RESULTS• The AR were positively expressed in 61/ 472 (12.9%) bladder tumours. No statistically significant difference in AR expression between men and women was observed.• Only 9.0% of non-muscle-invasive BC expressed the AR compared with 15.1% of muscle-invasive tumours ( P = 0.059). The highest percentage of AR positivity (28.9% of cases) was found in T2 tumours.• There was no statistically significant difference in death from BC, time to death, or time to recurrence between AR-positive and AR-negative cases. CONCLUSION• In contrast to previous reports, based on our large BC series, we did not observe a decrease in AR protein expression in bladder tumours with increased pathological stage. Our data do not suggest that loss of AR expression is gender-related nor is it associated with invasive BC. KEYWORDS Androgen receptor, bladder cancer, immunohistochemistry, tissue microarrays Study Type -Prognosis (multi-centre cohort) Level of Evidence 1bWhat's known on the subject? and What does the study add? More men than women develop bladder cancer (BC) but reasons why are unclear. Recent findings have implicated androgens, androgen receptors (AR) and AR expression in BC. Previous studies showed that a significant loss of AR expression was associated with aggressive BC. However, these results have been gathered on limited series of patients.We analyzed the expression of AR in BC and its correlation with gender, grade, stage and clinical outcome on a large multi-institutional (Toronto/Dallas) cohort. In contrast to previous reports, our data do not suggest that loss of AR expression is gender-related nor associated with invasive BC. In fact, in this large cohort, we showed that AR positivity is actually uncommon in BC, that there are no differences in expression among high and low grade tumours and no statistically significant differences between muscle-invasive ARpositive and AR-negative cases in time to death, or time to recurrence. OBJECTIVE• To investigate androgen receptor (AR) expression in a large series of patients with bladder cancer (BC) because data on a limited number of patients showed that loss of AR expression was associated with invasive BC. PATIENTS AND METHODS• A total of 472 patients with urothelial bladder carcinoma (UBC) from two institutional centres (Toronto and Dallas) were analysed. Tissue microarrays comprising both non-muscle-invasive UBC ( n = 167) and muscle-invasive UBC ( n = 305) were accrued and immunohistochemical staining for AR was performed.• We used bright-field microscopy imaging coupled with advanced colour detection software to detect, classify and count stained cellular objects and manual scoring.• Results obtained in Dallas were blindly reviewed and validated in Toronto and samples randomly chosen were further analysed in Rochester, NY, USA.

In this series the overall complication rate was similar for tubularized incised plate and onlay urethroplasty. Despite similar urethroplasty calibers, the uroflow curves and fistula positions in patients undergoing tubularized incised plate repair suggest that the neourethra distal to the fistula may be relatively narrow, creating flow resistance and leading to proximal fistula. Longer followup and close monitoring are needed before embracing one approach over the other.

Objective To characterize risk of hypotension requiring admission to hospital in middle aged and older men treated with tamsulosin for benign prostatic hyperplasia.Design Population based retrospective cohort study (between patient methodology) and self controlled case series (within patient methodology).Setting Healthcare claims data from the IMS Lifelink database in the United States.Participants Men aged 40-85 years with private US healthcare insurance entering the cohort at their first dispensing for tamsulosin or for a 5α reductase inhibitor (5ARI) between January 2001 and June 2011after a minimum of six months' enrolment. Main outcomes measures Hypotension requiring admission to hospital.Cox proportional hazards models estimated rate ratios at time varying intervals during follow-up: weeks 1-4, 5-8, and 9-12 after tamsulosin initiation; weeks 1-4, 5-8, and 9-12 after restarting tamsulosin (after a four week gap); and maintenance tamsulosin treatment (remaining exposed person time). Covariates included age, calendar year, demographics, antihypertensive use, healthcare use, and a Charlson comorbidity score. A self controlled case series, having implicit control for time invariant covariates, was additionally conducted.Results Among 383 567 new users of study drugs (tamsulosin 297 596; 5ARI 85 971), 2562 admissions to hospital for severe hypotension were identified. The incidence for hypotension was higher for tamsulosin (42.4 events per 10 000 person years) than for 5ARIs (31.3 events per 10 000 person years) or all accrued person time (29.1 events per 10 000 person years). After tamsulosin initiation, the cohort analysis identified an increased rate of hypotension during weeks 1-4 (rate ratio 2.12 (95% confidence interval 1.29 to 3.04)) and 5-8 (1.51 (1.04 to 2.18)), and no significant increase at weeks 9-12. The rate ratio for hypotension also increased at weeks 1-4 (1.84 (1.46 to 2.33)) and 5-8 (1.85 (1.45 to 2.36)) after restarting tamsulosin, as did maintenance tamsulosin treatment (1.19 (1.07 to 1.32)). The self controlled case series gave similar results as the cohort analysis. ConclusionsWe observed a temporal association between tamsulosin use for benign prostatic hyperplasia and severe hypotension during the first eight weeks after initiating treatment and the first eight weeks after restarting treatment. This association suggests that physicians should focus on improving counseling strategies to warn patients regarding the "first dose phenomenon" with tamsulosin.