Publications by authors named "Darius J Bagli"

112 Publications

Transitional care and a lesson from the pandemic.

J Pediatr Urol 2021 Jan 25. Epub 2021 Jan 25.

Division of Urology, University of Toronto, Sickkids Hospital, Canada; Department of Surgery, University of Toronto, Sickkids Hospital, Canada; University of Toronto, Sickkids Hospital, Canada.

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http://dx.doi.org/10.1016/j.jpurol.2021.01.026DOI Listing
January 2021

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

Pediatr Surg Int 2021 Jan 2;37(1):161-167. Epub 2020 Nov 2.

Division of Urology, Department of Surgery, University of Toronto, Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.

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.
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http://dx.doi.org/10.1007/s00383-020-04770-5DOI Listing
January 2021

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

Can J Surg 2020 03 27;63(2):E155-E160. Epub 2020 Mar 27.

From the Department of Urology and Pediatric Urology, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, Germany (Schröder); and the Department of Urology, Hospital for Sick Children, Toronto, Ont. (Farhat, Bägli, Lorenzo, Koyle).

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.
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http://dx.doi.org/10.1503/cjs.009119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828955PMC
March 2020

Persistent myopathy despite release of partial obstruction: in vivo reversal of dysfunction and transcriptional responses using rapamycin.

FASEB J 2020 03 27;34(3):3594-3615. Epub 2020 Jan 27.

Urology Division, Department of Surgery, Hospital for Sick Children, Toronto, ON, Canada.

Current and potential medical therapy for obstruction-induced myopathic bladder dysfunction (from benign prostatic hyperplasia or posterior urethral valves) focuses on symptoms. The persistent tissue pathology and dysfunction after release of obstruction is often deemed irreversible without any systematic therapeutic approaches. As rapamycin can attenuate bladder smooth muscle hypertrophy and dysfunction during the genesis of partial obstruction in vivo, we tested whether rapamycin could improve persistent function after release of obstruction (de-obstruction or REL). Female Sprague-Dawley rat bladders were partially obstructed (PBO) by suturing around both the urethra and a para-urethral steel rod, then removing the rod. One day prior to release of obstruction (preREL), voiding parameters and residual urine volume of preREL+future rapa, preREL+future veh groups were recorded. Release of obstruction (REL) was performed by suture removal following 6 weeks of PBO. For 4 more weeks after the de-obstruction, REL animals were randomized to rapamycin (REL+rapa) or vehicle (REL+veh). PBO for 6 weeks were used as positive controls. In shams, the urethra was exposed, but no suture tied. Voiding parameters and residual urine volume were measured prior to sacrifice of sham and REL+veh or REL+rapa, and PBO. Rapamycin efficacy was tested by pair-wise comparison of changes in individual voiding data from preREL+future veh or preREL+future rapa versus REL+veh or REL+rapa, respectively, as well as by comparisons of REL+veh to REL+rapa groups. Bladders were weighed and processed for a high-throughput QPCR array, and histopathology. Bladder/body mass ratios with PBO increased significantly and remained higher in the release phase in REL+veh animals. REL+rapa versus REL+veh improved residual volumes and micturition fractions toward sham levels. Three genes encoding extracellular proteins, BMP2, SOD3, and IGFBP7, correlated with functional improvement by Pearson's correlations. The promoters of these genes showed enrichment for several motifs including circadian E-boxes. While obstruction and REL augmented CLOCK and NPAS2 expression above sham levels, rapamycin treatment during release significantly blocked their expression. This experimental design of pharmaco-intervention during the de-obstruction phase revealed a novel pathway dysregulated during the clinically relevant treatment phase of obstructive bladder myopathy.
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http://dx.doi.org/10.1096/fj.201900547RRDOI Listing
March 2020

Normothermic Ex Vivo Kidney Perfusion Improves Early DCD Graft Function Compared With Hypothermic Machine Perfusion and Static Cold Storage.

Transplantation 2020 05;104(5):947-955

Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada.

Background: Better preservation strategies for the storage of donation after circulatory death grafts are essential to improve graft function and to increase the kidney donor pool. We compared continuous normothermic ex vivo kidney perfusion (NEVKP) with hypothermic anoxic machine perfusion (HAMP) and static cold storage (SCS) in a porcine kidney autotransplantation model.

Methods: Porcine kidneys were exposed to 30 minutes of warm ischemia and then reimplanted following either 16 hours of either SCS, HAMP (LifePort 1.0), or NEVKP before autotransplantation (n = 5 per group). The contralateral kidney was removed. Animals were followed for 8 days.

Results: Grafts preserved by NEVKP demonstrated improved function with more rapid recovery compared with HAMP and SCS (mean peak serum creatinine: 3.66 ± 1.33 mg/dL [postoperative d 1 [(POD1)], 8.82 ± 3.17 mg/dL [POD2], and 12.90 ± 2.19 mg/dL [POD3], respectively). The NEVKP group demonstrated significantly increased creatinine clearance calculated on POD3 (63.6 ± 19.0 mL/min) compared with HAMP (13.5 ± 10.3 mL/min, P = 0.001) and SCS (4.0 ± 2.6 mL/min, P = 0.001). Histopathologic injury scores on POD8 were lower in both perfused groups (NEVKP and HAMP, score: 1-1.5) compared with SCS (score: 1-3, P = 0.3), without reaching statistical significance.

Conclusions: NEVKP storage significantly improved early kidney function compared with both cold preservation strategies, although HAMP also demonstrates improvement over SCS. NEVKP may represent a novel, superior preservation option for donation after circulatory death renal grafts compared with conventional hypothermic methods.
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http://dx.doi.org/10.1097/TP.0000000000003066DOI Listing
May 2020

Over-reliance on P Values in Urology: Fragility of Findings in the Hydronephrosis Literature Calls for Systematic Reporting of Robustness Indicators.

Urology 2019 Nov 30;133:204-210. Epub 2019 Jul 30.

Division of Urology, Hospital for Sick Children and Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Objective: To review the robustness of hydronephrosis literature with the application of fragility index (FI) and fragility quotient (FQ) calculations.

Methods: A literature review was conducted using Pubmed, Medline, and Ovid for "hydronephrosis" and associated terms and we included all studies with at least 2 groups being compared. FI was calculated by populating study results into a 2-by-2 contingency table and generating a P value using Fisher's exact test. Next, events were manually added to the group with the fewest events, while removing a nonevent from the same group and Fisher's exact test repeated until the P value was >.05. FQ was calculated by dividing FI by the total sample size.

Results: The 130 included articles were published between 1986 and 2018 in 32 journals. Median citation count was 14 (0-252), 30% were RCTs and most papers originated in the United States (28%), Turkey(10%), and Canada(9%). Median FI was 2 (1-112), FQ was 0.023 (0.0010-0.55), and 60 papers (46%) had a FI of 1, indicating extremely fragile results. There was a significant difference in the FI between observational studies and RCTs (10 ± 17 vs 4 ± 5; P = .02); however, there was no difference in FQ (0.032 ± 0.030 vs 0.053 ± 0.080; P = .09) between them.

Conclusion: Nearly half of studies in hydronephrosis literature reporting significant results are extremely fragile, requiring addition of only a couple of events in 1 treatment arm to significantly modify the results. As such, objective reporting of robustness of results should include FI and FQ which may help diminish over-reliance on P values as the main indicator of clinical significance in comparative studies.
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http://dx.doi.org/10.1016/j.urology.2019.03.045DOI Listing
November 2019

Idiopathic Urinary Bladder Perforation in Early Childhood.

Kidney Int Rep 2018 Nov 3;3(6):1497-1500. Epub 2018 Aug 3.

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1016/j.ekir.2018.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224671PMC
November 2018

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.

Am J Pathol 2018 10 17;188(10):2177-2194. Epub 2018 Aug 17.

Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; Urology Division, Department of Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Physiology, Faculty of Arts and Sciences, University of Toronto, Toronto, Ontario, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ajpath.2018.06.024DOI Listing
October 2018

Non-invasive voiding assessment in conscious mice.

Bladder (San Franc) 2018 2;5(2):e33. Epub 2018 Apr 2.

The Hospital for Sick Children, Research Institute, Developmental and Stem Cell Biology, Toronto, Canada.

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.
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http://dx.doi.org/10.14440/bladder.2018.582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401987PMC
April 2018

Activated Hedgehog-GLI Signaling Causes Congenital Ureteropelvic Junction Obstruction.

J Am Soc Nephrol 2018 02 6;29(2):532-544. Epub 2017 Nov 6.

Program in Developmental and Stem Cell Biology,

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 , a Hedgehog signaling target. Constitutive expression of GLI3 repressor in deficient mice rescued ectopic expression and obstructive hydronephrosis. Whole transcriptome analysis of isolated 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 -deficient mice. Together, these results demonstrate a Hedgehog-dependent mechanism underlying mammalian intrinsic ureteropelvic junction obstruction.
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http://dx.doi.org/10.1681/ASN.2017050482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791051PMC
February 2018

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.

J Urol 2018 03 20;199(3):824-830. Epub 2017 Oct 20.

Division of Urology, The Hospital for Sick Children and Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Electronic address:

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 m 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.
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http://dx.doi.org/10.1016/j.juro.2017.10.024DOI Listing
March 2018

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

Urology 2018 Feb 12;112:151-154. Epub 2017 Oct 12.

Division of Urology, The Hospital for Sick Children, Toronto, ON, Canada.

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.
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http://dx.doi.org/10.1016/j.urology.2017.10.001DOI Listing
February 2018

Nerve-sparing Mid-urethral Obstruction (NeMO) in Female Small Rodents.

J Vis Exp 2017 04 25(122). Epub 2017 Apr 25.

Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children; Institute of Medical Science, University of Toronto; Pediatric Urology, The Hospital for Sick Children.

Partial bladder outlet obstruction (pBOO) has a high prevalence, causes significant patient burden, and immense health care costs. The most common animal model to investigate bladder remodeling in pBOO are female rodents undergoing partial obstruction at the proximal urethra. Variability in the degree of obstruction and animal mortality are major concerns with proximal obstruction. Furthermore, dissecting around the proximal urethra and bladder neck jeopardizes bladder innervation. We developed a nerve-sparing mid-urethral obstruction (NeMO) model for pBOO avoiding the disadvantages of the traditional model. We approached the urethra just inferior to the pubic symphysis, which obviated the need for laparotomy as well as for dissection in this area; also, the striated urethral sphincter remained untouched. We performed NeMO in female Sprague-Dawley rats (12 obstructions, 6 sham animals) as well as in female C57/bl6 mice (20 obstructions, 18 sham animals). After two weeks, we evaluated bladder function, bladder mass, and body mass. We had no mortalities among obstructed- or sham-operated female rats; as described for the traditional proximal pBOO-method, we tied the suture around the proximal urethra and a temporarily placed 0.9 mm metal rod. NeMO induced an 85% increase in bladder mass after two weeks, average residual urine volume was 0.4 mL in partially obstructed rats while only 0.03 mL in sham animals. In mice, we tested 3 sizes of cannulas that we placed along the urethra when tying the suture. We found that using a 27-gauge cannula resulted in over 50% animal mortality; placing the 25-gauge cannula did not yield the desired response in increasing bladder mass; utilizing a 26-gauge cannula yielded favorable results with minimal animal mortality (1/8) yet a significant 2-fold increase in bladder mass.
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http://dx.doi.org/10.3791/55288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565093PMC
April 2017

Finding NeMO-Nerve-sparing Mid-urethral Obstruction: A Pathophysiologically Accurate Model of Rodent Partial Bladder Outlet Obstruction.

Urology 2017 Jul 30;105:208.e1-208.e9. Epub 2017 Mar 30.

Division of Urology, The Hospital for Sick Children, Toronto, ON, Canada; Institute of Medical Science, and Department of Surgery, University of Toronto, Toronto, ON, Canada; Research Institute, Division of Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address:

Objective: To develop and evaluate a novel technique modeling partial bladder outlet obstruction (pBOO) using a nerve-sparing mid-urethral obstruction (NeMO) approach.

Materials And Methods: Female unoperated rats were compared to rats after NeMO, NeMO sham, proximal urethral (PU) obstruction, or PU sham. Residual volume, bladder capacity, voiding volume, and bladder mass were recorded; the contractile characteristics of isolated bladder strips were also analyzed. Additionally, we quantitated nerve fibers at the bladder neck as well as the extracellular matrix in the bladder wall.

Results: NeMO yields a more predictable degree of obstruction vs PU, causes no animal mortality, and is easy to release. NeMO also results in a more moderate increase in bladder mass commensurate with human disease vs the exaggerated response to PU, and does not lead to the excessive bladder dilation observed after PU while showing increased residual urine and fibrosis over time, thus closely modeling human pBOO pathophysiology. Importantly, PU shams significantly incite both an undesirable mass increase as well as bladder dysfunction, correlating with a denervation injury making them unsuitable as controls when modeling a non-neurogenic pBOO. The bladder physiology and structure of NeMO-sham animals were indistinguishable from those of unoperated controls. The low complication rate and low variability of NeMO also can be applied to mice, opening the pBOO field to the full spectrum of transgenic manipulation.

Conclusion: NeMO is a pathophysiologically accurate modeling approach, with low variability and mortality, and newly paves the way for realistic and robust interpretation of omics and sequencing analytical methodologies. We therefore suggest NeMO as a new standard model when investigating pBOO.
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http://dx.doi.org/10.1016/j.urology.2017.03.032DOI Listing
July 2017

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

J Pediatr Urol 2016 Dec 22;12(6):367-380. Epub 2016 Aug 22.

Division of Urology, Hasbro Children's Hospital, Brown University, Providence, RI, USA.

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.
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http://dx.doi.org/10.1016/j.jpurol.2016.05.048DOI Listing
December 2016

ECLAMC Study: Prevalence patterns of hypospadias in South America: Multi-national analysis over a 24-year period.

Int Braz J Urol 2017 Mar-Apr;43(2):325-334

Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá, Colombia.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433373PMC
http://dx.doi.org/10.1590/S1677-5538.IBJU.2016.0002DOI Listing
August 2017

Preparation With Web-Based Observational Practice Improves Efficiency of Simulation-Based Mastery Learning.

Simul Healthc 2016 Oct;11(5):316-322

From the Wilson Centre (J.J.H.C.), Faculty of Medicine, University of Toronto; SickKids Learning Institute (J.J.H.C.), The Hospital for Sick Children, Toronto, ON, Canada; Changi Simulation Institute (J.K.), Changi General Hospital, Singapore, Singapore; Department of Curriculum (C.B.), Teaching and Learning, Ontario Institute for Studies in Education, University of Toronto; Department of Surgery (D.J.B.), University of Toronto, Toronto; Faculty of Business and Information Technology (B.K.), University of Ontario Institute of Technology, Oshawa; and Discipline of Emergency Medicine (A.D.), Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.

Introduction: Our current understanding of what results in effective simulation-based training is restricted to the physical practice and debriefing stages, with little attention paid to the earliest stage: how learners are prepared for these experiences. This study explored the utility of Web-based observational practice (OP) -featuring combinations of reading materials (RMs), OP, and collaboration- to prepare novice medical students for a simulation-based mastery learning (SBML) workshop in central venous catheterization.

Methods: Thirty medical students were randomized into the following 3 groups differing in their preparatory materials for a SBML workshop in central venous catheterization: a control group with RMs only, a group with Web-based groups including individual OP, and collaborative OP (COP) groups in addition to RM. Preparation occurred 1 week before the SBML workshop, followed by a retention test 1-week afterward. The impact on the learning efficiency was measured by time to completion (TTC) of the SBML workshop. Web site preparation behavior data were also collected.

Results: Web-based groups demonstrated significantly lower TTC when compared with the RM group, (P = 0.038, d = 0.74). Although no differences were found between any group performances at retention, the COP group spent significantly more time and produced more elaborate answers, than the OP group on an OP activity during preparation.

Discussion: When preparing for SBML, Web-based OP is superior to reading materials alone; however, COP may be an important motivational factor to increase learner engagement with instructional materials. Taken together, Web-based preparation and, specifically, OP may be an important consideration in optimizing simulation instructional design.
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http://dx.doi.org/10.1097/SIH.0000000000000171DOI Listing
October 2016

Eight-Hour Continuous Normothermic Ex Vivo Kidney Perfusion Is a Safe Preservation Technique for Kidney Transplantation: A New Opportunity for the Storage, Assessment, and Repair of Kidney Grafts.

Transplantation 2016 Sep;100(9):1862-70

1 Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. 2 Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada. 3 Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 4 Department of General, Visceral and Transplantation Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstr, Mainz, Germany. 5 Programa de Doctorat en Medicina de la Universitat Autònoma de Barcelona, Barcelona, Spain. 6 Laboratory Medicine and Pathobiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. 7 Departments of Surgery (Urology) & Physiology, The Hospital for Sick Children, Toronto, Ontario, Canada. 8 Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Background: Hypothermic kidney storage causes preservation injury and is poorly tolerated by renal grafts. We investigated whether static cold storage (SCS) can be safely replaced with a novel technique of pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) in heart-beating donor kidney transplantation.

Methods: Right kidneys were removed from 30 kg Yorkshire pigs in a model of heart-beating donation and either preserved in cold histidine-tryptophan-ketoglutarate solution for 8 hours (n = 5), or subjected to 8 hours of pressure-controlled NEVKP (n = 5) followed by renal heterotopic autotransplantation.

Results: During NEVKP, physiologic perfusion conditions were maintained with low intrarenal resistance and normal electrolyte and pH parameters. Aspartate aminotransferase and lactate dehydrogenase as injury markers were below the detectable analyzer range (<4 and <100 U/L, respectively). Perfusate lactate concentration decreased from baseline until the end of perfusion (10.38 ± 0.76 mmol/L vs 1.22 ± 0.26 mmol/L; P < 0.001). Posttransplantation, animals transplanted with NEVKP versus SCS grafts demonstrated similar serum creatinine peak levels (NEVKP, 2.0 ± 0.5 vs SCS 2.7 ± 0.7 mg/dL; P = 0.11) and creatinine clearance on day 10 (NEVKP, 65.9 ± 18.8 mL/min vs SCS 61.2 ± 15.6 mL/min; P = 0.74). After 10 days of follow-up, animals transplanted with NEVKP grafts had serum creatinine and blood urea nitrogen values comparable to their basal levels (P = 0.49 and P = 0.59), whereas animals transplanted with SCS grafts had persistently elevated serum creatinine and blood urea nitrogen when compared with basal levels (P = 0.01 and P = 0.03).

Conclusions: Continuous pressure-controlled NEVKP is feasible and safe in good quality heart-beating donor kidney grafts. It maintains a physiologic environment and excellent graft function ex vivo during preservation without causing graft injury.
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http://dx.doi.org/10.1097/TP.0000000000001299DOI Listing
September 2016

Commentary to 'Continence and quality of life with the modified Heitz-Boyer-Hovelaque rectal bladder for children with urinary incontinence following bladder exstrophy'.

J Pediatr Urol 2016 Jun 31;12(3):175-6. Epub 2016 Mar 31.

Division of Paediatric Urology, The Hospital for Sick Children, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1016/j.jpurol.2016.03.007DOI Listing
June 2016

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

PLoS One 2016 10;11(3):e0149118. Epub 2016 Mar 10.

Faculty of Arts and Sciences, University of Toronto, Toronto, Ontario, Canada.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0149118PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786126PMC
July 2016

Impact of drainage technique on pediatric pyeloplasty: Comparative analysis of externalized uretero-pyelostomy versus double-J internal stents.

Can Urol Assoc J 2015 Jul-Aug;9(7-8):E453-7

Division of Urology, Hospital for Sick Children and Department of Surgery, University of Toronto, Toronto, ON.

Introduction: Pediatric pyeloplasty with double J (DJ) stent drainage requires manipulation of the uretero-vesical junction (UVJ) and a second anesthetic for removal. Externalized uretero-pyelostomy (EUP) stents avoid these issues. We report outcomes of laparoscopic and open pyeloplasty with EUP compared to DJ stents in children.

Methods: We retrospectively reviewed 76 consecutive children who underwent pyeloplasty for ureteropelvic junction (UPJ) obstruction over a 1-year period by 5 pediatric urologists at a single institution. The exclusion criteria included patients with concomitant urological procedures, other urinary drainage strategies, "stentless" pyeloplasty or patients without follow-up data. Based on surgeon preference, 24 patients had a EUP stent and 38 had a DJ stent placed.

Results: The mean follow-up was 23.8 ± 10.9 months and 21.1 ± 11.1 months for the EUP and DJ stent groups, respectively (p = 0.32). The mean age was 40 ± 54 months and 80 ± 78 months for the EUP and DJ groups, respectively (p = 0.04). The EUP group had a greater proportion of open pyeloplasties (n = 17, 71%) versus the DJ group (n = 16, 42%; p = 0.04). There were no statistically significant differences in operative time, length of stay, and overall complication rate between groups. Complications were divided by timing of complication (intraoperative, before and after 3 months) and according to the Clavien Classification system. There were no statistically significant differences between these subgroups. The limitations of this study include small sample size, potential selection bias, and heterogeneity between both study groups.

Conclusions: Pyeloplasty using EUP stents does not incur prolonged operative time, longer length of stay or higher complication rate when compared to DJ stents. Within the limitations of this study, EUP stents may be a safe alternative to DJ stents.
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http://dx.doi.org/10.5489/cuaj.2697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514491PMC
August 2015

Inappropriate Use of Ultrasound in Management of Pediatric Cryptorchidism.

Pediatrics 2015 Sep 10;136(3):479-86. Epub 2015 Aug 10.

Division of Urology, The Hospital for Sick Children and Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada;

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.
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http://dx.doi.org/10.1542/peds.2015-0222DOI Listing
September 2015

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

J Pediatr Surg 2015 Oct 20;50(10):1776-82. Epub 2015 Jun 20.

Division of Urology, The Hospital for Sick Children, Main Floor, Black Wing Room M299, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada; University of Toronto, 563 Spadina Crescent, Toronto, Ontario M5S 2J7, Canada.

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.
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http://dx.doi.org/10.1016/j.jpedsurg.2015.06.005DOI Listing
October 2015

Novel Strategy for Temporary Decompression of the Lower Urinary Tract in Neonates Using a Ureteral Stent.

J Urol 2015 Oct 9;194(4):1086-90. Epub 2015 May 9.

Division of Pediatric Urology, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.

Purpose: In children with congenital obstructive uropathy, including posterior urethral valves, lower urinary tract decompression is recommended pending definitive surgical intervention. Current options, which are limited to a feeding tube or Foley catheter, pose unappreciated constraints in luminal diameter and are associated with potential problems. We assess the impact of luminal diameter on the current draining options and present a novel alternative method, repurposing a widely available stent that optimizes drainage.

Materials And Methods: We retrospectively reviewed patients diagnosed with posterior urethral valves between January 2013 and December 2014. In all patients a 6Fr 12 cm Double-J ureteral stent was advanced over a guidewire in a retrograde fashion into the bladder. Luminal flow and cross-sectional areas were also assessed for each of 3 tubes for urinary drainage, ie 6Fr Double-J stent, 5Fr feeding tube and 6Fr Foley catheter.

Results: A total of 30 patients underwent uneventful bedside Double-J stent placement. Mean ± SD age at valve ablation was 28.5 ± 16.6 days. Mean ± SD peak serum creatinine was 2.23 ± 0.97 mg/dl after birth and 0.56 ± 0.22 mg/dl at the procedure. Urine output after stent placement was excellent in all patients. The Foley catheter and feeding tube drained approximately 18 and 6 times more slowly, respectively, and exhibited half the calculated cross-sectional luminal area compared to the Double-J stent.

Conclusions: Use of Double-J stents in neonates with posterior urethral valves is a safe and effective alternative method for lower urinary tract decompression that optimizes the flow/lumen relationship compared to conventional drainage options.
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http://dx.doi.org/10.1016/j.juro.2015.04.102DOI Listing
October 2015

Impact of penile degloving and proximal ventral dissection on curvature correction in children with proximal hypospadias.

Can Urol Assoc J 2014 Nov;8(11-12):424-7

Division of Urology, The Hospital for Sick Children and University of Toronto, Toronto, ON;

Introduction: Penile degloving is an important step in orthoplasty. Although its role in correcting mild curvature in distal and midshaft hypospadias has been previously reported, its impact on ventral curvature (VC) correction in proximal defects warrants further investigation. Therefore, we sought to document the effect of degloving and proximal urethral dissection on VC correction in children with proximal hypospadias.

Methods: We retrospectively reviewed the records of 137 patients who underwent proximal hypospadias repair between 1998 and 2006. VC, defined as mild (<30%), moderate (30%-45%), and severe (>45%), was recorded before penile degloving and after erection test. Percent improvement in VC and need for further treatment (beyond degloving and proximal dissection) based on preoperative degree of curvature were assessed. ANOVA test was used to compare improvement among the 3 groups.

Results: Mean age at repair was 14 months (range: 6-24). Penile degloving associated with proximal urethral dissection when necessary was responsible for the improvement in the degree of curvature in 7 of 9 (77%) patients with mild VC, 23 of 44 (52%) with moderate and 35 of 84 (40%) with severe VC. Additionally, degloving alone was sufficient for VC correction in 7 of 9 (77%) mild cases, 14 of 44 (30%) moderate and only 2 of 84 (2%) severe cases. The difference among these 3 groups was statistically significant (p < 0.001).

Conclusions: Penile degloving alone can correct VC. The percentage of improvement depends on the preoperative degree of curvature, with severe VC cases showing the least improvement.
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http://dx.doi.org/10.5489/cuaj.2337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277522PMC
November 2014

NOTch just a bladder control problem.

Cancer Cell 2014 Oct;26(4):452-4

Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ccell.2014.09.018DOI Listing
October 2014

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

J Urol 2015 Feb 16;193(2):632-6. Epub 2014 Sep 16.

Division of Urology, Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Pediatric Urology, LeBonheur Children's Hospital, Department of Urology, University of Tennessee, Memphis, Tennessee (JMG).

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.
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http://dx.doi.org/10.1016/j.juro.2014.09.004DOI Listing
February 2015

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

J Urol 2014 May 26;191(5 Suppl):1558-63. Epub 2014 Mar 26.

Divisions of Urology, Hospital for Sick Children and University of Toronto, Toronto and McMaster Children's Hospital and McMaster University (LHPB), Hamilton, Ontario, Canada.

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.
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http://dx.doi.org/10.1016/j.juro.2013.10.036DOI Listing
May 2014

Assessment of local structural disorders of the bladder wall in partial bladder outlet obstruction using polarized light imaging.

Biomed Opt Express 2014 Feb 27;5(2):621-9. Epub 2014 Jan 27.

University of Toronto, Division of Biophysics and Bioimaging, Ontario Cancer Institute/University Health Network and Department of Medical Biophysics, 610 University Avenue, Toronto, Ontario M5G 2M9 Canada ; University of Toronto, Department of Radiation Oncology, 610 University Avenue, Toronto, Ontario M5G 2M9 Canada.

Partial bladder outlet obstruction causes prominent morphological changes in the bladder wall, which leads to bladder dysfunction. In this paper, we demonstrate that polarized light imaging can be used to identify the location of obstruction induced structural changes that other imaging modalities fail to detect. We induced 2-week and 6-week partial outlet obstruction in rats, harvested obstructed bladders, then measured their retardances while distended to high pressures and compared them to controls. Our results show that the retardance of the central part of the ventral side (above the ureters) closer to the urethra can be used as a potential metric of the distending bladder obstruction.
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http://dx.doi.org/10.1364/BOE.5.000621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920890PMC
February 2014

Single center experience with oxybutynin transdermal system (patch) for management of symptoms related to non-neuropathic overactive bladder in children: an attractive, well tolerated alternative form of administration.

J Pediatr Urol 2014 Aug 17;10(4):753-7. Epub 2014 Jan 17.

Division of Urology, The Hospital for Sick Children, Department of Surgery, The University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Electronic address:

Objective: Oxybutynin is the current gold standard drug for management of overactive bladder (OAB) in children, but can have significant side effects or be difficult to administer in multiple daily doses. Herein, we report our experience with transdermal oxybutynin patch (TOP) as an alternative in a selected patient population without neuropathic compromise.

Materials And Methods: Consecutive patients assessed in a pediatric urology clinic over a 1-year period, diagnosed with OAB with minimum follow-up of 3 months, were included. TOP starting dose was 3.9 mg/day based on product design (Oxytrol). Demographics and outcomes data were retrospectively collected. Symptomatic response was defined as improvement or resolution of lower urinary tract symptoms.

Results: 35 children met inclusion criteria (mean age 8 years, range 4-16). Overall, 97% reported good symptom response. The main side effect was skin irritation at TOP site (35%), leading to discontinuation in 20%. There were no reports of other significant side effects. Mean bladder capacity increased from 104 ml to 148 ml at follow-up.

Conclusions: Our data suggest that TOP is a viable alternative for children with non-neuropathic OAB who do not tolerate other formulations of oxybutynin. These findings highlight the potential benefit of transdermal drug delivery in the pediatric setting.
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http://dx.doi.org/10.1016/j.jpurol.2013.12.017DOI Listing
August 2014