Implications of targeted next-generation sequencing for bladder cancer: report of four cases.

BACKGROUND: Bladder cancer is considered heterogeneous diseases with two major subgroups: non-muscle- invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). It is a major healthcare problem, and it is one of the leading causes of mortality worldwide. Genetic mutations are not only a cause for carcinogenesis but are also a way for treatment strategy. The present study aimed to investigate breast cancer (BRCA genes) tumor suppressor gene mutations in bladder cancer tissue and combined blood samples for patients who developed secondary tumor after or during trimodal therapy. Fresh tissue samples and their matched blood samples were collected from four patients with bladder cancer. The objective regions for the examined genes (BRCA1 and BRCA2) were sequenced using next-generation sequencing (NGS); generated BAM files were uploaded to the cloud-based Ionreporter server, and the Oncomine BRCA-specific plugin was used to analyze the paired normal and tumor sample for each patient using the default plugin parameters. RESULTS: Intronic BRCA1 mutation c.5050-104 C >T was reported among the four investigated bladder cancer patients, and three somatic mutations were reported as follows: two of them were found to be benign rs1064793056 and rs28897679 on the Clinivar database and one nonsense pathogenic variant rs80357006. BRCA 2 gene mutation reported an exonic synonymous mutation rs397507876 in the tissue and germline DNA. Patients were treated with trimodal; however, three bladder cancer patients who reported BRCA mutations developed secondary tumors. CONCLUSION: Identification of mutational BRCA changes in bladder cancer is a promising marker for better treatment strategy. Further studies are encouraged on a large cohort of bladder cancer patients to confirm our findings.

Apparent Diffusion Coefficient Value can Predict Poor Bacillus Calmette-Guérin Responders in T1HG/NMIBC: Prospective Cohort Study.

BACKGROUND: Prediction of recurrence and progression and the choice of type of management are largely based on stage and grade; however, these prognostic features are limited in the prediction of clinical outcomes. The objective was to investigate the relation between the apparent diffusion coefficient (ADC) value and recurrence and progression of T1G3 of urothelial carcinoma after transurethral resection of the bladder tumor (TURBT) and Bacillus Calmette-Guérin instillation. MATERIALS AND METHODS: This prospective study included 65 patients with single bladder mass T1G3 less than 3 cm without carcinoma in situ or lymphovascular invasion. Mean ADC values of the tumors were compared between patients with and without recurrence and progression following TURBT. The relation of ADC value and other factors were determined by univariate and multivariate analyses. The following tests were used to test differences for significance: difference and association of qualitative variable by χ2 test; differences between quantitative independent groups by t-test or Mann-Whitney U test; survival by Kaplan-Meier; Cox regression (or Cox proportional hazards model) was used to analyze the effect of several risk factors on time until event (recurrence and progression); correlation by Pearson or Spearman, and we calculated the most suitable cutoff and validity by receiver operating characteristic curve. RESULTS: In relation to recurrence, smoking, nonpapillary shape and higher size, and lower ADC were significant predictors for recurrence. In relation to progression, female sex, nonpapillary shape, and lower ADC were significant predictors for progression. Multivariate analysis showed that ADC < 1.09 was the only significant independent predictors for recurrence. Also, it showed that ADC < 0.98 was the only significant independent predictors for progression. CONCLUSION: Low ADC value group of T1G3 bladder cancer showed significant recurrence and progression than high ADC value group of T1G3 bladder cancer. ADC value in conjunction with other risk stratifications will have a promising role in stratifying patients with T1G3 who need to proceed to early radical cystectomy versus conservative treatment.

Outcomes of Flank-Free Modified Supine Percutaneous Nephrolithotomy Based on BMI.

OBJECTIVE: To evaluate the impact of body mass index (BMI) on the outcomes of percutaneous nephrolithotomy (PCNL) in the flank-free modified supine position. PATIENTS AND METHODS: A prospective study was carried out in the urology department during the period from May 2015 to October 2019 on 464 patients admitted for PCNL. The patients were divided into 4 matched groups according to their BMI: group A, normal weight with 18.5 ≤ BMI <25 kg/m2; group B, overweight with 25 ≤ BMI <30 kg/m2; group C, obese with 30 ≤ BMI <40 kg/m2; and group D, morbid obesity with BMI ≥40 kg/m2. All operative data as well as postoperative outcomes are recorded and compared to each other. RESULTS: The 4 studied groups were matched regarding age. The comorbidities were slightly higher in groups C and D. The operative time and fluoroscopy time were slightly high in obese and morbid obese groups but with no significant difference. The rate of complications either major or minor was comparable in all groups. No significant difference was seen among all groups regarding hemoglobin loss, stone-free rate, hospital stay, and need for auxiliary procedures. CONCLUSIONS: The outcome of PCNL in flank-free modified supine position is not affected by changes in BMI. The procedure can be performed in obese and morbid obese patients safely with results similar to and comparable to nonobese patients.

W-pouch With Modified Non-isolated Extra Limb for Continence in Cutaneous Diversion After Radical Cystectomy.

OBJECTIVE: To report the functional results of continent cutaneous ileal urinary diversion using modified W-pouch with non-isolated extra limb for continence. PATIENTS AND METHODS: From January 2013 to January 2016, 21 patients with muscle-invasive bladder cancer with median (interquartile range) of 59 (56.5-62.5) years old underwent radical cystectomy with pelvic lymphadenectomy; they then had an ileal continent cutaneous pouch constructed from W-pouch with non-isolated extra limb for continence. The technique entails the creation of a detubularized ileal W-pouch with extra limb fashioned from 59 cm of the terminal ileum. This extra limb is not isolated from the pouch. The proximal part of this limb is tailored and fixed in a subserous extramural tunnel for continence, whereas the distal part is left continuous with the pouch. The median (interquartile range) of follow up was 12 (8-17) months. Evaluation of the technique included operative time, continence efficiency, overall complications, and quality of life questionnaire for the patients. RESULTS: The median (interquartile range) of operative time of the operation was 4.7 (3.9-5.4) hours. The median (interquartile range) of operative time of the cutaneous pouch creation was 39 (33-43) minutes. No perioperative mortality had occurred. The incidence of continence was 95.2%. The overall complications were 42.8%, and most of them were grade 1 or 2 on Clavien-Dindo classification system. CONCLUSION: Modification of W-pouch with non-isolated extra limb as continent cutaneous pouch can simplify the technique and shorten the operative time with efficient continence, less side effects, and good quality of life.