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Osteopontin expression in prostate cancer and benign prostatic hyperplasia.

OBJECTIVES: Osteopontin (OPN), a secreted adhesive glycoprotein, has been shown to be produced in excessive amounts in a variety of experimental models of malignancy. Increased levels of OPN exist in blood from the lungs, breasts, and gastrointestinal tracts of cancer patients with metastases. However, there have been no reports on the expression of OPN in human urological malignancies. The present study investigates the presence of OPN in adenocarcinoma of the human prostate and in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Using prostate tissue from 34 patients with primary prostate cancer, 13 patients with prostate cancer after having undergone hormonal therapy, and 12 patients with BPH, formalin-fixed paraffin sections were prepared. Specimens were obtained by needle biopsy or radical prostatectomy. Immunohistochemical staining (ABC method) was then performed. Staining was divided into either negative or positive categories. RESULTS: Positive staining of OPN was observed on cancer cells and macrophages in 52.9% of the primary prostate cancers and 14.5% of the prostate cancers after hormonal therapy. In BPH specimens, 66.7% of the cases displayed positive staining of OPN. The staining level of OPN showed no correlation with serum prostate-specific antigen, but did correlate with stage, differentiation, and Gleason's score. CONCLUSIONS: The result postulates that the expression of OPN is an indicator of cell differentiation; however, it cannot be used as a marker of malignancy in prostate cancer.

Adenocarcinoma↗

Magnetic resonance imaging and morphometric histologic analysis of prostate tissue composition in predicting the clinical outcome of terazosin therapy in benign prostatic hyperplasia.

PURPOSE: To determine whether magnetic resonance imaging (MRI) or quantitative color-imaged morphometric analysis (MA) of the prostate gland are related to the clinical response to terazosin. METHODS: Thirty-six male patients with symptomatic benign prostatic hyperplasia (BPH) with a serum prostate-specific antigen level of 4-10 ng/mL underwent MRI with body coil, transrectal prostate ultrasonography and biopsy prior to terazosin therapy. For MRI-determined stromal and non-stromal BPH, the ratio of the signal intensity of the inner gland to the obturator internus muscle was evaluated. Histologic sections were stained with hematoxylin and eosin. The MA of the specimens was performed by Samba 2000. Results of the two techniques were interpreted according to the terazosin therapy results. RESULTS: The mean stromal percentage was 60.5 +/- 18.0%. No statistically significant relationship was found between the clinical outcome of terazosin and the MRI findings. The MA results showed a significant relationship between the percentage of stroma and the percent change of the peak urinary flow rate, but not with the percent change of the international prostate symptom score after terazosin therapy (P < 0.05). CONCLUSION: Magnetic resonance imaging alone is not sufficient in predicting the response to terazosin therapy. Morphometric analysis of BPH tissue composition can be used in predicting the clinical outcome of terazosin therapy but it is suitable only in patients for whom prostatic biopsy is necessary in order to rule out prostate cancer.

Adrenergic alpha-Antagonists↗

Histopathologic characterization of hereditary benign prostatic hyperplasia.

OBJECTIVES: Recent studies suggest the presence of a hereditary form of benign prostatic hyperplasia (H-BPH). This study was undertaken to characterize the histopathologic features of BPH in these men. METHODS: Because study subjects with H-BPH were young (mean age 59 years) and had a large prostate (mean prostate weight 61 g), we compared the histopathologic findings in these men with those in two different control groups: (1) age-matched control subjects (mean age 59 years; mean prostate weight 31 g), and (2) prostate weight-matched control subjects (mean age 70 years; mean prostate weight 61 g). Using a color video image analysis system, we morphometrically determined stromal/epithelial ratios in histologic sections taken from 12 men with H-BPH, 36 age-matched control subjects, and 36 prostate weight-matched control subjects. RESULTS: The stromal/epithelial ratio was 2.6 +/- 1.4 in the men with H-BPH, 2.7 +/- 1.7 in the age-matched control subjects, and 1.7 +/- 0.9 in the prostate weight-matched control subjects. Regression analysis, which controlled for the differences in prostate weight or patient age between men with H-BPH and age-matched and prostate weight-matched control subjects, respectively, revealed a significant difference between men with H-BPH and prostate weight-matched control subjects (P = 0.015) but no difference from age-matched control subjects (P = 0.36). CONCLUSIONS: The larger prostates in young men with H-BPH are characterized by a higher stromal/epithelial ratio than are similar-sized prostates in older men with sporadic BPH. This finding gives rise to speculation that H-BPH is associated with an increase in stromal elements.

Adult↗

[Diagnostic scale of infravesical obstruction in patients d with benign prostatic hyperplasia].

A clinical diagnostic scale of infravesical obstruction (IVO) in patients with benign prostatic hyperplasia is proposed which provides the diagnosis of IVO in BPH patients with probability up to 89% basing only on clinical evidence obtained at a detailed urological examination (size of the gland, size and index of the prostatic transitional zone, residual urine, micturition urine, maximal micturition rate).

Humans↗

Transforming growth factor-beta induces growth inhibition and IGF-binding protein-3 production in prostatic stromal cells: abnormalities in cells cultured from benign prostatic hyperplasia tissues.

The IGF axis has been implicated in the pathogenesis of benign prostatic hyperplasia (BPH) via the paracrine action of IGFs and IGF-binding proteins (IGFBPs). In this study, we examined the regulation of cell growth and IGFBP-3 secretion by transforming growth factor-beta (TGF-beta) in prostatic stromal cell (PC-S) cultures from histologically normal tissues and tissues from BPH. PC-S cultures were treated with varying doses of TGF-beta1. Forty-eight hour conditioned media (CM) from these cultures were subjected to Western immunoblotting and ligand blotting for detection and quantification of IGFBPs. IGFBPs-2, -3 and -4 were detected in the CM from normal PC-S cultures. In CM from BPH PC-S, IGFBP-3 levels were 2-fold lower at baseline than in the normal PC-S CM, in addition to the differences in IGFBPs-2 and -5 which we have previously reported. In response to TGF-beta1, a 15-fold increase in the levels of IGFBP-3 was observed in normal PC-S CM, while a mere 2-fold increase was observed in BPH PC-S CM (P<0.001). These findings were confirmed by specific immunoblotting and immunocytochemistry. IGFBP-3 mRNA levels detected by Northern blotting of total RNA extracted from similar cultures showed the induction of IGFBP-3 expression by TGF-beta1 in normal PC-S and its lack of induction in BPH PC-S. Cell growth inhibition in response to TGF-beta1 correlated with the IGFBP-3 concentrations found in CM. Normal PC-S showed a 60% decrease in cell number after 10 days in media with 1 ng/ml TGF-beta1, compared with the untreated control. The decrease in proliferation observed in comparably treated BPH cells was only 20% (P<0.001). In conclusion, BPH PC-S had a reduced IGFBP-3 response to TGF-beta1 and demonstrated decreased TGF-beta1-induced growth inhibition relative to normal PC-S. We hypothesize that in normal PC-S, TGF-beta exerts its anti-proliferative effects by stimulating the production of IGFBP-3, which acts as an inhibitory factor, either by inhibiting IGFs or directly by interacting with cells, and that this process is altered in BPH PC-S.

Blotting, Western↗

[The use of serpens for treating patients with benign prostatic hyperplasia].

320 mg of serpense was given daily to 24 patients with benign prostatic hyperplasia (BPH) for 2 months. Control check-ups were performed each 30 days. The effect was judged by the patient's condition (I-PSS), quality of life, residual urine, the gland size, urodynamic picture and level of prostatic specific antigen (PSA). The response of BPH to serpense was noticeable, especially at the first stage of the disease (66.7%). Reduced serum PSA in serpense-treated patients may be explained by peripheral selective inhibition of 5 alpha-reductase or, rather, by anti-inflammatory action of the drug. Antidropsical and antiinflammatory actions of serpense suggest its possible efficacy in chronic prostatitis.

Aged↗

The clinical uroselectivity of alfuzosin is not significantly affected by the age of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: To assess the effect of the age of patients with benign prostatic hyperplasia (BPH) on the clinical uroselectivity of alfuzosin during general medical practice. PATIENTS AND METHODS: The present national, multicentre, open-labelled, observational study involved 4018 Spanish outpatients with BPH, i.e. showing lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction. The patients received sustained release (SR) alfuzosin, 5 mg twice daily, for 2 months. The primary efficacy criteria were symptomatic improvements, as assessed by the International Prostate Symptom Score (IPSS) and quality of life (QoL) index. Safety was assessed by monitoring cardiovascular data and adverse events. RESULTS: The patients were divided into four age groups, i.e. < 56, 56-65, 66-75 and > 75 years. All groups of patients showed a mean IPSS decrease of 11-12 (55.8-65.4% from baseline) at the end of the study, while the QoL decreased by 2-3 points (55.6-63.6% from baseline). There were no relevant effects of age on the efficacy of the treatment. Moreover, alfuzosin was well tolerated independently of the age of the patient; 1.2% of the patients enrolled withdrew because of adverse events. The qualitative distribution of vasodilatory/nonvasodilatory adverse events was similar in all age groups. The incidence of asymptomatic orthostatic hypotension was low (0.58%) and not affected by the age of the patients. CONCLUSION: This study confirms that the clinical uro-selectivity of SR-alfuzosin, already described in ran-domized controlled studies, is not significantly affected in clinical practice by the age of the patients. This is considered particularly relevant to the characteristics of patients with BPH, as they are mostly elderly men.

Adrenergic alpha-Antagonists↗

[Shape memory alloy spiral for urethrostenosis caused by benign prostatic hyperplasia].

The nitinol (shape memory alloy, SMA) spiral was used in 39 patients with benign prostatic hyperplasia (BPH). Caine experiment indicated that the spiral could be embedded by prostatic urethra epithelium in 6 months. The new transitional epithelium between spiral wires was originated from the urethra transitional epithelium as proved by immunohistochemical staining. The parts of spiral project over the bladder cavity formed incrustation on the spiral tip. The nitinol is of super-elastic property, corrosive-resistance and excellent biocompatibility, in addition to unique shape memory effect. We treated 39 patients with BPH by self-made coaxial sheath introducing Chinese nitinol spiral into the prostatic urethra, with a successful rate of 89.7%. Follow-up for 3-26 months showed no incrustation and migration of the spiral.

Aged↗

"BPSA," a specific molecular form of free prostate-specific antigen, is found predominantly in the transition zone of patients with nodular benign prostatic hyperplasia.

OBJECTIVES: The biologic mechanism for the increased proportion of noncomplexed ("free") prostate-specific antigen (PSA) found in the serum of patients with benign prostate disease is unknown. We recently reported that most of the PSA found in benign, hyperplastic, and cancerous prostatic tissue is in the free form. To determine whether specific molecular forms of free PSA are associated differentially with normal, hyperplastic, or cancerous prostatic tissue, we have further characterized the free PSA in each type of prostatic tissue. METHODS: PSA was purified by immunoaffinity chromatography from matched prostatic tissue samples of peripheral zone cancer (PZ-C), PZ noncancer (PZ-N), and transition zone (TZ) tissue from 10 large-volume (greater than 50 g) and 8 small-volume (less than 25 g) radical prostatectomy specimens. Eight TZ specimens obtained during transurethral resection of the prostate for benign prostatic hyperplasia (BPH) were also analyzed. The different molecular forms of PSA were further resolved by high-performance hydrophobic interaction chromatography. Clipped forms of PSA were identified by N-terminal amino acid sequencing. RESULTS: More than 99% of the PSA in prostatic tissues was in the free, noncomplexed form. Specimens from the prostate TZ were found to contain elevated levels of an altered form of PSA, which we designated BPSA. Purified BPSA contained a distinctive cleavage at lysine 182. The median percent BPSA (%BPSA) was 11.4 in the TZ of specimens with nodular BPH compared with a %BPSA of 4.1 in the TZ of specimens without nodular BPH (P <0.0014). The median %BPSA levels of the PZ-N and PZ-C tissues ranged from 3.2 to 4.9 and were not significantly different from one another or from the %BPSA level of TZ tissues without nodular BPH. CONCLUSIONS: We have identified a specific molecular form of clipped free PSA, called BPSA, that is increased within the prostatic TZ of patients exhibiting nodular BPH. Higher levels of percent free PSA in serum have been found to correlate strongly with prostate volume, which in turn is closely associated with the progressive enlargement of nodular BPH tissue within the TZ of the prostate. Thus, it is possible that a proportion of the serum percent free PSA found in patients with BPH may be composed of BPSA released into the serum.

Humans↗

Importance of prostatic sonography in the evaluation of conservative therapy of prostatic hyperplasia.

Drug therapy using an alpha-reductase inhibitor is being conducted in 23 patients with benign prostatic hyperplasia (BPH), hopefully resulting in a decrease in prostatic volume. Suprapubic ultrasonography determination of prostatic size has proven to be a reliable parameter of the disease course. In 142 evaluated ultrasonic measurements, a maximum deviation of +/- 7% for the diameter and +/- 13% for the volume was established. Therefore a change in volume after drug therapy of BPH can only be considered significant if a decrease in volume is 15% or more.

5-alpha Reductase Inhibitors↗

Age-related changes of histological composition in established benign prostatic hyperplasia.

To clarify the effect of aging on the histological composition of established benign prostatic hyperplasia (BPH), quantitative morphometric analyses were performed. Specimens were obtained from 23 patients who underwent transurethral resection of the prostate due to symptomatic BPH. Smooth muscle cells, fibrous tissue, glandular cells, glandular lumen and vascular tissue were quantified. Stromal and glandular components of established BPH did not correlate with age, whereas the proportion of vascular tissue was inversely correlated with age (r = -0.572, p = 0.0046). In the present series, the main characteristic of BPH tissue of elderly men appeared to be decreased vascularity.

Aged↗

Genetic susceptibility of benign prostatic hyperplasia.

In an effort to provide new insight into the etiology of benign prostatic hyperplasia (BPH), an evaluation of genetic factors was performed. Recognizing that early age of onset is a marker for hereditary disease, we performed a case-control study of men with early onset of significant BPH. Men in the youngest quartile (less than 64 years old) with a large prostate (greater than 37 gm. resected tissue) who underwent surgery for BPH were identified as case probands from 909 consecutive prostatectomies for BPH. Control probands, selected because of the ability to distinguish treatment for benign prostate disease from treatment for malignant prostate disease, were women whose spouses underwent radical prostatectomy during the same interval. Male relatives of men with early onset of BPH had a 66% cumulative lifetime risk of prostatectomy for BPH, compared to a 17% cumulative risk among control relatives (p = 0.001). A 4-fold increase in age-specific risk of prostatectomy for BPH was present among relatives of men who had undergone prostatectomy for BPH (p = 0.0003), while brothers of these affected cases had a 6-fold increase in risk (p = 0.0089) compared to controls. To determine the likelihood that genetic factors account for this familial aggregation of BPH, segregation analysis was done. Although the small sample size prevented rigorous exclusion of nongenetic models, direct comparison of mendelian and nongenetic models showed that mendelian transmission provided the best overall explanation of the observed familial aggregation. The optimal model suggested mendelian dominant inheritance of a gene associated with early age at onset of BPH. These findings identify family history of BPH as a risk factor for clinical BPH and suggest the presence of a predisposing gene in patients with early onset BPH. Evidence of dominant mendelian transmission of this allele provides a framework for genetic studies to characterize this gene and elucidate the development of BPH in general.

Aged↗

[Observation of the therapeutic effect of qianlie sanyu capsule on benign prostatic hyperplasia].

OBJECTIVE: To observe the clinical efficacy of Qianlie Sanyu Capsule on benign prostatic hyperplasia (BPH). METHODS: Seventy-two patients with BPH were randomly divided into a treatment group (40 patients) and a control group (32 patients), the former treated by Qianlie Sanyu Capsule and the latter by Longbishu. Observation were made on the changes of the patients' urination' symptoms, living quality, prostatic volume, Qmax uroflowmetry and excel urine before and after treatment. RESULTS: The total efficacy rates were 92.5% in the treatment group, and 72.5% in the control group. Comparison between the two groups showed significant difference (P < 0.01). The urination symptoms, living quality, Qmax uroflowmetry and the excel urine were better improved in the Qianlie Sanyu group than in the Longbishu. There were significant differences between the two groups (P < 0.05), but none in reducing effect on the prostatic volume. CONCLUSION: Qianlie Sanyu Capsule is an effective drug for BPH.

Capsules↗

Relationship among symptom score, prostate volume, and urinary flow rates in 543 patients with and without benign prostatic hyperplasia.

BACKGROUND: Studies on the relationship among symptom score, urinary flow rate, and prostate volume in men with lower urinary tract symptoms (LUTS) continue to be of great interest. METHODS: A total of 2,418 men, aged 30-86 years, agreed to participate in an interview and to complete a questionnaire regarding voiding patterns. All subjects answering positively to one or more of the questions were submitted to a diagnostic assessment, based on the algorithm outlined by the guidelines of the International Consultation on Benign Prostatic Hyperplasia (BPH). Five hundred forty-three out of the 2,418 participants (22.45%) were evaluated. At the end of the diagnostic evaluation, 400 men with LUTS but without concomitant conditions (except BPH) known to interfere with normal voiding were selected. Descriptive statistics were used to characterize age, symptom score (International Prostate Symptom Score), prostate volume, and urinary flow rate distribution in these patients. Correlations among the aforementioned parameters were evaluated by means of a multivariate, multiple linear regression and logistic regression model. RESULTS: As reported in other studies, only weak or modest correlations were found. Moreover, the 400 cases were classified according to four age decades. The decrease in peak and mean flow rate per decade of age was similar (0.5 and 0.4 ml/sec); the increase in prostate volume and in total symptom score per decade was 3.3 cc and 0.6, respectively. In patients less than 50 years old, most of the correlations were stronger than those observed in the entire population of 400 men (age and prostate volume, c.c. 0.2864; age and peak flow rate, c.c. -0.2689; age and mean flow rate, c.c. -0.3034). However, symptom score continued to be weakly correlated with age and prostate volume (c.c. 0.0498 and 0.1966, respectively). In the last part of the study, men were assigned to different treatment strategies. Patients who were assigned to surgical treatment had higher prostate volume and IPSS and lower urinary flow rate than those assigned to nonsurgical treatment. CONCLUSIONS: We believe that the reason for the weak statistical association frequently reported in the literature is mainly the urology clinic-based population from which the patient samples were drawn. Data emerging from this analysis support the hypothesis that age is one of the principal factors influencing the relationship among symptom score, urinary flow rate, and prostate volume.

Adult↗

Serum prostate specific antigen levels during hyperthermia treatment of benign prostatic hyperplasia.

To understand better the tissue and cell changes occurring in the human prostate as a reaction to heat, we used circulating prostate specific antigen as a marker to detect cell injury. The prostate in 18 patients with benign prostatic hyperplasia was heated to 42 +/- 1.5C with local microwaves at 915 MHz. Each treatment sessions lasted 1 hour and the patients underwent 5 treatment sessions. A total of 90 treatment sessions was performed among 18 patients. No significant difference was observed between pre-treatment and post-treatment serum prostate specific antigen levels. We conclude that local hyperthermia is an atraumatic treatment modality that does not exert its effect on the hyperplastic prostate via a cytotoxic insult to prostate epithelial tissues.

Antigens, Neoplasm↗

Transurethral microwave thermotherapy: the gold standard for minimally invasive therapies for patients with benign prostatic hyperplasia?

From all available minimally invasive methods for the treatment of symptomatic benign prostatic hyperplasia (BPH), transurethral microwave thermotherapy (TUMT) has gained a firm position as the most attractive option. Recent research has produced innovations in high-energy TUMT, including new treatment protocols, refined selection criteria, and monitoring of intraprostatic temperature. Furthermore, long-term results from randomized studies comparing TUMT with transurethral resection of the prostate (TURP) or medical treatment are now available. All these data indicate that more durable clinical outcomes and less morbidity can be achieved with TUMT, strengthening its position as a standard treatment for BPH. This paper describes the status of TUMT in the treatment of lower urinary tract symptoms related to BPH, focusing on variations in the outcomes with different devices, the durability of treatment outcomes, morbidity, selection criteria, and cost. The relation of TUMT to medical management and TURP also is addressed.

Cost-Benefit Analysis↗