Genomic Alterations of Signaling and DNA Damage Repair Pathways in Non-Muscle Invasive Bladder Cancer.

The aim of the study was to demonstrate the most common genetic alterations and evaluate possible targets involving phosphatidylinositol-3-OH kinase (PIK3)/AKT/mammalian target of rapamycin (mTOR) signaling and DNA damage repair (DDR) pathways for personalized treatment in patients with non-muscle invasive bladder cancer (NMIBC). Alterations of these pathways were observed in 89.5% and 100% of patients, respectively. Among them, BARD1 was more frequently altered in low/intermediate-risk cases, but PARP4 was more frequently affected in intermediate/high-risk patients. The possible target feasibility of BARD1 and PARP4 alterations should be evaluated for personalized treatment using PARP-inhibitors in NMIBC. It is important to detect high tumor mutation burden (TMB) in patients in terms of immunotherapy.

Anna Karenina principle in personalized treatment of bladder cancer according to oncogram: which drug for which patient?

Aim: To evaluate the ex vivo efficacy of chemotherapy, immunotherapy and targeted agents with the oncogram method in patients with bladder cancer and determine the most appropriate personalized treatment agent using immune markers. Materials & methods: Bladder cancer tissues were obtained from each patient. After cultivation, cell cultures were divided into 12 groups for each patient and 11 drugs were administered. Cell viability and immunohistochemistry expression were examined. Results: A good response rate was determined to be a 23% viability drop. The nivolumab good response rate was slightly better in PD-L1-positive patients and the ipilimumab good response rate was slightly better in tumoral CTLA-4-positive cases. Interestingly, the cetuximab response was worse in EGFR-positive cases. Conclusion: Although good responses of drug groups after their ex vivo application by using oncogram were found to be higher than control group, this outcome differed on a per patient basis.

Bladder cancer primary cell cultures were shown to be effective for drug sensitivity and also able to be used ex vivo in the process of determining personalized treatment. The ex vivo efficacy of 11 different agents was evaluated with oncogram in bladder cancer cell cultures obtained from patients. Together with clinicopathological features, evaluation of drug responses detected by oncogram can provide important information for pretreatment drug selection when deciding on individualized treatment.

Assessments of ReDo buccal mucosal urethroplasty in terms of functional outcomes.

PURPOSE: We aimed to assess the success rates and functional outcomes of ReDo buccal mucosal graft urethroplasty (BMGU) following failed primary BMGU and evaluate the oral morbidity and changes in quality of life (QoL) after this surgery. MATERIALS AND METHODS: Data of the patients with recurrent anterior urethral stricture who underwent ReDo BMGU after failed primary BMGU were retrospectively reviewed. The collected data included the results of the urethral stricture surgery patient-reported outcome measure-lower urinary tract symptoms (USS-PROM-LUTS) and euro-quality of life visual analog scale (EQ-VAS) questionnaires performed preoperatively before and one year after surgery. The cohort was divided into two groups according to procedural success, and these groups were compared. RESULTS: Thirty-two men patients were included. Among these, twenty-seven (84.3%) cases were considered successful following ReDo BMGU. The pre-ReDo BMGU mean stricture length was significantly longer in the failure group (2.3 ± 0.6 vs. 4.4 ± 1.2 cm, p = 0.001). Except for one patient with persistent oral numbness, no severe complication was reported postoperatively in the first year. The mean USS-PROM-LUTS score decreased significantly, while the mean LUTS-related quality of life score increased significantly following ReDo BMGU (p < 0.001, p < 0.001). In addition, the mean total EQ-VAS score increased significantly from 62.75 to 78.45, indicating remarkable improvement (p < 0.001). CONCLUSIONS: Although less favorable outcomes can be anticipated in ReDo BMGU due to extensive scar tissue formation and reduced vascularity, high success and patient satisfaction rates and low oral morbidity rates were detected in ReDo BMGU cases.

A candidate antineoplastic herbal agent for bladder cancer: Ankaferd Blood Stopper.

BACKGROUND AND AIMS: Ankaferd Blood Stopper (ABS) was used for in vitro studies of osteosarcoma and colon carcinoma cancer cell lines to reveal the apoptotic and antineoplastic effects. The aim of this study is to evaluate the antineoplastic effect of ABS on bladder cancer cell cultures. METHODS: We prospectively collected minimum 0.5 cm parts of fresh frozen tumour samples from patients with bladder tumour from 2015 to 2017. Primary bladder cancer cultures were produced from the frozen tumour samples. Two different doses of ABS were used on cancer cell cultures. Viability tests of each cell cultures were performed. Flow cytometry was used for the determination of apoptosis and necroptosis. We also checked the effect of ABS on different stages, grade and variant histology of bladder cancer cells. The results of all cancer cell cultures were compared with their own controls. RESULTS: This study included 24 patients. Mean age of patients was 66.2 ± 11.7 years (34-83 years), where 19 of them (79.5%) were males and five (20.5%) were females. When we compared the data, we found decreased cancer cell viability ratio in each ABS group compared with their own controls. Necroptosis was observed in the great majority of ABS groups, and necroptosis and apoptosis were observed in some cell cultures. CONCLUSIONS: In this study, we demonstrated the cytotoxic effect of ABS on bladder cancer cells. The results of this study suggests planning of animal model of bladder cancer for ABS with intravesical application as an antineoplastic agent. In the future, ABS may be a candidate intravesical treatment agent for bladder cancer.

Can we perform frozen section instead of repeat transurethral resection in bladder cancer?

OBJECTIVE: To confirm frozen section (FS) method for muscularis propria (MP) sampling and to compare the FS method with the ReTUR section (RS) procedure to reduce needing for second resection that can cause waste of time for definitive treatment of muscle-invasive bladder cancer. METHODS: A total of 27 patients who admitted to our clinic and was performed transurethral resection of bladder tumor (TUR-BT) due to bladder tumor and had an indication of ReTUR were evaluated prospectively in the study. During the first TUR-BT procedure (as permanent section), FS examination was also performed to the patients. ReTUR was performed 2-6 weeks after the first TUR-BT procedure. RESULTS: Presences of MP were observed in 51.8% and 77.7% of FS and permanent section examinations. In the comparing of the presence of residual tumor in the methods, although 12 of 27 patients were found to have a residual tumor in FS, it was found to be in only 6 of 12 patients in RS. There was no statistical significance between FS and RS methods for MP sampling and detecting of residual tumor. CONCLUSIONS: FS was found to be a comparable method with the RS method (ReTUR procedure) for the sampling of MP and detecting of residual tumor, despite the limitations in the pathological examination FS. Especially in patients with detected residual tumor after the pathological consultation of FS during the procedure, re-resection can be a choice at the end of the first TUR-BT instead of ReTUR.

Assessment of ex-vivo efficacy (oncogram) of immunotherapeutic and chemotherapeutic agents in bladder cancer: A pilot study of personalized treatment.

PURPOSE: To investigate the ex-vivo efficacy of immunotherapeutics and chemotherapeutics in bladder cancer primary cell cultures, to assess the applicability of the method according to the results and to evaluate suitability of the oncogram method for personalized treatment of bladder cancer. METHODS: After receiving ethics committee approval, tumor tissue was obtained from patients with transurethral resection performed due to bladder tumor from 2015 to 2017. Primary culture was produced from the obtained fresh tissue. Each culture was divided into 6 groups. The control group had only medium applied, while the other groups had Bacillus Calmette Guerin (BCG), Interferon-α (IFN-α), Gemcitabine, BCG+IFN-α and BCG+Gemcitabine, respectively. Viability tests in the 24th hour were performed on each culture. The results of all cases were compared with their own controls. Also, results of each case were compared between the cases with similar pathologic results. RESULTS: The study assessed 24 bladder cancer cases. Mean patient age was 66.2±11.7 years (34-83), with 19 male (79.5%) and 5 female patients (20.5%). When data were compared between the groups, viability percentages were 31.2%, 30.9%, 27.7%, 32.1% and 29.4% in the BCG, IFN-α, Gemcitabine, BCG+IFN-α and BCG+Gemcitabine groups compared with their own controls (73.1%), respectively (p<0.001). In addition, we found that viability results were not similar in all cases. CONCLUSIONS: Cell cultures produced from bladder cancer tissue might help to determine sensitivity to treatment. This ex-vivo method (oncogram) is a simple and applicable method that can be used for personalized treatment before intravesical or systemic therapy.