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Purpose: We sought to determine if the addition of liposomal bupivacaine to bupivacaine hydrochloride improves opioid-free rate and postoperative pain scores among children undergoing ambulatory urologic surgery., Materials and Methods: A prospective, phase 3, single-blinded, single-center randomized trial with superiority design was conducted in children 6 to 18 years undergoing ambulatory urologic procedures between October 2021 and April 2023. Patients were randomized 1:1 to receive dorsal penile nerve block (penile procedures) or incisional infiltration with spermatic cord block (inguinal/scrotal procedures) with weight-based liposomal bupivacaine plus bupivacaine hydrochloride or bupivacaine hydrochloride alone. The primary outcome was opioid-free rate at 48 hours. Secondary outcomes included parents' postoperative pain measure scores, numerical pain scale scores, and weight-based opioid utilization at 48 hours and 10 to 14 days., Results: We randomized 104 participants, with > 98% (102/104) with complete follow-up data at 48 hours and 10 to 14 days. At interim analysis, there was no significant difference in opioid-free rate at 48 hours between arms (60% in the intervention vs 62% in the control group; estimated difference in proportion -1.9% [95% CI, -20%-16%]; P = .8). We observed no increased odds of patients being opioid-free at 48 hours with the intervention compared to the control group (OR 0.96 [95% CI 0.41-2.3]; P = .9). The trial met the predetermined futility threshold for early stopping. There was no difference in parents' postoperative pain measure scores, numerical pain scale scores, or opioid utilization at 48 hours or 10 to 14 days. No difference in adverse events was observed., Conclusions: The addition of liposomal bupivacaine to bupivacaine hydrochloride did not significantly improve opioid-sparing effect or postoperative pain compared with bupivacaine hydrochloride alone among children ≥ 6 years undergoing ambulatory urologic surgery.

Purpose: The authors examined the urothelium of exstrophy-epispadias complex spectrum patients for histological differences and expression of terminal markers of urothelial differentiation., Materials and Methods: Between 2012 and 2017 bladder biopsies were obtained from 69 pediatric exstrophy-epispadias complex patients. These specimens were compared to bladder specimens from normal controls. All bladder specimens underwent histological assessment followed by immunohistochemical staining for uroplakin-II and p63. Expression levels of uroplakin-II and p63 were then assessed by a blinded pathologist., Results: Forty-three classic bladder exstrophy biopsies were obtained (10 newborn closures, 22 delayed closures, and 11 repeat closures). Additional biopsies from 18 cloacal exstrophy patients and 8 epispadias patients were also evaluated. These specimens were compared to 8 normal control bladder specimens. Overall, uroplakin-II expression was lower in exstrophy-epispadias complex patients compared to controls (p <0.0001). Among classic bladder exstrophy patients, there was reduced expression of uroplakin-II in the delayed and repeat closures in comparison to newborn closures (p=0.045). Expression of p63 was lower in patients with exstrophy-epispadias complex compared to controls (p <0.0001). Expression of p63 was similar among classic bladder exstrophy patients closed as newborns when compared to delayed or repeat closures. Classic bladder exstrophy patients had a higher rate of squamous metaplasia when compared to controls (p=0.044). Additionally, there was a higher rate of squamous metaplasia in the patients undergoing delayed closure in comparison to those closed in the newborn period (p <0.001)., Conclusions: The urothelium in the exstrophy-epispadias complex bladder is strikingly different than that of healthy controls. Uroplakin-II expression is greatly reduced in exstrophy-epispadias complex bladders and is influenced by the timing of bladder closure. Reduced uroplakin-II expression and increased rates of squamous metaplasia in exstrophy-epispadias complex patients undergoing delayed closure suggests that exposure of the urothelium may induce these changes. These findings shed light on the molecular changes in exstrophy-epispadias complex bladders and may have implications on the appropriate timing of primary bladder closure, as those closed in the newborn period appear to have a greater potential for growth and differentiation.

Purpose: Male patients with exstrophy-epispadias complex have a congenitally short penis. Adolescent and adult patients often desire penile reconstruction to enable penetrative intercourse. When penile lengthening using local tissue and/or skin graft is unsuitable, phalloplasty is performed. We provide updated experiences using radial forearm free flap and pedicled anterolateral thigh flap phalloplasty techniques over a 6-year period in exstrophy-epispadias complex patients., Materials and Methods: Consecutive patients who underwent radial forearm free flap or pedicled anterolateral thigh flap phalloplasty between 2013 and 2019 were reviewed. A total of 11 patients were identified, including 8 with classic bladder exstrophy and 3 with cloacal exstrophy. In each case, flap dimensions, donor and recipient vessels and nerves, complications, outcomes and subsequent surgical procedures are reported., Results: A radial forearm free flap was performed in 6 patients and a pedicled anterolateral thigh flap in 5. Flap survival was observed in all cases and 5 patients subsequently received an inflatable penile prosthesis. Among patients undergoing a pedicled anterolateral thigh flap, there was 1 mortality from acute pulmonary embolism, and the other 4 required at least 1 debulking procedure., Conclusions: Phalloplasty is an important procedure in patients with exstrophy-epispadias complex with severe penile inadequacy. Both techniques have favorable long-term outcomes, although the pedicled anterolateral thigh flap frequently requires a later debulking procedure. The radial forearm free flap is preferred but if the radial forearm is overly thin and the risk of inflatable penile prosthesis extrusion is high, the pedicled anterolateral thigh flap is an acceptable alternative.

Purpose: We investigated surgical approaches to urinary incontinence and long-term continence outcomes after successful bladder reconstruction in a heterogeneous patient population with classic bladder exstrophy. We hypothesized that while most patients will achieve urinary continence after surgery, only a select group will void volitionally per urethra., Materials and Methods: An institutional database of 1,323 patients with exstrophy-epispadias complex was reviewed for patients with classic bladder exstrophy who underwent successful bladder closure and a subsequent continence procedure between 1975 and 2017. Procedures included bladder neck reconstruction, bladder neck reconstruction with augmentation cystoplasty or continent catheterizable stoma, and bladder neck closure with continent catheterizable stoma. Cloacal exstrophy, epispadias and variant exstrophy cases were excluded from analysis. Continence at last followup was defined as a dry interval of 3 or more hours without nighttime leakage. Those patients with more than 3 months of followup were assessed., Results: Overall 432 patients underwent successful bladder closure (primary 71.5%, repeat 28.5%) and a urinary continence procedure. At last followup 162 (37%) underwent bladder neck reconstruction, 76 (18%) underwent bladder neck reconstruction with augmentation cystoplasty or continent catheterizable stoma, 173 (40%) underwent bladder neck closure with continent catheterizable stoma and 18 underwent other procedures. Median followup from the first continence procedure was 7.2 years (IQR 2.3-13.7). Continence was assessed in 350 patients. After isolated bladder neck reconstruction 91 of 142 patients were continent (64%, 95% CI 56-72). After bladder neck closure with continent catheterizable stoma 124 of 133 patients evaluated were continent (93%, 95% CI 87-97)., Conclusions: Most patients with classic bladder exstrophy require multiple reconstructive procedures to achieve continence. Only about 25% of patients are expected to void normally per urethra without reliance on catheterization or urinary diversion.

Purpose: We determined the safety and efficacy of intraoperative magnetic resonance imaging guided surgical reconstruction of bladder exstrophy for the identification of the urogenital diaphragm fibers and the thickened muscular attachments between the posterior urethra, bladder plate and pubic rami., Materials and Methods: Institutional review board and U.S. Food and Drug Administration approval was obtained for the use of Brainlab (Munich, Germany) intraoperative magnetic resonance imaging guided navigation of the pelvic floor anatomy during closure of classic bladder exstrophy and cloacal exstrophy at our institution. Preoperative pelvic 3-dimensional magnetic resonance imaging was obtained 1 day before closure in patients undergoing pelvic osteotomies. Intraoperative registration was performed after preoperative planning with a pediatric radiologist using 5 anatomical landmarks immediately before initiation of surgery. Accuracy of pelvic anatomy identification was assessed by 2 pediatric urological surgeons and 1 pediatric radiologist., Results: In 43 patients with classic bladder exstrophy and 4 patients with cloacal exstrophy closed at our institution, Brainlab technology was used successfully to navigate and guide the dissection of the pelvic floor intraoperatively. In all patients there was 100% accuracy in the correlation of gross anatomical landmarks with 3-dimensional magnetic resonance imaging identified landmarks intraoperatively, and all patients had successful closure without any major complications., Conclusions: Brainlab intraoperative 3-dimensional magnetic resonance imaging guided pelvic floor navigation and dissection is an effective way to accurately identify pelvic anatomy during classic bladder exstrophy and cloacal exstrophy closure. This technology offers a unique opportunity for surgical skill education in this complex reconstructive operation.

Purpose: We used magnetic resonance imaging to define the innate pelvic neurovascular course and prostatic anatomy in infants with classic bladder exstrophy before the pelvis was altered by surgery., Materials and Methods: Pelvic magnetic resonance imaging was performed in male infants with classic bladder exstrophy and compared to a group of age matched controls. Data collected included prostatic dimensions as well as course of the prostatic artery, periprostatic vessels and pudendal neurovasculature., Results: The prostate was larger in the transverse (p <0.001) and anteroposterior (p <0.001) dimensions in patients with classic bladder exstrophy compared to those with normal prostates but was smaller in the craniocaudal dimension (p <0.001). This finding resulted in a larger calculated prostate volume in patients with classic bladder exstrophy compared to controls (p = 0.015). The pelvic vasculature and prostatic artery followed a similar course in patients with classic bladder exstrophy and controls. Relative to each other, the lateral to medial course of the prostatic arteries in males with classic bladder exstrophy was less pronounced than in normal males. A similar externally rotated pattern was seen when both sides of the pudendal vasculature were compared in males with classic bladder exstrophy., Conclusions: The prostate in infants with classic bladder exstrophy has a consistent configuration and dimensions that differ from those in normal infants. When both sides are compared, the periprostatic vasculature and penile sensory neurovascular bundles are externally rotated in infants with classic bladder exstrophy. However, these components course along the same landmarks as in normal patients., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Understanding the distinct female anatomy in classic bladder exstrophy is crucial for optimal reconstructive and functional outcomes. We present novel quantitative anatomical data in females with classic bladder exstrophy before primary closure., Materials and Methods: 3-Dimensional reconstruction was performed in patients undergoing pelvic magnetic resonance imaging, and pelvic anatomy was characterized, including measurements of the vagina, cervix and erectile bodies., Results: We examined magnetic resonance imaging of 5 females (mean age 5.5 months) with classic bladder exstrophy and 4 age matched controls (mean age 5.8 months). Mean distance between the anal verge and vaginal introitus was greater in patients with classic bladder exstrophy (2.43 cm) than in controls (1.62 cm). Mean total vaginal length in patients with classic bladder exstrophy was half that of controls (1.64 cm vs 3.39 cm). All 4 controls had posterior facing cervical ora, while 4 of 5 females with exstrophy had anterior facing cervical ora located in the anterior vaginal wall. Lateral deviation of the cervical ora was also seen in all 5 patients with classic bladder exstrophy but in only 1 control. Clitoral body length was comparable in both groups (26.2 mm and 28.0 mm). However, the anterior cavernosa-to-posterior (pelvic rami associated) cavernosa ratio was much greater in patients with classic bladder exstrophy (6.4) compared to controls (2.5)., Conclusions: This study uncovers the uniquely novel finding that contrary to their male counterparts, females with classic bladder exstrophy have the majority of the clitoral body anterior to the pelvic attachment. This discovery has surgical and embryological implications., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Successful primary bladder exstrophy closure provides the best opportunity for patients to achieve a functional closure and urinary continence regardless of the method of repair. Use of osteotomy during initial closure has significantly improved success rates. However, failures can still occur. We identify factors that contribute to a failed primary exstrophy closure with osteotomy., Materials and Methods: We reviewed a prospectively maintained institutional database for classic bladder exstrophy cases primarily closed with osteotomy at our institution or referred after primary closure between 1990 and 2015. Data were collected regarding patient gender, closure, osteotomy, immobilization, orthopedics and perioperative pain control. Univariate and multivariable analyses were performed to determine predictors of failure., Results: A total of 156 patients met inclusion criteria. Overall failure rate was 30% (13% from our institution and 87% from referrals). On multivariable analysis use of Buck traction (OR 0.11, 95% CI 0.02-0.60, p = 0.011) and immobilization time greater than 4 weeks (OR 0.19, 95% CI 0.04-0.86, p = 0.031) had significantly lower odds of failure. Osteotomy performed by general orthopedic surgeons had significantly higher odds of failure (OR 23.47, 95% CI 1.45-379.19, p = 0.027). Type of osteotomy and use of epidural anesthesia did not significantly impact failure rates., Conclusions: Proper immobilization with modified Buck traction and external fixation, immobilization time greater than 4 weeks and undergoing osteotomy performed by a pediatric orthopedic surgeon are crucial factors for successful primary closure with osteotomy., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Complete male epispadias is a rare congenital anomaly characterized by failed closure of the entire penopubic dorsal urethra. Epispadias repair is typically performed during infancy, and resultant genitourinary abnormalities can have a marked impact on adult life. We assess long-term post-reconstruction sexual health and fertility outcomes in adults with complete male epispadias., Materials and Methods: A total of 132 patients 18 years or older with complete male epispadias who had undergone reconstruction were identified from a prospectively maintained, institutionally approved database. Patients who could be contacted were asked to complete a telephone survey regarding sexual function. Reconstructive history and clinical details were obtained by chart/database review., Results: Of 132 patients with complete male epispadias 74 met inclusion criteria and 15 (20%) completed the questionnaire. Seven patients (47%) reported currently being in a relationship. Although 12 patients (80%) reported overall satisfactory sexual intercourse, 11 (73%) admitted to 1 or more problems with sexual function, including abnormal ejaculation (53%), diminished sensation (20%) and difficulty maintaining an erection (20%). When questioned regarding the importance of fertility on a scale of 0 to 5 using a Likert-type item the response of 10 patients (67%) was 4 points or greater. Five patients (33%) reported having impregnated a sexual partner. Although 4 patients (27%) had suspicion of fertility problems, only 2 (13%) reported having abnormal semen analyses., Conclusions: This is one of few studies examining post-reconstruction sexual health and function in adults with complete male epispadias. Although small, our study demonstrates that patients are able to engage in relationships, participate in sexual intercourse and impregnate their partners. These results highlight sexual concerns and outcomes that may be of use when counselling patients with complete male epispadias and their families., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Male patients with bladder and cloacal exstrophy are born with demure genitalia and often desire phalloplasty during late adolescence or early adulthood. Radial forearm free flap phalloplasty was used successfully for congenital aphallia in a few small series. We present a series of patients treated with phalloplasty using a radial forearm free flap after the repair of bladder and cloacal exstrophy., Materials and Methods: We reviewed the records of 10 patients who underwent radial forearm free flap phalloplasty between 2007 and 2012. Indications for phalloplasty were classic bladder exstrophy in 8 cases and cloacal exstrophy in 2. Nine patients underwent prior urinary diversion and 1 underwent urethroplasty at phalloplasty. In each case we reviewed the details of prior exstrophy repair, flap size, donor and recipient vessels, complications, need for subsequent surgeries and self-reported sensation., Results: The graft survived in all 10 patients. Short-term complications requiring surgical intervention developed in 2 patients. Five patients subsequently underwent placement of a penile prosthesis and 2 devices were removed secondary to erosion. All 10 patients reported protective sensation and erogenous sensation with ability to achieve orgasm at last followup., Conclusions: Radial forearm free flap phalloplasty results in a sensate, cosmetic neophallus. No patient had long-term complications related to phalloplasty but complications related to penile prostheses continue to be a challenging aspect of phalloplasty. The long-term results of the forearm free flap are encouraging in this series of patients with bladder and cloacal exstrophy who desired phalloplasty., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Complete female epispadias, which occurs much more rarely than classic bladder exstrophy in females, is thought to have a more benign clinical course. We hypothesized that patients with complete female epispadias are more likely to have a larger bladder capacity and achieve voiding continence than females with classic bladder exstrophy., Materials and Methods: After obtaining institutional review board approval, females with complete female epispadias or classic bladder exstrophy were identified from an institutionally approved prospective database. We retrospectively reviewed the charts of 22 patients with complete female epispadias and 23 with female classic bladder exstrophy, including 3 with delayed primary closure., Results: Patients with complete female epispadias presented later and underwent the first reconstructive procedure at an older age than patients with classic bladder exstrophy. Patients with complete female epispadias had lower initial and final age adjusted bladder capacity than those with classic bladder exstrophy but the bladder growth rate did not differ between the groups. When patients with complete female epispadias were stratified by age at initial reconstruction, there was no difference in final age adjusted bladder capacity or the bladder growth rate. There was also no statistical difference between the groups in the number of surgeries, continence rate from initial reconstruction, bladder neck reconstruction success or need for a continent stoma., Conclusions: This study suggests that females with classic bladder exstrophy who undergo successful primary closure have higher initial and final age adjusted bladder capacity than females with complete female epispadias but with a similar growth rate. This may reflect the creation of outlet resistance at a younger age than in those with complete female epispadias. However, no difference was identified between patients with complete female epispadias who initially underwent repair before vs after age 1 year. Patients with complete female epispadias undergo procedures to achieve continence that are similar to those in patients with classic bladder exstrophy., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Late referrals or unsuitable bladder templates often require delayed primary repair of bladder exstrophy. We investigated longitudinal bladder growth rates and eventual outcomes following this approach., Materials and Methods: After institutional review board approval, we reviewed the medical records of patients with classic bladder exstrophy who underwent neonatal or delayed (more than 30 days) primary closure at our institution between 1970 and 2006. Clinical characteristics and annual cystographic bladder capacity before the continence procedure were compared. Failed primary exstrophy repairs were excluded., Results: A total of 33 patients with available bladder capacity measurements underwent delayed exstrophy closure due to small bladder template in 18 (88% male) and late referral in 15 (80% male) at respective median ages of 305 days (range 86 to 981) and 172 days (31 to 676). They were compared to 82 patients (71% male) undergoing neonatal closure at a median of 2 days of life (range 0 to 27). Pelvic osteotomy was performed in 32 of 33 delayed closures. Longitudinal analysis of the bladder capacities demonstrated that, compared to neonatally closed cases, bladder capacities were on average 36 ml smaller in those with delayed repair due to small templates (p = 0.01) and 29 ml smaller in those with late referrals (p = 0.13). However, the rate of bladder growth did not differ significantly among the 3 groups., Conclusions: Delayed primary repair of exstrophy does not compromise the rate of bladder growth. However, children born with smaller templates will have overall smaller capacities and are less likely to undergo bladder neck reconstruction., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Bladder exstrophy is a major congenital anomaly involving defects in the genitourinary tract and pelvic musculoskeletal system. It appears intuitive that closure of the pelvic ring using osteotomy would be associated with a decreased risk of pelvic organ prolapse. We investigated whether osteotomy is associated with a decreased risk of pelvic organ prolapse in females with classic bladder exstrophy., Materials and Methods: We searched our institutional review board approved exstrophy database of 1,078 patients and identified 335 females. We excluded patients who were younger than 13 years, had cloacal exstrophy or epispadias and did not have postpubertal imaging for measurement of pubic diastasis available. Our final study population consisted of 67 females. Univariate analysis was performed using t test or rank sum test for continuous variables and chi-square test for categorical variables. Logistic regression was used for multivariate analysis., Results: Median patient age was 23 years (range 13 to 60). A total of 20 patients (29.9%) had pelvic organ prolapse at a median age of 20 years (range 11 to 43). Of the 67 patients 25 (37.3%) had undergone osteotomy at a median age of 6 months (range birth to 10 years). Seven patients had at least 1 pregnancy (range 1 to 3), and 24 patients had undergone vaginoplasty. On univariate analysis only diastasis was associated with pelvic organ prolapse, with smaller diastasis associated with a decreased risk of prolapse. On multivariate analysis including diastasis and osteotomy only diastasis was statistically significant., Conclusions: Osteotomy does not decrease the risk of pelvic organ prolapse in patients with classic bladder exstrophy. Rather, degree of diastasis is significantly associated with pelvic organ prolapse., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We determined health related quality of life as reported by adolescents with bladder exstrophy or epispadias using a validated generic instrument., Materials and Methods: Adolescents age 11 to 18 years with bladder exstrophy or epispadias (57) completed a validated, generic, health related quality of life instrument, the CHQ-CF87 (Child Health Questionnaire-Child Form 87). Urinary incontinence, catheterization status, and medical and surgical history data were also obtained. Mean summary scores and 95% CIs for each subdomain of the CHQ-CF87 were calculated, and descriptively compared to 2 population based samples. In our sample health related quality of life outcomes by continence status were compared using univariate and multivariate analysis. However, this analysis was limited by a small sample size., Results: Mean age of the 49 patients with bladder exstrophy and the 8 with epispadias was 14.3 years, 67% were male and 81% were Caucasian. There were 31 participants who reported incontinence and the median number of lifetime surgeries was 9. The exstrophy population scored well in all subdomains of the instrument when descriptively compared to 2 large samples of adolescent populations. In our sample incontinent patients had lower scores by multivariate analysis in 7 of 10 domains and better scores in 3 of 10 domains, although these differences were not statistically significant., Conclusions: Adolescents with bladder exstrophy and epispadias reported relatively good scores on the CHQ-CF87 when descriptively compared to other reference populations. This finding suggests that these children adapt well to the challenges of their condition. Analysis of the association of incontinence with health related quality of life was limited by the small sample size., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Transforming growth factor-β1 regulates extracellular matrix composition, and impacts function and proliferation in multiple cell types, including bladder smooth muscle cells. In this study we evaluated the response to transforming growth factor-β1 in cultured exstrophy and control bladder smooth muscle cells., Materials and Methods: Primary bladder smooth muscle cell cultures were established from patients with bladder exstrophy or vesicoureteral reflux. Smooth muscle specific α-actin and heavy chain myosin expression was determined using immunohistochemistry. Cell migration, intracellular calcium concentration and proliferation were determined after incubation for 24 to 48 hours in basal media, with or without transforming growth factor-β1 (0.001 to 3 nM) or transforming growth factor-β1 receptor inhibitor SB 431542 (10 μM)., Results: Cultured exstrophy and control smooth muscle cells stained positive for α-actin and heavy chain myosin. Exstrophy smooth muscle cells demonstrated increased migration compared to control smooth muscle cells at baseline (38% vs 20%, p = 0.01). Transforming growth factor-β1 increased control smooth muscle cell migration while SB 431542 decreased exstrophy smooth muscle cell migration. Control cells had a higher intracellular calcium concentration, which decreased significantly when exposed to SB 431542. Transforming growth factor-β1 did not cause significant changes in intracellular calcium concentration. Inhibition of transforming growth factor-β1 receptors decreased proliferation in exstrophy and control smooth muscle cells, but exogenous transforming growth factor-β1 did not impact proliferation., Conclusions: Our results suggest that there are distinct differences in bladder smooth muscle cell function between control and exstrophy cases which persist in culture. Although resting intracellular calcium concentration was higher in control cells, proliferation rates were similar in both cell types, indicating that lower intracellular calcium concentration did not impact growth potential. In contrast, enhanced migration was observed in exstrophy cells, possibly due to excess transforming growth factor-β1 signaling, but seemingly independent of increases in intracellular calcium concentration., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Previous studies have suggested that exstrophic bladder smooth muscle cells grown in culture show contractility similar to that of normal bladder smooth muscle cells. Despite this similar contractility, other cellular characteristics may vary between exstrophic and normal bladder smooth muscle cells., Materials and Methods: Primary cultures of bladder smooth muscle cells were established from patients with bladder exstrophy (14) and vesicoureteral reflux as a control (10). Expression of smooth muscle specific α-actin and heavy chain myosin was determined with immunohistochemistry. Response of smooth muscle cells to high potassium Krebs solution or acetylcholine (0.1 mM) was assessed using a calcium sensitive fluorescent dye. Intracellular calcium concentration was measured after 48 hours in basal media. Cell migration in basal media during 24 hours was determined using transwell assays. Baseline proliferation and response to 10% fetal bovine serum were assessed with bromodeoxyuridine incorporation assays., Results: More than 95% of exstrophy and control smooth muscle cells stained positive for actin and myosin. Functional integrity was verified in each exstrophy and control cell line by response to high potassium Krebs solution or acetylcholine. The intracellular calcium concentration was lower in exstrophy smooth muscle cells than in control smooth muscle cells (71 vs 136 nM, p <0.001). More exstrophy cells migrated than control cells (37% vs 18%, p = 0.004). There was no statistically significant difference in proliferation between exstrophy and control smooth muscle cells in basal or growth media., Conclusions: Cultured exstrophy smooth muscle cells demonstrate some differences in baseline characteristics compared to control cells. Differences in migration and intracellular calcium may have implications for in vivo detrusor function and tissue engineering., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We used 3-dimensional magnetic resonance imaging reconstruction to generate models of the pelvic floor musculature in classic bladder exstrophy, allowing for statistical analysis of changes seen in the anatomy after primary closure., Materials and Methods: Patients with classic bladder exstrophy underwent pelvic magnetic resonance imaging before and after primary closure. Contours of the levator ani were mapped and measured in 3-dimensional space. In addition, 2-dimensional angles and measurements were used to make a quantitative and qualitative analysis of the pelvic floor before and after closure., Results: A total of 19 cases of classic bladder exstrophy were included in the study, with 12 closed as newborns without osteotomy and 7 closed later with osteotomy. In both groups the pre-closure exstrophy pelvic floor in the axial plane was box-like and after closure it had a more inward rotation. The steepness and angulation of the levator ani muscle remained relatively unchanged in both groups. The levator ani muscle group, with and without osteotomy, was redistributed into the anterior compartment of the pelvis after closure. Postoperatively a successfully closed exstrophy had the bladder positioned deeply within the pelvis. After closure the levator ani muscle regained the expected smooth contoured shape., Conclusions: Primary closure of bladder exstrophy 1) reshapes the pelvis from a box-like configuration to a more inwardly rotated hammock, 2) redistributes a significant portion of the levator ani muscle into the anterior compartment and 3) facilitates a smooth uniform contouring to the pelvic floor. Closing the bony pelvic ring by pubic reapproximation in the newborn or by osteotomy in an infant produces similar changes in the pelvic floor., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Failed initial bladder exstrophy closure may hinder the natural course of bladder growth compared to successful primary reconstruction. By measuring successive bladder capacities within the first 5 years of life, we compared the rate of bladder growth in children with failed vs successful initial closure., Materials and Methods: We used an approved bladder exstrophy database to identify and review retrospectively patients with classic bladder exstrophy who underwent repeat cystograms between ages 1 and 6 years. Two groups of patients were identified--those with successful neonatal closure (group 1) and those with successful reclosure after an initial failed procedure (group 2). A generalized linear mixed model was fit to evaluate the impact of treatment group and age on bladder growth., Results: We identified 48 patients in group 1 (75% male) and 62 in group 2 (71% male). Initial pelvic osteotomy was done in 60% of group 1 and 34% of group 2. Patients in group 1 had significantly larger cystographic capacity at 2, 4, 5 and 6 years after successful bladder closure compared to those in group 2 (p <0.05). The bladder tended to grow at a significantly slower rate in group 2 (9.38 cc yearly) compared to group 1 (14.76 cc yearly, p = 0.005)., Conclusions: Patients with initial failed bladder exstrophy closure showed significantly smaller cystographic capacities and slower bladder growth compared to those who underwent successful neonatal bladder closure. These data clearly underscore the importance of a secure, successful primary closure., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The reasons for referral and treatment strategies in patients who underwent complete primary repair of bladder exstrophy elsewhere in the newborn period were evaluated., Materials and Methods: An institutionally approved database identified patients who underwent complete primary repair of exstrophy and were subsequently referred for continued care., Results: A total of 10 females and 55 males were referred for treatment between 1996 and 2010. Six females and 23 males were referred for complications following initial complete primary repair of exstrophy. Female complications included dehiscence (3 patients), prolapse (2) and stricture (1). Male complications included dehiscence (10 patients), prolapse (9), pubic separation (1) and stricture (3). Nine males had posterior urethral loss and 13 had major penile soft tissue injuries. Grade V vesicoureteral reflux and severe hydronephrosis were seen in the 4 patients with urethral strictures. Patients with dehiscence or prolapse underwent successful reclosure with osteotomy. Cases with posterior urethral loss or strictures were repaired with grafts. Four females and 32 males were referred for incontinence. Nine of these patients had poor bladder capacity, of whom 5 underwent bladder augmentation with continent stoma and 4 are awaiting further bladder growth. A total of 27 patients underwent bladder neck repair, with 15 (56%) subsequently continent, 5 (19%) daytime continent with nocturnal incontinence and 7 (26%) continuously incontinent. At initial closure osteotomy had been performed in all patients who were continent following bladder neck reconstruction and in 4 of 5 who were daytime continent., Conclusions: Complications of complete primary repair of bladder exstrophy can result in undesired upper urinary tract changes and penile soft tissue loss. Surgical reconstruction of such complications and acceptable continence are attainable in select cases., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The increasing incidence of hypospadias is partly attributed to increased gestational exposure to endocrine disruptors. We investigated the effects of genistein, the primary phytoestrogen in soy, on the molecular program of male urethral development., Materials and Methods: Female mice were fed diets supplemented with genistein (500 mg/kg diet) or control diets before breeding and throughout gestation. Urethras from embryonic day 17.5 male fetuses were harvested, and RNA was prepared, amplified, labeled and hybridized on whole genome microarrays. Data were analyzed using packages from the R/Bioconductor project. Immunohistochemical analysis and immunoblotting were used to confirm the activity of MAPK and the presence of Ntrk1 and Ntrk2 during urethral development., Results: Gestational exposure to genistein altered the urethral expression of 277 genes (p <0.008). Among the most affected were hormonally regulated genes, including IGFBP-1, Kap and Rhox5. Differentially expressed genes were grouped into functional pathways of cell proliferation, adhesion, apoptosis and tube morphogenesis (p <0.0001), and were enriched for members of the MAPK (p <0.00001) and TGF-β (p <0.01) signaling cascades. Differentially expressed genes preferentially contained ELK1, Myc/Max, FOXO, HOX and ER control elements. The MAPK pathway was active, and its upstream genistein affected tyrosine kinase receptors Ntrk1 and Ntrk2 were present in the developing male urethra., Conclusions: Gestational exposure to genistein contributes to hypospadias by altering pathways of tissue morphogenesis, cell proliferation and cell survival. In particular, genes in the MAPK and TGF-β signaling pathways and those controlled by FOXO, HOX and ER transcription factors are disrupted., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Few groups have examined health related quality of life for adolescents with bladder exstrophy-epispadias. We studied parent reported health related quality of life for adolescents with bladder exstrophy-epispadias using the Child Health Questionnaire-Parent Form 50., Materials and Methods: We recruited 11 to 17-year-old participants with bladder exstrophy-epispadias and their parents. Parents served as proxy respondents for the adolescents by self-administering a validated generic health related quality of life instrument, the Child Health Questionnaire-Parent Form 50. We collected urinary incontinence, catheterization status, and medical and surgical history data. Mean questionnaire scores were compared to population based norms., Results: Median age of the 55 patients was 14 years, 69% were male and 84% were white. Diagnoses included bladder exstrophy in 48 cases and epispadias in 7. Of the participants 29 (53%) reported urinary incontinence. The median number of lifetime surgeries was 9. Although physical and psychosocial summary measure scores were comparable to norms, the mean general health perception score was significantly worse than that of a population based sample (65.8 points, 95% CI 61.4-70.2 vs 73, 95% CI 71.3-74.7, p = 0.004). Mean family activity and parent emotional impact scores were also significantly worse than in a population based sample (83.6 points, 95% CI 79.3-88.0 vs 89.7, 95% CI 87.9-91.5, p = 0.02 and 67.7, 95% CI 61.9-73.6 vs 80.3, 95% CI 78.4-82.2, p <0.0001, respectively). Comparison of incontinent to continent children revealed a lower mean score on the parent emotional impact scale (62.6 points, 95% CI 55.5-69.8 vs 73.4, 95% CI 63.9-82.9), which approached significance (p = 0.06)., Conclusions: Although overall adolescent quality of life was comparable to norms, parents reported significantly impaired adolescent general health and family activity as well as a negative parental emotional impact. Further research is needed to identify interventions that can decrease the adverse impact of bladder exstrophy-epispadias on family activity and parent emotional distress., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The omphalocele-exstrophy-imperforate anus-spinal defects complex is a severe multisystem congenital defect. To comprehensively care for these patients one must appreciate the neurological and orthopedic impact on the overall health of the child., Materials and Methods: We retrospectively reviewed the medical records of 73 children with omphalocele-exstrophy-imperforate anus-spinal defects who were treated at our institution, identifying neurological and orthopedic anomalies, ambulatory ability and voiding status., Results: No neurological data were available on 5 patients. Of the remaining 68 patients 9 had no spinal anomaly, 57 had spina bifida, 1 had hemivertebrae and 1 had coccygeal hypoplasia. We further classified the 47 spina bifida cases as spina bifida occulta in 6, meningocele/lipomeningocele in 12, myelomeningocele/lipomyelomeningocele in 24 and sacral agenesis in 6. Of the patients with spina bifida 35 had cord tethering. Commonly identified orthopedic anomalies were vertebral malformation in 59 patients, scoliosis in 25, clubfoot in 14 and limb length discrepancy in 8. Ambulatory status in 62 patients of walking age revealed that 37 ambulated fully, 15 ambulated with devices, 2 ambulated minimally with devices and 8 were wheelchair bound. Continence data were available on 61 closed cases. Of these patients 26 were incontinent, including 3 with conduit diversion, 1 with ureterostomy and 1 with vesicostomy. A total of 35 patients were socially continent, of whom 30 catheterized via a continent abdominal stoma and 5 voided/catheterized via the urethra., Conclusions: Early evaluation for neurosurgical and orthopedic anomalies is vital in these children. Despite the high incidence of spinal pathology most patients ambulate without assistance. Few children with omphalocele-exstrophy-imperforate anus-spinal defects achieve continence via the urethra. Vigilant followup is necessary to identify potentially correctable conditions., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We describe the application and results of modified Young-Dees-Leadbetter bladder neck reconstruction after successful complete primary repair in the newborn period., Materials and Methods: The records of 34 patients referred for a continence procedure after successful exstrophy closure were extracted from an institutionally approved database. Patient characteristics and surgical outcomes were assessed., Results: A total of 31 male and 3 female patients were identified, of whom 27 and 1, respectively, underwent osteotomy at initial closure. No patients attained urinary continence and so they were referred for a continence procedure. Nine patients did not have adequate bladder capacity for bladder neck repair (mean bladder capacity 63 ml, range 20 to 80). In those with suitable capacity mean capacity was 119 ml (range 85 to 180) and they underwent bladder neck reconstruction at a mean age of 4.9 years. Of the 25 patients who underwent bladder neck repair 14 (56%) were dry during the day and night, 5 (20%) were dry during the day but wet at night and 6 (24%) were totally incontinent. Pelvic osteotomies were performed at initial closure in 14 totally continent patients (100%) and in 4 (80%) with daytime continence but in no totally incontinent patients. All continent patients underwent hypospadias repair before age 1 year and none required ureteral reimplantation before bladder neck repair., Conclusions: A number of patients require bladder neck reconstruction to achieve continence after successful initial closure with complete primary repair. The modified Young-Dees-Leadbetter technique provides reasonable results with daytime and nighttime dryness attained by more than half of the patients.

Purpose: We report the indications, technique and outcome of a large series of children who underwent bladder neck transection for intractable urinary incontinence., Materials and Methods: We retrospectively reviewed demographics, operative details, complications and outcomes of 76 patients (47 males, 29 females) who underwent bladder neck closure at our institution between 1996 and 2006. Mean patient age at the time of the procedure was 12 years, 10 months. The most common diagnosis was bladder exstrophy. Of the patients 31 had undergone prior bladder neck reconstruction (30) or sling repair (1). All patients underwent concomitant augmentation and creation of a catheterizable stoma., Results: A total of 50 patients had more than 12 months of followup (mean 44, range 12 to 128). Continence was achieved initially in 86% of the patients (43 of 50). Of the 7 primary failures 2 leaked via the urethra and 5 via the stoma. Six of these patients achieved dryness with revision, for a final continence rate of 98%. A single renal unit suffered significant loss of function during this period. New, nonobstructive hydronephrosis developed in 8 additional renal units. Stones developed in 30% of the patients. There were no spontaneous bladder ruptures., Conclusions: Bladder neck transection in combination with enterocystoplasty and creation of a continent catheterizable stoma is an effective approach to incontinent cases with severely damaged bladder outlets and poor quality bladders in which other reconstructive approaches either have failed or are deemed likely to fail. Specific concerns regarding the risk of poor renal outcomes and perforation seem unwarranted at present.

Purpose: The complications of lower urinary tract reconstruction have been well documented in children with neurogenic bladders. While most series include small numbers of nonneurogenic diagnoses, this group is typically underrepresented. Despite a number of fundamental anatomical and functional differences, a direct comparison of surgical complications of lower urinary tract reconstruction in patients with neurogenic vs nonneurogenic bladders has not been performed., Materials and Methods: We identified patients undergoing lower urinary tract reconstruction incorporating enterocystoplasty from 1996 to 2006. We performed a retrospective review of operative notes and medical records of patients who met inclusion criteria. Patients were divided into a neurogenic group and a nonneurogenic group based on the underlying diagnosis. The 2 groups were compared with respect to demographics, historical data, operative techniques, perioperative morbidity, long-term complications and need for surgical revision., Results: Of the 127 patients who met inclusion criteria 72 were assigned to the nonneurogenic group and 55 to the neurogenic group. Overall the rates of significant perioperative morbidity (39%), long-term complications (54%) and need for surgical revision (39%) were substantial. The rates of catheter related complications, rehospitalization for dehydration and spontaneous bladder rupture were higher in the neurogenic group (p <0.05)., Conclusions: Reconstruction of the lower urinary tract in children is associated with a considerable rate of complications and need for surgical revision regardless of whether the bladder is neurogenic or nonneurogenic. Children with neurogenic bladders are more prone to spontaneous rupture, catheter mishaps and early rehospitalization for dehydration.

Purpose: We studied the impact of abnormal bladder function due to congenital urological disorders on health related quality of life in children. A reliable patient based method is needed to assess the impact of these conditions in children and the interventions used to treat them., Materials and Methods: Participants 11 to 17 years old with bladder exstrophy-epispadias complex, spina bifida or other causes of abnormal bladder function self-administered the Child Health and Illness Profile-Adolescent Edition, a generic health related quality of life instrument. They also responded to questions about incontinence, catheterization status and bother level. Mean scores on the profile were compared to population based norms., Results: Mean age of the 50 participants was 14.9 years, 62% were male and 82% were white. Diagnoses included bladder exstrophy-epispadias complex in 37 patients, spina bifida in 10 and other in 3. The mean +/- SD score on the disorders domain of 14.2 +/- 6.3 was significantly worse than the population norm of 20. Mean scores on the satisfaction, discomfort, resilience, risks and achievement domains were comparable to or better than the population based norm of 20. A total of 29 participants reported incontinence and 31 performed catheterization., Conclusions: In this study of adolescents with congenital causes of abnormal bladder function Child Health and Illness Profile-Adolescent Edition generic health related quality of life scores were significantly worse in the disorders domain but largely comparable to or better than those of the general population in other domains. This suggests that the profile may discern between adolescents with structural urological disease and norms but it may not be sensitive enough to fully detect the impact of the condition. Alternatively adolescents may adapt well to the challenges of urological disease.

Purpose: This is a retrospective series of the surgical management of complete androgen insensitivity at a single institution., Materials and Methods: The records of 16 patients 4 to 63 years old with complete androgen insensitivity were extracted from an institutionally approved database. We determined whether each patient underwent vaginoplasty, age at vaginoplasty, vaginal depth before vaginoplasty, age at gonadectomy and whether the patient was sexually active. These data were pooled with those from a prior study at our institution to yield a total of 29 patients., Results: All patients had undergone gonadectomy with no evidence of malignancy in any pathology specimens. Of the 27 patients in whom the date of surgery was known 20 underwent surgery in late adolescence/adulthood, while 7 had the testes removed in childhood. Of the 29 patients 11 (38%) have undergone vaginal reconstruction. Average vaginal depth in postpubertal patients without reconstruction was 6.6 cm (range 1.5 to 10). Preoperative vaginal depth in patients with was between 2 and 4 cm. Ten postpubertal patients have undergone vaginoplasty and 7 (70%) are sexually active. Of the postpubertal patients 15 have not undergone vaginoplasty, of whom 12 (80%) are sexually active., Conclusions: A delayed approach to gonadectomy and vaginal reconstruction respects patient autonomy and allows a more mature patient to handle the psychological and physical trauma of surgery and rehabilitation. Since we recognize the small number of patients in this series, strict guidelines cannot be proposed.

Purpose: We report the urological, orthopedic and neurological complications of primary closure of classic bladder exstrophy using modern staged repair of exstrophy., Materials and Methods: An approved database identified 137 males and 57 females with classic bladder exstrophy who underwent primary repair by 1 of 2 surgeons in 23 years. A total of 185 patients underwent primary closure using modern staged repair of exstrophy with or without osteotomies, whereas 9 underwent delayed primary closure with epispadias repair at age 12 months. Of the patients 63 received osteotomies. Mean age at closure was 60 days and mean followup was 9 years., Results: There were 14 major complications (11%) and 27 minor complications (14%). Major urological complications included bladder prolapse or dehiscence in 6 male patients (3%), which was successfully reclosed. Major orthopedic complications, including osteotomy nonunion in 2 cases, leg length inequality in 1 and persistent joint pain in 1, developed in 4 of the 63 patients (6%) who underwent osteotomy. Major neurological complications included femoral nerve palsy in 4 patients (2%). There were 21 minor urological complications (11%), including posterior bladder outlet obstruction in 4 cases, urethrocutaneous fistula in 2, suprapubic tube removal in 2, intrapubic stitch erosion in 4, febrile urinary tract infection in 6 and surgical site infection in 3. Six patients (3%) had minor orthopedic complications, including pelvic osteomyelitis in 1, pin site infection in 3 and a pressure sore from immobilization in 1., Conclusions: Closure of bladder exstrophy is a safe surgery with an acceptable risk of complications. A critical review of outcomes provides insight to further refine the technique and manage complications when they develop.

Purpose: We evaluated the current application of Duckett paraexstrophy skin flaps for bladder exstrophy reconstruction., Materials and Methods: We reviewed the records of cases of classic exstrophy treated at our institution between September 1993 and March 2007. A total of 21 patients were identified in whom modified Duckett paraexstrophy skin flaps were used in bladder closure at our institution. Another 12 patients were referred during the same time after closure with complications with flap use., Results: Of the 21 patients who underwent closure at our institution with our modified version of the Duckett flaps 1 (4%) had a complication, that is urethral stricture. This responded to internal urethrotomy and daily intermittent catheterization for 4 months, and the stricture stabilized. Four of the 12 referred patients responded to multiple urethral dilations, 3 underwent open repair with a buccal graft, 2 received a full-thickness skin graft and 3 underwent internal urethrotomy with daily intermittent catheterization for 4 months. Of our 21 patients with internal treatment 14 underwent bladder neck repair, 5 underwent epispadias repair and 2 were awaiting further reconstruction. Six of the 12 referred patients underwent bladder neck repair, 4 underwent epispadias repair and 2 were awaiting further reconstruction., Conclusions: By modifying our version of the Duckett paraexstrophy skin flaps we have lowered our complication rate significantly. While overall use of these flaps has continued to decrease, when they are required, these modifications help avoid complicating strictures and their sequelae in the bladder and upper urinary tract.

Purpose: We used current methods of screening for prostate cancer, digital rectal examination and serum prostate specific antigen as an initial assessment of risk in a young group of adult 46,XY patients affected by disorders of sex development., Materials and Methods: Adult intersex patients older than 21 years, under long-term followup at the Pediatric Endocrinology Clinic of the Johns Hopkins Hospital, with a diagnosis of male psuedohermaphroditism and raised as male or female were included in analysis. After written consent all participants underwent digital rectal examination and blood sampling for prostate specific antigen and testosterone measurements., Results: Prostate specific antigen values were available for analysis in 26 patients. Diagnoses included micropenis (8), complete androgen insensitivity syndrome (3), partial androgen insensitivity syndrome (9) and mixed gonadal dysgenesis (6). Of the 26 patients 9 had been raised as female (complete androgen insensitivity syndrome in 3, partial androgen insensitivity syndrome in 3, micropenis in 2 and mixed gonadal dysgenesis in 1). Mean patient age was 38 years (range 24 to 57). Serum prostate specific antigen was less than 0.1 ng/ml in 18 patients including the 9 reared as female. The remaining 8 patients had a prostate specific antigen of 0.1 to 0.9 ng/ml, were reared as male and had a mean age of 39.6 years (range 33 to 44). The diagnoses in this group consisted of micropenis (4), partial androgen insensitivity syndrome (2) and mixed gonadal dysgenesis (2). All patients had a palpable, small prostate gland with no abnormalities noted on digital rectal examination., Conclusions: This study found measurable prostate specific antigen in a subset of male intersex patients that were comparable to controls matched for age and race. We recommend that patients with 46,XY disorder of sex development, reared as male, be screened for prostate cancer in a manner similar to men not affected by disorder of sex development.

Purpose: Currently chronic illness is not a recognized risk factor for suicide in children. Therefore, we evaluated vulnerability for suicidal behavior (suicide attempt and suicidal ideation) in our population of young patients with classic bladder exstrophy., Materials and Methods: We reviewed the charts of 121 patients 5 to 24 years old with classic bladder exstrophy only from a combined, 2-center database of 935. These patients were psychologically evaluated from 1996 to 2005 for preoperative readiness for urological surgery or for coping with medicosurgical health requirements., Results: Of 121 patients 18 (14.9%) experienced suicidal ideation. Of 38 patients (31.4%) older than 14 years 11 experienced suicidal ideation, 2 experienced a serious suicidal attempt and 1 completed suicide. In 36 patients (30%) there were no recorded data on suicidal behavior. All patients with suicidal behavior were male., Conclusions: Data from this study of classic exstrophy imply that there are clinically significant vulnerabilities for suicidal behavior in affected male children, adolescents and young adults. These findings argue for screening those with classic exstrophy for suicidal behavior and psychopathology.

Purpose: Patients with bladder exstrophy and failed primary newborn closure or who undergo delayed primary repair have suboptimal functional outcomes. We sought to determine whether these patients also have costlier, more resource intensive hospitalizations compared to patients who undergo neonatal primary closure., Materials and Methods: We reviewed hospital coding records to identify patients who underwent surgical repair of classic bladder exstrophy at The Johns Hopkins Hospital between 1997 and 2006, and obtained charge records for each hospitalization. Total hospital charges (excluding professional fees) were inflation adjusted to year 2005 dollars. Cases were identified as newborn primary repair, delayed primary repair or reclosure of failed prior repair., Results: Results of classic exstrophy repair were analyzed in 80 patients. A total of 34 procedures were newborn primary repairs, 15 were delayed primary repairs and 31 were reclosures of failed prior repair. All of the patients undergoing delayed primary repairs and reclosures underwent osteotomy, compared to only 21% of those undergoing newborn primary repair. Overall mean inflation adjusted hospitalization charge was $66,348 +/- $26,625 (range $29,689 to $179,403). Newborn closures were significantly less costly (mean charge $53,188 +/- $15,086) than either reclosure ($71,621 +/- $19,366) or delayed primary closure ($85,278 +/- $42,354, p <0.0001). Controlling for multiple variables in a regression model showed that the primary factors associated with charges were operative time, days in intensive care unit and length of stay. Length of stay and operative times were significantly shorter in the newborn surgical group, likely accounting for the lower costs in this group (despite higher intensive care unit use). Mean hospital charges and mean length of stay increased during the study period., Conclusions: Primary newborn exstrophy repair is associated with lower surgical hospitalization costs compared to delayed primary repair and reclosure. Combined with previous data on clinical outcomes, these data reiterate the paramount importance of achieving a successful initial newborn closure whenever possible.

Purpose: We describe the results of modified Young-Dees-Leadbetter bladder neck reconstruction to achieve continence in patients who underwent complete primary repair of bladder exstrophy as newborns., Materials and Methods: Using the Johns Hopkins Exstrophy Database we identified patients who underwent bladder neck reconstruction after having undergone complete primary repair of bladder exstrophy as newborns. We determined patient characteristics and surgical outcomes., Results: A total of 30 males and 3 females were referred after complete primary repair of bladder exstrophy, of whom 26 underwent bladder neck reconstruction. Results of complete primary repair of bladder exstrophy were strongly associated with osteotomy use. Of the patients 19 (58%), including 16 males and 3 females, who underwent complete primary repair of bladder exstrophy without osteotomy had complications (dehiscence and bladder prolapse), while none of 14 male patients who underwent complete primary repair of bladder exstrophy with osteotomy had complications, although none were subsequently continent. Of the 19 patients who had complications after complete primary repair of bladder exstrophy 12 underwent bladder neck reconstruction and total continence was achieved in only 3 (25%). Of the 14 patients with successful complete primary repair of bladder exstrophy 8 (57%) are dry day and night, 4 (28%) are dry during the day and wet at night, and 2 (14%) are completely incontinent. Continent children underwent successful complete primary repair of bladder exstrophy with pelvic osteotomy, all underwent hypospadias repair before age 1 year and none required ureteral reimplantation before bladder neck reconstruction., Conclusions: Many patients who undergo newborn complete primary repair of bladder exstrophy will require bladder neck reconstruction. Bladder neck reconstruction is more successful in those in whom complete primary repair of bladder exstrophy was successful. As in all types of repair, failed initial closure usually results in a bladder that is unsuitable for bladder neck reconstruction. These patients often require bladder augmentation and a continent stoma to be dry.

Purpose: Staged pelvic closure has been shown to be beneficial in achieving pubic approximation in children with the exstrophy-epispadias complex. We have continued to use this procedure in children with extreme pelvic diastasis and have updated our experience., Materials and Methods: We performed closure of the pelvis in 15 patients 12 months to 14 years old presenting with a pubic diastasis of at least 8 cm (range 8 to 16). Of the patients 14 had cloacal exstrophy and 1 had classic exstrophy. Two patients with cloacal exstrophy and the patient with classic exstrophy had prior complete dehiscence at primary closure, and 1 patient with cloacal exstrophy had partial dehiscence. The technique involved bilateral innominate and vertical iliac osteotomy, and placement of a bony fixator with interfragmentary pins. The fixator was gradually closed, and soft tissue and pelvic ring closure occurred 2 to 3 weeks later. In 9 of the 15 patients an interpubic stainless steel plate was used to keep the pubis in apposition at the time of bladder closure., Results: At a mean followup of 5.5 years (range 6 months to 14 years) closure was successful in all 15 patients. One patient (age 12 months) had loosening of the pin between stages, which was salvaged with pin replacement. One patient had ureteral obstruction from hematoma after pin placement without direct pressure from the pins or bone. None of the patients had dehiscence or prolapse., Conclusions: This technique of staged pelvic closure can be used in the setting of primary or secondary pelvic reconstruction in patients presenting with extreme pelvic diastasis. The gradual reduction in diastasis allows gradual stretching of the soft tissues. It converts a major reconstruction challenge into 2 well tolerated components. However, the procedure is not recommended in children younger than 1 year due to the possibility of the pins loosening during diastasis reduction.

Purpose: We describe the complications of complete repair and their management., Materials and Methods: A total of 19 patients were referred after failed complete repair. Total dehiscence occurred in 6 males, major bladder prolapse in 3, minor prolapse in 3, pubic separation in 1, impassable stricture in 1, and total hemiglans and corporal loss in 2. Overall, partial glans loss was seen in 7 patients, urethral loss in 5 and penile skin loss in 3. One female had complete dehiscence and 1 had major prolapse, both losing the urethrovaginal septum. One female had an impassable stricture., Results: Six males with dehiscence underwent re-closure with osteotomy. Urethral replacement was performed with full thickness skin graft (FTSG) in 3 and with buccal mucosa in 3. Five patients underwent a modified Cantwell-Ransley (C-R) epispadias repair after placement of skin expanders, and 1 awaits repair. The 3 patients with major prolapse underwent re-closure with osteotomy. A urethral buccal graft was used in 1 patient, FTSG was used in 2 at a later operation and all 3 underwent C-R epispadias repair. Of the 3 patients with minor prolapse 2 underwent re-closure with osteotomy using urethral buccal graft or FTSG followed later with a C-R repair. The final patient with minor prolapse underwent re-closure with osteotomy and C-R repair after testosterone stimulation. One patient with pubic separation and urethral and skin loss underwent re-closure with osteotomy, C-R repair after skin expanders and later bladder neck repair. In 1 case a ureteral graft replaced a posterior urethral stricture. Of the 2 patients with hemiglans and corporal loss 1 underwent penile torsion repair and later hypospadias repair, while the other is being observed. Two females underwent re-closure with osteotomy and urethral replacement with tubularized bladder. The case of stricture was managed endoscopically., Conclusions: Complications of complete repair are similar to those of other repairs but more serious if soft tissue loss occurs. Because of these increased risks, this procedure and its formidable complications are best managed by experienced exstrophy surgeons.

Purpose: Bladder exstrophy is a rare condition, and data are lacking regarding practice patterns in its surgical management. We used a large nationwide database to investigate practice patterns of bladder exstrophy repair., Materials and Methods: We used the Nationwide Inpatient Sample (1988 to 2000) to identify patients who underwent surgical repair of bladder exstrophy (International Classification of Disease-9 code 578.6). We analyzed factors affecting practice patterns and outcomes. Hospital volume was based on caseload during the highest volume year of study participation (high volume 5 or more, mid volume 3 to 4 and low volume less than 3 cases)., Results: We identified 407 cases. Approximately half of the patients (53.2%) were hospitalized within 24 hours of birth, although 28% of patients were older than 1 year. Of the patients 54% were male. Exstrophy repair is extremely resource intensive. In this series mean length of hospital stay (LOS) was 24.6 +/- 22.8 days, and mean inflation adjusted hospital charges were 62,302 dollars (median 39,978 dollars). High volume hospitals (HVHs) had lower hospital charges (37,370 dollars) than mid volume (51,778 dollars) or low volume hospitals (LVHs, 50,474 dollars, p = 0.0095). On multivariate regression HVHs had lower charges even after controlling for other significant predictors, including LOS (p <0.0001). Patients at HVHs were more likely to undergo osteotomy (p = 0.007). Six patients died after exstrophy repair (1.5%), all of whom had been born prematurely (p <0.0001). Although death was more likely at LVHs, this was due to the fact that more patients at LVHs were born prematurely (4.2% at HVHs vs 5.9% at mid volume hospitals and 11.1% at LVHs, p = 0.027)., Conclusions: Bladder exstrophy repair carries a high risk of morbidity and is resource intensive. Variations between high and low volume hospitals in practice patterns and case mix may contribute to observed differences in resource use, LOS and clinical outcomes.

Purpose: Variants of the bladder/cloacal exstrophy complex are rare. Different presentations and subsequent management and outcome are discussed., Materials and Methods: We performed a retrospective review of our database of more than 815 patients with the exstrophy complex. Patients with variants of classic epispadias or bladder or cloacal exstrophy were identified. Anatomical presentation, surgical management, type of continence procedures and final outcome were evaluated., Results: Of the 25 patients with variants 13 were treated primarily at our institution and 12 were referred. Time until primary bladder closure ranged from 1 day to 4 years. Followup after continence procedure ranged from 1 month to 39 years. Seven of the 25 patients are awaiting a continence procedure. Six patients are dry without a continence procedure, of whom 4 have superior vesical fistulas. A total of 11 patients underwent bladder neck reconstruction (BNR), of whom 3 are dry, 2 are dry during the day but are wet at night, 1 had a failed procedure and 5 are dry after continent diversion (CD). One additional patient underwent CD initially and is dry. Referred cases of epispadias with bladder prolapse were not recognized at birth and had delayed closure. Impaired bladder growth or failed BNR required CD in 4 patients, and 2 are awaiting a continence procedure. Skin covered and duplicate exstrophy had comparable outcomes to the classic presentations. Duplicated organs were used for reconstructive procedures. Of the 6 patients with cloacal variant 2 are continent of stool and 2 await a Pena procedure. One of these patients has an ileal stoma and 1 has a colostomy., Conclusions: The initial presentation of exstrophy variants can be confusing, often delaying initial treatment. Superior vesical fistulas permit continence without BNR due to an intact urinary sphincter. Variants such as epispadias with bladder prolapse and duplicate or skin covered exstrophy should be closed at birth with standardized techniques to promote bladder growth for later BNR. These cases are faced with the same long-term problems as the classic presentation. Cloacal variants can present with intact anal innervation, allowing a later Pena procedure.

Purpose: We provide a 3-dimensional (3D) model of the pelvic floor musculature in patients with classic bladder exstrophy using magnetic resonance imaging (MRI)., Materials and Methods: Five male infants 1 day to 12 months old underwent MRI of the pelvis, which was compared to pelvic MRI of 1 male infant without pelvic floor abnormalities. Of the patients 3 were studied before primary closure and 2 before reclosure. None of the patients had a prior pelvic osteotomy. While the entire pelvic floor was imaged, special attention was paid to the contours of the levator ani muscle group which were drawn on T1-weighted axial and coronal images. The overlap of contours in these 2 planes was used to construct a 3D model of this muscle group. The diastasis of the pubic symphysis was also measured for all patients on a plain pelvic radiograph., Results: The levator ani muscle group conformed to an elliptical dome shape in the control. For the patients the 3D shape was somewhat irregular with an apparent kink in the ellipse. The elliptical shape of the group was described by a shape factor, s, which equals the ratio of the maximum height-to-the length of the base of the ellipse. The shape factor was equal to 0.176 in the control compared to a mean of 0.448 for the patients. There was no relationship between diastasis of the pubic symphysis and the extent of disproportionate curvature of the levator group., Conclusions: To our knowledge this is the first qualitative description of the pelvic floor anatomy in bladder exstrophy using MRI. Our model gives further insights into the true pelvic floor anatomy in exstrophy cases and is the first to suggest that abnormalities in the pelvic floor may not correlate with abnormalities of the bony pelvis.

Purpose: Stone formation following bladder or continent reservoir reconstruction in children is a major source of long-term morbidity. We determine whether the method of stone removal (fragmentation or intact extraction) affected the time to stone recurrence in children after bladder reconstruction., Materials and Methods: Medical records from 1993 to 2003 were examined to identify patients with urinary reconstruction subsequently treated for bladder calculi at our institution. Retrospective review of the medical records was performed to determine the type of urinary reconstruction, time to stone recurrence, method of stone removal and length of followup. Kaplan-Meier analysis was performed with each stone episode considered as an individual event. Time to recurrence was measured in months from stone removal to identification of recurrent stones., Results: A total of 60 patients with bladder or continent reservoir reconstructions had undergone 103 stone removal procedures (range 1 to 8 procedures per patient). Patients were rendered stone-free after each procedure. Stones recurred following 42.4% of intact and 43.9% of fragmented extractions at a mean of 27.0 (SD 31.3) and 27.6 (SD 21.8) months, respectively. Kaplan-Meier survival analysis curves for intact and fragmented extractions were not statistically different., Conclusions: Time to stone recurrence in patients with bladder or continent reservoir reconstruction is not altered by the method of stone removal (fragmented versus intact extraction). Since recurrence remains a frequent problem in children after bladder augmentation and/or reconstruction, use of the least invasive modality should be the initial management recommendation.

Purpose: Successful initial surgical management of bladder exstrophy does not always lead to continence. We evaluated the ultrastructure of the exstrophic bladder using electron microscopy (EM) at various stages of reconstruction to determine whether morphology could correlate with the potential for continence., Materials and Methods: Bladder specimens obtained from 32 patients undergoing various stages of exstrophy reconstruction were evaluated by EM. Specimens were obtained at primary newborn closure (group 1-10), reclosure following failure (group 2-2), bladder neck reconstruction (group 3-9) and augmentation cystoplasty (group 4-11). Evaluation was performed by a single anatomist with experience with EM. Biopsies were separated into those with good, intermediate or poor ultrastructural parameters and then correlated clinically., Results: In group 1, 4 children had good and 2 had intermediate parameters. All showed increased bladder volumes at followup. Four patients had poor parameters and poor bladder growth. The 2 group 2 children had poor parameters and bladder growth. In group 3, 7 of 9 patients had good and 1 had intermediate parameters. Eight of the 9 patients are doing well. Only 3 of the 11 group 4 children had good parameters and an additional 2 had intermediate parameters., Conclusions: Ultrastructural evaluation can identify changes in the bladder that may portend a poor prognosis for eventual continence. Although the correlation was good at bladder closure, some patients with good parameters still had failed reconstruction. Since this is a small study, we continue to recommend reconstruction in all patients who have an adequate bladder template.