Mitofusin-2 Down-Regulation Predicts Progression of Non-Muscle Invasive Bladder Cancer

Identification of markers predicting disease outcome is a major clinical issue for non-muscle invasive bladder cancer (NMIBC). The present study aimed to determine the role of the mitochondrial proteins Mitofusin-2 (Mfn2) and caseinolytic protease P (ClpP) in predicting the outcome of NMIBC. The study population consisted of patients scheduled for transurethral resection of bladder tumor upon the clinical diagnosis of bladder cancer (BC). Samples of the main bladder tumor and healthy-looking bladder wall from patients classified as NMIBC were tested for Mfn2 and ClpP. The expression levels of these proteins were correlated to disease recurrence, progression. Mfn2 and ClpP expression levels were significantly higher in lesional than in non-lesional tissue. Low-risk NMIBC had significantly higher Mfn2 expression levels and significantly lower ClpP expression levels than high-risk NMIBC; there were no differences in non-lesional levels of the two proteins. Lesional Mfn2 expression levels were significantly lower in patients who progressed whereas ClpP levels had no impact on any survival outcome. Multivariable analysis adjusting for the EORTC scores showed that Mfn2 downregulation was significantly associated with disease progression. In conclusion, Mfn2 and ClpP proteins were found to be overexpressed in BC as compared to non-lesional bladder tissue and Mfn2 expression predicted disease progression

The Percutaneous Nephrolithotomy Global Study: Classification of Complications

Purpose: This study evaluated postoperative complications of percutaneous nephrolithotomy (PCNL) and the influence of selected factors on the risk of complications using the Clinical Research Office of the Endourological Society (CROES) PCNL Global Study database. Patients and Methods: The CROES PCNL Global Study collected prospective data for consecutive patients who were treated with PCNL at centers around the world for 1 year. Complications were evaluated by the modified Clavien classification system. Results: Of 5724 patients with Clavien scores, 1175 (20.5%) patients experienced one or more complications. The most frequent complications were fever and bleeding. Urinary leakage, hydrothorax, hematuria, urinary tract infection, pelvic perforation, and urinary fistula also occurred in >= 20 patients in each group. The majority of complications (n = 634, 54.0%) were classified as Clavien grade I. Two patients died in the postoperative period. The largest absolute increases in mean Clavien score were associated with American Society of Anesthesiologists (ASA) physical status classification IV (0.75) or III (0.34), anticoagulant medication use (0.29), positive microbiologic culture from urine (0.24), and the presence of concurrent cardiovascular disease (0.15). Multivariate regression analysis revealed that operative time and ASA score were significant predictors of higher mean Clavien scores. Conclusion: The majority of complications after PCNL are minor. Longer operative time and higher ASA scores are associated with the risk of more severe postoperative complications in PCNL

Evaluation of Patterns of Presentation, Practice, and Outcomes of Upper Tract Urothelial Cancer: Protocol for an Observational, International, Multicenter, Cohort Study by the Clinical Research Office of the Endourology Society

Background: Available guidelines on the management of upper tract urothelial carcinoma (UTUC) are restricted due to the lack of strong evidence-based recommendations. Adequate, well-powered randomized trials are missing due to the rarity of the disease. To overcome this problem, we need alternative study designs to provide generalizable data. Objective: The primary aim of this registry is to provide a real-world overview on patterns of presentation and management of UTUC. Secondary objectives include comparison of outcomes of different treatments and tumor stages and evaluation of compliance with the current European Association of Urology recommendations for UTUC. Methods: For this observational, international, multicenter, cohort study, clinical data of consecutive patients suspected of having UTUC, irrespective of type of management, will be prospectively collected up to 5 years after inclusion. Data on the patterns of presentation, diagnostics, and treatment as well as short-, mid-, and long-term oncological and functional outcomes will be analyzed. Possible associations between variables, basal characteristics, and outcomes will be tested by multivariable analyses. The methodology will address potential sources of bias and confounders. Results: The registry was initiated in November 2014 after obtaining institutional review board approval. Data collection started in December 2014. At the time of submission of this manuscript, 2451 patients from 125 centers from 37 countries were included. Inclusion of patients will be closed 5 years after initiation of the registry. Quality checks will be performed centrally with continuous communication and feedback with the centers to ensure accuracy. The first results are expected in the first trimester of 2020. Conclusions: This large observational prospective cohort will generate landmark "real-world" data and hypotheses for further studies. We expect these data to optimize the management of UTUC, provide insights on harms and benefits of treatment, and serve as quality control

Presence and severity of lower urinary tract symptoms are inversely correlated with the risk of prostate cancer on prostate biopsy

BACKGROUND: The assessment of lower urinary tract symptoms (LUTS) is common part of urological investigation. Furthermore, patients bother of prostate cancer (PCa) when they are affected of LUTS. This study was aimed to determine whether the presence and severity of LUTS, as assessed by the International Prostate Symptoms Score (IPSS), could help to identify patients at higher risk of prostate cancer (PCa) on prostate biopsy (PBx). In this effort, an initial PCa predictive model was calculated and IPSS was subsequently added. The diagnostic accuracy of both models was compared. METHODS: The analysis of prospectively collected data of patients scheduled for PBx at four academic hospitals between January 2012 and June 2015 was performed. Univariate and multivariate analysis assessed the correlation between the IPSS and the risk of being diagnosed with PCa; Receiver operator characteristic curve (ROC) analysis evaluated the predictive models including or not the IPSS. RESULTS: Of the 1366 enrolled patients, 706 (52%) were diagnosed with PCa. Patients with PCa had a significantly lower IPSS (10.6 +/- 7.4 vs. 12.7 +/- 8.1) than those with benign diagnosis. Multivariate logistic regression analysis showed that age, prostate-specific antigen (PSA), prostate volume and IPSS were the most significant predictors of PBx outcome, (OR 1.61, P=0.001; OR 1.20, P=0.001; OR 0.97, P=0.001; OR 0.74, P=0.004; respectively). ROC curve analysis showed that the addition of IPSS to the predictive model based on age, PSA, DRE and prostate volume significantly improved the model diagnostic accuracy (AUC: 0.776 vs. 0.652; P=0.001). CONCLUSIONS: Presence and severity of LUTS are inversely correlated with the risk of being diagnosed with PCa at PBx. Incorporating the IPSS into predictive models may reduce the risk of unnecessary PBxs.info:eu-repo/semantics/publishedVersio

Development and Internal Validation of Novel Nomograms Based on Benign Prostatic Obstruction-Related Parameters to Predict the Risk of Prostate Cancer at First Prostate Biopsy

The present study aimed to determine the ability of novel nomograms based onto readily-available clinical parameters, like those related to benign prostatic obstruction (BPO), in predicting the outcome of first prostate biopsy (PBx). To do so, we analyzed our Internal Review Board-approved prospectively-maintained PBx database. Patients with PSA>20 ng/ml were excluded because of their high risk of harboring prostate cancer (PCa). A total of 2577 were found to be eligible for study analyses. The ability of age, PSA, digital rectal examination (DRE), prostate volume (PVol), post-void residual urinary volume (PVR), and peak flow rate (PFR) in predicting PCa and clinically-significant PCa (CSPCa)was tested by univariable and multivariable logistic regression analysis. The predictive accuracy of the multivariate models was assessed using receiver operator characteristic curves analysis, calibration plot, and decision-curve analyses (DCA). Nomograms predicting PCa and CSPCa were built using the coefficients of the logit function. Multivariable logistic regression analysis showed that all variables but PFR significantly predicted PCA and CSPCa. The addition of the BPO-related variables PVol and PVR to a model based on age, PSA and DRE findings increased the model predictive accuracy from 0.664 to 0.768 for PCa and from 0.7365 to 0.8002 for CSPCa. Calibration plot demonstrated excellent models' concordance. DCA demonstrated that the model predicting PCa is of value between ~15 and ~80% threshold probabilities, whereas the one predicting CSPCa is of value between ~10 and ~60% threshold probabilities. In conclusion, our novel nomograms including PVR and PVol significantly increased the accuracy of the model based on age, PSA and DRE in predicting PCa and CSPCa at first PBx. Being based onto parameters commonly assessed in the initial evaluation of men “prostate health,” these novel nomograms could represent a valuable and easy-to-use tool for physicians to help patients to understand their risk of harboring PCa and CSPCa

Modulation of complement activation by pentraxin-3 in prostate cancer.

Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possible modulator of Complement activation in the development of this neoplasia. We performed a single center cohort study; from January 2017 through December 2018, serum and prostate tissue samples were obtained from 620 patients undergoing prostate biopsy. A group of patients with benign prostatic hyperplasia (BPH) underwent a second biopsy within 12-36 months demonstrating the presence of a prostate cancer (Group A, n = 40) or confirming the diagnosis of BPH (Group B, N = 40). We measured tissue PTX3 protein expression together with complement activation by confocal microscopy in the first and second biopsy in group A and B patients. We confirmed that that PTX3 tissue expression in the first biopsy was increased in group A compared to group B patients. C1q deposits were extensively present in group A patients co-localizing and significantly correlating with PTX3 deposits; on the contrary, C1q/PTX3 deposits were negative in group B. Moreover, we found a significantly increased expression of C3a and C5a receptors within resident cells in group A patient. Interestingly, C1q/PTX3 deposits were not associated with activation of the terminal Complement complex C5b-9; moreover, we found a significant increase of Complement inhibitor CD59 in cancer tissue. Our data indicate that PTX3 might play a significant pathogenic role in the development of this neoplasia through recruitment of the early components of Complement cascade with hampered activation of terminal Complement pathway associated with the upregulation of CD59. This alteration might lead to the PTX3-mediated promotion of cellular proliferation, angiogenesis and insensitivity to apoptosis possible leading to cancer cell invasion and migration

Patient's satisfaction after 2-piece inflatable penile prosthesis implantation: An Italian multicentric study.

Introduction: Penile prosthesis implant represents a valuable solution for pts with severe erectile dysfunction (ED), non-responders to medical management. The aim of our study was to evaluate the satisfaction of patients (pts) after 2-pieces inflatable penile prosthesis (IPP). Aim of the study: to evaluate safety, reliability and post-operative patient's satisfaction after implantation of two-pieces IPP. Materials and Methods: This retrospective multicentric analysis concerns a group of 42 patients undergone 2-pieces IPP implantation from November 2005 to November 2013, in four Centers of proven experience. As a first step, a detailed review of all clinical reports was performed. Secondly, every patient was asked to fill the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) specifically modified, in order to assess their own satisfaction after surgery and, its impact on patient's quality of sexual life. Results: 42 pts were evaluated (AMS-Ambicor: 28; Coloplast- Excell: 14); mean age, at time of operation: 60,7 years; mean follow up: 27,6 months; etiology of ED: vascular 23,8%, diabetes 19%, La Peyronie D. 7,1%, consequence of radical prostatectomy 31%, consequence of other pelvic surgery 11,9%, spinal trauma 7%. Mean operative time: 117 ± 58 min, mean postoperative hospital stay 3 ± 1,6 days. Post operative short-term complications: 4 pts (9,5%). Post operative long-term complications: 4 pts (9,5%). Long-term functional results (Questionnaire): 71% of pts (30) reported regular use of the prosthesis, at least 1 time/week, the satisfaction was good in 42% of pts (18), quite good in 33,3% (14), quite bad in 2,4% (1), very bad in 7,1% (3), 6 pts (14,4%) didn't answer. Conclusions: 2 pieces IPP appears to be associated with a low complication rate and good satisfaction of pts especially in the elderly. It also assures satisfactory rates of aesthetics and functional results