Stress Urinary Incontinence: An Unsolved Clinical Challenge

Stress urinary incontinence is still a frequent problem for women and men, which leads to pronounced impairment of the quality of life and withdrawal from the social environment. Modern diagnostics and therapy improved the situation for individuals affected. But there are still limits, including the correct diagnosis of incontinence and its pathophysiology, as well as the therapeutic algorithms. In most cases, patients are treated with a first-line regimen of drugs, possibly in combination with specific exercises and electrophysiological stimulation. When conservative options are exhausted, minimally invasive surgical therapies are indicated. However, standard surgeries, especially the application of implants, do not pursue any causal therapy. Non-absorbable meshes and ligaments have fallen into disrepute due to complications. In numerous countries, classic techniques such as colposuspension have been revived to avoid implants. Except for tapes in the treatment of stress urinary incontinence in women, the literature on randomized controlled studies is insufficient. This review provides an update on pharmacological and surgical treatment options for stress urinary incontinence; it highlights limitations and formulates wishes for the future from a clinical perspective

Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer

<p>Abstract</p> <p>Background</p> <p>Fibronectin 1 (<it>FN1</it>) is a glycoprotein involved in cellular adhesion and migration processes. The aim of this study was to elucidate the role of <it>FN1 </it>in development of renal cell cancer (RCC) and to determine a prognostic relevance for optimal clinical management.</p> <p>Methods</p> <p>212 renal tissue samples (109 RCC, 86 corresponding tissues from adjacent normal renal tissue and 17 oncocytomas) were collected from patients undergoing surgery for renal tumors and subjected to total RNA extraction. Detection of <it>FN1 </it>mRNA expression was performed using quantitative real time PCR, three endogenous controls, renal proximal tubular epithelial cells (RPTEC) as biological control and the ΔΔCt method for calculation of relative quantities.</p> <p>Results</p> <p>Mean tissue specific <it>FN1 </it>mRNA expression was found to be increased approximately seven fold comparing RCC and corresponding kidney control tissues (p < 0.001; ANOVA). Furthermore, tissue specific mean <it>FN1 </it>expression was increased approx. 11 fold in clear cell compared to papillary RCC (p = 9×10^-5; Wilcoxon rank sum test). Patients with advanced disease had higher <it>FN1 </it>expression when compared to organ-confined disease (p < 0.001; Wilcoxon rank sum test). Applying subgroup analysis we found a significantly higher <it>FN1 </it>mRNA expression between organ-confined and advanced disease in the papillary and not in the clear cell RCC group (p = 0.02 vs. p = 0.2; Wilcoxon rank sum test). There was an increased expression in RCC compared to oncocytoma (p = 0.016; ANOVA).</p> <p>Conclusions</p> <p>To our knowledge, this is the first study to show that <it>FN1 </it>mRNA expression is higher in RCC compared to normal renal tissue. <it>FN1 </it>mRNA expression might serve as a marker for RCC aggressiveness, indicating early systemic progression particularly for patients with papillary RCC.</p

Preoperative C-Reactive Protein in the Serum: A Prognostic Biomarker for Upper Urinary Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy

Objective: To investigate the impact of preoperative serum C-reactive protein (CRP) on clinicopathological features and prognosis in patients with upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU). Patients andMethods: Data of 265 patients from three German centers who underwent RNU for UTUC without neoadjuvant chemotherapy between 1990 and 2012 were evaluated. Mean follow-up was 37 months (interquartile range 9-48). CRP was analyzed as a categorical and continuous variable for the prediction of recurrence-free survival (RFS), disease-specific survival (DSS) and all-cause survival (ACS) using uni- and multivariate Cox regression analyses. Results: The optimal cutoff for CRP was calculated by the Youden index at 0.90 mg/dl. Elevated CRP was significantly associated with pT3/4 and pN+ in a preoperative model including age, gender, tumor multifocality, tumor localization and the Eastern Cooperative Oncology Group Performance Status. In a multivariable Cox regression model adjusted for features significant in univariable analysis, categorized and continuous CRP levels were both independent predictors for RFS [hazard ratio (HR) 1.18, p = 0.050; HR 1.03, p = 0.012] and DSS (HR 1.61, p = 0.026; HR 1.06, p = 0.001). Continuous CRP was an independent predictor for ACS (HR 1.05, p = 0.036). Conclusions: Elevated preoperative CRP is significantly associated with aggressive tumor biology and an independent predictor for poor survival after RNU. Preoperative serum CRP represents an easily obtainable and cost-effective marker in UTUC and may help in counseling patients with regard to operative management and/or adjuvant or neoadjuvant therapies

EAU-EANM Consensus Statements on the Role of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Patients with Prostate Cancer and with Respect to [177Lu]Lu-PSMA Radioligand Therapy

Funding support and role of sponsor: The EAU/EANM PSMA-based imaging and therapy consensus meeting was supported by an unrestricted educational grant from Novartis; Novartis had no influence over the content of the meeting or the publication. Medical writing support was funded by the European Association of Urology Research Foundation. Acknowledgements: The authors acknowledge Emily Spieker (Management Assistant, European Association of Urology) for project management. Medical writing support was provided by Angela Corstorphine of Kstorfin Medical Communications (KMC) limited.Peer reviewedPublisher PD

Prevention and early detection of prostate cancer

This Review was sponsored and funded by the International Society of Cancer Prevention (ISCaP), the European Association of Urology (EAU), the National Cancer Institute, USA (NCI) (grant number 1R13CA171707-01), Prostate Cancer UK, Cancer Research UK (CRUK) (grant number C569/A16477), and the Association for International Cancer Research (AICR

Enzalutamide in European and North American men participating in the AFFIRM trial

Objective To explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311).Patients and Methods Phase III, double-blind, placebo-controlled, multinational AFFIRM trial in men with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel. Participants were randomly assigned in a 2:1 ratio to receive oral enzalutamide 160 mg/day or placebo. The primary end point was overall survival (OS) in a post hoc analysis.Results Enzalutamide significantly improved OS compared with placebo in both EU and NA patients. The median OS in EU patients was longer than NA patients in both treatment groups. However, the relative treatment effect, expressed as hazard ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82) for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions. The tolerability profile of enzalutamide was comparable between EU and NA patients, with fatigue and nausea the most common adverse events. Four EU patients (4/461 enzalutamide-treated, 0.87%) and one NA patient (1/263 enzalutamide-treated, 0.38%) had seizures. The difference in median OS was related in part to the timing of development of mCRPC and baseline demographics on study entry.Conclusion This post hoc exploratory analysis of the AFFIRM trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA- and EU-treated patients, although the median OS was higher in EU relative to NA patients. Efficacy benefits were consistent across end points, with a comparable safety profile in both regions. © 2014 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International

Quantification of HLA class I molecules on renal cell carcinoma using Edman degradation

<p>Abstract</p> <p>Background</p> <p>Unimpaired HLA class I antigen presentation is a prerequisite for the recognition of tumor cells by cytotoxic T lymphocytes and thus essential for the success of anticancer immunotherapeutic concepts. Several approaches have been taken in the immunotherapy of metastatic renal cell carcinoma (RCC), however of limited success. HLA loss or down-regulation have often been reported and might interfere with immunotherapeutic approaches aimed at the recognition of HLA-presented peptides.</p> <p>Methods</p> <p>We employed a quantitative method of molecular analysis for the comparison of HLA amounts on primary tumor, normal kidney and metastases of RCC, using Edman degradation. We analyzed a series of 47 RCC samples including corresponding renal parenchyma, local lymph node metastases and distant metastases.</p> <p>Results</p> <p>Results of quantitative Edman degradation revealed significantly higher HLA yields on primary tumor and metastases compared to normal kidney tissue. This effect was shown not to result from infiltrating immune cells, since tumor-infiltrating lymphocytes had no influence on the overall HLA recovery from tumor tissue. Unexpectedly, we found a higher amount of HLA class I molecules on distant metastases compared to local lymph node metastases.</p> <p>Conclusion</p> <p>Edman degradation allows the direct quantitative comparison of HLA class I protein expression by tumor or normal tissue and metastases of RCC patients. Our results raise hopes for improving the success and effectiveness of future immunotherapeutic concepts for metastatic RCC.</p

Intensity modulated radiotherapy for high risk prostate cancer based on sentinel node SPECT imaging for target volume definition

BACKGROUND: The RTOG 94-13 trial has provided evidence that patients with high risk prostate cancer benefit from an additional radiotherapy to the pelvic nodes combined with concomitant hormonal ablation. Since lymphatic drainage of the prostate is highly variable, the optimal target volume definition for the pelvic lymph nodes is problematic. To overcome this limitation, we tested the feasibility of an intensity modulated radiation therapy (IMRT) protocol, taking under consideration the individual pelvic sentinel node drainage pattern by SPECT functional imaging. METHODS: Patients with high risk prostate cancer were included. Sentinel nodes (SN) were localised 1.5–3 hours after injection of 250 MBq (99m)Tc-Nanocoll using a double-headed gamma camera with an integrated X-Ray device. All sentinel node localisations were included into the pelvic clinical target volume (CTV). Dose prescriptions were 50.4 Gy (5 × 1.8 Gy / week) to the pelvis and 70.0 Gy (5 × 2.0 Gy / week) to the prostate including the base of seminal vesicles or whole seminal vesicles. Patients were treated with IMRT. Furthermore a theoretical comparison between IMRT and a three-dimensional conformal technique was performed. RESULTS: Since 08/2003 6 patients were treated with this protocol. All patients had detectable sentinel lymph nodes (total 29). 4 of 6 patients showed sentinel node localisations (total 10), that would not have been treated adequately with CT-based planning ('geographical miss') only. The most common localisation for a probable geographical miss was the perirectal area. The comparison between dose-volume-histograms of IMRT- and conventional CT-planning demonstrated clear superiority of IMRT when all sentinel lymph nodes were included. IMRT allowed a significantly better sparing of normal tissue and reduced volumes of small bowel, large bowel and rectum irradiated with critical doses. No gastrointestinal or genitourinary acute toxicity Grade 3 or 4 (RTOG) occurred. CONCLUSION: IMRT based on sentinel lymph node identification is feasible and reduces the probability of a geographical miss. Furthermore, IMRT allows a pronounced sparing of normal tissue irradiation. Thus, the chosen approach will help to increase the curative potential of radiotherapy in high risk prostate cancer patients

Treatment of Stress Urinary Incontinence with Muscle Stem Cells and Stem Cell Components: Chances, Challenges and Future Prospects

Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and the economic burden is substantial. Among the different subtypes of UI, stress urinary incontinence (SUI) is the most prevalent and focus of this review. The main underlying causes for SUI are pregnancy and childbirth, accidents with direct trauma to the pelvis or medical treatments that affect the pelvic floor, such as surgery or irradiation. Conservative approaches for the treatment of SUI are pelvic physiotherapy, behavioral and lifestyle changes, and the use of pessaries. Current surgical treatment options include slings, colposuspensions, bulking agents and artificial urinary sphincters. These treatments have limitations with effectiveness and bear the risk of long-term side effects. Furthermore, surgical options do not treat the underlying pathophysiological causes of SUI. Thus, there is an urgent need for alternative treatments, which are effective, minimally invasive and have only a limited risk for adverse effects. Regenerative medicine is an emerging field, focusing on the repair, replacement or regeneration of human tissues and organs using precursor cells and their components. This article critically reviews recent advances in the therapeutic strategies for the management of SUI and outlines future possibilities and challenges