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Increased risk of prostate cancer and benign prostatic hyperplasia associated with transforming growth factor-beta 1 gene polymorphism at codon10.

Transforming growth factor-beta 1 (TGF-beta1) plays a significant role in regulating the proliferation and apoptosis of prostate epithelial and stromal cells. We explored the association between the T (Leu) to C (Pro) polymorphism at codon10 of the TGF-beta1 gene (TGFB1) and the risk of prostate cancer (PCa) or benign prostatic hyperplasia (BPH) in 351 PCa patients, 221 BPH patients and 303 male controls in Japan. There were significant differences in the CC versus TC + TT genotype distribution between PCa patients and male controls (P=0.008), and between BPH patients and male controls (P=0.041). Males with the TC or TT genotype had a 1.62-fold increased risk of PCa [95% confidence interval (95% CI)=1.14-2.30, P=0.007] and a 1.51-fold increased risk of BPH (95% CI=1.02-2.24, P=0.041) compared with those with the CC genotype, therefore suggesting the dominant effect of the TGFB1 T allele on development of PCa and BPH. There were no significant differences in the TGFB1 genotype distribution between different groups of tumor grades and stages in the PCa patients and no significant differences when PCa patients were stratified by the age of onset. The results suggest that the codon10 polymorphism in TGFB1 may have a significant influence on the development of PCa and BPH, therefore underscoring the importance of the TGF pathway in the development of these prostatic diseases. However, it appeared to have no impact on the disease status or age of onset of PCa.

Aged↗

[Conservative, non-hormonal treatment of benign prostatic hyperplasia].

The indications for and efficacy of non-hormonal drugs in the treatment of benign prostatic hyperplasia (BPH) are the subject of some controversy. However, a critical evaluation of the available literature shows that no clinically relevant reduction of prostatic size has been reached with any drug tested so far. It is suggested that alpha-adrenergic blockers exert a beneficial effect by reducing the "dynamic" component associated with prostatic obstruction. The application of objective criteria has not shown cholesterol-lowering and phytotherapeutic drugs to have any significant and clinically relevant advantage over placebos. The evaluation of drug therapy in BPH patients is complicated by the fact that the obstructive signs are masked by irritative symptoms ("prostatism", "unstable bladder"), the causes of which are also unknown. A causal drug therapy should have an impact on biochemically and/or biologically confirmed changes that are responsible for the development of BPH. Als long as the cause of BPH remains unknown, drugs cannot fulfil these requirements. The efficacy of drug therapy in patients with BPH can only, therefore, be evaluated in double blind controlled studies including modern urodynamic investigations. However, these standards should also be applied to the decision as to whether operative treatment is indicated and to evaluation of the results.

Adrenergic alpha-Antagonists↗

Origin and structure of benign prostatic hyperplasia.

The development of microradiography of the prostate gland has provided a new approach to investigating the origin and structure of benign hyperplasia. It has demonstrated that benign prostatic hyperplasia is usually microadenomatous in structure, although reticular types do occur. It originates at the lateral boundary of the periurethral muscle in the position of the transitional zone. In contrast, stromal nodules are homogeneous and amorphous in structure and develop at the site of the short straight urethral ducts within the periurethral muscle.

Adolescent↗

[Combination therapy in benign prostatic hyperplasia (BPH)].

Because of the constant progress in our understanding of the physiopathology of benign prostatic hyperplasia, it is now possible to propose a more rational use of combination therapy, which is often used empirically, though not recommended, in routine practice. This chronic disorder, which is in fact more complex than it appears, may benefit in theory from a combination of molecules with different complementary action mechanisms. Prostatic obstruction may be treated either by alphablockers with their peripheral muscle-relaxant action on the smooth muscle fibers of the prostate and bladder neck, or by 5-alpha-reductase inhibitors for their reducing effect on gland volume. Irritative bladder symptoms involving the detrusor may be treated by antimuscarinics and to a lesser extent by alphablockers. Currently available data from recent studies suggest that a combination of an alphablocker and a 5-alpha-reductase inhibitor may be useful in patients with symptomatic BPH and a prostate of more than 40 grams with PSA > 1.6 ng/ml. Combinations including an antimuscarinic are effective in patients with BPH with marked irritative symptoms. Finally, the combination of an alphablocker and a phosphodiesterase type 5 inhibitor may be useful in patients with lower urinary tract symptoms (LUTS) associated with erectile dysfunction.

Adrenergic alpha-Antagonists↗

Controlled-release doxazosin in the treatment of benign prostatic hyperplasia.

PURPOSE: To evaluate the effectiveness and safety of controlled-release doxazosin for benign prostatic hyperplasia (BPH). SCOPE: In this open-label, noncontrolled, observational surveillance study, 3684 men with BPH received 4-8 mg of controlled-release doxazosin gastrointestinal therapeutic system (GITS) for 6 months; 3283 (89.1%) patients completed the trial. Changes in urinary symptoms and quality of life were assessed using the International Prostate Symptom Score (IPSS). Blood pressure and adverse events were assessed. CONCLUSION: After 6 months' treatment with doxazosin GITS resulted in significant improvements in IPSS. BP was reduced only in hypertensive patients. Doxazosin, GITS was well tolerated.

Aged↗

Benign prostatic hyperplasia. New concepts in the 1990s.

Many newer treatments are now being proposed for benign prostatic hyperplasia (BPH). Although patients with mild symptoms that do not interfere with their lifestyle can be periodically observed for progression, two classes of medication are being used for those with mild to moderate symptoms: alpha-adrenergic blocking agents and androgen suppressants. In patients with severe BPH, transurethral resection of the prostate is still the standard of care in the United States, but a number of new procedures have been introduced in recent years, including balloon dilation of the prostate, laser prostatectomy, use of prostatic stents, and microwave hyperthermia. Studies of the molecular biologic events leading to the development of BPH should clarify our understanding of a condition that was once often ignored.

Adrenergic alpha-Antagonists↗

[Use of proscar in preoperative preparation of patients with benign prostatic hyperplasia before transureteral resection].

Effects of proskar-MSD used before transurethral resection (TUR) of the prostate in patients with benign prostatic hyperplasia (BPH) were studied with specification of the drug action on hematuria during and after operation. Patients with histologically verified BPH received proskar for 3 and 6 months in a dose of 5 mg/day. Control patients did not receive preoperative proskar. Of patients who received proskar for 3 months, TUR with estimation of the intraoperative blood loss and changes in microcirculation and structure of prostatic tissue induced by proskar was made in 20 patients (mean age 68 years). A 3-month course of proskar reduced prostatic volume and its hyperplasia by 18-20 cm3, on the average. Mean blood loss was about 111 ml vs control 223 ml. Dopplerography revealed consolidation of adenomatous tissue and decline of volumic blood flow in the prostate after 3-month proskar course. Thus, preoperative proskar administration before TUR of prostatic adenoma results in sclerosing of prostatic tissue, decrease of microcirculation manifesting intraoperatively with diminished hematuria and less number of subsequent complications; promotes a favourable outcome of the operation; improves life quality.

Combined Modality Therapy↗

Interstitial laser coagulation for management of benign prostatic hyperplasia: a Japanese experience.

PURPOSE: The principle of interstitial laser coagulation is to shrink the prostate by generating intraprostatic necrosis without damaging the urethra or causing tissue sloughing. The clinical efficacy and durability of interstitial laser coagulation in the treatment of benign prostatic hyperplasia (BPH) were evaluated. MATERIALS AND METHODS: From December 1993 to June 1996, 76 patients with symptomatic BPH were treated with interstitial laser coagulation. A neodymium:YAG laser was used in combination with a specially designed interstitial thermotherapy light guide. The tip of the light guide was inserted into each lobe of the prostate transurethrally under direct vision. All evaluations were made at baseline and then 1, 3, 6 and 12 months after therapy. Treatment outcome was evaluated by International Prostate Symptom Score (I-PSS), flow rate and post-void residual urine volume. Disease specific quality of life was assessed via a quality of life assessment score and a BPH impact index. Independent of symptom assessment, a self-reporting questionnaire was prepared at 3 months postoperatively regarding satisfaction with treatment and sexual function. RESULTS: Among 44 patients followed to 12 months the mean I-PSS significantly decreased from 20.4 at baseline to 7.4, representing 64% improvement (p <0.001). Peak flow rate increased by 50% from a preoperative average of 7.4 to 11.1 ml. per second at 12 months in 42 patients (p <0.001). The post-void residual volume decreased by 57% from 102 to 44 ml. at 12 months in 40 cases (p <0.001). Steady and progressive improvement was observed on quality of life assessment and BPH impact index scores at 3, 6 and 12 months. No patients reported new onset of erectile dysfunction. No serious side effects were observed, except for loss of ejaculation in 3 cases and seminal vesicle abscess in 1. Only 6 patients (8%) required re-treatment for persisting obstructive symptoms during 12 months of followup. A recent change in methods towards more aggressive treatment plausibly influenced the outcomes to require less repeat treatment. CONCLUSIONS: After the interstitial laser coagulation procedure satisfactory results were obtained and improvement lasted through 12 months. Although the optimal number of fiber placements for each prostate is not known, more aggressive treatment appears to provide better outcomes.

Aged↗

Randomised evaluation of alternative electrosurgical modalities to treat bladder outflow obstruction in men with benign prostatic hyperplasia.

OBJECTIVES: To compare and evaluate the clinical and cost-effectiveness of transurethral vaporisation of the prostate (TUVP), a new electrosurgical modality, with the standard treatment, transurethral resection of the prostate (TURP). DESIGN: A multicentre randomised controlled trial of pragmatic design with associated economic evaluation using cost minimisation. SETTING: Patients were recruited from four centres in south-east England. PARTICIPANTS: Men requiring surgery for lower urinary tract symptoms deemed to be due to benign prostatic hypertrophy. INTERVENTIONS: TURP was performed and subsequent management conducted according to the usual practice of the clinical team. TUVP was performed with the most promising available equipment using a technique described in the literature. Postoperative management after TUVP was left to the ward team, who were not necessarily informed to which treatment arm the patient had been allocated. For the purpose of the study, patients were assessed clinically, by questionnaire and investigation at baseline, 2 months and 6 months after randomisation. A long-term follow-up postal questionnaire was sent to each patient at 2 years. For the economic evaluation, direct costs from the NHS viewpoint were collected. MAIN OUTCOME MEASURES: A reduction of at least 5 from the International Prostate Symptom Score (IPSS) was taken as a satisfactory outcome. The IPSS quality of life (QoL) question provided disease-specific information about QoL. Secondary outcome measures included urinary flow rate, post-void urinary volume, prostate volume and pressure-flow urodynamics. Questionnaires used included SF-36, EuroQol and a sexual function section based on the International Continence Society 'Benign Prostatic Hyperplasia' (ICS-BPH) questionnaire. Measurement of full blood count and urea and electrolytes was made at baseline and at 24 hours. Adverse events were recorded during the hospital stay and at follow-up visits. RESULTS: TURP and TUVP were both effective in producing a clinically important reduction in IPSS and positive change in the IPSS QoL question. The success rate for relief of symptoms was 85% for TURP and 74% for TUVP. Neither the success of the treatment nor the change in aggregated IPSS was significantly different between the groups. The improvement was sustained to 24 months after treatment with no significant difference between the groups. The effectiveness of both treatments was also equivalent when assessed through improvement in objective measures of urinary tract function, reduction in prostate size and the change in health questions of SF-36. The absolute incidence of adverse events was similar between the two groups. The incidence of severe or prolonged bleeding was less with TUVP, as evidenced by the need for blood transfusion and the drop in haemoglobin level 24 hours postoperatively. TURP and TUVP are broadly equivalent in direct NHS resource use. This study did not show any significant difference in inpatient stay or use of outpatient resources between the groups. The disposable electrodes used for TUVP are more expensive than reusable TURP electrodes. CONCLUSIONS: TURP and TUVP are equivalently effective in improving the symptoms of benign prostatic enlargement over at least 2 years. TUVP is associated with less morbidity due to haemorrhage than TURP. Replacement of TURP by TUVP would not produce a significant cost benefit to the NHS unless a reduction hospital inpatient stay of at least 1 day could be secured. Further research is necessary to determine why patients stay in hospital after transurethral surgery to the prostate and how a reduction in the length of stay can be achieved. A much larger observational study/audit is required to assess the incidence of infrequently occurring adverse events after TUVP. Longer term follow-up is also needed.

Aged↗

Clinical significance of alpha1-adrenoceptor selectivity in the management of benign prostatic hyperplasia.

Alpha1-adrenoceptor antagonists have been shown to provide effective relief from symptoms of benign prostatic hyperplasia (BPH) with attendant improvements in quality of life. Although the alpha1A-adrenoceptor subtype predominates over other subtypes of alpha1 adrenoceptors in the prostate gland, there is no evidence that a subselective alpha-adrenoceptor antagonist provides a clinical advantage over a selective alpha1-adrenoceptor antagonist in the treatment of patients with BPH. The pharmacokinetic profiles of alpha1A-adrenoceptor antagonists and their documented penetration of the blood-brain barrier (CNS adverse effects) preclude a clinical benefit of subselective alpha-adrenoceptor blockers over selective alpha1 blockers.

Adrenergic alpha-Antagonists↗

Angiotensin AT(4) receptors in the normal human prostate and benign prostatic hyperplasia.

The cellular localisation and expression of angiotensin AT(4) receptors was examined in the normal human prostate and benign prostatic hyperplasia (BPH) by quantitative in vitro autoradiography using [(125)I]-Ang IV. In the normal human prostate, AT(4) receptors were localised to the glandular epithelium. Interestingly, specific AT(4) receptor binding was significantly reduced in BPH compared to the normal prostate, as quantitated macroscopically (normal: 5038+/-476 dpm/mm(2), n=6 vs BPH: 2701+/-176 dpm/mm(2), n=6, P<0.001) and microscopically (normal: 7.28+/-0.36 grains/mm(2), n=6 vs BPH: 2.50+/-0.47 grains/mm(2), n=6, P<0.001). The findings of the present study demonstrate the presence of AT(4) receptors in the human prostate, being localised to the glandular epithelium, which suggest that the Ang IV/AT(4) system may play a role in the regulation of ionic transport and glandular secretion in the human prostate. The observation that AT(4) receptors appear reduced in BPH suggests that the AT(4) receptor may undergo agonist-induced receptor internalisation, possibly due to increased local tissue levels of Ang IV in BPH.

Autoradiography↗

Interstitial laser coagulation treatment of benign prostatic hyperplasia: is it to be recommended?

PURPOSE: To update the clinical data on the treatment of benign prostatic hyperplasia (BPH) by interstitial laser coagulation (ILC). MATERIAL AND METHODS: In addition to recent review articles, original papers published during the last 2 years were surveyed. The focus was on prospective, particularly randomized, trials and on those with long-term follow-up. RESULTS: Interstitial laser coagulation is feasible, although considerable variability is observed in the results. Operative complications are minimal, but the postoperative catheterization time is relatively long. Irritative symptoms can last for a long time, and the rate of urinary infections is as high as 35%. There also is significant variability in the urodynamic results. The technique seems to be more effective in patients with mild bladder outlet obstruction at baseline. The retreatment rate at 1 year is as high as 15%, and higher rates, as much as 40%, are described at 3 years. When compared in a randomized fashion with transurethral resection of the prostate (TURP), the postoperative period is shorter after TURP and the retreatment rate (early and late) is higher after ILC. CONCLUSIONS: Interstitial laser coagulation is superior to TURP in terms of operative morbidity, but postoperative morbidity is higher after ILC. Long-term durability has not been properly documented, and randomized studies show a higher retreatment rate after ILC than after TURP. The technique is recommended for those patients with bleeding disorders necessitating an interventional therapy.

Clinical Trials as Topic↗

[Role of growth factors in the etiopathogenesis of benign prostatic hyperplasia].

A comment is made on the role growth factors play on the regulation of prostate growth. These factors require the mediation of an specific membrane receptor to which they have to bind in order to exercise their action correctly. The objective of the present job is to carry out a comprehensive review of each and every growth factor involved in prostate growth: family of the epidermal growth factor, family of the beta-transforming growth factor, and family of the fibroblast growth factor. As a final conclusion, it should be mentioned that the two prostate growth-regulating factors more extensively studied and with greater etiopathogenic relevance in benign prostate hyperplasia, are the epidermal growth factor and, more particularly, the fibroblast growth factor.

Epidermal Growth Factor↗

Prostatic spiral versus prostatic urolume wallstent for urinary retention due to benign prostatic hyperplasia. A long-term comparative study.

Thirty-eight high-risk surgical patients with urinary retention due to benign prostatic hyperplasia (BPH) were treated by placement of a prostatic spiral under local anesthesia (group 1: 20 patients) or a prostatic stent under intravenous sedation (group 2: 18 patients). At the 1-year follow-up, mean peak flow rate, residual urine volume and subjective symptoms scale were significantly better in the stent group (p < 0.01). The rate of postoperative urinary incontinence and dislocation of the device was greater in the spiral group. Cystoscopic manipulation and removal of the device were definitely easier with the spiral. Both the prostatic spiral and stent have specific roles in the treatment of urinary retention in the unfit BPH patient. The selection of the most suitable device depends on accurate patient assessment.

Aged↗

Vascular endothelial growth factor (VEGF) expression in prostate cancer and benign prostatic hyperplasia.

PURPOSE: Vascular endothelial growth factor (VEGF) is a potent inducer of endothelial cell growth and is expressed at elevated levels in several tumor types. In this study immunohistochemical localization and distribution of isoforms of VEGF were examined in malignant and non-malignant human prostatic tissues. MATERIALS AND METHODS: Immunohistochemical localization of VEGF was performed on thirty well, moderately and poorly differentiated stage D2 prostate cancer specimens and twenty benign prostatic hyperplasia (BPH) specimens. VEGF mRNA was determined by polymerase chain reaction and VEGF protein isoforms were detected by Western blotting of prostate cancer and BPH specimens. RESULTS: Cytoplasmic immunoreactivity for VEGF was detected in tumor cells and peritumoral stromal cells of prostate cancer specimens and in non-malignant glandular epithelial cells and interglandular stromal cells in BPH specimens. Staining was focal with areas of strongly to weakly stained cells adjacent to negatively staining areas. mRNA's for VEGF121, VEGF165 and VEGF189 were present in all benign and malignant prostate specimens. VEGF protein isoforms of molecular sizes corresponding to VEGF165 and VEGF189 were detected in cytosolic extracts of prostate cancers and BPH specimens by Western blotting. In addition, two novel higher molecular weight immunoreactive bands were detected in the prostate specimens. CONCLUSIONS: Widespread distribution of VEGF in prostate cancers and BPH specimens suggest that the VEGF165, VEGF189 isoforms and novel 90 and 110 kD forms detected may contribute to the establishment or progression of these conditions.

Blotting, Western↗

Initial human clinical experience with diode laser interstitial treatment of benign prostatic hyperplasia.

OBJECTIVES: To report the initial results of treatment of outlet obstruction induced by benign prostatic hyperplasia (BPH) using interstitial laser coagulation performed with the Indigo 830 nm diode laser system. METHODS: A group of 112 men with lower urinary tract symptoms caused by BPH underwent treatment with the Indigo 830 nm laser system between October 1994 and November 1995. Patients were assessed prior to treatment and at specified post-treatment intervals for symptom score, uroflow, postvoid residual, and prostate volume. Adverse events and changes in laboratory parameters were monitored at each post-treatment visit to investigate safety of the procedure. RESULTS: Symptom score decreased from 20.9 at initial measurement to 9.6 at 3 months after procedure and 7.9 at 6 months. Uroflow rate increased from 8.0 mL/s initially to 15.2 and 14.2 mL/s at 3 and 6 months, respectively. Residual bladder volumes decreased from 105 mL initially to 59 and 38 mL at 3 and 6 months, respectively. There were no major complications (impotence, sustained incontinence, significant blood loss). Minor complications occurred in a small number of patients but were generally associated with urinary tract infection in patients with catheters. Three patients (2.7%) required retreatment and underwent transurethral resection of the prostate. CONCLUSIONS: Interstitial laser coagulation using an 830-nm diode laser system appears to be a promising new treatment, with substantial improvements in objective and subjective parameters of obstruction and a favorable side-effect profile.

Aged↗

[Cost-effectiveness analysis of the treatment of moderate benign prostatic hyperplasia].

OBJECTIVES: To estimate the most cost-effective alternative of treatment of moderate benign prostatic hyperplasia and to learn whether the outcome can be varied by changing the cost or effectiveness of the alternatives. DESIGN: The study is made by a decision tree in order to test the cost-effectiveness (CE) rate of three treatment strategies: a) watchful waiting; if there is no response a drug is administered and if there is no response transurethral resection of the prostate (TURP) is done, b) pharmacological treatment, and if there is no response TURP is done, and c) to apply TURP initially. The treatment is simulated taking 1000 patients with MBPH and testing the outcome of events and probabilities in a two-year treatment and from the point of view of the health system as services supplier. MEASUREMENTS AND RESULTS: Effectiveness is obtained from an american experts' consensus. Only the direct fangible costs are taken into account, in constant 1998 pts. An univariant simple sensitivity analysis is made considering the cost variables of TURP and from the drugs in an acceptable range of +/- 20%, and the effectiveness of the watchful waiting and the pharmacological treatment. The lower cost alternative per improved patient (IP) is the watchful waiting (77,069 pts./IP) followed by the drug treatment (118,656 pts./IP) and lastly the TURP (456,642 pts./IP). Variations in the variable values make no difference in the relative positions of the tested alternatives. CONCLUSIONS: From the pharmacoeconomics point of view the MBPH treatment must be iniciated by watchful waiting, proceeding to drug administration only if there is a positive response and to make use of TURP when the pharmacological procedures have not been effective.

Cost-Benefit Analysis↗

Phytotherapy in the treatment of benign prostatic hyperplasia.

There are numerous plant extracts that have been used for the treatment of benign prostatic hyperplasia and lower urinary tract symptoms. While some extracts show promise, their efficacy has not been adequately proven in long-term, double-blind placebo-controlled trials monitored by an outside agency.

Drug Therapy, Combination↗