using
patients will have a spinal abnormality the modified Cantwell-Ransley repair
such as spina bifida occulta, scoliosis, and technique.
hemivertebrae. – The bladder neck is reconstructed at the
– Spinal dysraphism may cause neurologic age of 4–8 years.
dysfunction. – Bladder neck reconstruction is done using
– Nearly all cloacal extrophy patients dem- the modified Young-Dees-Leadbetter
onstrate significant neurospinal deficits repair. This allows correction of associated
including: vesico-ureteral reflux.
• Neural tube defects – The procedure is delayed until bladder
• Vertebral anomalies capacity is adequate.
• Spinal myelodysplasia – It has been reported that the results are
• Spinal dysraphism much better with a bladder capacity greater
• Tethered cord than 85 ml.
centers and by experienced surgeons. The

reconstructive surgery consists of a series of
corrective surgeries performed over several
years.
• The management of these patients should be
in specialized centers and via a multidisci-
plinary approach which include:
– Neonatologist
– Pediatric gastroenterologist
– Pediatric urologist or pediatric surgeon with
special interest and expertise in the man-
agement of exstrophy-epispadias complex
– Neurosurgeon
– Pediatric Orthopedic surgeon
– Child psychiatrist
– Stoma therapist
– Social workers
Fig. 13.46 A clinical photograph showing the end result • The parents stress should not be overlooked
after staged repair of classic bladder exstrophy. Note the during the initial and long-term care of these
scar of bladder closure. Note also the small phallus with patients.
epispadias which needs to be repaired in the second stage
• A cardiac echo is commonly done to rule out
significant cardiopulmonary anomalies.
• The surgical technique of complete primary • A renal ultrasound should be obtained to eval-
repair for classic bladder exstrophy: uate the upper urinary tracts.
– In this technique, bladder closure, epispa- • A KUB is done to evaluate the pelvis bony
dias repair, and genital reconstruction are anatomy.
performed in a single stage in the newborn • A spinal ultrasound is done to rule out an asso-
period. ciated spinal dysraphism.
– Hypospadias is a common outcome in • Antibiotics should be started immediately
males postoperatively and requires subse- after delivery and continued postoperatively.
quent urethroplasty (Fig. 13.46). • Daily prophylactic antibiotic therapy should
be given to these patients during postoperative
follow-up.
13.4.4 Evaluation and Management • These patients have a high incidence of latex
sensitization and it is important to institute
• It is important to tie the umbilical cord imme- latex precautions.
diately after delivery with 2.0 silk as the • The goals of treatment include:
umbilical clamp causes irritation and trauma – Closing the defect in the urinary bladder
to the open urinary bladder. – Closing the abdominal wall defect while
• The bladder mucosa should be frequently irri- maintaining renal function
gated with warm saline and always covered – Achieving urinary continence and adequate
with a protective clear plastic wrap that is urinary storage at low pressures with the
changed at frequent intervals until the time of ability to empty the bladder completely
bladder closure. Avoid using wet gauze which without compromising renal function.
can cause irritation to the delicate bladder – Maintaining sexual function.
mucosa. – Achieving cosmetically and functionally
• The treatment of bladder exstrophy-epispadias acceptable external genitalia.
is complex should be performed in specialized – Creation of a neo-umbilicus
• In the past, early attempts at bladder exstrophy • Modified Buck’s traction exerts pull
repair were unsuccessful and for many years longitudinally on the lower extremities.
the management for bladder exstrophy con- • Modified Bryant’s traction, where the
sisted of excision of the exstrophic bladder hips are placed into 90° of flexion, may
and urinary diversion commonly by be used if there is no osteotomy.
ureterosigmoidostomy. • Spica casts to immobilize the pelvis
• The surgical management of bladder exstro- without the need for external fixators or
phy has changed over the years and many traction.
modifications in surgical techniques have • “Mummy wrapping” the child’s legs.
improved the outcome for these patients. • Complete Primary Repair of Exstrophy
• Currently, most patients are managed either (CPRE):
with: – This technique was pioneered by Dr.
– A (single stage) complete primary repair of Mitchell in 1996.
bladder exstrophy (Mitchell technique). – The CPRE is done as a one stage procedure
– Or modern staged reconstruction of with or without pelvic osteotomies and
exstrophy. includes:
• There are those who advocate a staged • Bladder closure with bladder neck
approach while others prefer total reconstruc- remodeling.
tion in one stage. • A disassembly technique for epispadias
• Early bladder closure (closure during the first repair.
72 h) is beneficial. • This technique allows for bladder
– It decreases inflammation and fibrosis of cycling and more ‘normal’ growth and
the bladder development because the bladder expe-
– Improves bladder growth and expansion riences an outlet resistance.
– Decreases the need for urinary diversion • The disassembly technique for epispa-
– Decreases the risk of precancerous changes dias repair also allows for division of
in the bladder the intersymphyseal ligaments and
• Pelvic osteotomies: appropriate anatomic placement of the
– Pelvic osteotomies may be performed at bladder neck and posterior urethra
the time of primary closure. deep into the pelvis in its normal
• This helps deepen the flattened pelvis position.
• Close the pubic diastasis • If the procedure is done within the first
• Release tension on the abdominal wall 72 h of life, the pelvis is malleable
– Pelvic osteotomies are recommended in enough to close without osteotomies.
patients who undergo repair after 72 h of age • Postoperatively, the patient is placed in
as this facilitates closure of the bladder and Bryant’s traction for approximately
abdominal wall and also results in deeper 1 week and then lower extremity casting
placement of the bladder into the pelvis. for 3 weeks to prevent tension on the
– A combination of bilateral anterior trans- pelvis closure.
verse innominate and vertical posterior • A large number of these patients require
iliac osteotomies has been shown to a formal bladder neck procedure to
decrease the rate of abdominal dehiscence achieve continence
and bladder prolapse. – Outcome and complications of CPRE:
– There are several maneuvers to facilitate • The outcome of CPRE is generally
this including: good.
• The use of fixator pins and external fixa- • Continence defined as dry intervals lon-
tion devices can be placed and left post- ger than 2 h and spontaneous voiding
operatively for 4–6 weeks. without catheterizations is around 75 %.
Figs. 13.47, 13.48, and 13.49 Clinical photographs showing repair of hypospadias following closure of classic blad-
der exstrophy and epispadias repair. Note the scar following closure of the urinary bladder
• About 30 % of these patients require • Modern Staged Reconstruction of Exstrophy

clean intermittent catheterization (CIC). (MSRE):
• There is a potential risk for renal dete- – In this technique, the exstrophic bladder is
rioration related to a high pressure lower closed first.
urinary system in these patients – A pelvic osteotomy will facilitate this clo-
• Glans necrosis and penile injury or sure as well as closure of the abdominal
loss. wall. This is especially so if the closure is
• Hydronephrosis, pyelonephritis and performed after 72 h of birth.
renal scarring. – The end result is a complete epispadias.
• Approximately 36–68 % of patients will – The epispadias repair is performed between
be left with a hypospadias that will 6 and 12 months of age.
require urethroplasty (Figs. 13.47, 13.48, – Penile growth can be stimulated with long
and 13.49). acting testosterone.
– The bladder neck repairs for continence is – Several techniques using segments of
performed between 4 and 5 years of age if bowel, stomach, or redundant ureter have
they have an adequate bladder capacity. been used to augment the bladder.
– This can be delayed until the bladder grows – Following augmentation cystoplasty, a
and maturity improves. continent urinary diversion is performed
– The other alternative is bladder augmenta- using a segment of appendix or ileum.
tion with a catheterizable channel and blad- – This segment connect the urinary bladder
der neck closure when necessary. to the abdominal wall and provide a conti-
– Outcome and complications: nent stoma through which to perform clean
• Continence rates are reported to be 70 % intermittent catheterization.
in males and 74 % in females with dry – This makes clean intermittent catheteriza-
periods greater than 3 h with spontane- tion much easier for these patients and
ous voiding and dry at night without more convenient.
clean intermittent catheterization. • In females, the external genitalia are fully
• A bladder capacity of 100 ml predicts reconstructed at the time of exstrophy
success at the time of bladder neck closure.
reconstruction utilizing the modified – This includes reapproximation of the bifid
Young-Dees-Leadbetter repair. clitoris and anterior labia to make a
• If the bladder capacity is less than fourchette.
100 ml, these patients should undergo – A monsplasty is an important part of
an augmentation at the time of recon- reconstruction in females using hair bear-
struction for continence. ing skin and fat to cover the midline
• Bladder neck reconstruction: defect.
– This allows continence and correction of – Further reconstruction is done during ado-
vesicoureteral reflux. lescent years including total urogenital
– The procedure is delayed until bladder mobilization to correct the location and
capacity is adequate; better results are angle of the vagina in female exstrophy
reported with a bladder capacity greater patients.
than 85 ml. – These patients usually have normal sexual
– A continence procedure such as the Young- desire and normal sexual intercourse after
Dees-Leadbetter, is delayed until the reconstruction.
patient achieves a bladder with adequate – These patients can subsequently become
capacity and desires continence (usually pregnant and deliver normally.
between 5 and 9 years of age). – There is however an increased risk of vagi-
– This stage is combined with ureteral reim- nal, cervical and uterine prolapse in these
plantation to repair associated vesicoure- patients. This is especially seen after preg-
teral reflux. nancy and delivery.
– Children who are not candidates for a con- – It is recommended that these patients
tinence procedure or who fail to achieve should undergo cesarean sections to elimi-
urinary continence after the procedure may nate stress on the pelvic floor and to avoid
require bladder neck transection, augmen- traumatic injury to the urinary sphincter
tation cystoplasty, and continent catheteriz- mechanism.
able stoma. • Male patients with exstrophy have normal
– This will make clean intermittent catheter- sexual function and libido but are at high risk
ization (CIC) to empty their bladders of infertility after reconstruction. These
easier. patients can be helped further with an assisted
• Bladder Augmentation: reproduction.
– This is indicated for patients with a bladder • Currently, 70–75 % of patients with bladder
that is noncompliant or of insufficient exstrophy are continent following modern
capacity. reconstruction.
• Postoperative complications include: • To include the components of cloacal exstro-

– Bladder Prolapse phy, it is also called the OEIS Complex:
– Bladder outlet Obstruction – O: Omphalocele
– Vaginal prolapse – E: Exstrophy of the cloaca
– Bladder Calculi – I: Imperforate Anus
– Renal Calculi – S: Spinal Defects
– Wound Dehiscence including urethra and • Clinically, patients with cloacal exstrophy
bladder dehiscence present at birth and the followings form the
– Hypospadias spectrum of anomalies that are related to cloa-
cal exstrophy (Figs. 13.51, 13.52, 13.53,
13.54, and 13.55):
13.5 Cloacal Exstrophy – Two exstrophied hemi bladders
– These are separated by a foreshortened
13.5.1 Introduction hindgut or cecum
– The hindgut is often blind-ending resulting
• Cloacal exstrophy is an extremely rare birth in an imperforate anus. This extrophied
defect with an estimated prevalence at ileo-cecal region presents between the two
around 1 in 50,000–200,000 live births hemi bladders (the “elephant trunk”
(Fig. 13.50). appearance).
• It is more common in males than females (a – Omphalocele
male-female sex ratio of 2:1). – Malrotation of bowel
• Cloacal exstrophy (EC) is a major birth defect – The symphysis pubis is widely separated
representing the severe end of the spectrum of – The pelvis is often asymmetrically
the exstrophy-epispadias complex. It is char- shaped
acterized by the presence of: – The genitalia (ambiguous genitalia):
– Omphalocele • The penile or clitoral halves are usually
– Bladder exstrophy located separately on either side of the
– Imperforate anus bladder plates with the adjacent scrotal
– Spinal defects or labial part.
• The size of omphalocele is variable. • Duplication of the vagina and uterus
• It is also called vesico intestinal fissure. • Vaginal agenesis
OMPHALOCELE
HEMIBLADDER
HEMIBLADDER
Fig. 13.50 Clinical ILEOCECAL REGION

photograph showing the
components of the cloacal
exstrophy
13.5 Cloacal Exstrophy 361
HEMIBLADDER
OMPHALOCEL
HEMIBLADDER
ILEOCECAL
REGION
OMPHALOCELE
HEMIBLADDER HEMIBLADDER
ILEOCECAL
REGION
OMPHALOCELE
HEMIBLADDER
ILEOCECAL
REGION
Figs. 13.51, 13.52, and 13.53 Clinical photographs showing two patients with cloacal exstrophy. Note the difference
in the size of omphalocele and also the extent of the exstrophied ileocecal region
NO OMPHALOCEL
ANORECTAL AGENESIS
ANORECTAL AGENESIS
Figs. 13.54, 13.55, and 13.56 Clinical photographs showing cloacal exstrophy in three patients. Note the absence of
omphalocele in the first one and associated anorectal agenesis in the other two patients
• Bladder Exstrophy-Epispadias Complex rep- • The bony pelvis is 14.7-degrees inferiorly

resents a spectrum of genitourinary malforma- rotated.
tions ranging in severity from epispadias and • The sacrum was 42.6 % larger by volume
classical bladder exstrophy to cloaca exstro- measurements and had 23.5 % more surface
phy. Add to this the exstrophy variants. Among area.
these, cloacal exstrophy is the most severe • These deformities of the pelvic bones contrib-
(Fig. 13.56). ute to the shortened phallus, waddling gait,
• Cloacal exstrophy is characterized by malfor- and outward rotation of the lower limbs in
mations of the gastrointestinal, musculoskele- exstrophy patients.
tal, and central nervous systems. Classically, a • Spina bifida occulta
portion of cecum or hindgut separates the two • Lumbarization or sacralization of vertebrae
open hemi bladders. • Uncomplicated scoliosis
• Three-dimensional CT is valuable to evaluate • Spinal dysraphism including myelomeningo-
the bony pelvis and pelvic floor in these cele, lipomeningocele, scimitar sacrum, and
patients. hemivertebrae.
• Antenatal imaging demonstrating absence of
bladder filling, a low-set umbilicus, widened
pubic rami, small genitalia, and a lower 13.5.3 Etiology and Pathogenesis
abdominal mass that increases throughout the
duration of pregnancy may indicate bladder • The exact etiology of cloacal exstrophy is not
exstrophy or cloacal exstrophy. known.
• The prolapsed ileum in cloacal exstrophy • Several theories have been proposed to
patients may look like an “elephant trunk explain the pathogenesis of cloacal exstro-
appearance” on antenatal ultrasound. phy but none of them can fully explain the
• Delivery of these patients should be arranged spectrum of anomalies seen in cloacal
at a specialized medical center with expertise exstrophy.
in managing this complex anomaly. Similarly, • The most accepted theory is that cloacal
infants who are diagnosed at birth should be exstrophy results from premature rupture of
promptly transported to such centers to allow the cloacal membrane prior to caudal migra-
for an experienced evaluation and possibly tion of the urorectal septum, and failure of
primary closure. fusion of the genital tubercles.
• Embryo logically:
– The urorectal septum divides the cloaca
13.5.2 Skeletal Changes in Cloacal into an anterior urogenital sinus and a pos-
Exstrophy terior anorectal canal.
– This occurs around the fourth week of
• Separation of the pubic bones intrauterine life and simultaneously, the
• Outward rotation of the innominate bones cloacal membrane is invaded by lateral
• Eversion of the pubic rami mesodermal folds.
• A 30 % shortage of bone in the pubic ramus – It is postulated that if this mesodermal
• External rotation of the posterior aspect of the invasion does not occur, the infraumbilical
pelvis cloacal membrane persists leading to poor
• Retroversion of the acetabulum lower abdominal wall development.
• External rotation of the anterior pelvis – The cloacal membrane eventually ruptures
• The sacro-iliac joint angle is 10-degrees larger but if this happens prior to the descent of
in the exstrophy pelvis compared to age- the urorectal septum which happens at
matched controls and 10-degrees more toward 6–8 weeks of gestation, then cloacal extro-
the coronal plane than sagittal. phy results.
– Cloacal extrophy develops as a result of: 13.5.5 Associated Anomalies

• Failure of the urorectal septum to
develop and divides the urogenital sinus • Cloacal exstrophy is commonly associated
anteriorly from the rectum posteriorly. with other anomalies including cardiovascu-
• Failure of the mesoderm forming the lar, and central nervous system anomalies.
infraumbilical abdominal wall to prolif- • Omphalocele (70–90 %)
erate and form the lower abdominal • Spinal and Skeletal Anomalies (46 %):
wall – The pelvic defects in cloacal exstrophy are
• Failure of the genital tubercle to develop. similar in nature but more severe than that
• Failure of these events to occur results in bladder exstrophy.
in exstrophy of both bladder and – The interpubic diastasis is wide.
intestine. – The anterior segment length (distance from
– Classically, cloacal exstrophy is made up the triradiate cartilage to the pubis) is
of omphalocele, exstrophied ileocecal shorter in cloacal exstrophy patients.
region of bowel, exstrophied hemi bladders – The angle of iliac wing is markedly
each with its ipsilateral ureter, and anorec- increased showing extreme external
tal agenesis. rotation.
– The pubic bones are widely separated, and – The ischiopubic angle is increased.
spinal dysraphism is common in these – Asymmetry between the pelvis sides, sac-
patients. roiliac joint malformations, and occasional
hip malformations
– Skeletal and limb anomalies were reported
13.5.4 Prenatal Diagnosis in 12–65 % of cases of cloacal exstrophy.
• Clubfoot deformities (Fig. 13.57)
• The prenatal diagnosis of cloacal exstrophy is • Absence of feet
now possible based on prenatal ultrasound • Severe tibial or fibular deformities
findings. • Congenital hip dislocations
• The prenatal ultrasound findings were classi- – Hemivertebra
fied into major and minor criteria. – Myelomeningocele
• The Major criteria include:
– Nonvisualization of the urinary bladder
(91 %)
– A large midline infraumbilical anterior
wall defect or a cystic anterior wall struc-
ture (82 %)
– An omphalocele (77 %)
– A myelomeningocele (68 %)
• The minor criteria include:
– Lower extremity anomalies (23 %)
– Renal anomalies (23 %)
– Ascites (41 %)
– Widened pubic arches (18 %)
– Narrow thorax (9 %)
– Hydrocephalus (9 %)
– A single umbilical artery (9 %)
– The characteristic elephant trunk appear-
ance that the prolapsing terminal ileum can Fig. 13.57 Clinical photograph of a newborn with cloa-
produce cal exstrophy. Note also the bilateral tallipes equinovarus
– Absence of feet • Neurospinal Anomalies:

– Sacralization of L5 – Neurospinal abnormalities have been noted
– Congenital scoliosis in 85–100 % of patients with cloacal
– Sacral agenesis exstrophy
– Interpedicular widening • Lumbar anomalies (80 %)
• Upper Urinary Tract Anomalies: • Thoracic anomalies (10 %)
– Upper tract anomalies are seen in 41–60 % • Sacral anomalies (10 %)
of patients with cloacal exstrophy. – Neurospinal anomalies include:
– These anomalies include: • Lipomeningoceles
• Ectopic Pelvic kidneys • Myelomeningoceles
• Horseshoe kidney • Spina bifida
• Renal agenesis • Isolated cord tethering
• Hydronephrosis and hydroureter – It is recommended that all cloacal exstro-
• Multicystic dysplastic kidneys phy patients have a spinal evaluation by
• Hypoplastic kidney or renal agenesis ultrasound or MRI. Ultrasound is quicker,
• Ectopic ureters easier, and less expensive and does not
• Ureteral duplication require sedation and the ultrasound find-
• Congenital stricture ings are comparable to MRI.
• Megaureters – The presence of a significant neurologic
• Solitary kidney deficit is associated with severe impair-
• Ureteropelvic junction obstruction ments and markedly decreased chance of
• Ureterocele developing continence.
• Lower extremity anomalies (30 %) – Long-term follow-up is important in these
• Double appendix (30 %) patients since up to 33 % can have symp-
• Absent appendix (21 %) tomatic spinal cord tethering.
• Short bowel syndrome (19–46 %) • Mullerian and Testicular Anomalies:
• Gastrointestinal duplications – The most common Mullerian anomaly
• Small bowel atresia (5 %) reported was uterine duplication (95 %).
• Abdominal wall musculature deficiency (1 %) The most common is partial duplication,
• Gastrointestinal Anomalies: predominately a bicornate uterus.
– Omphaloceles are reported in more than – Duplication of the vagina (65 %)
88–100 % of cloacal exstrophy and vary – Vaginal agenesis (25–50 %)
widely in size. – Undescended testes
– Other gastrointestinal anomalies were – Inguinal hernias
reported in 46 % of cloacal exstrophy patients. • Cardiovascular and Pulmonary Anomalies
• Malrotation – Life-threatening anomalies of the cardio-
• Bowel duplication vascular and pulmonary systems are rare.
• Duodenal atresia – There are rare reports of patients with cya-
• Duodenal web notic heart disease, aortic duplication, vena
• Meckel’s diverticulum caval duplication, bilobed lung and an
– Short gut syndrome is reported in 25 % of atretic upper lobe bronchus.
cloacal exstrophy patients.
– It is important to preserve as much bowel
as possible in these patients.
– Short gut syndrome can however develop
in the presence of normal small bowel
length suggesting an absorptive
dysfunction.
13.5.6 Clinical Features or no large bowel distally, but there are cases
and Management (Figs. 13.58, where there is colonic exstrophy with suffi-
13.59, and 13.60) cient large bowel length.
• A small colon usually ends blindly in the pel-
• Cloacal exstrophy is a very rare and complex vis, and the terminal ileum often prolapses out
anomaly of the urogenital tract and intestinal of the exposed cecum.
tract resulting in exstrophy of both bowel and • The presence of enough large bowel is advan-
bladder. tageous from the reconstruction point of view
• Commonly in cloacal exstrophy, the exstro- and every attempt should be made to preserve
phied bowel is the ileo-cecal region with little every part of bowel.
Figs. 13.58, 13.59, and 13.60 Clinical photograph divided into two halves and the prolapsed ileo-cecal
showing cloacal exstrophy. Note the omphalocele which region with the terminal ileum open with meconium pass-
is large in the first and small in the lower two pictures. ing from it. Note the large prolapsing ieocecal region in
Note also the urinary bladder in the first photograph the lower pictures
• The exstrophied ileocecal region and in the • The treatment of cloacal exstrophy is complex
presence of short large bowel should be pre- and should be performed in specialized cen-
served for reconstruction of the anorectal ters and by experienced surgeons.
malformation. • The reconstructive surgery consists of a series
• Every effort should be made to preserve all of corrective surgeries performed over several
large intestines because: years.
– It can be used for bladder augmentation • The management of newborns with cloacal
which is necessary in the majority of these exstrophy has progressed over the years, and
patients to increase the bladder now a very reasonable outcome is expected in
compliance. most cases. This, however, requires a team
– It can be used also for reconstruction of the approach including:
anorectal malformation. – Neonatologists
– It can be used for vaginal reconstruction in – Pediatric surgeons
those who have vaginal agenesis or those – Pediatric urologist
undergoing gender reassignment. – Neurosurgeons
• Add to this the valuable absorptive function of – Pediatric orthopedic surgeons
the large bowel. – Endocrinologist
• Augmentation of the urinary bladder may be – Geneticists
performed using the hindgut if enough length – Psychologist
is available, ileum, or part of the stomach. – Social workers
• In the absence of large intestine, both small – Stoma therapist
bowel and stomach can be used for bladder – Pediatric gastroenterologist
augmentation but gastrocytoplasty was shown • Although there are general guidelines in man-
to be superior. aging newborns with cloacal exstrophy, after
• Gender assignment is one of the difficult tasks thorough evaluation of the anatomical abnor-
in the management of newborns with cloacal malities, the management should be
exstrophy. individualized.
• It is important to determine early the genetic • Immediate management is directed to the
sex of the patient as this will affect the subse- medical stabilization of the infant.
quent management. • Evaluation and appropriate management of
• Genetic females should not raise a problem as associated malformations should be
they will be raised as females. undertaken.
• In genetic males with cloacal extrophy, the • For infants who have few other associated
phallic structures are usually small and com- malformations and are medically stable,
pletely bifid with insufficient phallic tissue to staged closure can be considered.
reconstruct an adequate penis. • The exposed bowel and urinary bladder should
• There is now general consensus that genetic be moistened with saline irrigation and cov-
males with insufficient phallus be gender reas- ered with protective plastic dressing. Wet
signed as phenotypic females, and to minimize gauze applied on the urinary bladder should
testosterone imprinting on the nervous sys- be avoided.
tem, this should be done in the immediate • Evaluation of the genitalia and gender assign-
newborn period with early orchidectomy. ment should be made by a gender assignment
• Males with adequate bilateral or unilateral team, including a pediatric urologist, pediatric
phallic structures should however, be raised as surgeon, pediatrician, and pediatric
males. endocrinologist.
• In the classic repair of cloacal extrophy in • Consultation of social worker, pediatric ortho-
males an epispadias is created initially after pedic surgeon and other disciplines should be
urinary bladder closure. obtained.
• These patients have a high incidence of latex

sensitization and it is important to institute
latex precautions.
• The initial operation consists of:
– Separating the bowel from the bladder to
create an intestinal stoma.
– Closing the omphalocele.
– Reapproximating, closing, or leaving the
exstrophied bladder undisturbed.
• The importance of creating a colostomy
instead of an ileostomy to prevent problems
with diarrhea, dehydration, and acidosis is to
be emphasized.
13.5.7 Surgical Repair of Cloacal

Exstrophy (Figs. 13.62, 13.63,
and 13.64)
• The surgical management of cloacal exstro-

phy includes:
– Pelvic osteotomy and immobilization
– Closure of urinary bladder
Fig. 13.61 A KUB of a patient with cloacal exstrophy. – Closure of abdominal wall
Note the soft tissue in mid lower part repressing the – An antireflux procedure
exstrophied bladder and ileocecal area. Note the widely – Augmentation cystoplasty
separated pelvis and pubic bones
– Continent urinary diversion
• After delivery, the exposed bladder and
• The parents stress should not be overlooked bowel mucosa should be covered or wrapped
during the initial and long-term care of to avoid mechanical irritation. The exposed
these patients. A detailed discussion with bladder is irrigated with warm normal
the parents is important. This should saline.
include gender assignment and manage- • A spinal ultrasound or MRI is important to
ment plan of these patients as well as future define and diagnose associated neurologic
prognosis. anomalies.
• A cardiac echo is done to rule out associated • A central line should be inserted as these
cardiopulmonary anomalies. patients require antibiotics and total parenteral
• A renal ultrasound should be obtained to eval- nutrition.
uate the upper urinary tracts. • Intestinal diversion is performed along with
• A KUB is done to evaluate the pelvis bony omphalocele repair.
anatomy (Fig. 13.61). • It is important to preserve any rudimentary
• A spinal ultrasound or MRI is done to rule out hindgut and part of bowel to avoid short bowel
an associated spinal dysraphism. syndrome.
• Antibiotics should be started immediately • The exposed urinary bladder is also closed.
after delivery and continued postoperatively. • Gender assignment is important for those
• Daily prophylactic antibiotic therapy should 46XY male cloacal exstrophy patients
be given to these patients during postoperative with inadequate phallic structures for
follow-up. reconstruction.
DIVIDED ILEUM
HEMIBLADDER
URETERIC
CATHETER
HEMIBLADDER
URETERIC
CATHETER
Fig. 13.62 A clinical intraoperative photograph of cloa- the divided ileum to form an ileostomy. Part of the bowel
cal extrophy being repaired. Note the two ureteric cathe- is left in the posterior wall of the urinary bladder for blad-
ters inserted and the mobilized urinary bladder. Note also der augmentation
ILEOSTOMY
URETERIC
CATHETER
Figs. 13.63 and

13.64 Clinical FOLEY’S CATHETER IN THE
intraoperative and ILEOSTOM BLADDER
post-operative photographs
showing a diverting
ileostomy and a urinary
catheter in the already
closed urinary bladder
• It is important to discuss the gender assign- – The appendix should be preserved for pos-
ment in these patients. sible later continent stoma construction if
– Many males with cloacal exstrophy have necessary.
an unreconstructable phallus and unde- – The hemi bladders are then re-approximated
scended testes. in the midline to create a single exstrophic
– The parents of these patients may elect to bladder (classic bladder exstrophy).
have their son undergo a gonadectomy and – If a one-stage is selected, the entire bladder
be raised as a female. is closed completely.
– This however may lead to possible psycho- – In patients with spinal dysraphism and
social and behavioral outcomes of geno- myelocystocele, a closure by a neurosur-
typic males being raised as females. geon is undertaken as soon as the infant is
– Currently, it is possible to reconstruct a medically stable.
functional and cosmetically acceptable • If reconstruction is to be done in one stage:
phallus and gender assignment should be – Complete penile disassembly and division
consistent with the karyotype. of the intersymphyseal band are crucial
– On the other hand and as a result of steps to allow for posterior positioning of
advancement of surgical techniques, many the bladder and urethra.
are advocating for assigning gender that is • Then reconstruction of the bladder, penis,
consistent with karyotype, phallus recon- abdomen, and pelvis approximates the normal
struction and orchidopexy. anatomy.
• Osteotomies are almost always necessary to
assist in closure and posterior placement of
13.5.8 Surgical Reconstruction the lower urinary tract. This allows a tension-
free approximation of the widely separated
• Cloacal exstrophy reconstructive procedures pubic bones and of the anterior abdominal
can be done as a one-stage or two-stage. wall. In cases of extreme pubic diastasis, com-
• A one-stage closure is preferable to minimize bined anterior innominate and posterior oste-
the number of neonatal procedures and allow otomy can be done or osteotomy is performed
the bladder to be closed and protected. along with external fixator placement for
• A central line should be inserted early for 2–3 weeks.
hydration, intravenous antibiotics and total • Postoperative drainage and immobilization
parenteral nutrition. are important via ureteral stents, a suprapubic
• Reconstruction consists of the followings: catheter and possibly a urethral catheter along
– Bilateral pelvic osteotomies are performed with traction and casting similar to that in
if reconstruction is done after the first 72 h classic bladder exstrophy.
of life. • In males with cloacal exstrophy, the penis is
– The omphalocele is excised. usually represented by two widely separated
– The bowel is separated from the hemi blad- small phallic structures. Reconstruction of
ders and care should be taken to preserve these is difficult and challenging.
the bowel length as much as possible to – Epispadias repair can be performed at the
avoid a short bowel. same time of initial closure when adequate
– The lateral vesicointestinal fissure is closed corporal tissue is present.
in continuity – Repair of epispadias can also be delayed.
– A short colostomy is created from the end of – In those with very small and insufficient
the distal colon segment and an ileostomy phallic tissue, a female sex rearing should
should be avoided as much as possible. be considered and discussed with the
family. This however should be considered 13.5.9 Management of Urinary

only in severe cases. Incontinence
– In females, the hemi clitoris are brought
together and duplicate vaginas are joined in • Incontinence of urine is common in patients
the midline if possible. with cloacal exstrophy.
– In the genotypic male patient raised as a • This may be due in part to spinal defects,
female, new vagina construction is usually which can cause a neurologic deficit in blad-
delayed till the time of puberty. der function, or to a small bladder capacity,
• Abdominal Wall and Bladder Closure which may require augmentation.
– Bilateral iliac osteotomies enable closure • Intermittent catheterization is important to
of the urinary bladder, abdominal wall and enhance bladder outlet resistance.
the widely separated pubic rami. • Urinary continence is possible in most chil-
– Urinary bladder closure, omphalocele clo- dren with cloacal exstrophy but usually will
sure and intestinal diversion are performed require a bladder augmentation and intermit-
with pelvic osteotomies within the first tent catheterization.
48–72 h of life. • Surgery to produce a continent reservoir
– A two-staged approach is indicated in those should be delayed until the child is old enough
with other associated anomalies, widely to participate in self-care.
separated pubic bones, a small bladder • The choice between a catheterizable ure-
template or if the patient is not medically thra or an abdominal stoma depends on the
fit. The omphalocele is repaired together adequacy of the urethra and bladder outlet,
with intestinal diversion. At about 6 months the intellect and dexterity of the child, and
later, the patient undergoes osteotomy and the child’s orthopedic status as regards to
then, bladder closure and genital revision. the spine, hip joints, braces and
• Postclosure Management: ambulation.
– The patients are kept immobilized postop- • Bladder augmentation should be delayed until
eratively for 4–6 weeks to allow the oste- bowel function is mature and nutrition and
otomies to heal. acidosis are no longer a problem.
– A modified Cantwell-Ransley repair of epi- • Bladder augmentation can be done using
spadias is planned at around 1 year of age. hindgut or ileum but to avoid further loss of
– Following epispadias repair, the patient’s bowel, part of the stomach can be used as a
bladder capacity is measured annually with gastrocystoplasty.
gravity cystogram. • There is a small risk of long-term cancer with
– The majority of cloacal exstrophy patients gastrocystoplasty.
require an augmentation cystoplasty and conti-
nent catheterizable stoma or a continent urinary
diversion. This is done at 6–8 years of age.
– During this procedure the patient will either 13.5.10 Prognosis
undergo a Young-Dees-Leadbetter bladder
neck reconstruction or bladder neck tran- • In bladder exstrophy and cloacal exstrophy,
section along with ureteral reimplantation the single most important predictor of long-
to prevent further vesicoureteral reflux. term bladder growth and continence is suc-
– Male patients, who continue to be raised as cessful primary bladder closure.
males, may require a phalloplasty or neo- • The postoperative continence in patients with
phallus if their original phallus is very bladder exstrophy and cloacal exstrophy
small. ranges from 70 % to 80 %.
13.5.11 Complications 2. Frimberger D. Diagnosis and management of epispa-

dias. Semin Pediatr Surg. 2011;20(2):85–90.
3. Gearhart JP, Jeffs RD. The use of parenteral testoster-
• The most common complications of both one therapy in genital reconstructive surgery. J Urol.
Cantwell-Ransley and complete penile disas- 1987;138(4):1077–8. Part 2.
sembly epispadias repair are persistent 4. Gearhart JP, Leonard MP, Burgers JK, Jeffs RD. The
Cantwell-Ransley technique for repair of epispadias.
chordee, urethrocutaneous fistula, and wound
J Urol. 1992;148(3):851–4.
dehiscence. 5. Gearhart JP, Mathews R. Penile reconstruction com-
• A complication specific to the Mitchell bined with bladder closure in the management of clas-
repair’s complete disassembly technique is sic bladder exstrophy: illustration of technique.
Urology. 2000;55(5):764–70.
glans and/or corporeal ischemia.
6. Gearhart JP, Mathews RI. Exstrophy-epispadias com-
• Complications following repair of bladder plex. In: Wein AJ, Kavoussi LR, Novick AC, Partin
exstrophy and cloacal exstrophy include: AW, Peters CA, editors. Campbell-walsh urology, vol.
– Wound dehiscence 4. 10th ed. Philadelphia: Elsevier; 2012. p. 3325–78.
7. Grady RW, Mitchell ME. Complete primary repair of
– Bladder prolapse
exstrophy. J Urol. 1999;162(4):1415–20.
– Bladder outlet obstruction 8. Grady RW, Mitchell ME. Management of epispadias.
– Vesicocutaneous fistula Urol Clin N Am. 2002;29(2):349–60.
• Complete primary repair of exstrophy may be 9. Mathews R. Achieving urinary continence in cloacal
exstrophy. Semin Pediatr Surg. 2011;20(2):126–9.
complicated by penile loss following penile
10. Mitchell ME. Bladder exstrophy repair: complete pri-
disassembly. mary repair of exstrophy. Urology. 2005;65(1):5–8.
• Intestinal complications following repair of 11. Mitchell ME, Bägli DJ. Complete penile disassembly
cloacal exstrophy include; for epispadias repair: the mitchell technique. J Urol.
1996;155(1):300–4.
– Ileus
12. Mushtaq I, Garriboli M, Smeulders N, et al. Primary
– Volvulus neonatal bladder exstrophy closure in neonates: chal-
– Small bowel obstruction lenging the traditions. J Urol. 2014;191(1):193–8.
• Augmentation cystoplasty and continent uri- 13. Oesterling JE, Jeffs RD. The importance of a success-
ful initial bladder closure in the surgical management
nary diversion may be complicated by:
of classical bladder exstrophy: analysis of 144 patients
– Bladder calculi treated at the Johns Hopkins hospital between 1975
– Chronic bacterial colonization and 1985. J Urol. 1987;137(2):258–62.
– Epithelial polyps 14. Schaeffer AJ, Stec AA, Purves JT, Cervellione RM,
Nelson CP, Gearhart JP. Complete primary repair of
– Mucus overproduction
bladder exstrophy: a single institution referral experi-
– Augmentation cystoplasty may be compli- ence. J Urol. 2011;186(3):1041–6.
cated by metabolic acidosis and carcinoma 15. Shnorhavorian M, Grady RW, Andersen A, Joyner
– The creation of stoma may be complicated BD, Mitchell ME. Long-term follow-up of complete
primary repair of exstrophy: the seattle experience.
by stenosis, prolapse, ischemia, and leakage
J Urol. 2008;180(4, supplement):1615–20.
16. Suson KD, Preece J, Baradaran N, Di Carlo HN,
Gearhart JP. The fate of the complete female epispa-
Further Reading dias and female exstrophy bladder—is there a differ-
ence? J Urol. 2013;190(4):1583–9.
17. Zaontz MR, Steckler RE, Shortliffe LMD, Kogan BA,
1. Baird AD, Gearhart JP, Mathews RI. Applications of
Baskin L, Tekgul S. Multicenter experience with the
the modified Cantwell-Ransley epispadias repair in the
Mitchell technique for epispadias repair. J Urol.
exstrophy-epispadias complex. J Pediatr Urol.
1998;160(1):172–6.
2005;1(5):331–6.
Megacystis Microcolon Intestinal
Hypoperistalsis Syndrome (Berdon 14
Syndrome)
14.1 Introduction – Hydronephrosis

– Dilated small bowel
• Berdon syndrome, also called Megacystis- – The pathological findings consist of an
microcolon-intestinal hypoperistalsis syndrome abundance of ganglion cells in both dilated
(MMIH syndrome), is an autosomal recessive and narrow areas of the intestine.
fatal genetic disorder affecting newborns. • MMIHS carries a poor prognosis and most of
• It is a familial disturbance of unknown the cases die within the early months of their
etiology. lives, nevertheless there are some case reports
• It was first described by Walter Berdon et al. recently of long-term survival.
in 1976. • These cases mostly die from malnutrition,
• They described the condition in five female sepsis, kidney failure, and liver failure depend-
infants, two of whom were sisters. All had ing on TPN and the complications of TPN.
marked dilatation of the bladder and some had • In 2011 and in an extensive review of 227 chil-
hydronephrosis and the external appearance dren with the MMIHS, Gosemann and Puri
of prune belly. The infants also had microco- reported a 19.7 % survival rate and the oldest
lon and dilated small intestines (Fig. 14.1). reported survivor was 24 years old. The vast
• Megacystis microcolon intestinal hypoperi- majority of the surviving patients had to be
stalsis syndrome (MMIHS) is the most severe maintained by total or partial parenteral
form of functional intestinal obstruction in the nutrition (TPN). The main causes of death
newborn. were sepsis, malnutrition and multiple organ
• The etiology of MMIHS is unknown. failure.
• Megacystis Microcolon Intestinal • Prenatal diagnosis of MMIHS is possible by
Hypoperistalsis Syndrom (MMIHS) is found in antenatal ultrasound and an antenatal ultra-
females three or four times more than in males. sound finding of an enlarged urinary bladder
• It is characterized by (Figs. 14.2, 14.3, 14.4, and intraabdominal mass in a female fetus
14.5, and 14.6): should alert the treating physicians for
– A dilated, giant non obstructed urinary MMIHS.
bladder (megacystis) • The usual presentation of newborns with
– Urinary retention MMIHS is abdominal distension. This is
– Microcolon caused by a markedly distended, but non-
– Hypoperistalsis or absent peristalsis of the obstructed urinary bladder. This usually fills
gastrointestinal tract leading to functional the whole abdomen and may reach to the
intestinal obstruction. xiphisternum.

374 14 Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (Berdon Syndrome)

a markedly enlarged
urinary bladder. Note also DILATED
STOMACH
the dilated stomach. There
was no evidence of
vesicoureteral reflux
DILATED
URINARY
BLADDER
DILATED URINARY
BLADDER
Fig. 14.4 An intraoperative clinical photograph showing

a markedly dilated urinary balder. Note the thick wall of
the enlarged urinary bladder
14.2 Etiology
• MMIHS is a rare congenital anomaly inher-

ited as an autosomal recessive and predomi-
nantly affects females (4:1 ratio).
• There are however reports of sporadic cases.
Figs. 14.2 and 14.3 Abdominal CT-scans showing a • MMIHS is inherited as an autosomal recessive
markedly dilated urinary bladder. Note also the associated with the gene locus at 15q11.
bilateral hydronephrosis • The exact etiology of MMIHS is not known.
• There are several theories to explain its patho-
• Treatment is supportive and involves an ileos- genesis but the most commonly accepted eti-
tomy to defunction the colon, with TPN. ology is that MMIHS is a form of visceral
• Multiorgan transplantation is suggested as a myopathy.
valuable alternative for children with severe • This was supported by histological studies
gastrointestinal dismotility. which showed smooth muscle myopathy as
14.2 Etiology 375
Figs. 14.5 and 14.6 Lower contrast enema showing small unused microcolon
the most predominant intestinal manifesta- • Several subsequent reports have confirmed
tion. This affects both the circular and longitu- evidence of intestinal myopathy in MMIHS.
dinal layers of the small bowel muscularis • MMIHS has been reported with excessive
propria. smooth muscle glycogen storage postulating
• Histological studies of the myenteric and sub- the pathogenesis involving a defect of
mucosal plexuses of the bowel of MMIHS glycogen-energy utilization.
patients have found normal ganglion cells in • Other investigators have reported absence or
the majority of the patients, decreased in some, marked reduction in smooth muscle actin and
hyperganglionosis and giant ganglia in others. other contractile and cytoskeletal proteins in
• An imbalance in intestinal peptides was sug- the smooth muscle layers of bowel in MMIHS
gested as one of the possible causes of • Molecular analysis have linked the disease to the
hypoperistalsis. neuronal nicotinic acetylcholine receptor
• Absence of Interstitial Cell of Cajal (ηAChR), namely the absence of a functional α3
(Pacemaker cells) in the bowel and urinary subunit of the ηAChR, a de novo deletion of the
bladder has been reported as a causative proximal long arm of chromosome 15 (15q11.2).
factor. • Immunohistochemical staining for smooth
• Puri and coworkers showed vacuolar degen- muscle actin, however, was selectively absent
erative changes in the smooth muscle cells in the circular layer, demonstrating isolated
with abundant connective tissue between mus- absence in a unique and previously unde-
cle cells in the bowel and bladder. scribed pattern. These observations raise the
possibility that the proximal long arm of chro-

mosome 15 (15q11) may be of clinical signifi-
cance in MMIHS.
• Histological evaluation of biopsies showed
DILATED URINARY
normal or excessive amounts of ganglion cells BLADDER
both in the dilated and collapsed parts of intes-
tines. In some reports, the ganglion were pres-
ent but described as mostly immature.
• In addition, there was vacuolization and
Fig. 14.7 A clinical intraoperative photograph showing a
degeneration in bladder and intestinal smooth
markedly dilated urinary bladder
muscles.
– A dilated non-obstructed urinary bladder.

14.3 Clinical Features This is associated with bilateral hydroure-
ters and hydronephrosis.
• Polyhydramnios is present in about 25 % of – Microcolon.
MMIHS cases. – Dilated stomach and proximal small bowel
• The main manifestation of MMIHS is abdom- (Figs. 14.8, 14.9, and 14.10).
inal distension secondary to the dilated non- – Dilated esophagus.
obstructed urinary bladder (Fig. 14.7). • Other reported associated anomalies include:
• Usually, infants present with bilious vomiting – Intestinal malrotation
and abdominal distension caused by func- – Short bowel
tional intestinal obstruction and bladder – Segmental stenosis of small intestine
distension. – Bilateral streak gonad
• Failure to pass meconium and features of – Bilateral duplicated urinary system
intestinal obstruction. – Omphalocele
• MMIHS is characterized by the presence of: – Meconium ileus (Figs. 14.11 and 14.12)
– A markedly distended urinary bladder
without distal urinary tract obstruction.
This is palpable clinically and if a urinary 14.5 Diagnosis
catheter is passed, a large amount of urine
will be drained and the size of the distended • Prenatal diagnosis of MMIHS is possible by
urinary bladder will decrease. It is impor- antenatal ultrasound.
tant not to empty the distended urinary • This usually shows an intra-abdominal mass
bladder rapidly. representing the enlarged urinary bladder and
– Small unused microcolon. There is failure bilateral hydroureters and hydronephrosis.
to pass meconium and a naso-gastric tube • Plain abdominal x-ray will show a dilated
will drain bile stained fluid due to upper stomach with little gas distally (Fig. 14.13).
intestinal obstruction. • The diagnosis of MMIHS is confirmed by
– Decreased or absent intestinal peristalsis. demonstrating a dilated non-obstructed uri-
nary bladder and a small unused microcolon.
• This can be demonstrated by an abdominal
14.4 Associated Anomalies ultrasound, abdominal CT-scan, a micturating
cystourethrogram and a contrast enema
• Megacystis Microcolon Intestinal (Fig. 14.14).
Hypoperistalsis Syndrome is characterized • The dilated stomach and esophagus can be
by: outlined by an upper contrast study.
14.6 Treatment and Prognosis – Malnutrition

– Sepsis
• The management of MMIHS is supportive as – Renal failure
there is no definite cure. – Liver failure
• The majority of patients with MMIHS die • Treatment is supportive and involves:
within the first year of life. These patients – A central line should be inserted for long
mostly die from: term total parenteral nutrition.
– An ileostomy to decompress the small
intestine (Figs. 14.15 and 14.16).
– A urinary catheter or a vesicostomy to
drain the dilated urinary bladder.
• A vesicostomy to decompress the distended
DILATED
STOMACH urinary bladder is a better alternative for long-
term drainage of the urinary bladder.
• MMIHS is known to have a high mortality but
there are however reports of long term
survivors.
• The survival in MMIHS in recent years has
improved. The majority of survivors are either
maintained by TPN or have undergone multi-
Fig. 14.8 Intraoperative photograph showing a markedly organ transplantations.
dilated stomach with a nasogastric tube in a patient with
MMIHS
Figs. 14.9 and 14.10 Barium swallow and meal showing markedly dilated esophagus, stomach and upper part of the
small intestines in a newborn with MMIHS
Figs. 14.11 and 14.12 Intraoperative photographs showing dilated stomach and small intestines filled with inspis-
sated meconium (meconium ileus) in a patients with MMIHS
Fig. 14.14 Abdominal CT-scan with oral contrast show-

ing a markedly dilated stomach. Note also the dilated uri-
nary bladder
• Several attempts at multi-organ transplanta-

tion or combined liver and intestinal trans-
plant in infants with MMIHS have been
reported to be successful.
• Currently, multivisceral transplantation is the
only accepted treatment modality for these
patients.
Fig. 14.13 Abdominal X-ray showing dilated stomach
with little air distally
Further Reading 379
Figs. 14.15 and 14.16 Clinical photographs showing the two stomas (ileostomies) in patients with MMIHS. The
proximal stoma never functioned. Note also the central line inserted for total parenteral nutrition
syndrome and bilateral streak gonads. Indian

Further Reading J Nephrol. 2011;21(3):212–4.
4. Masetti M, Rodríguez MM, Thompson JF, et al.
1. Gosemann JH, Puri P. Megacystis microcolon intesti- Multivisceral transplantation for megacystis microco-
nal hypoperistalsis syndrome: systematic review of lon intestinal hypoperistalsis syndrome.
outcome. Pediatr Surg Int. 2011;27(10):1041–6. Transplantation. 1999;68(2):228–32.
2. Loinaz C, Rodríguez MM, Kato T, et al. Intestinal and 5. Puri P, Shinkai M. Megacystis microcolon intestinal
multivisceral transplantation in children with severe hypoperistalsis syndrome. Semin Pediatr Surg.
gastrointestinal dysmotility. J Pediatr Surg. 2005;14(1):58–63.
2005;40(10):1598–604. 6. Steiner SJ, Steven J. Megacystis-microcolon-
3. Mantan M, Singhal KK, Sethi GR, Aggarwal intestinal hypoperistalsis syndrome (MMIHS).
SK. Megacystis, microcolon, intestinal hypoperistalsis J Pediatr Gastroenterol Nutr. 2004;39(3):301.
Cloacal Anomalies
15
15.1 Introduction • The goals of treatment include an anatomic

reconstruction with the aim of achieving:
• In animal anatomy, a cloaca/kloʊˈeɪkə/kloh- – Urinary control
ay-kə (plural cloacae /kloʊˈeɪsiː/kloh-ay-see) – Bowel control
is the posterior orifice that serves as the only – Sexual function
opening for the digestive, reproductive, and • Persistent cloacae occur exclusively in girls
urinary tracts of certain animals. and is considered the most complex and tech-
• All amphibians, birds, reptiles, and a few nically challenging defect in the spectrum of
mammals have this orifice, from which they anorectal malformations.
excrete both urine and feces. • The etiology of persistent cloaca is unknown.
• This is in contrast to most placental mammals, • A common error in the diagnosis of cloaca
which have two or three separate orifices for may occur during the neonatal period where
evacuation. physician may confuse it with high anorectal
• The word cloaca comes from Latin, and means malformation with a rectovaginal fistula.
sewer derived from cluō, which meant • The cooperation of a pediatric surgeon and
“cleanse”. pediatric urologist is important in this regard.
• A persistent cloaca is a complex congenital • Cloacae represent a spectrum of defects, but
birth defect in which there is a confluence of the common denominator is the presence of a
the rectum, vagina, and urethra into a single single perineal orifice and the rectum, vagina,
common channel (Figs. 15.1 and 15.2). and urethra open into a single common
• The exact incidence of cloacal anomalies is channel.
unknown but it is estimated to occur in 1 per • The length of this common channel is variable
20,000–25,000 live births. and ranges from 1 to 10 cm, with an average
• Cloacal anomalies occur exclusively in girls. length of approximately 3 cm.
• They comprise the most complex defect in the • The length of this common channel is impor-
spectrum of anorectal malformations. tant both surgically and also for prognosis.
• The management of these patient is chal- • More than 80 % of all patients with a cloaca
lenging and these patients should be man- have an associated urogenital anomaly.
aged in specialized centers with surgeons • All patients must be evaluated at birth for an
experienced in the management of these associated urologic malformation.
patients.

382 15 Cloacal Anomalies
Fig. 15.1 A diagrammatic

representation of cloaca. RECTUM
Not the urethra, vagina and
rectum opening in a
common channel. The BLADDER
length of the common
channel is important for
prognosis
VAGINA
COMMON
visualization and repair of the voluntary mus-

cles of urinary and fecal continence.
• It is important to accurately diagnose persistent
cloaca in the neonatal period because 90 % of
these patients have an associated urologic prob-
lem, and 40 % of them may present also with an
abdominal mass secondary to hydrocolpos.
• The hydrocolpos may produce two important
complications:
– It may compress the trigone of the urinary
bladder, producing ureterovesical obstruc-
tion, megaureter, and hydronephrosis.
– The vagina may become obstructed leading
to accumulation of the cervical glands
Fig. 15.2 A clinical photograph of a patient with cloaca.
Note the common single perineal opening. No separate
secretion. This leads to the formation of
urethral or anal openings seen hydrocolpos.
– Hydrocolpos if left undrained may become
infected, leading to a pyocolpos.
• The goals of treatment include an anatomic • Approximately 40 % of patients with cloaca
reconstruction to achieve bowel and urinary have a double Mullerian system consisting of
control, as well as normal sexual function. two hemiuteri and two hemivaginas.
• In 1982, Pena introduced the posterior sagittal • This septation disorder may be partial or total
approach to repair high anorectal malforma- and symmetric or asymmetric.
tion. This technique was also used to repair • It is important to recognize and document this
cloacal malformations. for future follow-up of these patients.
• This technique is extended and used to repair • The urinary tract and the distended vagina
the more complex cloacae and it is called the (Hydrocolpos) may both need to be managed
posterior sagittal anorectovaginourethroplasty within the newborn period to avoid serious
(PSARVUP). complications. Drainage of the distended
• This approach allowed for direct exposure to vagina may lead to resolution of the secondary
the complex anatomy and an excellent urological complications.
• The goals of management of cloaca include: – Add to this the less-developed sacra, asso-
– Early and accurate diagnosis of both cloaca ciated spinal problems, and less-developed
and associated anomalies. perineal musculature.
– Immediate neonatal management including – The input of a neurosurgeon in this is
fecal, urinary and vaginal diversion important as release of a tethered cord may
depending on the presentation. improve the functional outcome especially
– An anatomic reconstruction to achieve the urodynamics.
bowel and urinary control, as well as nor- – Anomalies of the sacrum, particularly
mal sexual function. hypodevelopment, sacral hemivertebrae,
• Currently, the posterior sagittal anorectovagi- and hemisacra, are associated with tethered
nourethroplasty (PSARVUP) is the preferable cord and most likely comprise the spectrum
approach to treat cloacal malformations. This of caudal regression, of which spinal
approach is important for direct exposure to anomalies are a part.
the complex anatomy and also allows excel- • Patients with anorectal malformations and
lent visualization of the voluntary muscles of tethered cord have a worse functional progno-
urinary and fecal continence. sis regarding bowel and urinary function.
• Sacrum and spine anomalies:
– The sacrum is the most frequently affected
15.2 Associated Anomalies bony structure.
– Associated anomalies of the sacrum
• Associated anomalies are common in patients include hemisacrum, hypodevelopment of
with cloaca. the sacrum and sacral hemivertebrae.
• More than 80 % of all patients with a cloaca – The degree of sacral deficiency is assessed
have an associated urogenital anomaly. by calculating the sacral ratio.
• These include: – The sacrum is measured, and its length is
– Absent kidney compared with bony parameters of the pel-
– Vesicoureteral reflux vis on an anteroposterior and a lateral
– Horseshoe kidney radiographs.
– Ectopic ureters – Calculation of sacral ratio:
– Double ureters • The distance from the coccyx to the sac-
– Hydronephrosis, and megaureters as a roiliac joint divided by the distance
result of vesicoureteral reflux or uretero- from the sacroiliac joint to the top of the
vesical obstruction. pelvis.
• Tethered cord: – The assessment of the hypodevelopment of
– Tethered cord has a known association with the sacrum correlates with the patient’s
anorectal malformations and is particularly functional prognosis.
common in patients with persistent cloaca. – Normal sacra have a ratio of greater than
– A tethered spinal cord refers to an intraver- 0.7.
tebral fixation of the phylum terminale. – Bowel control has rarely been observed in
– This may result in motor and sensory dis- patients with ratios less than 0.3.
turbances of the lower extremities. – A hemisacrum is almost always associated
– Spinal ultrasonography in the first 3 months with a presacral mass, commonly a presa-
of life and MRI thereafter are useful in cral teratoma, or an anterior meningocele.
diagnosis of tethered cord and associated – This may be part of the Currarino triad,
spinal and sacral anomalies. which includes:
– Patients with tethered cord have a worse • An anorectal malformation
functional prognosis regarding bowel and • A hemisacrum
urinary function. • A presacral mass
– Hemivertebrae may also affect the lumbar 15.4 Clinical Features

and thoracic spine, leading to scoliosis.
– Patients with cloaca may also have spinal • Persistent cloaca is a clinical diagnosis that is
anomalies other than tethered cord, such as usually made in the neonatal period.
syringomyelia and myelomeningocele. • The diagnosis of persistent cloaca is made
• Genital anomalies: clinically (Fig. 15.5).
• Approximately 50 % of patients have various • Normally, there are three perineal openings, a
degrees of vaginal or uterine septation. urethral opening, a vaginal opening and an
– Absent vagina anal opening.
– 2 hemivagina • The presence of only two openings (a urethra
– 2 hemiuteri and vaginal openings) suggests an anorectal
malformation.
• The presence of a single perineal orifice is
15.3 Classification diagnostic clinically of a persistent cloaca.
• The presence of abdominal distension with a
• Cloacae represent a wide spectrum of palpable abdominal mass is most likely
anomalies. secondary to a distended vagina (hydrocolpos)
• In all, the rectum, vagina and urethra open (Figs. 15.6 and 15.7).
together in a common channel. • A hydrocolpos is present in 40 % of patients
• The length of this common channel is variable with persistent cloaca.
and ranges from 1 to 10 cm with an average of – The distended vagina is a common cause of
3 cm. an obstructed urinary tract because of its
• The length of this common channel is impor- pressure on the trigone.
tant both for management and prognosis. – These patients may initially have hydrone-
• Based on the length of the common channel phrosis and hydroureter and once the
cloacae are divided into two main groups: vagina is decompressed, the urinary tract
1. Short common channel: The length of the may no longer be obstructed.
common channel is less than 3 cm – If the hydrocolpos is not drained during the
(Figs. 15.3 and 15.4) newborn period, it can become infected
2. Long common channel: The length of the (pyocolpos) and can lead to sepsis and vag-
common channel is more than 3 cm inal scarring.
(Fig. 15.4).
LONG
SHORT COMMON
COMMON CHANNEL
CHANNEL
Figs. 15.3 and 15.4 Diagrammatic representation of based on the length of the common channel. It is a short
cloaca. Note the length of the common channel which is common channel if the length of the common channel is
variable ranging from 1 to 10 cm but commonly around less than 3 cm and log common channel if it is more than
3 cm. The cloaca is divided into two types, low and high 3 cm
• The external genitalia in these patients are uterus may spill over to the peritoneal cavity
usually not well developed and often appear via the Fallopian tubes leading to ascites.
small. • The distended vagina is also a common cause
• Some of these patients may present with of an obstructed urinary tract because of its
abdominal distension and examination of the pressure on the trigone of the urinary
abdomen may reveal an abdominal mass, bladder.
which likely represents a distended vagina • This leads to obstruction of the uretro-vesical
(hydrocolpos) and is present in about 40 % of junction leading to hydroureter and
patients with persistent cloaca. hydronephrosis.
• The distended vagina may also lead to disten- • A severe hydronephrosis may lead to calcy-
sion of the uterus leading to hydrometrocol- eal rupture with urine extravasation either
pos and sometimes the fluids distending the retroperitoneally or in the peritoneal
cavity.
• It is important to decompress the distended
vagina as soon as possible and once the vagina
is decompressed, the urinary tract may no lon-
ger be obstructed and usually the hydroureter
END COLOSTOMY
and hydronephrois resolve.
• If the hydrocolpos is not drained during the
newborn period, it can become infected
leading to pyocolpos. This is a serious condi-
tion which may lead to septicemia.
• A hemisacrum in these patients is almost
always associated with a presacral mass, com-
monly teratomas, or anterior meningoceles.
A SINGLE PERNEAL
OPENING • The Currarino triad includes:
– An anorectal malformation
– A hemisacrum
Fig. 15.5 A clinical photograph showing a not well
– A presacral mass (teratoma, anterior
developed external genitalia in a patient with cloaca. Not
also the colostomy which was done in the newborn period. meningocele)
Note also the presence of a single perineal opening
Figs. 15.6 and 15.7 Clinical photographs of a newborn with cloaca showing abdominal distension secondary to
hydrocolpos
15.5 Investigations – The Currarino triad, which includes an

anorectal malformation, a hemisacrum,
• Plain radiography of the spine: and a presacral mass should be excluded.
– This is to look for spinal anomalies, such as • Abdominal ultrasonography is useful to evalu-
spina bifida and spinal hemivertebrae. ate intraabdominal organs including the
• Plain radiography of the sacrum: vagina and uterus as well as the presence or
– This is to look for sacral anomalies, such as absence of hydrocolpos.
a hemisacrum and sacral hemivertebrae. • Spinal ultrasonography is also used in infants
– The degree of sacral hypodevelopment can less than 3 month to evaluate for tethered cord.
also be assessed. • Echocardiography to detect associated cardiac
– Traditionally, to evaluate the degree of anomalies.
sacral hypodevelopment, the number of • A distal loopogram in those with a prelimi-
sacral vertebral bodies was counted. nary colostomy. The position of the rectum
– A more objective assessment of the sacrum must be carefully checked to determine
can be obtained by calculating the sacral ratio. whether it can be comfortably reached from a
– To calculate the sacral ratio (Fig. 15.8): posterior sagittal incision (Fig. 15.9).
• The distance from the coccyx to the sac- • Prior to definitive repair of cloacal malforma-
roiliac joint is measured and divided by tions, it is important to determine the length of
the distance from the sacroiliac joint to the common channel and the length of the ure-
the top of the pelvis. thra from the common channel to the bladder
• To calculate the sacral ratio, a lateral neck.
radiography is more accurate than the • This is determined using cystoscopy with vag-
anteroposterior view. inoscopy and a three-dimensional (3D) cloa-
• The sacral ratio is important as this cor- cagram under anesthesia. This is also valuable
relates with the patient’s functional in studying the genital anatomy (vaginal sep-
prognosis. tum, numbers and patency of cervices, and
• The normal sacral ratio is greater than 0.7. size and height of the vagina) (Fig. 15.10).
• Bowel control has rarely been observed • A cloacagram is performed by injecting a
in patients with ratios less than 0.3. water soluble contrast into the single perineal
– A hemisacrum is almost always associated orifice and taking radiographs that will show
with a presacral mass, commonly a tera- the bladder, vagina and rectum and their
toma, or an anterior meningoceles. anatomic relation. Cross-lateral radiographs
are more informative as well as the length of
the common channel.
• MRI is currently the procedure of choice to
evaluate the anomalies of the cloaca, the pres-
ence of tethered cord, sacrum and spine. MRI
is used in infants older than 3 months
(Fig. 15.11).
• Cystoscopy and vaginoscopy are essential
components for evaluation of the patient with
persistent cloaca. These are usually performed
before the main repair to define the anatomy
and plan the surgical repair. The following
anatomic points are checked:
NORMAL RATIO = BC ÷ AB = 0.74 – The length of the common channel
– The presence of a vagina
Fig. 15.8 Diagrammatic representation of calculating the – The presence of hemivagina
sacral ratio
15.6 Management 387
Fig. 15.9 A contrast study

showing the urinary
bladder and rectum in a
patient with cloaca
URINARY RECTUM
BLADDER
– To drain associated hydrocolpos

– To divert the urinary tract when necessary
– To achieve bowel control, urinary control,
and normal sexual function.
• Total diversion of the fecal stream is made
with an end colostomy placed in the descend-
ing colon and with a mucous fistula.
• This total diversion of the fecal stream is
important to prevent urinary infections.
• It is important to leave an adequate bowel
length distal to the site of the colostomy for
subsequent pull-through.
• The definitive procedure to repair cloaca is
posterior sagittal anorectovaginourethroplasty.
• This procedure simultaneously repairs the
rectal, vaginal, and urethral anomalies.
• The more complex anomalies are repaired
using a combined abdominal approach and
posterior sagittal anorectovaginourethroplasty.
• The repair of persistent cloaca represents a
Fig. 15.10 A contrast study through the perineal opening technical challenge and should be per-
showing the vagina, the urethral opening and rectum
formed in specialized centers by pediatric
surgeons dedicated to the care of these
– The presence of a cervix (or cervices) patients.
– The visualization of the rectal fistula • The management of cloaca is performed in
stages.
– The first stage is in the newborn period and
15.6 Management (Figs. 15.12, consists of fecal diversion and urinary and
15.13, 15.14, 15.15, and 15.16) vaginal diversion if necessary.
– The definitive repair of cloaca is performed
• The goals of early management of cloaca are: at a later date. This is done using the poste-
– To detect associated anomalies. rior sagittal anorectovaginourethroplasty
– To achieve satisfactory diversion of the (PSARVUP). Complex cases will require
gastrointestinal tract. laparotomy also. This depends on the
Fig. 15.11 MRI of a

patient with cloaca
showing the rectum,
urethra and vagina joining
distally together in a
common channel
RECTUM
VAGINA
URINARY
BLADDER
• For patients with a common channel longer

UTERUS
than 3 cm, a laparotomy is usually required.
FALLOPIAN – The vagina and urinary tract are separated
TUBE
to gain length
VAGINA
– The urethra is then reconstructed.
– Complex vaginal mobilizations are often
URINARY required, and vaginal replacement (with
BLADDER
colon or small intestine) is frequently
necessary
Fig. 15.12 An intraoperative photograph of a patient
with cloaca who presented with hydrometrocolpos. Note • Posterior sagittal anorectovaginourethroplasty
the distended vagina and uterus (PSARVUP) consists mainly of:
– Separating the rectum from the urogenital
tract.
length of the common channel which var- – Followed by separation of the vagina from
ies from 1 to 10 cm. the urethra and bladder.
– This is followed by colostomy closure. – Reconstruction of the common channel as
• The goals of surgical treatment are to achieve a neo-urethra.
bowel control, urinary control, and normal – Mobilization and dissection of the vagina
sexual function. This depends on: so that it could be pulled down to be placed
– The quality of the sacrum and spine posterior to the urethra wall.
– The quality of the sphincter muscles – Performance of a pull-through of the rec-
– The length of the common channel tum. The pull-through rectum is placed
• If the common channel is shorter than 3 cm, within the limits of the sphincter mecha-
the posterior sagittal approach can be used to nism, which is determined with an electri-
repair the defect without an abdominal cal stimulator.
approach. • The repair can usually be performed using
– The rectum is mobilized first and the vagina only the posterior sagittal approach.
and urethra are then mobilized together • For more complex anomalies, an abdominal
(total urogenital mobilization). approach is added to mobilize a very high
– Total urogenital mobilization allows mobi- vagina or gain length on a very high rectum.
lization of the urethra and vagina as one • If the common channel is shorter than 3 cm,
structure. the posterior sagittal approach can be used to
15.6 Management 389
Figs. 15.13 and 15.14 Intraoperative photographs of a patient with cloaca showing the already opened vagina which
was distended secondary to hydrocolpos
Figs. 15.15 and 15.16 Intraoperative photograph showing dilated sigmoid colon in two patients with cloaca
repair the defect without an abdominal • The pulled-through rectum is placed within
approach. the limits of the sphincter mechanism, which
• For patients with a common channel longer is determined with an electrical stimulator.
than 3 cm, a laparotomy is usually required. • Total diversion of the gastrointestinal tract is
• Complex vaginal mobilizations are often achieved with a colostomy (a double barrel
required, and vaginal replacement (with colostomy) placed in the descending colon.
colon or small intestine) is frequently This leaves a sufficient length of the colon for
necessary. subsequent pullthrough.
• Total urogenital mobilization is a technique • Total diversion of the fecal stream is necessary
that allows mobilization of the urethra and to avoid spillage and prevent urinary tract
vagina as one structure. infections.
• If total urogenital mobilization does not ade- • The patient must be left with a good length of
quately lengthen the vagina, the vagina and distal colon long, enough for the future pull-
urethra must be separated, which is a techni- through, and sometimes for a vaginal replace-
cally challenging procedure. ment if needed.
• The mucous fistula is also important for radio- length of the common channel, the presence
logic evaluation of the distal colon. of vagina or a bifid vagina, the presence of one
• A Foley catheter is placed in the bladder and cervix or more and the site of rectal fistula.
this remains in place for approximately This is valuable and help the surgeon to pre-
10–14 days. For more complex cases, a dict whether a laparotomy will be required in
vesicostomy or suprapubic cystostomy tube combination with the posterior sagittal
may be needed for longer-term urinary approach.
diversion. • Prognostic factors include:
• Anal calibration is performed 2 weeks after – The quality of the sacrum and spine.
the operation, followed by a program of anal – The quality of the sphincter muscles.
dilatations. – The length of the common channel.
• Once the desired size is reached, the colos- • Approximately 50 % of patients have various
tomy can be closed. degrees of vaginal or uterine septation. These
• Cystoscopy and vaginoscopy should be per- can be totally or partially repaired during the
formed before colostomy closure to ensure main operation.
that no urethrovaginal fistula is present. • The Foley catheter remains in place for
• A urethrovaginal fistula if present will need to approximately 10–14 days.
be closed prior to colostomy closure. • Anal calibration is performed 2 weeks after
• Patients with cloaca have no contraindications the operation, followed by a program of anal
to definitive surgery when future fecal or uri- dilatations. Once the desired size is reached,
nary incontinence is a concern. the colostomy can be closed.
• Even for patients with incontinence, a bowel • Cystoscopy and vaginoscopy should be per-
management program is almost always suc- formed before colostomy closure to ensure
cessful in keeping a patient clean and dry. that no urethrovaginal fistula is present, which
• In patients in whom bowel management is would necessitate a reoperation which should
unsuccessful (<3 %), a permanent colostomy be done with the colostomy still in place.
may be the best option to ensure good quality • Dilatations are continued afterward according
of life. to a prescribed protocol. They are a vital part
• In patients with urinary incontinence, many of the postoperative management to avoid a
options are available for keeping a patient stricture at the anoplasty site.
clean. • Many of these patients require a bowel man-
• Urinary diversions, such as the Mitrofanoff agement program to keep them clean and dry.
procedure and the use of intermittent catheter- • In patients in whom bowel management is
ization, are usually successful in keeping the unsuccessful (<3 %), a colostomy may be the
patient dry of urine. best option to ensure good quality of life.
• The repair of persistent cloaca represents a • In patients with urinary incontinence, many
technical challenge and should be performed options are available for keeping a patient
in specialized centers by pediatric surgeons clean.
dedicated to the care of these patients. This • Urinary diversions, such as the Mitrofanoff
especially for cloaca with a long common procedure and the use of intermittent catheter-
channel. ization, are usually successful in keeping the
• A distal colostogrphy through the mucous fis- patient dry of urine.
tula is essential to outline the anatomy. • Many of these patients require prophylactic
• Cystoscopy and vaginoscopy are essential antibiotics for urinary tract infections for
components for better evaluation of the patient associated vesicoureteral reflux.
with persistent cloaca. This is important to • Intermittent catheterization is required in 70 %
define the anatomy and plan surgical recon- of patients with persistent cloaca who have a
struction. It is important to determine the common channel longer than 3 cm, compared
Further Reading 391
with 20 % in those with a common channel 6. Hendren WH. Management of cloacal malformations.
Semin Pediatr Surg. 1997;6(4):217–27.
shorter than 3 cm.
7. Hendren WH. Cloaca, the most severe degree of
• In most patients, the bladderneck is compe- imperforate anus: experience with 195 cases. Ann
tent, and the patients who require catheteriza- Surg. 1998;228(3):331–46.
tion remain dry between voids. If 8. Levitt MA, Bischoff A, Peña A. Pitfalls and chal-
lenges of cloaca repair; how to reduce the need for
catheterization is not performed, overflow
reoperations. J Pediatr Surg. 2011;46:1250–5.
incontinence occurs. 9. Levitt MA, Mak GA, Falcone RA, Peña A. Cloacal
• In those with non-competent bladderneck or exstrophy – pull through or permanent stoma? A
nonexisting bladder neck, urinary diversion, review of 53 patients. J Pediatr Surg.
2008;43:164–70.
such as a Mitrofanoff procedure, with bladder
10. Levitt MA, Peña A. Cloacal malformations: lessons
neck tightening may be needed. learned from 490 cases. Semin Pediatr Surg.
2010;19:128–38.
11. Lund DP, Hendren WH. Cloacal exstrophy: a 25-year
experience with 50 cases. J Pediatr Surg.
2001;36(1):68–75.
Further Reading 12. Patel MN, Racadio JM, Levitt MA, Bischoff A,
Racadio JM, Peña A. Complex cloacal malforma-
1. Bischoff A, Levitt MA, Breech L, Louden E, Peña tions: use of rotational fluoroscopy and 3D recon-
A. Hydrocolpos in cloacal malformations. J Pediatr struction in diagnosis and surgical planning. Pediatr
Surg. 2010;45:1241–5. Radiol. 2012;42:355–63.
2. Bischoff A, Levitt MA, Lim FY, Guimarães C, Peña 13. Peña A. The surgical management of persistent clo-
A. Prenatal diagnosis of cloacal malformations. aca: results in 54 patients treated with a posterior sag-
Pediatr Surg Int. 2010;26:1071–5. ittal approach. J Pediatr Surg. 1989;24:590–8.
3. Hendren WH. Further experience in reconstructive 14. Pena A. Total urogenital mobilization – an easier way
surgery for cloacal anomalies. J Pediatr Surg. to repair cloacas. J Pediatr Surg. 1997;32(2):263–7;
1982;17(6):695–717. discussion 267–8.
4. Hendren WH. Urological aspects of cloacal malfor- 15. Soffer SZ, Rosen NG, Hong AR, Alexianu M, Pena
mations. J Urol. 1988;140(5 Pt 2):1207–13. A. Cloacal exstrophy: a unified management plan.
5. Hendren WH. Cloacal malformations: experience J Pediatr Surg. 2000;35(6):932–7.
with 105 cases. J Pediatr Surg. 1992;27(7):890–901.
Urachal Remnants
16
16.1 Introduction • The urachus is also known to undergo malig-

nant transformation and adenocarcinoma is
• The urachus is a fibrous remnant of the the commonest.
allantois. • A rare urachal tumor has been reported as a
• The allantois is a canal that drains the urinary manifestation of IgG4-related disease.
bladder of the fetus and runs within the umbil-
ical cord.
• The urachus is a band of fibrous tissue extend- 16.2 Embryology
ing from the dome of the bladder to the umbil-
ical cord. • Embryologically, the amniotic cavity bulges
• By 32 weeks, the urachus is obliterated and over the embryo and attaches to the yolk sac
becomes a vestigial structure known as the and the connecting stalk to form the umbilical
median umbilical ligament (not to be confused cord.
with the medial umbilical ligament, which is a • Further caudal folding of the embryo incorpo-
separate structure that lies laterally to the rates the proximal yolk sac into the hindgut
median umbilical ligament). and the allantois which is a diverticulum of the
• The urachus remnant lies in the space of yolk sac into the urogenital sinus.
Retzius, between the transversalis fascia ante- • The yolk and body stalks fuse to become the
riorly and the peritoneum posteriorly. umbilical cord.
• In 0.1–2.0 % of the population, the urachus • In the third week of gestation, the allantois,
remains patent and may result in urine leaking which grows into the body stalk is formed as a
from the umbilicus or infected urachal cysts. diverticulum from the yolk sac.
• Persistence of urachal remnant can give rise to • The allantois appears on about day 16 as a
various clinical problems: tiny, finger-like outpouching from the caudal
– Urachal cyst wall of the yolk sac.
– Urachal fistula • The bladder develops from the ventral portion
– Urachal diverticulum (Vesicourachal of the expanded terminal part of the hindgut,
diverticulum) the cloaca, which is contiguous with the allan-
– Urachal sinus tois ventrally.
• Because urachal remnants are uncommon and • The cranioventral end of the bladder opens
manifest with nonspecific abdominal or uri- into the allantois at the level of the umbilicus;
nary signs and symptoms, definitive presurgi- thus, the bladder initially extends all the way
cal diagnosis is not easily made. to the umbilicus.

394 16 Urachal Remnants
• By the fourth or fifth month of gestation, the remains narrow and is usually obliterated by
bladder descends into the pelvis and its apical fibrous proliferation.
portion progressively narrows to a small, epi- • In one-third of adults, it may be visible at
thelialized fibromuscular strand, the urachus microscopic examination as a structure
(Figs. 16.1, 16.2, and 16.3). communicating with the lumen of the blad-
• In late embryonic and fetal life and early post- der; however, in terms of function it can be
natal life, the urachal portion, which is still considered closed by the latter half of fetal
microscopic, fails to grow; thus, its lumen life.
CONNECTING STALK
AMNION
ALLANTOSIS
YOLK SAC ALANTOTIC BLOOD VESSELS
OMPHALOMESENTERIC DUCT
ALLANTOSIS
GI TRACT
UMBILICAL
CORD
YOLK SAC UMBILICAL

ARTERIES
UMBILICAL VEIN
Figs. 16.1, 16.2, and 16.3 Diagrammatic representations of the embryo at 3, 4 and 5 weeks of intra-uterine life. Note
the developing allantosis and omphalomesenteric duct
GI TRACT ALLANTOSIS
CLOACA
UMBILICAL
CORD
OMPHALOMESENTERIC
DUCT UMBILICAL
VEIN
UMBILICAL ARTERIES
Figs. 16.1, 16.2, and 16.3 (continued)
• The urachus varies from 3 to 10 cm in length • Persistence of the umbilical ring results in an
and from 8 to 10 mm in diameter. umbilical hernia.
• It is a three-layered tubular structure, the
innermost layer being lined with transitional
epithelium in 70 % of cases and with columnar 16.3 Classification
epithelium in 30 %.
• The structure is surrounded by connective tis- • There are four types of congenital urachal
sue and an outermost muscular layer in conti- remnant anomalies.
nuity with the detrusor muscle. • They are:
• Occasionally, the urachus may merge with – Patent urachuss(50 %)
one or both of the obliterated umbilical arter- – Urachal cyst (30 %)
ies, and there may be a slight deviation to the – Urachal-umbilical sinus (15 %)
right or left of the midline. – Vesicourachal diverticulum (5 %)
• As the distal hindgut and the urogenital sinus • Urachal cyst:
separate, the developing bladder remains con- – A urachal cyst is a cyst which occurs in a
nected to the allantois through a connection persistent portion of the urachus
called the urachus. between the umbilicus and the urinary
• Persistence of this communication leads to bladder.
urachal remnants. – It presents as an extraperitoneal mass in the
• The urachal remnant anomalies include: umbilical region.
– Patent urachus – Urachal cysts are usually silent clinically
– Urachal sinus until infection, calculi or adenocarcinoma
– Urachal cyst develop
– Urachal diverticulum – It is characterized by:
• Subsequently, the yolk and body stalks fuse to • Abdominal pain, and fever if infected
become the umbilical cord. • It may rupture, leading to peritonitis
• Development of the abdominal wall narrows the • It may drain through the umbilicus.
umbilical ring, which should close before birth.
• Patent urachus:
– This is the commonest congenital malfor-
mation of the urachus.
PATENT
– In patent urachus, the whole urachus fails to URACHUS URINARY
obliterate and there is a patent communication BLADDER
between the urinary bladder and the
umbilicus.
• Umbilical sinus:
– In umbilical sinus, the distal part of the ura-
chus remains open to the umbilicus.
– The usual presentation is persistent umbili-
cal discharge.
• Vesico-urachal diverticulum:
– In this, there is a wide patent urachal open-
ing to the urinary bladder
Fig. 16.4 Diagrammatic representation of a patent
• Inflammation and malignancy are the com- urachus
monest complications of urachal remnants.
• Inflammation occurs more frequently in chil- • Malignant degeneration of urachal remnants
dren and young adults. occurs more frequently in middle-aged and
– Inflammation may be complicated by the older people.
development of an abscess which can
remain clinically unrecognized or it can
present as acute surgical abdomen. 16.4 Clinical Features
– This must be kept in mind as the diagno-
sis often is confused with other diseases • Congenital urachal anomalies are rare and
such as Meckel’s diverticulum, acute occur more common in males than females
appendicitis, recurrent urinary infections, (M:F is 2:1).
or abdominal colicky pain of unknown • The majority of patients with urachal abnor-
origin. malities (except those with a patent urachus)
• The most common infecting pathogens are asymptomatic.
are E. coli and Proteus, but a variety of • However, they may become symptomatic if
other pathogens can also be found, these abnormalities are infected.
including Staphylococcus aureus, • Patent urachus (Figs. 16.4, 16.5, and 16.6):
Bacteroides, Fusobacterium, and – If a persistent communication remains
Streptococcus iridans. between the bladder lumen and the umbili-
• Rarely it is secondary to Actinomycosis, cus, urine leakage is usually noted during
Aspergillus or Tinea corporis. the neonatal period.
• Occasionally, a chronic inflammatory – In about one-third of cases, this condition
process can result in the unusual form of is associated with posterior urethral valves
a xanthogranulomatous urachitis or urethral atresia.
– Patients may also complain of urinary symp- – Some patients with patent urachus are
toms such as suprapubic pain, dysuria, and/ asymptomatic, and sometimes an acquired
or intermittent episodes of urinary obstructive lesion of the lower urinary tract
retention. may result in umbilical-urinary fistulas.
– Infection of a urachal sinus and the cord – A definitive diagnosis can be made with
stump must be taken seriously because of sinography or cystography.
its potential sequelae such as cellulitis, – Patent urachus can also be demonstrated at
necrotizing fasciitis, peritonitis, multiple longitudinal US and occasionally at CT
hepatic abscess, septicaemia, and possible performed in infants during the bladder-
retroperitoneal abscess. filling stage.
Figs. 16.5 and 16.6 Clinical photographs showing patent urachus. Note the catheter inserted through the urethra and
coming out through the patent urachus. Not also the prolapsing urachus in the first photograph
URINARY
URINARY
BLADDER
URACHAL BLADDER
SINUS
BLADDER
DIVERTICULUM
Fig. 16.7 Diagrammatic representation of a urachal sinus

Fig. 16.8 Diagrammatic representation of a vesicoura-
chal diverticulum
• Umbilical-urachal sinus (Figs. 16.7):
– Umbilical-urachal sinus consists of blind
dilatation of the urachus at the umbilical • Intraurachal stone formation
end. • Increased prevalence of carcinoma after
– A small opening into the umbilicus is gen- puberty
erally present. – It is usually discovered incidentally at axial
– This may result in periodic umbilical CT performed for unrelated reasons. It
discharge. appears as a midline cystic lesion just above
• Vesicourachal diverticulum may Vesicourachal the anterosuperior aspect of the bladder.
diverticulum (Fig. 16.8): – On US, it appears as an extraluminally pro-
– In vesicourachal diverticulum, the urachus truding, fluid-filled sac that does not com-
communicates only with the bladder dome. municate with the umbilicus.
– This condition results when the vesical end – In infants, vesicourachal diverticulum is
of the urachus fails to close. commonly accompanied by prune-belly
– Vesicourachal diverticulum is asymptom- syndrome.
atic in most cases. • Urachal cyst (Figs. 16.9, 16.10, 16.11, 16.12,
– It tends to be found in patients with chronic and 16.13):
bladder outlet obstruction. – An urachal cyst develops if the urachus closes
– be complicated by: at both the umbilicus and the bladder but
• Urinary tract infection remains patent between these two endpoints.
– CT or US are helpful for the diagnosis and

shows a fluid-filled cavity in the midline
lower abdominal wall.
– Eggshell calcification of the cyst wall is
URACHAL rarely seen.
CYST
– Infected urachal cyst manifests as wall
thickening and demonstrates an attenua-
URINARY tion higher than that of water at CT and
BLADDER
soft-tissue components and mixed echo-
genicity at US.
16.5 Tumors and Urachal

Fig. 16.9 Diagrammatic representation of a urachal cyst Remnants
• Urachal tumors are extremely rare and can be

benign or malignant.
• Benign urachal tumors include:
– Adenomas
– Fibromas
– Fibroadenomas
– Fibromyomas
– Hamartomas
• Malignant urachal neoplasms represent less
than 0.5 % of all urinary bladder cancers.
Fig. 16.10 Abdominal ultrasound showing a urachal cyst • The normal urachus is commonly lined by tran-
sitional epithelium, but it was found that urachal
– It occurs primarily in the lower one-third of carcinoma predominantly are adenocarcinoma
the urachus and less frequently in the upper (90 % of cases) and 75 % of these cases are
one-third. mucin producing.
– Urachal cysts are usually small but vary • This is probably due to the metaplasia of the
considerably in size. urachal mucosa into columnar epithelium fol-
– They become symptomatic when they lowed by malignant transformation.
enlarge. • The remaining urachal carcinomas are tran-
– Sometimes, they are found as incidental sitional, squamous, or anaplastic
masses during routine examination. carcinomas.
– As with other urachal anomalies, infection • 34 % of bladder adenocarcinomas are of ura-
is the most common complication of urachal origin.
chal cyst, and the majority of cysts are • These tumors are most commonly seen in
infected at the time of diagnosis. patients 40–70 years of age, two-thirds of whom
– Rarely, spontaneous rupture of an infected are men.
cyst into the abdominal cavity leads to • Urachal carcinomas may be solid, cystic, or a
localized or generalized peritonitis. combination of the two.
– Percutaneous needle biopsy or fluid aspiration • Urachal tumors are typically silent because of
is mandatory for diagnosis and treatment. their extraperitoneal location.
– Total exciton of the cyst is essential because • The majority of patients exhibit local invasion
there is a 30 % reinfection rate and carci- or metastatic disease at presentation.
noma may develop in an unresected or • Ninety percent of urachal carcinomas arise in
incompletely resected urachal. cyst. the juxta vesical portion of the urachus and
16.6 Management 399
Figs. 16.11, 16.12, and 16.13 Clinical photograph showing a patient with urachal cyst being excised. Note the loca-
tion of the cyst above the urinary bladder and beneath the anterior abdominal wall
extend superiorly toward the umbilicus and with or without superimposed infection and
inferiorly through the bladder wall. tumors, can be easily demonstrated by abdom-
• A minority of urachal carcinomas are located inal ultrasound.
in the middle of the urachus (6 % of cases) or • CT is more helpful in confirming the diagno-
near the umbilical end (4 %). sis and determining the extent of the disease.
• 50–70 % of urachal carcinomas produce psam-
momatous calcifications that may be punctate,
stippled, or curvilinear and peripheral. 16.6 Management
• The prognosis is generally poor because these
tumors are usually clinically silent and discov- • Asymptomatic remnants are managed
ered late after it has reached a large size and conservatively.
extended locally or metastasized. Metastases • Surgical excision should be avoided for
occur initially in the pelvic lymph nodes, fol- patients younger than 1 year because the rem-
lowed by systemic metastases to the lung, nant might spontaneously disappear.
brain, liver, and bone. • Infective complications of urachal remnants
• It was shown that many of the features of ura- are treated with antibiotic therapy for the acute
chal remnants, including congenital lesions infection followed by surgical excision
• The presence of an abscess requires drainage 2. Chen WJ, Hsieh HH, Wan YL. Abscess of urachal
preferably percutaneous drainage under ultra- remnant mimicking urinary bladder neoplasm. Br
J Urol. 1992;69:510–2.
sound guidance and once the infection sub- 3. Cilento Jr BG, Bauer SB, Retik AB, Peters CA, Atala
sides, the remnant should be excised. A. Urachal anomalies: defining the best diagnostic
• It was reported that up to 30 % of infected ura- modality. Urology. 1998;52:120–2.
chal cysts recurred when not excised. 4. Costakos DT, Williams AC, Love LA, Wood BP. Patent
urachal duct. Am J Dis Child. 1992;146:951–2.
• It is generally recommended that all urachal 5. Goldman IL, Caldamone AA, Gauderer M, et al.
remnants should be excised to avoid recurrent Infected urachal cysts: a review of 10 cases. J Urol.
infection and because of possible malignant 1988;140:375–8.
transformation later in life. 6. Iuchtman M, Rahav S, Zer M, Mogilner J, Siplovich
L. Management of urachal anomalies in children and
• Surgical excision is usually done through a adults. Urology. 1993;42:426–30.
transverse or midline infra-umbilical incision. 7. Lee SH, Kitchens HH, Kim BS. Adenocarcinoma of
• Recently and as a result of advances in mini- the urachus: CT features. J Comput Assist Tomogr.
mal invasive surgery, laparoscopic excision 1990;14:232–5.
8. Mesrobian HGO, Zacharias A, Balcom AH, Cohen
of urachal remnants was shown to be feasi- RD. Ten years of experience with isolated urachal
ble and safe. The advantages of laparoscopic anomalies in children. J Urol. 1997;158:1316–8.
excision of urachal remnants include: 9. Nagasaki A, Handa N, Kawanami T. Diagnosis of
– It minimizes the morbidity associated with urachal anomalies in infancy and childhood by con-
trast fistulography, ultrasound and CT. Pediatr Radiol.
open surgery 1991;21:321–3.
– A shorter hospital stay 10. Sadler TW. The embryologic origin of ventral body
– Faster recovery wall defects. Semin Pediatr Surg. 2010;19(3):209–14.
– Better cosmetic result
Further Reading
1. Boothroyd AE, Cudmore RE. Ultrasound of the dis-
charging umbilicus. Pediatr Radiol. 1996;26:362–4.
Inguinal Hernias and Hydroceles
17
17.1 Introduction 17.2 Inguinal Hernia
• Hippocrates used the Greek hernios for bud or 17.2.1 Incidence

bulge to describe abdominal hernias.
• Abdominal wall hernias are protrusions of • The exact incidence of indirect inguinal hernia
abdominal contents through a defect or weak- in infants and children is unknown.
ness in the abdominal wall. • The incidence of hernias is about 10–20 per
• Abdominal wall hernias are among the most 1,000 live births and is much more common in
common of all surgical problems in infants prematures.
and children. • Indirect inguinal hernias are more common on
• There are several different types of abdominal the right side and about 60 % of hernias occur
wall hernias in infants and children on the right side (Figs. 17.1 and 17.2).
including: • Premature infants are at increased risk for
– Inguinal hernia inguinal hernia, with incidence rates of 2 % in
– Umbilical hernia females and 7–30 % in males.
– Paraumbilical hernia • Approximately 5 % of all males develop a her-
– Epigastric hernia nia during their lifetime.
– Femoral hernia • Inguinal hernias are much more common in
– Spigelian hernia males than in females.
– Lumbar hernia • The male-to-female ratio is estimated to be
– Incisional hernia 4–8:1.
– Other rare hernias • Moreover, the risk of incarceration of inguinal
• The management of abdominal wall hernias hernia is more than 60 % in prematures.
are different and depend on the type of hernia, • Inguinal hernias:
age of the patient and mode of presentation. – 60 % are on the right side.
• All pediatric inguinal hernias require opera- – 30 % are on the left side.
tive treatment to prevent the development of – 10 % are bilateral (Figs. 17.3 and 17.4)
complications, such as inguinal hernia incar- – Anatomically speaking, indirect and direct
ceration or strangulation. inguinal hernias differ in that the direct

402 17 Inguinal Hernias and Hydroceles
Figs. 17.1 and 17.2 Clinical photographs showing a large right and left inguinal hernia
Figs. 17.3 and 17.4 A clinical photograph showing bilateral inguinal hernias
hernia bulges through the inguinal floor 17.2.2 Etiology

medial to the inferior epigastric vessels and
the indirect hernia arises lateral to the infe- • Inguinal hernias are congenital.
rior epigastric vessels. • Embryologically, the processus vaginalis is an
– Inguinal hernia can be complete where the outpouching of peritoneum attached to the
whole sac descends into the scrotum and testicle that trails behind as it descends retro-
surrounds the tesis (Scrotal hernia) or peritoneally into the scrotum.
incomplete where the hernial sac ends up • Normally, the processus vaginalis obliterates.
in the inguinal canal above the testis • When obliteration of the processus vaginalis
(Inguinal hernia) (Fig. 17.5). fails to occur, inguinal hernia results.
17.2 Inguinal Hernia 403
Fig. 17.5 Diagrammatic

representation of the
classic inguinal hernia and
inguinal hernia extending
into the scrotum (scrotal
hernia)
INGUINAL
HERNIA
SCROTAL
HERNIA
• Increased intra-abdominal pressure is seen in – Cystic fibrosis

a variety of conditions and also contribute to – Connective tissue disease
the appearance of inguinal hernia. – Mucopolysaccharidosis
• Elevated intra-abdominal pressure is associ- – Congenital dislocation of the hip
ated with chronic cough, ascites, increased – Ehlers-Danlos syndrome
peritoneal fluid from biliary atresia, peritoneal – Marfan syndrome
dialysis or ventriculoperitoneal shunts, intra- – Fetal hydrops
peritoneal masses or organomegaly, and – Liver disease with ascites
constipation. – Ventriculoperitoneal shunting for
• Other conditions with increased incidence of hydrocephalus
inguinal hernias are:
– Exstrophy of bladder.
– Neonatal intraventricular hemorrhage. 17.2.3 Clinical Features
– Myelomeningocele.
– Undescended testes. • The parents of infants and children with an
• The following conditions are associated with inguinal hernia present with the history of a
an increased risk of inguinal hernia: swelling that is commonly intermittent, in the
– Prematurity and low birth weight. inguino-scrotal region in boys and inguino-
– Urologic conditions: labial region in girls.
• Cryptorchidism • The swelling commonly occurs after crying or
• Hypospadias straining.
• Epispadias • Sometimes, they present with an obvious
• Exstrophy of the bladder swelling at the inguinal region or sometimes
• Ambiguous genitalia within the scrotum in boys (Fig. 17.6).
• Cloacal exstrophy • The hernia may be bilateral (Figs. 17.7 and
– Patent processus vaginalis, which may be 17.8)
present because of increased intraabdomi- • The swelling is painless and reducible in a
nal pressure due to ventriculoperitoneal simple inguinal hernia.
shunts, peritoneal dialysis, or ascites • The presence of a painful swelling suggests an
– Abdominal wall defects incarcerated inguinal hernia.
• Gastroschisis • Patients with an incarcerated hernia gen-
• Omphalocele erally present with a tender firm mass in
– Family history the inguinal canal or scrotum that is
– Meconium peritonitis irreducible.

photograph showing an
incarcerated right inguinal INGUINAL
hernia. Note also the left HERNIA
hydrocele
HYDROCELE
Figs. 17.7 and 17.8 Clinical photographs showing bilateral incarcerated inguinal hernia
• Silk sign: When the hernia sac is palpated over 17.2.4 Variants of Hernia
the cord structures, the sensation may be simi-
lar to that of rubbing two layers of silk 1. Indirect inguinal hernia:
together. • Indirect inguinal hernias occur when the
• This finding is known as the silk sign and abdominal contents protrude through the
is highly suggestive of an inguinal deep inguinal ring, lateral to the inferior
hernia. epigastric vessels.

representation of a
Littre’ hernia
MECKEL
DIVERTICULUM
IN A HERNIAL SAC

representation of a
Richter’s hernia
PART OF THE
BOWEL WALL
• It is caused by failure of embryonic closure containing a diverticulum of the small

of the processus vaginalis. bowel.
2. Direct inguinal hernia: 4. Sliding inguinal hernia:
• This type of inguinal hernia, enters through • A sliding inguinal hernia occurs when the
a weak point in the transversalis fascia of wall of the hernia sac is made up of an
the abdominal wall, and its sac is noted to organ like the urinary bladder or colon.
be medial to the inferior epigastric vessels. • It is a variant that is seen in 3 % of hernia cases.
• Direct inguinal hernias may occur in males 5. Richter’s hernia (Fig. 17.10):
or females, but males are ten times more • A Richter’s hernia occurs when the
likely to get a direct inguinal hernia. antimesenteric wall of the intestine pro-
• These hernias are capable of exiting via the trudes through a hernial defect.
superficial inguinal ring but, unlike indirect • The first scientific description of this her-
inguinal hernias, they cannot descend into nia was by August Gottlob Richter in 1778.
the scrotum. • A Richter’s hernia can result in strangula-
3. Littre’s hernia (Fig. 17.9): tion and necrosis in the absence of intesti-
• A Littre’s hernia is a hernia containing a nal obstruction.
Meckel’s diverticulum. • It is a relatively rare but dangerous type of
• Littre’s hernia was first described by the hernia.
French surgeon Alexis Littré in 1700. 6. Busse’s hernia (Fig. 17.11):
• He described three cases from cadaverous • An inguinal hernia in which the testicle is
studies of incarcerated femoral hernias within the hernia sac.
7. Maydl’s hernia (Fig. 17.12): • This intervening portion of bowel becomes

• This is seen when two adjacent loops of deprived of its blood supply and eventually
small intestines are within a hernial sac becomes ischemic and necrotic.
with a tight neck. • Perforation of this part of intestine will
• The intervening portion of bowel lies lead to peritonitis and the patient present
within the abdomen with an acute abdomen.
8. Amyand’s hernia (Fig. 17.13):
• The content of the hernial sac is the vermi-
form appendix.
17.2.5 Complications of Inguinal

Hernias
1. Incarceration:
• The herniated bowel in inguinal hernia can
become swollen, edematous and engorged
within the hernial sac.
• The hernia becomes irreducible and causes
intestinal obstruction in infants and chil-
dren (Figs. 17.14, 17.15, 17.16, and 17.17).
• Every attempt should be made to reduce it
manually.
• Incarceration occurs in 17 % of right-sided
hernias and 7 % of left-sided hernias.
• More than 50 % of cases of incarceration
occur within the first 6 months of life;
the risk gradually decreases after age
1 year.
• Premature infants have twice the risk of
Fig. 17.11 Diagrammatic representation of Busse’s incarceration than the general pediatric
hernia population.
MAYDLE’S HERNIA
Fig. 17.12 A diagram-

matic representation of
Maydle’s hernia
Fig. 17.13 A diagrammatic

representation of
Amyand’s hernia
APPENDIX IN A
HERNIAL SAC
Figs. 17.14, 17.15, 17.16, and 17.17 Clinical photographs showing irreducible inguinal hernias
Fig. 17.18 An intraoperative photograph

showing irreducible hernia containing the ovary
which was swollen
OVARY
• More than two thirds of all incarcera- – Today, most surgeons do not routinely
tions occur in children younger than perform a contralateral exploration unless
1 year. a contralateral inguinal hernia or patent
• Girls are more likely to develop incarcera- processus vaginalis can be demonstrated
tion of an inguinal hernia; the incidence in either by preoperative ultrasonography or
girls is 17.2 %, whereas the incidence in intraoperative laparoscopy.
boys is 12 % (Fig. 17.18). – A hernia develops in the other side of the
2. Strangulation (Figs. 17.19, 17.20, and 17.21): groin in up to 30 % of children who have
• Once the vascular supply of the herniated had hernia surgery. This is more so if the
contents becomes compromised, the hernia initial hernia was on the left side.
becomes strangulated. – When an inguinal hernia is present, some
• This may lead to ischemic necrosis and pediatric surgeons perform a contralateral
intestinal perforation. groin exploration.
• This is an indication for emergency surgi- – This is to detect an occult patent processus
cal exploration. vaginalis that may lead to a hernia on the
• A rare complication of inguinal hernia is opposite side (metachronous contralateral
migration of ventriculoperitoneal shunt hernia). This is present in less than 5 % of
into the hernial sac (Figs. 17.22 and cases.
17.23). – The Goldstein test can be used to determine
when to perform a contralateral exploration. In
this test, the abdomen is insufflated with gas
17.2.6 Treatment through the already open hernia sac. Crepitus
in the opposite groin is a positive test result,
• All pediatric inguinal hernias require opera- suggesting a contralateral patent processus
tive treatment to prevent the development of vaginalis and warranting a contralateral explo-
complications, such as incarceration or ration. This test may not be conclusive.
strangulation. – An alternative approach is laparoscopy
• Most inguinal herniatomies are performed on which can be used to detect an occult con-
an outpatient basis. tralateral patent processus vaginalis.
• Laparoscopic hernia repair in children is not – This can be done through a separate inci-
performed as commonly as in adults. sion at the umbilicus or through the already
• Contralateral inguinal hernia exploration: opened hernia sac. This allows inspection
– There is controversy about whether the of the contralateral inguinal ring and
contralateral groin should be explored. assessment of its patency.
Figs. 17.19, 17.20, and 17.21 Clinical photographs showing a strangulated inguinal hernia. Note the colour of the
intestine as a result of strangulation and the strangulated gangrenous ovary
Figs. 17.22 and 17.23 Clinical intraoperative photographs showing a ventriculoperitoneal shunt in the inguinal her-
nial sac
17.2.7 Complications of Inguinal • The occurrence of a metachronous contralat-

Herniotomy eral hernia is inversely related to age and can
be as high as 12 %. This is more so if the initial
• The overall operative complication rate asso- hernia was on the left side.
ciated with hernias is 1.7–8 %.
• Infertility:
– Infertility may result from bilateral injury 17.3 Hydrocele
to the vas deferens or injury to the vas of a
solitary testis. 17.3.1 Embryology
– The presence of a vas-like structure in the
pathology specimen does not necessarily • During fetal development, the testicle devel-
indicate injury to the vas, as up to 6 % of ops below the kidney, within the peritoneal
specimens contain müllerian ductal cavity.
remnants with a histologic appearance very • Subsequently, the testicle descends down and
similar to the vas. through the inguinal canal and finally into the
• Testicular atrophy: scrotum.
– An incarcerated hernia may compromise • During its descent, it is accompanied by an
blood flow to the testicle prior to surgery. extension of peritoneum (the processus
– The rate of testicular atrophy after repair of vaginalis).
an incarcerated hernia can be as high as 19 %. • Normally, the processus vaginalis obliterates
– Testicular atrophy may also result from and becomes a fibrous cord.
intraoperative injury to the testicular blood • The distal part of the processus vaginalis
supply. forms the tunica vaginalis. In postnatal life,
• Scrotal hematoma: this is a potential space that should not com-
– As with any surgery, scrotal hematomas municate with the peritoneal cavity of the
may occur. abdomen.
– A hematoma usually does not need to be • If the processus vaginalis does not close, it is
explored unless the hematoma continues to referred to as a patent processus vaginalis.
enlarge or becomes infected. • If the patent processus vaginalis is small in
– Treatment is with scrotal elevation and caliber and allow fluid to pass from the
analgesics. abdomen, the condition is referred to as a
• Wound infection. communicating hydrocele.
• Hypesthesia and neuropathic pain can result • If the patent processus vaginalis is larger,
from nerve entrapment or injury. allowing ovary, intestine, omentum, or other
• Iatrogenic cryptorchidism: abdominal contents to protrude, the condition
– This may result from excessive scar forma- is referred to as a hernia.
tion and ascent of the testicle. • A hydrocele usually transilluminates on
– Or improper replacement of the testicle examination. However, gas-filled intestines
into the scrotum after herniotomy. also transilluminate. This must be considered
• Recurrence and hydrocele formation: during evaluation (Fig. 17.24).
– This may be seen in less than 5 % of cases. • Hydroceles can be unilateral or bilateral
– If the hydrocele does not disappear sponta- (Figs. 17.25, 17.26, and 17.27)
neously after 1 year, reoperation is • An important point differentiating a hydro-
indicated. cele from an inguinal hernia is that you
– With open surgery, ipsilateral recurrence can get above a hydrocele but you cannot
rates are less than 1 %. get above an inguinal hernia. The only
– The ipsilateral recurrence rate following exception to this is an abdomino-scrotal
laparoscopic inguinal hernia repair is 3.4 %. hydrocele.
17.3 Hydrocele 411
17.3.2 Classification of Hydroceles – Actions which increase intra-abdominal

(Fig. 17.28) pressure (crying, coughing, etc.) will also
lead to increase in the size of the hydrocele.
• Communicating hydroceles: • Noncommunicating hydroceles:
– The patent processus vaginalis is continu- – In this, the fluid is confined to the scrotum
ous with the tunica vaginalis, which sur- within the tunica vaginalis.
rounds the testicle. – The processus vaginalis is obliterated so
– The communication is small, so only fluid the fluid does not communicate with the
can pass into the patent processus vaginalis. abdominal cavity.
– A characteristic feature of communicating – Such hydroceles are common in infants,
hydroceles is their tendency to be relatively and the hydrocele disappears before the
small in the morning and increase in size infant is 1 year old.
during the day.
Fig. 17.24 A clinical photograph showing tansillumina- Fig. 17.27 A clinical photograph showing giant bilateral
tion of a hydrocele hydroceles
Figs. 17.25 and 17.26 Clinical photographs showing small and large bilateral hydroceles
– They may be present at birth or develop in – This is a fluid filled cystic swelling within the
older children. inguinal canal.
– The fluid in noncommunicating hydroceles – The fluid does not extend into the scrotum.
is walled off, the size of the hydrocele is – This occurs when the processus vaginalis
generally stable and does not change with obliterates above the testicle and a small com-
change in intra-abdominal pressure. munication with the peritoneum persists, and
• Reactive hydroceles: the processus vaginalis may be open as far
– These are noncommunicating hydroceles down as the top of the scrotum.
that develop following trauma or • Hydrocele of the canal of Nuck:
infection. – This occurs in girls when fluid accumulates
• Encysted hydrocele of the cord (Figs. 17.29 within the processus vaginalis in the ingui-
and 17.30): nal canal.
Fig. 17.28 A diagram-

matic representation
of the different types
of hydroceles
COMMUNICATING NON-COMMUNICATING ENCYSTED

HYDROCELE HYDROCELE HYDROCELE
ENCYSTED
HYDROCELE
ENCYSTED
HYDROCELE
Figs. 17.29 and 17.30 Clinical and intraoperative photographs showing encysted hydrocele
17.3 Hydrocele 413
• Abdomino-scrotal hydrocele: 17.3.3 Treatment

– This results from a miniscule opening in
the processus vaginalis. • Unlike hernias, many newborn hydroceles
– The fluid enters the hydrocele and becomes resolve because of spontaneous closure of the
trapped. patent processus vaginalis (Figs. 17.31, 17.32,
– The hydrocele continues to enlarge and and 17.33).
eventually extends upward into the abdo- • The noncommunicating hydrocele:
men, causing a fluid-filled mass in the – The fluid in the hydrocele is usually reab-
abdomen. sorbed before the infant reaches age 1 year.
– Observation is often appropriate for hydro-
celes in infants.
• In 95 % of congenital hydroceles, the natural
history is one of gradual and complete resolu-
tion by 1 year of age.
• For those lasting longer than 1 year or for those
non-communicating hydroceles that manifest
after the first year, surgical repair is indicated
since these rarely resolve spontaneously
• Indications for hydrocele repair:
– Congenital hydroceles that fails to resolve
by age 2 years.
– Non-communicating hydroceles that mani-
fest after 1 year of age.
Fig. 17.31 A clinical photograph showing an infant with – Continued discomfort and enlargement.
bilateral hydroceles – Secondary infection (very rare)
Figs. 17.32 and 17.33 Clinical photographs of congenital hydrocele being treated conservatively
Further Reading 5. Lukong CS. Surgical techniques of laparoscopic

inguinal hernia repair in childhood: a critical appraisal.
J Surg Tech Case Rep. 2012;4(1):1–5.
1. Brandt ML. Pediatric hernias. Surg Clin North Am.
6. McClain L, Streck C, Lesher A, Cina R, Hebra A.
2008;88(1):27–43, vii–viii.
Laparoscopic needle-assisted inguinal hernia repair in
2. Dutta S, Albanese C. Transcutaneous laparoscopic
495 children. Surg Endosc. 2015;29(4):781–6.
hernia repair in children: a prospective review of 275
7. Merriman TE, Auldist AW. Ovarian torsion in ingui-
hernia repairs with minimum 2-year follow-up. Surg
nal hernias. Pediatr Surg Int. 2000;16:383.
Endosc. 2009;23(1):103–7.
8. Schier F, Montupet P, Esposito C. Laparoscopic ingui-
3. Esposito C, St Peter SD, Escolino M, Juang D, Settimi A,
nal herniorrhaphy in children: a three-center experience
Holcomb 3rd GW. Laparoscopic versus open inguinal
with 933 repairs. J Pediatr Surg. 2002;37(3):395–7.
hernia repair in pediatric patients: a systematic review.
9. Timberlake MD, Herbst KW, Rasmussen S, Corbett
J Laparoendosc Adv Surg Tech A. 2014;24(11):811–8.
ST. Laparoscopic percutaneous inguinal hernia repair
4. Lao OB, Fitzgibbons Jr RJ, Cusick RA. Pediatric
in children: review of technique and comparison with
inguinal hernias, hydroceles, and undescended testi-
open surgery. J Pediatr Urol. 2015;1:262.e1–6.
cles. Surg Clin North Am. 2012;92(3):487–504, vii.
Cloacal Exstrophy
18
18.1 Introduction – The associated omphalocele may be major

or minor and sometimes no associated
• Cloacal exstrophy is an extremely rare and omphalocele.
major birth defect representing the severe end – Malrotation
of the spectrum of the exstrophy-epispadias – The symphysis pubis is widely separated
complex (Fig. 18.1). – The pelvis is often asymmetrically shaped
• It is also called vessico-intestinal fissure. – The genitalia (ambiguous genitalia):
• The exact incidence of cloacal exstrophy is • In males, the penis is divided into two
not known but the estimated prevalence halves usually located separately on
ranges from 1 in 50,000 to 250,000 live either side of the bladder plates with the
births. adjacent scrotal halves.
• It is more common in males than females • In females, the clitoris is divided into
(a male-female ratio of 2:1). two haves usually located separately on
• Cloacal exstrophy, is also called the OEIS either side of the bladder plates with the
Complex: adjacent part.
– O: Omphalocele • Duplication of the vagina and uterus
– E: Exstrophy of the cloaca • Vaginal agenesis
– I: Imperforate Anus
– S: Spinal Defects
• Clinically, patients with cloacal exstrophy 18.2 Etiology and Pathogenesis
present at birth and it is characterized by the
followings spectrum of anomalies (Figs. 18.2, • The exact etiology of cloacal exstrophy is not
18.3, 18.4, 18.5, and 18.6): known.
– Two exstrophied hemibladders • Several theories have been proposed to explain
– These are separated by a foreshortened the pathogenesis of cloacal exstrophy but
hindgut or cecum none of them can fully explain the spectrum of
– The hindgut is often blind-ending resulting anomalies seen in cloacal exstrophy.
in an imperforate anus. • The most accepted theory is that cloacal
– This extrophied ileo-cecal region presents exstrophy results from premature rupture of
between the two hemi bladders (the “ele- the cloacal membrane prior to caudal migra-
phant trunk” appearance). tion of the urorectal septum, and failure of
– Omphalocele fusion of the genital tubercles.

416 18 Cloacal Exstrophy
Fig. 18.1 Clinical photo-

graph showing the compo- OMPHALOCELE
nents of the cloacal
exstrophy HEMIBLADDER
HEMIBLADDER
ILEOCECAL REGION
Figs. 18.2 and

OMPHALOCEL
18.3 Clinical photographs
showing two patients with HEMIBLADDER HEMIBLADDER
cloacal exstrophy. Note the
difference in the size of
omphalocele and also the
extent of the exstrophied
ileo-cecal region
ILEOCECAL REGION
OMPHALOCELE
HEMIBLADDER
HEMIBLADDER
ILEOCECAL REGION
• Embryo logically: cloacal membrane persists leading to poor

– The urorectal septum divides the cloaca lower abdominal wall development.
into an anterior urogenital sinus and a pos- – The cloacal membrane eventually ruptures
terior anorectal canal. but if this happens prior to the descent of the
– This occurs around the fourth week of urorectal septum which happens at 6–8 weeks
intrauterine life and simultaneously, the of gestation, then cloacal exstrophy results.
cloacal membrane is invaded by lateral – Cloacal exstrophy develops as a result of:
mesodermal folds. • Failure of the urorectal septum to
– It is postulated that if this mesodermal develop and divides the urogenital sinus
invasion does not occur, the infraumbilical anteriorly from the rectum posteriorly.
Figs. 18.4 and

18.5 Clinical NO OMPHALOCELE
photographs showing
cloacal exstrophy in
two patients. Note the
absence of omphalocele OPENED
in the first one and URINARY
associated anorectal BLADDER
agenesis in the second
one
PROLAPSED
ILEOCECAL
REGION
PROLAPSED
ILEOCECAL
OPENED REGION
URINARY
BLADDER
ANORECTAL
AGENESIS
HEMIBLADDER
each with its ipsilateral ureter, and anorec-
tal agenesis.
– The pubic bones are widely separated, and
spinal dysraphism is common in these
HEMIBLADDER patients.
ANORECTAL
AGENESIS
18.3 Associated Anomalies
Fig. 18.6 A clinical photograph showing cloacal exstro-
phy. Note the associated anorectal agenesis • Cloacal exstrophy is commonly associated
with other anomalies including cardiovascu-
• Failure of the mesoderm forming the lar, and central nervous system anomalies.
infraumbilical abdominal wall to pro- • Omphalocele is present in 70–90 % of patients
liferate and form the lower abdomi- with cloacal exstrophy.
nal wall • Spinal and skeletal anomalies (46 %). These
• Failure of the genital tubercle to develop. include (Figs. 18.7 and 18.8):
• Failure of these events to occur results – Hemivertebra
in exstrophy of both bladder and – Myelomeningocele
intestine. – Clubfoot deformities
– Classically, cloacal exstrophy is made up – Absence of feet
of omphalocele, exstrophied ileocecal – Tibial/fibular deformities
region of bowel, exstrophied hemi bladders – Hip dislocation
• Upper urinary tract anomalies (42 %).

– Pelvic kidney
– Horseshoe kidney
– Hypoplastic kidney
– Solitary kidney
• Malrotation (30 %)
– Urological malformations:
• Ureteropelvic junction obstruction
• Ectopic pelvic kidney
• Horseshoe kidney
• Hypoplastic kidney or renal agenesis
• Megaureter
• Ureteral ectopy and ureterocele
• Lower extremity anomalies (30 %)
• Double appendix (30 %)
Fig. 18.7 Clinical photograph of a newborn with cloacal
• Absent appendix (21 %)
exstrophy. Note also the associated bilateral tallipes • Short bowel syndrome (19–46 %)
equinovarus • Gastrointestinal duplications
• Small bowel atresia (5 %)
• Abdominal wall musculature deficiency (1 %)

and Management
• Cloacal exstrophy is a very rare and complex

anomaly of the urogenital tract and intestinal
tract resulting in exstrophy of both bowel and
bladder (Fig. 18.9).
• Commonly in cloacal exstrophy, the exstro-
phied bowel is the ileo-cecal region with little
or no large bowel distally, but there are cases
where there is colonic exstrophy with suffi-
cient large bowel length. A small colon usu-
ally ends blindly in the pelvis, and the terminal
ileum often prolapses out of the exposed
cecum (Figs. 18.10 and 18.11).
• The presence of enough large bowel is advan-
tageous from the reconstruction point of view.
• The extrophied ileo-cecal region and in the
presence of short large bowel should be pre-
served for reconstruction of the anorectal
malformation.
Fig. 18.8 Abdominal x-ray showing widened pubic bone • Every effort should be made to preserve all
and abnormal asymmetrical pelvis
large intestines because not only it can be used
for bladder augmentation which is necessary
– Sacralization of L5 in the majority of these patients to increase the
– Congenital scoliosis bladder compliance, but also for reconstruction
– Sacral agenesis of the anorectal malformation and vaginal
– Interpedicular widening reconstruction in those who have vaginal
18.4 Clinical Features and Management 419

photograph showing
cloacal exstrophy. Note the
prolapsing terminal ileum
out of the exposed cecum
HEMIBLADDER
HEMIBLADDER
PROLAPSED
TERMINAL ILEUM
Figs. 18.10 and 18.11 A clinical photograph showing region with the terminal ileum open with meconium pass-
cloacal exstrophy. Note the omphalocele, the urinary ing from it. Note the large size of the associated
bladder into two halves and the prolapsed ileo-cecal omphalocele
agenesis or those undergoing gender reassign- • In genetic males with cloacal exstrophy, the
ment (Figs. 18.12, 18.13, 18.14, and 18.15). phallic structures are usually small and com-
• Add to this the valuable absorptive function of pletely bifid with insufficient phallic tissue to
the large bowel. reconstruct an adequate penis.
• Augmentation of the urinary bladder may be • There is now general consensus that genetic
performed using the hindgut if enough length is males with insufficient phallus be gender reas-
available, ileum, or part of the stomach. In the signed as phenotypic females, and to mini-
absence of large intestine, both small bowel and mize testosterone imprinting on the nervous
stomach can be used for bladder augmentation system, this should be done in the immediate
but gastrocytoplasty was shown to be superior. newborn period with early orchidectomy.
• Gender assignment is one of the difficult tasks • Males with adequate bilateral or unilateral
in the management of newborns with cloacal phallic structures should however, be raised as
exstrophy. males.
• Genetic females should not raise a problem as • In the classic repair of cloacal exstrophy in
they will be raised as females. males an epispadias is created initially after
Figs. 18.12 and 18.13 Clinical photographs showing cloacal extrophy. Note the prolapsed bowel and also the abdom-
inal wall defect but no clear omphlocele. The bladder defect is covered by the large prolapsing bowel
DIVIDED ILEOSTOMY
ILEUM
URETERIC
URETERIC CATHETER
CATHETER
HEMIBLADDER
URETERIC Fig. 18.15 Clinical intraoperative photograph showing a

CATHETER diverting ileostomy and ureteric catheters prior to closure
of the urinary bladder
Fig. 18.14 A clinical intraoperative photograph of cloa-
cal exstrophy being repaired. Note the two ureteric cathe-
ters inserted and the mobilized urinary bladder. Note also
• This, however, requires a team approach
the divided ileum to form an ileostomy. Part of the bowel
is left in the posterior wall of the urinary bladder for blad- including:
der augmentation – Neonatologists
– Pediatric surgeons
urinary bladder closure. This is repaired later – Pediatric urologist
and will require the use of long acting testos- – Neurosurgeons
terone to increase the size and length of the – Pediatric orthopedic surgeons
penis. – Geneticists
• The management of newborns with cloacal – Social workers
exstrophy has progressed over the years, and – Stomatherapist
now a very reasonable outcome is expected in • Although there are general guidelines in manag-
most cases. ing newborns with cloacal exstrophy, after thor-
Further Reading 421
ough evaluation of the anatomical abnormalities, – Reapproximating, closing, or leaving the

the management should be individualized. exstrophied bladder undisturbed.
• Immediate management is directed to the • The importance of creating a colostomy
medical stabilization of the infant. instead of an ileostomy is to be emphasized.
• Evaluation and appropriate management of This is to prevent problems with diarrhea,
associated malformations should be undertaken. dehydration, and acidosis. An ileostomy in
• For infants who have few other associated these patients will lead to failure to thrive and
malformations and are medically stable, sever skin excoriations.
staged closure can be considered.
• The bowel should be moistened with saline
and covered with protective plastic dressing.
• Evaluation of the genitalia and gender assignment Further Reading
should be made by a gender assignment team,
including a pediatric urologist, pediatric surgeon, 1. Lund DP, Hendren WH. Cloacal extrophy: experience
with 20 cases. J Pediatr Surg. 1993;28:1360–9.
pediatrician, and pediatric endocrinologist. 2. Manzoni GA, Ransley PG, Hurwitz RS. Cloacal extro-
• Consultation of social worker, pediatric ortho- phy and cloacal extrophy variants: a proposed system
pedic surgeon and other disciplines should be of classification. J Urol. 1987;138:1065–8.
obtained. 3. Ricketts RR, Woodard JR, Zwiren GT, Andrews HG,
Broeker BH. Modern treatment of cloacal extrophy.
• The initial operation consists of: J Pediatr Surg. 1991;26:444–50.
– Separating the bowel from the bladder to 4. Stolar CJH, Randolph JG, Flanigan LP. Cloacal extro-
create an intestinal stoma. phy: individualized management through a staged sur-
– Closing the omphalocele. gical approach. J Pediatr Surg. 1990;25:505–7.
Posterior Urethral Valve
19
19.1 Introduction • An increasing number of cases are diagnosed

antenatally.
• Posterior urethral valve (PUV) disorder is an • Patients with PUVs have a higher incidence of
obstructive developmental anomaly of the cryptorchidism when compared to normal
male urethra. patients.
• It is characterized by a congenital membrane • Other known associated anomalies include
obstructing the posterior male urethra. VATER or VACTERL and rarely ano-rectal
• As a result of urinary obstruction, there is a malformation.
backward pressure and reverse urinary flow • Prenatal intervention in those with PUV does
which can affect the urethra, bladder, ureters, not appear to confer a benefit in the long-term
and kidneys (Fig. 19.1). outcome of renal function.
• Hugh Hampton Young published the first • Primary valve ablation is the recommended
description of posterior urethral valves (PUVs) treatment of choice with diversion being
in 1919. reserved for specific individual cases.
• PUVs occur exclusively in males. The homo- • The most life-threatening problem in the new-
log to the male verumontanum from which the born period is the potential pulmonary hypo-
valves originate is the female hymen. plasia related to in utero oligohydramnios and
• It is considered the most common cause of renal dysfunction. These patients may present
bladder outlet obstruction in male newborns. with pneumothoraces at birth which will com-
• The incidence of posterior urethra is 1 in plicate their pulmonary management.
5,000–8,000 live male newborns. • Newborns are also susceptible to urosepsis as
• The valve is believed to result from abnormal a result of urinary stasis.
embryologic development of the fetal poste- • The presentation of PUV is variable depend-
rior urethra. ing on the degree of obstruction and the
• PUV mechanically obstruct normal bladder spectrum of renal dysfunction and subsequent
emptying and increases voiding pressures. functional outcomes also vary widely.
• The disorder varies in degree of obstruction • A significant number of boys with PUV will
from mild to severe incompatible with postna- develop chronic kidney disease and end stage
tal life. renal failure.
• Severe posterior urethral valves are known to • This is attributed to its consequences,
be associated with renal and respiratory fail- including:
ure from lung underdevelopment as result of – Renal dysplasia
low amniotic fluid volumes. – Upper urinary tract dilatation

424 19 Posterior Urethral Valve
Fig. 19.1 A voiding

posterior urethral valve.
Note the dilated posterior
urethra with the valve, the
associated bladder
diverticulum and right side
vesicoureteric reflux VESICOURETERIC
REFLUX
URINARY
BLADDER
BLADDER
DIVERTICULUM
POSERIOR
URETHRA
ANTERIOR
WITH VALVE
URETHRA
– Vesico-ureteric reflux 19.2 Embryology

– Urinary tract infection
– Bladder dysfunction • Embryologically, the most caudal end of the
• PUV accounts for 25–30 % of pediatric renal Wolffian duct is absorbed into the primitive
transplantations. cloaca at the site of the future verumontanum
• The VURD (valves unilateral reflux dysplasia) in the posterior urethra.
syndrome: • In healthy males, the remnants of this process
– This was described by Hoover and are the posterior urethral folds, called plicae
Duckett. colliculi.
– It results in very poor or non-function of • The embryological abnormality giving rise to
the kidney on the refluxing side with a rela- posterior urethral valves is not well known.
tive sparing of renal function on the contra- • It has been suggested that posterior urethral
lateral, non-refluxing side. valves result from fusion of the plicae colliculi
– The authors also postulated that this mech- (posterior urethral folds) between the
anism of ‘pop-off’ results in long-term nor- entrances of the seminal vesicles at the
mal renal function, as the contralateral veromontanum, and extend to the membra-
kidney is spared and normal. nous urethra.
– This hypothesis was subsequently chal- • PUVs are formed at approximately 4 weeks’
lenged by Cuckow et al. who showed with gestation, as the Wolffian duct fuses with the
serum creatinine and GFR measurements developing cloaca.
that renal function was impaired in cases • There are several theories explaining the
with VURD, implying that the protection embryological origin of PUVs:
offered by the ‘pop-off’ mechanism was – PUVs may represent an anomalous inser-
not complete tion of the mesonephric duct into the
uro-genital sinus, preventing normal – Hypertrophy and hyperplasia of the detru-

migration of these ducts and their anterior sor muscle of the urinary bladder and
fusion. increases in connective tissue limit bladder
– PUVs may represent an abnormality of the compliance during filling.
cloacal membrane. – As a result of this, bladder emptying occurs
• Early classification of PUV was done by Hugh at high intravesical pressures.
Hampton Young in 1919, who described three – This high intravesical pressure, in turn, can
types of PUVs, I–III based on post-mortem be transmitted to the ureters and up into the
dissection studies. renal collecting system and kidneys.
• Subsequently, Dewan et al. suggested a more – The end result of this is increased suscepti-
uniform and similar appearance to the bility to incontinence, infection, and pro-
obstructing posterior urethral membrane. gressive renal damage.
• Their endoscopic appraisal revealed the mem- – The bladder dysfunction may cause ongo-
brane to attach posteriorly, just distal to the ing and progressive renal deterioration.
verumontanum. The membrane extended – Renal insufficiency is caused by PUVs in
anteriorly and obliquely beyond the external approximately 10–15 % of children under-
sphincter with a variable sized aperture located going renal transplantation, and approxi-
within it, at the level of the verumontanum. mately one third of patients born with PUVs
• They described the membrane as congenital progress to end-stage renal disease (ESRD).
obstructing posterior urethral membrane • PUVs lead to mechanical obstruction which
(COPUM). affect normal bladder emptying and this will
• Congenital obstructing posterior urethral lead to:
membrane (COPUM) was first proposed by – High intraluminal pressure
Dewan and Goh and was later supported by – Increases voiding pressures
histological studies by Baskin. – Maldevelopment of the kidneys, ureters
• This concept proposes that, instead of a true and urinary bladder
valve, a persistent oblique membrane is rup- – Renal maldevelopment:
tured by initial catheter placement and, sec- • Renal parenchymal dysplasia is com-
ondary to rupture, forms a valve like mon and may be related to maldevelop-
configuration. ment of the metanephric blastema
• Renal tubular function may be affected
by high pressures that result in poor uri-
19.3 Pathophysiology nary concentrating ability
• Diuresis secondary to high urinary
• Posterior urethral valve is known to be asso- production
ciated with significant morbidity which is • This high urinary production will lead
not merely limited to transient urethral to ureteral and bladder dysfunction
obstruction. – Renal deterioration may also occur due to
• The congenital obstruction of the urinary tract hyperfiltration injury that causes:
at a critical time in organogenesis may pro- • Glomerulosclerosis
foundly affect lifelong kidney, ureteral, and • Chronic pyelonephritis associated with
bladder function as follows: vesicoureteral reflux
– Outflow obstruction leads to increased col- • Urinary stasis
lagen deposition and muscle hypertrophy • Incomplete bladder emptying
of the urinary bladder which can signifi- – These will also cause further insult to the
cantly thicken the bladder wall. developing kidneys.
• Hydronephrosis is common in these patients normally. These protective mechanisms

for several reasons: include:
– Bladder dysfunction with high back pres- – Massive unilateral vesicoureteral reflux.
sures on the ureter. – This is usually associated with an ipsilat-
– An abnormally deficient musculature of eral dysplastic kidney, known as vesicoure-
the ureter due to chronic distention from teral reflux and dysplasia syndrome.
high pressure or high urine flow. – Development of bladder diverticula.
– High urinary flow due to the lack of urinary – Rupture of renal calyces and development
concentrating ability of the nephron can of urinary ascites.
dilate the kidneys and ureters. • As patients with PUV age, bladder decompen-
– Abnormalities of the vesicoureteral junc- sation may develop, resulting in detrusor fail-
tion, such as reflux or, rarely, ureterovesi- ure and increased bladder capacity.
cal obstruction. • Many boys with PUV as they grow older will
• Vesicoureteral reflux is present in one half of develop larger-than-expected bladder volumes
male patients with a posterior urethral valve possibly due to overproduction of urine caused
for the following reasons: by tubular dysfunction and an inability to con-
– Secondary to increased intravesical pres- centrate urine (nephrogenic diabetes
sure which overcomes the competence of insipidus).
the ureterovesical junction. • Bladder function may change at puberty,
– Secondary to abnormal ureteral orifice resulting in high-pressure, chronic retention
position resulting from abnormal ureteral and necessitating the need for lifelong bladder
bud development during embryogenesis. management.
• Bladder dysfunction in patients with PUV is • Symptoms of bladder dysfunction may persist
secondary to: into adulthood in up to one third of patients
– Alterations in collagen deposition. and include urinary incontinence in up to 15 %
– Alteration in the development of detrusor of adults with a history of PUV.
smooth muscle cells.
– Poor compliance or uninhibited contrac-
tion of the detrusor muscle and eventual 19.4 Classification
myogenic failure.
– In mild cases, incontinence may be present. • A PUV is a congenital obstruction caused by
– In severe cases, ongoing deterioration of an embryological malformation of the poste-
renal function occurs. rior urethra.
– Bladder dysfunction often improves over • Posterior urethral valves are usually fusion of
time after definitive treatment of the the plicae colliculi between the entrances of
obstruction. the seminal vesicles at the veromontanum,
– Persistence of bladder dysfunction increases and extend to the membranous urethra.
the risk of: • The verumontanum, or mountain ridge, is a
• Urinary tract infection distinctive landmark in the prostatic urethra
• Persistent hydronephrosis and it is important in the classification of pos-
• Vesicoureteral reflux terior valves.
• Incontinence • This malformation will result in urethral
– All of these diminish renal function obstruction.
further. • The significance of this obstruction depends
• Several protective mechanisms may develop on the secondary effects on:
in boys with a posterior urethral valve; these – The urinary bladder
may lower intraluminal pressures and allow – The ureters
at least one renal unit to develop more – The kidneys
• In 1919, H. H. Young was the first to classify • The reported incidence is 1 per 8,000–1 per
posterior urethral valves into three types as 25,000 live births.
follows: • PUVs are the cause of renal insufficiency in
– Type I: approximately 10–15 % of children undergo-
• This is the most common type. ing renal transplant.
• This type of obstruction is believed to result • Approximately one third of patients born with
from abnormal insertion and absorption of PUV progress to end stage renal disease
the most distal aspects of the Wolffian ducts (ESRD).
during bladder development. • PUVs are usually diagnosed before birth or at
• In the healthy male, the remnants of birth when a boy is evaluated for antenatal
these ducts are observed as the plicae hydronephrosis.
colliculi. • Before the era of prenatal ultrasonography,
• This type is believed to be due to ante- PUVs were discovered during evaluation of
rior fusing of the plicae colliculi, muco- urinary tract infection (UTI), voiding dysfunc-
sal fins extending from the bottom of the tion, or renal failure.
verumontanum distally along the pros- • In the pre-antenatal ultrasonography era, a late
tatic and membranous urethra. presentation of PUV was considered a good
– Type II: prognostic indicator suggestive of a lesser
• This is the least common variant. degree of obstruction.
• It is characterized by vertical or longitu- • Prenatal diagnosis
dinal folds between the verumontanum – The widespread use of antenatal ultraso-
and proximal prostatic urethra and blad- nography has made it possible to diagnose
der neck. more cases of posterior urethral valves
– Type III: antenatally.
• This is the second common variant. – Currently, the diagnosis of PUV is usually
• It is due to a disc of tissue distal to made early at birth when a boy is evaluated
verumontanum. for antenatally diagnosed hydronephrosis.
• These valves are observed as a mem- – It was estimated that 10 % of boys diag-
brane in the posterior urethra nosed with prenatal hydronephrosis had
• These are believed to originate from PUVs.
incomplete canalization between the – Patients who are not diagnosed by antena-
anterior and posterior urethra. tal ultrasound may present shortly after
• It is also theorized to be a developmen- birth with distended bladder and difficulty
tal anomaly of congenital urogenital to pass urine.
remnants in the bulbar urethra. – Despite widespread use of antenatal ultra-
• It has been suggested that obstructions in the sonography, some patients with PUVs do
posterior urethra are more appropriately present later in life.
termed congenital obstructions of the poste- • Delayed presentation
rior urethral membrane (COPUMs). – PUVs manifest as a spectrum of disease
• The congenital urothelial remnants of type III severity.
posterior urethral valves have been eponymously – The delayed clinical presentation of PUVs
referred to as Cobb’s collar or Moorman’s ring. include:
• Urinary tract infection
• Diurnal enuresis in boys older than
19.5 Clinical Features 5 years
• Secondary diurnal enuresis
• PUV is the most common cause of lower uri- • Voiding pain or dysfunction
nary tract obstruction in male neonates. • An abnormal urinary stream
– PUVs are sometimes discovered during • Currently, approximately 50–75 % of boys

evaluation of abdominal mass or renal with PUV will be suspected on prenatal
failure. ultrasound.
– Hydronephrosis or proteinuria found on • The prenatal ultrasound findings suggestive of
examination for unrelated conditions may PUV include:
be the first sign of PUVs. – A thick walled bladder
• Neonates born with severe posterior urethral – The ‘keyhole’ sign with a dilated bladder
valve may present with severe pulmonary dis- and posterior urethra
tress secondary to pulmonary hypoplasia due – Unilateral or bilateral hydroureteronephrosis
to oligohydramnios. Physical findings can – Echo bright kidneys
include the followings: – Oligohydramnios
– Poor fetal breathing movements • Postnatally, the patient must be stabilized
– Small chest cavity prior to any investigation.
– Abdominal mass (ascites) • Complete blood count
– Potter facies • Serum electrolytes, BUN and creatinine.
– Limb deformities (skin dimpling) – To be accurate and to avoid maternal pla-
– Indentation of the knees and elbows due to cental effect, these should be checked at
compression within the uterus least 24 h after birth.
• In older children, physical findings can – The newborn is unable to concentrate
include: urine because of renal immaturity at
– Poor growth birth.
– Hypertension – This defect is exacerbated by renal dyspla-
– Lethargy sia such as that found with posterior ure-
– A large lower abdominal mass representing thral valves and if the renal dysplasia is
a markedly distended urinary bladder significant, the serum creatinine fails to
• A smaller number of patients with PUV will reach a normal level during the first year of
present late and their clinical presentation life.
include: – Serum creatinine levels >0.8 mg/dL during
– Diurnal enuresis the first year of life have been demonstrated
– Dribbling or poor urine stream to be associated with poor long-term renal
– Urinary tract infection function.
– Hematuria – This is considered a negative prognostic
indicator.
• Plain abdominal radiographs do not add to
19.6 Investigations and Diagnosis the actual diagnosis of posterior urethral
valves but may show the ground-glass
• With routine use of obstetric ultrasonography appearance seen in those with urinary
the prenatal diagnosis of posterior urethral ascites.
valve is becoming increasingly common. • Chest radiographs may be useful in the evalu-
• The antenatal ultrasound demonstrates signifi- ation of pulmonary hypoplasia.
cant hydronephrosis with possible renal corti- • Renal and bladder ultrasonography
cal thinning. The kidney is larger than – Postnatal renal ultrasonography is the ini-
expected for the patient’s gestational age. The tial investigation to be done in those with
hydronephrosis may be bilateral and both kid- suspected posterior urethral valve.
neys may be affected. – This is important as an initial noninvasive
• As a result of the routine use of antenatal and devoid of radiation investigation.
ultrasound, the number of cases of PUV diag- – Ultrasonography is helpful but not diag-
nosed prenatally has increased. nostic (Figs. 19.2, 19.3, and 19.4).
Figs. 19.2, 19.3, and 19.4 Abdominal ultrasound showing an atrophic dysplastic kidney seen in a patient with poste-
rior urethral valve and vesicoureteric reflux
– Features suggestive of posterior urethral urethra has been described as having a

valves are: keyhole appearance.
• Unilateral or bilateral hydronephrosis • Urinary ascites or perinephric collec-
• Enlarged kidneys with thinning of the tions due to urinomas may also be seen,
renal cortex most commonly soon after birth, and are
• In those with renal dysplasia, the renal caused by rupture of the urinary tract,
parenchyma is typically hyperechogenic typically at the level of the calyces.
with visible small cysts (<10 mm), but in • Voiding cystourethrogram (VCUG) (Figs. 19.5,
the most mildly affected cases, renal ultra- 19.6, 19.7, 19.8, 19.9, 19.10, and 19.11):
sonographic findings may be normal. – This is more specific for the diagnosis of
• A thickened bladder wall with trabecu- posterior urethral valve.
lations, and bladder diverticula – This should be performed under fluoros-
• The bladder may be of large or small vol- copy, with imaging of the posterior urethra,
ume, but it is invariably thick-walled. especially during the voiding phase.
• A dilated posterior urethra – PUV on voiding cystourethrogram is char-
• Echogenic lines that are the actual valve acterized by an abrupt tapering of urethral
leaflets might be seen. caliber near the verumontanum, with the
• The combination of the dilated, thick- specific level depending on the develop-
walled bladder and dilated posterior mental variant.
NO VESICOURETERIC REFLUX DILATED POSTERIOR URETHRA
Figs. 19.5 and 19.6 A micturating cystourethrogram showing posterior urethral valve. Note the dilated posterior ure-
thra. Note also the dilated thickened urinary bladder. Note also the absence of vesicoureteric reflux

posterior urethral valve.
Note the dilated posterior
urethra and the small
DILATED THICKENED
anterior urethra. Note also URINARY BLADDE
the dilated thickened
urinary bladder
DILATED POSTERIOR
URETHRA
SMALL ANTERIOR
URETHRA
– The diagnosis of PUV is indicated by the • Visualization of the valve leaflets

following features: • The posterior urethral valve is seen as a
• A thickened trabeculated bladder nonopacified line that separates the
• A dilated or elongated posterior urethra dilated posterior urethra from the nor-
• The bladder neck is typically hypertro- mal-caliber distal urethra
phic, leading to a lucent ring or collar • The findings of bladder diverticula
Fig. 19.8 A
micturating
cystourethrogram
showing posterior HYDRONEPHROSIS
urethral valve. Note the
dilated posterior urethra
and the small anterior
SEVERE
urethra. Note also the
VESICOURETERIC
dilated thickened REFLUX
urinary bladder and
severe unilateral DILATED THICKENED
vesicoureteric reflux URINARY BLADDER
HYPERTROPHIC
BLADDER NECK
DILATED POSTERIOR
URETHRA
SMALL ANTERIOR
URETHRA
Fig. 19.9 A
micturating
cystourethrogram
showing posterior
urethral valve. Note the
dilated posterior urethra
and the dilated
thickened urinary DILATED THICKENED
bladder. Note also the URINARY BLADDE
absence of
vesicoureteric reflux
DILATED POSTERIOR
URETHRA
• Vesicoureteral reflux is also seen in over • Intravenous urography (IVU):

50 % of cases. This can be unilateral or – IVU is not routinely used in children with
bilateral posterior urethral valve.
• Reflux into the ejaculatory ducts sec- – The contrast agent is poorly concentrated
ondary to elevated bladder and urethral and visualized in newborn kidneys, partic-
pressures may also be seen. ularly if renal function is diminished.
• The anterior urethra is typically smaller, – Elevated serum creatinine levels may pre-
under filled, and voiding is incomplete clude the use of IV contrast material.
• If the VUR has been high grade and uni- – IVU may show:
lateral, a “pop-off” may have allowed • An absent kidney in the case of renal
selective dissipation of back pressure, dysplasia or delayed renal function with
resulting from urethral obstruction. persistent high intraluminal pressures.
Fig. 19.10 A
micturating
cystourethrogram
showing posterior
urethral valve. Note the SEVERE VESICOURETERIC
dilated posterior urethra REFLUX
and the dilated
thickened urinary
bladder. Note also the
small anterior urethra
and unilateral
DILATED THICKENED
vesicoureteric reflux
URINARY BLADDE
DILATED POSTERIOR URETHRA
SMALL ANTERIOR URETHRA
• Hydroureteronephrosis may be seen. – The disease has occurred in patients with

• Delayed images may show bladder or moderate to end-stage renal disease after
urethral pathology, but the lower urinary being given a gadolinium-based contrast
tract is better visualized with VCUG. agent to enhance MRI or MRA scans.
• Computed Tomography: – NSF/NFD is characterized by:
– This is rarely necessary for the diagnosis of • Red or dark patches on the skin
posterior urethral valves. • Burning, itching, swelling, hardening,
– Elevated serum creatinine levels generally and tightening of the skin
preclude use of IV contrast material. • Yellow spots on the whites of the eyes
– CT scans with IV contrast enhancement • Joint stiffness with trouble moving or
may reveal: straightening the arms, hands, legs, or feet
• Dysplastic and/or dilated kidneys • Pain deep in the hip bones or ribs
• Delayed renal function and excretion • Muscle weakness
• Hydroureter • Sometimes it is fatal
• Dilated bladder with wall thickening, • Nuclear Imaging:
trabeculation, and diverticula – Nuclear cystography is useful to define the
• A dilated posterior urethra might be presence of vesicoureteral reflux but it is
seen not useful to define the extent or degree of
• Magnetic Resonance Imaging: reflux.
– Magnetic resonance imaging (MRI) is – Renal scintigraphy can determine the rela-
rarely used to diagnose posterior urethral tive renal function.
valve – The bladder should be drained prior to the
– The findings are similar to those of CT study to eliminate the effect of a distended,
scanning high-pressure bladder on renal function
– Gadolinium-based contrast agents used in and drainage.
MRI have been linked to the development – The presence of a much thickened hyper-
of nephrogenic systemic fibrosis (NSF) or trophied bladder wall may lead to second-
nephrogenic fibrosing dermopathy (NFD). ary ureterovesical junction obstruction.
19.7 Management 433
Figs. 19.11 and 19.12 Micturating cystourethrograms showing severe bilateral reflux
– Tc-dimercaptosuccinic acid (DMSA), glu- • Cystourethroscopy may be required to for-

coheptonate, and mercaptoacetyltriglycine mally confirm the diagnosis of posterior
(MAG-3) renal scintigraphy provide infor- urethral valves at the time of intervention (Fig.
mation about relative renal function. 19.12).
– The presence of photopenic areas within
the kidney indicate scarring or dysplasia.
– An absent or dysplastic kidney is seen as a 19.7 Management
photopenic area in the renal fossa
– The MAG-3 renal scan with furosemide • The management of patients with posterior
(Lasix) provides information about renal urethral valve requires a multidisciplinary
drainage and possible obstruction. team including:
• Urodynamic studies: – Pediatric urologists
– These provide information about bladder – Pediatric pulmonologists
storage and emptying. – A general pediatrician
– The term “valve bladder” is used to – Pediatric nephrologist
describe patients with PUV and a fibrotic – Neonatologists
noncompliant bladder. These patients are at – Radiologists
risk of developing: – The family
• Hydroureteronephrosis • The aims should be:
• Progressive renal deterioration – To treat pulmonary distress if present
• Recurrent infections – To relief urethral obstruction by passing a
• Urinary incontinence small size 5 F feeding tube
– Patients with PUV require periodic urody- – Fluid and electrolytes management
namic testing throughout childhood – Valve disruption
because bladder compliance may further – Treatment of bladder dysfunction and renal
deteriorate over time. insufficiency
• Treatment of the lower urinary tract may influ- – Fetal surgery is a high risk procedure reserved
ence progression of upper tract disease. for cases with severe oligohydramnios.
• Few patients with PUV present with bilateral – This will allow:
renal dysplasia at birth. Currently, these • Improved survival
patients can be treated successfully with peri- • Preservation of renal function
toneal dialysis and subsequently at around • Reduction in the respiratory compromise
1 year of age with renal transplantation. and limb abnormalities seen in associa-
• Approximately one third of patients with PUV tion with severe oligohydramnios.
progress to ESRD and these patients are – The specific procedures for in utero inter-
treated with dialysis and subsequently renal vention include:
transplantation. • Infusions of amniotic fluid
• Growth in these children may be significantly • Serial bladder aspiration (Serial
retarded and below the reference range for the vesicocentesis)
child’s age. • A vesicoamniotic shunt.
• These patients should have a balanced caloric – The risks of fetal surgery are significant
and protein intake to avoid an accelerated rise and include limb entrapment, abdominal
in serum creatinine levels. injury, and fetal or maternal death.
• Renal dysfunction and progression of ESRD • Treatment of posterior urethral valve is by
can be accelerated by: endoscopic valve ablation.
– Increased metabolic workload on the kid- • There are three specific endoscopic treatments
neys as seen at puberty of posterior urethral valves:
– Recurrent infections – Vesicostomy followed by valve ablation.
– Elevated bladder pressures – Pyelostomy followed by valve ablation.
– Increased caloric and protein intake – Primary (transurethral) valve ablation.
• Prenatal Intervention: • Currently, the standard treatment of posterior
– There remains no clinical consensus about urethral valve is primary (transurethral) abla-
the efficacy and use of prenatal intervention. tion of the valves.
– It was shown that there is a link between urine • Urinary diversion is rarely used and only used
outflow impairment and renal dysplasia. in selected cases.
– Lung hypoplasia is seen in patients with • Postoperatively, patients with posterior ure-
PUVs in association with oligohydramnios. thral valve should have regular and long term
– Currently, it is difficult to identify fetuses follow-up.
with PUVs who may benefit from prenatal • Neonatal Management:
intervention. – A size 6 Fr urethral catheter or feeding tube
– At the present time, there is no single should be passed to drain the bladder and
marker or combination of fetal urine mark- antibiotic prophylaxis should be started
ers that is reliable in identifying fetuses (e.g. trimethoprim 2 mg/kg).
with PUVs who may benefit from prenatal – In those neonates where it is not possible to
intervention. pass a catheter, a supra-pubic catheter
– Gestational age at diagnosis (<24 weeks) should be inserted.
and oligohydramnios have been found to – These patients should be followed up
be significant predictors of a worse renal closely including urine output and electro-
outcome. lyte measurements.
– The aim of prenatal intervention in those with – These patients may develop polyuria and/
PUVs is to decompress the fetal renal tract. or abnormalities of sodium, potassium
– This limit the associated lung underdevel- and bicarbonate as a result of excessive
opment, or pulmonary hypoplasia, that is renal losses secondary to post-obstructive
seen at birth in these patients. diuresis.
19.7 Management 435
– Creatinine level should be monitored daily – These children may be managed with a
till they normalize. transurethral or supra-pubic catheter until
– In boys born with a history of oligohy- such time as they are big enough for the
dramnios and significant pulmonary hypo- procedure.
plasia the priority of management is – As a guide, a body weight of 2.5 kg should
respiratory support and bladder drainage. allow safe and accurate PUV resection
Either a urethral or supra-pubic catheter is with standard endoscopic instruments.
sufficient to optimize urinary drainage – An alternative technique for small neonates
whilst awaiting respiratory stability. and to avoid the complications associated
– Neonates and infants who were not sus- with urethral or suprapubic catheters, a
pected to have PUV prenatally may present vesicostomy is constructed to ensure ade-
with: quate and continuous bladder drainage.
• Urosepsis – It is recommended that all boys have a fol-
• Obstructive voiding symptoms low-up cystoscopy within 3 months of the
• A distended bladder primary procedure to ensure completeness
• Palpable kidneys of valve ablation.
• Primary Valve Resection: – Others advocate a repeat MCUG within
– The procedure of choice for PUV is pri- 3 months of the primary procedure and
mary valve ablation. proceed to cystoscopy only if the MCUG
– This should be performed once the baby is suggests persisting urethral obstruction.
stable. • Cystoscopy:
– The patient should be covered with – Cystoscopy is important to confirm the
antibiotics. diagnosis of PUV
– A diagnostic cystoscopy using 0° 6/8 Fr – Therapeutic cystoscopy (i.e., transurethral
neonatal cystoscope is performed. incision of the PUVs):
– The diagnosis of PUV is confirmed. • Multiple techniques have been described
– The configuration of the bladder neck and for ablating the valves.
appearances of the bladder and ureteric ori- • Currently, PUVs are disrupted under
fices should also be noted. direct vision by cystoscopy using an
– A resectoscope is used to resect the valve endoscopic loop, Bugbee electrocauteri-
with either the cold/sickle blade or bugbee zation, or laser fulguration.
electrode. • In extremely small infants (<2,000 g), a
– Valve resection is typically performed at 2 F Fogarty catheter may be passed
the 5, 7 and 12 o’clock positions. either under fluoroscopic or direct
– A urethral catheter is placed at the end of vision for valve disruption.
the procedure and removed 24–48 h later. • It is important to perform valve disrup-
– Complications of primary valve ablation tion in the least traumatic way to avoid
include: secondary urethral stricture or injury to
• Bleeding the urethral sphincter mechanism.
• Incomplete valve resection • A temporary vesicostomy may be per-
• Urethral stricture formed in small infants with small ure-
• Inadvertent damage to the external thra that does not admit available
sphincter cystoscopic instruments.
– For preterm or very small neonates, endo- • Bladder management:
scopic resection is delayed due to the diffi- – Place a 5 F or 6 F urethral catheter to allow
culties of the small caliber of the urethra for bladder drainage.
and potential complications of using the – Cystoscopic valve fulguration can be per-
relatively larger instruments. formed within the first few days of life.
– A vesicostomy can be performed as a tem- – Postnatal primary valve ablation:

porary solution in those with a small ure- • Transurethral incision of the PUV dur-
thra that can not accommodate the ing the first few days of life is the pre-
instrument. ferred treatment.
– Cutaneous ureterostomies are rarely per- • The valves can be incised at the 12-, 5-,
formed and reserved for those with second- and 7-o’clock positions, with either a
ary ureterovesical junction obstruction cold knife or electrocautery.
from bladder hypertrophy. • Some surgeons prefer to leave a catheter
– Severe or prolonged urethral obstruction in place for 2–3 days after the
can lead to a fibrotic, poorly compliant procedure.
bladder. This is secondary to increased • Approximately two thirds of patients
bladder collagen deposition and detrusor have successful valve ablation with one
muscle hypertrophy and hyperplasia. This procedure.
will led to: • One third of patients require a second
• Poor compliance of the urinary bladder incision.
• Elevated urinary bladder storage • Because approximately one third of
pressures patients will require a second valve inci-
• Increased risk of vesicoureteric reflux sion, some authors recommend routine
• Increased risk for hydroureteronephrosis surveillance cystoscopy 1–2 months
• Increased risk of urinary incontinence after initial incision to evaluate and treat
– The use of urodynamic testing to assess any residual valve.
bladder compliance help identify patients • The timing of the postoperative VCUG
at risk. varies and ranges from several days to
– Some of these patients may respond to several months.
anticholinergic medication, such as – Vesicostomy:
oxybutynin. • This is reserved for patients with small
– The use of clean intermittent catheteriza- urethral size that cannot accommodated
tion (CIC) may help some of these patients the available instruments.
to achieve continence by preventing the • This allows free bladder drainage.
bladder from overfilling. • It is important to create an adequate
– In patients who do not gain adequate blad- stoma as a large vesicostomy may be
der capacity and safe compliance despite complicated by bladder prolapse
optimal medical management, augmenta- while a small stoma may result in sto-
tion cystoplasty may be required. mal stenosis and inadequate bladder
• Surgical treatment: emptying.
– The surgical treatment of patients with – Cutaneous ureterostomies:
PUVs varies according to age, bladder sta- • Bilateral cutaneous ureterostomies can
tus, and renal status. be performed to provide for urinary
– Prenatal surgery has been reported in drainage.
patients diagnosed with PUV with the goal • Techniques for cutaneous ureterostomy
of improving postnatal outcomes. include:
– Antenatal intervention with vesicoamniotic – End stomal ureterostomy
shunting would improve postnatal renal – Loop ureterostomy
function. – Y-ureterostomy (in which the ureter
– However, identification of those patients is divided and one end is brought to
who may benefit from this early interven- the skin and the other is reanasto-
tion remains unclear and because of this mosed in a uretero-ureterostomy)
prenatal intervention remains limited. – Ring ureterostomy
19.8 Medications Used in Patients with PUV 437
• Potential complications of cutaneous • The procedure involves placement of a

ureterostomies include: nonrefluxing tubular conduit for cathe-
– Ureteral devascularization terization between the bladder and skin
– Inadequate drainage to provide an alternative channel for
– Stomal stenosis catheterization.
• Secondary bladder surgery: • This is also called the Mitrofanoff
– Augmentation cystoplasty: technique
• Indications for bladder augmentation • The catheterizable tubular conduit can
include: be formed from:
– Inadequately low bladder storage vol- – The appendix
umes and high bladder pressures – The ureter
despite anticholinergic medication – Tubularized bowel
and clean intermittent catheterization. • The stoma often can be hidden in the
– Augmentation cystoplasty can significantly umbilicus to provide acceptable
improve patient lifestyle in those who have cosmesis.
intractable incontinence due to poor com- • Some patients with PUV:
pliance and bladder overactivity. – Continue to suffer from urinary tract
– By lowering intravesical pressures, the infection
upper urinary tract may also be protected. – Their renal function remains fragile or
– The ileum is most commonly used; how- deteriorates
ever, large bowel, stomach, and ureter are – Have a significant deterioration in the
also used. appearance of the upper tracts
– Augmentation should only be offered to – Their bladder emptying is incomplete
patients willing to commit to lifelong inter- • The aim in these children should be to maxi-
mittent catheterization. mize their renal potential and to delay or avoid
– Potential complications include: renal replacement.
• Bladder rupture (approximately 10 % of • These patients can be managed by early uri-
patients) nary diversion, either by vesicostomy or bilat-
• Electrolyte disturbances, which may be eral ureterostomy or pyelostomy. This aims to
worsened by the placement of intestinal protect the upper urinary tracts and minimize
mucosa in contact with urine, especially the risks of infection.
in those with a serum creatinine greater • A recent development is the use of a refluxing
than 2 mg/dL. ureterostomy as a form of urinary diversion.
• Mucus production, which can be a The refluxing ureterostomy is particularly
source of catheter blockage and may be useful in boys with fragile renal function. This
a nidus for stone formation. technique will minimize the potential harmful
• The future risk of neoplasia has not yet effects of the high-pressure bladder that is
been defined in these patients, but sev- present in the early period following valve
eral cases of malignant degeneration in ablation.
augmented bladder have been reported.
– Continent appendicovesicostomy:
• In children with PUVs, institution of
clean intermittent catheterization 19.8 Medications Used in Patients
through the sensitive urethra can be with PUV
difficult.
• In addition, some patients may have a • The primary medications involved in bladder
much dilated proximal urethra which management are anticholinergic medications
may not be easily catheterized. used to improve bladder compliance.
• Other medications that may be needed include • These patients need periodic radiologic and
prophylactic antibiotics and medications used urodynamic evaluation to monitor the upper
in the management of renal insufficiency. urinary tract and bladder changes to determine
– Anticholinergic medications are used to bladder capacity, compliance, and post void
improve bladder capacity and compliance residual urine volumes.
in the patient with elevated detrusor pres- • They should have periodic renal sonography
sures, which may cause hydronephrosis, and serum creatinine levels.
UTI, or incontinence. • Urinary incontinence: Approximately one
– Early use of anticholinergic medications third of patients with PUVs have problems
has been associated with improved bladder with diurnal enuresis when older than 5 years.
function in infants with high voiding pres- Diurnal enuresis may be caused by the bladder
sures and low storage volumes. changes that lead to elevated storage pressures
– Oxybutynin chloride (Ditropan) inhibit the and poor emptying.
muscarinic action of acetylcholine on • Rarely, sphincteric dysfunction secondary to
smooth muscle and exerts an antispas- valve ablation can be present. Treatment includes:
modic effect on bladder smooth muscle – Anticholinergic medications
(anticholinergic action) leading to its – Clean Intermittent Catheterization (CIC)
relaxation. – In some patients, bladder augmentation
– Hyoscyamine sulfate (Levbid, Levsin) • Pulmonary hypoplasia secondary to intrauter-
inhibit the postganglionic cholinergic ine renal dysfunction and oligohydramnios is
receptors on smooth muscle cells. the primary cause of death.
– Tolterodine (Detrol) is a new more selec- • Other complications of PUV are generally
tive antimuscarinic drug targeted for detru- secondary to chronic bladder changes, leading
sor smooth muscle. to elevated detrusor pressures which
– Antibiotics subsequently lead to progressive renal dam-
• Patients with history of recurrent UTI may age, infection, and incontinence.
benefit from antibiotic prophylaxis, especially • Renal insufficiency and end stage renal dis-
in the presence of vesicoureteral reflux. ease is expected in those with severe posterior
– Prophylactic dosage is usually one quarter urethral valve.
of the therapeutic dose administered once – Approximately 25 % of those with PUVs
per day. die of renal insufficiency in the first year of
– More appropriate antibiotics in children life
include trimethoprim (TMP), sulfamethoxa- – Approximately 25 % of those with PUVs
zole (SMZ), nitrofurantoin, and amoxicillin. die later in childhood
– Trimethoprim and sulfamethoxazole – Approximately 50 % survive to adulthood
(Bactrim, Septra, Cotrim) alone or in com- with varying degrees of renal function
bination with SMZ is the most commonly – Today, with good follow-up, early diagno-
used antibiotic for both treatment and pro- sis and treatment, and advent of better tech-
phylaxis of UTI. niques in the treatment of pediatric renal
insufficiency, most of these children can be
expected to survive. This also include early
19.9 Prognosis and Follow-Up diagnosis and aggressive treatment of
infections and bladder dysfunction.
• PUV is a lifelong condition that requires con- • There are several risk factors for progression
tinued medical management. of PUV related complications which include:
• Subsequent renal deterioration and bladder – Elevated nadir creatinine defined as greater
changes can be treated and minimized with than 1 mg/dL measured during the first
adequate follow-up care. year of life.
19.10 Long-Term Outcomes 439
– Bladder dysfunction with poor compliance • Today, the mortality of patients with PUVs is
– Elevated leak point pressures less than 3 %. This is attributed to several fac-
– The need for clean intermittent catheterization tors including:
• Vesicoureteral reflux: – Early prenatal diagnosis
– Vesicoureteral reflux is commonly associ- – Prompt resolution of bladder obstruction
ated with PUVs and is present in as many – Aggressive treatment of bladder dysfunction
as one third of patients. – Improved surgical techniques
– Vesicoureteral reflux is generally second- – Improved dialysis and transplantation
ary to elevated intravesical pressures. techniques
– Therefore, the treatment of vesicoureteral • Approximately one third of patients with
reflux in patients with PUVs involves treat- PUVs progress to renal insufficiency in their
ment of intravesical pressures using: lifetimes.
• Anticholinergics • An interesting group of patients are those with
• Timed voiding vesicoureteral reflux dysplasia (VURD)
• Double voiding syndrome.
• Clean intermittent catheterization – In these patients, one kidney is hydrone-
• Bladder augmentation phrotic, nonfunctioning, and has high-
• Urinary tract infections: grade vesicoureteral reflux.
– Recurrent UTIs are common in patients – The high-grade reflux is thought to act as a
with PUV. pop-off valve, leading to reduced overall
– This is predisposed to by several factors: bladder pressures and preservation of con-
• Elevated intravesical pressures predis- tralateral renal function.
pose these patients to infection, possibly – In the past, these patients were thought to
by altering urothelial blood flow. have a better outcome due to preserved
• Elevated post void residual urine vol- renal function in one kidney at the sacrifice
umes, leading to stasis of urine. of the other.
• Dilated upper urinary tracts, with or – These patients however, may suffer long-
without vesicoureteral reflux. term adverse renal function with hyperten-
– The management and prevention of UTIs sion, proteinuria, and renal failure.
include:
• Lowering bladder pressures by anticho-
linergic medications 19.10 Long-Term Outcomes
• Lowering post void residual urine volume
via clean intermittent catheterization • The presence of bladder outflow obstruction
• Administering prophylactic antibiotics as a result of PUV will result in an increase in
• Urinary incontinence: the intravesical pressure.
– It is important to follow these patients with • This raised intraluminal pressure will be trans-
urodynamic studies. mitted to the developing kidney leading to:
– To improve urinary continence, it is impor- – Renal parenchymal apoptosis
tant to: – Abnormal cellular differentiation
• Lower bladder pressure – Glomerular changes
• Improve bladder compliance • The extent of these early changes will deter-
• Minimize post void residual urine mine the renal function in later life.
volume • The degree of obstruction is important in this
• In some, bladder augmentation may be regard.
needed • In cases where the obstruction is less severe or
• Over the last 30 years, the prognosis of chil- declares itself later in pregnancy, the effects of
dren with PUV has steadily improved. obstruction tend to be more on the bladder and
renal effects are limited to dilatation of the 25–50 % of cases, and this improvement is
collecting system with minimal disruption of more likely in those presenting as neonates or
normal nephrogenesis. during infancy.
• An alternative theory propose that renal dys- • Persistent VUR, especially high grade and
plasia seen in conjunction with posterior ure- bilateral, after successful valve ablation is
thral valves is secondary to abnormal position associated with poor long-term renal
of the ureteric bud and implantation into the outcome.
metanephric blastema. • Anti-reflux procedures in boys with PUV is no
• Renal dysfunction seen in patients with longer recommended as this is associated with
posterior urethral valve appears to be the a high failure rate.
result of varying degrees of inherent dys- • Patients with high grade VUR and poor func-
plasia and the effects of bladder outflow tion of the ipsilateral kidney are treated with
obstruction. nephrectomy of the non-functioning ipsilat-
• In post-natal life these changes can be further eral kidney and bladder augmentation using
exaggerated by: the dilated ureter.
– Urinary tract infections • A refluxing ureterostomy as a form of urinary
– VUR diversion can be used also.
– Bladder dysfunction • The distal ureter has been used as a Mitrofanoff
• A significant loss of nephrons will lead to channel with or without an associated anti-
hyperfiltration of existing functional nephrons reflux procedure.
as a result of vasodilatation of the afferent arte- • Persistent high grade VUR are treated surgi-
rioles (glomerular capillary hypertension). cally prior to renal transplant. These are
• This compensatory mechanism will decom- known to be risk factor for recurrent urinary
pensates over time. tract infection which has a negative impact on
• The end result is: a transplanted kidney.
– Glomerulosclerosis
– Proteinuria
– Hypertension 19.10.2 Hydro-ureteronephrosis
– Reduced glomerular filtration rate
– Damage to the distal nephron impairs the • The majority of neonates presenting with pos-
concentrating ability of the kidney result- terior urethral valves will have bilateral
ing in polyuria and polydipsia (nephro- hydro-ureteronephrosis.
genic diabetes insipidus) • Some of these cases will worsen as a result
– End stage renal failure of functional obstruction at the level of
uretro-vesical junction which usually
resolves within 48–72 h. This is attributed to
19.10.1 Vesico-ureteric Reflux the thickened trabeculated bladder wall that
collapses, pinching off the ureteric orifices
• At presentation, approximately 50 % of following decompression of the urinary
patients with PUV have vesico-ureteric reflux bladder. The obstruction is usually followed
(VUR) on the initial MCUG. by post-obstructive diuresis and do not
• VUR in these patients is secondary to the require internal JJ stenting or placement of
bladder outflow obstruction and co-existent nephrostomies.
bladder dysfunction. • Other cases of hydro-ureteronephrosis may
• Approximately 15 % of patients with PUV improve following catheterization.
will have unilateral high grade VUR with ipsi- • Ureteric re-implantation with or without
lateral non-functioning kidney. tapering is no longer performed in cases
• Following valve ablation the severity of VUR of hydro-ureteronephrosis secondary to
may decrease or resolve completely in PUV.
19.10 Long-Term Outcomes 441
19.10.3 Bladder Dysfunction • These patients will need renal transplantation.

• Urinary bladder assessment is an important
• The importance of bladder dysfunction and its part of the pre-transplant work-up of these
impact outcome on both urinary continence patients.
and renal function in boys with posterior ure- • A high pressure, poorly compliant, low blad-
thral valves was recognized. der capacity may risk the transplanted kidney
• This is secondary to in-utero changes in with the possibility of graft loss.
response to outflow obstruction and/or the • These patients are managed with bladder aug-
result of urinary diversion. mentation which can be performed prior to or
• Others believe that urinary diversion does not after renal transplantation.
adversely affect the bladder function but may – Bladder augmentation cystoplasty with/
improve it. without a catheterisable conduit performed
• The ‘valve bladder syndrome’: prior to renal transplant allows post-
– This was introduced to encompass several fea- operative healing without immuno-
tures seen in patients with PUV and include: suppression but risks a ‘dry cystoplasty’
• The abnormal voiding patterns and which must be managed by bladder cycling
symptoms of voiding dysfunction and lavages.
• The persistent thick walled bladder – Bladder augmentation cystoplasty can be
• Incomplete bladder emptying performed after renal transplantation and
• Associated upper urinary tract dilatation in these, it is important that immuno-
– Three dominant urodynamic patterns were suppression requirements have been stabi-
found in these patients: lized and the improved renal function
• The hyper-reflexic bladder offers clear advantages. The transplanted
• The hypo-compliant bladder ureter may be reimplanted into the native
• The acontractile bladder bladder or brought out as a cutaneous
• Overlap between these patterns may be ureterostomy.
seen – The 5 year renal graft survival rates in the
• Urodynamic abnormalities were observed in PUV have improved over the last two
80 % of the overall patient group with PUVs. decades from 40 % in the 1980s to near
• Bladder dysfunction is an important key to 70 % in the 1990s.
long term renal function outcomes.
• Bladder instability and poor compliance cor-
relate with a poor renal functional outcome. 19.10.5 Fertility
• It was shown that patients with the following
features are more likely to progress to end • The following factors influence the efficacy of
stage renal disease: ejaculation in patients with posterior urethral
– Severe bladder dysfunction, defined as low valves:
compliance with end filling pressure >40 cm – Persisting dilatation of the posterior
of H2O urethra
– Post-void residual volume >30 % – Damage to tissues around the
– Underactive detrusor verumontanum
– Patients in need for clean intermittent cath- – Secondary urethral strictures resulting
eterization (CIC) from previous surgery
• Erectile dysfunction is seen more commonly
in patients with chronic kidney disease and
19.10.4 Renal Transplantation those on dialysis.
• The majority of these patients however, will
• A significant number of boys with PUV prog- have a semen analysis that is considered
ress to end-stage renal failure. within the normal range.
Further Reading 13. Heikkila J, Holmberg C, Kyllonen L, Rintala R, et al.

Long term risk of end stage renal disease in patients with
posterior urethral valves. J Urol. 2011;186:2392–6.
1. Ansari MS, Gulia A, Srivastava A, Kapoor R. Risk
14. Holmdahl G, Sillen U, Hanson E, Hermansson G,
factors for progression to end-stage renal disease in
et al. Bladder dysfunction in boys with posterior ure-
children with posterior urethral valves. J Pediatr Urol.
thral valves before and after puberty. J Urol. 1996;
2010;6(3):261–4.
155:694–8.
2. Bhadoo D, Bajpai M, Panda SS. Posterior urethral
15. Hoover DL, Duckett JJ. Posterior urethral valves, uni-
valve: prognostic factors and renal outcome. J Indian
lateral reflux and renal dysplasia: a syndrome. J Urol.
Assoc Pediatr Surg. 2014;19(3):133–7.
1982;128(5):994–7.
3. Capitanucci ML, Marciano A, Zaccara A, La Sala E,
16. Kitagawa H, Pringle KC, Koike J, Zuccullo J, et al.
Mosiello G, De Gennaro M. Long-term bladder func-
Vesicoamniotic shunt for complete urinary tract
tion followup in boys with posterior urethral valves:
obstruction is partially effective. J Pediatr Surg.
comparison of noninvasive vs invasive urodynamic
2006;41(2):394–402.
studies. J Urol. 2012;188:953–7.
17. Kousidis G, Thomas DFM, Morgan H, Haider N,
4. Casey JT, Hagerty JA, Maizels M, et al. Early admin-
et al. The long-term outcome of prenatally detected
istration of oxybutynin improves bladder function and
posterior urethral valves: 10 to 23 year follow-up
clinical outcome in newborns with posterior urethral
study. BJU Int. 2008;102:1020–4.
valves. J Urol. 2012;188:1516–20.
18. Lopez Pereira P, Espinosa L, Martinez Urrutina MJ,
5. Clark TJ, Martin WL, Divakaran TG, Whittle MJ,
Lobato R, et al. Posterior urethral valves: prognostic
et al. Prenatal bladder drainage in the management of
factors. BJU Int. 2003;91:687–90.
fetal lower urinary tract obstruction: a systematic
19. Nakamura S, Kawai S, Kubo T, Kihara T, Mori K,
review and meta-analysis. Obstet Gynecol. 2003;
Nakai H. Transurethral incision of congenital obstruc-
102(2):367–82.
tive lesions in the posterior urethra in boys and its
6. Cuckow PM, Dineen MD, Risdon RA, Ransley PG,
effect on urinary incontinence and urodynamic study.
et al. Longterm renal function in posterior urethral
BJU Int. 2011;107:1304–11.
valves, unilateral reflux and renal dysplasia syn-
20. Nanda M, Bawa M, Narasimhan KL. Mini-
drome. J Urol. 1997;158(3 pt 2):1004–7.
vesicostomy in the management of PUV after valve
7. De Gennaro M, Mosiello G, Capitanucci ML, Silveri M,
ablation. J Pediatr Urol. 2012;8:51–4.
et al. Early detection of bladder dysfunction following
21. Narasimhan KL, Mahajan JK, Kaur B, Mittal BR,
posterior urethral valves ablation. Eur J Pediatr Surg.
Bhattacharya A. The vesicoureteral reflux dysplasia
1996;6:163–5.
syndrome in patients with posterior urethral valves.
8. DeFoor W, Clark C, Jackson E, Reddy P, et al. Risk
J Urol. 2005;174(4 Pt 1):1433–5.
factors for end stage renal disease in children
22. Riley P, Marks SD, Desai D, Mushtaq I, et al.
with posterior urethral valves. J Urol. 2008;180:
Challenges facing renal transplantation in pediatric
1705–8.
patients with lower urinary tract dysfunction.
9. DeFoor W, Tackett L, Minevich E, McEnery P,
Transplantation. 2010;89(11):1299–307.
Kitchens D, Reeves D, et al. Successful renal trans-
23. Sarhan O, Zaccaria I, Macher M, Muller F, et al. Long-
plantation in children with posterior urethral valves.
term outcome of prenatally detected posterior urethral
J Urol. 2003;170(6 Pt 1):2402–4.
valves: a single centre study of 65 cases managed by
10. Dewan PA, Zappala SM, Ransley PG, Duffy PG.
primary valve ablation. J Urol. 2008;179(1):307–12.
Endoscopic reappraisal of the morphology of con-
24. Soliman SM. Primary ablation of posterior urethral
genital obstruction of the posterior urethra. J Urol.
valves in low birth weight neonates by a visually
1992;70:439–44.
guided Fogarty embolectomy catheter. J Urol.
11. Ghanem MA, Wolffenbuttel KP, de Vylder A, Nijman
2009;181(5):2284–9. discussion 2289–90.
RJM. Long-term bladder dysfunction and renal func-
25. Tikkinen KA, Heikkilä J, Rintala RJ, Tammela TL,
tion in boys with posterior urethral valves based on
Taskinen S. Lower urinary tract symptoms in adults
urodynamic findings. J Urol. 2004;171:2409–12.
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matched cohort study. J Urol. 2011;186(2):660–6.
Vesicostomy vs. Primary valve ablation of posterior
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Utricular Cyst (Prostatic Utricular
Cyst) 20
20.1 Introduction • They are variable in size but are usually small
in size (commonly <10 mm). They can how-
• The prostatic utricle is a small, epithelium- ever grow to reach a large size.
lined diverticulum of the prostatic urethra. • Morphologically, prostatic utricle cyst appears
• Utricle is derived from the Latin word as a small, single, smooth, unilocular cyst of
“pouch,” which forms a cul-de-sac. The pros- variable size.
tatic utricle (pouch of the prostate) is a small • The cyst lining can be:
diverticulum (6 mm long) in the prostatic ure- – Cuboidal
thra (Fig. 20.1). – Columnar
• It is located in the verumontanum (seminal – Squamous or transitional type
colliculus) between the two openings of the
ejaculatory ducts and extends backward and
slightly upward for a very short distance URINARY UTRICULAR CYST
within the medial lobe of the prostate. BLADDER
• It is also known as the vagina masculina or
vesicula prostatica.
• It is a normal anatomic variant representing
the remnant of the fused caudal ends of the
Müllerian ducts. This origin is occasionally
disputed.
• It is considered to represent the male homo-
logue of the female uterus and vagina.
• In 1905, Robert William Taylor stated the
function of the prostatic utricle thusly: “In
coitus it so contracts that it draws upon the
openings of the ejaculatory ducts, and thus
renders them so patulous that the semen read-
ily passes through.”
• Utricle cysts always arise from the level of the
verumontanum and are always in the midline.
• The cyst typically lies between the bladder
and the rectum and, thus, is palpable on per Fig. 20.1 A micturating cystogram showing a large
rectal exam in 50 % of the cases. utricular cyst

444 20 Utricular Cyst (Prostatic Utricular Cyst)
Figs. 20.2 and 20.3 Clinical photographs showing severe hypospadias. This is known to be associated with utricular
cyst. The increasing severity of the hypospadias correlates with increasing size of the utricle

photograph showing
Prune belly syndrome
which is known to be
associated with
utricular cyst
• Prostatic utricle cyst is usually seen during the – Anorectal agenesis

first to second decades of life, with a mean age – Down’s syndrome
range of 26 years. • Hypospadias is considered the most com-
• There is an association between utricular cysts monly associated malformation with the
and: prostatic utricle (14–47 %), and the increas-
– Renal agenesis/dysgenesis (10–25 %) ing severity of the hypospadias correlates
– Hypospadias (25 %) (Figs. 20.2 and 20.3) with increasing size of the utricle (Figs. 20.2
– Prune-belly syndrome (Fig. 20.4) and 20.3).
20.3 Classification of Utricular Cysts 445
• Normally, the prostatic utricle distends with the urogenital sinus caused by an error in the
urine during voiding and then passively production or sensitivity to local testosterone
drains. or anti-Mullerian hormone.
• Poor emptying leads to urine retention and • These cysts are differentiated anatomically
stasis and this leads to complications from Mullerian duct cysts.
including: – Utricular cysts:
– Recurrent urinary tract infection • Always in the midline
– Hematuria • They present during the first to second
– Urethral discharge decade of life
– Recurrent epididymitis • They communicate with the urethra
– Voiding dysfunction • They have a tubular or vesicular shape
– Urine retention • The majority are seen in younger patients
– Post voiding urine drippling • They have an association with unilat-
– Stone formation within the utricle cyst eral/bilateral renal agenesis, and
– Malignant transformation (e.g. clear cell hypospadias
carcinoma, or squamous cell carcinoma) • They can be visualized with a micturat-
with a reported prevalence as high as 3 %. ing cystourethrogram or a retrograde
• Utricular cyst is rare but along with its rarity, urethrogram.
it presents a challenge in its diagnosis and – Mullerian duct cysts:
proper management. Awareness of this is • Usually seen above the prostate
important. • They are seen in the older age group
• Persistence or untreated prostatic cyst could ranging from 2 to 75 years
be a cause of infertility. • Mullerian duct cysts generally do not
• The differential diagnoses include mullerian communicate with the urethra
duct cysts, bladder diverticulum, cystic • They cannot be visualized with a mic-
teratoma, seminal vesicle cyst, epididymal turating cystourethrogram or a retro-
cyst and Wolffian duct cyst. grade urethrogram.
• It is proposed that these cysts originate
due to failure of fusion of Mullerian
20.2 Embryology duct resulting from deficient Mullerian
inhibitory factor.
• Embryologically, in the male fetus the • They are associated with intersex
Mullerian ducts regress under the influence of conditions
anti-Mullerian hormone (Mullerian inhibiting • They are also seen in those with normal
substance). external genitalia
• This is a glycoprotein secreted by the Sertoli • Based on this, it has been postulated that
cells of the fetal testes at eight gestational the Mullerian duct cysts are the rem-
weeks. nants of the paramesonephric ducts
• Persistence of the Mullerian ducts as result of rather than the Mullerian ducts.
failure of synthesis or action of Mullerian
inhibitory substance results in persistent
Mullerian duct syndrome. 20.3 Classification of Utricular
• This is characterized by the presence of uter- Cysts
ine tissue and fallopian tubes in a phenotypic
and genotypic male. • Ikoma et al. in 1985 classified utricular cysts
• Utricular cysts are thought to result from into four types depending on the size of the
incomplete regression of the Mullerian ducts cyst and the site of communication with the
or incomplete androgen-mediated closure of urethra.
Figs. 20.5 and 20.6 Testicular ultrasound and Doppler ultrasound of a child with acute scrotum. Note the enlarged left
epididymis which was found to be secondary to a utricular cyst
• This classification was based on urethro- • A large prostatic utricle is more often
graphic configuration. associated with male hypospadias. This is
– Grade 0: The utricle opening is located on more commonly seen in those with proxi-
the posterior urethra but the utricle does not mal penile, penoscrotal and perineal
extend over the verumontanum. hypospadias.
– Grade I: The utricular cyst is larger than • This must be kept in mind as patients with a
grade 0 but the cyst does not reach the blad- large prostatic utricle, direct catheterization of
der neck. the bladder during surgical repair of hypospa-
– Grade II: The utricular cyst is more dias or during VCUG may be difficult
enlarged and its dome extends over the secondary to preferential passage of the cath-
bladder neck. eter into the utricle.
– Grade III: In grades 0, I, and II, the pros- • The clinical presentation of utricular cyst is
tatic utricle opens into the central area of variable and include (Figs. 20.5 and 20.6):
the verumontanum, but when the opening – Recurrent UTI
is situated in the bulbous urethra just distal – Recurrent epididymitis
to the external sphincter, this is classified as – Hematuria
grade III. – Pyuria
– Urinary incontinence
– Urine retention
20.4 Clinical Features – Post void urinary drippling
– Constipation
• Utricular cyst is a very rare congenital anom- – A pelvic mass
aly that arises from incomplete regression of – Suprapubic or rectal pain
the Mullerian ducts and commonly seen in • Rarely it may enlarge and present as an abnor-
males with perineal or penoscrotal hypospa- mal lower abdominal or pelvic mass.
dias and in intersex disorders. • When enlarged, it may be observed during
• Usually they are asymptomatic discovered pelvic or CT-scan as a fluid filled cavity
incidentally. between bladder and rectum.
• The presentation of utricular cysts is variable,
and because many are asymptomatic, they
escape detection. 20.5 Investigations
• A prostatic utricle cyst is usually small in size
and asymptomatic. • These patients should be investigated includ-
• A small prostatic utricle is occasionally seen ing abdominal and pelvic ultrasound and CT
as an incidental finding on routine VCUG as a scan as well as a micturating cystourethrogam
tiny diverticulum of a few millimeters in and or an ascending urethrogram.
length or on rare occasions measuring up to • Voiding cystourethrogram (VCUG) and retro-
1 cm. grade urethrography (RUG) can define the
20.6 Treatment 447
Figs. 20.7 and 20.8 A micturating cystourethrogram showing a large utricular cyst which is arising from the prostatic
urethra. Note the large size of the cyst and its location
utricle size, which usually ranges from a few

millimeters to more than 2 cm.
• VCUG is important to define the site of the
cyst and its relation to the urethra as well as its
size (Figs. 20.7 and 20.8).
• CT-scan will localize the site of the cyst, its
shape and size as well as its relation to the uri-
nary bladder and rectum (Figs. 20.9, 20.10,
and 20.11).
• MRI can easily identify these cysts by virtue
of their high signal on T2-weighted images
but this investigation is reserved for cases that
are difficult to diagnose by the more common
and simpler investigations.
20.6 Treatment
• Surgical excision is the treatment of choice for Figs. 20.9 and 20.10 CT-scans showing a large utricu-
symptomatic utricular cysts. lar cyst
accidentally excising both vas deference

because of their close proximity or more com-
monly insertion in the utricular cyst. The
importance of this need to be emphasizes and a
preoperative thorough discussion with the par-
ents in this regard is of paramount importance
(Figs. 20.12, 20.13, and 20.14).
• Surgical complications include:
– Incomplete excision
– Impotence
– Excision of one or both seminal vesicles
– Excision of one or both vas
Fig. 20.11 CT-scan showing a large utricular cyst
– Excision of portions of the prostate
– Rectal injury
• Surgical management of prostatic utricle cyst
remains challenging, because of the rarity of
this disorder and due to the close proximity of 20.7 The Müllerian Duct Cyst
these lesions to the ejaculatory ducts, pelvic
nerves, rectum, vas deferens and ureters. • The müllerian duct cyst is a remnant of the
• Surgical treatment should be reserved for caudal ends of the fused müllerian duct, a
symptomatic utricle cysts only. structure that typically regresses in utero.
• The definitive treatment of symptomatic utric- • These cysts are typically located in the midline,
ular cyst is surgical excision but the approach posterior to the bladder and above the prostate.
remains controversial. • Mullerian duct cysts generally do not commu-
• Several surgical approaches have been nicate with the urethra
described including: • Müllerian duct cysts do not communicate with
– Endoscopic transurethral cyst catheteriza- the prostatic urethra, but are connected to the
tion and aspiration verumontanum by a thin stalk.
– Cyst orifice dilatation • Unlike utricular cysts, the müllerian duct cyst
– Incision and deroofing is not typically associated with other congeni-
– Transperineal cyst aspiration and tal abnormalities of the urinary tract and usu-
sclerotherapy ally occurs as an isolated entity.
– Electrofulgaration • Rarely, a müllerian duct cyst may be associ-
– Open excision (perineal, suprapubic extra- ated with renal agenesis.
vesical, transperitoneal, parasacral, trans- • Rarely, calculi may occur within these cysts.
vesical, transtrigonal, retropubic, posterior • The peak clinical incidence of müllerian duct
and anterior sagittal with rectal retraction, cysts occurs in the age range of 20–40 years,
and transrectal posterior or anterior sagittal as the cyst becomes larger and accumulates
approach) fluid.
– Laparoscopic excision • The clinical presentation is varied, including:
– Robot-Assisted Laparoscopic Excision of – Urinary frequency
Prostatic Utricle Cyst – Urinary urgency
• A suprapubic extravesical and extraperitoneal – Dysuria
approach is a relatively easy and direct – Urinary obstruction
approach. Such an approach was however – Hematuria
reported to have a high rate of incomplete exci- – Pelvic pain
sion. It is feared that total excision may com- • Digital rectal examination may reveal a mid-
promise fertility by traumatically damaging or line cystic mass superior to the prostate gland.
Further Reading 449
Figs. 20.12, 20.13, and 20.14 A clinical intraoperative photograph showing a large utricular cyst being excised. Note
its large size and its relation to the vas deference
• A müllerian duct cyst can be noted on a void- • The müllerian duct cyst and utricle cyst both
ing cystourethrogram or an intravenous uro- occur in the midline; however, the utricle cyst
gram, manifesting as an impression along the is typically smaller, confined to the base of the
posterior wall of the bladder. A müllerian duct prostate, and communicates with the posterior
cyst does not communicate with the urethra urethra.
and so will not be seen on a voiding • Müllerian duct cysts are larger and extend
cystourethrogram. above the base of the prostate.
• Pelvic ultrasound and transrectal ultra-
sound will reveal a fluid-filled cyst project-
ing posterior and superiorly from the Further Reading
prostate, extending posterior to the urinary
1. Bhosle A, Patel S, Desai M. Asymptomatic large pros-
bladder. tatic utricle. Indian J Urol. 2004;20:184–5.
• MRI is a valuable imaging modality for the 2. Buchholz NP. Utricular cyst: a cause of recurrent uri-
evaluation of müllerian duct cysts. nary tract infection. Eur Urol. 1993;24:431–2.
3. Desatuel MG, Stock J, Hanna MK. Mullerian duct 9. Kristic DZ, Smoljanic Z, Micovic Z, et al. Surgical
remnants: surgical management and fertility issues. treatment of the mullerian duct remnants. J Pediatr
J Urol. 1999;162:1008–14. Surg. 2001;36:870–6.
4. Devine Jr CJ, Gonzales-Serva L, Stecker Jr JF, et al. 10. Lane AH, Donahoe PK. New insights into mullerian
Utricular configuration in hypospadias and intersex. inhibiting substance and its mechanism of action.
J Urol. 1980;123:407–11. J Endocrinol. 1998;158:1–6.
5. Donkol RH, Monib S, Mogazy K. Mullerian duct cyst 11. Okur H, Gough DC. Management of mullerian duct
as a cause of acute infantile-onset epididymitis. remnants. Urology. 2003;61:634–7.
Pediatr Radiol. 2006;36:1197–9. 12. Ramachandra M, Bendre PS, Redkar RS, Taide
6. Ikoma F, Shima H, Yabumoto H. Classification of DV. Isolated prostatic utricle. J Indian Assoc Paediatr
enlarged prostatic utricle in patients with hypospa- Surg. 2009;14:228–9.
dias. Br J Urol. 1985;57:334–7. 13. Ritchey ML, Benson Jr RC, Kramer SA, et al.
7. Johal NS, Kraklau D, Deniz K, Mushtaq I. An unusual Management of Mullerian duct remnants in the male
case of a prenatally detected large mullerian duct rem- patient. J Urol. 1988;140:795–9.
nant. Pediatr Surg Int. 2005;21:764–6. 14. Willetts IE, Roberts JP, Mackinnon AE. Laparoscopic
8. Josso N, Cate RL, Picard J-Y, et al. Anti-mullerian excision of a prostatic utricle in a child. Pediatr Surg
hormone: the jost factor. Recent Prog Horm Res. Int. 2003;19:557–8.
1993;48:1–59.
Hypospadias
21
21.1 Introduction • The incidence of hypospadias is higher in

whites than in blacks.
• The term hypospadias is derived from the • Hypospadias is more common in Jewish and
Greek words hypo (below, too little) and Italian people.
Spadone (crack, gutter). • Hypospadias is also more common in the
• Hypospadias is defined as the combination of Caucasian population followed by African-
three anatomical abnormalities of the penis Americans and then the Hispanic
(Figs. 21.1, 21.2, 21.3, and 21.4): Americans.
– Ectopic proximally placed meatus which • The incidence of hypospadias is reported to be
may be located on the ventral side of the increasing in both Europe and North America
penis at any position between the tip of the from an incidence of 20.2 per 10,000 in 1970
glans and the perineum. to a current incidence of 39.7 per 10,000 chil-
– A dorsal winged prepuce and lack of ven- dren born in the U.S.A.
tral prepuce. • The reason for this increase is not exactly
– A ventral penile shaft deviation. known
– The second and third characteristics may • There is a definite familial occurrence of
not necessarily be present. hypospadias. This is estimated to be about
– The megalomeatus is an exception as it is 7 %.
characterized by a complete prepuce and a • In approximately 80–90 % of cases, hypospa-
coronal lying meatus adjacent to a non- dias is of the distal part while the remaining
closed-glans with an open navicular fossa. 10–20 % have proximal hypospadias.
This is also called (MIP) Megameatus with • There is an increased probability for the
Intact Prepuce (MIP) variant of hypospadias. occurrence of hypospadias in the following
• Hypospadias is caused by the arrest of normal situations:
development of the urethra, at various stages – Father with hypospadias
of embryonic development (9–13 weeks of – Low birth weight
pregnancy). – Twin or triplet births
• Hypospadias is among the most common birth – Maternal iron supplements
defects in males. – Smoking mothers
• The exact incidence of hypospadias is not – Fathers with pesticide contact
known but it has been estimated that hypospa- • Chordee is fibrous remnant of the corpus
dias affects approximately 1 of every 200–250 spongiosum distal to the meatus. It extends in
male live newborns. a V shape on both sides, and acts by the lack

452 21 Hypospadias
Figs. 21.1 and 21.2 Clinical photographs showing two patients with hypospadias. The ectopic urethra is located on
the ventral side of the shaft penis. Note the ectopic urethral meatus and also the dorsal winged prepuce
of elasticity producing a ventral deformity more commonly in those with proximal

(Figs. 21.5 and 21.6). hypospadias. This is found in 10 % of
• Chordee (downward bending of the penis) distal hypospadias and 50 % of proximal
is another feature of hypospadias seen hypospadias.
Figs. 21.3 and 21.4 Clinical photographs showing two patients with hypospadias. Note the lack of prepuce ventrally.
Note also the ventral curvature of the penis
Figs. 21.5 and 21.6 Clinical photographs of two patients with hypospadias. Note the shape of chordee and the ventral
curvature of the penis
• Scrotal transposition is seen usually in patients • Characteristically, in the majority of patients

with more proximal hypospadias and it is asso- with hypospadias the foreskin is underdevel-
ciated with bifid scrotum (Penoscrotal transpo- oped and does not wrap completely around the
sition and bifid scrotum) (Figs. 21.7 and 21.8). penis, leaving the underside of the glans penis
Figs. 21.7 and 21.8 Clinical photographs showing scrotal transposition in two patients with hypospadias. Note the
severe hypospadias in the second photograph
454 21 Hypospadias
uncovered by foreskin (Hooded foreskin). The • Hypospadias repair should be performed only
only exception to this is the megameatus. by experienced surgeons and at centers with
• It must be emphasized that not all newborns extensive experience.
with partial foreskin development have hypo- • To emphasize this, Duckett in 1995 coined the
spadias, as some have a normal urinary open- concept of hypospadiologists (surgeons who
ing with a hooded foreskin (This is called subspecialize in hypospadias repair).
“chordee without hypospadias”). • Currently, hypospadias is repaired not only for
• Megameatus with intact prepuce (MIP) vari- functional reasons but also for cosmetic
ant of hypospadias occurs when the foreskin is reasons.
normal and there is a concealed hypospadias. • The postoperative penis should:
The condition is discovered during newborn – Be suitable for normal voiding
circumcision or later in childhood when the – Be suitable for future sexual intercourse
foreskin begins to retract (Figs. 21.9 and – Have an acceptable cosmetic appearance
21.10). • More than 300 different types of repairs have
• The most common associated defect with hypo- been described in the medical literature.
spadias is an undescended testicle, which has • The most common operation to repair hypo-
been reported in approximately 3 % of infants spadias is the tubularized incised plate or
with distal hypospadias and 10 % of those having “TIP” repair. This procedure can be used for
proximal hypospadias (Figs. 21.11 and 21.12). all distal hypospadias repairs.
• In patients with proximal hypospadias, a • There are several techniques to repair proxi-
karyotype and endocrine evaluation should be mal hypospadias as a single stage or two stage
performed to detect disorders of sexual devel- operations.
opment or hormone deficiencies. • There are several factors that contributed
• Using modern surgical techniques, a normal recently to increased success of hypospadias
appearing penis can usually be expected from repair. These include:
hypospadias repair.
Figs. 21.9 and 21.10 Clinical pictures of one patient with megameatus. Note the complete normal looking foreskin.
Note the size of the meatus after retracting the foreskin
21.3 Embryology 455
Figs. 21.11 and 21.12 Clinical photographs of two patients with hypospadias and undescended testes. In the first one,
there are bilateral undescended testes while in the second one there is unilateral undescended testis
– Better understanding of the anatomy of the • Embyologically, the external genitalia are
penis identical in males and females until about
– Improved anesthetic techniques 8 weeks’ gestation.
– Fine instrumentations and sutures – In males, the external genitalia develop a
– Improved dressing materials, and masculine phenotype under the influence
antibiotics of testosterone.
– Testesterone is converted to dihydrotestester-
one under the influence of 5-alpha reductase.
21.2 Effects of Hypospadias – Dihydrotestesterone acts locally to change
the external genitalia into a masculine
• Abnormal urinary stream. The more proxi- phenotype.
mally ectopic the position of the urethral – As the phallus grows, the open urethral
meatus, the more likely the urinary stream groove extends from its base to the level of
is to be deflected downward. Any element the corona.
of chordee can exacerbate this – The urethral folds coalesce in the midline
abnormality. from base to tip, forming a tubularized
• Fertility may be affected as hypospadias may penile urethra and median scrotal raphe.
preclude effective insemination. – This accounts for the posterior and middle
• Painful erection parts of the urethra.
• Psychological stress – The anterior or glanular urethra is thought
to develop in a proximal direction, with an
ectodermal core forming at the tip of the
21.3 Embryology glans penis, which canalizes to join with
the more proximal urethra at the level of
• Hypospadias is a congenital defect that is the corona.
thought to occur during urethral development. – The higher incidence of subcoronal hypo-
• This occurs between 8 and 20 weeks’ spadias supports the vulnerable final step in
gestation. this embryological theory of development.
456 21 Hypospadias
• In 2000, Baskin proposed a modification of may be related to maternal exposure to pro-

this theory in which the urethral folds fuse to gesterone, which is commonly adminis-
form a seam of epithelium, which is then tered in IVF protocols. Progesterone is a
transformed into mesenchyme and subse- substrate for 5-alpha reductase and acts as
quently canalizes by apoptosis or programmed a competitive inhibitor during the process
cell resorption. Similarly, this seam theoreti- of conversion of testosterone to DHT.
cally also develops at the glanular level, and – Hypospadias is also found in the most
the endoderm differentiates to ectoderm with common disorder of sex development, the
subsequent canalization by apoptosis. familial male pseudohermaphroditism.
• The prepuce normally forms as a ridge of skin – Ingestion of substances with estrogenic
from the corona that grows circumferentially, activity, such as insecticides, natural estro-
fusing with the glans. Failure of fusion of the gens, organic products from the manufac-
urethral folds in hypospadias impedes this ture of plastics and pesticides, which are
process, and a dorsal hooded prepuce results. included in food.
• On rare occasions, a glanular cleft with intact – A higher incidence of hypospadias in win-
prepuce may occur. This is termed the mega- ter conceptions has also been proposed.
meatus intact prepuce (MIP) variant. – Increased estradiol concentration in pla-
• Chordee (ventral curvature of the penis) is cental basal syncytiotrophoblasts of boys
often associated with hypospadias, especially with undescended testes.
the more proximal forms of hypospadias. – A genetic predisposition to hypospadias.
– This is thought to result from a growth dis- • There is a genetic predisposition to
parity between the normal dorsal tissue of hypospadias.
the corporal bodies and the attenuated ven- • The inheritance is likely polygenic.
tral urethra and associated tissues. • There is an eight times increased in inci-
– Rarely, the abortive spongiosal tissue and dence of hypospadias among monozy-
fascia distal to the urethral meatus forms a gotic twins.
tethering fibrous band that contributes to • Hypospadias was also shown to be
the chordee. familial.
• The probability to have a second child
with hypospadias is 14 % if the first
21.4 Etiology of Hypospadias child has hypospadias.
• If the father has hypospadias, the prob-
• The etiology of hypospadias is multifactorial ability that one of his sons suffers from
but in the majority (65–75 %) the cause the same pathology is 8 %.
remains unknown. • Hypospadias is present in many syndromes,
• There has been several etiological factors for such as Smith-Lemli-Opitz syndrome or
hypospadias. Robinow syndrome.
• Several etiologies for hypospadias have been • Hypospadias is associated with increasing
suggested, including genetic, endocrine, and parity, increasing maternal age, and low birth
environmental factors. weight.
– Defects in the androgen synthesis or its
action during embryogenesis (A defect in
testosterone biosynthesis). 21.5 Associated Anomalies
– Mutations in the 5-alpha reductase enzyme,
which converts testosterone to the more • A patent processus vaginalis (9 %)
potent dihydrotestosterone (DHT). • Undescended testes and inguinal hernias are
– There is a fivefold increased risk of hypo- the most common anomalies associated with
spadias in males born through IVF. This hypospadias.
Figs. 21.13 and 21.14 Clinical photographs showing severe hypospadias and bilateral undescended testes
• The incidence of undescended testes and

inguinal hernias with hypospadias is about
9 % for each.
• Undescended testis is seen in about 5 % of
mild forms of hypospadias (Figs. 21.13 and
21.14).
• The incidence of undescended testes is more
than 30 % in those with more proximal
hypospadias.
Fig. 21.15 A clinical photograph showing a newborn
• The incidence of inguinal hernias is about with disorder of sexual development resembling hypospa-
20 % in those with more proximal dias clinically
hypospadias.
• The combination of hypospadias and unde-
scended testis should raise the possibility of
an underlying disorder of sexual development
(DSD) (Fig. 21.15).
• DSD were identified in approximately 30 % of
patients with unilateral or bilateral
undescended testes and hypospadias. The
incidence approaches 50 % in those with non-
palpable testes but if the testes are palpable,
the incidence is only 15 %.
• The more proximal hypospadias have a higher
association with DSD.
• A prostatic utricle is another association with
hypospadias. This is more likely so in those
with more proximal hypospadias.
• Sometimes hypospadias is associated with a
low-grade vesicoureteral reflux (Fig. 21.16).
• Upper urinary tract anomalies are rarely asso-
ciated with hypospadias and do not justify Fig. 21.16 A micturating cystourethrogram showing
routine imaging in these patients. mild vesicoureteral reflux in a patient with hypospadias
458 21 Hypospadias
21.6 Classification (50 %), middle (30 %) and posterior (20 %)

of Hypospadias hypospadias.
• These are also sub classified according to the
• There are several classifications for hypospa- location of the meatus:
dias depending on the site of the meatus. – The anterior type:
• One of the oldest classification was that pro- • Glandular
posed by Browne in 1938. • Coronal
– Glandular hypospadias (Figs. 21.17 and • Distal penile
21.18) – The middle type:
– Coronal hypospadias (Figs. 21.19 and 21.20) • Midshaft
– Subcoronal hypospadias (Figs. 21.21 and • Proximal penile
21.22) – The posterior type:
– Distal penile hypospadias (Figs. 21.23 and • Penoscrotal
21.24) • Scrotal
– Midshaft hypospadias (Figs. 21.25 and 21.26) • Perineal
– Proximal penile hypospadias (Figs. 21.27 and • The latest classification was proposed in 2003
21.28) and divides hypospadias into three types.
– Penoscrotal (Figs. 21.29 and 21.30) – Glaular
– Perineal (Figs. 21.31 and 21.32) – Distal
• The most accepted and currently used classifi- – Proximal
cation is the one proposed by Barcat and mod- • The subcoronal hypospadias is the most
ified by Duckett in 1996. He divided the common type.
different types of hypospadias into anterior
Figs. 21.17 and 21.18 Clinical photographs showing glanular hypospadias

21.6 Classification of Hypospadias 459
Figs. 21.19 and 20 Clinical photographs showing coronal hypospadias
Figs. 21.21 and 21.22 A clinical photograph showing subcoronal hypospadias

460 21 Hypospadias
Figs. 21.23 and 21.24 Clinical photographs showing distal penile hypospadias
Figs. 21.25 and 21.26 Clinical photographs showing midshaft hypospadias

21.6 Classification of Hypospadias 461
Figs. 21.27 and 21.28 Clinical photographs showing proximal hypospadias
Figs. 21.29 and 21.30 Clinical photographs showing penoscrotal hypospadias

462 21 Hypospadias
Figs. 21.31 and 21.32 Clinical photographs showing perineal hypospadias
21.7 Clinical Features tip of the glans penis (Figs. 21.33, 21.34, and
of Hypospadias 21.35).
• The urethral opening may be located as far
• The urethral opening is ectopically located on down as in the scrotum or perineum.
the ventral aspect of the penis proximal to the • There is usually an associated glanular groove.
Figs. 21.33 and 21.34 Clinical photographs showing hypopsadias. Note the abnormal ectopic meatus on the ventral
surface of the peis. Note also the glanular groove
21.7 Clinical Features of Hypospadias 463
The depth of this groove is variable.

• A dorsal hood of foreskin is present and the
prepuce is incomplete ventrally (“hooded”
foreskin).
• Rarely, the foreskin may be complete, and the
hypospadias is revealed at the time of circum-
cision. This is called the mega meatus intact
prepuce (MIP) variant of hypospadias
(Figs. 21.36 and 21.37).
• The penis may have associated ventral short-
ening and curvature (chordee). This may be
apparent during erection only and it is more
commonly seen in patients with more proxi-
Fig. 21.35 A clinical photograph showing hypospadias.
mal hypospadias (Figs. 21.38 and 21.39). Note the deep glandular groove and the ectopic meatus on
the ventral aspect of the penis
Figs. 21.36 and 21.37 Clinical photographs showing megameatus. Note the normal looking prepuce and also note the
wide meatus
Figs. 21.38 and 21.39 Clinical photographs showing severe chordee associated with hypospadias
464 21 Hypospadias
Figs. 21.40 and 21.41 Clinical photographs showing abnormal prepuce that is deficient ventrally but a normal look-
ing meatus both in size and position
• Proximal hypospadias is commonly associ- effect and to decrease this effect, repair of
ated with a bifid scrotum and penoscrotal hypospadias is currently done at an earlier age
transposition. group (6–18 months). This is known to have
• There may be an associated undescended tes- an improved emotional and psychological
tes which can be unilateral or bilateral. result.
• On rare occsions, the foreskin may appear • Repair of mild degrees of hypospadias is
abnormal resembling hypospadias but the mainly for cosmetic reasons as they have little
meatus appears normal in position and site effect on function except for the direction of
(Figs. 21.40 and 21.41). the urinary stream.
• The aim from the surgical repair is to have a
penis that has an acceptable appearance,
21.8 Treatment enable the patient to void normally and suit-
able for sexual intercourse in the future
• It is important to avoid circumscion in these • Hormonal therapy (Figs. 21.45, 21.46, and
children as the preputial skin is often used for 21.47):
grafting during hypospadias repair. The dartos – Hormonal therapy has been used as an
flap of the preputial skin is dissected and used adjuvant for infants with small phallic size.
to protect the repair either as a single or dou- – The aim is to increase the length and width
ble layers. This was shown to decrease the rate of the penis.
of postoperative fistula formation. The prepu- – Testosterone injections or creams can be
tial skin is sometimes used to cover the used.
deficient skin ventrally as Byer’s flaps • The recommended testosterone injection
(Figs. 21.42, 21.43, and 21.44). dose (long acting testosterone) is about 2 mg/
• Currently, most cases of hypospadias are kg/dose. This is given once every 3 weeks
repaired in the first 18 months of life and in a and can be repeated to a maximum of three
single stage (usually between 6 and 18 months doses.
of age. • Human chorionic gonadotropin (HCG) injec-
• Hypospadias and hypospadias repair is known tions, have been used also to promote penile
to be associated with significant psychological growth.
21.8 Treatment 465
Figs. 21.42, 21.43, and 21.44 Clinical intraoperative photographs showing the use of Dartos flaps as a single or
double to protect the hypospadias repair
• The treatment of hypospadias is surgical • The chordee is repaired during the first stage,
repair, not only for functional reasons but also and the urethroplasty and glansplasty are
for cosmetic reasons. repaired after the first stage has completely
• Hypospadias repair is generally performed as healed.
a single-stage procedure. • Hypospadias repair is done under general
• A staged hypospadias repair is preferable in anesthesia, most often supplemented by a
those with excessive chordee, and a small nerve block to the penis or a caudal block in
phallic size. order to reduce the general anesthesia needed,
466 21 Hypospadias
Figs. 21.45, 21.46, and 21.47 Clinical photographs width of the penis. Note also the appearance of pubic hair
show in hypospadias before and after long acting testest- as a side effect of long acting testesterone
erone injection. Note the increase in both the length and
and to minimize discomfort and pain after • There are those who will not repair minor
surgery. cases of hypospadias, in which the meatus is
• The goals of surgical treatment of hypospa- located near the tip of the glans.
dias are as follows (Figs. 21.48 and 21.49): • Hypospadias and hypospadias repair is known
– To create a straight penis by repairing any cur- to be associated with significant psychological
vature (orthoplasty) effect and to decrease this effect, repair of
– To create a urethra with its meatus at the tip of hypospadias is currently done at an earlier age
the penis (urethroplasty) group (6–18 months).
– To re-form the glans into a more natural coni- • This is known to have an improved emotional
cal configuration (glansplasty) and psychological result.
– To achieve cosmetically acceptable penile • There are several surgical techniques to repair
skin coverage hypospadias depending on the site of urethral
– To create a normal-appearing scrotum
21.8 Treatment 467
Figs. 21.48 and 21.49 Clinical photographs showing posthypospadias repair
meatus and the presence or absence of – Very mild degree of glanular hypospadias
chordee. can be repaired with meatoplasty.
• Any degree of chordee should be corrected – There are those who advocate leaving a
prior to urethroplasty. very mild degree of hypospadias without
• This may necessitates transection of the ure- repair.
thral plate in severe cases, precluding its use • Middle hypospadias:
for urethroplasty (Figs. 21.50 and 21.51). – There are several techniques to repair this
• Residual chordee is a known case of failure of type of hypospadias.
urethroplasty. Add to this the bad cosmetic – The TIP or Snodgrass urethroplasty (The
appearance. tubularized incised plate urethroplasty)
• Glanular hypospadias: (Figs. 21.52, 21.53, 21.54, 21.55, 21.56,
– This is commonly repaired using: 21.57, 21.58, and 21.59):
• The MAGPI (Meatal Advancement • This is the commonest procedure used to
Glanduloplasty Incorporated) repair anterior hypospadias (coronal, subcoro-
procedure. nal, distal penile and midshaft hypospadias).
• The DYG (The Double Y Glanuloplasty) • A midline incision into the urethral plate
procedure. widen it sufficiently for urethroplasty without
• Others continue to use perimeatal-based stricture formation.
flaps for urethroplasty (“flip-flap • This is suitable for cases without chordee or
repair”). mild degrees of chordee.
468 21 Hypospadias
Figs. 21.50 and 21.51 Clinical photographs showing proxial hypospadias with severe chordee. Note the penile length
after release of chordee and how straight it became
– The Mathieu Technique: • It is suitable for cases with chordee as it

• This was modified and called The allows for extensive excision of ventral
Slit-like adjusted Mathieu (SLAM) chordee and the urethral plate without
Technique. damaging the flap.
• The meatal-based flap technique of – Transverse Preputial Island Flap
Mathieu was the most popular tech- – Onlay Island Flap: The Onlay Island Flap
nique for distal hypospadias repair. is ideal for patients with proximal hypospa-
• This technique is not commonly used dias without deep Chordee
now. • Posterior hypospadias (Figs. 21.60, 21.61,
• It is also not suitable for cases with 21.62, 21.63, 21.64, and 21.65):
chordee. – There is less consensus regarding proximal
• The major drawback of the original hypospadias repair.
Mathieu technique is the final appear- – Most of these cases are repaired using a two
ance of the meatus (a smiling meatus Stage repair.
that is not very terminal). – These as well as a small group of patients with
– The LABO technique (Lateral Based Onlay severe proximal hypospadias, chordee, and a
Flap): small phallus.
• The principle of this technique is to use – Patients with recurrent hypospadias and
the lateral penile skin as well as part of fibrous unhealthy skin may benefit from a
the prepuce to reconstruct the new two-stage procedure.
urethra. – In the first stage, the chordee is excised com-
– Lateral Based Flap: pletely and this confirmed by the use of the
• The lateral based flap may be used in all artificial erection test.
types of proximal hypospadias. • The second stage of the procedure is carried
• This flap combines the advantages of out 6–12 months later.
meatal-based flap, and preputial pedicle • The tubularized incised plate (TIP) repair has
flap techniques into one procedure with- become the most commonly used repair for
out the need for an intervening both distal and midshaft hypospadias. This
anastomosis. procedure can be used for all distal hypospa-
21.8 Treatment 469
Figs. 21.52, 21.53, 21.54, 21.55, 21.56, 21.57, 21.58, and 21.59 Clinical photographs showing the steps of TIP
procedure. The repair was reinforced with a double layer of dartos flaps
470 21 Hypospadias
Figs. 21.52, 21.53, 21.54, 21.55, 21.56, 21.57, 21.58, and 21.59 (continued)
21.8 Treatment 471
Figs. 21.60, 21.61, and 21.62 Clinical photograph showing the second stage repair of proximal hypospadias after
release of chordee. The ventral skin defect was covered with a Byer’s flaps
Figs. 21.63, 21.64, and 21.65 Clinical photographs showing proximal hypospadias without chordee that was repaired
using TIP technique
472 21 Hypospadias
dias repairs, with postoperative complications • There those who do not use routine urinary
less than 10 % of cases. TIP repair can also be diversion while others prefer routine urinary
used to repair more proximal hypospadias diversion for all cases of hypospadias.
when the penis is straight or has mild down- • Postoperative urinary diversion is performed
ward curvature. to prevent urination against the newly created
• Various sutures have been used to repair of urethra.
hypospadias. • This is supposed to support wound healing.
• The buccal mucosa has been used for urethral • The use of urinary diversion restrict the activ-
grafting mainly for repeat repairs after unsuc- ity of the child and may necessitates prolonged
cessful surgery for hypospadias. This is spe- hospitalization especially those with a supra-
cially so for patients who already had pubic urinary diversion.
circumscion. • There are three different types of urinary
• There are several methods used to decrease diversion (Figs. 21.66 and 21.67):
the risk of fistula. One method is to increase – Suprapubic urinary diversion (cistofix)
the layers of tissue between the urethra and – Transurethral urinary diversion with a balloon
overlying skin using dartos flaps either single catheter (Foley’s catheter)
or double flaps. – Transurethral urinary diversion with a “drip-
ping stent”, which drains the bladder on a
diaper.
21.9 Urinary Diversion • The duration of catheter drainage is variable
ranging from 5 to 10 days depending on the
• The use of postoperative urinary diversion is extent of repair.
still controversial. • Catheter drainage is also valuable in eliminat-
• The importance of urinary diversion for pre- ing the possibility of acute urinary retention as
venting postoperative complications is not this makes postoperative catheterization diffi-
clear. cult and potentially harmful.
Figs. 21.66 and 21.67 A clinical photograph showing dressing and urinary diversion with a Foley’s catheter following
repair of hypospadias
21.10 Postoperative Complications 473
21.10 Postoperative Complications – Postoperative bleeding and hematoma

formation
• Repair of hypospadias is known to be associ- – Glans dehiscence
ated with complications. – Wound dehiscence
• Repair of the more proximal hypospadias are – Flap or graft necrosis
known to be associated with a greater inci- – Urinary tract infections
dence of complications. – Urinary tract obstruction
• Immediate postoperative complications: – Catheter blockage
– Local edema – Infection is a rare complication of hypo-
– Bruising spadias repair
Figs. 21.68, 21.69, 21.70, and 21.71 Clinical photographs showing urethral fistulae following repair of
hypospadias
474 21 Hypospadias
• Long-term complications: – Meatal stenosis (7–15 %):

– Urethrocutaneous fistula (Figs. 21.68, • Another common complication of hypo-
21.69, 21.70, and 21.71): spadias is narrowing of the urethral
• A fistula is an unwanted opening through the meatus.
skin along the course of the urethra, and can • This may be cured with urethral dilata-
result in urinary leakage or an abnormal tion or meatoplasty.
stream. – Urethral strictures (Fig. 21.72):
• This is one of the common complications of • These are long-term complication of hypospa-
hypospadias repair and a major concern. dias repair.
• The incidence of fistula is variable and • A stricture is a narrowing of the urethra severe
depends on the type of hypospadias and the enough to obstruct flow.
repair used. • Dilatation is not effective in treating these
• Generally, the rate of fistula formation is less strictures.
than 10 % for most single-stage repairs • These are generally repaired operatively and
(5–10 %). may require incision, excision with reanasto-
• This however rises with the severity of hypo- mosis, or patching with a graft or pedicle skin
spadias, approaching 40 % with complex more flap.
proximal hypospadias. – Urethral diverticula (Figs. 21.73, 21.74,
• There are reports of spontaneous closure of and 21.75):
fistula but this extremely rare. • A urethral diverticulum is an “outpocketing”
• Fistulas are repaired by using a multilayered of the lining of the urethra which interferes
closure with local skin flaps 6 months after the with urinary flow and may result in post-
initial repair. urination leakage.
• After repair, fistulas recur in approximately • This lead to ballooning of the urethra while
10 % of patients. voiding.
• Urethral diverticulum is also a cause of post
void drippling of urine.
• It also causes recurrent urinary tract
infection.
• There is usually an associated distal stricture
which causes outflow obstruction.
• Diverticula can also form in the absence of
distal obstruction and are generally associated
with graft- or flap-type hypospadias repairs,
which lack the subcutaneous and muscular
support of native urethral tissue.
• The treatment is surgical excision of the diver-
ticulum, the redundant urethral tissue and
tapering of the urethra over a Foley’s
catheter.
– Hairy urethra:
• Hair-bearing skin should be avoided in
hypospadias repair.
• The use of hair- bearing skin will lead to
hairy urethra which is known to be
problematic and can result in repeated
Fig. 21.72 A micurating cystourethrogram showing ure- urinary tract infection or stone
thral stricture following repair of hypospadias formation.
21.10 Postoperative Complications 475
Figs. 21.73, 21.74, and 21.75 Clinical and intraoperative photographs showing urethral diverticulum following repair
of hypospadias. Note the diverticulum full of urine. It also causes postvoid driplling of urine
• The treatment is cystoscopic depilation

using a laser or cautery device.
• In severe cases, the hair-bearing skin
can be excised and a repeat hypospadias
is done.
– Rarely, hypospadias is associated with
mild degrees of erectile dysfunction. This
is more seen in those with more proximal
hypospadias repairs.
– Scarring is usually seen in patients follow-
ing hypospadias repair. This is seen more
in patient who underwent repeated attempts
of hypospadias repair.
– Penile curvature is sometimes seen follow-
ing hypospadias repair. Fig. 21.76 A clinical photograph showing penile devia-
tion following repair of hypospadias
– Deviated penis (Fig. 21.76):
476 21 Hypospadias
• This can be seen following urethroplasty 5. Duckett JW. Successful hypospadias repair. Contemp
Urol. 1992;4:42–55.
where the penis deviates to one side.
6. Duckett JW. Hypospadias. In: Walsh PC, Retik AB,
• The degree of deviation is variable. Vaughan ED, et al., editors. Campbell’s urology. 7th
• Mild degrees of deviation can be treated con- ed. Philadelphia: WB Saunders Co; 1998.
servatively while those with severe degrees p. 2093–119.
7. Duckett JW, Coplen D, Ewalt D. Buccal mucosal ure-
need correction.
thral replacement. J Urol. 1995;153(5):1660–3.
• This can be achieved with plication 8. Gearhart JP, Jeffs RD. The use of parenteral testoster-
technique. one therapy in genital reconstructive surgery. J Urol.
1987;138(4 Pt 2):1077–8.
9. Hadidi AT, Azmy AF. “Hypospadias surgery: An
Illustrated Guide”; library of congress cataloging-in-
publication. Berlin: Springer-Verlag; 2004.
Further Reading 10. Snodgrass WT. The “learning curve” in hypospadias
surgery. BJU Int. 2007;100(1):278–81.
1. Baskin LS. Hypospadias and urethral development. 11. Snodgrass W. Surgical atlas: Snodgrass technique for
J Urol. 2000;163(3):951–6. hypospadias repair. Dallas: Department of Paediatric
2. Chung JW, Choi SH, Kim BS, Chung SK. Risk fac- Urology, Children’s Medical Center of Dallas and
tors for the development of urethrocutaneous fistula University of Texas, South-western Medical Center at
after hypospadias repair: a retrospective study. Korean Dallas; 2009.
J Urol. 2012;53(10):711–5. 12. Snodrass WT. Tubularized incised plate hypospadias
3. Cook A, Khoury AE, Neville C, et al. A multicenter repair: indications, technique, and complications.
evaluation of technical preferences for primary hypo- Urology. 1999;54(1):6–11.
spadias repair. J Urol. 2005;174(6):2354–7. 13. Springer A, Reck CA, Huber C, Horcher E. Online
4. Dodson JL, Baird AD, Baker LA, Docimo SG, hypospadias support group data analysis. J Pediatr
Mathews RI. Outcomes of delayed hypospadias Surg. 2011;46(3):520–4.
repair: implications for decision making. J Urol. 14. Wang MH, Baskin LS. Endocrine disruptors, genital
2007;178(1):278–81. development, and hypospadias. J Androl.
2008;29(5):499–505.
Male Circumcision
22
22.1 Introduction • Circumcision is relatively rare in Europe,

Latin America, parts of Southern Africa and
• Male circumcision is derived from Latin cir- most of Asia.
cumcidere, meaning “to cut around”. • Circumcision is most prevalent in:
• It is defined as the surgical removal of the – The Muslim world
foreskin (prepuce) from the human penis – Israel
(Fig. 22.1). – South Korea
• The origin of male circumcision is not known – The United States of America
with certainty. – Parts of Southeast Asia and Africa
• The oldest documentary evidence for circum- • Circumcision is relatively rare in Europe,
cision comes from ancient Egypt. Latin America, parts of Southern Africa and
• It is part of religious law in Judaism and is Oceania and most of Asia.
an established practice in Islam, Coptic • Non-religious circumcision in Asia, outside of
Christianity and the Ethiopian Orthodox the Republic of Korea and the Philippines, is
Church. fairly rare.
• The practice and frequency of circumcision is
different worldwide.
• Circumcision is one of the world’s most
widely performed procedures.
• The frequency of circumcision varies world-
wide depending on geographic location,
religious affiliation, and socioeconomic
classification.
• Approximately one-third of males worldwide
are circumcised, most often for religious or
cultural reasons.
• The procedure is most prevalent in the Muslim
world and Israel (where it is near-universal as
a religious obligation), the United States and
parts of Southeast Asia and Africa.
• Almost 70 % of circumcised children are Fig. 22.1 A clinical photograph showing an uncircum-
Muslim. cised infant

478 22 Male Circumcision
• The prevalence of circumcision is generally

low (<20 %) across Europe.
• The estimated prevalence of circumcision for
individual countries is as follows:
– Taiwan 9 %
– Australia 58.7 %
– The United States 75 %
– Canada 30 %
– In Africa, the prevalence varies from less
than 20 % in some southern African
countries to near universal in North and
West Africa.
• In the United States of America, neonatal cir-
cumcision rates are different among racial and
ethnic groups:
Fig. 22.2 A clinical photograph of a child following for-
– 81 % in whites mal surgical circumcision
– 65 % in African-Americans
– 54 % in Hispanics
• Circumcision is performed by general practi-
tioners, family physicians, general surgeons,
urologist, pediatric surgeons, pediatric urolo-
gist, plastic surgeons, pediatricians and
obstetricians.
• In the United States of America, approxi-
mately 70 % of obstetricians, 60 % of family
practitioners, and 35 % of pediatricians prac-
tice newborn circumcision.
• In some countries, circumcision is also per-
formed by nurses, midwives and non-
professional not well trained persons.
Fig. 22.3 A clinical photograph showing an infant fol-
• The procedure is most often performed on lowing plastibel circumcision
neonates and children for religious and cul-
tural reasons.
• In other cases, circumcision is performed to • It was found that the benefits of circumcision
treat or prevent complications. These include outweigh the risks.
(Figs. 22.2 and 22.3): • This was supported by the fact that “Over their
– Pathological phimosis and paraphimosis lifetime, half of uncircumcised males will
– Refractory balanoposthitis require treatment for a medical condition
– Chronic urinary tract infections (UTIs) associated with retention of the foreskin.”
– Part of the corrective treatment of • Others consider elective neonatal and child
hypospadias, epispadias and chordee and circumcision as having no benefit and signifi-
ambiguous genitalia. cant risks to having a modest health benefit
• Circumcision is associated with reduced rates that outweighs small risks.
of HPV related cancer and risk of both UTIs • Routine circumcision is not recommended by
and penile cancer. many medical organizations.
• It must be emphasized that circumcision does • The World Health Organization (WHO) rec-
not appear to have a negative impact on sexual ommends circumcision for parts of Africa with
function. high rates of HIV as part of a comprehensive
22.2 Anatomy and Pathophysiology 479
HIV program. Evidence supports that male cir- 22.2 Anatomy

cumcision reduces the risk of HIV infection and Pathophysiology
among heterosexual men.
• There are several techniques used in neonatal • The prepuce (foreskin) is formed as a result of
circumcision. folding of the penile skin on itself at the level
• The three most common devices used to date of the corona.
are: • This folded foreskin covers the glans penis.
– The Gomco clamp (67 %) • The corona is the grove that separate the shaft
– The Plastibel device (19 %) of the penis from the glans.
– The Mogen clamp (10 %). • The glans is covered with smooth hairless
• Both the Gomco clamp and the Mogen clamp skin.
are excellent instruments for infants but • The subcutaneous connective tissue of the penis
should not be used in toddlers who weigh and scrotum has a distinct layer with abundant
more than 5 kg because of an increased risk of smooth muscle called the dartos fascia.
bleeding. • This layer continues into the perineum and
• Cosmetic results are excellent with any of fuses with the superficial perineal (Colle’s)
these devices if they are used correctly. fascia.
• The bone cutter is rarely used now. • In the penis, the dartos fascia is loosely
• Plastibel circumcision can be used safely in attached to the skin and deep penile (Buck’s)
children up to 10 kg under local anesthesia. fascia and contains the superficial arteries,
• Plastibel circumcision induces tissue necrosis veins, and nerves of the penis.
by means of suture compression of the fore- • The prepuce that covers the glans penis, is
skin over a plastic ring that protects the glans. lined up by two layers, an external keratinized
The skin sloughs off in 5–7 days, and the ring layer and an internal mucosal layer.
separates spontaneously. • This creates a pouch between these two
• Plastibel circumcision is not without compli- linings.
cations which include: • The pouch thus created can collect desqua-
– Bleeding mated epithelial cells forming the so-called
– Failure of the plastibel to fall and needs to keratin pearls in infants and toddlers.
be removed manually or cut • In adolescence, cellular debris and local secre-
– Migration of the plastibel backward to the tions collect in the form of smegma if the
shaft and the plastibel needs to be cut penis is not cleaned regularly.
– The use of improper size of plastibel can • These secretions of the prepuce provides pro-
lead to incomplete circumcision. tection to the glans from dryness and
• Circumcision is not without complications keratinization.
and have been reported to have a median com- • The nerve supply of the prepuce is from the
plication rate of 1.5 % for newborns and 6 % dorsal nerve of the penis and branches of the
for older children. perineal nerve. The autonomic nerve supply is
• These complication rates are higher when the primarily from the pelvic plexus.
procedure is performed by an inexperienced • Groups that oppose neonatal circumcision
doctor. These complications include: argue that:
– Bleeding – The foreskin has specialized nerve endings
– Infection that enhance sexual pleasure.
– Removal of either too much or too little – The foreskin has important functions,
foreskin including natural protection of the glans
– A more serious complication is cutting part penis.
or whole glans penis – Permanent externalization of the glans
– Iatrogenic hypospadias (urethral fistula) penis results in desensitization due to
keratinization of the glans that buries nerve – As a mark of cultural identity

endings deep into this structure. – As a ceremonial offering to the gods
• Smegma is formed by desquamated epithelial • Ritual circumcisions in Middle Eastern cul-
cells trapped between the glans penis and tures have been practiced for at least
foreskin through a natural process that aids in 3,000 years.
the normal separation of the glans from the • Late in the nineteenth century, this ancient
foreskin. It appear as a white, cheese like sub- ritual evolved into routine medical practice
stance (smegma) and it is considered a normal influenced by reports that associated it with
finding that is not indicative of infection. miraculous cures for hernias, paralysis, epi-
lepsy, insanity, masturbation, headache, stra-
bismus, rectal prolapse, hydrocephalus,
22.3 History of Circumcision clubfoot, asthma, enuresis, and gout.
• Circumcision is commonly practiced in the
• Circumcision is the world’s oldest surgical Jewish and Islamic faiths.
procedure. • Circumcision is very important to most
• The origins of circumcision is not well known. branches of Judaism, with over 90 % of
• Some have suggested that this procedure orig- adherents having the procedure performed as
inated in Egypt some 15,000 years ago and a religious obligation.
that its practice later spread throughout the • In addition to proposing that circumcision was
world during prehistoric human migrations. taken up by the Israelites purely as a religious
• This was supported by the findings of Egyptian mandate, scholars have suggested that Judaism’s
mummies and wall carvings discovered in the patriarchs and their followers adopted circumci-
nineteenth century documenting some of the sion to make penile hygiene easier in hot, sandy
earliest records of circumcision dating this climates; as a rite of passage into adulthood; or
procedure to at least 6,000 years BC. as a form of blood sacrifice
• However, other authors believe that circumci- • Jewish circumcision is part of the brit milah
sion developed independently in different ritual, to be performed by a specialist ritual
cultures. circumciser (a mohel) on the eighth day of a
• Columbus on his arrival to the New World newborn son’s life (with certain exceptions for
found that many of the natives were already poor health).
circumcised. • Jewish law requires that the circumcision
• In the lands south and east of the Mediterranean, leave the glans bare when the penis is flaccid.
starting with Sudan and Ethiopia, the proce- • Circumcision (called khitan) is practiced
dure was practiced by the ancient Egyptians nearly universally by Muslim males.
and the Semites, and then by the Jews and • Although it is not explicitly mentioned in the
Muslims, with whom the practice travelled to Quran, circumcision is considered essential to
and was adopted by the Bantu Africans. Islam, and it is nearly universally performed
• In Oceania, circumcision is practiced by the among Muslims.
Australian Aborigines and Polynesians. • Circumcision is a tradition established by
• Evidence suggests that circumcision was Islam’s prophet Muhammad directly, and so
practiced in the Arabian Peninsula by the its practice is considered a Sunnah (prophet’s
fourth millennium BCE, when the Sumerians tradition) and is very important in Islam.
and the Semites moved into the area that is • The practice of circumcision spread across the
modern-day Iraq. Middle East, North Africa and Southern
• Many cultures have historically used Europe with Islam.
circumcision: • There is no agreement across the many Islamic
– For hygienic reasons communities about the age at which circumci-
– As a rite of passage to manhood sion should be performed.
22.3 History of Circumcision 481
• It may be done from soon after birth up to many of the previously accepted medical indi-
about age 15; most often it is performed at cations have come under considerable
around 6–7 years of age. scrutiny.
• The timing can correspond with the boy’s • The first medical doctor to advocate for the
completion of his recitation of the whole adoption of circumcision, was the eminent
Quran, with a coming-of-age event such as English physician, Jonathan Hutchinson. In
taking on the responsibility of daily prayer. 1855, he published a study in which he com-
• Circumcision is considered a major event and pared the rate of contraction of venereal dis-
usually celebrated with an associated family ease amongst the gentile and Jewish population
or community. of London. His study appeared to demonstrate
• Christianity does not require circumcision; that circumcised men were significantly less
Christianity does not forbid it either. vulnerable to such disease.
• The Catholic Church currently maintains a • Circumcision was also employed as a means of
neutral position on the practice of non- discouraging masturbation. Circumcision was
religious circumcision, although in 1442 it also recommended to prevent masturbation.
banned the practice of religious circumcision. • In America, one of the first modern physicians
• Coptic Christians practice circumcision as a to advocate circumcision was Lewis Sayre, a
rite of passage. founder of the American Medical Association.
• The Ethiopian Orthodox Church calls for cir- In 1870, Sayre began using circumcision to
cumcision, with near-universal prevalence prevent or as a cure for several array of medi-
among Orthodox men in Ethiopia. cal problems and social ills. As a result of his
• In South Africa, some Christian churches dis- publications and promotion, in both America
approve of the practice, while others require it and Great Britain, infant circumcision was
of their members. near universally recommended.
• In the Philippines, circumcision known as • In 1949, Douglas Gairdner showed that the
“tuli” is sometimes viewed as a rite of passage. risks of circumcision outweighed the known
About 93 % of Filipino men are circumcised. benefits.
• Certain African cultural groups, such as the • In the 1970s, national medical associations in
Yoruba and Igbo of Nigeria, customarily cir- Australia and Canada issued recommenda-
cumcise their infant sons. tions against routine infant circumcision.
• The procedure is also practiced by some cul- • The United States made similar statements in
tural groups or individual family lines in the the 1970s, but stopped short of recommending
Sudan, Zaire, Uganda and in southern Africa. against it—simply stating that it has no medi-
• For some of these groups, circumcision cal benefit.
appears to be purely cultural, done with no • Subsequently, they have amended their policy
particular religious significance or intention to statements several times. The current recom-
distinguish members of a group. mendation being that the benefits outweigh
• For others, circumcision might be done for the risks, but they do not recommend it
purification, or it may be interpreted as a mark routinely.
of subjugation. • Because neonatal circumcision poses both
• Among these groups, even when circumcision potential benefits and risks and because the
is done for reasons of tradition, it is often done procedure is not necessary for a child’s well-
in hospitals. being, the American Academy of Pediatrics
• It is not clear how many deaths and injuries (AAP) Task Force on Circumcision in its lat-
result from traditional circumcisions which est policy statement in 1999 affirms that
occur outside of hospitals. “existing scientific evidence demonstrates
• Routine neonatal circumcision has become a potential benefits of newborn male circumci-
controversial issue in the past two decades as sion; however, these data are not sufficient to
recommend routine neonatal circumcision.” 22.4 Pain Management

As a consequence, parents should be appropri-
ately counseled so that they can make an • It is well known that circumcision causes pain,
informed choice and decide whether a circum- and for neonates this pain may interfere with
cision is in the best interest of their child. mother-infant interaction or cause other
• Worldwide, most legal jurisdictions do not behavioral changes.
have specific laws concerning the circumci- • To avoid this, pre and post circumcision anal-
sion of males. gesia is advocated.
• Infant circumcision is considered legal under • There are several methods to achieve this.
the existing laws in countries such as Australia, – Paracetamol orally or suppository
Canada, New Zealand, the United Kingdom, – Topical analgesic creams (EMLA cream
and the United States. which is a mixture of prilocaine and
• A few countries have passed legislation on the lidocaine)
procedure: Germany allows non-therapeutic – Localized or regional nerve blocks (ring
circumcision under certain conditions, while block and dorsal penile nerve block)
routine neonatal circumcision is illegal in – The ring block and dorsal penile nerve
Finland, non-religious routine circumcision is block (DPNB) are the most effective at
illegal in South Africa and Sweden. reducing pain.
• In the 9th edition of the Encyclopedia – The ring block may be more effective than
Britannica published in 1876, discusses the the DPNB.
practice of circumcision as a religious rite – The ring block and dorsal penile nerve
among Jews, Muslims, the ancient Egyptians block are more effective than EMLA
and tribal peoples in various parts of the cream.
world. • Non-pharmacological methods to reduce cir-
• In 1910 the Encyclopedia Britannica changed cumcision pain include:
the statement regarding circumcision: “This – The use of a comfortable, padded chair
surgical operation, which is commonly pre- – The use of a sucrose or non-sucrose
scribed for purely medical reasons, is also an pacifier
initiation or religious ceremony among Jews • The American Academy of Pediatrics (AAP)
and Muslims”. states that such methods are insufficient alone
• An association between circumcision and and should be used to supplement more effec-
reduced heterosexual HIV infection rates was tive techniques.
suggested in 1986. To establish this, trials took • A quicker procedure to do circumcision
place in South Africa, Kenya and Uganda and reduces duration of pain.
showed the circumcised group had a lower • The use of the Mogen clamp was found to
rate of HIV contraction than the control group. result in a shorter procedure time and less
• Subsequently, the World Health Organization pain-induced stress than the use of the Gomco
promoted circumcision in high-risk popula- clamp or the Plastibel.
tions as part of an overall program to reduce • Formal surgical circumcision in older children
the spread of HIV. is done under general anesthesia. This can be
• The Male Circumcision Clearinghouse web- supplemented with a caudal block to reduce
site was formed in 2009 by WHO, UNAIDS, postoperative pain.
FHI and AVAC to provide current evidence-
based guidance, information and resources to
support the delivery of safe male circumcision 22.5 Indications for Circumcision
services in countries that choose to scale up
the procedure as one component of compre- • Circumcision is commonly performed for cul-
hensive HIV prevention services. tural, religious, or hygienic reasons.
22.5 Indications for Circumcision 483
• Medical indications for circumcision include: – Paraphimosis is a true urologic emergency

– Phimosis and should be treated as soon as possible.
– Paraphimosis – If not treated promptly, it can result in
– Balanitis and posthitis venous engorgement and edema of the
– Recurrent urinary tract infection glans and foreskin which, over time, pro-
– Children who require clean, intermittent gresses to arterial occlusion and the risk of
catheterization ischemic loss of portions or the entire glans
– Part of the repair of hypospadias, epispa- penis.
dias and ambiguous genitalia – Paraphimosis is treated by manual reduc-
• Phimosis: tion of the prepuce over the glans.
– Phimosis is a condition in which the distal – If manual reduction fails, a dorsal incision
prepuce cannot be retracted over the glans at the level of the constricting band releases
penis. the foreskin.
– Severe phimosis can be demonstrated by – Circumcision should later be performed
bulging of the foreskin during micturition. electively.
– Phimosis causes chronic skin irritations, • Balanitis or posthitis:
yeast infections, balanitis, posthitis, and – Posthitis is an infection of the prepuce,
the forceful retraction of the foreskin may whereas balanitis is an infection of the
result in paraphimosis. glans penis.
– Phimosis may cause pain and difficulty – An inflammation of the glans penis and
during micturition and may cause pain dur- foreskin is called balanoposthitis
ing sexual activity. – Balanitis and posthitis may be the result of
– Acquired or pathological phimosis occurs poor hygiene.
as a result of: – Most cases occur in uncircumcised males,
• Poor hygiene affecting 4–11 % of uncircumcised males.
• Chronic or repeated episodes of – The moist, warm space underneath the
balanoposthitis foreskin is thought to facilitate the growth
• Repetitive forceful retraction of the of pathogens, particularly when hygiene is
foreskin poor.
• Scaring from the skin disease balanitis – The infection is usually caused by mixed
xerotica obliterans (BXO) flora.
• Circumcision complication – Yeasts, especially Candida albicans, are
– Circumcision is the treatment for patho- the most common penile infection
logical phimosis. – Trichomonal balanitis and candidal infec-
• Paraphimosis: tions may be seen in sexually active
– Paraphimosis is the inability to reduce a teenagers.
retracted foreskin over the glans penis to its – Posthitis is characterized by erythema,
naturally occurring position. swelling, warmth, and tenderness of the
– Paraphimosis can result when parents or foreskin.
physicians forcibly retract the foreskin to – Balanitis is characterized by erythema,
clean the penis or attempt catheterization swelling, warmth, and tenderness of the
and do not return the foreskin to its original glans penis.
position. – A foul-smelling, thin, seropurulent exudate
– Edema, tenderness, and erythema of the may be seen.
glans are seen, along with edema of the dis- – Both of these infections are treated with
tal foreskin and flaccidity of the penile oral and topical antibiotics and warm baths.
shaft proximal to the areas of – Circumcision is a treatment option for
paraphimosis. refractory or recurrent balanoposthitis.
• Management of urinary tract infections: – Circumcision is recommended as part of a

– A urinary tract infections affects parts of comprehensive program for prevention of
the urinary system including the urethra, HIV transmission in areas with high
bladder, and kidneys. endemic rates of HIV.
– There is about a 1 % risk of UTIs in boys – Evidence among heterosexual men in sub-
under 2 years of age, and the majority of Saharan Africa shows an absolute decrease
incidents occur in the first year of life. in risk of 1.8 % which is a relative decrease
– Urinary tract infections are more common of between 38 and 66 % over 2 years, and
in male neonates than in females. in this population studies rate it cost
– There is an increased rate of urinary tract effective.
infections in uncircumcised males, espe- – Whether it is of benefit in developed coun-
cially in infants younger than 1 year. tries is undetermined.
– A study of infants with UTIs showed that 75 % – Circumcision only provides partial protec-
of those younger than 3 months were males tion from HIV and known methods should
and, of those, 95 % were uncircumcised. not replace HIV prevention.
– There is good evidence that circumcision – There are several mechanisms proposed to
reduces the incidence of urinary tract infec- explain the increased risk for STDs in
tions in boys under 2 years of age. uncircumcised males. These include:
– Recommending routine circumcision in all • A relatively nonkeratinized inner layer
newborn males is controversial and preven- of the prepuce which increases its sus-
tion of UTIs does not justify routine use of ceptibility to minor trauma during inter-
circumcision, however. course, allowing pathogens to penetrate
– Circumcision is most likely to benefit boys through microscopic abrasions.
who have a high risk of urinary tract infec- • The warm microclimate created by the
tions due to anatomical defects, and may be preputial pouch permits the microorgan-
used to treat recurrent UTIs. Circumcision isms to thrive in the smegma that col-
may reduce the risk of urinary tract infec- lects in this area.
tions through a decrease in the bacteria • The superficial skin layers of the
population. penis contain Langerhans cells, which
– Some children are at increased risk for are targeted by HIV; removing the
UTIs, such as children with neurogenic foreskin reduces the number of these
bladders who require clean, intermittent cells.
catheterization or children with poorly • When an uncircumcised penis is erect
emptying urinary tracts. Circumcision in during intercourse, any small tears on
these patients will facilitate the procedure the inner surface of the foreskin come
and reduce the risk of UTIs. into direct contact with the vaginal
• Management of sexually transmitted diseases walls, providing a pathway for
(STDs): transmission.
– There is strong evidence that circumcision – A significant two- to sevenfold increased
reduces the risk of HIV infection in hetero- risk of genital syphilis and chancroid
sexual men in high-risk populations. was reported in uncircumcised male
– The finding that circumcision significantly patients.
reduces female-to-male HIV transmission – Circumcision was found to be associated
in the HIV/AIDS epidemic sub-Saharan with lower rates of syphilis, chancroid and
Africa prompted the World Health possibly genital herpes.
Organization (WHO) to recommend cir- – Circumcision reduced the incidence of
cumcision as an additional method of con- HSV-2 (herpes simplex virus, type 2) infec-
trolling the spread of HIV. tions by 28 %.
22.6 Contraindications to Circumcision 485
• Management of human papillomavirus and – Childhood or adolescent circumcision is

cervical cancer: associated with a reduced risk of invasive
– Human papilloma virus (HPV) can be squamous cell carcinoma in particular.
oncogenic or nononcogenic. – There is an association between adult
– Nononcogenic HPV (genotypes 6 and 11) circumcision and an increased risk of
causes genital warts in men and women. invasive penile cancer; this is believed to be
– Oncogenic HPV (genotypes 16, 18, 31, and from men being circumcised as a treatment
33) are responsible for the great majority of for penile cancer or a condition that is a
cervical, vulvar, vaginal, anal, and penile precursor to cancer rather than a conse-
cancers. quence of circumcision itself.
– Circumcision significantly reduces the risk – The most important factor associated with
of penile HPV infection in men and of cer- the development of penile cancer is an
vical cancer in the female partners of male intact foreskin.
individuals who practice high-risk behav- – Penile cancer has been observed to be
iors such as engaging in sexual activity nearly eliminated in populations of males
with multiple partners. circumcised neonatally.
– Human papilloma virus (HPV) is the most – Jewish men (the great majority of them cir-
common sexually transmitted infection, cumcised) rarely develop penile cancer.
affecting both men and women. While – The other known major risk factor associ-
most infections are asymptomatic and are ated with penile cancer is phimosis.
cleared by the immune system, some types – Circumcision completely eliminates these
of the virus cause genital warts, and other risks.
types, if untreated, cause various forms of
cancer, including cervical cancer and
penile cancer. 22.6 Contraindications
– Genital warts and cervical cancer are the to Circumcision
two most common problems resulting from
HPV. • Prematurity
– Circumcised man are less likely to be • Chordee of the penis
infected with cancer-causing types of HPV. • Curvature of the penis
– Circumcision decreases the likelihood of • Hypospadias
multiple infections. • Epispadias
• Penile cancer: • Concealed or buried penis
– Circumcision has a protective effect against • Micropenis
the risks of penile cancer in men, and cervi- • Webbed penis
cal cancer in the female sexual partners of • Ambiguous genitalia
heterosexual men. • Bleeding diatheses
– Penile cancer is rare, with about 1 new case • In those with chordee of the penis, curvature
per 100,000 people per year in developed of the penis, micropenis, webbed penis and
countries, and higher incidence rates per concealed or buried penis, circumcision is
100,000 in sub-Saharan Africa (for exam- delayed and open classic surgical circumci-
ple, 1.6 in Zimbabwe, 2.7 in Uganda and sion is performed.
3.2 in Swaziland). • In those with Hypospadias, Epispadias and
– Penile cancer development can be Ambiguous genitalia, circumcision is done as
detected in the carcinoma in situ (CIS) part of the corrective surgery of these
cancerous precursor stage and at the more anomalies.
advanced invasive squamous cell carci- • Bleeding diatheses are not absolute contrain-
noma stage. dications for circumcision, and circumcisions
can be performed after preparation and opens the foreskin via the preputial ori-
treatment. The parents should be fully fice to reveal the glans underneath and
informed of the increased risks of ensures it is normal before bluntly sepa-
complications. rating the inner lining of the foreskin
• Circumcision is contraindicated in premature (preputial epithelium) from its attach-
infants and those who are not clinically stable ment to the glans.
and in good health. – The practitioner then places the circumci-
• A family history of hemophilia calls for a sion device (this sometimes requires a dor-
coagulation profile prior to circumcision. sal slit).
– Finally, the foreskin is excised.
• The AAP Task Force on Circumcision recom-
22.7 Surgical Procedure mends the use of environmental, nonpharma-
cological, and pharmacologic interventions to
• Open surgical circumcision (Figs. 22.4 and 22.5): reduce pain and distress during neonatal cir-
– This is usually performed under general cumcision. These interventions include:
anesthesia – The use of a sucrose pacifier
– Open surgical circumcision is performed – The use of paracetamol suppositories
for adults, older children or for those with – The use of EMLA cream (a mixture of pri-
associated anomalies of the penis such as locaine and lidocaine)
webbed penis, chordee and deviation of the – The use of penile nerve blocks (e.g. 0.5 %
penis. lidocaine without epinephrine)
– The amount of foreskin to be removed is • A ring block that consists of the circum-
determined and excised ferential subcutaneous injection of local
– The edges of the skin are sutured with anesthesia
absorbable sutures. • A dorsal penile block
– The end result is a cosmetically acceptable – Oral acetaminophen or paracetamol sup-
penis. positories provides adequate pain control
• For infant circumcision, devices such as the after neonatal circumcision.
Gomco clamp, Plastibel and Mogen clamp are – In patients who undergo formal surgical
commonly used. circumcisions in the operating room, cau-
• These follow the same basic procedure. dal blocks and dorsal penile blocks
– First, the amount of foreskin to be decrease the amount of pain medication
removed is estimated. The practitioner required after the procedure.
Figs. 22.4 and 22.5 Clinical photographs showing open surgical circumcision
22.7 Surgical Procedure 487
• The use of unipolar diathermy during circum- • Hypospadias is characterized by a deficient

cision should be avoided. foreskin ventrally while the dorsally the foreskin
• Prior to circumcision, it is important to deter- is well formed like a hood. The urethral opening
mine the presence of a normal glans and penis is placed ventrally (Figs. 22.8 and 22.9).
without any evidence of hypospadias, epispa- • A point of caution is in patients with mega
dias, chordee, or other anomalies. meatus variant of hypospadias. These patients
• Most cases of hypospadias or epispadias are have a normal well developed and complete
evident clinically and these should not be foreskin.
circumcised. • This variant is called, the mega meatus intact
• The foreskin in these patients can be used dur- prepuce (MIP) variant.
ing the repair of hypospadias or epispadias. • The urethral meatus in these patients is large
• Circumcision is part of the repair of these patients. (mega meatus) (Figs. 22.10 and 22.11).
• Epispadias is characterized by a deficient • These patients have a well-developed foreskin
foreskin and a dorsally placed urethral and the diagnosis of mega meatus is only
opening (Figs. 22.6 and 22.7). made at the time of circumcision.
Figs. 22.6 and 22.7 Clinical photographs showing epispadias. Note the dorsally located urethral opening
Figs. 22.8 and 22.9 Clinical photographs showing hypospadias. Note the deficient foreskin ventrally and the hood
like foreskin dorsally. Note also the abnormally located urethral opening on the ventral aspect of the penis
Figs. 22.10 and 22.11 Clinical photographs showing an infant with a megameatus. Note the normal looking foreskin.
Note also the abnormally large meatus
Figs. 22.12 and 22.13 Clinical photographs showing an infant with a foresking resembelling that of hypospadias but
a normally located urethral meatus
• Once the diagnosis is confirmed, circumcision • The bone cutter is rarely used nowadays
is abandoned and postponed to be done at the (Fig. 22.14).
time of repair of Mega meatus. • Plastibel Circumcision (Figs. 22.15, 22.16,
• Rarely, a deficient prepuce ventrally but a 22.17, 22.18, 22.19, 22.20, 22.21, 22.22,
normally situated meatus is seen (Figs. 22.12 22.23, 22.24, 22.25, 22.26, 22.27, and 22.28):
and 22.13). – First, the amount of foreskin to be removed
• The surgical procedure of male circumcision is estimated.
may involve one of various devices including: – The preputial orifice is widened with an
– The Circumplast artery forceps and the foreskin is opened.
– The Gomco clamp – This will reveal the glans underneath and
– The Plastibell ensure it is normal.
– The Mogen clamp – The inner lining of the foreskin (preputial
– The Shang ring epithelium) is bluntly separated from its
– The bone cutter attachment to the glans.
Fig. 22.14 A photograph

showing a bone cutter that is
used for circumcision
– The handle of the plastibel is snapped of

the plastibel.
– Sometimes, the frenulum band may need to
be broken or crushed and cut from the
corona near the urethra to ensure that the
glans can be freely and completely exposed.
This may nictitates the use of diathermy to
control bleeding. Only bipolar diathermy is
used and monopolar diathermy should be
Fig. 22.15 A clinical photograph showing plastibel cir-
avoid. There are small battery operated
cumcision. The size of the plastibel is large for the size of
the penis portable bipolar diathermy which can be
used for this purpose (Figs. 22.29, 22.30,
22.31, and 22.32).
– The area is cleaned and any smegma is – The tied suture causes ischemic necrosis of
removed. the remaining foreskin which falls down
– The size of the plastibel to be used is esti- together with the plastibel in 5–7 days
mated based on the size of the glans penis. (Figs. 22.33, 22.34, 22.35, and 22.36).
Improper plastibel size will give unsatis- – A plastibel that does not fall after 7 days
factory results (Fig. 22.15). should be removed.
– Plastibel come in different sizes: 1.1, 1.2, • There are also restrainers which can be used
1.3, 1.4, 1.5 and 1.7. during plastibel circumcision to control the
– A dorsal slit is made in the prepuce. This will movement of the infant (Fig. 22.37).
help and facilitate introducing the plastibel. • Circumplast circumcision (Fig. 22.38):
– To minimize bleeding from the dorsal slit – The procedure is similar to the plastibel
edges, each edge is held with an artery – The glans is freed
forceps. – The Circumplast is placed over the glans,
– The plastibel is placed over the glans and and the foreskin is placed over the
the edges of the dorsal slit are pulled by an Circumplast.
assistant who also pushes the plastibel and – A ligature is then tied firmly around the
keep it in place. foreskin and tightened into a groove in the
– A ligature is applied around the foreskin Circumplast to achieve hemostasis.
and firmly tied in an already made groove – The foreskin distal to the ligature is excised
in the plastibel. The pushed plastibel pro- and the handle is snapped off the
tect the glans penis. Circumplast device.
– Finally, the foreskin distal to the plastibel is – The Circumplast falls from the penis after
amputated. the wound has healed, typically in 4–6 days.
Fig. 22.16 A photograph showing the different sizes of plastibells
Figs. 22.17 and 22.18 Photographs showing the different shapes of plastibells
the foreskin may be cut away with a scalpel

• Gomco clamp circumcision (Fig. 22.39): from above the base plate.
– The foreskin is dorsally crushed with a
hemostat and then slit with scissors from • Mogen clamp circumcision (Figs. 22.40,
the tip to the coronal sulcus. 22.41, 22.42, and 22.43):
– The foreskin is drawn over the bell shaped – The foreskin is pulled dorsally with a
portion of the clamp and inserted through a straight hemostat, and lifted.
hole in the base of the clamp. – The Mogen clamp is then slid between the
– The clamp is tightened, “crushing the glans and hemostat, following the angle of
foreskin between the bell and the base the corona to “avoid removing excess skin
plate.” ventrally and to obtain a superior cosmetic
– The crushed blood vessels provide hemo- result” to Gomco or Plastibell circumcisions.
stasis. The flared bottom of the bell fits – The clamp is locked, and a scalpel is used to cut
tightly against the hole of the base plate, so the skin from the flat (upper) side of the clamp.
Figs. 22.19, 22.20, and 22.21 Clinical photographs showing an uncircumcised infant. The preputial opening is
dilated and opened
Figs. 22.22 and 22.23 Clinical photographs showing the dorsal slit and the introduced plastibell. The suture for tining
is already prepared
• The Shang ring circumcision (Figs. 22.44 and – The inner ring has a shallow groove on its outer
22.45): surface that is lined by a silicone band which
– The Shang Ring is a disposable MC device confers a non-bioreactive surface against which
invented by Mr. Jianzhong Shang in the outer ring sandwiches the foreskin.
China. – The outer ring consists of two halves that
– It is commercially available in China in are hinged together at one end.
32 sizes, ranging from 9 to 42 mm in – The outer ring is closed securely via a
diameter, for use with neonates to ratchet style closure.
adults. – Hemostasis provided by the locking rings
– The Shang Ring consists of two parts, an minimizes bleeding and removes the need
inner ring and an outer ring. for sutures.
Figs. 22.24, 22.25, 22.26, and 22.27 Clinical photographs showing the ligature being tied. Following this the handle
of the plastibell is broken
• Significant acute complications happen rarely,

occurring in about 1 in 500 newborn
procedures.
• Severe to catastrophic complications are suf-
ficiently rare that they are reported only as
individual case reports.
• Other possible complications include buried
penis, chordee, phimosis, skin bridges, ure-
thral fistulas, and meatal stenosis.
• These complications may be avoided with
Fig. 22.28 A clinical photograph showing the foreskin
proper technique.
being cut
• The circumcision procedure may carry the
risks of heightened pain response for new-
22.8 Complications borns and dissatisfaction with the result.
of Circumcision • Newborns that experience pain due to being
circumcised have different responses to vac-
• Neonatal circumcision is generally safe when cines given afterwards, with higher pain scores
done by an experienced practitioner. observed.
• The most common acute complications are • There are several complications known to be
bleeding, infection and the removal of either associated with neonatal circumcision.
too much or too little foreskin. • These complications include:
• These complications occur in approximately – Bleeding is the most common early com-
0.12 % of procedures. plication (Fig. 22.46)
• Minor complications are reported to occur in • This is commonly from the frenulum
3 % of procedures. blood vessels but can be also from the cut
• Complication rates are greater when the pro- edges of the foreskin or the dorsal vessels.
cedure is performed by an inexperienced • This is usually controlled with local
operator, in unsterile conditions, or when the hemostatic measures, such as pressure
child is at an older age. dressings.
22.8 Complications of Circumcision 493
Figs. 22.29 and 22.30 Clinical photographs showing the site of the frenulum where most bleeding occurs. These ves-
sels can be cauterized using pipolar diathermy
• Other complications described include the

followings:
– Recurrent phimosis
– Wound separation
– Penile torsion
– Concealed penis (Figs. 22.49 and 22.50)
– Unsatisfactory cosmetic appearance
(Figs. 22.51, 22.52, 22.53, and 22.54)
– Skin bridges (Figs. 22.55, 22.56, and
22.57)
– Urinary retention
– Meatitis
– Skin chordee (due to removal of excessive
Figs. 22.31 and 22.32 Photographs showing small por-
skin) (Fig. 22.58)
table cautery which can be used to control bleeding at the
time of circumcision – Inclusion cysts
– Retained Plastibel devices (Fig. 22.59)
– Incomplete circumcision (Fig. 22.60)
• Surgicele or other hemostatic agents can – Scalded skin syndrome
be applied also. A small piece of sur- – Necrotizing fasciitis
gicele can be inserted in the grove – Sepsis
between the glans penis and the plasti- – Meningitis
bel to control bleeding. – Urethral fistula
• If these measures fail, the patient must – Penile necrosis
be taken to the operating room for surgi- – Amputation of a portion of the glans penis
cal hemostasis and hematoma – Gangrene of the glans penis (Fig. 22.61)
evacuation. – Urethral fistula (Fig. 22.62)
– Infection is the second most common early • Sexual effects:
postoperative complication, but usually is – Circumcision does not appear to decrease
minor and easily managed with oral and the sensitivity of the penis, harm sexual
topical antibiotics. function or reduce sexual satisfaction.
– The most common long-term complication – A 2013 systematic review found that cir-
seen after circumcision is meatal stenosis cumcision did not appear to adversely
(Figs. 22.47 and 22.48). affect sexual desire, pain with intercourse,
Figs. 22.33 and 22.34 Clinical photographs showing the final stage of plastibel circumcision. The use of proper size
of plastibel is important
Fig. 22.37 A photograph of a restrainer that can be used

during plastibel circumcision
Fig. 22.38 A photograph showing circumplast
Fig. 22.35 and 22.36 Clinical photographs showing the • Psychological effects:
plastibel circumcision. Note the plastibel falling down – Behavioral effects have been observed fol-
lowing circumcision including changes in
premature ejaculation, time until ejacula- sleep patterns, irritability, changes in feed-
tion, erectile dysfunction or difficulties ing, and parental bonding.
with orgasm. – Some men who were involuntarily circum-
– Another 2013 systematic review reported no cised described their feelings about the
adverse effects of circumcision on sexual procedure using the terms “violation, tor-
function, sensitivity, sensation or satisfaction. ture, mutilation and sexual assault”.
Fig. 22.39 A photograph showing the Gomco device
Figs. 22.40, 22.41, 22.42, and 22.43 Photographs showing the Mogen clamp
OUTER
RING
INNER
RING
RATCHET
CLOSURE
Figs. 22.44 and 22.45 Photographs showing the Shang ring
Fig. 22.46 A clinical photograph showing bleeding fol-

lowing circumcision
Figs. 22.47 and 22.48 Clinical photographs showing meatal stenosis

Figs. 22.49 and 22.50 Clinical photographs showing concealed penis following circumcision
Figs. 22.51, 22.52, 22.53, and 22.54 Clinical photographs showing unsatisfactory cosmesis following circumcision
Figs. 22.55, 22.56, and 22.57 Clinical photographs showing skin bridges following circumcision
Fig. 22.59 A clinical photograph showing a retained

Fig. 22.58 A clinical photograph showing chordee plastibel. Note the associated swelling of the glans penis
Further Reading 499
Fig. 22.60 A clinical photograph showing incomplete

circumcision
Fig. 22.62 A clinical photograph showing a urethral fis-

tula following circumcision
2. Bossio JA, Pukall CF, Steele S. A review of the cur-

rent state of the male circumcision literature. J Sex
Med. 2014;11:2847–64.
3. Doyle SM, Kahn JG, Hosang N, Carroll PR. The
impact of male circumcision on HIV transmission.
J Urol. 2010;183(1):21–6.
4. Lannon CM, Bailey AGB, Fleischman AR.
Circumcision policy statement. American Academy
of Pediatrics. Task Force on Circumcision. Pediatrics.
1999;103(3):686–93.
Fig. 22.61 A clinical photograph showing gangrenous 5. Tobian AA, Serwadda D, Quinn TC, Kigozi G, Gravitt
glans penis following circumcision PE, Laeyendecker O, et al. Male circumcision for the
prevention of HSV-2 and HPV infections and syphilis.
N Engl J Med. 2009;360(13):1298–309.
6. Weiss HA, Quigley MA, Hayes RJ. Male circumci-
sion and risk of HIV infection in sub-Saharan Africa:
Further Reading a systematic review and meta-analysis. AIDS.
2000;14(15):2361–70.
1. Alanis MC, Lucidi RS. Neonatal circumcision: a 7. Wiswell TE, Hachey WE. Urinary tract infections and
review of the world’s oldest and most controversial the uncircumcised state: an update. Clin Pediatr
operation. Obstet Gynecol Surv. 2004;59(5):379–95. (Phila). 1993;32(3):130–4.
Priapism in Children
23
23.1 Introduction • At least one-third of male adults with SCD

present with priapism at some point, usually
• Priapism is defined as a prolonged, non- beginning in school age.
physiologic, sustained and painful erection. • Nearly one-fourth of priapism in patients with
– It is not provoked by sexual stimulation or SCD present during the prepubertal period.
arousal • The mean age for the onset of priapism in
– It persists after ejaculation and orgasm. patients with SCD is 11 years.
• Priapism is an uncommon condition that needs • In patients with SCD, priapism rarely present
to be recognized early and immediate medical for the first time after the third decade of life.
attention is important. • In children nearly all cases of priapism are
• It is considered a true medical and urologic secondary to sickle cell disease or trauma.
emergency, and early intervention allows the • Priapism in childhood commonly presents as
best chance for functional recovery. a complication of sickle cell disease (SCD)
• Prompt diagnosis and treatment of priapism (Figs. 23.1 and 23.2).
are important to prevent tissue damage that • The frequency of priapism in children with
could result in the inability to get or maintain SCD varies between 2 and 6 %.
an erection (erectile dysfunction). • Priapism normally involves the two corpora
• Such a prolonged erection causes physiologi- cavernosa and spares the corpora spongiosum.
cal changes by 6 h, cellular damage by 24 h, • Priapism as a complication of SCD can cause
and fibrosis by 36 h, resulting in permanent persistent impotence, erectile dysfunction and
erectile dysfunction. behavioral sexual problems (Figs. 23.3).
• Priapism can present in childhood and • A prior history of priapism makes these
adolescence. patients fear any sexual activities as these may
• It is most commonly seen between ages 5 and induce an episode of priapism.
10 in boys and ages 20 and 50 in men. • In patients with SCD:
• Nocturnal episodes of priapism are more – Priapism was first reported in SCD patients
frequent. in 1934.
• Priapism is frequently idiopathic in etiology – The most frequent form of priapism in
but it is a known complication of a number of patients with SCD is recurrent self-limited
important medical conditions and pharmaco- short episodes (stuttering priapism)
logic agents. – Acute episodes of priapism are defined as
• More than one-fourth of priapism episodes are painful erection and/or persisting more
caused by sickle cell disease (SCD). than 4–6 h.

502 23 Priapism in Children
Figs. 23.1 and 23.2 Clinical photographs showing priapism in a child
– Approximately two-third of patients pre- • Low-flow priapism is by far the most common
senting with an acute attack of priapism type.
report previous intermittent episodes. • High-flow priapism is rare and is usually
• Priapism is classified into high or low blood a result of blunt trauma to the corpora
flow. cavernosus resulting in arteriovenous
• It is important to differentiate between the two fistula.
types as this important in terms of treatment • The treatment for high-flow priapism is sur-
and prognosis. gical identification and obliteration of
• High flow priapism (Nonischemic priapism) fistulas.
is characterized by an increase of arterial sup- • Causes of low-flow priapism include the
ply to the corpora cavernosa while the venous followings:
drainage remains normal. – Idiopathic
• Low flow priapism (Ischemic priapism) is – Hematologic (e.g. sickle cell, leukemia)
characterized by loss of vascular regulation – Pharmacologic adverse effects (e.g. psy-
and the venous drainage is impaired, presum- chiatric medications)
ably as a consequence of vascular blockage by – Therapeutic medications (e.g. oral erectile
deformed red blood cells. medications, intracavernous injections)
• It is estimated that more than 80 % of patients – Neoplastic
with SCD have low flow priapism and occa- – Others (e.g. surgical, traumatic, neuro-
sionally it may be high flow priapism. genic, infectious)
• The urethra runs within the corpora

spongiosum.
• The erectile tissue within the corpora con-
tains arteries, nerves, muscle fibers, and
venous sinuses lined with flat endothelial
cells, and it fills the space of the corpora
cavernosa.
• The cut surface of the corpora cavernosa looks
like a sponge. There is a thin layer of areolar
tissue that separates this tissue from the tunica
albuginea.
• Blood flow to the corpora cavernosa is via the
paired deep arteries of the penis (cavernosal
arteries), which run near the center of each
corpora cavernosa.
• Normally, erection occurs in response to phys-
ical or psychological stimulation.
• Erection is the result of smooth-muscle relax-
ation and increased arterial flow into the cor-
pora cavernosa, causing engorgement and
rigidity.
• Corporeal relaxation causes external pressure
on the emissary veins exiting the tunica albu-
ginea, trapping blood in the penis and causing
Fig. 23.3 Clinical photograph of an adult with priapism erection.
• Engorgement of the corpora cavernosa com-
presses the venous outflow tracts (i.e. subtuni-
• Management of low flow priapism should cal venules), trapping blood within the corpora
achieve resolution as promptly as possible. cavernosa.
• Early intervention allows the best chance for • Erection is induced by the parasympathetic
functional recovery and minimize the autonomic nervous system.
sequelae. • This stimulation causes penile blood vessels
• Treatment of low-flow priapism should prog- to relax and expand, increasing blood flow to
ress in a stepwise fashion, starting with thera- the spongy tissues in the penis.
peutic aspiration, with or without irrigation of • The major neurotransmitter that controls erec-
the corpora. If this fails, intracavernous injection is nitric oxide, which is secreted by the
tion of sympathomimetic drugs is the next step. endothelium that lines the corpora cavernosa.
• Rapid resolution of ischaemic (low flow) pria- These events occur in both normal and patho-
pism prevents permanent cavernosal structural logic erections.
damage and is associated with improved prog- • Sexual stimulation causes the release of nitric
nosis for potency later in life. oxide (NO) via stimulation of noradrenergic
norcholinergic neurons, provoking a local
increase of cyclic GMP (cGMP) by the activa-
23.2 Pathophysiology tion of guanylate-cyclase.
• NO-activated intracellular guanylate cyclase,
• The penis is made up of three corporeal erectile converting guanosine triphosphate (GTP) to
tissues, two corpora cavernosa on the dorsum cyclic guanosine monophosphate (cGMP),
of the penis and corpora spongiosum ventrally. causes relaxation of cavernosal arteries and
increased penile blood flow, resulting in • Prolonged low-flow priapism leads to a

erection. painful ischemic state, which can cause fibro-
• Cyclic GMP then enhances the cellular efflux sis of the corporeal smooth muscle and caver-
of calcium and the relaxation of smooth mus- nosal artery thrombosis. The degree of
cle of efferent arteries and of the corpora cav- ischemia is a function of the number of emis-
ernosa itself. This will lead to an increase in sary veins involved and the duration of
the afferent blood flow. occlusion.
• The draining venules which are located • Light-microscopy studies conducted early
between the corpora cavernosa, are passively demonstrated that corporeal tissue becomes
compressed by the rigid congested corpora thickened, edematous, and fibrotic after days
and as a result blood accumulates. of priapism.
• Consequently, the blood-filled penis becomes • Further studies with electron microscopy have
erect. demonstrated trabecular interstitial edema
• The erection process ends by ejaculation and after 12 h of priapism and destruction of sinu-
orgasm. soidal endothelium, exposure of the basement
• As a result of this, signals are sent to the sym- membrane, and thrombocyte adherence after
pathetic nervous system which determines the 24 h of priapism. At 48 h, thrombi were evi-
vasoconstriction of the efferent arteries of the dent in the sinusoidal spaces and smooth-
corpora cavernosa, leading to reduction in the muscle cell.
blood inflow. • Histopathologic findings varied from necrosis
• This will lead to an increase in venous drain- to fibroblast-like cell transformation. Priapism
age mechanisms and detumescence results. for longer than 24 h is associated with perma-
The blood flows out of the penile blood ves- nent impotence.
sels, and the penis returns to its nonrigid • High-flow priapism is the result of uncon-
(flaccid) state. trolled arterial inflow from a fistula between
• Pathophysiologically, priapism can be of the cavernosal artery and the corpus caverno-
either a low-flow (ischemic) or a high-flow sum. This is generally secondary to blunt or
(nonischemic) type. penetrating injury to the penis or perineum
• Low-flow priapism, which is by far the most causing rupture of a cavernous artery. It is usu-
common type, results from failure of venous ally not painful.
outflow, whereas high-flow priapism results • In priapism, the corpus spongiosum and glans
from uncontrolled arterial inflow. penis are typically not engorged.
• Clinically, differentiation of low-flow from • Ischemic (low flow) priapism can cause seri-
high-flow priapism is critical, because ous complications.
treatment and prognosis for each is – The blood trapped in the penis is deprived
different. of oxygen.
• Low-flow priapism may be due to any of the – When an erection lasts for longer than
following: 4 h, this oxygen-poor blood can begin
– An excessive release of neurotransmitters to damage or destroy tissues in the
– Blockage of draining venules (e.g., mechan- penis.
ical interference in sickle cell crisis, leuke- • As a result, untreated priapism may cause:
mia, or excessive use of intravenous – Erectile dysfunction, the inability of the
parenteral lipids) penis to become or stay erect with sexual
– Paralysis of the intrinsic detumescence arousal
mechanism – Disfigurement of the penis
– Prolonged relaxation of the intracavernous • Sickle cell anemia is the most common
smooth muscles (most often caused by the cause of priapism in boys (Figs. 23.4 and
use of exogenous smooth-muscle relaxants 23.5).
such as injectable intracavernosal prosta- • Priapism can be primary or idiopathic and
glandin E1) secondary to other factors.
23.3 Etiology 505
Figs. 23.4 and 23.5 Clinical photograph showing priapism in two children with sickle cell disease
• Factors that can contribute to priapism include 23.3 Etiology

the following:
– Blood disorders including: • Priapism can be idiopathic or can be second-
• Sickle cell anemia ary to a variety of diseases, conditions, or
• Leukemia medications.
– Medications including: • In the United States, the most common cause
• Oral medications used to treat erectile of priapism in the adult population involves
dysfunction, such as sildenafil agents used to treat erectile dysfunction.
(Viagra), tadalafil (Cialis) and varde- • Internationally, most cases are idiopathic.
nafil (Levitra) • The most common cause of priapism in the
• Drugs injected directly into the penis to treat pediatric population is sickle cell disease
erectile dysfunction, such as papaverine (SCD), which is responsible for more than
• Antidepressants, such as fluoxetine 65 % of cases.
(Prozac) and bupropion (Wellbutrin) • Leukemia, trauma, and idiopathic causes are
• Drugs used to treat psychotic disorders, the causes in 10 % of patients.
such as risperidone (Risperdal) and • Pharmacologically induced priapism is the
olanzapine (Zyprexa) etiology in 5 % of children.
• Anticoagulant, such as warfarin • Among the secondary causes of low-flow pri-
(Coumadin) and heparin apism are the followings:
• Alcohol and drug abuse (marijuana or – Sickle cell anemia – One study found that,
cocaine) in unscreened children with SCD, pria-
– Trauma or injury to the genitals, pelvis or pism was the first presentation in 0.5 % of
the perineum is a cause of nonischemic cases.
(high flow) priapism – Thalassemia
– Other causes of priapism include: – Dialysis
• Spinal cord injury – Vasculitis
• Blood clots – Fat embolism (from multiple long-bone
• Poisonous venom, such as venom from fractures or intravenous infusion of lipids
scorpions or black widow spiders as part of total parenteral nutrition)
PHYSICAL OR PSYCHOLOGICAL STIMULATION
PARASYMPATHETIC SYSTEM
RELEASE OF NITRIC OXIDE
ACTIVATION OF GUANYLATE CYCLASE
GMP cGMP
CELLULAR Ca EXTRCELLULAR Ca
VASODILATATION
ERECTION
– Neurologic diseases that can result in low- • Psychotropics – Phenothiazine, butyro-

flow priapism include the following: phenones (e.g. haloperidol), perphen-
• Spinal cord stenosis (i.e. trauma to the azine, trazodone, selective serotonin
medulla) reuptake inhibitors (e.g. fluoxetine, ser-
• Autonomic neuropathy and cauda traline, citalopram) [3]
equina compression • Anticoagulants – Heparin, warfarin
– Neoplastic disease (metastatic to the penis (during rebound hypercoagulable states)
or obstructive to venous outflow) that can • Recreational drugs – Cocaine
result in low-flow priapism include the • Hormones – Gonadotropin-releasing
following: hormone (GnRH), tamoxifen, testoster-
• Prostate cancer one, androstenedione for athletic perfor-
• Bladder cancer (highest risk) mance enhancement
• Hematologic cancer (leukemia) • Herbal medicine – Ginkgo biloba with
• Renal carcinoma concurrent use of antipsychotic agents
• Melanoma • Miscellaneous agents – Metoclopramide,
– Pharmacologic causes of low-flow pria- omeprazole, penile injection of cocaine,
pism include the following: epidural infusion of morphine and
• Intracavernosal agents – Papaverine, bupivacaine
phentolamine, prostaglandin E1 • Only rare case reports have associated
• Intraurethral pellets (i.e. medicated ure- phosphodiesterase-5 enzyme inhibitors
thral system for erection with intracav- such as sildenafil with priapism. In fact,
ernosal prostaglandin E1) several reports suggest sildenafil as a
• Antihypertensives – Ganglion-blocking means to treat priapism and as a possi-
agents (e.g. guanethidine), arterial vasodi- ble means of preventing full-blown epi-
lators (e.g. hydralazine), alpha-antagonists sodes in patients with sickle cell
(e.g. prazosin), calcium channel blockers disease.
23.4 Classification of Priapism 507
• High-flow priapism may result from the fol- corpora cavernosa while the venous
lowing forms of genitourinary trauma: drainage remains normal.
– Straddle injury • An adequate arterial flow and well-
– Intracavernous injections resulting in direct oxygenated corpora
cavernosal artery injury • The prognosis is better, and secondary
• Rare causes of priapism include the impotence is rare (<20 %).
following: • In children high flow priapism is typi-
– Amyloidosis (massive amyloid infiltration) cally caused by post-traumatic arterio-
– Gout (one case report) cavernosal fistula (from penile, perineal
– Carbon monoxide poisoning or pelvic trauma), and generally mani-
– Malaria fests several days after the trauma.
– Black widow spider bites • Evidence of blunt or penetrating injury
– Asplenia to the penis or perineum especially
– Fabry disease (rare association, occasion- straddle injury is usually the initiating
ally noted to be priapism of the high-flow event.
type) • It can also be caused by:
– Vigorous sexual activity – Intracavernosal injections of vasoac-
– Mycoplasma pneumoniae infection (mech- tive agents
anism is thought to be a hypercoagulable – Scorpion or snake bites
state induced by the infection) – Substance abuse (mainly cocaine,
which can cause high or low output
priapism)
23.4 Classification of Priapism – Therapeutic drugs (especially psy-
chiatric medications with autonomic
• Priapism is a sustained painful erection of the nervous system effects
penis often nocturnal or starting in the early – Infectious diseases or tumors
hours of the morning. • Low flow priapism (ischemic):
• Priapism develops when there is excess arte- – This is the commonest type
rial inflow to the penis or when there is persis- – Low flow priapism is characterized by loss
tent venous outflow obstruction to the penis. of vascular regulation.
• Priapism is classified into two main types: – Venous drainage is impaired, presumably
– High flow arterial priapism. This is also as a consequence of vascular blockage by
called non-ischemic priapism. deformed red blood cells.
– Low flow priapism. This is also called isch- – This is the classic type seen in patients with
emic priapism. SCD where there is stasis leading to
• High flow (non-ischemic) priapism: hypoxia and acidosis of venous blood in a
– This is usually seen following trauma caus- normally erected penis. This will lead to
ing injury to the cavernosal artery. sickling of RBCs within the corpora caver-
– This type of priapism is generally not pain- nosa venous sinusoids, venous outflow
ful and may manifest in an episodic obstruction and engorgement of the cor-
manner. pora cavernosa. The corpora spongiosa and
– The penis in high flow priapism is neither glans of the penis are spared.
fully rigid nor painful and does not require – The corpora cavernosa becomes rigid and
an emergency treatment. tender to palpation.
– Characteristics of high-flow priapism – This may be further complicated as the
include the following: fixed resistance maintained by the adventi-
• High flow priapism is characterized by tia of the corpora cavernosa causes a com-
an increase of arterial supply to the partment syndrome.
– Low-flow priapism is generally painful, 23.5 Clinical Features

although the pain may disappear with pro-
longed priapism. • Priapism causes abnormally persistent erec-
– Characteristic features of low-flow pria- tions not related to sexual stimulation.
pism include the following: • Priapism symptoms may vary depending on
• Rigid erection the type of priapism.
• Ischemic corpora as indicated by dark • There are two main types of priapism: isch-
blood upon corporeal aspiration emic and nonischemic priapism.
• No evidence of trauma • Ischemic priapism:
– Low flow priapism is considered a medical – Ischemic, also called low-flow, priapism is
and surgical emergency and priapism the result of blood stasis in the penis.
should be resolved within 6 h of the onset – It’s the more common type of priapism.
of the episode to minimize the sequelae. – Low-flow, ischemic-type priapism is gen-
– In addition to SCD, low flow priapism can erally painful, although the pain may dis-
be caused other hematologic diseases with appear with prolonged priapism.
hypercoagulability or hyperviscosity such – It is characterized by ischemic corpora, as
as leukemia’s and several drugs. indicated by dark blood upon corporeal
• It is important to differentiate between these aspiration; and no evidence of trauma
two types as the management and prognosis – The history may reveal an underlying cause
are different. – Stuttering priapism is unwanted erection
• The two types of priapism can be differenti- off and on for several hours.
ated using color duplex Doppler ultrasonogra- – Signs and symptoms include:
phy and analysis of blood aspirated from the • Unwanted erection lasting more than 4 h
corpora cavernosa. • It is characterized by a rigid, painful
– Color Doppler ultrasonography measures erection
blood flow. This typically show little or no • Rigid penile shaft, but usually soft glans
blood flow in the cavernosal arteries in of penis
those with low flow priapism. • Usually painful or tender penis
– Analysis of blood aspirated from the cor- • Nonischemic priapism:
pora cavernosa is done at the time of aspi- – Nonischemic, or high-flow, priapism
ration and irrigation. occurs when too much blood flows into the
– In patients with high flow priapism, the penis.
aspirated blood: – This type of priapism is associated with
• Is bright red blunt or penetrating injury to the perineum.
• Has a pO2 >90 % mmHg, pCO2 It may manifest in an episodic manner.
<40 mmHg and a pH of approximately – Nonischemic priapism is usually painless.
7.40. – Signs and symptoms include:
– In patients with low flow priapism, the • Unwanted erection lasting at least 4 h
aspirated blood: • Erect but not rigid penile shaft
• Is dark in color • Patients with high-flow priapism typi-
• Has a pO2 <30 mmHg, pCO2 >60 mmHg cally have a history of blunt or penetrat-
and a pH <7.25. ing trauma to the penis or perineum,
• Priapism is also classified into two types: resulting in a fistula between a caverno-
– Stuttering priapism: This lasts 2–4 h, sal artery and the corpus cavernosum.
often recurrent and may precede a severe • Clinically, high-flow priapism is charac-
attack. terized by a painless erection; tumes-
– Acute (Severe) priapism: This lasts longer cence is typically less marked than in
than 4 h and can result in impotence. low-flow priapism.
• The presence of bright red blood dur- 23.6 Investigations

ing aspiration is a helpful but not
pathognomonic finding of high-flow • A complete blood cell count (CBC) should be
priapism. performed to determine whether the patient
• Penile blood gases findings approximate has anemia, leukocytosis, or thrombocytosis.
normal arterial values. • Patients with sickle cell disease should have a
• Penile duplex ultrasonography with CBC and a reticulocyte count.
angiographic confirmation helps to • If sickle cell status is unknown, a hemoglobin
identify and locate these fistulae. electrophoresis should be done.
• Patients with priapism report a persistent • Patients with sickle cell disease may also need
erection. a blood type and screen performed in case
• The physical examination detects an erection blood transfusion or exchange is necessary.
restricted to the corpora cavernosa. The spon- • Urinalysis and urine culture
giosum and the glans remain flaccid, except • Measurement of plasma thromboplastin or
for the rare cases of tricorporal priapism. activated partial thromboplastin time to deter-
• Because of the lack of involvement of the peri- mine coagulation status may be useful, as pri-
urethral spongiosum, there are normally no apism may require surgical intervention if
micturating problems. medical treatment fails.
• Accompanying symptoms depend on the type • Penile blood gas results allow differentiation
of priapism and the duration of engorgement. between high- and low-flow priapism.
• Penile priapism generally involves only the – Low-flow priapism, penile blood gases
paired corpora cavernosa, with the glans and findings:
corpora spongiosum remaining flaccid or • The blood will be dark
softly distended without rigidity. • Acidotic (pH <7.0)
• In high flow priapism the erection is less rigid • Hypercarbonic (PCO >60 mmHg)
and the penis is pink and pulsatile. • Hypoxemic (PO2 <30 mmHg)
• There can be signs of trauma (hematomas, • Variations in these values depend on the
bruises). duration of priapism.
• It may be possible to resolve the erection com- – High-flow priapism penile blood gases
pressing the arteriovenous fistula feeder ves- findings:
sel, but the erection will recur immediately • The blood will be red
after the compression is withdrawn. • Alkalotic (pH >7.0)
• In low flow priapism the penis is rigid, • Normally oxygenated (pO2 >60 mmHg)
extremely painful and seems ischemic: it does • pCO2 <70 mmHg
not pulse, is pale or grayish and cold. These • Color-flow penile Doppler imaging is cur-
manifestations are more evident after the epi- rently the study of choice to differentiate high-
sode has evolved for at least 4 h. flow from low-flow priapism. In patients with
• In young children, the presence of the Piesis high-flow priapism, ultrasonography can help
sign (prompt detumescence upon perineal identify and locate fistulas.
compression with the examiner’s thumb) indi- • In patients with high-flow priapism, selective
cates high-flow priapism. penile angiography may be required in order to
• To provide appropriate treatment, physicians identify the site of the fistula, or to confirm the
must differentiate between low-flow and high- location of a fistula identified by ultrasound.
flow priapism. This is accomplished by taking The fistula can then be closed by embolization.
a thorough history, performing a careful phys- • Perform chest radiography or computed
ical examination, and measuring the oxygen tomography (CT) scanning if the history is
content of blood within the corpora cavernosa consistent with a malignant or metastatic
by penile blood gas analysis. condition.
• Use of scintigraphy has been proposed to dif- • The European Association of Urology guide-
ferentiate low (decreased uptake, “cold” CC) lines on the diagnosis and treatment of pria-
from high flow cases, but the limited availabil- pism include:
ity of the test, its low specificity and sensitiv- – Interventions for ischemic priapism, which
ity and the lack of a comparative or gold is an emergency condition, should begin
standard has limited its use. within 4–6 h and include decompression of
• Doppler ultrasound is more useful for high the corpora cavernosa by aspiration and
flow cases, to identify an arteriovenous fistula intracavernous injection of sympathomi-
supplying the erection. metic drugs
• Cavernosography is rarely used, because – When conservative management for isch-
blood analysis is adequate and less emic priapism fails, surgical treatment is
aggressive. recommended
• Arteriography of the internal pudendal artery – For patients with long-lasting priapism,
has some limited use in high flow cases in immediate implantation of a prosthesis
which there is an intention to treat by emboli- should be considered
zation or surgery. – For arterial priapism, which is not an emer-
gency, selective embolization has high suc-
cess rates
23.7 Management – The main therapeutic goal for stuttering
priapism is prevention of future episodes,
• Appropriate treatment of priapism varies, which may be achieved pharmacologically
depending on whether the patient has low- (although information on the efficacy of
flow or high-flow priapism. such treatment is limited)
• Most priapism cases are the low-flow isch- – Prehospital Care
emic type. • Prehospital Care:
• Treatment of low-flow priapism should prog- – Any patient who has an erection for longer
ress in a stepwise fashion, starting with thera- than 4 h, especially if he has a predisposing
peutic aspiration, with or without irrigation, or illness (e.g., sickle cell disease) should
intracavernous injection of a sympathomi- receive therapy for priapism
metic agent. – Most cases, if seen early enough in their
• Treatment of high-flow priapism focuses on course, respond to conservative measures.
identification and obliteration of fistulas. • The use of ice packs to the perineum
• In patients with priapism secondary to other and penis
disorders, attempt to treat the underlying con- • Ask the patient to walk upstairs. The lat-
dition whenever possible. ter strategy is thought to work via an
• Treatment for priapism secondary to sickle arterial steal phenomenon.
cell disease includes hydration, alkalization, • External perineal compression may also
analgesia, and oxygenation to prevent fur- be a useful temporizing measure.
ther sickling. Hypertransfusion and/or • Low-Flow Priapism
exchange transfusions may be required to – Treatment should progress in a stepwise
increase hemoglobin concentration to higher fashion, accompanied by supportive care
than 10 % and decrease hemoglobin S to less and the identification and treatment of
than 30 %. reversible causes.
• At least 50 % of patients with priapism have – Intracavernosal phenylephrine (Neo-
persistent impotence, either because of the Synephrine) is the drug of choice and first-
priapism event or its treatment. line treatment of low-flow priapism
23.7 Management 511
because the drug has almost pure alpha- • Because multiple communications exist
agonist effects and minimal beta activity. from one corpus to the other, aspiration
– In short-term priapism (<6 h), especially usually is required on one side only.
drug-induced cases, intracavernosal injec- • If initial aspiration of the corpus caver-
tion of phenylephrine alone may result in nosum reveals bright red blood rather
detumescence. than dark venous blood, consider an
– Some studies suggest that terbutaline arterial cause for priapism and treat as
orally, at a dose of 5–10 mg, followed by for high-flow cases.
another 5–10 mg 15 min later, if required, • Aspiration alone has a success rate of
produces resolution in about one third of around 30 %.
patients. • If this procedure is not successful, phen-
– Oral pseudoephedrine, 60–120 mg orally ylephrine, epinephrine, or methylene
has also been suggested as a potential ther- blue may be instilled into the corpus
apy due to its alpha-agonist effect. The cavernosa.
exact efficacy of this medication orally is • For the injection, use a mixture of 1
unknown. ampule of phenylephrine (1 mL:
– Oral medications may be a reasonable 1,000 mcg) and dilute it with an addi-
treatment option to use while preparing for tional 9 mL of normal saline.
aspiration/injection. If no resolution occurs • Using a 29-gauge needle, inject 0.3–
within 30 min, injection therapy is required. 0.5 mL into the corpora cavernosa, wait-
– Aspiration/injection of the corpus ing 10–15 min between injections.
cavernosum: • Monitor vital signs and apply compres-
• First perform a penile nerve block. sion to the area of injection to help pre-
• Inject around the entire base of the vent hematoma formation.
penile shaft with 1 % lidocaine without • If phenylephrine is not available, epi-
epinephrine or bupivacaine without nephrine can be used. However, epi-
epinephrine. nephrine has more adverse effects and is
• Providing anesthesia will increase considered second-line treatment.
patient comfort and improve patient Another second-line treatment is instil-
cooperation with the sometimes-painful lation of methylene blue.
penile aspiration procedure. • Alternatively, the corpora cavernosa can
• After anesthesia is ensured, use a 19-gauge be irrigated with a diluted solution of
needle attached to a large syringe to punc- phenylephrine. A diluted solution can
ture the corpus cavernosum. The needle be infused 10–20 mL at a time.
should be inserted through the shaft of the • If aspiration or injection is successful in
penis laterally to avoid the corpus spon- producing detumescence, place an elas-
giosum and urethra ventrally and the neu- tic bandage around the shaft of the penis
rovascular bundle dorsally. to ensure continued emptying of the cor-
• Aspirate 20–30 mL of blood from either pora and to compress the puncture site.
the 2-o’clock or 10-o’clock position • High-Flow Priapism:
while milking the shaft. – Acutely, observation alone may be sufficient
• Aspiration may be difficult because of for high-flow priapism, because many cases
the sluggish blood within the corpus resolve spontaneously, and even with pro-
cavernosum. longed priapism these patients are unlikely
• Saline irrigation and repeated aspira- to experience significant pathological dam-
tions may improve flow dynamics. age or impaired erectile function.
– Compression therapy may be successful in – Immediate insertion of a penile prosthesis

certain cases, especially children; continu- in patients with prolonged low-flow pria-
ous compression may be maintained with a pism is simple and maintains penile
strap-on dressing. length. This may be offered to patients at
– Selective angiography with subsequent initial presentation, as the complication
embolization of the offending vessel has rate is low and the subsequent outcome
been shown to be effective with few long- excellent.
term complications in some studies.
– Selective arterial embolization can be done
using autologous blood clot, gelatin
sponge, microcoils, or chemicals. 23.8 Prognosis
– Patients who do not respond to more con-
servative measures may benefit from this • The prognosis depends on the duration of
approach. symptoms, the patient’s age, and the underly-
– Surgical ligation of the fistula may be required. ing pathology.
However, potential complications of this pro- • The duration of symptoms is the single most
cedure include long-term impotence. important factor affecting outcome.
• Surgical Care: • A Scandinavian study reported that 92 % of
– A transglanular-to-corpus cavernosal scal- patients with priapism for less than 24 h
pel or needle-core biopsy (Ebbehoj or remained potent, while only 22 % of patients
Winter technique) is the first reasonable with priapism that lasted longer than 7 days
approach for refractory priapism. remained potent.
– A unilateral shunt is often effective. • All patients with priapism should be warned
– Bilateral shunts are used only if necessary about the long-term risk of erectile
(usually apparent after 10 min). dysfunction.
– The El-Ghorab procedure is a more aggres- • In general, low flow (ischemic) priapism poses
sive open surgical cavernosal shunt and is a higher risk of impotence than high-flow arte-
indicated if the Winter shunt fails. rial priapism.
– Quackel shunts are cavernosal-spongiosum • Sickle cell disease patients appears to be par-
shunts (unilateral or bilateral) and are per- ticularly at increased risk.
formed via a perineal approach. Such • A study by Anele and Burnett found that
shunts are rarely effective if a more distal patients with sickle cell disease who experi-
shunt has already failed (e.g., El-Ghorab ence even minor episodes of recurrent isch-
procedure) because thrombosis of the cor- emic priapism are five times more likely to
pora is usually already present. develop erectile dysfunction compared with
– A Grayhack shunt is a cavernosal- non–sickle cell patients.
saphenous vein shunt (rarely necessary or • Infection can complicate priapism.
indicated). Proximal cavernosal-saphenous • Patients must understand that a poor outcome
shunt (Grayhack shunt) surgically connects is possible despite appropriate and timely
the proximal corpora cavernosum to the management.
saphenous vein. • Stuttering priapism requires careful counsel-
– Prolonged low-flow priapism results in a ling for episodic management.
variable degree of cavernosal fibrosis and a • Chronic prophylaxis may be obtained using
subsequent loss of penile length. α-adrenergic sympathomimetics, phosphodi-
– The delayed insertion of a penile prosthesis esterase type 5 inhibitors and, in sickle cell
can be difficult, with high complication rates. disease, hydroxyurea.
23.9 Priapism and Sickle Cell Disease 513
23.9 Priapism and Sickle Cell • Although the mechanism that causes low-flow
Disease priapism in patients with SCD is not fully
understood, it may be caused by the sickling
23.9.1 Introduction of red blood cells in the sinusoids of the cor-
pora cavernosa during normal erection. This
• Priapism is defined as a prolonged sustained sickling leads to venous stasis, resulting in
erection, often accompanied by pain and decreased local oxygen tension and pH, which
swelling, and not associated with sexual further potentiate stasis, sickling, and second-
desire. ary priapism.
• Priapism is one of the serious complications • This type of priapism is considered a medical
of sickle cell disease (SCD) and if left and surgical emergency because, if it is left
untreated, irreversible fibrosis and impotency untreated, irreversible cellular damage and
may occur (Figs. 23.6 and 23.7). fibrosis may occur, resulting in long term
• The exact incidence of priapism in patients impotence.
with sickle cell disease is not known but it was • There are two types of priapism:
thought to be present in 5–10 % of the patients. – Low flow priapism (Ischemic priapism)
• In patients with SCD, the probability of hav- – High flow priapism (Nonischemic priapism)
ing at least one episode of priapism by age 20 • Low-flow priapism tends to be much more
was reported to be 89 %. common in patients with SCD.
• Approximately 27 % of patients with SCD • High-flow priapism is thought to be secondary
reported having at least one episode of priapism. to unregulated arterial inflow, leading to pro-
• The mean age of patients when they had their longed but painless erection. It is more com-
first episode was 12 years, and the majority of monly associated with penile trauma, but it
episodes were nocturnal. has been reported in patients with SCD.
• The frequency of priapism in adults ranges • High-flow priapism tends to require arterial
from 30 to 45 %. embolization or ligation to produce detumes-
• There also appears to be bimodal peak fre- cence, while low-flow priapism tends to
quencies for patients 5- to 13-years old and respond to pharmacologic agents and or
21- to 29-years old. surgery.
Figs. 23.6 and 23.7 Clinical photographs showing priapism in a child with sickle cell disease
• Priapism in patients with SCD can be acute,

lasting for hours or days, or stuttering, occur-
ring in an intermittent pattern, lasting for a
few minutes to up to 3 h and generally resolv-
ing on its own.
23.9.2 Epidemiology
• Priapism has been described at nearly all ages, Fig. 23.8 A clinical photograph showing low flow pria-
from infancy through old age. pism in a child with sickle cell disease
• A bimodal distribution has been noted, with
peaks at 5–10 years and 20–50 years. – Low-flow priapism:
• Internationally, the overall incidence of pria- • This occurs when there is decreased
pism is 1.5 cases per 100,000 person-years. outflow from penile veins, leading to
• In men older than 40 years, the incidence venous hemostasis.
increases to 2.9 cases per 100,000 • Intracavernosal blood sampling reveals
person-years. acidosis and decreased oxygen tension.
• Cases in younger groups are more often asso- • Although the mechanism that causes
ciated with SCD, while those in older groups low-flow priapism is not fully under-
tend to be secondary to pharmacologic stood, it may be caused by the sickling of
agents. red blood cells in the sinusoids of the cor-
• The rate of priapism in adults with SCD is as pora cavernosa during normal erection.
high as 89 %. • This sickling leads to venous stasis,
• In one study, 38–42 % of adult patients with resulting in decreased local oxygen ten-
SCD reported at least one episode of sion and pH, which further potentiate
priapism. stasis, sickling, and secondary priapism.
• The rate of priapism among children with • This type of priapism is considered a
SCD is as high as 27 %. medical emergency because, if it is left
• Approximately two thirds of all pediatric untreated, irreversible cellular damage
patients who have priapism also have SCD. and fibrosis may occur, resulting in
• Priapism of the clitoris has been reported but impotence.
is extremely rare. • Low-flow priapism tends to be much
more common in patients with SCD
(Fig. 23.8).
23.9.3 Classification – High-flow priapism:
• This is thought to be secondary to
• Priapism is prolonged painful erection of the unregulated arterial inflow, leading to
penis often starting in the early hours of the prolonged but painless erection.
morning. • It is more commonly associated with
• Priapism develops when there is excess arte- penile trauma, but it has been reported
rial inflow to the penis or when there is per- in patients with SCD.
sistent venous outflow obstruction to the • Diagnosis can often be made by simple
penis. observation (erect, painless, brightly
• Two types of priapism exist based on blood colored penis) and aspiration of bright
flow patterns in the penis: red cavernosal blood.
• Since this type of priapism is associated • The corpus spongiosum on the other hand has
with the presence of a large amount of no tunica albuginea, and therefore, serves as
oxygenated blood, fibrosis and cellular an arteriovenous fistula with less rigidity than
damage do not occur, and treatment can the corpora cavernosa. The urethra runs within
occur on an elective rather than emer- the corpus spongiosum.
gent basis. • Normally, erection results from corporal
• It is important to distinguish between smooth muscle relaxation secondary to the
high- and low-flow priapism, because release of neurotransmitters.
treatment strategies differ depending on • The principal neurotransmitter for erection is
the type of priapism present. nitric oxide (NO), which is released by both
• High-flow priapism tends to require nerve terminals and endothelial cells. The NO
arterial embolization or ligation to pro- then diffuses into both trabecular cells and
duce detumescence, while low-flow arterial smooth muscle cells. This activates
priapism tends to respond to pharmaco- guanylate cyclase, which catalyzes the forma-
logic agents. tion of cGMP from GTP, and results in a cas-
• Priapism in patients with SCD is also classi- cade that decreases intracellular calcium and
fied into two types based on onset: opens potassium channels to cause smooth
– Acute severe priapism: muscle relaxation.
• This lasts longer than 4 h and can result • This result in increased blood flow and filling
in impotence. of the corpora cavernosa sinusoids with blood
– Stuttering priapism: and ultimate compression of venous outflow
• This occurs in an intermittent pattern, and trapping of blood.
lasting for a few minutes to up to 3 h • Alternative pathways generate cAMP, which
• Generally it resolve on its own enhances this effect.
• It is often recurrent and may precede a • Detumescence follows degradation of cGMP
severe attack and cAMP. cGMP is degraded by phosphodi-
• Stuttering or recurrent priapism may esterase-5 (PDE5).
occur in patients with sickle cell trait or • Typically, in priapism, the corpora cavernosa
disease. are tense, congested and tender to palpation
• Usually self-limiting in nature, over while the glans and corpus spongiosum are
time such episodes may lead to erectile usually soft and uninvolved.
dysfunction. • Stasis and low blood flow rates within the
sinusoids of the erectile tissue make the penis
a site at high risk for developing a veno-
23.9.4 Pathophysiology occlusive crisis in patients with SCD.
• SCD is genetically determined by a mutation
• Anatomically, the penis is composed of two cor- in the β-globin chain of hemoglobin.
pora cavernosa and one corpus spongiosum. • It results from a single change of one amino
• The two corpora cavernosa are made up of acid, valine for glutamic acid in the sixth posi-
smooth muscles and covered in a tunica albu- tion of the beta chain of hemoglobin.
ginea. This is made up of two layers, an inner • This results in a change in hemoglobin from
layer that supports the cavernous tissue and an hemoglobin A to hemoglobin S which is
outer layer that runs longitudinally from the known to be associated with increased mortal-
glans to insert onto the pubic rami. ity and morbidity including pulmonary hyper-
• The inner and outer layers of the tunica albu- tension, cerebral vascular accidents, lower
ginea are connected by emissary veins. extremity ulcerations, osteonecrosis, painful
crises, and priapism among other less com- • The hemolysis leads to the release of the
mon clinical problems. highly oxidative group heme and causes deg-
• Classically, in priapism, the primary mecha- radation of the cellular membrane, releasing
nism is thought to be obstruction of venous hemoglobin and arginase into the extracellular
drainage resulting in viscous, hypoxic blood environment. This is more exacerbated in
leading to interstitial edema and fibrosis of the those with functional asplenia (autosplenec-
corpora cavernosa, ultimately resulting in tomy) or surgical asplenia following
impotence. splenectomy.
• It was shown that the length of time of isch- • Free hemoglobin oxidizes into methemoglo-
emia directly correlates with the likelihood of bin, liberating heme groups and ferrous ions.
return of erectile function, and therefore, isch- • Freed arginase in the extracellular environ-
emic priapism is considered a urologic ment consumes L-arginine, a substrate for the
emergency. endothelial synthesis of nitric oxide.
• It was shown that all patients with ischemic • Nitric oxide is directly consumed in the oxida-
priapism episodes of greater than 12 h duration of hemoglobin to methemoglobin and in
tion had reduction in erectile function and no the neutralization of heme groups and ferrous
patients with priapism lasting greater than ions.
36 h had return of spontaneous erectile • The oxidative lesion, direct consumption and
function. deficit of nitric oxide synthesis cause endothe-
• Priapism in sickle cell patients has been clas- lial activation, release of inflammatory and
sically attributed to vaso-occlusion episodes. thrombogenic factors and a tendency to
• The deformed sickled red blood cells leads to vasoconstriction.
vasooclusion which is precipitated to by • Permanent vascular injuries occur over the
hypoxemia and acidosis in the corpora caver- long term, perhaps fostered by chronic tissue
nosa (caused by vasoconstriction, hypovole- hypoxemia and the synthesis of vasoprolifera-
mia or stasis in the corpora cavernosa during tive substances.
physiologic erection). • Secondary or simultaneous sinusoidal block-
• This cause microvascular obstruction, in a age by deformed red blood cells in the micro-
vicious cycle: red cells sickling causes vascu- circulation and worsening of the local process
lar obstruction and secondary ischemia, which of hemolysis may occur.
promotes new red cells sickling. • RBC hemolysis result in the release of cell-
• This however is not the case and currently, free plasma hemoglobin which scavenges
the more accepted theory is the inflammatory available NO.
theory which is based on the mediating func- • The absence of NO leads to:
tion of the vascular endothelium in the – Increased vascular tone
microcirculation. – Platelet activation
• In patients with SCA, several factors contrib- – Up regulation of vascular adhesion
ute to the development of priapism including molecules.
anatomic factors and a low-flow state. • Reduced levels of NO have been implicated
• Recently however it was shown that nitric in the pathogenesis of pulmonary hyperten-
oxide (NO) plays an important role in the sion, priapism and leg ulcers in patients with
pathogenesis of priapism in these patients. SCA.
• SCD is characterized by hemolysis, the extent • NO is an important smooth muscle relaxant
of this is variable. and a potent vasodilator. It mediates this
through increasing levels of cyclic GMP – Exposure to alcohol

(cGMP). This results in smooth muscle – The use of marijuana
relaxation, vasodilatation of penile arter- – The use of cocaine, psychotropic drugs,
ies, increased blood flow and penile erec- and testosterone
tion. This effect is regulated by • In priapism these new concepts have specific
phosphodiesterase type 5 (PDE-5) which implications, as the physiologic mechanisms
degrades cGMP. of erection are specifically controlled by nitric
• SCA patients have elevated free hemoglobin oxide.
concentrations compared to normal volunteers • Notably, priapism is more frequent in the
as a result of hemolysis. This will result in severe forms of SCD, with an association to
increase in NO scavenging with subsequent pulmonary hypertension (up to five times
prevention of vasodilation. more common than in other SCD patients) and
• Other associated risk factors for priapism strokes.
include Lactate dehydrogenase (LDH), biliru- • Episodes of priapism are also linked to a rise
bin and reticulocyte count which are elevated in serum markers of hemolysis, such as
in patients with SCA and priapism. increase of reticulocytes, indirect bilirubin,
• Chronic scavenging of NO results in a and lactate dehydrogenase (LDH).
decreased expression of downstream regula-
tory molecules including PDE5 that normally
degrades cGMP, the second messenger in NO 23.9.5 Clinical Features
signaling.
• The combination of chronically decreased • Priapism may occur at any age. The mean age
PDE5 and normal cGMP generation following of onset is 12–15 years but has been reported
nerve stimulation may result in an unregu- in children.
lated, prolonged erection. • 70–90 % of affected patients report their first
• In patients with SCA, there is: episode prior to 20 years of age.
– Reduction in NO bioavailability • The exact prevalence of priapism is not known
– A significant down regulation of PDE-5 but it has been estimated to range from 6 to
– Uncontrolled cGMP activity. 45 %.
– Elevated levels of adenosine in the penis • Priapism has been reported in various hemo-
may also contribute to the pathogenesis of globinopathies. Commonly it is seen in sickle
priapism but this has not been well cell anemia (homozygous sickle cell) but has
established. been reported in patients with hemoglobin SC
• Risk factors for priapism in SCA patients disease, sickle cell beta thalassemia and rarely
include: in those with sickle cell trait.
– Prolonged sexual activity • Priapism may occur as an isolated episode or
– Fever as part of generalized SCA vasoocclusive
– Dehydration crisis.
Red blood cells hemolysis
Free hemoglobin Arginase
No consumption
L-Arginine Polyamines
and proline
No NO synthesis
Deficient NO
Smooth muscle cell

growth
and collagen synthesis
• Endothelial cell activation
• Up-regulation of the potent
vasoconstrictor endothelin-1
• Vasoconstriction
• Platelet activation
Proliferative vasculopathy
• Increased tissue factor
• Activation of coagulation
• Priapism may occur also during sleep or fol- – Stuttering priapism typically occur in clus-
lowing an active sexual intercourse. ters, approximately two to three times per
• These patients usually present with an erect week for several weeks.
painful penis and on palpation, the penis is hard – About 60 % of those who develop stutter-
in consistency while the glans penis is soft. ing priapism will develop an attack of acute
• Many of these patients are not aware of this as priapism in the future.
a complication of SCA and this leads to delay • The majority of patients with SCD report inter-
in seeking medical advice. mittent episodes preceding an acute episode.
• The mean duration of symptoms was reported • This emphasizes the need to investigate stut-
to range from 6 to 70 h (mean 22 h). Some of tering episodes in sickle cell outpatients, in
these patients may resort to sexual intercourse order to actively prevent acute episodes and
in an attempt to relieve the pain. educate the patients.
• Stuttering priapism: • The most common precipitants of priapism are
– An episode of priapism lasting more than a sexual activity (including masturbation), dehydra-
few minutes but less than 3 h. tion, fever and exposition to a cold environment.
23.9.6 Treatment • If priapism persists beyond 4 h, intracaverno-

sal blood aspiration and instillation of an
• Priapism is a serious complication of SCD. α-agonist should be performed under local or
• There are no definitive guidelines available for regional anesthesia and repeated as needed.
the treatment of SCD-related priapism. • Alpha-agonists act as vasoconstrictors and are
• Although conservative management has com- thought to induce contraction of the smooth
monly been advocated, most experts advocate muscle of the penile arteries of the corpora
emergent surgical decompression when con- cavernosa, forcing blood out of the corpora
servative management fails. cavernosa and into the venous system.
• Patients with SCD should be educated regard- • Beta-agonists, on the other hand, act as vaso-
ing the need to seek prompt specialized treat- dilators by blocking β-receptors, resulting in
ment for any episode of priapism that lasts smooth muscle relaxation of the vasculature.
longer than 2 h. This allows oxygenated arterial blood to enter
• Numerous therapeutic options have been the cavernosa, washing out stagnant, already
attempted, including blood transfusion, damaged sickle cells.
exchange blood transfusion, diethylstilbestrol, • Various adrenergic agonists have been used in
gonadotropin-releasing hormone analogues, the treatment of priapism, including:
various adrenergic agonists, and hydroxyurea. – Pure α-agonists (e.g., metaraminol)
• Few agents have actually been examined in a – Mixed α- and β-agonists (e.g., etilefrine,
controlled clinical trial, making it difficult for phenylephrine, and epinephrine)
practitioners to treat this complication. – Pure β-agonists (e.g., terbutaline)
• The parents of children with SCD should be – Etilefrine is the ideal α-agonist to use
educated about priapism and how to treat it – Phenylephrine (preferable, since it is more
initially. selective) or epinephrine can be used also.
• Some educated and willing parents could also – Metaraminol is associated with side effects
be taught how to aspirate the cavernosa and including transient but severe hypertension.
then inject intracavernosal epinephrine or • The procedure consist of intracavernosal aspi-
phenylephrine for prolonged episodes or for ration followed by irrigation with 10 mL of a
those not relieved with oral pseudoephedrine. 1:1,000,000 solution of epinephrine.
• It is recommended that treatment should be Aspiration continued until detumescence
conservative initially. occurred. If detumescence lasts for at least
• The patient is encouraged to drink extra fluids, 30 min, the patient is discharged from the
urinate, exercise, and take oral analgesics. emergency department.
These simple measures have occasionally been • Others use intracavernosal aspiration and irri-
sufficient enough to produce detumescence. gation with diluted epinephrine (20 mL of a
• If the episode of priapism persists beyond 2 h, solution of 1 mL 1:1,000 epinephrine in 1 L of
the patient should report to the emergency 0.9 % sodium chloride) are performed.
department. – Irrigation and aspiration are performed until
– The patient is assessed clinically sustained detumescence was achieved or a
– The patient should be started on intrave- maximum of 200 mL of solution was used,
nous fluids at 1.5 their maintenance after which an emergency shunt is performed.
requirements. – If irrigation was successful, the patient is
– The patient should be given analgesics to observed for 24 h and then discharged
relive the discomfort and pain. home.
– Anxiolytics, such as lorazepam, mid- • The procedure of aspiration and irrigation
azolam, or hydroxyzine pamoate, and sup- (Figs. 23.9, 23.10, 23.11, 23.12, and 23.13):
plemental oxygen may also be given if – Apply local anesthetic blockade
needed. – A 21-gauge needle is used for children.
Figs. 23.9 and 23.10 Clinical photographs showing priapism in a child with SCA being treated with aspiration and
irrigation
– The volume of blood removed in the

aspiration:
• This should be limited to a maximum of
7.5 mL/kg (10 % of the blood volume in
children >1 year of age), because of the
risk of provoking hypovolemia or shock.
– Alpha-adrenergic agonists (etilefrine,
phenylephrine, epinephrine, metaraminol)
are then injected.
– Injection of adrenergic agents is known to
be associated with complications
including:
Fig. 23.11 Clinical photograph showing a child with • Infection
sickle cell disease and priapism being treated with aspira- • Hematomas
tion and irrigation • Urethral injury
• Fibrosis at the injection site
– Puncture one of the corpora cavernosa, • Rarely, penile necrosis.
usually via the glans – The proposed dosages are:
– In the majority of cases it is not necessary • 10 ml of adrenaline 1:1,000,000
to puncture the two corpora cavernosa. – The overall success rate is 87 %
– Blood should be collected for gas analysis – A 100 % success was reported in
and confirmation of the diagnosis. those <24 h duration of priapism
– Thereafter the corpora cavernosa are – In 20 % of cases it was necessary to
drained. repeat the injection.
– Irrigation and drainage of the full extension • Other authors propose diluting 1 mL of
of the corpora is more efficient. adrenaline 1:1,000 solution in 1 L of
saline and injecting 20 mL in repeated • Winter shunt: This creates a cavernosa-

boluses, until a maximum of ten injec- spongiosum shunt by puncturing the
tions (200 mL). glans with a Tru-Cut needle
• Etilefrine: • Al-Ghorab shunt: This suture the distal
– 5–10 mg per intracavernosal injec- extremity of the corpora cavernosa to the
tion, without dilution. spongiosum into the glans (spongiosum-
• All patients who arrive at the emer- cavernous anastomoses)
gency department within 36 h of pria- – Or a proximal shunt:
pism respond to the treatment • Grayhack shunt: laterolateral spongio-
regimen. sum to proximal penile corpora caver-
• Etilefrine can be used to treat priapism nosa suture
in patients with SCD. • A cavernosa-venous diversion to the
– 5 mg of undiluted intracavernosal etile- saphenous vein (saphenous-cavernous)
frine (if priapism was present for less shunts or to the dorsal vein of the penis.
than 6 h) or aspiration followed by irri- – The placement of a penile prosthesis should
gation with intracavernosal etilefrine be considered in adulthood, so that patients
(if priapism had been present for with erectile dysfunction as a consequence
greater than or equal to 6 h). of prior crises can become sexually active.
• If the priapism continues beyond approxi-
mately 12 h, shunt procedure should be
considered. 23.9.7 Prevention of Stuttering
• The shunt procedure should be the last option, Priapism
as it is associated with higher rates of impo-
tence, and most pediatric patients respond • Prophylaxis of recurrence of acute episodes or
well to pharmacologic treatments. of occurrence of acute episodes in patients
• To prevent relapse of priapism, patients can be with recurrent self-limited priapism include
treated with oral etilefrine 0.25 mg/kg twice a the following therapeutic proposals:
day for 1 month. – First-line treatment should begin with an
• Other less commonly used medications to oral adrenergic agonist, as they seem to
treat priapism include: have the best efficacy and safety profiles.
– Phosphodiesterase inhibitors: A single oral – Etilefrine is the best evidence-supported
dose of 50 mg is used treatment available.
– Ketamine injections (0.5–1 mg/kg) – Stuttering priapism is treated with oral
– Hydralazine etilefrine 0.5 mg/kg for 1 month. A dose is
– Calcium-channel blockers given once every evening in patients with
– Anticoagulants nocturnal priapism or divided into two
– Corticosteroids doses for priapism occurring during the
– Continuous epidural anesthesia day and at night. The treatment is continued
– Inhaled nitric oxide for 1 month after eventual resolution with
• Surgery (Figs. 23.14 and 23.15): no recurrence.
– Most authors would indicate surgery only – This can be combined with intracavernosal
in low flow priapism episodes, after 12 h, if self-injection in cases of acute episodes
conventional medical treatment and injec- lasting more than 1 h.
tion of the corpora cavernosa with adrener- – Phenylpropanolamine is an acceptable
gics could not solve the problem. alternative.
– This can be performed by a distal – Phenylephrine and epinephrine are not
cavernosa-spongiosum shunt: available in an orally active formulation.
Figs. 23.12 and 23.13 Clinical photographs showing priapism in a child with SCA being treated with aspiration and
irrigation. Note the response to the treatment with resolution of priapism
– The third step that should be considered is

the use of a gonadotropin-releasing hor-
mone analogue plus flutamide.
• Leuprolide is the agent of choice.
• Flutamide should be given initially to
minimize the testosterone flare often
seen upon initiation of gonadotropin-
releasing hormone analogues.
– Hormonal manipulation is also used in the
treatment of recurrent priapism.
– Gonadotropin-releasing hormone ana-
logues have fewer risks and adverse effects
than those seen with diethylstilbestrol.
– Overall, gonadotropin-releasing hormone
Figs. 23.14 and 23.15 Clinical photograph showing analogues appear to be relatively safe and
priapism in an adult with SCA being treated with a distal well tolerated by most patients.
glans-cavernosal shunt – Gonadotropin-releasing hormone ana-
logues also offer the convenience of
– Pseudoephedrine is the only preferred oral monthly or quarterly administration rather
adrenergic agonist available. It may be than the daily or weekly administration
given as a once-daily dose at bedtime or as needed with oral medications.
two doses given in the morning and at – Use of anti-androgenic hormonal manipu-
bedtime lation, using gonadotrophin inhibitors
– Terbutaline is an alternative, but it should (goserelin, leuprolide) or finasteride to
be considered a second-line therapy behind reduce androgen levels.
pseudoephedrine, as there is less evidence – This treatment, although efficacious, is
supporting its efficacy. associated with side effects (loss of libido
– Other oral agents that may be tried if pseu- and erectile function). Those drugs are sec-
doephedrine fails include hydralazine, ond- or third-line treatment options.
pentoxifylline, and diltiazem, although evi- – Adverse effects have been reported in over
dence for the use of these three drugs is 2 % of pediatric patients using leuprolide
weak, and their routine use cannot be fully and include injection-site reactions, gener-
advocated. alized pain, rash, and acne. The concern
with using them in pediatric patients is that endothelium resulting in blood “trap-
sexual maturation may be delayed second- ping” and, thus, priapism.
ary to the reduction of circulating andro- • It is often used to treat patients with
gens, which can cause the reproductive SCD who have recurrent pain crises.
organs to return to a prepubertal state. • Hydroxyurea maybe useful in the treat-
– Other agents which may be considered are ment of sickle-cell-induced priapism.
diethylstilbestrol and hydroxyurea. • Given the side effects and risks, this
• Diethylstilbestrol is effective but has approach has been reserved for serious
side effects. cases.
• Hydroxyurea should decrease the • Its adverse effects preclude its use as a
degree of sickling, which is thought to first-line drug to treat priapism.
be the major cause of priapism in • Major adverse effects of hydroxyurea
patients with SCD. However, its adverse include myelosuppression (leukopenia,
effects also limit its use. anemia, and occasionally thrombocyto-
– Diethylstilbestrol: penia), elevation of hepatic enzymes,
• This is used to abort and prevent stutter- gastrointestinal symptoms (nausea, vom-
ing priapism. iting, diarrhea, constipation, stomatitis,
• The exact mechanism by which diethyl- anorexia), renal impairment, fever, chills,
stilbestrol works is unknown. malaise, edema, erythema, and rash.
• Its use is limited by the recurrence of – There have been case reports describing the
symptoms 6–8 weeks after discontinua- isolated but successful use of other phar-
tion of the medication and because of macologic agents to induce detumescence
the side effects (loss of libido and erec- in patients with prolonged erection such as
tile function, gynecomastia, testicular ketamine and hydralazine.
atrophy). – Methylene blue injected intracavenously
• It should be considered a last resort has also been reported to be effective in the
medication, not appropriate for use in treatment of priapism. Methylene blue can
pre-pubescent patients. however cause necrotic abscess.
• Diethylstilbestrol 5 mg daily for – The use of erythrocyte transfusions for
3–4 days could abort attacks of pria- 6 months, followed by pentoxifylline for
pism, and individualized dosages lower 6 months.
than 5 mg daily could be used to prevent • Blood transfusion:
priapism. – Both simple and exchange transfusions
• Other adverse effects commonly experi- have been used in attempts to increase the
enced with diethylstilbestrol include hemoglobin and hematocrit, decrease the
breast tenderness and enlargement, nau- number of sickled red blood cells, decrease
sea, vomiting, abdominal cramps, head- hemoglobin S levels, and increase the num-
ache, dizziness, weight changes, edema, ber of oxygenated, normal erythrocytes.
changes in libido, hirsutism, and testicu- – Exchange transfusions have been ques-
lar atrophy. tioned for three main reasons:
– Hydroxyurea: • Absence of good quality scientific evi-
• It induces the synthesis of fetal hemo- dence of its efficacy.
globin, modifying the mechanisms of • The well-known risks associated with
endothelial activation and resulting in transfusion.
general improvement of SCD. • Availability of blood and difficulties in
• It may also reduce neutrophil and retic- obtaining blood for emergency exchange
ulocyte counts, thereby decreasing the and noncompliance of parents when it is
interaction of sickle cells with vascular used to prevent recurrent attacks.
– However, transfusions for priapism have 36 h after the onset of priapism develop erec-
been associated with ASPEN syndrome, a tile dysfunction.
syndrome characterized by the association • If irreversible damage has been done, long-
of SCD, priapism, exchange transfusion, term management of erectile dysfunction may
and neurologic events. The most serious be treated with placement of a penile prosthe-
event associated with this syndrome is sis to restore function depending on the pref-
cerebrovascular accident. erence of the patient.
– Exchange blood transfusion: • A severe and prolonged episode of priapism
• This is done using packed RBCs. will result in cavernous smooth muscle necro-
• This however may be associated with sis, fibrosis, and ultimately penile shortening.
neurological complications including • If erectile function is unlikely to recover,
headaches, seizures and obtundation. immediate implantation of a penile prosthesis
• These complications may be related to may, therefore, be considered to avoid the
the rapid elevation of Hb to above 12 g/ complications of penile fibrosis and shorten-
dl and release of procoagulant and vaso- ing of the penis.
active factors from the corpora • The prognosis for erectile function in sickle
cavernosa. cell patients is poor.
• To ovoid this, the target of exchange • Most authors report that one fourth to one half
RBCs transfusion should be a Hb <10 g/ of patients become impotent after prolonged
dl and hemoglobin S <50 %. episodes of priapism.
• A regular simple packed RBCs transfu- • The prognosis may be better for prepubertal
sion was found beneficial for those with children.
stuttering or repeated attacks of pria- • Acute cases have a much poorer prognosis
pism. The aim is to reduce HbS level to than cases of intermittent priapism.
less than 30 %.
– Other therapies reported in the literature
include calcium-channel blockers, such as Further Reading
verapamil, diltiazem, and nifedipine; hyal-
uronidase; and anticoagulants. 1. Adeyoju AB, Olujohungbe ABK, Olujohungbe
ABK. Priapism in sickle-cell disease; incidence, risk
factors and complications—an international multi-
center study. Br J Urol Int. 2002;90(9):898–902.
23.9.8 Complications of Priapism 2. Burnett AL, Bivalacqua TJ, Champion HC, Musicki B.
and Prognosis Long-term oral phosphodiesterase 5 inhibitor therapy
alleviates recurrent priapism. Urology. 2006;67:1043–8.
3. Chacrabarty A, Upadhyay J, Dhabuwala CB, Sarnaik
• Most episodes of priapism resolve without S, Perlmutter AD, Connor JP. Priapism associated
complications. with sickle cell hemoglobinopathy in children: long-
• These are usually of short duration. term effects on potency. J Urol. 1996;155:1419.
4. El-Banasawy MS, Dawood A, Farouk A. Low flow
• Prolonged episodes of priapism on the other
priapism: risk factors for erectile dysfunction. BJU
hand may lead to fibrotic changes in the cor- Int. 2002;89:285–90.
pora cavernosa and subsequently erectile 5. Gbadoe AD, Atakouma Y, Kusiaku K, Assimadi
dysfunction. JK. Management of sickle cell priapism with etile-
frine. Arch Dis Child. 2001;85:52–3.
• These changes are time dependent and after
6. Kato GJ, McGowan V, McGowan V. Lactate dehydro-
24–48 h of priapism irreversible changes genase as a biomarker of hemolysis-associated nitric
develop leading to erectile dysfunction. oxide resistance, priapism, leg ulceration, pulmonary
• It has been reported that SCA patients who hypertension, and death in patients with sickle cell
disease. Blood. 2006;107(6):2279–85.
present with priapism and seek medical advice
7. Liu J, Al-Hothari MA, Mahboob FA. Non-surgical
within 12 h usually retain normal erectile treatment of recurrent or stuttering priapism in sickle
function while all those who present beyond cell children. Saudi Med J. 2003;24:1143–5.
Further Reading 525
8. Mantadakis E, Ewalt DH, Cavender JD, Rogers ZR, 13. Salem EA, ElAasser. Management of ischemic pria-
Buchanam GR. Outpatient penile aspiration and epi- pism by penile prosthesis insertion: prevention of dis-
nephrine irrigation for young patients with sickle cell tal erosion. J Urol. 2010;183:2300–3.
anemia and prolonged priapism. Blood. 2000;95:78–82. 14. Siegel JF, Rich MA, Brock WA. Association of sickle
9. Maples BI, Hagemann TM. Treatment of priapism in cell disease, priapism, exchange transfusion and neu-
pediatric patients with sickle cell disease. Am J Health rological events: ASPEN syndrome. J Urol. 1993;150:
Syst Pharm. 2004;61:355–63. 1480–2.
10. Miller ST, Rao SP, Dunn EK, Glassberg KI. Priapism in 15. Van der Horst C, Stuebinger H, Seif C, Melchior D,
children with sickle cell disease. J Urol. 1995;154:844–7. Martinez-Portillo FJ, Juenemann KP. Priapism: etiol-
11. Rogers ZR. Priapism in sickle cell disease. Hematol ogy, pathophysiology and management. Int Braz
Oncol Clin N Am. 2005;19:917. J Urol. 2003;29:391–400.
12. Saad ST, Lajolo C, Gilli S, Marques Junior JF, Lima 16. Wen C, Munarriz R, Mcauley I, Goldstein I, Traish A,
CS, Costa FF, et al. Follow-up of sickle cell disease Kim N. Management of ischemic priapism with high-
patients with priapism treated by hydroxyurea. Am dose intracavernosal phenylephrine: from bench to
J Hematol. 2004;77:45–9. bedside. J Sex Med. 2006;3(5):918–22.
Undescended Testes
(Cryptorchidism) 24
24.1 Introduction For unilateral cases the left testicle is more

commonly affected
• Cryptorchidism is derived from the Greek • In 80–90 % of cases, an undescended testis
kρυπτός, kryptos, meaning hidden and ὄρχις, can be felt in the inguinal canal; in a minority
orchis, meaning testicle. the testis or testes are in the abdomen or non-
• It is defined as the absence of one or both tes- existent (truly “hidden”).
tes from the scrotum (Fig. 24.1). • It has been estimated that the incidence of
• Undescended testis was first described in 1786 undescended testis in premature male new-
by Hunter and has been recognized for borns is about 30 %.
centuries. • The incidence of undescended testes in full-
• The first surgical orchiopexy was attempted in term male newborns is 3–5 %.
1820 by Rosenmerkal. • This incidence decreases to 0.8 % at 3 months
• Annandale in 1877 performed the first suc- of age as some of these undescended testes
cessful orchiopexy. will descend to the scrotum spontaneously.
• In 1899, Bevan published the principles of tes- • In the United States, the prevalence of crypt-
ticular mobilization, separation of the proces- orchidism ranges from 3.7 % at birth to 1.1 %
sus vaginalis, and repositioning of the testis from age 1 year to adulthood.
into the scrotum.
• It is considered the most common birth defect
of the male genitalia.
– It is estimated that about 3 % of full-term
and 30 % of premature infant boys are born
with at least one undescended testis.
– It is also estimated that about 80 % of unde-
scended testes descend by the first year of
life and the majority of them descend
within the first 3 months of life.
– This makes the true overall incidence of
undescended testes around 1 %.
• About 75–80 % of undescended testes are
unilateral.
• Cryptorchidism can affect one or both testes Fig. 24.1 A clinical photograph showing undescended
and approximately 10 % of cases are bilateral. right testis

528 24 Undescended Testes (Cryptorchidism)

photograph showing
bilateral intraabdominal
testes in a patient with
testicular feminization
syndrome
Fig. 24.3
Intraoperative
photograph showing a
hernia sac containing
intraabdominal testis in
a patient with testicular
feminization syndrome
• Internationally, the prevalence of cryptorchi- – Twinning

dism ranges from: – Maternal exposure to estrogen during the
– 4.3–4.9 % at birth first trimester
– 1–1.5 % at age 3 months • Sometimes undescended testes are found inci-
– 0.8–2.5 % at age 9 months dentally during routine herniotomy in patients
• Siblings of boys with undescended testes are with testicular feminization syndrome
at increased risk for cryptorchidism, with a (Figs. 24.2 and 24.3).
reported incidence of up to 10 %. • Early diagnosis and management of the unde-
• Cryptorchidism is identified in 1.5–4 % of scended testicle are important to preserve fer-
fathers and 6.2 % of brothers of patients with tility and improve early detection of testicular
cryptorchidism. malignancy.
• Heritability in first-degree male relatives is • The recent improvements in surgical tech-
estimated to be 0.67. nique, including laparoscopic diagnosis and
• True undescended testicles rarely descend into the treatment of undescended testes are likely to
scrotum spontaneously after 4 months of age. improve outcomes.
• Factors that Predispose to cryptorchidism • According to the guidelines published by the
include: American Urological Association in May 2014:
– Prematurity – Imaging for cryptorchidism is not recom-
– Low birth weight mended prior to referral, which should
– Small size for gestational age occur by 6 months of age.
– Orchiopexy is the most successful • Orchidopexy does not reduce the risk of tes-
therapy to relocate the testis into the ticular cancer, but it makes it easier to diagnose
scrotum. it early through testicular self-examination.
– Hormonal therapy is not recommended. • About 20 % of testicular tumors in men with
– Successful scrotal repositioning of the tes- unilateral cryptorchidism occur on the side
tis may reduce but does not prevent the with the normally descended testicle.
potential long-term issues of infertility and • Undescended testes have also an increased
testis cancer risk of testicular torsion. Torsion of an intra-
– Appropriate counseling and follow-up of abdominal testis may present as an acute
the patient are essential abdomen.
• Undescended testes are known to be associ- • Undescended testes are also known to be asso-
ated with complications which include: ciated with an inguinal hernia (Patent proces-
– Reduced fertility sus vaginalis) which is repaired at the time of
– Increased risk of testicular germ cell orchidopexy. If an overt hernia is present in
tumors association with undescended testis, hernia
– Undescended testes are known to be associ- repair with orchidopexy should be done at the
ated with inguinal hernia which can be com- time of diagnosis. This is to avoid the risk of
plicated by irreducibility and strangulation irreducibility and strangulation.
– Psychological problems when the boy • The classification of undescended is based on
grows up the physical and operative findings of unde-
– Undescended testes are also more suscep- scended testes:
tible to testicular torsion and subsequent – True undescended testicles: This can be
infarction • Intra-abdominal (nonpalpable)
– Undescended testes are more prone to • Peeping testis at the internal ring
trauma • Canalicular or inguinal testes
• It has been shown that men who have had an • Undescended testes at the upper
undescended testis have: scrotum
– Lower sperm counts – Ectopic testicles
– Poorer quality of sperms – Retractile testicles
– Lower fertility rates than normal men • About one half of nonpalpable testes are found
• The likelihood of subfertility increases in to be intra-abdominal, while the rest represent
those with bilateral undescended testes and absent (vanishing) or atrophic testes.
increasing age at the time of orchidopexy. • The vanishing testicle is thought to be caused
• The risk of subfertility can be reduced by by intrauterine testicular torsion.
early orchidopexy. • Sometimes tissue in the scrotum may be pal-
• This is one reason why orchidopexy should be pable and it feels like an atrophic testis. This
done early as early as 6 months of age and not should not be taken for granted and sometimes
later than 2 years of age. this tissue represents the gubernaculum or a
• An increased incidence of epididymal abnor- dissociated epididymis and vas deferens, and
malities in undescended testes also contrib- may coexist with an intra-abdominal testis.
utes to infertility. • The presence of bilateral nonpalpable testes in
• It has been well documented that men with a a phenotypically male newborn should be
history of undescended testicle have a higher- taken seriously. The possibility of a genetic
than-expected incidence of testicular germ female with congenital adrenal hyperplasia
cell cancers. The incidence of testicular can- and in an older child testicular absence must
cer among men with an undescended testis is be kept in mind. These patients should be
approximately 1 in 1,000 to 1 in 2,500. This is evaluated including:
significantly higher than the risk among the – Pelvic ultrasound
general population (1:100,000). – Karyotyping
– Measurements of serum electrolytes, Sertoli cells. The germ cells become fetal
testosterone, luteinizing hormone (LH), spermatogonia.
follicle-stimulating hormone (FSH), – The developed testes have two types of
müllerian-inhibiting hormone (MIH), and cells:
adrenal hormones and metabolites • The Leydig cells
(17-hydroxyprogesterone). • The Sertoli cells
– A stimulation test using intramuscular – The Sertoli cells produce the anti-Müllerian
human chorionic gonadotropin (hCG) can hormone (AMH).
be done to check for evidence of testoster- – The Leydig cells produce testosterone.
one production by the gonads. – The AMH acts on its receptor in the
– Pelvic ultrasound is useful in infants with Müllerian ducts and causes their regression.
bilateral nonpalpable testes not only to – Testosterone acts in a critical concentration-
look for gonads but also to exclude the dependent and time-dependent manner to
presence of a uterus. induce male sexual differentiation.
– Ultrasonography, computed tomography or – Testosterone acts on the androgen receptor
magnetic resonance imaging, are not sensi- in the Wolffian ducts to induce the forma-
tive or specific enough to detect the major- tion of:
ity of intra-abdominal testes and surgical • Epididymis
exploration or laparoscopy is required. • Ejaculatory ducts
• Seminal vesicles.
– The Leydig cells also produce insulin-like
24.2 Embryology and Normal factor 3 (INSL3, relaxin-like factor), which
Testicular Development play a role in the descent of testes to the
and Descent scrotum.
– Testosterone is also converted to dihy-
• Embryologically, the testes develop in the drotestosterone (DHT) under the influence
abdomen along the gonadal ridge from the of 5-alpha reductase enzyme, which acts
primitive (indifferent) gonad. This is under the on the androgen receptor of the prostate
influence of several male genes. and external genitalia to cause its
• This occurs at about the sixth week of gesta- masculinization.
tion under the influence of the SRY gene. – Binding of Testosterone and DHT to andro-
– The SRY gene is located on the short arm gen receptors is necessary for androgen
of the Y-chromosome (Yp11.3). It is effect.
responsible for initiating sex differentiation • The testes remain high in the abdomen until
by downstream regulation of sex- the seventh month of gestation, when they
determining factors. start descending from the abdomen through
– This involves expression of several genes the inguinal canals into their final position in
including WT1, CBX2 (M33), SF1, GATA4/ the scrotum.
FOG2 is critical to SRY activation. • It has been proposed that testicular descent
– The SOX9 gene, located on 7q24.3-25.1, is from the abdomen into the scrotum occurs in
essential for early testis development. two phases, under control of somewhat differ-
• The second step in male sex differentiation ent factors.
involves internal and external genitalia – The first phase:
differentiation. • This involves descent of the testes from
• During the third to fifth months of intra- the abdomen to the entrance of the
uterine development, the cells in the testes dif- inguinal canal.
ferentiate into testosterone-producing Leydig • This phase is under the influence of the
cells, and anti-Müllerian hormone-producing anti-Müllerian hormone (AMH).
24.4 Causes of Undescended Testes and Risk Factors 531
– The second phase: abdomen, just below the kidney, to the upper part
• This involves descent of the testes of the scrotum.
through the inguinal canal into the – In the abdomen: These are not palpable
scrotum. – In the inguinal canal
• This phase under the influence of andro- – Just above the scrotum
gens (testosterone). • Retractile testis: A testis that can easily move
• It was shown experimentally that andro- between the scrotum and inguinal canal.
gens induce the genitofemoral nerve to • Ectopic testis: A testis that descended but have
release calcitonin gene-related peptide “wandered” from the normal path of descent
(CGRP), which causes rhythmic contrac- to lie outside the inguinal canal.
tions of the gubernaculum that help facili- – In the superficial inguinal pouch
tates testicular descend into the scrotum. – Under the skin of the thigh
• It was also suggested that the testes – In the perineum
secret a hormone called descendin – Prepenile are
which through a paracrine effect help in – In the opposite scrotum
testicular descent. – In the femoral canal
• In many infants with inguinal testes, • Undeveloped (hypoplastic) testis
further descent of the testes into the • Severely abnormal (dysgenetic) testis
scrotum occurs in the first 6 months of • Vanished testis: This is most likely secondary
life. This is attributed to the postnatal to intrauterine torsion of testes with infarction
surge of gonadotropins and testosterone and necrosis
that normally occurs between the first • Ascent testis: A testis observed in the scrotum
and fourth months of life. in early infancy can occasionally “reascend”
• Factors that can affect testicular descent (move back up) into the inguinal canal.
include: • Most normal-appearing undescended testis
– Maldevelopment of the gubernaculum are also normal by microscopic examination,
– Deficiency or insensitivity to AMH but reduced spermatogonia can be found. The
– Deficiency or insensitivity to androgen tissue in undescended testes becomes more
– Anatomical factors that interfere with tes- markedly abnormal (“degenerates”) in micro-
ticular descent scopic appearance between 2 and 4 years after
• Spermatogenesis continues after birth. birth. There is some evidence that early orchi-
– In the third to fifth months of life, some of dopexy reduces this degeneration.
the fetal spermatogonia residing along the
basement membrane become type A
spermatogonia. 24.4 Causes of Undescended
– More gradually, other fetal spermatogonia Testes and Risk Factors
become type B spermatogonia and primary
spermatocytes by the fifth year after birth. • In the majority of undescended testes, no defi-
– Spermatogenesis arrests at this stage until nite cause can be found
puberty. • Several factors may contribute to the develop-
ment of cryptorchidism including genetics,
maternal health and other environmental fac-
24.3 Classification tors. These include:
of Undescended Testes – Parents’ exposure to some pesticides
– Diabetes and obesity in the mother
• A testis absent from the normal scrotal position – Exposure to regular alcohol consumption
can be found any were along the “path of descent” during pregnancy
from high in the posterior (retroperitoneal) – Cigarette smoking
Figs. 24.4 and 24.5 Clinical photographs showing two patients with severe hypospadias and bilateral undescended
testes
– Family history of undescended testicle • Cryptorchidism occurs at a much higher rate

– The use of cosmetics by the mother in a large number of congenital malformation
– Preeclampsia syndromes including:
– Prenatal exposure to a chemical called – Down syndrome
phthalate (DEHP) which is used in the – Prader–Willi syndrome
manufacture of plastics – Noonan syndrome
– Exposure to mild analgesics by pregnant – Kallmann’s syndrome
mothers – Laurence-Moon-Biedl syndrome
• Premature infants and low birth weight infants – Sever penoscrotal or perineal hypospadias
are known to have a higher incidence of unde- (Figs. 24.4 and 24.5)
scended testes. – Prune belly syndrome (Fig. 24.6)
• Intra-abdominal pressure also appears to play – Spigelian hernia (Figs. 24.7, 24.8, 24.9,
a role in testicular descent. and 24.10)
– Conditions associated with decreased pres- – Omphaloceles (Figs. 24.11 and 24.12)
sure include: – Gastroschesis and Cloacal exstrophy
• Prune belly syndrome (Figs. 24.13 and 24.14)
• Cloacal exstrophy
• Omphalocele
• Gastroschisis 24.5 Histopathology
– Each is associated with an increased risk of
undescended testes. • There are several histopathological changes in
• The effect of decreased intra-abdominal pres- undescended testes.
sure is most significant during transinguinal • A significant decrease in the number of sper-
migration to the scrotum, probably in matogonia per tubule (S:T ratio) in undescended
conjunction with androgens and a patent pro- testes is seen as early as the second year of life.
cessus vaginalis. • Undescended testes also have atrophic Leydig
• Epididymal abnormalities often accompany cells, supporting the observation that testos-
undescended testes, but the causal relationship terone secretion is impaired in cryptorchidism
has not been established. during early infancy.
24.6 Classification of Abnormal Testes 533

photograph showing a
patient with prune belly
syndrome and
undescended testes
• Patients with poor testicular histology (S:T ratio • A testis that is absent from the normal intra-
less or equal to 0.1) and at high risk for impair- scrotal position can be:
ment of fertility may benefit from treatment – True undescended testis: The testis can be
with Buserelin, a luteinizing, hormone-releasing found anywhere along the “path of testicu-
hormone (LHRH) analogue. lar descent”.
• There was a significant increase in mean S:T • High in the posterior (retroperitoneal)
ratio in testes rebiopsied after orchiopexy and abdomen
6 months treatment with Buserelin, while • Below the kidney
there was no change seen following orchio- • At the inguinal ring
pexy alone. • In the inguinal canal
• Although the retractile testicle is considered a • At the upper scrotum
normal variant, some studies suggest that not – Ectopic testis: This is a testis that “wan-
all retractile testes have a benign course. dered” from the normal path of descent.
– Some ascend into the undescended posi- Ectopic testes exit the external inguinal
tion and these require orchidopexy ring and are then misdirected away from
– Others show volume loss and histological the normal course of descent. This can be
abnormalities that are similar but less severe found:
than those found in cryptorchid testes. • Outside the inguinal canal
– There are also reports of infertile adults • Under the skin of the thigh
with persistent retractile testicles who have • The perineum
improved sperm counts after scrotal • The opposite scrotum
orchiopexy. • The femoral canal
• Prepenile
– Hypoplastic testis
24.6 Classification of Abnormal – Dysgenetic testis
Testes – Vanished (anorchia) testis
• The vanishing testicle is thought to
• Normally both testes are present in their nor- be caused by intrauterine testicular
mal intra-scrotal position at the time of birth. torsion.
Figs. 24.7, 24.8, 24.9, and 24.10 Clinical and intraoperative photographs showing Spegelian hernia and undescended
testis
• This is most likely during late gestation lated into the scrotum and there is a high
since most of these testicular remnants are risk of ascent.
found below the internal inguinal ring. • About 70–80 % of undescended testis are
• Only 20–40 % of nonpalpable testes are unilateral.
absent upon surgical exploration. • 10–20 % of undescended testes are bilateral.
– Ascent testis: A testis that descended nor- • Approximately 80 % of undescended testes
mally in the scrotum can occasionally are palpable and 20 % are nonpalpable.
“reascend” back up into the inguinal • In 90 % of undescended testes, the testis can
canal. be felt in the inguinal canal.
– Retractile testis: A testis which can move • About one half of nonpalpable testes are found
up and down between the scrotum and to be intra-abdominal, while the rest represent
inguinal canal. These testes can be manipu- absent (vanishing) or atrophic testes.
24.6 Classification of Abnormal Testes 535
Figs. 24.11 and 24.12 Clinical photographs showing omphaloceles and associated bilateral undescended testes
Figs. 24.13 and 24.14 Clinical photographs of gastroschesis and cloacal exstrophy which are known to be associated
with undescended testis
• A patent processus vaginalis is found in • 30–80 % of undescended testes are associated

more than 90 % of patients with undescended with some type of epididymal abnormality
testis (Figs. 24.15, 24.16, 24.17, and 24.18).
UNDESCENDED TESTIS
PALPABLE (80%)
NONPALPABLE (20%)
INTRA-ABDOMINAL ABSENT
TRUE ECTOPIC RETRACTILE

UNDESCENDED
Fig. 24.15 Intraoperative photograph in child with

undescended testis. Note the vas looping before it
Fig. 24.16 Intraoperative photograph showing unde-
joined the testis. Note also the abnormal epididymis
scended testis. Note the abnormal epididymis

photograph showing
bilateral undescended
testes which are small in
size. Note also the
abnormal epididymis
24.7 Clinical Features and Diagnosis 537
• Only 20–40 % of nonpalpable testes are absent

upon surgical exploration.
• Ectopic testes exit the external inguinal ring
and are then misdirected along the normal
course of the testis.
• Ectopic testes can be found in the:
– Superficial inguinal pouch
– Femoral triangle
– Prepenile are
– Perineal area
Fig. 24.18 A clinical intraoperative photograph showing – Contralateral hemiscrotum
a small atrophic testis • Retractile testes:
– These may be palpated anywhere along the
natural course of the testis, although most
24.7 Clinical Features of them are inguinal.
and Diagnosis – Although not truly undescended, these tes-
tes may be suprascrotal secondary to an
• The patient should be warm and relaxed for active cremasteric reflex. This reflex is usu-
proper examination. ally weak in infants and most active in boys
• The patient can be placed in the frog-leg posi- aged 5 years.
tion for examination. This is especially useful – These testes can be manipulated into the
in obese children and makes it easier to pal- scrotum, where they remain without tension.
pate the testis. – This condition is considered a variant of
• The diagnosis of undescended testes is normal; however, the risk of ascent may
clinical. approach 50 %.
• The scrotum is hypoplastic and in those with – Ascent probably represents an undescended
palpable undescended testes, the testes can be testis that was almost in normal position.
felt in the inguinal canal or upper part of the The distinction can be difficult, even to an
scrotum. experienced pediatric urologist. Therefore,
• In cryptorchidism, the most important factor children with retractile testes should be
is whether the testes are palpable or not. monitored regularly, at least until puberty.
• Approximately 80 % of undescended testes • The clinical anatomic position of cryptorchid
are palpable and 20 % are nonpalpable. testes are as follows:
• Nonpalpable testes may be: – Nonpalpable (33 %)
– Intra-abdominal – Palpable above the pubic tubercle (12 %)
– Absent – Palpable at the pubic tubercle (35 %)
• Palpable testes may be: – Palpable in the upper scrotum (15 %)
– Undescended – Ectopic testes (5 %)
– Ectopic • The anatomic position of cryptorchid testes at
– Retractile the time of surgery are as follows:
• Most intra-abdominal testes are found within – Intra-abdominal testis (9 %)
a few centimeters of the internal ring. – Peeping testis (20 %)
• Absent or vanishing testes are thought to be – Palpable at the pubic tubercle (42 %)
due to an intrauterine or perinatal vascular – Palpable at upper scrotum (8 %)
event, most likely during late gestation since – Superficial inguinal pouch (SIP)/
most of these testicular nubbins are found ectopic – 12 %
below the internal inguinal ring. – Absent or atrophic – 9 %
• Associated anomalies: • Moreover, approximately 23–86 % of

– Patent processus vaginalis maldescended testes have been associ-
– Abnormal epididymis: Epididymal abnor- ated with some form of epididymal
malities are seen in 32–79 % of children abnormality. The severity of these epi-
with undescended testis didymal abnormalities is more in those
– Cerebral palsy with intra-abdominal testis.
– Mental retardation – Males with undescended testis are 40 times
– Wilms tumor as likely to develop testicular cancer as
– Abdominal wall defects (e.g. gastroschisis, males without undescended testis.
omphalocele, prune belly syndrome) – Ten percent of testicular cancer cases
– Hypospadias involve patients with undescended testis.
• It is important to distinguish between a true • Recent studies have shown that prepu-
undescended testis and a retractile one. In bertal orchiopexy reduces this risk.
retractile testes, the scrotum is usually devel- • Clearly, the ability for patients to per-
oped and the testes can be brought down to the form testicular self-examination with
bottom of the scrotum. Sometimes, the scro- the testes in the scrotum is a benefit of
tum is not well developed in those with retrac- surgery.
tile testes that are outside the scrotum most of • The location of the undescended testis
the time. affects the relative risk of testicular can-
• Retractile testes are more common than truly cer. Up to 50 % of malignant testicular
undescended testes and do not need to be tumors associated with cryptorchidism
operated on. involve intra-abdominal testes.
• In those with non-palpable testes, pelvic ultra- • Seminoma is the most common malig-
sound or magnetic resonance imaging is per- nant tumor type associated with
formed to locate the testes. cryptorchidism.
• The presence of a uterus by pelvic ultrasound – Correction of associated hernia: A patent
suggests either persistent Müllerian duct syn- processus vaginalis is found in more than
drome (AMH deficiency or insensitivity) or a 90 % of patients with undescended testis.
severely virilized genetic female with congen- – Prevention of testicular torsion
ital adrenal hyperplasia. – Prevention of traumatic injury to the testis
• A karyotype can confirm or exclude forms of against pubic bone
dysgenetic primary hypogonadism, such as – Preventing of psychological effects of an
Klinefelter syndrome or mixed gonadal empty scrotum
dysgenesis. • The timing of orchidopexy is still not well
• Hormone levels (especially gonadotropins established.
and AMH) can help confirm that there are hor- • It was shown that an undescended testes is
monally functional testes. likely to descend within the first 4–6 months,
• An unambiguous micropenis, especially so an undescended testes that does not descend
accompanied by hypoglycemia or jaundice, by this time is unlikely to descend and needs
suggests congenital hypopituitarism. to be operated on.
• The treatment of undescended testes can be:
– Hormonal
24.8 Treatment – Surgical
– A combination of the two
• Benefits of orchidopexy: • Hormonal treatment:
– Increase the likelihood of fertility – This is based on the fact that testicular
• Infertility is associated with cryptorchi- descent is hormonally mediated and so
dism, and the risk of infertility increases it can be induced with hormone
with the degree of maldescent. administration.
24.8 Treatment 539
– The use of hormonal therapy however is – Side effects of hCG include:

still controversial. • Increased penile size
– There are those who advocate using hor- • Growth of pubic hair
monal therapy even for palpable unde- • Increase in scrotal rugae
scended testes. Hormonal therapy is • Pigmentation
sometimes attempted and occasionally • Erection
successful. • Increased testicular size
– Hormonal therapy has been employed in • Hyperactivity and aggressive behavior
Europe for many years as a primary ther- • Surgical treatment:
apy for cryptorchidism; the main hormones – The treatment of undescended testes is sur-
used are human chorionic gonadotropin gical orchidopexy.
(hCG) and luteinizing hormone (LH)- – At present, surgical orchidopexy is to be
releasing hormone (LHRH). done at approximately 1 year of age.
– The most commonly used hormone ther- – This recommendation is based on several
apy is human chorionic gonadotropin factors:
(HCG). • Spontaneous testicular descent is
– hCG, which is administered intramuscu- unlikely after this age
larly is the main hormonal treatment for • Histological abnormalities are subse-
undescended testes. quently more likely
– There are many protocols for the use of • Orchidopexy also allows early detection
hCG. of any testicular cancer, reduced risk of
• One such protocol is the administration trauma and torsion, and improvement in
of 1,500–2,500 U two times per week germ cell function and ultimate progno-
for 4 weeks. sis of fertility
• Others use smaller dosage depending on • Treatment of associated hernia when
the age of the patient. present
– <1 year old: 500 units are given • Surgical orchidopexy avoids several
two times per week for five to ten hormonal injections and their side
doses. effects.
– 1–2 year old: 1,000 units are given – In those with palpable undescended testes,
two times per week for five to ten open orchiopexy (inguinal orchidopexy) is
doses. the treatment of choice.
– >2 year old: 1,500 units are given – Others use a scrotal approach to mobilize
two times per week for five to ten and fix palpable undescended testes.
doses. – This is often performed as an outpatient
– The reported success rates of hCG hor- procedure.
monal therapy is variable ranging from 5 % – Several surgical approaches to the unde-
to as high as 50 %. scended testis have been described.
– Others use GnRH analogs such as nafarelin – The approach chosen is determined by the
or buserelin. position of the testis and the surgeon's
– Gonadotropin-releasing hormone (GnRH) expertise.
is suggested to be more effective than hCG – The palpable testis can be approached via
in achieving testicular descent. This how- one of the following approaches:
ever is not widely used because of conflict- • A scrotal
ing results. • A subinguinal
– Many surgeons do not consider the success • An inguinal (Fig. 24.19)
rates of hormonal therapy high enough to • A suprainguinal approach
be worth the trouble since the surgery itself – Sometimes exploration may reveal a small
is usually simple and uncomplicated. atrophic testis with a vas and vessels. This
suggests an intrauterine torsion. The con- – Diagnostic laparoscopy is the most reliable
tralateral testis needs to be fixed to prevent technique for localizing the nonpalpable
subsequent torsion (Fig. 24.20). testis.
– Rarely, exploration for an undescended tes- – It is performed in conjunction with defini-
tis may reveal features of persistent tive therapy (laparoscopic orchiopexy or
Mullerian duct syndrome (Fig. 24.21). open orchiopexy).
– The nonpalpable testis can be approached – Laparoscopic findings can be helpful in
via one of the following approaches: determining the need for inguinal explora-
• An inguinal tion, for deciding between one-stage and
• A suprainguinal two-stage repair, and for assessing gonadal
• A laparoscopic viability.
– In patients with intraabdominal unde- – Blind-ending vas and vessels confirm the
scended testis, laparoscopic assisted orchi- diagnosis of a vanishing testis and do not
dopexy is performed. warrant further therapy.
Fig. 24.19 Intraoperative photograph showing an ingui-

nal approach to undescended testis. Note the normal look-
ing testis Fig. 24.20 Clinical intraoperative photograph showing a
small atrophic testis. Note the intact vas and vessels
TESTIS
UTERUS
TESTIS
FALLOPIAN
TUBE
intraoperative
photograph of a patient
with bilateral
undescended testes. On
exploration, he was
found to have features of FALLOPIAN TUBE
persistent Mullerian duct
syndrome with uterus,
and fallopian tubes
24.10 Infertility and Undescended Testes 541
– In the presence of blind-ending vas and – Microvascular transplantation (83–96 %)

vessels or a testicular nubbin, the contralat- – Laparoscopic orchiopexy (80–95 %)
eral side should be explored and the testis – Laparoscopic Fowler-Stephens procedure
fixed trans-scrotal to prevent possible testis (Up to 96 %)
torsion on the other side.
– Intra-abdominal blind-ending vas and ves-
sels are found in 10 % of boys with nonpal- 24.9 Complications
pable testes. of Orchidopexy
– Orchiectomy is advocating for those with
small intra-abdominal testis or an abnor- • Testicular atrophy as a result of ischemic
mal testis. injury during dissection (5 %)
– The principal major complication of all • Failure of orchiopexy (8 % for palpable unde-
types of orchiopexy is loss of the blood scended testes and 25 % for those with intra-
supply to the testis, resulting in loss of the abdominal testes)
testis due to ischemic atrophy or fibrosis. • Injury to vas deferens (1–2 %)
• Length-increasing maneuvers: • Ascent of the testis (<10 %)
– The Prentiss maneuver involves rerouting • Epididymoorchitis
the cord under the epigastric vessels or the • Wound infection
division of epigastric vessels. • Bleeding and hematoma
– The internal inguinal ring can be opened to • Hydrocele
perform more complete retroperitoneal
mobilization.
– The Fowler-Stephens principle involves 24.10 Infertility and Undescended
dividing the testicular vessels to allow the Testes
blood supply to the vas deferens to keep the
undescended testis viable. The testicular • Men with undescended testes have reduced
vessels should be divided away from the fertility, even after orchiopexy in infancy.
testis. • The reported infertility rate in those with uni-
– Testicular autotransplantation can be per- lateral undescended testis is of about 10 %,
formed by transecting the testicular vessels when compared with about 6 % reported in the
and by performing a microvascular anasto- general population of adult men.
mosis to the inferior epigastric vessels. • The reported fertility reduction after orchido-
pexy for bilateral cryptorchidism is about
38 %, or six times that of the general
24.8.1 Success of Surgical Treatment population.
• To reduce this, early orchidopexy is recom-
• Orchiopexy for palpable testis has a success mended for these patients.
rate placing the testis in its normal intrascrotal • It was shown that delayed orchidopexy after
position in the range of 80–90 %. the second year of life will lead to degenera-
• The success rate of orchiopexy for nonpalpa- tion of spermatogenic tissue and reduced sper-
ble testis is variable depending on the tech- matogonia counts. There are several factors
nique used as follow: that contribute to this including exposure of the
– Inguinal approach (60–88 %) undescended testes to a higher temperature.
– Suprainguinal approach (Up to 95 %) • A factor contributing to infertility in those
– One-stage Fowler-Stephens procedure with cryptorchidism is the high rate of anoma-
(67–96 %) lies of the epididymis in these patients.
– Two-stage Fowler-Stephens procedure • Approximately 6 % of infertile men have a his-
(77–95 %) tory of orchiopexy or untreated cryptorchidism.
• The rate of infertility is higher in patients with general population and is approximately 1 in
bilateral cryptorchidism than in those with 80 with a unilateral undescended testis and 1 in
unilateral cryptorchidism or in the general 40 to 1 in 50 for bilateral undescended testes.
male population. The peak age for this tumor is 15–45 year.
• The paternity rate for patients with bilateral • To avoid delay in diagnosis of testicular
cryptorchidism is around 60 % versus 90 % in tumors, it is important to teach boys who had
patients with unilateral cryptorchidism. orchidopexy as infants to do testicular self-
• The paternity rate in those with unilateral examination and seek early medical advice
cryptorchidism is slightly less than the 94 % in when they feel testicular masses.
the general population. • This however is not the case for those with
• The location of the undescended testis may intra-abdominal testes where tumors are not
play a role in fertility potential. recognized before they reach a considerable
• Worsening testicular biopsy findings are cor- size or metastasize.
related with high locations of undescended • While orchidopexy may not protect patients
testis (e.g. intra-abdominal testis). from developing testicular malignancy, the
• Normal spermatogram findings are found in procedure allows for earlier detection through
20 % of patients with bilateral undescended self-examination of the testicles.
testis compared with 75 % of patients with • A mass developing in a scrotal testis following
unilateral cryptorchidism. orchidopexy is far easier to recognize than a
• The rate of germ-cell aplasia substantially mass in an intra-abdominal testis. Orchidopexy
increases after age 2 years. makes detection of testicular tumors easier.
• Semen quality may be impaired in men with a Orchidopexy however does not lower the risk
history of unilateral cryptorchidism. of developing testicular cancer.
• For men with a history of bilateral cryptorchi- • The most common tumor developing in an
dism, the prognosis for fertility is worse and undescended testis is a seminoma (65 %); but
this was not shown to improve by type or tim- following orchidopexy, seminomas represent
ing of treatment. only 30 % of testis tumors.
• The most common tumor in an undescended
testis is a seminoma, whereas the most com-
24.11 Undescended Testes mon tumor after successful orchiopexy is non-
and the Risk of Cancer seminomatous germ-cell tumor.
• Approximately 20 % of these tumors occur in
• It has been estimated that about 1 in 500 men a contralateral descended testis.
born with unilateral or bilateral undescended • Carcinoma in situ occurs in approximately
testes develop testicular cancer. 0.4 % of patients undergoing orchiopexy.
• In patients with cryptorchidism, the risk of • Orchiopexy is not protective against subse-
testicular cancer is 3–5 %, a four to sevenfold quent testis cancer but does place the testis in
greater risk than the 0.3–0.7 % reported in the a favorable position for routine self-
healthy population. examination, which is important in the early
• The peak incidence of testicular cancer occurs recognition of testicular cancer. The patient
in the third and fourth decades of life. and family must be educated about the risk of
• The risk of testicular cancer is higher for those future testicular cancer.
with intra-abdominal testes. • The risk of testicular cancer in men with a his-
• It has been estimated also that a normally tory of cryptorchidism:
descended testis of a man with undescended – There is a relative risk of 4.7 % in men with
testis on the other side has about a 20 % higher a history of cryptorchidism.
cancer risk than normal men. – This is essentially for intra-abdominal tes-
• The risk of malignancy in the undescended testicles, and this risk is not altered by
tis is four to ten times higher than that in the orchiopexy.
Further Reading 543
– Approximately 15–20 % of tumors also 11. Lee PA, Coughlin MT. Fertility after bilateral cryptor-
chidism. Evaluation by paternity, hormone, and
occur in the contralateral descended testis.
semen data. Horm Res. 2001;55(1):28–32.
– Most tumors occurring in testes after previ- 12. Lee PA, Coughlin MT. The single testis: paternity
ous successful orchiopexy are commonly after presentation as unilateral cryptorchidism. J Urol.
non-seminomatous germ cell tumors, while 2002;168(4 Pt 2):1680–2; discussion 1682–3.
13. Lee MM, Donahoe PK, Silverman BL, et al.
those arising in abdominal testes are most
Measurements of serum müllerian inhibiting sub-
frequently seminomas. stance in the evaluation of children with nonpalpable
gonads. N Engl J Med. 1997;336(21):1480–6.
14. Lee PA, O’Leary LA, Songer NJ, et al. Paternity after
bilateral cryptorchidism. A controlled study. Arch
Further Reading Pediatr Adolesc Med. 1997;151(3):260–3.
15. Lindgren BW, Darby EC, Faiella L, et al. Laparoscopic
1. Bassel YS, Scherz HC, Kirsch AJ. Scrotal incision orchiopexy: procedure of choice for the nonpalpable
orchiopexy for undescended testes with or without a testis? J Urol. 1998;159(6):2132–5.
patent processus vaginalis. J Urol. 2007;177(4): 16. Merry C, Sweeney B, Puri P. The vanishing testis:
1516–8. anatomical and histological findings. Eur Urol. 1997;
2. Chua ME, Mendoza JS, Gaston MJ, Luna Jr SL, 31(1):65–7.
Morales Jr ML. Hormonal therapy using gonadotro- 17. Miller KD, Coughlin MT, Lee PA. Fertility after uni-
pin releasing hormone for improvement of fertility lateral cryptorchidism. Paternity, time to conception,
index among children with cryptorchidism: a meta- pretreatment testicular location and size, hormone and
analysis and systematic review. J Pediatr Surg. sperm parameters. Horm Res. 2001;55(5):249–53.
2014;49(11):1659–67. 18. Penson D, Krishnaswami S, Jules A, McPheeters
3. Cortes D, Thorup JM, Visfeldt J. Cryptorchidism: ML. Effectiveness of hormonal and surgical therapies
aspects of fertility and neoplasms. A study including for cryptorchidism: a systematic review. Pediatrics.
data of 1,335 consecutive boys who underwent tes- 2013;131(6):e1897–907.
ticular biopsy simultaneously with surgery for crypt- 19. Pettersson A, Richiardi L, Nordenskjold A, Kaijser M,
orchidism. Horm Res. 2001;55(1):21–7. Akre O. Age at surgery for undescended testis and risk
4. Cuda SP, Srinivasan AK, Kalisvaart J, Kirsch AJ. of testicular cancer. N Engl J Med. 2007;356(18):
Evolution of single practice trends in the surgical 1835–41.
approach to the undescended testicle. J Urol. 20. Radmayr C, Oswald J, Schwentner C, Neururer R,
2011;185(6 Suppl):2451–4. Peschel R, Bartsch G. Long-term outcome of laparo-
5. Giannopoulos MF, Vlachakis IG, Charissis GC. 13 scopically managed nonpalpable testes. J Urol.
years’ experience with the combined hormonal ther- 2003;170(6 Pt 1):2409–11.
apy of cryptorchidism. Horm Res. 2001;55(1):33–7. 21. Rajfer J, Handelsman DJ, Swerdloff RS, et al.
6. Hutson JM, Southwell BR, Li R, Lie G, Ismail K, Hormonal therapy of cryptorchidism. A randomized,
Harisis G, et al. The regulation of testicular descent double-blind study comparing human chorionic
and the effects of cryptorchidism. Endocr Rev. gonadotropin and gonadotropin-releasing hormone. N
2013;34:725–52. Engl J Med. 1986;314(8):466–70.
7. Kim SO, Hwang EC, Hwang IS, et al. Testicular catch 22. Sharma S, Sen A. Complete testicular epididymal dis-
up growth: the impact of orchiopexy age. Urology. sociation in the abdominal cryptorchid testis. J Pediatr
2011;78(4):886–9. Urol. 2013;9:1023–7.
8. Kolon TF, Herndon CD, Baker LA, Baskin LS, 23. Tasian GE, Copp HL, Baskin LS. Diagnostic imaging
Baxter CG, Cheng EY, et al. Evaluation and treat- in cryptorchidism: utility, indications, and effective-
ment of cryptorchidism: AUA guideline. J Urol. ness. J Pediatr Surg. 2011;46(12):2406–13.
2014;192(2):337–45. 24. Thorsson AV, Christiansen P, Ritzen M. Efficacy and
9. Kolon TF, Herndon A, Baker LA, et al. Evaluation safety of hormonal treatment of cryptorchidism: cur-
and treatment of cryptorchidism: AUA guideline. rent state of the art. Acta Paediatr. 2007;96(5):
J Urol. American Urological Association. Published 628–30.
online May 20, 2014. Available at http://www.jurol- 25. Toppari J. Physiology and disorders of testicular
ogy.com/article/S0022-5347(14)03531-9/fulltext. descent. Endocr Dev. 2003;5:104–9.
10. Law GS, Perez LM, Joseph DB. Two-stage Fowler- 26. Wood HM, Elder JS. Cryptorchidism and testicular
Stephens orchiopexy with laparoscopic clipping of the cancer: separating fact from fiction. J Urol.
spermatic vessels. J Urol. 1997;158(3 Pt 2):1205–7. 2009;181(2):452–61.
Varicocele
25
25.1 Introduction • Upward flow of blood in the veins is ensured

by small one-way valves that prevent
• The testes are supplied by blood vessels that backflow.
originate in the abdomen and course down • A varicocele is an abnormal enlargement and
through the inguinal canal as part of the sper- tortuosity of the pampiniform plexus of veins
matic cord to the testis. (Fig. 25.1).
• The testis is drained by a plexus of veins • Varicoceles result from defective valves, or
called the pampiniform venous plexus. These compression of the vein by a nearby structure.
course upward and coalescence to form the This leads to dilatation of the testicular veins
testicular vein. The left testicular vein drains and the formation of a varicocele.
at right angle into the left renal vein while the • The true incidence of adolescent varicoceles is
right testicular vein drains directly into the not known because most adolescent varico-
inferior vena cava. celes are asymptomatic.
DILATED, TORSIOUS
PAMPINEFORM PLEXUS
TESTIS
Fig. 25.1 Diagram-
of a varicocele

546 25 Varicocele
• The initial presentation of varicoceles usually – This is because the left testicular vein
occurs during puberty, with an incidence in drains into the left renal vein (at a 90-degree
13-year-old adolescent boys equal to that of angle), while the right testicular vein drains
adult men (15 %). directly into the inferior vena cava.
• Rarely, varicoceles are noted in the prepuber- – Isolated right sided varicoceles are rare.
tal period. – Increased length of the left testicular vein:
• Although varicoceles may be bilateral, they • The left vein is 8–10 cm longer than the
are usually unilateral and almost always on right testicular vein. This may contrib-
the left side. ute to an increased pressure in the left
• It has been estimated that 90 % of all varico- testicular vein when compared to the
celes occur on the left side. This is attributed right testicular vein.
to the fact that the right testicular vein drain • Secondary varicocele:
directly into the inferior vena cava while the – This results from compression of the
left testicular vein drains at a right angle into venous drainage of the testicle.
the left renal vein. This predisposes to slower – This can develop as a result of pelvic or
drainage in the left testicular vein. abdominal tumors that causes compression
• A unilateral right-side varicocele raises certain of the veins draining the testes.
concerns and should prompt an investigation – A unilateral right-sided varicocele that is
for an underlying obstructive cause such as: newly diagnosed in a patient older than
– A tumor 40 years of age should raise the possibility
– Retroperitoneal fibrosis of an underlying malignancy.
– Thrombosis or occlusion of the inferior – The most common cause is renal cell carci-
vena cava noma (hypernephroma) followed by retro-
• These patients should be investigated radio- peritoneal fibrosis or adhesions.
graphically including computed tomography – In the pediatric age group, left-sided
(CT). Wilms’ tumor with extension into the renal
• Situs inversus is another rare cause of a right- vein can cause obstruction of the testicular
side varicocele which must be kept in mind. vein leading to left varicocele. In those
with right-sided Wilms’ tumor, a varicocele
can develop if the tumor extends into the
25.2 Etiology inferior vena cava and leads to obstruction
of the right renal vein.
• The exact etiology of varicoceles is unknown – “The Nutcracker syndrome”:
and various theories have been proposed to • This is one non-malignant causes of a
explain this taking in consideration the fact that secondary varicocele.
90 % of all varicoceles occur on the left side. • In this condition, the superior mesenteric
• Varicoceles are divided into two types depend- artery compresses the left renal vein
ing on the etiology. between it and the aorta, causing increased
– Primary or idiopathic varicocele pressures which is transmitted retrograde
– Secondary varicocele into the left pampiniform plexus of veins.
• Primary or idiopathic varicocele:
– This is the commonest type.
– It occurs as a result of defective valves 25.3 Pathophysiology
within the veins along the spermatic cord.
– This results in backflow of blood into the • The pampiniform plexus of veins is the net-
pampiniform plexus and causes its dilata- work of veins that normally drain the testicle.
tion, tortuosity and increased pressures. • Normally, the size of the veins that make up
– The majority of idiopathic varicoceles the pampiniform plexus range from 0.5 to
occur on the left side. 1.5 mm
25.4 Grading of Varicoceles 547
• This plexus of veins travels along the posterior – The subsequent effects of a varicocele on
portion of the testicle with the epididymis and semen include:
vas deferens, and then into the spermatic cord • Decreased sperm motility
and upwards where they coalesces to form the • Lower total sperm counts
testicular vein. • Increased number of abnormal sperm
• Upward flow of blood in the veins is ensured forms
by small one-way valves that prevent • These changes may be reversed with correc-
backflow. tive surgery.
• The right testicular vein drains into the infe- • The reasons for altered sperm production, tes-
rior vena cava, while the left testicular vein ticular size, and morphologic changes in the
drains into the left renal vein at right angle to testis are not clearly understood. The proposed
the renal vein, which then drains into the infe- pathophysiologic mechanisms include the
rior vena cava. followings:
• The pampiniform plexus of veins not only – The dilated veins in the pampiniform
drains the blood from the testes, vas and epi- plexus with pooling of venous blood results
didymis but also has an important function to in increased scrotal and testicular
lower the temperature of the testes. temperature.
• A varicocele develops when there is dilatation – The increase in testicular temperature will
and tortuosity of the veins of the pampiniform lead to morphologic changes in sperm and
plexus. testicular tissue.
• It has been estimated that a varicocele devel- – It is suggested that the renal and adrenal
ops when the size of these veins exceeds metabolites that reflux into dilated sper-
2 mm. matic veins affect testicular tissue leading
• The development of a varicocele with these impaired spermatogenesis and compro-
dilated veins leads to an increase in the tem- mised testicular hormone production and
perature around the testes resulting in testicu- function.
lar atrophy, reduction in the quality and the – The low oxygen tension in the dilated veins
quantity of the sperms and infertility. This of the testis may result in local tissue
effect on sperm quantity and quality is hypoxia which could also affect both tes-
progressive. ticular function and sperm production.
• It has been shown also that blood from the – As a result of this, there will be a paracrine
testes that cannot drain via the pampiniform imbalances in the testicle which may lead
plexus may drain via communicating vessels to impaired testicular function.
through the prostate. The increased flow of
blood to the prostate can lead to congestion
and enlargement of the prostate gland sec- 25.4 Grading of Varicoceles
ondary to cell proliferation resulting from
the high concentration of free testosterone • Dubin and Amelar graded varicoceles into
reaching directly from the testes to the four grades based on physical examination
prostate. findings as follows:
• It has been shown that a varicocele that per- – Grade 0:
sists will lead to histopathological changes in • This is a subclinical varicocele which
the testis which include: cannot be detected during physical
– The affected testis is abnormally small as examination and diagnosed with ultra-
compared with the contralateral testis. sonography or venography
– Seminiferous tubule sclerosis – Grade 1:
– Small vessel degenerative changes • This is detected clinically with difficulty
– Abnormalities of Leydig, Sertoli, and germ (<1 cm) and increases in size with
cells Valsalva maneuver
548 25 Varicocele
– Grade 2: – Dragging-like or aching pain within

• This is easily detected without Valsalva scrotum
maneuver (1–2 cm) – Feeling of heaviness in the testicle
– Grade 3: – Atrophy of the testicle
This a large varicocele that is palpable and • There may be a difference in testicular sizes
can be seen from a distance (>2 cm) without a palpable varicocele.
• The degree of testicular atrophy correlates • Varicoceles may present as an incidental find-
with the varicocele grade. ing on scrotal ultrasonography done for other
• No patients with grade 1 varicoceles were reasons.
noted to have testicular atrophy while 80 % • Varicoceles are considered as one of the lead-
with grade 3 and 30 % with grade 2 varico- ing causes of adult male infertility and are
celes have testicular atrophy. detected in 35 % of adult males with primary
infertility.

25.6 Diagnosis
• Varicoceles are most frequently diagnosed
when a patient is 13–30 years of age, and • The diagnosis of a varicocele is made
rarely develop after the age of 40. clinically.
• They are reported to occur in 15–20 % of all • This is made by carefully palpating the scro-
males. tum while the patient is standing.
• The prevalence of varicoceles in individuals • Sometimes, the distended veins can be seen on
aged 10–19 years is reported to be approxi- the lateral aspect of the scrotum.
mately 15 % and is similar to the prevalence • A small varicocele may feel like a thickened
reported for adults. spermatic cord.
• Varicoceles are extremely rare in patients • A larger varicocele feels like a bag of worms.
younger than 9 years (Fig. 25.2) • A varicocele is a non-tender mass.
• The vast majority of varicoceles are • When the patient is asked to perform a
asymptomatic. Valsalva maneuver, the veins of the pampini-
• Varicoceles mat present with: form plexus becomes more distended and
– Testicular pain accentuates the physical findings.
– A scrotal mass • When the patient is asked to lie down, gravity
– Acute or chronic scrotal discomfort may allow the drainage of the pampiniform
– Visible or palpable enlarged vein plexus and thus make the mass smaller and
DILATED,
TORSIOUS
PAMPINEFORM
PLEXUS

photograph of a child with
left varicocele
25.7 Treatment 549
not obvious. This is especially true in primary • A semen analysis may be done in infertile
varicocele, and if the varicocele does not patients preoperatively as a base line which
become smaller, this is a sign for clinical con- can be compared to the results postoperatively
cern and an obstructive etiology should be which are expected to show improvements in
considered. semen analysis parameters.
• Both testes should be palpated and the testicle
on the side of the varicocele may or may not
be smaller when compared to the other side. 25.7 Treatment
• It has been suggested that the testicular size
should be assessed with an orchidometer. This Indications of Treatment
is a reliable method of assessing testicular size • There are no clear indications for surgical treat-
but ultrasonography is more reliable. A ment of varicocele in children and adolescents.
Doppler ultrasound not only demonstrate the • Varicocele associated with testicular growth
varicocele but also can see blood reverse retardation. These patients are likely to mani-
direction in a varicocele with a Valsalva fest impaired fertility in adulthood.
maneuver. • Symptomatic painful varicocele.
• There are two formulas used to calculate tes- • A clinically evident varicocele and poor
ticular volume based on measurements semen quality.
obtained via ultrasonography: • A palpable varicocele with testicular atrophy
– The Lambert formula: and semen abnormality. A 20 % volume deficit
• Testicular volume = Length × width × in the affected testes is considered an indica-
depth × 0.71 tion for surgical intervention.
– The volume of rotational ellipsoid • Bilateral varicoceles
formula: • Grade 2 or 3 varicocele
Two variations exist for the volume of rota-
tional ellipsoid formula: Medical Treatment
• Testicular volume = Length × width × • L-carnitine has some beneficial effect on sperm
depth × 0.52 parameters, but it is not as effective as surgery.
• Testicular volume = Length × width2 × • Micronised purified flavonoid fractions (MPFF)
0.52 (Daflon) have a beneficial effect on reducing
– The average volume of the male testis is varicocele pain and reducing reflux time of left
23 ± 3 cm3. spermatic vein during the Valsalva maneuver.
– A size difference of more than 3 cm3 is
considered significant. Embolization Therapy
• Recent studies have shown that varicocele is • An alternative to surgery is embolization.
usually a bilateral disease. The diagnosis of • This is a minimally invasive treatment that
the right side is usually missed clinically and involves passing a small wire through a
an ultrasonography with a color flow Doppler peripheral vein and into the abdominal veins
should be performed to detect a subclinical that drain the testes.
right varicocele. • Embolization materials include balloons,
• Computed tomography (CT) is rarely indi- coils, and dextrose.
cated but may be useful in those with an iso- • Embolization is an effective treatment for
lated right-side varicocele or a secondary recurrent post-surgical varicoceles.
obstructive varicocele. This is to exclude a
renal or other retroperitoneal mass or throm- Anatomy
bosis of the inferior vena cava. • The spermatic cord extends upward from the
• Venography is rarely used to detect a subclini- testis into the inguinal region, above the
cal varicocele in an infertile adult patient. scrotum.
550 25 Varicocele
• The spermatic cord contains: testicular atrophy because of the collateral

– The spermatic veins circulation to the testis. This latter technique
– The vas deferens relies on the vasal artery as the main blood
– The testicular arteries, including the inter- supply to the testis.
nal spermatic artery (may be multiple
branches)
– The vasal artery 25.8 Postoperative Complications
– The external spermatic artery.
• Above the inguinal region, the vas, with its • Surgical treatment of varicocele is known to
arterial supply, diverges from the internal be associated with postoperative complica-
spermatic artery and veins, which course tions. The frequency of these complications is
through the retroperitoneum, along the psoas variable depending on the surgical approach
muscle. used.
• A varicocele is situated in the upper scrotum, • The microscopic-assisted procedures carry the
above the testis. lowest complication rates (<1 %).
• The left testicular vein drains into the left • Hydrocele formation is the most common
renal vein while the right testicular vein drains complication of varicocelectomy and most
directly into the inferior vena cava. likely results from lymphatic obstruction.
• Percutaneous embolization is very infre-
Surgical Treatment quently associated with hydrocele formation
• Varicocelectomy (Surgical ligation of the but can cause contrast reactions, puncture of
spermatic veins) is the procedure of choice to the femoral artery, hemorrhage, extravasation,
treat varicoceles. and migration of embolization balloons.
• Several approaches are used, differing primar- • These complications include:
ily in the level at which the vessels are ligated. – Hematoma
These include: – Hydrocele
– Abdominal retroperitoneal (Palomo) – Infection
approach – Testicular atrophy
– Inguinal (Ivanissevitch) approach – Injury to the scrotal tissue or structures
– Sub inguinal approach – Recurrence or persistence of the
– Recently, microsurgical techniques and varicocele
laparoscopic-assisted transperitoneal or – Injury to the vas deferens
retroperitoneal approaches are used. – Chronic testicular pain
• With the inguinal and sub inguinal approaches, – Injury to the artery that supplies the
the testicular artery is generally spared using a testicle
microscope. Visualization of the testicular • The frequency of recurrence depends on the
artery can be ascertained using papaverine or approach used.
lidocaine administration or using a Doppler – Embolization has an 80–90 % success rate
probe intraoperatively. Lymphatic vessels are and a recurrence rate of approximately
also preserved when possible to prevent future 10–25 %.
hydrocele formation. – The microsurgical approach has a varico-
• When surgery is performed in the retroperito- cele recurrence less than 5 % of cases and
neum or transperitoneally, some authors less than 1 % hydrocele development.
advocate dividing both the testicular artery – The inguinal, retroperitoneal, and laparo-
and the veins to avoid missing any venous scopic approaches have a 13–16 % recur-
branches. Ligation of the internal spermatic rence rate and a 7–9 % risk of hydrocele
artery in this approach does not usually cause development.
Further Reading 551
25.9 Prognosis 5. Kass EJ. The adolescent varicocele: treatment and

outcome. Curr Urol Rep. 2002;3(2):100–6.
6. Kass EJ, Marcol B. Results of varicocele surgery in
• Varicocele can be harmless, but in some cases adolescents: a comparison of techniques. J Urol.
it can cause infertility and testicular pain. 1992;148(2 Pt 2):694–6.
• Surgical treatment of varicocele may improve 7. Kubal A, Nagler HM, Zahalsky M, Budak M. The
adolescent varicocele: diagnostic and treatment pat-
fertility and there are reports showing
terns of pediatricians. A public health concern? J Urol.
improvement in sperm quality following sur- 2004;171(1):411–3.
gery in 57 % of patients. 8. Lemack GE, Uzzo RG, Schlegel PN, Goldstein
• Varicocelectomy improves sperm parameters M. Microsurgical repair of the adolescent varicocele.
J Urol. 1998;160(1):179–81.
and testicular volume. These improvements
9. Lund L, Tang YC, Roebuck D, et al. Testicular catch-
include: up growth after varicocele correction in adolescents.
– Total sperm count Pediatr Surg Int. 1999;15(3–4):234–7.
– Sperm motility 10. Nees SN, Glassberg KI. Observations on hydroceles
following adolescent varicocelectomy. J Urol. 2011;
– Sperm density
186(6):2402–7.
– Sperm morphology 11. Pini Prato A, MacKinlay GA. Is the laparoscopic
– Reduces sperm DNA damage and seminal Palomo procedure for pediatric varicocele safe and
oxidative stress effective? Nine years of unicentric experience. Surg
Endosc. 2006;20(4):660–4.
12. Pinto KJ, Kroovand RL, Jarow JP. Varicocele related
testicular atrophy and its predictive effect upon fertil-
Further Reading ity. J Urol. 1994;152(2 Pt 2):788–90.
13. Reyes BL, Trerotola SO, Venbrux AC, et al.
1. Al-Kandari AM, Shabaan H, Ibrahim HM, Elshebiny Percutaneous embolotherapy of adolescent varico-
YH, Shokeir AA. Comparison of outcomes of different cele: results and long-term follow-up. J Vasc Interv
varicocelectomy techniques: open inguinal, laparo- Radiol. 1994;5(1):131–4.
scopic, and subinguinal microscopic varicocelectomy: a 14. Rizkala E, Fishman A, Gitlin J, Zelkovic P, Franco
randomized clinical trial. Urology. 2007;69(3):417–20. I. Long term outcomes of lymphatic sparing laparo-
2. Hadziselimovic F, Herzog B, Jenny P. The chance for scopic varicocelectomy. J Pediatr Urol. 2013;9(4):
fertility in adolescent boys after corrective surgery for 458–63.
varicocele. J Urol. 1995;154(2 Pt 2):731–3. 15. Sayfan J, Siplovich L, Koltun L, Benyamin
3. Hassan JM, Adams MC, Pope JC, et al. Hydrocele N. Varicocele treatment in pubertal boys prevents tes-
formation following laparoscopic varicocelectomy. ticular growth arrest. J Urol. 1997;157(4):1456–7.
J Urol. 2006;175(3 Pt 1):1076–9. 16. Skoog SJ, Roberts KP, Goldstein M, Pryor JL. The
4. Iselin CE, Almagbaly U, Borst F, et al. Safety and effi- adolescent varicocele: what’s new with an old prob-
ciency of laparoscopic varicocelectomy in one hun- lem in young patients? Pediatrics. 1997;100(1):
dred consecutive cases. Urol Int. 1997;58(4):213–7. 112–21.
Testicular Torsion and Torsion
of the Testicular or Epididymal 26
Appendage
26.1 Introduction • The most common underlying cause is a con-

genital malformation known as a “bell-clapper
• Acute scrotal pain requires immediate surgi- deformity”.
cal attention to determine the underlying • This congenital anomaly is results in the long
cause and to treat accordingly. axis of the testicle becoming oriented trans-
• The diagnosis of acute scrotal pain may not be versely rather than cephalocaudal.
straightforward and in some patients, immedi- • In this malformation, the testis is inadequately
ate surgical exploration may be necessary in affixed to the scrotum allowing it to move
order to treat torsion of the testes early to freely on its axis which can lead to twisting of
achieve good results. the cord and its vessels.
• Acute scrotal pain and swelling in children • In the “bell-clapper deformity”, the testis
and young adults indicates torsion of the testis hangs within the scrotum and can swing like a
until proven otherwise. bell clapper in a bell, allowing for easy tor-
• In approximately two thirds of patients, his- sion. Males born with the bell clapper defor-
tory and physical examination are sufficient to mity have no attachments around either
make an accurate diagnosis. testicle, so that torsion can potentially occur
• Testicular torsion is a true surgical emergency on either side (Fig. 26.1).
and must be differentiated from other com- • Bilateral testicular torsion, however, is an
plaints of testicular pain because a delay in exceedingly rare event.
diagnosis and management can lead to loss of • Testicular torsion occurs more commonly in
the testicle. patients who have an inappropriately high
• Testicular torsion may interrupt blood flow to attachment of the tunica vaginalis. This allows
the testis and epididymis. the testicle to rotate freely on the spermatic
• The degree of testicular torsion is however cord within the tunica vaginalis (intravaginal
variable varying from 180 to 720°. testicular torsion).
• Testicular torsion accounts for about 26 % of • The bell clapper deformity is present in
cases of acute scrotum. approximately 12 % of males; 40 % of them
• It occurs when the spermatic cord twists lead- are affected in both testicles.
ing to testicular ischemia and necrosis as a • It has been estimated that irreversible isch-
result of cutting off the testicle’s blood emia and necrosis of the testis begins around
supply. six hours after the onset of torsion.

554 26 Testicular Torsion and Torsion of the Testicular or Epididymal Appendage

bell-clapper deformity.
This allows the testicle to
rotate freely on the
spermatic cord within the
tunica vaginalis and
predisposes to intravaginal
torsion of testis
TUNICA
VAGINALIS
EPIDIDYMIS
TESTIS
• This calls for early diagnosis and emergency

correction of torsion to minimize the risk of 26.2 Etiology and Risk Factors
testicular infarction.
• The diagnosis of testicular torsion is clinical • The exact etiology of testicular torsion is not
and if doubt an emergency Doppler ultrasound known
can be done. • The “bell-clapper deformity”
• Testicular torsion commonly develops during – This is the commonest cause of testicular
puberty but can also be seen in newborns as a torsion
result of intrauterine torsion or soon after – It accounts for 90 % of the cases
birth. – It is a congenital malformation of the pro-
• The exact incidence of testicular torsion is not cessus vaginalis
known but it has been estimated to occur in – In this condition, rather than the testes
about 1 in 4,000 to 1 in 25,000 males per year attaching posteriorly to the inner lining of
before 25 years of age. the scrotum by the mesorchium, the mesor-
• Testicular torsion is most frequent among ado- chium terminates early and the testis is free
lescents with about 65 % of cases presenting floating in the tunica vaginalis.
between 12 and 18 years of age. – This condition is bilateral and calls for fix-
• It has been estimated that in 95 % of men with ation of the other testis when one testis is
testicular torsion the testis can be saved if affected. This is to prevent subsequent tor-
treated within six hours of the onset of pain. sion of the other side.
• Other causes of acute scrotal pain that should • A large mesentery between the epididymis
be ruled out include: and the testis can also predispose itself to tor-
– Orchitis sion, although this is rare.
– Epididymitis, epididymo-orchitis • Contraction of the spermatic muscles shortens the
– Torsion of the testicular or epididymal spermatic cord and may initiate testicular torsion.
appendages • Other etiologic factors involved in intravagi-
– Trauma-related causes of acute scrotum nal testicular torsion include:
– Acute hydrocele – Undescended testicle
– Testicular tumor – Sexual arousal or activity
– Idiopathic scrotal edema – Physical exercise
26.3 Diagnosis 555
– An active cremasteric reflex

– Cold weather.
• A larger testicle either due to normal variation
or a tumor increases the risk of torsion.
26.3 Diagnosis
• The diagnosis of testicular torsion is clinical

based on the history and presenting signs and
symptoms.
• With a convincing history and physical exam-
ination, no time should be wasted on investi-
gations and immediate surgical exploration
should be done.
• Doppler ultrasound should be done only in
low suspicion cases to rule out torsion and dif-
ferentiate this from epididymo-orchitis.
Doppler ultrasonography can be used to dem-
onstrate arterial blood flow to the testis while
providing information about other testicular
pathology. It is about 90 % accurate in diag- Figs. 26.2 and 26.3 A Doppler ultrasound showing
nosing testicular torsion. bilateral torsion of testes
– In testicular torsion, there is no blood flow
or the blood flow is markedly decreased.
– In epididymo-orchitis, there is normal or 90–100 % accuracy in detecting testicular
slightly increased blood flow. blood flow.
– The sensitivity of color Doppler in – This is the most accurate investigation but
detecting acute testicular torsion in chil- it is not readily available
dren is 90–100 %, with specificity being – Add to this the time it requires to organize
100 %. and do this investigation particularly in
– Other studies have suggested that color cases of torsion where urgency is
Doppler ultrasonography was only 86 % required
sensitive, 100 % specific, and 97 % accu- – In testicular torsion, there is no uptake
rate in the diagnosis of testicular torsion of the uptake is markedly reduced
(Figs. 26.2 and 26.3). – In epididymo-orchitis, there is normal
– Doppler ultrasonography has (Figs. 26.4 uptake and uniformly symmetric
and 26.5): activity.
• 94 % sensitivity. – A urine analysis and culture can be done to
• 96 % specificity. roll out infection.
• 95.5 % accuracy. – The complete blood count can be normal.
• 89.4 % positive predictive value. However, the WBC count is elevated in as
• 98 % negative predictive value. many as 60 % of patients who have testicu-
• In doubtful cases, an isotope scan (techne- lar torsion.
tium-99 m pertechnetate) can be done. • Surgical exploration should not be delayed for
Radionuclide scans have a sensitivity of the sake of performing imaging studies.
Figs. 26.4 and 26.5

A Doppler ultrasound
showing epididymitis.
Note the enlarged left
epididymis and the good
blood flow to the testis
26.4 Intermittent Testicular • Testicular torsion is also classified anatomi-

Torsion cally into two types:
– Intravaginal torsion
• This is a less serious variant of testicular torsion. • This is the commonest type
• It is a chronic condition characterized by the • Commonly develops during puberty
symptoms of testicular torsion but followed • The torsion occurs within the tunica
by eventual spontaneous detortion and resolu- vaginalis
tion of pain. • Intravaginal torsion comprises approxi-
• The attack may be associated with nausea or mately 16 % of patients with torsion
vomiting presenting in emergency departments
• These patients are however at significant risk with acute scrotum.
of developing complete torsion • Thepeak incidence occurs in adoles-
• It is important recognize this condition and cents aged 13 years.
physicians treating these patients should be • The left testis is more frequently
aware of this. involved.
• The treatment is elective bilateral orchiopexy. • Bilateral cases account for 2 % of all
• This is curative and 97 % of patients who testicular torsions.
undergo bilateral orchidopexy experience – Extravaginal torsion (Figs. 26.6, 26.7,
complete relief from their symptoms. 26.8, 26.9, and 26.10)
• This much less common
• Extravaginal torsion comprises approxi-
26.5 Classification of Testicular mately 5 % of all testicular torsions.
Torsion • This type occurs exclusively in newborns
• The condition is most often a prenatal
• Testicular torsion is classified is classified into (in utero testicular torsion) event.
two types depending on onset: • It is associated with high birth weight.
– Acute testicular torsion • Up to 20 % of cases are synchronous,
– Intermittent testicular torsion and 3 % are asynchronous bilateral.
26.6 Effects of Testicular Torsion 557
• This type of torsion occurs outside of • It is usually unilateral but can also occur
the tunica vaginalis, when the testis and bilaterally.
gubernaculum can rotate freely. • The newborns with this type of torsion
• The torsion usually occurs intrauterine usually present immediately after birth
and rarely soon after birth with scrotal swelling, and dark discolor-
ation of the scrotum
• Clinically, the affected testis is usually
firm and painless
• The scrotal skin characteristically fixes
to the necrotic gonad.
• The affected testis is usually necrotic
• The treatment is orchidectomy and con-
tralateral orchidopexy to obviate the
risk of torsion on the other side
26.6 Effects of Testicular Torsion
• Torsion of the testes causes venous occlusion

and engorgement as well as arterial obstruc-
tion and ischemia and subsequent infarction
of the testis. The extent of this depends on two
factors:
– The degree of torsion:
• Torsion of testis occurs as the testis and
the cord rotate between 90° and 180°,
Fig. 26.6 A clinical photograph showing a newborn with
intrauterine torsion of testis. Note that the patient is compromising blood flow to and from
healthy and of good weight the testis.
Figs. 26.7, 26.8, and 26.9 Clinical and intraoperative photographs showing intrauterine torsion of testes. Note the
discoloration of the affected scrotum which is slightly elevated. Note also the frankly necrotic testis

representation of the two
types of testicular torsion, INTRAVAGINAL EXTRAVAGINAL
the intravaginal and TORSION TORSION
extravaginal torsions
• Complete testicular torsion usually occurs 26.7 Clinical Features

when the testis twists 360° or more.
• Incomplete or partial torsion occurs • Although testicular torsion can occur at any age,
with lesser degrees of rotation. including the prenatal and perinatal periods, it
• In some cases, the degree of testicular most commonly occurs in adolescent males.
torsion may extend to 720°. • Testicular torsion is commonly observed in
– The duration of torsion: males younger than 30 years, with a peak at
• The duration of testicular torsion is the 12–18 years.
most important factor that prominently • The incidence of testicular torsion in males
influences the salvage rates of the affected younger than 25 years is approximately 1 in
testis and late testicular atrophy. 4,000.
• Testicular salvage is most likely if the • Testicular torsion more often involves the left
duration of torsion is less than 6 h. testicle.
• If 24 h or more elapse, testicular necro- • Testicular torsion can occur suddenly, with
sis develops in most patients. physical activity or may develop during sleep.
• Torsion can occur:
– Spontaneously
The Duration of Torsion and Testicular – During sports or physical activity
Salvage Rate – In relation to trauma in 4–8 % of cases
• <6 h: 90–100 % – During sleep
• 12–24 h: 20–50 % • This is an acute emergency and the patient
• >24 h: 0–10 % usually present with:
– The classic presentation of testicular tor-
sion is the sudden onset of severe testicular
pain followed by inguinal and/or scrotal
• The decreased fertility observed in patients swelling.
who developed only unilateral torsion of the – Gradual onset of pain is an uncommon pre-
spermatic cord, was based on an inherent sentation of testicular torsion.
bilateral testicular abnormalities or an autoim- – The pain may lessen as the necrosis
mune mechanism affecting the contralateral becomes more complete.
testis. This hypothesis however was not – This may be associated with groin and
supported. lower abdominal pain and tenderness
– In time, a reactive hydrocele, scrotal wall

erythema, and ecchymosis become more
striking.
– Scrotal pain that is referred to the lower
abdomen may be perceived as not being of
scrotal or testicular origin which is one of
the causes of delay in seeking early medi-
cal advice. Any adolescent boy who com-
plains of lower abdominal pain should also
undergo examination of the external
genitalia to rule out the possibility of scro-
tal or testicular pathology.
– The pain is often associated nausea and
vomiting. Approximately one third of
patients also have gastrointestinal upset
with nausea and vomiting. Fig. 26.11 A clinical photograph showing severe
– In the pediatric age group, nausea and epididymo-orchitis with intra-scrotal abscess formation in
a child
vomiting has a positive predictive value of
greater than 96 %.
– Patients rarely report voiding difficulties or – Fever is uncommon.
painful micturation. – Scrotal erythema.
– In some patients, scrotal trauma or other • The cremasteric reflex is almost always absent
scrotal disease (including torsion of appen- or diminished on the affected side in patients
dix testis or epididymitis) may precede the with testicular torsion. Normally, pinching the
occurrence of subsequent testicular inside of the thigh causes the testicles to con-
torsion. tract and move up. This reflux may disappear
– Patients may describe previous episodes of on the affected side
recurrent acute scrotal pain that has • Prehn’s sign: Relief of pain with elevation of
resolved spontaneously. This history is the testis. This is a classic physical examina-
highly suggestive of intermittent torsion tion sign but it is not reliable in distinguishing
and detorsion of the testis. testicular torsion from other causes of acute
– Acute testicular torsion developed in 10 % scrotal pain.
of patients with intermittent torsion while • Although a negative Prehn sign is classically
they waited for surgery. thought to be a predictor of torsion, this is
– Clinically, the affected testis will be swol- unreliable for diagnosis.
len, and markedly tender • The most confusing condition with
– The affected testis lies high up from its nor- torsion of testis is epididymo-orchitis. In
mal position usually with an abnormal epididymo-orchitis:
transverse lie – There is marked redness and swelling of the
– There may be redness of the affected affected testis
scrotum – The patient is often febrile
– There may be an associated mild fever – The cremasteric reflux is usually present
• Physical examination may reveal: • Epididymitis, orchitis, epididymo-orchitis
– A swollen, tender, high-riding testis. (Fig. 26.11):
– Abnormal transverse lie of testis. – These conditions most commonly occur
– Loss of the cremasteric reflex. from the reflux of infected urine or from
– Edema involving the entire scrotum. sexually acquired disease caused by gono-
– Enlargement and edema of the testis. cocci and Chlamydia.
– The patients occasionally develop these • It has been estimated that about 40 % of tes-
conditions following excessive straining or ticular torsion cases result in loss of the
lifting and the reflux of urine (chemical testicle.
epididymitis). • The success of salvaging the affected testis is
– These conditions may be secondary to an time dependent:
underlying congenital, acquired, structural, – If the affected testis is treated either manu-
or urologic abnormality and are often ally or surgically within 6 h, there is a high
accompanied by systemic signs and symp- chance (approx. 90 %) of saving the
toms associated with urinary tract infec- testicle.
tion. These include: – If the affected testis is treated at around
• Pyuria 12 h from the onset, the success rate of sal-
• Bacteriuria vaging the testis decreases to 50 %.
• Leucocytosis – If the affected testis is treated about 24 h
– A complete urological evaluation (ie, renal from the onset, the success rate of salvag-
sonography, urodynamic study) is neces- ing the testis drops to 10 %.
sary in prepubertal boys with acute – If the affected testis is treated after 24 h
epididymitis. from the onset, the ability to save the testi-
• In an acute developing hydrocele: cle approaches 0.
– The swelling is usually painless but there • Typically when testicular torsion occur, the
may be some discomfort testis rotates towards the midline of the body.
– The scrotal contents can be visualized with • Non-surgical correction of testicular torsion
transillumination (manual detorsion):
– Incarcerated hernia if suspected may be – This can sometimes be accomplished by
diagnosed by careful examination of the manually rotating the testicle in the oppo-
inguinal canal site direction (i.e., outward, towards the
• In idiopathic scrotal edema: thigh). Rotate the testis in medial to lateral
– In idiopathic scrotal edema, the scrotal skin direction.
is thickened, edematous, and often – This maneuver can be attempted while
inflamed. waiting for proper surgical exploration but
– The testis is not tender and is of normal no further time should be wasted.
size and position. – This is usually difficult because of acute
• Factors predictive of testicular torsion include: pain during manipulation.
– Acute onset of pain. – The procedure for manual detorsion of the
– Duration of pain of less than 6 h. testis is similar to the “opening of a book”
– Fever, nausea and vomiting. when the physician is standing at the
– History of trauma or activities. patient’s feet.
– Absence of cremasteric reflex. – Most torsions twist inward and toward the
– Abnormal transverse direction of testis. midline (anti-clock wise rotation); thus,
manual detorsion of the testicle involves
twisting outward and laterally (anti-clock
26.8 Treatment wise).
– Torsion closes the book and manual detor-
• Testicular torsion is an acute surgical emer- sion opens the book.
gency and with early diagnosis and prompt – Lateral rotation has been described in up to
treatment the testicle can often be saved. a third of testicular torsions, however, and
• The aim is to restore the blood flow to the in such cases further lateral rotation will
affected testis as early as possible. worsen the condition.
26.8 Treatment 561
– For manual detorsion in a suspected torsion – A bilateral scrotal orchidopexy is often rec-
of the right testicle, the physician is posi- ommended to treat the torsed testis and
tioned in front of the standing or supine prevent torsion of the other testis.
patient and holds the patient’s right testicle • The treatment of testicular torsion is emer-
with the left thumb and forefinger. The gency surgical exploration (surgical
physician then rotates the right testicle out- detorsion).
ward 180° in a medial-to-lateral direction. – This done through a scrotal approach.
– For the patient’s left testicle torsion, the phy- – If the testis is found viable, it should be
sician uses the right thumb and forefinger fixed (orchidopexy) and contralateral
and rotates the patient’s left testicle in an out- orchidopexy should be done at the same
ward direction 180° from medial to lateral. time.
– Rotation of the testicle may need to be – If the testis is found necrotic, orchidectomy
repeated two to three times for complete should be done and contralateral orchido-
detorsion. pexy is done at the same time.
– Pain relief serves as a guide to successful • Patients requiring an orchiectomy because of
detorsion, but restoration of blood flow a nonviable testis may benefit from the place-
using Doppler ultrasound must be con- ment of a testicular prosthesis.
firmed following the maneuver. – Delay performing this procedure, usually
– Other signs suggestive of successful man- for 6 months, until healing is complete and
ual detorsion include: inflammatory changes resolve.
• Resolution of the transverse lie of the – Perform the prosthetic placement through
testis to a longitudinal orientation an inguinal incision.
• Lower position of the testis in the • Recent studies show that exocrine and endo-
scrotum crine function is subnormal in men with a his-
• Return of normal arterial pulsations tory of unilateral torsion.
detected with a Doppler ultrasound • This is based on the following three theories
– Manual detorsion of the affected testicle is which explain the contralateral disease noted
not recommended if the duration of torsion in patients with testicular torsion:
is longer than 6 h. – Unrecognized repeated injury to both testes
– Following successful manual detorsion, – Preexisting pathologic condition predis-
elective bilateral orchidopexy is recom- posing to both abnormal spermatogenesis
mended, to prevent recurrent torsion and and torsion of the spermatic cord
protect the contralateral side from torsion. – Induction of pathologic changes in the con-
– The success rate of manual detorsion is tralateral testis by retention of the injured
variable ranging from 26.5 % to more than testis (autoimmune)
80 %. – To explain the decreased fertility observed
– It must be remembered that nonoperative in unilateral torsion of the spermatic cord,
manual detorsion is not a substitute for sur- several theories suggest an autoimmune
gical exploration. mechanism. This hypothesis is based upon
– If manual detorsion is successful (con- the following:
firmed by color Doppler ultrasound in a • Knowledge of the blood-testis barrier,
patient with complete resolution of symp- which isolates the luminal compartment
toms), the patient should undergo defini- of the seminiferous tubule
tive surgical fixation of the testes before • Inducing experimental allergic orchitis
leaving the hospital, so that the operation • The contralateral testicular disease
can be performed as an urgent rather than resembles sympathetic ophthalmia, a
emergency procedure. cell-mediated immune response
• The placement of a testicular prosthesis is

usually delayed for 6 months, until healing is
complete and inflammatory changes resolve.
26.9 Intra-uterine Torsion

of Testes
26.9.1 Introduction
• Intra-uterine torsion of testes is an extravagi-

nal torsion (Figs. 26.12, 26.13, and 26.14).
• It is very rare and seen most commonly in
neonates.
• It constitutes approximately 5 % of all testicu-
lar torsions.
• The majority of extravaginal torsions occur
prenatally (70 %) and 30 % occur postnatally.
• The timing of post-natal torsion is variable.
There are cases seen immediately after birth Figs. 26.12 and 26.13 Clinical intraoperative photo-
graphs showing intrauterine testicular torsion. Note the
but the majority of post-natal torsions occur site of torsion which is extravaginal
within the first 2 weeks.
• Extravaginal torsion is known to be associated
with high birth weight.
• Bilateral perinatal torsion is thought to be
rare, but an increase in the number of case
reports has been observed.
26.9.2 Etiology of Extravaginal

Torsion
• The exact etiology of intrauterine testicular

torsion is not known
• It is proposed that intrauterine testicular tor-
Figs. 26.14 Clinical intraoperative photograph showing a
sion occurs because the tunica vaginalis is not completely gangrenous left testis following intrauterine tor-
yet secured to the gubernaculum and, there- sion. The right testi was also necrotic (Bilateral torsion)
fore, the spermatic cord, as well as the tunica
vaginalis, undergo torsion as a unit.
• In neonates, the testes frequently has not yet 26.9.3 Clinical Features
fully descended into the scrotum, where it
becomes attached within the tunica vaginalis. • Commonly, these patients present immedi-
This mobility of the testicle predisposes it to ately after birth.
extravaginal torsion. • Prenatal, the usual presentation of extravaginal
• Extravaginal torsion is not like the commonly torsion is (Figs. 26.15, 26.16, 26.17, and 26.18):
seen intravaginal torsion is not associated – A hard
with the bell clapper deformity. – Nontender testis
26.9 Intra-uterine Torsion of Testes 563
Figs. 26.15, 26.16, 26.17, and 26.18 Clinical intraoperative photographs showing intrauterine torsion of testes. Note
the frankly necrotic testes
– That is fixed to the overlying scrotal skin – In an otherwise asymptomatic healthy

– Which is discolored newborn male
• It is thought that unilateral absence of the tes- – The scrotal skin characteristically fixes to
tis with blind-ending vessels is an indication the necrotic gonad
of early in utero testicular torsion as hemosid- – The scrotal skin is often discolored and the
erin is often found in the distal section of the affected side often appear darker than the
spermatic cord. contralateral side
• Acute scrotal swelling and tenderness without
fixation to the scrotal wall, may represent a post-
natal torsion with some hope of subsequent tes- 26.9.4 Treatment
ticular salvage with surgical exploration.
• Prenatal testicular torsion manifests as • The treatment of neonatal torsion is still con-
(Figs. 26.19, 26.20, 26.21, 26.22, 26.23, troversial (Figs. 26.27, 26.28, 26.29, and
26.24, 26.25, and 26.26): 26.30).
– A firm, hard, scrotal mass – Some advocate elective exploration and
– It does not trans illuminate contralateral orchidopexy because bilateral
Figs. 26.19, 26.20, and 26.21 Clinical photographs of three newborns with testicular torsion. Note the discoloration
of the scrotum. Note also the associated undescended right testis in the third patient
(synchronous or asynchronous) neonatal

testicular torsion has been described.
– If the testis is necrotic, an orchiectomy
and contralateral orchidopexy is
performed.
– Retention of a necrotic testis may exacer-
bate the potential for subfertility, presum-
ably because of development of an
autoimmune phenomenon. This however
is not fully supported.
– To prevent subsequent torsion on the
other side contralateral orchiopexy is
always performed.
– There are others who advocate emergency
exploration.
• The argument in favor of this is that
the timing of testicular torsion is not
exactly known and although the chance
Figs. 26.22 and 26.23 Clinical intraoperative photo-
graphs showing intrauterine torsion of testis. Note the site of saving the testis is small, this is
of twist which is extravaginal worth doing.
26.10 Torsion of the Testicular or Epididymal Appendage 565
Figs. 26.24, 26.25, and 26.26 Clinical intraoperative photographs showing frankly necrotic testes following intra-
uterine torsion
• Add to this the fact that these patients 26.10 Torsion of the Testicular
are usually healthy of good size and cur- or Epididymal Appendage
rently the anesthesia is safe.
• Many authors feel that these patients 26.10.1 Introduction
should be managed with early exploration
and if the testis is found necrotic, orchi- • Torsion of testicular appendices is one of the
dectomy and contralateral orchidopexy is most common causes of acute scrotum.
performed. If the testis is found viable, • It is considered the leading cause of acute
bilateral orchidopexy is performed. scrotum in children.
Figs. 26.27, 26.28, 26.29, and 26.30 Clinical intraop- cal exploration is important in these patients as the exact
erative photographs of four patients with intrauterine tor- timing of torsion is not known and in some of these
sion. The testes were found congested and dusky but patients, torsion may occur at the time of delivery or
viable. All underwent bilateral orchidopexy. Early surgi- shortly after

common testicular
appendages
VAS AND VESSELS
THE
EPIDIDYMAL
APPENDIX
THE APPENDIX
TESTIS
• This is considered the most common cause of • In those with acute scrotal pain, the incidence
acute scrotal pain in boys aged 7–14 years. of torsion of testicular appendage ranges from
• It can resemble testicular torsion but the onset 46–71 %.
of pain is more gradual. • Torsion of the testicular appendices is
• Systemic symptoms are rare. virtually a benign condition, but must be
• Localized tenderness occurs but only in the distinguished from testicular torsion
upper pole of the testis. (Fig. 26.31).
Fig. 26.32 An
intraoperative photograph
showing torsion of the
appendix testis in a child
NECROTIC
APPENDIX
TESTIS
• The appendix testis and epididymal appendix • The usual presentation is acute scrotal pain but
are commonly pedunculated and because of the onset is more gradual. This is important in
this are predisposed to torsion. distinguishing this from testicular torsion.
• Torsion of either appendage (The appendix • The pain is more localized to the upper pole of
testis and Epididymal appendix) produces the testis which is also tender.
pain similar to that experienced with testicular • The pain is usually not associated with sys-
torsion, but the onset is usually more gradual. temic symptoms, nausea, vomiting or urinary
symptoms.
• Localized tenderness occurs but only in the
26.10.2 Embryology upper pole of the testis.
• Usually, the scrotum appears normal but
• The appendix testis: sometimes there is an associated erythema
– This is a Müllerian duct remnant. and edema.
– It is present in 92 % of all testes. • The cremasteric reflex is usually intact.
– It is located at the superior pole of the testis in • Occasionally, a paratesticular nodule at the
the groove between the testis and epididymis. superior aspect of the testicle is present. This
– It is the most common appendage to is called the blue-dot sign which is present in
undergo torsion. only 20 % of cases (Fig. 26.32).
• The epididymal appendix: • This is the appendix of the testis which has
– This is a Wolffian duct remnant. become discolored and is noticeably blue
– The appendix epididymis is present in 23 % through the skin.
of testes.
– It is usually located on the head of the
epididymis. 26.10.4 Investigations
– It is the second common appendage to and Treatment
undergo torsion.
• Ultrasonography can be useful in distinguish-
26.10.3 Clinical Features ing torsion of a testis and torsion of an appen-
dix testis.
• The majority (80 %) of torsion of the testicular • Color Doppler ultrasonography is the imaging
or epididymal appendage occurs in boys aged modality of choice for evaluation of the acute
7–14 years (Mean age 10.6 years). scrotum.
• This usually shows normal blood flow to the 4. Blank BH, Goldsmith G, Schneider RE. Recognizing
a testicular emergency. Patient Care. 1997;31(13):
testis and sometimes an increase on the
117–35.
affected side due to inflammation. 5. Boettcher M, Bergholz R, Krebs TF, Wenke K,
• This is a self-limiting condition and most Aronson DC. Clinical predictors of testicular torsion
cases are treated conservatively. in children. Urology. 2012;79(3):670–4.
6. Brandt MT, Sheldon CA, Wacksman J, Matthews
• The treatment is conservative and the condi-
P. Prenatal testicular torsion: principles of manage-
tion usually resolves within 2–3 days. ment. J Urol Mar. 1992;147(3):670–2.
• Rarely surgery is indicated: 7. Coley BD. The acute pediatric scrotum. Ultrasound
– If it is difficult to differentiate from testicu- Clin. 2006;1:485–96.
8. Dajusta DG, Granberg CF, Villanueva C, Baker
lar torsion.
LA. Contemporary review of testicular torsion: new
– If the pain is severe and cannot be con- concepts, emerging technologies and potential thera-
trolled by analgesics. peutics. J Pediatr Urol. Oct 5 2012.
• The management includes: 9. Dogra V, Bhatt S. Acute painful scrotum. Radiol Clin
North Am. 2004;42(2):349–63.
– Bed rest and scrotal elevation.
10. Johnston BI, Wiener JS. Intermittent testicular tor-
– Nonsteroidal anti-inflammatory drugs and sion. BJU Int. 2005;95(7):933–4.
analgesics. 11. Lewis AG, Bukowski TP, Jarvis PD, et al. Evaluation
– Torsion of a testicular appendage may be of acute scrotum in the emergency department.
J Pediatr Surg. 1995;30(2):277–81. discussion 281–2.
misdiagnosed as epididymitis but if the uri-
12. Lopez RN, Beasley SW. Testicular torsion: potential
nalysis is normal, no antibiotic therapy is pitfalls in its diagnosis and management. J Paediatr
required. Child Health. 2012;48(2):E30–2.
– The inflammation usually resolves within a 13. Rabinowitz R, Hulbert Jr WC. Acute scrotal swelling.
Urol Clin North Am. 1995;22(1):101–5.
week.
14. Riaz-Ul-haq M, Abdelhamid Mahdi DE, Uthman
EE. Neonatal testicular torsion; a review article. Iran
J Pediatr. 2012;22(3):281–9.
15. Sharp VJ, Kieran K, Arlen AM. Testicular torsion:
Further Reading diagnosis, evaluation, and management. Am Fam
Physician. 2013;88(12):835–40.
1. Al-Salem AH. Intrauterine testicular torsion: a surgi- 16. Sun J, Liu GH, Zhao HT, Shi CR. Long-term influ-
cal emergency. J Pediatr Surg. 2007;42(11):1887–91. ence of prepubertal testicular torsion on spermatogen-
2. Baker LA, Sigman D, Mathews RI, et al. An analysis esis. Urol Int. 2006;77(3):275–8.
of clinical outcomes using color doppler testicular 17. Turgut AT, Bhatt S, Dogra VS. Acute painful scrotum.
ultrasound for testicular torsion. Pediatrics. Ultrasound Clin. 2008;3:93–107.
2000;105(3 Pt 1):604–7. 18. Yagil Y, Naroditsky I, Milhem J, Leiba R, Leiderman
3. Barada JH, Weingarten JL, Cromie WJ. Testicular sal- M, Badaan S, et al. Role of doppler ultrasonography
vage and age-related delay in the presentation of tes- in the triage of acute scrotum in the emergency depart-
ticular torsion. J Urol. 1989;142(3):746–8. ment. J Ultrasound Med. 2010;29(1):11–21.
Testicular Tumors in Children
27
27.1 Introduction • In the pediatric age group, the annual inci-

dence of testicular cancer is approximately
• Testicular tumors are relatively rare in the 1 in 100,000 male children per year.
pediatric age group. • Others reported the incidence of testicular
• They account for only 1–2 % of all Pediatric tumors in children to be only 1.6 per 1 million
Solid Tumors. children-years.
• Children represent only 2–5 % of all patients • Testicular tumors are rare in children com-
with testicular cancer. pared with testicular tumors occurring post-
• The exact incidence of testicular cancer is not pubertally or with other genitourinary tumors
known but it has been estimated at 5.5 cases in childhood such as Wilms tumor (Figs. 27.1
per 100,000 men per year. and 27.2).
• Others reported an incidence of testicular • The majority of testicular tumors occur in
cancer of 2.75–8 per 100,000 men per children <2 years of age.
year. • 75 % of testicular tumors occur before age
• Testicular cancer rates are lowest in Asian and 2.5 years.
African populations, at less than 1 case per • Benign Tumors Account for 38 % of all tes-
100,000 men per year. ticular tumors.
• Testicular cancer rates are highest in devel- • However, there is actually a bimodal age dis-
oped European countries at eight to nine cases tribution for testicular tumors with a large
per 100,000 men per year. peak in young adults and a much smaller peak
• Testicular tumors are more common in whites in the first 3 years of life.
with a white-to-black incidence ratio of approx- • This bimodal age distribution reflects more
imately 5:1. fundamental differences between prepubertal
• The highest rates of prevalence of testicular and postpubertal testicular tumors.
cancer is in Scandinavia, Germany, and New • These differences include the typical tumor
Zealand. histology in each group, the malignant poten-
• Testicular cancers are considered the most tial of tumors at different ages, and the molec-
common cancer in males aged 20–39 years. ular biological differences between
• The median age for diagnosis of testicular prepubertal and postpubertal tumors.
cancer has been reported at 33 years. • The most striking difference between prepu-
• Testicular cancer is rarely seen before the age bertal and postpubertal tumors is the incidence
of 15 years. distribution of different tumor types.

570 27 Testicular Tumors in Children
Figs. 27.1 and 27.2 Scrotal ultrasound and MRI showing left testicular tumor in a child. This proved to be a Leydig
cell tumor
• Teratoma is considered the most common type • Other studies reported cancer in contralateral
in children. testis in 20 % of cases.
• Undescended testes is a well-known risk of • Chromosomal Abnormalities (del(1p36)) are
testicular cancer. seen in 80 % of Yolk Sac Tumors
• Testicular cancer is two times to three times • Patients with Disorders of Sex Development
more common in boys undergoing prepubertal (DSD) have increased incidence of testicular
orchiopexy tumors.
• Postpubertal orchiopexy are two to six times • Hypovirilization and gonadal dysgenesis are
more likely to develop testicular cancer than at higher risk of developing testicular tumors.
the general population. • The presence of Y chromosome in gonadal
• The relative risk of testicular cancer increases dysgenesis increases the risk of testicular can-
with age at orchiopexy. cer to 10 % by age of 20.
• The relative risk of testicular cancer increases • Intratubular germ cell neoplasia has been
the higher the position of undescended noted in 6 % of children with DSD.
testes. • Germ cell testicular tumors are the most com-
• Others reported that 3.8 % of children with mon solid tumors in men aged 15–35 years.
abdominal undescended testes, abnormal
external genitalia, or abnormal karyotype
develop testicular cancer. Testicular Cancer is Most Common Among
• The relative risk of testicular cancer increases Men Aged 15–40 Years, but it Has Three
in those with bilateral cryptorchidism. Peaks Depending on the Type
• 74 % of malignancies in persistent cryptorchid • Infants – 4 years of age: Teratomas and
testes, are seminoma. yolk sac tumors.
• 63 % of malignancies in post orchiopexy • 25–40 years of age: Seminomas and
patients, are non-seminoma. nonseminomas.
• There is no increased risk for tumors in the • 60 of age: Spermatocytic seminomas.
contralateral normally descended testis
• The symptoms of testicular tumors may • Seminomas comprise approximately 50 % of

include one or more of the following: all germ cell tumors.
– Testicular swelling which may or may not • Seminomas are generally believed to arise
be painful from the germinal epithelium of the seminif-
– Sharp or a dull aching pain in the lower erous tubules because “seminoma cells” are
abdomen or scrotum morphologically similar to spermatogonia and
– Heaviness in the scrotum also because seminomas are frequently found
– Rarely, gynecomastia may develop from within the seminiferous tubules in early stages.
hormonal effects of β-hCG • Seminoma is confined to the testis in 85 % of
– Low back pain from tumor spread to the patients at presentation.
lymph nodes along the back • Unlike the nonseminomatous germ cell
– Shortness of breath and cough from meta- tumors, pure seminoma tends to remain local-
static spread to the lungs ized or tends to involve only lymph nodes.
• Pediatric prepubertal testicular tumors are • It initially spreads to draining lymph nodes
dramatically different from adult neoplasms. in the retroperitoneum and then spreads
• Germ-cell tumors account for only 60–77 % proximally to involve the lymphatics in the
of testicular tumors in children but account for mediastinum and supraclavicular lymph
95 % of testicular tumors in adults. nodes.
• Adult germ-cell tumors with malignant • Only rarely does pure seminoma spread hema-
potential, such as seminoma and embryonal togenously to involve lung parenchyma, bone,
carcinoma, are rarely seen in prepubertal liver, or brain.
patients. • Epidermoid cysts are generally considered a
• Testicular tumors are generally classified by monodermal form of teratoma.
the putative cell of origin. • Gonadoblastomas, which occur almost exclu-
• Testicular tumors are broadly classified into sively in the setting of disorders of sexual
two main groups; development, contain both germ cell and stro-
– Germ-cell tumors mal elements.
– Stromal tumors • Mixed germ cell tumors which contain two or
• In both children and adults, the vast majority more histological types are particularly com-
of testicular tumors arise from germ cells. mon in adolescents and adults whereas prepu-
• Seminoma, the most common germ cell tumor bertal germ cell tumors are virtually always of
is considered a postpubertal tumor, although it a single histological type.
has been reported in patients as young as
8 years.
Stromal Tumors
• Leydig cell tumor
Germ Cell Tumors Account for 95 % of
• Sertoli cell tumor
Testicular Tumors in Adult but Only 60–77 %
• Juvenile granulosa cell tumor
in Children and Include
• Seminomas
• Teratomas
• Embryonal carcinoma • Testicular tumors may also be classified based
• Choriocarcinomas on their clinical behavior as benign or
• Yolk sac tumors malignant.
• Mixed tumors. • Seminoma, embryonal carcinoma, choriocar-
cinoma and yolk sac tumors are malignant.
• Teratomas, which are uniformly benign in • ITGCN is also generally absent in prepubertal
children, are often malignant in adults. testicles harboring a teratoma, while 88 % of
• Histologically, teratoma is often pure with testes removed for adult teratoma contain
diploid DNA content containing all three areas of ITGCN.
embryological germ layers (ectoderm, meso- • These differences in histological distribution
derm, and endoderm). and clinical behavior have led to a divergence
• The most common germ-cell tumors are tera- in the management strategies for prepubertal
tomas and yolk-sac tumors, which account for and postpubertal tumors.
about 62 % and 26 % of testicular tumors, • In children, a testis-sparing approach is
respectively. becoming more common given the high
• Some series report that teratomas, which most incidence of benign tumors in this
believe are vastly underreported because of population.
their benign nature, may account for almost • When a malignant tumor is identified, orchi-
50 % of prepubertal testicular tumors. ectomy and observation with very selective
• However, in tumor registries, yolk-sac tumors use of chemotherapy has become the standard
are more common than teratomas, perhaps approach; retroperitoneal lymph node dissec-
reflecting a reporting bias. tion (RPLND) and radiation therapy play a
• Prepubertal teratomas account for less than very limited role.
30 % of testicular germ-cell tumors in children • Gonadal stromal tumors are significantly less
and are uniformly benign. common than germ-cell tumors (i.e. tumors of
• Most stromal tumors are benign, though occa- non–germ-cell origin) and primarily include
sionally malignant behavior is seen, particu- juvenile granulosa-cell tumors, Leydig-cell
larly in older patients. tumors, and Sertoli-cell tumors.
• The large majority of testicular tumors in ado- • The vast majority (85 %) of yolk-sac tumors in
lescents and adults are malignant germ cell children present as clinical stage I disease,
tumors – most commonly mixed germ cell compared with only 35 % in adults.
tumors with pure seminomas occurring in • An intratesticular lesion should be considered
older men. a malignancy unless proven otherwise.
• In contrast, the most common germ cell tumor • Scrotal sonography localizes the lesion and
in children is a benign teratoma. distinguishes a solid from a cystic mass.
• The most common malignant tumor in chil- • It can be extremely helpful in detecting small
dren is a yolk sac tumor, which is very rare in lesions within the testis, but its findings are
its pure form in post-pubertal patients. not specific and by itself cannot exclude
• Overall, approximately 75 % of testis tumors malignancy.
in prepubertal patients are benign. • A biopsy should not be performed, as it raises
• Molecular biological and histological studies the risk of spreading cancer cells into the
further support the distinct nature of prepuber- scrotum.
tal and postpubertal testis tumors. • Inguinal orchiectomy is the preferred method
• For example, chromosome 12 abnormalities to treat testicular cancer.
are seen in nearly all adult malignant germ • The lymphatic system of the scrotum is linked
cell tumors, but are not seen in prepubertal to the lower extremities, while the testicle
yolk sac tumors which display abnormalities lymphatics drain to the retroperitoneum.
in other chromosomes. • A transscrotal biopsy or orchiectomy will
• Intratubular germ cell neoplasia (ITGCN) potentially lead to spread of cancer cells in the
which is frequently seen in the testicles of scrotum and subsequent spread to the inguinal
men with malignant germ cell tumors, does nodes and further, while in an inguinal orchi-
not occur in the setting of prepubertal yolk sac ectomy only the retroperitoneal route of
tumor. spread exists.
27.2 Classification of Testicular Tumors 573
• Alpha-fetoprotein (AFP) can be used as a reli- – Treatment options for potentially malignant
able tumor marker because levels are increased tumors include surveillance, chemotherapy,
in more than 90 % of yolk-sac tumors. retroperitoneal lymph node dissection
Therefore, patients can be safely managed (RPLND), and radiation therapy.
with observation after orchiectomy followed – Virtually all germ cell tumors are sensitive
by chemotherapy for recurrent tumors. to platinum-based multiagent chemother-
• Retroperitoneal lymph node dissection is apy which plays a major role in their
reserved for children with persistent retroperi- management.
toneal lymphadenopathy or increased serum – RPLND plays an important staging and
tumor markers after orchiectomy and therapeutic role for mixed germ cell tumors
chemotherapy. in adolescents, but is rarely employed in
• Testis-sparing surgery with frozen section is a cases of prepubertal yolk sac tumor.
reasonable consideration for this and other – Radiation therapy is primarily used in
benign prepubertal tumors. No follow-up is treating seminoma – a very rare tumor in
recommended for prepubertal teratomas, the pediatric population. The specific adju-
whereas postpubertal patients should be moni- vant therapy for a given patient is depen-
tored into adulthood. dent on tumor histology and stage.
• Tumor excision without orchiectomy is par- • Testicular cancer has one of the highest cure
ticularly attractive in prepubertal patients rates of all cancers:
because most tumors are benign in this – If the cancer did not spread outside the tes-
population. ticle, the 5-year survival rate is 99 %.
• An elevated AFP level in a child over 1 year of – If the cancer has grown into nearby struc-
age virtually always reflects the presence of a tures or has spread to nearby lymph nodes,
yolk sac tumor and precludes a testis-sparing the 5-year survival rate is 96 %.
approach. – If the tumor has spread to organs or lymph
• For a testis-sparing approach, the testis is nodes away from the tumor, the 5-year sur-
delivered into the inguinal incision (the cord vival rate is around 74 %.
having been occluded with a non-crushing
clamp or vessel loop), the field is draped off
with towels and the tunica vaginalis is opened. 27.2 Classification of Testicular
The tumor is excised or enucleated and sent Tumors
for frozen section. If a benign histology is
confirmed, then the testicular defect is closed • The most striking difference between prepu-
with absorbable suture and the testis is bertal and postpubertal tumors is the incidence
returned to the scrotum. If a malignancy is distribution of different tumor types.
detected, or the frozen section is nondiagnos- • Testicular tumors are generally classified
tic, then an orchiectomy is performed. Reports according to the cells of origin.
from small series suggest that this approach is • Germ cell tumors include:
safe and is effective in preserving testicular – Seminoma
tissue. – Embryonal carcinoma
• The lesions successfully treated with tumor – Choriocarcinoma
enucleation (Testis-sparing surgery) included – Yolk sac tumor
teratomas, epidermoid cysts, Sertoli cell – Teratoma. Epidermoid cysts are generally
tumors, and Leydig cell tumors. considered a monodermal form of teratoma.
• Adjuvant therapy: • Stromal tumors include:
– Following excision of the primary tumor, – Leydig cell tumor
universally benign tumors require no fur- – Sertoli cell tumor
ther evaluation or treatment. – Juvenile granulosa cell tumor.
• Gonadoblastomas, which occur almost exclu-

sively in those with disorders of sexual devel- Classification of Testicular Tumors
opment, contain both germ cell and stromal • Testicular tumors are divided into two
elements. types:
• Mixed germ cell tumors which contain two or – Primary testicular tumors
more histological types are particularly com- – Secondary testicular tumors
mon in adolescents and adults whereas • Primary testicular tumors:
prepubertal germ cell tumors are virtually – Germ cell tumors (95 %)
always of a single histological type. • Seminomas (45 %)
• Testicular tumors may also be classified based • Nonseminomas (50 %)
on their clinical behavior as benign or – Mixed germ cell tumors (40 %)
malignant. – Teratoma and teratocarcinomas
• Malignant testicular tumors include: (30 %)
– Seminoma – Embryonal cell tumor (20 %)
– Embryonal carcinoma – Choriocarcinoma (1 %)
– Choriocarcinoma – Yolk sac tumors (endodermal
– Yolk sac tumors sinus tumors)
– Teratomas are universally benign in prepu- – Non-germ cell tumors (5 %)
bertal patients, but may behave in a malig- • Stromal Leydig cell tumors
nant fashion in adolescents and adults. • Sertoli cell tumors
• Benign testicular tumors include: • Gonadoblastoma
– Most stromal tumors are benign, though • Mixed Germ cell tumors
occasionally malignant behavior is seen, • Secondary testicular tumors:
particularly in older patients. – Lymphoma, leukemia, and mela-
– The large majority of testicular tumors in noma are the most common malig-
adolescents and adults are malignant germ nancies that metastasize to the
cell tumors – most commonly mixed germ testicle.
cell tumors with pure seminomas occurring
in older men.
– In contrast, the most common germ cell
tumor in children is a benign teratoma. • Testicular tumors are also classified into:
– The most common malignant tumor in – Primary testicular tumors
children is a yolk sac tumor, which is very – Secondary or metastatic tumors
rare in its pure form in post-pubertal • The World Health Organization classification
patients. system for testicular tumors:
– Overall, approximately 75 % of testicu- • Germ cell tumors
lar tumors in prepubertal patients are – Precursor lesions
benign. • Intratubular germ cell neoplasia
• Although testicular cancer can be derived – Unclassified type (carcinoma in situ)
from any cell type found in the testicles, more – Specified types
than 95 % of testicular cancers are germ cell – Tumors of one histologic type (pure forms)
tumors. • Seminoma
• Most of the remaining 5 % are sex cord- – Variant – Seminoma with syncytio-
gonadal stromal tumors derived from Leydig trophoblastic cells
cells or Sertoli cells. • Spermatocytic seminoma
• Correct diagnosis is necessary to ensure the – Variant – spermatocytic seminoma
most effective and appropriate treatment. with sarcoma
27.2 Classification of Testicular Tumors 575
• Embryonal carcinoma • Miscellaneous tumors of the testis

• Yolk sac tumor – Carcinoid
• Trophoblastic tumors – Tumors of ovarian epithelial types
– Choriocarcinoma • Serous tumour of borderline
• Variant – monophasic malignancy
choriocarcinoma • Serous carcinoma
– Placental site trophoblastic tumor • Well differentiated endometrioid tumour
– Cystic trophoblastic tumor • Mucinous cystadenoma
• Teratoma • Mucinous cystadenocarcinoma
– Variant – Dermoid cyst • Brenner tumour
– Variant – Epidermoid cyst – Nephroblastoma
– Variant – Monodermal teratoma – Paraganglioma
(Carcinoid, Primitive neuroectoder- • Haematopoietic tumors
mal tumor (PNET), Nephroblastoma- • Tumors of collecting ducts and rete
like tumor, others). – Adenoma
– Variant – Teratomic with somatic-type – Carcinoma
malignancy • Tumors of the paratesticular structures
– Tumors of more than one histologic type – Adenomatoid tumour
(mixed forms) – Malignant and Benign Mesothelioma
• Embryonal carcinoma and teratoma – Adenocarcinoma of the epididymis
• Teratoma and seminoma – Papillary cystadenoma of the epididymis
• Choriocarcinoma and teratoma and – Melanotic neuroectodermal tumour
embryonal carcinoma – Desmoplastic small round cell tumour
• Others • Mesenchymal tumors of the spermatic cord
• Sex cord/Gonadal stromal tumors and testicular adnexae
– Leydig cell tumor – Lipoma
– Sertoli cell tumor – Liposarcoma
• Lipid rich variant – Rhabdomyosarcoma
• Scleriosing variant – Aggressive angiomyxoma
• Large cell calcifying variant – Angiomyofibroblastoma-like tumour (see
• Intratubular sertoli cell neoplasia in Myxoma)
Peutz-Jeghers syndrome – Fibromatosis
– Granulosa cell tumour – Fibroma
• Adult type – Solitary fibrous tumour
• Juvenile type – Others
– Thecoma Fibroma Group • Secondary tumors of the testis
– Sex cord/gonadal stromal tumor – incom- • The most common type of testicular tumor in
pletely differentiated children is the germ cell tumors.
– Sex cord/gonadal stromal tumour – mixed • Endodermal sinus tumor (yolk sac tumor) and
types teratomas are the most common germ cell
• Thecoma tumors among all testis tumors in children.
• Fibroma • These tumors present with a malignant behav-
• Mixed Germ Cell and Sex Cord/Gonadal ior sometimes. These tumors spread to the
Stromal Tumors lung, retroperitoneal lymph nodes, bone, or
– Gonadoblastoma the central nervous system.
– Germ cell-sex cord/gonadal stromal • The most common malignant tumor is usually
tumour, unclassified the endodermal sinus tumor in children.
• Teratomas are the most common benign

tumors in children. Histologic Classification of Seminomas
• Recent reports found that teratomas were • Classic seminomas (85 %)
more common than endodermal sinus tumors • Anaplastic seminoma (10 %)
in children. • Spermatocytic seminoma (5 %)
• The gonadal stromal tumors are usually
benign, there has been the very rare case of
malignant gonadal stromal tumor. • Classic seminomas (85 %):
• Juvenile granulosa cell tumors are the most – They demonstrate a monotonous sheet of
common tumors among neonatal tumors. large cells with abundant cytoplasm and
These tumors are benign. round hyperchromatic nuclei with promi-
nent nucleoli.
– A lymphocytic infiltrate or granulomatous
27.3 Histologic Classification reaction with giant cells or both is fre-
of Seminomas quently present.
– Trophoblastic giant cells capable of pro-
ducing hCG are present in 15–20 % of
Classification of Testicular Tumors tumors.
• Germ Cell Tumors – Mitoses are infrequent.
– Seminomas • Anaplastic seminoma (10 %):
– Teratomas – This is an older term used to describe semi-
– Embryonal carcinoma nomas with three or more mitotic figures
– Choriocarcinomas per high-power field.
– Yolk sac tumors (Endodermal sınus – This finding has no clinical or prognostic
tumor) significance because the response of ana-
– Mixed germ cell tumors. plastic seminomas to standard therapy is
• Gonadal Stromal Tumors equivalent to that of classic seminomas.
– Leyding cell • Spermatocytic seminoma (5 %):
– Sertoli cell – This is a rare histologic variant that is not
– Juvenile granuloza gell associated with carcinoma in situ.
• Mixed form – These well-differentiated tumors usually
• Gonadoblastoma contain cells resembling secondary sper-
• Tumors of Supporting Tissues matids or spermatocytes.
– Fibroma – Spermatocytic seminomas rarely metasta-
– Leimiyoma size, and they occur almost exclusively in
– Hemangioma elderly men.
• Lymphomas and Leukemias – The only recommended treatment is
• Tumor like Lesions orchiectomy.
• Epidermoid cysts
• Hyperplastic nodule secondary to con-
genital adrenal hyperplasia 27.4 Etiology of Testicular Tumors
• Secondary Tumors
• The exact etiology of testicular cancer is not
clearly known.
• Grossly, seminomas are pale gray–to-yellow • There is a dramatic increase in the incidence
nodules that are uniform or slightly lobulated. rate of testicular cancer in developed countries
• Pure seminomas are subdivided into three sub- and the reason for this is not known.
types based on histopathologic characteristics:
27.4 Etiology of Testicular Tumors 577
• Most testicular tumors occur sporadically, but suggests that an inherent developmental
familial cases have been observed and some defect is responsible for both the unde-
cases occur because of a predisposing history. scended testes and the tumor development.
– It has been found that the risk of develop-
ing testicular cancer in patients with
Risk Factors for Testicular Cancer undescended testes is directly related to the
• Cryptoorchidism degree of maldescent.
• Testicular microlithiasis • The risk is 1 in 20 if the testis is
• Disorders of sexual development intra-abdominal.
• Familial predisposition • The risk is 1 in 80 if it is within the
• Other associations: inguinal canal.
– Iguinal hernias – Whether early orchidopexy can amelio-
– Klinefelter syndrome rate that risk is unclear. Currently, it is
– Mumps orchitis believed that orchiopexy performed before
– Hypospadias and hydrocele puberty reduces the risk of germ cell
– Chromosome 12 abnormalities tumors and improves the ability to observe
– Prior testicular cancer increases the the testis.
risk on the contralateral testis – The increased risk of germ cell tumors is
– Human immunodeficiency virus reflected in the finding of carcinoma in situ
(HIV) infection in 2–4 % of men with a history of
– History of testicular trauma cryptorchidism.
– Immunosuppression after organ • Testicular microlithiasis:
transplant – Testicular microlithiasis refers to the pres-
– Prior vasectomy ence of microcalcifications, usually dif-
– The use of cannabis and marijuana fuse, within the parenchyma of the testis on
– An association with prenatal expo- ultrasound.
sure to diethylstilbestrol (DES) has – Testicular microlithiasis is defined as ≥5 or
been postulated but not demonstrated more microcalcifications within a testicle.
– Teticular microlithiasis is found incidentally
in approximately 2 % of boys and men
undergoing testicular ultrasound evaluation.
• A major risk factor for the development of tes- – This has been identified as a possible risk
tis cancer is cryptorchidism (undescended factor for the development of testicular
testicles). cancer but the reason for this association is
– The risk of testicular cancer in men with a not clear.
history of undescended testis has been esti- – The association with testicular malignan-
mated at 10 to 40-fold greater than the gen- cies was suggested by the finding that
eral population. approximately 25 % of adult testes harbor-
– More recent studies have found the risk to ing cancer are found to have testicular
be fivefold greater than that of the general microlithiasis.
population. • Disorders of sexual development (Figs. 27.3,
– The life-time risk for testicular cancer in 27.4, 27.5, 27.6, 27.7, 27.8, 27.9, and 27.10):
those with undescended testis is 1–2 %. – Disorders of sexual development are a very
– 7–10 % of testis tumors occur in associa- significant risk for the development of
tion with cryptorchidism. gonadal tumors.
– 25 % of the cancers found in association – Some disorders, such as complete andro-
with cryptorchidism occur in the contralat- gen insensitivity syndrome, have an
eral, normally descended testis. This increased risk of testicular cancer.
Figs. 27.3, 27.4, 27.5, 27.6, and 27.7 Clinical intraop- phenotypic female external genitalia. These patients usu-
erative photographs showing patients with testicular femi- ally have intraabdominal testes which are at increased risk
nization syndrome. These are genotypically males with of malignant transformation and must be removed
– There is an increased risk in those with occur, dysgerminoma is the most common
dysgenetic or streak gonads. histological type. .
– This risk seems to exist almost exclusively – While most cases of malignancy occur
in patients with Y chromatin. after puberty, there have been case reports
– Patients with pure gonadal dysgenesis and in children as well.
Y chromatin as well as the “streak” gonad – Prophylactic removal of dysgenetic
of patients with mixed gonadal dysgenesis gonads should be undertaken early in life
are at a 15–30 % risk for tumor to avoid malignant transformation in these
development. patients.
– The tumors arising in those with gonadal • Other risk factors include:
dysgenesis are usually gonadoblastomas. – Inguinal hernias
– While gonadoblastomas are benign, they – Klinefelter syndrome
are prone to the development of malignant – Mumps orchitis
degeneration and when malignancies – Hypospadias and hydrocele
VAS
FALLOPIAN TUBE
VAS
OVOTESTES
OVOTESTES
Figs. 27.8, 27.9, and 27.10 Clinical intraoperative pho- lar part of an ovotestis is likely to be dysgenetic with a risk
tographs of a patient with ovotesticular DSD. Note the of developing dysgerminomas, seminomas, gonadoblas-
presence of an ovotestis on this side. The testis or testicu- tomas, and yolk sac carcinomas
– Chromosome 12 abnormalities are seen in 27.5 Clinical Features

nearly all adult malignant germ cell tumors,
but are not seen in prepubertal yolk sac tumors. • The incidence of pediatric testicular tumors
– Prior testicular cancer is a major risk factor for peaks in children aged 2–4 years.
a contralateral malignancy. The cumulative • Most yolk-sac tumors occur in children
risk 25 years after original diagnosis is 3.6 % younger than 2 years.
for patients with seminoma. • About 85 % of children with testicular tumors
– Human immunodeficiency virus (HIV) present with painless scrotal swelling.
infection • A few present with a hydrocele, scrotal pain,
– History of testicular trauma or a history of trauma, any of which probably
– Immunosuppression after organ transplant alerts the child to the presence of a painless
– Prior vasectomy and enlarged testicle.
– The higher rates of testicular cancer in • 10 % may give a history of hernia or
western nations have been linked to use of hydrocele
cannabis. Long term use of cannabis and • 15–50 % have hydrocele on physical exam
marijuana is linked to an increased risk for • Rarely, they may present with acute abdomi-
testicular cancer. nal pain
• The majority of testis tumors present as a pal- 27.6 Staging

pable testicular mass.
• This can be detected by the patient, a parent, or • In the Children’s Oncology Group staging
by a physician on routine physical examination. system:
• Occasionally the patients present with a • Stage I:
hydrocele. – Patients with locally confined disease, neg-
• About 10–25 % of patients with a malignant ative radiographic studies, and the expected
tumors present with a hydrocele. decline in tumor markers post-operatively.
• Therefore, if a child presents with a hydrocele • Stage II:
that clearly obscures physical examination of – Patients with microscopically positive mar-
the testis, an ultrasound should be done to gins in the scrotum or spermatic cord and/
exclude an associated tumor. or with persistently elevated tumor markers
• Rarely, patients may present with testicular after orchiectomy. Patients who underwent
pain. transcrotal biopsy prior to orchiectomy at a
• Signs related to metastatic disease are uncom- separate setting are also considered stage 2.
mon in children as the most common sites – • Stage III:
the retroperitoneum and lungs – rarely result – Patients with retroperitoneal lymphadenopathy.
in physical findings. • Stage IV:
• The most common presenting symptom in a – Patients with distant metastases (most
patient with seminoma is a painless testicular commonly in the lungs).
mass. Other symptoms can include testicular • Adolescents with germ cell tumors are gener-
pain (45 %) or heaviness. ally staged as adults utilizing the TNM system
• A history of previous testicular trauma is com- of the American Joint Committee on Cancer
mon. The trauma typically draws the patient’s and the International Union Against Cancer.
attention to the mass and not a cause.
• Seminoma that has spread to retroperitoneal
lymph nodes can cause back pain or abdomi- The Children’s Oncology Group Staging
nal discomfort. System
• Widely disseminated metastatic disease to • Stage I: Patients with locally confined
lungs, liver, bone, or brain is rare but may pro- disease, negative radiographic studies,
duce systemic symptoms. and the expected decline in tumor mark-
• A history of cryptorchidism or other genitouri- ers post-operatively.
nary anomalies can be elicited in some patients. • Stage II:
• Once a testis tumor is suspected, a thorough – Patients with microscopically positive
physical examination is undertaken. margins in the scrotum or spermatic
• Physical examination usually reveals a pain- cord and/or with persistently elevated
less scrotal swelling with a hard mass or asso- tumor markers after orchiectomy.
ciated hydrocele. – Patients who underwent transcrotal
• Some hormonally active tumors may appear biopsy prior to orchiectomy at a sep-
in association with precocious puberty or arate setting.
gynecomastia. • Stage III: Patients with retroperitoneal
• A hard mass may be palpable on physical lymphadenopathy.
examination. However, normal physical find- • Stage IV: Patients with distant metasta-
ings are not sufficient to exclude a tumor. ses (most commonly in the lungs)
• In most cases the general examination will be
normal.
• But occasionally signs of androgenization or • Testicular seminoma is staged according to
other physical findings will be present suggest- the American Joint Committee on Cancer
ing a particular tumor type or advanced disease. (AJCC) 2010 staging guidelines.
27.6 Staging 581
• This is a TNM staging system comprising • N2 – Metastasis with lymph node(s) larger
separate categorizations for the primary than 2 cm but not larger than 5 cm in greatest
tumor, regional lymph nodes, distant metasta- dimension, or multiple lymph nodes, any one
ses, and serum tumor markers. mass larger than 2 cm, but not more than 5 cm,
• These four categories are used to determine in greatest dimension
the stage of the patient’s disease. • N3 – Metastasis with lymph node(s) larger
• Modern treatment decisions are based, in part, than 5 cm in greatest dimension
on the subdivisions of this staging system. • Distant metastatic staging
• Primary tumor staging – M0 – No distant metastases
– Tis – Intratubular germ cell neoplasia (car- – M1a – Nonregional nodal or pulmonary
cinoma in situ) metastasis
– T1 – Tumor limited to testis/epididymis – M1b – Distant metastases other than M1a
without vascular or lymphatic invasion; • Serum tumor marker staging
tumor may invade into the tunica albuginea – S0 – Marker studies within normal limits
but not the tunica vaginalis – S1 – LDH level less than 1.5 times the ref-
– T2 – Tumor limited to testis/epididymis erence range, beta-hCG level less than
with vascular or lymphatic invasion or 5000 mIU/mL, and AFP level less than
tumor extending through tunica albuginea 1000 ng/mL
with involvement of the tunica vaginalis – S2 – LDH level 1.5–10 times the reference
– T3 – Tumor invading spermatic cord with range, beta-hCG level 5000–50,000 mIU/
or without vascular/lymphatic invasion mL, or AFP level 1000–10,000 ng/mL
– T4 – Tumor invading scrotum with or with- – S3 – LDH level more than ten times the ref-
out vascular/lymphatic invasion erence range, beta-hCG level more than
50,000 mIU/mL, or AFP level more than
10,000 ng/mL
The Intergroup Staging System for
Testicular Germ Cell Tumors
• Stage I: Tumor limited to the testis and
Children’s Oncology Group Staging System
completely resected (85 % of children
for Yolk Sac Tumors
<4 years present with stage I disease,
• Stage I:
whereas only 35 % of adults with testic-
– Limited to testis
ular tumors present with stage I)
– Completely resected by high ingui-
• Stage II: Tumor removed by transscrotal
nal orchiectomy
orchiectomy, involvement of scrotum or
– Tumor markers negative
spermatic cord, persistently elevated
– Unknown tumor markers at diagnosis
tumor markers.
– Need negative ipsilateral retroperito-
• Stage III: Retroperitoneal lymph node
neal lymph node biopsy if >2 cm on CT
involvement (≤2 cm, no visceral or
• Stage II:
extra-abdominal involvement)
– Microscopic residual disease
• Stage IV: Distant metastases
– Tumor markers remain elevated
– Tumor rupture or scrotal biopsy prior
to complete orchiectomy
27.6.1 Regional Lymph Node Staging • Stage III:
– Retroperitoneal lymph node
• N0 – No regional lymph node metastases involve987`ment
• N1 – Metastasis with lymph node(s) 2 cm or – (>4 cm on CT)
less in greatest dimension or multiple lymph – RPLN <4 cm, but >2 cm need biopsy
nodes, none more than 2 cm in greatest • Stage IV: Distant Metastasis
dimension
• Stage grouping: – Elevated AFP levels are rare in pure semi-

– Stage IA – T1 N0 M0 S0 nomas and indicate that nonseminomatous
– Stage IB – T2, 3, 4 N0 M0 S0 elements are also present (i.e., mixed
– Stage IS – Any T N0 M0 S1, 2, 3 tumor).
– Stage IIA – Any T N1 M0 S0, 1 – AFP is elaborated by 90 % of yolk sac
– Stage IIB – Any T N2 M0 S0, 1 tumors in children.
– Stage IIC – Any T N3 M0 S0, 1 – It is important to note that serum AFP lev-
– Stage IIIA – Any T Any N M1a S0, 1 els can normally be as high as 50,000 ng/
– Stage IIIB – Any T Any N M0, 1a S2 mL in the newborn dropping to approxi-
– Stage IIIC – Any T Any N M1a, 1b S3 mately 300 ng/mL by 2 months of age.
AFP levels do not achieve “normal” values
until nearly 1 year of age.
27.7 Investigations – Therefore, while an elevated AFP in a child
over 1 year old with a testis tumor almost
• CBC and differential. always reflects the presence of a yolk sac
• Liver function tests, electrolytes, BUN and tumor, an “elevated” level in infants can
creatinine. occur in the setting of a benign tumor.
• A chest x-ray or chest CT will identify pulmo- – The post-operative value of tumor markers
nary metastases. is also important.
• 20 % of yolk-sac tumors may present with – Tumor marker serum levels should fall at a
metastases to the lung. predictable rate based on the biological
• Measurements of alpha-fetoprotein (AFP), half-life of each marker (approximately
human chorionic gonadotropin (beta-hCG), 5 days for AFP and 48 h for HCG).
and lactate dehydrogenase (LDH) are impor- – Failure of the markers to decline at the
tant in the management of patients with tes- expected rate reflects the likely persistence
ticular tumors such as seminomas. of residual tumor.
• Tumor marker levels are used to assess – Persistently elevated AFP levels after
response to treatment and to predict the likeli- surgery suggest tumor metastases or
hood of complete remission. recurrence.
• Lactate dehydrogenase: The LDH level is an – Liver dysfunction can also cause false-
independent prognostic factor in patients with positive elevations of AFP levels.
germ cell tumors (including seminoma). It is – Beta-hCG is a glycoprotein typically pro-
thought to reflect tumor burden. duced by the placenta.
• Tumor markers: – Elevations in beta-hCG levels are found in
– These are important in the evaluation of the serum of approximately 15 % of
testis tumors in children and adolescents. patients with seminoma.
– Both human chorionic gonadotropin – The half-life of beta-hCG is approximately
(HCG) and alpha-fetoprotein (AFP) are 22 h.
important tumor markers. – Serum testosterone levels may be elevated
– Yolk sac tumors do not elaborate HCG, and in Leydig-cell tumors.
AFP is the only important tumor marker in – Gonadoblastoma may elevate levels of
prepubertal patients. beta-HCG.
– AFP is a glycoprotein typically associated • Scrotal, abdominal and pelvic ultrasound
with the human fetus. AFP is found in non- (Figs. 27.11 and 27.12):
seminomatous germ cell tumors, as well as – Imaging of the primary tumor almost always
in hepatocellular carcinomas, cirrhosis, begins with ultrasonography.
hepatitis, and pregnancy. – Ultrasound distinguishes testicular from
– The half-life of AFP is approximately 5 days. extratesticular masses and the ultrasono-
27.8 Treatment 583
Figs. 27.11 and 27.12 Scrotal ultrasound and MRI showing left testicular tumor. Histological evaluation showed this
to be Leydig cell tumor
graphic appearance of specific testis tumors – Retroperitoneal lymph nodes measuring

has been described. 1–2 cm are confirmed to be pathologically
– The ultrasonographic features, while sugges- involved with metastatic tumor in approxi-
tive, are not diagnostic. mately 70 % of cases.
– When the clinical findings and ultrasound are • Patients with rhabdomyosarcomas require chest
suggestive of malignancy, a computerized radiography, abdominal-pelvic CT scanning,
tomography (CT) scan of the abdomen and bone scanning, and bone-marrow aspiration.
pelvis is obtained to identify retroperitoneal
involvement.
– Benign tumors tend to be well-circumscribed 27.8 Treatment
with sharp borders and decreased blood flow
on Doppler studies. • A solid scrotal mass should be considered
– Epidermoid cysts usually demonstrate echo- malignant until proved otherwise.
genic debris within the well-defined cyst. • Any suspicion of the testicular tumor warrants
– Yolk sac tumors tend to be more solid in an inguinal approach to prevent scrotal viola-
appearance. tion by the tumor.
– The typical testicular tumor is intratesticu- • High inguinal orchiectomy has been a stan-
lar and may produce one or more discrete dard surgical treatment.
hypoechoic masses or diffuse abnormalities • Current trends emphasize that testis-sparing
with microcalcifications that can be surgery should be performed for benign lesions
detected. such as teratoma, leydig cell tumor, and epi-
– Calcifications are more frequent in seminoma dermoid cyst based on frozen biopsy findings.
than in nonseminomatous tumors. • The three basic types of treatment are surgery,
– When the clinical findings and ultrasound are radiation therapy, and chemotherapy.
suggestive of a benign tumor, no further evalu- • In most patients with testicular cancer, the dis-
ation is undertaken. ease is cured readily with minimal long-term
• CT scan and MRI of the abdomen and pelvis morbidity.
(Figs. 27.11 and 27.12): • Stage 1 tumors: Orchiectomy followed by
– This is important in determining the extent surveillance.
of the tumor. • Surveillance includes:
– It is also valuable in identifying the – Frequent physical examinations.
presence and extent of retroperitoneal – Radiographic evaluation of the chest and
lymphadenopathy. retroperitoneum.
– Serum tumor marker measurement. • While treatment success depends on the stage,
– Patients who developed metastatic disease the average survival rate after 5 years is around
are treated with two to four courses of mul- 95 %, and stage 1 cancers cases if monitored
tiagent platinum-based chemotherapy. properly have essentially a 100 % survival
– Patients who present with locally advanced rate.
disease, metastases, or persistently ele- • Inguinal orchiectomy:
vated serum tumor markers are similarly – The initial treatment for testicular cancer is
treated with multiagent platinum-based surgery to remove the affected testicle.
chemotherapy. – This is to be done through an inguinal
• An elevated AFP level in a child over 1 year of approach and never through the scrotum.
age virtually always reflects the presence of a – The lymphatic drainage of the scrotum is
yolk sac tumor and precludes a testis-sparing into the lower legs, while the lymphatic
approach. drainage of the testicles is into the abdo-
• However, in all infants, and in older children men and retroperitoneal lymph nodes.
with a normal AFP, the likelihood of a benign – For this reason, transscrotal testicular
tumor is considerable. biopsy is not recommended.
• This is also true in boys presenting with • Retroperitoneal Lymph Node Dissection:
androgenization. – In the case of nonseminomas that appear to
• However, in adolescents with normal tumor be stage I, retroperitonea lymph node dis-
markers and an ultrasound appearance highly section may be done to accurately deter-
suggestive of a benign lesion, such as an epi- mine whether the cancer is in stage I or
dermoid cyst, testis-sparing may be stage II and to reduce the risk of metastasis
considered. to the retroperitonal lymph nodes.
• A testis-sparing approach: – This approach, while standard in many
– Through an inguinal approach. places, it is not the standard approach
– The testis is delivered into the inguinal due to costs and the high level of exper-
incision. tise required to perform successful
– The cord is occluded with a non-crushing surgery.
clamp or vessel loop. • Adjuvant treatment:
– The tunica vaginalis is opened. – Perhaps the greatest advance in the man-
– The tumor is excised or enucleated and sent agement of testicular cancer was the intro-
for frozen section. duction of platinum-based chemotherapy.
– If a benign histology is confirmed, then the – Survival for both prepubertal and adult
testicular defect is closed with absorbable tumors has increased dramatically since its
suture and the testis is returned to the introduction.
scrotum. – Indeed, multiagent chemotherapy has become
– If a malignancy is detected, or the frozen the standard therapy for virtually all meta-
section is nondiagnostic, then an orchiec- static prepubertal testicular malignancies.
tomy is performed. – Following excision of the primary tumor,
– Reports from small series suggest that this universally benign tumors require no fur-
approach is safe and is effective in preserv- ther evaluation or treatment.
ing testicular tissue. – Treatment options for potentially malig-
– The lesions successfully treated with tumor nant tumors include surveillance, chemo-
enucleation included: therapy, retroperitoneal lymph node
• Teratomas dissection, and radiation therapy.
• Epidermoid cysts – Since testicular cancers can spread, patients
• Sertoli cell tumors are usually offered adjuvant treatment in
• Leydig cell tumors the form of chemotherapy or radiotherapy.
27.9 Yolk Sac Tumor 585
– The type of adjuvant therapy depends • Radiation therapy:

largely on the histology of the tumor and – Radiation may be used to treat stage 2 sem-
the stage of the tumor at the time of inoma cancers, or as adjuvant therapy in
surgery. the case of stage 1 seminomas, to minimize
– If the cancer is not advanced, patients may the likelihood of tumor spread.
be offered careful surveillance by periodic – Radiation therapy is ineffective and is not
CT scans and blood tests, in place of adju- used to treat nonseminoma tumors.
vant treatment. • Chemotherapy:
– For many patients with stage I cancer, adju- – Non-seminoma:
vant therapy following surgery may not be • Chemotherapy is the standard treatment
appropriate and patients will undergo sur- for non-seminoma when the cancer has
veillance instead. spread to other parts of the body (that is,
– This approach ensures that chemotherapy stage 2B or 3).
and or radiotherapy is only given to the • The standard chemotherapy protocol is
patients that need it three, or sometimes four, cycles of
– Virtually all germ cell tumors are sensitive Bleomycin-Etoposide-Cisplatin.
to platinum-based multiagent chemother- • An alternative, equally effective treat-
apy which plays a major role in their ment involves the use of four cycles of
management. Etoposide-Cisplatin.
– Retroperitoneal lymph node dissection • Retroperitoneal lymph node dissec-
plays an important staging and therapeutic tion may also be performed after che-
role for mixed germ cell tumors in motherapy to remove masses left
adolescents, but is rarely employed in cases behind (stage 2B or more advanced),
of prepubertal yolk sac tumor. particularly in the cases of large
– Radiation therapy is primarily used in nonseminomas.
treating seminoma – a very rare tumor in – Seminoma:
the pediatric population. • As an adjuvant treatment, the use of
– The specific adjuvant therapy for a given chemotherapy as an alternative to radia-
patient is dependent on tumor histology tion therapy in the treatment of semi-
and stage. noma is increasing.
– The appropriate surgical treatment for any • Radiation therapy appears to have more
patient with suspected testicular tumor is significant long-term side effects.
radical inguinal orchiectomy with high • Two doses, or occasionally a single dose
ligation of the spermatic cord. of carboplatin, typically delivered
– Transscrotal biopsy or transscrotal orchiec- 3 weeks apart, is proving to be a suc-
tomy is inappropriate and should be cessful adjuvant treatment.
avoided. • Seminomas can recur decades after the
– Adjuvant moderate-dose pelvic and/or primary tumor is removed. This calls for
paraaortic radiotherapy remains the stan- a close and long-term follow-up.
dard treatment for patients with early-stage
seminoma (stage I, IIA, or IIB) after
orchiectomy. 27.9 Yolk Sac Tumor
– Patients who are found to have more
advanced disease (stage IIC, III, IV) have a • Pure yolk sac tumors occur almost exclusively
high risk of systemic relapse if treated with in infants and very young children.
surgery and radiation alone, and the stan- • Histologic evaluation of the yolk-sac tumor
dard treatment for these patients is combi- demonstrates eosinophilic periodic acid-
nation chemotherapy. Schiff (PAS)–positive inclusions in the
cytoplasm of clear cells that consist of AFP radiographic evaluation of the chest and retro-
and Schiller-Duval bodies. peritoneum, and serum tumor marker
• Nearly all are managed with surveillance or measurement.
platinum-based chemotherapy. • Patients who developed metastatic disease are
• Current chemotherapeutic regimens for yolk- treated with two to four courses of multiagent
sac tumors are platinum-based protocols. platinum-based chemotherapy.
Common agents include etoposide, bleomy- • Patients who present with locally advanced
cin, and cisplatin. disease, metastases, or persistently elevated
• Follow-up should include monthly tests of serum tumor markers are similarly treated with
serum AFP levels, chest radiography every multiagent platinum-based chemotherapy.
2 months for 2 years, and CT scanning or MRI • The survival for all patients with this approach
of the retroperitoneum every 3 months for the was nearly 100 %.
first year and then biannually.
• Because spread to the retroperitoneal lymph
nodes is uncommon, routine prophylactic dis- 27.10 Teratoma
section of the nodes is not performed.
• Chemotherapy is administered in patients • While metastatic disease occurs in up to 60 %
with radiographic evidence of metastatic dis- of adults with teratoma, these tumors are uni-
ease or persistently elevated serum AFP lev- versally benign in pre-pubertal patients.
els. The use of combination chemotherapy • Adolescents with teratoma should undergo
with cisplatin, etoposide, and bleomycin has orchiectomy and a metastatic evaluation fol-
been an effective treatment for metastatic dis- lowed by surveillance for stage 1 disease.
ease, with a survival rate approaching 90 %. • Because of its benign nature, prepubertal tera-
• More than 99 % of all patients with yolk-sac toma can be managed with testis-sparing surgery.
tumors are expected to survive. • Teratomas and teratocarcinomas contain ele-
• Retroperitoneal lymph node dissection, which ments derived from more than one of the three
plays a central role in the staging and therapy germ tissues: endoderm, mesoderm, and ecto-
of adults with mixed germ cell tumors, is derm. These tumors are often cystic, and tis-
rarely employed in children. sues such as skin, hair, bone, and even teeth
• This is in part because prepubertal patients are may be present. Although they contain areas
less likely than adults to have metastases lim- of poorly differentiated cells with a malignant
ited to the retroperitoneum. appearance, teratomas are consistently benign
• Furthermore 80 % of prepubertal patients have in children younger than 2 years.
clinical stage 1 disease and fewer than 20 % will • The vast majority of prepubertal teratomas are
recur with no therapy beyond orchiectomy. “mature” teratomas, and for these tumors, no
• Finally, the morbidity of retroperitoneal further treatment or follow-up is necessary.
lymph node dissection is likely to be greater in • Immature teratomas are characterized by the
children than in adolescents and adult. presence of embryonal or incompletely
• In children, retroperitoneal surgery is reserved differentiated tissue components, most com-
for biopsy of radiographically equivocal nodes monly primitive neuroectodermal structures.
or for resection of a persistent retroperitoneal • There is some uncertainty regarding the
mass following chemotherapy. behavior of immature teratomas.
• The specific management for patients with • Pediatric immature teratomas (regardless of
yolk sac tumor has been defined by several site) generally behave in a benign fashion if
multicenter clinical trials. completely resected.
• Stage 1 tumors are managed with orchiectomy • Somatic malignancies may also arise in imma-
followed by surveillance. Surveillance ture teratomas leading to metastatic spread.
includes frequent physical examinations, This is exceedingly rare in children.
27.12 Stromal Tumors 587
• Furthermore, if foci of yolk sac tumor are • If microscopically positive nodes are found at
found in an immature teratoma, then it should the time of retroperitoneal lymph node dissec-
be treated as a yolk sac tumor. tion, these patients are treated with a course of
• While immature teratomas of the testis can be chemotherapy.
managed with complete tumor resection • Patients with radiographic evidence of meta-
alone, these patients should be followed-up. static disease at presentation or persistently
• Epidermoid cysts are composed entirely of elevated tumor markers following orchiec-
keratin-producing squamous epithelium and tomy are treated with three to four cycles of
are universally benign in children and adults. chemotherapy.
• They can be treated by tumor enucleation with • The relapse rate following primary chemo-
no chemotherapy or follow-up. therapy for metastatic disease is approxi-
mately 15 %, though it may be as high as 30 %
for poor-risk patients.
27.11 Mixed Germ Cell Tumor • Retroperitoneal lymph node dissection may
be considered for patients with very limited
• Mixed germ cell tumors are rare in pre- retroperitoneal lymph node disease at presen-
pubertal patients, but account for a significant tation and normalization of tumor markers
proportion of testis tumors in adolescents. after orchiectomy.
• These tumors are managed as adults with • Some patients with mixed germ cell tumors
observation, retroperitoneal lymph node dis- treated with chemotherapy for metastatic dis-
section and/or chemotherapy depending on ease will have a residual retroperitoneal mass
the specific histology and stage of the following therapy.
disease. • If tumor markers have normalized, these
• Patients with stage 1 mixed germ cell tumors residual masses should generally be resected.
may be managed with surveillance. – 40–50 % of residual masses will contain
• The recurrence rate on surveillance is only necrotic tissue and fibrosis.
25–30 %. – 10–20 % will have persistent malignancy.
• Recurrence may be prevented with a modified – 40–45 % will contain mature teratoma.
nerve-sparing retroperitoneal lymph node dis-
section or two cycles of platinum-based che-
motherapy, but this “over-treats” the 70–75 % 27.12 Stromal Tumors
of patients who do not have occult metastatic
disease. • Stromal tumors of the testis are rare in chil-
• On the other hand, when recurrence occurs on dren and adolescents.
surveillance, more intense therapy is required. • Leydig cell tumors and juvenile granulosa cell
• Patients with low risk disease are usually fol- tumors are universally benign in children.
lowed with frequent chest x-rays, tumor marker • Leydig cell tumors:
measurements and abdominal CT scans. – These are the second most common
• Nearly all recurrences occur within 2 years of gonadal stromal tumors in children and are
orchiectomy and are treated with also benign.
chemotherapy. – Leydig cell tumors usually present between
• Patients at higher risk for recurrence generally 5 and 10 years of age with precocious
undergo a modified nerve-sparing retroperito- puberty.
neal lymph node dissection: – The synthesis of testosterone may produce
– Those with vascular invasion precocious puberty, gynecomastia, and ele-
– Largely embryonal cell histology vated levels of 17-ketosteroids.
– Those who are poorly compliant with – Leydig-cell tumors must be differentiated
therapy from hyperplastic nodules that develop in
boys with poorly controlled congenital produce no endocrinologic effects; how-

adrenal hyperplasia (CAH). ever, 14 % of patients present with
– They may be treated with orchiectomy or gynecomastia.
tumor enucleation. – Approximately 10 % of adult Sertoli cell
– Contralateral tumors may also occur, tumors are malignant, malignancy however
though they are rare in children. is very rare in children.
• Adrenal rests: – All reported cases of Sertoli cell tumors in
– Adrenal rests along the spermatic cord and children under 5 years of age are benign
in the testicular hilum may hypertrophy in but there have been a few cases of malig-
patients with precocious puberty due to nant Sertoli cell tumors in older children.
congenital adrenal hyperplasia mimicking – Therefore, children younger than 5 years
a Leydig cell tumor. are adequately treated with orchiectomy
– In patients with congenital adrenal hyper- and do not require metastatic evaluation.
plasia the nodules are often multifocal and – Older children should undergo chest radi-
bilateral. ography and abdominal CT scanning to
– The diagnosis of congenital adrenal rule out metastases.
hyperplasia can generally be made by – Tumor excision is usually adequate treat-
demonstrating an elevated serum ment for infants, but a metastatic evalua-
17-hydroxyprogesterone level. tion should be considered such as:
– The nodules will usually resolve or signifi- • Large tumor size
cantly reduce in size with steroid replace- • Areas of necrosis
ment therapy for congenital adrenal • Vascular invasion
hyperplasia. If this occurs, the patient may • Cellular atypia
be followed with serial examinations. • Increased mitotic activity.
– Large nodules that fail to regress may be – Older children with Sertoli cell tumors
safely enucleated. should undergo a full metastatic evaluation.
• Juvenile granulosa tumors: – Metastases are treated with a combination
– These account for approximately 3 % of all of radiotherapy, chemotherapy, and retro-
neonatal testicular tumors and commonly peritoneal lymph node dissection.
appear as cystic, painless testicular masses. – Large-cell calcifying Sertoli cell tumors:
– Juvenile granulosa cell tumors occur • These are clinically and histologically
almost exclusively in the first year of life, distinct tumors which occur predomi-
most commonly in the first 6 months. nantly in children and adolescents.
– Chromosomal mosaicism, structural abnor- • These tumors are composed of large
malities of the Y chromosome, and ambig- cells with abundant cytoplasm and vary-
uous genitalia are common in boys with ing degrees of calcification.
juvenile granulosa cell tumor. • Approximately one third of patients
– These tumors are hormonally inactive and have an associated genetic syndrome
benign. and/or endocrine abnormality, the most
– Although these children should undergo a common being Peutz-Jeghers syndrome
chromosomal analysis, the tumor itself and Carney’s syndrome.
may be treated by orchiectomy or tumor • Peutz-Jeghers syndrome is an autoso-
enucleation with no metastatic evaluation mal dominant disorder consisting of
or adjuvant therapy. mucocutaneous pigmentation and ham-
• Sertoli cell tumors: artomatous intestinal polyposis.
– These are the most common gonadal stro- • Features of Carney syndrome include
mal tumors in prepubertal children. myxomas of the skin, soft tissue, and
– These tumors tend to appear as painless heart; myxoid lesions of the breast; len-
masses in boys younger than 6 months and tigines of the face and lips; cutaneous
27.15 Testicular Microlithiasis (TM) 589
blue nevi; Cushing syndrome; pituitary • Associated genitourinary anomalies, particu-

adenoma; and schwannoma. larly renal agenesis, are common. Therefore,
• Patients and first-degree relatives of patients with cystic dysplasia of the rete testis
patients with large-cell calcifying should undergo upper tract imaging.
Sertoli cell tumor should be screened
for these potentially serious syndromes.
• Whereas these tumors are occasionally 27.14 Epidermoid Cysts
malignant in adults, they have been uni-
versally benign in patients under • These are benign tumors of epithelial origin
25 years of age. and account for 10–15 % of cases.
• Orchiectomy is sufficient treatment in • These probably represent a monodermal vari-
children, but approximately one fourth ant of teratoma.
of patients will have bilateral and/or • Epidermoid cysts are composed entirely of
multifocal disease. keratin-producing squamous epithelium and
• A testis-sparing approach has been are universally benign in children and
described for this rare tumor. adults.
• A mixed or poorly differentiated stromal • They can often be suspected by their typical
tumor: appearance on ultrasound of a cyst filled with
– Rarely a prepubertal patient may have a echogenic layered debris (corresponding to
mixed or poorly differentiated stromal the desquamated keratin) giving an “onion-
tumor. skin” appearance.
– Most of these tumors are benign. • They may be treated by tumor enucleation
– Malignancy should be considered in those with no oncological evaluation or follow-up.
with: • They are often firm and well-defined, with a
• A large number of mitotic figures central hypoechoic region or mixed internal
• A tumor that is poorly differentiated echogenicity surrounded by an echogenic rim
• Local invasion. on ultrasonography.
– Orchiectomy is the treatment of choice. • Following tumor enucleation, these tumors do
– Retroperitoneal lymph node dissection and not require follow-up.
adjuvant therapy are indicated in those
with metastatic disease.
– These patients should be followed-up 27.15 Testicular Microlithiasis (TM)
closely for the development of metastatic
disease. • This has been identified as a possible risk
factor for the development of testicular
cancer.
27.13 Simple Testicular Cyst • TM refers to the presence of microcalcifica-
tions, usually diffuse, within the parenchyma
• Simple testicular cysts may be observed but if of the testis on ultrasound.
large in size, they should be excised. • The association with testicular malignancies
• Cystic dysplasia of the rete testis is a benign was suggested by the finding that approxi-
tumor found primarily in children. mately 25 % of adult testes harboring cancer
• Ultrasound typically reveals multiple small are found to have TM.
cysts arising from the testicular hilum, some- • But the causal relationship behind this finding
times compressing the normal testicular is unclear.
parenchyma. • TM is found incidentally in approximately
• These tumors are universally benign and may 2 % of boys and men undergoing ultrasound
be managed by observation, tumor excision, either for testicular symptoms or as part of a
or orchiectomy if extensive. screening study of asymptomatic males.
• There is still insufficient data to quantify the • Gonadectomy is sufficient treatment for
risk, if any, of testicular cancer in boys or men gonadoblastoma.
incidentally found to have TM. • If malignant degeneration has occurred, then
• Studies suggest that TM may be most signifi- further therapy may be warranted.
cant when it occurs in conjunction with other • When malignancies occur, dysgerminoma is
risk factors for testicular cancer, such as men the most common histological type.
with infertility or a history of contralateral tes- • These tumors are very radiosensitive and the
ticular cancer. outlook for these patients is generally
favorable.
• These occurs in association with disorders of
27.16 Gonadoblastoma sexual development (intersex).
• About 80 % of cases involve phenotypic
• While rare, certain disorders of sexual devel- females with intra-abdominal testes or streak
opment (DSD) harbor a very significant risk gonads.
for the development of gonadal tumors. • The putative gonadoblastoma gene is on the Y
• Some disorders, such as complete androgen chromosome, and the tumor almost always
insensitivity syndrome, have an increased risk develops in a child with a Y chromosome. The
comparable to that of other patients with tes- streak gonads in patients with mixed gonadal
ticular maldescent. dysgenesis often develop gonadoblastomas.
• But unique to patients with DSD are the risks • The incidence peaks at puberty, and early
of tumor formation in dysgenetic or streak gonadectomy is recommended in patients at
gonads. This risk seems to exist almost exclu- risk for gonadoblastoma.
sively in patients with Y chromatin. • Metastatic spread of a gonadoblastoma occurs
• For example, patients with Turner syndrome in 10 % of patients.
and any portion of a Y chromosome in their • These tumors may elevate serum levels of beta-
karyotype have an approximately 12 % risk of human chorionic gonadotropin (beta-HCG).
tumor development; while patients with tradi-
tional Turner syndrome and a 45 XO karyo-
type are at no significant risk for gonadal 27.17 Cystic Dysplasia of the Testes
tumors.
• Similarly the gonads of patients with pure • This is a benign lesion that is often associated
gonadal dysgenesis and Y chromatin as well with ipsilateral renal agenesis or dysplasia.
as the “streak” gonad of patients with mixed • This association, along with a characteristic
gonadal dysgenesis are at a 15–30 % risk for ultrasonographic appearance (i.e., hypoechoic
tumor development. lesions), permits preoperative diagnosis and
• The tumors arising in the setting of gonadal possible treatment with testicular-sparing
dysgenesis are usually gonadoblastomas. surgery.
• While gonadoblastomas are benign, they are
prone to the development of malignant
degeneration and overt malignant behavior is 27.18 Leukemia and Lymphoma
seen in 10 % of cases.
• While most cases of malignancy occur after • These are the most common secondary malig-
puberty, there have been cases reported in nancies to affect the testis.
children as well. • These tumors can present bilaterally, and,
• Prophylactic removal of dysgenetic gonads because the blood-testis barrier protects the
should be undertaken early in life in patients intratesticular cells, the testis may be the site
with at-risk karyotypes.
27.19 Paratesticular Rhabdomyosarcoma 591
of residual tumor in children after of metastatic disease may require radiation

chemotherapy. therapy.
• Metastatic disease to the testes should be con- • Routine dissection of the retroperitoneal
sidered in a child presenting with bilateral tes- lymph nodes is recommended in all patients
ticular tumors. aged 10 years or older (regardless of the imag-
• Paratesticular structures can give rise to vari- ing results) and in patients younger than
ous benign (lipoma, leiomyoma, hemangi- 10 years whose images show retroperitoneal
oma, or fibroma) and malignant tumors; disease.
however, these are extremely rare. • Children younger than 10 years have a sur-
vival rate of nearly 95 %. Children older than
10 years have a worse prognosis and an
27.19 Paratesticular increased risk for involvement of the retroper-
Rhabdomyosarcoma itoneal lymph nodes; therefore, an aggressive
approach with dissection of the retroperito-
• This is the most common malignant tumor neal lymph nodes is recommended.
(17 %) and may arise from the distal spermatic • Paratesticular rhabdomyosarcoma should be
cord and appear as a scrotal mass or evaluated for metastasis including:
hydrocele. – CT of the chest, abdomen, and pelvis.
• These tumors have a bimodal distribution and – The most common sites of metastases are
occur in boys aged 3–4 months and in the retroperitoneum and lungs.
teenagers. • Patients with retroperitoneal metastases
• Up to 70 % of cases involve the retroperitoneal undergo a modified unilateral nerve-sparing
lymph nodes at presentation. retroperitoneal lymph node dissection.
• About 90 % of paratesticular rhabdomyosar- • All patients are treated with chemotherapy
comas demonstrate a favorable embryonal and those with positive retroperitoneal nodes
pattern on histology. receive radiation therapy as well.
• Paratesticular rhabdomyosarcomas usually • Younger children with a normal abdominal
present with an enlarging painless scrotal CT may be treated with chemotherapy alone
mass. without a staging retroperitoneal lymph node
• By the time of presentation distinction from a dissection.
primary testicular tumor is usually not possi- • The role of staging RPLND in patients with
ble on physical examination, though the clinical stage 1 disease is based on experience
extratesticular nature of the tumor is usually in the Intergroup Rhabdomyosarcoma Studies
apparent on ultrasound (IRS).
• The initial management for paratesticular – IRS-III (from 1984 to 1991) required a
rhabdomyosarcomas is an inguinal excision of staging unilateral RPLND for all clinical
the tumor and testis. stage 1 patients.
• The excision should be performed just as for a – In IRS-IV (from 1991 to 1997) patients
testicular malignancy. with a negative CT scan did not undergo
• Trans-scrotal biopsies of solid scrotal masses staging RPLND (and did not receive radia-
should be avoided due to the risk of seeding of tion to the retroperitoneum).
the incision if the mass is indeed a • This approach resulted in a worrisome
rhabdomyosarcoma. decrease in the percentage of patients diag-
• All children with rhabdomyosarcoma require nosed with metastatic disease in IRS-IV, par-
vincristine, Adriamycin, and dactinomycin ticularly among adolescents.
(VAC) chemotherapy or treatment with a com- • Furthermore, adolescents with clinical stage 1
bination of these drugs. Patients with evidence disease in IRS-IV had a 3-year event-free
survival (EFS) of only 68 % compared to a • Since the introduction of adjuvant chemother-

100 % survival for patients with recognized apy, chiefly platinum-based drugs like cispla-
lymph node involvement (who received radia- tin and carboplatin, the outlook has improved
tion and more intense chemotherapy) presum- substantially.
ably due to under-staging and under-treatment • The survival rates have improved markedly
of those stage 1 patients with occult retroperi- and currently the cure rates are over 95 %.
toneal disease. • With recent advances in radiologic staging,
• Such discrepancies were not seen in the pre- serum tumor marker surveillance, and
pubertal patients. platinum-based chemotherapy for advanced
• Based on these data, patients over 10 years of disease, overall survival rates for patients with
age with or without radiographic evidence of seminoma have increased to more than 90 %.
retroperitoneal disease should undergo a stag- • Nearly 100 % of patients with stage I testicular
ing RPLND and receive radiation in addition seminoma are cured.
to chemotherapy if the lymph nodes are
positive.
• Younger children with a normal abdominal Further Reading
CT may be treated with chemotherapy alone
without a staging RPLND. 1. Agarwal PK, Palmer JS. Testicular and paratesticular
neoplasms in prepubertal males. J Urol. 2006;176(3):
• These tumors are highly aggressive and spread
875–81.
via the blood, lymphatics, or direct extension 2. Bujons A, Sfulcini JC, Pascual M, Feu OA, Garat JM,
to the lungs, the cortical bone, or to the bone Villavicencio H. Prepubertal testicular tumours and
marrow in 20 % of patients at the time of efficacy of testicular preserving surgery. BJU Int.
2011;107(11):1812–6.
diagnosis.
3. Carver B, Al-Ahmadie H, Sheinfeld J. Adult and pedi-
• Radical inguinal orchiectomy followed by ret- atric testicular teratoma. Urol Clin N Am. 2007;34:
roperitoneal lymph node dissection is recom- 245–51.
mended for all children older than 10 years 4. Cornejo KM, Frazier L, Lee RS, Kozakewich HP,
Young RH. Yolk sac tumor of the testis in infants and
and for those younger than 10 years with ret-
children: a clinicopathologic analysis of 33 cases. Am
roperitoneal disease. J Surg Pathol. 2015;39(8):1121–31.
• Patients with positive lymph nodes are treated 5. Cortez J, Kaplan G. Gonadal stromal tumors, gonado-
with multimodal therapy (chemotherapy and blastomas, epidermoid cysts, and secondary tumors of
the testis in children. Urol Clin North Am.
radiation).
1993;20:15–26.
• The overall survival rates for patients with 6. Cost NG, Lubahn JD, Adibi M, Romman A, Wickiser
paratesticular rhabdomyosarcoma is currently JE, Raj GV, et al. Risk stratification of pubertal chil-
about 90 %. dren and postpubertal adolescents with clinical stage I
testicular nonseminomatous germ cell tumors. J Urol.
2014;191(5 Suppl):1485–90.
7. Cushing B, Giller R, Cullen J, et al. Randomized
27.20 Prognosis and Outcome comparison of combination chemotherapy with eto-
poside, bleomycin, and either high-dose or standard-
dose cisplatin in children and adolescents with
• In the past, the survival rates from testicular
high-risk malignant germ cell tumors: a pediatric
cancer were low. intergroup study – Pediatric Oncology Group 9049
• Perhaps the greatest advance in the manage- and Children’s Cancer Group 8882. J Clin Oncol.
ment of testicular cancer was the introduction 2004;22:2691–700.
8. Furness PD, Husman DA, Brock JW, et al. Multi-
of platinum-based chemotherapy.
institutional study of testicular microlithiasis in child-
• Survival for both prepubertal and adult tumors hood: a benign or premalignant condition? J Urol.
has increased dramatically since its introduction. 1998;160:1151–4.
• Multiagent chemotherapy has become the 9. Hisamatsu E, Takagi S, Nakagawa Y, Sugita Y,
Yoshino K, Ueoka K, et al. Prepubertal testicular
standard therapy for virtually all metastatic
tumors: a 20-year experience with 40 cases. Int J Urol.
prepubertal testicular malignancies. 2010;17(11):956–9.
Further Reading 593
10. Kao CS, Cornejo KM, Ulbright TM, Young RH. 16. Ross JH, Rybicki L, Kay R. Clinical behavior and a
Juvenile granulosa cell tumors of the testis: a clinico- contemporary management algorithm for prepubertal
pathologic study of 70 cases with emphasis on its testis tumors: a summary of the Prepubertal Testis
wide morphologic spectrum. Am J Surg Pathol. Tumor Registry. J Urol. 2002;168(4 Pt 2):1675–8.
2015;39(9):1159–69. 17. Rushton H, Belman A, Sesterhenn I, et al. Testicular spar-
11. Mann J, Raafat F, Robinson K, et al. The United ing surgery for prepubertal teratoma of the testis: a clini-
Kingdom Children’s Cancer Study Group’s second cal and pathological study. J Urol. 1990;144:726–30.
germ cell tumor study: carboplatin, etoposide, and 18. Schneider D, Calaminus G, Koch S, et al.
bleomycin are effective treatment for children with Epidemiologic analysis of 1,442 children and adoles-
malignant extracranial germ cell tumors, with accept- cents registered in the German germ cell tumor proto-
able toxicity. J Clin Oncol. 2000;18:3809–18. cols. Pediatr Blood Cancer. 2004;42:169–75.
12. Metcalfe PD, Farivar-Mohseni H, Farhat W, McLorie 19. Thomas J, Ross J, Kay R. Stromal testis tumors in
G, Khoury A, Bagli DJ. Pediatric testicular tumors: children: a report from the prepubertal testis tumor
contemporary incidence and efficacy of testicular pre- registry. J Urol. 2001;166:2338–40.
serving surgery. J Urol. 2003;170(6 Pt 1):2412–5. 20. Thomas JC, Ross JH, Kay R. Stromal testis tumors in
13. Petkovic V, Salemi S, Vassella E, et al. Leydig-cell children: a report from the prepubertal testis tumor
tumour in children: variable clinical presentation, registry. J Urol. 2001;166(6):2338–40.
diagnostic features, follow-up and genetic analysis of 21. Valla J. Testis-sparing surgery for benign testicular
four cases. Horm Res. 2007;67:89–95. tumors in children. J Urol. 2001;165:2280.
14. Petterson A, Richiardi L, Nordenskjold A, et al. Age 22. Walsh TJ, Grady RW, Porter MP, et al. Incidence of
at surgery for undescended testis and risk of testicular testicular germ cell cancers in U.S. children: SEER
cancer. NEJM. 2007;356:1835–41. program experience 1973 to 2000. Urology. 2006;6:
15. Ross J, Rybicki L, Kay R. Clinical behavior and a 402–5.
contemporary management algorithm for prepubertal 23. Young R, Koelliker D, Scully R. Sertoli cell tumors of the
testis tumors: a summary of the Prepubertal Testis testis, not otherwise specified: a clinicopathologic analy-
Tumor Registry. J Urol. 2002;168:1675–9. sis of 60 cases. Am J Surg Pathol. 1998;22:709–21.
Splenogonadal Fusion
28
28.1 Introduction • It is seen nearly always on the left side.

• Splenogonadal fusion typically presents as an
• Splenogonadal fusion is a rare congenital mal- asymptomatic testicular mass.
formation that results from an abnormal fusion • Other manifestations may include acute tes-
between the primitive spleen and gonad. ticular pain and swelling caused by ectopic
• Splenogonadal fusion is a rare, benign, con- splenic tissue infections.
genital anomaly thought to occur between the • Splenogonadal fusion is a very rare congenital
fifth and eighth weeks of intrauterine life anomaly that must be kept in mind and thought
where immature splenic tissue adheres to the of especially if a child presents with an
developing gonad, epididymis or vas deferens. unusual scrotal swelling.
The splenic tissue is subsequently pulled in a • It is rarely diagnosed preoperatively.
caudal direction with descent of the gonad. • If suspected preoperatively, the diagnosis can
• It was first described in 1883 by Bostroem. be confirmed by a 99mTc-sulphur colloid scan.
• Since then more than 200 cases of splenogo- • There are two types of splenogonadal fusion,
nadal fusion have been described in the litera- continuous and discontinuous.
ture, most of them are single case reports. • In continuous splenogonadal fusion there
• Its first categorization was made in 1956 by remains a connection between the main spleen
Putschar and Manion. and gonad.
• Karaman and Gonzales in 1996 reviewed 137 • In discontinuous splenogonadal fusion, ecto-
cases of splenogonadal fusion and surpris- pic splenic tissue is attached to the gonad, but
ingly 37 % of the patients had orchiectomy there is no connection to the main spleen.
because of suspicion of a testicular tumor. • The continuous form occurs when the nor-
• This is of great importance and to obviate this mally located spleen is attached to the gonad
physicians caring for these patients should be by a discrete cord.
aware of this and intra-operatively if there is • In the discontinuous type the splenic tissue is
doubt concerning the nature of the swelling, attached to the gonad and completely sepa-
intra-operative frozen section biopsy should be rated from the normal spleen.
performed to avoid unnecessary orchiectomy. • Both types occur with equal frequency and the
• Splenogonadal fusion occurs more commonly discontinuous type may be discovered inciden-
in males with a male-to-female ratio of 15:1. tally during herniotomy or orchidopexy or pres-
This figure may of course be inaccurate due to ent as a scrotal swelling. Awareness of this is of
the relative inaccessibility of the ovary to clin- great importance to avoid unnecessary orchiec-
ical examination. tomy mistaken it for a testicular tumor (Fig. 28.1).

596 28 Splenogonadal Fusion
• Splenogonadal fusion is thought to result from

partial fusion of splenic and gonadal tissues in
the fourth to eighth weeks of intra-uterine life.
• Subsequent descent of the gonad during the
eighth to tenth weeks of gestation results in
descent of a part of the developing spleen
along with it.
• In the discontinuous type, there is complete
detachment from the normal spleen while in
the continuous type there is attachment to the
normal spleen by a cord-like structure.
– This cord can be made up of splenic tissue
Fig. 28.1 A clinical intraoperative photograph of spleno- or totally fibrotic.
gonadal fusion diagnosed in a child with unusual testicu-
lar swelling
– Occasionally, there are multiple nodules
along this cord which represent foci of
splenic tissue that got detached and devel-
• Treatment is surgical excision and every oped separately. This however does not
attempt should be made to preserve the gonad fully explain the occasional occurrence of
at the time of dissection and excision which right sided Splenogonadal fusion.
should not be difficult since true fusion with • It has been postulated that contact between the
the gonad is rare. gonadal ridge and the primitive spleen pre-
• Although there have been few reports of an cipitated by stress factors (vascular or other-
association of testicular neoplasms with sple- wise) may be responsible for a continuous
nogonadal fusion, it appears that this is a coin- splenogonadal fusion.
cidental finding rather than an association as • A more recent hypothesis is based on the
these tumors occurred in adults with unde- capacity of splenic cells to migrate at early
scended testes. stages of development. The spleen is partly
• The diagnosis of splenogonadal fusion should responsible for the development of blood cells
always be kept in mind and included in the dif- in the fifth week of gestation. A migration and
ferential diagnosis of testicular swelling in colonization of splenic cells to its nearby
infants and children (Fig. 28.1). structures namely the gonadal anlage could be
responsible for both splenogonadal fusion as
well as the explanation for its high association
28.2 Etiology to cryptorchidism.
• It is important to note that the splenic and the
• The exact etiology of splenogonadal fusion is testicular tissue of splenogonadal fusion are
not known. normal hence orchiectomy or splenectomy is
• Embryologically, the testis starts to descend not indicated.
from its initial embryological position
between the dorsal mesogastrium and the
mesonephros at around the eighth week of 28.3 Classification
intrauterine life.
• This occurs at the time of splenic development. • Putschar and Manion in 1956 and in a collec-
• Embryologically, the spleen is formed by a tive review of 30 cases classified splenogo-
proliferation of mesodermal cells in the dorsal nadal fusion into two types, continuous and
mesogastrium around the fifth and sixth weeks discontinuous.
of gestation. • Splenogonadal fusion is divided into two
• As a result of normal gastric rotation, the types:
spleen moves in front of the gonadal ridge and – Continuous
mesonephros. – Discontinuous
• In the continuous type, there is a direct con- • In cases of continuous splenogonadal fusion,
nection between the normal spleen and gonad 50 % are accompanied by other congenital
by a cord that may be: malformations.
– Totally made up of splenic tissue • The incidence rate of associated anomalies for
– Multiple connected beads of splenic tissue continuous splenogonadal fusion is fivefold
– A cord made up of fibrous tissue higher than that of discontinuous splenogo-
• In the discontinuous type there is no connection nadal fusion and most cases are accompanied
between the normal spleen and ectopic spleen by limb defect syndrome. These are called
that is attached to the gonad. This is considered splenogonadal fusion limb defect syndrome
a rare variant of an accessory spleen. (SGFLD).
• Both types occur with relatively equal • The majority (83 %) of splenogonadal fusion
frequency. limb defect syndrome (SGFLD) are seen in
• Some authors have suggested that because of those with continuous splenogonadal fusion
the high association of continuous splenogo- and 70 % are associated with micrognathia.
nadal fusion with limb defects, continuous • Approximately one-fifth of continuous sple-
fusion should be regarded as an independent nogonadal fusion patients also have other
syndrome classified by its associated defects major congenital defects, such as limb
(limb defects, facial or other structures). hypoplasia, micrognathia, cardiac defects,
palatal defects and anal defects.
28.4 Associated Anomalies

• Splenogonadal fusion is associated to a wide
variety of malformations. • Splenogonadal fusion is commonly asymp-
• Cryptorchidism and inguinal hernias are the tomatic discovered incidentally during routine
most common malformations associated with herniotomy or orchidopexy.
splenogonadal fusion. • Many of these cases however go passed unno-
• In total, 31 % of splenogonadal fusion patients ticed or discovered at autopsy.
are diagnosed with cryptorchidism or inguinal • In the pediatric age group, these patients com-
hernias, and in 59 % of cases the cryptorchi- monly present with a scrotal swelling and may
dism is bilateral. rarely present with an acute scrotal pain as a
• Other malformations include: result of torsion or involvement of splenic tis-
– Limb defects such as peromelia sue with other pathological conditions such as
– Micrognathia mumps, malaria, leukemia, trauma and infec-
– Cleft palate tious mononucleosis.
– Spinal malformations • The left side is far more commonly affected
– Cardiac anomalies than the right in 98 % of the cases.
– Microgastria • It is more common in males with an M: F of
– Osteogenesis imperfecta 15:1. This however may not be true as the
– Spina bifida ovary is not easily accessible and since the
– Congenital diaphragmatic hernia majority of these cases are asymptomatic, the
– Anorectal anomalies incidence of splenogonadal fusion in females
– Craniosynostosis may be underestimated.
– Moebius syndrome • Not uncommonly splenogonadal fusion is
– Roberts’s syndrome which consists of limb associated with other anomalies or discovered
deficiencies, facial anomalies due to pre- during the evaluation of these associated
mature centromere separation anomalies. This is more so with the continu-
• Splenogoadal fusion with limb defects has ous type which is known to be associated with
also been associated to the Hanhart anomaly other associated anomalies in as much as 33 %
and the femoral facial syndrome. of the cases.
598 28 Splenogonadal Fusion
• One of the most common forms of presenta- 28.6 Investigations

tion of splenogonadal fusion is testicular
swelling. • Splenogonadal fusion remains a diagnostic
• This swelling might appear as a hydrocele if it challenge and rarely it is diagnosed
is painless. preoperatively.
• The swelling may be accompanied by pain in • The diagnosis of splenogonadal fusion should
cases where the ectopic splenic tissue is affected always be kept in mind and included in the dif-
by systemic disease, like Malaria, or mumps. ferential diagnosis of testicular swelling in
• Splenogonadal fusion is commonly diagnosed infants and children.
in children and adolescents. • Physicians caring for these patients should be
– The number of cases reported in patients aware of this and preoperative consideration
<10 years of age account for 50 % of the of the diagnosis may help avoid unnecessary
total cases reported. orchiectomy.
– The number of cases reported in patients • The radiologic identification of splenogonadal
<20 years old account for 70 %. fusion is important to prevent unnecessary
• Patients most commonly present under the age orchiectomy due to its macroscopic resem-
of 20 years with: blance to cancer.
– Cryptorchidism • Imaging modalities including ultrasonogra-
– Left inguinal hernia phy, computed tomography (CT), magnetic
– A left scrotal mass resonance imaging (MRI) and 99TCm spleen
• Splenogonadal fusion may be an incidental scanning, aid with the diagnosis of splenogo-
finding during an orchidopexy and in these nadal fusion.
patients it is important to recognize this and • Recently, laparoscopy is used to diagnose and
manage the patient accordingly. manage patients with suspected splenogo-
• The presentation may, however, be due to the nadal fusion.
complications of the splenogonadal fusion • Scrotal ultrasound may show ectopic splenic tis-
including: sue as an encapsulated homogeneous extra tes-
– Intestinal obstruction ticular mass, isoechoic with the normal testis.
– Acute painful scrotal splenic enlargement • The presence of splenic tissue may be con-
– Rupture firmed with a technetium-99m sulfur colloid
• One-third of cases are associated with other scan.
congenital abnormalities including limb and • Often, the definitive diagnosis is made postop-
orofacial malformation. eratively by histology and orchiectomy is not
• These associated anomalies are more likely necessary as the splenic tissue can be dis-
seen in the continuous form. sected off the testicle.
• There is also an association between spleno- • The goal should be to preserve the testis and the
gonadal fusion and testicular malignancy. use of frozen section may be useful in distin-
– In the literature, there are about seven guishing between splenogonadal fusion and pri-
reported cases of splenogonadal fusion and mary testicular and para-testicular neoplasms.
testicular malignancy but in all of these
cases the malignancy developed in adults
with undescended testes or following 28.7 Treatment
orchidopexy for undescended testes.
– This may represents an association rather • Preoperative diagnosis of splenogonadal
than an increased risk in this subset group fusion is uncommon.
of patients as patients with undescended • Intraoperatively, the diagnosis may also be
testes have a well-known increased risk of difficult and it not uncommon for this to be
malignancy. confused with a testicular tumor.
Further Reading 599
• Several patients with splenogonadal fusion 4. Carragher AM. One hundred years of splenogonadal
fusion. Urology. 1990;35:471–5.
have undergone unnecessary orchiectomy due
5. Gouw AS, Elema JD, Bink-Boelkens MT, De Jongh
to the misdiagnosis of a testicular tumor. JH, ten Kate LP. The spectrum of splenogonadal
• Spleen tissue is easily separated from the fusion. Case report and review of 84 reported cases.
gonad and as a result the testis may be saved Eur J Pediatr. 1985;144:316–23.
6. Karaman MI, Gonzales ET. Splenogonadal fusion:
and retained.
report of 2 cases and review of the literature. J Urol.
• If the diagnosis is not clear and a tumor is sus- 1996;155:309–11.
pected, biopsy and frozen section may aid 7. Khairat AB, İsmail AM. Splenogonadal fusion: case
with the diagnosis. presentation and literature review. J Pediatr Surg.
2005;40:1357–60.
• Laparoscopy is a safe and reliable approach
8. Lopes RI, de Medeiros MT, Arap MA, Cocuzza M,
that is highly accurate in the diagnosis and Srougi M, Hallak J. Splenogonadal fusion and testicu-
treatment of nonpalpable testis. lar cancer: case report and review of the literature.
Einstein (Sao Paulo). 2012;10(1):92–5.
9. Papparella A, Nino F, Coppola S, Donniacono D,
Parmeggiani P. Laparoscopy in the diagnosis and
management of splenogonadal fusion: case report.
Further Reading Eur J Pediatr Surg. 2011;21(3):203–4.
10. Putschar WGJ, Manion WC. Splenic-gonadal fusion.
1. Aweos JA, Solimane MA, Rahmane AU, Gurdiee RW. Am J Pathol. 1955;32:15–33.
Laparoscopic diagnosis and management of spleno- 11. Steinmetz AP, Rappaport A, Nikolov G, Priel IE,
gonadal fusion. Saudi Med J. 2003;1:105–6. Chamovitz DL, Dolev E. Splenogonadal fusion diag-
2. Bonneau D, Roume J, Gonzalez M, Toutain A, Carles nosed by spleen scintigraphy. J Nucl Med. 1997;38(7):
D, Maréchaud M, Biran-Mucignat V, Amati P, 1153–5.
Moraine C. Splenogonadal fusion limb defect syn- 12. Thomsen BM, Wierød FS, Rasmussen KC. Combined
drome: report of five new cases and review. Am J Med malignant testicular tumor and splenogonadal fusion. A
Genet. 1999;86(4):347–58. case story. Scand J Urol Nephrol. 1997;31(4):393–5.
3. Buccoliero AM, Messineo A, Castiglione F, Rossi 13. Velarde Ramos L, Sepulveda F, Silva E, Castillo OA.
Degl'Innocenti D, Santi R, Martin A, Taddei GL. Discontinuous intrabdominal splenogonadal fusion
Splenogonadal fusion: exceptional association with with germ cell Tumor. Excision with robotic assis-
Moebius syndrome and intestinal intussusception. tance. Adult case report. Arch Esp Urol. 2012;65(8):
Fetal Pediatr Pathol. 2011;30(4):220–4. 762–5.
Acute Scrotum
29
29.1 Introduction Common Causes of Acute Scrotum

1. Testicular torsion (16 %)
• The term acute scrotum refers to acute scrotal 2. Torsion of a testicular appendage (46 %)
pain with or without swelling and erythema. 3. Acute epididymo-orchitis (35 %)
• Acute scrotum is considered a surgical emer- 4. Idiopathic scrotal edema
gency and although there are several causes 5. Schonlein-henoch purpura
for acute scrotum, prompt differentiation 6. Incarcerated inguinal hernia
between testicular torsion and other causes of 7. Scrotal and testicular trauma
acute scrotum is critical.
• The possibility of testicular torsion and per-
manent ischemic damage to the testis must
always be kept in mind if the diagnosis is • The child with acute scrotum should be evalu-
delayed. ated rapidly both clinically and if required
• There are several causes of acute scrotum and radiologically and the possibility of torsion of
the etiology is age dependent. testis must always be kept in mind.
• Testicular torsion is commonly seen in neo- • This is important because salvaging a testis in a
nates and adolescents. child with testicular torsion is time dependent.
• Torsion of the appendix testis and acute • In doubtful cases, it is important to do an
epididymo-orchitis on the other hand are seen emergency testicular exploration rather than
most commonly in prepubertal boys. wait and loss the testis.
• The differential diagnosis of acute scrotum
include:
– Testicular torsion (16 %) 29.2 Torsion of Testes
– Torsion of a testicular appendage (46 %)
– Acute epididymo-orcitis (35 %) 29.2.1 Introduction
– Idiopathic scrotal edema
– Schönlein-Henoch purpura • Testicular torsion is the most surgical emer-
– Incarcerated inguinal hernia gency of acute scrotum as delay in diagnosis
– Scrotal trauma is known to be associated with testicular isch-
– Splenogonadal fusion emia and infarction.

602 29 Acute Scrotum
• It results from twisting of the spermatic cord • Diagnosis of testicular torsion is clinical, and
leading to venous and arterial obstruction and diagnostic testing should not delay treatment.
loss of the blood supply to the affected testis. • Approximately 32 % of pediatric torsion cases
• Early diagnosis and treatment are vital to sav- resulted in the orchiectomy.
ing the testis and preserving future fertility.
• Testicular torsion is primarily a disease of
adolescents and neonates. 29.2.2 Classification
• Neonates develop a special type of testicular
torsion which is called intrauterine testicular Testicular torsion is divided into two types
torsion. (Fig. 29.1):
• This is different from the more common tor-
sion seen in adolescent. 1. Intravaginal torsion:
– This type of torsion occurs extravaginally • Intravaginal torsion most commonly occurs
while the adolescent torsion occurs in adolescents.
intravaginally. • Intravaginal torsion constitutes approxi-
– This type of torsion commonly occurs in mately 16 % of cases in patients presenting
utero but there are reported cases occurring to an emergency department with acute
shortly after birth. scrotum.
– Intrauterine torsion is known to be associ- • This form of testicular torsion is most
ated with a high incidence of testicular commonly seen in males younger than
infarction as in the majority of reported 30 years.
cases, the testis is already necrotic at the • The peak incidence occurs at age 12–18 years.
time of exploration • The left testis is more frequently involved.
– There are however rare reports of testicular • Bilateral torsion account for 2 % of all
salvage in some of these patients. torsions.

representation of the two INTRAVAGINAL TORSION EXTRAVAGINAL TORSION
types of testicular torsion
29.2 Torsion of Testes 603
2. Extravaginal torsion (Figs. 29.2 and 29.3): – This is one reasons why contralateral
• Extravaginal torsion occurs most com- orchidopexy is important in those with
monly in neonates. unilateral intrauterine torsion.
• It accounts for approximately 5 % of all
torsions.
• The timing of occurrence of extravaginal 29.2.3 Etiology
torsion is not known exactly and it is esti-
mated that about 70 % of the cases occur 1. Intravaginal torsion:
prenatally and 30 % occur postnatally. • The exact etiology of intravaginal torsion
• Extravaginal torsion is also known to occur is not known.
in patients with high birth weight. • Normally, once the testes reaches the scro-
• Extravaginal torsion occurs most com- tum it is fixed in place by mature attach-
monly on one side and bilateral perinatal ments. This ensures firm fixation of the
torsion is extremely rare, but an increase epididymal-testicular complex posteriorly
in the number of case reports with bilat- and effectively prevents twisting of the
eral intrauterine torsion has been spermatic cord.
observed. • The tunica vaginalis is normally attached
• The occurrence of bilateral torsion can be: to the postero-lateral aspect of the
– Synchronous (occurring simultaneously) testes.
– Metachronous (occurring at different • The most accepted embryological etiology
times). of intravaginal testicular torsion is the bell
clapper deformity.
• This defect occurs in about 17 % of males
and is bilateral in 40 %.
• High abnormal attachment of the tunica
vaginalis to the testicle makes the sper-
matic cord liable to rotate within it, which
can lead to intravaginal torsion.
• In intravaginal torsion, the testis can rotate
freely on the spermatic cord within the
tunica vaginalis.
• In males with the bell-clapper deformity, tor-
sion can occur because of a lack of fixation,
resulting in the testes being freely suspended
within the tunica vaginalis (Fig. 29.4).
• The bell clapper deformity can result in the
long axis of the testicle being oriented
transversely rather than cephalocaudal.
• Another abnormality that can predispose
to intravaginal torsion is abnormal mesen-
tery between the testis and its blood
supply.
1. Extravaginal torsion:
• This occurs because the tunica vaginalis is
not yet secured to the gubernaculum and,
therefore, the spermatic cord, as well as
Figs. 29.2 and 29.3 Intraoperative photographs of two the tunica vaginalis, undergo torsion as a
newborns with extravaginal testicular torsion unit.

bell-clapper deformity.
This predisposes to
intravaginal torsion of
testis
TUNICA
VAGINALIS
EPIDIDYMIS
TESTIS
• In neonates, the testes frequently has not • The patients may describe previous episodes
yet fully descended into the scrotum, where of recurrent acute scrotal pain that has resolved
it becomes attached within the tunica spontaneously. This history is highly sugges-
vaginalis. This mobility of the testicle pre- tive of intermittent torsion and detorsion of the
disposes it to extravaginal torsion. testis. A detailed history is important in this
regard.
• Acute testicular torsion develops in 10 % of
29.2.4 Clinical Features patients with intermittent torsion while they
waite for surgery.
Intravaginal Torsion • Physical examination may reveal:
• The usual presentation of intravaginal testicu- – A swollen, tender, high-riding testis
lar torsion is a sudden onset of severe unilat- – Abnormal transverse lie of testis
eral scrotal pain followed by inguinal and/or – Loss of the cremasteric reflex
scrotal swelling. Gradual onset of pain is an – Edema involving the entire scrotum
uncommon presentation. – Enlargement and edema of the testis
• The pain may decrease in severity as the – Fever is uncommon
necrosis of testis becomes more complete. – Scrotal erythema
• Torsion of testis commonly occurs spontane- • The cremasteric reflex is almost always absent
ously but may occur during sports or physical or diminished on the affected side in patients
activity. with testicular torsion.
• Torsion of testis can also occur in association • Prehn’s sign: Relief of pain with elevation of
of trauma. This is seen in 4–8 % of the cases. the affected testis.
• Approximately one third of patients also have • Although a negative Prehn’s sign is classically
gastrointestinal upset with nausea and vomiting. thought to be a predictor of torsion, this is
• The patients rarely report voiding difficulties unreliable for diagnosis.
or painful micturition. • Factors predictive of testicular torsion include:
• In some patients, scrotal trauma or other scro- – Acute onset of testicular pain
tal disease (including torsion of appendix testis – Duration of pain of less than 6 h
or epididymitis) may precede the occurrence – Fever, nausea and vomiting
of subsequent testicular torsion. – History of trauma or physical activities
Figs. 29.5 and 29.6 Clinical photographs showing two newborns with torsion of testis. Note the enlarged scrotum in
both. Sometimes the skin is discolored and the affected testis is elevated
– Absence of cremasteric reflex

– Abnormal transverse lie of affected testis
Extravaginal Torsion
• In neonates, prenatal extravaginal torsion
presents as a hard, nontender testis that is
fixed to the overlying scrotal skin which is dis-
colored (Figs. 29.5 and 29.6).
• The affected testis is swollen.
• Unilateral absence of the testis with blind-
ending vas and vessels is thought to be a mani-
festation of early in utero torsion. This is also Fig. 29.7 A clinical intraoperative photograph showing a
supported by finding hemosiderin in the distal small atrophic testis with an intact vas suggestive of intra-
section of the spermatic cord (Fig. 29.7). uterine torsion of testis
• Acute scrotal swelling and tenderness without
fixation to the scrotal wall, may represent a 29.2.5 Effects of Torsion of Testes
postnatal torsion with some hope of subse-
quent testicular salvage with early surgical • Torsion of the testes causes venous occlusion
management. and engorgement as well as arterial ischemia
• Prenatal torsion manifests as: and subsequent infarction of the testis. The
– A firm, hard, scrotal mass extent of this depends on two factors:
– It does not transilluminate – The degree of torsion (Fig. 29.8):
– It occurs in an otherwise asymptomatic, • Torsion occurs as the testis rotates between
healthy and of good weight male newborn 90° and 180°, compromising blood flow to
– The scrotal skin characteristically fixes to and from the testis.
the necrotic gonad and the scrotum is • Incomplete or partial torsion occurs with
enlarged lesser degrees of rotation.
Fig. 29.9 A Doppler ultrasound showing torsion of the

Fig. 29.8 A clinical photograph showing a newborn with right testis
extravaginal torsion. Not the already necrotic testis
• Complete torsion usually occurs when the • The sensitivity of color Doppler examination
testis twists 360° or more. The degree of tor- in detecting acute testicular torsion in children
sion may extend to 720°. is 90–100 %, with specificity being 100 %
– The duration of torsion: (Figs. 29.10 and 29.11).
• The duration of torsion is the most • Other studies have suggested that color
important factor that influences the rates Doppler ultrasonography was only 86 % sen-
of both immediate salvage and late tes- sitive, 100 % specific, and 97 % accurate in the
ticular atrophy. diagnosis of testicular torsion.
• Testicular salvage is most likely if the • If the diagnosis is equivocal, radionuclide
duration of torsion is less than 6 h. scan of the testis can be helpful to assess blood
• If 24 h or more elapse, testicular necro- flow and to differentiate testicular torsion
sis develops in most patients. from other causes of acute scrotum.
• The cause of decreased fertility observed in • Radionuclide scans have a sensitivity of
patients with unilateral testicular torsion is not 90–100 % in detecting testicular blood
known and two factors were suggested as pos- flow.
sible theories. • If the patient does not show clinical evidence
– An inherent bilateral testicular abnormalities of testicular torsion, a urinalysis and culture
– An autoimmune mechanism affecting the may help exclude urinary tract infection and
contralateral testis. This hypothesis how- epididymitis.
ever was not supported. • The complete blood count can be normal.
However, the WBC count is elevated in as
many as 60 % of patients who have testicular
29.2.6 Investigations torsion.
• Testicular torsion is a clinical diagnosis.

• If the history and physical examination 29.2.7 Treatment
strongly suggest testicular torsion, the patient
should undergo emergency exploration with- • Surgical exploration and testicular detorsion
out delay to perform investigations and imag- is the definitive treatment for testicular
ing studies. torsion.
• When a low suspicion of testicular torsion • Manual nonsurgical detorsion of the affected
exists, color Doppler ultrasonography can be testis may be attempted but is usually difficult
used to demonstrate arterial blood flow to the because of acute testicular pain during manip-
testis and provide information about other tes- ulation. During this maneuver, the testis should
ticular pathology (Fig. 29.9). be detorted in medial to lateral direction.
Figs. 29.10 and 29.11

A Doppler ultrasound
showing epididymitis.
Note the enlarged left
epididymis and the good
blood flow to the testis
• If manual detorsion is successful based on – Retention of a necrotic testis may exacer-

complete resolution of symptoms and bate the potential for subfertility, presum-
confirmed by color Doppler ultrasound in a ably because of development of an
patient with testicular torsion, the patient autoimmune phenomenon. This however is
should undergo definitive surgical fixation of not fully supported.
both testes before leaving the hospital. The – There are others who advocate emergency
operation can be performed as an urgent rather exploration.
than an emergency procedure. • The argument in favor of this is that the
• A bilateral scrotal orchidopexy is recom- timing of testicular torsion is not exactly
mended to treat torsion of testis. This is to pre- known and although the chance of sav-
vent torsion of the other testis. ing the testis is small, this is worth
• The treatment of neonatal torsion is still doing.
controversial. • Add to this the fact that these patients
– Some advocate elective rather than emer- are usually healthy with no other abnor-
gency exploration and contralateral orchi- malities and of good size and currently
dopexy because bilateral (synchronous or the anesthesia is safe (Figs. 29.12,
asynchronous) neonatal testicular torsion 29.13, 29.14 and 29.15).
has been described. • The placement of a testicular prosthesis is
– If the testis is necrotic, an orchiectomy and usually delayed for 6 months, until healing is
contralateral orchidopexy is performed. complete and inflammatory changes resolve.
Fig. 29.12 An intraoperative photograph showing an

already necrotic testis in a newborn with testicular torsion
Figs. 29.14 and 29.15 Intraoperative photographs
showing viable testes in two newborns with intrauterine
torsion following exploration and detorsion of the testes
• There are two types of testicular

appendices:
– The appendix testis
– The epididymal appendix
• Torsion of testicular appendices is considered
the leading cause of acute scrotum in
children.
• In those with acute scrotal pain, the incidence
Fig. 29.13 An intraoperative photograph showing of torsion of testicular appendage ranges from
already necrotic testes in a newborn with bilateral intra- 46 % to 71 %.
uterine testicular torsion • Torsion of the testicular appendices is virtu-
ally a benign condition, but must be distin-
guished from testicular torsion.
29.3 Torsion of the Testicular • The appendix testis and epididymal appendix
or Epididymal Appendage are commonly pedunculated and because of
this are predisposed to torsion.
29.3.1 Introduction • Torsion of either appendage (The appendix
testis and epididymal appendix) produces
• Torsion of testicular appendices is one of the pain similar to that experienced with testicu-
most common causes of acute scrotum lar torsion, but the onset is usually more
(Fig. 29.16). gradual.

common testicular
appendages
THE VAS AND
VESSELS
THE EPIDIDYMAL
APPENDIX
THE APPENDIX
TESTIS
29.3.2 Embryology
• The appendix testis:

– This is a Müllerian duct remnant.
– It is present in 92 % of all testes.
– It is located at the superior pole of the testis
in the groove between the testis and
epididymis.
– It is the most common appendage to
undergo torsion.
• The epididymal appendix:
Fig. 29.17 An intraoperative photograph showing tor-
– This is a Wolffian duct remnant.
sion of the appendix testis
– The appendix epididymis is present in 23 %
of testes.
– It is usually located on the head of the • The pain is usually not associated with sys-
epididymis. temic symptoms such as nausea, vomiting or
– It is the second common appendage to urinary symptoms.
undergo torsion. • Usually, the scrotum appears normal but
sometimes there is an associated erythema
and edema.
29.3.3 Clinical Features • The cremasteric reflex is usually intact.
• Occasionally, a paratesticular nodule at the
• The majority (80 %) of torsion of the testicular superior aspect of the testicle is present. This
or epididymal appendage occurs in boys aged is called the blue-dot sign which is present in
7–14 years (Mean age 10.6 years). only 20 % of cases (Fig. 29.17).
• The usual presentation is acute scrotal pain
but the onset is more gradual. This is impor-
tant in distinguishing this from testicular tor- 29.3.4 Investigations and Treatment
sion which presents with sudden acute scrotal
pain. • Ultrasonography can be useful in distinguish-
• The pain is more localized to the upper pole of ing torsion of a testis and torsion of an appen-
the testis which is also tender. dix testis.
• Color Doppler ultrasonography is the imaging

modality of choice for evaluation of the acute
scrotum.
• This usually shows normal blood flow to the
testis and sometimes an increase blood flow
on the affected side due to inflammation.
• This is a self- limiting condition and most
cases are treated conservatively.
• Rarely surgery is indicated:
– If it is difficult to differentiate from testicu-
lar torsion.
– If the pain is severe and cannot be con-
trolled by analgesics.
• The management includes:
– Nonsteroidal anti-inflammatory drugs and Fig. 29.18 A clinical photograph showing a child with
analgesics. acute scrotum secondary to severe epididymo-orchitis
– Torsion of a testicular appendage may be with intrascrotal abscess formation
misdiagnosed as epididymitis but if the uri-
nalysis is normal, no antibiotic therapy is • It has been shown that 47 % of prepubertal
required. boys and 75 % of infants with epididymitis
– The inflammation usually resolves within a have an underlying urogenital anomaly.
week.
29.4.2 Etiology
29.4 Epididymitis, Orchitis,
and Epididymo-orchitis • The exact etiology of acute epididymitis is
unknown.
29.4.1 Introduction • Acute epididymitis is believed to be caused by
the retrograde passage of urine from the
• Acute epididymo-orchitis is a clinical diagno- prostatic urethra to the epididymis via the
sis consisting of pain, swelling and inflamma- ejaculatory ducts and vas deferens.
tion of the epididymis, with or without • There are however several contributing causes
inflammation of the testes. for acute epididymitis including:
• It is an important cause of acute scrotum in – Genitourinary abnormalities in infants and
children (Fig. 29.18). young boys.
• Orchitis (infection limited to the testis) is – In older boys, acute epididymitis is often
much less common and commonly caused by idiopathic.
mumps. – Epididymitis can also be secondary to sys-
• Chronic epididymitis refers to inflammation temic diseases, such as:
that lasts for more than 6 months. • Sarcoidosis.
• Epididymitis is considered the most common • Kawasaki disease.
cause of acute scrotum in older boys, and it is • Henoch-Schönlein purpura.
important to differentiate this from testicular – Inflammation of the epididymis may be
torsion. also reactive secondary to trauma or torsion
• There is an increased incidence of genito- of an appendix testis.
urinary abnormalities in prepubertal boys with – Chemical irritation from sterile reflux of
epididymitis. urine into the seminal tract.
29.4 Epididymitis, Orchitis, and Epididymo-orchitis 611
– Epididymitis in children can also be drug- • Infants and children with epididymitis have a
induced (amiodarone-induced epididymitis) high incidence of associated urogenital abnor-
• Bacterial epididymitis is caused by several malities, and thus require full urological
organisms including: evaluation.
– Coliforms, Pseudomonas species, Ureaplasma, • Renal ultrasound, a voiding cystourethrogram
Mycoplasma species, Staphylococcus, Proteus and urodynamic studies are necessary investiga-
species, and Haemophilus influenzae. tions in prepubertal boys with acute epididymi-
– In sexually active patients, Chlamydia and/ tis. This is specially so in the presence of urinary
or Neisseria gonorrhoeae may be the caus- tract infection (Figs. 29.19, 29.20 and 29.21).
ative organism.
– Viral causes include paramyxovirus, Clinical features
Coxsackie virus, echovirus, and adenovirus. Pain 96 %
– Granulomatous epididymitis is very rare in Swelling 100 %
children and can be secondary to Erythema 72 %
tuberculosis. Fever 40 %
Leucocytosis 44 %
A positive urinalysis 24 %
Lower urinary tract symptoms 16 %
29.4.3 Clinical Features (frquency, urgency, enuresis)
Nausea and vomiting 16 %
• The usual presentation is with unilateral
scrotal pain and swelling of relatively acute
onset. • In patients with signs of urinary tract infec-
• Acute epididymitis is usually unilateral but it tion, treatment includes empiric antibiotic
is bilateral in 5–10 % of the patients. therapy until the results of a urine culture are
• There may be a history of a urinary tract known.
infection. • Treatment should start with an oral or I.V
• Tenderness on the affected side. broad-spectrum antibiotic depending on the
• The epididymis will be enlarged and tender or presence or absence of signs of systemic
the whole testis and epididymis will be infection. Treatment should be continued for
tender. 10–14 days and the antibiotics modified
• There may also be erythema and/or edema of according to the culture result.
the scrotum on the affected side. • Patients with underlying genito-urinary abnor-
malities usually require surgical intervention.
• In the absence of urinary tract infection, treat-
29.4.4 Investigations and Treatment ment is supportive including:
• Urinalysis with culture and sensitivity. – Non-steroidal anti-inflammatory drugs and
• Blood culture. analgesics.
Differential diagnosis and management of the acute scrotum
Onset of Site of Cremasteric
Type symptoms Age at diagnosis tenderness Urinalysis reflex Treatment
Testicular torsion Acute Early puberty Diffused Negative Negative Surgical
exploration
Appendicealr Subacute Prepubertal Localized to Negative Positive Bed rest and
torsion upper pole scrotal
elevation
Epididymitis Insidious Adolescence Epididymal Positive or Positive Antibiotics
negative
UTRICULAR
UTRICULAR
CYST
CYST
Figs. 29.19, 29.20, and 29.21 A micturating cystourethrogram, CT-scan and an intraoperative photograph showing a
large utricular cyst in a child with recurrent epididymitis
29.5 Idiopathic Scrotal Edema • In idiopathic scrotal edema (Fig. 29.22):

– The scrotal skin is thickened, edematous,
• Acute idiopathic scrotal edema is one of the and often inflamed.
differential diagnosis in children presenting – The testis and epididymis are not tender
with an acute scrotum. and of normal size and position.
• Acute idiopathic scrotal edema was first – The affected scrotum is enlarged when
reported by Qvist in 1956. compared to the other side.
• It is characterized by scrotal edema and • It occurs less frequently than epididymitis, tes-
erythema. ticular torsion, or torsion of testicular append-
• It is a self-limiting condition. ages and is more common in boys than in adults.
29.7 Other Causes of Acute Scrotum 613
29.6 Testicular Trauma
• Testicular injury is uncommon and usually

results from either a direct blow to the scrotum
or a straddle injury.
• Traumatic damage to the testes results mostly
from forceful compression of the testis against
the pubic bones.
• Scrotal trauma can also result in intratesticular
hematoma, hematocele or laceration of the
tunica albuginea (testicular rupture).
• Color Doppler ultrasonography is the imaging
technique of choice.
• Testicular rupture requires immediate surgery
and repair.
Fig. 29.22 A clinical photograph with idiopathic scrotal
edema
29.7 Other Causes of Acute
Scrotum
• Over 75 % of cases occur in boys less than
10 years of age. • Schönlein-Henoch purpura:
• Two thirds of cases are unilateral. – A systemic vasculitis of unknown
• Idiopathic scrotal edema is characterized by: etiology.
– The rapid onset of significant edema with- – It is characterized by (Figs. 29.23 and
out tenderness. 29.24):
– Painless erythema and induration of the • Nonthrombocytopenic purpura
scrotum. • Arthralgia
– Edema and erythema may extend to the • Renal disease
phallus, groin, and lower abdomen. • Abdominal pain
– The patient is usually afebrile. • Gastrointestinal bleeding
– Patients may complain of pruritus. • Scrotal pain
– All diagnostic tests are negative. – The onset can be acute or insidious.
• The etiology of this condition remains – Hematuria may be present.
unclear. – The syndrome has no specific treatment.
• An allergic reaction is the most likely • Incarcerated inguinal hernia:
cause. – This should be suspected in a child who has
• Sonography plays an important role in exclud- a history of intermittent groin swelling.
ing testicular torsion, epididymitis, and tor- – The usual presentation is with an irreduc-
sion of a testicular appendage and confirming ible painful and tender inguinal or inguino-
the diagnosis of acute idiopathic scrotal scrotal swelling.
edema. – In those with strangulated hernia, there
• Treatment consists of bed rest and scrotal may be an associated scrotal swelling and
elevation. redness (Figs. 29.25 and 29.26).
• Analgesics are rarely needed. – This may be due to bowel congestion and
• Most cases resolve spontaneously within a ischemia or sometimes localized bowel
few days and do not require specific perforation.
treatment. – An incarcerated or strangulated hernia
• There is a 20 % recurrence rate. requires urgent surgical intervention.
Figs. 29.23 and 29.24 Clinical photographs showing a child with Schönlein-Henoch purpura. Note the skin rash
which is nonthrombocytopenic. This patient also had scrotal pain as well as abdominal pain
• Varicocele:
– Occasionally, a varicocele causes mild to
moderate scrotal discomfort.
– No changes in the scrotal skin occur, but
the affected hemi-scrotum may have a full
appearance.
– On physical examination, a varicocele is
palpable as a “bag of worms” above a nor-
mal testis and epididymis (Fig. 29.29).
29.8 Splenogonadal Fusion
• Splenogonadal fusion is a rare congenital mal-

formation that results from an abnormal fusion
between the primitive spleen and gonad.
• Splenogonadal fusion is a rare, benign, con-
genital anomaly thought to occur between the
fifth and eighth weeks of intrauterine life
Figs. 29.25 and 29.26 A clinical and intraoperative where immature splenic tissue adheres to the
photographs of a child who presented with a strangulated developing gonad, epididymis or vas
right inguinal hernia. Note the associated scrotal swelling, deferens.
and redness secondary to intestinal ischemia • The splenic tissue is subsequently pulled in a
caudal direction with descent of the gonad.
• Hydrocele: • Karaman and Gonzales in 1996 reviewed 137
– A hydrocele occurs because of a patent cases of splenogonadal fusion and surpris-
processus vaginalis. ingly 37 % of the patients had orchiectomy
– Most hydroceles resolve spontaneously. because of suspicion of a testicular tumor.
– The usual presentation is that of a scrotal • This is of great importance and to obviate
swelling that transilluminate and usually this physicians caring for these patients
does not cause pain (Figs. 29.27 and should be aware of this and intra-operatively
29.28). if there is doubt concerning the nature of the
29.8 Splenogonadal Fusion 615
Figs. 29.27 and 29.28 Clinical photographs showing hydroceles in a child. This usually present with a scrotal swell-
ing that is not painful
– The number of cases reported in patients

<20 years old account for 70 %.
• Splenogonadal fusion is commonly asymp-
tomatic discovered incidentally during routine
herniotomy or orchidopexy.
• Splenogonadal fusion may presents as an
asymptomatic testicular mass.
VARICOCELE
• Many of these cases however go passed unno-
ticed or discovered at autopsy.
• Other manifestations may include acute tes-
ticular pain and swelling caused by ectopic
splenic tissue infections.
Fig. 29.29 A clinical photograph showing a left
varicocele • In the pediatric age group, these patients com-
monly present with a scrotal swelling and may
rarely present with an acute scrotal pain as a
swelling, intra-operative frozen section result of torsion or involvement of splenic
biopsy should be performed to avoid unnec- tissue with other pathological conditions such
essary orchiectomy. as mumps, malaria, leukemia, trauma and
• Splenogonadal fusion occurs more commonly infectious mononucleosis.
in males with a male-to-female ratio of 15:1. • Not uncommonly splenogonadal fusion is
This figure may of course be inaccurate due to associated with other anomalies or discovered
the relative inaccessibility of the ovary to clin- during the evaluation of these associated
ical examination. anomalies. This is more so with the continu-
• It is seen nearly always on the left side. ous type which is known to be associated with
• Splenogonadal fusion is common in children other associated anomalies in as much as 33 %
and adolescents. of the cases.
– The number of cases reported in patients • There are two types of splenogonadal fusion:
<10 years of age account for 50 % of the – Continuous
total cases reported. – Discontinuous
separated from the normal spleen

(Fig. 29.30 ).
• Both types occur with equal frequency and the
discontinuous type may be discovered inci-
dentally during herniotomy or orchidopexy or
present as a scrotal swelling. Awareness of
this is of great importance to avoid unneces-
sary orchiectomy mistaken it for a testicular
tumor.
Fig. 29.30 A clinical intraoperative photograph of sple-
nogonadal fusion diagnosed in a child with unusual tes-
• Treatment is surgical excision and every
ticular swelling attempt should be made to preserve the gonad
at the time of dissection and excision which
should not be difficult since true fusion with
• In continuous splenogonadal fusion there the gonad is rare.
remains a connection between the main spleen • Although there have been few reports of an
and gonad. association of testicular neoplasms with sple-
• In discontinuous splenogonadal fusion, ecto- nogonadal fusion, it appears that this is a coin-
pic splenic tissue is attached to the gonad, but cidental finding rather than an association as
there is no connection to the main spleen. these tumors occurred in adults with unde-
• The continuous form occurs when the nor- scended testes.
mally located spleen is attached to the gonad • The diagnosis of splenogonadal fusion should
by a discrete cord. always be kept in mind and included in the dif-
• In the discontinuous type the splenic tissue ferential diagnosis of testicular swelling in
is attached to the gonad and completely infants and children.
Further Reading 617
ACUTE SCROTUM
HISTORY AND PHYSICAL

EXAMINATION
SHORT DURATION OF LONG DURATION OF

SYMPTOMS AND HIGHLY SYMPTOMS AND NOT
SUGGESTIVE OF HIGHLY SUGGESTIVE OF
TESTICULAR TORSION TESTICULAR TORSION
EMERGENCY URINE ANALYSIS AND COLOR

SURGICAL DOPPLER ULTRASONOGRAPHY
EXPLORATION
INCREASED OR NORMAL
DECREASED OR ABSENT BLOOD FLOW AND
BLOOD FLOW OR POSITIVE URINE
EQUIVOCAL RESULT
TREAT AS
INCREASED OR NORMAL BLOOD EPIDIDMO-ORCHITIS
FLOW AND NEGATIVE URINE
NON-OPERATIVE MANAGEMENT
OR OBSERVATION
retrospective study of 172 boys. Pediatr Radiol.

Further Reading 2005;35(3):302–10.
4. Kass EJ, Lundak B. The acute scrotum. Pediatr Clin
1. Boettcher M, Bergholz R, Krebs TF, Wenke K, North Am. 1997;44:1251.
Aronson DC. Clinical predictors of testicular torsion 5. Schalamon J, Ainoedhofer H, Schleef J, et al.
in children. Urology. 2012;79(3):670–4. Management of acute scrotum in children – the
2. Dajusta DG, Granberg CF, Villanueva C, Baker impact of Doppler ultrasound. J Pediatr Surg.
LA. Contemporary review of testicular torsion: new 2006;41:1377.
concepts, emerging technologies and potential thera- 6. Yang Jr C, Song B, Liu X, Wei GH, Lin T, He
peutics. J Pediatr Urol. 2013;9(6 Pt A):723–30. DW. Acute scrotum in children: an 18-year retro-
3. Karmazyn B, Steinberg R, Kornreich L. Clinical and spective study. Pediatr Emerg Care. 2011;27(4):
sonographic criteria of acute scrotum in children: a 270–4.
Hydrocolpos, Vaginal Agenesis
and Atresia 30
30.1 Introduction opening which completely obstructs the

vagina (Fig. 30.1).
• Hydrocolpos is the distension of the vagina • It is caused by a failure of the hymen to perfo-
caused by accumulation of fluid due to con- rate during fetal development.
genital vaginal obstruction. • It is most often diagnosed in adolescent girls
• The obstruction is often caused by an imperfo- when menstrual blood accumulates in the
rate hymen or less commonly a transverse vagina (hematocolpos) and sometimes also in
vaginal septum. the uterus.
• The fluid consists of cervical and endometrial • In adolescent females:
mucus. – The most common symptoms of an imper-
• In rare instances the hydrocolpos is secondary forate hymen are cyclic pelvic pain and
to urine accumulated through a vesicovaginal amenorrhea.
fistula proximal to the obstruction or due to – The cyclic pain is secondary to hematocolpos.
the presence of urogenital sinus with collec- – Other symptoms include urinary retention,
tion of urine. constipation, back pain, nausea, and diarrhea.
• The term hydrometrocolpos is when hydro-
colpos is associated with fluid accumulation
in the uterus.
• Vaginal atresia is a congenital abnormality of
the female genital system.
• It represent a spectrum of malformations rang-
ing from total vaginal agenesis to vaginal
atresia.
30.2 Imperforate Hymen
• Imperforate hymen is the most common and

most distal form of vaginal outflow
obstruction.
• An imperforate hymen is a congenital malfor- Fig. 30.1 A clinical photograph showing a newborn with
mation characterized by a hymen without an imperforate hymen. Note the bulging hymenal membrane

620 30 Hydrocolpos, Vaginal Agenesis and Atresia
Figs. 30.2 and 30.3 Clinical photographs showing a newborn with imperforate hymen. Note the whitish bulging
hymenal membrane
• The hymen originates from the embryonic • Imperforate hymen is the most frequent cause
vagina buds from the urogenital sinus. of vaginal outflow obstruction, occurring in
• As a consequence, the hymen is a composite 0.1 % of infant girls.
of vaginal epithelium and epithelium of the • This vaginal outlet obstruction results in the
urogenital sinus interposed by mesoderm. entrapment of vaginal and uterine secretions
• Once the hymen becomes perforated or forms under the influence of maternal estrogens and
a central canal, it establishes a communication this becomes evident when the distensible
between the upper vaginal tract and the vesti- membrane bulges between the labia.
bule of the vagina. • In adolescence, the retained secretions consist
• Normally, there are anatomic variations of the of menstrual products, and the resulting mass
patent hymen. effect in the vagina and uterus are referred to
– The most common being an annular or cir- as hematocolpos and hematometrocolpos,
cumferential hymen in which the hymen respectively.
completely surrounds the vaginal orifice • Pyocolpos (infection of a hydrocolpos) may
and has a central opening. result from an infection that is ascending
– Other appearances of the hymen include through microperforations in the hymen
crescentic, fimbriated, septate, cribriform, membrane.
and microperforate forms. • Clinical presentations of imperforate hymen
• It is proposed that an imperforate hymen is in newborns include:
formed during fetal development when the – An incidental finding on routine physical
sinovaginal bulbs fail to canalize with the rest examination of a newborn.
of the vagina. This result is a solid membrane – The neonate with imperforate hymen typi-
interposed between the proximal uterovaginal cally presents with a bulging membrane
tract and the introitus. between the labia.
• The exact cause of imperforate hymen is not – The membrane may be white or yellow-grey
known. because it is distended from trapped mucoid
• Imperforate hymen may result from failure of material secreted as a result of stimulation by
apoptosis due to a genetically transmitted sig- maternal estrogen (Figs. 30.2 and 30.3).
nal, or it may be related to an inappropriate – In severe cases, the distention extends prox-
hormonal milieu. imally into the uterus (hydrometrocolpos).
• Familial inheritance in successive generations – A lower abdominal midline mass may be
has been described evident on physical examination because
beyond the neonatal period, the optimal time

for surgical repair is after the onset of puberty
and prior to menarche.
30.3 Vaginal Atresia
• This is a birth defect where the vagina is

blocked off to varying degrees.
• It is often associated with syndromes such as:
– Bardet-Biedl syndrome
– Fraser syndrome
– Mayer-Rokitansky-Küstner-Hauser (MRKH)
syndrome
• Mayer-Rokitansky-Küstner-Hauser (MRKH)
syndrome: This syndrome is characterized by
the followings:
– Absent uterus
– A deformed or absent vagina
– Normal ovaries
– Normal external genitalia.
• Vaginal atresia is estimated to occur in 1 in
5,000–10,000 live female births.
• Vaginal atresia is a congenital developmental
Fig. 30.4 A clinical photograph showing labial adhesions defect resulting in uterovaginal outflow
(fused labia) not to be confused with imperforate hymen obstruction which can present either:
– In the neonatal period with hydrocolpos as
a result of accumulation of secretions from
the shallow pelvis of a neonate allows the the normal cervical glands under the influ-
uterus to be palpated above the pubis ence of maternal hormones. Extension of
symphysis. fluid accumulation to involve the uterus
– Hydrocolpos can lead to urinary tract infec- will result in hydrometrocolpos.
tions or bladder obstruction and acute uri- – Hydrocolpos can be complicated by infec-
nary retention. tion leading to pyocolpos.
• Asymptomatic imperforate hymen should not – In adolescence with hematocolpos as a
be confused with labial adhesions (fused result of obstruction to the normal menstrual
labia) (Fig. 30.4) flow or with primary amenorrhea. Vaginal
• The diagnosis is made clinically and can be atresia is reported to be the second most
confirmed by ultrasonography. common cause of primary amenorrhea.
• The treatment is hymenotomy in those with
evidence of obstruction or urinary symptoms.
• Others advocate observation throughout child- 30.4 Classification
hood, with a planned hymenotomy after the
onset of puberty. • Vaginal atresia is classified anatomically into
• If a patient is diagnosed with an asymptomatic three types:
imperforate hymen in infancy or childhood – Vaginal agenesis
• Mayer-Rokitansky-Küster-Hauser – The two müllerian ducts proceed caudad to

(MRKH) syndrome cephalad and fuse together to form the
– Proximal vaginal atresia uterine cavity and upper two thirds of the
– Distal vaginal atresia vagina.
– The fallopian tubes are formed from the
cephalic remnants of the müllerian duct.
30.5 Associated Anomalies – The sinovaginal bulbs form as bilateral
endodermal invaginations.
• Vagina atresia and agenesis are congenital – Cephalic growth of the sinovaginal bulb
anomalies of the female genitourinary tract and their fusion with the vaginal cord forms
and may occur as: the vaginal plate.
• An isolated developmental defect – Canalization of the uterovaginal canal is
• Part of a complex of developmental anomalies believed to occur from the caudal to the
such as: cephalic aspect, with an epithelial lining
– The Rokitansky-Mayer-Küster-Hauser derived from the urogenital sinus.
(RMKH) syndrome – Vaginal development is completed by
– The Bardet-Biedl syndrome 5 months’ gestation and their musculature
– The Kaufman-McKusick syndrome is derived from surrounding mesenchyme.
– The Fraser syndrome – The vagina is embryologically derived
– The Winters syndrome. from both the müllerian ducts and the uro-
• Renal anomalies: genital sinus.
– Occur in 30 % of patients with RMKH – It is postulated that the upper two thirds of
syndrome. the vagina are derived from the mullerian
– These anomalies include: ducts and the lower third is derived from
• Unilateral agenesis of the kidney the urogenital sinus.
• Ectopic kidneys • Failure of this normal development at any
• Horseshoe kidney stage can lead to genital abnormalites:
• Crossed-fused renal ectopia – Persistent Mullerian duct syndrome: This
• Skeletal anomalies: is seen in male children as a result of fail-
– Fused vertebrae ure of secretion of MIS or failure of the
– Anomalies of the ribs and limbs receptors to respond to MIS. It is character-
ized by the presence of a uterus, upper part
of vagina and fallopian tubes in a pheno-
30.6 Embryology typically and genetically normal male.
– A septate uterus: This results from failure
• Normally there are two pairs of ducts in the of the septum between the two mullerian
embryo, the wollfian and Mullerian ducts. ducts to regress.
• These are responsible for the development of – Arcuate, bicornuate, or didelphic uteri:
the male (Wollfian) and female (Mullerian) These result from incomplete fusion of the
internal genitalia. müllerian ducts.
• In the female embryo: – Uterovaginal atresia: This results from fail-
– The absence of testes which secret testest- ure of the caudal development of the mül-
erone and Mullerian inhibiting substance lerian ducts.
(MIS) allow development and differentia- – A transverse vaginal septum: This results
tion of the müllerian duct system and from failures at the level of the vaginal
regression of the wolffian ducts. plate.
– The müllerian duct elongate and reaches – Vaginal atresia: This occurs when the cau-
the urogenital sinus by 9 weeks’ gestation, dal portion of the vagina, contributed by
and form the uterovaginal canal. the urogenital sinus, fails to form. This cau-
dal portion of the vagina is replaced with

fibrous tissue.
– Lower vaginal atresia is a type of vagina
atresia where the lower 3rd of the vagina
fails to develop.
– It is usually not considered a type of Mullerian
duct anomaly. It occurs from a failure of reca-
nalisation of the urogenital sinus.
– Patients with RMKH syndrome and vagi-
nal atresia are phenotypically and geno-
typically female with a 46, XX karyotype.
However, a familial association suggests Fig. 30.5 A clinical photograph showing a newborn with
abdominal mass secondary to hydrometrocolpos
autosomal dominant transmission of a
mutant gene by male relatives.
– Mayer-Rokitansky-Küster-Hauser (MRKH)
syndrome is defined as Müllerian aplasia
with vaginal agenesis and uterine remnants.
– It is commonly associated with renal and
sometimes vertebral anomalies. The
MRKH syndrome or distal vaginal atresia
is sometimes associated with anorectal
malformations.
• The clinical presentation of vaginal atresia is

Fig. 30.6 A clinical photograph showing a newborn with
variable. abdominal mass secondary to hydrometrocolpos. The
• The majority of neonates with vaginal atresia mass is arising from the pelvis upwards
are asymptomatic but they my present with:
– An abdominal mass (Figs. 30.5 and 30.6):
• This is secondary to hydrocolpos or syndrome (McKusick-Kaufman syndrome,
hydrometrocolpos. Bardet-Biedl syndrome). The polydactly can
• It may be discovered during routine affect either lower and upper limbs or only
antenatal ultrasound one limb (Figs. 30.7, 30.8, 30.9, and 30.10).
• This may be discovered clinically • Perineal examination may reveal:
immediately after delivery or during the – Normal external genitalia
first few weeks of life. – No apparent vaginal orifice and no hymen
– Sepsis – Development of secondary sex characteris-
– Respiratory distress. tics in the adolescent.
• Vaginal atresia may remain asymptomatic till – An isolated vaginal dimple or a small vaginal
adolescence and the presentation may include: pouch with a normal hymenal ring may be seen.
– Amenorrhea – Abnormal anal opening (Figs. 30.11 and 30.12)
– Cyclical abdominal pain – Labial fusion may obscure the anatomy of
– Difficulty in voiding some patients and be confused with vaginal
– An abdominopelvic mass atresia.
– Backache – The presence of posterior labial fusion and
• The presence of polydactly and congenital enlarged clitoris is suggestive of congenital
heart disease is suggestive of an associated adrenal hyperplasia.
Figs. 30.7, 30.8, 30.9, and 30.10 Clinical photographs showing polydactly both upper and lower limbs
Figs. 30.11 and 30.12 Clinical photographs showing a newborn with vaginal atresia. Note the absence of a vaginal
opening. Note also the anteriorly placed anus in the first picture
• McKusick-Kaufman syndrome: • Vaginal atresia

– This is an autosomal recessive disorder. • Other malformations of the genitalia
– It is characterized by: including micropenis, and cryptorchidism
• Hydrometrocolpos secondary to vaginal in males and clitoromegaly in females.
atresia. • Congenital malformations of the nose,
• Postaxial polydactyly ears, larynx and renal system.
• Imperforated anus • Mental retardation
• Congenital heart defects. • Syndactly
• Bardet-Biedl syndrome: • Winters syndrome:
– This is an autosomal recessive disorders. – It is characterized by ear anomalies
– It is characterized by: and vaginal atresia.
• Vaginal atresia
• Retinal dystrophy or retinitis pigmentosa
• Postaxial polydactyly
• Obesity 30.8 Investigations
• Nephropathy
• Mental disturbances • In newborns, it is important to define preop-
• Fraser syndrome: eratively the anatomic abnormality leading to
– Fraser syndrome (also known as Meyer- the hydrometrocolpos.
Schwickerath’s syndrome, Fraser-François • Whereas imperforate hymen is clinically evi-
syndrome, or Ullrich-Feichtiger syndrome) is dent and simple to treat, vaginal atresia is
an autosomal recessive congenital disorder. more complex to define and manage.
– It is characterized by: • Abdominal radiograph (Figs. 30.13 and 30.14):
• Cryptophthalmos (where the eyelids fail – This may reveal a soft tissue density push-
to separate in each eye) ing the bowel to the side and upwards.
Figs. 30.13 and 30.14 Abdominal x-rays showing a soft tissue mass representing the dilated vagina and pushing the
bowel upwards
Fig. 30.16 Abdominal CT-scan showing a very large

Fig. 30.15 Abdominal ultrasound showing a dilated
hydrocolpos
vagina (hydrocolpos) secondary to vaginal atresia
Figs. 30.17 and

30.18 Abdominal
CT-scan showing
hydrometrocolpos
secondary to vaginal
atresia DILATED
UTERUS
DILATED
VAGINA
DILATED
UTERUS
DILATED
VAGINA
• Abdominal and pelvic ultrasonography – The presence of hydrocolpos or hydrometro-

(Fig. 30.15): colpos can be detected easily with ultrasound.
– This is a simple, non-invasive investigation – It is also useful to evaluate the kidneys, ureter
for patients with suspected vaginal atresia. and urinary bladder and associated anomalies.
– It is valuable to define the ovaries, uterus, • Abdominal and pelvic CT-scan (Figs. 30.16,
and proximal vagina. 30.17, 30.18, 30.19, and 30.20):
Figs. 30.19 and 30.20 Abdominal CT-scan showing

hydronephrosis secondary to pressure from the dilated Fig. 30.21 Intravenous urography showing dilated ure-
vagina ters and hydronephrosis secondary to pressure from
hydrometrocolpos
– This gives more detailed information

regarding the anatomy and etiology.
• Intravenous urography is rarely used (Fig.
30.21).
• MRI (Figs. 30.22, 30.23, and 30.24):
– This has been reported to be more valuable
than ultrasound and CT-scan in delineating
the vaginal anatomical defect and the asso-
ciated hydroureter and hydronephrosis.
• Genitography is an unnecessary invasive
investigation that may be harmful leading to
secondary infection with subsequent pyome-
trocolpos (Figs. 30.25 and 30.26).
• This must be kept in mind when evaluating
hydrometrocolpos as there is a possibility of
secondary infection and development of pyo-
metrocolpos which is a serious complication.
• Laparoscopy may be necessary to evaluate the
uterus and adnexal structures if they are not Fig. 30.22 Abdominal MRI showing a very large
clearly identified on ultrasound, CT-scan or MRI. hydrocolpos
Figs. 30.23 and

30.24 Abdominal DILATED UTERUS DILATED VAGINA DILATED VAGINA
MRI showing
hydrometrocolpos
secondary to vaginal
atresia
COMPRESSED DILATED URINARY

RECTUM VAGINA BLADDER
URINARY DILATED
BLADDE VAGINA
Figs. 30.25 and 30.26 Contrast study showing massive extend into the uterus causing hydrometrocolpos and
hydrocolpos compressing the colon posteriorly and the sometimes spills into the peritoneal cavity via the
urinary bladder anteriorly. The accumulated fluid can Fallopian tubes
30.9 Management • The timing of surgery depends on the patient’s

presentation.
• The goals of surgical management in patients • In newborns with hydrocolpos, emergency
with vaginal atresia are: drainage of the hydrocolpos should be done or
– To relieve vaginal obstruction more preferably, an abdominoperineal vaginal
– To restore normal anatomy and a normal sex life pull-through can be done as a single stage
– To preserve the patient’s reproductive potential (Figs. 30.25, 30.26, 30.27, 30.28, 30.29,
30.9 Management 629
Figs. 30.27 and

30.28 Clinical
intra-operative
photographs showing
hydrometrocolpos DILATED
secondary to vaginal UTERUS
atresia
DILATED
VAGINA
DILATED
VAGINA
DILATED
UTERUS
FALLOPIAN
TUBES
– The distended vagina is opened anteriorly

URETHRAL OPENING
and emptied.
– A new vaginal opening is created in the
NO VAGINAL OPENING
perineum using a semicircular or trans-
verse incision at the hymenal ring.
– Using blunt and sharp dissection from
below toward the peritoneal cavity, a chan-
nel is created.
Fig. 30.29 A clinical photograph showing a newborn girl
– At this stage, it is important to protect the
with vaginal atresia. Note the Foley’s catheter in the ure-
thra. Note also the absence of vaginal opening rectum.
– A Hegar dilator is passed into the distended
vagina and the posterior wall is pushed
30.30, 30.31, 30.32, 30.33, 30.34, 30.35, downwards till the newly created vaginal
30.36, 30.37, 30.38, and 30.39): opening,
– A Foley’s catheter is inserted. – The vaginal wall is grasped with a bab-
– Laparotomy is done through a lower trans- cock, opened and a single-layer anasto-
verse abdominal incision. mosis is created between the edges and
– The hydrmetrocolpos is defined and the the hymenal regions by using absorbable
anatomy is outlined. sutures.
NEW VAGINAL
OPENING
NEW VAGINAL
OPENING
Figs. 30.30 and 30.31 Clinical intra-operative photographs showing vagina atresia and abdominoperineal vaginal
pull through. Note the new vaginal opening
Fig. 30.32 Diagram-

of vaginal atresia
URETHRAL
OPENING
VAGINAL
ATRESIA
DISTENDED
ANAL VAGINA
OPENING
URETHRAL
OPENING
VAGINAL
ATRESIA
DISTENDED
Fig. 30.33 Diagram- ANAL
VAGINA
matic representation of OPENING
vaginal atresia. Note the
markedly distended
vagina and the distance
to the perineum
30.9 Management 631
Figs. 30.34 and 30.35 Diagrammatic photograph showing the site of incision and the finger in the dilated already
opened vagina. A hegar dilator can be used as a guide
• In those without hydrocolpos, vaginal recon- • This segment is divided, and the colon
struction is delayed till late childhood or early continuity is restored by primary end to
adolesence. end anastomosis.
• In those with vaginal agenesis, there are sev- • The proximal end of the segment is
eral reconstruction procedures to create a new closed in two layers.
vagina by using either extra-abdominal tissues • A new vaginal opening is created in the
or intra-abdominal tissues. perineum using a circular or cruciate
• There is however, no consensus regarding incision at the hymenal ring.
the ideal method for creating a functional • Using blunt and sharp dissection from
vagina: below toward the peritoneal cavity, a
– The Abbe-McIndoe operation. With this channel is created through which the
procedure, a split-thickness skin graft is sigmoid segment is passed.
taken from the buttock and used to create • The sigmoid colon segment can be passed
the neovagina. in an isoperistaltic or reverse peristaleisis
– Musculocutaneous flaps using the rectus depending on the vascular supply and
and gracilis muscles are now rarely used to length of the mesenteric pedicle.
create the neovagina. • A single-layer anastomosis is created to
– Vulvovaginoplasty using tissue expanders. the hymenal regions by using absorb-
– Intestinal segments, typically derived from able sutures.
the sigmoid colon and rarely the ileum, • Attempts are made to extraperitonealize
cecum, and rectosigmoid colon. the sigmoid colon segment.
• A segment of the sigmoid colon is cho- • A Vaseline pack is placed in the neova-
sen, with a major vascular pedicle sup- gina to maintain apposition to the dis-
plying the mesenteric arcade. sected tissues.
URETHRAL
OPENING
NEW VAGINAL
OPENING
ANAL
OPENING
Figs. 30.36, 30.37, 30.38, and 30.39 Diagrammatic peritoneal cavity. The vaginal wall is pulled through this
photographs showing the perineal stage of the vagino- opening, opened and sutured to the margins. Note the
plasty and the incision used to create the opening to the finally constructed vaginal opening
Further Reading 633
• This procedure is known to be associ- Bardet-Biedl and McKusick-Kaufman syndromes.

J Med Genet. 1999;36(8):599–603.
ated with complications, mainly excess
2. Nazir Z, Rizvi RM, Qureshi RN. Congenital vaginal
mucous drainage and the potential for obstructions: varied presentation and outcome. Pediatr
prolapse. Surg Int. 2006;22(9):749–53.
– Laparoscopic Vecchietti procedure. This 3. Rajimwale A, Furness PD, Brant WO, Kyle
MA. Vaginal construction using sigmoid colon in chil-
procedure uses an acrylic olive that is placed
dren and young adults. BJU Int. 2004;94(1):115–9.
against the vaginal dimple, traction is applied 4. Slavotinek AM, Biesecker LG. Phenotypic overlap of
to the olive using an attraction device. McKusick-Kaufman syndrome with bardet-biedl syn-
drome: a literature review. Am J Med Genet. 2000;95:
208–15.
5. Wesley JR, Coran AG. Intestinal vaginoplasty for con-
Further Reading genital absence of the vagina. J Pediatr Surg. 1992;
27(7):885–9.
1. David A, Bitoun P, Lacombe D, et al. Hydrometrocolpos 6. Wester T, Tovar JA, Rintala RJ. Vaginal agenesis or
and polydactyly: a common neonatal presentation of distal vaginal atresia associated with anorectal malfor-
mations. J Pediatr Surg. 2012;47(3):571–6.
Disorders of Sexual Development
31
31.1 Introduction • It is also important to understand the psycho-

logical and social implications of gender
• The birth of a new baby is one of the most assignment in some of these patients.
dramatic events in a family, and the first ques- • In the past several names such as intersex or
tion is usually “is it a boy or a girl?” ambiguous genitalia were used to describe
• When a child is born with ambiguous external geni- disorders of sexual development but they were
talia it often comes as a surprise for the parents and not accurately descriptive.
diagnostic dilemma for the treating physicians. • Intersex (Figs. 31.1, 31.2, 31.3, 31.4, 31.5,
• It is also considered as an endocrine emer- 31.6, and 31.7):
gency situation presenting a problem of sex – Intersex literally means that the body is
assignment. between the two sexes, male and female.
• It is important for clinicians to promptly make – This is a term that is no longer used; it has
an accurate diagnosis and counsel parents on now been replaced by disorders of sexual
therapeutic options. development (DSD).
Figs. 31.1 and

31.2 Clinical
photographs showing
severe hypospadias with
abnormal genitalia

636 31 Disorders of Sexual Development
• In the past the term “hermaphrodite” was could be perceived to be pejorative by some
sometimes erroneously used to describe peo- affected families.
ple with intersex/DSD conditions. The term • All these were replaced by the term Disorders
hermaphroditism, was used after the Greek of Sexual Development (DSD).
god of sexuality Hermes and the goddess of • This was coined by International Consensus
love and sexuality, Aphrodite. The correct Conference on Intersex organized by the
technical definition of a hermaphrodite is a Lawson Wilkins Pediatric Endocrine Society
single organism that has complete sets of both and the European Society for Pediatric
male and female sexual organs. This term is Endocrinology in 2006.
also no longer used to describe humans. • It replaces the earlier terms Intersex and
• The nomenclatures such as ‘intersex’, ‘her- ambiguous genitalia which were controversial
maphrodite’, and ‘pseudohermaphrodite’ are and associated with a lot of social stigma and
no longer used. They are confusing terms and confusion.
• Disorders of sex development (DSD) are
defined as congenital conditions in which
development of chromosomal, gonadal, or
anatomical sex is atypical.
• The use of the term disorder of sex develop-
ment (DSD) is controversial among many
activists and community organizations.
• Although there are potential criticisms to the
new nomenclature, the DSD terminology has
been generally accepted and is now popularly
used in the literature.
• The medical term disorders of sex develop-
ment (DSDs) is used to describe individuals
with an atypical composition of chromosomal,
Fig. 31.3 A clinical photograph of a patient with gonadal and phenotypic sex, which leads to
DSD. It is difficult to decide whether this is a true male differences in the development of the urogeni-
or not. This patient was investigated and found to have tal tract and reproductive system.
severe virilization secondary to congenital adrenal
hyperplasia leading to enlargement of the clitoris resem- • The term DSD has a comprehensive definition
bling a male penis including any problem noted at birth in which
Figs. 31.4 and

31.5 Clinical
photographs of two new
born with cloacal
exstrophy. Note there are
no clear external
genitalia and these
patients need further
evaluation prior to sex
assignment. The external
genitalia in these
patients are usually
small and not well
developed
the genitalia are atypical in relation to the chro-

mosomes or gonads. The karyotype is used as a
prefix defining the classification of DSD.
• The newly proposed terminology and classifi-
cations have eliminated some confusion for
both the patient and the family, as well as for
health professionals.
• DSDs are rare and complex.
• It is estimated that the overall incidence of
DSDs is 1 in 4,500–5,500 live births.
• Congenital adrenal hyperplasia (CAH) and
mixed gonadal dysgenesis are the most com-
mon causes of ambiguous genitalia, constitut-
ing approximately over 50 % of all cases of
Fig. 31.6 Clinical photograph of a newborn with imper-
forated hymen with hydrocolpos causing abnormalities of genital ambiguity in the newborn period
external genitalia (Figs. 31.8 and 31.9).
• The incidence of CAH and mixed gonadal dys-
genesis is 1:15,000 and 1:10,000, respectively.
• Currently, many countries screen newborns
for CAH by use of filter-paper blood spot
17-hydroxyprogesterone measurements.
• Disorders of sexual development includes a
variety of conditions in which the reproduc-
tive system or the external genitalia are not
normal for a female or male.
• There are three general descriptive terms to
describe the sex of a person:
– Genotypic sex (Chromosomal sex): This
Fig. 31.7 A clinical photograph showing abnormal refers to the sex based on the number of sex
external genitalis. This female patient was found to have a
dermoid cyst over the clitoris causing abnormaliities of chromosomes. This depends on the pres-
the external genitalia ence of 46,XX or 46,XY chormosomes.
Figs. 31.8 and 31.9 Clinical photographs showing two patients with congenital adrenal hyperplasia. Note the abnor-
mal external genitalia which show severe virilization
– Anatomical sex (Gonadal sex): This refers – Most children with CAH think of them-
to the sex according to the gonadal differ- selves as girls.
entiation. This depends on the presence of – CAH when it occurs in males (XY chromo-
a uterus, ovaries and tubes or testes, epi- somes), the result is over-masculinization
didymis, seminal vesicles, ejaculatory and premature puberty.
ducts and prostate. • Mixed gonadal dysgenesis (MGD) is the sec-
– Phenotypic sex: This refers to the sex based ond most common cause of DSDs.
on the external anatomy of the genitalia. • Another common DSD is Androgen
This results from the differentiation of the Insensitivity Syndrome (AIS).
external genitalia under the influence of – This occurs in males (XY chromosomes)
sex-determining genes and hormones. who do not respond to testosterone
• Abnormalities in any of these result in a range normally.
of conditions that lead to abnormal develop- – This results in a feminine appearance.
ment of the sex organs and genitalia (Disorders – There are two types, complete and partial.
of sex development). – In Complete Androgen Insensitivity
• Children with DSD often have both male and Syndrome (CAIS) the result is a totally
female characteristics internally as well as feminine appearance, including typical
externally. female breast development.
• Gender identity: – Diagnosis in 46,XY phenotypic females
– This refers to the individual’s perception with complete androgen insensitivity
about his/her own gender. In some usually occurs after puberty during an eval-
individuals, gender identity is different uation for primary amenorrhea.
from the phenotypic sex. – In the Partial Androgen Insensitivity
• When a child is born with DSD, the gender Syndrome (PAIS), the genitals can vary
may not be obvious. from mostly female to almost completely
• The development of sex organs and external male.
genitalia is a very complex process that starts • One of the more unusual DSDs is 5-Alpha
at around 7–8 weeks of pregnancy in the Reductase Deficiency (5ARD), popularly
developing fetus and is complete by 12 weeks. known as “Penis at 12.”
• Great advances have been made over recent – It is caused by a deficiency of the enzyme
years in understanding the genetics and 5-Alpha Reductase which converts testest-
pathology of DSD. erone to dihydrotestesterone in males
• The Chicago Consensus new nomenclature is (XY).
based on the primary genetic defect. – Dihyrotestesterone is responsible for the
• It includes three broad categories: development of the male external
1. Sex chromosome DSD genitalia.
2. 46, XX DSD • The classic presentation of MIS (Mullerian
3. 46, XY DSD inhibiting substance) deficiency is a boy with
• The most common DSD is Congenital Adrenal a hernia on one side and an impalpable contra-
Hyperplasia (CAH). lateral gonad. At the time of surgery, a uterus
– This results in a female (XX chromosomes) and fallopian tubes are noted along with nor-
having genitals that look somewhat mal Wolffian structures.
masculine. • Clinicians should suspect the possibility of a
– In mild cases, CAH results in a slightly DSD in patients with both hypospadias and
enlarged clitoris. cryptorchidism.
– In more severe cases it can be difficult to • Infants born with ambiguous genitalia repre-
decide whether a baby is male or female. sent a true medical and social emergency.
31.2 Embryology 639
• The management of patients with DSD has – The indifferent gonads and in the absence
also changed over the years. of a Y chromosome begins to develop into
• In the past, corrective surgeries were often ovaries.
performed in infancy, but in recent years the • Thereafter, gonadal differentiation and func-
tendency has been to postpone surgery until tion determine the final phenotype.
the child has expressed a clear gender pref- • Many genes are involved in normal sexual
erence and is old enough to participate differentiation.
actively in decisions about his/her medical – The sex-determining region on the Y chro-
treatment. mosome (SRY) initiates the development
• The optimal management of patients with DSD of the indifferent gonads into testes.
must be individualized and multidisciplinary, – The SOX9 gene is required for Sertoli-cell
considering all aspects, including psychologi- differentiation.
cal care and full disclosure of alternatives relat- – Steroidogenic factor 1 (SF-1) plays a criti-
ing to surgery type and timing. cal role in steroidogenesis, fertility and
• Modern treatment of infants with ambigu- male sexual differentiation.
ous genitalia involves a team-oriented – DAX-1 on the X chromosome is up-
approach. This gender-assignment team regulated in the ovary and functions as an
usually involves neonatologists, geneticists, anti-testis factor.
endocrinologists, surgeons, counselors, and – The Wilms tumor (WT-1) gene is involved
ethicists. The goal is to provide appropriate in both gonadal and renal development.
medical support and counseling regarding Three distinct phenotypes are seen with
care and therapy. WT-1 mutations:
• The Wilms tumor, aniridia, genitouri-
nary anomalies, and mental retardation
31.2 Embryology syndrome, caused by continuous dele-
tion of the WT-1 and PAX-6 genes.
• Normal sexual differentiation is based on the • Denys–Drash syndrome (a triad of pro-
genetic sex (XX or XY), which is established gressive renal disease, 46,XY karyo-
at the time of conception. type with undervirilization, and Wilms
• Until about 7 weeks of gestation, the fetus is tumor. Affected individuals usually
sexually indifferent with two different bipo- have ambiguous genitalia or normal
tential gonads and two internally developing female external genitalia, and streak
wolffian and mullerian ducts. gonads. Nephrotic syndrome presents
• Embryologically, there are two undifferenti- within the first 2 years of life and pro-
ated bipotential gonads in every embryo. gresses rapidly to end-stage renal fail-
• These bipotential gonads develops from the ure within a few years.
urogenital ridge and ultimately develop into • Frasier syndrome (46,XY DSD, gonadal
either a testis or an ovary. dysgenesis, and renal failure), in which
• In addition to these bipotential gonads, fetuses there is an altered ratio of the two splice
of both sexes have two sets of internal ducts: isoforms of the WT-1 protein. Affected
the Müllerian ducts and the Wolffian ducts individuals have normal female external
which develop by 6–7 weeks of intra-uterine genitalia but fail to develop secondary
life. sexual characteristics. Patients are at risk
• At about 7 weeks of gestation: of gonadoblastoma developing in the dys-
– The indifferent gonads and in the presence genetic gonads. Glomerulonephropathy
of a Y chromosome begin to develop into gradually progresses to renal failure in the
testes. second or third decade of life.
“Y” NO “Y”
CHROMOSOME CHROMOSOME
(SRY) (SRY)
NO “SOX9” GENE
“SOX9”GENE INDIFFERENT
INDIFFERENT GONAD
GONAD NO STEROIDOGENIC
STEROIDOGENIC FACTOR 1 (SF-1)
FACTOR 1 (SF-1)
THE WILMS
TUMOR (WT-1)
THE WILMS GENE
TUMOR (WT-1)
TESTIS GENE OVARY DAX-1 ON THE X
CHROMOSOME
• Embryologically, two pairs of ducts are pres- • In females (XX):

ent in each fetus whether a male or female: • The lack of MIS permits Müllerian duct matu-
– The Wolffian ducts ration into Fallopian tubes, uterus, cervix and
– The Müllerian ducts upper vagina.
• In males (XY): – The lack testesterone leads to Wolffian duct
– The indifferent gonads develop into testes. regression.
– The testis has two types of cells: – The Müllerian duct leads to the develop-
• The Sertoli cells ment of:
• The Leydig cells • The uterus
– The testicular Sertoli cells begin secreting • The Fallopian tubes
Müllerian-inhibiting substance (MIS) in • The cervix
the seventh week. • The upper vagina
– The MIS acts only locally (paracrine) to • The testosterone produced by testicular
induce ipsilateral Müllerian duct regression. Leydig cells undergoes peripheral conversion
– The Leydig cells begin producing testos- to dihydrotestosterone, under the effect of the
terone through stimulation via placental enzyme 5α-reductase.
human chorionic gonadotrophin (hCG). • Dihydrotestosterone is important for the
– Testosterone acts both locally (paracrine) development of the external genitalia in
and systemically (endocrine) to stabilize males.
the Wolffian duct, and promotes the devel- • It induces posterior fusion of the genital folds
opment of the epididymis, the vas deferens and growth of the genital tubercle into a phal-
and the seminal vesicle. lic structure.
– The Wolffian duct leads to the development • The development of male external genitalia is
of: complete by 12–16 weeks.
• The epididymis • Subsequent phallic growth is a result of fetal
• The vas deference pituitary luteinizing hormone stimulation of
– The seminal vesicle testicular Leydig cell testosterone production.
31.2 Embryology 641
THE THE
MULLERIAN WOLLFIAN
DUCT DUCT
TESTIS
THE THE
LEIDGE SERTOLI
CELLS CELLS
TESTESTERONE
THE MULLERIAN INHIBITING

SUBSTANCE (MIS)
THE THE VAS THE

EPIDIDYMIS SEMINAL
952DEFERENCE
VESICLE
THE
THE THE UPPER
FALLOPIAN THE CERVIX
UTERUS VAGINA
TUBES
• In females, the non-hormone-dependent sepa- • Gender identity:

ration of the vagina and the urethra is com- – This signifies the child’s self-
plete by 12 weeks. recognition as a boy or a girl, and
• Excess androgen exposure before this sepa- usually starts at 3 years of age.
ration can cause labial fusion and develop- • Gender role:
ment of a phallic urethra or urogenital sinus, – This refers to sex-typical behaviors
but later exposure causes only clitoral such as toy preferences and physical
enlargement and scrotalization of the labial aggression.
folds. • Sexual orientation:
• Psychosexual development: – This refers to the direction(s) of sex-
– Psychosexual development has three main ual interest (heterosexual, bisexual,
components: and homosexual).
– Many factors affect psychosexual develop- • Chromosomal sex determines gonadal sex,
ment, e.g. exposure to androgens, sex chro- which determines phenotypic sex.
mosome genes and brain structure, as well • The type of gonad present determines the dif-
as the society and family perspectives. ferentiation/regression of the internal ducts
– Gender dysphoria indicates unhappiness (Müllerian and Wolffian ducts) and ultimately
with the assigned sex and it results from an determines the phenotypic sex.
inconsistency between the assignment and • Gender identity is determined not only by the
the inherent identity later in life. phenotypic appearance of the individual
– Although gender dissatisfaction occurs but also by the brain’s prenatal and postnatal
more frequently in individuals with DSD development as influenced by the
than in the general population it cannot be environment.
easily predicted from the karyotype, prena- • Early during embryonic development, there
tal androgen exposure, degree of genital are two indifferent or bipotential gonads.
virilization, or assigned gender. • During the second month of fetal life, the indif-
– Several factors influence prenatal androgen ferent (Bipotential) gonad is guided to develop
exposure including the timing, dose and into a testis by genetic information present on
type of androgen exposure, and brain the short arm of the Y chromosome.
receptor availability, as well as the social • This is under the influence of the testis-
environment. determining factor.
– The prenatal period is thought to be critical • The testis-determining factor (TDF) is a 35–
for brain masculinization. kilobase pair (kbp) sequence on the 11.3 sub-
– Girls with congenital adrenal hyperplasia band of the Y chromosome.
(CAH) with marked genital virilization • This is called the sex-determining region of
play more with boys’ toys, and the inci- the Y chromosome (SRY).
dence of homosexuality later in life is • When the SRY is absent or altered, the indif-
higher in this group. ferent gonad develops into an ovary.
– Moreover, sex chromosome genes might • Other genes important to testicular develop-
also influence the brain structure and ment include:
behavior directly. – DAX1 on the X chromosome
– Individuals with complete androgen- – SF1 on band 9q33
insensitivity syndrome (CAIS) however, do – WT1 on band 11p13
not indicate a behavioral role for – SOX9 on bands 17q24-q25
Y-chromosome genes. – AMH on band 19q13.3
• This explain the existence of testicular tissue
in patients with 46, XX testicular DSD, in the
31.3 Sexual and Gonadal absence of an obvious Y chromosome or SRY
Differentiation genetic material.
• The indifferent gonad develops into fetal
• It is important to know that there three types ovaries when the TDF gene (or genes) is
of sex: absent.
– Phenotypic sex • The internal ducts (Müllerian and Wolffian
– Genetic (chromosomal) sex ducts) development results from a paracrine
– Gonadal sex effect from the ipsilateral gonad.
31.3 Sexual and Gonadal Differentiation 643
• In the absence of testicular tissue, the fetus – MIS is a 15-kd protein that is secreted by
internal sex duct and external phenotypic the testis beginning in the eighth fetal
development is that of a female. week.
• The presence of testicular tissue leads to the – It prime role is to repress passive develop-
production of testosterone and Müllerian- ment of the Müllerian ducts:
inhibiting substance (MIS) or AMH which are • Fallopian tubes
important for development of male internal • Uterus
sex ducts and an external male phenotype. • Upper vagina
• Testesterone: – In a normal male fetus with normal testicu-
– Testosterone is produced by testicular lar function, MIS represses Müllerian duct
Leydig cells and induces the primordial development, whereas testosterone stimu-
Wolffian (mesonephric) duct to develop lates Wolffian duct development.
into: • Local testosterone production appears to
• The epididymis enhance the inhibition of Müllerian duct
• The vas deferens development produced by MIS, whereas
• The seminal vesicle estrogens may interfere with MIS action,
– A spatial relation is important in the effect resulting in a degree of Müllerian duct
of testosterone. development.
– Wolffian structures located closest to the • This may explain the variable internal sex duct
source of testosterone undergo the greatest anatomy that occurs in some of the more com-
degree of male differentiation. plex DSDs.
– This explains why patients with ovotes- • The external genitalia:
ticular DSDs often have a degree of – The external genitalia of both sexes are
Wolffian development near testicular tis- identical during the first 7 weeks of
sue, even when joined with an ovary as an gestation.
ovotestis. – Without the hormonal action of the andro-
– No Wolffian development occurs in asso- gens testosterone and dihydrotestosterone
ciation with a streak gonad or a non– (DHT), external genitalia appear pheno-
testosterone-producing dysgenetic testis. typically female.
– High local testosterone levels (paracrine – In the gonadal male, differentiation of the
effect) appear to be necessary for Wolffian external genitalia is moderated by
duct differentiation because maternal testosterone.
ingestion of androgens does not cause – Testosterone is converted to 5-DHT by the
male internal differentiation in a female action of the enzyme, 5-alpha reductase,
fetus, nor does this differentiation occur which is present within the cytoplasm of
in females with CAH (adrenogenital cells of the external genitalia and the uro-
syndrome). genital sinus.
• MIS (Mullerian inhibiting substance): – DHT is bound to cytosol androgen recep-
– MIS is produced by the Sertoli cells of the tors within the cytoplasm and is subse-
testis. quently transported to the nucleus, where it
– It is important to normal male internal duct leads to translation and transcription of
development. genetic material.
The SRY gene (located on the short arm of the Y-

chromosome (Yp11.3))
Testes
Sertoli cells Leydig cells
Testesterone
Anti-Mullerian hormone
Wollfian ducts
956
Mullerian ducts
Epidiymis
Ejaculatory ducts
Dihdrotestesterone Seminal vesicles
Regression
Prostate and external genitalia
Masculinization
– As a result, these actions lead to normal approximately 6 weeks of gestation with a

male external genital development from testosterone rise in response to a surge of
primordial parts: luteinizing hormone (LH).
• The scrotum develops from the genital – Testosterone levels remain elevated until
swellings the 14th week. Most phenotypic differen-
• The shaft of the penis develops from the folds tiation of males occurs during this period.
• The glans penis develops from the tubercle – After the 14th week, fetal testosterone levels
• The prostate develops from the urogeni- settle at a lower level and are maintained more
tal sinus by maternal stimulation through human cho-
– Incomplete masculinization occurs when: rionic gonadotropin (hCG) than by LH.
• Testosterone fails to convert to DHT – Testosterone’s continued action during the lat-
• DHT fails to act within the cytoplasm or ter phases of gestation is responsible for con-
nucleus of the cells of the external geni- tinued growth of the phallus, which is directly
talia and urogenital sinus. responsive to testosterone and to DHT.
– The timing of this testosterone-related – In the gonadal females, differentiation of the
developmental change begins at external genitalia is moderated by estrogen.
– Absence of testosterone leads to regression • In 2006, the Lawson Wilkins Pediatric

of the Wollfian ducts. Endocrine Society (LWPES) and the
– Estrogen secreted by the developing ovary European Society for Pediatric Endocrinology
leads to the development of the external (ESPE) published proposed changes to the
genitalia of the female. previously used nomenclature and definitions
– In the female, the genital tubercle becomes of disorders in which the development of
the clitoris, the labio-scrotal folds become chromosomal, gonadal, or phenotypic sex is
the labia majora, and the urethral folds atypical.
become the labia minora. • The rationale behind these proposals was to
change the nomenclature to reflect advances in
our understanding of the pathophysiology of
31.4 Classification these disorders while being sensitive to the needs
and concerns of patients affected by them.
• In the past, several names were used to
• The previous terminology and the revised
describe disorders of sexual development.
LWPES-ESPE nomenclature are compared
• These include:
below.
– Intersex
• The LWPES-ESPE terminology mainly
– Ambiguous genitalia
reflects the chromosomal sex or the gonadal
– Hermaphroditism
tissue associated with the disorder.
– Sex reversal
Absence of the SRY gene (located on the short arm of

the Y-chromosome(Yp11.3)
Ovary
Estrogen
No Sertoli cells
958
No Anti-Mullerian hormone
External Genitalia
Mullerian ducts
Feminization
The fallopian tubes, Uterus

The upper two-third of the vagina
Previous Terminology and Revised Nomenclature of

Disorders of Sexual Development
PREVIOUS REVISED
• Female • 46,XX DSD

pseudohermaphrodite • 46,XY DSD
• Male pseudohermaphrodite • Ovotesticular DSD
• True hermaphrodite • 46,XX testicular DSD
• XX male • 46,XY complete gonadal
• XY sex reversal dysgenesis
• Currently, all these are grouped under one – The abnormalities include:
common name, disorders of sexual develop- • XX male (46XX)
ment, “DSD”. • 46 XX/45X
• This term is broad and includes common enti- • 46XY/45X Mixed gonadal dysgenesis
ties such as Turner syndrome and Klinefelter • 45,XO Turner (Gonadal dysgensis) and
syndrome as well as rare disorders such as variants
cloacal exstrophy and aphallia. • 47,XXY Klinefelter and variants
• There are several classifications for DSD. • 45X/46XY mixed gonadal disgenesis
• In the past, intersex disorders were subdivided (MGD)
into three main groups: • Chromosomal ovotesticular (True
– Those associated with gonadal dysgenesis hermaphroditism) DSD “46XX/46XY
– Those associated with undervirilization of chimeric type or mosaic type”), (The
46,XY individuals DSD nomenclature has recently
– Those associated with prenatal virilization divided “ovotesticular DSD” (formerly
of 46,XX individuals true hermaphroditism) into 46,XY
• Another commonly used classification divides ovotesticular DSD, 46,XX ovotes-
intersex disorders into four main groups: ticular DSD, and chromosomal ovotes-
– Female pseudohermaphroditism ticular DSD (46,XX/46,XY” chimerism
– Male pseudohermaphroditism or 45,X/46,XY” mosaic type).
– True hermaphroditism – Sex chromosome DSD was formerly termed
– Mixed gonadal dysgenesis as gonadal dysgenesis.
• The new classification of DSD was proposed by – If a testis is poorly formed, it is called a
The Lawson Wilkins Pediatric Endocrine Society dysgenetic testis, and if an ovary is poorly
(LWPES) and the European Society for Paediatric formed, it is called a streak gonad.
Endocrinoloy (ESPE) group as follows: – A patient with a Y chromosome is at high
– Sex chromosome DSDs risk of developing a tumor in a streak or
– 46,XY DSDs dysgenetic gonad.
– 46,XX DSDs – Klinefelter and Turner syndromes are the
• Sex chromosome DSDs: most frequently encountered sex chromo-
– This occurs when the number or structure somal abnormalities.
of the sex chromosomes (X, Y chromo- – The most common genotype of Klinefelter
somes) is abnormal. syndrome is XXY.
with 46,XY chromosomes and incom-

Sex Chromosomes Sexual Disorders pletely masculinized external genitalia.
of Development (DSD) – These patients are characterized by ambigu-
• XX male (46XX) ous or female external genitalia, caused by
• 46 XX/45X incomplete intrauterine masculinization.
• 46XY/45X – Infants with this condition tend to have
• 45,XO Turner (Gonadal dysgensis) and penoscrotal hypospadias, abnormal devel-
variants opment of the testes, and reduced to no
• 47,XXY Klinefelter and variants sperm production.
• 45X/46XY mixed gonadal disgenesis – Some individuals with 46, XY DSD have
(MGD) fully to underdeveloped female reproduc-
• Chromosomal ovotesticular: tive organs (e.g., uterus and fallopian
– 46,XY ovotesticular DSD tubes), while others do not.
– 46,XX ovotesticular DSD – People with 46, XY DSD may be raised as
– Chromosomal ovotesticular DSD males or females.
(46,XX/46,XY” chimerism or – People with 46, XY DSD are at an increased
45,X/46,XY” mosaic type) risk for gonadal tumors and benefit from
regular surveillance or surgery to remove
abnormally developed gonads.
– More than half of girls with Turner syn- – The two main causes of 46,XY DSDs are:
drome have chromosomal mosaicism. • Disorders of testicular development
– The clinical manifestations of patients with • Disorders of androgen synthesis/andro-
45X/46XY MGD, are highly variable, gen action
ranging from partial virilization and ambig- – The spectrum of 46,XY DSDs include:
uous genitalia at birth to a completely nor- • Complete or partial forms of gonadal
mal male or female phenotype. dysgenesis with or without syndromic
– The most common feature of MGD is phenotype
asymmetric development of the testes, • Ovotesticular DSD
often with a dysgenetic testis on one side • Testicular regression syndrome
and a streak gonad on the other. • Androgen synthesis defects
– Asymmetrical external and internal genita- • Disorders of androgen action
lia may also be present. – 46,XY partial gonadal dysgenesis is char-
– Chromosomal ovotesticular DSD (chime- acterized by partial testicular differentia-
ric type or mosaic type) is associated with tion and ambiguous genitalia.
ovarian and testicular tissues found in – 46,XY complete gonadal dysgenesis
either the same or opposite gonad just as in (Swyer syndrome) is characterized by:
46,XX and 46,XY ovotesticular DSD. The • A female phenotype with full develop-
genital duct develops according to the ipsi- ment of unambiguous female genitalia
lateral gonad. • Normally developed Müllerian
• 46,XY disorders of sex development (46,XY structures
DSD): • Streak gonads
– Here, the chromosomes are male but the • These streak gonads should be removed
external genitals are either ambiguous or due to their association with
those of a female. gonadoblastoma.
– The testes may be absent, malformed or • These patients usually present because
normal. of delayed puberty.
– In the past, the term “male pseudoher- – Patients with agonadism (vanishing testic-
maphrodite” was used to describe patients ular syndrome, testicular regression
syndrome) are boys with normal male • Disorders of ovarian development.

genitalia. • Excess exposure to fetal androgen.
– This indicates that these patients must have – SRY positivity; WNT4, RSPO1, b-catenin
had testicular function in the fetal period gene defects; and duplication of SOX9
followed by bilateral anorchia. gene lead to testis-like formation within the
– Androgen synthesis defect can be second- ovary (streak gonad, dysgenetic testis or
ary to: ovotestis) in the 46,XX patients.
• Leydig cell aplasia/hypoplasia, due to
abnormalities in hCG/LH receptor
• Testesterone biosynthesis defects: 46,XY Disorders of Sexual Development
– STAR deficiency (DSD)
– P450scc deficiency • 46,XY disorders of sexual development
– 3-b hydroxysteroid dehydrogenase can be caused by:
type II deficiency – Defects in testicular development
– 17a-hydroxylase and 17,20-lyase – Defects in testosterone biosynthesis
deficiency – Defects in testosterone action
– Isolated 17,20-lyase deficiency – Defects in anti-Mullerian hormone
– P450 oxidoreductase “POR gene” • Defects in testicular development:
defect – 46,XY complete gonadal dysgenesis
– 17b-hydroxysteroid dehydrogenase (Swyer syndrome)
III deficiency – 46,XY partial gonadal dysgenesis
– Disorders of Anti-Mullerian Hormone (Denys-Drash syndrome, Frasier
(AMH) and Anti-Mullerian Hormone syndrome)
receptors result in persistent Müllerian – Ovotesticular DSD
duct syndrome (PMDS). – Testicular regression syndrome (van-
• PMDS is inherited as a sex-limited ishing testes syndrome)
autosomal recessive type. – Leydig cell aplasia/hypoplasia
• It is caused by a mutation in the AMH or • Defects in testosterone biosynthesis:
AMH-receptor genes. – STAR deficiency
• These patients are males and usually – P450scc
present with undescended testis or a – 3-b hydroxysteroid dehydrogenase
hernia. deficiency
• They also have a uterus, Fallopian tube – 17a-hydoxlase and 17,20-lyase deficiency
and rudimentary vagina. – Isolated 17,20-lyase deficiency
– Disorders of androgen action: – P450 oxidoreductase “POR” gene defect
• 5a-reductase type 2 deficiency – 17b-hydroxysteroid dehydrogenase
• Complete/partial forms of androgen III deficiency
insensitivity syndromes – POR gene abnormality (defective
• 46,XX disorders of sex development (46,XX 17,20-lyase activity of P450c17)
DSD): • Defects in anti-Mullerian hormone:
– In this condition, the chromosomes – Persistent Mullerian duct syndrome
(46,XX) and ovaries are of a female but the • Defects in testosterone action:
external genitals appear to be male (mascu- – 5a-reductase type 2 deficiency
linized external genitalia). – Complete androgen insensitivity
– In the past, this was called female syndromes
pseudohermaphroditism. – Partial androgen insensitivity syndromes
– 46,XX DSDs can result either from:
– In ovotesticular DSDs, the most common by the placenta, and is converted to tes-
karyotype is 46,XX followed by tosterone peripherally.
46,XX/46,XY chimerism or mosaicism, • This results in virilization of both fetus
and 46,XY. and mother.
– Most 46,XX ovotesticular DSDs are SRY- • These patients can present during child-
negative, and the genes responsible have hood and adolescence with cystic ova-
not yet been identified. ries and delayed bone maturation. They
– The main cause of a virilized females with may also present at puberty with:
two ovaries, XX karyotype and ambiguous – Primary amenorrhea
genitalia is excess exposure to testosterone – Failure of breast development
before birth. – Virilization
• The excess testosterone exposure is usu- – Hypergonadotrophic hypogonadism
ally of fetal origin
• Rarely this excess is of maternal origin. • Another way of classifying disorders of sexual
– The majority of virilized 46,XX infants development is as follows:
will have congenital adrenal hyperplasia – Disorders of sex chromosomes
(CAH) secondary to enzyme deficiency: – Disorders of gonads
• 21a-hydroxylase deficiency (most – Disorders of phenotype
common)
• 11b- hydroxylase deficiency
• 3b-hydroxysteroid dehydrogenase defi- 46,XX Disorders of Sexual Development
ciency (rare) (DSD)
– A combined P450c17 and P450c21 defi- • 46,XX disorders of sex development:
ciency is a very rare variant of CAH. – Disorders of ovarian development
– Cytochrome POR is a protein that transfers – Excess exposure to fetal androgen
electrons from NADPH to all microsomal • Disorders of ovarian development.
cytochrome P450 enzymes and three ste- – Ovotesticular DSD
roidogenic enzymes, namely: – Gonadal dysgenesis
• P450c17 (17a-hydroxylase/17,20 lyase) – Vaginal atresia
• P450c21 (21-hydroxylase) – Cloacal exstrophy
• P450aro (aromatase) • Excess exposure to fetal androgen
– Mutations of POR gene cause disordered – Congenital adrenal hyperplasia
steroidogenesis with prenatal virilization. • 21a-hydroxylase deficiency (most
– Causes of fetal androgen excess in XX common)
infants are rare and include: • 11b- hydroxylase deficiency
• Maternal androgen ingestion • 3b-hydroxysteroid dehydrogenase
• Maternal virilizing disease deficiency (rare).
• Fetoplacental aromatase deficiency – P450c17 (17a-hydroxylase/17,20
• Virilizing luteoma of pregnancy lyase) deficiency
• Glucocorticoid receptor mutation – P450c21 (21-hydroxylase) deficiency
– Aromatase enzyme deficiency: – P450aro (aromatase) deficiency
• This is rare type of enzyme deficiency. – Maternal excess of androgens:
• Aromatase is the enzyme that catalyzes • Maternal androgen ingestion dur-
conversion of androgens into estrogens. ing pregnancy
• As a result of this enzyme deficiency, • Fetoplacental aromatase deficiency
DHEA produced by the fetal adrenal • Virilizing luteoma of pregnancy
glands cannot be converted to estrogen
A comprehensive classification (Aaronson’s ATROPHIC

classification) based on gonadal histology TESTIS
1. Ovarian DSD:
• The gonads are composed of normal
ovarian stroma with numerous VAS
follicles. DEFERENCE
2. Ovotesticular DSD:
• The gonads are essentially composed
of both ovarian and testicular tissues,
either in two separate gonads or
within a single gonad. Fig. 31.10 A clinical intraoperative photograph showing
• At the least, a well-defined ovarian atrophic testis. Note the presence of a vas
follicle should be seen to diagnose
the ovarian element. • Mixed gonadal dysgenesis 46XY/45X
• The testicular component comprises • True hermaphroditism 46 XX, 46XY or
architecturally ordered tubules, mosaics
although the intervening stroma may • Disorders of gonads (Gonadal sex) (Figs. 31.10
be more abundant than normal. and 31.11):
3. Testicular DSD: – Disorders of gonadal sex result when chro-
• The seminiferous tubules are normal, mosomal sex is normal but differentiation
although Leydig cells might be of the gonads is abnormal.
prominent. – The abnormalities include:
4. Dysgenetic DSD: • Pure gonadal dysgenesis
• The tubules are disordered, often • Dysgenetic testes
sparse, and the stromal tissue is • Absent testes
abundant. • Disorders of phenotype (Phenotypic sex):
• These gonads have a strong propensity – In these disorders the gonads and sex chro-
to undergo malignant degeneration. mosomes are normal but with abnormal
urogenital tract.
– The abnormalities include:
• Female pseudohermaphrodite
• Disorders of sex chromosomes (Chromosomal • Congenital adrenal hyperplasia
sex): • Nonadrenal female
– This occurs when the number or structure pseudohermaphroditism
of the sex chromosomes (X, Y chromo- • Developmental disorders of mullerian
somes) is abnormal. duct
– The abnormalities include: • Male pseudohermaphrodite
• Klinefelter syndrome 47 XXY • Abnormalities in androgen synthesis
• XX male (46XX) • Abnormalities in androgen action
• Turner syndrome (gonadal dysgenesis) • Persistent mullerian duct synd
45 XO • Developmental defects of male
• 46 XX/45X genitalia
31.5 Evaluation of a Newborn with DSD 651
Fig. 31.11 Intraopera-

tive photograph showing
bilateral atrophic testes ATROPHIC ATROPHIC
TESTIS TESTIS
31.5 Evaluation of a Newborn • 45,X0 or 45,X0/46,XY (Turner’s

with DSD syndrome)
• Seminiferous tubule dysgenesis:
• The evaluation, diagnostic approach and man-
Klinefelter’s syndrome (47,XXY)
agement of a newborn with DSD involves a
2. 46,XX (DSD)
multidisciplinary team approach.
• Androgen excess: (60–70 %)
• This team include:
– CAH (vast majority)
– Neonatologists
• 21-Hydroxylase deficiency (95 %)
– Geneticists/genetic counselor
• 11β-Hydroxylase deficiency (5%)
– Pediatric endocrinologists
• 3β-Hydroxysteroid dehydroge-
– Pediatric surgeons
nase deficiency
– Social worker
– Maternal androgens (very rare)
– Pediatric urologist
• Endogenous: Virilising
– Psychologist
tumours in the mother
• The most common disorder of sexual develop-
• Exogenous (very rare)
ment (DSD), congenital adrenal hyperplasia
• Disorders of ovarian development
(CAH), results in virilization of a 46,XX
– Ovotesticular DSD
female.
– 46,XX testicular DSD (SRY
• The clinician’s challenge is to distinguish
translocation)
CAH from other less common causes of
– Pure gonadal dysgenesis (e.g.
ambiguous genitalia.
SOX9 duplication
• Meyer–Rokitansky syndrome (Müllerian
aplasia)
Classification of DSD 3. 46,XY DSD
1. Sex chromosome DSD • Disorders of testicular development
• 45,X0/46,XY Mixed gonadal dys- – Gonadal dysgenesis (Swyer syn-
genesis (MGD) drome = Pure, DAX-1 Duplication.
• 45,X0/46,XY Partial gonadal SF-1 mutation)
dysgenesis – Ovotesticular DSD
• 46,XX/XY or 45,X0/46,XY – Bilateral vanishing testis/testicu-
Ovotesticular DSD lar regression syndromes
– During the evaluation stage, the newborn is

• Disorders of androgen synthesis or referred to as “baby,” not boy or girl.
action – The family should be encouraged to delay
– Leydig cell agenesis, unresponsiveness naming the baby until the sex has been
– Enzyme deficiency assigned.
• StAR deficiency (lipoid adre- • There are other factors that must be taken in
nal hyperplasia consideration during this process including:
• 3β-Hydroxysteroid dehydroge- – The social and cultural background.
nase deficiency – Expectations of the parents.
• 17α-Hydroxylase deficiency – Religious factors.
• 17,20-Lyase deficiency • The parents are also involved, educated and
• 17β-Hydroxysteroid oxidore- should participate in the process and should
ductase deficiency understand that a children with a DSD can live
• 5α-Reductase deficiency normal live and function well in society.
• Disorders of androgen-dependent • Although different DSDs may present with
target tissue similar findings on physical examination,
– CAIS (testicular feminisation) there are certain clinical and laboratory
– PAIS aspects that are important and will help define
• Persistent Müllerian duct syndrome the type of DSD.
4. Others: Severe hypospadias and crypt- • It is important to rule out a malformation syn-
orchidism, penile agenesis and cloacal dromes that may present as ambiguous genita-
exstrophy lia (Fig. 31.12).
• Clinical evaluation of the gonads and external
genitalia is very important:
• A detailed family history is essential; the fol- – It is important to note the size and degree
lowing considerations should be kept in mind: of differentiation of the phallus.
– A family history of genital ambiguity, – Note the phallus length:
infertility, or unexpected changes at • A normal-term male penis is 3.5 ± 0.7 cm.
puberty may suggest a genetically trans- • A length of less than 2.0 cm is consid-
mitted trait. ered abnormal.
– Recessive traits tend to occur in siblings, • A normal-term female clitoris is less
whereas X-linked abnormalities tend to than 1.0 cm.
appear in males who are scattered sporadi- • Micropenis is thus defined as a stretch
cally across the family history. penile length of less than 2.0 cm in a
– A history of early death of infants in a fam- term male infant, and clitoromegaly as a
ily may suggest a previously missed adre- clitoris greater than 1.0 cm in a term
nogenital deficiency female. In preterm infant males, the
– Maternal drug ingestion is important, par- penile length is shorter.
ticularly during the first trimester, when – Note the position of the urethral meatus:
virilization may be produced exogenously • Hypospadias associated with bifid scro-
in a gonadal female. tum or undescended testis suggests a
– Although extremely rare, a history of DSD (Figs. 31.13 and 31.14).
maternal virilization may suggest an • If the urethral opening is at the base of
androgen-producing maternal tumor the phallus, it could be a urogenital
(arrhenoblastoma) sinus in a virilized female.
• Sex assignment: – Labioscrotal folds may be separated or be
– It is important not to assign a sex immedi- fused at the midline, giving an appearance
ately and delay it till after full evaluation. of a scrotum.
– Newborns with 46XX DSD due to CAH • Impalpable gonads, even in an appar-
may have hyperpigmented labioscrotal folds. ently fully virilized infant, should raise
– The anogenital ratio: the possibility of a severely virilized
• This is the distance between the anus 46XX DSD patient with CAH.
and posterior fourchette divided by the • The presence of two palpable gonads
distance between the anus and base of strongly favors the diagnosis of a 46XY
the clitoris/phallus. DSD.
• A ratio greater than 0.5 suggests • The presence of only one palpable
virilization. gonad suggests the diagnosis of mixed
• In a fully virilized male the ratio is 1.0. gonadal dysgenesis, although it does not
– Documentation of palpable gonads is also rule out a 46 XX ovotesticular DSD.
important:
• Although ovotestes have been reported
to descend completely into the bottom of 31.6 Diagnosis and Investigations
labioscrotal folds, in most patients, only
testicular components descends fully. • The optimal care of patients with DSD
• If clinical evaluation reveals palpable requires a multidisciplinary team and begins
gonads in the inguinal area, the in the newborn period.
diagnoses of pure gonadal dysgenesis • Some cases of DSD are obvious at birth while
can be eliminated. others are diagnosed during childhood or
remain undiagnosed until a child reaches
puberty.
• The investigations depend on the suspected
type of DSD.
• The diagnostic evaluation of DSD includes:
– A complete CBC and electrolytes
– Hormone measurements
– Hormone stimulation tests
– Diagnostic radiological evaluations
• Ultrasonography shows the presence or
absence of Müllerian/Wolfian structures
Fig. 31.12 A clinical photograph of a newborn with and can locate the gonads and their echo
DSD. Note also the associated anorectal agenesis texture.
Figs. 31.13 and

3.14 Clinical
photographs showing
severe degrees of
hypospadias. Note the
bifid scrotum also
• Ultrasonography also can identify asso- diagnosis of 21-hydroxylase

ciated malformations such as renal deficiency.
abnormalities. – MGD, ovotesticular, and 46,XY DSD
– Cytogenetic and molecular studies remain as diagnostic possibilities.
– Endoscopic, laparoscopic and gonadal • If two gonads are palpable:
biopsy – 46,XY DSD and ovotesticular DSD
– Retrograde genitogram is performed for are the most likely diagnoses.
the anatomical outlining of the urogenital – Symmetrical external genitalia, with
sinus and for localizing the position and or without palpable gonads, and an
entry of the urethra and vagina into the absent uterus suggest an underviril-
sinus. ized XY male.
– The genetic evaluation includes: – The presence of a uterus and asym-
• Chromosomal analysis (Karyotype) metric external genitalia and palpable
• FISH gonad(s) suggest gonadal dysgenesis
• Specific molecular studies to screen the with Y and ovotesticular DSD.
presence of mutations or gene dosage – A gonadal biopsy is required to clas-
imbalance (AR, SRY, SF1, WT1, sify the type of gonadal dysgenesis
CYP21, SOX9, DAX-1, 17b hydroxys- and ovotesticular DSD, to assess
teroid dehydrogenase, 5a-reductase-2, gonadal chromosomal mosaicism
and others). These are not readily and to detect the presence of a
avaliable. gonadal tumor.
• Current molecular diagnosis is limited – Hormone measurements should include
by cost, accessibility, and quality hCG and ACTH stimulation tests to assess
control. testicular and adrenal steroid biosynthesis.
– Common findings suggesting DSD are: – The endocrine evaluation of patients with
• A male appearance with associated 46,XY DSDs and sex chromosome DSDs
abnormalities of genitalia including: include assessment of testicular function
– Severe hypospadias with bifid by basal measurement of LH, FSH, inhibin
scrotum B, Testesterone, Dihyrotestesterone (DHT),
– Undescended testis/testes with Anti-Mullerian hormone (AMH), and
hypospadias DHEAS.
– Bilateral non-palpable testes – In patients with Testesterone synthesis
– Micropenis with chordee. defects, neonatal and post pubertal diagno-
• A female appearance with associated sis is made based on basal steroid levels.
abnormalities of genitalia including: – Testesterone stimulation test:
– Enlarged clitoris • The stimulation of Testesterone produc-
– Posterior labial fusion tion by hCG is used to determine abnor-
– An inguinal/labial mass. malities in Testesterone biosynthesis
– The location of the gonads and presence or and also to document the presence of
absence of a uterus, will provide a provi- functioning testicular tissue.
sional clinical diagnosis. • Testosterone and DHT should be mea-
• If no gonads are palpable: sured at baseline and 72 h after hCG
– 46,XX DSD (with two ovaries) is the stimulation.
most commonly seen. • The increase in the level of Testesterone
– MGD. should be at least threefold.
– The presence of a uterus and absence • A failure to respond to hCG in combina-
of palpable gonads in a virilized tion with elevated LH/FSH levels and
female primarily suggest a clinical low/undetectable value of AMH is
consistent with anorchia or gonadal • AMH level will be elevated during the
dysgenesis. first year of life and at puberty in those
• Androgen insensitivity should be con- with androgen insensitivity.
sidered in individuals with a 46,XY • In 46,XX patients with DSDs, a high
karyotype and with normal Testesterone serum AMH level is indicative of the
biosynthesis. presence of testicular tissue.
• Patients with 5a-reductase deficiency – The diagnosis of 21-hydroxylase deficiency
have normal Testesterone levels, low or in 46,XX DSDs with two ovaries depends on:
normal DHT levels and a high • The detection of elevated 17-OHP lev-
Testesterone/DHT ratio after hCG stim- els either as a basal measurement or
ulation test. after a short ACTH stimulation test.
– The testosterone level can help to deter- • High concentration of 11-deoxycortisol
mine whether the DSD is due to a lack of and deoxycortisol (DOC) with low lev-
androgen or cortisone synthesis or rather els of plasma renin activity (PRA).
due to a receptor defect. • This will help differentiate 11- hydroxy-
– An elevated level of 17-hydroxyprogesterone lase from 21-hydroxylase deficiency.
is diagnostic of CAH. – Study of androgen target cells:
– Determining the levels of 11-deoxycortisol • Defects in peripheral sensitivity to
and deoxycorticosterone will help to make androgens may be responsible for geni-
a differential diagnosis between tal ambiguity in male individuals with
21-hydroxylase and 11β-hydroxylase defi- partial androgen insensitivity.
ciencies. If the levels are elevated, a diag- • Androgen receptor activity can be deter-
nosis of 11β-hydroxylase deficiency could mined in fibroblasts grown from a geni-
be made, whereas low levels confirm tal skin biopsy sample.
21-hydroxylase deficiency. • 5-alpha reductase activity can be deter-
– The diagnosis of 17bHydroxysteroid dehy- mined by this method.
drogenase deficiency is made when a 10- to – Chromosomal characteristics, gonadal his-
15-fold elevation is observed in the ratio of tology and presence or absence uterus are
A/T. taken into consideration in the classifica-
– Inhibin B and AMH are useful markers for tion of DSDs.
the presence of Sertoli cells and their – In rare cases in which a definite diagnosis
assessment could help in the diagnosis of cannot be determined and in infants with
testis determination disorders. intra-abdominal or nonpalpable testes in
– Serum AMH level: whom DSDs are considered, open or lapa-
• This is indicative of the presence of tes- roscopic exploration with biopsy of the
ticular tissue. gonads could become necessary.
• In boys with bilateral cryptorchidism, – In some cases, the differential diagnosis of
serum AMH correlate with the presence DSD depends on the interpretation of the
of testicular tissue. histologic features of the gonads.
• Undetectable values are highly sugges- – Infants with intra-abdominal or nonpalpa-
tive of absence of testicular tissue. ble testes in whom the precise diagnosis is
• In XY patients, AMH is low in those unavailable with karyotyping and serum
with DSD secondary to abnormal study will require an open or laparoscopic
testicular determination (including com- exploration with bilateral deep longitudinal
plete and partial gonadal dysgenesis). gonadal biopsies for histologic evaluation,
• AMH will be normal or elevated in which will determine the presence of ovo-
patients with impaired Testesterone testes, streak gonads, or dysgenetic testes,
secretion. thereby confirming the diagnosis.
31.7 Management of Patients • Some of these patients have deficiencies

with DSD of glucocorticoids and/or mineralocorti-
coids and these are treated with gluco-
• The management of patients with DSD corticoids and/or mineralocorticoids.
depends on the underlying cause. • Patients with hypospadias require
• Supplemental hormone therapy may be given urethroplasty.
if gonadal function is compromised. • Testosterone replacement may be
• In a virilized female, the surgical management required at puberty, particularly if tes-
is feminizing genitoplasty and this includes tosterone levels remain low.
vaginoplasty and clitoroplasty. – 5-alpha-reductase deficiency
• Undervirilized males typically have hypospa- • These patients are assigned a male sex.
dias and this is corrected with urethroplasty. • Fertility is preserved.
• Gender reassignment may be considered in • Patients with hypospadias require
patients with 46XY males and inadequate urethroplasty.
external genitalia. • These patients do not typically require
• Sex assignment and therapy: hormonal replacement and the rise in
– There are several factors which must be con- testosterone levels at the onset of
sidered during sex assignment, including: puberty is sufficient to induce develop-
1. The phenotype ment of secondary sexual
2. The appearance of the genitals characteristics.
3. The surgical options – Partial androgen resistance
4. The need for future hormonal replace- • Most of these patients are raised as
ment therapy males and fertility is preserved.
5. The potential for future fertility • Some patients with severe partial andro-
6. The culture and preferences of the gen resistance may be raised as females,
family as adequate virilization at puberty may
7. The effect of high levels of testosterone not be possible.
exposure on the brain development • If the patient is raised as a male, early
• Sex assignment also depends on the type of surgical correction of hypospadias is
DSD (46XX DSD, 46XY DSD or chromo- recommended.
somal DSD) • Testosterone replacement may be
• 46 xx chromosomes: required at puberty, particularly if tes-
– Congenital adrenal hyperplasia: tosterone levels remain low.
• These patients are usually assigned a • If the patient is raised as a female:
female sex. – Early vaginoplasty is recommended.
• Their fertility is preserved. – Clitoroplasty in those with severe
• These patients are given hydrocortisone virilization.
to replace cortisol, and, if there is – These patients require gonadectomy
associated salt wasting, fludrocortisone before puberty to prevent virilization
is given to replace aldosterone. at puberty and also malignant
• Surgical treatment is required to correct transformation.
the external genitalia. This should be – Estrogen supplements are required at
done early and includes: puberty to allow development of sec-
– Clitoroplasty. ondary sexual development.
– Vaginoplasty – Gonadal dysgenesis
• 46 XY chromosomes: • The sex assignment in these patients
– Testosterone biosynthesis defects depends on several factors including:
• These patients are assigned a male sex. – The likelihood of fertility.
• Fertility is preserved. – The genital appearance.
31.8 Surgical Corrections of DSD 657
– The size of the phallus. – Gonadectomy should be performed

– The presumed testicular function in early to prevent malignancy and
puberty which is based on hormonal avoid any risk of virilization.
tests and gonadal development. – Estrogen supplements at puberty to
• If the patient is raised as a female: allow development of secondary sex-
– Early vaginoplasy is recommended. ual development.
– Clitoroplasty in those with severe – Some of these patients have
virilization. Mullerian structures (uterus) and
– Gonadectomy before puberty to pre- need treatment with cyclic progester-
vent virilization at puberty and pos- one once breakthrough bleeding
sible malignant transformation. occurs.
– Estrogen supplements at puberty to
allow development of secondary sex-
ual development. 31.8 Surgical Corrections of DSD
• If the patient is raised as a male:
– Early surgical correction of hypospa- • The aims of corrective surgery for patients
dias is recommended. with DSD are:
– Testosterone replacement may be – To make ambiguous external genitalia
required at puberty, particularly if compatible with assigned gender
testosterone levels remain low. – To prevent urinary obstruction or infections
– 45 X/ 46 XY mixed gonadal digenesis – To preserve sexual and reproductive
• Sex assignment is more complex in potentials
these patients. – To maximize anatomy to enhance sexual
• If fertility is likely to be maintained, function
then sex assignment is best chosen to be • Surgical corrections are aimed at:
consistent with fertility. – The gonads
• Other factors that must be taken in con- – The external
sideration including: – The presence of a urogenital sinus
– The genital appearance • In general, it is recommended that the deci-
– The size of the phallus. sion about reconstructive genital surgery
– The presumed testicular function in should be made by the parents and, when pos-
puberty based on hormonal tests and sible, the patient. This should be taken under
gonadal development. the counseling and advice of the treating med-
• The risk of gonadal malignancy is high- ical team.
est in mixed gonadal dysgenesis in • It is important to inform the parents that a
which there is a Y chromosomal and in functional outcome is more important than a
those with an intra-abdominal testis. cosmetic outcome.
• In children assigned a male sex, hypo- • It is also important to inform the patients and
spadias is corrected with urethroplasty. parents not to have unrealistic expectations
• A streak ovary, if present, should be about penile reconstruction.
removed. • Genital reconstructive surgery in infancy that
• Testosterone replacement may be makes an appearance consistent with the gen-
required at puberty, particularly if tes- der of rearing is of significant psychological
tosterone levels remain low. support to the family.
• In children assigned a female sex, the fol- • Others feel that corrective surgery is not
lowing corrective procedures are required: urgent and that it is more appropriate to delay
– Early vaginoplasty. surgery until a patient is old enough to be
– Clitoroplasty in those with severe informed fully and to participate in decision
virilization. making.
• In a virilized female, the surgical procedure is dilatations are more feasible to prevent
termed feminizing genitoplasty and includes vaginal stenosis. To prevent stenosis, vagi-
vaginoplasty and clitoroplasty. The optimal nal dilatation can begin 2 weeks after the
timing of feminizing genitoplasty is still operation.
controversial. – Labioplasty is performed at the time of the
• The American Academy of Pediatrics guide- vaginoplasty and gives the external genita-
lines on the timing of genital surgery lia a normal female appearance.
recommend feminizing genitoplasty between – During clitoroplasty, the remnant skin from
2 and 6 months of age and many pediatric the clitoris shaft could be used to make the
urologists also recommend early feminizing labia minora and majora.
genitoplasty. • Phaloplasty:
• Feminizing genitoplasty for the infants who – Currently, there is no tissue available to
are to be raised as females includes: increase the size of an underdeveloped
– Removing the corporal bodies phallus.
– Creating a normal-looking introitus and – In patients with DSD associated with hypo-
labia minora and majora spadias, the complexity of this procedure
– Vaginoplasty to provide an adequate vagi- must be discussed with the parents during
nal opening the initial counseling.
• Masculine reconstruction may include: – The standard surgical repair include:
– Orchidopexy • Increase penile size and length with top-
– Repair of hypospadias ical or injectable testosterone.
– Excision of retained Müllerian duct struc- • Chordee correction
tures when present • Repair of hypospadias
• Clitroplasty: • Gonadectomy:
– Clitoroplasty should be considered only in – There is controversy regarding the timing
cases of severe virilization. of gonadectomy.
– It should be performed combined with – It is recommended that gonadectomy
repair of the common urogenital sinus. should be performed soon after diagnosis
– Until the 1960s, the principal surgical proce- because estrogen-replacement therapy
dure for clitoromegaly was clitoridectomy. could be started.
– Clitoridectomy results in a near normal look- – Others prefer delayed gonadectomy.
ing female perineum but it will affect the – The advantages of late gonadectomy
orgasmic function and erectile sensation. include breast development and avoidance
– Clitoridectomy is currently contraindicated. of poor adolescent compliance with
– The preferred procedure is clitoral reduc- estrogen-replacement therapy.
tion. This spares the neurovascular bundle – Germ cell malignancy only occurs in
which is important for the preservations of patients with DSD who have
intact orgasmic function and erectile Y-chromosomal material (GBY region).
sensation. – Testes in patients with 46,XY gonadal dys-
• Vaginoplasty: genesis who are raised as a female should
– Some authors prefer to correct the external be removed to prevent testicular
genitalia in a single-stage procedure in the malignancy.
newborn period to take advantage of all – In patients with androgen biosynthetic
native genital tissue and to avoid subse- defects raised who are raised as females,
quent scarring. gonadectomy should be performed before
– This is also advantageous to the parents. puberty.
– Others advocate delaying vaginal recon- – A scrotal testis in patients with gonadal
struction until puberty when vaginal dysgenesis is at risk for malignancy. The
31.9 Congenital Adrenal Hyperplasia (CAH) 659
current recommendations are to perform 31.9 Congenital Adrenal

testicular biopsy at puberty to diagnose Hyperplasia (CAH)
carcinoma in situ or undifferentiated intra-
tubular germ cell neoplasia, which are pre- • CAH is the most common cause of DSD in the
malignant lesions. If positive, the option is newborn.
sperm banking before treatment with local • In the past, patients with CAH were called
low-dose radiotherapy. female pseudohermaphrodites.
– In female patients with ovotesticular DSD, • CAH accounts for 60–70 % of ambiguous
the tumor risk is low (<5 %), but removal of genitalia in a newborn.
the testicular component in early life is rec- • It is characterized by the followings:
ommended to preserve fertility potential. – The gonads are ovaries bilaterally.
• Medical and psychotherapy: – The Müllerian system develops normally
– Hypogonadism is common in patients into Fallopian tubes, uterus and upper
with: vagina.
• Dysgenetic gonads – The Wolffian system derivatives regresses.
• Defects in sex-steroid biosynthesis – The karyotype is 46,XX.
• Resistance to androgens • The basic biochemical defect is an enzymatic
– Hormone-replacement therapy is often block that prevents sufficient cortisol produc-
required in patients with DSD to: tion. Biofeedback via the pituitary gland
• Induce and sustain puberty causes the precursor to accumulate above the
• Induce secondary sexual characteristics block. Clinical manifestation of CAH depends
• Induce pubertal growth spurt on which enzymatic defect is present.
• Optimize bone mineral accumulation • The metabolic and biochemical consequences
• Help with psychosocial maturation of CAH are variable.
– Boys with hypogonadism require intramus- • The majority of CAH cases (95 %) are due to
cular injections of either testosterone cypio- an autosomal recessive deficiency of
nate or ethanate for pubertal induction. 21-hydroxylase.
– Other testosterone preparations such as • As a result of this enzyme deficiency, the adre-
gels and patches are also available. nal gland is unable to form cortisone and the
– In girls with hypogonadism, estrogen sup- adrenal steroid hormone synthesis is diverted
plementation to induce secondary sexual towards the androgen pathway, resulting in
changes and menstruations is required. virilization.
• Estrogen can be given orally, by injec- • In 75 % of the cases, the deficiency affects
tion, or patch. both cortisone and aldosterone production.
• A progestin is usually added after break- This also results in salt loosing.
through bleeding develops or within • If the zona glumerulosa is spared, aldoste-
1–2 years of continuous estrogen. rone production remains normal and only
– Psychosocial care should be an integral simple virilization without salt wasting
part of the management of patients with (25 %) results.
DSD to promote positive adaptation. • The second most common enzyme deficiency
• Families and individuals require ongoing is 11β-hydroxylase.
counseling by experienced personnel. – The characteristic feature of this enzyme
• Other important resources include deficiency is the accumulation of desoxy-
access to confidential sexual counseling corticosterone that causes salt retention
and support groups. and hypertension.
• Regular follow-up from infancy to • Virilization of the external genitalia varies
adulthood of sexual, psychological, and from minimal phallic enlargement to almost
social parameters is important. complete masculinization.
• Because of the andrenocorticotropic hormone • Biochemically, 75 % of patients have salt-

drive there is hyperpigmentation of the exter- wasting nephropathy. Before this condition
nal genitalia and nipples. was commonly recognized, as many as one
• These patients are raised as females especially third of patients presented with evidence of
those with mild to moderate virilization. vascular collapse.
• Fertility is normally expected in these patients. • The 21-hydroxylase defect is inherited as an
• A prenatal diagnosis of CAH in high-risk fam- autosomal recessive trait closely linked to the
ilies is possible via: human leukocyte antigen (HLA) locus on
– Determination of an elevated chromosome 6. The transmitted trait may have
17-hydroxyprogesterone in amniotic fluid two varieties, which helps account for the
– Human leukocyte antigen genotyping of clinical heterogenicity seen in patients with
chorionic villus samples salt-wasting nephropathy.
• However, the diagnosis cannot be confirmed • Diagnosis is confirmed by an elevated serum
before the initial development of the external level of 17-OHP.
genitalia. – Reference range newborn cord blood levels
• Medical treatment with life-long cortisone of 17-OHP can be as high as 900–5,000 ng/
replacement after birth is mandatory. dL, but the serum level rapidly decreases
• Mineralocorticoteroids are indicated in those by the second or third day of life.
with salt wasting CAH. – A repeat elevated serum value exceeding
• The incidence of CAH to be 1 case per 15,000 500 ng/dL at this point makes the diagnosis
live births. highly likely.
• Frequency was highest in neonates of – It should be kept in mind that 17-OHP lev-
European Jewish, Hispanic, Slavic, or Italian els may be markedly elevated in the
descent. 11-hydroxylase form of CAH, as well as in
• Male infants with this syndrome may be phe- the rare child with the 3-beta-hydroxysteroid
notypically normal, and the diagnosis may be dehydrogenase form.
missed. • CAH presents a spectrum of abnormalities,
• CAH may result from several metabolic defects, including (Figs. 31.15, 31.16, 31.17, and
one of which is 21-hydroxylase deficiency. 31.18):
• In 90 % of patients with CAH, the block is at – The degree of phallic enlargement
the 21-hydroxylation enzyme. This leads to a – The extent of urethral folds fusion
mineralocorticoid deficiency and a buildup of – The size and level of entry of the vagina
androgenic byproducts, which causes mascu- into the urogenital sinus
linization of a female fetus. • The level of entry of the vaginal opening into
• The result is a female infant with varying the urogenital sinus is divided into two types
degrees of virilization. (Figs. 31.19, 31.20, 31.21, and 31.22):
Figs. 31.15 and 3.16 Clinical photographs showing congenital adrenal hyperplasia. Note the degree of phallic
enlargement and the extent of urethral folds fusion
Figs. 31.17 and 3.18 Clinical photographs of a patient with CAH showing virilization of external genitalia
URINARY BLADDER
VAGINA
URINARY BLADDER
VAGINA
Figs. 31.19 and

3.20 Genitograms
showing the level of
entry of the vaginal
opening into the UROGENITAL SINUS
urogenital sinus. This
shows a low level of
insertion
Fig. 31.21 Diagram-

urogenital sinus
showing high insertion
of the vaginal opening UTERUS
into the urogenital
sinus. Note the point URINARY
of entry above the BLADDER
VAGINA
sphincter
SPHINCTER
RECTUM
Fig. 31.22 Diagram-

urogenital sinus showing
low insertion of the
vaginal opening into the
urogenital sinus. Note UTERUS
the point of entry below
URINARY
the sphincter BLADDER
VAGINA
SPHINCTER
RECTUM
– Below the urethral sphincter – Rarely, CAH is caused by maternal

– Above the urethral sphincter androgens
• The internal Müllerian structures are well – 21-Hydroxylase deficiency:
developed in these patients and females with • This is the commonest cause seen in
this condition are usually fertile with the 90 % of patients with CAH.
ability to become pregnant and give birth. • This leads to a mineralocorticosteroid
• There is a salt-losing variety of CAH and this deficiency.
is fatal in infants if left untreated as it causes • As a result of this, there is accumulation
hypotension which can cause vascular col- of androgenic byproducts, which causes
lapse and death. masculinization of a female external
• Causes of CAH: genitalia.
– CAH is commonly caused by enzyme defi- • The end result is a female infant with
ciencies in the sex hormones pathway as varying degrees of virilization.
follows: • A large number of these patients (75 %
• 21-Hydroxylase deficiency of patients) have also salt-wasting. This
• 11-Hydroxylase deficiency is a serious condition which must be
• 3-Beta-hydroxysteroid dehydrogenase recognized and treated to avoid vascular
deficiency collapse.
• The 21-hydroxylase deficiency is heredi- – The 17-Hydroxyprogesterone level

tary inherited as an autosomal recessive trait. is mildly elevated.
• The transmitted trait may have two vari- – There is accumulation of deoxycorti-
eties, which explains the clinical hetero- costerone and 11-deoxycortisol.
genecity seen in patients with – 3-Beta-hydroxysteroid dehydrogenase
salt-wasting nephropathy. deficiency:
• CAH can be diagnosed prenatally by • A less frequently seen version of CAH
demonstrating an elevated amniotic is caused by 3-beta-hydroxysteroid
fluid level of 17-hydroxyprogesterone dehydrogenase deficiency.
(17-OHP) during the second trimester • This version causes less severe viriliza-
or by HLA typing of amniotic cells. tion of a female infant than the viriliza-
• CAH is commonly diagnosed in new- tion caused by 21-hydroxylase or
borns during evaluation of a 46XX new- 11-hydroxylase deficiency.
born with ambiguous genitalia and the • The buildup of pregneninolone, which
diagnosis is confirmed by demonstrat- is subject to hepatic conversion into tes-
ing an elevated serum level of tosterone, produces the virilization.
17-hydroxyprogesterone. • These patients can present with a salt-
• 17-Hydroxyprogesterone levels may be losing crisis caused by deficient miner-
elevated also in the 11-hydroxylase defi- alocorticoid production, similar to that
ciency form of CAH, as well as in the occurring with 21-hydroxylase
rare type seen in those with the 3-beta- deficiency.
hydroxysteroid dehydrogenase • The diagnosis can be confirmed by
deficiency. identifying an elevated serum level of
– 11-Hydroxylase deficiency: dehydroepiandrosterone or its sulfate
• Another cause of CAH is 11-hydroxylase metabolite.
deficiency. • It should be kept in mind that 3-beta-
• Patients who have CAH with hydroxysteroid dehydrogenase defi-
11-hydroxylase block accumulate ciency is the only common form of
deoxycorticosterone (DOC) and CAH that can also cause ambiguity in
11-deoxycortisol. the genetic male. This ambiguity occurs
• This form of the syndrome exhibits salt because the enzyme defect is present in
retention and hypertension because both the adrenal glands and the testes,
DOC is a potent mineralocorticoid. leading to inadequate production of tes-
• The diagnosis can be confirmed by a tosterone in utero.
steroid screen of the serum. • 3-beta-hydroxysteroid dehydrogenase
• CAH secondary to 11-hydroxylase deficiency is the only common form of
deficiency leads to accumulation CAH that can also cause ambiguous
deoxycorticosterone (DOC) and genitalia in the genetic male.
11-deoxycortisol. • This ambiguous genitalia occurs
• CAH secondary to 11-hydroxylase defi- because this enzyme defect is present in
ciency should be suspected in a 46XX both the adrenal glands and the testes,
child with ambiguous genitalia in leading to inadequate production of tes-
whom: tosterone in utero.
Cholesterol
20, 22 Desmolase
17β-Hydroxysteroid
17α-Hydroxylase 17-20 Desmolase Oxidoreductase
Pregnenolone 17-OH Pregnenolone Dehydroepiandrosterone Androstenediol
3 β-Hydroxysteroid 3 β-Hydroxysteroid 3 β-Hydroxysteroid 3 β-Hydroxysteroid

Dehydrogenase Dehydrogenase Dehydrogenase Dehydrogenase
17β-Hydroxysteroid
17α-Hydroxylase
Progestrone 17-20 Desmolase Oxidoreductase
17-OH Progestrone Androstenedione Testosterone
21 -Hydroxylase 21 -Hydroxylase
17β-Hydroxysteroid
Oxidoreductase
Deoxycorticosterone Deoxycortisol Estrone Estradiol
11β-Hydroxylase 11β-Hydroxylase
Corticosterone Cortisol
18-Hydroxylase
18-Oxidoreductase
Aldosterone
– Maternal androgens:
Causes of Congenital Adrenal Hyperplasia
• Although rare, 46,XX DSDs may be
• Enzyme deficiency:
drug-induced.
– 21-Hydroxylase deficiency
• Virilization of a female fetus may occur
– 11-Hydroxylase deficiency
if progestational agents or androgens
– 3-Beta-hydroxysteroid dehydroge-
are used during the first trimester of
nase deficiency
pregnancy.
• Maternal androgens:
– After the first trimester, these drugs
– Drug-induced (Progestational agents
cause only phallic enlargement with-
or Androgens)
out labioscrotal fusion.
– Functional ovarian tumors
– The incriminated drugs were for-
• Arrhenoblastomas
merly administered to avoid sponta-
• Krukenberg tumors
neous miscarriages in patients who
• Luteomas
had a history of habitual abortion.
• Lipoid tumors of the ovary
• Endocrine abnormality in the mother as
• Stromal cell tumors of the ovary
a source of virilizing hormones is even
rarer because these abnormalities, if ini-
tially present, usually prevent develop- • Management:
ment of a pregnancy. – These patients are treated early.
• Extremely rare, various functional ovar- – They should receive hormone replacement
ian tumors have caused virilization of a with corticosteroids.
female fetus. – Those with salt-losing CAH must be rec-
• These tumors include: ognized and treated with replacement
– Arrhenoblastomas therapy including corticosteroids and
– Krukenberg tumors minerlocorticoids.
– Luteomas – The surgical management is variable
– Lipoid tumors of the ovary depending on the extent of virilization and
– Stromal cell tumors of the ovary include:
31.10 Androgen Insensitivity Syndrome (Testicular Feminization Syndrome) 665
• Clitroplasty – Assays of genital skin fibroblasts elucidate

• Vaginoplasty depending on the level of the difference between receptor-negative
entry of the vaginal opening into the and receptor-positive types.
urogenital sinus. • Inheritance of this syndrome appears to be
• Labioplasty X-linked.
• Complete androgen insensitivity presents in
infancy only if the child has a shallow blind-ending
31.10 Androgen Insensitivity vagina, reflecting the lack of internal müllerian
Syndrome (Testicular development expected in an XY patient whose tes-
Feminization Syndrome) tes manufacture MIS at reference range levels.
• Inguinal hernias are common in testicular
• Androgen insensitivity syndrome affects feminization, and an occasional case is
males. detected during inguinal herniorrhaphy when
• There are two types of androgen insensitivity a gonad is present in the hernia and a fallopian
syndrome: tube cannot be seen (Figs. 31.23, 31.24, 31.25,
– Complete androgen insensitivity syndrome 31.26, and 31.27).
– Partial androgen insensitivity syndrome • Failure to identify an internal müllerian struc-
• Partial androgen insensitivity syndrome ture in a phenotypic female with an inguinal
results in ambiguous genitalia and there is no hernia should always raise the possibility of
consensus whether to raise a child with this testicular feminization.
syndrome as a male or female. • If not detected in this fashion, diagnosis usu-
• Complete androgen insensitivity syndrome ally is not made until puberty, when the patient
causes a genetically male to have an incom- presents with amenorrhea.
pletely developed and often blind ended • Although these characteristics are not noted
vagina, clitoris and breasts. early in life, these girls exhibit a body hair
• Patients with complete androgen insensitivity deficiency as they age, and their breasts,
syndrome are raised as females. although well formed, characteristically are
• Patients with complete androgen insensitivity deficient in stroma.
syndrome do not have a uterus or ovaries and • Despite a 46,XY karyotype and gonads with
are infertile. the typical appearance of testes (perhaps altered
• Syndromes of androgen insensitivity involve a similarly to those with cryptorchidism), a femi-
failure of the end organ (external genitalia and nine gender assignment is unquestionable
prostate) in a 46,XY gonadal male fetus to because of the completely feminine phenotype
respond to appropriately produced levels of and because end-organ failure prevents endo-
dihydrotestosterone (DHT), resulting in tes- crinologically produced masculinization.
ticular feminization. • Confirmation of the diagnosis is crucial
• Currently, the basic pathophysiology of the because the syndrome is associated with a sig-
lack of androgen effect on the genitalia is nificant incidence of gonadal malignancies.
understood more fully. • Malignant tumors are termed germinomas or,
– Some patients are receptor-negative; their more properly, seminomas because the tumors
cytosol receptors cannot bind DHT. arise in a testis.
– Another variant is receptor-positive, in – The youngest reported age of occurrence of
which receptors apparently permit DHT malignant tumor was 14 years.
binding, but DHT does not lead to – Overall frequency of gonadal malignancies
normal differentiation toward the male is approximately 6 %, with incidence rising
phenotype. to more than 30 % by age 50 years.
Figs. 31.23 and 31.24 Clinical photographs showing two female patients who had unilateral and bilateral inguinal
herniotomy and found to have complete androgen insensitivity syndrome
• Pubertal changes are induced easily with hor-

mone replacement, a requirement for all
patients following gonadectomy.
• Although a vaginoplasty later may be required,
many of these girls have an adequate vagina,
requiring no therapy or possibly only vaginal
dilation.
• Complete androgen insensitivity syndrome:
– This is seen in a 46XY male.
– CAIS occurs at a frequency of 1 in 20,000
to 1 in 64,000 male births.
– It results from failure of the end organ
(external genitalia and prostate) to respond
Fig. 31.25 A clinical photograph showing a female appropriately to dihydrotesteterone (DHT).
patient who was found to have complete androgen insen- – There are two subtypes of complete andro-
sitivity syndrome at the time of herniotomy. Note the nor- gen insensitivity syndrome:
mal looking testis in the hernial sac
• Receptor-negative type: These patients
are receptor negative and the main prob-
– Sertoli cell and Leydig cell tumors have lem is that their cytosol receptors cannot
been reported also. bind DHT.
– Tubular cell adenomas, also fairly frequent, • Receptor-positive type: These patients
have a potential for malignancy because are receptor positive but in spite of DHT
neoplastic transformation has been binding to its receptors it does not lead
reported. to normal differentiation of the external
• Disagreement exists on the best timing for genitalia toward the male phenotype.
gonadectomy. – This can be diagnosed based on assays of
– There are those who advocate delayed genital skin fibroblasts.
gonad removal after puberty. – Complete androgen insensitivity syndrome
– Others advocate early gonadectomy is inherited as X-linked.
because morbidity is minimal in a young – The gonads are symmetrical and exclu-
child. sively testicular tissue (seminiferous
Figs. 31.26 and 31.27 Clinical photographs showing a sitivity syndrome at the time of herniotomy. Note the nor-
hernia sac containing a normal looking testis in a female mal looking testis
patient who was found to have complete androgen insen-
tubules with no spermatogenesis and – It is important to establish the diagnosis in

increased numbers of Leydig cells). these patients because of the associated
– The Wolffian ducts develop in half of these risk of gonadal malignancies.
cases, while all Müllerian structures regress. – The diagnosis after puberty can be made by
– Phenotypically, patients are normal, tall and the presence of a male androgen and
hairless females with feminine external geni- gonadotrophin profile in a phenotypically
talia and a very short and shallow utricle. female patient.
– At the time of puberty, normal breasts – A prepubertal diagnosis is more difficult
develop due to peripheral conversion of and requires an hCG stimulation test and
testosterone to estrogen. PCR characterization of the androgen-
– Axillary and pubic hair is absent or scanty, receptor gene in DNA obtained from a
with slight vulval hair development. venous blood sample.
– Amenorrhoea is the rule. – The gonads are at low risk of malignancy
– A large number of patients with complete because of the cryptorchidism (2 %).
androgen insensitivity syndrome present – As the risk starts after puberty a gonadec-
with inguinal hernias and sometimes the tomy at puberty allows the spontaneous
diagnosis is made during inguinal hernior- onset of puberty to be followed by estrogen
rhaphy when a gonad is present in the her- therapy.
nial sac. – A prepubertal gonadectomy can be done if
– Failure to identify an internal Müllerian the condition is causing discomfort or her-
structure in a phenotypic female with an nia formation, or if the gene mutation has
inguinal hernia should always raise the not been characterized, to avoid virilization
possibility of testicular feminization syn- at the time of puberty.
drome (Figs. 31.28, 31.29, 31.30, 31.31, – Gonadoblastomas are the commonest
31.32, 31.33 and 31.34). malignant tumors in these patients.
– The other presentation of complete andro- – Other tumors include: Sertoli cell and Leydig
gen insensitivity syndrome is at puberty, cell tumors and tubular cell adenomas.
when the patient presents with – The management of these patients include
amenorrhea. and early or delayed gonadectomy.
– Despite a 46XY karyotype and gonads – The timing for gonadectomy is still
with the typical appearance of testes, these controversial.
patients are raised as females because of – There are those who recommend gonadec-
the completely feminine phenotype. tomy after puberty.
Figs. 31.28, 31.29, 31.30, and 31.31 Clinical photographs showing complete androgen insensitivity syndrome with
normal testes discovered at the time of herniotomy. The timing for gonadectomy is still controversial
– In contrast, others recommend early gonad- – In the Partial Androgen Insensitivity

ectomy because morbidity is minimal in a Syndrome (PAIS), the genitals can vary
young child. This also avoid the potential from mostly female to almost completely
risk of loss of some of these patients during male.
follow-ups. – Some people with PAIS think of them-
– Hormone replacement is important in these selves as girls/women, others regard them-
patients at puberty to induce secondary selves as boys/men, and some consider
female sexual characteristics. themselves mixed-gender.
– These patients may have a small vagina and – These patients demonstrate a spectrum of
a vaginoplasty may be required later in life. external genitalia ranging from:
– Others have an adequate vagina, requiring • Very feminine (Lubs syndrome)
no vaginoplasty or possibly only vaginal • Increasingly masculine (Gilbert-
dilation. Dreyfus syndrome)
• Partial (incomplete) androgen insensitivity • Most masculine (Reifenstein syndrome)
syndrome (PAIS) (Figs. 31.35 and 31.36): – They may present only with micropenis or
– An incomplete form of androgen insensi- cliteromegaly and causes a problem with
tivity also occurs. gender assignment.
Figs. 31.32, 31.33, and 31.34 Clinical intraoperative tes found at the time of inguinal herniotomy. Note also the
photographs showing a patient with testicular feminizing bilateral gonadectomy done early for two patients with
syndrome with bilateral intraabdominal undescended tes- testicular feminizing syndromes
Figs. 31.35 and 31.36 Clinical photographs of a patient with incomplete androgen insensitivity syndrome. Note the
slightly enlarged clitoris and also the normal looking vagina
– A diagnosis of incomplete androgen insen- – Exogenously administered androgens do

sitivity is suggested by elevated LH levels, not cause adequate virilization; therefore,
with reference range levels of plasma DHT incomplete androgen insensitivity raises
and 5-alpha-reductase activity in genital little question regarding the preferred sex
skin fibroblasts. with which to rear the child.
Figs. 31.37 and 31.38 Clinical intraoperative photographs showing clitroplasty in a patient with incomplete androgen
insensitivity syndrome
– Partial androgen insensitivity syndrome • Patients who are assigned as males will
results in ambiguous genitalia and there is require hormonal treatment to virilize
no consensus regarding whether to raise a their body.
child with this form as male or female. – Mild androgen insensitivity syndrome is
– An early gonadectomy and feminizing also described.
genitoplasty are recommended in infancy • This is a condition which mildly affects
by some authors. a genetic male’s ability to recognize
– In recent years the tendency has been to androgens.
postpone surgery until the child has • It is considered a form of androgen
expressed a clear gender preference and is insensitivity syndrome and is consid-
old enough to participate actively in deci- ered the least severe form.
sions about his/her medical treatment. • While men generally do not need any
– Nearly one third of patients develop a dys- specialized medical care related to this
germinoma or gonadoblastoma; therefore, form, mild androgen insensitivity syn-
gonadectomy becomes important as soon drome may result in gynecomastia and
as the diagnosis is recognized. hypospadias.
– The diagnosis of incomplete androgen • Removal of gynecomastia and repair of
insensitivity syndrome is suggested by: hypospadias can be performed.
• Elevated LH levels. • Men with mild androgen insensitivity
• Normal levels of plasma DHT. syndrome may have reduced fertility.
• Normal 5-alpha–reductase activity in
genital skin fibroblasts.
– These patients are managed with 31.11 Deficiency of MIS (Persistent
(Figs. 31.37 and 31.38): Müllerian Duct Syndrome)
• Early gonadectomy
• Clitroplasty • Persistent Müllerian duct syndrome (PMDS)
• Feminizing genitoplasty is also called hernia uterine inguinale.
• Hormonal replacement at puberty to induce • It is a rare condition and results from either a
female secondary sexual characteristics. complete failure of the testes to produce
31.11 Deficiency of MIS (Persistent Müllerian Duct Syndrome) 671
Müllerian Inhibiting Hormone or substance • At the time of herniotomy or orchidopexy, a

(MIH, MIS) or a failure of the Müllerian duct uterus and fallopian tube is found in the her-
to respond to its secretion. nial sac (Fig. 31.40).
• This is seen in males with normal 46XY • A vas deferens is presents bilaterally, usually
chromosomes. running close to the uterus.
• Both Wolffian and Müllerian ducts develop. • To avoid damage to the vas, care must be taken
• These patients have normal external genitalia at the time of Müllerian remnants excision.
and usually present with undescended testes • Sometimes, the vas deferens ends blindly.
or inguinal hernia (Fig. 31.39). • Abnormalities in the attachment of the epi-
• Isolated MIS deficiency is a rare syndrome didymis to the testis are also reported.
and usually does not present in the newborn • Appropriate surgical management attempts to
period because the genitalia appear to be those bring the testes into the scrotum based on the
of a male with undescended testes. rationale that testis tumors may occur later.
• The most common presentation is a pheno- • The incidence of malignancy is unknown.
typic male with an inguinal hernia on one side • A primary or staged orchidopexy is all that is
and an impalpable contralateral gonad. required.
• Inguinal hernia should be repaired when
present.
• Surgical removal of the Müllerian duct deriva-
tives is controversial, as malignancy in retained
Müllerian structures is extremely rare and the
potential fertility can be compromised by a surgi-
cal attempt to remove the Müllerian derivatives.
• The surgical management includes:
– Orchidopexy. This may necessitates divi-
sion of the uterus to lengthen the vas.
– A transverse testicular ectopia may be
associated with this condition. In this, both
testes are found on the same side.
– Excision of Müllerian remnants.
• This is still controversial
Fig. 31.39 A clinical photograph of a patient with nor-
mal looking external genitalia and undescended right tes- • This is not a simple procedure and care
tis who was found to have deficiency of MIS should be taken to avoid injury to the vas.
TESTIS UTERUS TESTIS

FALLOPIAN
of a patient with persistent
TUBES
Mullerian duct syndrome.
Note the presence of a
uterus, two fallopian tubes
and two testes but no
ovaries. This results from FALLOPIAN TUBES
deficiency of MIS
• Removal of Müllerian remnants is • The fetus is born with minimally virilized

unnecessary, since the remnants rarely external genitalia (pseudovaginal perineoscro-
produce symptoms and an extremely tal hypospadias).
rare risk of subsequent malignancy. • A 46,XY fetus with normal testes but lacking
the enzyme 5-alpha reductase in the cells of
the external genitalia and urogenital sinus can-
31.12 5-Alpha-Reductase not produce DHT.
Deficiency • Therefore, the fetus is born with minimally
virilized external genitalia (e.g., pseudovagi-
• This is an autosomal recessive condition nal perineoscrotal hypospadias), though the
caused by a mutation of the 5-alpha reductase fetus usually has a degree of phallic enlarge-
type 2 gene. ment, reflecting the direct action of
• 5-alpha reductase enzyme is important for the testosterone.
conversion of testosterone to dihydrotestester- • The fetus usually has a degree of phallic
one (DHT). enlargement as a result of the direct action of
testosterone.
• The striking feature in these patients is the
Deficiency of MIS (Persistent Müllerian Duct extreme virilization at puberty. This is most
Syndrome) likely caused by direct action of testosterone
• The karyotype is 46XY on the phallus. There will be increase in the
• Normal male external genitalia penile size as well as the muscle mass and a
• Results from complete failure of the tes- masculine voice.
tes to produce Müllerian Inhibiting • The main features that do not develop are the
Hormone or substance (MIH, MIS) or a ones depend on DHT (prostatic enlargement,
failure of the Müllerian duct to respond facial hair, acne).
to its secretion • There is a spectrum of 5-alpha-reductase defi-
• Both Wolffian and Müllerian ducts ciency which probably accounts for some of
develop. the variation in the phenotypes seen.
• Usually present with undescended testes • These patients are fertile with the ability to
or inguinal hernia have children.
• There is a uterus, two fallopian tubes • The diagnosis of 5-alpha-reductase deficiency
and two testes with two vas deference can be confirmed as follows:
but no ovaries – A patient with a 46XY karyotype.
• A transverse testicular ectopia may be – A high ratio of serum testosterone to
associated with this condition where DHT.
both testes are found on the same side
• The treatment is a primary or staged
orchidopexy 5-Alpha-Reductase Deficiency
• Excision of Müllerian remnants is • An autosomal recessive condition
controversial • Karyotype is 46XY
• Caused by a mutation of the 5-alpha
reductase type 2 gene
• They have normal testes but lacks the
• This is seen in males with a 46XY enzyme 5-alpha reductase
chromosomes. • 5-alpha reductase enzyme is important
• These patients have normal testes but lacks the for the conversion of testosterone to
enzyme 5-alpha reductase in the cells of the dihydrotestosterone (DHT)
external genitalia and urogenital sinus.
31.13 Gonadal Dysgenesis 673
– The surgical results of a masculinizing

• A high ratio of serum testosterone to operation in a mildly virilized infant are
DHT poor, and the burden to the child of grow-
• There is a spectrum of 5-alpha-reductase ing up with inadequate genitalia hardly
deficiency seems justified.
• The fetus is born with minimally viril- – Many authors recommend gonadectomy
ized external genitalia (pseudovaginal and feminizing genitoplasty in these
perineoscrotal hypospadias) patients.
• The striking feature is the extreme viril-
ization at puberty
• Many recommend that all patients with 31.13 Gonadal Dysgenesis
5-alpha reductase deficiency should be
raised as males. • Gonadal dysgenesis refers to a variety of con-
• Others recommend that only the most genital developmental disorders in which the
extremely virilized infant should be development of the indifferent embryonic
raised as males. gonads to differentiated gonads is inhibited.
• Many authors recommend gonadectomy • The gonads are usually hypoplastic and dys-
and feminizing genitoplasty in these functional with a complete germ cell
patients. deficiency.
• This loss leads to extremely hypoplastic
(underdeveloped) and dysfunctioning gonads
mainly composed of fibrous tissue, hence the
– During the first 60 days of life, infants name streak gonads—i.e., a form of aplasia in
experience a surge of LH that obviates the which the ovary is replaced by functionless
need to carry out HCG stimulation, which tissue.
may be useful to exaggerate the testoster- • The accompanying hormonal failure also pre-
one-to-DHT ratio characteristic of this vents the development of secondary sex char-
syndrome. acteristics in either sex, resulting in a sexually
– The normal testosterone-to-DHT ratio is infantile female appearance and infertility.
8–16:1, while patients with 5-alpha- • The group of gonadal dysgenesis disorders
reductase deficiency characteristically have includes:
a ratio greater than 35:1. – Pure gonadal dysgenesis (46,XX or 46,XY
– Urinary metabolites of testosterone and = Swyer syndrome)
DHT can be used to establish the – Mixed gonadal dysgenesis (mosaic
diagnosis. 45,X0/46,XY etc.)
– Cultured skin fibroblasts will demonstrate – Partial gonadal dysgenesis
decreased 5-alpha-reductase activity. – Turner syndrome
– Dysgenetic male pseudohermaphroditism
• Gender assignment and management: (DMP)
– Gender assignment is difficult in these – XX gonadal dysgenesis
patients because of the major virilization – Perrault syndrome
that occurs at puberty. • A streak gonad:
– Many recommend that all patients with – A gonads only consisting of fibrous tissue
5-alpha reductase deficiency should be and with no histological evidence of germ
raised as males. cells.
– Others recommend that only the most • A dysgenetic testis:
extremely virilized infant should be raised – A dysgenetic testis histologically demon-
as males. strates immature and hypoplastic testicular
tubules in a stroma characteristic of ovarian hypothalamic and pituitary glands to pro-

tissue but that lacks oocytes. duce adequate hormones.
– This stroma has the appearance of that seen – For this reason, in gonadal dysgenesis the
in streak gonads and may help to explain accompanying hormonal failure also pre-
the similarities of these syndromes. vents the development of secondary sex
– Dysgenetic testes have a high risk for characteristics in either sex, resulting in a
malignancy and can develop into malig- sexually infantile female appearance and
nant germ cell tumors such as dysgermino- infertility.
mas or gonadoblastomas. – Dysgenetic testes do not produce a suffi-
– In contrast, dysgenetic ovaries do not seem cient amount of testosterone in order to
to comprise an increased risk for malig- achieve a complete masculinization of the
nancy, as the existence of the GBY region genitals.
on the Y chromosome as well as the testes – Furthermore, AMH, which suppresses the
specific protein gene (TSPY) on the Y female anlage of the genitals is not
chromosome predispose for a malignant produced.
transformation – The clinical picture is heterogeneous.
• Embryology and pathogenesis: • Depending on the expression, the phe-
– The genetic sex is determined by the karyo- notype can be female or, in milder cases,
type, which is either XX or XY. the genitals can be male or only present
– The Y chromosome contains the SRY (sex with hypospadias.
determining region of the Y chromosome), – Gonadal dysgenesis will occur if there is an
which induces male sex development absence of both Müllerian inhibiting factor
during embryogenesis (The development and testosterone.
of the testes). • The absence of testosterone will result
– In the absence of the SRY or in the pres- in regression of the Wolffian ducts; nor-
ence of a second X chromosome, ovaries mal male internal reproductive tracts
develop. will not develop.
– This then determines the gonadal sex. • The absence of Müllerian inhibiting fac-
– The testes produce testosterone as well as tor will allow the Müllerian ducts to dif-
the anti-müllerian hormone (AMH), which ferentiate into the oviducts and uterus.
suppresses the development of the mülle- • The affected person will possess female-
rian ducts, precursors of the fallopian like internal and external reproductive
tubes, the uterus and the upper vagina. characteristics, lacking secondary sex
– The ovaries produce estrogens. characteristics.
– As a response to this hormone production • The genotype may be either 45,XO,
of the testes or ovaries, the phenotypic sex 46,XX or 46,XY.
develops. • The gonads are usually asymmetrical:
– As a result, if a gonad cannot express its – A dysgenetic testis on one side composed
sexual identity via its hormones—as in of disordered tubules, often sparse and
gonadal dysgenesis—then the affected per- abundant stroma
son, no matter whether their chromosomes – A streak gonad on the other side, composed
are XY or XX, will develop external female of ovarian stroma but with no oocytes.
genitalia. Internal female genitalia, primar- • The degree of virilization is variable but all
ily the uterus, may or may not be present patients have a vagina and a uterus, and most
depending on the etiology of the disorder. have a fallopian tube, at least on the side of the
– In both sexes, the commencement and pro- streak gonad.
gression of puberty require functional • Fertility has not been reported in patients with
gonads that will work in harmony with the MGD.
• The sex assignment varies, and factors to con- – Due to the numerous chromosomal aberra-
sider include: tions that can cause the Turner syndrome,
– Prenatal androgen exposure the clinical picture varies widely.
– Testicular function at and after puberty – Turner syndrome is characterized by:
– Phallic development • Streak gonads
– Gonadal location • Malformations of the internal organs
• Risk of malignancy: • Hypertrophy of the clitoris
– There is a risk of gonadal malignancy in • Hypospadias
these patients especially when a Y chromo- • The phenotype can be pure female or
some is present in the karyotype. male.
– These malignant tumors include: • In some patients, the function of
• Gonadoblastomas the gonads is partly or completely
• Seminomas maintained.
• Embryonal cell carcinomas – These patients can develop spontane-
• Turner syndrome: ous onset of puberty, menstruation or
– The classical Turner syndrome is charac- even pregnancy.
terized by a short stature, missing second- – Patients with a normal phenotype or
ary sex characteristics and webbed neck a spontaneous onset of puberty are
(lymphedema of the head and neck, often carriers of mosaicisms.
Lymphangiosis colli). – As patients with mosaicims usually
– It was first described by Otto Ullrich in do not have any stigmata, the diagno-
1930, a pediatrician from Munich. sis can be delayed and discovered
– In 1938, the American physician Henry accidently during investigation of
Turner described this syndrome which was infertility or recurrent abortions.
named after him. • Partial gonadal dysgenesis:
– It is also known as Ullrich-Turner syndrome – Partial gonadal dysgenesis can be classified
– The development of a normal female phe- as:
notype requires the presence of two func- • 46XY DSD
tioning X chromosomes. The loss of the • Sex chromosome DSD if there is mosa-
second sex chromosome (X or Y) takes icism (45X/46XY)
place postzygotically and depending on – Partial gonadal dysgenesis represents a
what cell stage the sex chromosome is lost, spectrum of DSD in which the gonads are
different chromosomal cell lines can be abnormally developed.
found concurrently which leads to the – Typically, at least one gonad is either dys-
development of mosaicisms. genetic or a streak.
– Turner syndrome is the most frequent form – The internal ducts vary according to the
of gonadal dysgenesis. associated gonads
– The incidence is estimated to be between – Although the degree of virilization varies,
1 in 3,000 and 1 in 2,500 live-born female all patients have a vagina and a uterus, and
infants. most have a fallopian tube, at least on the
– In Turner syndrome: side of the streak.
• 50 % of the patients have pure 45,X0 – Estrogen support is required if these
monosomy. patients are raised as females.
• 5–10 % have a duplication of the long – If the uterus remains in place, unopposed
arm of one of the X chromosomes estrogen can increase incidence of endo-
(46Xi(Xq)). metrial carcinoma; thus, these patients
• The rest are mosaicisms of 45,X0 with must be cycled with a combination of
one or more cell lines. estrogen and a progestational agent.
• Mixed gonadal dysgenesis (MGD): – As in all gonadal dysgeneses with

– Mixed gonadal dysgenesis (MGD) is the Y-chromosomes, there is a certain risk for
second most common cause of ambiguous malignancy, which is why gonadectomy is
genitalia in a newborn. indicated as early as possible.
– It is characterized by unusual and asym- • Dysgenetic male pseudohermaphroditism
metrical gonadal development. (DMP):
• A streak gonad is usually present on one – This term is used to describe patients with
side and a testis (usually dysgenetic) on bilaterally dysgenetic testes and incom-
the opposite side. plete virilization of the internal sex ducts
– A number of chromosomal karyotypes and external genitalia.
have been reported but most patients with • XX gonadal dysgenesis:
MGD have a mosaic karyotype, – This is a type of female hypogonadism in
45XO/46XY or 46,XX/46,XY. which no functional ovaries are present to
– It is assumed that the 45,X0 cell line causes induce puberty in an otherwise normal girl
the development of the streak gonads and whose karyotype is found to be 46,XX.
the 46,XY cell line is associated with the – The presence of nonfunctional streak ovaries
differentiated testis. is associated with low estrogen levels (hypoes-
– In MGD, 25 % of gonads, including streak trogenic) and high levels of FSH and LH.
gonads, can be expected to undergo malignant – Estrogen and progesterone therapy is the
change, most commonly to gonadoblastoma. recommended treatment.
– In addition to gonadoblastomas, semino- • Perrault syndrome:
mas and embryonal cell carcinomas may – In 1951, Perrault reported the association
develop. of gonadal dysgenesis and sensorineural
– Gender assignment for patients with MGD hearing loss.
remains controversial. • Management:
– The clinical picture of mixed gonadal dys- – Early gonadectomy is recommended in
genesis is heterogeneous. these patients.
• The external genitals can have a pheno- – The gender assignment for patients with
type ranging from female to male. DMP and MGD remains controversial.
• In most cases, the genitals are intersex- – There are those who recommend a male
ual with a hypertrophy of the clitoris or gender assignment for those patients who
hypospadias. are sufficiently virilized.
• As the AMH secretion is also affected to – Others recommend a female gender assign-
different degrees, variable constella- ment for patients with MGD because a
tions of the müllerian duct derivatives uterus and vagina are present always and
are possible. half of these patients have inadequate
• In most cases, the gonads have devel- external virilization.
oped asymmetrically (a streak gonads – Patients who are raised as females require
on one side and normal or dysgenetic estrogen supplements.
testes on the other side). The testis is – If the uterus remains in place, the unop-
usually intra-abdominal or inguinal. posed estrogen can increase the incidence
• In some cases, the streak gonads are of endometrial carcinoma and these
bilateral. patients should receive a combination of
• The testes have a normal histological estrogen and a progestational agents.
appearance before puberty. Sertoli and • Pure gonadal dysgenesis:
Leydig cells are present but germ cells – Pure gonadal dysgenesis is defined as the
are missing. absence of differentiated gonads, but with
normally developed internal and external appears to be associated with increased risk
genitalia. of gonadal malignancy.
– The karyotype is either 46,XX or 46,XY. – Histologically, there are streak gonads
• The 46XX type is usually transmitted composed of fibrous tissue or dysgenetic
by autosomal recessive inheritance, testes with Leydig and Sertoli cells but no
while the 46,XY type is transmitted by or only few germ cells, which have a malig-
X-linked inheritance. nancy potential of 25 %.
• The 46,XY type is named after G. J. – Patients with 46XY pure gonadal dysgen-
Swyer, the first person who described esis on the other hand carry a significant
the syndrome (Swyer syndrome). risk for malignancy. Nearly one third of
• A major part of the patients carries a patients develop a dysgerminoma or
mutation of the SRY gene which inhib- gonadoblastoma; therefore, gonadectomy
its the differentiation of the testes. should be done as soon as the diagnosis is
• Due to the lack of testosterone and confirmed.
AMH, the vagina and the uterus develop. – In 46,XX gonadal dysgenesis, the patient
– These patients are phenotypically females. usually has a homozygote or heterozygote
– They have bilateral streak gonads appear- mutation of the FSH receptor gene.
ing as ovarian stroma without oocytes. – An FSH receptor mutation causes a female
– Hypogonadism with elevated gonadotropin phenotype in the absence of secondary sex
levels is a characteristic finding in the characteristics.
affected patients. – The leading symptom is usually primary
– These patients are usually not recognized amenorrhea that results from a primary or
in the newborn period and they present at premature ovarian insufficiency.
puberty when they do not undergo normal – A homozygote FSH receptor mutation in
pubertal changes. patients with a female karyotype always
– The secondary sex characteristics fail to causes ovarian insufficiency and infertility,
develop, and or the menarche is absent while the heterozygote or the homozygote
(primary amenorrhea) form in patients with a male karoytype not
– Girls with Turner syndrome (45XO) may be always causes gonadal dysfunction or
detected earlier by noting the characteristic infertility.
associated anomalies of short stature, web- – Treatment of those with pure gonadal dys-
bing of the neck, and wide-spaced nipples. genesis is primarily limited to appropriate
– Swyer Syndrome (Also known as Pure Gonadal estrogen and progesterone replacement
Dysgenesis or XY gonadal dysgenesis): therapy.
• This is a type of hypogonadism in a per- – This is important for the maintenance of
son whose karyotype is 46,XY. bone density and for the induction of
• The person is phenotypically female female genital development.
with streak gonads, and if left untreated, – Pure gonadal dysgenesis syndromes can be
will not experience puberty. familial and call for genetic counseling.
• Such gonads are typically surgically • Turner syndrome appears sporadically,
removed as they have a significant risk suggesting a postzygotic error.
of developing tumors. • The 46XX type of pure gonadal
• These patients are treated with female ysgenesis is transmitted as autosomal
hormone replacement therapy. recessive.
– Neither Turner syndrome (45XO) nor the • The 46XY type is inherited as an
46XX type of pure gonadal dysgenesis X-linked recessive trait
31.14 Deficient Testosterone products. This however is available in special-

Biosynthesis ized centers only.
• During the newborn period, these patients
• Testosterone is produced from cholesterol. present as 46XY gonadal males with poor vir-
• Production of testosterone from cholesterol ilization and ambiguous genitalia.
involves five enzymatic steps, and defects • The genitalia in these patients respond to
have been identified at each step. exogenously testosterone.
• Of these five enzymes, three are shared with • This help differentiating them from 5-alpha
the adrenal glands, and their deficiency leads reductase deficiency which do not respond to tes-
to ambiguous genitalia and symptoms of tosterone but will respond to dihydrotestosterone.
CAH. These three enzymes are: • It is also important to treat those with CAH
– 20-alpha hydroxylase manifestations with steroid and mineralocorti-
– 3-beta-hydroxysteroid dehydrogenase coid replacement.
– 17-alpha hydroxylase • Genetic counseling is also important in these
• The other two enzymes occur only as part of patients as 17-alpha hydroxylase and 3-beta-
the normal testosterone biosynthesis and their hydroxysteroid dehydrogenase deficiencies
defects leads to ambiguous genitalia without are transmitted as autosomal recessive traits.
the symptoms of congenital adrenal • Other rare causes of testosterone production
hyperplasia. deficiencies include:
• These two enzymes are: – Leydig cell agenesis
– 17, 20 desmolase. – Leydig cell hypoplasia
– 17-ketosteroid reductase. – Abnormal Leydig cell gonadotropin
• The diagnosis of these enzyme deficiencies is receptors
possible by measuring the levels of precursor – Delayed receptor maturation
Cholesterol
20, 22 Desmolase
17β-Hydroxysteroid
17α-Hydroxylase 17-20 Desmolase Oxidoreductase
Pregnenolone 17-OH Pregnenolone Dehydroepiandrosterone Androstenediol
3 β-Hydroxysteroid 3 β-Hydroxysteroid 3 β-Hydroxysteroid 3 β-Hydroxysteroid

Dehydrogenase Dehydrogenase Dehydrogenase Dehydrogenase
17β-Hydroxysteroid
17α-Hydroxylase
Progestrone 17-20 Desmolase Oxidoreductase
17-OH Progestrone Androstenedione Testosterone
21 -Hydroxylase 21 -Hydroxylase
17β-Hydroxysteroid
Oxidoreductase
Deoxycorticosterone Deoxycortisol Estrone Estradiol
11β-Hydroxylase 11β-Hydroxylase
Corticosterone Cortisol
18-Hydroxylase
18-Oxidoreductase
Aldosterone
31.15 Ovotestis Disorders of Sexual Development 679
31.15 Ovotestis Disorders – Although some cases of ovotestis DSD are

of Sexual Development diagnosed in the newborn period, only
20 % are diagnosed prior to age 5 years.
• This refers to a rare condition in which the his- – Most cases of ovotestis DSD are diagnosed
tology of a gonad contains both ovarian and in the pubertal period when the young male
testicular tissues (Figs. 31.41 and 31.42). begins to experience feminization.
• A diagnosis of Ovotestis-DSD is based solely – Inguinal hernia and cryptorchidism are
on the presence of ovarian and testicular tissue common in these patients.
in the gonad and not on the characteristics of • The peripheral karyotype is also variable in
the internal and external genitalia. these patients and include:
• This was formerly known as true – 46,XX ovotesticular DSD. This is the most
hermaphroditism. common karyotype, seen in 60–80 % of
• They account for less than 10 % of DSD cases. patients.
• The appearance of the genitalia varies widely – 46, XY ovotesticular DSD. This karyotype
in this condition. is found in about 10–15 % of patients.
• Although ambiguity is the rule, the tendency – 46,XX/46,XY peripheral karyotype
is toward masculinization. • A translocation of the gene coding for HY antigen
• Presentation: from a Y chromosome to either an X chromosome
– In the neonatal period, these patients usu- or an autosome presumably explains the testicular
ally presents with ambiguous genitalia. material in a patient with a 46,XX karyotype.

intraoperative
photograph of a patient VAS DEFERENCE
with ovotesticular
DSD. Note the
ovotestis, the vas FALLOPIAN
deference and TUBE
Fallopian tube
OVOTESTIS
VAS DEFERENCE

of a patient with FALLOPIAN
ovotesticular DSD. Note TUBE
the presence of a
fallopian tube and a vas
• More problematic is how a patient with a • The anatomical location of these gonads is
46,XY karyotype can have ovarian tissue, variable:
given that two X chromosomes are believed to – The ovotestis tends to be anatomically
be necessary to normal ovarian development. located in:
Possibly, unidentified XX cell lines are pres- • A normal ovarian position
ent in these patients. • In the labioscrotal fold
• The gonads in these patients may be: • In the inguinal canal
– Ovotestis on both sides • At the internal inguinal ring
– A combination of an ovary on one side and – Ovaries, when found, can occupy the nor-
a testis or ovotestis on the other side. mal abdominal position, although they may
– Ovotestes on both sides are the most fre- occasionally be found at the internal ingui-
quent gonad present (60 %), followed by nal ring.
the ovary and then the testis (9 %). • Interestingly, ovaries occur more com-
– When an ovotestis is present, one third of monly on the left side than the right.
the patients exhibit bilateral ovotestes. • The testes are usually found in the scro-
– A testicle, when present, is more likely to tum, although they can be found at any
exist on the right (57.4 %), and an ovary, level along the path of embryonic
when present, is more commonly seen on descent from abdomen to scrotum, fre-
the left (62 %). quently presenting as inguinal hernias.
– A palpable gonad is present in 61 % of – Many patients with ovotesticular disorder
patients; of these, 60 % are found to be an of sexual development have a uterus.
ovotestis. – Internal duct development usually corre-
– In 80 % of patients with ovotestes, testicu- sponds to the adjacent gonad so that:
lar and ovarian tissues are aligned in an • Müllerian duct structures are usually
end-to-end fashion, emphasizing the need seen on the gonad side(s) not containing
for a long longitudinal biopsy. testicular tissue.
– In 20 % of patients with ovotestes, testicu- • Wolffian duct structures are usually
lar tissue is found in the hilar region of the seen on the gonad side(s) containing
gonad, reemphasizing the need for an ade- functioning testicular tissue.
quate and deep biopsy. • Ovotestes are usually made up of ovarian part
– An ovary, when found, is situated most and testicular part with connective tissue
commonly in the normal anatomic intra- between then. This is important surgically
abdominal position, and extremely rare an when separating the ovarian components from
ovary can be found in the hemiscrotum. the testicular components. However, on rare
– The least common gonad in ovotesticular occasions, it is difficult to separate the two.
DSD is the testis; when present, a testis is • Most patients with ovotestes DSD are reared
found approximately two thirds of the time as males due to the size of the phallus but male
in the scrotum, emphasizing that normal tes- reproductive potential in these individuals is
ticular tissue is most likely to descend fully. rare.
– Ovotestes may present with either a fallo- • This is not the case in those who are assigned
pian tube or a vas deferens but usually not a female gender with 46,XX chromosomes
with both. who have fertility potential.
– If a fallopian tube has a fimbriated end, the • They also have varying degrees of labioscrotal
end is closed in most patients, perhaps confusion and/or hypospadias which needs
tributing to the usual lack of fertility. correction.
– Although fertility is rare in this setting, it • Most cases of ovotesticular DSDs are diag-
has been reported. nosed during the adolescent period and
– Gonadal tumors also are rare but have been because of functioning normal ovarian tissue,
reported. most of them experience breast development
31.15 Ovotestis Disorders of Sexual Development 681
at puberty, and approximately two-thirds of of gonadotropin or clomiphene

those with a 46,XX peripheral karyotype citrate administration.
menstruate. – An estradiol response to gonadotropin
• Patients with ovotestes DSD are at risk of stimulation is a reliable test to differ-
gonadal tumors which occur in 2.6 % of the entiate ovotesticular disorder of sexual
cases. development from other disorders.
– The testis or testicular part of an ovotestis is – Radiological evaluation:
likely to be dysgenetic with a risk of devel- • A scrotal ultrasonography is used to
oping dysgerminomas, seminomas, gonad- detect occult gonads.
oblastomas, and yolk sac carcinomas. • A genitogram is used to evaluate the
– The risk is more in those with 46,XY structure of the urethra and to confirm
karyotype. the presence of a vagina and uterus
– Benign tumors, including mucinous cyst- (Fig. 31.43).
adenomas, benign teratomas, and Brenner • An intravenous pyelogram is important
tumors, have also been reported in these to rule out any associated urinary tract
patients. anomalies.
• Investigations: • Abdominal and pelvic ultrasonography,
– Chromosomal analysis CT scan, or MRI are useful in delineat-
– Hormonal evaluation ing the gonads and duct structures.
• Serum 17-hydroxyprogesterone: • Management:
– Patients with ovotesticular DSD have – The main point in the management of these
normal levels of this hormone which patient is gender assignment.
differentiate them from those with – This must take in consideration two main
congenital adrenal hyperplasia. points:
• Basal and stimulated serum androgens: • The potential for normal sexual
– The presence of functional testicular function
tissue can be determined with the use • The potential for future reproductive
of a human chorionic gonadotropin function
(HCG) stimulation test. – It is important to establish histological con-
– In this test, basal levels of testoster- firmation with a gonadal biopsy which can
one, dehydroepiandrosterone sulfate, be done via a laparotomy or Laparoscopically.
androstenedione, and dihydrotestos- – Surgery in these patients should be planned
terone (DHT) are measured. with the previous two goals in mind and
– HCG (3,000–5,000 IU/m2/d IM) is conservative gonadal surgery is the proce-
then administered for 5 days. dure of choice.
– On the day 6, the serum hormone – Ovotestes frequently can be separated into
levels tests are repeated. ovarian and testicular components and par-
– A rise in serum testosterone demon- tial resection of ovotestes is feasible in a
strates the presence of functioning
Leydig cells.
– Elevated testosterone precursors may
suggest a specific defect of testoster-
one synthesis.
– Failure of testosterone to reduce to
DHT may suggest a 5-alpha reduc-
tase deficiency.
• Basal and stimulated estrogen levels:
– The presence of functional ovarian Fig. 31.43 A genitogram showing a normal looking
tissue can be determined with the use vagina in a patient with ovotesticular DSD
large number of these patients which • Excision of intra-abdominal testis or

should be guided by intraoperative histo- streak gonads in those with Y
logic confirmation (Fig. 31.44). chromosome-DNA because of increased
– It allows preservation of gonadal tissue risk of malignant transformation.
concordant with sex of rearing, and removal • Excision of wolffian structures and tes-
of all discordant tissue. ticular tissue if the patient has been
– The ovarian tissue can be preserved in peo- given a female gender assignment.
ple who are given a female sex assignment. • Excision of Müllerian structures and
Frequently, these patients demonstrate nor- ovarian tissue if the patient has been
mal ovarian function and potential for given a male gender assignment.
reproduction. • Orchiopexy to treat an undescended tes-
– The aim is to preserve the gonadal tissue tis in a patient with male gender
that is concordant with sex of rearing, and assignment.
excision of all other tissue. • Clitoral recession, vaginoplasty, and
– Cystoscopy may be used to determine the labioscrotal reduction are necessary for
position of entry of the vagina into the ure- people with ovotesticular DSD who are
thra or urogenital sinus. given a female sex assignment.
– Prophylactic gonadectomy should be con- • These feminizing procedures should be
sidered in those who manifest signs of vir- performed as early as possible as a
ilization or are at an increased risk of 1-stage procedure.
gonadal malignancy. • Correction of penile deviation and
– Hormone replacement might be required hypospadias should be done in those
for those with pubertal delay. given a male gender assignment.
– The following operative procedures are
indicated in patients with ovotestes DSD
depending on the sex of rearing: 31.16 Other Rare Disorders
of Sexual Development
17β-Hydroxysteroid dehydrogenase deficiency:

• This condition is characterized by impaired
androgen and estrogen synthesis in both males
and females.
• The end result is:
– Pseudohermaphroditism/undervirilization
in males.
– Excessive virilization of females.
Aromatase deficiency:
• Aromatase is the enzyme that catalyzes con-
version of androgens into estrogens.
• As a result of this enzyme deficiency, there
will be androgen excess and estrogen
deficiency.
• This results in inappropriate virilization of
females.
• They have normal female external genitalia.
Fig. 31.44 A clinical intraoperative photograph of a
patient with ovotesticular DSD. Note the presence of an • They may have cliteromegaly.
ovotestis on this side • These female patients can present:
31.16 Other Rare Disorders of Sexual Development 683
– During childhood and adolescence with • The chromosomal karyotype is 47, XXX.
cystic ovaries • It is a common condition affecting 1 in 1,000
– At puberty with: females.
• Primary amenorrhea • It is a benign condition and generally does
• Failure of breast development not cause health issues or abnormal
• Virilization development.
• Hypergonadotrophic hypogonadism
Aromatase excess syndrome: Aphallia:

• This is also called familial hyperestrogenism. • This is a rare congenital condition where a
• In this condition, there is excessive estrogen male is born without a penis or where a female
production. is born without a clitoris.
• It is seen in males and females. • It should not be confused with intentional or
• In males, it will result in feminization with- accidental amputation of the genitalia.
out pseudohermaphroditism.
– A normal male external genitalia at birth. Aposthia:
– Female secondary sexual characteristics • A congenital defect where a male is born
at puberty. without a foreskin.
• In females, it will lead to hyperfeminization.
Diphallia:
Klinefelter syndrome: • This is also known as penile duplication,
• This condition is seen in males born with at diphallic terata, and diphallasparatus.
least one extra female chromosome. • This is extremely rare.
• It is also called XXY syndrome. • It is characterized by a male born with two
• The chromosomal karyotype is 47, XXY. penises.
• Though the most common chromosomal vari- • The penises may be side by side or one on top
ation is 47, XXY, other variations may also be of the other.
48, XXXY or 49, XXXXY. • The penises may be of equal size or with one
• It is a common occurrence, affecting 1 in 500 penis being distinctively larger than the
to 1,000 men. other.
• While some men may have no issues related to • Both penises may be suitable for urination and
the syndrome, others may experience: intercourse.
– Gynecomastia • Men with diphallia may be sterile.
– Micropenis
– Cognitive difficulties Micropenis:
– Hypogonadism • This is also known as microphallus.
– Reduced fertility/infertility • It is defined as a penis that measures 3 in.
– Little or no facial hair. (7.62 cm) or less in length when erect.
• Testosterone therapy may be pursued by men • It is a common condition, occurring in 1 in
who desire a more masculine appearance and 200 men.
those with gynecomastia may opt to undergo a • Micropenis may be the result of underviriliza-
reduction mammoplasty. tion during fetal development or may be
• Men who wish to father children may be able caused by an underlying intersex condition,
to do so with the help of IVF. such as mild androgen insensitivity syndrome,
partial androgen insensitivity syndrome, or
Triple X syndrome: Klinefelter syndrome.
• A condition that occurs in a female born with • It may also be considered a natural variation
an extra female chromosome. of penis size.
ATROPHIC
TESTIS
ATROPHIC
TESTIS
Fig. 31.45 A genitogram showing a double vagina
• While the majority of men have no issues with ATROPHIC

having a micropenis, some may opt to use a TESTIS
prosthetic penis or undergo penile enlarge-
ment to increase the size of their penis.
Uterus didelphys:
• This is also known as double uterus.
• It is seen in a female born with two uteri.
• It is often accompanied by two vaginas
Figs. 31.46 and 31.47 Clinical intraoperative photo-
(Fig. 31.45). graphs showing unilateral and bilateral atrophic testes.
• This is a benign condition and females with These are usually secondary to intrauterine torsion of tes-
uterus didelphys usually have normal sex lives tes. Note the presence of a vas
and pregnancies.
Bilateral vanishing testes:

• ‘Bilateral vanishing testes’ implies absent
gonads that could be due to mutation, expo-
sure to a teratogen, or bilateral torsion (Figs.
31.46 and 31.47).
• The karyotype is typically 46,XY.
• The phenotype shows a male with unde-
scended testes.
• Laparoscopy can detect rudimentary cord
structures with no recognizable testicular tis-
sue histologically.
• These patients will require androgen replace-
Fig. 31.48 A clinical photograph showing cliteromegaly.
ment and testicular prostheses. Note the normal external genitalia
• Embryonic testicular regression syndrome is a
variant of bilateral vanishing testes in which
the testicular function is lost early in embry- Clitoromegaly:
onic life. This results in individuals with • A clitoris that is considered larger than aver-
ambiguous genitalia. age (Fig. 31.48).
Further Reading 685
• While clitoromegaly may be a symptom of an • Patients may present at birth with a fully
intersex condition, it may also be considered a female phenotype, ambiguous genitalia, or
normal variation in clitoris size. only mild genital defects such as micropenis
• Clitoromegaly causes no health issues. and hypospadias.
• Surgical reduction of the clitoris or its com- • Upon puberty, sexual development is either
plete removal may be performed to normalize impaired or fully absent.
the appearance of the genitalia.
• While female genital mutilation is outlawed in Pseudovaginal perineoscrotal hypospadias
many countries, reduction or the removal of (also known as PPSH):
the clitoris in cases of clitoromegaly are gen- • This is a form of ambiguous genitalia which is
erally exempt, despite the fact that it is a non- characterized by:
therapeutic and sexually damaging surgery. – A phallic structure that is smaller than a
• Clitoromegaly may also be caused by females penis but larger than a clitoris
using testosterone or anabolic steroids for pur- – A chordee
poses related to female to male gender transi- – Hypospadias
tion or bodybuilding. – A shallow vagina
Combined 17α-hydroxylase/17,20-lyase deficiency:

• A condition which presents as a combination
of the symptoms of congenital adrenal Further Reading
hyperplasia and isolated 17, 20-lyase
1. Aaronson IA. True hermaphroditism. A review of 41
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3. American Academy of Pediatrics. Timing of elective
insensitivity syndrome.
surgery on the genitalia of male children with particu-
• It is extremely rare, with only one verified lar reference to the risks, benefits, and psychological
case having been reported. effects of surgery and anesthesia. Pediatrics. 1996;97:
• A biological male presented with tall stature, 590–4.
4. Barthold JS. Disorders of sex differentiation: a pediat-
a heightened risk of osteoporosis, and
ric urologist’s perspective of new terminology and
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5. DeVries ALC, Doreleijers TAH, Cohen-Cettenis
Isolated 17,20-lyase deficiency: PT. Disorders of sex development and gender identity
outcome in adolescence ande adulthood: understand-
• A condition that is characterized by an either
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• It results in partial or complete feminization sexuality. Guidelines for dealing with persons with
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• A condition solely affecting biological males adrenal hyperplasia. Endocr Dev. 2014;27:203–9.
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opment. Curr Opin Endocrinol Diabetes Obes. ence. Int J Urol. 2011;18(3):231–6.
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12. Hughes IA. Disorders of sexual differentiation. Horm talia. Semin Perinatol. 1992;16(6):365–8.
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13. Hughes IA, Houk C, Ahmed SF, Lee PA. Consensus Surgical management of the intersex patient: an over-
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Index
A clinical photographs, 669

Abdomino-scrotal hydrocele, 410, 413 diagnosis, 669, 670
Acute epididymitis, 560, 610–612 symptoms, 638, 668
Acute scrotum treatment, 670
acute epididymitis, 610–612 pathophysiology, 665
bacterial epididymitis, 611 Angiomyolipoma
causes, 613–614 classification, 157–158
common causes, 601 clinical features, 158
differential diagnosis, 601 diagnosis, 158–159
idiopathic scrotal edema, 612–613 histopathology, 157
orchitis, 610 incidence, 156–157
testicular torsion, 601–608 treatment and prognosis, 159
testicular trauma, 613 Antenatal hydronephrosis
torsion of testicular appendices/epididymal antibiotic prophylaxis, 68
appendage bilateral, 67–68
appendix testis, 608 diuretic renography, 67
clinical features, 609 fetal, 65, 66
clinical investigations, 609–610 infants, management of, 67
diagrammatic representation, 608, 609 moderate and mild unilateral, 68
embryology, 609 pathological causes, 66
epididymal appendix, 608 postnatal radiology, 66–67
incidence, 608 risk of, 65–66
treatment, 609–610 severe unilateral, 68
Adrenal rests, 588 severity, 66, 67
AIS. See Androgen insensitivity syndrome (AIS) surgical management, 68–69
Alagille syndrome, 180 systematic review, 66
5-Alpha reductase deficiency (5ARD), 638, 656, Tc99m MAG3, 67
672–673 ultrasonography, 66
Ambiguous genitalia. See Disorder of sex VCUG, 67
development (DSD) vesicoureteral reflux, 65
Amyand’s hernia, 406, 407 Anti-Müllerian hormone (AMH) effect, 287–291, 530,
Anatomical/gonadal sex, 638 531, 538, 643, 648, 654–655, 674, 676, 677
Androgen insensitivity syndrome (AIS) Aphallia, 683
CAIS Aposthia, 683
amenorrhea, 667 Ascent testis, 531, 534
inguinal hernias, 666–669 Aspiration and irrigation procedure, 519–522
receptor-negative type, 666 Autosomal dominant polycystic kidney disease
receptor-positive type, 666 (ADPKD), 8, 10, 18, 179
symptoms, 638, 665 Autosomal recessive polycystic kidney disease
diagnosis, 665, 667 (ARPKD), 8, 10, 12, 18, 179
gonadectomy, 666–668
hormone replacement, 668
malignant tumors, 665–667 B
mild androgen insensitivity syndrome, 670 Bacterial epididymitis, 611
PAIS Bardet-Biedl syndrome, 621–623, 625

A.H. Al-Salem, An Illustrated Guide to Pediatric Urology, DOI 10.1007/978-3-319-44182-5
688 Index
Bartter syndrome, 274, 282 Mitchell technique, 357

Beckwith-Wiedemann syndrome (BWS), 105, 112, 180 modified Bryant’s traction, 357
Bell-clapper deformity, 553, 554, 603 modified Buck’s traction, 357
Berdon syndrome. See Megacystis-microcolon-intestinal MSRE, 358–359
hypoperistalsis syndrome (MMIH syndrome) Mummy wrapping, 357
Bilateral nonpalpable testes, 529–530 pelvic osteotomies, 357
Bilateral vanishing testes, 684 postoperative complications, 360
Bladder prevalence, 350
abnormalities radiological evaluation, 353
agenesis, 32 repair, 352–353
clinical photographs, 22, 27 risk factors, 350
cloacal exstrophy, 22, 25, 26, 28 surgical technique, 355–356
diverticulum, 26, 27, 30, 31 treatment goals, 352
duplication, 32 Bosniak classification, 11
ears, 30, 32 Branchio-oto-renal (BOR) syndrome, 175, 180
megacystis, 32–34 Busse’s hernia, 405, 406
persistent urachus, 26, 28–31 Byer’s flaps, 464, 465, 471
septation, 32
Bladder exstrophy-epispadias
anatomical defects C
bladder exstrophy, 339–340 CAH. See Congenital adrenal hyperplasia (CAH)
cloacal extrophy, 340 CAIS. See Complete androgen-insensitivity
epispadias, 340 syndrome (CAIS)
exstrophy variants, 341 Canal of Nuck hydroceles, 412
cloacal exstrophy (see Cloacal exstrophy) Children’s Oncology Group staging system, 580, 581
congenital abnormalities, 337 Chordee without hypospadias, 454
definition, 337 Circumplast circumcision, 488, 489, 494
embryology, 341–342 Clear cell sarcoma of the kidney (CCSK)
epispadias clinical features, 140
complete, 342, 343 definition, 138
etiology, 343–344 diagnosis, 140
female, 348–349 histopathology, 140–141
glanular, 343, 344 pathophysiology, 139–140
incidence, 342 prognosis, 142
isolated, 342 treatment, 141–142
penile, 344, 345 Clitoromegaly, 39, 40, 625, 652, 658, 684–685
penopubic, 344, 345 Cloacal anomalies
prognosis, 349–350 associated anomalies
surgical repair, male, 347–351 anorectal malformations, 383
treatment, 345–347 Currarino triad, 383
exstrophy (see Bladder exstrophy) genital anomalies, 384
incidence, 338 sacrum and spine anomalies, 383
manifestation, 338 tethered cord, 383
musculoskeletal defects, 341 urogenital anomaly, 383
neurologic defects, 341 vaginal/uterine septation, 384
phallus, 339–340 classification
staged repair, 338 long common channel, 384
Bladder extrophy short common channel, 384
associated anomalies, 354–355 clinical features
classic bladder, 353–354 abdominal distension, 384, 385
cloacal exstrophy, part of, 350–353 Currarino triad, 385
diagnosis, 351 distended vagina, 385
management and evaluation hydrocolpos, 384, 385
antibiotics, 356 hydronephrosis, 385
bladder augmentation, 359 persistent cloaca diagnosis, 384, 385
bladder neck reconstruction, 359 common single perineal opening, 381, 382
cardiac echo, 356 definition, 381
CPRE, 357 incidence, 381
early bladder closure, 357 investigations
latex precautions, 356 abdominal ultrasonography, 386
Index 689
cystoscopy and vaginoscopy, 386, 387 prevalence, 360, 415

distal loopogram, 386, 387 prognosis, 371
echocardiography, 386 skeletal changes, 363
MRI, 386, 388 surgical reconstruction, 370–371
sacral ratio calculations, 386 surgical repair, 368–370
sacrum plain radiography, 386 urinary incontinence management, 371
spinal ultrasonography, 386 Cobb’s collar, 427
spine plain radiography, 386 Combined 17α-hydroxylase/17,20-lyase
management deficiency, 685
abdominal approach, 387–389 Communicating hydroceles, 411, 412
bowel, 390 Complete androgen-insensitivity
colostomy, 387–390 syndrome (CAIS)
cystoscopy and vaginoscopy, 390 amenorrhea, 667
dilated sigmoid colon, 389 inguinal hernias, 666–669
goals, 387 receptor-negative type, 666
hydrometrocolpos, 388 receptor-positive type, 666
intermittent catheterization, 390–391 symptoms, 638, 665
laparotomy, 388, 389 Complete Primary Repair of Exstrophy (CPRE), 357
Mitrofanoff procedure, 390, 391 Congenital adrenal hyperplasia (CAH)
prognostic factors, 390 3-beta-hydroxysteroid dehydrogenase
PSARVUP, 387–388 deficiency, 663
stages, 387–388 biochemical defect, 659
surgical treatment, 388 clinical photographs, 636, 637, 660, 661
total urogenital mobilization, 389 diagnosis, 660
Cloacal exstrophy, 532, 535 11-hydroxylase deficiency, 663
anomalies, 360, 361 21-hydroxylase deficiency, 659, 660, 662–663
abdominal wall musculature incidence, 660
deficiency, 418 maternal androgens, 664
bladder augmentation, 418–420 metabolic defects, 660
double and absent appendix, 418 mineralocorticoteroids, 660
gastrointestinal duplications, 418 prenatal diagnosis, 660
lower extremity, 418 salt-wasting nephropathy, 660
short bowel syndrome, 418 symptoms, 638
spinal and skeletal, 417–418 treatment, 664–665
tallipes equinovarus, 418 urogenital sinus, 660–662
upper urinary tract, 418 Congenital anomalies of the kidney and urinary tract
urological malformations, 418 (CAKUT), 1–2
anorectal agenesis, 362, 417 Congenital megaureter
associated anomalies clinical presentation, 225
cardiovascular and pulmonary, 365 complications, 234
gastrointestinal, 365 dilated ureter, 217
mullerian and testicular, 365 investigations and diagnosis, 225–231
neurospinal, 365 non-refluxing/non-obstructed megureter
spinal and skeletal, 364 primary megaureter, 218, 222, 225
upper urinary tract, 365 secondary megaureter, 219, 222
clinical features, 366–367 obstructed megaureter
ileo-cecal region, 415, 416, 418–419 primary megaureter, 219, 220, 222–224
prolapsed bowel, 420 secondary megaureter, 219, 220, 222
prolapsing terminal ileum, 419 refluxing megaureter
ureteric catheters, 420 primary megaureter, 218, 219, 222, 223
complications, 372 secondary megaureter, 219, 222
components, 415, 416 refluxing/obstructed megaureter
embryology, 416–417 primary megaureter, 222, 224–225
etiology, 363, 415 secondary megaureter, 219, 222
genitalia, 415 treatment and prognosis, 231–234
management, 366–368, 419–421 VUR, 218, 234
OEIS complex, 360 Congenital mesoblastic nephroma (CMN).
omphalocele absence, 417 See Mesoblastic nephroma
pathogenesis, 363–364, 415 Congenital obstructing posterior urethral membrane
prenatal diagnosis, 364 (COPUM), 425
690 Index
Congenital ureteral anomalies fusion, 12, 13

clinical features, 188 horseshoe kidney, 12, 14–15
duplex (duplicated) system hypoplasia, 6–7
abdominal and pelvic ultrasound, 194–195 multicystic kidney, 8–10
bifid ureters, 191 polycystic kidney disease, 8, 10
classification, 192–193 supernumerary kidneys, 7
clinical features, 193 normal embryology, 2–4
complete ureteral duplication, 189, 191–192 penis and urethra, in males
complication, 192 apenia, 33
CT scanning, 192 congenital urethral stricture, 35, 36
CT urography, 195 diphallia, 33–34
incomplete ureteral duplication, 189, 191 epispadias, 36, 39–40
IVU, 193, 194 hypospadias, 35–38
micturating cystourethrography, 195 megalopenis, 34, 35
MR urography, 195, 196 micopenis, 33–34
nuclear scan, 195 posterior urethral valves, 35, 37
scintigraphy, 192 ureter
treatment and prognosis, 195–197 duplication of, 18–20
unilateral or bilateral, 189, 190 ectopic ureteral orifice, 20
ectopic ureter mega-ureter, obstruction, 21–22, 25, 26
association with, 197 ureteral atresia, 18, 19
bilateral single-system ureteral ectopia, 197 ureterocele, 19, 21
clinical features, 199–200 ureteropelvic junction, 20–23
diagnosis, 200 Coronal hypospadias, 458, 459
duplicated renal collecting system, 197 Cryptorchidism. See Undescended testes
embryology and pathophysiology, 198–199 Cystic dysplasia, 179–181, 589, 590
in females, 197, 198 Cystic partially differentiated nephroblastoma (CPDN),
in males, 197, 198 165–168
surgical treatment, 200–202 Cystourethroscopy, 265, 433
Weigert-Meyer rule, 197
etiology, 187–188
investigations and diagnosis, 188–189 D
mega ureter, 212–215 Denys-Drash syndrome, 103, 104, 109, 112,
ureterocele (see Ureterocele) 113, 639, 648
VUR, 208–212 Desmopressin (DDAVP), 127
Congenital urological malformations Detrusor external sphincter dyssynergia (DSD), 302
bladder Detrusor hyperreflexia with impaired contractility
agenesis, 32 (DHIC), 303
clinical photographs, 22, 27 Detrusor sphincter dyssynergia with detrusor
cloacal exstrophy, 22, 25, 26, 28 hyperreflexia (DSD-DH), 298, 302–303
diverticulum, 26, 27, 30, 31 Dimercaptosuccinic acid (DMSA), 33, 82, 183, 195,
duplication, 32 205, 242, 255, 256, 263, 316, 329, 433
ears, 30, 32 Diphallia, 33, 34, 36, 683
megacystis, 32–34 Direct inguinal hernia, 405
persistent urachus, 26, 28–31 Disorder of sex development (DSD)
septation, 32 Aaronson’s classification, 650
CAKUT, 1–2 AIS, 638
ESKD, 1 aphallia, 683
female external genitalia aposthia, 683
clitoral hypertrophy, 39–40 5ARD, 638, 672–673
distal urethral stenosis, 36–37 aromatase deficiency, 682–683
female epispadias, 37, 39 aromatase excess syndrome, 683
labial fusion, 37 17β-hydroxysteroid dehydrogenase deficiency, 682
urethral prolapse, 40–41 bilateral vanishing testes, 684
kidney CAH (see Congenital adrenal hyperplasia (CAH))
agenesis, 5–6 clinical investigations, 653–655
crossed fused renal ectopia, 15–17 clinical photographs, 635
cysts, 11–12 clitoris, dermoid cyst, 637
dysplasia, 8–10 clitoromegaly, 684–685
ectopic kidney, 12, 13, 17–18 cloacal exstrophy, 636
Index 691
combined 17α-hydroxylase/17,20-lyase DYG (The Double Y Glanuloplasty) procedure, 467

deficiency, 685 Dysgenetic male pseudohermaphroditism (DMP),
deficient testosterone biosynthesis, 678 673, 676
definition, 636 Dysgenetic testis, 343, 531, 533, 646–648, 650, 655,
diagnosis, 653–655 673–674, 676, 677
diphallia, 683
gonads disorders, 650, 651
phenotype disorders, 650 E
sex chromosomes disorders, 650 Ectopic kidney, 4, 16–18, 72, 181, 355, 622
dysgenetic DSD, 650 Ectopic testicles, 529, 531, 533
EIS, 685 Ectopic ureter
embryology, 639–642 association with, 197
gonadal dysgenesis, 673–677 bilateral single-system ureteral ectopia, 197
imperforated hymen, 637 clinical features, 199–200
incidence, 637 diagnosis, 200
isolated 17,20-lyase deficiency, 685 duplicated renal collecting system, 197
Klinefelter syndrome, 683 embryology and pathophysiology, 198–199
Leydig cell hypoplasia, 685 in females, 197, 198
MGD, 638 in males, 197, 198
micropenis, 683–384 surgical treatment, 200–202
MIS, 638 Weigert-Meyer rule, 197
newborn evaluation, 651–653 Encysted hydroceles, 412
ovarian DSD, 650 Endocrine emergency situation, 635
ovotesticular DSD, 650 End stage renal disease (ESRD), 2, 7, 241, 425,
ovotestis DSD, 679–682 427, 434
PMDS, 670–672 Epididymal appendage
PPSH, 685 acute scrotal pain, 566
sex chromosome DSDs, 646–647 appendix testis, 608
sexual and gonadal differentiation, 642–645 clinical features, 567, 609
surgical corrections, 657–659 clinical investigations, 567–568, 609–610
testicular DSD, 650 diagrammatic representation, 566, 608, 609
treatment, 656–657 embryology, 567, 609
triple X syndrome, 683 epididymal appendix, 608
uterus didelphys, 684 incidence, 566, 608
46,XX disorders, 648–649 symptoms, 566
46,XY disorders, 647–648 treatment, 567–568, 609–610
Distal penile hypospadias, 458, 460 Epididymo-orchitis, 199, 554, 555, 559, 601, 610
Distal renal tubular acidosis (dRTA), 272, 274–275, Estrogen insensitivity syndrome (EIS), 685
282, 284 European Society for Pediatric Endocrinology (ESPE),
Diuretic nuclear renography, 189 645, 646
Dorsal penile nerve block (DPNB), 482 Extravaginal torsion
Down syndrome, 15, 532 clinical and intraoperative photographs, 556,
DSD. See Disorder of sex development (DSD) 557, 562
Duplex (duplicated) system clinical features, 562–565
abdominal and pelvic ultrasound, 194–195 etiology of, 562
bifid ureters, 191 treatment, 563–566
classification, 192–193 Extravesical detrusorrhaphy, 266, 267
clinical features, 193
complete ureteral duplication, 189, 191–192
complication, 192 F
CT scanning, 192 Familial hypomagnesemia with hypercalciuria and
CT urography, 195 nephrocalcinosis (FHHNC), 272, 282, 284
incomplete ureteral duplication, 189, 191 Female epispadias
IVU, 193, 194 diagnosis, 348
micturating cystourethrography, 195 incidence, 348
MR urography, 195, 196 prognosis, 349
nuclear scan, 195 surgical repair, 349
scintigraphy, 192 Female pseudohermaphrodites. See Congenital
treatment and prognosis, 195–197 adrenal hyperplasia (CAH)
unilateral or bilateral, 189, 190 Foley’s catheter, 282, 369, 472, 474, 629
692 Index
Fowler-Stephens principle, 541 encysted hydrocele, 412

Fraser syndrome, 621, 625 noncommunicating, 411–412
Frasier syndrome, 639 reactive, 412
treatment, 413
Hydronephrosis
G abdominal and pelvic ultrasound, 58, 59
Gastroschesis, 532, 535 abdominal CT-scan, 62, 63
Genotypic/chromosomal sex, 637 abdominal x-ray, 58, 59
Germ-cell tumors antegrade/retrograde pyelography, 62, 64
ITGCN, 572 antenatal hydronephrosis
mixed forms, 575 antibiotic prophylaxis, 68
precursor lesions, 574 bilateral, 67–68
pure forms, 574–575 diuretic renography, 67
seminomas, 571, 576 fetal, 65, 66
teratoma, 570–572, 576, 586–587 infants, management of, 67
yolk sac tumors, 570, 571, 575, 585–586 moderate and mild unilateral, 68
Glandular hypospadias, 458 pathological causes, 66
Glenn-Anderson repair, 266, 267 postnatal radiology, 66–67
Gomco clamp, 479, 482, 486, 488, 490, 495 risk of, 65–66
Gonadal dysgenesis, 570, 656–657 severe unilateral, 68
asymmetrical gonads, 674 severity, 66, 67
definition, 673 surgical management, 68–69
degree of virilization, 674 systematic review, 66
DMP, 676 Tc99m MAG3, 67
dysgenetic testis, 673–674 ultrasonography, 66
embryology, 674 VCUG, 67
malignancy risk, 675 vesicoureteral reflux, 65
MGD, 676 classification, 54–57
partial gonadal dysgenesis, 675 clinical features, 57–58
pathogenesis, 674 distension and dilation, 43, 44
Perrault syndrome, 676 diuretic renography, 59, 61
pure gonadal dysgenesis, 676–677 etiology
streak gonad, 673 antenatal, 54–55
treatment, 676 causes of, 52, 54
Turner syndrome, 675 MCDK, 52–54
XX gonadal dysgenesis, 676 neonates and children, 49–53
Gonadoblastomas, 381, 571, 574, 578, 579, 590, IVU, 58, 60
667, 674–676 MCU, 58, 60, 61
Granulosa cell tumour, 575 megaureter, 44, 47
MRU, 62–64
obstruction, 43–44
H pathophysiology
Hereditary hypophosphatemic rickets with hypercalciuria acute hydronephrosis, 46
(HHRH), 274, 275, 282 chronic hydronephrosis, 46–49
Hermaphroditism, 636, 645, 646, 650, 679 functional causes, 45, 48
High-flow priapism glomerular filtration rate, 46
causes, 504, 505 hypertension, 47
characteristics, 507 longstanding, 49
diagnosis, 508 obstruction, 45–46
genitourinary trauma, 507 persistent hydronephrosis, 48–49
SCD, 513–515 urinary stasis, 47, 49
treatment, 502, 511–512 prenatally diagnosis, 44
Horseshoe kidney, 12, 14–15, 18, 26, 72, 104, 112, 181, renal urography, 61–62
355, 365, 383, 418, 622 severity, 45
Human papilloma virus (HPV), 478, 485 SFU grade, 44–45
Hydrocele, 614, 615 signs and symptoms, 43
abdomino-scrotal, 413 treatment, 63, 65
canal of Nuck, 412 ureterovesical junction, 44, 45, 47
communicating, 411, 412 vesicoureteral reflux, 44, 46
embryology, 410 Hydro-ureteronephrosis, 440
Index 693
Hypercalciuria, 273–274 testosterone injection, 464

Hypoplastic testis, 531, 533 TIP procedure, 467–470, 472
Hypospadias urethroplasty, 467, 468
chordee shape, 451–453 undescended testes, 455–457
chordee without hypospadias, 454 urinary diversion, 472
classification winged prepuce, 452
coronal, 458, 459 Hypovirilization, 570
distal penile, 458, 460 Hypoxanthine-guanine phosphoribosyl transferase
glandular, 458 (HPRT) deficiency, 278, 384
midshaft, 458, 460
penoscrotal, 458, 461
perineal, 458, 462 I
proximal penile, 458, 461 Idiopathic hypercalciuria, 273, 274, 279, 283
subcoronal, 458, 459 Idiopathic scrotal edema, 554, 560, 601, 612–613
clinical features Imperforate hymen, 619–621
abnormal prepuce and normal meatus, 464 Incarcerated inguinal hernia, 403, 404, 601, 613, 614
ectopic meatus on surface of penis, 462, 463 Indirect inguinal hernia, 353, 401, 404–405
glanular groove, 462, 463 Inguinal hernias
hooded foreskin, 463 Amyand’s hernia, 406, 407
MIP, 463 Busse’s hernia, 405, 406
severe chordee, 463 clinical features, 403–404
cosmetics, 454 complications
curvature of the penis, 452, 453 hydrocele formation and recurrence, 410
definition, 451 hypesthesia, 410
DSD, 457 iatrogenic cryptorchidism, 410
ectopic urethral meatus, 452 incarceration, 406–408
effects, 455 infertility, 410
embryology, 455–456 metachronous contralateral hernia, 410
etiology, 456 scrotal hematoma, 410
hypospadiologists, 454 strangulation, 408, 409
incidence, 451 testicular atrophy, 410
lack of prepuce, 452 wound infection, 410
mild vesicoureteral reflux, 457 direct, 405
MIP, 451, 454, 456, 463, 487 etiology, 402–403
postoperative complications incidence, 401–402
deviated penis, 475 indirect, 404–405
hairy urethra, 474–475 Littre’s hernia, 405
immediate, 473 Maydl’s hernia, 406
long-term, 474 Richter’s hernia, 405
meatal stenosis, 474 sliding, 405
urethral diverticula, 474, 475 treatment, 408
urethral strictures, 474 International Classification System for VUR,
urethrocutaneous fistula, 473, 474 246–247
postoperative penis, 454 International Society of Pediatric
prostatic utricle, 457 Oncology (SIOP), 103, 107, 113, 121, 124
repair, 454–455 Intersex. See Disorder of sex development (DSD)
scrotal transposition, 453 Intratubular germ cell neoplasia (ITGCN), 572
treatment Intrauterine testicular torsion, 529, 533, 562,
Byer’s flaps, 464, 465 602, 608
glanular hypospadias, 467 Intravenous pyelography (IVP), 32, 81, 183, 268, 280
HCG, 464 Intravenous urography (IVU), 58, 60
hormonal therapy, 464, 466 duplex (duplicated) system, 193, 194
LABO technique, 468 ectopic ureter, 200
lateral based flap, 468 PUJ obstruction, 81, 83
Mathieu technique, 468 Ischemic priapism. See Low flow priapism
middle hypospadias, 467 Isolated 17,20-lyase deficiency, 685
posterior hypospadias, 468, 471
posthypospadias repair, 466, 467
psychological effect, 464, 466 J
surgical repair, 464, 465 Juvenile granulosa cell tumors, 572, 576, 587, 588
694 Index
K skin bridges, 493, 498

Kallmann’s syndrome, 35, 532 skin chordee, 493, 498
Khitan. See Male circumcision unsatisfactory cosmetic appearance, 493, 497
Kidney urethral fistula, 493, 499
abnormalities definition, 477
agenesis, 5–6 devices used, 479
crossed fused renal ectopia, 15–17 formal surgical circumcision, 478
cysts, 11–12 history
dysplasia, 8–10 Africans, 480, 481
ectopic kidney, 12, 13, 17–18 Arabian Peninsula, 480
fusion, 12, 13 Christianity, 481
horseshoe kidney, 12, 14–15 Egypt, 480
hypoplasia, 6–7 Encyclopedia Britannica, 482
multicystic kidney, 8–10 Great Britain, 481
polycystic kidney disease, 8, 10 HIV infection, 482
supernumerary kidneys, 7 Jewish and Islamic faiths, 480
Klinefelter syndrome, 538, 577, 578, 646, 650, 683 Judaism, 480
masturbation, 481
Mediterraneans, 480
L Middle Eastern, 480
Lateral Based Onlay (LABO) technique, 468 Muslim males, 480
Laurence-Moon-Biedl syndrome, 532 Oceania, 480
Lawson Wilkins Pediatric Endocrine Society (LWPES), Philippines, 481
645, 646 religious significance, 481
Leydig cell hypoplasia, 678, 685 United States, 481
Leydig cell tumor, 569, 570, 575, 587–588 indications
Lich-Gregoire repair, 266, 267 balanitis/posthitis, 483
Littre’s hernia, 405 contraindications, 485–486
Low flow priapism HPV and cervical cancer management, 485
causes, 502, 504–506, 508 medical, 483
characteristic features, 508 paraphimosis, 483
corpora cavernosa, 507 penile cancer, 485
diagnosis, 508 phimosis, 483
management, 503 STDs management, 484
pain, 508 UTIs management, 484
permanent cavernosal structural damage, 503 pain management, 482
SCD, 513, 514 pathophysiology, 479
treatment, 503, 510–511 plastibel circumcision, 478, 479
venous drainage, 507 prevalence, 477–478
surgical procedure
bone cutter, 488, 489
M circumplast, 489, 494
Magnetic resonance urography (MRU), 16, 62–64, 82, epispadias, 487
189, 192, 196, 200, 205, 257 Gomco clamp, 490, 495
MAGPI (Meatal Advancement Glanduloplasty hypospadias, 487, 488
Incorporated) procedure, 467 interventions, 486
Male circumcision megameatus, 487, 488
anatomy, 479–480 Mogen clamp, 490, 495
benefits, 478 open, 486
complications, 479 oral acetaminophen/paracetamol, 486
bleeding, 492–493, 496 plastibel circumcision, 488–494
concealed penis, 493, 497 portable bipolar diathermy, 489, 493
gangrene glans penis, 493, 499 Shang ring, 490, 496
incomplete circumcision, 493, 499 Malignant rhabdoid tumor (MRT)
infection, 493 chromosome 22, 143
meatal stenosis, 493, 496 clinical features, 145–146
pain, 492 definition, 143
psychological effects, 494 diagnosis and diagnosis, 146–149
retained plastibel, 493, 498 etiology, 144
sexual effects, 493–494 histologic findings, 144–145
Index 695
mortality/morbidity, 150 Micturating cystourethrogram (MCUG), 205, 435, 440

pathophysiology, 144 Micturition function, 296, 299
presentation, 144 Midshaft hypospadias, 458, 460, 467, 468
treatment and outcome, 149–150 Mild androgen insensitivity syndrome, 670, 683
Mathieu technique, 468 Mitrofanoff technique, 390, 391, 437, 440
Maydl’s hernia, 406 Mixed germ cell tumors, 571, 574, 575, 587
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, Mixed gonadal dysgenesis (MGD), 638, 646, 647, 651,
621–623 654, 674, 676
MCDK. See Multi cystic dysplastic kidney (MCDK) Mogen clamp, 479, 482, 486, 488, 490, 495
McKusick-Kaufman syndrome, 623, 625 Moorman’s ring. See Cobb’s collar
Median umbilical ligament, 2, 4, 393 Müllerian duct cyst, 445, 448–449
Megacystis-microcolon-intestinal hypoperistalsis Mullerian inhibiting substance (MIS) deficiency, 638
syndrome (MMIH syndrome) Multi cystic dysplastic kidney (MCDK), 8, 9, 52–54
associated anomalies, 376–378 associated anomalies, 180–181
clinical features, 376 bilateral, 173, 174
definition, 373 classification, 179
dilated stomach, 374, 376–378 clinical features, 182
dilated urinary balder, 374, 376–378 complication, 174
etiology, 374–376 embryology, 174–175
hydronephrosis, 373, 374, 376 etiology and pathophysiology, 175
lower contrast enema, 375 histologic findings, 175–178
prenatal diagnosis, 373, 376 investigations, 182–184
prognosis, 377 natural history of, 178–179
treatment noncommunicating cysts, 173, 174
ileostomy, 377, 379 treatment, 183–185
multi-organ transplantation, 377, 378 unilateral, 173, 174
multivisceral transplantation, 378 Multilocular cystic renal tumor (MCRT)
vesicostomy, 377 abdominal ultrasound and CT-scan findings, 167
Megameatus with intact prepuce (MIP), 451, 454, calcification, 168
456, 463, 487 CPDN, 165, 166
Mega ureter, 21, 22, 187, 212–215 cystic nephroma, 165–167
Mesoblastic nephroma differential diagnosis, 166
CBC, 137 gross features, 167
classification, 133–134 microscopic features, 167
clinical features, 136–137 modification, 165
CT-scan, 137, 138 treatment, 168
definition, 132 Mummy wrapping, 357
differential diagnosis, 132
epidemiology, 134
histopathology, 134–136 N
live function tests, 137 NBSD. See Neurogenic bladder sphincter dysfunction
MRI, 137–138 (NBSD)
paraneoplastic syndromes, 132 Neurogenic bladder sphincter dysfunction (NBSD)
plain radiograph, 137 acquired causes, 295
prognosis, 138 anticholinergics
serum electrolyte, BUN and Fesoterodine, 318
creatinine, 137 oxybutynin, 317–318
treatment, 138 Tolterodine L-tartrate, 318
ultrasound, 137 Trospium, 318
Mesonephros, 2, 3, 174, 198, 596 Botulinum A toxin injections, 318
Metanephric adenoma (MA) classification of, 313, 314
clinical features, 164–165 clean intermittent catheterization, 316–317
diagnosis, 164 congenital neural tube defects, 295
histologic analysis, 163–164 conservative management of, 295
histopathology, 164 detrusor muscle, 295
treatment, 165 etiology and clinical features
Metanephros, 2–4, 17, 174 advantages, 306
Micropenis, 34–36, 485, 538, 625, 652, 654, 668, anticholinergic drugs, 305
683–685 causes, 304
Micturating cystourethrogram (MCU), 58–61 cerebral palsy, 307–309
696 Index
Neurogenic bladder sphincter dysfunction (NBSD) (cont.) Pelviureteric junction (PUJ) obstruction
clean intermittent catheterization, 305 abdominal CT-scan, 82, 89
detrusor areflexia, 303 abdominal MRI, 82, 85
detrusor hyperreflexia, 302 abdominal radiograph, 81
detrusor instability, 303 abdominal ultrasound, 81, 82
DHIC, 303 clinical features, 76–80
DSD, 302 definition, 71
DSD-DH, 302–303 diagnosis, 71
myelomeningocele, 304, 305 diagrammatic representation, 71, 72
neurogenic dysfunction, 304 diuretic renography, 82, 83, 85, 86
occult spinal dysraphism, 306–307 embryology, 73
outflow obstruction, 303 etiology
overactive bladder, 303 primary causes, 74, 75
peripheral neuropathy, 304 secondary causes, 74–77
sacral agenesis, 307, 308 follow-up, 97–98
sacral cord injury, 304 incidence, 71
surgical procedures, 306 intermittent UPJ obstruction, 81
traumatic injuries, spine, 309 intravenous urography, 81, 83
urinary retention, 303 intrinsic, causes of, 71–72
investigations and diagnosis, 310–313 newborns, management of, 88–89
management, 314–316 pathophysiology, 73–74
medical management, 296 post-operative complications, 97–98
pathophysiological changes of, 301–302 prenatal evaluation, 79–80
risk factors, 296 pressure flow studies, 87–88
surgical management, 320–321 retrograde/antegrade pyelography, 86–87
tricyclic antidepressant drugs, 318–320 serum electrolytes, BUN and creatinine, 81
urinary bladder (see Urinary bladder) treatment
urinary sphincter, 295 asymptomatic patients, 90–92
urodynamic assessment, 295, 296 balloon dilatations, 95–97
Neuronal nicotinic acetylcholine receptor (ηAChR), 375 endopyeloplasty:, 95
Noncommunicating hydroceles, 411–412 endoscopic treatment, 94–95
Nonischemic priapism. See High-flow priapism laparoscopic pyeloplasty, 93–94
Non-refluxing/non-obstructed megureter, 217, 222 open surgical therapy, 91–93
Noonan syndrome, 532 patients selection, 89
ureterocalicostomy, 95
urine analysis and culture, 81
O urological anomalies, 72
Obstructed megaureter, 217, 218, 221–222, 231 VCUG, 86
Occult spinal dysraphism, 306–307 Penis at 12, 638
OEIS complex. See Cloacal exstrophy Penoscrotal hypospadias, 38, 446, 458, 461, 647
Oligomeganephronia, 6–7, 18 Perineal hypospadias, 38, 446, 458, 462, 532
Omphaloceles, 365, 532, 535 Perrault syndrome, 673, 676
Open antireflux surgery, 265, 266, 268 Persistent Müllerian duct syndrome (PMDS), 670–672
Orchidopexy, 527, 529, 538, 539, 541 AMH, 287
Orchitis, 610 classification, 291
Ovotestis DSD, 679–682 clinical features of, 287, 291–292
embryology of, 287–290
etiology and inheritance, 290–291
P prognosis, 293
PAIS. See Partial androgen insensitivity treatment, 292–293
syndrome (PAIS) Phenotypic sex, 636, 638, 642, 645, 650, 674
Pampiniform venous plexus, 545 Phosphoribosyl pyrophosphate synthetase superactivity
Partial androgen insensitivity syndrome (PAIS) (PRPSS), 277–278, 284
clinical photographs, 669 Plastibel circumcision, 478, 479, 482, 486, 488–494, 498
diagnosis, 669, 670 Politano-Leadbetter procedure, 266–267
symptoms, 638, 668 Polycystic kidney disease (PCKD), 8, 10, 179, 182–183
treatment, 670 Pontine micturition center (PMC), 297–298, 301
Partial androgen resistance, 656 Posterior sagittal anorectovaginourethroplasty
Partial gonadal dysgenesis, 647, 648, 651, 655, 673, 675 (PSARVUP), 382, 383, 387, 388
Patent urachuss, 395–397 Posterior urethral valve (PUV)
Index 697
classification, 426 PUV, 440

type I, 427 renal transplantation, 441
type II, 427 vesico-ureteric reflux, 440
type III, 427 Postpubertal orchiopexy, 570
definition, 423 Potter classification of renal
delayed presentation, 427 dysplasia, 179
embryology, 424–425 Prader–Willi syndrome, 35, 532
ESRD, 425, 427, 434 Priapism
fertility, 441 acute priapism, 508
follow-ups, 438–439 causes, 505
hydro-ureteronephrosis, 440 in childhood and adolescence, 501
incidence, 423, 427 clinical features, 508–509
investigations and diagnosis clinical investigations, 509–510
antenatal ultrasound, 428, 430–431 complications, 524
chest radiographs, 428 definition, 501
computed tomography, 432 early intervention, 501, 503
cystourethroscopy, 433 erectile dysfunction, 501
IVU, 431–432 etiology, 505–507
MRI, 432 high flow priapism (see High flow priapism)
nuclear imaging, 432–433 low flow priapism (see Low flow priapism)
plain abdominal radiographs, 428 medications, 505
renal and bladder ultrasonography, 428, 429 nocturnal episodes, 501
serum electrolytes, 428 pathophysiology, 503–505
urethral valves, 429 prognosis, 512, 524
urodynamic studies, 433 SCD (see Sickle cell disease (SCD))
VCUG, 429–433 stuttering priapism, 508
long-term outcomes, 439–440 treatment, 510–512
management Primary hyperoxaluria (PH), 275, 279, 285
aims, 433–434 Primary megaureter
augmentation cystoplasty, 437 non-refluxing unobstructed, 225, 232
bladder, 435 obstructed, 221, 232
continent appendicovesicostomy, 437 refluxing, 232
cutaneous ureterostomies, 436 symptoms, 218
cystoscopy, 435 unobstructed, 221
endoscopic treatments, 434 Pronephros, 3, 174, 198
multidisciplinary team, 433 Prostatic utricular cyst
neonatal, 434–435 classification, 445–446
postnatal primary valve ablation, 436 clinical features, 446
prenatal intervention, 434 CT-scan, 447, 448
primary valve resection, 435 definition, 443
refluxing ureterostomy, 437 embryology, 445
renal dysfunction, 434 function, 443
surgical treatment, 436 hypospadias, 444
urinary diversion, 434 investigations, 446–447
vesicostomy, 436 location, 443
medications, 437–438 MRI, 448
pathophysiology müllerian duct cyst, 448–449
bladder dysfunction, 426 Prune belly syndrome, 444
bladder emptying, 425 surgical treatment, 447–449
congenital obstruction, urinary VCUG, 446–447
tract, 425 Proximal penile hypospadias, 458, 461
hydronephrosis, 426 Prune belly syndrome, 30, 56, 224, 397, 444, 532,
protective mechanisms, 426 533, 538
renal deterioration, 425 PSARVUP. See Posterior sagittal
renal maldevelopment, 425 anorectovaginourethroplasty (PSARVUP)
vesicoureteral reflux, 426 Pseudovaginal perineoscrotal
physical findings, 428 hypospadias (PPSH), 685
prenatal diagnosis, 427 Pure gonadal dysgenesis, 578, 590, 650, 651, 653,
prognosis, 438–439 673, 676–677
pulmonary hypoplasia, 428 PUV. See Posterior urethral valve (PUV)
698 Index
R classification, 133–134
Radionuclide scan, 183, 555, 606 clinical features, 136–137
Reactive hydroceles, 412 CT-scan, 137, 138
Refluxing megaureter, 217, 222, 224 definition, 132
Refluxing/obstructed megaureter, 217 differential diagnosis, 132
Renal cell carcinoma (RCC) epidemiology, 134
classification, 153 histopathology, 134–136
clinical features, 154–155 live function tests, 137
diagnosis, 155 MRI, 137–138
histological evidence, 150 paraneoplastic syndromes, 132
histopathology, 151–152 plain radiograph, 137
incidence, 151 prognosis, 138
management, 155–156 serum electrolyte, BUN and creatinine, 137
prognosis, 156 treatment, 138
staging, 153–154 ultrasound, 137
Renal coloboma syndrome (RCS), 175, 180–181 metanephric adenoma, 163–165
Renal lymphoma clinical features, 164–165
clinical features, 161–162 diagnosis, 164
definition, 159 histologic analysis, 163–164
diagnosis, 160–161 histopathology, 164
etiology, 159–160 treatment, 165
pathogenesis, 159–160 MRT
treatment and prognosis, 162 chromosome 22, 143
Renal transplantation, 424, 425, 434, 441 clinical features, 145–146
Renal tumors definition, 143
age at presentation, 102 diagnosis and diagnosis, 146–149
angiomyolipoma etiology, 144
classification, 157–158 histologic findings, 144–145
clinical features, 158 mortality/morbidity, 150
diagnosis, 158–159 pathophysiology, 144
histopathology, 157 presentation, 144
incidence, 156–157 treatment and outcome, 149–150
treatment and prognosis, 159 ossifying, 162–163
CCSK RCC
clinical features, 140 classification, 153
definition, 138 clinical features, 154–155
diagnosis, 140 diagnosis, 155
histopathology, 140–141 histological evidence, 150
pathophysiology, 139–140 histopathology, 151–152
prognosis, 142 incidence, 151
treatment, 141–142 management, 155–156
lymphoma prognosis, 156
clinical features, 161–162 staging, 153–154
definition, 159 Wilms’ tumor (see Wilms’ tumor)
diagnosis, 160–161 Retractile testicles, 529, 531, 533, 534
etiology, 159–160 Retrograde pyelography, 62, 81, 86, 183
pathogenesis, 159–160 Retroperitoneal lymph node dissection (RPLND), 573,
treatment and prognosis, 162 591, 592
MCRT Richter’s hernia, 405
abdominal ultrasound and CT-scan findings, 167
calcification, 168
CPDN, 165, 166 S
cystic nephroma, 165–167 SCD. See Sickle cell disease (SCD)
differential diagnosis, 166 Schönlein-Henoch purpura, 601, 613, 614
gross features, 167 Secondary hyperoxaluria, 276, 284
microscopic features, 167 Secondary megaureter
modification, 165 causes of, 218–223, 226
treatment, 168 nonrefluxing/nonobstructed megaureter, 222–223
mesoblastic nephroma obstructed megaureter, 221
CBC, 137 refluxing megaureter, 222
Index 699
Seminomas, 542, 543, 570–572, 574, 576, 579, Testicular torsion

582, 585, 665, 675, 676, 681 acute scrotal pain, 553, 554
Sertoli cell tumors, 571–575, 588–589 bell-clapper deformity, 553, 554
Sex cord/Gonadal stromal tumors bilateral testicular torsion, 553
adrenal rests, 588 causes, 553, 602
granulosa cell tumour, 575 clinical features, 558–560
incompletely differentiated, 575 clinical investigations, 606, 607
juvenile granulosa cell tumors, 576, 588 degree of torsion, 553, 557–558, 605–606
Leydig cell tumor, 569, 570, 575, 587–588 diagnosis, 554–556
mixed types, 575, 589 duration of torsion, 558
sertoli cell tumors, 575, 588–589 etiology, 554–555
Thecoma Fibroma Group, 575 extravaginal torsion (see Extravaginal torsion)
Sexually transmitted diseases (STDs), 484 clinical features, 605
Shang ring, 488, 491, 496 diagrammatic representation, 602
Sickle cell anemia, 504–505, 517 etiology, 603–604
Sickle cell disease (SCD) in neonates, 603
acute severe priapism, 515 incidence, 554
clinical features, 517–518 intermittent testicular torsion, 556
clinical photographs, 501, 502, 513 intrauterine testicular torsion, 602
complication, 501, 503 intravaginal torsion, 556, 558
epidemiology, 514 in adolescents, 602
high-flow priapism, 513–515 clinical features, 604–605
low flow priapism, 513, 514 diagrammatic representation, 602
mean age, 501 etiology, 603, 604
pathophysiology, 515–517 incidence, 602
prepubertal period, 501 risk factors, 554–555
stuttering priapism, 501, 515, 521–524 treatment, 560–562, 606–608
treatment, 519–522 Testicular tumors
Sliding inguinal hernia, 405 adjuvant therapy, 573
Snodgrass urethroplasty. See Tubularized incised plate alpha-fetoprotein (AFP), 573
(TIP) repair benign, 574
Society for Fetal Urology (SFU) grade, 44–45, 78–79 bimodal age distribution, 569
Spigelian hernia, 532, 534 carcinoid, 575
Splenogonadal fusion Children’s Oncology Group staging system, 580, 581
causes, 613–614 clinical features, 579–580
clinical features, 596–598 clinical investigations, 582–583
clinical intraoperative photograph, 595, 596, 616 collecting ducts and rete tumors, 575
clinical investigations, 598 cystic dysplasia, 590
continuous splenogonadal fusion, 595–597, 616 distant metastatic staging, 581
definition, 595 epidermoid cysts, 589
diagnosis, 595, 596, 616 etiology of, 576–579
discontinuous splenogonadal fusion, 595–597, 616 germ-cell tumors
etiology, 596 ITGCN, 572
intra-operative frozen section biopsy, 595 mixed forms, 575
male-to-female ratio, 615 precursor lesions, 574
malformations, 597 pure forms, 574–575
SGFLD, 597 seminomas, 571, 576
symptoms, 595 teratoma, 570–572, 576, 586–587
treatment, 596, 598–599, 616 yolk sac tumors, 570, 571, 575, 585–586
Splenogonadal fusion limb defect syndrome (SGFLD), gonadal dysgenesis, 570
597 gonadoblastomas, 571, 574, 590
Steroidogenic factor 1 (SF-1), 639 haematopoietic tumors, 575
Subcoronal hypospadias, 455, 458, 459 hypovirilization, 570
Suprapubic urinary diversion (cistofix), 472 incidence of, 569
inguinal orchiectomy, 572
intergroup staging system, 581
T intratubular germ cell neoplasia, 570
Teratoma, 570–572, 576, 586–587 leukemia and lymphoma, 590–591
Testicular feminization syndrome, 528, 578, 665–670 malignant, 574
Testicular microlithiasis (TM), 577, 589–590 mesenchymal tumors, 575
700 Index
Testicular tumors (cont.) embryology, 530

mixed germ cell tumors, 571, 574, 575, 587 epididymal abnormality, 536, 537
ovarian epithelial types tumors, 575 gastroschesis, 532, 535
paratesticular rhabdomyosarcoma, 591–592 histopathology, 532–533
paratesticular structure tumors, 575 hypoplastic testis, 531, 533
pediatric prepubertal testicular tumors, 571 incidence of, 527
postpubertal orchiopexy, 570 infertility, 541–542
prevalence of, 569 inguinal hernia, 529
primary testicular tumors, 574 Kallmann’s syndrome, 532
primary tumor staging, 581 Laurence-Moon-Biedl syndrome, 532
prognosis and outcomes, 592 Noonan syndrome, 532
regional lymph node staging, 581–582 normal testicular development, 530
retroperitoneal lymph node dissection, 573 omphaloceles, 532, 535
secondary testicular tumors, 574, 575 penoscrotal/perineal hypospadias, 532
serum tumor marker staging, 581 Prader–Willi syndrome, 532
sex cord/Gonadal stromal tumors prevalence, 527, 528
adrenal rests, 588 prune belly syndrome, 532, 533
granulosa cell tumour, 575 retractile testicles, 529, 531, 534
incompletely differentiated, 575 spermatogenesis, 531
juvenile granulosa cell tumors, 576, 588 spigelian hernia, 532, 534
Leydig cell tumor, 569, 570, 575, symptoms, 529
587–588 testicular descent, 530–531
mixed types, 575, 589 testicular feminization
sertoli cell tumors, 575, 588–589 syndrome, 528
Thecoma Fibroma Group, 575 treatment
simple testicular cyst, 589 hormonal treatment, 538–539
symptoms, 571 length-increasing maneuvers, 541
testis-sparing approach, 572, 573 orchidopexy, 527, 529, 538, 541
TM, 589–590 surgical treatment, 539–541
TNM staging system, 580–581 true undescended testicles, 529, 533
transscrotal biopsy, 572 vanished testis, 531, 533–534
treatment, 583–585 Urachal cyst, 28, 30, 393, 395, 397–399
Torsion of testicular appendices. See Epididymal Urachal remnants
appendage classification
Transurethral urinary diversion (Foley’s catheter), 472 inflammation, 396
Triple X syndrome, 683 patent urachuss, 395, 396
True undescended testicles, 528, 529, 533 urachal cyst, 395
Tubularized incised plate (TIP) repair, 454, urachal-umbilical sinus, 395, 396
467–469, 471, 472 vesicourachal diverticulum, 395, 396
Tuli. See Male circumcision clinical features
asymptomatic patients, 396
patent urachus, 396, 397
U umbilical-urachal sinus, 397
Undescended testes urachal cyst, 397–399
American Urological Association vesicourachal diverticulum, 397
guidelines, 528–529 clinical problems, 393
ascent testis, 531, 534 embryology, 393–395
bilateral nonpalpable testes, 529–530 management, 399–400
birth defect, 527 median umbilical ligament, 393
cancer risk, 542–543 retzius, 393
causes, 528, 531–532 tumors, 398–399
clinical features and diagnosis, 537–538 Urachal-umbilical sinus, 395, 396
clinical photograph, 527 Ureter
cloacal exstrophy, 532, 535 abnormalities
complications, 529 duplication of, 18–20
congenital adrenal hyperplasia, 529 ectopic ureteral orifice, 20
definition, 527 mega-ureter, obstruction, 21–22, 25, 26
down syndrome, 532 ureteral atresia, 18, 19
dysgenetic testis, 531, 533 ureterocele, 19, 21
ectopic testicles, 529, 531, 533 ureteropelvic junction, 20–23
Index 701
Ureterocele FHHNC, 274

classification, 203 gastrostomy tube-fed, 273
clinical features, 204 genitourinary anomalies, 273
congenital saccular dilatation, 202 HHRH, 275
ectopic ureterocele, 203 idiopathic, 273
incidence of, 203 hyperoxaluria
investigations and diagnosis, 204–206 primary hyperoxaluria, 275
surgical interventions, 203 secondary hyperoxaluria, 276
treatment, 205–208 hyperuricosuria, 277–278
bladder neck reconstruction, 207 hypocitraturia, 276
conservative treatment, 206, 208 investigations
single system ureterocele, 208 abdominal CT-scan, 280
surgical interventions, 208 metabolic, 281–282
upper pole hemi-nephrectomy, 205–207 radiopaque stones, 280, 281
ureterocele puncture, 205, 207 ultrasonography, 280
uretero-ureterostomy, 207–208 management of, 282–285
Urinary bladder renal transplant complication, 272
micturition function, 301 risk factors for, 272, 273
central and peripheral nervous systems, 296 urinary calcium increases, 272
parasympathetic nervous system, 298, 300 urinary stones developments, 272
PMC, 297, 298 Uterus didelphys, 6, 684
pudendal nerve, 296 UTI. See Urinary tract infection (UTI)
somatic nerve, 299, 300 Utricular cyst. See Prostatic utricular cyst
spinal reflux, 297
sympathetic nervous system, 298, 300
unobstructed urinary flow and bladder emptying, V
296 VACTERL association, 15, 16, 181, 423
storage function Vaginal atresia
central and peripheral nervous systems, 296 associated anomalies, 622
control of, 299 Bardet-Biedl syndrome, 621
low-pressure reservoir, 296 classification, 621–622
Urinary diversion, 196, 303, 319–321, 339, 348, 349, clinical features, 623–625
351, 357, 359, 368, 371, 372, 390, 391, 434, congenital developmental defect, 621
437, 440, 441, 472 embryology, 622–623
Urinary tract infection (UTI) Fraser syndrome, 621
antibiotics investigations, 625–628
oral treatment, 330–332 MRKH, 621
parenteral treatment, 332, 333 surgical management, 628–633
prophylaxis, 333, 334 syndromes, 621
clinical features, 325–327 Valves unilateral reflux dysplasia (VURD)
diagnosis of, 324 syndrome, 424, 439
etiology, 324–325 Vanished testis, 531, 533–534
incidence of, 323–324 Varicocele, 614, 615
investigations and diagnosis, 327–330 causes, 545
pathophysiology, 325 clinical features, 548
urological abnormalities, 324 diagnosis, 548–549
Urolithiasis diagrammatic representation, 545
chemical composition, 273 embolization therapy, 549
classification of, 278 etiology, 546
clinical features, 278–280 grading, 547–548
complications of, 282 incidence, 545, 546
cystinuria, 276–277, 284 medical treatment, 549
drugs, 272 pathophysiology, 546–547
fluid intake, 272 postoperative complications, 550
hypercalciuria prognosis, 551
Bartter syndrome, 274 situs inversus, 546
causes of, 274 surgical treatment, 550
definition, 273 treatment indications, 549
dent disease, 274 unilateral right-side varicocele, 546
dRTA, 274–275 Varicocelectomy, 550, 551
702 Index
Ventriculoperitoneal shunt, 403, 408, 409 Wilms’ tumor

Vesicourachal diverticulum, 395, 397 abdominal ultrasound, 115, 117
Vesicoureteral reflux (VUR) anaplasia, 103
antibiotics, prophylaxis, 261 cases of, 102–103
anticholinergics, 261–262 chemotherapy, 104
atrophic kidneys secondary, 238, 239 chest CT-scan, 118, 120–122
clinical features, 250–252, 254 chest radiograph, 115, 116
congenital megaureter, 218, 234 chromosome 11, 104
congenital ureteral anomalies, 208–212 clinical features, 110–112
diagnosis of, 238 clinical photograph, 102
etiology of, 247–249, 251–253 congenital anomalies, 104
incidence of, 238 elements, 103
investigations etiology, 104–105
abdominal and pelvic CT-scan and extrarenal, 131
MRU, 257, 258 favorable, 103
abdominal ultrasound, 255 histopathology, 105–108
DMSA renal scan:, 256 intravenous urography, 118, 119
non-contaminated urine specimen, 254 MRI scanning, 118–120
radionuclide cystography, 256 multimodality therapy, 103
urodynamic studies, 256–257 nephroblastomatosis, 108–110
VCUG, 254–256 plain abdominal radiograph, 114–115
medical treatment of, 259–260 prognosis
micturating cystourethrogram, 237, 239, 240 and complications, 121–123
mortality/morbidity, 268–269 and outcome, 130–131
pathophysiology, 240–243 rhabdomyoid differentiation, 103
prevalence of, 237, 238 risk factors, 112–113
primary, 238, 243–244 staging, 113–114
renal lesions, 239, 240 surgical complications, 130
secondary, 238–239, 245, 246 surgical considerations
surgical therapy of aspiration cytology, 124
endoscopic injection, 263–266 Bilateral Wilms’ tumor, 124, 126, 127
indications, surgical interventions, 262–263 desmopressin, 127
surgical management, 266–268 in European, 124
surveillance, 262 hypothesis, 127
Vessico-intestinal fissure. See Cloacal exstrophy inoperable tumors, 124, 125
Voiding cystourethrogram (VCUG) intracaval tumor extension, 124
congenital ureteral anomalies, 189 lung metastasis, 127, 128
ectopic ureter, 200 in North America, 123–124
UTI, 329–330 NWTSG, 124–125
Voiding cystourethrography (VCUG), 67 radiotherapy, 123
congenital megaureter, 228–230 stage I-IV anaplasia, 127
MCDK, 183 surgical management, 128–130
PUJ obstruction, 86 thoracic CT-scan, 115, 117, 118
VUR, 244, 246–249, 254, 255 Wilms tumor (WT-1) gene, 639
VUR. See Vesicoureteral reflux (VUR)
X
W 45 X/ 46 XY mixed gonadal digenesis, 657
Waardenburg syndrome type 1, 181
Weigert-Meyer rule, 188, 197
Whitaker test, 88, 189, 230, 231 Y
Williams’ syndrome, 181 Yolk sac tumors, 293, 570–576, 579, 581–587

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Ahmed H.

ISBN 978-3-319-44181-8 ISBN 978-3-319-44182-5 (eBook)

Library of Congress Control Number: 2016957149

© Springer International Publishing Switzerland 2017

Printed on acid-free paper

Springer Cham Heidelberg New York Dordrecht London

The field of pediatric urology is rapidly growing and currently it is considered

Qatif, Saudi Arabia Ahmed H. Al-Salem

I would like to express special thanks of gratitude to my family who sup-

1 Congenital Urological Malformations . . . . . . . . . . . . . . . . . . . . . 1

3.7 Management of Newborns with PUJ Obstruction . . . . . . . . . 88

4.6.3 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

6.4.3 Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193

9 Pediatric Urolithiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271

13.3.4 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345

16.4 Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396

20.4 Clinical Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446

24 Undescended Testes (Cryptorchidism) . . . . . . . . . . . . . . . . . . . . 527

27 Testicular Tumors in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . 569

29.4 Epididymitis, Orchitis, and Epididymo-orchitis . . . . . . . . . 610

1.1 Introduction • They are responsible for 34–59 % of chronic

© Springer International Publishing Switzerland 2017 1

• Nonsyndromic CAKUT: form the urogenital sinus and anal canal,

an empty renal fossa, followed by renography

1.3.6 Simple (Solitary) Renal Cyst • Calcifications may be present; these

• Horseshoe kidneys are susceptible to trauma – Ureteral duplication is reported to occur in

• The lumbar or iliac ectopic kidney is fixed

• Ectopic ureteral orifice: • Obstruction of the ureteropelvic junction

Fig. 1.28 Pelvic

Fig. 1.29 Intraoperative

APPARENT VESSEL URETER

– Cloacal exstrophy is a severe birth defect • It is thought that it results from an

– A bladder diverticulum is an outpouching – Anterior urethral valves

– Congenital bladder diverticula: infection and urinary retention are the

– Diverticular size can vary greatly, with

Fig. 1.62 A micturating cystourethrogram showing pos-

1.6 Abnormalities of the Penis

– It is extremely rare with an estimated inci- – This is an extremely rare congenital

Figs. 1.72 and 1.73 Clinical photographs showing megalopenis

– It is important to distinguish miscropenis – The effect depends on the severity of the

– Hypospadias is classified based on the site as those observed in bladder exstrophy

– It is associated with secondary spasm of

8. Gubler MC. Renal tubular dysgenesis. Pediatr

2.1 Introduction – Urinary incontinence

© Springer International Publishing Switzerland 2017 43

– This would eventually lead to: – In 15 %, the hydronephrosis persists (non-

– Grades II resolves in approximately 36 % • This interruption can occur anywhere along

– Long-standing hydronephrosis may be – Infection

urinary tract obstruction or obstruction of

• This will lead to compression of the • Renal scarring

• The causes of hydronephrosis with or without – Retroperitoneal fibrosis

• If they develop unmanageable high – Primary megaureter

– Physiologic (15 %) 2.4 Classiﬁcation

• The probability of detecting these abnormali- • Grading of antenatal hydronephrosis based on

obstructive uropathy distal to the uretero-

Fig. 2.45 Abdominal and pelvic ultrasound showing a

Fig. 2.47 Abdominal ultrasound showing an enlarged

• Diuretic renography (Fig. 2.53):

Fig. 2.52 A micturating

Fig. 2.53 A diuretic renogram of a child with left PUJ obstruction

2.7 Treatment • The presence of infection should be treated

– The severity of hydronephrosis • Ultrasonography should be performed early,

there is bilateral involvement or an affected • It is usually ordered after a VCUG has