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PubMed2004

The secretion of endothelin-1 by microvascular endothelial cells from human benign prostatic hyperplasia is inhibited by vascular endothelial growth factor.

Prostate growth seems to be influenced by paracrine factors like endothelin-1 (ET-1), originating from the microvascular endothelium. Recently, we reported on the first isolation and primary culture of microvascular endothelial cells (HPEC) derived from tissue of human benign prostatic hyperplasia (BPH). Therefore, direct investigation of growth factor secretion by HPEC is now possible. BPH tissue was cut into small cubes and gently squeezed after incubation with dispase. HPEC were cultured from the resulting cell suspension after a stepwise selection by use of superparamagnetic beads coated with antibodies against endothelial specific antigens. HPEC were characterized by flow cytometry. After the incubation of HPEC either with vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-alpha), or adenosine triphosphate (ATP), the secretion of ET-1 was measured by ELISA. HPEC showed a typical endothelial morphology. They were positive for von Willebrand factor and CD31. The ET-1 secretion of HPEC was inhibited by VEGF, but was unaffected by TNF-alpha or ATP. Furthermore, histochemistry revealed that in vivo microvascular endothelial cells were negative for ET-1. Because of the suppression by the widespread VEGF, it is unlikely that ET-1 from the microvascular endothelium acts as a growth factor in human BPH.

Adenosine Triphosphate↗
PubMed2001

[Prostatic cancer developing after transurethral resection of the prostate for benign prostatic hyperplasia].

From January 1993 to June 1998, 319 cases were histopathologically diagnosed as prostatic cancer. In 7 of the 319 cases (2.2%) transurethral resection of the prostate (TUR-P) had been performed and a diagnosis of benign prostatic hyperplasia had been made with the resected specimens. The interval between TUR-P and the diagnosis of prostatic cancer ranged from 22 months to 15 years. All the cases showed an elevation of the prostate specific antigen (PSA) value (6.4-399 ng/ml, Tandem-R: RIA) at the time of cancer diagnosis. In 2 cases, PSA was measured in cancer screening. The clinical stage was stage B1 in 2 cases, stage B2 in 2 and D2 in 3. Only one case had been regularly followed-up after TUR-P, in which cancer was diagnosed by needle biopsy 22 months after TUR-P, because of the sustained high PSA values. Since most of such patients have an advanced stage of prostate cancer, it is of importance to have periodical follow-up examinations after TUR-P. The measurement of PSA appears the most reliable means in this way.

Aged↗
PubMed1994

Epidemiology of benign prostatic hyperplasia: risk factors and concomitance with hypertension.

Benign prostatic hyperplasia (BPH) is a common condition. Eighty-eight per cent of autopsy specimens from men aged over 80 years have been shown to have histological BPH. It is the cause of the commonest surgical procedure in older men (3 men in 10 may ultimately undergo prostatectomy). Despite its being such a common occurrence, little is known with any certainty about the epidemiology of BPH. The incidence, even the population prevalence, is difficult to determine for a variety of reasons. Knowledge of risk factors is sparse, and analytical epidemiological studies of BPH are difficult to conduct. Case-control studies are problematic, in that a control group may be difficult to define and a large proportion of the control group may have undiagnosed BPH. There have been reports of associations between BPH and hypertension, but there is no consistent suggestion that such an association could be causal. However, given the frequent occurrence of both conditions in ageing men, a large proportion of men may well have both diseases. With the increase in the number of men now reaching older ages it is clear that BPH, as well as hypertension, will continue to have a substantial and increasing influence in terms of morbidity, mortality and healthcare costs. The need for high-quality epidemiological information and consequent increased prospects for prevention is obvious.

Adult↗
PubMed2006

Medical and minimally invasive therapies for the treatment of benign prostatic hyperplasia.

Over the last decade, management of benign prostatic hyperplasia (BPH) has changed with a substantial decrease in the use of transurethral prostatectomy (TURP) and a simultaneous increase in the use of medical therapy and minimally invasive surgical therapy (MIST). The goal of management of this chronic progressive condition is not only to provide relief of lower urinary tract symptoms (LUTS) but also to reduce the lifetime risk of adverse outcomes. Recent clinical evidence has demonstrated a clear role for medical therapy, particularly with 5-alpha-reductase inhibitors (5ARIs) either alone or in combination with alpha-blockers, to reduce the risk of acute urinary retention and need for surgery and provide symptom relief. Clinical data on MISTs also indicate a more pronounced short-term effect; however, the long-term durability of these therapies remains uncertain. Minimally invasive surgical therapies confer treatment benefits in a single 1-h treatment session under local anesthesia. Recovery times and adverse events are improved compared with TURP, but issues such as hematuria, prolonged catheterization, urinary tract infection and retreatment remain commonly reported issues. Today, urologists are faced with the challenge of identifying the most appropriate treatment option for the long-term management of BPH. The initial choice for any given patient will depend on his presenting circumstances and the influence of treatment risks on these circumstances. Providing patients with informed treatment decisions is a key element of management.

Antineoplastic Agents↗
PubMed1999

The relative amount of epithelium, muscle, connective tissue and lumen in prostatic hyperplasia as a function of the mass of tissue resected.

PURPOSE: The relative amounts of epithelium, connective tissue, muscle and gland lumen in benign prostatic hyperplasia have been reported but they have not been correlated with prostate size. We determine if the relative amount of prostatic tissue varies with prostate size. MATERIALS AND METHODS: Paraffin blocks of transurethrally resected prostate tissue were randomly chosen from the archives of 58 patients with benign prostatic hyperplasia. Two new slides per patient were made and stained with prostate specific antigen or Masson trichrome, respectively. A total of 20 images from each slide were captured using a high resolution camera, digitized and analyzed with computer software for the relative percentage of the various tissue components. RESULTS: As the amount of prostate tissue resected increased from less than 10 to greater than 70 gm. the epithelium had a 4-fold increase from 5.37 to 21.92%, the muscle component had a 42% decrease from 28.46 to 16.62%, the lumen doubled from 7.05 to 14.01% and the connective tissue remained relatively unchanged from 35.58 to 31.53%. There was a statistically significant difference in all components of prostatic tissue except for connective tissue when comparing prostates less than 30 versus greater than 30 gm., including epithelium 6.52 versus 16.10% (p <0.01), muscle 28.45 versus 20.78% (p <0.01), lumen 7.42 versus 14.58% (p <0.01) and connective tissue 35.74 versus 32.45% (p <0.06). The stroma-to-epithelium and muscle-to-epithelium ratios each had a 9-fold decline (p = 0.01). CONCLUSIONS: As the prostate increases in size, there is statistically significant more epithelium and lumen, and less muscle tissue.

Connective Tissue↗
PubMed1999

Prostatic intraepithelial neoplasia and apoptosis in benign prostatic hyperplasia before and after the Chernobyl accident in Ukraine.

The prevalence of prostatic intraepithelial neoplasia (PIN) in men who underwent surgery for benign prostatic hyperplasia (BPH) before and after the Chernobyl nuclear accident was studied. BPH samples were obtained by adenomectomy from 45 patients operated in 1984 before the accident (Group I), and 47 patients from the low contaminated Kiev City (Group II) and 76 from high contaminated area (Group III) operated between 1996 and 1998. Their BPH samples were examined histologically and immunohistochemically. The incidences of prostatic intraepithelial neoplasia (PIN) and high grade PIN (HGPIN) were 15.5 and 11.1% in Group I, 29.8 and 14.9% in Grpoup II, and 35. 5 and 19.7% in Group III. The difference between the incidences of PIN in Group I and III is significant (p<0.02). There was increased apoptosis in areas of PIN in Group II and III as compared to Group I (p<0.001). Since apoptosis has been shown to be associated with ionizing radiation and it is now found to be associated with PIN in patients diagnosed after the Chernobyl nuclear accident, this suggests that long-term low dose internal ionizing radiation potentially may cause prostate cancer.

Apoptosis↗
PubMed2000

Atrophic effects of antiandrogen, chlormadinone acetate (CMA) on dog prostate with spontaneous benign prostatic hyperplasia.

The atrophic effect of a synthetic steroidal antiandrogen, chlormadinone acetate (CMA), on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Male beagle dogs (5-8 years old) were divided into four experimental groups. Group 1 consisted of untreated controls. Groups 2 to 4 received CMA 0.03, 0.1, and 0.3 mg/kg/day, p.o., respectively, for 6 months. In group 1, glandular hyperplasia of the prostate was clearly detected. The glandular epithelial cells showed uniformly intense nuclear staining for androgen receptor (AR). AR was also localized in the nuclei of the fibro-muscular stromal cells. Immunoreactivity of 5 alpha-reductase type I was positive in most glandular epithelial cells. No fibro-muscular stromal cells were stained. Immunolocalization of 5 alpha-reductase type II was clearly detected in the interacinar fibro-muscular stromal cells, but not in the glandular epithelial cells. In groups 2 to 4, CMA produced marked atrophy of the glandular epithelium. The interacinar fibro-muscular stroma was prominent. The nuclear staining for AR in both epithelial and stromal cells was remarkably decreased. Furthermore, the immunoreaction for 5 alpha-reductase type I in most glandular epithelial cells was negative or very weak. The immunoreaction of 5 alpha-reductase type II in the interacinar fibro-muscular stromal cells was negative or very weak. These results indicate that the uptake of testosterone and/or its androgenic effect on the prostate may be suppressed by CMA. The decreased AR-immunostaining may be explained by the decrease in the number of AR and/or antibody binding sites for AR. Therefore, the atrophy after treatment with CMA may be due to shrinkage of both glandular and stromal compartments in the prostate tissue.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2003

In vivo characterization of a prostate-specific antigen promoter-based suicide gene therapy for the treatment of benign prostatic hyperplasia.

To develop a novel gene therapeutic modality for the effective treatment of benign prostatic hyperplasia (BPH), we investigated the properties of toxic gene therapy utilizing prostate-specific antigen (PSA) promoter driving herpes simplex virus thymidine kinase (HSV-TK) suicide gene to induce highly selective molecular ablation of epithelial cells with minimal systemic toxicity in canine prostate. Replication-defective recombinant adenoviral vectors containing HSV-TK gene under transcriptional control of long PSA promoter (Ad-PSA-HSV-TK) were developed and delivered in an situ manner. Briefly, laparotomies were performed and Ad-PSA-HSV-TK (1 x 10(9) PFUs) was injected into the left lateral lobe of prostate only on days 1 and 7 with appropriate prodrug acyclovir in adult Beagle dogs. The therapeutic efficacy was evaluated on the 56th experimental day. The striking apoptosis of epithelial cells was identified in the treated left half of canine prostate on TUNEL assay. On immunohistochemical studies, there was markedly decreased number of PSA-secreting epithelial cells compared to control. Also significant atrophy of prostate glands, associated with dense infiltration of lymphocytes and plasma cells, was identified in the treated side. The PSA promoter-based suicide gene therapy induced highly selective and definite ablation of epithelial cells in benign canine prostate. Our novel approach could open opportunity of gene therapeutic modality for the treatment of clinical BPH.

Acyclovir↗
PubMed2005

Repeated intensification of lower urinary tract symptoms in the patient with benign prostatic hyperplasia during bisoprolol treatment.

A case of a 60-year-old male patient, suffering from benign prostatic hyperplasia (BPH), with deterioration of lower urinary tract symptoms (LUTS) during antihypertensive treatment with bisoprolol was presented. Discontinuation of beta-blocker resulted in giving a relief whereas the resumption of its use caused repeated deterioration. Bisoprolol deteriorated lower urinary tract symptoms in patient with benign prostatic hyperplasia. Increase of lower urinary tract symptoms caused by beta-blockers can be more significant in elderly men.

Adrenergic beta-Antagonists↗
PubMed2004

[Clinic analysis of repeat prostatectomy after transurethral prostatectomy for benign prostatic hyperplasia].

OBJECTIVE: To analyze the incidence rate of repeat transurethral prostatectomy (TURP) and its probable causes after TURP for benign prostatic hyperplasia (BHP). METHODS: A retrospective study was conducted to summarize the cases who received repeat transurethral resection of prostate after TURP for benign prostatic hyperplasia in recent 20 years. The data were compared with the data of the cases who just received once TURP for BPH. RESULTS: 1225 patients received TURP for BHP from 1981 to 2001. Fifty-seven patients experienced repeat transurethral resection of the prostate after a mean interval of 3 years and 2 months with an incidence rate of 4.65%. 69.8% of which manifested repeat gross hematuria before repeat prostatectomy, with a rate significantly higher than the general gross hematuria rate and the gross hematuria rate at the first admission (P < 0.005 and P < 0.01). CONCLUSION: The incidence rate of repeat prostatectomy after TURP for BHP is 4.65%. The mean interval between the two procedures is 3 years and 2 months. Gross hematuria is one of the main causes for repeat TURP besides the low urinary tract symptoms.

Aged↗
PubMed1997

Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia.

Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer, an equal number of cases of benign prostatic hyperplasia (BPH) and an equal number of apparently healthy control subjects. The three groups were matched for age and town of residence in the greater Athens area. Steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1 (IGF-1) were measured in duplicate by radioimmunoassay in a specialized US centre. Statistical analyses were performed using multiple logistical regression. The results for IGF-1 in relation to prostate cancer and BPH were adjusted for demographic and anthropometric factors, as well as for the other measured hormones. There was no relation between IGF-1 and BPH, but increased values of this hormone were associated with increased risk of prostate cancer; an increment of 60 ng ml(-1) corresponded to an odds ratio of 1.91 with a 95% confidence interval of 1.00-3.73. There was also some evidence for an interaction between high levels of testosterone and IGF-1 in relation to prostate cancer. This finding suggests that, in addition to testosterone, IGF-1 may increase the risk of prostate cancer in humans.

Aged↗
PubMed1986

Development of canine benign prostatic hyperplasia with age.

The prevalence and growth of benign prostatic hyperplasia (BPH) in beagles as a function of age were studied. The normal prostate gland was 12 +/- 3 gm in beagles 2.1-3.0 years of age; this weight remained unchanged unless BPH developed. Histologic evidence of BPH developed at an early age with a prevalence of 16% of the dogs by the age 2 years. Fifty percent of the dogs had BPH, determined histopathologically by age 4.1-5.0 years. The average weight of the prostate gland remained constant until after age 8 years. With age, the pathologic features of BPH changed from glandular to the complex form, with no increase in prostate weight until after 8 years. Reinitiation of growth occurred and prostate weight increased to greater than 36 gm in eight of 185 beagles older than age 8 years.

Aging↗
PubMedDate not supplied

[One-stage transurethral resection of the urinary bladder and the prostate in patients with superficial cancer of the urinary bladder combined with benign prostatic hyperplasia].

Combination of urinary bladder cancer (UBC) with benign prostatic hyperplasia (BPH) is a prognostically unfavourable factor. To assess clinical efficacy of one-stage transurethral resection of UBC and BPH in combination with adjuvant immunotherapy, we examined 181 patients with UBC stage Tis, Ta-T1 and BTH. All the patients have undergone one- and two-stage endoscopic operations. TUR of the urinary bladder and the prostate was made in 87 patients. Stage-by-stage TUR of the urinary bladder and TUR of the prostate were made in 94 controls. We conducted postoperative immunotherapy with BCG vaccine (imuron) as an adjuvant therapy in 114 (63%) patients. Postoperative UBC recurrence occurred in 124 (68.5%) patients: 49 (56.3%) patients of the study group and 75 (79.7%) controls (p < 0.05). Reoperation (TUR of the urinary bladder) was performed in all cases of UBC recurrence. Five-year survival in the study group was 71% and 68.0% survived in the control group (p > 0.05). The conclusion is made that in combination of superficial UBC with BPH indications appear for TUR of the urinary bladder and TUR of the prostate with adjuvant immunotherapy. Early elimination of infravesical obstruction lowers UBC recurrence rate and improves the patients' quality of life.

Adjuvants, Immunologic↗
PubMed2006

Noninvasive treatment of benign prostatic hyperplasia. Where do we stand in 2005.

Noninvasive treatment of lower urinary tract symptoms LUTS due to benign prostatic hyperplasia BPH includes self-management and medical treatment. Self-management should be encouraged as an initial step for all men with uncomplicated LUTS/BPH. It consists of 3 elements, namely: education and reassurance, lifestyle modification of fluid intake and concurrent medical therapy and finally behavioral interventions including management of post-void dribbling and bladder retraining. If self-management fails, medical or surgical interventions are required. Further, research is required to define and test the effectiveness of self-management either as a primary intervention or to augment existing medical therapies. Benign prostatic hyperplasia patients in need of rapid onset of symptom relief and those with small prostates benefit from the use of alpha-blockers. Although 5-alpha-reductase inhibitors 5 ARIs provide symptomatic benefits, the onsets of these are slower than those observed with the alpha-blockers. Amongst available therapies, only 5 ARIs have been shown to reduce the risk of acute urine retention AUR and BPH-related surgery compared to placebo. The Medical Therapy of Prostatic Symptoms MTOPS Study provides rational basis for combined alpha-blockers plus 5 ARIs in patients with a high index of disease progression prostate volume >30 g and prostate-specific antigen >1.6 ng/ml. Preliminary studies suggest that anticholinergics could be safe in LUTS/BPH and can help to alleviate irritative bladder symptoms due to overactive bladders commonly associated with BPH.

Adrenergic alpha-Antagonists↗
PubMed1993

Needle ablation using radio frequency current as a treatment for benign prostatic hyperplasia: experimental results in ex vivo human prostate.

Transurethral needle ablation of the prostate using low level radiofrequency (RF) energy was investigated in a human ex vivo model. RF power applications at a variety of power levels for various treatment times elicited marked thermal lesions of consistent sizes in prostatic adenomas. Tissue temperature was found to be the fundamental lesioning parameter. Lesions were created whenever tissue temperature exceeded 45 degrees C. Lesion size correlated with RF power delivery and electrode length. Monitoring of the tissue impedance assisted in controlling efficacious lesioning. RF power applications of 5-7.5 W for 3 min are suggested as the 'ideal' setting to treat human prostatic adenomas, taking into consideration the lesion size and time to achieve ablative temperatures.

Aged↗
PubMed2001

Regional variations of insulin-like growth factor I (IGF-I), IGF-II, and receptor type I in benign prostatic hyperplasia tissue and their correlation with intraprostatic androgens.

Benign prostatic hyperplasia (BPH) is an androgen-dependent disease; it originates exclusively in the inner prostate, which includes tissue surrounding the urethra. Stromal-epithelial interaction has a pivotal role in the regulation of the development and growth of the prostate, and locally produced peptide growth factors are considered important mediators of this interaction. Insulin-like growth factor I (IGF-I) and IGF-II, acting mainly through type 1 IGF receptor (IGFR1), have mitogenic and antiapoptotic effects on epithelial and stromal prostatic cells. In this study the expression of IGF-I, IGF-II, and IGFR1 messenger ribonucleic acid (mRNA), the immunoreactive content of IGF-I (irIGF-I) and IGF-II (irIGF-II) were determined in periurethral, intermediate, and subcapsular regions of BPH tissue to verify their possible regional variation; a correlation to the tissue levels of dihydrotestosterone (DHT) and 3 alpha-androstanediol (3 alpha Diol) was also determined to verify their possible androgen dependence. Prostates were removed by suprapubic prostatectomy from 14 BPH patients and sectioned in the periurethral, intermediate, and subcapsular regions. Gene expression of IGF-I, IGF-II, and IGFR1 was evaluated by semiquantitative RT-PCR, using beta-actin as a control. irIGF-I was measured by RIA, and irIGF-II was measured by IRMA after acidification and chromatography on Sep-Pak C(18) cartridges. DHT and 3 alpha Diol concentrations were evaluated by RIA after extraction and purification on Celite microcolumns. IGF-II and IGFR1, but not IGF-I, mRNA was higher in the periurethral than in the intermediate (P < 0.05) and subcapsular (P < 0.01) region. Also, prostatic levels of irIGF-II, expressed as picomoles per g tissue, were higher in the periurethral (20.84 +/- 1.84) than in the intermediate (14.81 +/- 2.11; P < 0.05) and subcapsular (10.88 +/- 1.21; P < 0.001) region. No significant differences were found in irIGF-I content. Considering prostatic androgen levels, DHT and 3alphaDiol presented a regional variation, with the highest concentrations in the periurethral region. IGF-II mRNA and irIGF-II levels were positively correlated with both DHT and 3 alpha Diol content. These results demonstrate that in BPH tissue a greater IGF-II activity is present in the periurethral region, the site of origin of BPH. Moreover, we can hypothesize that the tissue androgen content may modulate prostatic production of IGF-II, acting at the transcriptional and probably the posttranscriptional level. Therefore, even though further studies will need to confirm this hypothesis, DHT may increase IGF-II activity, mainly in the periurethral region, which, in turn, induces, through IGFR1, benign proliferation of both epithelial and stromal cells, characteristic of BPH.

Aged↗
PubMed1995

Microwave therapy of benign prostatic hyperplasia.

Thermotherapy of the prostate proves to be a safe and effective treatment for patients with symptomatic prostatism secondary to BPH. Present treatment regimens yield results and side effects intermediate between drug therapy and prostatectomy. Future enhancements of the thermotherapy technique are likely to improve its results to the level of surgery.

Aged↗