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Joshi RS, Shrivastava D, Grady R, et al. A Model for Sustained Collaboration to Address the Unmet Global Burden of Bladder Exstrophy-Epispadias Complex and Penopubic Epispadias: The International Bladder Exstrophy Consortium. JAMA Surg. 2018;153(7):618–624. doi:10.1001/jamasurg.2018.0067
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?
In this prospective, observational study of 53 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.
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.
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.
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.
Of the 57 patients, 4 were excluded because they underwent ureterosigmoidostomy. 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, respectively; boys made up more than 70% of each cohort (n = 17 for primary BE, n = 15 for redo BE, and n = 9 for PE). All BE and 3 PE repairs (27%) were completed with concurrent anterior pubic osteotomies. Seventeen of 53 patients (32%) experienced complications. Only 1 patient with BE (4%) had a bladder dehiscence and was repaired the following year.
Conclusions and Relevance
A unique surgical mission model consisting of an international collaborative focused on treating the complex diagnoses of BE and PE offers outcomes comparable with those in high-income countries, demonstrating a significant patient retention rate and an opportunity to rigorously study outcomes over an accelerated interval owing to the high burden of disease in India. Postoperative care following a systematized algorithm and rigorous follow-up is mandatory to ensure safety and optimal outcomes.
The bladder exstrophy-epispadias complex (BE) is perhaps 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 burden, 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 infrastructure of academic research centers (ARCs) from higher-income countries (HICs) with the high volume and local surgical 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 involving 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 understand 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
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, Pennsylvania; and Seattle Children’s Hospital, Seattle, Washington. The Civil Hospital that serves as the host institution for the collaborative is a tertiary public hospital financed by the government of the state of Gujarat, India, offering free medical care to a population of more than 60 million people. The memorandum of understanding committed the participating institutions 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 annual 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. Medical College, we received a waiver of consent to retrospectively review the functional, cosmetic, and surgical complication outcomes of children undergoing primary and redo BE or isolated PE repair during 8 collaborative events consisting of member institutions between 2009 and 2015. All patients were recalled in 2016, and data were prospectively collected.
All patients underwent reconstruction using the complete primary repair of exstrophy (CPRE) previously described, 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 verumontanum and mucosal folds present in the distal part of the plate to confirm location for tapering, and then funneling the bladder neck.5 Girls underwent monsplasty aiming to improve genital 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 perioperative complications were recorded. General with regional anesthesia was provided by the local anesthesia team in collaboration with a pediatric anesthesiologist who is a member of the US-based team. Lumbar or caudal epidural catheters 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 abstracted from the medical record for the purpose of this study during the annual clinic visit in January 2016. Presence of vesicoureteric reflux and bladder capacity was estimated by voiding cystourethrogram and urodynamics. Renal scarring was measured by a nuclear medicine dimercaptosuccinic acid scintigraphy acquired from a private hospital. A surgeon fluent in the Hindi language, who is not practicing at any of the collaborative member institutions, functioned as an unbiased observer, and recorded bladder dry interval timing and administered the International Consultation on Incontinence Modular Questionnaire to the parents. Statistical software (SPSS, version 24.0 [IBM Corp]) was used to analyze the results. To compare 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.
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 extensive examination, patient interviews, continence assessment, 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 cohort consists of 42 BE cases (32 boys and 10 girls), with 23 primary BE repairs and 19 redo BE reconstructions. Of the 19 patients with redo BE, 1 was a failed primary repair completed during a collaborative visit and was revised by the same surgical team in the subsequent year. The remaining 18 redo repairs had undergone primary BE at outside hospitals. A total of 11 PE repairs make up the remainder of the study cohort. Median age was 3 years for patients with primary BE, 7 years for patients with redo BE, and 10 years for patients with PE. Follow-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 procedures are listed in Table 1.
All patients undergoing BE repair and 3 patients undergoing PE repair (27%) underwent anterior pelvic osteotomies at the time of reconstruction. All patients received appropriate blood transfustions during surgery. A formal bladder neck tapering with funneling of the bladder neck, as previously described, was completed for 1 primary and 4 redo BE repairs and for 10 of 11 PE repairs (91%). During the study interval and following initial repairs, 1 child with primary BE repair and 3 children 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 dilation, presence of vesicoureteral reflux, renal scarring, and bladder capacity. Complications are also presented.
Of 6 patients developing de novo hydronephrosis, it was nonobstructive in 5, but 1 female patient with redo BE developed bladder outlet obstruction causing upper urinary tract dilation and was placed on clean intermittent catheterization. Median and maximum bladder capacity assessed postoperatively 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 primary 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 intervention. 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 results of the International Consultation on Incontinence Modular 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 minutes. The median age of children with the longest dry interval was 4.5 years for primary BE repairs and 13 years for redo BE repairs, and a trend toward improving continence with increasing age was noted.
While the data on the incidence and country-specific differences in congenital anomalies in LMICs are sparse, it is clear that access to specialty surgical care to address specific congenital 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 exstrophy-epispadias complex causes stigma, which can trigger 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 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 organized 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 collaborations focused on genitourinary reconstruction include lack of capacity with the partnering host institution to provide advanced postoperative care and address potentially significant morbidities; lack of anesthesia and pain management competency; absence of a long-term commitment to return to the same institution; and lack of a sustained follow-up care model to ensure that the long-term consequences of even successful BE closure are addressed.
The aforementioned critiques are certainly valid, and addressing these prospectively was crucial prior to moving forward with this collaboration. This collaboration joined with the second largest hospital in Asia, and its pediatric surgery department oversees 100 beds and performed 6780 surgical procedures 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 significantly in LICs.10 While mortality exclusively attributed to anesthesia-related complications is 25 deaths per million anesthetics in Organisation for Economic Co-operation and Development nations, that rate is 141 per million in LMICs.11 The mortality rate for BE surgery in the United States approaches 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 normal on 2 follow-up studies prior to the mortality, and the infant 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 complications, 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, urethrocutaneous or penopubic fistula, urinary tract infection, and bladder outlet obstruction. We experienced 1 bladder dehiscence, or failed closure, of 42 patients undergoing BE repair (2.3%). The comparable reported incidence in US-based studies varies from 8% to 29.5% and may be associated with various risk factors.13,14 A large series of 156 primary BE repairs over 25 years demonstrated wound dehiscence with bladder prolapse in 46 patients and. on multivariate analysis, found that timing and performance of osteotomy as well as length of immobilization 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 immobilize 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 corporal bodies after internal rotation of the pubic symphysis during the repair.15 Extensive pubic approximation after osteotomies deserves special attention because in some cases it can lead to compartment syndrome and penile ischemia. In 2 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 approximating the pubis recovered penile supply, avoiding ischemia 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 complication that often requires a complex revision of the epispadias portion of the repair with repeated mobilization of the corporal bodies, in our experience, 5 of the fistulas closed spontaneously as long as a suprapubic tube was left in place to divert 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 unclear, but aggressive tailoring at the bladder neck, whether during 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 osteotomies, are potential factors.5 The obstruction at the urethra or bladder neck presents an immediate danger to the upper urinary tract, leads to urinary tract infections, and is difficult to definitively treat.16 One girl developed this complication, 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 definition of continence as dry intervals of 3 hours or longer, demonstrated 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 experience approaches, but does not match, the results in the previously 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 number of patients (18 of 37) self-reported nearly continuous urinary dribbling with activity and may require ancillary interventions (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 children with stable upper tracts to evaluate continence outcomes as they approach adolescence.17,18 However, continence is a reasonable expectation after PE repair, with published continence 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 location 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.
Short-term surgical missions notoriously have variability in surgical teams and competencies as well as poor patient retention and follow-up. One study following 4100 cleft lip operations 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 published experiences.
Perhaps the most rewarding outcome of this endeavor has been the opportunity to evaluate results and institute outcome improvement initiatives resulting from the accumulated experience gained in treating a large cohort with a rare anomaly. Indeed, as a direct result of an evaluation of the results presented herein, to maximize results without compromising safety, we now perform prospective surgical interventions such as formal bladder neck tapering at time of CPRE to improve continence; bilateral cephalotrigonal reimplants to reduce the prevalence of VUR, carefully assessing penile vascularity 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 rotation of corporal bodies to minimize ventral chordee21; rotational 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 direct result of collaboration.
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 confounding variables may have influenced our results. We also acknowledge 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 continuing the surgical visits, leveraging resources to ensure improved patient retention and evaluation, and minimizing morbidity and mortality that are risks of highly complex reconstructive surgery. Central to this mission remains, of course, the shared goal to enhance the quality of life for the affected individuals.
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 alleviating the global burden of surgical disease. We propose that this collaborative focused on BE and PE with a significant patient retention rate affords an opportunity to rigorously study outcomes achieved after the CPRE over an accelerated interval owing to the high burden of disease at a public hospital in India.
Corresponding Author: Aseem R. Shukla, MD, Division of Urology, 3rd Floor, Wood Bldg, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104 (firstname.lastname@example.org).
Accepted for Publication: December 28, 2017.
Correction: This article was corrected on April 18, 2018, to fix typos in the title and errors in the author degrees, Key Points, and Abstract.
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 collaborative.
Additional Information: Deceased: Richard Grady, MD.
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