Circumcision and Risk of HIV among Males from Ontario, Canada.

PURPOSE: Randomized trials from Africa demonstrate that circumcision reduces the risk of acquiring human immunodeficiency virus (HIV) among males. However, few studies have examined this association in Western populations. We sought to evaluate the association between circumcision and the risk of acquiring HIV among males from Ontario, Canada. MATERIALS AND METHODS: We conducted a population-based matched cohort study of residents in Ontario, Canada. We identified males born in Ontario who underwent circumcision at any age between 1991 and 2017. The comparison group consisted of age-matched males who did not undergo circumcision. The primary outcome was incident HIV. We used cause-specific hazard models to evaluate the hazard of incident HIV. We performed several sensitivity analyses to evaluate the robustness of our results: matching on institution of birth, varying the minimum followup period, and simulating various false-negative and false-positive thresholds. RESULTS: We studied 569,950 males, including 203,588 who underwent circumcision and 366,362 who did not. The vast majority of circumcisions (83%) were performed prior to age 1 year. In the primary analysis, we found no significant difference in the risk of HIV between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.72 to 1.35). In none of the sensitivity analyses did we find an association between circumcision and risk of HIV. CONCLUSIONS: We found that circumcision was not independently associated with the risk of acquiring HIV among males from Ontario, Canada. Our results are consistent with clinical guidelines that emphasize safe-sex practices and counseling over circumcision as an intervention to reduce the risk of HIV.

Active surveillance for intermediate-risk prostate cancer.

INTRODUCTION: Active surveillance (AS) is an established approach in the management of low-risk, localized prostate cancer. While the use of AS to manage intermediate-risk (IR) disease has gradually increased over time, there remains uncertainty with regards to its safety, with only a minority of IR patients currently being managed with this approach. MATERIALS AND METHODS: We conducted a narrative review based on an analysis of the literature focusing on articles describing AS for IR prostate cancer. We focus on the uncertainty surrounding AS in IR disease by discussing variations in the definitions and guideline recommendations associated with IR disease, and describing the limitations of the evidence from observational studies and randomized trials. CONCLUSION: The safety of AS for IR disease remains unknown, given the lack of randomized trials and the limitations of the current observational studies. Further research is needed to identify select patients with IR prostate cancer that can be managed safely with AS.

Predicting survival after radical prostatectomy: Variation of machine learning performance by race.

BACKGROUND: Robust prediction of survival can facilitate clinical decision-making and patient counselling. Non-Caucasian males are underrepresented in most prostate cancer databases. We evaluated the variation in performance of a machine learning (ML) algorithm trained to predict survival after radical prostatectomy in race subgroups. METHODS: We used the National Cancer Database (NCDB) to identify patients undergoing radical prostatectomy between 2004 and 2016. We grouped patients by race into Caucasian, African-American, or non-Caucasian, non-African-American (NCNAA) subgroups. We trained an Extreme Gradient Boosting (XGBoost) classifier to predict 5-year survival in different training samples: naturally race-imbalanced, race-specific, and synthetically race-balanced. We evaluated performance in the test sets. RESULTS: A total of 68,630 patients met inclusion criteria. Of these, 57,635 (84%) were Caucasian, 8173 (12%) were African-American, and 2822 (4%) were NCNAA. For the classifier trained in the naturally race-imbalanced sample, the F1 scores were 0.514 (95% confidence interval: 0.513-0.511), 0.511 (0.511-0.512), 0.545 (0.541-0.548), and 0.378 (0.378-0.389) in the race-imbalanced, Caucasian, African-American, and NCNAA test samples, respectively. For all race subgroups, the F1 scores of classifiers trained in the race-specific or synthetically race-balanced samples demonstrated similar performance compared to training in the naturally race-imbalanced sample. CONCLUSIONS: A ML algorithm trained using NCDB data to predict survival after radical prostatectomy demonstrates variation in performance by race, regardless of whether the algorithm is trained in a naturally race-imbalanced, race-specific, or synthetically race-balanced sample. These results emphasize the importance of thoroughly evaluating ML algorithms in race subgroups before clinical deployment to avoid potential disparities in care.

Medication use and kidney cancer survival: A population-based study.

Several studies demonstrate that use of commonly prescribed medications is associated with improved survival in various malignancies. Methods of classifying medication use in many of these studies, however, do not account for intermittent or cumulative use. Moreover, there are limited data in kidney cancer. Therefore, we performed a population-based cohort study utilizing healthcare databases in Ontario, Canada. We identified patients aged ≥65 with an incident diagnosis of kidney cancer between 1997 and 2013 and examined use of nine putative anti-neoplastic medications using prescription claims. Cox proportional hazard models evaluated the association of medication exposure on cancer-specific and overall survival. We conducted three separate analyses: the effect of cumulative duration of exposure to the study medications on outcomes, the effect of current exposure (in a binary nature) and the effect of exposure at diagnosis. During the 16-year study period, we studied 9,124 patients. Increasing cumulative use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs) and selective serotonin reuptake inhibitors were associated with markedly improved cancer-specific survival; increasing use of NSAIDs was associated with markedly improved overall survival. These results were generally discordant with analyses evaluating the effect of current use and exposure at diagnosis. In conclusion, pharmacoepidemiology studies may be sensitive to the method of analysis; cumulative use analyses may be the most robust as it accounts for intermittent use and supports a dose-outcome relationship. Prospective studies are needed to confirm whether patients diagnosed with kidney cancer should be started on an angiotensin-converting enzyme inhibitor, NSAID or selective serotonin reuptake inhibitor to improve survival.

Critical appraisal of the application of propensity score methods in the urology literature.

OBJECTIVES: To determine whether studies that used propensity score (PS) methods in the urology literature provide sufficient detail to allow scientific reproducibility and whether appropriate statistical tests were used to obtain valid measures of effect. MATERIALS AND METHODS: We searched OVID Medline and the Science Citation Index from inception to November 2016 to identify studies that used PS methods in five general urology journals. From each included article, we extracted pertinent information related to the PS methodology, such as estimation of the PS, whether balance diagnostics were performed, and the statistical analysis performed. RESULTS: We identified 114 articles for inclusion. Matching on the PS was the most common method used (62 studies, 54.4%). Of all studies, 103 (90.4%) described which covariates were used to estimate the PS; however, only 24 provided justification for the selected covariates. Although the majority of studies (70.2%) performed some sort of diagnostic evaluation to assess balance, few studies (24.6%) used appropriate methods for balance assessment. Only four (6.4%) studies that used PS matching provided sufficient detail to replicate the matching strategy. Finally, the majority (77.4%) of studies that used PS matching explicitly used inappropriate statistical methods to estimate the effect of an exposure on an outcome. CONCLUSIONS: In the urology literature PS methods were poorly described and implemented. We provide recommendations for improvement to allow scientific reproducibility and obtain valid measures of effect from their use.

Medication use and survival in diabetic patients with kidney cancer: A population-based cohort study.

Survival rates in kidney cancer have improved little over time, and diabetes may be an independent risk factor for poor survival in kidney cancer. We sought to determine whether medications with putative anti-neoplastic properties (statins, metformin and non-steroidal anti-inflammatory drugs (NSAIDs)) are associated with survival in diabetics with kidney cancer. We conducted a population-based cohort study utilizing linked healthcare databases in Ontario, Canada. Patients were aged 66 or older with newly diagnosed diabetes and a subsequent diagnosis of incident kidney cancer. Receipt of metformin, statins or NSAIDs was defined using prescription claims. The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality. We used multivariable Cox proportional hazard regression, with medication use modeled with time-varying and cumulative exposure analyses to account for intermittent use. During the 14-year study period, we studied 613 patients. Current statin use was associated with a markedly reduced risk of death from any cause (adjusted hazard ratio 0.74; 95% CI 0.59-0.91) and death due to kidney cancer (adjusted hazard ratio 0.71; 95% CI 0.51-0.97). However, survival was not associated with current use of metformin or NSAIDs, or cumulative exposure to any of the medications studied. Among diabetic patients with kidney cancer, survival outcomes are associated with active statin use, rather than total cumulative use. These findings support the use of randomized trials to confirm whether diabetics with kidney cancer should be started on a statin at the time of cancer diagnosis to improve survival outcomes.

Lymph Node Yield in Primary Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumors.

PURPOSE: The number of lymph nodes removed at surgery for various malignancies has diagnostic and prognostic value. However, there are limited data on the significance of the number of nodes removed at retroperitoneal lymph node dissection performed for testicular nonseminoma germ cell tumors. MATERIALS AND METHODS: From 1979 to 2012 primary open retroperitoneal lymph node dissection was performed by a single experienced surgeon for clinical stage I/II testicular nonseminoma germ cell tumor in 157 patients. Node count was available in 111 cases (71%). Factors associated with total node count and nodes with viable cancer were assessed by linear regression. The association between node count and time to relapse was assessed by multivariate Cox proportional hazards models controlled for adjuvant chemotherapy. RESULTS: The median total lymph node count was 28 (IQR 19-38). Patient age, cancer laterality, body mass index, clinical stage, time from orchiectomy to retroperitoneal lymph node dissection, pathologist and lymph node dissection year were not associated with total lymph node count. A viable germ cell tumor was found in 70 patients (63%). Total node yield was not associated with nodal cancer metastasis. After lymph node dissection 17 patients (16%) received adjuvant chemotherapy. At a median 57-month followup 18 cases (17%) relapsed after primary retroperitoneal lymph node dissection. Increasing total node count was associated with a decreased risk of relapse on univariate and multivariate analysis (HR 0.96, 95% CI 0.92-0.99, p = 0.03 and HR 0.94, 95% CI 0.89-0.99, p = 0.017, respectively). CONCLUSIONS: No analyzed clinical or pathological variable was associated with the node yield of primary retroperitoneal lymph node dissection. However, there may be a relationship between the total node yield at retroperitoneal lymph node dissection and the risk of relapse.

Surgical outcomes in the management of isolated nodal recurrences: a multicenter, international retrospective cohort.

PURPOSE: We report a multicenter international cohort representing what is to our knowledge the largest surgical experience with managing isolated retroperitoneal nodal recurrence of renal cell carcinoma, a unique subset of locoregional disease, yet to be described in detail. MATERIALS AND METHODS: Patients with isolated nodal recurrence of pTanyN+M0 disease after nephrectomy were identified by retrospective chart review at 3 independent institutions. Progression-free survival was estimated by the Kaplan-Meier method and used to compare survival outcomes between primary T(1-2)N(any)M0 and T3N(any)M0 tumors as well as clear cell and nonclear cell histology renal cell carcinoma. RESULTS: A total of 22 patients met study inclusion criteria. Median time to local postoperative recurrence was 31.5 months (IQR 12.9-43.3). After resection of isolated nodal recurrence 10 patients (46%) had a secondary recurrence at a median of 11.2 months (IQR 8.1-18.4), of whom 2 (9%) died of the disease. Overall median progression-free survival was 12.7 months, including 24.8 months for T(1-2)N(any)M0 tumors, 9.9 months for T3N(any)M0 tumors, and 13.4 and 17.6 months for clear and nonclear cell renal cell carcinoma, respectively. CONCLUSIONS: Surgical resection represents the best curative option for patients who present with isolated retroperitoneal lymph node recurrence of renal cell carcinoma. Durable postoperative progression-free survival is attainable in many patients regardless of histology or clinical TNM stage. In addition, our cohort showed a lower renal cell carcinoma related mortality rate than in previous series of local metastasis. As such, all patients free of precluding comorbidities should be considered candidates for complete surgical resection performed by an experienced genitourinary surgeon.

Surgeon-level versus hospital-level quality variance in kidney cancer surgery.

PURPOSE: To determine whether variance in kidney cancer surgery quality indicators (QIs) is most impacted by surgeon-level or hospital-level factors in order to inform quality improvement initiatives. MATERIALS AND METHODS: The ICES and Veterans Affairs (VA) databases were queried for patients undergoing surgery for localized kidney cancer. Kidney cancer surgery QIs were defined within each cohort. Quality of care was benchmarked at a surgeon- vs. hospital-level to identify statistical outliers, using available clinicopathological data to adjust for differences in case-mix. Variance between surgeons and hospitals was calculated for each QI using a random-effects model. RESULTS: The QI with the greatest amount of variance explained by hospital and surgeon-level factors was proportion of cases performed with minimally invasive surgery (MIS). The majority of this variance was due to surgeon-level factors for both the VA and ICES cohorts. The proportion of cases performed using an MIS approach was also the QI with the greatest number of outlier hospitals and surgeons compared to the average performance. The proportion of partial nephrectomies performed for patients at risk of chronic kidney disease was the QI with the greatest amount of variance due to hospital-level factors for the ICES cohort. CONCLUSIONS: The proportion of localized kidney cancer cases performed using an MIS approach is the QI requiring the greatest attention. Quality improvement initiatives should focus on surgeon-level factors to increase the number of MIS cases being performed for patients with localized renal masses.

Association of BCG Vaccine Treatment With Death and Dementia in Patients With Non-Muscle-Invasive Bladder Cancer.

Importance: The BCG vaccine-used worldwide to prevent tuberculosis-confers multiple nonspecific beneficial effects, and intravesical BCG vaccine is currently the recommended treatment for non-muscle-invasive bladder cancer (NMIBC). Moreover, BCG vaccine has been hypothesized to reduce the risk of Alzheimer disease and related dementias (ADRD), but previous studies have been limited by sample size, study design, or analyses. Objective: To evaluate whether intravesical BCG vaccine exposure is associated with a decreased incidence of ADRD in a cohort of patients with NMIBC while accounting for death as a competing event. Design, Setting, and Participants: This cohort study was performed in patients aged 50 years or older initially diagnosed with NMIBC between May 28, 1987, and May 6, 2021, treated within the Mass General Brigham health care system. The study included a 15-year follow-up of individuals (BCG vaccine treated or controls) whose condition did not clinically progress to muscle-invasive cancer within 8 weeks and did not have an ADRD diagnosis within the first year after the NMIBC diagnosis. Data analysis was conducted from April 18, 2021, to March 28, 2023. Main Outcomes and Measures: The main outcome was time to ADRD onset identified using diagnosis codes and medications. Cause-specific hazard ratios (HRs) were estimated using Cox proportional hazards regression after adjusting for confounders (age, sex, and Charlson Comorbidity Index) using inverse probability scores weighting. Results: In this cohort study including 6467 individuals initially diagnosed with NMIBC between 1987 and 2021, 3388 patients underwent BCG vaccine treatment (mean [SD] age, 69.89 [9.28] years; 2605 [76.9%] men) and 3079 served as controls (mean [SD] age, 70.73 [10.00] years; 2176 [70.7%] men). Treatment with BCG vaccine was associated with a lower rate of ADRD (HR, 0.80; 95% CI, 0.69-0.99), with an even lower rate of ADRD in patients aged 70 years or older at the time of BCG vaccine treatment (HR, 0.74; 95% CI, 0.60-0.91). In competing risks analysis, BCG vaccine was associated with a lower risk of ADRD (5-year risk difference, -0.011; 95% CI, -0.019 to -0.003) and a decreased risk of death in patients without an earlier diagnosis of ADRD (5-year risk difference, -0.056; 95% CI, -0.075 to -0.037). Conclusions and Relevance: In this study, BCG vaccine was associated with a significantly lower rate and risk of ADRD in a cohort of patients with bladder cancer when accounting for death as a competing event. However, the risk differences varied with time.

A machine learning approach to predict progression on active surveillance for prostate cancer.

PURPOSE: Robust prediction of progression on active surveillance (AS) for prostate cancer can allow for risk-adapted protocols. To date, models predicting progression on AS have invariably used traditional statistical approaches. We sought to evaluate whether a machine learning (ML) approach could improve prediction of progression on AS. PATIENTS AND METHODS: We performed a retrospective cohort study of patients diagnosed with very-low or low-risk prostate cancer between 1997 and 2016 and managed with AS at our institution. In the training set, we trained a traditional logistic regression (T-LR) classifier, and alternate ML classifiers (support vector machine, random forest, a fully connected artificial neural network, and ML-LR) to predict grade-progression. We evaluated model performance in the test set. The primary performance metric was the F1 score. RESULTS: Our cohort included 790 patients. With a median follow-up of 6.29 years, 234 developed grade-progression. In descending order, the F1 scores were: support vector machine 0.586 (95% CI 0.579 - 0.591), ML-LR 0.522 (95% CI 0.513 - 0.526), artificial neural network 0.392 (95% CI 0.379 - 0.396), random forest 0.376 (95% CI 0.364 - 0.380), and T-LR 0.182 (95% CI 0.151 - 0.185). All alternate ML models had a significantly higher F1 score than the T-LR model (all p <0.001). CONCLUSION: In our study, ML methods significantly outperformed T-LR in predicting progression on AS for prostate cancer. While our specific models require further validation, we anticipate that a ML approach will help produce robust prediction models that will facilitate individualized risk-stratification in prostate cancer AS.

Preoperative anemia is associated with increased radical cystectomy complications.

PURPOSE: The impact of anemia in postoperative complications following radical cystectomy (RC) is not completely elucidated and its association with direct hospital costs has not been characterized in depth. Our goal is to determine the association between anemia, 90-day surgical complications and the expenditure attributed to preoperative anemia in patients undergoing RC. MATERIALS AND METHODS: We captured all patients who underwent RC between 2003 and 2017 using the Premier Hospital Database (Premier Inc, Charlotte, NC). Patient, hospital and surgical characteristics were evaluated. Anemia was defined by a corresponding diagnostic code that was present on admission prior to RC. Unadjusted patients' demographic characteristics with and without anemia, hospital and surgeon characteristics were compared, and multivariable regression models were developed to evaluate 90-day complications and total direct hospital costs. RESULTS: The cohort included 83,470 patients that underwent RC between 2003 and 2017 and 11% were found to be anemic. On multivariable analysis, preoperative anemia more than doubled the odds of having a complication (odds ratio 2.19 (1.89-2.53)) and significantly increased the risk of major complications (odds ratio 1.51 (1.31-1.75)) at 90-days after RC. Anemic patients had significantly higher 90-days total direct costs due to higher laboratory, pharmacologic, radiology and operating room costs. CONCLUSIONS: Anemic cystectomy patients face a 50% increase in the risk of major complications within the first 90-days after surgery. This increased risk persisted after adjusting for patient, hospital and surgical factors. Our study suggests hematocrit level prior to RC may be used as a pre-exisitng condition for increased risk of surgical complications.

Supply the demand: Assessment of the feasibility of local nonurologists in relieving the burden of chronic indwelling catheters in a low-income country.

INTRODUCTION: Despite the high prevalence rates of urinary retention in sub-Saharan Africa, regional deficiencies in urological care have culminated in inadequate medical management and a backlog of urology cases. Our study examined the efficacy and safety of a surgical camp enlisting local non-urologists performing simple open prostatectomy on the rate of chronic catheter usage secondary to urinary retention. METHODS: We reported on a prospective case series of patients with chronic indwelling catheters who underwent open simple prostatectomy during a one-week urology camp in the Machinga District of Malawi. All operations were performed by a locally trained general surgeon and a clinical officer. RESULTS: Twenty-three (47.9%) of 48 male patients with urinary retention assessed for eligibility for open simple prostatectomy were deemed eligible and underwent the procedure. Of the patients who underwent an open simple prostatectomy, histopathological findings demonstrated benign prostatic hyperplasia in 19 patients (82.6%), while six patients (26.1%) had coincidental malignancy. At postoperative followup, the entire cohort was catheter-free and reported regular sexual activity and the ability to return to work, while 87.0% noted improvements in social integration and 34.8% cited higher self-esteem. Two patients required treatment for infection and one patient experienced fascial dehiscence. Two months following prostatectomy, all patients were catheter-free and able to void independently. CONCLUSIONS: Local surgical practitioners without formal urology training can successfully perform open simple prostatectomy to relieve patients of chronic indwelling catheters and assist in addressing the disease burden in a low-resource setting.

Oncological outcomes in the management of cT1-T2 cN0 penile squamous cell carcinoma.

INTRODUCTION: Squamous cell carcinoma (SCC) of the penis is a rare disease comprising 1% of all male cancer. Options for the management of cT1-T2 cN0 penile SCC include partial penectomy (PP), considered the standard, and brachytherapy (BT), which offers acceptable local disease control and organ preservation. The purpose of our study was to assess and describe the oncological outcome for both treatments in a tertiary care center. METHODS: We performed a contemporary retrospective study of patients with early-stage penile cancer treated surgically or by BT at a tertiary center between 2000 and 2016. Demographic, management, and followup data were obtained from an institutional database. Descriptive statistics and survival analysis using Kaplan-Meier plots were calculated. Local and regional recurrences were compared in both groups (BT vs. PP). RESULTS: A total of 51 patients with cT1-T2N0 penile SCC treated with BT (35) and PP (16) were analyzed. Median followup was 37.1 (13.9-68) and 25.4 months (18-52.3) for the BT and PP groups, respectively. Recurrence developed in seven (20%) patients treated with BT. Median time to recurrence was 35.2 months (range 2.9-95.8). No recurrences were reported in patients treated with PP. Forty-four (86.2%) patients were alive with no evidence of disease at the last followup. Overall survival was 62.7%. Complications after primary tumor treatment were urethral stenosis (15.7%), penile necrosis (7.8%), and local infection (2%). CONCLUSIONS: PP provides acceptable local control with organ preservation in early-stage penile SCC. BT was able to offer organ preservation in 69% of men. Future prospective studies are needed to compare other organ-conserving treatment modalities with PP.

Supply the demand: Assessment of the feasibility of local non-urologists in relieving the burden of chronic indwelling catheters in a low-income country.

INTRODUCTION: Despite the high prevalence rates of urinary retention in sub-Saharan Africa, regional deficiencies in urological care have culminated in inadequate medical management, and a backlog of urology cases. Our study examined the efficacy and safety of a surgical camp enlisting local non-urologists performing simple open prostatectomy on the rate of chronic catheter usage secondary to urinary retention. METHODS: We reported on a prospective case series of patients with chronic indwelling catheters who underwent open simple prostatectomy during a one-week urology camp in the Machinga District of Malawi. All operations were performed by a locally trained general surgeon and a clinical officer. RESULTS: Twenty-three (47.9%) of 48 male patients with urinary retention assessed for eligibility for open simple prostatectomy were deemed eligible and underwent the procedure. Of the patients who underwent an open simple prostatectomy, histopathological findings demonstrated benign prostatic hyperplasia in 19 patients (82.6%), while six patients (26.1%) had coincidental malignancy. At postoperative followup, the entire cohort was catheter-free and reported regular sexual activity and the ability to return to work, while 87.0% noted improvements in social integration and 34.8% cited higher self-esteem. Two patients required treatment for infection and one patient experienced fascial dehiscence. Two months following prostatectomy, all patients were catheter-free and able to void independently. CONCLUSIONS: Local surgical practitioners without formal urology training can successfully perform open simple prostatectomy to relieve patients of chronic indwelling catheters and assist in addressing the disease burden in a low-resource setting.

Long-term outcomes after radical or partial nephrectomy for T1a renal cell carcinoma: A population-based study.

INTRODUCTION: The benefit of partial nephrectomy (PN) compared to radical nephrectomy (RN) for T1a renal cell carcinoma (RCC) remains uncertain, with observational studies conflicting with level 1 evidence. Therefore, the purpose of this population-based study was to compare long-term outcomes in patients undergoing PN or RN for T1a RCC. METHODS: We studied 5670 patients in Ontario, Canada undergoing PN or RN for T1a RCC. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS), chronic kidney disease (CKD), renal replacement therapy, and myocardial infarction (MI). We used multivariable Cox proportional hazard models to evaluate the association between PN or RN and these outcomes. A sensitivity analysis was performed in patients with a preoperative serum creatinine available. RESULTS: Median followup was 77 months. Compared to RN, PN was associated with significantly improved OS (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.63-0.84), reduced risk of CKD (HR 0.18, 95% CI 0.12-0.27), and improved CSS (HR 0.45, 95% CI 0.30-0.65). The risk of MI was not significantly different between groups (HR 0.91, 95% CI 0.62-1.34). Few patients (n=15) required renal replacement therapy. In the sensitivity analysis, the association between type of surgery and OS and CKD persisted, while the association with CSS did not. CONCLUSIONS: Our study found that in patients undergoing surgery for T1a RCC, PN was associated with improved OS and reduced risk of CKD compared to RN. However, few patients in either group required renal replacement therapy.

The effect of ethnicity on semen analysis and hormones in the infertile patient.

INTRODUCTION: We aimed to study the association of ethnicity on semen parameters and hormones in patients presenting with infertility. METHODS: Data from men presenting for infertility assessment were prospectively collected and retrospectively reviewed. Demographic and clinical history was self-reported. Semen analysis included volume, count, motility, morphology, and vitality. The 2010 World Health Organization cutoffs were used. Baseline total testosterone and follicle-stimulating hormone (FSH) levels were recorded. Ethnicity data was classified as Caucasian, African Canadian, Asian, Indo-Canadian, Native Canadian, Hispanic, and Middle Eastern. All patients with complete data were included and statistical analysis was performed. RESULTS: A total of 9079 patients were reviewed, of which 3956 patients had complete data. Of these, 839 (21.2%) were azoospermic. After adjusting for age, African Canadians (odds ratio [OR] 1.70; 95% confidence interval [CI] 1.28-2.25) and Asians (1.34; 95% CI 1.11-1.62) were more likely to be azoospermic compared to Caucasians. Similarly, African Canadians (OR 1.75; 95% CI 1.33-2.29) were more likely to be oligospermic and Asians (OR 0.82; 95% CI 0.70-0.97) less likely to be oligospermic. Low volume was found in African Canadian (OR 1.42; 95% CI 1.05-1.91), Asians (OR 1.23; 95% CI 1.01-1.51), and Indo-Canadians (OR 1.47; 95% CI 1.01-2.13). Furthermore, Asians (OR 0.73; 95% CI 0.57-0.93) and Hispanics (OR 0.58; 95% CI 034-0.99) were less likely to have asthenospermia. Asians (OR 0.73; 95% CI 0.57-0.94) and Indo-Canadians (OR 0.58; 95% CI 0.35-0.99) were less likely to have teratozospermia. No differences were seen for vitality. No differences were seen for FSH levels, however, Asians (p<0.01) and Indo-Canadians (p<0.01) were more likely to have lower testosterone. CONCLUSIONS: Our study illustrates that variations in semen analyses and hormones exist in men with infertility. This may provide insight into the workup and management for infertile men from different ethnicities.

Metformin Use and Kidney Cancer Survival Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVES: Metformin has been associated with improved survival outcomes in various malignancies. However, studies in kidney cancer are conflicting. We performed a systematic review and meta-analysis to evaluate the association between metformin and kidney cancer survival. MATERIALS AND METHODS: We searched Medline and EMBASE databases from inception to June 2017 to identify studies evaluating the association between metformin use and kidney cancer survival outcomes. We evaluated risk of bias with the Newcastle-Ottawa scale. We pooled hazard ratios (HRs) for recurrence-free, progression-free, cancer-specific, and overall survival using random effects models, and explored heterogeneity with metaregression. We evaluated publication bias through Begg's and Egger's tests, and the trim and fill procedure. RESULTS: We identified 9 studies meeting inclusion criteria, collectively involving 7426 patients. Five studies were at low risk of bias. The direction of association for metformin use was toward benefit for recurrence-free survival (HR, 0.99; 95% confidence interval [CI], 0.36-2.74), progression-free survival (pooled HR, 0.84; 95% CI, 0.66-1.07), cancer-specific (pooled HR, 0.72; 95% CI, 0.48-1.09), and overall survival (pooled HR, 0.73; 95% CI, 0.50-1.09), though none reached statistical significance. Metaregression found no study-level characteristic to be associated with the effect size, and there was no strong evidence of publication bias for any outcome. CONCLUSIONS: There is no evidence of a statistically significant association between metformin use and any survival outcome in kidney cancer. We discuss the potential for bias in chemoprevention studies and provide recommendations to reduce bias in future studies evaluating metformin in kidney cancer.

Treatment of Relapse of Clinical Stage I Nonseminomatous Germ Cell Tumors on Surveillance.

PURPOSE: Active surveillance (AS) for testicular nonseminomatous germ cell tumors (NSGCT) is widely used. Although there is no consensus for optimal treatment at relapse on surveillance, globally patients typically receive chemotherapy. We describe treatment of relapses in our non-risk-adapted NSGCT AS cohort and highlight selective use of primary retroperitoneal lymph node dissection (RPLND). METHODS: From December 1980 to December 2015, 580 patients with clinical stage I NSGCT were treated with AS, and 162 subsequently relapsed. First-line treatment was based on relapse site and extent. Logistic regression was used to explore factors associated with need for multimodal therapy on AS relapse. RESULTS: Median time to relapse was 7.4 months. The majority of relapses were confined to the retroperitoneum (66%). After relapse, first-line treatment was chemotherapy for 95 (58.6%) and RPLND for 62 (38.3%), and five patients (3.1%) underwent other therapy. In 103 (65.6%), only one modality of treatment was required: chemotherapy only in 58 of 95 (61%) and RPLND only in 45 of 62 (73%). Factors associated with multimodal relapse therapy were larger node size (odds ratio, 2.68; P = .045) in patients undergoing chemotherapy and elevated tumor markers (odds ratio, 6.05; P = .008) in patients undergoing RPLND. When RPLND was performed with normal markers, 82% required no further treatment. Second relapse occurred in 30 of 162 patients (18.5%). With median follow-up of 7.6 years, there were five deaths (3.1% of AS relapses, but 0.8% of whole AS cohort) from NSGCT or treatment complications. CONCLUSION: The retroperitoneum is the most common site of relapse in clinical stage I NSGCT on AS. Most are cured by single-modality treatment. RPLND should be considered for relapsed patients, especially those with disease limited to the retroperitoneum and normal markers, as an option to avoid chemotherapy.