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PubMed2001

[Age-related changes in lower urinary tract symptoms and urodynamic parameters in patients with benign prostatic hyperplasia treated by transurethral resection of the prostate].

PURPOSE: To characterize age-related clinical and urodynamic features of patients with benign prostatic hyperplasia (BPH) treated by transurethral resection of the prostate (TUR-P). MATERIALS AND METHODS: Between July 1994 and March 2000, a total number of 451 patients underwent TUR-P in Nagoya Urology Hospital. Out of these 451 patients, 15 (3.3%) were diagnosed as having an incidental prostate cancer on pathological examination of resected prostate tissue. The remaining 436 patients (48-92 years, 69.8 +/- 7.4 years), in whom 196 (45.0%), 208 (47.7%) and 32 (7.3%) were < or = 69, 70-79 and > or = 80 years, respectively, were subjects for the present study. Their clinical features before and after TUR-P and the therapeutic effects of the treatment were evaluated in terms of aging. RESULTS: Among preoperative variables evaluated, IPSS in patients aged < or = 69 years was significantly higher than in those aged 70-79 years (p < 0.05). The QOL index was significantly higher in patients aged > or = 80 years than in those aged 70-79 years (p < 0.05). The maximum bladder capacity decreased with age from 276 ml in patients aged < or = 69 years to 211 ml in those aged > or = 80 years. Postoperatively, both maximum and mean flow rates were significantly lower in patients aged 70-79 and > or = 80 years compared to those aged < or = 69 years. There was, however, no significant age-related difference in IPSS and QOL index. The assessment of treatment effects at 3 months following TUR-P revealed that the outcomes in function as evaluated by uroflowmetry, anatomy and ultrasonic measurement of prostate volume were significantly worse in patients aged > or = 80 years compared to those in younger patients. However, there was no significant age-related difference in outcomes in subjective symptoms and QOL. CONCLUSIONS: TUR-P could be performed safely even in patients aged > or = 80 years. It is concluded that although postoperative urinary condition might be worse in older patients, they would nevertheless be satisfied with the results of TUR-P in the same way as less aged patients. As long as subjects are selected properly based on the correct diagnosis of BPH and a sufficient evaluation of operation risks, TUR-P can be expected to be performed safely and be followed by satisfaction with the treatment effects.

Aged↗
PubMed2006

Recovery of serum prostate specific antigen value after interruption of antiandrogen therapy with allylestrenol for benign prostatic hyperplasia.

Decrease in serum prostate specific antigen (PSA) concentration is inevitably associated with antiandrogen therapy for benign prostatic hyperplasia (BPH), and might mask the presence of prostate cancer or delay its diagnosis. To determine the appropriate timepoint for determination of correct PSA value, we sequentially measured serum PSA and testosterone levels after discontinuation of antiandrogen therapy for BPH. With informed consent, 12 patients (72.8 +/- 12.2* years old) with BPH were treated with allylestrenol 50 mg/day for 4 months. Serum testosterone and PSA concentrations were determined before and just after treatment, as well as every month after treatment up to 3 months. After treatment with allylestrenol for 4 months, mean serum testosterone and PSA levels were significantly decreased from 408 +/- 136* to 87.9 +/- 76.2* ng/dl, and from 2.81 +/- 0.87* to 2.04 +/- 0.82* ng/ml, respectively. The mean serum PSA level recovered to the pretreatment level within 2 months and mean serum testosterone concentration within one month after discontinuation of administration. In conclusion, during treatment of BPH with antiandrogen allylestrenol, a two-month washout is adequate for determination of correct PSA value (*: M +/- SD).

Allylestrenol↗
PubMed1994

Alpha-1 receptor mediated smooth muscle regulation in benign prostatic hyperplasia.

Symptoms in benign prostatic hyperplasia (BPH) are partially caused by an increased prostatic smooth muscle tone. This tone depends on extra- and intracellular Ca2+ stores and is regulated by various second messenger pathways. We investigated the role of intracellular Ca2+ stores and cyclic 3'-5' adenosine monophosphate (cAMP) in BPH. Contractions elicited by the specific alpha 1-receptor agonist phenylephrine (PE) were inhibited by the selective alpha 1-receptor antagonists prazosin and YM 617. To elucidate the contribution of intracellular Ca2+ stores to the alpha 1-receptor induced contraction nifedipine, a blocker of voltage dependent L-type Ca2+ channels (VDCC) was applied and found to inhibit the PE induced contractions up to 65%. To further confirm the participation of intracellular Ca2+ stores, we applied ryanodine (10 microM) which reduced the alpha 1-receptor mediated contractions up to 80%. The remaining contraction was sensitive to nifedipine. The cAMP pathway mediating smooth muscle relaxation by regulating intracellular Ca2+ concentrations ([Ca2+]i) was also investigated. Nonspecific phosphodiesterase (PDE) inhibitors such as papaverine (0.5 mM) and theophylline (1 mM) and the specific PDE inhibitor milrinone (0.5 mM), all of which prevent degradation of cAMP, suppressed the PE induced contractions by 82%, 91% and 68%, respectively. Forskolin (50 microM), an activator of adenylylecyclase (AC), inhibited the PE induced contractions by 83%. The membrane permeable cAMP analog, N6-2'-0-dibutyryladenosine derivative (dBcAMP) also reduced the PE induced response by 70%.

Adrenergic alpha-Antagonists↗
PubMed2002

[Dihydrotestosterone and the role of 5 alpha-reductase inhibitors in benign prostatic hyperplasia].

The genesis of benign prostate hyperplasia (BPH) depends on two factors: testicular androgen and the aging process. The most important androgen in the prostate is dihydrotestosterone (DHT). In the aging male the level of DHT in the prostate remains largely constant although the plasma level of testosterone decreases. DHT is formed by the reduction of testosterone by the enzyme 5-alpha-reductase, which has two isoenzymes. The 5-alpha-reductase type 2 is the predominant isoenzyme in genital tissue and thus also in the prostate. Finasteride is a 5-alpha-reductase inhibitor, which is applied in the treatment of BHP and male baldness. In the doses used finasteride acts mainly by inhibiting the 5-alpha-reductase type 2, thereby reducing the serum level of DHT by approximately 70% and by about 85-90% in the prostate. Indeed the effect of finasteride in BPH was proven in clinical studies. However, the circulating and intraprostatic DHT could be further reduced by a more effective dual 5-alpha-reductase inhibitor, which would be efficacious in the treatment of benign prostate hyperplasia and other DHT-related disorders.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1982

Proliferative responses of cultured rat prostate and human benign prostatic hyperplasia.

The proliferative responses of rat prostate and human benign prostatic hyperplasia have been followed in organ culture using [125I] iododeoxyuridine uptake to monitor DNA synthesis. In serum-free cultures, testosterone induced a marked increase in DNA synthesis (three-fold) in 4- to 6-month-old rat prostates at concentrations of 4 x 10(-9) to 4 x 10(-6) M, whereas in greater than 12-month-old rat prostates the response was less marked. Human benign prostatic hyperplasia also showed an increased uptake at similar testosterone concentrations and of a similar magnitude to the response of greater than 12-month-old rat prostates. At 10(-5) M DNA synthesis was markedly suppressed in cultures of both rat and human prostate. The proliferative response of human benign prostatic hyperplasia increases up to days 3 to 4 in culture and then declines in both control and hormone-treated groups and may represent repair processes which appear to be hormone dependent.

Animals↗
PubMed1993

Chromosome changes in benign prostatic hyperplasia and their significance in the origin of prostatic carcinoma.

Cytogenetic studies of benign prostatic hyperplasia (BHP) are scarce. We analyzed primary cell cultures obtained from biopsies of prostatic tissues from 10 patients (mean age: 60.7 years) with histologic diagnosis of BHP to compare the eventual chromosome changes with those reported in prostatic adenocarcinoma. Clonal chromosome abnormalities were noted in five of the 10 cases, with loss of Y chromosome in all. In one case, a clonal t(1;20) was observed with a -Y clone. Different numerical and structural sporadic abnormalities were evident in eight. Chromosome 1 was the chromosome most frequently involved in sporadic rearrangements. We concluded that -Y is a frequent nonrandom chromosome abnormality in BHP in this sample of patients. Immunohistochemical studies showed that loss of Y occurs in fibroblasts and not in epithelial cells; therefore, this anomaly is not related to cancer development.

Adenocarcinoma↗
PubMed1992

Relationship between prostatic acid phosphatase and prostate-specific antigen serum levels and prostatic volume in benign prostate hyperplasia. Pitfall on tumor markers assessment in primary prostatic cancer?

Serum levels of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were measured in 78 patients with benign prostate hyperplasia and compared with both the gland weight and the glandular component of prostatic tissue. Both PAP and PSA were significantly higher where prostate was heavier; however, we could not find a consistent factor which could correlate weight increase to marker levels. PSA tended to be higher when glandular component was more expressed. From the present findings we conclude that in patients with prostate cancer, PAP and PSA serum levels should be investigated considering also the benign components of prostate gland.

Acid Phosphatase↗
PubMed1988

Keratin patterns in prostatic hyperplasia and adenocarcinoma.

Keratin patterns in benign prostatic hyperplasia and prostatic adenocarcinoma were evaluated using frozen and formalin-fixed tissue. Five different commercially available antibodies were used. In frozen tissue basal cells of benign acinic and ductal structures stained with PKE, and to a lesser degree with MCA 144, CAM 5.2 and RCK 102. Luminal cells stained with MCA 144, CAM 5.2, RCK 102 and to a lesser degree with PKE. In formalin-fixed tissue basal cells stained exclusively with Z622, predominantly with PKE and RCK 102, and to lesser degree with MCA 144 and CAM 5.2. Luminal cells stained with MCA 144 and CAM 5.2 and to some degree with PKE and RCK 102, while Z622 stained luminal cells of ductal epithelium weakly, but acinic cells not at all. Luminal phenotype dominated in prostatic adenocarcinomas which were stained with MCA 144 and CAM 5.2 irrespective of differentiation, and independently of whether frozen or formalin-fixed tissue was used. However, the different keratin phenotype of benign and malignant prostatic epithelium depends to some degree on the immunohistochemical procedures used. In diagnostic pathology Z622 may be able to separate intraluminal neoplastic lesions from invasive carcinoma, a problem particularly seen when cribriform growth pattern is found.

Adenocarcinoma↗
PubMed1983

Lack of value of radioimmunoassay for prostatic acid phosphatase as a screening test for prostatic cancer in patients with obstructive prostatic hyperplasia.

We examined the incidence of prostatic cancer in patients with an elevated radioimmunoassay for prostatic acid phosphatase and clinical benign prostatic hyperplasia on digital rectal examination. Of 295 patients screened with prostatic acid phosphatase tests 17 fulfilled the criteria of having an elevated prostatic acid phosphatase, clinically benign prostate and histological examination of the prostatectomy specimen. None of the 17 patients had histological evidence of prostatic cancer. The results confirm the predictions of mathematical models that prostatic acid phosphatase is of no practical value as a screening test for prostatic cancer in patients with clinical benign prostatic hyperplasia.

Acid Phosphatase↗
PubMed2002

[Kampo preparations for prostatic hyperplasia: usefulness of Saireito for nocturia].

Prostatic hyperplasia is characterized by major voiding symptoms, and treatment aims principally at improving the quality of life. Nocturnal frequency is a primary symptom that markedly impairs the quality of life. In addition to alpha 1-receptor blockers and antiandrogen agents, herbal medicines and kampo preparations have also been used, but they have not always proved satisfactory. In this study, we investigated the effect of a diuretic kampo preparation (Kanebo Saireito Extract Fine Granules) on urine output, and evaluated the efficacy of Saireito (5.4 g/day, bid) in 12 patients (mean age, about 68) with prostatic hyperplasia who had completed basic therapy but still complained of nocturnal frequency. The following results were obtained. 1) Saireito caused a significant increase of daytime urine output and significantly reduced nocturnal output. 2) It significantly reduced the nocturnal frequency, although that of daytime urination remained unchanged. 3) The drug significantly improved symptoms that existed before treatment. These results suggest that Saireito is effective for nocturia in patients with prostatic hyperplasia.

Aged↗
PubMed1999

Medical management of benign prostatic hyperplasia.

The management of benign prostatic hyperplasia has undergone a rapid evolution over the past decade from a surgical emphasis to a medical emphasis. Great strides in the development of alpha-adrenergic blockers, 5 alpha-reductase inhibitors and a variety of phytotherapeutics have fueled this evolution. This article reviews the past, present and future of the medical management of benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗
PubMed1996

Symptomatic outcome of transurethral prostatectomy, alpha-blockade and placebo in the treatment of benign prostatic hyperplasia. Evaluation of treatment with the Danish Prostatic Symptom Score (DAN-PSS-1) system. The ALFECH Study Group.

To assess the symptomatic outcome following transurethral prostatectomy (TURP), alpha-blockade and placebo treatment in uncomplicated benign prostatic hyperplasia (BPH), 260 patients were evaluated with the recently formulated Danish Prostatic Symptom Score (DAN-PSS-1) system: 205 were randomized to either the selective alpha-blocker alfuzosin or placebo and 55 underwent TURP. Following TURP, the DAN-PSS-1 score was reduced by 80% after 6-10 weeks (visit 2) and by 100% after 12-16 weeks (visit 3). In the alfuzosin group the corresponding reductions were 40% and 65% (p < 0.02 vs. placebo). In the placebo group the reduction was 25% at visit 2, with no further fall demonstrated thereafter. During alfuzosin treatment the bother score (impact of symptoms on quality of life) fell more than the symptom score. During placebo treatment there was no reduction in symptom score. We conclude that the DAN-PSS-1 questionnaire sensitively identifies clinically important responses to treatment of BPH.

Adrenergic alpha-Antagonists↗
PubMed1984

The development of human benign prostatic hyperplasia with age.

In this study we report the prevalence and growth rate of human benign prostatic hyperplasia with age by combining and analyzing data from 10 independent studies containing more than 1,000 prostates. The normal prostate reaches 20 plus or minus 6 gm. in men between 21 and 30 years old, and this weight remains essentially constant with increasing age unless benign prostatic hyperplasia develops. The prevalence of pathological benign prostatic hyperplasia is only 8 per cent at the fourth decade; however, 50 per cent of the male population has pathological benign prostatic hyperplasia when they are 51 to 60 years old. The average weight of a prostate that is recognized at autopsy to contain benign prostatic hyperplasia is 33 plus or minus 16 gm. Only 4 per cent of the prostates in men more than 70 years old reach sizes greater than 100 gm. An analysis of a logistic growth curve of benign prostatic hyperplasia lesions removed at prostatectomy indicates that the growth of benign prostatic hyperplasia is initiated probably before the patient is 30 years old. The early phase of benign prostatic hyperplasia growth (men between 31 and 50 years old) is characterized by a doubling time for the tumor weight of 4.5 years. In the mid phase of benign prostatic hyperplasia growth (men between 51 and 70 years old) the doubling time is 10 years, and increases to more than 100 years in patients beyond 70 years old.

Adolescent↗
PubMed1989

[Cryosurgery in the treatment of prostatic hyperplasia].

Twenty five cases of prostatic hyperplasia were treated by blind and endoscopic cryoprostatectomy. 25 cases have been followed up for 3-12 months with a mean period of 9.2 months. The results of cryosurgery, in this series, turned out to be good in 15, effective in 8, and ineffective in 2 cases. The procedure is simple, safe and effective in the treatment of prostatic hyperplasia particularly for the high risk patients. The technique, indications, Immunity and complications of cryosurgery are discussed.

Aged↗
PubMed2001

[Mental disorders in patients with benign prostatic hyperplasia].

310 patients with benign prostatic hyperplasia have been studied. Their mental state being analyzed by clinical and psychometric methods using Spilberger and Hamilton scales. Neurotic disorders have been reported in all the patients: 53.8% having neurasthenic syndrome, 30% anxiety- or astheno-subdepressive syndrome, 16.2% neurotic hypochondriac symptomatology. After treatment with minor neuroleptics, antidepressants and tranquilizers, patients' psychic state improved, even when the objective urologic data remained unchanged. Treatment of mental disorders makes it possible to prepare a patient for the operation and to improve quality of life of patients with benign prostatic hyperplasia before the operation.

Aged↗
PubMed1999

The combination of human glandular kallikrein and free prostate-specific antigen (PSA) enhances discrimination between prostate cancer and benign prostatic hyperplasia in patients with moderately increased total PSA.

BACKGROUND: Prostate-specific antigen (PSA) is the most reliable tumor marker available and is widely used for the diagnosis and management of prostate cancer. Unfortunately, PSA cannot distinguish efficiently between benign and malignant disease of the prostate, especially within the range of 4-10 microg/L. Among the refinements developed to enhance PSA specificity is the free/total PSA ratio, which is useful in discriminating between the two diseases within the diagnostic "gray zone". Recent data indicate that human glandular kallikrein (hK2), a protein with high homology to PSA, may be an additional serum marker for the diagnosis and monitoring of prostate cancer. METHODS: We analyzed 206 serum samples (all before treatment was initiated) from men with histologically confirmed benign prostatic hyperplasia (n = 100) or prostatic carcinoma (n = 106) with total PSA in the range of 2.5-10 microg/L. Total and free PSA and hK2 were measured with noncompetitive immunological procedures. Statistical analysis was performed to investigate the potential utility of the various markers or their combinations in discriminating between benign prostatic hyperplasia and prostatic carcinoma. RESULTS: hK2 concentrations were not statistically different between the two groups of patients. There was a strong positive correlation between hK2 and free PSA in the whole patient population. hK2/free PSA ratio (area under the curve = 0.69) was stronger predictor of prostate cancer than the free/total PSA ratio (area under the curve = 0.64). At 95% specificity, the hK2/free PSA ratio identified 30% of patients with total PSA between 2.5-10 microg/L who had cancer. At 95% specificity, the hK2/free PSA ratio identified 25% of patients with total PSA between 2.5 and 4.5 microg/L who had cancer. CONCLUSIONS: Our data suggest that hK2 in combination with free and total PSA can enhance the biochemical detection of prostate cancer in patients with moderately increased total PSA concentrations. More specifically, the hK2/free PSA ratio appears to be valuable in identifying a subset of patients with total PSA between 2.5 and 4.5 microg/L who have high probability of cancer and who should be considered for biopsy.

Aged↗
PubMed2004

Preventive effects of D-004, a lipid extract from Cuban royal palm (Roystonea regia) fruits, on testosterone-induced prostate hyperplasia in intact and castrated rodents.

Benign prostatic hyperplasia (BPH) is the noncancerous, uncontrolled growth of prostate gland cells and stroma that can cause difficulty urinating. Fruit lipid extracts from saw palmetto, a palm from the Arecaceae family, are used for BPH management. The Cuban royal palm, Roystonea regia, is also a member of the Arecaceae family and therefore it was appropriate to investigate the protective effects of Roystonea regia fruit lipid extracts on prostatic hyperplasia. The aim of this study was to investigate whether D-004, a lipid extract from Roystonea regia fruits, prevented testosterone-induced PH in castrated and intact rodents. Two series of experiments were performed. The first one was conducted in castrated and intact rats, distributed into five groups of 10 rats per group. The negative control group was injected with soy oil and treated orally with vehicle, while the four testosterone-injected groups were treated with vehicle (positive control), D-004 100, 200 and 400 mg/kg, respectively. The other experiment was conducted in castrated and intact mice. These were distributed into four groups of 10 mice per group: a negative control group and three testosterone-injected groups, of which one was a positive control, while two received D-004 200 and 400 mg/kg, respectively. At study completion, the rodents were sacrificed and prostates removed and weighed. D-004 at doses of 100, 200 and 400 mg/kg significantly and dose-dependently prevented prostate enlargement in intact and castrated rats and mice. The percentage inhibitions obtained in mice were greater: 77% and 84% for intact and castrated mice, respectively. D-004 therapy did not affect body weight. It is concluded that D-004 administered orally significantly prevented testosterone-induced prostate enlargement in both intact and castrated rodents, indicating that an endogenous supply of testosterone is not necessary to observe such an effect The results of the present investigation support further studies of D-004 on experimental models of prostatic hyperplasia.

Animals↗
PubMed1999

Relation between urethral elasticity and bladder outlet obstruction and histologic composition of the prostate in patients with benign prostatic hyperplasia.

OBJECTIVES: In benign prostatic hyperplasia (BPH), bladder outlet obstruction is caused by mechanical blockage resulting from an enlarged prostate, and by the increased tone of prostatic smooth muscle. In patients with obstructive BPH, the prostatic urethra urodynamically corresponds to the flow-controlling zone (FCZ). We sought to investigate the relation between the obstruction and elastic properties of the FCZ and the histologic composition of the prostate in symptomatic patients with BPH. METHODS: The grade of infravesical obstruction was classified according to preoperative pressure-flow data from 30 men with symptomatic BPH, and the elastic properties of the FCZ were evaluated as the mean elastance, which was calculated using the three-parameter model. The area densities of smooth muscle, fibrous tissue, epithelium, and lumen were determined by quantitative morphometry, using BPH tissue obtained by transurethral resection. RESULTS: The area density of smooth muscle had a negative correlation with mean elastance (p = -0.50, P <0.01), the linear passive urethral resistance relation (p = -0.43, P <0.05), and the group-specific urethral resistance factor (p = -0.39, P <0.05). No other histologic element was correlated with these variables. CONCLUSIONS: Our results suggest that urethral elasticity and bladder outlet obstruction grade are influenced by the relative content of smooth muscle within the prostate in patients with BPH.

Aged↗