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Prostatic hyperplasia: an unknown feature of acromegaly.

This study was designed to investigate whether GH and insulin-like growth factor I (IGF-I) excess could lead to the development of benign prostatic hyperplasia and/or prostatic carcinoma. Prostatic diameters and volume as well as the occurrence of prostatic diseases were studied by ultrasonography in 10 untreated acromegalic patients less than 40 yr of age and 10 age- and body mass index-matched healthy males. Serum GH, IGF-I, PRL, testosterone, dihydrotestosterone, prostate-specific antigen, and prostatic acid phosphatase levels were assessed. All patients had secondary hypogonadism, as diagnosed by low testosterone levels, and 4 of 10 patients had hyperprolactinemia. After 1 yr of treatment with octreotide (0.3-0.6 mg/day), ultrasound scan and hormone parameters were repeated. The 4 hyperprolactinemic acromegalics were treated with octreotide and cabergoline (1-2 mg/week) to suppress PRL levels. Symptoms due to prostatic, seminal vesicle, and/or urethral disorders or obstruction were experienced by neither acromegalics nor controls. Digital rectal examination revealed no occurrence of prostatic nodules or other abnormalities. Compared to healthy subjects, a remarkable increase in transversal prostatic diameter and volume was observed in acromegalics. In healthy subjects, prostate volume ranged from 15.1-21.8 mL, whereas in acromegalics it ranged from 21.8-41.8 mL. Similarly, an increased median lobe was observed. In fact, the transitional zone diameter was just detectable in 5 of 10 controls, whereas it was measurable in all acromegalics (18 +/- 1.2 vs. 2.8 +/- 0.3 mm; P < 0.001). The prevalence of periurethral calcifications was more than doubled in acromegalics (50%) compared to that in controls (20%). Treatment with octreotide for 1 yr produced normalization of circulating GH and IGF-I levels in 7 of 10 patients. In these 7 patients, ultrasound evaluation showed a significant reduction of the antero-posterior diameter (26.1 +/- 1 vs. 28.9 +/- 1.6 mm; P < 0.01), the transversal diameter (44.9 +/- 2 vs. 48 +/- 2 mm; P < 0.01), and the cranio-caudal diameter (36.5 +/- 1 vs. 41.3 +/- 1.5 mm; P < 0.001), whereas the transitional zone diameter was unchanged (16.4 +/- 1.5 vs. 17.4 +/- 1.7 mm). As a consequence, a significant decrease in prostate volume was recorded (22.1 +/- 1.1 vs. 29.8 +/- 2.5 mL; P < 0.001). Prostate volume increased in 2 of the 3 patients who did not achieve normalization of GH and IGF-I after octreotide treatment. Finally, after treatment, serum testosterone levels were significantly increased (from 1.5 +/- 0.3 to 3.5 +/- 0.3 microg/L), whereas dihydrotestosterone, dehydroepiandrosterone sulfate, delta4-androstenedione, 17beta-estradiol, prostate-specific antigen, and prostatic acid phosphatase were unchanged. Serum PRL levels were suppressed after cabergoline treatment in all 4 hyperprolactinemic patients throughout the study period. In conclusion, prostate enlargement occurs in young acromegalics with a higher than expected prevalence of micro- and macrocalcifications. This suggests that a careful prostate screening should be included in the work-up and follow-up of acromegalic males.

Acromegaly↗

Prostatic tissual distribution of alfuzosin in patients with benign prostatic hyperplasia following repeated oral administration.

OBJECTIVES: The blood and prostatic concentrations of alfuzosin were determined in patients with benign prostatic hyperplasia (BPH). METHODS: 12 patients scheduled for BPH surgery were treated with alfuzosin 5 mg twice daily prior to surgery in an open trial. Seven doses were given over a 4-day period. Blood samples were drawn before the first and the last intake (day 3). On day 4 (surgery day), a blood and prostate tissue sample were taken simultaneously 12 hours after the last drug intake. RESULTS: Mean trough blood levels were 6.0+/-4.6 ng/ml and 5.8+/-3.7 ng/ml on day 3 and day 4, respectively, indicating a stable alfuzosin concentration. The mean prostate concentration on day 4 was 12.3+/-5.6 ng/g. Alfuzosin prostate and blood concentrations at 12 hours post dosing on day 4 were significantly correlated (r=0.804, p=0.0016); the prostate-blood ratio was 2.4+/-0.7. CONCLUSIONS: Oral administration of alfuzosin leads to a high diffusion of the drug into the prostate of BPH patients.

Administration, Oral↗

[The international system of overall scoring assessment of the symptoms and quality of life of patients with benign prostatic hyperplasia].

The paper presents the International system of overall score estimation of symptoms and life quality for patients with benign prostatic hyperplasia and reviews the results of this system application for objective diagnosis and evaluation of the efficacy of the treatment (chemotherapy, transurethral resection, transvesicular adenomectomy, transrectal hyperthermia, YAG-Nd laser prostatectomy) in 250 patients with benign prostatic hyperplasia. The fault of the system is the absence of specific recommendations for rating objective test results. The authors propose their variant of estimation of prostatic volume, maximal urination rate, residual urine.

Diagnosis, Differential↗

Serum human glandular kallikrein (hK2) and insulin-like growth factor 1 (IGF-1) improve the discrimination between prostate cancer and benign prostatic hyperplasia in combination with total and %free PSA.

BACKGROUND: There is growing evidence describing an association of hK2 and IGFs with cancer. The aim of this study is to investigate the differences in serum levels of hK2 and IGFs in a large group of patients with benign prostatic hyperplasia (BPH) or prostatic carcinoma (CaP) and to examine the value of these variables, as well as their various combinations with PSA, for discriminating between these two clinical entities. METHODS: Human glandular kallikrein 2 (hK2), insulin-like growth factor-1 (IGF-1), free and total PSA concentrations were measured with non-competitive immunological procedures. Receiver operating characteristic (ROC) analysis as well as univariate and multivariate logistic regression analysis were performed to investigate the potential utility of the various markers and their combinations for discriminating between BPH and CaP. RESULTS: hK2 and IGF-1 concentrations were increased in CaP patients, in comparison to BPH patients. hK2/free PSA and free/total PSA ratios (area under the curve, AUC = 0.70) were stronger predictors of prostate cancer than the IGF-1/total PSA ratio (AUC = 0.56) in the group of patients with total PSA <4 microg/L. The hK2/free PSA ratio (AUC = 0.74) was found to have significant discriminatory value in patients with total PSA within the "gray zone" (4-10 microg/L). Multivariate logistic regression models confirmed the observed relationships and identified IGF-1/free PSA and hK2/free PSA as independent predictors of CaP. CONCLUSIONS: hK2/free PSA and IGF-1/free PSA ratios may be useful adjuncts in improving patient selection for prostate biopsy.

Aged↗

[Experimental study of vasoligation in the treatment and prevention of benign prostatic hyperplasia].

OBJECTIVES: To investigate the possibility and efficacy of vasoligation and deferent vein ligation in treating and preventing benign prostatic hyperplasia(BPH). METHODS: 40 male pooches were divided into A, B, C and D groups randomly. Each group has 10 pooches group A and B were made into the model of BPH. Two years later, the pooches in group A and C accepted the operation of vasoligation and deferent vein ligation on both sides. Group B and D only accepted the operation of dissection and relieving its deferent duct. Then continuing to feed the 40 pooches after the operation, they were killed another two years later. After taking out their prostates and calculating their volume and weight, the sections of the prostates were checked by microscope to observe their histology and pathology changes. RESULTS: There were significant differences of weight and volume as well as the changes of histology and pathology between group A and group C (P < 0.01). It was the same with group B and D (hyperplasia changes). CONCLUSIONS: Vasoligation and deferent vein ligation before benign prostatic hyperplasia at pooches grow-up stage can reduce the extent of BPH at old age, and treatment after benign prostatic hyperplasia can make prostatic tissue appear different degrees of atrophy.

Animals↗

Microwave applicators for thermotherapy of benign prostatic hyperplasia: a primer.

Microwave thermotherapy for treatment of benign prostatic hyperplasia (BPH) is becoming increasingly more common. This article provides an introduction to the functional principles of microwave antennas for delivery of energy to the prostatic gland. Different antenna designs (monopole, dipole, and helical coil types) and impedance matching are discussed.

Humans↗

Ammonium-chloride-induced prostatic hypertrophy in vitro: urinary ammonia as a potential risk factor for benign prostatic hyperplasia.

To test the possibility that urinary ammonia could be a risk factor for benign prostatic hyperplasia (BPH), we explored the cellular effects of ammonium chloride (NH(4)Cl) on prostatic cancer cells used as an experimental model. Following treatment of human prostatic cancer DU-145 cells with the varying concentrations of NH(4)Cl for 3 days, cell growth was inhibited by approximately 50% at 5 mM NH(4)Cl and almost completely inhibited at 10 mM NH(4)Cl. However, the individual cell size in these treated cells became approximately 2-fold larger and cellular protein content was also up to 2.5-fold greater than in untreated cells. This protein increase appeared to result from the reduced protein degradation, verified by metabolic labeling with [(14)C]valine. Western blot analysis further suggested that such reduced protein turnover could in part be due to the inactivation of a lysosomal acid protease, cathepsin D. Taken together, these studies demonstrate NH(4)Cl-induced hypertrophy in prostatic cancer cells, as evidenced by the growth inhibition, cell enlargement, and cellular protein increase. Therefore, ammonia is not an inert metabolic product; instead, its chronic effects on the prostate may ultimately lead to significant cellular and biochemical alterations of the prostate such as BPH.

Ammonia↗

Minimally invasive therapies for benign prostatic hyperplasia in the new millennium: long-term data.

Over the last decade, a number of minimally invasive therapies have been investigated for the treatment of symptomatic benign prostatic hyperplasia. Most of these therapies use thermal energy to ablate prostatic tissue. The major common problem with all these new minimally invasive therapies has been the lack of long-term data concerning efficacy, re-intervention rates and side-effects. We present here the available long-term data on these alternative minimally invasive therapies for benign prostatic hyperplasia and their current place in the urologist's armamentarium.

Catheter Ablation↗

Interstitial laser coagulation in benign prostatic hyperplasia: A critical evaluation after 2 years of follow-Up.

Since 1993 we have prospectively followed a cumulative cohort of males with benign prostatic hyperplasia and symptomatic bladder outlet obstruction who underwent interstitial laser coagulation (ILC) of the prostate. We evaluated the safety and efficacy of ILC with respect to relief of symptoms and bladder outlet obstruction. In addition to the critical evaluation of our clinical results, the perineal and transurethral approaches were investigated as they may make a substantial impact on the overall success rate, including prostate size, number of sticks per prostate volume and type of application. A total of 59 patients were treated with the Nd-YAG laser (mediLas fibertom) between April 1993 and December 1996. At the time of reevaluation, 47 patients had completed a follow-up of up to 24 months. A perineal approach was used in 34%, transurethral in 23%, and a combined approach in 43% of the patients, depending on the preoperative volume of the prostate. 75% were high-risk patients in accordance with the ASA score (ASA III). The efficacy of treatment was assessed 6, 12, 24 and 52 weeks postoperatively in accordance with the International Prostate Symptom Score (IPS/quality of life), cystomanometric studies, peak urinary flow rate, residual volume and volume reduction of the prostate. Reduction of prostatic volume and sticks used per prostate volume were correlated to the overall success rate. A significant improvement in all voiding parameters (flow rate, residual volume), including the symptom score, was observed. P(det) decreased from an average of 90 cm H(2)O preoperatively to 42 cm H(2)O postoperatively after 24 weeks and the mean reduction in prostate volume was 14 cm(3). Interestingly, it was noted that the overall success rate was not size-related. A distinct positive correlation was found in the number of sticks performed and the improvement in objective and subjective parameters. In view of the low morbidity outcome, especially in high-risk patients, we proclaim Nd-YAG interstitial laser coagulation of the prostate to be an effective and safe alternative method of treatment for symptomatic benign prostatic hyperplasia.

Aged↗

Prostatitis in benign prostatic hyperplasia: a histological, bacteriological and clinical study.

The paper deals with the incidence of prostatitis in benign prostatic hyperplasia (BPH) and its effect on the postoperative course in the patients subject to the transvesical prostatectomy. The samples of urine and expressed prostatic secretion were bacteriologically analysed before the operation, and samples of urine on three occasions following the operation. Specimens of BPH tissue obtained by surgery were subjected to pathohistological and microbiological examination. The incidence of prostatitis was found to be 90.3%. In the specimens of BPH tissue obtained by transversal prostatectomy, Gram-positive microorganisms were isolated in 32.8% of the tissue. In particular, Staphylococcus epidermidis was found in 26.6% of BPH tissue. Gram-negative microorganisms were isolated in 30.8% of BPH tissue, and fungi in 2.9%. In 27.9% of BPH tissue a microorganism could not be isolated although pathohistological examination evidenced prostatitis. Therefore, in these cases etiology remained unclear. Patients with Gram-negative prostatitis had the highest number of complications and the longest period of postoperative hospitalization. Preoperative and postoperative antibiotic therapy reduced the incidence of postoperative complications and shortened the period of hospitalization in the patients with significant Gram-negative bacteriuria before operation, that is, in the patients with Gram-negative prostatitis in BPH.

Aged↗

[Semi-radical transurethral resection of the prostate for small benign prostatic hyperplasia].

The conventional method of transurethral resection of the prostate (TUR-P) is often not beneficial for small benign prostatic hyperplasia (BPH) because of a high frequency of postoperative bladder neck contracture (BNC). Herein, we examined the usefulness of semi-radical transurethral resection of the prostate (semi-radical TUR-P) from the view points of improvement of peak flow rate, the frequency of postoperative BNC and incidental carcinoma of the prostate in 79 cases of small BPH (group A) and 101 cases (group B) of large BPH in which less than 10 g for more than 10 g of the internal glands was resected, respectively. The bladder neck was resected carefully to avoid over resection which may cause BNC in small BPH cases. Satisfactory results were obtained in both groups, that is, the improvement of the peak flow rate from 7.03 +/- 3.79 ml/sec to 13.9 +/- 7.32ml/sec and from 4.96 +/- 2.88 ml/sec to 15.2 +/- 8.30 ml/sec, and the frequency of BNC were 2.53% (2/79) and 1.98% (2/101) in groups A and B, respectively. The frequency of incidental carcinoma of the prostate were 15.2% (12/79) and 17.8% (18/101) in groups A and B. We conclude that semi-radical TUR-P is a favorable maneuver for small BPH because of satisfactory improvement in peak flow rate with low frequency of postoperative BNC and its superiority in screening test for incidental carcinoma of the prostate.

Aged↗

The emerging role of alpha antagonists in the therapy of benign prostatic hyperplasia.

The rationale for using alpha blockade to treat benign prostatic hyperplasia (BPH) is based on the physiology and pharmacology of prostate smooth muscle. Approximately 20% of the area density of the prostate adenoma is smooth muscle. In vitro isometric tension studies have demonstrated that the contractile properties of the human prostate adenoma are mediated primarily by alpha 1 adrenoceptors. Alpha blockers presumably decrease the resistance along the prostatic urethra by relaxing the smooth muscle component of the prostate. Over the past 14 years, at least 16 clinical trials have confirmed the efficacy of alpha blockade in the treatment of BPH. The primary advantage of terazosin over all other commercially available alpha blockers is that its longer half-life allows for a once-daily dosage regimen. Two Phase II studies conducted in the United States, a multicenter dose titration randomized withdrawal study and the author's personal experience with terazosin, are summarized in this report. Overall, the peak urinary flow rate increased 50% and the mean urinary flow rate increased 46% following terazosin therapy. The mean obstructive and irritative scores improved 67% and 35%, respectively. The adverse reactions occurring with an incidence greater than 5% included headache (10%), asthenia (7%), and dizziness (14%). All adverse events were reversible on termination of therapy. The preliminary experiences with alpha blockers for the treatment of BPH has been very encouraging. Yet, the definitive role of alpha blockade in BPH awaits the reporting of multicenter, randomized placebo-controlled studies.

Adrenergic alpha-Antagonists↗

Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling.

Critical aspects of the biology and molecular basis for prostate malignancy remain poorly understood. To reveal fundamental differences between benign and malignant growth of prostate cells, we performed gene expression profiling of primary human prostate cancer and benign prostatic hyperplasia (BPH) using cDNA microarrays consisting of 6500 human genes. Frozen prostate specimens were processed to facilitate extraction of RNA from regions of tissue enriched in either benign or malignant epithelial cell growth within a given specimen. Gene expression in each of the 16 prostate cancer and nine BPH specimens was compared with a common reference to generate normalized measures for each gene across all of the samples. Using an analysis of complete pairwise comparisons of expression profiles among all of the samples, we observed clearly discernable patterns of overall gene expression that differentiated prostate cancer from BPH. Further analysis of the data identified 210 genes with statistically significant differences in expression between prostate cancer and BPH. These genes include many not recognized previously as differentially expressed in prostate cancer and BPH, including hepsin, which codes for a transmembrane serine protease. This study reveals for the first time that significant and widespread differences in gene expression patterns exist between benign and malignant growth of the prostate gland. Gene expression analysis of prostate tissues should help to disclose the molecular mechanisms underlying prostate malignant growth and identify molecular markers for diagnostic, prognostic, and therapeutic use.

Gene Expression Profiling↗

Comparative study of concentration of isoflavones and lignans in plasma and prostatic tissues of normal control and benign prostatic hyperplasia.

OBJECTIVE: Isoflavones and lignans are phytoestrogens that have recently gained interest as dietary factors related to prostatic diseases. However, no data on the concentrations in prostate tissue in humans is available. Therefore, the concentrations of isoflavones and lignans in plasma and prostatic tissues according to the prostate volume were compared to determine their possible effect on the benign prostatic growth. METHODS: Fasting plasma and prostatic tissue specimens were acquired from 25 men over 50 years of age with similar normal dietary habits and no previous history of drug intake that could affect the isoflavones and lignans levels. The tissue was acquired either during a transurethral resection of the prostate in 15 patients with benign prostatic hyperplasia (BPH) with prostate volume over 40 ml or during a radical cystoprostatectomy in 10 patients with bladder cancer with a prostate volume < 25 ml, who were used as the controls. Quantitative analysis of the isoflavones, specifically equol, daidzein and genistein and lignans, particularly enterodiol and enterolactone, was performed by gas chromatography-mass spectrometry. RESULTS: The mean prostatic concentrations of enterodiol, enterolactone, equol and daidzein in the BPH and the control groups were similar. However, the mean prostatic concentration of genistein was significantly lower in the BPH group than in the control group (65.43 +/- 17.05 vs 86.96 +/- 37.75 ng/ ml, respectively, p=0.032). The plasma concentration of isoflavones and lignans in the two groups were comparable. CONCLUSION: Isoflavones, but not lignans, have some influence the benign prostatic growth, and the prostatic concentration of genistein possibly has the closest association among them. More studies to further clarify the roles and mechanisms of isoflavone action on BPH including pharmacokinetic studies are recommended.

Blood↗

Comparison of fatty acid profiles in the serum of patients with prostate cancer and benign prostatic hyperplasia.

OBJECTIVE: The role of dietary fatty acids (FAs) in benign and malignant prostatic diseases was investigated by comparing the composition value of serum fatty acids in the normal controls, and patients with prostate cancer (PC) and benign prostatic hyperplasia (BPH). Also, to estimate a possible association between PC risk and PUFAs, omega-3, omega-6 and omega-3/omega-6 FA composition ratios were compared among these groups. METHODS: Serum samples were obtained from 24 BPH and 19 PC patients, and from 21 age-matched normal male subjects. The serum concentration of 21 fatty acids was determined using gas chromatography/mass spectrometry. RESULT: The proportional values of saturated fatty acids (SFAs) groups demonstrated no specific difference between the control subjects and the patients. In the polyunsaturated fatty acids (PUFAs), we found that the omega-3 PUFAs level was significantly decreased in patient with BPH and PC and that the omega-6 PUFAs level was increased in PC only. The ratio of omega-3/omega-6 PUFAs decreased in the following order of normal, BPH, and PC. CONCLUSION: It was proposed that the changed composition level of PUFAs including omega-3 and omega-6 PUFAs have certain relationship with both prostatic diseases. Therefore, the ratio of omega-3/omega-6 PUFAs also may have an important association with the benign and malignant status of prostatic disease.

Case-Control Studies↗

Protective effect of Prostane in experimental prostatic hyperplasia in rats.

AIM: Prostane, a polyherbal formulation, was evaluated for its efficacy on 5alpha-reductase inhibition, alpha-adrenergic antagonistic activity and testosterone-induced prostatic hyperplasia. METHODS: 5alpha-reductase inhibition was evaluated using rat prostate homogenate as an enzyme source. Adrenergic antagonistic activity was evaluated using isolated rat vas deferens. Experimental prostatic hyperplasia was induced in rats by giving testosterone 3 mg/kg sc for 21 days. RESULTS: Prostane dose-dependently inhibited 5alpha-reductase activity and exhibited alpha-adrenergic antagonistic activity. Treatment with Prostane at 250, 500 and 750 mg/kg body wt, po for 21 days significantly reduced the prostatic weight, the epithelial height and the stromal proliferation in experimental prostatic hypertrophy. CONCLUSION: Prostane is effective in the treatment of experimental prostatic hypertrophy in rats and may be passed on to clinical trials on benign prostatic hypertrophy after necessary toxicological evaluations.

Animals↗

Are clinical characteristics of familial benign prostatic hyperplasia different than in sporadic cases?

OBJECTIVE: Familial benign prostatic hyperplasia (BPH) is a recently popularized entity with yet uncertain clinical and pathological features. In the present study we investigated whether there was any difference between clinical characteristics of familial and sporadic BPH in a series of 148 surgically treated BPH patients. MATERIALS AND METHODS: A retrospective analysis was performed in 148 patients subjected to transvesical or transurethral prostatectomy to determine the clinical features of familial BPH. Patients were categorised as having familial BPH when 3 or more (including the patient) first-degree family members gave a history of BPH. Accordingly 23 cases who fit this criterion were accepted as having familial BPH and the rest of the cases were taken as the control group. The two groups were compared with respect to age, International Prostate Symptom Score (IPSS), quality of life score, prostate specific antigen (PSA), maximum urinary flow rate and the weight of the surgical prostate specimen. RESULTS: The mean age, IPSS, quality of life score, total PSA, maximum urinary flow rate and the weight of the surgical prostate specimen were found as 65.13 +/- 5.51 years, 23.13 +/- 4.82, 4.78 +/- 0.95, 6.0 +/- 4.1 ng/ml, 6.9 +/- 2.7 ml/s and 62.96 +/- 38.76 g, respectively, in the familial BPH group whereas the same parameters were measured as 68.13 +/- 7.68 years, 24.74 +/- 3.73, 4.52 +/- 0.85, 5.93 +/- 4.75 ng/ml, 4.6 +/- 1.71 ml/s and 70.87 +/- 53.21 g, respectively. No significant difference was present between familial and sporadic BPH cases in any of the studied parameters. CONCLUSION: The clinical features of familial BPH did not differ significantly from those of sporadic BPH.

Aged↗

Studies on the proliferation, secretory activities, and epidermal growth factor receptor expression in benign prostatic hyperplasia explant cultures.

Short term explant cultures of benign prostatic hyperplasia (BPH) tissues were studied immunohistochemically to characterise both the morphological changes within the explant tissue and the cellular origin of the epithelial cell outgrowth. Altered patterns of expression of cytokeratins, prostate specific antigen (PSA) prostatic acid phosphatase (PAP), and epidermal growth factor (EGF) receptor were observed. After sloughing of the secretory epithelium in the majority of the acini repopulation and outgrowth of a monolayer was accomplished by cells which were strongly positive for stratifying keratin and EGF receptor and negative for PAP and PSA, indicative of a basal cell phenotype. The peak of proliferation in the acini, as assessed by Ki-67 immunohistochemistry, occurred after 2-4 days in culture. Preliminary studies on BPH tissue xenografts in nude mice indicated that better preservation of normal morphology, secretory activity, and antigen expression could be achieved.

Acid Phosphatase↗