Research

JAMA Surgery | Original Investigation

A Model for Sustained Collaboration to Address the Unmet

Global Burden of Bladder Exstrophy-Epispadis Complex
and Penopubic Epispadis
The International Bladder Exstrophy Consortium
Rakesh S. Joshi, MD; Dhirendra Shrivastava, MD; Richard Grady, MD; Anjana Kundu, MD;
Jaishri Ramji, MD; Pramod P. Reddy, MD; Joao Luiz Pippi-Salle, MD; Jennifer R. Frazier, MPH;
Douglas A. Canning, MD; Aseem R. Shukla, MD

IMPORTANCE International collaboration to alleviate the massive burden of surgical disease is

recognized by World Health Organization as an urgent need, yet the surgical mission model to
treat reconstructive surgical challenges is often constrained in ensuring adequate patient
follow-up, optimal outcomes, and sustainability.

OBJECTIVE To determine whether a collaboration predicated on long-term commitment by

surgeons returning to the same institution annually combined with an experienced host
surgical team and infrastructure to ensure sustained patient follow-up could provide surgical
care with acceptable outcomes to treat bladder exstrophy-epispadias complex (BE) and
penopubic epispadias (PE).

DESIGN, SETTING, AND PARTICIPANTS In this prospective, observational study, long-term

collaboration was created and based at a public hospital in Ahmedabad, India, between
January 2009 and January 2015. The entire postoperative cohort was recalled in January
2016 for comprehensive examination, measurement of continence outcomes, and
assessment of surgical complications. Seventy-six percent of patients (n = 57) who
underwent complete primary repair of exstrophy during the study interval returned for
annual follow-up in 2016 and formed the study cohort: 23 patients with primary BE, 19
patients with redo BE, and 11 patients with PE repair.

MAIN OUTCOMES AND MEASURES Demographics, operative techniques, and perioperative

complications were recorded. A postoperative protocol outlining procedures to ensure
monitoring of study participants was followed including removal of ureteral stents, urethral
catheter, external fixators, imaging, and patient discharge.

RESULTS Of the 57 patients, median age at time of surgery was 3 years (primary BE), 7 years
(redo BE), and 10 years (PE), with median follow-up of 3 years, 5 years and 3 years,
Author Affiliations: B.J. Medical
respectively; boys made up more than 70% of each cohort (n = 17 for primary BE, n = 15 for
College and Civil Hospital,
redo BE, and n = 9 for PE). All BE and 3 PE repairs (27%) were completed with concurrent Ahmedabad, Gujarat, India (Joshi,
anterior pubic osteotomies. Seventeen of 53 patients (32%) experienced complications. Only Ramji); Gandhi Medical College,
1 patient with BE (4%) had a bladder dehiscence and was repaired the following year. Bhopal, India (Shrivastava); Seattle
Children’s Hospital, Seattle,
Washington (Grady); Dayton
CONCLUSIONS AND RELEVANCE A unique surgical mission model consisting of an international Children’s Hospital, Dayton, Ohio
collaborative focused on treating the complex diagnoses of BE and PE offers outcomes (Kundu); Cincinnati Children’s
Hospital, Cincinnati, Ohio (Reddy);
comparable with those in high-income countries, demonstrating a significant patient
Sidra Medical and Research Center,
retention rate and an opportunity to rigorously study outcomes over an accelerated interval Doha, Qatar (Pippi-Salle); Children’s
owing to the high burden of disease in India. Postoperative care following a systematized Hospital of Philadelphia, Philadelphia,
algorithm and rigorous follow-up is mandatory to ensure safety and optimal outcomes. Pennsylvania (Frazier, Canning,
Shukla).
Corresponding Author: Aseem R.
Shukla, MD, Division of Urology, 3rd
Floor, Wood Bldg, Children’s Hospital
of Philadelphia, 3401 Civic Center
JAMA Surg. doi:10.1001/jamasurg.2018.0067 Blvd, Philadelphia, PA 19104 (shuklaa
Published online March 7, 2018. @email.chop.edu).

(Reprinted) E1
© 2018 American Medical Association. All rights reserved.

Downloaded From: by a Kaohsiung Med Univ User on 03/09/2018

 Research Original Investigation A Sustained Collaboration Model for Bladder Exstrophy-Epispadis Complex and Penopubic Epispadis
T
he bladder exstrophy-epispadias complex (BE) is per-
haps the most profound congenital urologic anomaly,
and the incidence is estimated at 1 in 50 000 live
births. While the number of live births with BE is not known
for India, because there were 25 million live births in that
country in 2013, it may be estimated that 500 infants were
born with the disorder.1 Despite this significant surgical bur-
den, for a geographically diverse and vast nation of 1.2 billion
citizens, comprehensive surgical care required to address BE
is severely limited.2
Surgical collaborations combining the resources and in-
frastructure of academic research centers (ARCs) from higher-
income countries (HICs) with the high volume and local sur-
gical expertise of low- and middle-income country (LMIC)
institutions is 1 strategy to address the surgical burden of BE
in LMICs. We proposed that a long-term collaboration involv-
ing 3 US ARCs, combining with a single large, tertiary medical
center in India, would serve as a clinically rigorous, long-
term, and sustainable model to address the surgical burden
of BE and penopubic epispadias (PE). We posit that such a
collaboration would provide much-needed advanced surgical
care, while accelerating the surgical learning curve to under-
stand the efficacy and outcomes of surgical procedures used.
We also hypothesized that such a dynamic collaboration, that
combines experienced surgical expertise with a committed
and competent host surgical team, would deliver outcomes
that are equivalent and on par with those reported from HIC
ARCs.3
Methods
A multi-institutional collaboration involving surgeons from 2
ARCs from the United States entered into a partnership with
the Department of Pediatric Surgery at the Civil Hospital and
B. J. Medical College in Ahmedabad, India, in 2009. Between
2009 and 2013, the collaboration expanded to consist of
surgeons representing 4 ARCs: Dayton Children’s Hospital,
Dayton, Ohio; Cincinnati Children’s Hospital, Cincinnati, Ohio;
Children’s Hospital of Philadelphia, Philadelphia, Pennsylva-
nia; and Seattle Children’s Hospital, Seattle, Washington. The
Civil Hospital that serves as the host institution for the collab-
orative is a tertiary public hospital financed by the govern-
ment of the state of Gujarat, India, offering free medical care
to a population of more than 60 million people. The memo-
randum of understanding committed the participating insti-
tutions to a long-term collaboration, at least an annual visit of
the same team of surgeons from the United States to India, and
rigorous data collection. All patients treated the previous year
would be recalled for examination each year during the an-
nual surgical team visit, and a comprehensive examination
would be completed.
After obtaining full approval of the Institutional Ethics
Committee of the Civil Hospital, Ahmedabad, and B.J. Medi-
cal College, we received a waiver of consent to retrospec-
tively review the functional, cosmetic, and surgical compli-
cation outcomes of children undergoing primary and redo BE
or isolated PE repair during 8 collaborative events consisting
E2 JAMA Surgery Published online March 7, 2018 (Reprinted)
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Kaohsiung Med Univ User on 03/09/2018
Key Points
Question Can an international surgical collaboration model
address the complex surgical challenge of the bladder
exstrophy-epispadias complex in the developing world in a
sustainable manner with acceptable results?
Findings In this prospective, observational study of 57 children
with bladder exstrophy (n = 42) and isolated penopubic
epispadias (n = 11), a collaboration predicated on long-term
commitment and a competent host team provided outcomes on
par with high-income countries with an acceptable complication
profile.
Meaning A sustained, long-term surgical mission model
collaborating with a host team ensuring rigorous patient follow-up
was associated with improved patient outcomes and an
acceleration of the surgical learning curve for participating
surgeons.
of member institutions between 2009 and 2015. All patients
were recalled in 2016, and data were prospectively collected.
All patients underwent reconstruction using the com-
plete primary repair of exstrophy (CPRE) previously de-
scribed, with modifications including leaving the urethral plate
attached to the glans when possible; cephalotrigonal ureteral
reimplants; and external rotation of corporal bodies.4 Select
CPRE cases and PE cases underwent further tailoring of the
bladder neck by excising redundant tissue at the junction of
the bladder neck and proximal urethra, using the verumonta-
num and mucosal folds present in the distal part of the plate
to confirm location for tapering, and then funneling the blad-
der neck.5 Girls underwent monsplasty aiming to improve geni-
tal cosmesis.
Anterior osteotomies were performed for all BE and PE
cases by 1 of 2 orthopedic surgeons, and external fixators were
applied to stabilize the pubic symphysis after approximation
of the diastasis.
Patient demographic, initial operative techniques, and peri-
operative complications were recorded. General with re-
gional anesthesia was provided by the local anesthesia team
in collaboration with a pediatric anesthesiologist who is a mem-
ber of the US-based team. Lumbar or caudal epidural cath-
eters were placed for all patients who had general anesthesia.
All patients were treated postoperatively by the host surgical
team using a standardized protocol (Figure).
All complications were recorded prospectively and ab-
stracted from the medical record for the purpose of this study
during the annual clinic visit in January 2016. Presence of vesi-
coureteric reflux and bladder capacity was estimated by void-
ing cystourethrogram and urodynamics. Renal scarring was
measured by a nuclear medicine dimercaptosuccinic acid scin-
tigraphy acquired from a private hospital. A surgeon fluent in
the Hindi language, who is not practicing at any of the collab-
orative member institutions, functioned as an unbiased ob-
server, and recorded bladder dry interval timing and admin-
istered the International Consultation on Incontinence Modular
Questionnaire to the parents. Statistical software (SPSS, ver-
sion 24.0 [IBM Corp]) was used to analyze the results. To com-
jamasurgery.com
 A Sustained Collaboration Model for Bladder Exstrophy-Epispadis Complex and Penopubic Epispadis Original Investigation Research

Figure. Postoperative Protocol to Ensure Consistent, Sustainable Care in the First Year After Repair

Consecutive removal of ureteral stents after a trial of capping 2 wk

Removal of urethral catheter 4 wk
Removal of external fixators after radiological imaging 4-5 wk
Discharge after capping of suprapubic catheter 5-6 wk
Recall for an examination under anesthesia and removal of the suprapubic tube,
calibration of the urethra provided upper tract is normal 7-8 wk

Date of surgery 1 mo 2 mo 3 mo 4 mo 5 mo 6 mo 7 mo 8 mo 9 mo 10 mo 11 mo 12 mo

Patients return for monthly

follow-up visits with upper
Patients return at 6, 9, and 12 months for completion of renal
tract imaging completed.
sonography, VCUG, examination under anesthesia, urodynamic
studies, and nuclear scintigraphy. All serum hemotocrit and
electrolyte studies are completed. VCUG indicates voiding
cystourethrogram.

Table 1. Patient and Operative Characteristics, Ahmedabad, India, 2016

Primary BE Redo BE P Value Comparing Primary PE
Characteristics (n = 23) (n = 19) BE and Redo BE (n = 11)
Age at surgery, y
Median (25th to 75th 3 (2.5-6) 7 (4-9) .01a 10 (4-14)
percentiles)
< 3 y At surgery, No. (%) 9 (39) 3 (16) 2 (18)
3-5 y At surgery, No. (%) 8 (35) 7 (37) .19 2 (18)
>5 y At surgery, No. (%) 6 (26) 9 (47) 7 (64)
Sex, No. (%)
Male 17 (74) 15 (79) 9 (82)
Female 6 (26) 4 (21) 2 (18)
.73
Annual follow-up, y
Median (25th to 75th 3 (2-5) 5 (4-7) .004a 3 (2-6)
percentiles)
Operative procedures, No. (%)
Osteotomy 23 (100) 19 (100) 3 (27)
Bladder neck operation 1 (4) 4 (21) 10 (91)
Umbilicoplasty 1 (17) 3 (16) .37 0 Abbreviations: BE, bladder
exstrophy-epispadias complex;
Hernia repair 1 (4) 2 (11) 0
PE, isolated penopubic epispadias.
Reimplantation 1 (4) 3 (16) 1 (9) a
Statistically significant P values.

pare medians between primary BE and redo BE, the Mann-
Whitney U test was used to calculate P values for age, bladder
capacity, and dry intervals. Fisher exact test or Pearson χ2 test
were used to calculate P values for observed measures of sex,
operative procedures, surgical outcomes, and complications.
All P values were 1-sided, and the P value level of significance
was .01.
Results
The collaboration performed a total of 75 BE and PE surgical
reconstructions during the study interval, from January
2009 to January 2015. All patients were contacted for exten-
sive examination, patient interviews, continence assess-
ment, and completion of questionnaires in January 2016
and again in January 2017. One mortality occurred in the
second year of the collaboration after a BE repair, 3 weeks
postsurgery, owing to septicemia. A total of 57 (76%)
returned for the January 2016 follow-up evaluation and
make up the cohort of this study.
Of the 53 patients who are included in this study, the co-
hort consists of 42 BE cases (32 boys and 10 girls), with 23 pri-
mary BE repairs and 19 redo BE reconstructions. Of the 19 pa-
tients with redo BE, 1 was a failed primary repair completed
during a collaborative visit and was revised by the same sur-
gical team in the subsequent year. The remaining 18 redo re-
pairs had undergone primary BE at outside hospitals. A total
of 11 PE repairs make up the remainder of the study cohort. Me-
dian age was 3 years for patients with primary BE, 7 years for
patients with redo BE, and 10 years for patients with PE. Fol-
low-up intervals were 3 years for patients with BE, 5 years for
patients with redo BE, and 3 years for patients with redo PE.
Additional patient characteristics and initial operative proce-
dures are listed in Table 1.
All patients undergoing BE repair and 3 patients undergo-
ing PE repair (27%) underwent anterior pelvic osteotomies at
the time of reconstruction. All patients received appropriate

jamasurgery.com (Reprinted) JAMA Surgery Published online March 7, 2018 E3

© 2018 American Medical Association. All rights reserved.

Downloaded From: by a Kaohsiung Med Univ User on 03/09/2018

 Research Original Investigation A Sustained Collaboration Model for Bladder Exstrophy-Epispadis Complex and Penopubic Epispadis

Table 2. Surgical Outcomes, Ahmedabad, India, 2016

P value
No. (%) Comparing
Primary BE Redo BE Primary BE and
Renal Function Outcome (n = 23) (n = 19) Redo BE PE, No. (%) (n = 11)
VUR 19 (83) 18 (95) 1 (9)
Bilateral VUR 10 (52) 14 (78) 1 (100)
.50
Unilateral VUR 9 (47) 4 (22) 0
Hydronephrosis 2 (9) 4 (21) NA 0
Renal scarring 6 (26) 7 (37) NA 0
Estimated bladder capacity (measured by
VCUG and urodynamics)
Median bladder capacity, 25th to 75th 30 (20-50) 40 (20-60) .29 120 (60-180)
percentiles, mL
<30 mL 10 (44) 6 (32) 0
30-50 mL 9 (39) 6 (32) 3 (27)
.35
>50 mL 4 (17) 7 (37) 8 (73)
Hypospadic meatus placement post-CPRE (n = 6) (n = 7) (n = 9)
Penoscrotal 3 (50) 4 (57) 7 (78)
Mid-shaft 2 (33) 1 (14) 0
.69
Subcoronal 1 (17) 2 (29) 2 (22)
Complications (n = 23) (n = 19) (n = 11)
Superficial skin infection 2 (9) 3 (16) 0
Bladder outlet obstruction 1 (4) 0 0
Abbreviations: BE, bladder
Dehiscence 1 (4) 0 0 exstrophy-epispadias complex;
Deep wound infection requiring 0 1 (5) .99 1 (9) CPRE, complete primary repair of
debridement exstrophy; NA, not applicable;
Fistula 3 (13) 4 (21) 0 PE, isolated penopubic epispadias;
VCUG, voiding cystourethrogram;
Peroneal nerve palsy 1 (4) 0 0
VUR, vesicoureteral reflex.

blood transfustions during surgery. A formal bladder neck ta-
pering with funneling of the bladder neck, as previously de-
scribed, was completed for 1 primary and 4 redo BE repairs and
for 10 of 11 PE repairs (91%). During the study interval and fol-
lowing initial repairs, 1 child with primary BE repair and 3 chil-
dren with redo BE repair underwent ureteral reimplantation
owing to vesicoureteral reflux causing dilation of the upper
tracts, and 3 patients from the BE cohort had inguinal hernia
repairs. Two patients developed transient ischemia after
pubic approximation that resolved once a diastasis of 1.5 cm
was preserved intraoperatively. There were no penile or
glans losses as a result of these ischemic episodes within the
study cohort.
Table 2 displays surgical outcomes for BE and PE repairs,
including the presence or absence of upper urinary tract dila-
tion, presence of vesicoureteral reflux, renal scarring, and blad-
der capacity. Complications are also presented.
Of 6 patients developing de novo hydronephrosis, it was
nonobstructive in 5, but 1 female patient with redo BE devel-
oped bladder outlet obstruction causing upper urinary tract
dilation and was placed on clean intermittent catheteriza-
tion. Median and maximum bladder capacity assessed post-
operatively after repair is provided in Table 2. The epispadias
reconstruction as a concurrent part of the CPRE repair left a
hypospadic meatus in 6 primary BE and 7 redo BE cases.
Surgical complications occurred in 32% of patients with
BE and PE (n = 17) and are listed in Table 2, stratified by pri-
mary BE, redo BE, and PE cases. A fistula occurred in patients
with primary BE (n = 3) and redo BE (n = 4), 5 of which healed
spontaneously over time, leaving 2 needing medical interven-
tion. One patient had transient peroneal nerve palsy after their
single osteotomy procedure and was successfully treated with
physical therapy. Continence outcomes were measured by the
patient/parent-reported length of dry interval and also by re-
sults of the International Consultation on Incontinence Modu-
lar Questionnaire questionnaire (Table 3). Seventeen percent
of patients with primary BE (n = 4) and 32% of patients with
redo BE (n = 6) achieved dry intervals greater than 90 min-
utes. The median age of children with the longest dry inter-
val was 4.5 years for primary BE repairs and 13 years for redo
BE repairs, and a trend toward improving continence with in-
creasing age was noted.
Discussion
While the data on the incidence and country-specific differ-
ences in congenital anomalies in LMICs are sparse, it is clear
that access to specialty surgical care to address specific con-
genital anomalies requiring complex surgical reconstruction
is fraught.6,7 The burden of congenital anomalies falls most
heavily on LMICs, where 94% of anomalies occur.3 Bladder ex-
strophy-epispadias complex causes stigma, which can trig-
ger abandonment or isolation of an entire family owing to the
socially isolating issues of foul-smelling urine, lack of urinary-
absorptive clothing, and access to clean laundry facilities.8
We used the surgical mission model to provide care at
the Civil Hospital in Ahmedabad, India. While many such

E4 JAMA Surgery Published online March 7, 2018 (Reprinted) jamasurgery.com

© 2018 American Medical Association. All rights reserved.

Downloaded From: by a Kaohsiung Med Univ User on 03/09/2018

 A Sustained Collaboration Model for Bladder Exstrophy-Epispadis Complex and Penopubic Epispadis
Table 3. Parent-Reported Continence Outcomes, Ahmedabad, India, 2016
No. (%)
Continence Outcome Primary BE (n = 19)
Incontinence, leakage frequency
Never 1 (5)
≤1 per wk 1 (5)
2-3 per wk 0 4 (22)
1 per d 7 (37)
All the time 10 (53)
Dry intervals and age, median (25th to 75th (n = 23)
percentiles)
Dry interval, min, median (25th to 75th percentiles) 35 (10-45)
Dry interval <30 min
Age, y, median (IQR) 3 (1.7-5.3)
Total patients, No. (%) 12 (52)
Dry interval 30-90 min
Age, y, median (IQR) 5 (3-7)
Total patients, No. (%) 7 (35)
Dry interval >90 min
Age, y, median (IQR) 5 (2.7-12)
Total patients, No. (%) 4 (17)
missions or humanitarian volunteer trip paradigms are short
term and often rotating at different institutions with varying
team members, the model we use differs in that it joins an or-
ganized consistent team of the same experienced pediatric
urologists and pediatric anesthesiologist supported by 3 US
institutions to deliver care in an LMIC nation context.9 Our
mission is also unique in that it is predicated on a long-term
commitment, now into its 10th year, and also leverages
an experienced host surgical team, perioperative team,
and institution that has also benefited from the extended
relationship.
Commonly proffered criticisms and real limitations of col-
laborations focused on genitourinary reconstruction include
lack of capacity with the partnering host institution to pro-
vide advanced postoperative care and address potentially sig-
nificant morbidities; lack of anesthesia and pain manage-
ment competency; absence of a long-term commitment to
return to the same institution; and lack of a sustained fol-
low-up care model to ensure that the long-term conse-
quences of even successful BE closure are addressed.
The aforementioned critiques are certainly valid, and
addressing these prospectively was crucial prior to moving for-
ward with this collaboration. This collaboration joined with the
second largest hospital in Asia, and its pediatric surgery de-
partment oversees 100 beds and performed 6780 surgical pro-
cedures per year and was therefore assessed to possess the
capacity to care for postoperative patients with BE and PE.
When surgical care is available, risks ranging from lack of
postoperative care competencies to the access and provision
of anesthetic care raises surgical morbidity and mortality sig-
nificantly in LICs.10 While mortality exclusively attributed to
anesthesia-related complications is 25 deaths per million an-
esthetics in Organisation for Economic Co-operation and De-
velopment nations, that rate is 141 per million in LMICs.11 The
mortality rate for BE surgery in the United States approaches
jamasurgery.com
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Kaohsiung Med Univ User on 03/09/2018
Original Investigation Research
Redo BE (n = 18) PE (n = 10)
1 (6) 4 (40)
1 (6) 2 (20)
1 (10)
4 (22) 1 (10)
8 (44) 2 (20)
(n = 19) (n = 11)
30 (10-90) 110 (50-120)
5 (3-8) 4 (NA)
9 (47) 2 (18)
7 (4.3-8.8) 6 (NA)
4 (21) 2 (18)
8 (4.3-13) 11 (10-14) Abbreviations: BE, bladder
exstrophy-epispadias complex;
6 (32) 7 (64)
PE, isolated penopubic epispadias.
1.5%, especially in preterm infants, and in this collaborative
experience, we experienced a single mortality 6 months after
surgery in an 8-month-old child.12 Postmortem study was
not completed because the mortality occurred in a distant
village, but upper tract imaging and other parameters were nor-
mal on 2 follow-up studies prior to the mortality, and the in-
fant died after prolonged diarrhea and dehydration as per the
family. We believe that rigorous postoperative care as per a
systematized protocol, including frequent upper tract imaging,
minimizes the risk of perioperative catastrophic complica-
tions, and we continue to abide by rigorous standards to
preclude mortality as an urgent priority.
Commonly described perioperative complications and
morbidity of BE and PE repair include the risk of complete
dehiscence after repair, superficial wound infection, urethro-
cutaneous or penopubic fistula, urinary tract infection, and
bladder outlet obstruction. We experienced 1 bladder dehis-
cence, or failed closure, of 42 patients undergoing BE repair
(2.3%). The comparable reported incidence in US-based stud-
ies varies from 8% to 29.5% and may be associated with vari-
ous risk factors.13,14 A large series of 156 primary BE repairs over
25 years demonstrated wound dehiscence with bladder pro-
lapse in 46 patients and. on multivariate analysis, found that
timing and performance of osteotomy as well as length of im-
mobilization significantly reduced the risk of bladder
prolapse.14 Our relatively low risk of bladder dehiscence may
be attributed to a prospective decision to perform an anterior
osteotomy in all patients undergoing BE repair and immobi-
lize all patients with an external fixator for 4 to 5 weeks.
Penile ischemia is a well-reported sequela of the CPRE,
likely owing to a compartment syndrome affecting the corpo-
ral bodies after internal rotation of the pubic symphysis
during the repair.15 Extensive pubic approximation after os-
teotomies deserves special attention because in some cases it
can lead to compartment syndrome and penile ischemia. In 2
(Reprinted) JAMA Surgery Published online March 7, 2018 E5
 Research Original Investigation A Sustained Collaboration Model for Bladder Exstrophy-Epispadis Complex and Penopubic Epispadis
cases in this series, we were able to identify and document
significant ischemia when full pubic approximation was
done. In such cases, gradual release of the suture approxi-
mating the pubis recovered penile supply, avoiding ische-
mia and genital loss.
Penopubic fistula formation can occur in approximately
15% of all children undergoing the CPRE for BE repair, and the
incidence in our experience is similar at 17% (7 of 42 BE
repairs).13 While penopubic fistula is a challenging complica-
tion that often requires a complex revision of the epispadias
portion of the repair with repeated mobilization of the corpo-
ral bodies, in our experience, 5 of the fistulas closed sponta-
neously as long as a suprapubic tube was left in place to di-
vert urinary drainage. The visible fistulas had closed prior to
discharge from the host institution after the external fixators
were removed at 4 to 5 weeks following surgery.
Bladder outlet obstruction is a devastating complication
after BE and PE repair. The etiology of this complication is un-
clear, but aggressive tailoring at the bladder neck, whether dur-
ing a CPRE or staged approach or a compartment syndrome
effect causing vascular compromise in the deep pelvis after
complete reapproximation of the pubic symphysis after oste-
otomies, are potential factors.5 The obstruction at the ure-
thra or bladder neck presents an immediate danger to the up-
per urinary tract, leads to urinary tract infections, and is
difficult to definitively treat.16 One girl developed this com-
plication, and upper urinary tract dilation was documented.
This child is undergoing clean intermittent catheterization and
close follow-up.
Urinary incontinence is a common sequelae of BE repair,
and the long-term continence rate after CPRE varies from 20%
to 50%, depending on whether additional reconstructive
procedures are undertaken.13 Ellison et al,14 using a strict defi-
nition of continence as dry intervals of 3 hours or longer, dem-
onstrated that 5 of 29 children (17.2%) were continent after the
CPRE alone without additional bladder neck surgery and that
continence is often achieved well into adolescence.14 Our ex-
perience approaches, but does not match, the results in the pre-
viously cited report because we report dry intervals of at least
90 minutes in 10 of 42 children (24%) undergoing BE repair,
without any additional surgical intervention. A similar num-
ber of patients (18 of 37) self-reported nearly continuous
urinary dribbling with activity and may require ancillary in-
terventions (Table 3). It should be noted that our experience
includes 19 redo exstrophy repairs associated with poor long-
term continence and that we continue to monitor these chil-
dren with stable upper tracts to evaluate continence out-
comes as they approach adolescence.17,18 However, continence
is a reasonable expectation after PE repair, with published con-
tinence rates approaching 75% and our own finding of 73%.19
Additionally, consistent with Ellison et al,14 we noted a trend
toward improved continence with older age.14
As of January 2016, we gradually began measuring the
width of the bladder plate corresponding to the bladder neck
location determined by longitudinal mucosal folds and the lo-
cation of the verumontanum. We now tailor that bladder neck
and funnel it to approximately 17 mm. We await longer-term
results to assess the outcome of this novel intervention.
E6 JAMA Surgery Published online March 7, 2018 (Reprinted)
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Kaohsiung Med Univ User on 03/09/2018
Short-term surgical missions notoriously have variability
in surgical teams and competencies as well as poor patient re-
tention and follow-up. One study following 4100 cleft lip op-
erations performed by short-term surgical missions20 found
that only 17.1% of the patients returned for postoperative
follow-up. We prospectively constructed this collaboration
to include a long-term commitment, now into its 10th year,
and we also instituted rigorous preoperative counseling,
setting expectations of care and a mechanism that not only
ensured that patients returned for follow-up but also that
they underwent a comprehensive examination. Our 76%
patient retention rate, despite various LMIC challenges in
transportation and communications methods, confirms the
success of our approach and diverges from previously pub-
lished experiences.
Perhaps the most rewarding outcome of this endeavor has
been the opportunity to evaluate results and institute out-
come improvement initiatives resulting from the accumu-
lated experience gained in treating a large cohort with a rare
anomaly. Indeed, as a direct result of an evaluation of the re-
sults presented herein, to maximize results without compro-
mising safety, we now perform prospective surgical interven-
tions such as formal bladder neck tapering at time of CPRE to
improve continence; bilateral cephalotrigonal reimplants to re-
duce the prevalence of VUR, carefully assessing penile vascu-
larity at time of approximation of pubic symphysis, leaving a
small diastasis that is covered with rectus fascial flaps when
penile ischemia as seen with 2 of our patients; external rota-
tion of corporal bodies to minimize ventral chordee21; rota-
tional pedicle skin flap for skin coverage22; and a monsplasty
for female patients to improve the genital appearance.23 These
operative modifications to the repair of BE and PE are now
being implemented at the US-based institutions as well, a di-
rect result of collaboration.
Limitations
We acknowledge limitations inherent in any retrospective
cohort study. Although demographic variables (age, primary,
and redo BE repairs) were comparable between the primary
and redo BE groups, it is possible that unforeseen confound-
ing variables may have influenced our results. We also ac-
knowledge that this study is insufficiently powered and
requires even longer-term follow-up to evaluate continence
rates, arguably a crucial outcome measure in evaluating the
CPRE procedure. Our collaborative is committed to continu-
ing the surgical visits, leveraging resources to ensure im-
proved patient retention and evaluation, and minimizing
morbidity and mortality that are risks of highly complex re-
constructive surgery. Central to this mission remains, of course,
the shared goal to enhance the quality of life for the affected
individuals.
Conclusions
A multi-institutional collaborative composed of institutions
based in HIC and LIMC contexts that leverages capabilities and
recognizes limitations is a feasible and sustainable model for
jamasurgery.com
 A Sustained Collaboration Model for Bladder Exstrophy-Epispadis Complex and Penopubic Epispadis
alleviating the global burden of surgical disease. We propose
that this collaborative focused on BE and PE with a signifi-
cant patient retention rate affords an opportunity to rigor-
ARTICLE INFORMATION
Accepted for Publication: December 28, 2017.
Published Online: March 7, 2018.
doi:10.1001/jamasurg.2018.0067
Author Contributions: Dr Shukla had full access to
all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the
data analysis.
Concept and design: Joshi, Grady, Kundu, Reddy,
Pippi-Salle, Canning, Shukla.
Acquisition, analysis, or interpretation of data:
Joshi, Shrivastava, Grady, Ramji, Reddy, Frazier,
Shukla.
Drafting of the manuscript: Shrivastava, Reddy,
Frazier, Shukla.
Critical revision of the manuscript for important
intellectual content: Joshi, Grady, Kundu, Ramji,
Reddy, Pippi-Salle, Canning, Shukla.
Statistical analysis: Joshi, Shrivastava, Reddy,
Frazier, Shukla.
Obtained funding: Canning, Shukla.
Administrative, technical, or material support: Joshi,
Shrivastava, Kundu, Ramji, Canning, Shukla.
Supervision: Joshi, Ramji, Pippi-Salle, Canning,
Shukla.
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank M. M.
Prabhakar, MD, superintendent of Civil Hospital, for
his unequivocal support of the collaboration as
host, and provision of resources to enable an
undertaking of this magnitude. The late Atul
Thakre, MS, articulated the vision and identified the
need for this collaboration and P. B. Dave, MS, S.
Chandna, MCh, and B. J. Shah, MD, (Civil Hospital
and BJ Medical College, Ahmedabad, Gujarat,
India), offered crucial initial encouragement and
guidance. The Children’s Hospital of Philadelphia,
Cincinnati Children’s Hospital, and International
Volunteers in Urology and Hindu American
Physicians in Seva provided crucial financial and
logistical support. We acknowledge the enthusiastic
support of the Association for Bladder Exstrophy
Community and the in-country child-life support of
the executive director, Pamela Block. Vinod
Gautam, MS, and Piyush Mittal, MS (Civil Hospital
and BJ Medical College, Ahmedabad, Gujarat,
India), provided expert and invaluable orthopedic
surgical services to all patients. No compensation
was received from any funding sponsor.
Finally, this collaborative would never have been
initiated and cultivated if not for the commitment
of the late Richard Grady, MD, of Seattle Children’s
Hospital. Dr Grady’s global renown as a surgical
innovator, pioneer of bladder exstrophy surgery,
gifted teacher, and commitment to global medicine
awes, even as it inspires, the very basis of this
jamasurgery.com
© 2018 American Medical Association. All rights reserved.
Downloaded From: by a Kaohsiung Med Univ User on 03/09/2018
ously study outcomes achieved after the CPRE over an accel-
erated interval owing to the high burden of disease at a public
hospital in India.
collaborative.
Additional Information: Deceased: Richard Grady,
MD.
REFERENCES
1. UNICEF. Statistics. https://www.unicef.org
/infobycountry/india_statistics.html. Published
December 27, 2013. Accessed August 14, 2017.
2. Bhatnagar V. The management of bladder
exstrophy: Indian scenario. J Indian Assoc Pediatr
Surg. 2011;16(2):43-44.
3. World Health Organization. Congenital
anomalies: 2012 fact sheet No. 370, WHO, Geneva.
http://www.who.int/mediacentre/factsheets/fs370
/en/. Accessed June 12, 2017.
4. Grady RW, Mitchell ME. Complete primary repair
of exstrophy. J Urol. 1999;162(4):1415-1420.
5. Borer JG, Vasquez E, Canning DA, et al.
Short-term outcomes of the multi-institutional
bladder exstrophy consortium: successes and
complications in the first two years of collaboration.
J Pediatr Urol. 2017;13(3):275.e1-275.e6.
6. Centers for Disease Control and Prevention.
2012. Birth defects. https://www.cdc.gov/ncbddd
/birthdefects/index.html. Published 2012. Accessed
June 12, 2017.
7. Christianson AL, Howson CP, Modell B. Global
Report on Birth Defects: The Hidden Toll of Dying
and Disabled Children. White Plains, NY: March of
Dimes Birth Defects Foundation; 2006.
8. Farmer D, Sitkin N, Lofberg K, et al. Surgical
interventions for congenital anomalies. In: Debas
HT, Gawande A, Jamison DT, Kruk ME, Mock CN,
eds. Disease Control Priorities, Third Edition, Volume
1, Essential Surgery. Washington, DC: World Bank;
2015: 129-150.
9. Martiniuk ALC, Manouchehrian M, Negin JA, Zwi
AB. Brain gains: a literature review of medical
missions to low and middle-income countries. BMC
Health Serv Res. 2012;12:134.
10. Högberg U. Maternal deaths related to
cesarean section in Sweden, 1951-1980. Acta Obstet
Gynecol Scand. 1989;68(4):351-357.
11. Weiser T, Gawande A. Excess surgical mortality:
strategies for improving quality of care. In: Debas
HT, Gawande A, Jamison DT, Kruk ME, Mock CN,
eds. Disease Control Priorities, Third Edition, Volume
1, Essential Surgery. Washington, DC: World Bank;
2015: 279-306.
12. Bainbridge D, Martin J, Arango M, Cheng D;
Evidence-based Peri-operative Clinical Outcomes
Research (EPiCOR) Group. Perioperative and
anaesthetic-related mortality in developed and
(Reprinted) JAMA Surgery Published online March 7, 2018
Original Investigation Research
developing countries: a systematic review and
meta-analysis. Lancet. 2012;380(9847):1075-1081.
13. Nelson CP, Dunn RL, Wei JT, Gearhart JP.
Surgical repair of bladder exstrophy in the modern
era: contemporary practice patterns and the role of
hospital case volume. J Urol. 2005;174(3):1099-1102.
14. Ellison JS, Shnorhavorian M,
Willihnganz-Lawson K, Grady R, Merguerian PA.
A critical appraisal of continence in bladder
exstrophy: long-term outcomes of the complete
primary repair. J Pediatr Urol. 2016;12(4):
205.e1-205.e7.
15. Cervellione RM, Husmann DA, Bivalacqua TJ,
Sponseller PD, Gearhart JP. Penile ischemic injury in
the exstrophy/epispadias spectrum: new insights
and possible mechanisms. J Pediatr Urol. 2010;6(5):
450-456.
16. Sirisreetreerux P, Lue KM, Ingviya T, et al. Failed
primary bladder exstrophy closure with osteotomy:
multivariable analysis of a 25-year experience. J Urol.
2016;5347:31440.
17. Baker LA, Jeffs RD, Gearhart JP. Urethral
obstruction after primary exstrophy closure: what is
the fate of the genitourinary tract? J Urol. 1999;161
(2):618-621.
18. Ebert AK, Schott G, Bals-Pratsch M, Seifert B,
Rösch WH. Long-term follow-up of male patients
after reconstruction of the bladder-exstrophy-
epispadias complex: psychosocial status,
continence, renal and genital function. J Pediatr Urol.
2010;6(1):6-10.
19. Spinoit AF, Claeys T, Bruneel E, Ploumidis A,
Van Laecke E, Hoebeke P. Isolated male epispadias:
anatomic functional restoration is the primary goal.
Biomed Res Int. 2016;2016:6983109.
20. Bermudez L, Carter V, Magee W Jr, Sherman R,
Ayala R. Surgical outcomes auditing systems in
humanitarian organizations. World J Surg. 2010;34
(3):403-410.
21. Baka-Jakubiak M. Combined bladder neck,
urethral and penile reconstruction in boys with the
exstrophy-epispadias complex. BJU Int. 2000;86
(4):513-518.
22. Pippi Salle JL, Jednak R, Capolicchio JP, França
IM, Labbie A, Gosalbez R. A ventral rotational skin
flap to improve cosmesis and avoid chordee
recurrence in epispadias repair. BJU Int. 2002;90
(9):918-923.
23. Cook AJ, Farhat WA, Cartwright LM, Khoury AE,
Pippi Salle JL. Simplified mons plasty: a new
technique to improve cosmesis in females with the
exstrophy-epispadias complex. J Urol. 2005;173(6):
2117-2120.
E7