Cell therapy constitutes an attractive alternative to treat stress urinary incontinence. Although promising results have been demonstrated in this field, the procedure requires further optimization. The most commonly proposed cell types for intraurethral injections are muscle derived cells (MDCs) and mesenchymal stem/stromal cell (MSCs). The aim of this study was to evaluate the effects of MDC-MSC co-transplantation into the urethra. Autologous transplantation of labeled MDCs, bone marrow MSCs or co-transplantation of MDC-MSC were performed in aged multiparous female goats (n = 6 in each group). The mean number of cells injected per animal was 29.6 × 106(± 4.3 × 106). PBS-injected animals constituted the control group (n = 5). Each animal underwent urethral pressure profile (UPP) measurements before and after the injection procedure. The maximal urethral closure pressure (MUCP) and functional area (FA) of UPPs were calculated. The urethras were collected at the 28th or the 84th day after transplantation. The marker fluorochrome (DID) was visualized and quantified using in vivo imaging system in whole explants. Myogenic differentiation of the graft was immunohistochemically evaluated. The grafted cells were identified in all urethras collected at day 28 regardless of injected cell type. At this time point the strongest DID-derived signal (normalized to the number of injected cells) was noted in the co-transplanted group. There was a distinct decline in signal intensity between day 28 and day 84 in all types of transplantation. Both MSCs and MDCs contributed to striated muscle formation if transplanted directly to the external urethral sphincter. In the MSC group those events were rare. If cells were injected into the submucosal region they remained undifferentiated usually packed in clearly distinguishable depots. The mean increase in MUCP after transplantation in comparison to the pre-transplantation state in the MDC, MSC and MDC-MSC groups was 12.3% (± 11.2%, not significant (ns)), 8.2% (± 9.6%, ns) and 24.1% (± 3.1%, p = 0.02), respectively. The mean increase in FA after transplantation in the MDC, MSC and MDC-MSC groups amounted to 17.8% (± 15.4%, ns), 15.2% (± 12.9%, ns) and 17.8% (± 2.5%, p = 0.04), respectively. The results suggest that MDC-MSC co-transplantation provides a greater chance of improvement in urethral closure than transplantation of each population alone.
15 January 2018 in World Journal of Surgical Oncology
Indications for restaging transurethral resection of the bladder tumor (reTURBT) in patients with non-muscle-invasive bladder cancer (NMIBC) remain controversial. This study was aimed at evaluation of clinical value and safety of reTURBT in different clinical indications. This is a retrospective analysis of consecutive 141 patients who underwent TURBT followed by reTURBT in years 2011–2015 in a single department. Pathological results and surgical complications were analyzed in the whole study cohort and stratified by clinical stage (Ta, T1, Tx (no muscle in the specimen)) and grade (low-grade (LG), high-grade (HG)) of bladder cancer diagnosed at primary TURBT. Full data was available for 132 patients. Residual disease was found in 53 patients (40.2%) with highest rate for Ta-HG cases (57.1%) followed by T1-HG (51.4%), Tx-HG (45.2%), T1-LG (32.1%), and Tx-LG (25.8%). In the multivariate analysis, high grade (p = 0.02) was the only independent predictor of residual disease. Upstaging to muscle-invasive bladder cancer was noticed in 9 patients (6.8%). The rate of grade ≥ 2 Clavien-Dindo complications (1.5 vs. 5.3%) did not differ significantly between TURBT and reTURBT cases. ReTURBT is a safe procedure that remains crucial for therapeutic and staging purposes in patients with T1, Tx, or high-grade bladder cancer found in the primary resection.
Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy in bladder cancer patients with asymptomatic bacteriuria (ABU) remains a matter of debate. The aim of this systematic review was to present available evidence on the safety and efficacy of BCG immunotherapy in patients with ABU. A literature search within the Medline and the Embase databases was conducted with the following search terms: adverse events, bacteriuria, BCG, bladder cancer, cystitis, infection, pyuria, side effects and urinary tract infection (UTI). Sixteen relevant original articles were identified, including 6 articles directly presenting the safety or efficacy of BCG therapy in patients with ABU. None of them was a randomized controlled trial. Intravesical BCG instillations in patients with ABU were not associated with the increased risk of symptomatic UTI and did not affect negatively the recurrence- or progression-free survival. Routine urine analysis before BCG instillation created increased cost and potentially unnecessary delays in BCG therapy. ABU does not affect negatively the safety and efficacy of intravesical BCG immunotherapy. There is no evidence to support routine screening and treatment of ABU in patients scheduled for intravesical BCG instillations due to bladder cancer. However, this issue was not addressed adequately and needs further research.
The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events with specific implications. We aimed to evaluate the accuracy of available risk models and identify additional risk factors for HG RFS and PFS among NMIBC patients treated with Bacillus Calmette–Guérin (BCG). We retrospectively included 171 patients who underwent transurethral resection of the bladder tumor (TURBT), of whom 73 patients (42.7%) experienced recurrence and 29 (17%) developed progression. Initially, there were 21 low-grade and 52 high-grade recurrences. EORTC2006, EORTC2016 and CUETO recurrence scoring systems lacked accuracy in the prediction of HG RFS (C-index 0.63/0.55/0.59, respectively). EAU2021 risk stratification, EORTC2006, EORTC2016, and CUETO progression scoring systems demonstrated low to moderate accuracy (C-index 0.59/0.68/0.65/0.65) in the prediction of PFS. In the multivariable analysis, T1HG at repeat TURBT (HR = 3.17 p < 0.01), tumor multiplicity (HR = 2.07 p < 0.05), previous history of HG NMIBC (HR = 2.37 p = 0.06) and EORTC2006 progression risk score (HR = 1.1 p < 0.01) were independent predictors for HG RFS. To conclude, available risk models lack accuracy in predicting HG RFS and PFS in -NMIBC patients treated with BCG.
Up-to-date studies emphasize the role of human urinary and intestinal microbiome in maintaining urogenital health. Both microbial flora and sexually transmitted pathogens may affect metabolic or immune mechanisms and consequently promote or inhibit prostate carcinogenesis. Hereby, we review the most current evidence regarding the microbial factors and their link to prostate cancer. We conducted a literature search up to December 2020. The microbial impact on prostate cancer initiation and progression is complex. The proposed mechanisms of action include induction of chronic inflammatory microenvironment (Propionibacterium spp., sexually-transmitted pathogens) and direct dysregulation of cell cycle (Helicobacter pylori, Kaposi’s sarcoma-associated herpesvirus- KSHV, human papilloma virus 18- HPV18). Suppression of immune cell expression and downregulating immune-associated genes are also observed (Gardnerella vaginalis). Additionally, the impact of the gut microbiome proved relevant in promoting tumorigenesis (Bacteroides massiliensis). Nevertheless, certain microbes appear to possess anti-tumor properties (Listeria monocytogenes, Pseudomonas spp.), such as triggering a robust immune response and apoptotic cancer cell death. The role of microbial factors in prostate cancer development is an emerging field that merits further studies. In the future, translating microbial research into clinical action may prove helpful in predicting diagnosis and potential outcomes of the disease.