Prevention strategies for prostate cancer.

Through the last decade consideration of the role of vitamins and minerals in primary prevention of genitourinary tumors has dramatically changed. Despite all efforts efficacy of a specific compound has not been proven, so far. In consequence, recommendations for a use of vitamins or other supplements with the intention of prostate cancer prevention should be avoided today. In contrast, there is some evidence that life style modification might be helpful: recent investigations suggest that smoking may be involved in prostate cancer carcinogenesis. In addition, there is evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet might not only prevent prostate cancer but also harbors additional beneficial effects on general health. This move from single compounds to more complex diets can be considered as a change of paradigm in prostate cancer prevention and could be the starting point of future epidemiological research. Disappointing findings with regards to nutritional cancer prevention contrast with a solid evidence concerning the efficacy of chemoprevention using 5a-reductase inhibitors: Long-term use of Finasteride and Dutasteride significantly reduces prostate cancer detection. Further candidate drugs are under investigation. However, translation of these findings into urological practice remains a matter of controversial discussion.

[Urinary bladder cancer as a late sequela of spinal cord injury : Decision-making aids for assessment of this causal association]. / Harnblasenkarzinom als Spätfolge einer Querschnittlähmung : Entscheidungshilfe für eine Zusammenhangsbegutachtung.

BACKGROUND: There is to date no convincing literature that has assessed the association between traumatic spinal cord injury (SCI) and the later development of urinary bladder cancer. The aim of this work is to present medical experts as well as the national accident insurance and the social courts decision-making aids based on the latest medical scientific knowledge, for assessment of this causal association. MATERIALS AND METHODS: A study conducted between April 1998 and March 2017 in the BG Trauma Hospital Hamburg forms the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 32 out of 6432 treated outpatient and inpatient SCI patients. Furthermore, relevant published literature was taken into consideration for the decision-making aids. RESULTS: It was found that urinary bladder cancer in SCI patients occurs at a considerably younger age as compared to the general population, more frequently shows muscle invasive carcinoma with a higher grade at first diagnosis and a higher proportion of the more aggressive squamous cell carcinoma than that of the general population. Correspondingly, the survival time is extremely unfavorable. For medical experts a matrix was compiled where the various influencing factors, either for or against the recognition of an association between SCI and urinary bladder cancer, were weighted according to their relevance. CONCLUSION: The results showed that urinary bladder cancer in SCI patients differs considerably from that of able-bodied patients. These differences drastically shorten the survival time. A study on patients with spina bifida, i.e., a congenital spinal cord disorder, corroborates these observations. They indicate histopathological differences that have so far been intangible.

Safety and efficacy of vardenafil versus sertraline in the treatment of premature ejaculation: a randomised, prospective and crossover study.

We investigated safety and efficacy of vardenafil and sertraline in premature ejaculation (PE). Seventy-two men graded their primary PE on a scale of 0-8 (0 = almost never, 8 = almost always). Intravaginal ejaculatory latency time (IELT) was measured. Patients were included if they scored their PE as 4 or greater and their IELTs were less than 1.30 min. After 6 weeks of behavioural psychosexual therapy, 49 patients still had a PE of 4 or greater and an IELT less than 1.30 min and they were randomised: 6 weeks vardenafil (10 mg) or sertraline (50 mg). After a wash-out phase for 1 week, medication was changed in a cross-over design. Initially, all 72 men with PE received behavioural therapy. Twenty-three men were satisfied with treatment and excluded. The remaining 49 men graded their PE as 5.94 +/- 1.6 and IELT was 0.59 min and patients were randomised. Four men discontinued the study. Vardenafil improved PE grading: 2.7 +/- 2.1 (P < 0.01) and IELT increased to 5.01 +/- 3.69 (P < 0.001). PE grading improved 1.92 +/- 1.32, (P < 0.01) and IELT 3.12 +/- 1.89 (P < 0.001) with sertraline. It is concluded that vardenafil and sertraline are useful agents in the pharmacological treatment of PE.

[Qualitative and quantitative analysis of urolithiasis with the Rietveld method (x-ray diffraction)]. / Genaue qualitative und quantitative Harnsteinanalyse mit Hilfe der Rietveld-Methode (Röntgendiffraktion).

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

[Is rehabilitation of erectile function following pelvic surgery reasonable? Review of the literature: from sports to PDE5 inhibitors]. / Ist eine Rehabilitation der erektilen Funktion nach beckenchirurgischen Eingriffen sinnvoll? Literaturübersicht vom Sport bis zur PDE-5-Inhibitoren-Gabe.

Increasingly, urologists are seeing patients with erectile dysfunction after pelvic operations. In most cases, radical prostatectomy is the cause. Even when a nerve-sparing procedure is performed, approximately 50% of the patients suffer from erectile dysfunction. This report discusses the causes and theoretical therapies, including lifestyle changes, strategies for neuroregeneration and the associated prevention of apoptosis of the smooth muscle of the corpus cavernosum and improvement of the corpora cavernosa by increased oxygenation. According to the international literature, many of these agents and lifestyle modifications display promise for treating impotence. Early treatment for patients recovering from pelvic operations seems to be reasonable. It is assumed that the natural recovery of erections may take as long as 18 to 24 months postsurgery or even longer; however, treatment modalities may reduce the time to erectile recovery.

[Results of the evaluation of 85,337 urinary stone analyses]. / Ergebnisse der Harnsteinanalyse von uber 85337 Harnsteinen.

In this work 85337 urinary stones were analysed by X-ray diffraction in regard of their qualitative and quantitative composition. Urological practitioners and hospitals from all areas of the former FRG sent urinary stones to the Institute of Mineralogy in Bonn and to the Urology Department of the St Josef-Hospital in Troisdorf up to December 31st, 1994. The evaluations were carried out with special regard to the frequency of occurrence and to the quantity portions. The frequency of occurrence of one component describes the percentage of the urinary stones which contain this component. The quantity portion describes the average amount of one component in regard to all urinary stones which contain this component as well. The frequency of occurrence of whewellite was 75.77% and of wheddellite 46.41%. 34.25% of all calculi were monomineralic and 55.3% were bimineralic.

[Testicular perfusion injury. Cytokines and cell adhesion molecules in humans]. / Testikuläre Ischämie. Verlauf von Zytokinen und Zelladhäsionsmolekülen beim Menschen.

BACKGROUND: Ischemia and reperfusion (I/R) lead to cellular damage. A disturbance of testicular perfusion occurs during the therapy of cryptorchidism and in cases of testicular torsion. This results in the activation of mediator cells with an increasing synthesis of mediators of infection like TNF-alpha and the expression of cell adhesion molecules like ICAM (intercellular adhesion molecule) and VCAM (vascular cell adhesion molecule) at the cellular surface. METHODS: The expression of the cytokines IL-10 and TNF-alpha and the adhesion molecules ICAM and VCAM after defined testicular I/R injury in nine male transsexuals was evaluated with rt-PCR. Furthermore we examined lactate and the diameter of the testicular tubulus under ischemic conditions. RESULTS: During ischemia ICAM, IL-10, and VCAM do not show significant changes on the side of testicular ischemia and the contralateral side; the same was seen for the tubulus diameter. TNF-alpha and the testicular lactate values showed a significant change of the expression pattern. DISCUSSION: The statistical changes of TNF-alpha and testicular lactate are the expression of leukocyte migration, infectious reaction, and immune response. To what extent the TNF-alpha expression represents a severe immunological reaction remains undefined. This human study shows primary results for the immunological understanding of and cellular response to testicular ischemia.

[Chemoprevention of prostate cancer. Current status]. / Chemoprävention des Prostatakarzinoms. Stand der Dinge.

Fueled by the results from recently published large interventional trials the topic of chemoprevention of prostate cancer has increasingly attracted the interest of practicing urologists. In this analysis the term"chemoprevention" comprises all agents not included in regular food intake. If possible, the results from interventional studies were considered. Today, it must be accepted as evidence-based that chemoprevention of prostate cancer by 5alpha-reductase inhibition using finasteride is possible. Furthermore, there is increasing evidence that selective estrogen receptor modulators (SERMs) may also have preventive potential. Prospective interventional trials investigating these substances are currently underway. Considering the high incidence and the fact that the diagnosis of prostate cancer has serious impact on the future life of the respective individuals further scientific evaluation of chemoprevention of prostate cancer is mandatory.

[Does cigarette smoking influence the survival of patients with prostate cancer?]. / Beeinflusst Rauchen das Uberleben von Prostatakarzinompatienten?

In the last few years, prostate cancer has become one of the most common causes of mortality worldwide. It is therefore important to detect possible risk factors for this malignant disease. Besides risk factors which increase incidence, attention should be paid to factors which have a possible influence on the course of the disease. In our analysis, we demonstrate a worse course for the disease in patients with prostate cancer who smoked cigarettes at the time of first diagnosis. In spite of comparable staging, grading and PSA values at the time of primary diagnosis, individuals who smoked had a threefold higher risk of dying from prostate cancer. This effect is probably caused by metabolic changes which are activated by cigarette smoking and promote tumor growth and the development of metastases.

[Prevention of osteoporosis--important for the urologist?]. / Prävention der Osteoporose--wichtig für den Urologen?

Osteoporosis is a systemic disease of the bones with increasing incidence in the elderly. Over the age of 50 years bone mineral density continuously decreases resulting in osteoporotic fracture. Osteoporosis is positively correlated with late-onset hypogonadism and increases under androgen deprivation therapy. The evaluation of osteoporosis should be done in cooperation with an endocrinologist. Measurement of bone mineral density is recommended before starting androgen deprivation therapy. Patients with fracture and/or decreased bone mineral density 2.5 or more standard deviations below normal peak bone mass of young men should be treated. The appropriate treatment is calcium and vitamin D substitution combined with oral or i.v. administration of bisphosphonates.

[The Prostate Cancer Prevention Trial (PCPT). Relevance for clinical practice]. / Das "Prostate Cancer Prevention Trial" (PCPT). Die Bedeutung für den klinischen Alltag.

The Prostate Cancer Prevention Trial (PCPT) has been the first interventional trial directly aimed at the prevention of prostate cancer. A total of 18,882 men over 55 years with a PSA serum level less than 3.0 ng/ml were randomized to receive either the 5-alpha-reductase inhibitor finasteride 5 mg/day or placebo for 7 years. Despite a 25% reduction of prostate cancers in the treatment arm the results were discussed controversially. This criticism was mainly due to the observation of significantly more high-grade cancers in the finasteride group. Meanwhile, results of extensive follow-up analyses have been published suggesting that this finding is most likely due to optimized tumor detection in smaller glands. Further work-up demonstrated that PSA diagnosis and the histopathological examination were not compromised by finasteride. Furthermore, in addition to a decrease of prostate cancer the amount of prostatic intraepithelial dysplasia (PIN) was also reduced under finasteride. Future research must now aim at defining high-risk groups specifically profiting from chemoprevention with a 5-alpha-reductase inhibitor.

[Immunotherapy of metastatic renal cell carcinoma with interleukin-2, interferon-alpha2a and erythropoietin-beta]. / Immuntherapie des metastasierten Nierenzellkarzinoms mit Interleukin-2, Interferon-alpha2a und Erythropoetin-beta.

BACKGROUND: The combination of interferon-alpha2a (IFN-alpha2a) and interleukin-2 (IL-2) induces objective responses in patients with metastatic renal cell carcinoma (MRCC). Anaemia is associated with poor cancer control and reduced quality of life. The aim of the study was to investigate response rate and quality of life in patients with MRCC receiving the combination of Erythropoetin, IFN-alpha2a and IL-2. MATERIAL AND METHOD: Patients with MRCC received epoetin beta (150 IU/kg and haemoglobin <130 g/l or 75 IU/kg and haemoglobin >or=130 g/l) three times weekly, from 14 days before and continuing throughout immunotherapy. In weeks 3-6 the patients received IFN-alpha2a 6 x 10(6) IU/m2 and IL-2 4.5 x 10(6) IU/m2 three times weekly on days 1, 3 and 5. The treatment was repeated two times and in the case of success a third cycle was added. The quality of life was assessed with the FACT questionnaire for fatigue, before, during and after therapy. RESULTS: A total of 21 patients were treated, 19 of whom could be evaluated concerning response, toxicity and quality of life. We observed 1 complete remission, 2 partial remissions, 5 cases of stable disease and 11 with progressive disease. The overall response rate was 16%. Toxicity was mild to moderate; there were no WHO grade III or IV toxicity. The quality of life increased in ten patients, nine of whom exhibited an increase in their haemoglobin during therapy. Five of the nine patients with decreased quality of life also experienced a decrease in their haemoglobin. The correlation of increased haemoglobin and quality of life was significant (p<0.05). CONCLUSION: The combination of IFN-alpha2a, IL-2 and epoetin beta resulted in objective remissions with mild to moderate toxicity. The quality of life correlates significantly with increasing haemoglobin.

[Nutrition, lifestyle, physical activity, and supportive care during chemotherapeutic treatment]. / Ernährung, Lebensweise, Aktivitäten und supportive Massnahmen unter chemotherapeutischer Behandlung.

With improvements in cancer survival rates, more patients with cancer are living longer and the influence of nutrition, lifestyle, physical activity as well as supportive care during and after chemotherapy is of increasing interest. In several malignancies smoking cessation increases cancer survival. Similar effects are expected by healthy nutrition. Regular physical activity of cancer patients reduces drug interactions of chemotherapy, decreases the number of comorbid conditions, and helps patients maintain independence as long as possible. For supportive care during chemotherapy the 5-HT3 receptor antagonists are more effective for the prevention of chemotherapy-induced nausea and vomiting. There are several colony-stimulating factors (e.g. GCSF, erythropoietin) for hematopoietic recovery post-chemotherapy. Altogether supportive care of chemotherapy reduces toxicity and increases efficacy.

[Use of lubricants in urology. Indications and results]. / Der Einsatz von Gleitmitteln in der Urologie. Indikationen und Ergebnisse.

Lubricants are used for catheterization and/or endoscopic maneuvers. "The lubricant" should guarantee sufficient lubrification of the urinary tract, good visualization during endoscopy, and excellent local anesthesia. Additionally, asepsis or reliable control of the local bacterial flora of the urethra should be ensured. Modern lubricants fulfil these recommendations; in addition, they provide therapeutic opportunities for local therapy, for instance, of non-gonococcal urethritis. The latest results show that there are a few lubricants with antimicrobiotic influence on MRSA (methicillin-resistant Staphylococcus aureus), which is of great importance because of the steady increase in MRSA-dependent infections.

[Use of free dermal grafts in urology]. / Nutzung freier Hauttransplantate in der Urologie.

Plastic reconstructive surgery is of increasing importance in urology. The choice of the optimal material, for example dermal graft or musculocutaneous graft, is decisive for the operative success of each procedure. We present the technique, indications, innovations, and mutual fields with other operative disciplines.

[Superficial bladder cancer: Transurethral resection and instillation therapy]. / Oberflächliches Harnblasenkarzinom : Transurethrale Blasentumorchirurgie und Instillationstherapie.

Bladder cancer is the fifth most common tumor in men with the incidence of bladder tumors continuing to rise in industrialized and developed countries. Because 80% of all bladder tumors grow on the surface, endoscopic transurethral resection (TUR-B) can be used for complete removal. Due to continuous technical developments and improvements of endoscopic equipment, video imaging and bipolar resection (TUR-IS) offers a high level of safety. Despite optimal equipment, intra- and postoperative complications in transurethral electrosurgery of bladder tumors may occur.

The Whitaker test, a useful tool in renal grafts?

OBJECTIVES: To evaluate the Whitaker test, a pressure flow examination, for its prognostic value in dilated renal transplants because urologic complications, such as ureteral stenosis, are significant problems after kidney transplantation. METHODS: Twenty-five patients with obstruction of the renal transplant and subsequent percutaneous nephrostomy were evaluated with a urodynamic pressure flow test (Whitaker test) in combination with antegrade pyeloureterography. The results of the Whitaker test were related to the serum creatinine values. RESULTS: The Whitaker test demonstrated normal pressure flow (less than 15 cm H(2)O) in 7 patients, pressure flow between 15 and 25 cm H(2)O in 10, and pathologic results (greater than 25 cm H(2)O) in 8 patients. After percutaneous nephrostomy, the serum creatinine level decreased in 22 of 25 patients, although the urodynamic pressure flow revealed a significant obstruction (Whitaker test greater than 25 cm H(2)O) in only 8 patients. The sensitivity of the Whitaker test to indicate the relevance of post-renal transplant stenosis in comparison to the declining serum creatinine level after successful percutaneous nephrostomy was 79%; the specificity was 50%. CONCLUSIONS: The results of our study indicate that a decreasing creatinine level in correlation with radiologic results is the leading finding in dilation of transplanted kidneys without rejection. The Whitaker test, as a pressure flow examination, provided no additional information.

Phase II trial of titanocene dichloride in advanced renal-cell carcinoma.

Titanocene dichloride was capable of inhibiting the growth of different types of human tumors in vitro. A total of 14 patients with metastatic renal-cell carcinoma (RCC) received 270 mg/m2 titanocene dichloride every 3 weeks for 6 weeks. Although the toxicities and side effects encountered were mild to moderate, no partial or complete response was detectable. In conclusion, titanocene dichloride has no advantage in the therapy of RCC.

Histamine H3A receptor-mediated inhibition of noradrenaline release in the mouse brain cortex.

Mouse brain cortex slices preincubated with 3H-noradrenaline were superfused with physiological salt solution containing desipramine plus a drug with alpha 2-adrenoceptor antagonist properties, and the effects of histamine receptor ligands on the electrically (0.3 Hz) evoked tritium overflow were studied. The evoked overflow (from slices superfused with phentolamine) was inhibited by histamine (pIC35 6.53), the H3 receptor agonist R-(-)-alpha-methylhistamine (7.47) and its S-(+)-enantiomer (5.82) but not influenced by the H1 receptor agonist 2-(2-thiazolyl)-ethylamine 3.2 mumol/l and the H2 receptor agonist dimaprit 10 mumol/l. The inhibitory effect of histamine was not affected by the H1 receptor antagonist dimetindene 1 mumol/l and the H2 receptor antagonist ranitidine 10 mumol/l. The concentration-response curve of histamine (determined in the presence of rauwolscine) was shifted to the right by the H3 receptor antagonists thioperamide (apparent pA2 8.67), impromidine (7.30) and burimamide (6.82) as well as by dimaprit (6.16). The pA2 values of the four drugs were compared with their affinities for H3A and H3B binding sites in rat brain membranes (West et al. 1990 Mol Pharmacol 38:610); a significant correlation was obtained for the H3A, but not for the H3B sites. The results suggest that noradrenaline release in the mouse brain cortex is inhibited by histamine via H3A receptors and that dimaprit is an H3 receptor antagonist of moderate potency.

Mutual interaction of histamine H3-receptors and alpha 2-adrenoceptors on noradrenergic terminals in mouse and rat brain cortex.

Brain cortex slices were preincubated with 3H-noradrenaline and superfused with physiological salt solution containing desipramine. We studied the inhibition of the electrically evoked tritium overflow caused by histamine in the presence of alpha-adrenoceptor ligands (mouse and rat brain cortex), and the inhibition caused by talipexole (the former B-HT 920) in the presence of H3-receptor ligands (mouse brain cortex). In mouse brain cortex slices, the inhibitory effect of histamine on the tritium overflow evoked by 36 pulses, 0.3 Hz was not changed by the alpha 1-adrenoceptor antagonist prazosin, but increased by the alpha 2-adrenoceptor antagonist rauwolscine. When the current strength or the duration of electrical pulses was reduced to compensate for the increase in evoked tritium overflow produced by rauwolscine, the latter still enhanced the effect of histamine. The histamine-induced inhibition of tritium overflow evoked by 360 pulses, 3 Hz was not affected by the alpha 1-adrenoceptor agonist phenylephrine but attenuated by the alpha 2-adrenoceptor agonist talipexole. Finally, the inhibition by histamine of the tritium overflow evoked by 3 pulses, 100 Hz was attenuated by talipexole but not affected by rauwolscine. Conversely, the inhibitory effect of talipexole on tritium overflow elicited by 360 pulses, 3 Hz was slightly attenuated by the H3-receptor agonist R-(-)-alpha-methylhistamine but not affected by the H3-receptor antagonist thioperamide. In rat brain cortex slices, histamine only tended to inhibit tritium overflow evoked by 360 pulses, 3 Hz, both in the absence of alpha-adrenoceptor antagonists and in the presence of prazosin. However, histamine markedly inhibited the evoked overflow in the presence of rauwolscine.(ABSTRACT TRUNCATED AT 250 WORDS)