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Background: Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment. Methods: This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3–4, PSA >20 ng ml −1 or biopsy Gleason score 8–10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment. Results: After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29–88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32–0.80; P =0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21–0.43; P <0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations. Conclusions: In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

Background: The B-cell translocation gene 2 ( BTG2 ) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer. Methods: The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry. Results: We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients. Conclusion: These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.

Purpose To evaluate the possible association between bladder tumor location and the laterality of positive lymph nodes (LN) in a prospectively collected multi-institutional radical cystectomy (RC) series. Methods The study population included 148 node-positive bladder cancer (BC) patients undergoing RC and pelvic lymph node dissection in 2011 without neoadjuvant chemotherapy and without distant metastasis. Tumor location was classified as right, left or bilateral and compared to the laterality of positive pelvic LN. A logistic regression model was used to identify predictors of ipsilaterality of lymphatic spread. Using multivariate Cox regression analyses (median follow-up: 25 months), the effect of the laterality of positive LN on cancer-specific mortality (CSM) was estimated. Results Overall, median 18.5 LN [interquartile range (IQR), 11–27] were removed and 3 LN (IQR 1–5) were positive. There was concordance of tumor location and laterality of positive LN in 82% [95% confidence interval (CI), 76–89]. Patients with unilateral tumors ( n  = 78) harbored exclusively ipsilateral positive LN in 67% (95% CI 56–77). No criteria were found to predict ipsilateral positive LN in patients with unilateral tumors. CSM after 3 years in patients with ipsilateral, contralateral, and bilateral LN metastasis was 41, 67, and 100%, respectively ( p  = 0.042). However, no significant effect of the laterality of positive pelvic LN on CSM could be confirmed in multivariate analyses. Conclusions Our prospective cohort showed a concordance of tumor location and laterality of LN metastasis in BC at RC without any predictive criteria and without any influence on CSM. It is debatable, whether these findings may contribute to a more individualized patient management.

Dietary habits and incidence of prostate cancer (PCa) are very different in several parts of the world. Among the differences between Eastern and Western diets is the greater intake of soy in the Eastern cultures. This might be one factor contributing to a lower incidence of PCa in Asian men. Many studies using PCa cells and animal studies of chemical carcinogenesis have shown that a wide range of dietary compounds have cancer chemopreventive potential. Therefore, the interest in nutrition-based approaches for prevention and treatment of PCa is increasing. We reviewed all experimental preclinical in vitro and in vivo data as well as clinical trials performed with soy isoflavone genistein for prevention and treatment of PCa. The preclinical data for genistein presented in this review show a remarkable efficacy against PCa cells in vitro with molecular targets ranging from cell cycle regulation to induction of apoptosis. In addition, seemingly well-conducted animal experiments support the belief that genistein might have a clinical activity in human cancer therapy. However, it is difficult to make definite statements or conclusions on clinical efficacy of genistein because of the great variability and differences of the study designs, small patient numbers, short treatment duration and lack of a standardized drug formulation. Although some results from these genistein studies seem encouraging, reliable or long-term data on tumor recurrence, disease progression and survival are unknown. The presented data potentially allow recommending patients the use of genistein as in soy products in a preventive setting. However, at present there is no convincing clinical proof or evidence that genistein might be useful in PCa therapy.

Purpose Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. Methods In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. Results cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. Conclusions In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment. This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3-4, PSA >20 ng ml.sup.-1 or biopsy Gleason score 8-10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment. After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29-88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32-0.80; P=0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21-0.43; P<0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations. In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

There are only a few disorders of the female urethra which have to be treated by open urethral surgery, urethral diverticula and urethral strictures. These diseases are rare and subsequently open surgery of the female urethra is also rare. However, these surgical techniques are an important part of the surgical armamentarium in urology, because this is the only method to preserve quality of life of patients concerned. Surgical therapy of urethral diverticula includes well-defined procedures, such as marsupialization and diverticula excision. In contrast, there is no established surgical therapy for female urethral strictures. Several suggestions to solve this problem have been made in recent years and will be presented in this article.

The Rietveld method is one of the most innovative and most important applications in x-ray diffraction and has now, for the first time, been applied to standard-free precise quantitative crystallographic analysis of urinary stones. The capability of the Rietveld method was demonstrated by analysis of a synthetic mixture of five typical urinary stones: whewellite, hydroxylapatite, brushite, struvite, and uric acid, with 20 weight % for each pure component. The quantitative phase analysis (Rietveld method) yielded a mean absolute error of only 1.6% for the weight fractions of the single urinary stone components. The largest error in weight fraction, 2.3%, occurred with hydroxylapatite, caused by the typical insufficient crystallinity. Crystallographic analysis of complex urinary stones with the aid of x-ray diffraction, in combination with a Rietveld structure refinement, is the method of first choice for qualitative and quantitative phase analysis. With this tool, significant changes in weight fractions for recurrent urinary stones can be precisely detected, with therapeutic consequences.

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). 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. 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). 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.

Changes in the methylation pattern in particular gene promoters as well as genetic sequence mutations play an important role in carcinogenesis. Molecular methods like pyrosequencing provide the specific analysis of these epigenetic and genetic modifications. In this review the relevance of these alterations for prostate cancer and the function of pyrosequencing will be described and explained on the basis of a search of the PubMed literature database. At present, in uro-oncology only a few studies outlining methylation in prostate cancer and pyrosequencing have been published. Nevertheless, it becomes evident that epigenetic mechanisms as well as specific gene sequence alterations have an impact on the carcinogenesis of prostate cancer and knowledge of these factors might open perspectives in diagnostic approaches of the future.