Predicting individual outcomes after radical cystectomy in urothelial variants with Cancer of the Bladder Risk Assessment (COBRA) score.

OBJECTIVE: To validate the Cancer of the Bladder Risk Assessment (COBRA) score in patients with urothelial variants. METHODS: Epidemiological, clinical, radiological, and anatomopathological data were collected from patients with urothelial carcinoma who underwent radical cystectomy at the Institute of Cancer of São Paulo between May 2008 and December 2022. Patients with the presence of at least 10% of any urothelial variants in the radical cystectomy specimens' anatomopathological exam were included in the study. The COBRA score and derivatives were applied and correlated with oncological outcomes. RESULTS: A total of 680 patients [482 men (70.9%) and 198 women (29.1%)]; 66 years (IQR 59-73) underwent radical cystectomy for bladder tumor, and of these patients, a total of 167 patients presented any type of urothelial variant. The median follow-up time was 28.77 months (IQR 12-85). The three most prevalent UV were squamous differentiation (50.8%), glandular differentiation (31.3%), and micropapillary differentiation (11.3%). The subtypes with the worst prognosis were sarcomatoid with a median survival of 8 months (HR 1.161; 95% CI 0.555-2.432) and plasmacytoid with 14 months (HR 1.466; 95% CI 0.528-4.070). The COBRA score for patients with micropapillary variants demonstrated good predictive accuracy for OS (log-rank P = 0.009; 95% IC 6.78-29.21) and CSS (log-rank P = 0.002; 95% IC 13.06-26.93). CONCLUSIONS: In our study, the COBRA score proved an effective risk stratification tool for urothelial histological variants, especially for the micropapillary urothelial variant. It may be helpful in the prognosis evaluation of UV patients after radical cystectomy.

Transvaginal ultrasonography for trigonitis diagnosis in women.

OBJECTIVE: Chronic trigonitis (CT) is usually diagnosed through cystoscopy which is invasive and expensive. Thus, an accurate non-invasive diagnostic method is necessary. The objective of this study is to determine the efficacy of transvaginal bladder ultrasound (TBU) for CT diagnosis. METHODS: Between 2012 and 2021, 114 women (17-76 years old) with recurrent urinary tract infection (RUTI) and history of antibiotic resistance were evaluated with TBU by a single ultrasonographer. As a control group, TBU was performed in 25 age-matched women with no previous history of UTI, urological or gynecological conditions. All patients with RUTI had undergone a cystoscopy with biopsy for diagnostic confirmation at the time of trigone cauterization. RESULTS: Thickening of trigone mucosa (>3 mm) was detected in all patients with RUTI and represented the most relevant criteria for trigonitis diagnosis on TBU. Other TBU findings in CT are: irregular and interrupted mucosa lining (96.4%), free debris in the urine (85.9%), increased blood flow at doppler (81.5%), mucosa shedding and tissue flaps. Biopsy showed CT with erosive pattern (58%) or non-keratinizing metaplasia (42%). Diagnostic agreement index between TBU and cystoscopy was 100%. In the control group, normal trigone mucosa is ultrasonographically regular, continuous, with thickness ≤3 mm and there is no debris in the urine. CONCLUSIONS: TBU proved to be an efficient, inexpensive and minimally invasive method to diagnose CT. To our knowledge, this is the first article that reports the use of transvaginal ultrasound as an alternative method for diagnosing trigonitis.

Scoring system for prediction of overall survival in patients with renal cell carcinoma T3aN0M0.

Objective: We aim to create a new score to predict postoperative overall survival in patients with nonmetastatic T3aN0 renal cell carcinoma. Methods: We reviewed the clinical data of adult patients who underwent radical nephrectomy for renal cell carcinoma between December 2007 and January 2022 in a single tertiary oncological institution. Clinical characteristics, clinical-pathological staging and histopathological characteristics were analysed. Survival analyses were determined using the Kaplan-Meier curve. A nomogram was established using Cox proportional hazard regression to identify the prognostic factors affecting the overall survival. The area under the curve, calibration curves and decision curve analysis were used to evaluate prognostic efficacy. Results: We analyzed 362 patients classified as pT3aN0M0 stage with a median follow-up of 40 months. According to Cox univariate and multivariate analyses, weight loss greater than 5% in 6 months before surgery, stage V chronic kidney disease after radical nephrectomy, sarcomatoid pattern, and coagulative tumor necrosis were identified as predictors of overall survival. We developed a score and performed internal and external validation. The time-dependent receiver operating characteristic curve, area under the curve value and calibration curve analysis showed good prediction ability of the score. The nomogram can effectively predict and stratify overall survival after radical nephrectomy in patients with pT3aN0M0 renal cell carcinoma. Conclusion: Patients with pT3aN0MO renal cell carcinoma exhibited different characteristics, and those with unfavourable characteristics deserve greater attention during follow-up. This nomogram provides an accurate prediction of overall survival after radical nephrectomy.

Robotic-assisted approaches to urachal carcinoma: A comprehensive systematic review of the safety and efficacy outcomes.

Introduction: Surgical intervention is the treatment of choice in patients with urachal carcinoma. Due to complications and to reduce hospital stay from open surgery, minimally invasive approaches are desirable. Nowadays, robotic-assisted surgery has become increasingly popular, and robot-assisted cystectomy can be performed in patients with urachal carcinoma with low complication rates. Methods: We performed a systematic review to search for studies that evaluated patients who underwent robotic-assisted surgery for urachal carcinoma. The outcomes of interest were the type of cystectomy performed, whether there was umbilicus resection, total operative time, console time, intraoperative complications, estimated blood loss, postoperative complications, time of hospitalisation, positive surgical margins and the presence of documented tumour recurrence. Results: In this study, we evaluated three cohorts comprising a total of 21 patients. The median follow-up period ranged from 8 to 40 months. Medium age was between 51 and 54 years, with a majority (63.1%) being male. One patient (5.2%) underwent a radical cystectomy, and 19 patients (94.7%) underwent to partial cystectomy. Umbilical resections were performed in all cases, and pelvic lymphadenectomy in 14 cases (73.6%). Recurrence occurred in three patients at a median of 17 months postoperation, two cases in the trocar insertion site. Additionally, there was one death, which was attributed to postoperative cardiovascular complications. Conclusion: Robotic-assisted partial cystectomy has a low incidence of adverse outcomes in patients with urachal carcinoma. Controlled studies, ideally randomised, are warranted to establish the comparative efficacy and safety of the robotic-assisted cystectomy approach relative to open surgery.

Artificial intelligence for predicting response to neoadjuvant chemotherapy for bladder cancer A comprehensive systematic review and meta-analysis.

INTRODUCTION: Neoadjuvant cisplatin-based combination chemotherapy (NAC) followed by radical cystectomy is the standard of care for cisplatin-fit patients harboring muscle-invasive bladder cancer (MIBC). Prediction of response to NAC is essential for clinical decision-making regarding alternatives in case of non-response, and bladder-sparing in case of complete response. This research aimed to assess the performance of machine learning in predicting therapeutic response following NAC treatment in patients with MIBC. METHODS: A systematic review adhering to the PRISMA guidelines was conducted until July 2023. The study integrated articles relating to artificial intelligence and NAC response in MIBC from various databases. The quality of articles was evaluated using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 (QUADAS-2). A meta-analysis was subsequently performed on selected studies to determine the sensitivity and specificity of machine learning algorithms in predicting NAC response. RESULTS: Of 655 articles identified, 12 studies comprising 1523 patients were included, and four studies were eligible for meta-analysis. The sensitivity and specificity of the studies were 0.62 (95% confidence interval [CI] 0.50-0.72) and 0.82 (95% CI 0.72-0.89), respectively, with a heterogeneity score (I2) of 38.5%. The machine learning algorithms used computed tomography, genetic, and anatomopathologic data as input and exhibited promising potential for predicting NAC response. CONCLUSIONS: Machine-learning algorithms, especially those using computed tomography, genetic, and pathologic data, demonstrate significant potential for predicting NAC response in MIBC. Standardization of methodologic data analysis and response criteria are needed as validation studies.

Holmium Laser Resection of Large Bladder Tumors: Technique Description, Feasibility, and Histopathological Quality Analysis.

BACKGROUND: The HoLERBT (Holmium Laser En-bloc Resection of Bladder Tumors) has emerged as an alternative to classical TURBT (Transurethral Resection of Bladder Tumor). Recent randomized trial and meta-analysis corroborate with the benefits in pathological analysis, perioperative and long-term oncological outcomes.1-3 However, the treatment of large tumors and the technique of extraction from the bladder is a problem to be overcome.1,4 OBJECTIVE: To describe the laser resection of bladder tumors and demonstrate the feasibility of this procedure even for large tumors throughout a series of cases. It is also discussed the quality of the histopathological analysis. METHODS: A series of 8 cases randomized selected to be the pilot for a trial comparing TURBT and HoLERBT in large tumors (>3 cm) in progress was analyzed (Brazilian Registry of Clinical Trials number RBR-67npwrk). The perioperative data and 1-year outcomes were assessed and the quality of histopathological analysis after morcellation was evaluated in terms of histopathology, grade, and stage. The entire procedure of one case is shown in a step-by-step video. RESULTS: The mean follow-up was 12.6 months. The mean age was 59.6 (42-85) years, and the mean tumor size was 4.7 (4-8) cm. All the resections were En-bloc. There were 2 cases of NMIBC, 4 cases of MIBC, 1 paraganglioma, and 1 adenocarcinoma. The histopathological analysis confirmed the presence of detrusor muscle layer and accurate diagnosis and staging in all cases (100%). There were no perioperative Clavien-Dindo > 1 complications, no blood transfusion, and no bladder perforations. The histopathology analysis reveals excellent quality without artifacts of fulguration. CONCLUSION: The holmium laser resection followed by morcellation of large bladder tumors is a feasible procedure. No complications occurred in our series of cases and all cases provided excellent material for histopathological analysis.

Association between integrin expression and prognosis in localized prostate cancer.

BACKGROUND: Integrins and other adhesion molecules are essential for maintaining the epithelial phenotype. Some studies have reported correlations between abnormalities in their expression and carcinogenesis, but their role in prostate cancer is unclear. Our aim was to study the expression profile of integrins in surgical specimens of prostate cancer and associate their expression patterns with patient outcomes. METHODS: We selected 111 patients with localized prostate cancer who had undergone radical prostatectomy. Of these patients, 60 had no tumor recurrence after a median follow-up of 123 months. Integrin expression was evaluated by immunohistochemistry in a tissue microarray containing two tumor samples per patient. A semiquantitative analysis was employed. We measured the association between the expression of eight integrins and tumor recurrence. RESULTS: Multivariate analysis showed that expression of alpha3 and alpha3beta1 was related to worse outcome. When alpha3 expression was strong and alpha3beta1 expression was positive, the odds of recurrence were 3.0- and 2.5-fold higher, respectively. Only 19% and 28% of patients were recurrence-free in a mean period of 123 months of follow up when their tumors showed strong alpha3 or positive alpha3beta1 immuno-expression, respectively. CONCLUSIONS: We have shown that the expression of integrin alpha3beta1 was independently associated with tumor recurrence after radical prostatectomy, suggesting that this integrin is a potential prognostic marker.

Evaluation of the expression of integrins and cell adhesion molecules through tissue microarray in lymph node metastases of prostate cancer.

BACKGROUND: Integrins and adhesion molecules are responsible for the maintenance of the epithelial phenotype. Cell culture studies have reported the correlation between adhesion molecule expression and prostate carcinoma, but their role in the metastatic process is not yet known. Our aim is to study the expression profiles of these molecules and evaluate their association with the metastatic behavior of prostate adenocarcinoma. MATERIALS AND METHODS: A Tissue Microarray containing two samples from 19 primary tumors and one from their corresponding lymph node metastases was constructed and subjected to immunohistochemical analysis of the expression of integrins, E-cadherin and beta and gamma-catenins. Within each case, paired analyses were also performed to evaluate gains or losses in metastasis compared to its primary tumor. RESULTS: The expression of av, alphavbeta 3, alpha2beta 1 and gamma-catenin were abnormal in almost every case. Marked loss of E-cadherin and beta 4 integrin was found in primary and metastatic lesions. beta -catenin was normal in all primary cases and in 94% of metastases. a6 was normal in all primary tumors and metastases. alpha3 and alpha3beta 1 were normal in 32% of primary cases and in 53% and 6% of metastases, respectively. In paired analyses, loss of E-cadherin, beta 4, alphav, alpha3beta 1 and alphavbeta 3 was found in 65%, 71%, 59%, 53% and 47% of patients, respectively. Catenins and alpha2beta 1 showed maintenance of expression in most of the cases. CONCLUSIONS: In this preliminary study we have shown that the loss of cell adhesion molecules can be considered a characteristic of the metastatic phenotype in prostate cancer. Larger series should be evaluated in order to confirm our findings.

Acellular matrix in urethral reconstruction.

The treatment of severe urethral stenosis has always been a challenge even for skilled urologists. Classic urethroplasty, skin flaps and buccal mucosa grafting may not be used for long and complex strictures. In the quest for an ideal urethral substitute, acellular scaffolds have demonstrated the ability to induce tissue regeneration layer by layer. After several experimental studies, the use of acellular matrices for urethral reconstruction has become a clinical reality over the last decade. In this review we analyze advantages and limitations of both biological and polymeric scaffolds that have been reported in experimental and human studies. Important aspects such as graft extension, surgical technique and cell-seeding versus cell-free grafts will be discussed.

Evaluation of the incidence of bladder perforation after transurethral bladder tumor resection in a residency setting.

PURPOSE: To evaluate prospectively the actual bladder perforation incidence during transurethral resection of bladder tumor (TURB) performed by residents and to identify possible predisposing factors to such condition. PATIENTS AND METHODS: Thirty-four patients with bladder tumor were submitted to TURB in our academic institution in April 2006, and were prospectively studied. Procedures were all done by senior residents under an attending direct supervision. All patients had a cystograms performed after the procedure by the injection of 400 mL of saline-diluted contrast solution with low-pressure infusion through the Foley catheter. The cystograms were evaluated blindly by a single radiologist. All patients were examined by cystoscopy and/or CT every 3 months for the first 2 years postoperatively. RESULTS: The cystogram showed contrast leaking compatible with bladder perforation in 17 (50%) cases. None of the perforations were recognized intraoperatively by the surgeon. All perforations were extraperitoneal and managed conservatively. There was no significant correlation between the incidence of bladder perforation and the patient age (p = 0.508), the tumor stage (p = 0.998), the tumor grade (p = 0.833), the number of lesions (p = 0.394), and the tumor size (p = 0.651). The only factor that had impact on the development of bladder perforation was tumor localization at the bottom of the bladder (p = 0.035; OR, 6750; 95% CI, 1.14, 39.8). CONCLUSION: Asymptomatic perforations of the bladder wall occur very frequently after a TURB procedure performed by residents in training and, most of the time, are not noticed by the surgeon. Localization of the tumor at bladder dome was the only factor that negatively influenced perforation rates.

Microvascular tumor invasion, tumor size and Fuhrman grade: a pathological triad for prognostic evaluation of renal cell carcinoma.

PURPOSE: The biological behavior and clinical outcome of renal cell carcinoma are difficult to predict. We investigated the prognostic impact of clinicopathological variables to establish a risk stratification model to predict recurrence and survival rates. MATERIALS AND METHODS: We studied 230 patients with renal cell carcinoma (stages T(1-4) N(x) M(0)) who underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 48 months (range 3 to 140). Univariate and multivariate analyses were performed, and the influence of clinical presentation, histological tumor size, tumor grade, lymph node involvement and microvascular tumor invasion on disease-free and cancer specific survival curves was determined. A composition model based on independent prognostic variables was then created to stratify tumors into low, intermediate and high risk of progression. RESULTS: The tumor recurrence rate was 17% (39 of 230) and the cancer specific mortality rate was 13% (31 of 230). Multivariate analyses determined that microvascular tumor invasion, tumor grade and tumor size were the only independent prognostic factors. Disease-free survival rates for low, intermediate and high risk tumors were 94.7%, 56.8% and 13.1%, respectively. Cancer specific survival rates were 94.7%, 61.7% and 32.0%, respectively. CONCLUSIONS: Tumor size, Fuhrman grade and microvascular tumor invasion are strong and independent predictors of survival of patients with renal cell carcinoma. Risk assessment and stratification based on this triad of pathological features may allow better individualization of followup schedules and trials of adjuvant treatment for patients with renal cell carcinoma.

CpG hypermethylation of promoter region and inactivation of E-cadherin gene in human bladder cancer.

Several studies have shown that E-cadherin expression is lost during malignant transformation. We hypothesized that CpG methylation in the promoter region may inactivate the expression of the E-cadherin gene in human bladder cancer. Normal and bladder cancer samples from 51 patients were compared in terms of E-cadherin gene expression and methylation status by immunohistochemistry, methylation-specific polymerase chain reaction (MSP), and bisulfite genome-sequencing techniques. Ten different CpG sites (nt 863, 865, 873, 879, 887, 892, 901, 918, 920, and 940) in the promoter region were studied. Thirty-five of 51 (69%) bladder cancer samples lacked E-cadherin expression, whereas only six of 51 (12%) normal bladder samples lacked E-cadherin immunoreactivity. MSP analysis of bladder cancer samples suggested that 43 of 51 (84%) showed methylation of the promoter region, whereas only 12 of 51 (24%) normal bladder samples showed hypermethylation. Sodium bisulfite genome-sequencing analysis revealed that of 10 CpG sites, two sites (nt 892 and nt 940) showed 100% methylation in all the cancer samples analyzed. Other CpG sites were partially methylated (47-91%). Normal tissue showed only 12% methylation (range, 1-33%) on various CpG sites. Also supporting these data, E-cadherin-negative bladder cancer cell lines restored expression of the E-cadherin gene after treatment with the demethylating agent 5-aza-2'-deoxycytidine. The present study showed that CpG hypermethylation was an important mechanism of E-cadherin gene inactivation in bladder cancer and also that specific CpG sites consistently presented higher methylation levels than others. These findings may provide a better strategy for the diagnosis and management of bladder cancer.