Treatment Of Benign Prostatic Hypertrophy Research Articles

Molecular Stating of Prostate Cancer. II. A Comparison of the Application of an Enhanced Reverse Transcriptase Polymerase Chain Reaction Assay for Prostate Specific Antigen Versus Prostate Specific Membrane Antigen

Current imaging modalities used to stage prostate cancer clinically fail to detect extracapsular disease in a significant subset of patients. A molecular based peripheral blood assay using the reverse transcriptase polymerase chain reaction has recently been shown to be a highly sensitive staging modality for detecting extraprostatic disease preoperatively. The assay uses primers that are specific for prostate specific antigen (PSA). We compare the application of the reverse transcriptase polymerase chain reaction assay using primers specific for the human prostate specific membrane antigen with results obtained from the same specimens by reverse transcriptase polymerase chain reaction for PSA. Prostate specific membrane antigen, a recently cloned prostatic antigen, is a transmembrane glycoprotein that has been described as prostate specific. These assays were applied to ribonucleic acids extracted from the peripheral blood lymphocyte fraction of 80 patients with clinically localized prostate cancer. In addition, blood specimens from 20 female patients, 20 young male patients, 25 age-matched control men under treatment for benign prostatic hypertrophy and 20 men with established, untreated metastatic prostate cancer were tested. All 3 groups of noncancer patients had negative polymerase chain reactions for PSA as well as prostate specific membrane antigen. Of 20 metastatic prostate cancer patients 16 (80 percent) had positive polymerase chain reactions for PSA, while only 10 (50 percent) had positive results for prostate specific membrane antigen. Among the 80 patients with clinically localized disease (stages T1 to T2cNOMO), 27 and 19 had positive polymerase chain reaction for PSA and prostate specific membrane antigen, respectively, from blood specimens obtained preoperatively. Analyzing the final pathology in each patient with the reverse transcriptase polymerase chain reaction assay identified a significantly stronger correlation with tumor invasion using the results of the PSA test rather than the results of the prostate specific membrane antigen reverse transcriptase polymerase chain reaction test (67 percent versus 34 percent sensitivity for detecting capsular penetration, 87 percent versus 46 percent sensitivity for detecting disease to the surgical margin and 83 percent versus 16 percent sensitivity for detecting seminal vesicle invasion). In contrast to the reverse transcriptase polymerase chain reaction assay for PSA, a similar assay done for prostate specific membrane antigen did not correlate with pathological stage of prostate cancer.

Drug treatment of benign prostatic hypertrophy

Benign symptomatic prostatic hypertrophy will affect up to 25% of men. Transurethral resection of

Estimation of urethral resistance by curve fitting in the pressure-flow plot. Theory and experience in normal men and men with benign prostatic hypertrophy.

The curvature of the urethral resistance relation was estimated in 21 normal men, in 32 prostatism patients, in 60 men with a diagnosis of benign prostatic hypertrophy (BPH) and obstruction, and in 55 men after treatment of BPH. The curvature was determined by curve fitting in the pressure-flow plot using the method of least squares. In all, 58% of the normal men and prostatism patients had a urethral resistance relation with the convexity directed upward, demonstrating a low-compliant type of distensibility. After transurethral resection (TUR), significantly more men had the convexity of the urethral resistance relation directed downward, showing that the distensibility was more of a constrictive type. This change in the elastic properties of the flow-controlling zone can be assessed only by using several curvatures to estimate the urethral resistance relation. Another advantage for the method of using different curvatures is that the effects of bladder contractility are minimized. However, should one use only one form of the urethral resistance relation, it is recommended that a linear relation be chosen.

Current treatment of BPH

Benign prostatic hypertrophy (BPH) is one of the most common diseases of adult males which increases with age. Effective therapeutic agents are an attractive option for patients for whom surgery is not a necessity, improving quality of life when compared with watchful waiting. Epidemiological studies show that 88% of patients over 80 years of age present anatomical BPH. This prevalence is similar in male populations throughout the world. Surgical treatment (transurethral resection of the prostate: TURP) has been the gold standard for over 50 years in patients with an enlarged prostate and obstructive symptoms but 20% of patients remain unsatisfied with surgery. Various medicinal preparations have been used since biblical times, in particular plant extracts which are still prescribed in Europe. Some claim to have an enzymatic inhibitory effect, but currently have not demonstrated objective efficacy. Alpha-blockers act on bladder and prostate smooth muscle, the contraction of which is mediated through alpha 1-receptors. Treatment has shown increased uroflow, decreased residual volume and a decrease in symptoms of BPH. Alpha-blockers; however, have shown no effect on prostate volume nor a reduction in the need for surgery for these patients. Finasteride, currently the only 5 alpha-reductase inhibitor approved for treatment of symptomatic BPH, has been widely investigated. The drug has been shown to decrease prostate volume, improve symptoms, uroflow and invasive urodynamic parameters in the majority of patients. Dihydrotestosterone (DHT) is decreased but the level of serum testosterone is maintained. Prostatic specific antigen is decreased by 50% as an effect of the drug on epithelial cells. Overall, the drug is well tolerated but some patients have shown decreased libido and/or impotency; however, two-thirds of these patients improved when the treatment was continued. Two effective medical therapies are currently available for treating symptomatic BPH: finasteride and alpha antagonists. Studies are now in progress to determine whether a combination of these therapies would be an effective alternative to surgery or watchful waiting.

Prostate irradiation as an alternative to the conventional management of benign prostatic hypertrophy

AbstractTo help determine the efficacy of radiation therapy (RT) as an alternative to conventional treatment of benign prostatic hypertrophy (BPH), seven patients were treated at Hahnemann University Hospital (Philadelphia, PA), between November 1981 and May 1988, with megavoltage RT for BPH. Indications for treatment included severely symptomatic disease while having medical contraindications to, or refusal of conventional treatments. Doses ranged from 2,000 to 2,400 cGy, using 300–400 cGy fractions twice per week for 2.5–3 weeks. Radiation was delivered using 6 MV photons. All patients experienced good relief of both irritative and obstructive symptoms. Six of seven patients remained free of recurrent symptoms. There were no short‐ or long‐term complications. These preliminary data suggest that there may be a future role for RT in the treatment of BPH in the medically inoperable patient. However, further study is needed before this can be seriously considered a standard treatment alternative. © 1995 Wiley‐Liss, Inc.

Use of recombinant α1-adrenoceptors to characterize subtype selectivity of drugs for the treatment of prostatic hypertrophy

Several α 1-adrenoceptor antagonists have recently been developed for the treatment of benign prostatic hypertrophy because of their less frequent systemic side-effects compared to conventional α 1-adrenoceptor blockers. One potential explanation for their good tolerability would be the selectivity for a certain subtype of α 1-adrenoceptor. Utilizing COS-7 cells expressing the rat α 1A, the hamster α 1B and the human α 1C-adrenoceptors, we investigated affinities of alfuzosin, doxazisin, terazosin, indoramin and (+)- and (−)-5-[2-[[2-(o-ethoxyphenoxy)ethyl] amino]propyl]-2-methoxybenzesulfonamide HCl (YM 617) compared to prazosin. Radioligand binding studies showed that the affinities of α 1-adrenoceptor subtypes for alfuzosin (K 1 value; α 1A: 2.4 nM, α 1B: 1.4 nM, α 1C: 4.2 nM), doxazosin (K i value; α 1A: 2.7 nM, α 1B: 3.2 nM, α 1C: 7.5 nM), terazosin (K i value; α 1A: 2.5 nM, α 1B: 2.7 nM, α 1C: 7.1 nM), indoramin (K i value; α 1A: 69 nM, α 1B: 21 nM, α 1C: 13 nM) and prazosin (K i value; α 1A: 0.16 nM, α 1B: 0.19 nM, α 1C: 0.2 nM) were equipotent to the three receptor subtypes. Unlike these antagonists, both (+)- and (−)-YM617 had relatively lower affinity for α 1B receptors compared to the other subtypes ( K i value; for (+)-YM617, α 1A: 22 nM, α 1B: 96 nM, α 1C: 4.3 nM; for (−)-YM617, α 1A: 0.11 nM, α 1B: 0.7 nM, α 1C: 0.035 nM). The data suggest that α 1-adrenoceptor antagonists currently used for the treatment of the benign prostatic hyperplasia do not show substantial subtype selectivity.

Long-term probability of prostatism vs general morbidity and mortality. Prospectively obtained data in a randomly selected cohort aged > 50 years.

In a 7-year study of 178 randomly selected healthy men older than 50, data were respectively obtained concerning treatment for benign prostatic hypertrophy (BPH) and overall morbidity and mortality. Plain symptom scores were calculated in all cases and urinary voiding was recorded in 112. The maximum flow rate was read and the pattern of flow curve determined. Log rank test and survival curves were used in evaluation of results. The general risk of death or disease overshadowing BPH greatly exceeded the probability of surgery for prostatism. The only factor predicting need for prostatectomy was a symptom score higher than 6 points. If the symptom score is low and indications for treatment are otherwise, relative, an expectant attitude to surgery for BPH is advocated.

A critical overview on the role of the Nd:YAG laser in the treatment of benign prostatic hypertrophy.

A critical overview on the role of the Nd:YAG laser in the treatment of benign prostatic hypertrophy.

TRANSRECTAL LOW LEVEL LASER THERAPY IN THE MANAGEMENT OF PROSTATIC PROBLEMS:

A pilot study is presented on the transrectal application of helium neon (HeNe) laser energy (20 mW, c/w) via a specially-designed probe for the treatment of chronic prostatitis in a patient population of 235. Laser therapy was administered at doses of from 11.5∼14.4 J per 12∼15 minute daily session, with 8∼12 sessions required. Results were graded as: good (complaints relieved, ultrasound assessment, uroflowmetry and speed of micturation normal, and semen tests showed no inflammation); satisfactory (complaints reduced with partial improvements as above); and negative (little or no change). 70.2% were graded good, 20.9% as satisfactory and 21% as negative. The same system was also applied in the treatment of benign prostatic hypertrophy (BPH), in a patient population of 167 (69 BPH I and 98 BPH II). 12∼15 daily sessions of 20 min were required, with doses of 19.0∼20.8 J per session. With the same grading criteria as for the prostatitis group, results were good in 14.4%, satisfactory in 42.5% and negative in 43.1%. An additional group of 13 patients with prostatodynia received 5∼6 daily sessions of from 8 to 10 minutes, average dosage of 8.8 J/session. All 13 patients were graded good. All patients in the three groups had received conventional medical therapies, some over a period of years, but without effect. Although there was no attempt at double blinding in the present study, the author suggests that the positive results should encourage such a double blind trial to be set up, and that HeNe low level laser therapy (LLLT) applied transrectally is a valid alternative or adjunctive therapy for the minimally invasive and painless treatment of prostatic problems.

Prostate-specific antigen and androgen deprivation therapy.

Prostate-specific antigen (PSA) is a kallikrein-like serine protease that, for all practical purposes, is specific for prostatic tissue. PSA is usually detected at low concentrations (0.0-4.0 ng/ml) in the serum and is the most important tumor marker for detecting otherwise unsuspected prostate cancer; it also useful for monitoring the response of prostate cancer to various types of therapy. Androgen deprivation therapy (ADT) includes bilateral orchiectomy, luteinizing hormone-releasing hormone (LHRH) agonists, antiandrogens, and 5-alpha-reductase inhibitors. Treatment of benign prostatic hypertrophy (BPH) or prostate cancer with ADT usually decreases the serum PSA concentration. Recent basic science research has demonstrated that the expression of the PSA gene is controlled by androgens acting via the androgen receptor. Therefore, in some patients a low serum PSA concentration will be the result of hormonal down-regulation of the genetic expression of PSA and not the result of the antitumorigenic activity of the therapy. Nevertheless, in spite of the direct effect of ADT on PSA expression, PSA remains a valuable prostate cancer tumor marker for prognosticating the response to ADT and portending clinical progression after this type of treatment for most patients.

?1-adrenoceptor subtype affinities of drugs for the treatment of prostatic hypertrophy

We have used radioligand binding and inositol phosphate accumulation studies to determine the affinity at mixed alpha 1A- and alpha 1B-adrenoceptors (rat cerebral cortex and kidney), alpha 1A-adrenoceptors (rat cerebral cortex and kidney following inactivation of alpha 1B-adrenoceptors by chloroethylclonidine treatment) and alpha 1B-adrenoceptors (rat spleen) for drugs currently under investigation for the treatment of benign prostatic hypertrophy, alfuzosin, naftopidil and (-)- and (+)-tamsulosin. Alfuzosin and naftopidil had similar affinities in all model systems (approximately 10 nM and 130 nM, respectively) and lacked relevant selectivity for alpha 1-adrenoceptor subtypes. Their potency to inhibit noradrenaline-stimulated inositol phosphate formation in cerebral cortex matched their affinities as determined in the binding studies. Tamsulosin had higher affinity at alpha 1A- than at alpha 1B-adrenoceptors, and was slightly more potent than alfuzosin and naftopidil at alpha 1B- and considerably more potent at alpha 1A-adrenoceptors. However, the interaction of the tamsulosin isomers with chloroethylclonidine-insensitive (alpha 1A-like) adrenoceptors was complex. A detailed analysis of the tamsulosin data and those obtained with other drugs, most notably noradrenaline and oxymetazoline, suggested that chloroethylclonidine-insensitive alpha 1-adrenoceptors may be heterogeneous and that this heterogeneity may differ between cerebral cortex and kidney of the rat.

Alfuzosin, a selective alpha 1-adrenoceptor antagonist in the lower urinary tract.

1. Phenylephrine-induced contractions of rabbit isolated trigone and urethra were antagonized in a competitive manner by alfuzosin (pA2 7.44 and 7.30, respectively) and prazosin. 2. The characteristics of [3H]-prazosin binding to human prostatic adenoma tissue were evaluated. [3H]-prazosin was potently displaced by alpha 1-adrenoceptor specific agents including alfuzosin, its (+)- and (-)-enantiomers and prazosin (IC50 0.035, 0.023, 0.019 and 0.004 microM, respectively), but only weakly by alpha 2-adrenoceptor selective agents, for example, yohimbine (IC50 = 6.0 microM). 3. In the pithed rat, alfuzosin (0.03-0.3 mg kg-1, i.v.) markedly inhibited pressor responses produced by the alpha 1-selective agonist, cirazoline but inhibited only slightly responses to the alpha 2-selective agonist, UK 14,304. Alfuzosin (1 mg kg-1, i.v.) had minimal effects against responses mediated by stimulation of prejunctional alpha 2-receptors (UK 14,304-induced inhibition of sympathetic tachycardia). 4. In the anaesthetized cat, alfuzosin (0.001-1 mg kg-1, i.v.) and prazosin (0.001-0.3 mg kg-1, i.v.) produced dose-related inhibition of the increases in urethral pressure caused by stimulation of sympathetic hypogastric nerves. Prazosin was approximately 5 fold more potent than alfuzosin. When phenylephrine was employed to induce urethral and vascular alpha 1-mediated tone simultaneously, prazosin inhibited both stimuli with similar potency whereas alfusozin was 3-5 fold more potent against elevated urethral pressure. This functional uroselectivity of alfuzosin was more evident by the intraduodenal route, since doses of 0.03 and 0.1 mg kg-1 alfuzosin inhibited urethral pressure with minimal effects on arterial blood pressure. 5. Alfuzosin is a potent selective alpha1-adrenoceptor antagonist in tissues of the lower urinary tract including the human prostate. This provides a pharmacological basis for its use in the treatment of benign prostatic hypertrophy.

Transurethral balloon divulsion of prostate

Benign prostatic hypertrophy (BPH) is the most common cause of urinary outflow obstruction. Transurethral resection of the prostate (TURP) is the preferred treatment for symptomatic BPH and is considered the gold standard of treatment. Balloon dilatation of the prostate (TUBD), besides some criticism, represents a nonoperative treatment alternative for treatment of symptomatic BPH which is simple and safe. We describe the technique of TUBD, balloon technology, as well as advantages and disadvantages of balloon dilatation.

Case histories

Two groups of patients have been chosen from our operating case histories (April '89 - December '91). They were subjected respectively to major and minor surgery. In the first group radical surgery of the kidney and of the bladder was considered while in the second group we examined the surgical and endoscopic treatment of benign prostatic hypertrophy. The selected patients were subsequently subdivided according to age (under and above 75 years old) and according to the kind of operation.

Transurethral Microwave Thermotherapy for Prostatism: Early Mayo Foundation Experience

As part of a multicenter investigative trial, transurethral microwave thermotherapy of the prostate was used in 60 men with symptomatic benign prostatic hypertrophy. A single office treatment on the Prostatron, a device that provides concurrent microwave heating of the prostate and conductive cooling of the urethra, was well tolerated and caused no major adverse events. Symptomatic improvement, especially the decrease in nocturia and urgency, was dramatic, and urinary flow was improved at 6 weeks. Continued follow-up suggests that further improvement will be achieved and that transurethral microwave thermotherapy has a role in the treatment of benign prostatic hypertrophy.

Reoperation and mortality after surgical treatment of benign prostatic hypertrophy in a large prepaid medical care program.

The incidence of reoperation and mortality after prostatectomy was studied in 8,219 men who underwent surgical treatment for benign prostatic hypertrophy between 1976 and 1987 while they were members of the Kaiser Permanente Medical Care Program, Northern California Region. The vast majority (94.5%) received transurethral prostatectomy (TURP). The cumulative 8-year probability of a second prostatectomy was 7.6% after TURP and 2.1% after open prostatectomy. The risk of mortality associated with transurethral prostatectomy relative to open prostatectomy was 1.6 (95% confidence interval 1.2, 2.1) 8 years postsurgery. The increased risk of mortality associated with transurethral prostatectomy was most prominent during the first 5 years postsurgery (relative risk 1.8, 95% confidence interval 1.3, 2.5) and declined to 1.1 (95% confidence interval 0.8, 1.6) for deaths occurring after the first 5 years. The finding of an increased risk of mortality associated with transurethral prostatectomy is consistent with other studies and is unexplained.

Nd:YAG laser ablation of the prostate as a treatment for benign prostatic hypertrophy.

Many techniques have been used to relieve obstructive symptoms associated with benign prostatic hypertrophy. Transurethral resection of the prostate (TURP) with an electrocautery loop is the most commonly performed operation to relieve bladder neck and urethral obstruction caused by prostatic adenoma. There is increased interest in alternative therapies to reduce prostatic size for symptom relief in this condition. We describe a technique using the neodymium:YAG (Nd:YAG) laser and a 600-microns laser quartz fibre with an attached terminal gold-plated metal alloy reflector to provide reliable deep penetration into prostatic tissue for prostatic adenoma ablation. We report the first use of this technique in three patients with benign prostatic obstruction and one with localised adenocarcinoma of the prostate.

Late Complications of Prostakath Treatment for Benign Prostatic Hypertrophy

The self-retaining intra-urethral device "Prostakath" was inserted in a consecutive series of 29 men with obstructive benign prostatic hypertrophy. Fifteen patients were relieved of prostatic symptoms for an observation period of 22 weeks (range 2-60). The spiral was removed in 14 cases (48%) at an average of 14 weeks (range 1-82) after insertion; in 9 patients this was because of urinary retention and in 5 it followed dislocation of the stent into the bladder. Five stents removed after 44 weeks of treatment (range 21-82) were severely calcified. Light microscopic investigation of the Spirals that were removed revealed no damage to the gold-plated surface. All patients with calcification had chronic urinary infection resistant to antibiotic treatment. We believe that infected urine is the major factor responsible for the calcification. We suggest that patients with recurrent urinary infection after insertion of the Prostakath should be closely followed up and checked for stone formation by a plain X-ray of the bladder region. It may be advisable to change the Prostakath in patients with resistant urinary tract infection at 6-monthly intervals.

Alfuzosin for treatment of benign prostatic hypertrophy

To assess the long-term efficacy and safety of alfuzosin, a selective alpha 1-adrenergic antagonist, 518 symptomatic patients with benign prostatic hypertrophy (BPH) were randomised to received either alfuzosin (daily dose 7.5-10 mg) or placebo for 6 months. Obstructive and irritative symptoms, assessed according to the Boyarsky scale, significantly improved in the alfuzosin group compared with the placebo group (p = 0.0004). Fewer patients in the alfuzosin group than in the placebo group dropped out due to lack of efficacy (6.8% vs 14.6%, p = 0.004) and the prevalence of spontaneous acute urine retention was lower in the alfuzosin group (0.4% vs 2.6%, p = 0.04). By 6 months, mean urinary flow rates had increased (p less than 0.05) and residual volume had decreased (p = 0.017) in the alfuzosin group, although the two groups were broadly similar with respect to increase in peak flow rate. The overall incidence of adverse events was similar in the two groups, which led to the withdrawal of 10.8% and 9.0% of patients, respectively. The findings emphasise the magnitude of the placebo response in symptomatic patients with BPH and show that treatment with alpha 1 adrenergic antagonist drugs provides long-lasting improvement in such patients.

Balloon dilatation of the prostate as compared with transurethral resection of the prostate for treatment of benign prostatic hypertrophy

Balloon dilatation of the prostate is gaining widespread recognition and usage. This study compares the effectiveness in the production of symptomatic relief by balloon dilatation performed in 53 patients with that produced by transurethral prostatectomy (TURP) concurrently performed in 43 patients. Based on previously defined selection criteria, 64% of the dilated patients achieved a successful outcome (>50% reduction in symptoms) if they met the exclusion criteria, but only 31% who failed to meet the criteria achieved such success. By the same definition TURP was successful in 79% of our patients, and in that group the average weight of resected tissue was 35 g. In the remaining 21% of our subjects who did not achieve success following TURP, the average weight of resected tissue was 7 g. The results support the conclusion that balloon dilatation may be effective in treating symptomatic men with small prostate glands, whereas TURP is most effective in treating those with large prostates.