Improved sperm DNA fragmentation levels in infertile men following very short abstinence of 3-4 hours.

Background: Limited data exists on possible approaches to improve sperm DNA fragmentation index (DFI) when no identifiable cause is found. The effect of short abstinence on sperm parameters has been extensively studied, but rarely reported on the effect on DFI in infertile men. In this study, we aimed to determine whether a second ejaculate provided after very short abstinence demonstrates lower DFI rates in infertile men. Methods: This prospective cohort study was conducted at Mount Sinai Hospital, Toronto, Canada, a tertiary university affiliated hospital. All men having DFI testing in addition to the standard semen analysis were identified via a prospectively collected database. Infertile men were instructed to provide two semen samples 3-4 hours apart (the first sample was given after 2-5 days of abstinence) to test the effect on DFI levels. Data analysis was performed for the comparison of the change in sperm parameters and DFI between samples and between men with DFI above and under 30%. Results: A total of 52 men provided double ejaculates 3-4 hours apart. In the entire group, DFI decreased from 38.9%±21.4% to 35.1%±21.6% in the second sample (P<0.001). Semen volume was lower on the second sample (2.3±1.4 vs. 1.5±0.9 mL, P<0.001), while the remaining parameters did not change. Forty out of 52 patients (76.9%) had improved DFI (average of 6.0±4.0 percentage points). Change in DFI varied with 22/52 (42.3%) and 7/52 (13.5%) of patients found to have decreases in DFI >5% and >10% in the second ejaculate, respectively. For men with DFI of 30-40%, 64% (7/11) of DFIs reduced to the under 30% range. First DFI value was the only parameter associated with DFI decrease to under 30% in multivariate models [odds ratio (OR), 0.62; 95% confidence interval (CI): 0.39-0.98; P=0.04]. Conclusions: This study identified significant improvements in DFI in infertile men providing a second sample after 3-4 hours. Controlled trials are needed to determine if reproductive outcomes are improved using a second ejaculate for infertile men with high initial sperm DFI values.

Comparing Oncological and Perioperative Outcomes of Open versus Laparoscopic versus Robotic Radical Nephroureterectomy for the Treatment of Upper Tract Urothelial Carcinoma: A Multicenter, Multinational, Propensity Score-Matched Analysis.

OBJECTIVES: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). METHODS: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990-2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien-Dindo > 3) were assessed between groups. RESULTS: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan-Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22-2.28, p = 0.001 and HR 1.73, 95%CI 1.22-2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta -1.1, 95% CI -2.2-0.02, p = 0.047 and beta -6.1, 95% CI -7.2-5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31-0.79, p = 0.003 and OR 0.27, 95% CI 0.16-0.46, p < 0.001, respectively). CONCLUSIONS: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

Pentafecta for Radical Nephroureterectomy in Patients with High-Risk Upper Tract Urothelial Carcinoma: A Proposal for Standardization of Quality Care Metrics.

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.

Cost-effectiveness of Retrograde Intrarenal Surgery, Standard and Mini Percutaneous Nephrolithotomy, and Shock Wave Lithotripsy for the Management of 1-2cm Renal Stones.

OBJECTIVE: To perform a cost-effectiveness evaluation comparing the management options for mid-size (1-2cm) renal stones including percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), and shockwave lithotripsy (SWL). METHODS: A Markov model was created to compare cost-effectiveness of PCNL, mini-PCNL, RIRS, and SWL for 1-2cm lower pole (index patient 1) and PCNL, RIRS, and SWL for 1-2 cm non-lower pole (index patient 2) renal stones. A literature review provided stone free, complication, retreatment, secondary procedure rates, and quality adjusted life years (QALYs). Medicare costs were used. The incremental cost-effectiveness ratio (ICER) was compared with a willingness-to-pay(WTP) threshold of $100,000/QALY. One-way and probabilistic sensitivity analyses were performed. RESULTS: At 3 years, costs for index patient 1 were $10,290(PCNL), $10,109(mini-PCNL), $5,930(RIRS), and $10,916(SWL). Mini-PCNL resulted in the highest QALYs(2.953) followed by PCNL(2.951), RIRS(2.946), and SWL(2.943). This translated to RIRS being most cost-effective followed by mini-PCNL(ICER $624,075/QALY) and PCNL(ICER $946,464/QALY). SWL was dominated with higher costs and lower effectiveness. For index patient 2, RIRS dominated both PCNL and SWL. For index patient 1: mini-PCNL and PCNL became cost effective if cost ≤$5,940 and ≤$5,390, respectively. SWL became cost-effective with SFR ≥75% or cost ≤$1,236. On probabilistic sensitivity analysis, the most cost-effective strategy was RIRS in 97%, mini-PCNL in 2%, PCNL in 1%, and SWL in 0% of simulations. CONCLUSION: For 1-2cm renal stones, RIRS is most cost-effective. However, mini and standard PCNL could become cost-effective at lower costs, particularly for lower pole stones.

The Impact of Upper Tract Urothelial Carcinoma Diagnostic Modality on Intravesical Recurrence after Radical Nephroureterectomy: A Single Institution Series and Updated Meta-Analysis.

PURPOSE: Diagnostic ureteroscopic biopsy for upper tract urothelial carcinoma (UTUC) has been hypothesized to increase intravesical recurrence of urothelial carcinoma after radical nephroureterectomy (RNU). Moreover, the impact of ureteroscopy without biopsy or percutaneous biopsy on intravesical recurrence remains unknown. Herein, we compared post-RNU intravesical recurrences across UTUC diagnostic modalities. MATERIALS AND METHODS: Patients undergoing RNU at our institution between 1995 and 2019 were categorized by UTUC diagnostic modality: 1) no ureteroscopy or percutaneous biopsy; 2) percutaneous biopsy; 3) ureteroscopy without biopsy; 4) ureteroscopic biopsy. Intravesical recurrences were compared using Kaplan-Meier analyses and Cox-proportional hazard models. Results of group 4 vs 1 were pooled with the literature using a fixed effects meta-analysis. RESULTS: In a cohort of 834 RNU patients, 210 (25.2%) had undergone no ureteroscopy, 57 (6.6%) percutaneous biopsy, 125 (15.0%) ureteroscopy without biopsy, and 442 (53.0%) ureteroscopic biopsy. Two-year intravesical recurrence rates were 15.0%, 12.7%, 18.4%, and 21.9% for groups 1 through 4, respectively (p=0.09). Multivariable analysis found that group 4 had increased intravesical recurrences (HR 1.40, p=0.04) relative to group 1 while group 2 (HR 1.07, p=0.87) and group 3 (HR 1.15, p=0.54) did not. Group 4 remained associated with intravesical recurrence on subset analyses accounting for post-RNU surveillance cystoscopy frequency. On meta-analysis including 11 other series, ureteroscopic biopsy was associated with intravesical recurrence (HR 1.47, p <0.01). CONCLUSIONS: Ureteroscopic biopsy before RNU, but not percutaneous biopsy or ureteroscopy without biopsy, was associated with increased intravesical recurrence. Clinical trials of intravesical chemotherapy after ureteroscopic biopsy are warranted to reduce intravesical recurrences.

Morphologic Factors Associated With Open Conversion During Holmium Laser Enucleation of the Prostate.

OBJECTIVE: To determine if there is an association between patient body habitus as measured by body mass index (BMI), body surface area (BSA), preoperative prostate volume, postoperative specimen weight, and open conversion with cystotomy or perineal urethrotomy (PU) during holmium laser enucleation of the prostate (HoLEP). We attempt to provide meaningful criteria to assist in preoperative patient counseling. MATERIALS AND METHODS: Three hundred consecutive patients underwent HoLEP between August 3, 2018 and February 20, 2020 by a single surgeon. Patient metrics were recorded in a database including age, height, weight, preoperative prostate volume, postoperative specimen weight, catheter dependence, and transfusion requirement. Nine patients were identified who had cystotomy (8) or PU (1) performed during HoLEP secondary to inability to complete the procedure using standard endoscopic technique. Univariate and multivariate statistical analysis was performed. RESULT: Younger age, higher BMI, higher BSA, and higher estimated prostate volume were associated with increased risk of open conversion during HoLEP. No patient with a BMI under 30 required open conversion. CONCLUSION: Men with BMI >30 kg/m2 or preoperative prostate volume >125 mL should be counseled on the possibility of open conversion with cystotomy or PU. Although the overall risk of conversion is low (3%), the risk may be as high as 10% for patients in the highest quartile of BMI (>30.5 kg/m2) and BSA (>2.2m2).

Sequential administration of Bacillus Calmette-Guerin (BCG) and Electromotive Drug Administration (EMDA) of mitomycin C (MMC) for the treatment of high-grade nonmuscle invasive bladder cancer after BCG failure.

BACKGROUND: There is a need for effective nonsurgical treatment options in patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Guerin (BCG) therapy has failed. OBJECTIVE: We aimed to determine the efficacy of Electromotive Drug Administration (EMDA) of mitomycin C (MMC) with NMIBC after BCG failure. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 26 NMIBC patients in whom BCG therapy failed who received BCG/EMDA-MMC between 2013 and 2017 was performed. All but 4 patients fulfilled the FDA criteria for BCG unresponsive disease. Progression and recurrence-free survival (RFS)were calculated using Kaplan-Meier curves. Progression was defined as development of muscle invasive disease, presence of metastasis on imaging or treatment. We used FDA-defined criteria as complete response (CR) for single-arm trials of BCG-unresponsive patients. RESULTS AND LIMITATIONS: Twenty-six patients were included. Initial pathology was carcinoma in situ (CIS) in 53.8% (14/26), pT1 in 34.6% (9/26), and pTa HG disease in 11.6% (3/26). Twelve of 26 patients progressed (46.2%). Following BCG/EMDA-MMC treatment, progression-free survival rates were 58.3% (95% confidence interval [CI] 41.1-82.1) at 1 year and 48.9% (95% CI 48.9) at 2 years from the date of induction of BCG/EMDA-MMC, respectively. RFS was 41.9% (95% CI 25.9-67.8) at 1 year and 27.2% (95% CI 13.6-54.4) at 2 years. CR at 6, 12, and 18 months was observed in 16 (61.5%), 11 (44.0%), and 7 patients (30.4%), respectively. Side effects included dysuria (19.2%), hematuria (19.2%), and frequency (11.5%). Three patients were admitted for side effects but managed conservatively. Four patients (15.4%) died of bladder cancer over the course of the study. CONCLUSIONS: EMDA-MMC BCG represents a viable option in patients with BCG unresponsive NMIBC with close to 50% progression-free survival at 2 years. However, these patients have a high risk of death from bladder cancer (15% in our cohort at 2 years) thus warranting extremely close surveillance.

A noninvasive urine-based methylation biomarker panel to detect bladder cancer and discriminate cancer grade.

BACKGROUND: Highly sensitive and specific urinary biomarkers for the early detection of bladder cancer (BC) to improve the performance of urinary cytology are needed. OBJECTIVE: To investigate the usefulness of methylation markers in voided urine to identify BC presence and grade. DESIGN, SETTINGS, AND PARTICIPANTS: Using genome-wide methylation strategies in Toronto, Canada and Liège, Belgium, we have identified differentially methylated genes (TWIST1, RUNX3, GATA4, NID2, and FOXE1) in low-grade vs. high-grade BC tissue and urine. We accrued urine samples from 313 patients using a 2:1 ratio in a case-control setting from Toronto, Canada, Halifax, Canada, and Zurich, Switzerland. We studied the usefulness of these 5 methylated genes to identify BC and discriminate cancer grade in voided urine specimens. Urinary cell sediment DNA was evaluated using qPCR-based MethyLight assay. Multivariable logistic regression prediction models were created. RESULTS AND LIMITATIONS: We included 211 BC patients (180 nonmuscle invasive) and 102 controls. In univariate analyses, all methylated genes significantly predicted BC vs. no BC, and high grade vs. low grade (all P < 0.05). In multivariable analysis, NID2, TWIST1, and age were independent predictors of BC (all P < 0.05). Sensitivity of NID2 and TWIST1 to predict BC and BC grade was 76.2% and 77.6%, respectively, whereas specificity was 83.3% and 61.1%, respectively. Multivariable models predicting BC overall and discriminating between high-grade and low-grade BC reached area under the receiver operating characteristics curves of 0.89 and 0.78, respectively. CONCLUSIONS: This multi-centric study in a real life scenario (different countries, techniques, and pathologists) supports the promise of epigenetic urinary markers in noninvasively detecting BC. With sensitivities and specificities in the range of 80%, the overall performance characteristics of this panel of methylated genes probably does not allow such signature to significantly alter clinical care at this stage but is worth further studying for instance in BC surveillance or screening in high-risk populations.

Percutaneous Image-guided Core Needle Biopsy for Upper Tract Urothelial Carcinoma.

OBJECTIVE: To better understand the safety and diagnostic yield of percutaneous core-needle biopsy (PCNB) for upper tract urothelial carcinoma (UTUC). METHODS: Of 444 patients undergoing radical nephroureterectomy (RNU) for UTUC between 2009 and 2017 at our institution, 42 who had PCNB prior to RNU were identified for analysis. Endpoints included safety, diagnostic yield, and concordance with RNU pathology. PCNB specimens were deemed histologically concordant with RNU specimens for cases when cytologic evaluation of biopsy specimen and corresponding pathologic evaluation of RNU specimen both made a histologic diagnosis of urothelial carcinoma. RESULTS: Median tumor size was 3.8 cm (1.2-10.2 cm). All lesions arose from the pelvicalyceal system. CT-guidance was utilized in 52% (n = 22), and ultrasound-guidance in 48% (n = 20). Relative to RNU pathology, 95% of PCNBs demonstrated histologic concordance. Histologic grade was provided in 69% (n = 29) of PCNBs, with a 90% (n = 26) concordance with surgical pathology. Grades 1-2 and 3 complications occurred in 14.3% (n = 6) and 2.4% (n = 1), respectively. At a median follow-up of 28.2 months (range, 1.2-97.1 months) after biopsy, no cases of radiographic tract seeding were identified. CONCLUSION: In our cohort of 42 patients undergoing RNU for UTUC, PCNB appeared a safe diagnostic tool with high histologic yield and grade concordance. With greater than 2 years of follow-up, no cases of tract seeding were identified.

The burden of urological disease in Zomba, Malawi: A needs assessment in a sub-Saharan tertiary care center.

INTRODUCTION: A large part of the developing world continues to lack access to surgical care. Urology remains one of the least represented surgical subspecialties in global health. To begin understanding the burden of urological illness in sub-Saharan Africa, we sought to characterize all patients presenting to a tertiary care hospital in Malawi with a urological diagnosis or related complaint in the past year. METHODS: Retrospective review of the surgical clinic and surgical theater record books at Zomba Central Hospital (ZCH) was performed over a one-year time span. Patients presenting with urological diagnoses or undergoing a urological procedure under local or general anesthetic in the operating theater were identified and entered into a database. RESULTS: We reviewed 440 clinical patients. The most common clinical presentations were for urinary retention (34.7%) and lower urinary tract symptoms (15.5%). A total of 182 surgical cases were reviewed. The most common diagnoses for surgical patients were urethral stricture disease (22%), bladder masses (17%), and benign prostatic hyperplasia (BPH) symptoms (14.8%). Urethral stricture-related procedures, including direct visual internal urethrotomy and urethral dilatation, were the most common (14.2% and 7.7%, respectively). BPH-related procedures, including simple prostatectomy and transurethral resection of the prostate were the second most common (6.7% and 8.2%, respectively). CONCLUSIONS: Urethral stricture disease, BPH, and urinary retention represent the clinical diagnoses with the highest burden of visits. Despite these numbers, few definitive procedures are performed annually. Further focus on urological training in sub-Saharan Africa should focus on these conditions and their surgical management.

Prevalence and Management of Incidental Small Testicular Masses Discovered on Ultrasonographic Evaluation of Male Infertility.

PURPOSE: We report the safety of surveillance of small testicular masses incidentally discovered during evaluation of male infertility. MATERIALS AND METHODS: We retrospectively reviewed a prospectively collected database to identify patients with male infertility found to have incidental small testicular masses (hypoechoic lesions less than 10 mm) on scrotal ultrasound. The men were offered close surveillance with interval imaging and office followup. Patient and imaging characteristics were collected to compare the surveillance and surgical groups with additional comparisons between benign and malignant pathologies to elucidate predictors of underlying malignancy. RESULTS: Of 4,088 men in whom scrotal ultrasound was completed for male infertility evaluation 120 (2.9%) were found to have a subcentimeter testicular mass. Average followup was 1.30 years (range 0.1 to 16.9). A total of 18 men (15%) proceeded to extirpative surgery while 102 remained on surveillance at last followup. In those with at least 1 month of followup the mean lesion growth rate was -0.01 mm per year. Reasons for surgery included testicular exploration for infertility, mass growth, positive tumor markers, history of testis cancer, concerning imaging characteristics and patient choice. Six of the 18 men who underwent surgery were found to have malignancy, which was seminoma in all. All malignant lesions were greater than 5 mm on initial imaging and demonstrated vascularity, although size and vascularity were not significantly different from those of benign lesions on final pathology findings. No patients demonstrated advanced or recurrent disease. CONCLUSIONS: Small testicular masses are not uncommon, especially in the infertile male population. Most of these masses do not show significant growth during long-term evaluation and can be safely surveilled with close followup.

Association Between Use of Antithrombotic Medication and Hematuria-Related Complications.

Importance: Antithrombotic medications are among the most commonly prescribed medications. Objective: To characterize rates of hematuria-related complications among patients taking antithrombotic medications. Design, Setting, and Participants: Population-based, retrospective cohort study including all citizens in Ontario, Canada, aged 66 years and older between 2002 and 2014. The final follow-up date was December 31, 2014. Exposures: Receipt of an oral anticoagulant or antiplatelet medication. Main Outcomes and Measures: Hematuria-related complications, defined as emergency department visit, hospitalization, or a urologic procedure to investigate or manage gross hematuria. Results: Among 2 518 064 patients, 808 897 (mean [SD] age, 72.1 [6.8] years; 428 531 [53%] women) received at least 1 prescription for an antithrombotic agent over the study period. Over a median follow-up of 7.3 years, the rates of hematuria-related complications were 123.95 events per 1000 person-years among patients actively exposed to antithrombotic agents vs 80.17 events per 1000 person-years among patients not exposed to these drugs (difference, 43.8; 95% CI, 43.0-44.6; P < .001, and incidence rate ratio [IRR], 1.44; 95% CI, 1.42-1.46). The rates of complications among exposed vs unexposed patients (80.17 events/1000 person-years) were 105.78 for urologic procedures (difference, 33.5; 95% CI, 32.8-34.3; P < .001, and IRR, 1.37; 95% CI, 1.36-1.39), 11.12 for hospitalizations (difference, 5.7; 95% CI, 5.5-5.9; P < .001, and IRR, 2.03; 95% CI, 2.00-2.06), and 7.05 for emergency department visits (difference, 4.5; 95% CI, 4.3-4.7; P < .001, and IRR, 2.80; 95% CI, 2.74-2.86). Compared with patients who were unexposed to thrombotic agents, the rates of hematuria-related complications were 191.61 events per 1000 person-years (difference, 117.3; 95% CI, 112.8-121.8) for those exposed to both an anticoagulant and antiplatelet agent (IRR, 10.48; 95% CI, 8.16-13.45), 140.92 (difference, 57.7; 95% CI, 56.9-58.4) for those exposed to anticoagulants (IRR, 1.55; 95% CI, 1.52-1.59), and 110.72 (difference, 26.5; 95% CI, 25.9-27.0) for those exposed to antiplatelet agents (IRR, 1.31; 95% CI, 1.29-1.33). Patients exposed to antithrombotic agents, compared with patients not exposed to these drugs, were more likely to be diagnosed as having bladder cancer within 6 months (0.70% vs 0.38%; odds ratio, 1.85; 95% CI, 1.79-1.92). Conclusions and Relevance: Among older adults in Ontario, Canada, use of antithrombotic medications, compared with nonuse of these medications, was significantly associated with higher rates of hematuria-related complications (including emergency department visits, hospitalizations, and urologic procedures to manage gross hematuria).

Germline Mutations in the Kallikrein 6 Region and Predisposition for Aggressive Prostate Cancer.

Background: There is a need for markers that can specifically identify individuals at increased risk of harboring aggressive forms of prostate cancer (PCa). Methods: We surveyed the Kallikrein ( KLK ) region ( KLK 1-15) for single-nucleotide polymorphisms (SNPs) associated with aggressive PCa (Gleason Score ≥ 8) in 1858 PCa patients. Discovery cohorts (Swiss arm of the European Randomized Study of Screening for PCa, n = 379; Toronto, Canada, n = 540) and a validation cohort (Prostate, Lung, Colorectal and Ovarian [PLCO] screening trial, n = 939) were analyzed. Fine-mapping within the KLK region was carried out by genotyping and imputation in the discovery cohort, whereas PLCO data were provided through database of Genotypes and Phenotypes ( dbGaP ). The influence of SNPs of interest on biochemical-free survival was evaluated in a cohort of localized PCa from the International Cancer Genome Consortium (ICGC; n = 130) analyzed with next-generation sequencing. Single- and multi-SNP association studies, as well as haplotype analyses, were performed. All statistical tests were two-sided. Results: Several SNPs in very strong linkage disequilibrium in the KLK 6 region and located within the same haplotype (rs113640578, rs79324425, rs11666929, rs28384475, rs3810287), identified individuals at increased risk of aggressive PCa in both discovery (odds ratio [OR] = 3.51-3.64, 95% confidence interval [CI] = 2.01 to 6.36, P = 1.0x10 -5 -8.4x10 -6 ) and validation (OR = 1.89-1.96, 95% CI = 0.99 to 3.71, P = .04-.05) cohorts. The overall test of haplotype association was highly statistically significant in each cohort ( P = 3.5x10 -4 and .006, respectively) and in the three data sets combined ( P = 2.3x10 -5 ). These germline SNPs independently predicted relapse in the ICGC cohort (hazard ratio = 3.15, 95% CI = 1.57 to 6.34, P = .001). Conclusions: Our fine-mapping study has identified novel loci in the KLK 6 region strongly associated with aggressive PCa.

Renal Tumor Biopsy for Small Renal Masses: A Single-center 13-year Experience.

BACKGROUND: Renal tumor biopsy (RTB) for the characterization of small renal masses (SRMs) has not been widely adopted despite reported safety and accuracy. Without pretreatment biopsy, patients with benign tumors are frequently overtreated. OBJECTIVE: To assess the diagnostic rate of RTBs, to determine their concordance with surgical pathology, and to assess their impact on management. DESIGN, SETTING, AND PARTICIPANTS: This is a single-institution retrospective study of 529 patients with biopsied solid SRMs ≤4 cm in diameter. RTBs were performed to aid in clinical management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Diagnostic and concordance rates were presented using proportions. Factors that contributed to a diagnostic biopsy were identified using a multivariable logistic regression. RESULTS AND LIMITATIONS: The first biopsy was diagnostic in 90% (n=476) of cases. Of the nondiagnostic biopsies, 24 patients underwent a second biopsy of which 83% were diagnostic. When both were combined, RTBs yielded an overall diagnostic rate of 94%. Following RTB, treatment could have been avoided in at least 26% of cases because the lesion was benign. Tumor size and exophytic location were significantly associated with biopsy outcome. RTB histology and nuclear grade were highly concordant with final pathology (93% and 94%, respectively). Adverse events were low (8.5%) and were all self-limited with the exception of one. Although excellent concordance between RTB and final pathology was observed, only a subset of patients underwent surgery following biopsy. Thus it is possible that some patients were misdiagnosed. CONCLUSIONS: RTB of SRMs provided a high rate of diagnostic accuracy, and more than a quarter were benign. Routine RTB for SRMs informs treatment decisions and diminishes unnecessary intervention. Our results support its systematic use and suggest that a change in clinical paradigm should be considered. PATIENT SUMMARY: Renal tumor biopsy (RTB) for pretreatment identification of the pathology of small renal masses (SRMs) is safe and reliable and decreases unnecessary treatment. Routine RTB should be considered in all patients with an indeterminate SRM for which treatment is being considered.

Progressive multifocal leukoencephalopathy in a 62-year-old immunocompetent woman.

Progressive multifocal encephalopathy (PML) is a rare demyelinating disease that typically presents in immunodeficient patients. We report a case of a previously healthy 62-Year-Old woman who suffered from an unsteady gait, throbbing headaches, and progressive left-sided weakness and numbness. Stroke was initially suspected based on imaging and symptoms. A series of follow-up magnetic resonance images of the brain showed a right parietal lesion growing in size as the patient became unable to walk and experienced increasing lethargy and confusion. A biopsy of the lesion was positive for the John Cunningham virus (JCV). A diagnosis of PML was made and she was started on mefloquine. No improvement was seen on this treatment and her condition worsened. Although PML remains uncommon in immunocompetent individuals, it cannot be ruled out based on their immune status. Although the exact cause remains uncertain, underlying or transient states of immunosuppression may be responsible for reactivation of the JCV in these patients.

Life-threatening hyperkalemia: a potentially lethal drug combination.

Hyperkalemia is commonly seen in the elderly and is occasionally fatal. Inadvertently combining potassium sparing medications can result in profound hyperkalemia which may result in cardiac dysrhythmias, especially in the setting of chronic kidney disease. An 85 year-old woman on a drug regimen of sotalol, valsartan, spironolactone, and trimethoprim-sulfamethoxazole presented to the emergency department with hypotension and bradycardia. Presumptive treatment for hyperkalemia was started based on her initial electrocardiogram. This diagnosis was later confirmed with a serum potassium value of 10.1 mmol/L. Following pharmacologic treatment, emergency hemodialysis was performed and the patient subsequently recovered. It is known that several drug classes can cause hyperkalemia, with elderly patients at a higher risk of developing this side effect. It is believed that this was a major contributor to the degree of hyperkalemia seen in this patient.

Survival following traumatic ventricular rupture and prolonged ambulance transport in a patient with previous coronary artery bypass surgery.

Patients presenting with traumatic cardiac rupture are unlikely to survive lengthy transfers from the trauma scene to a hospital. However, in patients with a previous sternotomy, adhesions may divert cardiac hemorrhage, allowing hemodynamic management to be successful. We present an 83-year-old male with a history of coronary artery bypass grafting (CABG) who sustained a right ventricular rupture. He underwent an immediate redo sternotomy and was discharged 10 days postoperatively with no complications.