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Urothelial cancer (UC) is one of the most common cancers in Europe and is also one of the costliest to treat. When first line therapies show initial success, around 50% of cancers relapse and proceed to metastasis. In this study we assessed the Protein inhibitor of activated signal transducers and activators of transcription (PIAS)1 as a potential therapeutic target in urothelial cancer. PIAS1 is a key regulator of STAT1 signalling and may be implicated in carcinogenesis. In contrast to other cancer types PIAS1 protein expression is not significantly different in malignant areas of UC specimens compared to non-malignant tissue. In addition, we found that down-regulation and overexpression of PIAS1 had no effect on the viability or colony forming ability of tested cell lines. Whilst other studies of PIAS1 suggest an important biological role in cancer, this study shows that PIAS1 has no influence on reducing the cytotoxic effects of Cisplatin or cell recovery after DNA damage induced by irradiation. Taken together, these in vitro data demonstrate that PIAS1 is not a promising therapeutic target in UC cancer as previously shown in different entities such as prostate cancer (PCa). [ABSTRACT FROM AUTHOR]

Abstract: Background: The Bladder Cancer Research Consortium (BCRC) created nomograms to predict all-cause mortality (ACM), cancer-specific mortality (CSM), and recurrence after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). Objective: To perform a formal validation of the BCRC nomograms in a large multi-institutional patient cohort from Europe. Design, setting, and participants: Records of 2501 patients who underwent RC for UCB at eight European centers were reviewed. Complete information for external validation was available in 2404 patients for the ACM and CSM nomograms and in 2243 patients for the recurrence nomogram. Measurements: For the purpose of external validation, model discrimination was measured using the receiver operating characteristics derived area under the curve. Calibration plots examined the relationship between predicted and observed probabilities at 2 yr, 5 yr, and 8 yr. Decision curve analyses were applied to assess the net benefit derived from the three models. Results and limitations: The discrimination accuracies of the BCRC nomograms for ACM and CSM at 2 yr, 5 yr, and 8 yr after RC were 71.0%, 69.1%, and 68.2%, and 74.9%, 73.1%, and 72.4%, respectively. The accuracy of discrimination for the recurrence nomogram at the same time points was 76.5%, 75.3%, and 74.9%, respectively. Calibration plots revealed slight underestimations from ideal predictions. Decision curve analyses showed an increased net benefit for the use of the BCRC nomograms in this cohort. Limitations include the retrospective study design, potential surgeon bias, and lack of a central pathologic review. Conclusions: The ACM, CSM, and recurrence nomograms showed acceptable predictive accuracies and could thus be adopted into clinical practice in UCB patients treated in Europe. [Copyright &y& Elsevier]

Background/Aims/Objectives: To evaluate the influence of body mass index (BMI) on complications and oncological outcomes in patients undergoing radical cystectomy (RC)., Methods: Clinical and histopathological parameters of patients have been prospectively collected within the "PROspective MulticEnTer RadIcal Cystectomy Series 2011". BMI was categorized as normal weight (<25 kg/m2), overweight (≥25-29.9 kg/m2) and obesity (≥30 kg/m2). The association between BMI and clinical and histopathological endpoints was examined. Ordinal logistic regression models were applied to assess the influence of BMI on complication rate and survival., Results: Data of 671 patients were eligible for final analysis. Of these patients, 26% (n = 175) showed obesity. No significant association of obesity on tumour stage, grade, lymph node metastasis, blood loss, type of urinary diversion and 90-day mortality rate was found. According to the -American Society of Anesthesiologists score, local lymph node (NT) stage and operative case load patients with higher BMI had significantly higher probabilities of severe complications 30 days after RC (p = 0.037). The overall survival rate of obese patients was superior to normal weight patients (p = 0.019)., Conclusions: There is no evidence of correlation between obesity and worse oncological outcomes after RC. While obesity should not be a parameter to exclude patients from cystectomy, surgical settings need to be aware of higher short-term complication risks and obese patients should be counselled -accordingly., (© 2018 S. Karger AG, Basel.)

Objective: To externally validate the pT4a-specific risk model for cancer-specific survival (CSS) proposed by May et al. (Urol Oncol 2013; 31: 1141-1147) and to develop a new pT4a-specific nomogram predicting CSS in an international multicentre cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) PATIENTS AND METHODS: Data from 856 patients with pT4a UCB treated with RC at 21 centres in Europe and North-America were assessed. The risk model proposed by May et al., which includes female gender, presence of positive lymphovascular invasion (LVI) and lack of adjuvant chemotherapy administration as adverse predictors for CSS, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver-operating characteristic-derived area under the curve. A nomogram for predicting CSS in pT4a UCB after RC was developed after internal validation based on multivariable Cox proportional hazards regression analysis evaluating the impact of clinicopathological variables on CSS. Decision-curve analyses were applied to determine the net benefit derived from the two models., Results: The estimated 5-year-CSS after RC was 34% in our cohort. The risk model devised by May et al. predicted individual 5-year-CSS with an accuracy of 60.1%. In multivariable Cox proportional hazards regression analysis, female gender (hazard ratio [HR] 1.45), LVI (HR 1.37), lymph node metastases (HR 2.54), positive soft tissue surgical margins (HR 1.39), neoadjuvant (HR 2.24) and lack of adjuvant chemotherapy (HR 1.67, all P < 0.05) were independent predictors of an adverse CSS rate and formed the features of our nomogram with a predictive accuracy of 67.1%. Decision-curve analyses showed higher net benefits for the use of the newly developed nomogram in our cohort over all thresholds., Conclusions: The risk model devised by May et al. was validated with moderate discrimination and was outperformed by our newly developed pT4a-specific nomogram in the present study population. Our nomogram might be particularly suitable for postoperative patient counselling in the heterogeneous cohort of patients with pT4a UCB., (© 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.)

Introduction: Asian scientists have now increasingly begun to contribute to globalization; yet it is not clear whether publishing in the field of urology is paralleled by elevated cross-continental scientific publishing., Materials and Methods: An exemplary bibliometric analysis of urologic journals from 3 different continents was conducted between 2002 and 2012. Based on the ISI Web of Knowledge Journal Citation Reports, 2 urologic journals with similar impact factors (IFs) in 2013 were selected from Europe ('British Journal of Urology International', 'World Journal of Urology'), Asia ('International Journal of Urology', 'Asian Journal of Andrology') and North America ('Urologic Oncology-Seminars and Original Investigations', 'Urology'). The home continent of the journal, the workplace continental affiliation of the last author, article type (clinical, experimental or review) as well as the IF were documented., Results: Most authors published their manuscripts in journals from the same continent in which they worked. However, a significant increase in cross-continental publishing was apparent from 2002 to 2012. Asians publishing in North America increased from 17% in 2002 to 35% in 2012. Europeans also increased the number of articles they published in North American journals, while publications from North American authors were shifted towards both European and Asian journals. Experimental and clinical articles showed significant increases in cross-continental publishing, while review publishing showed no significant change. The average IF for authors from all 3 continents increased from 2002 to 2012 (p < 0.001). The largest increase in the IF was found for Asian authors (0.11 per year)., Conclusions: Cross-continental publication significantly increased during the period from 2002 to 2012. The impact that the Asian authors have experienced was found to be gradually impacting the North American and European colleagues., (© 2015 S. Karger AG, Basel.)

Purpose: To perform the first external validation of a recently identified association between disease-free survival at two years (DFS2) or three years (DFS3) and overall survival at five years (OS5) in patients after radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB)., Methods and Methods: Records of 2483 patients who underwent RC for UCB at eight European centers between 1989 and 2008 were reviewed. The cohort included 1738 patients with pT2-4a tumors and negative soft tissue surgical margins (STSM) according to the selection criteria of the previous study (study group (SG)). In addition, 745 patients with positive STSM or other tumor stages (pT0-T1, pT4b) that were excluded from the previous study (excluded patient group (EPG)) were evaluated. Kappa statistic was used to measure the agreement between DFS2 or DFS3 and OS5., Results: The overall agreement between DFS2 and OS5 was 86.5% (EPG: 88.7%) and 90.1% (EPG: 92.1%) between DFS3 and OS5. The kappa values for comparison of DFS2 or DFS3 with OS5 were 0.73 (SE: 0.016) and 0.80 (SE: 0.014) respectively for the SG, and 0.67 (SE: 0.033) and 0.78 (SE: 0.027) for the EPG (all p-values <0.001)., Conclusions: We externally validated a correlation between DFS2 or DFS3 and OS5 for patients with pT2-4a UCB with negative STSM that underwent RC. Furthermore, this correlation was found in patients with other tumor stages regardless of STSM status. These findings indicate DFS2 and DFS3 as valid surrogate markers for survival outcome with RC., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The prognostic significance of venous involvement and tumour thrombus level in renal cell carcinoma (RCC) remains highly controversial. In 2010, the American Joint Committee on Cancer (AJCC) and the Union International Centre le Cancer (UICC) revised the RCC staging system (7th edition) based on tumour thrombus level, differentiating the T stage of tumours limited to renal-vein-only involvement., Objective: We aimed to evaluate the impact of tumour thrombus extension in a multi-institutional cohort of patients., Design, Setting, and Participants: An international consortium of 11 institutions was established to retrospectively review a combined cohort of 1215 patients undergoing radical nephrectomy and tumour thrombectomy for RCC, including 585 patients with inferior vena cava (IVC) involvement or higher., Measurements: Predictive factors of survival, including histology, tumour thrombus level, nodal status, Fuhrman grade, and tumour size, were analysed., Results and Limitations: A total of 1122 patients with complete data were reviewed. The median follow-up for all patients was 24.7 mo, with a median survival of 33.8 mo. The 5-yr survival was 43.2% (renal vein involvement), 37% (IVC below the diaphragm), and 22% with caval involvement above the diaphragm. On multivariate analysis, tumour size (hazard ratio [HR]: 1.64 [range: 1.03-2.59]; p=0.036), Fuhrman grade (HR: 2.26 [range: 1.65-3.1]; p=0.000), nodal metastasis (HR: 1.32 [range: 1.09-1.67]; p=0.005), and tumour thrombus level (HR: 2.10 [range: 1.53-3.0]; p=0.00) correlated independently with survival., Conclusions: Based on analysis of the largest known cohort of patients with RCC along with IVC and atrial thrombus involvement, tumour thrombus level is an independent predictor of survival. Our findings support the changes to the latest AJCC/UICC staging system., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)