Purpose: Although neoadjuvant chemotherapy is associated with a survival advantage in pure urothelial, muscle invasive bladder cancer, the role of neoadjuvant chemotherapy is less clear in variant histology or urothelial carcinoma with divergent differentiation. We compared chemotherapy response and survival outcomes of patients with nonpure urothelial carcinoma histology who were managed with neoadjuvant chemotherapy followed by cystectomy vs cystectomy alone. Materials and Methods:We analyzed 768 patients with clinical muscle invasive bladder cancer (cT2-4N0M0) who were treated with cystectomy at a tertiary care center from 2007 to 2017. Patients were stratified by histology and treatment strategy. Adjusted logistic and Cox regression models were used to evaluate pathological downstaging, cancer specific survival and overall survival. Results:The cohort consisted of 410 patients (53%) with pure urothelial carcinoma, 185 (24%) with urothelial carcinoma with divergent differentiation and 173 (23%) with variant histology. Overall, 314 patients (41%) received neoadjuvant chemotherapy prior to cystectomy. There were similar rates of complete (18% to 30%) and partial (37% to 46%) pathological downstaging with neoadjuvant chemotherapy across all histological subgroups (p=0.30 and p=0.40, respectively). However, while patients with pure urothelial carcinoma experienced an overall survival benefit (HR 0.71, 95% CI 0.51-0.98, p=0.0013) and those with variant histology experienced a cancer specific survival benefit (HR 0.55, 95% CI 0.30-0.99, p=0.0495) with neoadjuvant chemotherapy, patients with urothelial carcinoma with divergent differentiation did not experience overall or cancer specific survival benefits with the use of neoadjuvant chemotherapy prior to cystectomy.

Summary A clearer understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal cell carcinoma (ccRCC) may help to inform precision treatment strategies. We sought to identify clinically meaningful TIME signatures in ccRCC. We studied tumors from 39 patients with metastatic ccRCC using quantitative multiplexed immunofluorescence and relevant immune marker panels. Cell densities were analyzed in three regions of interest (ROIs): tumor core, tumor–stroma interface and stroma. Patients were stratified into low‐ and high‐marker density groups using median values as thresholds. Log‐rank and Cox regression analyses while controlling for clinical variables were used to compare survival outcomes to patterns of immune cell distributions. There were significant associations with increased macrophage (CD68+CD163+CD206+) density and poor outcomes across multiple ROIs in primary and metastatic tumors. In primary tumors, T‐bet+ T helper type 1 (Th1) cell density was highest at the tumor–stromal interface (P = 0·0021), and increased co‐expression of CD3 and T‐bet was associated with improved overall survival (P = 0·015) and survival after immunotherapy (P = 0·014). In metastatic tumor samples, decreased forkhead box protein 3 (FoxP3)+ T regulatory cell density correlated with improved survival after immunotherapy (P = 0·016). Increased macrophage markers and decreased Th1 T cell markers within the TIME correlated with poor overall survival and treatment outcomes. Immune markers such as FoxP3 showed consistent levels across the TIME, whereas others, such as T‐bet, demonstrated significant variance across the distinct ROIs. These findings suggest that TIME profiling outside the tumor core may identify clinically relevant associations for patients with metastatic ccRCC.

Although AAST-OIS is strongly associated with the need for urological intervention, perinephric hematoma size is also independently associated with this occurrence. Perinephric hematoma diameter should be considered during clinical decision making and incorporated into a revised injury grading system.

Introduction: Contemporary Canadian renal trauma data is lacking. Our objective is to describe 10-year outcomes of renal trauma at a Canadian level 1 trauma centre using a conservative approach. Methods: The Alberta Trauma Registry at the University of Alberta was used to identify renal trauma patients from October 2004 to December 2014. Hospital records and imaging were reviewed to identify clinic-radiographical factors, including patient age, gender, Injury Severity Score (ISS), American Association of the Surgery for Trauma (AAST) grade, computerized tomography (CT) findings, urological interventions, length of stay, transfusion and death rates. Descriptive statistics, Chi-square, and t-tests were used when appropriate. Results: A total of 368 renal trauma patients were identified. Mechanism of injury was blunt trauma in 89.1% of cases, mean age was 36.2 years, and mean ISS was 30.8 (±13.6). AAST grade distribution was 16.6% (Grade 1), 22.8% (Grade 2), 36.4% (Grade 3), 20.9% (Grade 4), and 3.3% (Grade 5). Overall, 9.5% (35) of patients required urological intervention for a total of 40 treatments, including ureteral stenting (3.0%), angioembolization (3.3%), percutaneous drainage (0.3%), or open intervention including nephrectomy (2.4%) and renorrhaphy (0.5%). No Grade 1 or 2 injuries required intervention, while 1.5%, 31.2%, and 75.0% of Grade 3, 4, and 5 injuries did, respectively. The overall renal salvage rate was 97.6%, which did not differ by mechanism of injury (p=0.25). Patients with penetrating trauma were more likely to require urological intervention (20.0% vs. 8.2%; p=0.04). Of the high-grade (III–V) renal injuries identified, 15.7% (35/223) required urological intervention, 4.9% (11) required open surgical intervention, and only 4.0% (9) of patients with high-grade renal injury required nephrectomy. Conclusions: The trend towards conservative treatment of renal trauma in Canada appears well-supported even in a severely injured patient population, as over 90% of patients avoid urological intervention and only 3% require operative intervention resulting in renal salvage rates of 97.6%.

Introduction: The artificial urinary sphincter (AUS) is the most effective treatment option for incontinence after prostate cancer treatment. However, patients with a “fragile urethra” (defined as prior radiotherapy, previous failed AUS, or previous urethroplasty) are at increased risk of AUS failure. The aim of this study was to evaluate outcomes using standard and transcorporal cuff placement in this group of patients. Methods: A retrospective review was performed on patients with a fragile urethra who underwent AUS insertion between 2004 and 2017. The primary outcome was the need for AUS revision. Secondary outcome measures included change in pad use, patient satisfaction, continence (≤1 pad/day), improvement (≥50% change in pad use) and cuff erosion rates. Results: Seventy-six patients met the criteria for inclusion, with a mean age of 71.6 years and a mean followup of 37.9 months. A total of 42.1% had prior radiotherapy, 56.6% had a history of failed AUS, and 19.7% had previous urethroplasty. Transcorporal cuff placement was performed in 31.6% (n=24). These patients had lower revision (20.8% vs. 36.5%; p=0.05) and erosion rates (8.3% vs. 17.3%; p=0.09). There was no significant difference in functional outcomes such as continence (66.7% vs. 73.1%; p=0.57), improvement (100% vs. 90.4%;p=0.17), or satisfaction (82.6% vs. 69.4%; p=0.26), nor for 90-day complications (4.2% vs. 9.6%; p=0.41). Conclusions: AUS insertion is an effective treatment option for post-prostatectomy incontinence in the setting of a fragile urethra. Transcorporal cuff placement in this subset of patients may be recommended, as it is associated with lower revision and erosion rates compared to standard cuff placement.