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Background: Management of the adolescent varicocele focuses on optimizing fertility potential, but to date there is limited data on the success of varicocelectomy on optimizing semen parameters for individual adolescent patients. We reviewed our database of over 1600 adolescent varicocele patients to find those with pre- and postoperative semen analyses to determine the impact of varicocele correction., Methods: 15 Tanner stage V patients with unilateral clinically apparent left-sided with pre- and postoperative semen analyses were identified. Mixed models were used to compare semen parameters pre- and post-varicocelectomy in patients with successful management., Results: Complete elimination of the varicocele was achieved in 12/15 (80%) patients. Three patients had persistent varicocele (with down-grading in two) and declined further intervention. Median time between pre- and postoperative semen analyses was 24.2 months. For those with successful varicocele correction, total motile sperm count (TMSC) improved in all but one (Figure 1), with an average increase of 44.0 million (95% CI: 18.7-69.3) in post-varicocelectomy analyses compared to pre-varicocelectomy (p = 0.0016). Mean percent improvement was 649.2%. It went from abnormal to normal (≥20 million/cc) in 55.6% (5/9). For the three patients with persistent varicocele, one had improved TMSC from abnormal to normal range, one had worsening within normal range, and one had effectively no change., Conclusion: Successful correction of adolescent varicocele may improve TMSC. In over half of our institution's cases, an abnormal value normalized. Surgical intervention may be considered for adolescent varicoceles associated with abnormal semen parameters., Levels of Evidence: Level III., Type of Study: Treatment study., Competing Interests: Conflicts of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There is limited quality of evidence regarding the accuracy of contrast-enhanced voiding urosonography (ceVUS) for diagnosis of vesicoureteral reflux (VUR) compared to fluoroscopic voiding cystourethrography (VCUG), and minimal data on the use of the ultrasound contrast agent Optison™ for this purpose., Objective: To compare the accuracy of ceVUS using Optison™ to VCUG, and to assess inter-rater agreement regarding presence and grading of VUR., Study Design: In this retrospective investigation, all sequential ceVUS with Optison™ and VCUG studies performed in children between 2014 and 2017 were reviewed. Two raters independently graded all ceVUS studies using a 5-point scale. CeVUS sensitivity and specificity were estimated separately for each rater using the VCUG report as the ground truth for presence and degree of VUR. Logistic and ordinary linear regression models assessed rater-report agreement and inter-rater agreement for each kidney, Optison™ dose, and referral diagnosis., Results: 97 children (51 females) with 101 paired studies were included. Sensitivity and specificity of ceVUS for VUR detection were identical for both raters: right kidney 75%/90.9%; left kidney 85.7%/78.9% (Figure). There was no statistically significant difference in disagreement between raters and the VCUG report for the right or left kidney. Inter-rater agreement on ceVUS grading was 90% and 88% for right and left kidneys, respectively. There was a significant negative association between fetal hydronephrosis vs urinary tract infection and disagreement between Rater 2 and the VCUG report for the left kidney. There were no other significant associations with respect to either kidney, Optison™ dose, or referral diagnosis., Discussion: Our study showed that detection of VUR with ceVUS and Optison™ is comparable to fluoroscopic VCUG. Based on the VCUG reports, the incidence of VUR in our patient population was substantially lower than in the meta-analysis of Chua et al. and in the study of Kim et al. The explanation for the large discrepancy in VUR incidence may reflect differences in the patient populations, and in our reporting of VUR with respect to kidney number rather than to pelviureteral units. Study limitations include its retrospective nature and potential bias in terms of patient selection. Since VUR is an intermittent phenomenon, sequential rather than simultaneous performance of the ceVUS and fluoroscopic studies might have influenced VUR detection., Conclusion: A blinded comparison of ceVUS performed with Optison™ to fluoroscopic VCUG showed moderate-good sensitivity and specificity for diagnosis of VUR., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Judicious use of antibiotics for surgical prophylaxis is important for reducing antimicrobial resistance while preventing infectious surgical complications. In the setting of pediatric distal hypospadias repairs, it is unclear if antibiotic surgical prophylaxis is beneficial., Objective: The purpose of this study was to compare rates of infectious complications in pediatric subjects undergoing distal hypospadias repair who received any peri-operative antibiotics to those who did not., Study Design: This was a review of a retrospective cohort from a database of individuals undergoing hypospadias repairs evaluating whether they received peri-operative or post-operative antibiotic prophylaxis and determining the rate of infectious complications in those who did compared to those who did not receive antibiotic prophylaxis. Infectious complications were defined as surgical site infection (SSI) or urinary tract infection (UTI)., Results: There was no significant difference in infectious complication rates between individuals who received peri-operative parenteral antibiotic prophylaxis and those who did not. All subjects with infectious complications received post-operative oral antibiotic prophylaxis. There was one instance of C. difficile infection in a subject who received peri-operative parenteral antibiotics., Discussion: Reducing antibiotic utilization without increasing infectious surgical complications is important in safely reducing antimicrobial resistance. In this study of pediatric distal hypospadias repair, peri-operative antibiotics did not demonstrate a clear benefit and post-operative oral antibiotics demonstrated no benefit in preventing infectious complications. Other studies evaluating peri- and post-operative antibiotics for pediatric hypospadias repair have also failed to demonstrate a benefit for antibiotics in preventing infections. Practitioners should reconsider the use of antibiotics in this setting., Conclusion: Routine antibiotic prophylaxis does not appear beneficial for preventing infectious complications following uncomplicated, stented pediatric distal hypospadias repairs., Competing Interests: Conflicts of interest KMD owns stock in Merck and Organon&Co. Otherwise we have no conflicts of interest to disclose., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Study Objective: Infants with genital development considered atypical for assigned female sex may undergo feminizing genitoplasty (clitoroplasty and/or vaginoplasty) in early life. We sought to identify factors associated with parent/caregiver decisions regarding genitoplasty for their children with genital virilization., Design: Longitudinal, observational study SETTING: Twelve pediatric centers in the United States with multidisciplinary differences/disorders of sex development clinics, 2015-2020 PARTICIPANTS: Children under 2 years old with genital appearance atypical for female sex of rearing and their parents/caregivers INTERVENTIONS/OUTCOME MEASURES: Data on the child's diagnosis and anatomic characteristics before surgery were extracted from the medical record. Parents/caregivers completed questionnaires on psychosocial distress, experience of uncertainty, cosmetic appearance of their child's genitalia, and demographic characteristics. Urologists rated cosmetic appearance. For 58 patients from the study cohort with genital virilization being raised as girls or gender-neutral, we compared these data across 3 groups based on the child's subsequent surgical intervention: (i) no surgery (n = 5), (ii) vaginoplasty without clitoroplasty (V-only) (n = 15), and (iii) vaginoplasty and clitoroplasty (V+C) (n = 38)., Results: Fathers' and urologists' ratings of genital appearance were more favorable in the no-surgery group than in the V-only and V+C groups. Clitorophallic length was greater in the V+C group compared with the V-only group, with substantial overlap between groups. Mothers' depressive and anxious symptoms were lower in the no-surgery group compared with the V-only and V+C groups., Conclusions: Surgical decisions were associated with fathers' and urologists' ratings of genital appearance, the child's anatomic characteristics, and mothers' depressive and anxious symptoms. Further research on surgical decision-making is needed to inform counseling practices., (Copyright © 2022. Published by Elsevier Inc.)

Background: Both the development of kidney function in healthy children and autoregulation ability of kidney function in patients with asymmetric kidneys are important in clinical diagnosis and treatment of kidney-related diseases, but there are however only limited studies. This study aimed to investigate development of kidney function in normal children with healthy symmetric kidneys and autoregulation of the healthy kidney compensating the functional loss of a diseased one in children with asymmetric kidneys., Methods: Two hundred thirty-seven children (156 male, 81 female) from 0 to 20y (average 4.6y ± 5.1) undergoing 99m Tc-MAG3 renography were included, comprising 134 with healthy symmetrically functioning kidneys and 103 with asymmetric kidneys. Clearance was calculated from kidney uptakes at 1-2 min. A developmental model between MAG3 clearance (CL) and patient age in normal group was identified (CL = 84.39Age 0.395  ml/min, r = 0.957, p < 0.001). The clearance autoregulation rate in abnormal group with asymmetric kidneys was defined as the ratio of the measured MAG3 clearance and the normal value predicted from the renal developmental model of normal group., Results: No significant difference of MAG3 clearance (p = 0.723) was found between independent abnormal group and normal group. The autoregulation rate of kidney clearance in abnormal group was 94.2% on average, and no significant differences were found between two age groups (p = 0.49), male and female (p = 0.39), and left kidney and right kidney (p = 0.92) but two different grades of asymmetric kidneys (p = 0.02)., Conclusions: The healthy kidney of two asymmetric kidneys can automatically regulate total kidney function up to 94% of two symmetric kidneys in normal children., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Objective: The impact of parent-reported stigma due to their child's disorder/difference of sex development (DSD) on parent psychosocial adjustment is poorly understood. In other pediatric populations, perceived interference of medical conditions into daily activities (i.e., illness intrusiveness ) mediates the relationship of stigma to adjustment. This study assessed relationships between parent-focused and child-focused stigma → illness intrusiveness → depressive and anxious symptoms . Exploratory analyses sought to identify patient characteristics associated with stigma., Method: Caregivers (59 women and 43 men) of 63 children diagnosed with a DSD up to age 4 years completed measures of demographics, parent-focused and child-focused stigma, illness intrusiveness, and depressive and anxious symptoms., Results: Increased parent-focused and child-focused stigma were associated with increased illness intrusiveness, which, in turn, was associated with increased depressive and anxious symptoms for parents nested within dyads. Among children with DSD family histories, parents reported greater child-focused stigma., Conclusion: Parents who experience DSD-related stigma report greater interference of their child's DSD into their daily activities, which is associated with poorer psychosocial adjustment. Findings support developing clinical interventions related to parents' perceptions of stigma and illness intrusiveness to improve parent adjustment., Competing Interests: Disclosure: P. F. Austin is a clinical investigator and member of the pediatric advisory group for Allergan. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This report reviews the various techniques for vaginal obliterative surgery in the transmasculine patient population, including advantages and drawbacks with differing methods and reflects on the focus of future research and surgical efforts., Findings: Existing techniques for vaginal obliterative surgery by vaginectomy or colpocleisis vary without strong evidence to identify a superior approach., Summary: The increasing number of transmasculine patients seeking vaginectomy as a part of gender-affirming surgery must be matched by evidence-based techniques that provide a safe, long-term outcome., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2022 American Urogynecologic Society. All rights reserved.)

Purpose: To determine the prevalence of prostatic metaplasia in an expanded cohort of transmasculine individuals undergoing gender-affirming resection of vaginal tissue., Methods: Institutional Review Board approval was obtained. Clinical records were reviewed for all transmasculine individuals undergoing vaginal tissue resection at our institution between January 2018 and July 2021. Corresponding pathology specimens were examined grossly and microscopically, including immunohistochemical stains for NKX3.1, prostate-specific antigen (PSA), and androgen receptor (AR). Vaginal specimens from three patients without androgen supplementation were used as controls., Results: Twenty-one patients met inclusion criteria. The median age at surgery was 26.4 years (range 20.6-34.5 years). All patients had been assigned female gender at birth and lacked endocrine or genetic abnormalities. All were on testosterone therapy; median duration of therapy at surgery was 4.4 years (range 1.4-12.1 years). In the transmasculine group, no gross lesions were identified. Microscopically, all specimens demonstrated patchy intraepithelial glandular proliferation along the basement membrane and/or nodular proliferation of prostate-type tissue within the subepithelial stroma. On immunohistochemical staining, performed for a subset of cases, the glandular proliferation was positive for NKX3.1 (16/16 cases; 100%), PSA (12/14 cases; 85.7%), and AR (8/8 cases; 100%). Controls showed no evidence of prostatic metaplasia., Conclusion: One hundred percent of vaginal specimens obtained from transmasculine individuals on testosterone therapy (21/21 cases) demonstrated prostatic metaplasia. Further investigation is warranted to characterize the natural history and clinical significance of these changes. Patients seeking hormone therapy and/or gender-affirming surgery should be counseled on the findings and their yet-undetermined significance., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Caregivers of female infants with congenital adrenal hyperplasia (CAH) often confront complex medical decision-making (e.g., early feminizing genitoplasty)., Objective: This study aimed to evaluate the relevant medical decisions and subsequent decisional regret of caregivers following their child's genitoplasty., Study Design: Caregivers (N = 55) were recruited from multidisciplinary treatment programs for participation in a longitudinal study. Qualitative data was collected at 6-12 months following feminizing genitoplasty to evaluate caregiver-reported decision points across their child's treatment. Quantitative exploratory analysis evaluated pre-operative predictors of subsequent decisional regret., Discussion: When prompted about their decision-making and potential regret, most caregivers (n = 32, 80%) reported that their daughter's genital surgery was their primary medical decision. Specific themes regarding genital surgery included the timing and type of surgery. Most caregivers reported no decisional regret (62%), with 38% reporting some level of regret. Greater pre-operative illness uncertainty predicted heightened decisional regret at follow-up, p = .001., Conclusion: Two-thirds of caregivers of female infants with CAH reported not regretting their decision-making. Nevertheless, over one-third of caregivers reported some level of regret, suggesting the need for improvements in shared decision-making processes. Many, but not all, families reported that this regret was related to surgical decision-making. Reducing caregiver illness uncertainty (e.g., providing clear information to families) may increase their satisfaction with decision-making. Further research is needed to determine how the evolving care practices surrounding early genitoplasty will impact families., Competing Interests: Conflicts of interest Dr. Nokoff has previously consulted for Antares Pharma, Inc. The authors have no other conflicts of interest to disclose., (Copyright © 2021 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Subclinical varicocele represents an abnormality of veins of the pampiniform plexus on scrotal ultrasound (US) without a clinically palpable varicocele. Its significance remains unclear. While guidelines do not recommend surgical intervention, clinical management is variable. As there is limited information on long-term outcome of subclinical varicoceles due to challenges in diagnosis and management, we performed a single-institution, retrospective review of patients from October 1999 to October 2014 with subclinical varicocele and with available US studies reviewed by a single radiologist. Subclinical varicocele was defined as dilation of the pampiniform venous plexus on US involving ≥2 vessels with diameter >2.5 mm, without clinical varicocele on physical examination or prior inguinal surgery. Thirty-six of 98 patients identified were confirmed as having a subclinical varicocele and analyzed. The mean age at initial visit was 15.5 years, with a mean follow-up of 26.5 months. The majority were right-sided (69.4%, n = 25), usually with a contralateral clinical varicocele. Testicular asymmetry (>20% volume difference of the affected side by testicular atrophy index formula) was assessed in 9 patients with unilateral subclinical varicocele without contralateral clinical or subclinical varicocele and observed in 1 patient. Of 17 patients with follow-up, 3 (17.6%) progressed to clinical varicocele without asymmetric testicular volume, as most remained subclinical or resolved without surgery. In our experience, subclinical varicoceles appeared unlikely to progress to clinical varicoceles, to affect testicular volume, or to lead to surgery. Although our study is limited in numbers and follow-up, this information may aid clinical management strategies and guide future prospective studies., Competing Interests: None

Objective: This study identifies trajectories of parent depressive symptoms after having a child born with genital atypia due to a disorder/difference of sex development (DSD) or congenital adrenal hyperplasia (CAH) and across the first year postgenitoplasty (for parents who opted for surgery) or postbaseline (for parents who elected against surgery for their child). Hypotheses for four trajectory classes were guided by parent distress patterns previously identified among other medical conditions., Methods: Participants included 70 mothers and 50 fathers of 71 children diagnosed with a DSD or CAH with reported moderate to high genital atypia. Parents were recruited from 11 US DSD specialty clinics within 2 years of the child's birth and prior to genitoplasty. A growth mixture model (GMM) was conducted to identify classes of parent depressive symptoms over time., Results: The best fitting model was a five-class linear GMM with freely estimated intercept variance. The classes identified were termed "Resilient," "Recovery," "Chronic," "Escalating," and "Elevated Partial Recovery." Four classes have previously been identified for other pediatric illnesses; however, a fifth class was also identified. The majority of parents were classified in the "Resilient" class (67.6%)., Conclusions: This study provides new knowledge about the trajectories of depressive symptoms for parents of children with DSD. Future studies are needed to identify developmental, medical, or familial predictors of these trajectories., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: Botulinum neurotoxin A (BoNT/A), or Botox, is a popular option for overactive bladder (OAB) and neurogenic bladder (NGB) with or without incontinence. This review aims to discuss the clinical outcomes of BoNT in adult and pediatric bladder conditions, and introduces the potential benefit of novel, engineered neurotoxins beyond BoNT/A., Recent Findings: A large volume of evidence supports the use of Botox for OAB (to reduce urgency, frequency and incontinence episodes), and for NGB (to decrease incontinence and improve bladder capacity and detrusor pressures). Botox is now also Food & Drug Administration (FDA)-approved for pediatric neurogenic detrusor overactivity. However, urinary retention, diminished response over time and treatment failures are prevalent issues with Botox. Modifying natural BoNTs or forming chimeric toxins are alternatives to BoNT/A that may have higher efficacy and lower side-effect profile. One example is BoNT/BMY-WW. This novel engineered toxin binds to a more commonly expressed synaptotagmin receptor, with potentially more potent paralytic effect and less capacity for systemic diffusion., Summary: Novel engineered neurotoxins may be the next frontier in OAB and NGB therapy., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: There has been an exponential increase in referrals for transmasculine patients seeking genital affirmation surgery. Despite transgender men's equal interest in metoidioplasty and phalloplasty, research has primarily focused on phalloplasty., Aim: To summarize and investigate the relationship between surgical technique, complications, and patient-satisfaction., Methods: We performed a systematic review and meta-analysis of surgical techniques and physician- and patient-reported outcomes of gender-affirming clitoral release and metoidioplasty (PROSPERO# 158722) with literature from PubMed, Google Scholar, and ScienceDirect. Data were extracted using PRISMA guidelines. All searches, extractions, and grading were independently completed by 2 authors., Main Outcome Measures: Main measures were surgical technique, patient satisfaction, voiding, urethral stricture, and urethral fistula., Results and Conclusion: A total of 7 non-overlapping articles on metoidioplasty were identified, with a total of 403 patients. We identified 4 metoidioplasty techniques: Hage, Belgrade, labial ring flap, and extensive metoidioplasty. All techniques included urethral lengthening. The reported neophallus length ranged from 2 cm to 12 cm, with the smallest neophallus occurring with the labial ring flap technique and extensive metoidioplasty the largest. Across techniques, voiding while standing was reported in most patients, with the lowest rate reported with the labial ring flap (67%). Complications were impacted by surgical technique, with the lowest rates of fistula and stricture occurring with the Belgrade technique. Fistula rates ranged from 5% to 37%, while stricture ranged from 2% to 35% of patients. The Belgrade technique reported significantly lower rates of fistula and stricture (P = .000). The patient-reported outcomes were described for the Belgrade technique and extensive metoidioplasty. Both techniques showed high aesthetic and sexual satisfaction. Transgender individuals can achieve an aesthetically and sexually satisfactory neophallus using a variety of metoidioplasty techniques; however, urethral outcomes vary significantly by technique. The Belgrade technique reported the best outcomes, although data remains limited. Patient priorities should be used to determine surgical technique. Jolly D, Wu CA, Boskey ER, et al. Is Clitoral Release Another Term for Metoidioplasty? A Systematic Review and Meta-Analysis of Metoidioplasty Surgical Technique and Outcomes. Sex Med 2021;9:100294., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Disorders/differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. While there remains controversy around the traditionally binary concept of sex, most patients with DSD are reared either male or female depending on their genetic sex, gonadal sex, genital phenotype and status of their internal genital tract. This study uses prospective data from 12 institutions across the United States that specialize in DSD care. We focused on patients raised female. Eligible patients had moderate to severe genital atypia (defined as Prader score >2), were ≤2 years of age at entry, and had no prior genitoplasty. The aim of this study is to describe early post operative complications for young patients undergoing modern approaches to feminizing genitoplasty. Of the 91 participants in the cohort, 57 (62%) were reared female. The majority had congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (n = 52), 1 had ovo-testicular syndrome, 2 had mixed gonadal dysgenesis and 2 had partial androgen insensitivity syndrome (PAIS). Of the 50 participants who received early genitoplasty, 43 (86%) had follow-up at 6-12 months post-surgery. Thirty-two participants (64%) received a clitoroplasty, 31 (62%) partial urogenital mobilization and 4 (8%) total urogenital sinus mobilization. Eighteen percent (9/50) experienced post-surgical complications with 7 (14%) being rated as Clavien-Dindo grade III. Both parents and surgeons reported improved satisfaction with genital appearance of participants following surgery compared to baseline. This information on post-operative complications associated with contemporary approaches to feminizing genitoplasty performed in young children will help guide families when making decisions about whether or not to proceed with surgery for female patients with moderate to severe genital atypia., (Published by Elsevier Ltd.)

Objective: A subset of parents of children with disorders/differences of sex development (DSD) including ambiguous genitalia experience clinically elevated levels of anxious and depressive symptoms. Research indicates that uncertainty about their child's DSD is associated with parent psychosocial distress; however, previous studies have been cross-sectional or correlational in nature. The current study is the first to examine the longitudinal trajectory of the relationship between caregiver-perceived uncertainty about their child's DSD and caregiver anxious and depressive symptoms across the first 12 months following genital surgery in young children, or if surgery was not performed, the first 12 months following study entry., Methods: One hundred and thirteen caregivers (Mage = 32.12; 57.5% mothers; 72.6% Caucasian) of children (N = 70; Mage = 9.81 months; 65.7% female) with DSD were recruited from 12 DSD specialty clinics in the United States. Caregivers completed psychosocial measures at baseline, 6 and 12 months following genitoplasty, or study entry if parents elected not to have surgery for their child., Results: Caregiver illness uncertainty and both anxious and depressive symptoms were highest at baseline and decreased over time (ps < .05). Caregiver illness uncertainty predicted symptoms of anxious and depressive symptoms across all time points (ps < .05)., Conclusions: Caregivers' perceptions of uncertainty about their child's DSD are highest soon after diagnosis, and uncertainty continues to predict both anxious and depressive symptoms across time. Thus, the initial diagnostic period is a critical time for psychological assessment and intervention, with parent illness uncertainty being an important clinical target., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Prostatic-type differentiation in the lower female genital tract is encountered rarely and its causes and clinical associations are not well established. Within the vagina, reports to date have invariably described ectopic prostatic-type differentiation as restricted to the lamina propria. We recently encountered a patient receiving testosterone for gender dysphoria whose vaginectomy specimen showed a prostatic glandular proliferation within the surface epithelium. To elucidate its potential association with androgen exposure, we sought similar lesions, resected over a 26-year period, from patients with exogenous or endogenous androgen excess. Thirteen cases were identified, involving the vagina (n=12) and exocervix (n=1). The most common clinical context was gender dysphoria with long-term testosterone therapy; the lesion was present in 7 of 8 gender-dysphoric patients examined. Four other patients had congenital disorders of sexual development associated with endogenous androgen excess (congenital adrenal hyperplasia, 46,XY disorder of sexual development, and ovotesticular disorder of sexual development). Two had no known exposure to androgen excess. Immunohistochemically, glands stained for NKX3.1 (100% of cases), androgen receptor (100%), CK7 (92%), and prostate-specific antigen (69%). Follow-up (median duration, 11 mo) showed no masses or neoplasia. We propose the designation "androgen-associated prostatic metaplasia" for this form of prostate tissue with distinctive clinical, histologic and immunohistochemical features. It is novel and previously unrecognized within the vagina. It is strikingly prevalent among patients undergoing gender-affirming surgery, an increasingly common procedure. Recognition is important to distinguish it from other potentially neoplastic glandular lesions and facilitate accrual of more follow-up data to better understand its natural history.

Purpose: We evaluated demographic, financial and support predictors of distress for parents of young children with disorders of sex development including atypical genital development, and characterized early parental experiences. This work extends our previous findings to identify those parents at risk for distress., Materials and Methods: Participants included mothers (76) and fathers (63) of a child (78) diagnosed with disorders of sex development characterized by moderate to severe genital atypia. Parents completed a demographic questionnaire, measures of anxious and depressive symptoms, quality of life, illness uncertainty and posttraumatic stress symptoms, and rated their satisfaction with the appearance of their child's genitalia., Results: Depressive and posttraumatic stress symptoms of caregivers were comparable to standardized norms while levels of anxious symptoms were below norms. A subset of parents reported clinically elevated symptoms. Overall 26% of parents reported anxious symptoms, 24% reported depressive symptoms and 17% reported posttraumatic stress symptoms. Levels of illness uncertainty were lower than those of parents of children with other chronic illnesses. Differences by parent sex emerged, with mothers reporting greater distress. Lower income, increased medical care and travel expenses, and having no other children were related to increased psychosocial distress., Conclusions: Early psychosocial screening is recommended for parents of children with disorders of sex development. Clinicians should be aware that financial burden and lack of previous parenting experience are risk factors for distress.

Purpose: Many transgender men seek surgical interventions to create male genitalia. Currently, there is no standardized tool to assess individual goals and expectations for such reconstructive genital surgery. The purpose of this study was to develop and pilot a genital affirmation surgical priorities scale (GASPS) in transgender men seeking metoidioplasty and/or phalloplasty. Methods: The research team developed the GASPS and piloted it with 63 patients seeking reconstructive genital surgery. The scale was constructed after a comprehensive literature review identified key areas of importance, including size, erogenous and tactile sensation, interest in penetrative sex, ability to urinate standing up, and maintenance of orgasmic function. Results were then tabulated and analyzed to look for trends. Results: Sixty three consecutive patients, mean age 24.98 years (standard deviation [SD]=5.87), were administered the assessment. On the 5 point Likert scale, patients were most concerned about being able to stand to urinate (mean=4.38, SD=1.06) and erotic sensation (mean=4.21, SD=0.8). The ability to engage in penetrative intercourse (mean=3.98, SD=1.34), tactile sensation (mean=3.93, SD=1.01), and penis length (mean=3.37, SD=1.18), and girth (mean=3.09, SD=1.20) were not universally considered to be important and responses varied widely. Most patients (86%) stated they had a history of being able to orgasm, and 8% did not know. Feedback suggested that scale use helped patients clarify goals for surgery. Conclusion: GASPS use confirmed the diversity of patient priorities and the importance of individualized goal assessment. It also confirmed previous reports that standing to urinate is a major genital affirmation motivation for many transgender men., Competing Interests: No competing financial interests exist., (© Oren Ganor et al. 2019; Published by Mary Ann Liebert, Inc.)

Objective: The purpose of this study was to assess clinical practice patterns with regard to diagnosis and management of testicular regression syndrome (TRS), a condition in 46,XY males with male phenotypic genitalia and bilateral absence of testes. Methods: A retrospective review was conducted at two large pediatric academic centers to examine diagnostic and management approaches for TRS. Results: Records of 57 patients were reviewed. Diagnostic methods varied widely between patients and included hormonal testing, karyotype, imaging, and surgical exploration, with multiple diagnostic methods frequently used in each patient. Of the 30 subjects that had reached adolescence at the time of the study, 17 (57%) had gaps in care of more than 5 years during childhood. Thirty subjects had received testosterone replacement therapy at a mean age of 12.1 ± 1.0 years. Forty-seven percent had a documented discussion of infertility. Eighty-two percent discussed prosthesis placement, with 35% having prostheses placed. Twenty-three percent were seen by a psychosocial provider. The between-site differences were age at fertility discussion, age at and number of prostheses placed, and type/age of testosterone initiation. Conclusion: Our findings highlight the wide variation in diagnostic approaches, follow-up frequency, testosterone initiation, fertility counseling, and psychosocial support for patients with TRS. Developing evidence-based guidelines for the evaluation and management of TRS would help reduce inconsistencies in care and unnecessary testing. Ongoing follow-up and coordination of care, even during the years when no hormonal treatment is being administered, could lead to opportunities for psychosocial support and improved interdisciplinary approach to care. Abbreviations: AMH = antimüllerian hormone; CAH = congenital adrenal hyperplasia; DSD = differences/disorders of sex development; hCG = human chorionic gonadotropin; TRS = testicular regression syndrome.

Parents of children with disorders of sex development (DSD) report significant psychological distress, including posttraumatic stress symptoms (PTSS), with mothers consistently reporting higher rates of psychological distress than fathers. However, psychological factors contributing to PTSS in both parents are not well understood. The present study sought to fill this gap in knowledge by examining PTSS and illness uncertainty, a known predictor of psychological distress, in parents of children recently diagnosed with DSD. Participants were 52 mothers (M age  = 32.55 years, SD = 5.08) and 41 fathers (M age  = 35.53 years, SD = 6.78) of 53 infants (M age  = 9.09 months, SD = 6.19) with DSD and associated atypical genital development. Participants were recruited as part of a larger, multisite study assessing parents' psychosocial response to their child's diagnosis of DSD. Parents completed measures of illness uncertainty and PTSS. Mothers reported significantly greater levels of PTSS, but not illness uncertainty, than fathers, and were more likely than fathers to report clinical levels of PTSS (21.2% compared to 7.3%). Hierarchical regression revealed that parent sex, undiagnosed or unclassified DSD status, and illness uncertainty were each associated with PTSS. The overall model accounted for 23.5% of the variance associated with PTSS. Interventions targeting illness uncertainty may be beneficial for parents of children with newly diagnosed DSD.

As part of establishing a gender surgery center at a pediatric academic hospital, we undertook a process of identifying key ethical, legal, and contextual issues through collaboration among clinical providers, review by hospital leadership, discussions with key staff and hospital support services, consultation with the hospital's ethics committee, outreach to other institutions providing transgender health care, and meetings with hospital legal counsel. This process allowed the center to identify key issues, formulate approaches to resolving those issues, and develop policies and procedures addressing stakeholder concerns. Key issues identified during the process included the appropriateness of providing gender-affirming surgeries to adolescents and adults, given the hospital's mission and emphasis on pediatric services; the need for education on the clinical basis for offered procedures; methods for obtaining adequate informed consent and assent; the lower and upper acceptable age limits for various procedures; the role of psychological assessments in determining surgical eligibility; the need for coordinated, multidisciplinary patient care; and the importance of addressing historical access inequities affecting transgender patients. The process also facilitated the development of policies addressing the identified issues, articulation of a guiding mission statement, institution of ongoing educational opportunities for hospital staff, beginning outreach to the community, and guidance as to future avenues of research and policy development. Given the sensitive nature of the center's services and the significant clinical, ethical, and legal issues involved, we recommend such a process when a establishing a program for gender surgery in a pediatric institution., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Purpose: Little is known about the phenotypes, diagnoses, and sex of rearing of infants with atypical genital development in the United States. As part of a multicenter study of these infants, we have provided a baseline report from US difference/disorder of sex development clinics describing the diagnoses, anatomic features, and sex of rearing. We also determined whether consensus guidelines are followed for sex designation in the United States., Methods: Eligible participants had moderate-to-severe genital atypia, were aged <3 years, and had not undergone previous genitoplasty. Karyotype, genetic diagnosis, difference/disorder of sex development etiology, family history, and sex of rearing were collected. Standardized examinations were performed., Results: Of 92 subjects, the karyotypes were 46,XX for 57%, 46,XY for 34%, and sex chromosome abnormality for 9%. The median age at the baseline evaluation was 8.8 months. Most 46,XX subjects (91%) had congenital adrenal hyperplasia (CAH) and most 46,XY subjects (65%) did not have a known diagnosis. Two individuals with CAH underwent a change in sex of rearing from male to female within 2 weeks of birth. The presence of a uterus and shorter phallic length were associated with female sex of rearing. The most common karyotype and diagnosis was 46,XX with CAH, followed by 46,XY with an unknown diagnosis. Phenotypically, atypical genitalia have been most commonly characterized by abnormal labioscrotal tissue, phallic length, and urethral meatus location., Conclusions: An increased phallic length was positively associated with rearing male. Among the US centers studied, sex designation followed the Consensus Statement recommendations. Further study is needed to determine whether this results in patient satisfaction.

Introduction: A central ethical dilemma in management of the patient with a disorder of sex development (DSD) is the potential conflict between respect for the fundamental right of the child for physical and emotional integrity and self-determination, and the right of parents to serve as surrogate decision-makers and act in their child's best interest., Methods: Over the past 2 years we have encountered three complex DSD cases on the spectrum of mixed gonadal dysgenesis to ovotesticular DSD in which gender assignment and therefore optimal surgical management was uncertain. All patients had mosaic karyotypes with Y chromosome, dysgenetic ovary and dysgenetic testis, a urogenital sinus, and prominent phallus. In all three cases a team approach was taken to assess functional potential and risks along either gender pathway and to develop a spectrum of treatment options for parental consideration, including: 1. masculinization with removal of dysgenetic ovary; 2. initial vaginoplasty but with retention of the phallus (±bilateral gonadectomy); 3. initial vaginoplasty with "burial" of corporal bodies (Pippi Salle procedure) (±bilateral gonadectomy); 4. full feminization: vaginoplasty and clitoroplasty (with bilateral gonadectomy); 5. no surgical intervention., Results: In all three cases, after consideration of risks and benefits of all options, parents selected option 2: gonadectomy to eliminate tumor risk and vaginoplasty, taking advantage of the child's young age to exteriorize urinary and reproductive tracts to avoid incontinence and infection and supporting parental bias toward female gender, but preservation of phallic structures to ensure a male option should the patient later declare a male gender identity. Parents of the three patients were contacted post-operatively (at 7, 17, and 22 months) for follow-up. All (3/3) regarded their child's development and wellbeing positively, and their own decisions regarding gender assignment and surgical plan favorably. All (3/3) regarded the team advisory process as balanced and supportive., Conclusion: In the setting of exposure of the neonatal brain to testosterone, vaginoplasty and phallic preservation afforded a balance between parental preferences and preservation of anatomic options, allowing potential reconstruction of male or female phenotype as gender identity is ascertained thereby respecting both parent and patient rights. Parents valued a spectrum of options, transparency, and the team decision-making process., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Prior studies of outcomes following genitoplasty have reported high rates of surgical complications among children with atypical genitalia. Few studies have prospectively assessed outcomes after contemporary surgical approaches., Objective: The current study reported the occurrence of early postoperative complications and of cosmetic outcomes (as rated by surgeons and parents) at 12 months following contemporary genitoplasty procedures in children born with atypical genitalia., Study Design: This 11-site, prospective study included children aged ≤2 years, with Prader 3-5 or Quigley 3-6 external genitalia, with no prior genitoplasty and non-urogenital malformations at the time of enrollment. Genital appearance was rated on a 4-point Likert scale. Paired t-tests evaluated differences in cosmesis ratings., Results: Out of 27 children, 10 were 46,XY patients with the following diagnoses: gonadal dysgenesis, PAIS or testosterone biosynthetic defect, severe hypospadias and microphallus, who were reared male. Sixteen 46,XX congenital adrenal hyperplasia patients were reared female and one child with sex chromosome mosaicism was reared male. Eleven children had masculinizing genitoplasty for penoscrotal or perineal hypospadias (one-stage, three; two-stage, eight). Among one-stage surgeries, one child had meatal stenosis (minor) and one developed both urinary retention (minor) and urethrocutaneous fistula (major) (Summary Figure). Among two-stage surgeries, three children developed a major complication: penoscrotal fistula, glans dehiscence or urethral dehiscence. Among 16 children who had feminizing genitoplasty, vaginoplasty was performed in all, clitoroplasty in nine, external genitoplasty in 13, urethroplasty in four, perineoplasty in five, and total urogenital sinus mobilization in two. Two children had minor complications: one had a UTI, and one had both a mucosal skin tag and vaginal mucosal polyp. Two additional children developed a major complication: vaginal stenosis. Cosmesis scores revealed sustained improvements from 6 months post-genitoplasty, as previously reported, with all scores reported as good or satisfied., Discussion: In these preliminary data from a multi-site, observational study, parents and surgeons were equally satisfied with the cosmetic outcomes 12 months after genitoplasty. A small number of patients had major complications in both feminizing and masculinizing surgeries; two-stage hypospadias repair had the most major complications. Long-term follow-up of patients at post-puberty will provide a better assessment of outcomes in this population., Conclusion: In this cohort of children with moderate to severe atypical genitalia, preliminary data on both surgical and cosmetic outcomes were presented. Findings from this study, and from following these children in long-term studies, will help guide practitioners in their discussions with families about surgical management., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction: Pre-operative physical examination of male epispadias allows for classification of epispadias level as glanular (GE), penile (PE) or penopubic (PPE), and for delineation of anatomic anomalies. The incidence of associated extragenital abnormalities, such as vesicoureteral reflux (VUR), bladder neck (BN) abnormality and abnormal pubic diastasis (PD), and their impact on urinary continence has not yet been systematically studied., Objective: The goal of this study was to evaluate whether the more proximal level of epispadias correlated with associated extragenital anatomic anomalies seen on initial imaging or endoscopic evaluation, and whether these pre-operative findings contributed to subsequent surgical management and impacted on achieving urinary continence. It was hypothesized that the more severe forms of epispadias may be associated with a higher frequency of associated anomalies., Study Design: The study was an IRB-approved, retrospective case study of all male patients treated initially for isolated epispadias at the current institution between 1994 and 2011. Data collection was achieved by chart and radiology review evaluating PD, BN appearance, presence of VUR, surgical treatment, and urinary continence., Results: A total of 26 patients were identified and divided into three groups based on appearance at physical examination: four glanular (GE), eight penile (PE), and 14 penopubic (PPE); 17 patients had an abnormal BN. Reflux was noted in nine of 20 patients who had a voiding cystourethrogram (VCUG), two of which had an episode of pyelonephritis. Of the 22 patients past the age of toilet training, 17 were continent (64% (9/14) penopubic, 63% (5/8) penile, and 75% (3/4) glanular)., Discussion: Anatomic classification for male epispadias did not provide sufficient information regarding extragenital findings. This study provided new information regarding PD, BN appearance, presence of reflux, and ultimate urinary continence. Pubic diastasis and BN abnormalities were more frequently seen in more severe forms of epispadias, whereas VUR seemed more prevalent in less severe forms. A template for pre-operative evaluation was outlined. Limitations of the study were its retrospective design and relatively small cohort of patients, which reflected the rarity of the condition., Conclusion: Based on the information generated, additional anatomic information was generated regarding boys with epispadias. This information will help guide the evaluation and the management of these patients in the future., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background/aims: Parents of children born with disorders of sex development (DSD) often experience anxiety, but risk factors, including parental perception of the severity of their child's DSD, have not been examined. We hypothesized that severity of illness (SOI) ratings would relate to parental anxiety, and would be higher for parents of children with a potentially life-threatening DSD (e.g., 21-hydroxylase deficiency)., Methods: Eighty-nine parents (Mage = 33.0, 56.2% mothers) of 51 children (Mage in months = 8.7) with a DSD including ambiguous genitalia were recruited from 12 specialized DSD clinics. Parents completed questionnaires prior to genitoplasty, 6 months post-genitoplasty, and 12 months post-genitoplasty (if completed). Data were analyzed with linear mixed modeling., Results: Parental anxiety decreased over time, χ2(1) = 10.14, p < 0.01. A positive relationship between SOI and anxiety was found, with SOI being a strong predictor of anxiety (b = 0.53, p < 0.01; χ2[1] = 5.33, p < 0.05). An SOI by time interaction indicated SOI had an increasing effect on anxiety over time, b = 0.06, p < 0.05; χ2(1) = 6.30, p < 0.05. There was no diagnosis by SOI interaction., Conclusion: Parental anxiety decreased over time, but those with higher SOI ratings reported greater initial anxiety followed by slower resolution over time. Underlying etiology of DSD had no effect on the relationship between SOI and anxiety., (© 2018 S. Karger AG, Basel.)

Paediatric urological surgery is often required for managing congenital and acquired disorders of the genitourinary system. In this Series paper, we highlight advances in the surgical management of six paediatric urological disorders. The management of vesicoureteral reflux is evolving, with advocacy ranging from a less interventional assessment and antimicrobial prophylaxis to surgery including endoscopic injection of a bulking agent and minimally invasive ureteric reimplantation. Evidence supports early orchidopexy to improve fertility and reduce malignancy in boys with undescended testes. A variety of surgical techniques have been developed for hypospadias, with excellent outcomes for distal but not proximal hypospadias. Pelvi-ureteric junction obstruction is mostly detected prenatally; indications for surgery have been refined with evidence, and minimally invasive pyeloplasty is now standard. The outlook for patients with neurogenic bladder has been transformed by a combination of clean intermittent catheterisation, algorithms of diagnostic investigations, and innovative medical and surgical therapies. Posterior urethral valves are associated with considerable mortality; fetal diagnosis allows stratification of candidates for intervention, but ongoing bladder dysfunction in patients after valve ablation remains a cause of long-term morbidity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Bifid scrotum and hypospadias can be signs of undervirilization, yet boys presenting with these findings often do not undergo genetic evaluation. In some cases, identifying an underlying genetic diagnosis can help to optimize clinical care and improve guidance given to patients and families., Objectives: The aim of this study was to characterize current practice for genetic evaluation of patients with bifid scrotum, and to identify approaches with a good diagnostic yield., Methods: A retrospective study of the Boston Children's Hospital electronic medical records (1993-2015) was conducted using the search term "bifid scrotum" and clinical data were extracted. Data were abstracted into a REDCap database for analysis. Statistical analysis was performed using SPSS, SAS, and Excel software., Results: The search identified 110 subjects evaluated in the Urology and/or Endocrinology clinics for bifid scrotum. Genetic testing (including karyotype, microarray, or targeted testing) was performed on 64% of the subjects with bifid scrotum; of those tested, 23% (15% of the total cohort of 110 subjects) received a confirmed genetic diagnosis. Karyotype analysis, when performed, led to a diagnosis in 17% of patients. Of the ten instances when androgen receptor gene sequencing was performed, a pathogenic mutation was identified 20% of the time., Conclusion: This study demonstrated that the majority of individuals with moderate undervirilization resulting in bifid scrotum do not receive a genetic diagnosis. Over a third of the analyzed subjects did not have any genetic testing, even though karyotype analysis and androgen receptor (AR) sequencing were both relatively high yield for identifying a genetic etiology. Increased utilization of traditional genetic approaches could significantly improve the ability to find a genetic diagnosis., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Eosinophilic cystitis (EC) is an uncommon inflammatory disorder of uncertain etiology that has been described in adult and pediatric populations. We describe 3 recent cases of EC that presented as a mass lesion in pediatric patients from the New England region of the United States. All patients were initially suspected to have a malignancy, and biopsy was performed, which ultimately led to the diagnosis of EC. We propose the use of eosinophil density of >25 eosinophils per high-power field and myocyte degeneration as supportive histopathologic features to make this diagnosis. It is of utmost importance to consider EC in the differential diagnosis when approaching a pediatric patient with a bladder mass., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Disorders of sex development are challenging to evaluate and diagnose in the newborn. As pediatric urologists, our goals are to (1) identify patients who should be evaluated; (2) rule out life-threatening syndromes; and (3) involve a multidisciplinary team for evaluation, diagnosis, and gender assignment. This review briefly goes over the newborn differential diagnosis in disorders of sex development, highlights the important laboratory and imaging data needed, and discusses the multidisciplinary approach to gender assignment and care of these patients. Early involvement of the family in decision-making with the multidisciplinary team is paramount to a timely evaluation and diagnosis in these patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Little data exist about the surgical interventions taking place for children with disorders of sex development (DSD). Most studies that have evaluated cosmetic outcomes after genitoplasty have included retrospective ratings by a physician at a single center., Objective: The present study aimed to: 1) describe frequency of sex assignment, and types of surgery performed in a cohort of patients with moderate-to-severe genital ambiguity; and 2) prospectively determine cosmesis ratings by parents and surgeons before and after genital surgery., Study Design: This prospective, observational study included children aged <2 years of age, with no prior genitoplasty at the time of enrollment, moderate-to-severe genital atypia, and being treated at one of 11 children's hospitals in the United States of America (USA). Clinical information was collected, including type of surgery performed. Parents and the local pediatric urologist rated the cosmetic appearance of the child's genitalia prior to and 6 months after genitoplasty., Results: Of the 37 children meeting eligibility criteria, 20 (54%) had a 46,XX karyotype, 15 (40%) had a 46,XY karyotype, and two (5%) had sex chromosome mosaicism. The most common diagnosis overall was congenital adrenal hyperplasia (54%). Thirty-five children had surgery; 21 received feminizing genitoplasty, and 14 had masculinizing genitoplasty. Two families decided against surgery. At baseline, 22 mothers (63%), 14 fathers (48%), and 35 surgeons (100%) stated that they were dissatisfied or very dissatisfied with the appearance of the child's genitalia. Surgeons rated the appearance of the genitalia significantly worse than mothers (P < 0.001) and fathers (P ≤ 0.001) at baseline. At the 6-month postoperative visit, cosmesis ratings improved significantly for all groups (P < 0.001 for all groups). Thirty-two mothers (94%), 26 fathers (92%), and 31 surgeons (88%) reported either a good outcome, or they were satisfied (see Summary Figure); there were no significant between-group differences in ratings., Discussion: This multicenter, observational study showed surgical interventions being performed at DSD centers in the USA. While parent and surgeon ratings were discordant pre-operatively, they were generally concordant postoperatively. Satisfaction with postoperative cosmesis does not necessarily equate with satisfaction with the functional outcome later in life., Conclusion: In this cohort of children with genital atypia, the majority had surgery. Parents and surgeons all rated the appearance of the genitalia unfavorably before surgery, with surgeons giving worse ratings than parents. Cosmesis ratings improved significantly after surgery, with no between-group differences., (Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: A variant in steroidogenic factor-1 (SF-1, encoded by the gene NR5A1), p.Arg92Trp, has recently been reported in multiple families with 46,XX ovotesticular or testicular disorders of sex development (DSD). This amino acid change impacts the DNA-binding domain and perturbs gonadal differentiation pathways., Methods: Whole-exome sequencing was performed on a 46,XX subject with ovotesticular DSD., Results: Exome results identified a heterozygous NR5A1 variant, p.Arg92Gln, in the 46,XX ovotesticular DSD proband. This arginine-to-glutamine change has been previously reported in the homozygous state in a 46,XY patient with gonadal and adrenal dysgenesis, though 46,XY and 46,XX heterozygous carriers of this variant have not been previously reported to have any clinical phenotype., Conclusions: The NR5A1 p.Arg92Gln variant, which has thus far only been seen in a family with 46,XY DSD, most likely contributes to the ovotesticular DSD in this case. In light of the recent reports of unrelated 46,XX subjects with testicular or ovotesticular DSD with the NR5A1 variant p.Arg92Trp, it appears that other mutations in the DNA binding domain have the potential to impact the factors determining testicular and ovarian differentiation. This case demonstrates the variability of phenotypes with the same genotype and broadens our understanding of the role of SF-1 in gonadal differentiation., (© 2016 S. Karger AG, Basel.)

Background: Undervirilized 46,XY males with bifid scrotum often pose a diagnostic challenge, and the majority of cases typically do not receive a genetic diagnosis. NR5A1 mutations can be seen in 10-20% of the cases and are a relatively common cause of undervirilization., Methods: Whole-exome sequencing was utilized to study 10 undervirilized 46,XY subjects with bifid scrotum., Results: Exome sequencing identified novel NR5A1 variants, both affecting exon 7, in 2 of the 10 subjects with bifid scrotum. Subject 1 had a heterozygous frameshift variant, c.1150delC, p.Leu384fsTer1, within the ligand-binding domain inherited from his unaffected father. Subject 2 had a novel splice-site variant c.1139-2T>C, affecting the canonical splice acceptor site for exon 7 and also disrupting the ligand-binding domain. Both subjects had serum testosterone levels within the normal range as infants., Conclusions: We describe two novel NR5A1 variants, demonstrating mutations in this gene as a common cause of milder cases of 46,XY undervirilization. Whole-exome sequencing results yielded the diagnosis in 2 out of 10 cases without a previous diagnosis, supporting the value of this approach. Significant genotype-phenotype variability was also noted with Subject 1's paternal inheritance from his unaffected father., (© 2016 S. Karger AG, Basel.)

Purpose: We describe our experience with 2-stage proximal hypospadias repair. We report outcomes, and patient and procedure characteristics associated with surgical complications., Materials and Methods: We retrospectively studied patients with proximal hypospadias who underwent staged repair between January 1993 and December 2012. Demographics, preoperative management and operative technique were reviewed. Complications included glans dehiscence, fistula, meatal stenosis, nonmeatal stricture, urethrocele/diverticula and residual chordee. Cox proportional hazards model was used to evaluate the associations between time to surgery for complications and patient and procedure level factors., Results: A total of 134 patients were included. Median patient age was 8.8 months at first stage surgery and 17.1 months at second stage surgery, and median time between surgeries was 8 months. Median followup was 3.8 years. Complications were seen in 71 patients (53%), with the most common being fistula (39 patients, 29.1%). Reoperation was performed in 66 patients (49%). Median time from urethroplasty to surgery for complication was 14.9 months. Use of preoperative testosterone decreased risk of undergoing surgery for complication by 27% (HR 0.73, 95% CI 0.55-0.98, p = 0.04). In addition, patients identified as Hispanic were at increased risk for undergoing surgery for complications (HR 2.40, 95% CI 1.28-4.53, p = 0.01)., Conclusions: We review the largest cohort of patients undergoing 2-stage hypospadias repair at a single institution. Complications and reoperation rates were approximately 50% in the setting of complex genital reconstruction., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Orchidometric evaluation of the testis has been proposed as a cost-effective alternative to measurement of the testis with high-frequency linear ultrasound, which may be costly in terms of hospital resources and patient time. It is known from animal experiments, autopsy series, and small clinical studies that, under ideal conditions, orchidometry may approximate ultrasound measurement. However, little is known of the effectiveness of orchidometry in the clinical setting in a large sample of adolescents with varicocele., Objective: We sought to analyze the performance characteristics of Rochester orchidometry and its agreement with ultrasound testis volumes in boys with varicocele., Study Design: Our institutional varicocele database was analyzed from March 2000 to May 2013, including all boys with Rochester orchidometric measurement and ultrasound-based volume measurement performed on the same day. The Lambert formula (L*W*H*0.71) was used to calculate ultrasound volumes. Seven-hundred and twenty measurements were included: 360 of the left testis, and 360 of the right testis. Each subject was included once; in the event of serial measurements the earliest measurement was analyzed. Bland-Altman plots with 95% limits of agreement were used to compare orchidometry and ultrasound measurements. Analysis was performed with JMP, v11 Pro., Results: Age at exam ranged from 11.2 to 18.5 years (median 15.8). With respect to varicocele grade, 183 (50.8%) were grade III, 113 (31.4%) were grade II, 42 (11.7%) were grade I, 12 (0.3%) were bilateral, and 10 (0.3%) were ungraded. Mean ultrasound left testis volume was 13.6 cc (SD 6.6) and mean right testis volume was 15.1 cc (SD 6.9). Eleven surgeons performed the orchidometric measurements; one surgeon performed 71% of the exams. Mean overestimation on the right was 2.0 cc (SD 4.2) and on the left was 1.9 cc (SD 4.1); each was highly statistically significant (p < 0.0001, paired t test). Error was correlated with testis size, implying a greater degree of overestimation with increasing volume (p < 0.01, Pearson's correlation 0.09). Amount of volume overestimation and variability was not significantly different for right and left testis. Sensitivity and specificity of Rochester orchidometry to detect a testis volume differential (TVD) of 20% were 33% (95% CI 23-42%) and 96% (95% CI 92-97%), respectively. Testis size, varicocele grade, or examining surgeon had no effect on sensitivity or specificity., Discussion: We have shown in a large series of boys with adolescent varicocele that in clinical practice there is a modest degree of overestimation of testis volume on average (1.9-2.0 cc), although there is a large range of volume estimation, such that the 95% confidence interval ranges are quite wide, from approximately 6 cc lower than the true volume to 10 cc greater than the true volume. Furthermore, the low sensitivity (33%) of orchidometry for 20% testis volume differential renders this a suboptimal screening tool for this clinical parameter, which has been shown to be associated with semen analysis outcomes. Knowledge of the performance characteristics of orchidometry is similarly important for research, as factors such as the prevalence of testis volume differential are then dependent on the modality of measurement. Lastly, that this was conducted over a long time course with several surgeons involved suggests that these data reflect real-world application of orchidometry., Conclusions: Appropriate caution should be exercised when relying solely on orchidometric evaluation of the testis. Rochester orchidometry in general appears to overestimate testis size, and there is wide variability in the estimation. In clinical practice, the sensitivity of Rochester orchidometry is modest in detecting a 20% testis volume differential; this difference would be missed in approximately two out of three of boys screened with orchidometry alone., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: We evaluated the relationship between testicular volume differential, total testis volume and total motile sperm count in adolescents with varicocele. Prior reports have been inconclusive regarding the association of testis volume with semen analysis parameters., Materials and Methods: We retrospectively reviewed a single institution database of Tanner 5 adolescents with nonoperated left varicocele with at least 1 semen analysis available. Patients were included in analysis if they had clinical left varicocele, ultrasound measurement of testis volume and no prior inguinal or scrotal surgery., Results: We analyzed the records of 100 patients. Mean ± SD age at presentation was 15.2 ± 3.5 years. The mean testicular volume differential was 8% ± 23% and 31 patients (31%) had a greater than 20% testicular volume differential. Mean total testis volume was 30.4 ± 13.3 cc. Varicocele was grade 3 in 39 patients, grade 2 in 50, grade 1 in 8 and ungraded in 3. Median total motile sperm count in the cohort was 42.0 (IQR 9.2, 105.8). ROC analysis with the Youden index indicated an optimal total testis volume cutoff of 30 cc to predict the total motile sperm count. In a multivariable logistic model accounting for age and varicocele grade a testicular volume differential of greater than 20% was associated with twice the odds of a total motile sperm count of less than 20 million per cc (OR 2.1, 95% CI 1.02-4.12, p = 0.04). Total testis volume less than 30 cc more than quadrupled the odds of a total motile sperm count of less than 20 million per cc (OR 4.2, 95% CI 1.8-9.7, p <0.001)., Conclusions: Total testis volume and the testicular volume differential are associated with semen analysis outcomes in adolescents with varicocele. A testicular volume differential of greater than 20% doubles the odds of a low total motile sperm count. A total testis volume of less than 30 cc quadruples the odds of a low total motile sperm count., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Varicoceles in prepubertal boys are uncommon and little is known of the natural history. Historically, a large percentage of these boys have undergone surgical repair with the belief that such early presentation carried a worse prognosis, making assessment of longitudinal outcomes difficult., Objective: While there may be concern that varicocele could represent a progressive disease and therefore prepubertal presentation would portend a worse prognosis, we hypothesized that there would be no difference between the prepubertal boys and other adolescents with varicocele., Study Design: We retrospectively reviewed a database of boys at a single institution with a documented left-sided varicocele between 1995 and 2011. Inclusion criteria were one or more of the following: 1. Clinician-documented Tanner 1 status, 2. Right testis orchidometric or ultrasound calculated volume of ≤3 cc's. Patients were drawn from a prospectively maintained database of all boys presenting to the outpatient urology clinic receiving a diagnosis of varicocele. A cohort of adolescent boys was assembled by matching as closely as possible with respect to testis volume disparity and grade of varicocele. All matches were within 2% of volume difference. Volume was calculated using the length*width*height*0.71 formula. Testis size disparity was set to a threshold of ≥20% using the Lambert formula: (VolumeRight - VolumeLeft)/VolumeRight*100%. Our primary outcome was defined as hypotrophy or the need for surgery for hypotrophy at the termination of the study. We planned a single subgroup analysis of boys based on presentation with or without hypotrophy. The decision for surgery or observation was made by the individual clinician at the time of patient assessment., Results: On presentation, the prepubertal cohort was younger (10.8 vs 14.1 years), and with smaller left (2.4 vs 11.6 cc) and right (2.4 vs 11.6 cc) testis volume. There were no significant differences with respect to varicocele grade and volume differentials at presentation. At the end of the study, 76% of the prepubertal cohort had neither hypotrophy nor the requirement for operation, compared with 83% of the matched cohort (P = 0.71, Fisher's exact test). Similarly, there were no significant differences in outcome when comparing prepubertal boys with initial symmetry or hypotrophy to their matched cohort of older adolescents., Discussion: The prepubertal varicocele is a rare clinical problem for which little data exists to guide the clinician. In a review of Pubmed indexed English language manuscripts, we were only able to find five papers with information on Tanner stage; only 31 prepubertal boys have longitudinal data reported. This study approximately doubles the number of boys for whom such data is available in the literature. Our chief limitation was sample size. A power analysis indicated that a final-analysis cohort of 90 prepubertal boys would be required to detect a 20% difference in outcome between that group and a matched cohort of pubertal or post-pubertal boys. We propose that given the lack of evidence for worse outcomes in prepubertal boys with varicocele that prepubertal status, in and of itself, not be considered an additional indication for correction of varicocele., Conclusion: In our retrospective cohort of prepubertal boys with left testis varicocele and their matched cohort, we did not detect a difference in the rate of good outcomes, defined as the absence of hypotrophy and lack of need for surgical intervention. While we may have suspected, as have others, that prepubertal presentation would have conveyed a more pressing need to intervene, it is likely that these boys represent the very same patients that we see more commonly later in their adolescence, and should thus be managed in a similarly conservative fashion., (Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)