mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants

Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan (R)-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20(+)/KRT5(-), 5-year DSS 0%, p < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20(+)/KRT- tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested)

Downregulation of Checkpoint Protein Kinase 2 in the Urothelium of Healthy Male Tobacco Smokers

With this letter to the editor we present for the first time a study on CHEK2 expression in normal urothelium of healthy male smokers, former smokers and non-smokers. We could show a statistically significant downregulation of this DNA repair gene in current smokers compared to non-smokers, suggesting that smoking downregulates CHEK2 in normal urothelium, probably associated with an early step in carcinogenesis of urothelial bladder carcinoma. (C) 2016 S. Karger AG, Base

Tumor budding correlates with tumor invasiveness and predicts worse survival in pT1 non-muscle-invasive bladder cancer

Tumor budding is defined as a single cell or a cluster of up to 5 tumor cells at the invasion front. Due to the difficulty of identifying patients at high risk for pT1 non-muscle-invasive bladder cancer (NMIBC) and the difficulties in T1 substaging, tumor budding was evaluated as a potential alternative and prognostic parameter in these patients. Tumor budding as well as growth pattern, invasion pattern and lamina propria infiltration were retrospectively evaluated in transurethral resection of the bladder (TURB) specimens from 92 patients with stage pT1 NMIBC. The presence of tumor budding correlated with multifocal tumors (p = 0.003), discontinuous invasion pattern (p = 0.039), discohesive growth pattern (p < 0.001) and extensive lamina propria invasion (p < 0.001). In Kaplan–Meier analysis, tumor budding was associated with significantly worse RFS (p = 0.005), PFS (p = 0.017) and CSS (p = 0.002). In patients who received BCG instillation therapy (n = 65), the absence of tumor budding was associated with improved RFS (p = 0.012), PFS (p = 0.011) and CSS (p = 0.022), with none of the patients suffering from progression or dying from the disease. Tumor budding is associated with a more aggressive and invasive stage of pT1 NMIBC and a worse outcome. This easy-to-assess parameter could help stratify patients into BCG therapy or early cystectomy treatment groups

Risk factors for bladder neck contracture after transurethral resection of the prostate

Introduction Transurethral resection of the prostate (TURP) is the most frequently used treatment of benign prostate hyperplasia with a prostate volume of <80 mL. A long-term complication is bladder neck contracture (BNC). The aim of the present study was to identify the risk factors for BNC formation after TURP. Methods We conducted a retrospective analysis of all TURP primary procedures which were performed at one academic institution between 2013 and 2018. All patients were analyzed and compared with regard to postoperative formation of a BNC requiring further therapy. Uni- and multivariable logistic regression analyses (MVAs) were performed to identify possible risk factors for BNC development. Results We included 1368 patients in this analysis. Out of these, 88 patients (6.4%) developed BNC requiring further surgical therapy. The following factors showed a statistically significant association with BNC development: smaller preoperative prostate volume (p = 0.001), lower resected prostate weight (p = 0.004), lower preoperative levels of prostate-specific antigen (PSA, p < 0.001), shorter duration of the surgery (p = 0.027), secondary transurethral intervention (due to urinary retention or gross hematuria) during inpatient stay (p = 0.018), positive (≥100  CFU/mL) preoperative urine culture (p = 0.010), and urethral stricture (US) formation requiring direct visual internal urethrotomy (DVIU) postoperatively after TURP (p < 0.001), in particular membranous (p = 0.046) and bulbar (p < 0.001) strictures. Preoperative antibiotic treatment showed a protective effect (p = 0.042). Histopathological findings of prostate cancer (PCA) in the resected prostate tissue were more frequent among patients who did not develop BNC (p = 0.049). On MVA, smaller preoperative prostate volume (p = 0.046), positive preoperative urine culture (p = 0.021), and US requiring DVIU after TURP (p < 0.001) were identified as independent predictors for BNC development. Conclusion BNC is a relevant long-term complication after TURP. In particular, patients with a smaller prostate should be thoroughly informed about this complication

Outcome of Patients with Pathological Tumor Stage T3 Urothelial Carcinoma of the Bladder following Radical Cystectomy in a Single-Center Series with 116 Patients

Objective: Outcome prediction of pT3 urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) remains challenging. The objective of our study was to determine high-risk patients with poor survival outcome in a heterogeneous group substaged pT3 who might profit from early adjuvant chemotherapy. Materials and Methods: We compiled clinicopathological and immunohistochemical data of E-cadherin (E-cad) expression in 116 patients with pT3 UCB after RC in our single-center series. Multivariable Cox regression models including substaged pT3 established clinicopathological features, and the expression of the predictive immunohistochemical feature E-cad was used to identify independent predictors on progression-free (PFS), cancer-specific (CSS) and overall survival (OS), respectively. Results: No significant differences were found addressing clinicopathological data and substaged pT3. In multivariable Cox regression models, lymph node involvement was an independent predictor for PFS (p < 0.001), CSS (p < 0.001) and OS (p = 0.002), respectively. Lymphovascular invasion (LVI) significantly influenced PFS (p = 0.016). ASA score 3/4 independently predicted CSS (p = 0.049) and OS (p = 0.032). Neither pT3 substages nor E-cad expression were significant prognosticators for survival. Conclusions: In pT3 UCB patients with ASA 3/4, positive lymph node status and/or presence of LVI, administration of chemotherapy should be considered due to the high risk of poor oncological outcome. The immunohistochemical marker E-cad was not an independent predictor

Short-Term and Long-Term Morbidity after Radical Cystectomy in Patients with NMIBC and Comparison with MIBC: Identifying Risk Factors for Severe Short-Term Complications

Introduction: RC represents a viable treatment option for certain NMIBC patients. However, studies investigating morbidity in the context of RC for NMIBC are scarce. The goal of the current study was to assess and compare morbidity after RC performed in patients with NMIBC and patients with MIBC and to identify risk factors for severe short-term complications. Methods: Medical records of 521 patients who underwent RC for bladder cancer were retrospectively reviewed. Patients were divided into patients with NMIBC and patients with MIBC. The groups were compared and risk factors for severe complications were identified. Results: RC for NMIBC was performed in 123 patients (23.6%). Histological upstaging was seen in 47 NMIBC patients (38.2%) and in 231 MIBC patients (58%, p < 0.001). OS was 29.8% and CSS was 15.5%. Both endpoints were higher for RC for MIBC (p < 0.001). More complications affecting the urinary diversion were seen with RC for NMIBC (p = 0.033) and more continent urinary diversions (p = 0.040) were performed in those patients. Obesity (p = 0.008), a higher ASA score (p = 0.004), and preoperative medical drug anticoagulation (p = 0.025) were risk factors for severe short-term morbidity after both, RC for NMIBC and for MIBC. Conclusion: Patients who underwent RC for NMIBC are exposed to a comparably high perioperative risk than patients with MIBC. RC seems to be a viable treatment option for certain NMIBC patients with a significant histological upstaging in both groups. In patients with obesity, a high ASA score, and with medical drug anticoagulation, the indication for surgery should be confirmed especially strict and possible treatment alternatives should be considered particularly thorough

Das Charisma des Herrschers

In den Herrschaftssystemen der Vormoderne beruhte Macht zu einem erheblichen Teil auf Vorstellungen von einer besonderen Ausstrahlung der Herrschenden. Für den politischen Erfolg war es entscheidend, dass diese Besonderheit überzeugend und nachhaltig vermittelt wurde und dass sie auf der anderen Seite die Zustimmung der Beherrschten fand. Die Beiträge des Bandes untersuchen, von der griechisch-römischen Antike ausgehend, in welchen Formen Vorstellungen vom Charisma des Herrschers ihren Ausdruck fanden. Es geht um die numinose Aura, mit der die privilegierte Nähe vormoderner Herrscher zu göttlichen Wesen bezeichnet wurde. Dabei wird zum einen für die Zeit des Hellenismus und der römischen Kaiserzeit ein breites Spektrum aufgezeigt. Einen zweiten Teil nehmen entsprechende Phänomene aus anderen Epochen und Kulturen ein

Body Composition as a Comorbidity-Independent Predictor of Survival following Nephroureterectomy for Urothelial Cancer of the Upper Urinary Tract

Radical nephroureterectomy (NUE) is the gold standard treatment for high-risk urothelial cancer of the upper urinary tract (UTUC). Besides sarcopenia and frailty, fat distribution is moving increasingly into focus. Components of body composition were assessed in patients undergoing NUE due to UTUC. The study cohort included 142 patients. By using CT-based measurements, the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured at the height of the third lumbar vertebra. Overall survival (OS) and cancer-specific survival (CSS) were estimated using univariable und multivariable Cox regression models. The prevalence of sarcopenia in the study population (n = 142) was 37%. OS and CSS were significantly reduced in sarcopenic patients. In the multivariable cox regression analysis, including age, ACE-27, T-stage, R-stage, LVI and necrosis, sarcopenia remained a significant risk factor of OS (HR, 1.77; 95% CI 1.02–3.07; p = 0.042) and CSS (HR, 2.17; 95% CI 1.18–3.99; p = 0.012). High visceral adipose tissue seems to be protective, although not statistically significant. Sarcopenia is a comorbidity-independent risk factor in patients who underwent NUE due to UTUC. Visceral fat represents a potentially protective factor. These results suggest that specific factors of body composition can be used for better risk stratification

Body Composition of Patients Undergoing Radical Cystectomy for Bladder Cancer: Sarcopenia, Low Psoas Muscle Index, and Myosteatosis Are Independent Risk Factors for Mortality

Abstract: Background: We assessed a wide array of body composition parameters to identify those most relevant as prognostic tools for patients undergoing radical cystectomy (RC) due to bladder cancer (BC). Methods: In this retrospective, single-center study, preoperative computed tomography (CT) scans of 657 patients were measured at the level of the 3rd lumbar vertebra (L3) to determine common body composition indices including sarcopenia, myosteatosis, psoas muscle index (PMI), subcutaneous and visceral fat index (SFI and VFI), visceral-to-subcutaneous fat ratio (VSR), and visceral obesity. Predictors of overall survival (OS) and cancer-specific survival (CSS) were identified in univariate and multivariate survival analysis. Results: Sarcopenia and a low PMI were independently associated with shorter OS (Sarcopenia: HR 1.30; 95% CI 1.02–1.66; p = 0.04 and a low PMI: HR 1.32; 95% CI 1.02–1.70; p = 0.03) and CSS (Sarcopenia: HR 1.64; 95% CI 1.19–2.25; p < 0.01 and a low PMI: HR 1.41; 95% CI 1.02–1.96; p = 0.04). Myosteatosis, measured as decreasing average Hounsfield units of skeletal muscle, was an independent risk factor for OS (HR 0.98; 95% CI 0.97–1.00; p = 0.01) and CSS (HR 0.98; 95% CI 0.96–1.00; p < 0.05). The assessed adipose tissue indices were not significant predictors for OS and CSS. Conclusions: Sarcopenia, a low PMI, and myosteatosis are independent predictors for OS and CSS in patients undergoing radical cystectomy for bladder cancer