Factors associated with an increased risk of recurrence in patients diagnosed with high-grade endometrial cancer undergoing minimally invasive surgery: A study of the society of gynecologic oncology of Canada (GOC) community of practice (CoP).

BACKGROUND: Minimally invasive surgery (MIS) is a standard surgical approach for comprehensive surgical staging in women with endometrial cancer. As rates and complexity of MIS are steadily increasing, it is important to identify potential risk factors which may be associated with this approach. This study evaluates the impact of local factors on the risk of disease recurrence. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) who underwent MIS between 2012 and 2016 at eight Canadian centers. Data was collected from medical records. The 75th percentile was calculated for estimated uterine volume and weight. All recurrences were categorized into two groups; intra-abdominal vs. extra-abdominal. To search for significant covariates associated with recurrence-free survival a Cox proportional hazard model was performed. RESULTS: A total of 758 patients were included in the study. Intra-uterine manipulator was used in 497 (35.8%) of patients. Vaginal lacerations were documented in 9.1%. Median follow-up was 30.5 months (interquartile range 20-47). There were 157 who had disease recurrence (20.71%), including 92 (12.14%) intra-abdominal and 60 (7.92%) extra-abdominal only recurrences. In univariate analysis myometrial invasion, LVI, stage, uterine volume and weight > 75th percentile and chemotherapy were associated with increased risk of intra-abdominal recurrence. In multivariable analysis only stage, and specimen weight > 75th percentile (OR 2.207, CI 1.123-4.337) remained significant. Uterine volume, and weight were not associated with increased risk of extra-abdominal recurrences. CONCLUSION: For patients diagnosed with HGEC undergoing MIS, extracting a large uterus is associated with a significantly increased risk for intra-abdominal recurrence.

Evaluating the diagnostic performance of preoperative endometrial biopsies in patients diagnosed with high grade endometrial cancer: A study of the Society of Gynecologic Oncology (GOC) Community of Practice (CoP).

BACKGROUND: High grade cancers account for a disproportionate number of recurrences in patients with endometrial cancer. Accurately identifying these cases on endometrial biopsies allows for better surgical planning. This study evaluates the diagnostic accuracy of general pathologists (GP) compared to gynecological pathologists (GYNP) in interpreting preoperative biopsies. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) between 2012 and 2016 at eight Canadian cancer centres. Data was collected from medical records. Pre-operative biopsies were categorized into groups; biopsies read by GP, GYNP and GP reviewed by GYNP. Rates of HGEC on pre-operative biopsy were calculated. Fisher exact test was used to compare differences between the groups. Univariate logistic regression analysis was conducted for HGEC prediction. RESULTS: Of 1237 patients diagnosed with HGEC, 245 (19.8%) did not have a preoperative diagnosis of high-grade disease. Discordancy was identified in 91/287 (31.71%) of biopsies reported by GP, and in 114/910 (12.53%) of biopsies reported by a GYNP (p < 0.0001). Compared to GP, GYNP were 3.24 (CI 2.36-4.45) times more likely to identify high grade disease on preoperative biopsy. Patients whose biopsy was reported by a GYNP were more likely to have a comprehensive staging procedure (OR 1.77 CI 1.33-2.38) and less likely to receive adjuvant therapy (OR 0.71 CI 0.52-0.96). CONCLUSION: GYNP are more likely to identify HGEC on pre-operative biopsies. Due to high rates of overall discordancy, it is possible that surgical staging procedures should not be based solely on preoperative biopsy. Further strategies to improve pre-operative biopsies' accuracy are needed.

Medusa's Curls: Ureteropelvic Junction Obstruction Secondary to Multiple Long Intraluminal Polyps.

Fibroepithelial polyps represent a rare cause of intrinsic ureteropelvic junction obstruction in the pediatric population, accounting for less than 5% of cases. Herein, we present this peculiar case of a 10-year-old boy with multiple large intraluminal FEPs resembling Medusa's hair and the challenges associated with its subsequent treatment plan.

Society for Fetal Urology Classification vs Urinary Tract Dilation Grading System for Prognostication in Prenatal Hydronephrosis: A Time to Resolution Analysis.

PURPOSE: The Urinary Tract Dilation grading system for prenatal hydronephrosis was introduced to address potential shortcomings of the Society for Fetal Urology classification. Hydronephrosis resolution is an important patient outcome and is frequently discussed during family counseling. We compared these 2 grading systems and their ability to predict time to hydronephrosis resolution. MATERIALS AND METHODS: We prospectively screened 855 patients with prenatal hydronephrosis due to ureteropelvic junction obstruction-like hydronephrosis, nonrefluxing primary megaureter or vesicoureteral reflux between 2009 and 2015. Of the patients 454 were excluded due to surgery, late referral, absence of postnatal dilatation or presence of other anomalies, resulting in 401 eligible patients (of whom 81% were male) to be included for analyses. Hydronephrosis grades collected at baseline and last followup were compared to identify resolution trends through time. Hydronephrosis resolution was defined as renal pelvis anteroposterior diameter 10 mm or less at last followup. Time to resolution was analyzed using Cox proportion regression. RESULTS: Of 401 patients 328 (82%) had resolution during a mean ± SD followup of 24 ± 18 months (maximum 107). Cumulative resolution rate at 3 years was 98% for Society for Fetal Urology grade I hydronephrosis, 87% for grade II, 76% for grade III and 57% for grade IV. The 3-year hydronephrosis resolution rate was 90% for Urinary Tract Dilation postnatal grade 1 (low risk), 81% for grade 2 (intermediate risk) and 71% for grade 3 (high risk). CONCLUSIONS: Patients with distinctive baseline hydronephrosis grades (classified by Society for Fetal Urology or Urinary Tract Dilation system) had significantly different resolution times for hydronephrosis (p <0.001). Counseling families regarding time to resolution of prenatal hydronephrosis should remain the same whether using Society for Fetal Urology or Urinary Tract Dilation grading system.

Quality of reporting for randomized controlled trials in the hypospadias literature: Where do we stand?

INTRODUCTION: To assess the quality of reporting of randomized controlled trials (RCTs) in the hypospadias literature using the 2010 Consolidated Standards of Reporting Trials (CONSORT) statement. It was hypothesized that hypospadias RCTs that contained clear descriptions of key methodological items, allocation concealment, blinding, and sample size justification would have higher overall quality of reporting scores (OQS). MATERIALS AND METHODS: A comprehensive search was conducted through MEDLINE to identify RCTs in hypospadias surgical techniques and postoperative management during the period 1990-2014. Two reviewers independently selected articles, which were evaluated using the CONSORT checklist. An overall quality score (%) was calculated to assess the quality of reporting. In addition, a methodological index score out of 4 was calculated based on the following items: use of intention to treat/sample size justification, allocation concealment, specification of randomization type, and blinding of outcome assessors. RESULTS: Of the 76 initial results, 39 (51%) were excluded due to their predominant focus on anesthesia. After full-text screening, 10 (13%) citations were further excluded because they were case control studies or did not focus on hypospadias techniques, resulting in 27 (36%) studies included for analysis. The mean overall quality score was 37 ± 12% and a median of 36% (range: 14-61%). Fifteen (56%) studies were identified as low quality (score <40%) and 12 (44%) as moderate quality (40-70%). No studies were classified as high quality (>70%). Hypospadias RCTs published between 2007 and 2014 versus those reported before 2007 (44 ± 9% vs 33 ± 11%, P = 0.01), RCTs with a sample size >100 patients versus those <100 (47 ± 8% vs 36 ± 11%, P = 0.01), RCTs that disclosed having received funding versus those that did not (56 ± 4% vs 38 ± 10%, P < 0.01) and RCTs that had proof of biostatistician/epidemiologist support versus those that did not (58 ± 5% vs 36 ± 11%, P = 0.01) had a higher mean OQS. The number of articles that met specific 2010 CONSORT criteria is illustrated in Summary Fig. DISCUSSION: It was found that the contemporary hypospadias literature continues to suffer from suboptimal reporting standards. There seems to be an improvement in the OQS for studies published after 2007 and those with larger sample sizes, usually >100 patients. Nevertheless, none of the studies obtained high quality of reporting (OQS >70%) as per the CONSORT statement checklist. The inadequacies in reporting were related to sample size justifications, randomization method, allocation concealment strategy, blinding, description of subjects lost to follow-up and Intention To Treat (ITT) analysis. These findings were consistent with the poor quality of reporting observed in other surgical fields. CONCLUSIONS: The current overall quality score in hypospadias literature is suboptimal and efforts must be made to improve quality.

Bladder Training Video versus Standard Urotherapy for Bladder and Bowel Dysfunction: A Noninferiority Randomized, Controlled Trial.

PURPOSE: We evaluated whether an animated bladder training video was as effective as standard individual urotherapy in improving bladder/bowel symptoms. MATERIALS AND METHODS: Patients 5 to 10 years old who scored greater than 11 on the bladder/bowel Vancouver questionnaire were included in a noninferiority randomized, controlled trial. Children with vesicoureteral reflux, neuropathic bladder, learning disabilities, recent urotherapy or primary nocturnal enuresis were excluded from analysis. Patients were randomly assigned to receive standard urotherapy or watch a bladder training video in clinic using centralized blocked randomization schemes. Bladder/bowel symptoms were evaluated at baseline and 3-month followup by intent to treat analysis. A sample size of 150 patients ensured a 3.5 difference in mean symptomology scores between the groups, which was accepted as the noninferiority margin. RESULTS: Of 539 screened patients 173 (37%) were eligible for study and 150 enrolled. A total of 143 patients (95%) completed the trial, 5 (4%) were lost to followup and 2 (1%) withdrew. Baseline characteristics were similar between the groups. Baseline mean ± SD symptomology scores were 19.9 ± 5.5 for the bladder training video and 19.7 ± 6.0 for standard urotherapy. At 3 months the mean symptomology scores for the bladder training video and standard urotherapy were reduced to 14.4 ± 6.5 and 13.8 ± 6.0, respectively (p = 0.54). The mean difference was 0.6 (95% CI -1.4-2.6). The upper 95% CI limit of 2.6 did not exceed the preset 3.5 noninferiority margin. CONCLUSIONS: The bladder training video was not inferior to standard urotherapy in reducing bladder/bowel symptoms in children 5 to 10 years old. The video allows families to have free access to independently review bladder training concepts as often as necessary.

Associations of Initial Society for Fetal Urology Grades and Urinary Tract Dilatation Risk Groups with Clinical Outcomes in Patients with Isolated Prenatal Hydronephrosis.

PURPOSE: There are limited comparative data on the predictive value of the 2 most commonly used classification systems, that is SFU (Society for Fetal Urology) hydronephrosis grades and urinary tract dilatation risk groups, in regard to the future risk of surgical intervention and the development of febrile urinary tract infection. We explored this topic in infants with isolated hydronephrosis. MATERIALS AND METHODS: After screening 938 patients with prenatal hydronephrosis from 2009 to 2016 we selected 322 patients with ureteropelvic junction obstruction-like hydronephrosis for study. Hydronephrosis grades were prospectively collected at baseline, surgery and last followup. Gender, circumcision status, antibiotic prophylaxis and renal pelvis anteroposterior diameter were captured. The primary outcome was pyeloplasty and the development of febrile urinary tract infection. Comparative analyses between SFU grades/urinary tract dilatation groups and the primary outcome were performed with the Fisher exact and log rank tests. RESULTS: Mean ± SD age at presentation was 3.3 ± 2.6 months and mean followup was 22 ± 19 months. Pyeloplasty was performed in 32% of patients with SFU III/IV vs 31% with urinary tract dilatation 2/3. The rate of febrile urinary tract infection in patients with SFU III/IV was similar to that in those with urinary tract dilatation group 2/3 (8% vs 10%). Children with SFU III/IV showed a significantly higher rate of surgery than those with SFU I/II (32% vs 2%, p <0.01). Similar findings were seen when using urinary tract dilatation groups to compare patients at low risk (1) vs moderate/high risk (2/3). CONCLUSIONS: Both grading systems equally allowed for proper risk stratification and prediction of clinical outcomes based on baseline ultrasound. They correctly separated most infants who underwent surgery or in whom febrile urinary tract infection developed from those who could be treated nonsurgically. Use of the new urinary tract dilatation classification should not affect how families of children with isolated hydronephrosis are counseled regarding surgical intervention and the risk of febrile urinary tract infection.

Cause and Effect versus Confounding-Is There a True Association between Caudal Blocks and Tubularized Incised Plate Repair Complications?

PURPOSE: We studied the impact of caudal block vs dorsal penile block on the rate of urethrocutaneous fistula and glans dehiscence in children who underwent hypospadias repair. MATERIALS AND METHODS: We retrospectively reviewed the records of 849 consecutive patients who underwent tubularized incised plate repair between 2004 and 2015. A total of 331 cases with incomplete medical records, other techniques and redo repair were excluded. The preference for caudal block was based on anesthesiologist discretion. Age at surgery, meatal location, preoperative testosterone stimulation, type of regional anesthesia (caudal block vs dorsal penile block), degree of ventral curvature, surgeon expertise and complications (urethrocutaneous fistula/glans dehiscence) were captured. Univariate and multivariable analyses were done of risk factors for complications. RESULTS: Median age at surgery was 18 months and median followup was 6 months. Of 518 patients 405 (78%) had distal and 113 (22%) had mid shaft/proximal defects. Complications developed in 37 cases (7%), including urethrocutaneous fistula in 21 (19 with a caudal block and 2 with a dorsal penile block) and glans dehiscence in 16 (13 with a caudal block and 3 with a dorsal penile block). On univariate analysis preoperative testosterone stimulation vs no preoperative testosterone stimulation (13.0% vs 6.2% of cases, p = 0.04), mid shaft/proximal vs distal defects (15.9% vs 4.7%, p <0.01) and caudal block (8.7% vs 3.3%, p = 0.03) were significantly associated with more complications. However, on multivariable analysis the associations of preoperative testosterone stimulation (OR 1.2, 95% CI 0.4-3.7) and caudal block (OR 2.4, 95% CI 0.9-6.4) with complications did not hold. Only the combination of meatal location/ventral curvature remained as an independent risk factor for urethrocutaneous fistula/glans dehiscence (OR 2.4, 95% CI 1.1-5.7, p = 0.04). CONCLUSIONS: Our data indicate that hypospadias severity and not the type of regional anesthesia was the only risk factor significantly associated with postoperative complications. To confirm these findings and provide strong and definitive evidence on this topic a well powered, randomized, controlled trial is clearly required.

From Research Question to Conducting a Randomized Controlled Trial on Continuous Antibiotic Prophylaxis in Prenatal Hydronephrosis: A Rational Stepwise Process.

INTRODUCTION AND OBJECTIVES: Continuous antibiotic prophylaxis (CAP) use to prevent urinary tract infections (UTI) in infants with prenatal hydronephrosis (HN) remains controversial. Lack of consensus guidelines and diverse practice patterns for postnatal management of HN highlight the dire need for higher level of evidence studies. Herein, we aim to describe the steps from developing a well-defined research question to execute a multicentered randomized controlled trial (RCT) to address the issue of CAP use in patients with prenatal HN. MATERIALS AND METHODS: The steps involved were (1) choosing the proper research question, (2) survey of practice patterns and establishing clinical equipoise, (3) systematic review of the literature, (4) reviewing own practice, (5) longitudinal prospective study, (6) pilot study, (7) cost-utility analysis, and (8) definitive RCT (clinical trials registry number: NCT01140516). An update of our previous systematic review was conducted using two electronic databases and gray literature from 2010 to 2015. Eligibility criteria included studies of children <2 years old with postnatally confirmed prenatal HN, receiving CAP or not, and reporting on development of UTIs, capturing information on voiding cystourethrogram result and HN grade. Full-text screening was conducted by two independent reviewers. UTI rates in patients with high-grade HN were compared across different study designs. Finally, blinded comparative analysis of UTI rates between placebo and treatment groups was carried out using chi-square test. RESULTS: UTI rates in patients with high-grade HN by their respective study design were: 25% for systematic review, 20% for retrospective study, 21% for prospective and pilot studies, and 13% for the definitive RCT thus far. Regardless of the type of study design, patients with hydroureteronephrosis had significantly higher (threefold to sixfold) UTI rates than those with isolated HN. Our updated systematic review yielded 486 citations, of which 9 (n = 1987 infants) observational studies met eligibility criteria. CONCLUSION: UTI rates in patients with high-grade HN dropped from 25% in observational studies to 13% in our RCT. This decline in UTI rate demonstrates that study designs lacking strategies to minimize bias are more prone to overestimate treatment effects. These findings highlight the importance of conducting methodologically sound RCTs to answer clinically meaningful questions, such as the one presented here.

The Fate of Primary Nonrefluxing Megaureter: A Prospective Outcome Analysis of the Rate of Urinary Tract Infections, Surgical Indications and Time to Resolution.

PURPOSE: We examined data on a cohort of patients with primary nonrefluxing megaureter to determine risk factors for febrile urinary tract infection, indications for surgery and time to resolution. MATERIALS AND METHODS: The records of patients younger than 24 months with primary nonrefluxing megaureter were prospectively captured from 2008 to 2015. Six a priori defined variables were studied, including gender, circumcision status, hydronephrosis SFU (Society for Fetal Urology) grade (low--1 and 2 vs high--3 and 4), continuous antibiotic prophylaxis use, ureteral dilatation (greater than 11 mm) and tortuosity. Univariate analyses and Cox hazard regression were done for febrile urinary tract infection risk factors. Resolution trends were analyzed using Kaplan-Meier curves. RESULTS: Mean ± SD age at the first clinic visit was 3.7 ± 4 months and mean followup was 26.3 ± 16.6 months. Of 80 patients with primary megaureter 66 (83%) had high grade hydronephrosis, 72 (90%) were male, 21 (26%) were circumcised and 40 (50%) had ureteral dilatation greater than 11 mm at baseline. Overall continuous antibiotic prophylaxis was prescribed to 34 patients (43%) and febrile urinary tract developed infection in 27 (34%) at a mean age of 5.8 months (median 3, range 1 to 24). Cox regression identified uncircumcised male gender (HR 3.4, 95% CI 1.1-10.7, p = 0.04) and lack of continuous antibiotic prophylaxis (HR 4.1, 95% CI 1.3-12.7, p = 0.01) as independent risk factors for febrile urinary tract infection. The 19 surgical patients (24%) had a larger mean ureteral diameter immediately preoperatively than those who did not require surgery (17 ± 5 vs 12 ± 4 mm, p <0.01). Kaplan-Meier curves showed that 85% of primary nonrefluxing megaureters that did not require surgery resolved in a median of 17 months. CONCLUSIONS: Febrile urinary tract infection developed in 34% of patients with primary nonrefluxing megaureter within the first 6 months of life. Circumcision and continuous antibiotic prophylaxis significantly decreased febrile urinary tract infection rates in those infants. Ureteral diameter 17 mm or greater was significantly associated with a higher rate of surgical intervention. Overall 76% of megaureters resolved during a median followup of 19 months.

A pilot randomized controlled trial evaluating the effectiveness of group vs individual urotherapy in decreasing symptoms associated with bladder-bowel dysfunction.

PURPOSE: We determined the feasibility of a definitive trial comparing the effectiveness of group vs individual urotherapy for children with bladder-bowel dysfunction. MATERIALS AND METHODS: Children 6 to 10 years old with bladder-bowel dysfunction were recruited during the course of 1 year. Feasibility data on screening, eligibility, recruitment and protocol compliance rates were collected. Patients with high grade hydronephrosis, vesicoureteral reflux or learning disabilities and those who had previously undergone urotherapy were excluded. Patients were randomized to 1-hour group urotherapy or 15-minute individual urotherapy. Symptoms and quality of life were measured using the Vancouver Nonneurogenic Lower Urinary Tract Dysfunction/Dysfunctional Elimination Syndrome Questionnaire and the Pediatric Incontinence Questionnaire at baseline and at 3 to 6 months of followup. Within/between group comparisons were conducted using t-tests. RESULTS: Of 455 screened children 79 were eligible and 60 were recruited to participate. A total of 24 patients randomized to group urotherapy and 25 randomized to individual urotherapy completed the pilot trial (6 undergoing group and 5 undergoing individual urotherapy withdrew from the study). Symptomology scores between group and individual urotherapy were not different at followup (mean ± SD 14.7 ± 7.9 vs 13.4 ± 6.3, p = 0.54, 95% CI -5.4-2.8). Quality of life scores between patients undergoing group and individual urotherapy at baseline differed (mean ± SD 21.1 ± 10.8 vs 31.0 ± 14.3, p < 0.01, 95% CI 2.7-7.3) but became similar at followup (21.0 ± 14.2 vs 20.1 ± 15.3, p = 0.84, 95% CI -9.4-7.6). Within group analyses demonstrated improvement in symptomology from baseline to followup in patients undergoing group (mean ± SD 3.6 ± 7.6, p = 0.03, 95% CI 0.4-6.8) and individual urotherapy (6.0 ± 5.4, p < 0.01, 95% CI 3.8-8.3). Within group quality of life analyses revealed improvement in Pediatric Incontinence Questionnaire scores from baseline to followup in patients undergoing individual urotherapy (p < 0.01, 95% CI 5.0-16.9) only. CONCLUSIONS: Urotherapy, regardless of modality, effectively improved bladder-bowel dysfunction symptoms. A definitive randomized controlled trial is feasible, considering that a high recruitment rate (76%) for this population has been established.