Publications by authors named "Walid A Farhat"

131 Publications

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

Chemotherapeutic resistance of head and neck squamous cell carcinoma is mediated by EpCAM induction driven by IL-6/p62 associated Nrf2-antioxidant pathway activation.

Cell Death Dis 2020 08 20;11(8):663. Epub 2020 Aug 20.

Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines. We report that EpCAM was highly expressed in Nrf2-positive and HPV-negative HNSCC cells. In addition, cisplatin-resistant tumor cells consisted of a higher proportion of EpCAM cells compared to the cisplatin sensitive counterpart. EpCAM populations exhibited resistance to cisplatin, a higher efficiency in colony formation, sphere growth and invasion capacity, and demonstrated reduced reactive oxygen species (ROS) activity. Furthermore, Nrf2 expression was significantly higher in EpCAM populations. Mechanistically, expression of Nrf2 and its target genes were most prominently observed in EpCAM populations. Silencing of EpCAM expression resulted in the attenuation of expressions of Nrf2 and SOD1 concomitant with a reduction of Sox2 expression. On the other hand, silencing of Nrf2 expression rendered EpCAM populations sensitive to cisplatin treatment accompanied by the inhibition of colony formation, sphere formation, and invasion efficiency and increased ROS activity. The molecular mechanistic link between EpCAM expression and activation of Nrf2 was found to be a concerted interaction of interleukin-6 (IL-6) and p62. Silencing of p62 expression in EpCAM populations resulted in the attenuation of Nrf2 pathway activation suggesting that Nrf2 pathway activation promoted resistance to cisplatin in EpCAM populations. We propose that therapeutic targeting the Nrf2-EpCAM axis might be an excellent approach to modulate stress resistance and thereby survival of HNSCC patients enriched in EpCAM populations.
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http://dx.doi.org/10.1038/s41419-020-02907-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438524PMC
August 2020

Comparative outcome analysis of pediatric kidney transplant in posterior urethral valves children with or without pretransplant Mitrofanoff procedure.

Pediatr Transplant 2020 12 2;24(8):e13798. Epub 2020 Aug 2.

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

Background: Urinary diversion using catheterizable channel among posterior urethral valve (PUV) patients may help to alleviate the functional concerns of the bladder on the allograft. Herein, we review our series of PUV patients undergoing renal transplants at a single institution to determine outcomes between those with and without pretransplant Mitrofanoff.

Methods: PUV cases in our transplant database from 2000 to 2017 were identified. Data collected included clinical demographics, presentation of PUV, bladder function, implementation of dialysis and donor type. Post-transplant variables included graft function, and bladder function including incontinence and UTI development. Comparison between with vs without pretransplant Mitrofanoff patient groups was performed using Fisher's exact and t test analysis.

Results: Overall, 22 cases were analyzed. The majority (77%) had a prenatal diagnosis of PUV, and 23% had a symptomatic presentation. Pretransplant Mitrofanoffs were performed in 40.9% of cases. The overall age at transplant was 10 ± 5 years. Five percent experienced post-transplant incontinence and 23% UTIs. No difference between groups was noted in variables including age at transplant, the timing of PUV diagnosis. Mitrofanoff group patients had more symptomatic febrile UTIs than those without Mitrofanoff (67% vs 15%; P = .03); however, there was no difference in post-transplant UTI development. Furthermore, the Mitrofanoff group seems to have later onset of dialysis or need for transplant (age at the start of dialysis 36 ± 56 vs 156 ± 25 months, P < .001).

Conclusion: Our study suggests that patients with early PUV diagnoses who develop symptomatic UTI may benefit from early creation of a Mitrofanoff cathetherizable channel, which is associated with delayed ESRD progression and need for dialysis.
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http://dx.doi.org/10.1111/petr.13798DOI Listing
December 2020

Competency in Tubularized Incised Plate Repair for Distal Hypospadias: Cumulative Sum Learning Curve Analysis of a Single Surgeon Experience.

J Urol 2020 Dec 2;204(6):1326-1332. Epub 2020 Jul 2.

Division of Pediatric Urology, Department of Urology, University of Wisconsin, Madison, Wisconsin.

Purpose: We sought to determine the number of cases to achieve competency and proficiency in tubularized incised plate technique for distal hypospadias repair using cumulative sum analysis.

Materials And Methods: From 2001 to 2015 we reviewed all distal tubularized incised plate repairs performed by a single surgeon since independent practice. Data for 450 consecutive cases included age, meatal location, presence of curvature, operative time, occurrence of complications and followup duration. A cumulative sum analysis cohort chart was used to determine trends in complication rate and operative time during the evaluation period. In order to account for surgical experience with time, the highest peak, plateau, and down trends in operative time and complication rate were identified on the plot and set as the transition points between learning (phase 1), competence (phase 2) and proficiency (phase 3).

Results: Based on the cumulative sum analysis learning curve, the competence phase with plateau of operative time and complication rate commences beyond the 127th case, and the proficiency phase with notable decline in operative time and complication rate was noted beyond the 234th case. When comparing case characteristics and surgical outcomes between phases and learning curve, the proficiency phase involved younger patients and more severe degree of distal hypospadias being repaired using the tubularized incised plate approach with fewer complications related to meatal stenosis and fewer cosmetic complications.

Conclusions: In our study competency in distal hypospadias tubularized incised plate repair was reached beyond the 127th case, while proficiency was attained beyond the 234th case.
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http://dx.doi.org/10.1097/JU.0000000000001231DOI Listing
December 2020

Pediatric Kidney Transplant Experience in Ontario: A Review of Division of the Surgical and Medical Management Across Local Tertiary Care Institutions.

Can J Kidney Health Dis 2020 8;7:2054358120925712. Epub 2020 Jun 8.

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

Background: Our institution is the largest pediatric kidney transplantation (KT) center in Canada and the referral center for pediatric KT in Ontario. Pediatric KT recipients are referred to our center for KT and transferred back to their local tertiary care institutions for post-transplant care. This investigation assesses whether the current system of transferring patients back to their local tertiary care institutions following KT allows decreased burden and distribution of resources from a single centralized surgical center.

Methods: A retrospective review of KT performed at our institution between 2000 and 2015 was performed. Patients were divided into those who began their chronic kidney disease (CKD) care at our institution and those who began their care elsewhere. Readmission to our institution within 1 year of KT for surgical and nonsurgical complications was compared. The geographical proximity of patients to our institution and institution of initial CKD care was assessed quantitatively and mapped visually.

Results: Of 324 patients who underwent KT, 244 (75.3%) began their CKD care at our institution. Those who began their CKD care at other institutions had shorter initial admissions to our institution (17 [14-24] vs 14 [12-17], < .0001) and were less likely to be readmitted to our institution for nonsurgical concerns at <6 months after transplant ( < .0001) and 6 to 12 months after transplant ( < .0001). There were similar readmissions for complications requiring surgical management. The relationship between the center of CKD initiation and readmission remained significant on multivariate analysis. There was a significant difference in distance (km) to our institution between the 2 groups (46 [interquartile range = 24-109] vs 203 [117-406], < .0001).

Conclusion: Patients who are geographically distanced from our institution began their CKD care at their closest institution and were managed effectively at those institutions following initial discharge/transfer of care, suggesting that there is an effective distribution of health care resources with regard to CKD and KT care.
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http://dx.doi.org/10.1177/2054358120925712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285935PMC
June 2020

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

Widespread expression of Sonic hedgehog (Shh) and Nrf2 in patients treated with cisplatin predicts outcome in resected tumors and are potential therapeutic targets for HPV-negative head and neck cancer.

Ther Adv Med Oncol 2020 13;12:1758835920911229. Epub 2020 Mar 13.

Department of Molecular Oncology, Cancer Biology and Experimental Therapeutics, King Faisal Specialist Hospital and Research Centre, School of Medicine, Alfaisal University, Thakassussi Street, Riyadh, 11211, Saudi Arabia.

Background: Sonic hedgehog (Shh) and Nrf2 play a critical role in chemotherapeutic resistance. These two genes have been found to be dysregulated in head and neck squamous cell carcinomas (HNSCC). The purpose of this study was to analyze the expression, function and clinical prognostic relationship of Shh and Nrf2 in HNSCC in the context of therapeutic resistance and cancer stem cells (CSCs).

Methods: We analyzed a cohort of patients with HNSCC to identify potential therapeutic biomarkers correlating with overall survival (OS) as well as disease-free survival (DFS) from our own data and validated these results using The Cancer Genome Atlas dataset. Expression of Shh and Nrf2 was knocked down by siRNA and cell growth, sphere growth and chemotherapeutic resistance were evaluated.

Results: Widespread abundant expression of Shh and Nrf2 proteins were associated with shorter OS and DFS. The combination of Shh and Nrf2 expression levels was found to be a significant predictor of patient DFS. The tumor stromal index was correlated with Shh expression and inversely associated with shorter OS and DFS. Inhibition of Shh by siRNA or cyclopamine resulted in the attenuation of resistant CSC self-renewal, invasion, clonogenic growth and re-sensitization to the chemotherapeutic agents. Concomitant upregulation of Shh and Nrf2 proved to be an independent predictor of poor OS and DFS in patients with HNSCC.

Conclusions: These findings suggest that Shh and Nrf2 could serve as therapeutic targets as well as promising dual prognostic therapeutic biomarkers for HNSCC.
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http://dx.doi.org/10.1177/1758835920911229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074584PMC
March 2020

Increased hand digit length ratio (2D:4D) is associated with increased severity of hypospadias in pre-pubertal boys.

Pediatr Surg Int 2020 Feb 20;36(2):247-253. Epub 2019 Nov 20.

Division of Urology, The Hospital for Sick Children, Toronto, ON, M5G1X8, Canada.

Introduction: Hypospadias is a common congenital male disorder, with much research focusing on prenatal androgen exposure as a causative factor. Whilst digit length ratios were apparent in sexual dimorphism since the nineteenth century, their role in hypospadias remains unknown. The objective of our study was to determine the correlation between digit length (2D:4D) ratio, hypospadias severity, and anogenital distance.

Methods: Pre-pubertal boys (<3 years old) seen intra/postoperatively following hypospadias repair (June 2018-January 2019 inc.) were included. These were age-matched to non-hypospadias controls. Anthropomorphic measurements of digit lengths, penile/glans width, and anogenital distance were measured using digital calipers.

Results: Data measurements were collected for 105 boys with hypospadias (60 distal; 45 proximal) and 55 controls. There were significant differences in 2D:4D ratios in each hand (p < 0.001), as well as individual digits (p < 0.001), and a reduced anogenital distance (p < 0.001), when comparing the proximal group with distal or control groups. There were no significant differences in glans width, or between term- and preterm births.

Conclusions: This study is the first to demonstrate increased 2D:4D ratios with proximal hypospadias, which also correlate with a shortened anogenital distance. This may provide a non-invasive, potentially antenatal, anthropomorphic measurement, as an indirect indicator of aberrant urogenital development.
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http://dx.doi.org/10.1007/s00383-019-04600-3DOI Listing
February 2020

The impact of sex hormones on genital wound healing in mice: a comparative study.

J Pediatr Urol 2019 Dec 18;15(6):635-641. Epub 2019 Sep 18.

Division of Urology, University of Wisconsin, Madison, WI, USA; Division of Urology, The Hospital for Sick Children, Toronto, ON, Canada.

Introduction And Objective: The effects estrogen and testosterone have on penile wound healing are still uncertain. This study evaluated the effects of these hormones on the wound healing process of penile and non-penile skin in wild-type (Mus musculus species) 4-5-week-old mice.

Methodology: Seventy wild-type Mus musculus species were randomly assigned to four groups control (n = 17), 1-week post-operative topical estrogen (n = 18), 1-week pre-operative testosterone (n = 17), and immediate post-operative testosterone (n = 18). Incisions were made on the ventrum of the penis and dorsal neck skin. On post-operative day 3, 7, and 14, incision sites were harvested. Evaluation was performed grossly for postsurgical penile edema and histologically for inflammatory cell concentration, presence of fibrinopurulent materials and distribution of collagen-fibroblastic cells. Each treatment group was compared at the three post-operative time points using the Fisher-Freeman--Halton exact test. CD34 and androgen receptor immunohistostaining was performed for between-group differences to assess microvascular density or vasodilatation and androgen receptor upregulation.

Results: In this study, the experiment noted significant penile edema on post-operative day 7 in the testosterone groups, whereas less edema in the estrogen group (P = 0.010; Figure). On histologic evaluation of the penile wounds, a significantly increased inflammatory cell concentration was noted for both pre-operative and post-operative testosterone groups on post-operative day 14 (P = 0.023). The estrogen group revealed significantly increased fibrinopurulent material on the 3rd and 7th post-operative days (P = 0.045 and P = 0.005, respectively). No significant between-group differences in the collagen-fibroblastic distribution were noted over the three-time phases. On histologic evaluation of the skin wounds, no significant differences were noted between the groups for inflammatory cell concentration and presence of fibrinopurulent materials. However, compared with the testosterone treatment groups, a significant higher collagen-fibroblast distribution was noted in the estrogen groups on post-operative day 3 and 14 (P = 0.001 and P = 0.044, respectively).

Conclusion: Sex hormones, when given peri-operatively, may affect the wound healing process in mice. Testosterone appears to stimulate a prolonged inflammatory effect on penile wounds. Conversely, estrogen induces a fibrinopurulent congregation early in the penile wound healing process. For general skin healing, estrogen induces earlier collagen and fibroblast distribution, whereas testosterone has a delayed effect. The findings of this study should be further investigated in larger animal model with longer follow-up period.
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http://dx.doi.org/10.1016/j.jpurol.2019.09.001DOI Listing
December 2019

Impact of previous abdominal surgery on the outcome of laparoscopy-assisted open appendicovesicostomy (Mitrofanoff) creation in children: a comparative study.

J Pediatr Urol 2019 Dec 9;15(6):662.e1-662.e7. Epub 2019 Sep 9.

Division of Urology, The Hospital for Sick Children, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada.

Introduction And Objective: For patients who require self-intermittent catheterization, a continent catheterizable stoma is a viable option. This patient population often has had previous abdominal surgery (PAS), a risk factor for complicated laparoscopic procedures. Therefore, the authors aim to determine whether PAS has an impact on the peri-operative outcomes of the laparoscopic-assisted Mitrofanoff procedure in children.

Materials And Methods: A research ethics board-approved retrospective review was performed to assess peri-operative outcomes among pediatric patients who underwent laparoscopic-assisted Mitrofanoff procedures in the authors institution from May 2000 to March 2016. Patients with no PAS were compared with those with intraperitoneal PAS. Demographic/baseline characteristics and peri-operative outcomes such as operative time, estimated blood loss, hospital stay, unanticipated additional operations, stomal stenosis, and urinary continence were compared. To ensure there is no confounding based on PAS characteristics, subgroups were created to compare the recency (PAS <1 year ago) and extent (ventriculoperitoneal (VP) shunt vs non-VP shunt PAS) to assess their peri-operative outcomes. Fisher's exact test and Mann-Whitney U test were used to determine statistical significance.

Results: Thirty-four patients (15 no PAS and 19 PAS) were included in the analysis. No significant difference in demographics and baseline characteristics was noted between the patient groups. The median age was 6.5 years (interquartile range [IQR] 4.8-14.0) and 9.9 years (4.2-14.3), respectively (NS). Peri-operative outcomes of operative time, estimated blood loss, and hospital stay were similar between the PAS and no PAS groups. There was no statistical difference in complications requiring surgical intervention (n = 3, 20.0%; n = 9, 47.4%). The median follow-up period was 25.9 (IQR 7.7-47.2) months and 28.0 (IQR 13.0-53.0) months, respectively (NS). Patients with VP shunts as their only PAS had higher estimated blood loss compared with no PAS group (50 [IQR 25-150], 25 [IQR 25-50], respectively) but without other differences in peri-operative outcomes.

Discussion: Findings support the use of a minimally invasive approach in this patient population as it is feasible, comparable, and safe but with careful consideration for risk factors that may predispose PAS patients to postsurgical complications requiring intervention. Although limited by small sample size, this study provides valuable insight into performing laparoscopic operations in children who have undergone prior surgeries and invites future studies to compare the outcomes between patients undergoing open, pure laparoscopic, and robotic-assisted laparoscopic Mitrofanoff procedures for children with PAS.

Conclusion: Laparoscopic-assisted Mitrofanoff creation may be safely performed in children with PAS.
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http://dx.doi.org/10.1016/j.jpurol.2019.09.003DOI Listing
December 2019

Review of clinical experience on biomaterials and tissue engineering of urinary bladder.

World J Urol 2020 Sep 20;38(9):2081-2093. Epub 2019 Jun 20.

Eastern Virginia Medical School, Norfolk, VA, USA.

Purpose: In recent pre-clinical studies, biomaterials and bladder tissue engineering have shown promising outcomes when addressing the need for bladder tissue replacement. To date, multiple clinical experiences have been reported. Herein, we aim to review and summarize the reported clinical experience of biomaterial usage and tissue engineering of the urinary bladder.

Methods: A systematic literature search was performed on Feb 2019 to identify clinical reports on biomaterials for urinary bladder replacement or augmentation and clinical experiences with bladder tissue engineering. We identified and reviewed human studies using biomaterials and tissue-engineered bladder as bladder substitutes or augmentation implants. The studies were then summarized for each respective procedure indication, technique, follow-up period, outcome, and important findings of the studies.

Results: An extensive literature search identified 25 studies of case reports and case series with a cumulative clinical experience of 222 patients. Various biomaterials and tissue-engineered bladder were used, including plastic/polyethylene mold, preserved dog bladder, gelatine sponge, Japanese paper with Nobecutane, lypholized human dura, bovine pericardium, amniotic membrane, small intestinal mucosa, and bladder tissue engineering with autologous cell-seeded biodegradable scaffolds. However, overall clinical experiences including the outcomes and safety reports were not satisfactory enough to replace enterocystoplasty.

Conclusion: To date, several clinical experiences of biomaterials and tissue-engineered bladder have been reported; however, various studies have reported non-satisfactory outcomes. Further technological advancements and a better understanding is needed to advance bladder tissue engineering as a future promising management option for patients requiring bladder drainage.
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http://dx.doi.org/10.1007/s00345-019-02833-4DOI Listing
September 2020

Assessment of prophylactic heparin infusion as a safe preventative measure for thrombotic complications in pediatric kidney transplant recipients weighing <20 kg.

Pediatr Transplant 2019 09 6;23(6):e13512. Epub 2019 Jun 6.

Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Small-sized kidney recipients (<20 kg) are at high risk of allograft vessel thrombosis. HP has been used to mitigate this risk but may infer an increase in bleeding risks. Therefore, we aim to determine whether HP is a safe means to prevent thrombosis in small kidney transplant patients by comparing those who have received HP and those who have NHP. A retrospective review of patients < 20 kg who underwent kidney transplant in our institution from 2000 to 2015 was performed. At our institution, unfractionated heparin 10 units/kg/hour is used as HP since 2009. Patients at increased risk of thrombosis (previous thrombosis, thrombophilia, nephrotic syndrome) and bleeding (therapeutic doses of heparin, diagnosis of coagulopathy) were excluded. Fifty-six patients were identified (HP n = 46; NHP n = 10). Baseline demographics were similar between HP and NHP. There was no statistical difference in frequency of transfusions, surgical re-exploration, or thrombotic events between HP and NHP. The HP group was more likely to have drop in Hb > 20 g/L (67.4% vs 30.0%, P = 0.038), and those who had drop in Hb > 20 g/L were more likely to also require pRBC transfusions (63.0% vs 20.0%, P = 0.017). Within the HP group, those who had bleeding complications had similar Hb levels as those who did not at baseline and post-transplant. Outcomes in the HP and NHP groups were no different with respect to thrombosis or significant bleeding complications requiring pRBC transfusions or surgical intervention. Future prospective studies are required to investigate the balance of preventing thrombosis and risks of pRBC transfusions for small-sized kidney recipients.
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http://dx.doi.org/10.1111/petr.13512DOI Listing
September 2019

Antibody-drug conjugate T-DM1 treatment for HER2+ breast cancer induces ROR1 and confers resistance through activation of Hippo transcriptional coactivator YAP1.

EBioMedicine 2019 May 10;43:211-224. Epub 2019 May 10.

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

Background: A newly developed drug trastuzumab emtansine (T-DM1) has improved the survival of breast cancer (BC) patients. Despite an impressive initial clinical response, a subgroup of patient develop resistance and present therapeutic challenges. The underlying resistance mechanisms are not fully investigated. We report that T-DM1 treatment modulates the expression of ROR1 (type 1 receptor tyrosine kinase-like orphan receptor) and induces self-renewal of cancer stem cells (CSCs) leading to therapeutic resistance.

Methods: Using BC patient tumor samples, and BC cell lines we gained insight into the T-DM1 treatment induced ROR1 overexpression and resistance. In vitro sphere forming assays and in vivo extreme dilution assays were employed to analyze the stemness and self-renewal capacity of the cells. A series of molecular expression and protein assays including qRT-PCR, FACS-sorting, ELISA, immunostaining, Western blotting were used to provide evidence.

Findings: Exposure of cells to T-DM1 shifted ROR1 expression from low to high, enriched within the CSC subpopulation, coincident with increased Bmi1 and stemness factors. T-DM1 induced ROR1 cells showed high spheroid and tumor forming efficiency in vitro and in an animal model exhibiting shorter tumor-free time. Mechanistically, the overexpression of ROR1 is partly induced by the activation of YAP1 and its target genes. Silencing of ROR1 and YAP1 by pharmacologic inhibitors and/or sh/siRNA inhibited spheroid formation, the initiation of tumors and the capacity for self-renewal and ROR1 overexpression.

Interpretations: The results presented here indicate that simultaneous targeting of ROR1 and YAP1 may suppress CSC self-renewal efficacy and inhibit tumor progression in BC. In this manner such treatments may overcome the T-DM1 mediated therapeutic resistance and improve clinical outcome. FUND: This study was supported by Neurogen Technologies for interdisciplinary research.
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http://dx.doi.org/10.1016/j.ebiom.2019.04.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558306PMC
May 2019

Is there a functional disadvantage to using the external iliac vessels for vascular anastomosis in children and adolescents undergoing renal transplantation?

Pediatr Transplant 2019 06 27;23(4):e13398. Epub 2019 Mar 27.

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

Purpose: RT remains the best available strategy for addressing stage 5 chronic kidney disease in children and adolescents. Technical aspects of the procedure can have a clear impact on complications and health of the allograft, including DGF. Immediate optimal perfusion is paramount, thus choosing a target vessel has to take into account the flow demands imposed by an adult-size kidney in a proportionally smaller recipient. Herein, we explore the hypothesis that vascular anastomosis location can impact DGF adjusting for patient age and body size.

Methods: Retrospective review of a single institution referral center transplant database, including information on 156 patients. We collected data on patient characteristics (age, height, BSA, gender, preoperative need for dialysis), donor source (deceased vs living), WIT/CIT, hemodynamics during the procedure, use of inotropes or diuretics, and location of the arterial and venous anastomoses. The primary outcome, DGF, was assessed by measuring the ttNC (in days), adjusting for age and BSA.

Results: Location of the arterial anastomosis was clearly impacted by age and donor size (Figure 1A). On univariate analyses, longer ttNC was associated with deceased vs living donor (11.8 ± 11.5 and 4.3 ± 5.0; P < 0.001), preoperative need for dialysis (9.7 ± 11.0 and 6.5 ± 6.0, P = 0.02), location of arterial anastomosis (aorta [n = 21] 4.9 ± 6.1, common iliac [n = 93] 7.1 ± 7.3, external iliac 14.7 ± 14.5; P < 0.001, Figure 1B) and venous anastomosis (vena cava [n = 21] 5.6 ± 6.3, common iliac [n = 89] 7.1 ± 7.6, external iliac [n = 44] 13.8 ± 14); P < 0.001). On multivariable analysis, this association remained statistically significant when adjusting for recipient age, height, BSA, donor source, change in blood pressure with unclamping, and use of inotropes and preoperative dialysis. The detrimental effect on ttNC was more salient when comparing external iliac vs common iliac and aorta or vena cava.

Conclusion: Our data suggest that anastomosis to a smaller caliber target vessel (ie, external iliac) in comparison with the common iliac or aorta/vena cava may be a risk factor for delayed return of graft function, independent of recipient size and donor source. This finding merit further evaluation, as it may help with intraoperative decision making during pediatric and adolescent RT.
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http://dx.doi.org/10.1111/petr.13398DOI Listing
June 2019

A Comprehensive Analysis of Robot-Assisted Surgery Uptake in the Pediatric Surgical Discipline.

Front Surg 2019 12;6. Epub 2019 Mar 12.

Division of Urology, Hospital for SickKids, University of Toronto, Toronto, ON, Canada.

Robotic assisted surgery (RAS) is one of the most recent surgical approaches that has quickly been adopted by the pediatric urology community. Over the last decade, a vast amount of manuscripts has been published, supporting the safety and applicability of RAS in the pediatric population. The quality of published literature about this innovative technology remains supported by case-reports and retrospective case-series. Historical behavior of literature productivity and implementation of laparoscopy followed a similar trend. We present the historical publication uptake of RAS in pediatric urology and other surgical disciplines using a bibliometric comparison of the most cited manuscripts. A systematic search and review of the literature was undertaken by the authors. Literature search was performed in OVID, PubMed, EMBASE, Scopus, Web of Science, and Google Scholar. The search period included all publications between 1985 and June 2018. All languages were included. Data analysis for graphical representation was performed using VOSviewer version 1.6.8 and Impact Index Analysis was used to adjust the citations by the time since publication. A total of 1,014 titles were identified. After applying exclusion criteria, 200 papers were included for the RAS arm and 402 for the laparoscopic one. Case-series was the most common type of publication. Average citations for laparoscopic manuscripts was 23 ( ± 31) and for RAS was 20 ( ± 31.5). The impact index analysis showed an average of 95 ( ± 167) for laparoscopic manuscripts vs. 66 ( ± 101) for RAS. The laparoscopic manuscript with the highest citation count had 199 citations with an impact index of 12.1. And the RAS manuscript with the highest citation count had 280 citations and an impact index of 4.3. Literature productivity in pediatric laparoscopic and RAS has quickly grown. Pediatric Urologists play a key role in the introduction of this innovative tool. Literature supporting its implementation and future consolidation requires to focus on increasing the level of evidence.
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http://dx.doi.org/10.3389/fsurg.2019.00009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422870PMC
March 2019

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

Can J Surg 2019 Mar 22;62(3):1-6. Epub 2019 Mar 22.

From the Faculty of Medicine, University of Toronto, Toronto, Ont. (Kim, Lee); the Division of Urology, The Hospital for Sick Children, Toronto, Ont. (Kim, Chua, Ming, Lee, Kesavan, Kahn, Lorenzo, Bagli, Farhat, Papanikolaou, Koyle); the School of Medicine, Royal College of Surgeons in Ireland, Dublin, Republic of Ireland (Kesavan); the Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Ont., (Langer); and the Department of Surgery, University of Toronto, Toronto, Ont. (Langer, Lorenzo, Bagli, Farhat, Papanikolaou, Koyle).

Background: Before 2014, there was a lack of recommendations on managing cryptorchidism, or undescended testis (UDT), from a large pediatric urological or surgical organization. We assessed the variability in management of UDT among pediatric urologists and pediatric surgeons at a single tertiary pediatric referral centre before publication of major guidelines.

Methods: We performed a retrospective review of the electronic records of patients who underwent primary unilateral or bilateral orchidopexy at our centre between January 2012 and January 2014.

Results: A total of 488 patients (616 testes) were identified, of whom 405 (83.0%) and 83 (17.0%) were managed by pediatric urologists and pediatric surgeons, respectively. There was no difference in baseline characteristics, including age seen in clinic or at surgery, testis location/palpability and availability of preoperative ultrasonograms, of patients seen by the 2 groups. Pediatric surgeons ordered preoperative ultrasonography more often than pediatric urologists (25.3% v. 3.7%, p < 0.001). With palpable UDTs, although both groups used open approaches, pediatric urologists preferred a scrotal approach (56.9%), and pediatric surgeons approached most testes inguinally (98.8%). With nonpalpable UDTs, laparoscopic approaches were preferred by both groups; however, pediatric urologists used a 2-stage Fowler–Stephens approach more often than pediatric surgeons (48.4% v. 15.8%, p < 0.001).

Conclusion: There was wide variation in the management of primary UDT between pediatric urologists and pediatric surgeons before the publication of guidelines. The most prominent difference between the 2 groups was in the ordering of preoperative ultrasonography. Future assessment of change in practice patterns may elucidate whether guidelines are an effective tool for standardization of practice.
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http://dx.doi.org/10.1503/cjs.014017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738503PMC
March 2019

A comparison of post-transplant renal function in pre-emptive and post-dialysis pediatric kidney transplant recipients.

Pediatr Transplant 2019 05 8;23(3):e13377. Epub 2019 Feb 8.

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

Purpose: Little is known regarding post-transplant renal function following pediatric pre-emptive KT. Therefore, this study aims to determine whether there is a difference in 1 year post-transplant renal function outcomes between pre-emptive and post-dialysis KT in pediatric transplant recipients.

Methods: A retrospective review of patients who underwent kidney transplant at our institution between 2000 and 2015 was performed. Kidney transplant recipients were divided into four groups: pre-DD, post-DD, pre-LD, and post-LD. The clinical outcomes, measured in eGFR (mL/min/1.73 m ), acute rejection episodes within 1 year, and hospitalization within 1 year were compared to between groups in their respective donor types (pre-DD vs post-DD; pre-LD vs post-LD).

Results: The 324 patients were identified (21 pre-DD, 151 post-DD, 54 pre-LD, and 98 post-LD). Post-DD group had more females (P = 0.018) and post-operative complications (P = 0.023), although there was no difference in complications requiring intervention (P = 0.129). Post-LD patients were more likely to be females (P = 0.017) and those with intrinsic renal (non-urological/structural) ESRD etiology (P = 0.003). The 1-year eGFR was similar between pre-DD and post-DD groups (70.3 [IQR 53.5-88.5] vs 74.3 [IQR 62.3-90.5], P = 0.613), as well as pre-LD and post-LD groups (66.6 [IQR 47.8-73.7] vs 63.9 [IQR 55.0-77.1], P = 0.600). There were no significant differences in rates of acute rejection episodes or hospitalization within 1 year of transplantation for in LD/DD groups.

Conclusion: There is no significant difference in renal function at 1 year post-transplant in pediatric patients receiving pre-emptive or post-dialysis kidney transplants.
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http://dx.doi.org/10.1111/petr.13377DOI Listing
May 2019

Competence in and Learning Curve for Pediatric Renal Transplant Using Cumulative Sum Analyses.

J Urol 2019 06;201(6):1199-1205

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

Purpose: We assessed achievement of competence in pediatric renal transplant by developing a learning curve model for consecutive operations performed by a single surgeon.

Materials And Methods: We retrospectively evaluated pediatric renal transplant cases performed by an index pediatric urologist during his first 15 years of being the primary transplant surgeon at our institution. Case characteristics, operative time and surgical complications within 30 days postoperatively were assessed and compared to those of a reference senior surgeon. To generate a learning curve plot, we performed a cumulative sum analysis to evaluate the evolution of operative times and surgical complications.

Results: During 15 years 55 pediatric renal transplants (17%) were performed by the index surgeon and 78 (24%) by the senior surgeon. Total operative time was shorter for the index surgeon (226 vs 252 minutes, p = 0.006), while ischemia time was longer (40 vs 30 minutes, p = 0.001). The 30-day surgical complication rates were similar (32.7% and 35.9%, p = 0.853). The learning curve showed that the complication rates and operative times did not increase following the 17th case. Ureteroureterostomy has been more commonly performed for ureteral anastomosis (p = 0.048) and longer warm ischemia time has been noted after reaching the peak of the learning curve (p = 0.003).

Conclusions: We determined that technical skills for pediatric renal transplant can be achieved after the 17th case. We propose that a dedicated team with a pediatric urologist who has an interest in performing pediatric renal transplant secure more cases than the case volume determined in our study within the first few years of practice to maintain proficiency.
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http://dx.doi.org/10.1097/JU.0000000000000021DOI Listing
June 2019

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

J Pediatr Surg 2019 Sep 29;54(9):1820-1824. Epub 2018 Oct 29.

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

Background: This investigation aims to assess the variability in practice patterns regarding management of children with cryptorchidism (UDT) among pediatric urologists (U) and pediatric surgeons (S) practicing in Canada.

Methods: All active members of Pediatric Urologists of Canada (PUC) and Canadian Association of Pediatric Surgery (CAPS) were invited to participate in an online multiple-choice type questionnaire with clinical scenarios in management of UDT. Responses were compared between U and S using Fisher's exact test.

Results: The response rates were 74% and 79% among CAPS members (54/73) and PUC members (27/34) respectively. CAPS members were more likely to order diagnostic ultrasounds prior to surgery (44.4% vs 18.5%, p = 0.027). For palpable testis, most (80%) CAPS members favored the classic inguinal approach, while most PUC members did not demonstrate a clear preference, and were flexible with their approach depending on the position of the palpated testes (55%; p < 0.001). There was no statistically significant difference in preferred approach to unilateral or bilateral nonpalpable testis. However, for both palpable and nonpalpable bilateral UDT, more CAPS members preferred metachronous correction, compared to PUC members who opted to approach them synchronously (p = 0.008, 0.002, respectively).

Conclusion: Preferences with regard to use of diagnostic tools such as US, surgical approach for palpable testes and bilateral UDTs were not consistent between the two surgical specialties who perform orchidopexy across Canada. Both groups were compliant with guideline recommendations, with the exception of utilizing preoperative ultrasounds, which is uniformly not recommended by the most recent guidelines.

Level Of Evidence: This is a level II evidence study.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.10.053DOI Listing
September 2019

Clinical implication of renal allograft volume to recipient body surface area ratio in pediatric renal transplant.

Pediatr Transplant 2018 12 12;22(8):e13295. Epub 2018 Oct 12.

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

Our study aims to assess the clinical implication of RAV/rBSA ratio in PRT as a predictor for attained renal function at 1 year post-transplantation and its association with surgical complications. A retrospective cohort was performed for PRT cases from January 2000 to December 2015 in our institution. Extracted clinical information includes the recipient's demographics, donor type, renal allograft characteristics, arterial, venous and ureteral anastomoses, vascular anastomosis time while kidney off ice, overall operative time, and estimated blood loss. The RAV/rBSA was extrapolated and assessed for its association with renal graft function attained in 1 year post-transplantation and surgical complications within 30-day post-transplantation. A total of 324 PRTs cases were analyzed. The cohort consisted of 187 (52.4%) male and 137 (42.3%) female recipients, with 152 (46.9%) living donor and 172 (53.1%) deceased donor renal transplants, and an overall median age of 155.26 months (IQR 76.70-186.98) at time of renal transplantation. The receiver operating characteristic identified that a RAV/rBSA ratio of 135 was the optimal cutoff in determining the renal graft function outcome. Univariate and multivariate analyses revealed the relative OR for RAV/rBSA ≥ 135 ratio in predicting an eGFR ≥ 90 attained within 1 year post-transplant was highest among younger pediatric recipients (<142.5 months) of deceased kidney donors (OR = 11.143, 95% CI = 3.156-39.34). Conversely, Kaplan-Meier analysis revealed that RAV/rBSA ratio ≥ 135 is associated with lower odds of having eGFR <60 (OR = 0.417, 95% CI = 0.203-0.856). The RAV/rBSA ratio was not associated nor predictive of transplant-related surgical complications. Our study determined that the RAV/rBSA ratio is predictive of renal graft function at 1-year PRT, but not associated with any increased surgical complications.
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http://dx.doi.org/10.1111/petr.13295DOI Listing
December 2018

Assessment of perioperative surgical complications in pediatric kidney transplantation: A comparison of pre-emptive and post-dialysis recipients.

Clin Transplant 2018 12 26;32(12):e13421. Epub 2018 Oct 26.

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

Purpose: To determine whether there is a benefit to pre-emptive kidney transplantation in reducing surgical complications in pediatric population.

Methods: A retrospective review of kidney transplantations in our institution from 2000 to 2015 was performed. Intra- and postoperative complication rates and one-year graft survival were compared in their respective donor type groups (pre-emptive DD vs post-dialysis DD; pre-emptive LD vs post-dialysis LD).

Results: A total of 318 patients were identified (pre-emptive DD, n = 21; post-dialysis DD, n = 145; pre-emptive LD, n = 54; post-dialysis LD, n = 98). Between the DD groups, post-dialysis DD group was more likely to be female (P = 0.017). There was no difference in rates of intraoperative complications or graft loss (P = 0.365 and 1.000, respectively). Post-dialysis DD groups were more likely to have postoperative complications (9.5% vs 35.1%, P = 0.023), but no difference in complications with Clavien-Dindo grade 3 or higher was found (P = 0.130). Between the LD groups, post-dialysis LD group was more likely to be females (P = 0.017) and with intrinsic renal (non-urological/structural) ESRD etiology (P = 0.003). There was no difference in rates of intra-and postoperative complications or graft loss (P = 0.353, P = 0.605, and P = 0.616, respectively).

Conclusions: Overall, there are similar perioperative complication rates between pediatric pre-emptive and post-dialysis kidney transplant recipients.
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http://dx.doi.org/10.1111/ctr.13421DOI Listing
December 2018

Case - Utility of magnetic resonance urography in pediatric urinary incontinence: Radiological considerations.

Can Urol Assoc J 2018 Jul 19;12(7):E357-E359. Epub 2018 Mar 19.

Hospital for Sick Children, Toronto, ON, Canada.

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http://dx.doi.org/10.5489/cuaj.4936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118050PMC
July 2018

Intraoperative blood transfusion in pediatric patients undergoing renal transplant-Effect of renal graft size.

Pediatr Transplant 2018 05 27;22(3):e13119. Epub 2018 Feb 27.

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

In pediatric RT, donor allograft size often exceeds the expected recipient norms, especially in younger recipients. An "oversize" graft might not only present a technical- and space-related challenge, but may possibly lead to increased demands in perioperative volume requirements due to the disparity between donor and recipient in renal blood flow. We evaluated transfusion practices at a single tertiary institution with special consideration of kidney graft size, hypothesizing that oversize graft kidneys might lead to a quantifiable increased need of blood transfusion in smaller recipients. Retrospective analysis of all patients who underwent pediatric RT from January 2004 to June 2014 at a tertiary pediatric centre was performed. Variables analyzed included patient age, weight, pre- and postoperative Hb concentration, graft size, EBL, amount of intraoperative blood transfusion, and preoperative use of erythropoietin. Based on graft size in relation to patient's age, a SMR and an OvR were identified. A subcohort of age-matched pairs was used to allow for comparison between groups. We calculated the expected procedure- and transfusion-induced changes in Hb and compared these changes to the observed difference in pre- vs postoperative Hb to assess the influence of graft size on transfusion requirements. RT was performed in 188 pediatric recipients during the study period. In the matched cohort, percentage of transfused patients during transplantation in the OvR group was more than double compared with SMR (89% vs 39%, P < .001); similarly, the median number of transfused PRBC units in OvR was 1, while the median of SMR did not receive transfusion (P < .001). The difference between expected (calculated) and observed change in Hb was significantly higher in OvR with a median of 1.9 g/dL compared with SMR with a median of 1.0 g/dL (P = .026). Correspondingly, the calculated median volume taken up by a regular size kidney was significantly higher with 213 mL compared with 313 mL (P = .031) taken up by an oversize graft kidney. Median estimated intraoperative blood loss was significantly higher in OvR than in SMR (6.9 mL/kg, vs 5.3 mL/kg, respectively; P = .04). Median postoperative Hb was similar among groups (10.4 g/dL vs 10.6 g/dL for SMR vs OvR, respectively). Transplantation of an oversized kidney in pediatric RT recipients is associated with a quantifiable higher need for blood transfusion. This may be caused by a higher intraoperative EBL and/or greater blood volume sequestered by the larger renal allograft and requires further evaluation.
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http://dx.doi.org/10.1111/petr.13119DOI Listing
May 2018

Routine histopathological examination of the foreskin after circumcision for clinically suspected lichen sclerosus in children: Is it a waste of resources?

Can Urol Assoc J 2018 May 6;12(5):E231-E233. Epub 2018 Feb 6.

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

Introduction: Circumcision is one of the most widely performed procedures in the world. One of the indications for circumcision is lichen sclerosis (LS). The natural history of LS in children is not as well-documented as in adult patients. Surgeons use the appearance of the foreskin or meatus to predict the diagnosis of LS. Indeed, if the diagnosis of LS is made in childhood, does it change management in the long-term? Pathological analysis of the excised foreskin is routinely done if there is suspicion of LS. Our aim is to assess the concordance between the clinical and pathological diagnosis of suspected LS and to assess the need for sending the foreskin for pathological examination.

Methods: We conducted a retrospective chart review of 64 of 420 boys who underwent circumcision in a tertiary children's hospital from June 2005 to June 2014, and who had their foreskin sent for pathology due to the clinical suspicion of LS. Demographics, presenting symptoms, presumed clinical diagnosis, pathological findings, and followup data were collected and analyzed.

Results: Over the review period, 64 patients underwent circumcision for presumed LS. The mean age of the children was 9.7 years (range 3-16.5). All the children who had circumcision for presumed LS diagnosis were symptomatic. LS was confirmed in 47 of 64 foreskins (73.5%). Balanitis xerotica obliterans (BXO) was clinically suspected in 40 (85%) of the 47 patients. The mean followup was 10 months (range 1-15), with seven recurrences (15%) during that period. The recurrences required revision surgery in two patients and five were managed with steroids only.

Conclusions: In our series, the clinical diagnosis correlated with the pathological diagnosis in most cases. A clinical suspicion of LS without routine foreskin pathological assessment will reduces the overall cost to the healthcare system. Appropriate counselling of the patient/parents and their primary caregiver is imperative, as recurrence is common.
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http://dx.doi.org/10.5489/cuaj.4331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966935PMC
May 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

Impact of smartphone digital photography, email, and media communication on emergency room visits post-hypospadias repair.

Can Urol Assoc J 2017 Mar-Apr;11(3-4):E134-E137. Epub 2017 Apr 11.

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

Introduction: Advances in communication technology are shaping our medical practice. To date, there is no clear evidence that this mode of communication will have any effect on unnecessary postoperative emergency room (ER) visits. We aim to evaluate the effect of email and media communication with application of smartphone digital photography on post-hypospadias repair ER visit rates.

Methods: This prospective cohort study included all patients who underwent hypospadias repair performed by a single surgeon from October 2014 to November 2015. Patients were categorized into two groups: Group A consented for smartphone photography and email communication and Group B declined. Reason for ER visits within 30 days postoperatively was assessed by another physician, who was blinded of patient group assignment. The reasons were categorized as: unnecessary ER visit, indicated ER visit, or visit unrelated to hypospadias surgery. Chi-square test and T-test were used for statistical analysis. Relative risk (RR) and corresponding 95% confidence interval (CI) were also calculated. Statistical significance was set at p<0.05.

Results: Over a 14-month period, 96 patients underwent hypospadias repair (81 in Group A, 15 in Group B 5). No significant difference was noted between groups for overall ER return rate (RR 0.46, 95% CI 0.21, 1.0). However, the number of ER visits for wound check not requiring intervention was significantly lower in Group A than in Group B (RR 0.14, 95% CI 0.035, 0.56); likewise, a higher number of ER visits requiring intervention was noted in Group A compared with Group B, although statistically this was not significant (RR 1.67, 95% CI 0.23, 12.21).

Conclusions: Email communication with the use of smartphone digital photography significantly reduced the number of unnecessary ER visits for post-hypospadias wound checks.
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http://dx.doi.org/10.5489/cuaj.4170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434504PMC
April 2017

Single penile incision for combined hypospadias and inguinal surgery: A comparative study.

Can Urol Assoc J 2017 May 9;11(5):E192-E196. Epub 2017 May 9.

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

Introduction: We sought to compare the surgical outcomes of hypospadias repair with correction of inguinal pathology using a single penile incision vs. conventional approach using two incisions.

Methods: This is a retrospective study that reviewed all patients who underwent concurrent surgical repair for both hypospadias and inguinal pathologies between January 2003 and November 2015. Patients were classified into Group A, conventional (inguinal or scrotal and penile incision) approach; or Group B, single penile incision approach. Baseline characteristics, including age, degree of hypospadias, type and laterality of inguinal pathology, operative time, and surgical outcomes, were collected. Between groups, variable comparisons were analyzed using Mann-Whitney U-Test and Fisher-exact test. Statistical significant set at <0.05.

Results: Seventy-six patients (Group A: 40; Group B: 36) were eligible for study. Baseline characteristics of both groups were comparable, with no significant statistical difference. Overall mean operative time for Group A was 139.3 ± 56.2 minutes, while Group B was 107.8 ± 46.7 minutes (Z=2.6; U=470.5; p=0.009). Two patients in Group A and two patients in Group B had testicular ascension, all of which also had hypospadias-related complications (p=1.0). Hypospadias-related complications in Group A included seven urethrocutaneous fistulae and two repair dehiscence. Eight urethrocutaneous fistulae, one urethral stricture, and two repair dehiscence occurred in Group B (p=0.448). Surgical outcome appearance in both groups were comparable, with no statistically significant difference (p=0.466).

Conclusions: Single penile incision for both hypospadias repair and correction of inguinal pathology is a feasible technique and comparable to the conventional approach, with similar surgical outcomes and shorter overall operative time.
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http://dx.doi.org/10.5489/cuaj.4007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426940PMC
May 2017

Evolution of pediatric urology.

Authors:
Walid A Farhat

Can Urol Assoc J 2017 Jan-Feb;11(1-2):13-14

Pediatric Urology, The Hospital for Sick Children, Toronto, ON, Canada.

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http://dx.doi.org/10.5489/cuaj.4419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403680PMC
April 2017

Use of drugs, psychosocial support, and surgery need to be tempered against the reality of natural resolution of bladder and bowel dysfunction in children.

Authors:
Walid A Farhat

Can Urol Assoc J 2017 Jan-Feb;11(1-2Suppl1):S73

University of Toronto, The Hospital for Sick Children, Toronto, ON, Canada.

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http://dx.doi.org/10.5489/cuaj.4383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332241PMC
March 2017