[Prostate cancer diagnosis using ultrasound elastography. Introduction of a novel technique and first clinical results]. / Prostatakarzinomdiagnostik durch UltraschallelastographieVorstellung eines neuartigen Verfahrens und erste klinische Ergebnisse.

During the last decade screening has improved prostate cancer detection. The main reason for this development is a better understanding of the margins of prostate-specific antigen (PSA) serum levels and the classification of PSA subtypes. In contrast, the introduction of transrectal ultrasound has not led to a measurable change in the prostate cancer detection rate. Our aim was to develop a novel ultrasound system for the acquisition of elastographic images of the prostate and evaluate the system regarding its clinical applicability. We used a technically modified conventional ultrasound system and analyzed the high-frequency ultrasonic data with a computer program. The first patient-based results suggest that elastography allows an accurate measurement of tumor size and localization in contrast to conventional transrectal ultrasound. Elastography visualizes different tissue elasticities to distinguish benign and cancerous tissue. Thus, we were able to even correctly classify prostate cancer lesions which are iso- or hyperechoic in B-mode sonography.

[Drug therapy of benign prostatic hyperplasia syndrome with alpha 1-receptor blockers. Basic principles and clinical results]. / Medikamentöse Therapie des benignen Prostatasyndroms mit alpha 1-Rezeptorblockern. Grundlagen und klinische Ergebnisse.

This article reviews the structure and function of the sympathetic nervous system controlling the myogenic tone of the bladder outlet. Therefore, the sympathetic nervous system is partially responsible for urinary outflow resistance. The alpha 1-adrenoceptor antagonists alfuzosin, doxazosin, tamsulosin, or terazosin are able to reduce bladder outflow resistance, which leads to significant relief of LUTS (20-65%) and improvement of urinary flow (1-4.3 ml/s) in patients with symptomatic BPH. Alpha 1-blocker treatment works irrespective of the severity of symptoms, degree of subvesical obstruction, or prostate size. A significant reduction of residual urine was observed only occasionally, but at least alfuzosin is able to reduce the incidence of acute urinary retention. This article presents the results of 39 randomized, placebo-controlled trials with 14,924 patients as well as trials with alpha 1-blockers and plant extracts or finasteride. The results of these trials indicate that all alpha 1-blockers are equally effective. However, tolerability of alfuzosin or tamsulosin is superior to doxazosin or terazosin. Furthermore, treatment of hypertension with doxazosin or terazosin is no longer recommended due to the increased frequency of cardiovascular side effects seen in the ALLHAT Study. As alpha 1-blockers can relieve symptoms and improve urinary flow more effectively than plant extracts or finasteride, alpha 1-blockers are the treatment of first choice in patients with symptomatic BPH without or with a minor degree of subvesical obstruction.

[alpha 1-receptor blockade in therapy of benign prostatic hyperplasia syndrome. Correct dosing for optimal effectiveness]. / alpha 1-Rezeptorenblockade zur Therapie des BPH-Syndroms. Richtige Dosierung für optimale Wirkung.

Four alpha 1-adrenoceptor antagonists are currently available for the medical treatment of lower urinary tract symptoms suggestive of benign prostatic obstruction in Germany: alfuzosin, doxazosin, tamsulosin, and terazosin. Indirect comparison based on randomized, placebo-controlled trials as well as several direct comparative studies have shown equal efficacy of all four drugs on urinary flow and symptom relief if suggested dosing regimens are applied. A dosing regimen below this recommendation should be restricted to those patients who have a proven satisfactory response to a lower dose.

Male lower urinary tract symptoms and related health care seeking in Germany.

OBJECTIVES: To investigate the prevalence of lower urinary tract symptoms (LUTS) and LUTS- related health care issues in the male population between the ages of 50 and 80 in Germany. METHODS: 8,973 randomly chosen men in the age group of interest received by mail a self-administered questionnaire addressing voiding symptoms and bother, common health status, and social demographic as well as health care resources related issues. RESULTS: Of 6,031 (67.2%) returned questionnaires, 5,404 (60.2%) were properly filled out and entered into the database. Of these, 5,004 (56%) completed all IPSS questions. 3,539 (70.7%) of the men presented with no or mild LUTS (IPSS 0--7), 1,465 (29,3%) with moderate to severe voiding symptoms (IPSS >7), respectively. From logistic regression analysis it appears that mainly bother from voiding symptoms as well as incomplete emptying and week stream induced a visit to the doctor. Of men with moderate symptoms (IPSS 8--19), 40% did not report any bother. CONCLUSION: LUTS is a common condition among German elderly males. In general, bother from LUTS seem to have more effects on health care seeking behavior than symptoms themselves or physical health status. Bother scores may discriminate between those individuals with moderate symptoms (IPSS 8--19), who may be followed through watchful waiting instead of active therapy.

Treatment of symptomatic benign prostatic hyperplasia with beta-sitosterol: an 18-month follow-up.

OBJECTIVES: To determine the long-term effects of phytotherapy with beta-sitosterol (the trade name for beta-sitosterol used in this study is Harzol(R)) for symptomatic benign prostatic hyperplasia (BPH). Patient and methods At 18 months after enrolment in a 6-month multicentre double-blind placebo-controlled clinical trial with beta-sitosterol (reported previously), patients were re-evaluated using the modified Boyarsky score, the International Prostate Symptom Score and quality-of-life index, the maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR). In this open extension of the original trial (after 6 months of treatment or placebo), patients were free to chose their further treatment for BPH. RESULTS: In all, 117 patients (59%) were eligible for analysis during the follow-up. Of the formerbeta-sitosterol group, 38 patients who continued beta-sitosterol treatment had stable values for all outcome variables between the end of the double-blind study and after 18 months of follow-up. The 41 patients choosing no further therapy had slightly worse symptom scores and PVR, but no changes in Qmax. Of the former placebo group, 27 patients who started beta-sitosterol after the double-blind trial improved to the same extent as the treated group for all outcome variables. The 18 patients choosing no further therapy showed no signs of improvement. CONCLUSION: The beneficial effects of beta-sitosterol treatment recorded in the 6-month double-blind trial were maintained for 18 months. Further clinical trials should be conducted to confirm these results before concluding that phytotherapy with beta-sitosterol is effective.

Management of the BPH syndrome in Germany: who is treated and how?

OBJECTIVES: To review the available data on contemporary management of symptomatic benign prostatic hyperplasia (BPH) within the German healthcare system. METHODS: Information was obtained from articles published in scientific journals retrieved through searches in Medline and Embase. In addition, preliminary data from the first representative German survey on lower urinary tract symptoms (LUTS) were obtained ('Herner LUTS-Study', a community-based survey in Herne, a city within the industrial complex called the Ruhr Area). Finally, the recently established German guidelines for the diagnosis and treatment of the BPH-Syndrom (BPS) were reviewed. RESULTS: Only few studies are published in the literature analysing the current concepts of management of BPH in Germany. These studies show that there is variation in the concepts of conservatory and surgical management of BPH. The German BPH guidelines suggest watchful waiting for patients with mild LUTS (total I-PSS < or = 7) and medical therapy or surgery for those with moderate to severe LUTS (I-PSS >7). There was no final consensus on the role of phytotherapy in the German treatment guidelines, due to the lack of clinical data. alpha(1)-Blockers and finasteride (for prostates >40 ml) are recommended medical treatment approaches. Transurethral resection of the prostate (TUR-P) is considered to be the standard surgical procedure. Preliminary data from the Herner LUTS-Study show, that approximately 30% of men aged 50-80 years have moderate to severe LUTS (i.e. total I-PSS score >7). About a third of these men currently seek healthcare. CONCLUSIONS: LUTS and BPS are a highly prevalent condition in Germany. With the estimate that the number of men over the age of 65 will almost double in Germany within the next 30 years, it will be a challenge in the next millennium to find the healthcare resources for the management of BPS. Copyrightz1999S. KargerAG,Basel

Cell turnover in human seminal vesicles and the prostate: an immunohistochemical study.

The human prostate and seminal vesicles are both androgen-dependent sex accessory organs. Their growth behavior, response to hormone manipulation, susceptibility to benign and malignant processes and sex accessory functions, however, differ greatly. The growth behavior of most tissues correlates well with the cell turnover rate of that tissue. Therefore, we compared the cell turnover of normal human prostate and seminal vesicles. Immunohistochemical expression of MIB-1 (proliferation), bcl-2 and transforming growth factor (TGF beta) were examined in 20 different samples taken from histologically normal human prostatic and seminal vesicle tissue. For the quantification of apoptosis, the TUNEL technique was used. The apoptosis rates in normal prostatic tissue (0.73+/-0.60) were significantly greater (P=0.003) than those seen in seminal vesicles (0.02+/-0.01). The proliferation rates also differed significantly (P=0.002) between these tissues (prostate: 0.77+/-0.78; seminal vesicles: 0.02+/-0.02). Eighty percent of the prostate tissue stained for bcl-2, whereas only 55% of the seminal vesicle tissue showed staining for bcl-2. All seminal vesicles and 75% of the prostate samples stained for TGF beta. For both androgen-dependent tissues, apoptotic rates closely equaled proliferation rates. The cell turnover, however, was much higher in the prostate than in the seminal vesicles. TGF beta seems to be more important for the regulation of cell turnover in the seminal vesicles than bcl-2. These differences in the proliferative behavior may explain why disturbances of apoptotic regulation lead to a more extensive net cell gain in prostatic tissue compared to the seminal vesicles. This might help explain the vastly different incidence of benign and malignant tumors in these organs.

Value of the Danish Prostate Symptom Score compared to the AUA symptom score and pressure/flow studies in the preoperative evaluation of men with symptomatic benign prostatic hyperplasia.

The Danish Prostate Symptom Score (DAN-PSS) is a new questionnaire for the assessment of lower tract urinary symptoms (LUTS), which claims to be able to predict bladder outlet obstruction. We evaluated the ability of the DAN-PSS to assess LUTS, to predict obstruction, and to predict treatment outcome in men with symptomatic uncomplicated BPH. Twenty-five consecutive men with symptomatic uncomplicated BPH filled in the AUA symptom score and the DAN-PSS and underwent uroflowmetry and pressure-flow studies prior to transurethral prostatic resection (TURP). Patients were reevaluated 4 days and 8 months after surgery. AUA score and DAN-PSS both assessed LUTS and were sensitive to symptom changes after therapy. Compared to pressure/flow studies, neither score correlated with bladder outlet obstruction. Peak urinary flow, however, correlated significantly with obstruction. None of the diagnostic tools used was able to improve patient selection for surgical treatment. The DAN-PSS is a valid and sensitive questionnaire for the assessment of LUTS. It is not able, however, to predict bladder outlet obstruction. In men with uncomplicated BPH, urodynamic evaluation of bladder outlet obstruction did not improve the subjective outcome of TURP.

Cyproterone acetate in the treatment of advanced prostatic cancer: retrospective analysis of liver toxicity in the long-term follow-up of 89 patients.

Cyproterone acetate (CPA) was the first steroidal antiandrogen used for the treatment of prostatic cancer. In recent studies CPA has been linked with DNA adduct formation and increased DNA repair synthesis in vitro, suggesting an increased risk for the development of hepatic malignancies. To assess liver-toxic and carcinogenic effects, 89 patients who received CPA 50 mg/day p.o. over 4 (range 2-152 months) years for prostatic cancer treatment were retrospectively evaluated. 22 patients (28.2%) showed elevated liver enzyme concentrations. In none of the 89 patients alpha-fetoprotein serum levels were elevated. In no case hepatocellular carcinoma has been observed, and in no case CPA administration was discontinued due to side effects. Considering the life expectancy of patients with advanced prostatic cancer and the long-term and high-dose exposure to CPA necessary to possibly induce liver tumors, it appears highly unlikely that CPA treatment may account for a substantial number of liver carcinomas in such patients.

Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group.

Medical treatments have become available for benign hypertrophy of the prostate, including alpha-receptor blocking agents and 5-alpha-reductase inhibitors. Drugs derived from plants, for which no precise mechanism of action has been described, are widely used for this purpose in Europe. In a randomised, double-blind, placebo-controlled multicentre study, 200 patients (recruited between April and October 1993) with symptomatic benign prostatic hyperplasia were treated with either 20 mg beta-sitosterol (which contains a mixture of phytosterols) three times per day or placebo. Primary end-point was a difference of modified Boyarsky score between treatment groups after 6 months; secondary end-points were changes in International Prostate Symptom Score (IPSS), urine flow, and prostate volume. Modified Boyarsky score decreased significantly with a mean of -6.7 (SD 4.0) points in the beta-sitosterol-treated group versus -2.1 (3.2) points in the placebo group p < 0.01. There was a decrease in IPSS (-7.4 [3.8] points in the beta-sitosterol-treated group vs -2.1 [3.8] points in the placebo group) and changes in urine flow parameters: beta-sitosterol treatment resulted in increasing peak flow (15.2 [5.7] mL/s from 9.9 [2.5] mL/s), and decrease of mean residual urinary volume (30.4 [39.9] mL from 65.8 [20.8] mL). These parameters did not change in the placebo group (p < 0.01). No relevant reduction of prostatic volume was observed in either group. Significant improvement in symptoms and urinary flow parameters show the effectiveness of beta-sitosterol in the treatment of benign prostatic hyperplasia.

Implication of cell kinetic changes during the progression of human prostatic cancer.

The daily percentage of cells proliferating and dying were determined for normal, premalignant, and cancerous prostatic cells within the prostate as well as for prostatic cancer cells in lymph node, soft tissue, and bone metastases from untreated and hormonally failing patients. These data demonstrate that normal prostatic glandular cells have an extremely low but balanced rate of cell proliferation and death (i.e., both <0.20%/day). This results in a steady-state, self-renewing condition in which there is no net growth, although the glandular cells are continuously being replaced (i.e., turnover) every 500 +/- 79 days. Transformation of these cells into high-grade prostatic intraepithelial neoplastic cells initially involves an unbalanced increase in the daily percentage of cells proliferating versus dying, such that net continuous growth occurs (i.e., mean doubling time, 154 +/- 22 days). As these early proliferation lesions continue to grow into late stage high-grade prostatic intraepithelial neoplastic cells, the daily percentage of cells dying increases further to a point equaling the daily percentage of proliferation. This results in cessation of net growth while inducing a 6-fold increase in the turnover time of these cells (i.e., 56 +/- 12 days), increasing their risk of further genetic changes. The transition of late stage high-grade prostatic intraepithelial neoplastic cells into localized prostatic cancer cells involves no further increase in proliferation but a decrease in death resulting in net continuous growth of localized prostatic cancers with a mean doubling time of >/=475 days. As compared to localized prostatic cancer cells, metastatic prostatic cancer cells within lymph nodes or bones of untreated patients have an increase in daily rate of proliferation coupled with a reduction in their daily percentage of cell death, producing net growth rates with a mean doubling time of 33 +/- 4 days and 54 +/- 5 days, respectively. Remarkably, there is no further increase in proliferation in hormonally failing patients, but instead an increase in the daily percentage of androgen-independent prostatic cancer cells dying within soft tissue or bone metastases. These changes result in doubling times which are two to three times longer (i.e., 126 +/- 21 and 94 +/- 15 days) in these lymph node and bone metastatic sites, respectively, compared to similar sites in hormonally untreated patients. These data demonstrate that the daily percentage of proliferation for either androgen-dependent or -independent metastatic prostatic cancer cells is remarkably low (i.e., <3. 0%/day), consistent with why antiproliferative chemotherapy has been of such limited value against such metastatic cells. These results also suggest that prostatic carcinogenesis starts in the second to third decade of life and may require over 50 years for progression to pathologically detectable metastatic disease.

Cell proliferation, DNA repair, and p53 function are not required for programmed death of prostatic glandular cells induced by androgen ablation.

Androgen ablation induces programmed death of androgen-dependent prostatic glandular cells, resulting in fragmentation of their genomic DNA and the cells themselves into apoptotic bodies. Twenty percent of prostatic glandular cells undergo programmed death per day between day 2 and 5 after castration. During this same period, < 1% of prostatic glandular cells enter the S phase of the cell cycle, documenting that > 95% of these die in G0. During the programmed death of these G0 glandular cells, a futile DNA repair process is induced secondary to the DNA fragmentation. This futile DNA repair is not required, however, since inhibition of this process by > 90% with an appropriately timed hydroxy-urea dosing regimen had no effect upon the extent of the programmed death of these cells after castration. Likewise, p53 gene expression is not required since the same degree of cell death occurred in prostates and seminal vesicles after castration of wild-type and p53-deficient mice.