De novo variants identified by trio whole exome sequencing of bladder exstrophy epispadias complex.

Bladder exstrophy epispadias complex (BEEC) encompasses a spectrum of conditions ranging from mild epispadias to the most severe form: omphalocele-bladder exstrophy-imperforate anus-spinal defects (OEIS). BEEC involves abnormalities related to anatomical structures that are proposed to have a similar underlying etiology and pathogenesis. In general, BEEC, is considered to arise from a sequence of events in embryonic development and is believed to be a multi-etiological disease with contributions from genetic and environmental factors. Several genes have been implicated and mouse models have been generated, including a knockout model of p63, which is involved in the synthesis of stratified epithelium. Mice lacking p63 have undifferentiated ventral urothelium. MNX1 has also been implicated. In addition, cigarette smoking, diazepam and clomid have been implied as environmental factors due to their relative association. By in large, the etiology and pathogenesis of human BEEC is unknown. We performed de novo analysis of whole exome sequencing (WES) of germline samples from 31 unrelated trios where the probands have a diagnosis of BEEC syndrome. We also evaluated the DECIPHER database to identify copy number variants (CNVs) in genes in individuals with the search terms "bladder exstrophy" in an attempt to identify additional candidate genes within these regions. Several de novo variants were identified; however, a candidate gene is still unclear. This data further supports the multi-etiological nature of BEEC.

["Epidemiology, diagnosis, treatment and follow-up of the bladder exstrophy-epispadias complex"]. / "The making of " ­ die neue S3-Leitlinie "Epidemiologie, Diagnostik, Therapie und Nachsorge des Blasenekstrophie-Epispadie Komplexes".

The development of the new S3 guideline "Epidemiology, diagnosis, treatment and follow-up of the bladder exstrophy-epispadias complex" was funded by the German Innovation Fund of the Federal Joint Committee (G-BA). Despite the relatively low level of evidence of the identified literature, a systematic approach and consistent evaluation of the literature enabled the formulation of a large number of evidence-based recommendations across a variety of topics. In addition, a patient guideline is under development in order to disseminate the guideline recommendations and to enhance self-management and understanding among patients and their relatives. A needs analysis had been carried out in order to adequately assess the topics that are most important for patients and relatives. Upon completion of the German guideline, an English translation in cooperation with the e­UROGEN network is planned.

Ensuring our exstrophy-epispadias complex patients and families thrive.

Individuals with bladder exstrophy-epispadias complex (EEC) need long-term integrated medical/surgical and psychosocial care. These individuals are at risk for medical and surgical complications and experience social and psychological obstacles related to their genitourinary anomaly. This care needs to be accessible, comprehensive, and coordinated. Multiple surgical interventions, reoccurring hospitalizations, urinary and fecal incontinence, extensive treatment regimens for continent diversions, genital differences, and sexual health implications affect the quality of life for the EEC patient. Interventions must include psychosocial support, medical literacy initiatives, behavioral health services, school and educational consultation, peer-to-peer opportunities, referrals to disease-specific camps, mitigation of adverse childhood events (ACEs), formal transition of care to adult providers, family and teen advisory opportunities, and clinical care coordination. The priority of long-term kidney health will necessitate strong collaboration among urology and nephrology teams. Given the rarity of these conditions, multi-center and global efforts are paramount in the trajectory of improving care for the EEC population. To achieve the highest standards of care and ensure that individuals with EEC can thrive in their environment, multidisciplinary and integrated medical/surgical and psychosocial services are imperative.

Prenatal Presentation of a Covered Cloacal Exstrophy Variant; Early Diagnostic Challenges Within the Broad Spectrum of the Exstrophy-Epispadias Complex.

There is a broad range of variant phenotypes that can occur within the bladder exstrophy and epispadias complex spectrum. Accurate prenatal detection helps prepare families and to coordinate subspecialty resources. Here, we present the case of a patient with prenatally diagnosed patient with covered cloacal exstrophy variant along with four additional cases illustrating the nonlinear spectrum from isolated epispadias to cloacal exstrophy. Given the rarity of these variants overall and of each subtype within the spectrum, there is a need for long-term multi-institutional outcomes data to improve detection, characterization, and prognostication for these patients.

Long-Term Management of Problems in Cloacal Exstrophy: A Single-Institution Review.

INTRODUCTION: Cloacal exstrophy (CE) is the most severe malformation of the exstrophy-epispadias complex. This study aims to discuss long-term sequela in a single major institution with a high volume of CE patients. MATERIALS AND METHODS: A prospectively maintained database of 1490 patients on the exstrophy epispadias spectrum (145 cloacal exstrophy) from 1974 to 2023. The patient database was reviewed for CE patients >10 years of age for genitourinary, gastrointestinal, orthopedic, and psychosocial outcomes. RESULTS: A total of 63 patients (43.4%) with ≥10 years of follow up were included for analysis. Thirty-nine (61.9%) patients were 18 years or older. Twenty-two (34.9%) patients were female and 39 (61.9%) male, 14 of whom were gender converted at birth. Two female patients conceived naturally and delivered via cesarean section. No male born CE patients had biological children. Catheterizable channels were common (45/63, 71.4%) and most (88.9%) were continent. Gastrointestinal diversion was managed mostly by colostomy (37/63, 58.7%). Three out of five (60.0%) patients who underwent PSARP were continent of stool. Twenty-two (34.9%) patients were wheelchair-bound. Psychosocial diagnoses included 52.4% (33/63) patients with anxiety/depression and 27.0% with chronic pain. Out of 56 patients evaluated by physical therapy, 75% were independent in ADL performance. Of patients older than 18, 79.5% (31/39) had attended college and 82.1% (32/39) were gainfully employed. CONCLUSION: Advances in critical care, nutrition, gastrointestinal, orthopedic, and urologic management have resulted in survival rates approaching 100% among patients with CE. While these children face long-term sequela spanning various organ systems, many lead independent and fully-functional lives. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level IV.

Urethro-urethrostomy for urethral duplication (Type IIA1) in a 3-years-old boy: Surgical approach.

INTRODUCTION: To report a novel maneuver of end-to-side urethro-urethrostomy for managing Type IIA1 urethral duplication (UD). MATERIALS AND METHODS: A 3-years-old boy was referred to our institute for abnormal appearance of genitalia. Physical examination revealed an epispadiac meatus on the dorsum of the penile shaft, in addition to the orthotopic meatus at the tip of glans. He can void through both urethrae with continence (grade I). Voiding cystourethrography and the cystoscopy confirmed the Type IIA1 UD with two urethrae arising independently from the bladder neck. A novel maneuver of end-to-side urethro-urethrostomy transferring the dorsal urethra through the corpus cavernosa and anastomosing it to the posterior wall of the ventral urethra was successfully performed. RESULTS: The urethral catheter was removed 2 weeks postoperatively. Neither urethral stricture nor fistula was noticed. After 1 year of followed-up, the boy can void fluently with continence (grade I). The Qmax was 10.4 ml/s. CONCLUSION: Our maneuver of end-to-side urethro-urethrostomy for managing Type IIA1 UD was safe and effective, especially for the continent cases with the ectopic meatus on the penile shaft.

An observational study on the sexual, genital and fertility outcomes in bladder exstrophy and epispadias patients.

INTRODUCTION: Bladder exstrophy and epispadias complex (BEEC) is a spectrum of congenital malformations ranging from an isolated epispadias to a full exstrophy. It is an uncommon disease and little is known on how patients cope with its implications later in life. OBJECTIVE: The goal of this study is to assess the sexual, continence and fertility outcomes of BEEC patients, who had reconstructive bladder surgery during childhood. Considering the sensitive nature of these topics, they are not easily spoken about in the doctor's office. Our aim is to shed some light on possible points of improvement in follow-up. STUDY DESIGN: 63 patients between 18 and 45 years old were sent an electronic questionnaire based on previous existing standardized questionnaires. They were asked about sexual and psychosexual wellbeing, urinary incontinence and fertility. Data from their medical files (medical history on previous surgeries). and questionnaire answers are linked through an anonymous subject number and put into an Excel file for descriptive representation. RESULTS: 22 men and 8 women filled in the questionnaire. All but 2 are sexually active. Reasons to avoid sexual activity are equally divided as BEEC-related and non-BEEC-related. Sexual satisfaction is lower in the male group due to problems with erection, ejaculation, condom usage and embarrassment about physical appearance. In females problems concerning pain and reaching orgasm are mentioned. 30% report depressive feelings. There is a clear correlation between number of reconstructive surgeries and sexual satisfaction. 90% of patients urinate via catheterization, mostly through a Mitrofanoff connection. This leads to complications such as foul odors, infection, embarrassment and sexual dysfunction. 8 out of 13 men conceived a child (with the use of their own sperm), 2 out of 4 women did. DISCUSSION: A strength of this study is the use of standardized questionnaires which allow comparison to a control patient group. Our study is one of the first to show how patients cope with the challenges of BEEC by the use of open questions. We see an overall high quality of life yet an important impact on mental health. CONCLUSION: BEEC is associated with many challenges in the adult life of patients. A more holistic and interdisciplinary approach is needed to include sensitive topics in long term follow-up.

Course of an unplanned and unexpected pregnancy in a 39 year-old patient with Complex bladder extrophy: a case report.

BACKGROUND: With improved operative techniques pregnancy rates have been rising in patients with anomalies of the extrophy-epispadias-complex, including also female patients with bladder extrophy. Specific risks around pregnancy need to be addressed sufficiently beforehand. CASE PRESENTATION: An unplanned pregnancy was detected at 34 weeks in a 39-year old White female patient with former complex bladder extrophy. Decades after her operation she had not received any follow-up medical care and believed to be unable to conceive due to her anomaly. Thus no contraceptive matters were taken. The patient had lived in a stable relationship with regular sexual intercourse for many years. Until 34 weeks the pregnancy was uncomplicated, but then uterine prolapse and signs of beginning pre-eclampsia appeared, and a healthy girl was born with cesarean section. CONCLUSION: As patients with bladder extrophy and other anomalies from the extrophy-epispadias-complex reach adolescence/adulthood, they need continuous medical follow-up and transition of care to adult surgery and gynecology in order to address specific aspects of sexual health, reproduction, contraception, and also cancer screening. In the presented case lack of transition of care resulted in an unplanned and complicated pregnancy.

Multi-staged vs Single-staged Pelvic Osteotomy in the Modern Treatment of Cloacal Exstrophy: Bridging the Gap.

PURPOSE: Staged pelvic osteotomy has been shown in the past to be an effective tool in the closure of the extreme pubic diastasis of cloacal exstrophy. The authors sought to compare orthopedic complications between non-staged pelvic osteotomies and staged pelvic osteotomies in cloacal exstrophy. METHODS: A prospectively maintained exstrophy-epispadias complex database of 1510 patients was reviewed for cloacal exstrophy bladder closure events performed with osteotomy at the authors' institution. Bladder closure failure was defined as any fascial dehiscence, bladder prolapse, or vesicocutaneous fistula within one year of closure. There was a total of 172 cloacal exstrophy and cloacal exstrophy variant patients within the database and only closures at the authors' institution were included. RESULTS: 64 closure events fitting the inclusion criteria were identified in 61 unique patients. Staged osteotomy was performed in 42 closure events and non-staged in 22 closures. Complications occurred in 46/64 closure events, with 16 grade III/IV complications. There were no associations between staged osteotomy and overall complication or grade III/IV complications (p = 0.6344 and p = 0.1286, respectively). Of the 46 total complications, 12 were orthopedic complications with 6 complications being grade III/IV. Staged osteotomy closure events experienced 10/42 orthopedic complications while non-staged osteotomy closures experienced 2/22 orthopedic complications, however this did not reach significance (p = 0.1519). Of the 64 closure events, 57 resulted in successful closure with 6 failures and one closure with planned cystectomy. CONCLUSION: This study confirms, in a larger series, superior outcomes when using staged pelvic osteotomy in cloacal exstrophy bladder closure. Staged osteotomy was shown to be a safe alternative to non-staged osteotomy that can decrease the risk of closure failure in this group. Staged pelvic osteotomy should be considered in all patients undergoing cloacal exstrophy bladder closure. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.

Three-dimensional Computed Tomography Scan of the Pelvic Bone in Isolated Epispadias: Analysis Before Surgical Correction.

OBJECTIVE: To determine intrapelvic angles and distances in pure epispadias patients and compare them to normal values. METHODS: Using three-dimensional computed tomography, 17 intrapelvic dimensions (8 angles and 9 distances) were measured in 26 patients with pure epispadias (21 boys and 5 girls). These values were compared to normal values obtained from 6 patients (5 boys and 1 girl) who underwent either pelvic or abdominopelvic computed tomography for purposes unrelated to their bony pelvis. RESULTS: Significant differences were observed in five angles (sacroiliac joint angle, S1 tilt angle, sacral curvature, superior-inferior rotation of the pelvis, and pubococcygeal angle; P-value=.016, .044, .011, .020, and .001, respectively); these show less sacral rotation toward the axial plane, more sacral curvature, inferior rotation of the pelvis, and sacroiliac joints' rotation toward the coronal plane in epispadias compared to controls. Also, two distances (pubic diastasis and anterior segment length of the pelvis; P-value=.002 and .012, respectively) had significant differences, showing wider pubic diastasis and shorter anterior segment in epispadias. However, the differences between other intrapelvic angles and distances were not statistically significant between the two groups. CONCLUSION: In addition to the explanations hypothesized for the embryology of the exstrophy-epispadias complex, there can be other etiologies for both epispadias and bladder exstrophy to explain the differences between bony anatomies of the pelvis in these patients.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Classical bladder exstrophy in an adolescent: A case report on management, challenges and outcome.

Classical bladder exstrophy is a congenital anomaly whose management and outcome has advanced over years. Management and outcome are better when management starts at the newborn period. This was the management of a neglected bladder exstrophy in a male presenting at 16 years of age. We report our challenges, management and outcome to highlight the rarity of this presentation, and the adaptation to the usual protocol of care. The patient presented at 16 years of age with classic bladder exstrophy. The bladder plate was contracted and had cystitis. The patient had a modification of complete primary repair of exstrophy (CPRE) with bilateral pelvic osteotomy stabilised with a 7-hole plate and 4 screws, then bladder neck reconstruction + bladder augmentation + cross-trigonal neocystoureterostomy in a 12-h procedure. He had surgical site infection, superficial wound breakdown and vesicocutaneous fistula that all healed with dressing and prolonged suprapubic cystostomy drainage. He achieved some degree of urinary continence and ability to void, though he still has stress incontinence and frequency at 6 months of follow-up. He has a micturition interval of 60-120 min, and is expected to improve. Presentation and repair of classic bladder exstrophy in the adolescent is very rare in the literature and therefore no known standard of care. This report adds to the body of knowledge. Again, this experience lends credence to the proponents of CPRE in reducing the number of procedures required to treat exstrophy.

Exstrophy-Epispadias Complex.

Exstrophy-epispadias complex encompasses a spectrum of disorders with lower abdominal midline malformations, including epispadias, bladder exstrophy, and cloacal exstrophy, also known as Omphalocele-Exstrophy-Imperforate Anus-Spinal Anomalies Complex. In this review, the authors discuss the epidemiology, embryologic cause, prenatal findings, phenotypic characteristics, and management strategies of these 3 conditions. The primary focus is to summarize outcomes pertaining to each condition.

Exstrophic bladder duplication in the sagittal plane: Surgical management of a rare case.

INTRODUCTION: The bladder-Exstrophy-Epispadias complex (BEEC) contains a wide spectrum of congenital malformations. A treatment naïve refugee was referred to our center with what was identified as BEEC. MATERIALS AND METHODS: A 27-year-old female patient was referred for total incontinence since birth by the general practitioner from the refugee center. An exstrophic bladder with blind ending ureteral orifices and a second non-exstrophic bladder with two orthotopic ureters was identified, demonstrating the bladder duplication in the sagittal plane. Laparotomy was performed, dissecting the exstrophic bladder plate caudally and using it as a ventral onlay to augment the non-exstrophic bladder. A Mitchell-type bladder neck reconstruction was performed with an autologous fascia sling around the bladder neck to obtain continence. As the patient had never voluntarily voided, chances of spontaneous voiding after surgery were low. Therefore creation of a continent Mitrofanoff-type vesicostomy was additionally realized and genital reconstruction was achieved. RESULTS: 12 months post operatively, the patient was completely continent, had a bladder capacity of 250 ml, and performed self-catheterization 5 times a day. No post-operative complications were observed. CONCLUSION: Admission of political refugees can implicate challenging surgeries for congenital malformations in adults, such as BEEC. This demonstrates the importance of multidisciplinary transitional care.

Marked Metabolic Acidosis Due to a Transverse Stoma after Urethroplasty for Congenital Epispadias.

A 58-year-old woman was admitted to our hospital. At 10 years old, she had undergone bilateral uretero-sigmoid anastomosis for congenital epispadias, and at 57 years old, she had received transverse colostomy. Biochemical tests showed marked metabolic acidosis. Computed tomography showed urine stagnation in the sigmoid colon, leading to a diagnosis of metabolic acidosis associated with transverse stoma after bilateral uretero-sigmoid anastomosis. Her bone mineral density was below normal, and the bone metabolic marker levels were high, indicating high-turnover osteoporosis. Both metabolic acidosis and bone metabolism were stabilized by treatment with a transanal urinary catheter, sodium bicarbonate, and vitamin D.

A Single-Institutional Experience With Prenatal Diagnosis of Cloacal Exstrophy: Room for Improvement.

INTRODUCTION: A single institutional study characterizes the rate of prenatal diagnosis of cloacal exstrophy (CE) and examines its role on successful primary closures. MATERIALS AND METHODS: An institutional database of 1485 exstrophy-epispadias patients was reviewed retrospectively for CE patients with confirmed presence/absence of prenatal diagnostics, primary exstrophy closure since 2000, institution of closure, and at least 1 year of follow up following closure. RESULTS: The cohort included 56 domestic patients and 9 international patients. Overall, 78.6% (n = 44) of domestic patients were prenatally diagnosed while 21.4% (n = 12) were diagnosed postnatally. A positive trend was observed in the rate of prenatal diagnosis across the study period, 56.3%, 84.2%, 88.9% respectively (p = 0.025). Confirmatory fMRI was obtained in 40.9% (n = 18) of prenatally diagnosed cases. Patients diagnosed prenatally were found to be more likely to undergo treatment at exstrophy centers of excellence (72.1% v 33.3%, p = 0.020). Prenatal diagnosis was not predictive of increased rate of successful primary closure (75.6% vs 75.0%; p = 1.00; OR: 1.03, 95% CI: 0.23-4.58). Primary closures undertaken at exstrophy centers of excellence were significantly more likely to be successful compared to outside hospitals (90.9% v 50.0%, p = 0.002). CONCLUSIONS: The rate of prenatal diagnosis of CE in patients referred for management to a high-volume exstrophy center is improving. Despite this improvement, patients continue to be missed in the prenatal period. While prenatal diagnosis offers the ideal opportunity to educate, counsel, and prepare expectant families, patients diagnosed at birth are not disadvantaged in their ability to receive a successful primary closure. Further research should investigate the benefit of patient referral to high-volume exstrophy centers of care to ensure optimal care and outcomes.

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.

Spectrum and classification of megameatus anomalies.

OBJECTIVE: To define and classify megameatus anomalies, the parameters of a considerable number of cases were investigated and compared with those of normal children. METHODS: A total of 1150 normal babies were examined during routine nonmedical circumcision, and another 750 boys referred with hypospadias were examined during the previous 3 years. All patients were evaluated and assessed for the size, location, and configuration of the urinary meatus, and penile length and girth were measured. Children with normal size and location of the meatus were considered control group A, and 42 cases of different forms of megameatus were considered group B. Other penoscrotal, urinary, and general anomalies were examined and investigated accordingly. All data were analyzed by the SPSS 9.0.1 statistical package and compared by paired t tests. RESULTS: Forty-two uncircumcised patients aged from 1 month to 4 years (mean 18 months) were diagnosed with a urinary meatus that engrossed the whole ventral or dorsal aspects of the glans, exceeding half the width of the glans or penile girth with the complete vanishing of the glans closure in most cases. Megameatus is usually associated with the abnormal meatal position as hypospadiac, orthotopic, or epispadic. Additionally, megameatus may be associated with a normally intact or deficient prepuce. Consequently, we had four categories of megameatus, and the intact prepuce orthotopic megameatus subcategory has not been described before. Megameatus was also detected with deficient prepuce, and this was considered a hypospadiac variant. CONCLUSION: Megameatus is diagnosed precisely with penile biometry and is classified into 4 groups: hypospadiac, epispadic, and orthotopic or central, either with or without intact prepuce. This classification is applicable for expansion to other centers.

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

OBJECTIVE: To investigate management trends in a single institution with a large referral population in classic bladder exstrophy (CBE) over the past twenty years. METHODS: 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. RESULTS: 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 = .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). CONCLUSION: 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.