Classic Bladder Exstrophy Patients Research Articles

Modern Management of the Failed Bladder Exstrophy Closure: A 50-yr Experience

BackgroundA failed closure of classic bladder exstrophy (CBE) has a negative long-term impact on the patient and the health care system. ObjectiveTo investigate the outcomes of CBE patients with failed primary bladder closure. Design, setting, and participantsA database of 1317 exstrophy-epispadias complex patients was retrospectively reviewed for CBE patients with failed primary bladder closure from 1965 to 2017 with subsequent repeat closure. InterventionRepeat bladder exstrophy closure and subsequent continence procedure. Outcome measurements and statistical analysisFailed exstrophy closures are defined as occurrence of bladder prolapse, dehiscence, vesicocutaneous fistula, outlet obstruction, or combination of these factors. Successful repeat closures are defined as closures that require no further operative intervention as a consequence of these factors. Kaplan-Meier to determine time to successful repeat closure and receiver operator characteristic curve to determine the optimal time for secondary closure were determined. Results and limitationsIn total, 170 CBE patients had at least one repeat closure following a failed primary closure (115 male/55 female). With continued closure attempts, 166/170 (97.6%) patients were successfully closed. The median time to successful closure from birth was 12.9 mo (95% confidence interval: 11.7–15.7). Furthermore, 52/153 (34%) patients had more than one osteotomy. Of 215 total osteotomies, 50 (29.4%) were performed during the 170 failed primary closures, 128 (75.3%) during the 170second closures, and 27 (64.3%) during the 42 third closures. Of 96 patients with available continence data, 74 (77.1%) achieved urinary continence. ConclusionsA successful repeat closure is possible, especially when used in conjunction with a pelvic osteotomy. Continent urinary diversion yielded the highest continence rate in this cohort. Patient summaryWe looked at outcomes of classic bladder exstrophy closure in a large population. Successful repeat closure is possible in the majority of cases when used with pelvic osteotomy. A majority of patients achieved urinary continence using a continent diversion.

Predictors and outcomes of perioperative blood transfusions in classic bladder exstrophy repair: A single institution study

Primary bladder closure of classic bladder exstrophy (CBE) is a major operation that occasionally requires intraoperative or postoperative (within 72h) blood transfusions. This study reported perioperative transfusion rates, risk factors for transfusion, and outcomes from a high-volume exstrophy center in primary bladder closure of CBE patients. A prospectively maintained, institutional exstrophy-epispadias complex database of 1305 patients was reviewed for primary CBE closures performed at the authors' institution (Johns Hopkins Hospital) between 1993 and 2017. Patient and surgical factors were analyzed to determine transfusion rates, risk factors for transfusions, and outcomes. Patients were subdivided into two groups based upon the time of closure: neonatal and delayed closure. A total of 116 patients had a primary bladder closure during 1993-2017. Seventy-three patients were closed in the neonatal period, and 43 were delayed closures. In total, 64 (55%) patients received perioperative transfusions. No transfusion reactions were observed. Twenty-five transfusions were in the neonatal closure group, yielding a transfusion rate of 34%. In comparison, 39 patients were transfused in the delayed closure group, giving a transfusion rate of 91%. Pelvic osteotomy, delayed bladder closure, higher estimated blood loss (EBL), larger pubic diastasis, and longer operative time were all associated with blood transfusion. In multivariable logistic regression, pelvic osteotomy (OR 5.4; 95% CI 1.3-22.8; P<0.001), higher EBL-to-weight ratio (OR 1.3; 95% CI 1.1-1.6; P=0.029), and more recent years of primary closure (OR 1.1; 95% CI 1.0-1.2; P=0.018) remained independent predictors of receiving a transfusion (Summary Table). No adverse transfusion reactions or complications were observed. This was the first study from a single high-volume exstrophy center to explore factors that contribute to perioperative blood transfusions. Pelvic osteotomy as a risk factor was unsurprising, as the osteotomy may bleed both during and immediately after closure. However, it is important to use osteotomy for successful closure, despite the increased transfusion risk. The risks accompanying contemporary transfusions are minimal and osteotomies are imperative for successful bladder closure. More than half of CBE patients undergoing primary closure at a single institution received perioperative blood transfusions. While there was an association between transfusions and osteotomy, delayed primary closure, larger diastasis, increased operative time, and increased length of stay, only the use of pelvic osteotomy, higher EBL-to-weight ratio, and recent year of closure independently increased the odds of receiving a transfusion on multivariate analysis.

The inadequate bladder template: Its effect on outcomes in classic bladder exstrophy

Newborns with classic bladder exstrophy (CBE) may present with a bladder template that is inadequate for closure in the neonatal period (figure). In these cases, a delayed primary closure (DPC) is conducted to permit growth of the bladder template. This study reports the surgical and long-term urinary continence outcomes of poor template CBE patients undergoing DPC and compares them to patients who underwent DPC for reasons unrelated to bladder quality (i.e., prematurity, comorbidities, or a late referral). An institutionally approved, prospectively maintained database of 1330 exstrophy-epispadias complex patients was reviewed for CBE patients who underwent DPC at the authors' institution. A bladder template was considered inadequate for neonatal closure if found to be inelastic, <3cm in diameter, and/or covered in hamartomatous polyps. In total, 63 patients (53 male and 10 female) undergoing DPC were identified. Of these, 36 had poor bladder templates (group 1). The remaining 27 patients (group 2) had adequate templates and their bladder closure was delayed for reasons unrelated to bladder quality. At the time of DPC, those in group 1 were relatively than those in group 2 (median of 229 vs. 128 days, p=0.094). All 36 group 1 patients and 26 (96%) group 2 patients underwent pelvic osteotomy during DPC (p=0.429). All patients in this study had a successful primary closure. There was little difference in longitudinal bladder capacities between group 1 and group 2 (p=0.518). Also, there was minimal difference in the median number of continence procedures between groups, with both groups having 1 (IQR 1-1) continence procedure (p=0.880). Eight patients in group 1, and three patients in group 2 underwent a bladder neck transection with urinary diversion. Of the 13 and 16 patients who have undergone a continence procedure in group 1 and 2, respectively, 11 (84.6%) and 13 (81.3%) are continent of urine. The age of first continence procedure was different between groups 1 and 2 at 8.0 years (5.8-9.9 years) and 4.8 (3.5-6.0 years), respectively p=0.009. The majority of patients in group 1 established continence at a relatively later age when compared to those in group 2, at 11.4 (8.0-14.8) years and 7.9 (2.6-13.2) years of age respectively p=0.087. In the authors' view, neonatal bladder closure is ideal for CBE patients as it minimizes potential damage to exposed bladder mucosa. However, prior studies indicate that the rate of bladder growth for patients undergoing a delayed primary closure does not differ from patients with a neonatal closure. Results from this study show continued evidence that patients with poor templates who undergo delayed closure have excellent primary closure outcomes, which is critical for further management. Furthermore, this study shows that an inadequate bladder does not affect DPC outcomes or the continence outcomes in DPC patients. However, the inadequate template does affect the type of continence procedure available to a DPC patient, the age of first continence procedure, and the age of continence. DPC of the exstrophic bladder has a high rate of success when pelvic osteotomy is utilized as an adjunct. Patients having a DPC for reasons of an inadequate bladder template have comparable rates of bladder growth when compared to DPC of an adequate bladder template. The inadequate bladder template affects the type of continence procedure, with the majority of patients requiring urinary diversion for continence. Patients with an inadequate bladder template have a later age of first continence procedure and a relatively later age of continence, because of an inherently smaller bladder template at birth. The inadequate bladder template patients require a longer period of surveillance to access bladder growth and capacity in preparation of a continence procedure. Furthermore, as the majority of inadequate bladder template patients require a catheterizable channel for continence, the age of continence is also likely influenced by the patient's preparation as they transition from volitional voiding to catheterization.

MP25-02 PENILE DISASSEMBLY IN EXSTROPHY: TIME TO REEVALUATE?

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: External Genitalia Reconstruction and Urotrauma (including transgender surgery) II1 Apr 2018MP25-02 PENILE DISASSEMBLY IN EXSTROPHY: TIME TO REEVALUATE? Matthew Kasprenski, Mahir Maruf, John Jayman, Karl Benz, Jason Michaud, Emily Dunn, and John Gearhart Matthew KasprenskiMatthew Kasprenski More articles by this author , Mahir MarufMahir Maruf More articles by this author , John JaymanJohn Jayman More articles by this author , Karl BenzKarl Benz More articles by this author , Jason MichaudJason Michaud More articles by this author , Emily DunnEmily Dunn More articles by this author , and John GearhartJohn Gearhart More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.839AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Epispadias repair, using the complete penile disassembly technique, is frequently combined with primary bladder closure in patients with classic bladder exstrophy (CBE). Yet, penile disassembly has been posited as a risk for penile injury by ischemic mechanisms. Herein, the authors present all CBE cases referred to their institution where primary closure with penile disassembly epispadias repair was complicated by penile injury. METHODS A prospectively-maintained institutional database of 1311 exstrophy-epispadias complex patients was reviewed for complete primary repair of CBE cases referred to the authors' institution, and those with injury to the penis were identified. The location, extent of injury, and subsequent management is reported. Triplanar magnetic resonance imaging (MRI) of the pelvis with volumetric analysis was used for penile compartment quantification. RESULTS Of the 170 CBE patients referred after a prior complete primary repair, 22 (13%) were identified with penile loss. A majority (82%) were closed in the neonatal period, and 55% had a pelvic osteotomy. Eight patients (38%) had a failed primary closure. Median follow-up time was 10 years (range 3-21). Penile injury was often unilateral (82%), and involved the glans and/or corpora cavernosa. MRI of the pelvis confirmed anterior corporal deficiency that resulted from primary closure. Three patients were successfully managed with myocutaneous neophalloplasty between the ages of 15 and 16 years old. CONCLUSIONS As a part of the primary bladder closure, penile disassembly for epispadias repair may lead to penile ischemia. In addition to reconstructive planning, MRI may be used to quantify penile injury. CBE patients with penile injury can be managed with myocutaneous phalloplasty. Because of the soft tissue loss with complete penile disassembly, it may be time to reevaluate the application of this technique in the reconstruction of bladder exstrophy. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e326 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Matthew Kasprenski More articles by this author Mahir Maruf More articles by this author John Jayman More articles by this author Karl Benz More articles by this author Jason Michaud More articles by this author Emily Dunn More articles by this author John Gearhart More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

How to close classic bladder exstrophy: Are subspecialty training and technique important?

Successful primary closure is one of the main factors for achieving continence in a classic bladder exstrophy (CBE) patient. Even with contemporary management, patients still have failed primary closures. We sought to understand the role of training, surgical technique, and their impacts on outcomes of CBE closure. A retrospective cohort study from the largest single-institution database of primary and re-closure CBE patients in the world was performed. Failed closure was defined as developing bladder outlet obstruction, wound dehiscence, bladder prolapse, or any need for a re-closure operation. Patient demographics and surgical factors were abstracted and analyzed. Multivariable analysis was performed to test for associations with successful exstrophy closure. Data from 722 patients were analyzed. On bivariate analysis, successful closure was associated with gestational age at presentation, time of closure, location of closure, credential of surgeon performing the closure, closure type, concomitant osteotomy, and type of immobilization. Multivariable analysis, adjusting for patient comorbidity and location of closure, demonstrated increased odds of failure for closure by pediatric surgeon compared with pediatric urologist (OR 4.32, 95% CI 1.98-9.43; p=0.0002), closure by unknown credentialed surgeon (OR 1.86, 95% CI 1.15-2.99; p=0.011), Complete Primary Repair of Exstrophy (CPRE) closure compared with Modern Staged Repair of Exstrophy (OR 2.05, 95% CI 1.29-2.99; p=0.0024), and unknown closure type (OR 4.81, 95% CI 2.94-7.86; p<0.0001) (Table). Many factors associated with failure on bivariate analysis can be explained by these patients presenting to a center of excellence or the selection bias of this cohort stemming from a single center database that have been previously published. However, the finding on adjusted multivariable logistic regression analysis that closure by a pediatric surgeon is associated with higher odds of failure is novel. The additional finding that CPRE closure is associated with failure is most likely secondary to these patients being referred to our institution after having been closed with CPRE which falsely increases its impact on closure failure. Nevertheless, as a center with a large exstrophy volume, this study draws from a cohort that is larger than any other. Classic bladder exstrophy closure should be performed at a center with pediatric urologists to ensure the best chance of a successful primary closure.

Bladder exstrophy closure in the newborn period with external pelvic fixation performed without osteotomy: A preliminary report

Successful primary bladder closure is the most crucial element for urinary continence in patients with classic bladder exstrophy (CBE). In the newborn period, bladder closure can be performed in the first 48h without pelvic osteotomy or external fixation, but requires postoperative lower extremity immobilization (i.e., spica cast, Bryant's or Buck's traction). To present a novel surgical approach for primary bladder closure for CBE using two-pin external fixation without pelvic osteotomy, and without postoperative lower extremity immobilization. A retrospective chart review of patients with CBE was performed at the current institution from 2000 to 2016, including all primary bladder closures with external fixation and without osteotomy or lower extremity immobilization. Patients were discharged with the external fixator in place, which was later removed in clinic. Baseline clinical and demographic variables, and follow-up data were recorded. Thirteen patients were analyzed; eight (61.5%) were male. Pre-operative intersymphysial distance was 3.68±1.0cm (2.0-5.0). Mean follow-up was 56.8±40.3 months (10-131). One patient had a partial bladder neck dehiscence, due to pin displacement on postoperative day 1: he had the lowest gestational age of 34 weeks (Summary table). This approach used external fixation to bring the pubic bones together intra-operatively, and to decrease the tension in closing the pelvic ring and abdominal wall without osteotomy. External fixation with osteotomy and long-term immobilization, or using a spica cast without osteotomy offered the added advantage of improved wound care, due to lack of lower limb immobilization, less patient discomfort, and facilitation of mother/caregiver and newborn bonding. The two-pin external fixator without osteotomy as an adjunct to primary bladder closure in CBE patients was technically feasible. At the current institution this approach had an equivalent success rate to previous reports in the literature for primary bladder closure, decreased the length of hospital stay, and precluded the need for lower extremity immobilization. Early data for bladder capacity were encouraging.

Role of the LF-SINE-Derived Distal ISL1 Enhancer in Patients with Classic Bladder Exstrophy.

A genome-wide association study and meta-analysis identified ISL1 as the first genome-wide significant susceptibility gene for classic bladder exstrophy (CBE). A short interspersed repetitive element (SINE), first detected in lobe-finned fishes (LF-SINE), was shown to drive Isl1 expression in embryonic mouse genital eminence. Hence, we assumed this enhancer a conclusive target for mutations associated with CBE formation and analyzed a cohort of 200 CBE patients. Although we identified two enhancer variants in five CBE patients, their clinical significance seems unlikely, implying that sequence variants in the ISL1 LF-SINE enhancer are not frequently associated with CBE.

ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development

Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 × 10−08). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 × 10−19. Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.

Incidence of Hip Dysplasia Associated With Bladder Exstrophy.

Exstrophy of the bladder is a rare congenital defect seen in 2.15 children out of every 100,000 live births, with the most severe variant, cloacal exstrophy (CE), only occurring in 1 in 200,000. Developmental dysplasia of the hip (DDH) describes a spectrum of disease ranging from mild hip instability to frank dislocation. Underlying malformations, such as myelomeningocele and arthrogryposis, are often associated with the most severe variant of hip dysplasia, teratologic hip dislocation. The varying degrees of severity in DDH have been encountered in classic bladder exstrophy (CBE) patients, but the exact incidence is unknown. We sought to determine the incidence of DDH in CBE and CE patients. We performed a retrospective review of all children with CBE or CE presenting to a single pediatric center between 1994 and 2014. Each chart was reviewed for correct diagnosis of CBE or CE, patient age and demographics, associated medical conditions, pertinent surgeries performed, and the age at operation. Patient imaging was reviewed to determine whether bilateral hip imaging was available. In a 20-year retrospective review, we identified 66 patients who were diagnosed with either CBE or CE and had available hip imaging (38 males and 28 females). Of these, 11 patients were found to have radiographic evidence of DDH, for an incidence of 16.7% (11/66). Five of these patients had CE, whereas 6 presented with CBE. The first radiographic evidence of DDH was noted at a mean age of 5.75 years (range, birth to 22 y). We advocate the use of routine hip screening ultrasound in all infants born with either CBE or CE. Early identification of DDH in these patients may allow additional treatment options to coincide with frequently used osteotomy and orthopaedic interventions. Level III-retrospective study.

MP81-12 LONG-TERM SEXUAL HEALTH OUTCOMES IN MEN WITH CLASSIC BLADDER EXSTROPHY

You have accessJournal of UrologySexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II1 Apr 2016MP81-12 LONG-TERM SEXUAL HEALTH OUTCOMES IN MEN WITH CLASSIC BLADDER EXSTROPHY Ross Everett, Timothy Baumgartner, Kathy Lue, Ezekiel Young, Sunil Reddy, Uzoma Anele, Nilay Gandhi, Cameron Alexander, Heather Di Carlo, and John Gearhart Ross EverettRoss Everett More articles by this author , Timothy BaumgartnerTimothy Baumgartner More articles by this author , Kathy LueKathy Lue More articles by this author , Ezekiel YoungEzekiel Young More articles by this author , Sunil ReddySunil Reddy More articles by this author , Uzoma AneleUzoma Anele More articles by this author , Nilay GandhiNilay Gandhi More articles by this author , Cameron AlexanderCameron Alexander More articles by this author , Heather Di CarloHeather Di Carlo More articles by this author , and John GearhartJohn Gearhart More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2065AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Long-term sexual outcomes in men born with classic bladder exstrophy (CBE) is an area of growing interest. With the transition from adolescence to adulthood, relationships and sexual performance have increasing importance. Currently, there is a paucity of data regarding the relationship status and sexual well-being of CBE patients in adulthood. The authors′ aim is to further quantify these quality of life components to allow for enhanced psychosocial support and medical care in adulthood. METHODS A prospectively-maintained institutional database comprised of 407 patients with CBE was utilized. Male patients 18 years or older were included. The Sexual Health Inventory for Men (SHIM) and the Penile Perception Score (PPS) questionnaire were utilized as well as study specific questions on health, relationship, and fertility status. Patients were contacted via telephone and were given the option to complete the survey via telephone, internet, or mailed paper. RESULTS A total of 215 men were identified, of which 72 (33.5%) completed the questionnaire. The mean age of the participants was 32.3 years, and 64% were in a relationship. 83% of the respondents had been sexually active in their lifetime, with 94% reporting a moderate to very high sexual desire. 71% had high to very high confidence in their ability to obtain and maintain an erection, and 73% were confident they would have an erection sufficient for penetration a majority of time. In light of their strong libido and erectile function, only 57 % were moderately to very satisfied with their sex life. The average SHIM score was 19.5. The PPS revealed all aspects of assessment scored an average between the dissatisfied and satisfied range on the four point Likert scale, except for penile length which was between very dissatisfied and dissatisfied with a score of 0.82. Fertility was identified as somewhat to very important to 72% of the respondents. Despite this reported importance, only 26% had attempted to obtain pregnancy with their partner. This may be related to the concern of 47% of the men that they may be infertile. 15% were successful in achieving pregnancy with their partner, while 28% report a confirmed fertility problem. 25% of the responders report having a semen analysis or post-ejaculatory urinalysis. Of the samples collected, only 2 individuals reported azoospermia. CONCLUSIONS CBE patients have many of the same sexual and relationship successes and concerns as the general population. This is invaluable data to provide to both the parents of boys with CBE, as it is to the patients themselves as they transition to adulthood. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1057-e1058 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Ross Everett More articles by this author Timothy Baumgartner More articles by this author Kathy Lue More articles by this author Ezekiel Young More articles by this author Sunil Reddy More articles by this author Uzoma Anele More articles by this author Nilay Gandhi More articles by this author Cameron Alexander More articles by this author Heather Di Carlo More articles by this author John Gearhart More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The cost of failure: The economic impact of failed primary closure in classic bladder exstrophy

PurposeFailure of primary closure in classic bladder exstrophy (CBE) is a significant cause of morbidity, and yet its relative economic impact has not been well characterized. The authors aim to determine whether CBE patients who underwent failed primary closure incur greater economic burden in the year following their successful closure than those patients who underwent a successful primary closure. Materials and MethodsAfter institutional review board approval CBE patients who were successfully closed between 1993 and 2013 were identified in an institutional exstrophy–epispadias database. Patients who were never closed at the study institution and those who had no documented successful closure were excluded. Inpatient hospital charges, hospital costs, and professional fees were collected for the year following successful closure. Results162 patients met the inclusion and exclusion criteria and accounted for 312 inpatient admissions in the year following and including their respective successful bladder closures. 62 of the patients failed their primary closure and the remaining 100 succeeded. Adjusting for covariates, patients who underwent successful primary closure experienced a reduction in inpatient hospital charges of $8497, hospital costs of $9046 and professional fees of $11,180 in the year following their successful closure compared to those patients who failed their primary closure. ConclusionApart from the self-evident financial advantages of a successful primary closure, namely the avoidance of reclosure, there appears to be a lasting negative financial impact of failed primary closure even after these patients undergo successful reclosure at the study institution.

Newborn exstrophy closure without osteotomy: Is there a role?

Recent articles document successful classic bladder exstrophy (CBE) closure without osteotomy. Still, many patients require osteotomy if they have a large bladder template and pubic diastasis, or non-malleable pelvis. To understand the indications and outcomes of bladder closure with and without pelvic osteotomy in patients younger than 1 month of age. An institutional database of 1217 exstrophy-epispadias patients was reviewed for CBE patients closed at the authors' institution within the first month of life. Patient demographics, closure history, pubic diastasis distance, bladder capacity, and outcomes were recorded and compared using chi-square tests between osteotomy and non-osteotomy patients. Failure was defined as bladder dehiscence, prolapse, vesicocutaneous fistula, or bladder outlet obstruction requiring reoperation. Bladder capacity >100 mL was deemed sufficient for bladder neck reconstruction (BNR). One hundred CBE patients were included for analysis: 38 closed with osteotomy (26 male, 12 female), and 62 closed without osteotomy (42 male, 20 female). There were four failed closures in the osteotomy group (2 dehiscence, 2 prolapse) and four failed closures in the non-osteotomy group (2 dehiscence, 2 prolapse). This corresponded to statistically equivalent rates of failure between the osteotomy and non-osteotomy groups (10.5% vs. 6.5%, p = 0.466). There was no statistically significant difference between the groups' ability to achieve bladder capacity sufficient for BNR (82% vs. 71%, p = 0.234). A successful primary bladder closure, regardless of the use of osteotomy, has been shown to be the single most important predictor of eventual continence. Because of the complexity of exstrophy manifestations, a multidisciplinary team approach is of the utmost importance. Based on our institutional experience, closure without osteotomy is considered when patients are <72 h of life, have a pubic diastasis <4 cm, malleable pelvis, and pubic apposition without difficulty. Rates of successful closure and attaining sufficient capacity for BNR were both statistically equivalent across groups. This retrospective study is limited by selection bias and the significant difference in follow-up time between groups. Nevertheless, as a high-volume exstrophy center this study draws from one of the largest cohorts available. Regardless of the type of closure undertaken, there clearly is a role for newborn CBE closure without pelvic osteotomy in patients considered suitable for closure by both the pediatric urologist and orthopedic consultant. However, if there is any doubt concerning pubic diastasis width, pelvic malleability, or ease of pubic apposition, an osteotomy is highly recommended.

Secondary Reclosure in Classic Bladder Exstrophy: Challenges and Outcomes

To analyze the outcomes of failed classic bladder exstrophy (CBE) reclosure with and without pelvic osteotomy. Each failed CBE closure decreases the chance of eventual continence. To minimize secondary failures, most institutions use pelvic osteotomy with reclosure. Reclosure with and without osteotomy can still fail. An institutional database of 1210 exstrophy-epispadias complex patients was reviewed for CBE patients who had 2 prior failed closures with the third closure at the authors' institution. Patient demographics, closure history, diastasis distance, bladder capacity, and outcomes were examined by chi-square tests comparing osteotomy status with first reclosure. Of 848 CBE patients, 17 met inclusion criteria: 12 with osteotomy at reclosure (group 1) and 5 without (group 2). Median time between initial closure and reclosure in the 2 groups were 6.5 months (range, 0-42 months) and 3 months (range, 0-59 months), respectively. There was no significant difference in the rate of attaining sufficient bladder capacity for bladder neck reconstruction (BNR; 100 cc) between groups 1 and 2 (42% vs 40%; P = .490). Within group 1, patients receiving proper immobilization with external fixation (n = 5) demonstrated a significantly greater rate of attaining sufficient bladder capacity for BNR compared with patients who did not (80% vs 14%; P = .023). There were no differences in the rates of attaining dryness per urethra. CBE outcomes worsen with each successive failed closure. Reclosure should be performed with osteotomy and proper immobilization to maximize the chance of sufficient capacity for BNR or augmentation cystoplasty.

Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy.

The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and is thought to result from aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify susceptibility loci for CBE, we performed a genome-wide association study (GWAS) of 110 CBE patients and 1,177 controls of European origin. Here, an association was found with a region of approximately 220kb on chromosome 5q11.1. This region harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region showed evidence for association with CBE, including 84 markers with genome-wide significance. We then performed a meta-analysis using data from a previous GWAS by our group of 98 CBE patients and 526 controls of European origin. This meta-analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at this locus reached genome-wide significance in the meta-analysis, and the most significant marker (rs9291768) achieved a P value of 2.13 × 10−12. No other locus in the meta-analysis achieved genome-wide significance. We then performed murine expression analyses to follow up this finding. Here, Isl1 expression was detected in the genital region within the critical time frame for human CBE development. Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the urorectal septum. The present study identified the first genome-wide significant locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the hypothesis that ISL1 is the responsible candidate gene in this region.

Urologic complications of major genitourinary reconstruction in the exstrophy–epispadias complex

ObjectiveTo present the authors' experiences with urologic complications associated with various techniques used to create a continent stoma (CS), augmentation cystoplasty (AC), and neobladder in the exstrophy–epispadias complex (EEC) population. MethodsRetrospective review of medical records of patients who underwent CS with or without bladder augmentation were identified from an institutional review board-approved database of 1208 EEC patients. Surgical indications, tissue type, length of hospital stay, age, preoperative bladder capacity, prior genitourinary surgeries, postoperative urological complications, and continence status were reviewed. ResultsAmong the EEC patients reviewed, 133 underwent CS (80 male, 53 female). Mean follow-up time after initial continent stoma was 5.31 years (range: 6 months to 20 years). Appendix and tapered ileum were the primary bowel segments used for the continent channel and stoma in the EEC population. The most common stomal complications in this population were stenosis, incontinence, and prolapse. Seventy-nine percent of EEC CS patients underwent AC primarily done with sigmoid colon or ileum. Eleven patients (8%) underwent neobladder creation with either colon or a combination of colon and ileum. Bladder calculi, vesicocutaneous fistula, and pyelonephritis were the most common non-stomal complications. Stomal ischemia was significantly increased in Monti ileovesicostomy compared to Mitrofanoff appendicovesicostomy in classic bladder exstrophy patients (p = 0.036). Furthermore, pyelonephritis was more than twice as likely in colonic neobladder than all other reservoir tissue types in the same cohort (OR = 2.53, 95% CI: 1.762–3.301, p < 0.001). ConclusionsTo the best of the authors' knowledge, this is the largest study examining catheterizable stomas in the exstrophy population. While Mitrofanoff appendicovesicostomy is preferred to Monti ileovesicostomy because it is technically less challenging, it may also confer a lower rate of stomal ischemia. Furthermore, even though ileum or colon can be used in AC with equally low complication rates, practitioners must be wary of potential urologic complications that should be primarily managed by an experienced reconstructive surgeon.

Classic bladder exstrophy: Frequent 22q11.21 duplications and definition of a 414 kb phenocritical region.

Classic bladder exstrophy (CBE) is the most common form of the bladder exstrophy and epispadias complex. Previously, we and others have identified four patients with a duplication of 22q11.21 among a total of 96 unrelated CBE patients. Here, we investigated whether this chromosomal aberration was commonly associated with CBE/bladder exstrophy and epispadias complex in an extended case-control sample. Multiplex ligation-dependent probe amplification and microarray-based analysis were used to identify 22q11.21 duplications in 244 unrelated bladder exstrophy and epispadias complex patients (including 217 CBE patients) and 665 healthy controls. New duplications of variable size were identified in four CBE patients and one control. Pooling of our previous and present data (eight duplications in 313 CBE patients) yielded a combined odds ratio of 31.86 (95% confidence interval, 4.24-1407.97). Array-based sequence capture and high-throughput targeted re-sequencing established that all breakpoints resided within the low-copy repeats 22A to 22D. Comparison of the eight duplications revealed a 414 kb phenocritical region harboring 12 validated RefSeq genes. Characterization of these 12 candidate genes through whole-mount in situ hybridization of mouse embryos at embryonic day 9.5 suggested that CRKL, THAP7, and LZTR1 are CBE candidate genes. Our data suggest that duplication of 22q11.21 increases CBE risk and implicate a phenocritical region in disease formation.

Delayed exstrophy repair (DER) does not compromise initial bladder development

ObjectiveDelayed exstrophy repair (DER) represents an alternative to early neonatal bladder closure. This study aims to define the consequence of DER on bladder growth in bladder exstrophy patients who underwent routine DER, compared with those who underwent immediate postnatal reconstruction. MethodsBetween 2000 and 2005, classic bladder exstrophy patients referred to the authors' institution underwent early neonatal bladder closure (group 1). Subsequently, classic bladder exstrophy patients referred to the authors' institution were treated with an elective DER (group 2). Bladder capacity was assessed between the age of 1 and 4 years with an unconscious cystogram. When dilating VUR was present, the volume of the contrast migrated into the ureter was calculated and subtracted. ResultsSixty patients were treated between 2000 and 2012. Complete follow-up data were available for 45 patients and they were included in the study: 21 in group 1 (11 males) and 24 in group 2 (14 males). The mean (SD) bladder volumes were 72.85 (28.5) ml in group 1 and 72.87 (34.9) in group 2 (p = 0.99). ConclusionIn the authors' experience, DER does not reduce the subsequent bladder capacities compared with neonatal exstrophy closure.

Shortened pubic bones in bladder exstrophy: A congenital or acquired phenomenon?

ObjectiveIt is accepted that the length of the anterior segment of the pelvis in classic bladder exstrophy is shorter than that of controls. However, studies performed involve children with a wide range of ages. By studying children with classic bladder exstrophy under the age of 1 year, the authors aim to ascertain if there is a congenital pubic bone length discrepancy associated with bladder exstrophy. Material and methodsFourteen classic bladder exstrophy patients under 1 year of age and 14 age-matched controls were identified. Three-dimensional (3D) computerized tomography was used to measure the length of the superior pubic ramus bilaterally. In the exstrophy group, scans were performed before bladder closure. The Mann–Whitney U test was used and p < 0.05 was considered significant. ResultsThere was no significant difference (p = 0.76) in the median age in cases (72 days) and controls (64 days). The median superior pubic ramus length was 19.1 mm in the exstrophy group and 20 mm in the control group (p = 0.99). ConclusionsSuperior pubic ramus length in children under 1 year of age with classic bladder exstrophy is not statistically different from that in control subjects. Therefore, the authors hypothesize that the previously described shortening of the pubic bones is an acquired phenomenon, which may develop after the first year of life.

The role of osteotomy in surgical repair of bladder exstrophy

Classic bladder exstrophy (CBE) patients are born with a pubic diastasis that increases steadily with age from a mean value of 4 cm at birth to a mean of 8 cm at age 10, compared with a mean normal width of the pubic symphysis of 0.6 cm at all ages. The width of the sacrum and length of the posterior (iliac) segment of the pelvis in CBE patients are normal; however, the anterior (ischiopubic) segment of the pelvis is a mean 30% shorter and both the anterior and posterior segments are externally rotated compared to controls. The main role of osteotomy in treatment of CBE appears to be to relax tension on the bladder and repaired abdominal wall during wound-healing. Anterior innominate osteotomy with optional posterior vertical iliac osteotomy presents several advantages over the prior conventional technique of posterior iliac osteotomy. These include (a) less intraoperative blood loss, (b) better apposition and mobility of the pubic rami at the time of closure, (c) allowance for placement of an external fixator under direct vision, (d) allowance for secure external fixation in children over 6 months old, and (e) no requirement to turn the patient during the operation.

Editorial Comment

The authors have presented the case for the use of internal fixation after osteotomies used in the soft tissue reconstruction of exstrophy. I hope the authors continue their evaluation of this technique compared with other standard techniques in reference to clinically important questions regarding body image, penile size, and orthopedic concerns. Without any data to support the use of fixation, we have not embraced internal fixation at our institution out of concerns regarding erosion of the fixation device or the fixation screws into the bladder neck and surrounding soft tissues. This paper will stimulate us to revisit this discussion with our orthopedic colleagues. Three-dimensional Anatomy of the Pelvic Bone in Bladder Exstrophy: Comparison Between Patients Managed With Osteotomy and Pubic Symphysis Internal Fixation Using Metal PlatesUrologyVol. 76Issue 4PreviewTo compare intrapelvic osseous dimensions in classic bladder exstrophy patients who underwent pelvic osteotomy and pubic symphysis internal fixation, using metal plates without osteotomy by defining intrapelvic angles and distances using three-dimensional computed tomography scan (3D-CT). Full-Text PDF ReplyUrologyVol. 76Issue 4PreviewCurrently, we have used internal fixation of the pubic arch as a crucial prerequisite for optimal pubic secure closure in our exstrophy patients. Initially, we evaluated the outcomes of pubic bone approximation and internal fixation using a miniature metal plate and screws.1 Although during our 5-year follow-up, only one case of metal plate dislocation was detected, the concerns of probable tissue reactions, metal corrosion, and the need for a second operation for plate removal prompted us to apply a biodegradable fixation system as an effective alternative to metal plates. Full-Text PDF