Proceedings 2007

Index
1. Dr BS Rana Memorial Oration: Computer assisted Robotic Urologic Surgery
2. Intercostal drainage tube management guidelines
3. Chest trauma: Rib fractures and flail chest
4. Splenic Injuries
5. Management of Liver trauma
6. Tissue biopsy: A surgeon‘s viewpoint
7. Tissue biopsy: techniques and interpretation
8. Surgeon‘s viewpoint: Fluid, electrolytes and blood management
9. Investigations for thyroid disorders
10. Nodular goitre
11. Management of well differentiated thyroid cancers
12. Thyrotoxicosis
13. Current management of the complications of portal hypertension: variceal bleeding

and ascites
14. Is there still a role for surgery in bleeding portal hypertension?
15. Surgery for bleeding varices
16. Role of H.pylori in acid peptic disease
17. Update on GERD diagnosis and management
18. Peptic ulcer disease today
19. Role of surgeon in Acid-Peptic disease
20. Surgery in Acute pancreatitis
21. Treatment options for chronic pancreatitis
22. Choice of surgical procedures for chronic pancreatitis
23. Periampullary carcinoma: surgical management
24. Laparoscopic management of pancreatic diseases
1
25. Oncogenes and breast cancer
26. Investigations in a patient with early breast cancer
27. Surgical options in early breast cancer
28. Other treatment modalities in early breast cancer
29. Surgery for the early and advanced cases of hypernephroma
30. Other treatment modalities for hypernephroma
31. Management of nephroblastoma
32. Management of cystic lesions of the kidney
33. Surgeons‘ viewpoint: disaster management
34. Genitourinary tuberculosis
35. About HIV
36. Transmission of HIV
37. Prevention of HIV
38. Anti-retroviral therapy for HIV infection
39. Counseling and voluntary testing for HIV / AIDS
40. Investigations for upper limb ischaemia
41. Thoracic outlet syndrome
42. Management of chronic upper limb ischaemia
43. Management of acute upper limb ischaemia
44. Scientific basis of clinical features of intestinal obstruction
45. Congenital ano-rectal anomalies
46. Ileocaecal tuberculosis
47. Surgical complications of amoebiasis
48. Perianal fistulae
49. Pre-operative bowel preparation
50. Pre-malignant conditions of the colon and rectum
51. Management of anal cancers
52. Sphincter saving surgery for rectal cancer
53. Adjuvant therapy for rectal cancers
54. Management of recurrent rectal cancer
55. Surgical management of ulcerative colitis
56. Scientific basis of clinical features of anorectal diseases
2
CONTRIBUTORS
Intercostal drainage tube management Management of hyperthyroidism

guidelines Dr. M.Chandrasekaran
Dr. Ajit Sinha Head of Endocrine Surgery,
Senior Specialist Surgeon Madras Medical College,
& Associate Professor, Chennai
VMMC & Safdarjung Hospital, New Delhi
Investigations for portal hypertension
Rib fractures & flail chest Dr. Deepak Lahoti
Dr. S.Bal Consultant Gastroenertologist
Chief Thoracic Surgeon, New Delhi
Fortis Flt Lt Rajan Dhall Hospital,
New Delhi Non surgical management of a portal
hypertension
Management of splenic injury Dr. S.K.Jain
Dr. Arun Gupta Consultant Gastroenterolgy,
Professor of Surgery, Sita Ram Bhartia Institute, New Delhi
University College of Medical Sciences,
New Delhi Emergency management of variceal bleeding
Dr. A.K.Agarwal
Management of liver injury Professor & Head of GI Surgery,
Dr. Sham L.Singla GB Pant Hospital, New Delhi
Senior Professor of Surgery,
PGIMS, Rohtak Surgery for portal hypertension
Dr. P.Khanduri
Robotic surgery in urology – our experience Head, Department of Surgery,
Dr. N.P.Gupta St. Stephens Hospital, New Delhi
Professor & Head, Department of Urology,
All India Institute of Medical Sciences, Surgeons‟ Viewpoint: Surgical nutrition &
New Delhi Performance scores
Dr. V.K.Malik
The changing face of surgical oncology Senior Consultant of Surgery,
Dr. Donald Weaver Sir Ganga Ram Hospital, New Delhi
Chairman, Wayne University,
Detroit, USA Scientific basis of clinical features of salivary
gland tumors
Surgeon‟s Viewpoint: Tissue Biopsy- Dr. A.K.Kakar
Technique & Interpretation Director Professor and Head of Department,
Dr. A.K.Mandal Department of Surgery,
Professor and Head of Pathology, Maulana Azad Medical College, New Delhi
Maulana Azad Medical College,
New Delhi Role of H.pylori in acid peptic disease
Dr. Manoj Andley
Investigations for thyroid disorders Associate Professor of Surgery,
Dr. Ravi Kashyap Lady Hardinge Medical College, New Delhi
Joint Director & Head,
Division of Nuclear Medicine Gastro esophageal reflux disease
& Medical Informatics, Dr. A.S.Puri
INMAS, New Delhi Professor of Gastroenterology,
GB Pant Hospital, New Delhi
Management of nodular goiters
Dr. Amit Agarwal Changes in treatment strategies for acid peptic
Associate Professor, disease
Department of Endocrine Surgery, Dr. Nirmal Kumar
SGPGIMS, Lucknow Senior Consultant Gastroenterologist,
Balaji Action Medical institute,
Management of well differentiated thyroid New Delhi.
cancers
Dr. S.K.Mishra Role of surgeon in acid peptic disease
Professor & Head, Dr. T.K.Thusoo
Department of Endocrine Surgery, Head of Department of Surgery,
SGPGIMS, Lucknow Max Hospitals, New Delhi
3
Surgery in acute pancreatitis Other treatment modalities for hypernephroma
Dr. P.K.Mishra Dr. Kim Mammen
Associate Professor of GI Surgery, Professor & Head, Department of Urology,
GB Pant Hospital, New Delhi Christian Medical College, Ludhiana
Surgery for chronic pancreatitis Management of nephroblastoma

Dr. R.Tambudorai Dr. M.S.Agrawal
Reader, Department of Surgical Specialities, Professor and Consultant Urologist,
Christian Medical College, Ludhiana Urology Division, Department of Surgery,
S.N. Medical College, Agra
Surgery for pancreatic malignancy
Dr. A. Choudhary Management of cystic lesions of the kidney
Senior Consultant , Gastrintestinal Surgery, Dr. Sanjay Gupta
Sir Ganga Ram Hospital, New Delhi Professor of Surgery,
University College of Medical Sciences, Delhi
Minimal access surgery for pancreatic
disorders Surgeons‟ Viewpoint: Disaster management
Dr. Arun Prasad Dr. G.J.Singh
Senior Consultant Laparoscopic Surgeon, Head, Department of Surgery,
IP Apollo Hospital, New Delhi Deen Dayal Upadhyaya Hospital, New Delhi
Surgeons‟ Viewpoint: Fluid, electrolyte & blood Scientific basis of clinical features of inguino-
management scrotal swellings
Dr. Rakesh Kumar Dr. N.S.Hadke
Professor of Anaesthesia, Professor of Surgery,
Maulana Azad Medical College, New Delhi Maulana Azad Medical College, New Delhi
Scientific basis of clinical features of Bladder & About HIV

prostate diseases Dr. Pawan Lal
Dr. R.C.M.Kaza Assistant Professor of Surgery,
Professor of Surgery, Maulana Azad Medical College, New Delhi
Maulana Azad Medical College, New Delhi
Transmission of HIV
Oncogenes and breast cancer Dr. S.Salhan
Dr. Ravi Kant Head, Department of Obstetrics & Gynecology
Professor of Surgery, Safdarjung Hospital, New Delhi
Prevention of HIV infection
Investigations in a patient with early breast Dr. V.J.Anand
cancer Consultant Surgeon, New Delhi
Dr. S.Thomas
Professor of Surgery, Treatment of HIV infection
Lady Hardinge Medical College, New Delhi Dr. M.K.Daga
Professor of Medicine,
Surgical options in early breast cancer Maulana Azad Medical College, New Delhi
Dr. Gaurav Agarwal
Additional Professor of Endocrine Surgery, Counseling & voluntary testing
SGPGIMS, Lucknow Dr. Suneela Garg
Professor of Community Medicine,
Other treatment modalities in early breast Maulana Azad Medical College, New Delhi
cancer
Dr. K.Geeta Investigations for upper limb ischaemia
Consultant Breast Surgeon Dr. Anju Garg
Rajiv Gandhi Cancer Institute, New Delhi Professor of Radiodaignosis,
Surgery for hypernephroma
Dr. Atul Goswami Thoracic outlet syndrome
Consultant Urologist & Andrologist, Dr. M.P.Arora
Northex Stone Clinic, New Delhi Professor of Surgery,
Lady Hardinge Medical College, New Delhi
4
Management of acute upper limb ischaemia Surgery in ulcerative colitis
Dr. R.Parakh Dr. V.K.Kapoor
Chairman, Department of Vascular Surgery, Head Of Surgical Gastroenterology,
Sir Ganga Ram Hospital, New Delhi SGPGIMS, Lucknow
Management of chronic upper limb ischaemia Precancerous conditions

Dr. Kumud Rai Dr. Vijay Arora
Director, Vascular Surgery, Chairman, Department of General Surgery,
Max Heart & Vascular Institute, New Delhi Sir Ganga Ram Hospital, New Delhi
Surgeons‟ Viewpoint: Technological advances
have changed the surgeons‟ approach Pre-operative bowel preparation
Dr. Vivek Agrawal
Dr. A.K.Hemal Professor of Surgery,
Professor of Urology, University College of Medical Sciences, Delhi
All India Institute of Medical Sciences,
New Delhi Sphincter saving surgeries for rectal cancers
Dr.Parul J.Shukla
Scientific basis of clinical features of Intestinal In-Charge & Consultant HPB
obstruction & GI Surgical Oncologist,
Dr. S.K.Jain GI Surgical Service,
Associate Professor of Surgery, Department of Surgical Oncology,
Maulana Azad Medical College, New Delhi Tata Memorial Hospital, Mumbai
Congenital ano-rectal anomalies Adjuvant therapy for rectal cancers

Dr. S.K.Agrawal Dr. P.K.Julka
Professor of Paediatric Surgery, Professor of Radiation Oncology
Maulana Azad Medical College, New Delhi Institute-Rotary Cancer Hospital
All India Institute of Medical Sciences,
Ileocecal tuberculosis New Delhi
Dr. D.Bhatnagar
Head & Senior Consultant Management of recurrent rectal cancer
Department of Surgery, Dr. A.Bhatnagar
Safdarjung Hospital, Head and Senior Consultant
New Delhi Department of Cancer Surgery,
Safdarjung Hospital, New Delhi
Surgical complications of amebiasis
Dr. Rajeev Kapoor Management of anal cancers
Professor & Head & Incharge, Dr. A.K.Bahadur
Colorectal & General Surgery Unit, Professor and Head of Radiotherapy,
Christian Medical College and Hospital, Maulana Azad Medical College, New Delhi
Ludhiana
Scientific basis of clinical features of ano-rectal
Perianal fistulae diseases
Dr. B.K.Jain Dr. P.N.Agarwal
Professor and Head of Surgery, Professor of Surgery,
University College of Medical Sciences, Delhi Maulana Azad Medical College, New Delhi
5
Dr.B.S.Rana Memorial Oration, 2007
Computer assisted robotic urologic surgery
Dr. Narmada P.Gupta

Professor and Head,
Department of Urology,
AIIMS, New Delhi
Urologists are pioneer in endoscopy and started endoscopic surgery more than 100 years back
followed by endourologic, Laparoscopic and now Robotic Urologic Surgery. During the last 7 years,
significant progress had been made in robotic assisted laparoscopic surgery and a new standard of
care has been set up for many Urologic diseases.
The term robot was first coined by Karel Capek in 1921 in his play Rossums Universal Robots. The
robot word was derived from the Czech word ―Robota‖ meaning “Industrial worker”. It has gained
popularity through science fiction such as Blade Runner & Star Wars. The robots are in use in every
walk of our life and now are introduced in our operation theatre1.
A robot can be defined broadly as a mechanical device that is controlled using a computer system.
The first medical specialities to use robots were neurosurgery and orthopaedics. Robotic systems
were developed for neuronavigation, stereotactic localization, and robotic assistance. Neuro Mate is
commercially available FDA approved device. In Orthopaedics, the Robodoc was developed for
placement of prosthetic joints. Robots became popular in cardiac surgery for coronary bypass
surgery. In general surgery, clinical trials were performed for cholecystectomies, Nissen fundoplication
and recently in bariatric surgery. In gynaecology, it is used for reversal of tubal ligation, vault prolapse
etc.
The first Urologic surgery with the assistance of robot was a transurethral resection of prostate
performed by Wickham in 1979, however due to uncontrolled resection and bleeding, this has not
become popular. In Italy, robot was used to perform TRUS guided biopsy but did not provide any
advantage. At John Hopkins Medical centre, Percutaneous access to the Kidney (PAKY) was
developed with the assistance of robot and the system is currently being evaluated clinically.
Automated Endoscopic System for Optimal Positioning (AESOP) was the first active robotic device
approved by the FDA. AESOP is a robotic arm with motorized joints that is controlled by a surgeon
through the speech recognition system. Endo-Assist is a similar device, but the arm is controlled by
the surgeon‘s head movement. These devices have paved the way for Master Slave devices (da Vinci
Surgical system), which is at present manufactured only by Intitutive Surgicals, USA. A group of
urologists in 1996 in France started robotic radical prostatectomy but it was popularized by Mani
Menon from Detroit, USA in 2001. Today, there are more than 600 da Vinci robots installed all over
the world and mainly used in Urologic surgery. After seeing the success in Urology, other surgical
specialities have started exploring its utility.
da Vinci surgical system
The da Vinci surgical system consists of a surgeon‘s computer console for surgeon interaction, a
surgical cart that houses the video and lighting equipment, and a robotic tower that supports three or
four arms. The surgeon‘s console provides the user a three-dimensional view through a binocular
viewport. Interaction is through ―masters‖ in to which the surgeon inserts his or her hands. The
masters allow free movement that is translated intuitively in to seven degrees of freedom at the
robotic instruments tips. A double lens laparoscopic system is combined in to a single three
dimensional binocular view. The robotic tower supports three or four robotic with one arm controlling
the camera. Endowrist instruments come in a wide range of types including graspers, scissors, hook,
knives, hot scissors and surgical energy devices.
The master slave system has advantages of an ergonomic environment for performing surgery for the
surgeon. Surgeon can make natural hand movements rather than counter intuitive movements. It
6
filters hand tremors and scale movements, by digitizing surgeon‘s hand movements. The robotic arms
provide additional degree of freedom inside the patient‘s body. It provides 3-D view of the surgical
field & improves depth perception. With the seven degree of freedom at the instrument tips and 3-D
view, suturing becomes much simpler in comparison to laparoscopic surgery.
The port placement is important in robotic surgery to avoid robotic arm collisions. The robotic arms
are heavy and there should be a minimum gap of 8 cms between the ports. The camera port and
other robotic ports should be in triangulation for easy suturing. There is lack of tactile sensation in
robotic surgery which is compensated by magnification and visuals.
The Patient‘s advantage of robotic surgery is that it is a minimally invasive procedure with less
morbidity, shorter hospital stay and early return to work.
The disadvantage of robotic surgery is the initial cost of equipment and cost of reusable robotic
instruments. At present, the usage is limited to only 10 per instruments as a result cost of the surgery
is too much. This is the biggest limiting factor for robotic surgery in India. It is hoped that the cost will
come down in future to make robotic surgery affordable to a large number of patients. As any new
procedure, there is a learning curve in the robotic surgery, however in comparison to laparoscopic
surgery, there is a short learning curve for the complex urological procedures. The duration of surgery
is same as for open surgery and initially longer during the learning. The comparative trials are going
on to find out the efficacy and effectiveness of robotic surgery in comparison to open and laparoscopic
surgery. At present, there are no training facilities in India. We should have facilities for dry and wet
animal lab facilities for training in robotic surgery.
Our experience
The department of Urology at AIIMS, New Delhi purchased 4 arm da Vinci-S surgical system and
started robotic surgery since 19th July, 2006. Table 1 shows our experience during the last 1 year. We
have performed 181 procedures on 177 patients. The commonly done procedures are Robotic
Radical prostatectomy in 74 patients followed by Robotic pyeloplasty in 44 cases. Apart from
reconstructive procedures, we have also done ablative procedures like Radical cystectomy and
extracorporeal diversion, Nephrectomy, Nephroureterectomy, Ureteric reimplantation, VVF repair,
pyelolithotomy etc. etc. We have found advantages in reconstructive procedures like Radical
prostatectomy and pyeloplasty. Table 2 to 8 summarizes published data from the literature and
compares with our own.
Conclusion
Robotic surgery is a significant advance in the realm of urologic surgery esp. for robotic
prostatectomy, robotic pyeloplasty and is under evaluation for other procedures. Robotic surgery is
associated with precision and ease in dissection, incision and suturing with less steep learning curve
in comparison to laparoscopy. It provides all benefits of minimally invasive surgery. At present, cost is
a prohibitive factor. Robotic surgery is going to stay and is going to open new avenues for
telepresence surgery.
7
Table 1 - Experience of robotic procedures at AIIMS
(177 Patients, 181 Procedures)
Ablative Reconstructive Miscellaneous
Rad nephrectomy - 7 Radical prostatectomy - 74 Extended Pyelolithotomy -

(1-cholecystectomy) Radical Cystectomy - 16 4
Nephroureterectomy - 3 Diverticulectomy with Pyeloplasty with
Simple nephrectomy - 3 ureteric reimplantation - 1 pyelolithotomy - 7
Nephrolithotomy - 1
Adrenalectomy - 2 Pyeloplasty – 44 (1- B/L) Uretero-vesico lympholysis
Bladder diverticulectomy - 1 Ureteropyelostomy with - 1 (B/L)
pyelolithotomy - 1 Ureterolysis - 1
Ureteroureterostomy - 1
VVF – 5 Ureteric reimplantation - 5
(1-B/L)
Table 2 - Robotic Radical Prostatectomy – Basic parameters
Prostate
FU Age PSA
Series Year Number BMI Volume G 2.5 G6 G7 G 8-10
Duration (Years) (ng/mL)
(mL)
G 6 or G 6 or
less less
38 4
Tseng2 2006 90 NA 58.2 28.6 5.9 47.4 than than
(42%) (4.4%)
48 48
(53%) (53%)
25.5
15 61.3 11.5 34.4
Bentas3 2003 40 (20.7- NA NA NA NA
(11-23) (45-72) (0.5-53) (15-100)
31.4)
G 6 or G 6 or
28.1 52.5
Up to 9 61.4 7.3 less – less – 16
Ahlering4 2003 45 (20.2- (12.5- 7 (16%)
months (46-71) (1.1-24) 20 20 (36%)
39.4) 163)
(44%) (44%)
G 6 or G 6 or
26.3
62.9 8.1 52.5 (18- less – less – 14
Ahlering5 2004 60 3 (20.6- 9 (15%)
(43-78) (0.1-62) 135) 37 37 (23%)
33.6)
(62%) (62%)
Tewari 27.7
59.9 6.4 58.8 1 86 80 21
and 2003 200 7.9 (919-
(40-72) (0.6-41) (18-140) (0.5%) (43%) (40%) (10.5%)
Menon6 38)
67 8.9 67.6 (37-
Samadi7 2002 11 NA NA NA NA NA NA
(58-71) (3.9-32) 120)
G 6 or G 6 or
Weighted
373 61 27.3 7.6 53.8 less less 35.71% 12.15%
Means
47.51% 47.51%
25.2 23.5
Our 6.5 64.1 41 (15-
2007 63 (16- (0.95- 10 32 13 5
series months (50-76) 165)
34) 89)
8
Table 3 - Robotic Radical Prostatectomy - Operative Parameters
Total
Hosp Catheter
Installation Operative OR EBL Blood Conversion /
Series Stay Duration
Time (min) Time (min) Time (Ml) Transfusion Abortion
(Days) (days)
(min)
800
93 222 5.5 6.5
Pasticier8 NA (700- 0 0
(76-149) (150-381) (4-7) (5-9)
1600)
594 570
500 13 2 17.1 16.7
Bentas3 NA (288- (100-
(246-780) (32.5%) (5%) (6-32) (5-49)
930) 2500)
1013
274 2.7
Gettman9 NA NA (550- NA 0 5.3
(1424-360) (2-3)
1500)
Kaouk10 NS 285 NA 300 0 0 2 21
145
23 209 228 1.6
Ahlering4 (25- 0 0 7
(15-40) (150-600) (NA) (1-7)
350)
231 103
1.1
Ahlering5 NA NA (160- (25- 0 0 7
(0.75-4)
340) 400)
153
Tewari and 160 2 1.2 7
NA NA (25- 0
Menon6 (71-315) (1%) (<1-5) (1-18)
750)
Weighted 0.3% 1.4
32 222 331 231 1.1% 8.1
Means (3.9%) (3.1)
19 (port
placement 3 (post-op)
Our series 159 204 170 2 3.5 12
and
docking)
Table 4. Robotic Radical Prostatectomy - Pathologic Parameters
Series pT2a pT2b pT3a pT3b pT4 LN+ SM+

8
Pasticier 2 (40%) 3 (60%) 0 0 0 NA 1 (20%)
Bentas3 7 (18%) 18 (45%) 9 (22%) 6 (15%) 0 NA 12 (30%)

4
Ahlering 6 (13%) 21 (47%) 11 (24%) 5 (11%) 1 (2%) NA 16 (35%)
Ahlering5 16 (27%) 29 (48%) 10 (17%) 4 (7%) 1 (1%) NA 10 (17%)

Tewari and
30 (15%) 144 (72%) 14 (7%) 12 (6%) 0 2 (1%) 12 (6%)
Menon6
Samadi7 5 (45%) 3 (27%) 2 (18%) 1 (9%) 0 1 (9%) 3 (27%)
Weighted
18% 61% 14% 7.5% 0.5% 0.8% 15%
Means
Our series 20 (31.7%) 32 (50.8%) 7 (11.1%) 4 (6.4%) 0 2 (3.1%) 6 (9.5%)
9
Table 5. Robotic Radical Prostatectomy – Morbidity and Mortality
Series Minor Complications Major Complications Mortality
8 (20%) 2 venous bleeding 5 (12.5%) 2 PE
Bentas3 4 anastomotic leak 1 DVT 0
2 UTI 1 obturator N injury
Gettman9 0 0 0
Kaouk10 0 0 0
3 (7%) 1DVT
4 3 (7%) 2 anastomotic leaks
Ahlering 1 anastomotic disruption 0
1 port site bleeding
1 leg neuromuscular injury
2 (3%)1 anastomotic leak 2 (3%) 1 PE
Ahlering5 0
1 ileus 1 delayed anastomotic bleed
4 (2%) 2 wound dehiscence / hernia
Tewari and
3 (1.5%) 3 ileus 1 DVT 0
Menon6
1 post-op bleeding
Samadi7 0 0 0
Weighted Means 4.55% 3.75% 0
2 (3.2%) 1 adhesive intestinal
obstruction requiring laparoscopic
3 (4.7%) 3 anastomotic leak
Our series re-exploration 0
2 ileus
1 ascites and peritoneal urinary
spillage requiring SPC
Table 6. Robotic Radical Prostatectomy – Postoperative Continence

Follow- 2 or
Total Number Age Evaluation
Series up Continent 0 Pads 1 Pad More
Number Evaluated (Years) Method
(Months) Pads
61.3 15 32 26 6
Bentas3 40 38 Questionnaire 6 (16%)
(45-72) (11-23) (84%) (68%) (16%)
61.4 NA NA NA NA
Ahlering4 45 NA 3 Questionnaire
(46-71) (95%) (81%) (14%) (5%)
62.9 NA
Ahlering5 60 NA 3 Questionnaire NA NA NA
(43-78) (76%)
NA NA (4%)
Menon
59.9 NA (96%) [0 [1 or
and 200 NA 6 Questionnaire NA
(42-76) (96%) pad or 1 more
Tewari6
liner] pads]
Weighted
245 NA 60.8 6.1 Questionnaire 94% 87.5% 7% NA
Means
Our 50 (1 pre-op 63.7

63 3 Questionnaire 92 % 43 3 4
series incontinent) (50-76)
10
Table 7. Robotic Radical Prostatectomy - Postoperative Sexual Function
Number
Total Number FU Evaluation
Series Potent Age UNS BNS Potent Intercourse
Number Evaluated (months) Method
Preop
61.3
3 15 8
Bentas 40 38 37 (45- NA MA Questionnaire
(11-23) (22%)
72)
57.3
5 1
Ahlering 45 9 3 (54- 2 (66%) Up to 9 Questionnaire 1 (33%)
(33%)
59)
Menon Only preop
NA
and 200 potent NA <60 NA NA 6 Questionnaire NA (64%)
6 (64%)
Tewari patients
11 59 7 NA
Chien 16 16 16 9 (56%) NA 8 (50%) 5 (31%)
(NA (44%) (1-10)
Weighted
301 59.6 7.7 46.5% 49.5%
Means
50 (13 pre-
op
63.7
Our impotent/ 11
63 28 (50- 3 Questionnaire 4 (14.3%)
series no active (39.2%)
76)
sexual
life)
Table 8. Robotic Pyeloplasty

Length of
No of Op time Suturing Blood Follow up Success
Complications hospital
patients (mins) time (mins) loss (ml) (mths) rate
stay (days)
Weise and
31 271 76 < 100 6% 2.1 6 97%
Winfield
12
Patel V 50 122 20 40 Nil 1.1 11.7 100%
Mendez et Not
13 32 300 50 6% 1.1 8.6 100%
al available
Siddiq et al 26 245 47 69 13% 2 6 95%
Palese et al 35 216 63 74 11% 2.9 7.9 94%
Not Not
Peschel et al 49 124 <50 2% 7.4 100%
available available
Current
47 130 47 53 8.5% 2.5 8.2 94.3%
series
References
1. Kumar R, Hemal AK, Menon M. Robotic renal and adrenal surgery: present and future. BJU Int. 2005; 96(3): 244-9
2. Tseng TY, Kuebler HR, Cancel QV, et al. Prospective health-related quality of life assessment in an initial cohort of
patients undergoing robotic radical prostatectomy. Urology. 2006; 68(5): 1061-5
3. Bentas W, Wolfram M, Jones J. Robotic technology and translation of open radical prostatectomy to laparoscopy: the
early Frankfurt experience with robotic radical prostatectomy and one year follow up. Eur Urol. 2003; 44(2): 175-81
4. Ahlering TE, Skarecky D, Lee D, Clayman RV. Successful transfer of open surgical skills to a laparoscopic environment
using a robotic interface: initial experience with laparoscopic radical prostatectomy. J Urol. 2003; 170(5): 1738-41
5. Ahlering TE, Woo D, Eichel L, Lee DI, Edwards R, Skarecky DW. Robot assisted versus open radical prostatectomy: A
comparison of one surgeon‘s outcomes. Urology. 2004; 63(5); 819-822
6. Tewari A, Srivasatava A, Menon M, et al: A prospective comparison of radical retropubic and robot-assisted
prostatectomy: experience in one institution. BJU Int 2003; 92(3): 205-10
7. Hoznek A, Samadi DB, Salomon L, et al. Laparoscopic radical prostatectomy. Curr Urol Rep. 2002; 3(2): 141-7
8. Pasticier G, Rietbergen JB, Guilloneau B, et al. Robotic assisted robotic radical prostatectomy: feasibility study in men.
Eur Urol. 2001; 40(1): 70-4
9. Gettman MT, Hoznek A, Salomon L, et al. laparoscopic radical prostatectomy: description of the extraperitoneal approach
using the da Vinci robotic system. J Urol. 2003; 170(2 pt 1): 416-9
10. Hegarty NJ, Kaouk JH. Radical prostatectomy: comparison of open, laparoscopic and robotic assisted laparoscopic
techniques. Can J Urol. 2006; 13(1): 56-61
11. Chien GW, Mikhail AA, Orvieto MA, et al. Modified clipless antegrade nerve preservation in robotic assisted laparoscopic
radical prostatectomy with validated sexual function evaluation. Urology. 2005; 66(2): 419-23
12. Patel V. Robotic-assisted laparoscopic dismembered pyeloplasty. Urology 2005; 66: 45-49
13. Mendez-Torres F, Woods M, Thomas R. Technical modifications for robot assisted laparoscopic pyeloplasty. J Endourol
2005; 19: 393-6.
11
Intercostal tube management: Guidelines
Dr. Ajit Sinha
Introduction
Drainage of the pleural space by means of a chest tube is the commonest intervention in thoracic
trauma.
Hippocrates was the first physician to use a chest tube; he inserted a metal tube into a patient‘s
pleural space to drain an empyema. Today, typically chest tube is inserted to remove air or fluid from
the pleural space. The pleural space lies between the visceral and the parietal pleura. Normally this
potential space holds about 50ml of lubricating fluid that prevents friction between the pleurae as they
move during inhalation and exhalation.
For various reasons, excess fluid or air may accumulate in the pleural space. Small volumes can be
absorbed by the body over time, but large volumes limit lung expansion. As a result, the patient
experiences shortness of breath and increase in respiratory rate and effort.
Inserted into the pleural space, a chest tube can drain air or excess fluid and relieve respiratory
distress. Typically a small bore chest tube (12-20 French) is adequate to remove a small amount of
air, but for adults, a larger bore tube (24 to 40 French) is usually needed to remove excess fluid or
blood and larger amounts of air.
Chest tube provides definitive treatment in the majority of cases. While a relatively simple procedure,
it carries a significant complication rate reported as between 2% and 10%. While many of these
complications are relatively minor, some require operative intervention and death still occurs.
Chest tube indications
Pneumothorax : Air in the pleural space.

may be due to trauma, lung disease, invasive pulmonary
procedure, forceful coughing, surgical complication and
sometimes may occur spontaneously.
Haemothorax : Blood in the pleural space.

Blunt or penetrating trauma, complication of chest surgery,
If it is also combined with air in the pleural space, it is
called Haemopneumothorax.
Pleural effusion : Excess fluid in the pleural space.

Pneumonia, cancer, tuberculosis, complication of surgery,
left Ventricular failure, pulmonary embolism.
Chylothorax : Lymphatic fluid.

Chest trauma, expanding tumour or surgery on mediastinal
structures.
Empyema : Pus. Must be drained, no matter how small the volume

because purulent fluid damages the pleural membrane.
Prophylactic : After thoracic and cardiac surgery, sometimes after chest

trauma
: To prevent tension pneumothorax in the ventilated patient
with rib fractures.
Miscellaneous : To instil fluids into the pleural space---cancer

chemotherapy, Sclerosing agents (pleurodesis).
12
Pre chest tube insertion assessment
Physical signs to look for:-

1. Respiratory Rate and Respiratory distress.
2. Tracheal Deviation (away from the affected side).
3. Decreased breath sounds.
4. Crepitus, Subcutaneous emphysema.
5. Distended neck veins or systemic hypotension (cardiac tamponade or tension pneumothorax.
6. Paradoxical movements.(flail chest occurs when four or more ribs are fractured in at least two
locations).
Chest X-ray:-
In most cases will identify a pneumothorax or a haemothorax and is obtained before placing a chest
tube. A haemothorax may also be identified on FAST Ultrasound.
However, there are instances where the patient is in extremis and it is appropriate to place a chest
tube without waiting for imaging studies. Patients in traumatic arrest with no cardiac output should
have immediate decompression of both chest hemithoraces to exclude tension pneumothorax.
Similarly, patients in shock or profound hypoxia with unilateral chest signs or evidence of penetrating
trauma to a hemithorax should have a chest tube placed emergently.
Before insertion, air or fluid should be aspirated and if none is forthcoming more complex imaging like
fluoroscopy, ultrasonography and CT Scanning can be used as guides to the site of tube placement.
Equipment
All the equipment required to insert a chest tube should be available before commencing the
procedure.
Sterile gloves and gown

Skin antiseptic solution e.g. Iodine or chlorhexidine in alcohol
Sterile drapes
Gauze swabs
A selection of syringes and needles (21 – 25 gauge)
Local anaesthetic e.g. Lignocaine 1% or 2%
Scalpel and blade
Suture e.g. ―1‖ silk
Instrument for blunt dissection (e.g. Curved clamp)
Chest tube
Connecting tubes
Closed drainage system (including sterile water for under water seal)
Dressing.
Consent and premedication
Prior to commencing chest tube insertion, the procedure should be fully explained to the patient and
written consent taken.
Chest drain insertion has been reported to be a painful procedure with 50% of patients experiencing
pain levels of 9-10 on a scale of 10 in one study. Hence unless there are contraindications, painkillers
should be given to reduce patient distress.
13
Patient position
The preferred position for drain insertion is on the bed, slightly rotated, with the arm on the side of the
lesion behind the patient‘s head to expose the axillary area.
An alternative is for the patient to sit upright leaning over an adjacent table with a pillow or in the
lateral decubitus position.
Insertion site
Insertion should be in the ―SAFE‖ triangle illustrated in Figure 1. This is the triangle bordered by the
anterior border of the latissimus dorsi, the lateral border of pectoralis major muscle, a line superior to
the horizontal level of the nipple and an apex below the axilla.
This position minimizes risk to underlying structures such as the internal mammary artery and avoids
damage to muscle and breast tissue resulting in unsightly scarring. A more posterior position may be
chosen if suggested by the presence of a locule. While this is safe, it is not the preferred site as it is
more uncomfortable for the patient to lie on after insertion and there is a risk of the drain kinking.
For apical pneumothoraces, the second intercostal space in the midclavicular line is sometimes
chosen but is not recommended routinely as it may be uncomfortable for the patient and may leave an
unsightly scar.
Aseptic technique
As a chest drain may potentially be in place for a number of days, aseptic technique is essential to
avoid wound site infection or secondary empyema. Estimations of the empyema rate following drain
insertions for trauma are approximately 2.4%.
Full sterile technique afforded by a surgical theatre is usually unnecessary; sterile gloves, gown,
equipment and use of sterile towels after effective skin cleaning using iodine or chlorhexidine are
recommended. A large area of skin cleansing should be undertaken. In a study of chest tubes
inserted in trauma suites using full aseptic technique, there were no infective complications in 80
cases.
Anaesthesia
Local anaesthetic is infiltrated into the site of insertion of the drain. A small gauge needle is used to
raise a dermal bleb before deeper infiltration of the intercostal muscle and pleural surface. A spinal
needle may be required in the presence of a thick chest wall.
Local anaesthetic such as lignocaine (up to 3 mg/kg) is usually infiltrated. The volume given is
considered to be more important than the dose to aid spread of the effective anaesthetic area, hence
1% solution infiltration is recommended.
14
Insertion of the chest tube
After infiltrating insertion site with local anaesthetic, make a 3-4 cm incision through skin and
subcutaneous tissues between the 4th and 5th ribs, parallel to the rib margin.
Continue incision through the intercostal muscles, and right down to the pleura.
Insert Kelly clamp (curved artery forceps) and open the jaws widely, again parallel to the direction of
the ribs. (this ―creates‖ a pneumothorax, and allows the lung to fall away from the chest wall. This step
should be performed without substantial force thus avoiding sudden chest penetration and damage to
essential intrathoracic structures.
Insert finger through the incision and into the thoracic cavity, making sure an empty space is felt and
blunt dissection into the pleural space must be performed before insertion of a large bore test tube.
15
Grasp end of the chest tube with the Kelly forceps. (convex angle towards ribs) and the chest tube is
inserted through the hole made in the pleura. After the tube has entered thoracic cavity, Kelly is
removed and the tube is advanced manually.
The position of the tip of the chest tube should ideally be aimed apically for a pneumothorax or basally
for fluid. However any tube position can be effective at draining air or fluid and an effectively
functioning drain should not be repositioned simply because of a suboptimal radiographic
appearance.
Securing the chest tube
Two sutures are usually inserted. The wound closure suture should be inserted before blunt
dissection. A strong suture such as ―1‖ silk is appropriate. A ―mattress‖ suture or sutures across the
incision are usually employed. Complicated ―purse string‖ sutures must not be used as they convert a
linear wound into a circular one that is painful for the patient and may leave unsightly scar.
The drain should be secured with stout non absorbable suture taking adequate skin and
subcutaneous tissue. Large amount of tape or padding to dress the site are unnecessary.
16
MANAGEMENT OF THE DRAINAGE SYSTEM
Closed System Drainage
The chest tube is then attached to a drainage system which only allows one direction of flow. This is
usually the closed underwater seal bottle in which a tube is placed under water at a depth of
approximately 3cm with a side vent which allows escape of air, or it may be connected to a suction
pump.
Underwater seal enables to see air bubble out as the lung re-expands in the case of pneumothorax or
fluid evacuation rate in empyema, pleural effusion or haemothorax.
The continuation of bubbling suggests a continued visceral pleural air leak. The respiratory swing in
the fluid in the chest tube is useful for assessing tube patency and confirms the position of the tube in
the pleural cavity. The disadvantages of the underwater seal system include obligatory inpatient
management, difficulty of patient mobilization, and risk of knocking over the bottle.
Following Precautions to be taken:-

 A bubbling chest tube should never be clamped—tension pneumothorax.
 Drainage of a large pleural effusion should be controlled to prevent the potential
Complication of re-expansion pulmonary oedema.
 In cases of pneumothorax, clamping of the chest tube should be avoided.
 If a patient with a clamped drain becomes breathless or develops subcutaneous emphysema,
the drain must be immediately unclamped and medical advice sought.
Suction
The use of high volume/ low pressure suction pumps has been advocated in cases of non resolving
pneumothorax, but there is no evidence to support its routine use in the initial treatment.
If suction is required, this may be performed via the underwater seal at a level of 10 – 20 cm H2O. A
high volume pump is required to cope with a large leak. A low volume pump is inappropriate as it is
unable to cope with rapid flow, thereby effecting a situation similar to clamping and risking formation
of a tension pneumothorax. A wall suction adapter may also be effective although chest drains must
not be connected directly to the high negative pressure available from wall.
17
Assessment
A chest radiograph should be performed after insertion of a chest drain to assess tube position, and
assess the success of the procedure in the volume drainage or pneumothorax reduction. Patients
should be managed on a ward familiar with chest tubes.
Due to underwater seal, instructions must be given to keep the bottle below the insertion site at all
times, to keep it upright, and to ensure that adequate water is in the system to cover the end of the
tube.
Daily re assessment of the amount of drainage/ bubbling and the presence of respiratory swing
should be documented, preferably on a dedicated chest drain chart.
Instruction with regard to chest drain clamping must be given and recorded. Patients should be
encouraged to take responsibility for their chest tube and do deep breathing exercises.
Removal of chest tube
The chest tube should be removed either while the patient performs Valsalva‘s manoeuvre or during
expiration with a brisk firm movement while an assistant ties the previously placed suture and
immediately applies sterile occlusive petroleum gauze to the wound to prevent air from entering the
pleural space.
Following criteria should be met before removing the drain:-

 The drainage has decreased to little or none.
 The air leak has disappeared.
 The patient is breathing normally without respiratory distress.
 Breath sounds are present at the base of lung.
 Fluctuation in the water seal chamber has stopped.
 A previous chest X-Ray shows lung re-expansion with no residual air or fluid in the
pleural space.
Monitor patient‘s respiratory status for 1 to 2 hours after removal and arrange to have a chest X-Ray
to assess for lung re-expansion.
Contraindication
Contraindications to chest tube placement include:

 Refractory coagulopathy
 Diaphragmatic Hernia.
Prophylactic antibiotics
Analysis of studies suggest that in the presence of chest trauma (penetrating or blunt), the use of
prophylactic antibiotics reduces the absolute risk of empyema by 5.5 – 7.1% and of all infectious
complications by 12.1 – 13.4%. Prophylactic antibiotics in trauma cases are, therefore, recommended.
The use of prophylactic antibiotics is less clear in the event of spontaneous pneumothorax or pleural
effusion drainage.
Complications
Major: Haemorrhage, Infection, and re-expansion pulmonary oedema, injury to the liver, spleen or
diaphragm is possible if the tube is placed inferior to the pleural cavity.
Injuries to the thoracic aorta and the heart have also been described.
18
Minor: Subcutaneous hematoma or seroma, anxiety, shortness of breath (dyspnoea) and cough
(after removing large volumes of fluid)
Major haemorrhage
Moderate ongoing bleeding from a blunt chest injury that will ultimately require operative intervention
is unusual however indications of thoracotomy are:
 Return of over 1500 ml of blood.
 Continuous loss at a rate of more than 250 ml/hour after a penetrating injury.
Major air leak

Continuous flow of air from a chest tube with inability to adequately ventilate, oxygenate or re-expand
the lung indicates a major injury to the airway. Bronchoscopy is necessary to determine the site of
injury and appropriate management. Injuries greater than one-third of the circumference of a bronchus
should be promptly repaired in the operating room.
Bibliography
1. American College of Surgeons Committee on Trauma.

2. Miller KS, Sahn SA. Review. Chest tubes .Indications, technique, management and complications.
3. Baumann MH. What size chest tube? What drainage system is ideal? And other Chest tube management
questions.
4. Morton PG, Fontaine D, eds, Critical care nursing, a holistic approach.
5. Spiegler P, et al. Rapid pleurodesis for malignant pleural effusions.
6. Tomlinson MA, Treasure T. Insertion of a chest drain: how to do it?
7. Luketich JD, Kiss MD, Hershey J, et al. Chest tube insertion: a prospective evaluation of pain management.
8. Parry GW, Morgan WE, Salama FD. Management of haemothorax.
9. Davis JW, MacKersie RC, Hoyt DB, et al. Randomised study of algorithms for discontinuing tube thoracostomy
drainage.
10. Fallon WF, Wears RL. Prophylactic antibiotics for the prevention of infectious complications.
11. Rashid MA, Wikstrom T, Ortenwall P. A simple technique for anchoring chest tubes.
12. Mafhood S, Hix WR, Aaron BIet al. re expansion pulmonary oedema.
13. Hall M Jones, A. Clamping may be appropriate to prevent discomfort and reduce risk of oedema.
14. Main A. As few sharp objects as possible should be used on entering pleural space.
19
Chest Trauma: Rib fractures & Flail Chest
Dr. S. Bal
Chest wall injury is an extremely common following blunt trauma. It varies in severity from minor
bruising or an isolated rib fracture to severe crush injuries of both hemithoraces leading to respiratory
compromise.
While many chest injuries will require no specific therapy, they may be indicators of more significant
underlying trauma. Multiple rib fractures will often be associated with an underlying pulmonary
contusion, which may not be immediately apparent on an initial chest X-ray. Fractures of the lower
ribs may be associated with diaphragmatic tears and spleen or liver injuries. Injuries to upper ribs are
less commonly associated with injuries to adjacent great vessels. This is especially true of a first rib
fracture, which requires a significant amount of force to break and indicates a major energy transfer. A
fracture of the first rib should prompt a careful search for other injuries. Note also that the rib cage and
sternum provide a significant amount of stability to the thoracic spine. Severe disruption of this ‗fourth
column‘ may convert what would otherwise be a stable thoracic spine fracture into an unstable one.
Flail Chest
A flail chest occurs when a segment of the thoracic cage is separated from the rest of the chest wall.
This is usually defined as at least two fractures per rib (producing a free segment), in at least two ribs.
A segment of the chest wall that is flail is unable to contribute to lung expansion. Large flail segments
will involve a much greater proportion of the chest wall and may extend bilaterally or involve the
sternum. In these cases the disruption of normal pulmonary mechanics may be large enough to
require mechanical ventilation. The main significance of a flail chest however is that it indicates the
presence of an underlying pulmonary contusion. In most cases it is the severity and extent of the lung
injury that determines the clinical course and requirement for mechanical ventilation. Thus the
management of flail chest consists of standard management of the rib fractures and of the pulmonary
contusions underneath.
Diagnosis
Most significant chest wall injuries will be identified by physical examination. Bruising, grazes or seat-
belt signs are visible on inspection, and palpation may reveal the crepitus associated with broken ribs.
Awake patients will complain of pain on palpation of the chest wall or on inspiration.
A flail chest is identified as paradoxical movement of a segment of the chest wall - i.e. in-drawing on
inspiration and moving outwards on expiration. This is often better appreciated by palpation than by
inspection.
Chest X-ray
The antero-posterior chest radiograph will identify most significant chest wall injuries, but will not
identify all rib fractures. Lateral or anterior rib fractures will often be missed on the initial plain film.
However, since the management of rib fractures is determined by their clinical significance rather than
by their number or position, dedicated rib views are never indicated.
For adult blunt trauma patients, a haemothorax, pneumothorax or pulmonary contusion seen on chest
X-ray will almost always be associated with a rib fractures, whether or not identified clinically or by X-
ray. In paediatric patients the ribs are more pliable and less likely to fracture, although there will still
be significant contusion of chest wall structures.
Management
Management of chest wall injury is directed towards protecting the underlying lung and allowing
adequate oxygenation, ventilation and pulmonary toilet. This strategy is aimed at preventing the
development of pneumonia, which is the most common complication of chest wall injury. Note that
while a young fit patient will easily manage one or two rib fractures with simple analgesia, the same
injury in an elderly patient is regarded as major and will frequently lead to pneumonia and respiratory
failure if not appropriately managed (and even then).
20
All patients should initially be placed on 100% oxygen via a non-rebreathing facemask.
Analgesia
Analgesia is the mainstay of therapy for rib fractures. While strapping the chest to splint rib fractures
may seem like a good idea, it impedes chest wall movement and prevents adequate inspiration and
clearance of secretions. Opioid analgesics are useful, but when used as the sole analgesic agent may
require such high doses that they produce respiratory depression - especially in the elderly. Patient
controlled administration of an opioid infusion (PCA) is the best method for cooperative patients. The
addition of a non-steroidal anti-inflammatory agent may provide adequate relief, but these should be
withheld until other injuries have been excluded (e.g. traumatic brain injury) and used with caution in
the elderly.
Undoubtedly the best analgesia for a severe chest wall injury is a continuous epidural infusion of a
local anaesthetic agent (+/- an opioid). This provides complete analgesia allowing normal inspiration
and coughing without the risks of respiratory depression. Epidurals may be placed in the thoracic or
high-lumbar positions.
Other methods of local anaesthetic administration are available, but are poor in comparison to an
epidural. For one or two isolated rib fractures, posterior rib blocks may be appropriate. Local
anaesthetic is infiltrated around the intercostal nerve posteriorly. These blocks will last 4-24 hours and
will then have to be repeated. Where a chest tube is present, some practitioners advocate instilling a
local anaesthetic solution into the pleural space. However the volume needed is large, the results very
variable, and local anaesthetic toxicity due to rapid pleural absorption a possibility.
Intubation and Ventilation
Intubation and mechanical ventilation is rarely indicated for chest wall injury alone. Where ventilation
is necessary it is usually for hypoxia due to underlying pulmonary contusions. Positive pressure
ventilation may be required for severe chest wall instability resulting in inadequate spontaneous
ventilation. Intubation and ventilation may be required when anaesthesia is necessary to provide
immediate and adequate analgesia and allow further assessment and management.
Ventilation is usually necessary only until the resolution of the pulmonary contusion. Healing and
stabilisation of rib fractures is rarely the limiting step in weaning from mechanical ventilation, except in
the most severe chest injuries.
Chest tube insertion
Patients with rib fractures who receive positive pressure ventilation are at an increased risk of
developing a pneumothorax or tension pneumothorax due to laceration of the lung by the sharp
fracture end. Many authors recommend placement of a prophylactic chest tube for all patients with rib
fractures who receive mechanical ventilation. This practice varies depending on the presence of other
injuries, monitoring environment and available resources. For example, the patient with isolated chest
injuries with continuous cardiorespiratory monitoring in an intensive care unit can probably be
observed without a chest tube. In contrast, in a patient anaesthetised for prolonged surgery,
placement of a prophylactic chest tube may be more appropriate. Especially where the signs of a
tension pneumothorax may be mistaken for signs of haemorrhagic shock.
Rib fracture fixation
The popularity of rib fracture fixation has waxed and waned over the past 5 decades. External fixation
and stabilisation was common for large chest wall injuries prior to the development of tracheal
intubation and mechanical ventilation.
Positive pressure ventilation essentially provides an 'internal stabilisation' to the thoracic cage as well
as improving oxygenation and ventilation for the management of pulmonary contusion. Hence it has
essentially replaced fracture fixation over the past twenty years. In the last few years however a few
studies have suggested that some groups of patients (as yet unidentified) may benefit from early
21
fracture fixation, allowing earlier weaning from mechanical ventilation and reducing acute
complications and chronic chest wall pain.
References
Rib fractures
1. Ziegler DW, Agarwal NN. The morbidity & mortality of rib fractures. J Trauma 1994;37:975
2. Dubinsky I, Low A. Non-life-threatening blunt chest trauma: appropriate investigation and treatment. Am J Emerg
Med 1997;15:240
3. Lee RB, Bass SM, Morris JA Jr et al. Three or more rib fractures as an indicator for transfer to a level 1 trauma
center: a population-based study. J Trauma 1990;30:689
4. Flail Chest
5. Clark GC, Schecter WP, Trunkey DD. Variables affecting outcome in blunt chest trauma: Flail chest vs. pulmonary
contusion. J trauma 1990;30:93
6. Freedland M, Wilson RF, Bender JS. The management of flail chest injury: Factors affecting outcome. J Trauma
1990;30:1460
7. Pelosi P, Cereda M, Foti G. Alterations of lung and chest wall mechanics in patients with acute lung injury: effects
of positive end-expiratory pressure. Am J Resp Crit Care Med 1995;152:531
8. Craven KD, Oppenheimer L, Wood LD. Effects of contusion and flail chest on pulmonary perfusion and oxygen
exchange. J Appl Physiol 1979;47:729
9. Landercasper J, Cogbill T, Lindesmith L. Long-term disability after flail chest injury. J Trauma 1984;24:410
Analgesia
1. Hedderich R, Ness T. Analgesia for trauma and burns. Crit Care Clin 1999;15:167
2. Desai P. Pain management & pulmonary dysfunction. Cri Care Clin 1999;15:151
3. Mackersie RC, Shackford SR, Hoyt DB et al. Continouous fentanyl analgesia: ventilatory function improvement
with routine use in treatment of blunt chest injury. J Trauma 1987;27:1207
Rib fracture fixation

1. Tanaka H, Yukioka T, Yamaguti Y et al. Surgical stabilization of internal pneumatic stabilization? A prospective
randomized study of management of severe flail chest patients. J Trauma 2002;52:727
2. Ahmed Z, Mohyuddin Z. Management of flail chest injury: internal fixation versus endotracheal intubation and
ventilation. J Thorac Cardiovasc Surg 1995;110:1676
3. Voggenreiter G, Neudeck F, Aufm'Kolk M et al. Operative chest wall stabilization in flail chest - outcomes of
patients with and without pulmonary contusion. J Am Coll Surg 1998;130:187
22
Splenic injuries
Dr. Arun Gupta
Splenectomy for injuries to the spleen, even if trivial in nature, remained the standard treatment for
most of the twentieth century. There has been a shift in the management of trauma to the spleen,
however, over the last few decades. This originated from the observation that Splenectomy was
accompanied by an increased risk of sepsis, especially in children, which was given the name of
overwhelming post-splenectomy infection (OPSI). Surgeons who regarded the risk of infection very
significant argued strongly for conservative management of splenic trauma and adopted
splenorrhaphy as a method of splenic salvage. Today, non-operative management of splenic injuries
(NOMSI) has replaced splenorrhaphy as the most common method of splenic preservation1. There
can be, however, dangerous failures of this management. Most of these failures manifest as drop in
the haemoglobin. In some, the patients can become acutely hemodynamically unstable and some of
these patients will die. Are these events predictable and preventable? Are we putting patients at risk
by non-operative therapy?
Post-splenectomy sepsis
In 1919 Morris and Bullock2 in an experimental study had shown that 50% of splenectomized rats
when infected with bacillus of rat plague died as compared to 11% of the control group. They had
concluded that spleen aided in resisting infection. Much later in 1952 King and Shumacker reported
cases of severe infection in infants who had undergone Splenectomy for spherocytosis3. In 1969
Diamond4 introduced the term overwhelming post-splenectomy infection (OPSI) where they observed
that the infection begins as slight sore throat or fever proceeding to headache, vomiting and
hyperpyrexia and is followed in a very few hours by convulsions or coma and death. From 1952 to
1987 all the reported cases of splenectomy, which made a reference of infection as a complication,
were analysed and presented as a review5. Among the 12514 patients undergoing Splenectomy for all
reasons there was a 3.6% incidence of severe infection and 1.8% incidence of death. The infection
rate in children (<16yrs) was 4.4% with a mortality of 2.2%. The infection rate in those above 16yrs of
age was 0.9% with a mortality of 0.8%. When only patients undergoing splenectomy for trauma were
analysed the incidence of post-splenectomy infection was 2.0% in patients less than 16 yrs but no
infection was seen in patients more than 16 yrs of age. A significant observation of this review was
that almost all the published literature is retrospective in nature and there is a need to have
prospective longitudinal studies in patients undergoing splenectomy to resolve the issue.
Non-operative Management of splenic injuries
With reports of OPSI in the later part of the twentieth century methods of splenic salvage developed.
Improvements in computed tomography (CT) imaging for evaluation of haemoperitoneum and intra-
abdominal organ injuries has been the fundamental to this shift in practice. Non-operative
management of splenic injuries (NOMSI) is currently used in up to 70% of patients with documented
injuries to the spleen6,7.
To be considered for NOMSI the patient has to be hemodynamically stable. Patients who present with
transient hypotension but respond to a challenge of 2 litres of resuscitation fluid are considered
hemodynamically stable. Patients who remain unstable must be considered for immediate laparotomy
and the diagnosis of specific organ injury is not essential. A Focussed Ultrasound for Trauma (FAST)
or diagnostic peritoneal lavage (DPL) for detection of haemoperitoneum is the appropriate tool in this
setting8,9.
Patients who are hemodynamically stable need to be evaluated by abdominal CT scan. The grade of
injury to the spleen can be qualified on a CT scan, Table I.
Injuries to the spleen identified on the CT regardless of the severity of splenic trauma can be
managed non-operatively. Patients should be placed on strict bed rest. Serial abdominal examinations
are done to assess for signs of peritonitis and haemoglobin measurements are done every 6-8 hours.
The American Pediatrics Surgical Association (APSA) trauma committee proposes that admission to
the intensive care unit (ICU) be reserved for grade IV and V injuries only10. If the patients remain
hemodynamically stable and if there is no fall of haemoglobin patients of grade I and II injuries are
23
allowed to ambulate and perform light duties after 48 hours. They can be discharged after 5 days of
hospitalisation. Patients with grade III, IV and V injuries need monitoring for 5 days. A follow up CT
may be done at this stage though the APSA does not propose that. If at any stage the haemoglobin
drops and more than 2 units of blood are required, a repeat CT scan is done. If the splenic injury is
stable one must look for other sources of blood loss. If the injury grade has increased, the
haemoperitoneum is larger or there is active bleeding present a laparotomy is indicated.
Table I. American Association for the Surgery of Trauma (AAST) spleen injury scale (1994 version)
_________________________________________________________________________________
Grade Injury Description
I Hematoma Subcapsular, nonexpanding, <10% surface area
Laceration Capsular tear, nonbleeding, <1cm parenchymal
depth
II Hematoma Subcapsular, nonexpanding, 10-50% surface area;
Intraparenchymal, nonexpanding<5cm in diameter
Laceration Capsular tear, active bleeding; 1-3cm parenchymal
Depth not involving a trabecular vessel
III Hematoma Subcapsular, >50% surface area or expanding;
Ruptured subcapsular hematoma with active
Bleeding; intraparenchymal hematoma >5cm or
Expanding
Laceration >3cm parenchymal depth or involving trabecular
Vessels
IV Hematoma Ruptured intraparenchymal hematoma with
Active bleeding
Laceration Laceration involving segmental or hilar vessels
Producing major devascularization (>25% of spleen)
V Laceration Completely shattered spleen
Vascular Hilar vascular injury that devascularizes the spleen
In a retrospective review of 105 patients with blunt trauma to the spleen Velmahos et al6 observed
that 47% of the patients required emergent laparotomy while 53% could be managed by NOMSI
initially. Those who required urgent surgery had higher grades of splenic injuries. The NOMSI failed in
29 (52%) patients. Eighteen patients had to be operated in less than 24 hours while the remaining 11
patients required splenectomy between1-7 days after injury. When the variables were analysed by
stepwise logistic regression analysis, then transfusion of more than one unit of blood and CT splenic
injury grade of III or higher were found to be the two independent risk factors for the failure of NOMSI.
In a more recent review published in year 2006 Rajani et al11 performed a retrospective cohort
analysis of two consecutive 7.5 year time periods, 222 patients who were treated between 1991 and
1998 and the other group of 403 patients treated between 1998 and 2005. NOMSI could be
implemented in 57% of the initial cohort and 85% of the later cohort and the success of nonoperative
management increased from 77% to 96%. Interestingly 16% of the present cohort of patients had
immediate angiography and embolization done. Splenic artery embolization (SAE) improved splenic
salvage.
Angiographic embolization
The introduction of angiographic embolization (AE) has increased the success rate of NOMSI12,13,14.
Some of the centres have carried out the procedure on all grades of injuries while others have used it
on more severe injuries. In a recent study Gardner et al15 performed AE in all patients who had grade
3 to 5 injuries immediately or the next morning. This prospective group of 64 patients was compared
with a retrospective group of 69 patients managed previously when AE was not used. The success
rate of NOMSI increased from 79% to 96% in the group where AE was used. The long-term effect of
AE on splenic functions is, however, yet to be evaluated.
24
References
1. Pachter HL, Guth AA, Hotstetter SR, Spencer FC. Changing patterns in the management of splenic trauma: the
impact of nonoperative management. Ann Surg 1998; 227:708-719.
2. Morris DH, Bullock FD. The importance of spleen in resistance to infection. Ann Surg 1919; 70:513-21.
3. King H, Shumacker HB Jr. Susceptibility to infection after splenctomy performed in infancy. Ann Surg 1952;
136:239-242.
4. Diamond LK. Splenectomy in childhood and the hazard of overwhelming infection. Pediatrics 1969; 43:886-9.
5. Holdsworth RJ, Irwing AD, Cuschieri. Postsplectomy sepsis and its mortality rate:actual versus perceived risks.
Br. J. Surg.1991; 78:1031-1038.
6. Velmahos GC, Chan LS, Kamel E et al. Nonoperative management of splenic injuries, Have we gone too far? Arch
Surg 2000; 135:674-81.
7. Wasvary H, Howells G, Vilabha M et al. Nonoperative management of adult blunt splenic trauma:a 15 years
experience. Am Surg 1997; 63:694-99
8. Hoffmann R, Nerlich M, Muggia-Sullam M, et al. Blunt abdominal trauma in cases of multiple trauma evaluated by
ultrasonography: a prospective analysis of 291 patients. J Trauma 1992; 32:452-8.
9. McKenney M, Lentz K, Nunez D, et al. Can ultrasound replace diagnostic peritoneal levage in the assessment of
blunt trauma? J Trauma 1994; 37:439-41.
10. Stylianos S. Evidence-based guidelines for resource utilization in children with isolated spleen or liver injury. J
Ped Surg 2000; 35(2): 164-9.
11. Rajani RR, Claridge JA, and Yowler CJ, et al. Improved outcome of adult blunt splenic injury: a cohort analysis.
Surgery 2006; 140:625-32.
12. Davis KA, Fabian TC, Croce MA, et al. Improved success in nonoperative management of blunt splenic injuries:
embolization of splenic artery psedoaneurysm. J Trauma 1998; 44:11008-013.
13. Haan J, Scott J, Boyd-Kranis RL, et al. Admission angiography for blunt splenic injury: advantages and pitfalls. J
Trauma 2001; 51:1161-65.
14. Haan JM, Biffl W, Knudson MM et al. Splenic embolization revisited: a multicenter review. J Trauma 2004; 56:542-
47.
15. Gardner C, Dormagen JB, Eken T, et al. Nonoperative management of splenic injuries: improved results with
angioembolization. J Trauma 2006; 61:192-8.
25
Management of liver trauma
Dr.Sham Singla
Liver is the second most frequently injured organ in blunt abdominal trauma patients, but it is
commonest cause of death after abdominal injury. Being the largest solid abdominal organ with a
relatively fixed position, it is prone to injury. About 60% of all the blunt abdominal trauma, are caused
by automobile accidents. According to IRTE (Institute of Road Traffic Education) 9 people are killed &
39 injured every hour, over roads of India . Liver is the most common abdominal organ to be injured
by penetrating trauma, which may be caused by bullets, shrapnel, knives etc.
Large size, friable parenchyma, thin capsule & relatively fixed position in relation to the spine &
surrounded by rib cage, make the liver particularly prone to injury. Right lobe is more commonly
injured than left. Mostly it involves (>85% cases) segments VI, VII & VIII of the liver.
Incidence: US =15-20%
India = not known
Sex: Males are affected more.
Age: Though Adults are affected more, children are more susceptible because of pliable ribcage &
poorly developed liver (weaker connective tissue framework & hepatic veins lie in rigid canals &
contract poorly), and thus liver is incapable of achieving spontaneous haemostasis after injury.
Morbidity: Mild trauma (<25% of one lobe) = 3 months

Moderate trauma (25-50% of one lobe) = 6 months
Severe trauma (>50% or both lobes) = 9-15 months
Mortality: Fallen from >50% to 7-12% in good centres

Higher with blunt (>20%) than penetrating (1%) injuries
Higher with poly-trauma (nearly 70%) than liver alone (10%)
Mechanism of injury
Mechanisms of blunt liver trauma include, crushing and shearing forces. Rapid deceleration as in road
traffic accidents and falls from height, cause differential movement among adjacent structures. As a
result, shear forces are created and cause hollow, solid, visceral organs and vascular pedicles to tear,
especially at relatively fixed points of attachment. Youth have a better tolerance than old because of
more elastic tissues and firm abdominal muscles. The crushing forces are generated when intra-
abdominal contents are crushed between the anterior abdominal wall and the vertebral column or
posterior thoracic cage. The solid viscera (e.g. spleen, liver, kidneys) are especially vulnerable.
Liver injury scale (American Association for the Surgery of Trauma)
GRA
TYPE DESCRIPTION
DE
Hematoma Subcapsular, nonexpanding, <10% area capsular tear, no
I
Laceration bleeding, <1 cm deep
10-50% area nonexpanding, <10cm diameter, nonexpanding
II ---do---
intraparenchymal, 1-3 cm deep, <10 cm long
III ---do--- Expanding / ruptured, >50% area,>10 cm long >3 cm deep
Parenchymal disruption 25-75% of lobe, 1-3 Couinaud‘s
IV Laceration
segment in a lobe
Laceration/ 75% of lobe, >3 segment in a lobe, Juxtahepatic venous
V
Vascular injuries
VI Vascular Hepatic avulsion
Initial assessment & resuscitation:
26
Priorities in resuscitation and diagnosis are established, based on hemodynamic stability and the
degree of injury. The goal of the primary survey, as directed by the Advanced Trauma Life Support
protocol, is to identify and expeditiously treat life-threatening injuries. The protocol includes :
 Airway, with cervical spine precautions
 Breathing
 Circulation (target BP 100mm Hg)
 Disability
 Exposure
Investigative evaluation
Chest – Radiograph
Chest radiograph is an integral part of abdominal examination. It helps in predicting associated
injuries apart from raising suspicion for liver. In presence of shock resuscitation measures take
precedent over X-ray studies. When laparotomy is clearly indicated, the time is not wasted for X-rays.
 Pneumoperitoneum – Hollow viscera injury

 Raised left/right hemidiaphragm – Perisplenic/Hepatic hematoma
 Lower ribs fracture – Liver/Spleen injury
 Abdominal contents in the chest – Ruptured hemidiaphragm
Ultrasonography
Ultrasound examination is emerging as a fast and noninvasive diagnostic modality that is especially
applicable in blunt abdominal trauma. Focused assessment by sonography in trauma (FAST)
includes, study of the subhepatic space, the left subphrenic space (spleen), the suprapubic and pelvic
regions, and a subxiphoid view of the pericardium. FAST examination relies on haemoperitoneum to
identify patients with injury. The study is considered abnormal if fluid is detected. It can detect
hematomas and lacerations.
Abdominal Computerised Tomography
CT scan is the criterion standard, for the detection of solid organ injuries. It is the examination of
choice in stable patients. Its accuracy ranges from 92-98%. It is the most frequently used method to
evaluate a stable patient with abdominal trauma .Contraindications include clear indication for
exploratory laparotomy, hemodynamic instability, un-cooperative or irritable patient and allergy to
contrast media.
MRCP: for bile duct injuries
Angiography: to localize source of bleeding & to embolize
27
NON-OPERATIVE MANAGEMENT OF ABDOMINAL TRAUMA (NOMAT)
Eligibility criteria:
 Haemodynamic stability
 Awake, alert & responding
 Hollow viscera injury excluded
 No other indication for laparotomy
 No coagulation defect
CECT criteria for NOMAT:

 simple hepatic parenchymal laceration or hematoma
 absence of active haemorrhage
 haemoperitoneum of < 500 ml
 limited need for liver related blood transfusion
 absence of diffuse peritoneal signs in patients not neurologically impaired
 absence of other peritoneal injuries that would otherwise require an operation.
NOMAT consists of:

 Strict bed rest
 Nil per oral
 Nasogastric aspiration
 Broad spectrum antibiotics
 I/O, TPR & BP charting
NOMAT is abandoned in
 Deterioration of vital signs
 Signs of peritonitis
 Continued need for blood transfusions
 Falling haematocrit
NOMAT is successful in 80% of grade I—III injuries & some of grade IV---V injuries
Surgeon‘s monitoring is must for first 12-24 hrs
Hospitalization is must for at least 5 days or may be longer with high grade injuries
Follow up
Bed rest for 8 weeks in grade I---IV injuries (i.e. to avoid contact sports & heavy physical activities)
Repeat CECT is useless until a complication arise in grade I—III injuries
Follow up CECT is indicated in grade IV—VI injuries
Angiographic Embolization
To confirm source of slow, ongoing, active bleeding, preoperatively in stable patients even in early
postoperative period. It is indicated when there is a high-density dot, streaming of contrast media or
very high density of contrast media in area of injury. Percutaneous angiographic embolization is
becoming an established modality in primary treatment of liver trauma in some centres
Current treatment philosophy

In past, most injuries were treated surgically. However a review of surgical literature confirms that, as
many as 80% of adults & 97% of children are treated conservatively. In 86% of cases it has stopped
bleeding by the time surgical exploration is performed & 67% of the operations done are non-
therapeutic.
(1) hemodynamic stability rather than CECT findings determine which patient should be managed
conservatively
(2) in stable patients less treatment (conservative), is probably the best treatment
(3) more transfusion means more suspicion of grievous injury
(4) an interventional radiologist should be part of treating team
28
(5) if conservative treatment fails, abbreviated laparotomy & planned reoperation should be
considered at an early point
(6) most complications should be managed in a non-operative fashion, unless clear surgical
indications are present. However a small percentage of patients need operative management.
Operative Management
Indications
 Unstable patients
 Progressive peritonism
 Continuous bleeding & non-availability of angiography
 BT requirement exceeding 1500 ml / day {empiric judgement}
 Grade IV—VI injuries
 Late referral with pack in situ & without coagulopathy
 Other complications
Ideal conditions for Surgery
 Blood volume restored preoperatively

 Adequate amount of blood available beforehand
 Rapid infusion blood warmer
 Appropriate sutures opened ready
 Optimal lighting with a headlamp
 Surgeon‘s preparedness for grade IV—VI injuries
 Capability to terminate the operation abruptly & timely
Operative Strategy ----- No heroic surgery
 Incisions
o Upper midline vertical: Generally recommended
o From xiphoid process up to the umbilicus- Most rapid, bloodless & thorough
exploration can be done
o Right subcostal with thoracic extension
o Median sternotomy
o Lateral extension of right subcostal
o Midline incision preferred
 Rapid evacuation of hemoperitoneum
 Damage Control {Abbreviated} Laparotomy
 Initially focus only over major bleed
 No bleeding, no exploration
 If bleeding, compress for 20 min. by clock
 Still bleeding –inflow occlusion then intermittent release
Exploration
 Clots removed, inspect & palpate to identify the source of bleeding.
 Temporary control of bleeding, by use of packs & manual compression.
 Rapid inspection of remainder of abdomen for attention if required.
 Blood & clots removed by manual scooping & use of two suckers
 Each quadrant cleared & several laparotomy pads placed in the abdomen
 For proper visualization & bleeding control all ligamentous attachments divided. Hepatic vein
injury is suspected if injury is posterosuperiorly placed- then resist to pull the liver anteriorly &
to the left. This may cause torrential bleeding & a rapid death. Air embolism may occur.
29
Retrohepatic bleed is temporarily controlled by pressing the liver against posterior parieties.
Packing
Indications: When other surgical methods fail
Arterial PH<= 7.2
Body temperature<= 32degrees centigrade
Anticipation of >= 10 units BT requirement
Non-expertise in hepatic injuries
Uncontrollable coagulopathy --- an absolute indication
Bilobar injury
Large nonexpanding hematoma & capsular avulsion
Suspected injury to the vena cava or hepatic veins
Always start packing from behind the liver in both the right & the left paravertebral space, to avoid the
IVC compression. After packing each quadrant, packs removed sequentially to identify source of
bleeding. Right upper quadrant packs are to be removed last. No bleeding, no packing. Don‘t disturb
silent wound. Don‘t inspect depth of the wound. Nonexpanding retrohepatic hematoma {<5 cm} is not
to be opened up. Always pack above & below the liver & never into the fracture. Pack is to compress
rather than to place in depth of the wound. Pack can be a roll gauze or laparotomy pad. Pack can be
kept for 72 hrs, & removed very gently with 10 ml H2O2 in 500 ml NS.
Haemostasis
Hand Pressure
A temporary method
Gentle but firm pressure applied to approximate the edges
Pringle Manoeuvre
For brisk haemorrhage
To exclude arterial component
Structures in porta hepatis compressed with left thumb on hepatoduodenal ligament anteriorly
and middle & index finger into foramen of Winslow posteriorly
Non-crushing vascular clamp
For inflow occlusion
For intermittent clamping
Just to compress vessels in porta hepatic
Not to injure CBD
Duration from 20 min up to 1 hr at a stretch
Topical haemostatic agents
Fibrin Glue
 A combination of fibrinogen, thrombin & calcium chloride
 Very effective in controlling oozing from raw liver surface
 Accelerates wound healing, inhibits bacterial growth and reduces bleeding & bile leak
 Disadvantage is hypotension & theoretical risk of viral transmission (hepatitis, HIV)
Liver sutures (Hepatorrhaphy)
 A heavy absorbable suture on large curved blunt tipped needle

 Passed deeply into the substance, in figure of 8 suture or simple suture
 May be tied over absorbable bolsters
 Should go beyond depth of the wound, but avoid central structures
 Should be passed several centimeters away from the fracture itself
 Should be tied tightly enough to oppose the edges, but not so tight so as to tear or strangulate
the tissue. It could be life saving and extraordinarily effective.
30
Balloon Tamponade
In high velocity wounds & stab injuries Foleys catheter, Penrose drain (gunshot wounds), Sengstaken
Blakemore tube can be used for intrahepatic hematomas to produce tamponade effect. They are
slowly deflated & gradually withdrawn after 72 hrs.
Mesh
Absorbable material, wrapped around liver

 Two sheets of synthetic absorbable mesh are sutured together, either on two adjacent sides
to create a ―pitta pocket‖, or longitudinally to wrap the liver in a ―cigarette roll‖, and secured
anteriorly and posteriorly
 Cholecystectomy should be done if right lobe is wrapped, (to avoid necrosis).
 For major parenchymal disruption i.e. grade III—IV lacerations
 For tamponading large intrahepatic hematomas thus minimizing risk of delayed rupture
 For compression effect
 Not indicated for juxta-caval or hepatic vein injury
 Not very successful because it is time consuming
Omental packing
Can be placed in depth of the wound to stop oozing from the low-pressure venous system to fill any
dead space
Extraparenchymal hepatic artery ligation
Rarely done today
Can lead to gangrenous cholecystitis
Intrahepatic tamponade with penrose drain
In low velocity gunshot wounds & stab injuries
Exploration of the wound
Not recommended generally, done in brisk, active, massive haemorrhage
Finger fracture technique ---- to explore the depth of the wound & to see the bleeding source
Hepatotomy with direct suture ligation
For severe parenchymal injuries
Extend liver laceration by finger fracture technique, electrocautery or an ultrasonic dissector, to
expose damage of vessels & hepatic ducts which can then be ligated, clipped or repaired under direct
vision
Needs further evaluation
Repair of retrohepatic vascular injuries
A vascular clamp {Satinsky clamp} applied to the IVC, posterior to ostium of hepatic vein, digital
pressure / sponge stick pressure given for small injuries & rapid repair by vascular sutures
1. Total vascular isolation of liver for major bleed ---- hepatic vein or retrohepatic IVC injury. It
involves clamping of the porta & infrahepatic & suprahepatic vena cava in chest and
clamping of infradiaphragmatic aorta
2. Venovenous bypass
Insertion of shunt from left common femoral vein to left axillary vein
Portal vein and hepatic artery occlusion and clamping of supra and infrahepatic
vena cava
3. Atriocaval shunting
4. Non shunting approach
Mortality uniformly high (>50%)

Most serious unresolved problem in liver trauma
31
Debridement
Devitalized tissue should be removed as complications are more
Done along the line of fracture
Hilar dissection not advocated
Hepatic veins rapidly ligated because of air embolism
Called as resectional debridement as it is nonanatomical
Mostly done for right lobe
Region of middle hepatic vein should ideally be preserved to assure drainage of segment IV,
V &VII
Drainage
By closed suction drain to monitor bile & blood
For grade III or higher injuries
Complications
 Haemorrhage
 Hypothermia
 Hypocalcemia
 Acidosis
 Consumptive coagulopathy, DIC
 Sepsis
 Biliary fistula
 Biloma
 Ductal stricture
 Bilhemia
Further reading
1. Carrillo EH, Wohltmann C, Richardson JD, Polk HC Jr: Evolution in the treatment of complex blunt liver injuries.
Curr Probl Surg 2001 Jan; 38(1): 1-60[Medline] .
2. Casillas VJ, Amendola MA, Gascue A, et al: Imaging of nontraumatic hemorrhagic hepatic lesions. Radiographics
2000 Mar-Apr; 20(2): 367-78[Medline] .
3. Fang JF, Chen RJ, Wong YC, et al: Classification and treatment of pooling of contrast material on computed
tomographic scan of blunt hepatic trauma. J Trauma 2000 Dec; 49(6): 1083-8[ Medline] .
4. Fulcher AS, Turner MA, Yelon JA, et al: Magnetic resonance cholangiopancreatography (MRCP) in the
assessment of pancreatic duct trauma and its sequelae: preliminary findings. J Trauma 2000 Jun; 48(6): 1001-
7[Medline] .
5. Harper HC III, Maull KI: Transcatheter arterial embolization in blunt hepatic trauma. South Med J 2000 Jul; 93(7):
663-5[Medline] .
6. Jennings GR, Poole GV, Yates NL, et al: Has nonoperative management of solid visceral injuries adversely
affected resident operative experience? Am Surg 2001 Jun; 67(6): 597-600[Medline] .
7. Kirby RM, Braithwaite M: Management of liver trauma. Br J Surg 2000 Dec; 87(12): 1732[Medline] .
8. Knudson MM, Maull KI: Nonoperative management of solid organ injuries. Past, present, and future. Surg Clin
North Am 1999 Dec; 79(6): 1357-71[Medline] .
9. Leone RJ Jr, Hammond JS: Nonoperative management of pediatric blunt hepatic trauma. Am Surg 2001 Feb;
67(2): 138-42[Medline] .
10. Ma OJ, Kefer MP: Ultrasound detection of free intraperitoneal fluid associated with hepatic and splenic injuries.
South Med J 2001 Jan; 94(1): 54-7[Medline] .
11. McGehee M, Kier R, Cohn SM, McCarthy SM: Comparison of MRI with postcontrast CT for the evaluation of acute
abdominal trauma. J Comput Assist Tomogr 1993 May-Jun; 17(3): 410-3[Medline] .
12. Mirvis SE, Whitley NO, Gens DR: Blunt splenic trauma in adults: CT-based classification and correlation with
prognosis and treatment. Radiology 1989 Apr; 171(1): 33-9[Medline] .
13. Nehoda H, Hochleitner BW, Hourmont K, et al: Central liver hematomas caused by mountain-bike crashes. Injury
2001 May; 32(4): 285-7[Medline] .
14. Parks RW, Chrysos E, Diamond T: Management of liver trauma. Br J Surg 1999 Sep; 86(9): 1121-35[Medline] .
15. Poletti PA, Mirvis SE, Shanmuganathan K, et al: CT criteria for management of blunt liver trauma: correlation with
angiographic and surgical findings. Radiology 2000 Aug; 216(2): 418-27[Medline] .
16. Richards JR, McGahan JP, Pali MJ, Bohnen PA: Sonographic detection of blunt hepatic trauma: hemoperitoneum
and parenchymal patterns of injury. J Trauma 1999 Dec; 47(6): 1092-7[Medline] .
17. Sondenaa K, Horn A, Nedrebo T: Diagnosis of blunt trauma to the gallbladder and bile ducts. Eur J Surg 2000
Nov; 166(11): 903-7[Medline] .
32
18. Udobi KF, Rodriguez A, Chiu WC, Scalea TM: Role of ultrasonography in penetrating abdominal trauma: a
prospective clinical study. J Trauma 2001 Mar; 50(3): 475-9[Medline] .
19. Yamamoto F, Pu Y, Igimi H, et al: MR imaging of traumatic hepatic laceration: evaluation and course of healing
after surgery. Abdom Imaging 1993; 18(3): 253-7[Medline] .
33
Tissue biopsy: a surgeon‘s viewpoint
Biopsy is a medical diagnostic test used to determine the structure and composition of tissue or cells.
Biopsy involves sampling cells or living tissue from an organ or other part of the body. In order to
make a diagnosis, examination of the tissue sample is then performed using a microscope. Most
biopsy procedures are minor, do not require sedation, and many require no anaesthesia or only local
anaesthesia. Biopsy is derived from the Greek roots "bio" and "opsis". Thus "biopsy" may be loosely
translated to "view of the living" or "appearance of life."
Biopsy is a definitive way to test for the presence of a malignant tumor or to confirm if an abnormality
is benign (not cancerous). If cancer is present, a pathologist can study the biopsy specimen to help
determine what type of cancer exists and to grade the tumor by determining whether the cancer cells
are likely to grow or spread slowly or quickly.
Why is Biopsy Performed?
Lesions needing biopsy are usually discovered either because they can be felt by a patient or
physician or they are visible on a medical imaging examination such as X-ray, Ultrasound, CT
scan, MR exam, etc. Screening tests such as Pap smear or PSA blood test (prostate specific
antigen) can also detect otherwise unknown cancer and lead to biopsy of the appropriate site.
Once an abnormality is found, biopsy is often then used to determine the exact nature of the
suspected abnormality. A physician may perform a biopsy as part of cancer diagnosis, in order to
determine whether an area of concern is malignant (cancerous) or benign (not cancerous). For
example, breast biopsy is the removal of a sample of breast tissue for laboratory (histologic)
examination by a pathologist and is the definitive way to determine if an abnormality is cancerous or
not. A clinical pathologist is a specially trained physician who performs laboratory analysis of the
biopsy specimen (tissue sample) to determine its type.
Microscopic examination of tissue (histology) or cells (cytology) usually gives a correct and definitive
diagnosis. In the case of a malignant tumor, biopsies of the surrounding tissue and the lymph nodes
can be done to determine whether the cancer has spread (metastasized). In the case of cancer
diagnosis, biopsy can also allow the physician to grade the cancer. Another important use of biopsy
is to determine the cause of infections or inflammations that can not be explained with other testing.
Surgical biopsy (excisional biopsy) may involve removing the entire mass (tumor) for testing. Biopsy is
often done using the guidance of imaging or endoscopy. If cancer is present, a pathologist can usually
tell what type of cancer it is and may be able to judge whether the cells are likely to grow slowly or
quickly. Click here to go to the section on types of biopsy .
Percutaneous biopsy is routinely done using the guidance of medical imaging (such as ultrasound,
mammography or CT imaging). The primary physician, radiologist, surgeon or other physician will
determine the most appropriate method of biopsy and guidance based on various factors including:
 the tissue, organ or body part to be sampled
 how suspicious the abnormality appears
 the size, shape and other characteristics of the abnormality
 the location of the abnormality
 the number of abnormalities
 other medical conditions a patient may have
 the preference of the patient, and
 the systems available at a given hospital or healthcare location
Biopsy is often performed to diagnose diseases and lesions of various organs including:
 Bone biopsy is performed for people with bone pain and other indicators of bone cancer.
 Bone marrow biopsy is performed in cases of abnormal blood counts, such as unexplained
anemia, high white cell count, and low platelet count. In adults, the sample is usually taken
from the pelvic bone.
 Breast biopsy is performed to confirm if a lesion is benign or malignant
 Cervical biopsy is often performed endoscopically to diagnose cervical cancer or other
cervical diseases. Methods of cervical biopsy include the cervical punch and cone biopsy.
34
 Joint biopsy is usually guided by arthroscopy. A tissue specimen is taken from the synovial
membrane that lines the joint. Joint biopsy can diagnose gout, pseudogout, bacterial
infections, lupus, rheumatoid arthritis or Reiter's disease.
 Kidney biopsy can be performed to diagnose a long list of disorders. When renal function is
diminished by an unknown cause or when imaging exams such as CT , Ultrasound, Nuclear,
or MRI show abnormalities but cannot differentiate between some of the possible causes.
 Liver biopsy may help identify liver disorders and diagnose abnormalities as benign or
malignant.
 Lymph node biopsy can be done to look for diseases such as chronic lymphatic leukemia,
Hodgkin's disease, infectious mononucleosis, and rheumatoid arthritis. Lymph node biopsy
can also diagnose if cancer has spread from the primary location into the lymphatic system.
This can help the physician determine the stage of cancer.
 Lung biopsy is performed to confirm diagnosis of widespread lung disease and to diagnose
abnormalities. Lung biopsy is done to confirm cancer or other lung disease. Lung biopsy can
also examine tissue from the trachea (wind pipe) and bronchi (major air passages of the
lungs).
 Pleural biopsy is sampling of the pleura, the sac that covers the lungs. Pleural biopsy is done
to differentiate between malignant and non-malignant disease and to diagnose viral, fungal, or
parasitic disease and collagen vascular disease of the pleura.
 Prostate biopsy is done to confirm or rule our prostate cancer or to determine the cause of
prostate enlargement or elevated serum prostate markers (PSA: prostate specific antigen).
 Small Intestine biopsy is often performed to determine what may be causing diarrhea or poor
absorption in the intestine.
 Skin biopsy is often done to test for malignant cancer and to diagnose chronic bacterial or
fungal skin infections.
 Synovial biopsy is a type of endoscopic biopsy used to sample synovial tissue from the
surface of a joint.
 Thyroid and parathyroid biopsy is done to diagnose people with thyroid enlargement or
nodules, breathing and swallowing difficulties, vocal cord paralysis and other problems such
as unexplainable weight loss. Thyroid biopsy may be used to diagnose Hashimoto's disease,
hyperthyroidism, and nontoxic nodular goiter.
Biopsy may also be performed to sample the following organs to test for cancer and other disease:
adrenal gland, biliary tract, bladder, carpal tunnel, colon, endometrium, gingiva (gums), heart, muscle,
nerve, salivary gland, small bowel, mouth, nasal mucosa, rectum, testicle, throat, and tongue.
Types of Biopsy
Many types of biopsy exist.

 Aspiration or FNA Biopsy
 Cone Biopsy
 Core Needle Biopsy
 Suction Assisted Core Biopsy
 Endoscopic Biopsy
 Punch Biopsy
 Surface Biopsy
 Surgical Biopsy (or Excisional Biopsy)
The primary physician, radiologist, surgeon or other physician will determine the most appropriate
method of biopsy and guidance based on various factors including:
 the tissue, organ or body part to be sampled
 how suspicious the abnormality appears
 the size, shape and other characteristics of the abnormality
 the location of the abnormality
 the number of abnormalities
 other medical conditions a patient may have
 the preference of the patient, and
 the imaging and biopsy systems available at a given hospital or healthcare location
35
Biopsies are usually guided by the method that identifies the abnormality best. Palpable lumps can be
felt and therefore no additional guidance is needed in most cases. Lesions discovered by an imaging
test, for example, mammography or CT, will often need biopsy that is guided by the modality that
shows the lesion the best. For example, CT is usually the method of choice for imaging the lungs, so
CT imaging is used to guide most lung biopsies. If an abnormality is seen well on multiple imaging
tests, the modality that provides the safest, most accurate, fastest and/or least expensive route will be
used to guide the biopsy. Lesions discovered by a screening test such as PSA may require blind
sampling biopsy since there is often no focal visible or palpable abnormality to target.
Aspiration or FNA Biopsy is performed with a fine needle attached to a syringe. Aspiration biopsy is
often referred to as Fine Needle Aspiration (FNA). FNA biopsy is a percutaneous (through the skin)
biopsy. FNA biopsy is typically accomplished with a fine gauge needle (22 gauge or 25 gauge). The
FNA procedure is often performed, for example, to diagnose nonpalpable breast abnormalities The
area is first cleansed and then usually numbed with a local anesthetic. The needle is placed into the
region of the abnormality such as a cyst or tumor. Once the needle is placed, a vacuum is created
with the syringe and multiple in and out needle motions are performed. The cells to be sampled are
sucked into the syringe through the fine needle. Three or four samples are usually taken.
Before microscopic examination is made, the sample of fluid and cells is sometimes spun at high
speed in a centrifuge (a device for separating substances in a liquid by spinning the mixture at high
speeds) then a small amount is placed on a slide and covered with a plastic slip. A smear is prepared
by spreading samples of fluid and cells onto glass slides. The specimens are then fixed (preserved)
and stained to improve viewing. The preservation (fixing) is often performed by heating the slide with
a Bunsen burner or by using a methanol solution. A cytologist (pathologist who examines cells) then
uses a microscope to examine individual cells for abnormalities, paying particular attention to the size,
shape and structure of the cell and cell nucleus.
Tumors of deep, hard-to-get-to structures such as the pancreas, lung, and liver are good candidates
for FNA. Such FNA procedures are typically done by a radiologist under guidance by ultrasound or
computed tomography (CT) imaging and usually require no anesthesia or only local anesthesia.
Thyroid abnormalities are also excellent candidates for FNA.
Cone Biopsy removes a piece of tissue which is cylindrical or cone shaped. Cone biopsy is
performed to diagnose cervical cancer. Cone biopsy is often done following a pap smear, colposcopy
(examination of the cervix under illuminated magnification), and a punch biopsy.
After the tissue is removed, it is analyzed in the pathology laboratory to determine whether cancer is
present. Cone biopsy may also be performed as a treatment if a cancer is small enough to be
completely removed during biopsy. There are two main methods used to perform cone biopsy. The
LEEP (also called LLETZ) method, short for loop electrosurgical excision procedure, removes the
tissue by using a wire that is heated by an electrical current. Patients are given local anesthesia and
the procedure can be performed quickly in a physician's office. Another method of cone biopsy
involves using a surgical scalpel or laser to remove the tissue. This procedure typically requires
general anesthesia and may be performed in a hospital or outpatient facility. However, an overnight
hospital stay is not usually required.
The most common side effects of cone biopsy include cramping/discomfort and moderate or mild
bleeding for a few weeks after the procedure. Patients should avoid sexual intercourse, tampons, and
douching until the incision is completely healed, which may take several weeks. Patients should also
discuss other possible side effects of cone biopsy prior to the procedure.
The advantages of cone biopsy are that it provides a large sample of tissue for analysis and it can
sometimes completely remove the cancer so the patient does not need additional surgery. However,
because complications from cone biopsy are possible, women should discuss all aspects of the
procedure with their physician before undergoing biopsy. If a cone biopsy is recommended after
abnormal Pap smear results, a patient may wish to ask if a colposcopy (looking at the cervix with
magnification) or cervical biopsy would be an appropriate alternative for her (if they have not already
been performed), based on her individual case.
Core Needle Biopsy (or core biopsy) is performed by inserting a small hollow needle through the skin
and into the organ or abnormality to be investigated. The needle is then advanced within the cell
36
layers to remove a sample or core. Needle biopsy is also a type of percutaneous (through the skin)
biopsy. The needle may be designed with a cutting tip to help remove the sample of tissue. Core
biopsy is often performed with the use of spring loaded gun to help remove the tissue sample.
Core biopsy is typically performed under image guidance such as CT imaging, ultrasound or
mammography. The needle is either placed by hand or with the assistance of a sampling device.
Multiple insertions are often made to obtain sufficient tissue, usually multiple samples are taken.
Patients may experience a slight pressure, but usually do not experience significant pain. As tissue
samples are taken, a click may be heard from the sampling instrument. The core tissue samples will
be sent to the pathology laboratory for diagnosis. In some cases, the pathologist can attend the
biopsy to examine imprints of the samples with a microscope. This can allows the pathologist to
determine the adequacy of the sample and perhaps offer preliminary results.
Vacuum Assisted Biopsy: Core biopsy is sometimes suction assisted with a vacuum device. This
method enables to removal of multiple samples with only one needle insertion. Vacuum assisted core
biopsy is being used more and more in breast biopsy procedures and is guided via stereotactic
mammography or ultrasound imaging. However, unlike core biopsy, the vacuum assisted biopsy
probe is inserted just once into the tissue through a tiny skin nick. Multiple samples are then taken
using a rotation of the sampling needle aperture (opening) and with the assistance of suction.
Endoscopic Biopsy is a very common type of biopsy. Endoscopic biopsy is done through an
endoscope (a fiber optic cable for viewing inside the body) which is inserted into the body along with
sampling instruments. The endoscope allows the physician to visualize the abnormality and guide the
sampling. Endoscopic biopsy may be performed of the gastrointestinal tract (alimentary tract
endoscopy), urinary bladder (cystoscopy), abdominal cavity (laparoscopy), joint cavity (arthroscopy),
mid-portion of the chest (mediastinoscopy), or trachea and bronchial system (laryngoscopy and
bronchoscopy), either through a natural body orifice or a small surgical incision. The endoscopist can
directly visualize an abnormal area on the lining of the organ in question and pinch off tiny bits of
tissue with forceps attached to a long cable that runs inside the endoscope.
Punch Biopsy is typically used by dermatologists to sample skin rashes, moles and other small
masses. After a local anesthetic is injected, a biopsy punch, which is similar in function to a small (3
mm to 4 mm or 0.15 inch in diameter) version of a cookie cutter, is used to cut out a cylindrical piece
of skin. The opening is typically closed with a suture (small stitches) and heals with minimal scarring.
Punch biopsy may also be performed when removing small tissue samples from the cervix.
Surface Biopsy involves sampling or scraping the surface of a sore or tumor to remove cells for
pathologic testing. Surface biopsy is often performed by dermatologists to remove a small piece of
skin to test for carcinoma (cancerous tissue).
Surgical Biopsy (or Excisional Biopsy): surgical biopsy can be excisional (removal of an entire
lesion) or incisional (removal of a piece of a lesion). Until about a decade ago, most biopsies
performed were open surgical procedures. However, surgical biopsy is less common now. Surgical
biopsies can be performed on abnormalities that can be seen or felt by the surgeon or pre-operative
imaging can help provide a road map to the lesion. In cases of non-palpable breast lesions, a
percutaneous wire can be placed in or near the lesion using mammogram or ultrasound for guidance.
This marker wire provides a target for the surgeon. The removed tissue is then histologically analyzed
by a pathologist (a special laboratory physician uses microscopic analysis of the tissue to determine
its type).
Some types of tumors (such as lymphoma, a cancer of the lymphocyte blood cells) need to be
examined whole to allow an accurate diagnosis. Thus enlarged lymph nodes are good candidates for
excisional biopsy.
Surgical biopsy has some disadvantages versus percutaneous needle biopsy. Surgical biopsies
require sutures (stitches) and can leave a disfiguring scar, they carry a small risk of mortality (due to
risks of anesthesia) and moderate chances of bleeding, infection, wound healing problems and even
fracture or migration of the localizing wire. Surgical biopsy usually requires one day of recuperation at
home and usually is significantly more expensive than the alternative methods. Advantages of
surgical biopsy include the ability to usually obtain a larger sample or complete removal of a lesion
37
versus percutaneous methods. Bleeding encountered during a surgical procedure is easier to control
than with percutaneous methods.
Image Guided Biopsy
Many percutaneous biopsy procedures are performed with the help of some form of image guidance.
Image guidance typically includes ultrasound and computed tomography (CT). Many breast biopsies
are performed under guidance of stereotactic mammography.
Computed tomography (CT) scanning is being used more and more to guide biopsy of lung and liver
lesions. Newer spiral or helical CT scanners are being equipped with so called "Interventional CT" or
"Fluoro CT" packages to allow real time CT imaging for the guidance of biopsy. Interventional CT
packages allow the radiologist to observe the biopsy needle in real time as it approaches and reaches
the target lesion within the patient‘s body. This significantly shortens procedure times and increases
diagnostic accuracy.
Ultrasound is also being used extensively to guide biopsy of the breasts and abdomen. Ultrasound
allows great flexibility for following the path of the needle to the lesion to be sampled. Ultrasound also
provides real-time display of the images as they are acquired. Ultrasound does not use x-rays and
can provide additional flexibility to the radiologist or other physician since essentially unlimited
imaging can be performed. The radiologist will determine if the abnormality can be seen well enough
on the ultrasound to enable guidance. In some cases, ultrasound can show that a breast lump is a
cyst (benign pocket of fluid), thus avoiding the need to perform a biopsy.
Stereotactic mammography is often used to guide breast biopsy using either the prone stereotactic
mammography or upright stereotactic mammography technique. "Stereotactic" means that the breast
biopsy path is imaged from two slightly angled directions to help guide the needle. Several
stereotactic pairs of x-ray images are made. Small samples of tissue are then removed from the
breast using a hollow needle that is precisely guided to the correct location via x-ray imaging and
computer coordinates.
Magnetic Resonance (MR) Imaging is being used at various locations to guide biopsy. New open MR
and "short bore" MR systems allow much greater access to the patient during scanning. This has
enabled the development of techniques and tools to allow MR guided biopsy. MR can provide images
in real-time which helps guide the trajectory of the needle as it approaches the target lesion. MR
provides high contrast resolution which allows radiologists to differentiate between organ structures
and abnormalities. Although use of MR guided biopsy is not yet widespread like CT or ultrasound
guided biopsy, over time, MR imaging will be used by more and more hospitals and diagnostic centers
to guide biopsy.
Patient Preparation and What To Expect During Percutaneous Needle Biopsy
There are three main types of percutaneous (through the skin) needle biopsy: fine needle
aspiration/FNA, core biopsy, suction assisted biopsy. Percutaneous biopsy is minimally invasive,
causes little pain and requires no sutures (stitches). Many percutaneous needle biopsy procedures
are performed with image guidance. Patients undergo percutaneous biopsy procedures while awake.
Many patients resume their normal lifestyle and routine the same day of the procedure.
Patient Preparation for a Percutaneous Biopsy
always check with the staff or physician performing the biopsy for specific directions, as procedures
vary. In general, patients may eat a light breakfast prior to the exam and biopsy procedure. A
comfortable two piece garment should be worn so that only one piece of clothing has to be removed.
Many times patients will be requested to wear a modest gown during the biopsy procedure. Women
who are scheduled for mammography and biopsy should not wear talcum powder, deodorant, lotion
or perfume under their arms or on their breasts on the day of the exam. Patients who take blood
thinners and aspirin are often asked to discontinue using them prior to the exam (3 days for Coumadin
or other blood thinners, 7 days for aspirin or ibuprofen). Any jewellery worn (especially earrings or
necklaces) should be easily and quickly removable, especially if the patient will undergo a prone (lying
face down) procedure.
38
What to Expect During a Percutaneous Biopsy
The skin above the region to be biopsied is cleansed. In some cases, the region of the biopsy needle
insertion will be anesthetized with a small hypodermic needle before the sampling needle is placed. In
addition, a general sedative is sometimes used to further reduce discomfort.
During the needle biopsy, patients may experience a slight pressure but should not experience any
pain. Typically, several samples are removed. The samples will be sent to the pathology laboratory for
diagnosis. The length of the exam can vary up to an hour, depending on the type of biopsy being
performed. During the procedure, the patient will be informed of what is occurring and what he or she
will need to do to assist in the exam. Typically the patient needs to cooperate and remain still. For
biopsy of the lung or upper abdomen or liver, patients may be required to hold their breath during the
imaging portion of the biopsy and during the needle placement. There will be some minor bleeding
when the needle is placed. For biopsy that involves passing the needle near a rib, patient discomfort
may be greater because of the sensitivity of the rib bone. This should not be cause for alarm. In
general, patients should try to relax and remain calm and still during a biopsy.
What to Expect After Percutaneous Biopsy
After the biopsy procedure, a bandage will be placed over the needle insertion area and a cold pack
may be applied to relieve swelling or bruising if needed. Typically, patients may take Tylenol (two 500
mg tablets) every four to six hours for discomfort, if needed. Patients should monitor the biopsy
location for signs of inflammation, bleeding or pressure. Patients should keep the biopsy site clean
and disinfected. Patients may notice some bruising of the area that should resolve in 5-7 days (or
possibly longer if initial bleeding was greater than usual). Patients should contact their physician if
they experience any excessive swelling, bleeding, drainage, redness, or heat in the area of the biopsy
or breast. Patients should discuss the final results of the biopsy procedure with their physician within a
few days of the procedure.
Risks of Biopsy
Needle biopsy is minimally invasive and is typically a very safe procedure. The benefits of
percutaneous biopsy often far outweigh the risks. However, as with all invasive procedures, certain
risks do exist. Depending upon the site being biopsied and the type of biopsy being performed, risks
can include:
 Infection of the biopsy area
 Hematoma: (blood blister) pooling of blood trapped inside the biopsy area
 Hemorrhage: bleeding
 Vasovagal response: loss of consciousness due to sudden slowing of the heart beat, usually
brought on by pain, stress, shock or fear)
 Rarely more significant complications can occur when structures near the biopsy target are
entered with the needle (for example, puncture of lung or bowel)
Surgical biopsy has some additional risks versus needle biopsy:

 Surgical biopsies require sutures (stitches) and can leave a disfiguring scar, depending on the
size of the excision
 Surgical biopsy carries a small risk of mortality (due to risks of anesthesia)
 Surgical biopsy causes moderate chances of bleeding, infection, wound healing problems
 The localizing wire may fracture or migrate during wire localization breast biopsy
 Surgical biopsy usually requires one day of recuperation at home
Biopsy Results
A "negative" biopsy means that no abnormal cells were present in the examined tissue or cell sample.
A "positive biopsy" means that abnormal cells are present in the examined tissue or cell sample.
Abnormal results are helpful in identifying:
 infectious processes: the infectious agent may be seen, or changes to the cells which are
caused (characteristic) of certain infection or disease may indicate the infectious agent is
present
39
 benign (non-cancerous) conditions: some characteristic cell changes may be present,
indicating the presence of a benign growth or process.
 Malignant: abnormal cells representing cancer. The pathologist can usually determine the
organ of origin of the cancer cells and therefore can often determine whether a tumor is
primary (from the organ being biopsied) or metastatic (tumor has spread to the organ being
biopsied)
This article can be found at: http://www.imaginis.com/biopsy/biopsy_performs.asp
Recommendations for gastrointestinal tissue biopsy

Histopathologic evaluation is helpful to differentiate malignant, inflammatory, and infectious
processes. Tissue biopsy specimens are routinely obtained from any suspicious lesion during
endoscopic evaluation. When the gross endoscopic appearance is normal, histologic analysis may
still provide useful information. Tissue analysis is occasionally performed to document the outcome of
prior endoscopic or medical therapy. When the gross endoscopic appearance reveals a specific
condition, tissue analysis is unnecessary if therapy will not be altered. Tissue biopsy should be
avoided when there is an increased potential for hemorrhage such as in patients with coagulopathies.
Techniques
Numerous techniques and devices have been designed to obtain adequate tissue samples. Pinch
biopsy is done with biopsy forceps and is the most commonly used form of tissue sampling. Multiple
biopsies improve the diagnostic yield; the size, location, specimen orientation, fixation, and staining
are also important. Pinch biopsy forceps usually obtain mucosal specimens. Occasionally, jumbo
biopsy forceps may also reach the submucosa. However, these forceps require a biopsy channel of at
least 3.6 mm and yield 2 to 3 times the surface area but are not generally deeper specimens. Brush
cytology may be a useful adjunct to pinch biopsy and helpful in the diagnosis of certain malignancies
and infections. Snare excision is used for removal of large polyps. A combination of techniques can
increase diagnostic accuracy. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is
capable of sampling subepithelial lesions and those extrinsic to the gastrointestinal (GI) tract such as
lymph nodes and pancreatic masses and is more fully discussed in the American Society for
Gastrointestinal Endoscopy (ASGE) Status Evaluation Report "Tissue Sampling During
Endosonography."
Esophagus
Malignant tumors of the esophagus can be diagnosed by biopsy alone in 95% of cases, except when
obstruction prevents adequate visualization and biopsy of the lesion. Eight to 10 biopsy specimens
should be obtained. The addition of brush cytology may increase the diagnostic yield. The most
common inflammatory condition, reflux esophagitis, occurs in patients with gastroesophageal reflux
disease (GERD). Endoscopy with tissue analysis is indicated to evaluate for the presence of Barrett's
esophagus or to rule out infection or malignancy masquerading as gastroesophageal reflux disease.
Erosive changes seen on endoscopy correlate well with histology, but isolated erythema is an
unreliable criterion for esophagitis. Conversely, abnormal histology (inflammatory cell infiltration with
polymorphonuclear cells or eosinophils) may be found by biopsy in patients with reflux symptoms who
have normal-appearing esophageal mucosa. Biopsy and cytology specimens of abnormal-appearing
mucosa may be needed to exclude malignancy, infectious esophagitis, certain autoimmune disorders,
and to detect Barrett's esophagus.
Barrett's esophagus is a condition in which the normal squamous mucosa is replaced by metaplastic
specialized intestinal epithelium and requires endoscopic biopsy for diagnosis. Patients with Barrett's
esophagus are at increased risk for esophageal adenocarcinoma, and their identification allows for
inclusion in surveillance programs. Histopathology reveals columnar epithelium without a brush border
and is distinguished from gastric mucosa by the identification of goblet cells, which may be aided by
the use of special stains (alcian blue). Severe ulcerative esophagitis may obscure underlying Barrett's
40
mucosa, and inflammation-induced atypia may be confused with dysplasia. In these instances,
aggressive medical therapy to heal esophagitis clarifies subsequent histopathologic interpretation.
Biopsies are also performed to detect dysplasia or adenocarcinoma. If dysplasia is known or

suspected to be present, then 4-quadrant biopsies at 1- to 2-cm intervals with additional specimens
from any mucosal abnormalities should be taken. A 2-cm protocol missed 50% of cancers in patients
with high-grade dysplasia, which were detected in a 1-cm protocol. Although large-capacity "jumbo"
forceps have been advocated, a retrospective study found that 4-quadrant biopsies every 2 cm
missed the same proportion of cancers when done with large-capacity (4/12, 33%) or standard-sized
(6/16, 38%) forceps. The turn-and-suction technique is advocated, in which the open forceps is drawn
close to the endoscope's tip, the scope turned toward the wall, suction applied, the forceps advanced,
closed, and the specimen obtained. For patients with high-grade dysplasia who opt against
esophagectomy, this technique performed at 3- to 6-month intervals has been reported to accurately
detect carcinoma, 96% of which were confined to the mucosa.
High-resolution magnifying endoscopy and chromoendoscopy with methylene blue has been
advocated to increase the detection of short-segment Barrett's esophagus by directing biopsy
location. Chromoendoscopy with Lugol's solution and methylene blue has been reported to increase
the detection of squamous cell carcinoma and neoplastic areas within Barrett's esophagus,
respectively, although the value of methylene blue in the surveillance of Barrett's esophagus has been
questioned. Analyzing the biopsy specimens with flow cytometry and DNA analysis may identify
patients with aneuploidy, polyploidy or 17p (p53) loss-of-heterozygosity and predict an increased
cancer risk.
Discrete lesions of the esophagus may be removed by endoscopic mucosal resection (EMR). This
involves a submucosal injection of saline to raise the lesion followed by snare-cautery excision. This
technique has been successfully used on neoplastic lesions arising in Barrett's esophagus and for
benign esophageal tumors.
Infectious esophagitis occurs primarily in immunocompromised patients such as those on systemic

anti-immune therapy, inhaled steroids, patients with cancer (especially those on chemotherapy), those
with diabetes, and patients with acquired immunodeficiency syndrome (AIDS). The most common
infectious agents are Candida species, Herpes simplex virus (HSV), and cytomegalovirus (CMV).
Fungal esophagitis appears endoscopically as white plaques over the inflamed mucosa. Brushings
and biopsy specimens are obtained, but brush cytology is more sensitive. Viral esophagitis manifests
as ulcers. Specimens should be taken from both the edge and the center of the ulcer. Histopathology
is usually diagnostic but multiple specimens (up to 10) may be required in patients with AIDS. Viral
culture may help provide a definitive diagnosis but may be less sensitive than histology for CMV.
Stomach
Gastric neoplasia can present as an ulcerative, polypoid, or submucosal lesion, or as thick gastric
folds. Adequate tissue sampling sometimes requires a combination of techniques. Pinch biopsy has
the highest diagnostic yield for ulcerative or polypoid masses. Multiple biopsy specimens should be
obtained from the edge of each quadrant of an ulcer and from the base. Brush cytology may increase
the yield over biopsy alone. Biopsy should be performed on polypoid lesions, and polyps greater than
2 cm should be removed when technically feasible. Gastric polypectomy may carry a higher risk of
bleeding than colon polypectomy; therefore, post-procedure acid suppressive therapy should be
considered.
EMR is used in the stomach to sample thick gastric folds to exclude malignancy, and for treatment of
early gastric cancer (EGC). Candidate early gastric cancer lesions for EMR are generally less than 20
mm and confined to the mucosa by endoscopic ultrasound or endoscopic criteria. The lesion is lifted
from the submucosa by an endoscopic fluid injection, and the lesion excised by using one of several
described techniques (see Technology Status Evaluation Report - Endoscopic Mucosal Resection).
Patients with peptic ulcer disease, gastric mucosa-associated lymphoid tissue (MALT), lymphoma,
and possibly those at increased risk for developing gastric cancer (e.g., family or personal prior history
of gastric cancer) should all have their Helicobacter pylori status determined. Tissue-based tests are
performed on endoscopically obtained forceps biopsies of gastric mucosa. These include testing the
41
sample for urease activity (rapid urease test), histologic examination for typical curved bacilli, and
culture. In untreated patients, biopsy specimens should be obtained from the lesser curvature of the
antrum near the incisura angularis. Rapid urease tests (RUT) are inexpensive, highly specific, and
can be performed in the endoscopy unit providing results in 1 hour. Less-than-perfect sensitivity has
lead to recommendations that a second test be performed if the rapid urease test is negative.
Specimens submitted for histologic examination should be assessed for the presence of inflammatory
cells and for typical curved bacilli, the latter of which may require the use of special stains. The
presence of significant gastric inflammatory cell infiltration in the absence of bacteria should prompt
additional testing with serology, a urea-breath test, or stool antigen testing. Bacterial culture allows for
determination of antimicrobial resistance but lacks sensitivity and is cumbersome to perform. The
sensitivity of these tissue-based tests may be decreased in patients using proton pump inhibitors or
antibiotics, those who have recently been treated for H pylori (but may have persistent infection), or in
the setting of gastrointestinal bleeding. In these patients, multiple biopsy specimens from the antrum
and corpus should be obtained, and a negative rapid urease test should be confirmed with an
alternative test. If possible, patients should be asked to cease taking proton pump inhibitors for at
least 1 week before testing for H pylori.
Small Intestine
Biopsy is an essential part of the investigation of patients with suspected small bowel disease. Peroral
biopsy samples have traditionally been obtained from the region of the ligament of Treitz. Endoscopic
biopsy is now more commonly used and has the advantage of being a shorter, more comfortable
procedure wherein multiple directed biopsy specimens can be obtained. Pinch biopsies will usually
yield tissue adequate for diagnosis in diffuse mucosal disease if at least 3 biopsy specimens are taken
from a site distal to the duodenal bulb in order to avoid misinterpretation of biopsy findings related to
Brunner's glands. In diseases in which involvement may be patchy, multiple biopsies from more distal
sites of the small intestine using longer and smaller-caliber endoscopes may be necessary. Biopsy
may be useful in establishing the diagnosis even in macroscopically normal tissue.
Small bowel biopsies remain the reference standard for accurately diagnosing mucosal malabsorption
syndromes. A small bowel biopsy is still considered necessary to confirm the suspicion of celiac
disease, even in the presence of positive screening blood tests (e.g., endomysial antibodies or tissue
transglutaminase). This should be done before treatment is started, because false-positive blood tests
may occur.
Infection of the small bowel may be diagnosed by histologic examination. Giardia lamblia and a
number of other protozoal agents may be associated with inflammatory changes in the small intestinal
mucosa, and detection of the mature adult organism, its trophozoites, or a component of the life cycle
in or on the surface epithelium may lead to a specific diagnosis. In some patients the morphologic
appearance may be similar to eosinophilic gastroenteritis, a diagnosis that can only be established
after parasitic disease has been excluded.
Patients with immunodeficiency, including post-transplantation or human immunodeficiency virus

(HIV) infection, may harbor agents such as Isospora belli, Cryptosporidia, Cyclospora, and
Microsporidia, which may be detected on small intestinal biopsy specimens. Other pathogens
detected on a small bowel biopsy in an immune deficient patient include CMV, fungal organisms such
as Candida species and histoplasmosis, and Mycobacterium avium-intracellulare complex. It may be
useful to use a large cup jumbo forceps rather than a conventional biopsy forceps if two biopsy
specimens are to be taken in sequence before withdrawing the biopsy forceps (Double-bite
technique). It is also advisable to use a needle to transfer the biopsy out of the forceps to the fixative
rather than shaking it off in a fixative bottle because this may alter the surface epithelium and result in
the loss of any adherent exudates.
Tumors of the duodenum should be evaluated by endoscopy and biopsy. The choice of forward- or
side-viewing instruments and sampling technique depends on the location and size of the tumor.
Duodenal, jejunal, and gastric polyps may occur in 33 to 100% of patients with familial adenomatous
polyposis (FAP). Gastric polyps in patients with FAP are most often fundic gland polyps, which have
no malignant potential, but biopsy should be considered to exclude adenoma. Duodenal polyps are
typically adenomatous and occur primarily in the ampulla or periampullary region. Upper
42
gastrointestinal polyps may appear synchronous or metachronous to the identification of colonic
polyps. Adenocarcinoma developing from periampullary adenomas is a well-recognized entity and is
the most common cause of death in patients with FAP once colorectal cancer is excluded. Although
its efficacy is yet to be established, a surveillance program is advisable. There are case reports of
pancreatitis related to endoscopic biopsy of the papilla. Despite this, complications related to
endoscopic biopsy or removal of duodenal adenomas at a distance from the papilla appears to be
uncommon.
Colon
Previous guidelines have outlined the general indications for colonoscopy and biopsy in patients with
colonic polyps and inflammatory bowel disease.
Visual evidence of a lesion warrants histopathologic evaluation. If lesions are too numerous for
removal, representative samples should be obtained for analysis. Diminutive polyps found during
screening sigmoidoscopy should be biopsied; larger polyps should be completely removed at
subsequent colonoscopy. Detection of adenomas or carcinoma is an indication for complete
examination of the colon. The published reports as to the significance of hyperplastic polyps detected
during sigmoidoscopy remains conflicted, although most gastroenterologists in the United States do
not feel that these polyps indicate an increased risk of harboring significant proximal neoplasia.
For the evaluation of colitis, endoscopy and biopsy may be useful in distinguishing between different
causes of colitis, assisting in the management of inflammatory bowel disease, and establishing the
extent of bowel involved. Biopsy specimens obtained during the acute phase of a bloody diarrheal
illness may differentiate acute self-limited colitis from an initial or recurrent attack of chronic ulcerative
colitis or ischemic colitis. Terminal ileal biopsy may be useful in the diagnosis of Crohn's disease,
infectious ileitis, and lymphoid nodular hyperplasia. Both Crohn's disease and ulcerative colitis are
associated with an increased risk of developing colorectal cancer. Surveillance colonoscopy looking
for dysplasia is recommended, beginning at 8 years of disease when the cancer risk starts to
increase. A longer delay is suggested in patients with left-sided disease only (e.g., 15 years). In
patients with pancolitis, 4-quadrant biopsy specimens taken every 10 cm, with biopsies every 5 cm in
lower 25 cm, is a frequent approach. In cases of left-sided colitis, specimens should also be taken in
the proximal colon to reassess extent of disease.
The approach to dysplastic lesions in patients with chronic colitis is evolving. When dysplastic mass
lesions are large, irregular, or associated with strictures, surgery is required. However, when typical-
appearing adenomas are encountered in a colitic segment they should be removed and the
surrounding mucosa biopsied. If the polyp is completely removed and there is no surrounding
dysplasia, then this may be regarded as an adequately treated sporadic adenoma and endoscopic
surveillance continued.
It remains unclear as to the number and location that biopsy specimens should be taken in assessing
a patient with chronic diarrhea and a grossly normal colon. Microscopic colitis is diagnosed by
compatible histologic features in a patient with chronic watery diarrhea whose endoscopic and
microbial evaluations are normal. Biopsy specimens taken during a flexible sigmoidoscopy may be
adequate to diagnose this disease entity.
Summary
Tissue sampling is useful in differentiating malignant, inflammatory, and infectious processes [C].
Techniques include pinch forceps biopsy, brush cytology, snare excision, and fine-needle aspiration
[B]. For malignant lesions, maximal yield is attained with 8 to 10 biopsies [A]. Patients with Barrett's
esophagus should undergo systematic biopsy to evaluate for dysplasia [C]. Patients with Barrett's
esophagus and high-grade dysplasia should have 4-quadrant biopsies performed every 1 to 2 cm to
detect underlying carcinoma [A, B]. Endoscopic mucosal resection may be used to remove malignant
or premalignant mucosal lesions [B]. Infectious conditions require multiple biopsies, and if ulcers are
present these should be obtained from both the center and edge; brushing and viral culture are
adjunctive techniques [B]. H pylori infection can be assessed by gastric biopsy submitted for
histologic examination or rapid urease test [A]. Biopsy of the incisura angularis gives the highest yield
for H pylori in untreated patients, but those who have been treated or are taking proton pump
43
inhibitors or antibiotics should have specimens of the corpus and fundus taken as well [A]. Gastric
polyps should be extensively sampled or removed when feasible [C]. Gastric polypectomy may carry
a higher risk of bleeding than colon polypectomy and postprocedure acid suppressive therapy should
be considered [B]. Random biopsies of the small intestine are indicated in the evaluation of diarrheal
states, celiac disease, or infections [C]. Duodenal adenomas may be sporadic or associated with FAP
and should be sampled or removed when feasible [C]. Colon lesions should be endoscopically
excised (polypectomy, EMR) or sampled if lesions are too numerous or removal is not technically
feasible [C]. In patients with acute colitis, biopsy may help establish an etiology [B]. Patients with
longstanding chronic colitis should undergo systematic surveillance to detect dysplasia, which may
indicate an increased risk of cancer [B]. In patients with diarrhea, random biopsy of normal-appearing
colonic mucosa may reveal microscopic colitis [B].
EVIDENCE SUPPORTING THE RECOMMENDATIONS
TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS
The type of supporting evidence is identified and classified for some of the recommendations using
the following scheme:
A. Prospective controlled trials
B. Observational studies
C. Expert opinion
When little or no data exist from well-designed prospective trials, emphasis is given to results from
large series and reports from recognized experts. Guidelines for appropriate utilization of endoscopy
are based on a critical review of the available data and expert consensus.
BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS
POTENTIAL BENEFITS
Appropriate utilization of tissue analysis (biopsy, snare excision, cytology, and culture) during
gastrointestinal endoscopy
POTENTIAL HARMS
There are case reports of pancreatitis related to endoscopic biopsy of the papilla. Despite this,
complications related to endoscopic biopsy or removal of duodenal adenomas at a distance from the
papilla appears to be uncommon.
CONTRAINDICATIONS
Tissue biopsy should be avoided when there is an increased potential for hemorrhage such as in
patients with coagulopathies.
Terms associated with tissue biopsy

BREAST-NEEDLE-LOCALIZATION : a procedure used to locate calcifications or thickenings in the
breast, which are detected by mammography but cannot be felt, in order to do a biopsy. Dye is
injected through a needle placed in the area to be biopsied. This is a diagnostic procedure for breast
cancer.
CONIZATION : microscopic examination of a small, wedge-shaped tissue sample surgically obtained

from the cervix for cancer cells. This procedure may be performed for the diagnosis (and sometimes
treatment) of cervical cancer, but now a colposcopy is more frequently used.
CORE-NEEDLE-BIOPSY : biopsy in which a special needle is used to remove tissue for microscopic
examination for cancer cells. This is a diagnostic procedure for a number of different cancers,
including prostate, liver, breast, and bone marrow cancer.
44
DILATION-AND-CURETTAGE
ENDOSCOPIC-BIOPSY
EXCISIONAL-BIOPSY : biopsy involving the removal of a tumor or lesion for microscopic

examination for cancer cells. This can also serve as treatment, for example in breast cancer when the
entire lump is removed, the excisional biopsy is, effectively, a lumpectomy; or in skin cancer, when the
entire suspicious growth is removed.
FROZEN-SECTION-BIOPSY : biopsy involving the rapid examination of suspicious tissue that has
been cut and quickly frozen in a machine called a cryostat. Thin slices of the tissue are then
microscopically examined for cancer.
INCISIONAL-BIOPSY : biopsy used to remove a part of a tumor or lesion for microscopic

examination for cancer cells. If cancer is diagnosed as a result of this type of biopsy, some cancer has
been left behind since only part of the tumor was removed.
LYMPH-NODE-BIOPSY
NEEDLE-ASPIRATION-BIOPSY
PERMANENT-SECTION-BIOPSY : examination of tissue for cancer cells. The tissue taken for the
biopsy is put through a series of solutions that eliminate water and fatty substances. It is then
saturated with warm liquid paraffin. When it gets hard, it is cut into thin slices, which are then placed
on slides and stained to bring out cell formations and their nuclei. This test is more accurate than
frozen section biopsy and it is always performed, regardless of whether a frozen section was done.
SHAVE-BIOPSY : type of biopsy in which a small amount of skin is removed to examine

microscopically for cancer cells. If the biopsy is positive and all the cancer has been removed, this can
also be the treatment..
STEREOTACTIC-BIOPSY : diagnostic procedure in which a scanning device is used to find a tumor

site that is difficult to locate. In a brain biopsy, the patient undergoes a CT scan with his or her head
firmly in a special device to minimize movement. The target, shown on the CT scan, is approached
with a needle through a hole made in the skull. Tissue for a biopsy is then removed with a needle.
This is a diagnostic procedure for brain cancer and breast cancer.
SURGICAL-BIOPSY
TRANSPERINEAL-BIOPSY
TRANSRECTAL-BIOPSY
SENTINEL LYMPH NODE BIOPSY

A sentinel node is the first lymph node to which a tumor drains, and therefore is the first place to
which cancer is likely to spread. In some cases, there can be more than one sentinel node. In breast
cancer, the sentinel node is usually located in the axillary nodes, the group of lymph nodes under the
arm; however, in a small percentage of cases, the sentinel node is found elsewhere in the lymphatic
system of the breast. If a doctor can feel lymph nodes during a physical exam of the breast and
underarm area that he or she suspects may be cancerous, the patient is diagnosed as "clinically
node-positive." If a patient is clinically node-negative, surgery and a laboratory analysis must be
performed to determine whether there is microscopic evidence of cancer in the lymph nodes.
Standard treatment usually involves removing a breast tumor by either lumpectomy or mastectomy
and removing most of the axillary nodes (axillary node dissection). Several complications can arise
45
from removing the axillary nodes; some reports indicate that more than 80 percent of women who
undergo a complete axillary dissection have at least one complication after surgery. These
complications are of varying severity, but can include lymphedema (swelling in the arm caused by
excess fluid buildup), numbness, a persistent burning sensation, infection, and limited movement of
the shoulder.
Previous research has suggested that the sentinel node can be used to determine if cancer cells have
spread to the lymph nodes. In sentinel node biopsy, only one or a few lymph nodes are removed for
laboratory analysis when a patient has a lumpectomy or mastectomy. Preliminary studies suggest that
if an analysis finds no cancer cells in the sentinel node, the patient is unlikely to have tumor cells in
the remaining axillary nodes.
There are two methods for finding the sentinel node. One is to inject a blue dye near the breast tumor
and track its path through the lymph nodes. The dye accumulates in the sentinel node. In a similar
technique, doctors inject a safe, small amount of a radioactive solution near the tumor and then use a
gamma detector to find the "hotspot," or the node in which the solution has accumulated. These two
techniques can also be used together. Surgeons participating in the NSABP trial will use both
methods together, and surgeons participating in the ACOS-OG trial may use either of the techniques
or the combination.
The sentinel node may provide valuable information about the status of a woman's cancer without the
complications associated with axillary dissection. While several studies have examined the correlation
between the sentinel node and the remaining axillary nodes, these are the first two randomized trials
that will compare the long-term results of sentinel node dissection with full axillary node dissection.
The two trials, while different in design, have similar goals. Both trials will examine the effect of
sentinel node biopsy and full axillary dissection on long-term survival and disease-free survival. Both
trials will also compare the side effects of the different surgeries.
Some surgeons already perform sentinel node biopsies in patients with breast cancer, although it is
still considered an investigational procedure. The concept of mapping the sentinel node was first
reported in 1977 by a researcher studying cancer of the penis. The technique was later used to study
drainage patterns of melanoma, and was first reported for breast cancer in 1993. Since then,
researchers have improved methods for finding the sentinel node, and several studies have shown
that when the sentinel node is negative, the remaining nodes are also negative in a majority of cases.
Sentinel Node Biopsy Overview
Sentinel node biopsy is a surgical procedure that doctors use to stage (determine the severity of)
certain types of cancer in patients who have been recently diagnosed with cancer. Sentinel node
biopsy is most commonly associated with staging breast cancer; however, the procedure is also
commonly used to stage malignant melanoma (a type of skin cancer). Sentinel node biopsy may also
be called sentinel lymph node biopsy or sentinel lymph node dissection.
During the procedure, the surgeon usually removes 1-5 sentinel lymph nodes (from an underarm if
breast cancer is involved) and tests those nodes to determine if cancer cells have spread to them. If
cancer cells are found in these lymph nodes, it means that the cancer might be metastasizing
(spreading through the body). Therefore, a sentinel node biopsy is an important tool for doctors to use
in determining what further treatment is necessary to get rid of the breast cancer, as well as what the
patient's prognosis is.
Lymph nodes are pea-sized structures that filter fluids that circulate through the body. The lymph
nodes collect foreign materials such as cancer cells, bacteria, and viruses from these fluids. White
blood cells, which are components of the immune system, attack the collected foreign material in the
lymph nodes. Malignant (cancerous) breast tumors may grow and spread enough that the lymph and
blood vessels that run through the breast begin to circulate the cancer‘s cells through the body, and
they may begin to grow in other locations as a result. Most cancerous breast tumors drain to the
group of lymph nodes in the underarm closest to the growing tumor.
The first node that the fluid passes through in a group of lymph nodes is called the sentinel lymph
node. The term sentinel is derived from the French word sentinelle, which means to guard over or
vigilance. Thus, the sentinel lymph node is the protective node that acts as the first filter of harmful
46
materials.
Sentinel node biopsy is a relatively new and emerging procedure. The traditional procedure for
staging breast cancer is a surgery called axillary lymph node dissection (ALND), which involves
removing all (usually 10-30) of the lymph nodes in the armpit closest to the breast tumor. The benefit
of ALND is that all of the lymph nodes can be tested for cancer cells, and the doctor can use those
findings to make a reliable determination of whether the cancer is spreading.
The drawback of ALND is that the procedure is associated with postsurgical complications such as
movement problems in the shoulder, wound infection, nerve damage, and lymphedema.
Lymphedema is swelling, most often in the arms and legs, caused by accumulation of lymphatic fluid
(fluid that helps fight infection and disease). Only 10-20% of women who undergo an ALND develop
lymphedema, but it can be a serious, untreatable condition that involves painful and chronic (long-
term) swelling of the arm.
By design a less-invasive method to stage breast cancer than ALND, sentinel node biopsy is
associated with fewer complications that may develop after the procedure. Instead of all of the lymph
nodes being removed, sentinel node biopsy involves removing an average of 2 lymph nodes.
Compared to ALND, sentinel node biopsy usually takes less time to perform, is less painful, requires a
much smaller incision, and is associated with a shorter recovery period. The main argument in
support of sentinel node biopsy is that if no cancer has spread to the sentinel lymph nodes, removing
the remaining lymph nodes is not warranted. Doing so would only increase the risk of postsurgical
complications without providing further benefits.
In addition, the accuracy involved with a sentinel node biopsy is comparable or better to those of
ALND. Surgeons who are accustomed to the procedure can identify the sentinel lymph node in 85-
98% of patients. They can also accurately determine if the cancer is spreading in 95% of patients. The
false-negative rate (percentage of cases in which no cancer cells are found in the sentinel lymph node
but are present in ―downstream‖ nodes) is less than 5%.
However, women should keep in mind that the procedure is relatively new and that the method used
in determining which lymph node is the sentinel lymph node may occasionally yield false results.
Therefore, many recommend that a woman who is interested in undergoing the procedure first check
that her surgeon has performed sentinel node biopsies 20-30 times to ensure the best possible
results.
Not all women are good candidates for sentinel node biopsy. A woman with any of the following may
be a poor candidate for the procedure:
 Lymph nodes that are palpable (can be felt through the skin)
 Breast cancer that is locally advanced
 Diffuse breast cancer (tumors in multiple parts of the breast)
 Any prior breast surgery
 Any prior radiation therapy to the breast
 A large breast tumor (greater than 5 cm in diameter)
 A breast tumor that cannot be located
 A breast tumor in a location that drains to a group of lymph nodes other than those located
under the arm
In addition, the following factors are associated with an increased risk of complications involving most
surgeries:
 Poor general health
 Long-term illness
47
 Obesity
 Advanced age
 Smoking
 Conditions that affect the blood
 Using certain medications or dietary supplements
Preparation
In preparation for a sentinel node biopsy, the patient usually undergoes tests of the blood and urine
and a mammogram (an imaging test of the breast that helps determine the location of the tumor).
The doctor may advise the patient to stop taking medications such as aspirin, anti-inflammatory drugs,
and anticoagulants (drugs that thin the blood) for a few days prior to the procedure. The doctor may
also recommend that the patient either eat lightly or avoid food and beverages altogether for a certain
number of hours (usually 8-12) prior to surgery.
To prepare for the surgery, the doctor first needs to determine which of the lymph nodes the sentinel
lymph node is. The doctor may use one or both of the following methods to locate the sentinel lymph
node:
 Radioactive tracer injection: This involves an injection of a small dose of technetium-99, a
low-level radioactive tracer. The radiation level in technetium-99 is less than standard x-ray
films involve. The doctor injects this tracer into the breast, near the tumor. The tracer then
mixes with the fluids that travel to the lymph nodes. Later, during surgery, the doctor uses a
Geiger counter (a small device that measures radiation levels) to determine which lymph
node contains the radiation. This pinpoints which lymph node is the sentinel lymph node.
Depending on the preference of the doctor, this may be injected 45 minutes to 8 hours before
the surgery. This can be injected either around the tumor or underneath the nipple/areola.
Both techniques are used and both are very successful.
 Blue dye injection: For visual confirmation of the sentinel lymph node, the doctor usually
injects a blue dye called isosulfan blue (Lymphazurin) near the breast tumor. This mixes with
the fluids that travel to the lymph nodes. When the doctor makes the incision after injecting
the dye, the sentinel lymph is colored blue. The doctor may inject this a few minutes before
the actual surgery or during the surgery. This dye turns the urine green for about 24 hours
and occasionally creates a temporary bluish stain on the breast tissue. In light-skinned
women, it also makes their skin appear a bit green (making them look like they might be
nauseated) for a few hours after surgery.
The success rate for locating the sentinel lymph node with an injection of blue dye alone is 82%. The
radioactive tracer injection is associated with a 94% success rate. The combination of both carries a
98% success rate.
Often, a sentinel node biopsy is performed during a lumpectomy or, in some cases, a mastectomy. A
lumpectomy is a minimally invasive surgical procedure that involves removing a breast tumor. A
mastectomy is a much less common surgical procedure that involves removing the whole breast. If
the doctor performs one of these other procedures in addition to the sentinel node biopsy, the woman
usually receives general anesthesia to prevent pain and awareness during surgery. Occasionally, the
woman may receive only local anesthesia, which involves numbing only the area involved in the
surgery.
During the Procedure
Sentinel node biopsy is usually performed at the same time that a lumpectomy is performed. If this is
the case, the sentinel node biopsy is usually performed first.
Depending on the preference of the doctor, the blue dye may be injected after the woman has
received anesthesia. The surgeon then uses a handheld Geiger counter to determine the exact
location of the sentinel lymph node and makes a small incision over that point. If the patient has been
48
injected with blue dye, the sentinel lymph node is colored blue. This provides the surgeon with visual
confirmation of the sentinel node.
The surgeon then removes an average of 2 sentinel lymph nodes for examination under a
microscope. Depending on the surgeon‘s practice and suspicion, a pathologist may test these nodes
for cancer while the surgeon performs the lumpectomy or the mastectomy. If cancer cells are found in
the sentinel lymph node, either at the time of surgery or when the final report from the pathologist is
available, the surgeon then performs an axillary lymph node dissection.
A sentinel node biopsy typically takes about 45 minutes to perform. If a lumpectomy is also being
performed, an extra 30-45 minutes are usually added to the total surgery time.
After the Procedure
Patients who undergo a sentinel lymph node biopsy are taken to recovery following the procedure.
Most are released from the hospital the same day.
The radioactive tracer safely dissipates, mostly in the urine, within 24-48 hours.
The incision usually heals within a few weeks. Regular activities can be performed within a few days.
Next Steps
If the sentinel lymph node was not examined during surgery, the pathologist tests it for cancer cells
soon after. The doctor addresses the findings of the examination during a follow-up visit.
If the pathologist finds cancer cells in the sentinel lymph node, the patient usually undergoes a follow-
up surgery to undergo an axillary lymph node biopsy. This involves removing and testing the
remaining lymph nodes in the area of the original biopsy for cancer cells. Regardless of the findings,
almost all women who undergo surgery to stage breast cancer or to remove breast tumors also
undergo chemotherapy or radiation therapy to kill any remaining cancer cells.
Risks
Sentinel node biopsy is a procedure that is designed to minimize risks. It is a useful tool for staging
breast cancer and determining what further treatment is appropriate to offer the patient the highest
possible chance of survival. Sentinel node biopsy is also an emerging procedure designed to
minimize the risks associated with an axillary lymph node dissection.
The most significant risk is that a sentinel node biopsy results in a determination that cancer cells are
not metastasizing in the body when, in fact, they really are. This is called a false-negative result. This
is a reason that a woman should ensure that her surgeon has performed the procedure several times
(20-30) with accurate results before she undergoes the surgery.
Rarely, a patient can have an allergic reaction to the blue dye. The most mild and most common type
of allergic reaction is hives. Hives are usually seen within 24 hours of the dye injection. A very rare
patient will have a severe allergic reaction, but this usually happens within minutes of the injection of
the dye.
Other possible risks of a sentinel node biopsy may occur and are usually mild in severity. These
include the following:
 Pain, discomfort, or numbness (usually short-lived) in the area of the incision
 Bluish discoloration of the breast tissue (usually temporary) following injection of the blue dye
 Drowsiness
 Vomiting and nausea
The following are possible complications following most surgical procedures:
 Infection
 Bleeding or bruising
49
 Scarring
Results
Surgeons who are experts at sentinel node biopsy can identify the sentinel lymph node in 85-98% of
patients. They can also accurately determine if the cancer is spreading in 95% of patients. The false-
negative rate is less than 5%.
50
Tissue Biopsy – Techniques and Interpretation
Dr A.K. Mandal
Soft tissue tumours are a highly heterogeneous group of tumours that are morphologically classified
according to the adult tissue they resemble. The diagnosis of soft tissue tumours presupposes that
the pathologist has a modicum of:
 Clinical information
 Adequate tissue
 Well processed tissue
From pathologist point of view excision biopsy is preferred because these are high volume.
The most important step in the approach to soft tissue tumours is the careful assessment of the gross
specimen and a basic evaluation of haematoxylin stained slide. Based on this assessment an initial
differential diagnosis are made. Haematoxylin – Eosin stained sections represent the mainstay of
diagnosis but in case of dilemma the routine Haematoxylin – Eosin sections have to be supported by
ancillary techniques such as:
 Special stains (PAS, Reticulin)

 Cytochemistry (Myeloperoxidase, chloracetoestrase etc)
 Immunohistochemistry (Cytokeratin, LCA, Desmin etc)
 FISH and ISH technique
 TUNNEL staining
However, out of all these immuno-histochemistry is one of the latest developments in the field of
tumour diagnosis. It has now become an inseparable part of histopathological diagnosis of soft tissue
and other tumours. Its advantages are :
 Extremely specific
 Very sensitive
 Morphological details are preserved
 Can be done in tissues from archives
 Detects hormone receptors and other prognostic and therapeutic markers
Immuno-histochemistry is the first choice for most diagnostic situations. Panels of antibodies are
required to differentiate carcinomas, lymphomas, sarcomas and round cell tumours.
However, it has certain disadvantages:
 Expensive
 Needs proper technique and interpretation
 Nonspecific staining if not done properly
Guidelines for choosing immunohistochemical markers:

Epithelial Tumour:
 Cytokeratin (CK)
 Epithelial membrane antigen (EMA)
Mesenchymal Tumour:
 Vimentin
 Smooth muscle actin (SMA)
 Desmin
Neuronal Tumours:
 S-100
51
 Chromogranin
 Neuron specific enolase (NSE)
 Synaptophysin
Lymphoid Tumours:
 LCA
 T Cell
 B Cell
Histiocytic tumours:
 CD 68
Method of immuno-histochemistry
Principle: The primary antibody (generally in mice) binds to their specific antigen on the
tumour cell. A secondary antibody against the primary antibody is added (anti mouse
in rabbit). The secondary antibody is tagged with biotin. When avidin is added 4
molecules of avidin can get attached to one molecules of biotin and each avidin is
farther attached with multiple molecules of Horse radish peroxidase (HRP). HRP
changes DAB into a chromogenic compound which has a golden brown colour and
can be visualized under ordinary light microscope.
Method:
1. Tissue has to be rehydrated and brought to water.
2. Antigen retrieval has to be done if required
3. Nonspecific sites in the tissues has to be blocked with hydrogen peroxide
4. The slides are then washed in PBS buffer three times for 30 minutes.
5. Nonspecific sites in the tissues are then blocked with milk block
6. The slides are then washed in PBS buffer three times for 30 minutes
7. The tissues are incubated with the primary antibody overnight in a humidity chamber at 4oC
8. The slides are then washed in PBS buffer three times for 30 minutes.
9. The tissues are incubated with secondary antibody for 30 minutes at room temperature in a
humidity chamber.
11. The tissues are incubated with tertiary antibody for 30 minutes at room temperature in a
humidity chamber.
13. DAB substrate is added and incubated until desired staining is achieved.
14. Development of the colour is stopped by washing tissue with distilled water
15. Slides are stained with haematoxylin for 4 minutes.
16. The slides are dehydrated and mounted.
52
Fluid, electrolyte & blood management - Surgeons' Viewpoint
Dr. Rakesh Kumar, Ekta Gupta, Neera R Gupta
Need to know about fluid, electrolyte and Blood management
Imbalances in the body milieu in terms of fluid, electrolyte and blood homeostasis are common in
surgical patients, be it routine surgery or emergency surgery. If not identified and then managed in
time, these imbalances can have serious implications in terms of both surgical outcome and complete
physiological and neurological recovery. An aware surgeon should be able to guess which of his
patients are potentially at risk of such imbalances, who are the ones suffering from sub-clinical levels
of these abnormalities, what are the clinical presentations that can be due to these abnormalities,
initiate the correct management strategies, ask for help from his anaesthesiology colleagues as and
when required, and work in association with the anaesthesiology team to optimize these patients
throughout the peri-operative period.
It is also important to understand that the ill effects of fluid, electrolyte and blood abnormalities are
further compounded during surgery because of fluid and electrolyte loss and translocation during long
duration surgeries involving many body cavities and requiring major tissue handling. The time
available before some of the emergency surgeries is not enough to fully correct these abnormalities,
especially if the surgery is being planned to treat the situation causing/deteriorating these
abnormalities. Both the surgeon and the anaesthesiologist have to understand that such patients are
likely to fare poorly until the trend towards improvement is closely monitored and ensured throughout
the surgery also, especially once the incriminating event is brought under control during surgery (e.g.,
ruptured spleen removed or peritonitis drained and perforation sealed).
FLUIDS AND ELECTROLYTES
Assessment of fluid, electrolyte balance
The assessment involves history, examination and investigations, which should be timely and
relevant. The limited time available in surgical patients (routine or emergency) should be used
judiciously by the surgical and anaesthesiology teams in assessing the degree of problem and then
setting out on the path of its correct and timely management.
History:
„Looking‟ for fluid and electrolyte loss
By simply asking relevant history one may find hints of fluid and electrolyte loss from various sites
such as the GIT (bleeding, vomiting, diarrhea, fistula etc.), kidneys (diuresis, diabetes insipidus,
osmotic diuresis etc.), skin (burns, large exudative lesions such as Steven Johnson Syndrome etc.),
and traumatized sites (long bone fractures, ruptured liver/spleen, haemothorax etc.).
On the other hand, some situations cause abnormalities by redistribution (third space losses,
vasodilation causing situations like anaphylaxis or sepsis, nephritic syndrome, cirrhosis etc.), or loss
within the body (conditions causing capillary leak such as anaphylaxis, sepsis, eclampsia etc. or those
causing sequestration such as intestinal obstruction, peritonitis etc.).
It is important to realize that some of these losses are easily assessable (vomiting, diarrhea, urine,
fistula or drain collections – abdominal, thoracic, thigh etc.), while many of the losses have to be
‗guessed‘. This guessing process is greatly helped by the scientific knowledge of the body secretions
(Table 1).
Thus a 60kg patient in intestinal (ileal) obstruction for two days and history of no intake and 4
episodes of vomiting of nearly half litre volume each would have lost:
 ~ 2 litres in vomits
 4-5 litres within the intestine in sequestration (not 14 litres):
o Secretions beyond obstruction are expected to be mostly absorbed
53
o Production of secretion proximal to obstruction should decrease as there is nothing
to ‗digest‘ and there is intra-luminal pressure due to already present secretions of the
first day
o Some of the secretions may be absorbed even proximal to obstruction
And the approximate loss of electrolytes can also be guessed (~700 meq of Na+ and Cl- and 210 meq
of HCO3- and 160 meq of K+ - for ~7 litres of loss of fluid above colon) (Table 1). In addition, he would
have suffered deficit because of no intake (~100 mL/h = 4.8 litres + 180 meq of sodium + 120 meq of
potassium + other ions like Mg++, Ca++ etc.).
Table 1: Composition and daily production of gastrointestinal secretions
Fluid source Production per Sodium mEq/L Potassium Chloride Bicarbonate

24 hours mEq/L mEq/L mEq/L
Saliva 1.5 L 2-10 20-30 8-18 30
Stomach 2.5 L 60-100 10-20 100-130 0
Pancreas 135-145 5-10 70-90 95-120
Bile 135-145 5-10 90-130 30-40
1.5 L
Jejunum 120-140 5-10 90-140 30-40
Ileum 80-150 2-8 45-140 30
Colon 2.5 L 60 30 40 -
TOTAL 8L 540 150 540 150
Looking for symptoms of dys-electrolytemia

Hypernatremia/hyponatremia presents as central nervous system symptoms like confusion, weakness
and lethargy and usually occurs due to a water problem and not a sodium problem.
Hyperkalemia/hypokalemia gets reflected in ECG changes (palpitations due to dsyrrhythmias) and
neuromuscular weakness. Hypocalcemia may produce neurological (paresthesia, seizure, dementia),
neuromuscular (muscle spasm, tetany) or cardiovascular (hypotension, dysrrhythmia) symptoms
when ionized calcium is <1 mmol/L. Hypercalcemia though rare, may present with nausea, vomiting,
constipation, abdominal pain, confusion, delirium. Hypophosphatemia may cause profound skeletal
muscle weakness and CNS dysfunction.
It is obvious from this that symptoms of common electrolyte disturbances are non specific and difficult
to separate from underlying illness. It is rather difficult to identify the type of electrolyte lost unless
supplemented by other evidences (probable site of fluid loss) as mentioned above.
Examination
A patient with cold clammy skin, dry mucus membranes, sunken eyes, obtunded mentation and
muscle weakness is likely to be suffering from severe hypovolemia. Further, the vital signs like
tachycardia, hypotension, decreased urine output and decreased central venous pressure (CVP) are
indirect indicators of volume deficit.
Dys-electrolemia may present as CNS signs such as obtundation, confusion, inebriation; peripheral
nervous system signs such as muscular weakness, sluggish reflexes, paresthesia, muscle spasm;
CVS signs such as irregular pulse, hypotension; respiratory system signs such as inadequate
respiratory effort or tachypnea.
When supplemented by bed-side monitoring, fluid and electrolyte abnormalities may show up as
alterations and abnormalities in oxygenation (SpO2), heart rate and rhythm, arterial and central
venous pressure and urine output. More advanced monitoring such as pulmonary artery occlusion
pressure and cardiac output monitoring may be used if available and in common use (say cardiac
centre)
Investigations
Physical signs of intravascular volume depletion may be further confirmed by patients demonstrating
high levels of BUN and serum creatinine, low urinary Na +, high urinary osmolality, metabolic acidosis
(ABG analysis) and increased haematocrit (Table 2). Severe hypovolemia may result in lactic acidosis
owing to compromised tissue perfusion. Monitoring gastric mucosal CO2 using a monometer and
54
mucosal blood flow using laser Doppler may help to assess regional gut perfusion, one of the earliest
tissues to be compromised in hypovolemia.
Table 2: Investigations suggestive of intravascular volume depletion

Normal range Suggestive of hypovolemia
BUN (mmol/L) 2-14 >15
S. creatinine (µmol/L) <150 >150
Urinary Na+ (mmol/L) >30 <15
Urinary osmolality (miasmal/L) 400-800 >800
S. lactate (mmol/L) <1.5 >2
For assessing electrolyte abnormalities, estimation of serum Na+, K+, Cl-, HCO3- , Mg++, Ca++ and
PO4+++ etc. is required. This helps in assessing and quantifying the deviations.
 Water deficit (in litres) when there is hypernatremia = [0.6 x total body weight x {(serum
Na+ /140) – 1}]
 Sodium deficit (mmol) = [0.5 x lean body weight x (140 – S. Sodium)]
 Potassium deficit (mmol) = 100 mEq deficit causes decrease in serum potassium by ~0.3
mEq/L
 Calcium deficit (mmol) = 200 mg of elemental calcium deficit causes decrease in serum
calcium by ~1 mg/dL
 HCO3- deficit (mmol) = Base deficit x 0.3 x body weight in kg
Management of Fluid and Electrolyte Abnormalities
Goals
Goals of fluid and electrolyte therapy are to meet the basal fluid requirements, replace losses, restore
or maintain hemodynamic stability, enhance microvascular blood flow so that oxygen is delivered to
tissues and to maintain aerobic cellular metabolism. Complete restoration of normal milieu is not
always, in fact most of the times, possible before taking up the patient for surgery because the
surgical condition itself may be the major cause of abnormalities, and at times there may be limitation
of available time. However, it is almost always possible to initiate a trend towards normalcy before
putting the patient under the knife.
Table 3: Composition and Characteristics of some of the commonly used fluids
Pentastarch 6% Gelatin Ringer‘s Isotonic 5% 3%

6% (Hestril, Tetrastarch (Hemaccel) lactate (Normal) Dextrose Hypertonic
Parameters Hestar) (Voluven) Saline saline
Volume effect 100% for 4-6 100% for 4-6 70% for 2-3 25-30% 25-30% ~10% for ~340% for
hrs hrs hrs for 30-60 for 30-60 30-60 min 30-60 min
min min
Distribution Intravascular Intravascular I/Vasc+IS I/vasc+IS I/vasc+IS I/vasc+IS+IC Each mL
ONLY ONLY (70:30) (25:75) (25:75) (8:24:68) pulls 2.4mL
from IS, IC
till effect,
then similar
to NS
Osmolarity 308 308 301 301 308 278 1024
(mOsmol/L)
+ + + + + +
Electrolyte Na = 154; Na = 154; Na = 145; Na = 154; Na = 154; --- Na = 512;
- - - - - -
content Cl = 154 Cl = 154 Cl =145; Cl =111; Cl = 154 Cl = 512
+ +
mmol/liter K =5 K =5
++ ++
Ca =6 Ca =2;
-
HCO 3 =29
Maximum 33 ml/kg 50 ml/kg Not Not Not Not
dose/day mentioned mentioned mentioned mentioned
Risk of Least Least High --- --- ---
anaphylactoid
reactions
Capillary Demonstrated Demonstrated Nil --- --- ---
plugging
I/Vasc = intra-vascular; IS = interstitial; IC = intra-cellular
55
What Fluid and How much
It will be guided by a number of things, including some established from history, examination and
investigations as elaborated above. These are:
 Estimation of total fluid loss and the type of electrolytes lost (see example on page 2 and
Table 1)
 The body compartment that needs replenishment
 Urgency of replenishing various body compartments
 Composition and characteristics of the available fluids (Table 3). In this regard, it is better to
understand that
o The body fluids are distributed so that in a sixty kilo adult, nearly three litres are there
in the intravascular compartment (plasma volume), 9 litres are in the interstitial
compartment (together making 12 litres of extra-cellular compartment), and finally 24
litres are in the intravascular compartment.
o Electrolyte containing fluids (crystalloids) can not enter the cells and are thus
distributed evenly in the intravascular and interstitial compartments after the
equilibration time. Thus one litre of Ringer‘s lactate will have 250 mL in the intra-
vascular and remaining 750 mL in interstitial compartment within half an hour.
o Water can move freely in all compartments. Dextrose 5% (1 litre) will behave like
water once the dextrose is utilized and thus will offer ~85 mL increase in plasma,
~250mL in interstitial and 635 mL increase in intra-cellular compartment after few
minutes of infusion
o Colloids are dispensed in balanced electrolyte solutions, and depending upon their
colloid osmotic characteristic and colloid concentration either hold on to the complete
volume of electrolytic solutions they are dispensed in (e.g., 6% starch solutions), or
some of the solution they are dispensed in (e.g., 3.5% gelatin solutions), or rarely
more than the dispensing solution by pulling fluid from extravascular compartment
(e.g., 10% starch solutions)
 Alterations in the monitored parameters as the fluid is being administered (described later)
Rate of replenishment
The rate of replenishment will depend upon many factors:
 The condition of the patient
 The condition of the cardiovascular system in terms of its capacity to tolerate sudden fluid
load. The final interplay between intra vascular volume and cardiovascular dynamics
determines the homeostasis. These may change during the course of replenishment and thus
need constant monitoring. In practical terms, to test the volume status of the circulation a fluid
challenge is given. As many intravascular compartment measurements (pulse, BP, urine
output, peripheral perfusion, CVP, RA and LA pressure) as possible are made. 200-300 ml of
intravenous fluid is rapidly given and intravascular measurements repeated. This manoeuvre
is repeated until the normal circulating intravascular volume is replenished.
 Situations that demand quick intra-vascular replenishment with minimum loading warrant use
of colloids that stay put in the intra-vascular compartment and yet provide electrolytes
 The time available for achieving stabilization
 Correction of electrolyte abnormalities required
o Hyponatremia - Calculate sodium deficit (see above)
 Acute symptomatic
 Give hypertonic saline (3%)
 Rate of correction should be less than 2mEq/L/hr and less than 15
mEq/L over first 24 hours
 Chronic symptomatic (higher risk of neurological complications related to
therapy)
 3 % saline till resolution of symptoms or 10% correction of serum
sodium @ <1.5 mEq/L/hr initially
 Asymptomatic
 Treat underlying cause of decreased effective circulating volume
o Hypokalemia - Calculate sodium deficit (see page 3 above)
 IV infusion usually @ 20 mmols/hour; in rare and emergency circumstances
may go up to 40 mmols/
56
o Hypocalcemia- a total of 200 mg of elemental calcium may be necessary to raise the
total serum calcium by 1 mg/dL.10 ml of 10% of calcium gluconate solution
(elemental calcium =9mg/ml= 0.46 mEq) is infused over ten minutes
o Hypomagnesaemia - for urgent hypomagnesaemia an intravenous bolus of 2-3 g
magnesium sulphate followed by an infusion of 10 g magnesium sulphate over the
next five hours should be considered. Monitor ECG, deep tendon reflexes and Mg++
levels
o Hypernatremia - Calculate water deficit (see page 3 above)
 Treatment is water repletion
 Replace half the deficit over 12-24 hr
 Do not correct more rapidly than 2meq/L/hr
 Replace remaining deficit over 48 hours
 If hemodynamic instability is present, give isotonic saline until stable before
replacing water deficit with hypotonic saline
 If volume overload is present, treat with diuretic and 5% dextrose.
Monitoring Management
Successful and effective management will be seen in the form of diminishing symptoms, improving
mentation, hydration and improvement in CVS and respiratory parameters. The heart rate will
decrease and arterial pressure, CVP, PAOP, CO and urine output will improve.
The investigations suggesting intravascular volume depletion (Table 2) and serum values of
electrolytes should start showing trend towards normalcy.
Generalizations
A normal healthy adult loses 1500-2000 ml/day in urine, 500-1000ml/day as insensible loss through
skin and lungs and 100-200ml through GIT. He requires sodium requirement @1.5 mmol/kg/day.
Potassium @ 1-1.5 mmol/kg/day, glucose (obligatory) @ 0.1g/kg/hour (17% more dextrose than
glucose because it produces less calories per gram).
Thus a 60 kg adult male daily requires ~2400 ml fluid, 90mmol sodium, 60-90mmols potassium and
150g dextrose, which can be met by infusing 1-2 vacs of Ringer‘s lactate, 4-5 vacs of 5% dextrose out
of which 3 containing 1 ampoule (20mmol) of potassium each.
Normally potassium is not administered in the first 24 hour after surgery as endogenous release of
potassium from tissue trauma and catabolism warrants restriction. Other electrolytes such as chloride
calcium, magnesium do not require short term replacement but must be supplemented during chronic
intravenous fluid maintenance.
So called ‗golden hour‘ of resuscitation infers that there is a short window of time when it is important
to correct hypovolemia and not just maintain BP, so that the perfusion of ‗non vital‘ organs especially
splanchnic organs is maintained. Splanchnic hypoperfusion has been shown to predispose to multi
organ dysfunction syndrome (MODS).
Initial access to body fluids is traditionally by cannulation of the intravascular space (intravenous
access). The other spaces are not directly accessible. Each fluid‘s distribution can largely be
predicted. Colloid/ blood goes to intravascular space, crystalloid solution is distributed to interstitial
space and 5 % dextrose to intracellular space. Thus 5% dextrose would be an inappropriate and
inefficient fluid to resuscitate the intravascular compartment for shock.
Principles of fluid and electrolyte management are the same whether it is for multi trauma, sepsis,
diabetic ketoacidosis or perioperative period. Priorities are to urgently correct hypovolemia and shock,
then the serum potassium and finally to correct the total body water and other electrolyte
abnormalities including sodium, phosphate, magnesium and calcium. Apart from hypovolemia,
urgency and rate of correction of other abnormalities depends on the rapidity with which they
developed.
When we administer an intravenous fluid we have to ask ourselves as to which body fluid
compartment the administered fluid will be distributed and on what basis we estimate those
compartments in order to give correct amount and composition. Moreover we must be familiar with
57
drugs and techniques used to manipulate fluids in those spaces and the danger of over and under
filling.
The intravascular space is uniquely amenable to drug manipulation either by vasodilatation/

vasoconstriction. Elimination of fluid from the interstitial and the intracellular spaces can be achieved
by drugs such as diuretics, aldosterone/ angiotensin antagonists or by techniques like dialysis/ultra-
filtration. For example a patient with peripheral oedema in the face of hypovolemia and hypotension
can be given a solution containing colloid to correct hypovolemia and increase colloid osmotic
pressure simultaneously while a diuretic decreases the interstitial space. Similarly glucose insulin and
potassium can be given to move water into the intracellular space.
PERIOPERATIVE MANAGEMENT OF BLOOD LOSS AND TRANSFUSION
Introduction
Blood transfusion refers to the administration of blood and blood components (e.g., autologous blood,
allogeneic whole blood, red blood cells, fresh frozen plasma [FFP], platelets, and cryoprecipitate).
Over 60% of all homologous blood (also called allogeneic or bank blood) transfusions are given
during perioperative period. Thus it is important for the anaesthesiologists and surgeons to be aware
of the basic principles involved in blood administration.
Blood transfusion is a serious matter in view of likely hazards associated in the form of haemolytic
transfusion reactions (with a mortality of 20-60%), non-haemolytic transfusion reactions,
immunosuppression, transfusion-related acute lung injury (TRALI), and Infection transmission. In
addition, even when these hazards are avoided, stored blood transfusion leads to temporary
abnormalities in the form of lower oxygen carrying capacity, hyperkalemia, hypocalcemia,
hypothermia, coagulopathy, hypothermia and microaggregates.
Peri-operative blood transfusion, thus, should be used with the sole aim of getting the best out of this
potentially life saving fluid only when clearly indicated and in amounts it is indicated, so that only the
minimum number of patients and health care providers are exposed to its life threatening potentials.
General principles
 Potential patients for blood transfusion should be evaluated pre-operatively
o For organ ischemia (e.g., cardiorespiratory disease), which may influence the ultimate
transfusion trigger for red blood cells (e.g., haemoglobin level)
o For coagulopathy (e.g., use of warfarin, clopidogrel, aspirin), which may influence
transfusion of non–red blood cell components
o For presence of congenital or acquired blood disorders
o Using investigations haemoglobin, haematocrit, and reviewing coagulation profiles if
they are appropriate and available. Additional laboratory tests should be ordered
based on a patient‘s condition (e.g., clinical coagulopathy) or institutional policy
o In cases where peri-operative coagulopathy is anticipated, laboratory monitoring
should include determination of platelet count, prothrombin time (PT) or INR, and
aPTT. Other tests may include fibrinogen level, assessment of platelet function,
thromboelastogram, d-dimers, and thrombin time.
 For elective surgery, patient preparation should include discontinuing anticoagulation therapy
for a sufficient time in advance of surgery, if clinically possible. If sufficient time has not
elapsed, surgery should be delayed until the effects of these drugs dissipate (e.g.,
approximately a week for clopidogrel, several days for warfarin depending on patient
response and the administration of reversal agents (vitamin K, FFP etc.). The risk of
thrombosis versus the risk of increased bleeding should be considered when altering
anticoagulation status.
 Erythropoietin should be administered when possible to reduce the need for allogeneic blood
in certain selected patient populations (e.g., renal insufficiency, anemia of chronic disease,
refusal of transfusion).
 Where autologous blood is required or preferred, the patient may be offered the opportunity to
donate blood before admission. However, preoperative anemia may be induced in addition to
an increase in total intraoperative autologous or allogeneic transfusions, as well as costs
 A visual assessment of the surgical field should be periodically conducted by both
anaesthetist and surgeon to assess the presence of excessive microvascular bleeding (i.e.,
58
coagulopathy). Standard methods for quantitative measurement of blood loss (e.g., suction
and sponge) should be used
 Equally, if not more, important is to monitor the adequacy of perfusion and oxygenation of
vital organs using conventional monitoring systems (e.g., blood pressure, heart rate, oxygen
saturation, urine output, electrocardiography). Special monitoring systems should be used
when appropriate (e.g., echocardiography, mixed venous oxygen saturation, blood gases).
 When appropriate, intraoperative or postoperative blood recovery (e.g., cell salvage) and
other means to decrease blood loss (e.g., deliberate hypotension) may be beneficial. Acute
normovolemic hemodilution may also be considered
 Desmopressin or topical haemostatics such as fibrin glue or thrombin gel should be
considered when excessive bleeding occurs.
 When traditional well-tested options for treating excessive microvascular bleeding (i.e.,
coagulopathy) have been exhausted, recombinant activated factor VII should be considered.
 Periodically check for signs and symptoms of bacterial contamination, TRALI, and haemolytic
transfusion reactions, including urticaria, hypotension, tachycardia, increased peak airway
pressure, hyperthermia, decreased urine output, hemoglobinuria, and microvascular bleeding.
 Before instituting therapy for transfusion reactions, stop the blood transfusion and order
appropriate diagnostic testing.
RBC and Whole blood (not used anymore in most centers) Transfusion
 Don‘t transfuse for wrong reasons: for volume expansion alone, to promote wound healing, to
promote well being, just because it has been donated, just because it is in the OT, or to treat
anemia even if treatable cause is identified and there is enough time available.
 Determine the need on individual basis and not on the basis of a particular appearance (looks
very pale or weak!) or value (<10g/dl Hb). In this regard it is to be understood
o There is no single transfusion trigger. It is a dynamic variable based on individual
judgment, cardiopulmonary status, preoperative Hb & intravascular volume. In
addition, intraoperative Hb and blood volume estimation are inaccurate due to fluid
therapy and intercompartmental fluid shift, and even invasive monitoring like DO2,
VO2, Extraction ratio are not organ specific
o Hb/Hct of 6g/dl /18% is acceptable
- As intraoperative hemodilution (isovolemia maintained)
- Post-operatively in healthy patients and those with compensated chronic
anemia with preoperative Hb of 8gm/dl
o Hb/Hct of 8g/dl /24% is acceptable
- Pre-operatively if the expected blood loss <500ml
- Post op after cardiac surgery
- In ASA II / III patients intra / post operatively
o Hb/Hct of 10g/dl /30% is required
- Pre-operatively in patient of ↓Cardiac reserve, CAD
- Post operatively if there is increased post operative oxygen demand
- In patients requiring prolonged IPPV
- In patients with age > 65 yrs
 Measure haemoglobin or haematocrit when substantial blood loss or any indication of organ
ischemia occurs.
o Red blood cells should usually be administered when the haemoglobin concentration
is low (e.g., less than 6 g/dl in a young, healthy patient), especially when the anemia
is acute.
o Red blood cells are usually unnecessary when the haemoglobin concentration is
more than 10 g/dl.
o These conclusions may be altered in the presence of anticipated blood loss. The
determination of whether intermediate haemoglobin concentrations (i.e., 6–10 g/dl)
justify or require red blood cell transfusion should be based on any ongoing indication
of organ ischemia, potential or actual ongoing bleeding (rate and magnitude), the
patient‘s intravascular volume status, and the patient‘s risk factors for complications
of inadequate oxygenation. These risk factors include a low cardiopulmonary reserve
and high oxygen consumption.
59
 Maintain adequate intravascular volume and blood pressure with crystalloids or colloids until
the criteria for red blood cell transfusion listed above are met. Adequate quantities of red
blood cells should be transfused to maintain organ perfusion.
 Platelet transfusion
o In surgical or obstetric patients with normal platelet function, platelet transfusion is
rarely indicated if the platelet count is known to be greater than 100-109/l and is
usually indicated when the count is below 50-109/l in the presence of excessive
bleeding.
o Vaginal deliveries or operative procedures ordinarily associated with limited blood
loss may be performed in patients with platelet counts less than 50-109/l.
o Platelet transfusion may be indicated despite an apparently adequate platelet count if
there is known or suspected platelet dysfunction (e.g., the presence of potent
antiplatelet agents, cardiopulmonary bypass) and microvascular bleeding.
o The determination of whether patients with platelet counts between 50 and 100-109/l
require therapy, including prophylactic therapy, should be based on the potential for
platelet dysfunction, anticipated or ongoing bleeding, and the risk of bleeding into a
confined space (e.g., brain or eye).
o When the platelet count cannot be done in a timely fashion in the presence of
excessive microvascular bleeding (i.e., coagulopathy), platelets may be given when
thrombocytopenia is suspected.
o When thrombocytopenia is due to increased platelet destruction (e.g., heparin-
induced thrombocytopenia, idiopathic thrombocytopenic purpura, thrombotic
thrombocytopenic purpura), prophylactic platelet transfusion is ineffective and rarely
indicated.
 FFP transfusion
o FFP is not indicated solely for augmentation of plasma volume or albumin
concentration.
o Fresh frozen plasma should be given in doses calculated to achieve a minimum of
30% of plasma factor concentration (usually achieved with administration of 10–15
ml/kg FFP), except for urgent reversal of warfarin anticoagulation, for which 5–8 ml/kg
FFP usually will suffice.
o Four to five platelet concentrates, 1 unit single-donor apheresis platelets, or 1 unit
fresh whole blood (most institutions no longer have fresh whole blood available from
the blood bank) provide a quantity of coagulation factors similar to that contained in 1
unit FFP.
o FFP transfusion is indicated for
- Correction of excessive microvascular bleeding (i.e., coagulopathy) in the
presence of a PT greater than 1.5 times normal or INR greater than 2.0, or an
aPTT greater than 2 times normal
- Correction of excessive microvascular bleeding secondary to coagulation
factor deficiency in patients transfused with more than one blood volume
(approximately 70 ml/kg) and when PT or INR and aPTT cannot be obtained
in a timely fashion
- Urgent reversal of warfarin therapy
- Correction of known coagulation factor deficiencies for which specific
concentrates are unavailable
- Heparin resistance (antithrombin III deficiency) in a patient requiring heparin
 Transfusion of cryoprecipitate
o If possible, a fibrinogen concentration should be obtained before the administration of
cryoprecipitate in a bleeding patient. Transfusion of cryoprecipitate is rarely indicated
if fibrinogen concentration is greater than 150 mg/dl.
o Transfusion of cryoprecipitate is usually indicated
- When the fibrinogen concentration is less than 80–100 mg/dl in the presence
of excessive microvascular bleeding
- Fibrinogen concentration is between 100 and 150 mg/dl and there is potential
for anticipated or ongoing bleeding and the risk of bleeding into a confined
space (e.g., brain or eye).
60
- To correct excessive microvascular bleeding in massively transfused patients
when fibrinogen concentrations cannot be measured in a timely fashion
- For patients with congenital fibrinogen deficiencies.
- Bleeding patients with von Willebrand disease if specific concentrates are not
available
o Each unit of cryoprecipitate contains 150–250 mg fibrinogen. Each unit of FFP
contains 2–4 mg fibrinogen/ ml. Therefore, it should be noted that each unit of FFP
delivers the equivalent amount of fibrinogen as 2 units cryoprecipitate
SUMMARY
Fluid, electrolyte and blood homeostasis and requirements change dramatically in the surgical
patients due to problems for which surgery is required, surgery itself, anesthetic interventions and
drugs, peri-operative fasting, co-morbidities, and peri-operative responses to anesthesia and surgery.
It is useful for both the surgical and anaesthesiology teams to understand the basics of fluid,
electrolyte and blood management and then work together to take the patient as close to normalcy as
allowed by the time available on hand. For this both the teams need to choose the right fluid and
blood component and in the right amount, monitoring both the expected beneficial and likely
deleterious effects at all times.
References
1. International Practice of Anaesthesia. Eds. Prys-Roberts C, Brown Jr. B; Butterworth Heinemann, Oxford 1996
th
2. Textbook of Critical Care. 5 ed, Eds. Fink MP, Abraham E, Vincent JL, Kochanek M. Elsevier; Philadelphia,
Pennsylvania 2005
th
3. Miller‘s Anesthesia. 6 ed. Ed. Miller RD Elsevier; Philadelphia, Pennsylvania 2005
4. Practice Guidelines for Perioperative Blood Transfusion and Adjuvant Therapies Anesthesiology 2006; 105:198–
208
5. WHO. Blood Transfusion safety: The clinical use of blood in Medicine, Obstetrics, Pediatrics, Surgery and
Anaesthesia, Trauma and Burns. Geneva 2003
6. Guidelines of Consensus Conference Of RBC Conservation (1988)
7. Kumar R, Chakraborty I and Sehgal R. Anesth Analg 2002; 95: 1154-61
8. Kapoor D, Kumar R, Seghal R, Kumar S. Anesthesiology 2004: A-192
61
Investigations in Thyroid Disorders
Dr. Ravi Kashyap
Thyroid disorder, benign or malignant, will show as structural or functional abnormality involving entire
or partial gland. Structural abnormality can be diffuse or nodular. Nodular involvement can be solitary
nodule, dominant nodule or multinodular. The functional status of the thyroid gland can be categorized
into hyperthyroid, hypothyroid or euthyroid. Thyroid disease is a combination of functional and
structural abnormalities of thyroid gland, which is correctly defined by various investigations.
FUNCTIONAL ASSESSMENT:
The clinical manifestations of thyrotoxicosis (hyperthyroidism) or hypothyroidism are so diverse that

diagnosis based on clinical features alone lacks both sensitivity and specificity. Hence, reliance is
placed on measurements of circulating thyroid hormones (thyroxin T4 & tri-iodothyronine T3) and
thyroid stimulating hormone (TSH) to confirm or rule out thyroid dysfunction. A normal serum TSH
value in ambulatory patients without associated disease or pituitary dysfunction has a high negative
predictive value in ruling out both primary hypothyroidism and thyrotoxicosis.
First line thyroid function test (T4, T3 and TSH) should be carried out in:
 Patients with palpable thyroidal swelling
 Patients with classical symptoms of hyperthyroidism or hypothyroidism
 Patients with mild symptoms suggestive of thyroid disease and family history of thyroid
hyperthyroidism or hypothyroidism
 Pregnant woman, or those contemplating pregnancy, with symptoms suggestive of
hyperthyroidism or hypothyroidism, or with family history of thyroid disease.
 To rule out congenital hypothyroidism in neonates.
Between TSH and T4 measurements, TSH is a preferred one as single initial test because of its
superior sensitivity in detecting the earliest stages of thyroid disease. Assessment of untreated
subjects now often begins with measurement of TSH alone, with T4 and T3 assays added only if TSH
is abnormal, or if an abnormality of TSH secretion is suspected. Serum TSH loses its diagnostic value
when pituitary function is abnormal, serum T4 then becomes the front-line test.
A serum free T4 estimate will generally follow from an abnormal TSH value, but during critical illness,
free T4 estimates often show non-specific abnormalities. This lack of specificity is the basis for a
recommendation against routine assessment of serum TSH and free T4 during acute critical illness in
the absence of risk factors, or clinical features suggestive of a thyroid disorder. It follows that free
hormone measurement will better reflect the physiological effects of the hormone than total hormone
measurements, especially when binding proteins are abnormal.
Estimation of free T4, or total T4 linked to a measurement of the thyroid hormone binding ratio, is
standard whenever TSH is abnormal, or in situations where TSH alone is known to give an inaccurate
indication of thyroid status.
Two key assumptions in any method of free T4 estimation are (i) that the dissociation of bound
hormone with sample dilution is similar in samples and standards, and (ii) that samples and standards
show identical protein binding of the assay tracer. If either of these conditions is breached, the assay
is likely to give inaccurate results.
Serum T3 (total or free) measurement should be done only in:

1. Patients suspected to have thyrotoxicosis in whom serum free T4 values are normal and
serum TSH values are low, to distinguish between T3 –thyrotoxicosis and subclinical
1.
thyrotoxicosis.
2. During antithyroid drug therapy to identify patients who have persistent T3 excess, despite
normal or low serum free T4 values.
3. For diagnosis of amiodarone–induced thyrotoxicosis, this should not be based on T4 excess
alone because of the occurrence of euthyroid hyperthyroxinemia in many amiodarone treated
patients.
62
4. Serum T3 measurements also may be useful for calculation of the serum T3:T4 ratio. In
patients with Grave‘s thyrotoxicosis, a high ratio (>0.024 on a molar basis or >20 calculated
as ng/µg) that persist during antithyroid drug treatment suggests that remission is unlikely.
This ratio usually is lower in patients with iodide–induced thyrotoxicosis or thyrotoxicosis
caused by thyroiditis than in those with thyrotoxicosis caused by Grave‘s disease.
5. Other situation in which measurements of serum T3 may provide useful information are to
detect early recurrence of thyrotoxicosis after cessation of antithyroid therapy and to
establish the extent of active hormone excess during high-dose therapy with T4 or after
intentional T4 overdosing.
Owing to its short plasma half-life, measurement of serum T3 is not useful in assessing the
effectiveness of treatment with T3; the serum concentration highly dependent on the interval between
dosage and sampling. As for T4, serum total T3 concentrations are influenced by alterations in
binding proteins.
Low serum T3 concentrations have little specificity or sensitivity for the diagnosis of hypothyroidism.
Many patients with non thyroidal illness have low values, and some hypothyroid patients have normal
values.
The diagnostic accuracy of total hormone measurements would equal that of free hormone if all
patients had similar binding protein concentrations. Unfortunately, serum TBG abnormalities that
distort the total:free hormone relationship, are commonly encountered in clinical practice. Additionally,
some patients have abnormal thyroid hormone binding proteins or autoantibodies that render total
hormone measurements diagnostically unreliable. Therefore free T3 or free T4 will better reflect the
physiological effects of the hormone than total hormone measurements, especially when binding
proteins are abnormal.
Thyroglobulin
This iodinated 660 kDa dimeric glycoprotein, which is the backbone for thyroid hormone
biosynthesis, is normally detectable in serum and is released in excess in a wide variety of
situations where thyroid tissue is overactive, inflamed or proliferating. It is used as a tumor
marker for differentiated thyroid cancers. Undetectable serum levels suggest absence or
suppression of thyroid tissue. Low levels reveal factitious hyperthyroidism in hyperthyroid
individuals with low radioiodine uptake.
Because elevation of serum thyroglobulin concentration occurs in a wide range of thyroid

disorders, interpretation of results always requires knowledge of (i) the clinical context, (ii) the
serum TSH concentration and (iii) whether thyroglobulin antibodies are present. For optimal
thyroglobulin assay, it may be preferable to use radioimmunoassay for samples that are
antibody-positive, with use of the more sensitive immunometric techniques to confirm
absence of functioning tissue in antibody negative samples.
Thyroid peroxidase antibody (TPOAb)

This entity, previously termed antimicrosomal antibody, is closely linked with Hashimoto‘s
thyroiditis (45-80% of cases) and autoimmune hypothyroidism (upto 95%). TPOAb is useful
investigation for predicting prognosis in mild thyroid dysfunction.
Antithyroglobulin (Anti-Tg) antibody

These are present in 12-30% of Graves‘ disease and 35-60% of patients with autoimmune
hypothyroidism. The results of anti thyroid peroxidase and anti-thyroglobulin antibody tests
can differ in areas of iodine deficiency.
Anti-thyroglobulin antibodies interfere with measurement of thyroglobulin, and should be

assayed in patients with differentiated thyroid cancers in whom serial thyroglobulin
measurements are planned.
TSH Receptor Antibody (TRAb)

These are detectable in 70-100% of patients with Graves‘ disease and upto 20% of patients
of autoimmune hypothyroidism. Measurement of stimulatory anti-TSH-receptor antibodies,
which are themselves the cause for hyperthyroidism, is the most sensitive antibody test for
63
Graves‘ disease. An anti-TSH-receptor antibody test may also help to determine the cause of
hyperthyroidism in pregnancy. Antibody presence in hypothyroidism may indicate reversible
disease as the blocking antibody disappears.
Calcitonin and CEA in Medullary Tumors

The calcitonin assay provides a convenient screening procedure in families with this genetic
trait. Secretion of calcitonin by medullary cancer is remarkably increased by calcium or
pentagastrin infusion. This procedure can be helpful in establishing a diagnosis. At present
the infusion of pentagastrin (0.5 µg/kg over 5 seconds), with determination of calcitonin levels
at 0, 1, 2, 5, 10, and 15 minutes, appears to be the best test. Basal CT values are normally
under (depending on the laboratory) 30 pg/ml. Values of 30-100 after pentagastrin indicate
hyperplasia, and values over 100 typically indicate the presence of cancer. Calcitonin should
drop to levels of < 30 pg/ml if the tumor is completely removed surgically. It should be noted
that excess production of CT is not unique for medullary cancer, but can occur with
granulomatous diseases and other cancers.
The C cells also produce carcinoembryonic antigen (CEA) in large amounts. Serum CEA
levels are elevated in medullary cancer with the same frequency as are CT levels. Although
CEA determination provides another parameter to follow, it does not offer any obvious
advantage, and lacks the specificity of CT determinations. Tumor dedifferentiation is
associated with a fall of CT and increasing CEA, which is an ominous sign.
Radioactive Iodine Uptake Test (RAIU)

RAIU test may be helpful in the following clinical conditions:
 To confirm hyperthyroidism
 To calculate therapeutic dose of I-131
 To determine autonomous thyroid tissue (i.e. toxic nodules, - combined with thyroid scan)
 To determine the cause of thyrotoxicosis
The most useful role of RAIU test is in determining the etiology of thyrotoxicosis.
Thyrotoxicosis simply refers to excess thyroid hormone in the body and may be due to
overactivity of the thyroid gland (hyperthyroidism), or other causes such as inflammation of the
gland (thyroiditis) or ingestion of excess thyroid hormone. In "true hyperthyroidism" - RAIU uptake
will be high while thyrotoxic patients with thyroiditis or who abuse thyroid hormones will have a
low RAIU.
Etiologies resulting in an Increased RAIU

1. Hyperthyroidism (Grave's disease or TSH-secreting pituitary adenoma)
2. Rebound following abrupt withdrawal of antithyroid meds
3. Long term antithyroid therapy: Prolonged therapy may result in decreased circulating
levels of T4- hence TSH levels will increase. This will accentuate radioiodine uptake.
4. Enzyme defects
5. Iodine starvation
6. Lithium Therapy
7. Early Hashimoto's Thyroiditis (Patients rarely present at this stage, RAIU is typically
normal [early] or decreased [late] in these patients)
8. Rebound during recovery from subacute thyroiditis
Etiologies resulting in a Decreased RAIU

Blocked Trapping:
 Iodine load (most common). An iodine load can "falsely" lower the RAIU through two
mechanisms: 1) producing the Wolf-Chaikoff effect 2) causing a dilutional effect, i.e.,
diluting the I-123/I-131 atoms with nonradioactive I-127 atoms.
 Exogenous thyroid hormone replacement depressing TSH levels
 Ectopic thyroid: Struma Ovarii
Blocked Organification:
- Antithyroid medication (PTU): Note- Tc-99m uptake should not be affected
Parenchymal Destruction:
- Acute, Subacute and Chronic Lymphocytic Thyroiditis
64
Hypothyroidism:
- Primary or Secondary (insufficient pituitary TSH secretion)
- Surgical/Radioiodine Ablation of Thyroid
Thyroid Suppression Test

The thyroid suppression test is based on the premise that normal thyroid activity is
suppressed by exogenously administered thyroid hormone. The test is used to determine the
autonomy of a hot nodule or diffusely enlarged gland. A baseline scan and uptake are
performed. The patient is then placed on T3 (Cytomel 25 ug TID [50-75 ug daily] for 7 days)
or T4 (Eltroxin 100ug OD for 3 weeks) to suppress TSH production. Iodine uptake should
normally fall to 50% of presuppression value in a non-autonomously functioning nodule.
Indications:
 Early Graves' disease with borderline hyperthyroidism or in euthyroid Graves' disease
(patients presenting with ophthalmopathy but normal function tests).
 Nodules that are indeterminate (warm or nondelinated) where a distinction between
hot and cold is unclear. A repeat scan on cytomel (T3) or levothyroxine therapy with
suppression of TSH may reveal whether the thyroid nodule is autonomous (hot) on
non autonomous (cold). A non-autonomous nodule should be treated as a cold
nodule and require further evaluation.
Perchlorate Discharge Test

This test is used to identify congenital or acquired organification defects which most
commonly involves the enzyme iodide peroxidase. In normal subjects, radioiodine when taken
up by the thyroid is immediately organified and bound to thyroglobulin. However, in patients
with defects in peroxidase activity (usually hypothyroid), trapped radioiodine is rapidly
discharged when sodium perchlorate (an inhibitor of thyroid iodide trapping) is administered.
Thyroid uptake is then determined between 2 and 4 hours after administration of the dose.
Potassium perchlorate 109 mg/kg is then administered orally and a repeat measurement of
RAIU performed in 30 to 60 minutes. A decrease in RAIU greater than 10-15% following
perchlorate administration is indicative of any organification defect. The test is rarely
performed since the treatment for primary hypothyroidism is thyroid hormone replacement
regardless of the cause or site of defective thyroid hormone synthesis.
STRUCTURAL ASSESSMENT:
Ultrasonography
Because of recent advances in technology, ultrasonography is highly sensitive in determining
the size and number of thyroid nodules. By itself, ultrasonography cannot reliably be used to
distinguish a benign nodule from a malignant nodule. However, combining high-resolution
sonography with Doppler and spectral analysis of the vascular characteristics of a thyroid
nodule holds promise as a useful tool in screening thyroid nodules for malignancy. Studies
have shown that the risk of malignancy is lower in nodules with a predominantly perinodular
pattern than in nodules with an exclusively central vascular pattern. Furthermore, if the
vascular characteristics of thyroid nodules are combined with their ultrasonographic
parameters, including a halo, microcalcifications, cross-sectional diameter, and echogenicity,
the predictive value of this imaging approach may increase.
Thyroid ultrasonography can be helpful in certain cases when it is used to guide FNAB.
Image-guided FNAB may be particularly helpful in the assessment of nonpalpable or small
nodules, nodules with cystic components, or nodules that are difficult to access (eg, posterior
or substernal nodules).
65
Other radiological modalities
CT or MRI is generally not cost-effective in the initial evaluation of solitary thyroid nodules.
Such studies may be useful in the assessment of thyroid masses that are largely substernal.
Also, in some cases CT-guided FNAB may be helpful.
If malignancy is suspected, a chest radiograph should be obtained, given the high incidence
of early metastases to the lungs. However, chest radiography has only 60% sensitivity in this
setting and, therefore, should be confirmed with postoperative CT and scintigraphy.
Fine-needle aspiration biopsy

FNAB has emerged as the most important step in the diagnostic evaluation of thyroid
nodules. FNAB as highly accurate, with mean sensitivity higher than 80% and mean
specificity higher than 90%. The accuracy of FNAB in diagnosing thyroid conditions highly
depends on the cytopathologist's expertise and experience and the technical skill of the
physician performing the biopsy. Routine use of FNAB in the evaluation of thyroid nodules
can reduce the need for diagnostic thyroidectomy by 20-50% while increasing the yield of
cancer diagnoses in thyroid specimens by 15-45%.
Provided that adequate cellular material is available, FNAB of thyroid nodules can be used to
categorize tissue into the following diagnostic categories: malignant, benign, thyroiditis,
follicular neoplasm, suspicious, or nondiagnostic. In the malignant category, FNAB can be
used to distinguish papillary carcinoma, medullary carcinoma, anaplastic carcinoma, and
carcinoma metastatic to the thyroid gland, and it can be used to distinguish malignant
lymphoma from other disease. FNAB can also help in reliably diagnosing colloid nodules,
Hashimoto thyroiditis, and subacute thyroiditis.
The main weakness of FNAB involves hypocellular aspirates and aspirates with high follicular
cellularity. Hypocellular aspirates may be observed in cystic nodules, or they may be related
to biopsy technique. The addition of ultrasonography to guide FNAB sometimes reduces
technical errors. In addition, on-site verification of the adequacy of the specimen by a
cytotechnologist or a pathologist is likely to reduce the rate of nondiagnostic specimens.
Aspirates characterized by high follicular cellularity suggest follicular neoplasm; however,

FNAB cannot be used reliably to distinguish a benign follicular neoplasm from a malignant
neoplasm. In addition, aspirates that are highly cellular with Hürthle cells can be observed
with benign or malignant Hürthle-cell neoplasms and with some cases of Hashimoto
thyroiditis.
Advances in cytologic analysis may increase the predictive value of FNAB of thyroid nodules
in the future. For example, the incorporation of immunocytochemical studies, as well as
genetic and molecular profiling of aspirates, may improve the accuracy of minimally invasive
diagnostic techniques.
Medullary Carcinoma of thyroid arises from C cells of or the parafollicular cells of thyroid
which are derived from the neural crest tissue. MTC have an ominous histologic pattern, with
solid masses of cells with large vesicular nuclei. There may be considerable associated
fibrosis, and deposits of amyloid.
Scintigraphy and PET

Once a nodule has been confirmed as having a solid component, radioiodine and Tc99m
pertechnetate scintigraphy are used to determine the activity of the nodule as cold, warm, or hot.
Radioiodine is more physiological but gives more radiation burden to the patient. Tc99m
pertechnetate is similar to Iodine in uptake, but is not organified.
Vascularity of a nodule can be objectively ascertained by taking dynamic images of thyroid after bolus
administration of radiotracer. The information obtained gives insight in vascularity and the washout
pattern- a parameter useful to differentiate benign from malignant nodule. Avascular cold nodule or
nodules with slow washout are usually benign. This observation has high positive predictive value for
benign nodules.
66
Scintigraphy also can be used to detect ectopic thyroid tissue or identify the thyroid tissue that will be
lost with thyroglossal duct cyst removal, requiring lifelong thyroid hormone replacement.
The activity of the nodule determines the next step in therapy. Hot nodules often require antithyroid
medications before surgery, whereas cold nodules have a much higher incidence of malignancy.
Scintigraphy also is used postoperatively to exclude the presence of metastases, especially after total
thyroidectomy.
A cold nodule on 99mTc pertechnetate or 131 I scan requires further evaluation by scintigraphy. If
bilateral non-functioning nodules are identified, possibility of familial MTC, MEN-2A or MEN -2B
should be considered.
99m
Tc(V)-DMSA is also a useful agent to image medullary carcinoma of thyroid, but the role is limited
to follow-up after surgery. 99mTc (V)-DMSA positive and 99mTc pertechnetate negative scan is strongly
suggestive of MTC.
Other radiotracers used for MTC are 201Tl, 99mTc MIBI, 123 131
I/ I MIBG, 111
In-Octreotide and 123 131
I/ I&
111
In-CEA (radiolabelled monoclonal antibodies).
Positron-emission-tomography (PET) with 18F-fluorodeoxyglucose is at present primarily an

investigational tool and has some role in differentiated thyroid neoplasms imaging, particularly in the
evaluation of radioiodine negative metastatic disease. The introduction of new specific radiotracers
(proliferation or receptors markers), will further increase its utility in future.
The objective way of management of thyroid disorders is with the functional and structural
assessment using methods and techniques described above.
67
Nodular Goiter
Gyan Chand, Dr. Amit Agarwal
Definition:
A thyroid nodule is a discrete lesion within the thyroid gland that is palpably and/or
ultrasonographically distinct from the surrounding thyroid parenchyma.
Thyroid nodules are extremely common with 7% of adult having palpable nodules and up to 50%
adults having nodule visible on ultrasound.
Around 5% of thyroid nodules are malignant thyroid nodules may occur as isolated, often incidental
findings or they may be associated with systemic features of thyrotoxicosis or hypothyroidism they
may be solitary or may present as a dominant nodule in the multinodular goiter.
Solitary nodules have a higher likelihood of being malignant although the prevalence of cancer is
similar between patients with a solitary nodule and patients with multiple nodules.
Etiopathogenesis:
The exact etiology is not known.
Multiple risk factors are noted -

 Familiar clustering
 Iodine deficiency
 Constitutional factors i.e. male gender
 Other
o Cigarette smoking
o Goitrogens
o Emotional Stress
o Certain drugs
o Infection
Classification of thyroid nodules
Benign
Multinodular goiter
Hashimoto thyroidities
Simple or haemorrhagic cysts
Follicular adenomas
Subacute thyroiditis
Colloid nodule
Malignant
Papillary carcinoma
Follicular carcinoma
Hurthle cell carcinoma
Medullary carcinoma
Anaplastic carcinoma
Primary thyroid lymphoma
Metastatic malignant lesion
Clinical features
Patient usually present with a nodular swelling in the neck, for cosmetic reasons or for compression
symptoms. Rarely patient may present with signs of hyperthyroidism.
Majority of thyroid nodules are benign, clinical assessment & investigation is essential to exclude
malignancy.
68
History
Age & Sex (Thyroid nodules are commoner in women & elderly)
Residence (common in iodine defficiencant area)
Prior history of exposure to radiations
Symptoms
Obstruction such as dysphagia & dysphonea
Change in voice, recurrent laryngeal nerve compression
Duration of symptoms with rapidity of change in symptoms
Systemic features of hyper or hypothyroidism
Family history of malignancy.
Examination
Goiter / swelling - look from front & side of neck localized or diffuse, single or multiple.
Movement with swelling
Prominent veins (may be sign of retrosternal extension)
Other swelling in the neck
Size and number of thyroid swelling
Consistency – cystic, firm or hard
Presence of dominant nodule
Movement with deglutition
Position of trachea & evidence of tracheal compression- strider / kocher‘s test
Evidence of retrosternal extension- seen in 20% patients manifest as prominent veins over
neck & chest wall, Pambertons sign positive, dull note on percussion over chest wall.
Evidence of cervical lymphadenopathy
Position of carotid artery
Signs of Hyper or Hypothyroidism
 Signs that may suggest malignancy are-

 Firm/ hard or fixed nodule, ill defined nodule on palpitation
 Hoarseness / loss of voice.
 Presence of palpable cervical lymph nodes
Investigations
Thyroid function test – TSH
Thyroid ultrasound
Fine needle aspiration biopsy
CT / MRI
Thyroid scan
Thyroid function test-

Serum TSH level should be measured in every patients presenting with a clinical abnormality in the
thyroid.
If TSH normal - further analysis of thyroid function tests is often not required.
If TSH is high - free T4 & thyroid peroxidase antibody (TPOAb) should tested, high level of this
antibody suggest Hashimoto disease, which may occasionally present with palpable nodule.
If TSH is low - then serum T4 & T3 should be measured to further investigate hyperthyroidism,
thyroid stimulating hormone receptor antibody (TRAb) is useful to distinguish Grave‘s disease from
toxic multinodular goiter.
The situation of a nodule that associated with hyperthyroidism (toxic nodule) play an important role in
determining how the clinical lump is managed. In these cases nuclear medicine scan should be
performed & FNAB may not be necessary.
69
Ultrasound of thyroid
The role of ultrasound in the investigation of the clinically abnormal thyroid gland is increasing, the
main reason for the widespread use of thyroid sonography are availability, low cost, limited discomfort
to the patient and non-ionizing nature.
Sonography has many favourable features, such as detection of non palpable nodules, estimation of
nodule size / goiter volume (monitoring the effect of therapy) and guidance for the FNAB.
It is now recommended as a part of the routine investigation of a palpable thyroid nodule.
Ultrasound allows correlation of the clinical features with the ultrasound appearance, allows the
nodule to be characterized further.
The risk of malignancy is the same for that found as incidental impalpable lesion as for nodules of the
same size that are palpable. Therefore it is important to assess each nodule individually on ultrasound
looking for the features suspicious of malignancy.
Ultrasound features suspicious of malignancy include -

 Irregular margins
 Presence of microcalcification
 Hypoechogenecity
 Absence of a halo
 Predominantly solid composition
 Intranodular vascularity
 Regional lymphadenopathy
 Invasive growth
As ultrasound alone is limited in its ability to distinguish benign from malignant nodules, further
investigations of palpable nodules with FNAB is usually required even when the lesion has a benign
appearance on ultrasound.
Fine needle aspiration biopsy-

Fine needle aspiration biopsy is indicated for nearly all palpable and symptomatic nodule and should
considered in other nodules more then 1cm. Fine needle aspiration biopsy should also be performed
for smaller nodule (< 1 cm ) that have suspicious clinical or ultrasound features.
The technique involves the use of a 5–20 ml plastic syringe with a 21–27 gauge needle, the skin is
cleaned with alcohol and may be infiltrated with 1-2 ml of 1% lidocaine. The needle attached to the
syringe is inserted perpendicular to the anterior surface of neck, negative pressure is applied and as
soon as bloody fluid in the hub of the needle appears, pressure is released and the needle withdrawn,
no fluid should be followed by FNAB of any residual solid component. the management of multiple
incidental thyroid nodules seen on ultrasound is controversial biopsy of all these nodules is neither
practical nor necessary. Focus should be on nodules that show concerning features on ultrasound
and other nodule should probably be monitored with ultrasound. there is no consensus however on
the optimal follow up interval for the incidental asymptomatic lesions. Nodules that do not routinely
required FNAB are solitary nodules associated with a suppressed TSH (toxic nodules), these nodules
should be assessed with thyroid scintigraphy, if the nodule is hot the risk of malignancy is minimal and
FNAB is therefore usually not required. These nodules can then be managed with radioactive iodine
or surgery.
FNAB is a simple and useful test but its usefulness is dependent on obtaining an adequate specimen
and having it examined by an experienced cytopathologist, there is no consensus on the classification
of thyroid cytology.
In general FNAB can be reported as –

 Insufficient ( technically unsatisfactory )
 Benign
 Atypical or suspicious
 Malignant
70
Table:- FNAB results of thyroid nodules
Frequency (range)
Benign (no evidence of malignancy) 69% (53-90%)
Colloid nodule
Thyroiditis (chronic, acute, or subacute)
Cyst
Suspicious 10% (5-23%)
Follicular5 neoplasm
Normofollicular
Marcofollicular
Microfollicular (fetal)
Trabecular and solid (embryonal)
Oxyphilic cell type (Hurtle cell)
Malignant 4% (1-10%)
Follicular carcinoma
Papillary carcinoma
Medullary carcinoma (C cell carcinoma)
Undifferentiated (anaplastic) carcinoma
Lymphoma
Metastasis (rare)
Non-diagnostic (insufficient) 17% (15-20%)
The main difficulty is in cases of follicular neoplasm, it can be impossible to distinguish a follicular
adenoma (a benign lesion) from a follicular carcinoma on cytological assessment. Follicular lesion
therefore often required excision and its capsule before a definitive diagnosis can be made, rate of
insufficiency vary from 15-20%, in more than half of these cases a sufficient sample will be achieved if
the test is repeated. Fine needle aspiration biopsy has a sensitivity of 65-98%, specificity 72-100%,
positive predictive value 50-96%, false – negative rate 1-11% and false positive rate 0-7% with an
overall accuracy of 95%. It is a quick, safe, cost effective and reliable investigation in the detection of
thyroid malignancy. It will give an atypical or suspicious result in up to 10% of specimens, surgical
excision of these nodules for full histopathological assessment is recommended as 20% may be
malignant, the accuracy of FNAB increase when it is performed under ultrasound rather than manual
guidance. Fine needle aspiration biopsy may be seen as an accurate test to determine which nodules
should be managed surgically and which may be managed conservatively.
Nodules that is benign on FNAB & show no suspicious features on clinical & ultrasound assessment
may be managed conservatively, those showing atypical or malignant cytology should be surgically
removed, nodule returning non-diagnostic result may be assess with repeat FNAB or manage
conservatively, if there are no suspicious features on clinical & ultrasound assessment.
CT and MRI scan-

Computerized tomography and MRI scan are not routinely indicated in the assessment of thyroid
nodules, they cannot reliably distinguish benign from malignant lesions, the main indication for these
scan is to determine the presence and extent of retrosternal extension and the presence and degree
of tracheal compression when obstructive symptoms are present. and MRI scan are also useful when
malignancy is likely and further information on the extent of disease such as involvement of great
vessels, trachea and regional lymph nodes is required. Another advantage of computed tomography
and MR is the possibility for planimetric volume estimation, especially useful in irregularly enlarged
goitres.
Antithyroid Peroxidase (anti-TPO) antibodies-

Antithyroid peroxidase antibodies are seems to be relevant because thyroid antibodies are found
approximately 10% of population and consequently, autoimmunity may well coexist within a goiter,
that can be seen as diffuse or focal lymphatic infiltration in an enlarged gland may represent chronic
autoimmune thyroiditis. the anti TPO status is also relevant for therapy with radioiodine (131I), because
these antibodies constitute a risk factor for thyroiditis, hypothyroidism and transition in to Grave‘s
disease
71
Serum Calcitonin-
This hormone is a marker of Medullary thyroid carcinoma (MTC) and the serum levels correlates with
the tumor burden. With modern assay serum calcitonin is below 10pg/ml in 99% of healthy subjects
and is slightly higher in man then women, the normal upper limit of serum calcitonin after stimulation
with pentagastrin is approximately 40pg/ml, if the level exceeds 100pg/ml, strongly indicates the
presence of MTC or C- cell hyperplasia.
Routine estimation of serum calcitonin in nodular goitres is not recommended because it is not cost
effective.
Other causes of raised calcitonin are
 Impaired renal function

 Pseudo-hypoparathyroidism
 Treatment with proton pump inhibitors
Thyroid Scintigraphy-
A nuclear medicine scan may not always be necessary in the initial assessment of the simple nodular
goiter, there are some clinician however, who recommended its routinely. Scintigraphy alone is unable
to reliably distinguish malignant from benign nodules. The main clinical indication for thyroid
scintigraphy is hyperthyroidism (suppressed TSH) is present. Nodules with a high uptake by
scintigraphy almost never harbour clinically significant malignancy although exceptions have been
reported.
The risk of malignancy among the cold nodules is reported 8-25% or even higher. Thyroid
scintigraphy is also useful to identify ectopic thyroid tissue or occult hyper functioning tissue and may
have a role in the up of same neoplasm.
Treatment
A. Multinodular Nontoxic Goiter-
There is no ideal treatment for the simple goiter.
a. Iodine supplement
It seems to be an adequate approach, because goiter development is strongly associated
with even mild iodine insufficiency. A daily dose of 400g iodine during 8month is as effective
as 150g L-T4 in reducing the size of defuse goiter. But the iodine supplementation appears
to increase the incidence of papillary thyroid cancer and Lymphoid thyroiditis.
b. Suppressive levothyroxine therapy

It has been recommended that diffuse euthyroid endemic goiter treated with 200g iodine
combine with 10g L-T4 for at least 6 months followed by iodine alone. The aim is to
suppress TSH level to <0.5 mU/L. in general a goiter reduction of 15-40% can be expected
within 3 months, but the gland returns to pre-treatment size just as soon after withdrawal, so
treatment needed lifelong. This lifelong treatment to avoid goiter recurrence, the natural
history of the disease is progression towards hyperthyroidism due to autonomous function of
the thyroid nodules, Therefore, L-T4 treatment is unfeasible in many patients, presently this
therapy not recommended except in small diffuse goitres in the young, where it is least
necessary .
c. Surgery
Surgery is indicated when there is / are

 Malignancy proven on FNAB
 Possible malignancy ( atypical , suspicious finding on FNAB)
 Symptoms of compression from the goiter (dysphagia or tracheal compression, a sensation of
choking alone without imaging evidence of tracheal compression is a ‗soft‘ indication for
surgery).
 Hyperthyroidism(this may treated with surgery or with radioactive iodine or medications)
72
 Patient‘s choice(usually for cosmetic reasons when nodules are >3cm)
 Other indications (i.e.-when an adequate sample cannot be obtained by FNAB on several
attempts or when a nodule that has shown benign features on ultrasound and FNAB has
grown during a period of observation)
Surgical procedure most commonly performed are -
 Hemithyroidectomy – this is indicated for :-

o A solitary nodule that is hot or atypical on FNAB.
o A dominant nodule in the context of a multinodular goiter where only one lobe is
significantly affected.
o Differentiated thyroid cancer <1cm.
 Total thyroidectomy – this is indicated for :-

o Thyroid malignancy, except small well differentiated cancer.
o Hyperthyroidism due to Grave‘s disease when thyroid eye signs are present or
medical management is on successful or contraindicated.
o Symptoms or signs of compression of the trachea or esophagus.
o Multinodular goiter where both lobes are significantly affected.
o Patient choice for cosmetic reasons related to large goiter.
 Other surgical option-

o Removal of nodule only – nodulectomy
 Subtotal thyroidectomy-
They generally have no advantages over operations listed above and rates of complications are
similar. these procedures also have additional disadvantage over total thyroidectomy or
hemithyroidectomy such as recurrence of symptoms or development of cancer in the remaining
tissue. These problems may require re-operation. Re-do thyroid surgery is associated with a higher
risk of complications such as recurrent laryngeal nerve injury and permanent hypocalcemia compared
to initial surgery. Thyroid surgery requires meticulous care to avoid damage to surrounding structures
but is now a low risk procedure in experienced hands.
Complications includes –
 Hemorrhage (an common but potentially fatal complications – occurs in <1% of cases)
 Voice disturbance or hoarseness due to injury to the recurrent laryngeal nerve (may be
temporary or permanent damage occurs in <1% of cases), injury to external branch of the
superior laryngeal nerve can cause less obvious voice changes. Patient may complain of an
inability to project their voice and easy fatigability of their voice.
 Hypocalcemia – due to damage of the parathyroid glands or their blood supply (requires
calcium supplementation. May be temporary or permanent (2-3%).
 Hypothyroidism is expected and is permanent following total thyroidectomy. It may also
occur temporarily or permanent following hemithyroidectomy.
d. Radioactive Iodine therapy (131I )
It is primarily used for toxic (hyper functioning) nodules and toxic nodular goiter. It is become
evident that radioiodine therapy also results in shrinkage of the thyroid gland even if
hyperthyroidism persist, due to this effect an gland volume, radio iodine has been used during
the last two decades in the treatment of nontoxic nodular goiter. Large dose is required for the
large goiter specially >100ml goiter volume requires hospitalization and isolation.
Because the thyroid malignancy is more prevalent in substernal goiter, but if they are proved
by FNAB as benign then they may also benefited from the radioactive iodine therapy. The
goiter reduction is more pronounced in diffuse nontoxic goiter then multinodular goiter. In
general patients are satisfied with radio iodine therapy. The goiter reduction might be
augmented by increasing the amount of radioactivity. For that the pre-treatment with
recombinant human TSH causes a more homogenous distribution of radioiodine within the
nodular gland by stimulating the radioactive iodine uptake, relatively more in cold area then in
73
hot areas. There is an early goiter enlargement caused by radiation may be seen, therefore
caution should be taken if sever tracheal compression is present. But generally radioactive
iodine therapy is well tolerated. Radiation induced thyroiditis may be seen in few percentage
of cases occurring within the few months after therapy. This self limiting condition is
characterized by sever tenderness of thyroid, elevated ESR and fever.
There is also short period of hyperthyroidism caused by dumping of stored thyroid hormone in
to circulation. This Grave‘s like disease occurred typically within 1-3 months after treatment,
probably due to release of antigenic component from follicular cell that trigger to appearance
of TSHR antibodies. Radioactive iodine therapy of any thyroid disorder always includes a
certain risk of thyroid hypo-function, increasing with time. Some study shows there is
increased incidence of thyroid cancer after radioactive iodine therapy, but the overall cancer
mortality was actually reduced. Therefore in nontoxic goiter, restrict the use of radioactive
iodine for >40 years patients unless surgery is absolutely contraindicated.
B. The Solitary Nodule :-

Because the aspects of surgery, I131 and I & R L-Ta therapy has been detailed regarding
multinodular goiter we will focus on the newest modalities regarding treatment of the
solitary nodule.
Incidentaloma
The clinically not palpable nodules found incidentally during USG neck for any other region is
known as incidentaloma. The nodules measuring 1-1.5cm or larger are usually not palpable when
located deep in the glands need US-guided FNAB.
The proportion of malignancies among incidentalomas <1.5 cm, ranges from 3-6% similar to the
frequency for palpable nodules. Thus suggesting that incidentalomas can not be left untreated.
If incidentaloma sized is 1 x 1 cm and without clinical suspicion of malignancy, treated

conservatively under surveillance or suppressive therapy.
Solitary cold nodule-
a. T4 therapy
It is still common practice to use thyroid suppression in the management of solid thyroid
nodules in the euthyroid patient. This treatment is intended to shrink existing nodules,
considered to be a favourable sign, indicating that the nodules are benign and therefore do
not require surgery. This method is also used to prevent the occurrence of new nodule. Most
evidence suggests that changes in nodule size are independent of serum TSH levels, and
treatment is more effective in patients with smaller solid nodules.
20% or less of solitary nodules will actually regress with L-T4 treatment but re-growth in seen
after cessation of therapy.
b. Surgery
The main indications for surgery are malignant or suspicious cytological features and
symptoms due to the nodule itself, be it pressure related or cosmetic. Hemithyroidectomy is
surgery of choice. Minimally invasive video assisted thyroid lobectomy using endoscopic
techniques is being practice in few centres. Postoperative thyroid suppression to avoid
recurrence is questionable.
c. Percutaneous absolute ethanol injection therapy ( PEIT )-

It can relive the clinical symptoms in 50% of patients, based on a nodule volume reduction of
approximately 50%. Repeat injection result in a reduction in nodule volume of 80%.
74
Solitary hot nodule-
Indication of treatment-
 Large nodule size
 Causing compression of the adjacent structures.
 Cosmetic complaints.
 Prevent hyperthyroidism.
a. Radioactive iodine therapy-

It is a simple, cost effective and safe procedure. A cure rate of 75% and a thyroid volume
reduction of 40% after a single dose of radioactive iodine.
Side effects are few, consist of hypothyroidism in approximately 10% after 5years and seen
unrelated to any type of dose planning.
b. Surgery-
Surgery and radioactive iodine are both effective and the choice among depends largely on
their availability, some clinical features & the personal preference of the patient and physician.
 Either can also result in hypothyroidism.

 Surgery is often preferred for younger patients and larger nodules or clinical or cytological
suspicion of malignancy.
 Radioactive iodine therapy preferred for elderly patients and those with smaller nodules.
 The preferred minimum operation is a hemithyroidectomy.
The frequency of complications due to surgery depends on several factors, and experience tends
to reduce the rates with specialized training.
Recurrence after surgery is rare and frequency of hypothyroidism is low.
c. Percutaneous ethanol injection therapy (PEIT)-
The sclerosing properties of ethanol have been recognized for many years and the mechanism of
action is a coagulative necrosis and concomitant small vessel thrombosis. The procedure is
performed under US- guidance and on an outpatient basis. Markers of efficacy comprise thyroid
function, thyroid scintigraphy and sonography including change in nodular volume.
Complete cure- fined as normalization of serum TSH and scintigraphic reactivation of

extranodular tissue is achieved in 68-100% of solitary hot nodules.
Partial cure – defined as detectable serum TSH and partial reactivation of extra-nodular tissue,
one of the limitations is clearly the need of repeat ethanol injection to achieve complete cure.
Side effects-
 Radiating pain = 90%
 Hyperpyrexia = 08%
 Transient dysphonia = 05%
 Neck hematoma = 4%
 Thrombosis of ipsilateral jugular vein.
 Hypothyroidism & fibrosis are rare.
PEIT seems most effective in small nodules and still require multiple injections and introduction
into routine use cannot be recommended until comparative randomized studies testing PEIT
against standard therapy have been undertaken.
75
Solitary cyst
The main concern is the fear of malignancy, although data indicate a lower frequency of
malignancy in a cystic than in a solid thyroid lesion but it is certainly high enough to warrant
considerable attention.
a. Simple aspiration –
It is the treatment of choice, smaller cysts (<2-3ml) are generally best left untreated. If larger
cyst, always perform aspiration and FNAB of any residual nodule.
b. T4 – therapy –
After aspiration put the patient on T4 suppression therapy. It reduces the chances of
recurrence.
c. Surgery
Surgical removal should be considered if large cyst >3cm and recur after aspiration. because
>10% of these lesion are reported to harbour thyroid cancer despite a benign FNAB.
d. Other treatment-
 PEIT
 Aspiration and injection of sclerosing agents i.e. tetracycline hydrochloride.
Side effect of ethanol injection is mild and transient and pain is less pronounced then that
described after injection in solid structure.
PEIT should still be regarded as an experimental treatment and be performed only by skilled
operators.
Table:- Treatment options in nontoxic solitary thyroid nodules:

Advantages Disadvantages
Surgery Nodule ablation Complete relief Inpatient
of symptoms Definite High cost
histological diagnosis Surgical risk
Vocal cord paralysis: ~%
Hypoparathyroidism: <1%
Hypothyroidism: 1%
Ethanol injection Outpatient Relatively low cost Repeat injections needed
No hypothyroidism Low efficacy in larger nodules (>15ml)
Operator dependency
Painful, causing reduced patient compliance
Transient dysphonia: 1-2%
Thyrotoxicosis (autoimmune response): ~1%
Cytological/histological interpretation impeded
in treated nodules
131
I Outpatient Contraceptives needed in fertile women
Low cost Gradual reduction of the nodule
Few subjective side effects Hypothyroidism: 10% within 5 yr
Nodule reduction: 45% within Radiation thyroiditis: 1-2%
2yr Autoimmune response: <1%
Long-term cancer risk unknown
L-
T4 Outpatient Low efficacy
Low cost Lifelong treatment
Nodule growth slowed Re-growth after cessation
Prevents in part new nodule Adverse effects (bone, heart)
formation Not feasible when TSH is suppressed
76
Management of Well Differentiated Thyroid Cancer
Dr. S.K.Mishra, P.V.Pradeep
Goals of initial therapy of differentiated thyroid cancer 1
– To remove the primary tumor and involved cervical lymph nodes

– To minimize treatment and disease-related morbidity
– To permit accurate staging of the disease
– To facilitate postoperative treatment with radioactive iodine, where appropriate
– To permit accurate long-term surveillance for disease recurrence
– To minimize the risk of disease recurrence and metastatic spread
Extent of pre operative staging in Well differentiated thyroid cancer (WDTC):
• Neck USG recommended in all patients with FNA proven DTC

• Cervical lymphadenopathy seen in 20-50% 2 cases, Micro-metastasis in 90% 3
• Detection of metastasis in CL nodes (FNA/ Frozen section) alters the management
strategy
• Routine preoperative use of other imaging studies (CT,MRI, PET) is not recommended 1
• Indicated only in selected cases (local invasion, retrosternal extension)
• Pre operative Thyroglobulin(Tg) measurement – not recommended 1
Surgery in WDTC
• Indications for Total Thyroidectomy 1,4

• Primary Tumor > 1-1.5cm
• Presence of contra lateral thyroid nodules
• Regional/ distant metastasis
• Previous history of head & neck irradiation
• First degree relative with WDTC
• Age > 45 yrs (Higher rates of recurrence in this group)
Advantages of Total Thyroidectomy 5
• Radioactive iodine and Tg can be used to follow up these patients

• Upto 85% of PTC have foci in the other lobe
• Upto 7% develop recurrence in the opposite lobe, 50% of these patients die
• Recurrence rate is lower in patients undergoing Total thyroidectomy
• Risk of dedifferentiation to anaplastic carcinoma is reduced
• Re-operative surgeries carry slightly higher complication rates
Indications for Hemithyroidectomy 1,4
– < 1cm solitary WDTC

– No evidence of nodal/ distant metastasis
– No H/O previous neck irradiation
– No family H/O WDTC in any of the first degree relatives
It has been shown that hemithyroidectomy in the above mentioned group of patients have excellent
results. Even though the local recurrence rates are slightly higher, it does not influence the overall
survival of the patient 6,7.
Indications for completion thyroidectomy:
77
• Completion thyroidectomy should be offered to those patients for whom a near-total or total
thyroidectomy would have been recommended had the diagnosis been available before the
initial surgery 1,4
• Radioactive iodine ablation of the remnant lobe in lieu of completion thyroidectomy is not
recommended 1,4
Extent of LN dissection- Central compartment
• Routine central-compartment (level VI) neck dissection recommended for patients with PTC,
however Central node dissection (CCLND) not necessary for follicular thyroid cancer. 1,4 It
has been shown that the death rate improves to 1.6% in patients who had CCLND vs 8.4-
11.1% in those who did not 8. The Serum thyroglobulin (Tg) was lower in pts who underwent
CCLND (p=0.02)
Current status of CCLND 8:
• Systematic compartment-oriented CLND decreases recurrence of PTC (levels IV and V data) and
improves disease-specific survival (grade C recommendation)
• Significantly reduce levels of serum thyroglobulin (level IV data)
• Slightly higher rate of permanent hypoparathyroidism and nerve injury when CLND is performed
with total thyroidectomy
• Reoperation in the central neck compartment increases the risk of hypoparathyroidism and nerve
injury compared with total thyroidectomy with or without CLND
• Can be applied to patients under the care of experienced endocrine surgeons
Lateral compartment dissection- Therapeutic 1
• All patients with biopsy proven cervical lymph node metastasis detected clinically or by
imaging
– Level 2-5 to be dissected ( Functional compartmental en bloc dissection is preferred)
Lateral compartment dissection- Prophylactic
• Prominent scoring systems such as EORTC, AMES, MACIS, and AGES do not regard node
metastasis as a prognostic indicator, hence, in Europe and the United States prophylactic
lymph node dissection is not done, however it‘s widely practiced by Japanese endocrine
surgeons since use of RAI is restricted by Japanese law. Prophylactic modified radical neck
dissection improves the prognosis of in a subset of patients having tumors with extra-thyroid
extension as well as females over 60 years old 9
Role of post operative staging system
• AJCC/UICC staging recommended for all patients with differentiated thyroid cancer since this
is needed in predicting disease mortality and is required for cancer registries
78
Role of post operative remnant ablation
Indications 1,4
• Stage III and IV disease
• All patients with stage II disease younger than age 45 years
• Most patients with stage II disease 45 years or older
• Selected patients with stage I disease
» especially those with multifocal disease, nodal metastases,
extra-thyroidal or vascular invasion, and/or more aggressive
histologies
Protocol of thyroid hormone withdrawal for remnant ablation
• Aim:
– Achieve TSH of more than 30 mU/L
• Single-dose exogenous rTSH results in TSH levels between 51–82 mU/L
• Endogenous TSH elevation can be achieved by
• Stopping levothyroxine (LT4) and switching to levo-triiodothyronine (LT3) for
2–4 weeks followed by withdrawal of triiodothyronine (T3) for 2 weeks
• Discontinuation of LT4 for 3 weeks without use of T3
• rTSH stimulation can be used for remnant ablation (Not approved in US)
Role of post operative diagnostic RAIU scan
• Indication:
– When the extent of thyroid remnant cannot be assessed from the surgical report/
USG
– If the result is likely to alter the subsequent management
– If the result is likely to alter the dose of RAI treatment
• If used, low dose I 131 (1-3mCi)/ I123 scan recommended
– Low iodine diet (50microgram/day for 1-2 weeks) is recommended prior to scan
• Post therapy scan:
• Detects additional foci in 10-26% cases, alters the stage in 10%
• Done 1 week post radio-iodine therapy
Role of TSH suppression therapy 4:
• Mechanism of action:
• Decreases the expression of thyroid specific proteins
• Decreases the rate of cell growth
• High risk pts:
• Keep TSH < 0.1mIU/L
• After remission continue suppressive therapy x 3-5 yrs
• Low risk patients
• TSH= 0.1-0.5 mIU/L
• After remission keep it between 0.5-1mIU/mL
Role of adjuvant chemotherapy and radiotherapy 1,4:
Adjunctive external beam irradiation is indicated in grossly visible extra thyroidal extension, in whom
further surgery/ radio-iodine will be in effective. There is no role for routine adjunctive
chemotherapy.
79
Risk group stratification in WDTC:
• This is to distinguish between high risk and low risk patients

• Less aggressive strategy can be adopted for low risk group
• Objective of risk stratification:
• To determine the extent of initial surgery
• To decide on radio-iodine therapy
• Decide on the degree of TSH suppression
• Decide on the follow up protocol
ATA & European consensus 2006 1,4 : High risk patients comprise of the following:
• Primary tumor >1–1.5 cm

• Contra lateral thyroid nodules
• Regional or distant metastases
• Personal history of radiation therapy to the head and neck
• First-degree family history of differentiated thyroid cancer
• Older age (>45yrs): Higher rates of local recurrences
AMES, AGES, MACIS, TNM are other scoring systems used to differentiate high and low risk patients
WDTC: Long term management
Patients are followed up with clinical examination, USG neck and estimation of serum Tg.
• Neck USG
• Detects lymph nodes as small as 2-3 mm. All LN > 5mm investigate-guided
FNA and Tg in aspirate
• To be performed periodically (6monthly)
• Serum Tg
• Anti Tg antibodies to be simultaneously assayed, False-ve S Tg if Anti Tg Ab
are +ve (IRMA)
• Measured with pt on thyroxine (in low risk), off thyroxine in high risk group
every 6 months
• Unstimulated or stimulated Tg > 2ng/mL that increase over time represents
recurrent disease
The algorithm to be followed during the follow up is shown in Fig 1.
Role of Dx-WBS in the long term follow up 1,4
• Not indicated
• In low risk pts with –ve USG neck and undetectable Tg
• Indicated
• In high risk patients 6 months after remnant ablation
• Subsequently indicated if Tg becomes +ve in the follow up
Protocol for long term TSH suppression

• Pts with persistent disease
• TSH to be kept < 0.1mIU/mL
• High risk patient , clinically free of disease
• TSH suppression x5yrs (<0.1mIU/mL)
• Subsequently TSH to be kept between 0.1-0.5mIU/mL
• Low risk pt free of disease
• TSH between 0.3-2mIU/mL
80
PET scan in follow up
• Fluorine 18 FDG, 18F (DOPA) and 124 I PET are the three radiopharmaceuticals used
• Indication 10:
– Tg +ve , WBS –ve patient
– Tg –ve with suspicious metastasis
• Sensitivity of 75% and specificity of 90% 11
Management of metastatic disease
• Persistent/Recurrent disease in the neck:

• Complete ipsilateral neck dissection
• Invasion of upper aero-digestive track:
• Surgery + RI ablation/ or external RT
• Pulmonary Metastasis:
• Micrometastasis: Radio-iodine therapy (100-300mCi)
• Radio-avid macronodular metastasis: Radio iodine therapy
– Non radio avid pulmonary metastasis
• Insufficient data for specific recommendation
• Single macronodular lesion or multiple lesions in the same lobe: Surgical
Excision*
• Bone metastasis:
– Relatively insensitive to I131 therapy.
– Remission rate: 7-20% 12
– Single localized metastasis: Surgical excision 13
– Large metastasis not resectable: Debulking can help in later ablation 14.
• Painful Bone metastasis:
• Radio iodine, Ext RT, Intra arterial embolization, Radio pharmaceuticals like
Strontium 89, Simarium 153, IV bisphosphonates
Metastatic disease-Chemotherapy
• Response rates to alkylating agents 10-15%. (5FU, Methotrexate)

• Response rate to Bleomycin and Adriamycin 20-33%.
• Indicated in
– Symptomatic & advancing tumors, not responding to Radio-iodine
– Not amenable to external RT
Metastatic disease-Radiotherapy 15,16
• Painful osseous metastasis can be palliated

• Bone mets not amenable to surgery
– Base of skull, vertebral column.
• No significant role apart from external RT for gross residual disease in neck
Conclusion:
• Adequate surgery is the mainstay initial treatment of WDTC

• Adjuvant therapy with radio-iodine is needed in high risk group
• TSH suppression is to be tailored as per the risk category
• Long term follow up is with clinical exam, USG neck and Tg, RAIU scan only in selected
cases
• Has good long term prognosis especially low risk group
81
Fig 1:
References:
1. Cooper et al. American Thyroid Association Guidelines, Thyroid 2006;16 (2):1-33

2. Grebe SK et al. Surg Oncol Clin North Am 1996 5:43–63
3. Arturi F et al. J Clin Endocrinol Metab 1997, 82:1638–1641
4. Pacini et al European consensus for management of WDTC, Eur J Endocrinology 2006;154: 787-803
5. Dackiw et al. Surg Clin N Am 2004; 84: 817-832
6. Shaha et al Ann Surg Oncol.1997.4(4):328-333
7. Hay et al Surgery 1998;124: 958-966
8. White et al. World J Surg 2007,31:895-904
9. Noguchi S et al. Arch Surg 1998;133:276–280
10. N Khan , Oriuchi et al The British Journal of Radiology. 76(2003) 690-695)
11. Fecine E. Eur J Endocrinol 1998; 138: 492-496
12. Eustatia-Rutten et al, JCEM 88(7)3184-89, July 2003.
13. Schlumberger, F Pacini. Thyroid Tumors: Chapter 9, 167-180: 1999
14. Leslie Degroot , Textbook of Endocrinology. 4th edition 2001 : 1560-62.
15. OConnell et al. European Journal of Cancer 1994;30A(6): 733-39
16. WJ Simpson et al. Int J Radiation Oncology Biol. Phys. 1998;14:1063-1075
82
Thyrotoxicosis
Prof. M. Chandrasekaran
Thyrotoxicosis is a condition where excessive thyroxine is circulating in the system producing a
symptom complex (tachycardia, tremors, palpitation, profuse sweating, voracious appetite and loss of
weight) due to its effect on the end organs. Though Thyrotoxicosis denotes elevated FT3 & FT4,
rarely patients might present with isolated T3 toxicosis.
Excessive thyroxine could be the result of (1) increased production by the gland (2) increased
liberation of the stored hormone from the gland (3) excessive intake of oral thyroxine or (4) excessive
production of thyroxine by an ectopic thyroid tissue.
Common causes for increased production

1. Graves‘ disease
2. Multinodular goiter with Toxicity
3. Toxic Nodule
Rare causes for increased production

1. Pituitary adenoma producing excessive TSH
2. Hydatiform mole ( HCG behaves like TSH )
3. Struma Ovarii (ectopic production of thyroxine)
4. Jod-Basedow phenomenon
Thyrotoxicosis without Hyperthyroidism

1.Toxic phase of thyroiditis
2. Excessive intake of thyroid hormone
In all cases of toxicity due to increased production, RAIU would be elevated along with elevated
FT3 & FT4. TSH would be suppressed in all cases except in pituitary adenoma.
Think of Graves‘ disease when the patient presents with

1. Exophthalmos
2. Diffuse goiter preceded by symptoms of toxicity
3. Positive Antithyroglobulin antibody titre
Graves‘ disease is an immunological disorder. It has three components. They are

1. Ophthalmopathy
2. Thyrotoxicosis and
3. Infiltrative dermopathy.
Graves‘ disease is a self limiting disease and it usually gets burnt out over a period of 2 years. Hence,
surgery on thyroid is not mandatory to control the toxicity. The only absolute indication for surgery in
Graves‘ disease is the coexistence of a thyroid nodule whose nature is uncertain and excision is
required to exclude malignancy. Commonly used antithyroid drugs are carbimazole and beta blocker.
Carbimazole prevents the production of thyroxine whereas beta blocker prevents the action of
thyroxine on the end organs. Both carbimazole and beta blocker will cross the placental barrier and
hence, they should be used with caution in antenatal patients.
Treatment for Graves‘ disease, in the order of preference, is given below:
1. Medical treatment
2. Radio iodine treatment (to be used with caution
in patients who are in the reproducing age group)
3. Surgery-Near total thyroidectomy
Ophthalmopathy:
Antibodies produced against the orbital autoantigen stimulates the retro orbital fibroblasts and they in
turn produce collagen and glycosaminoglycans. Collagen produces muscle fibrosis.
Glycosaminoglycans traps water and produces muscle oedema. This complex mechanism results in
83
periorbital oedema, diplopia, proptosis and if severe results in loss of vision due to optic nerve
compression.
Treatment of ophthalmopathy:
Other than the anti thyroid drugs which have the immune-modulatory effect, following treatment can
also be given.
1. High dose of prednisolone

2. Orbital radiotherapy
3. Cyclosporin A
4. Orbital decompression
Multinodular goiter with Toxicity:
Multinodular goiter with Toxicity is not an immunological disorder. Here the thyroid gland goes out of
the control of pituitary (Hypothalamo pituitary thyroid axis is not intact) and hence, the thyroid
produces excessive thyroxine. Though it was thought that the inter nodular areas alone are
responsible for the synthesis of thyroxine it has been proved beyond doubt that the nodules can also
synthesis thyroxine. The ideal treatment for multinodular goiter with toxicity is Near total thyroidectomy
after controlling the toxicity. Partial thyroidectomy should never be done since a recurrence can come
from the leftover pathological thyroid gland.
Toxic Nodule:
A hyperfunctioning solitary nodule which goes out of the control of pituitary would always produce
excessive thyroxine resulting in the symptom complex of thyrotoxicosis. In all these cases the
functioning thyroid nodule alone would be seen in a radio iodine scan and hence, the name ―Hot‖
nodule. The ideal treatment for this condition is a Hemithyroidectomy after controlling the toxicity.
Pituitary Adenoma:
An adenoma of the pituitary, producing excessive TSH, would act on the thyroid gland producing
secondary hyperthyroidism resulting in thyrotoxicosis. Like all thyrotoxic patients, these patients
with pituitary adenoma would also have an elevated FT3, FT4 and RAIU but with an elevated TSH.
These patients should undergo excision of the pituitary adenoma through a transsphenoidal route.
Hydatiform mole:
HCG has the properties of TSH and hence patients with hydatiform mole would also present with
features of thyrotoxicosis. Treatment should be aimed at the primary problem and not at the thyroid.
Struma ovarii:
Struma ovarii is a condition where an ectopic thyroid tissue is found in a teratoma of the ovary. Rarely
this can be the cause for excessive production of thyroxine. Excision of the ovarian tumour is the
treatment.
Jod –Basedow phenomenon:
People living in iodine deficiency areas would constantly be in a hypothyroid state. Hence, they
always have an elevated TSH and as a result develop a goiter. When iodine is given to them in large
doses, their thyroid gland would trap the iodine and produce excessive thyroxine resulting in
thyrotoxicosis. This phenomenon is called Jod –Basedow phenomenon.
Toxic phase of Thyroiditis:
In toxic phase of thyroiditis, thyroid follicle ruptures and liberates the hormone suddenly into the
system and those patients would present with elevated FT3, FT4 and suppressed TSH. This condition
should be differentiated from other causes of thyrotoxicosis since this toxicity is not due to increased
production of the thyroxine but due to increased liberation of the stored hormone in to the system.
Hence, these patients should not be treated with antithyroid tablets but only with beta blockers. RAIU
84
is the only investigation to differentiate toxic phase of thyroiditis from Hyperthyroidism
induced thyrotoxicosis. Here trapping is dependent on TSH and hence RAIU would be very low.
Positive Anti microsomal antibody titre (TPO) is the investigation to confirm autoimmune thyroiditis.
Iatrogenic Thyrotoxicosis:
This condition is due to excessive intake of thyroxine. In this condition also patient would present with
elevated FT3, FT4 and suppressed TSH. RAIU is the only investigation to confirm the diagnosis. Here
again trapping is dependent on TSH and hence RAIU would be negligible. This condition can be
differentiated from Toxic phase of thyroiditis by the negative Antimicrosomal antibody titre (TPO)
Thyrotoxic Storm:
Thyrotoxic storm is due to sudden release of excessive thyroxine in to the system. Common causes
for thyrotoxic storm are (1) damage to thyroid gland and (2) severe illness
Thyroid damage could be the result of surgery or Radio iodine treatment.
Damage to thyroid gland:
1. Inadequate preparation is the common cause for thyrotoxic storm following surgery.
2. Inadequate surgery is another cause for the storm.
Total thyroidectomy and Near total thyroidectomy may not result in thyrotoxic storm but a partial
thyroidectomy may produce a storm since the left over gland will liberate unlimited amount of stored
hormone into the system.
Treatment of thyrotoxic storm:
Following drugs are used in the management of thyrotoxic storm

1. Lugol‘s iodine
2. Large dose of Carbimazole
3. Betablocker
4. Steroids
5. Paracetamol
85
Current management of the complications of portal hypertension:
variceal bleeding and ascites
Nina Dib, Frédéric Oberti and Paul Calès
From the Department of Hepato-Gastroenterology, University Hospital, and HIFIH Laboratory,
Université d'Angers, Angers, France
Portal hypertension is one of the main consequences of cirrhosis. It can result in severe
complications, including bleeding of esophagogastric varices as well as spontaneous bacterial
peritonitis or hepatorenal syndrome as complications of ascites. We describe in brief the
pathophysiology of portal hypertension and review the current management of its complications, with
emphasis on variceal bleeding and ascites.
Pathophysiologic background
Portal hypertension
Portal hypertension is defined as an increase in blood pressure in the portal venous system. The
portal pressure is estimated indirectly by the hepatic venous pressure gradient — the gradient
between the wedged (or occluded) hepatic venous pressure and the free hepatic venous pressure. A
normal hepatic venous pressure gradient is less than 5 mm Hg.
In cirrhosis, portal hypertension results from the combination of increased intrahepatic vascular
resistance and increased blood flow through the portal venous system (Fig. 1). According to Ohm's
law, portal venous pressure (P) is the product of vascular resistance (R) and blood flow (Q) in the
portal bed (P = Q x R). Intrahepatic resistance increases in 2 ways: mechanical and dynamic. The
mechanical component stems from intrahepatic fibrosis development; various pathologic processes
are thought to contribute to increased intrahepatic resistance at the level of the hepatic
microcirculation (sinusoidal portal hypertension): architectural distortion of the liver due to fibrous
tissue,1 regenerative nodules,1 and collagen deposition in the space of Disse.2 The dynamic
component results from a vasoconstriction in portal venules secondary to active contraction of portal
and septal myofibroblasts, to activated hepatic stellates cells and to vascular smooth-muscle cells.3–5
Intrahepatic vascular tone is modulated by endogenous vasoconstrictors (e.g., norepinephrine,
endothelin-1, angiotensin II, leukotrienes and thromboxane A2) and enhanced by vasodilators (e.g.,
nitric oxide). In cirrhosis, increased intrahepatic vascular resistance results also from an imbalance
between vasodilators and vasoconstrictors.6
Fig. 1: Pathophysiology of portal hypertension
in cirrhosis. Portal hypertension results from
increased intrahepatic vascular resistance
and portal–splanchnic blood flow. In addition,
cirrhosis is characterized by splanchnic and
systemic arterial vasodilation. Splanchnic
arterial vasodilation leads to increased portal
blood flow and thus elevated portal
hypertension. An increased hepatic venous
pressure gradient leads to the formation of
portosystemic venous collaterals.
Esophagogastric varices represent the most
clinically important collaterals given their
associated high risk of bleeding. Treatment
consists of pharmacologic therapy to
decrease portal pressure, endoscopic
treatment of varices (band ligation or
sclerotherapy) to treat variceal bleeding, and
creation of a transjugular intrahepatic
portosystemic shunt (TIPS) to reduce portal
pressure if drug therapy and endoscopic
treatment fail. Photo by: Lianne Friesen and
Nicholas Woolridge
86
Portal hypertension is characterized by increased cardiac output and decreased systemic vascular
resistance,7 which results in a hyperdynamic circulatory state with splanchnic and systemic arterial
vasodilation. Splanchnic arterial vasodilation leads to increased portal blood flow, which in turn leads
to more severe portal hypertension. Splanchnic arterial vasodilation results from an excessive release
of endogenous vasodilators such as nitric oxide, glucagon and vasoactive intestinal peptide.
An increase in the portocaval pressure gradient leads to the formation of portosystemic venous
collaterals in an attempt to decompress the portal venous system. Esophageal varices, drained
predominantly by the azygos vein, are clinically the most important collaterals because of their
propensity to bleed. Esophageal varices can develop when the hepatic venous pressure gradient rises
above 10 mm Hg.8–10 All factors that increase portal hypertension can increase the risk of variceal
bleeding, including deterioration of liver disease,11 food intake,12,13 ethanol intake,14 circadian
rhythms,15 physical exercice16 and increased intra-abdominal pressure.17 Factors that alter the variceal
wall, such as ASA and other NSAIDs, could also increase the risk of bleeding.18,19 Bacterial infection
can promote initial and recurrent bleeding.20
Ascites and hepatorenal syndrome

In advanced cirrhosis, splanchnic arterial vasodilation promoted by portal hypertension is pronounced
and leads to the impairment of systemic and splanchnic circulation.21 Systemic vasodilation leads to
relative hypovolemia, with a decrease in effective blood volume and a fall in mean arterial pressure.
States of homeostasis and antinatriuresis are activated to maintain arterial pressure, which results in
sodium and fluid retention.21 In addition, a combination of portal hypertension and splanchnic arterial
vasodilation alters splanchnic microcirculation and intestinal permeability, facilitating the leakage of
fluid into the abdominal cavity.21 As cirrhosis progresses, the kidneys' ability to excrete sodium and
free water is impaired; sodium retention and ascites develop when the amount of sodium excreted is
less than the amount consumed.21 Decreased free water excretion leads to dilutional hyponatremia
and eventually to impaired renal perfusion and hepatorenal syndrome.21
Variceal bleeding
Variceal bleeding is a medical emergency associated with high rates of recurrence and death.22–25 Its
management is based on specific treatments, including pharmacologic therapy, endoscopic treatment
and antibiotic therapy.
Pharmacologic therapy
Vasopressin and its analogue terlipressin: Vasopressin is a potent splanchnic vasoconstrictor;
however, its use was abandoned 25 years ago in most countries because of its severe vascular side
effects. Terlipressin, a vasopressin analogue not currently licensed for use in Canada, has similar
effects,26 reducing the hepatic venous pressure gradient, variceal pressure and azygos blood flow.27,28
Terlipressin has been found to be superior to placebo in the control of variceal bleeding.29 It has also
been found to decrease renal vasoconstrictor system activity and improve renal function in patients
with hepatorenal syndrome.30–33 However, terlipressin can induce ischemic complications, particularly
in cases of severe hypovolemic shock,34 and it is contraindicated in patients with cardiovascular
disease (arterial disease with severe obstruction, cardiac insufficiency, arrhythmias, hypertension).
Somatostatin and its analogues octreotide and vapreotide: Somatostatin significantly reduces the
hepatic venous pressure gradient,35–37 variceal pressure38 and azygos blood flow;36 however, because
its hemodynamic effect is transient, continuous infusion is required.36 Four placebo-controlled studies
showed contrasting results. Somatostatin was more effective than placebo in controlling variceal
bleeding,39,40 but its effectiveness in reducing the need for transfusion41,42 and balloon tamponade41
remains unproven. Terlipressin appears to be as effective as somatostatin in the control of bleeding.29
Octreotide and vapreotide have a longer half-life than somatostatin and are useful in the management
of portal hypertension. Octreotide decreases the hepatic venous pressure gradient and azygos blood
flow43–46 but not variceal pressure.27,47 However, the effect of octreotide is transient43–46 and
controversial.48 It prevents the increase in hepatic blood flow after a meal,49 and it seems to be as
efficient as terlipressin in treating variceal bleeding and in improving the efficacy of endoscopic
therapy.50–52 Only one double-blind randomized controlled trial of octreotide has been published (in
brief) to date, and it showed that octreotide was not more effective than placebo in controlling and
preventing early recurrent variceal bleeding.53 In a randomized controlled trial, vapreotide, a long-
acting analogue of somatostatin not currently licensed for use in Canada, was administered before
87
endoscopic treatment and was found to result in fewer blood transfusions and better control of
bleeding than endoscopic treatment alone.54
No major toxic effects and practically no complications are associated with the use of somatostatin or
its analogues.
Endoscopic diagnosis and treatment

Endoscopy is useful in the diagnosis and treatment of bleeding esophagogastric varices. Three
endoscopic techniques are currently used: endoscopic band ligation, endoscopic sclerotherapy and
variceal obturation with glue.
Endoscopic band ligation: Currently, endoscopic band ligation is the first choice of endoscopic
treatment for esophagogastric varices. The procedure involves placing an elastic band on a varix,
which allows aspiration of the varix in a cylinder attached to an endoscope. A maximum of 5–8 elastic
bands should be used per session. Sessions should be performed every 2–3 weeks until the varices
have been obliterated or have become so small that ligation is impossible.55 Complications of
endoscopic band ligation are fewer than those with endoscopic sclerotherapy. Generally, bleeding
from a post-ligation ulcer is moderate.56
Endoscopic sclerotherapy: There are several sclerosant agents (polidocanol, ethanolamine, ethanol,
tetradecyl sulfate and sodium morrhuate), and they provide similar results. The treatment involves
intravariceal or paravariceal injections of the sclerosant agent (total volume 10–30 mL per session)
every 1–3 weeks until the varices have been obliterated.56 Given that varices recur in 50%–70% of
cases,57 surveillance endoscopy every 3–6 months is required.57,58 Frequent complications of
endoscopic sclerotherapy are retrosternal pain, dysphagia and postsclerotherapy bleeding ulcers.
More severe complications, such as esophageal perforation or stricture, have been reported.56
Variceal occlusion with glue: This treatment is especially useful in patients who have had gastric or
gastroesophageal variceal bleeding. It consists of embolization of varices by injecting them with the
tissue adhesive N-butyl-2-cyanoacrylate; the adhesive polymerizes in contact with blood. One millilitre
of adhesive is injected at a time, with a maximum of 3 injections per session. The most serious risk
associated with this procedure is embolization of the lung, spleen or brain.59
Transjugular intrahepatic portosystemic shunt

Percutaneous creation of a transjugular intrahepatic portosystemic shunt (TIPS) through a jugular
route connects the hepatic and portal veins in the liver. The goal is to reduce portal pressure and thus
prevent variceal bleeding.60 TIPS diverts portal blood flow from the liver, but it increases the risk of
encephalopathy.61–63 In most cases encephalopathy responds to standard therapy, but in some cases
the calibre of the shunt has to be reduced;60 rarely, when encephalopathy does not respond to
treatment (in 5% of cases) the shunt should be occluded.60 Thrombosis and stenosis are other
complications that can cause TIPS dysfunction.60 Recently, it has been reported that the use of a
polytetrafluoroethylene-covered stent decreases the rate of shunt dysfunction.64 The putative
increased risk of hepatocellular carcinoma remains to be clarified.
Other treatment options
Balloon tamponade: In cases of massive or uncontrolled bleeding, balloon tamponade provides a

"bridge" to definitive treatment with TIPS or portosystemic surgical shunt.55,65 The most frequently
used balloon is the 4-lumen modified Sengstaken–Blakemore tube, which employs a gastric and
esophageal balloon.56 In cases of bleeding gastric varices, use of the Linton–Nachlas tube with a large
gastric balloon is recommended.56
Portosystemic surgical shunt: Its usefulness has dramatically decreased since the advent of TIPS.
Moreover, the procedure requires an experienced surgeon. In cases of refractory bleeding and when
TIPS is technically impossible, creation of a nonselective portosystemic shunt may be suitable in
patients with cirrhosis provided that the liver dysfunction is not too severe (Child–Pugh class A or B,
Appendix 1).
88
Practical management
Fig. 4: Algorithm for the primary prophylaxis of

variceal bleeding in cirrhosis.
55
Variceal bleeding should be managed in an intensive care unit. Treatment should include nonspecific therapy,
such as blood volume replacement and antibiotic prophylaxis, as well as specific treatments, such as
pharmacologic therapy and endoscopic treatment (Box 1, Fig. 2).
Nonspecific treatment
Nonspecific treatment aims to correct hypovolemia and to prevent complications. Blood volume
replacement should be done cautiously using concentrated erythrocytes to obtain a hemoglobin level
of about 70–80 g/L.55,65 Overtransfusion should be avoided given the risk of increased portal
pressure37,66,67 and continued or recurrent bleeding.68 Plasma expanders are used to maintain
hemodynamic stability and renal perfusion pressure.55,65 Either a crystalloid (isotonic saline solution)
or colloid solution can be used, but a crystalloid solution is preferred because it is harmless.55
Infection occurs in 25%–50% of patients with cirrhosis and gastrointestinal bleeding.69 Failure to
control bleeding and rates of death are increased in infected patients.69,70 The early administration of
antibiotic prophylaxis will benefit all patients with variceal bleeding and improve survival.55,65,71,72 One
recommended protocol is oral administration of norfloxacin (400 mg twice daily for 7 days).55,73
89
The routine use of a nasogastric tube is not recommended. Patients with encephalopathy should be
given lactulose;65 however, insufficient information exists to recommend its use in the prevention of
hepatic encephalopathy.55,65
Specific treatment
Intravenous therapy with a vasoactive drug should be started as soon as possible following hospital
admission, before diagnostic endoscopy, and maintained for 2–5 days (Box 1).54,55,65,74 Vasopressin is
not recommended because of its deleterious side effects.
Endoscopy should be performed within 12 hours after hospital admission on an empty stomach, which
can be achieved by either intravenous injection of erythromycin (250 mg begun 30–60 minutes before
endoscopy) or lavage through a nasogastric tube.55,65 Endoscopy is useful in confirming the source of
bleeding and allowing hemostatic treatment. Either endoscopic band ligation or endoscopic
sclerotherapy may be used.55,65 However, endoscopic band ligation is the recommended first-line
treatment.65 In patients who have bled from gastric or gastroesophageal varices, endoscopic
obliteration with the tissue adhesive N-butyl-2-cyanoacrylate should be performed.65 However,
endoscopic band ligation is also possible to treat gastroesophageal varices.
If combined vasoactive and endoscopic therapy fails, a second attempt at endoscopic therapy is
justified if the bleeding is mild and the prognosis not compromised.55,65,75 TIPS is a second-line
treatment option.65 Balloon tamponade can be used as a "bridge" in cases of massive bleeding.55,65 If
bleeding persists or compromises prognosis, TIPS or surgical shunt creation should be offered as a
rescue therapy.55,65
Esophagogastric varices
At present, there is no satisfactory nonendoscopic indicator to detect the presence of esophagogastric

varices.65,76 Endoscopic screening is the best technique.76,77 The goal of management is to prevent
variceal bleeding. This is achieved in 3 ways: by preventing the development of varices (preprimary
prophylaxis), by preventing a first variceal bleeding episode once varices have developed (primary
prophylaxis) and by preventing recurrent bleeding (secondary prophylaxis) (Fig. 3).
Fig. 3: Prophylaxis of variceal bleeding in cirrhosis. Preprimary prophylaxis is aimed at preventing

esophagogastric varices (EV) from developing. The goal of primary prophylaxis is to prevent a first variceal
bleeding episode once medium or large varices have formed. Secondary prophylaxis is used to prevent recurrent
variceal bleeding. Photo by: Lianne Friesen and Nicholas Woolridge
Pharmacologic therapy
Pharmacologic therapy is used to control and prevent variceal bleeding. The 2 classes of drugs used
are ß-blockers and nitrates.
ß-Blockers: ß-Blockers lower portal pressure by reducing portal blood flow. The blood flow is reduced
as a consequence of decreased cardiac output (ß1 receptor blockade) and arteriolar splanchnic
vasoconstriction by an unopposed -vasoconstrictive effect (ß2 receptor blockade).78 Nonselective ß-
90
blockers such as propranolol, nadolol and timolol are more effective than selective ß1-blockers in
reducing the hepatic venous pressure gradient.79,80 The median reduction of the gradient by
nonselective ß-blockers is about 15%.79,81–84 Nonselective ß-blockers reduce variceal pressure85 and
azygos blood flow86–88 even in patients who do not exhibit a marked decrease in the hepatic venous
pressure gradient (propranolol "nonresponders").87,89 Propranolol has been found to prevent increases
in portal pressure related to physical exercise in patients with cirrhosis90 and to decrease the rate of
bacterial translocation.91 It has also been found to reduce postprandial peak in portal pressure;92
however, this effect with long-term use was not confirmed in 2 recent trials.93,94
It has been suggested that the hepatic venous pressure gradient could be measured to evaluate the
efficiency of ß-blocker treatment.95 Several studies have shown that variceal bleeding does not occur if
the gradient is reduced to below 12 mm Hg81,96 or that bleeding occurs at a low rate if the gradient is
reduced by at least 20% of the basal value.96–99 However, the prognostic value of the hepatic venous
pressure gradient on survival is still controversial.100,101 Besides, the measurement of the gradient is
invasive and not cost-effective; its use is not recommended in clinical practice and is limited to
selected hospitals.76
Nitrates: The mechanism of the vasodilatory effects of nitrates — vascular tone reduction and
decreased intrahepatic resistance — is not completely understood. It likely involves nitric oxide
release. Isosorbide mononitrate is the only nitrate that has been tested in randomized trials. It has
been found to reduce the hepatic venous pressure gradient102 and to enhance the splanchnic
hemodynamic effect of propranolol.103 However, its systemic effects can lead to deleterious arterial
hypotension. Nitrates are used in association with vasopressin or its analogue terlipressin.
Preprimary prophylaxis
Three clinical trials have studied this issue, but the results are not concordant.104–106 According to a
statement from the Baveno international consensus conference, the use of ß-blocker therapy is not
recommended for preprimary prophylaxis.65
Primary prophylaxis
Endoscopic screening for the presence of esophagogastric varices should be done in all patients
after the diagnosis of cirrhosis (Box 2).55,65 Screening should be repeated every 3 years in patients
without varices and every 2 years in those with small varices (Fig. 4).55 Endoscopic follow-up should
then relate to the initial size of detected varices. In case of large varices, endoscopic follow-up is not
necessary, and primary prophylaxis with a nonselective ß-blocker (propranolol or nadolol) should be
started.55 Endoscopic band ligation is useful in preventing variceal bleeding in patients with medium or
91
large varices; however, its long-term benefit requires further research,65 and it is not currently
proposed for use in primary prophylaxis unless the patient has contraindications to or side effects from
nonselective ß-blocker therapy.
Fig. 4: Algorithm for the primary prophylaxis of variceal bleeding in cirrhosis.
Therapy with a nonselective ß-blocker is effective in reducing the risk of a first variceal bleeding
episode in patients with medium or large varices.65,107–111 Conventional treatment consists of
administering the drug orally twice daily and titrating the dose according to the patient's tolerance and
to the treatment objectives based on heart rate response.112,113 However, results of a
pharmacodynamic study suggested that a single daily dose of long-acting propanolol is sufficient114
(80 or 160 mg, depending on the available dose in each country115). In all cases, doses should be
adjusted to obtain a 20%–25% reduction in heart rate or a heart rate of less than 55 beats/min.55
Propranolol is effective for a few days in cirrhotic patients after the last dose is administered.114 ß-
Blocker therapy should be maintained indefinitely,55 since late withdrawal can be deleterious on
survival despite the lack of an increased risk of bleeding.116 In patients who do not tolerate or have
contraindications to ß-blocker therapy, endoscopic band ligation is recommended55,65 (Fig. 4). Nitrates
(isosorbide mononitrate) are ineffective in preventing variceal bleeding if used alone,117,118 and their
use in primary prophylaxis is not recommended.55,65
Secondary prophylaxis
All patients who survive a variceal bleeding episode should receive treatment to prevent recurrent
episodes. As a first-line treatment, both pharmacologic and endoscopic treatments can be used to
prevent a recurrence. Pharmacologic therapy includes use of a nonselective ß-blocker.111,119–122
92
Although it has been proposed,123 combined treatment with isosorbide mononitrate and propranolol is
not recommended.55,65
Eradication of varices by endoscopic procedures is also effective in preventing recurrent variceal

bleeding. Only endoscopic sclerotherapy has been compared with placebo, and it was associated with
a significant reduction in recurrent bleeding and mortality.56,124 Endoscopic band ligation is currently
preferable to endoscopic sclerotherapy,55 since it has been found to be more effective in reducing the
risk of recurrent variceal bleeding and the incidence of variceal stricture.125–127 Combined therapy with
the 2 endoscopic procedures does not appear to be more effective than endoscopic band ligation
alone.128 However, endoscopic sclerotherapy may be effective in preventing the recurrence of varices
when endoscopic band ligation is no longer feasible. One trial of endoscopic band ligation with and
without therapy with nadolol and sucralfate for secondary prophylaxis showed reduced rates of
recurrent variceal bleeding in the group given the combined therapy.129 Such a beneficial effect was
not confirmed for combined therapy with endoscopic sclerotherapy and nonselective ß-blockers.130,131
If secondary prophylaxis with a nonselective ß-blocker or endoscopic band ligation, or both, fails to
prevent variceal bleeding, rescue therapies should be considered. Both TIPS and surgical shunt
creation are effective in preventing recurrent variceal bleeding.125 TIPS is more effective than
endoscopic treatment,132 and surgical shunt creation is more effective than endoscopic
sclerotherapy;133 however, neither TIPS nor surgical shunt creation has been found to improve
survival, and both are associated with a high risk of encephalopathy.132,133
The 2 consensus statements on portal hypertension55,65 have established recommendations on

prophylaxis status before variceal bleeding (Box 3). In patients who have not received previous
primary prophylaxis, therapy with a nonselective ß-blocker or endoscopic band ligation, or both, can
be used. If primary prophylaxis with a ß-blocker at an appropriate dose fails, the ß-blocker therapy
should not be continued alone and endoscopic band ligation should be performed. If the ß-blocker
dose is not found to be appropriate, either changing it to an optimal dose or performing endoscopic
band ligation is possible. If endoscopic band ligation fails as primary prophylaxis, TIPS is the next
option. Liver transplantation should be considered in all cases, particularly in patients with severe
cirrhosis (Child–Pugh class B or C).
93
Ascites and its complications
Ascites occurs in cases of advanced cirrhosis and severe portal hypertension. The ultimate
complications of ascites are refractory ascites, hepatorenal syndrome and spontaneous bacterial
peritonitis.
Uncomplicated ascites
All patients with ascites should undergo an evaluation of ascitic fluid content to rule out spontaneous
bacterial peritonitis.134,135 The evaluation should include cell count, bacterial culture in blood culture
medium, measurement of protein concentration and cytologic examination in cases of suspected
malignant ascites.134,135 The use of leukocyte reagent strips has been recently proposed for the early
detection of leukocytes in ascites and spontaneous bacterial peritonitis.136–139
For subclinical ascites detectable only by ultrasonography, no specific treatment is necessary.135

However, a reduction in daily sodium intake (to 90 mmol/d) is recommended.
In cases of moderate ascites, renal function is usually preserved and treatment can be administered
on an outpatient basis.134 Moderate dietary sodium restriction (90 mmol of sodium per day) should be
imposed.135 Spironolactone, an anti-mineralocorticoid, is the drug of choice at the onset of treatment
because it promotes better natriuresis more often than loop diuretics.140 It blocks the aldosterone-
dependent exchange of sodium in the distal and collecting renal tubules, thus increasing the excretion
of sodium and water.141 The initial dose is about 100–200 mg/d.134,135 About 75% of patients respond
to treatment after only a few days.135 Side effects of spironolactone are gynecomastia, metabolic
acidosis, hyperkalemia and renal impairment.135 In the presence of edema, treatment with furosemide
(20–40 mg/d) may be added for a few days to increase natriuresis.134,135 Loop diuretics act by
increasing sodium excretion in the proximal tubules. In cirrhosis, the effect of loop diuretic
monotherapy is limited and therefore is more commonly used as an adjunct to spironolactone
therapy.135 The side effects of furosemide include hypokalemia, metabolic hypochloremic alkalosis,
hyponatremia, hypovolemia and related renal dysfunction.135 Amiloride (5–10 mg/d) may be used
when spironolactone is contraindicated or if side effects such as gynecomastia occur.134,135 It also acts
in the distal tubule.135 Diuretic therapy should be monitored by measuring the patient's weight and
levels of serum electrolytes, urea and creatinine daily.135 Maximum weight loss should not exceed 500
g/d in patients without peripheral edema and 1000 g/d in those with it.135 If the therapeutic effect is
insufficient, urinary sodium excretion should be determined to identify nonresponsive patients
(characterized by a urinary sodium excretion below 30 mmol/d).135
Patients with severe ascites will have marked abdominal discomfort. In such cases, higher diuretic
doses are needed (i.e., up to 400 mg of spironolactone and 160 mg of furosemide daily).134,135
However, in some patients, free-water excretion is impaired and severe hyponatremia may develop.134
Frequently, large-volume paracentesis should be done.135 Paracentesis should be routinely combined
with plasma volume expansion. If the volume of ascites removed is less than 5 L, a synthetic plasma
substitute may be used.135,142 If more than 5 L of ascitic fluid is removed, albumin should be given at a
dose of 8 g per litre of fluid removed.135
Refractory ascites develops in about 10% of cases.143 In such cases, liver transplantation should be
considered.55,135 In the meantime, therapeutic strategies can involve repeated large-volume
paracentesis and plasma volume expansion with albumin or TIPS.55,134,135 TIPS improves renal
function and sodium excretion60,144,145 and is more effective than paracentesis in removing ascites.61,63
TIPS has a mortality not significantly differrent from that associated with paracentesis.63 Nevertheless,
a recent meta-analysis has reported a tendency toward improved survival with TIPS.61
Hepatorenal syndrome
Hepatorenal syndrome is the most serious circulatory renal dysfunction in cirrhosis21 and is the most
severe complication of portal hypertension. It occurs in up to 10% of patients with ascites.146 The
syndrome is defined by a serum creatinine concentration greater than 1.5 mg/dL (> 133 µmol/L).134
Type 1 hepatorenal syndrome involves the rapid impairment of renal function, characterized by a
doubling of the initial serum creatinine concentration to more than 2.5 mg/dL (> 221 µmol/L) within 2
weeks.146 In type 2 hepatorenal syndrome, renal impairment is stable or progresses at a slower rate
than that in type 1.146
94
The ideal treatment of hepatorenal syndrome is liver transplantation.55 Besides transplantation,
vasoactive drug therapy in combination with albumin (20–40 g/d for 5–15 days) can be used.55,134 The
efficiency of terlipressin (0.5–1 mg intravenously every 4–12 hours) has been reported in several
uncontrolled trials.31–33 Therapy with norepinephrine (0.5–3.0 mg/h intravenously)147 or midodrine (7.5–
12.5 mg orally 3 times daily) in association with octreotide (100–200 µg subcutaneously 3 times
daily)148 has been suggested to improve hepatorenal syndrome, but its effectiveness remains to be
confirmed. TIPS has been found to be effective in the management of hepatorenal syndrome by
improving renal function, particularly in patients with a Child–Pugh score of 12 or less and a serum
bilirubin level below 85 µmol/L.149
Spontaneous bacterial peritonitis
Spontaneous bacterial peritonitis, an infection of the ascitic fluid, occurs in 10%–30% of patients with
ascites.73 All cases in which the neutrophil count is at least 250 x 106/L in ascitic fluid should be
treated empirically, since ascites culture yields negative results in about 40% of patients with
symptoms suggestive of spontaneous bacterial peritonitis.55,73 Empirical treatment should also be
started if leukocytes are detected in ascitic fluid at a significant level on reagent strips.136–139
Because most cases of peritonitis are due to gram-negative bacteria (e.g., Escherichia coli),134
therapy with a third-generation cephalosporin is the treatment of choice (cefotaxime 2–4 g/d,
intravenously, for 5 days).55,73 Alternative treatments include combination therapy with amoxicillin and
clavulinic acid (1 g and 0.125 g respectively, given intravenously or orally 3 times daily) or norfloxacin
(400 mg/d, orally) for 7 days.55,73 Antibiotic therapy should be used in conjunction with albumin infusion
(1.5 g/kg on day 1 and 1 g/kg on day 3)55 to prevent renal failure and death.150 Treatment efficacy
should be assessed by means of evaluating clinical symptoms and determining the neutrophil count in
ascitic fluid after 48 hours.55,73 If treatment fails, antibiotic therapy should be shifted toward a broader-
spectrum drug or to one adapted to the organism's antibiogram.55,73
Primary prophylaxis of spontaneous bacterial peritonitis with continuous oral norfloxacin therapy (400
mg/d) in hospital patients with cirrhosis who have a low ascitic protein concentration (< 10 g/L) is still
debated.55,73 The same treatment is recommended for secondary prophylaxis of spontaneous
bacterial peritonitis until the ascites resolves, a treatment option that is more easily accepted by
clinicians.55,73
Summary
Portal hypertension can lead to severe outcomes in patients with cirrhosis, including bleeding of esophagogastric
varices and complications of ascites.
Variceal bleeding is a clinical emergency and requires blood volume replacement, early vasoactive drug therapy,
prophylactic antibiotic treatment and endoscopic treatment. Prophylaxis of variceal bleeding involves the use of ß-
blocker therapy (first-line treatment in primary and secondary prophylaxis) and endoscopic treatment, especially band
ligation (second-line step in primary and first-line step in secondary prophylaxis).
Treatment of ascites includes diuretic therapy and dietary sodium reduction. Main complications of ascites are refractory
ascites, hepatorenal syndrome and spontaneous bacterial peritonitis. In refractory ascites, repeated large-volume
paracentesis (with volume expansion using albumin) and TIPS can be proposed. In hepatorenal syndrome, the most
serious complication of ascites, liver transplantation should be considered; vasoactive drug therapy in combination with
albumin infusion can be given in the meantime. All patients with ascites should be screened for spontaneous bacterial
peritonitis; if detected, treatment consists of antibiotics and albumin infusion to prevent hepatorenal syndrome.
95
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To view the article with Web enhancements, go to: http://www.medscape.com/viewarticle/506983
100
Is There Still a Role for Surgery in Bleeding Portal Hypertension?
J Michael Henderson; Yolanda Yang
Nat Clin Pract Gastroenterol Hepatol. 2005;2(6):246-247.
For centuries, gastrointestinal bleeding has been recognized as a major cause of morbidity and
mortality in patients with pathology of the portal circulation. By contrast, a fuller understanding of the
pathophysiology of portal hypertension and variceal hemorrhage has occurred only over the past
three decades. This has led to significant advances in therapies for the prevention and treatment of
bleeding in portal hypertension. As more-effective therapies evolve, the role of the surgeon may be
considered to be in question, or in evolution.
In the US, portal hypertension is most commonly caused by alcoholic cirrhosis, but it is increasingly
seen secondary to hepatitis C. Increased resistance in the portal vascular system can also occur for
many other reasons, such as portal-vein thrombosis, leading to portal hypertension and the risk of
variceal bleeding. The incidence of gastroesophageal varices in cirrhotic patients is ~50%, and
bleeding from them causes death in up to one-third of patients with cirrhosis. Without intervention,
only 50% of acute bleeding episodes achieve hemostasis, and the risk of early and late rebleeding is
extremely high.[1]
Early therapies for variceal bleeding were limited, and in the 1930s consisted of temporizing
measures, such as balloon tamponade and rigid endoscopic sclerotherapy. Portacaval and central
splenorenal shunts became popular in the 1940s, but the long-term results of these total shunts were
disappointing owing to a significant increase in hepatic encephalopathy and the risk of worsening liver
failure. The use of vasopressin and improvements in balloon tamponade followed in the 1950s.
The 1960s saw the introduction of new surgical approaches. The distal splenorenal shunt (DSRS)
was introduced, which selectively decompressed gastroesophageal varices while maintaining portal
perfusion to the liver. Liver transplantation, successfully achieved by Starzl in 1967, has become the
only therapeutic option to treat portal hypertension and address underlying liver disease
simultaneously. In the 1980s, treatment moved to endoscopic therapies, with flexible scopes allowing
sclerotherapy and then banding. This was soon followed by pharmacologic therapy with nonselective
β-blockade for the prevention of bleeding.
In the 1990s radiologists added to the useful treatment options for bleeding from portal hypertension,
with the development of the nonsurgical transjugular intrahepatic portosystemic shunt (TIPS).[2]
Treatment has evolved from surgery being the only option up through the 1970s to the wide range of
options now available. Surgery has not vanished in treating these patients, however, but its role has
changed.
Convention dictates that the term prophylaxis refers to preventing the first variceal bleed. There is a
plethora of data on prophylaxis via surgery, endoscopy, pharmacologic therapy and TIPS. The
difficulty of analyzing these data is compounded by the multiple treatment modalities, and the
heterogeneity of patient populations. The current treatment modality has emerged from multiple meta-
analyses, which support the use of β-blockade as the standard of care for primary prophylaxis in
nonselected patients with medium or large gastroesophageal varices identified by endoscopy.[3]
Endoscopic variceal ligation is probably also useful in prophylaxis, especially in patients who do not
tolerate pharmacologic therapy.[4] Endoscopic sclerotherapy has been associated with an increased
mortality and is not indicated for primary prophylaxis.[5] The risk of increased hepatic encephalopathy,
accelerated liver failure, or periprocedural complications with either TIPS or surgical shunts, means
that shunting procedures are not justified for prophylaxis.[1, 3]
Patients with acute bleeding are best managed by a team including critical-care physicians,
gastroenterologists, hepatologists, surgeons and interventional radiologists. During the acute episode,
being able to carry out basic resuscitation is paramount, although over-resuscitation should be
avoided. Endoscopic intervention with variceal banding in combination with pharmacotherapy, using
octreotide 50 µg/hr by continuous infusion, will control acute variceal bleeding in >80% of patients. For
the patient who continues to bleed actively, emergency TIPS is effective in stopping the bleeding.
101
Emphasis is on 'total' patient care, with airway protection, careful fluid management, antibiotics and
nutrition. Emergency surgical procedures are rarely indicated.
Patients with gastroesophageal varices who have had a bleeding episode should have elective
interventions to prevent rebleeding, with endoscopic banding of varices that have bled combined with
β-blockade. For the 20% of patients who rebleed despite this primary therapy, decompression might
be needed. The value of 'surgical rescue' was shown in the 1980s,[6] and this concept is still valid. The
question at present is whether decompression is best done surgically or with TIPS. Nontransplant
surgical data obtained in the past decade have promoted the use of DSRS, which works well for
patients with refractory bleeding who have well-preserved liver function. The role of total
portosystemic shunts has virtually vanished. Devascularization surgery is reserved for patients with no
surgical-shunt options. TIPS has, however, become widely used because of its ease of application.
Data indicate that TIPS has a high stenosis rate (>50%) requiring redilation, and up to a 30% rate of
'new' encephalopathy.[7] Two randomized trials addressed the relative efficacy of TIPS or surgical
shunt. The first of these compared TIPS with a partial (8 mm) portocaval shunt in an 'all comers'
population, of whom 50% were Child-Turcotte-Pugh class C.[8] The surgical shunt performed better for
control of bleeding, reduced the need for transplant, and improved overall shunt success rate,
although survival was not significantly different. The second study compared DSRS with TIPS in
Child-Turcotte-Pugh class A and B patients.[9] There was no significant difference in rebleeding rates
(6% after DSRS and 9% after TIPS), encephalopathy or survival, but TIPS patients required
significantly ( P < 0.001) more reinterventions (83% of patients). Has TIPS replaced the surgical
shunt? The jury is still out. Clearly there are trade-offs, and the decision to decompress varices should
still be made on an individual basis.
Clearly, the surgeon still plays a role in treating this group of patients, with liver transplant. It is end-
stage liver disease, rather than variceal bleeding, that dictates the need for such surgery, which treats
both portal hypertension and variceal bleeding with the additional advantage of restoring liver function.
Transplant is the ultimate 'shunt'! Not all patients are eligible, however, such as active alcoholics and
those with concomitant disease, and the specific post-transplant risks of immunosuppression and
infection must also be considered. Progress in this area continues to be made: eligibility criteria are
expanding, management evolving, and results improving.[10]
The role for surgery in bleeding portal hypertension has changed dramatically in the last few decades.
Although there remains some role for surgical shunts, this has been markedly reduced, calling in to
question the training of young surgeons. The use of liver transplantation as a treatment, however, has
continued to grow. In the emergent setting, surgery is rarely needed. In the elective setting, DSRS
provides excellent long-term results for patients with stable liver disease and good liver function. Many
patients are adequately treated with TIPS, but DSRS might be preferred for patients who cannot or
will not comply with the follow-up investigations and interventions that are required for TIPS to achieve
comparable long-term results to DSRS. Finally, liver transplant remains the ultimate treatment, which
both decompresses portal hypertension and addresses the underlying liver disease in eligible
candidates.
References
1. Comar KM and Sanyal AJ (2003) Portal hypertensive bleeding. Gastroenterol Clin North Am 32:1079-1105
2. Pagliaro L et al . (1992) Prevention of first bleeding in cirrhosis. A meta-analysis of randomized trials of
nonsurgical treatment. Ann Intern Med 117:59-70
3. Luca A et al . (1999) TIPS for prevention of recurrent bleeding in patients with cirrhosis: meta-analysis of
randomized clinical trials. Radiology 212:411-421
4. Imperiale TF and Chalasani N (2001) A meta-analysis of endoscopic variceal ligation for primary prophylaxis of
esophageal variceal bleeding. Hepatology 33:802-807
5. The Veterans Affairs Cooperative Variceal Sclerotherapy Group (1991) Prophylactic sclerotherapy for esophageal
varices in men with alcoholic liver disease. A randomized, single-blind, multicenter clinical trial. N Engl J Med
324:1779-1784
6. Henderson JM et al . (1990) Endoscopic variceal sclerosis compared with distal splenorenal shunt to prevent
recurrent variceal bleeding in cirrhosis. A prospective, randomized trial. Ann Intern Med 112:262-269
7. Rösch J and Keller FS (2001) Transjugular intrahepatic portosystemic shunt: present status, comparison with
endoscopic therapy and shunt surgery, and future prospectives. World J Surg 25:337-346
8. Rosemurgy AS et al . (2000) Transjugular intrahepatic portosystemic shunt vs small-diameter prosthetic H-graft
portacaval shunt: extended follow-up of an expanded randomized prospective trial. J Gastrointest Surg 4:589-597
9. Henderson JM et al . (2004) DSRS vs TIPS for refractory variceal bleeding: a prospective randomized controlled
trial. Hepatology 40:725A [abstract]
10. Freeman RB et al . (2004) Indication for liver transplantation in the MELD Era: Evidence based patient selection.
Liver Transpl 10 (Suppl 2): 51-50
102
Surgery for Bleeding Varices
Dr Prakash Khanduri
The management of bleeding varices is controversial because of the heterogeneous aetiology of
Portal hypertension. Management strategies should take into consideration the aetiology of portal
hypertension, the severity of the liver disease and the expertise available.
The aetiology of portal hypertension in our country differs from that in N. America and Europe where
more than 90% have Cirrhosis, while EHO and NCPF is rarely seen. In contrast 60% of our patients
are non-cirrhotics and among the cirrhotics alcoholic cirrhosis is uncommon. In alcoholic cirrhotics the
risk death following an index bleed may be as high as 30-50%. (1) However in the non cirrhotic and
non-alcoholic cirrhotic who constitute the majority of our patients the risk of death is never more than
10-15% irrespective of the number of bleeding episodes. Therefore Western literature should be
viewed critically and we should plan our own treatment strategies.
There have been major changes in management over the past 60 years. The first Portocaval shunt for
bleeding varices was performed by Whipple and Blakemore in 1945(2,3). During the next 30 years,
surgery was the mainstay of management. In the mid 1970s fibreoptic endoscopy became available
and EST and EVL became the dominant first line therapy.(4) The role of surgery diminished even
though selective shunts and devascularisation procedures were introduced. In the late 1980s because
of the problems associated with sclerotherapy—refractory hemorrhage, evolution of extraoesophageal
varices and complications — shunt surgery was reintroduced. In the late 1980s liver transplant was
introduced which added a new dimension to the management of bleeding varices.(5)
The indication for surgery today are-
 Sclerotherapy failures
 Sclerotherapy complications
 Extra-oesophageal varices
 Portal hypertensive gastropathy
 Extra hepatic obstruction and non cirrhotic portal hypertension.
In the management of variceal bleeding 3 objectives must be met:

1. Bleeding should be effectively controlled
2. Hepatic function preserved.
3. Avoid jeopardizing subsequent liver transplant.
The aim of surgery is to either;

 To decompress the portal system or
 Ablate the variceal bed
The surgical procedures available are:
I. Porto systemic Shunts
These include –Total shunts, Selective shunts, and Partial shunts. Portosystemic shunts are
indicated in
i) Emergency control in sclerotherapy failures in good risk patients.
ii) The elective control of hemorrhage in EHO/ NCPF and
iii) Prophylactic to prevent bleed in EHO.
1. Total Shunts- these shunts divert blood flow away from the liver depriving the hepatocytes of
nutrients and hepatotrophic hormones leading to hepatic encephalopathy, liver atrophy and
failure. Portocaval shunts have a high incidence of encephalopathy and interfere with possible
future transplant. These are generally not performed. Often it is a trade off between
hemorrhage and liver failure. Total shunts include Portocaval (end-to-side / side-to-side),
Mesocaval (end-to-side/ interposition) and the proximal spleno-renal shunt (end-to-side or
side-to-side with preservation of spleen).
103
2. Selective shunts- Because of the high incidence of encephalopathy and deterioration of liver
functions with total shunts, selective shunts were introduced.(6) Warren (1967) introduced the
Distal splenorenal shunt, which selectively decompresses the varices while maintaining
prograde flow to the liver. In this operation the splenic vein is dissected and transected, the
portal end is closed and the splenic end anastomosed to the low pressure left renal vein. The
stomach is devascularised so as to disconnect the oesophago-gastric-splenic segment from
the main portal system.
Although, initially following surgery portal flow to the liver is maintained, but with the passage
of time collaterals develop between the high pressure portal system and the low pressure
oesophago-gastric-splenic segment, reducing the portal flow.(7) Splenopancreatic disconnection,
by dissecting the entire splenic vein off the body and tail of the pancreas prevents the ―pancreatic
siphon‖ which is essential to maintain hepatic portal flow.(8) However the operation is time
consuming with much blood loss. Seven trials compared the distal splenorenal shunt (DSRS) with
various non-selective shunts. There was no survival advantage in either group, but incidence of
hepatic encephalopathy was less after selective shunts.(9) DSRS is contraindicated if ascites is
present or SplenicVein diameter is less than 7 mm as shunt thrombosis occurs. Portal vein
thrombosis develops in 5-10% after DSRS and is fatal in alcoholics.(10) The other selective shunt
is the left gastricocaval shunt which is less commonly employed.
3. Partial Shunts- This is achieved by using small diameter (8-10mm) interposition portocaval or
mesocaval shunts. When shunt diameter is less than 10 mm the hepatic portal flow is
maintained while the varices are decompressed. The incidence of hepatic encephalopathy is
low and shunt thrombosis is <15%.(11) Randomized trial of 8 mm V/s 16 mm portocaval shunts
showed similar survival in both groups but encephalopathy was much less in the 8 mm
growth.(12)
All surgical shunts---Total, Selective and Partial—control bleeding in over 90% of cases.(13) The
incidence of encephalopathy depends on the severity of liver disease and the diversion of portal flow.
Encephalopathy can be reduced by use of selective or partial shunts.
Both EHO and NCPF are common in India and have good liver function.(14) Following shunt surgery
these patients have low mortality rate, and a low incidence of re-bleeding and encephalopathy.(15,16,17)
According to western data EST is superior to shunt surgery.(4,6) However long term results of
sclerotherapy in 2 studies from Chandigarh have shown that re-bleed rates and complications were
much lower following surgery.(18,19) More recently western reports are in agreement with this.(20)
In North America and Europe prophylactic shunts are not performed as it is believed that they do not
improve survival. However many Indian patients living in rural areas have limited medical facilities and
are at risk on dying from a massive bleed. There is also a risk of hepatitis from repeated blood
transfusion.
A study from AIIMS has shown that patients with EHO undergoing proximal; splenorenal shunt have a
95% 15 year survival with no encephalopathy. Prophylactic shunts are therefore offered in patients
with EHO because –
 It provides a one time definitive treatment which is better than EST.
 Avoids the risk associated with multiple transfusions such as hepatitis, HIV.
 Prevents growth retardation in children.
 Helps patients with hypersplenism specially those requiring repeated transfusions.
 Protects against development of portal biliopathy.
However, prophylactic shunts are not recommended in NCPF as a few patients develop nephropathy,
encephalopathy and even myelopathy.
II Non Shunt Operations

The objective is to ablate the variceal bed while maintaining hepatic flow. They include
oesophageal transection alone or in combination with devascularisation of oesophagus and
stomach with or without Splenectomy. Sugiuras procedure includes all of the above. The portal
flow is maintained and the incidence of encephalopathy is low.
104
These are indicated in:
 Emergency control of bleeding in EST failures in poor risk patients
 Electively in failed shunts
 Extensive portal and splenic vein thrombosis, which precludes construction of shunt.
Operations in common use are-

i. Oesophageal Transection
ii. Oesophagogastric devascularization with splenectomy (Hasabs operation for
Schistosomiasis). This is combined with Oesophago-gastric transaction in Tanners
operation.
iii. Sugiuras Procedure (1975); This is a two stage procedure involving transthoracic
oesophageal devascularization and transection in the first stage. In the second stage 3-4
weeks later trans-abdominal devascularization of the abdominal oesophagus and upper
half of stomach combined with splenectomy is performed. In this operation the
oesophagus is meticulously stripped off all vessels from the level of the left inferior
pulmonary vein to upper half of the stomach. Thus all communication between
paraoesophageal veins and veins in the oesophageal wall, the submucosa and the
lamina propria are ligated and transected. The oesophageal veins are then obliterated by
esophageal transection following which the paraoesophageal collaterals drain directly into
the azygos vein. The operation is employed in good risk patients (child A&B) with
excellent results. The operative mortality is 4%, recurrent varices and bleeds 1.5% and no
encephalopathy. The incidence of oesophageal leak is 5.8% and stenosis 2.4%.
III. Orthotopic Liver Transplantation
Bleeding varices do not always indicate advanced liver disease and it is not necessarily an
indication for liver transplantation. A shunt may indefinitely postpone transplant. The United
Network of Organ sharing data has shown there only 35% of listed patient qualified for
transplant. Orloff reported that in 1300 shunts followed for 10 years only 50 qualified for
transplant. Liver transplant is indicated in End-stage liver disease when estimated life
expectancy is less than one year.
Summary
The role of surgery in the management of bleeding varices has diminished Currently the gold standard
for management of bleeding varices is EST/EVL with or without pharmacotherapy. Surgery is
indicated in sclerotherapy failures and in patients with gastric varices or portal gastropathy.
In the Indian context it is to be noted that---
 More than 50% of the portal hypertension in India is related to EHO and NCPF.
 Primarily elective surgery should be offered to all patients with EHO and NCPF in preference
to sclerotherapy. This provides a one time definitive treatment.
 There is a definite place for prophylactic shunting in EHO.
All shunt operations have similar survival figures. The aim of treatment is to stop the initial bleed and
prevent recurrence of hemorrhage by whatever means available. The survival than depends on the
severity of the liver disease. Liver transplantation is an option for End stage liver disease.
Abbreviations
EST-Endoscopic sclerotherapy; EVL-Endoscopic variceal ligation; EHO- Extra hepatic obstruction;
NCPF-Non cirrhotic portal fibrosis;
References
1. Sherlock.S.Portal hypertension. Seminar. Liver Disease.1982.

2. Whipple A.O. The problem of portal hypertension in relation to the hepatosplenopathic Ann. Surg.1945;122—449.
3. Warren W D, Zeppa R, Fomon J J Selective trans-splenic decompression of gastro-oesophageal varices by distal
spleno-renal shunt. Ann. Surg.1967;166: 437—55
4. Westaby D, Williams R. Status of sclerotherapy for variceal bleeding in 1990. Ann. Surg.1990;160: 32-36
5. Starzle T E, Demetris AJ, Van Theil D. Liver Transplantation (1) N. Engl.J. Med 1984; 321: 1014-22.
6. Warren W D, Zeppa R, Fomon J J Selective trans-splenic decompression of gastro-oesophageal varices by distal
spleno-renal shunt. Ann. Surg.1967;166: 437
7. Nouel O et al Long term loss of waner shunt selectivity: Angigraphic demonstration. Arch. Surg. 1981 ; 116: 1121
105
8. HendersonJM, WarrenWD, MillikanWJ et al DSRS with splenopancreatic disconnection: a 4 year assessment.
Ann.Surg.1989: 210: 332
9. Rikkers LF. Is the DSRS better? Hepatology 1988; 8: 1705.
10. Jin G, Rikkers LF . Significant of portal vein thrombosis after distal spleno renal shunt. Arch. Surg. 1991; 126:
1011.
11. Collins JC, Rypins EB, Sarfeh IJ. Narrow diameter portocaval shunts for management of variceal bleeding. World.
J. Surg. 1994; 18:211
12. Sarfeh IJ, Rypins EB. Partial vs Total portocaval shunts in alcoholic cirrhosis. Ann. Surg. 1994; 219: 353
13. Henderson J.M. Surgical management of portal hypertension. Schiffs. Diseases of the liver.pp.443-54 Eighth
Edition. Editors Schiff E R, Sorrell MF, Maddrey W.C. Lippincott-Raven. Publishers, Philadelphia 1999
14. Sarin SK, Tandon BN, Nundy S, Clinical differentiation of the causes of Gastrointestinal bleeding. Ind. J.
Gastroenterol 1986; 5:107-9
15. Mohapatra MK, Mohapatra SK, Sahni P, Nundy S, Encephalopathy in patients with extra hepatic obstruction after
Lieno-Renal shunts. BR.J.Surg. 1992; 79:1103-5
16. Sarin SK, Nundy S, Sub-Clinical encephalopathy in patients with non-cirrhotic portal hypertension. Liver 1985;
5:142-46
17. Prasad AS, ,Gupta S, Kohli V, ,Pande GK, Sahni P, Nundy S. Proximal Leino-renal shunt for extrahepatic portal
venous obstruction in children. Ann. Surg. 1994; 219:193
18. Chawla YK, Dilawari JB, Ramesh GN etal. Sclerotherapy in extrahepatic portal venous obstruction. Gut. 1990; 31:
213-16
19. Bhargava DK, Dwivedi M, Dasrathy S, Arora A. Endoscopic Sclerotherapy for portal hypertension due to
extrahepatic obstruction. Long term followup. Gastrointest. Endosc. 1989; 35: 309-11
20. Iskasson B,, Jeppson B, Bengtssen F, Harrison P, Bengmar S. Mesocaval shunts or repeated sclirotherapy:
effects on rebleeding and encephalopathy: a randomized trial. Surgery 1995; 117: 498-504.
106
Role of Helicobacter Pylori in Acid Peptic Disease
Dr. Manoj Andley
Background: In 1983, Warren (a biologist) and Marshall (a clinician) described Helicobacter pylori
(HP). At first, they named the bacterium Campylobacter pyloridis. Later, it was named Campylobacter
pylori. Since then, a large number of reports have been produced on HP and its pathogenic potential.
In fact, although peptic ulcer disease is the most studied disease related to HP infection, this
bacterium is seemingly involved in the pathogenesis of several extragastric diseases, such as
mucosa-associated lymphoid tissue lymphomas (MALTomas), coronaritis, gastroesophageal reflux
disease, iron deficiency anemia, skin disease, and rheumatological conditions. However, at present,
many of these associations remain largely uncertain, and the debate to confirm or refute causality
related to these associations is still open.
The association of chronic HP infection with alterations in gastric mucosal cell proliferation is
recognized worldwide. In addition, HP can produce and release several bioactive factors that may
directly affect the stomach's parietal cells, which produce hydrochloric acid, and enterochromaffin like
(ECL) cells (ie, G cells and D cells), which produce gastrin and somatostatin, respectively. Evidence
suggests that HP inhibits D cells and stimulates G cells. HP has some control mechanisms able to
switch the transcription of different genes on or off when needed.
A strong association has been reported between HP infection and gastric lymphoma and
adenocarcinoma of the body and antrum of the stomach. Some cofactors may play a key role in
determining such diseases. Currently, whether HP eradication can decrease the risk of cancer
remains unknown.
HP infection occurs more frequently in developing countries than in industrialized countries. HP

strains differ in their potential to cause diseases. Although anyone can develop a microscopic
gastritis, only a minority of infected persons develop ulcers or other diseases.
In the last 12 years, some Helicobacter-like organisms (HLOs) have been detected by specific
polymerase chain reaction tests. The first of these HLOs was described in ferrets and is called
Helicobacter mustelae. More recently, Helicobacter hepaticus has been described in Syrian hamsters.
These HLOs are useful for researching HP infection modalities.
Pathophysiology: The most common route of HP infection is either oral-to-oral (stomach contents
are transmitted from mouth to mouth) or fecal-to-oral (from stool to mouth) contact. Parents and
siblings seem to play a primary role in transmission.
In a susceptible host, HP determines chronic active gastritis that may lead, in turn, to duodenal and
gastric ulcer disease, gastric cancer, and MALTomas. HP infection causes chronic active gastritis,
which is characterized by a striking infiltrate of the gastric epithelium and the underlying lamina
propria by neutrophils, T and B lymphocytes, macrophages, and mast cells. Mast cells, usually
responsible for the immune response balance, may be important effector cells in the pathogenesis of
gastritis. However, HP does not seem to invade the gastric mucosa, although evidence suggests that
the mucus creates a niche wherein the germ is protected from gastric secretions.
The release of host cytokines after direct contact of HP with epithelial cells of the gastric lining could
recall the inflammatory cells in the infected area. A recent study has demonstrated that gastric
epithelium, when infiltrated by neutrophils and macrophages in the lamina propria, highly express 2
neutrophil chemotactic factors: gro-alpha, and interleukin-8. In addition, the interferon-gamma
inducible protein–10 (IP-10) and the monokine induced by interferon-gamma (MIG), 2 selective
chemotactic factors for T lymphocytes, are expressed by the endothelium and mononuclear cells of
gastric mucosa in patients with HP-related gastritis. According to the same study, gro-alpha and
interleukin-8 may have a central role in neutrophils trafficking from the vessels to the mucosal
epithelium, while IP-10 and MIG determine T lymphocyte recruitment into the mucosa.
Another hypothesis states that HP may recall immune cells from afar because of its own molecules,
such as urea or lipopolysaccharide (LPS). Outer-membrane permeability is a function mediated by
107
LPS. Despite the presence of bacterial LPS in biologically active quantities in the gastric mucosa, the
mechanisms by which it may recall the immune cells are still unknown. According to one hypothesis,
HP may induce the production of autoantibodies against the host's gastric lining.
The LPS of HP shows certain blood group antigens such as Leb, Lex, Ley, and H-type I. Such antigens
are thought to represent important virulence factors involved in the adhesive process of the germ. Leb
constitutes an adhesin, and differences exist in the Le compositions of adherent and nonadherent
bacteria. This, perhaps, accounts for a relationship between adhesion and Le expression. In addition,
any Le antigen shows phase variation leading to the spontaneous and random switching on and off of
the expression of these antigens. For example, the H-type I antigen seems to be the result of a
reversible singular nucleotidic deletion/insertion in a tract of a glycosyl transferase gene. The LPS of
the HP also seems to influence tumoral proliferation of ECL cells, stimulating the intracellular
polyamine biosynthesis pathway and ornithine decarboxylase activity by the activation of a CD14
receptor on the ECL cell.
In 1997, Tomb and coworkers completely sequenced the HP genome, and some differences were
found in gene encoding factors that are likely to interact with the host, such as surface proteins. Two
of the most important genes of HP are VACA and CAGA. The VACA gene codes for the Vac-A
cytotoxin, a vacuolizating toxin. Most HP strains (60%), by unexplained causes, do not produce this
protein. The CAGA gene codes for the Cag-A protein, which seems to stimulate the production of
chemotactic factors for the neutrophils by the gastric epithelium of the host. A certain portion of HP
strains (40%), by unexplained causes, does not produce this protein.
After the exposure to CAGA-positive HP strains, an increase has been reported in catalase,
glutathione peroxidase, and superoxide dismutase activity. This increase is associated with fewer
DNA adducts and reduced susceptibility of the gastric cells to the irreversible injuries from reactive
oxygen species (ROS) compared with exposure to CAGA-negative HP strains. Such alterations of the
ROS scavenging enzymes may partly account for the increased risk of gastric cancer in individuals
with HP infection.
A relationship among CAGA/Cag-A, VACA alleles, and the Le subtype of HP strains has been
reported, as has a link between these and the redox status of the gastric mucosa. For example, HP is
able to induce apoptosis in epithelial cells and T lymphocytes. The CAGA-positive strains of HP seem
to be able to increase FASL expression in T lymphocytes (up-regulation of FASL on such cells is
redox-sensitive), which facilitates a selective killing of the T lymphocytes. This molecular mechanism
may have a key role in the persistence of CAGA-positive strains.
In addition, HP up-regulates caspases 3, 6, 8, and 9. Caspases 3 and 9 in epithelial cells are

fundamental in inducing apoptosis. The expression of some bacterial genes is acid-regulated, as
reported for the FILA gene (responsible for the HP motility) that codes for a sigma factor required for
transcription of the flagellin gene FLAA. Flagella and urease are very important for the colonization of
the gastric mucosa by the bacterium.
Frequency:
 In the US: The frequency of HP infection may be linked to race. White persons account for
29% of cases, and Hispanic persons account for 60% of cases.
 Internationally: HP is a ubiquitous organism. At least half of all people are infected, but an
exact determination is not available, mostly because exact data are not available from
developing countries. HP may be detected in approximately 90% of individuals with peptic
ulcer disease; however, less than 15% of infected persons may have this disease.
Mortality/Morbidity: The mortality rate related to HP infection is not precisely known, but it seems to
be minimal (ie, approximately 2-4% of all infected people). Mortality is due to the complications of the
infection, such as gastric ulcer perforation or MALTomas of the GI tract. Otherwise, the morbidity of
HP infection can be very high.
Race: The pathogenetic role of HP may differ depending on geography and race. White persons are
infected with HP less frequently than persons of other racial groups. The prevalence rate is
approximately 20% in white persons, 54% in African American persons, and 60% in Hispanic persons.
108
Sex: No sex predilection is known; however, females have a higher incidence of reinfection (5-8%)
than males.
Age: HP infection may be acquired at any age. According to some epidemiologic studies, this
infection is acquired most frequently during childhood. Children and females have a higher incidence
of reinfection (5-8%) than adult males.
Clinical Diagnosis
History: No significant differences in the presence and frequency of symptoms, such as nausea,
vomiting, pain, heartburn, or diarrhea, occur in patients who are infected with HP and patients who are
not. No definite evidence demonstrates a clear relationship between the symptoms of the HP-
associated gastritis and abdominal pain or dyspeptic symptoms from other conditions. Of patients, 30-
35% have no symptoms.
 Adults and children differ in immune response to HP infection. This is probably due to a
physiologic lower density of neutrophils and T lymphocytes during childhood, especially in
children younger than 8 years.
 Although HP infection is not significantly related to recurrent abdominal pain, weekly pain is
reported more often in children who are infected with HP compared with children who are not
infected.
Physical: No specific clinical signs have been described in patients with HP infection.
 Patients may feel dyspepsia or abdominal discomfort, such as during gastritis or with
epigastric pain (eg, duodenal ulcers).
 In some cases, patients may feel hungry in the morning and may have halitosis.
Causes:
 HP infection causes atrophic and even metaplastic changes in the stomach.
 The bacterial adhesion appears to result in tyrosin phosphorylation and is specific for gastric
cells.
 The adhesion of HP to the gastric cells causes a direct decrease in mucosal levels of
glutathione, a fundamental molecule in the maintenance of the cellular redox status and in the
molecular regulation of host immune responses. However, the LPS of HP may induce the
production of autoantibodies that are able to worsen atrophy in the corpus mucosa and cause
a concomitant increase in parietal cell antibodies. Such events are accompanied by a
decrease in anti-HP immunoglobulin titers. This process leads to a scenario of severe atrophy
without bacterial colonization combined with high levels of autoantibodies against gastric
parietal cells.
 A number of reports show the close association between HP infection and low-grade gastric
MALToms
Histologic Findings: HP is a gram-negative bacterium. It produces urease, has a spirallike

conformation, and is microaerophilic and motile because of the flagella. Flagella and urease are very
important for its colonization of the gastric mucosa. Urease neutralizes gastric acidity, converting the
gastric urea to ammonium ions, and flagella help the bacterium pass from the acidic gastric lumen into
the mucus of the stomach. Two of the most important genes of HP are VACA and CAGA. The VACA
gene codes the Vac-A cytotoxin, a vacuolizating toxin, and the CAGA gene codes for Cag-A protein,
which seems to stimulate the production of chemotactic factors for the neutrophils by the gastric
epithelium of the host.
Biopsy specimens from EGD, stained with Giemsa stain, usually demonstrate a variable number of
HP organisms adhering to the gastric epithelium, both coating the gastric wall and lining the gastric
glands. The mucous film appears decreased. A large inflammatory infiltrate is present, with
lymphocytes, neutrophils, and a variable number of mast cells that seem to play an important role in
the pathogenesis of the gastric injury of persons infected with HP. Other stains are Genta, Warthin-
Starry silver, and the classic hematoxylin and eosin. A rapid urease test may demonstrate the
109
presence of the HP in the gastric mucosa via histochemistry results. Bacterial culture is very difficult. It
is not used for diagnosis; it is used for experimental purposes only.
Staging: Although a staging system for the HP infection does not exist, some steps of the disease are
well described. The first step is chronic gastritis, followed after a time by the second step, atrophic
gastritis. The third step is intestinal metaplasia, which may evolve into dysplasia. The last step in this
process is gastric adenocarcinoma. This process is very slow and may stop at any step because
gastric cancers undoubtedly require several other factors to develop, not only an HP infection. As
reported above, ultrasound and EGD should be considered in patients with gastric MALTomas in
order to allow a more precise staging of the disease.
Medical Care: Only treat patients who have a test result positive for HP infection. Carefully educate
patients regarding the importance of completing the prescription and about the potential adverse
effects of the medication. Importantly, consider possible antibiotic resistance when selecting the
treatment regimen.
 The US Food and Drug Administration has approved some regimens, which are now
accepted internationally, for the treatment of HP infection in patients with peptic ulcer disease,
both gastric and duodenal.
These regimens are also known as triple therapies and have reported cure rates from 85-90
110
Update on GERD diagnosis and management
Dr. A.S.Puri
Definition
The ACG guidelines define GERD as "symptoms or mucosal damage produced by the abnormal
reflux of gastric contents into the esophagus." Reflux esophagitis is a condition experienced by a
subset of GERD patients with endoscopically evident lesions in the esophageal mucosa. Patients with
Nonerosive reflux disease often have symptoms of gastroesophageal reflux often in the absence of
esophagitis, and 24-hour esophageal pH monitoring can be helpful in identifying this subset of
patients.
Epidemiology
There is substantial geographic variation in prevalence with very low rates in Africa and Asia and high
rates in North America and Europe. The incidence and prevalence figures are based more on
estimates than on actual data. This difficulty occurs partly because GERD and esophagitis cannot be
differentiated by a clinical history and partly because there is no gold standard for the recognition or
exclusion of GERD. A cross-sectional hospital based study found that 7% of individuals experienced
heartburn daily, 14% weekly, and 15% monthly. Ambulatory esophageal pH monitoring to define
GERD found that 48% to 79% of patients with pathologic acid exposure had esophagitis.
GERD is equally prevalent among men and women, but there is a male preponderance of esophagitis
(2 :1 to 3 :1) and of Barrett's metaplasia (10 :1).Pregnancy is associated with the highest incidence of
GERD: 48% to 79% of pregnant women complain of heartburn.
GERD can cause histopathologic changes to the esophageal epithelium even without endoscopically
evident esophagitis. When mucosal erosions are evident endoscopically, histopathologic findings
include severe epithelial injury usually accompanied by neutrophilic or eosinophilic infiltration.
PATHOGENESIS
The fundamental abnormality in GERD is exposure of esophageal or supra-esophageal epithelium to

gastric secretions that results in either histopathologic injury or elicitation of symptoms.
A prerequisite for GERD is gastroesophageal reflux, an event normally prevented by a competent

esophagogastric junction. The functional integrity of the esophagogastric junction has been attributed
to numerous anatomic and physiologic mechanisms including intrinsic LES pressure, extrinsic
compression of the LES by the crural diaphragm, the intra-abdominal location of the LES, integrity of
the phrenoesophageal ligament, and maintenance of the acute angle of His between the distal
esophagus and proximal stomach with its flap valve function.
Investigations have focused on three dominant mechanisms of esophagogastric junction

incompetence: (1) transient LES relaxations without anatomic abnormality, (2) LES hypotension
without anatomic abnormality, and (3) anatomic distortion of the esophagogastric junction inclusive of,
but not limited to, hiatal hernia. The dominant mechanism may vary with disease severity with
transient LES relaxations dominant in mild disease and mechanisms associated with hiatal hernia
and/or a weak sphincter dominant in more severe disease.
The role of Helicobacter pylori in GERD deserves special attention as GERD patients with esophagitis
are less likely to have H. pylori infection. H. pylori infection is also associated with a decreased
prevalence of Barrett's metaplasia. This epidemiologic data have led some to believe thatH. pylori
should not be eradicated in patients with GERD. Since H. pylori is a risk factor for the development of
peptic ulcer and gastric cancer, Currently, this issue is not resolved.
111
CLINICAL PRESENTATION AND NATURAL HISTORY
The most common symptoms of GERD are heartburn, acid regurgitation, and dysphagia. Although
there is some correlation between frequency of heartburn, degree of esophageal acid exposure, and
presence or extent of mucosal injury, this correlation is far from perfect. Some patients with severe
esophagitis or Barrett's metaplasia do not report having any heartburn.
Typical Symptoms
Some degree of dysphagia is reported by more than 30% of individuals with GERD. It can be caused
by peptic stricture, a Schatzki ring (B ring), peristaltic dysfunction, or simple mucosal inflammation.
Dysphagia also occurs in the absence of any identifiable abnormality, in which case it is likely the
result of abnormal sensitivity to bolus movement during peristalsis. Other, less common symptoms of
reflux disease include water brash, globus sensation, and odynophagia.
Atypical Symptoms:
Patients with GERD may present with atypical symptoms like posterior laryngitis, asthma, dry cough
and non cardiac chest pain.
Posterior Laryngitis: 4% to 10% of patients of posterior laryngitis have reflux-related disease and that
patients who have esophagitis are twice as likely to have laryngitis as those who do not.
Asthma: Epidemiologic studies subsequently confirmed this association. A case control

questionnaire based survey of a large group of asthmatic and control subjects found that 77% of
asthmatic subjects reported heartburn and 55% reported regurgitation, significantly more than the
controls.
Noncardiac Chest Pain: Esophageal pH monitoring studies reported that abnormal acid exposure
was often present in patients who had noncardiac chest pain and, more importantly, that episodes of
chest pain were often associated with reflux.
Natural History
Patients seeking medical attention for GERD typically report having had symptoms for 1 to 3 years
prior to seeking medical attention.Beyond that, little information exists on the natural history of GERD.
The prevalence of peptic stricture in patients with esophagitis ranges from 8% to 20% and that of
ulceration is 5%. Recently these complication rates are decreasing, most likely because of
widespread use of proton pump inhibitors.
Differential Diagnosis
Although generally quite characteristic, symptoms of GERD must be distinguished from symptoms
related to infectious esophagitis, pill esophagitis, peptic ulcer disease, dyspepsia, biliary colic,
coronary artery disease, and esophageal motor disorders.
MANAGEMENT
It is neither practical nor necessary to embark on a diagnostic evaluation of every patient who
experiences only heartburn. The primary goal of therapy in these patients is symptom relief.
Diagnostic evaluation can, however, be useful in selected GERD patients to confirm the diagnosis,
direct therapy, or identify complications.
Diagnostic Evaluation
The history is usually sufficient to confirm the diagnosis of GERD and to warrant appropriate
treatment. However, GERD patients can also have atypical symptoms, leaving one to rely on
diagnostic studies to confirm that abnormal acid reflux is occurring and potentially responsible for the
syndrome in question. Diagnostic studies are also indicated for a GERD patient when heartburn is
extremely chronic (raising the possibility of Barrett's metaplasia), refractory to treatment, or
accompanied by the so-called warning signs of dysphagia, odynophagia, gastrointestinal bleeding, or
weight loss.
ENDOSCOPY
Endoscopy should be used as the first diagnostic test of suspected GERD because it provides a
means for both detecting and managing complications of GERD as well as excluding other diseases.
112
Endoscopy is diagnostic of GERD if erosive esophagitis is present, with a specificity of 90% to 95%.
However, because only 30% to 40% of patients with GERD have esophagitis indicated by endoscopy.
AMBULATORY REFLUX MONITORING

Evidence Level III: Best tool for studying actual amounts of reflux in a given patient with high
sensitivity and specificity (96 %). It can help confirm reflux in patients with normal endoscopic
findings, and in those whose symptoms continue despite an acid-suppression trial or therapy.
In the future, ambulatory testing may be achieved by radiotelemetry capsule monitoring (BRAVO), in
which a capsule is attached to the esophageal mucosa, or combined impedance and acid testing to
measure acid and nonacid reflux.
Esophageal manometry (Evidence Level III)
Useful for excluding rare motility disorders such as achalasia and scleroderma in patients being
considered for antireflux surgery, and also has been used preoperatively to measure peristalsis.
Table 1.
Diagnostic Tools for Gastroesophageal Reflux Disease
Methods Comments
Endoscopy Typical symptoms with endoscopic changes 97
percent specific for GERD; preferred technique
for diagnosing complications of GERD.
Ambulatory pH Best tool for studying actual reflux amounts; can

reflux monitoring confirm diagnosis in patients with normal
endoscopy results or unresponsive symptoms;
highly sensitive and specific for erosive
esophagitis
Esophageal Useful preoperatively for excluding rare motility

manometry disorders.
LIFESTYLE MODIFICATION (Evidence Level IV)
The results of most randomized trials show a 20 to 30 percent response to symptoms of GERD with
placebo therapy, and this often is attributed to lifestyle modifications. Life-style modifications include
head of the bed elevation, avoidance of tight fitting garments, weight loss, dietary modification,
restriction of alcohol use and elimination of smoking are often useful. These interventions are aimed
at enhancing esophageal acid clearance, minimizing the occurrence of acid reflux, or doing both..
Acid Suppressive Medications (Evidence Level I).

The object of these therapies is to raise the intragastric pH above 4 during the periods of the day that
reflux is likely to occur. There are four H2 receptor antagonists (cimetidine, ranitidine, famotidine, and
nizatidine) and five proton pump inhibitors (omeprazole, lansoprazole, rabeprazole, pantoprazole, and
esomeprazole magnesium) currently in clinical use. Proton pump inhibitors suppress acid much more
effectively than any H2 receptor antagonist dosage because they act on the final common pathway of
acid secretion.
All of the H2 receptor antagonists demonstrate a therapeutic gain of only 10% to 24% relative to
placebo for healing esophagitis regardless of esophagitis severity or the dose of H2 receptor
antagonist used. The proton pump inhibitors, on the other hand, demonstrate increasing therapeutic
gain with increasing esophagitis severity and the efficacy of the proton pump inhibitors increases with
increasing dosage and/or potency.
Prokinetic Drugs (Evidence Level II)

An ideal therapy would be to target the pathophysiologic abnormalities of GERD, thereby obviating
the need for acid suppression. Most recently, metoclopramide and cisapride have been used, but
113
unfortunately these agents have minimal effect on relevant motor function and are associated with
significant side effects. The cholecystokinin A (CCKA) antagonist loxiglumide decreases transient LES
relaxations stimulated by gastric distension. l-Baclofen, a γ -aminobutyric acid B (GABAB) receptor
agonist, is yet another agent reported to decrease transient LES relaxations in humans.
Maintenance Therapy (Evidence Level I.)

Although almost all severe esophagitis could be healed with proton pump inhibitor therapy, recurrence
occurred in approximately 80% of patients within 6 months of discontinuation of therapy, and the
likelihood of recurrence was related to the initial severity of esophagitis. Current evidence suggests
that maintenance therapy with either H2 receptor antagonists or cisapride is significantly less effective
than therapy with proton pump inhibitors.
Antireflux Surgery (Evidence Level II)
Whether antireflux surgery is as good as or superior to modern medical therapy is difficult to

ascertain. Currently there are no valid data comparing laparoscopic antireflux therapy to long-term
proton pump inhibitor therapy. Thus, the decision to pursue medical or surgical therapy ultimately
depends on a risk-to-benefit analysis.
Indications of antireflux surgery

1. Failed medical therapy, with persistent symptomatic esophagitis.
2. Young healthy patient unwilling to take, or intolerant of, long-term PPI therapy.
3. Persistent symptoms due to regurgitation (laryngitis, asthma, bronchiectasis).
A strong argument against antireflux surgery can be made for the following individuals:
(1) elderly patients with concomitant disease and high surgical risk,
(2) patients with continued symptoms but without quantifiable abnormal reflux,
(3) patients with concomitant bloating or functional symptoms likely to be made worse by
fundoplication, and
(4) patients with poor or absent peristaltic function who are at risk of development of severe
dysphagia after fundoplication.
Type of surgery:
Although many operations have been devised to control reflux disease, currently, the two most
popular procedures are the laparoscopic Nissen (360-degree) fundoplication and the Toupet (270-
degree) fundoplication. Regardless of whether the procedures are done in an open or laparoscopic
fashion they likely work similarly. Unlike medical therapy, fundoplication, via both mechanical and
physiologic modifications, attempts to correct the underlying abnormalities associated with GERD.
The essential procedure of fundoplication is to mobilize the lower esophagus, reduce the associated
hiatal hernia, and wrap the gastric fundus either partially or totally around the esophagus. The
operation reestablishes competence of the antireflux barrier by repairing the hiatal hernia and
increasing resting LES pressure.
Endoscopic therapy (Evidence Level III)

Endoscopic therapy is relatively new, and systematic reviews have found no definite indications for its
use. However, select well-informed patients with well-documented GERD that is responsive to therapy
with PPIs may benefit from the procedure.
Three categories of endoscopic technique have been studied: (1) radiofrequency application to
increase the lower esophageal sphincter reflux barrier; (2) endoscopic sewing devices; and (3)
injection of a nonresorbable polymer into the lower esophageal sphincter area. All techniques seemed
to improve reflux symptoms, but normalization of intraesophageal acid exposure was limited and there
were no significant changes in lower esophageal sphincter pressure. Possible complications of
radiofrequency application include perforation, hemorrhage, and death. Data are needed on the long-
term durability and safety of endoscopic techniques, their usefulness in patients with atypical GERD,
and their efficacy outside the study setting.
114
Peptic Ulcer Disease Today
Yuhong Yuan; Ireneusz T Padol; Richard H Hunt
Nat Clin Pract Gastroenterol Hepatol. 2006;3(2):80-89.
Summary
Over the past few decades, since the introduction of histamine H2-receptor antagonists, proton-pump
inhibitors, cyclo-oxygenase-2-selective anti-inflammatory drugs (coxibs), and eradication of
Helicobacter pylori infection, the incidence of peptic ulcer disease and ulcer complications has
decreased. There has, however, been an increase in ulcer bleeding, especially in elderly patients. At
present, there are several management issues that need to be solved: how to manage H. pylori
infection when eradication failure rates are high; how best to prevent ulcers developing and recurring
in nonsteroidal anti-inflammatory drug (NSAID) and aspirin users; and how to treat non-NSAID, non-
H. pylori-associated peptic ulcers. Looking for H. pylori infection, the overt or surreptitious use of
NSAIDs and/or aspirin, and the possibility of an acid hypersecretory state are important diagnostic
considerations that determine the therapeutic approach. Combined treatment with antisecretory
therapy and antibiotics for 1-2 weeks is the first-line choice for H. pylori eradication therapy. For
patients at risk of developing an ulcer or ulcer complications, it is important to choose carefully which
anti-inflammatory drugs, nonselective NSAIDs or coxibs to use, based on a risk assessment of the
patient, especially if the high-risk patient also requires aspirin. Testing for and eradicating H. pylori
infection in patients is recommended before starting NSAID therapy, and for those currently taking
NSAIDs, when there is a history of ulcers or ulcer complications. Understanding the pathophysiology
and best treatment strategies for non-NSAID, non-H. pylori-associated peptic ulcers presents a
challenge.
Introduction
For more than a century, peptic ulcer disease was most often managed surgically, with resulting high
morbidity and mortality rates. Effective pharmacologic suppression of gastric acid secretion began
with the introduction of histamine H2-receptor antagonists (H2RAs) in the 1970s, which greatly
improved clinical outcomes. During the 1980s elective peptic ulcer surgery declined by 85%, which
can be mainly attributed to the use of the H2RAs cimetidine and ranitidine.[1] The development of
proton-pump inhibitors (PPIs) further improved inhibition of gastric acid secretion, and the lack of
tachyphylaxis to PPI therapy ensures very high healing rates for duodenal and gastric ulcers.[2]
It is now over 20 years since the advent of the 'H. pylori era' and we are now at something of a
plateau in our understanding, diagnosis and treatment of peptic ulcer disease. Three main issues
remain to be resolved. We must find the optimal way to eradicate H. pylori in a time of increasing
eradication failure rates, we need to find the best method to prevent ulcer development and ulcer
recurrence in NSAID users, and we must discover how best to treat non-NSAID, non-H. pylori-
associated peptic ulcers. The worldwide ulcer prevalence differs, with duodenal ulcers dominating in
Western populations and gastric ulcers being more frequent in Asia, especially in Japan.[3] Although
the incidence of peptic ulcer disease in Western countries has declined over the past 100 years,
around 1 in 10 Americans are still affected.[4] The annual financial burden of peptic ulcer disease in
the US, including direct and indirect costs, is estimated as US$3.4 billion.[5] Since peptic ulcer disease
is still common, and peaks in the elderly, it is expected that its impact on human health and health
economics will remain an important issue in the future.
Pathophysiology of Peptic Ulcer Disease

Historically, our understanding of the pathophysiology of peptic ulcer disease focused on
abnormalities in the secretion of gastric acid and pepsin, and on the suppression of acid as a
treatment strategy. Today, gastric hypersecretion—associated with gastrinoma in Zollinger-Ellison
syndrome, antral G-cell hyperplasia, an increase in parietal-cell mass, and a physiological imbalance
between the antagonistic gastric hormones gastrin and somatostatin—is still an important issue in
peptic ulcer disease. Moreover, it is known that cholinergic hypersensitivity and parasympathetic
dominance are related to the stimulation not only of hydrochloric acid but also pepsin, which is often
neglected as a cofactor in the development of erosive injury to the gastric mucosa. Psychologic
stress, cigarette smoking, alcohol consumption, use of nonsteroidal anti-inflammatory drugs (NSAIDs)
including aspirin, oral bisphosphonates, potassium chloride, immunosuppressive medications, and an
age-related decline in prostaglandin levels have all been shown to contribute to peptic ulcer disease.[6]
It was, however, the isolation of H. pylori and its identification as the most important cause of peptic
115
ulcer disease that led to exploration of the role of inflammation and its associated cytokine cascade in
gastric acid secretion.
H. pylori evades attack by the host immune system and causes chronic, indolent inflammation by
several mechanisms. H. pylori can damage the mucosal defense system by reducing the thickness of
the mucus gel layer, diminishing mucosal blood flow, and interacting with the gastric epithelium
throughout all stages of the infection. H. pylori infection can also increase gastric acid secretion; by
producing various antigens, virulence factors, and soluble mediators, H. pylori induces inflammation,
which increases parietal-cell mass and, therefore, the capacity to secrete acid. The H. pylori cytotoxin-
associated gene CagA also has an important role: it interferes with gastric epithelial cell-signaling
pathways, thereby regulating cellular responses and possibly contributing to apical junction barrier
disruption, interleukin-8 secretion and phenotypic changes to gastric epithelial cells.[7]
Understanding the pathophysiology of peptic ulcer disease is at something of a crossroads:

mechanisms of injury differ distinctly between duodenal and gastric ulcers. Duodenal ulcer is
essentially an H. pylori-related disease and is caused mainly by an increase in acid and pepsin load,
and gastric metaplasia in the duodenal cap.[8] Gastric ulcer, at least in Western countries, is most
commonly associated with NSAID ingestion, although H. pylori infection might also be present.[9]
Chronic, superficial and atrophic gastritis predominate in patients with gastric ulcers, when even
normal acid levels can be associated with mucosal ulceration.[10] In both conditions, ulcer is
associated with an imbalance between protective and aggressive factors, with inflammation being a
leading cause of this imbalance.
The isolation of H. pylori in the early 1980s was one of the most exciting advances in the history of
peptic ulcer disease,[11] and it has dramatically changed the management of peptic ulcer. Eradication
of H. pylori infection is now the mainstay of treatment for peptic ulcer disease, and has resulted in
very high ulcer healing rates and recurrence rates that have dropped dramatically, especially for
individuals with a duodenal ulcer. The greater recognition of the role of NSAIDs and aspirin in
gastrointestinal-tract injury has led to the development of therapeutic and preventive strategies that
rely on the use of antisecretory drugs, the prostaglandin analogue misoprostol, or selective cyclo-
oxygenase (COX)-2 inhibitors (coxibs).
H. pylori-associated Ulcer
During the 1980s, H. pylori infection was found in more than 90% of patients with duodenal ulcers,
and some 70% of patients with gastric ulcers.[12, 13] The declining incidence and prevalence of peptic
ulcer in developed countries has paralleled the falling prevalence of H. pylori infection,[14] especially in
populations with high infection rates.[15] Only H. pylori eradication is an effective treatment for both
duodenal and gastric ulcers. Antisecretory drugs work well for controlling symptoms and allowing
ulcers to heal, and the absolute benefit of eradicating H. pylori infection is small with respect to
healing alone. In a Cochrane meta-analysis the eradication of H. pylori infection combined with the
use of an ulcer-healing drug significantly increased duodenal healing to 83% (intent-to-treat analysis),
with the relative risk of the ulcer persisting being 0.66 (95% CI 0.58-0.76) compared with the ulcer-
healing drugs alone; but eradication was not significantly superior to ulcer-healing drugs for gastric-
ulcer healing (relative risk 1.32; 95% CI 0.92-1.90).[16]
NSAID-induced Injury
Despite their well-accepted anti-inflammatory and analgesic benefits, NSAID use is probably the most
common cause of gastrointestinal mucosal injury in Western countries. NSAIDs, including aspirin,
significantly increase the risk of adverse gastrointestinal events, particularly those related to gastric
and/or duodenal mucosal injury: erosions, ulcers and ulcer complications, especially bleeding.[17]
About 15-30% of regular NSAID users have one or more ulcers when examined endoscopically, and
3-4.5% of NSAID users have clinically significant upper gastrointestinal events, including ulcers and
ulcer complications.
Patients taking low-dose aspirin for the prevention of a cardiovascular event, such as myocardial
infarction or thrombotic stroke, are also at increased risk of gastrointestinal injury and
complications.[18] In asymptomatic patients taking low-dose aspirin (75-325 mg/day) for ≥3 months,
endoscopically observed ulcers or erosions are reported in 47.83% of cases.[19] The risk of upper
gastrointestinal bleeding events is dose-dependent, with an odds ratio (OR) of 3.3 for 300 mg of
aspirin (95% CI 1.2-9.0) and an OR of 6.4 for 1.2 g of aspirin (95% CI 2.5-16.5).[20] In multivariate
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models adjusted for age, sex, and clinical risk, low-dose aspirin alone was independently associated
with an increased risk of ulcer bleeding, with an OR of 2.4 (95% CI 1.8-3.3).[21]
The injurious gastrointestinal effects of NSAIDs are largely caused by the inhibition of COX1 and its
role in normal mucosal defense mechanisms (discussed above), and also through the inhibition of
thromboxane A2, which compromises platelet function and results in gastrointestinal bleeding. Clinical
trials have repeatedly demonstrated that coxibs are associated with fewer ulcers, less gastrointestinal
bleeding and fewer ulcer complications than nonselective NSAIDs,[22, 23, 24, 25] but concurrent use of
low-dose aspirin blunts this benefit.[22] It is expected that the withdrawal of several coxibs will lead to
many patients switching back to nonselective NSAIDs, with an anticipated increase in cases of
gastrointestinal bleeding, especially in elderly patients.
Impact of H. pylori Infection on NSAID-induced Injury

H. pylori infection and NSAIDs are independent risk factors for peptic ulcer disease that have additive
or synergistic effects on adverse gastrointestinal outcomes (Figure 1). In a meta-analysis, the OR for
the incidence of peptic ulcer was 61.1 in patients infected with H. pylori and also taking NSAIDs,
compared with uninfected controls not taking NSAIDs.[26] The OR narrowed to 18.1 when comparing
H. pylori-infected patients with H. pylori-uninfected patients who were not taking NSAIDs.[26]H. pylori
infection also potentiates the ulcer bleeding induced by low-dose aspirin.[27] Together, H. pylori
infection and NSAID use account for approximately 90% of peptic ulcer disease.
Figure 1.
Helicobacter pylori and nonsteroidal anti-inflammatory drugs have synergistic effects on gastric
mucosal damage. Both H. plyori infection and NSAID use have been found to independently and
significantly increase the risk of gastric and duodenal mucosal damage and ulceration. H. pylori and
NSAIDs act synergistically through pathways of inflammation in the development of ulcers and in ulcer
bleeding.
Both H. pylori infection and NSAID use have been found to independently and significantly increase
the risk of gastric and duodenal mucosal damage and ulceration. H. pylori and NSAIDs act
synergistically through pathways of inflammation in the development of ulcers and in ulcer bleeding.
Diagnosis of Peptic Ulcer Disease

Symptoms of peptic ulcer disease commonly include epigastric pain, postprandial pain and nocturnal
pain, pain that can wake the patient from sleep, and pain relieved by food or antacids. Less-common
features include anemia caused by gastrointestinal blood loss, weight loss attributed to a reduced
appetite caused by fear of pain, and vomiting associated with a gastric ulcer or pyloric stenosis. Pain
does not define an ulcer, however, and the absence of pain does not preclude the diagnosis,
especially in the elderly, who can present with 'silent' ulcer complications. No specific symptom helps
differentiate between H. pylori-associated or NSAID-associated ulcers, but a careful history can
identify surreptitious NSAID users and an appropriate H. pylori test can detect infected individuals.
Endoscopy is essential for an accurate diagnosis and differential diagnosis of peptic ulcer disease and
ulcer complications (e.g. a gastric ulcer can be biopsied to exclude malignancy or to obtain tissue for
117
an H. pylori diagnostic test). Endoscopic healing is the gold standard used to evaluate ulcer healing in
clinical trials. In clinical practice, many patients with dyspepsia symptoms might be tested and treated
for H. pylori infection in primary practice without endoscopic evaluation. Guidelines have
recommended this approach in young dyspepsia patients without alarm symptoms[28] as H. pylori 'test
and treat' is more cost-effective than endoscopy in this group of patients.[29] A small proportion of
dyspepsia patients will, therefore, have their ulcer cured without a formal diagnosis being made.
Testing for H. Pylori Infection

There are currently several methods to test for H. pylori infection. Methods that require endoscopy
include culture and histologic examination, the rapid urease test (RUT), and polymerase chain
reaction (PCR) of gastric biopsy specimens. PCR is very sensitive but prone to producing false-
positive results. Non-endoscopic tests include the 13C-urea or 14C-urea breath test (UBT), serology or
an H. pylori stool antigen test. The choice of initial test for H. pylori detection is also dependent on the
prevalence of H. pylori infection in the population, because the positive and negative predictive values
of a single test change according to the prevalence of the infection.[30]
Tests can reveal active or past infection. The best test for the detection of an active infection is the
UBT.[30] In practice, however, when a patient with peptic ulcer disease undergoes endoscopy, a RUT
can be used initially and a second test performed if there is a negative result. For each test there are
several considerations (e.g. methodologic, technical and the impact of treatment) that must be taken
into account to make the best choice for H. pylori testing in a particular clinical setting. For example,
serology tests, which rely on the presence of anti-H. pylori antibody, do not identify active infection.[30]
Both the RUT and the UBT, however, are influenced by PPI or antibiotic treatment, which inhibit
urease activity and directly affect test sensitivity and specificity.[31, 32]
Eradication of infection should be confirmed after the end of therapy; noninvasive testing with the UBT
is the preferred choice, 4-8 weeks after the completion of therapy.[33] If the ulcer recurs after
eradication therapy, a more careful search for reinfection or eradication failure should be carried out
by testing for the presence of active infection (e.g. by histologic examination and culture, together with
an antibiotic-sensitivity test). The diagnosis of H. pylori infection in patients with a bleeding peptic
ulcer is limited by the decreased sensitivity of standard invasive tests; usually, both the RUT and
histologic testing should be performed during endoscopy and then combined with the UBT test.
Infection should be considered as present when any test is positive, whereas both the invasive tests
and the breath test should be negative to establish the absence of infection.
Treatment Approaches to Peptic Ulcer Disease
Eradication of H. Pylori Infection

Over the past 20 years, H. pylori eradication therapies have mainly consisted of antimicrobial agents
combined with antisecretory drugs. There is now a worldwide consensus that the first-line treatment
should be triple therapy with a PPI twice daily plus clarithromycin 500 mg twice daily and either
amoxicillin 1 g twice daily (PPI-CA) or metronidazole 500 mg twice daily (PPI-CM) for 7-14 days.[34]
Treatment with PPIs twice daily is superior to treatment once daily.[35] Successful eradication with first-
line treatments varies from 70%-95%, and 10-day and 14-day treatments are generally 7-9% more
effective than the most commonly used 7-day regimens.[36]
Poor compliance and bacterial resistance (depending on geographic location) can lead to treatment
failure, and therefore determine the choice of antibiotics used. Amoxicillin is favored over
metronidazole in first-line treatments because of the greater bacterial resistance to metronidazole and
the almost absent resistance to amoxicillin.[37] PPI-CA treatment is also preferred as a first-line
treatment over PPI-CM because of the concerns that treatment with PPI-CM will induce secondary
resistance to both clarithromycin and metronidazole, which are the most-effective treatment options.
Quadruple therapy with bismuth 120 mg four times daily, metronidazole 500 mg three times daily,
tetracycline 500 mg four times daily and a PPI twice daily for a minimum of 7 days has also gained
acceptance as a first-line treatment.[38]
As a guiding principle, summarized by an international panel of experts in the Maastricht Consensus

Report, second-line treatment is undertaken with a selection of antimicrobial drugs that differ to those
used in the first-line treatment since re-treatment with the initial regimen is not recommended.[34, 39]
Despite this careful approach, eradication can still fail, creating the need for additional pharmacologic
118
intervention. Subsequently, the choice of antibiotic therapy is guided by bacterial culture and the
selection of a third-line treatment prescribed according to microbial sensitivity to antibiotics.
H. pylori eradication rates are impacted by bacterial resistance and also by the pharmacogenetics
associated with individual PPIs. Polymorphisms of the CYP2C19 gene were reported to determine
how effective the antisecretory properties of PPIs are, with subsequent effects on H. pylori eradication
rates, suggesting that genotyping might be an effective tool to optimize eradication therapies.[40] A
recent meta-analysis that examined CYP2C19 polymorphisms and H. pylori eradication rates with PPI
first-line therapies, however, found that the eradication rates were comparable between patients with
the heterozygous-extensive-metabolizer genotype and those with the poor-metabolizer genotype, thus
lessening the clinical relevance of CYP2C19 polymorphisms.[41]
PPI-based triple therapies result in a markedly reduced ulcer recurrence rate of 12-14%, assessed
from 2 weeks onwards.[16] Earlier meta-analyses of H. pylori eradication reported recurrence rates of
2-3%,[42] and similarly, in complicated bleeding ulcers the recurrence rate after H. pylori eradication
ranged from 1.6-2.9%.[43] These studies confirm that H. pylori eradication provides a very effective
strategy for the management and reduction of peptic ulcer disease.
Studies indicate that eradication of infection sufficiently heals peptic ulcers in H. pylori-infected
individuals, and significantly reduces the ulcer recurrence rate, especially in patients who are not
taking NSAIDs or aspirin.[44] In a recent meta-analysis, prolonged therapy with a PPI after a course of
PPI-based 7-day triple therapy was not necessary for ulcer healing in H. pylori-infected patients.[45]
Some studies suggest that maintenance therapy with a PPI after eradication can significantly reduce
ulcer recurrence[46] and ulcer complications.[47] Maintenance treatment should be continued with a
PPI, following H. pylori eradication, in all patients who present with ulcer complications.
Management and Prevention of NSAID-associated Peptic Ulcer
In patients who continue to take NSAIDs, NSAID-associated duodenal ulcers heal after 4 weeks'
treatment with a PPI, and gastric ulcers after 6-8 weeks.[48] Co-therapy with a PPI reduces the risk of
developing a peptic ulcer in both acute (OR 0.70; 95% CI 0.24-2.04) and chronic (OR 0.32; 95% CI
0.15-0.67) elderly users of NSAIDs or aspirin.[49] Thus, it is advisable to give a PPI to symptomatic,
elderly patients who need an NSAID and/or aspirin.
The best ulcer-preventive strategy for patients who need to continue NSAID use is still debated.
Current strategies to reduce ulcer complications are not considered cost-effective in patients without
risk factors, but all are cost-effective in patients with a history of ulcer bleeding.[50] Misoprostol, a
mucosa-protective analog of prostaglandin E2, reduces the risk of ulcer complications, but only at the
recommended dose of 800 µg/day. Lower doses of misoprostol are not effective.[51] In a multicenter
trial of 535 H. pylori-uninfected patients with a history of gastric ulcers who required chronic NSAID
treatment, misoprostol 200 µg four times daily or lansoprazole 15 mg or 30 mg once daily all
significantly reduced gastric-ulcer recurrence (4%, 7% and 0%, respectively) compared with placebo
(65%) at 12 weeks.[52] Adverse effects were, however, higher in the misoprostol group.
Currently, studies suggest and guidelines recommend the careful selection of the right NSAID for the
right patient, based on individual risk assessment. Emphasis is placed, therefore, on the important
management strategy of defining those patients at risk (Box 1).[53] For patients with a history of
NSAID-associated ulcer bleeding who continue to require an NSAID and are not infected with H.
pylori, neither a coxib alone nor a PPI in addition to a nonselective NSAID can completely eliminate
ulcer recurrence. Indeed, in one clinical trial, ulcer recurrence and ulcer bleeding combined were as
high as 24% for a coxib alone and 32% for a PPI plus a nonselective NSAID.[54] To prevent ulcer
complications in a patient with a history of bleeding, a coxib combined with a PPI is, therefore, the
best approach (Box 1).[53, 55]
A new class of NSAIDs, the COX-inhibiting nitric-oxide donators, inhibit COX and simultaneously
donate nitric oxide to maintain mucosal blood flow. The first COX-inhibiting nitric-oxide donator
studied in a large clinical trial, AZD3582, was associated with significantly fewer erosions and ulcers
than naproxen in osteoarthritis patients.[56] A clinical trial in healthy volunteers also supports this
concept, where NCX-4016, a nitric-oxide-releasing derivative of aspirin, maintains COX1 and platelet
inhibitory activity while significantly decreasing gastrointestinal damage.[57] Another new class of
119
NSAIDs, the 5-lipoxygenase/COX inhibitors, which inhibit 5-lipoxygenase as well as COX1 and COX2,
has attracted interest. The gastrointestinal tolerability of licofelone, the first-studied drug of this class,
has been demonstrated in a study of healthy volunteers.[58]
Is H. pylori Eradication Necessary for Everyone During or Before NSAID Therapy?
Whether users of NSAIDs or low-dose aspirin should be routinely tested and treated for H. pylori
infection is still controversial.[59] Factors including the patient's ulcer risk, previous history of NSAID
use and their ongoing use of aspirin or NSAIDs should be considered (Box 2).[60] In one meta-analysis
of current NSAID users, the incidence of ulcer was not different between the H. pylori eradication and
control (PPI or placebo) groups.[61] Only two studies were included in this analysis, however, and the
sample sizes were small (n = 197 and n = 210, respectively), therefore a false-negative result could
not be excluded. A 'test and treat' strategy for H. pylori infection is not recommended for those already
on long-term NSAID therapy and who have a low or absent risk of peptic ulcer.[60] As treatment with a
PPI can worsen H. pylori-associated corpus gastritis, testing for and eradicating H. pylori infection
should be considered in long-term users of NSAIDs who have past or present ulcers before starting
long-term prophylaxis with PPIs.[62] Moreover, current guidelines recommend that H. pylori infection
should be eradicated in anyone in whom it is detected.[34, 63]
Meta-analysis suggests that eradication of H. pylori infection is significantly more effective for
preventing recurrent ulcer bleeding than antisecretory therapy alone, either with or without long-term
maintenance antisecretory therapy (1.6% versus 5.6%, and 2.9% versus 20%, respectively).[43] In
patients with ulcer bleeding related to long-term use of NSAIDs and/or low-dose aspirin, maintenance
antisecretory therapy should be combined with eradication of H. pylori to reduce the recurrence of
ulcer bleeding. As the antisecretory effect of PPIs is enhanced in the presence of H. pylori infection,
some prefer to undertake eradication therapy after the acute ulcer bleeding episode has been
successfully managed.
Use of low-dose aspirin in patients with H. pylori infection is a complex issue, because aspirin can
provoke bleeding from a pre-existing H. pylori-related ulcer by its topical injurious effects on the
gastric mucosa and its systemic antiplatelet effects. In patients starting aspirin, H. pylori eradication
prevents gastroduodenal mucosal injury.[64] Among H. pylori-infected patients with a history of ulcer
bleeding who were taking low-dose aspirin, eradication of H. pylori infection was comparable to PPI
treatment for preventing recurrent bleeding.[65] Eradication alone does not guarantee complete
protection: antisecretory therapy with a PPI in addition to confirmed H. pylori eradication significantly
reduced recurrent aspirin-related ulcer complications in long-term low-dose aspirin users.[47]
Eradication of H. pylori infection followed by antisecretory maintenance therapy can, therefore, reduce
ulcer rebleeding in long-term aspirin users, but more clinical trials are needed to explore the effect of
eradication on ulcer bleeding and rebleeding.
Ulcers and ulcer complications occur in former users of NSAIDs, and their risk remains higher than
baseline even after 1 year of non-exposure.[66]H. pylori infection is a known risk factor for ulcers in
both NSAID users and nonusers.[26] Switching from a nonselective NSAID to a coxib, therefore, does
not eliminate the risk of developing an ulcer and ulcer complications in patients with H. pylori infection,
although the risk is decreased in both infected and uninfected coxib users.[25]
Non-NSAID, Non-H. Pylori Ulcers
With the declining prevalence of H. pylori infection, some studies report an increased proportion of
non-NSAID, non-H. pylori ulcers, especially in the US.[67] In studies of more than 100 patients, up to
35% of duodenal-ulcer patients[68] and up to 34% of gastric-ulcer patients[69] had idiopathic ulcers. By
contrast, non-NSAID, non-H. pylori ulcers are rare in Asia, where H. pylori prevalence is high.[70] The
true prevalence of non-NSAID, non-H. pylori ulcers is unclear because it is not known whether the
prevalence is truly increasing or merely overestimated as a result of undetected NSAID use and/or
inaccurate diagnosis of H. pylori infection; similarly, the reported increase might be associated with
decreasing incidence or prevalence of H. pylori infection or a lower background ulcer rate.[6, 67] The
diagnosis of non-H. pylori, non-NSAID ulcers should be made only after careful exclusion of
surreptitious NSAID use and/or misdiagnosis of H. pylori infection. This process is aided by obtaining
a careful history, taking biopsies from several sites, use of more than one H. pylori diagnostic test,
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testing after stopping PPIs and antibiotic treatments, and by delaying tests in the case of a bleeding
ulcer.[67] Investigations should also exclude other uncommon causes of peptic ulcers.[6]
Much remains to be learned about non-H. pylori, non-NSAID ulcers. While the mechanism underlying
the development of non-H. pylori, non-NSAID ulcers is uncertain, acid hypersecretion, weakened
mucosal defense after H. pylori eradication, or other etiologic factors (e.g. diet and smoking status)
might play a role.[6] There are no randomized, controlled trials, but antisecretory therapy remains the
cornerstone of treatment to promote ulcer healing. Standard-dose PPI treatment should be prescribed
for 4 weeks in patients with duodenal ulcers and for 8 weeks in patients with gastric ulcers.[6]
Generally, patients respond well to these therapies, and no established evidence supports the need
for a longer duration or higher dose of antisecretory therapy in uncomplicated idiopathic ulcer alone,
although it might be required in a subset of patients. Nonresponders should, however, be investigated
for any possible underlying pathophysiology, such as a pathological acid hypersecretory state.[6]
Complicated Ulcer and Refractory Ulcer
For patients with a history of ulcer bleeding, treatment with a PPI significantly reduces the risk of
rebleeding and surgery.[71] Patients who have a history of bleeding or frequent ulcer recurrence should
be considered for maintenance PPI therapy. All patients with a history of ulcer bleeding should be
tested, and treated if infected with H. pylori.
Refractory ulcer—generally accepted to be a symptomatic, endoscopically proven ulcer greater than 5

mm in diameter that does not heal after treatment with a PPI (duration of PPI therapy is 6
weeks for duodenal ulcers or 8 weeks for gastric ulcer), or does not heal after a full dose of
H2RA (within 8 weeks for duodenal ulcers or 12 weeks for gastric ulcers)—is now rare.[72, 73]
For patients with a refractory ulcer, a careful search should be made for H. pylori infection,
surreptitious use of NSAIDs or an acid hypersecretory state such as Zollinger-Ellison
syndrome. Most ulcers will heal with 4-8 weeks of a standard-course PPI; in patients whose
ulcers are refractory to a standard dose of PPI, twice-daily dosing of the PPI treatment should
be prescribed for an additional 6-8 weeks.
Future Directions
In the past, H. pylori infection and the use of NSAIDs have dominated research into peptic ulcer
disease and have shaped its diagnosis and treatment. Even though H. pylori infection can be
successfully controlled with currently available pharmacologic approaches, there is still a serious need
for novel eradication monotherapies that will simplify treatment regimens, while improving eradication
rates.
Molecular techniques will continue to help us identify genetic factors that predict the development of
idiopathic ulcers. The identification of an H. pylori gene that promotes the development of duodenal
ulcers has introduced a novel marker that can identify patients at increased risk of duodenal ulcer
development and reduced risk for gastric atrophy and cancer.[74] The array of predisposing factors is,
however, predominantly host-oriented; that is, based on the genetic characteristics of the patient. The
existence of host-related differences in the physiology of acid secretion might lead to the identification
of genetic markers associated with peptic ulcer disease. Such markers might, in the future, help to
identify patients at high risk of or with susceptibility to peptic ulcer disease.
Conclusions
A search for H. pylori infection, the overt or surreptitious use of NSAIDs and the possibility of an acid
hypersecretory state are important considerations in the diagnosis of peptic ulcer and determine the
therapeutic approach. H. pylori eradication and/or antisecretory therapies are the mainstay of today's
treatment strategies. In the future, it is anticipated that advances in the fields of molecular biology and
genetic engineering will assist in the management of peptic ulcer disease. As the prevalence of peptic
ulcer disease increases with advancing age it is expected that this common disease will continue to
have a significant global impact on health-care delivery, health economics and the quality of life of
patients.
121
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123
Role of surgeon in acid peptic disease
Dr. T.K.Thusoo
Introduction:
Acid peptic disease includes a number of conditions whose patho-physiology is believed to be the
result of damage from acid and peptic activity in gastric secretion. Peptic Ulcer Disease (PUD) and
Gastro-Esophageal Reflux Disease (GERD) are the two most common and well defined disease
states included under the acid peptic disorders.
Surgical therapy for PUD has dramatically devolved since the advent of H-2 blockers and proton
pump inhibitors1. Identification and treatment of H. pylori infection in causation of PUD has further
resulted in significant decrease in elective surgery for acid peptic disorders. A little more than a
decade ago, the number of patients undergoing operation for complications of PUD appeared to be
relatively stable, although it is clear that the overall incidence of PUD had declined significantly2.While
few conclusive studies have been published, it has been a general perception that the number of
emergent operations has also decreased3.Elective surgery for PUD is nowadays unusual. This trend
has had a least two important consequences. Surgery for peptic ulcer disease is now typically
confined to the sickest and most high risk patients. In addition, surgeons today have considerably less
experience with the management of these problems and complex procedures such as parietal cell or
highly selective vagotomy4,5. Surgery may still be considered the mainstay for complicated PUD: long
history or failed medical therapy, gastric outlet obstruction, suspicion of malignancy or complication
such as perforation or bleeding6. The search has been for effective operations with few side effects or
long term sequalae7 The advent of H. pylori therapy has radically altered the role of surgery
particularly the frequency of its necessity. New technologies also have impacted on the role of
surgery. Endoscopic approaches to bleeding have obviated the need for some surgeries.
Laparascopic procedures have been proposed as an alternative to most open procedures8. At the
moment, there is no consensus concerning operative indication and specific procedures, which
requires individualization for each patient9.
Indications of Surgery
Indications for elective surgical treatment of PUD include patients refractory to medical treatment or
intractable PUD such as in Zollinger Ellison Syndrome and young patients who may face a life time of
acid inhibitory therapy. Issues of compliance, cost effectiveness and long term results may be
important factors in decision making.
Presently the role of surgery in PUD is limited essentially to complications such as bleeding,
perforation and post ulcer cicatrisation leading to pyloric stenosis or hour glass stomach.
Type of Surgery
Prior to the development of acid reducing medications and understanding the role of H. pylori in the
pathogenesis of PUD, acid reducing surgical procedures were generally considered to be standard
approach because of an unacceptably high ulcer recurrence without them. Non healing or recurrent
ulcers after adequate medical treatment may be an indication for definitive surgery which generally
involves an acid-reducing procedure such as vagotomy with or without drainage (as in highly selective
vagotomy) or partial gastrectomy10,11,12. However, such procedures have the potential to result in long
term adverse gastrointestinal sequelae such as diarrhea and dumping syndrome. Moreover,
recurrence after surgery has long been a problem, often requiring more aggressive surgery13.
Surgery for complications of PUD

Despite successful medical treatment to reduce acid hyper secretion and eradicate H. pylori, surgery
still plays an important role in the management of complicated PUD.
Bleeding Peptic Ulcer

It is recommended that a joint approach between physician / gastroenterologist and surgeon be
adopted in the management of bleeding duodenal ulcer. This is to reduce the morbidity and mortality
associated with delayed surgical intervention. Improvements in the endoscopic methods for the
control of hemorrhage from peptic ulcer has decreased the need for emergency surgery in such
124
patients. Endoscopic therapy (eg, thermal therapy and injection therapy) is indicated for active
bleeding or non bleeding visible vessel14 and can further decrease duration of hospitalization, reduce
the cost of treatment and improve mortality. Re-bleeding still reoccurs in 10-20% of endoscopically
treated patients. Whether repeat endoscopy or surgery is appropriate at this stage is unclear -
although salvage surgery after a second re-bleeding episode has a high mortality.
Early surgery should be considered in any one of these criteria:

a. Hypovolemic shock on admission( < 90mm Hg )
b. Age 65 yrs. or more
c. Resuscitation requirement of 4 or more units of blood in the first 24 hrs.
d. Signs of continuing bleeding
e. History of previous admission for ulcer complication
f. Ulcer size more than 2 cms. or with stigmata of recent haemorrhage ( despite endoscopic
haemostatic techniques )
g. Co-morbid factors
The majority of clinically significant bleeding ulcers are posterior ulcers..
The standard surgical procedure has been under running / suture ligation of the bleeding ulcer alone
or together with truncal vagotomy and pyloroplasty which is a safe and expedient option in the poor
risk patients15. Anterior ulcer may be excised and incorporated in the pyloroplasty. Four quadrant
suturing of the gastroduodenal artery, if involved, should be carried out. In the presence of a large
duodenal ulcer, partial gastrectomy is recommended for its lower risk of re-bleeding but there is
increased risk of duodenal leak compared to vagotomy and pyloroplasty. Whether, in the era of H.
pylori eradication therapy, simple suture is adequate surgical therapy is unclear. What is clear is that
both aggressive anti-secretory treatment with PPIs and antibiotics to eliminate H. pylori, decrease the
re-bleeding episodes and need for surgery, although perhaps not the mortality rates16. PPIs are more
effective than H2-receptor antagonists. Furthermore H. Pylori eradication therapy is more effective
than anti-secretory therapy alone in preventing re-bleeding17.
Perforation
The recommended surgical treatment for perforation is closure of perforation over an omental pedicle
with or without definitive acid reducing procedure. Controversy about the most appropriate operative
approach for acute perforation of duodenal ulcer has raged for many years. Simple suture or omental
patch closure is complicated by recurrent ulcer in one half or more of patients followed long-term. In
appropriately selected patients, acid-reducing operations such as proximal gastric vagotomy or truncal
vagotomy and drainage have been shown to reduce this proportion to about 10% without adding peri-
operative mortality or morbidity. While the data from randomized controlled trials have convincingly
demonstrated the efficacy of definitive operation in non geriatric stable patients, such an approach
has not been enthusiastically embraced nor widely practiced by most surgeons. Likewise,
laparoscopic simple closure and patching techniques are now being performed with increasing
frequency, but laparoscopic acid-reducing procedures are rarely practiced. Technical difficulty and
lack of learning opportunities make it unlikely that the majority of surgeons will soon become facile
enough with the laparoscopic definitive ulcer surgery to apply it competently. However, simple closure
without an acid – reducing procedure became feasible once it became evident that eradication of H.
pylori alone substantially reduced ulcer recurrence18,19,20. Clearly, if a patient‘s H. pylori status could
be determined prior to completion of the emergency operation, the most appropriate procedure would
be much more readily apparent. Unfortunately, this is seldom the case. Knowing that the antibiotic
regimen will fail in some 5% to 10% of infected patients at 1-year follow-up and that another 25% to
30% of patients may not be infected at all, offers limited assurance to the surgeon that he or she is
providing an optimal safety margin with simple closure alone. Furthermore, the availability of potent
acid suppressing drugs (such as PPIs) made long term medical therapy a reasonable option even in
patients without H. pylori. A strategy consisting of simple ulcer repair followed by combined
antibacterial and antisecretory drug therapy seems appropriate for the majority of patients18,21,22.
Reasonable exceptions to this approach may be patients who have previously failed an anti-H. pylori
regimen, have suffered other ulcer complications, have demonstrated dependency on chronic NSAID
therapy, or are known to be uninfected by H. pylori.
125
Obstruction
Chronic peptic ulcers in the pyloric region or duodenum may cause scarring which results in gastric
outlet obstruction. H. pylori eradication therapy is indicated early on in positive patients as resolution
has been reported23. Endoscopic dilatation may be a useful modality in some early cases. In all other
situations pyloric obstruction does need pyloroplasty or gastro-jejunostomy with vagotomy24.
Advent of laparoscopic surgery has been instrumental in changing the scenario of open operation with
the advantage of shortened hospital stay, decreased convalescence and early return to work, Almost
all types of conventional operations available for ulcer disease have been successfully performed by
laparoscopic approach and this has become the preferred approach in tertiary centers for operative
management of acid peptic disease25. Laparoscopic closure of perforated ulcer26,27, Laparoscopic
posterior truncal vagotomy with anterior proximal gastric vagotomy for refractory disease and
laparoscopic bilateral truncal vagotomy with stapled gastro-jejunostomy for obstructive disease have
become standard at some institutions25,28 and in times to come will become gold standard for surgical
management of peptic ulcer disease.
GERD
Gastro-esophageal reflux disease causes chronic symptoms due to lower esophageal mucosal
damage produced by the abnormal reflux of gastric contents into esophagus. This may or may not be
associated with hiatus hernia. The main stay of treatment is medical management with proton pump
inhibitors with or without prokinetic drugs. However, indefinite maintenance treatment using the full
healing dose is required to prevent relapse. This raises the issue of the role of surgery in the younger
patient. The prospect of a lifetime - several decades - of continuous acid suppression may be a less
attractive option than definitive surgery for GERD29. Most patients in older age groups will probably be
best treated with long-term omeprazole; the younger patient might be better served by surgery.
Surgery may be cost saving compared to PPI therapy in the long run30 .Definitive indications of
surgery are severe esophageal injury as manifested by ulceration, stricture, Barrett‘s mucosa,
incomplete resolution of symptoms or relapse while on medical treatment Fundoplication using 360°
or 270° wrap is recommended to prevent acid reflux into the esophagus . Open surgical fundoplication
techniques have been utilized successfully for over 40 years to restore the competence of gastro-
esophageal junction31.These techniques are effective, but substantial morbidity is associated with a
large upper abdominal incision, and poor access may culminate in splenic damage32. A Nissen
fundoplication, increasingly undertaken laparoscopically, is a reasonable alternative to prolonged acid
suppression. Fundoplication is a technique ideally suited for laparoscopic approach. Visualization of
esophago-gastric junction is generally better than in open operations, since the laparoscope can
access areas deep under the diaphragm that are not easily visualized at open operation. In addition,
the assistant may be able to facilitate the procedure instead of blindly retracting. The two procedures
which are most commonly performed laparoscopically for reflux are Nissen‘s (360° wrap) and Toupet
(270° wrap) procedures33. Early data from patients undergoing laparoscopic Nissen‘s procedures
have been good, with symptomatic relief in over 90 % of patients. In addition, a shortened hospital
stay, decreased convalescence, low rates of dysphagia and gas bloating syndrome have been
noted34,35,36. There is a negligible operative mortality, low morbidity rates and low failure rates37.
Patients need to be warned that they may be unable to belch or vomit after the operation.
Gastroenterologist on the other hand seem to be sceptical about the efficacy of laparoscopic anti
reflux surgery, claiming that too many variations of fundoplication are performed and complications
are blamed on one type of modification or another38,39. Recently endoscopic augmentation of LES
has been tried with encouraging results40.
Currently main risk in the choice of treatment for GERD could shift away from evidence based
medicine to vehemence based medicine, eloquence based medicine &/or business based medicine41.
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17. Gisbert JP, Khorrami S, Carballo F, Calvet X, Gene E, Dominguez-Munoz JE. H. pylori eradication therapy vs.
antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the
prevention of recurrent bleeding from peptic ulcer.[update of Cochrane Database Syst Rev. 2003;(4):CD004062;
PMID: 14584003]. [Review] [93 refs]. Cochrane Database of Systematic Reviews (2):CD004062, 2004.
18. Ng EK; Lam YH; Sung JJ; Yung MY;et al . Eradication of Helicobacter pylori prevents recurrence of ulcer after
simple closure of duodenal ulcer perforation: randomized controlled trial. Ann Surg 2000 Feb;231(2):153-8.
19. Datsis AC; Rogdakis A; Kekelos S; Zografos K; Sarantopoulou A; Spilliotis J :
20. Simple closure of chronic duodenal ulcer perforation in the era of Helicobacter pylori: an old procedure, today's
solution. Hepatogastroenterology 2003 Sep-Oct;50(53):1396-8.
21. Kate V; Ananthakrishnan N; Badrinath S : Effect of Helicobacter pylori eradication on the ulcer recurrence rate
after simple closure of perforated duodenal ulcer: retrospective and prospective randomized controlled studies.
Br J Surg 2001 Aug;88(8):1054-8.
22. Supanit Nivatvongs : Is there any role of acid reducing gastric surgery in peptic ulcer perforation. J Med Assoc
Thai : 2005; 88(Suppl 4) : S373-5.
23. Stabile, BE. Redefining the role of surgery for perforated duodenal ulcer in the Helicobacter pylori era. Ann Surg
2000; 231:159.
24. Gisbert JP, Pajares JM. Review article: Helicobacter pylori infection and gastric outlet obstruction - prevalence of
the infection and role of antimicrobial treatment. [Review] [29 refs]. Alimentary Pharmacology & Therapeutics
2002 ;16(7):1203-8.
25. Millat B, Fingerhut A, Borie F. Surgical treatment of complicated duodenal ulcers: controlled trials. [Review] [72
refs]. World Journal of Surgery 2000 ; 24(3):299-306.
26. Palanivelu C, Jani K, Rajan PS, et al : Laparoscopic management of acid peptic disease. Surg Laparosc Endosc
Percutan Tech. 2006 Oct; 16(5) : 312-6
27. Sanabria AE, Morales CH, Villegas MI. Laparoscopic repair for perforated peptic ulcer disease. [Review] [38 refs].
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28. Lunevicius R, Morkevicius M. Management strategies, early results, benefits, and risk factors of laparoscopic
repair of perforated peptic ulcer. [Review] [97 refs]. World Journal of Surgery 2005 ;29(10):1299-310.
29. Dubois F. New Surgical Strategy for gastro-duodenal ulcer : Laparoscopic approach. World J Surg . 2000; 24:270-
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30. Richard Smallwood. Aust Prescr 1995; 18: 97-99
31. Cookson R, Flood C , Koo B, et al. Short term cost effectiveness and long term cost analysis comparing
laparoscopic Nissen‘s Fundoplication with proton pump inhibitor maintenance for gastro-oesphageal reflux
disease. Br J Surg 2005; 92:700-06
32. Belsey R: Surgical treatment of hiatus hernia and reflux esophagitis. World J Surg 1977 ;1:421-423.
33. Spechler Sj and the Department of Veterans Affairs Gastroesophageal Reflux Disease Study Group: Comparison
of medical and surgical therapy for complicated gastroesophageal reflux disease in veterans. N Eng] j Med 1992
;326:786-92.
34. Toupet A: Technique d'oesophago-gastroplastie avec phrenogastropexie appliques dans la cure radicale des
hernies hiatales et comme complement de l'operation de Heller dans les cardiospasmes. Mem Acad Chir 89:394-
397, 1963.
35. Dallemagne B, Weerts JM, jehaes C, Markiewicz S, Lombard R: Laparoscopic Nissen fundoplication: Preliminary
report. Surg Laparosc Endosc 1:138-143, 1991.
36. Hinder RA, Filipi Cj: The technique of laparoscopic Nissen fundoplication. Surg Laparosc Endosc 1992 ; 2:265-72.
37. Cuschieri A, Shimi S, Nathanson LK: Laparoscopic reduction, crural repair, and fundoplication of large hiatal
hernia. Am J Surg 1992 ;163:425-30.
38. Granderath FA, Kamloz T, Schweiger UM et al. Long term results of laparoscopic anti reflux surgery , surgical
outcome and analysis of failure after 500 laparoscopic anti reflux procedures . Surg Endosc .2002; 16: 753-57.
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39. Kahrilas PJ . ―Laparoscopic anti reflux surgery: silver bullet or the emperor‘s new clothes ?‖ Am J Gastroentrol
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41. Richards WO, Houston HL, Torquati et al. Paradigm shift in management of GE reflux disease. Ann Surg 2003;
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42. Issacs D, Fitzgerald D. Seven alternatives to evidenced based surgery. BMJ 1999; 319:1618-19.
128
Surgery in Acute Pancreatitis
Dr. P.K.Mishra
Acute Pancreatitis is an inflammatory disease involving pancreas, adjoining tissues and remote
organs. It is a mild self limiting disease in about 80% of cases1. When severe it is a dreaded disease
in terms of morbidity and mortality2. Once pancreatic necrosis has started, there is no curative
medical or surgical treatment, till now, which could prevent or reverse the changes of pancreatitis.
Surgery is required in severe cases for dealing with local complications and preventing its recurrence.
Surgery in Acute Pancreatitis
1.Emergency Surgery
A. Infected necrosis
B. Hemorrhage
C. Colonic perforations
D. Pancreatic abscess
2.Elective Surgery
A. Pseudocyst
B. Pancreatic fistula, ascites
3. Surgery for prevention of recurrence

A. Cholecystectomy
Intestinal obstruction, ileostomy closure or incisional hernia may also be required to be tackled
surgically in the long term.
Although considerable experience has accumulated regarding management of this disease in the
published literature, there are differences in the patient profiles, disease severity, methods of
treatment which makes it difficult to give firm recommendations about many aspects of disease
management. There is paucity of randomized controlled trials thus rendering the level of evidences to
be tenuous. At G B Pant Hospital about 12-15 necrosectomies are done in a year and there is
cumulative experience of more than hundred and fifty necrosectomies. This write up is based on our
experience and more importantly, several excellent guidelines and reports of consensus conferences
recently published3-13. Definitions evolved in the Atlanta classification are used in this article.14
Surgery for Pancreatic Necrosis
Severe pancreatitis is accompanied by pancreatic necrosis. Necrotic tissue in the abdomen acts as a
reservoir of infection. If sepsis sets in, mortality is high. Identification of these patients and timely
intervention is crucial to improving survival. Critical questions regarding management of necrosis are:
1. Should necrosectomy be done? When?

2. Should sterile necrosis be operated upon?
3. What should be the method of necrosectomy?
4. Are minimally invasive methods adequate?
Most of the mortality in acute pancreatitis occurs in patients who have necrotizing pancreatitis. The
management is initially supportive with clinical and radiological staging and risk stratification. Rapidly
progressive multiorgan failure is seen in 10% of patients with 50-80% mortality. These patients often
have infected necrosis with generalized sepsis leading to multiorgan failure. Earlier reports suggested
that most of the deaths occurred after several weeks but recent literature shows it to be more evenly
distributed from the first week itself. It is suggested that severe pancreatitis develops in two phases.
First two weeks are characterized by systemic inflammatory response syndrome (SIRS) leading to
organ failures. Simultaneously, pancreatic necrosis is reaching its full extent. It gets infected over 2
weeks as the bacterial translocation occurs. Infection of pancreatic necrosis is seen in 30 -70% cases
of pancreatic necrosis15. Philosophy of management is maximal intensive care during the first two
weeks and aggressive debridement in the later phase. Early deaths are attributed to organ failures
while later deaths are due to complications of infected or sterile necrosis16-18.
129
Table 1. Mortality in Acute Pancreatitis12.
Median (%) Range (%)

All cases 5 2-9
Interstitial Pancreatitis 3 1-7
Necrotizing Pancreatitis 17 8-39
Sterile necrosis 12 2-44
Infected necrosis 30 14-62
Necrosectomy for infected necrosis
Rationale of surgery in necrotizing pancreatitis is removal of infected or potentially infected necrotic

material to prevent organ failure and septicaemia. When the necrotic material is already infected the
case for its removal is stronger. It is not easy to distinguish sterile from the infected necrosis.
Presence of gas in the necrotic material in the CT is an indication of infected necrosis. This is seen in
limited number of cases. Clinically, both types may have fever and leucocytosis. Organ failure is
higher in infected necrosis (62% vs. 45%) compared to sterile necrosis. Accordingly, CT or ultrasound
guided fine needle aspiration bacteriology (FNAB) with gram staining and culture is recommended in
the present literature. Initial aspiration should be performed in the second or third week of illness and
repeated weekly if negative and warranted. Aspiration should be done from both the centre and
periphery of the necrotic material as well as from the retroperitoneal areas of necrosis.
If the necrosis is infected, patient should be put on antibiotics and taken up for surgical debridement.
Literature is not very clear on the timing of this surgery. Probably it should be done promptly if the
patient is deteriorating or not improving. In case the patient is clinically stable, a prolonged course of
antibiotic may be tried as suggested by one review article. This gives time for the inflammatory
reaction to subside and purulent material to become organized for easier debridement. Against this
may be the fact that patient may deteriorate with the loss of the window period. More studies are,
therefore, required for a firm recommendation to be given on this aspect. In fact, even the concept of
surgical intervention has been challenged by a few reports which have achieved comparable mortality
with antibiotic treatment alone.
Treatment of sterile necrosis
Treatment of sterile necrosis is even more disputed. If pain and inability to take feeds persists beyond
two weeks, in a patient of pancreatitis with sterile necrosis, intervention may be required. Present
consensus is that these patients should be treated with supportive care for at least 2-3 weeks before
debridement. Early intervention increases the morbidity and mortality. It may infect the necrosis
requiring further interventions and increase in mortality. Delaying the intervention or avoiding it allows
the inflammatory process to settle down. Delayed interventions may allow for less formidable organ
preserving surgery. Organized necrosis may also be tackled with percutaneous or minimally invasive
techniques.
Surgical intervention
Surgical intervention requires organ preserving removal of pancreatic and peripancreatic necrotic
material. Since pancreatic inflammation may be ongoing, repeated interventions are required. Surgical
options after necrosectomy are:
1. Closed packing
2. Closed high volume lavage of lesser sac
3. Open drainage
4. Planned repeated necrosectomy with abdominal wall closure.
No randomized controlled trials comparing these procedures are available. These are believed to be
equally effective in skilled surgical centres. Although repeated laparotomies required in the last two
procedures reduce recurrent sepsis, incidence of intestinal fistulas, gastric outlet obstruction,
hemorrhage, and incisional hernia are increased. Mortality, though reduced in recent years remains
high. Most reports place it around 15-25%1.
130
Minimally invasive procedures
High mortality in surgical debridement especially in patients with organ failures has prompted
surgeons to look towards minimally invasive procedures. At present following have been tried:
1. Percutaneous Drainage (PCD)

2. Endoscopic transgastric procedures
3. Laparoscopic debridement
4. Retroperitoneal approach
Several studies have demonstrated usefulness and feasibility of these various approaches. These
require dedicated trained persons to achieve good results in selected cases. It is impossible to
compare these procedures with the ‗gold standard‘ of surgical debridement although many studies
have shown good results. Nevertheless, these procedures add to our armamentarium. They are very
useful to bridge over to a more stable state. They can be used as sole treatment in well localized
collection in a suitable site in a stable patient. Optimal management of these patients demands that
they be treated in a centre with a multidisciplinary approach with expertise in all specialties.
Cholecystectomy
Recurrence of gall stone pancreatitis has been reported in 29-63% of cases. Timing of
cholecystectomy has been debated over many years. Consensus evolved now is that patients with
mild pancreatitis should have laparoscopic cholecystectomy done during the same hospital stay
before discharge. In severe pancreatitis the cholecystectomy should be delayed till the resolution of
the inflammatory process. It can then be combined with intervention for pseudocyst avoiding multiple
procedures19,20. Cholecystectomy can be done during necrosectomy if the patient is stable and it can
be easily accomplished. For unfit, elderly patients endoscopic sphincterotomy is a valid alternative to
cholecystectomy21.
Pancreatic Abscess
Pancreatic abscess are seen in later course of the disease. These arise in less aggressive disease
where body defences are able to localize it. They may also arise as residual disease after
debridement. Percutaneous drainage is treatment of choice. If not feasible, surgical drainage gives
good results.
Hemorrhage
Serious hemorrhage complicates 1-3% of all cases of pancreatic necrosis and has bad prognosis22.
This may occur diffusely from the bed of necrosis, into gastrointestinal tract, into the pseudocyst,
peritoneum or retroperitoneal area. Pseudo aneurysm forms as a result of necrosis of the arterial wall
in the vicinity of pancreas due to proteolytic action of the enzymes. It may suddenly rupture with
severe life threatening hemorrhage. CT scan is able to detect the pseudoaneurysm in 80% of cases.
Angiography with its therapeutic capabilities, is however investigation of choice. Arterial embolization
can be done with definite haemostasis in 35-50% and good temporization in another 10-20% of
cases. Surgical ligation or packing is done for the remainder who continue to bleed1.
Pancreatic pseudocyst and fistula
Pancreatic pseudocyst, ascites or fistula arise due to ductal disruption in a patient of pancreatic
necrosis. Asymptomatic, small cysts (< 6 cms) can be managed conservatively. Larger symptomatic
cysts with ductal communication are managed with cysto-enterostomy. Pancreatic fistula from
peripheral leaks closes spontaneously. Central leaks are managed with stenting or internal drainage.
Again, the alternatives have not been compared in clinical trials. Local expertise usually governs the
practice.
Colonic perforations
131
Colonic perforation in a patient of pancreatic necrosis carries a grave prognosis. Surgical intervention
with diversion, debridement and feeding jejunostomy is urgently required.
References:
1. Werner J, Feuerbach S, Uhl W, et al. Management of acute pancreatitis: From surgery to interventional intensive
care. Gut 2005;54:426–36
2. Gallagher Scott F., Jaffray Colleen E., Murr Miche M. Acute Pancreatitis. In Charles J Yeo eds Shackelford‘s
Surgery of the Alimentary Tract Sixth edition Saunders, Philadelphia, 2007, pg 1296-1309
3. Banks PA. Practice guidelines in acute pancreatitis. Am J Gastroenterol 1997;92:377–86.
4. Uhl W, Warshaw A, Imrie C, et al. IAP guidelines for the surgical management of acute pancreatitis. Pancreatology
2002;2:565–73.
5. Werner J, Hartwig W, Uhl W, et al. Useful markers for predicting severity and monitoring progression of acute
pancreatitis. Pancreatology 2003;3:115–27.
6. Dervenis C, Johnson CD, Bassi C, et al. Diagnosis, objective assessment of severity, and management of acute
pancreatitis. Santorini consensus conference. Int J Pancreatol 1999;25:195–210.
7. Toouli J, Brooke-Smith M, Bassi C, et al. Guidelines for the management of acute pancreatitis. J Gastroenterol
Hepatol 2002;17(suppl):S15–39.
8. Bradley EL 3rd. Guiding the reluctant. A primer on guidelines in general and pancreatitis in particular.
Pancreatology 2003;3:139–43.
9. Sarr MG. IAP guidelines in acute pancreatitis. Dig Surg 2003;20:1–3.
10. Vege SS, Baron TH. Management of pancreatic necrosis in severe acute pancreatitis. Clin Gastroenterol Hepatol
2005;3:192–6.
11. Tenner S. Initial management of acute pancreatitis: Critical issues during the first 72 hours. Am J Gastroenterol
2004;99:2489–94.
12. Banks Peter A., Freeman Martin L., Practice parameter committee of the American college of Gastroenterology.
Practice Guidelines in Acute Pancreatitis. Am J Gastroenterol 2006;101:2379-2400.
13. UK working Party on Acute Pancreatitis. UK Guidelines for the management of acute pancreatitis. Gut 2005;54:1-9
14. Bradley EL 3rd. A clinically based classification system for acute pancreatitis. Summary of the International
Symposium on Acute Pancreatitis, Atlanta, GA, September 11through 13, 1992. Arch Surg 1993;128:586–90.
15. Baron HT, Morgan DE. Acute necrotizing pancreatitis. New Eng J Med 1999. 340;18:1412-7.
16. United Kingdom Guidelines for the management of acute pancreatitis. Gut 1998;42:1-13
17. Werner J, Uhl W, Buchler. Surgical treatment of acute pancreatitis.Curr treat options. Gastroenterol 2003;6::359-68
18. Hartwig W, Maksan S, Faitzik T, et al Reduction in mortalitywith delayed surgical therapy of severe pancreatitis.J
Gastrointestinal Surg 2002;6:481-7.
19. Uhl W, MuellerC, Krahenbul et al. Acute gall stone pancreatitis: timing of laparoscopic cholecystectomy in mild
and severe diseases. Surg Endosc 1999;13:1070-6.
20..Tang E, Stain S, Tang G et al. Timing of gall stone surgery in gall stone pancreatitis. Arch Surg 1995;130:496-9.
21. Uomo G, Manes G, Lacceiti M et al. Endoscopic sphincterotomy and recurrence of acute pancreatitisin gall stone
patients considered unfit for surgery. Pancreas 1997;14:28-31.
22. Stroud W, Cullom J, Anderson M. Hemorrhagic complications of severe pancreatitis. Surgery 1981;90:658-64.
132
Treatment options for Chronic Pancreatitis
http://www.medifocushealth.com/GS007/Understanding-Chronic-
Pancreatitis_Introduction-to-Chronic-Pancreatitis.php
Goals of Treatment for Chronic Pancreatitis
The goals of therapy for chronic pancreatitis (CP) are pain management, restoration of pancreatic
function, and the detection and management of complications. Treatment plans usually consist of
some or all of the following elements:
• Pain relief with medication, endoscopy, surgery, or nerve block

• Restoration of pancreatic function and nutritional status:
o supplementary pancreatic enzymes
o low fat diet/high carbohydrate diet
o supplements of vitamins and/or calcium, as needed
• Control of blood sugar if diabetes has developed
• Management of complications if they occur
• Total abstinence from alcohol and tobacco
The treatment of chronic pancreatitis depends on several factors such as the cause of the
pancreatitis, the extent and location of damage of the pancreas, the presence or absence of
symptoms, complications, and the general health of the patient. When symptoms are mild or absent
("silent pancreatitis") no treatment is indicated.
Medications for Chronic Pancreatitis
Pain is usually the most prominent symptom in chronic pancreatitis (CP) and is very difficult to control
in many patients. Due to the severity of pain which can be episodic or chronic and intractable, most
patients with chronic pancreatitis require some kind of pain medication. For milder pain, milder
analgesic medication such as Tylenol may be all that is necessary. However, if the pain is severe,
narcotics and even tranquilizers may be needed. Some pain medications can be administered through
skin patches (e.g., fentanyl) which provide a slow, steady release of the drug into the blood.
Dependence on narcotics is an issue for many patients with chronic pancreatitis.
Prednisone (a corticosteroid drug) in doses of 20 mg to 40 mg administered orally is effective in the

treatment of autoimmune pancreatitis.
Endoscopic Treatment for Chronic Pancreatitis
When pain control is not achieved with medical treatment, patients with chronic pancreatitis (CP) may
consider endoscopic surgery. The goal of endoscopy is to enhance the flow of pancreatic juice
through endoscopic procedures that may:
• Enlarge the pancreatic or bile duct opening

• Remove stones from the pancreatic or bile duct
• Place tubes or stents in the pancreatic duct to open ductal strictures
• Drain pseudocysts
The success rate for endoscopic procedures is between 60-80% by some estimates. Although there is
some controversy as to the long term efficacy of endoscopic treatment, a major advantage is that it is
not as invasive as open surgery, there is a shorter recovery period, and it is associated with fewer
complications.
133
Surgery for Chronic Pancreatitis
Surgery is performed on patients with chronic pancreatitis (CP) when more conservative therapies
have been exhausted. Sometimes, the patient is also in a situation where there may be a risk of
addiction to pain medication. The objective of surgery is to resect (remove) as little tissue as possible
in order to achieve improvement of symptoms, particularly disabling pain or flare-ups of pancreatitis.
Approximately 50% of patients with chronic pancreatitis undergo surgery at some point to either treat
complications or to manage pain. Surgery does not stop exocrine or endocrine loss of function.
Results of surgery indicate that 60-70% of patients find relief from surgery but after 5 years, the
benefits begin to diminish over time.
Surgical procedures are determined by the symptoms and their severity, in combination with the
location and extent of damage to the pancreas. Since pain is believed to be related to increased
pressure or tension in the pancreatic duct, creating an additional outlet for enhancing the pancreatic
flow, and thereby decreasing the tension, is an important part of most surgeries.
There are two types of surgical procedures that are considered for chronic pancreatitis:
• Pancreatic resection
• Total pancreatectomy (surgical removal of the pancreas) with islet cell transplantation
Pancreatic Resection
Pancreatic resection is performed with some of the following goals in mind:
• Pain relief
• Pancreatic drainage
• Maximizing whatever pancreatic function that can be salvaged
Pancreatic resection may be accomplished by a variety of different surgical techniques including:
• Puestow procedure - This is also called a lateral pancreaticojejunostomy in which the
pancreatic duct is connected to the small intestines so that pancreatic juices drain
directly into the intestines.
• Frey procedure - In this procedure, the Puestow procedure is combined with
removing part of the pancreatic head to improve pancreatic duct drainage. This
procedure may be performed if there is damage to the pancreatic head or if there is
enlargement of the pancreatic head.
• Beger procedure - Most of the pancreatic head is removed while sparing the
duodenum, stomach, and bile duct. This procedure may be performed to treat an
enlarged pancreatic head. This procedure is more commonly done in Europe but is
gaining favor in the US.
• Whipple procedure (pancreatoduodenectomy) - Classic pancreaticoduodenectomy in
which the head of the pancreas along with the small bowel embracing the head, the
gall bladder, and part of the bile duct and stomach are removed en-block. The
remaining part of the pancreas is connected to the small intestine. The modified
Pylorus-Preserving Pancreaticoduodenectomy preserves the entire stomach, the
pyloric sphincter, and maintains more normal gastric acid secretion and hormone
release, thus minimizing nutritional complications. Since pylorus preservation does
not seem to be associated with any consistent additional complications, pylorus
preservation is favored in most patients who undergo pancreaticoduodenectomy.
Pylorus preserving Whipple procedure has been the "gold standard" for chronic
pancreatitis surgery but newer techniques continue to develop which may be as
effective in regard to pain relief and optimization of remaining exocrine and endocrine
function.
• Distal Pancreatectomy - This procedure involves removal of the body and tail of the
pancreas. Because of the proximity of the tail to the spleen, damage in the tail may
be associated with splenic complication.
134
Total Pancreatectomy and Islet Cell Transplantation
Total pancreatectomy involves removal of the entire pancreas and may offer permanent symptom
relief. Since it is a more radical surgery and may involve significant complications, it is considered as
an option only when all other efforts have failed.
When the pancreas is removed, the patient may develop diabetes mellitus due to the loss of
pancreatic islet cells which produce insulin. In order to prevent this complication, the available insulin-
producing cells from the patient's pancreatic islet can be transplanted into the liver during the same
operation.
In five-year follow up studies, surgery appears to be superior to endoscopy for long term pain
reduction in patients with chronic pancreatitis. There are indications that partial or local resection of
the pancreatic head yield significant pain relief for most patients.
Celiac Plexus Neurolysis (Nerve Block) for Chronic Pancreatitis
As a last resort for patients with chronic pancreatitis (CP) who do not respond to other treatment,
nerve block, or paralyzing the pain conducting nerve center (celiac ganglion), may be performed. This
is usually achieved by injecting alcohol directly into the celiac ganglion under X-ray or ultrasound
guidance. This technique has not proven itself effective especially for young patients who have
undergone surgery.
Celiac block performed with the help of endoscopic ultrasound is a more recent advancement.
Doctors achieve nerve block with the use of steroids and/or local anesthetics which are safer than
alcohol. This procedure continues to undergo development.
The nerve fibers can be disconnected or cut during an operation, a procedure referred to as
Splanchenectomy or Splanchenic nerve block.
Restoration of Pancreatic Function and Nutritional Modifications for Chronic Pancreatitis
Many patients with chronic pancreatitis (CP) find that by taking pancreatic enzymes orally, they are
able to achieve improved digestive function. The enzymes, available in capsule form, should be taken
along with food. In addition, medication to decrease the acid production in the stomach should be
given along with these enzymes to prevent the destruction of the enzymes by acid.
Use of pancreatic enzymes also may reduce painful episodes and steatorrhea. There is still some
debate among doctors as to the efficacy of this treatment.
Some of the commercially available enzyme capsules are:
• Creon
• Pancrease
• Viokase
Nutrition is a significant issue for persons with pancreatitis. The combination of poor intake due to pain
and poor absorption carries a high risk of malnutrition. Patients with chronic pancreatitis often must
alter their food intake in order to optimize absorption of food and minimize pain associated with eating.
Towards this goal, patients may need to modify their diet to several small meals a day instead of three
large meals. The diet should be high in carbohydrate and low in fat to minimize the enzymes needed
for digestion.
If the patient is unable to eat, nutrition can be provided in a number of ways. A guiding principle of
nutrition is to use the digestive tract whenever possible to provide nutrition. Therefore, formula
feedings can be provided through a variety of tubes (nasojejunal, percutaneous endoscopic
gastrostomy, and surgical gastrostomy with jejunostomy) which enter the gastrointestinal tract and
maximize natural digestion. When this is not possible or if treatment involves total rest for the
digestive tract, total parenteral nutrition through a central venous line may be considered.
Peptamen is an elemental liquid diet that is being studied as an alternative source of nutrition while
avoiding abdominal discomfort in patients with pancreatic disease.
135
It is essential that persons with alcohol-induced chronic pancreatitis avoid further alcohol intake.
Control of Blood Sugar in Chronic Pancreatitis
It is important for patients with chronic pancreatitis (CP) to adhere closely to the recommendations of
a doctor regarding the development and management of diabetes.
Management of Complications of Chronic Pancreatitis
Complications are watched carefully and managed as they appear. Sometimes, surgical intervention
is necessary.
The Role of Complementary Medicine for Chronic Pancreatitis
Some doctors who believe that the pain in chronic pancreatitis (CP) is caused by free radical damage
suggest treatment with antioxidants (e.g., selenium, beta-carotene, or vitamins C and E). Studies with
small numbers of patients show promising results but further clinical trials are necessary. Some
patients have found relief from grape seed proanthocyanidin extract which is also an antioxidant.
It is important to notify your health care provider if you are using any alternative therapies, no matter
how insignificant or benign they may seem.
Psychosocial Considerations for Chronic Pancreatitis
Persons with alcohol-related pancreatitis are faced with the difficult task of abstaining from alcohol.
This requires a strong and structured support system. Substance abuse programs are widely
available and are a wonderful source of education and support to millions of people.
There are some patients for whom the pain of chronic pancreatitis (CP) is a major issue in their lives
and may disrupt daily activities and/or quality of life for them and for family members or friends. It is
important for these patients to consult with their doctor regarding pain clinics or support groups that
will help them cope as needed.
136
Choice of surgical procedures for chronic pancreatitis
PM Udani, V Purohit, P Desai, R D Bapat; R Satish R, C V Kantharia
Pain of chronic pancreatitis poses a therapeutic challenge. A conservative approach with replacement
enzyme therapy socio-economically burns out the patient. Drainage or resection with drainage
procedures are most ideal, however their indications differ according to ductal morphology. This
article reviews various surgical procedures proposed till date for relief of chronic pancreatic pain. It
gives a brief description of the procedure, highlights its indications and major adverse affects. It is
proposed to give insight to undergraduates, postgraduates as well as the practising surgeons about
the evolution of pancreatic surgery and guide them to the proper choice of procedure to adopt. There
is however always a gray zone wherein experience, patient‘s condition and available expertise dictate
the final procedure the patient undergoes.
INTRODUCTION
Chronic pancreatitis is defined as "a chronic inflammatory condition characterized by recurrent bouts
of acute exacerbation which eventually results in a defective restitution after acute pancreatitis"1. Pain
is the principle symptom although its exocrine / endocrine insufficiency is also equally important. A
number of procedures have been developed in the 20th century to deal with it. Literature review
indicates the maximum efficacy of any procedure upto date being 85-90%. There is no procedure
evolved so far to provide a 100% cure to this condition. This is probably due to the fact that chronic
pancreatitis is an ongoing process with multifactorial aetiology. The ideal procedure for treating pain in
chronic pancreatitis should be the one which is simple, easy to perform, associated with a low
morbidity / mortality rate and at the same time providing adequate drainage and not for augmenting its
endo / exocrine insufficiency. Surgeries for chronic pancreatitis can be broadly classified as:
A. Drainage procedures :
1. Partial : Draining the duct partially e.g. Duval, Puestow.
2. Complete : Consists of draining the main duct completely e.g. Partington‘s, Bapat‘s
B. Resectional procedure: Resecting a part of pancreas with adjoining organs : e.g. Whipples, Child‘s.
C. Extended drainage procedure: Adding a pancreatic sphincterotomy to the drainage procedure e.g.
Rumpf‘s.
D. Resection with extended drainage: A combination e.g. Beger‘s, Frey‘s.
The rationale for various procedures are :

•Drainage procedures were developed on the basis that pain in chronic pancreatitis is due to
ductal hypertension2 and proper drainage would decompress it.
•On the other hand, theory of perineural inflammation3 as the cause of pain led to development
of resectional procedures.
A. Drainage Procedures
It has been more than 3/4th of a century since these procedures were proposed4,5 Duval andZollinger6
first applied this principle. These procedures provide pain relief in upto 60-80% of cases.
I. Partial Drainage Procedures

1. Duval7 : Developed on the basis of presumption that a single stricture of duct of Wirsung
near the ampulla was responsible for the obstructive pathology and terminal drainage
would treat the condition. It consists of a distal pancreatectomy with splenectomy and
retrograde drainage of the main duct into a defunctioned jejunal loop (Fig. 1).
137
Fig 1 : Duval's procedure
2. Puestow - Gilesby Procedure8 : These authors demonstrated that multiple strictures (chain
- of - lake appearance) were the pathology involved in chronic pancreatitis. They
recommended a longitudinal opening of pancreatic duct from site of transection of the
pancreatic duct after resection of pancreatic tail and splenectomy, to a point just to the
right of mesenteric vessels and invagination of the open duct with pancreas into a Roux-
en-Y loop of jejunum (Fig. 2). This achieved wider drainage of the ductal system.
Fig 2 : Puestow - Gilesby Procedure

9
3. Leger‘s Procedure : Developed for distal stricture and consists of upto 40% distal
pancreatectomy with splenectomy and opening of pancreatic duct into a loop of jejunum
by a retrograde, lateral pancreatico jejunostomy (Fig. 3).
Fig 3 : Leger’s Procedure
4. Mercadier Procedure : For drainage of body of pancreas in Roux-en-Y Loop of jejunum by

a side to side anastomosis. (Fig. 4)
138
Fig 4 : Mercadier Procedure
Partial drainage procedures have been abandoned because of the small anastomosis which
soon tends to occlude. Also the concept of preservation of spleen with pancreatic tail is
important, as it prevents post-splenectomy sepsis10 and also delays the onset of Diabetes
Mellitus.11
II. Complete Drainage Procedures

1. Partington - Rochelle12 (1960) : Suggested a refinement in Puestow‘s procedure. A dilated
main pancreatic duct (minimum 8 mm) is a prerequisite for a good duct to mucosa
anastomosis, however people have even reported a mucosa to capsule anastomosis
when the duct size is 5 mm. It consists of a side to side, long, lateral
pancreaticojejunostomy without resection of pancreatic tail or spleen. (Fig. 5)
Fig 5 : Partington - Rochelle
2. Bapat‘s13 modification of Partingtons procedure :It consists of opening of the pancreatic

duct from head to tail with wide drainage by a side to end pancreaticojejunostomy after
fishmouthing the jejunal end to a required length. A duct to mucosa anastomosis is done.
A dilated duct of minimum 7 mm is a prerequisite. Advantages of procedure : Straight,
conical and dependent anastomosis, effective and complete drainage, more physiological
and only two suture lines involved (Fig. 6).
Fig 6 : Bapat's - procedure
139
B. Resectional Procedures
These procedures were resorted to when lesser procedures failed especially when
malignancy could not be ruled out.
1. Whipple‘s14 (1935) : Described by Allen O Whipple first in 1912, but published later for
malignant lesions of head of pancreas, now used for benign, inflammatory mass in head
of pancreas with a non dilated pancreatic duct. It consists of a pancreaticoduodenectomy
with reconstruction by a pancreatico - jejunostomy / gastrostomy + Gastrojejunostomy +
Choledochojejunostomy (Fig. 7). This is a complex, challenging technical exercise with
higher mortality rates as compared to a drainage procedure however with good results.
This procedure involves excising normal organs much against the principles of surgery for
a benign disorder and has led to more conservative approaches.
Fig 7 : Whipples procedure
2. Traverso - Longmire Procedure15 (1978) : It is a pylorus preserving pancreatico -

duodenectomy (Fig. 8). To overcome the problems of postgastrectomy syndrome
associated with classical Whipples, pylorus is preserved. Originally used for carcinoma of
head of pancreas, now also used for the head related sequelae of chronic pancreatitis.
Fig 8 : Traverso - Longmire Procedure
3. Warren‘s Denervated Pancreatic Flap16 (1984) : Here the pancreas is divided over the
portal - superior mesenteric vein after ligation ofsplenic artery and vein. The pancreatic
head is excised with a thin rim of residual pancreatic head. Remaining pancreas is not
drained. Ligation of spleenic artery and vein is presumed to denervate the gland.
4. Subtotal Pancreatic Resection : Consists of resection less than 80% of pancreas. Spleen
may be conserved. It is indicated when disease is confined to body and tail e.g.
pseudocyst, failed pancreaticojejunostomy, non dilated duct, pseudoaneurysm and when
it is not possible to rule out a malignant lesion in body and tail.
5. Child‘s Resection17 (1965) : It is a 95% distal pancreatectomy. First described by Barret

and Bowers18 in 1957, Child popularized it. The spleen, the tail, the body and the
uncinate process of pancreas are completely removed. A small cuff of head is preserved
along the lesser curvature of the duodenum, no more than 5% of the entire gland. This
cuff protects the vascularity and common bile duct during surgery. Not frequently done
and indicated when entire pancreas is uniformly and severely diseased and if previous or
lesser procedures have failed. Following this procedure the incidence of insulin
dependent diabetes mellitus rises upto 74% in non diabetics.
140
5. Total Pancreatectomy: Rarely indicated primarily as less radical procedure suffice. Indicated
secondarily after a pancreatico - duodenectomy or distal subtotal resection has failed to
provide pain relief. Duodenum preserving total pancreatectomy is also reported to be
effective. Since patients require insulin and also there are significant alteration in digestive
and absorptive function, 95%. Distal pancreatectomy is preferred which preserves normal GI
and biliary continuity.
Hypoglycaemic attacks after a Child‘s procedure or a total pancreatectomy can lead to death
or irreversible brain damage. However, there is a renewed interest for use of Whipples and its
variant the pylorus preserving procedures especially in cases of inflammatory pancreatic
mass with pain relief in upto 90% of cases with an acceptable morbidity (3.2%) and mortality
(3%) after an average follow up of 6.6 years.19
C. Extended Drainage Procedures
1. Rumpf‘s Extended Drainage20 : It is a combination of Partingtons with a transduodenal

pancreaticoplasty (Fig. 11). It is indicated when there is a prepapillary obstruction to the
drainage of pancreatic duct due to stones or stricture. With the advent of endoscopy, the
second half of the procedure has become unpopular.
Fig 11 : Rumpf’s Extended Drainage
D. Resection with extended drainage
As incidence of inflammatory mass in head of pancreas is about 30% of which only 10% are
malignant,21 resection with extended drainage provide cure in upto 94-95% of cases.22
1. Hans Beger‘s23 (1980) : It is a duodenum preserving resection of pancreatic head. Two

major steps are involved viz sub total resection of pancreatic head conserving the
duodenum and restitution of the exocrine pancreatic secretory flow. Resection: The
pancreas is transected at the border between the head and body above the superior
mesenteric vein, leaving a small disk of the head between the common bile duct and
duodenal wall. Drainage : Body is drained by an end to end pancreatico-jejunostomy and
by a side to side anastomosis to the rim of the resection cavity of pancreatic head, the
resection cavity is drained (Fig. 12).
Fig 11 : Hans Begers Drainage
141
This procedure is indicated in chronic pancreatitis with inflammatory mass in head with
medically intractable pain, obstruction of the common bile duct or duodenal stenosis.
Duodenum is preserved to maintain gastrointestinal hormones at physiologic levels and
also maintain intestinal continuity. Lately, the procedure has been extended to
encompass low grade pancreatic malignancies by Japanese.24,25
2. Extended Beger‘s : Performed in cases when there are multiple strictures in the left
pancreas with an inflammatory mass at pancreatic head. Here in addition to head
resection, a side to side anastomosis between the long incised main pancreatic duct and
interposed jejunal loop is performed (Fig. 13).
Fig 13 : Extended Hans Beger’s Procedure
3. Frey‘s Procedure26 (1987) : It is also a duodenum preserving procedure and comparatively

less technically demanding than Hans Beger. It involves coring out of pancreatic head
overlying the duct of Wirsung, Sartorini and uncinate process using a cautery, keeping at
least 5 mm pancreatic tissue posteriorly and medially along with opening the main duct in
body and tail. Drainage of the cored head with the opened main duct is by a lateral
pancreaticojejunostomy (Fig. 14). If duct is less than 8 mm in size : duct to capsule
anastomosis is performed. This procedure is indicated for pain in chronic pancreatitis with
its complications like a pseudocysts, common bile duct obstruction, pancreatic ascites,
fistulas and recurrent pain after a lateral pancreaticojejunostomy. It is contra indicated in
whom cancer cannot be ruled out, as it does not completely excise the head.27 Recently
Frey has even advocated his procedure for small duct upto 3.5 mm.28
Fig 14 : Frey’s Procedure
4. Izbicki‘s "V" Shaped Ventral Pancreatic Excision29 (1998) : Indicated for sclerosing ductal
pancreatitis (small duct disease) with maximum diameter of Wirsung duct less than 3 mm.
142
In this procedure, a long "V" shaped excision of ventral aspect of pancreas is done with a
lateral pancreaticojejunostomy by a mucosa to capsule anastomosis. (Fig. 15) This
procedure drains the main as well as second and third order ducts.
Fig 15 : Izbicki’s "V" Shaped Ventral Pancreatic

Excision
Duodenum preserving pancreatic head resection procedures are associated with less
morbidity, less incidence of pain, a greater weight gain with better glucose tolerance and
a higher insulin secreting capacity. Above all it leads to an early professional rehabilitation
as compared to a pylorus preserving pancreatico-duodenectomy. Also recurrence of pain
after a resectional with extended procedure is technical. This is due to insufficient
decompression of pancreatic gland in the "Achilles Heel Triangle" which is bounded by
common bile duct, hepatoduodenal ligament and wall of duodenum.
References
1. Kloepper G, Maillet B. Pathology of acute and chronic pancreatitis. Pancreas 1993; 8 : 659-70.
2. Ebbehoj N, Svendsen LB, Madsen P. Pancreatic tissue pressure in chronic obstructive pancreatitis. Scandinavian
Journal of Gastroenterology 1984; 19 : 1066-8.
3. Bockmann DE, Buechler M, Maltertheimer P, et al. Analysis of nerves in chronic pancreatitis. Gastroenterology
1988; 94 : 1459-69.
4. Coffey R. Pancreaticojejunostomy and pancreatostomy. Annals of Surgery 1909; 50 : 1238-64.
5. Link G. Treatment of chronic pancreatitis by pancreatostomy. Annals of Surgery 1911; 53 : 768-82.
6. Zollinger RM, Keith LM, Ellison EH. Pancreatitis.New England Journal of Medicine 1994; 251 : 497-502.
7. Duval MK. Caudal pancreatico jejunostomy for chronic relapsing pancreatitis. Annals of Surgery 1954; 140 : 775-85.
8. Puestow CB, Gillesby WT. Retrograde surgical drainage of pancreas for chronic pancreatitis. Archives of Surgery
1958; 76 : 898-906.
9. Leger L, Lenriot JP, Lemaigre G. Five to 25 year follow up after surgery for chronic pancreatitis in 148 patients.
Annals of Surgery 1974; 180 : 185-191.
10. Govil S, Imrie CG. Value of splenic preservation during distal pancreatectomy for chronic pancreatitis. British
Journal of Surgery 1999; 86 (7) : 895-8.
11. Wittingen J, Frey CF. Islet concentration in the head, body, tail and uncinate process of the pancreas. Annals of
Surgery 1974; 179 : 412-8.
12. Partington RF, Rochelle REL. Modified Puestow procedure for retrograde drainage of the pancreatic duct. Annals
of Surgery 1960; 152 : 1037-42.
13. Bapat RD, Jadhav RN, Mohite JD, Rohandia OS. Modified Partingtons procedure for pancreatico-jejunostomy in
chronic pancreatitis. Indian Journal of Gastroenterology 1997; 16 (3) : 122-5.
14. Augusto JB, Niederhuber JE. The pancreas. In Niederhuber JE, Dunwoody S Leditor. Fundamentals of surgery. 1st
Edition. Stamford : Appleton and Langue. 1998; 375-89.
15. Traverso LW, Longmire WP. Preservation of pylorus in pancreatico-duodenectomy. Surgery Gynecology
Obstetrics 1978; 156 : 954-62.
16. Warren WD, Millikan W Jr, Henderson JM, et al. A denervated pancreatic flap for control of chronic pain in
pancreatitis. Surgery Gynecology Obstetrics 1984; 159 : 581-6.
17. William JF, Charles G. Child 95% distal pancreatectomy for chronic pancreatitis. Annals of Surgery Oct., 1965; 162
(4) : 534=49.
18. Barret O, Bowers WF. Total pancreatectomy for chronic relapsing and calcinosis of the pancreas. USAF Medical
Journal 1957; 8 : 1037-41.
19. George HS, Michael BF, David MN, et al. Pancreaticoduodenectomy for chronic pancreatitis : Long term results in
105 patients. Archives of Surgery May, 2000; 135 : 517-24.
20. Rumpf KD, Pichlmayr R. Eine method zur chirurgischen behand lung der chronischen pankreatitis. Die
transduodenal pancreaticoplastik. Chirurg 1983; 54 : 722-7.
21. Maras WB, Helmut Friess, Michael W, et al. Randomized trial of duodenum preserving pancreatic head resection
versus pylorus preserving whipple in chronic pancreatitis. American Journal of Surgery 1995; 169 : 65-70.
22. Izbicki JR, Bloechle C, Knoefel WT, et al. Duodenum preserving resection of the head of pancreas in chronic
pancreatitis. Annals of Surgery 1995; 221 (4) : 350-8.
143
23. Beger HG, Witte C, Krautzberger W, et al. Erfahrung mit einer das duodenum erhaltenden pankreaskopfresektion
bei chronischer pancreatitis. Chirurg 1980; 51 : 303-7.
24. Amikura K, Tsai J, Akaishi S, et al. A case of mucin producing adenocarcinoma of the pancreas. Journal of
Japanese Pancreatic Society 1988; 3 : 52-7.
25. Yasuda H, Takada T, Uchiyama K, et al. Resection of the head of the pancreas with preservation of biliary tract and
duodenum. Journal of Biliary Tract and Pancreas 1990; 11 : 967-73.(Japanese)
26. Frey CF, Smith GJ. Description and rationale of a new operation for chronic pancreatitis. Pancreas 1987; 2 : 701-7.
27. Frey CF, Katsumi Amikura. Local resection of the head of pancreas combined with longitudinal pancreatico-
jejunostomy in the management of patients with chronic pancretitis. Annals of Surgery 1994; 220 (4) : 492-507.
28. Frey CF. The surgical management of chronic pancreatitis : The Frey procedure. Advances in surgery. 1999; 32 :
41-85.
29. Izbicki JR, Bloechle C, Knoefel WT, et al. Longitudinal V shaped excision of the ventral pancreas for small duct
disease in severe chronic pancreatitis. Annals of Surgery 1998; 227 (2) : 213-21.
144
Periampullary carcinoma: surgical management
Dr. Adarsh Chaudhary
Periampullary area is anatomically complex, representing the junction of three different epithelia,1-3.
the pancreatic, bile duct and duodenal mucosa. Tumors of periampullary region arise either at the
ampulla or near the ampulla. Macroscopically the epithelium of origin is often impossible to determine
but pathologically they can arise from the head of pancreas (60%), ampulla of Vater (20%); distal bile
duct (10%) and duodenum (10%). Because of the common location these tumor produces their
primary symptom of obstructive jaundice and are collectively classified as periampullary carcinomas.
Jaundice is most common presenting symptom (75%), 10% patients exhibit fluctuating jaundice.
Interestingly nonicteric patients appear to have more favourable prognosis, even compared stage for
stage with jaundiced patients. As a group nonicteric patients tend to have an earlier stage tumor and
more often have papillary tumor.4 Weight loss (70%), abdominal pain (62%), occult blood in stools
(45%), anemia (38%), anorexia (35%) and pancreatitis (5-20%) are other commonly reported
presentations of periampullary cancers.
The natural history of ampullary carcinoma is one of local invasion and subsequent distant
metastasis. The characteristic peritoneal spread of malignancy seen in cancer of pancreas is not
usually a feature of ampullary carcinoma. The goal of preoperative workup in patients with suspected
periampullary carcinoma is to establish the diagnosis with high degree of certainty and to assess
resectability. Several preoperative modalities have been suggested, these include computed
tomography (CT),5 magnetic resonance imaging,6 angiography,7 and endoscopic ultrasound (EUS).8
Using every modality in every patient is neither realistic nor cost effective. Radiological literature
describing the accuracy and sensitivity of these imaging modalities is difficult to interpret, because
patients with ampullary carcinoma are grouped with patients with carcinoma head of pancreas.
Ultrasonography is useful as initial investigation in patients presenting with evidence of biliary tract
obstruction. While it usually demonstrates a dilated common bile duct, it does not often detect a mass
in head of pancreas. The absence of pancreatic mass is an indirect evidence that patient may have
ampullary lesion. Unfortunately approximately 20% of pancreatic ultrasound evaluations are
technically inadequate because bowel gas or obesity.9
The use of thin section helical computerized tomographic scans (CT) has increased the sensitivity of
CT for detection and diagnosis of pancreatic cancer. But its utility in the diagnosis and assessment of
ampullary lesions has not been systematically evaluated to date.10,11 Most often CT demonstrates a
dilated common bile duct down to the level of duodenum, absence of pancreatic mass and
occasionally a mass at the ampulla. These features often helpful in differentiating ampullary or
periampullary neoplasm from a pancreatic tumor. Endoscopy is proved to be most accurate diagnostic
test, because it allows the direct visualization of ampulla of Vater and access for biopsy. Four distinct
types of appearance of ampulla may be seen on endoscopy namely a polypoidal tumor mass, an
ulcerating mass, an infiltrating mass and a normal ampulla. Polypoidal mass is most common finding
and has a better prognosis than ulcerating tumor.12 Most series reports that in 30-40% cases ampulla
may appear normal.13,14 These patients require sphincterotomy before the tumor can be visualized.
Recognition of tumor may be obscured endoscopically immediately after sphincterotomy, but is
usually evident at subsequent examinations, 10 days to 4 weeks later.12 Accuracy of biopsy for
diagnosis of malignancy has been shown to be related to the gross morphological characteristics of
the tumor,14 88% for ulcerating type, 64% for protruding type and 50% for intra-ampullary type.
Clinical decision making based on incomplete endoscopic removal of tissue must be done with care,
fully recognizing that carcinoma may be missed.
However, a consensus is lacking with regard to optimal imaging modalities in the evaluation of
patients with suspected periampullary tumors. Recently several studies have attempted to define a
role for endoscopic ultrasonography (EUS) for suspected periampullary tumors by comparing results
of endoscopic ultrasound and computed tomography with operative and pathologic findings. EUS has
been consistently shown to be superior than spiral CT for detection of small tumors.15-17 In
approximately 20% patients EUS can detect small periampullary lesions not detected by computed
tomography. Therefore, patients with smaller tumors undiagnosed by CT scanning would be a
candidates for improved detection by EUS.
145
TREATMENT AND RESULTS
At time of initial diagnosis of ampullary cancer Stage I disease is observed in about 10%, stage II
disease in 35%, Stage III disease in 45%, Stage IV disease in 10% of cases. Surgical treatment of
ampullary cancer has ranged from ampullectomy as described by William Halsted in 1899 to
pancreaticoduodenectomy. However, because of its remarkably less aggressive behaviour and a
better prognosis than the more common pancreatic carcinoma, indications for attempts at curative
resection should be more liberal and much broader than pancreatic ductal carcinoma. Ampulla of
Vater has distinct pattern of lymphatic drainage and in contrast to pancreatic tumors with a more
diffuse wide spread lymphatic spread, ampullary carcinoma tend to involve a single group of lymph
node near to the ampulla even in advanced cases. This tumor biology makes the ampullary
carcinoma a distinct clinical entity and probably in part explains the substantially superior prognosis of
these lesion if they do not infiltrate the pancreatic tissue
AMPULLECTOMY FOR PERIAMPULLARY CANCER
In patient with pT1 cancer, local resection by ampullectomy has been advocated by some
investigators as being equal to or better than pancreaticoduodenectomy. Ampulla of Vater has
distinct pattern of lymphatic drainage and in contrast to pancreatic tumors with a more diffuse wide
spread lymphatic spread, ampullary carcinoma tend to involve a single group of lymph node near to
the ampulla even in advance cases. This tumor biology makes the ampullary carcinoma a distinct
clinical entity and probably in part explains the substantially superior prognosis of these lesion if they
do not infiltrate the pancreatic tissue.
Some groups believe that local resection may be indicated in T1NoMo cancer (except high grade) or
adenoma containing focus of carcinoma in situ. If intraoperative findings show cancer more than T1
lesion, high grade tumor on frozen section evaluation after review of ampullectomy specimen and
lymphatic metastasis, these preclude resection and necessitate immediate
pancreaticoduodenectomy. A more difficult problem is when the pathologist defines a more advanced
lesion than was suspected preoperatively or Intraoperatively by review of permanent section in the
early postoperative period after completion of transduodenal ampullectomy. Most surgeons would
advocate pancreaticoduodenectomy to provide best chance for cure. Because of these uncertanities
most surgeons would recommend a pancreaticoduodenectomy for all resectable lesions.
Review of outcome after ampullectomy has revealed, tumor size was not a significant prognostic
factor for survival in few studies. The prognosis of patient even with invasion into the muscle of
sphincter of Oddi seems to be good provided there is no invasion into pancreatic parenchyma, or any
associated nodal metastasis.18-20 Based on their histopathological and clinical correlations. Hanyu et
al,21 have defined D0N0Pa0 as early carcinoma which is quite favourable for ampullectomy. Ultimately
the most Important factor for long term outcome are absence of invasion outside the sphincter of Oddi
(D0) and absence of nodal and lymphatic vessel invasion. After ampullectomy median survival is
around 24 months, with 5 years survival between 15 to 35%. Local recurrence and distant metastasis
is a major cause of treatment failure after ampullectomy
PANCREATICODUODENECTOMY
Today most surgeons consider pancreaticoduodenectomy as the procedure of choice in patients with
cancer of ampulla. As with local transduodenal resection, survival after pancreaticoduodenectomy is
determined by absence of lymph node metastases, the absence of invasion into pancreatic
parenchyma and ability to perform R0 resection. In most large series the chance for cure after
pancreaticoduodenectomy approaches to 50%.22 Median survival after R0 resection following
pancreaticoduodenectomy is about 45 months. In contrast median survival for periampullary
pancreatic ducal cancer following pancreaticoduodenectomy is about 16 to 18 months. This difference
in tumor biology justifies aggressive treatment and importance of differentiating ampullary from
pancreatic duct lesion preoperatively. Though most recent studies suggest 5 year survival more than
50%., 22 it is known that nearly 24% of 5 year survivors can subsequently died of recurrence.23 Willet
et al 24 described high incidence of both local (28%) and distant recurrence (44%) after resection.
Robertson et al 25 recently reported a high incidence of other malignant tumors in patient with
ampullary carcinoma and Nordback et al 26 described two cases of so called neoampullary carcinoma
arising at site of hepaticojejunostomy five and fifteen years after pancreaticoduodenectomy for cancer
146
of ampulla of Vater. Therefore, five year disease free survival is not a guarantee of cure and life long
follow up is advisable after resection for periampullary carcinoma.
POST OPERATIVE ADJUVANT THERAPY
Data supporting use of adjuvant therapy in periampullary carcinoma is limited. Inclusion of patients
with ampullary cancer when analyzing result of pancreatic cancer is inappropriate because two
conditions do not have a similar prognosis. Splinter et al27 in a trial of adjuvant combination
chemotherapy for ampullary carcinoma showed poor patient tolerance of treatment and no survival
benefit compared with historical controls. Willet et al 24 described a trend towards better local control
( 83% Vs 50%) in 12 of 29 patients with high risk pathological features (tumor invading the pancreas,
poorly differentiated histology, positive lymph nodes, positive resection margins) who received post
operative irradiation after pancreaticoduodenectomy, but there was no improvement in survival.
Major criticism of these clinical studies is the lack of randomization and small number of patients. A
Norwegian multicentre randomized trial,28 involving 14 patients with ampullary carcinoma
demonstrated that adjuvant chemotherapy reduces the incidence of recurrence at least in the first 2
years after resection but an increased cure rate was not observed. So currently there is no data
supporting the use of postoperative chemotherapy or radiation therapy in an adjuvant setting.
References
1. Anderson JB, Cooper MJ, Williamson RCN. Adenocarcinoma of the extrahepatic biliary tree. Ann R Coll Surg
Engl. 1985;67; 39-43.
2. Dawson PJ, Connolly MM. Influence of site or origin and mucin production on survival in ampullary cancer. Ann
Surg. 1989;210:173-179.
3. Blumgart LH, Kennedy A. Carcinoma of the ampulla of Vater and duodenum. Br J Surg. 1973;60:30-40.
4. Yamaguchi K, Enjoji M, Kitamura K. Non-icteric ampullary carcinoma with a favorable prognosis. Am J
Gastroenterol 1990;85(8): 994-999.
5. Bluemke DA, Cameron JL, Hruban RH, et al. Potentially resectable pancreatic adenocarcinoma ; spiral CT
assessment with surgical and pathologic correlation. Radiology. 1995;197:381-385.
6. Muller MF, Meyenberger C, Bertschinger P, et al. Pancreatic tumors: evaluation with endoscopic US, CT, and MR
Imaging. Radiology 1994;190: 745-751.
7. Dooley WC, Cameron JL, Pitt HA, et al. Is preoperative angiography useful in patients with periampullary tumors.
Ann Surg. 1990;211:649-655.
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9. Brambs HJ, Claussen CD. Pancreatic and ampullary carcinoma: ultrasound, computed tomography, magnetic
resonance imaging and angiography. Endoscopy 1993;25:58-68.
10. Gulliver DJ, Baker Me, Cheng Ca, Meyers WC, Pappas TN. Malignant biliary obstruction; efficacy of thin-section
dynamic CT in determining resectability. Am J Roentgenol 1992;159: 503-507.
11. Balthazar E, Chako A. Computed tomography of pancreatic masses. Am J Gastroenterol 1990;85;343-349.
12. Monge JJ, Judd ES, Gage RP. Radical pancreatoduodenectomy: a 22 year experience with the complications,
mortality rate and survival rate. Arch Surg 1964;160:711-722.
13. Hayes DH, Bolton JS, Willis GW, Bowen JC. Carcinoma of the ampulla of Vater. Ann Surg 1987;205 :572-577,
14. Yamaguchi K. Enjoji M, Kitamura K. Endoscopic biopsy has limited accuracy in diagnosis of ampullary tumors.
Gastrointest Endosc 1990;36 (6):588-592.
15. Bluemke DA, Cameron JL, Hruban RH, et al. Potentially resectable pancreatic adenocarcinoma: spiral CT
assessment with surgical and pathologic correlation. Radiology. 1995;197:381-385.
16. Muller MF, Meyenberger C, Bertschinger P, et al. Pancreatic tumors: evaluation with endoscopic US, CT, and MR
imaging. Radiology. 1994;190745-751.
17. Rooley WC, Cameron JL, Pitt HA, et al. Is preoperative angiography useful in patients with periampullary tumors.
Ann Surg 1990;211:649-655.
18. Tara RY, Hermann RE, Vogt DP. Results of surgical treatment of periampullary tumors: a 35-year experience.
Surgery 1986;100:716-723.
19. Goldberg M, Zamir O, Hadary Y, Nissan S. Wide local excision as an alternative treatment for periampullary
carcinoma. Am J Gastroenterol 1987;82:1169-1171.
20. Klein P, Reingruber B, Kartl S, Dvorak O, Hohenberger W. Is local excision of pT1-ampullary carcinomas justified?
Eur J Surg Oncol 1996;22:366-371.
21. Hanyu F, Imaizumi T, Nakamura M. Yoshikawa I. Proposed definition of early cancer of the papilla of Vater. Tan to
Sui (J Bil Pancr) 1984;55:847-852.
22. Kawarada Y, Takahashi K, Takata M, Isaji M, Ogura Y, Mizumota R. Surgical treatment of carcinoma of the papilla
of Vater. J Hep Bil Pancr Surg 1993;1:8-13.
23. Monson JR, Donohue JH, McEntee GP, et al. Radical resection for carcinoma of the ampulla of Vater. Arch Surg
1991;126:353-357.
24. Willet CG, Warshaw AL, Convery K, Compton CC. Patterns of failure after pancreaticoduodenectomy for
ampullary carcinoma. Surg Gynecol Obstet 1993;176:33-38.
25. Robertson JFR, Boyle P, Imrie CW. Patients with ampullary carcinoma are prone to other malignant tumours. Br J
Cancer 1988;58:216-218.
147
26. Nordback IH. Hruban RH. Cameron JL. Second primary lesions in the biliary tree after successful resection of
ampullary carcinoma. Surgery 1992;112:111-115.
27. Splinter TAW, Obertop H, Kok TC. Jeckel J. Adjuvant chemotherapy after resection of adenocarcinoma of the
periampullary region and head of the pancreas. J Cancer Res Clin Oncol. 1989;115-200-202.
28. Bakkevold KE, Arnesjo B, Dahl O, Kambestad B. Adjuvant combination chemotherapy (AMP) following radical
resection of carcinoma of the pancreas and papilla of Vater. Results of a controlled, prospective, randomised
multicentre study. Eur J Cancer 1993; 29A: 698-703.
148
Laparoscopic Management of Pancreatic Diseases
The laparoscopic management of pancreatic disease is one of the most challenging in laparoscopic
surgery. This is especially true when considering that of pancreatic resection. Well-trained
laparoscopic surgeons have found that operating on the pancreas, like virtually all intra-abdominal
procedures, is technically feasible. Laparoscopic principles suggest that the patient will probably
benefit from less postoperative pain, improved wound cosmetics, quicker return to routine activities,
and shorter hospital stay. Ultimately the acceptance of many laparoscopic operations will be
determined by their degree of difficulty, the operating time, the cost (both hospital and societal), and
patient outcomes.
In comparison with the literature available on other laparoscopic operations, the information available
on pancreatic resection is too scant to draw firm conclusions. However, leaders in the field have
demonstrated that pancreatic resection is feasible, and are carefully examining their outcomes to
further elucidate the role of this technically demanding procedure.
Laparoscopic procedures for the pancreas fall into four main categories:
1. Laparoscopic staging of pancreatic malignancy
2. Bilioenteric or gastroenteric bypass
3. Pancreatic resection, and
4. Management of pancreatic pseudocysts
Anatomic considerations
The majority of the pancreas lies in a retro peritoneal position, transversely oriented from the second
and third portions of the duodenum to the hilum of the spleen. Anterior access to the gland (body and
tail) is readily obtained by division of the gastro colic omentum. This division may be performed by
electrocautery, multiple individual clip applications or vascular stapling devices, or ultrasonic
dissection.
Access may be obtained through the gastrohepatic ligament, although the exposure is usually less
adequate. The patient is positioned in a slight head-up position to allow gravity retraction of the
viscera. An oblique angle (30° or 45°) telescope is necessary for adequate visualization. Laparoscopic
ultrasound is proving to be an essential tool for many aspects of pancreatic surgery.
Laparoscopic staging of pancreatic malignancy
Patients with pancreatic malignancy generally present at later stages of disease. Frequently the
disease is unresectable due to tumor size or tumor metastases by the time symptoms occur. Surgical
resection for pancreatic cancer still offers the only reasonable chance at a cure. Historically; many
patients underwent unnecessary laparotomy in an effort to assess resectability. CT scans have
helped many patients avoid the morbidity of a non therapeutic laparotomy. However, even with this
modality, unresectability rates at laparotomy can approach 60%. This is most often due to the
presence of unrecognized peritoneal metastases (<1 cm) and tumor invasion not appreciated on CT
scan. Spiral CT and magnetic resonance imaging (MRI) are more reliable for predicting
unresectability, but are still not adequate in our opinion. In a large multicenter study, Megibow and
coworkers reported a sensitivity of 77%, a specificity of 50%, and an overall accuracy of 73% for
dynamic CT scanning. Also in their study, they found no additional benefit from MRI.
Diagnostic laparoscopy further narrows patient selection for therapeutic laparotomy. Warshaw and
coworkers found that an additional 35% of patients could avoid laparotomy with the use of diagnostic
laparoscopy. Despite improving non-invasive imaging methods since Warshaw and coworker's early
reports, more recent studies confirm Warshaw and co-worker‘s initial findings that a significantly
number of patients (22% to 35%) can avoid laparotomy with the use of staging laparoscopy.
Further, the sensitivity for evaluation of unresectable disease appears further enhanced with the
addition of the laparoscopic ultrasound to the laparoscopic staging procedure. Callery and coworkers
use a multifrequency laparoscopic ultrasound probe to search for occult metastases and assess
posterior invasion into vascular structures like the portal vein. Tumors other than pancreatic were
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included. Fifty patients were referred for staging laparoscopy after interpretation of conventional
noninvasive imaging modalities had determined the tumor to be resectable. Laparoscopic ultrasound
established unresectability in 11 patients (22%) in whom staging laparoscopy alone was negative. In
another study by John and coworkers involving 40 consecutive patients with pancreatic cancer
presenting for diagnostic laparoscopy, laparoscopic ultrasound found an additional 25% (10 patients)
whose disease was unresectable when compared with laparoscopy alone. They found the use of
ultrasound significantly improved specificity and accuracy as compared with laparoscopy alone (88%
and 81 % vs 50% and 60%, respectively).
Staging laparoscopy technique
Patients generally undergo staging laparoscopy on the same day they are scheduled for resection.
Patients are placed in the supine position on an electrically equipped bed (preferably). A 10-mm trocar
is placed in the infraumbilical position to serve as the camera port. The abdomen is insufflated to 15
mm Hg. A 30° laparoscope is used. A second port of 5 mm is placed in the right midclavicular line
several centimeters from the subcostal margin. A four-quadrant exploration is then carried out.
Grasping devices, biopsy forceps, or electrocautery instruments may be alternatively introduced
through the 5-mm port. Important peritoneal surfaces to visualize for areas of metastases include the
undersurface of abdomen including falciform, diaphragm, and liver. The omentum must be examined
thoroughly and when possible retracted superiorly to evaluate the base of the transverse colon, its
mesentery, and the ligament of Treitz (this may require an additional port).
If there is evidence of unresectability, the procedure is terminated. Otherwise laparoscopic ultrasound

is carried out. A second 10 mm port is placed in the right midclavicular line at the level of the
umbilicus. Laparoscopic ultrasound is then performed using a 9 mm in diameter linear array 7.5-MHz
contact ultrasound probe with Doppler flow capability. The liver is systematically scanned (anterior,
lateral, inferior) at penetration depths of 7 cm for evidence of metastatic spread or extent of primary
tumour invasion. Frequently; biliary and pancreatic metastases to the liver have a characteristic bulls-
eye appearance with an echoic rim encircling a mixed-echo tumour center. If found, biopsy for such
lesions may be attempted percutaneously with laparoscopic ultrasound guidance.
Attention is then turned to ultrasonic evaluation of the portahepatic, peripancreatic, para-aortic, and
celiac axis for evidence of nodal disease. Lymph nodes greater than 10 mm may be biopsied.
Laparoscopic ultrasound with Doppler flow capability is then used to help locate and assess the
potential for tumor extension to surrounding peripancreatic vascular structures (primarily portal vein,
but also superior mesenteric vein and artery, and celiac axis).
Bilioenteric or gastroenteric anastomosis for pancreatic malignancy
Unresectable patients might be candidates for biliary or enteric bypass. The risk and benefits of
bypass must be weighed against existing palliative options, the patient's condition, existing or
impending obstruction, and expected length of survival based on tumor burden. For most patients with
unresectable disease, life expectancy can be expected to be less than 1 year. Proper management
tailored to the individual patient's needs is important so as to offer as much quality of life free from
hospitalization as possible.
Commonly; patients will present with some degree of biliary obstruction or will suffer from it during the
course of the disease. Most patients with obstructive jaundice are best treated by placing an
endoscopic or percutaneous stent. The success rate is high (85%), with a low associated mortality
(1% to 2%). Studies comparing open bypass with those stented endoscopically for obstructive
jaundice found no advantage to the surgical approach. Morbidity from stent placement includes
potentially frequent admission to hospital (occlusion, infection) and significant cost for endoscopic
retrograde cholangiopancreatography (ERCP) and stent. However, repeat placement has become
less necessary with the use of improved techniques and stent design. Patients may present or
develop distorted duodenal anatomy that makes initial or subsequent stent placement impossible.
This finding may be coupled with gastric outlet obstruction. In these patients, bypass procedures may
be offered after evaluation of surgical risk or life expectancy.
The morbidity of open surgical bypass is substantial (19%). Laparoscopic biliary

(cholecystojejunostomy) or gastric bypass (gastrojejunostomy) is feasible. There is potential for
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shorter recovery, shorter return to activity; and low morbidity, as evident in several small studies. We
favor an approach, as suggested by Nathanson, that the bypass should be reserved for a later date
from the diagnostic laparoscopy at such time when duodenal obstruction precludes repeat stent or
there is stent failure (blockage, recurrent sepsis). For the stomach, failure would include when
symptoms of gastric outlet arise. Conditions at initial laparoscopy that might argue for immediate
bypass include inability to stent the biliary system in the preoperative setting, endoscopic or radiologic
evidence of impending duodenal obstruction, or laparoscopic impression of large locally advanced
mass with minimal to no evidence of metastatic spread.
Biliary and gastric bypass
Cholecystojejunostomy may be carried out if the gallbladder is present and suitable for anastomosis,
and the cystic duct is patent and its junction to the common bile duct (CBD) is far from the tumor.
Frequently this information is available by preoperative imaging studies (ERCP or percutaneous
transluminal cholangiography). If not, patency of cystic duct and its relation to primary tumour location
may be obtained by performing a cholangiogram after cannulation of the gallbladder. Similarly,
laparoscopic ultrasound may be used for such an assessment.
For either anastomosis, patients are positioned supine and the port placement is the same. A 10-mm
trocar is placed at the inferior umbilical region and a 30° telescope is used. Additional ports and
operating room personnel are positioned.
The omentum and transverse colon are elevated with instruments introduced through the epigastric
and either 12-mm port. The small bowel is traced back to the ligament of Treitz. A loop of small bowel
is then chosen that will comfortably reach stomach and gallbladder without tension (note that this is
true once the transverse colon and omentum are allowed to return to normal position). For the biliary
bypass, a cholecystotomy is performed with electrocautery on the gallbladder fundus. The biliary
contents are then aspirated. An enterotomy is performed on the antimesenteric surface of the chosen
small bowel loop. A 30 mm endoscopic stapler is introduced through the right 12-mm port. The jaws of
the stapler are opened and one arm of the stapler is inserted into the enterotomy. The jaws of the
stapler are then closed to function as a large grasper. The stapler and small bowel contained within
are then maneuvered adjacent to the cholecystotomy. The jaws of the stapler are opened again and
the free arm of the stapler maneuvered into the cholecystotomy. Assistance is provide by a blunt
grasping instrument inserted through the additional ports (epigastric). After proper alignment is
assured, the stapler is fired to complete the anastomosis. The original sites may be closed with
additional firings of the stapler. At this point the endoscopic stapler will be introduced through the left
12-mm port. Care must be taken not to narrow the anastomosis or the lumen of the small bowel
significantly.
To fashion the gastric bypass, a dependent site is chosen along the greater curvature. The gastrocolic
omentum is divided close to the greater curve within the gastroepiploic arcade for a distance of
approximately 3 to 4 cm with the ultrasonic scalpel or by electrocautery. A gastrotomy is made on the
greater curvature. The anastomosis will be formed along the greater curve but will extend into the
posterior wall of the stomach. Typically, the stapled anastomosis will be created by introducing the
stapler through the right 12-mm port. The anastomosis should consist of two firings of the 30-mm
endoscopic linear cutter.
Ideally, the stapled anastomosis should be aligned to cross the greater curvature to the posterior
surface (ie, through the area of divided gastrocolic omentum). If fashioned in this way, the original
puncture sites will be easier to close and the anastomosis more dependent.
Laparoscopic pancreatic resection
Indications for complete or partial pancreatic resection include:

1. Aadenocarcinoma
2. Insulinoma (neuroendocrine) and
3. Chronic pancreatitis
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Improved technique and postoperative care have rendered morbidity and mortality for pancreatic
resection, including Whipple's procedure, to less than 5%. Laparoscopic techniques could potentially
lower this rate even more or at least afford less pain and a more rapid recovery.
Laparoscopic Whipple's procedure was first carried out by Gagner in a small series of three patients
with various diseases (pancreatitis, ampullary cancer, adenocarcinoma). He subsequently has
reported on a pylorus-preserving technique performed in one patient with pancreatitis. The initial
experience indicates that it is technically feasible, but because of its operative time, complexity, and
as yet no demonstrated improvement in outcome, this procedure must be considered investigational.
Hand-assisted laparoscopic surgery may make pancreatic resection more practical.
Laparoscopic pancreatic procedures involving distal pancreatectomy appear to hold more promise at
present. Soper and co-workers reported success with his technique in the pig model. Gagner and
coworkers successfully performed distal pancreatectomy for a variety of disease processes including
islet cell tumours, cystadenocarcinoma, and pseudocyst. The spleen was preserved in all cases and
operating times ranged from 2.5 to 5 hours. Cases were managed with the patient in the left lateral
position, with pancreatic division carried out with a 60-mm linear cutter. Others are reporting initial
success with distal resection.
Laparoscopic management of pancreatic pseudocyst

Pancreatic pseudocysts may be defined as a collection of pancreatic secretions, serous fluid, or
necrotic debris surrounded by a nonepithelialized wall made up of granulation tissue and variable
degrees of fibrous tissue. Pancreatic pseudocysts must be distinguished from true cysts of the
pancreas, which are characterized histologically by the presence of an epithelial lining. Pseudocyst
formation is the result of a post inflammatory process arising from patients with acute or chronic
pancreatitis. An understanding of the natural history of pancreatic pseudocyst is important when
deciding on invasive therapy versus expectant management. Studies like those by Bradley and
coworkers had a great influence in the management of pseudocystic disease. Bradley and coworkers
suggested the likelihood of regression diminished and the likelihood of complications rose
dramatically after a 6-week period. More recent data suggest that this patient population may be
watched safely for longer periods. Yeo and coworkers followed asymptomatic patients with
pseudocysts by CT scanning for 1 year (48% were successfully observed with only a 2.7%
complication rate). The only predictor for intervention was size greater than 7.4 +_0.6 cm.
General asymptomatic patients with pancreatic pseudocyst may be followed up for extended periods
of time. This conservative approach is more likely to be successful in patients with small 6 cm
pseudocysts. Other options are available for drainage procedures (eg, percutaneous transgastric,
ERCP).
Laparoscopic pseudocyst drainage

Preoperative decision making and subsequent laparoscopic operative approach should mimic that of
open operative planning. The selection of procedure will depend on the anatomic location of the
pseudocyst, pseudocyst size, and associated pancreatic duct or distal common bile duct
abnormalities.
Reports by Newell and coworkers document that pseudocyst-gastrostomy is technically easier than
pseudocyst-jejunostomy, while remaining equally efficacious. Laparoscopic pseudocyst-gastrostomy
is technically easier, but cyst-jejunostomy is also technically feasible for the cyst not amenable to
gastric drainage by standard surgical principles.
Laparoscopic pseudocyst-gastrostomy was first performed by Petelin in 1991. Principles of operative
drainage include biopsy of cyst wall to rule out neoplasm, dependent drainage, and precise
hemostatic technique to avoid haemorrhage.
The patient position and port placement are the same as described for the bypass procedure. The
pseudocyst may often be seen pushing the stomach forward. A small gastrotomy is established with
cautery over the most prominent portion of the pseudocyst. Ultrasound may be helpful in locating the
pseudo cyst and the site of the initial gastrotomy. The gastrotomy is then extended for several
centimeters with electrocautery.
A small window is developed through the posterior wall of the stomach with electrocautery. One must
remember that the posterior wall of stomach and cyst capsule will be fused and that this requires a
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deeper dissection with cautery than may feel comfortable for the surgeon. Ultrasound may be helpful
in identifying the location of the pseudocyst, and in some cases to plan dissection where the stomach
wall or cyst is thinnest. The window is made large enough to accommodate the endoscopic stapler. A
biopsy of the wall may be carried out at this time. Two firings of the stapler are used to create a
substantial anastomosis (stapler insertion through the more comfortable 12-mm port, usually the
right). Hemostasis at the staple line should be assured. The gastrotomy is closed with either sutures
or staples.
CONCLUSIONS
The laparoscopic approach to pancreatic surgery has rapidly been shown to be of considerable value.
For splenectomy and adrenalectomy, it has become the procedure of choice for most elective surgery.
The laparoscopic approach to the pancreas has value with respect to staging, bypass procedures,
and pseudocyst drainage. Pancreatic resection is feasible, but must still be considered investigational.
http://www.laparoscopyhospital.com/laparoscopic_management_of_pancreas.htm
153
Oncogenes in Breast cancer
Dr. Ravi Kant, Manu Gupta, Vivek Gupta, Vishal Gupta, Ajay Yadav, Virendra,
Vinay Kamal, AK Mandal, Bina Ravi, BC Das
Direct DNA damage, aberrations in DNA methylation, mutation, or loss of expression of BRCA1/2 or
p53 genes, deregulated expression of c-Myc or cyclin D1 genes, and defects in DNA mismatch repair
genes may all cause defects in DNA damage-dependent cell-cycle checkpoint controls, contributing to
onset or progression, or both, of breast cancer.
In aggregate, it is estimated that 5% to 10% of breast cancer cases occur in families with significant
inherited risk. A general hypothesis in the field of hereditary cancer genetics is the "two-hit"
hypothesis, that a point mutation might be inherited in one allele of a candidate gene at a putative
susceptibility locus and that loss of heterozygosity (LOH) or another genetic alteration might occur in
the other allele of that locus later in life, leading to genomic instability and cancer. This model has
guided the identification of familial breast cancer genes.
Inherited mutations in TP53 are responsible for the Li-Fraumeni syndrome of hereditary breast
cancers, sarcomas, and other tumor types. More recently, mutations in the PTEN phosphatase (or
MMAC1) gene (on chromosome 10q22-23) were described in the Cowden syndrome of hereditary
breast cancers and multicutaneous lesions. In contrast to TP53, PTEN is not commonly mutated in
sporadic breast cancers. Other studies on rarer familial diseases have implicated mutations of the
STKII/LKBI gene (on chromosome 19 and involved in Wnt pathway signaling) in the Peutz-Jeghers
syndrome of hamartomatous polyps, breast cancers, gastrointestinal cancers, and reproductive
cancers and the MLH1 or MLH2, or both, mismatch repair gene(s) in the Muir-Torre syndrome of
gastrointestinal and genitourinary tumors and breast cancer. Finally, although initially proposed,
mutations in the ataxia-telangiectasia gene ATM (ataxia-telangiectasia mutated) do not appear to
contribute strongly to the risk of developing breast cancer.
Two important genes that confer risk for the far more pervasive, familial forms of breast cancer have
been identified: BRCA1 and BRCA2. Carriers of these mutant genes may display a range of cancer
risk, and the mutant genes are quite prevalent in certain populations. King and coworkers first
localized BRCA1 (breast cancer and ovarian cancer-1) to chromosome 17q21. The gene was
subsequently cloned and found to be novel, containing an amino-terminal, zinc- and DNA-binding
"ring finger" motif; a carboxyl-terminal BCRT "domain;" and a nuclear localization sequence.
Interestingly, mutations in this gene are particularly prevalent in breast cancers of Ashkenazi Jewish
women and other select populations. However, some families carrying BRCA mutations are nearly
devoid of multiple afflicted members. In other studies comparing different carrier populations, BRCA1
mutations have also been reported (but rarely) in women with no familial association of the disease.
These studies emphasize the variable penetrance of inherited risk conferred by this gene. Although
mutations in the BRCA1 gene are widely prevalent in patients with familial breast and ovarian cancer,
mutations are rarely detected in sporadic breast cancers. However, the BRCA1 protein is commonly
down-regulated in nonfamilial (sporadic) breast cancers due to methylation of the BRCA1 gene and
other mechanisms. Consistent with these findings are observations that antisense oligonucleotides
directed against the BRCA1 messenger RNA (mRNA) enhance the proliferation of breast tumor cells
and of mammary epithelial cells in culture in vitro. Correspondingly, other studies have demonstrated
that retroviral transfer of the nonmutated BRCA1 gene selectively inhibits the growth of non-BRCA1–
mutated breast cancer cells in vitro and in vivo in nude mice.
A separate gene, termed BRCA2 (on chromosome 13q13), is also associated with familial cancers of
the female and male breast and, to a lesser extent, the ovaries. This gene shares homology with
BRCA1, and its encoded protein has similar biochemical functions to BRCA1. However, as noted
above, although BRCA2 mutation confers risk of female breast cancer, its effects on risk of ovarian
cancer appear smaller than the risk conferred by BRCA1. Mutations of BRCA2 confer risk of male
breast cancer and (to a more limited extent) several other cancers, such as prostate cancer,
pancreatic cancer, non-Hodgkin's lymphoma, basal cell carcinoma, bladder carcinoma, and fallopian
tube tumors. Breast cancers of BRCA1/2 carriers have similar prognostic significance when matched
for other characteristics to the sporadic cases of breast cancer in noncarriers, although they more
often also show high nuclear grade, TP53 mutations, and amplification of the HER2/neu oncogene.
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Notably, as many as two-thirds of families with hereditary breast cancer appear to have non-
BRCA1/2 mechanisms of breast cancer initiation. Current studies, using CGH and cDNA microarray
analysis, suggest a distinct signature of chromosome gains and losses and gene expression for the
different classes of familial breast cancers (BRCA1, BRCA2, BRCAX) compared to sporadic breast
cancers
As noted earlier, the structure and function of the two distinct BRCA proteins appear to be similar.
Each appears to serve as an important regulator of cell-cycle checkpoint control mechanisms,
involving cell-cycle arrest, cell death (apoptosis), and DNA repair. BRCA1 appears to interact with the
p53 protein (leading to induction of the cell-cycle inhibitor p21) directly, with the RNA polymerase
holoenzyme, with the transcription factor CREB, with two proteins termed BAP1 and BARD1, with the
estrogen receptor- (ER- , suppressing its function), with the promoter of c-MYC (suppressing
expression of this protooncogene), and with promoters of other genes. BRCA1 and BRCA2 proteins
are also found in complexes with Rad51, a protein important for the cellular response to DNA
damage. In addition, BRCA1 is phosphorylated by the ATM kinase, in response to DNA damage.
Thus, the roles of both BRCA proteins are now emerging as central gatekeepers of genomic stability.
In studies of mice bearing a conditional knockout of the BRCA1 gene, its further functions have
emerged: mammary ductal morphogenesis and checkpoint control in the G1/S and G2/M phases of
the cell cycle. Perhaps most interesting among BRCA1 protein–protein interactions in mammary
epithelial cells is the one with the ER- . This apparently key antiestrogenic effect may place the
BRCA proteins on center stage for control of the sex steroid–regulated pathways, long suspected to
induce breast cancer.
Suppressor Genes and Oncogenes
The most common genetic abnormalities in the progression of sporadic and familial breast cancers
(as in many other types of solid tumors) appear to be LOH at multiple loci in Familial Disease, an
LOH event uncovers the functional consequences of a mutation in an allele of a tumor suppressor
gene by removal of the dominant, normal allele. At the present time, in addition to LOH of the TP53
gene and the two BRCA loci noted earlier in Familial Disease, LOH on 13q, 9p, and 16q are known,
respectively, to involve specifically the tumor suppressor genes RB-1, CDKN2 (encoding the p16
protein), and CDH1 (encoding the E-cadherin protein). RB-1 and CDKN2 regulate the cell cycle,
whereas CDH1 regulates differentiation and tissue compartmentalization. Other suspected tumor
suppressor genes involved in the progression of breast cancer have been proposed to reside on 1p,
3p, 6q, 7q, 11p, 11q, 15q, 17q, and 22q. For example, a plasma membrane inner leaflet-associated
protein termed caveolin-1 (on 7p3.1) has been proposed to be a tumor suppressor gene in breast
cancer. It is notable that two types of DNA alterations can lead to suppressor gene inactivation on
one allele, before LOH of the other allele. For example, although point mutation may be more
common for TP53 and possibly Rb, gene methylation may be more common for CDKN2 and CDH-1.
Additional genes that are commonly methylated in breast cancer include the gene encoding 14-3-3
(HME1, a G2 M cell-cycle checkpoint control gene on chromosome 1p35), GSTPI (a carcinogen
detoxification gene on chromosome 11p13), RAR 2 (a retinoid receptor gene on chromosome 3p24),
TIMP-3 (a matrix metalloprotease inhibitor on chromosome 22q13.1), the receptor a for estrogen
(ER- , on 6q 25.1), and the receptor for PRA progesterone (on 11q13).
In some cases, genomic areas containing tumor suppressor genes are also susceptible to complete
loss or deletion of both alleles. Certain tumor suppressor gene candidates, such as the gene
encoding the p27KIP1 cell-cycle regulatory protein, exhibit the characteristic of haploid insufficiency,
whereby (in contrast to TP53, BRCA1, BRCA2, PTEN, CDKN2, and CDH1) a single normal copy of
the gene is not fully suppressive of cancer. For this type of suppressor gene, mutation, deletion, and
LOH are not common in breast cancer.
Another common type of cytogenetic alteration in breast cancer is gene amplification. The initial step
in gene amplification is thought to be the formation of extrachromosomal, self-replicating units termed
double-minute chromosomes. These genetic elements later become permanently incorporated into
chromosomal regions and are termed homogenous staining regions. An amplified genetic unit
(amplicon) is thought to be initially much larger than the actual size of the principal gene(s) of biologic
importance to tumorigenesis. Thus, silent or irrelevant genes may be detected coamplified with one
or more expressed genes on an amplicon. The principal, best-established amplified and functional
genes for tumorigenesis (also called dominant oncogenes) detected to date in breast cancer are the
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growth factor receptor HER2/neu (c-ERBB 2 ), the nuclear transcription factors c-MYC and AIB-1, and
the cell-cycle kinase regulator CCND1. In some cases, multiple genes may be coamplified; for
example, GRB-2 and topoisomerase II, coamplified with HER2/neu, may contribute to breast cancer
pathogenesis. DNA gains are common on at least 35 distinct loci in breast cancer, including 6q, 8p,
8q, 11q, 12q, 13q, and 20q, although the specific genes involved in driving the chromosome
amplification process are still under active investigation. BAC array CGH, coupled with gene
expression microarray, has been used to catalog the genes reproducibly, up-regulated in association
with their amplification. For example, a neural survival factor termed dermocydin (on 12q 3.1) has
been proposed as an oncogene in breast cancer.
Central questions in breast cancer research focus on mechanisms of desensitization of the disease to
antihormonal therapy and on design of strategies to maintain antihormonal responses in patients.
Mechanisms include altered ER- isoforms, coactivators (AIB-1), signaling partners (PI3K), and
aromatase expression. Tamoxifen resistance of breast cancer is associated with cellular
hypersensitization to the weak estrogenic effects of the drug, perhaps due to expression of receptor-
associated regulatory proteins, receptor mutation, alterations in downstream growth regulatory
pathways (MAPK, PI3K), or selection for variant ER- receptor isoforms. An exon 5–deleted variant
of the ER lacks the hormone-binding domain and displays constitutively active, hormone-independent
transactivational characteristics. This receptor isoform is elevated in tamoxifen-relapsing breast
cancer. Expression of an exon 4–deleted ER variant correlates with low histologic grade and high PR.
Expression of other variants bearing deletions in exons 2 and 4 or 3-7 are associated with high-grade
tumors with high ER content.
Acknowledgement: The above excerpt has liberal quotes from original article by Robert B. Dickson,
Richard G. Pestell, Marc E. Lippman in Devita‘s Cancer-Principles and Practice of Oncology, 7th
edition ( Lippincott) Chapter 33: Cancer of the Breast: Section 1: Molecular Biology of Breast Cancer.
156
Investigations in a patient with early carcinoma breast
Dr. Shaji Thomas
1. Ductal Carcinoma in situ (DCIS)
Usually found on screening mammography in the asymptomatic patient
Investigations –
 Mammography: size of lesion, diffuse microcalcifications, multicentric disease
 Mammographically guided Core biopsy / excision biopsy
 Histopathology – rule out invasion, negative margins of resection, receptor status
2. Lobular carcinoma in situ (LCIS)
Discovered as an incidental pathologic finding on biopsy performed for another indication.

Absence of distinct clinical or mammographic findings.
Calcifications associated with LCIS typically occur in adjacent tissues - ‗neighbourhood
calcification‘ that is unique to LCIS and contributes to its diagnosis.
Investigations –
 If detected due to abnormal mammogram finding – core biopsy
 If core biopsy shows only LCIS, excision biopsy with mammographic needle localization
to avoid missing an invasive carcinoma or DCIS.
3. Early invasive breast cancer
 Mammography – should be ideally done before needle biopsy to avoid distortion of

architecture
 FNAC / core biopsy
 Ultrasound breast – as adjunct to mammography when indicated
 Magnetic Resonance Imaging of breast – only when indicated
 Metastatic workup – very low pickup rate. However, low cost investigations like chest
Xray, LFT, ultrasound abdomen are usually done routinely in all patients. Metastatic
workup is indicated in all patients with involved nodes (clinically or on pathology
specimen)
 PET scan – not indicated in early lesions
 BRCA mutation testing – only when indicated.
 Histopathology – should include exact size of tumor, type and grade of malignancy,
receptor status, HER2/neu growth factor receptor overexpression, involvement of
resected margins by tumor, number of resected lymph nodes and number of involved
nodes.
a) Mammography
 Should ideally be done before FNAC / core biopsy to avoid distortion of breast
architecture / haematoma.
 Delivers four times the radiation of a conventional chest Xray
 No increased breast cancer risk associated with screening mammography
 False positive rate of 10% and false negative rate of 7%
 Specific features of a malignancy – solid mass with or without stellate features,
asymmetric thickening of breast tissues, and clustered microcalcifications. BIRADS
staging (Breast Imaging – Reporting and Data System)
 Less reliable in young patients with dense breasts
 Also used to guide interventional procedures, including needle localization and needle
biopsy
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b) FNAC / core biopsy
 In a clinically and mammographically suspicious mass, sensitivity and specificity of FNAC

approaches 100%.
 FNAC requires an experienced cytopathologist for accurate interpretation
 Histopathologic type and grade of malignancy, ER / PR receptor status, HER2/neu status
can also be reported on cytopathology by an experienced cytopathologist using a cell
block.
 False negative rate for core needle biopsy is very low. However, a tissue specimen that
does not show breast cancer cannot conclusively rule out malignancy as sampling
error can occur.
 Histologic type and grade of malignancy, receptor status and HER2/neu status can be
easily made out on core needle biopsy.
 Fewer ‗suspicious for malignancy‘ report with core-needle biopsy. However, more painful,
and leaves a parenchymal scar.
 Any patient scheduled for neoadjuvant chemotherapy should have the tumour pathology
type and grade, receptor and HER2/neu status documented either on FNAC or core
needle biopsy before starting chemotherapy, for in patients with complete response to
chemotherapy, there will be no tumour tissue in the surgical specimen.
c) Ultrasound breast
 Not indicated in all patients. Only as an adjunct to mammography when indicated.

 Important method of resolving equivocal mammography findings, defining cystic masses,
demonstrating the echogenic qualities of specific solid abnormalities.
 If the lesion is demonstrated to be a simple cyst, no further investigation is required. If
shown to be a solid well circumscribed mass, will require 6 monthly follow-up for at
least 2 years. If a complex cyst or a solid mass without a clearly demonstrated well
circumscribed border, a biopsy is indicated.
 Most commonly required in younger patients with dense breasts
 Does not reliably detect lesions that are 1 cm or less. Masses in fatty breasts difficult to
visualize. Cannot reliably detect microcalcification. Inferior to mammography to detect
early breast cancer.
 Also used to guide fine-needle aspiration biopsy, fore-needle biopsy, and needle
localization of breast lesions.
d) Magnetic resonance imaging of breast
 Not used in the routine workup of diagnosed early breast cancer.

 In suspected breast mass of uncertain nature after mammography and ultrasound.
 High sensitivity, low specificity. No limitation from breast density. No radiation. Better
characterization as benign or malignant.
 However, one study of MRI of contralateral breast in women with a known breast cancer
showed a contralateral breast cancer in 5.7% of these women.
 Indicated in screening breasts of high-risk women. Women with a strong family history of
breast cancer, or who carry known genetic mutations require screening at an early
age, but mammography is of limited use because of the increased breast density in
young women.
 Disadv – high cost, unreliable depiction of microcalcification, claustrophobia, not done
with pacemakers or aneurysm clips.
e) Metastatic workup
 very low pickup rate in patients with early breast cancer. Not cost effective.
 However, low cost investigations like chest Xray, LFT, ultrasound abdomen are usually
done routinely in all patients.
 Metastatic workup is indicated in all patients with involved nodes (clinically or on
pathology specimen)
158
f) PET scan
 Not indicated in patients with early breast cancer.

 Sensitive and specific for detection of primary breast cancer and secondaries. Better than
CT / MRI for node, bone and liver secondaries.
 Studies in early breast cancer showed a high specificity for metastatic axillary lymph
nodes. Patients with early breast cancer who show positive axillary nodes on PET
should go for an ALND without sentinel node biopsy. However, presently this is not a
recommended indication for a PET scan.
g) BRCA mutation testing
 A heredity risk of breast cancer is considered if a family includes two or more women who
developed ovarian or breast cancer before age 50 years.
 Breast and ovarian cancer in the same individual and male breast cancer at any age, also
suggest the possibility of hereditary breast and ovarian cancer.
 50% of the women with a BRCA mutation have inherited the mutation from their fathers.
Approximately 50% of children of carriers inherit the trait.
 First test the affected family member. If a mutation is identified, then the relatives are
tested.
 A women who carries the deleterious BRCA mutation has a breast cancer risk of upto
85%, as well a greatly increased risk of ovarian cancer.
h) Histopathology
 Should include exact size of tumor, type and grade of malignancy, receptor status,
HER2/neu growth factor receptor overexpression, involvement of resected margins
by tumor, number of resected lymph nodes and number of involved nodes.
159
Surgical Options in Early Breast Cancer
Dr Gaurav Agarwal
Early breast cancers (EBC) include patients with invasive breast cancers measuring less than 5 cm
with or without mobile axillary lymphadenopathy who are free of any systemic metastases (TNM
stages T0-2, N0-1, M0). These are patients where the primary breast and axillary disease is
considered ―operable‖ or resectable, and a significant proportion of such patients can be offered
―cure‖. Even though the relative proportions of EBC amongst all breast cancer patients managed in
India and other developing countries is much smaller than the developed countries, owing to the large
overall number of breast cancer patients, it is important to be aware of the contemporary options for
management of this potentially curable group of patients. Further, with improving awareness and
diagnosis, the absolute numbers as well as the relative proportion of EBC patients in most centres is
on the rise.
Attempt has been made to provide an account of the current surgical practice for clinically detected
EBC in this article, with information on the surgical procedures on breast and axilla performed for
diagnosis, staging, cure of EBC and reconstruction or rehabilitation. The intention is to provide
practically usable notes on common surgical procedures, leaving out the details of emerging and not
yet established procedures such as skin preserving mastectomy, and plastic & reconstructive
procedures which seem beyond the scope of this article. Also, numerous other surgical procedures
that are not yet established as standards of care, including ―minimally invasive breast & axillary
surgical procedures‖, non-surgical options such as ―radio-frequency ablation‖, and surgical
procedures performed as part of adjuvant treatment such as oopherectomy and brachy-therapy
catheters implantation have been left out.
Management of EBC:
EBC is diagnosed in the following three scenarios:
1. A breast lump self detected by the patient- this is the commonest scenario in India.
2. A screen detected breast lesion on mammographic screening in an asymptomatic patient: Such
breast lesions are impalpable in most cases. This is an uncommon scenario in India and other
developing countries, but perhaps the commonest scenario in some countries of the industrialized
world.
3. On work-up of a woman presenting with asymptomatic axillary lymphadenopathy with occult
primary site: this is a rare scenario.
Surgical procedures may be required while managing EBC for one of the four reasons:
A. Establishing Diagnosis
B. Staging of the axilla
C. Curative surgery
D. Rehabilitation and reconstruction
Often, more than one of the above intentions is fulfilled at one time with a well planned and
executed surgical procedure.
A. Diagnostic Surgical Options for EBC:
The diagnosis of malignancy in a patient with suspected EBC- either with palpable breast lump or an
impalpable breast lesion- is essentially established by fine needle aspiration cytology (FNAC) from the
breast and/or axillary lymph-nodal mass. Rarely, a need for surgical excision/ incisional biopsy arises
to establish the diagnosis. Such situation may arise in following scenarios:
1. Inconclusive cytological diagnosis, but a high clinical suspicion for malignancy: an excisional
biopsy for histological examination- frozen section or paraffin section may be required in such
scenarios. A core needle biopsy (such as Tru-cut biopsy) can be an alternative to the
operative biopsy.
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2. Impalpable breast lesion- where FNAC is difficult or inconclusive: an image guided
localization and excision is required in this scenario. A per-cutaneous image guided biopsy
(such as vacuum assisted automated breast biopsy- Mammotome R) can be an alternative to
the operative biopsy.
Even when an operative biopsy is needed, all attempts should be made to make surgical
management of such a patient a one-stage procedure, by use of frozen-section histology, and
performing a wide local excision of the breast lump if that can be performed without major cosmetic
derangement. The various possible outcomes of the biopsy and their implications need to be
discussed with the patient before-hand, and appropriate consent to be taken to carry out a curative
surgical procedure in case the biopsy is reported as malignant.
Principles of Surgical Breast Biopsy:
The guiding principle while performing a surgical breast biopsy should be- to consider any clinically
suspicious breast lump or lesion as an invasive breast cancer, and to perform the initial diagnostic
surgical procedure in a manner that a future definitive or curative procedure is not hampered by the
initial procedure. At the same time, cosmesis and patient comfort too need to be kept in mind while
performing the breast biopsy. A correct placement of the incision for breast biopsy is an important
step- incisions need to be kept as central as possible, so that a future mastectomy if needed would be
possible, incorporating the scar of initial surgical procedure in the skin ellipse removed at mastectomy,
without hampering tension free primary skin closure. The incisions in the upper half of breast are
usually placed in a circumferential, curvi-linear manner, while those in the lower half of breast are
usually radial ones. These provide best cosmesis with least distortion in contour of the breast.
Whenever possible, the whole breast lump or lesion should be removed in-toto along with a 1 cm
margin all around, marking the cavity margins with radio-opaque clips to assist a possible future
radiation boost to the tumor bed. The cavity is not approximated and the wound closed without
drainage after haemostasis is achieved. An intentional seroma would invariably form in such cavities,
and help minimize the distortion of the breast contour. The breast lump removed should be measured
and orientation sutures placed to assist the pathologist make out the correct margins, who should
provide a comprehensive diagnosis based on the model histology reporting on breast biopsy
specimen (Table 1). This way, in case the lump is found malignant, and all the margins are free of any
tumor infiltration, a patient with no contra-indications and desirous of breast conservation treatment
would not need any further surgical procedure or re-operation on the breast.
Image-guided Localization and biopsy of an impalpable breast lesion:
Women who undergo a screening mammography may be detected with breast lesions that may be
considered suspicious of malignancy- these are categorized as BI-RADS TM assessment categories
4 or 5 lesions. For an image-guided wire localization and excisional biopsy, a breast radiologist (or at
times a surgeon trained in this procedure) puts a hook or wire through the screen detected breast
lesion under mammographic guidance. Ultrasonographic guidance can be used in patients with
ultrasonographically detectable lesions, and is more popular amongst surgeons who perform breast
ultrasound themselves. A hook is more stable as compared to a wire, and it should preferably be put
through a fibro-glandular tissue rather than just through fatty breast parenchyma. The wire or hook is
placed in a manner that the tip lies just beyond the margin of breast lesion. Putting in more than one
wire or hook is often better. A perfect placement of the wire is confirmed by a mammogram in two
projections. The wire or hook is stabilized by applying a sterile dressing over it, ensuring not to
entangle the wire or hook in the patient‘s clothing or dressing. The patient is then transferred to the
operating room, to be operated under general or local anaesthesia. An incision is made as
appropriate for that part of breast, and a few millimetres away from the entry point of the wire. Sharp
scalpel dissection is performed as scissors can transect the wire and diathermy can cause thermal
injury and breakage of the wire. Using the wire and mammogram films as guides to the breast lesion,
tissue wide of the tip of wire is excised with the scalpel, orientation sutures to mark the margins put,
and sent for specimen radiograph to confirm that the whole of lesion as seen on mammogram has
been removed. A few radio-opaque clips are preferably put to mark the margins of the cavity and
assist a future radiation boost if needed. The wound is closed without drainage.
Alternatives to an image-guided wire localization and biopsy are- percutaneous vacuum assisted
automated (Mammotome) breast biopsy and Radio-guided occult lesion localization (ROLL).
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B. Surgical Procedures for Cure of EBC and staging of axilla:
All breast cancer patients should be treated using a protocol based multi-modality treatment plan. The
SGPGIMS Lucknow protocol for management of EBC is summarized in table: 2. The primary
modality for treating EBC is Surgery, augmented by adjuvant radiation therapy to improved loco-
regional control of the disease and systemic therapy in form of chemotherapy and hormone therapy
for improving systemic control and overall survival of the patients. Use of Trastazumab in adjuvant
setting has been found to improve survivals of patients with HER-2-neu positive tumours, though a
routine adjuvant use of this immuno-therapy is still debatable. Yet, the primary and most important
component of treatment of EBC patients remains a surgical procedure to take care of the Primary
breast tumor and the axillary lymph-nodal basin. After a cytological confirmation of the malignant
breast pathology, breast imaging with bilateral mammography or ultrasonography, and the minimum
metastatic work-up in form of chest x-ray, blood chemistry including liver functions test, abdominal
ultrasonography and symptoms directed skeletal scan or radiographs, patients are offered surgical
treatment for the breast cancer with a curative intent.
The two components of primary surgical treatment of the EBC- Management of the breast primary
and the axilla- almost always go hand in hand. With better understanding of the disease process,
recognition of fact that the survival of breast cancer patients does not depend on radicality of the
breast surgical procedure, and use of evidence based medicine tools to test appropriateness of lesser
radical surgical procedure in management of EBC, the world has seen a dramatic and progressive
conservatism in management of the breast primary as well as the axilla. While standard surgical
procedure for breast primary has changed from a radical mastectomy to a wide-local excision in
appropriate patients over past 4 decades or so, the management of axilla has seen a paradigm shift
from a routine complete axillary dissection in all patients to avoidance of axillary dissection by use of
sentinel lymph node biopsy (SLNB) in selected patients with clinically impalpable axillary lymph nodes
in whom the SLNB is reported non-metastatic on histology.
Evolution of breast cancer surgery:
Even though there are mentions of breast surgical procedures in the medieval texts, the modern day
breast cancer surgery took birth in around circa 1750 AD with the descriptions of Petit of the
technique of total mastectomy. Towards the end of 19th century, Halsted described and popularized
the ―Radical Mastectomy‖, which was the standard procedure for most part of early 20 th century. By
late 1950‘s thoughts about reducing the morbidity of radical mastectomy by preserving some of the
structures and muscles starting emerging, and Patey‘s modified radical mastectomy became the
standard of care. Almost simultaneously, an even more conservative concept of breast conservation
by a wide local excision and radiation treatment emerged, and the trials of BCT conducted separately
by Veronesi and Fischer in early 1980‘s established these as safe and adequate surgical procedures
in selected patients. By early 1990‘s BCT became a standard procedure offered to majority of EBC
patients.
Contemporary breast surgery options for EBC:
As stated earlier, surgical management of the breast primary and the axilla almost always go hand in
hand. The current day options for management of the primary breast tumour are:
Whole breast removal options:

1. Modified radical mastectomy (MRM)- with a routine axillary clearance in all
2. Total mastectomy and Sentinel lymph node biopsy, proceed to axillary clearance if
sentinel lymph node is reported metastatic on histology
Breast Conservation options:

1. Wide local excision and occasionally quadrantectomy with routine axillary clearance
2. Wide local excision or quadrantectomy with Sentinel lymph node biopsy, proceed to
axillary clearance if sentinel lymph node is reported metastatic on histology.
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Breast conservation therapy for EBC has two essential components in form of a breast
conservation surgical procedure and radiation therapy.
The choice between a mastectomy procedure and BCT rests on various factors, and all patients
desirous of, and who do not have any contra-indications for BCT and radiation therapy should be
offered breast conservation surgery. Sufficiently large and high quality data is now available from
various trials conducted in different parts of the world to document no detriment in terms of overall
survival by conserving the breast, in comparison to mastectomy, though rates of local recurrence
following breast conservation surgery and radio-therapy are higher. Yet, mastectomy continues to be
the commonest form of curative surgical procedure due to various reasons including low acceptability
on patients‘ part, and lack of adequate radio-therapy and pathology infrastructure, training and skills at
most centres in India and other developing countries.
Modified Radical Mastectomy:
Modified radical mastectomy (MRM) is a composite surgical procedure combining complete breast
removal along with axillary dissection. Whole of the breast along with all fibro-fatty and lymphatic
tissue of the axilla are removed, saving both the pectoral muscles, axillary artery and vein, brachial
plexus, thoraco-dorsal neuro-vascular pedicle and nerve to serratus anterior.
The contemporary indications for performing a complete breast removal in a patient with EBC are:
1. Patient with contra-indications for BCT, such as multi-centric disease, contra-indications to
radiation therapy- pregnancy, certain connective tissue disorders.
2. Patients not desirous of BCT
A significant number of EBC patients who are candidates for BCT still opt to undergo a mastectomy
all over the world. Besides, a large number of EBC patients who can be offered BCT are still managed
with complete breast removal due to lack of appropriate radiation, pathology or surgical infrastructure,
training and skills in numerous hospitals.
Surgical technique of MRM:
Complete removal of the breast parenchyma is undertaken by removal of nipple areola complex along
with an ellipse of the breast skin (usually a horizontally oriented ellipse, so as to leave a transverse
horizontal suture line). Skin flaps are raised using diathermy, scalpel or scissors dissection in the
plane between the sub-cutaneous fat (small fat lobules) and breast parenchymal fat (large fat
lobules). The extent of flaps raised is between clavicle superiorly to anterior abdominal wall inferiorly
and the posterior pectoral fold or sub-scapular fold laterally to para-sternal plane medially. Viability
and blood supply of skin and sub-cutaneous tissue are ensured while raising the skin flaps, and the
flaps are bevelled by leaving slightly thicker layer of sub-cutaneous tissue as one gets closer to the
chest wall. This step, along with ensuring a tension free suture line is vital for good wound healing and
avoidance of skin flaps necrosis. Once the flaps are raised until the musculature of the chest wall is
exposed, the whole breast is lifted off the chest wall from medial to lateral side by a combination of
diathermy dissection and blunt dissection in a plane just superficial to the pectoral fascia, also ligating
or coagulating the perforating vessels.
Once the whole breast is lifted off the chest wall, the axillary tail is dissected, and the breast remains
attached laterally to the axillary tissue alone. The clavi-pectoral fascia is then incised just lateral and
parallel to the pectoral fold, thus gaining entering into the axilla. The pectoral muscles are retracted
supero-medially and dissection taken forward to expose the axillary vein, but ensuring never to
completely denude it of all soft tissue- thus reducing probability of arm edema. All fibro-fatty and
lymphatic tissue along with the lymph nodes are dissected off, restricting the superior extent of
dissection to just inferior to the axillary vein laterally, and infero-lateral to the medial border of the
pectoralis minor muscle medially. The lateral extent of the axillary dissection is restricted up to
anterior border of latissimus dorsi muscle. This procedure would routinely result in complete
dissection of levels 1 and 2 of axilla. The level 3 of axilla (medial to medial border of pectoralis minor)
is indicated in patients with enlarged level 3 lymph nodes or those with numerous and bulky level 2
lymph nodes. Some surgeons follow a policy of routine dissection of levels 1-3 axilla, which is likely to
be associated with slightly higher incidence of post-operative and delayed arm lymphedema. An
adequate axillary dissection is a vital step in management of patients with metastatic axillary lymph
163
nodes, and a minimum of ten axillary lymph nodes need to be made available to the pathologist for
evaluation. The pathologist should be able to provide information on the primary tumor, and the
resection margins, as per the model histology guidelines (Table 1). In patients with metastatic axillary
nodes, the number of axillary nodes harbouring metastases, and any extra-nodal spread are vital
information that determines the need for adjuvant irradiation to the chest wall, axilla and supra-
clavicular fossa. Of course, in patients with a non-metastatic SLNB, the entire axilla is considered free
of any metastases.
While performing MRM, both the pectoral muscles, axillary artery and vein, brachial plexus, thoraco-
dorsal neuro-vascular pedicle and nerve to serratus anterior are preserved. The inter-costo-brachial
nerves are preserved by some, with a possible benefit of reduced or no post-operative parasthesiae
on the medial aspect of arm. Once the axillary dissection is completed, the breast and axillary tissue
are removed as one, and hemostasis achieved. The wound is closed after putting in two suction
drains- one underneath the inferior breast skin flap, and the other in the axilla. The surgical wound is
closed transversely, preferably using sub-cuticular sutures, though interrupted skin sutures or skin
staples too are commonly used. The flap drain is removed in early post-operative period once the
effluent is no longer bloody, while the axillary drain is kept functional longer, until the effluent volume
comes down to less than 20 ml per day. Patients are advised to undertake active exercises of the
involved side shoulder starting first post-operative day to prevent movement restriction and other
morbidity.
The possible early post-mastectomy problems include skin flap necrosis which may need excision and
re-suturing, prolonged axillary drainage, seroma formation following removal of drains and
parasthesiae on medial aspect of arm.
Other options with a complete mastectomy include a simple mastectomy and SLNB in patients who
do not have palpable axillary lymph nodes (and enlarged lymph nodes detected on ultrasonography).
The SLN is removed using a combination technique (of blue dye and radio-pharmaceutical guided
detection of SLN) or blue dye alone technique through a small incision in the axilla directly over the
SLN as detected by a hand held gamma probe or through a small incision along the lateral and
superior part of elliptical skin incision for mastectomy. In case the frozen section histology of the SLN
is reported metastatic, a complete level 1 and 2 lymph node dissection is carried out.
The other option with mastectomy procedure is an immediate post-mastectomy reconstruction, though
the acceptance rates for the reconstructive procedures vary widely, and are in general low amongst
Indian women. A possible option of delayed post-mastectomy reconstruction (following completion of
adjuvant chemotherapy and radiation therapy) should also be discussed with the patient, and the
results of immediate and delayed post mastectomy reconstruction are more or less comparable.
Breast Conservation Surgery for EBC:
In patients who have no contra-indications for BCT (vide supra), and are desirous of the same, a
breast conservation surgical procedure can be undertaken. The predominant procedure performed in
such patients is a wide local excision (WLE), and the other option of quadrantectomy is practiced by
only a few surgeons and centres. The WLE procedure is carried out along with either a SLNB
procedure or an axillary dissection which are usually performed via a separate incision than the
incision for the WLE.
Surgical technique of WLE:
The incision for a WLE procedure is placed directly over the tumor. For tumours located in the upper
half of the breast, a curvi-linear circumferential incision is more appropriate, while for the lower half
breast tumours, a linear radial incision is preferable. After incising the skin and sub-cutaneous tissue,
flaps are raised beyond the lateral extent of the tumor on all sides, while the surgeon dissects- usually
with electro-cautery- in a plane 1 cm wide of the palpable tumor margins all around. The dictum is to
attempt a ―NO SEE‖ dissection- i.e. at no time during the procedure, the tumor margin should be
totally denuded and seen to the surgeon, thus ensuring that the tumor is removed with a wide margin
all around. Once the tumor is dissected all around, the surgical specimen is marked with orientation
sutures to help the pathologist provide information about the margins, and sent for frozen section
histology. In case the pathologist is able to see any infiltrated margin(s), a re-excision of that margin is
164
carried out, until the margin is reported free of tumor infiltration on frozen section histology. Many
centres do not rely on the frozen section histology for the purpose of evaluation margins, and in case
one or more margins are found infiltrated on paraffin section histology, the patient is re-operated in a
few days time to take care of the infiltrated margin(s). At times, a mastectomy may have to be
resorted to in case the margins are infiltrated, and further wider excision would leave a cosmetically
unacceptable breast. Another option in such situation is a mini-latissimus dorsi flap to fill in the cavity
and repair a large contour defect. At the end of the WLE procedure, the margins of the residual cavity
are marked using radio-opaque surgical clips to assist planning of radiation therapy boost to the tumor
bed. Hemostasis is achieved and the wound is closed without drainage, anticipating an intentional
seroma which helps avoid major contour defect in the area.
A post-operative irradiation to the breast with or without boost to the tumor bed is a must, following a
breast conservation surgery. Radical irradiation to whole breast is the norm, though accelerated
partial breast irradiation is the newer option, which is expected to result in better cosmesis. Radiation
boost to the tumor bed can be delivered either with interstitial implants to deliver high-dose rate
brachy-therapy or using electron or photon beam external radiation.
Options for management of the axilla in a patient undergoing breast conservation therapy include a
SLNB if patient does not have palpable axillary lymphadenopathy, or an axillary lymph node
dissection. The axillary dissection is usually performed through a separate 3 cm incision in the axilla,
and the rest of surgical steps are similar to those described above for axillary dissection as part of
MRM.
Sentinel lymph node biopsy:
SLNB is an important new concept that has resulted in a major change in management of EBC in
recent decade or so. It has changed the surgical approach by potentially reducing the number of
patients who require axillary lymph node dissection. In experienced surgical hands and with proper
pathologic work-up, the finding of a negative sentinel node (with sensitivity and specificity being >
90%) may safely avoid an axillary lymph node dissection. Controversy remains about the routine use
of SNB and the degree of surgical expertise required to safely and effectively employ this procedure.
Technique of SLNB:
A patient with N0 axilla is explained the procedure and consent is obtained to subject her to a SLNB
followed by a possible axillary dissection in case SLNB is reported metastatic. Specific information
need to be provided about a possible re-operation for axillary dissection in case the frozen section
histology of SLNB fails to detect metastases which are later detected on paraffin section histology.
The SLNB procedure can be performed using a colour (blue) dye, radio-pharmaceutical (99mTc-
sulfure/ antimony/ gold colloid) or a combination of blue dye and radio-pharmaceutical, which is the
preferred method, with highest sentinel lymph node detection rate and lowest false negative rates. At
SGPGIMS, Lucknow, the SLNB team comprised of the Breast surgeons, Nuclear Medicine physicians
and Pathologist follow a SLNB protocol of using combination of 1% w/v methylene blue dye and
99mTc-Antimony colloid, which are both produced in-house in the hospital, thus containing their costs.
40 MBq 99mTc-Antimony colloid is injected sub-areolarly about 12-24 hours prior to surgery. Lymph-
scintigraphy is performed in anterior and lateral projections. Later, 1-2 ml sterile methylene blue sub-
areolar injection is administered few minutes before skin incision.
Using a hand held gamma probe (Neo-probe 2000, Ethicon), the ―hot‖ SLN is sought in the axilla
trans-dermally, and marked on the skin. A 1-2 cm upper axillary skin crease incision is placed
posterior to the pectoral fold, or immediately on top of the marked SLN, and the incision deepened
using sharp scissors dissection. Blue lymphatics are looked for, and if found are traced supero-
medially into a blue coloured SLN. The hand held gamma probe draped in a sterile glove is used to
trace the areas/ SLN with radio-tracer concentration (hot area), and the dissection is continued with its
help. Once the SLN is identified, gamma-counts are taken in-vivo, and the sentinel lymph node
removed intact. Ex-vivo gamma counts are also taken on the SLN, followed by examination of the
axilla with gamma probe. In case any further ―hot‖ areas are found, attempts are made to locate and
remove further SLN‘s, and usually 1-2 nodes are expected to be identified in most patients. After all
hot and/or blue lymph nodes are removed, and the background counts in axilla are satisfactorily low,
the axilla is palpated with a finger through the SLNB incision to seek any enlarged lymph nodes,
165
which too are removed. All such lymph nodes removed are sent to the pathologists in vials containing
cold saline, marked as SLN‘s for frozen section histology and/or imprint cytology. In case the frozen
section histology detects metastatic disease in one or more of SLN‘s- a complete (levels 1-2) axillary
dissection is performed, extending the SLNB incision to 3-4 cms.
Each centre is expected to undertake a validation study of the various techniques involved in practice
of SLNB- the SLNB identification and removal by surgeons with help from nuclear medicine
physicians, and the pathological evaluation of the SLN. A validation SLNB study means carrying out
the SLNB followed by a complete axillary dissection irrespective of the histology of the SLN in a pre-
determined number of patients, to compare the SLNB histology vs. histology of all removed axillary
lymph nodes at axillary dissection to evaluate if the SLN histology is truly reflective of the histological
status of the whole axilla. Documenting acceptable SLN identification rates (>90%) and the false
negative rates (<5%) at such a validation study before embarking on a therapeutic SLN program and
offering it as a routine to patients is vitally important. At SGPGIMS Lucknow, in a validation study
conducted on 100 EBC patients, a SLN identification rate of 96% and false negative rate of <3% could
be achieved, thus giving the team the confidence and conviction to offer this procedure to EBC
patients as a routine without putting them at a high risk for residual disease and possible axillary
recurrence.
C. Reconstructive and Rehabilitative Surgical Procedures:
Following either a mastectomy or breast conservation surgery which might have left a cosmetic
defect, a wide variety of surgical options are available to improve the cosmetic outcomes.
These options for post-mastectomy reconstruction can be broadly divided into following categories:
1. Autologous tissue procedures: pedicle or free flaps- Commonest types of flaps used are
a. Pedicle transverse rectus abdominis myo-cutaneous (TRAM) flap
b. Latissimus dorsi flap
c. Free TRAM flaps are usually performed by plastic and reconstructive surgeons
trained in micro-vascular tissue transfer techniques.
2. Prosthetic reconstructive procedures- implants: silicone, saline filled, combination
Any of these procedures can be performed either as

1. Immediate/primary reconstruction (at time of primary breast cancer surgery), or
2. Delayed reconstruction (following completion of adjuvant treatment, or at any time later)
Patient where post-mastectomy irradiation is needed, pedicle flaps are preferred. Free flap is avoided,
or else delayed until completion of radiation therapy in such patients, as radiation may result in
disruption/ blockade of the micro-vascular anastomoses.
As the experience with breast conservation surgery is growing, BCT is increasingly being offered to
patients with large but operable breast cancers, or those where the breast- to tumor ratio is not
favourable for good cosmetic outcomes of BCT. In many of such patients, the post-WLE breast defect
can be taken care by filling in the cavity using a pedicle latissimus dorsi flap with good results.
Selected references:
For further details and reading the following sources of information or literature may be perused.
Management of Early Breast Cancer:

 http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf
 Singletary SE. Multidisciplinary frontiers in breast cancer management: a surgeon's perspective. Cancer. 2007
Mar 15;109(6):1019-29.
 Mirshahidi HR, Abraham J. Managing early breast cancer: prognostic features guide choice of therapy. Postgrad
Med. 2004 Oct;116(4):23-6, 32-4.
 Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E, Godwin J, Gray R, Hicks C, James S, MacKinnon
E, McGale P, McHugh T, Peto R, Taylor C, Wang Y; Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and
15-year survival: an overview of the randomised trials. Lancet. 2005 Dec 17;366(9503):2087-106.
 Burak WE Jr, Agnese DM, Povoski SP. Advances in the surgical management of early stage invasive breast
cancer. Curr Probl Surg. 2004 Nov;41(11):882-935.
166
 Cady B. The changing role of the surgical oncologist. Surg Clin North Am. 2000 Apr;80(2):459-69.
 Baum M, Houghton J. Contribution of randomised controlled trials to understanding and management of early
breast cancer. BMJ. 1999 Aug 28;319(7209):568-71.
 Winchester DP, Cox JD. Standards for diagnosis and management of invasive breast carcinoma. American
College of Radiology. American College of Surgeons. College of American Pathologists. Society of Surgical
Oncology. CA Cancer J Clin. 1998 Mar-Apr;48(2):83-107.
 Silverstein MJ. Recent advances. Diagnosis and treatment of early breast cancer. BMJ. 1997 Jun
14;314(7096):1736-9.
Mastectomy/ Breast Conservation Surgery or treatment:

 Fisher B, Anderson S, Bryant J, Margolese RG, et al. Twenty-Year Follow-up of a Randomized Trial Comparing
Total Mastectomy, Lumpectomy, and Lumpectomy plus Irradiation for the Treatment of Invasive Breast Cancer.
New England Journal of Medicine, 2002; 347(16):1233-1241.
 Rainsbury RM. Skin-sparing mastectomy. Br J Surg. 2006 Mar;93(3):276-81.
 Hughes KS, Papa MZ, Whitney T, McLellan R. Prophylactic mastectomy and inherited predisposition to breast
carcinoma. Cancer. 1999 Dec 1;86(11 Suppl):2502-16.
 Dowlatshahi K, Francescatti DS, Bloom KJ, Jewell WR, Schwartzberg BS, Singletary SE, Robinson D. Image-
guided surgery of small breast cancers. Am J Surg. 2001 Oct;182(4):419-25.
 Kuerer HM, Arthur DW, Haffty BG. Repeat breast-conserving surgery for in-breast local breast carcinoma
recurrence: the potential role of partial breast irradiation. Cancer. 2004 Jun 1;100(11):2269-80.
 Kuerer HM, Julian TB, Strom EA, Lyerly HK, Giuliano AE, Mamounas EP, Vicini FA. Accelerated partial breast
irradiation after conservative surgery for breast cancer. Ann Surg. 2004 Mar;239(3):338-51.
 Newman LA, Washington TA. New trends in breast conservation therapy.
 Surg Clin North Am. 2003 Aug;83(4):841-83.
 Apantaku LM. Breast-conserving surgery for breast cancer. Am Fam Physician. 2002 Dec 15;66(12):2271-8.
 Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation
therapy. Am J Surg. 2002 Nov;184(5):383-93.
 Macmillan RD, Purushotham AD, George WD. Local recurrence after breast-conserving surgery for breast cancer.
Br J Surg. 1996 Feb;83(2):149-55.
 Dershaw DD. Evaluation of the breast undergoing lumpectomy and radiation therapy. Radiol Clin North Am. 1995
Nov;33(6):1147-60.
Management of Axilla/ Sentinel Lymph Nodes Studies:

 Jatoi I. Management of the axilla in primary breast cancer. Surg Clin North Am. 1999 Oct;79(5):1061-73.
 Pain SJ, Purushotham AD. Lymphoedema following surgery for breast cancer. Br J Surg. 2000 Sep;87(9):1128-41.
 Pressman PI. Surgical treatment and lymphedema. Cancer. 1998 Dec 15;83(12 Suppl American):2782-7.
 Newman EA, Newman LA. Lymphatic mapping techniques and sentinel lymph node biopsy in breast cancer. Surg
Clin North Am. 2007 Apr;87(2):353-64, viii.
 Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in early-stage breast
carcinoma: a metaanalysis. Cancer. 2006 Jan 1;106(1):4-16.
 Kuehn T, Bembenek A, Decker T, Munz DL, Sautter-Bihl ML, Untch M, Wallwiener D; Consensus Committee of the
German Society of Senology. A concept for the clinical implementation of sentinel lymph node biopsy in patients
with breast carcinoma with special regard to quality assurance. Cancer. 2005 Feb 1;103(3):451-61.
 Kelley MC, Hansen N, McMasters KM. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Am J
Surg. 2004 Jul;188(1):49-61.
 Wilke LG, Giuliano A. Sentinel lymph node biopsy in patients with early-stage breast cancer: status of the
National Clinical Trials. Surg Clin North Am. 2003 Aug;83(4):901-10.
 Alazraki NP, Styblo T, Grant SF, Cohen C, Larsen T, Waldrop S, Aarsvold JN. Sentinel node staging of early breast
cancer using lymphoscintigraphy and the intraoperative gamma detecting probe. Radiol Clin North Am. 2001
Sep;39(5):947-56, viii.
 Hsueh EC, Hansen N, Giuliano AE. Intraoperative lymphatic mapping and sentinel lymph node dissection in
breast cancer. CA Cancer J Clin. 2000 Sep-Oct;50(5):279-91.
Table 1: Model histopathology report of an early breast cancer surgical specimen: SGPGIMS
Lucknow protocol
Patient name Age/sex Central registration no.
Side - Left/Right Date of reporting
Type of specimen Breast specimen Wide local excision/Segmental excision/ Mastectomy
Axillary Specimen- Axillary clearance/Axillary sampling/Sentinel node(s)
Gross Histology No. of lesions/Size of lesion/Site of lesion
No. of nodes dissected/grossly significant nodes/Sentinel nodes
(no. of blue/hot/both blue and hot)
Microscopy Tumor histology /grade of tumor/ Lympho-vascular invasion /margin status of
specimen/
No. of nodes positive/extra-lymphatic spread/sentinel node status
Immunohistochemistry Hormonal receptors (ER/PR) and HER-2-neu status
167
Table 2: SGPGIMS Lucknow Treatment protocol for early breast cancer
Early breast cancer- T1/T2, N0/N1, M0 disease

Stage I, IIA, IIB (T2N1)
Stage I, IIA, IIB
Breast conserving surgery Modified Radical Mastectomy {Level

In consenting patients with no 1, 2 axillary clearance) with/ without
contraindications +/- validation reconstruction
sentinel node studies. +/- validation sentinel node studies
Histological confirmation of
negative margins ensured. If
margins found positive
(see model histology section)
Chest wall & Axillary irradiation

If > 4 nodes +ve or
Breast irradiation Extra capsular nodal disease or
T3/ T4 disease or +ve margins
Axillary irradiation
If > 4 nodes +ve
Extracapsular nodal
invasion
Adjuvant Chemotherapy *
If T =/<1cm, Node –ve,
no chemotherapy
Adjuvant Hormonal therapy

Only if ER/PR positive
Pre-menopausal : Tamoxifen x 5yrs
Post-menopausal: Aromatase
inhibitors/ Tamoxifen x 5yrs
168
Other modalities in the treatment of early breast cancer
Dr. Geeta Kadayaprath
There has been a paradigm shift in the locoregional treatment of breast cancer with the advent of
breast conservation surgery.1, 2 Halsted described radical mastectomy 100 years ago. 3 His theory
hinged on the idea that locoregional treatment in the form of surgery would be curative if the disease
has not metastasised . His assertion that cancer progressesed systematically from breast to nodes
and then distally was proved wrong when it was clearly understood that breast cancer is systemic at
inception. It was demonstrated that equivalent outcomes could be obtained with less morbid surgery,
despite increased local recurrence .4 This ushered in the era of systemic treatment in the form of
chemotherapy .This did impact mortality rate but downplayed the impact of locoregional control on
overall survival. For all the changes in breast cancer management, the goal of therapy remains what it
used to be a century ago – eradication of all malignant cells in breast and regional nodes at the
earliest. This seems more possible with better screening measures which enable one to pick up
lesions early. Breast conservation therapy is an established method of treating early breast cancer.
One must, however not forget, that for optimum breast conservation therapy, radiation is a must. In
our country, modified radical mastectomy continues to be offered to patients with early breast cancer
due to lack of radiation facilities. Nevertheless, sentinel lymph node biopsy has replaced axillary
lymph node dissection in select group of node negative patients and accelerated partial breast
irradiation is all set to do away with the arduous 5 week long radiotherapy schedule. With these
improvements in treatment, the management of breast cancer is slowly evolving towards minimally
invasive approaches.5, 6
MINIMALLY INVASIVE TECHNIQUES
SURGERY REMAINS THE STANDARD OF CARE FOR LOCAL TREATMENT OF BREAST

CANCER
Alternatives to open breast surgery-

1. Percutaneous tumour excision
2. Radiofrequency ablation(RFA)
3. Interstitial laser ablation
4. Focused ultrasound ablation (FUS)
5. Cryotherapy
These techniques offer complete tumour ablation with less psychological morbidity, better cosmetic
results and reduced inpatient care compared with traditional surgery.
Minimally Invasive Diagnostic Methods
The standard diagnostic procedure for non palpable lesions at one time was open surgical biopsy.
This involved localisation of the lesion with J- wire under ultrasound or mammographic guidance and
wide excision of tissue around the tip of the wire. After radiologic confirmation of the presence of the
lesion, pathologic diagnosis can be established. This procedure is extremely accurate. However 80-
90% of these lesions turn out to be benign and unnecessary surgery is resorted to. This is highly
avoidable now with more refined percutaneous techniques of biopsy. Large core needle biopsy may
be resorted to in non palpable lesions under mammographic (stereotactic) or ultrasound guidance. A
14-gauge needle and an automated biopsy gun are used for the procedure and for lesions containing
microcalcifications. Specimen radiography is essential for verifying adequacy of sampling.7, 8
Diagnostic accuracy of this method is high with miss rates of 1-7% and extremely rare false
positives.9, 10 However, disease may be underestimated, with high risk lesions eventually proving to be
invasive cancer in 40-50% cases. To counter this shortcoming, vacuum assisted breast biopsy can
reduce high risk and DCIS underestimate rates as well as miss rates compared with large core needle
biopsy.11, 12 Routine use of this technique is not cost effective.
Image guidance for biopsy in the form of ultrasound, mammogram and MRI can contribute
significantly to accurate biopsy because of their high sensitivity and negative predictive value. Despite
all its advantages, one must always be aware that percutaneous biopsy can completely remove the
169
lesion, thereby hindering further complete surgical excision. Clips may be left behind to assist in
localisation of the lesion.
MINIMALLY INVASIVE TREATMENT MODALITIES
While the entire surgical world moves towards more minimally invasive approaches, surgical
oncology has also been evolving in the same direction. Ablative techniques are already in use for the
treatment of liver metastases. Several investigators have proposed the use of these methods in the
treatment of early breast cancer and benign tumours of the breast. I will briefly discuss the various
techniques used so far.
Percutaneous Stereotactic Excision
This modality has been used in the treatment of both benign and malignant lesions. Stereotactic
biopsy systems including the Advanced Breast Biopsy Instrumentation (ABBI) systems and
Mammotome have been used for this purpose. These instruments have excellent sensitivity and
specificity for diagnosis. However, with excisions, it is almost impossible to assess the tumour
margins. This approach is to be applied with caution in a highly select group of patients (old age with
co-morbidities). Prospective control trials are required to establish the usefulness of this procedure.
Radiofrequency Ablation
Radiofrequency ablation (RFA) has a well established role in the treatment of liver metastases and is
currently being used in select group of patients with early breast cancer. Jeffrey et al evaluated the
feasibility of this technique for patients with breast cancer.13 RFA utilises heat to destroy the tumour. A
radiofrequency probe 15G with electrodes is inserted into the centre of the tumour under image
guidance and an alternating high frequency electric current (400-500 KHz) is administered. At least
five minutes are required to reach the target temperature (95 deg.C).This temperature is maintained
for 15 minutes. This leads to irreversible tumour destruction as tumour cells are more susceptible to
heat than normal cells. The RFA targeted tumour volume to be ablated can be increased by
increasing the size of the electrodes but RFA has been found to be more successful with tumours up
to 3cms. in size. Cellular destruction can be confirmed by percutaneous biopsies or open biopsies.
Ablated tissues show coagulative necrosis and protein denaturation.
Various pilot studies have been carried out to assess the efficacy of RFA. A study conducted at MD
Anderson Cancer Centre demonstrated tumour ablation in 87% patients with breast cancers smaller
than 2 cm.14, 15 Another study by Izzo et al showed complete ablation in 25 of 26 patients.16 Finally
Hayashi et al treated 22 women with T1 N0 breast cancer with RFA followed by surgery 1-2 weeks
later.17 Tumour ablation was complete in 19 of 22 patients but 5 patients had residual disease at a
distance from the ablation zone. Quite clearly, as of now, RFA cannot be proposed as an alternative
to open surgery.
Focused Ultrasound Ablation (FUS)
After localisation of small tumours, ultrasound can be focussed to rapidly generate a significant
increase in local temperature up to 90 degrees by converting acoustic energy into heat.18 This causes
cell damage and tumour death. Duration of FUS ablation is usually 10 minutes. FUS has also been
used under MRI guidance.19 Wu et al randomised 48 patients to mastectomy or FUS followed by
surgery after 2 weeks. Tumour ablation was complete with no significant side effects.20, 21
Laser Ablation
Laser energy is delivered to the tumour through a fibreoptic probe inserted under image guidance. Nd
YAG, semiconductor diode and Argon laser have been used for this purpose. Laser ablation consists
of delivering 2-2.5 W in 500 s to the tumour. A target temperature of 80- 100 deg.C is generated
during 15-20 minutes to obtain tumour ablation. The end result is a central cavity surrounded by a
pale zone of liponecrosis. Small tumours can be ablated with negative margins.22, 23
Cryotherapy
Cryotherapy was initially developed and used in the treatment of non-operable liver metastases from
colorectal cancer.24 Cryotherapy used freezing to achieve tumour destruction.25 An external generator
170
using argon or nitrogen freezing system and a helium heating system are used to produce energy with
the help of a probe. The probe is inserted into the tumour under image guidance. After positioning, an
iceball is created at the tip of the probe. This iceball destroys the tumour as well as 5-10mm of
surrounding breast tissue. Temperatures ranging from -185 to +70 deg. C are generated. Tumour
destruction is the result of cell damage during the freeze thaw cycle. Cryotherapy is approved for
treatment of fibroadenomas. 26 Recently Sabel et al suggested that cryotherapy is safe for invasive
lesions less than 1.5 cms. but not for lesions more than 1.5cms.27 This method needs further research
to reduce the incidence of peripheral viable tumour cells.
CONCLUSIONS
Surgery remains the standard local treatment for breast cancer.

None of the ablative techniques described here are used alone in current clinical practice.
These techniques may be used for local treatment after careful discussion in elderly patients with co-
morbidities.
Large prospective randomised studies are needed to confirm the value of these treatments compared
with traditional open surgery.
References
1. Veronesi U, Cascinelli N, Mariani L et al.Twenty years follow up of a randomised study comparing breast
conserving surgery with modified radical mastectomy for early breast cancer. N Engl J Med 2002; 347:1227-1232.
2. Fisher B, Anderson S, Bryant J et al.Twenty year follow up of a randomised trial comparing total mastectomy,
lumpectomy, and lumpectomy plus radiation for the treatment of invasive breast cancer. N Engl J Med 2002;
347:1233-1241.
3. Halsted WS. The results of operations for the cure of cancer of the breast performed at The John Hopkins
Hospital from June, 1889- January, 1894. John Hopkins Hospital Bulletin 4, 1111(1894).
4. Fisher B, Redmond C, Poisson R et al. Eight year results of a randomised clinical trial comparing total
mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989;
320(13):822-828.
5. Singletary SE. Minimally invasive techniques in breast cancer treatment. Semin Surg Oncol 2001; 20:246-250.
6. Simmons RM. Ablative techniques in the treatment of benign and malignant breast disease. J Am Coll Surg 2003;
197:334-338.
7. Fishman JE, Milikowski C, Ramsinghani R et al. US- guided core needle biopsy of the breast: How many
specimens are necessary? Radiology 2003; 226:779-782.
8. Koskela AK, Sudah M, Berg MH et al.Add on device for stereotactic core needle breast biopsy: How many biopsy
specimens are needed for a reliable diagnosis? Radiology 2005; 236:801-809.
9. Verkooijen HM, Peeters PH, Buskens MH et al. Diagnostic accuracy of large core needle biopsy for nonpalpable
breast disease: A meta analysis. Br J Cancer 2000; 82: 1017-1021.
10. Verkooijen HM.Diagnostic accuracy of stereotactic large core needle biopsy for non palpable breast disease:
Results of a multicenter prospective study with 95% surgical confirmation. Int J Cancer 2002; 99:853-859.
11. Hoorntje LE, Peeters PH, Mali WP et al. Vacuum assisted breast biopsy: A critical review. Eur J Cancer 2003;39:
1676-1683
12. Kettritz U, Rotter K, Schreer I et al. Low risk palpable breast masses removed using a vacuum assisted hand held
device. Am J surg 2003; 186:362-367.
13. Jeffrey SS, Birdwell RL, Ikeda DM et al. Radiofrequency ablation of breast cancer: First report of an emerging
technology. Arch Surg 1999; 134: 1064-1068
14. Mirza AN, Fomage BD, Sneige N et al. Radiofrequency ablation of solid tumours. Cancer J 2001; 7: 95-102
15. Singletary SE, Fomage BD, Sneige N et al. Radiofrequency ablation of early stage invasive breast tumours: An
overview. Cancer J 2002; 8: 177-180
16. Izzo F, Thomas R, Delrio P et al. Radiofrequency ablation in patients with primary breast carcinoma: A pilot study
in 26 patients. Cancer 2001;92:2036-2044
17. Hayashi AH, Silver SF, van der Westhuizen NG et al. Treatment of invasive breast carcinoma with ultrasound
guided radiofrequency ablation. Am J Surg 2003; 185: 429- 435
18. Chen L, Bouley D, Yuh H et al. Study of focused ultrasound tissue damage using MRI and histology. J Magn
Reson Imaging 1999; 10: 146-153.
19. McDannold, Hynynen K, Wolf D et al. MRI evaluation of thermal ablation of tumours with focused ultrasound. J
Magn Reson Imaging 1998; 8:91-100.
20. Huber PE, Jenne JW, Rastert R et al.A ne non invasive approach in breast cancer therapy using magnetic
resonance imaging- guided focused ultrasound surgery. Cancer Res 2001; 61: 8441-8447.
21. Wu F, Wang ZB, Cao YD et al. A randomised clinical trial of high intensity focused ultrasound ablation for the
treatment of patients with localised breast cancer. Br J cancer 2003; 89: 2227-2233.
22. Mumtaz H, Hall- Craggs MA, Wotherspoon A et al. Laser therapy for breast cancer. MR imaging and
histopathologic correlation. Radiology 1996; 200:651-658.
23. Harms SE. MR guided minimally invasive procedures. Magn Reson Imaging Clin N Am 2001; 9: 381-392,vii
24. Ruers TJ, Joosten J, Jager GJ et al. Long term results of treating hepatic colorectal metastases with cryosurgery.
Br J Surg 2001; 88: 844-849.
25. Whitworth PW, Rewcastle JC. Cryoablation and cryolocalisation in the management of breast disease. J Surg
Oncol 2005; 90: 1-9.
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26. Kaufman CS, Bachman B, Littrup PJ et al. Cryoablation treatment of benign breast lesions with 12- month follow
up. Am J Surg 2004; 188: 340-348
27. Sabel MS, Kaufman CS, Whitworth PW et al. Cryoablation of early stage breast cancer: Work in progress report of
a mult-iinstitutional trial. Ann Surg Oncol 2004; 11: 542-549.
172
Surgery for the early and advanced cases of hypernephroma
Dr. Atul Goswami
RCC accounts for 3% of all adult malignancies. The behavior is more aggressive than carcinoma of
prostate and bladder. The main route of metastasis is blood born, however, 10% patients have
venous route of metastasis and renal vein and IVC may be affected. Rarely the tumor thrombus
extends into right atrium. The Lymph nodal metastasis is associated with poor prognosis and is
generally associated with advanced stages.
Surgical removal of the tumor especially in the early stages results in cancer free 5 years survival
rates of more than 75%. With the advent of newer modalities like ultra sound and CT Scan and their
common use in abdominal problems many RCC are being detected incidentally. Since this tumor is
resistance to chemotherapy and radio therapy, surgery remains the main stay of treatment. Various
options have been studied for local, advanced and metastatic carcinoma.
Localized Renal Cell Carcinoma

The treatment of choice is Radical Nephrectomy and it includes:
1. Early ligation of renal artery and vein.
2. Removal of kidney outside Gerota`s fascia.
3. Removal of ipsilateral adrenal gland.
4. Regional lymphadenectomy from the crus of diaphragm to the aortic bifurcation.
The role of extensive lymphadenectomy is controversial and it adds to the morbidity and does not give
any survival benefit. However berry picking i.e. removal of Para renal, and para-aortic lymph nodes for
sampling has been advocated to exactly stage the tumor.
The surgical approach depends on:
1. Size of the tumor
2. Location of the tumor
3. Habitus of the patient.
Incision: The choice of incision is transperitoneal; however other incisions are useful in getting better
access
1. Transperitoneal (Midline or subcostal)
a. It allows abdominal exploration for metastatic disease.
b. Early access to renal vessels.
c. Minimal manipulation of the tumor.
1. Thoraco-abdominal Incision
Large upper polar tumor.
2. Extraperitoneal flank incision
a. Elderly patients where the kidney is mobile.
b. Patients of the poor surgical risk with small tumors.
LAPAROSCOPIC RADICAL NEPHRECTOMY
Laparoscopy due to its cosmetic value as well as early recovery is gaining popularity in treatment of
urological procedures as well. The actuarial 5 year disease free survival rates are 91% for stage I (T1-
T2) disease. The indications includes:-
 Small tumor (8cms or smaller)
 Localized RCC
 No local invasion
 No renal vein involvement
Nephron sparing surgery
When the aim is to preserve the renal functions to avoid making the patient anephric nephron
sparing surgery is carried out. The feasibility of this surgery has emerged due to:-
1. Advances in renal imaging.
173
2. Experience with reno-vascular surgery.
3. Improvisation in prevention of renal ischemic injury.
4. Growing number of incidentally discovered low stage RCC.
5. Good long term survival after these surgeries
Indications for Nephron sparing surgery
1. Patients with bilateral RCC.
2. RCC involving solitary functioning kidney.
3. RCC involving one kidney with potential threat to other kidney i.e.;renal artery stenosis,
HDN , ch-pyelonephritis; ureteral reflux , calculus disease or systemic diseases such as
diabetic and nephrosclerosis.
Preoperative evaluation for nephron sparing surgery
1. Tests to rule out local extension or metastatic disease.
2. Imaging delineating intrarenal arterial and collecting system. (Three Dimensional CT
Scan is a useful diagnostic modality)
Advantages of Nephron sparing surgery
1. Survival rates comparable to radical Nephrectomy. Many studies have reported a
cancer specific survival rate of 78% to 100%.
2. The risk of post operative LTR in operated kidney is 10%.
Nephron sparing surgery and Renal function impairment
1. The patients are at increased risk of long term renal functional impairment from
hyperfilteration injury.
2. The pts with loss of more than 50% of renal tissue were at increased risk of developing
proteinuria, focal segmental glomerulosclerosis.
3. 24 hour urinary protein measurement should be carried out in patients with solitary
remnant kidney.
4. Low proteins intake and use of ACE inhibitors can reduce the risk of nephropathy in the
remnant kidney.
Nephron sparing surgery with normal opposite kidney
It is an accepted treatment in patients who have a single, small (less than 4cm) RCC and a
contralateral normal kidney.
Renal Cryosurgery
Cryosurgery is emerging as a nephron sparing surgery. It includes rapid freezing, gradual thawing,
and a repetition of freeze –thaw cycles. The aim of cryoablation is to ablate as much of the tissue as
that could have been removed with conventional surgical excision techniques.
The Mechanism underlying tissue cryodestruction is
1. Immediate cellular damage due to rapid freezing.
2. Delayed micro circulatory failure during slow thaw rates.
The cryoprobes are inserted in the kidney and a rapid cooling is achieved to -20 degree C which
causes cryo distrucion of the tissue.
The Cryoprobes can be inserted percutaneously or via Laparoscopic port. The Cryoablation is
monitored ultrasonographically. High resolution ultrasonic probes are available for percutaneous as
well as Laparoscopic route.
Cryoablation has evolved recently due to:
1. Availability of the better cryoprobes that can be used in open, percutaneous as well as
laparoscopic surgery.
2. The new sophisticated ultrasonographic technology that review the real time progression
of the process of cryoablation.
3. These ultrasonic probes are available that can be used via laparoscopic ports to monitor
the cryoablation process.
174
Advanced Renal Cell Carcinoma
The incidence of IVC involvement in patient with RCC is 4-10%.
1. It should be suspected in the presence of
a. Lower extremity edema.
b. Varicocele even in lying position.
c. Dilated superficial abdominal veins.
d. Proteinuria.
e. Pulmonary Embolism.
f. Right atrial mass.
g. Non functioning of involved kidney.
Diagnosis
1. CT Scan
2. USG
3. Transesophagcal echocardiography
4. Transabdominal colour Doppler
5. MRI is the non-invasive and accurate modality for presence and distal extent of vena-
caval involvenment.
Renal arteriography and CAG
1. It is essential in patients with vena caval thrombus as 30-40% of these patients shows
arterialization of a tumor thrombus.
2. Embolisation of these thrombus helps in shrinkage and easy removal of these tumor intra-
operatively.
3. the coronary angiography is carried out before putting these patients on cardiac bypass.
Why to treat?
Complete removal of thrombus is only curative way to treat these patients in the absence of distal and
lymph nodal metastasis.
The 5 years survival rates are 47% to 69% after complete removal.
Prognostic Factors
These current studies indicates no significant difference in cancer free survival in patients with
supradiaphragmatic or subdiaphragmatic disease.
Locally Invasive Renal cell Carcinoma
The tumor has tendency to grow in the adjacent organs like.
1. Posterior abdominal wall , nerve roots and paraspinal muscles.
2. It can invade liver at times surgery is some times indicates however use of pre-
operative immunotherapy may redefine the surgical out come in these patients.
Local Recurrence after Radical Nephrectomy or Partial Nephrectomy
1. In the absence of Metastatic disease surgical removal is the only valid option.
2. Local recurrence after nephron sparing surgery is 1.4 to 10% whenever feasible resurgery
in the form of partial nephrectomy or nephrectomy should be carried out. Anephric
patients should be put on chronic dialysis and subsequent transplantation programme.
Metastatic Renal Cell Carcinoma
Palliative nephrectomy should be carried out in patients with
1. Sever hematuria
2. Sever pain
3. Paraneoplastic syndrome.
4. Compression of adjacent viscera
However percutaneous renal angio-infarction can achieve same palliative effect as surgery.
175
Other treatment modalities for renal cell carcinoma
Dr Kim Mammen
CRYOABLATION (CRA)
CRA was carried out by percutaneous route using a MRI-compatible, argon-gas based cryotherapy
device with 2-and 3-mm diameter tapered cryotherapy probes. Treatment was MRI-guided ultrafast
multiplane T2-weighted single-shot and T1-weighted gadolinium-DTPA-enhanced gradient-echo
sequence. Freezing (-150°C) was done in two freeze-thaw-cycles (10 min) using two single probes.
For adrenal ablation, ice-ball volume was extended at least 5 mm beyond the tumor margins.
Cryotherapy dehydrates and derives tumor cells from blood supply by rapid freezing. Important
technical aspects for efficacy of the method are a double freeze-thaw cycle with rapid freezing and
slow thawing. In contrast to laser or radiofrequency ablation techniques the freezing process can be
precisely monitored without any specific temperature-sensitive pulse sequence by MR-imaging. In
addition the extension of tissue destruction (of liver not kidney) does not increase after completion of
the ablation thus the target volume can be precisely defined. However, histological studies on porcine
kidneys demonstrated areas of only sub lethal injury at the edge of the cryolesion. Thus well-evolved
ice-balls have to be created in order to avoid incomplete tumor necrosis.
Renal cryoablation can be delivered using an open, laparoscopic, or percutaneous surgical approach.
Following renal mass biopsy, single or multiple cryoprobes of varying diameter are placed into a renal
lesion based on tumor size and shape. Cryoprobes can achieve tissue temperatures as low as –
160°C within a few minutes utilizing the Joule-Thompson effect with circulating high pressure argon
gas. Based on animal data, the cryoprobes are configured to develop an ice zone to freeze the renal
mass with a minimum temperature of –19.4°C or lower in order for complete homogenous renal tissue
necrosis. A double freeze-thaw cycle is favored based on previous data that showed consistently
larger areas of necrosis when compared to a single freeze-thaw cycle. Also, it is necessary to extend
the ice ball by a minimum of 3.1 mm beyond the edge of the tumor in order to achieve a target
temperature of less than –20°C to 40°C at the tumor margin. To ensure adequate kill temperatures at
the periphery of the mass, the ice ball is extended 0.5 cm beyond the tumor edge. As such, the
maximum diameter of the ice ball is at least 1 cm larger than the tumor diameter. Furthermore, the ice
ball created by the cryoprobes can be monitored in real-time by ultrasound, CT, or magnetic
resonance imaging (MRI) to ensure that the ice ball incorporates the intended area of treatment. The
resultant cryoinjury is based on the size of the cryoprobe, the total freezing time, and the number of
freeze-thaw cycles.
With recent advances in imaging and probe technology, renal cryotherapy for RCC has evolved as a
valid option for treatment of small renal masses in select patients. Available 5-year studies indicate
that renal cryoablation is a safe and effective method for nephron sparing treatment of small renal
cancers. However, longer-term oncologic data are required before renal cryoablation can be
considered as a primary treatment modality for patients with small renal masses.
RADIOFREQUENCY ABLATION (RFA)
RFA was performed by use of an RF-generator with 200 watts capacity. A 7F probe (extended probe
tip 40 mm) was placed percutaneously into the tumor in general anesthesia. RF energy was applied
according to the manufacturer's instructions, starting with 80 watts and subsequently increasing, until
the initial impedance of 40 ohms rose significantly and energy application was automatically stopped
(roll-off). Finally the puncture channel was coagulated with 30 watts while the probe was stepwise
retracted. Treatment was controlled by contrast-enhanced multislice CT-monitoring. A super selective
transcatheter embolization using platinum microcoils of tumor vessels was performed one day before
RFA. Follow-up investigations were routinely performed using MRI or CT scan.
Minimally-invasive, percutaneous needle ablations including injection of drugs, application of high-

intensity focused ultrasound (HIFU), intracavitary photon radiation, microwave thermotherapy and
laser or beamer induced coagulations are widely used in the management of liver malignancies.
Ablation of tumor tissue by cryotherapy or hyperthermal radiofrequency is relatively new techniques
176
for this purpose and the feasibility of thermal based techniques for tumor ablation in other organs has
already been demonstrated.
Radio-frequency (RF-) ablation is physically based on a radio frequent current (460 kHz) that passes
through the target tissue from an active electrode (probe) towards dispersive electrodes (grounding
pads). The energy leads to ion agitations with subsequent conversion of friction into heat which
causes coagulative necrosis. Different devices are available: active electrodes (single or clustered)
may internally be cooled in order to increase the heating capacity. Other systems, such as the device
in the present study, based on expandable probes with a various number of prongs that are released
in the target tissue and vary in diameter between 2-5 cm. Depending on the capacity of the RF-
generator, the needle design, the electrical conductivity and perfusion of the target organ, lesions of
up to 5 cm diameter can be induced with a single probe. Some reports demonstrated percutaneous
ablation of small renal tumors in situ as part of an open surgical procedure, during laparoscopy, or
percutaneously under ultrasound, CT or MRI-guidance. It is known that an additional
devascularization of the tumor mass by previous embolization supports a better distribution of heat
due to a reduced convection of energy. Thus, a 5 cm renal cell carcinoma was ablated in a single RF-
session after previous transcatheter embolization. However, hilar occlusion during RF ablation of a
kidney tumor led to no increased thermal necrosis.
Since open nephron-sparing surgery of small renal tumors is suggested to be equally effective as
nephrectomy with regard to long-term survival and local tumor recurrence rates, the feasibility of
minimal invasive needle ablation techniques has to be proven by controlled clinical studies. Tumor
ablation in the presence of distant metastasis of renal cell carcinoma using thermal energy was first
described by Uchida and co-workers. This strategy was abrogated because patients with
disseminated disease were usually suggested to be without possibility of cure. However, recent
survival data of patients after resection of metastatic tissue and of patients after
immunochemotherapy strongly support resection of the primary or cytoreduction of secondary tumor
sites in conjunction with systemic therapy. Especially minimal invasive techniques provide an
encouraging alternative to achieve local tumor destruction since perioperative complications are less
pronounced compared to open surgery. Consecutively, such techniques provide a better life quality
for the patient by a shorter in-house period, less pain and a faster recovery due to the minimal
operative trauma. In fact, the present report demonstrates that metastatic and primary tumors of renal
cell carcinoma could be sufficiently destructed within the treated zone and remained progression free
for a longer period of time. Moreover, treatment-related complications of were neglectible and
hospitalization short.
In conclusion, CRT and RFA are safe, feasible and effective methods to destroy even large local or
metastatic lesions of renal cell carcinoma. Especially RFA has the potential of sufficient percutaneous
tumor ablation due to its advantageous relationship between probe diameter and lesion size.
Application can easily be performed and guarantees a rapid learning curve. The decreased risk for
bleeding, the shorter duration of hospitalization and a faster recovery of the patient encourage
minimal invasive percutaneous thermal based therapies due to life-quality and economic aspects. In
our opinion, predominantly metastasized patients with low performance status and high risk surgical
preconditions are eligible for such minimal invasive interventions. However, the concept of destruction
of metastatic tissue in conjunction with an adjuvant or palliative immunotherapy warrants further
clinical investigations in general and a longer follow up is required to obtain data on the long run for
local tumor control. Finally, patients with impaired renal function or elderly with significant co-morbidity
may additionally profit from those techniques to achieve local tumor growth and renal protection.
MEDICAL TREATMENT
Medical therapies are generally offered for locally advanced or metastatic renal-cell carcinoma and
much of the clinical experience with this approach is in patients with the clear-cell type. Because
response rates are low, the need to identify new therapeutic agents is great.
CHEMOTHERAPY
Rates of response to chemotherapy alone are low (roughly 4 to 6 percent). Drug resistance may be
related to the expression of the multi-drug resistance transporter in proximal-tubule cells — the cells
from which clear-cell and papillary renal-cell carcinoma may originate. Chemotherapy may be more
177
efficacious for advanced non–clear-cell renal-cell carcinoma, particularly the collecting-duct type. A
phase 2 trial of carboplatin and paclitaxel for the collecting-duct form of the disease is under way.
CYTOKINE-BASED THERAPY
Interleukin-2 (IL-2) and interferon (IFN) remain the standard treatment in Metastatic RCC (MRCC).
However, the results of recent studies might change the way patient will be given these treatments.
Intravenous Bolus IL-2

Intravenous (IV) bolus IL-2 is the gold standard. This treatment, despite its toxicity, provides
some long-lasting complete remissions. However, no study has ever been able to
demonstrate that this treatment provides any benefit in terms of survival over subcutaneous
IL-2 or IFN. Based on these considerations, IL-2 should be reserved for patients with good PS
and probably for those in the good prognostic groups.
IL-2 and IFN

A recent study reported at the 2005 meeting of the American Society of Clinical Oncology
(ASCO) has studied the role of IL-2 and IFN in the intermediate prognostic group, as defined
by the French group. In this study, called the Percy Quattro study, patients were randomized
to medroxy-progesterone acetate, IL-2, IFN and a combination of both cytokines. This study
has failed to demonstrate any survival benefit of IL-2 or IFN in the patients who do not receive
these cytokines over those who do receive them. Thus, continuing to give those patients
cytokines has become questionable, and should be considered only on a case-by-case basis.
TARGETED AGENTS
Better understanding of the physiology of clear cell carcinoma has in the past years led to a new
generation of drugs aiming at targeting the vascular endothelial growth factor (VEGF)/hypoxia-
inducible transcription factor (HIF) pathway. Through the interaction with the VEGF pathway, these
drugs block angiogenesis and could induce tumor shrinkage and/or tumor necrosis, leading to delay in
tumor growth. The decrease in tumor vascularisation has been observed by different radiological
approaches, including Doppler ultrasound or dynamic computed tomography (CT) scans. Results
from studies with these new agents have been recently reported and offer new strategic options for
the patients with MRCC.
BAY 43-9006
BAY 43-9006 (Sorafenib) is a multitarget tyrosine kinase inhibitor that interacts with many receptors
on the VEGF pathway, mainly VEGF R2 and platelet derived growth factor (PDGF). This oral drug has
shown promising activity and good safety profile in MRCC in phase 1. Recently, Escudier et al. the
results of a large randomized study in patients who had failed a first line treatment. In this 903-patient
study, patients were randomized to sorafenib and placebo. Tumor shrinkage have been observed in a
large majority of patients and progression-free survival has been improved significantly from three to
six months (p<0.0001). Survival data from this study will be reported shortly, and this drug is currently
tested as first-line therapy against IFN. SU11248
SU11248 (Sutent)
SU11248 (Sutent) is another multitargeted tyrosine kinase inhibitor that has activity in MRCC. Motzer
et al. recently reported (ASCO 2005) results from two consecutive phase 2 trials including more than
160 patients with MRCC who had failed first-line cytokine-based therapy. In these studies, high
response rate were consistently observed around 40%, with an overall survival around 16 months.
The activity of this promising drug will have to be confirmed through a large phase 3 trial comparing
SU11248 with IFN in untreated patients.
AG013736
AG013736 is the third drug reported at ASCO 2005 – this one by Rini et al. – with an impressive
activity in 52 patients (46% response rate). As SU11248, this targeted agent is an oral drug with a
good safety profile. Activity of this drug has yet to be confirmed in larger randomized studies.
Bevacizumab
Bevacizumab (Avastin) is an antibody against VEGF. This drug significantly improves progression
free survival, and is currently tested in combination with IFN through two large randomized studies in
untreated MRCC. In combination with gefitinib (Tarceva), promising response rates have been
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reported. However, a recent randomized study has been reported as failing to show benefit over
bevacizumab alone. Thus, the role of this antibody in MRCC remains to be determined.
Temsirolimus
Temsirolimus (CCI 779) is a mammalian target of rapamycin (mTOR) inhibitor, acting directly on HIF
production, a driver for the VEGF pathway. Activity of this drug have been reported in 2004 by Atkins
et al. and has yet to be confirmed through a large phase 3 trial currently in process in MRCC patients
in the poor prognostic group.9
In conclusion, the treatment of MRCC will change a lot in the next coming years; cytokine-based
therapy is currently challenged by a new generation of drugs targeting the VEGF pathway. It can be
anticipated that the use of both IL-2 and IFN will be restricted to very selected patients. Results of
large randomized studies that will soon be reported will help to better determine how to use these
different agents in the future. A combination of these drugs together or a combination with cytokines
might be of interest and such ideas are currently under investigation. In addition, the activity of these
drugs in adjuvant settings will have to be evaluated.
STEM-CELL TRANSPLANTATION
Allogeneic stem-cell transplantation performed after the administration of a non–marrow ablative
regimen elicits a potent graft-versus-tumor effect and appears promising for treating clear-cell renal
cell carcinoma. Protocols developed at the National Institutes of Health have used myelosuppressive
pretreatment, followed by an infusion of donor CD34+ cells and T cells from an HLA-identical sibling.
A course of immunosuppressive agents, such as cyclosporine, is used to limit graft-versus host
disease and is rapidly tapered. Twenty of the first 45 patients with metastatic renal-cell carcinoma who
underwent stem-cell transplantation had a response (44 percent). However, results in some other
centers have been less promising. The responses have correlated well with the development of graft-
versus-host disease and with the conversion of T-cell chimerism to full donor origin. One goal is to
identify the tumor epitopes that are initiating the graft-versus-tumor response to improve treatment
specificity. The two drawbacks to stem cell transplantation have been severe graft-versus host
disease, which can be life-threatening, and the need for a haplotype-matched sibling donor. Prognosis
is also an important guide to patient selection, since responses take several months. The next
generation of strategies for stem-cell transplantation may include the use of tumor vaccines after
transplantation as well as the use of cytokine therapy to boost recipient or even donor immunity.
TUMOR VACCINES
Tumor vaccines represent a potential means of enhancing host immunity. A promising approach to
the treatment of advanced clear-cell renal carcinoma uses autologous or donor dendritic cells, which
initiate a primary immune response by presenting antigen in the context of costimulatory molecules.
Dendritic cells can be pulsed with tumor protein, DNA, or RNA; they can even be fused with tumor
cells to present tumor antigens in a context favorable for therapy. Such vaccines are generally well
tolerated, but they will require further optimization. Concomitant administration of cytokines may
improve the response to vaccines.
TARGET ANTIGENS
A goal of stem-cell or vaccine therapies is to characterize the tumor antigens involved in the immune
response. One potential target is the G250 renal cancer antigen, which has been identified as CA9.
The CA9 gene is a target of HIF and so is over expressed in VHL-related clear-cell renal carcinoma,
even in the earliest lesions of von Hippel–Lindau disease. Thus, in cases of renal-cell carcinoma, a
high proportion of CA9-positive cells may be associated with
a more favorable prognosis. As a transmembrane protein, CA9 may also be a therapeutically useful
tumor antigen. It will be important to identify additional target antigens.
THERAPIES TARGETING VEGF AND TGF-A PATHWAYS

Originally identified as regulated by VHL, VEGF and TGF-a are now promising therapeutic targets in
clear-cell renal carcinoma. The manner in which these molecules interact with the cancer epithelium
and surrounding vascular endothelium leads to tumor progression. A combination of therapies based
on rational targets such as these may therefore be a powerful approach to advanced renal cell
carcinoma.
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VEGF-Pathway Components as Molecular Targets
VEGF is over expressed throughout clear-cell renal cell carcinoma tissue and may be the most
important tumor angiogenic factor. A randomized phase 2 trial involving patients with metastatic renal-
cell carcinoma investigated the efficacy of bevacizumab, a humanized VEGF-neutralizing antibody.
This agent extended the interval before tumor progression to 4.8 months, as compared with 2.5
months for placebo. Bevacizumab therefore provided a key ―proof of principle‖ of the efficacy of anti-
angiogenic therapy and may offer additional benefit when given in combination with other drugs.
Inhibitors of VEGF receptor tyrosine kinase are being developed and tested. Indeed, the multitargeted
kinase inhibitors sunitinib and sorafenib have shown great promise in phase 2 and phase 3 trials, with
at least stabilization of disease in as many as 70 percent of patients with cytokine-refractory disease.
TGF-a–Pathway Components as Molecular Targets

TGF-a is a potent growth factor for epithelial cells that acts through the epidermal growth factor
receptor (EGFR), which is a receptor tyrosine kinase. TGF-a is over expressed in the epithelium in
clear cell renal carcinoma and is a VHL target. Over expression of TGF-a is an early event in the
pathogenesis of this disease. Furthermore, growth of renal cancer cells in culture is dependent on
TGF-a. Thus, the TGF-a pathway is a logical choice for therapeutic intervention. Antibodies against
EGFR are thought to bind EGFR and promote its down-regulation from the cell surface. A fully human
monoclonal antibody against human EGFR, called panitumumab (ABX-EGF), has been evaluated in a
phase 2 trial involving 88 patients with metastatic renal-cell carcinoma. result. Small-molecule
inhibitors of the EGFR tyrosine kinase are also being developed. The quinazolines gefitinib and
erlotinib are now in phase 2 trials. Erlotinib is also being tested in combination with bevacizumab,
although encouraging initial results could not be confirmed in a randomized phase 2 trial.
OTHER APPROACHES
Temsirolimus (CCI-779), a selective inhibitor of efficacy in a phase 2 trial of metastatic renal-cell
carcinoma. Temsirolimus may inhibit HIF as well. Partial responses were noted in 7 percent of
patients, and minor responses in 26 percent. The median survival rate was 15 months. The notable
activity of the drug in patients with poor prognostic features prompted a phase 3 trial. Other options
are being pursued, including agents targeting HIF.
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Management of nephroblastoma
Dr. Madhu Sudan Agrawal, Akash Agarwal
Nephroblastoma, commonly known as Wilms Tumor, is the fifth most common pediatric malignancy
and the most common renal tumor in children. Fifty years ago, with surgery alone the survival rate 2
years after nephrectomy was 20%. The introduction of adjuvant radiation raised the survival rate to
50% overall. Now, with multimodal therapy including combination chemotherapy, the overall survival
(OS) rate has risen to 90%.
The annual incidence in children less than 15 years is approximately 7 -10 cases per million, and it
accounts for 6-7% of all childhood cancers1. Approximately 500 new cases are diagnosed each year
in the United States, with 6% of cases involving both kidneys.
ETIOLOGY:
The tumor may arise in 3 clinical settings:
(1) Sporadic: Most cases are not part of a genetic malformation syndrome and have no
familial history;
(2) In association with genetic syndromes:
 Hemihypertrophy, congenital aniridia or trisomy 18 mutation
 Beckwith-Wiedemann syndrome (macroglossia, gigantism, and umbilical hernia)
 WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations, and mental
retardation)
 Denys-Drash syndrome (Wilms tumor, pseudohermaphroditism, and glomerulopathy)
(3) Familial: Wilms tumor arises with high frequency in certain families.
MOLECULAR GENETICS:
Based on the model developed originally for retinoblastoma, Knudsen and Strong proposed that
Wilms tumor results from 2 mutational events based on loss of function of tumor suppressor genes.
The first mutation, the inactivation of the first allele of the specific tumor suppressor gene, involves
prezygotic and postzygotic aspects. The second mutation is inactivation of the second allele of the
specific tumor suppressor gene. Further, clinical characteristics of Wilms tumor suggest that the
molecular genetic mechanism in the second type of mutation depends on more than one tumor
suppressor gene.
 The WT1 gene (at chromosome 11p13) is a tissue-specific gene for renal blastemal cells and
glomerular epithelium. It is a dominant oncogene; hence, a certain mutation in only 1 of the 2
alleles is enough to promote changes that may lead to the formation of Wilms tumor.
 The WT2 gene (at chromosome 11p15) remains to be isolated.
Several genetic factors have been identified as possible prognostic factors in individuals with Wilms
tumor. One such factor is loss of heterozygosity (LOH) at chromosomes 1p and 16q. Children with
LOH at 16q appear to be at greater risk of relapse and mortality than children without this genetic
change.
PATHOPHYSIOLOGY:
The pathophysiology of nephroblastoma is characterized by an abnormal proliferation of the

metanephric blastema cells, which are felt to be primitive embryologic cells of the kidney.
Although most patients with a histologic diagnosis of Wilms tumor fare well with current treatment,
approximately 10% of patients have histopathologic features that are associated with a poorer
prognosis, and, in some types, with a high incidence of relapse and death. Wilms tumor can be
separated into 2 prognostic groups on the basis of histopathology:
 Favorable histology: Histologically mimics development of a normal kidney consisting of 3

cell types: blastemal, epithelial (tubules), and stromal. Not all tumors are triphasic, and
biphasic and monophasic patterns may present diagnostic difficulties. There is no anaplasia
in the tumor.
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 Anaplastic histology: extreme cellular pleomorphism and atypia2. Anaplasia is characterized
by the presence of three abnormailities: nuclear enlargement to three or more times the
diameter of adjacent cells, hyperchromasia of enlarged nuclei and abnormal mitotic figures. It
may be focal or diffuse. Focal anaplasia does not confer a poor prognosis, while diffuse
anaplasia does. Anaplasia is associated with resistance to chemotherapy and may still be
detected after preoperative chemotherapy3,4,5.
CLINICAL PRESENTATION:
The mean age at diagnosis is 3.5 years with more than 80% of cases occurring in those younger than
5 years. The most common feature at presentation is an abdominal mass (>90%). Abdominal pain
occurs in 30-40% of cases. Other signs and symptoms include hypertension, fever (from tumor
necrosis), hematuria, and anemia.
Major congenital anomalies include genitourinary anomalies (5% of cases); ectopic, solitary,
horseshoe kidney; hypospadias and cryptorchidism; hemihypertrophy and organomegaly (2% of
cases); and aniridia (1% of cases). Children with these syndrome anomalies should be checked
periodically for Wilms tumor. Ultrasonography of the kidneys (once or twice per year) is a good
screening tool.
INVESTIGATIONS:
Besides routine blood investigations (complete blood count, renal function tests and basic metabolic
tests) - imaging studies like ultrasonography, chest x-ray and computed tomography scan of the chest
and abdomen are performed to differentiate nephroblastoma from adrenal tumor (neuroblastoma), to
gain information regarding status of opposite kidney, possible renal vein or inferior vena cava (IVC)
thrombus, liver metastases, lymph node status and status of chest with respect to metastases. Bone
scans and magnetic resonance imaging are infrequently used.
STAGING:
The stage is determined by the results of the imaging studies and both the surgical and pathologic
findings at nephrectomy. Thus, patients should be characterized by a statement of both stage as well
as histological criteria (for example, stage II, favorable histology or stage II, anaplastic
histology)6,7.The staging system employed by the National Wilms Tumor Study Group and incidence
by stage is outlined below5.
Stage I (43%)
In stage I Wilms tumor, all of the following criteria must be met:
 Tumor is limited to the kidney and is completely resected.
 The renal capsule is intact.
 The tumor is not ruptured or biopsied prior to removal.
 No involvement of renal sinus vessels.
 No evidence of the tumor at or beyond the margins of resection.
Stage II (23%)
In stage II Wilms tumor, the tumor is completely resected and there is no evidence of tumor at
or beyond the margins of resection. The tumor extends beyond the kidney as evidenced by
any one of the following criteria:
 There is regional extension of the tumor (i.e., penetration of the renal sinus capsule,
or extensive invasion of the soft tissue of the renal sinus).
 Blood vessels within the nephrectomy specimen outside the renal parenchyma,
including those of the renal sinus, contain tumor.
Stage III (23%)

In stage III Wilms tumor, there is residual nonhematogenous tumor present following surgery,
and confined to the abdomen. Any one of the following may occur:
 Lymph nodes within the abdomen or pelvis are involved by tumor.
 The tumor has penetrated through the peritoneal surface.
 Tumor implants are found on the peritoneal surface.
 Gross or microscopic tumor remains postoperatively (e.g., tumor cells are found at
the margin of surgical resection on microscopic examination).
182
 The tumor is not completely resectable because of local infiltration into vital
structures.
 Tumor spillage occurs either before or during surgery.
 The tumor was biopsied (using tru-cut biopsy, open biopsy, or fine needle aspiration)
before removal.
 The tumor is removed in more than one piece.
Stage IV (10%)
In stage IV Wilms tumor, hematogenous metastases (lung, liver, bone, brain, etc.), or lymph
node metastases outside the abdominopelvic region are present. (The presence of tumor
within the adrenal gland is not interpreted as metastasis and staging depends on all other
staging parameters present.)
Stage V (5%)
In stage V Wilms tumor, bilateral involvement by tumor is present at diagnosis. An attempt
should be made to stage each side according to the above criteria on the basis of the extent
of disease
Stage I-IV Anaplasia

Anaplastic histology accounts for about 10% of Wilms tumors. Children with anaplastic tumors
have a worse prognosis than children with favorable histology when compared stage to stage.
These tumors are more resistant to the chemotherapy traditionally used in children with Wilms
tumor (favorable histology) 5.
TREATMENT:
With the advent of chemotherapy for treatment of Wilms Tumor, three major cooperative group trials
have been conducted with the goals to decrease the intensity of therapy to prevent late sequelae of
treatment while maintaining overall survival. The International Society of Pediatric Oncology (SIOP)
trials used preoperative chemotherapy before surgery in an effort to reduce tumor stage, and risk of
intraoperative rupture or spillage. The United Kingdom Children‘s Cancer Study Group trials used
preoperative chemotherapy and biopsy with the objective to avoid giving chemotherapy for benign
lesions and other non-Wilms tumors. The National Wilms Tumor Study Group, which is now part of
the Children‘s Oncology Group, has established standard treatment for Wilms tumor which consists of
surgery followed by chemotherapy and, in some patients, radiation therapy7,8,9.
Surgical principles:
1. Radical nephrectomy and lymph node sampling via a transverse transabdominal incision is
the procedure of choice10.
2. The most important role for the surgeon is to ensure complete tumor removal without rupture
and perform an assessment of the extent of disease.
3. For patients with resectable tumors, preoperative biopsy should not be performed10.
4. Routine exploration of the contralateral kidney is not necessary if technically adequate
imaging studies do not suggest a bilateral process.
5. If the initial imaging studies are suggestive of regional and contralateral kidney involvement,
the contralateral kidney should be formally explored to rule out bilateral involvement. This
should be done prior to nephrectomy since the diagnosis of bilateral disease would
dramatically alter the approach11.
6. Partial nephrectomy remains controversial and is not recommended. Rarely, very small
tumors may be discovered by ultrasound screening, and these cases may be considered for
partial nephrectomy12.
7. Hilar, periaortic, iliac, and celiac lymph node sampling is mandatory10. Furthermore, any
suspicious node basin should be sampled.
8. Margins of resection, residual tumor, and any suspicious node basins should be marked with
titanium clips. Liver wedge resection or partial duodenal or colonic resections are acceptable
for complete en bloc excision.
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Principles of chemotherapy:
1. Newborns and all infants younger than 12 months require a reduction in chemotherapy doses
to 50% of those given to older children13. This reduction diminishes toxic effects reported in
children in this age group while maintaining an excellent overall outcome14.
2. Liver function tests in children with Wilms tumor should be monitored closely during the early
course of therapy based on hepatic toxic effects (veno-occlusive disease) reported in those
patients15,16.
3. Dactinomycin should not be administered during radiation therapy.
4. Children treated for Wilms tumor are at increased risk for developing second malignant
neoplasms. This risk depends on the intensity of their therapy, including the use of radiation
and doxorubicin, and on possible genetic factors17.
5. Tumor-specific loss of heterozygosity for combined 1p and 16q predicts recurrence of FH
Wilms tumor and may be used to select patients for more aggressive treatment18.
Treatment recommendations:
Stage I:
 Nephrectomy with lymph node sampling and 18 weeks of chemotherapy with vincristine and
pulse-intensive dactinomycin.
Regardless of histology, all stage I Wilms tumor patients have an excellent prognosis with the
same treatment19.
Stage II:
For favorable-histology tumors:
 Nephrectomy with lymph node sampling and 18 weeks of chemotherapy with vincristine
and pulse-intensive dactinomycin.
For focal anaplastic tumors:
 Nephrectomy with lymph node sampling, abdominal radiation, and 24 weeks of
chemotherapy with vincristine, doxorubicin, and pulse-intensive dactinomycin.
For diffuse anaplastic tumors:
chemotherapy with vincristine, doxorubicin, etoposide, cyclophosphamide, and mesna.
Stage III:
For favorable-histology tumors:
chemotherapy with vincristine, doxorubicin, and pulse-intensive dactinomycin.
For diffuse or focal anaplastic tumors:
chemotherapy with vincristine, doxorubicin, etoposide, cyclophosphamide, and mesna .
Stage IV:
For favorable-histology tumors and focal anaplastic tumors:
 Nephrectomy with lymph node sampling, abdominal radiation according to local stage of
renal tumor, bilateral pulmonary radiation for patients with chest x-ray evidence of
pulmonary metastases, and 24 weeks of chemotherapy with vincristine, doxorubicin, and
pulse-intensive dactinomycin.
For diffuse anaplastic tumors:
 Nephrectomy with lymph node sampling, abdominal radiation, whole-lung radiation for
patients with chest x-ray evidence of pulmonary metastases, and 24 weeks of
chemotherapy with vincristine, doxorubicin, etoposide, cyclophosphamide, and mesna.
Stage V:
The treatment of children with bilateral Wilms tumor must be individualized. The goals of
therapy are to eradicate all tumor and to preserve as much normal renal tissue as possible
with the hope of decreasing the risk of chronic renal failure among these children20,21. Initially,
patients should undergo bilateral renal biopsies followed by preoperative chemotherapy with
vincristine and dactinomycin if the renal tumors are of favorable histology and stage I and II.
Those with higher stage and favorable histology disease should receive doxorubicin,
vincristine, and dactinomycin, and those with anaplastic histology should receive
cyclophosphamide in addition to vincristine, doxorubicin, and etoposide.
184
Following 6 weeks of chemotherapy, the patient should be reassessed for surgical resection
in the form of bilateral partial nephrectomy or wedge excision22.Chemotherapy and/or
radiation therapy following surgery is dependent on the response to initial therapy, with more
aggressive therapy required for patients with inadequate response to initial therapy.23,24,25
Studies demonstrate no difference in survival for children who undergo initial bilateral biopsy
followed by chemotherapy and then surgical resection compared with patients who have initial
resection followed by chemotherapy.
Bilateral radical nephrectomy is generally avoided due to difficulty in maintaining an anephric
child. Renal transplantation in such cases needs to be delayed until 1 to 2 years have passed
without evidence of malignancy26.
Inoperable Tumors:
Patients who have tumors with caval extension above the hepatic veins or that are so
massive that their surgeons consider the risk of initial surgical removal too great should be
biopsied and treated with preoperative chemotherapy24,27 with vincristine and dactinomycin
with or without doxorubicin. If no reduction in tumor size has occurred after using 3 drugs,
then radiation therapy should be used28. Surgery is performed as soon as sufficient tumor
shrinkage has occurred, generally at week 6 of therapy. Patients are subsequently treated as
for stage III tumors, which includes postoperative radiation therapy29.
PROGNOSIS:
Stage I For favorable-histology tumors 4-year overall survival rate is 98%30.
For focal or diffuse anaplastic tumors the 4-year overall survival rate is 82.6%5.
Stage II For favorable-histology tumors 4-year overall survival rate is 96%30, 31.
For focal or diffuse anaplastic tumors the 4-year overall survival rate is 81.2%5.
Stage III For favorable-histology tumors 4-year overall survival rate is 95%30.
For focal or diffuse anaplastic tumors the 4-year overall survival rate is 58%31.
Stage IV For favorable-histology tumors 4-year overall survival rate is 90%30, 31.
For focal anaplastic tumors the 4-year overall survival rate is 71.6%5.
For diffuse anaplastic tumors the 4-year overall survival rate is 44%5.
Stage V The 4-year survival is 94% for those patients whose most advanced lesion is stage
I or stage II, and 76% for those whose most advanced lesion is stage III32.
References:
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Tumor Study Pathology Center. Hum Pathol 19 (10): 1199-209, 1988.
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International Society of Paediatric Oncology (SIOP) experience. Med Pediatr Oncol 32 (5): 317-23, 1999.
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National Wilms Tumor Study. J Clin Oncol 6 (1): 51-5, 1988.
15. Green DM, Norkool P, Breslow NE, et al.: Severe hepatic toxicity after treatment with vincristine and dactinomycin
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1525-30, 1990.
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16. Raine J, Bowman A, Wallendszus K, et al.: Hepatopathy-thrombocytopenia syndrome--a complication of
dactinomycin therapy for Wilms tumor: a report from the United Kingdom Childrens Cancer Study Group. J Clin
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17. Breslow NE, Takashima JR, Whitton JA, et al.: Second malignant neoplasms following treatment for Wilm's
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18. Grundy PE, Breslow NE, Li S, et al.: Loss of heterozygosity for chromosomes 1p and 16q is an adverse
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Clin Oncol 23 (29): 7312-21, 2005.
19. Green DM, Children's Oncology Group: Phase III Multimodality Therapy Based on Histology, Stage, Age, and
Tumor Size in Children With Wilms Tumor, Clear Cell Sarcoma of the Kidney, or Rhabdoid Tumors of the Kidney,
COG-Q9401, Clinical trial, Completed.
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Wilms Tumor Study. J Urol 146 (2 ( Pt 2)): 514-8, 1991.
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syndromes. Cancer Res 60 (15): 4030-2, 2000.
22. Fuchs J, Wünsch L, Flemming P, et al.: Nephron-sparing surgery in synchronous bilateral Wilms tumors. J
Pediatr Surg 34 (10): 1505-9, 1999.
23. Horwitz JR, Ritchey ML, Moksness J, et al.: Renal salvage procedures in patients with synchronous bilateral
Wilms tumors: a report from the National Wilms Tumor Study Group. J Pediatr Surg 31 (8): 1020-5, 1996.
24. Ritchey ML: The role of preoperative chemotherapy for Wilms tumor: the NWTSG perspective. National Wilms
Tumor Study Group. Semin Urol Oncol 17 (1): 21-7, 1999.
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tumor. An analysis of cases from the Third National Wilms Tumor Study. Cancer 68 (2): 385-94, 1991.
26. Kist-van Holthe JE, Ho PL, Stablein D, et al.: Outcome of renal transplantation for Wilms tumor and Denys-Drash
syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant 9 (3):
305-10, 2005.
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(6): 1303-15, 1995.
186
Management of cystic renal masses
Dr Sanjay Gupta
Increasing use of imaging modalities such as ultrasonography, CT and MRI have led to detection of
asymptomatic renal masses. Majority of such lesions can clearly be characterized as benign or
malignant on the basis of imaging features and managed appropriately. However, in some small
lesions and complex cysts, radiological diagnosis is uncertain and additional measures such as close
follow-up, FNAC or biopsy may be required. This article deals with management of cystic lesions of
kidney.
Classification of renal cysts

Cystic renal disease is a heterogeneous entity consisting of heritable, developmental, and acquired
disorders. During the last decade, considerable progress has been made in reaching a consensus for
standard terminologies and classifications of cystic renal disease among radiologists, pathologists,
nephrologists, and urologists. Listed below is an accepted system of classifying cystic renal lesions1.
I. Localized cystic disease

A. Simple renal cysts, solitary and multiple
B. Localized, segmental, and unilateral renal cysts
II. Polycystic kidney disease
A. Autosomal dominant polycystic kidney disease
1) Glomerulocystic disease of newborn
2) Classic polycystic disease of older children and adults
a. Dominant polycystic disease linked to chromosome 16
b. Dominant polycystic disease not linked to chromosome 16
B. Autosomal recessive polycystic kidney disease
1) Polycystic disease of newborns and infants
2) Polycystic disease of older children and adults
a. Medullary ductal ectasia
b. Congenital hepatic fibrosis
c. Caroli syndrome
III. Renal cysts in hereditary malformation syndromes
A. Tuberous sclerosis
B. von Hippel-Lindau disease
C. Zellweger cerebrohepatorenal syndrome
D. Jeune asphyxiating thoracic dysplasia
E. Oral-facial-digital syndrome
F. Brachyesomelia-renal syndrome
IV. Glomerulocystic kidney disease
A. Infantile-onset dominant polycystic kidney disease
B. Syndromal glomerular cystic disease
C. Nonsyndromal glomerular cysts
V. Acquired renal cystic disease
VI. Renal medullary cysts
A. Medullary sponge kidney
B. Hereditary tubulointerstitial nephritis
1) Familial juvenile nephronophthisis
2) Medullary cystic disease
3) Renal-retinal dysplasia complex
VII. Renal cystic dysplasia
A. Multicystic kidney
B. Cystic dysplasia associated with lower urinary tract obstruction
C. Diffuse cystic dysplasia, syndromal and nonsyndromal
VIII. Extraparenchal renal cysts
A. Parapelvic lymphangiectasia
B. Perinephric cyst
Evaluation of cystic renal lesion
The goal of the evaluation of a renal lesion is to establish the most likely diagnosis and to detect
malignancy before local morbidity and metastases occur2. A detailed history and clinical examination
187
(especially family history), radiological examination and pathological evaluation (including genetic
studies, if indicated) are carried out.
History and physical examination

Although the evaluation of renal lesions is primarily radiographic, the history and physical examination
are often helpful. A family history of renal cell carcinoma may suggest a genetic predilection. Several
hereditary and systemic conditions predispose to renal abnormalities. Simple renal cysts usually do
not produce signs or symptoms but occasionally pain, hematuria, a palpable mass, urinary
obstruction, hypertension, proteinuria, polycythemia or jaundice is noted. Renal cell carcinoma may
produce hematuria, flank pain and a flank mass, and may be associated with paraneoplastic
syndromes. A history of fever, chills or urinary tract infection may suggest an infected cyst or renal
abscess.
Radiographic evaluation
Ultrasonography
As it is a widely used modality, most of the incidental lesions are first detected on
ultrasonography. It can reliably diagnose simple renal cysts on the basis of increased through
transmission, anechoic internal component, imperceptible extra-renal wall and sharply defined
intra-renal wall. Only when these criteria are not met is further imaging indicated. Addition of
colour doppler increases the sensitivity of ultrasonography. Ultrasound is the recommended
cost effective examination follow-up examination for a suspicious cystic lesion (2).
Recent developments in ultrasonography include tissue harmonic imaging which reduces

unwanted background noise, thus eliminating low-level echoes within an otherwise simple
cystic lesion. In one study, accuracy for classifying cystic lesions increased from 64% to 84%
by using pulse inversion harmonic imaging. Another development in this technique is the use
of intravenous microbubble contrast agents combined with pulse inversion harmonic imaging.
This has been found useful in characterizing cystic renal lesions, although this technique is
not yet in widespread clinical use (3).
Sonography is particularly useful in guiding nephron-sparing interventions, once it has been
decided to treat a complex renal lesion. Similarly, sonography can be employed to direct
percutaneous therapies such as radiofrequency ablation and cryotherapy of complex renal
lesions.
Computed tomography
CT remains the main method of imaging and characterizing cystic renal lesions. The decision
about whether a renal lesion is neoplastic is based on its enhancement properties and its
morphologic features. Cystic renal lesions are best evaluated with triple phasic multi– detector
row CT (unenhanced, arterial phase, and nephrographic phase). A change of less than 10 HU
from pre- to postcontrast images is usually considered typical of a benign cyst. Conversely, a
change within the solid portion of a cystic renal lesion of more than 15 HU is almost always
indicative of a pathologic process although not always a malignancy, as cystic
angiomyolipomas, oncocytomas, and infections may enhance (3). Although multi–detector
row CT is ideal for multiplanar reformation and volume rendering of cystic renal masses, it is
still unclear whether image processing adds substantially to the diagnosis of cystic renal
lesions.
Magnetic resonance imaging

MR imaging can play a major role in the evaluation of cystic renal masses. In patients with
allergies to iodinated contrast media or in whom renal insufficiency prevents the
administration of iodinated contrast media, gadolinium-based contrast agents can be
employed to detect enhancement. MRI is more accurate in hyperdense renal cysts and for
evaluating venous involvement3. However, MRI has disadvantage that unlike CT, where
attenuation measurements are reproducible, the arbitrary signal intensity units of MR imaging
must be standardized for each examination.
Dimercaptosuccinic Acid (DMSA) Renal Scintigraphy
DMSA scintigrams, which differentiate parenchymal lobulations from space-occupying
lesions, largely have been replaced by CT. Evolving single photon emission tomography
(SPECT) techniques may enhance the usefulness of DMSA2.
188
Angiography
The angiographic findings of hypervascularity and hypovascularity, although suggestive of
renal cell carcinoma and renal cyst, respectively, are not conclusive. This fact and the
invasiveness of angiography have led to its general replacement by CT or MRI in most cases.
Excretory Urography (IVP)

With the advent of newer modalities, it has become apparent that the sensitivity of IVP for
small renal masses is limited (67% for renal cell carcinoma 3 cm. or less)2. Findings
suspicious for a mass effect in the kidney on IVP should prompt further radiographic
evaluation.
Positron emission tomography (PET)

Fluorine-18-2- fluoro-deoxy- D -glucose positron emission tomography (PET) has been used
to evaluate its efficacy in detecting renal tumours and characterizing indeterminate cysts. In a
study on 21 patients with known renal masses subjected to PET scan, there were no false-
positive PET interpretations (confirmed by subsequent surgery, cytology or follow-up), and the
authors concluded that a negative PET scan and negative cyst aspiration helped in
diagnosing a benign lesion4.
Percutaneous aspiration / biopsy

An exact tissue diagnosis of a lesion is desirable for instituting appropriate management. This
approach is well established in case of many organs such as liver and lung. However, in case
of renal lesions, this approach is still debated. There are three chief reasons for this.
Firstly, increasing refinement in imaging techniques has led to their higher sensitivity
and specificity. Majority of renal lesions can now be correctly diagnosed by a good
quality CT scan, ultrasonography and MRI. Today, the vast majority of masses that
are difficult to diagnose by imaging are complicated cystic lesions, pseudo-tumours
(including anomalies), tumours that are not treatable surgically (lymphoma or
metastatic disease from a distant primary lesion) and small lesions (<3 cm)5.
Secondly, the reported sensitivity and specificity varies in different series and
depends on whether FNAC or core biopsy is used, the imaging modality used for
guidance, the size and nature of lesion (solid or cystic), the experience of operator
and the exact technique used. In general, positive biopsies are more specific and can
be relied upon, while negative biopsies could be due to failure to obtain
representative tissue and indicate need for excision biopsy. In a novel study on in
vitro core biopsy of radical nephrectomy specimens, the sensitivity, specificity,
positive and negative predictive values and non-diagnostic specimen rates of the
procedure were found to be 90, 91, 98, 63 and 25 percent respectively6.
Thirdly, there is a real worry about the complications of bleeding, infection and spread
of tumour in the needle tract (especially urothelial malignancy).
Despite these reservations about the procedure, FNAC and core needle biopsy are
continually being evaluated. A recent development in this direction has been the use of
molecular biology techniques (eg flow cytometry) on the biopsy specimen, in addition to the
cytopathologic and histopathologic evaluation. Laparoscopy directed FNAC and core biopsy
has also been attempted to improve the results7. Table 1 lists the current indications for
biopsy of a renal lesion.
The Bosniak classification of renal cystic masses
The Bosniak renal cyst classification was first introduced in 1986 and has been accepted by urologists
and radiologists as a way of diagnosing, discussing, and determining the management approach to
cystic renal masses. Using the lesion‘s morphology and enhancement characteristics, each lesion can
be categorized into one of five groups (categories I, II, IIF, III, and IV; Table 2), with associated
recommendations for patient treatment. With additional experience during the past two decades, the
Bosniak renal cyst classification has been updated and refined. These modifications include
189
introduction of category IIF which need follow up and the realization that contrast enhancement, rather
than calcification, is suspicious of malignancy8.
Table 1- Suggested indications for FNA cytology of renal masses

Sr Indication Lesion Symptom/ condition
1 If there is clinical or Lymphoma  Splenomegaly
radiological evidence to  Distant extrarenal
suggest a lesion other than lymphadenopathy
RCC  B symptoms
Abscess  Flank pain
 Fever and leukocytosis
 Pyuria
Metastatic disease  Previous extrarenal neoplasm
 Multiple lesions
(unilateral/bilateral)
 Other secondaries (liver, lung,
bone, etc.)
2 To obtain a histological Disseminated
diagnosis if there is a disease
relative contraindication for Unresectable
nephrectomy tumour
Single functioning
kidney
Co-existing
morbidity
Relative indication
for FNA
Indeterminate
cystic renal lesion
± ex Bosniak
category IIF
(follow-up)
While this system of classification was developed using high quality CT scans, attempts have been
made to use it based on ultrasonography and MRI evaluation. Since enhancement is difficult to
comment on ultrasonography, its use for Bosniak classification is not recommended. MRI, on the
other hand, can show enhancement and is being evaluated at present. Presence of enhancement is
an indication for surgery.
Management of cystic renal masses
Bosniak category I & II
Although most of these cysts are asymptomatic and require no further attention, some are
associated with abdominal or flank pain, obstruction of the collecting system, hematuria,
infection, or hypertension. For patients with symptomatic, peripheral, simple cyst in whom
medical management with narcotic or non-narcotic analgesics has failed or has become
excessive, percutaneous or surgical intervention may be considered.
Percutaneous aspiration for cytology and sclerosis should be attempted as a diagnostic and
therapeutic first step in the evaluation and treatment of simple renal cysts. Percutaneous
puncture can ascertain if cyst decompression results in resolution of pain and can justify
further, more invasive treatment. The radiographic appearance, along with sampling of the
cyst fluid for cytology, also can establish the benign nature of the cyst with some measure of
certainty. Unfortunately, as a definitive procedure, simple percutaneous drainage is
associated with a high rate of fluid reaccumulation.
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TABLE 2 Bosniak renal cyst classification system
Category Description Management
I  A benign simple cyst Cysts in this category do not
 Hairline thin wall that does not contain require further evaluation
septa, calcifications, solid components
 Measures water density
 Does not enhance
II  A benign cyst Cysts in this category do not
 May contain a few hairline thin septa in require further evaluation
which ―perceived‖ enhancement may be
present
 Fine calcification or a short segment of
slightly thickened calcification may be
present in the wall or septa
 Uniformly high attenuation lesions < 3 cm
(so-called high-density cysts) that are well
marginated and do not enhance are
included
IIF (F for  Cysts that may contain multiple hairline thin These lesions require follow-
follow-up) septa or minimal smooth thickening of their up studies to prove
wall or septa benignity.
 Perceived enhancement of their septa or
wall may be present
 Wall or septa may contain calcification that
may be thick and nodular, but no
measurable contrast enhancement is
present
 Lesions are generally well marginated
 Totally intrarenal nonenhancing high-
attenuation renal lesions > 3 cm are also
included
III  ―Indeterminate‖ cystic masses that have These are surgical lesions.
thickened irregular or smooth walls or Some will prove to be
septa in which measurable enhancement is benign (eg, hemorrhagic
present cysts, chronic infected cysts,
and multiloculated cystic
nephroma).
Others will be malignant,
such as cystic renal cell
carcinoma and
multiloculated cystic renal
cell carcinoma
IV  Can have all the criteria of category III These are clearly malignant
 Also contain enhancing soft-tissue cystic masses.
components adjacent to, but independent These lesions include cystic
of, the wall or septum carcinomas and require
surgical removal
The percutaneous instillation of sclerosing agents into simple renal cysts is associated with a
lower rate of recurrence than simple aspiration. A variety of substances have been used as
sclerosing agents with varying success, including alcohol, tetracycline, minocycline, lipidol,
iophendylate, povidone-iodine, and bismuth phosphate. Success rates of this procedure
range from 75% to 97% with complication rates ranging from 1.3% to 20%. With the high
success rate and low morbidity, percutaneous management should comprise first-line therapy
in most symptomatic benign simple cysts9.
191
Peripelvic cysts comprise a unique subgroup of benign simple cysts for which the anatomic
proximity to the renal hilum and collecting system render percutaneous puncture potentially
dangerous. Sclerotherapy is contraindicated because of the risk for injury from extravasation
of the sclerosing agent or entry into the collecting system.
For cysts that fail or are unsuitable for percutaneous sclerotherapy, endoscopic management
offers an alternative treatment modality. Isolated reports of endoscopic cyst marsupialization
from a retrograde ureterorenoscopic or a percutaneous approach have been published.
Percutaneous resection of benign renal cysts also has been reported in which complete
resolution without recurrence rate of 56% was achieved.
Traditionally, when cysts fail percutaneous or endoscopic maneuvers, open surgical cyst
decortication is indicated. A prohibitively high 32% perioperative complication rate has
discouraged open surgery in all but severely symptomatic patients.
Transperitoneal laparoscopic unroofing of benign renal cysts has been reported from 1992
onwards. This new technique offers a safe, effective, and less morbid alternative to open cyst
decortication. The cyst is exposed laparoscopically, the extrarenal cyst wall is excised and
any suspicious lesions in the cyst are sampled (similar to an open surgical procedure). The
inner surface of the cyst is fulgurated and/or a pedicle of perirenal or omental fat is placed into
the base of the cyst. Complete visual evaluation of all surfaces of the cyst is an advantage of
laparoscopic resection. This technique can be applied to all but completely intrarenal cysts.
Laparoscopic cyst resection also has been performed in patients with polycystic kidney
disease with most patients experiencing dramatic improvement in pain, stabilization of renal
function, and improvement in blood pressure.
Bosniak category IIF
As mentioned earlier, these cysts show non-enhancing areas of thickening and include cystic
lesions that are slightly more complex than category II, but not complex enough to fulfil the
criteria for category III. These lesions are thought to be benign, but require follow- up
computed tomography (CT) examinations to show their stability over time and thus prove their
benignity. This follow-up approach has been shown to be safe and has prevented an
unnecessary surgical intervention in more than 95% patients8.
Placing a lesion into a specific category can be difficult in some cases, especially
differentiating between category IIF and III. In such a case, placing the lesion into the higher
category with surgical intervention is appropriate, particularly when partial nephrectomy is
possible. However, if one is uncertain about differentiating category II from category IIF
lesions, follow-up studies should be the approach (category IIF), and not surgery (or biopsy).
Bosniak category III
These are truly indeterminate masses and need surgery. Some of these may turn out to be
benign after excision. The aim is to minimize the incidence of surgery for benign lesions by
using meticulous radiology technique. Role of FNAC / needle biopsy is debatable, as
discussed earlier.
The treatment of choice in these patients is radical partial or total nephrectomy. Since some
of these lesions will ultimately prove to be benign, partial nephrectomy is preferred, whenever
possible. While open surgery is an option, an increasing number of these procedures are
being carried out by laparoscopic approach.
There are reports of laparoscopic cyst exploration followed by directed FNAC and biopsy.
Patients who were diagnosed as having malignancy subsequently underwent appropriate
radical surgery. No worsening of prognosis was reported in these patients10. While attractive,
this approach needs further evaluation.
192
Bosniak category IV
These lesions are malignant and treated by total or partial radical nephrectomy. Procedure
can be performed laparoscopically, though open surgery remains the gold standard.
Limitation of Bosniak classification
The Bosniak renal cyst classification is not a pathologic classification of cystic renal masses, as is
evident by the presence of benign and malignant lesions in category III. It suggests a patient
treatment scheme determined according to the imaging characteristics of a cystic renal mass. It does
not directly take into account the clinical factors of the case, including patient age, patient
comorbidities, clinical history (eg, infection, trauma, previous imaging studies), or mass location within
the kidney, that can affect management. For instance, a complex cystic mass that is believed to
represent a category IIF lesion in an elderly patient would require serial follow-up examinations to
demonstrate stability of the mass with time and therefore its benignity. However, if the same category
IIF mass was in a young healthy patient, this management scheme might not be as clearcut. Because
no data are available to suggest when it is safe to stop following up a category IIF lesion, it may be
appropriate to remove this lesion (8).
Alternative and adjunct techniques for renal surgery
Angioembolization
The most accepted indication is for relief of hematuria, flank pain and other local problems associated
with metastatic or unresectable disease. Angioembolization cannot be considered curative therapy for
localized renal cell carcinoma.
Intraoperative ultrasound
Several investigators have found intraoperative ultrasound to be helpful in characterizing renal
lesions2. Findings on intraoperative ultrasound may lead to alteration of the intraoperative approach in
some patients being considered for partial nepherectomy. During laparoscopic cyst resection for
polycystic kidney disease, a laparoscopic ultrasound probe is useful for identifying cysts that
otherwise might not be detected.
Role of new energy modalities
New energy sources for ablation (high intensity focused ultrasound, interstitial radiofrequency
coagulation, laser-therapy, cryotherapy and microwave coagulation) may eventually allow
replacement of tumor resection by open surgery with tumor destruction by minimally invasive means.
High intensity focused ultrasound and microwave coagulation have the potential for extracorporeal
application, while lasers, cryotherapy and interstitial radiofrequency coagulation require at least
percutaneous or laparoscopic access. The limitation of all of these alternative energy sources is that
of imaging. Without direct visual monitoring of the ablation process, there is less certainty about the
completeness of treatment. Ultrasonography currently is the technique most readily applied to monitor
ablation by these energy sources.
References
1. EL-Merhi FM, Bae KT. Cystic renal disease. Magn Reson Imaging Clin N Am 2004; 12: 449–467.
2. Wolf JS Jr. Evaluation and management of solid and cystic renal masses. J Urol 1998; 159(4):1120-1133.
3. Hartman DS, Choyke PL, Hartman MS. A practical approach to the cystic renal mass. Radiographics 2004;
24:S101–S115.
4. Goldberg MA, Mayo-Smith WW, Papanicolaou N, Fischman AJ, Lee MJ. FDG PET characterisation of renal
masses: preliminary experiences. Clin Radiol 1997; 52: 510–5.
5. Bosniak MA. Problems in the radiologic diagnosis of renal parenchymal tumors. Urol Clin North Am
1993;20:217—30.
6. Dechet CB., Kletscher BA, Bostwick DG, King BF, Blute ML, Engen DE, et al. Prospective analysis of
computerized tomography and fine-needle biopsy of renal tumors. J Urol 1997; 157(2):326.
7. Limb J, Santiago L, Kaswick J, Bellman GC. Laparoscopic evaluation of indeterminate renal cysts: long term
follow-up. J Endourol 2002; 16:79–82.
8. Israel GM, Bosniak MA. An update of the Bosniak renal cyst classification system. Urology 2005; 66: 484–488.
9. Pearl MS, Traxer O, Cadeddu JA. Renal cystic disease. Urol Clin North Am 2000; 27(4):661-673.
10. Bellman GC, Yamaguchi R, Kaswick J. Laparoscopic evaluation of indeterminate renal cysts. Urology 1995;
45:1066-1070.
193
Disaster management
Dr. Gulshanjit Singh
Introduction
Triage in disaster situations
A disaster has been defined as a sudden massive disproportion between hostile elements of any kind
and the survival resources that are available to counterbalance these in the shortest period of time.
During such an emergency situation, shortages of personnel, equipment, and transportation vehicles
may necessitate triage carried out at various levels. Triage decisions must take into account these
variables. In war the priority is to return the soldier to action; after a civilian disaster such as a nuclear
accident, or large chemical spill, an earthquake or a train accident, it may be appropriate to use
limited resources for those most likely to survive. It may not be possible in such situations to render
the level of medical care to which people have become accustomed. Doing the greatest good for
greatest number of people using the available resources may influence the decision making process.
The situation may be chaotic and a system that is simple and clear is most likely to succeed. Triage
should be a tool by which a seemingly unmanageable, overwhelming situation can be organized.
Triage should be a dynamic process carried out at several levels throughout the system.
In the disaster situation where resources are limited, decisions made may have to be address the
greater good and some patients may receive only palliative care. Because few people have first hand
experience of conducting triage in a disaster situation and may find it distressing to restrict patients to
palliative care, an alternative has been suggested. The START, or simple triage and rapid transport
system, proposes five categories. Using a color coded system, it includes a blue category for patients
who are unlikely to survive or whose survival would depend on receiving extensive or complicated
treatment rapidly. Patients in this category would receive treatment after priority one but before
priority two cases, provided there numbers were not so large as to detract from the treatment of
urgent patients. Those conducting triage may find this a more acceptable method, but the addition of
a category may also lead to increased confusion. Whatever the method used in field, it should be
familiar to the hospital personnel at receiving facilities, and the principles of triage should be applied
to victims as they are treated in the definitive care setting. (1)
It is vital to weed out the patients who will do well with minimal care and those who will die despite
maximal care and then focus on those who will benefit the most from optimal trauma care and rapid
surgical intervention. (6)
Correct triage is crucial and has profound effect on the management of disaster victims. It may be the
most important medical task performed at the disaster site. Therefore it is reasonable to assume that
triage should be conducted by personnel with appropriate experience. In the incident command
system one member of the emergency medical crew to arrive at the scene will initiate the role of
triage officer until being relieved by a more senior person, if necessary. In military medicine and in the
civilian setting this role has been traditionally been adopted by an experienced surgeon.
The Advanced Trauma Life Support (ATLS) course has been suggested as a good framework for the
training of personnel in this disaster triage. ATLS involves a standardized approach that could be
adopted on an international level to aid communication between different teams at a site. (1)
Accumulated experience has led to use of a simplified triage algorithm in the Emergency Department
for arriving Mass Casualty Incident casualties. This algorithm is based on the degree of urgency of
necessary interventions rather than on the detailed severity of injury of the patient. Severely injured
patients are not necessarily the first to arrive and may continue arriving for an unknown period of
time. It is therefore prudent to reserve operative capacity for as long as possible. Immediate surgery
is provided for patients requiring life saving and/or limb saving intervention. With this approach, in an
overwhelming event, life saving surgical capacity will ultimately be limited only by the number of
expert surgical teams on location.
In the disaster situation, during an Mass Casualty Incident, the limit of hospital capacity to perform
optimal triage for all arrivals and provide quality care to select critically injured patients is easily
exceeded. The Emergency Department may be inundated with minor/moderate injuries impairing the
194
ability for a sufficient and timely response to the more urgent casualties. This issue was examined by
Hirshberg et al, who found that saturation may occur with a critical casualty load of 4.6 patients/hr
using immediately available resources and of 7.1 patients/hr during full deployment of all hospital
trauma assets. The delicate balance between over triage and under-triage is easily disrupted, initially
leading to either missed diagnoses with an increased critical mortality or a level of care that becomes
dependent on availability of resources outside the Emergency Department.
―Surgical Conservatism‖ (deliberate suspension of surgery for patients who were severely injured but
not yet in immediate danger of loosing life or limb) is being practiced during Mass Casualty Incidents
in different Level I trauma centers.
The majority of critically injured patients have abdominal, thoracic, or vascular injuries, creating an
immediate demand for the relevant surgical services and for anesthesiologists. Upon notification of an
event, elective surgery should immediately be suspended until the scale of the event is clarified.
Elective patients who are already in the Operating Room holding area either remain there until more
information becomes available regarding the scale of the Mass Casualty Incident or are sent back to
the ward. The elective patient who has already undergone anesthesia but not surgery should be
considered individually. Other urgent surgery cases should be included in the triage list with the Mass
Casualty Incident casualties.
Severely injured Mass Casualty Incident patients are often demanding even when their injuries are
not immediately life-threatening. In the Operating Room, a significant part of the experienced staff
may be engaged in treating one individual patient, particularly since multiple surgical procedures are
often performed in parallel during the first several hours. From the viewpoint of the Emergency
Department, once thus occupied in the Operating Room this staff will be unavailable to treat still
arriving patients. Withholding less urgent surgery also allows these trained teams to be put to good
use in the Emergency Department, improving the efficacy of patient triage, management, and
admission. (2)
There are four important factors which should be considered by a surgeon in trauma situation:
(1) Many patients even with severe injuries do not necessarily require surgery to survive for
many days or even weeks.
(2) Appropriate surgical skill and equipment are difficult to import and may not be usable under
difficult or dangerous circumstances.
(3) Inadequate surgery is worse than nothing.
(4) A basic level of nursing care could achieve much.
A surgical facility is expensive, requires enormous input of staff relative to the number who benefit
from it, and is a form of aid that must be delivered on an individual basis. The Medical Division of the
International Committee of Red Cross has learnt that when there is limited resources or difficulty of
access to a conflict zone, a surgical action alone might be inappropriate because many more lives are
saved by providing clean drinking water, food, and shelter or by merely protecting the population‘s
access to health services that would otherwise be denied. (4)
Who is a trauma surgeon?
The patient with multiple system injuries cannot tolerate fragmented care; the trauma surgeon must
be
(1) cognizant of diagnostic options and employ them at the right time in the right patient;
(2) able to prioritize and coordinate treatment of multiple injuries;
(3) capable of operating in the neck, chest, abdomen, and extremities to definitely manage
life threatening vascular as well as visceral wounds, and
(4) responsible for the critical care of their patients. Unfortunately the recent trend in surgical
practice and training render the qualified trauma surgeon increasingly scarce. (3)
Should surgeon be at emergency department?
Protocols to determine which trauma patients should be transported to trauma centers instead of
closer general hospitals are considered ‗primary triage.‘ Such systems are intentionally designed to
‗over triage‘ (i.e. to send more patients to trauma centers than necessary) in hopes of minimizing the
rates of ‗under triage‘ (i.e. sending patients who truly need trauma centers to general hospitals). The
American College of Surgeons has suggested that an over triage rate of 30% to 50% is ‗acceptable‘
195
and an under triage rate of 5% to 10% is ‗unavoidable‘. American College of Surgeons trauma center
certification requirements state that a general surgeon ―is expected to be in the emergency
department upon arrival of the seriously injured patient.‖ Advances in the speed and resolution of
computerized tomography during the past 2 decades have lead to a dramatic decrease in the need
for urgent laparotomy, however, and now substantially fewer injured patients receive emergency or
urgent operative intervention by a general surgeon. General surgeons describe a growing
dissatisfaction partly related to the increasingly non operative nature of trauma care and partly related
to the sacrifices required to maintain their immediate availability for trauma patients.
To decrease the burden on their surgeons, many trauma centers are increasingly using schemes of
so-called secondary triage (i.e., criteria based protocols whereby lower-risk patients arriving at trauma
centers can be evaluated by emergency physicians without the immediate, mandatory involvement of
a general surgeon) curiously, existing criteria for secondary triage have been formulated to predict the
same outcomes as primary triage (i.e., mortality and global injury severity).
For adults, summoning a surgeon for any one of the 3 high- yield criteria (penetrating mechanism,
systolic blood pressure < 96 mm Hg, pulse rate > 104 beats/min) could reduce surgeon‘s call by
51.2% of cases while failing to identify emergency operative intervention in only 0.08% of cases. For
children, no rule at all (i.e., never automatically summoning a surgeon) would fail to identify
emergency operative intervention in only 0.35% of cases, and use of a single high-yield criterion
(penetrating mechanism) would reduce surgeon‘s call by 96.2% while failing to identify emergency
operative intervention in only 0.09% of cases. Given the blood pressure and pulse rate thresholds
selected by CART for adults are not easy to remember, we repeated these analyses using rounded
numbers with similar rule performance. (5)
Can we provide quality trauma care?

Many trauma care providers view disaster preparedness as a field in which they are obliged to take
part but that they do not find very stimulating. This is because a multiple casualty incident (MCI) is
perceived primarily as a logistic and organizational problem rather than a trauma care problem. The
prevalent view is that ―good standards of medical care are the best guidelines in responding to
disasters.‖ This implies that the main challenges of a multiple casualty incident are organizational and
logistic, whereas trauma care remains essentially similar to normal daily practice and is therefore not
an issue.
However, experience from an increasing number of incidents in recent years has shown that this
complicacy is ill advised. A large volume of casualties adversely affects the ability of hospital staff to
provide quality trauma care to the severely injured.
In a major medical disaster, the ability to marshal an effective medical response is so compromised
that trauma care for the severely injured ceases to be an issue. Instead, issues including appropriate
triage, treatment of specific sequel (e.g., crush syndrome after earthquakes), and public health
concerns that threaten entire communities become the focus of attention.
Experienced trauma care providers know from bitter experience that a large casualty load adversely
affects the quality of trauma care given to individual patients. In the military system, it has long been
recognized that in a mass casualty situation conventional standards of medical care cannot be
delivered to all casualties.
REALISTIC HOSPITAL CAPACITY

With proper planning and preparation, a hospital should be able to provide a better medical response
for a multiple casualty incident (MCI) event. However, disaster planners often have a grossly
exaggerated view of the hospital‘s admitting capacity during a multiple casualty incident (MCI).
Calculations are typically based either on the number of beds that can be made available, or on
personnel that can be recruited, without considering the actual quality of care provided to severe
casualties. In real-life incidents, the admitting capacity of a hospital is determined primarily by the
available surgical resources and by the number of trauma teams that the hospital is able to recruit.
196
STAFF DEFINITIONS
Surgeon: Attending surgeons taking trauma calls or chief residents in general surgery capable of
running a trauma team and operating on a casualty independently head the trauma team.
One surgeon performs triage and another is the surgeon in charge of the Emergency Room.
Residents: Surgical residents are part of a trauma team but do not run the case nor operate
independently. One resident is assigned to each group of 12 beds in the Emergency Room
beds area.
MINIMAL ACCEPTABLE CARE
Initially, trauma care provided to non critical casualties in a multiple casualty incident (MCI) is less
than optimal. A patient with a suspected long bone fracture will typically undergo empirical splinting
(without a radiograph) and will be given analgesia. Penetrating chest injuries will be treated by means
of empirical chest tube placement without imaging. Such minimal care along the lines of first aid or
military care buys time, provides symptomatic pain relief, and reduces the risk of complications
without consuming vital hospital resources.
Unfortunately there are currently no guidelines as to what exactly constitutes minimal acceptable
trauma care in a hospital during a multiple casualty incident (MCI). How many hours is it acceptable
to treat a haemodynamically stable patient with a penetrating abdominal injury and a tender abdomen
non-operatively? Should every casualty with a suspected abdominal injury undergo a screening
ultrasound examination to rule out intraperitoneal bleeding? Should the use of the computed
tomography scanner be restricted to patients with severe head injuries and localizing signs or a
deteriorating level of consciousness? Clear guidelines that define what precisely constitutes minimal
acceptable trauma care are an obvious necessity that has not been addressed in detail.
USE OF COMPUTER SIMULATION
The time at which an object changes from state to state is defined as an ―event,‖ hence the term
discrete-event simulation. The discrete-event model is actually a computer programme that moves
objects through the system while keeping track of their flow and interactions. Contemporary visual
simulation packages use a simple graphic user interface that allows straightforward modeling of key
hospital resources and facilities on the computer screen and simulating a series of what-if scenarios.
THE DUAL COMMAND CONCEPT
The Emergency Department is the center of hospital‘s response to a multiple casualty incident (MCI).
Traditional disaster response is based on a single command physician who directs the various teams
operating within the Emergency Department (ED). Current disaster response templates, such as the
Hospital Emergency Incident Command System in California are also based on the concept of a
single medical care director.
The command physician in the Emergency Department (ED) is typically an emergency physician or
surgeon with trauma experience. However, recent experience from the wave of urban suicide
bombings in Israel suggests that a paradigm shift from single command to dual command may be
needed. Effective control of the Emergency Department during a multiple casualty incident hinges on
the coordinated action of 2 command physicians, each responsible for a different sphere of activity.
The volume of administrative, logistic, and clinical information flowing through the Emergency
Department is often too great for a single person to absorb, digest and respond to effectively.
Therefore we propose that 1 command physician should be responsible for the overall medical and
administrative operation of the Emergency Department during a multiple casualty incident, including
patient flow and personnel deployment. This role is best filled by an emergency physician who is
intimately familiar with the normal daily operations of the Emergency Department. A second
command physician is then assigned to supervise the delivery of trauma care. This role, which
includes assigning priorities for surgery and supervising the trauma teams in the trauma resuscitation
area, is best performed by a trauma surgeon if available. (6)
197
GUIDELINES
Several authors have recommended the following guidelines in a mass casualty setting when patient
influx continues and the estimated number of casualties arriving to the hospital is unknown.
1. Perform plain radiographs only when the results will have an immediate impact on
management.
2. Advanced trauma life support should be practiced in the resuscitation shock rooms.
3. There is no role for Emergency Department thoracotomy.
4. Salvageable hemodynamically unstable patients go to the operating room(OR)
5. A focused abdominal sonography for trauma examination is an acceptable method for
detecting abdominal bleeding.
6. CT scans are reserved for patients who have head injury.
7. The use of blood is restricted, with predetermined limits for individual cases.
8. Secondary distribution is practiced: for example, orthopedic fixations and debridement are
transferred out to the surrounding community.
9. Organizational flexibility that allows frequent re-evaluation and retriage of survivors is critical
to screen for commonly associated occult injuries such as pulmonary and intestinal blast
injury, compartment syndrome, ophthalmologic injuries, and delayed vascular compromise.
10. Blast wounds receive extensive irrigation, debridement, and delayed primary closure.
11. Casualty flow is unidirectional.
12. Patient disposition is made by a senior trauma surgeon to ensure appropriate operating room
and ICU use. Stein and colleagues suggest dividing surgical care into two phases; minimal
acceptable surgical care (damage control surgery) while casualties are still arriving and
definitive optimal surgery when new arrivals have ceased. The following priority for operating
room disposition is recommended:
a. haemodynamically unstable patients requiring hemorrhage control
b. Haemodynamically stable patients with the life-threatening torso injuries.
c. Closed head injury with expanding hemorrhage and without extensive brain injury
d. Vascular and orthopedic injuries.
e. Wounds requiring extensive irrigation and debridement.
NEW RECOMMENDATIONS
Based on recent experience with bombing victims, Almology and colleagues have recommended a
modification to the concept of damage control surgery in the unstable trauma patient that includes
packing of multiple entry sites before abbreviated laprotomy and the use of recombinant factor VIIa.
All victims who have multiple fragmented wounds receive total body CT imaging when possible, and
unexplained sepsis or hemodynamic instability results in aggressive evaluation of the abdomen as
the possible source. Also, findings of ―human remains‖ fragments of victims of penetrating blast
injuries has resulted in a guideline mandating hepatitis B immunization for all bombing victims who
have dermal penetration. (7)
CONCLUSION
Planning for multiple casualty situations is typically based on universal principles translated into the
specific circumstances of the hospital, on lessons from disaster drills, and on experience from real-life
incidents. This approach, however, suffers from serious limitations because real multiple casualty
situations are very difficult to analyze retrospectively, whereas disaster drills are conducted within
unrealistic time frames and are often treated with complacency.
A key controversial issue is the realistic institutional capacity of the hospital in a multiple casualty
situation. The Israel Ministry of Health arbitrarily defines this capacity as being 20% of the total
number of hospital beds. (8)
Surgical leadership is required to ensure that critical hospital resources are conserved and applied
appropriately to patient care. A critical challenge to surgeons is balancing their roles as key leaders in
the hospital mass-casualty response against their roles in the operating room. If the expectations
placed on general surgeons are unrealistic, perhaps it is time to consider seriously other alternative
approaches. (7)
198
References:
1. Triage: Techniques & Applications in decision making. Annals of Emergency Medicine Aug 1996 28:2 136-144
2. Einav et al: Annals of Surgery, April 2006 4;243, 538-40
3. The In-House Trauma Surgeon- Paradigm or Paradox, J. of Trauma, April 1992 Vol. 32; 4 413-414.
4. Epidemiological Approach to surgical management of the Casualties of War. BMJ June 1994 Vol. 308 1693-96.
5. Clinical Decision Rules for Secondary Trauma Triage. Annals of Emergency Medicine Feb 2006 Vol. 47 135-145
6. Hospital Trauma Care in Multiple Casualty Incidents: Annals of Emergency Medicine June 2001 Vol. 37;6 647-52
7. Civilian Preparedness and Counter Terrorism: Conventional Weapons. Surgical Clinics Of North America 2006;86
P. 579-600
8. Surgical Resource Utilization in Urban Terrorist Bombing: A Computer Simulation. J. of Trauma Sep 1999 Vol 47
No. 3 545-550.
199
Genitourinary tuberculosis
Dr. A K Sarda, Lovenish Kumar
Causes
The most common pathogen is M tuberculosis.

Uncommonly implicated pathogens include the following:
○ Mycobacterium bovis
o Mycobacterium kansasii
o Mycobacterium fortuitum
o Mycobacterium avium-intracellulare
o Mycobacterium xenopi
o Mycobacterium celatum
Epidemiology
Genitourinary tuberculosis is usually a disease of young to middle age people, involving men more
than women at nearly a 2:1 ratio1. It rarely occurs in children. The true incidence and prevalence of
GUTB are difficult to estimate because many patients remain asymptomatic with respect to
genitourinary tract because the disease is often not looked for in these asymptomatic patients.
Uro-genital TB complicates 3-4% of all cases of pulmonary TB & constitutes at least 39% of all cases
of extrapulmonary disease.2
Medlar3 found bilateral renal cortical lesions in patients with pulmonary TB & suggested
hematogenous spread from the primary lesion in lungs. Colabawala4 in a multicentric Indian study
reported the incidence of TB to be 10 to 34% in patients with various urological diseases. In a study
by the Indian Council of Medical Research (ICMR) in 2240 patients suspected to have GUTB, the
incidence of microbiological &/or histopathological proven diagnosis of TB was 10.7%5
Incidence is highest in persons emerging from Mexico or from Asia, Middle Eastern Africa & South
American countries. Patients with renal TB are uncommon in developed countries, as many as 15-
20% of TB in the developing countries are found with M.Tuberculosis in the urine.6 In 1996, 12
countries, led by India and china accounted for almost 75% of all cases worldwide.7
With the advent of anti-tubercular drugs, there was a decline in the cases of GUTB. Although the
incidence of pulmonary TB rebounded in 1990‘s owing to the Acquired Immuno-deficiency virus
(AIDS) epidemic, adverse socio-economic conditions, & the spread of drug-resistant organisms, there
is scanty evidence that the incidence of GU disease is also increasing. This is especially true about
patients co-infected with HIV. At King‘s County Hospital in NY city, the proportion of patients with TB
at any site who had concomitant GU disease was 37% among AIDS patients & 25% among non-HIV
infected patients (p0.02)8. These patients had more involvement of the kidney, bladder & male
genitalia.
The probability that a HIV infected person who was previously infected with M.Tuberculosis will
develop active TB is 10% per year. In a contrast, a normal host without HIV infection & a similar
M.Tuberculosis experience will have a 5% to 10% lifetime probability of developing active TB.
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Pathogenesis & clinical features
The development of disease depends on the interaction between the pathogen and the immune
response of the host. M.Tuberculosis is the paradigm of successful intracellular pathogen. Although
the organism evokes both a humoral and cellular immune response, it is the latter that determines the
outcome of an infection.10
T lymphocytes interact with mycobacterial antigens to proliferate and to generate low molecular
weight cytokines that, in turn, activate macrophages to become more mycobactericidal. The activated
macrophages become epitheloid cells, which may form into Langhans giant cells. These mononuclear
phagocytes also release a number of factors (TNF-α, TGF-β) that, together with the lymphocyte
secretary products, determine the character of the pathologic lesion & outcome of the infection.
Renal TB is always the result of hematogenous spread of the organism from the lungs. This may
occur at the time of primary pulmonary infection or at the time of secondary infection (reactivation) in
the lungs. With 20% of the cardiac output and the resultant high cortical tension, the kidney is a
favored site for deposition and reproduction of the bacillus. Initial infection occurs in the capillaries of
the renal cortex. A glomerular location is not surprising in view of their high rate of perfusion
(increasing the likelihood of delivering a bacillus in the setting of sparse bacillemia) and their
favorable oxygen tension. Such cortical granulomas usually remain dormant for decades. In some
patients, however, bacillary proliferation within the glomerular capillary leads to capillary rupture and
delivery of organisms into the proximal tubule. Clinically important renal tuberculosis thus is usually
initially localized to the medulla. This is likely caused by entrapment of mycobacteria and infected
macrophage debris within the loop of Henle and the known impairment of phagocyte function
associated with the hypertonic environment found in the medulla.
At this stage, there may be multiple tubercles throughout the kidney. If in course of primary infection,
cell mediated immunity develops and the proliferation of the organism is halted by competent
macrophages, as demonstrated by granuloma formation, fibrous scars can form and harbor the
dormant bacilli for as long as 40 years. With reactivation caused by diabetes mellitus, corticosteroid
administration, old age, and other forms of immunosuppresion, these foci may begin once more to
proliferate. From cases in primary infection was clinically apparent, it is known that the clinical
appearance of renal disease can occur as much as 10 to 25 years later.1
A tuberculoma usually starts as a localized caseating lesion, most commonly in the upper pole of the
kidney, although it may arise anywhere. The caseating granuloma is the classic microscopic finding in
essentially all forms of tuberculosis. Most renal granulomas originate as vascular lesions in the
cortex. Although glomerular lesions predominate, with foci within the capillary tuft, granulomas may
develop within capillaries in relation to the convoluted or collecting tubules. Lesions within the
collecting system per se are usually at the nadir of the loop of Henle or in the pyramidal collecting
tubule, always draining a vascular granuloma, and presumably developing in response to ulceration
and discharge of these lesions into the collecting system. Focal sparing of tubules, glomeruli, or both
within the granulomas is characteristic of renal tuberculosis.
Clinically significant caseation progresses from the medullary collecting system lesions. As the
process of granuloma formation and necrosis progresses, the organisms are shed into the lumens of
the tubules and thereby spread into the deeper regions of the medulla. Here, hypertonicity may impair
macrophage function and allow the continued destructive proliferation of the organism.11 Multiple
microscopic foci coalesce to form larger areas of caseating necrosis or cavitary disease. Progression
to macroscopic lesions soon involves the renal papillae, causing them to slough as well and produce
debris capable of causing caliceal and occasionally ureteral obstruction. Bacilli appear in urine, and
―sterile‖ pyuria is evident. The calices become ulcerated and deformed by both mass lesions and
fibrotic scarring. Once communication with a tuberculous cavity is established, the involved calyx
becomes an ulcerocavernous lesion. Even with treatment, continued fibrous scarring leads to further
distortion of the collecting system architexture. Stenosis and stretching of the calices owing to this
deformation lead to many of the radiographic manifestations.
An important feature of the disease in the kidney is calcification, seen with both progressive necrosis
and healing of lesions. These calcifications are seen plainly on radiographs and can be quite
extensive12. When ureteral obstruction and hydronephrosis occur, the renal parenchyma can be
201
reduced to a thin shell surrounding a large, heavily calcified caseous mass filling the dilated pelvis
and calices- ‗cement‘ or ‗putty kidney‘(pyonephrosis). A total loss of function, called autonephrectomy,
is often the result.
Renal and ureteric stones have been found in upto 19% (Ross 1970)13 patients with tuberculosis. The
destructive lesion occasionally spread outside the renal capsule & produce a mass lesion that can
mimic a neoplasm (Njeh et al. 1993). Rare long standing disease may cause amyloidosis and present
with proteinuria or the nephrotic syndrome.
Many patients with renal tuberculosis remain asymptomatic, and early in the course have no
radiographic signs. The clinical presentation is dominated by patient‘s grave systemic illness.
Summaries of urologic experience stress the higher incidence (as high as 70%) of urologic
complaints including dysuria, flank pain & hematuria.
The most common presenting symptoms in patients with UTB are irritative voiding
symptoms and hematuria, with the reported incidence in world literature at around 60% and 50%,
respectively (Narayan, 1982)15. The patient usually complains of frequent painless micturition, at first
only at night but latter during the day as well. The urine is normally sterile and in a high proportion of
patients. It contains leucocytes. However, upto 20% of patients do not contain leucocytes in their
urine1.
Overt hematuria is present in only 10% of patients but microscopic hematuria is present upto 50%.
Failure of antibiotics to resolve pyuria and lower tract symptoms should lead to consideration of
tuberculous urinary tract infection. Constitutional symptoms such as fever, night sweats & weight loss
are uncommon14. Renal infection may extend into the perirenal or pararenal spaces and/or the psoas
sheath.
202
203
Hypertension may occur as a complication of severe unilateral TB and reduced renal blood flow.
Flechner and Gow (1980) had a reported a twofold-increased incidence of hypertension in patients
with severe renal TB when compared with the incidence in all patients. In the series quoted by
Fletcher and Gow (1980) 64.7% of patients with unilateral nonfunctioning or poorly functioning
kidneys had a fall in blood pressure after nephrectomy16. It is apparent that two thirds of patient, with
extensive unilateral tuberculous nephropathy achieve a substantial fall in blood pressure
after nephrectomy.
Tuberculous interstitial nephritis: Tuberculosis can affect the kidney more insidiously. Advanced
renal failure in which imaging revealed equal sizes small kidneys without evidence of calcification or
gross anatomical distortion have been reported. Renal histology revealed interstitial infiltrates with
chronic inflammatory cells and granulomas; however no tubercle bacilli was seen in the urine nor
grown from it. This emphasizes that there can be tuberculous involvement of the kidneys, sufficient to
cause renal failure, in the absence of either the typical renal destruction with calcification and fibrosis,
or the urinary tract obstruction. (Mallison et al. 1981)17
Tuberculous glomerular disease: No firm link has been established between tuberculosis and
glomerulonephritis although there are a number of case reports including a patient with dense deposit
disease and tuberculosis (Hariprasad et al. 1979)18 and another with military tuberculosis who had
focal proliferative glomerulonephritis (Shriban et al. 1983)19. Chronic tuberculosis sometimes lead to
amyloidosis and in India is not uncommon cause of renal amyloid and renal failure (Chugh et al.
1981)20
Endstage renal disease (ESRD): TB is an important cause of progressive renal failure as, unlike
many other causes of renal failure, it is potentially preventable and treatable (Benn et al. 1988). In
1991, data obtained from the European Dialysis and Transplant Association registry revealed that
195 of 30,064 new patients (0.65%) had renal failure caused by renal tuberculosis. The country with
the highest incidence was Greece (4.51% of new patients), other important contributors being
Portugal, Belgium, Spain, Italy, and Yugoslavia. From published data on primary renal diagnosis from
the United States, Europe, and Australasia, it is clear that tuberculosis is more common in Europe as
a primary renal diagnosis (2247 cases [0.7%]) than in either the United States (0.004%) or
Australasia (0.16%) (Maissonneuve et al. 2000)21. The incidence of UTB as a cause of ESRD is
probably being underestimated. Hence it is important that the diagnosis is considered in all patients
with equal-sized smooth kidneys without a clear cut renal diagnosis, especially in high-risk groups
(Morgan et al.1990)22. Renal biopsy should be considered in such patients.
TB in patients with chronic renal failure and Dialysis: There is a state of relative anergy in uremia
as indicated by skin testing- but the incidence of tuberculous anergy is difficult to assess. The
incidence of anergy is increased by 46% in those on dialysis for 6 years or more. In a study in West
London where there were significant numbers of refugees and asylum-seekers, many of them came
from countries where tuberculosis is endemic, three factors were considered to be important- being
born overseas, the immunosuppressive effect of uremia and the association between diabetes
mellitus & tuberculosis in patients with renal failure (Moore et al. 2002)23
TB is a problem in haemodialysis patients in whom it often presents in an insidious manner with

anorexia, low grade fever and weight loss. Tuberculosis appears to be much more common among
haemodialysis patients than in the general population (Smith 1982)24 and the presentation suggests
that dialysis is associated with reactivation of quiescent disease.
There are fewer reports of tuberculosis among patients undergoing CAPD (continuous ambulatory
peritoneal dialysis) but there is no reason why reactivation of tuberculosis is less likely in these
patients. However tuberculous peritonitis in CAPD patients (Ong et al.1992)25 and peritoneal
tuberculosis (Quantrill et al. 2001)26 have been reported.
Tuberculosis in transplant patients: The disease should be considered when a transplant patient
develops fever, especially from the high risk group. Till late tuberculosis received less attention than
opportunist infections such as those caused by Pneumocystis carinii, Epstein-Barr virus and
cytomegalovirus. It is widely believed that treatment with corticosteroids predisposes to reactivation of
tuberculosis but, surprisingly, there is little published supporting evidence for this belief. In Saudi
204
Arabia, 14 cases were found among 403 renal transplant patients and the annual incidence of
tuberculosis in these patients was about 50 times that of general population (Qunibi et al. 1990)27
Atypical mycobacterial infections
Genitourinary infection caused by atypical mycobacterial organisms is quite rare, although a few cases of
prostatic or epididymal infection, or both, owing to M. kansasii have been reported. In addition, disseminated
disease due to this organism has been reported in immunocompromised patients, with such disseminated
infections seeding the kidney and leading to a granulomatous reaction in the kidney and the isolation of M.
kansasii in the urine. As noted, this form of genitourinary infection is particularly prominent in patients with
AIDS with disseminated infection caused by M. avium-intracellulare and other mycobacterial species.
Tuberculosis of the ureter
The disease (tubercular ureteritis) is always an extension of the disease from the kidney. The advent
of bacilluria leads to distribution of the organism to the ureters and the bladder. The ureteral mucosa
may become ulcerated, thickened, and non-contractile owing to fibrosis of the wall with resultant
pelvi-ureteral junction obstruction, vesicoureteral reflux, and hydronephrosis.
The site most commonly affected is the uretero-vesical junction followed by pelvi-ureteral junction.
The disease is seen rarely in middle third of ureter; occasionally the whole ureter may be involved.
The most common complication is ureteric stricture, may be present at the time of diagnosis of renal
tuberculosis. However it often develops or progresses during effective treatment with anti tuberculosis
drugs. Ureteral colic is uncommon and occurs only if a small flake of calcification or a clot passes
down the ureter.
Keratinizing squamous metaplasia (previously known as leucoplakia) may develop as a late

complication of chronic inflammation and infection of the renal pelvis or bladder, and may persist after
treatment of active tuberculous lesion (Byrd et al. 1976). Keratinizing squamous metaplasia is a risk
factor for the development of squamous carcinoma.28
Tuberculosis of the urinary bladder
Bladder lesions are secondary to renal tuberculosis and bacilluria. The earliest forms of infection start
around one or another ureteral orifice, which become red, inflamed and edematous. Later bulbous
granulations appear and may completely obscure the ureteral orifice. Tuberculous ulcers may be
present, but they are rare and are a late finding. They are irregular in outline, superficial, with a
central, inflammed area usually surrounded by raised granulations. Initially they appear in close
proximity to the ureteral orifices, but later can appear in any part of bladder. Disease progression
leads to muscle eventually replaced by fibrous tissue. This fibrosis starts around the ureteral orifice
which contracts and can either produce a stricture or become withdrawn, rigid and dilated assuming
the classic ‗golf-hole‘ orifice. These ureters become rigid in lower third and give rise to vesicoureteral
reflux.
Occasionally, the whole of the bladder is covered by angry inflamed, velvety granulations with
ulcerations. There can be considerable fibrosis and contraction of the bladder-―thimble bladder‖.
Overt hematuria is present in only 10% of patients but microscopic hematuria is present upto 50%.
Suprapubic pain is a rare presenting syndrome and usually means extensive involvement of bladder.
Suprapubic pain is always accompanied by very frequent micturition. Urgency is uncommon unless
there is extensive bladder involvement. Recurrent cystitis should also alarm for tuberculosis of
bladder.
Tuberculosis of the testis and epididymis
Tuberculosis of the testis is almost secondary to infection of epididymis, which is mostly blood-borne,
because of extensive blood supply of epididymis. Tuberculous orchitis without epididymal
involvement is a rare involvement. It is nearly impossible to differentiate such a swelling from a tumor
and may warrant exploration if rapid response to anti-tuberculosis chemotherapy does not occur.
Hemospermia is a rare presenting symptom.
205
Tuberculous epididymitis may be the first and only presentation of genitourinary tuberculosis.
Tuberculous foci in epididymis are caused by metastatic spread of organisms through the blood
stream. The disease usually starts in the globus minor, because it has greater blood supply than
other parts of the epididymis. It is a disease of young, sexually active males, and in 70% of patients,
there is a previous history of tuberculosis. The usual presentation is a painful, inflamed scrotal
swelling. The globus minor is affected in 40% of the cases; extensive disease may present as
generalized epididymal induration with beading of the palpable vas deferens. Earlier lesions were
bilateral in 34% of cases, but now this presentation is unusual.29 Occasionally a discharging sinus
may be found posteriorly. It is also an important cause of male infertility in affected populations. The
disease causes changes in the seminal fluid composition and thereby adversely influences sperm
motility and agglutination.
Tuberculosis of the prostate
Tuberculosis of the prostate is rare, and in many cases it is diagnosed by the pathologist or is found
incidentally after a trans-urethral resection. Very rarely, the disease spreads rapidly and cavitation
may lead to a perineal sinus. Advanced lesions may cause a reduction in volume of semen, a sign
that may help in the diagnosis. The route of infection may be hematogenous or descending. The
gland is nodular, non-tender and rarely enlarged, with areas of softening being extremely uncommon.
Sometimes, the chronic granulomatous inflammation of the prostate leads to caseation necrosis
which heals by fibrosis or due to poor host defences result in cavitation and sloughing-
―autoprostatectomy‖.30
Tuberculosis of the penis
Tuberculosis of the penis is very rare. Primary tuberculosis of penis occurs after coital contact, with
organisms already present in the female genital tract or by contamination from affected clothing.31
Secondary penile tuberculosis of penis occurs as a secondary manifestation of active pulmonary
tuberculosis. In most cases, the lesion appears as a superficial ulcer of the glans; clinically it is
indistinguishable from malignant disease, although it can progress to cause a tuberculous
cavernositis32 with involvement of the urethra or as cavernositis with ulceration.33
Tuberculosis of the urethra
Tuberculosis of the urethra is also rare. It is caused by spread from a focus in the genital tract. Its
rarity is difficult to understand as there is almost constant exposure of urethra to infected urine. It may
present in either acute or chronic form. In the acute phase, there will be urethral discharge with
involvement of the epididymis, prostate and other parts of the renal tract. The diagnosis is not difficult
in this stage as organism is always isolated. In the chronic form, the diagnosis is difficult because the
disease presents as urethral obstruction or stricture. In such cases, urethral biopsy is required for
confirmation of diagnosis.
Genital tuberculosis
The transmission of genital tuberculosis from male to female is rare. This is quite surprising because
many men with genital tuberculosis have Mycobacterium tuberculosis in the semen. This form of
disease is unlikely to be seen in the developed world but it does appear in developing countries. A
painful swollen inguinal gland in a woman, if it is proven to be tuberculosis, should alert the clinician
to a possible diagnosis of genital tuberculosis in the male partner. Infertilty is also one of the
presentation.
Tuberculosis of the female genital tract
Tuberculosis of the female urogenital tract has been an increasingly rare presentation of TB among
women in developed nations but has remained an important cause of infertility in the developed
world. Genital tuberculosis is the most commonly diagnosed in women of childbearing age from
developing countries who have never been pregnant. In the developing world, approximately 5 to
10% of infertile women are found to have pelvic TB34, and in some regions of India, 19% of infertile
women have been found to have pelvic TB. However it is difficult to establish the true incidence and
206
prevalence of pelvic TB because asymptomatic, latent cases predominate over symptomatic disease.
Overall, the incidence of pelvic TB is decreasing through out the world; it is likely that improved
diagnosis and treatment of pulmonary TB are responsible. In a study performed in late 1980‘s in
India, 37 (60%) of 62 women aged 15 to 45 years with active pulmonary TB had evidence of
unsuspected pelvic TB on laparoscopy. Of these, 15 (41) % of 37 had fallopian tubercles, including
four with coexisting endometrial disease and two with ovarian tubercles.35
Most commonly, pelvic TB occurs after hematogenous spread of M.tuberculosis from a primary
pulmonary site. Approximately 5% of pelvic TB is thought to occur secondary to direct spread from
the bladder, rectum or intestine along the peritoneal surfaces to pelvis. Rarely cervical, vulvar and
vaginal TB may result from direct sexual contact with a partner with TB of the genitourinary tract.
Almost all patients (90% to 100% of patients with pelvic TB) have disease of the fallopian tube, and
both tubes are usually involved. The cause of the predilection of M.tuberculosis is unknown.
The tubes arte thickened, the fimbriated ends of the tubes remain everted, and the orifice remains
patent. With time, the tubes become adherent to the surrounding pelvis structures. Macroscopically,
tubercles on surface are found; microscopically, caseating granulomas can be found. Uterine
involvement is usually limited to the endometrium rather than myometrium. The endometrium may not
exhibit tubercles because monthly sloughing of the endometrium during menstruation does not allow
adequate time for tubercles and caseating granulomas to form. Ovarian pathology demonstrates
parenchymal adhesions. Cervical involvement is generally limited to the endocervical canal.
Vulvovaginal lesions typically present as small, shadow ulcers with sinus tracts and scar formation.
The diagnosis of pelvic TB usually requires a combination of microbiologic, histologic, and

radiographic techniques. Cultures of M.tuberculosis can be obtained endometrial biopsy specimens,
menstrual blood, or less commonly, peritoneal fluid. Histopathologic examination and culture of serial
sections of both fallopian tubes are the most effective means of diagnosing pelvic TB. Radiographic
evaluation usually includes hysterosalpingography water-soluble contrast material and chest radi-
ographs. Hysterosalpingography typically appears abnormal in patients with pelvic TB and may
exhibit the features: multiple constrictions of the fallopian tubes; obstruction of the fallopian tube in the
zone of transition between the isthmus and the ampulla, endometrial adhesions, distortion or even
frank obliteration of the uterine cavity, and, less commonly, irregular calcifications in the adnexal area
or calcified lymph nodes. Occasionally, there may be vascular or lymphatic intravasation.
There has been some concern voiced in the literature that hysterosalpingography should not be
performed for evaluation of pelvic TB because of the risk of disseminating M. tuberculosis into the
abdominal cavity. However, most series do not demonstrate adverse events after this radiographic
procedure.
DIAGNOSIS
1. Tuberculin skin test results are positive in about 90% of patients; but the test does not
clearly distinguish between active tuberculosis, past infection by the tubercle bacillus and
BCG vaccination.
2. Complete blood cell count, sedimentation rate, serum chemistry, and C-reactive protein
studies are helpful to assess severity of disease, renal function, and response to treatment.
3. Chest radiographs may show evidence of active or healed tuberculosis in 50% of patients.
The remainder have normal chest studies.
4. Urine examination
Urine is examined for red blood cells (RBC‘s) & leucocytes and the pH & concentration are
noted. The urine is also cultured for organisms as E.coli. Secondary bacterial is found in 20%
of patients with tuberculosis. Persistent sterile pyuria calls for evaluation for tuberculosis.
Centrifuged samples are stained by Ziehl-Neelsen stain for acid fast bacilli(AFB). Serial early
morning urine (EMU) collection for acid-fast smear (at least 3) is a specific but less sensitive
tool. (Sensitivity is approximately 52% and specificity is 89-96%). EMU specimens are
preferred over 24 hour urine sample because mycobacterial viability falls with prolonged
207
exposure to acid urine. Mild proteinuria (< 1g/24 h) may be seen in as many as 50% of
patients, whereas approximately 15% excrete more than 1g of protein per 24 hours.
5. Microbiological methods
The isolation of Mycobacterium Tuberculosis by urine culture is the definitive diagnostic test
in renal tuberculosis (Sensitivity-65% and Specificity-100%)
Samples are routinely decontaminated by limited exposure to acid or alkaline solutions and
then concentrated by centrifugation. Cultivation usually on solid media, is more sensitive than
microscopy and increases the diagnostic yield by upto 50%. Its disadvantage is the delay,
usually 3-6 weeks, between the receipt of specimen and emergence of visible growth. At
least three, but preferably five, consecutive EMU specimen should be cultured, each onto two
slants:
(i) a plain Löwenstein-Jensen culture medium to isolate Mycobacterium tuberculosis
(ii) a pyruvic egg medium containing penicillin to identify M.bovis, which is partially
anaerobic & grows below the surface of culture medium
Other culture mediums – Kirshner broth (liquid medium)

- Stonebrink
- American Thoracic Society &International Union against Tuberculosis media
- Middlebrook 7H10
BACTEC 460 radiometric system use Middlebrook 7H12 media. It incorporates a 14C-labelled
substrate and during metabolism 14C-labelled carbon dioxide is produced from radio-labelled palmitic
acid and is monitored by the machine. Radiometry indicates the presence of tubercle bacilli within 2-
12 days but the equipment is costly & requires facilities for disposal of radioactive waste.
Mycobacterium Growth Indicator tube(MGIT) – The above said problem has been resolved by the
more recent development of equally rapid automated non-radiometric systems in which bacterial
growth is indicated by changes in color or fluorescence of dyes. In MGIT, the results can be read by
holding the tube over source of UV light.
Other methods:
♦ Luciferase technique- specimens are stained with auramine and rhodamine
♦ Fluorescence technique- fluorescence microscopy can detect low number of mycobacterium
♦ High Performance Liquid Chromatography (HPCL) - reveals qualitative & quantitative differences in
spectrum of mycolic acid in cell walls and is a reliable method for identifying mycobacterial species.
6. Serological diagnosis of TB
Mycobacteria are rich in antigens that stimulate antibody production, and several assays have been
used to detect specific antibody responses in patients with mycobacterial diseases. Enzyme-linked
immunosorbent assay (ELISA) measuring the antibody response to semi-purified mycobacterial
antigens has been most commonly used. Recently, crude antigens have been superseded by more
purified antigens that are specific to certain mycobacterial species. The specificity of serological
assays can also be improved by measuring antibodies directed towards individual antigenic epitopes
by competitive inhibition of the binding of monoclonal antibodies.
A serological test for the diagnosis of TB must be significantly better than Direct Microscopy (i.e.
specificity >99% and sensitivity >70%) to be diagnostically useful. There is at the present time no
serological test that meets these requirements.
7. Polymerase Chain Reaction

Polymerase chain reaction (PCR) is a technique (introduced in October 1985) used to amplify
extremely small amounts of a specific genomic sequence rapidly. The presence of an extremely small
number of bacteria can thus be detected within 24 to 48 hours. Therefore PCR is a promising tool for
rapid detection of urinary tract tuberculosis in urine samples.
In various studies, data show sensitivity ranging from 87-100% (usually >90%) and specificity from
92-99.8% (usually >95%). In an Indian study, 42 patients with suspected genitourinary TB underwent
several diagnostic tests including urinary PCR for M. tuberculosis. Urinary PCR was positive in 81%
208
of cases, urine cultures were positive in 31% of cases, bladder biopsy was positive in 46% and 88%
of IVP was suggestive but not diagnostic.36
The following PCR tests are available with more or less similar quality:
* Genus-specific 16S rRNA PCR test
* Species-specific IS6110 PCR test
* Roche Amplicor MTB PCR test
* Amplified Mycobacterium tuberculosis Direct Detection Test (AMDT)
Along with an accurate clinical assessment, PCR is the best available tool to avoid delay in starting
treatment because it takes only about 6 hours. A PCR vial contains all the necessary components for
DNA duplication: a piece of DNA, large quantities of the four nucleotides, large quantities of the
primer sequence, and DNA polymerase. The polymerase is produced by the thermophilic bacterium
Thermus aquaticus, which was originally found in hot water springs.
8. Imaging Studies
Radiographic evaluation plays a central role in the diagnosis and long term management of patients
with renal tuberculosis.
209
Plain radiographs: They may show calcifications in the renal areas and in the lower urinary tract
(present in up to 50%) as well as other extrapulmonary foci of mycobacterial disease (vertebral,
mesenteric lymph node, adrenal glands) may be present (approximately 10%). It may have variety of
patterns- punctuate, speckled, or hazy. Chest radiographs may show old or active disease in 50% of
patients.
Intravenous Urography: These tests are the standard diagnostic imaging studies for renal TB and are
suggestive of disease in 88-95% of patients. They also help define the extent and severity of disease.
The earliest radiographically detectable changes are cavitary lesions that progress to the papilla and
invade the collecting system, causing calyceal disruption. IVU demonstrate a variety of distortions of
the collecting system from the calices to the bladder. These include cortical fibrosis leading to
distortion, stretching, dilatation (caliectasis), and occlusion of the calices and renal pelvis; obstruction
at any level of the urinary tract; cavitation in the renal parenchyma, with parenchymal and papillary
necrosis leading to filling defects; and masses (tuberculoma) at any level. Non function is manifested
by the absence of a nephrogram in the renal phase of IVU.
Ureteral involvement may include strictures, with or without obstruction; ―corkscrewing‖ or ―beading‖
owing to alternating constrictions and dilatations; pipestem formation (rigid, fibrotic, straight);
ulcerations; hydroureter; and rarely calcification.
Bladder involvement is detected by luminal irregularities caused by ulceration and filling defects
caused by granulomas. It may have thickened, fibrotic walls leading to a markedly diminished
capacity (thimble bladder).
Retrograde Pyelography: It is now rarely necessary, but there are two indications for its use:- First is
a stricture at lower end of ureter, when it is necessary to try to delineate the length of stricture and
amount of obstruction & dilatation above it. Second indication is for ureteral catheterization, which
may be required to obtain urine samples for culture from each kidney if it is not certain from which
side the organisms are coming.
Percutaneous Antegrade Pyelography: It is becoming more important as an alternative to retrograde

ureterography in the cases of a hydronephrotic kidney. It is particularly useful in visualizing a
nonfunctioning kidney or in determining the condition of all excretory pathways above an obstruction.
It can be used to aspirate the contents of the renal pelvis so that they can be sent for diagnostic
examination. Nephrostogram can be performed through the percutaneous nephrostomy tube.
Ultrasonography: It is of limited value in the initial investigation of genitourinary TB. However it is a

non-invasive technique and can be used to monitor kidney lesions found by IVU during course of
chemotherapy. It can show whether a cavity is increasing ordecreasing in size and helps in avoiding
repeated radiographic examinations. Ultrasound may reveal cystic or cavitary lesions, cortical
scarring, hydronephrosis, and abscess in kidneys and is very sensitive in testicular TB. Adnexal
mass, thickened omentum or peritoneum, peritoneal tubercles, loculated or free fluid in the pelvic
cavity, and adhesions are common sonographic findings with female genital TB.
TRUS: In recent years, high-resolution transrectal ultrasonography (TRUS) has become a very useful
noninvasive technique in the evaluation of the subfertile man who has severe oligospermia or
azoospermia associated with a low-volume ejaculate. TRUS can detect abnormalities in the seminal
vesicles and ejaculatory duct and can help assess the status of the prostate. It may show dilatation or
fibrosis of epididymis, atrophy, thickening or calcification of seminal vesicles, or prostatitis.
Cystoscopy & Ureterscopy: It has important place in the evaluation of a patient with suspected
urinary tract tuberculosis, especially when there is haematuria and persistent irritative voiding
symptoms ( frequency, urgency and dysuria). It helps to evaluate the capacity of the bladder, any
obvious bladder lesions and the nature of efflux from either ureter. Above all, bladder biopsy can be
taken. However bladder biopsy is contraindicated in the presence of acute tuberculous cystitis, even if
there are areas of inflammation, either in the bladder or close to the ureteral orifice, that are
suggestive of TB. Biopsy is acceptable only in patients with tubercles or with ulcers some distance
from a normal ureteral orifice, because a diagnosis of carcinoma must be excluded if such lesions are
seen.
210
CT Scan (with contrast)& MRI : This imaging test is a useful adjunct to IVP and is helpful in late or
advanced disease for assessing the extent of disease and the indirect functional status of the affected
kidney compared to the normal opposite kidney. This study is very sensitive for detecting calcification
and thickened walls of the ureter and bladder. Nonvisualization of the affected kidney by excretory
urography indicates advanced disease. CT is of help in intrarenal lesion. CT particularly excels at
demonstrating caliceal involvement, cortical thinning, parenchymal abscesses, and the involvement of
other organs and the retroperitoneum. Magnetic resonance imaging does not appear to offer specific
benefits in the imaging of urinary tract tuberculosis.
♦ Angiography is useful when focal lesions mimic a primary renal mass or when partial nephrectomy
is planned. Angiography also shows obliterated interlobar arteries and avascular lesions.
♦ Renal nuclear scan findings are nonspecific, but they can be used to assess kidney function and to
monitor the effects of therapy.
FUTURE TRENDS
۩ . Nucleic acid probes37

The genetic information of all cells is carried in their deoxyribonucleic acid (DNA). The recent
development in the knowledge of the molecular genetics of mycobacteria has made it
possible to identify particular sequences of DNA that are specific for individual mycobacterial
species. These unique DNA sequences can be detected using labeled oligonucleotides that
are exactly complementary to the nucleotide sequence in the mycobacteria genomic DNA.
Normally, the DNA double helix is very stable, but when it is heated the two chains separate.
Upon subsequent cooling, rehybridization of the two complementary strands occurs. It is,
therefore, possible to use short synthetic and highly specific, single-stranded, labeled DNA
oligonucleotides as probes which will specifically hybridize with the target DNA in the sample.
Such DNA probes can, with high specificity, identify genus or species specific bacterial DNA
sequences. Commercial probes are currently available for identification of several species of
mycobacteria.
۩ . Fingerprinting of mycobacterial strains38

The principle of the method is to extract the mycobacterial DNA from cultured organisms,
digest it with chosen DNA cleaving restriction enzyme(s), and separate the DNA fragments
produced by gel electrophoresis, whereafter certain repetitively occurring DNA sequences
(insertion sequences) are identified by specific probes. This results in a "fingerprint" highly
specific for each individual mycobacterial strain. This molecular genetic identification on the
subspecies level now makes it possible to trace the spread of specific strains (clones) in the
community. In conclusion, identification of specific DNA sequences allows identification of
mycobacterial isolates on genus, species and subspecies level. In fact, each individual
(myco)bacterial strain has its unique pattern, which may be identified and used for
epidemiological studies. Recent outbreaks of multidrug-resistant tuberculosis have been
traced by DNA "fingerprinting"of TB isolates, using restriction fragment length polymorphism
(RFLP) may be even more important.
These techniques may in the near future drastically change the structure of the TB laboratories,
especially in industrialized countries, and will provide new tools for epidemiological studies of
tuberculosis and other mycobacterial infections.
TREATMENT
Medical Management
♦ The antituberculous therapy is the cornerstone in the management of genitourinary tuberculosis; the
multidrug treatment decreases the duration of therapy and diminishes the likelihood that drug
resistant organisms will develop.
♦ The primary aims of treatment are to preserve renal parenchyma and function, to make the patient
noninfectious, and to manage comorbid conditions.
♦ Standard treatment is rifampin, isoniazid, pyrazinamide, and ethambutol for 2 months, then rifampin
and INH for 4 more months unless resistance to either agent exists.
♦ If the resistance exists, Monitor culture and sensitivity reports, and change the regimen accordingly.
211
♦ It is almost impossible to isolate M. tuberculosis from the urine after 2 weeks of chemotherapy.
♦ Indications for prescribing steroids include the following:

• Severe bladder symptoms
• Tubular structure involvement (eg, ureter, fallopian tubes, spermatic cord)
High-dose prednisone (ie, at least 20 mg tid) for 4-6 weeks is recommended because rifampicin
reduces effectiveness and bioavailability of prednisone by 66%.
Surgical Management
♦ If surgery is required, it is scheduled as an elective procedure, and the patient is admitted 6 weeks
after the start of the intensive course of treatment. The aims are
(i) to treat the active disease
(ii) to make the patient noninfectious as soon as possible
(iii) to preserve the maximal amount of renal tissue
♦ Indications for surgery
o Hydronephrosis
o Progressive renal insufficiency secondary to obstruction
o Nonfunctioning or poorly functioning kidneys
o Persistent pain
o Possible neoplasm
♦ Ablative Surgeries
Nephrectomy: Indications are-
1. a non functioning kidney with or without calcification
2. extensive disease involving the whole kidney, together with hypertension and
ureteropelvic junction obstruction
3. coexisting renal carcinoma.
Partial Nephrectomy: Indications are-
1. the localized polar lesion containing calcification that has failed to resolve after 6
weeks of intensive chemotherapy
2. an area of calcification that is slowly increasing in size and is threatening to
gradually destroy the whole kidney.
Nephroureterectomy: only when goal is to remove as much diseased ureter along with the kidney
Abscess drainage: Open surgical drainage (cavernostomy) not indicated now, as with modern
radiographic techniques, the contents of an abscess can be aspirated in a minimally invasive manner.
Epididymectomy & Orchidectomy: Indications are-

1.caseating abscess that is not responding to chemotherapy
2. a firm swelling that has remained unchanged or has slowly increased in size
despite chemotherapy.
♦ Reconstructive surgeries
Ureteral Strictures
Strictures of upper third of ureter:
 DJ stenting
 Endoscopic Dilatation
 Percutaneous Nephrostomy
 Pyeloplasty
Strictures of middle third of ureter:
 DJ stenting
 Davis‘s intubation ureterostomy
Strictures of lower third of ureter:
 DJ stenting
 Ureteral ballon dilatation
 Ureteroneo-cystostomy
 Ileal replacement of the segment in cases of complete stricture
Augmentation Cystoplasty: Indications are-
212
 Intolerable frequency
 Pain
 Urgency
 Hematuria
 Deterioration of renal function by reflux or obstruction
Contraindications are-
 Enuresis
 Incontinence
 Psychiatric disturbances
Urinary diversion: rarely done now for tuberculosis; only three indications-
 A history of psychiatric disturbance or obvious subnormal intelligence

 Enuresis not related to small bladder capacity
 Intolerable diurnal symptoms with incontinence that has not responded
to chemotherapy or bladder dilatation
Approach to a patient with suspected genitourinary tuberculosis
213
Surgical approaches
214
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215
About HIV
Dr. Pawan Lal
History of HIV
Pre-1981
While 1981 is generally referred to as the beginning of the HIV/AIDS epidemic, scientists
believe that HIV was present years before the first case was brought to public attention.
1981 - U.S. Centers for Disease Control and Prevention (CDC) reports first cases of rare
pneumonia in young gay men in the June 5 MMWR, later determined to be AIDS. This
marks the official beginning of the HIV/AIDS epidemic. CDC also issues report on
highly unusual occurrence of rare skin cancer, Kaposi's Sarcoma, among young gay
men in the July 4 MMWR.
New York Times publishes its first news story on AIDS on July 3, 1981
U.S. CDC formally establishes the term Acquired Immune Deficiency Syndrome (AIDS);
refers to four "identified risk factors" of male homosexuality, intravenous drug abuse,
Haitian origin and hemophilia A.
First U.S. Congressional hearings held on HIV/AIDS - "GRID" or "gay-related immune
deficiency" increasingly used by the media and health care professionals, mistakenly
suggesting inherent link between homosexuality and the syndrome.
1983 - The U.S. Public Health Service issues recommendations for preventing transmission
of HIV through sexual contact and blood transfusions.
U.S. CDC clarifies its use of term "high risk group" and urges that it not be used to justify
discrimination or unwarranted fear of casual transmission.
1984 - HIV, the virus, isolated by Luc Montagnier of the Pasteur Institute and Robert Gallo of
the National Cancer Institute; later named the Human Immunodeficiency Virus (HIV).
1985 - First International AIDS Conference held in Atlanta. Hosted by U.S. Department of
Health and Human Services (DHHS) and the World Health Organization (WHO).
1986 - First HIV cases reported in Russia and India. AZT, the first drug used to treat AIDS,
begins clinical trials.
1987 - First antiretroviral drug - Zidovudine or AZT (a nucleoside analog) - approved by U.S.
FDA
1988 - World AIDS Day first declared by World Health Organization (WHO) on December 1
1989 - First guidelines for the prevention of Pneumocystis carinii pneumonia (PCP), an AIDS-
related opportunistic infection and major cause of morbidity and mortality for people
with HIV, are issued by U.S. CDC.
1991 - NBA legend Earvin "Magic" Johnson announces that he is HIV-positive and retires
from basketball. Freddie Mercury, lead singer of the rock band Queen, dies of AIDS.
Red ribbon introduced as the international symbol of AIDS awareness at the Tony
Awards by Broadway Cares/Equity Fights AIDS and Visual AIDS.
1995 - First protease inhibitor, saquinavir, approved in record time by the U.S. FDA, ushering
in new era of highly active antiretroviral therapy (HAART).
2001 - United Nations General Assembly convenes first ever special session on AIDS,
"UNGASS"
2002 - The Global Fund to Fight AIDS, Tuberculosis, and Malaria begins operations
2006 - June 5 marks a quarter century since first AIDS case reported.
Current problem of AIDS
There are estimated to be about 65 million people living with HIV worldwide. The HIV positive cases in
India according to Surveillance for AIDS Cases in India (Period of report - since inception i.e. 1986 to
31 August 2006) – are Males – 88245, females – 36750, total – 124995.
216
Risk/Transmission Percentage No. of cases
categories
Sexual 85.34 106669
Perinatal 3.80 4755
transmission
Blood and blood 2.05 2563
products
Injecting Drug users 2.34 2930
Others (not specified) 6.46 8078
Total 100 124995
Red ribbon history
. Who created the red ribbon?

The red ribbon has been an international symbol of AIDS awareness since 1991. The Red Ribbon
Project was created by the New York based organisation Visual AIDS, which brought together artists
to create a symbol of support for the growing number of people living with HIV in the US.
What does it symbolise?

The red ribbon is worn as a sign of support for people living with HIV. Wearing a red ribbon is a simple
and powerful way to challenge the stigma and prejudice surrounding HIV and AIDS that prevents us
from tackling the global epidemic.
Who owns the red ribbon?

The red ribbon is the result of collaboration between community artists who wanted to create a non-
copyrighted image that could be used as an awareness-raising tool by people across the world.
When did the red ribbon go international?

The first international celebrity to wear a red ribbon was Jeremy Irons at the 1991 Tony Awards. The
symbol came to Europe on a mass scale on Easter Monday in 1992, when more than 100,000 red
ribbons were distributed during the Freddie Mercury AIDS Awareness Tribute Concert at Wembley
stadium. More than 1 billion people in more than 70 countries worldwide watched the show on
television. Throughout the nineties many celebrites wore red ribbons, encouraged by Princess Diana‘s
high profile support for AIDS.
The Human Immunodeficiency Virus (HIV)
HIV belongs to a subset of retroviruses called lentiviruses (or slow viruses), which means that there is
an interval -- sometimes years -- between the initial infection and the onset of symptoms. Upon
entering the bloodstream -- through mucous membranes or blood-to-blood contact -- HIV infects the
CD4+T cells and begins to replicate rapidly. A retrovirus is any of a group of viruses that contain two
single-strand linear RNA molecules per virion, which means it carries its genetic blueprint in the form
of ribonucleic acid (RNA) instead of deoxyribonucleic acid (DNA). Additionally, the enzyme reverse
transcriptase is employed to copy its genome into the DNA of the host cell's chromosomes. Usually
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the cellular process involves transcription of DNA into RNA. Reverse transcriptase makes it possible
for genetic material to become permanently incorporated into the DNA genome of an infected cell.
CD4+T cells are the immune system's key infection fighters and the entity that allows HIV to enter,
attach and infect the body's immune system. The CD4+T cells (also called T4 cells) are disabled and
destroyed by the virus, often with no symptoms, causing a significant decrease in the blood levels of
T4 cells. In the advanced stages of HIV, the body may have fewer than 200 T4 cells, while a healthy
adult's count is 1,000 or more. In this way, the body's immune system is continuously weakened from
the moment of infection and the inability of the immune system to fight infection opens the door to
opportunistic infections.
The HIV Life Cycle

Step 1: Binding
Step 2: Reverse Transcription
Step 3: Integration
Step 4: Transcription
Step 5: Translation
Step 6 - : Viral Assembly and Maturation
Step 1: Binding
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A virus consists of an outer envelope of protein, fat and sugar wrapped around a set of genes (in the
case of HIV, genetic information is carried as RNA instead of DNA) and special enzymes.
HIV has proteins on its envelope that are strongly attracted to the CD4+ surface receptor on the
outside of the T4-cell. When HIV binds to a CD4+ surface receptor, it activates other proteins on the
cell's surface, allowing the HIV envelope to fuse to the outside of the cell.
Entry can be blocked by entry inhibitors for eg. Enfuvirtide, maraviroc (Entry inhibitors work by
preventing HIV from entering healthy CD4 cells (T-cells) in the body. They work differently than many
of the approved anti-HIV drugs—the protease inhibitors (PIs), the nucleoside reverse transcriptase
inhibitors (NRTIs), and the non-nucleoside reverse transcriptase inhibitors (NNRTIs)—which are
active against HIV after it has infected a CD4 cell. Entry inhibitors work by attaching themselves to
proteins on the surface of CD4 cells or proteins on the surface of HIV. In order for HIV to bind to CD4
cells, the proteins on HIV's outer coat must bind to the proteins on the surface of CD4 cells. Entry
inhibitors prevent this from happening. Some entry inhibitors target the gp120 or gp41 proteins on
HIV's surface. Some entry inhibitors target the CD4 protein or the CCR5 or CXCR4 receptors on a
CD4 cell's surface. If entry inhibitors are successful in blocking these proteins, HIV is unable to bind to
the surface of CD4 cells and gain entry into the cells.)
Step 2: Reverse Transcription
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HIV's genes are carried in two strands of RNA, while the genetic material of human cells is found in
DNA. In order for the virus to infect the cell, a process called "reverse transcription" makes a DNA
copy of the virus's RNA.
After the binding process, the viral capsid (the inside of the virus which contains the RNA and
important enzymes) is released into the host cell. A viral enzyme called reverse transcriptase makes a
DNA copy of the RNA. This new DNA is called "proviral DNA."
Reverse transcription can be blocked by: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) for
eg. Zidovudine, lamivudine, emtricitabine, abacavir, tenofovir disoproxil fumarate (tenofovir DF),
didanosine, stavudine and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) for eg.
Delavirdine, efavirenz, nevirapine.
(NRTIs, sometimes referred to as "Nucleoside Analogues" – or "nukes" for short – prevent healthy T-
cells in the body from becoming infected with HIV. When HIV infects a cell in a person's body, it
copies it's own genetic code into the cell's DNA. In this way, the cell is then "programmed" to create
new copies of HIV. HIV's genetic material is in the form of RNA. In order for it to infect T-cells, it must
first convert its RNA into DNA. HIV's reverse transcriptase enzyme is needed to perform this process.
NRTIs contain faulty versions of the building blocks (nucleotides) used by reverse transcriptase to
convert RNA to DNA. When reverse transcriptase uses these faulty building blocks, the new DNA
cannot be built correctly. In turn, HIV's genetic material cannot be incorporated into the healthy
genetic material of the cell and prevents the cell from producing new virus.)
(NNRTIs, sometimes referred to as "Non-Nucleoside Analogues" – or "non-nukes" for short – prevent

healthy T-cells in the body from becoming infected with HIV. When HIV infects a cell in a person's
body, it copies it's own genetic code into the cell's DNA. In this way, the cell is then "programmed" to
create new copies of HIV. HIV's genetic material is in the form of RNA. In order for it to infect T-cells,
it must first convert its RNA into DNA. HIV's reverse transcriptase enzyme is needed to perform this
process. NNRTIs attach themselves to reverse transcriptase and prevent the enzyme from converting
RNA to DNA. In turn, HIV's genetic material cannot be incorporated into the healthy genetic material
of the cell, and prevents the cell from producing new virus.)
Step 3: Integration
The HIV DNA is then carried to the cell's nucleus (center), where the cell's DNA is kept. Then, another
viral enzyme called integrase hides the proviral DNA into the cell's DNA. Then, when the cell tries to
make new proteins, it can accidentally make new HIVs.
Integration can be blocked by integrase inhibitors, a new class of drugs that are in the earliest stage of
research. For eg. raltegravir , elvitegravir .
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(After the "reverse transcription" of RNA into DNA is complete, HIV's DNA must then be incorporated
into the T-cell's DNA. This is known as integration. As their name implies, integrase inhibitors work by
blocking this process. Integrase inhibitors may offer a lot of hope for HIV-positive people, especially
those who have developed HIV resistance to drugs that target HIV's two other major enzymes:
reverse transcriptase and protease. Even though integrase inhibitors have been studied for several
years by pharmaceutical companies and researchers, very few have made it into advanced clinical
trials. However, two have made it and are showing promise in clinical trials: Gilead Science's GS-
9137 - elvitegravir (phase II studies) and Merck's MK-0518 - raltegravir (phase III studies).
Step 4: Transcription
Once HIV's genetic material is inside the cell's nucleus, it directs the cell to produce new HIV.
The strands of viral DNA in the nucleus separate, and special enzymes create a complementary
strand of genetic material called messenger RNA or mRNA (instructions for making new
HIV).Transcription can be blocked by antisense antivirals or transcription inhibitors (TIs), new classes
of drugs that are in the earliest stage of research. For eg. 4-Phenylcoumarins, Temacrazine
Step 5: Translation
The mRNA carries instructions for making new viral proteins from the nucleus to a kind of workshop in
the cell. Each section of the mRNA corresponds to a protein building block for making a part of HIV.
As each mRNA strand is processed, a corresponding string of proteins is made. This process
continues until the mRNA strand has been transformed or "translated" into new viral proteins needed
to make a new virus.
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Step 6 - : Viral Assembly and Maturation
The final step begins with the assembly of new virus. Long strings of proteins are cut up by a viral
enzyme called protease into smaller proteins. These proteins serve a variety of functions; some
become structural elements of new HIV, while others become enzymes, such as reverse
transcriptase.
Once the new viral particles are assembled, they bud off the host cell, and create a new virus. The
virus then enters the maturation stage, which involves the processing of viral proteins. Maturation is
the final step in the process and is required for the virus to become infectious.
With viral assembly and maturation completed, the virus is able to infect new cells. Each infected cell
can produce a lot of new viruses. Viral assembly can be blocked by Protease Inhibitors (PIs) for eg.
Amprenavir, tipranavir, indinavir, saquinavir, fosamprenavir, ritonavir, darunavir, atazanavir, nelfinavir.
Maturation, a new target of companies developing anti-HIV drugs, may be blocked using Maturation
Inhibitors. For eg. bevirimat, hydroxyurea
(Protease inhibitors prevent T-cells that have been infected with HIV from producing new copies of the
virus. When HIV infects a cell in a person's body, it copies it's own genetic code into the cell's DNA. In
this way, the cell is then "programmed" to create new copies of HIV. Once HIV's genetic material
(RNA) is inside a T-cell's DNA, the cell produces a long strand of genetic material that must be cut up
and put together correctly to form new copies of the virus. Cutting up this strand requires a scissor-like
enzyme called protease. PIs block this enzyme and prevent the cell from producing new viruses.)
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Aids stands for:
Acquired which means:

 you were not born with the disease compared to most immune deficient conditions
*You can only be born with AIDS if your mother had AIDS when pregnant
Immunodeficiency which means:
 the disease is characterized by a weakened or ineffective immune system with no resistance
to infections
Syndrome which means:
AIDS is a combination of signs and symptoms which occur together due to the HIV infection
as well as many other infections as a result of the immunodeficiency
The definition of AIDS relates to:

CD4+ T-cells Count:
 Healthy adults usually have CD4+ T-cell counts of 1,000 or more
 Aids and some HIV sufferers have less than 200 CD4+ T-cells
HIV Virus spreads by

Sexual Contact
The virus can be spread in:
 Artificial insemination with semen from an infected person
 Body fluids including sperm
 Oral sex
The infection can be spread from unprotected sex (sex without condoms) with an infected
partner, including:
 anal intercourse
 oral intercourse
 vaginal intercourse
and is spread from:
 men to men
 men to women
 women to men
 women to women
The virus can enter the body during sex through the:
 lining of the vagina
 mouth
 penis
 rectum
 vulva
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HIV Antibody Testing Options
Blood is normally tested first using the ELISA test. It‘s quite cheap, and also has the advantage of
being very sensitive. Provided the test is performed long enough after your exposure to HIV for
antibodies to appear (for almost everybody, this is three months), the ELISA test will almost certainly
detect them. Two terms are used to describe the accuracy of tests: ‗sensitivity‘ and ‗specificity‘. The
ELISA test is very sensitive (99.5 per cent) meaning it will detect even very small quantities of HIV
antibodies. But, because the ELISA test is so sensitive, it has less specificity which means there‘s a
chance that it could produce a small number of false-positive results. Because of this a second type of
HIV test, the Western Blot, is performed on all samples that test positive for HIV antibodies using the
ELISA test. The Western Blot test confirms if a sample is positive or negative. Very rarely, a result
comes back ‗indeterminate‘, meaning a person has just started to develop antibodies to HIV because
it is so close to the time when they were infected. If this happens, the person will need to be re-tested
outside the three-month window period it can take for HIV antibodies to develop. False-positive tests
are exceedingly rare after a Western Blot test.
Standard blood test: This was the first HIV antibody test developed and made available, and is the
most widely used. With this test, an initial assay is used (the ELISA), and confirmed using a more
specific test (the Western Blot).
Oral mucosal transudate test:- This test, an alternative to the standard blood test, uses a specially
treated pad placed in a person‘s mouth, and gently rubbed between the lower cheek and gum. The
pad collects an oral fluid called oral mucosal transudate (OMT). This fluid contains HIV antibodies in
an HIV- infected person. This test does not test for HIV in saliva.
Urine HIV antibody test: The urine HIV-1 testing method is a painless, non-evasive option for getting
an HIV antibody test. This test uses the urine EIA (ELISA) and urine Western Blot technique to detect
HIV antibodies, and is FDA – licensed as an alternative to the blood test system. This test eliminates
accidental needle sticks and exposure-related dangers, protecting the patient and healthcare worker.
Rapid HIV antibody tests: Where the standard HIV antibody testing procedure requires up to two
weeks for results, the rapid test gives results in 5-60 minutes. Currently approved rapid HIV tests only
test with blood. Other rapid HIV testing methods are in development. To perform the test, a
fingerstick sample of blood is collected from an individual and transferred to a vial where it is mixed
with a developing solution. The test device, which resembles a dipstick, is then inserted into the vial.
In as little as 20 minutes, the test device will indicate if HIV-1 antibodies are present in the solution.
Other tests for HIV
Other types of HIV tests are available, called HIV RNA tests. Rather than looking for antibodies,
these tests look for the actual virus. Several tests are available, including amplicor, bDNA and
NASBA. These are routinely used to monitor people with HIV infection, find out their risk of disease
progression and monitor the effect of anti- HIV therapy. These tests are not routinely used to check for
HIV infection. First, they cost a lot more than antibody tests. Second, a number of problems occur
when using them to screen for the presence of HIV. The major problem is that they have a significant
false positive rate. That means the test sometimes suggests that someone is infected when in fact
they are not. Using these tests to screen for HIV has caused people emotional unrest. As well,
antibody tests are more than 99.9% accurate.
Voluntary Counselling and Testing
Voluntary HIV counselling and testing is the process by which an individual undergoes counselling
enabling him or her to make an informed choice about being tested for HIV. This decision must be the
choice of the individual and he or she must be assured that the process will be confidential. However,
in concurrence with the Supreme Court decision, Partner notification is necessary and this makes it
imperative for the attending physician to disclose the HIV status to the spouse or sexual partner of the
person. Inspite of this all efforts must be made to counsel the person for disclosure of HIV status to
the spouse or sexual partner.
When to declare HIV positive : In voluntary counselling and testing centers the following procedures
should be practiced
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The serum sample is first tested with one ELISA or Simple/Rapid assay. Any reactive sample is
retested using a different assay. Serum found reactive on the second assay is repeated for the third
test.
Serum found reactive on all the three tests is considered HIV antibody positive.
Indeterminant result- serum that remains discordant in the second assay or reactive on the 1st And
2nd test but non-reactive on the 3rd test is considered to be indeterminate. In such cases, the person
must be asked to report for a re-test after a minimum period of 2 weeks and if still indeterminate may
be subjected to a confirmatory assay like Western Blot or Line immunoassay. In some cases the
person may be followed up for 3,6 or 9 months.
Counselling Process
The VCT process consists of the following-

Pre test Counselling
Post test counselling
Follow-up counseling
The contents and approach of each type of counselling may vary and should be adapted to the needs
of the clients and may be different for individuals, couples, families, men, women etc. Contents and
approaches may also reflect the context of intervention, eg. Counselling associated with specific
interventions like MTCT.
Counselling as part of VCT ideally involves at least two sessions ( pretest and post test counselling).
More sessions can be offered before and after the test or during the time the client is waiting for the
test result.
(1) Pretest Counselling
HIV counselling should be offered before taking an HIV test. In this process the counselor
prepares the client for the test by explaining what an HIV test is and also by correcting
myths and misinformation about HIV/AIDS. This counselling can also be provided to
groups to reduce costs and can be backed up by providing printed information. However,
group counselling must be followed by individual sessions before the HIV test is
undertaken.
Persons refusing pre-test counselling should not be prevented from taking a voluntary
HIV test. But informed consent from the person being tested is usually the minimum
requirement before an HIV test.
(2) Post test Counselling
Post test counselling should always be offered. The idea is to help clients to understand
their test results and initiate adaptation to their seropositive or seronegetive status.
When the test is seropositive, the counselor tells the client the result clearly and
sensitivitely, providing emotional support and discussing how he/she will cope. The
counselor must ensure that the person has immediate emotional support from a partner,
relative or friend. Sharing one‘s HIV status with a sexual partner is important to enable the
use of safer sexual practices. And should be encouraged.
Counselling is also important when the test result is negetive. While the client is likely to
feel relief, the counselor needs to discuss changes behaviour that can help the client to
stay negetive. The window period of HIV testing means that the patient may not be truly
negetive and the client may be asked to undertake the test again in 3 months time,
depending on the history of risk behaviour.
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Follow-up Counselling
Most of the persons may require follow-up counselling immediately after post test counselling or
anytime between 1 to 5 years following post test counselling. This often coincides with a crisis or
change in personal circumstances. VCT services should therefore be flexible and either be able to
provide ongoing counselling or have close links with other organizations for referral like community
organizations, spiritual groups or health facilities.
As part of follow-up counselling, the VCT services should offer the opportunity of ongoing care and
support for seropositive cases and should act as an entry point to medical care. Collaboration and
cross referral can ensure that people with HIV receive appropriate medical care., including home care
and supportive palliative care.
Counselling of women in antenatal settings for MTCT ( Prevention of mother to child transmission)
interventions special consideration should be given to
Counselling about infant feeding
Counselling about MTCT options
Family planning counselling
Counselling about partner notification
Involvement of partner in decision making
AIDS RELATED OPPORTUNISTIC INFECTIONS AND MALIGNANCIES

1. Pneumocystis carinii Pneumonia
A. cause -- Pneumocystis carinii (parasite)
B. site -- typically lungs, has been seen in eyes
C. symptoms -- high fever, dry cough, shortness of breath
D. diagnosis -- induced sputum, bronchoscopy, open lung biopsy
E. treatment --
1. Bactrium (IV or oral), a.k.a. Septra, TMP/SMX
2. Dapsone (oral)
3. Pentamidine (IV)
4. Atovaquone (oral)
5. Trimetrexate (oral)
F. prophylaxis (preventive treatment) --
1. Bactrim (oral)
2. Aerosolized Pentamidine
3. Dapsone (oral)
2. Toxoplasmosis
A. cause -- Toxoplasma gondii (parasite)
B. site -- brain
C. symptoms -- fever, headache, neurologic changes
D. diagnosis -- toxoplasma antibody (blood test), CT scan of brain
E. treatment
1. pyramethanine/sulfadiazine orally
2. Clindamycin/pyramethamine
3. Cryptosporidiosis
A. cause -- cryptosporidium (parasite)
B. site -- colon
C. symptoms -- severe diarrhea, cramping, weight loss
D. diagnosis -- stool cultures, biopsy from colon
E. treatment
1. none proven effective
2. possibly diclazuril orally
3. possibly spiramyacin orally or IV
4. attempt to slow diarrhea with various medications
4. Candidiasis
A. cause -- Candida albicans (yeast)
B. site -- mouth, vagina, esophagus (throat), GI tract
C. symptoms -- white patchy growth, painful swallowing, fever
D. diagnosis -- examine scrapings under microscope, biopsies
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E. treatment --
1. Ketoconazole (Nizoral) orally
2. Nystatin swish in mouth
3. Mycelex troches
4. Amphotericin B IV
5. Fluconazole orally/IV
F. prophylaxis --
1. Nizoral orally
2. Fluconazole orally
5. Cryptococcal meningitis
A. cause -- Cryptococcus neoforms (yeast)
B. site -- meninges (the covering of the brain and spinal cord)
C. symptoms -- fever, headache, difficulty touching chin to chest
D. diagnosis -- culture of spinal fluid obtained via lumbar puncture
E. treatment --
1. Amphotericin B IV
2. fluconazole IV or orally
F. prophylaxis --
1. fluconazole orally
6. CMV retinitis/colitis
A. cause -- cytomegalovirus (virus)
B. site -- eye (retinitis), colon (colitis), lung (pneumonia)
C. symptoms -- visual changes, diarrhea, fever, difficulty breathing
D. diagnosis -- visual exam of retina; biopsy of colon, lung
E. treatment --
1. ganciclovir IV
2. foscarnet IV
7. Progressive multifocal leukoencephalopathy (PML)
A. cause -- viral infection, possibly associated with JC virus
B. site -- multiple locations of white matter in the brain
C. symptoms -- rapid neurological changes, varies by location of PML
D. diagnosis -- CT scan, MRI scan, biopsy of lesion
E. treatment
1. AZT with alpha-IFN
8. Mycobacterium avium complex (MAC), also known as MAI

A. cause -- Mycobacterium avium intracellulare, other mycobacterium
B. site -- disseminated: lungs, bone marrow, lymph nodes, blood
C. symptoms -- fever, weight loss, anemia, diarrhea
D. diagnosis -- blood and sputum cultures, biopsy from bone marrow
E. treatment --
1. rifampin
2. ethambutol
3. Ciproflaxin
4. clofazamine
5. rifabutin, also IV Amikacin
F. prophylaxis -- rifabutin
9. Mycobacterium tuberculosis
A. cause -- Mycobacterium tubercule
B. site -- lungs, disseminated
C. symptoms -- chronic cough, bloody sputum, fever
D. diagnosis -- PPD skin test, chest X-ray, sputum culture
E. treatment --
1. INH
2. rifampin
3. ethambutol
F. prophylaxis -- INH for one year if PPD positive
10. Kaposi's Sarcoma
A. cause -- uncertain, possibly herpes-related virus (KSHV)
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B. site -- skin, lymph nodes, lungs, mouth, GI tract
C. symptoms -- slightly raised purplish lesions, usually painless
D. diagnosis -- biopsy of suspected lesion, endoscopy to biopsy internal lesions (colonoscopy,
bronchoscopy, upper endoscopy)
E. treatment --
1. Isolated lesions usually not treated
2. Radiation of single lesion for cosmetic purposes
3. Treatment usually initiated if multiple lesions or internal lesions noted
4. Combination cancer chemotherapeutic (usually IV)
5. Local injections of chemotherapeutic agents or interferons
6. Surgical excision of tumors if needed
7. Cryotherapy (freezing) of single lesions
11. non-Hodgkin's lymphoma
A. cause - unknown, is a form of cancer
B. site -- brain, lymph nodes, GI tract
C. symptoms -- depends on location, may note large tumor on X-ray
D. treatment --
1. combination cancer chemotherapy
2. localized radiation
3. surgical excision of tumor
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Transmission of HIV
Dr. Sudha Salhan
The burden of HIV infection includes not only expenditures on care, direct medical costs but also
the cost of lost productivity due to illness and shortened lifespan.
According to USAIDS 2006 Report on the global AIDS epidemic 39.5 million people are living
with HIV world wide. Highest being in sub Saharan Africa (5.9%)
By now we all know how Human Immuno Deficiency virus (HIV) is transmitted. HIV attacks
immune system as a tentivirus, a subfamily of the retrovirus. Retrovirus are RNA viruses that
contain the reverse transcriptase enzyme (RTE). RTE catalyzes the synthesis of DNA from an
RNA template (i.e. reverse of normal viz RNA from DNA) This haploid double st r and DNA
provirus get inserted into the chromosomal DNA of the host cell. When the cell is activated,
transcription and translation occur allowing the assembly of viral proteins necessary for the
production of virions that are released to infect other cells. HIV has a high repliation and a high
mutation rate and hence a patient may harbour a number of variants which may post problem for
vaccine development and Ante Retroviral Treatment (ART).
HIV infected cells may undergo lysis due to virus replication and budding. If the infected cells
does not undergo lysis, other normal or infected cells can stick to it due to the presence of
envelop proteins. These cells may fuse and form giant cell progeny carry proviral DNA. Infected
CD4 cells can undergo apoptosis thus decreasing CD4 count.
Human cells and tissues susceptible to HIV as shown by invitro and invo study.
Haematopoietic system
T lymphocytes Dendrtitic cells
B lymphocytes Promyelocytes
Macrophages Stem cells
NK cells Tynmic epithelium
Mega karyocytes Follicular dendritic cells
Brain Capillary endothelial cells Choroid plexus
Astryocytes Ganglia
Macrophages (Microglia) Neuroblastoma cells
Oligodendrocyte Glinone cells lines
Skin Fibroblasts & Langerhan‘s cells
Bowel Columner epithelium and goblet
cells
Others – Mlyocardiam, renal tubuler cells, hepatic sinusoid epithelium, kupffer cells, pulmonary
fibroblasts, retina, prostate, testes, foetal chorionic villi, placeral trophoblast cells, fetal adrenal
cells etc
HIV practically multiples in all cells but the extent of replication varies in different cells.
Modes of transmission of HIV.

Ever 6.4 second one person in infected with HIV
The ways in which HIV is transmitted have been clearly identified by research.
Shown in the table provided by National AIDS Control Organization (NACO)
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Table: Efficacy of different routes of HIV transmission and their contribution to total number of
cases
Exposure Route Efficiency % of total India
(World over)
Blood transfusion 90-95% 5 5.5
Perinatal 20-40% 10 0.7
Sexual intercourse 0.1-1.0% 75 -
vaginal (male or female) 01-0.2% 60 80
Anal (male to male) 0.3-10% 15 -
IDU 0.5-1.0% 10 5.2

Needle stick exposure 0.5% 0.1
Others - - 7.5
The other categories include organ transplantation, tattooing, ear piercing etc.
The most efficient vehicle of HIV Transmission is blood (90-95%). The risk of HIV transmission by
blood and from whole organ donation of an HIV infected donor is nearly 100%. Fresh frozen
unprocessed bone from an infected donor has a higher risk. If marrow elements or tissues are not
removed. Vascular solid tissue pose a lower risk of HIV transmission if processed by techniques that
might have inactivated the HIV.
Persons may become infected by receipt of blood, organ and tissues from donors who are in the
‖window period‖ and hence have tested seronegative by ELISA during the period of donation.
However, the risk of infection via blood transfusion is now extremely low due to strict HIV screening of
donated blood.
The most common route of transmission is unprotected penetrative sexual contact. The efficacy is
0.1-1% only. But due to repetition it is the usual method seen.
The chances are higher when other well defined risk factors are also present like multiple sex
partners, presence of STD‘s e.g. genital ulcers (allowing direct exposure to HIV burden blood), Sex
with person from high HIV infections or high risk behaviours (e.g. IUD‘s) Non ulcerative STDs like
gonorrhea and chlamydia also facilitates transmission nearly 3 times compared with a woman with no
STD.
Other factors are genital trauma (forced intercourse or anal intercourse) an exposure to blood during
the act (e.g. during the time of menses) lack of male curcumcision with AIDS having high
concentration of HIV.
Behaviour factors like use of alcohols other addictive drugs impair judgement and may lead to risky
sexual behaviours increasing probability of transmission.
Mother to Child Transmission now called Parent to Child transmission occur before, during birth
and after birth by breast feeding.
Perinatal (vertical) transmission HIV can be transmitted (20-45%) from mother to the foetus in
utero.
Time of transmission can be intra uterine (HIV is isolated from aborted fetuses).
During delivery- This makes the maximum infection period (65-80%). Postpartum by breast feeding
(10-14%).
Factors increasing vulnerability to Parent to child transmission

- Viral load maximum immediately after infection and advanced stages.
- Smocking and illicit drugs use by the mother
- Concurrent STI
- Unprotected sexual intercourse
- Maternal CD4 and lymphocyte count
- Nutrition status of the mother.
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- Mothers on ART have less chances of HIV transmission
- Vaginal delivery in mothers with No ART is more dangerous (then CS is better) compared to
in mothers on ART.
- If membranes are ruptured for more than 4 hours before delivery.
- Episiotomy procedures during labour
- Cord blood sampling, scalp blood sampling etc.
- Foetal factor – Preterm foetus
- Breast feeding - no breast feeding is best. Exclusive breast feeding is next best. But mixed
feeding make the infant more prone to HIV infection
- Duration of breast feeding
Injection drug users use unsterile needles, and syringes and also inject among themselves that
causes rapid transmission. It is common in eastern region e.g. Manipur.
Injecting drug use is a major risk factor and in many parts of the developed world it contributes more
to the number of cases than hetrosexual or homosexual acts factors contributing to HIV transmission
among IDUs
- Drug injection practices (they sit in a circle and with the same needle and syringe keep on
injecting by turn)
- Sexual behaviour
- Presence of STDs
- Increase of addictive drugs. Among IUD‘s HIV infections progress more rapidly to AIDS with
increasing age.
Transmission in health care setting- Health care personnel (HPL) refers to all paid and unpaid
persons working in health care setting, who have the potential for exposure to infections materials
(e.g. blood , tissue and specific body fluids etc.) An exposure that might place HPL at risk for HIV
infection is defined as percutaneous injury (e.g. a needle stick or cut with a sharp object) or contact
of mucous membranes or nonintact skin (e.g. exposed skin that is chopped, abraded or afflicated
with dermatitis) with blood, tissue or other body fluids that are potentially infectious. In addition to
blood and visibly bloody body fluids, semen and vaginal secretions are also considered potentially
infectious. Other fluids considered potentially infections are CSf, synovial fluid, pleural fluid, peritoneal
fluid, pericordial fluid and amniotic fluid. Faeces, nasal secretions, saliva, sputum, sweet, tears, urine
and vomitus are not considered potentially infectious unless they are visible blood.
The risk varies with the type and severily of exposure. After percutaneous exposure to HIV infected
blood approximately 0.3%. After a mucous membrane exposure approximately 0.09% other exposure
are not quantified.
Multiple factors affecting the risk of HIV transmission in health care worker
- Larger quantity of blood
- A device (needle) directly in a vein or artery
- Blood visibly seen on the needle.
- Deep injury (Hallow bore needle)
- Terminally ill HIV patients (more HIV titre)
- Viral load of the patient.
- Selection of HIV PEP regimens. As soon as possible, preferably with in hours rather than
days of exposure.
- The drugs must balance the risk of infection against the potential toxicity of the agents used.
Factors influencing transmission include

- Amount of virus in the body fluid
- Extent of contact
- Multiple homosexual or hetrosexual
- Partners
- Failure to use condoms
- Existing sexually transmitted disease
- Cervical ectopy in young women
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Information about primary HIV infection indicates that systemic infection does not occur
immediately, leaving a brief window of opportunity during which post exposure antiretroviral
intervention might modify or prevent viral replication. Infection of dendritic like cells occurred at
the site of innculation during the first 24 hours following mucosal exposure of cell free virus over
the subsequent 24-48 hours. Migration of those cells to the regional lymph nodes occurred and
virus was detectable in the peripheral blood with in 5 days. Theoritically, initiation of antiretroviral
PEP, soon after exposure might prevent or inhibit systemic infection by limiting the proliferation of
the virus in the initial target cells or lymph nodes.
In health care setting rarely workers have been infected with HIV after being stuck with needles,
containing HIV infected blood or less frequently after infected fluid gets into workers open mucous
membranes (eyes or mouth or nose)or cut in the body viceversa patient infected by a health care
worker. Out of 22, 000 HIV infected physicians, surgeons dentists, in USA only one example of six
patients infected by a HIV positive dentists was there.
HIV is NOT transmitted through Air, water or insects. HIV is a fagile virus and does not survive well in
the environment. Drying of high concentration of HIV reduces the infectioness by 90-99% with in
several hours.
Cannot get HIV by

- Casual physical contact
- Coughing, sneezing and social kissing
- Sharing utensils or consuming food and beverages handled by someone who has HIV.
- Sharing toilet and washing facilities.
- Sharing linen and bed
- Shaking hands, nursing care with intact skin
- Mosquito and other insect bites.
There is no risk of HIV transmission to coworker and patients in food service establishment.
Kissing – Casual contact through kissing through closed mouth is no risk. Biting may rarely cause
HIV transmission in the presence of blood (ulcer or injury to lips or mucous membrane of
mouth).
Saliva, tears and sweet –contact with saliva tears or sweet has NEVER been shown to result in
transmission of HIV. Saliva in adults contains some nonspecific inhibitory sustain like
firbonectins and glycopropteins which could prevent cell to cell transfer of virus. Thus saliva is
not a likely vehicle of transmission have been reported to yield zero or a few HIV particles.
Hence these vehicles also donot appear to be important in virus
Insect bite is harmless. HIV lives for only a short time inside the insect. It does not reproduce in
insect. Insect is hence not infected and cannot transmit HIV to the next human in feeds on or
bites.
Cannot penerate unbroken skin.
HIV transmission during early infection
Nearly half of HIV transmission occurs less than 6 months after serocanversion.
The early stages of HIV infection are characterized by a high viral load in the blood and semen which
enhances the risk of its transmission. Knowing the amount of HIV transmission during early infection
is important for developing prevention strategies.
Prompt detection of persons newly infected with HIV followed by counseling to reduce risk behaviour
is essential for reducing future transmission reduction of viral load with drugs also reduce
transmission danger (Brenner BG et al 2007)
High rates of forward transmission events after acute (early HIV I infection J Infect Dis 2007, 195-95)
Pilley D & Fisher M. Primary HIV infection, polylogenetics and antiretroviral prevention J infect dis
2007, 195,924.
If women infected with both HIV and HSV are treated with valacy clovir it significantly reduces plasma
HIV-1 RNA levels and as well as the frequency of HIV1 shedding and quantity of HIV-1 RNA in genital
secretion. This reduces transmission of HIV.
232
Published in physician‘s First watch Feb 22, 2007.
Dual HIV and malaria infection potentials the spread of both diseases.
In an HIV infected individual acute malarial infection loads to a viral load spike that could potentially
increase the likelihood of HIV transmission (Acc March 1, 2006)
Treating HIV positive patients with ART could reduce the rate of HIV transmission by as much as
70%(Monaneer et al 2006)
JS Montaner, Hogg R, Wood E et al. The case for expanding access to highly active ART to curb the
growth of the HIV epidemic. The Lancet 368 (9534) 531, Aug 16,2006.
Treatment of an exposed site wounds and skin sites that have been in contact with blood or body
fluids should be washed with soap and water. Mucous membranes should be flushed with water.
Squeezing the wound further reduces the risk of blood born pathogen transmission, however the use
of antiseptics in not contraindicated. The application of caustic agents (e.g. bleech or the infection of
antiseptic or disinfectants into the wound is not recommended.
Exposure Report The causality department is reported the circumstances and the post exposure
management done there.
- Date and time of exposure

- Details of the procedure being performed and injury so caused
- Details of exposure type and amount of fluid
- Whether the exposed source material contained HIV
- Detailed about exposure person –vaccinated for Hep B and take test with in hours
- Detailed of counseling post exposure management and follow up
- Evaluation of the exposure source inform and take test within hours.
If HIV positive state asymptomatic or symptomatic with AIDS.
233
Prevention of HIV Infection
Dr. V J Anand, Debabrata Roy
To grasp the significance of prevention of HIV infection, one must have an accurate idea of the
statistics of the cases and means of spread. As surgeons, we also need to have understanding about
Universal Work Precautions so that proper precautions can be taken at the work place to prevent the
spread of HIV in hospital settings. The write-up will be incomplete without mentioning needle stick
injuries as a cause of transmission. It is to be remembered that all needle stick injuries occur
accidentally and are therefore preventable.
Therefore, the subject needs to be covered under the following headings:
1. HIV/AIDS statistics worldwide.

2. HIV/AIDS statistics for India
3. Methods of spread of the disease and related prevention strategy
4. Universal precaution in hospital settings
5. Needle Stick Injuries and their prevention
1. HIV/AIDS statistics worldwide, up to end of 2006

The latest statistics on the world epidemic of AIDS & HIV were published by UNAIDS/WHO in
November 2006, and refer to the end of 2006. These figures give the birds‘ eye view of the mangitude
of the problem.
Estimate Range
People living with HIV/AIDS in 2006 39.5 million 34.1-47.1 million
Adults living with HIV/AIDS in 2006 37.2 million 32.1-44.5 million
Women living with HIV/AIDS in 2006 17.7 million 15.1-20.9 million
Children living with HIV/AIDS in 2006 2.3 million 1.7-3.5 million
People newly infected with HIV in 2006 4.3 million 3.6-6.6 million
Adults newly infected with HIV in 2006 3.8 million 3.2-5.7 million
Children newly infected with HIV in 2006 0.53 million 0.41-0.66 million
AIDS deaths in 2006 2.9 million 2.5-3.5 million
Adult AIDS deaths in 2006 2.6 million 2.2-3.0 million
Child AIDS deaths in 2006 0.38 million 0.29-0.50 million
More than 25 million people have died of AIDS since 1981.

Africa has 12 million AIDS orphans.
At the end of 2006, women accounted for 48% of all adults living with HIV worldwide, and for 59% in
sub-Saharan Africa.
Young people (under 25 years old) account for half of all new HIV infections worldwide - around 6,000
become infected with HIV every day.
In developing and transitional countries, 7.1 million people are in immediate need of life-saving AIDS
drugs; of these, only 2.015 million (28%) are receiving the drugs.
234
Regional worldwide statistics for HIV & AIDS, end of 2006
Adults &
Adults & Adult
children Deaths of
Region children prevalence
living with adults & children
newly infected (15-49 years)
HIV/AIDS
Sub-Saharan Africa 24.7 million 2.8 million 5.9% 2.1 million
North Africa & Middle
460,000 68,000 0.2% 36,000
East
South and South-East
7.8 million* 860,000* 0.6%* 590,000*
Asia
East Asia 750,000 100,000 0.1% 43,000
Oceania 81,000 7,100 0.4% 4,000
Latin America 1.7 million 140,000 0.5% 65,000
Caribbean 250,000 27,000 1.2% 19,000
Eastern Europe & Central
1.7 million 270,000 0.9% 84,000
Asia
Western & Central
740,000 22,000 0.3% 12,000
Europe
North America 1.4 million 43,000 0.8% 18,000
Global Total 39.5 million 4.3 million 1.0% 2.9 million
* These numbers for South and South-East Asia are now thought to be too high, based on revised
Indian estimates published in July 2007. It is likely that the true number of people living with HIV in
this region is between 4 and 5 million.
During 2006 around four million adults and children became infected with HIV (Human
Immunodeficiency Virus), the virus that causes AIDS. By the end of the year, an estimated 39.5
million people worldwide were living with HIV/AIDS. The year also saw around three million deaths
from AIDS, despite recent improvements in access to antiretroviral treatment.
Sub-Saharan Africa HIV/AIDS Figures
The number of people living with HIV has risen from around 8 million in 1990 to nearly 40 million
today, and is still growing. Around 63% of people living with HIV are in sub-Saharan Africa. The
figure below gives a graphic view of the prevalence of HIV/AIDS in Africa as compared to the rest of
the world.
( Prevalence of HIV/AIDS -- The rest of the world vs Sub-Saharan Africa, covering the period 1990 to
2005 -- Source : WHO)
235
2. HIV/AIDS Statistics for India
India has a population of one billion, around half of whom are adults in the sexually active age group.
The first AIDS case in India was detected in 1986; since then HIV infection has been reported in all
States and Union Territories.
The spread of HIV in India has been diverse, with much of India having a low rate of infection and the
epidemic being most extreme in the southern half of the country and in the far north-east. The highest
HIV prevalence rates are found in Maharashtra in the west; Andhra Pradesh and Karnataka in the
south; and Manipur and Nagaland in the north-east.1
As of August 2006, 90% of all nationally reported AIDS cases have been found in 10 of the 38 States
Union Territories. The greatest numbers were in Maharashtra and Gujarat in the west; Tamil Nadu,
Andhra Pradesh and Karnataka in the south; and Manipur and West Bengal in the north-east.2
In the southern States, the infections are mostly due to heterosexual contact, while infections are
mainly found amongst injecting drug users in Manipur and Nagaland.
Estimated number of people living with HIV/AIDS, 20063

People living with HIV/AIDS 2 million -3.1 million
Adult (15 years or above) HIV
0.36%
prevalence
Previously it was thought that around 5 million people were living with HIV in India - more than in any
other country. Better data, including the results of a national household survey, led to a major revision
of the prevalence estimate in July 2007.
Back-calculation suggests that HIV prevalence in India has changed little over recent years and may
have declined slightly in 2006.
AIDS data for India, end of August 20064

Gender Cumulative AIDS cases
Male 88,245
Female 36,750
Total 124,995
The statistics for AIDS cases are a poor guide to the severity of the epidemic, as in many situations a
patient will die without HIV having been diagnosed, and with the cause of death attributed to an
opportunistic infection, such as tuberculosis.
Transmission
Number of cases %
Categories
Sexual 106,669 85%
Mother-to-child 4,755 4%
Blood and blood
2,563 2%
products
Injecting drug users 2,930 2%
Others (not specified) 8,078 6%
Total 124,995 100%
HIV prevalence among different population groups in India

The average HIV prevalence among women attending antenatal clinics in India is 0.88%. Much higher
rates are found among people attending sexually transmitted disease clinics (5.66%), female sex
workers (8.44%), injecting drug users (10.16%) and men who have sex with men (8.74%).
Rates vary widely between regions, and exceed 20% among female sex workers in Maharashtra,
injecting drug users in Delhi and Manipur, and men who have sex with men in Delhi.
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3. Prevention of HIV transmission
HIV can be transmitted in three main ways:
 Sexual transmission
 Transmission through blood
 Mother-to-child transmission
To be successful, an HIV prevention programme must make use of all approaches known to be
effective, rather than just implementing one or a few select actions in isolation. The share of resources
allocated to each area should reflect the nature of the local epidemic - for example, if most infections
occur among men who have sex with men then this group should be the main target for prevention
efforts.
It is known that many people don‘t fit into only one ―risk category‖. For example, injecting drug users
need access to condoms and safer sex counselling as well as help to reduce the risk of transmission
through blood.
First three requirements for prevention of HIV transmission
1. Create Widespread Awareness of HIV: There are three key things that can be done to help
prevent all forms of HIV transmission. First among these is promoting widespread awareness of
HIV and how it can be spread. Media campaigns and education in schools are among the best
ways to do this.
2. Provide Counselling and Testing facilities: Another essential part of a prevention programme is
HIV counselling and testing. People living with HIV are less likely to transmit the virus to others if
they know they are infected and if they have received counselling about safer behaviour. In
particular, a pregnant woman who has HIV will not be able to benefit from interventions to protect
her child unless her infection is diagnosed. Those who discover they are uninfected can also
benefit, by receiving counselling on how to remain that way.
3. Provide (or make available) the antiretroviral treatment: The third key factor is providing
antiretroviral treatment. This treatment enables people living with HIV to enjoy longer, healthier
lives, and as such it acts as an incentive for HIV testing. It also brings HIV-positive people into
contact with health care workers who can deliver prevention messages and interventions. Studies
suggest that HIV-positive people may be less likely to engage in risky behaviour if they are
enrolled in treatment programmes. Nevertheless, it is also possible that widespread availability of
treatment may make some members of the wider population less fearful of HIV infection, and
hence less willing to take precautions.
Sexual transmission
What works?
Someone can eliminate or reduce their risk of becoming infected with HIV during sex by choosing to:
 Abstain from sex or delay first sex
 Be faithful to one partner – The Lakshman Rekha, or have fewer partners
 Condomise, which means using male or female condoms consistently and correctly
There are a number of effective ways to encourage people to adopt safer sexual behaviour, including
media campaigns, social marketing, peer education and small group counselling. Specific
programmes should target key groups such as young people, women, men who have sex with men,
injecting drug users and sex workers.
Comprehensive sex education for young people is an essential part of HIV prevention. Studies have
shown that comprehensive sex education is more effective at preventing sexually transmitted
infections than education that focuses solely on teaching abstinence until marriage.
Condoms, if used consistently and correctly, are highly effective at preventing HIV infection. There is
no evidence that promoting condoms leads to increased sexual activity among young people.
Therefore condoms should be made readily and consistently available to all those who need them.
237
Male Circumcision: There is now very strong evidence that male circumcision reduces the risk of
HIV transmission from woman to man by around 50%, which is enough to justify its promotion as an
HIV prevention measure in some high-prevalence areas. It is not known whether circumcision also
affects the likelihood of male-to-female or male-to-male sexual transmission; further research on this
issue is ongoing.12
Providing treatment for sexually transmitted infections, such as chlamydia and gonorrhoea, is
another significant intervention. This is because such infections, if left untreated, have been found to
facilitate HIV transmission during sex.
Council people living with HIV: One group that shouldn‘t be overlooked by HIV prevention
programmes is those who are already living with the virus. Regular counselling can help HIV positive
people to sustain safer sexual behaviour, and so avoid onward transmission.
What are the obstacles?
Very difficult o bring about change in sexual behaviour: It is usually not easy for people to sustain
changes in sexual behaviour. In particular, young people often have difficulty remaining abstinent, and
women in male-dominated societies are frequently unable to negotiate condom use, let alone
abstinence. Many couples are compelled to have unprotected sex in order to have children. Others
associate condoms with promiscuity or lack of trust.
Not possible to discuss sex openly in all societies: Some societies find it difficult to discuss sex
openly, and some authorities restrict what subjects can be discussed in the classroom, or in public
information campaigns, for moral or religious reasons. Particularly contentious issues include
premarital sex, condom use and homosexuality, the last of which is illegal or taboo in much of the
world. Marginalisation of groups at high risk - such as sex workers and men who have sex with men -
can be a major hindrance to HIV prevention efforts; authorities are often unwilling to allocate adequate
resources to programmes targeting these groups.
Safe male circumcision demands considerable medical resources and some cultures are
strongly opposed to the procedure.
Transmission through blood
What works?
People who share equipment to inject recreational drugs risk becoming infected with HIV from other
drug users. Methadone maintenance and other drug treatment programmes are effective ways to help
people eliminate this risk by giving up injected drugs altogether. However, there will always be some
injecting drug users who are unwilling or unable to end their habit, and these people should be
encouraged to minimise the risk of infection by not sharing equipment.
Needle exchange programmes have been shown to reduce the number of new HIV infections
without encouraging drug use. These programmes distribute clean needles and safely dispose of
used ones, and also offer related services such as referrals to drug treatment centres and HIV
counselling and testing. Needle exchanges are a necessary part of HIV prevention in any community
that contains injecting drug users.
Small Group Counselling: Also important for injecting drug users are community outreach, small
group counselling and other activities that encourage safer behaviour and access to available
prevention options.
Screening All Blood: Transfusion of infected blood or blood products is the most efficient of all ways
to transmit HIV. However, the chances of this happening can be greatly reduced by screening all
blood supplies for the virus, and by heat-treating blood products where possible. In addition, because
screening is not quite 100% accurate, it is sensible to place some restrictions on who is eligible to
donate, provided that these are justified by epidemiological evidence, and don‘t unnecessarily limit
supply or fuel prejudice.
Reducing the number of unnecessary transfusions also helps to minimise risk.
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The safety of medical procedures and other activities that involve contact with blood, such as
tattooing and circumcision, can be improved by routinely sterilising equipment. An even better option
is to dispose off equipment after each use, and this is highly recommended if at all possible.
Practice Universal Precautions: Health care workers themselves run a risk of HIV infection through
contact with infected blood. The most effective way for staff to limit this risk is to practise universal
precautions, which means acting as though every patient is potentially infected. Universal precautions
include washing hands and using protective barriers for direct contact with blood and other body
fluids.23

Some authorities still refuse to support needle exchanges: Despite the evidence that they do not
encourage drug use, some authorities still refuse to support needle exchanges and other programmes
to help injecting drug users. Restrictions on pharmacies selling syringes without prescriptions, and on
possession of drug paraphernalia, can also hamper HIV prevention programmes by making it harder
for drug users to avoid sharing equipment.
Lack of facilities for rigorously screening blood supplies: Many resource-poor countries lack
facilities for rigorously screening blood supplies. In addition a lot of countries have difficulty recruiting
enough donors, and so have to resort to importing blood or paying their citizens to donate, which is
not the best way to ensure safety.
Lack of financial resources : In much of the world the safety of medical procedures in general is
compromised by lack of resources, and this may put both patients and staff at greater risk of HIV
infection.
Mother-to-child transmission
What works?
HIV can be transmitted from a mother to her baby during pregnancy, labour and delivery, and later
through breastfeeding. The first step towards reducing the number of babies infected in this way is to
prevent HIV infection in women, and to prevent unwanted pregnancies.
There are a number of things that can be done to help a pregnant woman with HIV to avoid passing
her infection to her child.
A course of antiretroviral drugs given to the mother during pregnancy and labour as well as to her
newborn baby can greatly reduce the chances of the child becoming infected. Although the most
effective treatment involves a combination of drugs taken over a long period, even a single dose of
treatment can cut the transmission rate by half.
A Caesarean Section reduces the baby‘s exposure to its mother‘s body fluids. This procedure lowers
the risk of HIV transmission, but is likely to be recommended only if the mother has a high level of HIV
in her blood, and if the benefit to her baby outweighs the risk of the intervention.
Breast Feeding : Weighing risks against benefits is also critical when selecting the best feeding
option. The World Health Organisation advises mothers with HIV not to breastfeed whenever the use
of replacements is acceptable, feasible, affordable, sustainable and safe. However, if safe water is not
available then the risk of life-threatening conditions from replacement feeding may be greater than the
risk from breastfeeding. An HIV positive mother should be counselled on the risks and benefits of
different infant feeding options and should be helped to select the most suitable option for her
situation.

Lack of drugs and medical facilities: In much of the world a lack of drugs and medical facilities
limits what can be done to prevent mother-to-child transmission of HIV. Antiretroviral drugs are not
widely available in many resource-poor countries, caesarean section is often impractical, and many
women lack the resources needed to avoid breastfeeding their babies.
HIV-related stigma: is another obstacle to preventing mother-to-child transmission. Some women are
afraid to attend clinics that distribute antiretroviral drugs, or to feed their babies on formula, in case by
doing so they reveal their HIV status.
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Policy measures
Strong Political Support: To be successful, a comprehensive HIV prevention programme needs
strong political leadership. This means politicians and leaders in all sectors must speak out openly
about AIDS and not shy away from difficult issues like sex, sexuality and drug use.
All sectors of the population should be actively involved . An effective response also requires
strategic planning based on good quality science and surveillance, as well as consideration of local
society and culture. All sectors of the population should be actively involved in the response, including
employers, religious groups, non-governmental organisations and HIV-positive people. Many of the
world's most successful HIV prevention efforts have been led by the affected communities
themselves.
Protecting and promoting human rights at all times and under all circumstances: HIV
epidemics thrive on stigma and discrimination related to people living with the virus and to
marginalised groups such as sex workers. Their spread is also fuelled by gender inequality, which
restricts what women can do to protect themselves from infection. Protecting and promoting human
rights should be an essential part of any comprehensive HIV prevention strategy. This includes
legislating against the many forms of stigma and discrimination that increase vulnerability.
4. Universal Work Precautions in clinical settings

According to WHO, Universal Work Precautions are simple infection control measures that reduce the
risk of transmission of blood borne pathogens through exposure to blood or body fluids among
patients and health care workers. Under the ―universal precautions‖ principle, blood and body fluids
from all persons should be considered as infected with HIV, regardless of the known or supposed
status of the person. Improving the safety of injections is an important component of universal
precautions.
These include simple common sense precautions like washing of hands and the use of barrier
precautions to prevent coming in contact with blood or body fluids, which may be potentially
contaminated with HIV.
Hand Washing
Hands should be promptly and thoroughly as soon as possible after contact with blood or other
potentially infectious body fluid and equipment or articles contaminated by them. Hand washing must
be done before putting on the gloves and immediately after taking off the gloves. Hand washing after
taking off the gloves is necessary because gloves may have inconspicuous holes and microbial
growth may occur due to the moisture inside gloves.
Means of Barrier Protection
These include
A : Wearing of gloves
B : Wearing of cap and mask
C : Eye protection
D : Water proof apron to protect the body
E : Adequately protective foot wear
A : Wearing of Gloves
Gloves should be worn to provide a protective barrier to prevent gross contamination of the hands
when handling blood or other potentially infectious body fluids, mucous membranes, non-intact skin,
and contaminated items. Wear gloves whenever you can reasonably anticipate contact with blood or
other potentially infectious materials, and contaminated items, or when handling or touching
contaminated items or surfaces.
Gloves should be worn particularly during the performance of the following day to day procedures:
240
1. putting an IV drip
2. giving an IV injection
3. doing the dressing of a wound
4. draining an abscess however small
5. stitching a laceration
6. removing stitches
7. doing any procedures in minor or major operation theatre
Gloves do not need to be worn in the following situations
1. examination of a patient with intact skin

2. giving an intra-muscular injection
Disposable (single-use) gloves should never be washed and reused. Remove gloves immediately
after use, before touching non-contaminated items such as door handles, telephones, computers,
equipment etc.
Wash hands thoroughly immediately after removal of gloves to avoid transfer of micro-organisms
to other environments. Wearing gloves does not replace the need for hand washing, because gloves
may have small, in-apparent defects or may be torn during use, and hands can become contaminated
during removal of gloves.
B : Wearing of Cap and Mask
Cap and mask must be worn
1. when entering an operation theatre – minor or major

2. performing a minor surgical procedure
3. performing a major surgical procedure
4. during wound dressings in the ward
5. performing all dental procedures
6. during delivery of a baby or any other obstetrical procedure
C : Eye Protection
Means of eye-protection such as plastic glasses with solid side shields, goggles, masks with clear
visors, and chin-length face shields, should be worn whenever splashes, spray, spatter, or droplets of
blood or other potentially infectious materials may be generated toward the eyes, nose, or mouth. In
these situations, wear either: (1) mask and eye protection or (2) a chin-length face shield. Personal
eyewear or wearing of plane glasses is not adequate as a barrier unless side panels are present.
D : Water proof apron to protect the body
Water proof apron must be worn whenever performing a surgical procedure. It is a common
experience during major surgical procedures to find the blood or body fluids flowing off the sides of
the body of the patient. This happens particularly during major or prolonged abdominal procedures.
Blood soaked fluids thus come in contact with the trunk of the surgeon and his assistant. If the
surgeon is not wearing a plastic apron to protect himself, blood then comes in contact with surgeon‘s
body. It is a common experience with all surgeons to find the OT dress and their own underclothes
soaked in blood after a major surgical procedure if they are not wearing a protective plastic apron.
It is also absolutely required to wear plastic apron while receiving casualties in the casualty
department. Road traffic accident patients often have multiple injuries and blood may be flowing off
the body when the patients are brought in. The casualty doctors therefore must be adequately
protected by wearing a plastic apron, adequately protective foot wear and must use gloves before
handing such patients.
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E : Adequately protective foot wear
It is commonly seen that the residents wear chappals while on duty in operation theatre or casualty
department. This is a disastrous situation which requires rectification. Feet of HCWs are as prone to
being exposed to potentially contaminated blood or body fluids from a patient as are their hands or the
trunk. Patients are often brought into the casualty after road accidents or other reasons of injury. Their
blood or body fluids can spatter the floor as they lie on the stretchers.
Adequate footwear should be the wearing of complete canvas shoes or the gum boots. Gumboots are
particularly required while performing endo-urological procedures. Here we always have the blood
contaminated irrigation fluids falling onto the floor where the urologist is standing to perform the
procedure. Trans Urethral Resection of prostate or a bladder tumour is one of the commonly
performed procedures and the returning irrigation fluid always contains blood. The feet of the surgeon
are therefore exposed to acquire a blood borne virus if there is the slightest breach of the skin of the
surgeon.
5. Needle Stick Injuries and their prevention

According to a recent document of National Health Service of UK, accidental exposure to serious and
potentially fatal Blood Borne Viruses including HIV, Hepatitis C and Hepatitis B is a significant
occupational health risk to health care workers. Needle stick and sharps injuries are the commonest
way in which healthcare workers are exposed to these viruses through their work. The risk of
acquiring infection through needle stick injury varies according to the nature of the injury, the nature of
the device and that of the blood borne virus.
It is a well-documented fact that all health care workers are at risk from needle stick injuries. The risk
of transmission of blood borne viruses is greater from patient to HCW than the other way round.
Health care workers need to be aware that not all patients have had potential infections diagnosed
and as such all blood, bodily fluids and tissue should be regarded as potentially infectious.
According to a recent US report, more than 600,000 to one million needle stick injuries to health care
workers occur every year.
American Fact Sheet on Needle Stick Injuries
1. Health care workers (HCWs) suffer between 600,000 and one million injuries from
conventional needles and sharps annually. These exposures can lead to hepatitis B,
hepatitis C and Human Immunodeficiency Virus (HIV) which leads on to AIDS.
2. At least 1,000 HCWs are estimated to contract serious infections annually from needle stick
and sharps injuries.
3. Registered nurses working at the bedside sustain an overwhelming majority of these

exposures.
4. Needle stick injuries are preventable. Over 80% of needle stick injuries could be prevented
with the use of safer needle devices.
5. More than 20 other infections can be transmitted through needle sticks, including:
tuberculosis, syphilis, malaria and herpes.
Transmission Rates following Needle Stick Injury

HBV : Transmission rate: 2-40%
HCV : Transmission rate: 2.7-10%
HIV : Transmission rate: 0.2-0.4%
It is obvious that the transmission rate is lowest with HIV and several times higher with Hepatitis B
Virus.
Prevention of Needle Stick Injuries

It is universally agreed that majority of needle stick injuries are preventable. Using safer needles can
prevent more than 80% of needle stick injuries. In India, use of blunt tipped needle is easiest to
242
achieve. These needles are now easily available and are cost effective. However, advances in needle
designs have made it possible to eliminate sharps from many uses-such as iv piggybacks, use of
blunt needles or retract the needle so it's no longer a danger.
Placing sharps containers within reach and at eye level in operation theatres and by the bed side in
every patient room reduces the risk of injury. Disposable knife blades and needles can easily be
disposed right away after use thereby preventing the need to be handled by more than one HCW.
Operation Theatre precautions to prevent needle stick injuries

There are several measures that should to be taken to avoid actual injury in the operation theatre and
these should be considered seriously:
 no more than one person should work in an open wound/cavity (unless essential). It is often
seen that besides the surgeon‘s hand, there are also the hands of one or two assistants in the
abdominal wound. This crams the space and if suturing is being done at depth, there is a
greater chance of sustaining a needle stick injury.
 use the ‗hands-off‘ technique: the needle is not handled by more than one person ,i.e., the
surgeon. The assistants must be in hands-off position so that they do not come in contact with
the needle at all.
 hand-to-hand passing of needles during operations must be avoided.
 announce to your colleague or the nurse assisting you that the needle is being returned in the
needle holder.
 ensure needles and sharps are not left exposed, these must be placed in a kidney tray and
not handed back hand to hand during a surgical procedure.
 use instruments rather than fingers for retracting the wound and suturing. In spite of
repeatedly highlighting this point, it is still observed that residents frequently use hands to
retract a wound for the sake of expediency.
 use instruments when handling needles. It is accepted universally that the needle should only
be held only with a needle holder. A change in the position of the needle should also be
effected only with the use of instruments like toothed forceps.
 direct needles and instruments away from your own, or assistant‘s hand.
 donot bend or snap used needles. This process may lead to needle stick injury.
 Never re-cap a used needle. This may lead to accidental needle stick injury if the cap is
missed while capping the needle.
 Place used needles into a clearly labelled and puncture-proof sharps approved container.
Never use a hand held curved needle for suturing skin. It is a practice with some institutions to
provide large hand held needles for suturing wounds, especially after a cut down procedure to
access a vein.
Post Exposure Prophylaxis ( PEP )

as a preventive measure after needle stick injury
Research evidence seems to suggest that the use of anti-HIV drugs like zidovudine in combination
with other anti-HIV drugs if given soon after an injury can reduce the rate of transmission. Such
treatment is referred to as Post Exposure Prophylaxis (PEP). PEP is recommended for health care
workers if they have had a significant occupational exposure to blood or another high risk body fluid
which is likely to be infected with HIV. It is recommended that PEP should be commenced as soon as
possible after exposure and ideally within the hour.
Although exposure through needle stick injuries can usually be avoided by following good working
practices, health care workers should consider the implications of taking PEP. This will help them to
make a swift decision in the event of an accident where an injury occurs. In the UK, the Department of
Health guidelines for PEP are that most needle stick injuries should be treated with a triple
combination of antiretroviral drugs for four weeks. Recommended drugs are zidovudine, lamivudine
and nelfinavir. NACO has made similar recommendation for India.
243
References
1. HIV/AIDS epidemiological Surveillance & Estimation report for the year 2005, NACO, April 2006
2. Monthly updates on AIDS, NACO, 31 August 2006
3. 2.5 million people living in India with HIV, according to new estimates, UNAIDS/NACO/WHO, 6 July 2007
4. Monthly updates on AIDS, NACO, 31 August 2006
5. HIV/AIDS epidemiological Surveillance & Estimation report for the year 2005, NACO, April 2006
6. www.AVERT.org -- British based intrnational charity website on Averting HIV and AIDS. Author gratefully
acknowlwdges the use of some information from this website.
7. Universal Precautions and Needle Stick Injuries: V J Anand in Surgery Update 2006: Proceedings of the XXIII
National Continuing Medical Education Program in Surgery ( Department of Surgery, Maulana Azad Medical
College, New Delhi) – pages 180-185, September 2006.
244
Antiretroviral therapy for HIV infection
Dr. M.K.Daga
TREATMENT OF HIV INFECTION
The HIV/AIDS is now 25 year old and in these 25 years, more than 60 million people have been
infected by human immunodeficiency virus (HIV)
The treatment of patients with HIV infection requires not only a comprehensive knowledge of the
possible disease processes that may occur but also the ability to deal with the problems of a chronic
potentially life threatening illness. The appropriate use of potent combination antiretroviral therapy
and other treatment and prophylactic interventions is of critical importance in providing each patient
with the best opportunity to live a long and healthy life despite the presence of HIV infection. In
addition to medical interventions, the health care provider has a responsibility to provide each patient
with appropriate counseling and education concerning their disease as part of a comprehensive care
plan. As with other disease, therapeutic decisions should be made in consultation with patient, when
possible and with the patients attendant if the patient is incapable of making decisions.
Once the diagnosis of HIV infection has been made, the extent of disease can be determined by
laboratory studies and other examinations. Subsequently short term and long term medical
management strategies should be developed based upon most recent information available.
Combination antiretroviral therapy or HAART is the cornerstone of management of patients with HIV
infection. Suppression of HIV replication is an important component in prolonging life as well as
improving the quality of life in patients with HIV infection. These drugs cannot eradicate the HIV
infection from body because a pool of latently infected CD 4 cells is established during the earliest
stages of HIV infection and persists life long.
The primary goal of anti retroviral therapy are maximal and durable reduction in plasma viral levels
and restoration of immunological function aimed at improvement in quality of life and prolongation of
life as well.
BASIC PRINCIPLES OF ANTIRETROVIRAL THERAPY
A continuous high level of replication of HIV takes place in the body right from the early stages of
infection. At least 1010 viral particles are produced and destroyed each day. The HIV destroys CD4
cells, while body produces more CD4 cells. This balance is maintained for some years after which the
rate of CD4 destruction becomes more than that of CD4 production. This progressive immune system
damage results in susceptibility to different opportunistic infections (OI), malignancies, neurological
diseases, wasting and, ultimately death.
The most effective way to achieve and maintain durable suppression of HIV replication is the
simultaneous initiation of a combination of at least three drugs from different classes of ARV drugs.
Some important factors that must be kept in mind while staring ART are:
1. To assess the severity of disease according to the baseline CD4 cell count and viral load, if
possible.
2. The patients ‗willingness‘ and ‗readiness‘ to begin therapy.
3. The patients‘ education regarding pill burden, dosing frequency, food and fluid consideration,
adverse effects, adherence issues and drug interactions;
4. Co-morbid conditions such as tuberculosis, liver disease, depression or mental illness,
cardiovascular disease, drug dependency, pregnancy, and family planning status.
WHEN TO START TREATMENT
The ‗early‘ therapy has advantages in terms of easy achievement of viral control, lower risk of
resistance with optimal viral suppression and decreased risk of HIV transmission. The ‗delayed
therapy‘ avoids negative effect on quality of life of an asymptomatic individual, preserves future drug
option, but may be associated with difficulty in suppressing viral replication and irreversible immune
245
system depletion. The recommendations on starting treatment are based on symptoms, CD4 cells
counts, and viral load, if possible.
Various guidelines have been issued from time to time by different expert groups constituted by
Department of Health and Human Services (DHHS), USA; International AIDS Society, British HIV
Association (BHIVA), Association of Physicians of India etc. The recommendation of starting ART as
per guidelines released by Department of Health and Human Services (DHHS), USA in October 2006
recommend that.
 Antiretroviral therapy (ART) should be given to all patients with history of AIDS defining illness
or severe symptoms of HIV infection regardless of CD4 cell count,
 ART is also recommended for asymptomatic patient with CD4 count <200 cells/cmm.
 Asymptomatic patient with CD4 count of 200-350 cells /cmm should be offered treatment.
 For asymptomatic patient with CD4 count > 350 cells / cmm and plasma viral load > 100,000
copes / ml, the most experienced clinicians defer therapy, but some may consider initiating
treatment.
 Therapy should be deferred for patients with CD4 cells >350 cells / cmm and plasma HIV
RNA <100,000 copies / ml
These guidelines are summarized at Table 1.
Table 1 : Indications for initiating antiretroviral therapy for the chronically HIV – I infected patients
(DHHS Guidelines) – October 2006
Clinical Category CD4 cell count Plasma HIV RNA Recommendation
AIDS-defining illness Any value Any value Treat

or severe symptoms*
Asymptomatic CD4 cells < 200/mm3 Any value Treat
Treatment should be offered

CD4 cells > 200/mm3
Asymptomatic Any value following full discussion of pros
but < 350/mm3
and cons with each patient
Most clinicians recommend
Asymptomatic CD4 cells > 350/mm3 > 100,000 deferring therapy, but some
clinicians will treat
Asymptomatic CD4 cells >350/mm3 <100,000 Defer therapy
 AIDS-defining illness per Centers for Disease Control, 1993. Severe symptoms include
unexplained fever or diarrhea > 2-4 weeks, oral candidiasis, or > 10% unexplained weight loss.
WHO has also issued guidelines for initiating ART in resource limited settings. These guidelines are
divided into two categories depending on whether CD4 count facilities are available or not. The
threshold for initiating therapy is CD4 count <200 cells / mm or clinical stage IV. The WHO
recommendations are summarized in Table 2.
Table 2: When to start antiretroviral therapy-WHO guidelines
WHO Clinical Staging CD4 Testing not available CD4 Testing Available
1
Do not treat [A-III]
Treat if CD4 count is below 200
Do not treatb [B-III]
2 cells/mm3a [A – III]
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Consider treatment if CD4 count is below
3 Treat [A-III] 350 cells /mm3acd and initiate ART before
CD4 count drops below 200 cells/mm3e
[B-III]
Treat irrespective of CD4 cell counta [A-
4 Treat [A-III]
III]
a CD4 cell count advisable to assist with determining need for immediate therapy for situations
such as pulmonary TB and severe bacterial infections, which may occur at any CD4 level.
b A total lymphocyte count of 1200//mm3 or less can be substituted for the CD4 count when the
latter is unavailable and mild HIV disease exists it is not useful in asymptomatic patients.
Thus, in the absence of CD4 cell counts and TLCs, patients with WHO adult clinical stage 2
should not be treated.
c The initiation of ART is recommended in all HIV-infected pregnant women with WHO clinical
stage 3 disease and CD4 counts below 350 cells//mm3
d the initiation of ART is recommended for all HIV-infected patients with CD4 count below 350
cells/mm3 and pulmonary TB or severe bacterial infection.
e The precise CD4 cell level above 200/mm3 at which ARV treatment should be started has not
been established.
WHAT TO START WITH?
The antiretroviral drugs act on various stages of life cycle of HIV in the body and work by interrupting
the process of viral replication. Theoretically, these drugs can act at following steps in viral
replication:
i. block binding of HIV to target cell (Fusion Inhibitors),

ii. block the viral RNA cleavage and one that inhibits reverse transcriptase (Reverse
Transcriptase Inhibitors),
iii. block the enzyme integrase, which helps in the proviral DNA being incorporated into the
host cell chromosome (Integrase Inhibitors)
iv. block the RNA to prevent viral protein production,
v. block enzyme protease (Protease Inhibitors),
vi. inhibit the budding of virus from host cells.
Currently available agents target the virus mainly by inhibiting the enzyme reverse transcriptase
inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors
(PIs) and preventing fusion of virus with CD4 cells (Fusion Inhibitors).( Table-3)
To date, most clinical experience on use of combination therapy (Highly active antiretroviral therapy,
HAART) in treatment-naive individuals has been based on three different types of combination
regimens, namely : NNRTI – based (2 NRTI + NNRTI), PI – based (2 NRTI + 1 or 2 PI) and triple
NRTI – based regimens.
Table 3 : Classes of drugs available

Nucleoside reverse Non-nucleoside reverse
transcriptase inhibitors transcriptase inhibitors Protease inhibitors (PI)
(NRTI) (NNRTI)
Zidovudine (AZT)/ZDV* Nevirapine* (NVP) Saquinavir* (SQV)
Stavudine (d4T)* Ritonavir* (RTV)
Lamivudine (3TC) Efavirenz* (EFV) Nelfinavir* (NFV)
Didanosine (ddl)* Delavirdine (DLV) Amprenavir (APV)
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Zalcitabine (ddC)* Indinavir* (INV)
Abacavir * (ABC) Fusion Inhibitors (FI) Lopinavir / Ritonavir (LPV)*
Emtricitabine (FTC) Enfuviritide (T-20) Foseamprenavir (FPV)
(NtRTI) Atazanavir (ATV)*
Tenofavir (TDF)* Tipranavir (TPV)
* Available in India
The therapy has to be individualized on a case to case basis taking into consideration various factors
like tolerability, adverse effect profile, convenience, likelihood of adherence, affordability, concomitant
drug use (e.g. rifampicin), mental illness, cardiac status and other co-existing illness etc.
The present recommendation is to initiate therapy with an NNRTI based regimen (first line therapy).
The efficacy of NNRTI based regimen has been shown to be equivalent to PI based regimen in a
number of trials like Atlantic study, Combine study, Dupont study and Focus trial. NNRTI based
regimen is associated with fewer toxicities and spare PIs for future use (second line therapy). But,
NNRTIs have a low genetic barrier for resistance, and even a single mutation can confer cross
resistance across the entire class.
Nevirapine is NNRTI backbone for most of first line regimens except for patients with TB co-infection,
background liver disease and hepatitis B and C co-infection. A 14 day lead in dose of NVP of 200 mg
once daily should be given to all patients before increasing to full dose of 200 mg twice a day as NVP
may be associated with severe hypersensitivity skin reaction in some cases.
Efavirenz is the only NNRTI which can be used concomitantly with rifampicin making it a very valuable
drug for HIV-TB co-infection. However, it should be used in caution in women of child-bearing age
(not on adequate contraception) and those with existing depression and mental illness. The CNS
disturbances associated with EFV are usually self-limiting and disappear in 2-4 weeks.
FOLLOW-UP OF PATIENTS ON ART
The broad guidelines on follow-up on patients on ART are depicted in Table 4.
Table 4: Follow-up of patients on ART

Every 6 Months
1 Month 3 Months 6 Months
thereafter
Clinical*
Yes Yes Yes Yes
(monthly)
CD4 counts No No Yes Yes
LFT‘s Yes No Yes Yes
CBC Yes (AZT) No Yes Yes
Other chemistry As Clinically indicated
DRUG INTERACTIONS
Potential drug-drug interaction should be taken into consideration while selecting an antiretroviral
regimen and review of drug interaction potential should be undertaken when any new drug is to be
248
added to an existing antiretroviral combination. A list of significant drug interactions with different
antiretroviral agents should be available at ART clinic for ready reference.
The list of drugs that may have significant interactions with PIs and / or NNRTIs is extensive and
continuously expanding. Some examples of these drugs include medication that are commonly
prescribed for HIV patients such as lipid-lowering agents (the ―statins‖), benzodiazepines, calcium
channel blockers, immunosuppressants (such as cyclosporine, and tacrolimus), neuroleptics,
sildenafil, ergotamine, rifamycins, azole, antifungals, macrolides, oral contraceptive and methadone.
CHANGING THERAPY
The reasons for changing an ART regimen include adverse effects, inconvenient regimens such as
dosing / number of pills that may compromise adherence, occurrence of active tuberculosis and
pregnancy and treatment failure.
The decision to change regimen should be based on clinical history, physical examination, routine and
relevant laboratory investigations, CD4 counts and changes in count. An assessment of adherence to
medications should be made and remaining treatment options considered. Potential of initial viral
resistance, drug interaction and diet also need to be considered (table 5).
a. Change due to Adverse Effects / Intolerance

b. Chang due to Treatment Failure
Table 5: Recommended second-line regimens in adults and adolescents
Second-line regimens for treatment failure Alternative second-line

First line regimens
regimen for treatment failure
ZDV/3TC plus NVP or EFZ RTV-enhanced PI + d4T/ddl -RTV-enhanced PI + ABC/ddl
ZDV/3TC/ABC NNRTI + LPV/r + /- d4T/ddl RTV-enhanced PI + d4T/ddl
ZDV/3TC/RTV-enhanced PI or
NNRTI + d4T/ddl NNRTI + ABC/ddl
NFV
ANTIRETROVIRAL THERAPY IN SPECIAL SITUATIONS
Some of the situations that demand special consideration include adolescents, women, pregnancy,
breastfeeding mother, those with hepatitis B and C and tuberculosis co-infection. Of all these, special
mention has to be made of tuberculosis, as it is commonest opportunistic infections in HIV-infected
people in South East Asia.
The management of HIV and TB co-infection is complicated because some antiretroviral agents
produce unacceptable drug interactions with anti-tubercular agents and / or can increase toxicity of TB
treatment. Tuberculosis treatment following the DOTS strategy should be initiated promptly in
diagnosed cases of TB. The standard four drug regimen for six months is advocated for all except for
those with CNS involvement or those with slow response. These group of patients should be treated
for nine months to one year.
The two major issues in the clinical management of patients with HIV and TB are when to start ART
and which regimen to use. Initiation of ART for TB patients at high risk for HIV disease progression
and mortality is recommended, i.e. a CD4 count <200 cells/mm3, or extrapulmonary TB. For patients
who develop TB with CD4 counts in the 50-200 cells/mm3 range or, in the absence of CD4 testing,
have total lymphocyte counts <1200 cells / mm3, ART should be started after the first two months of
TB therapy, because the toxicity of TB treatment is greatest during this period. In the subset of
patients with very low CD4 cell counts (<50 cells/mm3) or those with other severe HIV disease, ART
should be started as soon as TB therapy is tolerated. These group of patients should be specially
monitored for development of IRIS).
249
Patient already receiving ART when they develop TB should adjust the regimen to be compatible with
TB treatment (EFV based). Following completion of antitubercular therapy, the ART regimen can be
continued or changed depending upon the clinical and immunologic status of the patient and
affordability or drugs (EFV being more expensive than NVP)
SURGICAL ISSUES:
HIV infected patients present to the surgeon with three notable clinical problems: immunosuppression,
renal failure and cardiac dysfunction. One should be aware of immune status of HIV infected patient.
The risk of infection after a surgical procedure with normal CD4+ counts is similar to non HIV patient.
But with CD4+ count less than 200, risk is higher, though it is from opportunistic organisms.
Renal failure in these patients can be the result of specific HIV related nephropathy, which occurs in
up to 10% of this population. Another possible cause is drug toxicity from antiretroviral and
antimicrobial medications. Cardiac disease in HIV patients is acquired one and has become more
apparent due to longer survival of these patients. In addition, malignancy has been increasingly
recognized over last 2 decades as a consequence of HIV infection. Initially B cell lymphoma and
Kaposi sarcoma was thought to be related to the immunosuppression of the host. Other tumors have
now been associated with HIV infection, including sqnamous cell cancers of the cervix and anus and
lung cancer.
Splenectomy, venous access devices; gastro intestinal diseases causing acute cholecysitis and acute
cholangitis requiring emergency surgical interventions need to be taken care of. Acute perforations of
GI tract from CMV infection cryptosporidiosis and candidiasis as well as from necrotic lymphoma have
also been reported.
One study of AIDS patient requiring a laparotormy – identified four distinct clinical syndrome which
called for surgical intervention.
a) Peritonitis secondary to CMV enterocolitis and perforation

b) Non-Hodgkin lymphoma of GI tract presenting as obstruction
c) Kaposi sarcoma of GI tract
d) Mycobacteria infection of the retroperitoneum or the spleen
HIV AND HEALTH CARE WORKER
Health car workers have a small but definite risk of becoming infected with HIV due to professional
activities. Taking together the data from several large studies suggest that the risk of HIV infection
following a percutaneous exposure to HIV contaminated blood is 0.3% and after a mucous membrane
exposure, approximately 0.09%. Some episodes of HIV transmission after non-intact skin exposure
have been documented, the average risk for transmission by this route has not been precisely
quantified. The risk after exposure to other body fluids is also less than exposure to blood. This risk of
infection with a suture needle is considerably less than that with a blood drawing needle. Most cases
of health care worker seroconversion occur due to needle stick injuries.
POST EXPOSURE PROPHYLAXIS
Factors associated with increased risk for occupational transmission of HIV infection:
 Deep injury
 Presence of visible blood on instrument
 Injury with a device placed in vein or artery
 Terminal illness
 Lack of post exposure antiretroviral therapy
 Pregnancy in health care worker
 Exposure to drug resistant virus
250
Type of Exposure and Relative Risk
Type of Exposure Relative Risk
Deep needlestick injury or cut 16:1
Fresh blood on the penetrating instrument 5:1
Penetrating needle previously placed in blood vessel 5:1
Source person with high viral load 6:1
Exposition of mucosal membrane 1:10
Exposition of inflammatory damaged skin 1:10
Choice to agents is largely empirical and also depends upon :

a) risk assessment of injury & HIV status clinical condition and viral load
b) solid bore v/s hollow bore needle
c) source needle used for arterial or venous puncture
d) whether the injury involved intact or non-intact skin
 Clean the wound and apply antiseptic
 A combination of two nucleoside analogue reverse transcriptase inhibitors to be given for 4
weeks for routine exposure namely zidovdine and lamivudine
 A combination of two nucleoside analogue reverse transcriptase inhibitors plus a third drug
(protease inhibitor) given for 4 weeks for high risk or complicated exposure (Zidovudine +
Lamivudine + Indanavir or Nelfinavir)
Recommended antiviral prophylaxis in HIV Postexposure Prophylaxis

NRTI PI / NNRTI
AZT + 3TC Nelfinavir (2 x 1,250 mg)
1. AZT + 3TC (2 x 300/ 150 mg) or
Lopinavir (2 x 400 / 100 mg)
or or
2. AZT (2 x 250 mg) plus 3TC (2 x 150 or Indinavir (3 x 800 mg)
1 x 300 mg) or
Efavirenz (1 x 600 mg)
Recommended treatment for opportunistic infections in HIV

CD4 Count and Opportunistic Infection
251
CMV Retinitis
Pneumocystis pneumonia
252
Cerebral Toxoplasmosis
Atypical Mycobacteriosis
253
Herpes simplex infection
Herpes zoster infection
Progressive multifocal leukoencephalopathy
Cryptosporidiosis
254
Cryptococcosis
Candidiasis
Salmonella septicemia
255
Bacterial Pneumonias
POST EXPOSURE PROPHYLAXIS
Risks associated with various type of exposure
256
Recommendations for Post exposure prophylaxis
PEP – Recommended antiretroviral combination
With improvement in therapy patients are living longer after the diagnosis of AIDs maintaining access
to quality care and treatment is one key element. Another key element is sustaining lower mortality is
developing new treatment for patients who have been heavily treated with existing agents. For
patients whose disease progresses even though they are receiving appropriate treatment, meticulous
palliative care must be provided. With attention to pain control, spiritual needs, and family (biologic
and chosen) dynamics).
257
258
Counseling and voluntary testing for HIV/AIDS
Dr. Suneela Garg, Anita Nath
What is HIV Counseling?
Counseling in the context of HIV is important in the provision of prevention, treatment and care
services. HIV/AIDS counseling/education is a confidential dialogue between a client and a counselor
aimed at providing information on HIV/AIDS and bringing about behaviour change in the client. It is
also aimed at enabling the client to take a decision regarding HIV testing and to understand the
implications of the test results.
HIV counseling includes :
1. HIV pre-test counseling/information: This involves provision of basic information on

HIV/AIDS and risk assessment to direct walk-in clients.
2. HIV post-test counseling: Here the client is helped to understand and cope with the
HIV test result:
In case of a negative test result, the counselor reiterates basic information on HIV and assists the
client to adopt behavior that reduces the risk of getting infected with HIV in the future. In case the
client is in the window period, a repeat test is recommended. Those clients with suspected
tuberculosis are referred to the nearest microscopy centre. In case of a positive test result, the
counselor assists the client to understand the implications of the positive test result and helps in
coping with the test result. The counselor also ensures access to treatment and care, and supports
disclosure of the HIV
status to the spouse.
What is an Integrated Counseling and Testing Centre?

An integrated counseling and testing centre (previously known as Voluntary Counseling and Testing
Centre) is a place where a person is counseled and tested for HIV, on his own free will or as advised
by a medical provider. The main functions of an ICTC include:
*Presenting Author : Professor and Head of Faculty of Medical Sciences, Community Medicine,
MAMC, New Delhi
** Department of Community Medicine, MAMC, New Delhi
 Early detection of HIV.

 Provision of basic information on modes of transmission and prevention of HIV/AIDS for
promoting behavioral change and reducing vulnerability.
 Link people with other HIV prevention, care and treatment services.
Where can an ICTC be located?
An ICTC may be located in
1. Health facilities owned by the government : These include

 Medical college,
 district hospital,
 sub district hospital,
 community health centre (CHC) or a 24-hour primary health centre (PHC)
which caters to a population of 30,000–40,000, having a minimum of 30
beds, at least 50 deliveries per month and a TB microscopy centre.
2. In the private/not-for-profit sector : These include

 Maternity homes/hospitals with >50 deliveries in a month in ―A‖ and ―B‖ category
districts and >100 deliveries in a month in ―C‖ and ―D‖ category districts;
 Hospitals/clinics which treat >100 TB patients in a month;
259
 Hospitals/clinics which have a case load of >100 sexually transmitted infections
(STIs) in a month;
 Diagnostic laboratories which perform >150 diagnostic HIV tests in a month;
 Industrial zones that employ a large number of people, particularly
migrants/casual labour on an informal/contractual basis
3. In public sector organizations/other government departments such as :

 Railway stations and bus terminals located at major junctions on trunk routes and
handle a large volume of passengers every day;
 Central prisons with a large number of inmates;
 Health facilities run by State/Central Police Organizations/Armed Forces;
 Health facilities run by public sector organizations catering to large volumes of
migrant workers;
 Health facilities run by public sector organizations which handle >100 deliveries in
a month or have a TB microscopy centre;
 Public sector organizations such as those in the mining industry which employ
large number of persons, particularly migrants/casual labour;
 University campuses
Settings in which Counseling may be offered :
There are two settings in which counseling and testing can be offered to clients :
1. Provider-initiated counseling and testing

There are three varieties of patients who are offered provider-initiated counseling and testing:
 Patients who present at a health facility with symptoms suggestive of HIV infection.
Examples include patients with pneumonia, TB or persistent diarrhoea.
 Patients attending the health facility with conditions that could be associated with HIV
such as STI/RTI.
 Settings with large client numbers such as pregnant women who register at ANCs.
These also include pregnant women who directly come in labour without any
antenatal check-up.
In such cases, the client is given:

 Basic information on HIV,
 Educated about testing for HIV,
 Provided the clinical and prevention benefits of testing
 Informed about the potential risks such as discrimination.
 The follow-up services that will be provided
The client is also informed about their right to refuse testing and that declining an HIV test will not
affect their access to services that do not depend upon knowledge of the HIV status.
2. Client-initiated counseling and testing or self-referred
These are clients who present themselves at the ICTC of their own free will. The motivation to visit
and avail of the ICTC services could be based on individual risk behavior or information and advice
received, for example, from a friend, sexual partner, or outreach worker/peer educator in an NGO, or
from advertisements in the mass media.
Here the client is counseled for HIV and then ―opts in‖ or actively agrees to be tested for HIV. Written
consent has to be obtained from such clients before testing. HIV testing is followed by regular post-
test counseling. Follow-up counseling is provided for those who are in the window period.
Voluntary Counseling as the gateway to HIV Prevention and Care
Voluntary Counseling and Testing can serve as an entry point for appropriate medical and supportive
care as depicted below :
VCT. Summary of evidence
. V (voluntary).encourages people to present at services they may otherwise avoid
260
. C (counseling).is more effective than simply providing health information
. T (testing).quality, same tests are cost-effective and increase uptake and demand for VCT
Beneficial disclosure and ethical partner notification
Although the epidemic is almost 20 years old in India and though HIV prevalence is high in many
communities, HIV/AIDS continues to be denied at many levels; to be highly stigmatized; and to cause
serious discrimination. The partner notification strategies proposed as an integral component of VCT
programmes are designed to assist in reducing the denial, stigma and discrimination associated with
the disease. In the context of HIV/AIDS, UNAIDS and WHO encourage beneficial disclosure of
HIV/AIDS status. This disclosure is
(i) voluntary;
(ii) respects the autonomy and dignity of the affected individuals;
(iii) maintains confidentiality as appropriate;
(iv) leads to beneficial results for the individual, their sexual and drug-injecting partners, and
family;
(v) leads to greater openness in the community about HIV/AIDS; and
(vi) meets ethical imperatives so as to maximize good for both the uninfected and the infected.
An HIV positive person should be encouraged through counseling and tools such as role play to share
the positive test result with their spouse, sexual or needles haring partner(s) and bring the spouse or
partner for counseling to a VCTC. This process of helping the client for sharing the test result might
take more than one visit. In case of difficulty, the counselor could contact positive network groups to
facilitate disclosure. As per a Supreme Court decision, if the HIV positive partner refuses to disclose
the HIV status to the spouse or partner it is the obligation of the treating physician or counselor to
disclose the result to the spouse/partner of the HIV positive person.
Requirements for successful VCT implementation

• Realistic training and support of counselors
• Social marketing and community mobilization
• Referral networks and support services
• Appropriate facilities—time, privacy, confidential information management, accessibility
• Effective and responsive monitoring and evaluation
Lessons learnt
• Mandatory testing can easily become common practice (e.g. in surgery or obstetric care), and
voluntary counseling mandatory.
• Anonymity and protection of confidentiality are critical for trust in and demand for VCT.
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• Integrating VCT services with comprehensive prevention, treatment and care programmes
such as management of family planning, STI, TB is essential.
Role of VCT in HIV prevention, care and support
• Supervision and monitoring are essential for quality services.

• Providing fast test results while maintaining test quality increases the effectiveness of VCT
services.
• Implementing HIV sensitization of all health-care staff increases acceptance of VCT.
• VCTs targeting specific groups are effective.
• PLHAs in VCT play an important role in reducing stigma and discrimination.
• Counseling sessions should not used as a data collection tool.
• Defined roles and responsibilities of counselors, laboratory technicians and health-care staff
improve the quality of VCT services.
• Standardization through forms, guidelines and procedures improves the quality of VCT.
Public health challenges

• Gender and sexual negotiation
—men control VCT decision-making
—men control sexual behaviour decisions
• Broaden VCT models
—men need to be engaged in VCT
—for vulnerable groups such as young people, (to be youth-friendly) and
—groups with high risk behaviour
• Uninterrupted supply of quality test kits
—new testing technologies (rapid tests)
• Quality of counseling
• Access to VCT and uptake of results
• Ethical, cost-effective models of counseling
—group information-giving
—targeting services to users
—provision of VCT outreach services
—telephone counseling for less mobile clients and those who live in areas with limited
services (rural areas)
• Scaling-up without diluting the quality of service
• Increasing access to care
• Targeting services to users
• Caring for carers
—professional supervision
—support
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Investigations for upper limb ischaemia
Dr. Anju Garg
Arterial disease is diagnosed much less commonly in the upper extremity than in the lower extremity.
Unusual pathologies such as vasculitis, entrapment syndromes and trauma make up a higher
proportion of cases of symptomatic arterial disease in the upper extremity.
Normal Anatomy
A basic knowledge of the normal arterial anatomy alongwith the key collateral pathways is essential in
localization and diagnosis of pathology.
The main artery of the upper limb is the subclavian artery. The right subclavian artery arises as a
branch of the brachiocephalic or innominate artery and the left arises directly from the arch of aorta. It
runs laterally posterior to the subclavian vein and anterior to the scalene muscle. At the outer edge of
the Ist rib it becomes known as the axillary artery. The branches of subclavian artery are:
- Vertebral artery
- Internal thoracic artery
- Thyroocervical trunk – inferior thyroid artery
- suprascapular artery
- superficial cervical artery
- Costocervical trunk – superior intercostal artery
- deep cervical artery
- Dorsal scapular artery.
The axillary artery runs behind the pectoralis major and minor muscles and continues as the brachial
artery at the outer edge of teres minor muscle. Its branches are:
– Superior thoracic artery

- Thoraco-acromial artery
- Lateral thoracic artery
- Subscapular artery
- Anterior and posterior humeral circumflex arteries.
The brachial artery lies in the upper arm alongwith the paired brachial veins, basilic vein and median
nerve. Its named branches are:
– Deep brachial artery

- Superior and inferior ulnar collateral arteries.
It divides into the radial and ulnar arteries at the level of the radial head.
The radial artery lies along the lateral aspect of the forearm and gives off the radial recurrent artery
along with muscular branches in the forearm.The ulnar artery which is larger than the radial artery
descends on the medial side of forearm and gives rise to the common interosseous artery and
ulnar recurrent branches.
In the hand, the superficial palmar arch is a direct continuation of the ulnar artery . It is completed
by the one of the branches of radial artery on the lateral aspect. Four digital arteries arise from the
convexity of the arch and pass to the fingers. The deep palmar arch is the direct continuation of the
radial artery and is completed on the medial side by the deep branch of ulnar artery .
The arch sends branches superiorly, which take part in anastomosis around the wrist joint, and
inferiorly,to join the digital braches of the superficial arch.
The arterial anatomy of the upper limb is extremely variable and deviations from the classic pattern
given above are commonly seen, specially in the hand.
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Collateral Circulation
With proximal subclavian artery obstruction, collateral blood flow from the contralateral
vertebrobasilar system may run into the ipsilateral mid-subclavian artery. With distal subclavian
artery obstruction, major collateral pathways are present across the thyroidal artery system,
between the internal thoracic and lateral thoracic arteries, and between the thyrocervical trunk and
circumflex humeral arteries. With axillary artery obstruction, a rich network of muscular branches
around the shoulder girdle provides collateral blood supply into the brachial artery.
With proximal brachial artery obstruction, the subscapular and posterior humeral circumflex
arteries provide flow through muscular branches into the distal brachial or forearm arteries. In cases
of mid-brachial artery occlusion, the deep brachial artery and superior ulnar collateral arteries
supply the radial recurrent and ulnar recurrent arteries, respectively, above the elbow. The radial and
ulnar recurrent arteries are the chief pathways across the elbow in patients with distal brachial artery
occlusions.
When the radial or ulnar artery is obstructed, the opposing forearm artery, along with the anterior
interosseous or median artery (if persistent into the wrist), supplies the hand. Collateral circulation
with occlusion of the distal forearm or hand vessels depends on the individual anatomy and
continuity of the palmar arches.
Acute upper extremity ischaemia
Acute ischaemia is far less common in the arm than in the leg. The difference is partially explained by
i) the extensive collateral circulation around the scapula and shoulder

ii) smaller muscle mass and metabolic needs of the arm.
The common causes are:
- Emboli (50%)
- Trauma – iatrogenic / accidental
- Hypercoagulable syndrome
- Vasospasm
- Acute thrombus superimposed on underlying pathology
- Compartment syndrome
- Others.
Chromic Upper Extremity Ischaemia
A variety of diseases may cause subacute / chronic ischaemia
- Atherosclerosis
- Thromboembolism
- Trauma
- Dissection
-Thoracic outlet syndrome
- Vasculitis – Giant cell arteritis
- Takayashu‘s arteritis
- Buerger‘s disease
- Radiation arteritis
- Aneurysm (thrombosed)
- Extrinsic compression by tumor
- Drug related causes
- Others.
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Work up of patients with suspected upper extremity ischaemia
Aim; To establish
- Presence of ischaemia
- Site of obstruction
- Nature of obstruction – fixed / spastic
- Extent of obstruction
- Status of proximal and distal vessels.
A careful clinical history and physical examination constitute the essential first steps in identifying
the problem.
Investigations
General investigations:
1. Blood: Complete blood count
- ESR
- Blood sugar
- Lipid profile
- Specific blood tests like RA factor, LE cell phenomenon
2. Urine sugar
3. ECG
4. Plain radiographs of chest and/or involved extremity may help in some cases.
Imaging:
The imaging modalities that are available are
1. Gray Scale and Doppler Ultrasonography

2. Computed Tomographic Angiography (CTA)
3. Magnetic Resonance Angiography (MRA)
4. Catheter Angiography
Gray Scale and Doppler Ultrasonography
Gray scale US is a powerful test for defining the morphology of blood vessels. Using high frequency
transducers, normal blood vessels are seen as anechoic tubular structures with thin hyperechoic
walls. An accurate measurement of the vascular dimensions is possible on the grey scale.
The direction and velocity of flow of blood within the vessels can be very well determined by duplex
Doppler sonography. The superficial location of the peripheral arteries facilitates visualization of all the
major arteries of the arm, forearm, wrist, hand and even the fingers can be subjected to Doppler
sonography. However, the proximal subclavian artery and brachiocephalic trunk may be difficult to
insonate as these vessels lie deeper in the mediastinum.
On colour Doppler, a normal artery shows pulsatile forward flow with a high resistance, triphasic
waveform on spectral analysis. With occlusive disease there is narrowing of the vessel, with aliasing
on the colour Doppler ( seen as a multitude of colors) and a high velocity, broad spectrum wave
pattern at the site of stenosis. As the stenosis progresses in severity, the velocity may decrease, and
the waveform may dampen or disappear altogether. The vessels distal to the site of stenosis show
patchy color flow with a monophasic, low velocity, low resistance waveform.
Advantages: Duplex Doppler sonography (DDUS) provides

– precise anatomic information
- locates stenotic or occlusive lesions
- evaluates their extent and severity.
- Identifies collateral pathways and
- Defines patency of arteries distal to an occlusion.
Limitations of DDUS
- operator dependant
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- subclavian artery and its origin may be less well evaluated owing to its lying deep in the
thorax and as sit passes behind the clavicle
- multilevel disease may give erroneous results
- an angiogram like picture cannot be obtained.
Status
Duplex scanning is rapidly replacing many of the cumbersome and less specific non invasive
tests. It is an excellent screening modality and is performed in almost all cases of peripheral
arterial ischaemia as a first line investigation. It is also useful in follow up monitoring .
Most clinicians still prefer to get an angiographic confirmation of the findings before surgical
intervention.
Computed Tomographic Angiography (CTA)

- Spiral CT scanning with reconstruction of axial images has made it possible to acquire
angiographic images of the vascular system with intravenous injection of contrast.
- Single slice CTA was limited by the need for tremendous longitudinal coverage for the
complete evaluation of extremity arteries. Also the spatial resolution of reconstructed images
was not as good as direct images.
- With the advent of Multislice (32 & 64 slice) CT scanners, the above limitations have been
overcome.
- CTA can be used to evaluate atherosclerotic steno-occlusive disease, embolic phenomenon,
traumatic and iatrogenic injuries, vasculitides and aneurysms.
Limitations of CTA:
- requires iodinated contrast with its inherent complications and nephrotoxicity.
- Radiation exposure.
- Limited availability of MSCT.
- Patient motion degrades study.
- Heavily calcified vessels are difficult to evaluate.
Magnetic Resonance Angiography (MRA)
Gadolinium enhanced 3D images provide excellent images of the arch of aorta as well as the entire
extremity arterial system. Earlier, non contrast enhanced sequences (2D/3D Time of flight and phase
contrast) were used to obtain the angiographic images using the inherent flowing blood to generate
images. However, their image resolution was not good and artifacts were common. Gadolinium
enhanced MRA images the contrast agent with only slight flow related enhancement and very little
image degradation from abnormal flow patterns.
The gadolinium is injected rapidly through a peripheral vein, with image acquisition timed to occur as
the contrast agent enters the arterial circulation in the region of interest. Imaging with this technique
can be accomplished in a single breath-hold, encompassing large fields of view.
There are fewer adverse reactions to gadolinium contrast agents than with iodinated contrast, and
gadolinium appears to have less clinical nephrotoxicity.
Limitations of MRA:
- Patients with cardiac pacemakers, defibrillators, metallic foreign bodies or claustrophobia

cannot be imaged.
- Heavy circumferential intimal calcification in medium or small arteries may result in artifacts
and look like apparent stenosis
- Specialized MR compatible equipment is required for haemodynamic monitoring of unstable
patients.
- Patient motion degrades study.
-
Post processing for CTA and MRA
In order to view the data from MRA and CTA studies as angiograms, electronic post processing of
source digital data is necessary. This crucial step occurs after the study has been completed, and
frequently after the patient has been removed from the scanner. A number of post processing options
266
are available (specially with CTA) ranging from simple reformatting of data into different planes (i.e.
coronal slices from axially acquired data maximum intensity projection images (MIP), shaded surface
display (SSD), volume render images with different colour coding and even an endoscopic view point
of the vascular lumbar can be obtained. Each processing technique has its inherent strengths and
weaknesses and are often complementary to each other in the final result. Status:
MRA/CTA provide a non-invasive method to establish exact site and extent of obstruction, condition of
collateral flow and condition of run off vessels. They act as a roadmap for the vascular
surgeon/interventionist to plan the therapeutic strategy.
CATHETER ANGIOGRAPHY (Film screen Angiography / Digital Subtraction Angiography )
Catheter angiography still remains the gold standard for arterial imaging. This is an invasive technique
in which a catheter is introduced via the femoral artery and positioned in the arch of aorta under
fluoroscopic guidance. Digital subtraction angiography (DSA) has almost replaced film screen
angiography. DSA uses image subtraction so that bones do not obscure vascular detail and has the
advantage of the ability to manipulate the images.
Catheter angiography makes it possible to obtain haemodynamic information across pressure

gradients. It is also possible to do interventions at the same time. However, it is an invasive procedure
as it requires intra-arterial injection of contrast and again, iodinated contrast is need.
Status:
The role of catheter angiography in the diagnosis of peripheral arterial disease has changed
substantially with the improvement and availability of non-invasive imaging techniques like CTA/MRA.
Angiography was once obtained uniformly in all patients prior to surgery or intervention. Increasingly it
is becoming a secondary imaging modality to resolve results of conflicting non-invasive tests or to
confirm an abnormality prior to percutaneous interventions.
267
Thoracic outlet syndrome
Dr. M.P.Arora
It was previously known as Thoracic Inlet Syndrome.
Definition- Thoracic Outlet Syndrome (TOS) is defined as upper extremity symptoms due to
compression of neurovascular bundle in the thoracic outlay area or superior aperture of thorax.
ANATOMY
Thoracic Outlet is the most superior aperture to the thorax and boundary of roof of mediastinum. It
slops obliquely anteriorly and inferiorly from 1st vertebral body.
Antero - Posterior Diameter: 4.5-6 cm.

Transverse Diameter : 9-11 cm.
Bony Margins :
Posteriorly – T1 vertebra
Laterally - 1st rib.
Anteriorly – 1st costal cartilage; Manubrium sterni.
RELATIONS:
Thoracic Outlet is traversed by –
In the median plane from anterior to posterior :

-Sternohyoid anterior to strernothyroid muscles.
-Thymus remnants
-Inferior thyroid vein.
-Trachea.
-Tracheo-oesophageal groove containing recurrent laryngeal nerve.
-Oesophagus
-Thoracic duct replaced to left.
-Longus colli muscles.
-Anterior longitudinal ligament.
Laterally(on both sides)

-Cervical pleura overlying apex of lungs.
-Internal thoracic artery anteriorly.
Posteriorly(from medial to lateral)

-Sympathetic trunk.
-Superior intercostal artery.
-Ventral ramus of 1st thoracic nerve.
On the left
-Left common carotid artery.
-Left subclavian artery.
-Left vagus nerve.
-Left brachiocephalic vein.
-Left phrenic nerve.
On the right
-Brachiocephalic trunk.
-Right vagus nerve.
-Right brachiocephalic vein.
-Right phrenic nerve.
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There are main spaces in the thoracic outlet area-
1. Scalene triangle- most common site for nerve compression. Contents are brachial plexus and
subclavian artery.
2. Costoclavicular space- this is traversed by all the structures-artery,veins & nerve.
ETIOLOGY1
Arterial TOS-caused by cervical rib/rudimentary 1st rib.
Venous TOS-generally due to costoclavicular ligament and subclavian muscles compressing

subclavian vein.
Neurogenic TOS- caused by narrowing of thoracic outlet & neck trauma.
The causes are-
1. Congenital-
Osseous:
-Cervical rib.
-Long C7 thoracic process.
-Abnormal or anomalous 1st rib.
-Bifid/flat clavicle.
Soft tissue:
-Anomalous anterior scalene insertion.
-Anomalous middle scalene insertion.
-Scalene muscle interdigitation.
-Scalene muscle hypertrophy.
-Scaenus minimus.
Abnormal ligaments & fibrous bands.
Brachial plexus anomalies:

- Pre-/post-fixed brachial plexus.
Postural:
-Sagging shoulders.
-Heavy breasts.
2. Acquired-
-Fracture clavicle/callus and pseudoarthrosis.

-# 1st rib.
-Exostosis or tumours.
-Scalene muscle injury.
-Previous operations & scars.
-Reattachment of anterior scalene tendon.
-Soft tissue tumors.
-Brachial plexus schwannomas.
-Direct brachial plexus injuries.
PATHOPHYSIOLOGY2
The brachial plexus trunks and vessels are subject to compression or irritations. They course through
3 narrow passageways from the base of the neck towards the axilla & proximal arm. The most
important of these passageways is the interscalene triangle, which is also the most proximal. The
triangle is bordered by anterior scalene muscle anteriorly, the middle scalene muscle posteriorly and
the medial surface of the 1st rib inferiorly. This area is small at rest and may become even smaller with
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certain provocative maneuvers. Anomalous structures such as fibrous bands, cervical rib and
anomalous muscle may constrict this triangle further. Repetitive trauma to the plexus elements,
particularly lower trunk and C8-T1 spinal nerves, is thought to play an important role in the
pathogenesis of TOS.
The second passageway is the costoclavicular triangle which is bordered anteriorly by middle third of
clavicle, posteriorly by the 1st rib and posterolaterally by the upper border of scapula.
The last passageway is the subcoracoid beneath the coracoid process just deep to pectoralis muscle
tendon.
EPIDEMIOLOGY2
Frequency-
In the US, 3-80 cases per 1000 population.
Sex-
The sex ratio varies depending on the type of TOS ( eg. Neurogenic,venous or arterial). Overall, the
entity is approximately 3times more common in women than in men.
-Neurogenic: F:M = 2:1.
-Venous: more common in males than females.
-Arterial: no sexual predilection.
Age-
The onset of symptoms usually occurs in persons aged 20-50 years.
SYMPTOMS & SIGNS
-Neurogenic- 90%.
-Vascular – 10%.
-Both neurogenic & vascular.
Neurogenic symptoms-
Paresthesia: Compression of all nerves of brachial plexus is common. Most common is ulnar
nerve and least common in median nerve.
Pain: Pain in the shoulder, arm & forearm is the hallmark of neurogenic TOS. Location of pain
depends upon which portion of brachial plexus is compressed.
Headache: occipital headache, probably due to referred pain from tight scalene muscle.
Weakness: weakness of the arms & hand is common in patients with TOS.
-Ulnar nv(C8,T1) involvement is associated with motor weakness and atrophy of hypothenar
muscles & pain and paresthesia of medial aspect of arm and hand, little finger and medial aspect
of ring finger.
-Medial nv(C5-8,T1) involvement produces symptoms in the index finger, middle finger as well as
flexor compartment of forearm.
-Also patient complains of pain in the distribution of upper three roots C5,C6,C7 with symptoms
referred to neck, shoulder, upper arm, ear, upper chest & back, outer arm in the radial nerve
distribution.
-Atypical pain in anterior chest wall or suprascapular area (psedoangina).
Symptoms due to arterial compression-

-Coldness, weakness, easy fatigability of arm & hand, ischemic pain.
-Inability to use arm above head.
-Exercise & cold precipitate these symptoms.
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-Often in young adults with a h/o vigorous arm activity.
Symptoms due to venous compression-

-Edema, venous distension, collateral formation, cyanosis of affected limbs, discoloration of arm
and hand.
Physical signs-
There are four provocative clinical maneuvers to evaluate patients of TOS. Loss or decrease of radial
pulse or reproduction of neurological symptoms is a positive test.
1.Adson‘s test-
Extend the neck fully.
Turn the neck to opposite side.
Take deep breath.
Decrease in interscalene space.
Compression of brachial artery & brachial plexus.
Paresthesia over the distribution of brachial plexus & obliteration of radial pulse.
2.Halsted test (costoclavicular test)-

Shoulders drawn downwards & backwards (military position).
Reduction of costoclavicular space with compression of vessels.
Decrease or loss of radial pulse.
3.Wright test (hyper abduction test)-
Hyper abduction of arm to 1800.
Compression of subcoracoid region.
Decrease or loss of radial pulse.
4.Roos test(Elevated arm stress test)

Arm abducted to 90o , elbow flexed to 90o& shoulder externally rotated with exercise of hands
for 3 minutes (modified Roos test).
Numbness or pain in hands & forearm.

Differential diagnoses of TOS
-Carpal tunnel syndrome. -Shoulder disorder

-Ulnar compression at elbow. -Rotator cuff injury
-Cervical spine pathology. -Biceps tendinitis
-Spinal stenosis. -Myositis of shoulder muscles
-Neurological diseases of spine. -Sympathetic disorder
-Spinal canal tumours. -Raynaud‘s disease
-Acute coronary syndrome. -Reflex sympathetic dystrophy.
INVESTIGATIONS3
1.X-ray of cervical spine: for assessment of arthritic or degenerative changes and presence of
cervical rib.
2.Chest x-ray: to identify apical lung pathology & superior sulcus tumour.
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3.Nerve conduction studies and electromyography: to delineate the possible significance of
neuroforaminal or cervical disc disease, as well as median nerve compression at the carpal tunnel
or ulnar nv compression at the cubital tunnel. The studies are very helpful in patients who have
double crush syndrome.
4.F-wave studies and somatosensory evoked responses to evaluate brachial plexus.
5.Non-invasive vascular studies- digital plethysmography and pulse volume recordings are of
limited value in neurogenic thoracic outlet syndrome. They appear helpful in patients with
ischemic symptoms. Duplex scanning of subclavian artery & vein may reveal an aneurysm or
venous thrombosis and may provide some anatomical information before angiography.
Intermittent arterial stenosis can usually be localized by B-mode ultrasound and doppler.
6.Arterigraphy: Indications are-

-evidence of peripheral emboli in upper extremity.
-suspected subclavian stenosis or aneurysm.
-blood pressure differential > 20mm Hg.
-obliteration of radial pulse during EAST.
7.Venography: Indications are

-persistent or intermittent edema of hand or arm.
-peripheral unilateral cyanosis.
-prominent venous pattern over the arm, shoulder or chest.
8.Impedance plethysmography, venous Doppler survey and venous duplex scanning can help in
diagnosing venous obstruction early.
9.C.T.Scan, Myelography, M.R.I. are done to rile out cervical spinal cord tumors, spinal stenosis or a
herniated disc. Saggital M.R.I. in the plane of brachial plexus is under investigation and in future
may provide an accurate means of assessing the point of actual compression nerves.
10.Electrophysiological Studies:-The tests are beset with technical problem because of the site of
brachial plexus as compression is often deeply situated in the confines of the bony inlet and
located proximally at the level of the nerve roots near the intervertebral foramina.
11.Ulner nerve conduction velocities in neurogenic thoracic out syndrome was popularized by
Urschel and Razzuk4. They reported decrease in ulnar nerve conduction velocities in these
patients and the nerve conduction returns to normal after surgical decompression.
Treatment:-
1. Conservative
2. Surgical Management
Conservative Treatment5
Once diagnosis of neurogenic thoracic outlet syndrome is established , an initial period of supervised
conservative treatment is instituted before operation is recommended for six weeks. It includes
analgesics, muscle relaxants , occupational adjustments to improve posture or avoid elevating the
arm during work and sleep. Physiotherapy in the form of simple heat and cold application , massages
and the ultrasonic wave application to supraclavicular area is carried out. Shoulder girdle
strengthening exercises are taught to women with poor musculature. Brassieres with broad and
padded shoulder strap is advised for women with heavy sagging breast.
Surgical Management
It is indicated if there is
a) Failure of conservative management(>4 Months2).
b) Worsening of neurogenic symptoms leading to intractable pain.
c) Loss of job or interference in daily activity.
272
d) Acute vascular symptoms.
The decision to operate should be discussed with the patient explaining the possibility of neural or
vascular complications, the possibility of achieving partial relief or recurrence of symptoms should be
emphasized when symptoms are more than two and half years duration.
Operative treatment:
The controversy surrounding Neurogenic thoracic outlet syndrome is best explained by

diversity of surgical operation available. Various combinations of operation like scalenotomy,
scalenectomy , cervical rib resection, first rib resection and neurolysis of brachial plexus may
be carried out by four approaches5.
a) Supraclavicular
b) Transaxillary
c) Infraclavicular
d) Posterier approach
Aim of operation
1. Relieving of brachial plexus symptoms

2. Any abnormal osseous structures such as cervical rib, exostosis,
abnormal first rib or fracture callous should be removed in majority of
patients.
Supraclavicular approach 6: It provides the best route to reach all the structures. It allows direct
visualization of the anatomic relationship between bony and myofascial structures and the brachial
plexus through scalene space in the thoracic outlet and related congenital anomalies along with
access to the first rib and clavicle. If the anterior scalene muscle requires decompression , it must be
excised rather than simply divided because of possible adhesions formation of perforation of the
muscle with lower nerve roots of the branchial plexus. In such cases the original symptoms would be
aggravated by the retraction of the divided muscle fibre against imbedded nerves.
Transaxillary approach 5: When the clinical picture suggest costoclavicular or hyper abduction
symptoms, surgical exploration through a trans axillary incision described by Roos and Owens is
usually preferred. Some of the advantages of axillary approach include excellent cosmesis, readily
palpable and easily visible ligaments and bony structures which may be involved in the compression
of neurovascular bundle. At the same time it allows access for dorsal sympathectomy when indicated.
Author believes that sufficient compression of the brachial plexus to produce symptoms
simultaneously causes measurable compression of the subclavian vessels even in the absence of
vascular symptoms. At operation , If the patient has been prepared so that axilla, shoulder and lower
neck are exposed with the arm draped in a sterile field, it is possible to perform hyper abduction and
costoclavicular maneuvers under anaesthesia with the thoracic outlet structures directly exposed.
Under these circumstances the physiology of the compression process and the offending structures
whether bony or soft tissue, can be identified and divided or excised. In a series of 194 patients, 14
required bone excision and 180 required soft tissue excision to re4lieve symptoms with 96% success
rate.
Infraclavicular approach : It is used for bilateral neurovascular symptoms but cosmetic results are
less favourable than other approaches. It can be used for subclavian venous thrombosis and first rib
excision.
Posterior approach : It is adopted only when there is history of previous operation by other
approach. This approach requires cutting of heavy muscles before reaching the thoracic outlet.
Rationale for sparing the first rib : The first rib is seldom in actual contact with the brachial plexus
except for T1. After neurolysis and scalenectomy, the brachial plexus runs on unobstructed course.
Resection of first rib is unnecessary and adds to post operative pain and shoulder immobility with
higher risk of pleural damage at the time of surgery.
273
Vascular thoracic outlet syndrome :
Although much less common than Neurologic TOS, it requires more urgent care.
Emergency department care:
-immediate heparinization.
-vascular surgery consultation.
-color flow duplex scanning.
-angiography or venography.
Further inpatient care-
Arterial reconstruction is necessary in the presence of arterial aneurysm or mural thrombus. Artery is
mobilized after resecting the cervical & 1st rib. End to end anastomosis is performed.
Aneurysmorraphy can be performed along with internal stenting of the subclavian artery. Distal
embolic occlusion causes major difficulties as they are multiple in number.
Thromboendarterectomy can be tried in these patients for distal emboli.
For venous thrombosis of subclavian vein, thrombolytic agents like urokinase or streptokinase are
delivered locally to dissolve the thrombus. If there is external compression demonstrated on
venography, it should relieved by supraclavicular approach.
Complications of operation for thoracic outlet syndrome7-
1.Nerve injury 2.Vascular injury

-Brachial plexus. -Subclavian artery & vein
-Long thoracic nerve. -Thoracic duct injury.
-Phrenic nerve. -Lymphatic fistula.
-Intercostobrachial nerve. -Lymphedema
-Recurrent laryngeal nerve. -Chylothorax.
3.Pleural complications 4.Wound infection.
-Pnemothorax.
-Pleural effusion.
-Hemothorax.
Prognosis:
Neurologic TOS generally neither progressive nor likely to resolve spontaneously.
Arterial or venous TOS usually results in a good outcome with adequate treatment.
References
1. Sanjay desai & Rajesh S.Thoracic outlet syndrome : Hand Book of Vascular Surgery.pg 50-60.Edition-2004.
2. Andrew K Chang et al. Thoracic Outlet Syndrome.Net Search Article-2007.
3. Michleder HI.vascular diseases of the upper extremity and thoracic outlet syndrome in : text book of vascular
surgery.A comprehensive review.Ed.Moore WS.W.B.Saunders Philadelphia-Tokyo.1993:pg592-605.
4. Urschel HC. Thoracic Outletlet Syndrome in : Glenns Text book of thoracic and cardiovascular surgery. Ed. Baue
AE. Appleton and Lange. London-NewJersey,1996;pg567-580.
5. Stallworth JM. Thoracic outlet compression syndromes in : Text book of vascular surgery. Principles and
rd
techniques. Ed. Haimovici H.W.B.Saunders Philladelphia- Tokyo 3 edition 1993;pg 829-839.
6. Richard D, Rutolo C. Neurogenic thoracic outlet syndrome in : Text book of vascular surgery. Ed. Rutherford RB.
W.B.Saunders Philladelphia-Tokyo.2000; pg 1184-1199.
7. Kieffer E. Arterial complications of thoracic outlet compression. In: Text book of vascular surgery Ed. Rutherford
RB.W.B.Saunders philladelphia--Tokyo.2000; pg 1200-1207.
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Management of Chronic Upper Limb Ischemia
Dr. (Col) Kumud Rai
INTRODUCTION
Upper extremity vascular disease is less common compared to lower extremity vascular disease,
accounting for less than 10% of all cases of chronic arterial occlusions. However it is an important
cause of morbidity in patients. A clear understanding of pathophysiology is important for the
treatment.
Upper limb ischemia (ULI) differs from lower limb ischemia (LLI) in several ways:
1. It is uncommon in comparison to lower limb ischemia. This is corroborated by the fact that
arterial reconstructions of the upper limb constitute less than 5% of all vascular
reconstructions.
2. The etiology of chronic ULI different from that of LLI. Buerger‘s disease an important
contributor to LLI, but affects upper extremity much less frequently. Atherosclerosis etiology is
common to both conditions, whereas Takayasu‘s disease, thoracic outlet syndrome (TOS),
and vasospastic disorders are the common causative factors in ULI.
3. The distinction between acute and chronic ULI tends to be blurred at times. Acute arterial
occlusions of the upper limb have a less critical effect than those of the lower limb because of
liberal collateral circulation and relatively small muscle mass, and are often missed during a
conservative ‗wait and watch‘ policy.
4. ULI is relatively commoner in females whereas LLI is predominantly seen in males.
KEY MANAGEMENT ISSUES

The management of chronic ULI involves addressing the following important issues:
Does the patient suffer from Upper Limb Ischemia?
What is the severity?
What is the level of occlusion?
What is the etiology?
What investigations should be performed?
What are the treatment options?
STEP 1. DOES THE PATIENT SUFFER FROM UPPER LIMB ISCHEMIA?
The diagnosis can be reached by a careful history and physical examination alone in the majority of
cases. Patients with ULI present with history of pain in the upper limb, Raynaud‘s phenomenon, and
digit ulceration or finger gangrene. Physical examination reveals absent or diminished pulses, except
in those with Raynaud‘s phenomenon, vasculitis or small vessel disease.
Pain. Vascular pain in the upper limb is brought about by limb exercise. The patient complains of a
dull ache, or heaviness or soreness of the limb. Upper limb claudication tends to be diffuse in contrast
to lower limb claudication which is well localized to calf, thigh or buttock. Vascular pains needs to be
differentiated from neurogenic pain which is often radiating and localized to dermatomes (e.g. inner
side of arm and forearm in C8,T1 compression, and occipital region, back of neck and shoulders in
C5-7 compression). Vascular and neurogenic pain may coexist in TOS (thoracic outlet syndrome).
Raynaud‘s disease. The attack is induced by cold or emotional distress and typically consists of three
stages: intense pallor of hand, followed by cyanosis and later hyperemia of hands.
Muscle wasting may be evident in the arm or forearm. The patient may complain that the affected
extremity has less strength than the opposite one.
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Ischemic fingers are often hypersensitive and painful. Loss of pulp in the digits may be present, and
the finger then has a characteristic tapering appearance. Capillary refill in the nail-bed is delayed.
Repeated paronychia may be a presentation. In advanced cases non-healing ulcers or gangrene may
be present.
Palpation of upper limb pulses (see below) readily confirms the diagnosis of ULI in cases which are
due to large vessel disease.
STEP 2. WHAT IS THE SEVERITY?
As in case of LLI the following features signify advanced chronic ischemia

1. Pain at rest
2. Digital ulcerations
3. Gangrene
4. Pain in the arm which prevents daily household activities (e.g. cooking or washing clothes in
case of women) also constitutes fairly severe disability.
5. Severe attacks of vasospasm with even slight cold weather also are a source of distress to
the patients.
STEP 3. WHAT IS THE LEVEL OF OCCLUSION?
As mentioned earlier, unlike the lower limb the location of claudication pain may not be a good guide
towards determining the level of block. The level of arterial occlusion can be detected clinically by
meticulous palpation of the pulses: subclavian, upper and lower brachial, radial, and ulnar. Absent
subclavian pulse indicates subclavian artery origin occlusion, commonly seen in atherosclerosis and
Takayasu‘s arteritis. In proximal subclavian occlusion, there may also be symptoms of vertebrobasilar
insufficiency (e.g. giddiness) on exercising the upper limb – the subclavian steal syndrome. A
prominent subclavian pulse or a subclavian aneurysm may be present in thoracic outlet syndrome
(TOS). Bruit may be audible in the supraclavicular region in subclavian or innominate artery stenosis.
Absent upper brachial pulse (with intact subclavian pulsations) point to axillary artery occlusion (TOS,
post-embolic etc.). Absent brachial pulse at elbow indicates brachial artery occlusion due to trauma or
thromboembolism. Absent radial or ulnar pulse may be encountered in Buerger‘s disease, post
arterial cannulation, or due to thromboembolism to forearm arteries. Intact radial ulnar pulses with
evidence of hand ischemia are found in Raynaud‘s disease and other vasospastic conditions, and in
diseases involving the small arteries.
Allen Test. The patient is asked to clench the fist and the radial and ulnar arteries are occluded
manually by the examiner. The patient releases the fist; the palm is pale. Release of compression of
the ulnar artery causes the palm to rapidly turn pink in a normal patient. Failure of this to happen
indicates an incomplete deep palmar arch. Repeating the test again, this time with release of
compression of radial artery, also confirms whether radial arch is complete or not. The test can also
be performed using Doppler Ultrasound.
Ice water immersion test. This is a useful provocative test in confirming the diagnosis of Raynaud‘s
phenomenon. Immersion of hand in ice-cold water precipitates the classical attack of pallor followed
by bluish discoloration of finger tips.
Finger temperature recovery after ice water immersion is delayed in Raynaud‘s disease. In a normal
person the baseline finger temperature returns to pre-immersion level within 5 minutes after
immersion of hand in ice water for 60 seconds. In Raynaud‘s disease this takes much longer than 5
minutes. The sensitivity of the test is in diagnosis of Raynaud‘s disease is 100%, but specificity is only
about 50% (i.e. some normal patients may show a delayed return of temperature).
STEP 4. WHAT IS THE ETIOLOGY?
The etiological factors of ULI can be broadly classified into Obliterative and Vasospastic (Table1).
This distinction is important because occlusive lesions of larger vessels are amenable to surgical
bypass or angioplasty, whereas vasospastic conditions are managed medically. It should be
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remembered that these are not watertight compartments: patients with vasospastic disease may also
develop arterial obstruction in small vessels during the course of the disease.
Table 1. Etiology of Upper Limb Ischemia

Obliterative
Atherosclerosis
Takayasu‘s arteritis
Thoracic Outlet syndrome
Trauma (crutch injury, arterial cannulation, radiation arteritis)
Fibromuscular hypoplasia
Vasospastic
Raynaud‘s disease
Vibration finger
Acroyanosis
________________________________________________________________________
Another way of addressing at the problem is to study the pattern of distribution of disease. Chronic
upper limb ischemia falls into six broad anatomical patterns:
1. Central causes: Delayed presentation of emboli from the heart lodging in the upper extremity
vessels.
2. Occlusion of vessels at the arch: atherosclerosis, Takayasu‘s arteritis
3. Causes at the root of the limb e.g. thoracic outlet syndrome
4. Local causes: radiation injury, trauma, post-cannulation occlusion etc.
5. Peripheral disorders affecting the small vessels of the hand: Raynaud‘s and Buerger‘s
diseases, thermal or vibration injury
6. Generalized systemic disorders e.g. arteritis or vasculitis
A careful history taking is of utmost importance. Co-morbid conditions: pre-existing heart disease,
diabetes mellitus, dyslipidemia and hypothyroidism should be enquired about. Details regarding
smoking / tobacco consumption are obtained. A history of previous episodes of arterial or venous
thrombosis may give a clue for thrombophilia. A history of occupational exposure to vibratory tools or
chemicals (e.g. vinyl chloride), repeated trauma (hypothenar-hammer syndrome) or drugs (e.g. ergot /
cannabis) is specifically asked for. Symptoms of collagen disorders: myalgia, rashes, arthralgia,
morning stiffness, recurrent oral ulcers, weight loss, easy fatigability, low grade fever, xerostomia /
xeropthalmia and dysphagia are enquired.
STEP 5. WHAT INVESTIGATIONS SHOULD BE PERFORMED?
The choice of investigations depends on the suspected etiology. Recording of arterial pressures using
a hand-held Doppler is a basic investigation. Of the following available investigations, Color Doppler
and some form of angiography is required when large vessel disease is present. Pulse volume
recording and digital plethysmography is performed when vasospastic or small vessel disease is
suspected. Collagen disorders and arteritis mandate an entirely different set of tests. Plain X rays,
nerve conduction studies, and MRI are required when TOS is suspected.
Doppler arterial pressure recording. Doppler pressure recording at various levels (arm, forearm, digital
arteries) helps in confirming the diagnosis, localizing the level of the block, and can also indicate the
severity of the disease. A pressure difference of 20 mm Hg or more between the two limbs is
considered significant. Finger pressure recording using special cuffs is useful in detecting digital artery
occlusion.
Color Doppler scan. As with lower limb ischemia, the color Doppler (duplex) scan gives excellent
resolution pictures and is the imaging modality of choice. It is particularly useful when large vessel
occlusive disease is present. It is the initial investigation of choice in assessment of chronic ULI.
Pulse waveform analysis. Qualitative analysis of the waveforms using photoplethysmography has
been used in diagnosis of Raynaud‘s disease. The normal pulsatile pattern is lost and the waveform
becomes either ‗peaked‘, or dampened with a delayed upstroke.
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Cervical spine X Ray / Chest X Ray. This is required when TOS due to cervical rib is suspected. It
may also reveal cervical spine pathology causing pain in the arm.
Nerve conduction studies. These are useful in suspected neurogenic TOS, where they are often
abnormal. Normal nerve conduction velocities do not exclude TOS.
MRI/MRA. Magnetic resonance imaging is emerging as the modality of choice in evaluating soft tissue
anomalies associated with TOS, especially where a cervical rib is not present. It also excludes (or
demonstrates) prolapsed cervical disc as the cause of brachialgia.
Arteriography. Digital subtraction angiography (DSA) is rarely performed for diagnosis alone, though it
may be indicated to confirm small vessel occlusive disease if other tests are inconclusive. It is
employed when surgery / angioplasty is planned. Non-invasive modalities like MR Angiography and
CT angiography are increasingly being utilized for diagnostic purposes.
Blood tests: ESR is usually elevated in collagen / autoimmune disorders, and an associated
normochromic anemia is usually found. C Reactive protein (CRP) has also been used to monitor the
activity of the disease. Rheumatoid factor is positive in rheumatoid arthritis. Presence of antinuclear
antibodies (ANA) indicates SLE. Positive antinuclear factor supports the diagnosis of CREST
(Calcinosis, Raynaud‘s disease, Esophageal dysmotility, Sclerodactyly, and Telengiectasia)
syndrome. If a hypercoagulable state is suspected, thrombophilia profile should be asked for Protein
C & S, antithrombin III, serum homocystine, lupus anticoagulant, anticardiolipin and antiphospholipid
antibodies, lipoprotein (a), factor V Leiden, MTFHR mutation).
STEP 5. WHAT ARE THE TREATMENT OPTIONS?
In general, the options are available are conservative treatment (including pharmacotherapy), direct
arterial surgery (thrombectomy / bypass), sympathectomy, and angioplasty (with or without stenting).
It is difficult to issue generalized guidelines for the diverse etiologies causing ULI. A brief description
of individual conditions and their management follows.
Atherosclerosis
Clinical presentation
The usual site of atherosclerotic occlusions is in the supra-aortic trunks. Patients with proximal
subclavian artery occlusion (which is much more common on the left side) present with upper limb
claudication, and an absent or feeble pulse is found on clinical examination. Symptoms are usually
mild due to liberal collateral circulation. Rest-pain and ulceration are exceedingly rare and indicate a
multi-level occlusion. Patients may also present with symptomatic subclavian steal phenomenon:
vertebrobasilar symptoms (e.g. giddiness) on arm exercise. This is due to reversal of flow in left
vertebral artery (via the circle of Willis) during exercise. More common is the radiological subclavian
steal seen on angiography; this does not require any treatment in an asymptomatic patient. Stenosis
of brachiocephalic trunk is not uncommonly seen on arch angiography. It rarely causes distal
embolization, and complete occlusion is rare. Atherosclerotic disease of left common carotid artery
origin is exceedingly rare in comparison to the much more common carotid bifurcation stenosis.
Treatment
Medical management of atherosclerosis is mandatory, and has been outlined in previous chapter
(abstinence from tobacco, aspirin, and statins). Many patients with left subclavian occlusion do not
require surgery as symptoms are mild. Surgical options include: (1) carotid subclavian bypass using
PTFE graft, (2) subclavian – common carotid transposition, or (3) extra-anatomic bypass in the form
of axillo-axillary bypass. Alternatively, angioplasty and stenting of the lesion can be performed. This is
an excellent minimally invasive procedure with results comparable to surgery, and a low complication
rate (distal embolization or stroke in vertebral artery territory). Thoracotomy and endarterectomy of
brachiocephalic or left CCA occlusion is now largely historical. Angioplasty / stenting or axillo-axillary
bypass can be performed, though the indication for such a procedure is uncommon.
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Takayasu‘s Arteritis
Introduction
Mikito Takayasu, a Japanese ophthalmologist described this condition in 1908. Alternative
nomenclature includes middle aortic syndrome, pulseless disease, young female arteritis, non-specific
aorto-arteritis and aortic arch syndrome. This is an inflammatory arteritis of large arteries (aorta or its
major branches) seen mostly in females under 40 years of age. Common in Japan, Asian countries
and South Africa, the disease is rare in the Western world. Incidence in Japan is 300 / million while
that in USA is 2.6/ million.
Etio-pathology
Despite a suggested tubercular, rheumatic carditis and streptococcal etiology, the disease is a distinct
clinical entity. It may also be seen in several autoimmune diseases. The initial lesions are seen in
vasa vasorum; there is early inflammation of media by lymphocytes, granulocytes, and other
inflammatory cells, with a picture of ‗pan-arteritis‘. This leads to destruction of elastic component of
media and subsequent fibrosis of medial smooth muscle, and aneurysm formation (in addition to
occlusion). Cytokines like Interleukin 6 (IL 6) and RANTES (regulated as chemokine activation,
normal T cell expressed and secreted) are produced; their measurement in serum may lead to
diagnosis.
Clinical features
The disease is almost exclusive to females, though 25% patients of male sex have been reported
from India. The vast majority (>90%) are under 40 years of age. The following features may be
present:
1. Upper extremity claudication. Absent or feeble upper limb pulse is seen in over 90%.
2. Cerebrovascular symptoms: stroke (20%), transient blindness, syncope and dizziness.
3. Hypertension is seen in more than 70% cases. It is mostly due to renal artery stenosis, and
sometimes due to aortic coarctation. It may be present without these conditions.
4. Lower extremity claudication is rare.
5. Visual involvement is seen in 20-30% cases.
6. Aneurysm formation: Very common in South Africa (70%), common in Japan (30%) and
India, and rare in USA.
7. Cardiac involvement: Congestive cardiac failure due to aortic valve insufficiency,
pulmonary hypertension due to pulmonary artery involvement, and coronary artery lesions.
Classically, three distinct phases have been described in the natural history of the disease.
There may be an overlap though between the stages.
1. Early systemic phase; patients complain of vague malaise and constitutional symptoms.
2. Phase of vascular inflammation, leading to vascular damage.
3. ‗Burned out‘ phase, when features of disease activity have subsided.
Investigations
Complete blood count: This usually reveals anemia, leukocytosis, and thrombocytosis, either alone or
in combination.
Markers of systemic illness: ESR (erythrocytic sedimentation rate) and CRP (C-reactive protein) are
mandatory for diagnosing active disease and for monitoring disease activity during pharmacotherapy
and follow-up. IL-6, and RANTES are still not available for clinical use.
Duplex scanning is the standard initial non-invasive investigation, and can confirm the diagnosis in the
vast majority. It is also used for monitoring disease activity (measurement of arterial wall thickness.
Angiography. DSA remains the gold-standard in diagnosing Takayasu‘s arteritis, and planning
treatment, whether endovascular or surgical. The angiographic classification of Takayasu‘s arteritis is
outlined in the table. MR angiography and CT angiography have the advantage of being non-invasive,
and are increasingly being used in diagnosis.
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Table 2. Angiographic Classification of Takayasu‘s Arteritis (Tokyo International Conference)
Type I Aortic arch branches (brachiocephalic, subclavian, carotid)

Type IIa Aortic arch & its branches + ascending aorta
Type IIb Aortic arch & its branches + ascending aorta + descending thoracic aorta
Type III Descending thoracic aorta + abdominal aorta + visceral / renal arteries
Type IV Abdominal aorta + visceral / renal arteries
TypeV Entire aorta (IIb + IV)
C+ / P+ May be added in any category in case of coronary or pulmonary lesion
Diagnostic criteria
Various diagnostic criteria have been used e.g., Ishikawa‘s criteria, or those of America
Rheumatology Association. Sharma‘s criteria, essentially a modification of the former (adding serial 3
in ‗Major Criteria‘, and serial 10 in ‗Minor Criteria‘, and deleting ‗Age < 40 years‘) are presented in
Table. 3 major criteria, or one major and 2 minor criteria, or four minor criteria are essential for
diagnosis.
Table 3. Sharma‘s Criteria for diagnosis of Takayasu‘s arteritis
Major Criteria Description

1. Left mid-subclavian lesion
2. Right mid-subclavian lesion
3. Characteristic Symptoms & Signs Upper limb claudication, absent / diminished
pulse, > 10 mm Hg BP difference between two
limbs, fever, neck pain, blurred vision, syncope,
amaurosis fugax, dyspnoea, palpitation
Minor Criteria
1. Raised ESR Unexplained ESR > 20 mm Hg
2. Carotid tenderness
3. Hypertension
4. Aortic regurgitation
5. Pulmonary artery disease
6. Left mid common carotid lesion
7. Distal brachiocephalic trunk lesion
8. Descending aorta lesion
9. Abdominal aorta lesion
10. Coronary artery lesion Patient < 30 yrs; no risk factor for CAD
Treatment
The management of disease is primarily medical.
Medical.
Prednisolone in a dose of 1 mg / kg / day is the initial drug of choice, and should be continued
in a lower (maintenance) dose till the active phase of the disease is well controlled. This may
take several months or years. Cytotoxic drugs (methotrexate, cyclophosphamide,
azathioprim) may be indicated. The current trend is for early addition of these agents, if
steroids cannot be stopped or tapered within 3 months. Methotrexate is the best agent. Anti-
tubercular treatment. The practice of prescribing ATT for Takayasu‘s arteritis in this country is
not backed by scientific evidence.
Surgical.
Surgery is indicated in management of aneurysmal as well as occlusive disease. It is prudent
to wait till the disease activity has subsided. Endarterectomy may not be feasible. Bypass
surgery using reversed saphenous vein or synthetic grafts may be required. Angioplasty has
been tried for occlusive disease. Because the lesions are long, angioplasty was thought to be
contraindicated. Several reports indicate its feasibility and success, not only for short-segment
disease (e.g. renal artery stenosis), but also in some cases of long segment occlusions.
Recalcitrant lesions may be dilated using ‗cutting balloons‘. Stenting these lesions do not
seem to add any benefit.
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Thoracic Outlet Syndrome
Introduction
Thoracic outlet syndrome (TOS), also called the scalenus anticus syndrome, costoclavicular
syndrome and hyperabduction syndrome, is defined as upper extremity symptoms due to
compression of neurovascular bundle in the thoracic outlet area. The three elements of neurovascular
bundle - nerves, artery and vein - can be compressed separately and distinct symptom complexes are
thus produced, resulting in neurogenic, venous or arterial TOS. Neurogenic TOS is the most common
form constituting more than 95% of cases. Venous and arterial TOS together account for the
remaining 5% of cases.
Anatomy
The thoracic outlet is bounded by manubrium sternum anteriorly the spine posteriorly and the first rib
laterally. The interscalene space is bounded by the anterior scalene muscle anteriorly the middle
scalene muscle posteriorly and the first rib inferiorly. The costoclavicular space is bounded by the
clavicle and the subclavius muscle anteriorly, the anterolateral border of the first rib medially and the
scapula posteriorly. The subclavian artery, vein and the brachial plexus pass from neck into the upper
extremity through these spaces, where they are liable to get compressed.
The first rib is strategically located. It is the only bony structure to border the three anatomic spaces
through which the neurovascular bundle passes. It also serves as the osseous framework to which
muscles and ligaments are attached. It is hypothesized that the first rib is the common denominator
against which the various structures compress the neurovascular bundle and the removal of the first
rib will ameliorate all the symptoms.
Etiology of TOS
The various etiological factors are listed below in the Table 4. The incidence of cervical rib varies from
0.45% to 1.5%. Gruber classifies cervical rib into four types: (a complete fibrous band, a rib ending
with a tapering point connected to the first rib by a fibrous band, the free end of the rib expanding into
a bony mass, or a complete rib articulating with the manubrium/ first rib). Cervical ribs are common,
and its mere presence in a patient with upper limb pain does not establish a diagnosis of TOS.
Table 4. Etiological factors in thoracic outlet syndrome

Congenital
Cervical rib
Abnormal first rib
Soft tissue anomalies (myo-fascial bands, anomalous scalene muscle insertion)
Brachial plexus anomalies (‗post-fixed‘ plexus)
Acquired
Fracture first rib, clavicle
Bony exostosis / tumor, or soft tissue tumor
Previous surgery / scars
Scalene muscle injuries / hypertrophy
Drooping shoulders
Clinical Presentation and Management
Neurogenic TOS
Clinical features. Patients with neurogenic TOS are usually women in their 2nd to 4th decade of life.
Onset is usually insidious but occasionally may be abrupt and related to a specific incident Pain is the
predominant symptom of neurogenic TOS. When upper brachial plexus roots are involved, the pain is
localized to the lateral aspect of arm and shoulder area, ipsilateral headache and facial pain. Lower
root involvement produces pain in the inner aspect of the arm and the forearm of an ulnar nerve
distribution. The symptoms are aggravated by elevation of arm, or when it is employed for daily
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chores like cooking, washing clothes etc. Less constant complaints include a sense of clumsiness in
the hands and fingers, episodic temperature changes or Raynaud‘s phenomenon in the digits.
Several clinical tests have been described. They aim to mimic patients‘ symptoms during specific
maneuvers.
1. Supracalvicular tenderness on direct pressure over scalenus anterior muscle / brachial plexus is
often present. A positive response may also reproduce the symptoms of pain and paresthesiae
radiating from the neck down to the arm.
2. EAST (Elevated arm stress test) described by Roos is fairly reliable. The patient is asked to fully
elevate the shoulder and arms and then clench and unclench the hands. Patient with neurogenic TOS
complain of pain, weakness and paresthesiae in ulnar and median nerve distribution, and are unable
to continue beyond 3 minutes.
3. Abduction external rotation (AER) test. The patient is instructed to place both the hands in 90
degrees of abduction and external rotation with the shoulders braced posteriorly and is then asked to
open and close the hands slowly for 3 minutes. Most patients with TOS are unable to complete the
test.
4. Adson‘s test: The patient is seated with arms by the side, the elbows flexed and hands resting
comfortably in his lap; the examiner is seated opposite and palpates both radial pulses. The patient is
then asked to elevate the chin and turn the head away from the affected side while taking a deep
breath. A positive response produces obliteration of the ipsilateral radial pulse. The Adson‘s test is
presently considered unreliable; false negatives are common in TOS, and false positives in normal
subjects are frequent.
5. Costoclavicular maneuver: the radial pulse disappears on bracing the shoulders backwards and
downwards in a ‗military attitude‘ position. This aims to demonstrate compression of the subclavian
artery in the costoclavicular space. Its value is also questionable.
6. Hyperabduction test: the radial pulse disappears on abducting the shoulders. This is due to the
compression of the axillary artery by pectoralis minor muscle on hyper abduction.
7. Brachial plexus tension test (Elvey): Quite like the sciatic stretch test of the lower limb, a series of
maneuvers are employed to put the brachial plexus to tension by abducting the flexed arm followed by
external rotation, extension of elbow, and finally wrist extension, and this reproduces patient‘s
symptoms.
Investigations.
Cervical spine X Ray, MRI and nerve conduction studies are useful in the diagnosis of neurogenic
TOS; they also help to exclude other common causes of arm pain – carpal tunnel syndrome and
cervical spine disease. Arteriography (demonstration of compression of subclavian artery in
hyperabduction) should not be used to diagnose neurogenic TOS!
Differential diagnosis
Cervical spine pathology: spondylitis/herniated disc
Carpal tunnel syndrome
Shoulder disorders e.g. rotator cuff tendinitis
Raynaud‟s disease
Treatment.
The treatment of neurogenic TOS is mainly conservative, in contrast to that of arterial and venous
TOS which is operative. Conservative treatment consists of a short course of analgesics to relieve the
pain. This is followed by an exercise programme to strengthen to relax the muscles that tighten
thoracic outlet (middle scalene, subclavius and pectoralis), while strengthening those which relax
thoracic outlet (trapezius, levator scapulae and sternocliedomastoid). Patients must be taught to
improve the posture and to avoid lifting weights and to avoid hyperabducting the shoulder. This
exercise programme must be continued for at least six weeks, before evaluating results. Therapeutic
blockade of scalene muscles using steroids and botulinum toxin has also been tried with mixed
results.
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Surgery is reserved for the patient who fails to respond to conservative treatment and continues to be
severely symptomatic. If a cervical rib is present this should be excised, and a scalenectomy of the
scalenus anticus performed. Soft tissue anomalies (fibrous bands, accessory muscle slips etc.) should
be carefully searched for and removed. If no cervical rib is present the first rib should be excised
(along with scalenectomy). The approach for these surgical procedures could be supraclavicular or
trans-axillary; the former is more popular with vascular surgeons. Surgery was an extremely popular
option for management of neurogenic TOS till a few years ago; however recent reports indicate a
rather poor outcome after surgery with symptoms persisting in a large number of patients. Caution is
therefore strongly advocated in offering surgery.
Arterial TOS
Clinical features. These patients are usually older (compared to neurogenic TOS), and there is less
female predominance. The presentation may be acute or subacute. Acute upper limb ischemia
(sudden onset severe pain, pallor, paresthesiae, paresis and absent brachial / radial pulse) with a
pulsatile supraclavicular mass and/or bruit is the classical presentation of arterial TOS. Often the
presentation is subacute with a painful limb, claudication, and coldness / colour changes in the hand.
Investigations. An initial portable Doppler arterial pressure recording is followed by a colour Doppler
study and arteriography. Chest / cervical spine X Ray may reveal a cervical rib.
Treatment. If there are clinical features of severe limb ischemia and threatened limb loss emergency
surgery may be required. More commonly surgery can be planned as a semi-emergency. The patient
is heparinized initially. For surgery, the cervical approach is employed. Excision of aneurysmal /
ecstatic portion of subclavian artery and restoration of continuity by end-to-end anastomosis or with a
suitable graft (synthetic/venous) prevents further episodes of distal embolization. This is combined
with scalenectomy and excision of cervical rib (if present) or the first rib. Cervico-dorsal
sympathectomy can also be performed through the same incision. Distal thromboembolectomy or
bypass surgery may be required if indicated.
Venous TOS
Clinical features. Patients are usually young and healthy males and present with sudden onset of arm
pain, swelling and cyanosis. This usually follows some type of repetitive activity such as pitching a
baseball, house painting, swimming, rowing a boat etc. and has been called the ―Pager-Schroetter‘s‖
or ―effort thrombosis‖ syndrome. Rarely the patient may have a chronic presentation with periodic /
transient arm swelling and pain when the arm is abducted or the shoulders hyperextended.
Investigations. Venography is indicated; this reveals thrombosis of the subclavian / axillary vein(s).
Chest / cervical spine X Ray may reveal a cervical rib.
Treatment. The treatment has veered from the conservative one advocated in the past (rest to the
limb, analgesics, and heparinization/anticoagulation) to a more aggressive approach, more so if the
patient with subclavian vein thrombosis presents early. Catheter directed thrombolysis of subclavian
and axillary veins followed by surgical removal of offending structure (first/cervical rib) along with
scalenectomy rapidly resolves symptoms, and prevents long-term sequelae (chronically swollen limb).
Outcome
In neurogenic TOS resection of cervical rib or first rib with scalenectomy offers better results than
scalenotomy alone. However the enthusiasm of seventies and eighties in surgical management of
neurogenic TOS has been considerably dampened by reports that success rate (relief of pain) is poor
if this is employed indiscriminately. The patient should be warned that the success rate is only about
80%, even in best of circumstances. The results of surgical treatment in arterial and venous TOS are
much better. However arterial TOS may still be left with some residual deficit if the initial insult was
severe.
Raynaud‘s Syndrome
Raynaud‘s syndrome, first described by Maurice Raynaud in 1862, is defined as episodic digital
ischemia occurring in response to cold or emotional stress. The patient presents with classical
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triphasic colour changes in fingers as described earlier. Traditionally patients with Raynaud‘s
syndrome have been divided into two subgroups: those with ‗Raynaud‘s disease‘, or those with
‗Raynaud‘s phenomenon‘.
Raynaud‘s disease refers to patients with intermittent digital ischemia in the absence of an associated
disease, and is thought to be due to an intrinsic abnormality in digital vessels, sympathetic nervous
system, or thermoregulatory mechanism. This is a vasospastic condition; the arteries are structurally
normal. It is seen in young females.
Raynaud‘s phenomenon is used to describe patients who manifest digital ischemia due to an
underlying disease, usually a connective tissue disorder. These patients may have palmar or digital
artery occlusive disease in addition to the spastic element. A detailed description of individual
conditions is beyond the scope of this chapter.
It is worth remembering that patients with Raynaud‘s disease may turn out to have some underlying
pathology during follow-up, and lately pleas have been made to abolish this distinction. Etiological
factors are mentioned in the table 5 below.
Table 5. Etiological factors in Raynaud‘s syndrome
Primary (Raynaud‘s disease) Vascular Disorders

Connective tissue disorders Atherosclerosis
Scleroderma TAO (Buerger‘s disease)
SLE Thoracic outlet syndrome
Rheumatoid arthritis Arteritis
Sjogren‘s syndrome Fibromuscular disease
MTCD/UCTD Hypersensitivity angiitis
Drugs Occupation
Ergotamine Vibration arterial injury
Oral contraceptives Cold exposure
Cytotoxic drugs Miscellaneous
Beta blockers Malignancy
Neurological/endocrine disorders
MTCD, Mixed connective tissue disease
UTCD, undifferentiated connective tissue disease
Clinical evaluation
The ice water immersion test and finger temperature recovery time (following ice water immersion)
are diagnostic, and have been described in detail earlier.
Hematological tests to be performed when underlying connective tissue disorder is suspected have
been mentioned in ‗Step 5‘. Additional tests may have to be performed for connective tissue
disorders: anticentromere / tropoisomerase antibodies (scleroderma), HLA-DRW-4 (rheumatoid
arthritis), antibodies to ribonucleic acid protein (MTCD). Appropriate biopsy may also be indicated in
addition for diagnosis of connective tissue disorders.
Angiography. DSA may be indicated when occlusion of small vessels of hands needs to be confirmed.
Management
General measures. The vast majority of patients can be managed by conservative measures alone.
Avoidance of cold is mandatory, as is tobacco abstinence. Simple measures like wearing gloves are
adequate for the majority of cases. Thermally heated gloves are now available, and are useful in
patients whose attacks are not controlled by ordinary gloves.
Pharmacotherapy. Several drugs are available.
Nifedipine. This calcium channel blocker is the most effective drug to date in relieving or
improving symptoms in vasospastic Raynaud‘s syndrome. Dose: 30 – 60 mg/day, preferably
in sustained release formulations.
Losartan, an angiotensin II type I receptor antagonist has also been shown to be effective in
randomized trials. Dose: 25 – 100 mg / day.
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Fluoxetine, a selective serotonin reuptake inhibitor has shown benefit in a double blind
randomized controlled trial. Dose:
Other drugs used in the management include Thymoxamine (40 mg qid), Diltizem (120-300
mg/day), reserpine (0.25-1mg/day), captopril, guanethidine (10 mg/day), prazosin (1-2
mg/day) ketanserine, local nitroglycerin patches or ointment, niacin, omega-3 fatty acids, and
dibenzylamine. Patients with digital ulcerations may benefit from reserpine given intra-
arterially or as regional intravenous anaesthesia (Bier‘s block). Intravenous prostaglandin
infusion (6ng/kg/hr increasing to 15ng/kg/hr) is also useful.
Surgery. Cervicodorsal sympathectomy has been used in the management of digital vasospasm as
well as ulcerations. It is very effective in relieving vasospasm, but symptoms invariably recur within
about 6 months. Its role in management of ulceration is unclear, with most authorities not favouring it.
The operation may be performed via a thoracotomy, supraclavicular approach, or more commonly by
laparoscopic thoracic approach.
Other approaches include periarterial digital sympathectomy, biofeedback, and epidural spinal cord
stimulation; none of these have been found be effective in rigorous clinical trials.
Prognosis
Prognosis in Raynaud‘s syndrome depends on the etiology. Those without an underlying obstruction
of digital arteries or connective tissue disorders have an excellent prognosis, with an extremely low
risk of developing finger ulceration. Patients with occlusive disease but no evidence of associated
connective tissue disorders have a 10% chance of developing an associated disease in the next
decade, and have a 50% probability of developing ischemic ulcers. Patients with both – small vessel
occlusive disease and connective tissue disorders – are likely to develop fresh or recurrent ulcers in
about 60% of cases.
Other Vasospastic Conditions
Vibration White Finger is seen in workers in steel industry, welders, miners, and road and
construction workers who are exposed to vibration from hand-held powered tools like chain-saws,
drills, and grinders. After a variable period of using these tools patient develops a painful white finger
on exposure to cold. Severity of symptoms is variable, but ulceration and gangrene are uncommon.
There is no treatment other than avoiding exposure to cold, and a change of profession in severe
cases.
Acrocyanosis is seen exclusively in females. Patients present with oedema, coolness, and cyanosis
of hands, feet and legs. This is attributed to cutaneous arterial vasospasm.
Livedo reticularis is characterized by cyanotic mottling of skin of hands and wrists, or the feet and
lower legs on exposure to cold. This has been attributed to arteriolar spasm with secondary dilatation
of venules. Cold exposure is to be avoided. Sympathectomy is of benefit in this condition.
Erythromealgia is a condition where, in contrast to Raynaud‘s disease, heat provokes an attack of

burning pain in hands and feet often associated with colour changes. Patient seeks relief by walking
barefoot on a cold floor. Beta blockers and carbamazepine may prove useful.
Chilblains is attributed to hypersensitivity to cold. Patients complain of pain, cyanosis and swelling in
fingers on exposure to cold.
Miscellaneous conditions
Hypothernar hammer syndrome. The syndrome typically occurs in labourers, and follows repeated
use of hand in pounding, pushing, or twisting motion. Repeated trauma leads to aneurysm formation
of the distal ulnar artery at a point just beyond volar carpal tunnel (Guyton‘s canal), where it lies
anterior to the hook of hamate bone. Patient presents with symptoms of Raynaud‘s syndrome, but the
thumb is characteristically spared. Diagnosis is by angiography. Treatment is resection of aneurysm
and restoration of continuity of the artery using microsurgical techniques. Intra-arterial thrombolytic
therapy may be used to restore flow in a thrombosed aneurysm in an acute setting, and this should be
followed by definitive surgery.
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Management of acute upper limb ischaemia
Dr. Rajiv Parakh
Etiology
Occlusive causes (More commonly occurring causes)

a. Intrinsic obstruction
i. Emboli originating in the heart
1. mitral stenosis
2. atrial fibrillation
3. myocardial infarcts
ii. Arterioarterial embolization
1. aneurysms
2. atherosclerosis( most common cause of arterioarterial
thromboembolism)
3. iatrogenic
a. arterial pressure monitoring
b. blood gas analysis
c. transluminal angioplasty
d. intra-arterial infusions
e. drug abuse
b. Extrinsic obstruction
i. Penetrating arterial injury
1. laceration
2. transaction
3. mural contusion and severe spasm
ii. Fractures of long bones or dislocations
1. Mechanism : compression, angulation, kinking, contusion, laceration,
transaction
2. Arteries are most vulnerable where they are relatively fixed by
muscle or fascia.
iii. Extensive neoplastic or inflammatory masses causing compression and
vascular insufficiency
iv. Compartment syndrome
Non Occlusive causes (Less common causes)
c. Low flow states
i. Cardiac disease
ii. Endotoxaemia
iii. Debilitating disease
iv. Extensive neoplasia
d. Drugs ( cause low cardiac output and splanchnic vasoactivity)
i. Corticosteroids
ii. Digitalis
iii. Phenothiazine
Pathophysiology
Embolus or in situ thrombus lodge most commonly at a point where major vessels branch. The distal
circulation becomes sluggish and with the frequently attending hypercoagulability state, distal
extension of the thrombosis is likely.
Ischaemia leads to hypoxia which causes inefficiency of ATP dependent sodium pump to maintain
electrolyte gradient across the membrane. Consequently sodium moves inside the cell along with
water. This leads to cellular swelling. Also free radicals generated as a result of ischaemia lead to lipid
peroxidation of cell membranes leading to changes in cell membrane permeability and cell swelling.
The outcome following a period of ischaemia depends upon:

1. specific tissue tolerance to hypoxia : Nerves and muscle tissue have relatively less resistance
to ischaemia than skin
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2. Duration of circulatory interruption : irreversible changes in muscles and nerves after 4-6
hours of ischaemia
3. Presence of collateral circulation
4. Efficiency of reflow phenomenon : Impaired reflow phenomenon due to:
a. Narrowing of vascular lumen secondary to compression by swollen cells
b. Vascular trapping of red blood cells in the narrowed capillaries
c. Capillary occlusion by leukocyte plugs
Clinical Manifestations
Five cardinal features:

 Pain
o Pain is usually well localized, and severe.
o May not be prominent in patients with relatively good collateral circulation.
o Also when onset is very sudden anesthesia intervenes without pain ever developing
 Paralysis
o Subtle degrees of weakness of muscles of feet or hands
o Helps in determining viability
 Paresthesia
o Light touch and proprioception lost early
o Sensations of pressure, pain and temperature remain
 Pallor
 Pulselessness
o Distal pulses are absent.
o Sometimes even with distal circulation, distal vessels are not palpable owing to tissue
edema.
o Also, occasionally distal pulses are present despite proximal vascular occlusion due
to collaterals. Hence palpable distal pulses do not preclude ischemia.
Other Signs:
 Cool limb almost empty of veins
 Tenderness overlying the acute embolus
 Prominent pulsations of immediately proximal arteries
 Consistency of skeletal muscles changes with increasing ischemia: from soft and elastic they
feel thick and inelastic and when necrosis sets in they feel stiff and firm. An indication that
revascularization process will fail.
 Evidence of other associated diseases:
o Preexisting cardiac disease
o Segmental a therosclerosis
o History of intermittent claudication
Diagnosis
Diagnosis is by physical examination in many cases of acute superficial arterial thrombosis. In cases
of severe ischemia when the clinical diagnosis is firm and solid indications for surgical management
exist a delay for arteriography may be unwise.
 Arteriography
Indications for arteriography
1. With moderate ischemia when doubt exists as to the exact nature of occlusion
2. When one cannot separate patients with emboli from thosewho have in situ thrombosis
3. Delayed arteiograms of distal circulation to assess patency of distal vascular tree.
 Doppler studies
 Echocardiography
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Management
Adequate hydration
Temperature maintenance of the affected limb
Systemic heparin therapy
Local infusion of heparin intraoperatively where systemic anticoagulation is not possible
Maintenance of potassium levels by administering glucose with insulin, ion exchange resins etc.
Mannitol for reducing edema and to promote diuresis once adequate volume have been restored.
Sodium bicarbonate to counter acidosis
Treatment Options:
Non traumatic ischaemia:
Conservative management:
On many occasions if the limb appears viable and the patient does not have severe pain, the
ischaemic upper limb may be treated conservatively.
In cases of axillary arterial injuries with concomitant brachial plexus injuries, sometimes it may be wise
to treat conservatively unless there is imminent threat of loss of limb, which is usually uncommon in
axillary arterial injuries.
Embolectomy
Embolectomy is the most frequently performed surgical procedure for acute upper limb ischaemia.
Occasionally nonviable digits may require amputation. The introduction of a Fogarty's balloon catheter
in 1963 revolutionized the treatment of acute limb ischaemia. Usually under local anaesthesia.
 Display and control arteries with slings
 Transverse artereotomy performed over common femoral artery
 Fogarty balloon embolectomy catheters used to retrieve thrombus
 If embolectomy fails - on-table angiogram and consider
 Bypass graft or intraoperative thrombolysis
Other modalities of management:
A. Endovascular Options
1) Regional intraarterial thrombolysis:
Indications:
Patients with I ischaemia with no imminent danger of limb loss may be candidates for thrombolysis.
The treating physician must make this determination on a case-by-case basis. Patients with severe
limb threatening ischemia should not be treated percutaneously because catheter- based thrombolytic
therapy often takes many hours and threatened ischemic changes may become irreversible over the
course of treatment.
Important questions to consider before undertaking therapy include whether: (i) the patient can
tolerate the anticipated time of treatment, (ii) the total clot burden is suitable for thrombolysis in a
reasonable length of time, (iii) the clot location is within reach of the thrombolytic catheters/devices,
and (iv) the patient has risks of thrombolysis / anticoagulation that outweigh the benefits of the
thrombolytic therapy.
Agents: Urokinase, Tissue Plasminogen Activator
2) The percutaneous aspiration thrombectomy.

This technique uses a large bore catheter connected to a syringe to aspirate clot from vessels. This
tech-nique, first described by Sniderman et al can be used alone or in conjunction with thrombolytic
therapy.
3) Percutaneous Mechanical Thrombectomy devices
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i) As adjuncts for incomplete thrombolysis
ii) To debulk the thrombus mass before local lysis
B. Surgery
Traumatic acute limb upper limb ischaemia

If the injury involves the first part of the subclavian artery, control may be accomplished with a sternal
split on the right or an anterolateral thoracotomy through the fourth intercostals space on the left.
The axillary artery is best exposed through an infraclavicular incision. Distally, the axillary artery may
be exposed by a medial incision below the Pectoralis Major.
The brachial artery may be approached by a medial curvilinear incision traversing the elbow crease
horizontally.
Interposition grafts with the cephalic or the saphenous veins may be used where primary repair is not
feasible.
Our experience
We‘d like to present our experience of patients with upper limb ischaemia, who reported to us over the
last nine years.
61 cases were seen, comprising 40 males and 21 females. The age range was from 26 years to 70
years.
36 patients presented with symptoms of acute ischaemia of non traumatic origin. 25 patients had
acute ischaemia secondary to trauma (penetrating or blunt).
In patients presenting with acute ischaemic symptoms of non-traumatic origin, the results were
recorded in the immediate post-operative period within 3 weeks and at the end of 3 months. 30 out of
42 patients had palpable pulses at the wrist in the immediate post-operative period. 6 patients
underwent a major amputation as the limb was not salvageable on admission. At the end of 3 weeks
no further limbs were lost, however a palpable pulse at the wrist was found in 21 patients out of the
initial 30. When patients with biphasic signals were also included in this group, the total number
became 25. 18 patients had palpable pulses at their wrists at the end of 3 months, however one more
patient developed an audible doppler signal at the wrist due to improved flow through collaterals.
Discussion
The results of upper limb revascularisation have been reported as variable in different series. Results
of post traumatic vascular repair are considered to be most rewarding with a 90-95% primary patency
rates for the grafts. Autologous vein is the most suitable material for these repairs. Brachial
embolectomy rates were poorer, however with the use of intraoperative thrombolytic agents, the
results can be improved with better flow in the distal part of the limb. An autogenous vein patch
closure of the vessel is considered ideal for the procedure.
Over the years, aspiration, thrombolysis and other non-surgical managements have expanded the
clinician‘s options.
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Pathophysiological basis of acute intestinal obstruction
Dr. S.K. Jain, Amit Gupta
Introduction
A bowel obstruction is a partial or complete blockage in the intestines that prevents it‘s contents from
moving through the intestines normally. Obstruction may occur in the small intestine (small bowel
obstruction) or the large intestines (large bowel obstruction). In severe cases the bowel‘s blood supply
may be cut off. This is called ischemic bowel or bowel strangulation & requires emergency treatment.
Classification & etiology
Bowel obstruction may be classified as –

1. Dynamic - Where peristalsis is working against a mechanical obstruction.
2. Adynamic - This may occur in following forms. Peristalsis
(a) May be absent i.e. Paralytic ileus. Development of this condition is mediated by hormonal
component of sympathadrenal system.
Causes of adynamic ileus are:-
1. After any peritoneal insult.
2. After any abdominal operation.
3. Retroperitoneal haematoma especially associated with vertebral fracture
4. Other retroperitoneal pathology e.g. Ureteric colic, severe pyelonephritis.
5. Thoracic disease i.e. lower lobar pneumonia, fractured rib & myocardial infarction
6. Electrolyte disturbance particularly hypokalemia
(b) It may be present in a non-propulsive form (e.g. mesenteric vascular occlusion or pseudo
obstruction).
(c) Spastic Ileus: - It is very uncommon. There is extreme & prolonged contraction of intestine. It
is seen in heavy metal poisoning, uremia, Porphyria, and extensive intestinal ulceration.
Dynamic Obstruction:-
1. Small bowel obstruction (high or low)
In high small bowel obstruction vomiting occurs early & is profuse . Distension is
minimal.
In low small bowel obstruction Pain is predominant with central abdominal distension
with delayed vomiting.
2. Large bowel obstruction
Intestinal mechanical obstruction can be acute chronic, sub acute, or acute on chronic.
Intestinal obstruction can be simple when blood supply is intact or strangulated when blood supply to
gut is compromised.
Causes of bowel obstruction
Table -
Lesions Intrinsic to the Intestinal Wall
A. Congenital
1. Malrotation
2. Stricture
3. Artesia
B. Infective
a) Tuberculosis
b) Diverticulitis
C.Inflammatory
a)Crohn‘s disease
b) Eosinophilic granuloma
D. Neoplastic
1. Primary neoplasm‘s
a) Benign
b) Malignant
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2. Metastatic neoplasm‘s
3. Peutz-Jeghers syndrome
E. Traumatic
1. Hematoma
2. Ischemic stricture
F. Miscellaneous
1. Intussusceptions
2. Endometriosis
3. Radiation enteropathy or stricture
4. Post ischemic stricture
5. Stricture due to potassium tablets or phenylbutazone
6. Intramural hematoma in patients taking oral anticoagulants
Lesions Extrinsic to the Intestinal Wall
A. Adhesions
1. Postoperative
2. Congenital
3. Post inflammatory
B. Hernia
1. Abdominal wall
2. Intra-abdominal (internal)
a) Congenital, including Para duodenal, foramen of Winslow, diaphragmatic,
mesenteric defect, para-cecal, inter-sigmoid, broad ligament.
Extra luminal causes:-
C. Congenital
1. Annular pancreas
2. Volvulus
3. Persistence of yolk sac
4. Peritoneal encapsulation
D. Neoplastic
1. Carcinomatosis
2. Extra intestinal neoplasm
3. Soft tissue recurrence (e.g., retroperitoneal, mesenteric)
E. Inflammatory
1. Intra-abdominal abscess
2. Starch or foreign body peritonitis
3. Splenosis
F. Miscellaneous
1. Superior mesenteric artery syndrome
2. Cocoon related to peritoneo-venous or ventriculo-peritoneal shunts
Intra-luminal Obstruction
A. Gallstone ileus
B. Enterolith
C. Bezoar
D. Swallowed foreign body
E. Parasites, including tapeworm and Ascaris species
Pathophysiology of bowel obstruction
Absorption and Secretion
Intestinal obstruction has marked effects on intestinal absorption and secretion. Normally, the small
intestine has a tremendous ability to secrete and reabsorb fluid and electrolytes. With mechanical
obstruction, following disturbances are seen (Shields, 1965)
A. Early intestinal obstruction (up to 12hours)
Accumulation of water & electrolytes in lumen due to decreased absorption
B. Between 12 to 24 hours
There is rapid accumulation of intraluminal water & electrolytes due further decrease
in absorption & compensatory increase in intestinal secretion.
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As obstruction persists absorption further decreases & secretion increases. The net
result of this is ;-
i. Intra luminal fluid accumulation leading to proximal intestinal distension
ii. Iso-osmolar volume contraction due to sequestration of fluid in intestinal
lumen
Pathology of increased secretion: - Following theories has been postulated

1. Primary mucosal damage with intra-luminal leakage of plasma & intracellular
fluid
2. Inflammatory changes have been observed proximal to obstruction. Inflammation
leads to secretion of various vaso-active substances i.e. Prostaglandin, serotonin
& histamine. These substances lead to net increase in intestinal fluid secretion.
Increased levels of serum prostaglandin levels have been noted with intestinal
obstruction.
3. Neural dysregulation: - it is mediated by distension induced stimulation of enteric
nervous system. Hexamethonium, a ganglion blocking has been found to abolish
net increase in secretion.
Motility of the Small Intestine
Effects on Motility due intestinal obstruction are as follows:

1. Early in the course of intestinal obstruction contractions of intestine occur with increase in
frequency & intensity in order to overcome point of obstruction. Increased contractile activity is
induced by increase in intrluminal pressure on the day one
2. There are increased migrating clustered contractions proximal to obstruction & are responsible
for abdominal cramps.
Blood Flow
There is a direct relation ship between intestinal distension due to intestinal obstruction & intestinal
blood flow. When the intra-luminal pressure increases to 20 mm of Hg blood is shunted from mucosa
to outer layers & there is reduction of intestinal absorption. At intra-luminal pressure of 30 mm of Hg
capillary blood flow is interrupted & at 60 mm of Hg blood flow is interrupted in small vessels.
Bacteriology
In the absence of obstruction, the jejunum and proximal colon in humans are virtually sterile. A
resident micro flora exists but represents a relatively how concentration (105 to 108 organisms per
millimeter) when compared with bacterial contents in the colon of 109 to 1012 organisms per gram of
stool.
Small bowel obstruction is associated with increased bacterial translocation to mesenteric lymph
nodes even in patients without an intra-abdominal site of infection.
In one series, 59% of patients undergoing laparotomy for intestinal obstruction had positive culture
from the mesenteric lymph nodes, as compared with only 4% of the patients undergoing elective
celiotomy. Escherichia coli were the most common species.
Therefore, with established mechanical small bowel obstruction, preoperative antibiotic prophylaxis is
indicated and peritoneal soiling by spillage of small intestinal content must be avoided.
Systemic Patho physiologic Effects of Intestinal Obstruction

1. Initial isotonic contraction dehydration secondary not only to the intestinal and peritoneal
sequestration of extra-cellular fluid but also to the associated vomiting.
2. Hypokalemia is often present & is due to secretion, and an increase in serum aldosterone
concentration in response to the hypovolemia.
3. Cardiovascular effects:-
a) Tachycardia b) Hypotension secondary to hypovolemia c) Cardiac irritability due to
potassium depletion & increased circulating catecholamines.
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4. Respiratory compromise due to severe abdominal distension & tenting of diaphragms or due to
aspiration of vomitus
5. Prerenal azotemia & acute renal failure in protracted or neglected intestinal obstruction.
5. When strangulation obstruction supervenes all these above effects are magnified Intestinal
infarction may precipitate metabolic acidosis & sepsis associated with vascular collapse
.
Pathophysiology of strangulation obstruction
In strangulation vascular supply to the gut is compromised either by extrinsic pressure (adhesion,
band or hernia orifice) or due to twist of the mesentery. Vascular supply can also be compromised by
closed loop phenomenon, where there is an obstruction of a loop of gut at two points which leads to
progressive distension of gut loop & trans-mural ischemia
Stages in strangulation:-
1. Venous engorgement: - Initially there is venous obstruction which leads to vascular
engorgement, edema & local venous hypertension. This stage is reversible if obstruction is
relieved. This stage does not have any systemic effects.
2. Reflex arterial spasm follows associated with relative tissue anoxia. This stage is also
reversible.
3. If vasospasm persists for long or severe than capillary integrity is lost & areas of intramural
hemorrhage, vascular stasis & vascular thrombosis supervenes. All these changes lead to
further anoxia. If pathology is reversed at this stage there will be formation of stricture also
known as stricture of Garry‘s
4. Mucosal infarction follows & mucosa is sloughed off. Mucosal sloughing begins at the tip of
the intestinal villi & there is a bacterial translocation in to sub mucosa. Events up to this stage
are purely local without major systemic consequences.
5. Trans-mural infarction follows with persistent vascular obstruction & tissue anoxia. Intra
luminal bacteria, bacterial toxins & metabolic products of tissue infarction are released in
peritoneal cavity & systemic circulation even before perforation of gut. Peritoneal fluid at this
stage of strangulation is toxic. Bacterial translocation is responsible for multiple organ
dysfunction
SMALL BOWEL OBSTRUCTION
Clinical Presentation
The four key symptoms that characterize acute mechanical bowel obstruction are
1. Nausea and vomiting,
2. Colicky abdominal pain,
3. Obstipation,
4. Abdominal distention.
The onset of these symptoms varies not only with the duration of established obstruction but also with
the anatomic site of obstruction.
In distal obstructions, the symptoms take time (hours to days) to manifest. Conversely, the more
proximal the obstruction, the earlier and more prominent are the symptoms.
Colicky abdominal pain is usually the cardinal symptom. However, pain may be notably absent in
patients with gastric outlet, duodenal, or high intestinal obstruction. In those patients, nausea and
vomiting may be the only symptoms. In contrast, with more distal intestinal obstruction, the initial and
most prominent symptom is episodic, cramping abdominal pain, this pattern of crampy pain is typically
diffuse, poorly localized, and lasts 30 to 60 seconds; colonic obstruction may have a longer duration
of 1 to 3 minutes. Between spasms, pain resolves completely. These episodes of pain occur
synchronously with borborygmi. In contrast to patients with peritonitis who are hesitant to move and
tend to lie rigidly still patients with colicky pain are restless and change position in an attempt to find
relief; often, the patients double up with pain and are unable to discover a position which gives pain
relief.
Vomiting occurs early in high small bowel obstruction but may be absent or develop late in distal small
bowel or colonic obstruction. At first, the vomitus may contain altered food, but later it becomes bile
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stained. Finally, when the obstruction becomes complete and the dilated obstructed intestine allows
bacteria to proliferate in the stagnant intestinal lumen, the vomitus turns feculent and foul smelling,
indicating a late, established intestinal obstruction. Obviously, in obstruction due to pyloric stenosis,
the vomitus does not become bile stained or feculent.
The onset of obstipation is a late development; indeed, a patient may continue to have bowel
movements and to pass flatus as the distal, unobstructed intestine empties. Only late does the
obstipation become complete. Moreover, patients with partial or incomplete bowel obstruction may
continue to pass flatus and diarrhea intermittently; explosive bouts of diarrhea with sudden relief of
pain are not uncommon.
Abdominal distention develops progressively later in the course of the obstruction as the proximal
intestine becomes progressively dilated (recall that the intestinal tract normally secretes and
reabsorbs 6 to 10 liters of fluid per day; a small shift of that equilibrium causes fluid to accumulate
quickly within the bowel lumen). Abdominal distention is prominent in midgut and high-gut
obstructions and is usually absent in patients with gastric outlet, duodenal, or high intestinal
obstruction. One exception might be the patient with chronic gastric outlet obstruction, a markedly
dilated stomach, and a characteristic upper abdominal distention.
Although these symptoms are characteristic of mechanical intestinal obstruction and can be helpful in
the differential diagnosis, various exceptions do occur. For example, with closed-loop obstruction or
with incarceration of intestine in a hernia orifice, relentless reflex vomiting may be the initial symptom
and occurs early in the course. This represents an abdominal reflex related to acute, unrelieved
intestinal distention and irritation. Moreover, these patients may experience a constant, visceral pain
rather than a crampy, colicky pattern.
Physical Examination
1. Patients usually appear ill with paroxysms of obvious colicky abdominal discomfort.
2. General physical examination often reveals the signs of dehydration.
3. Tachycardia and hypotension may indicate severe dehydration, peritonitis, or both. 4. 4.Fever
suggests the possibility of strangulation or some other complication of the underlying process.
5. The abdomen is usually distended. The degree of distention varies both with duration and
location of the obstruction.
6. Peristaltic waves characteristic of small bowel obstruction are sometimes visible through the
abdominal wall of thin patients with a distal mechanical small bowel obstruction
7. Surgical scars should be noted because of the etiologic implication .
8. Abdominal auscultation in patients with intestinal obstruction usually reveals periods of
increasing or crescendo bowel sounds with the abnormal bowel borborygmi of tinkles. With
late, neglected obstruction, as the proximal intestine dilates, it loses its contractile activity and
rushes may be absent. In this situation, a late mechanical bowel obstruction is often difficult to
differentiate from adynamic ileus on clinical grounds alone. A patient with an early duodenal
or proximal jejunal obstruction may have normal bowel sounds. A reliable physical finding is
the gastric succession splash; when present more than 2 to 3 hours after the last meal, a
positive succession splash is strong evidence of a gastrointestinal obstruction, either
mechanical or function.
9. On palpation of the abdomen, the examiner commonly can appreciate distended loops of
intestine with a more established chronic obstruction. Peritoneal signs (such as localized
tenderness, rebound, and guarding) should alert the examiner to reconsider the diagnosis of
intestinal obstruction or to entertain the likelihood of strangulation obstruction. An orderly
search of all the possible hernial orifices should also be performed as well as an examination
for abdominal masses (neoplasm, intussusception, abscess). The danger of overlooking a
small groin hernia, particularly a femoral hernia in obese patients or the unusual obturator
hernia, cannot be overemphasized. The hernia may produce little local pain or tenderness,
and central abdominal colic tends to focus attention away from the causative lesion.
!0.Digital rectal examination is essential. Fecal impaction is a frequent cause of obstruction in
elderly and immobile patients, institutionalized psychiatric adults, and children with a mental
handicap. An obstruction low rectal cancer may be palpable. A mass in the recto-vesical
pouch suggests widespread intra-peritoneal neoplasia. Moreover, the presence of feces
should be noted, and they should be examined for occult blood. Hematochezia suggests a
mucosal lesion as may occur with cancer, intussusceptions, or strangulation infarction.
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Proctoscopy and sigmoidoscopy can reveal the cause of distal large bowel obstruction. In the
case of sigmoid volvulus, sigmoidoscopy may be also therapeutic.
Laboratory tests
Routine investigation
Hemoglobin, Total & differential leukocyte count. Increased total leukocyte count with shift to right
suggest strangulation
Blood Urea estimation to rule out renal failure
Serum electrolytes estimation
Arterial Blood Gas analysis
CPK (MM band) estimation: - Increased levels points towards strangulation
Radiographs and Imaging
The role of imaging studies is primarily to confirm the diagnosis of bowel obstruction and exclude
other potential diagnoses (e.g., perforated viscus). Other uses are to help locate the site of obstruction
and provide information about the lesion responsible for the obstruction.
Plain Films
On plain films supine and upright radiographs of the abdomen, the cardinal findings that suggest
the diagnosis of small bowel obstruction reflect the accumulation of air and fluid proximal to the
point of obstruction and clearance or absence of fluid and air distal to the obstruction. Such
findings include dilated loops of small intestine on the supine radiograph and multiple air-fluid
levels, which often layer out in a stepwise manner on erect radiographs or lateral decubitus film.
In general, dilated loops of small intestine are defined as those larger than 3 cm in diameter. The
proximal colon is considered dilated when the diameter reaches 8 to 10 cm and the sigmoid
colon, 4 to 5 cm.
With more distal-based intestinal obstruction, one can usually identify a distended small or large
intestine. Gas in the small bowel outlines the valvulae conniventes, which usually occupy the
entire transverse diameter of the bowel image. In contrast, the colonic haustral marking occupy
only a portion of the transverse diameter of the bowel typically, the small bowel pattern occupies
the more central portions of the abdomen, whereas the colonic shadow is on the periphery of the
abdominal film or in the pelvis. Depending on the duration of the obstruction, the portions of small
and large gut devoid of air or feces, however, air or feces may still be present in the unobstructed
distal intestine, especially early in the course of the illness or with partial or intermittent
obstruction.
Occasionally, abdominal radiographs not only confirm the clinical suspicion of intestinal
obstruction but also reveal the cause. The plain radiographs may show air in the biliary tree
(pneumobilia) indicative of a biliary-enteric fistula; when small bowel obstruction coexists, this
spectrum of findings in almost pathoganomonic of gallstone ileus even in the absence of any sign
of the obstructing gallstone.
A closed-loop obstruction of the small intestine may contain fluid with very little gas, and thus it
may not be visible or only barely visible as a minimally dilated sentinel loop that remains
unchanged in position on films that are performed in different projections. Free air suggests
perforation of a viscous and virtually mandates immediate operation in the patient with findings of
mechanical intestinal obstruction.
Computed Tomography
The obstructing segment can usually be localized and characterized as complete or incomplete.
CT allows imaging of the abdominal contents outside the lumen. & because of this advantage, the
nature of the obstruction, especially when secondary to an extra luminal or liver metastases,
ascites, and solid-organ parenchyma abnormalities, can often be identified, thereby helping to
define the cause of the obstruction.
With CT, preoperative detection of strangulation obstruction and primary mesenteric ischemia
may be improved.
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Management
In most patients, prompt diagnosis and operation are essential to reduce the risk for strangulation. A
common saying is, ―The sun should never rise and set on a (complete) small bowel obstruction. Initial
management involves fluid resuscitation, nasogastric decompression, and preparation for possible
operation. After serum electrolyte levels are checked and blood is cross-matched, vigorous
rehydration with an isotonic sodium chloride solution should be guided by central venous pressure or
pulmonary artery pressure monitoring in elderly patients and patients with cardiopulmonary co-
morbidity, urine output, and, when indicated, by arterial blood gas values. Strong consideration should
be given to placing an indwelling urinary catheter and central venous catheter in older patients to aid
in monitoring the success of resuscitation. After the patient has begun adequate urine output,
potassium chloride should be added to the infusion; chronic vomiting can deplete potassium stores.
Naso-gastric decompression empties the stomach, reduces the risk for aspiration, and minimizes
further intestinal distention by swallowed air. However, a naso-gastric tube is often not effective in
decompressing distended intestine distal to the ligament of Treitz. The use of longer tubes has been
advocated in certain settings in which early operation is unappealing, such as in patients with partial
obstruction arising from Crohn‘s disease, peritoneal carcinomatosis, radiation enteropathy, or many
previous laparotomies for obstruction. This approach is based on the concept that the long
nasointestinal tube migrates into the small bowel distal to the ligament of Treitz and, because there
are no valves or areas of functional obstruction distal to the ligament of Treitz, a more effective
jejunoileal decompression occurs, perhaps allowing (nonoperative) relief of the obstruction. Although
this concept is appealing, there appears to be no good, objective evidence to support the use of long
tubes in such settings.
If marked hemo-concentration and severe electrolyte imbalance were present initially laboratory
studies should be repeated before operation to be certain that serious deficiencies (e.g., hypokalemia)
have been corrected. When the values return toward normal, the patient can undergo operation.
Operation should be considered after pulse, blood pressure, central venous pressure, and urinary
output become normal or if presumed underlying strangulation is causing persistent hemodynamic
instability and an adequate resuscitation has ensued. After the decision to proceed with an operation
is made, the patient should be given prophylactic, broad-spectrum antibiotics covering gram-negative
aerobes and anaerobes (particularly if strangulation is suspected) to minimize infective complications
if resection proves necessary or peritoneal spillage occurs as the result of an unintentional
enterotomy. In patients being obsweved, antibiotics are controversial and are of questionable value;
they can obscure an underlying process and delay optimal therapy.
The timing of operation depends of three primary factors: duration of obstruction, that is, severity of
fluid, electrolyte, and acid-base abnormalities; the opportunity to improve vital organ function; and
consideration of the risk for strangulation. The mortality rate from obstruction with irreversible
ischemia (gangrene) ranges from 5 to 31%, whereas with simple mechanical obstruction relieved
within 24 hours, the mortality rate is about 10%. Because no test reliably detects strangulation
preoperatively (see earlier), operation should be performed as soon as is reasonable, but not before
adequate resuscitation. When the diagnosis of bowel obstruction is likely or certain, indications for
surgery include the following:
1. Rapidly progressing constant, non-crampy abdominal pain or distention, with or without

peritoneal findings.
2. Development of peritoneal findings, fever, tachycardia, diminished urinary output,
leukocytosis, hyperamylasemia, and metabolic acidosis
3. Failure of an obstructive picture of complete obstruction to resolve within 12 to 24 hours,
even in the absence of evolving symptoms of peritoneal findings
4. Large bowel obstruction
After the diagnosis of complete small bowel obstruction is made, whether simple or strangulated,
celiotomy should proceed without undue delay. It is reasonable to commit the patient to a variable
period of observation if the diagnosis is uncertain, if there is a possibility of a nonsurgical diagnosis, or
if the obstruction is partial and not complete. Several studies have shown that most patients (70 to
80%) with adhesive partial obstruction of the small bowel had resolution with nasogastric suction, and
most patients so treated responded within 24 hours.
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Operative Treatment
In general, the nature of the problem determines the approach to management of intestinal
obstruction. The choice of incision can be important. In simple obstruction, such as an incarcerated
inguinal hernia, operative reduction and repair of the hernia through the same incision (either inguinal
or a preperitonal approach) usually suffices. When obstruction develops in the early postoperative
period, the original incision is best reopened. In the absence of external hernia, and if the patient has
no previous abdominal surgery or has more distant previous abdominal surgery it is better to use a
midline incision because it affords maximal exposure to all quardrants of the abdominal cavity. The
obstructed point can be identified by following the distended bowel distally to find collapsed intestine.
Careful manual decompression of the obstructed intestine proximally past the ligament of Treitz and
into the stomach makes the operative manipulation easier. A separate proximal enterotomy to
introduces a catheter or suction device for intraluminal decompression is rarely indicated because of
the risk for peritoneal contamination by spilled intestinal content.
Adequate therapy involves careful release of the obstruction. Extreme care is necessary when
handling the acutely distended, inflamed, thin-walled intestine. Moreover, at the actual point of
obstruction, strangulation with transmural infarction may have occurred. Undue trauma or tension may
lead to bowel rupture and intra-abdominal contamination with the bacteria-laden enteric contents of
the obstructed intestine. Obstruction caused by peritoneal adhesions should be relieved by division of
the adhesions. In operating on patients with multiple intraabdominal adhesions, the surgeon should
verify that no additional sites of obstruction or bowel wall compromise remain distal to the clinically
obvious point of obstruction. This concept is especially important when there is two separate areas of
the obstructed loop would have volvulated around the band, and each area should be inspected.
If the obstruction is caused by a hernia, the herniated content is reduced and the defect obliterated. A
unique situation exists when a complex abdominal wall hernia that may not lend itself to repair
actually has caused the intestinal obstruction. In this unusual situation, correction of the site of
obstruction is obviously indicated, and a wide unroofing of the hernia defect, thereby obliterating all
small defect (―Swiss cheese hernia‖) and consolidating all the small defects into one large
unobstructing hernia may be indicated.
A different approach to selected obstructing lesions is to create an intestinal bypass, as, for example,
in the treatment of a complex matted area of distal irradiated ileum by a proximal ileotransverse colon
anastomosis. Such a bypass, leaving areas of obstructed intestine in situ, should be carefully
considered; bypass of severely matted radiation enteropathy or obstruction from unresectable
malignancy is often warranted, but bypassing Crohn‘s disease may predispose the patient to
development of the malignancy or to further consequences of a ―blind-loop‖ syndrome. Similarly, the
rare patient with a distal ileal carcinoid may have an intense mesenteric fibrosing reaction causing
bowel obstruction. Strong consideration should be given to resecting this area, even when known
gross local or distant disease is left behind, because as this ischemic fibrosing process continues, the
bowel may become irreversibly ischemic and perforate.
It is often difficult to determine whether a segment of strangulated bowel is viable after relief of the
strangulation. The criteria generally used in determining bowel viability are color, ability to contract,
and arterial pulsation. If intestinal viability is questionable, the bowel segment should be released of
the obstruction and placed in a saline-moistened sponge for 15 to 20 minutes and then ex-examined.
If normal color has returned and peristalsis is evident, it is usually safe to retain the bowel. If there is
reasonable doubt about its viability, the bowel probably should be respected or a second-look
procedure planned to be performed 12 to 24 hours later. The decision to perform a second-look
procedure is made intraoperatively and should be acknowledge as such postoperatively.
Many other aids to the diagnosis of irreversible ischemia of a bowel segment have been described.
Used of Doppler technology to determine the presence of arterial pulsation both in the mesentery and
in the anti mesenteric aspect of the bowel wall can help; loss of anti mesenteric arterial pulsations
questions viability. Similarly, intravenous injection of fluorescent dye with subsequent illumination of
the bowel wall with a Wood‘s light should show a uniform fluorescence indicative of vascular
perfusion. Loss of fluorescence signifies irreversible and warrants either resection or a second-lock
procedure. A recently described device, the electronic contractility meter, which monitors the ability of
the bowel to contract, is as yet of unproven worth.
297
With massively distended intestine, closure is facilitated by intestinal decompression. Bowel
decompression can be accomplished through a long intestinal tube passed Trans
Orally or trans nasally. With manual guidance through the pylorus and the duodenum, the tube can be
through the pylorus and the duodenum; the tube can be manipulated into the jejunum. The fastest and
safest method, however, involves manual, retrograde milking of fluid back into the stomach; the
anesthesiologist can then aspirate the enteric fluid through the nasogastric tube. Controlled
enterotomy with intubation for intestinal decompression is another option, but it necessitates
enterotomy and potential intra peritoneal contamination and is not preferred. The used of retention
sutures seems prudent in the presence of malnutrition, malignant disease, old age, chronic lung
disease, and the need of drugs that affect wound healing (e.g., steroids)
Role of Laparoscopy in the Management of Bowel Obstruction
Today, laparoscopy is being applied to a number of obstructing small bowel and colonic processes,
such as relief of small bowel obstruction secondary to adhesions or incarcerated hernias, foreign body
causing intestinal obstruction, resection for appendicitis or a Meckel‘s diverticulum causing intestinal
obstruction, and evaluation and resection for inflammatory bowel disease (i.e., Crohn‘s disease).
Laparoscopic treatment of small bowel obstruction can be successful, leads to a shorter hospital stay
and quicker rehabilitation of the patient, and has good long-term results. The operation can be
completed laparoscopicaly in most patients (70 to 87%). Moreover, laparoscopy can determine the
disease process in almost all patients. With further experience, laparoscopic exploration is an
excellent diagnostic modality in acute small bowel obstruction and may allow a fully laparoscopic
adhesiolysis with relief of the intestinal obstruction in many of these patients. The best results appear
to be in those patients with either a non resolving partial small bowel obstruction or early acute small
bowel obstruction before the abdomen becomes markedly distended.
Interestingly, small bowel obstruction after previous laparoscopy may be due to small bowel
incarceration in a peritoneal defect created by trocar placement. A prompt operative intervention is
recommended for this specific complication of laparoscopic surgery.
References
1. Abrams, G.D.: Impact of the intestinal micro flora on intestinal structure and function. In Hentges, D.J. (ed.):
Human Intestinal Micro flora in Health and Disease. New York, Academic Press.
2. Anderson, C.A. and Humphrey, W.T.: Contract radiography in small bowel obstruction: a prospective, randomized
trial. Milit Med. 1997.
3. Antoncic, R.F., and Lawson, H.: The muscular activity of small intestine in the dog, during active obstruction.
Ann. Surg., 1998.
4. Halthazar, E.J., Liebeskind, M.E., nd macari, M.: Intestinal ischemia in patients in whom small bowel obstruction is
suspected: Evaluation of accuracy, limitations, and clinical implications of CT in diagnosis. Radiology, 2000.
5. Bass, K.N., Jones, B., and Bulkley, G.B.: Current management of small-bowel obstruction. In Cameron, J.L (ed):
Advances in Surgery, vol 31, Chap. I. St. Louis, Mosby-Year Book 1998, pp. 1-34
6. Basson, M.D., Fielding, L.P., Bilchik, A.J., et al.: Does vasoactive intestinal polypeptide mediate the
pathophysiology of bowel obstruction? Am. J. Surg. 2002
7. S.R., Coeh, S.M., Wexner, S.D., and Nogueras, J.J.: Must early postoperative intake be limited to laparoscopy?
Dis. Colon Rectum, 37:584, 1994
8. Boley, S.J., and Veith, F.J.: Effects of bowel distention on intestinal blood flow. In Boly, S.J. (ed.): Vascular
Disorders of the Intestine. New York, Appleton-Century-Cropfts, 1971, P. 429.
9. Deitch, E.A., Bridges, W.M., Ma, J.W., et al.: Obstructed intestine s a reservoir for systemic infection. Am. J. Surg.,
159(4):394-401, 1990
10. Donckier, V., Closset, Van Gansbeke, D., et al.: Contricution of computed tomography to decsion making in the
management of adhesive small bowel obstruction. Br. J. Surg., 85:1071-1074. 1998.
11. Franklin, M.E., and Dorman, J.: Laparoscopic surgery in acute small bowel obstruction. Surg. Laparosc. Endosc.
4:289-296. 1994.
12. Kong, S.E., Blennerhaset, L.R., Heel, K.A., et al.: Ischaemia reperfusion injury to the intestine. Aust. N.Z.J. surg.,
68(8):554-561, 1998.
13. Reinser, R.M., and Cohern, J.R.: Gallstone ileus: A review of 1001 reported cases. Am Surg., 60:441-446, 1194.
14. Sewell, H.F., and Wakelin, D.: Intra-abdominal sepsis: An immuno cytochemical study of the small intestine
mucosa. J. Clin. Pathol, 50(4):294-298, 1997.
15. Shikata, J., Shida, T., Amino, K., and Ishoka, K.: Experimental studies on the hemodynamics of the small intestine
following increased intraluminal pressure. Surg. Gynecol. Obstet. 156:155, 1983.
16. Thompson,J.: Pathogenesis and prevention of adhesion formation. Dig. Surg., 15:153-157. 1998.
17. Wiebke, E.A.: Malignant gastrointestinal obstruction, In Lefor, A.T. (ed): Surgical Problems affecting the patient
with Cancer. Philadelphia, Lippincott-Raven, 1996, pp. 25-60.
298
Anorectal malformations (Imperforate anus)
Dr Satish Aggarwal
Anorectal malformations comprise a SPECTRUM of congenital malformations in which the anus fails
to open normally on to the perineum. At one end are ―low‖ malformations where the anal canal is
present but covered by perineal skin or there is a perineal opening discharging meconium (perineal
fistula). These are easy to treat by a single perineal operation without the need for a colostomy. At the
other end of the spectrum are severe (or high) malformations where the rectum ends at or above the
pelvic floor muscle and communicates with the genitor-urinary tract; associated malformations are
frequent and treatment is more complex- a colostomy is usually needed at birth as initial
management.
The malformations occur with a multifactorial aetiology. The embryological basis for ―high‖
malformations is the failure of the urorectal septum to develop resulting in a recto-urinary fistula in
males and recto vaginal fistula in girls. Mesodermal failure at the perineal mound is responsible for
―low‖ lesions.
Classification
Anatomical Classification is based on the level of termination of the rectum in relation to the levator
ani (pelvic floor). The pelvic floor is like a funnel. Following malformation types can occur:
High: Rectum ends above the levator. (Supralevator)

Intermediate: Rectum ends within the funnel of the levator.
Low: Rectum ends below the levator. (Translevator)
The typical malformations in males are:
High: Recto vesical fistula. Recto prostatic fistula

Intermediate: Recto-bulbar fistula
Low: perineal fistula, covered anus, anal stenosis, bucket handle anomaly
Typical female defects are:
High: recto vaginal fistula

Intermediate: Recto-low vaginal fistula, Recto-vestibular fistula
Low: Ano vestibular fistula, anterior ectopic anus.
Functional classification:
Alberto Pena proposed a functional classification that is much simpler and is aimed at decision
making in management. According to this the anomalies are divided into two groups:
1. Rectum ending within 1 cm of the skin: Suitable for primary perineal operation to
create neo anus. No colostomy needed.
2. Rectum ending more than 1 cm from the skin: Initial colostomy followed by definitive
pull through at 6-8 weeks
According to Pena, in 80% patients the decision for colostomy or primary perineal operation can be
taken on the basis of clinical features and the appearance of the perineum. In the rest a prone cross
table lateral film is required to determine the distance of the rectal pouch from the skin. In these cases
the above classification comes handy to take a decision.
Anatomy of sphincters in anorectal malformations:
The muscular component of continence is formed by levator ani, specially the lower most fibres (also
called as pubo-rectalis sling). Further there are the so called subcutaneous and superficial external
sphincters that surround the rectum and the anal canal. During an operation however, it is not
possible to identify the different components of the external sphincter. Surgically, there is a continuum
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of vertically oriented striated muscle fibres from the skin at the anal dimple to the lowermost fibres of
levator ani. A mid sagittal incision would bisect these fibres into right and left halves. This is referred
to as ―striated muscle complex‖. Aim of surgery is to bring the rectum through the centre of muscle
complex in order to restore the sphincter mechanism. Surrounding the vertical fibres on either side are
para-saggital fibres that lie horizontally and run from the perineal body in front to the skin behind the
anal dimple. The sphincters are well developed in low malformations but are poor in high
malformations.
Incidence: 1 in 5000 (similar incidence for TOF and HD)
Male: female: 3: 2
Associated malformations:
Incidence: 50-60%
60% are genitor-urinary, 25% vertebral, 20% cardiac, 10% GI
15% have VACTERL / CHARGE association.
Severer the anorectal malformation the higher the incidence of associated malformations
Two most important aspects in the initial management are:
1. Is the case suitable for a primary perineal anoplasty without a colostomy or an initial
colostomy followed by delayed repair is more appropriate?
(Best decided at 24 hours of age)
2. Is there any other life threatening association that needs more urgent attention – e.g. tracheo-
esophageal fistula, severe cardiac malformation? Therefore, always pass a nasogastric to
rule out oesophageal atresia and leave it for gastric decompression.
Clinical features and pathological anatomy
The topic is discussed separately in boys and girls.
Males:
Absent anus at birth.
Examine perineum: look for gluteal fold, natal cleft, and palpate spine/sacrum. Is it a flat bottom? Is
there a dimple at the anal site with pigmentation? Is ano-cutaneous reflex present? Is there a fold of
skin under which you can pass a probe (Bucket handle deformity), is there any mass?, can you see a
thin white epithelial thickening in the median raphe – suggests anocutaneous fistula, is there any
speck of meconium in the perineum – perineal fistula.
Is there any abnormality of the external genitalia – bifid scrotum, hypospadias, and undescended
testes? Look for evidence of meconuria – gas or meconium discharge per urethra.
Important: The exact level of anomaly may not be evident at birth because it takes time for the
ingested air to reach the rectum. Sufficient intra abdominal pressure builds up in about 24 hours to
overcome the resistance of the pelvic floor, so that meconium or air could force through a fistula.
If within 24 hours you can see meconium on the perineum – low anomaly. Go for perineal anoplasty.
No need for colostomy.
If meconium or gas passed per urethra at any stage – indicates high anomaly. Go for colostomy.
Prone Cross table lateral shoot abdominal film (If clinical information at 24 hrs insufficient to
decide if a colostomy is needed).
Technique:
Place a radio-opaque marker at the anal site.
Prone position with pelvis elevated – leave in this position for 5 minutes before taking the x-
ray (to allow gas to layer on the meconium)
Dead lateral view centring over the greater trochanter.
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Interpretation:
See distance of rectal gas from the marker (take care of magnification).
< 1cm: Suitable for primary repair
> 1cm: Colostomy needed.
.
Indicators of “high” anomaly (colostomy indicated):
No meconium in the perineum
Flat bottom, absent anal dimple/pigmentation, absent anocutaneous reflex,
Sacral abnormality (or on X-ray)
Meconium in urine (or gas in bladder on x ray)
Suggestion of a pouch colon on X ray (>50% of transverse span)
Associated bifid scrotum, proximal hypospadias, bilateral undescended testes
Indications of low anomaly (suitable for primary anoplasty):

Good perineum, pigmented dimple, anocutaneous reflex
Visible fistula in the perineum
Bucket handle deformity – a bridge of skin over the anal site under which an instrument can be
passed and meconium can be seen under the skin.
Final decision will depend on many other factors: birth weight, maturity, and other malformations. It is
safer to open a colostomy in doubtful cases.
Females:
Most anomalies are low. Look for the number of openings in the vulva/ perineum
3 openings: Ano-vestibular fistula (Commonest), recto-vestibular fistula, perineal fistula, anterior

ectopic anus
2 openings: Recto-vaginal fistula. (Rarely vestibular fistula with vaginal atresia).
1 opening: Common Cloaca
Examine in good light keeping the legs apart. The vestibular opening is usually very small and may be
hidden within the posterior fourchette. When probed the catheter may go posteriorly (ano-vestibular
fistula) or superiorly (rectovestibular fistula). This differentiation may be very subtle but is important in
that rectovestibular fistula will almost certainly require a colostomy while ano-vestibular fistula could
be repaired primarily.
Colostomy or primary Mini PSARP?
Common cloaca and rectovaginal fistula always require a colostomy. Claoca will also need
emergency evaluation (US) for obstructive uropathy and distended vagina – and often needs
vesicostomy / vaginostomy in the same sitting.
When there are three openings in the vulva the decision is more of individual surgeon‘s choice. The
safest option would be to do a colostomy. However, it is not a dire emergency as the gut is getting
decompressed, which may be aided by calibration of the opening or gentle dilatation with Hegar
dilators. The options should be discussed with parents. While primary repair is definitive saves the
child from a stoma, there is a higher risk of wound breakdown / infection leading to impaired
continence, anal stenosis and need for redo surgery. The author‘s current approach for ano-vestibular
fistula is a primary PSARP at few weeks of age.
Surgery (colostomy or primary repair) may be carried out as a planned acute within the first few days.
If the child develops abdominal distension or decompression is not adequate, early colostomy is
indicated.
Remember: if in doubt do a colostomy.
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Colostomy:
High divided sigmoid / descending colostomy is performed through an oblique incision in the left iliac
fossa. Leave good skin bridge between the active stoma and the mucus fistula to facilitate application
of stoma bag. .
For cloaca – Transverse divided colostomy (distal colon may be needed for vaginal reconstruction)
Sigmoid/descending colostomy is easy to manage as the effluent is well formed, fluid loss and skin
excoriation is less, and it is easy to do a distal washout. The incidence of prolapse is low. Patients
with large recto urinary fistula may leak urine into the distal colon. With sigmoid colostomy there is
less chance of hyperchloremic acidosis as the urine comes out through the mucus fistula without
getting absorbed significantly. Moreover, performing a distal cologram is easier and more informative.
Pitfalls in colostomy
Transverse sigmoidostomy: While intending to perform a right transverse colostomy, a distended

sigmoid loop reaching the right hypochondrium is mistaken fro transverse colon and a stoma is
created. This puts the distal limb on traction and does not leave scope for mobilisation during
definitive pull through operation. Distal cologram will diagnose this accurately. Colostomy transplant at
left iliac site is needed before considering a pull through.
Too low colostomy: This is the commonest mistake. The apex of the sigmoid loop is brought out as
a stoma leaving small length distally. The best way to prevent this is to identify the fixed portion of
colon i.e. distal descending colon and then come down along the sigmoid colon and form a stoma at a
level that comes on the surface without tension. This will leave most of sigmoid distal to the stoma,
which can be used fro mobilisation during pull through operation.
Loop colostomy: A loop colostomy is less likely to divert completely. Faecal contamination of the
distal limb may cause repeated urinary infections through a fistula, can cause feculomas, and
jeopardise the pull though by infective complications.
Twisted colostomy: The distally situated stoma brings out faeces while the proximally situated stoma
acts as a mucus fistula. This is a technical mistake during surgery and is of no major consequences
provided the mother gives pre-operative washouts through the mucus fistula only. The author has
seen ―distal washouts‖ being given through the active stoma because the active stoma was the distal
stoma.
Further investigations during initial admission:
Renal and Spinal Ultrasound: to look for renal malformations, tethered cord
Echocardiography
Chest and spine Xray
Sacral Pena ratio
Chromosomal analysis
US spine – MRI if US abnormal
Post op after colostomy

Distal loop washout with saline from day 5. Daily until clear, then weekly
Measure stoma output (if >20ml/kg/day start loperamide)
Monitor urinary sodium (if <10mmol/l – add supplement to maintain at >10-40 mmol/l)
Prophylactic trimethoprim 2 mg/kg nocte
MCUG / distal loopogram at 4-6 weeks (cover with antibiotics; no cardiac anomaly: iv
gentamycin 2 mg/kg; cardiac anomaly: iv gent + iv amoxicillin (250 mg) followed by oral
amoxyl 125 mg 6 hrs later. (If allergic to Penicillin- iv clindamycin (75mg) followed by oral
clindamycin (37.5 mg) six hours later.
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Post Discharge pre PSARP
Weekly distal washout, monitor weight, urinary sodium, increase trimethoprim as per weight,
parental support for stoma care.
Definitive Repair (PSARP – Posterior Sagittal Ano Recto Plasty) is performed at 8-12 weeks.
Pre-op Distal washouts a day before or until clear

Check distal loopogram available.
Antibiotic on induction.
Consent
Operation in boys:
Under general endotracheal anaesthesia, bladder is catheterised. The patient is placed in prone jack
knife position. Buttocks are spread apart with elastic adhesive tape on each side. A mid sagittal
incision is placed from mid sacrum to just anterior to the anal dimple. Keeping in midline the incision is
deepened. The muscle complex and the parasagittal fibres are identified and confirmed with muscle
stimulator. The coccyx may need bisection or division to access the rectal pouch... The levator ani is
divided in midline. Endopelvic fascia is divided to identify the rectal pouch. The pouch is opened in
midline between stay sutures and the fistula identified at the lower end of the pouch. The fistula is
closed from within with a purse string fine vicryl or PDS suture. The anterior dissection immediately
above the fistula is performed in the submucosal plane to prevent damage to the urethra. At about 2
cm from the fistula, the rectum can be mobilised full thickness all around. It is mobilised as much as is
needed to bring it down to the site of neo anus, which should be marked in the beginning of the
operation at the anterior and the posterior limit of the striated muscle complex. The levator is closed
behind the rectum. The rectum is then brought in the centre of the muscle complex and anoplasty is
performed by muco cutaneous anastomosis at the marked site of anus.
If the anomaly is very high and the rectal pouch can not be reached from below, a 28 size chest tube
is placed in the centre of muscle complex and the muscle closure is done around the tube as if the
tube is the rectum. The patient is then turned and a laparotomy performed to identify the rectal pouch
and rectovesical fistula. After the fistula is taken down, the rectum is tacked to the tube passed from
below. The tube is then gently pulled in the perineum bringing the rectal pouch at the skin where a
muco cutaneous anastomosis is performed.
Operation for ano vestibular fistula in girls:

The position and anaesthesia are the same. Bladder is catheterised after positioning the patient.
Incision is from mid sacrum to the posterior fourchette. Muscle complex is divided in the midline. The
vestibular fistula is held in multiple stay sutures and a circumferential incision is made around it
separating it from vagina in front. The key step is separating the rectum from vagina. They are
intimately adherent and share a common wall for varying lengths, less in ano vestibular and more in
recto vestibular fistula. Once sufficiently mobilised, the perineal body is reconstructed, location of neo
anus is decide as in boys. Anoplasty is performed and wound closed.
Post-op If no laparotomy – feed 6-12 hrs later

Urinary catheter for 5 days.
Triple antibiotics for 48 hrs, then treatment dose Cephalexin/ trimethoprim until
catheter comes out, then prophylactic until VUR ruled out.
Nil PR for 14 days.
Dilatation to start at 14 days.
Closure of colostomy:
Performed once anal dilatation to adequate size achieved.
Continue dilatations until closure.
Skin preparation – dermagard wipes 3/day. May use barrier applications {Adapt
(Hollister), stomahesive (Squibb)}
Continue dilatation post op for 4-6 weeks.
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Regimen for anal dilatation post anoplasty
Use Hegar dilators.

First dilatation at 14 days (10 for low malformations)
First begin with size 8
Increase by one size per fortnight
e.g. 7/8 twice a day for 1 week
8 twice a day for 1 week
8/9 twice a day for 1 week
……
12 twice a day for 1 week
12 once a day for 1 week
See consultant when achieved desired dilatation as ready for closure.

Usual time taken to achieve target is three months.
Normal size for age:

1-4 months Hegar 12
5-8 months Hegar 13
9-12 months Hegar 14
13 months + Hegar 16
Post colostomy closure:

Restart dilatations BD at the size stated in op notes
Decrease to daily after one month
Decrease to twice weekly after one month
Decrease to weekly after one month
Stop after a month
CONTROVERSIAL ISSUES
Primary PSARP for ―high‖ malformations in males:
Some surgeons favour primary PSARP without a covering colostomy in selected cases of recto bulbar
fistula. It is a shade better than the standard approach of colostomy followed by PSARP in that the
sensory stimulation for maturation of anorectal continence mechanism is established immediately
after birth, which should lead to better continence mechanism. However, the downside is that the
anatomy is uncertain because the level of fistula has not been ascertained pre-operatively.
Consequently the ―blind‖ perineal exploration increases the risk of damage to urethra, seminal
vesicles, and ureters. Also the operation is technically demanding.
Laparoscopic repair of ARM
Laparoscopic approach has been successfully used to perform / aid repair. Colostomy is opened at
birth. Laparoscopic assisted pull through can be performed at about three months age. The
colorectum in the pelvis is mobilised laparoscopically and the fistula taken down. The urethral end of
the fistula is closed with an endo-loop. The site of anus is decided by identifying the stratified muscle
complex by using a muscle stimulator. A small midline incision is made in the centre of this site and a
10 mm trocar introduced in the pelvis. The mobilised rectum is pulled down through the port and
anastomosed to the skin.
The advantages of laparoscopic approach are clear visualisation of fistula in the deep pelvis,
magnification and accuracy. There is, however, limited experience and long term data is lacking.
Anterior Sagittal Anorectpoplsty (ASARP) in females
Some surgeons perform the pull through operation in females in lithotomy position using the anterior
approach. The operation is essentially the same as the more frequently used posterior approach. The
author has no experience with this approach.
304
References
1. deVries PA, Pena A. Posterior sagittal anorectoplasty. J Pediatr Surg. Oct 1982;17(5):638-43.
2. Hong AR, Acuna MF, Pena A, et al. Urologic injuries associated with repair of anorectal malformations in male
patients. J Pediatr Surg. Mar 2002;37(3):339-44.
3. Parrott TS. Urologic implications of anorectal malformations. Urol Clin North Am. Feb 1985;12(1):13-21.
4. Pena A. Anorectal malformations. Semin Pediatr Surg. Feb 1995;4(1):35-47.
5. Pena A. Current management of anorectal anomalies. Surg Clin North Am. Dec 1992;72(6):1393-416.
6. Pena A. Management of anorectal malformations during the newborn period. World J Surg. May-
Jun 1993;17(3):385-92.
7. Pena A. Posterior sagittal approach for the correction of anorectal malformations. Adv Surg. 1986;19:69-100.
8. Pena A, Devries PA. Posterior sagittal anorectoplasty: important technical considerations and new applications. J
Pediatr Surg. Dec 1982;17(6):796-811.
9. Pena A, Hong A. Advances in the management of anorectal malformations. Am J Surg. 2000;180(5):370-6.
10. Pena A, Migotto-Krieger M, Levitt MA. Colostomy in anorectal malformations: a procedure with serious but
preventable complications. J Pediatr Surg. Apr 2006;41(4):748-56; discussion 748-56.
11. Shaul DB, Harrison EA. Classification of anorectal malformations--initial approach, diagnostic tests, and
colostomy. Semin Pediatr Surg. Nov 1997;6(4):187-95. .
Normal female anatomy

Recto-vaginal fistula
Anovestibular fistula Cloaca
305
Ileocecal Tuberculosis
Dr D Bhatnagar
This is the most common site for tuberculosis involvement of gastrointestinal Tract. This is ascribed to
increased stasis and abundance of lymphoid tissue in this area.1 About 50% cases of abdominal
tuberculosis involve gastrointestinal tract and in 42% cases ileocecal region is effected.2
Route of Infection
It occurs by one of the following mechanisms3

1. Swallowing of infected sputum. This occurs in patients with sputum positive pulmonary
disease and with laryngeal involvement. This was most important route of era when effective
treatment was not widely available. Now it is less frequent.
2. Hematogenous spread from active pulmonary, military tuberculosis or silent bacteremia
during the primary phase of tuberculosis. Most cases of abdominal tuberculosis occur as a
result of reactivation of a latent focus in the small bowel or peritoneum. Less commonly
hematogenous spread can occur from active pulmonary focus.
3. Ingestion of contaminated milk or milk products. This was a common cause of spread of
bovine buberculosis in the past. However pasteurization or boiling of milk has reduced this
mode of transmission.
4. Contiguous spread from adjacent organs. This is an infrequent mechanism, lymph node
lesions may spread the lesion to intestinal wall.
Pathogenesis
After gaining entry to gastrointestinal tract tubercle bacilli traverse the mucosa to lodge in the sub
mucosa. There the presence of bacilli induces inflammatory changes including serosal and
subserocal edema, cellular infiltrate and lymphatic hyperplasia. Appearance of granulomata cause
small papillary mucosal elevation. Subsequent lymphangitis and endarteritis lead to mucosal
ulceration, caseating necrosis and fibrosis causing narrowing of the intestinal lumen. Infection can
spread to mesenteric lymph nodes. Macroscopic lesions of the intestine can follow one of the
following patterns.
1. Ulcerative- Characterized by multiple superficial ulcers. Ulcers are circumferential and

surrounded by inflamed mucosa. This is the most common pattern occurring in about 60%
patients.
2. Hypertrophic- This is characterized by scarring, fibrosis and pseudotumour formation. Seen
in around 10% patients.
3. Ulcerohypertrophic – Characterized by an inflammatory mass with thickened and ulcerated
mucosa. It causes cone shaped deformity of the cecum, shortening of the ascending colon
and thickening of ileocecal valve, creating a wide gap. This lesion is seen in overall about
30% patients.
Clinical manifestations
Disease may occur at any age and is equally prevalent in males & females. General symptoms- Low-
grade fever, night sweats, weakness anorexia, weight loss, general lassitude.
Ulcerative Type
Patients present with abdominal discomfort, chronic diarrhoea, manifestations of
malabsorption, perforation and rarely hemorrhage.
Hypertrophic
There is usually dull aching constant abdominal pain. The pain may be described as a ball of
wind moving around the umbilicus. Associated with abdominal distension inability to pass
wind and borborygmi. Diarrhoea may follow an attack of pain. There may be episodes of
severe abdominal pain distension and frequent vomiting, this indicates sub acute intestinal
306
obstruction. Stasis in the dilated ileum above the obstruction leads to infection causing
steatorrhoea, anemia and loss of weight. Occasionally patient may present with Rt. Lower
quadrant mass. The differential diagnosis is of carcinoma cecum; appendix mass; ovarian
mass.
Investigations
1. Plain X-ray Abd – Calcified lymphnodes in mesentery may be scan,

Air fluid levels in dilated bowel lopps are seen in the presence of obstruction.
2. X ray chest- Pulmonary lesion may be present
3. U/S Abd. - An empty Rt. iliac fossa due to contractive and up ward displacement of
cecum may be present. Bowel wall thickening reveals itself as the third kidney
sign and cecal ulceration may be seen (4)
Although small lymph nodes localized to the ileocecal region are rarely seen
with ultrasound the larger distal enlarged nodes are readily visible.
4. C T Scan- Limitation of C T and U/S examination is their failure to accurately define

stenosis in the bowel in patients with threatened obstruction. Most common C
T findings are mural thickening affecting the ileocecal region either limited to
terminal ileum cr cecum or more commonly simultaneously involving both
region. This mural thickening is usually concentric but is occasionally eccentric
and it predominantly effects the medial wall. Ileocecal involvement is usually
associated with enlarged hypo dense nodes in the adjacent mesentery. Skip
areas of concentric mural thickening may be seen elsewhere in the small bowel
usually affecting the ileal loops. These segments may also show luminal
narrowing with or without proximal dilatation. The presence of such lesions in
combination with ileocecal involvement should strongly suggest the diagnosis of
tuberculosis.
5. Barium Studies- Ba meal follow through and barium enema may show mucosal ulcerations,
strictures, deformed cone shaped and retracted cecum. Incompetent
ileocecal valve, wide gap between a thickened ileocecal valve and a
narrowed ileum (Fleischner`s sign) and a fibro tic ileum that empties in to a
rigid, contracted cecum (Stierlin`s sign) (5)
6. Colonoscopy- It has the advantage of direct visualization of the lesion and biopsy from the
lesion. Colonoscopy may reveal mucosal nodules, ulcers, stricture with
nodules and ulcerations, Ileocecal valve may be edematous, deformed,
patulous.
TREATMENT
 Chemotherapy;
 Surgery Resection
 Bypass
References
rd
1. S Satya Sri- Text Book of Pulmonary and Extra pulmonary Tuberculosis. 3 Edition, 1998: 250
2. M. Monir Madkour- Tuberculosis- 2004 : 659
3. Kapoor V K – Abdominal Tuberculosis- Postgrad Med. T -1998: 74; 459
4. Kedar R P, Shah P P, Shivde R S, Malde H M- Sonographic findings in gastrointestinal and peritoneal tuberculosis. –
Clin.Radiol. 1994-49:24-29
5. Suri S; Gupta S, Suri R – Computed tomography in abdominal tuberculosis. Br. J. Radiol. 1999: 72; 92-98
307
Surgical complications of amoebiasis
Dr. Rajeev Kapoor
To understand the surgical complications of amebiasis and its management, the nature of amebiasis
must be understood.
AMEBIASIS
Amebiasis is a parasitic infection caused by the protozoon Entamoeba histolytica. It is the third
leading parasitic cause of death worldwide, surpassed only by malaria and schistosomiasis. On a
global basis, amebiasis affects approximately 50 million persons each year, resulting in nearly
100,000 deaths.
The ameba‘s life cycle has three stages: trophozoite, precyst, and cyst. Infection results from the
ingestion of cysts, usually from contaminated food or water. Excystation occurs in the lower ileum.
The resulting trophozoites are the active and growing stage of the parasite. Multiplication is by binary
fission. The trophozoites can invade the mucosa of the bowel. Invasion is probably the result of
physical means combined with production of the lytic substances from which the parasite derives its
descriptive name. If the trophozoites do not invade the bowel, they become precysts and then cysts,
finally being eliminated in the stool
According to the World Health Organization (WHO), the protozoan Entamoeba histolytica is present in
the gastrointestinal tract of more than 10% of the world‘s population. However, only approximately
10% of those harboring the parasite develop symptomatic infection. Although amebic infestation
occurs throughout the world, clinical infection is far more frequent in tropical and subtropical climates,
particularly in areas with inadequate sanitation, poor nutrition, poverty, and overcrowding. Stress,
decreased resistance, and the administration of corticosteroids can be important contributing factors.
Morphologic differences distinguish all species in the genus Entamoeba except for E. histolytica and
E. hartmanni, which are identified primarily by size. E. hartmanni was formerly known as the ―small
race‖ of E. histolytica, and is now considered saprophytic. It is the ―large race‖ of E. histolytica that
produces disease in man. Several strains or species of ameba, morphologically indistinguishable but
possibly differing in their pathogenic potential, make up the species complex known as E. histolytica.
This may account for differences in clinical findings and therapeutic results in geographically
separated centers.
Complications of amebiasis:
 Intestinal disease
o Asymptomatic infection
o Symptomatic infection
o Acute proctocolitis
o Fulminant colitis with perforation
o Toxic megacolon
o Chronic colitis
o Ameboma
o Perianal disease
 Extraintestinal disease
o Liver abscess
o Peritonitis
o Pleuropulmonary disease
o Pericarditis
Pathophysiology: The ingestion of cysts of E histolytica is followed by excystation in the small bowel
and invasion of the colon by the trophozoites. The incubation period varies from 2 days to 4 months.
Invasive disease begins with the adherence of E histolytica to colonic mucins, epithelial cells, and
leukocytes.
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After adherence, trophozoites invade the colonic epithelium to produce the ulcerative lesions typical of
intestinal amebiasis. An extracellular cysteine kinase causes proteolytic destruction of the tissue,
producing flask-shaped ulcers. Esters and protein kinase C activators augment the cytolytic activity of
the parasite.
Spread of amebiasis to the liver occurs via the portal blood. The pathogenic strains evade the
complement-mediated lysis in the bloodstream. Trophozoites ascend the portal veins to produce liver
abscesses filled with acellular proteinaceous debris. This material has the appearance of anchovy
paste. The trophozoites of E histolytica lyse the hepatocytes and the neutrophils. This explains the
paucity of inflammatory cells within the liver abscesses. The neutrophil toxins may contribute to
hepatocyte necrosis. Triangular areas of hepatic necrosis also may occur due to ischemia caused by
portal venous obstruction. The trophozoites of E histolytica may be present along the periphery of
these hepatic lesions.
Serum antibodies in patients with amebic liver abscess develop in 7 days and persist for up to 10
years. Mucosal immunoglobulin A (IgA) response to E histolytica occurs during invasive amebiasis.
However, no evidence exists that invasive amebiasis is increased in incidence or severity in patients
with IgA deficiency.
Amebic infections lead to significant morbidity while causing variable mortality as described below.
 Mortality rate in patients with uncomplicated amebic liver abscess is less than 1%.
 Fulminant amebic colitis has a mortality rate of more than 50%.
 Pleuropulmonary amebiasis has a mortality rate of 15-20%.
 Amebic pericarditis has a case fatality rate of 40%.
 Cerebral amebiasis is highly fatal, with a 90% death rate.
 Increased severity of amebiasis is noted in children (especially neonates), women who are
pregnant or postpartum, individuals who use corticosteroids, individuals with malignancy, and
malnourished individuals.
CHRONIC AMEBIC COLITIS:
This is clinically similar to inflammatory bowel disease. Recurrent episodes of bloody diarrhea and
vague abdominal discomfort develop in 90% of patients with chronic amebic colitis who have
antibodies to E histolytica. Consider amebiasis in all patients in whom inflammatory bowel disease is
suspected before administering steroids. A biopsy of colonic ulcers reveals trophozoites in patients
with amebiasis. Amebic chemotherapy suffices to cure the disease.
AMEBOMA:
This is a localized chronic infection of the cecum or ascending colon. It presents as a right lower
quadrant abdominal mass, which may be mistaken for carcinoma, tuberculosis, crohn disease,
actinomycosis, or lymphoma. Biopsy findings assist in establishing the correct diagnosis. Amebic
chemotherapy cures the disease, but there can be a stricture of the involved intestine, which will
require a limited hemicolectomy.
PROCTOCOLITIS:
An uncommon but life-threatening manifestation of intestinal amebiasis is a fulminant colitis. Early

surgical intervention and intensive antiamebic chemotherapy are essential for efficacious
management.
Most patients have an asymptomatic or benign course of the disease; however, a more aggressive
course may be found in some patients in the form of fulminant amebic colitis (FAC). Because of its
rarity, even in developing countries, the diagnosis of FAC is often delayed, and the morbidity and
mortality remain high. A more aggressive course of amebiasis might be explained by a more virulent
strain of Entamoeba histolytica or a higher susceptibility of the host.
The presence of diabetes mellitus, chronic alcoholism, and malignancy are coexistent disorders that
might increase the susceptibility of the patients. There is a difficulty in diagnosing fulminant amebic
colitis, even in a high prevalence zone of amebiasis. Clinical data that may support suspicion of the
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disease are abdominal pain, diarrhea with rectal bleeding, rectal tenesmus, and fever or a toxic
clinical picture. Although more rare, massive lower gastrointestinal bleeding may be caused by FAC,
and these patients may also have toxic manifestations.
Early and aggressive surgical treatment is recommended. It should be noted that FAC is a severe
disease with high rates of mortality, even with surgical treatment. Initial management may be medical,
but patients should be carefully evaluated and undergo surgery promptly if there is an acute
abdominal syndrome, suspicion of complications, or no response to medical treatment.
The criteria for chronic ulcerative colitis according to Truelove and Witts may also be applicable for
patients with FAC and may help to decide the severity of fulminant colitis. However, once surgical
treatment is decided, standard colonic resections, as required by the portion of the colon involved,
should be performed.
It is considered safer not to perform a primary anastomosis in most cases of FAC because of a high
risk of anastomotic disruption. Delay in diagnosis or the lack of diagnosis, absence of surgical
treatment, or use of surgical procedures other than colonic resections contributed to increased
mortality.
PERIANAL DISEASE:
Intestinal amebiasis may produce skin infections in the area around the patient's anus (perianal).
These ulcerated areas have a "punched-out" appearance and are painful to the touch. Biopsy and
amebic chemotherapy is required. Abscesses have to be drained and fistulae have to be treated like
any fistula in ano is treated.
AMEBIC LIVER ABSCESS
When amebae invade the colonic mucosa, particularly in the cecum, they may be carried to the liver
through the portal venous system, where they lodge in the venules, producing thrombosis that is
followed by an infarct, necrosis of liver tissue, and a localized abscess. This is not an abscess in the
classic sense, but rather a collection of necrotic liver tissue with white blood cells and amebae. The
amebae in the periphery multiply, releasing lytic enzymes, resulting in additional necrosis and
enlarging the abscess. No fibrous capsule or clear margin exists between the abscess and the
surrounding tissue. Although the parasite does not normally stimulate the intense inflammatory
response like other infective agents, it may do so under certain conditions, particularly if secondarily
infected.
Right lobe liver abscess is more common than the left lobe abscess, the incidence being 55-85%.
Multiple abscesses are present to the tune of 27%. Although these abscesses may occur at any age;
they are most frequent in the third to fifth decades of life. In adults, men are infected seven to nine
times as often as women; in children, no sex difference is noted.
Symptoms of an amebic liver abscess may be present for a few days to many weeks before the
patient seeks help. In the experience of one of us (FCE) and associates (1978), the average duration
was 33 days. Symptoms vary, and as a result, the diagnosis is not clear in one third of cases. Pain in
the right upper quadrant with or without fever is the most common presentation. Anorexia and malaise
are usual, and patients whose treatment has been delayed may have profound weight loss. Blood in
the stool is noted in only about 25% of patients. Many patients present with tender hepatomegaly.
Softening suggests imminent rupture of the amebic liver abscess. In addition, intercostal pressure
reveals tenderness. Pleural effusion is common. Jaundice is uncommon, but when present, it is
associated with a poor prognosis.
Leukocytosis (12,000 to 30,000 cells/mm) is the rule. Liver function tests show moderate elevation of
alkaline phosphatase, bilirubin, and transaminases. Serologic tests, if positive, suggest current or
previous invasive amebiasis. The enzyme-linked immunosorbent assay (ELISA) technique is highly
sensitive, is easily available, and can be completed in about 35 minutes. The test may be negative in
the first week; the titer may peak in 3 months and decrease to lower but detectable levels in 9 months.
This test may not be very useful in endemic areas, where widespread colonic invasion of ameba
results in high titers without hepatic involvement. In these areas, its value remains in differentiating it
310
from pyogenic liver abscess and other cystic lesions of the liver. Liu and colleagues (2001) described
the usefulness of the polymerase chain reaction (PCR) in confirmation of the diagnosis of amebiasis
by amplification of 16S ribosomal RNA. Chest radiography usually shows an elevated diaphragm,
often accompanied by a pleural effusion. Computed tomography (CT), ultrasonography, magnetic
resonance imaging (MRI), and isotopic imaging all demonstrate both the presence and site of liver
abscesses. However, in the acute situation, CT, MRI, and isotope imaging are not any better than
ultrasonography. Ultrasound is inexpensive, is easy to perform, and has a diagnostic accuracy of
90%. Ultrasound is the best investigation for following the size of the abscess on treatment.
When aspirated, the pus is usually reddish brown or chocolate brown, the so-called anchovy sauce,
although initially, it may be yellowish or even white. Unless the amebic liver abscess was aspirated
previously, it is bacteriologically sterile. Amebae can be demonstrated in approximately one half of the
abscesses.
Because of the lytic nature of the parasite and the lack of encapsulation of amebic liver abscesses,
rupture occurs in 10% to 30% of patients. The usual anatomic location of amebic liver abscesses
makes upward or transdiaphragmatic rupture more frequent than infradiaphragmatic rupture
Treatment: Based on a study of 213 consecutive patients treated by the authors, amebic liver abscess
is best treated non-operatively if the volume of the abscess is assessed to be less than 220 ml at the
time of initial presentation where the chance of complete resolution is extremely high, as opposed to
abscesses which are larger. (Unpublished data)
The indications for early aspiration/drainage of the amebic liver abscess are large abscesses at
presentation (>220 ml volume), left lobe abscess, multiple abscesses, failure of medical therapy,
pleuropulmonary amoebiasis and acutely sick patients. However, when possible, antiamebic
chemotherapy should precede any form of intervention for at least 72 hours. CT or ultrasound
percutaneous aspiration/drainage is simple and safe to perform. Laparotomy is indicated only in
patients with multiple liver abscesses which are inaccessible for percutaneous drainage or in patients
in whom percutaneous drainage and medical management have failed to improve the condition of the
patient or patients with peritonitis because of ruptured amebic liver abscess.
THORACIC AMEBIASIS
In amebiasis, 70% to 97% of thoracic complications result from extension of an amebic liver abscess
through the diaphragm. The type of complication depends on whether the pleural space, lung, or
pericardium is involved, either singly or in combination. We shall consider only pleural and pulmonary
involvement.
Most patients have clinical features of an amebic liver abscess in addition to those related to the
thoracic complication.
Pleural Involvement
An amebic liver abscess adjacent to the diaphragm may produce diaphragmatic irritation and a
sympathetic pleural effusion. On chest radiography, the diaphragm is elevated and fixed. The
costophrenic angle is obliterated. The incidence of sympathetic pleural effusion can be as high as
34% in patients with amebic liver abscess. Thoracentesis shows that the fluid is clear or
serosanguineous and sterile on culture. Amebae are not present. This pleural effusion requires no
specific therapy other than that for the causative liver abscess. Should it increase, however, it may
presage the rupture of the abscess through the diaphragm and the development of frank empyema.
Basal pneumonitis and atelectasis, alone or in combination, are the other complications of an
unruptured liver abscess. Ten percent of the patients had basal pneumonitis or atelectasis; 22% of
our patients with unruptured amebic liver abscess had pleural effusion, pneumonitis, or both.
Amebic Empyema
Excluding sympathetic pleural effusion, amebic empyema is the most common of all the
pleuropulmonary complications, occurring in 50% to 75% of patients with thoracic amebiasis. In 95%
of patients, the empyema is on the right side. Elevation of the diaphragm, friction rub, and effusion
311
usually precede it. The onset can be either insidious or rapid and overwhelming, depending on the
size of the perforation and the volume of the abscess. It is accompanied by pain, dyspnea, and shock
if the volume is massive. Some patients complain of a tearing sensation. Radiography of the chest
shows opacification of the ipsilateral lung field.
On thoracentesis, purulent, reddish brown or bile-stained fluid is found. During both chest aspiration
and establishment of intercostal tube drainage, it is mandatory to approach through a high right lateral
intercostal space near the axilla to avoid entry through the already raised diaphragm into the liver.
Unless the lung is also involved, the fluid is sterile. Amebae are identified in less than 10% of cases.
Pleural thickening, often out of proportion to the duration of the empyema, follows rapidly, especially
in the presence of secondary infection. Accordingly, treatment must be prompt and vigorous to avoid
further complications. In addition to specific drug therapy, the purulent exudate must be removed
rapidly. Although repeated aspirations, often combined with the instillation of streptokinase, have been
recommended, we agree with Ibarra-Pérez (1981) that closed intercostal drainage with the largest
cannula possible, combined with strong suction, offers the best chance for prompt and complete
reexpansion of the lung. When carried out promptly, secondary surgical procedures other than an
occasional rib resection are rarely required. Le Roux and associates (1986) pointed out that subcostal
drainage of the amebic liver abscess might be necessary when drainage persists or abscess
becomes secondarily infected. Should initial treatment be delayed or inadequate, reexpansion of the
lung may be limited and decortication needed.
The mortality rate varies from 14% to 40%, depending on the general condition of the patient and the
delay in starting treatment.
Pulmonary Amebiasis
Two types of pulmonary amebiasis occur. The first results from rupture of an amebic liver abscess
into the lung, and the second are metastatic (i.e., hematogenous dissemination with no direct
communication to the liver). The former is by far the more common.
When pleural symphysis precedes the transdiaphragmatic rupture of amebic liver abscess, the lung is
directly involved, particularly the basal segments, the middle lobe, or rarely the lingula. Following a
few days of chest pain and nonproductive cough, the patient complains of expectoration of reddish
brown or bile-stained material, sometimes in large quantities. Unless flooding of the tracheobronchial
tree is overwhelming, the prognosis is good.
Treatment consists of postural drainage, antibiotics to prevent secondary infection, and, most
important, specific antiamebic drug therapy. This complication carries the lowest mortality rate of any
of the major complications of amebiasis because the liver abscess is usually well walled off from the
peritoneal and pleural spaces. In rare cases in which the adhesions are not well formed, rupture of the
liver abscess can be into the pleura as well as the bronchi simultaneously. Pleural drainage is
required along with the other measures.
Rarely, a persistent bronchobiliary fistula develops. Ragheb and associates (1976) performed lung
resection and closure of the fistulous tract.
Occasionally, lung involvement is followed by bronchiectasis, usually mild and not severe enough to
require resection.
Metastatic pulmonary amebic lung abscesses are rare and result from hematogenous spread of
amebae. Symptoms resemble those of other lung abscesses, with fever, chest pain, cough, and
hemoptysis. Occasionally, these parenchymal abscesses rupture into the pleura and produce a
localized empyema. Unless amebae can be demonstrated in the sputum or the pleural fluid, the
diagnosis of pulmonary amebiasis is difficult and depends on finding evidence of amebiasis
elsewhere.
Treatment is similar to that for any other lung abscess, with the addition of specific antiamebic drug
therapy.
312
In approximately 25% of patients, both the pleura and lungs are involved. Treatment includes
intercostal drainage with strong suction, reexpansion of the lung, postural drainage, and appropriate
antibiotics.
PERICARDIAL AMEBIASIS
Amebic pericarditis is a rare complication of liver abscess. Lamont and Pooler reported the frequency
as 2.8 percent in a study of 250 cases of hepatic amebiasis. Pericardial amebiasis has always been
considered as a serious and often fatal complication of amebiasis. However, survival has become
quite possible after early recognition of the illness and prompt treatment. This complication is mostly
due to rupture of a left lobe liver abscess.
The diagnosis of amebic pericarditis is established on the following findings:

1. Anchovy sauce from the pericardium,
2. Demonstration of Entameba histolytica in the culture,
3. The dramatic response that follows specific antiamebic therapy.
There are three phases of involvement of pericardium in amebiasis:

1. Initial sympathetic or slightly purulent effusion.
2. This is followed by intrapericardial rupture of hepatic abscess often associated with shock and
cardiac tamponade.
3. Development of constrictive pericarditis. Constrictive pericarditis is likely to be met as a
complication following recovery from the acute illness.
These have to be treated like any pericardial effusion; amebic chemotherapy is a must. Cultures and
broad spectrum antibiotics may be required.
ANTIAMEBIC CHEMOTHERAPY
The mainstay of treatment for all forms of amebiasis including its complications is antiamebic
chemotherapy. Additional specific treatment protocols are required for various complications including
pleuropulmonary amoebiasis.
Nitro-imidazole derivative Group:

Most amebic liver abscesses are treated with metronidazole, 750 mg orally or 500 mg
intravenously three times per day. Metronidazole produces little toxicity. Oral administration in
high doses may be associated with nausea, anorexia, a metallic taste in the mouth, cramps,
and diarrhea. These problems are less common with the intravenous route. The duration of
the therapy is 14 days.
Tinidazole is as effective as metronidazole and may be better tolerated. However, a repeat

therapy is sometimes required when used and thus we do not recommend its routine use.
The recommended dosage in amebic liver abscess is 800 mg three times daily for 5 days or 2
g daily for 3 days. In children, 50 to 60 mg/kg is given up to a maximum of 2 g. Other
nitroimidazole derivatives like nimorazole, secondizole, and ornidazole have produced poorer
results than metronidazole and tinidazole.
More recently, satranidazole, 300mg twice a day orally for 10 days have proved to be as
effective as metronidazole with a significantly better tolerance.
Chloroquine
Chloroquine is generally well tolerated and particularly effective in the amebic liver abscess
as the drug is concentrated in the liver. It is also effective in pulmonary amebiasis. At the
dosage levels used in the treatment of amebiasis, the retinopathy sometimes associated with
long-term use of chloroquine does not occur. It should, however, be administered orally,
which is not always possible in seriously ill patients.
Dehydroemetine
Dehydroemetine is no longer in routine use because of its cardiotoxicity and as the other
drugs are equally efficacious. If required the dosage schedule is mentioned in table. The drug
313
is contraindicated in renal and cardiac disease and must be cautiously used in children and
elderly patients.
Because relapse has been reported after the use of metronidazole alone and because patients with
complicated amebiasis are sicker than patients with uncomplicated amebic liver abscess, we prefer to
use a combination of drugs
When diagnosis is delayed, results may be devastating. The increasing use of sonography has
permitted earlier diagnosis and treatment of amebic liver abscess.
Patients with complications because of amebiasis, usually have been sick for a long time and are
often economically disadvantaged and malnourished. Consequently, nutritional support is important.
Recommended Antiamebic Drug Schedule
Drug Route of Administration Dose Duration (d)

750 mg t.i.d. (children: 35–50
Metronidazole Oral a 14
mg/kg in 3 divided doses for 10
or d)
Tinidazoleb Oral 3
800 mg t.i.d. or 2 g o.d
or
Satranidazole Oral 10
300mg b.d
c
Chloroquine Oral 600 mg (base) b.i.d. 2
followed by 300 mg (base) 19
b.i.d.
Dehydroemetined Intramuscular 1–1.5 mg/kg (maximum of 90 5–10
mg)
a
Patients unable to tolerate metronidazole orally should receive it intravenously.
b
For children, the dose is 50–60 mg/kg, up to a maximum of 2 g. The drug may have to be
repeated in case of sub optimal response
c
For children, 16 mg/kg (salt) daily for 21 days.
d
The drug should be administered for the least number of days necessary to control severe
symptoms (usually 3–5 days). For children, the daily dose is divided. Marked toxicity is
unlikely if used less than 7 days.
References
1. Eggleston FC, et al: The results of surgery in amebic liver abscess: experiences in 83 patients. Surgery 83:536,
1978.
2. Eggleston FC: Pitfalls in the surgical management of ALA. Trop Doc 9:178, 1979.
3. Faust EC, Russell PE: Clinical Parasitology. 7th Ed. Philadelphia: Lea & Febiger, 1964.
4. Ibarra-Pérez C. Thoracic complications of amebic abscess of the liver: report of 501 cases. Chest 79:672, 1981.
5. Jain NK, et al: Hepatopulmonary amebiasis. Efficacy of various treatment regimens containing dehydroemetine
and/or metronidazole. J Assoc Physicians India 38:269, 1990.
6. Khanna S, Chaudhary D, Kumar A, Vij JC Experience with aspiration in cases of amebic liver abscesses in an
endemic area. Eur J Clin Microbiol Infect Dis 24: 428-430, 2005.
7. Knappik M, Borner U, Jelinek T Sensitivity and specificity of a new commercial enzyme-linked immunoassay kit
for detecting entamoeba histolytica IgG antibodies in serum samples. Eur J Clin Microbiol Infect Dis 24: 701-703,
2005.
8. Le Roux BT, et al: Suppurative diseases of the lung and pleural space. I. Empyema thoracis and lung abscess.
Curr Probl Surg 23:1, 1986.
9. Liu CJ, et al: Amebic liver abscess and human immunodeficiency virus infection: a report of three cases. J Clin
Gastroenterol 33:64, 2001.
10. Muzzafar J, Madan K, Sharma MP Kar P Randomized, single-blind, placebo-controlled multicenter trial to compare
the efficacy and safety of metronidazole and satranidazole in patients with amebic liver abscess. Dig Dis Sci 51:
2270-2273, 2006.
11. Ragheb MI, Ramadan AA, Khalil MAH: Intrathoracic presentation of amebic liver abscess. Ann Thorac Surg
22:483, 1976.
314
12. Sharma M, et al: A simple and rapid Dot-ELISA dipstick technique for detection of antibodies to Entamoeba
histolytica in amebic liver abscess. Ind J Med Res 88:409, 1988.
13. Verghese M, et al: Management of thoracic amebiasis. J Thorac Cardiovasc Surg 78:757, 1979.
315
Perianal fistulae
Dr. B.K.Jain, D.Mohanty
Anal fistula of cryptogenic origin is the most frequent condition presenting as perianal fistula. A clear
understanding of the underlying pathology and the anatomy of the fistula is required for appropriate
management of anal fistula. Recurrence and anal incontinence are the most important concerns
following surgical management of anal fistula.
Differential diagnoses of perianal fistulae
Anal fistula of cryptogenic origin: It is the most common condition presenting as perianal fistula. It
is caused by infection of the anal gland.
Crohn‘s disease: It should be suspected if there are numerous complex fistulous tracts associated
with edematous skin tags or if there is inflammation of rectal mucosa1.
Tuberculous anal fistula: It is diagnosed in a small proportion (about 15% - 18% in India) of patients
based on histopathology of the excised tract.
Hidradenitis suppurativa: In this condition, the disease arises from perianal skin and not from the
anal crypts.
Actinomycosis: Sulphur like granules are seen in the abscess cavity or fistulous tract.
Pilonidal sinus: It may mimic posteriorly located anal fistula, however the examination should reveal
presence of hair in the tract and absence of communication with anus.
Urethral fistula: It may develop following rupture of a periurethral abscess and is situated anterior to
anus.
Pathology of anal fistula
Majority of anal fistulae develop as a consequence of infection in anal glands which communicate with
anal crypts (cryptoglandular disease). The infection leads to the formation of an abscess in the
intersphincteric space of the anal wall. The abscess may spread in one or more directions giving rise
to anorectal abscess in several locations, and subsequently anal fistulae.
The extrasphincteric fistulae are caused by pelvic diseases – appendicular abscess, diverticulitis,
Crohn‘s disease, foreign body impalement in rectum, penetrating injury. Some cases may be
iatrogenic.
Classification of Anal fistula
According to Parks classification, the anal fistulae are classified into four main subgroups depending
on the course taken by the primary tract: intersphincteric, transsphincteric, suprasphincteric, and
extrasphincteric2 (Figure 1). Intersphincteric fistula seems to be the most frequent type.
316
Extrasphincteric
Suprasphincteric Fistula
fistula
Transhincteric
fistula
Intersphincteric
fistula
Figure 1: Types anal fistula
A fistula which is simple to treat by one stage surgical procedure without significant risk of
incontinence or recurrence is classified as a simple fistula. Complex fistulae may require staged
procedures, management being associated with higher risk of incontinence or recurrence.
Presenting symptoms
Most of the patients have previous history of anorectal suppuration. The patient usually complaints of
purulent or serosanguinous discharge from an opening in perianal area. Episodes of ‗increasing pain,
fever, and pain during defecation‘ followed by mucopurulent discharge and relief of pain are reported.
Clinical assessment
Thorough clinical examination provides valuable information regarding the anatomy of the fistulous
tract and its complexity. The number and position of the external opening (EO) – a small pit
surrounded by scar or granulation tissue - should be noted. Increasing number and increasing
distance of EO from anus suggest possibility of complex anal fistula.
Palpation around the EO may reveal a palpable tract and its direction to indicate the position of
internal opening (IO). Palpation of a tract directed from EO to the anus excludes the possibility of
diagnoses unrelated to anorectum e.g. periurethral fistula or pilonidal sinus. Palpation of tract,
throughout its extent from EO to anus is a hallmark of a simple anal fistula.
On digital rectal examination (DRE), the IO may be felt as a pit, depression or an indurated nodule,
the most frequent location being 6 o‘clock at the level of dentate line. Proximal or distal location of the
IO in anal canal indicates the complexity of the fistula. The more proximal is the IO; larger is the
proportion of sphincter likely to be encircled by the tract, making the management more difficult.
Injection of saline, methylene blue, or diluted hydrogen per oxide through EO may facilitate
identification of IO in difficult situation. DRE also allows assessment of resting anal tone and anal
pressure on squeeze. Probing of fistula during clinical examination is inadvisable on account of undue
discomfort to the patient and high risk of creating a false tract.
Careful palpation of anal canal and distal rectum may reveal submucous abscess or tract, or
sometimes an intersphincteric tract or a supralevator abscess. Presence of palpable abnormalities in
upper anal canal or lower rectum indicate complex fistula. Anoscopy may reveal mucosal
inflammation as a clue to associated Inflammatory bowel disease.
Special studies
In only a few cases, the use of sophisticated imaging techniques is required. Sigmoidoscopy should
be undertaken for detecting neoplasms, inflammatory bowel disease, or secondary tracts in rectum.
Fistulography has been reported to be unreliable compared with operative findings3. Transanal
317
ultrasound can delineate the anatomy of the anal sphincters in relation to an abscess or a fistula. It is
more efficient in intersphincteric tracts. Magnetic Resonance Imaging (MRI) is useful in identifying
primary and secondary tracts. High concordance rates between MRI and operative findings have
been reported4. CT may be useful in assessment of associated pelvic pathology in patients with some
complex anal fistulae. Anal manometry is useful for identifying patients at greater risk for incontinence
following fistula surgery.
Treatment
Symptoms should always guide the need for the intervention5. There are three main surgical
techniques for treatment of anal fistulae: fistulotomy, use of seton, and advancement flaps. Complex
anal fistulae like transsphincteric fistulae with high tract and supralevator fistula require staged
procedures. The procedures involve use of a seton (Figure 2), or the technique of flap advancement
in addition to partial fistulotomy. Rarely colostomy may be required to control sepsis when usual
methods of treatment fail.
Partial fistulotomy
& drainage of
supralevator
collection
Suprasphincteric
fistula with supra
levator collection
Obliteration of
supralevator extention
Seton placement
Figure 2: Surgical procedure for complex anal fistula
The procedures practiced for treatment of anal fistulae may require division of some part of internal
and or external sphincter. Temporary or permanent incontinence for flatus, liquid, or formed stool may
develop following surgery depending on the amount of sphincter divided and the method used to
divide the sphincter.
Fistulotomy
Fistulotomy is an adequate procedure for simple anal fistulae. Most of the intersphincteric fistula and
transsphincteric fistula with a low lying tract can be treated by this technique. During fistulotomy, a
probe is passed through the fistulous tact, and the tract is laid open by dividing the tissues overlying
the tract – skin, subcutaneous tissue, lower fibers of internal and external anal sphincters. A search
should be made for any secondary tract arising from the primary tract which may need curettage. The
laid open tract may be marsupialized by suturing it to the skin edges to hasten the healing.
Fistulectomy, currently a less used procedure, involves excision of the whole fistulous tract. It results
in larger wound in comparison to fistulotomy. It may be useful in situations where it is not possible to
pass the probe due to partial obliteration of the tract or it is necessary to provide tissue for histologic
evaluation.
Seton Placement
Seton is a foreign material which is inserted in to the fistula tract to encircle the sphincter muscle. It
may be made of silk, nylon, polypropylene, silicone, or steel. The seton is used in management of
318
fistula in several ways: marking seton, draining seton, staging, or cutting seton. As marking seton, it
may help the surgeon to assess, once the patient is awake, the amount of muscle the fistula tract
crosses. If adequate muscle is present above the seton, fistulotomy may be performed with out
significant risk of incontinence.
A loosely tied seton may provide drainage for septic process. The seton drainage converts anal gland
sepsis into a foreign body reaction, which in most of the cases (75%) will subside spontaneously once
the seton is removed after a period of 8-12 weeks5. In combination with immunomodulation therapy
with infliximab, long term drainage seton appears to improve outcome while maintaining sphincter
function in Crohn‘s disease with complex anal fistula6.
Cutting seton is used to gradually divide the sphincter muscle. At regular interval, the seton is
tightened, dividing the muscle by a process of ischemic necrosis. The cut edge of the muscle does not
retract because of the fibrosis induced by the seton. Use of a looped seton for this purpose facilitates
the process7. While using a staging seton, the superficial fistulous tract is divided up to the sphincters,
the seton is placed in the remaining portion of the tract passing through the sphincter, and tied around
the sphincter. The encircled portion of the sphincter is divided as a second stage procedure, once
adequate fibrosis occurs.
Medicated Ayurvedic thread has been also used, as temporary draining seton, in treatment of anal
fistula8.
Advancement flaps
Mucosal advancement flap or island flap anoplasty have been used to close the internal opening after
the fistulous tract has been debrided. This technique should be accompanied by adequate external
drainage and wide saucerization. It obviates the need for dividing the sphincter.
Other treatment
A mixture of fibrinogen and thrombin is injected in the fistula tract after it has been curetted. Success
rate varying from 14% to 69% has been reported. Similarly biodegradable ‗collagen plug‘ has been
used with promising results9.
To summarize, anorectal fistula of cryptoglandular origin is the most common condition presenting as
perianal fistulae. A good clinical examination provides all information required for the management of
anorectal fistulae. Fistulectomy and seton placement are the most frequently used techniques for
surgical management of anorectal fistulae.
References
1. Lowney JK, Fleshman Jr. JW, Benign disorders of the anorectum (Pelvic floor, fissures, hemorrhoids, and
th
fistulas). In; Zinner MJ, Ashley SW (eds). Maingot‘s Abdominal Operations, 11 ed. New York, McGraw Hill
Medical, 2007:663-691
2. Park AG, Gordon PH, Hardcastle JD. A classification of fistula-in-ano. Br J Surg 1976; 63: 1
3. Kuijpers HC, Schulpen T. Fistulography for fistula in ano: Is it useful? Dis Colon Rectum 1985; 35:103
4. Barker PG, Lunnis PJ, Armstrong P. et al. Magnetic rasonance imaging of fistula-in-ano: Technique,
interpretation, and accuracy. Clin Radiol 1994; 49:7
nd
5. Belliveau P. Anal fistula. Fazio VW, Church JM, Delaney CP (eds). Current therapy in colon and rectal surgery, 2
edition. Philadelphia, Elsevier Mosby, 2005: 27-34.
6. Topstad DR, Panaccione R, Heine JA et al. Combined seton placement, infliximab infusion, and maintenance
immunosuppressives improve healing rate in fistulizing anorectal Crohn‘s disease. Dis. Colon Rectum. 2003; 46:
577.
7. Jain BK, Gupta A. Simple method of tightening cutting setons. Br J Surg 1995;82: 996-1004
8. Shukla NK. Collaborating centres ICMR. Multicentric controlled trial of Kshaarasootra (Ayurvedic medicated
thread) in the management of fistula in ano. Indian J Med Res 1991; 94:177-85.
9. Johnson E, Gaw JU, Armstrong DN. Efficacy of biodegradable ‗collagen plug‘ versus fibrin glue in closure of
anorectal fistula. Dis. Colon Rectum. 2005; 48: 631.
319
Pre-operative bowel preparation
Dr. Vivek Agrawal, Dr. Mohit Joshi
INTRODUCTION
During early part of twentieth century mortality from colorectal surgery was very high, developing
secondary to sepsis. Owing to sustained improvement in surgical techniques, perioperative & ICU
care, and an armamentarium of variety of generations of numerous antibiotics, the postoperative
morbidity and mortality have come down. Yet, infectious complications, especially wound infections
and intestinal anastomotic line dehiscences remain a significant cause of concern in patients
undergoing colorectal surgery. Pre operative bowel preparation had played a significant role in
reforming intestinal surgery, especially colorectal surgery. Numerous combinations and regimens
exist for bowel preparation and the one that is often used is based on Surgeon‘s preference and
experience rather than well documented and accepted evidences.
The ideal bowel preparation aims to rid the colon and rectum of solid stool and fecal contents in
minimum possible time so as to lower the bacterial load, to make the bowel aesthetic and
manageable. This aims at reducing the incidence of postoperative anastomotic disruptions and
serious infectious complications. The preparation, in addition to being inexpensive should also be
patient compliant, without causing any discomfort and must not cause shift of fluids and electrolytes in
the body‘s milieu interior. Unfortunately, no single preparation currently available meets all of these
requirements.
Though many recent prospective randomized studies have failed to demonstrate a benefit of reducing
the rate of complications following mechanical bowel preparation, it still finds a prime place in low or
very low anterior resections. Rather, the role of prophylactic antibiotics plays a significant role in
colorectal surgery in prevention of wound infection. Studies have demonstrated that the preparation of
bowel and colon can be limited to those patients who are to undergo investigative, radiological and
endoscopic procedures only, wherein chances of missing lesions is high because of feces in
unprepared bowel.
HISTORICAL PERSPECTIVE
Colorectal surgery performed prior to 1970 was fraught with postoperative infectious complications,
which used to occur in more than 30-50% of all such operations performed. Diversion of the fecal
stream appeared mandatory when operating on an emergent basis, thereby requiring the
performance of multiple, staged operations instead of a single stage surgery encompassing resection
and primary anastomoses.
With the advent of endoscope for direct visualization of bowel through colonoscopy, gut preparatory
methods evolved from those used in radiologic and surgical practices1. Early preparations used
dietary limitations, cathartics, and enemas. Although these preparations cleansed the colon, they
were time consuming (48-72 hrs), uncomfortable for the patient, and associated with fluid and
electrolyte disturbances2.
Hewitt et al in 19733 introduced a rapid preparation using high volume (7-12L) oral gut lavage with
saline or electrolyte solution. This was associated with severe fluid and electrolyte shifts and poor
patient tolerance.
Irvin and Goligher4 in 1973 proposed that poor mechanical bowel preparation (MBP) is associated
with higher rate of anastomotic dehiscence and that MBP minimizes the risk of fecal impaction at the
anastomotic site, thereby reducing undue tension and ischemia at that site, and thereby reducing the
risk of dehiscence consequently. However, lately the role of MBP has been disputed by a number of
authors5,6,7,8.
In 1980, Davis et al. formulated polyethylene glycol (PEG), an osmotically balanced electrolyte lavage
solution9. The standard 4L dosing regimen given the day before the procedure was established as
safe and effective10,11,12. PEG quickly became the ―gold standard‖ for bowel preparation. However, its
poor patient compliance related to the salty taste, the bad smell from the sulfates, and the large
320
volume of fluids required that had to be consumed in a short time led to the need of modifying the
PEG solutions. Their dosing recommendations were redefined. Evaluations of other osmotic laxatives
(e.g. sodium phosphate)13,14,15 was also done and brought into practice. Chang et al. developed a
method of pulsed rectal irrigation combined with magnesium citrate16. These regimens and their
utilization still continue to evolve. More recent studies have focused on identifying the ―ideal‖
preparation having various patient friendly characteristics including such parameters as palatability,
electrolyte supplementation, the optimum timing and the distribution of doses.
METHODS OF BOWEL PREPARATION
Bowel preparation incorporates two aspects:

A. Mechanical bowel preparation
B. Antimicrobial bowel preparation
A. MECHANICAL BOWEL PREPARATION
MBP aims to reduce the fecal load of the gut. Although the total number of colonic microorganisms is
reduced by mechanical cleansing, it must be stressed that mechanical bowel preparation alone does
not alter either the concentration or the spectra of residual bacteria17. Therefore, incidence of
postoperative wound infection is not to be expected to decline through MBP alone. Moreover,
incidence of wound infections after colorectal surgery has been found to be significantly higher when
MBP is used alone for bowel preparation as compared to when MBP is combined with administration
of antibiotics17that are effective on intraluminal organisms. Adequate MBP requires total emptying of
colon with no liquid feces remaining in the large bowel though, some amount of liquid feces may elude
evacuation which may then spill during bowel surgery while handling the bowel.
Characteristics of ideal method of bowel preparation should be-

i) simple
ii) inexpensive
iii) without distress or discomfort to the patient
iv) without side effects viz. fluid and electrolyte imbalance.
v) reduce the bacterial load.
vi) evacuate all feces.
vii) cause no change to gut anatomy and physiology.
The various techniques of MBP currently available are discussed with respect to patient‘s
acceptability, efficiency, influence on fluid and electrolyte imbalance and influence on fecal micro flora.
1. CONVENTIONAL METHOD
It involves giving a low residue or clear liquid diet and combined with purgation using
laxatives and rectal enemas. It provides satisfactory cleansing in about 70% of patients18
(Table 1). The drawbacks include poor patient compliance, exhaustion of the patient,
diminished nutritional intake, a high incidence of abdominal pain and fatigue.
2. ELEMENTAL DIETS
The use of low residue elemental diet results in a low fecal bulk, although it does not empty
the colon. It produces satisfactory cleansing in only 17% of patients18. Although elemental
diets are well tolerated, evidence is lacking to advocate these elemental diets as a sole
means of bowel preparation.
3. WHOLE GUT IRRIGATION

It necessitates placement of nasogastric tube and infusion of warmed saline or balanced
electrolyte solution through it at a constant rate of 50-75 ml/min into the stomach. Most
patients start having their first bowel movement 40-60 minutes after initiation of irrigation,
which is continued until the effluent is clear. This usually takes about 4 hours and requires 7-
12 liters of perfusate. Since whole bowel irrigation with saline is associated with water and
sodium retention, it might be hazardous in elderly and in patients with cardiopulmonary or
321
renal disease; as this may predispose to the risk of cardiac failure. Because of risk of
electrolyte imbalance, isotonic electrolyte solutions are preferred to be used for irrigation.
It provides satisfactory cleansing in 90% of patients (Table 1). Disadvantages include

placement of nasogastric tube, abdominal distension, nausea, vomiting17and colics. It is now
sparingly used.
4. MANNITOL
Mannitol acts as an osmotic agent, draws fluid into the bowel and produces purgation by
irrigating the colon. It can be used either as an isotonic (5%= 200g/4L) or hypertonic solution
(10%= 200g/2L or 20%= 200g/1L). Usually it is taken a day before surgery over a four hour
period. If an isotonic solution is used, at least 4 L must be ingested to produce adequate
cleansing of the colon. Ingestion of such large volume over short time causes abdominal
discomfort and nausea. In addition to this there are two major drawbacks of using Mannitol for
MBP. First, it increases the post operative wound infection rate as compared with other
solutions used for MBP19,20. Secondly, there is production of potentially explosive gases within
the colonic lumen such as methane and hydrogen due to its fermentation21. Following
preparation by mannitol, colonic explosions have been reported after colonoscopic
polypectomy and after diathermy incisions of the colon22,23. Because of these serious
considerations mannitol is now rarely, if ever, used in current clinical practice.
5. POLYETHYLENE GLYOL (PEG)

PEG is an isotonic lavage solution containing PEG (3350 mmol/L). It acts as an osmotic
purgative and usually comes as a balanced electrolyte solution containing polyethylene glycol
(3350 mmol/L), sodium (125 mmol/L), chloride (33mmol/L), potassium (10mmol/L) and
bicarbonate (10mmol/L).
To achieve adequate cleansing an average of 4L of PEG solution must be ingested over 4

hours. Although PEG is generally well tolerated, 5-15% of patients do not complete the
preparation because of poor palatability and/or large volume. The timing of PEG doses has
also proven to affect the quality of the bowel preparation. PEG taken in divided doses (3L in
the prior evening and 1L the morning of the procedure) was demonstrated to be as effective
and better tolerated than the standard 4L dose given one day prior to the procedure. PEG
provides satisfactory cleansing in more than 90% of the patients10,19.
6. SALINE LAXATIVES
Saline laxatives are available as-
 Magnesium citrate
 Picolax (sodium picosulfate plus magnesium citrate)
Magnesium citrate is a hyperosmotic saline laxative that increases intraluminal volume

resulting in increased intestinal motility. Magnesium also stimulates the release of
cholecystokinin which causes intraluminal accumulation of fluid and electrolytes and promotes
small bowel and, possibly, colonic transit.
Since magnesium is eliminated from the body solely by the kidneys, magnesium citrate
should be used with extreme caution in patients with renal insufficiency or renal failure.
Sodium picosulfate is a stimulant purgative that acts on the left colon after being acted upon
by colonic bacteria.
With Picolax the advantages of these two solutions are combined; where magnesium citrate
cleanses the proximal large bowel and latter the distal half. Two sachets containing 10 mg of
sodium picosulfate and 13 gm magnesium citrate are administered a day before surgery. It
provides effective cleansing in 46% of the patients (Table 1).
7. SODIUM PHOSPHATE
Aqueous sodium phosphate is a highly osmotic cathartic solution which contains 48g
(400mmol) of monobasic sodium phosphate and 18 g (130mmol) of dibasic sodium
322
phosphate per 100 ml. Two doses of 30-45mL (2-3tbsp) of oral solution are given at least 10-
12 hours apart.
Its advantages include a greater patient acceptability, superior rapid colonic cleansing, safety
and less cost as compared to PEG based solutions14. Potential disadvantages include the
concern of hypovolemia as significant fluid and electrolyte shifts can occur. It provides
satisfactory bowel cleansing in 80-85% of the patients.
TABLE 1: Efficiency of various methods of Mechanical Bowel Preparations26
Method Author(s) Satisfactory cleansing(%)

1. Conventional MBP Keighley 66
DiPalma et al 69
2. Elemental diets Keighley 17
3.Whole bowel irrigation
a. Saline Keighley 83
Weidema and Van den 86
Bogard 90
Beck & Fazio
b. Mannitol 82
Keighley 75
Beck & Fazio
c. PEG 92
DiPalma et al 90
Beck & Fazio
d. Picolax 46
Takada et al 80
Vanner et al
e. Sodium phosphate 84
Lee et al
B. ANTIMICROBIAL BOWEL PREPARATION
Elective colorectal operations are classified as clean contaminated operative procedures. Because
these procedures always result in bacterial contamination of the operative site, antibiotics are
desirable. Without antimicrobial preparation the rate of wound infection in elective colorectal
operations is known to vary between 30-60%24. MBP alone does not reduce colonic bacterial
concentration and hence does not decrease the postoperative septic complications.
The rationale for perioperative administration of antibiotics is to either reduce the colonic bacterial
concentration or to obtain sufficient levels of these drugs during perioperative period. This can be
achieved by oral or intravenous administration of antibiotics. Since the aerobic species of E.coli and
anaerobic species of Bacteroides fragilis are the most frequently involved organisms, targeting these
decreases postoperative wound infection rate significantly24, 25.Oral administration of either
erythromycin and neomycin or metronidazole and neomycin have been found to be effective in
reducing the postoperative septic complications24, 25. These drugs are to be given at 1 pm, 2pm and
11pm on the day before surgery, for surgery scheduled at 8 am in the next morning.
Antimicrobials can also be administered systemically. As highest concentration of these is desirable at

the time of incision, they are administered shortly before surgery. A second generation cephalosporin,
active both against aerobic and anaerobic organism, is favoured widely. Whether antimicrobial bowel
preparation should be oral, systemic or both, is still a controversial issue. Most surgeons use a
combination of oral and systemic antibiotics and have found favorable results26 (Table 2).
323
TABLE 2: Comparison of wound infection rate in elective colorectal operations in various studies after
antimicrobial bowel preparatory techniques
Authors Wound infection rate (%)
Oral * Parenteral# Combined oral &

Parenteral
1. Condon et al (1983) 8 - 6
2.Coppa et (1983) 18 - 7
3. Portnoy et al(1983) 27 - 2-5
4. Lau et al (1988) 29 - 11
5. Petrelli et al(1988) 3 - 0
6.Playforth et al(1989) 28 - 14
7. Hall et al (1989) - 15 -
8. Periti et al (1989) - 9-11 -
9. Schotez et al (1990) 15 - 5
10.Stellato et al (1990) 7 4 6
11.Skipper et al (1992) - 14 -
12. Morris (1993) - 6-17 -
13. Santos et al(1994) - 17 -
14. Mechhia( 2000) - 7-11 -
15. Rau et al (2000) - 4-18 3
16. Lewis (2002) - 17 5
* Oral drugs used- Erythromycin and Neomycin or Metronidazole and Neomycin.
# Parenteral drug used commonly- A second generation cephalosporin.
ADVANTAGES AND DISADVANTAGES OF PRE-OPERATIVE BOWEL PREPARATION

TYPE ADVANTAGES DISADVANTAGES
1.Mechanical 1. Makes bowel less bulky, hence improved 1. May induce fluid and
Bowel handling during surgery. electrolyte disturbances.
Preparation 2. Helps in keeping the operative field clean. 2. Problems with palatability,
3. Necessary in cases where intraoperative patient acceptance, cost and
palpation or colonoscopy is required. hence, compliance.
4. Necessary where low or very low 3. Increased chances of
anastomoses are made. anastomotic dehiscence.
5. Needed while operating on retroperitoneum 4. Increased chances of wound
through transperitoneal route. infections.
2. 1. Decreased wound infections. 1. Hypersenstivity reactions to
Antimicrobial drugs.
preparation 2. Systemic absorption of
neomycin may cause ototoxicity
and nephrotoxicity.
3. Neomycin has damaging
effect on intestinal villi, may
cause malabsorption syndrome
with diarrhea and steatorrhea.
3. Marked suppression of gut
flora may invite opportunistic
fungal (candida) infections.
4. Erythromycin may cause
abdominal pain by increasing
gut motility.
5. Metronidazole may induce
anorexia, metallic taste and
abdominal cramps.
324
SUMMARY
In a critical retrospective view, the idea of bowel preparation essentially seems to have been
promoted by the belief that the absence of stool in the intestine must be advantageous. This concept
is based on traditional and personal empiricism and usually not evidence based.
Recent randomised controlled trials have not demonstrated any conclusive benefit from this
procedure. Regarding anastomotic dehiscence and surgical infectious complications, current clinical
research offers no evidence to support the claim that MBP should be performed prior to colorectal
surgery. On the contrary, all the most recent meta-analyses revealed a significant increase of risk for
anastomotic dehiscence after MBP. Even the rate of surgical infectious complications such as wound
infections, abscesses and peritonitis could not be lowered by preoperative MBP. Furthermore,
potential side-effects such as electrolyte and hydration disorders, patient discomfort, medical and
nursing labor and - as a consequence - costs have gone up. With the improvement in surgical
technique together with the use of more effective prophylactic antibiotics, it is possible that MBP
would no longer be necessary. Rather, prophylactic antibiotics play a significant role in colorectal
surgery and prevention of wound infection.
Despite this, most surgeons still use MBP26. Most surgeons would prefer to comply with handling a
clean and unloaded bowel during surgery although it may not be necessary to clean every speck of
feces from bowel.
Accordingly, the previous guidelines have been revised as follows:

Mechanical bowel preparation is not indicated in elective colorectal operations unless there are
anticipated problems with fecal loading that might create technical difficulties with the procedure. e.g.
laparoscopic surgery, low rectal cancers. Prophylactic antimicrobials have important role in preventing
wound infections in colo-rectal surgery.
References
1. Beck DE, Harford FJ, DiPalma JA. Comparison of cleansing methods in preparation for colonic surgery. Dis Colon
Rectum 1985;28:491-5.
2. Zmora O, Wexner SD. Bowel preparation for colonoscopy. Clin Colon Rectal Surg 2001;14:309-15.
3. Hewitt J, Rigby J, Reeve JWhole gut irrigation in preparation for large bowel surgery. Lancet1973;2:337-340.
4. Irvin TT, Goligher JC. Aetiology of disruption of intestinal anastomoses. Br J Surg 1973;60:461-464.
5.Bucher P, Mermillod B, Gervax P, Morel P. Mechanical bowel preparation for elective colorectal surgery- a meta-
analysis. Arch Surg 2004;139:1359-1364.
6. Guenega KF, Matos D, Castro AA, Atallah An,Wille-Jorgenson P. Mechanical bowel preparation for elective
colorectal surgery. Cochrane database systemic review2005;1:CDOO 1544.pub 2.
7. Bucher p, Gervaz P, Soravia C, Mermillod B, Erne M, Morel P. Randomized clinical trial of mechanical bowel
preparation versus no preparation before elective lef sided colorectal surgery. Br J Surg 2005;92:409-414.
8. Slim K, VicoutE, Panis Y, Chipponi J. Meta-analysis of randomized clinical trials of colorectal surgery with or
without mechanical bowel preparation. Br J Surg 2004;91:1125-1130.
9. Davis GR, Santa Ana CA, Morawski SG, Fordtran JS. Development of a lavage solution with minimal water and
electrolyte absorption or secretion. Gastroenterology 1980;78:991-5.
10. Dipalma JA, Brady CE III, Stewart DL, et al. Comparison of colon cleansing in preparation for colonoscopy.
Gastroenterology 1984;86:856-60.
11. Ernstoff JJ, Howard DA, Marshall JB et al. A randomized blinded critical trial of a rapid colonic lavage solution
compared with standard preparation for colonoscopy and barium enema. Gastroenterology 1983;84:1512-6.
12. Thomas G, Brozisky S, Isenberg JI, Patient acceptance and effectiveness of a balanced lavage solution versus the
standard preparation for colonoscopy. Gastroenterology 1982;82:435-37.
13. Froehlich F, Fried M, Schnegg JM, Gonvers JJ. Palatability of a new solution compared with standard polyethylene
glycol solution for gastrointestinal lavage. Gastrointest Endosc 1991;37:325-8.
14, Frommer D. Cleansing ability and tolerance of three bowel preparations for colonoscopy. Dis Colon Rectum
1997;40.
15. Hsu CW, Imperiale TF. Meta-Analysis and cost comparison of polyethylene glycol lavage versus sodium phosphate
for colonoscopy preparation. Gastrointest Endosc 1998;48:276-82.
16. Chang KJ, Erickson RA et al. Per-rectal pulsed irrigation versus per-oral colonic lavage for colonoscopy
preparation: a randomized, controlled trial. Gastrointest Endosc 1991;37:444-8.
17. Weidema WF, Van den Boggard AEJM. Whole gut irrigation and antimicrobial prophylaxis in elective colorectal
surgery [thesis]. Utrecht, Netherlands: Bohn, scheltema & Holkema, 1984.
18. Keighley MRB. A clinical and physiological evaluation of bowel preparation for elective colorectal surgery. World J
Surg 1982;6:464-70.
19. Beck DE, Fazio VW, Jagleman DG. Comparison of oral lavage methods for preoperative colonic cleansing. Dis
Colon Rectum 1986;29:699-703.
20. Hares MM, Alexander-Williams J. The effect of bowel preparation on colonic surgery. World J Surg 1982;6:175-181.
21. Keighley MRB, Taylor EW, Haress MM. Influence of oral Mannitol bowel preparation on colonic microflora and the
risk of explosion during endoscopic diathermy. Br J Surg1981;68:554-556.
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22. Zanono CE, Bergamini C, Bertocini M. Whole gut lavage for surgery. A case of intraoperative colonic explosion
after the administration of mannitol. Dis Colon Rectum 1982;25:580-581.
23. Bigand MA, Gaucher P, Lasalle C. Fatal colonic explosion during colonoscopic polypectomy. Gastroenterology
1979;77:1307-1310.
24.Clarke JS, Condon RE, Barley JG. Preoperative oral antibiotics reduce septic complications of colon operations.
Ann Surg 1977;186:251-259.
25. Matheson DM, Arabi Y, Baxter-Smith D. Randomized multicentric trials of oral bowel preparation and
antimicrobials for elective colorectal operations. Br J Surg 1978;65:597-600.
26. GordanPH, Schouten WR. Preoperative and postoperative management. In: Principles and practice of surgery for
rd
the colon, rectum and anus,3 Ed. 2007
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Premalignant Conditions of the Colon and Rectum
Dr. Vijay Arora
A premalignant condition is a lesion which exists and leads to a higher incidence of malignant change.
An adenoma usually precedes the development of colorectal cancer and a graphic adenoma –
carcinoma sequence has been well documented
Patients with two synchronous carcinomas have 75% associated adenomas. Patients with adenomas
in association with carcinoma have higher chance of developing a new carcinoma after surgery than
those who have no adenoma.
Epidemiological data also supports the adenoma – carcinoma sequence in that both are more
prevalent in a westernized society in which a low fiber high meat diet is typical.
Experimental carcinogens which produce colo-rectal cancers are also known to induce adenoma
formation.
Histological studies of carcinomas show elements of benign adenomas within the tumor. Similarly
there is a 3-4% incidence of carcinoma in apparently benign adenomas.
In patients who do not have adenomas, the process of malignant transformation of epithelial cells is
through the development of dysplasia.
The epithelial cells may show an increase in mitotic figures that may form several layers and their
nuclei may become pleomorphic, with loss of polarity.
Any invasion of these abnormal epithelial cells through the muscularis mucosal to enter the
submucosa constitutes malignant transformation.
Dysplasia may be mild, moderate or severe. Severe dysplasia is often termed ―carcinoma in situ‖ by
some pathologists. The difference must be stressed.
Carcinoma in situ in an adenoma still confined to mucosa is not a cancer. Approx 60% of adenomas
show mild dysplasia, 30% exhibit moderate dysplasia and 10% show severe dysplasia. The incidence
of malignancy in adenomas is 3-4%
327
A polyp is an abnormal elevation from an epithelial surface. It may be pedunculated or sessile. They
may be flat or villous. They may be neoplastic or inflammatory. They may be inherited, symptomatic
or asymptomatic, single or in clusters or occupy the whole mucosa.
This is then described as polyposis syndrome. These are the main premalignant conditions, and are
classified as following:-
Neoplastic
- Familial adenomatous polyposis
- Turcot‘s syndrome
- Lymphosarcomatous (lymphomatous) polyposis
- Leukaemic polyposis
Inflammatory
- Ulcerative colitis
- Crohn‘s disease
- Other inflammatory polyposis: amoebiasis schistosomiasis, eosinophilic, granulomatous
polyposis, diffuse histoplasmosis
Hamartomatous
- Juvenile polyposis
- Peutz-Jeghers syndrome
- Neurofibromatous polyposis
- Lipomatous polyposis
- Cronkhite –Canada syndrome
- Cowden‘s disease
Unclassified
- Metaplastic polyps
- Pneumatosis cystoids intestinalis
(See Appendix I)
An important entity is the hereditary non polyposis colon cancer. Mere presence of these conditions is
not indicative of malignancy and a strategy of finding the individual who is going to develop malignant
change is by risk assessment. Factors may have to be added are age, family history and personal
history
Average risk
- Age >=50 yrs
- No history of adenoma
- No history of inflammatory bowel disease
- Negative family history
Increased risk
- Personal history
o Adenoma
o Colorectal cancer
o Endometrial / ovarian cancer <age 60 years
o Inflammatory bowel disease
- Positive family history
o A first degree relative with colorectal cancer or adenoma or two second degree
relatives (related to each other) with colorectal cancer
o Clustering of colorectal cancer or HNPCC related cancers in the family
- Hereditary high risk
o Colorectal cancer at age <50 yrs or clustering of colorectal cancer or HNPCC related
cancers in the family, or personal or family history of polyposis.
o Polyposis syndromes
o HNPCC
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Screening programs for risk assessment - Colorectal screening for persons at Average risk
Current recommendations are : -
 FOBT every year
 Sigmoidoscopy every 5 year
 Colonoscopy every 10 year
 Positive FOBT is an indication for colonoscopy
 Polypectomy or biopsy is done when a sigmoidoscopy or colonoscopy is done
There is a demonstrated reduction of 45-79% of mortality in case controlled studies
Polyps seen on colonoscopy may be : -

- Hyperplastic polyps – not usually associated with increased risk unless concomitant
adenomas are present.
- Adenoma – Biopsy proven adenoma, tubular adenoma or serrated adenoma should be
removed or biopsied. Follow up strategies are now well defined.
Alternative Methodology for screening

The methodology of screening is by performing various tests to assess and identify early changes
which may indicate malignancy.
1. Fecal occult blood test

a. Guaiac based non rehydrated technology
b. Immunochemical methods
Two samples on prescribed diet. DRE is not a proven method and fecal occult blood taken DRE
sample is not recommended.
2. Double Contrast Barium Enema – can be performed every 5 years in a patient with average
risk. Limited sensitivity and specificity. Experience is decreasing
3. Computed Tomographic (CT) Colonography or virtual colonoscopy is evolving as a very

promising technique for colorectal screening for polyps larger than 9 mm very specific but
wide range of sensitivity 55 to 94%
4. Stool DNA Test – Emerging non-invasive diagnostic tool. It involves detection of molecular
alterations in fecal DNA using single target DNA marker involving K-ras oncogene mutations.
Multitarget DNA stool testing is under trial
Individuals at Increased Risk

Personal history of adenoma – Increased risk for developing recurrent adenomas and
colorectal cancer.
Surveillance is recommended for patients with adenomas following colonoscopy and complete
polypectomy. Surveillance schedule is related to number of adenomatous polyps size and
histology.
Low risk – tubular, 2 or fewer, less than 1 cm – repeat colonoscopy within 5 years.
Increased risk – size >1 cm, villous histology or high grade dysplasia, carcinoma in situ.
Recommended repeat colonoscopy every 3 years. Individuals with 10 or more adenomas should
be evaluated for a polyposis syndrome. Large sessile polyps have a high rate of recurrence due
to residual adenoma tissue. If malignant polyp is found then follow up surgery is needed.
Personal history of colorectal cancer

Patients who have undergone colonic resection with a curative intent are at increased risk for
recurrent adenomas and cancer in the 4-5 years. Surveillance is intensive with colonoscopy at 1
year. If normal, repeat in 2-3 years. If adenoma is found, it should be followed or removed as per
guidelines.
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Periodic endoscopic evaluation of the rectal anastomosis to identify local recurrence. Women with
a personal history of endometrial or ovarian cancer prior to 50 years are at high risk and should
be subjected to colonoscopic surveillance.
Inflammatory bowel disease

- Ulcerative colitis
- Crohn‘s disease
Patients of IBD with symptoms of pancolitis for 8 or more years are at increased risk for colorectal
cancer.
Screening by colonoscopy should be started at 8-10 years after the onset of symptoms by an
endoscopist. Clinically quiescent stage necessitates multiple four quadrant biopsies every 10 cm.
Strictures should be evaluated using both biopsy and brush cytology. Any mass often called
dysplasia associated lesions should be endoscopically removed.
Interpretation of data is often difficult. Repeated low grade dysplasia or high grade dysplasia
necessitates prophylactic proctocolectomy with ileoanal anastomosis
Family history
Single most important risk factor. Detailed family history from
1st degree relatives – parents, siblings, off springs.
2 degree relatives – aunts, uncles, grandparents, great grandparents
Additional relatives – cousins, nieces and nephews
Individuals who have a first degree relatives with a colorectal cancer prior to 50 years of age or
two first degree relatives with colorectal cancer at any age or clustering of HNPCC or polyposis.
Hereditary evaluation and screening should be started as per guidelines.
Inherited Colon Cancer

Defined inherited syndromes
- Hereditary non-polyposis colorectal carcinoma. HNPCC also known case Lynch syndrome
- Familial adenomatous polyposis (FAP)
- MYH-associated polyposis (MAP)
Peutz-jeghers syndrome
Juvenile polyposis
Nonsyndromic familial colorectal cancer
Have genetic susceptibility
Hereditary Nonpolyposis Colon Cancer (HNPCC) is the most common form of a genetically
determined colon cancer predisposition.
Caused by mutations in DNA mismatch repair (MMR) agenes (MLH1, MSH2, MSH6, PMS2). Lifetime
risk of colorectal cancer is 80%. Surveillance has been shown to reduce the risk. Associated cancer
than can occur – endometrial, ovarian, gastric and urethral.
Familial Adenomatous Polyposis is an autosomal dominant condition characterized by hundreds to

thousands of polyps (carpeting). Life time risk of cancer in classic FAP is 100% by age 50.
Early screening and Colectomy or proctocolectomy at the onset of polyposis is recommended.
Genetic listing of all members of family to identify mutated gene for adenomatous polyposis Coli
(APC), located on 5g21 chromosome. Individuals with a personal history of FAP are more at risk than
persons with a family history of FAP.
Other entities include suspected colon cancer syndromes such as

Muir-Torre
Turcot
Pentz-jaghens
Juvenile polyposis
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Evaluation of inherited colorectal cancer
- Detailed family history
- Define syndrome specific feature
- Pathologic verification
- Associated examinations to detect
o Osteomas
o Odontoma
o Supernumerary teeth
o Epidermoid cysts
o Desmoids
o Duodenal and small bowel adenomas
Molecular workup for effective screening in HNPCC

- Microsatell Instability Analysis (MSI)
- Immunohistochemical (IHC) testing
Genetic testing - Genetic screening for MSI positive patients and the siblings and children to detect
mutation carriers
Familial Adenomatous Polyposis (FAP)

Presence of over 100 polyps, particularly with a family history
Family members are diagnosed at adolescence through genetic testing or sigmoidoscopy screening in
the second decade. Prophylactic proctocolectomy indicated in the second decade. Fundic gland
polyps occur in most FAP patients.
Thyroid cancer is a lifetime risk at 2% with female predomination
Attenuated FAP - Later onset of disease and fewer adenomas – less than 100 onset of colorectal
cancer is delayed – after age 40.
Surgical options in FAP

1. Total proctocolectomy with ileal pouch anal anastomosis (IPAA)
2. Total abdominal Colectomy with ileorectal anastomosis (IRA)
3. Total proctocolectomy with Ileostomy (TPC)
Chemoprevention
Non steroidal anti-inflammatory drugs (NSAIDS) have been shown to reduce the incidence and
recurrence of colorectal adenomas. Cyclooxygenase-2 (Cox-2) inhibitors have been shown to be
over-expressed in colorectal adenomas and cancers and are undergoing trials (Pre SAP). Prevention
of colorectal sporadic adenomatous polyps (Pre SAP)
Duodenoscopy in FAP
Duodenal adenomas occur in over 90% of patients with FAP. Staged from I to IV with increasing risk
of malignancy. Surveillance and endoscopic treatment or mucosectomy may be needed to avert
surgery.
Non-syndrome Hereditary Colon Cancer – risk based on a familial susceptibility that is not FAP and
not HNPCC is also being considered
MYH Associated Polyposis (MAP) – caused by biallelic germ line mutation in Mut Y Human
Homolog (MYH) gene and reported in approx 0.4% of colorectal cancer patients. To be treated same
as FAP but expressed at later age.
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Carcinoma anal canal
Dr. A.K. Bahadur, Saurabh Kumar
ANATOMY
The anal region lies at a transition between endoderm and ectoderm and is commonly divided into the
anal canal and the perianal skin. The anal canal extends from the rectum to the perianal skin and is 3
to 4 cm long. The superior margin is at the level of the palpable upper border of the anal sphincter and
puborectalis muscle of the anorectal ring.The extent of the perianal skin is not defined but is usually
considered to encompass a 5-cm radius around the anal verge.
Four different types of epithelium
The perianal skin is similar to hair- and glandular-bearing skin elsewhere and becomes puckered and
pigmented near the anal verge.
At the verge it blends with the pale mucosa of the distal canal, which is lined by modified squamous
epithelium lacking skin appendages.
Just below the dentate or pectinate line, the most visible landmark in the canal and formed by the
lower end of the anal valves, the squamous epithelium blends with a transitional epithelium that has
rectal, urothelial, and squamous features.
The purplish-red transitional zone extends proximally for approximately 1 to 2 cm, where it merges
with the pink glandular mucosa of the rectum.
The veins of the anal canal communicate with the portal and the systemic venous systems.
The lymphatics of the anal region flow to three lymph node systems.
1. Lymph from the perianal skin and the canal distal to the dentate line drains mainly to the
superficial inguinal nodes, with some inconstant communications to the femoral or
external iliac nodes.
2. Lymph from about and above the dentate line flows with that from the distal rectum to the
internal pudendal, hypogastric, and obturator nodes of the internal iliac system.
3. The drainage of the proximal canal is to the perirectal and superior hemorrhoidal nodes of
the inferior mesenteric system. Numerous lymphatic connections exist between the
various levels of the anal canal.
EPIDEMIOLOGY
Anal cancers are approximately one-tenth as common as cancers of the rectum.
Cancers arise in the canal three to four times more frequently than in the perianal skin. The median
age at diagnosis is from 60 to 65 years.
Most annual incidence rates lie in the range 0.5 to 1.0 per 100,000 among women and 0.3 to 0.8 per
100,000 among men1.
Perianal cancers occur with approximately equal frequency in both sexes.
PATHOLOGY
Squamous Cell 63%
Transitional Cell 23%
Adenocarcinoma 7%
Melanoma 2%
Basal Cell Carcinoma 2%
Paget‘s Disease 2%
ETIOLOGY
Evidence has been shown that sexually transmissible agents, such as human papillomavirus (HPV),
immunosuppression, and tobacco smoking, are of particular importance. A number of similarities have
332
been noted between squamous cancers of the anal region and of the uterine cervix, vagina, and
vulva, the epithelia of which have common features and embryologic origin. HPV type 16 has a
particularly high risk of association with anal squamous cancer, as have, to a lesser extent, types 18,
31, 33, 35, and others. These high-risk HPVs (hrHPVs) have been found in approximately 85% of
anal squamous cancers in some series, the proportion being partly dependent on the sensitivity of the
assay.2,3
In a series of 386 patients, 86% of whom had invasive cancers, hrHPV were identified in 90% of the
anal squamous cancers in women and in 63% of those in men.3 Squamous cancers arising in the anal
canal were hrHPV positive in 92%, compared to 64% in the perianal skin.3 Because of this
discrepancy, it has been suggested that there may be another pathway, not mediated by HPV, by
which perianal squamous cancer can develop.3
The identification of a twofold increase in the risk of anal cancer in unmarried men in register-based
studies first suggested that sexual behavior might affect the risk of anal cancer. Never-married status
among men was assumed to include a relatively high proportion of homosexual men,
The ability to prevent or eliminate viral infection is reduced by compromise of cell-mediated immunity.
Iatrogenically immunosuppressed organ transplant patients have an increased risk of several types of
malignancy, including anogenital squamous cancers. Anal cancer is not at this time an AIDS-defining
neoplasm.
Although some investigators have identified an incidence of anal squamous cancer in HIV-positive
homosexual men approximately double that in those who are HIV negative4, others have found little, if
any, difference.5 Whether immunosuppression is iatrogenic or due to HIV infection, those affected
have increased rates of anogenital HPV infection, higher progression rates from normal epithelium to
AIN and from low to higher-grade AIN, and lower rates of clearance of HPV and regression from
abnormal to normal epithelium.
Although tobacco smoking is associated with an approximately fivefold increase in risk in several
case-control studies5, it has been suggested that these studies might have been confounded in part
by unreported male homosexuality5. It has been postulated that an antiestrogenic action of tobacco
products may contribute to anogenital squamous carcinogenesis6.
Benign anal conditions such as fistulas, fissures, and hemorrhoids do not appear to predispose to
cancer, although fissures may facilitate the access of hrHPV to basal epithelial cell layers.
NATURAL HISTORY
Squamous cell cancers of the anal region, especially the canal, are believed to be preceded by high-
grade AIN in most instances. However, it has been estimated that no more than 1% of patients with
AIN develop invasive cancer per year,
Squamous cell cancers of the anal canal are characterized by local extension of the primary tumor
and lymphatic spread rather than by hematogenous metastases. The primary cancers grow along the
length and circumference of the canal and invade the sphincter muscles and perianal connective
tissues quite early.
Cancer extends beyond the canal into the rectum or perianal skin, or both, in approximately half the
cases. Deep invasion of the anovaginal septum occurs in approximately 10%, but invasion of the
prostate is very uncommon.
Lymphatic spread also occurs early. The regional nodes for the anal canal are now considered to be
the perirectal, internal iliac, and inguinal nodes. The nodes of the rectosigmoid and sigmoid vascular
arcades are regarded as distant metastatic sites. Based on late relapse rates, inguinal node
metastases were present subclinically in a further 10% to 20%.
Nodal metastases were found with 30% of cancers confined to the sphincter muscles, and with 60%
of those that had extended to extrasphincteric tissues or were poorly differentiated. Although some
authors found that the rate of lymph node metastases correlated to increasing size of the primary
333
cancer,7 others observed that, for primary cancers greater than 2 cm in size, increasing size was not a
reliable predictor of metastasis to nodes.24
Extrapelvic metastases at the time of first presentation are not common and are identified in fewer
than 5%.8 Metastases occur as the sole site of failure in approximately 10% after successful treatment
of the primary cancer and regional nodes. Metastases may occur via the portal or systemic venous
systems or via lymphatics. They are found most frequently in the liver, lungs, and extrapelvic lymph
nodes and occasionally in bone, skin, brain, and other sites.
Relapse after treatment directed principally to the pelvis, and with only limited systemic therapy, is
more common at the site of the primary tumor and regional nodes than outside the pelvis. The risk of
local-regional relapse in current practice is up to approximately 30% and extrapelvic failure up to
approximately 20%.9,10,11 The overall 5-year survival rates in population-based registries, generally
reflecting treatment practices before current radiation and chemotherapy combinations, are on the
order of 55%.8
Perianal squamous cancers tend to grow locally. They may extend into the anal canal. When there is
doubt about the site of origin, it is conventional to classify the cancer as arising in the canal. The most
common site of spread is to the ipsilateral inguinal nodes, which are reported to be abnormal in from
5% to 20%. Extrapelvic metastases are uncommon and are usually associated with poorly
differentiated cancers, inguinal metastases, or uncontrolled and extensive primary tumors. Overall 5-
year cause-specific survival rates usually exceed 80%.
PROGNOSTIC FACTORS
Among the many cancer, patient, and treatment factors studied, the anatomic extent of an anal cancer
provides the most useful and reproducible prognostic information.12,13 Extrapelvic metastases carry
the worst prognosis.14 In the absence of distant metastases, the size of the primary tumor is the most
useful predictor of local control, preservation of anorectal function, and survival.10 Spread to regional
lymph nodes is an adverse factor for survival in most series,10,15 and in some series,15 but not all,16 for
control of the primary tumor.
Age and performance status have each been considered prognostic, but case selection affects
interpretation of many reports. Hemoglobin levels of 10 g/L or less at presentation have been
correlated with lower local control and survival rates.17 Serum markers such as carcinoembryonic
antigen and squamous cell carcinoma antigen have not provided consistent results when evaluated
as aids to diagnosis or monitoring of response. In HIV-positive patients high viral load, low lymphocyte
CD4+ counts, and AIDS have been prognostic of poor local tumor control and survival and, in some
series, of impaired tolerance of radiation and chemotherapy.18,19
TREATMENT
Radiotherapy
 Areas to be included
Primary tumor
Inguinal lymph nodes
Iliac lymph nodes.
Para rectal nodes
 Techniques
Whole pelvis technique
Posterior pelvis technique
 Whole- Pelvis pelvis

Patient position- Supine or prone.
Upper border- Lumbosacral junction.
Lateral border- Wide to include inguinal and external iliac nodes.
Inferior border- 3 cm distal to the lower most extent of tumor.
 Posterior pelvis technique

Posterior pelvis tissues and inguinal nodes treated discontinuously.
334
Inguinal nodes are treated using electron beams
Anal canal and posterior pelvis can be treated using three field arrangement.
 Radiation dose
Radiotherapy alone
40-45Gy in 4-5 weeks + 15-20Gy in 2 weeks as boost.
Concurrent with chemotherapy
45Gy/25#/5weeks + 5.4/3# as boost to reduced volume.
 Interstitial brachytherapy

To boost the tumor site
20-25Gy at 85% isodose curve
Semicircular implant encompassing 2/3rd of canal circumference.
Stainless steel needles placed at 1cm distance and .5cm below mucosa.
 Chemotherapy Regimen

5-FU 750mg/m2 IV D1-D5 & D29-33
Mitomycin 10-15mg/m2 IV D1
5-FU 800mg/m2 IV D1-4

Cisplatin 80mg/m2 IV D1
Stage wise management of ca anal canal as recommended by NCI
Stage-0- Surgical resection is used for treatment of lesions of the perianal area not involving the anal
sphincter (approach depends on the location of the lesion in the anal canal).
Stage I- Small tumors of the perianal skin or anal margin not involving the anal sphincter may be
adequately treated with local resection.
All other stage I cancers of the anal canal that involve the anal sphincter or are too large for
complete local excision are treated with external-beam radiation therapy with or without
chemotherapy.
Chemotherapy with fluorouracil and mitomycin combined with primary radiation therapy
appears to be more effective than radiation therapy alone. The optimal dose of radiation with
concurrent chemotherapy is under evaluation.
Selected tumors are also suitable for interstitial irradiation.
Radical resection is reserved for residual or recurrent cancer in the anal canal after
nonoperative therapy.
Alternately, salvage chemotherapy with fluorouracil and cisplatin combined with a radiation
boost may avoid a permanent colostomy in selected patients with small amounts of residual
tumor following initial nonoperative therapy.
Interstitial iridium-192 after external-beam radiation may convert some patients with residual
disease into complete responders.
Stage-II-Small tumors of the perianal skin or anal margin not involving the anal sphincter may be
adequately treated with local resection.
All other stage II cancers of the anal canal that involve the anal sphincter or are too large for
complete local excision are treated with external-beam radiation therapy plus chemotherapy.
Chemotherapy with fluorouracil and mitomycin combined with primary radiation therapy
appears to be more effective than radiation therapy alone. The optimal dose of radiation with
concurrent chemotherapy is under evaluation.
335
Selected tumors are also suitable for interstitial irradiation.
Radical resection is reserved for continued residual or recurrent cancer in the anal canal after
Alternately, salvage chemotherapy with fluorouracil and cisplatin combined with a radiation
boost may avoid a permanent colostomy in selected patients with small amounts of residual
tumor following initial nonoperative therapy.
Stage-IIIA- Treatment as for stage I and II disease, using radiation therapy plus chemotherapy.
Radical resection is reserved for continued residual or recurrent cancer in the anal canal after
StageIIIB- Radiation therapy plus chemotherapy (as described for stage II) with surgical resection of
residual disease at the primary site (local resection or abdominoperineal resection) and
unilateral or bilateral superficial and deep inguinal node dissection for residual or recurrent
tumor.
Stage-IV Patients in this stage should be considered candidates for clinical trials. There is no
standard chemotherapy for patients with metastatic disease. Palliation of symptoms from the
primary lesion is of major importance.
SEQUELAE
Severe or moderately severe acute anoproctitis and perineal dermatitis occur in approximately one-
third of those who receive concurrent 5-FU–containing chemotherapy and radiation doses of about 30
Gy in 3 weeks, and in approximately one-half to two-thirds of those treated with doses of 54 to 60 Gy
in 6 weeks. Most large studies of radiation and concomitant chemotherapy have reported up to
approximately 2% mortality, usually as a result of sepsis, not always associated with neutropenia, or
of severe anoproctitis, diarrhea, and electrolyte disturbance. Considerable progress has been made
by refining radiation techniques to reduce the risk of late complications that require surgery from the
5% to 15% reported in some early series.20 Side effects of lesser severity, but which affect quality of
life adversely, are common and include urgency and frequency of defecation, perineal dermatitis,
dyspareunia, and impotence.21,22,23 These side effects are managed medically, although with limited
success.21 The severity of moderate-grade acute and late toxicity is influenced by radiation technique
and dose-time factors.20
Although chemoradiation is the preferred initial treatment, some patients have contraindications to
chemotherapy or refuse drug therapy. These individuals can be offered radical radiation alone as
initial treatment, with reasonable expectations of cure and preservation of function.
Radical resection of intermediate-stage primary anal canal cancer is reserved for patients who cannot
tolerate radiation therapy or chemoradiation or who are incontinent due to irreversible damage of the
sphincters or an anovaginal fistula. Patients who have had prior pelvic radiation treatment (most
frequently for carcinoma of the cervix) generally cannot be retreated and are managed surgically.
Active inflammatory bowel disease affecting the rectum or anal region may be a relative
contraindication to pelvic radiation, although most patients in whom inflammatory bowel disease is
quiescent tolerate radiation and chemotherapy. The most common indications for radical resection are
failure of chemoradiation or radiation and, less frequently, complications of the initial treatment.
RESIDUAL DISEASE
Suspected residual cancer should be confirmed by biopsy. Residual masses after radiation or
chemoradiation may take several months to regress fully.10,24 Frequent examination by an
experienced observer is desirable, including, if necessary, examination under anesthesia, to detect
recurrence early and forestall progression to technical unresectability. The development of a hard-
edged ulcer after previous healing, an enlarging mass, or increasing pain at the primary tumor site
should raise suspicion of recurrence.
336
The results of salvage abdominoperineal resection or composite resection to include adjacent
structures vary widely, with survival rates from as low as 0% to better than 50%. Strictly, all local
recurrences are due to residual cancer. Criteria for attempting surgical salvage were stated
infrequently, and factors assessable preoperatively that are prognostic of long-term control have not
been established. Decision making in this patient group is complex and should include
multidisciplinary consultation. In particular, the need for reconstructive surgery to close defects in
irradiated pelvic tissues should be considered. It can be concluded that salvage surgery offers a
potential for long-term local control and survival in roughly one-third to one-half of the patients fit for
surgery who do not have clearly unresectable cancer or known extrapelvic disease. Palliative surgery
can be offered according to the circumstances of individual patients.
Carcinoma anal canal and HIV
Patients who are HIV positive are at increased risk for development of AIN and of squamous cancers
of the anal canal or perianal skin. Local excision is the treatment of first choice for AIN or early stage
invasive cancer. Treatment by radiation alone, or combined modality regimens, has been effective in
several small groups of HIV-positive patients with more extensive cancer. HIV-infected patients are at
increased risk of toxicity, particularly in the perineal skin and anorectal mucosa, when exposed to
therapeutic doses of radiation, either alone or combined with chemotherapy. Although the
mechanisms for this unpredictable hypersensitivity are not known, the risk of increased toxicity and of
lower probability of control of the anal cancer appears to be greater in patients with a lymphocyte
CD4+ count less than 200/ L at the time of starting treatment, or with AIDS.18,25 The limited data
available suggest that HAART does not reliably reduce the severity or incidence of cancer treatment–
related toxicity.26 Complete primary anal cancer remission rates with either radiation or radiation plus
chemotherapy on the order of 70% have been described, comparable to or marginally inferior to those
in non–HIV-infected patients. It is difficult to obtain reliable data on long-term local control or cancer
relapse patterns.25
Several reports suggest that it is not necessary to alter standard protocols of radiation or
chemotherapy in anticipation of possible toxicity, but modification should be based on the severity of
side effects observed in each patient.18,25 Some patients decline cytotoxic chemotherapy because of
their concern that depletion of marrow reserve may impair their ability to tolerate HAART. Radiation
alone can be offered to such patients. Radical surgery should be considered for those who cannot
tolerate radiation with or without chemotherapy or if such treatment fails.
References
1. International Agency for Research on Cancer. Cancer incidence in five continents. Lyon, France, 1997.
2. Zbar AP, Fenger C, Efron J, et al. The pathology and molecular biology of anal intraepithelial neoplasia:
comparisons with cervical and vulvar intraepithelial carcinoma. Int J Colorectal Dis 2002;17:203.
3. Frisch M, Fenger C, van den Brule AJ, et al. Variants of squamous cell carcinoma of the anal canal and perianal
skin and their relation to human papilloma virus. Cancer Res 1999;59:753.
4. Goedert JJ, Cote TR, Virgo P, et al. Spectrum of AIDS-associated malignant disorders. Lancet 1998;351:1833.
5. Frisch M. On the etiology of anal squamous carcinoma. Dan Med Bull 2002;49:194.
6. Frisch M, Goodman MT. Human papilloma virus–associated carcinomas in Hawaii and the mainland U.S. Cancer
2000;88:1464
7. Frost DB, Richards PC, Montague ED, et al. Epidermoid cancer of the anorectum. Cancer 1984;53:1285.
8. Myerson RJ, Karnell LH, Menck HR. The national cancer data base report on carcinoma of the anus. Cancer
1997;80:805.
9. Boman BM, Moertel CG, O'Connell M, et al. Carcinoma of the anal canal: a clinical and pathological study of 188
cases. Cancer 1984;54:114.
10. Cummings BJ, Keane TJ, O'Sullivan B, et al. Epidermoid anal cancer: treatment by radiation and 5-fluorouracil
with and without mitomycin C. Int J Radiat Oncol Biol Phys 1991;21:1115.
11. UKCCCR Anal Canal Cancer Trial Working Party. Epidermoid anal cancer: results from the UKCCCR randomized
trial of radiotherapy alone versus radiotherapy, 5-fluorouracil and mitomycin C. Lancet 1996;348:1049.
12. Cummings BJ. Anal cancer. In: Gospodarowicz MK, Henson DE, Hutter RV, et al., eds. Prognostic factors in
cancer, 2nd ed. New York: Wiley-Liss, 2001:281.
13. Fenger C. Prognostic factors in anal carcinoma. Pathology 2002;34:573.
14. Tanum G, Tveit K, Karlsen KO, et al. Chemotherapy and radiation therapy for anal carcinoma: survival and late
morbidity. Cancer 1991;67:2462.
15. Bartelink H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to
radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the
European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative
Groups. J Clin Oncol 1997;15:2040
337
16. Gerard JP, Ayzac L, Hun D, et al. Treatment of anal canal carcinoma with high dose radiation therapy and
concomitant fluorouracil-cisplatinum. Long term results in 95 patients. Radiother Oncol 1998;46:249.
17. Constantinou EC, Daly W, Fung CY, et al. Time-dose considerations with treatment of anal cancer. Int J Radiat
Oncol Biol Phys 1997;39:651.
18. Hoffman R, Welton ML, Klenche B, et al. The significance of pretreatment CD4 count on the outcome and
treatment tolerance of HIV-positive patients with anal cancer. Int J Radiat Oncol Biol Phys 1999;44:127.
19. Place RJ, Gregorcyk SG, Huber PJ, et al. Outcome analysis of HIV-positive patients with anal squamous cell
carcinoma. Dis Colon Rectum 2001;44:506.
20. Cummings BJ, Brierley JD. Anal canal. In: Perez CA, Brady LW, Halperin EC, et al., eds. Principles and practice of
radiation oncology, 4th ed. Philadelphia: Lippincott, Williams and Wilkins 2003:1630.
21. Cummings BJ. Preservation of structure and function in epidermoid cancer of the anal canal. In: Rosenthal CJ,
Rotman M, eds. Infusion chemotherapy radiotherapy interactions: its biology and significance for organ salvage
and prevention of second primary neoplasms. Amsterdam: Elsevier Science Publishing Co, 1998:167.
22. Allal AS, Sprangers MA, Laurencet F, et al. Assessment of long-term quality of life in patients with anal
carcinomas treated by radiotherapy with or without chemotherapy. Br J Cancer 1999;80:1588.
23. Vordermark D, Sailer M, Flentje M, et al. Curative intent radiation therapy in anal carcinoma: quality of life and
sphincter function. Radiother Oncol 1999;52:239.
24. Tanum G, Tveit K, Karlsen KO, et al. Chemoradiotherapy of anal carcinoma: tumour response and acute toxicity.
Oncology 1993; 50:14.
25. Place RJ, Gregorcyk SG, Huber PJ, et al. Outcome analysis of HIV-positive patients with anal squamous cell
carcinoma. Dis Colon Rectum 2001;44:506.
26. Klencke BJ, Palefsky JM. Anal cancer: an HIV-associated cancer. Hematol Oncol Clin North Am 2003;17:859.
338
Sphincter Saving Surgeries for Rectal Cancers
Shukla PJ, Barreto SG, Shrikhande SV
A question often asked by a patient suffering from rectal cancer today is whether or not he / she will
be able to pass motions through the normal anal passage after surgery. This issue is more important
in the present times considering the widespread dissemination of information (I refrain from using the
word knowledge) on sphincter preserving surgeries as it may often lead to unrealistic expectations
from patients. Looking on the bright side, the surgeon need not shy away from his patients
questioning gaze any more considering that there is increasing amount of published literature in the
world today confirming not only the feasibility, but also the oncological completeness of sphincter
preserving surgeries for rectal cancers when they are performed for the correct indications.
By sphincter preservation we mean all surgeries for rectal cancers in which the normal anal sphincter
is not destroyed by surgery so as to allow the patient to retain the ability to pass motions, through the
normal anal passage, at his will.
The important advancements that have made sphincter preservation possible include neoadjuvant
therapies (chemo- and radio-therapy), surgical skills, instrumentation (esp. circular end-to-end
stapling devices), changes in the accepted distal margin length1, coupled with a better understanding
of rectal cancer biology and the anal sphincter mechanisms. A brief look at each of these individual
factors is in order.
a) Neoadjuvant Therapies2-7 – The introduction of chemoradiotherapy in the neo-adjuvant setting
has helped in sphincter preservation by reducing tumour size, decreased nodal metastasis,
downstaging the T stage and increasing radial clearance. It has been proposed that
neoadjuvant radiotherapy may also change the distance of the tumour from the anal verge, in
patients who respond. This may not happen in all patients. This has been shown to change
the decision of surgery from an APR to a sphincter preserving surgery.
b) Surgical skills – Training in specialized high-volume centres provides the necessary skills and
the finer technicalities (including use of instrumentation) desired to perform these surgeries8.
c) Instrumentation – Circular stapling devices have enhanced the ease of performing end-to-end
anastomosis close to the dentate line.
d) Distal margin length –While a 2cm margin is preferred distally, a 1 cm margin may be
acceptable in distal rectal cancers9,10 based on studies demonstrating the lack of submucosal
extension of rectal cancers > 1cm11.
e) Rectal cancer biology and the anal sphincter mechanisms – an appraisal of matters such as
the tendency for rectal cancers to spread cranially more than caudally (at least initially), the
less likelihood of involvement of perirectal nodes in T1 tumours, the importance of the
external anal sphincter in regulating control over defecation are some of the issues that have
promoted the practice of sphincter preserving surgeries.
Types of Surgeries
Sphincter preserving surgeries for rectal cancer
1) Anterior resections (AR) are performed for tumours in the upper to middle third of the rectum.
Such a procedure involves removal of the sigmoid colon and proximal rectum by TME with an
anastomosis in the pelvis below the peritoneal reflection.
2) Ultralow AR (ULAR) is performed for tumours between 2 and 5 cm from the anal verge.
Colonic J-shaped pouch or coloplasty can be incorporated in to the procedure of anterior
resection especially ULAR, coloanal anastomosis with the possibility of reducing early bowel
alteration associated with these procedures.
3) Intersphincteric resections (ISR) which involves a transanal division and resection of all or
part of the internal anal sphincter has been performed in patients with tumours ranging from
1.5-4.5cm from the anal verge with a 89% complete microscopic resection and a 2% risk of
local recurrence12.
4) Local resectional surgery
This includes: transanal excision, transcoccygeal, transsphincteric, and transanal endoscopic
microsurgery (TEM can be performed in case of tumours located up to the rectosigmoid)
339
Indications for sphincter preserving surgeries
Distance from the anal verge is the most important factor in selecting patients for sphincter preserving
surgeries. Sphincter preservation should be considered in all patients with tumours more than 2 cm
from the anal verge. The only absolute contraindications for attempting sphincter preservation in very
low rectal cancers are:
1) unfavourable histology – poorly differentiated carcinomas, signet ring cell morphology
2) Infiltration of the external anal sphincter or levator ani muscles,
3) Impaired preoperative anal sphincter function
Selection Criteria for transanal procedures includes13:
Morphologic tumour characteristics

a) Tumours located 8-10cm from anal verge (exception TEM)
b) Size < 3-4cm in diameter
c) Exophytic tumour morphology
Tumour Staging
a) Tumours limited to bowel wall (incidence of lymph node metastasis ranges from
6-12% for T1 tumours while it is 51-66% for T3 lesions)14, 15
Tumour Histology
a) Tumour grade – low
b) Lymphovascular invasion – absence
c) Lack of mucinous component
d) Absence of tumour budding (small clusters of undifferentiated cancer cells ahead of
the invasive front of the lesion) at the invasive edge of the tumour
e) Differentiation – well differentiated lesions only
Patient Criteria
a) Continent patient
b) Physically unfit to undergo major surgery
c) Unlikely to benefit from major surgery due to presence of metastatic disease at
presentation
Pertinent investigations prior to the surgery

1. Biopsy – to confirm malignancy and determine tumour differentiation
2. Colonoscopy – to confirm, or rule out, synchronous polyps and malignancies
3. MRI - When used with endorectal coils, MRI has a reported accuracy of 72-100% in the local
staging of rectal cancers [16-18].
4. Endoscopic Ultrasound - It is now considered to be standard of care for staging of rectal
cancers. Its uses include:
 Determining sphincter involvement prior to undertaking sphincter-preserving surgery
 Accurate determination of T and N stage so as to plan for preoperative
chemoradiotherapy.
Limitations to this investigative modality include operator dependence, as well as tumour and
patient-related limitations.
Results
When we view the impact of sphincter-preservation in low rectal cancers, the two prime end-points to
be seen include firstly, the oncological outcome, and secondly the functional outcome and quality of
life. The oncological outcome has been satisfactorily addressed by numerous studies1,19-21. As
regards the functional outcome and quality of life, while the quality of life is definitely improved by the
avoidance of a stoma, the anorectal function often may fall short of perfect. The sexual dysfunction
after sphincter preserving surgeries does not appear to be any more than following an APR so long as
the surgeon practices a good total mesorectal excision with autonomic nerve preservation. It is
important to understand that sexual function is determined by factors other than the surgery like
neoadjuvant/adjuvant therapies, comorbidities and medications. The most common complication
encountered is an anastomotic leak that arises due to a number of factors including impaired
vascularity, tension on the anastomosis due to inadequate mobilization of the proximal bowel loop,
incorrect firing of the stapler, improper haemostasis, etc. From this list it is clear that most of the
340
factors are related to the surgeon. Hence, if a technically sound anastomosis is performed, the
incidence of a leak is similar to any other anastomosis of the bowel.
Our personal experience

Since the end of 2002, we have been practicing sphincter preserving surgeries (Double-stapling
technique) for low rectal cancers with satisfactory outcomes22. Our anastomotic leak rates have been
considerably low and comparable to those reported in literature. We hope this will serve as an
impetus to more and more surgeons in the country to adopt sphincter-preserving techniques and
transfer this advantage to their patients. We have also been performing laparoscopic ARs with
satisfactory short-term outcomes. We believe that the current data is as yet young and as such this
procedure should be performed within the confines of clinical trials23.
References
1. Di Betta E, D‘Hoore A, Filez L, et al. Sphincter-saving rectum resection is the standard procedure for low rectal
cancer. Int J Colorectal Dis 2003; 18: 463-469.
2. Tytherleight MG, McC Mortensen NJ. Options for sphincter preservation in surgery for low rectal cancer. Br J
Surg 2003; 90: 922-933.
3. Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl
J Med 1997; 336: 980-987.
4. Kim DW, Lim SB, Kim DY, et al. Pre-operative chemoradiotherapy improves the sphincter preservation rate in
patients with rectal cancer located within 3cm of the anal verge. Eur J Surg Oncol 2006; 32: 162-167.
5. Crane CH, Skibber JM, Feig BW, et al. Response to preoperative chemoradiation increase the use of sphincter-
preserving surgery in patients with locally advanced low rectal carcinoma. Cancer 2003; 97: 517-523.
6. Sauer R, Becker H, Hohenberger W, Rodel C, et al. Preoperative versus postoperative chemoradiotherapy for
rectal cancer. N Engl J Med 2004; 35: 1731-1740.
7. Szynglarewicz B, Matkowski R, Kasprzak P, et al. Sphincter-preserving R0 total mesorectal excision with
resection of internal genitalia combined with pre- or postoperative chemoradiation for T rectal cancer in females.
World J Gastroenterol 2007; 28: 2339-2343.
8. Iversen LH, Harling H, Laurberg S, Wille-Jorgensen P, Danish Colorectal Cancer Group. Influence of caseload and
surgical speciality on outcome following surgery for colorectal cancer: a review of evidence. Part 2: long-term
outcome. Colorectal Dis 2007; 9: 38-46.
9. Andreola S, Leo E, Belli F, et al. Distal intramural spread in adenocarcinoma of the lower third of the rectum
treated with total rectal resection and coloanal anastomosis. Dis Colon Rectum 1997; 40: 25-29.
10. Vernava AM III, Moran M, Rothenberger DA, et al. A prospective evaluation of distal margins in carcinoma f the
rectum. Surg Gynecol Obstet 1992; 175: 333-336.
11. Karanjia ND, Schache DJ, North WR, Heald RJ. ‗Close shave‘ in anterior resection. Br J Surg 1990; 77: 510-512.
12. Rullier E, Laurent C, Bretagnol F, et al. Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm
distal rule. Ann Surg 2005; 241: 465-469.
13. Perretta S, Guerrero V, Garcia-Aguilar J. Surgical treatment of rectal cancer: Local Resection. Surg Oncol Clin N
Am 2006; 15: 67-93.
14. Sitzler PJ, Seow-Choen F, Ho YH, et al. Lymph node involvement and tumour depth in rectal cancers: an analysis
of 805 patients. Dis Colon Rectum 1997; 40-1472-1476.
15. Zenni GC, Abraham K, Harford FJ, et al. Characteristics of rectal carcinomas that predict the presence of lymph
node metastases: implications for patient selection for local therapy. J Surg Oncol 1998; 67: 99-103.
16. Murano A, Sasaki F, Kido C, et al. Endoscopic MRI using 3D-spoiled GRASS (SPGR) sequences for local staging
of rectal carcinoma. J Comput Assisst Tomogr 1995; 19: 586.
17. Joosten FBM, Jansen JBMJ, Joosten HJM, et al. Staging of rectal carcinoma using MR double surface coil, MR
endorectal coil, and intrarectal ultrasound: Correlation with histopathologic findings. J Comput Assisst Tomogr
1995; 19: 52.
18. Blomqvist L, Machado M, Rubio C, et al. Rectal tumour staging: MR imaging using pelvic phased-array and
endorectal coil vs endoscopic ultrasonography. Eur Radiol 2000; 10: 653-660.
19. Guillem JG. Ultra-low anterior resection and coloanal pouch reconstruction for carcinoma of the distal rectum.
World J Surg 1997; 21: 721-727.
20. Jeong SY, Chessin DB, Guillem JG. Surgical treatment of Rectal Cancer: Radical Resection. Surg Oncol Clin N
Am 2006; 15: 95-107.
21. Nakagoe T, Ishikawa H, Sawai T, Tsuji T, Tanaka K, Hidaka S, et al. Survival and recurrence after a sphincter-
saving resection and abdominoperineal resection for adenocarcinoma of the rectum at or below the peritoneal
reflection: a multivariate analysis. Surg Today 2004; 34: 32-39.
22. Shrikhande SV, Saoji RR, Barreto SG, Kakade AC, Waterford SD, Ahire SB, Goliwale FM, Shukla PJ. Outcomes of
resection for rectal cancer in India: The impact of the double stapling technique. World J Surg Oncol 2007; 5: 35.
23. Shukla PJ, Barreto G, Gupta P, Shrikhande SV. Laparoscopic surgery for colorectal cancers: Current Status. J
Min Access Surg 2006; 2: 205-210.
341
Adjuvant therapy in Rectal Cancer
Dr P. K. Julka
Introduction
Colorectal cancers figure among the 10 commonest cancers in Indian population, the reported age-
standardized incidence and mortality rates per 100,000 being 4.7 and 3.4 in males, and 3.2 and 2.2 in
females respectively (GLOBOCAN 2002, IARC). These numbers translate into annual incidence of
19,508 in males and 13,555 in females, with a third of these numbers being contributed by rectal
cancer.
Surgery is the cornerstone of therapy in rectal cancer. The introduction of total mesorectal excision
has reduced local recurrence rates from 39% to 10%.1 However, surgery alone has a reported
locoregional recurrence of 25-50%, thus adjuvant radiotherapy (RT) and chemotherapy are
administered to improve local tumor control, decrease morbidity, and prolong survival.2 Several
prognostic factors including stage, extent of resection, molecular markers (p53 status, S phase
fraction, aneuploidy, Ki67) and tumor characteristics (distal location, fixed tumor, circumferential
lesion, near obstructing lesion) may help identify patients at high risk of recurrence, who may benefit
most from adjuvant therapy.3
The sequencing of RT and chemotherapy with surgery is an issue of constant debate. The last three
decades have witnessed constant evolution in treatment strategies in preoperative and postoperative
setting, and introduction of several new chemotherapeutic agents and molecular targeted therapy.
Radiotherapy
Postoperative radiotherapy
Postoperative RT (PORT) has the inherent advantage of availability of accurate staging information
from postoperative histopathology, consequent to which only tumors with unfavorable prognostic
factors are treated, while the demerits include irradiation of larger volumes, small bowel irradiation,
low efficacy in the setting of hypoxia and poor tolerance to treatment. Several randomized trials have
shown superiority of PORT at doses of 40-50 gray added to surgery with a local control of 80-85%
and a disease free survival of 50-65%. However, conventional fractionation schedules have failed to
demonstrate a survival benefit.4-6 Further studies demonstrated even better outcomes with addition of
chemotherapy to postoperative RT. Two of these, including those by GITSG 7175 and Mayo/NCCTG
79-47-51 have shown improvement in local control as well as disease-free and overall survival.7-10
(Table 1)
An NIH consensus development conference recommended that all patients with stage II or III rectal
cancer should receive postoperative combined modality treatment.11 Another such recommendation
was given supporting postoperative combined modality treatment for stage 2 and 3 carcinoma rectum
by the German Cancer Society Consensus Conference.12
Preoperative radiotherapy
Several European trials have focused on the use of preoperative or neoadjuvant RT. It has the
potential to downstage the locoregional disease and sterilize tumor margins thus improving
resectability for borderline operable disease as well as increasing sphincter preservation rates for low
lying tumors. RT is more effective in the presence of intact oxygenation of tissues, and downstaging
may serve as a surrogate for clinical efficacy. Lesser small bowel volume is irradiated, irradiated large
bowel is excised while the anastomosis is not irradiated. However, accurate pathological stage
remains unknown resulting in overtreatment of a proportion of early stage disease while definitive
surgery is delayed. Concerns have also been expressed regarding the detrimental impact on
postoperative wound healing.
Low dose preoperative RT (≤20 gray) has been ineffective in improving local control, disease-free or
overall survival.13 Both conventional schedules delivering doses of 40-45 gray over 4-5 weeks and
short course schedules delivering high dose per fraction are effective. Schedules delivering 50 gray
342
with conventional fractionation of 1.8-2 gray per fraction have a high therapeutic ratio but delay
surgery by over 4 weeks consequent to the radiation-induced edema. Swedish investigators have
used doses of 5 gray (Stockholm I) or 5.1 gray (Stockholm II or Swedish Rectal Cancer Trial) per
fraction delivered over 5 days.14,15 These are as effective as conventional schedules, are cost-
effective, safe and have become immensely popular. The Stockholm II trial also showed for the first
time an improvement in overall survival (58% vs 48% at 5 years) compared with surgery alone. The
risk of late toxicity due to the high dose per fraction has been anticipated but never confirmed in the
trials. An update of the Swedish Rectal Cancer Trial confirmed the benefit in overall survival and local
control at a follow up of 13 years but also demonstrated an increase in the risk of second
malignancies (RR 1.85) with short course RT.16 Surgery is carried out in a week‘s time after
completion of short course RT, however, it is ineffective in downsizing the tumor. (Table 2) Short
course RT is beneficial even when added to total mesorectal excision, emphasizing the fact that
improved surgical techniques are not a substitute to adjuvant RT.17
Preoperative RT in combination with chemotherapy has significantly improved sphincter preservation

rates, improved complete responses as well as disease-free and overall survival.18-20 However, there
have been no trials combining chemotherapy with short-course RT. (Table 3)
The benefit with adjuvant RT with respect to local control, disease-free and overall survival both in the
preoperative and postoperative setting has been demonstrated by a couple of meta-analyses. Table 4
shows the salient features of these studies.21,22
Postoperative vs preoperative radiotherapy
The Uppsala trial compared preoperative RT (25.5 gray in 5 fractions) to postoperative

chemoradiation (60 gray over 8 weeks) and showed the superiority of preoperative arm in terms of
lower local recurrence ((12% vs 21%; p=0.02) and better tolerability with equivalent overall survival
and metastases-free survival.23 A randomized phase III trial from the German Rectal Cancer Study
Group showed that preoperative 5FU-based chemoradiation over 5 weeks is achieves higher local
control and sphincter preservation than similar treatment given postoperatively. The incidence of
acute and long-term toxicity, mainly gastrointestinal also favors preoperative treatment.24 Two other
trials (NSABP R-03 and RTOG) had similar objectives but were closed prematurely due to low
accrual.
Therefore, preoperative chemoradiation with its better tolerability and improved local control may be
considered as the new standard treatment of rectal cancer although no differences in distant
metastases or overall survival exists.
Table 1. Randomised trials with PORT with/ without chemotherapy in carcinoma rectum
Year Dose Chemo Local DFS (%)

failure
(%)
Postop RT
Danish Cancer 50 Gy/25# 16 65
1 1986
Society - 18 69
50 Gy/25# 24 55
2 Netherlands 1991
- 33 60
40 Gy/20# 21 47
3 MRC 1996
- 34 31
Postop CT+RT
4 GITSG 7175 1985 40-48 Gy/ - 20 52
20-25#
- 5FU/methyl 27 54
CCNU
40-48 Gy/ 5FU/methyl 11 67
20-25# CCNU
- - 24 45
5 Mayo/NCCTG 1991 40-50 Gy/ - 25 38
343
79-47-51 25-28#
40-50 Gy/ 5FU/methyl 13.5 58
25-28# CCNU
6 NSABP R-01 1988 46-47 Gy/ - 16 35
26/27# - 25 29
- 5FU/methyl 21 42
- CCNU/VCR
7 Norwegian 1997 46 Gy/23# 5FU 12 64
Radium Hospital
- - 30 46
Table 2. Trials comparing short course preoperative RT with surgery alone in rectal cancer
DFS
Year Dose Local failure (%)
(%)
EORTC 1988 34.5 Gy/15# 14 68
- 28 59
Stockholm I 1995 25.5 Gy/5# 11 72
- 25 52
Stockholm II (SRCT) 1997 25 Gy/5# 11 74
- - 27 65
MRC 1996 40 Gy/20# 36 28
46 7
Stockhom II (update) 2005 25.5 Gy/5# 9 72
- 26 62
Table 3. Trials showing results with combined preoperative chemoradiation in rectal cancer
Local Sph. Comments

Dose Chemo recurrence Preservation Survival
(%) (%)
45 Gy + ↑ resectability
Chao 5FU+/-
5.4-14.4 7.2 (at 2y) 64 2y OS-90.5% ↓ postop morbidity
2005 LV Downstaging in 68%
Gy
Survival assoc with
 Path resp ≥95%
10y OS- 58%  LVI
Guillem
50.4 Gy 5FU/Iri - 71 10y DFS-
2005
62%
 Perineural inv.
 LN+
Downstaging in 58%
Med OS- Duke‘s stage assoc with
Kurt 30.73 m mets
50.4 Gy 5FU - -
2005 Med DFS-
39.4 m
344
Table 4. Adjuvant RT- meta-analyses
Study RT setting Findings

Colorectal Cancer Postoperative 8 trials; 2157 patients
Collaborative Group Significant ↓ in risk of 5 year local recurrence in
PORT gp (15% vs 23%)
No significant change in 5 year mortality rate in
PORT gp (58% vs 59%)
Preoperative 14 trials, 6350 patients
Significant ↓ in positive LNs at resection (32% vs
38%)
Significant ↓ in local recurrence (13% vs 22%)
Significant ↓ in absolute risk of recurrence at 5y
(46% vs 53%)
No change in OS at 5 years
Camma et al Preoperative Significant ↓ local recurrence (OR 0.49)
Significant ↑ 5 yr OS (OR 0.84)
Significant ↓ cancer-related mortality (OR, 0.71)
No ↓ in distant mets
Significant ↑ sepsis (21% vs. 15%) and other
complications (21% vs. 18%)
Preop RT was found to be more detrimental in
patients receiving > 3000 cGy
Adjuvant chemotherapy
Concomitant to radiation
Chemotherapy concurrent with RT is used for its radiosensitizing properties to improve resectability
and sphincter preservation in preoperative setting and reducing local failure rates. Chemotherapy has
been delivered both concurrently and sequential to irradiation in most trials, thus a direct cytotoxic
effect over the observed gain in local control cannot be excluded. The benefits of adding
chemotherapy to either regimen has been demonstrated earlier (Tables 1& 3), and the issues
precluding combining it with short course irradiation due to the large dose per fraction of RT has also
been discussed. Addition of chemotherapy inevitably increases the toxicity related to treatment, but
most side effects are predicable and manageable allowing >80% compliance without impairing the
delivery of full RT doses.25
Sequential to radiation
Sequential chemotherapy following concomitant chemoradiation is generally delivered for a total of 6

monthly cycles, aimed at complementing the reduction of local failures achieved through
radiosensitization with a reduction in distant failures and improvement in survival. A pooled analysis of
5 randomized studies showed a 20% absolute survival benefit with postoperative chemotherapy
administered for 6-12 months compared with observation or PORT alone.26 No randomized studies
have confirmed this benefit of adjuvant chemotherapy directly, therefore this issue remains debatable.
Whether adjuvant chemotherapy can be omitted in patients with a good response to preoperative
chemoradiation is another controversial issue notwithstanding the excellent long term prognosis in
these cases; however the contribution of chemotherapy cannot be excluded since even these patients
received adjuvant chemotherapy regardless of response. Retrospective analyses appear to show that
patients responding well to preoperative chemoradiation are also those achieving greater benefit from
adjuvant chemotherapy.27
Chemotherapy regimens
The standard schedule of concurrent chemotherapy includes continuous 5FU infusions. A

retrospective pooled analysis of phase II-III trials including 3157 patients showed greater pathological
complete responses with infusion regimens given preoperatively.28 Protracted infusion regimens all
through RT or for at least 5 days during the first and last week of RT, are most popular. Postoperative
data are less clear about the benefit of infusional regimens over bolus 5FU, and in such settings, the
common practice as well as control arms of clinical trials use either of the two schedules with or
345
without leucovorin. Several new drugs under investigation for colon cancer have radiosensitizing
properties as well and have potential for use in rectal cancer treatment for improving efficacy,
reducing distant failures and better tolerance or patient convenience. These include irinotecan,
oxaliplatin, capecitabine, cetuximab and bevacizumab.
Oral fluoropyrimidines such as capecitabine and uracil/tegafur (UFT) mimic the infusional plasma
levels of 5FU. Capecitabine at doses of 825 mg/m2 twice daily given throughout the week for the
duration of standard RT (50.4 Gy at 1.8 Gy per fraction) is recommended on the basis of phase I
studies. Toxicity is manageable, with grade 3-4 diarrhea occurring in 4-13% patients, other toxicities
being radiation dermatitis (2-6%), hand-foot syndrome (2-11%) and neutropenia (4-10%) An ongoing
study, NSABP R-04, is evaluating the role of capecitabine as a substitute to 5FU infusion either as
single agent or in combination with oxaliplatin concurrent with preoperative RT. Table 5 list the studies
testing newer preoperative chemoradiation regimens for either replacement of 5FU or combination
with other active agents such as oxaliplatin. The ongoing PETACC 6 study is evaluating the role of
capecitabine-based preoperative chemoradiation followed by postoperative capecitabine in
comparison to a capecitabine-oxaliplatin combination given concurrent with preoperative RT and
postoperatively.
Table 5. Newer preoperative chemotherapy and biologic therapy regimes

Aim Regimen pCR (%) Gr 3-4 toxicity (%)
Simplification Capecitabine 4-31 6-40
UFT 8-25 6-32
Eniluracil 6 -
Potentiation 5FU + Oxaliplatin 7-36 6-39
Capecitabine/UFT + Oxaliplatin 6-29 6-33
Raltitrexed + Oxaliplatin 14 7-23
5FU + Irinotecan 14-26 2-32
Capecitabine/UFT + Irinotecan 9-33 8-66
5FU/Capecitabine + Oxaliplatin/Irinotecan + 5-25 8-27
Cetixumab
Capecitabine + Geftinib - 33
5FU + Bevacizumab - 0
Biologic agents
Incorporation of biologically targeted agents may further improve outcomes in rectal cancer, with use
of radiosensitizing agents as with EGFR inhibitors (both tyrosine kinase inhibitors and monoclonal
antobodies) in combination with preoperative RT, and anti-angiogenesis agents such as
bevacizumab, the role of which has been established in metastatic and to some extent, advanced
colon cancer, and is now being extended to rectal cancers as well.
Conclusions
Adjuvant therapy is an integral component of stage II-III rectal cancer, with either preoperative or
postoperative regimens combining RT with chemotherapy proving better than surgery alone. Short
course preoperative RT is as effective as longer schedules and is attractive in terms of cost-
effectiveness and convenience, however the long term morbidity and risk of second malignancies
need to be addressed. Introduction of newer chemotherapeutic and biologic agents has increased the
options for improving treatment results with lower toxicity. Improvement in diagnostic tools such as
MRI and development of biologic markers and pharmacogenomics may help determine the stage and
prognosis of disease at diagnosis, and in better identifying responders and non-responders early, thus
allowing development of individually tailored treatment programs and optimizing the use of available
treatment regimens.
346
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347
Management of Recurrent Rectal Cancer
Dr. Amar Bhatnagar,Dr. Arvind Kumar Mishra
More then 50% patients will develop tumor recurrence after curative surgery. Likelihood of developing
recurrence depends upon stage, distance from anal verge, grade, aneuploidy, surgical techniques
employed and use of adjuvant therapy. Eighty five percent recurrences occur in the first 2.5 years;
15% after 2.5 years. After 5 years ,5% patients develop recurrence. Out of all recurrences, in 50-80%
patient‘s local recurrence is the only site. Local recurrence rates of between 3-32% have been
reported, higher rate if surgery is sub optimal. In first two years post operatively most local recurrence
appear. It is important to note that clinical nature and prognosis of patients with locally recurrent rectal
cancer has changed since the introduction of preoperative radiotherapy. Adjuvant radiotherapy will
delay local recurrence and 50% will occur after 2 years. Recurrence rate is also decreased with
preoperative radiotherapy. Majority of patients who present with local recurrence after preoperative
radiotherapy have simultaneous distant metastasis and median survival has decreased to six
months.
Prevention of local recurrence by proper selection of primary cases, the training of surgeons, use of
total mesorectal excision and optimal use of adjuvant therapies (Radiotherapy and Chemotherapy) is
the way forward to improve treatment results.
Pelvic recurrence can be central, pelvic sidewalls and sacral. Central recurrence is commonest and
has best prognosis. Sacrum is the least common site of recurrence. Pelvic side wall recurrence has
least favorable prognosis.
Tumor invasion of the bladder base, sacral nerve roots and pelvic floor produces distressing
symptoms. Severe pain, bleeding, bowel and urinary obstruction, fecal and urinary leakage are other
symptoms. Without surgical intervention, 5 years survival rate is less than 4%.
Diagnosis:
Diagnosis of local recurrence is made at a late stage because of the high rate of asymptomatic
patients, 56% in the experience of Mayo clinic. Diagnosis is complicated by radiation and
postoperative changes that are often difficult to distinguish from tumor.
Good history with details of previous treatment, clinical examination, blood counts, chest x-ray and
proctoscopy is done. Rectal examination is still the best tool to detect early anastamotic recurrence.
Colonoscopy will rule out disease in other parts of colon.
Carcinoembryogenic antigen (CEA) is most useful in patients in whom levels are increased
preoperatively and returns to normal after surgery. After surgery first CEA estimation is done after six
weeks. Preoperative CEA that does not normalize postoperatively suggest incomplete resection,
recurrence or false positive.
Elevated CEA after normalization suggest recurrence. Rapid elevation suggests liver or lung
involvement. Slow gradual rise is associated with loco regional recurrence. In hepatic recurrence CEA
is elevated in 80-90% of patients. In loco regional recurrence 20-30% patients do not have raised
CEA. Poorly differentiated tumors do not make CEA. Median lead time of elevated CEA to detection
of recurrence by other means is six months. Seven percent patients with elevated CEA failed to have
identifiable recurrence.
Endorectal ultrasonogram (ERUS) is highly operator dependent and is superior to CT to assess local
disease.
CT of chest, abdomen and pelvis is performed to exclude distant metastasis and adjacent organ
involvement. MRI may yield added information on resectability. Sensitivity of MRI is 77-100% but
specificity is low 29-86% leading to false positive diagnosis. If a mass displays rounded margins,
recurrence is likely whereas straight angular margins are more typically found with fibrosis. Lymph
node staging accuracy in ERUS is 62-83%, CT 35-73% and MRI 39-84%. 50-75% positive lymph
348
nodes are normal in size. Lymph node greater than 3mm and hypoechoic are likely to contain
metastasis.
Urinary tract evaluation by IVP, CT scan or Cystoscopy is advisable.

PET reports increased accuracy in distinguishing postoperative changes from recurrent tumor – 95 %
sensitive, 98 % specific. PET/CT is superior to PET alone. Contrast enhanced Endorectal MRI is very
promising in staging and differentiating between scar tissue and recurrent cancer.
PET is useful in rising CEA with normal x-rays. CT and MRI are not sensitive enough to identify low
volume disease. PET is more sensitive. It alters management in 37 % of patients with recurrent
colorectal cancer. It has greatest impact by detecting un-resectable disease.
Immunoscintigraphy with (99m) Tc labeled anti CEA monoclonal Ab (MoAb) CL-58 has high specific
and predictive value for detecting local recurrence. Indium- 111- labeled mAb to B 72.3 that targets
tumor associated glycoprotein TAG- 72 is reactive in 83% colorectal cancer. These studies are
especially useful for case with raised CEA but no radiological abnormality and to rule out metastatic
disease in patients with loco regional disease.
FNAC maybe unsuccessful due to scanty cellular population found with recurrent tumor masses.
Multiple core biopsies are often required for histo-pathological diagnosis.
Treatment:
Goal of treatment is to provide symptomatic relief and prolong survival and/or achieve cure.
Resectable recurrence: Aim of surgery is Ro resection by doing enbloc resection of tumor and
adjacent involved structures. Non critical tissues including hypogastric vessels, lymph nodes, bladder,
vagina, prostate, part of sacrum can be scarificed to achieve negative margin. Palliative resection of
macroscopic residues is not recommended. Contraindication for curative surgery are :
1. Tumor involvement of S1/S2 nerve roots.

2. Proximal sacral invasion above the level of S2/S3 Junction as this precludes partial
sacrectomy.
3. Extensive pelvic side wall involvement.
4. Tumor encasement of iliac vessels.
5. Extension of tumor through the greater sciatic notch.
Surgical management of locally recurrent cancer may involve major procedure and is not for the faint
hearted. Ro resectability rate are 30% to 45%.
As long as the pelvic floor is not directly affected by the recurrent tumor or by extent of surgical
resection, restoration of bowel and urinary tract continuity are technically feasible.
It is justified to do abdominoperineal resection for a local recurrence after low anterior resection
whenever possible. Advanced techniques of ultralow sphincter saving resection of rectum and
coloanal anastamosis and bladder sparing or partial cystectomy or reconstruction of an neo bladder
can be used. Rectal continent preservation is attempted only if anal sphincter complex – puborectalis
,pubococygeus or leavator ani muscles are free of recurrence. Presence of hydronephrosis correlates
with larger recurrent tumors undergoing more extensive operations and multimodality therapy but
does not preclude curative (Ro) resection.
Composite sacropelvic resection is a high risk procedure that benefits selected patients.
Sacral resection can be performed below S2 and S3 level. Sacrectomy is indicated either because of
tumor adherence or cortical invasion. Pelvic sepsis and perineal wound breakdown are major
complications. Use of rectus or omental flaps to fill the pelvic cavity reduce wound breakdown.
In selected patients Ro resection may require pelvic exenteration. Anterior pelvic exenteration implies
removal of bladder,distal ureters, internal genital organs, lymph nodes. Posterior pelvic exenteration
349
implies removal of rectum, distal colon, internal genital organs and lymph nodes. Pelvic exenteration
may or may not include sacrectomy.
Adjuvant therapy to surgical resection:
Management of locally recurrent rectal cancer is always multimodality treatment including

preoperative radiotherapy, chemotherapy and Intraoperative radiotherapy by either electron beam
irradiation or with high dose brachytherapy. Combination of a chemotherapy as a radio sensitizer
results in an increase of Ro resection by 20%. One of the schedule is preoperative radiotherapy 45
Gy in 25 fractions with boost to tumor bed to total dose of 50.4 Gy in 28 fractions along with either
continuous 5 FU infusion 300mg/m2/day 5 days a week or Capecitabine 850 mg/m2/day 5 days a
week with surgery 6-8 week later and use of intra operative radiotherapy boost in patients with
positive margin or close margin.
Advantages of intra operative radiotherapy (IORT) are:
1. Increases local control in high-risk cases.

2. Accurate treatment of focal areas at risk.
3. Ability to adjust the depth of the radiation beam.
4. Ability to shield sensitive structures.
Intra operative radiotherapy dose ranges from 10-20 Gy. 10-13 Gy for close margins (<5mm), 15 Gy
for microscopically positive margins, and 17 to 20 Gy the areas of gross residual disease.
Intraoperative brachytherapy allows radiation access in areas where the IORT beam cannot be
focused due to anatomical constraints of pelvis. 10-20 Gy is used selectively.
Radiation therapy (Intraoperative Electron Beam Therapy and External Beam Radiation Therapy) can
be a component of aggressive multimodality treatment in patients with recurrent cancer who have
received previous External Beam Radiation Therapy.
Prognostic factors:
Initial surgery with endcolostomy, symptomatic pain and increasing number of sites of recurrent tumor
fixation in the pelvis is more often associated with palliative surgery. Most important prognostic
variable is the state of surgical resection margin that is Ro resection.
In composite sacropelvic resection - less blood transfusion, Ro resection, lack of anterior organ
involvement and absence of cortical bone invasion associated with better prognosis.
Preoperative CEA, preoperative CEA doubling time, performance status and use of preoperative
radiotherapy can help patient selection before surgery. Non- demolitive surgery at first excision allows
for easier curative second surgery. APR makes early detection of recurrence difficult. Female gender
is associated with better outcome probably due to wide pelvis which makes execution of extensive
operations feasible.
Absence of vascular invasion is an independent predictor of local control and improved survival.
Results:
Approximately two third of patients with locally recurrent rectal cancer can be resected for cure.
Despite surgery and IORT, local failure rate is high.
Memorial Sloan Kettering Cancer Center,New York reports 2 years recurrence rate of 33% and 73%
in patients with negative and positive margin and 5 year survival rate of 51% and 16% respectively.
Most favorable outcome in true anastomatic recurrence is 78% five year survival. Mariya, Y., from
Japan reports 5 year survival up to 31% and local control rate of 50-71% after Ro resection. Palmer
G., et.al Sweden reports 5 years survival of 57% after Ro resection. 5 years global survival is between
30-40%.
350
After composite sacropelvic resection, MS KCC, New York reports 2 years and 5 years recurrence
rate of 47% and 85% .After total pelvic exenteration with negative CEA and Ro resection – 3 and 5
years survival rates are 62% and 42%.
MD Anderson cancer center reports 77% resection rates, 88% Ro resection, 64% local control rate
and 58% 5 years survival.
After enbloc resection of tumor fixed to urinary tract, Stocchi, L., et al reports 1,3 and 5 years survival
rates of 82%, 45% and 19% with median survival 2.6 years.
After total pelvic exentration 5 years survival ranges from 0-32%, 3 years survival 32%.
As a result of multimodality treatment the majority of these patients have to deal with long term
physical morbidity, the need for help with daily care and considerable social impairment. These
consequences must be weighted against the chances of cure if patient is treated and the disability
eventually caused by uncontrolled tumor progression if the patient is not treated. This should be
discussed with the patient when designing a treatment strategy. Long term survivors (> 3 years)
report very good quality of life.
Irresctable locally recurrent rectal cancer:
When left untreated results in a median survival of 7-8 months. EBRT alone provides short term
palliation in 70% patients. 5 years survival after EBRT is achieved in only 2-5% patients.
High dose rate intraluminal brachytherapy can be used in patients with recurrent rectal cancer in
patients who has received surgery and EBRT. Large bowel obstruction can be palliated using self
expendable endoprosthesis. Better to avoid palliative colostomy if possible. In unresectable pelvic
recurrence radiofrequency thermal ablation is viable option for controlling pain and improves quality of
life.
Liver metastasis:
Symptomatic hepatic metastasis is a late occurrence. They are routinely detected during
postoperative follow up imaging and CEA estimation. Systemic chemotherapy can reduce volume of
tumor and facilitate surgery. 13% of unresectable liver metastasis becomes resectable after
chemotherapy. Multiple metastases that continue growing during chemotherapy should be out of
resection. High tumor volume, large tumor size and extensive resections are no longer barriers to
resection. In cases of bilateral disease multistage approaches to surgery can be considered.
Future liver remnant (FLR) defines resectibility.When all hepatic disease can be excised with negative
margin,leaving an adequate FLR, 20% of the standardized Total Liver Volume(TLV) with adequate
vascular inflow, hepatic venous out flow and billary drainage, metastasis should be deemed
resectable.
TLV(cm3) = -794.41 + 1267.28 X BSA (sq.mtr)
Standardized FLR = measured FLR Volume/ TLV
During resection 1 cm. margin remains the goal but close margin negative resection is also safe.
Anatomic oriented resection is favored over wedge resection because it is associated with less blood
loss and less likelihood of positive margin. There is no oncologic indication for which anatomical
resection is preferred to wedge resection.
Gold standard 5 years survival rate is 53-58%.
Radiofrequency ablation is inferior to resection in terms of both overall and diseases free survival.
Hepatic arterial infusion for unresectable diseases has failed to keep pace with improving
chemotherapy.
351
Lung metastasis:
Pulmonary metastasis occurs in 10-20% patients with colorectal cancer. Usually associate
with hepatic metastasis and extensive metastatic diseases.
Distal rectal lesions venous drainage by passes portal system and can produce isolated
pulmonary metastasis. Solitary pulmonary lesion in chest should be investigated to rule out
primary lung tumor or metastasis.
Treatment is minimal procedure to obtain negative margin (wedge resection). Patients with
solitary metastsis experience the best survival. But as many as three lesion can experience
40% 5 years survival.
Survival is correlateds with number of metastasis.
Recurrence in the lung after resection is an indication for repeat resection.
Patients who undergo repeat thoractomy do not fare worse than those who have single
pulmonary intervention.
Ovarian metastasis:
When isolated metastatic disease to one ovary is identified, a bilateral oopherectomy is
performed because there is high risk for bilateral involvement.
Brain metastasis:
It is uncommon and usually occurs after established lung involvement. Solitary lesion treated
by palliative craniotomy, resection and postoperative radiotherapy.
Bone metastasis:
It is uncommon and managed with radiation therapy.
Unresectable metastatic disease: Median survival without systemic chemotherapy ranges 6-9
months. 5-FU and leucovorin provides 12% to 40% response rate (RR) and median survival 10-17
months. Irinotecan and Oxaliplatin are new drugs. Various combinations – 5 FU+LV+ Oxaliplatin,
FOLFOX(5 FU, folinic acid, oxaliplatin) and FORFIRI( 5FU +, folinic acid + Irinotecan) yield greater
than 50% response and median survival greater than 20 months. New biological agents that targets
angiogenesis increases response rate from standard chemotherapy by about 10%.
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353
Surgical Management of Ulcerative Colitis
Dr. VK Kapoor
Introduction
Ulcerative colitis (UC) is a mucosal inflammatory disease of the large bowel which usually affects the
young. It starts in the rectum and involves the colon in contiguous fashion (cf. Crohn‘s disease –
patchy involvement). It is confined to the large bowel only and does not involve the small bowel (cf.
Crohn‘s disease which can involve any part of the GI tract). The disease is characterized by a course
of relapses and remissions.
Medical Management
The mainstay of management of UC is with drugs – amino-salicylates (ASA). Drugs, however, are
palliative only, have to be taken life-long, may have side effects and are expensive. Steroids should
be used for inducing a remission only and not for maintenance of a remission. Immunosuppressants
e.g. azathioprine, 6 mercapto-purine (6-MP) may be used for steroid dependant (acute attack
responds to steroids but relapses after steroids are withdrawn) and steroid resistant (acute attack
does not respond to steroids) cases – their long-term use is, however, associated with an increased
risk of cancers, especially lymphoma. Such patients may need surgery.
Emergency Surgery
A severe (fulminant) attack of acute UC can occur in about 15% of patients. Such an attack not
responding to intensive regimen with intravenous steroids for 3-7 days is an indication for semi-
emergency surgery. This can be further complicated by bleeding, toxic mega colon and perforation –
all indications for emergency surgery. Most of the times this surgery would be in the form of total
colectomy, terminal ileostomy and rectal stump (closed or brought out as a mucous fistula). Rectal
stump should not be closed if the patient has poor nutritional status or is on long-term steroids or the
rectal wall is severely inflamed and friable – risk of suture line giving way (blow out) is very high in
such cases. Mucous fistula is a safer option – the only disadvantage being a longer diseased rectal
remnant (which can be treated with local ASAs or steroids). Emergency surgery for UC may carry a
mortality of 5-15%.
UC and Cancer
Patients with UC die not of the disease but of cancer, complications of disease and complications of
management (drugs and surgery). Cancer is a definite complication of UC. Risk of cancer depends
upon age of onset of disease, duration of disease and extent of disease. Colo-rectal cancer in a first-
degree relative, endoscopic/ radiological stricture and primary sclerosing cholangitis also increase the
risk of cancer in UC. The cumulative risk of cancer is about 1% for every one year of the disease.
Cancer in UC can occur anywhere in colon, is more often multi-focal and usually undifferentiated.
Early age of onset, long duration of symptoms and pancolitis carry a very high risk of cancer and may
indicate elective (prophylactic) surgery. Patients with UC should be on surveillance for cancer with full
colonoscopy and multiple biopsies every 1-2 years. Presence of dysplasia on biopsy is also an
indication for prophylactic surgery.
Elective surgery
UC in children and adolescents may result in malnutrition and adversely affect growth and
development. Recurrent frequent acute attacks interfering with quality of life and causing chronic ill
health may indicate elective surgery. Severe debilitating extra-colonic manifestations of the disease
may also indicate elective surgery as some of them subside after the diseased colon is removed.
About 30-40% of patients with UC may require surgery at some stage of the disease. Surgery is the
only curative option for UC. Elective surgery should be associated with almost no mortality. The option
of elective surgery should be thought of, considered and offered to a patient with UC before it
becomes an emergency.
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Preparation
Nutritional status (anaemia, hypoalbuminaemia and electrolyte imbalance) should be corrected before
elective/ semi-emergency surgery. Sphincter (resting tone and squeeze pressure) should be
evaluated (before a restorative surgical procedure is planned). RPC/ IPAA should not be performed in
patients with lax sphincter as they will be completely incontinent. Patient should be counseled and
prepared for an ileostomy (temporary or permanent). Male patients should be cautioned about
impotence (retrograde ejaculation) and females for low fertility after surgery.
Surgical Procedures
The conventional surgical procedure for UC was pan-procto-colectomy (PPC) with permanent
terminal ileostomy. While it is curative (removes all diseased mucosa) it is ablative (sacrifices the
sphincter). Since the disease is mucosal (not full thickness cf. Crohn‘s disease) it is not necessary to
sacrifice the sphincter which can be preserved while the diseased rectal mucosa is removed.
Dissection in UC is peri-muscular (cf. mesorectal in cancer) – this avoids damage to pelvic nerves and
reduces the genitor-urinary complications of rectal excision. The terminal ileum can then be joined to
the anal canal. Usually an ileal pouch is created and an ileal pouch anal anastomosis (IPAA) is
performed – this is called restorative procto-colectomy (RPC). This can be hand sewn – a rectal
mucosectomy is performed preserving a 2-3 cm rectal muscular cuff. The ileal pouch comes through
this cuff and the IPAA anastomosis is performed manually per-anally at the dentate line. In a stapled
anastomosis, rectum is divided 1-2 cm above the dentate line and an end-to-end stapler is used for
IPAA (no rectal mucosectomy, no rectal muscular cuff, the rectum above the dentate line forms the
lower doughnut). Ileal pouch can be made hand sewn or with staplers. Pouch can be 2-loop (J), 3-
loop (S) or 4-loop (W) – each loop of 15 cm. RPC can be performed laparoscopically with the use of
Endo GIA for making the pouch and EEA staplers for IPAA.
Surgery can be single-stage – RPC/ IPAA with no covering ileostomy – elective operation in a young,
fit patient with good nutritional status who is not on steroids – an infrequent situation. It is usually two-
stage – RPC/ IPAA with covering ileostomy in first stage followed by ileostomy closure in second
stage. When performed for an emergency indication in a patient with poor nutritional status and on
steroids, it has to be three-stage – total colectomy with ileostomy and rectal stump in first stage, RPC/
IPAA with retention of covering ileostomy in second stage followed by ileostomy closure in third stage.
Complications of Surgery
Pouch/ anastomosis leak and pelvic sepsis are the commonest complications of RPC/IPAA. Pelvic
sepsis adversely affects the function of the pouch and increases genito-urinary neural damage.
Pouchitis is a long-term complication of pouch occurring at some time or the other in 30-50% of
patients. It is chararcterised by frequent discharge of mucous, pus and blood with fever and
leucocytosis. Pouchoscopy reveals active inflammation. Ciprofloxacin and metronidazole are the
drugs of choice. Pouch failure may require its excision and permanent terminal ileostomy in about
10% of patients.
Results of Surgery
Patients with a successful RPC/IPAA should have a frequency of 4-6 stools in 24 hours (0-1 at night)
with no/ minimal (to gas/ liquid, at night) incontinence.
UC at SGPGIMS
Between 1989 and 2004, a total of about 400 patients with UC were seen at the SGPGIMS – 91
(23%) required surgery. As many as 53/91 (58%) of patients were on steroids. Mortality was 13/91 for
emergency procedures and 1/40 (2.5%) for elective RPC/IPAA. Leak occurred in 10 cases (pouch 8,
anastomosis 2). 7 out of 47 pouches (14%) failed in the long-term.
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Signs and symptoms of anorectal disorders
Dr. P.N.Agarwal, Nitin Leekha

The anorectum is the terminal portion of the gastrointestinal tract.It is the functional unit that maintains
fecal continence by providing both a stopper-equipped reservoir and a controlled expulsion
mechanism for feces. The rectum is the last and partially extraperitoneal segment of the large
intestine. It starts at the rectosigmoid junction and continues through the pelvic floor into the anal
canal. The nonmobilized rectum is characterized by three distinct endoluminal curves. The resulting
folds that are seen on endoscopy are referred to as the valves of Houston. Definitions of where the
sigmoid colon ends and the rectum begins include: (1) a distance of fifteen centimeters above the
anal verge, (2) the position of the peritoneal reflection, and (3) the level of the sacral promontory. The
most useful landmark from a functional as well as surgical viewpoint is the confluence of the teniae
coli at the rectosigmoid junction1. Because this anatomic reference point cannot be visualized
endoscopically, the National Cancer Institute has defined the rectum as the last twelve centimeters
above the anal verge for the purpose of uniformity in clinical trials 2 .This definition is useful in
preparing for a low anterior resection versus a sigmoid resection, particularly when measured with a
rigid sigmoidoscope.
Definitions of the anal canal also vary among surgeons and anatomists3. The surgical anal canal is
approximately 4 cm long and extends from the anal verge to the anorectal ring, which is defined as
the proximal level of the levator-external anal sphincter complex4. This clinical description correlates
with either a digital or a sonographic examination but does not correspond to the histologic
architecture along the canal. As the rectum narrows into the anal canal, the smooth mucosal lining
changes into a plicated appearance. The columns of Morgagni represent longitudinal folds, which
alternate with pockets 5. The bases of the columns form the anal valves, creating an undulating
demarcation line referred to as the dentate line. It translates into a distance of about 2 cm from the
anal verge. The dentate line marks the point of embryologic fusion and morphologic transition from
endodermal (intestinal) to ectodermal (skin) tissue. This transition is important for the understanding
of the differences in the linings, innervation, arterial and venous blood supply, and the lymphatic
drainage of the anal canal. The bottom of the anal columns represents the origin of the
cryptoglandular complex 6. Four to eight anal glands empty into the anal canal via anal ducts at each
crypt. Anoderm covers the last 1 cm to 1.5 cm of the distal anal canal below the dentate line and
consists of modified squamous epithelium. The intersphincteric groove between the internal and
external anal sphincter can be felt on digitel examination at the same level.
The teleological function of the cryptoglandular complexes (crypt, duct, and anal gland) is unknown.
They vary in number between four and eight and are composed of apocrine glandular elements and
anal ducts . The glands are typically located in the intersphincteric space traversing the internal anal
sphincter. Less frequently, glands may even extend into the external anal sphincter 6. Because the
anal ducts form a one-way conduit for contamination of the perianal and perirectal tissues, their
anatomy forms the bases for cryptoglandular infections and their sequelae, ie, fistula in ano.
Muscles
Muscular structures within the pelvis can be divided into three categories: (1) muscles that line the
sidewalls of the osseous pelvis, (2) muscles of the pelvic floor, and (3) muscles of the anal sphincter
complex. The obturator internus and the piriformis muscle form the external boundary of the pelvis.
Neither one is of importance with regard to anorectal diseases except that they provide an open
communication for pelvic infections to reach extrapelvic tissues. In particular, the posterior midline
cryptoglandular complex can produce infection in the deep postanal space. From this position,
infection can track along the obturator internus fascia to reach the ischioanal space, unilaterally or
bilaterally.
The pelvic floor (pelvic diaphragm) is a funnel-shaped musculotendineous termination of the pelvic
outlet. It is innervated by branches of the ventral primary rami of spinal nerves S3–S4. The pelvic floor
supports the abdominal and pelvic organs, but allows the anorectal and urogenital viscera to pass
through via two hiatal openings. The levator ani muscles form a symmetrical array of paired striated
muscles that originate from the continuous arcus tendineus of the obturator fascia. The latter fascial
structure extends anteroposteriorly from the pubic bone to the ischial spine at the level S3-S4.
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Separate units of the levator ani complex are identified as the ischiococcygeus, iliococcygeus,
pubococcygeous muscle, and puborectalis muscle. The anococcygeal raphe is a fibrous condensation
of the iliococcygeus muscle in the posterior midline and contains fibers that cross over from one side
to the other.
The anal sphincter complex consists of the internal and the external sphincter muscles. Even though
they form a unit, they are distinct in both structure and function. The internal anal sphincter (IAS) is a
specialized smooth muscle condensation in continuation of the circular muscles of the rectum. On
endorectal ultrasound, it appears as a uniform circumferential hypoechogenic ring of 2 mm to 3 mm in
thickness. The IAS is innervated by autonomic sympathetic and parasympathetic nerves. It remains in
a state of continuous contraction and accounts for 50% to 85% of the resting anal tone. In contrast,
the external anal sphincter (EAS) consists of striated skeletal muscle, which is innervated by the
inferior rectal branch of the pudendal nerve. The EAS forms a muscular cylinder that surrounds the
anal canal, including the internal sphincter muscle, on its entire length 4. The distal interface between
the IAS and the EAS forms the intersphincteric groove, which can be palpated approximately 1 cm
below to the dentate line. The classic anatomic viewpoint divides the EAS into subcutaneous,
superficial, and deep components.
Arterial and venous blood supply

The blood supply to the rectum is supplied by two sources: the superior and middle rectal arteries.
The superior rectal artery (superior hemorrhoidal artery) is the terminal branch of the inferior
mesenteric artery. It forms a rich reticular anastomotic network in the rectal submucosa with the
middle rectal artery (middle hemorrhoidal artery). This abundant interconnecting network of dual blood
supplies gives the rectal mucosa its distinct reticular mucosal vascular pattern appreciated in hindgut
endoscopy. The middle rectal arteries originate from the hypogastric (internal iliac) or the inferior
vesicle arteries. They course from the lateral pelvic sidewalls to reach the distal rectum bilaterally
above the level of the levator muscles (pubococcygeus, iliococcygeus). The middle rectal arteries run
a lateral-to-medial course in the pelvis, intertwined with the nervi errigentes.
Some surgical anatomists have emphasized the median sacral artery. It arises from the posterior
surface of the aorta and descends behind the rectum, reaching it at the level of the tip of the coccyx.
On rare occasions, the blood vessel can be the source of bleeding in the posterior mobilization of the
rectum.
The venous drainage of the rectum follows the arterial anatomy. The inferior and middle hemorrhoidal
(rectal) veins ultimately drain into the inferior vena cava via the internal pudendal and hypogastric
veins. The superior rectal vein drains into the portal circulation via the inferior mesenteric vein.
The anorectum receives its major blood supply from the superior and inferior hemorrhoidal arteries
and to a lesser degree from the middle hemorrhoidal artery, forming a wide intramural network of
collaterals. The internal iliac artery gives off a branch to form the extrapelvic pudendal artery. It
accompanies the pudendal nerve through the pudendal canal to continue as the inferior hemorrhoidal
artery.
The venous blood from the anorectum collects in the arteriovenous plexuses. It drains through the
bilateral middle and inferior hemorrhoidal veins and the single superior hemorrhoidal vein, to the
internal iliac vein, and ultimately is a tributary to the inferior vena cava. The external hemorrhoidal
plexus, the correlate for external hemorrhoids, is located in the perianal space below the dentate line.
It communicates with the internal hemorrhoidal plexus—the basis for internal hemorrhoids. It is found
in the submucosal space above the dentate line at the level of the upper anal canal.
Lymphatic drainage
Both the rectum and the anal canal have a rich network of lymphatic plexuses that drain into an
extramural system of lymph channels and nodes. The dentate line represents the interface between
the two different systems of lymphatic drainage. Above the dentate line, lymph drains to the inferior
mesenteric and internal iliac nodes; below the dentate line, lymph drainage proceeds to the superficial
inguinal lymph nodes. Lymph from the upper two thirds of the rectum drains exclusively to the inferior
mesenteric and para-aortic nodes, whereas the lower third of the rectum drains in two directions. One
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is along the superior hemorrhoidal and inferior mesenteric arteries; the other follows the middle
hemorrhoidal vessels laterally to the internal iliac lymph nodes.
Bowel continence
Continence to stool represents a complex interaction of a rather large number of variables. These
variables include stool consistency, reservoir capacity, rectal compliance, achievable sphincter
pressures at rest and at squeeze, and sensation.
Sphincter pressures
The anal sphincter is composed of two major components that provide for normal continence.
Immediately surrounding the canal is the internal anal sphincter, which accounts for approximately
80% to 85% of resting tone. The internal sphincter is involuntary smooth muscle. When performing
anorectal manometry (ARM), the mean maximum resting pressure is largely a measure of internal
sphincter function. Surrounding the internal sphincter is the external sphincter. It is composed of
skeletal muscle. The external sphincter is responsible for enhancement of anal canal pressures during
the process of accommodation and allows for the deferral of the call to stool. The exact structure and
its relationship to the pelvic floor (levator ani) is still open to some debate; however, the puborectalis is
generally felt to represent the superior component of the functional external sphincter unit.
Sensation
Sensory components of the mechanism of continence are critical in allowing an individual a
satisfactory reaction time to react to a bolus of stool or gas entering the rectum. Sensation is
associated with the sampling reflex. This reflex results in the transient relaxation of the internal
sphincter, with contraction of the distal external sphincter, theoretically allowing for discrimination of
the contents of the upper anal canal and rectum as either gas or liquid or solid.9
Constipation
The development of a mass peristaltic wave by the left colon distended with stool results in the
delivery of stool to the lower sigmoid colon and rectum. Once entering the rectum, the reflex
relaxation of the internal sphincter and contraction of the distal external sphincter allows sampling and
maintains continence. Assuming that accommodation does occur, the initial urge to defecate may
pass as intraluminal pressures fall below the tonic resting pressure of the anal canal, so that voluntary
contraction of the external sphincter is not necessary to maintain continence.11
If the urge occurs at a socially acceptable time to proceed with defecation, or if accommodation has
reached its limits and there is little choice as to when to proceed with defecation, the individual will
normally assume a squatting or sitting position. The process of defecation then normally will proceed
with a straightening of the anorectal angle. Normally, intrarectal pressures then rise in response to a
voluntary increase in intra-abdominal pressure due to a Valsalva maneuver. Normally there is a
varying degree of pelvic descent with this maneuver. As rectal pressure increases, there is a
combination of reflex and voluntary relaxation of the external sphincter and reflex relaxation of the
internal sphincter. Once intrarectal pressures rise above the sphincter pressure, defecation can occur.
If this process is accompanied by further mass peristalsis, the entire left colon may be evacuated. If
not, evacuation may occur in a piecemeal fashion, with several defecations occurring in a 24-hour
period. Following defecation, sphincter pressures, intra-abdominal pressure, and the anorectal angle
return to their normal resting pressures and positions.
Constipation manifested as outlet obstruction may occur when any portion of this process is
interrupted. Such situations may occur when there is failure of the puborectalis to relax (paradoxical
puborectalis, anismus, levator syndrome), abnormally high resting pressure (nutcracker anus),
excessive accommodation (megarectum), external compression of the rectum resulting in blockage
(enterocele), incomplete evacuation (large rectocele), or intussusception (overt or covert prolapse). In
addition, excessive pelvic descent may be associated with outlet problems. The exact role of
abnormal pelvic descent is frequently not clear. Whether the descent is a result of chronic straining
due to outlet problems of another etiology or a primary cause of the complaint may be difficult to
determine.10
Proctitis
Proctitis is an inflammation of the lining of the rectum (rectal mucosa). Sexually transmitted diseases
are the most common cause, but other causes include inflammatory bowel diseases, such as
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ulcerative colitis, and non-sexually transmitted infections. Signs and symptoms of proctitis may
include:
 Frequent or continuous urge to have a bowel movement
 Rectal bleeding
 Passing mucus through the rectum
 Anal and rectal pain
 Pain in the lower left abdomen
 A feeling of rectal fullness
 Diarrhea, usually frequent, small amounts
Anorectal Abscess and Fistula

The etiology of anorectal abscess is controversial. The anatomy of most fistulas with an internal
opening at the anal gland in the crypt of Morgagni suggests that these abscesses originate with
infections of the gland 7. British writers felt that such an infection should result in a collection of pus in
the intersphincteric space, between the internal and external sphincter. It is this belief that lead to a
wide internal sphincterectomy being an integral part of the treatment of abscess and fistula in Great
Britain, following the notion that drainage of this space was necessary to resolve sepsis adequately.
Goligher, however when routinely performed sphincterectomy to explore the intersphincteric space,
found very few patients with collection of pus in this region. He felt these were convincing data against
the cryptoglandular origin or anorectal abscess 8.
Fistula in the vast majority of cases arises from pre-existing abscess. Other etiologies of anal fistulae
include superficial fistulae associated with anal fissure and anorectal trauma. The relative frequency
of fistula is described in patients with ulcerative colitis and Crohn's disease 8, though most surgeons
now consider the presence of a fistula indicates that a patient with inflammatory bowel disease does
have Crohn's disease.
TYPES OF FISTULA (CRYPTOGLANDULAR THEORY)
Type 1: Intersphincteric Type 2: Trans-sphincteric Type 3: Supra-sphincteric Type 4: Extra-sphincteric

Goodsall‟s Rule: It states that if the anus is bisected by a line in the frontal plane, an external opening
ant to the line would connect by a short direct fistulous tract to the internal opening, however if the
opening is located posterior to the imaginary line it would connect by a curved course to a crypt in the
posterior midline. An external opening located more than 2 cm from anal verge anterior to the
imaginary line would connect to an internal opening in the posterior midline by a curved tract.
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Giant Condyloma Acuminata
They are rare lesions tending to present in the 5th decade and are two to three times more common
in men than women. They are associated with human papilloma virus types 6 and 11 and risk factors
for their development include anoreceptive intercourse, HIV and immunosuppression. Anorectal GCA
may present as an anal mass, with local symptoms such as bleeding, mucus discharge, sepsis,
pruritus and altered bowel habit, or with systemic symptoms such as weight loss and poor appetite.
Macroscopically they appear as large, cauliflower-like lesions arising in the perineum. Although
microscopically benign, they behave in a malignant fashion, compressing adjacent tissues causing
necrosis and giving the impression of invasion. Histologically, GCA is characterized by undulating
papillomatosis of well-differentiated keratinised epithelium with lymphocytic infiltration. However, these
large lesions may progress to show areas of carcinoma-in-situ or invasive squamous cell carcinoma.
As such, they should be considered to represent a spectrum between simple condyloma acuminatum
and squamous cell carcinoma. Their associated mortality is high, ranging from 20-25% for benign
disease, increasing to 50% in the presence of malignant transformation. Although mortality appears to
be declining with time, probably due to increased understanding and medical and surgical advances,
the incidence of malignant transformation seems to be increasing.
Pruritus Ani
Pruritus ani is defined as an itch localized to the anus and perianal skin and is usually a symptom of
an underlying disorder of the epithelium in that area or of anorectal pathology. Persistent pruritus ani
is a poorly managed, common and socially embarrassing condition.It is one of the commonest
complaint of the patients presenting in rectal clinics.Females are generally more affected than
males.Examination does not correlate well with symptoms.there may not be any findings even with
severe symptoms and vice versa.Sodden white appearance of the perianal skin is characteristic. A
thorough local examination should be carried out.Pruritus ani is often classified as being idiopathic 12
which is more often associated with transient and intermittent symptoms, poor personal
hygiene/soiling and stress 12,13.Patients with secondary pruritus ani generally have more persistent
symptoms, usually with an identifiable cause. Dermatological conditions can be the underlying
problem and the perianal skin may be the only site affected
Treatment consists of treating local pathology. Lotions for local applications that contain short acting
steroids like hydrocortisone. Balls operation involves raisings skin flaps on either side of anus for
about 5 cm. Patients with long-standing pruritus ani with no other symptoms to suggest colorectal
pathology should be referred to a dermatologist for assessment and patch testing.14
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Proctalgia Fugax
 Severe idiopathic intermittent rectal pain of short duration

 Typically like a cramp or spasm starting 5-10 cm above anus
 May vary in intensity and duration
 Cause is not exactly known,may be due to spasm of levater muscle or it may be
psychogenic
Rectal Prolapse
Definition, Cause, and Pathogenesis

A complete rectal prolapse is the protrusion of all layers of the rectal wall through the anal canal. If the
rectal wall has prolapsed but does not protrude through the anus, it is called an occult rectal prolapse
or a rectal intussusception. A rectal prolapse should be distinguished from a mucosal prolapse, in
which there is only protrusion of the rectal or anal mucosa. The incidence of rectal prolapse is highest
among elderly women. In adolescence, the sex ratio is equal.
In the absence of overt neurologic disorders, straining during many years (owing to long-standing
constipation) gradually may weaken the pelvic floor. Consequently, pudendal nerve damage occurs,
and this leads to weakness of the internal and external anal sphincters.15 These pathophysiologic
changes facilitate protrusion of the rectal wall through the anus. Pudendal neuropathy, resulting from
aging or obstetric injury, may play a role16
There are two theories regarding the development of a rectal prolapse. The first theory was proposed
in 1912 by Moschvowitz17. According to this theory, a deep pouch of Douglas allows the small bowel
to protrude into the lower anterior rectal wall. This protrusion together with a mobile mesorectum and
mesosigmoid may allow the development of a rectal prolapse. The second theory was proposed in
1968 by Broden and Snellman.Using cinematography, they suggested that the main cause was an
intussusception from the rectosigmoid region.
Typical anatomical feature of all prolapse are:-
1. The intussusception
2. A deep cul-de-sac or POD
3. Absent fixation of rectum to the sacrum
4. Redundant rectum & sigmoid colon
5. Weakness of pelvis musculature.(This may be secondry to the prolapse itself)
6. Presence of rectocele
Rectal prolapse surgery should correct as many of these possible.
ANAL FISSURE
Fissure in ano or anal fissure is a linera tear in the lining of the distal anal canal below the dentate
line. The classic symptoms are anal pain during or after defecation accompanied by the passage of
bright red blood per anus. The pain often is severe and may last for a few minutes during or persist for
several hours after defecation. Bleeding from an anal fissure usually is modest and separate from the
stool.22
PATHOGENESIS
The pathogenesis of chronic anal fissure is poorly understood. Surgical dogma is that the passage of
a hard stool traumatizes the anal mucosa. This is a plausible initiating factor but does not explain why
only 1 in 4 patients reports constipation, and the onset of symptoms follows a bout of diarrhea in 4%
to 7 % of instances.18,19 There may be a dietary association because individuals consuming a diet
low in fiber appear to be at increased risk of developing anal fissures. Alternative theories of
pathogenesis leading to the development of chronic fissures have been postulated.
Internal Anal Sphincter Hypertonia
The resting pressure in the anal canal is largely a function of the internal sphincter, which is in a
continuous state of partial contraction that is nerve-mediated through alpha-adrenergic pathways and
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caused by inherent myogenic tone.Relaxation of this smooth muscle occurs automatically in response
to rectal distention, the so-called rectoanal inhibitory reflex. Acetylcholine through muscarinic
receptors and beta-adrenergic stimulation mediate relaxation in isolated strips of internal
sphincter.The same effect is observed in response to electric field stimulation through a
nonadrenergic, noncholinergic neuronal pathway, and nitric oxide has been shown to be the
neurotransmitter responsible.
Patients with chronic anal fissures generally have raised resting anal pressures caused by
hypertonicity of the internal anal sphincter, but the causative mechanisms are unclear.20 A long high-
pressure zone in the anal canal and ultraslow waves are seen more commonly in fissure patients than
in healthy controls, and there may be an abnormal rectoanal inhibitory reflex21The administration of
pharmacologic agents that relax the internal anal sphincter, effectively reducing anal canal pressure,
can lead to healing in most chronic fissures. This effect on the muscle appears to be reversible,
however, because resting anal pressures return to pretreatment values after a fissure has
healed.These findings suggest that the internal sphincter hypertonia and consequent anal spasm may
predate the onset of the fissure. The anal spasm probably is not a response to pain because the
application of topical local anesthetic to a fissure alleviates the discomfort but does not reduce the
anal spasm.
Local Ischemia
Chronic anal fissure has been described as an ischemic ulcer. The distal anal canal receives its blood
supply from the inferior rectal arteries, branches of the internal pudendal arteries. In cadaver studies,
angiography of the inferior rectal vessels has shown a paucity of arterioles at the posterior
commissure of the anal canal in 85% of cases, the site for which fissures appear to have a
predilection. Blood flow to the distal anal canal, measured by laser Doppler flowmetry, is correlated
inversely with anal pressure and increases as pressures fall. It has been shown that general
anesthesia, sphincterotomy, and the application of topical glyceryl trinitrate (GTN) ointment in patients
with anal fissure all lower resting anal pressure, while increasing the local tissue perfusion in the distal
anal canal. Because lateral internal sphincterotomy and topical GTN successfully heal 90% and 70%
of fissures, the local blood supply before treatment may have been inadequate for healing to occur. It
is possible that blood vessels traversing the hypertonic internal sphincter en route to the anal mucosa
may be compressed, resulting in compromised perfusion of the anal mucosa and fissure. Because the
spasm in the anal canal in patients with chronic anal fissures appears to predate the fissure, this
would support an ischemic basis for chronic anal fissure and imply that some individuals may be
predisposed toward developing anal fissure.22
Histologic examination of biopsy specimens of internal anal sphincter taken from the base of chronic
fissures and at sites remote from it has shown fibrosis in all regions.This finding has led to the
hypothesis of an underlying inflammatory process in which myositis occurs early on in the condition
with subsequent fibrosis. The fibrosis itself may be secondary to ischemia. Despite various theories,
the cause of chronic anal fissures and the cause of anal spasm associated with the condition remain
somewhat uncertain.
HEMORRHOIDS
Hemorrhoids is a condition that has been known and treated for at least 4000 years24 but has only
recently come to be partially understood. The word hemorrhoid is derived from the Greek adjective
haimorrhoides, which means bleeding (haima = blood; rhoos = flowing). The word pile is derived from
the Latin word pila, meaning a ball. Hemorrhoids usually refer to symptomatic abnormalities of the
normal vascular hemorrhoidal tissue of the anal canal.
The cause of hemorrhoids is not clear, although over the centuries numerous theories abounded25 .By
the middle of the twentieth century, three main theories existed: (1) the varicose vein theory, (2) the
vascular hyperplasia theory, and (3) the concept of a sliding anal lining. The last theory suggests that
hemorrhoidal tissue is the normal lining of the anal canal and that slippage of this lining leads to
symptomatic hemorrhoids26.
Varicose veins were thought to be the cause of hemorrhoids as early as the time of Galen and
Hippocrates. Morgagni further popularized this theory by suggesting that the upright position led to the
development of anal varicosities.27 Work by Thomson and earlier authors showed the venous dilations
362
to be present in infants, suggesting that they are part of normal anal anatomy. The associated
suggestion that low fiber intake, constipation, and straining are important causative factors is not
supported by subsequent work Hemorrhoids are no more common in patients with portal hypertension
than the normal population.Parks suggested that local increases in pressure because of a fecal bolus
caused the varicose swellings; however, the confirmation of the presence of portosystemic
anastomoses contradicts this theory.
During the nineteenth century, several authors suggested that hemorrhoids were a sort of vascular
hyperplastic process.This suggestion was based on the histologic similarities between hemorrhoidal
specimens and other erectile tissues. In 1963, Stelzner proposed the concept of the corpus
cavernosum recti. Thomson and Loder et al pointed out that there are no significant differences in the
vascular anatomy between normal and pathologic hemorrhoidal tissue. Hemorrhoidal bleeding seems
to arise from capillaries in the lamina propria rather than the venous dilations.
If one accepts that hemorrhoidal tissue is the normal lining of the anal canal, symptoms caused by
pathologic slippage of this lining account for the disease known as hemorrhoids. Gass and Adams first
proposed in 1950 that hemorrhoids are caused by slippage of the normal anal canal lining, a theory
later supported by others.Changes in the connective tissue seen in hemorrhoid specimens include
loss of organization, muscular hypertrophy, and fragmentation of the muscle and the elastin
components,When the sliding process has started, shearing forces during defecation tend to
exacerbate the problem. Some data suggest an association between hemorrhoids and hernia and
prolapse of the genitourinary system. Although no hereditary link has been proved, there often is a
strong family history.
Abnormalities of anorectal physiology can be shown in patients with hemorrhoids. Resting anal
pressures are found consistently to be raised. Sun et al reported that the increases in anal resting
pressure were not found in patients with prolapsed hemorrhoids. Other studies did not report this
finding. Some authors postulated that the pressure increase occurs in the vascular beds. After
hemorrhoidectomy, pressures return to normal within 3 months, suggesting the abnormal findings are
a result rather than a cause of the pathology.Rubber band ligation causes only an insignificant
decrease in anal pressure with no return to normal as with surgical treatment.
Ultraslow waves are more common in hemorrhoid sufferers than in normal controls. It is possible that
the ultraslow waves are associated with the high resting pressures and probably originate in the
internal sphincter muscle, although their significance is not clear. Other changes have been recorded
but are less reproducible, including increased external sphincter activity (spike potentials), decreased
anal sensation, and an increased number of sampling responses, At present, the temporal
relationship between these physiologic findings and the development of hemorrhoids is not clear.
Symptoms of carcinoma Rectum
Spurious diarrhea: It the term used for diarrhea of Ca Rectum. Patient is not having diarrhea but is
constipated Patient feels a urgent urge to go to toilet on waking up but passes only blood mixed with
mucous The process of incomplete evacuation is usually repeated 3-4 times till satisfactory complete
evacuation. Patient usually passes 10-12 motions per day.
Tenesmus: Is a greek word meaning ineffective and painful straining at stools.Tenesmus is a spurious
feeling of the need to evacuate the bowels. It may be constant or intermittent. It is usually
accompanied by pain, cramping and involuntary straining efforts, despite which, little or nothing is
passed.
References
1. Stoss F. Investigations of the muscular architecture of the rectosigmoid junction in humans. Dis Colon Rectum
1990;33:378-83.
2. Nelson H, Petrelli N, Carlin A, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst
2001;93:583-96.
3. Wendell-Smith CP. Anorectal nomenclature: fundamental terminology. Dis Colon Rectum 2000;43:1349-58
4. Wexner SD, Jorge JMN. Anatomy and embryology of the anus, rectum, and colon. In: CormanML, editors. Colon
and rectal surgery Philadelphia: Lippincott-Raven; 1998. p. 1-26.
5. Fenger C. The anal transitional zone. Acta Pathologica, Microbiologica, et Immunologica Scandinavica 1987;
289(Supplement):1-42.
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6. Klosterhalfen B, Offner F, Vogel P, et al. Anatomic nature and surgical significance of anal sinus and anal
intramuscular glands. Dis Colon Rectum 1991; 34:156-60.
7. Ramanujam PS, Prasad ML, Abcarian H, et al. Perianal abscess and fistulas; a study of 1023 patients. Dis Colon
Rectum 1984;27:593-7.
8. Hulme-Moir M, Bartolo DC. Hemorrhoids.Gastroenterol Clin North Am. 2001 Mar;30(1):183-97. Review
9. Buser WD, Miner Jr. PB. Delayed rectal sensation with fecal incontinence. Successful treatment using anorectal
manometry. Gastroenterology 1986;91:1186-91.
10. Metcalf AM, Phillips SF, Zinsmeister AR, et al. Simplified assessment of segmental colonic transit.
Gastroenterology 1987;92:40-7.
11. Anorectal physiology Surgical Clinics of North America - Volume 82, Issue 6 (December 2002) -
12. Smith LE, Henrichs D, McCullah RD. Prospective studies on the etiology and treatment of pruritus ani. Dis Colon
Rectum 1982; 25: 358-63.
13. Mazier WP. Hemorrhoids, fissures, and pruritus ani. Surg Clin North Am 1994; 74: 1277-92
14. Dasan S, Neill SM, Donaldson DR, Scott HJ. Treatment of persistent pruritus ani in a combined colorectal and
dermatological clinic. Br J Surg 1999;86:1337–1340.
15. Neill ME, Parks AG, Swash M: Physiological studies of the anal sphincter musculature in faecal incontinence and
rectal prolapse. Br J Surg 68:531, 1981
16. Nicholls J: Rectal prolapse and the solitary ulcer syndrome. In Kamm MA, Lennard-Jones JE (eds): Constipation.
Petersfield UK, Wrightson Biomedical Publishing, 1994, p 289
17. Moschvowitz AV: The pathogenesis, anatomy, and cure of prolapse of the rectum. Surg Gynecol Obstet 15:7,
1912
18. Keighley M, Williams N: Surgery of the Anus, Rectum and Colon. London, WB Saunders
19. Lock MR, Thomson JP: Fissure-in-ano: The initial management and prognosis. Br J Surg 64:355-358,
20. Gibbons CP, Read NW: Anal hypertonia in fissures: Cause or effect? Br J Surg 73:443-445, 1986
21. Hancock BD: The internal sphincter and anal fissure. Br J Surg 64:92-95, 1977
22. Jonas M, Scholefield JH. Anal Fissure.Gastroenterol Clin North Am. 2001 Mar;30(1):167-81
23. Hulme-Moir M, Bartolo DC .Hemorrhoids.Gastroenterol Clin North Am. 2001 Mar;30(1):183-97.
24. Parks AG: De Haemorrhois: A study in surgical history. Guy's Hospital Reports 104:135-156, 1955
25. Thomson WHF: The anatomy and nature of piles. In Kaufman HD (ed): The Haemorrhoids Syndrome. Tunbridge
Wells, Kent, England, Abacus Press, 1981, pp 15-33
26. Thomson WHF: The nature of haemorrhoids. Br J Surg 62:542-552, 1975
27. Morgagni JB: Seats and causes of diseases, Vol 2, Letter 32, Article 10. (Translated by Alexander A.) London, A
Millar, 1769, p 105-106 (quoted in Thomson, 1975
28. Deutsch AA, Moshkovitz M, Nudelman I, et al: Anal pressure measurements in the study of hemorrhoid etiology
and their relation to treatment. Dis Colon Rectum 30:855-857, 1987
29. el-Gendi MA, Abdel-Bakey N: Anorectal pressure in patients with symptomatic hemorrhoids. Dis Colon Rectum
29:388-391, 1986
364

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Index

1. Dr BS Rana Memorial Oration: Computer assisted Robotic Urologic Surgery

2. Intercostal drainage tube management guidelines

3. Chest trauma: Rib fractures and flail chest

5. Management of Liver trauma

6. Tissue biopsy: A surgeon‘s viewpoint

7. Tissue biopsy: techniques and interpretation

8. Surgeon‘s viewpoint: Fluid, electrolytes and blood management

9. Investigations for thyroid disorders

10. Nodular goitre

11. Management of well differentiated thyroid cancers

13. Current management of the complications of portal hypertension: variceal bleeding

14. Is there still a role for surgery in bleeding portal hypertension?

15. Surgery for bleeding varices

16. Role of H.pylori in acid peptic disease

17. Update on GERD diagnosis and management

18. Peptic ulcer disease today

19. Role of surgeon in Acid-Peptic disease

20. Surgery in Acute pancreatitis

21. Treatment options for chronic pancreatitis

22. Choice of surgical procedures for chronic pancreatitis

23. Periampullary carcinoma: surgical management

24. Laparoscopic management of pancreatic diseases

26. Investigations in a patient with early breast cancer

27. Surgical options in early breast cancer

28. Other treatment modalities in early breast cancer

29. Surgery for the early and advanced cases of hypernephroma

30. Other treatment modalities for hypernephroma

31. Management of nephroblastoma

32. Management of cystic lesions of the kidney

33. Surgeons‘ viewpoint: disaster management

34. Genitourinary tuberculosis

35. About HIV

36. Transmission of HIV

37. Prevention of HIV

38. Anti-retroviral therapy for HIV infection

39. Counseling and voluntary testing for HIV / AIDS

40. Investigations for upper limb ischaemia

41. Thoracic outlet syndrome

42. Management of chronic upper limb ischaemia

43. Management of acute upper limb ischaemia

44. Scientific basis of clinical features of intestinal obstruction

45. Congenital ano-rectal anomalies

46. Ileocaecal tuberculosis

47. Surgical complications of amoebiasis

48. Perianal fistulae

49. Pre-operative bowel preparation

50. Pre-malignant conditions of the colon and rectum

51. Management of anal cancers

52. Sphincter saving surgery for rectal cancer

53. Adjuvant therapy for rectal cancers

54. Management of recurrent rectal cancer

55. Surgical management of ulcerative colitis

56. Scientific basis of clinical features of anorectal diseases

Intercostal drainage tube management Management of hyperthyroidism

Surgery for chronic pancreatitis Management of nephroblastoma

Scientific basis of clinical features of Bladder & About HIV

Management of chronic upper limb ischaemia Precancerous conditions

Congenital ano-rectal anomalies Adjuvant therapy for rectal cancers

Dr. Narmada P.Gupta

da Vinci surgical system

(177 Patients, 181 Procedures)

Ablative Reconstructive Miscellaneous

Rad nephrectomy - 7 Radical prostatectomy - 74 Extended Pyelolithotomy -