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Identification of genes differentially expressed in benign prostatic hyperplasia.

Differences between benign prostatic hyperplasia (BPH) and normal prostate tissue at the level of mRNA expression provide an opportunity to identify candidate genes for this disease. A cDNA subtraction procedure was used to isolate differentially expressed genes in BPH. The subtraction was done by solution hybridization of BPH cDNA against excess normal prostate cDNA. We identified known, EST, and novel genes by sequence and database analysis of the subtracted cDNAs. Several of these cDNAs were used as probes in Northern blotting analysis to confirm over-expression of their corresponding mRNAs in BPH tissues. One highly upregulated sequence of interest shared identity with a known mRNA encoding human NELL2, a protein containing epidermal growth factor-like domains. NELL2 was not previously reported to be expressed in prostate and may code for a novel prostatic growth factor. In situ hybridization analysis of hyperplastic prostate specimens demonstrated that NELL2 mRNA expression is predominantly localized in basal cells of the epithelium. Disease-related changes in the levels of NELL2 may contribute to alterations in epithelial-stromal homeostasis in BPH. (J Histochem Cytochem 49:669-670, 2001)

Blotting, Northern↗

Newly developed transurethral radiofrequency thermotherapy device for benign prostatic hyperplasia: a pilot study in canine prostate.

The safety and efficacy of transurethral microwave thermo-therapy (TUMT) for the treatment of symptomatic benign prostatic hyperplasia (BPH) have been demonstrated in the urological literature. Since a radiofrequency electromagnetic wave has deeper and more even transmission of heat to tissues than a microwave, we have developed a new prototype device for transurethral thermotherapy using a radiofrequency electromagnetic wave. The device consists of a microcomputer-controlled heat generator operating at 8 Mhz, a temperature monitoring system, a urethral cooling system and a urethral applicator and a rectal thermosensor probe. A balloon electrode encased in a specialized Foley catheter is connected parallel to twin plate electrodes on both sides of the pelvic region. An 8-MHz electromagnetic wave is directed to the prostate by means of capacitive coupling. The water coolant continuously perfused through the catheter allows high temperatures within the prostate while preserving the urethral mucosa. Heating experiment using agar phantom showed the hot spots to be distributed at 0.5-3 cm from the catheter surface. Heating experiment using canine prostates demonstrated that an intraprostatic temperature of > 48 degrees C could be achieved while the urethral and rectal temperatures had not exceeded 36 and 40 degrees C respectively. Histological examination immediately after the experiment showed the urethral mucosa to be preserved while coagulation necrosis of the periurethral prostate accompanied with congestion and hemorrhage of small blood vessels were observed at 5-8 mm from the urethra. The bladder and the rectum showed no gross alterations. Histopathological examination 10 days after the experiment revealed the intact urethral mucosa and mild mononuclear infiltration around the destroyed periurethral glands.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Serum prostate-specific antigen discriminates weakly between men with benign prostatic hyperplasia and patients with organ-confined prostate cancer.

To determine if serum prostate-specific antigen (PSA) can identify those patients harboring an organ-confined prostate cancer prior to treatment for symptomatic benign prostatic hyperplasia (BPH), we examined retrospectively the preoperative serum PSA level for two groups of men. Group 1 consisted of 187 consecutive patients with a histologic diagnosis of BPH as determined from complete pathologic analysis of the transurethral resection of the prostate (TURP) specimen. Group 2 included 198 consecutive patients with histologically confirmed organ-confined prostate cancer as determined from step-section analysis of the retropubic radical prostatectomy specimen. The median serum PSA value for group 1 was 3.9 ng/ml (range 0.2-55 ng/ml), whereas the median serum PSA level for group 2 was 5.9 ng/ml (range 0.4-58 ng/ml). Although this difference was statistically significant (p < 0.001), the distribution of serum PSA values for group 1 overlapped considerably with the distribution for group 2. For both groups, there was a clustering of PSA values below 10.0 ng/ml (group 1: 90%; group 2: 73%). The area under the receiver operating characteristic curve for log PSA values to discriminate men with BPH from patients with organ-confined prostate cancer was 0.66 (95% confidence interval: 0.60-0.72); a 'perfect' test has an area of 1.0, whereas a test with 'no information value' has an area of 0.5. These findings suggest that serum PSA has only a modest ability to distinguish men with BPH from patients with organ-confined prostate cancer. As a result, some symptomatic BPH patients choosing a non-TURP therapy may harbor a clinically significant prostate cancer despite being evaluated with a serum PSA determination.

Aged↗

Effect of D-004, a lipid extract from the Cuban royal palm fruit, on atypical prostate hyperplasia induced by phenylephrine in rats.

BACKGROUND AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Saw palmetto (Serenoa repens), the dwarf American palm (Arecaceae family), is commonly used to treat BPH. The Cuban royal palm (Roystonea regia) also belongs to the Arecaceae family, and 200-400mg of D-004, a lipid extract from its fruits, administered orally for 14 days has been shown to prevent testosterone- but not dihydrotestosterone-induced prostatic hyperplasia in rats. D-004 (125-250 microg/mL) added to preparations of rat vas deferens caused a marked, dose-dependent and significant inhibition of noradrenaline-induced smooth muscle contraction, a response mediated through alpha(1)-adrenoceptors, and was more effective in these respects than Saw palmetto. However, the in vivo effects of D-004 and Saw palmetto on the hypertensive response induced by noradrenaline were modest (albeit significant), and neither treatment affected resting blood pressure or heart rate in rats. The differential effects of D-004 in in vitro and in vivo models could be related to a differential affinity for adrenoceptor subtypes or to different bioavailabilities in vascular and urogenital targets. Phenylephrine injected into rodents induces prostatic hyperplasia with all the characteristic morphological changes of the condition but does not result in enlargement of the prostate. Therefore, this phenylephrine-induced change in rat prostate tissue is called atypical prostatic hyperplasia. It serves as an in vivo model of prostatic hyperplasia induced by stimulation of alpha(1)-adrenoceptors. The objective of this study was to determine whether D-004 can inhibit induction of atypical prostatic hyperplasia by phenylephrine in rats. METHODS: Rats were randomly distributed into five groups (ten rats/group). One group was a negative control and received oral vehicle only. The other four groups were injected subcutaneously with phenylephrine (2 mg/kg): of these groups, one was a positive control receiving the vehicle, and the other three groups were treated with D-004 or Saw palmetto (both 400 mg/kg) or tamsulosin 0.4 mg/kg. All active treatments were given orally for 28 days. After completion of treatment, rats were placed unrestrained in metabolic cages and micturition studies were performed. The rats were later killed and their prostates removed and weighed. Prostate samples were processed for histological study, with histological changes being assessed according to a scoring system. Bodyweight was measured at baseline and at weekly intervals. RESULTS: Histological examination of positive control rats revealed features of atypical prostatic hyperplasia, with piling-up, papillary and cribiform patterns and budding-out of epithelial cells. Micturition assessment revealed that phenylephrine significantly lowered both the total volume of urine in 1 hour and the volume per micturition; the latter was considered the main efficacy variable. D-004 and Saw palmetto extracts significantly prevented this reduction in volume per micturition by 70.5% and 68.6%, respectively, while tamsulosin totally abolished the reduction in micturition induced by phenylephrine (100% inhibition). Tamsulosin, D-004 and Saw palmetto significantly reduced the histological changes of atypical prostatic hyperplasia induced by phenylephrine by 73.1%, 61.2% and 50.0%, respectively. CONCLUSIONS: Administration of D-004 resulted in marked and significant prevention of phenylephrine-induced impairment of micturition and histological changes in rat prostate. These findings indicate that, in vivo, D-004 effectively opposes these responses to phenylephrine, which are mediated through urogenital alpha(1)-adrenoceptors. In this respect, D-004 was moderately more effective than Saw palmetto, a phytotherapeutic standard used to treat BPH, but less effective than tamsulosin, a selective alpha(1A)-adrenoceptor antagonist.

Animals↗

Stromal cells from human benign prostate hyperplasia produce a growth-inhibitory factor for LNCaP prostate cancer cells, identified as interleukin-6.

To understand specific interactions between stromal cells and epithelial cells in benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma, we developed stromal-cell cultures from normal human prostate (PNX) and BPH (BH101), composed of fibroblasts and myofibroblasts. Their role in epithelial-cell growth was studied using the established cancer cell lines LNCaP, PC3 and DU145 and an SV40 large T-immortalized normal epithelial-cell line, PNT1A, in double-diffusion co-culture chambers. PNT1A was stimulated by PNX (x1.6) and more strongly by BH101 stromal cells (x2.7). Conversely, LNCaP growth decreased by 50% in the presence of BH101 stromal cells (stromal/epithelial ratio: 10). A BH101-conditioned medium (CM), obtained in serum-free conditions, induced 90% inhibition of [3H]thymidine incorporation of the LNCaP androgen-sensitive cell line. Two other androgen-independent prostate cancer cell lines were either insensitive to BH101 CM (PC3) or slightly inhibited (40% for DU145). BH101 produced large amounts of IL-1beta, IL-6 and IL-8. HPLC gel filtration enabled separation of an inhibitory fraction which contained IL-6. IL-6 was demonstrated to be responsible for the strong inhibitory effect since an IL-6-neutralizing antibody abolished this inhibition, which was reproduced by human recombinant IL-6. Recombinant IL-6 growth inhibition was observed only on LNCaP prostate cancer androgen-sensitive cells.

Adult↗

The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group.

BACKGROUND: Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction. METHODS: In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period. RESULTS: As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups. CONCLUSIONS: The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

5-alpha Reductase Inhibitors↗

Therapeutic effect of D-004, a lipid extract from Roystonea regia fruits, on prostate hyperplasia induced in rats.

Benign prostatic hyperplasia (BPH) is a nonmalignant growth of prostate leading to difficulty in urinating. Drug therapy, phytotherapy included, is frequently used to treat BPH. D-004 is a lipid extract from Roystonea regia fruits, and previous studies have shown that oral treatment with D-004 for 14 days prevented prostate hyperplasia (PH) induced by testosterone in rats. No information is available, however; about the effects of D-004 in reverting already established PH. This study investigated whether D-004 could improve PH after oral dosing with testosterone in rats. Rats were distributed in five groups (10 rats/group). One group was injected with soy oil (negative control) and four groups were injected with testosterone: one was orally treated with the vehicle (positive control), two with D-004 (200 and 400 mg/kg) and the other with Saw palmetto (400 mg/kg). At study completion, the rats were sacrificed and the prostates were removed and weighed. D-004 (200 and 400 mg/kg) significantly and dose-dependently decreased prostate enlargement by 85% and 98%, respectively, versus the positive control. Likewise, Saw palmetto (400 mg/kg) significantly reduced prostate weight by 73% versus the positive control. D-004 (400 mg/kg) was more effective (p < 0.05) than Saw palmetto (400 mg/kg) in lowering prostate enlargement. D-004 and Saw palmetto also decreased the prostate weight to body weight ratio, but did not affect body weight. In conclusion, D-004 (200 and 400 mg/kg) orally administered was effective for reducing PH after testosterone dosing. D-004 (400 mg/kg) was more effective than Saw palmetto (400 mg/kg). Further studies, however, are needed to corroborate the present results.

Animals↗

[Medical treatment of benign prostatic hyperplasia. The efficacy of finasteride depends on prostatic volume].

OBJECTIVE: To demonstrate that the efficacy of finasteride in benign prostatic hyperplasia (BPH) depends on the prostate volume. METHODS: 75 patients with BPH were classified according to the prostate volume: 20-40 Gm (group I), 40-80 Gm (group II) and more than 80 Gm (group III). The average duration of treatment for all three groups was 16.2 months. Patients were evaluated for symptom score (I-PSS), quality of life, prostate volume by ultrasound, maximum urinary flow rate, residual urine, plasma PSA and testosterone levels. RESULTS: Ultrasound demonstrated a reduction in prostatic volume of 6.8-14.8 Gm. Symptom score was reduced by 9.2-15.5 points and quality of life 2-2.7 points. Maximum urinary flow rate increased 3.4-4.4 ml/sec and residual urine decreased in all three groups. Testosterone values showed no significant changes. PSA values showed a reduction of 1.3-1.7 ng/ml. CONCLUSIONS: The efficacy of finasteride depends on the prostatic volume. Medical treatment is a temporary alternative to surgery due to its cost and because patients are unaccustomed to having to take a tablet daily.

Enzyme Inhibitors↗

Medical management of benign prostatic hyperplasia: a review.

Benign prostatic hyperplasia (BPH) is a common disease affecting elderly men with 70% of men over 70 years showing microscopic evidence of hyperplasia. Transurethral resection of the prostate is the gold standard treatment. Medical management of BPH has involved the use of plant extracts, amino acids, kampo and animal organ preparations in various countries with unsatisfactory results. The use of alpha adrenergic antagonists dates back twenty years representing a major breakthrough in the treatment by relaxation of the dynamic contraction of smooth muscle component of prostatic obstruction. The evolution of alpha antagonist therapy resulted in clinical trials with selective antagonists such as prazosin, alfuzosin, indoramin, terazosin and doxazosin all of which achieve similar effective relief of obstructive symptoms as phenoxybenzamine, but with fewer side effects related to postural hypotension. 5-alpha reductase inhibitors, finasteride and episteride, recently synthesised act on the static component of obstruction caused by the enlarging prostate. They inhibit conversion of testosterone to the potent intracellular androgen dihydrotestosterone (DHT) resulting in the reduction of prostate volume and improvement of obstructive symptoms. Clinical trials with finasteride for three years indicate that 63% of patients had a reduction of greater than 20% in prostatic volume and 42% had a decrease of greater than 30% with a mean increase peak flow rate of 2.4 mls/s equivalent, to 20 years reversal of disease progression.

Adrenergic alpha-Antagonists↗

Immunolocalization of oestrogen and progesterone receptors in prostatic hyperplasia and carcinoma.

Oestrogen receptors and progesterone receptors were immunolocalized in 19 patients with benign prostatic hyperplasia and in 26 patients with prostatic carcinoma. Immunohistochemistry was performed on tissue that had been fixed in 8% paraformaldehyde and then paraffin-embedded, using microwave irradiation for antigen retrieval. Oestrogen receptor expression was observed exclusively in the stromal cells of six out of 26 (23%) patients with prostatic carcinoma, but in none of the cells of patients with benign prostatic hyperplasia. Progesterone receptor expression was detected in 16 of 19 (84%) and 17 of 19 (89%) of the epithelial cells and stromal cells of patients with benign prostatic hyperplasia, respectively. In patients with prostatic carcinoma, progesterone receptor immunoreactivity was observed in 12 of 20 (46%) and 20 of 26 (77%) of the carcinoma and stromal cells of prostatic carcinoma, respectively. The ratio of epithelial cells with progesterone receptor immunoreactivity corresponded well with that of stromal cells with immunoreactivity in patients with benign prostatic hyperplasia. However, the ratio of stromal cells with progesterone receptor immunoreactivity was much higher than that in carcinoma cells in patients with prostatic carcinoma. Immunolocalization patterns or the ratio of the cells with progesterone receptor immunoreactivity did not significantly correlate with histological differentiation or patient's age in carcinoma cases. However, patients with advanced surgical stages of disease demonstrated a significantly smaller number of carcinoma and stromal cells with progesterone immunoreactivity in patients with prostatic carcinoma. These results suggest that oestrogens do not have a direct effect on the biological behaviour of benign prostatic hyperplasia and prostatic carcinoma, but that progesterone appears to play a role in the pathogenesis of benign prostatic hyperplasia and prostatic carcinoma.

Aged↗

Ultrastructural and biophysical studies on protein conformations of epithelium and stroma in benign prostatic hyperplasia before and after transurethral resection of the prostate.

The alterations in protein conformation of epithelium and stroma in human benign prostatic hyperplasia (BPH) undergoing prostatic needle biopsy (PNB) and transurethral resection of the prostate (TURP) were isolated in vitro and investigated using attenuated total reflectance (ATR)/Fourier transform infrared (FT-IR) microspectroscopy. Second-derivative spectral analysis and a curve-fitting program were used to verify and obtain the protein secondary conformation and composition of the samples. TURP uses an electric cutting heat but PNB is a nonheating process. The results indicate a predominantly higher proportion of beta-sheet conformation of the epithelium or stroma in BPH tissue at 1633 or 1630 cm(-1) in the amide I band, but after treatment with TURP, both maximum peaks shifted to 1644 or 1646 cm(-1) due to random coil structure, respectively. This conversion suggests that the heat generated by the cutting loop could increase the temperature in the tissue surrounding the prostate, thereby modifying the protein conformational structure of epithelium and stroma in BPH tissue.

Aged↗

Rapid proliferation of prostatic epithelial cells in spontaneously hypertensive rats: a model of spontaneous hypertension and prostate hyperplasia.

Spontaneously hypertensive rats (SHRs), a commonly used model of genetic hypertension, exhibit features of glandular hyperplasia of the ventral prostate, including the narrowing of acini with epithelial protrusions into the lumen and the piling up of epithelial cells. These rats also have frequent urinary voiding. In order to define the fundamental processes that lead to prostatic hyperplasia in SHRs, we compared the proliferation rate of their prostatic epithelial cells (PECs) in primary culture and in vivo to that of Wistar-Kyoto rats (WKYs), their normotensive controls. In vitro, primary cultures of SHR PECs had a shorter doubling time than those of WKY (3.3 vs 8.0 days) and showed higher levels of bromodeoxyuridine (BrdU) incorporation into DNA. In vivo, the BrdU incorporation seen 48 hours following injection was observed primarily in areas of epithelial piling up, which are seen in SHRs but not in WKYs. We concluded that prostate hyperplasia in SHRs results from a genuine increase in the proliferation rate of PECs and that this rapid proliferation is a fundamental feature of SHR PECs, maintained both in vivo and in vitro. Thus, SHRs can serve as a model for glandular hyperplasia of the prostate, resulting from a genetic tendency for an increased rate of cell proliferation.

Animals↗

Prostatic stents for the treatment of benign prostatic hyperplasia.

PURPOSE OF REVIEW: The insertion of prostatic stents in the treatment of lower urinary tract symptoms in men secondary to benign prostatic obstruction from benign prostatic hyperplasia has proven to be an effective modality in properly selected patients. We review the current literature on the role of prostatic stents in the treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia. RECENT FINDINGS: Permanent stents such as the Urolume and the Memokath offer efficacious and safe treatment alternatives for men with bladder outlet obstruction from benign prostatic hyperplasia who are deemed high surgical risks for traditional transurethral resection of the prostate. When removal of permanent prostatic stent is necessary, the design of the Memokath allows for an easier removal than that of the Urolume. Temporary stents are being investigated as a means to treat the transient bladder outlet obstruction frequently observed after minimally invasive thermotherapy procedures aimed at treating benign prostatic obstruction, with both biodegradable and retrievable stents shown as successful modalities for this indication. SUMMARY: Prostatic stents remain an option to treat men with benign prostatic obstruction/bladder outlet obstruction; however, stent migration remains an obstacle to their widespread use. The key to obtaining optimal outcomes in men with benign prostatic hyperplasia is careful patient selection and experience with proper stent deployment.

Humans↗

[Study of patients with symptomatic benign prostatic hyperplasia who underwent transurethral resection of the prostate after ineffective alpha-1 blocker treatment by non-urologists].

We evaluated the clinical courses of 60 patients with symptomatic benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate (TUR-P) in our hospital after ineffective alpha-1 blocker treatment by non-urologists between January 2001 and September 2004. Overall severity just before TUR-P estimated by the criteria for severity in BPH was mild in 0%, moderate in 37%, and severe in 63%. Urinary retention was noted in 5 patients (8.3%). Nine patients (15.0%), four of whom had received an anti-cholinergic agent, had a residual urine volume over 200 ml. Excellent or good overall efficacy of TUR-P according to the criteria for efficacy of treatment in BPH was 86.7%. According to a questionnaire survey, only 28.9% of non-urologists in the Abashiri district had knowledge of the clinical practice guideline for BPH. We should strengthen the partnership among urologists and non-urologists to appropriately treat patients having BPH by using evidence-based information such as the clinical practice guideline.

Adrenergic alpha-Antagonists↗

Effect of baicalein on experimental prostatic hyperplasia in rats and mice.

We determined the effect of baicalein on prostatic hyperplasia in experimental animal models. Prostatic hyperplasia was induced by testosterone propionate in mice and castrated rats and by transplantation of homologous strain fetal mice urogenital sinus in mice. With the histopathological examination, the efficacy of baicalein on prostate hyperplasia in experimental animals was evaluated by the activity of serum acid phosphatase (ACP) and the following norm of the prostate gland: the volume, wet weight, wet weight index, dry weight index, DNA contents and prostatic epithelial height and cavity diameter. Results showed that baicalein at doses of 260 and 130 mg/kg administrated intragastrically (i.g.) significantly inhibited prostatic hyperplasia in castrated rats induced by testosterone propionate compared with the negative control group (p<0.01). Baicalein at doses of 520 and 260 mg/kg (i.g.) also significantly inhibited prostatic hyperplasia in mice induced by transplantation of homologous strain fetal mouse urogenital sinus and by testosterone propionate (p<0.01). These results suggested that baicalein has an inhibitory effect on prostatic hyperplasia in experimental animals.

Acid Phosphatase↗

Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia.

OBJECTIVES: To examine the rate of prostate cancer detection in three large randomized placebo-controlled benign prostatic hyperplasia trials of dutasteride. Dutasteride, which lowers serum dihydrotestosterone more than 93% by inhibiting type 1 and type 2 5-alpha-reductase, is effective in the treatment of benign prostatic hyperplasia. However, its effect on the development of prostate cancer is unknown. METHODS: A total of 4325 men with benign prostatic hyperplasia but without a history, or evidence, of prostate cancer, and a serum prostate-specific antigen level of 1.5 to 10 ng/mL, were randomized to 0.5 mg/day dutasteride or placebo for 24 months. The prostate cancer detection rates for subjects were determined by non-protocol-mandated biopsies, either during the double-blind phase of the study or during the first 3 months of the open-label extension. A follow-up questionnaire was administered to a subset of consenting subjects to ascertain the number, outcomes, and reasons for the prostate biopsies. RESULTS: The cumulative incidence of prostate cancer as an adverse event was significantly lower in the dutasteride versus placebo group at 24 months (1.1% versus 1.9%, P = 0.025) and 27 months (1.2% versus 2.5%, P = 0.002). There were no differences in the diagnosis rates of prostate cancer during the first 15 months, after which time the detection rate of prostate cancer increased in the placebo group and remained low in the dutasteride group. CONCLUSIONS: Prostate cancer detection was significantly lower in subjects randomized to dutasteride compared with the placebo group. These results have prompted the initiation of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study, which was designed and powered to test the hypothesis that treatment with dutasteride decreases the incidence and progression of prostate cancer.

5-alpha Reductase Inhibitors↗

Resistance to apoptosis and up regulation of Bcl-2 in benign prostatic hyperplasia after androgen deprivation.

PURPOSE: Benign prostatic hyperplasia (BPH) is related to advancing age and the presence of androgens and occurs in virtually all older men. BPH causes morbidity, most often by urinary obstruction, in a substantial fraction of men over sixty. Both finasteride and androgen ablation induce partial diminution in BPH that occurs over weeks to months. This is in contrast to the often rapid involution seen in both normal prostatic epithelium and prostatic carcinoma in response to androgen withdrawal. This study was performed to analyze the response of prostatic cells, and in particular BPH, to acute androgen ablation. MATERIALS AND METHODS: We subjected a cohort of 26 men to androgen ablation with goserelin, a gonadotrophin releasing hormone agonist, for 3-4 weeks prior to radical prostatectomy for prostate cancer. Preablation biopsy specimens and prostatectomy specimens were immunohistochemically stained for apoptotic cells and for expression of apoptosis regulatory proteins Bcl-2, Bax, Bcl-x, and Bak. RESULTS: Normal prostatic epithelial cells and prostate cancer responded to hormone deprivation by undergoing apoptosis, but in 19/26 specimens prostatic hyperplasia had a total absence of apoptosis. In all 26 specimens, benign prostatic hyperplasia demonstrated increased expression of the Bcl-2 protein, but no change in the expression of Bax, Bcl-x, and Bak. In contrast, adjacent normal and malignant prostatic epithelium showed positive staining for apoptosis and did not alter Bcl-2 expression in response to androgen ablation. CONCLUSIONS: BPH demonstrated increased staining for Bcl-2 after androgen deprivation that may render hyperplastic epithelium relatively resistant to apoptosis induced acutely by androgen withdrawal.

Apoptosis↗

Bipolar electrosurgery for benign prostatic hyperplasia: transurethral electrovaporization and resection of the prostate.

PURPOSE OF REVIEW: The gold standard for surgical treatment of benign prostatic hyperplasia continues to be transurethral resection of the prostate, which is traditionally performed using a monopolar electrocautery system resulting in the possibility of certain well-recognized complications. This has led to the development of alternative surgical procedures such as vaporization of the prostate and most recently use of bipolar systems. The advantages of bipolar electrosurgery include the ability to use isotonic saline during surgery, reduced blood loss and less heat damage to the surrounding tissue. We have reviewed some of the technical aspects of the bipolar systems as well as their clinical use. RECENT FINDINGS: Bipolar electrovaporization of the prostate (Gyrus Medical Ltd, Cardiff, Wales) has been established for a few years and some data are available suggesting that the system is safe and effective, at least in the short term. The new technique of bipolar transurethral resection of the prostate has been studied in a small number of studies with promising results. SUMMARY: Bipolar transurethral resection is a novel approach in treatment of the prostate. A real paucity of clinical data is seen regarding the outcomes with this form of surgery. Although the generator and the resecting loop are different to the monopolar system, the resection technique is very similar which may be attractive to practising urologists. The need for large multi-centre studies in effectiveness of bipolar transurethral resection of the prostate is apparent.

Clinical Trials as Topic↗