Human Benign Prostatic Hyperplasia Research Articles

Androgen-stimulated human prostate epithelial growth mediated by stromal-derived fibroblast growth factor-10.

It has been suggested that prostate homeostasis is regulated indirectly by androgens through stromal-epithelial interactions in part by factors from the stromal cells acting on receptors in epithelial cells. In this report, the role of fibroblast growth factor (FGF)-10 in prostatic epithelial proliferation was investigated. The expression of FGF-10 mRNA was apparent in primary-cultured stromal cells, but not in epithelial cells derived from human tissue from patients with benign prostatic hyperplasia (BPH). The mitogenic activity of human recombinant FGF-10 assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation was demonstrated in isolated epithelial cells, but not in cultured stromal cells. No mitogenic activity of dihydrotestosterone (DHT) for either epithelial or stromal cells could be demonstrated, but quantitative PCR (real-time PCR) with a double-labeled fluorogenic probe demonstrated that expression of FGF-10 in stromal cells was enhanced 5.3-fold at a DHT concentration of 100 pM. Androgen receptor mRNA levels showed no significant change with DHT at concentrations less than 100 pM, but were reduced to 50% of control levels at a DHT concentration of 10 nM. These results suggest that stromal-derived FGF-10 stimulates human prostatic epithelial growth and its mRNA expression is induced by androgens, without an increase in the androgen receptor mRNA. Moreover, FGF-10 may be involved in the development or support of human BPH.

CAN THE INTRAPROSTATIC CONCENTRATION OF EPIDERMAL GROWTH FACTOR INFLUENCE THE VARIANCE OF SERUM PROSTATE SPECIFIC ANTIGEN LEVELS IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA?

Except for prostate volume, little is known about the factors influencing serum prostate specific antigen (PSA) levels. Considering that dihydrotestosterone and epidermal growth factor are regulators of the proliferation and differentiation in the epithelial component of human prostate tissue and that PSA is produced only by the epithelial cells of the gland, studies were performed on patients with a histological diagnosis of benign prostatic hyperplasia (BPH) to establish whether a significant association exists between the intraprostatic concentration of dihydrotestosterone or epidermal growth factor and serum PSA levels.A total of 20 patients with BPH who had not been previously treated were part of a larger study on the correlation among PSA, prostate volume and age, and were evaluated according to the algorithm in the guidelines of the international consultation on BPH. All men underwent open suprapubic prostatectomy to enucleate the entire adenoma and in each case sections were made in the periurethral, subcapsular and intermediate zones of the BPH tissue. Dihydrotestosterone and epidermal growth factor concentrations were evaluated by radioimmunoassay in the periurethral zone and in total BPH tissue.In these 20 patients with BPH serum PSA levels were significantly associated with epidermal growth factor but not with dihydrotestosterone concentrations in total BPH tissue (r = 0.7762, p = 0.00002836 and r = 0.3923, p = 0.0956307, respectively). A stronger association was found between PSA levels and the periurethral concentration of epidermal growth factor and dihydrotestosterone (r = 0.8117, p = 0.000005 and r = 0.5656, p = 0.0098326, respectively). On the contrary, epidermal growth factor and dihydrotestosterone were not significantly associated with prostate volume (p = 0.957415 and p = 0.531439, respectively).To our knowledge this study is the first report in the literature to demonstrate an association between serum PSA, and dihydrotestosterone and epidermal growth factor levels, particularly in the periurethral zone of human BPH tissue. These data suggest the importance of epidermal growth factor and dihydrotestosterone in influencing serum PSA levels.

Can the intraprostatic concentration of epidermal growth factor influence the variance of serum prostate specific antigen levels in patients with benign prostatic hyperplasia?

Except for prostate volume, little is known about the factors influencing serum prostate specific antigen (PSA) levels. Considering that dihydrotestosterone and epidermal growth factor are regulators of the proliferation and differentiation in the epithelial component of human prostate tissue and that PSA is produced only by the epithelial cells of the gland, studies were performed on patients with a histological diagnosis of benign prostatic hyperplasia (BPH) to establish whether a significant association exists between the intraprostatic concentration of dihydrotestosterone or epidermal growth factor and serum PSA levels. A total of 20 patients with BPH who had not been previously treated were part of a larger study on the correlation among PSA, prostate volume and age, and were evaluated according to the algorithm in the guidelines of the international consultation on BPH. All men underwent open suprapubic prostatectomy to enucleate the entire adenoma and in each case sections were made in the periurethral, subcapsular and intermediate zones of the BPH tissue. Dihydrotestosterone and epidermal growth factor concentrations were evaluated by radioimmunoassay in the periurethral zone and in total BPH tissue. In these 20 patients with BPH serum PSA levels were significantly associated with epidermal growth factor but not with dihydrotestosterone concentrations in total BPH tissue (r = 0.7762, p = 0.00002836 and r = 0.3923, p = 0.0956307, respectively). A stronger association was found between PSA levels and the periurethral concentration of epidermal growth factor and dihydrotestosterone (r = 0.8117, p = 0.000005 and r = 0.5656, p = 0.0098326, respectively). On the contrary, epidermal growth factor and dihydrotestosterone were not significantly associated with prostate volume (p = 0.957415 and p = 0.531439, respectively). To our knowledge this study is the first report in the literature to demonstrate an association between serum PSA, and dihydrotestosterone and epidermal growth factor levels, particularly in the periurethral zone of human BPH tissue. These data suggest the importance of epidermal growth factor and dihydrotestosterone in influencing serum PSA levels.

THE PATHOGENESIS OF BENIGN PROSTATIC HYPERPLASIA: A PROPOSED HYPOTHESIS AND CRITICAL EVALUATION

Purpose We used expanding observations regarding effects of testicular epididymal plasma and nonandrogenic testis factor(s) (NATF) on prostate growth to propose and evaluate a hypothesis regarding the development of benign prostatic hyperplasia (BPH) in man. Materials and Methods Current experimental data regarding the presence of NATF were reviewed. The potential for their exposure to the prostate by various routes was assessed. These observations were coupled with recognized anatomical, histological and epidemiological characteristics of BPH to construct a hypothesis regarding its pathogenesis. Results In vivo observations in man, rats and dogs supported the systemic secretion of NATF. These factors probably are, at least in part, spermatogenesis related. In vitro evaluation of the effect of spermatocele derived testicular epididymal plasma on human prostate stromal cells indicated the presence of androgen independent and androgen synergistic stromal growth promoters. These factors have potential local and systemic access to the prostate. The almost ubiquitous development of a regional, histologically variegated nodular growth occurring in the prostate in the androgen diminished environment of the aging man is compatible with local as well as systemic exposure to an age associated secretion of NATF. Conclusions We propose that human BPH is an induced phenomenon that is usually initiated by local episodic exposure of periurethral prostate to mitogens secreted by the testis/epididymis. Once initiated, isolated or complex interacting proliferative stimuli from the testis/epididymis and a variety of other sources may achieve exposure to the prostate by several routes and stimulate prostate growth.

The pathogenesis of benign prostatic hyperplasia: a proposed hypothesis and critical evaluation.

We used expanding observations regarding effects of testicular epididymal plasma and nonandrogenic testis factor(s) (NATF) on prostate growth to propose and evaluate a hypothesis regarding the development of benign prostatic hyperplasia (BPH) in man. Current experimental data regarding the presence of NATF were reviewed. The potential for their exposure to the prostate by various routes was assessed. These observations were coupled with recognized anatomical, histological and epidemiological characteristics of BPH to construct a hypothesis regarding its pathogenesis. In vivo observations in man, rats and dogs supported the systemic secretion of NATF. These factors probably are, at least in part, spermatogenesis related. In vitro evaluation of the effect of spermatocele derived testicular epididymal plasma on human prostate stromal cells indicated the presence of androgen independent and androgen synergistic stromal growth promoters. These factors have potential local and systemic access to the prostate. The almost ubiquitous development of a regional, histologically variegated nodular growth occurring in the prostate in the androgen diminished environment of the aging man is compatible with local as well as systemic exposure to an age associated secretion of NATF. We propose that human BPH is an induced phenomenon that is usually initiated by local episodic exposure of periurethral prostate to mitogens secreted by the testis/epididymis. Once initiated, isolated or complex interacting proliferative stimuli from the testis/epididymis and a variety of other sources may achieve exposure to the prostate by several routes and simulate prostate growth.

In vitro inhibition of androstenedione 5 α-reduction by finasteride in epithelium and stroma of human benign prostatic hyperplasia

Finasteride is a well known steroid 5 α-reductase inhibitor. In this context, recently we have shown that in human benign prostatic hyperplasia (BPH) finasteride inhibits the 5 α-reduction of testosterone to dihydrostestosterone (DHT) more effectively in the epithelium as compared to the stroma. The aim of the present study was to describe in epithelium and stroma of human BPH the effect of finasteride on the 5 α-reduction of androstenedione, that is the second main circulating androgen in men, to androstanedione. Using a finasteride concentration of 75 nM and an androstenedione concentration of 220 nM, the mean inhibition [%±SEM] of 5 α-reductase activity was significantly higher in epithelium (69±2) than in stroma (52±4). Both in epithelium and stroma, this inhibition of 5 α-reductase activity was dose-dependent and competitive. Dixon plots as well as slope replots of Lineweaver–Burk plots showed that the mean inhibition constant K i (nM±SEM) was significantly lower in epithelium (10±1 and 11±2, respectively) than in stroma (33±7 and 28±4, respectively) indicating a significantly stronger inhibitory effect of finasteride in epithelium. From those mean K i values, it follows that in human BPH finasteride inhibits equally well both the 5 α-reduction of androstenedione to androstanedione and testosterone to DHT. Based on these inhibition studies, there is no evidence for the coexistence of substrate-specific 5 α-reductases converting either testosterone or androstenedione. However, the striking difference in finasteride sensitivity of the 5 α-reduction between epithelium and stroma could be due to a cell-type specific expression of structurally different 5 α-reductases as well as to a different access of finasteride to 5 α-reductase in epithelium and stroma where, compared to each other, the lipid environment is significantly different.

Fatty acid composition of phospholipids in epithelium and stroma of human benign prostatic hyperplasia.

Although it is well known that prostatic 5alpha-reductase is active only in its membrane-bound form, rather limited information is available concerning the composition of cellular lipids in human BPH. Therefore, in the present study, the phospholipid fatty acid composition and content in epithelium and stroma of human BPH have been investigated for the first time. Phospholipids separated on TLC plates were methylated and fatty acid methyl esters were analyzed by capillary gas chromatography. The fatty acid composition of total phospholipids was significantly different between epithelium and stroma. In particular, the percentage of oleic acid was significantly higher in epithelium as compared with stroma, whereas that of arachidonic acid was significantly lower in epithelium than in stroma. In addition, significant differences between epithelium and stroma were found in regard to the fatty acid composition of the main phospholipid subclasses. Another remarkable finding were the age-dependent changes of the fatty acid composition in human BPH. This study shows that the fatty acid composition of phospholipids is significantly different between epithelium and stroma of human BPH. Furthermore, age-dependent alterations of the fatty acid composition were found. Further studies are needed to determine whether the endogenous hormonal milieu in the prostate modulates the fatty acid composition of the prostatic cells, as well as what impact such modulation could have on the properties of membrane proteins, i.e., enzymes like the 5alpha-reductase and receptors, which are thought to be affected by alterations in membrane fluidity or composition, or both.

Fatty acid composition of phospholipids in epithelium and stroma of human benign prostatic hyperplasia

BACKGROUND Although it is well known that prostatic 5α-reductase is active only in its membrane-bound form, rather limited information is available concerning the composition of cellular lipids in human BPH. Therefore, in the present study, the phospholipid fatty acid composition and content in epithelium and stroma of human BPH have been investigated for the first time. METHODS Phospholipids separated on TLC plates were methylated and fatty acid methyl esters were analyzed by capillary gas chromatography. RESULTS The fatty acid composition of total phospholipids was significantly different between epithelium and stroma. In particular, the percentage of oleic acid was significantly higher in epithelium as compared with stroma, whereas that of arachidonic acid was significantly lower in epithelium than in stroma. In addition, significant differences between epithelium and stroma were found in regard to the fatty acid composition of the main phospholipid subclasses. Another remarkable finding were the age-dependent changes of the fatty acid composition in human BPH. CONCLUSIONS This study shows that the fatty acid composition of phospholipids is significantly different between epithelium and stroma of human BPH. Furthermore, age-dependent alterations of the fatty acid composition were found. Further studies are needed to determine whether the endogenous hormonal milieu in the prostate modulates the fatty acid composition of the prostatic cells, as well as what impact such modulation could have on the properties of membrane proteins, i.e., enzymes like the 5α-reductase and receptors, which are thought to be affected by alterations in membrane fluidity or composition, or both. Prostate 36:235–243, 1998. © 1998 Wiley-Liss, Inc.

Coexpression of gonadotropic hormones and their corresponding FSH- and LH/CG-receptors in the human prostate.

Benign prostatic hyperplasia (BPH) affects the majority of elderly men, and prostate cancer is the most common male cancer. Prostatic growth and function are thought to be regulated by steroid hormones, primarily androgens and estrogens, but nonandrogenic hormones must also be considered. The increasing evidence of para/autocrine functions of the gonadotropic glycoprotein-hormones (GPH), their allocation to the superfamily of cystine-knot growth factors, and luteinizing hormone (LH)/chorionic gonadotropin (CG)-receptor (R) gene expression in nongonadal tissues led us to investigate intraprostatic GPH and GPH-R gene expression. RT-PCR and subsequent Southern hybridization and/or restriction enzyme analysis of BPH and prostatic adenocarcinoma demonstrated that all three human (h) gonadotropic hormones, i.e., follicle-stimulating hormone (FSH), LH, and CG, as well as the corresponding FSH-R and LH/CG-R, are transcribed intraprostatically. Significant amounts of the alpha and beta subunits of hCG were secreted by short-term primary cultures of human BPH tissues, as detected by highly sensitive and specific time-resolved immunofluorometric assays (IFMAs). Our data suggest that prostatic- and pituitary-derived GPH act directly on the prostatic gland, particularly FSH via the FSH-R, thereby possibly modulating locally acting key hormones and growth factors involved in BPH development.

Insulin-Like Growth Factor-I and -II in Human Benign Prostatic Hyperplasia: Relationship with Binding Proteins 2 and 3 and Androgens

In prostatic tissue, androgen action may be mediated by growth factors such as insulin-like growth factor-I (IGF-I) and II (IGF-II), which are mitogenic for prostatic cells and modulate the stroma–epithelium interaction. IGF-binding proteins (IGFBPs) have an autocrine and/or paracrine role in regulating the local actions of the IGFs. In this study, testosterone, dihydrotestosterone (DHT), 3αandrostanediol (3αdiol), IGF-I, IGF-II, IGFBP2, and IGFBP3 concentrations were evaluated in human benign prostatic hyperplasia (BPH) tissue. Samples of prostate tissue were removed by suprapubic prostatectomy from twelve BPH patients. Androgen tissue levels were determined by radioimmunoassay after purification on celite microcolumns. IGF-I, IGFBP2, and IGFBP3 were measured by radioimmunoassay, and IGF-II by immunoradio metric assay, after acidification and chromatography on Sep-pak C18 Cartridges for IGF-I and IGF-II. Androgen concentrations, expressed in ng/g tissue (mean ± SE), were 0.51 ± 0.05 for testosterone, 5.3 ± 0.16 for DHT, and 1.1 ± 0.07 for 3αdiol. IGF-I, IGF-II, IGFBP2, and IGFBP3 levels were 24 ± 3.7, 121 ± 14 ng/g tissue and 0.44 ± 0.05 and 1.2 ± 0.17 μg/g tissue, respectively. No correlation between IGF-I, androgens, and IGFBPs was found. IGF-II was positively correlated with DHT ( r = 0.78; p = 0.003) and 3αdiol ( r = 0.66; p = 0.021) but not with IGFBPs. These data suggest that in BPH, DHT modulates the IGF system by increasing IGF-II without modifying IGFBPs. Therefore, the stroma–epithelium interaction, which plays an important role in prostatic growth, may be regulated by DHT through IGF-II.

Role of cavitation during high intensity focused ultrasound treatment of prostate tissue

The use of high intensity focused ultrasound (HIFU) has been well established to produce deep seated tissue necrosis using a short time ultrasound exposure. The scavenging system of the body replaces the necrosed tissue over time from the treated organ. However, in the case of benign prostatic hyperplasia (BPH) treatment, it is essential to remove treated tissue immediately after the treatment to offer improved urine flow rate and relief from the symptoms. Therefore, it was necessary to develop an ultrasound treatment system that not only provides thermal lesions that are deep in the tissue but also mechanical disintegration of urethra and surrounding tissue. Once the urethra is mechanically disintegrated, the necrosed tissue is sloughed with urine and provides an improved flow rate. The mechanical defect in tissue is produced using the cavitation process. The acoustic cavitation is produced by inserting a silastic catheter in the urethra. The catheter blocks the HIFU energy and produces standing waves which produce cavitation, and converts HIFU in a thermal dose larger than that produced by only absorption of acoustic energy by tissue. This method of treatment yields far greater results. The system is now being used in human BPH treatment.

The localisation and expression of 5 alpha-reductase types I and II mRNAs in human hyperplastic prostate and in prostate primary cultures.

The expression and localisation of mRNAs for 5 alpha reductase Type I (5 alpha R-I) and Type II (5 alpha R-II) isoenzymes in human benign prostatic hyperplasia (BPH) were investigated by RT-PCR and by in mini hybridisation (ISH) using digoxigenin labelled riboprobes. In addition, we also examined the isoenzymes mRNA expression in primary BPH cultures of separated stroma/fibroblast and epithelial cells to determine whether primary cultures are appropriate models in which to investigate 5 alpha R activity and regulation. The results demonstrated conclusively the presence of mRNA encoding both isoenzymes in all specimens so far examined. Additionally, the presence of a functional 5 alpha R-I and -II activity in BPH was confirmed by enzyme assays. ISH studies localised the mRNA expression to both the fibroblast/stromal component as well as the epithelial cells of the hyperplastic tissue. In the glandular regions the expression for both isoenzymes was particularly strong in the basal layers of the epithelium whereas mRNA expression in the secretory cells was less pronounced. Expression of 5 alpha R-I and -II mRNAs in fibroblast was on the other hand variable with high expression in some areas and little in others. These findings were supported by our primary culture experiments which demonstrated that both the fibroblast and epithelial cells maintain a capacity to express both isoenzymes in vitro. In the case of the fibroblast, the capacity to express the isoenzymes was maintained following the sequential passaging of the cells up to passage 6, after which the cells no longer expressed either isoenzyme.

Evaluation of histological structure and its effect on the distribution of alpha1-adrenoceptors in human benign prostatic hyperplasia.

To evaluate the histological structure of benign prostatic hyperplasia (BPH) and its relationship with the density of alpha1-adrenoceptors in smooth muscle. Specimens from hyperplastic tissues obtained from 14 patients with BPH were evaluated for the density of alpha1-adrenoceptors in smooth muscle using autoradiography, Mallory-Azan staining and computer-assisted image analyses. The binding of [3H] tamsulosin (a selective alpha1-blocker) and the ratio of smooth muscle area was calculated, and the density of alpha1-adrenoceptors per area of smooth muscle determined by dividing the degree of binding by the ratio of smooth muscle to total area. There was a significant difference between the ratio of smooth muscle area in the hyperplastic acinar nodule and the surrounding stroma (P < 0.01). The density of alpha1-adrenoceptor per smooth muscle area was significantly higher in the hyperplastic acinar nodule than in the surrounding stroma (P < 0.05). There was no correlation between prostatic weight and the ratio of smooth muscle area or the density of alpha1-adrenoceptors in each region. The distribution of alpha1-adrenoceptors on smooth muscle differed with histological structure; both the histological conformation and the difference in the distribution of alpha1-adrenoceptors could affect urethral obstruction in BPH.

A novel coculture model for benign prostatic hyperplasia expressing both isoforms of 5 alpha-reductase.

We have developed a coculture system for primary fibroblast and epithelial cells derived from benign prostatic hyperplasia (BPH) that retained many of the characteristics of the intact human prostate. In contrast to separately cultured prostate fibroblast and epithelial cells, cocultures of fibroblasts and epithelial cells maintained messenger ribonucleic acid expression and functional activity for both isoenzymes of 5 alpha-reductase (type I and type II) as well as maintained expression of androgen receptors and prostate-specific antigen. Furthermore, levels of prostate-specific antigen secreted by cocultured epithelial cells were increased by treatment with androgens, mimicking the situation in the human gland. This contrasted with conventionally cultured fibroblasts or epithelial cells, which failed to express 50 alpha-reductase type II and rapidly lost expression of androgen receptors and androgen sensitivity upon being placed into culture. Electron microscopy demonstrated intracellular structures indicative of the differentiated state of the cocultured cell types, including round nuclei, tonofibrils, and microvilli in epithelial cells and elongated nuclei; large amounts of Golgi and cilia; along with immature collagen fibers in fibroblasts. The present study demonstrates that the coculture model reflects more closely the in vivo system for human BPH and is thus a far more suitable model for investigating the molecular and cellular events that underlie BPH than current in vitro systems.

E4, a new monoclonal antibody identifying a human prostatic cell surface antigen

The monoclonal antibody E4 (IgG2a, kappa) was raised by immunizing mice with dispersed cells obtained from human benign prostatic hyperplasia (BPH). The antibody identifies an antigen abundantly expressed in normal prostate epithelial cells, in benign epithelial prostatic cells and in well- and moderately well differentiated adenocarcinomas of the prostate, whereas poorly differentiated prostatic adenocarcinomas display somewhat less expression. Investigation of the human prostatic adenocarcinoma cell line DU 145 revealed E4 immunoreactivity localized to the cell surface. SDS-PAGE analysis under reducing conditions demonstrated an approximate molecular weight of 70,000 for the antigen. The highly specific reactivity with prostate tissue, as well as intense surface staining, especially in well- and moderately well differentiated prostatic adenocarcinomas, makes the E4 antibody a useful immunohistochemical marker and a possible candidate for future immunoscintigraphy and/or targeted radiotherapy.

Differential expression of acidic and basic fibroblast growth factors in benign prostatic hyperplasia identified by immunohistochemistry.

To detect the expression and to determine the relative cellular locations of the two peptide growth factors, acidic fibroblast growth factor (a-FGF) and basic (b)-FGF in tissues from human benign prostatic hyperplasia (BPH). A series of 50 sequential and unselected cases of human BPH tissues, obtained after transurethral prostatectomy, was examined. Adjacent sections of formalin-fixed and paraffin wax-embedded tissues were stained immunohistochemically for expression of a-FGF and b-FGF using well-characterized and commercially available antibodies. The stained tissue sections were assessed for the cellular distribution of immunohistochemical products and analysed according to the relative intensity of staining as well as the spatial relationships of positively stained cells. Acidic-FGF was weakly expressed with a pancytoplasmic distribution within luminal glandular epithelial cells in regions of prostatic intra-epithelial neoplasia (both PIN I and II) but not by non-dysplastic normal or hyperplastic tissues. No expression of a-FGF was detected in basal epithelial cells or in the stromal compartment of any tissue examined. In contrast, b-FGF was strongly expressed within the cytoplasm of all basal epithelial cells, but not by luminal epithelial cells, in morphologically normal regions of all cases examined. Basal expression of b-FGF was diminished, or absent, in regions of mild epithelial dysplasia, particularly those strongly expressing a-FGF. Extensive nuclear and cytoplasmic expression of b-FGF occurred predominantly in smooth muscle-type stromal cells but not in all types of stromal cells. This study confirmed both a differential and a reciprocal expression of a- and b-FGF in non-dysplastic prostatic hyperplasia and in mildly dysplastic regions of prostatic tissues. While only small amounts of a-FGF were expressed in BPH, exclusively in the luminal epithelial compartment, its consistent appearance in PIN I and II suggests that it might contribute to the early stages of PIN. Conversely, b-FGF may be an important mediator of stromal-epithelial interaction during the pathogenesis of BPH. These results provide new information about the relative expression of these growth factors, particularly in the architectural relationships between different cell-types within normal and non-malignant prostatic tissues.

Insulin-like growth factor-I and -II in human benign prostatic hyperplasia: Relationships with their binding protein-2 and -3 and and rogens : S. Monti, S. Lanzara, P. A. Varasano, C. Martini, V. Toscano, F. Di Silverio, and F. Sciarra. Department of Medical Physiopathology, III Endocrinology, and Urology, University of Rome La Sapienza, Rome, Italy

Insulin-like growth factor-I and -II in human benign prostatic hyperplasia: Relationships with their binding protein-2 and -3 and and rogens : S. Monti, S. Lanzara, P. A. Varasano, C. Martini, V. Toscano, F. Di Silverio, and F. Sciarra. Department of Medical Physiopathology, III Endocrinology, and Urology, University of Rome La Sapienza, Rome, Italy

Effect of finasteride on the concentrations of testosterone, dihydrotestosterone and 3α-androstanediol in human benign prostatic hyperplasia tissue : S. Monti, P. A. Varasano, S. Lanzara, C. Tosti-Croce, G. D'Eramo, F. Di Silverio, and F. Sciarra. Departments of Medical Physiopathology, III Endocrinology, and Urology, University of Rome La Sapienza, Rome, Italy

Effect of finasteride on the concentrations of testosterone, dihydrotestosterone and 3α-androstanediol in human benign prostatic hyperplasia tissue : S. Monti, P. A. Varasano, S. Lanzara, C. Tosti-Croce, G. D'Eramo, F. Di Silverio, and F. Sciarra. Departments of Medical Physiopathology, III Endocrinology, and Urology, University of Rome La Sapienza, Rome, Italy

Transforming growth factor‐β3 is expressed in nondividing basal epithelial cells in normal human prostate and benign prostatic hyperplasia, and is no longer detectable in prostate carcinoma

Transforming growth factor‐β3 is expressed in nondividing basal epithelial cells in normal human prostate and benign prostatic hyperplasia, and is no longer detectable in prostate carcinoma

High-power (60-watt) potassium-titanyl-phosphate laser vaporization prostatectomy in living canines and in human and canine cadavers

Objectives We studied the safety and efficacy of 60-W potassium-titanyl-phosphate (KTP) laser prostatectomy in living dogs and compared the efficacy with that in fresh human and dog cadavers. Methods Ten dogs underwent 60-W KTP laser prostatectomy and were sacrificed 3 hours (n = 5) or 7 weeks (n = 5) after operation. Two thawed fresh-frozen human cadaver prostates and two thawed fresh-frozen canine prostates were also vaporized with the 60-W KTP laser. All prostates were weighed, measured, serially sectioned, and whole mounted for histologic analysis. Results In dogs, the in vivo procedure was hemostatic, and no irrigant absorption was detected. Prostatic defects with a mean diameter of 3.0 and 2.5 cm at 3 hours and 7 weeks postoperatively, respectively, were produced. With experience, resection time was reduced to 14 minutes. Of the 5 dogs that were studied for 7 weeks, 4 voided immediately after removal of the urethral catheter on the morning after operation, and 1 dog required recatheterization but voided with a strong stream when the urethral catheter was removed 4 days later. All 5 dogs were continent and had normal erectile function postoperatively. Defects of 2.0 and 2.5 cm were produced in the two human cadaver prostates (weight, 29.5 and 55 g) with resection times of 26 and 54 minutes, respectively. Human and canine cadaver prostates required similar energies for tissue vaporization (15.2 and 13.7 kJ/cm 3 cavity created, respectively, P > 0.6), whereas living canine prostates required only 7.0 kJ/cm 5 cavity created ( P < 0.01 compared with cadaver tissue). Conclusions The 60-W KTP laser allows technically easy, safe, rapid, and hemostatic removal of canine prostatic tissue in vivo. Furthermore, there is no difference in the efficacy of KTP laser vaporization between human and canine cadaver prostates. These findings suggest that KTP laser vaporization may be as effective in living human prostates as it is in living dogs, and thus it may be a useful technique in the surgical treatment of human benign prostatic hyperplasia.