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Objective: To determine the rate of stone formation amongst patients of the exstrophy-epispadias complex with augmentation cystoplasty. We hypothesize that bowel segment choice influences the rate of stone formation after bladder augmentation and the rate of complications from bladder stone surgery., Methods: An IRB-approved institutional database of 1512 exstrophy-epispadias patients was reviewed retrospectively. Patients that had a history of bladder augmentation and were seen at our institution between 2003 and 2023 were included., Results: Out of 259 patients, bladder stones developed in 21.6% (56), of which the bowel segment used was colon in 147 patients and ileum in 100. Stones formed in 19% of colon augments compared to 29% ileal augments, however, this was not statistically significant (P = .07). The most common primary stone component was dahllite, followed by struvite for all augments (Table 1). The median time to stone treatment after augmentation was 4.14 years (0.75-31). Seventy-four percentage of patients had a recurrence that required a second surgery. The median time from first to second surgery and second to third surgery was 1.4 years and 2.22 years, respectively. Bladder stone surgery complications occurred in 14% of patients, vesicocutaneous fistula being the most common, and complications did not differ by augment type. Median follow-up after first stone intervention was 6.07 years (0-19.5)., Conclusion: The treatment of bladder stones in the exstrophy-epispadias complex remains challenging. Interventions to prevent recurrence are crucial as the majority of patients will require 2 or more stone surgeries in their lifetime., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

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., (© 2023 Wiley Periodicals LLC.)

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.

Background: It has been posited that the osseous pelvic anomalies seen in patients with classic bladder exstrophy (CBE) result from disruption of the pubic symphysis. This hypothesis, however, has not been tested. In the present animal study, our objective was to determine whether the tension of the pubic symphysis helps maintain the shape of the pelvic ring, or whether the growing bones maintain a ring shape even without the tension of the symphysis., Methods: In total, 12 neonatal New Zealand White rabbits underwent pubic symphysiotomy (experimental group, n=9) or sham surgery (control group, n=3) on days 3 or 4 of life. Rabbits were scanned with cone-beam computed tomography at 1, 4, 12, and 20 weeks postoperatively to monitor changes in the following pelvic parameters, which are known to be altered in CBE: anterior segment angle, anterior segment length, intertriradiate distance, interpubic distance, and posterior segment angle. Changes within the experimental and control groups were evaluated using repeated-measures analysis of variance and post hoc Tukey honest significant difference testing. Two-tailed t tests were used to compare treatment groups at each time point., Results: Both groups showed increases in anterior segment length and intertriradiate distance during the study period; rabbits in the experimental group also showed a steady increase in interpubic distance (F=43.9; P<0.001). Experimental rabbits had significantly larger mean values for anterior segment angle, intertriradiate distance, interpubic distance, and posterior segment angle than did control rabbits at all time points. We found no difference in mean anterior segment length between control and experimental groups at any time point. The difference in interpubic distance was particularly pronounced by 20 weeks (experimental group, 13±2.7 mm; control group, 1.1±0.1 mm; P<0.001)., Conclusions: The pubic symphysis is essential for normal pelvic development. Its absence led to early pelvic angulation and progressive pubic separation in a rabbit model. However, we found no significant difference in the mean anterior segment length, and it is likely that other factors are also implicated in the growth disturbance seen in CBE., Level of Evidence: Level V., Competing Interests: E.C. discloses grant support from National Institute on Aging (non–study-related). P.D.S. discloses personal fees from DePuy Synthes, Globus Medical, OrthoPediatrics, and the Journal of Bone and Joint Surgery (all non–study-related). The remaining authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purposes: (1) To understand the concept of workplace cyberbullying, (2) to develop a conceptual definition of workplace cyberbullying, and (3) to examine evidence on workplace cyberbullying in nursing., Method: Walker and Avant's eight-step approach to concept analysis was used., Data Source: Fifteen articles were derived from search of five databases using key terms and factored as cyber, bullying, work, place, and combined terms with nursing or harassment., Findings: Four defining attributes of workplace cyberbullying identified are persistent unwanted act stemming from the work environment, delivered through digital technology, faceless perpetrator, and boundaryless. A new conceptual definition of workplace cyberbullying is developed., Conclusion: Developing a new conceptual definition of workplace cyberbullying is critical, which may be the starting point to theory and new instrument development to test the operational concepts. More research such as using a hybrid approach to develop the concept of workplace cyberbullying., (© 2020 Wiley Periodicals LLC.)

Purpose: Closure of bladder exstrophy is one of the most complex reconstructive procedures. Basic concepts of these operations, as well as their subtle nuances, require years of experience. However, the volume of these cases is low. The authors describe the experience of a junior surgeon learning the details of exstrophy closure during fellowship and her initial career., Methods: Fellows graduating in 2014 were surveyed for their exstrophy experience during fellowship and the following four years. Operative logs of the junior faculty member were reviewed during the same time. Average operative times were calculated for each year., Results: Seventeen of the 25 fellows responded to the survey. Eight surgeons did one or fewer exstrophy closures during fellowship; 14 did one or fewer closures as an attending. The junior faculty member assisted in 18 closures as a fellow and 48 exstrophy closures during the next four years. Average operative time decreased from 485 to 309 min from attendingship year one to four., Conclusions: There are subtle details inside and outside of the operating room required to ensure a successful outcome in this important step of exstrophy reconstruction. Working alongside senior colleagues is essential to allow the junior surgeon to ascend this ladder of mastering exstrophy closure., Type of Study: Diagnostic., Level of Evidence: V., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: A failed closure of classic bladder exstrophy (CBE) has a negative long-term impact on the patient and the health care system., Objective: To investigate the outcomes of CBE patients with failed primary bladder closure., Design, Setting, and Participants: A database of 1317 exstrophy-epispadias complex patients was retrospectively reviewed for CBE patients with failed primary bladder closure from 1965 to 2017 with subsequent repeat closure., Intervention: Repeat bladder exstrophy closure and subsequent continence procedure., Outcome Measurements and Statistical Analysis: Failed exstrophy closures are defined as occurrence of bladder prolapse, dehiscence, vesicocutaneous fistula, outlet obstruction, or combination of these factors. Successful repeat closures are defined as closures that require no further operative intervention as a consequence of these factors. Kaplan-Meier to determine time to successful repeat closure and receiver operator characteristic curve to determine the optimal time for secondary closure were determined., Results and Limitations: In total, 170 CBE patients had at least one repeat closure following a failed primary closure (115 male/55 female). With continued closure attempts, 166/170 (97.6%) patients were successfully closed. The median time to successful closure from birth was 12.9 mo (95% confidence interval: 11.7-15.7). Furthermore, 52/153 (34%) patients had more than one osteotomy. Of 215 total osteotomies, 50 (29.4%) were performed during the 170 failed primary closures, 128 (75.3%) during the 170second closures, and 27 (64.3%) during the 42 third closures. Of 96 patients with available continence data, 74 (77.1%) achieved urinary continence., Conclusions: A successful repeat closure is possible, especially when used in conjunction with a pelvic osteotomy. Continent urinary diversion yielded the highest continence rate in this cohort., Patient Summary: We looked at outcomes of classic bladder exstrophy closure in a large population. Successful repeat closure is possible in the majority of cases when used with pelvic osteotomy. A majority of patients achieved urinary continence using a continent diversion., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose of Review: The exstrophy-epispadias complex (EEC) represents a group of congenitally acquired malformations involving the musculoskeletal, gastrointestinal, and genitourinary systems. Classic bladder exstrophy (CBE) is the most common and best studied entity within the EEC. In this review, imaging features of CBE anatomy will be presented with surgical correlation., Recent Findings: Magnetic resonance imaging (MRI) has emerged as a useful modality for pre- and postnatal assessment of the abdominal wall, pelvic floor, and gastrointestinal and genitourinary systems of children with CBE. The authors' experience supports use of preoperative MRI, in conjunction with navigational software, as a method for identifying complex CBE anatomy. Imaging facilitates surgical approach and improves visualization of complex anatomy, potentially helping to avoid complications. Continued investigation of imaging guidance in CBE repair is needed as surgical techniques improve.

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.)

Objective: To evaluate human acellular dermis (HAD) as an adjunct during bladder neck transection (BNT) by comparing surgical outcomes with other types of tissue interposition., Methods: A prospectively maintained institutional database of exstrophy-epispadias complex (EEC) patients was reviewed for those who underwent a BNT with at least 6 months follow-up. The primary outcome was the occurrence of BNT-related fistulas., Results: In total, 147 EEC patients underwent a BNT with a mean follow-up time of 6.9 years (range 0.52-23.35 years). There were 124 (84.4%) classic exstrophy patients, 22 (15.0%) cloacal exstrophy patients, and 1 (0.7%) penopubic epispadias patient. A total of 12 (8.2%) BNTs resulted in fistulization, including 4 vesicoperineal fistulas, 7 vesicourethral fistulas, and 1 vesicovaginal fistula. There were 5 (22.7%) fistulas in the cloacal exstrophy cohort and 7 (5.6%) fistulas in the classic bladder exstrophy cohort (P = .019). Using either HAD or native tissue flaps resulted in a lower fistulization rate than using no interposed layers (5.8% vs 20.8%; P = .039). Of those with HAD, the use of a fibrin sealant did not decrease fistulization rates when compared to HAD alone (6.5% vs 8.8%, P = .695). There was no statistical difference in surgical complications between the use of HAD and native flaps (8.6% vs 5%, P = .716)., Conclusion: Use of soft tissue flaps and HAD is associated with decreased fistulization rates after BNT. HAD is a simple option and an effective adjunct that does not require harvesting of tissues in patients where a native flap is not feasible., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the state of autophagy and its interactions with apoptosis and cell proliferation in patients who underwent successful early closure or delayed closure of exstrophy. They compared those outcomes with cell culture samples from patients with vesicoureteral reflux as control., Patients and Methods: Primary cultures of bladder smooth muscle cells (SMCs) were established from patients with successful neonatal bladder closure (group 1, N = 5), delayed closure because of small bladder template (group 2, N = 5), and vesicoureteral reflux as control (group 3, N = 5). The myogenicity of the cultures was determined using anti-Desmin antibody. Immunostainings for LC3 to assess autophagy and Ki67 to assess cell proliferation were applied. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick-end labeling assay., Results: Autophagy marker (LC3) expression was significantly higher in the delayed closure group than in the other groups, whereas no significant difference was noted between the neonatal closure and the control groups. Apoptotic indices of the SMCs were remarkably higher in SMC cultures from the delayed closures than in the neonatal closure and the control groups. A significantly lower expression of proliferation marker (Ki67) in the delayed closure group compared with the control and the neonatal closure group was also of note., Conclusion: Patients with small bladder template and delayed closure showed upregulated autophagic process and increased apoptotic indices while experiencing a dramatic decrease in the proliferation of their bladder SMCs. Finally, the concept of manipulating autophagy may lead to promising outcomes for patients with bladder exstrophy in the future., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate corporal tissue viability and changes in endothelial content following current techniques used for epispadias repair in an animal model., Materials and Methods: Sixty rabbits were allocated into 3 groups: sham operation (penile degloving), complete disassembly model, and Cantwell-Ransley model. On weeks 2, 4, 12, and 24 postoperation, the penile tissue was harvested and processed for (1) Masson's trichrome staining for smooth muscle cell (SMC)-to-collagen ratios, (2) immunohistochemical staining for endothelial factor (CD31), and transforming growth factor beta 1 (TGF-β1) (3) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) assay to detect apoptosis., Results: Masson trichrome staining of corporal tissue showed significant decrease in SMC-to-collagen ratio in complete disassembly group compared with sham operation group. The expression of CD31 was significantly lower (P <.05) in complete disassembly group compared with the other groups at all time points, whereas no significant difference was observed between the Cantwell-Ransley group and the sham operation group. Moreover, apoptotic index was markedly higher in the complete disassembly group compared with the 2 other operation groups (P <.05). Immunohistochemistry also showed a significantly higher expression of TGF-β1 in the penile tissue after complete disassembly than Cantwell-Ransley or sham operation., Conclusion: Complete detachment of the urethra from the corpus cavernosa may result in endothelial dysfunction, alteration of SMC content of erectile tissue, and replacement of the native cavernosal tissue with fibrotic tissue. An increased expression of TGF-β1, following the complete disassembly technique, might be one of the important factors causing the abovementioned alterations., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: This study examines a large single-institution experience with cloacal exstrophy patients, analyzing patient demographics and surgical strategies predictive of bladder closure outcomes., Methods: One hundred patients with cloacal exstrophy were identified. Complete closure history including demographics, operative history, and outcomes was available on 60 patients. Twenty-six patients with a history of failed initial bladder closure were compared to 34 with a history of successful initial bladder closure. Univariate logistic regression analysis was used to compare the two groups., Results: Median follow up time after initial closure was 9years (range: 13months-29years). A 1cm increase in pre-closure diastasis resulted in a 2.64 increase in the odds of initial closure failure (p=0.004). Protective strategies against failure included delaying closure (per month) (OR=0.894, p=0.009), employing pelvic osteotomies (OR=0.095, p<0.001), and applying external fixation (OR=0.024; p=0.001). Among patients who underwent osteotomy (31% of patients in the failed group, 82% in the successful group), a longer delay between osteotomy and closure (OR=0.033; p=0.005) was also protective against failure., Conclusion: Patients with a large diastasis are more likely to fail initial closure. Delaying initial closure for at least 3months, performing pelvic osteotomy, and using an external fixation device post-operatively are strategies that improve closure success., (Published by Elsevier Inc.)

The exstrophy-epispadias complex is a rare congenital malformation of the genitourinary system, abdominal wall musculature, and pelvic bones. Historically, surgical outcomes in patients with classic bladder exstrophy, the most common presentation of the exstrophy-epispadias complex, were poor. However, modern techniques have increased the success of achieving urinary continence, satisfactory cosmesis, and improved quality of life. Still, recent studies recognize complications that may occur during management of these patients. This review provides readers with an overview of the exstrophy-epispadias complex, the modern management of bladder exstrophy, and potential surgical complications.