Introduction: Histopathology can provide insights into disease mechanism, but to date has been poorly described in urethral strictures. The purpose of this study was to comprehensively describe the histopathologic findings from stricture specimens obtained at the time of anterior urethroplasty (AU). Methods: All pathologic specimens from men undergoing AU for USD from 2010-2017 at a single institution were re-reviewed by a single, blinded pathologist who was directed to rule out lichen sclerosus (LS) and then describe inflammatory cell type and severity when present. Cohorts comprised of strictures with no inflammation, minimal to mild inflammation, or moderate to severe inflammation were developed and stricture, patient and surgical outcome characteristics were compared. Results: Histopathology slides from 100 AU cases were reviewed. Two or more LS characteristics were present in 21% of specimens and 44% of specimens showed chronic inflammation (minimal 20%, mild 39%; moderate 39%; severe 2%). Lymphocytes (86%) and plasma cells (12%) were the predominant cell type. Patients with inflammatory strictures reported worse overall health. Inflammation was largely absent from isolated bulbomembranous strictures (9%) and more common in LS strictures (100%). The overall failure rate of 11% was not affected by the presence (7%) or absence (14%) of inflammation. Conclusions: Chronic inflammation is prevalent in a significant percentage of USD specimens. Associations with worse overall health suggest systemic mediators. Absence of inflammation in bulbomembranous strictures suggests a unique pathophysiology in this region. The presence of inflammation did not affect surgical outcomes at medium-term follow-up.

Benign Prostatic Hyperplasia / Lower Urinary Tract Dysfunction (BPH/LUTD) is a classic disease of aging which affects nearly all men. Symptoms typically present in the fifth or sixth decade and progressively worsen over the remainder of life. Here, we identify a surprising origin of this disease that traces back to the intrauterine environment of the developing male, challenging existing paradigms about when this disease process begins. We delivered a single bolus dose of a widespread environmental contaminant, present in the serum of most Americans (2,3,7,8 tetrachlorodibenzo-p-dioxin, TCDD, 1 µg/kg), and representative of a broader class of environmental contaminants, to pregnant mice and observed an increase in the abundance of a neurotrophic factor, artemin, in the developing mouse prostate. Artemin is required for noradrenergic axon recruitment across multiple tissues and TCDD rapidly increases prostatic noradrenergic axon density in the male fetus. The hyperinnervation does not resolve, but rather persists into adulthood, when it is coupled to autonomic hyperactivity of prostatic smooth muscle and abnormal urinary function, including increased urinary frequency, a bothersome symptom in men. We offer new evidence that prostate neuroanatomical development is malleable and that intrauterine chemical exposures can permanently reprogram prostate neuromuscular function to cause male LUTD in adulthood.

ObjectiveTo assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m 2 ) is associated with peri-operative outcomes, overall survival (OS), cancer-specific survival (CSS), or recurrencefree survival (RFS) after surgical treatment for renal cell carcinoma (RCC). Patients and MethodsAfter institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan-Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables. ResultsIn all, 100 patients (11.9%) with a BMI ≥ 40 kg/m 2 and 743 patients (88.1%) with a BMI < 40 kg/m 2 who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587-1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3-6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30-day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m 2 was not a predictor of major complications (OR 0.58, 95% CI 0.227-1.47; P = 0.251) or 90-day mortality (P = 0.4067). BMI ≥ 40 kg/m 2 was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m 2 was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5-year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/ m 2 and BMI ≥ 40 kg/m 2 , respectively (P = 0.69). The 5-year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m 2 and BMI ≥ 40 kg/m 2 , respectively. The 5-year RFS rates for BMI < 40 kg/m 2 and BMI ≥ 40 kg/m 2 were 84.1 and 90.6%, respectively (P = 0.48). ConclusionsExtreme obesity is not associated with worse peri-operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients.

We used male BTBR mice carrying the Lepob mutation, which are subject to severe and progressive obesity and diabetes beginning at 6 weeks of age, to examine the influence of one specific manifestation of sleep apnea, intermittent hypoxia, on male urinary voiding physiology and genitourinary anatomy. A custom device was used to deliver continuous normoxia (NX, control) or intermittent hypoxia (IH) to wild type and Lepob/ob (mutant) mice for 2 weeks. Intermittent hypoxia was delivered during the 12-hour inactive (lighted) period in the form of 90 sec of 6% O2 followed by 90 sec of room air. Continuous room air was delivered during the 12-hour active (dark) period. We then evaluated genitourinary anatomy and physiology. As expected for the type 2 diabetes phenotype, mutant mice consume more food and water, weighed more, and voided more frequently and in larger urine volumes. They also have larger bladder volumes but smaller prostates, seminal vesicles, and urethras than wild type mice. IH decreases food consumption and increases bladder relative weight independent of genotype and increases urine glucose concentration in mutant mice. When evaluated based on genotype (NX+IH), the incidence of pathogenic bacteriuria is greater in mutant than wild type mice, and among mice exposed to IH, bacteriuria incidence is greater in mutant than wild type mice. We conclude that IH exposure and type 2 diabetes can act independently and together to modify male mouse urinary function.

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