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Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht.

Introduction: Understanding the topographical distribution of prostate cancer (PCa) foci is necessary to optimize the biopsy strategy. This study was done to develop a technical approach that facilitates the analysis of the topographical distribution of PCa foci and related pathological findings (i.e., Gleason score and foci dimensions) in prostatectomy specimens., Material & Methods: The topographical distribution of PCa foci and related pathologic evaluations were documented using the cMDX documentation system. The project was performed in three steps. First, we analyzed the document architecture of cMDX, including textual and graphical information. Second, we developed a data model supporting the topographic analysis of PCa foci and related pathologic parameters. Finally, we retrospectively evaluated the analysis model in 168 consecutive prostatectomy specimens of men diagnosed with PCa who underwent total prostate removal. The distribution of PCa foci were analyzed and visualized in a heat map. The color depth of the heat map was reduced to 6 colors representing the PCa foci frequencies, using an image posterization effect. We randomly defined 9 regions in which the frequency of PCa foci and related pathologic findings were estimated., Results: Evaluation of the spatial distribution of tumor foci according to Gleason score was enabled by using a filter function for the score, as defined by the user. PCa foci with Gleason score (Gls) 6 were identified in 67.3% of the patients, of which 55 (48.2%) also had PCa foci with Gls between 7 and 10. Of 1173 PCa foci, 557 had Gls 6, whereas 616 PCa foci had Gls>6. PCa foci with Gls 6 were mostly concentrated in the posterior part of the peripheral zone of the prostate, whereas PCa foci with Gls>6 extended toward the basal and anterior parts of the prostate. The mean size of PCa foci with Gls 6 was significantly lower than that of PCa with Gls>6 (P<0.0001)., Conclusion: The cMDX-based technical approach facilitates analysis of the topographical distribution of PCa foci and related pathologic findings in prostatectomy specimens., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: The effect of adjuvant radiation therapy on survival in sarcomatoid renal cell carcinoma (sRCC) with no evidence of distant metastasis remains unclear., Methods: Subjects diagnosed with non-metastatic sRCC were identified using the Surveillance Epidemiology and End Results (SEER) (2004-2012) database and divided into groups based on their surgical treatment (ST): no surgery or radiation therapy (NSR); partial nephrectomy (PNE); radical nephrectomy with ureterectomy and bladder cuff resection (RNE + UE + BLAD); and radical nephrectomy (RNE). Certain radical nephrectomy cases also received adjuvant external-beam radiation therapy (RNE + RAD). The Kaplan-Meier method was used to estimate overall survival (OS). A multivariable competing risks regression analysis was used to calculate disease-specific survival (DSS) probability and to determine factors associated with cause-specific mortality (CSM)., Results: A total of 408 patients were included in this study. The 5-year OS and predicted DSS were significantly higher in the patients who underwent STs (i.e., PNE, RNE + UE + BLAD, RNE, and RNE + RAD) (20.1-54.0 and 20.1-59.9 %, respectively) than in the NSR group (9.0 and 11.6 %, respectively) (P < 0.001). ST was independently associated with a decreased CSM (P < 0.0001). No significant differences in OS or the 1-, 3-, or 5-year DSS probabilities between the RNE and RNE + RAD groups were observed. RNE + RAD was not significantly associated with a decrease in 1-year CSM [subhazard ratio (SHR) 0.95; 95 % CI 0.23-3.96; P = 0.947]., Conclusions: Adjuvant external-beam radiation therapy did not increase OS in non-metastatic sRCC patients.

Retroperitoneal schwannomas are a rare entity. They originate from the Schwann cells of the nerve sheaths and may be of renal or pararenal origin. We report on two patients with retroperitoneal schwannomas, who received surgery under the suspicion of renal cell carcinoma.

Introduction: The German Research Activities on Natural Urologicals (GRANU) study was a randomized, partially blinded, placebo-controlled, parallel-group trial that investigated the efficacy of pumpkin seed in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS)., Subjects and Methods: A total of 1,431 men (50-80 years) with BPH/LUTS were randomly assigned to either pumpkin seed (5 g b.i.d.), capsules with pumpkin seed extract (500 mg b.i.d.) or matching placebo. The primary response criterion was a decrease in International Prostate Symptom Score (IPSS) of ≥5 points from baseline after 12 months. Secondary outcome measures included IPSS-related quality of life, IPSS single items and diary-recorded nocturia., Results: After 12 months, the response rate (intention-to-treat/last-observation-carried-forward approach) did not differ between pumpkin seed extract and placebo. In the case of pumpkin seed (responders: 58.5%), the difference compared with placebo (responders: 47.3%) was descriptively significant. The study products were well tolerated. Overall, in men with BPH, 12 months of treatment with pumpkin seed led to a clinically relevant reduction in IPSS compared with placebo., Conclusion: In order to fully justify a recommendation for the use of pumpkin seed to treat moderate LUTS, these findings need to be substantiated in a confirmatory study or systematic review., (2014 S. Karger AG, Basel)

Aim: The present clinical investigation was performed to evaluate the benefits of complementary medicine in prostate cancer patients undergoing hormone therapy (HT)., Patients and Methods: Patients (N=93) were treated according to international guidelines. All patients suffered from side-effects induced by the HT. To reduce the side-effects, the patients were complementarily treated with a combination of sodium selenite, proteolytic plant enzymes and Lens culinaris (Lc) lectin. On case report formulas (CRFs), self assessment of defined side-effects of HT (arthralgia, mucosal dryness, bone pain and hot flushes) were documented before (T-0) and on days 25 (T-1) and 50 (T-2) after complementary treatment. Validation was carried-out by scoring from 1 (no side-effects/optimal tolerability) to 6 (extreme side-effects/extremely bad tolerability), however, only patients suffering from severe side-effects (symptom scores >3) were enrolled in this investigation., Results: The severity of side-effects of HT was reduced by complementary treatment with sodium selenite, proteolytic plant enzymes and Lc-lectin. The mean scores of side-effects declined for arthralgia from 4.72 (T-0) to 3.66 (T-1) to 2.76 (T-2), for mucosal dryness from 4.45 (T-0) to 3.65 (T-1) to 2.90 (T-2), for bone pain from 4.74 (T-0) to 3.44 (T-1) to 2.82 (T-2), for hot flushes from 4.97 (T-0) to 3.70 (T-1) to 3.15 (T-2). The reduced severity of the side-effects was statistically significant (p<0.001) for T-1 and T-2, compared to T-0., Conclusion: This investigation demonstrates benefits of indication-based complementary treatment with the combination of sodium selenite, proteolytic plant enzymes and Lc-lectin in prostate cancer patients, e.g. reduction of side-effects of HT., (Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aims: Long-term urodynamics are required because bladder-emptying disorders are often not clearly revealed by conventional urodynamics. Patients with severe clinical overactive bladder symptoms, for instance, often show normal results. This may be due to the short evaluation time and psychological factors that complicate conventional urodynamics. This study aimed to develop an ambulatory three-component urodynamic measurement system that is easy to operate, registers urodynamic parameters for several days, and has no negative impact on the patient., Methods: We developed an intravesical capsule combined with a hand-held device to register voiding desire and micturition, and an alarm pad device that detects urine loss. Recently, the intravesical capsule and its proven function were detailed in the literature. Here, we present detailed in vitro results using a female bladder model. The flexible capsule was C-shaped to minimize the risk of expulsion from the bladder during micturition. Results of biocompatibility evaluation of the intravesical capsule, which is called Wille Capsule (WiCa) are described., Results: The WiCa with an oval nose and a maximum outer diameter of 5.5 mm was easily inserted through a 25-French cystoscope. Removing the WiCa by grasping the nose using the female model with bladder was easily conducted. Expulsion of the WiCa during voiding was avoided through a novel C-shaped device design. Based on in vitro cytotoxicity studies, the capsule is a promising and safe device., Conclusion: Our novel system is an innovative minimally-invasive tool for accurate long-term urodynamic measurement, and does not require inserting a transurethral catheter.

Introduction: The objective of this study was to determine whether the responses to the same questionnaire differ between women living in a large city and women living in a rural area., Methods: We evaluated the medical records of 88 patients living in the large city of Cologne and of 86 patients living in Brühl and its surrounding rural regions. The responses on the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) of 88 patients who suffer from urinary incontinence and live in a large city were compared to the responses 86 patients who live the rural region of Brühl. In addition, ages, frequency of micturition, use of pads, prior and desired treatment were compared. Limitations of this study include its retrospective study design and the absence of sociodemographic data. Furthermore, the use of a pad test could objectify the extent of incontinence., Results: On average, patients from Cologne used of 6.2 pads and patients from Brühl used 3 pads. Patients from the large city scored 14 out of 21 points on the ICIQ-SF, and women from Brühl scored 11 out of 21 points. This difference was significant. Patients from Cologne had received medicinal treatment or physical therapy significantly more often., Conclusion: The results suggest that urinary incontinence is perceived as a greater impairment by patients residing in (large) cities compared to patients residing in rural areas. An urban-rural gradient in patients with urinary incontinence can be described.

Objective: The aim of the analysis was to measure the pressure-flow urodynamic changes following GreenLight(™) laser vaporization of the prostate based on pressure-flow studies., Material and Methods: Sixty-two patients suffering from voiding dysfunction due to lower urinary tract symptoms underwent potassium titanyl phosphate (KTP) laser vaporization. A pressure-flow study was performed at baseline and at 3 months postoperatively. Symptoms and quality of life (QoL) were assessed using the International Prostate Symptom Score (IPSS) and questions regarding sexuality were assessed using the International Index of Erectile Function (IIEF)., Results: IPSS and QoL scores changed from 24 and 5 at baseline to 6 and 2 at 3 months, respectively. The initial median prostate volume was 35 ml (range 16-60 ml), the median maximum uroflow (Q max) was 9.2 ml/s (4-14.9 ml/s) and the median postvoiding residual urine was 80 ml (20-400 ml) (95% confidence interval 89.14, 135.44). The median IPSS and QoL score were significantly improved (p < 0.001). There was a significant decrease in median detrusor pressure at Q max from 83.1 to 40.45 cmH2O, and the median obstruction grade according to Schäfer's classification was also decreased significantly, from 4 to 1 postoperatively., Conclusion: This study showed that significant deobstruction can be demonstrated using a pressure-flow study at 3 months postoperatively.

To provide sufficient clinical data for corresponding specimens from diverse databases established before the implementation of biobanks for research purposes with respect to data privacy regulations. For this purpose, we developed a data model called "linkage of data from diverse data sources (LDS)". The data model was developed to merge clinical data from an existing local database with biospecimen repository data in our serum bank for uro-oncology. This concept combines two data models based on XML: the first stores information required to connect multiple data sources and retrieve clinical data, and the second provides a data architecture to acquire clinical and repository data. All data were anonymized and encrypted using the Advanced Encryption Standard. X.509 certificates were applied to secure data access. Furthermore, we tested the feasibility of implementing these models in the information management system for biobanking. The data concept can provide clinical and repository data of biospecimens. Only authorized receivers can access these data. Sensitive and personal data are not accessible by the data receivers. The data receiver cannot backtrack to the individual donor using the data model. The acquired data can be converted into a text file format supported by familiar statistical software. Supplementary tools were implemented to generate and view XML documents based on these data models. This data model provides an effective approach to distribute clinical and repository data from different data sources to enable data analysis compliant with data privacy regulations.

NF-κB signal transduction is a potential therapeutic target in many malignant tumors. We have recently shown, in malignant renal proximal tumor cells, that a transcription complex, consisting of NF-κB p65 and mitogen-activated protein kinase p38α, joined by protein kinase C (PKC) α, transmigrates into the nucleus. There, PKCα suppresses the nuclear release of primary microRNA (pri-miRNA) 15a. Induced by endothelin (ET)-1, a decrease in PKCα levels leads to increased miRNA 15a (miR-15A) expression. An identical system can be identified in renal carcinomas, in which, after nuclear transmigration, PKCα binds directly to pri-miRNA 15a in the nucleus. However, the pattern of PKC isoforms differs between malignant renal cell carcinoma (RCC) and benign oncocytoma. PKCα, a component of the transcription complex in tumors, is up-regulated in benign oncocytoma but down-regulated in RCC. Conversely, miRNA 15a is up-regulated in RCC and down-regulated in oncocytoma. A similar behavior is observed in chromophobe carcinoma, whereas differences are less pronounced in papillary RCC (type I): NF-κB target gene expression (ie, ET-1, ET-A and ET-B receptors, vascular cell adhesion molecule-1, IL-6, and fractalkine) is particularly high in malignant RCCs. Up-regulated miRNA 15a can be measured in urine from patients with RCC but is nearly undetectable in oncocytoma, other tumors, and urinary tract inflammation. Thus, the up-regulation of miRNA 15a may be an important marker to help identify malignant clear-cell RCCs in both biopsy and urine samples., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objectives: In order to improve the efficacy of targeted therapy trials, the expression profiles of several molecular markers that are potential candidates for targeted therapy were analyzed in patients with progressive castration-resistant prostate cancer., Methods and Materials: Paraffin-embedded samples of tumor tissue from 51 patients obtained from biopsies of metastases or remaining prostates were analyzed immunohistochemically for the expression of EGFR, PDGFRβ, Her-2/neu, c-Kit, and VEGF. Staining was analyzed according to the percentage of positively stained tumor cells and the intensity of staining., Results: According to the different cut-off values of 10%, 30%, 50%, or 70% for the percentage of positively stained cells, different rates of expression were found. Expression rates ranged from 30.6% to 61.2% for EGFR, from 34.7% to 57.1% for PDGFRβ, from 9.6% to 28.8% for Her-2/neu, from 12.5% to 22.4% for c-Kit, and from 51.1% to 74.5% for VEGF. Defining positive expression as ≥ 30% positively stained tumor cells, with an intensity of staining of ≥ 2+, resulted in positive expression of EGFR in 38.8%, PDGFRβ in 24.5%, Her-2/neu in 13.5%, c-Kit in 6.4%, and VEGF in 44.7% of the patients., Conclusions: Our results demonstrate simultaneous expression of several markers in castration-resistant prostate cancer tissue. Translation of the results into modern, multi-arm clinical trial designs will improve the efficacy of recruiting and obtaining results, compared with multiple double-arm trials., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Ephrin (Eph) receptors are receptor tyrosine kinases; both EphrinB2, as a ligand, and EphB4, as a receptor, are involved in angiogenesis. EphrinB2 is expressed on arteries and EphB4, a specific receptor for EphrinB2, is expressed on veins. It is unknown whether involvement of arteries and veins in tumor angiogenesis is distinctive. Here we investigated their distribution in normal and malignant tissue of the urogenital tract., Materials and Methods: Five-micrometer-thick paraffin sections from nontumoral and tumoral tissues of kidney (n = 12), bladder (n = 33), and prostate (n = 20) were immunoreacted with antisera against EphB4 and EphrinB2 using the avidin-biotin-peroxidase complex technique. Comparisons of EphB4 and EphrinB2 stained arterial and venous vessels in the nontumoral and tumoral sections were evaluated in a semiquantitative analysis as frequency of the vessels in a predetermined tumor area counted under light microscopy., Results: Expression of EphrinB2 in arterial and EphB4 in venous endothelium was significantly greater in tumoral sections compared with nontumoral sections. No statistically significant correlation in comparing the labeling patterns for EphrinB2 with the labeling patterns for EphB4 was observed in nontumoral as well as tumoral sections., Conclusions: The high expression of EphrinB2 in arterial and EphB4 in venous endothelium of urogenital tract tumors might contribute to their involvement in the progression of tumor angiogenesis. The relation between arteries and veins in the normal and tumor tissues is unchanged., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Ibandronate, one of the most potent bisphosphonates, has been shown to inhibit growth of various cancer cell lines. In contrast, little is known about the effects of ibandronate on prostate cancer cells. Therefore the aim of our study was to characterize the effects of ibandronate alone and in combination with docetaxel on the growth of prostate cancer cell lines and to identify the underlying signalling pathways. Material and methods. The prostate cancer cell lines LNCaP and PC-3 were treated with increasing concentrations of ibandronate and docetaxel alone and in combination. Viable cell number was measured after five days using a hemocytometer and the MTT-method. The effects of ibandronate were tentatively antagonized by addition of farnesyl-pyrophosphate (FPP) or farnesol (FOH). Results. Ibandronate inhibits growth of both prostate cancer cell lines in a dose dependent manner. In combination with docetaxel, synergistic effects are found as evidenced by a combination index (CI) of <1. Addition of FOH and FPP completely antagonized the growth inhibitory effects of ibandronate on both cell lines. Surprisingly, in combination with ibandronate and docetaxel, FOH further increased growth inhibition instead of antagonizing the growth inhibitory effects of ibandronate. Furthermore, FOH alone appeared to be a potent inhibitor of tumor cell growth. Discussion. Ibandronate effectively inhibits growth of prostate cancer cell lines via inhibition of the farnesyl-IPP-synthase and exhibits synergistic effects with docetaxel. In addition, FOH is a potent inhibitor of prostate cancer cell lines and may display an interesting treatment option for patients with CRPC.

Neonatal testicular infarction is a rare occurrence. We report on a newborn infant with bilateral testicular infarction. At birth, the uncut umbilical cord ran taut between the thighs making a complete loop around the genitals, compressing the testes. At the age of 6 hours, because of increasing agitation and the beginnings of scrotal discoloration, the infant was operated on, showing a bilateral testicular infarction potentially induced by strangulation of the twisted umbilical cord. Here, we discuss the clinical findings of neonatal testicular infarction and give advice as to the management of this serious complication with regard to the available published data., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Many scientists of varying clinical backgrounds have described the phenomenon of spermaturia in animals, adolescents as well as fertile and infertile men. Nevertheless, research for an expert opinion on a law case in the field of forensic medicine revealed a lack of valid information about the longevity of spermatozoa in post-ejaculatory urine (PEU) of fertile men. Our goal was to measure the appearance of vivid sperm in PEU while considering the factor of time in order to predict a realistic interval, in which positive sperm findings might occur. Therefore ten healthy, young men donated their sperm for fertility analysis and a urine sample prior to and after ejaculation. The time intervals between ejaculation and the first micturition were preset ranging between 30 min and maximal 11h. Each ejaculate underwent a semen analysis. The pre- and post-ejaculatory urine samples were screened for the presence of viable and motile spermatozoa. Semen parameters were determined and related to the sperm findings in the precipitate of the urine samples. The amount, the viability and motility status of the detected spermatozoa were recorded after each preset time interval. The results showed that none of the 10 participants had sperm in their urine samples prior to ejaculation. The average sperm concentration was 50.1+/-25.8 million/ml. After a time span of 30 min 59.5% of the first fractions of PEU samples were sperm positive, after 2 and 4h still 70%, and after 5h sperm were no longer detected. The last motile spermatozoa could be found after 4.5h. It seems that remaining sperm in the urethra are washed out with the first micturition in the majority of fertile men, however, the conclusion as to whether sperm findings >5h after ejaculation are improbable needs to be confirmed by further investigations., (2009 Elsevier Ireland Ltd. All rights reserved.)

Aim: To test the hypothesis that sildenafil (50 mg nightly for one year) can improve spontaneous erectile function (EF) in men with mild-to-moderate arteriogenic erectile dysfunction (ED) responsive to erectogenic treatment., Methods: In a prospective open-label trial, 112 men with ED were randomized to sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months, followed by one-month and 6-month non-medicated periods. Non-randomized, non-medicated men with ED were also assessed. The EF domain of the International Index of Erectile Function (IIEF EF) and the peak systolic velocity (PSV) of penile cavernous arteries were used to measure the efficacy., Results: After sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in 29 of 48 (60.4%, 95% confidence interval [CI]: 45.3-74.2%) of the nightly group vs. 4 of 49 (8.2%, 95% CI: 2.3-19.6%) of the as-needed group. PSV improved by 11.2 cm/s (95% CI: 4.7-21.4; P=0.012) in the nightly group but only by 3.4 cm/s (-5.1-14.7; P=0.435) in the as-needed group. IIEF EF normalized in 1 of 18 (5.6%, 95% CI: 0.1-27.3%) non-medicated men and the PSV declined slightly. Six months after treatment, the IIEF EF remained normal and PSV was stabilized in most (28/29, 97%) nightly group men who had initially normalized., Conclusion: Sildenafil nightly for one year resulted in ED regression that persisted well beyond the end of treatment, so that spontaneous EF was characterized as normal on the IIEF in most men. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.

In an open-label extension of a randomized, double-blind clinical trial, the long-term efficacy and tolerability of a fixed combination of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule (PRO 160/120) were investigated in elderly men with moderate or severe lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). Two hundred and fifty-seven patients were randomly treated with 2 x 1 capsule/day PRO 160/120 or placebo for 24 weeks, followed by a 24-week control period and a 48-week follow-up period in which all patients received PRO 160/120. Efficacy measures included the assessment of LUTS [International Prostate Symptom Score ((I-PSS) self-rating questionnaire] and uroflow and sonographic parameters. Two hundred and nineteen subjects participated in the follow-up. Between baseline and end of observation (week 96) the I-PSS total score was reduced by 53% (P < 0.001), peak and average urinary flow increased by 19% (P < 0.001), and residual urine volume decreased by 44% (P = 0.03). The incidence of adverse events during follow-up was one in 1,181 treatment days; in only one event a causal relationship with intake of PRO 160/120 could not be excluded. Treatment with PRO 160/120 thus provides a clinically relevant benefit over a period of 96 weeks.

Objectives: Radical nephrectomy displays the standard procedure for patients with localized renal cell carcinoma. The transperitoneal approach is often favored compared to the retroperitoneal approach because of the early ligation of the renal vessels, thereby tumor cell shedding by manipulation of the tumor is thought to be avoided. The aim of our study was to investigate the influence of the surgical technique on intraoperative tumor cell shedding. Furthermore, we evaluated the clinical course of the patients being operated on with either method in terms of complications, postoperative recovery, and hospital stay., Methods: A total of 55 consecutive patients with renal tumors suspicious for malignancies were evaluated for this study. Peripheral blood samples were obtained from 44 patients at admission, intraoperatively (before and after kidney removal), and before discharge. Ribonucleic acid was extracted, converted to complementary deoxyribonucleic acid, and reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for G250/MNCA-9 was performed. Data regarding the clinical course of the patients were analyzed retrospectively by reviewing patient files., Results: The clinical course for patients undergoing retroperitoneal nephrectomy was statistically different compared to the transperitoneal approach group regarding operating time and duration of drains, favoring the retroperitoneal approach group. Evaluation of MNCA-9 RT-PCR revealed no difference according to operative technique, tumor-nodes-metastasis, or clinical tumor stage. Despite this result, we found positive RT-PCR signals for MNCA-9 in patients with transitional cell cancer of the renal pelvis and benign renal lesions., Conclusions: There is no clinical relevant difference between the transperitoneal and retroperitoneal approaches for radical nephrectomy. Furthermore, the retroperitoneal approach does not bear the risk of intraoperative tumor cell shedding by the handling of the tumor.

The aim of this prospective, randomized, double-blind, double-dummy, multicenter clinical trial was to investigate the efficacy and safety of PRO 160/120 (Prostagutt forte), a fixed combination preparation of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule, in comparison to the alpha1-adrenoceptor antagonist tamsulosin (CAS 106463-17-6) in lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). 140 elderly out-patients suffering from LUTS caused by BPH, with an initial score > or = 13 points in the International Prostate Symptom Score (I-PSS), received 2 x 1 capsule/d PRO 160/120 or 1 x 0.4 mg/d tamsulosin and were treated for 60 weeks with interim visits at weeks 8, 16, 24, 36, and 48. The primary outcome measure for efficacy was the change in I-PSS total score, the percentage of patients with an I-PSS score < or = 7 points at endpoint ('responders') was analyzed as well. During 60 weeks of randomized treatment the I-PSS total score was reduced by a median of 9 points in both groups. In total, 32.4 % of the patients in the PRO 160/120 group and 27.9% in the tamsulosin group were responders (test for non-inferiority of PRO 160/120: p = 0.034; non-inferiority margin 10%). Both drugs were well tolerated, with one adverse event in 1514 treatment days for PRO 160/120 and one event in 1164 days for tamsulosin. The study supports non-inferiority of PRO 160/120 in comparison to tamsulosin in the treatment of LUTS caused by BPH.

Objectives: Some men with erectile dysfunction (ED) have difficulties discussing their condition with their physicians. Existing screening and diagnostic tools for ED often require the administration of personal questions regarding the condition. We present a simple risk score to estimate the individual likelihood of somatic ED, based on age and existing health conditions., Methods: Data from the Cologne Male Survey (n = 4396) were used to develop a multivariable logistic regression model for the individual ED likelihood. The regression equation was both internally and externally validated using data from a national study (Berlin study) and a multinational cross-sectional study (MALES study)., Results: A final regression equation including age, pelvic surgery, diabetes mellitus, arterial circulatory disorder, heart disease, smoking, and hypertension reached an area under the receiver operating characteristic curve of 0.84 (0.5 means random and 1.0 perfect discrimination). Internal validation did not indicate any relevant overfit and the external validation results (national data: AUC = 0.75; multinational data: AUC = 0.67) are similar to those of other popular risk scores., Conclusions: The validated ED risk score developed from the regression equation can be used as a screening tool to identify patients who are at a high risk of somatic ED. This tool can facilitate entering into discussions between physicians and patients regarding erectile function.

Objectives: To define the anti-angiogenic mechanism and causes of the heterogeneous influence of endostatin, one of a group of matrix-derived inhibitors of tumour angiogenesis of increasing significance in tumour treatment, on various tissue types., Materials and Methods: Variations in the binding behaviour of endostatin with vessels were assessed in different tumours (bladder, prostate and kidney) and compared with benign tissue vessels. Biotinylated endostatin was used and detected using extravidin CY3 and extravidin-gold immunolabelling., Results: There were significant differences in the number of vessels showing endostatin binding among benign and malignant bladder, prostate and kidney tissues. While there was distinct endostatin binding on a mean (sd) of 94.2 (3.0)% bladder and 73.8 (19.5)% prostate tumour vessels, there was less binding, at 11.32 (3.9)%, on kidney tumour vessels. There was less binding to vessels of benign bladder, prostate and kidney tissue, at 2.0 (1.5), 1.7 (1.7) and 1.5 (1.7)%, respectively. At the ultrastructural level, different binding sites were detected both inside and outside the endothelial cells., Conclusion: Endostatin binds more to all tumour tissues than to benign tissue, but the degree of binding in malignant kidney tissue was significantly less than that in malignant prostate and bladder tissues. These divergent vascular endostatin-binding patterns could be responsible for a tumour type-dependent anti-angiogenic effect attributable to endostatin. Such selective behaviour would have therapeutic consequences for future anti-angiogenic therapy, in which different kinds of tumours could be further classified into those responding to endostatin or not.

Objective: The angiogenic phenotype is an effect of a net balance of angiogenic and anti-angiogenic factors. Endostatin is one of a group of recently described matrix-derived inhibitors of tumour angiogenesis that have acquired increasing significance for tumour treatment. Endostatin's anti-angiogenic mechanism and the causes of its heterogenic influence on various tissue types have not yet been defined., Methods: We investigated the variations in endostatin's binding behaviour to vessels in benign prostatic hyperplasia (BPH) compared to endostatin binding to vessels in normal prostate tissue. Biotinylated endostatin was used and was detected using Extravidin CY3., Results: In BPH 89.12% +/- 10.72% of vessels showed endostatin binding. This was significantly more than observed for vessels in normal prostate tissue (1.66% +/- 1.66%)., Conclusion: The strongly proliferative tissue of BPH may be a growth-limited cause of significantly more endostatin binding sites. The investigation indicates endostatin as a possible new target for BPH treatment.

Background: Liposomal encapsulation of doxorubicin has been shown to reduce nonspecific delivery of this agent to normal tissue and to increase specific delivery to malignant cells. On the basis of doxorubicin's demonstrated clinical efficacy against hormone-refractory prostate carcinoma (HRPCA), the authors conducted a prospective, randomized Phase II clinical trial to evaluate the feasibility, toxicity, and therapeutic efficacy associated with the pegylated form of this agent., Methods: Forty-eight patients with symptomatic HRPCA were randomized to receive pegylated liposomal doxorubicin at either 25 mg/m2 every 2 weeks for 12 cycles (Group A) or 50 mg/m2 every 4 weeks for 6 cycles (Group B). Thirty-eight of these 48 patients (79%) presented with severe pain (corresponding to a pain score of 7.5 on a visual analog scale [VAS] ranging from 0 to 10) due to osseous metastases. Therapeutic efficacy was assessed by serial evaluation of serum prostate-specific antigen (PSA) concentrations and by serial measurement of pain levels (using a VAS ranging from 0 to 10). Toxicity data were obtained using the National Cancer Institute of Canada/Cancer and Leukemia Group B criteria and the 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire., Results: The median patient age was 68.9 years (range, 58-79 years), and the mean follow-up duration was 42 months. The mean pretreatment PSA level was 660.4 ng/mL (mean, 8-6340 ng/mL); an objective decrease in PSA levels (i.e., a decrease of > 50%) was observed in 8 of 31 patients (25.8%) in Group B, whereas no other patient in either group experienced such a decrease. The mean time to disease progression was 6.5 months, and the mean survival duration was 13.4 months. Patients in Group B had a significantly higher rate of response with respect to pain (52.6% vs. 28.6%; P = 0.04), and the mean 1-year survival rate also was significantly higher in Group B (42% vs. 15%; P = 0.02). Severe side effects were observed, with 24 patients (50%) experiencing World Health Organization Grade 3/4 toxicity. Toxicity types differed significantly between Group A and Group B; palmar-plantar erythrodysesthesia developed in 60% of patients in the former group (P < 0.0005), whereas tachycardia was more common in the latter group (39% of patients; P < 0.0005). No dose-limiting cardiotoxicities or hematotoxicities were documented., Conclusions: Pegylated liposomal doxorubicin yielded a noteworthy objective palliative response rate and a mean survival of 13 months for patients with symptomatic HRPCA. The dosage tested in the current study should be used in future Phase II and Phase III trials of pegylated liposomal doxorubicin-containing combination regimens for patients with HRPCA., (Copyright 2004 American Cancer Society.)

The prevalence of erectile dysfunction (ED) has dramatically increased in parallel with the aging of the Western industrialised population. The estimated prevalence of ED worldwide in 1995 was 152 million men. As the population in industrial nations ages, an estimated 322 million men will be affected by ED by the year 2025. Oral drug therapy with the phosphodiesterase (PDE) type 5 inhibitor sildenafil fails in some patients with ED; however, several different classes of drugs demonstrate efficacy in treating ED, creating the potential for pharmacological combination therapy. Pharmaceutical products that lead to the activation of or an increase in cyclic nucleotides (cyclic adenosine monophosphate and cyclic guanosine monophosphate), with or without nitric oxide donors or nitrates, as well as alpha-adrenoceptor antagonists, have been used to treat ED. Sildenafil has been used in combination with alprostadil (prostaglandin E1) and administered via intraurethral or intracavernous route. Successful intercourse using this combination of agents varies from 47% to 100% following failed monotherapy. Various combination therapies for ED are being studied using PDE5 inhibitors, together with other agents, alpha-adrenoceptor antagonists, and testosterone replacement therapy for men with hypogonadism. The combination of centrally acting agents with PDE5 inhibitors, e.g. a regimen of apomorphine plus PDE5 inhibitor, is an attractive approach because the two therapies target different mechanisms. New PDE5 inhibitors such as vardenafil should be tried first as therapy for sildenafil nonresponders before exploring any combination therapy options. Preliminary observations of combination therapy have been encouraging and provide a scientific rationale for prospective, randomised clinical trials with adequate numbers of patients.

Background: Nitric oxide (NO) is produced by a group of synthase enzymes (NOS). By means of different pathways, NO exerts several functions in benign and malignant human bladder tissues. The current paper describes the NO/guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) and the NO/oxidative pathways in human bladder tissues., Methods: Bladder carcinoma tissues were collected from 18 patients by transurethral resection procedures. Normal benign vesical tissue specimens from a further eight patients with benign diseases served as controls. Immunohistochemistry was conducted for localization of sGC, cGMP, and nitrotyrosine in benign and malignant vesical tissues, evaluating two-three tissue sections per patient., Results: Positive immunolabeling for sGC and cGMP was detected in vascular endothelial cells of normal and malignant vesical tissues. Those signals were most intense in bladder carcinoma tissues. Immunolabeling for sGC and cGMP was also detected in normal urothelial cells. In bladder carcinoma cells, a heterogeneous immunolabeling for sGC and cGMP was seen, with a wide spectrum of signal intensity. Positive immunostaining for sGC and cGMP was also observed in stromal round cells in benign and malignant bladder tissues. Immunolabeling for nitrotyrosine was mainly observed in endothelial cells, with a much stronger immunolabeling in bladder carcinoma tissues compared to normal benign controls. A weak immunolabeling for nitrotyrosine was also observed in bladder carcinoma cells. Normal urothelial cells did not show such nitrotyrosine expression., Conclusions: The current report provides evidences that NO play several roles through different pathways in benign and malignant vesical tissues. The influences generated by NO molecules can be divided into cGMP-mediated effects (those resulting from the NO/sGC/cGMP pathway) and non-cGMP-mediated effects (those resulting from the NO/oxidative pathway). Increased angiogenesis is a cGMP-mediated effect, while nitrotyrosine production is a non cGMP-mediated oxidative effect. Such an NO/oxidative pathway is observed more often in bladder carcinoma., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10942)

Bayer is developing vardenafil, an orally active phosphodiesterase (PDE) 5 inhibitor for the potential treatment of erectile dysfunction (ED) [314382]. NDAs were filed in September 2001 in the US and Mexico [423096], and vardenafil was submitted for Canadian approval in October 2001. As of November 2001, Bayer was expecting a response from the FDA in the second half of 2002 [429499]; the EMEA accepted a filing in January 2002, following a December 2001 submission [438163]. By October 2000, phase III trials were underway in Japan [384751] and by December 2001, a Japanese NDA had been filed; at the same time an application was filed in South Africa [426526], [433060]. At this time Japanese launch was expected in 2003 [434758]. By February 2001, Bayer was also investigating a nasal formulation of vardenafil for the potential treatment of erectile dysfunction [397608]. In November 2001, Bayer and GlaxoSmithKline signed a worldwide copromotion agreement for vardenafil, under which Bayer was to be responsible for all regulatory work required to obtain approval [429499]. In February 1999, Lehman Brothers predicted a 10% probability that vardenafil would reach the market, with launch in 2002. Peak Japanese sales of US$600 million were predicted for 2014 [319225]. In May 2000, Bayer predicted peak sales of Euro900 million [397137]. In July 2001, Lehman Brothers predicted a 75% chance that vardenafil would reach the market, and forecast peak sales of US $0.85 billion worldwide; the analyst also speculated that Bayer would seek a comarketing partner [414766].

Objectives: Chronic testicular pain (CTP) is defined as uni- or bilateral, intermittent or continuous testicular discomfort of at least 3 months duration that interferes with the patient's daily activities and prompts him to seek medical advice is a rather common urological manifestation of chronic pain syndrome. Diagnosis and treatment of CTP has been a difficult and often unrewarding clinical situation. Success rates of conservative and surgical measures including epididymectomy and orchiectomy rarely exceed 55-73% and 10-40%, respectively. We report our experience on microsurgical testicular denervation as therapeutic option in CTP., Patients and Methods: Following an extensive preoperative work-up (urine/semen cultures, transrectal ultrasound, testicular sonography, pain and orthopedic consultation) not revealing any pathologic abnormalities and a positive response to spermatic cord block, 35 patients underwent microsurgical testicular denervation. In brief, spermatic cord was dissected, vas deferens, cremasteric muscle and testicular vessels were separated. After identification of the testicular artery by application of vasodilatating agents using magnifying loops or the operating microscope, all structures besides the testicular artery, vas deferens and 1-2 lymphatic vessels were coagulated and transsected using bipolar diathermy., Results: After a mean follow-up of 31.5 months 34/35 (96%) patients are completely pain-free; no intra- or postoperative complications were encountered. No case of testicular atrophy or hydrocele formation was observed during postoperative follow-up., Conclusions: Microsurgical testicular denervation results in reliable and reproducible excellent therapeutic success rates of 96% and should be integrated in the management of CTP at an early stage. High success rates require adequate and meticulous diagnostic work-up of the patients by spermatic cord block using saline as placebo and different local anaesthetics as an initial therapeutic armentarium predicting postoperative outcome.

Objectives: Temporary genital numbness is a common side effect of long-distance cycling; cases of impotence have even been reported. Recent reports have shown that perineal compression leads to a decrease in penile blood flow. Reduced oxygen tension leads to penile fibrosis, which works counterproductively to the achievement of an erection. The shape of the bicycle saddle could be a factor affecting penile perfusion. The aim of this study is to find out the influence of different saddle designs on penile perfusion., Material and Methods: In 20 healthy athletic young men (mean age 26.8 years, range 21-31 years) without history of erectile dysfunction, transcutaneous oxygen pressure (PtcO2), which correlates with arterial and tissue PO2, was measured at the glans of the penis using a transcutaneous measurement device. All men were measured in a standing position before cycling, then during cycling in a seated position on a stationary bicycle. Four different bike saddle designs were used: (A) narrow heavily padded seat; (B) narrow seat with medium padding and a V-shaped groove in the saddle nose ("body geometry"); (C) wide unpadded leather seat; (D) women's special wide seat with medium padding and no saddle nose., Results: During cycling in all seats a decrease in penile oxygen pressure could be observed, reflecting perineal compression. But the differences were unexpected: seat (A) mean PtcO2 11.8 mmHg, decrease in initial oxygen pressure 82.4%; seat (B) mean PtcO2 20.8 mmHg, decrease in initial oxygen pressure 72.4%; seat (C) mean PtcO2 25.3 mmHg, decrease in initial oxygen pressure 63.6%; seat (D) mean PtcO2 62.3 mmHg, decrease in initial oxygen pressure 20.3%., Conclusions: Cycling in a seated position leads to a compression of perineal arteries with a consequent significant decrease in penile perfusion. But, there are unexpected differences between different saddle types. It was possible to demonstrate that the most important factor in safeguarding penile perfusion is not the amount of padding, but rather a saddle width which prevents sufficiently the compression of the perineal arteries.