A scoping review on chordee correction in boys with ventral congenital penile curvature and hypospadias.

Introduction: Congenital penile curvature (PC), often concomitant with hypospadias, poses challenges in urology. Surgical correction techniques, including plication and corporotomy, lack standardized guidelines. This study aims to address the paucity of high-level evidence by comprehensively reviewing the outcomes of PC correction procedures in patients with and without hypospadias. This will inform clinical decision-making and provide insights for future research and meta-analyses. Methods: We conducted this scoping review in accordance with the JBI Manual for Evidence Synthesis and PRISMA-ScR guidelines. An extensive literature search was performed and comparative studies published in English up to June 2023 were included. The studies were divided into three categories: PC without hypospadias, PC with hypospadias, and studies comparing two or more materials for covering the ventral corporotomy. Data extraction comprised author details, patient characteristics, study design, interventions, outcomes, and complications. Methodological quality was assessed using the Newcastle-Ottawa Scale. Results: Forty-two studies were included in the review, which collectively comprised 3180 patients. Thirteen comparative studies reported the outcomes of surgery for congenital PC without hypospadias, 22 studies compared different techniques of PC correction in patients with hypospadias and 7 studies compared the type of materials for coverage following ventral corporotomy. In cases of PC without hypospadias, the most commonly reported surgery was the Nesbit's plication. For PC with hypospadias correction, the results of ventral corporotomy were superior to that of dorsal plication in most of the studies. The two-stage repair had better results when compared to the one-stage repair for patients with perineo-scrotal hypospadias. In studies comparing materials for coverage of ventral corporotomy, the tunica vaginalis flap or graft was utilized most commonly. The majority of the studies reported a success rate ranging from 85% to 100%. The methodological quality was high in all but four studies. Conclusion: Plication procedures are generally preferred for PC without hypospadias, but they result in penile shortening. For those with hypospadias, corporotomy is associated with superior outcomes than plication, especially for those with severe curvature and redo procedures. For ventral corporotomy coverage, the tunica vaginalis flap or graft is the most commonly reported tissue in the literature.

Spontaneous urinary bladder regeneration after subtotal cystectomy increases YAP/WWTR1 signaling and downstream BDNF expression: Implications for smooth muscle injury responses.

Rodents have the capacity for spontaneous bladder regeneration and bladder smooth muscle cell (BSMC) migration following a subtotal cystectomy (STC). YAP/WWTR1 and BDNF (Brain-derived neurotrophic factor) play crucial roles in development and regeneration. During partial bladder outlet obstruction (PBO), excessive YAP/WWTR1 signaling and BDNF expression increases BSMC hypertrophy and dysfunction. YAP/WWTR1 and expression of BDNF and CYR61 were examined in models of regeneration and wound repair. Live cell microscopy was utilized in an ex vivo model of STC to visualize cell movement and division. In Sprague-Dawley female rats, STC was performed by resection of the bladder dome sparing the trigone, followed by closure of the bladder. Smooth muscle migration and downstream effects on signaling and expression were also examined after scratch wound of BSMC with inhibitors of YAP and BDNF signaling. Sham, PBO and incision (cystotomy) were comparators for the STC model. Scratch wound in vitro increased SMC migration and expression of BDNF, CTGF and CYR61 in a YAP/WWTR1-dependent manner. Inhibition of YAP/WWTR1 and BDNF signaling reduced scratch-induced migration. BDNF and CYR61 expression was elevated during STC and PBO. STC induces discrete genes associated with endogenous de novo cell regeneration downstream of YAP/WWTR1 activation.

Neural network non-linear modeling to predict hypospadias genotype-phenotype correlation.

INTRODUCTION: Hypospadias is an abnormal development of the urethral, ventral skin and corporeal bodies. Urethral meatus and ventral curvature have been historically the landmarks to define clinical severity. Genotyping has never been explored as a clinical predictor. Available reports have demonstrated a correlation between genetic mutations and syndromic hypospadias with poor surgical outcomes. We hypothesize that inclusion of genotyping can serve at classifying all types of hypospadias. We present the use of neural network algorithm to evaluate phenotype/genotype correlations and propose its potential clinical applicability. METHODS: A systematic review was performed from January 1974 to June 2022. Literature was retrieved from Medline, Embase, Web of Science and Google Scholar. Included manuscripts were those that had an explicit anatomical description of hypospadias phenotype (urethral meatus location following an anatomical description) and a defined genotype (genetic mutation) description. Cases with more than one variant/mutation were excluded. A comprehensive phenotype-genotype statistical analysis using neural network non-linear data modeling SPSS™ was performed. RESULTS: Genotype-Phenotype analysis was performed on 1731 subjects. Of those, 959 (55%) were distal and 772 (45%) proximal. 49 genes with mutations were identified. Neural network clustering predicted better for coronal (90%) and glanular (80%), and lowest for midshaft (22%) and perineal (45%). Using genes as predictor factor only, the model was able to highly and more accurately predict the phenotype for coronal and glanular hypospadias. The following genotypes showed association to a specific phenotype: AR gene n.2058G > A for glanular (p<0.0001), n.480C  >  T for coronal (p = 0.034), R840C for perineal (p = 0.002), MAMLD1 gene c.2960C > T for coronal (p< 0.0001), p. G289S for glanular (p<0.0001), gene SRD5A2 607G > A for scrotal (p<0.0001), c16C > T for penoscrotal (p<0.0001), c59 T  >  c for perineal (p = 0.042), V89L for midshaft and scrotal (p<0.0001, p = 0.041; respectively). DISCUSSION: Hypospadias phenotype has always been described from a purely anatomical perspective. Our results demonstrate that current phenotyping has poor correlation to the genotype. Higher genotype/phenotype correlation for distal hypospadias proves the clinical applicability of genotyping these cases. The concept and classification of differences in sexual development needs to be reconsidered given high positive yield reported for distal hypospadias. Given the better predictive value of genotyping in correlation to the phenotype, future efforts should be directed towards using the genotype. CONCLUSION: Hypospadias has poor phenotype/genotype correlation. Sequencing all hypospadias phenotypes may add clinical value if used in association to other predictive variables. Neural network analysis may have the ability to combine all these variables for clinical prediction.

Perinatal testicular torsion: The clear cut, the controversial, and the "quiet" scenarios.

BACKGROUND: Perinatal testicular torsion (PTT) is a catastrophic event that occurs in utero or up to 30 days postnatally, with testicular loss being the most common outcome. OBJECTIVE: To assess clinical evaluation, surgical management and clinical outcomes in patients with PTT in a quaternary referral pediatric center, to determine testicular salvageability and propose future management options. METHODS: We retrospectively reviewed a cohort of males born outside the quaternary center with a diagnosis of PTT, from May 2000 to July 2020. Data collection included mode of delivery, gestational age, birth weight, testicular examination at birth, clinical presentation, ultrasound results at diagnosis, surgical management and findings, perioperative complications, and follow-up. RESULTS: 62 patients, including 2 patients with bilateral asynchronous PTT, were identified. Median (IQR) gestational age and birth weight were 39 (38-39.4) weeks and 3.4 (3.1-3.72) kg, respectively. Abnormal testicular examination at birth was found in 69% (Table 1). Doppler ultrasound was performed in all but 1 patient. 59 patients underwent surgery, 21 within 4 h, with bilateral exploration in 44 cases. Affected and non-affected testicles were explored in 76% and 98% of cases, respectively. 3 "nubbins" were found, of which 2 were excised. 3 nonsurgical complications were identified. During a median (IQR) follow-up of 3 (3-3) months, 63 testicles were removed or found to be non-functional, with compensatory hypertrophy in 38% of patients. CONCLUSION: Given that 3% of our patients presented with asynchronous bilateral PTT, as well as the safety of general anesthesia in a referral pediatric hospital, early bilateral scrotal exploration of PTT is recommended. LEVEL OF EVIDENCE: IV.

Genetics: The diagnostic frontier in pediatric urology.

In the course of human history few scientific breakthroughs can rival the importance of the discovery of DNA. Our ever increasing ability to unravel the secrets contained in this molecule allow new insight in to the etiology and eventual treatment of human conditions ranging from congenital structural disorders to cancer. It is the focus of this article to touch upon sequencing technologies and their potential to provide information that can revolutionize healthcare.

Prolonged warm ischemia time leads to severe renal dysfunction of donation-after-cardiac death kidney grafts.

Kidney transplantation with grafts procured after donation-after-cardiac death (DCD) has led to an increase in incidence of delayed graft function (DGF). It is thought that the warm ischemic (WI) insult encountered during DCD procurement is the cause of this finding, although few studies have been designed to definitely demonstrate this causation in a transplantation setting. Here, we use a large animal renal transplantation model to study the effects of prolonged WI during procurement on post-transplantation renal function. Kidneys from 30 kg-Yorkshire pigs were procured following increasing WI times of 0 min (Heart-Beating Donor), 30 min, 60 min, 90 min, and 120 min (n = 3-6 per group) to mimic DCD. Following 8 h of static cold storage and autotransplantation, animals were followed for 7-days. Significant renal dysfunction (SRD), resembling clinical DGF, was defined as the development of oliguria < 500 mL in 24 h from POD3-4 along with POD4 serum potassium > 6.0 mmol/L. Increasing WI times resulted in incremental elevation of post-operative serum creatinine that peaked later. DCD120min grafts had the highest and latest elevation of serum creatinine compared to all groups (POD5: 19.0 ± 1.1 mg/dL, p < 0.05). All surviving animals in this group had POD4 24 h urine output < 500 cc (mean 235 ± 172 mL) and elevated serum potassium (7.2 ± 1.1 mmol/L). Only animals in the DCD120min group fulfilled our criteria of SRD (p = 0.003), and their renal function improved by POD7 with 24 h urine output > 500 mL and POD7 serum potassium < 6.0 mmol/L distinguishing this state from primary non-function. In a transplantation survival model, this work demonstrates that prolonging WI time similar to that which occurs in DCD conditions contributes to the development of SRD that resembles clinical DGF.

Time Driven Activity Based Costing of Management Pathways for Vesicoureteral Reflux.

INTRODUCTION: The approach to the management of vesicoureteral reflux remains variable despite being a common pediatric diagnosis, which makes costing unpredictable. The aim of our study is to employ time driven activity based costing to characterize institutional costs of 3 management pathways for vesicoureteral reflux. METHODS: We developed process maps for vesicoureteral reflux management based on practice guidelines applicable to a hypothetical female patient with vesicoureteral reflux index with grade 3 unilateral reflux without bowel bladder dysfunction at our institution. The costs of 3 management pathways were described, including watch and wait, minimally invasive endoscopic surgery with dextranomer/hyaluronic acid and open re-implantation surgery. Costs for each pathway were calculated using the capacity cost rate ($/minute) for institutional resources and time estimates of resource use captured through direct observation and electronic medical record data. Clinical outcomes such as the breakthrough urinary tract infections or renal scarring were not addressed in this cost description. RESULTS: A substantial range of total costs ($CAD) was observed for all pathways including watch and wait ($1,683.58 to $2,041.12), minimally invasive endoscopic surgery ($2,616.35 to $4,012.89) and open re-implantation surgery ($3,317.76 to $3,924.82). Total costs for a single dimercaptosuccinic acid scan accounted for 8% to 15% of any pathway's overall costs. Material costs for voiding cystourethrogram imaging and endoscopic surgery were high at 59% and 64% to 76% of their individual total costs, respectively. For open re-implantation surgery, high costs were attributable to the longer use of operating room space and inpatient postoperative stay. CONCLUSIONS: Time driven activity based costing demonstrates significant cost variability in vesicoureteral reflux treatment modalities and identified local cost drivers to target. Results from this study may be used to inform future cost-effectiveness analyses.

Clinically and biologically relevant subgroups of Wilms tumour defined by genomic and epigenomic analyses.

BACKGROUND: Although cure rates for Wilms tumours (WT) are high, many patients receive therapy with attendant long-term complications. Our goal was to stratify WT using genome-wide analyses to identify candidate molecular features for patients who would benefit from a reduction in therapy. METHODS: We generated DNA methylation and exome sequencing data on WT-kidney pairs (n = 57) and unpaired tumours (n = 27) collected either at our centre or by the Children's Oncology Group. Samples were divided into a discovery set (n = 32) and validation set (n = 52). RESULTS: Analysis of DNA methylation revealed two subgroups of WT with distinct features. Subgroup A has a similar DNA methylation profile to mature kidney, while Subgroup B has genome-wide dysregulation of DNA methylation. The rate of non-synonymous missense mutations and segmental chromosomal aberrations was higher in Subgroup B tumours, suggesting that this group has genome instability related to its epigenetic state. Subgroup A had a higher proportion of cases of bilateral disease. Tumours with high-risk histology or from patients who relapsed were only found in Subgroup B. CONCLUSION: We have identified subgroup-specific molecular events that could inform future work supporting more targeted therapeutic approaches and patient stratification. We propose a novel developmental tumour model based on these findings.

Do post-operative phone calls enhance family satisfaction and outcomes after outpatient pediatric urological surgeries? A prospective study.

INTRODUCTION: This study assesses whether post-operative check-in phone calls (POPC) performed within 48 h of outpatient pediatric urological surgeries by a non-medical professional (NMP) would increase patient/family satisfaction and minimize extraneous resource use by increasing email/telephone communication, while reducing emergency department (ED) visits within 30 days of that procedure. METHODS: Families of patients undergoing ambulatory pediatric urology surgeries were enrolled over 8 weeks. Group 1 did not receive POPC. Group 2 received a POPC within 48 h of their operation by a NMP. Both groups received a phone-call survey 2 weeks after surgery to assess families' perioperative satisfaction. RESULTS: In total, 74 families were enrolled (Group 1 = 44, Group 2 = 31). The response rates to phone surveys for Groups 1 and 2 were 59.1% and 77.4%, respectively. POPC did not improve perioperative satisfaction, nor did it significantly promote the use of nursing email/telephone communication (19.2% vs. 4.2%, p = 0.128) or reduce ED visits (15.4% vs. 0.0%, p = 0.111). However, all families in Group 2 thought POPC was timed appropriately and 79.1% perceived it to be helpful in reducing post-operative anxiety. CONCLUSION: POPC by a NMP within 48 h of surgery may not affect perioperative satisfaction of families of patients undergoing same-day pediatric urology surgery but may have an impact in reducing post-operative anxiety.

Turning a new "page": ways to decrease the number of pages after hours without compromising patient care

Background: Pages to house staff after hours, especially overnight, lead to interrupted sleep and fatigue the next day. Although some pages are urgent, others may not need an immediate response. In this study we aimed to identify unwarranted pages and to establish ways to reduce them. Methods: Over 2 months, all pages to the Department of Pediatric Urology at the Hospital for Sick Children in Toronto, Canada, during call hours were documented, including the assessment of the responding physicians of their medical necessity. After analyzing the reasons for inappropriate pages, we took several steps to try to reduce them without impairing patient care. One year later, pages were tracked again to evaluate the efficacy of our interventions. Results: In the initial measurement period, no calls from parents and approximately 50% of the in-hospital pages (15 of 36 pages from the wards, 27 of 49 pages from the emergency department, 17 of 31 pages requesting consultations, and 8 of 8 pages from the inhouse pharmacy and outside pharmacies) were considered medically urgent. The reasons for unwarranted pages were inconsistent parent teaching, lack of adequate triaging and prioritizing on the ward and lack of awareness of the structure of the on-call provisions among different services in the hospital. Several steps were taken to streamline the teaching of parents and nurses, standardize information, provide alternative means of communication within the hospital and restrict parents' access by phone to the urologist on call. One year later, the number of pages had decreased by 70%. Conclusion: Although physician coverage throughout the day and night is necessary for high-quality and safe patient care, communication with on-call physicians should be only for appropriate reasons. The provision of consistent teaching and alternative communication channels can improve patient care as well as decrease the number of after-hour pages.

Contexte: Les appels au personnel interne par téléavertisseur, surtout la nuit, perturbent le sommeil et entraînent de la fatigue le lendemain. Même si certains de ces appels sont urgents, d'autres ne nécessitent pas de réponse immédiate. Avec cette étude nous avons voulu identifier les appels par téléavertisseur qui sont injustifiés et trouver des façons d'en réduire le nombre. Méthodes: Sur une période 2 mois, nous avons documenté tous les appels par téléavertisseur adressés durant les heures de garde au service d'urologie pédiatrique de l'Hôpital SickKids de Toronto, au Canada, et demandé aux médecins y ayant répondu d'en évaluer le bien-fondé au plan médical. Après avoir analysé les raisons des appels jugés injustifiés, nous avons adopté plusieurs mesures pour en réduire le nombre sans compromettre les soins. Un an plus tard, nous avons de nouveau comptabilisé les appels par téléavertisseur pour mesurer l'efficacité de nos interventions. Résultats: Durant la période de mesure initiale, aucun appel des parents n'a été considéré médicalement urgent, tout comme environ 50 % des appels provenant de l'hôpital même (15 appels sur 36 des unités de soins, 27 appels sur 49 du service des urgences, 17 appels sur 31 pour des demandes de consultation et 8 appels sur 8 de la pharmacie de l'hôpital ou de pharmacies de l'extérieur). Les raisons des appels injustifiés étaient entre autres incohérence dans l'enseignement aux parents, triage et priorisation inadéquats à l'unité de soin et méconnaissance des différents services de l'hôpital quant à la structure et au fonctionnement du système de garde. Plusieurs mesures ont été prises pour simplifier l'enseignement aux parents et au personnel infirmier, standardiser l'information, fournir d'autres moyens de communication dans l'hôpital même et restreindre l'accès des parents à l'urologue de garde par téléphone. Un an plus tard, le nombre d'appels avait diminué de 70 %. Conclusion: Même si les médecins doivent être joignables jour et nuit pour assurer la qualité des soins et la sécurité des patients, les raisons de communiquer avec eux doivent être appropriées. Le rappel des consignes et le recours à d'autres canaux de communication peuvent améliorer les soins aux patients et réduire le nombre d'appels le soir et la nuit.

Artificial Intelligence. How Artificial is Urology Practice Becoming? / Inteligencia artificial. ¿Qué tan artificial se está volviendo la práctica urológica?

The evolution of medical practice has changed from the most basic tool of patient interrogation to current technologies of artificial intelligence and machine-learning driven practice.[1] Traditionally at the forefront of technology, once again urology has an opportunity to embrace and lead in these rapid changes in medical practice.

Variability among Canadian pediatric surgeons and pediatric urologists in the management of cryptorchidism in boys before the publication of major guidelines: a retrospective review of a single tertiary centre

Background: Before 2014, there was a lack of recommendations on managing cryptorchidism, or undescended testis (UDT), from a large pediatric urological or surgical organization. We assessed the variability in management of UDT among pediatric urologists and pediatric surgeons at a single tertiary pediatric referral centre before publication of major guidelines. Methods: We performed a retrospective review of the electronic records of patients who underwent primary unilateral or bilateral orchidopexy at our centre between January 2012 and January 2014. Results: A total of 488 patients (616 testes) were identified, of whom 405 (83.0%) and 83 (17.0%) were managed by pediatric urologists and pediatric surgeons, respectively. There was no difference in baseline characteristics, including age seen in clinic or at surgery, testis location/palpability and availability of preoperative ultrasonograms, of patients seen by the 2 groups. Pediatric surgeons ordered preoperative ultrasonography more often than pediatric urologists (25.3% v. 3.7%, p < 0.001). With palpable UDTs, although both groups used open approaches, pediatric urologists preferred a scrotal approach (56.9%), and pediatric surgeons approached most testes inguinally (98.8%). With nonpalpable UDTs, laparoscopic approaches were preferred by both groups; however, pediatric urologists used a 2-stage Fowler­Stephens approach more often than pediatric surgeons (48.4% v. 15.8%, p < 0.001). Conclusion: There was wide variation in the management of primary UDT between pediatric urologists and pediatric surgeons before the publication of guidelines. The most prominent difference between the 2 groups was in the ordering of preoperative ultrasonography. Future assessment of change in practice patterns may elucidate whether guidelines are an effective tool for standardization of practice.

Contexte: Avant 2014, on ne disposait pas de recommandations émanant d'une grande organisation urologique ou chirurgicale pédiatrique pour la prise en charge de la cryptorchidie (absence d'un ou des deux testicules dans le scrotum). Nous avons évalué les divers types de prise en charge de la cryptorchidie chez les urologues et les chirurgiens pédiatriques dans un seul centre tertiaire de référence pédiatrique avant la publication de lignes directrices majeures. Méthodes: Nous avons procédé à une revue rétrospective des dossiers électroniques de patients ayant subi une orchidopexie unilatérale ou bilatérale primaire dans notre centre entre janvier 2012 et janvier 2014. Résultats: En tout, 488 patients (616 testicules) ont été identifiés, dont 405 (83,0 %) et 83 (17,0 %) ont été traités respectivement par des urologues et des chirurgiens pédiatriques. On n'a noté aucune différence quant aux caractéristiques de départ des patients vus par les 2 groupes, telles que l'âge lors de la consultation à la clinique ou lors de la chirurgie, la localisation/palpabilité des testicules et le recours à l'échographie préopératoire. Les chirurgiens pédiatriques ont demandé une échographie préopératoire plus souvent que les urologues pédiatriques (25,3 % c. 3,7 %, p < 0,001). En présence de cryptorchidie palpable, même si les 2 groupes ont utilisé une approche ouverte, les urologues pédiatriques ont préféré l'approche scrotale (55,4 %) et les chirurgiens pédiatriques l'approche inguinale (98,8 %). En présence de cryptorchidie non palpable, les approches laparoscopiques ont été privilégiées par les 2 groupes; toutefois, les urologues pédiatriques ont utilisé une approche Fowler­Stephens en 2 temps plus souvent que les chirurgiens pédiatriques (48,4 % c. 15,8 %, p < 0,001). Conclusion: On a noté une grande variation dans la prise en charge de la cryptorchidie primaire entre les urologues et les chirurgiens pédiatriques avant la publication des lignes directrices. La principale différence entre les 2 groupes concernait le recours à l'échographie préopératoire. L'évaluation future des changements affectant la pratique permettrait de déterminer si les lignes directrices sont un outil efficace pour sa standardisation.

A mixed methods study of challenges in the implementation and use of the surgical safety checklist.

BACKGROUND: The surgical safety checklist is an evidence-based global initiative designed to reduce perioperative morbidity and mortality. However, the expounded benefits of the surgical safety checklist have not been realized in naturalistic settings. This may be related to the quality of surgical safety checklists being performed in operating rooms. METHODS: In this explanatory, sequential, mixed-methods study, 2 trained observers used a standardized tool to record the compliance and quality of the surgical safety checklist completed during 51 surgeries performed at a pediatric academic hospital. We compared compliance with each phase of the surgical safety checklist, the number of checklist items completed, and professionals initiating the surgical safety checklist across surgical specialties and case urgency levels. Interviews with nurses, anesthesiologists, and surgeons (n = 18) were subsequently conducted to explore and contextualize the findings. RESULTS: Hospital-recorded surgical safety checklist compliance (94%, 100%, and 100% on briefing, time out, and debriefing) was higher than the proportion of checklist items completed in matched cases (26%, 59%, and 42%, respectively). Thematic analysis of the interview data suggests this may result from limited staff "buy in," arising from the "top-down" mandated nature of the surgical safety checklist, the perceived lack of benefit in surgical safety checklist completion, and redundancies with other operating room processes. This has led to the surgical safety checklist becoming "an exercise in box ticking" (ie, compliance is recorded without ensuring quality), thereby obfuscating potential safety benefits. CONCLUSION: These results highlight that compliance data are insufficient for monitoring surgical safety checklist quality. Our study suggests that surgical safety checklist quality may be enhanced through better calibration of the surgical safety checklist with existing procedures and staff expectations through a bottom-up implementation strategy.

A Canadian national survey: understanding the differences in management of cryptorchidism among pediatric surgeons and pediatric urologists.

BACKGROUND: This investigation aims to assess the variability in practice patterns regarding management of children with cryptorchidism (UDT) among pediatric urologists (U) and pediatric surgeons (S) practicing in Canada. METHODS: All active members of Pediatric Urologists of Canada (PUC) and Canadian Association of Pediatric Surgery (CAPS) were invited to participate in an online multiple-choice type questionnaire with clinical scenarios in management of UDT. Responses were compared between U and S using Fisher's exact test. RESULTS: The response rates were 74% and 79% among CAPS members (54/73) and PUC members (27/34) respectively. CAPS members were more likely to order diagnostic ultrasounds prior to surgery (44.4% vs 18.5%, p = 0.027). For palpable testis, most (80%) CAPS members favored the classic inguinal approach, while most PUC members did not demonstrate a clear preference, and were flexible with their approach depending on the position of the palpated testes (55%; p < 0.001). There was no statistically significant difference in preferred approach to unilateral or bilateral nonpalpable testis. However, for both palpable and nonpalpable bilateral UDT, more CAPS members preferred metachronous correction, compared to PUC members who opted to approach them synchronously (p = 0.008, 0.002, respectively). CONCLUSION: Preferences with regard to use of diagnostic tools such as US, surgical approach for palpable testes and bilateral UDTs were not consistent between the two surgical specialties who perform orchidopexy across Canada. Both groups were compliant with guideline recommendations, with the exception of utilizing preoperative ultrasounds, which is uniformly not recommended by the most recent guidelines. LEVEL OF EVIDENCE: This is a level II evidence study.

DNA Methylation Reduces the Yes-Associated Protein 1/WW Domain Containing Transcription Regulator 1 Pathway and Prevents Pathologic Remodeling during Bladder Obstruction by Limiting Expression of BDNF.

Chronic bladder obstruction and bladder smooth muscle cell (SMC) stretch provide fibrotic and mechanical environments that can lead to epigenetic change. Therefore, we examined the role of DNA methylation in bladder pathology and transcriptional control. Sprague-Dawley female rats underwent partial bladder obstruction by ligation of a silk suture around the proximal urethra next to a 0.9-mm steel rod. Sham operation comprised passing the suture around the urethra. After 2 weeks, rats were randomized to normal saline or DNA methyltransferase inhibitor, 5-aza-2-deoxycytidine (DAC) at 1 mg/kg, three times/week intraperitoneally. After 6 weeks, bladders were weighed and divided for histology and RNA analysis by high-throughput real-time quantitative PCR arrays. DAC treatment during obstruction in vivo profoundly augmented brain-derived neurotrophic factor (BDNF) expression compared with the obstruction with vehicle group, which was statistically correlated with pathophysiologic parameters. BDNF, cysteine rich angiogenic inducer 61 (CYR61), and connective tissue growth factor (CTGF) expression clustered tightly together using Pearson's correlation analysis. Their promoters were associated with the TEA domain family member 1 (TEAD1) and Yes-associated protein 1/WW domain containing transcription regulator 1 pathways. Interestingly, DAC treatment increased BDNF expression in bladder SMCs (P < 0.0002). Stretch-induced BDNF was inhibited by the YAP/WWTR1 inhibitor verteporfin. Verteporfin improved the SMC phenotype (proliferative markers and SMC marker expression), in part by reducing BDNF. Expression of BDNF is limited by DNA methylation and associated with pathophysiologic changes during partial bladder outlet obstruction and SMC phenotypic change in vitro.

Erratum: "A Case-Control Study of Maternal Polybrominated Diphenyl Ether (PBDE) Exposure and Cryptorchidism in Canadian Populations".

[This corrects the article DOI: 10.1289/EHP522.].

Non-stented versus stented urethroplasty for distal hypospadias repair: A systematic review and meta-analysis.

INTRODUCTION: Studies have shown that non-stented distal hypospadias repair eliminates stent-related bladder spasm and stent removal discomfort without increasing complications; however, results are inconsistent. We performed a systematic review to assess the complication rates of non-stented compared to the stented distal hypospadias repair. METHODS: The literature search included randomized control trials (RCTs) and cohort studies published prior to October 2016 in all languages (PROSPERO CRD42016047563). All included studies were assessed according to Cochrane Collaborative recommendations and included for meta-analysis. Surgical outcomes from each treatment group were classified according to early complications and later final outcomes. Outcomes were expressed as relative risk (RR) and 95% confidence intervals (CI). Interstudy heterogeneity was assessed using chi-square and I2. Effect estimates were pooled using the inverse variant method with random effect model. Subgroup analysis was performed according to surgical technique (Mathieu versus tubularized incised plate) and study design. RESULTS: A total of 20 studies (14 cohorts, 6 RCTs) with 2466 hypospadias repairs (1290 non-stented, 1176 stented) were included for the meta-analysis. Serious risk of bias was noted among the cohort studies with publication bias likely present, while the included RCTs were of moderate methodological quality. The overall pooled effect estimates comparing non-stented versus stented distal hypospadias repair showed no between-group difference for outcomes of early and late complications (RR 0.83, 95% CI 0.46-1.50; RR 0.96, 95% CI 0.92, 1.48; respectively) CONCLUSIONS: Current evidence of low to moderate quality suggests that there is likely no outcome difference between non-stented and stented distal hypospadias repair.

Non-invasive voiding assessment in conscious mice.

OBJECTIVE: To review available options of assessing murine bladder function and to evaluate a non-invasive technique suitable for long-term recording. METHODS: We reviewed previously described methods to record rodent bladder function. We used modified metabolic cages to capture novel recording tracings of mouse micturition. We evaluated our method in a pilot study with female mice undergoing partial bladder outlet obstruction or sham operation, respectively; half of the partial obstruction and sham group received treatment with an S6K-inhibitor, targeting the mTOR pathway, which is known to be implicated in bladder response to obstruction. RESULTS: Our non-invasive method using continuous urine weight recording reliably detected changes in murine bladder function resulting from partial bladder outlet obstruction or treatment with S6K-inhibitor. We found obstruction as well as treatment with S6K-inhibitor to correlate with a hyperactive voiding pattern. CONCLUSIONS: While invasive methods to assess murine bladder function largely disturb bladder histology and intrinsically render post-cystometry gene expression analysis of questionable value, continuous urine weight recording is a reliable, inexpensive, and critically non-invasive method to assess murine bladder function, suitable for a long-term application.

Activated Hedgehog-GLI Signaling Causes Congenital Ureteropelvic Junction Obstruction.

Intrinsic ureteropelvic junction obstruction is the most common cause of congenital hydronephrosis, yet the underlying pathogenesis is undefined. Hedgehog proteins control morphogenesis by promoting GLI-dependent transcriptional activation and inhibiting the formation of the GLI3 transcriptional repressor. Hedgehog regulates differentiation and proliferation of ureteric smooth muscle progenitor cells during murine kidney-ureter development. Histopathologic findings of smooth muscle cell hypertrophy and stroma-like cells, consistently observed in obstructing tissue at the time of surgical correction, suggest that Hedgehog signaling is abnormally regulated during the genesis of congenital intrinsic ureteropelvic junction obstruction. Here, we demonstrate that constitutively active Hedgehog signaling in murine intermediate mesoderm-derived renal progenitors results in hydronephrosis and failure to develop a patent pelvic-ureteric junction. Tissue obstructing the ureteropelvic junction was marked as early as E13.5 by an ectopic population of cells expressing Ptch2, a Hedgehog signaling target. Constitutive expression of GLI3 repressor in Ptch1-deficient mice rescued ectopic Ptch2 expression and obstructive hydronephrosis. Whole transcriptome analysis of isolated Ptch2+ cells revealed coexpression of genes characteristic of stromal progenitor cells. Genetic lineage tracing indicated that stromal cells blocking the ureteropelvic junction were derived from intermediate mesoderm-derived renal progenitors and were distinct from the smooth muscle or epithelial lineages. Analysis of obstructive ureteric tissue resected from children with congenital intrinsic ureteropelvic junction obstruction revealed a molecular signature similar to that observed in Ptch1-deficient mice. Together, these results demonstrate a Hedgehog-dependent mechanism underlying mammalian intrinsic ureteropelvic junction obstruction.