Rare exonic CELSR3 variants identified in Bladder Exstrophy Epispadias Complex.

Introduction/background: Bladder exstrophy epispadias complex (BEEC) is a rare congenital anomaly of unknown etiology, although, genetic and environmental factors have been associated with its development. Variants in several genes expressed in the urogenital pathway have been reported as causative for bladder exstrophy in human and murine models. The expansion of next-generation sequencing and molecular genomics has improved our ability to identify the underlying genetic causes of similarly complex diseases and could thus assist with the investigation of the molecular basis of BEEC. Objective: The objective was to identify the presence of rare heterozygous variants in genes previously implicated in bladder exstrophy and correlate them with the presence or absence of bladder regeneration in our study population. Patients and Methods: We present a case series of 12 patients with BEEC who had bladder biopsies performed by pediatric urology during bladder neck reconstruction or bladder augmentation. Cases were classified as "sufficient" or "insufficient" (n = 5 and 7, respectively) based on a bladder volume of greater than or less than 40% of expected bladder size. Control bladder tissue specimens were obtained from patients (n = 6) undergoing biopsies for conditions other than bladder exstrophy. Whole exome sequencing was performed on DNA isolated from the bladder specimens. Based on the hypothesis of de novo mutations, as well as the potential implications of autosomal dominant conditions with incomplete penetrance, each case was evaluated for autosomal dominant variants in a set of genes previously implicated in BEEC. Results: Our review of the literature identified 44 genes that have been implicated in human models of bladder exstrophy. Our whole exome sequencing data analysis identified rare variants in two of these genes among the cases classified as sufficient, and seven variants in five of these genes among the cases classified as insufficient. Conclusion: We identified rare variants in seven previously implicated genes in our BEEC specimens. Additional research is needed to further understand the cellular signaling underlying this potentially genetically heterogeneous embryological condition.

Bladder exstrophy-epispadias complex related litigation: A legal database review.

OBJECTIVE: To review the nature and extent of bladder exstrophy-epispadias related malpractice litigation in the United States. METHODS: Two legal databases (Nexis Uni, WestLaw) were reviewed for state and federal cases using the terms "bladder exstrophy", "cloacal exstrophy", "epispadias", in combination with "medical malpractice", or "negligence", or "medical error", or "complication", or "malpractice", or "tort". Databases were queried from 1948 to 2022 and reviewed for medical and legal details. RESULTS: Our search yielded 16 unique legal cases with 6 fitting established criteria for analysis. Urology and paediatric urologists were named in 50% of cases as were community medical systems. Cause for lawsuit included negligence in surgical performance (50%), primary closure of exstrophy (33%), and post-operative care (50%). Settlement agreement was reached in one case (17%). Outcomes favoured the physician in 60% of trials. Lawsuits alleging negligent surgical performance and/or post-operative care exclusively named urologists with outcomes favouring the surgeon in 66% of cases. The settlement payment (n = 1) was $500,000 and monetary damages (n = 1) equated to $1.3 million. CONCLUSIONS: Malpractice litigation related to BEEC treatment is rare. Trial outcomes favour the medical provider. Cases that resulted in financial liability successfully alleged avoidable negligence resulting in irreversible physical damage. The authors recommend families with BEEC seek board-certified paediatric urologists experienced in treating this complex and/or Bladder Exstrophy Centers of Excellence. Further, we recommend surgeons treating BEEC properly educate patients and families on the severity of this major birth defect including its lifelong implications and need for surgical revisions.

Prevalence of opioid and benzodiazepine use in adult patients with the exstrophy-epispadias complex.

INTRODUCTION: Bladder exstrophy (BE), cloacal exstrophy (CE), and epispadias (E) are variants of the exstrophy-epispadias complex (EEC). These children require opioids and benzodiazepines to achieve pain management and immobilization for a lifetime of surgeries. It is hypothesized that these children would be sensitized to opiates and benzodiazepines as adults. The objective was to identify incidence of opiate and benzodiazepine use in adult EEC patients. METHODS: A US Health network, TriNetX Diamond was queried from 2009 to 2022. Incidence of prescriptions for benzodiazepines and opioids were calculated for adults aged 18-60 years with a diagnosis of BE, CE, or E. RESULTS: A total of 2627 patients were identified: 337 with CE, 1854 patients with BE, and 436 with E. Of these, 55.5% of CE, 56.4% of BE, and 41.1% of E had received any opioid prescription. Non-EEC controls had lower rates of opioids at 0.3%. E had a lower likelihood than BE or CE of receiving opioids (p < 0.0001, p < 0.0001). Benzodiazepines were prescribed in 30.3% of CE, 24.4% of BE, 18.3% of E, and 0.1% of controls. CE had a higher likelihood of benzodiazepines than both BE and E (p = 0.022, p < 0.001, respectively). E group had the lowest likelihood of benzodiazepine prescription (p = 0.007 when compared to BE) and all groups were significantly higher than controls (p < 0.0001 for all comparisons). For BE, females were more likely to be prescribed opioids (p = 0.039) and benzodiazepines (p = 0.027) than males. Sub-analyses revealed BE females had higher rates of surgical procedures (general, cardiac, gastrointestinal, and maternity) and chronic diagnoses (generalized anxiety disorder, major depressive disorder, chronic pain) compared to males with BE. Older age was associated with higher likelihood of opioid or benzodiazepine prescriptions in BE (p < 0.001), CE (p = 0.004), and E (p = 0.002). DISCUSSION: Across the EEC, adult patients with the most severe anomalies of CE were more likely to have received opioids and benzodiazepines. Females with BE were prescribed more opioid and benzodiazepines than males with BE. Mirroring the US population, female sex and increasing age were associated with higher rates of prescriptions, chronic diagnoses, and surgical procedures. Limitations include the lack of granular data and ability to correlate results with childhood surgeries. CONCLUSION: Adult EEC patients have higher rates of opioid and benzodiazepine prescriptions, with a high percentage of co-prescribing when compared to healthy controls. Across the spectrum, those with more severe anomalies, female sex, and increasing age were more likely to have received prescriptions.

Inflammatory Expression Profiles in Bladder Exstrophy Smooth Muscle: Normalization Over Time.

OBJECTIVE: To test the hypothesis that phenotypes in bladder exstrophy result from alterations in detrusor smooth muscle cell (SMC) gene expression. METHODS: We generated primary human bladder smooth muscle cell lines from patients with classic bladder exstrophy (CBE) undergoing newborn closure (n = 6), delayed primary closure (n = 5), augmentation cystoplasty (n = 6), and non-CBE controls (n = 3). Gene expression profiles were then created using RNA sequencing and characterized using gene set enrichment analysis (GSEA). RESULTS: We identified 308 differentially expressed genes in bladder exstrophy SMC when compared to controls, including 223 upregulated and 85 downregulated genes. Bladder exstrophy muscle cell lines from newborn closure and primary delayed closures shared expression changes in 159 genes. GSEA analysis revealed increased expression in the inflammatory response and alteration of genes for genitourinary development in newborn and delayed closure SMC. However, these changes were absent in SMC from older exstrophy patients after closure. CONCLUSION: Bladder exstrophy SMC demonstrate gene expression changes in the inflammatory response and genitourinary development. However, gene expression profiles normalized in exstrophy SMC from older patients after closure, suggesting a normalization of exstrophy SMC over time. Our in vitro findings regarding the normalization of exstrophy SMC gene expression following bladder closure suggest that the development of poor detrusor compliance in bladder exstrophy has a complex multifactorial etiology. Taken together, our findings suggest that alterations in SMC gene expression may explain abnormalities in the exstrophy bladder seen prior to and immediately after closure and suggest that surgical closure may allow exstrophy SMC to normalize over time.

The exstrophy experience: A national survey assessing urinary continence, bladder management, and oncologic outcomes in adults.

INTRODUCTION AND OBJECTIVE: The bladder exstrophy-epispadias complex (BEEC) is a rare spectrum of congenital genitourinary malformations with an incidence of 1:10,000 to 1:50,000. Advances in reconstructive surgical techniques have improved clinical outcomes, but there is a paucity in data about disease sequela in adulthood. This is the largest survey to date in the United States exploring the urinary continence, bladder management, and oncologic outcomes in adults with BEEC. METHODS: Respondents were over the age of 18 with a diagnosis of bladder exstrophy, cloacal exstrophy, or epispadias. They were treated at the authors' institution, included in the Association for the Bladder Exstrophy Community (A-BE-C) mailing list, and/or engaged in A-BE-C social media. A survey was created using uniquely designed questions and questionnaires. Survey responses between May 2020 and July 2020 were processed using Research Electronic Data Capture (REDCap). Quantitative and qualitative statistics were used to analyze the data with significance at p < 0.05. RESULTS: A total of 165 patients completed the survey. The median age was 31.5 years (IQR 25.9-45.9). Many patients considered themselves continent of urine, with a median satisfaction score of 74 (IQR 50-97) on a scale from 0 (consider themselves to be completely incontinent) to 100 (consider themselves to be completely continent). There was less leakage among those with a continent urinary diversion compared to those who void or catheterize per urethra (p = 0.003). Patients with intestinal-urinary tract reconstruction, such as augmentation cystoplasty or neobladder creation, were more likely to perform bladder irrigations (p = 0.03). Patients with continent channels were more likely to report UTI than all other forms of bladder management (89.0% vs. 66.2%, p = 0.003). Three (1.9%) patients were diagnosed with bladder cancer. A small portion of patients (27.2%) were given bladder cancer surveillance recommendations by a physician. DISCUSSION: Most patients achieved a satisfactory level of urinary continence, with the highest continence rates in those with a continent urinary diversion. Those with intestinal-urinary tract reconstruction were more likely to perform bladder irrigations, perhaps to avoid complications from intestinal mucous production. The rates of self-reported UTI and were higher in patients with continent channels, but recurrent UTIs were not affected by the type of genitourinary reconstruction. Bladder cancer exists in this population, highlighting the need for long-term follow-up. CONCLUSION: Most BEEC patients achieve a satisfactory level of urinary continence, with the best outcomes in those with a continent urinary diversion. This population requires long-term follow-up with a transitional urologist to ensure adequate oncologic care.

Postphalloplasty urinary function test: an observational study of novel outcome instrument to capture urinary dysfunction and quality of life after phalloplasty.

Due to growing social acceptance, there has been an increasing number of gender-affirmation surgeries performed in North America. Most research in this patient population focuses on surgical outcomes and advancing techniques. However, little work has been done to study functional outcomes. To better evaluate urinary dysfunction in the postphalloplasty trans men patient population, our group developed a novel patient-reported outcome instrument - the postphalloplasty urinary function test (PP UFT) and protocol to measure postvoid urethral volume (PVUR), and we present our preliminary results. We conducted a cross-sectional pilot study in a cohort of 15 adult trans men who had undergone phalloplasty with urethral lengthening surgery between 2018 and 2021. Patients had stable urinary function via the neophallus at the time of survey. Patients filled out the PP UFT and were asked to record their PVUR as per our protocol. The average PP UFT score was 8.9 out of 40 and the average quality-of-life (QOL) score was 2.6. Postvoid dribbling constituted the major complaint and on average comprised 63.2% of the reported PP UFT score. The average PVUR was 2.2 ml (range: 0.5-5.6 ml). There was a positive correlation between higher PP UFT and worse-reported quality of life (P < 0.01; R2 = 0.4). Current questionnaires accepted in cis-male urology have limitations for accurately capturing urinary dysfunction in this specific patient group. The combination of PP UFT and PVUR measurement offers potential for quantifying urinary function and quality of life in patients who undergo phalloplasty. Future studies will validate these instruments.

Parent Experience of Communication about Children's Surgery: A Qualitative Analysis.

Parent experience is a core component of the quality of pediatric care and an increasingly common focus of quality improvement initiatives. However, the parent experience of communication in the pediatric surgical setting remains unexplored. METHODS: We conducted semi-structured interviews with 20 parents of children undergoing surgery. Interviews were analyzed using directed qualitative content analysis. RESULTS: Content analysis revealed 3 overarching themes. The theme of "provider-parent communication" included interpersonal behaviors and communication-originating skills of the surgeon. Parents valued surgeons incorporating multimodal information-sharing techniques, recognizing children's psychological needs, providing reassurance, engaging in teamwork, and including parents. The theme of "parental emotional experiences" included domains of parent worry, intimidation, offense, self-doubt, mistrust, and strength surrounding their child's surgery. Parents felt simultaneously responsible for their child's welfare and for understanding medical information. The theme of "process improvement" included preparation for surgery, efficiency, managing delays, anesthesia induction, emergence from anesthesia, privacy, and preparation for recovery. CONCLUSIONS: Themes identified through these parental narratives and proposed solutions inform quality improvement efforts related to surgeon communication strategies and facilitate family-centered surgical care for children. Parents often provided solutions after they described concerns, which attests to the utility of parent perspectives.

Osteotomy in the newborn classic bladder exstrophy patient: A comparative study.

INTRODUCTION: Pelvic osteotomy is indicated in classic bladder exstrophy (CBE) patients with a wide pubic diastasis or non-malleable pelvis. While the safety of pelvic osteotomy in delayed and failed closures is established, there remains less clarity on their safety in newborns. The authors herein sought to present their experience with CBE patients who underwent pelvic osteotomy for assistance with bladder closure during both the newborn and delayed time periods. OBJECTIVE: The authors hypothesize that pelvic osteotomy during exstrophy closure may be performed safely in newborns with few perioperative or post-operative negative sequelae. STUDY DESIGN: A prospectively maintained IRB-approved database was reviewed for CBE patients who underwent osteotomy during primary closure. Patient demographics, performing institution (authors' or outside), closure outcome, diastasis width, and post-operative complications were noted. Patient subgroups included newborn and delayed (>28 days of life) closures. Failure was defined as bladder dehiscence, prolapse, outlet obstruction, or vesicocutaneous fistula requiring reoperation. Orthopedic complications included nerve palsies, superficial pin-site infection, and bladder neck erosion by orthopedic hardware. Analyses were performed using a Chi-square test. RESULTS: 286 patients were included: 186 newborn and 100 delayed closures. The authors' institution performed 109 cases (44 newborn and 65 delayed). Within the overall newborn closure cohort, no significant differences were found in outcomes among the osteotomy types with success rates of 80%, 60.8%, and 71.4% in the combined, posterior iliac, and anterior innominate groups, respectively (p = 0.24). In the delayed group, success rates were significantly different with rates of 100%, 72.4%, and 93.8% in the combined, posterior iliac, and anterior innominate groups, respectively (p < 0.001). Febrile urinary tract infection (UTI) was the most common complication at 8% (23/286). Only 1.7% (5/286) of patients had orthopedic complications with 3 patients in the newborn cohort, 2 patients in the delayed cohort, and only one patient requiring reoperation. DISCUSSION: Orthopedic complications are rare in CBE patients who undergo osteotomies regardless of the closure period. No clinically significant difference in orthopedic complication rate was found between newborn and delayed closure periods. CONCLUSIONS: While current trends have moved toward delayed primary closures, there remains a role for osteotomy during exstrophy closure in select newborn patients and can be performed safely with few complications.

Understanding Bias in Surgery: Perceived Cultural Similarity Between Surgeons and Patient Families.

OBJECTIVE: We describe surgeon and parent perceptions of similarity toward each other and evaluate differences in the perceptions of similarity by race. STUDY DESIGN: Observational cohort analysis. SETTING: Three outpatient sites. METHODS: Following consultations for children undergoing evaluation for 1 of 3 surgical procedures (tonsillectomy, hernia repair, circumcision), surgeons and parents rated their perception of cultural similarity toward each other on a 6-point Likert scale. Surgeon evaluation of 9 parent characteristics was measured with 7-point Likert scales. Regression analyses were performed to identify predictors of greater surgeon-perceived similarity and to assess associations of perceived similarity with evaluation of parent characteristics. RESULTS: Most parents were women (n = 38, 84%), whereas surgeons were primarily men (n = 7, 54%). Of 45 parents, 23 (51%) were non-White, whereas only 4 of 13 clinicians (31%) were non-White. Mean perceived similarity score was 21.7 for parents (range, 10-24) and 18.2 for surgeons (range, 10-24). There was no difference in parent-perceived similarity based on race (White vs non-White parents, mean [SD] = 22.3 [3.4] vs 21.1 [3.0]; P = .26). Surgeons perceived greater similarity with White parents (odds ratio = 4.78; 95% CI, 1.02-22.54; P = .04) and parents with higher income (odds ratio = 11.84; 95% CI, 1.32-106.04; P = .03). Greater perceived similarity by the surgeons was associated with more positive assessments of parent personality characteristics. CONCLUSION: Surgeons perceived similarity more commonly with White parents, while parents' perception of similarity to surgeons was uniform regardless of parent race. Elucidating biases of surgeons may help to tailor interventions promoting culturally competent, equitable communication and decision making for elective surgery.

Antireflux Surgery at National Surgical Quality Improvement Program-Pediatric Hospitals.

PURPOSE: This study aims to examine contemporary practice patterns and compare short-term outcomes for vesicoureteral reflux procedures (ureteral reimplant/endoscopic injection) using National Surgical Quality Improvement Program-Pediatric data. MATERIALS AND METHODS: Procedure-specific variables for antireflux surgery were developed to capture data not typically collected in National Surgical Quality Improvement Program-Pediatric (eg vesicoureteral reflux grade, urine cultures, 31-60-day followup). Descriptive statistics were performed, and logistic regression assessed associations between patient/procedural factors and outcomes (urinary tract infection, readmissions, unplanned procedures). RESULTS: In total, 2,842 patients (median age 4 years; 76% female; 68% open reimplant, 6% minimally invasive reimplant, 25% endoscopic injection) had procedure-specific variables collected from July 2016 through June 2018. Among 88 hospitals, a median of 24.5 procedures/study period were performed (range 1-148); 95% performed ≥1 open reimplant, 30% ≥1 minimally invasive reimplant, and 70% ≥1 endoscopic injection, with variability by hospital. Two-thirds of patients had urine cultures sent preoperatively, and 76% were discharged on antibiotics. Outcomes at 30 days included emergency department visits (10%), readmissions (4%), urinary tract infections (3%), and unplanned procedures (2%). Over half of patients (55%) had optional 31-60-day followup, with additional outcomes (particularly urinary tract infections) noted. Patients undergoing reimplant were younger, had higher reflux grades, and more postoperative occurrences than patients undergoing endoscopic injections. CONCLUSIONS: Contemporary data indicate that open reimplant is still the most common antireflux procedure, but procedure distribution varies by hospital. Emergency department visits are common, but unplanned procedures are rare, particularly for endoscopic injection. These data provide basis for comparing short-term complications and developing standardized perioperative pathways for antireflux surgery.

Delaying primary closure of classic bladder exstrophy: When is it too late?

INTRODUCTION: With current trends towards delaying the closure of classic bladder exstrophy (CBE), bladder growth rate or ultimate capacity may be impacted. OBJECTIVE: To examine consecutive bladder capacities in CBE patients who had primary closures at differing ages and determine whether there is an optimal age for closure, with reference to bladder capacity. STUDY DESIGN: A retrospective review was performed using an institutional database. INCLUSION CRITERIA: CBE, successful neonatal (i.e. ≤28 days old) or delayed (i.e. >28 days old) primary closure, at least three consecutive bladder capacities or two measures taken 18 months apart, and first bladder capacity measured ≥3 months after closure. Only capacities prior to continence surgery and before 14 years of age were considered. Two cohorts were created: neonatal and delayed closure. To account for repeated measurements per patient, a linear mixed model evaluated effects of age and length of delay on bladder capacity based on closure cohort. Individuals in the delayed closure group were further stratified into quartiles to assess for detriment to the bladder based on length of delay. RESULTS: The cohort included 128 neonatal and 38 delayed patients. Median age at closure for the delayed group was 193 days (IQR 128-299). Based on univariate analysis, for the first three capacity measurements, the delayed group had significantly lower capacities despite having a similar median age when the measurements were taken. Linear mixed effects model showed significantly decreased total bladder capacity in delayed closure compared to neonates. The 2nd and 4th quartile groups had the most significant decreases in capacity. DISCUSSION: Time points for the most significant decline appear after the 2nd and 4th quartiles, representing 4-6 months and beyond 9 months, respectively. From this, the authors theorize that the appropriate time to close an exstrophy patient is as early as possible (1st quartile), or, if a delay is needed for growth of a bladder template, then between 6 and 9 months (3rd quartile). There may be a detriment to growth rate, however, statistical power may be lacking to discern this. Study limitations include the single-centered, retrospective design. However, results described here fill an important deficit in the knowledge of managing CBE. CONCLUSIONS: All patients in the delayed bladder closure group demonstrated a decline in bladder capacity compared to the control neonatal closure group, with significant differences in the 2nd and 4th quartiles. Thus, closing the bladder prior to nine months of age is recommended.

Practice patterns in classic bladder exstrophy: A global perspective.

INTRODUCTION: While evaluation and management options for classic bladder exstrophy (CBE) patients are numerous and varied, little is known regarding the relative utilization of these different methods throughout the world. A large group of exstrophy surgeons practicing globally was surveyed, seeking to document their methods of care. METHODS: A list of international exstrophy surgeons' email addresses was compiled using professional contacts and referral networking. An online survey was sent to each email address. Surgeons who had not performed a CBE closure within the previous 5 years were excluded. Survey questions queried the respondents' surgical practice type, years since training, and their preferred methods of preoperative evaluation, operative management, and postoperative management. Survey invitations were sent out starting in December 2014 and responses were collected for approximately 6 months. RESULTS: A total of 1152 valid email addresses were invited, resulting in 293 respondents (25%) from 39 countries and every American Urological Association (AUA) section. Seventy-six were excluded, leaving 217 respondents (Table). Respondents reported a median of 17 years since finishing their surgical training (IQR 8-25 years). Practice types included pediatric urology (n = 209), general urology (n = 9), pediatric surgery (n = 59), and other practice makeup (n = 3). On subgroup analyses, there were no significant regional practice differences, with the exception of complete primary repair of exstrophy (CPRE) and oral opioid prescribing being significantly higher in North America compared to other regions. DISCUSSION: Findings indicate that there may be diversity in CBE practice patterns globally. While most responding surgeons from regions outside of North America indicated modern staged repair of exstrophy (MSRE) as their preferred closure technique, a relatively equal distribution of respondents from North America selected CPRE and MSRE. A majority of North American surgeons chose performing osteotomies for both newborn and delayed closures, while an appreciable number of respondents from other regions selected never using osteotomies in their closures. Limitations to this study include a low survey response rate, particularly from surgeons outside of the United States, which may have significantly impacted the ability to draw meaningful global comparisons. CONCLUSIONS: Global variation among practices of surgeons performing CBE closures may exist. The wide range of methods demonstrated by this survey suggests the need for more conclusive comparative studies to elucidate whether an optimal standard exists. Local social factors, access to surgical expertise and transportation to referral centers, and finances play a role in what constitutes the best operative approach.

Exploration of Practice Patterns in Exstrophy Closures: A Comparison Between Surgical Specialties Using a National and Institutional Database.

OBJECTIVE: To compare the surgical subspecialties performing bladder exstrophy closures and characterize their practice patterns using both a national and institutional database. METHODS: The National Surgical Quality Improvement Program Pediatric (NSQIPP) database was reviewed for all bladder exstrophy closures performed from 2012 to 2017. A single institutional exstrophy-epispadias complex database of 1337 patients was reviewed for patients with a bladder closure at a referring institution from 1975 to 2018. Patients with cloacal exstrophy were excluded. The subspecialties of the surgeons performing the closures were identified. Practice patterns such as the use of a pelvic osteotomy and postoperative immobilization, and perioperative outcomes were compared for each subspecialty group. RESULTS: A total of 84 bladder exstrophy patients from NSQIPP and 263 from the author's institutional database met the inclusion criteria. From NSQIPP, 88% of closures were performed by pediatric urologists while 12% were done by other subspecialists. From the institutional database, 75% of referred bladder exstrophy closures were done by a pediatric urologist, and 25% by other services. Gender, race, operation time, length of stay, and postoperative complications were not significantly different between the groups. In one database, pediatric surgeons performed closures earlier, and in another database, pediatric urologists had greater utilization of osteotomy with different immobilization techniques. Pediatric urologists had a higher success rate. CONCLUSION: Pediatric urologists performed the most bladder exstrophy closures in both databases; they operated on more delayed closures with a greater use of adjunctive procedures and a higher success rate. Differences in surgical training may contribute to the differences in practice patterns.

The failed bladder closure in cloacal exstrophy: Management and outcomes.

PURPOSE: Cloacal exstrophy (CE) is the most severe presentation of the Exstrophy-Epispadias Complex (EEC) and is associated with an omphalocele, making the bladder and abdominal wall closure difficult. If the bladder closure fails, a secondary closure is necessary. The objective of this study is to identify patient or surgical factors associated with a successful secondary closure. METHODS: The institution's EEC database was reviewed for CE patients between 1975 and 2015. Inclusion criteria included a failed primary bladder closure with a secondary closure. Patient demographics, surgical factors and outcomes of the secondary bladder closure were reviewed. RESULTS: Twenty-four patients met inclusion criteria. 8/8 patients had a successful two-staged closure at the author's institution (100%); 2/16 patients had a successful closure at an outside institution (12.5%). Older median age at secondary closure was associated with outcome, p = 0.045. Pelvic osteotomy was associated with successful secondary closure, p = 0.013. Using Buck's immobilization with external fixation was associated with a higher proportion of successful secondary closures compared to Spica cast, p = 0.012. CONCLUSION: Successful reclosure in CE patients is associated with the use of osteotomy as well as Buck's immobilization with external fixation. While successful reclosure can be achieved, it is often at the cost of multiple procedures and, therefore, all efforts should be expended to achieve a successful primary closure. TYPE OF STUDY: Prognostic. LEVEL OF EVIDENCE: III.

Novel Observations of Female Genital Anatomy in Classic Bladder Exstrophy Using 3-Dimensional Magnetic Resonance Imaging Reconstruction.

PURPOSE: Understanding the distinct female anatomy in classic bladder exstrophy is crucial for optimal reconstructive and functional outcomes. We present novel quantitative anatomical data in females with classic bladder exstrophy before primary closure. MATERIALS AND METHODS: 3-Dimensional reconstruction was performed in patients undergoing pelvic magnetic resonance imaging, and pelvic anatomy was characterized, including measurements of the vagina, cervix and erectile bodies. RESULTS: We examined magnetic resonance imaging of 5 females (mean age 5.5 months) with classic bladder exstrophy and 4 age matched controls (mean age 5.8 months). Mean distance between the anal verge and vaginal introitus was greater in patients with classic bladder exstrophy (2.43 cm) than in controls (1.62 cm). Mean total vaginal length in patients with classic bladder exstrophy was half that of controls (1.64 cm vs 3.39 cm). All 4 controls had posterior facing cervical ora, while 4 of 5 females with exstrophy had anterior facing cervical ora located in the anterior vaginal wall. Lateral deviation of the cervical ora was also seen in all 5 patients with classic bladder exstrophy but in only 1 control. Clitoral body length was comparable in both groups (26.2 mm and 28.0 mm). However, the anterior cavernosa-to-posterior (pelvic rami associated) cavernosa ratio was much greater in patients with classic bladder exstrophy (6.4) compared to controls (2.5). CONCLUSIONS: This study uncovers the uniquely novel finding that contrary to their male counterparts, females with classic bladder exstrophy have the majority of the clitoral body anterior to the pelvic attachment. This discovery has surgical and embryological implications.

Cystectomy in the Pediatric Exstrophy Population: Indications and Outcomes.

OBJECTIVE: To explore the long-term outcomes and indications for cystectomy in patients with bladder exstrophy. Although rare, cystectomy is the final surgical alternative to bladder repair among these patients with a poor quality bladder template. METHODS: A prospectively maintained database of 1298 patients with exstrophy-epispadias complex was reviewed for patients who underwent cystectomy between 1970 and 2015 at the authors' institution. Demographic data, indication for cystectomy, surgical history, postoperative outcomes, and continence status were collected. RESULTS: Eighteen (6 male; 12 female) patients with exstrophy (15 classic bladder exstrophy; 2 bladder exstrophy variants; 1 cloacal exstrophy) underwent cystectomy at a median age of 3.8 years. Six patients (33.3%) underwent primary cystectomy without attempted bladder closure. Eight patients (44.4%) had a history of failed primary closure with loss of capacity or inadequate growth after closure. Four patients (22.2%) had successful primary closure but underwent cystectomy secondary to poor bladder compliance with declining renal function or poor bladder growth or quality. Urinary diversion included 6 cutaneous ureterostomies, 4 bowel conduits (1 ileal; 3 colon), 6 continent urinary diversions with ileosigmoid reservoir, and 1 ureterosigmoidostomy. Of 8 patients who underwent a continence procedure, all were dry at a median of 25.3 months after cystectomy. CONCLUSION: Cystectomy was most commonly indicated in intrinsically diseased bladder templates that remained too small despite permitting time for interval growth. These bladders often were of poor quality and compliance and did not reduce into the pelvis on examination. It was, however, possible to achieve urinary continence in these patients with cystectomy and urinary diversion.

The Surgical Management of Bladder Polyps in the Setting of Exstrophy Epispadias Complex.

OBJECTIVE: To investigate the surgical course for treating bladder polyps in patients with exstrophy epispadias complex (EEC). EEC bladder polyps are unique pathologic entities, with a distinct difference between polyps discovered at birth and polyps developed after failed exstrophy closure. METHODS: A prospectively maintained database of 1300 patients with EEC was reviewed for bladder exstrophy patients with bladder polyps. The following data were obtained: patient demographics, polyp type, past medical and surgical history, and continence outcomes. Polyps were categorized as (1) primary, bladder polyps at birth or during neonatal period; and (2) secondary, bladder polyps following a failed exstrophy closure. RESULTS: Of 1300 EEC patients, 43 patients with polyps met the inclusion criteria. All closures for primary polyp patients were successful, and continence outcomes remained similar in early and delayed closures (P = .689). Secondary polyp patients were more likely to require augmentation to increase bladder capacity (P = .033). Bladder neck reconstruction (n = 8) was successful in 83.0% of patients with primary polyps, and none were successful for those with secondary polyps (P = .035). CONCLUSION: Delaying primary bladder closure for patients with small polypoid bladder templates did not affect closure or continence outcomes. However, primary and secondary polyps may require different surgical interventions. Bladder neck reconstruction was markedly less successful in secondary polyp patients, and secondary polyp patients were more likely to need augmentation to increase bladder capacity. This study emphasizes the importance of a successful primary closure and suggests that secondary polyps are an indicator of decreasing potential for bladder growth.