Classic Bladder Exstrophy Research Articles

Superior Vesical Fissure as an Incomplete Form of Bladder Exstrophy: A Case Report with Clinico-Pathological Correlation and a Comprehensive Literature Review.

Multiple variants of classic bladder exstrophy have been described, all of them infrequent. Superior vesical fissure is a mild variant of this pathology in which genital involvement is scarce or absent. To date, there are only isolated reports of this entity. We report a full-term female patient of Arabian descent with a clinical and radiological diagnosis of superior vesical fissure that was surgically corrected in our center with a favorable evolution. Histological study, supported by immunohistochemical techniques, showed squamous and transitional epithelium and discrete chronic inflammation. Our literature review identified 26 reports of superior vesical fissure (including ours), with high heterogeneity in terms of clinical characterization and associated malformations and with only two histological reports. The clinical evolution of the patients reported in the literature was favorable, with lower morbidity and mortality than in classical forms of bladder exstrophy.

Classic Bladder Exstrophy Closure Without Osteotomy or Immobilization: An Exercise in Futility?

To review the outcomes of classic bladder exstrophy (CBE) closure without the use of osteotomy or lower extremity/pelvic immobilization. A prospectively maintained institutional approved exstrophy-epispadias complex database of 1487 patients was reviewed for patients with CBE who had undergone closure without osteotomy nor immobilization. All patients were referred to the authors' institution for reconstruction later in life or for failed closure. Of a total of 1016 CBE patients, 56 closure events were identified that met inclusion with a total of 47 unique patients. Thirty-eight closures were completed prior to 1990 (67.9%). Forty-five closure events developed eventual failure (45/56, 80.4%) (Table 1). Thirteen closure events were secondary closures (13/56, 23.2%). The primary closure failure rate was 83.7% (36/43) while the secondary closure failure rate was 69.2% (9/13). Failures were attributed to one or more of dehiscence, bladder prolapse, and vesicocutaneous fistula (25/45, 55.6%) (23/45, 51.1%) (6/45, 13.3%), respectively. Thirty-seven patients developed social continence (37/47, 78.7%), while only 8 patients developed spontaneous voided continence (7/47,17.0%) (Table 2). The most common methods of voiding were continent catheterizable channels (25/47, 53.2%) of which all were socially continent. These results illustrate the critical role osteotomy and postoperative immobilization can play in both primary and secondary exstrophy closure. While this is a historical case series, the authors believe that these results remain relevant to contemporary exstrophy surgeons.

Presentations of bladder exstrophy in a resource-limited setting and the role of Mainz II continent diversion for late referrals or failed primary closures: a multicentric report.

Primary closure techniques that have been updated and longterm follow-up for CBE (classic bladder exstrophy) may be out of reach for many patients living in resource-limited settings. Late referrals to medical care and primary closures that lack the necessary skills and facilities for comprehensive treatment are still common. Alternative and long-term surgical solutions may improve the lives of these unfortunate patients. During surgical outreach missions, patients with CBE, either non-operated or with a previous unsuccessful bladder closure, who were referred from vast under-resourced rural areas to three Eastern African hospitals, were studied. The following information is provided: mode of presentation, clinical history, diagnostic workout, management, and outcome. There were 25 cases (M/F ratio 17/8) ranging in age from two days to twenty years. Five of the seventeen patients who were not treated (35%) were under 120 days old and eligible for primary closure in a qualified tertiary center when one was available in the country. There were twelve late referred cases (ranging from 120 days to 20 years). Between the ages of ten months and twelve years, eight children arrived following a failed primary closure. In all of them, the bladder plate was too altered to allow closure. Following a preoperative diagnostic workout, a Mainz II continent internal diversion was proposed to fourteen patients with acceptable bowel control and postponed in the other three. Three cases were lost before treatment because parents refused the procedure. Twelve cases ranging in age from three to twenty years (mean seven years) were operated on. Eight people were followed for a total of 53.87 months (range: 36-120). Except for three people who complained of occasional night soiling, day and night continence were good. The average voiding frequency during the day was four and 1.3 at night. There was no evidence of a metabolic imbalance, urinary infection, or significant upper urinary tract dilatation. Two fatalities could not be linked to urinary diversion. Four patients were not followed up on. Due to the limited number of specialist surgical facilities, CBE late referral or failed closure is to be expected in a resource-limited context. In lieu of the primary closure, a continent internal diversion will be proposed and encouraged even at the level of a non-specialist hospital to improve the quality of life of these unfortunate patients. It is recommended that patients be warned about the procedure's potential long-term risks, which will necessitate a limited but regular follow-up.

The outcome and complications of modern staged repair surgery in newborns with classic bladder exstrophy in different genders: A retrospective study.

Classic bladder exstrophy (CBE) is a rare anterior midline birth defect that remains a challenge for pediatric surgeons. Despite multiple reconstructive methods, outcomes vary widely in various reports. This study aims to compare the success rate and complications of modern staged repair of exstrophy (MSRE) in each gender and compare together. This retrospective cross-sectional study included cases of CBE between 2010 and 2020 that underwent MSRE. Short-term follow-up results, including incontinence rate, vesicoureteral reflux (VUR), urinary infections, deformed genitalia, and so on, were measured in each gender, and their differences were reported. Among the 40 newborns with CBE who underwent MSRE, 25 (62.5%) were boys, while the others had non-male genitalia. The rates of incontinence, VUR, dehiscence, and fistulas did not differ significantly between genders. However, chronic urinary tract infections (UTIs) were more frequent in girls, and boys were more likely to have malformed genitalia (p < .05). Our findings indicate a similar rate of complications in each gender. However, chronic UTIs and external genitalia deformities were significantly more common in girls and boys, respectively. Further large-sized controlled trials may be needed to corroborate these findings.

Exome Survey and Candidate Gene Re-Sequencing Identifies Novel Exstrophy Candidate Genes and Implicates LZTR1 in Disease Formation.

The bladder exstrophy-epispadias complex (BEEC) is a spectrum of congenital abnormalities that involves the abdominal wall, the bony pelvis, the urinary tract, the external genitalia, and, in severe cases, the gastrointestinal tract as well. Herein, we performed an exome analysis of case-parent trios with cloacal exstrophy (CE), the most severe form of the BEEC. Furthermore, we surveyed the exome of a sib-pair presenting with classic bladder exstrophy (CBE) and epispadias (E) only. Moreover, we performed large-scale re-sequencing of CBE individuals for novel candidate genes that were derived from the current exome analysis, as well as for previously reported candidate genes within the CBE phenocritical region, 22q11.2. The exome survey in the CE case-parent trios identified two candidate genes harboring de novo variants (NR1H2, GKAP1), four candidate genes with autosomal-recessive biallelic variants (AKR1B10, CLSTN3, NDST4, PLEKHB1) and one candidate gene with suggestive uniparental disomy (SVEP1). However, re-sequencing did not identify any additional variant carriers in these candidate genes. Analysis of the affected sib-pair revealed no candidate gene. Re-sequencing of the genes within the 22q11.2 CBE phenocritical region identified two highly conserved frameshift variants that led to early termination in two independent CBE males, in LZTR1 (c.978_985del, p.Ser327fster6) and in SLC7A4 (c.1087delC, p.Arg363fster68). According to previous studies, our study further implicates LZTR1 in CBE formation. Exome analysis-derived candidate genes from CE individuals may not represent a frequent indicator for other BEEC phenotypes and warrant molecular analysis before their involvement in disease formation can be assumed.

Urethral Plate Grafting for Deficient Urethral Plate in Exstrophy: An Alternative Method to Augment Urethral Plate

IntroductionShort urethral plate remains a challenge in exstrophy management. We report our experience with urethral plate grafting in cases of exstrophy with deficient urethral plate. MethodsAmong the exstrophy patients treated at the authors’ institutions (2018–2022), those with a short urethral plate were prospectively included. A short urethral plate was defined as a distance between the verumontanum and the base of the glans of less than 10 mm. Urethral plate grafting was performed electively before the exstrophy closure. The urethral plate was divided just distal to verumontanum, and a thin inner preputial or para-exstrophy skin graft was harvested and deployed to cover the defect. Exstrophy closure was subsequently performed. The following parameters were recorded: age at grafting, type of graft and age at exstrophy closure. Reported outcomes include success of closure, complications, and follow up. ResultsSix male patients were included in the study: 3 classic bladder exstrophy (CBE) and 3 cloacal exstrophy (CE). Median age at grafting was 9 (3–18) months. Inner preputial grafts were utilized in the 3 CBE patients, and para-exstrophy skin grafts were used for the 3 CE patients. There was no graft loss, and longer and wide urethral plate was seen in all cases. Median time to bladder exstrophy closure was 3 (3–13) months after grafting. ConclusionPre-closure urethral plate grafting represents a safe and effective option for exstrophy patients with a short or inadequate urethral plate.

Mucosal Violations and Their Effect on Successful Bladder Neck Closure in Cloacal Exstrophy

BackgroundCloacal exstrophy (CE) is rare and challenging to reconstruct. In the majority of CE patients voided continence cannot be achieved and so patients often undergo bladder neck closure (BNC). Prior mucosal violations (MVs), a surgical event when the bladder mucosa was opened or closed, significantly predicted failed BNC in classic bladder exstrophy with an increased likelihood of failure after 3 or more MVs. The aim of this study was to assess predictors for failed BNC in CE. MethodsCE patients who underwent BNC were reviewed for risk factors for failure including osteotomy use, successful primary closure, and number of MVs. Chi-squared and Fisher's exact tests were used for comparing baseline characteristics and surgical details. ResultsThirty-five patients underwent BNC. Eleven patients (31.4%) failed BNC including a vesicoperineal fistula in nine, vesicourethral and vesicocutaneous fistula in one each. The fistula rate in patients with 2 or more MVs was 47.4% (p = 0.0252). Two patients subsequently developed a vesicocutaneous fistula after undergoing repeated cystolithotomies. A rectus abdominis or gracilis muscle flap were used to close the fistula in 11 and 2 patients, respectively. ConclusionsMVs have a greater impact in CE with an increased risk of failed BNC after 2 MVs. CE patients are most likely to develop a vesicoperineal fistula while a vesicocutaneous fistula is more likely after repeat cystolithotomy. A prophylactic muscle flap should be considered at time of BNC in patients with 2 or more MVs. Levels of EvidencePrognosis Study, Level III.

Bladder capacity and growth in classic bladder exstrophy: A novel predictive tool

Bladder capacity (BC) is an important metric in the management of patients with classic bladder exstrophy (CBE). BC is frequently used to determine eligibility for surgical continence procedures, such as bladder neck reconstruction (BNR), and is associated with the likelihood of achieving urinary continence. To use readily available parameters to develop a nomogram that could be used by patients and pediatric urologists to predict BC in patients with CBE. An institutional database of CBE patients was reviewed for those who have undergone annual gravity cystogram 6 months after bladder closure. Candidate clinical predictors were used to model BC. Linear mixed effects models with random intercept and slope were used to construct models predicting log transformed BC and were compared with adjusted R2, Akaike Information Criterion (AIC), and cross-validated mean square error (MSE). Final model evaluated via K-fold cross-validation. Analyses were performed using R version 3.5.3 and the prediction tool was developed with ShinyR. In total, 369 patients (107 female, 262 male) with CBE had at least one BC measurement after bladder closure. Patients had a median of 3 annual measurements (range 1-10). The final nomogram includes outcome of primary closure, sex, log-transformed age at successful closure, time from successful closure, and interaction between outcome of primary closure and log-transformed age at successful closure as the fixed effects with random effect for patient and random slope for time since successful closure (Extended Summary). Using readily accessible patient and disease related information, the bladder capacity nomogram in this study provides a more accurate prediction of bladder capacity ahead of continence procedures when compared to the age-based Koff equation estimates. A multi-center study using this web-based CBE bladder growth nomogram (https://exstrophybladdergrowth.shinyapps.io/be_app/) will be needed for widespread application. Bladder capacity in those with CBE, while known to be influenced by a broad swath of intrinsic and extrinsic factors, may be modeled by the sex, outcome of primary bladder closure, age at successful bladder closure and age at evaluation.

Achieving goal capacity for continence surgery: A cumulative event analysis of bladder exstrophy patients

Following successful closure of patients with classic bladder exstrophy (CBE), the next major milestone is the establishment of urinary continence. Prior to determining the most appropriate continence surgery, it is imperative to reach an adequate bladder capacity minimum of 100cc in order to make the decision between bladder neck reconstruction (BNR) or continent stoma, with or without augmentation cystoplasty (AC). To examine the timing of when patients achieve threshold bladder capacity for BNR eligibility. We hypothesize most patients will achieve an adequate bladder capacity (100cc) by 7 years old when continence surgeries will begin to be considered. An institutional database of 1388 exstrophy patients was retrospectively reviewed for CBE patients after successful primary bladder closure. Bladder capacities were measured via gravity cystography and data presented as descriptive statistics. The cohort was stratified by location, neonatal (≤28 days) or delayed closure period and osteotomy status. The bladder capacities were categorized to either reaching goal or not and a cumulative event analysis was performed. The event being reaching 100cc capacity or greater and time being the number of years between bladder closure and attainment of goal capacity. 253 patients met inclusion criteria between 1982 and 2019. The majority were of male gender (72.9%), had their closure performed at the authors' institution (52.5%), within the neonatal period (80.7%), and without an osteotomy (51.7%). 64.9% of patients reached goal bladder capacity. There were no significant differences in those who did or did not achieve goal except for clinical follow up. Cumulative event analysis demonstrated a median time of 5.73 years (95% CI 5.2-6.20) corresponded with a 50% event probability of reaching goal capacity. Cox-proportional hazards showed location of closure was significantly associated with hazards of reaching goal bladder capacity (HR=0.58, CI 0.40-0.85, p=0.005). Based on this model, the median time to event would be 5.20 years (95% CI 4.76-5.80) for cases done at the authors' hospital and 6.26 years for those performed at an outside hospital (95% CI 5.77-7.24). These findings help surgeons counsel families appropriately on the odds of attaining goal capacity at various ages. For those who do not reach 100cc by five years of age, it helps further characterize the odds of requiring a continent stoma with bladder augmentation and the best timing for reconstructive surgery in order to safely gain urinary continence. Families may also be assured that most patients would have the breadth of surgical options when it comes to continence as more than half of patients reached the bladder capacity threshold.

The impact of repeated bladder surgery on successful bladder neck closure in classic bladder exstrophy: The role of mucosal violations

Restoration of genitourinary anatomy with functional urinary continence is the reconstruction aim is the exstrophy-epispadias complex (EEC). In patients who do not achieve urinary continence or those who are not a candidate for bladder neck reconstruction (BNR), bladder neck closure (BNC) is considered. Interposing layers including human acellular dermis (HAD) and pedicled adipose tissue are routinely placed between the transected bladder neck and distal urethral stump to reinforce the BNC and minimize failure due to fistula development from the bladder. The aim of this study was to review classic bladder exstrophy (CBE) patients who underwent BNC to identify predictors of BNC failure. Specifically, we hypothesize that increased operations on the bladder urothelium leads to a higher rate of urinary fistula. CBE patients who underwent BNC were reviewed for predictors of failed BNC which was defined as bladder fistula development. Predictors included prior osteotomy, interposing tissue layer use and number of previous bladder mucosal violations (MV). A MV was defined as a procedure when the bladder mucosa was opened or closed for: exstrophy closure(s), BNR, augmentation cystoplasty or ureteral re-implantation. Predictors were evaluated using multivariate logistic regression. A total of 192 patients underwent BNC of which 23 failed. Patients were more likely to develop a fistula with a wider pubic diastasis at time of primary exstrophy closure (4.4 vs 4.0 cm, p=0.0016), have failed exstrophy closure (p=0.0084), or have 3 or more MVs before BNC (p=0.0002). Kaplan-Meier analysis of fistula-free survival after BNC, demonstrated an increased fistula rate with additional MVs (p=0.0004, Figure1). MVs remained significant on multivariate logistic regression analysis with a per-violation odds ratio of 5.1 (p<0.0001). Of the 23 failed BNC's, 16 were surgically closed including 9 using a pedicled rectus abdominis muscle flap which was secured to the bladder and pelvic floor. This study conceptualized MVs and their role in bladder viability. Increased MVs confer an increased risk of failed BNC. When considering BNC, CBE patients with 3 or more prior MVs may benefit from a pedicled muscle flap, in addition to HAD and pedicled adipose tissue, to prevent fistula development by providing wellvascularized coverage to further reinforce the BNC.

Spinal dysraphism in exstrophy: a single-center study of a 39-year prospective database.

The two main objectives of this study were to explore the rate of spinal dysraphism within bladder and cloacal exstrophy and to analyze the relationship between spinal dysraphism surgery, including timing of spinal dysraphism surgery, with urological and neurological outcomes. A prospectively maintained IRB-approved database of pediatric exstrophy patients treated from 1982 to 2021 was retrospectively reviewed for patients with spinal dysraphism. Spinal dysraphism was categorized into the following 7 subtypes: lipoma-based closed defect, myelomeningocele, meningocele, diastematomyelia, myelocystocele, low-lying conus with tethered cord/fatty filum, and sacral bony defect. Other factors assessed included patient demographic characteristics, type of spinal dysraphism procedure, reoperation, complication, presence of other neurological problems (e.g., hydrocephalus, Chiari malformation), neurological status, and urological function. Analysis revealed that 114/1401 patients had coexisting spinal dysraphism. Of these 114, sufficient records including type of dysraphism were available for 54. Spinal dysraphism was most common within cloacal exstrophy (83.3% [45/54 patients]), followed by cloacal exstrophy variants (9.3% [5/54]), classic bladder exstrophy (3.7% [2/54]), and classic bladder exstrophy variants (3.7% [2/54]). Within spinal dysraphism, lipoma-based closed defects (63.0% [34/54]) and low-lying conus with tethered cord/fatty filum (11.1% [6/54]) were most common. Hydrocephalus and Chiari malformation occurred in 24.1% (13/54) and 11.1% (6/54) of patients. All 13 patients with hydrocephalus underwent shunt placement. Among those who underwent neurosurgical intervention, the complication rate for spinal dysraphism was 14.6% (7/48). Motor function data were available for 41 patients and revealed that motor function declined for 2/41 (4.8%) patients and improved for 6/41 (14.6%) after neurosurgery. There was no statistical difference in lower-extremity motor outcome related to timing of neurosurgery and exstrophy closure. The authors have reported the surgical management and outcomes of patients with exstrophy and coexisting spinal dysraphism (n = 54). In 54 patients, spinal dysraphism was most common in the subset of patients with cloacal exstrophy (83.3%). Lipoma-based closed defects (63.0%) and low-lying conus with tethered cord/fatty filum (11.1%) were the most common, and the rates of hydrocephalus and Chiari malformation were 24.1% and 11.1%, respectively. There was no difference in lower-extremity motor outcome related to timing of neurosurgery and exstrophy closure.

V04-01 NOVEL UTILIZATION OF INDOCYANINE GREEN TO ASSESS BLADDER PLATE AND PENILE PERFUSION DURING BLADDER EXSTROPHY CLOSURE

You have accessJournal of UrologyCME1 Apr 2023V04-01 NOVEL UTILIZATION OF INDOCYANINE GREEN TO ASSESS BLADDER PLATE AND PENILE PERFUSION DURING BLADDER EXSTROPHY CLOSURE Amanda Raines, Nicolas Fernandez, Jennifer Ahn, Margarett Shnorhavorian, Hailey Silverii, and Paul Merguerian Amanda RainesAmanda Raines More articles by this author , Nicolas FernandezNicolas Fernandez More articles by this author , Jennifer AhnJennifer Ahn More articles by this author , Margarett ShnorhavorianMargarett Shnorhavorian More articles by this author , Hailey SilveriiHailey Silverii More articles by this author , and Paul MerguerianPaul Merguerian More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003252.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Reconstruction of bladder exstrophy poses a unique challenge to urologic surgeons. At our institution the current practice is to perform complete primary repair of bladder exstrophy (CPRE). However, there have been concerns about compromise of penile perfusion using this technique with reports of penile or glans loss due to ischemia. Currently, one method of penile perfusion assessment after closure is completed is a needlestick to the glans to observe for bleeding, however, this provides limited and subjective information. Indocyanine green or ICG is a fluorescent dye which has been in use since the 1950s. With a short half-life and favorable safety profile, it is ideal for intraoperative use. It has been widely used throughout the surgical community to assess tissue perfusion, but its use within pediatric urology has been limited and not standardized. To our knowledge, ICG use in bladder exstrophy has not been previously described. We aim to describe our approach to CPRE with use of ICG and detail our intraoperative findings. METHODS: An otherwise healthy four month old male with classic bladder exstrophy was taken to the operating for bladder closure with CPRE. ICG was given in three doses first after complete penile degloving, next after complete mobilization of the corpora and take down of intersymphyseal bands, and finally after osteotomy and pubic symphysis approximation. Quantification software is used to measure ICG uptake at each stage. RESULTS: ICG uptake in the glans remained symmetric and around 100% at the time of the first and second doses. However, uptake on the third dose was significantly decreased and asymmetric with the right glans having an uptake of 20-30% and the left 40-50%. CONCLUSIONS: The current standard of penile perfusion assessment with a needle stick to the glans is subjective and limited in the detail it provides. More updated methods like ICG can generate an objective quantitative and more detailed assessment which could be useful in complex reconstructions such as bladder exstrophy closure. While more data is currently needed than this single experience, future applications of ICG may alter surgical decision making such as loosening of the symphyseal sutures to improve penile perfusion. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e338 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amanda Raines More articles by this author Nicolas Fernandez More articles by this author Jennifer Ahn More articles by this author Margarett Shnorhavorian More articles by this author Hailey Silverii More articles by this author Paul Merguerian More articles by this author Expand All Advertisement PDF downloadLoading ...

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

ObjectiveTo test the hypothesis that phenotypes in bladder exstrophy result from alterations in detrusor smooth muscle cell (SMC) gene expression. MethodsWe 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). ResultsWe 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. ConclusionBladder 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.

A Single Center's Changing Trends in the Management and Outcomes of Primary Closure of Classic Bladder Exstrophy: An Evolving Landscape

To investigate management trends in a single institution with a large referral population in classic bladder exstrophy (CBE) over the past twenty years. An institutional database of 1415 exstrophy-epispadias complex patients was retrospectively reviewed for CBE patients with primary closure between 2000 and 2019. Osteotomy, location of closure, age of closure, and outcome of closures were reviewed. A total of 278 primary closures were identified, with 100 occurring at author's hospital (AH) and 178 at outside hospitals (OSH). Osteotomies were performed in 54% of cases at AH and 52.8% of cases at OSH. Osteotomy use increased over 20 years from 48.6% in 00's to 62.1% in 10's (p=0.046). The total success rate at AH was 96% and 62.9% at OSH. The median age at primary closure at AH increased from 5 days (00's) to 20 days (10's), compared to the OSH which increased from 2 days (00's) to 3 days (10's). Closure of CBE may be delayed for several reasons including insurance difficulties, transfer to another hospital, desire for second opinions, or surgeon preference. Delaying primary closure of bladder exstrophy gives families time to adjust lifestyle, arrange travel, and seek care at centers of excellence.

Urinary Bladder Cancer in Bladder Exstrophy and Epispadias Complex: A Swedish Register Study and a Systematic Review of the Literature

Abstract The congenital malformation bladder exstrophy and epispadias complex involves multiple organs and includes 3 subtypes: epispadias, classic bladder exstrophy, and cloacal exstrophy. The risk of urinary bladder cancer is known to be higher in individuals with classic bladder exstrophy and appears at a younger age compared with the general population. Purpose: The purpose of this study was to evaluate urinary bladder cancer in individuals with bladder exstrophy and epispadias complex. Materials and Methods: We performed 2 studies, a Swedish register-based case series reporting 12 novel cases and a systematic review summarizing published cases thus far. MEDLINE, EMBASE, Web of Science, and Google Scholar were searched in January 2022 following the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Publications reporting at least 1 case of bladder exstrophy and epispadias complex with urinary bladder cancer were eligible. Ninety-seven publications were included, reporting 165 cases. Results: The main result from the register study was the tumors being predominantly urothelial. Conversely, earlier published cases from the literature had a nonurothelial tumor type in 95%, whereof the majority were adenocarcinomas. Both substudies consistently indicate a young age at cancer diagnosis, with the majority being younger than 65 years. Conclusions: Urinary bladder cancer affects individuals with bladder exstrophy and epispadias complex at a young age. The most common tumor type in the register study is urothelial. The divergence between the 2 substudies in tumor types could reflect a slightly older age in our case series, likewise a possible publication bias.

Evaluation of Early Postoperative Outcome of Success of Repair of One Stage Repair of Bladder Exstrophy

Bladder exstrophy is a rare congenital anomaly of the genitourinary tract producing ventral abdominal wall defect. Previously; it was operated by a multi-stage procedure. In the course of time, the repair of bladder exstrophy has evolved from a staged repair to a one-stage reconstruction with encouraging results in different countries. One-stage repair of bladder exstrophy is being practiced since 2007 in BSMMU. So; this study was conducted on one-stage repair of bladder exstrophy to observe early possible outcomes.&#x0D; Methods: This prospective observational study was conducted at BSMMU on ten postoperative cases of Classic bladder Exstrophy who underwent one-stage repair from September 2018 to October 2021.&#x0D; Results: Results show that 10% of the subjects developed wound dehiscence. The mean hospital stay was 18.9 days.&#x0D; Conclusion: From the results found in this study, one-stage repair of bladder exstrophy achieved success in bladder, and abdominal wall reconstruction, as evidenced by the rate of wound dehiscence is comparably similar. Moreover, one-stage of repair of bladder exstrophy appears to be better enough for broader practice. One-stage reconstruction minimizes the number of surgical procedures required to achieve the treatment goals, including normal genital cosmesis and safe postoperative outcome.

Evaluation of Early Postoperative Outcome of Success of Repair of One Stage Repair of Bladder Exstrophy

Bladder exstrophy is a rare congenital anomaly of the genitourinary tract producing ventral abdominal wall defect. Previously; it was operated by a multi-stage procedure. In the course of time, the repair of bladder exstrophy has evolved from a staged repair to a one-stage reconstruction with encouraging results in different countries. One-stage repair of bladder exstrophy is being practiced since 2007 in BSMMU. So; this study was conducted on one-stage repair of bladder exstrophy to observe early possible outcomes.&#x0D; Methods: This prospective observational study was conducted at BSMMU on ten postoperative cases of Classic bladder Exstrophy who underwent one-stage repair from September 2018 to October 2021.&#x0D; Results: Results show that 10% of the subjects developed wound dehiscence. The mean hospital stay was 18.9 days.&#x0D; Conclusion: From the results found in this study, one-stage repair of bladder exstrophy achieved success in bladder, and abdominal wall reconstruction, as evidenced by the rate of wound dehiscence is comparably similar. Moreover, one-stage of repair of bladder exstrophy appears to be better enough for broader practice. One-stage reconstruction minimizes the number of surgical procedures required to achieve the treatment goals, including normal genital cosmesis and safe postoperative outcome.

Complications of delayed and newborn primary closures of classic bladder exstrophy: Is there a difference?

The authors aim to compare single institutional 30-day complication rates between delayed and neonatal closure of classic bladder exstrophy (CBE). An institutional database of 1415 exstrophy-epispadias patients was reviewed retrospectively for CBE patients who underwent primary closures at the authors' institution between 1990 and 2020. Patients were identified as having received either neonatal or delayed (at age >28 days) closures. All 30-day complications were recorded, including wound infection and dehiscence, genitourinary and non-genitourinary infections, bowel obstruction, blood transfusions, and others. Descriptive statistics were performed to summarize patient level data. Categorical variables were reported by count and percentages and were compared using Exact Cochran-Armitage trend analysis by decade, or with Fisher's Exact Test and Chi-square test when directly comparing categories and outcomes. Continuous variables were analyzed via Mann Whitney U and one-way ANOVA as appropriate. The cohort included 145 patients: 50 delayed and 95 neonatal closures. The total complication rate was 58% in delayed closures compared to 48.4% for neonatal closures (p=0.298), with the majority being Clavien-Dindo grade I or II. Excluding blood transfusion, complication rates fell to 26% and 34.7% in delayed and neonatal closures, respectively (p=0.349). The most common single complication was unplanned post-operative blood transfusion (38% delayed; 26.3% neonatal; p=0.34), followed by pyelonephritis (2% delayed; 8.4% neonatal), and urinary fistula (6% delayed; 1.1% neonatal). Grade III Clavien-Dindo complications occurred in 2% delayed and 7.4% neonatal groups (n=1; n=7 respectively; p=0.263). A single delayed patient had grade IV complications compared to three neonatal patients (p=0.66). Delayed primary closure has become a frequently performed alternative in the modern treatment of bladder exstrophy for patients who do not undergo newborn closure because of prohibitive circumstances or surgeon's discretion. The majority of the complications associated with delayed closure are a low Clavien-Dindo grade and easily managed during the postoperative inpatient hospital stay. Families should be counseled about the possibility of minor, conservatively managed complications and likelihood of a blood transfusion with osteotomy.

Fixation with lower limb immobilization in primary and secondary exstrophy closure: A saving grace

A pivotal factor in the success of bladder closure in patients with classic bladder exstrophy (CBE) is the postoperative immobilization of the pelvis and lower extremities after pelvic osteotomy. This study investigates the outcomes of closure among patients with lower limb immobilization using many techniques. The authors hypothesize that the addition of external fixation (pelvic immobilization) in patients with any form of limb immobilization will be associated with improved outcomes. A prospectively maintained institutional exstrophy-epispadias complex database of 1415 patients was reviewed for patients with CBE who had undergone closure with available immobilization and osteotomy data. Association between closure outcomes and immobilization techniques were determined. Univariate analysis was performed using Chi-Square or Fischer-Exact test as appropriate for categorical variables. Multivariate analysis via binomial logistic regression was used to identify factors leading to successful closure. A total of 747 closure events matching the inclusion criteria were identified. Patients included 508 males and 239 females. There were 597 primary closures (79.9%) with 150 reclosure events (20.1%). Limb immobilization was used in 627 (83.9%) of closure events. Successful closures were associated with osteotomy use (p<0.0001) and limb immobilization (p<0.0001); specifically, the combined anterior innominate with posterior vertical iliac osteotomy and modified Buck's traction with external fixation (p<0.0001, p<0.0001). Among the group of 33 patients who received external fixation alone and no other type of immobilization, the failure rate was 33.3%, comparatively, patients with any form of combined immobilization (external fixation with lower limb immobilization) had a failure rate of 7.1% ( Table 1). Among patients immobilized with mummy wrap, spica casting, or knee immobilizers, external fixation was associated with 3.76 increased odds of successful closure (p=0.0005, 95% CI 1.79-7.90). In a unique group of 67 patients without pelvic osteotomy or any form of pelvic or limb immobilization, the failure rate was 74.6%. This study confirms, in a larger series, previous findings of improved outcomes when patients are immobilized with modified Buck's traction and external fixation. The authors apply this technique in most all closures and recommend this technique be utilized whenever feasible. However, regardless of the manner of lower limb immobilization, external fixation is a critical factor to optimize closures and ensure success. The results of this study clearly suggest the use of external fixation can be protective against bladder closure failure. The use of pelvic immobilization, in addition to post-operative lower limb immobilization should be strongly considered.

A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.