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PubMed1990

Serum acid phosphatase in patients with localised prostatic cancer, benign prostatic hyperplasia or normal prostates.

Serum acid phosphatase levels were determined in 247 men with surgically confirmed intracapsular prostatic cancer (30 patients), benign prostatic hyperplasia (BPH) (114 patients) or palpably normal prostates (103 men). Both radioimmunoassay (245 cases) and an enzymatic method (218 cases) were used. Using radioimmunoassay, the mean serum prostatic acid phosphatase (PAP) level was significantly higher in patients with BPH than in patients with intracapsular cancer or men with normal prostates. The weight of hyperplastic tissue removed during operation in the BPH group correlated closely with PAP concentrations. Age or the presence (or absence) of an indwelling catheter had no effect on PAP concentration. Using the enzymatic method, the highest levels of acid phosphatase were also detected in patients with BPH but the difference was less marked. It was concluded that intracapsular cancer does not elevate serum acid phosphatase levels as determined by radioimmunoassay or an enzymatic method. BPH alone leads to significant rises in PAP concentrations. The degree of BPH correlates with PAP levels.

Acid Phosphatase↗
PubMed2001

Association of vitamin D receptor and 17 hydroxylase gene polymorphisms with benign prostatic hyperplasia and benign prostatic enlargement.

OBJECTIVES: To determine whether polymorphisms in 17 hydroxylase (CYP17) and vitamin D receptor (VDR) genes have an association to prostate volume/histology and endocrine patterns in elderly men with lower urinary tract symptoms (LUTS). METHODS: Elderly men with LUTS underwent the following investigations: International Prostate Symptom Score (IPSS), uroflowmetry, serum prostate-specific antigen (PSA) assessment of prostate volume, and an endocrine study. Polymorphisms of CYP17 (T-->C substitution in the 5' promoter region) and VDR (T1055C) genes were detected by polymerase chain reaction followed by restriction-length polymorphism analysis, using DNA from peripheral white blood cells. Clinical and endocrine parameters and the prostate stroma/epithelial ratio were correlated to CYP17 and VDR genotypes. RESULTS: A total of 148 (mean +/- SD, 67.0 +/- 9.7 years) patients were analyzed. IPSS (17.8 +/- 7.0), prostate volume (41.9 +/- 17.9 cc), maximum flow rate (10.9 +/- 5.8 mL/s), and PSA (4.7 +/- 4.7 ng/mL) indicate a typical LUTS population. Mean endocrine levels were consistently within age-specific reference values. Neither CYP17 nor VDR gene polymorphisms revealed an association to prostate size, PSA, clinical parameters, and endocrine parameters. Men who had the A1/A1 CYP17 genotype had on average a greater stromal/epithelial ratio than men with the A1/A2 or A2/A2 genotypes, yet after adjusting for multiple testing, this significance disappeared. CONCLUSIONS: Gene polymorphisms of CYP17 and VDR have no association to prostate volume, clinical parameters, and endocrine parameters in elderly men. The association of CYP17 polymorphism and prostate histology warrants further studies. Assessment of gene polymorphisms might provide new insights into the pathogenesis of benign prostatic hyperplasia and benign prostate enlargement and may hold promise as genetic biomarkers of this disease.

Aged↗
PubMed1979

Comparison of spontaneous and experimentally induced canine prostatic hyperplasia.

Spontaneous prostatic hyperplasia in the beagle appears to progress with age from a glandular to a cystic histological appearance. Prostatic hyperplasia can be induced in young beagles with intact testes by treatment for 4 mo with either dihydrotestosterone or 5 alpha-androstane-3 alpha, 17 beta-diol, alone, or with either of these steroids in combination with 17 beta-estradiol. In contrast, the induction of prostatic hyperplasia in young castrated beagles, in which the gland had been allowed to involute for 1 mo, requires the administration of both 17 beta-estradiol and either 5 alpha-androstane-3 alpha, 17 beta-diol or dihydrotestosterone. Testosterone and 17 beta-estradiol, either singly or in combination, did not produce the hyperplastic condition in intact or castrated beagles. The experimentally induced prostatic hyperplasia is identical in pathology to the glandular hyperplasia that occurs naturally in the aging dog with intact testes. However, cystic hyperplasia was not produced by any of the treatments tested in young animals.

Androstane-3,17-diol↗
PubMed2004

[Role of apoptosis and chronic prostatitis in the pathogenesis of benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is the most common hyperplastic disease in aging male. The prostatic hyperplasia results from imbalance of immunoneuroendocrine homeostasis in which a paracrine activity of growth factors plays a substantial role. The mechanisms of BPH are multifactorial and are not yet recognized in the all details. Cell growth in the normal prostate is regulated by a delicate balance between cell death and cell proliferation. Disruption of the molecular mechanisms that regulate these processes may underline the abnormal growth of the prostate. On the basis of literature we have reviewed the role of endocrine environment, growth factors, intracellular proteins, pharmacological agents, microelements and particular role of the chronic prostatitis in the development of benign prostatic hyperplasia.

Apoptosis↗
PubMed1995

Citrate as an in vivo marker to discriminate prostate cancer from benign prostatic hyperplasia and normal prostate peripheral zone: detection via localized proton spectroscopy.

OBJECTIVES: This study was designed to determine whether citrate levels detected by localized 1H spectroscopy could reliably discriminate regions of prostate adenocarcinoma from surrounding regions of normal peripheral zone and benign prostatic hyperplasia (BPH). METHODS: In 28 patients and 5 volunteers stimulated echo proton spectroscopy was used in conjunction with endorectal surface coils to obtain water-suppressed 1H spectra from regions of normal prostate peripheral zone, BPH, and prostate cancer. 1H spectra from prostate cancer patients were correlated with pathologic areas identified on T2-weighted endorectal coil magnetic resonance (MR) images and histologic study of the step-sectioned gland after surgery. RESULTS: The major finding of in vivo studies was consistently lower citrate levels in prostate cancer compared with BPH and normal prostate peripheral zone. This was reflected by significantly (P < 0.05) lower mean citrate/(creatine plus choline) peak area ratio observed for regions of cancer (0.67 +/- 0.17) compared with BPH (1.21 +/- 0.29) and normal peripheral zone (1.46 +/- 0.28). Moreover, there was no overlap of individual cancer and normal peripheral zone citrate ratios and no significant difference between citrate ratios in regions of normal peripheral zone in young volunteers (1.28 +/- 0.14) and age-matched patients (1.46 +/- 0.28). The observed alterations in vivo citrate levels were supported by citrate concentration data obtained from extracts of histologically proven samples of normal, benign, and malignant prostatic tissues removed at surgery. In vitro citrate levels in the normal peripheral zone (30.9 +/- 8.5 mumol/g wet weight) and BPH (46.3 +/- 5.4 mumol/g wet weight) were significantly higher than those for prostate cancer (3.74 +/- 0.54 mumol/g wet weight). CONCLUSIONS: These studies further demonstrate the potential of citrate as an in vivo marker for discriminating prostate cancer from surrounding regions of normal peripheral zone and BPH.

Adenocarcinoma↗
PubMed1983

Androgens and estrogens: their interaction with stroma and epithelium of human benign prostatic hyperplasia and normal prostate.

Growth and integrity of human prostatic epithelium is strongly dependent upon the adjacent stroma. Furthermore, the human prostate is under the control of sex hormones. Both facts prompted us to compare epithelium with stroma of human benign prostatic hyperplasia (BPH) and normal prostate (NPR) concerning their metabolism, binding and tissue concentrations of androgens and estrogens. In vitro metabolism was analyzed by t.l.c., androgen and estrogen binding sites were determined by a charcoal adsorption technique, androgen and estrogen tissue concentrations were measured by RIA. The main results are--(1) Metabolism: BPH stroma shows 2-3 times higher 5 alpha-reductase activity than epithelium. This high 5 alpha-reductase activity in BPH stroma dictates the differences between unseparated BPH and NPR, in the former the 5 alpha-reductase activity being 2 times higher. The 3 alpha(beta)-hydroxysteroid dehydrogenase (HSDH) activity is more evenly distributed between stroma and epithelium of BPH and NPR. The ratios of 5 alpha-reductase to HSDH activity in the various tissue fractions indicate that the highest enzymatically regulated 5 alpha-dihydrotestosterone (DHT) enrichment must occur in BPH stroma. (2) Tissue concentrations: unseparated BPH contains 2.2 times more DHT than NPR. About 70% of the total DHT content is found in nuclear fractions, whereby the nuclear DHT content of BPH stroma is significantly higher than that of BPH epithelium. In addition, nuclei of BPH stroma contain significantly more estradiol than epithelial nuclei. (3) Binding: the androgen receptor is evenly distributed between epithelium and stroma of BPH, while the estrogen receptor is preferably assayed in BPH stroma. These studies indicate that the BPH stroma is not only a preferential tissue for 5 alpha-reductase activity and DHT enrichment but also for nuclear estradiol accumulation.

3-Hydroxysteroid Dehydrogenases↗
PubMed2005

Benign prostatic hyperplasia (BPH) and prostatitis: prevalence of painful ejaculation in men with clinical BPH.

OBJECTIVES: To determine the prevalence and importance of pain/discomfort on ejaculation (prostatitis-like symptom) in men with lower urinary tract symptoms (LUTS) diagnosed with clinical benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Baseline data from 5096 men reporting LUTS suggestive of BPH, and enrolled in the ALF-ONE study by general practitioners and urologists in Europe, Asia, Latin America, the Middle East and Canada, were analysed to determine the prevalence and significance of pain/discomfort on ejaculation. All the men were asked to complete the International Prostate Symptom Score (IPSS) questionnaire, the bother score (IPSS question 8), and the Danish Prostate Symptom Score sexual-function questionnaire (DAN-PSSsex) which assesses three symptoms (rigidity of erection, amount of ejaculate and pain/discomfort on ejaculation) and their bothersomeness. RESULTS: There were 3700 sexually active men who had an evaluable answer to the DAN-PSSsex question related to pain/discomfort on ejaculation. Of these, 688 (18.6%) reported pain/discomfort on ejaculation and 609 (88%) considered it was a problem. Patients with painful ejaculation had more severe LUTS and reported greater bother (P < 0.001). Of men with painful ejaculation, 72% reported erectile dysfunction, of whom 91% considered it a problem, and 75% reported reduced ejaculation, of whom 81% considered it a problem. By contrast, of men with no ejaculatory discomfort, 57% reported erectile dysfunction, of whom 79% considered it a problem, and 56% reported reduced ejaculation, of whom 57% considered it a problem. A history of urinary tract infection was reported by 12% of men in the ejaculatory pain group, compared with 7% in the LUTS-only group, while 5% of men in the ejaculatory pain group reported macroscopic haematuria, compared to 3% in the LUTS-only group. Men with ejaculatory pain were slightly younger, but there were no significant differences in duration of LUTS, history of acute urinary retention, prostate-specific antigen concentrations or maximum urinary flow rate compared to the LUTS-only group. CONCLUSIONS: Of sexually active men with LUTS suggestive of BPH, approximately 20% complain of specific prostatitis-like symptoms of pain/discomfort on ejaculation, and these men clearly differ from those who present with LUTS only. For most the symptom is a significant bother. Men with BPH and painful ejaculation have more severe LUTS and reported greater bother, and had a higher prevalence of erectile dysfunction and reduced ejaculation, than men with LUTS only. Evaluation and treatment strategies should address this population of men with symptoms suggestive of both prostatitis and BPH.

Aged↗
PubMed1991

In situ expression of mRNA for proto-oncogenes in benign prostatic hyperplasia and in prostatic carcinoma.

Nine cases of prostatic carcinoma and 5 cases of benign prostatic hyperplasia (BPH) were examined for the in vivo expression of mRNA by an in situ hybridization technique for cellular proto-oncogenes, c-myc, c-fos, and c-sis. The latter of which encodes the B-chain of the platelet-derived growth factor (PDGF). High levels of c-myc and c-sis mRNAs were demonstrated in one highly differentiated prostatic carcinoma. Signals were localized in epithelial cells, both in packed cancer cells and in benign hyperplastic cells with glandular differentiation. A lower level of c-fos mRNA was also detected in the same areas. Four other carcinoma specimens showed c-sis mRNA, three of which also expressed c-fos mRNA. One other carcinoma expressed only c-myc mRNA. Three BPH specimens also contained c-sis and c-fos mRNA with one also exhibiting c-myc mRNA in the glandular epithelial cells. The results support the possibility that local production of growth factors, i.e. PDGF, may play a role in proliferation of prostatic epithelial cells.

Genes, myc↗
PubMed1995

[Organ culture of human tissue as study model of hormonal and pharmacological regulation of benign prostatic hyperplasia and of prostatic cancer].

We have established organ cultures of human prostate in vitro analysis of the hormone responsiveness of prostatic carcinoma. The influence of dihydrotestosterone (DHT), the epidermal growth factor (EGF) and prolactin (PRL) was assessed on the proliferation rate of 30 benign human prostatic hyperplasias (BPH) maintained for 48 hours as short-term primary cultures. The influence exerted by the EGF, the DHT and the PRL on the BPH cell proliferation was characterized by adding these compounds alone or in combination to the culture media. The proliferation rate was assessed by means of histo-autoradiographical nuclear labeling with titriated thymidine. The results show that of the DHT, EGF and PRL, the first two induced a statistically significant increase in the cell proliferation rate in a proportion of BPH significantly higher than the proportion of BPHs whose cell proliferation was increased significantly by the PRL. Furthermore, the PRL was able to antagonize the EGF-induced stimulatory effect on the BPH glandular cell proliferation rate. Lastly, the EGF- and PRL-mediated effects on the BPH glandular cell proliferation correlated with each other, while the DHT-mediated did not correlate with either the PRL- or the EGF-mediated effects. This model of organ, culture provide a basis for developing a method for in vitro testing of the individual hormone and drug responsiveness of a prostatic carcinoma.

Aged↗
PubMed1982

Endogenous androgen levels in epithelium and stroma of human benign prostatic hyperplasia and normal prostate.

5 alpha-Dihydrotestosterone (DHT) and 5 alpha-androstane-3 alpha, 18 beta-diol (3 alpha-diol) were extracted from epithelium and stroma of human benign prostatic hyperplasia (BPH) and of normal prostate and quantified by RIA. The main results were: (1) concerning the BPH, DHT is mainly located in the nuclear fraction of epithelium and stroma, whereas 3 alpha-diol was completely of extranuclear origin, (2) in the nuclei derived from BPH stroma the DHT content (7.1 +/- 0.88 pmol/mg DNA, mean +/- SEM [n = 14]) was significantly higher (P less than 0.01) than in the nuclei derived from BPH epithelium (3.8 +/- 0.38 pmol/mg DNA [n = 14]). The DHT content in the nuclear fraction derived from unseparated, i.e. whole tissue, was 5.6 +/- 0.60 pmol/mg DNA [n =14], (3) the biological significance of the overwhelming DHT accumulation in the stromal nuclei for the BPH tissue is reflected by a significant correlation between the DHT values in the nuclei from stroma and whole tissue (rs = 0.710, P less than 0.01) and (4) in four normal prostates the DHT content in the nuclear fraction of epithelium (1.3 +/- 0.37 pmol/mg DNA) and stroma (2.2 +/- 0.93 pmol/mg DNA) was significantly lower (P less than 0.01, each) compared with the respective BPH fraction. These data support earlier findings which indicate that the stroma of BPH is a preferential tissue for androgen metabolism.

Adult↗
PubMed2000

Prostate specific antigen and benign prostatic hyperplasia.

Benign prostatic hyperplasia is a common condition in males over 50 years, but prostate cancer can develop in the same population. Prostate specific antigen, the best marker for prostate cancer, is also produced by benign epithelial cells, and there is an overlapping phenomenon between both conditions. The better we understand the relationships between benign prostatic hyperplasia and prostate specific antigen, the higher will be the discrimination power of prostate specific antigen measurement as a marker for prostate cancer. Our scope includes a review of the latest published material to date on this subject.

Age Factors↗
PubMed1995

Managing patients with benign prostatic hyperplasia.

Benign prostatic hyperplasia is the usual cause of prostatism--irritative and obstructive urinary symptoms. Steps in making the diagnosis include a focused neurologic examination, urinalysis, serum creatinine determination and, possibly, catheterization to detect urinary retention. It is difficult to predict the likelihood of future complications, such as complete urinary obstruction, even for patients with severe symptoms. The natural course of prostatism is a waxing and waning of symptoms. Treatment options are watchful waiting, medication, transurethral prostatectomy, and newer surgical treatments such as microwave thermopathy and laser ablation. The family physician can counsel patients about the potential side effects of these treatments as well as the problems incurred by simply adjusting to the disabilities associated with benign prostatic hyperplasia.

Aged↗
PubMed2005

[Modern pharmacotherapy of benign prostatic hyperplasia].

Benign prostatic hyperplasia is the most common medical problem affecting elderly men throughout the world. With increasing awareness of health issues amongst males, the morbidity caused by this disease is not longer being accepted as just part of growing old. Until about 10 years ago, surgery was the only effective treatment for symptomatic benign prostatic hyperplasia. Now, many men suffering from this disorder may be effectively treated with a medical therapy. This article provides an overview of the efficacy and safety of 5alpha-reductase inhibitors, alpha1-adrenoceptor antagonists and herbal remedies, putting special emphasis on the current place of these agents in the modem therapy of benign prostatic hyperplasia. Wherever possible, our opinion is based on the detailed analysis of the results of available clinical trials.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2005

A 63 element 1.75 dimensional ultrasound phased array for the treatment of benign prostatic hyperplasia.

BACKGROUND: Prostate cancer and benign prostatic hyperplasia are very common diseases in older American men, thus having a reliable treatment modality for both diseases is of great importance. The currently used treating options, mainly surgical ones, have numerous complications, which include the many side effects that accompany such procedures, besides the invasive nature of such techniques. Focused ultrasound is a relatively new treating modality that is showing promising results in treating prostate cancer and benign prostatic hyperplasia. Thus this technique is gaining more attention in the past decade as a non-invasive method to treat both diseases. METHODS: In this paper, the design, construction and evaluation of a 1.75 dimensional ultrasound phased array to be used for treating prostate cancer and benign prostatic hyperplasia is presented. With this array, the position of the focus can be controlled by changing the electrical power and phase to the individual elements for electronically focusing and steering in a three dimensional volume. The array was designed with a maximum steering angle of +/- 13.5 degrees in the transverse direction and a maximum depth of penetration of 11 cm, which allows the treatment of large prostates. The transducer piezoelectric ceramic, matching layers and cable impedance have been designed for maximum power transfer to tissue. RESULTS: To verify the capability of the transducer for focusing and steering, exposimetry was performed and the results correlated well with the calculated field. Ex vivo experiments using bovine tissue were performed with various lesion sizes and indicated the capability of the transducer to ablate tissue using short sonications. CONCLUSION: A 1.75 dimensional array, that overcame the drawbacks associated with one-dimensional arrays, has been designed, built and successfully tested. Design issues, such as cable and ceramic capacitances, were taken into account when designing this array. The final prototype overcame also the problem of generating grating lobes at unwanted locations by tapering the array elements.

Animals↗
PubMed2000

Combined sabal and urtica extract compared with finasteride in men with benign prostatic hyperplasia: analysis of prostate volume and therapeutic outcome.

OBJECTIVE: To test the hypothesis that in patients with benign prostatic hyperplasia (BPH), the outcome of drug therapy with finasteride may be predictable from the baseline prostate volume and that positive clinical effects might be expected only in patients with prostate volumes of > 40 mL, using a subgroup analysis of results from a previously reported clinical trial of finasteride and phytotherapy. PATIENTS AND METHODS: A subgroup of 431 patients was analysed from a randomized, multicentre, double-blind clinical trial involving 543 patients with the early stages of BPH. Patients received a fixed combination of extracts of saw palmetto fruit (Serenoa repens) and nettle root (Urtica dioica) (PRO 160/120) or the synthetic 5alpha-reductase inhibitor finasteride. The patients assessed had valid ultrasonographic measurements and baseline prostate volumes of either </= 40 mL or > 40 mL. All 516 patients were included in the safety analysis. The results of the original trial showed equivalent efficacy for both treatments. RESULTS: The mean (SD) maximum urinary flow (the main outcome variable) increased (from baseline values) after 24 weeks by 1.9 (5.6) mL/s with PRO 160/120 and by 2.4 (6.3) mL/s with finasteride. There were no statistically significant group differences (P = 0.52). The subgroups with small prostates (</= 40 mL) showed similar improvements, with mean values of 1.8 (5.2) mL/s with PRO 160/120 and 2.7 (7.4) mL/s with finasteride. The mean values for the subgroups with prostates of > 40 mL were similar, at 2.3 (6.1) and 2. 2 (5.3) mL/s, respectively. There were improvements in the International Prostate Symptom Score in both treatment groups, with no statistically significant differences. The subgroup analysis showed slightly better results for voiding symptoms in the patients with prostates of > 40 mL, but there were also improvements in the subgroup with smaller prostates. The safety analysis showed that more patients in the finasteride group reported adverse events and also there were more adverse events in this group than in patients treated with PRO 160/120. CONCLUSION: The present analysis showed that the efficacy of both PRO 160/120 and finasteride was equivalent and unrelated to prostate volume. However, PRO 160/120 had better tolerability than finasteride.

Aged↗
PubMed1997

Argyrophilic nucleolar organizer regions in atypical adenomatous hyperplasias, prostatic intraepithelial neoplasias and prostatic neoplasms.

Sections from 104 cases of benign, preneoplastic and neoplastic lesions of the prostate were studied for argyrophilic nucleolar organizer regions (AgNORs). The mean NOR counts in normal controls (2.87) and benign prostatic hyperplasia with or without chronic prostatitis (4.90 and 3.84 NORs/nucleus, respectively) were found to be significantly less (p < 0.001) than that in prostatic intraepithelial neoplasia (PIN) and adenocarcinoma of the prostate (5.65 and 5.78 NORs/nucleus, respectively). The mean AgNOR count of a section with atypical adenomatous hyperplasia was significantly lower than that in PIN. No statistically significant difference was observed between AgNOR counts of high-grade PIN and well-differentiated adenocarcinoma (WDAC; 5.67 vs. 5.78 NORs/nucleus, respectively), however the difference between low-grade PIN and WDAC was statistically significant (5.46 vs. 5.78 NORs/nucleus, p < 0.005). The increase in NOR counts occurred concomitantly with the decrease in the degree of differentiation of adenocarcinoma. Thus, NOR was found to be a good adjuvant to the existing diagnostic parameters to pick up more cases at the stage of PIN when prognosis is better.

Adenocarcinoma↗