S.C. Müller

Characterization and risk stratification of prostate cancer in patients undergoing radical cystoprostatectomy

To describe the prevalence of incidental prostate cancer in patients undergoing radical cystoprostatectomy for bladder malignancy; to quantify the association between incidental prostate cancer and mortality in these patients; and to quantify the association between incidental prostate cancer and age in radical cystoprostatectomy specimens.

Einfluss des Alters auf das karzinomspezifische Überleben nach radikaler Zystektomie

BACKGROUND The therapeutic gold standard of muscle-invasive tumour stages is radical cystectomy (RC), but there are still conflicting reports about associated morbidity and mortality and the oncologic benefit of RC in elderly patients. The aim of the present study was the comparison of overall (OS) and cancer-specific survival (CSS) in patients <75 and >75 years of age (median follow-up was 42 months). PATIENTS AND METHODS Clinical and histopathological data of 2,483 patients with urothelial carcinoma and consecutive RC were collated. The study group was dichotomized by the age of 75 years at RC. Statistical analyses comprising an assessment of postoperative mortality within 90 days, OS and CSS were assessed. Multivariate logistic regression and survival analyses were performed. RESULTS The 402 patients (16.2%) with an age of ≥75 years at RC showed a significantly higher local tumour stage (pT3/4 and/or pN+) (58 vs 51%; p=0.01), higher tumour grade (73 vs 65%; p=0.003) and higher rates of upstaging in the RC specimen (55 vs 48%; p=0.032). Elderly patients received significantly less often adjuvant chemotherapy (8 vs 15%; p<0.001). The 90-day mortality was significantly higher in patients ≥75 years (6.2 vs 3.7%; p=0.026). When adjusted for different variables (gender, tumour stage, adjuvant chemotherapy, time period of RC), only in male patients and locally advanced tumour stages was an association with 90-day mortality noticed. The multivariate analysis showed that patients ≥75 years of age have a significantly worse OS (HR=1.42; p<0.001) and CSS (HR=1.27; p=0.018). CONCLUSIONS An age of ≥75 years at RC is associated with a worse outcome. Prospective analyses including an assessment of the role of comorbidity and possibly age-dependent tumour biology are warranted.

Chemolitholysis and Lithotripsy of Infectious Urinary Stones – An in vitro Study

Objectives: This study was performed to look for an improvement of therapeutic strategies with regard to the treatment of infectious urinary stones using artificial stones made of struvite and apatite (‘Bon(n) stones’) which are comparable to their natural counterparts. Materials and Methods: Using an experimental arrangement simulating the physiological conditions in the upper urinary tract, the efficacy of artificial urine (pH 5.7), Suby G solution (pH 3.6), mixtures of artificial urine with Suby G (pH 3.9 and pH 4.1) in dissolving artificial struvite and apatite stones (Bon(n) stones) was investigated. The dissolution of natural infectious urinary stones was also measured. Additionally, investigations on shock-wave lithotripsy (SWL) combined with initial chemolytic treatment of the stones were performed. Results: The efficacy of Suby G solution in dissolving artificial stones was demonstrated. Direct comparison of chemolysis of natural and artificial stones showed no statistical difference between infectious urinary stones and Bon(n) stones of the same material. The investigations on SWL showed a significant improvement on stone comminution, especially of artificial apatite stones after initial chemolytic treatment with Suby G. Conclusion: New basics to improve dissolution of infectious urinary stones have been developed by performing standardized in vitro investigations. Local chemolysis with Suby G is an effective tool in the treatment of infectious stone disease. SWL can be improved by varying the physical properties of infectious stones through initial treatment with Suby G solution.

Prediction of outcome in patients with urothelial carcinoma of the bladder following radical cystectomy using artificial neural networks.

AIM The outcome of patients with urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) shows remarkable variability. We evaluated the ability of artificial neural networks (ANN) to perform risk stratification in UCB patients based on common parameters available at the time of RC. METHODS Data from 2111 UCB patients that underwent RC in eight centers were analysed; the median follow-up was 30 months (IQR: 12-60). Age, gender, tumour stage and grade (TURB/RC), carcinoma in situ (TURB/RC), lymph node status, and lymphovascular invasion were used as input data for the ANN. Endpoints were tumour recurrence, cancer-specific mortality (CSM) and all-cause death (ACD). Additionally, the predictive accuracies (PA) of the ANNs were compared with the PA of Cox proportional hazards regression models. RESULTS The recurrence-, CSM-, and ACD- rates after 5 years were 36%, 33%, and 46%, respectively. The best ANN had 74%, 76% and 69% accuracy for tumour recurrence, CSM and ACD, respectively. Lymph node status was one of the most important factors for the networks decision. The PA of the ANNs for recurrence, CSM and ACD were improved by 1.6% (p = 0.247), 4.7% (p < 0.001) and 3.5% (p = 0.007), respectively, in comparison to the Cox models. CONCLUSIONS ANN predicted tumour recurrence, CSM, and ACD in UCB patients after RC with reasonable accuracy. In this study, ANN significantly outperformed the Cox models regarding prediction of CSM and ACD using the same patients and variables. ANNs are a promising approach for individual risk stratification and may optimize individual treatment planning.

External validation of disease-free survival at 2 or 3 years as a surrogate and new primary endpoint for patients undergoing radical cystectomy for urothelial carcinoma of the bladder

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.

Prediction of Locally Advanced Urothelial Carcinoma of the Bladder Using Clinical Parameters before Radical Cystectomy - A Prospective Multicenter Study

Introduction: We aimed at developing and validating a pre-cystectomy nomogram for the prediction of locally advanced urothelial carcinoma of the bladder (UCB) using clinicopathological parameters. Materials and Methods: Multicenter data from 337 patients who underwent radical cystectomy (RC) for UCB were prospectively collected and eligible for final analysis. Univariate and multivariate logistic regression models were applied to identify significant predictors of locally advanced tumor stage (pT3/4 and/or pN+) at RC. Internal validation was performed by bootstrapping. The decision curve analysis (DCA) was done to evaluate the clinical value. Results: The distribution of tumor stages pT3/4, pN+ and pT3/4 and/or pN+ at RC was 44.2, 27.6 and 50.4%, respectively. Age (odds ratio (OR) 0.980; p < 0.001), advanced clinical tumor stage (cT3 vs. cTa, cTis, cT1; OR 3.367; p < 0.001), presence of hydronephrosis (OR 1.844; p = 0.043) and advanced tumor stage T3 and/or N+ at CT imaging (OR 4.378; p < 0.001) were independent predictors for pT3/4 and/or pN+ tumor stage. The predictive accuracy of our nomogram for pT3/4 and/or pN+ at RC was 77.5%. DCA for predicting pT3/4 and/or pN+ at RC showed a clinical net benefit across all probability thresholds. Conclusion: We developed a nomogram for the prediction of locally advanced tumor stage pT3/4 and/or pN+ before RC using established clinicopathological parameters.

Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer.

Introduction: Yes-associated protein 1 (YAP1), the nuclear effector of the Hippo pathway, plays an important role in many tumor entities. We evaluated staining and clinical significance of YAP1 and phosphorylated YAP1 (pYAP1) in urothelial bladder cancer (BCA). Materials and Methods: We used a tissue micorarray with samples of patients with muscle-invasive bladder cancer (MIBC, n = 192), non-muscle-invasive bladder cancer (NMIBC, n = 192) and normal urothelial bladder tissue (CTRL, n = 38) to determine the immunhistochemical staining of YAP1 and pYAP1. Cytoplasmatic and nuclear levels were evaluated. The t test was used for comparative analysis. Overall survival and progression-free survival were evaluated by Kaplan-Meier estimates and the Cox proportional hazard regression model. Results: Nuclear YAP1 as well as cytoplasmatic pYAP1 levels were higher in CTRL than in BCA, whereby both - NMIBC and MIBC - had lower levels than CTRL. Among patients with MIBC, cytoplasmatic YAP1 and pYAP1 staining decreased with advanced stage. YAP1 and pYAP1 staining did not correlate with the recurrence rate, progression-free, cancer-specific or overall survival. Conclusions: Immunhistochemical staining and subcellular localization of YAP1 and pYAP1 are different for BCA, NMIBC, MIBC and CTRL, indicating that the Hippo pathway is involved in urothelial carcinogenesis.

Management of extended penile trauma with bilateral rupture of cavernosal bodies and complete urethral disruption.

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Influence of Body Mass Index on Clinical Outcome Parameters, Complication Rate and Survival after Radical Cystectomy: Evidence from a Prospective European Multicentre Study

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.

Primary Urethral Plasmacytoma Treated with High-Dose-Rate Brachytherapy: A Case Report

Primary urethral solitary plasmacytoma is a very rare variant of extramedullary plasmacytoma. In total, only 9 cases have been reported so far. Patients were treated either by surgery or by external radiation therapy. Here, we report on a 22-year-old man, initially presenting with a palpable induration at the penis, intermittent dysuria and haematospermia, which was due to histologically confirmed solitary urethral kappa-restricted plasmacytoma. The patient subsequently underwent percutaneous and endo-urethral high-dose-rate brachytherapy with a total dose of 42 Gy applied in 14 fractions. Besides an uncomplicated urinary tract infection and hyperpigmentation of the penis, the patient tolerated the radiotherapy well and is still free of disease after 15 months follow-up.