Yield of modern genetic evaluation for patients with proximal hypospadias and descended gonads.

INTRODUCTION AND BACKGROUND: Although the pediatric urologic community has embraced a multidisciplinary genetic and endocrine evaluation for newborns with ambiguous genitalia, this approach has been reserved for the most severe cases of undervirilized 46,XY individuals despite growing evidence that genetic differences are found even in patients whose only genitourinary anomaly appears to be proximal hypospadias. Identifying these genetic differences is vital for counseling patients as they move through puberty to parenthood as well as parents on future pregnancies. OBJECTIVE: The primary objective was to evaluate genetic diagnosis in patients with proximal hypospadias. The authors hypothesized the more sensitive genetic evaluation available in the modern era will reveal a high rate of patients with proximal hypospadias and descended testicles who are found to have a genetic difference, supporting a thorough genetic evaluation in these patients. STUDY DESIGN: A retrospective review was performed of all patients who underwent surgical correction for proximal hypospadias at a single institution from January 1, 2010, to December 31, 2016. Those with midshaft hypospadias were excluded as were patients whose primary surgery was performed at an outside institution. Patient characteristics, including demographics, clinical presentation, genetic evaluation, and referral to a multidisciplinary difference of sex development (DSD) clinic, were collected. The chi-squared test and t-test were used for analysis. RESULTS: There were 112 patients with proximal hypospadias who met the inclusion criteria. Of these, 91 had bilaterally descended testicles, whereas 21 had one or more undescended testicles. Thirty-three percent of patients with isolated proximal hypospadias received genetic testing of some kind, with 24% seen in the multidisciplinary DSD clinic. Four patients had an associated genetic syndrome identified, and 5 had a genetic difference of unknown clinical significance. Overall, 10% of patients with proximal hypospadias and descended testicles had an identifiable genetic difference vs 33% with associated cryptorchidism. Of these, one patient with proximal hypospadias and descended testicles had a genetic difference of known clinical significance that was likely to have been missed in the absence of an evaluation by a geneticist. DISCUSSION AND CONCLUSION: There was a high rate of identifiable genetic differences in patients whose only genitourinary abnormality was proximal hypospadias, especially with the 1% risk of a likely missed diagnosis. These findings support the discussion of a genetic evaluation for all patients with proximal hypospadias, regardless of the testicular location.

Using social media for patient-reported outcomes: A study of genital appearance and sexual function in adult bladder exstrophy patients.

INTRODUCTION: There have been few prior studies on patient-centered outcomes of adults with bladder exstrophy; those performed have been single institution reviews. In collaboration with the Association for the Bladder Exstrophy Communities (ABeC) - an international support network for patients and families living with bladder exstrophy - an anonymous social media survey was performed of patient-reported genital appearance and erectile function. OBJECTIVE: The study evaluated the Penile Perception Score (PPS) and the International Index of Erectile Function (IIEF-15) in adult men with bladder exstrophy. It was hypothesized that scores would be significantly lower than prior reported scores for men without the condition. STUDY DESIGN: After review by an anonymous patient advocate volunteer, the ABeC performed an anonymous online survey using social media. RESULTS: Adult men with bladder exstrophy reported PPS, and satisfaction with penile length and axis that were lower than prior published controls (n = 54, P < 0.05). Orgasmic function, sexual desire, and overall satisfaction were also lower (n = 46, P < 0.05). There was no difference in erectile function or intercourse satisfaction compared to controls. There was an association between PPS and erectile function, intercourse satisfaction, and overall satisfaction (P < 0.05) (Summary Fig.). Respondents identified urinary issues, genital appearance, and sexual function as the three main domains that warranted further research. CONCLUSION: This study found that PPS and IIEF-15 were low in adult men with bladder exstrophy, and worse perception of genital appearance was associated with worse sexual satisfaction. Social media is a novel tool for patient-centered outcomes research, and continued collaboration with patients and patient advocate groups is vital.

Early versus delayed closure of bladder exstrophy: A National Surgical Quality Improvement Program Pediatric analysis.

INTRODUCTION: Delayed closure of bladder exstrophy has become more popular; however, there is limited the evidence of its success. Existing literature focuses on intermediate and long-term outcomes, and short-term postoperative outcomes are limited by the small number of cases and varying follow-up methods. OBJECTIVE: The objectives of the current study were to: 1) compare 30-day complications after early and delayed closure of bladder exstrophy, and 2) evaluate practice patterns of bladder exstrophy closure. STUDY DESIGN: The National Surgical Quality Improvement Program Pediatric (NSQIPP) database from 2012 to 2015 was reviewed for all cases of bladder exstrophy closure. Early closure was defined as surgery at age 0-3 days, and delayed closure was defined as age 4-120 days at time of surgery. Demographic, clinical, and peri-operative characteristics were collected, as were postoperative complications, readmissions, and re-operations up to 30 days. Descriptive statistics were performed, and multivariate linear and logistic regression analyses were performed for salient complications. RESULTS: Of 128 patients undergoing bladder exstrophy closure, 62 were included for analysis, with 44 (71%) undergoing delayed closure. Mean anesthesia and operative times were greater in the delayed closure group, and were associated with more concurrent procedures, including inguinal hernia repairs and osteotomies. The delayed closure group had a higher proportion of 30-day complications, due to a high rate of blood transfusion (57% vs 11%). Wound dehiscence occurred in 6/44 (14%) delayed closures, as compared with 0/18 (0%) early closures. When compared with prior published reports of national data from 1999 to 2010, delayed closure was performed more frequently in this cohort (71% vs 27%). DISCUSSION: The NSQIPP provides standardized reporting of peri-operative characteristics and 30-day complications, allowing a comparison of early to delayed closure of bladder exstrophy across multiple institutions. Assessing short-term risks in conjunction with long-term follow-up is crucial for determining optimal management of this rare but complex condition. CONCLUSION: Delayed closure of bladder exstrophy is performed frequently, yet it carries a high rate of 30-day complications worthy of further investigation. This can be useful in counseling patients and families, and to understand practice patterns across the country.

A critical appraisal of continence in bladder exstrophy: Long-term outcomes of the complete primary repair.

INTRODUCTION: Long-term continence outcomes for patients with bladder exstrophy are lacking in the literature. The complete primary repair of exstrophy (CPRE) is a widely adopted approach that seeks to normalize anatomy at the initial repair, thereby allowing early bladder filling and cycling. Previous reports of continence following CPRE, however, are limited by variable follow-up duration and continence definitions. OBJECTIVE: To assess continence and factors associated with a positive outcome in a cohort of patients following CPRE with long-term follow-up. STUDY DESIGN: A retrospective chart review was conducted of all patients with primary bladder closure using CPRE at the present institution for classic bladder exstrophy from 1990 to 2010. Patients <6 years of age or with an incomplete continence assessment at last follow-up were excluded. Continence was defined as voiding volitionally with dry intervals of ≥3 h, which was consistent with other high-volume series in the literature. RESULTS: Twenty-nine of the 52 patients (56%) were eligible for inclusion. Twelve patients were continent at last follow-up, including seven boys and five girls. Mean follow-up for the entire cohort was 148 months. The Summary table displays comparisons between continent and incontinent patients. Of patients achieving continence, 42% did not require further continence operations, while 17% required only one additional continence operation. DISCUSSION: Long-term CPRE continence rates were lower than previously reported, but comparable to other series in the literature. Of those achieving continence, 59% will do so with zero or one additional operation. Sex and osteotomy status were not associated with continence outcomes, although age at follow-up was a predictor of continence, favoring older patients in the present series. The study was limited by lack of standardized, patient-reported continence outcomes and by the retrospective nature of the review. However, the data add to the literature of long-term continence outcomes and are important for counseling families both at initial repair and follow-up. CONCLUSIONS: Complete primary repair of exstrophy can achieve continence without additional operations in a subset of patients. Some patients, however, may not achieve continence until adolescence, underscoring the need for long-term urologic follow-up in patients with bladder exstrophy.

Male infertility in long-term survivors of pediatric cancer: a report from the childhood cancer survivor study.

PURPOSE: The purpose of this study was to assess the prevalence of male infertility and treatment-related risk factors in childhood cancer survivors. METHODS: Within the Childhood Cancer Survivor Study, 1,622 survivors and 274 siblings completed the Male Health Questionnaire. The analysis was restricted to survivors (938/1,622; 57.8 %) and siblings (174/274; 63.5 %) who tried to become pregnant. Relative risks (RR) and 95 % confidence intervals (CI) for the prevalence of self-reported infertility were calculated using generalized linear models for demographic variables and treatment-related factors to account for correlation among survivors and siblings of the same family. All statistical tests were two-sided. RESULTS: Among those who provided self-report data, the prevalence of infertility was 46.0 % in survivors versus 17.5 % in siblings (RR = 2.64, 95 % CI 1.88-3.70, p < 0.001). Of survivors who met the definition for infertility, 37 % had reported at least one pregnancy with a female partner that resulted in a live birth. In a multivariable analysis, risk factors for infertility included an alkylating agent dose (AAD) score ≥3 (RR = 2.13, 95 % CI 1.69-2.68 for AAD ≥3 versus AAD <3), surgical excision of any organ of the genital tract (RR = 1.63, 95 % CI 1.20-2.21), testicular radiation ≥4 Gy (RR = 1.99, 95 % CI 1.52-2.61), and exposure to bleomycin (RR = 1.55, 95 % CI 1.20-2.01). CONCLUSION: Many survivors who experience infertility father their own children, suggesting episodes of both fertility and infertility. This and the novel association of infertility with bleomycin warrant further investigation. IMPLICATIONS FOR CANCER SURVIVORS: Though infertility is common, male survivors reporting infertility often father their own children. Bleomycin may pose some fertility risk.