Breza J; Dzurny O; Borowka A; Hanus T; Petrik R; Blane G; Chadha-Boreham H
Department of Urology, University Hospital, Bratislava, Slovak Republic.
Curr Med Res Opin (England) 1998, 14 (3) p127-39

Pygeum africanum extract is available as Tadenan in many countries, including those in central and eastern Europe, for the treatment of mild to moderate BPH. Its efficacy and acceptability have been demonstrated in numerous open and placebo-controlled studies in large populations. The present open three-centre efficacy and safety study was conducted according to common protocol at urology clinics in the Czech and Slovak Republics and in Poland, in order to confirm the therapeutic profile of Pygeum africanum in conditions of daily practice, using International Prostate Symptom Score (IPSS) and flowmetry assessments. Men aged 50-75 years and in compliance with the selection criteria (including IPSS > or = 12, quality of life (QoL) score > or = 3, and maximum urinary flow < or = 15 ml/s) were first examined then recalled after two weeks during which no treatment was provided (washout and check of stability). If still compliant, they were entered at this point into a two-month period of treatment with Pygeum africanum extract 50 mg twice daily. There followed a further one-month period without treatment, the objective being to evaluate the persistence of any effects observed during the previous two months of Pygeum africanum administration. The primary efficacy parameter investigated was IPSS; the other efficacy parameters were QoL, nocturnal frequency, maximum urinary flow, average urinary flow, post-voiding residual volume and prostatic volume, after one and two months of Pygeum africanum treatment and one month after stopping treatment. A total of 85 patients were evenly distributed between the three centres and completed the entire study. At inclusion their mean IPSS was 16.17, QoL was 3.60 and nocturia was 2.6 times per night. The changes in subjective scores, IPSS and QoL after the two-month treatment period were highly statistically significant with mean improvements of 40% and 31%, respectively. Nocturnal frequency was reduced by 32% and the mean reduction was again highly statistically significant. Mean maximum urinary flow, average urinary flow and urine volume were also statistically significantly improved, but the modest improvement in post-voiding volume did not reach statistical significance. The improvements, which exceeded those observed with placebo in earlier studies, were maintained after one month without treatment indicating an interesting persistence of clinically useful activity. Prostatic volume and quality of sexual life remained unchanged throughout. No treatment-related adverse effects were observed. In conclusion, under conditions of daily practice, Pygeum africanum extract induces significant improvement in IPSS and uroflowmetry parameters. These positive effects are accompanied by a very satisfactory safety profile with the overall result of a substantial improvement in QoL.

Lowe FC; Dreikorn K; Borkowski A; Braeckman J; Denis L; Ferrari P; Gerber G; Levin R; Perrin P; Senge T
Department of Urology, St. Luke's-Roosevelt Hospital, New York, New York 10019, USA.
Prostate Nov 1 1998, 37 (3) p187-93

BACKGROUND: In order to assess the efficacy of phytotherapeutic agents for the treatment of benign prostatic hyperplasia (BPH), a review of recently published double-blind placebo-controlled trials was undertaken.

METHODS: Only those studies reviewed by the Other Medical Therapies Committee of the Fourth International Consultation on BPH were included.

RESULTS: These studies suggest a possible benefit for the use of phytotherapeutic preparations in the treatment of BPH.

CONCLUSIONS: These studies need to be confirmed in larger long-term placebo-controlled studies in order to ascertain the true efficacy of these agents. (32 Refs.)

Geller J; Sionit L; Partido C; Li L; Tan X; Youngkin T; Nachtsheim D; Hoffman RM
AntiCancer, Inc., San Diego, California 92111, USA.
Prostate Feb 1 1998, 34 (2) p75-9

BACKGROUND: There is strong epidemiological evidence that prostate disease is significantly less prevalent in the Orient, where the intake of soy products is very high, than in the United States. We therefore undertook a study of the effects of genistein, a major component of soy, on growth of human-patient benign prostatic hypertrophy (BPH) and prostate cancer tissue in three-dimensional collagen gel-supported histoculture.

METHODS: Surgical specimens of human BPH and cancer were histocultured for 5 days to study the effects of genistein on growth, as measured by inhibition of 3H-thymidine incorporation per microgram protein on day 5.

RESULTS: Genistein in doses of 1.25-10 micrograms/ml decreased the growth of BPH tissue in histoculture in a dose-dependent manner, with little additional effect at higher doses. Prostate cancer tissue in histoculture was similarly inhibited by these doses of genistein.

CONCLUSIONS: Genistein decreases the growth of both BPH and prostate cancer tissue in histoculture. The data suggest that genistein has potential as a therapeutic agent for BPH and prostate cancer.

Breza J.; Dzurny O.; Borowka A.; Hanus T.; Petrik R.; Blane G.; Chadha-Boreham H.; Autet W.
Dr. W. Autet, Medical Affairs, Groupe Fournier, 153 rue de Buzenval, 92380 Garches France
Current Medical Research and Opinion (United Kingdom), 1998, 14/3 (127-139)

Pygeum africanum extract is avialable as Tadenan (R), including those in central and eastern Europe, for the treatment of mild to moderate BPH. Its efficacy and acceptability have been demonstrated in numerous open and placebo-controlled studies in large populations. The present open three-centre efficacy and safety study was conducted according to common protocol at urology clinics in the Czech and Slovak Republics and in Poland, in order to confirm the therapeutic profile of Pygeum africanum in conditions of daily practice, using International Prostate Symptom Score (IPSS) and flowmetry assessments. Men aged 50-75 years and in compliance with the selection criteria (including IPSS less than or equal to 12, quality of life (QoL) score less than or equal to 3, and maximum urinary flow less than or equal to 15 ml/s) were first examined then recalled after two weeks during which no treatment was provided (washout and check of stability). If still complaint, they were entered at this point into a two-month period of treatment with Pygeum africanum extract 50 mg twice daily. There followed a further one-month period without treatment, the objective being to evaluate the persistence of any effects observed during the previous two months of Pygeum africanum administration. The primary efficacy parameter investigated was IPSS; the other efficacy parameters were QoL, nocturnal frequency, maximum urinary flow, average urinary flow, post-voiding residual volume and prostatic volume, after one and two months of Pygeum africanum treatment and one month after stopping treatment. A total of 85 patients were evenly distributed between the three centres and completed the entire study. At inclusion their mean IPSS was 16.17, QoL was 3.60 and nocturia was 2.6 times per night. The changes in subjective scores, IPSS and QoL after the two-month treatment period were highly statistically significant with mean improvements of 40% and 31%, respectively. Nocturnal frequency was reduced by 32% and the mean reduction was again highly statistically significant. Mean maximum urinary flow, average urinary flow and urine volume were also statistically significantly improved, but the modest improvement in post-voiding volume did not reach statistical significant. The improvements, which exceeded those observed with placebo in earlier studies, were maintained after one month without treatment indicating an interesting persistence of clinically useful activity. Prostatic volume and quality of sexual life remained unchanged throughout. No treatment-related adverse effects were observed. In conclusion, under conditions of daily practice, Pygeum africanum extract induces significant improvement in IPSS and uroflowmetry parameters. These positive effects are accompanied by a very satisfactory safety profile with the overall result of a substantial improvement in QoL.

Schiebel-Schlosser G.; Friederich M.
G. Schiebel-Schlosser, SmithKline Beecham GmbH and Co. KG, Hermannstrasse 7, 77815 Buhl Germany
Zeitschrift fur Phytotherapie (Germany), 1998, 19/2 (71-76)

Therapeutic use and safety of a pumpkin seed extract were tested in a multicentric clinical triol with 2,245 patients suffering from benign prostatic hyperplasia (Stage I to II according to Alken). Urinary symptoms were recorded by the International-Prostate-Symptom-Score according to the American Urological Association (I-PSS), the influence on quality of life has been recorded by a quality of life questionnaire (LQ-Index). Patients were treated for 12 weeks with 1-2 capsules per day containing 500 mg of a pumpkin seed extract (15-25:1). The I-PSS decreased by 47,4%, life quality improved by 46,1% during therapy. More than 96% of the patients had no undesired side effects under the treatment with Prosta Fink Forte (R).

Jenner R.; Haertel S.
Dr. R. Jenner, Urologie Abteilung, Kaiserstrasse 15, 76131 Karlsruhe Germany
Therapie und Erfolg Urologie Nephrologie (Germany), 1998, 10/1-2 (48-51)

102 patients with benign prostatic hyperplasia stage I-II (Alken) were treated with a combined preparation of Sabal fruit and Urtica root extracts (PRO 160/120, Prostagutt (R) forte) in a 12-week multicenter open trial. The primary outcome variable of the study, the maximal urinary flow rate, was increased by a statistically highly significant mean value of 4,2 ml/s at the end of therapy. Almost all secondary outcome variables showed a statistically significant improvement after 12 weeks, too. Particularly the reduction of the residual urine volume by 26,3 ml on average is clinically relevant. Moreover, a clear improvement of the subjective condition of the patients was observed. Besides its good efficacy, the investigational drug was excellently tolerated by the patients, thus confirming its therapeutic suitability in the treatment of benign prostatic hyperplasia stage I-II (Alken).

Awang D.V.C.
Canadian Pharmaceutical Journal (Canada), 1997, 130/9 (37-44+62)

No abstract.

Weisser H, Krieg M
Institut fur Klinische Chemie, Transfusions- und Laboratoriumsmedizin, Berufsgenossenschaftliche Kliniken Bergmannsheil, Universitatsklinik der Ruhr-Universitat, Bochum.
Urologe A 1997 Jan;36(1):3-9

Although human benign prostatic hyperplasia (BPH) is the most common tumor in men, its etiology is still unclear. At present, it is only widely accepted that BPH is under the endocrine control of the testes and strongly associated with aging. Therefore, in the human prostate we describe the impact of aging on the activity of various androgen metabolizing enzymes as well as on the endogenous androgen and estrogen levels. Moreover, the inhibition of 5 alpha-reductase by finasteride (Proscar) will be reported. Among all androgen metabolizing enzymes, within the human prostate 5 alpha-reductase is the most powerful one. Most of the androgen metabolizing enzymes undergo a significant age-dependent alteration. For distinct enzymes, the correlation with age is either negative (e.g. 5 alpha-reductase), or positive. Despite a complex pattern of age-dependent alterations, the dominance of 5 alpha-reductase among all androgen metabolizing enzymes is always maintained. This is underlined by a strong accordance between the age-dependent 5 alpha-reductase activity and the corresponding age-dependent endogenous DHT level. In epithelium, both the 5 alpha-reductase activity and the DHT level decrease with age, whereas in stroma not only the 5 alpha-reductase activity is rather constant over the whole age range but the DHT level as well. In contrast to the relatively unaltered DHT content in the stroma of the human prostate, the estrogen content follows an age-dependent increase. On the other side, in epithelium such a positive correlation between the estrogen level and age is not found. Thus, the age-dependent decrease of the DHT accumulation in epithelium and the concomitant increase of the estrogen accumulation in stroma will lead to a tremendous increase with age of the estrogen/androgen ratio in the human prostate. This could be of pathogenetic importance for BPH development if in fact a balanced androgen/estrogen synergism is necessary for the integrity of the normal human prostate. Finally, it is remarkable that the inhibition of 5 alpha-reductase activity by finasteride (Proscar) is significantly stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finasteride treatment is primarily due to the regression of BPH epithelium.

Krieg M, Weisser H, Tunn S
BG-Kliniken Bergmannsheil-Universitatsklinik-Institut fur Klinische Chemie und Laboratoriumsmedizin, Bochum.
Verh Dtsch Ges Pathol 1993;77:19-24

Among all androgen metabolizing enzymes within the human prostate 5 alpha-reductase is the most powerful one. In the epithelium its activity decreases with age, while in the stroma it remains constant over the whole age range. Thus, in older prostates with benign hyperplasia the activity of 5 alpha-reductase is almost the same in both compartments. The same holds true for the DHT content, being highest in the epithelium of prostates from young men. With age it decreases to levels similar to those in the stroma. In contrast to DHT, estrogens are increasingly accumulated in the stroma with advancing age, while in the epithelium the estrogen level remains constant over the whole age range. The age-dependent decrease of the DHT level in the epithelium and the increase of the estrogen level in the stroma lead to a significant increase of the estrogen/androgen ratio. This could be of pathobiological importance for BPH development.

Krieg M, Nass R, Tunn S
Institute of Clinical Chemistry and Laboratory Medicine, University Clinic Bergmannsheil, Bochum, Germany.
J Clin Endocrinol Metab 1993 Aug;77(2):375-81

It is widely believed that benign prostatic hyperplasia (BPH) is associated with aging. Thus, the question arises whether or not a correlation exists between the well known prostatic androgen and estrogen accumulation and aging. To address this question, we measured 5 alpha-dihydrotestosterone (DHT), testosterone, estradiol, and estrone in epithelium and stroma of six normal (NPR) and 19 BPH and correlated the values with the age of the donors (26-87 yr). The mean DHT level in NPR epithelium was significantly higher than in NPR stroma, and also significantly higher than in epithelium and stroma of BPH. The epithelial DHT level of NPR and BPH decreased with age, the correlation being statistically significant. The stromal DHT level of NPR and BPH showed no correlation with age. Concerning testosterone, generally rather low values were found which showed no correlation with age. The mean levels of estradiol and estrone were significantly higher in BPH stroma as compared to BPH epithelium as well as to NPR epithelium and stroma. In NPR, the mean levels of estradiol and estrone were significantly higher in epithelium than stroma. In NPR and BPH, the stromal estradiol and estrone levels increased significantly with age. In epithelium such a correlation between the estrogen levels and age was not found. Our results indicate that the prostatic accumulation of DHT, estradiol, and estrone is in part intimately correlated with aging, leading with increasing age to a dramatic increase of the estrogen/androgen ratio particularly in stroma of BPH.

Kawamura H, Kimura M, Ichihara I
Department of Anatomy, Aichi Medical University, Japan.
Anat Anz 1993 Dec;175(6):569-75

After long-term castration, rats were injected with cotton seed oil, testosterone- and estradiol-17 beta-cypionate (CS, TC and EC). The height of the epithelial cells of the ventral prostates from the castrated rats increased after TC and EC-injection. The secretory and basal cells formed two layers of epithelium, an inner layer near the lumen with pale nuclei and another layer with dark nuclei. These two layers could result from a reduction of secretory epithelial cells. Castration decreased the ratio of secretory cells to basal cells (S/B). TC-injection increased the ratio of S/B because of the secretory epithelial cell growth. Longer dark cells may be transient cells, appearing during the differentiation of basal cells into secretory epithelial cells. A sheet branching off from the basal lamina was observed. Androgen may stimulate the synthesis of the lamina, but whether it induces the synthesis or turnover of the basal lamina has not been established. EC increased the ventral prostatic weight and secretory epithelial cell height and induced the appearance of crystalline granules. Increase in S/B ratio may result from an increase in the secretory epithelial cells, but not from basal cell multiplication due to squamous metaplasia. The ratio is significantly correlated to the weight of the ventral prostate, but not to the secretory epithelial cell height. Its value could indicate the multiplication of secretory epithelial cells, differentiation of basal cells into epithelial cells, or both. It is probable that basal cells do not change in number, but control the size of the rat ventral prostate in response to the hormone level.

Giovannucci E, Rimm EB, Chute CG, Kawachi I, Colditz GA, Stampfer MJ, Willett WC
Channing Laboratory, Department of Medicine, Harvard Medical School, Boston, MA.
Am J Epidemiol 1994 Dec 1;140(11):989-1002

Abdominal obesity increases the estrogen-to-androgen ratio and may increase sympathetic nervous activity, both hypothesized to influence the development of benign prostatic hyperplasia and the severity of urinary obstructive symptoms. In 1986 and 1987, men aged 40-75 years who were participants in the Health Professionals Follow-up Study and who were without prior diagnosis of cancer or prostatectomy provided data on weight, height, and waist and hip circumferences. The men were followed for incidence of prostatectomy for benign prostatic hyperplasia up to January 1992. In addition, the frequency and severity of symptoms of urinary obstruction were assessed among respondents to a questionnaire in 1992. Among 25,892 men who provided complete information for both surgery and symptoms, 837 men had surgery for benign prostatic hyperplasia, and 2,581 of those without surgery reported frequent urinary symptoms. After adjustment for age, smoking, and body mass index, abdominal obesity was related to prostatectomy (odds ratio (OR) = 2.38, 95% confidence interval (CI) 1.42-3.99, for those with a waist circumference > or = 43 inches (109 cm) relative to those with a waist circumference < 35 inches (89 cm); p trend < 0.0001) and with frequent urinary symptoms among those without prostatectomy (OR = 2.00, 95% CI 1.47-2.72; p < 0.0001). Body mass index, hip circumference, and waist-to-hip ratio were not associated with benign prostatic hyperplasia independently of waist circumference. These results suggest that abdominal obesity in men may increase the frequency and severity of urinary obstructive symptoms and may increase the likelihood that such obese men will undergo a prostatectomy.

Soygur T, Kupeli B, Aydos k, Kupeli S, Arikan N, Muftuoglu YZ
Department of Urology, University of Ankara, School of Medicine, Turkey.
Int Urol Nephrol 1996;28(1):55-9

In 68 men with benign prostatic hyperplasia, we evaluated the association between obesity and prostatic enlargement, as well as changes in serum levels of oestradiol, testosterone, dihydroepiandrosterone and dihydroepiandrosterone sulphate. Despite the larger adenomas, no increase in the symptom score for BPH was observed with increasing obesity. Average specimen weights increased with increasingly obesity and increasing host age from 46 to 80 g. We also found the serum oestradiol level significantly elevated in obese men who were 140% or over recommended weight compared to underweight men younger than 60 years (51.3 pg/ml versus 26.8 pg/ml, p < 0.01). This pattern was present in all age groups. These results indicate that obesity is a risk factor for prostatic enlargement but not for obstruction. Also the degree of obesity appears to have a direct effect on oestradiol levels through transformation of androgens in adipose tissue to oestrogens. In conclusion, further studies to evaluate the pathogenesis, pathophysiology, natural history and symptomatology of BPH would be of great interest and should help to define better the associations that we have recognized.

Daniell HW
Department of Family Practice, University of California Medical School, Davis.
J Urol 1993 Feb;149(2):315-7

In 379 men less than age 75 years who underwent initial transurethral prostatectomy for benign prostatic hypertrophy specimen weights were compared with host ages, obesity, smoking habits and the presence of incidental cancer. Among 334 men 60 to 74 years old average specimen weights increased with increasing obesity from 20.3 to 36.6 gm. Underweight men in comparison with men at least 30% overweight demonstrated more small specimens (10 gm. or less, 24% versus 2%, p < 0.001) and fewer large specimens (50 gm. or more, 5% versus 26%, p < 0.005). This pattern was present in smokers and nonsmokers. Adenoma weights increased with increasing host age and were larger in nonsmokers of all age groups. Body habitus was similar in the prostatectomy patients and 290 office patients of similar age, suggesting no increase in obstructive uropathy among obese men despite the larger adenomas. These observations are compatible with different risk factors for the obstructing and nonobstructing components of benign prostatic enlargement.

Hammarsten J, Hogstedt B
Urological Section, Department of Surgery, Varberg Hospital, Sweden.
Blood Press 1999;8(1):29-36

The purpose of this study was to test the hypothesis of a causal relationship between high insulin levels and the development of benign prostatic hyperplasia (BPH) and to determine the clinical, anthropometric, metabolic and insulin profile in men with fast-growing BPH compared with men with slow-growing BPH. The present study was designed as a risk factor analysis of BPH in which the estimated annual BPH growth rate was related to components of the metabolic syndrome. Two hundred and fifty patients referred to the Urological Section, Department of Surgery, Central Hospital, Varberg, Sweden, with lower urinary tract symptoms with or without manifestations of the metabolic syndrome were consecutively included. The prevalences of atherosclerotic disease manifestations, non-insulin-dependent diabetes mellitus (NIDDM) and treated hypertension were obtained. Data on blood pressure, waist and hip measurement, body height and weight were collected and body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn from fasting patients to determine insulin, total cholesterol, triglycerides, HDL and LDL cholesterol, uric acid, alanine aminotransferase (ALAT) and prostate-specific antigen (PSA). The prostate gland volume was determined using ultrasound. The median annual BPH growth rate was 1.04 ml/year. Men with fast-growing BPH had a higher prevalence of NIDDM (p = 0.023) and treated hypertension (p = 0.049). These patients were also taller (p=0.004) and more obese as measured by body weight (p<0.001), BMI (p=0.026), waist measurement (p <0.001), hip measurement (p = 0.006) and WHR (p=0.029). Moreover, they had elevated fasting plasma insulin levels (p = 0.018) and lower HDL cholesterol levels (p = 0.021) than men with slow-growing BPH. The annual BPH growth rate correlated positively with diastolic blood pressure (rs = 0.14; p = 0.009), BMI (rs = 0.24; p < 0.001) and four other expressions of obesity and fasting plasma insulin level (rs = 0.18; p = 0.008), and negatively with the HDL cholesterol level (rs = -0.22; p = 0.001). In conclusion, the data suggest that NIDDM, hypertension, tallness, obesity, high insulin and low HDL cholesterol levels constitute risk factors for the development of BPH. The results also suggest that BPH is a component of the metabolic syndrome and that BPH patients may share the same metabolic abnormality of a defective insulin-mediated glucose uptake and secondary hyperinsulinaemia, as patients with the metabolic syndrome. The findings support the hypothesis of a causal relationship between high insulin levels and the development of BPH, and give rise to a hypothesis of increased sympathetic nerve activity in men with BPH.

Cetinkaya M, Cetinkaya H, Ulusoy E, Baz S, Memis A, Yasa H, Yanik B, Ozturk B, Uzunalimoglu O
Department of Urology, Ankara Numune Hospital, Turkey.
Prostate 1998 Jul 1;36(2):80-4

BACKGROUND: The object of this study was to investigate the effects of hepatic cirrhosis on the development of benign prostatic hyperplasia and consequent effects on prostatic volume, serum prostate-specific antigen (PSA), and prostatism symptoms.

METHODS: Sixty patients with postnecrotic cirrhosis and alcoholic cirrhosis at age 40 and over, and 20 voluntary subjects in the same age group with normal hepatic functions, were evaluated with prostatic volume calculation by transrectal ultrasound, symptom scoring according to American Urology Association (AUA) criteria, measurement of serum prostate-specific antigen (PSA), serum total testosterone (TT), free testosterone (FT), estradiol (E2), and calculation of E2/FT ratios, and the results were analyzed statistically by the Mann-Whitney U-test.

RESULTS: Serum FT and TT levels were significantly lower in the hepatic cirrhosis group compared to the control group (P = 0.0000 and P = 0000, respectively). Though mean serum E2 level was a little higher in cirrhotic patients compared to controls, the difference was not significant; however, the higher E2/FT ratio in the cirrhotic group was statistically significant (P = 0.27 and P = 0.0002, respectively). In the cirrhotic group, the decrease in FT and TT levels was greater, as the disease advanced. While E2 and E2/FT ratio increase, correlate with poor prognosis, no statistically significant differences were found. Mean prostatic volume, serum PSA level, and total symptom score were significantly higher in the control group, compared to the cirrhotic group (P = 0.0001, P = 0.0006, and P = 0.002, respectively). Prostatic volume decreased parallel to severity of disease in cirrhotic patients.

CONCLUSIONS: The main reason for the decrease in mean prostatic volume in cirrhotic patients compared to subjects in the same age group with normal hepatic functions was the decrease in serum FT and TT levels, and the secondary cause was the increase in E2/FT ratio, indicating estrogenic predominance

Boehm S, Nirnberger G, Ferrari P
Department of Neuropharmacology, University of Vienna, Austria
Stefan.Boehm@univie.ac.at
Wien Klin Wochenschr 1998 Dec 11;110(23):817-23

Estrogen suppression has been introduced as a pharmacotherapeutic strategy in the medical treatment of benign prostatic hyperplasia. Recent negative results obtained in placebo-controlled trials with the aromatase inhibitor atamestane raised doubts about the efficacy of estrogen reduction. However, inhibition of aromatase not only reduces estrogens but also increases androgens which promote prostatic growth. In order to reevaluate the therapeutic efficacy of estrogen suppression, we summarize clinical trials investigating the therapeutic effects of mepartricin in the treatment of uncomplicated benign prostatic hyperplasia. Mepartricin has been reported to lower the levels of circulating estrogens without causing changes in other hormones such as androgens. By applying stringent inclusion criteria, 23 studies (including 7 placebo-controlled trials, 3 post-marketing surveillance studies, and 13 open trials) published between 1982 and 1996 were selected to be included in this report. In 79.9% of 4635 patients treated with mepartricin, its therapeutic effect was rated "good" or "excellent". In 6 out of 7 placebo-controlled trials, the therapeutic efficacy of mepartricin was significantly superior to that of placebo. Comparison of these data with results obtained with alpha 1-adrenoceptor antagonists or with the 5 alpha-reductase inhibitor finasteride indicates that mepartricin is as efficient as these widely accepted medical treatments for benign prostatic hyperplasia. Since mepartricin acts selectively upon estrogens, the present results show that estrogen suppression may be considered an efficient pharmacotherapeutic strategy in the medical treatment of uncomplicated benign prostatic hyperplasia.

Kawakami E, Shimizu M, Orima H, Fujita M, Hori T, Tsutsui T
Department of Reproduction, Nippon Veterinary and Animal Science University, Tokyo, Japan.
Int J Androl 1998 Apr;21(2):67-73

Eight beagles with benign prostatic hypertrophy (BPH) were treated by subcutaneous implantation of pellets containing 10 mg/kg chlormadinone acetate (CMA), a synthetic anti-androgen, plus daily oral administration of CMA at 2 mg/kg per day for 7 days as a therapy for BPH. Prostatic and testicular size were measured and prostatic and testicular biopsies were performed by laparotomy before and after CMA treatment. Plasma levels of luteininzing hormone (LH), testosterone and oestradiol were also measured. The clinical signs of BPH, for example haematuria and dysuria, resolved within 1 week of treatment. Mean prostatic volume decreased to 56% of the pretreatment value. At 40 weeks after treatment, prostatic volume had decreased by 36%. Histological examination of the prostate 1 week after treatment revealed reduction in diameter of the alveoli and in height of the glandular epithelium. Degeneration and atrophy of the glands were marked 4-12 weeks after treatment. In the testis, the diameter of seminiferous tubules and the number of germ cells in the seminiferous tubules had decreased markedly at 12 and 24 weeks after treatment. Although plasma LH concentrations did not undergo any marked fluctuations after CMA treatment, levels of testosterone and oestradiol were lower than before treatment. The results indicate that implantation of 10 mg/kg CMA, , plus 7-day oral administration of 2 mg/kg CMA, bring about resolution of the clinical signs and marked reduction in prostatic volume within 1 week of treatment.

Schweikert HU, Tunn UW
Department of Internal Medicine, University of Bonn, FRG.
Steroids 1987 Jul-Sep;50(1-3):191-200

The aromatase inhibitor testolactone was used for endocrine treatment of benign prostatic hyperplasia (BPH). Thirteen patients (mean age 79 years) with complete urinary retention (BPH stage IV) without improvement after 4 weeks of bladder drainage by suprapubic catheter were treated with testolactone 100 mg, b.i.d., for 6 months. Nine men (mean age 80 years) with identical conditions who did not receive hormonal therapy served as controls. Results, treatment group: In 7 patients spontaneous micturation reoccurred after an average treatment period of 8 weeks (group A); 6 patients continued to need the catheter (group B). Prostatic volume decreased in all patients, and an average volume reduction of 26% was found in group A, whereas in group B the decrease averaged 15%. Finally, the testosterone/estradiol ratio significantly increased in all patients during treatment. Control group: Prostatic volume did not change nor did spontaneous micturation occur during the whole observation period.

Vahlensieck W Jr, Fabricius PG, Hell U
Fortschr Med 1996 Nov 10;114(31):407-11

PH patients with Vahlensieck stage II or III disease are suitable for drug treatment. The points of attack are reduction of testosterone, conversion of testosterone to dihydrotestosterone, conversion of testosterone to estrogen using GnRH analogues, antiandrogens and alpha reductase inhibitors or aromatose inhibitors. Furthermore a reduction in obstruction is achieved through the use of phytopharmaceuticals containing 5-lipoxygenase and cyclooxygenase inhibitors. At present, Curcurbitae pepo seeds, Urtica dioica root, Pollinis siccae extract and Sabal serrulata seed extract are approved for the treatment of prostatic diseases in Germany. The use of alpha-1-sympathicolytic treatment may reduce muscular tone in the prostate. Combination of the various modes of action may also offer an effective form of treatment.

Continued on the next page...

Comparison of androgen-independent growth and androgen-dependent growth in BPH and cancer tissue from the same radical prostatectomies in sponge-gel matrix histoculture.

Geller J; Partido C; Sionit L; Youngkin T; Nachtsheim D; Espanol M; Tan Y; Hoffman R
Department of Medical Education, Mercy Hospital and Medical Center, San Diego, CA 92103-2180, USA.
Prostate (United States) Jun 1 1997, 31 (4) p250-4

BACKGROUND: In order to determine androgen sensitivities of prostate cancer and benign prostatic hypertrophy (BPH) tissues from the same patient in vitro, we used a histoculture technique to measure androgen-independent and androgen-dependent growth and compared them in paired specimens of BPH and prostate cancer from 23 radical prostatectomies. Both androgen-independent growth and androgen-dependent growth are measures of important biological characteristics of benign and malignant prostate tissue.

METHODS: The effect of hydroxyflutamide and antiandrogens on dihydrotestosterone (DHT)-stimulated incorporation of 3H-thymidine into both paired specimens of BPH and cancer was utilized to measure androgen-independent and androgen-dependent growth. The percentage decrease in 3H-thymidine incorporation/microgram protein in the flutamide-treated specimen compared to the DHT-treated specimen represented androgen-dependent growth. Residual 3H-thymidine incorporation/microgram protein during hydroxyflutamide administration represented androgen-independent growth.

RESULTS: Androgen-independent growth was significantly greater (P = 0.015) in the BPH compared to the cancer paired tissue. Androgen-dependent growth was significantly higher in 23 paired specimens of cancer compared to BPH (P < 0.03).

CONCLUSIONS: In paired specimens of BPH and prostate cancer from the same radical prostatectomy specimen, androgen-independent growth appeared greater in BPH compared to cancer specimens; androgen-dependent growth, however, was greater in prostate cancer than in BPH. There was no correlation of either growth parameter with Gleason tumor grade. Future clinical correlations will indicate whether either growth parameter represents an important prognostic factor for prostate cancer aggressiveness stimulated 3H-thymidine incorporation into DNA.

Alpha-1 adrenoceptor subtypes (high, low) in human benign prostatic hypertrophy tissue according to the affinities for prazosin.

Takeda M; Hatano A; Komeyama T; Koizumi T; Mizusawa T; Kanai T; Tomita Y; Maruyama K; Nagatomo T
Department of Urology, Niigata University, School of Medicine, Japan.
Prostate (United States) Jun 1 1997, 31 (4) p216-22

BACKGROUND: A novel classification of alpha-1 adrenoceptor subtypes (High, Low) was applied to human benign prostatic hypertrophy (BPH) tissue.

METHODS: Human BPH specimens were examined by a radioligand binding assay method using 3H-prazosin, and those data were compared with preoperative therapies.

RESULTS: (1) Scatchard analysis showed a high-affinity site (Kd:27.18 +/- 6.41 pM; Bmax:9.29 +/- 0.98 fM/mg protein; mean +/- SE) as alpha 1H, and a low-affinity site (Kd: 4088.0 +/- 744.34 pM, Bmax: 140.81 +/- 19.98 fM/mg protein) as alpha 1L subtype, for prazosin. (2) The Kd and Bmax were not different in the nontreated group (n = 5), alpha 1 blocker group (n = 5), and antiandrogen group (n = 5), in either alpha 1-high affinity or alpha 1-low affinity subtype. (3) Phenoxybenzamine had different pKi values for the above two adrenoceptor subtypes. Scatchard analysis showed that alpha 1-high affinity binding site disappeared in the presence of 1 microM of phenoxybenzamine, and the Kd and Bmax values in the presence of 1 microM of phenoxybenzamine were almost identical to the alpha 1-low affinity site of the two subtypes.

CONCLUSIONS: Human BPH tissue possesses both alpha 1H- and alpha 1L-adrenoceptor subtypes according to the affinities for prazosin, and only the alpha 1H subtype can be completely inhibited by some concentration of phenoxybenzamine. Treatment by alpha 1 blocker may not change the conditions of alpha 1-adrenoceptors in prostatic tissue.

[Urethral opening pressure: its clinical significance in prostatic obstruction]

Ameda K; Kobayashi S; Matsuura S; Sasaki Y; Shibata T; Koyanagi T
Department of Urology, Hokkaido University School of Medicine.
Nippon Hinyokika Gakkai Zasshi (Japan) Apr 1997, 88 (4) p496-502

BACKGROUND: In the evaluation of prostatic obstruction by using the pressure-flow study (PFS), we defined intravesical pressure at initiation of voiding as urethral opening pressure. This simple parameter could reflect the degree of compressive prostatic obstruction to some extent. The aim of this study is to analyze if a correlation exsists between clinical signs and urethral opening pressure, and if they bear any prognostic value in postoperative outcome of the patients.

METHODS: We analyzed 46 patients with clinical benign prostatic hypertrophy who underwent urodynamic evaluations including PFS. They were divided into 2 groups according to their urethral opening pressure. The high opening pressure was defined as greater than 70 cm water, which was noted in 24 patients (group A). Twenty-two patients had lower opening pressure (group B). Comparison of the clinical findings in these patients were reviewed. Medium-filling cystometry and PFS were performed transurethrally, by using a microtip transducer and rectal balloon. Cystoscopy was performed when possible, wherein we could examined the presence or absence of detrusor trabeculation. Transurethral prostatectomy was indicated in a total of 26 patients (16 in group A and 10 in group B), in whom postoperative clinical findings were analyzed with regard to the difference in preoperative urethral opening pressure. The patients who void with straining or who void following uninhibited detrusor contraction were excluded from this study.

RESULTS: International Prostatic Symptoms Score (I-PSS) revealed no significant difference in both groups, however, patients in group A were often suffering from urge incontinence preoperatively. Significant correlation was found among the incidence of detrusor instability, detrusor trabeculation and increased opening pressure. In PFS the patients with high opening pressure tended to have higher detrusor pressure at maximum flow and greater contractile power of the detrusor in voiding. There were no difference in Qmax and residual volume both groups. Postoperatively, symptomatic improvement was significant in both groups. There was no statistical difference in postoperative I-PSS between group A and B. Although 6 patients in group A demonstrated poor urinary control at 1 month, only two patients remained incontinent at 6 months postoperatively. As to urodynamic findings, the difference in PFS were markedly reduced between both groups. No difference was noted in postoperative Qmax as well.

CONCLUSION: Significant difference was found in preoperative objective findings except the flow rate between the patients with and without high urethral opening pressure, while no symptomatic difference was noted except urege incontinence in both groups. No prognostic value was demonstrated in urethral opening pressure, however, poor postoperative urinary control was often associated with initial high opening pressure in the short term. It was suggested that 1) compensatory detrusor hyperactivity improved voiding efficacy in the patients with prostatic obstruction, which was gradually normalized after the relief of obstruction, 2) symptomatic improvement was highly related to the relative improvement of the obstructive findings on PFS.

Free and total serum PSA values in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer and BPH. Is F/T PSA a potential probe for dormant and manifest cancer?

Tarle M; Kraljic I
Department of Oncology and Nuclear Medicine University Hospital Sestre Milosrdnice, Zagreb, Croatia.
Anticancer Res (Greece) May-Jun 1997, 17 (3A) p1531-4

Free and total PSA serum concentrations were retrospectively measured in 106 subjects: 45 patients with intraepithelial prostatic neoplasia (PIN), 30 subjects with benign prostatic hypertrophy (BPH) and 31 subjects with untreated prostatic carcinoma. The (F/T) x 100 PSA value is recorded in subjects with the elevated total PSA level (> 4 ng/ml). PIN patients were divided into two groups: a low grade PIN (PIN 1) and high grade PIN (PIN II-III) patients. The mean (F/T) x 100 PSA value in low grade PIN patients was 27.9 +/- 16.2 (range 17.1-41.2, median 25.1) and has been numerically similar to the respective value in BPH subjects (29.1 +/- 13.2, 15.8-48.0, 27.7). These parameters differed markedly (P < 0.01) from the mean (F/T) x 100 PSA value in high grade PIN patients (16.9 +/- 9.0, range 9.9-24.9, median 16.5). The later values were in turn comparable (P > > 0.05) with the respective value measured in untreated prostate cancer patients (14.4 +/- 10.8, 6.6-21.4, 12.6). Hence, values derived from the measurement of free and total serum PSA level may distinguish low grade PIN that prevailingly remains latent disease from high grade PIN that is in most cases not only early prostatic carcinoma but that is often a precursor of an aggressive neoplasm. The published literature is incoherent regarding the influence of tumor spread on F/T PSA level. The cutoff point that divides BPH from cancer may depend on tumor stage. We have not investigated F/T PSA values related to different stages and grades of prostate cancer. The cutoff point of (F/T) x 100 PSA in our study that divides malignant from benign prostate, or latent from manifest cancer, was tentatively assigned as 18 with a specificity of 91% and selectivity of 69%. Our data are based on the application of the CIS assay that, according to the literature, gives higher F-PSA % compared to other respective kits.

Optimising the medical management of benign prostatic hyperplasia.

McDermott T
Department of Urology, Meath Hospital, Dublin, Eire.
Br J Clin Pract (England) Mar 1997, 51 (2) p116-8

The ageing population is presenting an increasing demand on future healthcare services. In males, prostatic disease is one of the commonest disorders contributing to this. Alternatives to surgical intervention have to be considered as the preferred option for individuals and whether this be a therapeutic or a financial option to be taken. Two major medical alternatives are alpha-blockers and 5-alpha reductase inhibitors. The results of such treatment can be very beneficial in selected groups of patients. Side-effects with improved drugs electivity are reducing. Overall, while surgery still holds the gold standard, medical therapy has a significant role in the treatment of benign prostatic hypertrophy. Cost analysis may be a factor in deciding which treatment to have.

[Inferior vena cava obstruction syndrome caused by urinary retention]

Arruti A; Plazaola I; Mata J; Amato E
Arch Esp Urol (Spain) Jan-Feb 1997, 50 (1) p61-2

OBJECTIVE: To report an unusual case of inferior vena cava obstruction secondary to urinary retention.

METHODS/RESULTS: A 72-year-old male patient with a history of bilateral inguinal hernia and a recent hip surgery, presented with deep venous thrombosis in the left leg. A CT scan disclosed significant thickening of the bladder wall and grade III-IV hypertrophy of the prostate. Abdominal ultrasound disclosed a cystic mass compressing the vena cava and moderate ureterohydronephrosis. Edema spontaneously resolved following insertion of a urethral catheter and renal function returned to normal.

CONCLUSION: Obstruction of the inferior vena cava secondary to an enlarged bladder is rare. To our knowledge only two such cases have been reported in the literature. In the case described herein, urinary retention may have been exacerbated by prostatic hypertrophy, anesthesia and bed confinement due to hip surgery.

[Diagnostic efficacy of free PSA/total PSA ratio in the diagnosis of prostatic carcinoma]

Minardi D; Recchioni A; Baldassari M; Governatori D; Giammarco L; De Sio G; Muzzonigro G; Polito M
Clinica Urologica, Universita degli Studi, Ancona.
Arch Ital Urol Androl (Italy) Feb 1997, 69 Suppl 1 p93-5

Prostate specific antigen, specific organ and tissue marker, is a glycoprotein present in serum in different molecular forms, i.e. not protein bound and bound to proteins (PSA-ACT and PSA-AMG). The total PSA is expressed by the sum of the non protein bound value (free-PSA) and PSA-ACT. The aim of our study was to evaluate the hypothesis that measurement of free/total PSA ratio may be helpful in the differential diagnosis of prostatic pathology. Our study was conducted on 350 patients, to whom the total-PSA, free-PSA and f/t PSA had been performed; 250 patients showed a total PSA between 2.5 and 10 ng/ml and 185 of them had symptoms of bladder out-flow obstruction. In all of the 250 patients digital rectal examination, transrectal ultrasound and prostatic biopsy were performed. 100 patients were controls. The cut-off to differentiate between benign and malignant prostatic disease was 16%. The pathologic diagnosis was related to the f/t PSA ratio, and in particular those patients with a f/t PSA lower than 16% were expected to be prostatic carcinoma, while those with a f/t PSA higher than 16% were expected to be benign prostatic hypertrophy. The diagnostic accuracy of the ratio was calculated, and it was observed that it was 88.65% in the diagnosis of benign prostatic hypertrophy, while in the diagnosis of prostatic carcinoma it was 84.5%. We can therefore assume that f/t PSA can add useful information on prostatic pathology, eventually sparing unnecessary prostatic biopsies.

[Laser-assisted endoscopic resection: a new surgical technique for the treatment of benign prostatic hypertrophy. Preliminary results of a study involving 100 patients]

Albert P; Bretheau D; Taverna GL; Aimino R; Morin N; Salvo A
Reparto di Urologia, Fondazione S. Joseph, Marsiglia, Francia.
Arch Ital Urol Androl (Italy) Feb 1997, 69 (1) p15-21

This study was designed to assess the efficiency of 2 kind of laser prostatectomy devices in the treatment of Benign Prostatic Hyperplasia: a non contact technique versus a contact technique versus a contact one. From January 1994 to September 1994, 100 patients were included in a randomized comparison of 2 laser prostatectomy devices with right angle firing laser fibers: a non contact technique with Urolase fiber (Bard) (50 patients) versus a contact technique with Fibertom fiber (Dornier) (50 patients). The Urolase fiber was used at 60 Watts power setting for 60 seconds and administered to each lobe at 2, 4, 8 and 10 o'clock positions. The Fibertom fiber was used by dragging or the so called "painting" technique at 3 and 6 months with 3 parameters: Madsen symptom scores, peak urinary flow rates and post-void residual urine volumes. Operative morbidity rate was 9%. No difference in morbidity between both fibers. No blood transfusion was required in any case. Statistical analysis of the aforementioned parameters shows a p-value of < 0.001 for all parameters. Comparing the 2 different fibers, there was no statistical difference in outcome for any of these parameters. From this study we conclude that the preliminary results achieved, using the Urolase and the Fibertom fiber, are equivocal and interesting. However, a long term follow-up is necessary to evaluate the definitive efficiency of laser prostatectomy and to determine the optimal procedure.

Blood haemoglobin and the long-term incidence of acute myocardial infarction after transurethral resection of the prostate.

Hahn RG; Nilsson A; Farahmand BY; Persson PG
Department of Anaesthesia, South Hospital, Stockholm, Sweden.
Eur Urol (Switzerland) 1997, 31 (2) p199-203

OBJECTIVES: To study risk factors for acute myocardial infarction (AMI) in men suffering from benign prostatic hypertrophy.

METHODS: We followed 811 patients who underwent transurethral resection of the prostate (TURP) between 1983 and 1992 until the end of 1993 with regard to the incidence of AMI. The association between AMI and various potential risk factors was evaluated by epidemiological methods.

RESULTS: Fifty-two patients developed a first-time AMI after TURP. A pre-operative blood haemoglobin concentration in the range of 100-129 g/l (normal range 130-165 g/l) was associated with an increased long-term relative risk of a first-time AMI, which was estimated to be 2.0 (95% confidence interval = 1.0-4.1). This estimate became slightly stronger when we also included the 76 patients with a first AMI before surgery, 10 of whom developed a re-infarction after TURP. Furthermore, it was largely unchanged on adjusting for impaired health status and age > or = 75 years (patient factors) and for fluid absorption > or = 500 ml and a blood loss > or = 275 ml (operative factors), which had been reported to increase the long-term risk of AMI in a previous study.

CONCLUSION: A moderately reduced blood haemoglobin level before TURP is associated with a doubled risk of developing AMI in later life.

Insulin-like growth factor-binding protein-2 in patients with prostate carcinoma and benign prostatic hyperplasia.

Ho PJ; Baxter RC
Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, NSW, Australia.
Clin Endocrinol (Oxf) (England) Feb 1997, 46 (2) p145-54

OBJECTIVE: Insulin-like growth factor-binding protein (IGFBP)-2 is a major prostatic IGFBP and may be involved in regulating prostate growth. Patients with prostate carcinoma (PC) have elevated serum IGFBP-2 levels which correlate with the specific PC marker, prostate-specific antigen (PSA). The aims of this study were to investigate whether elevated serum IGFBP-2 is unique to PC or also occurs in benign prostatic hyperplasia (BPH), to examine the relations among age, PSA and IGFBP-2 levels, and to examine longitudinal changes in serum IGFBP-2 with PSA in prostate carcinoma.

DESIGN AND PATIENTS: Sixteen patients (61-83 years) with inoperable PC attending the oncology unit at a tertiary referral hospital were studied. Some serum samples were obtained retrospectively while the majority were collected prospectively over 13 months of treatment. The patients with PC were compared to 8 patients (66-73 years) with histologically proven BPH and 7 male control subjects (61-82 years) with no known prostate abnormality.

MEASUREMENTS: A new IGFBP-2 RIA was developed. Serum PSA (by EIA), and IGFBP-2, IGFBP-3, IGF-I and IGF-II (by RIA) were measured in all subjects, and serially in patients with PC.

RESULTS: Serum IGFBP-2 was significantly higher in PC with high PSA (560 +/- 66 micrograms/l, n = 12) than PC with normal PSA (292 +/- 65 micrograms/l, n = 4, P = 0.02), BPH (364 +/- 61 micrograms/l, P = 0.03) and controls (367 +/- 44 micrograms/l, P = 0.04). Mean IGFBP-2 in BPH was not different from controls. IGFBP-2 and PSA were significantly correlated with age (r = 0.543 and r = 0.433 respectively) and with each other even when the age effect was removed. Serum IGFBP-2 and PSA levels changed concordantly in all 7 PC patients who had serial sampling. Serum IGF-II but not IGF-I or IGFBP-3 was higher in PC and BPH than in controls (PC 332 +/- 23 micrograms/l), BPH 359 +/- 26 micrograms/l vs controls 241 +/- 37 micrograms/l; P = 0.03 and 0.02 respectively).

CONCLUSIONS: Serum IGFBP-2 levels are uniquely elevated in active prostate carcinoma but not in benign prostatic hypertrophy. In PC, serum IGFBP-2 levels closely parallel those of PSA and probably reflect tumour burden. The relation between PSA and IGFBP-2 is partially independent of their individual relations with age. Although serum IGFBP-2 is less sensitive than PSA in PC, it may have adjunctive value in the management of prostate carcinoma.

[Ureteral jet in patients with benign prostatic hypertrophy: prognostic evaluation during single and combined therapy]

Sperandeo M; Sperandeo G; Carella M; Bianco G; Cera A; Scarale MG; Viola M
Divisione di Medicina Interna, IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG.
Arch Ital Urol Androl (Italy) Dec 1996, 68 (5 Suppl) p175-8

By color-Doppler ultrasound it's possible to visualize urine flow jet from ureter into the bladder. Aim of the study was to evaluate of ureteral jet in patients with benign prostatic hyperplasia before, during and after with one or two drugs medical therapy. Thirteen patients, aged 51-63 years, were studied; they were not affected by metabolic, hepatic, renal diseases and by prostate inflammation. Eco color Doppler p.w. (Toshiba SSA 270A) with a convex probe of 3.5 MHz was used. A transabdominal ultrasound study was performed, prostate volume measured and ureteral jet visualized before and along treatment (at six months interval) with Finasteride and at the end of treatment. Successively, in four patients, with relapse of prostatic synptomatology, a transabdominal ultrasound study was performed, before and along a treatment with Finasteride, 5 mg/die (Finastid, Neopharmed) and Terazosin hydrochloride, 5 mg/die (Teraprost, Malesci), and at the end of treatment.

[Laser treatment of benign prostatic hypertrophy: the correlation of histologic results to nuclear magnetic resonance imaging]

Sulser T; Jochum W; Huch Boni RA; Briner J; Krestin GP; Hauri D
Urologische Klinik and Poliklinik, Universitatsspital Zurich.
Ann Urol (Paris) (France) 1997, 31 (1) p19-26

Minimally invasive treatments for benign prostatic hyperplasia (BPH) are currently very controversial. Nd:YAG laser transurethral thermocoagulation of the prostate is the technique most frequently used. The objective of this study was to assess the correlation between the morphological effects observed and the changes visible on magnetic resonance imaging during this type or treatment in the human prostate, in order to evaluate the tissue effects obtained according to the power and the interaction time applied. In 10 patients requiring radical prostatectomy for urological cancer, visual laser ablation of the prostate (VLAP) was performed during the 10 days preceding the radical operation (range: 1 to 9 days). The entire gland was submitted to pathological examination in order to correlate the histological result with contrast magnetic resonance imaging performed in 6 patients, using a standard transrectal coil, 12 to 24 hours before complete resection of the prostate. The morphological examination showed zones of periurethral necrosis of variable volume, accompanied by extensive peripheral haemorrhage, containing vessels with a partially obliterated lumen. Contrast magnetic resonance imaging (T1) showed that laser-induced lesions had a low density appearance and were perfectly demarcated with peripheral heterogeneous and hyperdense zones. In contrast with the experimental investigations performed to date, we demonstrated a clearly delayed tissue effect. Our experience demonstrates that a period of several hours between laser treatment and removal of the operative specimen is not sufficient to evaluate the extent of laser-induced lesions. High resolution magnetic resonance imaging with a standard transrectal coil, sometimes combined with a multiple coil, is very valuable to assess the effects of laser.

[Laser-tissue interactions in urology]

Mordon S
INSERM U279, Pavillon Vancostenobel, CHU de Lille.
Ann Urol (Paris) (France) 1997, 31 (1) p11-8

The laser-tissue interaction is a complex phenomenon which is usually classified into 4 distinct mechanisms: electro-mechanical action, photoablative action, thermal action and photochemical action. Fragmentation of calculi by means of a pulsed dye laser is a good example of the electro-mechanical action. The thermal action can induce coagulation and/or volatilisation of tissues. Treatments of bladder tumors, urethral strictures and more recently benign prostatic hypertrophy are based on the laser terminal action.

Effect of Serenoa repens extract (Permixon) on estradiol/testosterone-induced experimental prostate enlargement in the rat.

Paubert-Braquet M; Richardson FO; Servent-Saez N; Gordon WC; Monge MC; Bazan NG; Authie D; Braquet P
BIO-Inova EuroLab Research Labs, Plaisir, France.
Pharmacol Res (England) Sep-Oct 1996, 34 (3-4) p171-9

The effect of the lipidosterolic extract of Serenoa repens (LSESR) on experimental prostate enlargement was investigated in three groups of rats: shams treated with LSESR (sham rats), castrated animals treated with estradiol and testosterone (castrated rats), castrated animals treated with estradiol/testosterone and treated with LSESR (castrated and treated rats). Following three months of continuous hormonal treatment, the weight of prostates in estradiol/testosterone-treated castrated rats was significantly increased in comparison with sham-operated rats. Such an increase started rapidly, reached a maximum by 30 days and remained at a plateau or slightly declined thereafter. The increase of prostate total weight induced by the hormone treatment was inhibited by administration of LSESR. Indeed, the weight was significantly lower at day 60 and day 90 for the dorsal and lateral regions of the prostate. The weight of the ventral region of the prostate was significantly lower after 30 and 60 days treatment with LSESR. These results demonstrate that administering LSESR to hormone-treated castrated rats inhibits the increase in prostate wet weight. This effect of LSESR may explain the beneficial effect of this extract in human benign prostatic hypertrophy.

Immunohistochemical analysis of beta-tubulin isotypes in human prostate carcinoma and benign prostatic hypertrophy.

Ranganathan S; Salazar H; Benetatos CA; Hudes GR
Department of Medicine, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Prostate (United States) Mar 1 1997, 30 (4) p263-8

BACKGROUND: beta-tubulin, the intracellular target of several antimicrotubule agents, is encoded by at least six genes and exists as multiple isotypes with tissue-specific expression. Previous in vitro studies indicated that tubulin isotype composition may affect polymerization properties, dynamics, and sensitivity to drugs.

METHODS: To investigate the isotype composition of beta-tubulin in human prostate, tissues were collected from 26 patients after radical prostatectomy and sections were stained with isotype-specific antibodies.

RESULTS: beta IV tubulin is the predominant isotype in benign prostatic hyperplasia (BPH) and adenocarcinoma, showing significantly stronger immunohistochemical expression than beta II and beta III, particularly in Gleason's grade 3 and 4 cancers. Staining for the beta II isotype was invariably weak and often absent in BPH and normal glands. There was a marked increase in beta II isotype stain from BPH to cancer in 77% of the patients, suggesting that the expression of this isotype is related to malignant status.

CONCLUSIONS: The beta II tubulin isotype is a potential marker for prostate adenocarcinoma. The possibility that tumor beta-tubulin isotype composition may effect the response to antimicrotubule drug therapy in prostate cancer and other tumors merit investigation.

[LH-RH agonists as therapeutic alternative in patients with benign prostatic hyperplasia (BPH) and surgical contraindication. Long term follow up]

Granados Loarca EA; Chechile Toniolo G; Villavicencio Mavrich H
Servicio de Urologia., Fundacion Puigvert, IUNA, Barcelona, Espana.
Arch Esp Urol (Spain) Nov 1996, 49 (9) p923-7

OBJECTIVES: The purpose of this study is to describe the benefits afforded by treatment with LH-RH analogues to patients with physical or mental disorders that consult for acute urinary retention or urinary symptomatology secondary to benign prostatic hypertrophy (BPH).

METHODS: 52 patients with BPH in whom surgery was contraindicated due to poor mental or physical condition were treated with LH-RH analogue for six consecutive months a year for a period of three years. Thirty-eight patients had acute urinary retention and 14 had prostatic symptomatology.

RESULTS: Serum testosterone fell below 11 nmol/l. No significant changes in PSA levels were observed. Assessment of the prostate by DRE and US showed prostatic size had diminished. Voiding and postvoid residual urine improved and the bladder catheter could be withdrawn.

CONCLUSIONS: Our results show that treatment with LH-RH analogue can reduce the urinary symptoms and improve the quality of life of patients with BPH in whom surgery is contraindicated.

c-erbB-2 oncoprotein: a potential biomarker of advanced prostate cancer.

Arai Y; Yoshiki T; Yoshida O
Department of Urology, Kyoto Universit, Japan.
Prostate (United States) Feb 15 1997, 30 (3) p195-201

BACKGROUND: Overexpression of the c-erbB-2 oncogene has been implicated in the development and/or prognosis of several human carcinomas, including that of the prostate. Recently, c-erbB-2 protein was found to be released in the circulation. The present study was undertaken to study the significance of serum c-erbB-2 protein determination in men with prostate cancer.

METHODS: Serum c-erbB-2 protein determination was performed via immunoradiometric assay using two monoclonal antibodies that react with the extracellular domain of the protein. The study population consisted of 71 untreated prostate cancer patients. Of those, 33 with stage D2 disease entered a follow-up study. As control, serum c-erbB-2 protein levels were determined in 92 patients with benign prostatic hypertrophy. In addition, elevations of c-erbB-2 protein were examined in patients with various disease statuses: clinically well controlled (28 patients), disease progression (24 patients), and end-stage disease (17 patients).

RESULTS: Elevation of serum c-erbB-2 protein level was observed in patients in advanced stages, such as stage D2 disease (30%), disease progression (42%), and end-stage disease (82.4%). In the follow-up study, patients with an elevated c-erbB-2 level had a significantly shorter interval to disease progression than did those with a normal level.

CONCLUSIONS: The results suggest that c-erbB-2 can be used as a biomarker to identify a malignant subgroup in prostate cancer.

Role of m1 receptor-G protein coupling in cell proliferation in the prostate.

Luthin GR; Wang P; Zhou H; Dhanasekaran D; Ruggieri MR
Allegheny University, Department of Physiology and Biophysics, Philadelphia, PA 19102, USA.
Life Sci (England) 1997, 60 (13-14) p963-8

The prostate gland from several animal species contains variable levels of muscarinic subtypes, but only the human prostate expresses significant levels of the m1 subtype. We studied muscarinic receptor activity in human benign prostatic hypertrophy (BPH) as well as several cell lines derived from prostate cancer. The BPH we studied expresses approximately 75% of the m1 receptor and undetectable levels of the other receptor subtypes whereas PC3 cells express only the m3 receptor subtype. DU145 and LnCaP cells express approximately equal levels of m1 and m3 receptor subtypes. Only the PC3 cells responded to carbachol with an increase in turnover of polyphosphoinositides, and none of the cell lines responded with effects on cAMP metabolism. Co-precipitation of receptors with heterotrimeric guanine nucleotide-binding regulatory proteins demonstrated interactions of the m1 receptors with Gi, Gq and G16 in BPH tissue and of the m1 and m3 receptors with Gi, Gq and G12 in PC3 and DU145 cells. Mitogen activated protein kinase (ERK) activity was seen in response to carbachol in PC3 and DU145 but not LnCaP cells. Finally, carbachol promoted cell proliferation in all three cell lines. Thus, there appears to be no consistent relationship between ERK activity, cell proliferation, and the subtype mediating the proliferative response, amongst these prostate cancer cell lines.

Transurethral prostatectomy--new trends.

Churchill JA
Northern Kentucky University, Highland Heights, USA.
Geriatr Nurs (United States) Mar-Apr 1997, 18 (2) p78-80

Treatment for benign prostatic hypertrophy has changed drastically within the past 3 years. Two new procedures-visual laser ablation of the prostate and transurethral electrovaporization prostatectomy, as well as improvements in the transurethral prostatectomy-have resulted in decreased recovery time and early discharge. Postoperative nursing observations for the visual laser ablation of the prostate and transurethral electrovaporization prostatectomy are quite different than for the transurethral prostatectomy. Discharge teaching has become extremely important because patients are now being discharged within 24 hours and most often with a Foley catheter. Patient response to the new procedures has been positive even though there are some disadvantages. (10 Refs.)

[Sabal serrulata extract in the management of symptoms of prostatic hypertrophy]

Kondas J; Philipp V; Dioszeghy G
Fovarosi Onkormanyzat Peterfy Sandor utcai Korhaz-Rendelointezet, Urologiai-sebeszeti Osztaly, Budapest.
Orv Hetil (Hungary) Feb 16 1997, 138 (7) p419-21

The effectiveness of Sabal serrulata (dwarf palm) extract was evaluated in the treatment of 38 patients with symptomatic prostatic hyperplasia. During a 12-month treatment controlled by investigations the subjective symptoms decreased in nearly three fourth of the patients. Side effects were not observed. According to uroflowmetric investigations the average peak flow value increased from 10.36 ml/sec to 14.44 ml/sec (p < 0.0001) and the average mean flow value from 0.02 ml/sec to 7.45 ml/sec (p < 0.001). After treatment residual urine volume decreased or was nil in more than 9/10 of the cases. The average decrease of residue was 47 ml (p < 0.001). The average decrease in prostatic volume was 10.6% (p < 0.02). On the basis of their favorable experience the authors recommend the administration of Sabal serrulata extract in the treatment of patients with mild or moderate symptoms of prostatic hyperplasia.

[Comparative effects of transurethral incision (TUIP) and the combination of TUIP and LHRH agonists in the treatment of benign prostatic hypertrophy]

Di Silverio F; D'Eramo G; Flammia GP; De Vico A; Casale P; Sciarra A
Service d'Urologie U. Bracci, Universite La Sapienza, V. Le Policlino, Rome, Italie.
J Urol (Paris) (France) 1996, 102 (3) p111-6

Between December 1991 and December 1993, 74 BPH patients with an increased operative risk and concomitant diseases such as diabetes mellitus and hypertension were submitted to a transurethral incision of the prostate (TUIP). After TUIP, patients were randomized to two different groups: group 1 was followed without additional treatment and group 2 received an LHRH analogue for the first 6 months of follow-up. With respect to transurethral resection of the prostate (TURP), TUIP has been shown to demonstrate a lower perioperative morbidity. This advantage has lent further support to this technique as a valid alternative for patients in poor general conditions who are at high risk with more invasive procedures. One of the limits of TUIP is the long-term effectiveness. Aim of this study was to ascertain whether in patients with BPH and an increased operative risk who require immediate and definitive treatment but with a low perioperative morbidity, the long-term effectiveness of TUIP can be stabilized by the administration of an LHRH analogue. At present postoperative follow-up ranges from a minimum of 24 months to a maximum 48 months (mean 38.4 months). Perioperative morbidity rate associated with TUIP was 8.1%. In the group randomized to combination therapy (TUIP + LHRH analogue), the clinical condition of the patients was not modified by LHRH analogue treatment and none of the patients withdrew from treatment. Loss of sexual potency occurred in all patients on LHRH analogue, however, none of these patients discontinued treatment for this reason. At the end of the cycle of hormone treatment, sexual potency returned to pretreatment values in 69.5% of patients after a mean of 3.2 months. In this study the objective efficacy of the treatment was evaluated using flow rate measurements, and the subjective assessment of outcomes, using the International Prostate Symptom Score. Statistically significant differences between the two groups (TUIP alone or TUIP + LHRH analogue) (p < 0.01) were reported at 6 months and were still maintained at 24 months of follow up. Results emerging from this investigation confirm that TUIP may be considered extremely safe procedure with low operative risk. In selected BPH patients who are at high risk, with a more invasive procedure and who must be submitted to immediate and definitive treatment, the association of an LHRH analogue seems to increase the long-term effectiveness of TUIP. Five year follow-up studies are still in progress.

Immunochemical detection of 5 alpha-reductase in human serum.

Lombardo ME; Hudson PB
Urology Section/Surgical Service, Department of Veterans Affairs Medical Center, Bay Pines, Florida 33504, USA.
Steroids (United States) Nov 1996, 61 (11) p651-6

This study represents a continuing effort to find a new biomarker for the diagnosis and management of prostatic cancer. Polyclonal antibodies were prepared to a peptide (CAKP) representing amino acids 28 to 43 of the 5 alpha-reductase type 2 isozyme. Using immunoaffinity-purified antibodies, the sera of 62 patients were examined by Western blot following polyacrylamide gel electrophoresis. A positive band was detected in the sera of several patients at 42 kDa compatible with the purified native glycosylated 5 alpha-reductase type 2. These bands were nullified on coincubation of the antibody with the CAKP peptide. Analysis by high-performance liquid chromatography and amino acid sequencing by N-terminal Edman degradation of the immunoaffinity-purified antigen to the antipeptide antibodies of a patient with adenocarcinoma of the prostate suggests that the 5 alpha-reductase type 2 isozyme may be linked to an immunoglobulin. An identical immunoaffinity-purified antigen to the CAKP peptide was isolated from a section of prostatic tissue from a different patient showing benign prostatic hypertrophy with severe dysplasia. It is suggested that an immunological response to the 5 alpha-reductase type 2 isozyme was elicited in both instances.

Nd:YAG laser transurethral evaporation of the prostate (TUEP) for urinary retention.

Fournier GR Jr; Tewari A; Induhara R; Gajenderan V; Narayan P
Department of Veterans Affairs, Division of Urology, San Francisco, California 94121, USA.
Lasers Surg Med (United States) 1996, 19 (4) p480-6

BACKGROUND AND OBJECTIVE: Little information is available regarding the effectiveness of laser prostatectomy in patients with urinary retention from benign prostatic hyperplasia since there is no paper specifically dealing with laser prostatectomy in patients in urinary retention.

STUDY DESIGN/MATERIALS AND METHODS: Twenty two unselected consecutive patients presenting with urinary retention due to benign prostatic hypertrophy underwent transurethral evaporation of the prostate (TUEP) using a neodymium:YAG laser and total internally reflecting side-firing free beam quartz fiber. All patients failed at least one voiding trial and averaged > 30 days of urinary catheter drainage preoperatively. A contact evaporation technique was used to evaporate a "TURP-like" channel in the prostatic fossa by means of a series of parallel evaporation troughs.

RESULTS: Eighteen of 22 patients completed 6 months of follow up. Two patients were lost to follow up and two failed TUEP. The average AUA score dropped from 26 to 9 at 1 month and to 3.4 by 6 months postoperatively. All patients who successfully underwent TUEP were urinating spontaneously by 10 days. Average time to catheter removal was 3.5 days. Maximal uroflow was 15.7 ml/sec at 1 month and 20.3 ml/sec by 6 months. Postvoid residual preoperatively averaged 784 ml and decreased to 76 ml by 1 month. Pre- and postoperative hematocrit and serum sodium values did not vary by more than 5%.

CONCLUSION: From this preliminary series we conclude that aggressive evaporation of prostatic tissue is feasible endoscopically and provides a reliable method of near bloodless removal of tissue.

Possible mechanisms of action of transurethral needle ablation of the prostate on benign prostatic hyperplasia symptoms: a neurohistochemical study

Zlotta AR; Raviv G; Peny MO; Noel JC; Haot J; Schulman CC
Department of Urology, Erasme University Hospital, Brussels, Belgium.
J Urol (United States) Mar 1997, 157 (3) p894-9

PURPOSE: Transurethral needle ablation of benign prostatic hypertrophy (BPH) is a rapid, anesthesia-free outpatient procedure using low level radiofrequency energy that produces coagulative necrosis lesions at temperatures of approximately 100C. Clinically, significant improvement in objective and subjective parameters has been observed in BPH patients. Transurethral needle ablation has also been shown to be effective in relieving urinary retention. However, the precise mechanism of action of this procedure remains to be clarified. Ablation could produce its action on the dynamic component of the infravesical outlet obstruction. We analyzed the possible effects of transurethral needle ablation on the intraprostatic innervation.

MATERIALS AND METHODS: Histological sections from 10 open prostatectomy specimens (BPH) recovered 1 to 46 days after transurethral needle ablation were stained with hematoxylin and eosin and an immunohistochemical technique, using antibodies against S100 proteins and nonspecific enolase as specific nerve markers, and against anti-prostate specific antigen and anti-desmin for glandular and muscle cells, respectively. We used 5 BPH specimens as controls.

RESULTS: Microscopic examination of the treated areas showed necrotic lesions affecting epithelial and smooth muscle cells in the transition zone at a depth of 0.3 to 1.0 cm, from the preserved urethra. Nerve fibers in the control specimens and untreated prostatic areas were predominant in the urethral submucosal layer and in the stroma surrounding the epithelial nodules. No staining of any axon or isolated nerve cell was observed in any specimen treated by transurethral needle ablation, and there was a sharp and clear delineation between treated and untreated areas.

CONCLUSIONS: Our study demonstrated severe thermal damage to intraprostatic nerve fibers caused by transurethral needle ablation. A long-term denervation of alpha-receptors and/or sensory nerves could explain the clinical effects of transurethral needle ablation of the prostate. Theoretically, the best location to produce necrotic lesions should include submucosal and subcapsular nerve endings. Differences in the distribution of the adrenoreceptors and morphometry of the prostate transition zone could partly explain differences in clinical outcome observed after transurethral needle ablation of the prostate.

Histopathologic evaluation of the canine prostate following electrovaporization

Benjamin DS; Oberg KC; Saukel GW; Ruckle HC; Stewart SC
Loma Linda University School of Medicine, Department of Urology, California, USA.
J Urol (United States) Mar 1997, 157 (3) p1144-8

PURPOSE: Transurethral electrovaporization of the prostate (TVP) for symptomatic benign prostatic hypertrophy (BPH) has proven to be efficacious with minimal patient morbidity. When compared to transurethral resection of the prostate (TURP), TVP demonstrates comparable postoperative flow rates, American Urologic Association (AUA) symptom score indices, and a potential cost savings. However, in the human studies it has not been possible to correlate these clinical parameters with procedure-related histopathologic changes in the prostate immediately postoperative or during wound healing. The following study was done using a canine model in an effort to evaluate these histopathologic changes.

METHODS AND MATERIALS: Fifteen hounds (25-35 kg.) underwent antegrade electrovaporization of the prostate, via an open cystotomy, using a Circon ACMI USA series resectoscope and video equipment. The dogs were sacrificed and the prostates harvested at various intervals postoperatively (0-11 weeks). The prostates were evaluated grossly as well as histologically for cavitary defects, depth of necrosis, and cellular response.

RESULTS: Prostates examined immediately following the procedure demonstrated superficial necrosis (less than 2 mm.) in the region of vaporized tissue. One week postoperatively, the vaporized regions demonstrated an intense acute inflammation amidst superficial necrosis with focal hemorrhage and dystrophic calcification. Transient glandular cystic changes developed, but were resolving by seven weeks postoperatively. Re-epithelialization was underway by the third postoperative week and epithelial stratification underway by the fifth week. There was no extension of the initial two millimeter zone of necrosis at any time point examined.

CONCLUSION: TVP in the canine model vaporizes prostatic tissue at the site of contact. Only a shallow remnant of necrosis remains at the site of vaporization, indicating the highly localized effect of this technique. Healing at the site of vaporization occurs in a rapid and expected manner. These data provide a histopathologic rationale for the minimal morbidity and the efficacious nature of this technique demonstrated in clinical studies.

Transurethral vaporization of the prostate: a promising new technique.

Thomas KJ; Cornaby AJ; Hammadeh M; Philp T; Matthews PN
Department of Urology, University Hospital of Wales, Cardiff, UK.
Br J Urol (England) Feb 1997, 79 (2) p186-9

OBJECTIVE: To evaluate the efficacy and safety of transurethral electrovaporization of the prostate (TUVP), using a grooved roller electrode, for the surgical treatment of symptomatic benign prostatic hypertrophy (BPH).

PATIENTS AND METHODS: TUVP was carried out using a grooved roller electrode, pure-cutting diathermy and a standard irrigating resectoscope to rapidly heat prostatic tissue to > 100 degrees C, resulting in vaporization and cavitation of the prostatic adenoma. Over a 10 month period, 116 patients (mean age 69.8 years, range 51-93) with symptomatic BPH (confirmed by a symptom score, urinary flow rate and an ultrasonographic estimate of residual volume) were treated by TUVP. Patients with carcinoma of the prostate, an elevated level of prostate-specific antigen or those in chronic urinary retention were excluded from the study. Each patient was followed up every 4 months during the first post-operative year, assessing their flow rate, residual volume and symptom score.

RESULTS: Symptom scores improved by 67% and residual volumes by 72%; the mean maximal flow rate increased from 8.5 mL/s (range 3.5-14) before treatment to 20.5 mL/s (range 4.5-39.0) at the same 4 month review. The procedure was simple and safe, with a mean operative duration of 35 min (range 20-65), and no patients required a blood transfusion. Most patients had their catheters removed within 24 h and were discharged on the second day after treatment.

CONCLUSION: The effectiveness of TUVP in improving symptoms and flow rates in patients with BPH was established. With minimal capital expenditure and a reduced in-patient stay. TUVP appears to have several advantages over other surgical treatments for BPH, although continued follow-up is needed to establish the long-term results.

Early experience with high-intensity focused ultrasound for the treatment of benign prostatic hypertrophy.

Sullivan LD; McLoughlin MG; Goldenberg LG; Gleave ME; Marich KW
Department of Surgery, Vancouver Hospital.
Br J Urol (England) Feb 1997, 79 (2) p172-6

OBJECTIVE: To evaluate the safety and effectiveness of high-intensity focused ultrasound (HIFU) in patients with benign prostatic hypertrophy (BPH).

PATIENTS AND METHODS: The study comprised 25 patients (mean age 67 years: range 47-84) with BPH treated using the Sonoblate HIFU device. Patients were evaluated before and after one treatment of HIFU using the American Urological Association (AUA) symptom score, peak urinary flow rate (Qmax) and a quality-of-life (QOL) score, and any complications were noted.

RESULTS: Five patients with large glands were withdrawn because the failure rate was high in these patients. The remaining 20 patients showed a mean improvements in the AUA symptom score (20.25 to 9.56), Qmax (9.2 to 13.7 mL/s) and QOL score (4.75 to 2.50). There were no major complications.

CONCLUSIONS: HIFU is safe, produces minimal side-effects or complications and relieves the symptoms of prostatism.

Detection of bladder tumor by urine cytology in cases of prostatic hypertrophy.

Rammou-Kinia R; Anagnostopoulou I
Department of Cytology, Tzanio General Hospital, Piraeus, Greece.
Diagn Cytopathol (United States) Dec 1996, 15 (5) p409-11

Routine urine cytology has been performed for 809 male patients presenting with symptoms due to prostatic hypertrophy. In 6.42% of the cases, bladder tumor was revealed incidentally diagnosed by urine cytology. Cystoscopy and bladder biopsies were performed to confirm malignancy. The age of these patients ranged from 48-84 years (mean 65.2) and they complained mainly of irritative bladder symptoms. It is therefore strongly indicated that all patients with prostatic disease should have routine cytological examination of urine sediments.

Quantification and distribution of alpha 1-adrenoceptor subtype mRNAs in human prostate: comparison of benign hypertrophied tissue and non-hypertrophied tissue.

Nasu K; Moriyama N; Kawabe K; Tsujimoto G; Murai M; Tanaka T; Yano J
Molecular Biology Department, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Br J Pharmacol (England) Nov 1996, 119 (5) p797-803

1. There are at least three alpha 1-adrenoceptor subtypes, alpha 1a, alpha 1b and alpha 1d, in human tissues. Using an RNase protection assay, we have now determined the amount of each subtype mRNA in human prostatic tissue, for both benign prostatic hypertrophy (BPH) and non-BPH. In all tissue samples examined, the predominant subtype mRNA was alpha 1a. The total abundance of alpha 1-adrenoceptor mRNA in BPH samples was over six times that in non-BPH samples. This increase was mostly accounted for by alpha 1a, which was almost nine times as abundant in BPH samples as in non-BPH samples. The abundance of alpha 1b was almost the same between BPH and non-BPH samples, and the abundance of alpha 1d in BPH samples was about three times that in non-BPH samples. The ratio of the numbers of the subtype mRNAs, alpha 1a: alpha 1b: alpha 1d, was 85:1:14 in BPH samples and 63:6:31 in non-BPH samples.

2. In situ hybridization studies showed no significant differences in the tissue localization of alpha 1-adrenoceptor subtype mRNAs between BPH and non-BPH samples. alpha 1a and alpha 1d were clearly detected in the interstitium of the prostate, where alpha 1a was stained more intensely than alpha 1d, and the positive sites were primarily smooth muscle cells. In contrast, alpha 1b staining was very faint.

3. This increase in mRNA abundance may be directly related to the contraction of prostatic tissue that leads to obstruction of the urinary tract in BPH patients. Specifically, our data suggest that increased expression of the alpha 1a subtype may be primarily responsible for the contraction of the prostate.

Prostate-specific antigen and age. Is there a correlation? And why does it seem to vary?

Kirollos MM
Urology Department, South Devon Health Care Trust, Torquay, UK.
Eur Urol (Switzerland) 1996, 30 (3) p296-300

OBJECTIVES: To determine whether there is a significant correlation between age and prostate-specific antigen (PSA) and to explain the wide literature variations in its value.

METHODS: Two different groups were studied; the first (n = 403) consisted of patients undergoing prostatectomies for symptomatic benign prostatic hypertrophy (BPH) and the second (n = 192) of patients with no evidence of prostate cancer who required no treatment.

RESULTS: The correlation coefficient found in the surgical group was low (0.09) and was statistically insignificant while in the second group it was much higher (0.36) and had a high statistical significance (p < 0.001). This reflected the age difference between the two groups rather than the difference in clinical characteristics as proved by the gradual decrease in the value of the coefficient by the gradual exclusion of the younger age groups. The correlation became statistically insignificant for those older than 60 years.

CONCLUSIONS: It is concluded that the correlation between age and PSA is a variable one showing a gradual decline in its coefficient with the gradual increase in the age of the population studied. This implies a relatively orderly rise in PSA with age up to a limit of 60 years. Beyond this age, the relationship between age and PSA becomes disorderly. This pattern of relationship can easily be explained by the known rate of growth of BPH and would explain the literature variations.

Colocalization of immunoglobulin binding factor and prostate specific antigen in human prostate gland.

Maegawa M; Kamada M; Maeda N; Aono T; Izumi K; Kagawa S; Koide SS
Department of Obstetrics and Gynecology, School of Medicine, University of Tokushima, Japan.
Arch Androl (United States) Nov-Dec 1996, 37 (3) p149-54

Immunoglobulin binding factor (IgBF) produced in the prostate is a useful marker for the diagnosis of prostatic tumor. IgBF was localized in the majority of epithelial cells of benign prostatic hypertrophy by an immunohistochemical technique. Prostate specific antigen (PSA), a known marker for prostatic cancer, was localized to all epithelial cells. Double immunolabeling of IgBF and PSA using fluorescent methods revealed that all epithelial cells producing IgBF were also immunopositive for PSA and some cells were positive only for PSA. The present findings suggest that the prostatic glands consist of two types of epithelial cells, one producing both IgBF and PSA and the other producing PSA alone.

A study of the efficacy and safety of transurethral needle ablation (TUNA) treatment for benign prostatic hyperplasia.

Millard RJ; Harewood LM; Tamaddon K
New South Wales University, Sydney, Australia.
Neurourol Urodyn (United States) 1996, 15 (6) p619-28

The objective of this early phase III study was to determine the efficacy and safety of transurethral needle ablation (TUNA) in patients presenting in acute urinary retention due to benign prostatic hyperplasia (BPH). Between September 1993 and August 1994, 20 patients of mean age 68.8 years were entered into a two-center study and treated with TUNA after presenting in acute urinary retention and having failed at least one trial of voiding. A mean of 5.4 lesions at shield temperatures of 54.6 degrees C were produced. Patients were reviewed at 1, 3, 6, and 12 months (mean, 6.2 months). In 17 of 20 patients, voiding was reestablished in a mean of 2.6 days. Three patients required TURP for persistent retention, and 2 patients had delayed TURP for bothersome symptoms. Two voiders died later of unrelated causes. Five patients were lost to follow-up at 6 months but were voiding when last reviewed. Symptom scores decreased from a mean of 19.0 (range 4-35) to 8.25 (range 1-20) at 12 months (p = 0.06). Mean peak flow rate was 11.4 ml/sec (range 6.6-16.8) at 12 months (p = 0.001). Mean prostatic volume at baseline was 65.8 cc and decreased to 56 cc at 12 months (p = 0.111). The treatment was well tolerated by all patients, and side effects were mild, including urinary tract infection and epididymo-orchitis. This study demonstrates the safety and effectiveness of TUNA procedure in patients with urinary retention due to benign prostatic hypertrophy.

Continued on the next page...

Alpha 1a-adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy.

Shibata K; Hirasawa A; Moriyama N; Kawabe K; Ogawa S; Tsujimoto G
Department of Molecular, Cell Pharmacology, National Children's Medical Research Center, Tokyo, Japan.
Br J Pharmacol (England) Jul 1996, 118 (6) p1403-8

1. Two restriction fragment length polymorphisms of the human alpha 1a-adrenoceptor gene digested with PstI restriction enzyme exist; the nucleotide change causes the substitution of C residue for T at nucleotide 1441, thereby Arg492 to Cys492 transition, which might confer an additional putative palmitoylation site in the carboxy-terminal segment of the alpha 1a-adrenoceptor. In the present study, we compared their pharmacological properties and examined whether this alpha 1a-adrenoceptor polymorphism is associated with benign prostatic hypertrophy (BPH).

2. The frequency of alpha 1a-adrenoceptor polymorphism was not differently distributed between patients with benign prostatic hypertrophy (BPH) and normal subjects in Japan; thus, the relative frequencies of the C and T alleles were 0.90 : 0.10 in normal male subjects (n = 45) and 0.87 : 0.13 in BPH patients (n = 222), respectively. However, the frequency distribution of this polymorphism was significantly different between the Japanese and U.S. populations; thus, C and T alleles were 0.34 and 0.66 in U.S. populations.

3. Utilizing Chinese hamster ovary (CHO) cells stably expressing the two polymorphic alpha 1a-adrenoceptors (Arg492 and Cys492), we compared their binding affinity and signal transduction. Radioligand binding studies with 2-[beta-(4-hydroxy-3[125I]-iodophenyl) ethylamino-methyl]tetralone ([125I]- HEAT) showed no marked difference in the antagonist or agonist binding affinities between the two receptors. Also, both receptors were found to be coupled to the calcium signaling, and the concentration-cytosolic Ca2+ concentrations ([Ca2+]i) response relationships for noradrenaline were similar for the two polymorphic receptors. Furthermore, the receptor-mediated [Ca2+]i response was markedly desensitized after a 2 h exposure of phenylephrine (10 microM), and the extent of the desensitization was not significantly different between the two receptors.

4. In summary, the results showed that the two alpha 1a-adrenoceptors generated by genetic polymorphism have similar pharmacological characteristics, and the receptor-mediated [Ca2+]i response can be desensitized in a similar manner. The study did not provide any evidence to support the hypothesis that alpha 1a-adrenoceptor gene polymorphism is associated with BPH.

[Double-blind evaluation of mepartricin 150.000 U (40 mg) compared with placebo in benign prostatic hypertrophy]

Prezioso D; Mirone V; Fabrizio F; Lotti T
Cattedra di Urologia, II Facolta di Medicina, Universita degli Studi, Napoli.
Minerva Urol Nefrol (Italy) Dec 1996, 48 (4) p207-11

The therapeutic efficacy and tolerance of a new 150,000 U (40 mg) formulation of mepartricin (to be administered once-a-day in the evening) were evaluated during a double-blind study against placebo in 2 groups of uncomplicated BPH patients treated for 60 days. The data obtained disclosed a positive pharmaco-therapeutic effect of this new formulation coupled with excellent local and systemic tolerance. At the end of trial the various objective and subjective parameters considered showed marked improvement in the group treated with mepartricin, with statistically significant differences from the placebo-treated group. The treatment efficacy was judged positive in 74-78% of cases by patients and physicians in the mepartricin group and in 36.4% of cases in the placebo group.

[Alternative treatment of benign prostatic hypertrophy]

Fiorelli C; Menghetti I; Razmjouei K; Macchiarella A; Celso M
Clinica Urologica I, Universita degli Studi, Firenze.
Minerva Urol Nefrol (Italy) Dec 1996, 48 (4) p177-82

In our study we propose to find an alternative to surgery management of IPB usable in DH regime with current instrumentation or with new technology from physics. We retrospectively reviewed techniques commonly mentioned in the literature to value benefits about cost, comfort, outcomes, and, at the same time, we stress disadvantages regarding each of these. TUI is economical, can be done in a few minutes, involves minimum bleeding, but can't be utilized in III lobe prostate and it doesn't provide material for histological tests. TUBT, feasible with light patient sedation, provides not satisfying results. Hyperthermia is necessary in selected cases. TULIP must be effected in anesthesia, needs complicated and expensive instrumentation, and it isn't practicable in III lobe prostate. Urethral stent application is expensive and not satisfactory in large size and III lobe prostate. The outcomes we obtained with TUI are similar to TUR; TUBT obtains good symptomatological results only in 20% of cases at 12 months. Hyperthermia and TULIP obtain an improvement in urinary flow rate from 20 to 60% and 50% respectively. Stent application provides good results. We think that the most modern, effective and economical alternative to the surgery of prostate adenoma is endoscopic surgery in TUI model. (19 Refs.)

Transition zone ratio and prostate-specific antigen density: the index of response of benign prostatic hypertrophy to an alpha blocker.

Kurita Y; Ushiyama T; Suzuki K; Fujita K; Kawabe K
Department of Urology, Hamamatsu University School of Medicine, Japan.
Int J Urol (Japan) Sep 1996, 3 (5) p361-6

BACKGROUND: The aim of the present study was to determine whether the indices of transrectal ultrasonography (TRUS) are related to the clinical response to tamsulosin, a long-acting selective alpha 1-blocker.

METHODS: Sixty patients with symptomatic benign prostatic hypertrophy (BPH) were treated with tamsulosin hydrochloride (0.2 mg/day) for 2 months. The findings on TRUS and uroflowmetry and the AUA symptom score before treatment were compared with those obtained at the end of the 2 month treatment period. For the indices of TRUS, transition zone (TZ) volume, transition zone ratio (TZ ratio = TZ volume/total prostate volume), total prostate volume, and prostate specific antigen density (PSAD) were calculated.

RESULTS: There was a significant correlation between the pretreatment TZ ratio and the residual urine volume (r = 0.421, P = 0.0005). Patients with a lower TZ ratio and/or PSAD responded well to the treatment. The correlation between the PSAD value and the percent change in peak urinary flow rate was statistically significant (r = -0.432, P = 0.0009).

CONCLUSION: TRUS provides simple parameters of PSAD that can be used to predict the response of patients to tamsulosin hydrochloride.

[A case of prostate cancer diagnosed one and half year after retropubic prostatectomy for benign prostatic hypertrophy]

Kato Y; Nakata S; Sato J; Mayuzumi T; Shimizu T
Department of Urology, Gunma Cancer Center.
Hinyokika Kiyo (Japan) Nov 1996, 42 (11) p907-9

A 77-year-old male patient underwent retropubic prostatectomy for benign prostatic hypertrophy. Fourteen months after operation, a hard nodule was palpated on the left lobe on digital examination. Transrectal needle biopsy was performed, and the pathological diagnosis was poorly differentiated adenocarcinoma of the prostate. It was one and half year after prostatectomy that we diagnosed prostate cancer (stage D2). (8 Refs.)

The use of alpha-adrenoceptor antagonists in the pharmacological management of benign prostatic hypertrophy: an overview.

Hieble JP; Ruffolo RR Jr
SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
Pharmacol Res (England) Mar 1996, 33 (3) p145-60

Benign prostatic hypertrophy (BPH) produces symptomatic urethral obstruction in a significant percentage of older men. Since the incidence of BPH is age related, the clinical and economic impact of this disease will continue to progress as average lifespan increases. BPH is associated with growth of both glandular and stromal elements of the prostate gland. Glandular hyperplasia can be partially reversed by withdrawal of androgenic tone with androgen receptor antagonists or steroid-5-alpha-reductase inhibitors. However, the reduction in prostatic size produced by these agents has little effect on the dynamic tone induced by nerve mediated contraction of stromal smooth muscle. This tone is mediated by activation of alpha-adrenoceptors. Therefore the alpha-adrenoceptor antagonists represent a useful pharmacological approach to the treatment of BPH. Studies in isolated strips of human prostate show that either exogenous alpha-adrenoceptor agonists or electrical field stimulation will induce contraction. Studies with selective antagonists such as prazosin show that this response is mediated by the alpha 1-adrenoceptor, even though radioligand binding studies show the presence of alpha 1 and alpha 2 adrenoceptor subtypes in approximately equal density. Following the cloning of multiple alpha 1-adrenoceptors, the contractile response in human prostate has been assigned to the alpha 1A adrenoceptor. However, recent data would suggest a functional role for another subtype, which has not yet been cloned, and designated as alpha 1L based on a relatively low affinity for prazosin. Clinical trials have shown efficacy of a variety of alpha-adrenoceptor antagonists in BPH, including non-selective agents such as phenoxybenzamine, as well as a variety of selective alpha 1-adrenoceptor antagonists, most structurally related to prazosin. The agents most commonly employed at the present time include the prazosin analogs terazosin, doxazosin and alfuzosin, as well as the structurally unrelated indoramin and tamsulosin. The design of new alpha 1-antagonists for BPH has concentrated on agents producing preferential blockage of urogenital vis-a-vis vascular alpha 1-adrenoceptors, based either on selectivity for the alpha 1A-adrenoceptor subtype or on functional uroselectivity in animal models. While these newer agents offer the prospect of reducing the incidence of the cardiovascular side effects associated with current therapy their superiority over nonselective alpha 1-adrenoceptor antagonists remains to be demonstrated in the clinical setting. (158 Refs.)

Clinical application of basic arginine amidase in human male urine.

Matsuda Y; Miyashita A; Fujimoto Y; Umeda T; Akihama S
Department of Biochemistry, Meiji College of Pharmacy, Tokyo, Japan.
Biol Pharm Bull (Japan) Aug 1996, 19 (8) p1083-5

Basic human urinary arginine amidase (or esterase, called BHUAE) which is only found in male urine, was measured from normal volunteers between the age of 4 and 70 years using D-valyl-L-leucyl-L-arginine-p-nitroanilide as a substrate. BHUAE increases during early adolescence, between 8 to 17 years of age. Then, BHUAE decreases in the twenties and takes a certain range of value in the mature age group, between the late thirties and fifties. In patients with prostate cancer, a significant increase in BHUAE was demonstrated in comparison with the healthy male group (control) over 55 years old. On the other hand, patients with benign prostatic hypertrophy showed no significant elevation of this enzyme activity. It would appear that the measurement of BHUAE in urine can be used as a marker of prostate cancer in an advanced age group.

Free to total prostate-specific antigen (PSA) ratio is superior to total-PSA in differentiating benign prostate hypertrophy from prostate cancer.

Van Cangh PJ; De Nayer P; Sauvage P; Tombal B; Elsen M; Lorge F; Opsomer R; Wese FX
Department of Urology, Saint Luc University Hospital, Brussels, Belgium.
Prostate Suppl (United States) 1996, 7 p30-4

BACKGROUND: Serum prostate-specific antigen (PSA) exists in different molecular forms, and their respective concentration has been proposed as a useful tool to improve discrimination between benign prostatic hypertrophy (BPH) and prostate cancer (PC).

METHODS: The relevance of the free to total PSA ratio was prospectively studied in a selected urology clinic population of 420 patients. Total serum PSA ranged from 2.1 to 30 ng/ml; 154 had PC and 266 had BPH.

RESULTS: Receiver operating characteristic (ROC) curves were constructed for the total population (total-PSA range from 2.1 to 30 ng/ml) and for the diagnostic gray zone of 2.1-10 ng/ml. For the two groups, the free to total PSA ratio had a higher specificity than total-PSA for all sensitivity levels. Cut-off values were found to, vary with prostate weight.

CONCLUSIONS: Although free to total PSA ratio demonstrated better performances than total-PSA, its use in screening appears problematic, due to the low prevalence of prostate cancer.

Clinical study on estramustine binding protein (EMBP) in human prostate.

Shiina H; Igawa M; Ishibe T
Department of Urology, Shimane Medical University, Izumo, Japan.
Prostate (United States) Sep 1996, 29 (3) p169-76

To elucidate the characteristics of estramustine binding protein (EMBP) in human prostate, tissue EMBP concentration was examined in 42 benign prostatic hypertrophy (BPH), 34 untreated prostatic carcinoma (PC), 8 hormone refractory PC (hr-PC), as well as 13 control prostate human tissue samples by RIA using rat-EMBP antibody, and the concentration thus obtained was compared with dihydrotestosterone (DHT), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), and zinc, indices exhibiting androgen dependency in the prostate. EMBP concentration correlated significantly with DHT and PSA levels in the control prostate and BPH, but not in untreated PC. In BPH, EMBP concentration increased significantly after administration of fluoxymesterone (4 mg/day for 2 weeks), whereas it decreased significantly after estramustine phosphate (280 mg/day for 2 weeks). The EMBP/DHT ratio in moderately and poorly differentiated, and the hr-PC was significantly higher than in controls, BPH, and well-differentiated PC. In addition, untreated PC with an EMBP/DHT ratio of more than 40 showed significantly lower progression-free probability as compared with PC with an EMBP/DHT of less than 40. These results suggest that (1) EMBP in BPH and well-differentiated PC preserves androgen dependency, but not in moderately and poorly differentiated, nor in hr-PCs, indicating that EMBP is a protein different from PAP and PSA, and (2) that the tissue EMBP/DHT ratio might be useful as a marker for predicting disease progression.

Three-year followup of patients treated with lower energy microwave thermotherapy.

de Wildt MJ; D'Ancona FC; Hubregtse M; Carter SS; Debruyne FM; de la Rosette JJ
Department of Urology, Nijmegen University Hospital, The Netherlands.
J Urol (United States) Dec 1996, 156 (6) p1959-63

PURPOSE: A retrospective study was done to investigate the long-term outcome of patients treated with lower energy transurethral microwave thermotherapy.

MATERIALS AND METHODS: A total of 305 patients with lower urinary tract symptoms and benign prostatic hypertrophy underwent transurethral microwave thermotherapy according to a similar protocol at 2 centers.

RESULTS: After 3 years of followup 133 patients who had undergone transurethral microwave thermotherapy alone were available for study. During this observation period significant symptomatic improvement from baseline and an improved maximum flow rate of 2.6 ml. per second were noted. Of the patients 125 underwent invasive or medical treatment.

CONCLUSIONS: After 3 years of followup lower energy transurethral microwave thermotherapy showed significant and durable improvements in baseline parameters in 52% of the patients.

Detection of Chlamydia trachomatis in the prostate by in-situhybridization and by transmission electron microscopy.

Corradi G; Bucsek M; Panovics J; Verebelyi A; Kardos M; Kadar A; Frang D
Semmelweis University of Medicine, Budapest, Hungary.
Int J Androl (England) Apr 1996, 19 (2) p109-12

Chlamydia trachomatis infection has been investigated in the prostate gland using in-situ DNA hybridization and transmission electron microscopy. Sixty-four samples of tissue removed by trans-urethral resection or by open surgery from men with benign prostatic hypertrophy (BPH), were examined histologically and 20 of the cases were found to be positive for mononuclear cell infiltration. Some samples were then investigated using in-situ hybridization and transmission electron microscopy. Out of 20 tissue samples with mononuclear cell infiltration, nine were found to be positive for C. trachomatis infection.

Breast and prostate cancer in the relatives of men with prostate cancer.

McCahy PJ; Harris CA; Neal DE
Department of Surgery, University of Newcastle upon Tyne, UK.
Br J Urol (England) Oct 1996, 78 (4) p552-6

OBJECTIVE: To assess the risk of breast, ovarian and prostate cancer in the families of men with prostate cancer.

PATIENTS AND METHODS: A case-control study was performed by interviewing patients with prostate cancer and obtaining detailed information on family histories of cancer. Controls were hospital-based patients, of a similar age to the cases, with bladder cancer or benign prostatic hypertrophy.

RESULTS: A total of 209 cases and 322 controls were interviewed; of the cases, 22.5% had family members with a history of one or more of breast, ovarian or prostate cancers, compared with 15.2% of controls (P < 0.05). The odds ratio (OR) of having prostate cancer when there was a positive family history was 8.22 and the OR of a female relative of a patient with prostate cancer having breast cancer was 1.51. There was no apparent increased risk of ovarian or any other cancer.

CONCLUSIONS: We confirm previous reports of an increased incidence of prostate cancer in the families of men with prostate cancer and report a similarly increased incidence of breast cancer in female relatives. We suggest that detailed family histories be taken routinely and intend to analyse blood samples provided from this study for genetic abnormalities.

Effect of finasteride on free and total serum prostate-specific antigen in men with benign prostatic hyperplasia.

Matzkin H; Barak M; Braf Z
Department of Urology, Tel-Aviv University, Israel.
Br J Urol (England) Sep 1996, 78 (3) p405-8

OBJECTIVE: To examine changes in the free-to-total (f/t) serum prostate-specific antigen (PSA) ratio among men treated with finasteride for benign prostatic hypertrophy.

PATIENTS AND METHODS: Blood samples were taken from 20 men (mean age 71 years, range 61-87) before and after a minimum of 9 months of treatment with finasteride and the f/tPSA ratio determined using the Immulite assay system.

RESULTS: Although mean total and free PSA levels decreased significantly, the mean f/tPSA ratio increased only slightly and not significantly; the ratios remained unchanged in men with an initially low or high (< > 10%) ratio.

CONCLUSIONS: Concern has been expressed over the loss of the discriminatory power of serum PSA in a patient receiving treatment with finasteride. The f/tPSA ratio, currently used to help differentiate benign from malignant processes in the prostate, remains valid during treatment with finasteride; it does not affect the f/tPSA ratio.

The safety of finasteride used in benign prostatic hypertrophy: a non-interventional observational cohort study in 14,772 patients.

Wilton L; Pearce G; Edet E; Freemantle S; Stephens MD; Mann RD
Drug Safety Research Unit, Southampton, UK.
Br J Urol (England) Sep 1996, 78 (3) p379-84

OBJECTIVE: To examine the safety of finasteride as used in general medical practice to treat benign prostatic hypertrophy (BPH).

PATIENTS AND METHODS: Information was collected on 14,772 patients who were included in an observational cohort study conducted using Prescription-Event Monitoring.

RESULTS: Finasteride was reported to have been effective in 60% of the patients in whom an opinion on efficacy was recorded. Impotence or ejaculatory failure was reported in 2.1% of the patients, decreased libido in 1% and gynaecomastia and related conditions in 0.4%. Impotence was the most frequent reason for stopping treatment with finasteride and was the most commonly reported adverse reaction to the drug. Of the patients included in the elderly cohort involved in this study, 819 (5.5%) died; none of these deaths was attributed to finasteride.

CONCLUSION: Impotence or ejaculatory failure, decreased libido and gynaecomastia in a small proportion of patients were associated with the use of finasteride. The results of this study strongly suggest that this drug is acceptably safe when used in accordance with the current prescribing information.

[Transurethral thermotherapy with microwaves in patients with benign prostatic hypertrophy and urinary retention: comparative study between high energy (25) and standard energy (2.0)]

Mompo Sanchis JA; Paya Navarro JJ; Prosper Rovira F
Centro Medico Urotecno, Clinica Casa de Salud, Valencia, Espana.
Arch Esp Urol (Spain) May 1996, 49 (4) p337-46

OBJECTIVES: During a 36-month period, 63 patients with benign prostatic hypertrophy (BPH) who presented urinary retention, were treated on an outpatient basis by transurethral microwave thermotherapy (TUMT) with the Prostatron device using analgosedation.

METHODS: Treatment consisted of a single one hour session with Prostasoft 2.0 for the first group of 11 patients. The second group of 19 patients received 2 hours Prostasoft 2.0. The third group comprised of 33 patients were treated with higher energy TUMT (Prostasoft 2.5/1 h 30 min). The number of sessions (144) depended on prostate length: L < 45 mm: one session (Prostanec catheter); L < 55 mm: two sessions (additional black catheter session); L < 65 mm: three sessions (additional white catheter session).

RESULTS: In the first group of patients, 54% were catheter-free after one year (5 TURP); 84% (3 TURP) in the second group; 96% (1 TURP) in the third group. The morbidity was similar for all groups.

CONCLUSIONS: Only high energy TUMT (Prostasoft 2.5/1 h 30 min) appears to be a minimally reasonable alternative to surgery in elderly patients with urinary retention secondary to prostatism and concomitant diseases. Longer followup is warranted to determine if the beneficial effects will persist.

Detection of alpha 1-adrenoceptor subtypes in human hypertrophied prostate by insituhybridization.

Moriyama N; Kurimoto S; Horie S; Nasu K; Tanaka T; Yano K; Hirano H; Tsujimoto G; Kawabe K
Department of Urology, Faculty of Medicine, University of Tokyo, Japan.
Histochem J (England) Apr 1996, 28 (4) p283-8

Adrenergic stimulation induces contraction of hypertrophied prostatic tissue via the alpha 1 adrenoceptor, and the results of pharmacological studies suggested the existence of adrenoceptor subtypes. Recently three subtypes (alpha 1a, alpha 1b, and alpha 1d) were cloned. Using probes for these subtypes, we demonstrated their expression in the tissues of ten cases of benign prostatic hypertrophy, using in situ hybridization. To determine the ratio between these subtypes, an RNase protection assay was also performed in three cases. Expression of the alpha 1a and alpha 1d adrenoceptors was diffuse in the smooth muscles of the interstitium, but was absent in glandular epithelial cells. On the contrary, the alpha 1b adrenoceptor was hardly detectable. The RNase protection assay confirmed the absence of the alpha 1b adrenoceptor, the ratio of alpha 1a and alpha 1d being 4:1. These results supported the idea that the differences in prostatic contractile response to several adrenergic drugs are based on the affinities of these drugs for the different subtypes.

Safety profile of 3 months' therapy with alfuzosin in 13,389 patients suffering from benign prostatic hypertrophy.

Lukacs B; Blondin P; MacCarthy C; Du Boys B; Grippon P; Lassale C
Service Urologie, Hopital Tenon, Paris, France.
Eur Urol (Switzerland) 1996, 29 (1) p29-35

The safety profile of alfuzosin, a selective alpha 1-adrenergic antagonist, was assessed in a total of 13,389 patients (mean age 66.9 +/- 8.5 years) with symptomatic benign prostatic hypertrophy in two open, noncontrolled, multicentre, post-marketing surveillance studies, both conducted in France. Alfuzosin was prescribed at the recommended dose of 2.5 mg t.i.d., according to the current labelling recommendations, for a 3-month period. Clinical safety was assessed using spontaneous reporting of adverse events leading to discontinuation of treatment. Overall, 89.7% of the patients completed the treatment period. Drop outs were recorded in 10.3% of patients: 3.7% for intolerance; 1.5% for resolution of urinary symptoms; 2.1% for lack of efficacy, and 3.0% for loss to follow-up, noncompliance, and miscellaneous reasons. Two thirds of the adverse events leading to discontinuation were vasodilatory and occurred in 2.7% of the patients: vertigo/dizziness (1.4%); malaise (0.6%); hypotension (0.4%), and headache (0.4%). Other adverse events (predominantly gastrointestinal disorders) were recorded in < 1.2% of the patients. Three quarters of the adverse events occurred during the first week of therapy. As expected, adverse events were more frequent in the elderly (aged over 75 years) and in patients taking cardiovascular drugs or with concomitant cardiovascular disease. Overall, alfuzosin was very well tolerated and the adverse event profile was consistent with the cumulative experience of the drug. No unexpected or serious adverse events considered to be related to alfuzosin were recorded. Particular care must be taken when prescribing for very elderly patients and/or those with concomitant cardiovascular disease for which they are receiving therapy.

Estramustine-binding protein in carcinoma and benign hyperplasia of the human prostate.

Shiina H; Urakami S; Shirakawa H; Igawa M; Ishibe T; Usui T
Department of Urology, Shimane Medical University, Izumo, Japan.
Eur Urol (Switzerland) 1996, 29 (1) p106-10

For the purpose of elucidating whether the biological characteristics of estramustine-binding protein (EMBP) are different in benign prostatic hypertrophy (BPH) and prostatic carcinoma (PC) and also to determine the clinical value of EMBP in the tissue, the EMBP concentration in 19 patients with BPH and 26 with untreated PC was measured by means of radioimmunoassay (RIA) using an antibody raised against EMBP obtained from the rat ventral prostate and compared simultaneously with the dihydrotestosterone (DHT) level in the same tissue. The level of serum prostate-specific antigen (PSA) was also measured in these patients. The EMBP concentration was significantly correlated with the tissue DHT level in BPH and well-differentiated PC (r = 0.745, p < 0.0001), whereas it did not correlate in moderately and poorly differentiated PC (r = -0.159, p = 0.542). By comparing well-differentiated PC with moderately and poorly differentiated PC, the EMBP concentration was significantly lower in the former than in the latter two conditions (p < 0.005) in spite of the highest tissue DHT level in well-differentiated PC. The ratio of the EMBP concentration to the DHT level in moderately and poorly differentiated PC was significantly higher when compared with that observed in either BPH or well-differentiated PC (p < 0.005, respectively). However, the level of serum PSA did not reflect the histological differentiation of PC. These results suggest that: (i) the correlation of the EMBP concentration to the DHT level changed with the progression of the histological grade, and (ii) the ratio of the EMBP concentration to the DHT level in the tissue is clinically valuable in elucidating the biological potential of individual tumors.

Surface-epitope masking and expression cloning identifies the human prostate carcinoma tumor antigen gene PCTA-1 a member of the galectin gene family.

Su ZZ; Lin J; Shen R; Fisher PE; Goldstein NI; Fisher PB
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Proc Natl Acad Sci U S A (United States) Jul 9 1996, 93 (14) p7252-7

The selective production of monoclonal antibodies (mAbs) reacting with defined cell surface-expressed molecules is now readily accomplished with an immunological subtraction approach, surface-epitope masking (SEM). Using SEM, prostate carcinoma (Pro 1.5) mAbs have been developed that react with tumor-associated antigens expressed on human prostate cancer cell lines and patient-derived carcinomas. Screening a human LNCaP prostate cancer cDNA expression library with the Pro 1.5 mAb identifies a gene, prostate carcinoma tumor antigen-1 (PCTA-1). PCTA-1 encodes a secreted protein of approximately 35 kDa that shares approximately 40% sequence homology with the N-amino terminal region of members of the S-type galactose-binding lectin (galectin) gene family. Specific galectins are found on the surface of human and marine neoplastic cells and have been implicated in tumorigenesis and metastasis. Primer pairs within the 3' untranslated region of PCTA-1 and reverse transcription-PCR demonstrate selective expression of PCTA-1 by prostate carcinomas versus normal prostate and benign prostatic hypertrophy. These findings document the use of the SEM procedure for generating mAbs reacting with tumor-associated antigens expressed on human prostate cancers. The SEM-derived mAbs have been used for expression cloning the gene encoding this human tumor antigen. The approaches described in this paper, SEM combined with expression cloning, should prove of wide utility for developing immunological reagents specific for and identifying genes relevant to human cancer.

[The significance of free-type PSA and complex-type PSA in patients with prostatic carcinoma--the characteristics of ACS-PSA method compared with that of Delfia- and Eiken-PSA method]

Arai K; Honda M; Hosoya Y; Sumi S; Umeda H; Yoshida K
Department of Urology, Dokkyo University School of Medicine, Tochigi, Japan.
Rinsho Byori (Japan) Apr 1996, 44 (4) p345-50

We studied the clinical significance of free-type prostate specific antigen (PSA) and bound-type PSA in serum of the patients with prostatic carcinoma and benign prostatic hypertrophy. The levels of PSA, gamma-seminoprotein and prostatic acid phosphatase (PAP) in 17 healthy adult males, 20 patients with benign prostatic hypertrophy and 23 patients with prostatic carcinoma were measured by ACS-PSA, Delfia and Eiken-PSA method. The levels of PSA in serum from prostatic carcinoma patients was significantly elevated as compared with that from benign prostatic hypertrophy. Linear regression analysis of the data showed that, although overall correlations were well, different assays gave different PSA concentrations. We have studied the forms of PSA in serum by gel filtration technique and measured PSA levels in each fractions using three methods. Moreover, the characteristics of ACS-PSA method was compared with that of Delfia and Eiken-PSA method. Two peaks of PSA were detected on the elution profiles from three prostatic carcinoma patients sera. Those were estimated complex-type PSA (90kDa) and free-type PSA (30kDa). The complex-type PSA fractions detected by ACS-PSA method were almost identical with that detected by Delfia-PSA method, while free-type PSA fractions detected by ACS-PSA method were greater quantity than those by Delfia and Eiken method. Many factors were contributory to the difference between the assay kits on serum complex-type PSA and free-type PSA levels. The present results suggest that there are some quantitative differences in the immunorecognition of complex-type PSA and free-type PSA between the assay kits.

The Oxford Laser Prostate Trial: a double-blind randomized controlled trial of contact vaporization of the prostate against transurethral resection; preliminary results.

Keoghane SR; Cranston DW; Lawrence KC; Doll HA; Fellows GJ; Smith JC
Department of Urology, Churchill Hospital, University of Oxford, UK.
Br J Urol (England) Mar 1996, 77 (3) p382-5

OBJECTIVE: To compare the results of contact laser vaporization and transurethral resection of the prostate (TURP) in a double-blind randomized controlled clinical trial.

PATIENTS AND METHODS: The study comprised 148 patients with clinical benign prostatic hypertrophy (BPH) who were recruited and allocated randomly to undergo either TURP (72 patients) or laser ablation of the prostate (76 patients). The outcome was assessed using the American Urological Association (AUA -7) symptom score after 1 and 3 months as the primary measure and by urinary flow rates, haematological factors and the duration of hospital stay and length of catheterization.

RESULTS: With 90% statistical power, the results at 3 months showed no clinical or statistical difference between the treatments in change in AUA symptom score. A lower blood loss, hospital stay and duration of catheterization significantly favoured the laser treatment, although the failure rate of trial without catheter and the rate of re-operation were higher after laser treatment.

CONCLUSIONS: These early data are encouraging for this technique, although the outcome after one year requires evaluation before advocating the widespread uptake of this method.

A case-control study of cancer of the prostate in Somerset and east Devon.

Ewings P; Bowie C
Somerset Health Authority, Taunton, UK.
Br J Cancer (England) Aug 1996, 74 (4) p661-6

A case-control study in Somerset and east Devon was undertaken to investigate possible risk factors for prostatic cancer. A total of 159 cases, diagnosed at Taunton. Yeovil and Exeter hospitals between May 1989 and May 1991, were identified prospectively and interviewed with a structured questionnaire. A total of 161 men diagnosed with benign prostatic hypertrophy and 164 non-urological hospital controls were given identical questionnaires. The questionnaire covered a wide range of factors identified from previous studies, but the central hypotheses for this study related to diet (fat and green vegetables), sexual activity and farming as an occupation. This study found no association between farming and risk of prostatic cancer (odds ratio = 0.74, 95% confidence interval 0.46-1.18), nor with sexual activity as measured by number of sexual partners (chi-squared test for trend P = 0.52). A history of sexually transmitted disease was not significantly associated with prostatic cancer, but the numbers involved were very small and the odds ratio of 2.06 (0.38-11.2) is consistent with the hypothesis. A range of questions aimed at eliciting dietary fat intake produced no significant associations, although meat consumption showed increasing risk with increasing consumption (test for trend P = 0.005). Increased consumption of leafy green vegetables was associated with lower risk, but not significantly so (test for trend P = 0.16). As expected with so many factors investigated, some statistically significant associations were found, although these can only be viewed as hypothesis generating in this context. These included apparent protective effects of circumcision and high fish consumption.

Usefulness of PSA density and PSA excess in the differential diagnosis between prostate cancer and benign prostatic hypertrophy.

Diaz F; Morell M; Rojo G
Urology Department, Carlos Haya Regional Hospital, Malaga, Spain.
Int J Biol Markers (Italy) Jan-Mar 1996, 11 (1) p12-7

The usefulness of PSA density (PSAD) was evaluated in relation to the volume of the transitional zone (PSAT) and PSA excess. With this purpose we conducted a study including 27 patients diagnosed as having prostatic cancer (PC) and 46 patients with benign prostatic hypertrophy (BPH). In all of them, the PSA concentration in the serum was determined as well as the total prostatic volume and the transitional zone volume; digital rectal examination (DRE) was also performed. The major diagnostic efficacy was obtained with the excess of PSA (73%, cutoff = -13 ng/ml), followed by DRE (68%), PSAT (64%, cutoff = 0.5), PSAD (64%, cutoff = 0.2), and lastly PSA and ultrasonography (60%). Multivariate analysis (logistic regression) demonstrated PSA excess and DRE to be the best predictors. The model obtained by regression shows the best positive predictive value, and PSA excess the best negative predictive value. Consequently, PSA excess could be relevant in prostate cancer diagnosis.

[Detection of prostate cancer in urological practice: clinical establishment of serum PSA reference values by age]

Yamazaki H; Suzuki Y; Madarame A; Katoh N; Masuda F; Ohishi; Endo K
Department of Urology, Jikei Daisan Hospital, Tokyo, Japan.
Nippon Hinyokika Gakkai Zasshi (Japan) Mar 1996, 87 (3) p702-9

BACKGROUND: Determinations of serum levels of prostate specific antigen (PSA) are widely used for the detection of prostate cancer, but have not demonstrated sufficient sensitivity and specificity to be useful in urological practice. In order to enhance the diagnostic value of serum PSA, we studied the distribution of serum PSA levels by age in urological patients without clinical evidence of prostate cancer and determined clinical PSA reference values by age decades.

METHODS: The study included a total of 590 male patients aged 40 to 89 years who visited our urological clinic complaining of voiding symptoms from January 1991 to October 1994, but had no clinically evident prostate cancer. We defined patients to be without clinical evidence of prostate cancer if they had negative test results in digital rectal examination, ultrasonography, and serum PSA assay, or had positive test results in one or more of these tests but had a nonmalignant prostate biopsy. Serum PSA levels were measured by E-Test Tosoh II (AIA-PACK PA, normal range; 0 to 5.3 ng/ml). The patients were grouped by age decades and serum PSA values were given as percentiles.

RESULTS: Analyzed by Pearson's correlation coefficient, serum PSA levels were correlated significantly with patient age (r = 0.24, p < 0.001). Prostatic volume was correlated weakly but significantly with patient age (r = 0.12, p = 0.005), and PSA density was also correlated significantly with patient age (r = 0.20, p < 0.001). Thus, serum PSA levels were demonstrated to increase with advancing patient age. Factors other than benign prostatic hypertrophy were also suggested to explain the increase in serum PSA levels in older patients. With the 95th percentile for serum PSA as the upper limit, the clinical PSA reference values by age decades were determined to be 2.6 ng/ml for patients aged 40 to 49 years, 5.0 ng/ml for 50 to 59 years, 7.5 ng/ml for 60 to 69 years, 10.1 ng/ml for 70 to 79 years, and 12.4 ng/ml for 80 to 89 years.

CONCLUSION: We found a significant increase in serum PSA levels with advancing patient age. Thus, it is appropriate to have serum PSA reference values by age decades. Prospective clinical trials are necessary to define the usefulness of the PSA reference values by patient age in urological practice.

Free-to-total prostate specific antigen ratio as a single test for detection of significant stage T1c prostate cancer.

Elgamal AA; Cornillie FJ; Van Poppel HP; Van de Voorde WM; McCabe R; Baert LV
Department of Urology, University Hospitals of KU Leuven, Belgium.
J Urol (United States) Sep 1996, 156 (3) p1042-7; discussion 1047-9

PURPOSE: We investigated whether impalpable, invisible (stage T1c) but significant prostate cancer can be detected better by determining the free-to-total prostate specific antigen (PSA) ratio of equivocal PSA serum levels.

MATERIALS AND METHODS: The specificity of free-to-total PSA ratio using research monoclonal enzyme immunoassays was compared to that of PSA greater than 4.0 ng./ml. in 117 consecutive patients with PSA 3 to 15 ng./ml. (Hybritech Tandem-R assay) due to untreated benign prostatic hypertrophy or prostate cancer. Of the patients 77% underwent adenectomy or radical prostatectomy with thorough pathological evaluation of surgical specimens.

RESULTS: Benign prostatic hypertrophy had a greater median free-to-total PSA ratio than stages T1c and T2 or greater prostate cancer (0.16 versus 0.09 and 0.11 ng./ml., p = 0.0001 and p = 0.0268, respectively). In stage T1c prostate cancer, areas under receiver operating characteristic curves were 0.58 and 0.84 for PSA and free-to-toal PSA ratio, and free-to-total PSA ratio correlated with prostate volume (r = 0.49, p = 0.005) and Gleason score (r = -0.37, p = 0.036). Pathologically, 84% of stage T1c cancers were significant and comparable to stage T2 or greater cancers.

CONCLUSIONS: Free-to-total PSA ratio enhances the efficacy of PSA measurement by improving specificity for detecting impalpable, invisible but significant stage T1c prostate cancer.

[Transurethral thermotherapy with microwaves in symptomatic prostatic benign hypertrophy: comparison between the high-energy (2.5) protocol and the standard protocol (2.0)]

Mompo Sanchis JA; Paya Navarro JJ; Prosper Rovira F
Centro Medico Urotecno, Clinica Casa de Salud, Valencia, Espana.
Arch Esp Urol (Spain) Mar 1996, 49 (2) p99-109

OBJECTIVES: The efficacy of three therapeutic protocols of transurethral microwave thermotherapy (TUMT), was compared in a study comprised of 355 patients that had been treated for benign prostatic hypertrophy (BPH) between March, 1992 and March, 1995.

METHODS: TUMT were performed with the Prostatron device with intravenous analgosedation and on an outpatient basis. In the first group (Protocol A), 122 patients received a standard treatment (Prostasoft 2.0/hour); the second group of 81 patients were included into Protocol B (Prostasoft 2.0/2 hours); 152 patients were treated with higher-energy in Protocol C (Prostasoft 2.5/1 hour). The number of sessions (635) performed were based on prostatic length: L < 45 mm - one session (Prostanec catheter); L < 55 mm - two sessions (additional black catheter session); L < 65 mm - three session (additional white catheter session).

RESULTS: All groups improved significantly for subjective symptoms (symptom score) and objective parameters (peak flow, residual urine). Comparison of the results between the three groups at 6 and 12 months showed a significantly better clinical outcome in protocol C >> B > A: Morbidity was higher in group C than in group B than in group A.

CONCLUSION: Our results indicate that transurethral microwave thermotherapy is a safe and effective procedure which improves objective and subjective parameters. Better outcomes were obtained with long session times (2H) and overall higher energy (2.5) input, which may be explained by the creation by cavities within the prostate, but at the cost of increased morbidity. However, TUMT can still be delivered as an anesthesia-free and outpatient non-surgical alternative treatment for BPH.

Two-dimensional outcome analysis as a guide for quality assurance of prostatectomy.

Cohen YC; Olmer L; Mozes B
Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Int J Qual Health Care (England) Feb 1996, 8 (1) p67-73

PURPOSE: To find outlier centers in different aspects of quality of care by comparing two different outcomes and adjusting to case mix in benign prostatic hypertrophy (BPH) patients undergoing prostatectomy.

MATERIALS AND METHODS: An observational study including 537 consecutive patients undergoing prostatectomy for BPH in three medical centers in Israel between 1991 and 1992. Data were collected from medical charts and by a structured interview. Outcomes examined included immediate surgical complications and postoperative symptom effect level. Regression analysis was employed to adjust for case mix and to determine the additional contribution of medical centers.

RESULTS: We found significant variability among centers in crude symptom effect, but not after case mix adjustment. An outlier was detected in both the crude and case mix-adjusted urological complications.

CONCLUSIONS: Centers may differ with various outcomes. This may reflect variability in different levels of performance within different aspects of the process of care in prostatectomy procedures.

Alpha blockers: a reassessment of their role in therapy.

Cauffield JS; Gums JG; Curry RW Jr
University of Florida College of Medicine, Gainesville, USA.
Am Fam Physician (United States) Jul 1996, 54 (1) p263-6

Intended for the treatment of hypertension, alpha blockers offer advantages in treating patients who also have other risk factors for coronary artery disease. Alpha blockers lower blood pressure by decreasing vascular resistance and are effective for the treatment of mild to moderate hypertension. In addition, alpha blockers have beneficial effects on lipid levels; they increase high-density lipoprotein levels and decrease total cholesterol, low-density lipoprotein and triglyceride levels. Alpha blockers do not induce glucose intolerance or hyperinsulinemia. Although they appear to decrease left ventricular mass, the clinical significance of this action is unknown. Alpha blockers are also effective for improving the symptoms of benign prostatic hypertrophy, although surgery is recommended for patients with severe symptoms. (22 Refs.)

Effect of prostatic growth factor, basic fibroblast growth factor, epidermal growth factor, and steroids on the proliferation of human fetal prostatic fibroblasts.

Luo D; Lin Y; Liu X; Qin Z; Zhao C; Zhang Y; Yu Z
Department of Biochemistry, Shandong Medical University, Jinan, People's Republic of China.
Prostate (United States) Jun 1996, 28 (6) p352-8

To study the relationship between androgen metabolism and the pathogenesis of benign prostatic hypertrophy, we purified a growth factor from benign hyperplastic tissue of human prostates and assayed the proliferative responses of human fetal prostatic fibroblasts to the purified growth factor (hPGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), dihydrotestosterone (DHT), and estradiol (E2). Prostatic tissue extracts were fractionated using heparin-Sepharose chromatography. The fraction that eluted with 1.3-1.7 M NaCl contained the majority of mitogenic activity. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS/PAGE) of the lyophilyzed active fraction showed a band at 17,000 daltons. Human prostatic fibroblasts were isolated from fetal prostate and tested for their proliferative responses to hPGF, bFGF, EGF, DHT, and E2. hPGF, as well as bFGF and EGF, did increase tritiated thymidine incorporation into the cultured fibroblasts. DHT(10(-7) M) had a significant stimulatory effect on cell growth in serum-free media after 6 days of culture. E2(10-7 M) had no effect on cell proliferation. The combination of DHT and E2 showed no synergistic effect. We conclude that our purified hPGF, bFGF, and EGF promote cell growth directly, DHT indirectly, while E2 does not. The effect of DHT appears to be mediated via the increased production and/or secretion of growth factor(s). Possibly, the bFGF-like hPGF purified from human benign hyperplastic prostatic tissue is such a mediator.

The impact of prostate-specific antigen density in predicting prostate cancer when serum prostate-specific antigen levels are less than 10 ng/ml.

Akdas A; Tarcan T; Turkeri L; Cevik I; Biren T; Ilker Y
Department of Urology, Marmara University School of Medicine, Istanbul, Turkey.
Eur Urol (Switzerland) 1996, 29 (2) p189-92

OBJECTIVE: To evaluate the impact of prostate-specific antigen density (PSAD) when serum levels of prostate-specific antigen (PSA) are less than 10 ng/ml.

METHODS: We retrospectively analyzed 134 patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsies according to Cooner's algorithm.

RESULTS: Histopathological examination revealed prostate cancer (PCa) in 22 (16%) and benign prostatic hypertrophy (BPH) in 112 (84%) patients. Five patients (23%) with PCa had PSAD < 0.15 of whom 3 had PSA < 4 ng/ml and 2 had PSA between 4 and 10 ng/ml. In the BPH group, 60 patients (54%) had PSAD below 0.15 whereas 52 patients (46%) had PSAD over 0.15. With 0.15 as the cutoff level of PSAD, the sensitivity and specificity of PSAD was found as 77 and 54%, respectively. In this patient population, PSA with the cutoff level of 4 ng/ml has sensitivity and specificity levels of 77 and 33%, respectively. According to these results, a statistically significant difference was found between PSA and PSAD only in terms of diagnostic specificity (chi-square, p < 0.05). There were 29 patients with negative digital rectal examination (DRE) and TRUS and PSA 4-10 ng/ml who underwent biopsy because of PSAD > 0.15. No cancer was detected in this group of patients, suggesting that biopsy in this subgroup may be unnecessary.

CONCLUSION: Although PSAD seemed to increase the specificity without any decrease in sensitivity in the diagnosis of prostate cancer, it did not bring any practical advantage in our selected population since all PCa cases had abnormal DRE and/or TRUS findings.

Usefulness of prostate-specific antigen density as a diagnostic test of prostate cancer.

Filella X; Alcover J; Molina R; Carrere W; Carretero P; Ballesta AM
Department of Clinical Biochemistry, (Unit Cancer Research), Hospital Clinic i Provincial, Barcelona, Spain.
Tumour Biol (Switzerland) 1996, 17 (1) p20-6

To evaluate the diagnostic usefulness of prostate-specific antigen density (PSAD) in prostate cancer (PC) prostate-specific antigen (PSA) concentrations were measured in 175 patients with benign prostatic hypertrophy (BPH) and 50 patients with PC. Patients with BPH were classified according to the presence of complications of the disease: urinary infection or the presence of a bladder catheter. PSAD levels were observed to be greater than 0.15 in 3% of the patients with uncomplicated BPH and in 40% of the patients with complicated BPH. PSA levels were higher than 10 micrograms/l in 3 and 27% of these patients, respectively. High levels of PSAD were observed in 80% of the patients with cancer. Sixty-four percent of the patients with cancer presented PSA levels greater than 10 micrograms/l. These results indicate that PSAD is a useful parameter in the differential diagnosis of PC and BPH with the diagnostic efficacy of PSAD being greater than that of the serum determination of PSA..