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Abstract Background Whenever technically feasible and oncologically justified, nephron-sparing surgery is the current standard of care for localized renal cell carcinomas (RCC). The main complications of partial nephrectomy, especially for large and centrally located tumors, are urinary leakage and parenchymal bleeding. We prospectively evaluated the pros and cons of using porcine small intestinal submucosa (SIS, Surgisis®) to close the renal defect after nephron-sparing surgery. Methods We used Surgisis® (Cook medical, Bloomington, IN, USA) to secure and compress the capsular defect after tumor resection in 123 patients submitted to 129 partial nephrectomies between August 2003 and February 2011. Results The median tumor size was 3.7 cm (range 1.1-13.0 cm). Procedures were performed with cold ischemia in 24 cases (18.2%), with warm ischemia in 46 (35.6%), and without ischemia in 59 cases (44.8%). In the total group of patients, 4 (3.1%) developed urinary fistula, and only 2 (1.6%) required postoperative transfusions due to hemorrhage after the application of the small intestinal submucosa membrane. Conclusion Small intestinal submucosa is an easy-to-use biomaterial for preventing complications such as postoperative bleeding and urinary fistula in nephron-sparing surgery, especially in cases where tumor excision causes significant renal capsular and/or renal pelvic defects.

To evaluate the oncological results, associated complications, and postoperative health-related quality of life (HR-QoL) in patients treated with partial cystectomy (PC) for muscle-invasive bladder cancer (MIBC). 27 patients who underwent open PC for cT2 MIBC were included. A simple Cox's proportional hazards regression model was used to assess the association of several potential prognostic factors with survival. Postoperative HR-QoL was assessed with the EORTC (European Organisation for the Research and Treatment of Cancer) QLQ-C30 questionnaire version 3.0. Final pathological tumour stages in PC specimen were: pT0: 18.5%, non-MIBC: 3.7%, MIBC: 74.1%, pCIS: 14.8%. Estimated 5-year overall- and progression-free survival rates were 53.7% and 62.1%. Five (18.5%) patients experienced local recurrence with MIBC. Overall, the salvage cystectomy rate was 18.5%. The 90-day mortality rate was 0%. Significant risk factors for progression-free survival were vascular invasion (HR 5.33) and tumour multilocularity (HR 4.5) in the PC specimen, and a ureteric reimplantation during PC (HR 4.53). The rates of intraoperative complications, 30- and 90-day major complications were 7.4%, respectively and 14.8% for overall long-term complications. Postoperatively, median (IQR) global health status and QoL in our PC cohort was 79.2 (52.1-97.9). Open PC can provide adequate cancer control of MIBC with good HR-QoL in highly selected cases. Open PC can lead to long-term bladder preservation and shows an acceptable rate of severe perioperative complications, even in highly comorbid patients.

Both cholesterol levels and the use of statins have been described to influence the development and prognosis of prostate cancer (PC). In this retrospective, cross-sectional analysis of consecutive cases from a tertiary referral center we evaluated an association between hypercholesterolemia (≥5.0mmol/l), the use of statins, and advanced/aggressive PC in 767 men with histologically confirmed, clinically localized PC awaiting radical prostatectomy. We found that patients with HCE (n=287, 37.4%) had a significantly higher incidence of poorly differentiated PC (Gleason score ≥7b, 81.1% vs. 4.9%), advanced local tumor stage (≥pT3, 57.7% vs. 22.2%), and nodal involvement (19.8% vs. 1.6%). Multivariate logistic regression analysis identified hypercholesterolemia as a risk factor for aggressive and/or advanced PC (OR 2.01, p<0.001) whereas statin intake showed an odds ratio of 0.49 (p=0.005) indicating a negative association with high-risk PC. Despite a limited number of patients using statins (~9.5%), adjusted and weighed multivariate logistic regression models revealed that preoperative hypercholesterolemia is associated with a diagnosis of high-risk PC which is negatively influenced by statin intake.

Purpose: Failure of endocrine treatment in castration-resistant prostate cancer (CRPC) is often associated with the emergence of C-terminally truncated androgen receptor variants that function as constitutively active transcription factors (i.e., AR∆LBD). The mechanisms involved in the regulation of AR∆LBD signaling are largely unknown. Since the IGF-1 pathway was repeatedly shown to affect AR function, we studied whether an inhibition of IGF-1R could also affect AR∆LBD signaling., Methods: Regulation of androgen receptor (AR) and AR∆LBD signaling was analyzed by reporter gene assays, immunoblotting, ELISA and quantitative RT-PCR., Results: Inhibition of IGF-1R with the small-molecule inhibitor NVP-AEW541 reduced the transcriptional activity of the AR and its truncated counterparts Q640X and AR-V7. As shown in Q640X, the inhibition of transcriptional activity was paralleled by a decreased receptor phosphorylation., Conclusions: Inhibition of IGF-1R leads to a down-regulation of AR∆LBD signaling and provides a rationale for CRPC therapies targeting growth factor receptors.

Background: In Germany, testicular cancer accounts for about 1-2% of all malignant tumours. Although, therefore, this is a rare tumour, it assumes an exceptional position among malignant tumours in several respects. In male patients aged 20-35 years it is the most common tumour, which directly affects the family and life planning of young men, a matter of prime importance at this age. Another aspect of testicular cancer is its excellent prognosis since the introduction of platinum-based chemotherapy into the armamentarium of testicular cancer therapy. Therefore, therapeutic innovations increasingly focus on reducing the radicality of treatment, even more so since this therapy, in addition to acute toxicity, can cause severe long-term consequences up to and including secondary malignancies., Objectives: This article gives an overview of the present therapeutic standard of stage I testicular cancer treatment., Material and Methods: Selective PubMed research Results and Discussion: Besides potential implications for organ-sparing surgery, the article elucidates the benefits of a risk-adapted therapeutic approach and indications for a surveillance strategy for patients with localised testicular cancer., (© Georg Thieme Verlag KG Stuttgart · New York.)

Prostate cancer is the most prevalent non-skin cancer and the second leading cause of cancer death in men of the western world. As growth and differentiation of prostate cancer largely depend on androgens, inhibition of the androgen/androgen receptor signaling axis is the main treatment for locally advanced and/or metastatic tumors. Although first-line androgen deprivation therapies like chemical/surgical castration and/or administration of anti-androgens are able to control the disease for several years, prostate cancer almost invariably recurs as castration-resistant prostate cancer. This stage of the disease is characterized by a sustained AR-signaling despite castrate levels of circulating androgens. Various molecular mechanisms were shown to induce castration resistance. This review will discuss the most recent and relevant experimental findings on AR-signaling in castration-resistant prostate cancer in order to provide a comprehensive interpretation of the clinical behavior of this tumor entity following treatments with abiraterone, enzalutamide, ARN-509 or taxanes.

Background: There is evidence that obesity is associated with an aggressive prostate cancer (PC). Furthermore, preclinical studies suggest that oestrogens may play a pivotal role in this context. The biological processes underlying these observations are not fully understood. We prospectively evaluated whether obesity and/or preoperative estradiol levels are associated with high-grade cancer in patients with clinically localized PC at the time they underwent radical retropubic prostatectomy (RRP)., Methods: Preoperative sex hormone serum 17β-estradiol (E2) as well as body mass index (BMI) and waist circumference (WC) were assessed in a cohort of 746 consecutive men treated with RP from February 2011 to October 2014. The data were correlated with patient-specific and clinicopathologic variables., Results: A total of 746 patients underwent RRP. Median age was 68.0 years. Median E2 serum level was 18.3 ng/l (IQR 12.9-24.2 ng/l). Median BMI was 26.6 kg/m(2) (IQR 24.6-29.1 kg/m(2)), and the median WC was 103 cm (IQR 96-110 cm). Serum E2 below or above the normal range was not found more frequently in obese patients (high BMI: p = 0.62; large WC: p = 0.83). E2 was not associated with BMI in our cohort of patients (r = 0.07, p = 0.10) or WC (r = 0.07, p = 0.10). There was no association between preoperative serum E2 levels and tumour stage (p = 0.86, Fisher's exact), tumour grade (p = 0.37), lymph node involvement (p = 0.59) or Gleason score (p = 0.44). However, obesity correlated with tumour stage and grade (p = 0.036, Fisher's exact) and nodal metastasis (p = 0.039, Fishers' exact)., Conclusion: Pretreatment serum 17β-estradiol (E2) cannot be considered as a suitable marker for aggressive tumour disease in patients with localized prostate cancer.

Purpose: The serum C-reactive protein (CRP) level correlates with the clinical prognosis in patients with kidney, penile and metastatic castration-resistant prostate cancer (PC). We prospectively evaluated the preoperative CRP level as a predictive marker for an advanced tumor stage or high-grade cancer in patients with clinically localized PC., Methods: The study evaluated 629 patients with clinically localized PC who underwent radical prostatectomy between 2010 and 2013. Exclusion criteria were signs of systemic infection, symptoms of an autoimmune disease or neoadjuvant androgen deprivation., Results: Poorly differentiated PC tends to be more common in patients with elevated CRP levels (15.5 vs. 9.5%, p = 0.08). Analogously, patients with a Gleason score ≥8 PC had significantly higher median CRP levels than those with a Gleason score ≤7 PC (1.9 vs. 1.2 mg/l, p = 0.03). However, neither uni- nor multivariate analysis showed an association between the preoperative CRP level and the presence of a locally advanced tumor stage, lymph node metastases or a positive surgical margin. CRP also failed to correlate with the initial PSA level and the clinical tumor-associated findings. Moreover, multivariate analysis relativized the association between an elevated CRP level and poor tumor differentiation., Conclusion: In patients with clinically localized PC, CRP does not appear to possess the predictive value and it was shown to have patients with other tumor entities or advanced PC.

Objectives: To evaluate whether low testosterone levels or obesity, or both, are directly associated with tumor stage/grade in patients with clinically localized prostate cancer., Methods: Preoperative androgen serum levels (total and free testosterone), sex hormone-binding globulin, body mass index and waist circumference were assessed in 510 consecutive European Caucasian men treated with radical prostatectomy. Hormone levels and body mass index/waist circumference were correlated with patient- and tumor-specific characteristics using multivariable logistic regression analysis., Results: Even though we confirmed an inverse correlation between bodyweight and testosterone levels, only overweight - but not low testosterone - was associated with advanced disease and poor differentiation of prostate cancer. Using multivariate analyses, both body mass index ≥30 kg/m(2) and waist circumference >110 cm were associated with high-grade disease (Gleason score ≥8). A waist circumference >110 cm also correlated significantly with lymph node metastasis., Conclusions: This is the first study showing that obesity, but not low serum testosterone levels, is significantly associated with high grade and metastatic disease in men diagnosed with clinically localized prostate cancer. The present findings suggest that low androgen levels at diagnosis, which used to be held responsible for the development of aggressive prostate cancer, is only an epiphenomenon of obesity rather than the cause of prostate cancer development and/or progression., (© 2014 The Japanese Urological Association.)

Purpose: To examine whether surgical decompression of hematomas by capsulotomy can help to improve long-term renal function following extracorporeal shock wave lithotripsy (SWL)., Materials and Methods: This study retrospectively identified 7 patients who underwent capsulotomy for post SWL renal hematomas between 2008 and 2012. The control group comprised 8 conservatively treated patients. The median follow-up time was 22 months., Results: The two groups were comparable in age, gender, body mass index, risk factors for developing hematomas (renal failure, urinary flow impairment, indwelling ureteral stent and diabetes mellitus) and the selected SWL modalities. Hematoma size was also similar. However, significantly more patients in the surgical group had purely intracapsular hematomas (85.7% vs. 37.5%) without a potentially pressure-relieving capsular rupture. There were no significant differences in the post-interventional drop in hemoglobin, rise in retention parameters or drop in glomerular filtration rate (GFR). No capsulotomy-related complications were observed, but surgery required a significantly longer hospital stay than conservative management (median, 9 days vs. 5 days). The two groups also showed comparable recovery of renal function at long-term follow-up (median change in GFR from baseline, 97.1% and 97.8%, respectively)., Conclusion: Since renal function did not differ between the two treatment groups, the conservative management remains the standard treatment for post-SWL renal hematoma.

Background: Abiraterone, an androgen synthesis inhibitor, has been successfully used in the treatment of castration-resistant prostate cancer (CRPC) for 2 yr. Enzalutamide is a second-generation nonsteroidal antiandrogen that has recently been approved for the same indication., Objective: This is the first study to evaluate the effectiveness of enzalutamide after failure of abiraterone., Design, Setting, and Participants: Thirty-five patients were identified as having received sequential therapy with abiraterone followed by enzalutamide. All patients had undergone prior docetaxel chemotherapy, and no patient had received ketoconazole., Outcome Measurements and Statistical Analysis: Posttreatment changes in prostate-specific antigen (PSA) were used to determine the activity of enzalutamide in patients who had received prior abiraterone., Results and Limitations: The median duration of abiraterone treatment was 9.0 mo (range: 2.0-19.0 mo). Of the 35 patients, 16 (45.7%) achieved a >50% decline in PSA, and 14 (40%) had a rising PSA as the best response. The median duration of subsequent enzalutamide treatment was 4.9 mo (Kaplan-Meier estimate; 95% confidence interval [CI], 2.4-7.4). Seven of 16 CRPC patients who were initially abiraterone-sensitive (43.8%) and 3 of 19 CRPC patients who were initially abiraterone-insensitive (15.8%) showed a >50% PSA decline while taking enzalutamide. Of the 35 patients, 17 (48.6%) were primarily enzalutamide-resistant and showed a rising PSA as the best response. Median time to progression was 4.0 mo (95% CI, 2.0-6.0) for 18 of 35 patients with at least one declining PSA value while taking enzalutamide (51.4%). Of the 17 patients who were assessable radiologically, only 1 (2.9%) attained a confirmed partial response. Small sample size was the major limitation., Conclusions: Enzalutamide treatment achieved only a modest response rate in patients progressing after abiraterone. Although cross-resistance between abiraterone and enzalutamide was a common phenomenon, it was not inevitable, and a small but significant number of patients showed significant benefit from sequential treatment., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The incidence of muscle-invasive bladder cancer (MIBC) is increasing. Many different and multimodal novel treatment options were brought on the way since the beginning of a new era in the early 1980s, when the neobladder as a common option for urinary diversion had been induced. In addition to open radical cystectomy and urinary diversion, recently, minimal invasive surgery has been implemented in experienced centers and led to promising results in short term follow-up, awaiting confirmation in larger cohorts. Pelvic lymphnode dissection can cure patients with low metastatic load. Expansion of pelvic lymphonodal dissection and its influence on survival was discussed intensively with trends to a moderate enlargement of the standard field. Outcome in nodal positive disease is remaining poor, while 90% of patients with multiple lymphnode metastases will suffer from systemic progress 5 years after diagnosis. In the last decade, treatment regimens based on neoajuvant or adjuvant chemotherapy were published with different results on efficiency. To decide whether to treat with surgery alone, or to offer perioperative systemic cytostatic therapy, is one of the unanswered questions. Furthermore, bladder preserving techniques are still optional for patients with small unifocal lesions or the medically unfit cohort. This review summarizes current data and aims to help guiding through several available recommendations on therapy and management of MIBC.

Background: The nodal status is a strong predictor for cancer specific death in patients with penile carcinoma, and the C-reactive protein (CRP) level at diagnosis has recently been shown to be associated with poor clinical outcome in various solid malignancies. Therefore, this retrospective study was performed to evaluate the association between preoperative CRP levels and the incidence of nodal metastasis in patients with squamous cell carcinoma (SCC) of the penis., Methods: The analysis included 51 penile cancer patients who underwent either radical or partial penectomy for pT1-4 penile cancer between 1990 and 2010. The nodal status was correlated with patient and tumor specific characteristics., Results: Sixteen (31%) patients had lymph node metastasis at the time of penile cancer surgery. Nodal status was associated with tumor stage but did not correlate significantly with tumor grade. In contrast, high presurgical CRP levels were significantly associated with the diagnosis of nodal involvement (p = 0.04). The optimal CRP cut-off value to predict lymph node metastasis was set at 20 mg/l based on ROC analysis., Conclusions: Since a high preoperative serum CRP level was closely correlated with nodal disease, it could be used as an additional marker to help identify patients with penile cancer who may benefit from inguinal lymph node dissection.

Background: High levels of circulating C-reactive protein (CRP) have recently been linked to poor clinical outcome in various malignancies. The aim of this study was to evaluate the prognostic significance of the preoperative serum CRP level in patients with squamous cell carcinoma (SCC) of the penis., Methods: This retrospective analysis included 79 penile cancer patients with information about their serum CRP value prior to surgery who underwent either radical or partial penectomy at two German high-volume centers (Ulm University Medical Center and Hannover Medical School) between 1990 and 2010. They had a median (mean) follow-up of 23 (32) months., Results: A significantly elevated CRP level (>15 vs. ≤ 15 mg/l) was found more often in patients with an advanced tumor stage (≥pT2) (38.9 vs. 11.6%, p=0.007) and in those with nodal disease at diagnosis (50.0 vs. 14.6%, p=0.007). However, high CRP levels were not associated with tumor differentiation (p=0.53). The Kaplan-Meier 5-year cancer-specific survival (CSS) rate was 38.9% for patients with preoperative CRP levels above 15 mg/l and 84.3% for those with lower levels (p=0.001). Applying multivariate analysis and focusing on the subgroup of patients without metastasis at the time of penile surgery, both advanced local tumor stage (≥pT2; HR 8.8, p=0.041) and an elevated CRP value (>15 mg/l; HR 3.3, p=0.043) were identified as independent predictors of poor clinical outcome in patients with penile cancer., Conclusions: A high preoperative serum CRP level was associated with poor survival in patients with penile cancer. If larger patient populations confirm its prognostic value, its routine use could enable better risk stratification and risk-adjusted follow-up of patients with SCC of the penis.

Purpose: To evaluate the clinical value of the pre-treatment calculated free testosterone (fT), total testosterone (tT), sexual hormone-binding globulin (SHBG) and estradiol (E2) levels as potential predictors of pathological stage and grade in patients with clinically localized prostate cancer., Methods: Preoperative sex hormone serum levels were prospectively measured in 137 patients who underwent radical prostatectomy at the University Hospital Ulm from February 2011 to February 2012. We related sex hormone levels to clinicopathologic data including tumour stage, Gleason score and prostate specific antigen (PSA). (Non)parametric statistical tests and receiver operating characteristics (ROC) analyses were performed., Results: Preoperative serum fT levels were significantly associated with advanced disease (pT3-4 and/or pN+; p = 0.047) and lymph node involvement (pN+) (p = 0.027). Patients with low (<0.047 μg/l) vs. normal fT values (≥0.047 μg/l) were associated with higher tumour stage (p = 0.049), positive lymph node status (pN+ , p = 0.038) and advance disease (p = 0.016). Moreover, low tT values (≤0.193 μg/l; p = 0.018) and elevated SHBG levels (>48.4 nmol/l, p = 0.043) correlated with a higher Gleason score. Conversely, E2 levels were not associated with tumour stage or grade. Applying multivariate analysis, unlike tT, SHBG, and E2 levels, low fT levels were a significant independent predictor of advanced disease (relative hazard ratio 3.05, p = 0.028)., Conclusions: Low pre-treatment fT levels were significantly associated with tumour stage and extraprostatic tumour spread and might-in addition or combination with PSA-serve as a useful prognostic parameter for prostate cancer patients prior to radical prostatectomy.

Background: With lower rates of postoperative renal failure, diabetes and cardiovascular disease, partial nephrectomy achieves longer overall survival and equally long tumor-specific survival. It is thus the current gold standard treatment for renal tumors and now also for those ≥ 4 cm in size. The main complications of nephron-sparing surgery, particularly for large and centrally located tumors, are postoperative parenchymal bleeding and urinary fistulas after opening the urinary collecting system (UCS)., Material and Methods: Between August 2003 and April 2012, 76 partial nephrectomies for tumors ≥ 4 cm in size were performed using porcine small intestinal submucosa (SIS, Surgisis®) to close the capsular, renal and in some cases, UCS defects., Results: The median tumor size was 5.0 cm (range 4.0-13.0 cm) and the intervention was performed with warm ischemia in 25 cases (32.8 %), with cold perfusion in 16 cases (21.2 %) and without ischemia in 35 cases (46.0 %). A total of 4 patients (5.5 %) developed postoperative urinary fistulas and 4 (5.5 %) required revision surgery because of significant postoperative bleeding. There were no local infections or allergic reactions to the foreign material., Conclusions: Surgisis® enables a quick and technically uncomplicated closure of the renal defect after partial nephrectomy for tumors. It has the potential to further minimize postoperative bleeding and urinary fistulas and to facilitate the intervention to the extent that nephron-sparing surgery will gain broader acceptance even in patients with tumors ≥4 cm in size.