Intermittent vs continuous docetaxel therapy in patients with metastatic castration-resistant prostate cancer - a phase III study (PRINCE).

OBJECTIVE: To investigate non-inferiority of intermittent docetaxel compared to continuous docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENT AND METHODS: The investigator initiated randomised phase III study included 187 chemotherapy-naïve patients with mCRPC who were allocated to two treatment arms: intermittent docetaxel and continuous docetaxel. Docetaxel was applied in both arms as weekly (35 mg/m2 ) or 3-weekly (75 mg/m2 ). The primary endpoint was 1-year survival, which was tested for non-inferiority (margin δ = 0.125). The secondary endpoints were: overall survival (OS), progression-free survival (PFS), median time to treatment failure (TTF), and toxicity. RESULTS: Of 156 eligible patients, 78 were allocated to each arm. The intermittent treatment met the non-inferiority criteria for 1-year survival (two-sided 95% confidence interval, -0.12, 18, P = 0.022), but not for OS, according to the result of a post hoc analysis. The differences between the study arms in PFS and TTF were not significant. The median (range) treatment holiday in the intermittent arm was 110 (13-486) days, or 38% of the overall treatment duration. Safety profiles of both study arms were comparable. The main limitation of this study was that the planned number of patients could not be recruited. CONCLUSION: Intermittent docetaxel chemotherapy was non-inferior to continuous therapy for 1-year survival; non-inferiority in regard to OS was not reached.

HAROW: the first comprehensive prospective observational study comparing treatment options in localized prostate cancer.

PURPOSE: To collect data on primary treatment decision and follow-up in patients with diagnosed, histologically confirmed localized (T1a-T2c/N0/M0) prostate cancer (PCa) for up to 5 years in a prospective observational non-interventional study. METHODS: Patients were non-randomly allocated to one of the five treatment strategies: hormone therapy, active surveillance, radiation, operation, or watchful waiting. RESULTS: A total of 3169 patients were included by 259 participating sites; 2957 patients had at least one follow-up visit. 54.8 % of tumors at baseline were staged as T1c, 38 % as T2a-T2c, and 7.1 % as T1a or T1b (missing: 0.2 %). 38.9, 32.6 and 26.6 % of patients were classified as low risk, intermediate risk, and high risk according to d'Amico, respectively (missing: 1.8 %). 56.6 % of patients underwent prostatectomy as primary therapy, 16.4 % received radiation, 6.9 % HT, 15.8 and 4.3 % decided for AS or WW. Mean follow-up was 28.4 months. Progression rates were between 8.6 % (RT) and 33.1 % (AS). CONCLUSION: Whereas RP remains the main treatment option of localized PCa, active surveillance appears to become an accepted and selectively employed treatment option. Careful selection of patients is documented by the highest proportion of patients with low risk (82.5 %), PSA density <0.2 ng/ml/ml (77.5 %), T1 staging (83.6 %), Gleason score ≤6 (92.5 %), ≤2 positive biopsies (79.4 %), and lowest mean PSA (5.8 ng/ml) in the AS group. The relatively high progression rate in the AS group has to be considered in the context of treatment changes; 71/155 patients had a documented change of treatment and 62 of them with a follow-up period of >3 months.

Interdisciplinary consensus statement on indication and application of a hydrogel spacer for prostate radiotherapy based on experience in more than 250 patients.

BACKGROUND: The aim of the study was to reach a consensus on indication and application of a hydrogel spacer based on multicentre experience and give new users important information to shorten the learning curve for this innovative technique. METHODS: The interdisciplinary meeting was attended by radiation oncologists and urologists, each with experience of 23 - 138 hydrogel injections (SpaceOAR®) in prostate cancer patients before dose-escalated radiotherapy. User experience was discussed and questions were defined to comprise practical information relevant for successful hydrogel injection and treatment. Answers to the defined key questions were generated. Hydrogel-associated side effects were collected to estimate the percentage, treatment and prognosis of potential risks. RESULTS: The main indication for hydrogel application was dose-escalated radiotherapy for histologically confirmed low or intermediate risk prostate cancer. It was not recommended in locally advanced prostate cancer. The injection or implantation was performed under transrectal ultrasound guidance via the transperineal approach after prior hydrodissection. The rate of injection-related G2-toxicity was 2% (n = 5) in a total of 258 hydrogel applications. The most frequent complication (n = 4) was rectal wall penetration, diagnosed at different intervals after hydrogel injection and treated conservatively. CONCLUSIONS: A consensus was reached on the application of a hydrogel spacer. Current experience demonstrated feasibility, which could promote initiation of this method in more centres to reduce radiation-related gastrointestinal toxicity of dose-escalated IGRT. However, a very low rate of a potential serious adverse event could not be excluded. Therefore, the application should carefully be discussed with the patient and be balanced against potential benefits.

Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05).

OBJECTIVE: To evaluate the efficacy and safety of gemcitabine and cisplatin in combination with sorafenib, a tyrosine-kinase inhibitor, compared with chemotherapy alone as first-line treatment in advanced urothelial cancer. PATIENTS AND METHODS: The study was a randomized phase II trial. Its primary aim was to show an improvement in progression-free survival (PFS) of 4.5 months by adding sorafenib to conventional chemotherapy. Secondary objectives were objective response rate (ORR), overall survival (OS) and toxicity. The patients included in the trial had histologically confirmed locally advanced and/or metastatic urothelial cancer of the bladder or upper urinary tract. Chemotherapy with gemcitabine (1250 mg/qm on days 1 and 8) and cisplatin (70 mg/qm on day 1) repeated every 21 days, was administered to all patients in a double-blind randomization of additional sorafenib (400 mg twice daily) vs placebo (two tablets twice daily) on days 3-21. Treatment continued until progression or unacceptable toxicity, the maximum number of cycles was limited to eight. The response assessment was repeated after every two cycles. RESULTS: Between October 2006 and October 2010, 98 of 132 planned patients were recruited. Nine patients were ineligible. The final analysis included 40 patients in the sorafenib and 49 patients in the placebo arm. There were no significant differences between the two arms concerning ORR (sorafenib: complete response [CR] 12.5%, partial response [PR] 40%; placebo: CR 12%, PR 35%), median PFS (sorafenib: 6.3 months, placebo: 6.1 months) or OS (sorafenib: 11.3 months, placebo: 10.6 months). Toxicity was moderately higher in the sorafenib arm. Diarrrhoea occurred significantly more often in the sorafenib arm and hand-foot syndrome occurred only in the sorafenib arm. The study was closed prematurely because of slow recruitment. CONCLUSION: Although the addition of sorafenib to standard chemotherapy showed acceptable toxicity, the trial failed to show a 4.5 months improvement in PFS.

[Urinary incontinence after radical prostatectomy for prostate cancer-data from 17,149 patients from 125 certified centers]. / Harninkontinenz nach radikaler Prostatektomie beim Prostatakarzinom ­ aktuelle Daten von 17.149 Patienten aus 125 zertifizierten Zentren.

BACKGROUND: In addition to erectile dysfunction, urinary incontinence is the most common functional limitation after radical prostatectomy (RPE) for prostate cancer (PCa). The German S3 guideline recommends informing patients about possible effects of the therapy options, including incontinence. However, only little data on continence from routine care in German-speaking countries after RPE are currently available, which makes it difficult to inform patients. OBJECTIVE: The aim of this work is to present data on the frequency and severity of urinary incontinence after RPE from routine care. MATERIALS AND METHODS: Information from the PCO (Prostate Cancer Outcomes) study is used, which was collected between 2016 and 2022 in 125 German Cancer Society (DKG)-certified prostate cancer centers in 17,149 patients using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26). Changes in the "incontinence" score before (T0) and 12 months after RPE (T1) and the proportion of patients who used pads, stratified by age and risk group, are reported. RESULTS: The average score for urinary incontinence (value range: 0-worst possible to 100-best possible) was 93 points at T0 and 73 points 12 months later. At T0, 97% of the patients did not use a pad, compared to 56% at T1. 43% of the patients who did not use a pad before surgery used at least one pad a day 12 months later, while 13% use two or more. The proportion of patients using pads differs by age and risk classification. CONCLUSION: The results provide a comprehensive insight into functional outcome 12 months after RPE and can be taken into account when informing patients.

Laparoscopic adrenalectomy in urological centres - the experience of the German Laparoscopic Working Group.

OBJECTIVE: To evaluate the safety and feasibility of laparoscopic adrenalectomy (LA) performed in several German centres with different laparoscopic experience, as LA has become the gold-standard approach for benign surgical adrenal disorders; however, for solitary metastasis or primary adrenal cancer its precise role is uncertain. PATIENTS AND METHODS: The data of 363 patients who underwent a LA were prospectively collected in 23 centres. All centres were stratified into three groups according to their experience: group A (<10 LAs/year), group B (10-20 LAs/year) and group C (>20 LAs/year). In all, 15 centres used a transperitoneal approach, four a retroperitoneal approach and four both approaches. Demographic data, perioperative and postoperative variables, including operating time, surgical approach, tumour size, estimated blood loss, complications, hospital stay and histological tumour staging, were collected and analysed. RESULTS: The transperitoneal approach was used in 281 cases (77.4%) and the retroperitoneal approach was used in 82 patients (22.6%). In all, 263 of 363 lesions (72.5%) were benign and 100 (27.5%) were malignant. The mean (sd) operating time was 127.22 (55.56) min and 130.16 (49.88) min after transperitoneal and retroperitoneal LA, respectively. The mean complication rates for transperitoneal and retroperitoneal LA were 5% and 10.9%, respectively. CONCLUSION: LAs performed by urologists experienced in laparoscopy is safe for the removal of benign and malignant adrenal masses. LA for malignant adrenal tumours should be performed only in high-volume centres by a surgeon performing at least >10 LAs/year.

A Randomized Phase IIa Trial with Temsirolimus versus Sunitinib in Advanced Non-Clear Cell Renal Cell Carcinoma: An Intergroup Study of the CESAR Central European Society for Anticancer Drug Research-EWIV and the Interdisciplinary Working Group on Renal Cell Cancer (IAGN) of the German Cancer Society.

BACKGROUND: Non-clear cell renal cell cancers (nccRCC) are rare entities, and the optimal therapy in metastatic disease has still to be defined. METHODS: In this small prospectively randomized phase IIa multicenter trial, we investigated temsirolimus (TEM) versus sunitinib (SUN) as first-line therapy in patients with metastatic nccRCC. The patients were randomized 1:1 to either TEM in a dose of 25 mg i.v. once a week or SUN with 50 mg p.o. daily for 4 weeks on and 2 weeks off. Primary endpoint was progression-free survival (PFS). In total, 22 patients were included with predominantly papillary RCC (16/22) followed by chromophobe RCC and others. RESULTS: The male to female ratio was 16:6. The tumor control rate (CR + PR + SD) was 58% for TEM and 90% for SUN-treated patients. There was also a trend for improved PFS with 9.3 versus 13.2 months (HR 1.64; 95% CI 0.65-4.18) in favor of SUN. There was no trend for overall survival. CONCLUSIONS: Despite this trial had to be terminated earlier due to low recruitment, the results match the other studies published so far with the mTOR inhibitor everolimus and SUN, which show a trend in favor of SUN for ORR and PFS.

Impact of clinical variables on predicting disease-free survival of patients with surgically resected renal cell carcinoma.

OBJECTIVE: To determine the value of particular clinical variables for the preoperative prognostic Cindolo formula (PPCF) to predict disease-free survival (DFS) of patients with surgically treated renal cell carcinoma (RCC). PATIENTS AND METHODS: In all, 771 consecutive patients (T1-4NxM0) who had radical or partial nephrectomy were reviewed retrospectively. For each patient with RCC, PPCF was constructed according to clinical size and clinical presentation. On the basis of PPCF, patients were divided into Cindolo good prognosis (CGP) and Cindolo poor prognosis (CPP) groups. We also analysed further clinical variables (Eastern Cooperative Oncology Group score, American Society of Anesthesiologists score, body mass index, hepatic dysfunction, night sweat, fever, value of blood platelets, leukocytes, haemoglobin level, gender, age and location). DFS was estimated using the Kaplan-Meier method. Univariable and multivariable Cox proportional hazard regression models were fitted to determine associations between the PPCF, measured clinical features, and DFS. RESULTS: Four of the variables emerged as statistically significant for DFS from the univariable analysis (P < 0.001), i.e. clinical presentation, clinical tumour size, haemoglobin level and blood platelet count. In the multivariable analysis, only clinical tumour size and blood platelet count remained significant for DFS. By contrast, clinical presentation, used in the PPCF, had no significant influence. According to the PPCF we developed the preoperative Amissah Prognosis Score (PAPS) calculated as (0.19 x clinical size) + (0.492 x platelet count (400/nL = 1) with a threshold between the two resulting prognosis groups at 1.76. The multivariable hazard ratio (95% confidence interval, CI) for the PAPS was 2.98 (2.15-4.12) (P < 0.001) compared to a hazard ratio for the PPCF of 1.36 (0.99-1.87) (P = 0.061). Furthermore, the predictive ability was greater when using the PAPS (area under the curve 0.721; 95% CI, 0.680-0.763; P

Whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH) and healthy male inhabitants (HMI) and prostatic tissue selenium levels (PTSL) in patients with PC and BPH.

BACKGROUND: The aim of this exploratory study was to evaluate whether significant differences exist between whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH), healthy male inhabitants (HMI) in northern Bavaria and the normal value. Furthermore, we investigated whether differences exist between prostatic tissue selenium levels (PTSL) in patients with PC, BPH and the benign tissue surrounding the PC. MATERIAL AND METHODS: We prospectively evaluated WBSL in 24 patients with PC, 21 patients with BPH, and 21 HMI. Measurements of PTSL were performed in 17 patients with PC and 22 patients with BPH. In 9 cases with PC, measurements were also done in the benign tissue surrounding the carcinoma. Measurements were performed using automated graphite furnace atomic absorption spectrophotometry. RESULTS: In patients with PC, there is a significantly lower WBSL in comparison to HMI (p=0.04). There is no significant difference in WBSL between BPH-patients and HMI (p=0.13) and between PC- and BPH-patients (p=0.67). In all patients and the HMI, there is a significantly lower WBSL in comparison to the recommended normal value of 85-162 microg/l (p<0.01). There is no significant difference in PTSL between PC and BPH (p=0.49), and between PC and the tissue compartment surrounding the PC (p=0.56). PTSL seemed to be reduced in the compartment surrounding the PC in comparison to BPH (p=0.03). In PC-patients, there is no significant correlation between WBSL and prostate specific antigen (PSA) (? = -0.20; p=0.36), Gleason score (? = 0.32, p=0.13), and T-stage (? = 0.22; p=0.23). CONCLUSION: Since the WBSL measured in all men with PC and BPH, and in HMI participating in our study were significantly lower than the recommended normal range, our findings may support the recommendation of selenium supplementation.

Long-term treatment of erectile dysfunction with a phosphodiesterase-5 inhibitor and dose optimization based on nocturnal penile tumescence.

OBJECTIVE: To test the hypothesis that a variable dosage of the oral phosphodiesterase type 5 (PDE5) inhibitor sildenafil (25, 50, 100 mg) or vardenafil (5, 10, 25 mg) determined according to results obtained from nocturnal penile tumescence and rigidity (NPTR, RigiScan), given nightly for 1 year, can improve spontaneous erectile function (EF) in men with mild-to-moderate arteriogenic erectile dysfunction (ED); this regimen was compared with a fixed daily dosage of sildenafil 25 mg or vardenafil 5 mg. PATIENTS AND METHODS: In a prospective open-label, parallel-group trial 154 men with ED were randomized either to fixed low-dose sildenafil 25 mg or vardenafil 5 mg (group 1) or to the lowest erectile dosage of sildenafil (25, 50 or 100 mg) or vardenafil (5, 10 or 20 mg) (group 2) provoking an erectile event as measured by NPTR nightly for 1 year. The EF domain of the International Index of Erectile Function (IIEF) was assessed before and 1 year after the beginning of treatment, and at 4 weeks after ending treatment. RESULTS: After 1 year, 27 of 63 (64%) evaluable men in group 1 had an EF domain score in the normal range, vs 46 of 61 (75%) men in group 2. After the subsequent 4-week wash-out phase, both groups continued to have improved EF domain scores; 22 of 63 (35%) men in group 1 still had a score in the normal range, whereas 38 of 61 (62%) in group 2 had a normal score. The EF domain score in group 1 and 2 improved significantly after 1 year of treatment, from 13.6 to 18.9, and 15.1 to 23.9, respectively (P < 0.01). After the subsequent 4-week wash-out phase, men from both groups maintained this significant level of EF, at 17.1 and 22.4, respectively (P < 0.05). CONCLUSION: Nightly PDE5-inhibitor treatment 1 year in a dosage determined by NPTR measurements results in better EF than giving a fixed dosage of sildenafil (25 mg) or vardenafil (5 mg). This improvement persisted for >4 weeks beyond the end of treatment. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.

Improved spontaneous erectile function in men with mild-to-moderate arteriogenic erectile dysfunction treated with a nightly dose of sildenafil for one year: a randomized trial.

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.

Evaluation of tetrahydrobiopterin (BH4) as a potential therapeutic agent to treat erectile dysfunction.

AIM: Nitric oxide (NO)-mediated smooth muscle relaxation causes penile erections. The endothelial NO synthase (eNOS) coenzyme tetrahydrobiopterin (BH4) converts eNOS-mediated catalytic activity from oxygen radical to NO production, improving endothelial function and vascular smooth muscle relaxation. METHODS: Using quantitative immunohistochemistry, 8-isoprostane and nitrotyrosine concentrations were compared in cavernosal tissue from 17 potent and 7 impotent men, and the effect of single oral doses of BH4 on penile rigidity and tumescence was investigated. The pharmacodynamic effect of single oral doses of BH4 on penile rigidity and tumescence was investigated in a randomized, placebo-controlled, double-blind cross-over fashion in 18 patients with erectile dysfunction (ED) while receiving visual sexual stimulation. RESULTS: 8-Isoprostane content in endothelium and smooth muscle was significantly higher in impotent patient samples; the level of nitrotyrosine was unchanged in ED patients. Relative to placebo, a single dose of 200 mg BH4 led to a mean increase in duration of > 60% penile rigidity (33.5 min [95% confidence interval (CI): 13.1-49.3] at base and 29.4 min [95% CI: 8.9-42.2] at tip). A 500-mg dose increased the relative duration of > 60% penile rigidity by 36.1 min (95% CI: 16.3-51.8) at the base and 33.7 min (95% CI: 11.4-43.9) at the tip. Treatments were well tolerated. CONCLUSION: BH4 treatment is suggested to switch eNOS catalytic activity from super-oxide to NO formation, leading to a reduced formation of free radical reaction product 8-isoprostane without alteration of nitrotyrosine. The observed results make BH4 a suitable candidate as an ED treatment through reconstitution of altered catalytic activity of the eNOS.

Patients with localised prostate cancer (t1 - t2) show improved overall long-term survival compared to the normal population.

BACKGROUND: Little information is available on the long-term outcomes of patients with localised prostate cancer. OBJECTIVE: To examine the long-term survival of patients with localised prostate gland carcinoma T1 - T2, N0, M0 (UICC stage I and II) compared to the normal population. DESIGN: Retrospective cohort. SETTING: Regensburg, Germany. PARTICIPANTS: Data on 2121 patients with histologically-confirmed, localised prostate cancer diagnosed between 1998 and 2007 were extracted from the cancer registry of the tumour centre in Regensburg, Germany. MEASUREMENTS: Overall survival rate in the patient cohort was estimated and compared to the expected survival rate of a comparable group in the general population derived from the official life-tables of Germany stratified by age, sex and calendar year. RESULTS: Ten years after diagnosis, patients with stage I and II localised prostate gland carcinoma had an approximately 10% increase in survival compared to the normal male population (Relative Survival = 110.7%, 95%-CI 106.6 - 114.8%). LIMITATIONS: We did not examine the effect of cancer treatment or cancer aggressiveness on the overall survival of patients. We did not assess the incidence of subsequent non-primary cancers in our patient population or how this incidence affects the patients' follow-up care and survival. CONCLUSIONS: Patients with stage I+II localised prostate gland carcinoma have improved survival compared with the normal male population. This finding cannot be explained solely by the administration of prostate carcinoma treatments, suggesting that men who participate in PSA screening may have better overall health behaviors and care than men who do not participate in screening. Future research should examine how treatment choice, especially an "active surveillance" approach to care, affects survival in these patients more than ten years after diagnosis.

Patients responding to phosphodiesterase type 5 inhibitor therapy: what do their sexual partners know?

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors are an efficacious therapy in men with erectile dysfunction (ED). There are only a few studies that also focus on the participating couples during PDE5 inhibitor therapy. AIM: To determine to what extent patients personally informed their sexual partners about their ongoing PDE5 inhibitor therapy. MAIN OUTCOME MEASURES: Likelihood of informing the female partner by the patient himself about the use of PDE5 inhibitors. METHODS: A total of 216 men (mean age 62.3 years) with ED were successfully treated with PDE5 inhibitors in three independent centers. After an interval of at least 3 months of successful ED therapy, all patients were asked by questionnaire whether their sexual partners were informed of their PDE5 inhibitor therapy. RESULTS: Eighty-two percent of the patients were exclusively involved in one stable sexual relationship, 9.7% of the men admitted to having changing sexual partners, and 6% did not give any information at all about their sexual partners. Twenty percent of the men had a severe ED (International Index of Erectile Function [IIEF-5] <11). Forty-nine percent showed a moderate ED (IIEF-5 11-16) and 31% suffered a mild ED (IIEF-5 >16). PDE5 inhibitor medication was used 1.2 times/month by men with a severe ED, 2.1 times/month by patients with a moderate ED, and 2.9 times/month by men with a mild ED. Forty-one (93%) of the 44 patients with a severe ED informed their sexual partners that they were taking PDE5 inhibitors. In the patient group with moderate ED, 49 (47%) of 105 patients and only 14 (21%) of 67 of the patients with mild ED shared this information with their partners. CONCLUSION: Less than 40% of the patients suffering a moderate or mild ED using PDE5 inhibitors shared this information with their partners. It seems that patients find ED so disturbing that many patients do not inform their partners of PDE5 inhibitor use.

The economic costs of overactive bladder in Germany.

OBJECTIVE: To estimate the annual direct costs of overactive bladder (OAB) in Germany from a societal perspective. METHODS: Direct costs were calculated based on prevalence figures and medical resource utilisation due to hospitalisation, office-based physician visits, visits to other health care professionals, medication, medical aids and devices, and nursing care. RESULTS: A total of 6.48 million adults>or=40 yr of age in Germany are affected by OAB, and 2.18 million of these individuals experience incontinence. The annual incidence of comorbidities attributable to OAB is 310,000 for skin infections, 40,000 for falls, 12,000 for fractures, and 26,000 for depression (based on 2004 census data). Direct OAB-related costs per year are euro3.98 billion, with euro1.76 billion covered by statutory health insurance, euro1.80 billion by nursing care insurance, and euro0.41 billion by the patients. Nursing care accounts for euro1.80 billion of total costs (45%), devices account for euro0.68 billion (17%), physician visits account for euro0.65 billion (16%), complications account for euro0.75 billion (19%), and medication accounts for euro0.08 billion (2%). CONCLUSION: OAB imposes a substantial economic burden on German health and nursing care, insurance, and on patients with OAB. Direct annual costs are comparable to those of other chronic diseases such as dementia or diabetes mellitus.

Merkel cell carcinoma -- a rarity in the urogenital tract.

BACKGROUND: Merkel cell carcinoma -- a rare, aggressive cancer of the skin integument - is being increasingly diagnosed but represents an absolute rarity in the urogenital tract. CASE REPORT: We report on a 70-year-old man who was referred to us with suspected testicular cancer. The pathology report revealed a metastasized Merkel cell carcinoma. Fulminant disease progression under chemo-therapy (regimen as for small cell lung cancer) resulted in death 5 months later. CONCLUSION: The patient described is considered to be the first to develop testicular metastasis derived from Merkel cell carcinoma. Besides neuroendocrine and epithelial antigen tests, somatostatin receptor scintigraphy is a helpful diagnostic tool. New receptor-associated therapies may allow more effective and less toxic treatment modalities in the mostly elderly or immune deficient patients.

Differential endostatin binding to bladder, prostate and kidney tumour vessels.

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.

Vessels in benign prostatic hyperplasia contain more binding sites for endostatin than vessels in normal prostate tissue.

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.