Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

INTRODUCTION/PURPOSE: Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. MATERIALS/METHODS: Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. RESULTS: Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. CONCLUSIONS: All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

Elevated periprostatic venous testosterone correlates with prostate cancer progression after radical prostatectomy.

BACKGROUNDGenerally, clinical assessment of gonadal testosterone (T) in human physiology is determined using concentrations measured in peripheral blood. Prostatic T exposure is similarly thought to be determined from peripheral T exposure. Despite the fact that androgens drive prostate cancer, peripheral T has had no role in the clinical evaluation or treatment of men with localized prostate cancer.METHODSTo assess the role of local androgen delivery in prostate cancer, we obtained blood from the (periprostatic) prostatic dorsal venous complex in 266 men undergoing radical prostatectomy from July 2014 to August 2021 and compared dorsal T (DT) levels with those in circulating peripheral blood (PT) and prostatic tissue. Comprehensive targeted steroid analysis and unbiased metabolomics analyses were performed. The association between the DT/PT ratio and progression-free survival after prostatectomy was assessed.RESULTSSurprisingly, in some men, DT levels were enriched several-fold compared with PT levels. For example, 20% of men had local T concentrations that were at least 2-fold higher than peripheral T concentrations. Isocaproic acid, a byproduct of androgen biosynthesis, and 17-OH-progesterone, a marker of intratesticular T, were also enriched in the dorsal vein of these men, consistent with testicular shunting. Men with enriched DT had higher rates of prostate cancer recurrence. DT/PT concentration ratios predicted worse outcomes even when accounting for known clinical predictors.CONCLUSIONSThese data suggest that a large proportion of men have a previously unappreciated exposure to an undiluted and highly concentrated T supply. Elevated periprostatic T exposure was associated with worse clinical outcomes after radical prostatectomy.FUNDINGNational Cancer Institute (NCI), NIH grants R01CA172382, R01CA236780, R01CA261995, R01CA249279, and R50CA251961; US Army Medical Research and Development Command grants W81XWH2010137 and W81XWH-22-1-0082.

Microbe-metabolite interaction networks, antibiotic resistance, and in vitro reconstitution of the penile prosthesis biofilm support a paradigm shift from infection to colonization.

To understand differences between asymptomatic colonized and infected states of indwelling medical devices, we sought to determine penile prosthesis biofilm composition, microbe-metabolite interaction networks, and association with clinical factors. Patients scheduled for penile prosthesis removal/revision were included. Samples from swabbed devices and controls underwent next-generation sequencing, metabolomics, and culture-based assessments. Biofilm formation from device isolates was reconstituted in a continuous-flow stir tank bioreactor. 93% of 27 analyzed devices harbored demonstrable biofilm. Seven genera including Faecalibaculum and Jeotgalicoccus were more abundant in infected than uninfected device biofilms (p < 0.001). Smokers and those with diabetes mellitus or cardiac disease had lower total normalized microbial counts than those without the conditions (p < 0.001). We identified microbe-metabolite interaction networks enriched in devices explanted for infection and pain. Biofilm formation was recapitulated on medical device materials including silicone, PTFE, polyurethane, and titanium in vitro to facilitate further mechanistic studies. Nearly all penile prosthesis devices harbor biofilms. Staphylococcus and Escherichia, the most common causative organisms of prosthesis infection, had similar abundance irrespective of infection status. A series of other uncommon genera and metabolites were differentially abundant, suggesting a complex microbe-metabolite pattern-rather than a single organism-is responsible for the transition from asymptomatic to infected or painful states.

Ureteral Stents Harbor Complex Biofilms With Rich Microbiome-Metabolite Interactions.

PURPOSE: We sought to determine microbe-metabolite composition and interactions within indwelling ureteral stent biofilms, determine their association with patient factors including infection, and reconstitute biofilm formation on relevant surface materials in vitro. MATERIALS AND METHODS: Upon ureteral stent removal from patients, proximal and distal ends were swabbed. Samples were analyzed by 16S next-generation sequencing and metabolomics. A continuous-flow stir-tank bioreactor was used to reconstitute and quantify in vitro biofilm formation from stent-isolated bacteria on stent-related materials including silicone, polytetrafluoroethylene, polyurethane, polycarbonate, and titanium. Diversity, relative abundance, and association with clinical factors were analyzed with ANOVA and Bonferroni t-tests or PERMANOVA. Biofilm deposition by microbial strain and device material type were analyzed using plate counts and scanning electron microscopy following bioreactor incubation. RESULTS: All 73 samples from 37 ureteral stents harbored microbiota. Specific genera were more abundant in samples from stents wherein there was antibiotic exposure during indwelling time (Escherichia/Shigella, Pseudomonas, Staphylococcus, Ureaplasma) and in those associated with infection (Escherichia/Shigella, Ureaplasma). The enriched interaction subnetwork in stent-associated infection included Ureaplasma and metabolite 9-methyl-7-bromoeudistomin. Strains identified as clinically relevant and central to interaction networks all reconstituted biofilm in vitro, with differential formation by strain (Enterococcus faecalis most) and material type (titanium least). CONCLUSIONS: Ureteral stent biofilms exhibit patterns unique to stent-associated infection and antibiotic exposure during indwelling time. Microbes isolated from stents reconstituted biofilm formation in vitro. This work provides a platform to test novel materials, evaluate new coatings for anti-biofilm properties, and explore commensal strain use for bacterial interference against pathogens.

Cognitive impairment does not impact sacral neuromodulation implant rates for overactive bladder.

OBJECTIVE: To evaluate the impact of cognitive impairment (CI) diagnoses on sacral neuromodulation (SNM) outcomes in older patients. MATERIALS AND METHODS: We completed a retrospective review of all patients aged ≥55 years who underwent test-phase SNM (peripheral nerve evaluation (PNE) or stage 1) for overactive bladder (OAB) between 2014 and 2021 within a large multi-regional health system. Patient demographics, relevant comorbidities, CI diagnoses (dementia or mild CI), and SNM procedures were recorded. Logistic regression modeling was performed to evaluate the impact of CI on SNM implantation rates. RESULTS: Five-hundred and ten patients underwent SNM test phase (161 PNE, 349 Stage 1) during the study period. The mean age was 71.0(8.5) years, and most (80.6%) were female. Overall, 52(10.1%) patients had a CI diagnosis at the time of SNM, and 30 (5.8%) were diagnosed at a median of 18.5 [9.25, 39.5] months after SNM. Patients with CI diagnoses were older, with more comorbidities, and were more likely to undergo PNE. Univariable comparison found no difference in implantation rate based on pre-SNM CI (85.4% vs. 76.9%, p = 0.16). Multivariable analysis identified PNE (OR 0.43, 95% CI 0.26-0.71), age (OR 0.96, 95%CI 0.93-0.98), and prior beta-3 agonist use (OR 0.60, 95% CI 0.37-0.99) but not CI or dementia as independent negative predictors of implantation. Implanted patients had a median follow-up of 25 [12.0, 55.0] months. Explant and revision rates did not differ according to CI. CONCLUSION: Patients with OAB and CI diagnoses proceed to SNM implant at rates similar to patients without CI diagnoses. A diagnosis of CI should not necessarily exclude patients from SNM therapy for refractory OAB.

Biofilms on Indwelling Artificial Urinary Sphincter Devices Harbor Complex Microbe-Metabolite Interaction Networks and Reconstitute Differentially In Vitro by Material Type.

The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe−metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p < 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection.

Estimated Glomerular Filtration Rate Using Cystatin C is a More Sensitive Marker for Kidney Dysfunction in Nonweight-bearing Individuals.

PURPOSE: Individuals with neuromuscular disorders and neurogenic lower urinary tract dysfunction are commonly nonweight-bearing with lower lean muscle mass than the general population. We sought to compare estimated glomerular filtration rate equations that include creatinine, cystatin C, or both, in nonweight-bearing individuals and matched ambulatory controls. MATERIALS AND METHODS: Records were reviewed for individuals with serum creatinine (Cr) and cystatin C (Cys) and diagnosis consistent with nonweight-bearing status, and matched ambulatory controls. The 2021 CKD-EPI (Chronic Kidney Disease-Epidemiology Collaboration) race agnostic equations were used to calculate estimated glomerular filtration rate. Renal function was compared by equation in the overall cohorts and in a patient subset with imaging and/or urinalysis evidence of renal dysfunction. RESULTS: Nonweight-bearing (n = 102) and control populations (n = 204) had similar demographics. In the nonweight-bearing population, estimated glomerular filtration rate differed when calculated using CKD-EPICr, CKD-EPICr+Cys, and CKD-EPICys (107, 93, 80 mL/min/1.73 m2, respectively, P < .001). The differences in estimated glomerular filtration rate were greater in the nonweight-bearing relative to the control group regardless of CKD-EPI equation pairs compared (P < .001). In the patient subset with imaging and/or proteinuria evidence of renal dysfunction, the nonweight-bearing population again had different estimated glomerular filtration rate when calculated using CKD-EPICr, CKD-EPICr+Cys, and CKD-EPICys (P < .001). Fifty-eight percent of nonweight-bearing individuals with evidence of renal dysfunction on imaging or urinalysis were reclassified into a lower estimated glomerular filtration rate category when using estimated glomerular filtration rateCys relative to estimated glomerular filtration rateCr. CONCLUSIONS: Estimated glomerular filtration rate equations containing serum creatinine, cystatin C, or both, validated in mostly ambulatory populations, are not equivalently accurate in estimating kidney function in nonweight-bearing individuals. Comparison of these equations against gold standard glomerular filtration rate measurement is needed to determine which most closely approximates true glomerular filtration rate.

Analysis of Native Kidney Function Recovery With Renal Scintigraphy Following Simultaneous Liver-Kidney Transplantation.

BACKGROUND: Patients undergoing simultaneous liver-kidney transplantation (SLK) have impaired native kidney function. The relative contribution of allograft versus native function after SLK is unknown. We sought to characterize the return of native kidney function following SLK. METHODS: Following SLK, patients underwent technetium-99 m-mercaptoacetyltriglycine renal scintigraphy following serum creatinine nadir. Kidney contributions to estimated glomerular filtration rate (eGFR) were determined. Patients with native kidney function at serum creatinine nadir contributing eGFR ≥30 versus <30 mL/min/1.73 m 2 were compared, and multiple linear regression analysis for native eGFR improvement was performed. RESULTS: Thirty-one patients were included in this analysis. Average native kidney contribution to overall kidney function following SLK was 51.1% corresponding to native kidney eGFR of 44.5 mL/min/1.73 m 2 and native kidney function eGFR improvement of 30.3 mL/min/1.73 m 2 ( P < 0.001). Twenty-six of 31 patients had native kidney contribution of eGFR ≥30 mL/min/1.73 m 2 . Hepatorenal syndrome as the sole primary etiology of kidney dysfunction was 100% specific for native kidney eGFR >30 mL/min/1.73 m 2 and predicted native eGFR improvement ( P = 0.03). CONCLUSIONS: Substantial improvement in native kidney function follows SLK, and hepatorenal syndrome as the sole primary etiology of kidney dysfunction is predictive of improvement. Whether such patients are suitable for liver transplant followed by surveillance with option for subsequent kidney transplants requires investigation.

IsoPSA® Reduces Provider Recommendations for Biopsy and Magnetic Resonance Imaging in Men with Total Prostate Specific Antigen ≥4 ng/ml: A Real-World Observational Clinical Utility Study.

INTRODUCTION: We assessed the impact of the IsoPSA® test for prostate cancer risk assessment on provider patient management decisions in a real-world clinical setting. METHODS: A total of 38 providers, including advanced practice providers, fellowship trained oncologists and general urologists in the Cleveland Clinic health system including both community-based practices and academic locations, enrolled 900 men being evaluated for prostate cancer; 734 met inclusion criteria (age ≥50 years, total serum prostate specific antigen [PSA] ≥4 and <100 ng/ml and no history of prostate cancer) and IsoPSA indication for use. A standard template was used to document biopsy recommendation prior to and after receiving IsoPSA results. The primary outcome was the number of biopsy and magnetic resonance imaging recommendation changes occurring after IsoPSA testing. RESULTS: IsoPSA testing resulted in a 55% (284 vs 638) net reduction in recommendations for prostate biopsy for men with total PSA ≥4 ng/ml. Additionally, a 9% reduction in recommendations for magnetic resonance imaging was observed. There was strong concordance between IsoPSA results and provider recommendations for prostate biopsy, with 87% of patients with an IsoPSA index above the threshold recommended for biopsy and 92% of patients with an IsoPSA index below the threshold not recommended for biopsy. CONCLUSIONS: In a real-world clinical setting, providers from diverse training backgrounds and practice settings readily adopted IsoPSA with substantial reductions in the rate of recommended prostate biopsies in patients with elevated PSA values (≥4 ng/ml). There was a high concordance between recommendation for or against prostate biopsy and the IsoPSA result.

Older Age at Diagnosis and Initial Disease Volume Predict Grade Reclassification Risk on Confirmatory Biopsy in Patients Considered for Active Surveillance.

OBJECTIVE: To identify which active surveillance candidates benefit most from confirmatory biopsies to exclude grade underclassification. MATERIALS AND METHODS: This observational study includes 556 men diagnosed between 2002 and 2015 with Gleason 3 + 3 (GG1) disease on initial diagnostic biopsy, of whom 406 received a confirmatory biopsy within 12 months for active surveillance. Multivariable logistic regression analysis was performed to determine clinicopathologic features associated with Gleason 7 or higher (GG2+) on a confirmatory biopsy. Regression tree analysis was employed to stratify patients into select risk groups. RESULTS: Eighty-five of 406 patients (20.9%) with initially GG1 disease were reclassified to GG2+ on a confirmatory biopsy. On multivariable analysis, increasing age (per year odds ratio 1.07; 95% confidence interval 1.02-1.12; P <.01) and more positive cores at diagnosis (per core, odds ratio 1.37, 95% confidence interval 1.09-1.72; P <.01) were significantly associated with reclassification, independent of prostate volume, clinical stage, initial PSA, or confirmatory biopsy type (including magnetic resonance imaging-targeted approaches or transrectal saturation random sampling). Recursive partitioning demonstrated that age over 73 and 5 or more positive cores were factors associated with the greatest reclassification risk. CONCLUSION: In our cohort, both advancing age and additional positive cores were associated with increased odds of reclassification to GG2+ on confirmatory biopsy. In men over age 73 or with 5 or more positive cores, a repeat biopsy within 12 months may be particularly beneficial to minimize tumor grade underclassification.

Lost in transition: Patient-identified barriers to adult urological spina bifida care.

INTRODUCTION: It has been established that patients with congenital diseases, including spina bifida (SB) are often lost to routine medical care in young adulthood. While the reasons for this observation are not entirely defined, many believe it is multifactorial. OBJECTIVE: This study sought to characterize self-reported barriers to transition among adults with SB who failed to transition to adult urological care. STUDY DESIGN: This study, conducted at two tertiary centers with established adult myelomeningocele multidisciplinary clinics, enrolled patients with SB who had not been seen in >18 months. A visit was scheduled and upon arrival patients were provided a questionnaire with 22 yes/no questions about barriers to arranging a visit and eight questions regarding their health issues. Questions were categorized as relating to patient factors, provider factors, and system factors. To facilitate targeted areas of improvement, patient factors were further subdivided into self-management/support (SMS), preferences, and education, and provider factors into knowledge, communication, and location. System factors included only questions related to insurance issues. The questionnaire was uncomplicated, which eliminated the need for assistance when answering the questions. RESULTS: There were 27 questionnaires collected. Overall, a total of seven patients (26%) identified no barriers to follow-up, eight identified one barrier (30%), and 12 (44%) identified more than one barrier. Patient factors made up approximately 52% (28 of 54 total "Yes" responses) of all barriers, with Preference being the largest contributor (30%, 16/54) (Fig.). Provider factors accounted for about 37% (20/54) of all barriers, with the Communication (26%, 14/54) subcategory making up the vast majority. System factors contributed only 11% (6/54) of all barriers. The majority of patients (18/27, 67%) reported having a new health issue since their last visit to their pediatric urologist, with only five of 18 (28%) seeking urological care. DISCUSSION: This study demonstrated that the decision to pursue adult urologic care is multifactorial. The questionnaire may not have captured all of the reasons SB patients are lost to follow-up, as a quarter of patients did not identify a barrier. Limitations of this study include the small number of participants, use of only two study locations, and the closed-ended nature of the questionnaire. CONCLUSION: Multiple factors contribute to the SB patient's decision to pursue adult urologic care. Targeted areas of improvement include provider communication at both the pediatric and adult level, as well as education regarding patient preferences and SMS.

AR Signaling in Prostate Cancer Regulates a Feed-Forward Mechanism of Androgen Synthesis by Way of HSD3B1 Upregulation.

3ßHSD1 enzymatic activity is essential for synthesis of potent androgens from adrenal precursor steroids in prostate cancer. A germline variant in HSD3B1, the gene that encodes 3ßHSD1, encodes for a stable enzyme, regulates adrenal androgen dependence, and is a predictive biomarker of poor clinical outcomes after gonadal testosterone deprivation therapy. However, little is known about HSD3B1 transcriptional regulation. Generally, it is thought that intratumoral androgen synthesis is upregulated after gonadal testosterone deprivation, enabling development of castration-resistant prostate cancer. Given its critical role in extragonadal androgen synthesis, we sought to directly interrogate the transcriptional regulation of HSD3B1 in multiple metastatic prostate cancer cell models. Surprisingly, we found that VCaP, CWR22Rv1, LNCaP, and LAPC4 models demonstrate induction of HSD3B1 upon androgen stimulation for approximately 72 hours, followed by attenuation around 120 hours. 3ßHSD1 protein levels mirrored transcriptional changes in models harboring variant (LNCaP) and wild-type (LAPC4) HSD3B1, and in these models androgen induction of HSD3B1 is abrogated via enzalutamide treatment. Androgen treatment increased flux from [3H]-dehydroepiandrosterone to androstenedione and other downstream metabolites. HSD3B1 expression was reduced 72 hours after castration in the VCaP xenograft mouse model, suggesting androgen receptor (AR) regulation of HSD3B1 also occurs in vivo. Overall, these data suggest that HSD3B1 is unexpectedly positively regulated by androgens and ARs. These data may have implications for the development of treatment strategies tailored to HSD3B1 genotype status.

Impact of 5α-Reductase Inhibitors on Disease Reclassification among Men on Active Surveillance for Localized Prostate Cancer with Favorable Features.

PURPOSE: We determined the effect of 5α-reductase inhibitors on disease reclassification in men with prostate cancer optimally selected for active surveillance. MATERIALS AND METHODS: In this retrospective review we identified 635 patients on active surveillance between 2002 and 2015. Patients with favorable cancer features on repeat biopsy, defined as absent Gleason upgrading, were included in the cohort. Patients were stratified by those who did or did not receive finasteride or dutasteride within 1 year of diagnosis. The primary end point was grade reclassification, defined as any increase in Gleason score or predominant Gleason pattern on subsequent biopsy. This was assessed by multivariable Cox proportional hazards regression analysis. RESULTS: At diagnosis 371 patients met study inclusion criteria, of whom 70 (19%) were started on 5α-reductase inhibitors within 12 months. Median time on active surveillance was 53 vs 35 months in men on vs not on 5α-reductase inhibitors (p <0.01). Men on 5α-reductase inhibitors received them for a median of 23 months (IQR 6-37). On actuarial analysis there was no significant difference in grade reclassification for 5α-reductase inhibitor use in patients overall or in the very low/low risk subset. The overall percent of patients who experienced grade reclassification was similar at 13% vs 14% (p = 0.75). After adjusting for baseline clinicopathological features 5α-reductase inhibitors were not significantly associated with grade reclassification (HR 0.80, 95% CI 0.31-1.80, p = 0.62). Furthermore, no difference in adverse features on radical prostatectomy specimens was observed in treated patients (p = 0.36). CONCLUSIONS: Among our cohort of men on active surveillance 5α-reductase inhibitor use was not associated with a significant difference in grade reclassification with time.

HSD3B1 status as a biomarker of androgen deprivation resistance and implications for prostate cancer.

Patients with advanced prostate cancer who receive androgen deprivation therapy (ADT) almost invariably develop castration-resistant disease. The mechanism of resistance is largely based on synthesis of intratumoral androgens from adrenal precursors, requiring enzymatic action of 3ß-hydroxysteroid dehydrogenase/Δ5→4 isomerase 1 (3ß-HSD1), encoded by HSD3B1. A nucleotide polymorphism (1245A>C) in HSD3B1 results in a protein variant with increased steady-state levels and subsequently increased androgen synthesis from extragonadal precursors. Multiple clinical studies have shown that patients with the variant allele have significantly worse outcomes after ADT than those without, indicating that HSD3B1 variant status is a predictive biomarker of shortened ADT response. In addition, inheritance of the HSD3B1 variant is associated with extended responses to 17α-hydroxylase/17,20-lyase (CYP17A1) inhibition with a nonsteroidal agent, adding to evidence of increased tumour dependence on extragonadal androgens in patients who inherited the HSD3B1 variant. However, steroidal drugs with a 3ß-hydroxyl, Δ5-structure, such as abiraterone, are also metabolized by 3ß-HSD1, and 5α-abiraterone, a downstream metabolite, has been shown to activate the androgen receptor, potentially driving cancer progression. These data indicate a potential requirement to modify the treatment framework of patients harbouring variant HSD3B1.

Prognostic Significance of a Negative Confirmatory Biopsy on Reclassification Among Men on Active Surveillance.

OBJECTIVE: To examine the association between absence of disease on confirmatory biopsy and risk of pathologic reclassification in men on active surveillance (AS). MATERIALS AND METHODS: Men with grade groups 1 and 2 disease on AS between 2002 and 2015 were identified who received a confirmatory biopsy within 1 year of diagnosis and ≥3 biopsies overall. The primary outcomes were pathologic reclassification by grade (any increase in primary Gleason pattern or Gleason score) or volume (>33% of sampled cores involved or increase in the number of cores with >50% involvement). The effect of a negative confirmatory biopsy survival was evaluated using Kaplan-Meier analysis and a Cox proportional hazards modeling. RESULTS: Out of 635 men, 224 met inclusion criteria (median follow-up: 55.8 months). A total of 111 men (49.6%) had a negative confirmatory biopsy. Decreased grade reclassification (69.7% vs 83.9%; P = .01) and volume reclassification (66.3% vs 87.4%; P = .004) was seen at 5 years for men with a negative confirmatory biopsy compared with those with a positive biopsy. On adjusted analysis, a negative confirmatory biopsy was associated with a decreased risk of grade reclassification (hazard ratio, 0.51; 95% confidence interval, 0.28-0.94; P = .03) and volume reclassification (hazard ratio, 0.32; 95% confidence interval, 0.17-0.61; P = .0006) at a median of 4.7 years. CONCLUSION: Absence of cancer on the confirmatory biopsy is associated with a significant decrease in rate of grade and volume reclassification among men on AS. This information may be used to better counsel men on AS.

Do Routine Preoperative and Intraoperative Urine Cultures Benefit Pediatric Vesicoureteral Reflux Surgery?

Objective. To determine if routine preoperative and intraoperative urine cultures (UCx) are necessary in pediatric vesicoureteral (VUR) reflux surgery by identifying their association with each other, preoperative symptoms, and surgical outcomes. Materials and Methods. A retrospective review of patients undergoing ureteral reimplant(s) for primary VUR at a tertiary academic medical center between years 2000 and 2014 was done. Preoperative UCx were defined as those within 30 days before surgery. A positive culture was defined as >50,000 colony forming units of a single organism. Results. A total of 185 patients were identified and 87/185 (47.0%) met inclusion criteria. Of those, 39/87 (45%) completed a preoperative UCx. Only 3/39 (8%) preoperative cultures returned positive, and all of those patients were preoperatively symptomatic. No preoperatively asymptomatic patients had positive preoperative cultures. Intraoperative cultures were obtained in 21/87 (24.1%) patients; all were negative. No associations were found between preoperative culture results and intraoperative cultures or between culture result and postoperative complications. Conclusions. In asymptomatic patients, no associations were found between the completion of a preoperative or intraoperative UCx and surgical outcomes, suggesting that not all patients may require preoperative screening. Children presenting with symptoms of urinary tract infection (UTI) prior to ureteral reimplantation may benefit from preoperative UCx.

Intermediate-Term Outcomes for Men with Very Low/Low and Intermediate/High Risk Prostate Cancer Managed by Active Surveillance.

PURPOSE: We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance. MATERIALS AND METHODS: A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.5 months (IQR 31.1-80.3). Time to event analysis was performed for our clinical end points. RESULTS: Of the cohort 117 men (18.4%) had intermediate/high risk disease. Overall 5 and 10-year all cause survival was 98% and 94%, respectively. Cumulative metastasis-free survival at 5 and 10 years was 99% and 98%, respectively. To date no cancer specific deaths had been observed. Overall freedom from intervention was 61% and 49% at 5 and 10 years, respectively. Overall cumulative freedom from failure of active surveillance, defined as metastasis or biochemical failure after local therapy with curative intent, was 97% and 91% at 5 and 10 years, respectively. Of the men 21 (9.9%) experienced biochemical failure after deferred treatment and the 5-year progression-free probability was 92%. Compared to men with favorable risk disease those with intermediate/high risk cancer experienced no difference in metastases, surveillance failure or curative intervention. However, patients at higher risk were at significantly increased risk for all cause mortality, likely reflecting patient selection factors. These conclusions may be limited by the small number of events and the duration of our study. CONCLUSIONS: Patients with localized prostate cancer who are on active surveillance demonstrated a low rate of active surveillance failure, prostate cancer specific mortality and metastases regardless of baseline risk.