Mohamed Gad

Background and Objectives: Pathological upstaging from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) at radical cystectomy (RC) compromises preoperative risk stratification and may deprive patients of the survival benefit conferred by neoadjuvant chemotherapy. This study aimed to define the frequency and independent predictors of pathological upstaging in a contemporary single-institution cohort, and to characterise its impact on recurrence-free, disease-specific, and overall survival. Materials and Methods: We conducted a retrospective review of a prospectively maintained database of all patients who underwent RC and pelvic lymphadenectomy for urothelial bladder cancer at our institution between January 2009 and December 2023. Upstaging was defined as the final pathological stage ≥ pT2 or pN+ from a clinical stage of p = 0.042), variant histology—predominantly squamous differentiation (p = 0.003)—and urethral involvement (p = 0.003) as independent predictors of upstaging. Upstaged patients had significantly worse 5-year RFS (p < 0.001), DSS (p = 0.01), and OS (p < 0.001) compared with patients who remained NMIBC. No statistically significant difference in survival was observed between patients upstaged at RC and those presenting with primary MIBC. Conclusions: Pathological upstaging occurs in more than a quarter of patients undergoing RC for NMIBC and confers a survival penalty equivalent to that of primary MIBC. Concomitant CIS, variant histology, and urethral involvement identify those at highest risk. These patients warrant aggressive preoperative counselling, expedited surgical planning, and consideration of perioperative systemic therapy.

Introduction: Conservative or upfront radical management for high- and very high-risk non-muscle-invasive bladder cancer continues to be debated, particularly for cases with adverse pathological features. We aimed to compare survival outcomes among NMIBC patients treated with transurethral resection of bladder tumour (TURBT) followed by either Bacillus Calmette–Guérin (BCG), sequential BCG plus electromotive administration of mitomycin C (EMDA-MMC), or upfront radical cystectomy (RC). Materials and Methods: High- and- very high-risk NMIBC cases undergoing TURBT followed by BCG, BCG plus EMDA-MMC, or RC at two international tertiary referral centres between 2009 and 2024 were retrospectively reviewed. Recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier methods. Multivariable Cox regression models were applied to identify factors independently associated with survival outcomes. Results: A total of 1178 patients were included: 852 received BCG, 249 received BCG/EMDA-MMC, and 77 underwent upfront RC. Kaplan–Meier analysis revealed no significant differences in RFS or PFS between the BCG and BCG/EMDA-MMC groups, nor in OS between the three treatment strategies. According to multivariable analysis, concomitant carcinoma in situ (CIS) and increasing T stage at TURBT were independently associated with poorer RFS (HR 1.39; 95% CI 1.05–1.85), PFS (HR 1.95; 95% CI 1.36–2.82), and OS (HR 2.28; 95% CI 1.60–3.25). A second resection conferred a protective effect on PFS (HR 0.72; 95% CI 0.54–0.95). Treatment modality (BCG, BCG/EMDA-MMC, or upfront RC) was not significantly associated with any survival endpoint. Conclusions: In this large multicentre series of patients with high- and very high-risk NMIBC undergoing TURBT, survival outcomes were primarily influenced by clinical–pathological characteristics rather than the adjuvant treatment of choice.

Background: Female patients undergoing radical cystectomy (RC) for bladder cancer have historically presented with more advanced disease and poorer survival outcomes than males. These disparities have been attributed to biological differences, delayed diagnosis, and variations in treatment delivery. Recent data suggest, however, that outcomes may converge when patients are managed in standardized, multidisciplinary, high-volume centers. This study evaluated the influence of gender on perioperative features and oncological outcomes such as disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) at a tertiary uro-oncology center. Methods: We retrospectively reviewed a prospectively maintained database of patients who underwent open or robotic-assisted RC for histologically confirmed urothelial carcinoma between 2014 and 2023 at Guy’s and St. Thomas’ NHS Foundation Trust. Demographic, perioperative, and pathological variables were stratified by gender to assess their association with DFS, DSS, and OS. Results: A total of 887 patients were included: 640 men (72.2%) and 247 women (27.8%), with similar mean age (68.5 vs. 68.1 years) and tumour histology (pure urothelial carcinoma 85% vs. 83%). Men had a higher prevalence of diabetes and chronic kidney disease, but no significant differences were observed in time from referral to surgery (0.93 vs. 1.03 months, p = 0.93), use of neoadjuvant therapy (21.6% vs. 17.3%, p = 0.25), or surgical approach (p = 0.55). Pathological stage distribution was comparable between sexes (pT0–1: 44% vs. 50%; pT2–4: 56% vs. 50%; p = 0.13). Kaplan–Meier analysis revealed no significant gender-related differences in 12-month DFS (77.3% vs. 75.4%, p = 0.20), DSS (85.6% vs. 86.9%, p = 0.56), or OS (81.2% vs. 85.2%, p = 0.70). Conclusion: In this high-volume tertiary center, gender did not independently influence perioperative or survival outcomes following radical cystectomy. These findings suggest that standardized, multidisciplinary management within specialized bladder cancer pathways may mitigate the pathological and survival disparities historically associated with gender.

Klinefelter syndrome (KS) is the most common genetic cause of male infertility, affecting approximately 1 in 660 men. It is characterized by the presence of one or more extra X chromosomes. Literature suggests an increased risk of venous thromboembolic events (VTE) in KS. Testosterone replacement therapies (TRT) are commonly used in KS to improving well-being, body composition and sexual function. However, TRT may influence the risk of VTE. Our objective was to assess the rate of VTE, and its association with TRT, in a cohort of KS patients. Data on VTE, TRT usage, and demographics were obtained from a hospital-based KS clinic database. 179 patients were included. The median age was 35 years (interquartile range [IQR] 29-42 years). 118 (66%) had received TRT prior to the review in clinic. 11 patients (6.1%) had at least one VTE. The median age of first VTE was 35 years (range 19-73 years). The incidence of a VTE was 17.0 (95% confidence interval [CI] 8.5-30.3) events per 10,000 person-years. Five of the 11 patients had received TRT prior to VTE. There was no significant association between receiving TRT and suffering a VTE (p=0.1). The incidence rate of VTE in KS patients observed here is approximately four-fold higher than in the general adult male population. This is consistent with previous studies that have showed an increase rate ratio of between 2.1 and 12.1, dependent on age. This study did not show a statistically significant difference in VTE incidence based on the use of TRT.

The choice of ureteral access sheath (UAS) size in flexible ureteroscopy (fURS) is pivotal in balancing endoscopic performance with ureteral safety. Larger sheaths (12/14 Fr) provide superior irrigation flow and intrarenal pressure control but raise concerns regarding ureteral trauma, particularly in unstented ureters. This PRISMA-aligned systematic review (January 2010-August 2025) synthesizes the available evidence comparing 10/12 Fr and 12/14 Fr UAS, both standard and suction-enabled, in terms of pressure modulation, irrigation efficiency, thermal regulation, ureteral injury, stricture formation, and infectious outcomes. Emerging data show that suction-assisted 12/14 Fr sheaths significantly lower rates of postoperative fever and sepsis without increasing ureteral injury when applied judiciously. Pre-stenting remains a key strategy for minimizing insertion-related trauma. The findings highlight an evolving clinical paradigm in UAS selection: shifting from a purely size-based choice to a physiology-driven approach that optimizes safety, visibility, and procedural efficiency.