Rare exonic CELSR3 variants identified in Bladder Exstrophy Epispadias Complex.

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

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.

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

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

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

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

Urothelial Differences in the Exstrophy-Epispadias Complex: Potential Implications for Management.

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.

Continence after BNR in the complete repair of bladder exstrophy (CPRE): A single institution expanded experience.

INTRODUCTION: Several surgical methods have been used for primary repair of bladder exstrophy in the newborn. Complete primary repair of exstrophy (CPRE) aims to prevent the need for surgeries beyond the newborn period. Due to the rarity of bladder exstrophy, it has proven difficult in the past to analyze whether use of this method of closure truly does confer acceptable continence outcomes and hence minimizes the requirement for additional surgeries later in life. OBJECTIVE: To describe the continence outcomes of CPRE patients who went on to receive bladder neck reconstruction (BNR), and secondarily, to compare clinical features between those patients who were able to receive undergo a BNR compared to those who were not. STUDY DESIGN: An IRB approved database of 1330 exstrophy-epispadias patients was used to identify referred patients after successful CPRE for management of continued urinary incontinence. Urinary continence outcomes were assessed in those who underwent modified Young Dees Leadbetter BNR following CPRE. RESULTS: Sixty-one patients were referred for treatment after successful CPRE between 1996 and 2016. None developed continence or a dry interval after primary closure. Of these, forty-two (68.9%) underwent BNR by a single surgeon at a mean age of 5.8 years (range 5-8.4). The mean bladder capacity at BNR was 147 mL (range 102-210 mL). Twenty-five (59.5%) achieved day and night continence, 7 (16.7%) gained daytime continence with nocturnal leakage, and 10 (23.8%) remain totally incontinent. Mean follow-up after BNR was 5.9 years. Combined CPRE and pelvic osteotomy were performed in 100% of patients who were continent and 75% of those who were daytime dry. No continent patient had a ureteral reimplantation before BNR, whereas 4 patients with daytime continence and nocturnal leakage and 7 patients who remained continuously incontinent did. DISCUSSION: This is the largest known series of BNRs in exstrophy patients closed by CPRE. Previous smaller studies have demonstrated mild to moderate success rates of BNR after CPRE, with many patients still requiring additional continence surgeries. The present study found similar results, with additional indication that successful primary closure and use of pelvic osteotomies may correlate with enhanced continence. This study includes outcomes from a single surgeon, with a maximum length of follow up of 13 years. CONCLUSIONS: CPRE alone often does not render patients continent of urine, based on the authors' referral population. However, following BNR continence rates in this subgroup were found to reach 76%. Surgeons who treat this population should keep these factors in mind when planning continence surgeries.

Penile Disassembly in Complete Primary Repair of Bladder Exstrophy: Time for Re-evaluation?

OBJECTIVE: To explore a series of classic bladder exstrophy (CBE) cases referred to the authors' institution where primary closure with penile disassembly epispadias repair was complicated by penile injury. The penile disassembly technique is frequently combined with bladder closure in patients with CBE undergoing the complete primary repair of exstrophy (CPRE). Penile disassembly has been posited as a risk for penile injury by ischemic mechanisms. METHODS: A prospectively-maintained institutional database of 1337 exstrophy-epispadias complex patients was reviewed for CPRE cases referred to the authors' institution, and those with injury to the penis were identified. The location, extent of injury, and subsequent management is reported. RESULTS: One hundred and thirteen male CBE patients were referred after prior CPRE. Twenty-six (20%) were identified with penile loss and reviewed. Eighty-one percent were closed in the neonatal period, and 54% had a pelvic osteotomy. Median follow-up time was 9.9 years (range 0.6-21.3). Of 26 patients with penile loss, 77% had unilateral loss and in 23% had bilateral loss involving the glans and/or one or both corpora cavernosa. Three patients were successfully managed with myocutaneous neophalloplasty. CONCLUSION: Complete penile disassembly during bladder exstrophy closure may lead to penile injury. This major complication questions the continued application of complete penile disassembly in the reconstruction of bladder exstrophy.

Urinary Continence Outcomes in Classic Bladder Exstrophy: A Long-Term Perspective.

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.

The dual-staged pathway for closure in cloacal exstrophy: Successful evolution in collaborative surgical practice.

INTRODUCTION: A successful abdominal wall and bladder closure is critical in the management of cloacal exstrophy (CE). This study examines closure outcomes and practices over the last 4 decades at the authors' institution. Beginning in 1995, the authors' institution standardized CE closure and management with the Dual-Staged Pathway (DSP). The DSP consists of a staged bladder closure, a staged or concurrent osteotomy, and postoperative immobilization with external fixation. The authors hypothesize that the DSP has provided better outcomes in CE closures. METHODS: A prospective database of 1332 Exstrophy-Epispadias Complex (EEC) patients was reviewed for CE patients closed between 1975 and 2015. The DSP consists of a staged osteotomy and a staged bladder closure in CE patients with a diastasis greater than 4 cm. To evaluate the DSP, outcomes of closure at the authors' institution were compared between two equal, twenty-year periods before and after its implementation. Data on timing of closure, postoperative management, surgical complications, and outcomes were collected. RESULTS: There are 142 CE patients in the database. In this study, 49 CE patients with 50 closures met inclusion criteria. The overall success rate of closures from 1975 to 1994 was 88% (14 of 16), while the success rate of the DSP was 100% (n = 34), p = 0.098. Twenty-two (65%) primary and 12 (35%) secondary closures were performed using the DSP. Overall complication rates of the DSP remained similar to previous closures, (29% vs 19%, p = 0.508). Since incorporation of the DSP, patients referred for closure have generally had a larger preclosure diastasis (7.2 cm vs 5.1 cm, p = 0.011). CONCLUSION: The standardized DSP closure has proven successful in 34 primary and reoperative cloacal closures in the past 20 years. With this approach, the authors feel that the DSP offers greater patient safety and better outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Diagnosis of hemophilia in newborn circumcision: A case presentation.

Circumcision is often the earliest surgery performed in a young male's life. Though complications in this procedure are rare, prolong postoperative bleeding may be the first sign of undiagnosed hemophilia. Hemophilia is a rare X-linked bleeding disorder and if not treated prophylactically or promptly during surgical intervention can be fatal. In this case presentation we describe the diagnosis of hemophilia in a child presenting with postoperative bleeding from circumcision. We review the literature regarding the history of this disease with early surgery and highlight the current treatments.

Variant Presentations of the Exstrophy-Epispadias Complex: A 40-Year Experience.

OBJECTIVE: To investigate the diagnosis, surgical management, and outcomes in patients with variant EEC. Variant presentations of the exstrophy-epispadias complex (EEC) span a wide range of abnormalities. The rarity and diversity of EEC variants can lead to challenges in the diagnosis and subsequent management of this population. METHODS: The authors reviewed an institutional database of 1336 EEC patients from 1975 to 2018 for variant presentations of EEC. Variant presentations included those with skin covered bladder exstrophy (BE), duplicate bladders, superior vesical fistula, and epispadias with major bladder prolapse. Surgical management and outcomes were assessed. RESULTS: In total, 44 EEC variants were identified. Nineteen (43%) presented with a skin-covered BE variant. Five patients presented with duplicate BE, while 6 presented with superior vesical fistula. Fourteen patients (32%) presented with epispadias with major bladder prolapse. Overall, 36 (82%) EEC variants underwent primary bladder closure, at a median of 135 days after birth (range 1-2010), with 21 (58%) undergoing pelvic osteotomy. Primary closures were successful in 89% of cases. Continence procedures were performed in 17 patients. This includes 5 patients who underwent bladder augmentation. However even without a continence procedure, continence with volitional voiding was found in 8 patients. CONCLUSION: The most common EEC variant is the skin-covered form of BE. In order to expedite appropriate management, accurate diagnosis upon initial presentation is crucial. Still, successful surgical reconstruction often results in continence that is similar to, or better than, nonvariant EEC presentations.

Novel Anatomical Observations of the Prostate, Prostatic Vasculature and Penile Vasculature in Classic Bladder Exstrophy Using Magnetic Resonance Imaging.

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.

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

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

Cytotoxic Necrotizing Factor-1 (CNF1) does not promote E. coli infection in a murine model of ascending pyelonephritis.

BACKGROUND: Urinary tract infections (UTI) are among the most common and costly infections in both hospitalized and ambulatory patients. Uropathogenic E. coli (UPEC) represent the majority of UTI isolates and are a diverse group of bacteria that utilize a variety of virulence factors to establish infection of the genitourinary tract. The virulence factor cytotoxic necrotizing factor-1 (CNF1) is frequently expressed in clinical UPEC isolates. To date, there have been conflicting reports on the role of CNF1 in the pathogenesis of E. coli urinary tract infections. RESULTS: We examined the importance of CNF1 in a murine ascending kidney infection/ pyelonephritis model by performing comparative studies between a clinical UPEC isolate strain and a CNF1-deletion mutant. We found no alterations in bacterial burden with the loss of CNF1, whereas loss of the virulence factor fimH decreased bacterial burdens. In addition, we found no evidence that CNF1 contributed to the recruitment of inflammatory infiltrates in the kidney or bladder in vivo. CONCLUSIONS: While further examination of CNF-1 may reveal a role in UTI pathogenesis, our data casts doubt on the role of CNF-1 in the pathogenesis of UPEC UTI. As with other infections, different models and approaches are needed to elucidate the contribution of CNF1 to E. coli UTI.

Repair of Vesicocutaneous and Urethrocutaneous Fistulae with Rectus Muscle Flap in a Bladder Exstrophy Patient.

Urinary continence can be achieved in up to 90% of patients with bladder exstrophy. However, select patients remain incontinent despite modern reconstruction. Repeat operations for continence combined with the congenital pelvic abnormalities of exstrophy put patients at risk for urinary fistula formation. We report the use of a rectus muscle flap in the repair of two concomitant vesicocutaneous and urethrocutaneous fistulae in a patient with classic bladder exstrophy.

Upper Pole Heminephrectomy Versus Lower Pole Ureteroureterostomy for Ectopic Upper Pole Ureters.

PURPOSE OF REVIEW: Ureteral duplication and ectopic upper pole ureters are commonly associated with renal pathology, including vesicoureteral reflux, obstruction, infection, and renal function loss. There remains no consensus on the most appropriate management of these complex patients. In this review, we sought to compare existing data on upper pole heminephrectomy with ipsilateral ureteroureterostomy. RECENT FINDINGS: Application of magnetic resonance imaging and minimally invasive techniques have led to changes in the diagnosis and treatment of ectopic upper pole ureters. Recent studies have highlighted the safety of laparoscopic and robot-assisted upper pole heminephrectomy and ureteroureterostomy. Minimally invasive approaches to ectopic upper pole ureters appear safe and effective, with complication rates remaining low. Minimally invasive upper pole heminephrectomy carries a higher risk of lower pole function loss. Both upper pole heminephrectomy and ureteroureterostomy carry a small risk of additional surgery on the bladder and remnant ureter.

Cost and radiation exposure in the workup of febrile pediatric urinary tract infections.

BACKGROUND: Technetium-99m dimercaptosuccinic acid (DMSA) scans are often used in the evaluation of pediatric patients with febrile urinary tract infections (UTIs). Given the prevalence of febrile UTIs, we sought to quantify the cost, radiation exposure, and clinical utility of DMSA scans when compared with dedicated pediatric renal ultrasounds (RUSs). MATERIALS AND METHODS: An institutional review board approved retrospective study of children under the age of 18 years evaluated at our institution for febrile UTIs between the years 2004-2013 was conducted. The patients had to meet all of the following inclusion criteria: a diagnosis of vesicoureteral reflux, a fever >38°C, a positive urine culture, and evaluation with a DMSA scan and RUS. A chart review was used to construct a cost analysis of technical and professional fees, radiographic results, and radiation dose equivalents. RESULTS: Overall, 104 children met the inclusion criteria. A total of 122 RUS and 135 DMSA scans were performed. The technical costs of a DMSA scan incurred a 35% cost premium as compared to an RUS. The average effective radiation dose of a single DMSA scan was 2.84 mSv. New radiographic findings were only identified on 7% of those patients who underwent greater than 1 DMSA scan. CONCLUSIONS: The utility of the unique information acquired from a DMSA scan as compared to a RUS in the evaluation of febrile UTI must be evaluated on an individual case-by-case basis given the increased direct costs and radiation exposure to the patient.

Use of muscle pedicle flaps for failed bladder neck closure in the exstrophy spectrum.

PURPOSE: The authors have reviewed the use of muscle pedicle flaps for the treatment of failed bladder neck closure in exstrophy spectrum patients. METHODS: A retrospective review of all exstrophy spectrum patients who underwent continence procedures with the use of muscle pedicle flaps at our institution during the last 15 years was performed. Patient characteristics, surgical history, and outcomes, including complications, continence, morbidity, and infection, were assessed. The authors utilized muscle pedicle flaps in eight exstrophy patients, including four patients with classic bladder exstrophy and four patients with cloacal exstrophy. Seven of eight patients had failed at least one prior bladder neck closure, and they had undergone a median of three prior urologic procedures. To achieve continence, five rectus muscle flaps and three gracilis muscle flaps were utilized in combination with bladder neck closure. RESULTS: There were no major intraoperative or postoperative complications. All patients were initially continent, and after a median follow-up of 18.7 months seven of eight patients were continent. One patient required continent urinary stoma revision and one patient developed perineal incontinence after perineal trauma. No patients required revision of, or additional, continence procedures at the bladder neck. DISCUSSION: The use of pedicle muscle flaps appears to be a safe and feasible option for exstrophy spectrum patients with failed bladder neck closure. Although achieving continence can be difficult in this population, use of muscle flaps and bladder neck closure is a viable and effective option in this challenging subset of patients.

Duplicated Renal Collecting System With Ectopic Ureter in Female Bladder Exstrophy: A Case Report.

Bladder exstrophy is a rare major birth defect which requires specialized surgical care. Associated genitourinary tract anomalies are extremely rare in this population, yet significantly impact surgical planning and outcomes. In this case, a full-term newborn girl with a prenatal diagnosis of classic bladder exstrophy was found to have a complete duplicated left collecting system with an ectopic ureter inserted to urethral plate. The patient underwent modern staged repair of exstrophy with bilateral anterior innominate osteotomies and concomitant ureteral reimplantation-the first reported case of ureteral reimplantation at the time of initial closure in a newborn.