Epigenetic insights to pediatric uropathology: Celebrating the fundamental biology vision of Tony Khoury.

INTRODUCTION: Many pediatric urology conditions affect putatively normal tissues or appear too commonly to be based solely on specific DNA mutations. Understanding epigenetic mechanisms in pediatric urology, therefore, has many implications that can impact cell and tissue responses to settings, such as environmental and hormonal influences on urethral development, uropathogenic infections, obstructive stimuli, all of which originate externally or extracellularly. Indeed, the cell's response to external stimuli is often mediated epigenetically. In this commentary, we highlight work on the critical role that epigenetic machinery, such as DNA methyltransferases (DNMTs), Enhancer of Zeste Polycomb Repressive Complex 2 Subunit (EZH2), and others play in regulating gene expression and cellular functions in three urological contexts. DESIGN: Animal and cellular constructs were used to model clinical pediatric uropathology. The hypertrophy, trabeculation, and fibrosis of the chronically obstructed bladder was explored using smooth muscle cell models employing disorganised vs. normal extracellular matrix (ECM), as well as a new animal model of chronic obstructive bladder disease (COBD) which retains its pathologic features even after bladder de-obstruction. Cell models from human and murine hypospadias or genital tubercles (GT) were used to illustrate developmental responses and epigenetic dependency of key developmental genes. Finally, using bladder urothelial and organoid culture systems, we examined activity of epigenetic machinery in response to non uropathogenic vs. uropathogenic E.coli (UPEC). DNMT and EZH2 expression and function were interrogated in these model systems. RESULTS: Disordered ECM exerted a principal mitogenic and epigenetic role for on bladder smooth muscle both in vitro and in CODB in vivo. Key genes, e.g., BDNF and KCNB2 were under epigenetic regulation in actively evolving obstruction and COBD, though each condition showed distinct epigenetic responses. In models of hypospadias, estrogen strongly dysregulated WNT and Hox expression, which was normalized by epigenetic inhibition. Finally, DNA methylation machinery in the urothelium showed specific activation when challenged by uropathogenic E.coli. Similarly, UPEC induces hypermethylation and downregulation of the growth suppressor p16INK4A. Moreover, host cells exposed to UPEC produced secreted factors inducing epigenetic responses transmissible from one affected cell to another without ongoing bacterial presence. DISCUSSION: Microenvironmental influences altered epigenetic activity in the three described urologic contexts. Considering that many obstructed bladders continue to display abnormal architecture and dysfunction despite relief of obstruction similar to after resection of posterior valves or BPH, the epigenetic mechanisms described highlight novel approaches for understanding the underlying smooth muscle myopathy of this crucial clinical problem. Similarly, there is evidence for an epigenetic basis of xenoestrogen on development of hypospadias, and UTI-induced pan-urothelial alteration of epigenetic marks and propensity for subsequent (recurrent) UTI. The impact of mechanical, hormonal, infectious triggers on genitourinary epigenetic machinery activity invite novel avenues for targeting epigenetic modifications associated with these non-cancer diseases in urology. This includes the use of deactivated CRISPR-based technologies for precise epigenome targeting and editing. Overall, we underscore the importance of understanding epigenetic regulation in pediatric urology for the development of innovative therapeutic and management strategies.

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.

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.

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.

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.

Impact of Adjuvant Urinary Diversion versus Valve Ablation Alone on Progression from Chronic to End Stage Renal Disease in Posterior Urethral Valves: A Single Institution 15-Year Time-to-Event Analysis.

PURPOSE: Long-term progression to end stage renal disease of valve ablation alone vs ablation followed by additional urinary diversion were compared among children with stage 3 chronic kidney disease due to posterior urethral valves. MATERIALS AND METHODS: We performed a retrospective study of children with posterior urethral valves and stage 3 chronic kidney disease treated at a single institution between 1986 and 2011. The 3 treatment groups were classified as group 1-valve ablation alone, group 2-ablation plus subsequent vesicostomy and group 3-ablation followed by ureterostomies and/or pyelostomies. Baseline demographic characteristics were analyzed. Statistical analyses compared the incidence of time to end stage renal disease among the intervention groups using the Fisher-Freeman-Halton exact test and Kaplan-Meier analysis with the log rank test. Cox regression was used to determine predictors of end stage renal disease progression. RESULTS: A total of 40 eligible patients were included in the study (group 1-14 patients, group 2-13 patients, group 3-13 patients). Baseline characteristics and post-intervention estimated glomerular filtration rate revealed no significant between-group differences. A statistically significant difference in progression to end stage renal disease was noted within 1 year after diagnosis of stage 3 chronic kidney disease among the treatment groups (log rank test p=0.02). However, cumulative end stage renal disease incidence at 15-year followup showed no statistical difference (log rank test p=0.628). Cox regression analysis determined that bilateral renal dysplasia (HR 2.76, 95% CI 1.21-6.30) and estimated glomerular filtration rate 60 ml/minute/1.73 m2 or greater after intervention (HR 0.23, 95% CI 0.09-0.61) were predictive of the likelihood of progression to end stage renal disease. CONCLUSIONS: Urinary diversion following valve ablation in children with stage 3 chronic kidney disease associated with posterior urethral valves may temporarily delay progression to end stage renal disease. However, no long-term benefit was noted from diversion in the ultimate incidence of end stage renal disease, suggesting that these interventions should be seen as a temporizing measure. Bilateral renal dysplasia and post-intervention estimated glomerular filtration rate are independent variables predicting overall chronic kidney disease progression.

Utilization of Postpenile Surgery Illustrated Healing Atlas: A Comparative Study.

OBJECTIVE: To determine the effect of the postpenile surgery illustrated healing atlas on caregivers' anxiety levels pre- and postoperatively, the frequency of family's postoperative communication with the urology care team, and the number of unplanned emergency room (ER) return for wound checks. METHODS: A prospective cohort enrolled children who underwent penile surgeries (distal hypospadias repair and phalloplasty) with no concomitant procedures from December 2016 to June 2017. A 6-item short-form Spielberger State-Trait Anxiety Inventory (STAI) was used to determine baseline and postoperative anxiety levels of the caregivers. Two groups were created: caregivers who did not view the illustrated atlas vs caregivers who were shown the atlas. Baseline characteristics and demographics were compared, along with caregiver's pre- to postoperative anxiety level difference, frequency of postoperative communication, and number of unplanned ER return for wound checks. RESULTS: Fifty-four patients were enrolled with 27 families in each group. Baseline characteristics and demographics were comparable with no significant differences. The assessment of the pre- to postoperative anxiety levels in both groups showed no significant differences (median difference -5 [interquartile range -8 to -5] vs -5 [interquartile range -8 to -4], P = .94). Although no differences were noted for ER-return rates between the groups (18% vs 11.1%, P = .704), significantly less postoperative calls and e-mails were noted among families who received or viewed the postpenile surgery illustrated healing atlas (51.9% vs 11.1%, P = .003). CONCLUSION: The utilization of a postpenile surgery illustrated healing atlas as part of the postoperative support provided to families was able to decrease postoperative calls and e-mails.

ECLAMC Study: prevalence patterns of hypospadias in South America: multi-national analysis over a 24-year period

ABSTRACT Objective To evaluate prevalence trends of hypospadias in South-America it is essential to perform multicenter and multinational studies with the same methodology. Herein we present systematic data as part of an international multicenter initiative evaluating congenital malformations in South America over a 24-year period. Materials and Methods A nested case-control study was conducted using the Latin American Collaborative Study of Congenital Malformations (ECLAMC), between January 1989 and December 2012. Cases were stratified as isolated (IH) and non-isolated hypospadias (NIH). Global prevalence was calculated and discriminated by country. Associations between birth weight and gestational age, and NIH distribution by associated abnormality and severity of hypospadias, were analyzed. Results A total of 159 hospitals from six countries participated, reporting surveillance on 4.020.384 newborns. A total of 4.537 hypospadias cases were detected, with a global prevalence of 11.3/10.000 newborns. Trend analyses showed in Chile, Brazil and Uruguay a statistically significant increase in prevalence. Analysis of severity and associated anomalies did not to find an association for distal cases, but did for proximal (RR=1.64 [95% CI=1.33-2.03]). Conclusion This is one of only a few Latin American multicenter studies reporting on the epidemiology of hypospadias in South America in the last two decades. Our data adds to evidence suggesting an increase in some countries in the region at different times. There were also variations in prevalence according to severity. This study adds to literature describing associated anomalies at a hospital-based level.

Application of the STROBE statement to the hypospadias literature: Report of the international pediatric urology task force on hypospadias.

INTRODUCTION: Observational studies, particularly case series, represent the majority of the current hypospadias research. As a result, this literature lacks standardization of surgical techniques, uniform definitions of hypospadias complications, and consistency of outcome reporting, which may make it difficult to compare results across studies. A modified version of the STROBE statement, containing 20 items, was presented at the International Pediatric Urology Task Force on Hypospadias meeting to assist with clear and transparent reporting of hypospadias studies. The adoption and implementation of this modified tool will allow investigators and health care providers to critically evaluate quality and identify bias within the literature. In addition this instrument will ensure consistency of reporting, improving objective comparisons between studies, unification of results, and development of evidence-based clinical guidelines. METHODS: In this article, we have applied the modified STROBE statement to the hypospadias literature, aiming to create a guide on study reporting for pediatric urologists, and ultimately improve the quality of research in our field. We present itemized recommendations for adequate reporting of hypospadias studies and case series, ranging from drafting the abstract to addressing biases and potential sources of confounding. Included with each item is a brief explanation of its importance and potential effect on the study, as well as pertinent examples of hypospadias articles. RESULTS: A modified STROBE summary table containing 20 items is presented in (Supplementary Table 1). CONCLUSIONS: If properly conducted and reported, hypospadias studies have the potential to provide useful information to clinicians and surgeons. However, authors should recognize the inherent limitations of these observational studies, especially in the form of bias, which may introduce invalid data or limit generalizability. Thus, we expect that the use of this guiding tool will not only improve transparency of hypospadias reporting, but also improve its methodological quality, allowing proper comparison and interpretation of data across different institutions.

Uropathogenic E. coli (UPEC) Infection Induces Proliferation through Enhancer of Zeste Homologue 2 (EZH2).

UNLABELLED: Host-pathogen interactions can induce epigenetic changes in the host directly, as well as indirectly through secreted factors. Previously, uropathogenic Escherichia coli (UPEC) was shown to increase DNA methyltransferase activity and expression, which was associated with methylation-dependent alterations in the urothelial expression of CDKN2A. Here, we showed that paracrine factors from infected cells alter expression of another epigenetic writer, EZH2, coordinate with proliferation. Urothelial cells were inoculated with UPEC, UPEC derivatives, or vehicle (mock infection) at low moi, washed, then maintained in media with Gentamycin. Urothelial conditioned media (CM) and extracellular vesicles (EV) were isolated after the inoculations and used to treat naïve urothelial cells. EZH2 increased with UPEC infection, inoculation-induced CM, and inoculation-induced EV vs. parallel stimulation derived from mock-inoculated urothelial cells. We found that infection also increased proliferation at one day post-infection, which was blocked by the EZH2 inhibitor UNC1999. Inhibition of demethylation at H3K27me3 had the opposite effect and augmented proliferation. CONCLUSION: Uropathogen-induced paracrine factors act epigenetically by altering expression of EZH2, which plays a key role in early host cell proliferative responses to infection.

Inappropriate Use of Ultrasound in Management of Pediatric Cryptorchidism.

BACKGROUND AND OBJECTIVES: There is a limited role for ultrasound in the management of an undescended testicle (UDT). We hypothesized that ultrasound remains overused by referring physicians. Our goal was to characterize the trends, patterns, and impact of ultrasound use for UDT and to reaffirm its limited diagnostic value for this indication. METHODS: The records of boys aged 0 to 18 years with UDT in Ontario, Canada, between 2000 and 2011 were reviewed by using health administrative data housed at the Institute for Clinical and Evaluative Sciences (ICES). A second review of boys referred to our institution with UDT between 2007 and 2011 was conducted to complement the health administrative data. Trends in frequency, distribution, and costs of ultrasound use were assessed. Time delays between diagnosis and definitive management were compared between the ultrasound and non-ultrasound groups. Using our institutional data, we analyzed demographic patterns of ultrasound use and compared its diagnostic accuracy by using surgical findings as the gold standard. RESULTS: Ultrasound was used in 33.5% of provincial referrals and 50% of institutional referrals. Children who underwent ultrasound experienced an approximate 3-month delay in definitive surgical management. Ultrasound correctly predicted physical examination findings in only 54% of patients. Physicians in community practice, and those with fewer years in practice, were more likely to order ultrasound. CONCLUSIONS: Ultrasound has limited value for the management of UDT but remains widely overused, with an increasing trend over time. This practice has negative implications for access to care and cost-containment. Widespread educational efforts should be undertaken, targeting current and future referring physicians.

The burden of attending a pediatric surgical clinic and family preferences toward telemedicine.

BACKGROUND/PURPOSE: Indirect expenses for accessing health care may place significant fiscal strain on Canadian families. Telemedicine alternatives, using email, telephone, and video conferencing, can mitigate such financial burdens by reducing travel and related costs. Our objectives were to assess costs that families incur visiting an outpatient pediatric surgical clinic, and family attitudes toward telemedicine alternatives. METHODS: A survey was offered pre-consult to all families who attended pediatric urology and general surgery outpatient clinics over a three-month period. RESULTS: A total of 1032 of 1574 families screened participated (66.0%). Less than half (18.5%) of participants traveled over 200 km, and 32.9% spent over 4 hours in transit, round-trip. The proportion of participants who spent over $50 on travel and ancillary expenses was 33.0%. In 74.0% of families, 1 or more adults missed work. The proportion of families who perceived costs as somewhat high or high was 29.1%. Perceived cost was positively correlated to distance traveled, money spent, and missed work (p<0.01). Most were comfortable with medical communication using technology; and 34.3%-42.7% would avoid an in-person clinic visit utilizing email, telephone, and video conferencing. Higher perceived cost (p<0.001) and distance traveled (p<0.01) were only weakly associated with greater willingness to substitute a clinic visit with video conferencing. CONCLUSIONS: Many families face high costs related to routine outpatient clinical visits, and there is a substantial willingness by them to access telemedicine alternatives, rather than the traditional face-to-face clinical visit.

A comprehensive review of pediatric urachal anomalies and predictive analysis for adult urachal adenocarcinoma.

PURPOSE: We examined the presentation, diagnosis and management of radiologically detected pediatric urachal anomalies and assessed the risk of malignant degeneration. MATERIALS AND METHODS: Our radiology database (2000 to 2012) was queried for all children younger than 18 years who were diagnosed with a urachal anomaly radiographically, and the operative database was used to determine those who underwent excision. Data collected included demographics, presenting symptoms, imaging modality and indication for excision. These data were compared to the Ontario Cancer Registry to determine the risk of malignancy. RESULTS: A total of 721 patients were radiographically diagnosed with a urachal anomaly (667 incidentally), yielding a prevalence of 1.03% of the general pediatric population. Diagnoses were urachal remnants (89% of cases), urachal cysts (9%) and patent urachus (1.5%). Ultrasonography was the most common imaging modality (92% of cases), followed by fluoroscopy/voiding cystourethrography (5%) and computerized tomography/magnetic resonance imaging (3%). A total of 61 patients (8.3%) underwent surgical excision. Indications for imaging and treatment were umbilical drainage (43% of patients), abdominal pain (28%), palpable mass (25%) and urinary tract infection (7%). Mean age at excision was 5.6 years and 64% of the patients were male. Based on provincial data, the number needed to be excised to prevent a single case of urachal adenocarcinoma was 5,721. CONCLUSIONS: Urachal anomalies are more common than previously reported. Children with asymptomatic lesions do not appear to benefit from prophylactic excision, as the risk of malignancy later in life is remote and a large number of urachal anomalies would need to be removed to prevent a single case of urachal adenocarcinoma.

NOTch just a bladder control problem.

Human bladder cancers harbor deletions and point mutations in genes coding for Notch receptors and proteins involved in Notch signaling. This leads to elevated MAPK pathway activation, as direct Notch-mediated transcription of MAPK phosphatase DUSP is lost. These bladder tumors, with impaired Notch signaling, also show basal differentiation.

Decisional regret after distal hypospadias repair: single institution prospective analysis of factors associated with subsequent parental remorse or distress.

PURPOSE: Hypospadias repair is a commonly performed procedure. Little is known about decisional regret in parents who agree to proceed with this surgical reconstruction. We present data on this previously underexplored issue. MATERIALS AND METHODS: We performed followup analysis of 100 couples prospectively evaluated after counseling for surgical correction of distal hypospadias in their son with assessment of complications and decisional regret 1 year after surgery. Findings were contrasted with baseline demographics, hypospadias knowledge and decisional conflict at the time of counseling. RESULTS: Decisional regret was found in 116 parents, including mild regret in 41.4% and moderate to severe regret in 8.6%. There was no statistically significant difference in paired regret analysis between mothers and fathers. Complications were strongly associated with decisional regret (p <0.001). On regression analysis postoperative complications (OR 14.7, 95% CI 1.6-131.6), parental desire to avoid circumcision (OR 7.4, 95% CI 1.1-49.4) and initial decisional conflict level (OR 1.06, 95% CI 1.02-1.09) were statistically significant predictors of moderate to strong decisional regret. These findings remained robust after imputation strategies to address missing data. The impact of decisional conflict and preference for circumcision were significant even after excluding families who experienced complications. CONCLUSIONS: To our knowledge this is the first study demonstrating parental decisional regret after providing consent for surgical correction of distal hypospadias in their son. Based on the described risk factors efforts aimed at minimizing complications and counseling about foreskin preservation techniques may be prudent to ameliorate decisional regret. The novel association between decisional conflict and regret suggests that conflict assessment during counseling may help screen families at risk for postoperative regret.

Reduced flow after tubularized incised plate urethroplasty--increased fibrogenesis, elastin fiber loss or neither?

PURPOSE: Low urinary flow rates are common after tubularized incised plate urethroplasty but the etiology remains unclear and may be related to low urethral compliance due to abnormal collagen concentrations and/or fewer elastic fibers in the healed urethral plate. We hypothesized that inserting a preputial mucosal graft over the dorsal raw area after the midline incision may avoid scarring and improve urethral compliance. MATERIALS AND METHODS: Adult rabbits were submitted to tubularized incised plate urethroplasty with or without inlay preputial graft according to a previously described protocol. Tissular concentrations of collagens I, III, IV, VI, VIII and XIII were measured. Histomorphometric analysis was used to quantify elastic fibers in the urethra. Tubularized incised plate urethroplasty with and without inlay preputial graft was compared to normal rabbit urethras (controls). RESULTS: mRNA concentrations for collagens I, II and XIII were similar between controls and operated rabbits. The proportions between collagens I and III were 1.05, 0.87 and 1.21, respectively, in controls and animals undergoing tubularized incised plate urethroplasty with and without inlay preputial graft. mRNA concentrations for collagen IV and collagens VI/VIII tended to be higher and lower, respectively, in the operated urethras, despite showing statistical significance only for collagen VIII in animals undergoing tubularized incised plate urethroplasty with inlay preputial graft vs controls (p=0.02). The operated animals did not demonstrate a reduced number of elastic fibers in the urethral tissues compared to controls. CONCLUSIONS: Elastic fiber number and distribution were similar between tubularized incised plate urethroplasty cases and controls, suggesting that decreased concentrations of elastic fibers do not explain the reduced urethral compliance after tubularized incised plate urethroplasty. The raw area determined by the dorsal urethral incision regenerated after standard tubularized incised plate urethroplasty, while cicatrization with fibrosis occurred in correspondence to the grafted areas after tubularized incised plate urethroplasty with inlay preputial graft.

Failed pyeloplasty in children: revisiting the unknown.

OBJECTIVE: To perform a critical analysis of the management of the pediatric failed pyeloplasty in a large tertiary center. The ideal approach to this rare entity is not well established. METHODS: Retrospective record review of children undergoing pyeloplasty from 2000 to 2010. All cases that required any type of reintervention, excluding stent removal, were analyzed. Data collected included: demographics, indication for and modality of the initial surgery, presence of crossing vessels, mode of diagnosis of failure, and type(s) of reintervention with the correspondent success rate(s). RESULTS: Overall, pyeloplasty failure rate was 27 per 455 patients (5.9%). Age, initial indication for pyeloplasty, and modality of surgery (open vs laparoscopic) yielded similar failure rates. Indications for reintervention were as follows: worsening asymptomatic hydronephrosis 16 of 27 (59%), pain 7 of 27 (26%), urosepsis 2 of 27 (7.5%), and others 2 of 27 (7.5%). Eight of 27 (30%) improved with 1, 14 of 27 (52%) had 2, and 5 of 27 (18%) required 3 reinterventions, respectively. Mean interval between the first operation and subsequent interventions was 19.3, 24.9, and 27 months for the first, second, and third reinterventions, respectively. Modalities of reintervention with respective success rates were as follows: double J stent insertion 16% (6%), endopyelotomy 18% (50%), redo pyeloplasty 12% (92%), and ureterocalicostomy 4% (100%). Only 1 patient (7%) was documented to have a missed crossing vessel. All patients were stable and doing well after a mean follow-up of 56 months after the first operation. CONCLUSION: According to this series, more invasive and definitive techniques, such as redo pyeloplasty and ureterocalicostomy, are more successful than minimally invasive ones to treat failed pyeloplasty and should probably be offered sooner rather than later.