Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... following organizations provide information on benign prostatic hyperplasia ( prostate enlargement ): National Kidney and Urologic Diseases Information Clearinghouse - ...
Benign prostate hyperplasia (BPH) occurs in up to 50% of men by age 50, and the incidence increases with age. This common clinical problem is diagnosed by history, including the International Prostate Symptom Score (IPSS) questionnaire, and physical examination by digital rectal examination (DRE). Initial management for BPH includes lifestyle modification, and smooth muscle relaxant alpha blocker therapy. Alpha blockers usually take effect quickly within 3-5 days, and have minimal side effects. Current commonly used alpha blockers include the selective alpha blockers tamsulosin (Flomax), alfusosin (Xatral), and silodosin (Rapaflo). For patients with larger prostates, the 5-alpha reductase inhibitor class (finasteride (Proscar) and dutasteride (Avodart)) work effectively to shrink prostate stroma resulting in improved voiding. The 5-ARI class of drugs, in addition to reducing prostate size, also reduce the need for future BPH-related surgery, and reduce the risk of future urinary retention. Drugs from the phosphodiesterase-5 (PDE-5) inhibitor class may now be considered for treating BPH. Once daily 5 mg tadalafil has been shown to improve BPH-related symptoms and is currently approved to treat patients with BPH. Referral to a urologist can be considered for patients with a rising prostate-specific antigen (PSA), especially while on 5-ARI, failure of urinary symptom control despite maximal medical therapy, suspicion of prostate cancer, hematuria, recurrent urinary infections, urinary retention, or renal failure. Currently the primary care physician is armed with multiple treatment options to effectively treat men with symptomatic BPH. PMID:23089343
Objective: To establish guidelines for the diagnosis, treatment, and follow–up of BPH.Methods: A search of published work was conducted using Medline. In combination with expert opinions recommendations were made on the usefulness of tests for assessment and follow–up: mandatory, recommended, or optional. In addition, indications and outcomes for the different therapeutic options were reviewed.Results: A digital rectal examination is mandatory
Jean J. M. C. H. de la Rosette; Gerasimos Alivizatos; Stephan Madersbacher; Massimo Perachino; David Thomas; François Desgrandchamps; Michel de Wildt
Benign prostatic hyperplasia (BPH) is a common disease in males older than 50 years of age. 75-80% of this population is considered to have some degree of BPH causing clinical symptoms and requiring urological treatment. Transurethral resection of the prostate (TUR-P) is currently the standard surgical treatment modality for BPH. In an attempt to minimize the need for hospitalization and the associated perioperative and postoperative morbidity, alternatives have been sought. Various types of laser techniques such as interstitial laser coagulation and side-firing technology have been proposed. Numerous studies have shown that laser procedures safely and effectively reduce the volume of the prostate. Intra- and postoperative bleeding are nearly unknown complications for laser procedures, whereas this is the most relevant complication for the TUR-P. Due to significant tissue edema after laser treatment, patients commonly show delayed time to void adequately and, therefore, catheter drainage is often necessary for 3 to 21 days. Retrograde ejaculation is reported to occur less (0- 10%) compared to TUR-P (greater than 60%). Urinary tract infections are very common after interstitial laser coagulation. Although not many long-term clinical data are available, various studies have shown that BPH patients improve in symptom score, flow rate and post-void residual up to 3 years after laser treatment. This paper presents a concise review of efficacy, advantages and disadvantages of the most frequently used laser techniques as well as the long-term clinical data compared to TUR-P.
de Riese, Werner T.; Sharpe, Brent A.; Aronoff, David B.; Mittemeyer, Bernhard T.
Early studies suggested macrophages might play roles in inflammation-associated benign prostatic hyperplasia (BPH) development, yet the underlying mechanisms remain unclear. Here we first showed that CD68(+) macrophages were identified in both epithelium and the stromal area of human BPH tissues. We then established an in vitro co-culture model with prostate epithelial and macrophage cell lines to study the potential impacts of infiltrating macrophages in the BPH development and found that co-culturing prostate epithelial cells with macrophages promoted migration of macrophages. In a three-dimensional culture system, the sphere diameter of BPH-1 prostate cells was significantly increased during coculture with THP-1 macrophage cells. Mechanism dissection suggested that expression levels of epithelial-mesenchymal transition (EMT) markers, such as N-cadherin, Snail, and TGF-?2, were increased, and administration of anti-TGF-?2 neutralizing antibody during co-culture suppressed the EMT and THP-1-mediated growth of BPH-1 cells, suggesting THP-1 might go through EMT to influence the BPH development and progression. Importantly, we found that modulation of androgen receptor (AR) in BPH-1 and mPrE cells significantly increased THP-1 and RAW264.7 cell migration, respectively, and enhanced expression levels of EMT markers, suggesting that AR in prostate epithelial cells might play a role in promoting macrophage-mediated EMT in prostate epithelial cells. Silencing AR function via an AR degradation enhancer, ASC-J9, decreased the macrophage migration to BPH-1 cells and suppressed EMT marker expression. Together, these results provide the first evidence to demonstrate that prostate epithelial AR function is important for macrophage-mediated EMT and proliferation of prostate epithelial cells, which represents a previously unrecognized role of AR in the cross-talk between macrophages and prostate epithelial cells. These results may provide new insights for a new therapeutic approach to battle BPH via targeting AR and AR-mediated inflammatory signaling pathways. PMID:22915828
Lu, Tianjing; Lin, Wen-Jye; Izumi, Kouji; Wang, Xiaohai; Xu, Defeng; Fang, Lei-Ya; Li, Lei; Jiang, Qi; Jin, Jie; Chang, Chawnshang
Background Benign prostatic hyperplasia (BPH) is a common disease of the aging male population. BPH treatment includes a variety of pharmacological and surgical interventions. The goal of this paper is to review the natural history of BPH, outcomes of pharmacological management, effects on quality of life (QoL), future pharmacotherapies, and associated patient-focused perspectives. Materials and methods Medline searches for the keywords benign prostatic hyperplasia, BPH, alpha blockers, 5 alpha-reductase, and quality of life were performed. Relevant literature was reviewed and analyzed. Results Alpha blockers, 5 alpha-reductase inhibitors, and phytotherapy are the three categories of pharmaceutical interventions currently available for BPH. Various clinical trials have shown that alpha blockers and 5 alpha-reductase inhibitors are safe, efficacious, and improve QoL in patients with BPH. The evidence for phytotherapeutics is not as convincing. The current armamentarium of pharmaceutical interventions are encompassed in these three classes of medications. New pharmacotherapies based on novel mechanisms are on the horizon. Conclusion There are a variety of safe and efficacious medical therapies available for the management of BPH and it is important for the practicing physician to have an understanding of these pharmacotherapies and their potential impact on the patient. There is not enough evidence to make a recommendation regarding phytotherapy use. New classes of drugs for BPH will likely find their way into routine use.
Cambio, Angelo J; Evans, Christopher P
• Laser treatment of benign prostatic hyperplasia has challenged transurethral resection of the prostate (TURP) due to advances in laser technology, better understanding of tissue-laser interactions and growing clinical experience. • Various lasers have been introduced including neodymium: yttrium aluminium garnet (YAG), holmium (Ho):YAG, potassium titanyl phosphate:YAG, thulium(Tm) and diode laser. Based on the different wave-length dependent laser-prostatic tissue interactions, the main techniques are coagulation, vaporization, resection and enucleation. • The present review aims to help urologists to distinguish and to critically evaluate the role of different laser methods in the treatment by using an evidence-based approach. It also details further evidence for use in specific patient groups (in retention, on anticoagulation) and addresses the issues of cost and learning curve. • Coagulation-based techniques have been abandoned; holmium ablation/resection of the prostate has been superseded by the enucleation technique Ho-laser enucleation of the prostate (HoLEP). The short-term efficacy of the emerging laser treatments such as diode and Tm prostatectomy has been suggested by low quality studies. HoLEP and photoselective vaporization of the prostate (PVP) represent valid clinical alternatives to TURP. HoLEP is the most rigorously analysed laser technique with durable efficacy for any prostate size and low early and late morbidity. PVP has grown in acceptance and popularity but long-term results from high quality studies are pending. PMID:21438974
Gravas, Stavros; Bachmann, Alexander; Reich, Oliver; Roehrborn, Claus G; Gilling, Peter J; De La Rosette, Jean
Purpose Laparoscopic simple prostatectomy was recently developed to treat voluminous benign prostatic hyperplasia (BPH). We describe the surgical technique and assess the feasibility of laparoscopic simple prostatectomy through our early experience. Materials and Methods The medical records of 11 patients who underwent laparoscopic simple prostatectomy between March 2008 and January 2010 were retrospectively analyzed. The subjects were limited to the patients who satisfied the following conditions: prostate volume was at least 75 g, acute urinary retention repeatedly occurred or maximal flow rate (Qmax) was at most 10 ml/s, and International Prostate Symptom Score (IPSS) was at least 12. The surgery was performed by the laparoscopic extraperitoneal approach with a transcapsular route. Feasibility was assessed by objective operative parameters (reconversion, operating time, and blood loss) and perioperative complications. Data on short-term follow-up were also available. Results The mean age of the patients was 70.6 years. Mean preoperative prostate-specific antigen and prostate volume were 6.1 ng/ml and 109.3 cc, respectively. Mean operation time was 191.9 minutes and estimated blood loss was 390.9 cc. The resected adenoma weighed on average 72.4 g. No conversion to open surgery was required. Mean preoperative IPSS and quality of life (QoL) scores were 26.86 and 4.86. Mean Qmax, measured before the surgery, was 4.5 ml/s and residual urine was 106 ml. Mean postoperative IPSS and QoL scores were 4.2 and 1.5. After the surgery, mean Qmax was 15.5 ml/s and residual urine was 24.1 ml. Conclusions In the case of voluminous BPH, laparoscopic retropubic simple prostatectomy is expected to be a useful treatment on the condition that the learning curve can be overcome with clinical experience.
Yun, Han Ki; Kwon, Joon Beom; Cho, Sung Ryong
Fifty-three patients with BPH have been evaluated and treated with TMT with a follow-up at 7 months. The prostate was heated\\u000a transcrectally to 42–43°C and the treatment consisted of 5 to 6 sessions. The duration of each session was 60 minutes. The\\u000a urodynamic parameters studied revealed an increase of the maximum flow rate and a decrease of the detrusor opening
E. Liatsikos; K. Dadinis; G. Barbalias
Purpose:Cyclooxygenase-2 (COX-2) is expressed in human BPH tissue and displays either a pro-inflammatory effect or a proliferative effect on prostate cells. The aim of this study is to analyze whether combination therapy with rofecoxib, a COX-2 inhibitor, and finasteride offers an advantage compared to finasteride monotherapy in patients with BPH.
Franco Di Silverio; Cesare Bosman; Monti Salvatori; Luca Albanesi; Laura Proietti Pannunzi; Mauro Ciccariello; Antonio Cardi; Gianfilippo Salvatori; Alessandro Sciarra
Medical therapy for the treatment of benign prostatic hyperplasia (BPH) became an accepted standard of care in the 1990s following the reports of randomized, double-blind, placebo-controlled studies showing that finasteride, a 5-? reductase inhibitor, and terazosin, an ?-blocker, significantly improved lower urinary tract symptoms and increased peak urinary flow rates in men with BPH. This article reviews novel approaches to the pharmacological treatment of BPH.
Benign prostatic hyperplasia (BPH) is a very common condition, related to aging and causing symptoms, called lower urinary tract symptoms. On account of its huge prevalence, it is important for clinicians who are involved in the management of patients with BPH to be aware of the very strict recommendations for BPH evaluation. In this article, we describe the different steps and procedures doctors should follow to evaluate these patients; symptoms and signs of BPH are reviewed, as well as the clinical evaluation steps and examinations available. The basic evaluation of the patients with BPH should include, according to the recommendations of the most relevant international guidelines, lower urinary tract symptoms evaluation with appropriate symptom scores, digital rectal examination, voiding charts, prostate-specific antigen and creatinine measurement, urinalysis, and imaging of the urinary tract. PMID:23244722
Santos Dias, José
Alcohol consumption and cigarette smoking were evaluated in relation to development of benign prostatic hyperplasia (BPH) among 29,386 members of the Health Professionals Follow-up Study. Men who were 40-75 years old in 1986 and free of prior BPH surgery, diagnosed cancer at baseline, and prostate cancer at baseline and during follow-up were followed for incidence of BPH surgery from 1986
Elizabeth A. Plate; Eric B. Rimm; Ichiro Kawachi; Graham A. Coldite; Meir J. Stampfer; Walter C. Willett; Edward Giovannucci
Objectives. To assess the utility of prostate-specific antigen (PSA) as a predictor of prostate volume by characterizing the relationship between prostate volume and serum PSA in men with symptomatic benign prostatic hyperplasia (BPH) and no evidence of prostate cancer, stratified by decade of life.Methods. Placebo-controlled multicenter trials in patients with BPH and a safety study in normal young men provided
Claus G. Roehrborn; Peter Boyle; A. Lawrence Gould; Joanne Waldstreicher
This part of our study presents results of laboratory evaluations in patients with BPH during treatment with prazosin and\\u000a doxazosin. After 72 weeks serum PSA and PAP fell by 40.2% and 82%, respectively. Blood urea nitrogen concentration decreased\\u000a by 28.5% and serum creatinine by 20.8%. The results confirm long-term favourable effects of the therapy of patients with BPH.
S. Dutkiewicz; A. Witeska; K. St?pie?
Benign prostatic hyperplasia (BPH) is the most common proliferative disease of the prostate of men in the United States. The\\u000a histopathology of BPH strongly implicates local paracrine and autocrine growth factors and inflammatory cytokines in its pathogenesis.\\u000a A complex milieu of growth-regulatory proteins includes members of the fibroblast, insulin-like, and transforming growth factor\\u000a families. It appears that these proteins and
M. Scott Lucia; James R. Lambert
To evaluate the role of lasers that allow acute removal of obstructing tissue in the surgical treatment of benign prostatic\\u000a hyperplasia (BPH). A MEDLINE search over the last 6 years focused on randomized trials, large case series and review articles.\\u000a A total of more than 4,000 patients were analyzed with respect to the morbidity and outcome, and the advantages and disadvantages
Rainer M. Kuntz
The 5?-reductase inhibitor dutasteride and the ?(1)-adrenergic receptor antagonist tamsulosin are available as a fixed-dose combination for use in men with symptomatic benign prostatic hyperplasia (BPH) and an enlarged prostate. Dutasteride 0.5?mg/day plus tamsulosin 0.4?mg/day improved lower urinary tract symptoms (LUTS) to a significantly greater extent than dutasteride or tamsulosin alone in men with BPH, moderate to severe LUTS and an increased risk of disease progression, according to the results of the randomized, double-blind, multinational CombAT trial. The mean change from baseline in the total International Prostate Symptom Score was significantly greater with dutasteride plus tamsulosin than with dutasteride or tamsulosin alone after 2 years (primary endpoint) and 4 years of therapy. After 4 years' therapy in the CombAT trial, the time to first acute urinary retention or BPH-related surgery (primary endpoint) significantly favoured men with symptomatic BPH who were receiving dutasteride plus tamsulosin versus those receiving tamsulosin alone, with no significant difference between recipients of dutasteride plus tamsulosin and recipients of dutasteride alone. In the CombAT trial, health-related quality of life and treatment satisfaction were improved to a significantly greater extent with dutasteride plus tamsulosin than with dutasteride or tamsulosin alone. Combination therapy with oral dutasteride plus tamsulosin was generally well tolerated in patients with symptomatic BPH in the CombAT trial. PMID:22550968
Keating, Gillian M
Purpose C-reactive protein (CRP) is a general marker for inflammation and it has been associated with prostate cancer. We hypothesized that a correlation may exist between CRP and prostate cancer in patients undergoing transrectal biopsy of the prostate because of rising prostate-specific antigen (PSA) levels. Materials and Methods From January 2009 to March 2012, we retrospectively reviewed 710 patients who visited our urology department and were diagnosed as having a PSA value over 4.0 ng/mL. Patients with acute infections, rheumatoid arthritis, gout, asthma, chronic lung disease, myocardial infarction, or apoplexy and those who had taken nonsteroidal anti-inflammatory drugs were exempted from the research because these variables could have impacted CRP. After we applied the exclusion criteria, we selected 63 patients with prostate cancer and 140 patients with benign prostatic hyperplasia (BPH). Results A total of 203 patients were observed: 140 patients had BPH, and 63 patients had prostate cancer. Prostate cancer patients were divided into two groups by tumor-node-metastasis classification. The patients below T2 were group A, and those above T3 were group B. The natural logarithm of C-reactive protein (lnCRP) differed between the BPH group and the prostate cancer group. The lnCRP also differed between the BPH group and prostate cancer groups A and B (p<0.05). Conclusions The serum CRP level of the prostate cancer group was higher than that of the BPH group. Inflammation may be correlated with prostate cancer according to the serum CRP level.
Kim, Youngjun; Jeon, Yongseok; Lee, Hana; Lee, Donghyun
Objective: To determine the validity coefficient of the total prostate gland volume as an expression of the transition zone (TZ) volume. To test the hypothesis of hyperinsulinaemia as a causal factor for the development of benign prostatic hyperplasia (BPH).Patients and Methods: Three hundred and seven consecutive patients with lower urinary tract symptoms were studied. A subgroup of 114 patients were
Jan Hammarsten; Benkt Högstedt
A retrospective analysis was made of the treatment results for the last 5 years of 879 patients with benign prostatic hyperplasia (BPH), 214 (24.3%) of whom had undergone transvesical adenomectomy while 665 (75.7%) had undergone transurethral resection (TUR) of the prostate. Adenomectomy had rather high effectiveness but was less safe than endoscopic intervention (higher lethality, more frequent development of myocardial infarction, pulmonary artery thromboembolism, postoperative hemorrhage). Patients operated for BPH are at risk of postoperative urethral stricture and sclerosis of urinary bladder cervix. Prebladder and postoperative stress urine incontinence appear only after open operations in BPH. PMID:15022441
Kamalov, A A; Gushchin, B L; Dorofeev, S D; Komlev, D L; Tokarev, F V; Efremov, E A
Background: To compare the clinical value of the measurement of complex and total PSA in the discrimination between benign prostatic hyperplasia (BPH) and prostate cancer. Methods: In serum samples collected from 166 men with histopathologically proven clinically localized prostate cancer and of 97 men with BPH, total prostate-specific antigen (PSA), complexed PSA and the free to total PSA ratio were
Michael Froehner; Oliver W. Hakenberg; Rainer Koch; Uta Schmidt; Axel Meye; Manfred P. Wirth
Objectives: The exact cause of benign prostatic hyperplasia (BPH) and prostatic carcinoma is unknown. Changes in the level of the trace element zinc (Zn) are known to be associated with the functioning of different organs (breast, colon, stomach, liver, kidney, prostate, and muscle). This study is aimed at estimating and comparing the zinc levels in the prostate tissue, plasma, and urine obtained from patients diagnosed with BPH or prostatic carcinoma. Materials and Methods: The prostate tissue zinc, plasma zinc, and urine zinc/creatinine ratio in BPH, prostate cancer, and normal subjects were measured by atomic absorption spectrophotometry. Results: In prostate carcinoma, the mean tissue zinc was decreased by 83% as compared to normal tissue and in BPH, there was a 61% decrease in mean tissue zinc as compared to normal tissues. Both these values were statistically significant. The plasma zinc in prostate cancer patients showed a 27% decrease (P < 0.01) as compared to controls and 18% decrease (P < 0.01) as compared to BPH. The urine zinc/creatinine (ratio) was significantly increased to 53% in prostate cancer patients, and a 20% significant increase was observed in BPH as compared to normal subjects. Conclusions: It is evident from this study that BPH or prostate carcinoma may be associated with a reduction in the levels of tissue zinc, plasma zinc, and an increase in urine zinc/creatinine.
Christudoss, Pamela; Selvakumar, R.; Fleming, Joseph J.; Gopalakrishnan, Ganesh
Sexual health has significant impact on quality of life among men with benign prostatic hyperplasia (BPH). The degree of sexual\\u000a dysfunction matches the severity of lower urinary tract symptoms (LUTS). Treatment of BPH affects not only LUTS, but sexual\\u000a function as well. Medical, surgical, and minimally invasive therapies differ in their effect on erectile function, ejaculation,\\u000a and sexual satisfaction. Choice
Paul K. Hegarty; Nicholas J. Hegarty; John M. Fitzpatrick
Transurethral resection of the prostate (TURP) remains the gold standard surgical intervention for men with benign prostatic hyperplasia (BPH). However, there are other, newer technologies that have also demonstrated safety and efficacy at least equivalent to that of TURP (e.g., Holmium laser, photoselective vaporization of the prostate). These minimally invasive techniques may be particularly useful for selected patient populations (e.g., those on anticoagulant therapy).
Elhilali, Mostafa M.
Lasers have been given much hype as regards their use in surgical management of benign prostatic hyperplasia (BPH). Transurethral resection of prostate (TURP), especially with its modifications still remains the gold standard treatment for BPH, owing to its efficacy and proven advantages over laser prostatectomy. Cost, unproven long-term durability, steep learning curve, and no advantages of laser prostatectomy over TURP and its modifications, make lasers superfluous in the surgical management of BPH in developing countries.
Gupta, Narmada P.; Anand, Ajay
Benign prostatic hyperplasia (BPH) is one of the most common diseases among elderly men. As the old-age population is increasing recently, it is to our interest to observe the growing BPH within them. In BPH, the dihydrotestosterone (DHT) acts as promotes prostate growth. It inhibits enzyme 5?-reductase that is involved in the conversion of testosterone to the DHT activity which reduces the excessive prostate growth. Through experiments, the effects of Phellius linteus water extract performed on the BPH rats were induced by testosterone treatments. For 12 weeks, Sprague-Dawley rats were treated with testosterone for the induction of BPH. Rats were divided into four experimental groups: the not treated group (N), the testosterone injection and D.W treatment group (TN), the testosterone injection and Phellinus linteus treatment group (TP) and testosterone injection and finasteride treatment group (TF). Prostate weight, volume and weight ratio in the TP group and the TF group were significantly lower than the TN group. Testosterone and DHT levels in the TN group were significantly higher than that of the N group. And the TP group was significantly decreased than that of the TN group. While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation; the TP and TF groups showed trophic symptoms and were lined by flattened epithelial cells, thus, the stromal proliferation is relatively low as compared to the TN group. These suggest that Phellinus linteus water extracts may be an useful remedy for treating the benign prostatic hyperplasia. PMID:23766877
Kim, Yu-Na; Kim, Min-Sun; Chun, Sung-Sik; Choi, Jeong-Hwa
Androgens and estrogens, acting via their respective receptors, are important in benign prostatic hyperplasia (BPH). The goals of this study were to quantitatively characterize the tissue distribution and staining intensity of androgen receptor (AR) and estrogen receptor-alpha (ER?), and assess cells expressing both AR and ER?, in human BPH compared to normal prostate. A tissue microarray composed of normal prostate and BPH tissue was used and multiplexed immunohistochemistry was performed to detect AR and ER?. We used a multispectral imaging platform for automated scanning, tissue and cell segmentation and marker quantification. BPH specimens had an increased number of epithelial and stromal cells and increased percentage of epithelium. In both stroma and epithelium, the mean nuclear area was decreased in BPH relative to normal prostate. AR expression and staining intensity in epithelial and stromal cells was significantly increased in BPH compared to normal prostate. ER? expression was increased in BPH epithelium. However, stromal ER? expression and staining intensity was decreased in BPH compared to normal prostate. Double positive (AR and ER?) epithelial cells were more prevalent in BPH, and fewer double negative (AR and ER?) stromal and epithelial negative cells were observed in BPH. These data underscore the importance of tissue layer localization and expression of steroid hormone receptors in the prostate. Understanding the tissue-specific hormone action of androgens and estrogens will lead to a better understanding of mechanisms of pathogenesis in the prostate and may lead to better treatment for BPH. PMID:23792768
Nicholson, Tristan M; Sehgal, Priyanka D; Drew, Sally A; Huang, Wei; Ricke, William A
Increase of the Prostatic Specific Antigen (PSA) is a non-invasive, sensitive and specific markers for prostatic diseases, including prostatic cancer. However, age-related Benign Prostatic Hyperplasia (BPH), as well as prostatitis, may at the same time alter PSA values. The aim of this study was to evaluate the relationship between ageing and PSA, and whether age-specific upper normal limits of PSA
Mario Bo; Manuel Ventura; Renata Marinello; Simona Capello; Giovanni Casetta; Fabrizio Fabris
The advantages offered by lasers compared to older technologies for endoscopic surgery for symptomatic benign prostate hyperplasia (BPH) are reviewed. Laser treatments for the endoscopic management of patients with bladder outlet obstruction (BOO) resulting from BPH can be divided into three basic techniques. These techniques are vaporisation (removal of tissue), resection of tissue (excision of small chips and subsequent irrigation from bladder) and enucleation (dissection of the adenoma from the surgical capsule and subsequent morcellation). The decision to offer a transurethral laser approach to patients with BPH depends on their comorbidities, the surgeon's expertise with the different procedures, and the availability of the relevant technology. PMID:23780301
Kahokehr, Arman Adam; Gilling, Peter J
Benign prostatic hyperplasia (BPH) is an extremely common condition and represents a major health issue in terms of patient numbers and treatment cost. Traditionally, the choice of treatment has been between watchful waiting and surgery, however, the side effects of surgery lead to reluctance for treatment in many men, other than those with severe symptoms and complications. In the last
Nicholas J. Hegarty; John M. Fitzpatrick
Elevated expression of cyclo-oxygenase (COX)-2 has been found in several human cancers, including prostate adenocarcinoma. To evaluate the potential prognostic role of COX-2 in prostate cancer, we assessed the expression of COX-2 in benign prostatic hyperplasia (BPH) and prostate cancer samples employing immunohistochemistry. COX-2 was over-expressed in 15 out of 18 (83%) prostate cancer samples whereas it was detected in only 22% (4 of 18) paired benign tissues. The intensity of immunostaining correlated with the tumor grading. In addition, COX-2 was expressed in 7 of the 22 (32%) BPH samples examined. The significance a COX-2 expression in the BPH samples is not known at present. This data suggest that COX-2 is over-expressed in prostate cancer and COX-2 inhibitors may be useful in combination chemotherapy or chemoprevention for prostate cancer. PMID:11396201
Lee, L M; Pan, C C; Cheng, C J; Chi, C W; Liu, T Y
The latest technical improvements in the surgical armamentarium are remarkable. In particular, advancements in the urologic field are so exceptional that we could observe the flare-up of robot-assisted laparoscopic radical prostatectomy for prostate cancer and laser prostatectomy for benign prostatic hyperplasia (BPH). Photoselective vaporization of the prostate (PVP) and holmium laser prostatectomy are the most generalized options for laser surgery of BPH, and both modalities have shown good postoperative results. In comparison to transurethral prostatectomy (TURP), they showed similar efficacy and a much lower complication rate in randomized prospective clinical trials. Even in cases of large prostates, laser prostatectomy showed comparable efficacy and safety profiles compared to open prostatectomy. From a technical point of view, PVP is considered to be an easier technique for the urologist to master. Furthermore, patients can be safely followed up in an outpatient clinic. Holmium laser enucleation of the prostate (HoLEP) mimics open prostatectomy because the adenomatous tissue is peeled off the surgical capsule in both procedures. Therefore, HoLEP shows notable volume reduction of the prostate similar to open prostatectomy with fewer blood transfusions, shorter hospital stay, and cost reduction regardless of prostate size. Outcomes of laser prostatectomy for BPH are encouraging but sometimes are unbalanced because safety and feasibility studies were reported mainly for PVP, whereas long-term data are mostly available for HoLEP. We need longer-term randomized clinical data to identify the reoperation rate of PVP and to determine which procedure is the ideal alternative to TURP and open prostatectomy for each patient. PMID:21165192
Son, Hwancheol; Song, Sang Hoon; Paick, Jae-Seung
The transurethral microwave thermotherapy (TUMT) method combines the principles of microwave radiative heating and conductive cooling to destroy tissue within the prostate while preserving the other structures of the lower urinary tract. The method is effective in benign prostatic hyperplasia (BPH), as demonstrated by laboratory and clinical studies. The ease of the 1-hour office treatment, the dramatic symptomatic improvement and reasonable uroflow rates that result, the preservation of sexual function, the apparent safety, and the durability of the result may mean that TUMT will introduce changes in the management of BPH as dramatic as those brought about in lithiasis management by ESWL. PMID:7689386
Devonec, M; Tomera, K; Perrin, P
Symptomatic benign prostatic hyperplasia (BPH) typically occurs in the sixth and seventh decades, and the most frequent obstructive\\u000a urinary symptoms are hesitancy, decreased urinary stream, sensation of incomplete emptying, nocturia, frequency, and urgency.\\u000a Various medications, specifically 5-?-reductase inhibitors and selective ?-blockers, can decrease the severity of the symptoms\\u000a secondary to BPH, but prostatectomy is still considered to be the traditional
Francisco Cesar Carnevale; Alberto Azoubel Antunes; Joaquim Mauricio da Motta Leal Filho; Luciana Mendes de Oliveira Cerri; Ronaldo Hueb Baroni; Antonio Sergio Zafred Marcelino; Geraldo Campos Freire; Airton Mota Moreira; Miguel Srougi; Giovanni Guido Cerri
The medical treatment of benign prostatic hyperplasia (BPH) has its roots in the early 1970s. During this era, the first clinical trials investigating ?-blockade and androgen deprivation therapy were reported for men with clinical BPH. The observation that clinical BPH was improved following administration of both ?-blockers and androgen deprivation therapy supported the evolving paradigm that clinical BPH resulted from dynamic and static pathways. During the past several decades, the evolution of ?-blockers for the treatment of BPH has been impacted by innovations targeted to simplify the administration and improve tolerability while maintaining their effectiveness.
Context: Although benign prostatic hyperplasia (BPH) is an andro- gen-dependent disorder, little is known regarding the influence of serum testosterone levels on sexual or prostate function or clinical response to dutasteride. Objective: The objective of the study was to explore these relation- ships in a large cohort of men treated with dutasteride for BPH. Design, Setting, Patients, and Outcome Measures:
Michael Marberger; Claus G. Roehrborn; Leonard S. Marks; Timothy Wilson; Roger S. Rittmaster
Objective: The aim of the present study was to ascertain the frequency of sexual dysfunction in patients with benign prostatic hyperplasia (BPH) before prostatectomy.Methods: The study population included 131 patients aged 55–74 years (mean 61.4±2.7) with BPH. The patients had been complaining of daytime urgency and nocturia for the last 1–14 years (average 4.5±1.5 years). The diagnosis of BPH was
Jack Baniel; Solomon Israilov; Joseph Shmueli; Ephraim Segenreich; Pinchas M. Livne
The first empirical use of ?1-adrenoceptor antagonists in urology occurred about 25 years ago in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH), or LUTS\\/BPH. Today, many randomized, controlled trials have provided evidence for the efficacy and tolerability of ?1-adrenoceptor antagonists in LUTS\\/BPH, and they are the most frequently used initial treatment option for this
J. Curtis Nickel
Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens and androgen receptor pathways to BPH and use of androgen reducing compounds, such as 5?-reductase inhibitors which block the conversion of testosterone into dihydrotestosterone, are a component of the standard of care for men with LUTS attributed to an enlarged prostate. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17?. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; however, new models are needed to genetically dissect estrogen regulated molecular mechanisms involved in BPH. More work is needed to identify estrogens and associated signaling pathways in BPH in order to target BPH with dietary and therapeutic SERMs.
Nicholson, Tristan M.; Ricke, William A.
The prevalence of prostatic intraepithelial neoplasia (PIN) in men who underwent surgery for benign prostatic hyperplasia\\u000a (BPH) before and after the Chernobyl nuclear accident was studied. BPH samples were obtained by adenomectomy from 45 patients\\u000a operated in 1984 before the accident (Group I), and 47 patients from the low contaminated Kiev City (Group II) and 76 from\\u000a high contaminated area
Alexander F Vosianov; Alina M Romanenko; Larisa B Zabarko; Béla Szende; Ching Y Wang; Steven Landas; Gabriel P Haas
Background Benign prostatic hyperplasia (BPH), a common condition among older men, confers its morbidity through potentially bothersome lower urinary tract symptoms. Treatments for BPH include drugs such as alpha-adrenergic receptor blockers and 5-alpha reductase inhibitors, minimally invasive therapies that use heat to damage or destroy prostate tissue, and surgery including transurethral resection of the prostate. Complementary and alternative medicines are
Jeannette Lee; Gerald Andriole; Andrew Avins; E David Crawford; Harris Foster; Steven Kaplan; Karl Kreder; John Kusek; Andrew McCullough; Kevin McVary; Sreelatha Meleth; Michael Naslund; J Curtis Nickel; Leroy Nyberg; Claus Roehrborn; O. Dale Williams; Michael Barry
Benign prostate hyperplasia (BPH) is a common disease in elderly men. Although it is a non-malignant disease, it has a significant detrimental impact on the quality of life in patients with late-stage disease. Owing to the lack of specific markers, diagnosis of early-stage BPH has been proven unsuccessful. Recently, using two-dimensional electrophoresis, we identified a group of prostatic secretory proteins
K Xu; M-T Ling; X Wang; Y-C Wong
Abstract Objective. There are limited data on whether there is an association between nocturia, benign prostatic hyperplasia (BPH) and endothelial dysfunction. The aim of the present study was to evaluate whether there is an association between nocturia and endothelial dysfunction in patients with BPH. Material and methods. Forty-two men with a diagnosis of BPH and 42 age-matched controls were enrolled. All patients were assessed for frequency and duration of nocturia, and prostate volume, completed the International Prostate Symptom Score (IPSS) questionnaire, and underwent brachial flow-mediated dilatation (FMD) evaluation. Results. There was a negative correlation between FMD and frequency of nocturia (r = -0.879, p < 0.0001). Moreover, there was a negative correlation between duration of nocturia and FMD (r = -0.890, p < 0.0001). In addition, FMD was significantly decreased in the BPH group compared with the control group (6.0 ± 0.09 to 7.8 ± 0.10%) (p = 0.0001). Conclusion. In patients with BPH, nocturia is associated with endothelial dysfunction and may be an insidious risk factor for cardiovascular disease. PMID:23323759
Inci, Mehmet; Sarli, Bahadir; Davarci, Mursel; Yalcinkaya, Fatih Rustu; Rifaio?lu, Murat Mehmet; Davran, Ramazan; Arica, Secil; Motor, Sedat; Demirba?, Onur
Objective: To review the existing evidence regarding the efficacy and safety of medical therapy for lower urinary tract symptoms (LUTS) indicative of benign prostatic hyperplasia (BPH). To assess randomised controlled trials investigating the six ?–adrenergic receptor antagonists (?–blockers), prazosin, alfuzosin, indoramin, terazosin, doxazosin, and tamsulosin, that benefit patients by relaxing prostatic smooth muscle, and the anti–androgen, finasteride, that mediates its
G. M. Clifford; R. D. T. Farmer
Benign prostatic hyperplasia (BPH) and prostate cancer (CaP) are major sources of morbidity in older men. Management of these disorders has evolved considerably in recent years. This article provides a focused overview of BPH and CaP management aimed at primary care physicians. Current literature pertaining to BPH and CaP is reviewed and discussed. The management of BPH has been influenced by the adoption of effective medical therapies; nonetheless, surgical intervention remains a valid option for many men. This can be accomplished with well-established standards such as transurethral resection of the prostate or with minimally invasive techniques. Prostate cancer screening remains controversial despite the recent publication of two large clinical trials. Not all prostate cancers necessarily need to be treated. Robot-assisted prostatectomy is a new and increasingly utilised technique for CaP management, although open radical retropubic prostatectomy is the oncological reference standard. The ageing of the population of the developed world means that primary care physicians will see an increasing number of men with BPH and CaP. Close collaboration between primary care physicians and urologists offers the key to successful management of these disorders. PMID:21070524
Sausville, J; Naslund, M
Patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTSs) have a considerably higher prevalence of cardiovascular disease (CVD) than the general population in old age. Many hypotheses have been created to explain traditional clinical risk factors of CVD, including age, male gender, cigarette smoking, inheritance, high blood pressure (BP), obesity, elevated fasting plasma glucose, diabetes mellitus, dyslipidemia, decreased physical activity and metabolic syndrome; or nontraditional risk factors such as oxidative stress, inflammation, vascular calcification, malnutrition, homocysteine and genetic variation. Although these risk factors are important in CVD pathophysiology and clinical presentation, there is still no single theory sufficient to provide an adequate explanation for all the properties of CVD. We speculate that by causing nocturia-induced sleep disturbances, BP variability, increased sympathetic activity, non-dipping BP variations; BPH may be an insidious risk factor for CVD. Benign prostate hyperplasia may be related to increased BP, coronary ischemic hearth disease or other cardiovascular pathologic conditions. This attention on BPH may produce a new approach to the diagnosis and treatment of CVD. Although the underlying mechanisms are still exactly unclear, further prospective randomized controlled studies are needed to identify if patients with BPH/LUTS is higher risk for CVD. PMID:19359054
Karatas, Omer Faruk; Bayrak, Omer; Cimentepe, Ersin; Unal, Dogan
Benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS due to BPH. Alpha-adrenergic receptor blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit early onset of efficacy with regard to both symptoms and flow rate improvement, and this is clearly demonstrated in placebo-controlled trials with extensions out to five years. These agents have been shown to prevent symptomatic progression of the disease. The aim of this article is to offer a critical review of the current literature on silodosin, formerly known as KMD-3213, a novel alpha-blocker with unprecedented selectivity for ?(1A)-adrenergic receptors, as compared with both ?(1B)- and ?(1D) -adrenoceptors, exceeding the selectivity of all currently used ?(1)-blockers, and with clinically promising effects. PMID:21116335
Rossi, Maxime; Roumeguère, Thierry
Benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS due to BPH. Alpha-adrenergic receptor blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit early onset of efficacy with regard to both symptoms and flow rate improvement, and this is clearly demonstrated in placebo-controlled trials with extensions out to five years. These agents have been shown to prevent symptomatic progression of the disease. The aim of this article is to offer a critical review of the current literature on silodosin, formerly known as KMD-3213, a novel alpha-blocker with unprecedented selectivity for ?1A-adrenergic receptors, as compared with both ?1B- and ?1D -adrenoceptors, exceeding the selectivity of all currently used ?1-blockers, and with clinically promising effects.
Rossi, Maxime; Roumeguere, Thierry
ObjectiveThis prospective study quantified cytokine and chemokine levels in seminal plasma of patients with chronic prostatitis\\/chronic pelvic pain syndrome (CP\\/CPPS) and benign prostatic hyperplasia (BPH), to evaluate inflammatory mediators as possible surrogate markers for diagnosis and treatment efficacy.
Giuseppe Penna; Nicola Mondaini; Susana Amuchastegui; Selene Degli Innocenti; Marco Carini; Gianluca Giubilei; Benedetta Fibbi; Enrico Colli; Mario Maggi; Luciano Adorini
Prostate enlargement and function is under the dual control of androgens and intraprostatic growth factors. They regulate, in con- cert, prostate cell proliferation and apoptosis. An increased signaling of both growth factors and androgens are supposed to underlie benign prostate hyperplasia (BPH), one of the more common disorders of the aging male. Since, in clinical practice, androgen ablation resulted in
CLARA CRESCIOLI; MARIO MAGGI; GABRIELLA BARBARA VANNELLI; MICHAELA LUCONI; ROBERTO SALERNO; TULLIO BARNI; MASSIMO GULISANO; GIANNI FORTI; MARIO SERIO
Eviprostat has been used as a non-hormonal and non-neuropharmacological treatment for benign prostatic hyperplasia (BPH) in\\u000a Japan. We evaluated the clinical efficacy of Eviprostat in patients with symptomatic BPH and the anti-inflammatory effect\\u000a of this drug was investigated by retrospective evaluation of TUR specimens. Clinically, Eviprostat subjectively relieved obstructive\\u000a symptoms of BPH. Objective improvements were also demonstrated by ultrasonographic evaluation
M. Ishigooka; T. Hashimoto; S. Hayami; M. Tomaru; T. Nakada; K. Mitobe
The renin-angiotensin system (RAS) is present in the human prostate and may be activated in benign prostatic hyperplasia (BPH), possibly contributing to the patho- physiology of this disorder by enhancing local sympathetic tone and cell growth. The functional role of the RAS in the prostate, however, is unknown. The present study was undertaken to determine whether angiotensin (Ang) II enhances
M E Fabiani; M Sourial; W G Thomas; C I Johnston; A G Frauman
Prostatic Adenocarcinoma (PA) and Benign Prostatic Hyperplasia (BPH) have their etiology not fully understood mainly in glycidic aspects. Glycan changes are associated with cell alterations where glycosylation is carried out by glycosyltransferases, such as fucosyltransferases (FUTs). These enzymes catalyze the insertion of L-fucose residues in a variety of glycan structures often in the final stage of glycosylation. The present study aimed to investigate the expression of FUT3 and FUT6 in PA and BPH as well as to correlate immunostaining of these transferases with PA clinic-histopathologic data. The FUT3 and FUT6 expressions were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded biopsies of PA (n=40) and BPH (n=40). FUT3 and FUT6 showed a high expression in both prostatic diseases, especially FUT6. FUT6 was more immunoexpressed in PA cases than the FUT3 (p<0.0001) as well as in BPH cases but in a not significant way (p=0.0661). Besides, FUT3 was more expressed in BHP lesion than in PA cases (p<0.0001). Our study presented a new data about FUT3 and FUT6 expression in PA and BPH, revealing high FUT6 expression in both lesions and FUT3 overexpression in BHP in relation to PA, proposing that this enzyme could be a promising biomarker for benign prostate alterations. PMID:23836950
de Albuquerque Vasconcelos, Juliana Lúcia; de Almeida Ferreira, Steffany; de Lima, Amanda Lucena Rosendo; de Melo Rêgo, Moacyr Jesus Barreto; Bandeira, Ana Rosa Galdino; de Lima Bezerra Cavalcanti, Carmelita; de Melo Lira, Mariana Montenegro; Beltrão, Eduardo Isidoro Carneiro
OBJECTIVE: To define primary care physicians' (PCPs) practices in managing patients with benign prostatic hyperplasia (BPH),\\u000a and to compare these practices to portions of the Agency for Health Care Policy and Research BPH guideline and urologists'\\u000a practices. DESIGN: Mail survey. PARTICIPANTS: Nationwide random sample of PCPs and urologists, selected from the American\\u000a Medical Association Registry. METHODS: Initial mailing, postcard reminder,
Mary McNaughton Collins; Michael J. Barry; Lin Bin; Richard G. Roberts; Joseph E. Oesterling; Floyd J. Fowler
Considering the epidemiologic impact of benign prostatic hyperplasia (BPH), the use of minimally invasive surgery in the treatment\\u000a of this condition is one of the main ambitions of contemporary urology. Compared with the prevalence of BPH and LUTS in elderly\\u000a men, only a small percentage of patients requires surgery for indications such as renal insufficiency, chronic retention,\\u000a and infection. The
András Hoznek; Clément-Claude Abbou
The economic burden of benign prostatic hyperplasia (BPH) on our health care system is significant and likely to continue to grow given the burgeoning elderly population. Coincident with the rising number of annual physician office visits and expenditures for BPH has been a dramatic shift in the disease’s management, from surgical to medical care. However, long-term cost data call into question the appropriateness of medical therapy as the initial treatment approach for all men with BPH, particularly those with moderate to severe symptoms. Although there has been a paradigm shift away from traditional BPH surgery, there has been renewed interest in the treatment of BPH with novel surgical techniques and minimally invasive surgeries. The economics of surgical interventions for BPH are discussed.
Hollingsworth, John M; Wei, John T
Benign prostatic hyperplasia (BPH) is the leading cause of lower urinary tract symptoms among the aging male population. Epidemiological, pathophysiological and clinical studies indicate that many of these men also suffer from declining sexual function, especially those undergoing treatment for their BPH-related urinary symptoms. Although urinary symptoms and quality of life may improve with BPH therapy, the resulting effects on sexual function vary by medical, surgical and minimally invasive approaches and have not been consistently reported. As comprehensive, validated instruments to measure male sexual function are now available for routine use in the clinical setting, urologists and primary care providers caring for patients with BPH have the opportunity to monitor both urinary and sexual function before, during and after BPH therapy. Herein, we describe the relationship between BPH and its treatments on male sexual function, the role of new measures for sexual functioning and opportunities for future work to improve the care of men suffering from both maladies.
Skolarus, TA; Wei, JT
Prostatic artery embolization (PAE) has emerged as an alternative to surgical treatments for benign prostatic hyperplasia (BPH). Patient selection and refined technique are essential for good results. Urodynamic evaluation and magnetic resonance imaging are very important and technical limitations are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The use of small-diameter hydrophilic microcatheters is mandatory. Patients can be treated safely by PAE with low rates of side effects, reducing prostate volume with clinical symptoms and quality of life improvement without urinary incontinence, ejaculatory disorders, or erectile dysfunction. A multidisciplinary approach with urologists and interventional radiologists is essential to achieve better results. PMID:23903785
Carnevale, Francisco C; Antunes, Alberto A
Benign prostatic hyperplasia (BPH) is the most commonly occurring neoplastic disease in the aging human male. Currently, surgical treatment of BPH is the primary therapeutic method. However, due to surgical complications, less invasive methods of treatment are desirable. In recent years, thermal coagulation of the hyperplastic prostate by a laser has received a considerable amount of attention. Nevertheless, the optimum laser irradiation parameters that lead to a successful and safe treatment of BPH have not been determined. This dissertation studies the physics of laser coagulation of prostate from both basic science and practical perspectives. Optical properties of prostatic tissue are determined over a spectrum of wavelengths. Knowledge of these properties allows for selection of appropriate laser wavelengths and provides a basis for performing dose equivalency studies among various types of lasers. Furthermore, knowledge of optical properties are needed for development of computer simulation models that predict the extent of thermal injury during laser irradiation of prostate. A computer model of transurethral heating of prostate that can be used to guide the clinical studies in determining an optimum dosimetry is then presented. Studies of the effects of non-laser heating devices, optical properties, blood perfusion, surface irrigation, and beam geometry are performed to examine the extent of heat propagation within the prostate. An in vitro model for transurethral laser irradiation of prostate is also presented to examine the effects of an 810 nm diode laser, thermal boundary conditions, and energy deposition rate during Nd:YAG laser irradiation. Results of these studies suggest that in the presence of laminar irrigation, the convective boundary condition is dominated by thermal diffusion as opposed to the bulk motion of the irrigation fluid. Distinct phases of thermal events are also identified during the laser irradiation. The in vivo studies of transurethral laser irradiation of prostate in canine models are also performed to search for an optimum dosimetry that will result in a maximum zone of coagulation necrosis.
Many patients who present to their healthcare provider with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) will also have erectile dysfunction (ED), and vice versa. Although ?-adrenergic receptor blockers and 5-?-reductase inhibitors are highly effective in treating BPH-associated LUTS, these agents have sexual adverse effects that cause many men to discontinue therapy. The discovery of nitric oxide as a major factor in the mechanism of erection has led to the development of new drugs for ED, including the phosphodiesterase (PDE) inhibitors. Preliminary data support the theory that inhibition of PDE isoenzymes in the prostate may improve LUTS due to BPH through relaxation of prostatic smooth muscle. Further studies of PDE inhibitors in men with ED and BPH-associated LUTS are indicated.
Roehrborn, Claus G
The aryl hydrocarbon receptor (AHR) is an evolutionarily conserved ligand activated transcription factor best known for its role in mediating toxic responses to dioxin-like environmental contaminants. However, AHR signaling has also emerged as an active participant in processes of normal development and disease progression. Here, we review the role of AHR signaling in prostate development and disease processes, with a particular emphasis on benign prostatic hyperplasia (BPH). Inappropriate AHR activation has recently been associated with a decreased risk of symptomatic BPH in humans and has been shown to impair prostate development and disrupt endocrine signaling in rodents. We highlight known physiological responses to AHR activation in prostate and other tissues and discuss potential mechanisms by which it may act in adult human prostate to protect against symptomatic BPH.
Mehta, Vatsal; Vezina, Chad M.
Pharmaceutical preparations are commonly used for benign prostate hyperplasia. This article reviews the current understanding of the natural history of the condition and the literature regarding medical treatment.
Connolly, Stephen S; Fitzpatrick, John M
Background: Kaempferia parviflora rhizome is used as a folk medicine in Thailand for the treatment of various symptoms. In the present study, the inhibitory activities of extract from K. parviflora rhizome against 5?-reductase (5?R) were subjected. Furthermore, the effects of the extract from K. parviflorar hizome in benign prostate hyperplasia (BPH) were studied using the model mice. Materials and Methods: Preparations of extracts from the rhizomes of K. parviflora, Curcuma zedoaria and Zingiber officinale, and methoxyflavones isolated from K. parviflora was used for 5?R inhibition assay. The effects of K. parviflora extract on growth suppression for the prostates and seminal vesicles were performed based on the Hershberger's method. The K. parviflora extract was administered to castrated mice for 14 days. Results: K. parviflora extract showed more potent inhibitory activity on 5?R than C. zedoaria and Z. officinale extracts. The active principles were identified as 3,5,7,3’,4’-pentamethoxyflavone and 5,7,3’,4’-tetramethoxyflavone by activity guided fractionation. Furthermore, K. parviflora extract suppressed the weights of prostates and seminal vesicles in BPH model rats by daily administration for 14 days. Conclusion: These results indicate that K. parviflora extract can be a promising agent for the treatment of BPH.
Murata, Kazuya; Hayashi, Hirotaka; Matsumura, Shinichi; Matsuda, Hideaki
Gastrin releasing-peptide (GRP) is a potent growth factor in many malignancies. Benign prostatic hyperplasia (BPH) is a progressive age-related proliferation of glandular and stromal tissues; various growth factors and inflammatory processes are involved in its pathogenesis. We have demonstrated that potent antagonists of GRP inhibit growth of experimental human tumors including prostate cancer, but their effect on models of BPH has not been studied. Here, we evaluated the effects of GRP antagonist RC-3940-II on viability and cell volume of BPH-1 human prostate epithelial cells and WPMY-1 prostate stromal cells in vitro, and in testosterone-induced BPH in Wistar rats in vivo. RC-3940-II inhibited the proliferation of BPH-1 and WPMY-1 cells in a dose-dependent manner and reduced prostatic cell volume in vitro. Shrinkage of prostates was observed after 6 wk of treatment with RC-3940-II: a 15.9% decline with 25 ?g/d; and a 18.4% reduction with 50 ?g/d (P < 0.05 for all). Significant reduction in levels of proliferating cell nuclear antigen, NF-??/p50, cyclooxygenase-2, and androgen receptor was also seen. Analysis of transcript levels of genes related to growth, inflammatory processes, and signal transduction showed significant changes in the expression of more than 90 genes (P < 0.05). In conclusion, GRP antagonists reduce volume of human prostatic cells and lower prostate weight in experimental BPH through direct inhibitory effects on prostatic GRP receptors. GRP antagonists should be considered for further development as therapy for BPH. PMID:23359692
Rick, Ferenc G; Abi-Chaker, Andrew; Szalontay, Luca; Perez, Roberto; Jaszberenyi, Miklos; Jayakumar, Arumugam R; Shamaladevi, Nagarajarao; Szepeshazi, Karoly; Vidaurre, Irving; Halmos, Gabor; Krishan, Awtar; Block, Norman L; Schally, Andrew V
Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer, an equal number of cases of benign prostatic hyperplasia (BPH) and an equal number of apparently healthy control subjects. The three groups were matched for age and town of residence in the greater Athens area. Steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1 (IGF-1) were measured in duplicate by radioimmunoassay in a specialized US centre. Statistical analyses were performed using multiple logistical regression. The results for IGF-1 in relation to prostate cancer and BPH were adjusted for demographic and anthropometric factors, as well as for the other measured hormones. There was no relation between IGF-1 and BPH, but increased values of this hormone were associated with increased risk of prostate cancer; an increment of 60 ng ml(-1) corresponded to an odds ratio of 1.91 with a 95% confidence interval of 1.00-3.73. There was also some evidence for an interaction between high levels of testosterone and IGF-1 in relation to prostate cancer. This finding suggests that, in addition to testosterone, IGF-1 may increase the risk of prostate cancer in humans.
Mantzoros, C. S.; Tzonou, A.; Signorello, L. B.; Stampfer, M.; Trichopoulos, D.; Adami, H. O.
Background Serum prostate specific antigen (PSA) concentrations lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We identified 5 autoantibody signatures to specific cancer targets which might be able to differentiate prostate cancer from BPH in patients with increased serum PSA. Methods To identify autoantibody signatures as biomarkers, a native antigen reverse capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nanoparticle slides to capture native antigens from prostate cancer cells. Prostate cancer patient serum samples (n=41) and BPH patient samples (collected starting at the time of initial diagnosis) with a mean follow-up of 6.56 y without the diagnosis of cancer (n=39) were obtained. One hundred micrograms of IgGs were purified and labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined. Results Using our microarray platform, we identified autoantibody signatures capable of distinguishing between prostate cancer and BPH. The top 5 autoantibody signatures were TARDBP, TLN1, PARK7, LEDGF/PSIP1, and CALD1. Combining these signatures resulted in an AUC of 0.95 (sensitivity of 95% at 80% specificity) compared to AUC of 0.5 for serum concentration PSA (sensitivity of 12.2% at 80% specificity). Conclusion Our preliminary results showed that we were able to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with increased serum PSA.
O'Rourke, Dennis J.; DiJohnson, Daniel A.; Caiazzo, Robert J.; Nelson, James C.; Ure, David; O'Leary, Michael P.; Richie, Jerome P.; Liu, Brian C.-S.
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 pa- tients less than 40 yr of age and 10 age- and
PAOLO MARZULLO; DIEGO FERONE; STEFANO SPIEZIA; GAETANA CERBONE; VALERIA MARINO; ANTONELLA DI SARNO; BARTOLOMEO MEROLA; GAETANO LOMBARDI
Purpose Clinical benign prostatic hyperplasia (BPH) is primarily diagnosed based on a diverse array of progressive lower urinary tract symptoms (LUTS) and is likely distinct from histological BPH, which is detected by the presence of non-malignant proliferation of prostate cells but may or may not be associated with symptoms. Pharmacological management of LUTS has emerged as an effective initial treatment for clinical BPH due to the introduction of new drug therapies shown to be effective in recent large clinical trials. Despite advances in symptom management and research into BPH pathology, diagnostic strategies for prediction of BPH progression and response to drug modalities are lacking and questions remain as to the molecular differences underlying clinical (symptomatic) versus histological (non-symptomatic) BPH. Materials and Methods As part of the Medical Therapy of Prostatic Symptoms (MTOPS) clinical trial, which demonstrated the effectiveness of combination drug therapy in slowing BPH progression, an archive of biological specimens linked to clinical data were collected for future profiling of disease pathology and changes associated with response to drug therapy. The MTOPS Prostatic Samples Analysis (MPSA) Consortium was established to identify and validate molecular markers that may better define BPH-related pathologies, identify risk for progression of LUTS, and predict response to drug therapy, using this MTOPS archive. The cooperating MPSA Biomarker Discovery Sites and Pathology Coordinating Center employ diverse methodologies and scientific approaches and unique expertise in addressing the goals of the consortium. Results To date the MPSA has identified a number of promising biomarkers and other molecular and cellular changes associated with BPH. Conclusions These findings and ongoing consortium discovery efforts have the potential to provide a greater understanding of the defects underlying disease pathology and may lead to the development of early and more effective pharmacological treatment strategies for BPH.
Mullins, Chris; Lucia, M. Scott; Hayward, Simon W.; Lee, Jeannette Y.; Levitt, Jonathan M.; Lin, Victor K.; Liu, Brian C.-S.; Chinnaiyan, Arul M.; Rubin, Mark A.; Slawin, Kevin; Star, Robert A.; Getzenberg, Robert H.
The recent introduction of high-power 200-W diode laser vaporization of the prostate has resulted in new interest in minimally\\u000a invasive surgery for the treatment of benign prostatic hyperplasia (BPH). Although clinical reports are still limited, experimental\\u000a ex vivo or in vivo models have demonstrated that this laser device offers improved ablative and hemostatic abilities. Some\\u000a preliminary clinical results have proven
Po-Hui Chiang; Chien-Hsu Chen
The dual 5?-reductase inhibitor, dutasteride has been shown to suppress serum dihydrotestosterone (DHT) by >90%. In the present study, the effect of dutasteride 0.5 mg\\/day on intraprostatic DHT levels was investigated. In this multicenter, double-blind trial, 43 men with benign prostatic hyperplasia (BPH) scheduled to undergo transurethral resection of the prostate (TURP) were randomized to receive dutasteride, 0.5 mg\\/day or
R Wurzel; P Ray; K Major-Walker; J Shannon; R Rittmaster
Benign prostatic hyperplasia (BPH) is a very common condition in ageing men and causes considerable morbidity. Although great strides have been made recently, important issues remain under-researched and poorly understood. We have conducted a survey on a representative sample of Italian males to investigate the knowledge and opinion on prostate, to estimate the self-reported prevalence and intensity of BPH and LUTS (low urinary tract symptoms) and to evaluate the performance of the International Prostate Symptom Score (I-PSS) in a population-based sample. Trained interviewers administered a standardized questionnaire to a representative random sample of 671 Italian men aged 50 years and over, between May and June 2000. Univariate and multivariate statistical techniques were used to estimate the prevalence of relevant events, and the associations with selected variables. Only half of responders were able to identify the reason for prostate enlargement, less than one-third recently had spoken with a doctor, and only 8.6% had had a rectal examination. Further, 13.7% (95% confidence interval (CI) 11.1-16.3%) had ever been told they had BPH, with less than half of them receiving surgery for BPH. About 19% reported moderate-severe I-PSS. Both self-reported BPH and severe-moderate LUTS increased significantly with age ( -value <0.01). As to the I-PSS performance, we documented in a community-based sample that it is reliable and valid. Results of the multivariate analysis suggest that, in addition to age, a person's knowledge that they have BPH and a poor perception of health status are the main variables associated with the probability of moderate-severe LUTS. In conclusion, this community-based survey documents that Italian males have a poor knowledge and perception of prostate-related conditions and do not adequately care about them and, thus, do not seek medical attention. These facts notwithstanding, urological conditions such as BPH are common and may largely affect an individual's life. Our findings might help in the design and implementation of effective interventions to improve people's knowledge and understanding of prostate and change their attitudes towards medical care. PMID:12394245
Apolone, G; Cattaneo, A; Colombo, P; La Vecchia, C; Cavazzuti, L; Bamfi, F
Last decade several new treatment modalities for minimal invasive therapy of benign prostatic hyperplasia have been developed, both ablative and non-ablative. In this review the authors describe the different techniques and clinical studies of bipolar transurethral resection of the prostate (TURP), transurethral resection in saline (TURis), the different laser therapies for the prostate, transurethral microwave thermotherapy (TUMT), high intensity focused ultrasound (HIFU), transurethral needle ablation (TUNA), hot water induced thermotherapy (WIT), prostatic stents, intraprostatic ethanol injections and botulinum toxin A injections. The different bipolar systems and photoselective vaporisation might replace the ''gold standard'', monopolar TURP, in the near future. The holmium laser enucleation of the prostate is also a real challenger of the ''gold standard'', but the technique is difficult to learn. The TUMT definitively found its place as alternative to TURP, especially because it can be performed in an outpatient setting without the need of anaesthesia. Therefore it is also suitable in patients at high risk. The long-term data on TUNA and HIFU is disappointing and therefore these treatment modalities did not stand the test of time. WIT seemed to be a promising therapy, but durability is questionable. Intraprostatic ethanol injections are safe and effective in small series, but larger series are needed to confirm its efficacy. Intraprostatic botulinum toxin A injections are the first treatment of BPH to target both the increase in smooth muscle tone (dynamic component) and the excessive growth (static component) of BPH. This approach of BPH is very promising but more studies with long-term follow up are needed. PMID:19773727
Van Hest, P; D'Ancona, F
Objectives. To evaluate the long-term effects of finasteride on symptoms, acute urinary retention (AUR), and the need for benign prostatic hyperplasia (BPH)-related surgery in relationship to baseline symptom severity.Methods. A total of 3040 men with BPH were treated for 4 years with finasteride or placebo. The changes from baseline in symptoms and the incidence of BPH-related surgery and AUR were
Steven Kaplan; Dennis Garvin; Patricia Gilhooly; Max Koppel; Richard Labasky; Richard Milsten; Pratap Reddy; Steven Rosenberg; David Sussman; Charles White; Michael Lee; Frances Pappas; Joanne Waldstreicher
Inflammation is a common finding in benign prostatic hyperplasia (BPH) and may be classified as acute, chronic active or chronic inactive prostatitis. The aim of the present study was to localise the different types of inflammatory cells in prostatic lesions to determine the sequence of events in the cellular reaction. We have carried out immunohistological characterisation of the inflammatory cells, using CD45RO and CD3 antibodies to detect T-lymphocytes, CD20 antibodies to detect B-lymphocytes, CD68 to detect macrophages, kappa and lambda immunoglobulin light chains, and antibodies against prostate specific antigen (PSA) and prostate specific acid phosphatase (PSAP). Macrophages accumulated in the lumen and glandular epithelial layers of damaged prostatic glands and were found in the periglandular cuff of inflammatory cells in acute and chronic active prostatitis. Lymphocytes also accumulated in large numbers in the glandular epithelial layers and around the glands, indicating an association with macrophages. B-lymphocytes were scanty, if at all present, in acute and chronic active prostatitis, but were prominent within well-organised follicle centres in chronic active prostatitis. Cells positive for light chains were few and scattered in prostatic tissue. PSA and PSAP activity was lost in recently damaged prostatic glandular epithelium and reappeared only in regenerating secretory epithelium, indicating leakage as a result of damage. We suggest that the initial response to prostatic injury is cellular, and probably related to leakage into the periglandular tissues of PSA, PSAP and other antigenic molecules normally present in prostatic secretion. Macrophages respond, followed by recruitment of T-lymphocytes which participate in the inflammatory response and accumulate around the damaged glands. B-cell activity appears to be a late event. PMID:9842422
Anim, J T; Udo, C; John, B
Objective To assess the association of selected occupational exposures with risk of prostate cancer and with risk of benign prostatic hyperplasia (BPH). Methods This population?based case–control study recruited 606 men with a diagnosis of confirmed prostate cancer, 400 men who had undergone their first prostatectomy for BPH and 471 male controls randomly selected from the electoral roll between 1 August 2001 and 1 October 2002 in Western Australia. ?2 tests and logistic regressions were used for univariate and multivariate analyses to investigate the association of the two outcomes with occupational exposure to pesticides, fertilisers, metals, wood dust, oils, diesel exhaust and polyaromatic hydrocarbons (PAHs). Results Exposure to toxic metals at a non?substantial level increased the risk of BPH (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.1 to 1.84) and led to a non?significant excess risk of prostate cancer (OR 1.25, 95% CI 0.96 to 1.61). Non?significant excess risks were observed for prostate cancer after exposure to oils other than mineral oil (OR 1.54, 95% CI 0.95 to 2.51) and for BPH after exposure to PAHs (OR 1.20, 95% CI 0.91 to 1.58). A non?statistically significant protective effect for prostate cancer was seen after exposure to organophosphate pesticides (OR 0. 69, 95% CI 0.43 to 1.12). No other associations were found for either prostate cancer or BPH and no dose–response relationships were seen for the exposures investigated. Conclusions These results do not provide evidence that any of the occupational factors examined are risk factors for either prostate cancer or BPH.
Fritschi, L; Glass, D C; Tabrizi, J S; Leavy, J E; Ambrosini, G L
Aim:To explore the interaction between bladder compliance (BC) and bladder outflow obstruction (BOO) in men with benign prostatic hyperplasia (BPH) using cross-sectional and longitudinal studies.Methods:A total of 181 men with BPH were recruited, and 100 of them were followed for one year. Cystometry was performed in a standing or a sitting position with 30 mL\\/min infusion. BC was manually corrected
Li-Min Liao; Werner Schaefer
Lepidium meyenii (maca) is a plant that grows exclusively above 4000 m in the Peruvian central Andes. Red maca (RM) extract significantly reduced prostate size in rats with benign prostatic hyperplasia (BPH) induced by testosterone enanthate (TE). Zinc is an important regulator of prostate function. This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE. Also, the study attempted to determine the best marker for the effect of RM on sex accessory glands. Rats treated with RM extract from day 1 to day 14 reversed the effect of TE administration on prostate weight and zinc levels. However, RM administered from day 7 to day 14 did not reduce the effect of TE on all studied variables. Finasteride (FN) reduced prostate, seminal vesicle and preputial gland weights in rats treated with TE. Although RM and FN reduced prostate zinc levels, the greatest effect was observed in TE-treated rats with RM from day 1 to day 14. In addition, prostate weight and zinc levels showed the higher diagnosis values than preputial and seminal vesicle weights. In conclusion, RM administered from day 1 to day 14 reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE. Also, this experimental model could be used as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products based on maca. PMID:21762188
Gonzales, C; Leiva-Revilla, J; Rubio, J; Gasco, M; Gonzales, G F
Objectives Numerous inflammatory diseases display elevated IL-8, and most are associated with a reactive stroma. IL-8 expression is also elevated in benign prostatic hyperplasia (BPH) yet little is known about reactive stroma in BPH. Whether a reactive stroma response exists in BPH, whether this correlates with elevated IL-8, and whether IL-8 can induce a reactive stroma phenotype has not been determined. This study was designed to specifically address these issues. Methods Normal prostate transition zone (NPTZ) tissue and BPH specimens, as identified by BCM Pathology, were examined by quantitative immunohistochemistry to correlate IL-8, smooth muscle ?-actin (?-SMA), vimentin, calponin, and tenascin-C. In addition, human prostate stromal cell cultures were used to evaluate the effect of IL-8 on expression of reactive stroma biomarkers. Results BPH nodules exhibited elevated epithelial IL-8 immunoreactivity, and this correlated with elevated ?-SMA, reduced calponin and altered deposition of tenascin-C, relative to NPTZ tissue (p<0.05). Multiple vimentin-positive prostate stromal fibroblast cultures were induced by IL-8 to also co-express ?-SMA and tenascin-C, typical of a reactive stroma myofibroblast phenotype. Conclusions These data show that BPH reactive stroma is fundamentally different from normal prostate fibromuscular stroma, and is typified by the emergence of a reactive stroma myofibroblast phenotype. This reactive stroma pattern correlated spatially with elevation of IL-8 in adjacent epithelium. Additionally, IL-8 induced expression of myofibroblast markers in human prostate fibroblasts in vitro. These studies suggest that IL-8 acts as a regulator of BPH reactive stroma and is therefore a potential therapeutic target.
Schauer, Isaiah G.; Ressler, Steven J.; Tuxhorn, Jennifer A.; Dang, Truong D.; Rowley, David R.
The aim of the study was to elucidate influence of alpha1A adrenoblocker tamsulosine (omnique) on ischemic heart disease (IHD) symptoms in patients with benign prostatic hyperplasia (BPH). As shown by Holter monitoring, 15 patients of group 1 having IHD, BPH and impaired miction, demonstrated ECG changes before voiding (ST depression, higher rate of supraventricular and ventricular extrasystoles); 28 patients of group 2 had ECG changes unrelated to miction. Subjective and objective effects were registered in a month in all the patients. ECG parameters improved in 11 and 20 patients of group 1 and 2, respectively. Patients without ECG improvement had severe cardial pathology (three-vessel affection of the coronary arteries, effort angina of a high functional class, cardiac failure). Thus, miction impairment due to BPH aggravate IHD. Early administration of tamsulosine (omnique) for BPH improves the course of concomitant IHD in 72% patients. PMID:15776825
Aliaev, Iu G; Fiev, D N; Kopylov, F Iu; Lokshin, K L; Demidko, Iu L; Svet, A V; Vinarov, A Z; Syrkin, A L
To develop a novel gene therapeutic modality for the effective treatment of benign prostatic hyperplasia (BPH), we investigated the properties of toxic gene therapy utilizing prostate-specific antigen (PSA) promoter driving herpes simplex virus thymidine kinase (HSV-TK) suicide gene to induce highly selective molecular ablation of epithelial cells with minimal systemic toxicity in canine prostate. Replication-defective recombinant adenoviral vectors containing HSV-TK
H S Park; J Cheon; H Y Cho; Y H Ko; J H Bae; D G Moon; J J Kim
Aging & Health A to Z Prostate Diseases Basic Facts & Information What are Prostate Diseases? The prostate—one of the components of a man's sex organs—is a ... out anything serious. The Most Common Types of Prostate Diseases Benign prostatic hyperplasia (BPH) Prostatitis Prostate cancer ...
Two-micron (thulium) laser resection of the prostate-tangerine technique (TmLRP-TT) is a transurethral procedure that uses a thulium laser fiber to dissect whole prostatic lobes off the surgical capsule, similar to peeling a tangerine. We recently reported the primary results. Here we introduce this procedure in detail. A 70-W, 2-?m (thulium) laser was used in continuous-wave mode. We joined the incision by making a transverse cut from the level of the verumontanum to the bladder neck, making the resection sufficiently deep to reach the surgical capsule, and resected the prostate into small pieces, just like peeling a tangerine. As we resected the prostate, the pieces were vaporized, sufficiently small to be evacuated through the resectoscope sheath, and the use of the mechanical tissue morcellator was not required. The excellent hemostasis of the thulium laser ensured the safety of TmLRP-TT. No patient required blood transfusion. Saline irrigation was used intraoperatively, and no case of transurethral resection syndrome was observed. The bladder outlet obstruction had clearly resolved after catheter removal in all cases. We designed the tangerine technique and proved it to be the most suitable procedure for the use of thulium laser in the treatment of benign prostatic hyperplasia (BPH). This procedure, which takes less operative time than standard techniques, is safe and combines efficient cutting and rapid organic vaporization, thereby showing the great superiority of the thulium fiber laser in the treatment of BPH. It has been proven to be as safe and efficient as transurethral resection of the prostate (TURP) during the 1-year follow-up.
Histotripsy was evaluated as a non-invasive BPH treatment. The prostates of 21 canine subjects were targeted with one of three histotripsy doses. Prostates were harvested immediately, 7 days, or 28 days after treatment and assessed for changes. Lower treatment doses were found to produced scattered cellular disruption and hemorrhage that was sometimes reversible. Higher doses perforated the urethra and produced cavities in the glandular prostate that healed to leave an enlarged urinary channel.
Hall, Timothy L.; Hempel, Chris R.; Lake, Alison M.; Kieran, Kathy [University of Michigan Department of Urology, Ann Arbor, MI (United States); Ives, Kim; Cain, Charles A. [University of Michigan Department of Biomedical Engineering, Ann Arbor, MI (United States); Fowlkes, J. Brian [University of Michigan Department of Radiology, Ann Arbor, MI (United States); University of Michigan Department of Biomedical Engineering, Ann Arbor, MI (United States); Roberts, William W. [University of Michigan Department of Urology, Ann Arbor, MI (United States); University of Michigan Department of Biomedical Engineering, Ann Arbor, MI (United States)
In search for the new polypeptides responsible for energy homeostasis which are also involved in regulating the growth and function of the human prostate, we assessed the expression of orexins (OXs) and of orexin receptors (OXRs) in human normal prostate and in benign prostatic hyperplasia (BPH). Conventional RT-PCR revealed the expression of OXR2 in all studied samples obtained either from normal prostates or BPH ones while neither preproorexin (ppOX)nor OXR1 mRNA were detected. In adenomatous prostates, expression levels of OXR2 were 30- to 40-fold higher compared to controls. Western blot analysis demonstrated the presence of OXR2 protein in the studied samples and its expression levels were 4-fold higher in tissue samples from BPH. In normal glands, presence of OXR2-like immunoreactivity was found in the apical parts of epithelial cells as well as in smooth muscle cells of the stroma. Immunostaining for OXR2 was more intense in sections obtained from BPH. Immunohistochemistry did not detect the expression of OXR1-like protein. OXA serum concentrations were lowered in BPH patients (mean ± SE 56±4 ng/ml, n=12; P<0.01) and unaltered in prostate cancer (79±7 ng/ml, n=18) compared to the controls (69±2 ng/ml, n=16). On the contrary, serum OXB levels were similar in all studied groups of patients. We thus have demonstrated the mRNA and protein expression of OXR2, but not of ppOX and OXR1 in both normal and BPH human prostate glands. We also demonstrated notable up-regulation of OXR2 in benign prostatic hyperplasia, an alteration accompanied by lowered serum OXA concentrations. These findings suggest that both OXA and OXR2 may be involved in the pathogenesis and/or maintenance of BPH. PMID:21186399
Malendowicz, Witold; Szyszka, Marta; Ziolkowska, Agnieszka; Rucinski, Marcin; Kwias, Zbigniew
We measured immunoreactive EGF and TGF alpha in prostate tissue extracts obtained from 19 patients with benign prostatic hyperplasia (BPH) and 19 with cancer of the prostate (CaP). Whilst both BPH and CaP expressed EGF (BPH = 195.61 +/- 19.94 ng g-1 protein; CaP = 235.60 +/- 24.45 ng g-1 protein) and TGF alpha (BPH = 92.57 +/- 7.60 ng g-1 protein; CaP = 100.73 +/- 15.47 ng g-1 protein) in equal concentrations, the levels of EGF in any tissue extract were on average twice those of TGF alpha. Furthermore analysis of the individual growth factor data revealed a direct correlation between EGF and TGF alpha in both BPH (r = 0.72, P < 0.001) and CaP (r = 0.69, P < 0.001). When the tumours were classified according to their Gleason score, a slight but significant increase in growth factor concentrations was noted as the tumour became less differentiated. We also measured the concentrations of testosterone and dihydrotestosterone (DHT) in prostate extracts with a view of elucidating the relationship between androgen and growth factors in this gland. There was a small positive correlation only between testosterone and EGF (r = 0.62, P < 0.05) and testosterone and TGF alpha (r = 0.61, P < 0.05) in CaP. The absence of any similar correlation in BPH where DHT becomes the predominant hormone may suggest an indirect role for testosterone in the regulation of growth factor production.
Yang, Y.; Chisholm, G. D.; Habib, F. K.
This review summarizes the concept that the neo-formation of ductal-acinar architecture in the pathogenesis of benign prostatic hyperplasia (BPH) is due to the reactivation of embryonic inductive activity by BPH stroma, an idea enunciated by John McNeal. The concept is the synthesis of McNeal's astute pathological inference based upon developmental biology and supported by the mesenchyme-epithelial interaction studies. In a broader context, McNeal's concept of framing epithelial pathogenesis in terms of developmental biological principals has been extended more recently into the field of carcinogenesis under the umbrella of tumor microenvironment.
Cunha, Gerald R.; Ricke, William A.
Estrogen has important roles in the initiation and development of benign prostatic hyperplasia (BPH). Regulators of the estrogen receptor (ER) are tissue- and cell-specific. We evaluated the effect of estrogen antagonist, raloxifene (Ral), on the prevention and treatment of BPH by investigating its effect on the proliferation of two different prostate cell lines: a stromal cell line, WPMY-1, and a benign prostatic hyperplasia epithelial cell line, BPH-1. We additionally evaluated its effect on prostatic hyperplasia induced by estrogen and androgen in a rat model. The effect of Ral on the prevention of prostatic hyperplasia was analyzed by haematoxylin and eosin staining and quantitative immunohistochemistry (IHC) for proliferating cell nuclear antigen and alpha-smooth muscle actin. In vitro and in vivo, tamoxifen (Tam), another anti-estrogen drug, and finasteride (Fin), a drug for the clinical treatment of BPH, served as efficacy controls. The in vitro data showed that neither Ral nor Tam alone affected the proliferation of WPMY-1 and BPH-1, but both antagonized the effect of oestradiol in promoting the proliferation of the two cells. Results from the IHC staining of the rat prostates indicated that, similar to Tam and Fin, Ral inhibited the proliferation of stromal cells in vivo. Interestingly, in contrast to Tam, both Ral and Fin inhibited the proliferation of epithelial cells. Furthermore, Ral treatment much strongly decreased the number of prostatic acini and the surrounding layers of smooth muscle cells than Fin (P < 0.05). Our data showed for the first time that Ral may have a role in the response of the rat prostate to selective ER modulators. PMID:20473319
Yang, Rui; Ma, Yu-Xia; Chen, Lin-Feng; Zhou, Ying; Yang, Zhan-Po; Zhu, Yan; Du, Xiao-Ling; Shi, Jian-Dang; Ma, Hong-Shun; Zhang, Ju
Estrogen has important roles in the initiation and development of benign prostatic hyperplasia (BPH). Regulators of the estrogen receptor (ER) are tissue- and cell-specific. We evaluated the effect of estrogen antagonist, raloxifene (Ral), on the prevention and treatment of BPH by investigating its effect on the proliferation of two different prostate cell lines: a stromal cell line, WPMY-1, and a benign prostatic hyperplasia epithelial cell line, BPH-1. We additionally evaluated its effect on prostatic hyperplasia induced by estrogen and androgen in a rat model. The effect of Ral on the prevention of prostatic hyperplasia was analyzed by haematoxylin and eosin staining and quantitative immunohistochemistry (IHC) for proliferating cell nuclear antigen and ?-smooth muscle actin. In vitro and in vivo, tamoxifen (Tam), another anti-estrogen drug, and finasteride (Fin), a drug for the clinical treatment of BPH, served as efficacy controls. The in vitro data showed that neither Ral nor Tam alone affected the proliferation of WPMY-1 and BPH-1, but both antagonized the effect of oestradiol in promoting the proliferation of the two cells. Results from the IHC staining of the rat prostates indicated that, similar to Tam and Fin, Ral inhibited the proliferation of stromal cells in vivo. Interestingly, in contrast to Tam, both Ral and Fin inhibited the proliferation of epithelial cells. Furthemore, Ral treatment much strongly decreased the number of prostatic acini and the surrounding layers of smooth muscle cells than Fin (P < 0.05). Our data showed for the first time that Ral may have a role in the response of the rat prostate to selective ER modulators.
Yang, Rui; Ma, Yu-Xia; Chen, Lin-Feng; Zhou, Ying; Yang, Zhan-Po; Zhu, Yan; Du, Xiao-Ling; Shi, Jian-Dang; Ma, Hong-Shun; Zhang, Ju
ObjectivesTo elucidate the clinical significance of detrusor overactivity (DO) that is probably due to C-fiber activation caused by bladder outlet obstruction (BOO), we examined the responses to the ice water test (IWT) in patients with benign prostatic hyperplasia (BPH) and assessed the results with reference to the clinical manifestations and urodynamic findings.
Akihide Hirayama; Kiyohide Fujimoto; Yoshihiro Matsumoto; Seiichiro Ozono; Yoshihiko Hirao
To review key trials of monotherapy and combination therapy of alpha(1)-adrenergic receptor antagonists (alpha(1)-ARAs), 5alpha-reductase inhibitors (5alphaRIs) and anti-muscarinic agents in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). To assess the safety and efficacy of combination therapies for LUTS associated with BPH, a search of the MEDLINE and Cochrane databases (1976-2008) was conducted for relevant trials and reviews using the terms benign prostatic hyperplasia, lower urinary tract symptoms, alpha(1)-adrenergic receptor antagonists, 5alpha-reductase inhibitors, anti-muscarinics, anticholinergics, combination therapy, alfuzosin, doxazosin, tamsulosin, terazosin, dutasteride, finasteride, tolterodine, flavoxate, propiverine, oxybutynin, erectile dysfunction, sildenafil, vardenafil and tadalafil. Data from the Medical Therapy of Prostatic Symptoms (MTOPS) study indicated a role for long-term use of alpha(1)-ARAs and 5alphaRIs in combination. In the MTOPS study, combination therapy with the alpha(1)-ARA doxazosin and the 5alphaRI finasteride was significantly more effective than either component alone in reducing symptoms (P=0.006 vs doxazosin monotherapy; P<0.001 vs finasteride monotherapy) and in lowering the rate of clinical progression (P<0.001 vs either monotherapy). These findings were confirmed by the 2-year preliminary results of the Combination of Avodart and Tamsulosin study. In this study, combination therapy of the alpha(1)-ARA tamsulosin and the 5alphaRI dutasteride resulted in a significantly greater decrease in International Prostate Symptom Score (IPSS) when compared with either monotherapy. Several recent trials have studied the efficacy of combining alpha(1)-ARAs and anti-muscarinic agents in the treatment of BPH. These studies have found this combination to result in statistically significant benefits in quality of life scores, patient satisfaction, urinary frequency, storage symptoms and IPSS scores. Studies have not shown an increased risk of urinary retention associated with the use of anti-muscarinics in a highly select cohort of men with BPH. The available data suggest that combination therapy can be beneficial in the treatment of BPH and associated LUTS. The greatest efficacy for the alpha(1)-ARA and 5alphaRI combination was shown in patients with larger prostate size and more severe symptoms. The combination of alpha(1)-ARAs and 5alphaRIs appears to prevent disease progression in these patients. The combination of alpha(1)-ARAs with anti-muscarinic agents is useful for relieving symptoms of bladder outlet obstruction and detrusor overactivity. Theoretic concerns regarding the risk of acute urinary retention have been refuted in several recent clinical trials; however, it must be noted that the patients in these trials were a highly select cohort of men. Men with overactive bladder and BPH who are not receiving adequate alleviation of symptoms from the first-line alpha(1)-ARAs may benefit from the addition of an anti-muscarinic agent. PMID:19002123
Greco, K A; McVary, K T
The epidemiology of benign prostatic hyperplasia (BPH) and male lower urinary tract symptoms (LUTS) has evolved considerably\\u000a during the past several years. The term LUTS describes a distinct phenotype and allows for a broad epidemiologic description\\u000a of urinary symptoms at a population level. Although it is becoming the preferred term for studying urinary symptoms in populations,\\u000a LUTS remains interconnected with
J. Kellogg Parsons
BackgroundCombination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and prostatic enlargement.
Claus G. Roehrborn; Paul Siami; Jack Barkin; Ronaldo Damião; Kim Major-Walker; Indrani Nandy; Betsy B. Morrill; R. Paul Gagnier; Francesco Montorsi
Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) commonly affect older men. These bothersome symptoms can lead to a decreased quality of life. Currently, two classes of drugs - ?-adrenergic blockers and 5?-reductase inhibitors - are prescribed to treat LUTS secondary to BPH. Due to their different mechanisms of action, these medications work in a synergistic manner. Trials of combination therapy have been conducted to assess its effect compared with monotherapy. Current data support combination therapy in men with moderately enlarged prostates and moderate to severe symptoms. PMID:23024707
Chughtai, Bilal; Elterman, Dean S; Lee, Richard; Te, Alexis E; Kaplan, Steven A
Current treatments for benign prostatic hyperplasia (BPH) include watchful waiting, medical therapy, and interventional procedures. The post-surgical complication profile and the early discontinuation of medical therapy are significant drawbacks of the established approach and stimulate the search for less-invasive approaches. Our aim is to provide a comprehensive review all available literature on prostatic urethral lift (PUL), presenting an overview of safety, indications, surgical technique and results of the procedure, and to evaluate the potential role it could play in the treatment of BPH. A comprehensive search was conduct on PubMed and Scopus database to identify original articles in English dealing with PUL without any limit to publication date. Keywords used were prostatic urethral lift, urethral lifting, Urolift, benign prostatic hyperplasia and minimally invasive therapy. The PUL seems to offer a better IPSS improvement when compared to medical therapy, but the result is inferior when compared to surgical therapy. Published studies report an absence of degradation of erectile or ejaculatory function after treatment, which appears a noteworthy benefit of PUL. Additional advantages of the PUL are a better complication profile in comparison to other surgical therapies and the use of a local anesthesia, sometimes without postoperative catheterization. The PUL, a novel, minimally invasive treatment option for men affected by BPH, presents a promising potential although it is clear that PUL is not a substitute for traditional ablative surgical approach, as this procedure requires a scrupulous selection of the patient. PMID:23794125
Larcher, Alessandro; Broglia, Luigi; Lughezzani, Giovanni; Mistretta, Francesco; Abrate, Alberto; Lista, Giuliana; Fossati, Nicola; Sangalli, Mattia; Kuefner, Dana; Cestari, Andrea; Buffi, Nicolomaria; Lazzeri, Massimo; Guazzoni, Giorgio; Montorsi, Francesco
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BACKGROUND AND PURPOSE Inflammation plays a key role in the development of benign prostatic hyperplasia (BPH). Eicosanoids derived from the COX and 5-lipoxygenase (5-LOX) pathways are elevated in the enlarging prostate. Flavocoxid is a novel flavonoid–based ‘dual inhibitor’ of the COX and 5-LOX enzymes. This study evaluated the effects of flavocoxid in experimental BPH. EXPERIMENTAL APPROACH Rats were treated daily with testosterone propionate (3 mg·kg?1 s.c.) or its vehicle for 14 days to induce BPH. Animals receiving testosterone were randomized to receive vehicle (1 mL·kg?1, i.p.) or flavocoxid (20 mg·kg?1, i.p.) for 14 days. Histological changes, eicosanoid content and mRNA and protein levels for apoptosis-related proteins and growth factors were assayed in prostate tissue. The effects of flavocoxid were also tested on human prostate carcinoma PC3 cells. KEY RESULTS Flavocoxid reduced prostate weight and hyperplasia, blunted inducible expression of COX-2 and 5-LOX as well as the increased production of PGE2 and leukotriene B4 (LTB4), enhanced pro-apoptotic Bax and caspase-9 and decreased the anti-apoptotic Bcl-2 mRNA. Flavocoxid also reduced EGF and VEGF expression. In PC3 cells, flavocoxid stimulated apoptosis and inhibited growth factor expression. Flavocoxid-mediated induction of apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-FMK, in PC3 cells, suggesting an essential role of caspases in flavocoxid-mediated apoptosis during prostatic growth. CONCLUSION AND IMPLICATIONS Our results show that a ‘dual inhibitor’ of the COX and 5-LOX enzymes, such as flavocoxid, might represent a rational approach to reduce BPH through modulation of eicosanoid production and a caspase-induced apoptotic mechanism.
Altavilla, D; Minutoli, L; Polito, F; Irrera, N; Arena, S; Magno, C; Rinaldi, M; Burnett, BP; Squadrito, F; Bitto, A
The Proportion of Prostate-specific Antigen (PSA) Complexed to 1Antichymotrypsin Improves the Discrimination between Prostate Cancer and Benign Prostatic Hyperplasia in Men with a Total PSA of 10 to 30 g\\/L
Background: The aim of this study was to assess the diagnostic accuracy of the proportion of prostate-spe- cific antigen (PSA) complexed to 1-antichymotrypsin (PSA-1ACT:PSA ratio) in the differential diagnosis of prostate cancer (CaP) and benign prostatic hyperplasia (BPH) in men with total PSA of 10 -30 g\\/L. Methods: We used our immunoassays (ELISAs) for total PSA and PSA-1ACT complex to
Manuel Martinez; Francisco Espana; Montserrat Royo; Silvia Navarro; Amparo Estelles; Justo Aznar; Cesar D. Vera; Juan F. Jimenez-Cruz
BACKGROUND. We investigated whether peptides involved in cellular proliferation and apoptosis, (insulin-like growth factor I (IGFI) and its major binding protein (insulin-like growth factor binding protein 3)), predicted risk of benign prostate hyperplasia (BPH). METHODS. We conducted a nested-case-control study in the placebo arm of the prostate cancer prevention trial (PCPT). Cases (n ¼ 727) were men with surgical or
Marian L. Neuhouser; Jeannette Schenk; Yoon Ju Song; Catherine M. Tangen; Phyllis J. Goodman; Michael Pollak; David F. Penson; Ian M. Thompson; Alan R. Kristal
Benign prostatic hyperplasia is the most common of all neoplasms. The most common treatment is prostatectomy, but other available therapies include androgen antagonists, ?-adrenergic blockers, anticholinergic agents, prostate dilation with a ballon, and urethral stents. Prostatectomy is likely to remain the standard of care for the foreseeable future because it is safe and much more effective than all other current and experimental forms of therapy.
Skepasts, Peter K.; Lee, Laurence M.
Benign prostatic hyperplasia (BPH) is a complex disease that is progressive in many men. BPH is commonly associated with bothersome lower urinary tract symptoms; progressive disease can also result in complications such as acute urinary retention (AUR) and BPH-related surgery. It is therefore important to identify men at increased risk of BPH progression to optimise therapy. Several factors are associated with progression, including age and prostate volume (PV). Serum prostate-specific antigen level is closely correlated with PV, making it useful for determining the risk of BPH progression. Medical therapy is the most frequently used treatment for BPH. 5-alpha-reductase inhibitors impact the underlying disease and decrease PV; this results in improved symptoms, urinary flow and quality of life, and a reduced risk of AUR and BPH-related surgery. Alpha-blockers achieve rapid symptom relief but do not reduce the overall risk of AUR or BPH-related surgery, presumably because they have no effect on PV. Combination therapy provides greater and more durable benefits than either monotherapy and is a recommended option in treatment guidelines. The Combination of Avodart® and Tamsulosin (CombAT) study is currently evaluating the combination of dutasteride with tamsulosin over 4 years in a population of men at increased risk of BPH progression. A preplanned 2-year analysis has shown sustained symptom improvement with combination therapy, significantly greater than with either monotherapy. CombAT is also the first study to show benefit in improving BPH symptoms for combination therapy over the alpha-blocker, tamsulosin, from 9 months of treatment.
Emberton, M; Cornel, E B; Bassi, P F; Fourcade, R O; Gomez, J M F; Castro, R
The declining level of androgen during aging, associated with an inclining level of estrogen, has been hypothesized to be important in the development of benign prostatic hyperplasia (BPH). Within physiologic range, increasing estrogen levels can stimulate prostate to develop and permanently increase prostate size. As an estrogenic endocrine disruptor, bisphenol A (BPA) might be stimulatory to prostate development. We further hypothesized that low dose BPA could induce hyperplasia prostate to proliferate and aggravate the symptom of BPH in male SD rats. BPH was induced by testosterone and then treated with BPA (10, 30, or 90 ?g/kg, i.g., daily), 17?-estradiol (E(2); 50.0 ?g/kg, s.c., daily), or vehicle for 4 weeks. We found that weight and volume in rats treated with low dose BPA (10 ?g/kg) was higher than that of model control, and BPA significantly increased the relative weight of prostate (p < 0.01). For prostate lobes, BPA 10 ?g/kg/day significantly increased relative weight of ventral prostate (VP), weight and relative weight of dorsolateral prostate (DLP) (p < 0.05). And histopathology results showed that height of epithelial cell (HEC) of VP and DLP in BPA group were significantly higher than that of model control (p < 0.01). BPA could also decrease testosterone level and increase prostate-specific antigen level. E(2) treatment also showed an obvious effect on relative weight of VP and DLP, HEC, and hormone levels. We concluded that environment exposure to low dose of BPA may induce prostate to proliferate and aggravate testosterone-induced benign hyperplasia prostate in rats. PMID:21415097
Wu, Jian-Hui; Jiang, Xiu-Rong; Liu, Gui-Ming; Liu, Xiang-Yun; He, Gui-Lin; Sun, Zu-Yue
Purpose The objective of this study was to report the experience acquired at the Seoul National University Hospital with Holmium Laser Enucleation of Prostate (HoLEP), combined with mechanical morcellation for symptomatic benign prostatic hyperplasia (BPH). Methods A retrospective review was performed on the clinical data of 309 consecutive patients who underwent HoLEP at our institution between July 2008 and June 2010. All patients were evaluated preoperatively for prostate volume by transrectal ultrasound, maximum urinary flow rate (Qmax), International Prostate Symptoms Score (IPSS) and quality of life (QoL) score. Peri- and postoperative parameters were evaluated and patients were followed-up at 1-, 3-, 6-, and 12- months with the aforementioned investigations. Results The patients' mean age was 68.3 (±6.5) years and mean prostate volume was 55.6 (±23.6) mL. Mean enucleation time was 56.2 (±25.1) minutes, mean morcellation time was 11.3 (±9.5) minutes, and the mean resected weight of the prostate was 20.8 (±16.9) g. The mean catheter indwelling period was 1.9 (±1.7) days and mean hospital stay was 2.9 (±1.5) days. Significant improvement was noted in Qmax, IPSS, and QoL at the 1-year follow-up compared with baseline (P<0.01). At 1 month 17.2% of patients complained of irritative urinary symptoms, which were typically self-limiting within 3 months. Transient stress incontinence was reported in 15.2% of patients. No patient experienced persistent obstructive symptoms that required reoperation. Conclusions Our study showed that HoLEP is a safe and effective therapeutic modality for BPH.
Bae, Jungbum; Choo, Minsoo; Park, Ji Hyun; Oh, Jin Kyu; Paick, Jae-Seung
Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays in the treatment of male LUTS and clinical BPH are the ?(1)-adrenergic receptor antagonists. Silodosin is a new ?(1)-adrenergic receptor antagonist that is selective for the ?(1A)-adrenergic receptor. By antagonizing ?(1A)-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. Since silodosin has greater affinity for the ?(1A)-adrenergic receptor than for the ?(1B)-adrenergic receptor, it minimizes the propensity for blood pressure-related adverse effects caused by ?(1B)-adrenergic receptor blockade. In the clinical studies, patients receiving silodosin at a total daily dose of 8 mg exhibited significant improvements in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving placebo. Silodosin showed early onset of efficacy for both voiding and storage symptoms. Furthermore, long-term safety of silodosin was also demonstrated. Retrograde or abnormal ejaculation was the most commonly reported adverse effect. The incidence of orthostatic hypotension was low. In conclusion, silodosin, a novel selective ?(1A)-adrenergic receptor antagonist, was effective in general and without obtrusive side effects. This review provides clear evidence in support of the clinical usefulness of silodosin in the treatment of LUTS associated with BPH. PMID:21753871
Yoshida, Masaki; Kudoh, Junzo; Homma, Yukio; Kawabe, Kazuki
Purpose. To assess the efficacy and safety of intraprostatic injection of two botulinum neurotoxin type A (BoNT-A) doses for the treatment of benign prostatic hyperplasia (BPH). Materials and Methods. Men with symptomatic BPH who failed medical treatment were randomized to receive 100?U or 200?U of BoNT-A into the prostate. The International Prostatic Symptom Score (IPSS), maximum flow rate (Qmax), post-void residual volume (PVR), PSA levels and prostate volume before injection and after 3 and 6 months were evaluated. Adverse events were compared between the groups. Results. Thirty four patients were evaluated, including 17 in the BoNT-A 100?U group and 17 in the BoNT-A 200?U group. Baseline characteristics were similar in both groups. Both doses produced significant improvements in IPSS, Qmax and PVR after 3 and 6 months and both doses promoted comparable effects. Prostate volume was affected by 200?U BoNT-A injection only after 6 months of treatment. PSA levels were significantly affected in the 100?U group only after 6 months of treatment. In the 200?U group, PSA levels were significantly decreased after 3 and 6 months. The complication rate was similar in both groups. Conclusions. Efficacy and safety of both BoNT-A doses are similar for BPH treatment in the short term followup.
Arnouk, Rene; Suzuki Bellucci, Carlos Henrique; Stull, Roberto Benatuil; de Bessa Junior, Jose; Malave, Cesar Augusto; Gomes, Cristiano Mendes
Benign prostatic hyperplasia (BPH) is the most common form of prostate disease in middle-aged and elderly men, and leads to severe impairment later in life. Despite its significant impact on public health, the underlying cause of BPH is yet to be determined. This hypothesis proposes a new causal factor for BPH. Applying concepts of dynamics of fluids to the process of urination it could be stated that a turbulent urinary flow through the passage of the urethra. The turbulent urinary flow in the urethra applies pressure and stretch forces to the surrounding tissue. This stimulus repeated over time and coupled with age-related changes of the urethral tissue could contribute to the development of BPH. In support of this hypothesis, several mechanotransduction studies have shown that vibration and pressure forces applied to different cell tissues can provoke cellular and molecular changes. Another supportive data is the presence of the hyperplasic reaction surrounding the urethra specifically located in the transition zone, the only zone where BPH develops. It is crucial to identify causal factors to understanding the disease and to determine effective primary prevention strategies. Future studies of the dynamics of fluids in the urethra are warranted. The finding of significant forces transmitted to the periurethral tissue from a turbulent urinary flow could give us the clue to the underlying cause of BPH. If this hypothesis proves to be valid there are several primary prevention measures that could be implemented to impede the development of BPH. Educational intervention measures in younger populations to avoid frequent urinary retention and active urination (process of forcing the urine through the urethra at a high velocity) could be considered. Studies of the impact of turbulence in the standing vs. sitting position during urination in men should also be considered. PMID:16764996
Martinez-Borges, Anibal R
Objectives. To study the efficacy and safety of a new transurethral microwave thermotherapy device (the Urowave) in the treatment of men with clinical benign prostatic hyperplasia (BPH) in a randomized, double-blind, sham-controlled trial.Methods. A total of 220 patients (mean age 66.2 years) with clinical BPH, an American Urological Association symptom index (AUA SI) of 13 points or more, and a
Claus G Roehrborn; Glenn Preminger; Phil Newhall; John Denstedt; Hassan Razvi; L. Joseph Chin; Aaron Perlmutter; Winston Barzell; Willet Whitmore; Ralph Fritzsch; Jeffrey Sanders; Scott Sech; Sean Womack
Insulin-like growth factor-I (IGF-I) plays an important role in prostate growth, hyperplasia, and carcinogenesis. Circulating IGF-I levels may be modulated by a genetic cytosine-adenine (CA) repeat polymorphism in the promoter region of IGF-I. The association of the polymorphism with the risk of prostate cancer and benign prostatic hyperplasia (BPH) was explored in 303 patients with prostate cancer, 219 patients with BPH and 262 controls. The number of CA repeats ranged from 15 to 22 in case and control subjects. The 19-CA-repeat allele (19-allele) was more frequently observed in both the prostate cancer and BPH patients compared with the controls (prostate cancer versus control: P<0.001; BPH versus control: P=0.001). Compared with non-carriers of the 19-allele, men homo-zygous for the 19-allele had a significantly increased risk of prostate cancer [age-adjusted odds ratio (aOR) = 3.36, 95% confidence intervals (CI) = 1.30-8.67, P=0.012] or BPH (aOR = 3.53, 95% CI = 1.32-9.46, P=0.012), and those heterozygous for the 19-allele also had an intermediate increased risk of prostate cancer (aOR = 1.78, 95% CI = 1.25-2.53, P=0.001) or BPH (aOR = 1.66, 95% CI = 1.14-2.43, P=0.009). A gene dosage effect for the aORs was found with an increasing number for the 19-allele (P<0.001 in prostate cancer and P=0.001 in BPH). No significant association was found between the presence of the 19-allele and the tumor stage and grade at the time of diagnosis. In conclusion, the 19-allele of IGF-I appears to increase the risk of prostate cancer and BPH with a gene dosage effect in the Japanese population. PMID:15586244
Tsuchiya, Norihiko; Wang, Lizhong; Horikawa, Yohei; Inoue, Takamitsu; Kakinuma, Hideaki; Matsuura, Shinobu; Sato, Kazunari; Ogawa, Osamu; Kato, Tetsuro; Habuchi, Tomonori
From 1993 to 2010, we have treated 156 patients benign prostatic hyperplasia (BPH) and 1,052 patients localized prostate cancer high-intensity focused ultrasound (HIFU). Four different HIFU devices, SonablateR-200, SonablateR-500, SonablateR-500 version 4 and Sonablate® TCM, have been used for this study. Clinical outcome of HIFU for BPH did not show any superior effects to transurethral resection of the prostate, laser surgery or transurethral vapolization of the prostate. However, HIFU appears to be a safe and minimally invasive therapy for patients with localized prostate cancer, especially low- and intermediate-risk patients. The rate of clinical outcome has significantly improved over the years due to technical improvements in the device.
BACKGROUND: Benign prostatic hyperplasia (BPH) affects aging men. Combined therapy with antagonists of growth hormone-releasing hormone (GHRH) and of luteinizing hormone-releasing hormone (LHRH or GnRH) induces prostate shrinkage in rat models. We investigated the mechanisms of action of this combination on cell cycle traverse and expression of prostatic genes. METHODS: Effects of GHRH antagonist, JMR-132 (40 microg\\/day), the LHRH antagonist,
F. G. Rick; A. V. Schally; N. L. Block; A. Abi-Chaker; A. Krishan; L. Szalontay
Purpose We aimed to determine the treatment of choice criteria for benign prostatic hyperplasia (BPH) by analyzing the factors causing alpha-adrenergic receptor blocker (?-blocker) monotherapy failure. Materials and Methods This retrospective study enrolled 129 patients with BPH who were prescribed an ?-blocker. Patients were allocated to a transurethral resection of prostate (TURP) group (after having at least a 6-month duration of medication) and an ?-blocker group. We compared the differences between the two groups for their initial prostate volume, serum prostate-specific antigen (PSA), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual urine volume (PVR). Results Of the 129 patients, 54 were in the TURP group and 75 were in the ?-blocker group. Statistically significant differences (p<0.05) between the two groups were found in the prostate volume (50.8 ml vs. 34.4 ml), PSA (6.8 ng/ml vs. 3.6 ng/ml), Qmax (6.84 ml/sec vs. 9.99 ml/sec), and IPSS (27.3 vs. 16.8). According to the multiple regression analysis, the significant factors in ?-blocker monotherapy failure were the IPSS (p<0.001) and prostate volume (p=0.015). According to the receiver operating characteristic (ROC) curve-based prediction regarding surgical treatment, the best cutoff value for the prostate volume and IPSS were 35.65 ml (sensitivity 0.722, specificity 0.667) and 23.5 (sensitivity 0.852, specificity 0.840), respectively. Conclusions At the initial diagnosis of BPH, patients with a larger prostate volume and severe IPSS have a higher risk of ?-blocker monotherapy failure. In this case, combined therapy with 5-alpha-reductase inhibitor (5-ARI) or surgical treatment may be useful.
Hong, Kyoung Pyo; Byun, Young Joon; Yoon, Hana; Park, Young Yo
Objective: Our goal was to quantify relationships between adherence to 5-alpha reductase inhibitors (5-ARIs), the risk of acute urinary retention (AUR) and prostate surgery, and medical costs related to patients with benign prostatic hyperplasia (BPH). Methods: Claims recorded over a period of 6.5 years in a nationwide managed care database were analyzed. We conducted time-to-event multivariate analysis to evaluate relationships between adherence (medication possession ratio [MPR] thresholds of 70% or higher, 75% or higher, and 80% or higher), persistence (length of therapy), and the risk of AUR and surgery. We compared mean monthly BPH-related medical costs in patients with MPRs at or above thresholds and those with MPRs below thresholds and determined changes in BPH-related costs associated with 30-day increments of therapy. Results: In AUR analyses (N = 17,293), meeting or exceeding MPR thresholds was associated with a reduced likelihood of AUR for 70% (hazard ratio [HR], 0.380), 75% (HR, 0.613), and 80% (HR, 0.519) (P < 0.05 for all). In prostate surgery analyses (N = 17,739), the likelihood of surgery was reduced with MPR thresholds of 70% or above (HR, 0.294), 75% or above (HR, 0.542), and 80% or above (HR, 0.436) (P < 0.05 for all). A longer duration of therapy was associated with a reduced likelihood of AUR (HR, 0.860) and surgery (HR, 0.884) (P < 0.05 for both). In both populations, adherence and persistence were also associated with significantly decreased BPH-related medical costs. Conclusion: In patients with BPH who received 5-ARI therapy, greater adherence and persistence were associated with significantly reduced risks of AUR and prostate surgery and with significantly lower medical costs. Maximizing adherence may enable patients to realize the potential long-term benefits of 5ARIs.
Gruschkus, Stephen; Poston, Sara; Eaddy, Michael; Chaudhari, Sham
Combination therapy with dutasteride and tamsulosin in men with moderate-to-severe benign prostatic hyperplasia and prostate enlargement: the CombAT (Combination of Avodart® and Tamsulosin) trial rationale and study design
Benign prostatic hyperplasia (BPH) is a highly prevalent condition in aging men, which can be progressive and lead to acute urinary retention (AUR) and the need for surgery. It is commonly treated with ?-blockers and 5?-reductase inhibitors (5ARIs), both of which improve the symptoms of BPH. Long-term treatment with 5ARIs can also reduce the risk of developing AUR and the
Paul Siami; Claus G. Roehrborn; Jack Barkin; Ronaldo Damiao; Marek Wyczolkowski; Annette Duggan; Kim Major-Walker; Betsy B. Morrill
Benign prostatic hyperplasia (BPH) is highly prevalent in older men and causes substantial adverse effects on health. The pathogenesis of this disease is not totally clear. Recent reports have suggested a possible relationship between metabolic syndrome (MetS) and BPH. Single components of MetS (obesity, dyslipidemia, hypertension, and insulin resistance) as well as the syndrome itself may predispose patients to a higher risk of BPH and lower urinary tract symptoms (LUTS). This may stem from changes in insulin resistance, increased autonomic activity, impaired nitrergic innervation, increased Rho kinase activity, pro-inflammatory status, and changes in sex hormones that occur in association with MetS. However, the exact underlying mechanisms that regulate the potential relationship between MetS and BPH/LUTS still need to be clarified. Increased physical activity and dietary strategies may help in decreasing the incidence of MetS and its impact on BPH/LUTS. However, differences in the definitions used to address the examined predictors and endpoints preclude the possibility of arriving at definitive conclusions.
Briganti, Alberto; Suardi, Nazareno; Castiglione, Fabio; Gallina, Andrea; Capitanio, Umberto; Montorsi, Francesco
The aim of this study was to investigate the relationship between prostate specific antigen density and prostate volume with\\u000a microvessel density in patients with benign prostatic hyperplasia and advanced prostatic carcinoma. Sixty-eight patients with\\u000a benign prostatic hyperplasia and 11 patients with advanced prostatic carcinoma participated in the study. The paraffin blocks\\u000a of all patients were stained with CD34 by the
M. Çetinkaya; S. Günçe; E. Ulusoy; F. Aksoy; Ö. Yildiz; Ö. Adsan; C. Özden
Lower urinary tract symptoms (LUTS)-constituting a spectrum disorder that encompasses weak stream, nocturia, and sensations of incomplete emptying and intermittent or hesitant urination-are indicative of lower urinary tract dysfunction (LUTD). LUTD is a progressive disease that can lead to bladder dysfunction if left untreated or treated ineffectively. Sequelae include urinary retention, recurrent UTI, bladder calculi, and, eventually, renal impairment. LUTD involving the prostate is associated with both ageing and inflammation. Tissue inflammation resulting from ageing, infection, or other inflammatory disease processes (for example, type 2 diabetes mellitus) is epidemiologically associated with the subsequent development of tissue fibrosis in multiple organ systems, including the prostate. Recent studies show that tissue fibrosis in the lower urinary tract is associated with LUTD, and suggest that fibrosis might be a previously unrecognized pathobiology that contributes to LUTD. Thus, antifibrotic therapeutic agents should be considered as a new approach to efficaciously treating men with LUTD, especially those who don't experience durable responses to 5?-reductase inhibitors or ?-adrenergic receptor antagonists. PMID:23857178
Rodriguez-Nieves, Jose A; Macoska, Jill A
Benign prostatic hyperplasia (BPH) is an extremely common and chronic condition that can lead to bladder outlet obstruction (BOO) in elderly men. Although pressure-flow studies are considered the most reliable method for evaluating BOO, they are invasive and complicated. Transrectal ultrasonography (TRUS) is a promising alternative because of its minimal invasiveness. Recently, TRUS imaging has been shown capable of measuring the resistive index, a useful parameter for evaluating BOO and for determining proper medical intervention in patients suffering from BPH. PMID:21475953
Shinbo, Hitoshi; Kurita, Yutaka
ObjectivesSince decades plant extracts belong to the most popular drugs for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH)\\/benign prostatic enlargement (BPE). Herein we review biological mechanisms, the placebo effect, results of clinical trials, the role of meta-analyses and guideline recommendations.
Stephan Madersbacher; Anton Ponholzer; Ingrid Berger; Martin Marszalek
Benign prostatic hyperplasia (BPH) is a major health concern for aging men. BPH is associated with urinary voiding dysfunction and lower urinary tract symptoms (LUTS), which negatively affects quality of life. Surgical resection and medical approaches have proven effective for improving urinary flow and relieving LUTS but are not effective for all men and can produce adverse effects that require termination of the therapeutic regimen. Thus, there is a need to explore other therapeutic targets to treat BPH/LUTS. Complicating the treatment of BPH/LUTS is the lack of biomarkers to effectively identify pathobiologies contributing to BPH/LUTS or to gauge successful response to therapy. This review will briefly discuss current knowledge and will highlight new studies that illuminate the pathobiologies contributing to BPH/LUTS, potential new therapeutic strategies for successfully treating BPH/LUTS, and new approaches for better defining these pathobiologies and response to therapeutics through the development of biomarkers and phenotyping strategies. PMID:23913202
Gharaee-Kermani, Mehrnaz; Macoska, Jill A
Should Modest Elevations in Prostate-Specific Antigen, International Prostate Symptom Score, or Their Rates of Increase Over Time be Used as Surrogate Measures of Incident Benign Prostatic Hyperplasia?
Although surrogate measures of benign prostatic hyperplasia (BPH) are often used in epidemiologic studies, their performance characteristics are unknown. Using data from the Prostate Cancer Prevention Trial (n = 5,986), we evaluated prostate-specific antigen (PSA), International Prostate Symptom Score (IPSS), and their rates of change as predictors of incident BPH. BPH (n = 842 cases) was defined as medical or surgical treatment or at least 2 IPSS of 15 or higher. Proportional hazards models were used to measure the associations of baseline PSA, IPSS, and their velocities over 2 years with BPH risk, and time-dependent receiver-operating characteristic curves were used to measure their discriminatory performance. Unit increases in PSA, IPSS, and IPSS velocity were associated with 34%, 35%, and 29% (all P < 0.001) increases in BPH risk, respectively. The areas under the receiver-operating characteristic curves were significantly greater than 0.5 for PSA (0.58, 95% confidence interval (CI): 0.56, 0.60), IPSS (0.77, 95% CI: 0.75, 0.78), and IPSS velocity (0.63, 95% CI: 0.61, 0.65); however there were no cut points at which sensitivity and specificity were both above 75%. We concluded that moderate elevations in PSA, IPSS, or their rates of change should not be used as surrogate measures of incident BPH. PMID:23813705
Schenk, Jeannette M; Hunter-Merrill, Rachel; Zheng, Yingye; Etzioni, Ruth; Gulati, Roman; Tangen, Catherine; Thompson, Ian M; Kristal, Alan R
Objectives. A pooled analysis of all available randomized trials with 2-year follow-up data with finasteride and placebo was undertaken to further investigate recent observations that finasteride use may reduce the occurrence of acute urinary retention (AUR) and benign prostatic hyperplasia (BPH)-related surgical intervention.Methods. Occurrences of AUR and surgical intervention were examined by treatment group in a pooled series of 4222
Jens T. Andersen; J. Curtis Nickel; Villis R. Marshall; Claude C. Schulman; Peter Boyle
The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5g\\/kgbodywt. A positive control
M. Gasco; L. Villegas; S. Yucra; J. Rubio; G. F. Gonzales
This is a controlled efficacy study with doxazosin (4 mg\\/day) in the long-term management of 64 ambulatory patients with benign\\u000a prostatic hyperplasia (BPH). Doxazosin was given for 72 weeks and is being continued. Twenty-three controls were treated with\\u000a prazosin (Minipress-4 mg\\/day) for 24 weeks, after which the results were similar in both the doxazosin (group 1) and prazosin\\u000a (group 2)
S. Dutkiewicz; A. Witeska
This study was conducted to characterise the flavonoid components of total flavan glycoside from Abacopteris penangiana rhizomes (TFA) and its acid hydrolysate (AHT) through HPLC-DAD-ESI-MS/MS analysis, and to investigate the hypothesis that TFA and AHT exhibit anti-benign prostatic hyperplasia (BPH) potential in castrated rats with testosterone-induced BPH. HPLC-MS/MS analysis indicated that TFA is rich in flavan-4-ol glycosides and AHT mainly contains 3-deoxygenated anthocyanidin. After 4 weeks of administration, TFA and AHT successfully decreased the prostate index and prostate specific antigen plasma concentrations in the rats. Histoarchitectural improvement in the prostate gland was also observed. Reduced dihydrotestosterone, VEGF, bFGF, EGF, and KGF levels were observed both in TFA- and AHT-treated rats. Furthermore, the prostatic expression of Blc-2 was inhibited, whereas that of Bax and p53 was activated by TFA and AHT. In conclusion, TFA and AHT have anti-BPH properties. Hence, plants with flavan glycosides have potential use in the treatment of BPH. PMID:23442644
Wei, Han; Wu, Guanghua; Shi, Du; Song, Shanshan; Zhang, Xuenong; Lei, Yongfang; Ruan, Jinlan
Since prostate growth is governed by the androgen signaling pathway, blockade of the pathway is regarded as an appropriate strategy for the treatment of benign prostatic hyperplasia (BPH). Panax ginseng is known to have various pharmacological activities. Of several products of its root, red ginseng, having many bioactive ginsenosides, is most popularly used in Korea, and recently has been reported to control the proliferation of cancer cells. We here tested the effect of a water extract of Korean red ginseng (WKRG) on testosterone-induced prostate hyperplasia. WKRG (daily intraperitoneal injection) prevented prostate overgrowth and epithelial thickening induced by testosterone in rats, and suppressed a rat prostate kallikrein-S3. In human prostate cells, WKRG inhibited testosterone-induced cell proliferation, arrested cell cycle by inducing p21 and p27, and induced apoptosis. Testosterone-induced expression of human kallikrein-3 mRNA and activation of androgen receptor (AR) were effectively inhibited by WKRG. Of the major ginsenosides included in WKRG, 20(S)-Rg3 was identified to repress AR activity and to attenuate prostate cell growth during testosterone stimulation. Moreover, 20(S)-Rg3 downregulated AR by facilitating the degradation of AR protein. WKRG and 20(S)-Rg3 were found to have new pharmacological activities against testosterone-induced prostate overgrowth. Given that red ginseng has been used safely in Asia for 1000 years, red ginseng and 20(S)-Rg3 could be potential therapeutic regimens for treating BPH. PMID:22101440
Bae, Jung-Soo; Park, Hyoung-Sook; Park, Jong-Wan; Li, Shan-Hua; Chun, Yang-Sook
ObjectivesTo examine the rate of prostate cancer detection in three large randomized placebo-controlled benign prostatic hyperplasia trials of dutasteride. Dutasteride, which lowers serum dihydrotestosterone more than 93% by inhibiting type 1 and type 2 5-alpha-reductase, is effective in the treatment of benign prostatic hyperplasia. However, its effect on the development of prostate cancer is unknown.
G. L. Andriole; C. Roehrborn; C. Schulman; K. M. Slawin; M. Somerville; R. S. Rittmaster
The management of benign prostatic hyperplasia (BPH), although based on the best available evidence, should be individualised to patients’ circumstances and personal choices. Subjective symptoms (LUTS), bothersomeness and negative impact on the quality of life are the main reasons for the patient to seek treatment for BPH. Therefore, the improvement of this subjective discomfort ought to be an important treatment
Mark J. Speakman
Introduction/Objective Transurethral resection of the prostate (TURP) is a gold treatment method in older men who develop lower urinary tract symptoms (LUTS) which are caused by benign prostatic hyperplasia (BPH) and benign prostatic obstruction (BPO). The objective of the study was to assess the impact of BPH surgical treatment with TURP method on the quality of life, as a consequence of urinary symptoms. Material and methods The research material was based on 40 patients who, due to BPH, were treated with the method of transurethral resection. International Prostate Symptom Score (IPSS) was used in the research i.e. question Nº 8 that relates to the quality of life, as a consequence of the urinary symptoms. The criteria for the patients to be selected for this type of BPH surgical treatment were good general status of the patient, age under 80, the weight of benign prostatic gland hyperplasia tissue 30–80 grams, postvoid residual urine (PVR) higher than 150 ml, IPSS value >19 points, and Index of Quality of Life (IQL) values > 3 points. All patients, first preoperatively, and then postoperatively, gave answers to IPSS IQL in time intervals of 4, 8 and 12 weeks. Results Difference testing of IQL arithmetic means (AM) between results before the operation, then during the first, second and third checkup was performed with the t-test and Wilcoxon test of equivalent pairs, and has shown that there is a highly statistically significant difference between preoperative values and the values during all the postoperative checkups. Taking into consideration the age subgroups (20 patients between 59 and 69 years and 20 patients between 70 and 80 years), difference testing of arithmetic means between results before the operation and first, second and third checkup, isolated, for each age subgroup, was carried out. It has demonstrated that there is a statistically significant difference between preoperative values and values during all postoperative checkups. Difference testing of arithmetic means between the stated age groups has also been conducted. The t-test and Mann-Whitney test have been used for this purpose and have shown that there is no statistically significant difference between preoperative test results and the results during all postoperative checkups. Conclusion The quality of life, as a consequence of urinary symptoms, has significantly improved after the BPH treatment with TURP method. The impact of TURP on the quality of life is not related to age i.e. TURP is equally efficient regardless of patient’s age.
Despite the fact that almost all men will develop symptoms associated with benign prostatic hyperplasia within their lifetimes, no molecular markers for the disease or its likelihood to progress have been established. A marker of this type could be used to stratify patients into subpopulations as well as to identify individuals whose disease is most likely to progress. Several molecular biomarkers have high potential to fulfill these needs, although none is currently approved for the clinical setting. The future does look promising as research to find novel biologic biomarkers is progressing while existing markers are optimized and validated for clinical use.
Cannon, Grant W.; Getzenberg, Robert H.
Introduction. For decades, transurethral resection of the prostate (TURP) has been the “gold standard” operation for benign prostatic hyperplasia (BPH) but is based mainly on historic data. The historic data lacks use of validated measures and current TURP differs significantly from that performed 30 years ago. Methods. Men who had undergone TURP between 2001 and 2005 were reviewed. International prostate symptom score (IPSS), quality of life (QOL) and peak urinary flow rate (Qmax?), and postvoid residual (PVR) were recorded. Operative details and postoperative complications were documented. Patients were then invited to attend for repeat assessment. Results. 91 patients participated. Mean follow-up time was 70 months. Mean follow-up results were IPSS—7; QoL—1.5; Qmax?—23?mL/s; PVR—45?mL. These were an improvement from baseline of 67%, 63%, 187%, and 80%, respectively. Early complication rates were low, with no blood transfusions, TUR syndrome, or deaths occurring. Urethral stricture rate was higher than anticipated at 14%. Conclusion. This study shows modern TURP still produces durable improvement in voiding symptoms which remains comparable with historic studies. This study, however, found a marked drop in early complications but, conversely, a higher than expected incidence of urethral strictures.
Kallenberg, F.; Hossack, T. A.; Woo, H. H.
Background. 5?-Reductase inhibitors (5ARIs) are commonly used to treat benign prostate hyperplasia (BPH) by blocking the conversion of testosterone into the more potent dihydrotestosterone. This study explored a possible association between the use of the 5ARIs finasteride and dutasteride and the subsequent risk of prostate cancer or other cancers. Methods. We analyzed data from the Taiwanese National Health Insurance system. In a BPH cohort, we identified 1,489 patients with cancer and included them in our study group. For the control group, 3 patients without cancer were frequency matched with each BPH case for age, BPH diagnosis year, index year, and month. Information regarding past 5ARI use was obtained from the Taiwanese National Health Insurance Research Database (NHIRD). Multivariate logistic regression analysis was conducted, and odds ratio (OR) and 95% confidence interval (CI) were estimated. Results. Finasteride use marginally increased the incidence of prostate and overall cancer at a level of statistical significance (prostate cancer: OR = 1.90; 95% CI: 1.00–3.59; overall cancer: OR = 1.51; 95% CI: 1.00–2.28). Dutasteride use significantly increased kidney cancer risk (OR = 9.68, 95% CI: 1.17–80.0). Dosage analysis showed that lower doses of finasteride were associated with higher overall and prostate cancer risks. The major limitation is the lack of important data in the NHIRD, such as prostate cancer histologic grades, smoking habits, alcohol consumption, body mass index, socioeconomic status, and family history of cancer. Conclusions. This population-based nested case-control study suggested that finasteride use may increase prostate and overall cancer risks for patients with BPH. The effects were more prominent for patients using lower doses of finasteride.
Liang, Ji-An; Sun, Li-Min; Lin, Ming-Chia; Chang, Shih-Ni; Sung, Fung-Chang; Muo, Chih-Hsin
Objectives. To study the variability of assessment instruments (symptom questionnaires and flow rate recordings) in healthy volunteers during repeat administration in short intervals. To study the effect of inclusion criteria-based censoring of patients during screening for benign prostatic hyperplasia (BPH) treatment trials on the outcome of subsequent tests.Methods. One hundred forty-five male volunteers without known prostatic diseases with a mean
Scott M. Sech; Juan D. Montoya; Pablo A. Bernier; Emma Barnboym; Sherril Brown; Allison Gregory; Claus G. Roehrborn
Benign prostatic hyperplasia (BPH) is a common disease of aging men. Current medical treatment for this condition is only partially effective, therefore many patients must undergo surgery for symp- tomatic relief. BPH is caused by an increase in prostate epithelial and stromal cells, especially the latter. Since BPH stromal cells have a long life span and are not very responsive
S. J. PADAYATTY; M. MARCELLI; T. C. SHAO; G. R. CUNNINGHAM
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. PMID:9506725
Colao, A; Marzullo, P; Ferone, D; Spiezia, S; Cerbone, G; Marinò, V; Di Sarno, A; Merola, B; Lombardi, G
The bioactive form of vitamin D, 1?, 25-dihydroxyvitamin D3 (1?, 25(OH)2D3), is a secosteroid hormone that binds to the vitamin D receptor (VDR), a member of the nuclear receptor super-family expressed in many cell types, and modulates a variety of biological functions. 1?, 25(OH)2D3 is essential for bone and mineral homeostasis, but also regulates growth and differentiation of multiple cell types, and displays immunoregulatory and anti-inflammatory activities. The antiproliferative, prodifferentiative, antibacterial, immunomodulatory and anti-inflammatory properties of synthetic VDR agonists could be exploited to treat a variety of chronic inflammatory and autoimmune diseases, including benign prostatic hyperplasia (BPH). It has been hypothesized that VDR may influence both the risk of a variety of diseases and their occurrence and prognosis. However, earlier studies investigating the associations between specific VDR polymorphisms and various diseases often show controversial results. We performed a systematic review of the current literature on vitamin D and BPH using the PubMed and Web of Knowledge databases. The aim of this review is to summarize the current knowledge on the utility of the VDR gene regarding prostate growth as well as the pathogenesis and treatment of BPH, a complex syndrome characterized by a static component related to prostate overgrowth, a dynamic component responsible for urinary storage symptoms, and an inflammatory component. Despite the massive advances in recent decades, further research is needed to fully characterize the exact underlying mechanisms of VDR action on BPH and to comprehend how these cellular changes translate into clinical development in physical concert. PMID:23450267
Manchanda, Parmeet Kaur; Kibler, Aaron J; Zhang, Mei; Ravi, Janani; Bid, Hemant K
Purpose The purpose of this study was to evaluate the annual changes in prostate variables and style of surgical treatment of patients with benign prostatic hyperplasia (BPH) over the past 12 years. Materials and Methods The subjects were 918 patients (January 1999-November 2010) who were treated by either open prostatectomy or transurethral resection of prostate (TURP). Every year, the performance ratio between open prostatectomy and TURP was evaluated. Before surgery, total and transitional zone volumes of the prostate were measured by transrectal ultrasonography (TRUS). After surgery, resection weight and residual volume of the prostate were measured by TRUS. Results From 2001 through 2010, the performance ratio of TURP increased greatly from 89% to 97%. During 1999 to 2010, the total volume of the prostate increased from 40.0 cc to 55.0 cc in the TURP group and from 74.1 cc to 116.7 cc in the open prostatectomy group. During 1999 to 2010, the mean resection volume of the TURP group increased from 2.3 cc to 20.1 cc. Also, the mean resection volume of the open prostatectomy group increased from 59.3 cc to 114.3 cc. During 1999 to 2003, the resection time of the TURP group decreased from 72.9 minutes to 43.2 minutes. Conclusions During 1999 through 2010, the performance ratio between open prostatectomy vs TURP was high for TURP. The total volume and resection volume of the prostate increased annually, and the resection time decreased annually.
Shin, Yu Seob
The present study was conducted to evaluate the effect of a fraction of macroporous resin (FMR), a bioactive component of Smilax china L., on benign prostatic hyperplasia (BPH) in castrated rats induced by testosterone propionate. Rats were randomly divided into five groups: the negative control group (sham-operated), the model group, two FMR-treated groups (at doses of 300 mg/kg and 600 mg/kg of body weight), and the positive control group (treated with finasteride at the dose of 3 mg/kg). Drugs were administered once a day for three consecutive weeks by gastric gavage. Prostates were weighed, testosterone and dihydrotestosterone (DHT) levels in serum were determined, and histopathological examinations were carried out. FMR treatment inhibited prostatic hyperplasia, reducing the DHT level in serum and improving the prostate gland morphology compared with the model group. The overall results of this study suggest that FMR is effective at inhibiting experimentally induced prostate enlargement, and it presents a valuable resource for the treatment of human BPH. PMID:22510101
Chen, Jing; Xiong, Chao-Mei; Song, Shan-Shan; Han, Pan; Ruan, Jin-Lan
Abstract The present study was conducted to evaluate the effect of a fraction of macroporous resin (FMR), a bioactive component of Smilax china L., on benign prostatic hyperplasia (BPH) in castrated rats induced by testosterone propionate. Rats were randomly divided into five groups: the negative control group (sham-operated), the model group, two FMR-treated groups (at doses of 300?mg/kg and 600?mg/kg of body weight), and the positive control group (treated with finasteride at the dose of 3?mg/kg). Drugs were administered once a day for three consecutive weeks by gastric gavage. Prostates were weighed, testosterone and dihydrotestosterone (DHT) levels in serum were determined, and histopathological examinations were carried out. FMR treatment inhibited prostatic hyperplasia, reducing the DHT level in serum and improving the prostate gland morphology compared with the model group. The overall results of this study suggest that FMR is effective at inhibiting experimentally induced prostate enlargement, and it presents a valuable resource for the treatment of human BPH.
Chen, Jing; Xiong, Chao-Mei; Song, Shan-Shan; Han, Pan
Purpose Transurethral resection of the prostate (TURP) is still considered the gold standard in the treatment of benign prostatic hyperplasia (BPH). However, open prostatectomy is indicated for prostate glands over 75 ml. There have been few reports concerning the use of TURP for large prostate glands over 100 ml. Herein we compared the effectiveness of monopolar TURP, bipolar TURP, and open prostatectomy in prostate glands larger than 100 ml. Materials and Methods We reviewed the data of 48 patients with prostate glands larger than 100 ml. A total of 19, 17, and 12 patients underwent monopolar TURP (group A), bipolar TURP (group B), or open prostatectomy (group C), respectively. Preoperative International Prostate Symptom Score (IPSS), maximal flow rate (Qmax), prostate volume, resected tissue volume, resection velocity, and operative time were documented. Postoperative hemoglobin, serum sodium change, hospital stay, and postoperative 6-month IPSS and Qmax were evaluated. Results The prostate volumes did not differ significantly among the three groups. Operative time was similar in the two TURP groups, but open prostatectomy required a longer operative time. There was no significant difference in the resected prostate tissue or resection velocity between the two TURP groups. There was a marked decrease in postoperative serum sodium in the monopolar group compared with the other two groups. Among the groups, bipolar TURP required a shorter hospitalization. Postoperative IPSS, quality of life (QoL), and Qmax improved significantly in all groups. Conclusions Even for large prostate glands, the results of this study suggest that bipolar TURP is an effective and safe operation owing to the significant improvements in voiding symptoms, shorter hospitalization, and fewer complications such as transurethral resection syndrome.
Kwon, Joon Seok; Lee, Jung Woo; Lee, Seung Wook; Choi, Hong Yong
Interstitial laser-induced coagulation (ILC) is a new, minimally invasive, procedure for the treatment of benign prostatic hyperplasia (BPH). It is based on the placement of special light guides in the prostatic tissue, either transurethrally or perineally. The radiation source is a Nd-YAG laser, which is active for 3 or 5 min per fiber placement, respectively, with the power reduced stepwise. The coagulation necroses caused shrink during follow-up, leading to a decrease in the obstruction. In 239 patients treated in this way the mean I-PSS-Score fell from 25.4 to 8.1 points and the quality of life index from 4.1 to 1.6, the urinary peak flow rate increased from 7.7 to 16.3 ml/s, the residual urine volume fell from 151 to 32 ml, and the mean prostate volume declined from 47.4 to 32.2 ml in the first 3 months of follow up; 9.2% of the patients required further treatment within 1 year because of persistent obstruction. The complication rate was low. Statistical analysis showed no factors allowing prediction of the outcome. ILC is an effective method with few side effects and complications, and it has a wide range of indications for all BPH patients. PMID:7538715
Muschter, R; Zellner, M; Hessel, S; Hofstetter, A
This study was carried out to obtain information on the efficacy and safety of the controlled release formulation of the doxazosin Gastrointestinal Therapeutic System (GITS) in Taiwanese subjects with benign prostatic hyperplasia (BPH). Studies of doxazosin in Asian populations for this indication have lacked data particularly from Taiwan. This was an 8-week, post-marketing, open-label, non-comparative study. Eighty male subjects (mean age=64 years) with BPH received doxazosin GITS 4 mg once daily. At week 4, subjects who achieved an increase in maximum urinary flow rate (Qmax) of ?3mL/s and a ?30% reduction in the total International Prostate Symptom Score (IPSS) continued on doxazosin GITS 4 mg for the remaining 4 weeks; all other subjects were up-titrated to 8 mg once daily. Change from baseline at weeks 4 and 8 (primary endpoint) in IPSS and Qmax was evaluated using two-sided paired t tests for the intent-to-treat population. Safety was assessed throughout the study. A total of 53 (66.3%) subjects completed the study. Baseline Qmax and IPSS were 10.7+3.4 mL/s and 20.6+5.4, respectively. At week 8, a significant increase from baseline in Qmax of 3.3+4.6 mL/s (95% confidence interval = 2.2-4.4, p< 0.001) and a significant decrease in total IPSS of -8.9 + 7.0 (95% confidence interval=-10.5 to -7.3, p< 0.001) was observed. The most common treatment-related adverse event was dizziness. Doxazosin GITS 4 mg per day (with an 8-mg titration step) effectively improved symptoms of BPH. The results from this study provide further information for clinicians on the use of doxazosin GITS for the treatment of BPH, particularly in Taiwanese patients. PMID:20950778
Sun, Guang-Huan; Tsui, Ke-Hung; Wu, Tony T; Chang, Chao-Hsiang; Cheng, Chen-Li; Schou, Manjula
The use of botanicals and supplements have markedly increased in men that are seeking increased protection against the potential onset and symptomatic relief of lower urinary tract symptoms that are commonly experienced with benign prostatic hyperplasia (BPH). While this implies a positive trend and considers that men are taking a more active role in health and prevention, dialog between the
Jillian L. Capodice; Aaron E. Katz
Predicting the clinical outcome prior to minimally invasive treatments for Benign Prostatic Hperlasia (BPH) cases would be very useful. However, clinical prediction has not been reliable in spite of multiple assessment parameters such as symptom indices and flow rates. In this study, Artificial Intelligence (AI) algorithms are used to train computers to predict the surgical outcome in BPH patients treated by TURP or VLAP. Our aim is to investigate whether AI can reproduce the clinical outcome of known cases and assist the urologist in predicting surgical outcomes. Four different AI algorithms are used.
Megherbi, Dalila B.; Boulenouar, A. J.; Kaula, N.; Tracy, D.; Lodhi, S. M.; Dixon, C.
We examined the effectiveness of supplemental administration of flavoxate hydrochloride in patients with benign prostatic hyperplasia (BPH) whose nocturia was not adequately relieved by an alpha1-adrenoceptor blocker. Fifty-two patients who had two or more nocturnal micturition after administration of tamsulosin hydrochloride or naftopidil for 4 weeks or more received 400-600 mg of flavoxate hydrochloride in addition to an alpha1-adrenoceptor blocker for another 8-12 weeks. With supplemental administration of flavoxate hydrochloride, significant improvement was observed in the number of nocturnal micturition, total International Prostate Sympton Score, quality of life score and BPH impact index. No significant change was observed in the voided volume, Qmax, voiding time and residual urine volume. Supplemental administration of flavoxate hydrochloride is therefore effective for the improvement of nocturia and QOL in BPH patients resistant to an alpha1-adrenoceptor blocker. PMID:18411771
Kato, Shinobu; Kusaka, Mamoru; Shiroki, Ryoichi; Izumitani, Masanobu; Asano, Haruyoshi; Ooki, Takahiro; Yanaoka, Masanori; Hoshinaga, Kiyotaka
Benign prostatic hyperplasia (BPH) results from an increase in both epithelial and stromal compartments of the human prostate. Although inhibitors of 5alpha-reductase such as finasteride have been shown to reduce the size of BPH tissues by inducing apoptosis, their mechanisms of action still remain unknown. The present study supports that such a process triggered by finasteride is caspase dependent with a possible involvement of two effector caspases (caspase-3 and 6) and two initiator caspases (caspase-8 and 9). Indeed, by using tissues from patients affected by BPH and treated by finasteride (5 mg/d) for 2-3, 6-8, or 27-32 d, we observed that the 5alpha-reductase inhibitor induced apoptosis in epithelial cells (evaluated through cell number positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) as early as 2-3 d of treatment, with a maximal activity (250-fold increase, P < 0.0001) at 6-8 d of treatment. However, after 27-32 d of treatment, the number of apoptotic cells was reduced and was close to control. Caspases-3, -6, -8, and -9 were immunolocalized to (basal and secretory) epithelial cells and to a lesser extent to stromal cells. Activated caspase-3 immunoexpression was restricted to epithelial secretory cells, and its immunostaining intensity appeared to be higher in BPH tissues from patients treated for 2-3 or 6-8 d. Consistently, in Western blotting analyses, activated caspases-3 and -6 were detected as early as 2-3 d of treatment in BPH tissues, and their levels were increased after 6-8 d of treatment. In real time quantitative PCR experiments, caspase-3 and -6 mRNA levels were found to be unchanged after finasteride treatment. Activated caspase-8 was not detected in the different conditions tested, whereas activated caspase-9 protein levels were maximally enhanced after 2-3 d of finasteride treatment. In conclusion, we report here that finasteride treatment of BPH tissues induced a caspase-dependent apoptotic process restricted to epithelial cells by activating effector caspases-3 and -6 and exhibited a transient action because the apoptotic process was no longer observed after 27-32 d of treatment. PMID:15507514
Bozec, Aline; Ruffion, Alain; Decaussin, Myriam; Andre, Jean; Devonec, Marian; Benahmed, Mohamed; Mauduit, Claire
Objectives:? Various types of minimally invasive surgical treatments, including transurethral resection of prostate (TURP), are being carried out in Japan for patients with benign prostatic hyperplasia (BPH). The aim of the present study was to elucidate the current status of perioperative care for these treatments by carrying out a nationwide survey. Methods:? Assisted by the Japanese Endourology and ESWL Association, perioperative data from 157 institutions participating in this survey were collected and analyzed. Results:? This survey included 3918 patients undergoing TURP, 242 TUR in saline (TURis), 638 holmium laser enucleation of the prostate (HoLEP), 90 holmium laser ablation (HoLAP) and 241 photoselective vaporization (PVP). Mean operative time was shorter in TURP (71?min) and longer in HoLEP (127). Although no transfusions were required in cases undergoing HoLAP or PVP, blood was frequently transfused in those undergoing TURis (25.6%), TURP (10.2%) and HoLEP (7.8%), and the difference was significant. During the hospital stay, the incidence of TUR-syndrome, postoperative bleeding requiring bladder irrigation, acute urinary retention/difficulty on micturition and pad use at discharge was highest in TURP (2.3%), TURis (7.9%), HoLAP (16.7%) and HoLEP (15.1%), respectively. Two patients undergoing TURP died (0.05%). The shortest mean postoperative hospital stay was for PVP (1.6?days, even if the readmission rate within 90?days was the highest in this same group; 6.2%). Perioperative care during hospital stay varied among the five types of procedures. Conclusions:? This survey provides useful documentation on the current status of minimally invasive treatments for BPH in Japan. Complication rates for TURP are not significantly higher as compared with other procedures. Thus, TURP can still be considered as the gold standard for BPH treatment. PMID:21276084
Okamura, Kikuo; Nojiri, Yoshikatsu; Seki, Narihito; Arai, Yoichi; Matsuda, Tadashi; Hattori, Ryohei; Hasegawa, Tomonori; Naito, Seiji
Benign prostatic hyperplasia is a nonmalignant adenomatous enlargement of the periurethral prostate gland. It is a common disease in older men. In addition to man, spontaneous benign prostatic hyperplasia occurs in chimpanzee and the dog. Alternatives to these spontaneous models are induced benign prostatic hyperplasia, xenografts and in vitro models. Xenografts may be induced by cells cultured in vitro or by the heterotransplantation of primary surgical specimens into immunosuppressed mice. The purpose of this review is to integrate data from more than 30 years of heterotransplantation research in the study of benign hyperplasia of the prostate. Heterotransplantation has provided data regarding the histopathology, morphology, tissue markers, androgen receptor expression, tissue kinetics, take rate and tissue vasculature for this prostate disease. There are advantages, as well as limitations, that have been identified for human prostate disease heterotransplants versus xenotransplantation of cultured cells. Overall, heterotransplanted tissue is better at retaining tissue morphology, pathology, secretory activity, expression of tissue markers and human vasculature of the patient's original specimen. Furthermore, heterotransplanted tissue preserves the three-dimensional tissular architecture of the prostate to maintain critical stromal–epithelial cell interactions.
We assessed the therapeutic efficacy and safety of laser prostatectomy (LP) for treating benign prostatic hyperplasia (BPH) in patients on oral anticoagulation. We systematically reviewed previous reports, using the Pubmed database and bibliographies of retrieved articles and reviews. The oral anticoagulation included coumarin derivatives and platelet-aggregation inhibitors (PAI). Previous studies do not allow the establishment of definitive conclusions for managing patients on oral anticoagulation and who require BPH surgery. No randomized studies are available. Nevertheless, compared to transurethral resection of the prostate (TURP), LP seems to decrease the risk of haemorrhage in patients taking PAI or coumarin derivatives. Therefore, LP is a useful alternative to TURP for managing patients on oral anticoagulation, and could be proposed as the first intention for those patients. Continuing PAI during the procedure is feasible. A replacement of coumarin derivatives by low molecular weight heparin is preferable. No conclusion can be reached on the preferred type of laser technique to treat these patients, but data on laser enucleation is much less abundant and conclusive than that on laser vaporization. PMID:19154457
Descazeaud, Aurélien; Robert, Gregoire; Azzousi, Abdel Rahmene; Ballereau, Charles; Lukacs, Bertrand; Haillot, Olivier; Dumonceau, Olivier; Devonec, Marian; Fourmarier, Marc; Saussine, Christian; de la Taille, Alexandre
Relief of benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms by ?-blockers (??-adrenoceptor antagonists) is mediated primarily through the blockade of ?(1A)-receptors, leading to relaxation of smooth muscle in the prostate and bladder neck. Early ?-blockers that were nonselective for adrenoceptor subtypes have been associated with blood pressure-related adverse effects, such as orthostatic hypotension, that may be attributed at least in part to the blockade of ?(1B)-adrenoceptors in arterial vessels. Silodosin, a novel ?-blocker with exceptionally high selectivity for ?(1A-) versus ?(1B)-adrenoceptors, was recently approved in the United States for the treatment of urinary symptoms related to BPH. The unique receptor selectivity profile likely accounts for some of the desirable clinical features of the drug. Silodosin possesses an excellent cardiac- and blood pressure-related safety profile, and data have demonstrated that it does not promote QT-interval prolongation. Therapeutic doses of silodosin are safe for men with mild-to-moderate liver dysfunction; dosage adjustment is recommended in those with moderate renal impairment. The drug should not be taken with potent cytochrome P450 3A4 inhibitors. Silodosin may be especially beneficial in patients who need to maximize cardiovascular tolerability. PMID:21114397
Lepor, Herbert; Hill, Lawrence A
Silodosin is an ?-adrenoceptor antagonist with high selectivity for ?(1A)- relative to ?(1B)- adrenoceptors. In men aged >50 years with benign prostatic hyperplasia (BPH), silodosin 8 mg once daily, compared with placebo, was associated with a significantly more rapid and effective improvement in the total International Prostate Symptom Score (IPSS) and the storage and voiding IPSS subscores in three 12-week, phase III trials conducted in Europe and the US. In the European trial, silodosin was at least as effective as tamsulosin 0.4 mg once daily in improving the total IPSS. Silodosin was significantly more effective than placebo (all three phase III trials) and tamsulosin (European phase III trial) in simultaneously improving nocturia, frequency and incomplete emptying, according to a post hoc analysis. Long-term, open-label extension trials demonstrated that silodosin provided sustained relief of the signs and symptoms of BPH for up to 1 year. Silodosin was generally well tolerated, and was associated with minimal cardiovascular adverse effects. Abnormal ejaculation, a class effect of ?(1A)-adrenoceptor antagonists, was the most common silodosin-associated adverse reaction, but resulted in treatment withdrawal of only a limited number of patients. PMID:21568366
Curran, Monique P
A total of 248 hypertensive patients 45 years old or older with benign prostatic hyperplasia (BPH) was included in this 16-week, multicenter, double-blind, placebo-controlled, parallel-group dose-response study. Doxazosin, a selective alpha 1-adrenoceptor antagonist, produced a significant increase in maximum urinary flow rate (2.3 to 3.6 ml. per second) at doses of 4 mg., 8 mg. and 12 mg., and in
Jay Y. Gillenwater; Richard L. Conn; Steven G. Chrysant; Johnny Roy; Michael Gaffney; Kathleen Ice; Norma Dias
This study examined efficacy and safety of the 980 nm side-firing diode laser operating at a power of 100 W in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). Patients were selected for surgery on the basis of maximum urinary flow rate (Qmax) ?15 ml\\/s or transvesically measured post-voiding residual volume (PVR) >100 ml in conjunction
Objectives:Dutasteride, a dual inhibitor of Type 1 and Type 2 5?-reductase, has been shown to improve disease measures in patients with symptomatic benign prostatic hyperplasia (BPH) in three randomised, placebo-controlled, large-scale, 2-year Phase III clinical studies. This paper reports the pooled results of a 2-year open-label extension of the three randomised studies assessing the long-term efficacy and safety of dutasteride.
Frans Debruyne; Jack Barkin; Peter van Erps; Mario Reis; Teuvo L. J. Tammela; Claus Roehrborn
Chinese herbal medicine is commonly used as a treatment for benign prostatic hyperplasia (BPH), but its efficacy and safety remain to be examined. To compare the efficacy and adverse events of Chinese herbal medicine alone or used adjuvantly with Western medications for BPH. Two independent reviewers searched the major electronic databases for randomized controlled trials comparing Chinese herbal medicine, either in single or adjuvant use with Western medication, with placebo or Western medication. Relevant journals and grey literature were also hand-searched. The outcome measures included changes in urological symptoms, urodynamic measures, prostate volume and adverse events. The frequency of commonly used herbs was also identified. Out of 13 922 identified citations of publications, 31 studies were included. Eleven studies with a Jadad score ?3 were selected for meta-analysis. Chinese herbal medicine was superior to Western medication in improving quality of life and reducing prostate volume. The frequency of adverse events in Chinese herbal medicine was similar to that of placebo and less than that of Western medication. The evidence is too weak to support the efficacy of Chinese herbal medicine for BPH due to the poor methodological quality and small number of trials included. The commonly used herbs identified here should provide insights for future clinical practice and research. Larger randomized controlled trials of better quality are needed to truly evaluate the efficacy of Chinese herbal medicine.
Ma, Chun Ho; Lin, Wai Ling; Lui, Sing Leung; Cai, Xun-Yuan; Wong, Vivian Taam; Ziea, Eric; Zhang, Zhang-Jin
Exigencies of societal demands for alternatives to the not inconsiderable morbidity and significant and increasing cost of\\u000a transurethral resection of the prostate (TURP) paved the way for development of a multitude of therapies for obstructive benign\\u000a prostatic hyperplasia (BPH). Among them, laser prostatectomy (LP) attracted much attention. However, phenomenal appeal of\\u000a earlier coagulative and later cutting (enucleative) or even some
Reza S. Malek
Abstract Purpose: We compared the safety and efficacy of diode laser enucleation of the prostate (DiLEP) with plasmakinetic enucleation and resection of the prostate (PKERP). Patients and Methods: A total of 80 patients with bladder outflow obstruction from benign prostatic hyperplasia (BPH) were randomly assigned to either DiLEP or PKERP prospectively. All patients were assessed preoperatively and followed up at 3, 6, and 12 months postoperatively. Baseline characteristics of the patients, perioperative data, and postoperative outcomes were compared. The operative data and perioperative and postoperative complications were also recorded. Results: The preoperative data were comparable between the two groups. The DiLEP group had significantly shorter operative time, postoperative irrigation, time and catheterization time than the PKERP group (P=0.000, P=0.000 and P=0.000). The drop in hemoglobin level was statistically significantly less in the DiLEP group (P=0.002). There were no statistical differences in complications between the two groups except irritative symptoms (P=0.018). At the 3, 6, and 12-month follow-up, no statistically significant differences were observed between the two groups in International Prostate Symptom Score, maximum flow rate, quality of life, postvoid residual, prostate volume, and prostate-specific antigen level (P>0.05). Conclusions: The efficacy of DiLEP and PKERP were similar for relieving obstruction and low urinary tract symptoms. DiLEP provides less risk of hemorrhage, reduced bladder irrigation, and catheter times. The downward morcellation technique is more efficient than the resection technique. Future well designed randomized trials with extended follow-up and larger sample sizes may be needed to better verify the advantage of DiLEP in treating patients with symptomatic BPH. PMID:23879477
Xu, Abai; Zou, Yong; Li, Bingkun; Liu, Chunxiao; Zheng, Shaobo; Li, Hulin; Xu, Yawen; Chen, Binshen; Xu, Kai; Shen, Haiyan
Introduction: In the present study, we evaluated the effect of transurethral resection of the prostate (TUR-P) on prostatic resistive index (RI) in patients with benign prostatic hyperplasia(BPH). Patients and Methods: Forty BPH patients who were candidates for prostatectomy were prospectively included in the study. Prostatic RI was measured using power Doppler imaging (PDI) before TUR-P. In the postoperative follow-up, all
Cuneyt Ozden; Isa Gunay; Tagmac Deren; Suleyman Bulut; Ozdem Levent Ozdal; Suha Koparal; Ali Memis
Factors Affecting the Improvement of the Initial Peak Urinary Flow Rate after Transurethral Resection of the Prostate or Photoselective Vaporization of the Prostate for Treating Benign Prostatic Hyperplasia
Purpose We evaluated the factors that affect the improvement of the initial peak flow rate after transurethral resection of the prostate (TURP) or photoselective vaporization of the prostate (PVP) for benign prostatic hyperplasia (BPH) patients by using noninvasive tools. Methods One hundred and twenty seven BPH patients who had undergone TURP or PVP between January 2005 and May 2009 were evaluated. They were divided into 2 groups: the postoperative initial peak urinary flow rate (Qmax) was less than 10 mL/sec (Group 1; n=37, TURP=11, PVP=26) and more than 10 mL/sec (Group 2; n=90, TURP=41, PVP=49). We confirmed the patients' preoperative check lists. The check list were the international prostate symptom score (IPSS), the quality of life score, a past history of acute urinary retention (AUR), body mass index and/or pyuria, the serum prostate-specific antigen (PSA) level and the prostate volume, the prostate transitional zone volume and prostatic calcification. The initial Qmax was measured at the outpatient clinic one week after discharge. Results The improvement rate was not significant difference between the TURP group (78.8%) and the PVP group (65.3%). The efficacy parameters were the IPSS-storage symptom score, the prostate volume, the PSA level and a past history of AUR. The IPSS-storage symptom scores of Group 1 (12.3±3.3) was higher than those of Group 2 (10.5±1.7). The prostate volume of Group 2 (42.3±16.6 g) was bigger than that of Group 1 (36.6±7.8 g). The PSA level of Group 2 (3.8±2.6 ng/mL) was higher than that of Group 1 (2.6±2.6 ng/mL). A past history of AUR in Group 1 (35.1%) was more prevalent than that of Group 2 (15.6%). Conclusions The non-invasive factors affecting the initial Qmax after TURP or PVP were the IPSS-storage symptom score, the prostate volume and a past history of AUR. Accordingly, in patients who have a higher IPSS-storage symptom score, a smaller prostate volume and a history of AUR, there might be a detrimental effect on the initial Qmax after TURP or PVP. These factors might also be used as long-term prognostic factors.
Choi, Hwa Sub; Kim, Dong Jun; Kim, Dong Suk; Jeon, Kyoung Pil
Introduction: Clinically benign prostatic hyperplasia (BPH) is classically associated by the progressive development of lower urinary tract symptoms (LUTS). The incidence of bothersome LUTS is associated with age and may vary in patients over 50 years old. In many developing countries with an aging population, BPH associated with LUTS has become a major health issue. To optimize quality of care and control of cost, there is an imperative need to examine the pattern of BPH management. The goal of this study is to capture the Canadian trend in surgical management of BPH and the use of laser therapy during the last 5 years from 2007–2008 to 2011–2012. Methods: We collected the number of transurethral resection of the prostate (TURP) procedures performed in each province in Canada from the Canadian Institute for Health Information (CIHI) reports for the fiscal years (April 1st–March 31st) of 2007–2008, 2008–2009, 2009–2010, 2010–2011 and 2011–2012. Results: Overall, the total number of TURP procedures remained stable from 20 294 procedures per year in 2007 to 20 629 in 2011. In terms of distribution according to provinces, in 2011, about 40% of procedures were performed in Ontario, 20% in BC, 18 in Quebec and 8% in Alberta. These proportions between provinces have remained similar and stable between 2007 and 2011. In contrast, the number of alternative minimally invasive procedures has slowly grown from 767 interventions in 2007 to 1559 in 2011. Overall, laser procedures represented 7.6% of the total number of BPH surgeries in Canada in 2011. The contribution of laser therapy to the amount of total BPH procedures largely varied between provinces. Conclusions: The use of minimally invasive laser procedure alternatives to TURP is progressively growing. Among the novel laser therapies, HoLEP and GreenLight vaporization are the only procedures that have demonstrated equivalent outcomes compared to TURP in randomized clinical trials. Furthermore, due to shorter hospital stay, these novel laser modalities have the potential to reduce healthcare expenses for the treatment of BPH. We can infer that following the trend observed in the United States, the number of laser therapies for BPH in Canada may increase significantly during the coming years.
Hueber, Pierre-Alain; Zorn, Kevin C.
TURP for many years has been considered the gold standard for surgical treatment of BPH. Symptoms relief, improvement in Maximum flow rate and reduction of post void residual urine have been reported in several experiences. Notwithstanding a satisfactory efficacy, concerns have been reported in terms of safety outcomes:intracapsular perforation, TUR syndrome, bleeding with a higher risk of transfusion particularly in larger prostates have been extensivelyreported in the literature.IN THE RECENT YEARS THE USE OF NEW FORMS OF ENERGY AND DEVICES SUCHAS BIPOLAR RESECTOR, HO: YAG and potassium-titanyl-phosphate laserare challenging the role of traditional TURP for BPH surgical treatment.In 1999 TURP represented the 81% of surgical treatment for BPHversus 39% of 2005. Is this a marketing driven change or is there areal advantage in new technologies?We analyzed guidelines and higher evidence studies to evaluate therole of the most relevant new surgical approaches compared to TURPfor the treatment of BPH.In case of prostates of very large size the challenge is ongoing, withminimally invasive laparoscopic approach and most recently roboticapproach. We will evaluate the most recent literature on thisemerging field. PMID:22164196
Rocco, Bernardo; Albo, Giancarlo; Ferreira, Rafael Coelho; Spinelli, Matteo; Cozzi, Gabriele; Dell'orto, Paolo; Patel, Vipul; Rocco, Francesco
Throughout the past decade, numerous techniques for the treatment of benign prostatic hyperplasia have emerged. Laser therapy,\\u000a in particular, has gained widespread popularity among urologists. Since its inception in 1996, holmium laser enucleation of\\u000a the prostate (HoLEP) has been evaluated rigorously in the treatment of glands of all sizes. HoLEP has produced superior relief\\u000a of bladder outlet obstruction as compared
Jessica Mandeville; Ehud Gnessin; James E. Lingeman
Purpose Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. Materials and Methods We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. Results A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Conclusions Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5?-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older, hypogonadal men with symptomatic benign prostatic hyperplasia.
Page, Stephanie T.; Hirano, Lianne; Gilchriest, Janet; Dighe, Manjiri; Amory, John K.; Marck, Brett T.; Matsumoto, Alvin M.
The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required. PMID:17289361
Gasco, M; Villegas, L; Yucra, S; Rubio, J; Gonzales, G F
The safety and effectiveness of tissue ablation by coagulative necrosis with high-intensity focused ultrasound (HIFU) applied through a rectal probe to 36 patients with symptomatic benign prostatic hyperplasia (BPH) was investigated in a phase II clinical trial. Overall, HIFU treatment was well tolerated, the mean hospital stay being 1.1 days. Negative side effects were transient urinary retention in 32/36 patients, hematuria in 2 patients and hematospermia resolving after 3-4 weeks (n = 15). After 3 months the maximum flow rate/s (Qmax) increased from 9.0 +/- 3.9 to 14.4 +/- 7.0 ml/s, the median flow rate/s (QM90) from 4.9 +/- 2.4 to 7.6 +/- 4.17 ml/s; the postvoid residual volume decreased from 128 +/- 88 to 57 +/- 35 ml and the AUA symptom score from 25.5 +/- 5 to 13.2 +/- 4.4. In conclusion, it was shown that tissue ablation in patients with symptomatic BPH using HIFU is safe and dramatically reduces both obstructive and irritative symptoms and leads to a significant increase in uroflow and a decrease in postvoid residual volume. PMID:7685695
Madersbacher, S; Kratzik, C; Szabo, N; Susani, M; Vingers, L; Marberger, M
Naftopidil, approved only in Japan, is an ?1-adrenergic receptor antagonist (?1-blocker) used to treat lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Different from tamsulosin hydrochloride and silodosin, in that it has higher and extremely higher affinity respectively, for the ?1A-adrenergic receptor subtype than for the ?1D type, naftopidil has distinct characteristics because it has a three times greater affinity for the ?1D-adrenergic receptor subtype than for the ?1A subtype. Although well-designed large-scale randomized controlled studies are lacking and the optimal dosage of naftopidil is not always completely determined, previous reports from Japan have shown that naftopidil has superior efficacy to a placebo and comparable efficacy to other ?1-blockers such as tamsulosin. On the other hand, the incidences of ejaculatory disorders and intraoperative floppy iris syndrome induced by naftopidil may be lower than for tamsulosin and silodosin having high affinity for the ?1A-adrenergic receptor subtype. However, it remains unknown if the efficacy and safety of naftopidil in Japanese is applicable to white, black and Hispanic men having LUTS/BPH in western countries. PMID:21753885
Alpha-adrenoceptor antagonists (?-blockers) are efficacious in treating lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO), also termed symptomatic benign prostatic hyperplasia (BPH), causing bladder outlet obstruction (BOO). There is little difference among the various ?-blockers in terms of efficacy in treating LUTS. However, conventional quinazoline derivatives such as terazosin, doxazosin and alfuzosin, originally developed for hypertension, have
Christian de Mey
The aquaporin (AQP) families of water channels are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. The purposes of this study were to determine the expression and localization of AQPs in benign prostatic hyperplasia and prostate cancer. Prostatic tissue was collected from patients with benign prostatic hyperplasia or prostate cancer by transurethral resection of the prostate. The expression and cellular localization of the AQPs were determined in the human prostate by Western blot and immunohistochemistry. AQP1, 3, and 9 were expressed in the human prostate. Western blot analysis revealed bands at 28-36 kDa for the AQP1, 3, and 9 proteins. Of these proteins, AQP3 and 9 were expressed in the epithelium. Immunolabeling showed that AQP1 was mainly expressed in the capillaries and venules of the prostate, AQP9 was expressed in the cytoplasm of the epithelium, and AQP3 was mainly associated with the plasma membrane of the prostatic epithelium. Only AQP3 expression was localized in the cell membrane, and expressed AQP3 was translocated to the cytoplasm in prostate cancer. The epithelium in the human prostate expresses AQP3 and 9 proteins, and the capillaries and venules of the prostate express AQP1. Characterizing or modifying the expression of AQP3 may lead to an understanding of the role of the AQPs in human prostatic disease.
Hwang, Insang; Hwang, Eu-Chang; Song, Seung Hee; Lee, Hyun-Suk; Kim, Sun-Ouck; Kang, Taek-Won; Kwon, Dongdeuk; Park, Kwangsung
ObjectivesBenign prostatic hyperplasia (BPH), the most common benign tumor in men, consists of two components—static (enlargement regulated by androgens) and dynamic (smooth muscle contraction through alpha1-adrenergic receptors [alpha1-ARs]). Because medical therapy of BPH involves tissue androgen deprivation, we studied the influence of androgen deprivation and replacement on regulation of rat ventral prostate alpha1-ARs.
John P. Lacey; Craig F. Donatucci; David T. Price; Stella O. Page; Steffany A. L. Bennett; Martin P. Tenniswood; Debra A. Schwinn
Background Infection plays a role in the pathogenesis of many human malignancies. Whether prostate cancer (PCa) - an important health issue in the aging male population in the Western world - belongs to these conditions has been a matter of research since the 1970 s. Persistent serum antibodies are a proof of present or past infection. The aim of this study was to compare serum antibodies against genitourinary infectious agents between PCa patients and controls with benign prostate hyperplasia (BPH). We hypothesized that elevated serum antibody levels or higher seroprevalence in PCa patients would suggest an association of genitourinary infection in patient history and elevated PCa risk. Methods A total of 434 males who had undergone open prostate surgery in a single institution were included in the study: 329 PCa patients and 105 controls with BPH. The subjects' serum samples were analysed by means of enzyme-linked immunosorbent assay, complement fixation test and indirect immunofluorescence for the presence of antibodies against common genitourinary infectious agents: human papillomavirus (HPV) 6, 11, 16, 18, 31 and 33, herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (CMV), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Neisseria gonorrhoeae and Treponema pallidum. Antibody seroprevalence and mean serum antibody levels were compared between cases and controls. Tumour grade and stage were correlated with serological findings. Results PCa patients were more likely to harbour antibodies against Ureaplasma urealyticum (odds ratio (OR) 2.06; 95% confidence interval (CI) 1.08-4.28). Men with BPH were more often seropositive for HPV 18 and Chlamydia trachomatis (OR 0.23; 95% CI 0.09-0.61 and OR 0.45; 95% CI 0.21-0.99, respectively) and had higher mean serum CMV antibody levels than PCa patients (p = 0.0004). Among PCa patients, antibodies against HPV 6 were associated with a higher Gleason score (p = 0.0305). Conclusions Antibody seropositivity against the analyzed pathogens with the exception of Ureaplasma does not seem to be a risk factor for PCa pathogenesis. The presence or higher levels of serum antibodies against the genitourinary pathogens studied were not consistently associated with PCa. Serostatus was not a predictor of disease stage in the studied population.
ObjectivesTo compare the early follow-up and perioperative morbidity of photoselective vaporization (PVP) and transurethral resection of the prostate (TURP) in patients (pts.) suffering from lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).
Alexander Bachmann; Leander Schürch; Robin Ruszat; Stephen F. Wyler; Hans-Helge Seifert; Alexander Müller; Kurt Lehmann; Tullio Sulser
Summary. Objectives. To examine the efficacy of prostate-spec ific antigen and vari- ous parameters obtained by transrectal ultrasonography as predictors of acute urinary retention in patients with benign prostatic hyperplasia. Methods. Eighty-nine men with symptoms of benign prostatic hyperplasia were en- rolled in this study from February 2002 to June 2003. Among them, 21 patients presented with acute urinary retention.
Testosterone production surges during puberty and orchestrates massive growth and reorganization of the prostate gland, and this glandular architecture is maintained thereafter throughout adulthood. Benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCA) are common diseases in adulthood that do not develop in the absence of androgens. Our objective was to gain insight into gene expression changes of the prostate gland
Saravana Mohan Dhanasekaran; Atreya Dash; Ira P. Maine; Bharathi Laxman; Scott A. Tomlins; Anjana Menon; Mark A. Rubin; Arul M. Chinnaiyan
We assessed the ability of 31phosphorus (31P) transrectal magnetic resonance spectroscopy to characterize normal human prostates as well as prostates with benign and malignant neoplasms. With a transrectal probe that we devised for surface coil spectroscopy we studied 15 individuals with normal (5), benign hyperplastic (4) and malignant (6) prostates. Digital rectal examination, transrectal ultrasonography and magnetic resonance imaging were used to aid in accurate positioning of the transrectal probe against the region of interest within the prostate. The major findings of the in vivo studies were that normal prostates had phosphocreatine-to-adenosine triphosphate (ATP) ratios of 1.2 +/- 0.2, phosphomonoester-to-beta-ATP ratios of 1.1 +/- 0.1 and phosphomonoester-to-phosphocreatine ratios of 0.9 +/- 0.1. Malignant prostates had phosphocreatine-to-beta-ATP ratios that were lower (0.7 +/- 0.1) than those of normal prostates (p less than 0.02) or prostates with benign hyperplasia. Malignant prostates had phosphomonoester-to-beta-ATP ratios (1.8 +/- 0.2) that were higher than that of normal prostates (p less than 0.02). Using the phosphomonoester-to-phosphocreatine ratio, it was possible to differentiate metabolically malignant (2.7 +/- 0.3) from normal prostates (p less than 0.001), with no overlap of individual ratios. The mean phosphomonoester-to-phosphocreatine ratio (1.5 +/- 0.5) of prostates with benign hyperplasia was midway between the normal and malignant ratios, and there was overlap between individual phosphomonoester-to-phosphocreatine ratios of benign prostatic hyperplasia glands with that of normal and malignant glands. To verify the in vivo results, we performed high resolution magnetic resonance spectroscopy on perchloric acid extracts of benign prostatic hyperplasia tissue obtained at operation and on a human prostatic cancer cell line DU145.
Narayan, P.; Jajodia, P.; Kurhanewicz, J.; Thomas, A.; MacDonald, J.; Hubesch, B.; Hedgcock, M.; Anderson, C.M.; James, T.L.; Tanagho, E.A. (Univ. of California School of Medicine, San Francisco (USA))
Androgen and estrogen play an important role in the pathogenesis of benign prostatic hyperplasia (BPH). Estrogen exerts its action through two distinct estrogen receptors (ERs) either ER-? or ER-?. The phytoestrogenic property of silymarin (SIL) has been previously characterized. Thus, this study examined the protective effect of SIL against testosterone-induced BPH in rats. In an initial dose-response study, SIL in a dose of 50mg/kg was the most effective in preventing the rise in prostate weight, prostate weight/body weight ratio and histopathologic changes induced by testosterone. Testosterone significantly decreased ER-? and increased ER-? and AR expressions as compared to the control group and these effects were significantly ameliorated by SIL. Furthermore, SIL significantly protected against testosterone-provoked decline in mRNA expression of P21(WAF1/Cip1) and Bax/Bcl-xl ratio as well as caspase-3 activity. SIL minimized the number of proliferating cell nuclear antigen (PCNA) positive cells as compared to testosterone-treated group. Moreover, SIL significantly blunted the inducible NF-?B expression and restored the oxidative status to within normal values in the prostatic tissues. Collectively these findings elucidate the effectiveness of SIL in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its phytoestrogenic, pro-apoptotic and anti-oxidative properties. PMID:23500659
Atawia, Reem T; Tadros, Mariane G; Khalifa, Amani E; Mosli, Hisham A; Abdel-Naim, Ashraf B
We investigated the add-on effect of dutasteride (0.5 mg once a day) on lower urinary tract symptoms (LUTS), prostate volume (PV), and serum prostate specific antigen (PSA) and testosterone level in 72 patients with benign prostatic hyperplasia (BPH) who had been treated with alpha-blocker monotherapy. Inclusion criteria were men with BPH who had PV ?30 ml and international prostate symptom score (IPSS) ?8 or quality of life (QOL) index ?3 under alpha-blocker monotherapy for more than 3 months. At the baseline, 12 and 24 weeks after dutasteride add-on, we assessed IPSS, overactive bladder symptom score (OABSS), PV, serum PSA and testosterone. Among 47 patients (65%) with OAB diagnosed by OABSS, responders were defined as those with urgency score of OABSS ?2 or total score of OABSS ?3. At the 24th week, dutasteride significantly improved IPSS (-4.2) and OABSS (-1.9) and reduced PV (-29%) compared with the baseline. Furthermore, dutasteride significantly decreased serum PSA (-45%) and increased testosterone (36%). Among OAB patients, dutasteride significantly improved urgency and urgency incontinence but not nocturia. Responders had lower OABSS, urgency incontinence score and serum testosterone at the baseline than non-responders. In conclusion, dutasteride add-on therapy is beneficial in patients with BPH who do not show enough improvement with alpha-blocker monotherapy. PMID:23070385
Wada, Naoki; Hashidume, Kazumi; Tamaki, Gaku; Kita, Masafumi; Iwata, Tatsuya; Matsumoto, Seiji; Kakizaki, Hidehiro
The examination of 648 males aged 50 to 86 to conduct an early outpatient detection of renal dysfunction in the elderly men employed an original technique of renal function assessment based on the kinetics of urinary 5-NOK elimination. Renal dysfunctions were revealed in 165 patients, in 159 of them the underlying cause was benign prostatic hyperplasia. The results were compared with those obtained at radionuclide tracing and Reberg-Tareev test. The correlation found indicated the authors' technique informative value and its compatibility with the above methods. Identification of renal dysfunction at early stages of benign prostatic hyperplasia allowed their timely hospitalization and operative treatment which enables the physicians to prevent progression of chronic renal failure in these patients. PMID:9461783
Rodoman, V E; Avdoshin, V P; Andriukhin, M I
Purpose Combination therapy of ?-blockers and 5?-reductase inhibitors (5-ARIs) is widely used for the treatment of benign prostatic hyperplasia (BPH). We aimed to study the effect on prostate volume and symptoms of shifting to monotherapy in patients who previously received a combination therapy. Materials and Methods A prospective study was conducted of 60 patients who were diagnosed with BPH. Patients were aged 45 years or older and had a prostate volume of 30 cc or more, International Prostate Symptom Score (IPSS) of 12 or above, maximal flow rate (Qmax) of 15 ml/s or less, and prostate-specific antigen (PSA) level of less than 10 ng/ml. The patients initially received a combination therapy of doxazosin 4 mg/day and finasteride 5 mg/day for 3 months and were then randomly assigned to receive monotherapy for 3 months. The factors were then compared. Results A total of 30 patients were assigned to doxazosin (group 1) and 30 to finasteride (group 2) after the combination therapy. The percentage changes in prostate volume, IPSS, and Qmax during the period from post-combination therapy to post-monotherapy were not significantly different between the two groups (p=0.052, 0.908, 0.081), whereas PSA significantly decreased in group 2 (p<0.001). IPSS was not significantly different at post-combination therapy and at post-monotherapy in both groups (p=0.858, 0.071). The prostate volume significantly increased from 40.97 cc at post-combination therapy to 44.29 cc at post-monotherapy in group 1 (p=0.001) and insignificantly increased from 38.32 cc to 38.61 cc in group 2 (p=0.696). Conclusions Although the duration of drug administration was short in this study, 5-ARI monotherapy could maintain the alleviated symptoms and reduce the risk of acute urinary retention and surgery due to prostate regrowth in BPH patients whose symptoms improved with combination therapy.
Kim, Hyoung Woo; Moon, Dae Geun; Kim, Hyun Min; Hwang, Jong Ho; Kim, Soon Chan; Nam, Sam Geuk
Introduction: According to previous studies, aging, gender, bladder volume and pathological states, such as bladder outflow obstruction, affect bladder wall thickness (BWT). The aim of this study was to evaluate the correlation between BWT and the International Prostatic Symptom Score (IPSS) in patients with benign prostatic hyperplasia (BPH) before and after tamsulosin treatment. Methods: In this study, 60 BPH patients were included. After obtaining informed consent, data were gathered using questionnaires to determine IPSS. After that, prostate-specific antigen was measured and a clinical examination, including a digital rectal examination, was performed for all patients. BWT was determined by transabdominal ultrasound. Finally, all patients were treated with tamsulosin (0.4 mg/day) for 2 months. After completing treatment, the IPSS and BWT were measured again and compared with the initial findings. Results: In total, 44 patients completed treatment. Patients aged 61.7 ± 9.2 years old. The mean ± standard deviation of IPSS and BWT were 14.6 ± 5.0 and 5.36 ± 1.28 mm before treatment, while they significantly (p < 0.0001) decreased to 8.2 ± 4.7 and 4.69 ± 1.23 mm, respectively, after treatment. Chi-square test showed that the decrease in BWT was significantly correlated with the improvement in IPSS (p = 0.002; r = 0.449). Conclusion: After treatment with tamsulosin, patients experienced a reduction in their BWT which was significantly correlated with improvement in their IPSS. We conclude that transabdominal evaluation of BWT could be included in the follow-up assessment in BPH.
Eghbali, Kamyar; Shayegan, Mohammad Reza; Kianoush, Sina
Dihydrotestosterone (DHT) is the primary metabolite of testoster- one in the prostate and skin. Testosterone is converted to DHT by 5-reductase, which exists in two isoenzyme forms (types 1 and 2). DHT is associated with development of benign prostatic hyperpla- sia (BPH), and reduction in its level with 5-reductase inhibitors improves the symptoms associated with BPH and reduces the risk
RICHARD V. CLARK; DAVID J. HERMANN; GLENN R. CUNNINGHAM; TIMOTHY H. WILSON; BETSY B. MORRILL; STUART HOBBS
Throughout the past decade, numerous techniques for the treatment of benign prostatic hyperplasia have emerged. Laser therapy, in particular, has gained widespread popularity among urologists. Since its inception in 1996, holmium laser enucleation of the prostate (HoLEP) has been evaluated rigorously in the treatment of glands of all sizes. HoLEP has produced superior relief of bladder outlet obstruction as compared to transurethral resection of the prostate based on urodynamics, and has proved equally as effective as open prostatectomy, for the management of very large glands (>100 cc), with lower morbidity. In addition to HoLEP, several newer but less well-studied laser techniques currently are available. These include photoselective laser vaporization utilizing the potassium-titanyl-phosphate (KTP or "green light") laser, thulium laser enucleation, and high-power diode laser vaporization. This report reviews the most current literature on laser therapies utilized in the treatment of benign prostatic hyperplasia with regards to safety, outcome, efficiency, and long-term durability. PMID:21088938
Mandeville, Jessica; Gnessin, Ehud; Lingeman, James E
Benign prostatic hyperplasia (BPH) represents a significant burden in ageing men due to frequently associated lower urinary tract symptoms (LUTS), which may impair quality of life. BPH is also a progressive disease, mainly characterized by a deterioration of LUTS over time, and in some patients by the occurrence of serious outcomes such as acute urinary retention (AUR) and need for BPH-related surgery. The goals of therapy for BPH are not only to improve bothersome LUTS but also to identify those patients at risk of unfavourable outcomes, to optimize their management. In selected patients, combination of an alpha(1)-blocker and a 5alpha-reductase inhibitor is the most effective form of BPH medical therapy to reduce the risk of clinical progression and relieve LUTS. Monotherapy also significantly reduces the risk of BPH clinical progression, mainly through a reduction of LUTS deterioration for alpha(1)-blockers while 5alpha-reductase inhibitors also reduce the risk of AUR and need for BPH-related surgery. Enlarged prostate and high serum prostate-specific antigen levels have been consistently found to be good clinical predictors of AUR and BPH-related surgery in longitudinal population-based studies and placebo arms of controlled studies. High post-void residual urine (PVR) is also associated with an increased risk of LUTS deterioration and should thus be reconsidered in practice as a predictor of BPH progression. Conversely, baseline LUTS severity and low peak flow rate, initially identified as predictors of unfavourable outcomes in community setting, behave paradoxically in controlled trials, probably as a consequence of strict inclusion criteria and subsequent regression to the mean and glass ceiling effects. Lastly, there is increasing evidence that dynamic variables, such as LUTS and PVR worsening, and lack of symptomatic improvement with alpha(1)-blockers are important predictors of future LUTS/BPH-related events, allowing better identification and management of patients at risk of BPH progression. PMID:18307681
Roehrborn, Claus G
Recent studies have indicated that the prostate-specific antigen (PSA) gene polymorphisms may be associated with the risk of prostate cancer in Caucasian populations. To verify the association, we examined the PSA polymorphisms at positions ?158 and ?252 in 300 prostate cancer cases, 216 benign prostatic hyperplasia (BPH) cases, and 266 controls by the PCR-restriction fragment length polymorphism analysis. Regarding the
Li-Zhong Wang; Kazunari Sato; Norihiko Tsuchiya; Jian-Gang Yu; Chikara Ohyama; Shigeru Satoh; Tomonori Habuchi; Osamu Ogawa; Tetsuro Kato
Background In our recent study, Periostin was up-regulated in prostate cancer(PCa) compared with benign prostate hyperplasia (BPH) by\\u000a proteomics analysis of prostate biopsies. We investigated the effect of sliencing Periostin by RNA interference (RNAi) on\\u000a the proliferation and migration of PCa LNCap cell line.\\u000a \\u000a \\u000a \\u000a \\u000a Methods All the prostate biopsies from PCa, BPH and BPH with local prostatic intraepithelial neoplasm(PIN) were analyzed by
Chuanyu Sun; Xiaojun Zhao; Ke Xu; Jian Gong; Weiwei Liu; Weihong Ding; Yuancheng Gou; Guowei Xia; Qiang Ding
Vatastheela is a disease of Mutravahasrotasa, one among the 12 types of Mutraghata disorders elaborated by Sushruta in his seminal work, the Sushruta Samhita. Vatastheela, as described in Ayurveda, closely resembles benign prostatic hyperplasia (BPH) of modern medicine in its signs and symptoms. It is a senile disorder and chiefly affects individuals above the age of 40 years. The symptoms are those of bladder outflow obstruction, with increased frequency of micturition, dribbling, hesitancy, and the features of chronic urinary retention. Surgical management has been accepted as the standard management but is associated with many disadvantages as well as complications, which may not be acceptable at this age. Conservative management with modern medicines is also not free from side effects. So, in this age-group, there is a need for much safer alternative method of management. In this regard, many works have been carried out and shown that the Ayurvedic approach, using natural medicines, is a far better approach. We carried out a comparative study of Mahayavanala Roma Kshara (MRK) and Dhanyaka Gokshura Ghrita (DGG), which are the compounds prescribed for Mutraghata in Ayurvedic literature. The patients were randomly selected from the OPD and IPD of IPGT and RA hospital, Jamnagar, Gujarat, and divided into two groups. In first group, one (500 mg) capsule of MRK was given twice a day with lukewarm water for 45 days; in second group, 10 gm of DGG was given orally twice a day with lukewarm water for 45 days. DGG showed significantly greater relief in the subjective parameters as per International Prostate Symptoms Score (IPSS) than MRK. However, reduction in the size of the prostate and in the volume of the post-void residual urine was found much better in the MRK group. PMID:22131735
Vasava, Yogesh R; Bhuyan, Chaturbhuja; Rajagopala, Manjusha; Gupta, S K; Dudhamal, T S
This study was conducted for qualitative analysis of serum proteins separated by SDS-PAGE and stained by Coomassie Brilliant Blue R-250 in order to describe the preliminary identification of serum proteins that may act as diagnostic marker in benign prostatic hyperplasia. Serum samples of 23 biopsy confirmed cases of benign prostatic hyperplasia and normal controls of similar age group were subjected
Saima Naz; Sarah Ahmad; Farkhanda Ghafoor
Benign prostatic hyperplasia (BPH) can significantly impair quality of life in older men. Most men over 60 experience some symptoms due to BPH and it is thought that essentially all men would eventually be affected by it if they lived long enough. At present, transurethral resection of the prostate (TURP), a surgical treatment for BPH, is one of the more common procedures performed in the developed world, particularly in the United States. A number of other treatments are also often used, including open prostatectomy, side-firing lasers, and drug therapy. With the population in the developed world rapidly aging, BPH is expected to affect an even larger group of men in the future. Current methods of therapy carry significant disadvantages. Open prostatectomy carries a fairly high risk of impotence and incontinence, as well as sometimes significant risk of death depending on the patient's age and medical conditions. TURP also carries similar risks, albeit reduced, including the risk of substantial blood loss and a small but meaningful risk of death. Side-firing lasers are thought to have a reduced risk of death compared to TURP due to significantly reduced bleeding; however, patients often experience an extended period of pain during voiding due to prolonged tissue sloughing. Drug treatment, although useful for some patients, does not strongly improve symptoms in the majority of patients. Even with the current range of treatments, many patients with symptomatic BPH elect to avoid any current treatment due to risks and side effects. As a possible solution to this problem, previous writers have suggested the possibility of treating BPH through interstitial thermotherapy. In this treatment, prostatic tissue is heated from within the prostate to the point of irreversible necrosis. Healing processes then reduce the volume of the affected tissue, even in the absence of sloughing. This study covers initial human use of such a device, using an 810 nm wavelength diode laser not previously used for such therapy.
Conn, Richard L.; Muschter, Rolf; Adams, Curtis S.; Esch, Victor C.
Holmium laser enucleation of the prostate (HoLEP) is a minimally invasive procedure and a size-independent treatment for benign prostatic hyperplasia with excellent long-term surgical outcome. HoLEP has become an alternative to conventional transurethral resection of the prostate or open prostatectomy owing to its efficacy and safety. Although HoLEP is known to have a steep learning curve, very few articles have addressed the technical aspects of HoLEP. Herein, we described detailed techniques and tips for HoLEP as performed at Seoul National University Hospital in a step-by-step manner with extensive review of the literature.
Kim, Myong; Lee, Hahn-Ey
Although ethnicity-based differences in prostate size and physiology have been reported, results of benign prostatic hyperplasia (BPH) treatment trials in predominantly Caucasian patients are assumed to be applicable to non-Caucasian populations. This post hoc analysis investigated whether an Asian subpopulation of men with moderate-to-severe BPH in the CombAT study achieves treatment responses in line with those of the overall study
B-H Chung; C G Roehrborn; P Siami; K Major-Walker; B B Morrill; T H Wilson; F Montorsi
Benign prostate hyperplasia (BPH) is the most common benign tumor in elderly men for which the HPC2/ELAC2 and SRD5A2 genes are known genetic factors. The HPC2/ELAC2 gene features Ser217Leu and Ala541Thr polymorphisms and the SRD5A2 gene Ala49Thr and Val89Leu polymorphisms. The aim of this study was to examine relationships between these polymorphisms and BPH in Turkish men using amplification by the polymerase chain reaction (PCR) method. Polymorphisms were determined by using restriction fragment length polymorphism (RFLP) with suitable restriction: TaqI?, Fnu4HI, Mwo I and Rsa I. We found statistically significant relationship between the SRD5A2 gene Ala49Thr (OR=2.3; CI 95%, 1.04-5.1; p=0.01<0.05) , but not the other polymorphisms, and BPH. For the first time, our data demonstrate that the correlation between SRD5A2 gene Ala49Thr and polymorphisms is statistically significant in Turkish men with BPH. PMID:21627373
Izmirli, Muzeyyen; Arikan, Burhan; Bayazit, Yildirim; Alptekin, Davut
Nocturia is one of the most bothersome complaints in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS\\/BPH). This is probably due to the fact that nocturia interferes with the quality of sleep which may have a significant negative impact on how the patient feels the next day in terms of energy level, concentration and mood and
Emmanuel Chartier-Kastler; Andrea Tubaro
Objectives. To investigate the long-term efficacy and safety of tamsulosin in patients with benign prostatic hyperplasia and to monitor the increases and decreases in therapeutic response over time. Tamsulosin, a uroselective alpha-adrenergic receptor antagonist for the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia, targets alpha1A-adrenergic receptors of prostatic smooth muscle with greater affinity than the vascular
Perinchery Narayan; Herbert Lepor
BACKGROUND: Claudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3, has been shown to be overexpressed in breast, ovarian, and pancreatic cancer. Here we use immunohistochemistry to evaluate its expression in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), normal tissue adjacent to prostatic adenocarcinoma (NAC), primary prostatic adenocarcinoma
Tanner L Bartholow; Uma R Chandran; Michael J Becich; Anil V Parwani
The development of age-related proliferative disorders of the prostate gland is supported by transdifferentiation and cellular senescence processes in the stroma. Both processes are involved in remodeling of stromal tissue, as observed in benign prostatic hyperplasia (BPH), and in “reactive stroma” adjacent to prostate cancer (PCa). It has been assumed that TGF-?1 plays a key role in the aging prostate
Gerold Untergasser; Roland Gander; Claudia Lilg; Günter Lepperdinger; Eugen Plas; Peter Berger
In elderly men, benign prostatic hyperplasia (BPH) is a major risk factor for sexual dysfunctions (SDys). Additionally, the standard treatments for BPH symptoms, alpha blockers and 5-alpha-reductase inhibitors, cause SDys themselves. Preparations from saw palmetto berries are an efficacious and well-tolerated symptomatic treatment for mild to moderate BPH and have traditionally been used to treat SDys. We conducted an open multicentric clinical pilot trial to investigate whether the saw palmetto berry preparation Prostasan® influenced BPH symptoms and SDys. Eighty-two patients participated in the 8-week trial, taking one capsule of 320?mg saw palmetto extract daily. At the end of the treatment, the International Prostate Symptom Score was reduced from 14.4?±?4.7 to 6.9?±?5.2 (p?0.0001); SDys measured with the brief Sexual Function Inventory improved from 22.4?±?7.2 to 31.4?±?9.2 (p?0.0001), and the Urolife BPH QoL-9 sex total improved from 137.3?±?47.9 to 195.0?±?56.3 (p?0.0001). Investigators' and patients' assessments confirmed the good efficacy, and treatment was very well tolerated and accepted by the patients. Correlation analyses confirmed the relationship between improved BPH symptoms and reduced SDys. This was the first trial with saw palmetto to show improvement in BPH symptoms and SDys as well. [Corrections made here after initial online publication.] PMID:22522969
Suter, Andreas; Saller, Reinhard; Riedi, Eugen; Heinrich, Michael
Background Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to ?1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study. Methods Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received ?1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the ?1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon. Results The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P?=?0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P?=?0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P?=?0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events. Conclusions Ramelteon in combination with an ?1-blocker could be a treatment option for reducing nocturia in men with BPH.
We report on two patients with symptomatic Benign Prostatic Hyperplasia (BPH) who were submitted to balloon dilation of the prostate. The symptoms and signs of prostatism markedly improved in both patients; however, the observed improvement did not correlate with the transrectal ultrasound findings of the results of the urinary flow studies. This is a preliminary report of an ongoing prospective protocol. PMID:1714266
Rodríquez Duarte, C
Summary \\u000a After the initial enthusiasm subsided lasercoagulation of the prostate has been criticized because the extent of tissue destruction\\u000a cannot be controlled and many patients may be expected to have significant postoperative obstructive as well as irritative\\u000a voiding symptoms which may last for weeks. Thanks to new laservaporization techniques these disadvantages have been largely\\u000a eliminated. With the Holmium laser a
W. Hochreiter; C. Hugonnet; U. E. Studer
Background As an alternative to transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP) provides a bloodless, relatively painless relief of lower urinary tract symptoms for men with benign prostatic hyperplasia. Following a review of the evidence in 2006, the Ontario Health Technology Advisory Committee recommended that a study be conducted to evaluate PVP in Ontario. Objectives To compare the clinical effectiveness, safety, cost-effectiveness, and budget impact of PVP compared to conventional TURP for the treatment of benign prostatic hyperplasia in Ontario. Methods A prospective, nonrandomized trial was conducted in 3 Ontario centres. Consenting subjects were assessed at baseline and 1, 3, and 6 months following surgery. Outcome measures included International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), post-void residual (PVR) volume, prostate-specific antigen (PSA), health-related quality of life (HRQOL) using the EuroQol 5 Domain questionnaire, and the Sexual Health Inventory for Men (SHIM) score. Adverse events, resource utilization, and productivity losses were also assessed. Cost-effectiveness and budget impact analyses were completed using data from the study. Results Between February 2008 and August 2010, 164 subjects were enrolled in the study (n = 140 for PVP and n = 24 for TURP). Treatment outcomes were similar between the 2 groups at 6 months, with the IPSS decreasing similarly over time (P = 0.718). For other treatment outcomes (Qmax, PSA, HRQOL, SHIM) both treatments provided similar benefit over time; only changes in PVR volume favoured PVP (P = 0.018). The majority of PVP patients were managed on an outpatient basis, with only 7.1% requiring admission (all TURP subjects were inpatients). At 6 months, PVP was less costly than TURP ($3,891 versus $4,863; P = 0.001), with similar quality-adjusted life-years (0.448 versus 0.441; P = 0.658). PVP remained the most cost-effective treatment across all decision-making thresholds, with the technology costing less and providing similar clinical outcomes. Extrapolating the results to a provincial level indicated (based on an estimated case volume of 12,335 TURPs) that there is an opportunity to reallocate just over $14 million (Cdn), primarily related to the reduced need for hospital admission. Limitations This study was nonrandomized, and the results should be interpreted with some caution, despite generally similar baseline characteristics between the 2 groups. Recruiting individuals to the TURP arm was a challenge, resulting in a size imbalance between treatment arms. Conclusions Based on this analysis, PVP appears to be a cost-effective alternative to TURP, providing similar clinical benefit at a lower cost to the health system. Plain Language Summary For men with lower urinary tract symptoms due to an enlarged prostate, a laser treatment called photoselective vaporization of the prostate (or PVP) is just as effective as surgery. PVP does not require an overnight stay in the hospital for most men, and it costs almost $1,000 less. This report describes the results of a study that collected information about treatment outcomes, quality of life, and health care use related to PVP and surgery in Ontario.
Bowen, James M.; Whelan, J. Paul; Hopkins, Robert B.; Burke, Natasha; Woods, Edward A.; McIsaac, Gary P.; O'Reilly, Daria J.; Xie, Feng; Sehatzadeh, Shayan; Levin, Leslie; Mathew, Suja P.; Patterson, Lisa L.; Goeree, Ron; Tarride, Jean-Eric
Purpose. To present our experience of prostate abscess management by modified transurethral resection (TUR) technique. Methods. Seventeen men with prostate abscess undergoing TUR between 2003 and 2011 were retrospectively analyzed. Details of demography, surgical procedures, complications, and followup were noted. Results. With a mean age of 61.53 ± 8.58 years, all patients had multifocal abscess cavities. Initially, 6 men underwent classical TUR similar to the technique used for benign prostatic enlargement (group 1). Next, 11 men underwent modified TUR (group 2) in which bladder neck and anterior zone were not resected. The abscess cavities resolved completely, and no patient required a second intervention. One patient in group 1 and three in group 2 had postoperative fever requiring parenteral antibiotics (P = 0.916). Three patients in group 1 had transient urinary incontinence, whereas none of the patients in group 2 had this complication (P = 0.055). Four and five men in group 1 and 2 reported retrograde ejaculation, respectively (P = 0.740). Conclusion. The modified technique of prostate resection edges over conventional TURP in the form of reduced morbidity but maintains its high success rate for complete abscess drainage. It alleviates the need for secondary procedures, having an apparent advantage over limited drainage techniques. Use of this technique is emphasized in cases associated with BPH and lack of proper preoperative imaging. PMID:23840969
Goyal, Neeraj Kumar; Goel, Apul; Sankhwar, Satyanarayan; Dalela, Divakar
Purpose This study was conducted with the use of 12 months of follow-up data to evaluate the efficacy of photoselective vaporization of the prostate (PVP) with the 980-nm diode laser for the treatment of symptomatic benign prostatic hyperplasia (BPH). Materials and Methods The clinical data of 84 men with symptomatic BPH who underwent PVP with the 980-nm K2 diode laser between March 2010 and October 2011 were retrospectively analyzed. Postoperative parameters, including International Prostate Symptom Score (IPSS), quality of life (QoL) score, maximum urinary flow rate (Qmax), and postvoid residual volume (PVR), were assessed and compared with preoperative baseline values. Results Mean patient age was 72.4±6.5 years, and mean preoperative prostate volume was 47.2±16.3 g. Mean operative time was 23.3±19.1 minutes, and total amount of energy was 128±85 kJ. Mean catheterization time was 23.7±5.9 hours. At 1 month, significant improvements were noted in IPSS (11.5±6.8), QoL score (2.2±1.3), Qmax (12.9±6.5 mL/s), and PVR (41.2±31.3 mL). Three months after surgery, all postoperative follow-up parameters showed significant improvements, and the 6- and 12-month data showed sustained improvement of postoperative follow-up parameters. Bladder neck strictures were observed in 10.7% of the patients and urge incontinence in 16.6%. Conclusions PVP using a K2 diode laser is an effective procedure for the treatment of lower urinary tract symptoms secondary to BPH. PVP leads to an immediate and sustained improvement of subjective and objective voiding parameters. Surgeons should be vigilant for postoperative bladder neck stricture and urge incontinence.
Kim, Youngho; Kim, In Gon; Han, Bo Hyun
Human monocyte chemoattractant protein-1 (MCP-1) has been shown to act as a chemokine in the recruitment of monocyte/macrophages during inflammation states. Furthermore, there is increasing evidence that MCP-1 is involved in the recruitment of tumor-associated macrophages. In vivo, one of the major cellular sources of MCP-1 are the smooth muscle cells. As MCP-1 gene expression and/or protein production in these cells is not necessarily correlated with the accumulation of inflammatory cells, there might possibly be additional functions of this cytokine. In the present study, we investigated by use of 35S-labeled antisense RNA probes whether the MCP-1 gene is expressed in tissue specimens of benign prostatic hyperplasia (n = 13) and specimens of prostate carcinoma (n = 8), both of which are characterized by a prominent fibromuscular stroma and inconspicuous inflammatory infiltrates. MCP-1 transcripts were located in stromal smooth muscle cells and, additionally, in basal cells of benign prostatic glands. In prostate carcinoma, the number of MCP-1 mRNA-expressing cells was significantly less than in benign prostatic hyperplasia. MCP-1 transcripts were located in preserved fibromuscular stroma and in basal cells of entrapped non-neoplastic glands but not in carcinomatous cells. Immunohistochemical staining with polyclonal antibodies raised against MCP-1 revealed strong reactivity in the fibromuscular stroma surrounding both benign and malignant glands. MCP-1 gene expression or immunoreactivity for anti-MCP-1 antibodies was not related to the rare, lymphocytic interstitial infiltrates. The results show that 1) in the absence of significant leukocyte accumulation, it is unlikely that MCP-1 exerts chemotactic functions in the prostate and 2) that MCP-1, in contrast to previous findings in a wide variety of other human neoplasms, is not expressed in carcinomatous cells of the prostate. Images Figure 2 Figure 3 Figure 4
Mazzucchelli, L.; Loetscher, P.; Kappeler, A.; Uguccioni, M.; Baggiolini, M.; Laissue, J. A.; Mueller, C.
This review discusses the available evidence concerning the use of anticholinergic drugs, alone or in combination with ?-adrenoceptor\\u000a antagonists, in men with lower urinary tract symptoms due to benign prostatic hyperplasia, benign prostatic enlargement, or\\u000a benign prostatic obstruction and concomitant overactive bladder syndrome. We emphasize the safety and efficacy of anticholinergic\\u000a agents in treating men with benign prostatic obstruction. Several
Kyu-Sung Lee; Hye Won Lee; Deok Hyun Han
Prostate cancer (PC) and benign prostate hyperplasia (BPH) constitute many of the health concerns of males around the world.\\u000a Prostate cancer is the major cause of death after lung cancer in men. Benign prostate hyperplasia affects most males above\\u000a 40 years of age. A variety of factors, chiefly age, genetics and lifestyle, have been linked to the development of PC and
Chukwunonso E. C. C. Ejike
Patient preference for benign prostatic hyperplasia (BPH) treatment with the ?(1)-blockers, tamsulosin or silodosin, was compared using patient-reported outcomes. Japanese patients with lower urinary tract symptoms associated with BPH were randomly allocated to either the T-S group (tamsulosin 0.2 mg orally once daily for 4 weeks then silodosin 4 mg orally twice daily for 4 weeks) or the S-T group (silodosin 4 mg orally twice daily for 4 weeks then tamsulosin 0.2 mg orally once daily for 4 weeks). The primary endpoint was the preferred drug for treatment continuation at 8 weeks, determined by a patient-reported questionnaire. In total, 102 patients (mean age 70.3 years) were enrolled and 84 (n = 42 per group) completed the study. A significant difference was observed between the proportion of patients who preferred tamsulosin (59/84 patients; 70.2%) and those who preferred silodosin (18/84 patients; 21.4%). A major reason for preference of either drug was 'good efficacy'. Incidence of adverse effects was significantly lower with tamsulosin (3/91 patients; 3.3%) than with silodosin (25/88 patients; 28.4%). These findings indicate that tamsulosin is very effective for BPH, has few adverse effects and that patients want to continue to use it. PMID:21672315
Watanabe, T; Ozono, S; Kageyama, S
Although nocturia has been recognised as one of the most bothersome symptoms in men suffering from lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS\\/BPH), its impact on quality of life (QoL) is often underestimated. Recent studies have shown a substantial negative effect of nocturia on quality of sleep, energy\\/vitality and social functioning. In addition, it has been shown
Christopher R. Chapple; Jose E. Batista; Richard Berges; Emmanuel Chartier-Kastler; Andrea Tubaro; Philip Van Kerrebroeck; Herman Stoevelaar
Saw Palmetto Berry Extract (SPBE) is applied for prostate health and treatment of urinary tract infections, nonbacterial prostitis and Benign Prostatic Hyperplasia (BPH) in man. An assumption is that SPBE affects tumor cell progression and migration in breast and prostate tissue. In this work, DU-145 cells were used to demonstrate that SPBE and its sterol components, ?-sitosterol and stigmasterol, inhibit
Carina Scholtysek; Aleksandra A. Krukiewicz; Jose´-Luis Alonso; Karan P. Sharma; Pal C. Sharma; Wolfgang H. Goldmann
The aim of our study was to assess the frequency and location of apoptotic bodies (ABs) in haematoxylin and eosin-stained sections of prostatic intra-epithelial neoplasia (PIN) and then to compare the patterns with those in benign prostatic hyperplasia (BPH) and prostatic invasive adenocarcinoma (PAC). ABs were identified in all epithelial cell layers of the ducts, acini and tumour islands, as
Rodolfo Montironi; Cristina Magi Galluzzi; Marina Scarpelli; Ioannis Giannulis; Lucilla Diamanti
Holmium laser enucleation (HoLEP) was developed in the 1990s as a more efficient and cost effective method of benign prostatic hyperplasia surgery than laser vaporization and resection techniques. As a true anatomical enucleation it mimics open prostatectomy and is as durable. There is a significant body of level 1 evidence in support of HoLEP, including 2 meta-analyses and 14 randomized trials which compare HoLEP with a number of other procedures. This review describes the development of and summarizes the evidence for HoLEP. PMID:24082919
Aho, Tevita F
Holmium laser enucleation (HoLEP) was developed in the 1990s as a more efficient and cost effective method of benign prostatic hyperplasia surgery than laser vaporization and resection techniques. As a true anatomical enucleation it mimics open prostatectomy and is as durable. There is a significant body of level 1 evidence in support of HoLEP, including 2 meta-analyses and 14 randomized trials which compare HoLEP with a number of other procedures. This review describes the development of and summarizes the evidence for HoLEP.
Photoselective vaporization of the prostate (PVP) with a potassium titanyl phosphate (KTP) laser may be the most promising\\u000a new technology applied to the treatment of benign prostatic hyperplasia (BPH). The specific laser light characteristics and\\u000a the ideal interactions between KTP lasers and prostatic tissue result in an even and efficient vaporization of the prostate\\u000a and the formation of a clearly
Petros Sountoulides; Jean J. M. C. H. de la Rosette
To evaluate the short and mid-term results of prostatic artery embolization in patients with benign prostatic embolization. Retrospective study between March 2009 and June 2011 with 103 patients (mean age 66.8 years, 50-85) that met our inclusion criteria with symptomatic benign prostatic hyperplasia. The clinical outcome was evaluated by the International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function, prostate volume (PV), prostate-specific antigen (PSA), peak urinary flow (Q(max)), and post-void residual volume (PVR) measurements at 3 and 6 months, 1 year, 18 months, and 2 years after PAE and comparison with baseline values was made. Technical and clinical successes, as well as poor clinical outcome definitions, were previously defined. In this review, we evaluate the short and mid-term clinical outcomes and morbidity of patients treated only with non-spherical polyvinyl alcohol. Six months after the procedure, the PV decreased about 23%, IPSS changed to a mean value of 11.95 (almost 50% reduction), the QoL improved slightly more than 2 points, the Q(max) changed to a mean value of 12.63 mL/s, the PVR underwent a change of almost half of the baseline value, and the PSA decreased about 2.3 ng/mL. In the mid-term follow-up and comparing to the baseline values, we still assisted to a reduction in PV, IPSS, QoL, PVR, and PSA, and an increase in Q(max). Prostatic Artery Embolization is a safe procedure with low morbidity that shows good short- and mid-term clinical outcome in our institution. PMID:23244726
Rio Tinto, Hugo; Martins Pisco, João; Bilhim, Tiago; Duarte, Marisa; Fernandes, Lúcia; Pereira, José; Campos Pinheiro, L
Purpose To evaluate the significance of intravesical prostatic protrusion (IPP) for predicting postoperative outcomes in patients with benign prostatic hyperplasia. Materials and Methods A total of 177 patients with a possible follow-up of at least 6 months who were treated with transurethral resection of the prostate (TURP) were analyzed. We divided the patients into two groups on the basis of the degree of IPP: the significant IPP group (IPP?5 mm, n=74) and the no significant IPP group (IPP<5 mm, n=103). We analyzed postoperative changes in parameters, such as the International Prostate Symptom Score (IPSS), IPSS quality-of-life (QoL) score, maximum urinary flow rate (Qmax), and postvoid residual urine (PVR). The IPSS was subdivided into voiding (IPSS-v) and storage (IPSS-s) symptoms. Multivariate logistic regression analysis was performed to identify whether IPP could predict surgical outcomes of TURP. Results Preoperative parameters were not significantly different between the two groups except for total prostate volume and transitional zone volume. Postoperative changes in IPSS, IPSS-v, IPSS-s, and QoL score were higher in the significant IPP group than in the group with no significant IPP. Changes in Qmax and PVR were not significantly different between the two groups. Multivariate logistic regression analysis (after adjustment for age, prostate-specific antigen level, total prostate volume, and transitional zone volume) revealed that the odds ratios (95% confidence interval) of decreased IPSS and IPSS-s in the significant IPP group were 3.43 (1.03 to 11.44) and 3.51 (1.43 to 8.63), respectively (p=0.045 and 0.006, respectively). Conclusions Significant IPP is an independent factor for predicting better postoperative outcomes of IPSS and IPSS-s.
Lee, Jong Woo; Ryu, Jae Hyun; Yoo, Tag Keun; Byun, Seok Soo; Jeong, Young Jin
We compared the efficacy, safety, and patient preferences for two ?1-adrenoceptor (AR) antagonists with different affinity for AR subtypes, naftopidil (Naf) and silodosin (Silo), for the treatment of male lower urinary tract symptoms associated with benign prostatic hyperplasia (male LUTS/BPH). New patients diagnosed with male LUTS/BPH were randomly divided into either the Naf-Silo group or the Silo-Naf group (Naf : 50-75 mg once daily for 2 weeks followed by 75 mg once daily for 4 weeks ; Silo : 2-4 mg twice daily for 2 weeks followed by 4 mg twice daily for 4 weeks). A survey was conducted to evaluate patient drug preferences after completion of the study and the reasons for the preferences. Naf and Silo improved the total International Prostate Symptom Score (IPSS) compared with baseline. There was no significant difference between Naf and Silo in improvement in the IPSS total score. Adverse effects were more frequent with Silo than with Naf (P=0. 002). No significant difference in patient preference for the drugs was observed. These findings indicate that Naf and Silo provide similar clinical efficacy, with no difference in patient preference for the drugs, although adverse effects were significantly more frequent with Silo than with Naf. PMID:23328162
Masuda, Mitsunobu; Jinza, Shin-ichirou; Masuko, Hiroshi; Asakura, Tomoyuki; Hashiba, Takafumi
Background Acu-point specificity is a key issue in acupuncture. To date there has not been any satisfactory trial which can ratify the specific effect of acupuncture. This trial will evaluate the specific effect of BL33 for mild and moderate benign prostatic hyperplasia (BPH) on the basis of its effectiveness. The non-specific effect will be excluded and the therapeutic effect will be evaluated. Method This is a double-blinded randomized controlled trial. 100 Patients will be randomly allocated into the treatment group (n = 50) and the control group (n = 50). The treatment group receives needling at BL33 and the control group receives needling at non-point. The needling depth, angle, direction, achievement of De Qi and parameters of electroacupuncture are exactly the same in both groups. The primary outcome measure is reduction of international prostate symptom score (IPSS) at the 6th week and the secondary outcome measures are reduction of bladder residual urine, increase in maximum urinary flow rate at the 6th week and reduction of IPSS at the 18th week. Discussion This trial will assess the specific therapeutic effect of electroacupuncture at BL33 for mild and moderate BPH. Trial registration Protocol Registration System of Clinical Trials.gov NCT01218243
The plants from the Lepidium gender have demonstrated to have effect on the size of the prostate. Lepidium meyenii (Maca) is a Peruvian plant that grows exclusively over 4000 m above sea level. The present study was designed to determine the effect of red maca (RM) in the prostate hyperplasia induced with testosterone enanthate (TE) in adult mice. Prostate hyperplasia was induced by administering TE, and then these animals (n = 6, each group) were treated with RM or Finasteride (positive control) for 21 days. There was an additional group without prostate hyperplasia (vehicle). Mice were killed on days 7, 14 and 21 after treatment with RM. Testosterone and oestradiol levels were measured on the last day of treatment. Prostatic stroma, epithelium and acini were measured histologically. RM reduced prostate weight at 21 days of treatment. Weights of seminal vesicles, testis and epididymis were not affected by RM treatment. The reduction in prostate size by RM was 1.59 times. Histological analysis showed that TE increased 2-fold the acinar area, effect prevented in the groups receiving TE + RM for 14 (P < 0.05) and 21 (P < 0.05) days and the group receiving TE + Finasteride for 21 days (P < 0.05). TE increased prostatic stroma area and this effect was prevented by treatment with RM since 7 days of treatment or Finasteride. The reduction in prostatic stroma area by RM was 1.42 times. RM has an anti-hyperplastic effect on the prostate of adult mice when hyperplasia was induced with TE acting first at prostatic stromal level. PMID:18477205
Gonzales, G F; Gasco, M; Malheiros-Pereira, A; Gonzales-Castañeda, C
Traditional medicine is very popular in Africa and it is considered as an alternative form of health care. Plants and vegetables used in folk and traditional medicine have gained wide acceptance as one of the main sources of prophylactic and chemopreventive drug discovery and this is due to the evidence of particular biological and biochemical characteristics of each plants extracts. The role of these compounds in urological field may be explained by the antiinflammatory effect through interference with prostaglandin metabolism, alteration of lipid peroxidation, direct inhibition of prostate growth and moreover through an antiandrogenic or antiestrogenic effect and a decrease of the availability of sex hormone-binding globulin. Since Benign Prostatic Hyperplasia and Prostate Cancer are two of the most diffuse diseases of aging male and considering that standard medical therapy is accompanied with different side effects, the emerging use of African plants may be justified. This review takes a look at some African plants extracts properties and their relative urological application. Different biomolecular mechanisms of action are promising, suggesting a real application in reducing prostate cells proliferation. PMID:23713889
Russo, Giorgio I; Cimino, Sebastiano; Salamone, Costanza; Madonia, Massimo; Favilla, Vincenzo; Castelli, Tommaso; Morgia, Giuseppe
We examined whether the effects (efficacy on the urethra and hypotension) of silodosin (alpha(1A)-adrenoceptor antagonist) and tamsulosin (alpha(1A+1D)-adrenoceptor antagonist) in dogs with benign prostatic hyperplasia altered with age. We used young and old dogs, diagnosed as having benign prostatic hyperplasia by veterinarian's palpation. Under anesthesia, the increase in intraurethral pressure evoked by hypogastric nerve stimulation was measured, together with the level of systemic mean blood pressure. Each drug was administered intravenously in progressively increasing doses. At the end of the experiment, the prostate was isolated from each dog, then weighed and investigated pathologically to confirm benign prostatic hyperplasia. The wet weight of the prostate was greater in old dogs with benign prostatic hyperplasia than in young dogs with benign prostatic hyperplasia. By light microscopy, hyperplasia in the prostatic epithelium was confirmed in both groups. Silodosin (0.3-300 microg/kg) dose-dependently inhibited the hypogastric nerve stimulation-induced increase in intraurethral pressure (without significant hypotensive effects) in both young and old dogs with benign prostatic hyperplasia. Tamsulosin (0.3-300 microg/kg) also dose-dependently inhibited the intraurethral pressure increase in both groups, but it had a hypotensive effect that was significantly greater in old than in young dogs with benign prostatic hyperplasia. In conclusion, as regards the effect of silodosin on intraurethral pressure, potency was similar between young and old dogs with benign prostatic hyperplasia, and it was without significant hypotensive effects. We therefore suggest that silodosin might be a good medication for lower urinary tract symptoms in patients with benign prostatic hyperplasia in all age groups. PMID:19389393
Kobayashi, Shinya; Tomiyama, Yoshitaka; Tatemichi, Satoshi; Hoyano, Yuji; Kobayashi, Mamoru; Yamazaki, Yoshinobu
Objective: To determine the effect of an interactive multimedia prostate education program (MMP) on self assessment of symptom scores due to benign prostatic hyperplasia (BPH). Methods: The interactive MMP was developed including a computer-administered version of the International Prostate Symptom Score (IPSS) questionnaire. Eighty-eight men referred to the Urology Out-patients with prostatic symptoms entered the study. They first completed the
P. van Schaik; T. Ahmed; N. Suvakovic; J. R. Hindmarsh
Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa), but in the critical diagnostic range of 4 -10 ng\\/ml it has limited specificity for distinguishing early PCa from benign pros- tatic hyperplasia (BPH). PSA in serum is comprised of a variety of both \\
Stephen D. Mikolajczyk; Lisa S. Millar; Tang J. Wang; Harry G. Rittenhouse; Leonard S. Marks; Weitao Song; Thomas M. Wheeler; Kevin M. Slawin
We conducted this study to investigate whether CAG repeat length in androgen receptor gene and GSTM1 and GSTT1 polymorphisms\\u000a influence prostate cancer risk in Iranian newly diagnosed cancer patients compared to age-matched BPH group and healthy individuals.\\u000a DNA from 110 pathologically-confirmed prostate cancer patients, 99 age-matched men with Benign Prostatic Hyperplasia (BPH)\\u000a and 100 healthy individuals were extracted and amplified
Zahra Ousati Ashtiani; Sayed-Mohammad Hasheminasab; Mohsen Ayati; Bareto Sabah Goulian; Mohammad Hossein Modarressi
Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) will usually affect older men, of whom 50% over the age 60 years and almost 90% in their nineties will be bothered enough by their symptoms that they request some type of treatment. However, symptomatic bother may also affect men in their forties with a prevalence rate of almost 18%. The International Prostate Symptom Score (IPSS) has become the most widely used and best validated questionnaire to allow the patient to quantify the severity of his LUTS/BPH symptoms. This score has become the cornerstone in demonstrating the "rate of symptom response" for the patient who has been exposed to any type BPH management. Question 8 on the IPSS score is what is defined as the "Quality of Life" question or what is also termed the "Bothersome Index." The score out of 6 as declared by the patient will reflect the degree of concern that the patient is feeling about his symptoms and the reduction of the score after treatment is a statement of their improved quality of life. There are 2 families of accepted medical therapy to treat the symptoms of BPH and potentially prevent the most worrisome long-term sequelae of progression of BPH: urinary retention or the need for surgery. When defining the impact of the main types of medical therapy, the alpha blockers have been termed the "openers" and the 5 alpha-reductase inhibitors are described as the "shrinkers." Since they each offer a different mechanism of effect, the concept of combination therapy was raised and trialed many times over recent years. The final aspect of any medical therapy is the patient's satisfaction with the treatment and the side effects. In the CombAT (Combination of Avodart and Tamsulosin) trial a new assessment was developed and tested called the Patient's Perception of Study Medication (PPSM) which told the investigators if the patients, given free choice, would choose to take that combination of medication to treat their problem and stay on the medication. PMID:22003286
Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) will usually affect older men, of whom 50% over the age 60 years and almost 90% in their nineties will be bothered enough by their symptoms that they request some type of treatment. However, symptomatic bother may also affect men in their forties with a prevalence rate of almost 18%. The International Prostate Symptom Score (IPSS) has become the most widely used and best validated questionnaire to allow the patient to quantify the severity of his LUTS/BPH symptoms. This score has become the cornerstone in demonstrating the “rate of symptom response” for the patient who has been exposed to any type BPH management. Question 8 on the IPSS score is what is defined as the “Quality of Life” question or what is also termed the “Bothersome Index.” The score out of 6 as declared by the patient will reflect the degree of concern that the patient is feeling about his symptoms and the reduction of the score after treatment is a statement of their improved quality of life. There are 2 families of accepted medical therapy to treat the symptoms of BPH and potentially prevent the most worrisome long-term sequelae of progression of BPH: urinary retention or the need for surgery. When defining the impact of the main types of medical therapy, the alpha blockers have been termed the “openers” and the 5 alpha-reductase inhibitors are described as the “shrinkers.” Since they each offer a different mechanism of effect, the concept of combination therapy was raised and trialed many times over recent years. The final aspect of any medical therapy is the patient’s satisfaction with the treatment and the side effects. In the CombAT (Combination of Avodart and Tamsulosin) trial a new assessment was developed and tested called the Patient’s Perception of Study Medication (PPSM) which told the investigators if the patients, given free choice, would choose to take that combination of medication to treat their problem and stay on the medication.
Canine and human prostates were treated with high intensity focused ultrasound (HIFU) using a transrectal probe. Near the beam focus, temperatures were shown to be greater than 60°C, while periprostatic tissue temperatures increased ⩽3°C; rectal wall temperatures did not rise more than 5°C over the baseline. In 15 patients with benign prostatic hyperplasia (BPH), no major complications resulted from HIFU
N. T. Sanghvi; R. S. Foster; R. Bihrle; F. J. Fry; M. Phillips; C. Hennige
Objective: The short and long-term effects of two common transurethral procedures (TURP and TULP, transurethral prostatic resection and laser prostatectomy, respectively) on plasma hormone levels in patients with benign prostatic hyperplasia (BPH) have been evaluated. Patients and Methods: Totally 57 patients with histologically proven BPH (age range 54–81 years, mean 62.5 years) were included into the study program. Of these
Kadir Türkölmez; Murat Bozlu; Kemal Sarica; Hakan Gemalmaz; Erol Özdiler
The objective of this study was to test the hypothesis that prostatic cancer is associated with the changes of zinc (Zn) and\\u000a cadmium (Cd) concentration. Normal prostate, benign prostatic hyperplasia (BPH), and prostatic carcinoma (PCA) were analyzed\\u000a for Zn and Cd by atomic absorption spectrometry. Cd level was measured using a graphite furnace and Zn level was measured\\u000a by flame
Magdalena Brys; Agnieszka D. Nawrocka; Eügeniüsz Mleko?; Cezary Zydek; Marek Foksinski; Andrzej Barecki; Wanda M. Krajewska
We investigated the optimum initial dose and timing of administration of ?1A-adrenoceptor antagonist silodosin for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH/LUTS). Ninety-eight patients were given a 4 mg dose after breakfast (group A), 4 mg after supper (group B), or 4 mg after breakfast and after supper (group C). At baseline, 4, 8 and 12 weeks after treatment, we assessed International Prostate Symptom Score (IPSS) and quality of life (QOL) index. Twenty-five percent or less improvement of total IPSS and no improvement of QOL index compared with baseline were defined as treatment failure at each evaluation point. Otherwise treatment was considered effective. In group A and group B, patients with treatment failure at 4 or 8 weeks after treatment, the dose of silodosin was increased to 8 mg daily. At the end of the study, 83 patients were evaluable. At 12 weeks after treatment, 20 of the 31 patients in group A and 22 of the 29 patients in group B remained on the 4 mg dose ; silodosin was effective in 65 and 76% of the patients, respectively. When patients with dose escalation were included, silodosin was effective in 81 and 90% of the patients, respectively. Silodosin was effective in 18 of the 23(78%) patients in group C, although improvement of total IPSS and voiding symptom score of IPSS at 12 weeks after treatment was better in group C than in group A or group B, the difference was not significant. In patients with IPSS less than 20, the degree of improvement of IPSS was similar among the 3 groups. In contrast, in patients with IPSS of 20 or greater the degree of improvement was better in group C than in group B or group C, but the difference was not significant. Storage symptom score of IPSS was significantly improved in all 3 groups without any significant difference among the 3 groups. Three patients (52, 59 and 76 years old) experienced abnormal ejaculation. In conclusion, 4 mg of silodosin daily showed effectiveness against BPH/LUTS, but 8 mg of silodosin daily might be better for patients with severe LUTS. PMID:21795831
Wada, Naoki; Numata, Atsushi; Yamaguchi, Satoshi; Osanai, Hiroaki; Mori, Tatsuya; Hou, Kyokushin; Fujisawa, Makoto; Kaneko, Shigeo; Kakizaki, Hidehiro
Trans-urethral resection of the prostate (TURP) and other minimally invasive therapies are the most common surgical procedures used to treat benign prostatic hyperplasia today. However, many patients with a markedly enlarged prostate are often not amenable to these treatment options. In these patients open prostatectomy has been representing a viable and preferred treatment. Despite the morbidity of open enucleation is substantial, until recently no other options were available when the size of the prostate approached 100 g and beyond. The use of holmium laser for the treatment of benign prostatic hyperplasia was first reported in 1996. Holmium laser enucleation of the prostate (HoLEP) has been proposed as an alternative to TURP and to open prostatectomy for patients with lower urinary tract symptoms (LUTS) due to large benign prostatic enlargement. In this manuscript, the development of HoLEP from the initial reports to the long-term follow-up data which demonstrate the effectiveness of the technique in treating patients affected by LUTS secondary to large adenomas has been reviewed. HoLEP seems to represent a valid alternative to both TURP and OP, with valid long-term functional results, a low rate of short-term and long-term complications, and very low rates of reintervention. In conclusion, HoLEP can be offered as the size-independent gold standard treatment of patients with LUTS due to benign prostatic enlargement. PMID:19773730
Suardi, N; Gallina, A; Salonia, A; Briganti, A; Cestari, A; Guazzoni, G; Rigatti, P; Montorsi, F
The major risk concern of testosterone replacement therapy in middle-aged and older men is that it may lead to an increase\\u000a in the incidence and severity of symptomatic benign prostatic hyperplasia (BPH) and prostate carcinoma. While this concern\\u000a is based on the role of androgens in the development and maintenance of these prostate diseases and the use of castration\\u000a to
J. Lisa Tenover
Minimally invasive therapies for treatment of benign prostatic hyperplasia (BPH) compete with the gold standard transurethral resection of the prostate (TURP). Comparisons of efficacy and safety have broadened the knowledge of different treatment modalities. Concerns of quality of life such as unaltered sexual function as well as cost considerations drive the market to develop techniques of lower level invasiveness. Among the competitors the office based transurethral microwave thermotherapy (TUMT) provides the broadest scale of scientific data. Numerous manufacturers sell various modifications of this technology. According to different clinical studies TUMT proved to be an effective, safe, and durable therapy for the treatment of lower urinary tract symptoms (LUTS) secondary to BPH. However, TURP still holds the steadier long-term results and is more effective to reduce obstruction as well as other LUTS. PMID:16752156
Herrmann, T R W; Gross, A J; Schultheiss, D; Kaufmann, P M; Jonas, U; Burchardt, M
Even if transurethral resection of the prostate (TURP) today remains the referential surgery in the treatment of symptomatic benign prostatic hyperplasia (BPH), the last decade has seen the emergence of considerable improvements in light amplification by stimulated emission of radiation (LASER) technology. Better understanding of the interaction between the different wavelengths of these lasers and tissue has enabled the development of new and promising types of treatment. This article, through a review of published literature, attempts first of all to retrace the history of this technique in the treatment of symptomatic BPH and then goes on to give an update on results and new aspects of the different types of laser used. PMID:19268251
Fourmarier, M; Azzouzi, A-R; Robert, G; Saussine, C; Devonec, M; Haillot, O; Ballereau, C; Lukacs, B; de la Taille, A
High Intensity Focused Ultrasound (HIFU) has been clinically used for the treatment of benign prostatic hyperplasia (BPH) and it is experimentally applied for the treatment of localized prostate caner (PC). Recent advances in the transducer material and technology have permitted to combine the ultrasound visualization capability and HIFU on the same ceramic crystal. Also, the transducer efficiency has increased to
Narendra T. Sanghvi; J. Syrus; Richard S. Foster; Richard Bihrle; Richard W. Casey; Toyoak Uchida
Atypical adenomatous hyperplasia (AAH) is a distinct entity in prostate pathology, defined as a well-circumscribed lobule of closely packed crowded small glands or acini. Although it has been proposed as a precursor lesion to prostate cancer, the biological nature of AAH is currently uncertain. The TMPRSS2-ERG fusion gene is a common recurrent chromosomal rearrangement in prostate cancer and in its precursor lesion, prostatic intraepithelial neoplasia. The prevalence of TMPRSS2-ERG alteration in AAH is unknown. Fifty-five separate prostate specimens containing AAH were investigated by fluorescence in situ hybridization and immunohistochemistry for TMPRSS2-ERG rearrangement. TMPRSS2-ERG rearrangements were not identified in AAH either by fluorescence in situ hybridization or by immunohistochemistry. PMID:23887154
Cheng, Liang; Davidson, Darrell D; Maclennan, Gregory T; Lopez-Beltran, Antonio; Montironi, Rodolfo; Wang, Mingsheng; Tan, Puay-Hoon; Baldridge, Lee Ann; Zhang, Shaobo
ObjectivesTo assess the long-term safety and efficacy of dutasteride, a dual type 1 and type 2 5-?-reductase inhibitor, in the treatment of symptomatic benign prostatic hyperplasia and associated lower urinary tract symptoms.
Claus G Roehrborn; Leonard S Marks; Tom Fenter; Sheldon Freedman; John Tuttle; Marc Gittleman; Betsy Morrill; Eric T Wolford
Vaccaria seeds (Wang-Bu-Liu-Xing), a well-known traditional Chinese medicine (TCM), has been used as an emperor herb of many ancient formulas to treat benign prostatic hyperplasia (BPH) in clinic. However, its metabolism and tissue distribution, especially in the target tissue, had not been investigated so far. Based on the hypothesis that the components which exert effect against BPH of Vaccaria seeds would be measureable in target tissue (prostate), in vivo metabolism and tissue distribution of Vaccaria seeds in rats were profiled using a specific and sensitive high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (LC-QTOF-MS/MS). As a result, 19 major constituents in the Vaccaria seeds decoction and 19 constituents in rat plasma, feces and tissues after oral administration of Vaccaria seeds decoction were identified. Accurate mass measurement for molecular ions and characteristic fragment ions could represent reliable identification criteria for these compounds. Two prototypes were detected in prostate. An in vitro metabolism analysis of them was studied after incubation with rat intestinal flora and rat liver microsome (RLM) in this paper, which is helpful for further investigation of the potential effect of these two components. The result of this study provided meaningful information for further pharmacology research on Vaccaria seeds. PMID:23973757
Qi, Peng; Li, Zhixiong; Chen, Mingcang; Sun, Zhaolin; Huang, Chenggang
We examined whether the effects (efficacy on the urethra and hypotension) of silodosin (?1A-adrenoceptor antagonist) and tamsulosin (?1A+1D-adrenoceptor antagonist) in dogs with benign prostatic hyperplasia altered with age. We used young and old dogs, diagnosed as having benign prostatic hyperplasia by veterinarian's palpation. Under anesthesia, the increase in intraurethral pressure evoked by hypogastric nerve stimulation was measured, together with the
Shinya Kobayashi; Yoshitaka Tomiyama; Satoshi Tatemichi; Yuji Hoyano; Mamoru Kobayashi; Yoshinobu Yamazaki
Objective: Prospective randomized study to compare the efficacy and safety of alfuzosin and tamsulosin in patients suffering from acute urinary retention caused by benign prostatic hyperplasia (BPH). Methods: Patients with acute urinary retention (AUR) due to BPH (total 150) were catheterized and randomized into three groups: Group A: alfuzosin 10 mg (50 patients), Group B: tamsulosin 0.4 mg (50 patients), Group C: placebo (50 patients). After three days, catheter was removed, and patients were put on trial without catheter (TWOC). Patients with successful TWOC were followed up for three months, taking into account the prostate symptom score (AUA Score), post-void residual urine volume (PVRV), and peak flow rate (PFR). ANOVA was used for statistical analysis. Results: Both group A (alfuzosin) and group B (tamsulosin) had similar results of TWOC (group A – 66%, group B – 70%), which were significantly superior than group C (placebo) – 36%. In follow up, three (9.1%) patients in group A, three (8.6%) patients in group B and eight (44.4%) patients in group C had retention of urine, requiring recatheterization. These patients were withdrawn from the study. After three months, alfuzosin- or tamsulosin-treated patients showed a significant decrease in AUA score and PVRV; and a significant increase in PFR as compared to placebo. Conclusions: TWOC was more successful in men treated with either alfuzosin or tamsulosin and the subsequent need for recatheterization was also reduced. Tamsulosin was comparable to alfuzosin in all respects, except a small but significant side effect of retrograde ejaculation.
Agrawal, Madhu S.; Yadav, Abhishek; Yadav, Himanshu; Singh, Amit K.; Lavania, Prashant; Jaiman, Richa
Objectives To evaluate the safety profile and efficacy of ?1-adrenergic receptor blockers (A1Bs) currently prescribed for benign prostatic hyperplasia (BPH). Data sources A systematic literature search of MEDLINE, the Cochrane Database and the Food and Drug Administration Web site through December 2006 identified double-blinded, prospective, placebo-controlled trials, evaluating agents commercially available by prescription for the symptomatic treatment of BPH. Review methods Data were reviewed by two investigators with the use of a standardised data abstraction form. Studies were evaluated for methodological quality using the Jadad scale. Studies with a score of < 3 were considered of weaker methodology. Results Of 2389 potential citations, 25 were usable for evaluation of safety data, 26 for efficacy. A1B use was associated with a statistically significant increase in the odds of developing a vascular-related event [odds ratio (OR) 2.54; 95% confidence interval (CI): 2.00–3.24; p < 0.0001]. The odds of developing a vascular-related adverse event were: alfuzosin, OR 1.66, 95% CI: 1.17–2.36; terazosin, OR 3.71, 95% CI: 2.48–5.53; doxazosin, OR 3.32, 95% CI: 2.10–5.23 and tamsulosin, OR 1.42, 95% CI: 0.99–2.05. A1Bs increased Qmax by 1.32 ml/min (95% CI: 1.07–1.57) compared with placebo. Difference from placebo in American Urological Association symptom index/International Prostate Symptom Score was ?1.92 points (95% CI: ?2.71 to ?1.14). Conclusions Alfuzosin, terazosin and doxazosin showed a statistically significant increased risk of developing vascular-related events compared with placebo. Tamsulosin showed a numerical increase that was not statistically significant. All agents significantly improved Qmax and symptom signs compared with placebo.
Nickel, J C; Sander, S; Moon, T D
Prostate tissues from patients with prostate cancer and benign prostatic hyperplasia (BPH) frequently contain histological inflammation, and a proportion of these patients show evidence of Propionibacterium acnes infection in the prostate gland. We developed a multicolor fluorescent in situ hybridization (FISH) assay targeting P. acnes 23S rRNA along with a 14-kb region of the P. acnes genome. This assay was used to analyze prostate tissues from patients with prostate cancer and BPH. P. acnes infection of the prostate gland was demonstrated in prostatic tissue in 5 of 10 randomly selected prostate cancer patients. FISH analysis and confocal laser microscopy imaging revealed intracellular localization and stromal biofilm-like aggregates as common forms of P. acnes infection in prostate tissues from both prostate cancer and BPH patients. A sequential analysis of prostate tissue from individual patients suggested that P. acnes can persist for up to 6 years in the prostate gland. These results indicate that P. acnes can establish a persistent infection in the prostate gland. Further study is needed to clarify the link between this bacterium and prostatic inflammation which may contribute to the development of BPH and prostate cancer.
Alexeyev, Oleg A.; Marklund, Ingrid; Shannon, Beverley; Golovleva, Irina; Olsson, Jan; Andersson, Charlotte; Eriksson, Irene; Cohen, Ronald; Elgh, Fredrik
It appears that the technology for local microwave application of heat to the prostate for the management of benign prostatic hyperplasia has arrived. There are a number of issues to be resolved in the coming years that will determine the role this modality will play in the overall management of men with benign prostatic hyperplasia. These issues include: transurethral versus transrectal route, hyperthermia (42 degrees C to 44 degrees C) versus thermotherapy (greater than 45 degrees C), and a proper assessment as to whether the technique is really efficacious, given the known placebo response in all studies currently available. The results with the transrectal route appear to improve patients' symptoms objectively and subjectively, without causing irreversible tissue effects. Thus, its action has been likened to alpha blockade. But, it appears that the transrectal approach is relatively inefficient because of a significant loss in microwave power with rectal cooling. A probe placed transurethrally can accurately and easily deliver the intended power to the center of the prostate, where theoretically it has its greatest effect on both the dynamic and static components of outlet obstruction. Currently, the transurethral devices described by Sapozink and Devonec will produce histologic necrosis. The theoretical value of combining urethral heating with cooling is that it will allow treatments of greater power deeper in the prostate adenoma, but the greatest advantage over transurethral heating without cooling may be in the ability to effect a response in a single session. Finally, the placebo response is a well known phenomenon seen in all drug trials conducted for the management of benign prostatic hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1722800
Blute, M L; Lewis, R W
We examined the influence of different factors [benign prostatic hyperplasia (BPH), prostatic carcinoma (PCA), organ volume, weight of resected tissue, transurethral catheter] on the serum prostate-specific antigen (PSA) levels in 253 patients with BPH (n = 138; 54%) and PCA (n = 115; 46%). Only in 57.2% of the BPH patients, PSA values were < 4 ng/ml, in 74.6% < 7 ng/ml. In 108 patients with BPH, a transurethral prostatectomy was performed. PSA values correlated significantly with the sonographically determined prostatic volumes and less precisely with the weight of the resected tissue. The PSA concentration per milliliter of prostatic volume was 0.12 ng/ml, per gram of resected tissue it was 0.21 ng/ml. An incidental PCA was found in 12/108 patients (11%). The PSA values were identical with those of the total collective in regard to volume and tissue weight. In 11 patients, we examined possible alterations of the PSA values before and until 24 h after prostatic massage. Only insignificant alterations were seen, a massive increase was not found in any patient. Searching for an absolutely valid 'normal value' appears hardly appropriate. However, the usefulness of PSA is increased when the sonographically determined prostatic volume is included. A rectal examination of the prostate has no influence on the PSA value. PMID:1385141
Walz, P H; Schoppmann, T; Büscher, C; Ennen, J; Schriewer, H
Asian men have much lower incidences of prostate cancer and possibly of benign prostatic hyperplasia (BPH) than their Western counterparts. Vegetarian men also have a lower incidence of prostate cancer than omnivorous males. Both Asian and vegetarian men consume low-fat, high-fibre diets which provide a rich supply of weak dietary oestrogens. These plant or phyto-oestrogens have been proposed as chemopreventive
L. Denis; M. S. Morton; K. Griffiths
Construct validation of patient global impression of severity (PGI-S) and improvement (PGI-I) questionnaires in the treatment of men with lower urinary tract symptoms secondary to benign prostatic hyperplasia
Background Lower urinary tract symptoms (LUTS) in aging men are often associated with benign prostatic hyperplasia (BPH). While regulatory evaluations of treatment benefit require an assessment of specific symptoms, a simpler approach to measuring patients’ perceptions of severity and symptom change may be particularly useful for clinical practice. The aim of this study was to provide evidence of the validity of the 1-item Patient Global Impression of Severity (PGI-S) and Improvement (PGI-I) questionnaires for use as outcome measures in the treatment of BPH-LUTS. Methods This was a secondary analysis of data from 4 randomized placebo-controlled 12-week trials evaluating tadalafil for the treatment of BPH-LUTS (N=1694). Visit 2 (V2 [beginning of a 4-week placebo lead-in period]) and endpoint assessments included International Prostate Symptom Score (IPSS), IPSS Quality of Life Index (IPSS-QoL), BPH Impact Index (BII), and peak urine flow (Qmax). PGI-S was only administered at V2 and PGI-I only at endpoint. Associations between the PGI-S or the PGI-I and the other assessments were analyzed by calculating Spearman rank correlation coefficients and performing analysis of variance (ANOVA). Results Spearman correlation coefficients were 0.43, 0.43, 0.53, and ?0.09, between the PGI-S and IPSS, IPSS-QoL, BII, and Qmax baseline results (all P<0.001). Similar results were seen across race, ethnicity, and baseline severity (moderate LUTS versus severe LUTS). IPSS, IPSS-QoL, BII baseline scores (P <0.001) and Qmax values (P=0.003) were significantly different among the 4 PGI-S severity levels. Spearman correlation coefficients were 0.56, 0.53, 0.47 and ?0.15 between the PGI-I and change in IPSS, IPSS-QoL, BII scores, and Qmax values from baseline to endpoint (all P<0.001). Similar results were seen across race, ethnicity, and baseline severity. Change in IPSS, IPSS-QoL, BII scores, and Qmax values (P<0.001) were significantly different among the PGI-I levels (i.e., patient perception of change in urinary symptoms). Conclusions This study demonstrated patients’ overall perceptions of their severity and change in BPH-LUTS can be captured in a way that is simple, valid, and easily administered in a research setting or clinical practice. Clinical parameters are weakly associated with patients’ perception of urinary symptoms, emphasizing the importance of a patient-reported assessment in the evaluation of BPH-LUTS treatment benefit.
Background Interleukin-8 (IL-8) is upregulated in fibrotic and malignant diseases and is a key mediator of proliferative responses. Elevated IL-8 was recently correlated with benign prostatic hyperplasia epithelium and a myofibroblast reactive stroma. Thus, we sought to determine whether overexpressed IL-8 and keratinocyte-derived chemokine (KC), the functional murine homolog of IL-8, induce prostate epithelial hyperplasia and a reactive phenotype. Methods Transgenic mice that overexpress KC within prostate epithelia and xenograft models with engineered human cells that overexpress IL-8 were developed. Results Overexpression of KC in transgenic mice produced hyperplastic prostate epithelial acini associated with a periacinar reactive stroma. KC induced an altered epithelial/stroma proliferation index ratio, increased acini diameter, epithelial infolding, and expression of prototypical reactive stroma markers. Overexpression of IL-8 in normal human prostate epithelial xenografts correlated with elevated epithelial proliferation index and altered morphology. Elevated human prostate stromal and epithelial cell proliferation, nodule-like morphology and increased xenograft survival were observed in IL-8-overexpressing orthotopic xenografts. Conclusions Together, these data demonstrate that overexpression of IL-8/KC results in a prostate epithelial hyperplasia with an associated reactive stroma phenotype. The novel transgenic mouse and human xenograft models described here may be useful in dissecting key mechanisms of IL-8 induced prostate hyperplasia and reactive stroma.
Schauer, Isaiah G.; Ressler, Steven J.; Rowley, David R.
15-Lipoxygenase 2 (15-LOX2), a lipid-peroxidizing enzyme, is mainly expressed in the luminal compartment of the normal human prostate and often decreased or lost in prostate cancer. Previous studies from our lab implicate 15-LOX2 as a functional tumor suppressor. To better understand the biological role of 15-LOX2 in vivo, we established prostate-specific 15-LOX2 transgenic mice using the ARR2PB promoter. Unexpectedly, transgenic expression of 15-LOX2 or 15-LOX2sv-b, a splice variant that lacks the arachidonic acid metabolizing activity, resulted in age-dependent prostatic hyperplasia and enlargement of the prostate. Prostatic hyperplasia induced by both 15-LOX2 and 15-LOX2sv-b was associated with an increase in luminal and Ki-67+ cells; however, 15-LOX2-transgenic prostates also showed a prominent increase in basal cells. Microarray analysis revealed distinct gene expression profiles that could help explain the prostate phenotypes. Strikingly, 15-LOX2, but not 15-LOX2sv-b, transgenic prostate showed upregulation of several well-known stem/progenitor cell molecules including Sca-1, Trop2, p63, Nkx3.1 and Psca. Prostatic hyperplasia caused by both 15-LOX2 and 15-LOX2sv-b did not progress to prostatic intraprostate neoplasia (PIN) or carcinoma and, mechanistically, prostate lobes (especially those of the 15-LOX2 mice) showed a dramatic increase in senescent cells as revealed by increased SA-?gal, p27Kip1 and HP1? staining. Collectively, our results suggest that 15-LOX2 expression in mouse prostate leads to hyperplasia and also induces cell senescence, which may, in turn, function as a barrier to tumor development.
Suraneni, MV; Schneider-Broussard, R; Moore, JR; Davis, T Calhoun; Maldonado, CJ; Li, H; Newman, RA; Kusewitt, D; Hu, J; Yang, P; Tang, DG
This study examined efficacy and safety of the 980 nm side-firing diode laser operating at a power of 100 W in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). Patients were selected for surgery on the basis of maximum urinary flow rate (Qmax)
Background Benign prostatic hyperplasia affects older men. This systematic review determined efficacy and adverse effects of finasteride. Review methods PubMed, the Cochrane Library, reference lists of reports, and reviews were searched for randomised, double-blind trials of finasteride in benign prostatic hyperplasia. Outcomes included symptom score, urinary flow rate, prostate volume, discontinuation, and adverse effects. Relative risk and NNT or NNH were calculated for dichotomous data. Sensitivity analyses assessed influences of baseline symptom severity, initial prostate volume, a dominating trial, and previous interventions. Results Three trials had active controls and 19 had placebo. In placebo-controlled trials, 8820 patients received finasteride 5 mg and 5909 placebo over 3–48 months. Over 48 months finasteride produced greater improvements in total symptom score, maximum urinary flow rate, and prostate volume. Significantly more sexual dysfunction, impotence, ejaculation disorder and decreased libido occurred with finasteride at 12 months; the NNH for any sexual dysfunction at 12 months was 14. Significantly fewer men treated with finasteride experienced acute retention or had surgery at 24 or 48 months than with placebo; at 12 months the NNT was 49 (31 to 112) to avoid one acute urinary retention and 31 (21 to 61) to avoid one surgery. Sensitivity analyses showed benefit with finasteride 5 mg to be constant irrespective of the initial prostate volume. Conclusions Information from many patients in studies of high quality showed beneficial effects of finasteride in terms of symptoms, flow rate and prostate volume. More utility would result if patient centred outcomes were reported in dichotomous form.
Edwards, Jayne E; Moore, R Andrew
Background Androgen acts via androgen receptor (AR) and accurate measurement of the levels of AR protein expression is critical for prostate research. The expression of AR in paired specimens of benign prostate and prostate cancer from 20 African and 20 Caucasian Americans was compared to demonstrate an application of this system. Methods A set of 200 immunopositive and 200 immunonegative nuclei were collected from the images using a macro developed in Image Pro Plus. Linear Discriminant and Logistic Regression analyses were performed on the data to generate classification coefficients. Classification coefficients render the automated image analysis software independent of the type of immunostaining or image acquisition system used. The image analysis software performs local segmentation and uses nuclear shape and size to detect prostatic epithelial nuclei. AR expression is described by (a) percentage of immunopositive nuclei; (b) percentage of immunopositive nuclear area; and (c) intensity of AR expression among immunopositive nuclei or areas. Results The percent positive nuclei and percent nuclear area were similar by race in both benign prostate hyperplasia and prostate cancer. In prostate cancer epithelial nuclei, African Americans exhibited 38% higher levels of AR immunostaining than Caucasian Americans (two sided Student's t-tests; P < 0.05). Intensity of AR immunostaining was similar between races in benign prostate. Conclusion The differences measured in the intensity of AR expression in prostate cancer were consistent with previous studies. Classification coefficients are required due to non-standardized immunostaining and image collection methods across medical institutions and research laboratories and helps customize the software for the specimen under study. The availability of a free, automated system creates new opportunities for testing, evaluation and use of this image analysis system by many research groups who study nuclear protein expression.
Singh, Swaroop S; Kim, Desok; Mohler, James L
Objectives. Dutasteride, a dual 5?-reductase inhibitor, is used to treat benign prostatic hyperplasia. Nevertheless, its histopathological effects on the morphometrics of blood vessels and glands are still controversial. The aim here was to assess the histopathological effects of dutasteride in cases of benign prostatic hyperplasia in a retrospective study. Methods. Patients with benign prostatic hyperplasia more than 40?cm(3) in prostatic volume were administered 0.5?mg of dutasteride daily or left untreated prior to receiving a transurethral resection of the prostate. Images of sections stained with hematoxylin/eosin and with anti-CD31 antibody were analyzed. Results. In the dutasteride-treated group, the duration of administration was 16.3 ± 8.1 weeks. Artery/arteriole density and vein/venule density in benign prostatic tissue were both lower in the dutasteride-treated group than in the control group. The vein/venule area as a percentage of the whole area was also lower in the dutasteride-treated group, while the artery/arteriole area did not show a significant difference. Glandular/CD31-expressing vessel densities as well as glandular/CD31-expressing vessel areas were comparable between the two groups. Conclusions. Dutasteride reduced the artery/arteriole and vein/venule densities and the proportion of vein/venule area in the tissue of patients with benign prostatic hyperplasia. PMID:23401800
Zaitsu, Masayoshi; Tonooka, Akiko; Mikami, Koji; Hattori, Mami; Takeshima, Yuta; Uekusa, Toshimasa; Takeuchi, Takumi
Local biotransformation enzymes and transporter proteins in tissues may exert a profound effect on drug pharma- cokinetics in those tissues. Thus, the use of drugs for the treatment of benign prostatic hyperplasia (BPH) and can- cer of the prostrate may be influenced by high level ex- pression of cytochrome P450 (CYP) phase I and phase II conjugation enzymes and drug
REGINA OBLIGACION; MICHAEL MURRAY; IQBAL RAMZAN
The two drug types commonly used to treat symptoms of benign prostatic hyperplasia (BPH), 5?-reductase inhibitors and ?1-blockers, have been shown to have different long-term effects on outcomes such as incidence of acute urinary retention (AUR) and BPH-related surgery. In addition, a comparative study of ?1-blockers and 5?-reductase inhibitors in men with lower urinary tract symptoms showed that the treatment
C. G Roehrborn; T McNicholas
The diagnosis of prostate cancer is challenging because of the existence of lesions that mimic adenocarcinoma. Such a lesion is atypical adenomatous hyperplasia (AAH) or adenosis, which represents a proliferation of crowded, small to medium glands with basal cell layer invariably present, but often inconspicuous on routine stains. The importance of the lesion lies in the potential for being misdiagnosed as low-grade adenocarcinoma (Gleason 1 or 2). We present the case of a male patient, who suffered a transurethral prostatic resection surgery. Histopathological examination showed benign prostatic hyperplasia with a focus of crowded glands with a nodular appearance. The presence of basal cell was assessed using high molecular-weight cytokeratin (HMWCK), clone 34?E12 and p63 immunostaining, which revealed discontinuous positive immunostaining. In adenocarcinomas, the basal cell layer is absent. This case highlights the usefulness of 34?E12 antibodies, avoiding a false positive diagnosis of cancer, with negative consequences on the patient's psychological condition and treatment costs. We recommended the follow-up of the patient. PMID:23303039
Enciu, Manuela; A?chie, Mariana; Bo?oteanu, M?d?lina; Chisoi, Anca
Lasers have been used for symptomatic Benign Prostatic Hyperplasia (BPH) in both contact and non-contact modes with reported success rates equivalent to that of Transurethral Resection of Prostate (TURP). A new high power diode laser (Phototome), capable of delivering up to 50 watts of 1000 nm wavelength laser power via a 1 mm quartz fiber, was used to treat 15 patients with symptomatic BPH. Five patients had acute retention, 3 had long term catheter (7 - 48 months), and 8 had severe prostatism. Spinal anesthesia was used in 11 patients, and 4 patients had local anesthesia and intravenous sedation. Four quadrant coagulation with an angle firing probe delivering 50 watts of laser power for 60 seconds in one quadrant was used as the core of the treatment in 11 patients, contact vaporization of BPH tissue was performed in one patient using a 4.5 mm ball tip was used in one patient and three patients with bladder neck stenosis had bladder neck incision performed using a 1 mm quartz fiber delivering 30 watts of laser power. A foley catheter was left indwelling and removed after 5 - 7 days. All patients except one were catheter free after a mean of 8 days. One patient continued to have severe prostatism and had a TURP performed with good results after 3 months of his laser prostatectomy procedure. AUA symptom scores available in 11 patients was found to be 4 after 1 - 3 months of the initial procedure.
Bhatta, Krishna M.
Background Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is an adapter protein which has been shown to play an active role in\\u000a a wide variety of cellular processes, including interactions with proteins related to both tumor suppression and oncogenesis.\\u000a Here we use immunohistochemistry to evaluate EBP50's expression in normal donor prostate (NDP), benign prostatic hyperplasia\\u000a (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), normal tissue
Tanner L Bartholow; Michael J Becich; Uma R Chandran; Anil V Parwani
New therapeutic approaches have recently been investigated in order to improve the voiding disorders of patient with lower urinary tract symptoms related to benign prostatic hyperplasia. The purpose of this article is to provide a review of these treatments: anti-inflammatory, antidiuretic, anticholinergic and botulinum toxin. Anticholinergic drugs associated with a risk of urinary retention, appear to be effective for irritative disorders in combination with an alpha-blocker. Antidiuretics can be proposed in patients younger than 65 with disabling polyuria confirmed by a voiding diary, related to BPH and refractory to conventional treatment of BPH. The interaction between inflammation and BPH has not yet been clarified, but anti-inflammatory drugs appear to improve symptoms and may have a place in short-term treatment of BPH, as their long-term use is not recommended and COX-2 inhibitors have been withdrawn from the market. Finally, botulinum toxin could have a place in the treatment of disorders related to BPH if clinical studies confirm the recently published promising results. These new approaches will probably be integrated into guidelines and flow-charts for the treatment of voiding disorders related to BPH. PMID:17633985
De la Taille, Alexandre; Fourmarier, Marc; Desgrandchamps, Francois; Ballereau, Charles; Saussine, Christian; Haillot, Olivier; Azzouzi, Abdel-Rahmène; Lukacs, Bertrand; Devonec, Marian
Holmium laser resection of the prostate (HoLRP) was first described by Gilling et al in 1995. HoLRP has now evolved into holmium laser enucleation of the prostate (HoLEP) with the advent of the intravesical soft-tissue morcellator. The procedure involves anatomical dissection of the prostatic tissue off the surgical capsule in a retrograde fashion using a high-powered holmium laser followed by intravesical morcellation of the prostatic tissue. Some groups believe that the HoLEP procedure is the endoscopic equivalent to a simple open prostatectomy and may be superior to transurethral resection of the prostate (TURP) or even open prostatectomy. The objective of this article is to explain the techniques for holmium laser enucleation of the prostate (HoLEP). PMID:22316518
Kelly, Douglas C; Das, Akhil
The gold standard for symptomatic relief of bladder outlet obstruction secondary to benign prostatic hyperplasia has traditionally been a transurethral resection of the prostate (TURP). Over the past decade, however, novel laser technologies that rival the conventional TURP have multiplied. As part of the ongoing quest to minimize complications, shorten hospitalization, improve resection time, and most importantly reduce mortality, laser prostatectomy has continually evolved. Today, there are more variations of laser prostatectomy, each with several differing surgical techniques. Although abundant data are available confirming the safety and feasibility of the various laser systems, future randomized-controlled trials will be necessary to verify which technique is superior. In this review, we describe the most common modalities used to perform a laser prostatectomy, mainly, the holmium laser and the potassium-titanyl-phosphate lasers. We also highlight the physical and clinical characteristics of each technology with a review of the most current and highest-quality literature. PMID:23789041
Osterberg, E Charles; Choi, Benjamin B
Objectives. To investigate the long-term effects of finasteride on bother and health-related quality of life (HRQOL) in men with symptomatic benign prostatic hyperplasia.Methods. A large prospective 4-year placebo-controlled trial (PLESS) of 3040 men with moderate to severe lower urinary tract symptoms and an enlarged prostate was performed that included self-administered questionnaires assessing HRQOL.Results. Significantly greater reductions in bother score were
Reginald Bruskewitz; Cynthia J. Girman; Jackson Fowler; Odell F. Rigby; Michael Sullivan; R. Bruce Bracken; Harold A. Fusilier; Douglas Kozlowski; Scott D. Kantor; Edward Lee Johnson; Daniel Z. Wang; Joanne Waldstreicher
The oil of babassu tree nuts (Orbignya speciosa) is a potential alternative for treatment and prophylaxis of benign prostatic hyperplasia. Improved results can be obtained by drug vectorization to the hyperplastic tissue. The main objective of this work was the preparation and characterization of poly(lactic-co-glycolic acid) (PLGA) nanoparticle and clay nanosystems containing babassu oil (BBS). BBS was extracted from the kernels of babassu tree nuts and characterized by gas chromatography-mass spectrometry as well as 1H and 13C nuclear magnetic resonance. BBS-clay nanosystems were obtained by adding polyvinylpyrrolidone, Viscogel B8®, and BBS at a 2:1:1 mass ratio and characterized by X-ray diffraction, thermogravimetric analysis, infrared spectroscopy, and laser diffraction. The PLGA-BBS nanoparticles were prepared by the precipitation-solvent evaporation method. Mean diameter, polydispersity, zeta potential, and scanning electron microscopic images of the nanosystems were analyzed. Thermogravimetric analysis showed successful formation of the nanocomposite. PLGA nanoparticles containing BBS were obtained, with a suitable size that was confirmed by scanning electron microscopy. Both nanostructured systems showed active incorporation yields exceeding 90%. The two systems obtained represent a new and potentially efficient therapy for benign prostatic hyperplasia.
de Sousa, Valeria Pereira; Crean, Joanne; de Almeida Borges, Vinicius Raphael; Rodrigues, Carlos Rangel; Tajber, Lidia; Boylan, Fabio; Cabral, Lucio Mendes
Purpose To examine the efficacy and safety of holmium laser enucleation of the prostate (HoLEP) for the surgical treatment of benign prostatic hyperplasia and to estimate the time to overcome the learning curve. Materials and Methods From May 2008 to October 2009, 164 consecutive patients treated with HoLEP were enrolled in this study. International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and postvoid residual urine (PVR) were documented preoperatively and at 6 weeks and 3, 6, 12, and 18 months postoperatively. The 164 study subjects were divided into 3 groups (group 1 the first 50 patients treated, group 2 the second 50, and group 3 the third 64), and perioperative data and complications were analyzed in these groups to determine the learning curve. In addition, the inverse and upward techniques were compared in terms of the effects and the stability of morcellation. Results The mean patient age was 69 years, and the average operation time was 62 minutes (range, 20-208 minutes). Mean prostate volume was 54.2 ml and mean resected tissue weight was 18.6 g. Postoperatively, IPSS and PVR decreased and Qmax increased significantly. Postoperative complications were transient incontinence (8.5%), urinary retention (4.3%), hematuria (3.0%), urinary tract infection (1.2%), and urethral stricture (0.6%), and intraoperative complications were minor capsular perforation (4%) and bladder injury (8%). Conclusions HoLEP was found to be effective and safe regardless of prostate size. We recommend that a systematic educational program be established to reduce the learning curve.
Hwang, Jin Chul; Park, Sang Myung
Objective: To establish clinical efficacy and safety of High Intensity Focused Ultrasound (HIFU) for the treatment of benign prostatic hyperplasia (BPH) in a multiple site clinical study. Methods: Seven clinical sites were set up for the studies, five in the USA, one in Canada and one in Japan respectively. Sixty two patients were enrolled in these three studies. Transrectal ultrasound
N. T Sanghvi; R. S Foster; R Bihrle; R Casey; T Uchida; M. H Phillips; J Syrus; A. V Zaitsev; K. W Marich; F. J Fry
OBJECTIVE: To derive a formula that defines the postvoid residual (PVR) urine volume more accurately in patients with prostatic gland enlargement. DESIGN: Prospective. SETTING: Department of Radiology, University of Ilorin Teaching Hospital, Ilorin. SUBJECT: Fifty-two consecutive patients with benign prostatic hyperplasia. The mean age was 64.98+/-9.57 years. METHOD: PVR urine was evaluated by ultrasonography. Each patient had two examinations, the first of which was with a full bladder and the second of which was immediately after voiding. Two orthogonal diameters were measured on each bladder section (longitudinal and transverse) in the supine position. Fifty-two paired sets of ultrasonic measurements were thus obtained. Catheterized postvoid urine residue was regarded as the gold standard. RESULTS: Using these measurements, an equation--[PVR(CUBIC)=374.057+(-196.94+V1)+(32.5539+V1(2))+(-1.1480+V1(3)) where V1=average of the length (L), width (T), and the anteroposterior distance on transverse section (Dt) of the postvoid urinary bladder]--more accurate than previously existing ones was obtained by cubic regression analysis. Mean ultrasound estimated volume was 220.51 ml as against 220.76 ml after catheterization. The mean difference was 0.25 ml (not significant, p<0.01) with 95% confidence interval of +/-10 ml. With this equation, the ultrasonographic residual urine volume showed a higher correlation coefficient with the catheterized volume at p<0.01 (Pearson r=0.982, r2=0.96) than previously defined formulas. The standard error of the mean was 5.11 ml (mean=220.5+/-190.4 ml). CONCLUSION: With the above equation, we consider conventional transabdominal ultrasonography a reliable method for assessing the residual urine volume in patients with benign prostatic hyperplasia. This equation, though complex when compared to some of the pre-existing formulas, can be integrated into the memory of modern ultrasound machines for easy and faster computation. Images Figure 1
Amole, Adewumi O.; Kuranga, Sulyman A.; Oyejola, Benjamin A.
Interest in and use of complementary and alternative therapies, especially nutraceuticals, is high in prostate disease. These therapies have shown potential in benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer. Some have produced results equal to or better than pharmaceuticals currently prescribed for BPH. In category III prostatitis, some nutraceuticals may offer relief to patients who get little from standard therapy. Because it is becoming apparent that inflammation may play a role in the progression of BPH and development of prostate cancer, nutraceuticals, which commonly have anti-inflammatory properties, may play a role. These therapies have also shown potential in prostate cancer treatment and prevention, especially those that also reduce cardiovascular events or risk. Nevertheless, uses of some nutraceuticals in prostate disease have had less desirable consequences, showing lack of efficacy, adulteration, and/or severe side effects or drug interactions. By ensuring that these therapies undergo careful study for effectiveness, quality, and safety, urologists can look forward to adding them to their evidence-based armamentarium for prostate disease.
Curtis Nickel, J; Shoskes, Daniel; Roehrborn, Claus G; Moyad, Mark
We performed a retrospective, case-control study to evaluate whether the urine flow acceleration (UFA, mL/s(2)) is superior to maximum uroflow (Qmax, mL/s) in diagnosing bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH). In this study, a total of 50 men with BPH (age: 58±12.5 years) and 50 controls (age: 59±13.0 years) were included. A pressure-flow study was used to determine the presence of BOO according to the recommendations of Incontinence Control Society (ICS). The results showed that the UFA and Qmax in BPH group were much lower than those in the control group [(2.05±0.85) vs. (4.60±1.25) mL/s(2) and (8.50±1.05) vs. (13.00±3.35) mL/s] (P<0.001). According to the criteria (UFA<2.05 mL/s(2), Qmax<10 mL/s), the sensitivity and specificity of UFA vs. Qmax in diagnosing BOO were 88%, 75% vs. 81%, 63%. UFA vs. Omax, when compared with the results of P-Q chart (the kappa values in corresponding analysis), was 0.55 vs. 0.35. The prostate volume, post void residual and detrusor pressure at Qmax between the two groups were 28.6±9.8 vs. 24.2±7.6 mL, 60.4±1.4 vs. 21.3±2.5 mL and 56.6±8.3 vs. 21.7±6.1 cmH2O, respectively (P<0.05). It was concluded that the UFA is a useful urodynamic parameter, and is superior to Qmax in diagnosing BOO in patients with BPH. PMID:23904378
Wen, Jian-Guo; Cui, Lin-Gang; Li, Yi-Dong; Shang, Xiao-Ping; Zhu, Wen; Zhang, Rui-Li; Meng, Qing-Jun; Zhang, Sheng-Jun
Prostatic stents and microwave thermotherapy are minimally invasive techniques for the treatment of voiding disorders related to benign prostatic hyperplasia. A review of the literature evaluates the place of these treatments in 2006. Permanent prostatic stenting is rarely used, but remains a treatment option for patients with obstructive disorders and a formal anaesthetic contraindication. Temporary stenting can be used to predict the effect of resection in selected patients. Finally, microwave thermotherapy, not widely used in France, has a promising clinical efficacy and occupies a place between medical treatment and surgery. PMID:17175945
Saussine, Christian; Devonec, Marian; Haillot, Olivier; Fourmarier, Marc; Desgrandchamps, François; Ballereau, Charles; Azzouzi, Abdel-Rahmène; Lukacs, Bertrand; de la Taille, Alexandre
A leading role for prostatic levels of dihydrotestosterone (DHT) in the pathogenesis of benign prostatic hyperplasia is well established, if incompletely understood. The present study provides initial confirmation that 5 alpha-reductase inhibition alone is sufficient to prevent prostatic accumulation of DHT and to produce epithelial regression in the canine prostate. In dogs treated with the specific 5 alpha-reductase inhibitor finasteride, prostatic volume decreased to one-third of the baseline volume, while the prostatic concentration of DHT fell fivefold: both were constant in placebo control dogs. Demonstration that MR imaging can serve as accurate modality to assess prostatic volume was provided by serial measurements of the canine prostate and by correlation of the last imaging measurement with the weight of the excised prostate. Significant intensity changes were observed in T2-weighted images measured post-treatment; these changes correlated with the histopathology of the prostate. These results suggest that beyond quantifying regression, multiecho T2 measurements can be useful in probing accompanying changes occurring on the cellular level. PMID:1719333
Cohen, S M; Taber, K H; Malatesta, P F; Shpungin, J; Berman, C; Carlin, J R; Werrmann, J G; Prahalada, S; Bryan, R N; Cordes, E H
A Randomized Trial Comparing Holmium Laser Enucleation of the Prostate with Transurethral Resection of the Prostate for the Treatment of Bladder Outlet Obstruction Secondary to Benign Prostatic Hyperplasia in Large Glands (40 to 200 Grams)
PurposeHolmium laser enucleation of the prostate (HoLEP) is a surgical treatment for bladder outlet obstruction secondary to benign prostatic hyperplasia. HoLEP is a transurethral procedure that uses the holmium laser fiber (wavelength 2,140 nm) to dissect whole prostatic lobes off of the surgical capsule in retrograde fashion, while maintaining excellent hemostasis. The lobes are removed from the bladder by a
A. H. H. TAN; P. J. GILLING; K. M. KENNETT; C. FRAMPTON; A. M. WESTENBERG; M. R. FRAUNDORFER
The QT interval is the electrocardiographic manifestation of ventricular depolarization and repolarization. Drug-induced long QT syndrome is characterized by acquired, corrected QT (QTc) interval prolongation that is associated with increased risk of torsade de pointes. Every physician must recognize if the drugs he or she prescribes prolongs the QTc interval, especially if the drug is prescribed for a chronic condition in older patients who are on polypharmacy. The evolution of alpha-blockers for the treatment of benign prostatic hyperplasia has allowed the development of drugs that are easier to administer and better tolerated. Because alpha-blockers generally have equivalent efficacy, this class of drugs is typically differentiated by safety and side effects. Studies suggest that alpha-blockers may vary in regard to their effect on the QT interval, and, therefore, on their predisposition to cause potentially life-threatening ventricular arrhythmias.
Lepor, Herbert; Lepor, Norman E; Hill, Lawrence A; Trohman, Richard G
The usual treatments of benign prostate hyperplasia (BPH) including the alpha-blockers, the inhibitors of the 5-alpha reductase and the phytotherapy drugs allow significant improvements of the lower urinary tracts symptoms (LUTS). However, some patients are not responders or have side effects due to the treatments. Other therapeutic approaches described in the literature are possible in order to alleviate the LUTS. The anti-cholinergic drugs seem to be efficient against the irritating symptoms even if they are supposed to be contra-indicated when there is BPH. Anti-diuretic hormone could be useful to treat nocturia due to diuresis reversal. Inflammation is a part of the underlying mechanisms of BPH and as such the role of the anti-inflammatory drugs has to be revised. Eventually, botulinum toxin is more and more used for patients with neurological bladder and could also have a role in LUTS. If the coming clinical studies on those different treatments confirm the preliminary results, the learning societies in charge of the guidelines would have to update the decision trees by adding these new therapeutic approaches. PMID:16710668
Azzouzi, Abdel-Rahmène; Fourmarier, Marc; Desgrandchamps, Francois; Ballereau, Charles; Saussine, Christian; Haillot, Olivier; Lukacs, Bertrand; Devonec, Marian; de la Taille, Alexandre
Background Prostate cancer and benign prostatic hyperplasia are very common diseases in older American men, thus having a reliable treatment modality for both diseases is of great importance. The currently used treating options, mainly surgical ones, have numerous complications, which include the many side effects that accompany such procedures, besides the invasive nature of such techniques. Focused ultrasound is a relatively new treating modality that is showing promising results in treating prostate cancer and benign prostatic hyperplasia. Thus this technique is gaining more attention in the past decade as a non-invasive method to treat both diseases. Methods In this paper, the design, construction and evaluation of a 1.75 dimensional ultrasound phased array to be used for treating prostate cancer and benign prostatic hyperplasia is presented. With this array, the position of the focus can be controlled by changing the electrical power and phase to the individual elements for electronically focusing and steering in a three dimensional volume. The array was designed with a maximum steering angle of ± 13.5° in the transverse direction and a maximum depth of penetration of 11 cm, which allows the treatment of large prostates. The transducer piezoelectric ceramic, matching layers and cable impedance have been designed for maximum power transfer to tissue. Results To verify the capability of the transducer for focusing and steering, exposimetry was performed and the results correlated well with the calculated field. Ex vivo experiments using bovine tissue were performed with various lesion sizes and indicated the capability of the transducer to ablate tissue using short sonications. Conclusion A 1.75 dimensional array, that overcame the drawbacks associated with one-dimensional arrays, has been designed, built and successfully tested. Design issues, such as cable and ceramic capacitances, were taken into account when designing this array. The final prototype overcame also the problem of generating grating lobes at unwanted locations by tapering the array elements.
Saleh, Khaldon Y; Smith, Nadine Barrie
Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial
ObjectivesTo evaluate the efficacy and tolerability of the selective alpha1-adrenergic antagonist doxazosin and the 5-alpha-reductase inhibitor finasteride, alone and in combination, for the symptomatic treatment of benign prostatic hyperplasia.
Roger S Kirby; Claus Roehrborn; Peter Boyle; Georg Bartsch; Alain Jardin; Margaret M Cary; Michael Sweeney; Eric B Grossman
ObjectivesTo develop a prediction model, or nomogram, that would predict the probability that a man with benign prostatic hyperplasia would experience acute urinary retention (AUR) or require surgical intervention (SI) within 2 years, with or without dutasteride therapy.
Kevin M. Slawin; Michael W. Kattan; Claus G. Roehrborn; Timothy Wilson
The Combination of Avodart and Tamsulosin study was a 4-year, randomized, double-blind study of the efficacy and safety of dutasteride and tamsulosin, alone or in combination, in men with moderate-to-severe benign prostatic hyperplasia. In this post-hoc investigation, we analyzed primary and secondary end-points from the Combination of Avodart and Tamsulosin study in Asian (n = 325) and Caucasian men (n = 4259). The incidence of acute urinary retention or benign prostatic hyperplasia-related surgery did not differ significantly between treatment groups in the Asian subpopulation. In Caucasian men, the incidence of acute urinary retention/benign prostatic hyperplasia-related surgery was significantly lower in the combination therapy group compared with the tamsulosin monotherapy group (P < 0.001), but not compared with dutasteride monotherapy. Combination therapy significantly increased the time to benign prostatic hyperplasia clinical progression and resulted in improved International Prostate Symptom Score, maximum urinary flow rate, quality of life, and reduced prostate volume in Asian and Caucasian men who received combination therapy compared with tamsulosin monotherapy. Combination therapy also significantly improved (P < 0.05) time to benign prostatic hyperplasia clinical progression, International Prostate Symptom Score, maximum urinary flow rate and quality of life versus dutasteride in the Caucasian subpopulation. The adverse-event profile was comparable between subpopulations. In conclusion, Asian and Caucasian men respond similarly to these treatments, despite apparent racial differences in 5?-reductase activity. PMID:22774774
Chung, Byung-Ha; Lee, Seung Hwan; Roehrborn, Claus G; Siami, Paul F; Major-Walker, Kim; Wilson, Timothy H; Montorsi, Francesco
The number of trinucleotide repeats [CAG (coding for polyglutamine), GGC (coding for polyglycine)] in the first exon of the androgen receptor (AR) gene and prostate-specific antigen (PSA) gene androgen response element I A/G polymorphism are both related to prostate cancer prognosis. We investigated whether these genomic changes occur in the AR and PSA genes, which are usually found in individuals with prostate cancer, of Turkish patients and to find out their distribution in the population. We used PCR and PCR-RFLP assays for AR and PSA genes, respectively, to detect molecular changes in 44 prostate cancer patients. Our findings indicate that individuals with prostate cancer tend to have around 18 CAG trinucleotide repeats. We observed significant differences between 22 controls, 33 benign prostate hyperplasia (BPH) patients and 44 adenocarcinoma patients for long CAG repeats. However, we did not find any significant differences in GGC repeats between controls, BPH and adenocarcinoma patients (P = 0.408). We also did not observe significant differences in the PSA A/G polymorphism frequency between controls, BPH and adenocarcinoma patients (P = 0.483). In conclusion, CAG and GGC repeats in the AR and PSA gene polymorphisms may be associated with prostate cancer risk and BPH in the Turkish population. PMID:22653589
Alptekin, D; Izmirli, M; Bayazit, Y; Luleyap, H U; Yilmaz, M B; Soyupak, B; Erkoc, M A; Tansug, Z
Objectives.To determine the design and performance characteristics of two microwave antennae for use in thermal treatment of benign prostatic hyperplasia.Methods.Prostatron and Targis antennae were subjected to detailed physical examination and measurement. The heating patterns generated by these two types of antennae were characterized in detail using tissue-equivalent phantoms. Measurements of return loss as a function of frequency were conducted to
Thayne R. Larson; Michael L. Blute; Jeffrey L. Tri; Sidney V. Whitlock
Aim:To determine the effect of two different extracts of red maca in male rats.Methods:Prostatic hyperplasia was induced in male rats with testosterone enanthate (TE). The study comprised six groups: one control group (group 1), one group treated with TE (group 2), two groups treated with TE and aqueous extract of red maca (groups 3 and 4), one group treated with
Gustavo F. Gonzales; Vanessa Vasquez; Daniella Rodriguez; Carmen Maldonado; Juliet Mormontoy; Jimmy Portella; Monica Pajuelo; León Villegas; Manuel Gasco
Normal and hyperplastic prostatic tissues concentrate citrate within the epithelium; however, a unique biochemical property within prostate epithelial cells renders them dependent on glycolysis, rather than the citric acid cycle, for energy production. Lonidamine, an orally administered small molecule that inhibits glycolysis by the inactivation of hexokinase, may represent a unique and novel approach to the treatment of benign prostatic hyperplasia (BPH). Results of a phase II trial of lonidamine in BPH (described elsewhere in this supplement) are encouraging. Lonidamine is already used in the treatment of several cancers in other countries. Its target-specific nature renders it a safe compound for administration; in cancer therapy, patients have been treated with 40 times the daily dose used in the BPH trial, with negligible toxicity.
Brawer, Michael K
Multiple laser systems for the treatment of benign prostatic hyperplasia (BPH) have been introduced. Current laser systems\\u000a have limitations due to their laser physics. The RevoLix™ laser combines the advantages of the Holmium:YAG laser with the\\u000a comfort of a continuous wave (cw) laser beam. This study reports the preliminary results of vaporesection (simultaneous vaporization\\u000a and resection) of the prostate, using
Thorsten Bach; Thomas R. W. Herrmann; Roman Ganzer; Martin Burchardt; Andreas J. Gross
The treatment of benign prostatic hyperplasia can be accomplished by the use of different drugs including, doxazosin, an ?-1 adrenergic antagonist, and finasteride (FIN), a 5-? reductase inhibitor. Traditionally, treatments using these drugs have been administered as either a mono or combination therapy by the oral route. A transdermal delivery system optimized for doxazosin and FIN combination therapy would provide increased patient adherence and facilitate dose adjustment. Doxazosin base (DB) was prepared from doxazosin mesylate and characterized together with FIN, by X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). The permeation enhancers, azone and lauric acid, and the gelling agents, hydroxypropyl cellulose (HPC) and Poloxamer 407 (P407), were evaluated to determine their ability to promote in vitro permeation of drugs through the pig ear epidermis. Successful preparation of DB was confirmed by evaluating the XRD, DSC, and NMR patterns and in vitro studies revealed that 3% (w/w) azone was the best permeation enhancer. When P407 gel was compared with HPC gel, it showed reduced lag time and promoted higher permeation of both drugs. This may be because of the interactions of the former with the stratum corneum, which disorganizes the lipid structure and consequently promotes higher drug permeation. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4057-4064, 2013. PMID:23983168
Pupe, Carolina Gonçalves; Do Carmo, Flávia Almada; De Sousa, Valéria Pereira; Lopes, Marlene; Abrahim-Vieira, Bárbara; Ribeiro, António José; Veiga, Francisco; Rodrigues, Carlos Rangel; Padula, Cristina; Santi, Patrizia; Cabral, Lucio Mendes
Abstract Objectives: To identify the enablers and barriers affecting medication-taking behaviour in aging men with benign prostatic hyperplasia. Methods: A total of 40 patients attending the urology outpatient clinic in Melbourne in 2012 were screened. Patients who successfully met the inclusion criteria were interviewed using a structured interview schedule. Information regarding the patient's medication, demographic data and presence of co-morbidities was collected. Content analysis was compared with patient demographic and medical data, contributing to the analysis. Results: Problems with medication-taking were reported in 58% of patients. All patients without co-morbidities reported issues regarding their medications, whereas only 27% of patients with co-morbidities reported concerns regarding their medications. Statistical analysis revealed that patients without co-morbidities were significantly more likely (p?=?0.002) to have complaints with their medications compared to those with co-morbidities. Furthermore, patients with co-morbidities who required help of caregivers to assist with their medication-taking were significantly less likely (p?=?0.05) to have complaints with their medications compared to patients who self-managed. Conclusions: Older patients with caregivers who assisted managing their medication-taking had better adherence. Those receiving aid from their caregivers were significantly less likely to have complaints regarding their medications as opposed to those not requiring a caregiver. This highlights the importance of having support for medication-taking in patients with co-morbidities to assist with better adherence. PMID:23750816
Kusljic, Snezana; Manias, Elizabeth; Tran, Ben; Williams, Allison
The relationship between lower urinary tract symptoms secondary to BPH and ED has recently been the subject of significant research due to the prevalence of both conditions concomitantly existing in older men. Many large-scale studies have demonstrated an association between erectile dysfunction and lower urinary tract symptoms. Although the mechanisms underlying the relationship between LUTS and ED are not fully elucidated, several theories are currently proposed in literature: the nitric oxide/cGMP pathway, RhoA/Rho-kinase signaling, pelvic atherosclerosis associated with chronic hypoxia, and autonomic adrenergic hyperactivity. The mechanisms by which these pathways affect the bladder, prostate, pelvic vasculature and spinal cord are also the subject of current research. In this chapter, we examine the randomized, placebo-controlled trials that have evaluated the use of PDE-5Is in LUTS, as well as randomized, controlled trials (RCTs) researching combination PDE-5Is and alpha blockers. PMID:24136683
Lythgoe, Casey; McVary, Kevin T
Background Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including cancers of the prostate. Over the past several years, our group has been studying how mycoplasmas could possibly initiate and propagate cancers of the prostate. Specifically, Mycoplasma hyorhinis encoded protein p37 was found to promote invasion of prostate cancer cells and cause changes in growth, morphology and gene expression of these cells to a more aggressive phenotype. Moreover, we found that chronic exposure of benign human prostate cells to M. hyorhinis resulted in significant phenotypic and karyotypic changes that ultimately resulted in the malignant transformation of the benign cells. In this study, we set out to investigate another potential link between mycoplasma and human prostate cancer. Methods We report the incidence of men with prostate cancer and benign prostatic hyperplasia (BPH) being seropositive for M. hyorhinis. Antibodies to M. hyorhinis were surveyed by a novel indirect enzyme-linked immunosorbent assay (ELISA) in serum samples collected from men presenting to an outpatient Urology clinic for BPH (N = 105) or prostate cancer (N = 114) from 2006-2009. Results A seropositive rate of 36% in men with BPH and 52% in men with prostate cancer was reported, thus leading us to speculate a possible connection between M. hyorhinis exposure with prostate cancer. Conclusions These results further support a potential exacerbating role for mycoplasma in the development of prostate cancer.
In the first of these mini-reviews the selection of therapy for the maintenance of sexual function in patients with BPH is outlined, along with an explanation of how altered regulation of neurotransmitters, especially noradrenaline, may underlie the syndrome of LUTS and sexual dysfunction. Other mini-reviews outline the current status of robotic surgery to treat renal and adrenal disorders, and its
Purpose We conducted a safety and efficacy evaluation of intraprostatic injection of PRX302, a modified pore forming protein (proaerolysin) activated by prostate specific antigen, as a highly targeted, localized approach to treat lower urinary tract symptoms due to benign prostatic hyperplasia. Materials and Methods A total of 92 patients with I-PSS (International Prostate Symptom Score) 15 or greater, peak urine flow 12 ml or less per second and prostate volume 30 to 100 ml were randomized 2:1 to a single ultrasound guided intraprostatic injection of PRX302 vs vehicle (placebo) in this phase IIb double-blind study. Injection was 20% of prostate volume and 0.6 ?g PRX302 per gm prostate. Peak urine flow was determined by a blinded reviewer. Benign prostatic hyperplasia medications were prohibited. The primary data set of efficacy evaluable patients (73) was analyzed using last observation carried forward. Results PRX302 treatment resulted in an approximate 9-point reduction in I-PSS and 3 ml per second increase in peak urine flow that were statistically significant changes from baseline compared to vehicle. Efficacy was sustained for 12 months. Early withdrawal for other benign prostatic hyperplasia treatment was more common for patients in the vehicle group. Relative to vehicle, PRX302 apparent toxicity was mild, transient, and limited to local discomfort/pain and irritative urinary symptoms occurring in the first few days, with no effect on erectile function. Conclusions A single administration of PRX302 as a short, outpatient based procedure was well tolerated in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. PRX302 produced clinically meaningful and statistically significant improvement in patient subjective (I-PSS) and quantitative objective (peak urine flow) measures sustained for 12 months. The side effect profile is favorable with most effects attributed to the injection itself and not related to drug toxicity.
Elhilali, Mostafa M.; Pommerville, Peter; Yocum, Richard C.; Merchant, Rosemina; Roehrborn, Claus G.; Denmeade, Samuel R.
Present study depicted the role of polymorphisms in estrogen receptor-alpha gene in association with prostate cancer in north Indian population. The study was performed on 157 cases of prostate cancer, 170 cases of BPH, and 170 healthy Indian males diagnosed with prostate cancer and benign prostatic hyperplasia (BPH) and healthy males as controls. Determination of polymorphism in the ER-alpha gene was done by polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis with PvuII and XbaI enzymes. An association was observed between PvuII polymorphism of ER-alpha gene and that of prostate cancer. However, there was no such association with XbaI polymorphism in ER-alpha gene. PMID:19904497
Gupta, Lipsy; Thakur, Hitender; Sobti, Ranbir C; Seth, Amlesh; Singh, Sharwan K
Recent studies have suggested that vitamin D is an important determi- nant of prostate cancer risk and inherited polymorphisms in the 3*- untranslated region (3*UTR) of the vitamin D receptor (VDR) gene are associated with the risk and progression of prostate cancer. This study was conducted to explore the association of VDR gene polymorphisms with prostate cancer risk in Japanese
Tomonori Habuchi; Takehiro Suzuki; Ryusei Sasaki; Lizhong Wang; Kazunari Sato; Shigeru Satoh; Toshiya Akao; Norihiko Tsuchiya; Naotake Shimoda; Yasuhiko Wada; Akio Koizumi; Junichi Chihara; Osamu Ogawa; Tetsuro Kato
This study sought to evaluate the efficacy and safety of photoselective vaporisation (PVP) vs. transurethral resection of the prostate (TURP) for patients with benign prostatic hyperplasia (BPH). Eligible studies were identified from electronic databases (Cochrane Library, PubMed and EMBASE). The database search, quality assessment and data extraction were performed independently by two reviewers. Efficacy (primary outcomes: maximum urinary flow rate (Qmax), international prostate symptom score (IPSS), postvoid residual urine (PVR) and quality of life (QoL); secondary outcomes: operative time, hospital time and catheter removal time) and safety (complications, such as transfusion and capsular perforation) were explored by using Review Manager 5.0. Six randomized controlled trials (RCTs) and five case-controlled studies of 1398 patients met the inclusion criteria. A meta-analysis of the extractable data showed that there were no differences in IPSS, Qmax, QoL or PVR between PVP and TURP (mean difference (MD): prostate sizes <70 ml, Qmax at 24 months, MD=0.01, P=0.97; IPSS at 12 months, MD=0.18, P=0.64; QoL at 12 months, MD=?0.00, P=0.96; PVR at 12 months, MD=0.52, P=0.43; prostate sizes >70 ml, Qmax at 6 months, MD=?3.46, P=0.33; IPSS at 6 months, MD=3.11, P=0.36; PVR at 6 months, MD=25.50, P=0.39). PVP was associated with a shorter hospital time and catheter removal time than TURP, whereas PVP resulted in a longer operative time than TURP. For prostate sizes <70 ml, there were fewer transfusions, capsular perforations, incidences of TUR syndrome and clot retentions following PVP compared with TURP. These results indicate that PVP is as effective and safe as TURP for BPH at the mid-term patient follow-up, in particular for prostate sizes <70 ml. Due to the different energy settings available for green-light laser sources and the higher efficiency and performance of higher-quality lasers, large-sample, long-term RCTs are required to verify whether different energy settings affect outcomes.
Ding, Hui; Du, Wan; Lu, Ze-Ping; Zhai, Zhen-Xing; Wang, Han-Zhang; Wang, Zhi-Ping
Objectives. To study the efficacy and safety of dutasteride, a dual inhibitor of the 5-alpha-reductase isoenzymes types I and II.Methods. A total of 4325 men (2951 completed) with clinical benign prostatic hyperplasia, moderate to severe symptoms (American Urological Association-Symptom Index score of 12 points or greater), a peak flow rate of 15 mL\\/s or less, a prostate volume of 30
Claus G Roehrborn; Peter Boyle; J. Curtis Nickel; Klaus Hoefner; Gerald Andriole
Prostate cancer (PCA) is the most common type of cancer found in men of western countries and is the leading cancer death next to lung cancer and colorectal cancer. Prostate-specific antigen (PSA) test is an established diagnostic tool for PCA detection, but confirmation of diagnosis by histopathological evaluation of prostate needle biopsies is performed. To define protein expression pattern of
Ramesh Ummanni; Heike Junker; Uwe Zimmermann; Simone Venz; Steffen Teller; Jürgen Giebel; Christian Scharf; Christian Woenckhaus; Frank Dombrowski; Reinhard Walther
Background: The ?1–blocker doxazosin mesylate is an established efficacious and welltolerated treatment for benign prostatic hyperplasia (PBH). However, its clinical utility can be limited by the need for multiple titration steps, starting at an initial dose of 1 mg, increased up to 8 mg once daily, to achieve optimal therapeutic response. A new controlled–release gastrointestinal therapeutic system (GITS) formulation of
Morten Andersen; Christer Dahlstrand; Kjetil Høye
OBJECTIVES: To investigate whether 7-[2-[4-(2-chlorophenyl) piperazinyl] ethyl]-1,3-di-methylxanthine (KMUP-1) inhibits the effects of testosterone on the development of benign prostatic hyperplasia and sensitizes prostate contraction. METHODS: A benign prostatic hyperplasia animal model was established by subcutaneous injections of testosterone (3?mg/kg/day, s.c.) for 4 weeks in adult male Sprague-Dawley rats. Animals were divided into six groups: control, testosterone, testosterone with KMUP-1 (2.5, 5?mg/kg/day), sildenafil (5?mg/kg/day) or doxazosin (5?mg/kg/day). After 4 weeks, the animals were killed, and prostate tissues were prepared for isometric tension measurement and western blotting analysis. KMUP-1, Y27632, zaprinast, doxazosin or tamsulosin were used at various concentrations to determine the contractility sensitized by phenylephrine (10??mol/L). RESULTS: KMUP-1 inhibited testosterone-induced phosphorylation of extracellular signal-regulated phosphorylated protein kinase and mitogen-activated protein kinase kinase and Rho kinase-II activation. Sildenafil and doxazosin significantly decreased benign prostatic hyperplasia-induced mitogen-activated protein kinase kinase and Rho kinase-II activation. The decreased expressions of soluble guanylate cyclase??1 was reversed by KMUP-1, doxazosin and sildenafil. Soluble guanylate cyclase??1 and protein kinase?G were increased by KMUP-1, doxazosin, and sildenafil in the testosterone-treated benign prostatic hyperplasia group. Phosphodiesterase-5A was increased by testosterone and inhibited by KMUP-1 (5?mg/kg/day) or sildenafil (5?mg/kg/day). KMUP-1 inhibited phenylephrine-sensitized prostate contraction of rats treated with testosterone. CONCLUSIONS: Mitogen-activated protein kinase?1/extracellular regulated protein kinases kinase, soluble guanylate cyclase/cyclic guanosine monophosphate, protein kinase/protein kinase G and Rho kinase-II are related to prostate smooth muscle tone and proliferation induced by testosterone. KMUP-1 inhibits testosterone-induced prostate hyper-contractility and mitogen-activated protein kinase?1/extracellular regulated protein kinases kinase-phosphorylation, and it inactivates Rho kinase-II by cyclic guanosine monophosphate, protein kinase and ?1A-adenergic blockade. Thus, KMUP-1 might be a beneficial pharmacotherapy for benign prostatic hyperplasia. PMID:23692571
Liu, Chi-Ming; Fan, Ya-Chin; Lo, Yi-Ching; Wu, Bin-Nan; Yeh, Jwu-Lai; Chen, Ing-Jun
Transurethral vaporization of the prostate in saline (TURisV) is an innovative endoscopic surgical modality for the treatment of benign prostatic hyperplasia (BPH) that vaporizes prostate tissue using a uniquely designed mushroom electrode. TURisV promises instant hemostatic tissue ablation under saline irrigation and offers clinical advantages for endoscopic BPH operations. From July 2008 to February 2009, TURisV was performed in 17 cases with clinically significant BPH. Median operation time was 127.0 min and median volume of vaporized prostate tissue was 41.1 g. Median International Prostate Symptom Score improved from 20 to 4 after 12 months. Median maximum flow rate increased from 5.3 mL/s to 13.8 mL/s after 12 months. Postoperative median residual urine improved from 48.0 mL to 7.0 mL after 12 months. No changes in hemoglobin or electrolyte levels were seen postoperatively. Our results suggest that TURisV is a safe and efficacious treatment for BPH. PMID:22776338
Isotani, S; Muto, S; Yu, J; Nagae, M; China, T; Koseki, T; Kumamoto, T; Tokiwa, S; Yoshii, T; Saito, K; Yamaguchi, R; Ide, H; Horie, S
Transurethral resection of the prostate (TURP) has long been considered the gold standard therapy for benign prostatic hyperplasia (BPH). The problems associated with the TURP, which have been extensively described, include significant bleeding, TUR syndrome, incontinence, stricture, bladder neck contracture, and sexual dysfunction. The desire for simpler, less morbid alternative therapies to TURP has led to an eruption of research and development in the last decade. This is fueled by the continued research for more economical alternatives in our current high cost health care system.
Ulchaker, James C.; Ng, Christopher S.; Palone, David; Angie, Michelle; Kursh, Elroy D.
With the emergence of minimally invasive therapies for the management of symptoms of benign prostatic hyperplasia (BPH), as well as the reality of a changing medical economic environment, there is a need for a reliable local anesthesia protocol. The protocol described here for prostate anesthetic block is a safe, economical, and effective way to perform interstitial laser coagulation and other minor endoscopic urologic procedures in the office setting. Most patients experience little discomfort and recover quickly, with prompt return to normal activities. Urologists should be aware of and comfortable with these techniques.
Kedia, Kalish R
In order to evaluate the biochemical modifications induced by hormonal treatments on human prostatic tissue, the intracellular distribution of tissue DHT and AR were investigated in BPH patients untreated and treated (25-30 days before surgery) with the association of cyproterone acetate (CPA), 100 mg p.o./day plus tamoxifen (TAM), 100 mg p.o./day, or with flutamide (FLU) alone, 750 mg p.o./day. Dextran-coated charcoal and exchange assay in the presence of sodium molybdates (0.2 M) were used for AR determination, employing methyltrienolone as radioligand in the presence of triamcinolone acetonide. Endogenous DHT was measured by RIA, after ether extraction and purification on celite microcolumns. The treatment with CPA plus TAM led to a detection of cytosol AR (ARc) in 50% of the specimens, while nuclear AR (ARn) were never measurable. The FLU treatment did not modify the incidence of ARc, while ARn was not detectable. The cytosolic and nuclear compartmentalization of DHT was scarcely affected by the combined CPA plus TAM treatment, while FLU treatment induced a prevalent cytosolic localization of DHT (DHTc = 283.2 +/- 24.6 S.E. and DHTn = 1138.4 +/- 98.7 S.E. pg/mg DNA in untreated patients; DHTc = 350.4 +/- 97.7 S.E. and DHTn = 589.7 +/- 154.4 S.E. pg/mg DNA in CPA plus TAM treated patients; DHTc = 1101.7 +/- 165.7 S.E. and DHTn = 733.0 +/- 93.9 S.E. pg/mg DNA in FLU treated patients). Both medical treatments, therefore, were able to reduce prostatic growth on account of the reduced value of nuclear DHT content. PMID:2455099
Petrangeli, E; Sciarra, F; Di Silverio, F; Toscano, V; Lubrano, C; Conti, C; Concolino, G
A 62-year-old male presented with symptoms of urinary obstruction and elevated serum prostate-specific antigen level of 3.61 ng/mL. Prostate needle biopsies showed benign prostatic tissue with a focus of crowded glands with minimal cytological atypia, fairly well-circumscribed with infiltrative appearance of glands at the edges. This focus had both small and larger glands with similar histological features. This focus was strongly positive for alpha-methylacyl-coenzyme A-racemase (AMACR), but showed scattered patchy staining with basal cell markers (p63 and CK903/34?E12). Hence, the final histologic diagnosis was benign prostatic tissue with a focus of florid adenosis. Two subsequent follow-up prostate needle biopsies performed six and 12 months later both showed benign prostatic tissue with atrophic changes. This case highlights the utility of these three immunostains (AMACR, p63 and CK903/34?E12) in the accurate diagnosis of adenosis of the prostate on needle biopsy, and avoiding its misinterpretation as prostate adenocarcinoma.
Armah, Henry B; Parwani, Anil V
We evaluate the feasibility of proton magnetic resonance spectroscopy ((1)H MRS) using a spine coil receiver (body coil) in the diagnosis of carcinoma prostate. Seventeen patients with biopsy-proven prostate carcinoma, five patients of benign prostatic hyperplasia (BPH) and five healthy young volunteers underwent (1)H MRS investigation. MRS was performed at 1.5 Tesla using a spine receiver coil for signal reception. In vivo citrate levels are reported as a ratio of citrate peak area to the sum of the areas of choline and creatine peak. MRS spectrum with good sensitivity and signal to noise (S/N) ratio was obtained in all 27 subjects. The citrate to creatine plus choline ratio was 0.31+/-0.25 in patients with cancer, 1.43+/-0.58 in BPH and 2.16+/-0.56 in controls. The difference in ratios between cancer and BPH and cancer and control was statistically significant ( p<0.01). Within the cancer group, there was a statistically significant decline in levels with higher-grade malignancy ( p<0.05). There were no complications of the procedure. There is a statistically significant decline in the ratio of citrate to choline plus creatine in the regions of cancer prostate when compared with BPH or normal control. The study demonstrates that MRS data can be reliably acquired using a spine coil receiver. MRS may also play a role in differentiating well-differentiated tumors from the anaplastic variety. PMID:14534764
Kumar, Rajeev; Kumar, Mahesh; Jagannathan, N R; Gupta, Narmada P; Hemal, Ashok K
Purpose The aim of this study was to investigate the expression pattern of calcium-binding proteins S100A2 and S100A4. We also sought to determine the prognostic value of these markers for patients with prostate adenocarcinoma. Materials and Methods Immunohistochemical staining was performed to detect S100A2 and S100A4 expression in 26 tissue samples obtained during transurethral resection from patients with benign prostatic hyperplasia (BPH) and in 67 tissue samples obtained during prostate biopsy and radical prostatectomy from patients with prostate carcinoma. The immunoreactivity of these proteins was stratified on a scale of 0 to 3 and was correlated with the pathologic features of prostate adenocarcinoma. Results High expression of S100A2 was observed in the tissue of patients with BPH, whereas low or no expression was observed in prostate cancer (CaP) cells. The protein level of S100A4 was significantly higher in CaP than in BPH cells. The higher level of S100A4 observed in CaP tissue correlated with increasing tumor grade. Conclusions Decreased expression of S100A2 and increased expression of S100A4 may be important in the progression of CaP. This finding could aid in identifying aggressive CaP. The simultaneous analysis of S100A2 and S100A4 expression in prostate tissues may be a useful prognostic marker for CaP.
Kwon, Yong-Wook; Chang, In Ho; Kim, Kyung Do; Kim, Young Sun; Myung, Soon-Chul; Kim, Mi-Kyung
Objectives. A pooled analysis was conducted in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia to examine the relationship between the postvoid residual urine (PVR) volume and various clinical characteristics and to assess the effect of alfuzosin, a clinically uroselective alpha1-blocker, on PVR volume and any other associated outcome.Methods. Nine hundred fifty-three patients, 42 to 89 years
S. Alan McNeill; Timothy B Hargreave; Christine Geffriaud-Ricouard; Jean-Philippe Santoni; Claus G Roehrborn
Parathyroid hormone-related protein (PTHrP) has been shown to be the primary factor responsible for humoral hypercalcemia of malignancy. Recently PTHrP has been shown to be an early-response gene that may be involved in cellular proliferation or differentiation. In addition, PTHrP has been implicated in the pathogenesis of bone metastases. Bone metastases are a significant complication in patients with prostate cancer.
Farrokh Asadi; Mohammad Farraj; Rohollah Sharifi; Sadegh Malakouti; Salah Antar; Subhash Kukreja
What is it that the clinician "feels" during a digital rectal examination? To answer this question, it is necessary to measure the elastic properties of the prostate and verify the stiffness values with histological examination. Therefore, we devised an Elasticity Mapping System to evaluate the elastic properties of various histopathological grades of prostate cancer in relation to benign prostatic hyperplasia (BPH) and normal tissue. The system consists of a micro tactile sensor, a three-axis (XYZ) with one (fine Z) micromanipulation stage, a stereoscope camera and a measurement chamber. Using this methodology we mapped the elasticity of human prostate cancer (CaP) and it was obviously observed that the node was significantly harder than surrounding normal tissues and had some textures. PMID:18003332
Murayama, Yoshinobu; Omata, Sadao; Yajima, Toshikuni; Peng, Qiyu; Shishido, Keiichi; Peehl, Donna M; Constantinou, Christos E
A systems-level mathematical model is presented that describes the effects of inhibiting the enzyme 5?-reductase (5aR) on the ventral prostate of the adult male rat under chronic administration of the 5aR inhibitor, finasteride. 5aR is essential for androgen regulation in males, both in normal conditions and disease states. The hormone kinetics and downstream effects on reproductive organs associated with perturbing androgen regulation are complex and not necessarily intuitive. Inhibition of 5aR decreases the metabolism of testosterone (T) to the potent androgen 5?-dihydrotestosterone (DHT). This results in decreased cell proliferation, fluid production and 5aR expression as well as increased apoptosis in the ventral prostate. These regulatory changes collectively result in decreased prostate size and function, which can be beneficial to men suffering from benign prostatic hyperplasia (BPH) and could play a role in prostate cancer. There are two distinct isoforms of 5aR in male humans and rats, and thus developing a 5aR inhibitor is a challenging pursuit. Several inhibitors are on the market for treatment of BPH, including finasteride and dutasteride. In this effort, comparisons of simulated vs. experimental T and DHT levels and prostate size are depicted, demonstrating the model accurately described an approximate 77% decrease in prostate size and nearly complete depletion of prostatic DHT following 21 days of daily finasteride dosing in rats. This implies T alone is not capable of maintaining a normal prostate size. Further model analysis suggests the possibility of alternative dosing strategies resulting in similar or greater effects on prostate size, due to complex kinetics between T, DHT and gene occupancy. With appropriate scaling and parameterization for humans, this model provides a multiscale modeling platform for drug discovery teams to test and generate hypotheses about drugging strategies for indications like BPH and prostate cancer, such as compound binding properties, dosing regimens, and target validation.
Zager, Michael G.; Barton, Hugh A.
BPH remains one of the most common disease that the urologist has to manage. The last decade brought numerous new techniques, aiming to improve the minimally invasive approach to BPH, but none had, for the moment, changed the place of TURP as the gold standard treatment for medium sized prostates. Based on a large personal experience, the authors present a study in which TURP is used for prostates over 80ml, the cutoff point set by the guidelines of the European Association of Urology. The rationale for this study is that many situations require minimally invasive treatment, based on the express request of the patient, other conditions that makes open surgery very difficult or impossible, or the need for a quick discharge in an overcrowded service. The aim of the study was to prove that TURP is safe and effective even in larger prostates. The technique used is basically the classic one, with minor tactical alterations in some cases. Some cases required a two-stage approach, but offered good functional results after the first stage. The results proved that, with a good technique, a skilled urologist might achieve the same results by using TURP or open surgery for large sized prostates.
Georgescu, D; Arabagiu, I; Cauni, V; Moldoveanu, C; Geavlete, P
Prostate cancer is the leading cancer type diagnosed in American men and is the second leading cancer diagnosed in men worldwide. Although studies have been conducted to investigate the association between prostate cancer and exposure to pesticides and/or farming, the results have been inconsistent. We performed a meta-analysis to summarize the association of farming and prostate cancer. The PubMed database was searched to identify all published case-control studies that evaluated farming as an occupational exposure by questionnaire or interview and prostate cancer. Ten published and two unpublished studies were included in this analysis, yielding 3,978 cases and 7,393 controls. Prostate cancer cases were almost four times more likely to be farmers compared with controls with benign prostate hyperplasia (BPH; meta odds ratio [OR], crude = 3.83, 95% confidence interval [CI] = 1.96-7.48, Q-test p value = .352; two studies); similar results were obtained when non-BPH controls were considered, but with moderate heterogeneity between studies (meta OR crude = 1.38, 95% CI = 1.16-1.64, Q-test p value = .216, I (2) = 31% [95% CI = 0-73]; five studies). Reported pesticide exposure was inversely associated with prostate cancer (meta OR crude = 0.68, 95% CI = 0.49-0.96, Q-test p value = .331; four studies), whereas no association with exposure to fertilizers was observed. Our findings confirm that farming is a risk factor for prostate cancer, but this increased risk may not be due to exposure to pesticides. PMID:22948300
Ragin, Camille; Davis-Reyes, Brionna; Tadesse, Helina; Daniels, Dennis; Bunker, Clareann H; Jackson, Maria; Ferguson, Trevor S; Patrick, Alan L; Tulloch-Reid, Marshall K; Taioli, Emanuela
Purpose Metabolic syndrome (MS) plays a potential role in the etiology of benign prostatic hyperplasia (BPH). Recent studies have reported on an association between MS and BPH. However, there has been no consensus on recent results. This study was conducted to evaluate the associations among prostate-specific antigen (PSA), prostate volume (PV), and metabolic components in men who visited our health promotion center. Materials and Methods During the period from January 2005 to December 2010, 521 consecutive men (age range, 40 to 70 years) who underwent transrectal ultrasonography were enrolled in this retrospective study. The health screening program includes blood pressure, body measurements (height, weight, waist circumference, body mass index), biochemical analysis (serum glucose, total cholesterol, triglycerides, high-density and low-density lipoprotein cholesterol, fasting plasma glucose, tumor markers), stool and urine analysis, and a detailed clinical examination. Results The serum PSA level and PV were significantly higher in patients with MS than in patients without MS, retrospectively (p<0.001, p<0.001). Patients with more than one metabolic component were significantly more likely to have a larger PV and higher serum PSA level. The serum PSA level and PV were increased in a similar manner with the increasing sum of MS components (p<0.0001, p<0.0001). Conclusions The MS components were associated with larger PV and higher serum PSA level. Therefore, each MS component could be an important factor in BPH development and management.
Byun, Hyun Keun; Sung, Yun Hsien; Kim, Won; Jung, Jae Hung; Song, Jae Mann
The aim of this study was to systematically review the evidence on the efficacy and safety of silodosin treatments on lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) from randomized controlled trials. We searched PubMed (1966-December 2011), Embase (1974-December 2011) and the Cochrane Library Database (2011, Issue 12). The assessed outcome measures were the change from baseline for the International Prostate Symptom Score (IPSS), quality of life (QoL) score, peak urine maximum flow rate (Q(max)), QoL related to urinary symptoms and adverse effects. Two authors independently assessed the study quality and extracted data. All data were analysed using RevMan 5.1. The meta-analysis included four randomized controlled trials with a total of 2504 patients. The study durations were each 12 weeks. At the follow-up end points, the pooled results showed that the change from baseline for the silodosin group was significantly higher than the placebo group for the IPSS, QoL score and Q(max)(mean difference (MD)=-2.78, P<0.00001; MD=-0.42, P=0.004; MD=1.17, P<0.00001,respectively) and patients felt more satisfied with QoL related to urinary symptoms in the silodosin group than the placebo group. Ejaculation disorder was the most commonly reported adverse effect. The pooled results also showed that the silodosin group was superior to the 0.2 mg tamsulosin group with respect to the IPSS and QoL score (IPSS: MD=-1.14, P=0.02; QoL score: MD=-0.26, P=0.02) and inferior to the 0.2 mg tamsulosin group with respect to Q(max) (MD=-0.85, P=0.01). In contrast, there was no significant difference in the incidence of ejaculation disorder and dizziness between the silodosin and 0.2 mg tamsulosin groups. The current meta-analysis suggested that silodosin is an effective therapy for LUTS in men with BPH and is not inferior to 0.2 mg tamsulosin. PMID:23223034
Ding, Hui; Du, Wan; Hou, Zi-Zhen; Wang, Han-Zhang; Wang, Zhi-Ping
Prostate cancer represents a heterogeneous disease with varying degrees of aggressiveness, patterns of metastasis, and response to therapy. It arises from a complex etiology that involves both exogenous (diet, environment, etc.) and endogenous (hormonal and genetic) factors. The present study was performed to explore the role of various genotypes involved in steroid metabolism and synthesis in the causation of prostate cancer. Genetic polymorphism of the ER, CYP17, SRD5A2 (TA repeats), and PSA genes were analyzed in 157 cases of prostate cancer and 340 controls [170 healthy males and 170 patients of benign prostate hyperplasia (BPH)]. Mutant genotypes of ER and CYP17 showed 2- and 3- and 3.5-fold increased risk of prostate cancer, respectively, as compared to BPH and healthy controls. Interaction of mutant (homozygous and heterozygous) alleles of CYP17 with TA (0/0) led to a twofold increased risk of prostate cancer. Risk was more than twofold with the combination of mutant alleles of ER and CYP17. The PSA gene polymorphism did not show any increased risk of prostate cancer. This indicates the role of mutant allele of ER and CYP17 in the development and progression of prostate cancer and rules out any increased risk with PSA polymorphism in the north Indian population. PMID:18722876
Sobti, R C; Gupta, L; Singh, S K; Seth, A; Kaur, P; Thakur, H
We report on the new technique of interstitial laser coagulation of the prostate (ILCP) in the treatment of benign prostatic hyperplasia (BPH). Basic experiments by use of a Nd:YAG laser in combination with a newly designed fiber tip homogeneously distributing the laser irradiation have been performed in potato, muscle, liver, and surgically removed human BPH-tissue to determine the volume of coagulation. The coagulation zone surrounding the probe was well defined and homogeneous. The size was dependent on laser power and irradiation time. Carbonization was never present except in darker tissues irradiated with high energy. Volume and time resolved measurements correlated well with the size of coagulation. 10 W and 5 minutes, for example, resulted in a coagulation zone of 17 X 15 mm. Comparable results have been seen in in-vivo experiments in surgically exposed canine prostates. Specimen for macroscopic and microscopic examination were taken immediately after treatment and after 5 and 35 days. The well demarked coagulation necrosis of the early stage resulted in cystic degeneration and fibrosis in the later stages. This was combined with shrinkage and reduction in volume. The urothelium of the urethra, the external sphincter and the rectum showed no damage. Until now, 15 patients suffering from obstructive symptoms due to BPH have been treated with interstitial laser coagulation. The probes were inserted from the perineum into the center of each lateral lobe of the prostate by transrectal ultrasound guidance, while the median lobe was treated by urethroscopic guidance, while the median lobe was treated by urethroscopic control. Dependent on the size of the prostate irradiation, time was 5 to 10 minutes per lobe at a power setting of 5 to 10 W.
Muschter, Rolf; Hofstetter, Alfons G.; Hessel, Stefan F.; Keiditsch, Ernst; Rothenberger, Karl-Heinz; Schneede, Peter; Frank, Klaus H.
One of the most important diagnostic tools used to detect prostate cancer is prostate-specific antigen (PSA), yet increased PSA alone does not reflect the presence of prostate cancer. Other pathological prostatic conditions such as prostatitis and benign prostatic hyperplasia (BPH) may also increase the level of PSA. However, unlike in other prostate diseases, PSA has a key role in the diagnosis and management of prostate cancer. The incidence of prostate cancer varies from country to country, with the highest incidence being found in the Western world and the lowest in Asian countries. Owing to the low incidence of prostate cancer, there could be different views regarding the use of PSA in Asian countries, especially for the early detection/screening of prostate cancer. The purpose of this article is to review the use and value of PSA in the diagnosis of prostate diseases (especially prostate cancer) in Asian countries/populations. A literature search was performed in ‘MEDLINE’ (PubMed) and Google Scholar using main keywords such as ‘PSA’, ‘PSA usage’, ‘PSA sensitivity and specificity’, ‘Asia’, and various countries in Asia. Articles that provide population/community-based PSA data, together with the characteristics, distribution, and indications for PSA testing in the respective countries, were selected. Eleven papers were finally selected for inclusion in this review. Five studies found that PSA, by its 95th percentile value, have an age-referenced tendency in Asian males, similarly to the West. The predictive values of PSA in detecting prostate cancer are also quite similar to those in Western countries. With the exponential growth of the aging population in the world, especially in Asia, the incidence of prostate cancer will follow this upward trend. Therefore, PSA testing for screening or diagnostic purposes would increase with time in Asia.
Mochtar, Chaidir Arif; Andika, R. Siddhi
To determine whether the inhibition of estrogen-related effect in the prostate would be of value in the management of benign prostate hyperplasia (BPH), we examined the effect of TZA-2209, a new steroidal aromatase inhibitor, on the prostate in three of six castrated beagles that received 75 mg/week androstenedione. The three other animals served as controls. Sequential measurements of prostate volume by transrectal ultrasonography showed that the volume in TZA-treated dogs was significantly decreased compared with that in the controls. Prostatic aromatase activity was suppressed by TZA administration. Histopathologically, the stromal component was increased and glands were atrophied by androstenedione treatment. TZA administration increased the volume of the glands. Immunohistochemical detection of estramustine-binding protein showed more positive staining of the protein in the glands that were increased in volume by TZA administration. We concluded that the aromatase inhibitor effectively antagonized the estrogen-related stromal changes, however, this action was accompanied by stimulation of the glandular component due to the accumulation of androgens, the substrate of the aromatase. In the light of these findings, we suggest the simultaneous treatment for the androgen-glandular component route in the prostate is necessary for the effective management of BPH. PMID:8610061
Suzuki, K; Ito, K; Tamura, Y; Suzuki, T; Honma, S; Yamanaka, H
Prostate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5' end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ± 2.65, in controls 22.28 ± 2.86 (p = 0.009) and in BPH patients 22.1 ± 2.52 (p = 0.038). Short CAG repeats (<19) were found in 21.64% of PC patients vs. 9.43% in BPH patients (p = 0.0154). We also found an association of low Gleason score (<7) with short CAG repeat (<19) in PC patients (p = 0.0306), and no association between the age at diagnosis of PC and BPH and CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men. PMID:24052720
Madjunkova, S; Eftimov, A; Georgiev, V; Petrovski, D; Dimovski, Aj; Plaseska-Karanfilska, D
Prostate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5? end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ± 2.65, in controls 22.28 ± 2.86 (p = 0.009) and in BPH patients 22.1 ± 2.52 (p = 0.038). Short CAG repeats (<19) were found in 21.64% of PC patients vs. 9.43% in BPH patients (p = 0.0154). We also found an association of low Gleason score (<7) with short CAG repeat (<19) in PC patients (p = 0.0306), and no association between the age at diagnosis of PC and BPH and CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men.
Madjunkova, S; Eftimov, A; Georgiev, V; Petrovski, D; Dimovski, AJ; Plaseska-Karanfilska, D
Deregulation of epithelial-stromal interactions is considered to play a critical role in the initiation and promotion of benign prostatic hyperplasia (BPH) and prostate carcinoma (PCa). Expression of tenascin-C (TN-C), an extracellular matrix (ECM) glycoprotein, is reportedly higher in BPH and PCa as compared with normal prostate. Remodeling of the ECM alters the homeostatic balance between epithelium and stroma, resulting in physiological changes in cellular functions. To investigate the role of TN-C in prostatic development and differentiation, we evaluated the morphological phenotype of TN-C knockout (KO) mouse prostate (ventral: VP, dorsolateral: DLP, and anterior: AP) and examined tissue recombinants composed of adult mouse DLP epithelium and fetal TN-C KO urogenital sinus mesenchyme (UGM). Histological analysis showed epithelial cell clusters protruding into the ductal lumens in TN-C KO AP and DLP. Interestingly, binucleated cells appeared in epithelium of TN-C KO DLP at 8 weeks. Simultaneously, androgen receptor (AR)-positive cells were decreased in TN-C KO epithelia. Similar to the TN-C KO phenotype, protruded epithelial clusters, binucleated cells, and AR-negative nuclei were induced in DLP epithelium by recombining with TN-C KO UGM. Our results suggest that stromal TN-C might be involved in maintaining epithelial cytodifferentiation, morphogenesis, and androgen receptor expression of normal prostate glands in adult mice. PMID:18950615
Ishii, Kenichiro; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Sugimura, Yoshiki
The glutathione S-transferase (GST) family of enzymes is known to play a pivotal role in phase II of biotransformation of xenobiotics, environmental carcinogens and pharmacological drugs. The objective of the present study was to investigate the role of GSTM1 and GSTT1 null genotypes as risk factors for chronic obstructive pulmonary disease (COPD) and prostate cancer. The subjects appraised were 200 COPD cases, 150 prostate cancer cases, 150 benign prostatic hyperplasia (BPH) cases, 200 age matched controls for COPD and 172 age matched controls for prostate cancer. GSTM1 and GSTT1 null genotype was found to confer 2.5 (OR 2.45; 95% CI 1.56-3.82; P value = 0.00008) and 2.4-fold (OR 2.39; 95% CI 1.36-4.20; P value = 0.002) significant higher risk for prostate cancer. Smoking imparted a 2.2-fold significant risk of prostate cancer cases (OR 2.23; 95% CI 1.36-3.65 P value = 0.001) and twofold risk in BPH (OR 2.09; 95% CI 1.26-3.46; P value = 0.005). In case of COPD only null genotype of GSTT1 has shown 2.1-fold (OR 2.11; 95% CI 1.22-3.62; P value = 0.007) significant increased risk. PMID:20842440
Thakur, Hitender; Gupta, Lipsy; Sobti, Ranbir C; Janmeja, Ashok K; Seth, Amlesh; Singh, Sharwan K
Many men with benign prostatic hyperplasia (BPH) forego therapy because they are dissatisfied with current treatment options. While surgical resection and ablation using many different forms of energy remain the reference standard for BPH treatment, many men seek a less invasive technique that will improve symptoms but not risk the complications associated with tissue removal. The Prostatic Urethral Lift opens the prostatic urethra with UroLift (NeoTract Inc., Pleasanton, CA, USA) permanent implants that are delivered under cystoscopic visualization. The implants literally "hold open" the lateral prostatic lobes creating a passage through the obstructed prostatic urethra. Voiding and symptoms are significantly improved without the morbidity or possible complications following prostate resection. The entire procedure can be readily performed using local anesthesia. As with all new implant procedures, the technique has evolved with experience. The objective of this article is to describe the most current technique for the delivery of the UroLift implant in order to achieve maximal impact on symptom relief. PMID:22512970
Barkin, Jack; Giddens, Jonathan; Incze, Peter; Casey, Richard; Richardson, Stephen; Gange, Steven
Objective The molecular mechanism of prostate cancer is poorly understood. The aim of the study was to investigate the prevalence and prognostic value of promoter hypermethylation of retinoic acid receptor beta (RARB) and p16 among benign prostatic hyperplasia (BPH) and prostate cancer patients. Methods In this case-control study, 63 patients were included in three groups; 21 with BPH as the control group, 21 with prostate cancer and good prognostic factors (based on prostate-specific antigen, Gleason score and stage) as good prognosis group, and 21 with prostate cancer and poor prognostic features as poor prognosis group. The prostate biopsy specimen of each individual was examined for hypermethylation of RARB and p16 promoters by methylation specific PCR (MSPCR). Results Seven (33.3%) patients with good prognosis and 15 (71.4%) patients with poor prognosis were positive for RARB methylation, which were significantly higher than controls (P<0.0001). p16 promoter methylation was shown in 19.0% and 47.6% patients with good and poor prognosis, respectively. The RARB and p16 promoter methylation in the poor prognosis group was significantly higher than that in the good prognosis group (P =0.02 for RARB and P<0.0001 for p16). Conclusion Hypermethylation of RARB and p16 promoters may predict prognosis in prostate cancer.
Ameri, Ahmad; Alidoosti, Asdollah; Hosseini, Seyed Yousef; Parvin, Mohammad; Emranpour, Mohammad Hasan; Taslimi, Farnaz; Salehi, Eisa; Fadavip, Pedram
Ways are explored in which public library children's librarians can help sighted children increase their understanding of persons with visual impairment and their skills in communicating with them. Interviews were conducted with six children's librarians and six BPH subregional librarians, and searches were made in the public library catalogs and the Regional BPH Library fiche catalog for selected titles. Three
Florence E. DeHart; Karen Matthews
Lectins, proteins which selectively recognize carbohydrates, have been used in histochemistry for the evaluation of changes in glycosylation in processes of cellular differentiation and/or dedifferentiation. Cratylia mollis seed lectins (Cramoll 1,4 and Cramoll 3), conjugated to horseradish peroxidase, were used as histochemical probes in human prostate tissues: normal (NP), hyperplasia (BPH), and prostate carcinoma (PCa). The staining pattern of Con-A and Cramoll 1,4 in BPH was more intense than in NP. These lectins also showed staining differences between BPH and PCa; the latter showing decreased staining intensity with an increased degree of malignancy. PNA and Cramoll 3 stained epithelial cells similarly in all diagnoses although they did present intense staining of PCa glands lumen. Corpora amylacea were not differentially recognized by any of the lectins. Cramoll 1,4 and Cramoll 3 seed lectins present themselves as candidates for histochemical probes for prostate pathologies when compared to commercial lectins such as Con-A and PNA. PMID:20617135
de Lima, Amanda L R; Cavalcanti, Carmelita C B; Silva, Mariana C C; Paiva, Patrícia M G; Coelho, Luana C B B; Beltrão, Eduardo I C; dos S Correia, Maria T
One of the questions raised regarding the use of transrectal thermal therapy in the treatment of benign prostatic hyperplasia (BPH) is whether there is a uniform and safe temperature distribution within the prostate. Our study represents the first attempt in humans to map the interstitial thermal distribution in the prostate during transrectal thermal therapy. With the patient under local anesthesia and under ultrasound guidance, a transperineal 3-point thermocouple was placed into various areas of the prostate in 15 patients. Prostatic-urethral thermocouple distance ranged from 1 to 3 cm. A urethral catheter containing a 5-point linear array thermocouple was placed and the balloon was inflated so that the proximal point was at the bladder neck and the remaining points were at 1 cm. intervals along the prostatic urethra. Power (25 watts) was delivered via the Primus (Technomatix) transrectal microwave applicator with simultaneous cooling of the rectal mucosa (between 12 and 14C). Treatment was delivered for 60 minutes and temperatures were recorded. In the prostatic substance a maximal temperature of 45C was observed during the heat-up phase and this decreased as the vasoactive response occurred. Temperature along the prostatic urethra varied between 40 and 43C and never exceeded 44C. A similar distribution of temperature was registered in the thermocouple points in the prostatic substance. The anticipated thermal dose of 41.5 +/- 1C for 60 minutes was achieved in the prostatic substance as measured by the sensors in the prostatic urethra and interstitial sensors. The results suggest that transrectal thermal therapy delivers a uniform and safe distribution of heat in the prostatic substance and urethra. Clinical trials are currently underway to ascertain the efficacy of transrectal thermal therapy in the management of BPH. PMID:1375661
Kaplan, S A; Shabsigh, R; Soldo, K A; Olsson, C A
Evaluation and validation of the Core Lower Urinary Tract Symptom Score as an outcome assessment tool for the treatment of benign prostatic hyperplasia: Effects of the ?1-adrenoreceptor antagonist silodosin.
We investigated the Core Lower Urinary Tract Symptom Score as an outcome assessment tool for the treatment of lower urinary tract symptoms using silodosin. In addition, the ability of the Core Lower Urinary Tract Symptom Score to detect overactive bladder in male patients with lower urinary tract symptoms was examined. The present study included 241 males with benign prostatic hyperplasia treated at 31 medical facilities between June 2009 and December 2010. All patients were given silodosin, and the effects of silodosin intake were measured using four questionnaires: the Core Lower Urinary Tract Symptom Score, International Prostate Symptom Score, Overactive Bladder Symptom Score and Quality-of-Life index. The efficacy of silodosin for treating lower urinary tract symptoms was validated according to the total scores of all four questionnaires weighted equally (P?0.05). Spearman's ? among the Core Lower Urinary Tract Symptom Score, International Prostate Symptom Score and Overactive Bladder Symptom Score showed a mild-high correlation. However, the correlation between the baseline values of the Core Lower Urinary Tract Symptom Score and Quality-of-Life index was low in the groups with benign prostatic hyperplasia (??=?0.314) and benign prostatic hyperplasia/overactive bladder (??=?0.244). Our findings showed the Core Lower Urinary Tract Symptom Score, both its total score and each subscore, is able to show the efficacy of silodosin, similar to other questionnaires. The Core Lower Urinary Tract Symptom Score is also useful for identifying overactive bladder symptoms in patients with benign prostatic hyperplasia. As the Core Lower Urinary Tract Symptom Score does not correlate well with the Quality-of-Life index, these two questionnaires might be better used in combination to assess treatment outcomes. PMID:23662900
Ito, Hiroki; Sano, Futoshi; Ogawa, Takehiko; Yao, Masahiro
The identification of biomarkers capable of providing a reliable molecular diagnostic test for prostate cancer (PCa) is highly desirable clinically. We describe here 4 biomarkers, UDP-N-Acetyl-alpha-D-galactosamine transferase (GalNAc-T3; not previously associated with PCa), PSMA, Hepsin and DD3/PCA3, which, in combination, distinguish prostate cancer from benign prostate hyperplasia (BPH). GalNAc-T3 was identified as overexpressed in PCa tissues by microarray analysis, confirmed by quantitative real-time PCR and shown immunohistochemically to be localised to prostate epithelial cells with higher expression in malignant cells. Real-time quantitative PCR analysis across 21 PCa and 34 BPH tissues showed 4.6-fold overexpression of GalNAc-T3 (p = 0.005). The noncoding mRNA (DD3/PCA3) was overexpressed 140-fold (p = 0.007) in the cancer samples compared to BPH tissues. Hepsin was overexpressed 21-fold (p = 0.049, whereas the overexpression for PSMA was 66-fold (p = 0.047). When the gene expression data for these 4 biomarkers was combined in a logistic regression model, a predictive index was obtained that distinguished 100% of the PCa samples from all of the BPH samples. Therefore, combining these genes in a real-time PCR assay represents a powerful new approach to diagnosing PCa by molecular profiling. (Supplemental material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.) PMID:15609297
Landers, Kelly A; Burger, Michelle J; Tebay, Michelle A; Purdie, David M; Scells, Betty; Samaratunga, Hemamali; Lavin, Martin F; Gardiner, Robert A
Reduction or depletion of mitochondrial DNA (mtDNA) has been associated with cancer progression. Although imbalanced mtDNA content is known to occur in prostate cancer, differences in mtDNA content between African American (AA) and Caucasian American (CA) men are not defined. We provide the first evidence that tumors in AA men possess reduced level of mtDNA compared to CA men. The median tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in normal prostate tissues of AA men compared to CA men, suggesting a possible predisposition to cancer in AA men. mtDNA content was also reduced in benign prostatic hyperplasia (BPH) tissue from AA men. Tumor and BPH tissues from patients ?60 years of age possess reduced mtDNA content compared to patients <60 years of age. In addition, mtDNA content was higher in normal tissues from patients with malignant T3 stage disease compared to patients with T2 stage disease. mtDNA levels in matched normal prostate tissues were nearly doubled in Gleason grade of >7 compared to ?7, whereas reduced mtDNA content was observed in tumors of Gleason grade >7 compared to ?7. Together, our data suggest that AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men, which could contribute to higher risk and more aggressive prostate cancer in AA men.
Koochekpour, Shahriar; Marlowe, Timothy; Singh, Keshav K.; Attwood, Kristopher; Chandra, Dhyan
The prostate-specific antigen test has been a major factor in increasing awareness and better patient management of prostate cancer (PCA), but its lack of specificity limits its use in diagnosis and makes for poor early detection of PCA. The objective of our studies is to identify better bio- markers for early detection of PCA using protein profiling technologies that can
Bao-Ling Adam; Yinsheng Qu; John W. Davis; Michael D. Ward; Lisa H. Cazares; O. John Semmes; Paul F. Schellhammer; Yutaka Yasui; Ziding Feng; George L. Wright
This dissertation examines the long-term cost-effectiveness and cost-consequences of treatment alternatives for the treatment of BPH over a 20-year period using a Markov model. Treatment alternatives compared included watchful waiting, pharmaceuticals (al...
A. K. Biddle D. B. Christensen H. A. Guess J. A. Mauskopf K. E. Kilpatrick R. L. DiSantostefano
Prostatic arterial embolization (PAE) for relief of lower urinary tract symptoms (LUTS) in patients with prostate enlargement or benign prostatic hyperplasia (PE or BPH) is an experimental procedure with promising preliminary results. Patient evaluation and selection before PAE is paramount to improve technical and clinical results. Our inclusion criteria for PAE include: male patients, age>40 years, prostate volume>30 cm(3) and diagnosis of PE or BPH with moderate to severe LUTS refractory to medical treatment for at least 6 months (International Prostate Symptom Score [IPSS]>18, or quality of life [QoL]>3, or both) or with acute urinary retention refractory to medical therapy. Exclusion criteria include: malignancy (based on pre-embolization digital rectal and transrectal ultrasound [TRUS] examinations and prostate specific antigen [PSA] measurements with positive biopsy), large bladder diverticula, large bladder stones, chronic renal failure, tortuosity and advanced atherosclerosis of a) iliac or b) prostatic arteries on pre-procedural computed tomographic angiography (CTA), active urinary tract infection and unregulated coagulation parameters. Approximately one-third of the patients seen initially on consultation satisfy the criteria to be selected for PAE after undergoing the pre-procedural patient evaluation workflow. In the pre-procedural consultation patients are informed of all possible therapeutic options for LUTS with the investigational nature of the procedure being strongly reinforced. The major advantage of PAE relies on the minimally-invasive nature of the technique with minimal morbidity and rapid recovery,and it being performed as an outpatient procedure. However, the experimental nature and uncertain clinical outcome should also be weighed before opting for PAE. All these considerations should be explained to the patient and discussed during the informed consent before PAE. PMID:23244723
A Pereira, José; Bilhim, Tiago; Duarte, Marisa; Rio Tinto, Hugo; Fernandes, Lúcia; Martins Pisco, João
Transurethral resection of the prostate (TURP) is the surgical standard which is truly minimally invasive by using a natural orifice and is also of durable efficacy. The use of TURP removes tissue from benign prostatic hyperplasia (BPH) and leads to clinically relevant improvement in symptoms and quality of life as well as in micturition parameters and obstruction. Tissue is removed by high frequency (HF) current with synchronous hemostasis. Many modifications of TURP, such as the use of video, have become generally accepted and improved the standard. Other modifications were developed because the balance between cutting and hemostasis needed improvement in favor of hemostasis. Several modifications of TURP, such as modulation of HF pulses, band loops and bipolar resection and new procedures, such as vaporization and enucleation showed improved hemostasis. These modifications and procedures, however, have not yet replaced standard TURP but have become established as additional options. PMID:23459921
Muschter, R; Bach, T; Seitz, M
Nocturia is defined as the patient's complaint of having to get up once or several times during the night to urinate, with each voiding preceded and followed by a period of sleep. The direct consequence of nocturia is impaired quality of sleep. The decreased daytime energy is responsible for depression and metabolic disorders and an indirect increase of mortality. Nocturia is a difficult problem to treat in the management of BPH. An effective treatment against nocturia can improve quality of life by acting on quality of sleep. Alpha-blockers, which control these symptoms, are a major component of treatment. However, the dosage forms available are often pharmacologically dependent on dosing conditions, and do not allow maintenance of constant blood levels of the drug. The OCAS (Oral Controlled Absorption System) form of tamsulosin allows absorption of the drug throughout gastrointestinal tract and maintenance of a constant plasma concentration over the 24-hour period. PMID:17969786
Cornu, Jean-Nicolas; Rouprêt, Morgan
... not cancerous. It is very common in older men. An enlarged prostate may make it very difficult to urinate or cause dribbling after you urinate. You may feel the need to urinate a lot, often at night. See your family doctor for an exam. Treatments for BPH include: Watchful waiting, also called ...
Purpose The aim of the present study was to evaluate the effects of low-dose tamsulosin on sexual function in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia. Materials and Methods A total of 138 male LUTS patients aged more than 50 years with an International Prostate Symptom Score (IPSS) ?8 were enrolled in this open-label, multicenter, prospective, noncomparative observational study. Clinical assessments included IPSS, quality of life (QoL) index, International Index of Erectile Function (IIEF), Danish Prostate Symptom Score (DAN-PSS), and an early morning erection questionnaire. The data were recorded at baseline and at 1 and 3 months after treatment with tamsulosin 0.2 mg/d. Adverse events were analyzed in all patients. Results During the study period of 3 months, the IPSS and QoL index significantly improved from baseline by -11.40±9.40 and -1.11±1.36, respectively (p<0.001). However, there were no clinically relevant changes in total IIEF score (mean difference, 1.63±15.50; p=0.406) or the 5 subdomains (p>0.05). Furthermore, DAN-PSS weighted scores (A×B) showed no clinically relevant changes (mean difference on Q1, Q2, and Q3: -0.45±2.94, 0.27±2.50, and -1.27±2.27, p>0.05). In addition, there were no clinically significant changes in responses on the early morning erection questionnaire. Conclusions Tamsulosin at the dose of 0.2 mg significantly improved the IPSS and the QoL index compared with baseline. However, tamsulosin did not exhibit any significant impact on sexual function or any negative impact on ejaculatory function.
Kim, Sin Wook; Lee, Wan Cheol; Kim, Ma Tae; Ko, Kyungtae; Lee, Won Ki; Lee, Choong-Hyun; Kim, Je Jong
Purpose: To study the safety and efficacy of a new high-power potassium-titanyl-phosphate laser (KTP\\/532; Niagara PV™ laser system; Laserscope, San Jose, CA) for transurethral photoselective vaporization of be- nign obstructive prostate tissue. Patients and Methods: The KTP\\/532 laser energy at 80 W was delivered by a 6F side-firing fiber through a 23F continuous-flow cystoscope. Photoselective vaporization of the prostate (PVP)
Mahmood A. Hai; Reza S. Malek
Incidental prostate cancer (PCa) after treatment of benign prostate hyperplasia (BPH) is becoming less common. This is a result of the changing patterns of BPH treatment. The purpose of the present research was to re-examine the clinical outcomes and importance of cT1a and cT1b PCa in a contemporary cohort after holmium laser enucleation of the prostate (HoLEP). All patients with newly diagnosed PCa after HoLEP were retrospectively identified. Pre- and postoperative prostate-specific antigen (PSA), biopsy history, pathological features and disease progression were examined. Patients were matched to a control group with benign pathology for outcome comparisons. The database consisted of 240 consecutive patients, aged 52-90 years with prostate sizes from 25 to 375?cm(3) . A total of 28 patients were identified with incidental PCa (14 cT1a and 14 cT1b). Median follow up was 11 months and 13 months for cT1a and cT1b, respectively. Hospitalization time, catheterization time, complications and functional outcomes were similar. Three patients with cT1b required additional treatment as a result of PSA progression. All other cancers are being closely followed. The functional benefits of HoLEP are well established. The incidental PCa detection rate of 11.7% shows the potential benefit of pathological analysis. Just 10.7% of these patients received additional treatment, but this might be significant as these patients would otherwise go untreated. The impact on disease-specific survival and progression requires a longer follow up. PMID:21592233
Nunez, Rafael; Hurd, Kimberly J; Noble, Brie N; Castle, Erik P; Andrews, Paul E; Humphreys, Mitchell R
Prostate-specific antigen (PSA) is an androgen-dependent glycoprotein protease (M.W. 33 kDa) and a member of kallikrein super-family of serine protease, and has chymotrypsin-like enzymatic activity. It is synthesized by the prostate epithelial cells and found in the prostate gland and seminal plasma as a major protein. It is widely used as a clinical marker for diagnosis, screening, monitoring and prognosis of prostate cancer. In normal male adults, the concentration of PSA in the blood is below 4 ng/ml and this value increases in patients with the prostate cancer or the benign prostatic hyperplasia (BPH) due to its leakage into the circulatory system. As such, systematic monitoring of the PSA level in the blood can provide critical information about the progress of the prostatic disease. We have developed a compact integral system that can quantitatively measure the concentration of total PSA in human blood. This system utilizes the fluorescence emitted from the dye molecules attached to PSA molecules after appropriate immunoassay-based processing. Developed for the purpose of providing an affordable means of fast point-of-care testing of the prostate cancer, this system proved to be able to detect the presence of the PSA at the level of 0.18 ng/ml in less than 12 minutes, with the actual measurement taking less than 2 minutes. The design concept for this system is presented together with the result for a few representative samples.
Kim, Byeong C.; Jeong, Jin H.; Jeong, Dong S.; Kim, Young M.; Oh, Sang W.; Choi, Eui Y.; Kim, Jae H.; Nahm, Kie B.
We have examined the expression of 2 tumor-associated metalloproteinases, MMP-2 and MMP-9, in 48 primary cultures of prostatic carcinoma (PRCA) and 33 cultures of benign prostatic hyperplasia (BPH). PRCA cultures secrete significantly more MMP-9 than their benign counterparts. Secreted MMP-2 did not differ significantly in cultures but was lower in PRCA cultures. Two cultures of benign origin exhibited high MMP-9 secretion and growth patterns consistent with a malignancy. Both cases were followed and successively re-evaluated histologically and rediagnosed as organ-confined PRCA. MMP expression in culture may be of predictive value in the identification of incidental PRCA. MMP-9 secretion and its ratio with MMP-2 were highest in epithelial cultures from invasive, metastatic tumors when compared both to disease confined to prostate gland and to locally extensive disease. MMP-9 secretion was greatest also in cultures derived from tissues of high Gleason histological grade. Active MMP-9 species were detected in 15 cultures (31%) of PRCA. Active MMP-2 species were observed in cultures of both BPH and PRCA origin in almost the same amounts. Although average levels were not significantly different, as a ratio to proform species, a significant elevation was observed in cultures of PRCA origin. We propose, therefore, that an elevated expression of MMP-9 and a high ratio of MMP-9 to MMP-2 in short-term prostate epithelial cultures is of potential diagnostic and prognostic significance. PMID:8900372
Festuccia, C; Bologna, M; Vicentini, C; Tacconelli, A; Miano, R; Violini, S; Mackay, A R
Tamsulosin Oral Controlled Absorption System (OCAS) in Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia (LUTS\\/BPH): Efficacy and Tolerability in a Placebo and Active Comparator Controlled Phase 3a Study
Objectives:This phase 3a study assessed the efficacy and safety of two different doses of a new formulation of tamsulosin (the oral controlled absorption system: OCAS) in comparison with placebo and the old modified release (MR) formulation of tamsulosin.
Christopher R. Chapple; Salman H. Al-Shukri; Bernard Gattegno; Simon Holmes; José M. Martínez-Sagarra; Roberto M. Scarpa; Oncko B. van Vierssen Trip; Viktor Vik; Ingrid van der Putten-Slob
Tamsulosin Oral Controlled Absorption System (OCAS) in Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia (LUTS\\/BPH): Efficacy and Tolerability in a Phase 2b Dose-Response Study
Objectives:This phase 2b randomised, placebo-controlled trial (RCT) was a dose-response study to assess the efficacy and safety of three different doses of a new formulation of tamsulosin (the oral controlled absorption system: OCAS) and to determine which dose(s) should be further evaluated in a phase 3a RCT.
Christopher R. Chapple; Jerzy Lorenz; Raymond Mortensen; Harald Pauthner; Mario O. Reis; Claude C. Schulman; Ingrid van der Putten-Slob
Background Gene expression profiling has recently shown that the mRNA for CD24 is overexpressed in prostate carcinomas (Pca) compared to benign or normal prostate epithelial tissues. Immunohistochemical studies have reported the usefulness of anti-CD24 for detecting prostate cancer over the full range of prostate specimens encountered in surgical pathology, e.g. needle biopsies, transurethral resection of prostate chips, or prostatectomies. It is a small mucin-like cell surface protein and thus promises to become at least a standard adjunctive stain for atypical prostate biopsies. We tested the usefulness of real-time RT-PCR for specific and sensitive detection of CD24 transcripts as a supplementary measure for discriminating between malignant and benign lesions in prostatic tissues. Methods Total RNA was isolated from snap-frozen chips in 55 cases of benign prostatic hyperplasia (BPH) and from frozen sections in 59 prostatectomy cases. The latter contain at least 50% malignant epithelia. Relative quantification of CD24 transcripts was performed on the LightCycler instrument using hybridization probes for detection and porphobilinogen deaminase transcripts (PBGD) for normalization. Results Normalized CD24 transcript levels showed an average 2.69-fold increase in 59 Pca-cases (mean 0.21) when compared to 55 cases of BPH (mean 0.08). This difference was highly significant (p < 0.0001). The method has a moderate specificity (47.3%) but a high sensitivity (86.4%) if the cutoff is set at 0.0498. CD24 expression levels among Pca cases were not statistically associated with the tumor and lymph-node stage, the grading (WHO), the surgical margins, or the Gleason score. Conclusion The present study demonstrates the feasibility of quantitative CD24 RNA transcript detection in prostatic tissues even without previous laser microdissection.
Schostak, M; Krause, H; Miller, K; Schrader, M; Weikert, S; Christoph, F; Kempkensteffen, C; Kollermann, J
Objective: The objective of this paper is to examine safety and tolerability data from a number of recently completed clinical trials with the novel, dual 5?-reductase inhibitor, dutasteride.Methods: Intent-to-treat analyses were conducted on data for dutasteride 0.5mg\\/day for drug-related adverse events, clinical laboratory test results, and prostate-specific antigen (PSA) levels derived from four large, randomised, double-blind clinical trials (n=5655). Further
Gerald L Andriole; Roger Kirby
Type A neurotoxin (NTX) of Clostridium botulinum was purified by a simple procedure using a lactose gel column. The toxicity of this purified toxin preparation was retained for at least 1 year at -30°C by supplementation with either 0.1% albumin or 0.05% albumin plus 1% trehalose. When purified NTX was used to treat 49 patients with urinary incontinence caused by either refractory idiopathic or neurogenic detrusor overactivity, 36 patients showed significant improvement in symptoms. These beneficial effects were also observed in cases of prostatic hyperplasia. The results obtained with NTX were similar to that of Botox. The effects of NTX on trigeminal neuralgia induced by infraorbital nerve constriction (IoNC) in rats were also studied. Trigeminal ganglion neurons from ipsilateral to IoNC exhibited significantly faster onset of FM4-64 release than sham-operated contralateral neurons. Intradermal injection of NTX in the area of IoNC alleviated IoNC-induced pain behavior and reduced the exaggerated FM4-64 release in trigeminal ganglion neurons. PMID:22745637
Matsuka, Yoshizo; Yokoyama, Teruhiko; Yamamoto, Yumiko; Suzuki, Tomonori; Dwi Fatmawati, Ni Nengah; Nishikawa, Atsushi; Ohyama, Tohru; Watanabe, Toshihiro; Kuboki, Takuo; Nagai, Atsushi; Oguma, Keiji
Type A neurotoxin (NTX) of Clostridium botulinum was purified by a simple procedure using a lactose gel column. The toxicity of this purified toxin preparation was retained for at least 1 year at ?30°C by supplementation with either 0.1% albumin or 0.05% albumin plus 1% trehalose. When purified NTX was used to treat 49 patients with urinary incontinence caused by either refractory idiopathic or neurogenic detrusor overactivity, 36 patients showed significant improvement in symptoms. These beneficial effects were also observed in cases of prostatic hyperplasia. The results obtained with NTX were similar to that of Botox. The effects of NTX on trigeminal neuralgia induced by infraorbital nerve constriction (IoNC) in rats were also studied. Trigeminal ganglion neurons from ipsilateral to IoNC exhibited significantly faster onset of FM4-64 release than sham-operated contralateral neurons. Intradermal injection of NTX in the area of IoNC alleviated IoNC-induced pain behavior and reduced the exaggerated FM4-64 release in trigeminal ganglion neurons.
Matsuka, Yoshizo; Yokoyama, Teruhiko; Yamamoto, Yumiko; Suzuki, Tomonori; Dwi Fatmawati, Ni Nengah; Nishikawa, Atsushi; Ohyama, Tohru; Watanabe, Toshihiro; Kuboki, Takuo; Nagai, Atsushi; Oguma, Keiji
Prostate cancer is the most frequently diagnosed cancer in American men. Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer, but elevated serum PSA levels may be present in non-malignant conditions such as benign prostatic hyperlasia (BPH). Characterization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidate clinical biomarkers,
Saravana M. Dhanasekaran; Terrence R. Barrette; Debashis Ghosh; Rajal Shah; Sooryanarayana Varambally; Kotoku Kurachi; Kenneth J. Pienta; Mark A. Rubin; Arul M. Chinnaiyan
Purpose To describe the cross-sectional associations of benign prostate-specific antigen (BPSA) with clinical urologic measures, and to examine the risk of future urologic outcomes in two population-based cohorts of black and white men. Materials and Methods Two population-based, cohort studies were established to characterize the natural history and risk factors for progression of prostate disease in white and black male residents of Olmsted County, Minnesota and Genesee County, Michigan, respectively. Results The distribution of BPSA levels was similar in blacks (median (25th, 75th percentiles) =32.9 (17.3, 68.0) pg/mL) and whites (median=32.2 (16.6,68.9) pg/mL), p=0.71, but much lower than previous reports. For Olmsted County men in the upper quartile of BPSA, there was a 15-fold increased risk of prostate cancer (CaP; hazard ratio (HR): 14.6 95% confidence interval (CI): 3.1, 68.6) and a 2-fold higher risk of treatment for benign prostatic hyperplasia (BPH; HR: 2.2, 95% CI: 1.2, 4.2) after adjusting for age. After additional adjustment for baseline PSA, the association between BPSA and CaP risk was attenuated, but remained nearly 9-fold higher for men in the upper BPSA quartile (HR: 8.7, 95% CI: 1.8, 42.4). The 2-fold higher risk of treatment for BPH also remained after adjustment for baseline PSA for men in the upper BPSA quartile (HR: 1.9, 95% CI: 0.9, 4.0). Conclusions These results suggest that elevated BPSA level may help to identify men at risk of treatment for BPH and identify men with prostate cancer.
RHODES, THOMAS; JACOBSON, DEBRA J.; MCGREE, MICHAELA E.; ST SAUVER, JENNIFER L.; SARMA, ARUNA V.; GIRMAN, CYNTHIA J.; LIEBER, MICHAEL M.; KLEE, GEORGE G.; DEMISSIE, KITAW; JACOBSEN, STEVEN J.
Tumor microenvironment modifications are related to the generation of reactive stroma and to critical events in cancer progression, such as proliferation, migration and apoptosis. In order to clarify these cellular interactions mediated by reactive stroma, we investigated the effects of cell-cell contacts, and the influence of soluble factors and extracellular matrix (ECM) secreted by Benign Prostate Hyperplasia (BPH) reactive stroma over LNCaP prostate tumor cells. Using in vitro functional assays, we demonstrated that ECM strongly stimulated LNCaP cell proliferation and migration, while inhibiting apoptosis, and inducing a deregulated expression pattern of several genes related to prostate cancer (PCa) progression. Conversely, reactive stromal cells per se and their secreted conditioned medium partially modulated these pro-tumorigenic events. These data indicate that secreted ECM in reactive stroma microenvironment contains key molecules that positively modulate important cancer hallmarks. PMID:22388175
Palumbo, Antonio; Ferreira, Luciana Bueno; Reis de Souza, Pedro A V; Oliveira, Felipe Leite de; Pontes, Bruno; Viana, Nathan B; Machado, Daniel Escorsim; Palmero, Celia Yelimar; Alves, Leandro M; Gimba, Etel R P; Nasciutti, Luiz E
The laboratory diagnosis of acute bacterial prostatitis is straightforward and easily accomplished in clinical laboratories. Chronic bacterial prostatitis, and especially chronic idiopathic prostatitis (most often referred to as abacterial prostatitis), presents a real challenge to the clinician and clinical microbiologist. Clinically, the diagnosis of chronic idiopathic prostatitis is differentiated from that of acute prostatitis by a lack of prostatic inflammation and no “significant” (controversial) leukocytes or bacteria in the expressed prostatic secretions. Despite these diagnostic criteria, the etiology of chronic idiopathic prostatitis is unknown. While this review covers the entire spectrum of microbially caused acute prostatitis (including common and uncommon bacteria, viruses, fungi, and parasites) and microbially associated chronic prostatitis, a special focus has been given to chronic idiopathic prostatitis. The idiopathic syndrome is commonly diagnosed in men but is poorly treated. Recent data convincingly suggests a possible bacterial etiology for the condition. Provocative molecular studies have been published reporting the presence of 16S rRNA bacterial sequences in prostate biopsy tissue that is negative for ordinary bacteria by routine culture in men with chronic idiopathic prostatitis. Additionally, special culture methods have indicated that difficult-to-culture coryneforms and coagulase-negative staphylococci are present in expressed prostatic secretions found to be negative by routine culture techniques. Treatment failures are not uncommon in chronic prostatitis. Literature reports suggest that antimicrobial treatment failures in chronic idiopathic prostatitis caused by organisms producing extracellular slime might result from the virulent properties of coagulase-negative staphylococci or other bacteria. While it is difficult to definitively extrapolate from animal models, antibiotic pharmokinetic studies with a murine model have suggested that treatment failures in chronic prostatitis are probably a result of the local microenvironment surrounding the persistent focal and well-protected small bacterial biofilms buried within the prostate gland. These conclusions support the molecular and culture data implicating bacteria as a cause of chronic idiopathic prostatitis.
Domingue, Gerald J.; Hellstrom, Wayne J. G.
Heart failure (HF) and benign prostatic hypertrophy (BPH) are two conditions that commonly coexist in men 60 years and older. Carvedilol is the only ?-adrenergic blocker approved for HF that also has additional ?1-adrenergic blockade. As ?1-adrenergic blockers are used in the treatment of BPH, it is intuitive that carvediolol could improve BPH symptoms. We present a case where carvedilol
Colleen K. Rohrer; Robert Lee Page; Simon F. Shakar; JoAnn Lindenfeld
It has been demonstrated that the glutathione S-transferase (GST) superfamily helps remove carcinogens from the body and thus might be associated with prostate cancer risk. In recent years, GSTT1 polymorphism has been extensively studied as a potential prostate cancer risk factor; however, the results are inconsistent. To investigate the association between GSTT1 and prostate cancer, we conducted a meta-analysis of 33 studies with 6,697 prostate patients and 7,643 controls. For GSTM1 null versus present genotype, the random effects odds ratio was 0.98 (95 % confidence interval (CI) 0.83-1.16) based on a wide population. Subgroup analyses in the different ethnic groups and different controls were performed. The OR was 1.01 (95 % CI 0.86-1.19) in Caucasians, 1.01 (95 % CI 0.70-1.47) in Asians, and 0.77 (95 % CI 0.42-1.42) in Africans. The OR was 0.98 (95 % CI 0.82-1.16) in non-benign prostate hyperplasia (BPH) controls and 1.09 (95 % CI 0.66-1.79) in BPH controls. In conclusion, our present meta-analysis demonstrates that there is no association between GSTT1 polymorphism and prostate cancer, even in the sub-analysis concerning different races and control sources. The direction of further research should focus not only on the simple relationship of GSTT1 and prostate cancer but also on gene-environment interaction and distinctions of different GSTs. PMID:23456766
Wang, Jihong; Xu, Yuemin; Fu, Qiang; Yu, Jianjun; Chen, Zhong; Liu, Zhangshun; Li, Chao; Guo, Hui; Xie, Mingkai
Background: The aim of this study was to determine the relationship between body mass index, biochemical parameters, and 5-hydroxytryptamine (5-HT) genetic polymorphisms and prostate dysfunction in an elderly general male population. Results: One hundred and seventeen elderly male subjects [60 men without symptoms of prostate hyperplasia, 42 men with untreated benign prostatic hyperplasia (BPH), and 15 men with prostate cancer (PCa)] treated with finasteride or flutamide were included. Multiple comparisons showed significant difference in age, T-score, concentration of phosphorus, calcium, C-reactive protein, and prostate-specific antigen (PSA) between the groups. T-score was the lowest and phosphorus concentration was the highest in the PCa group. Highest PSA, proteins, calcium, and Hekal's formula score were found in the BPH group. Patients with PCa were more frequent GG+GA carriers of 5-HT1B 1997A/G gene polymorphism (p=0.035). Univariate regression analysis showed association of PCa-treated subjects with age (p=0.010) and 5-HT1B genetic polymorphism (p=0.018). Antiandrogen therapy affects T-score (p=0.017), serum phosphorus (p=0.008), glucose (p=0.036), and total proteins (p=0.050). Multivariate-stepwise logistic regression analysis showed the significant association of treated PCa with age (p=0.028) and inorganic phosphorus (p=0.005), and a marginal association with ultrasonographic T-score (p=0.052). Conclusions: Antiandrogen therapy might induce bone mineral loss in elderly PCa patients. Preliminary data imply that the genetic variants of the 5-HT1B receptor might be associated with PCa.
Paukovic, Paulina; Cvijetic, Selma; Pizent, Alica; Jurasovic, Jasna; Milkovic-Kraus, Sanja; Dodig, Slavica; Muck-Seler, Dorotea; Mustapic, Maja; Pivac, Nela; Lana-Feher-Turkovic; Pavlovic, Mladen
Oral anticoagulation (OA) has been considered as a strict contraindication to transurethral resection of the prostate (TURP). In recent years, some studies have shown that holmium laser enucleation of the prostate (HoLEP) has less blood loss compared to TURP. Thus we have performed HoLEP in patients with benign prostatic hyperplasia (BPH) under continuous OA from September 2009, and herein we report our first nine cases. Patients received HoLEP by a single surgeon at our institution. HoLEP was performed successfully in all patients. The mean times to complete enucleation and morcellation were 48.2 and 5.1 minutes, respectively. The mean tissue weight of enucleation was 37 grams. The mean hemoglobin and sodium loss after HoLEP were 1.7 g/dl and 1.3 mEq/L, respectively, and the catheterization time was 1.6 days. Blood transfusion, clot retention or transurethral resection syndrome were not observed in any cases. HoLEP has excellent hemostatic properties, and is a safe and effective procedure for patients with symptomatic BPH under the condition of continuous OA. PMID:21174742
Hirayama, Takahiro; Shitara, Toshiya; Fujita, Tetsuo; Iwamura, Masatsugu; Kubo, Seiichi; Baba, Shiro
Prostatic development is induced by androgens acting via mesenchymal-epithelial interactions. Androgens elicit their morphogenetic effects by acting through androgen receptors (ARs) in urogenital sinus mesenchyme (UGM), which induces prostatic epithelial development. In adulthood reciprocal homeostatic stromal-epithelial interactions maintain functional differentiation and growth-quiescence. Testosterone plus estradiol (T+E2) have been shown to induce prostatic carcinogenesis in animal models. Thus, tissue recombinant studies were undertaken to explore the mechanisms of prostatic carcinogenesis in BPH-1 cells in which ARs and estrogen receptors (ERs) are undetectable. For this purpose, BPH-1 cells were combined with UGM, and the UGM+BPH-1 recombinants were grafted to adult male hosts. Solid branched epithelial cords and ductal structures formed in untreated UGM+BPH-1 recombinants. Growth was modest, and tumors did not develop. UGM+BPH-1 recombinants treated with T+E2 formed invasive carcinomas. BPH-1 cells lack ARs and ERs, whereas rat UGM expresses both of these receptors. These data show that immortalized nontumorigenic human prostatic epithelial cells can undergo hormonal carcinogenesis in response to T+E2 stimulation via paracrine mechanisms and demonstrate that the stromal environment plays an important role in mediating hormonal carcinogenesis. During prostatic carcinogenesis the stroma undergoes progressive loss of smooth muscle with the appearance of carcinoma-associated fibroblasts (CAF). This altered stroma was tested for its ability to promote carcinogenesis of nontumorigenic but immortalized human prostatic epithelial cells (BPH-1). CAF+BPH-1 tissue recombinants formed large carcinomas. In contrast, recombinants composed of normal prostatic stroma+BPH-1 cells exhibited minimal growth. This stroma-induced malignant transformation was associated with additional genetic alterations and changes in gene expression. Thus, alteration in the stromal microenvironment was sufficient to promote malignant transformation of human prostatic epithelial cells. PMID:12492490
Cunha, Gerald R; Hayward, Simon W; Wang, Y Z
Epithelial-mesenchymal transition (EMT) is implicated in various pathological processes within the prostate, including benign prostate hyperplasia (BPH) and prostate cancer progression. However, an ordered sequence of signaling events initiating carcinoma-associated EMT has not been established. In a model of transforming growth factor ? (TGF?)-induced prostatic EMT, SLUG is the dominant regulator of EMT initiation in vitro and in vivo, as demonstrated by the inhibition of EMT following Slug depletion. In contrast, SNAIL depletion was significantly less rate limiting. TGF?-stimulated KLF4 degradation is required for SLUG induction. Expression of a degradation-resistant KLF4 mutant inhibited EMT, and furthermore, depletion of Klf4 was sufficient to initiate SLUG-dependent EMT. We show that KLF4 and another epithelial determinant, FOXA1, are direct transcriptional inhibitors of SLUG expression in mouse and human prostate cancer cells. Furthermore, self-reinforcing regulatory loops for SLUG-KLF4 and SLUG-FOXA1 lead to SLUG-dependent binding of polycomb repressive complexes to the Klf4 and Foxa1 promoters, silencing transcription and consolidating mesenchymal commitment. Analysis of tissue arrays demonstrated decreased KLF4 and increased SLUG expression in advanced-stage primary prostate cancer, substantiating the involvement of the EMT signaling events described in model systems.
Liu, Yen-Nien; Abou-Kheir, Wassim; Yin, Juan Juan; Fang, Lei; Hynes, Paul; Casey, Orla; Hu, Dong; Wan, Yong; Seng, Victoria; Sheppard-Tillman, Heather; Martin, Philip
Prostate cancer (PCa) is the most common noncutaneous cancer among men, accounting for 10 % of male cancer-related deaths worldwide. The etiology of PCa is largely unknown, although multiple environmental and lifestyle factors such as ultraviolet irradiation, smoking, and diet might increase the risk of the disease. Risk of disease varies most prominently with age, ethnicity, family history, and diet. The multifunctional cytokine tumor necrosis factor alpha (TNF-?) has an important role in the pathogenesis of inflammatory, autoimmune and malignant diseases. In this case control study 150 Prostate cancer patients and 150 age matched benign prostate hyperplasia (BPH) and equal number of healthy control groups were involved. The aim of this study was to analyze the effect of TNF-?-308 (G/A) polymorphism on risk of prostate cancer on north Indian prostate cancer patients. The polymerase chain reaction (PCR) technique was utilized to genotype TNF-?-308 (G/A) polymorphism. The present study showed statistically significant increased risk of prostate cancer among individuals that carried the A allele of TNF-?-308 gene (OR = 1.81, 95 % CI 1.00-3.481, p = 0.03). PMID:23065208
Berhane, Nega; Sobti, Rabinder Chandera; Melesse, Shiferaw; Mahdi, Salih Abdul; Kassu, Afework
The androgens testosterone (T) and dihydrotestosterone (DHT), besides playing an important role in prostate development and growth, are also responsible for the development and progression of benign prostate hyperplasia (BPH) and prostate cancer. Therefore, the actions of these hormones can be antagonized by preventing the irreversible conversion of T into DHT by inhibiting 5?-reductase (5?-R). This has been a useful therapeutic approach for the referred diseases and can be achieved by using 5?-reductase inhibitors (RIs). Steroidal RIs, finasteride and dutasteride, are used in clinic for BPH treatment and were also proposed for chemoprevention of prostate cancer. Nevertheless, due to the increase in bone and muscle loss, impotency and occurrence of high-grade prostate tumours, it is important to seek for other potent and specific molecules with lower side effects. In the present work, we designed and synthesized steroids with the 3-keto-?(4) moiety in the A-ring, as in the 5?-R substrate T, and with carboxamide, carboxyester or carboxylic acid functions at the C-17? position. The inhibitory 5?-R activity, in human prostate microsomes, as well as the anti-proliferative effects of the most potent compounds, in a human androgen-responsive prostate cancer cell line (LNCaP cells), were investigated. Our results showed that steroids 3, 4 and 5 are good RIs, which suggest that C-17? lipophylic amides favour 5?-R inhibition. Moreover, these steroids induce a decrease in cell viability of stimulated LNCaP cells, in a 5?-R dependent-manner, similarly to finasteride. PMID:23933094
Amaral, Cristina; Varela, Carla; Correia-da-Silva, Georgina; Tavares da Silva, Elisiário; Carvalho, Rui A; Costa, Saul C P; Cunha, Sara C; Fernandes, José O; Teixeira, Natércia; Roleira, Fernanda M F
Overexpression of basic fibroblast growth factor (bFGF) has been implicated in the pathogenesis of benign prostatic hyperplasia (BPH) and bFGF has been considered to be a promising therapy target for BPH. RNA interference (RNAi) based therapeutic approaches hold promise for the treatment of a variety of diseases. However, RNAi experiments have seldom been performed in human prostatic stromal cells (PrSCs). In the present study, we transfected adenovirus type 5 vector mediated small hairpin RNA (shRNA) against human bFGF mRNA (Ad-sh-bFGF) to examine the proliferation and apoptosis effects on cultured human primary PrSCs. The gene-silencing effect of shRNA was evaluated by western blot. Cell proliferation was determined by MTT assays. Cell apoptosis was analyzed by flow cytometry and detection of caspase-3 activity. The effect of Ad-sh-bFGF on Bcl-2 gene expression was also examined. Adenovirus type 5 can efficiently delivered shRNA against bFGF into to PrSCs and the level of protein was depressed significantly in cells infected by Ad-sh-bFGF, approximately 50% lower than those cells infected by adenovirus-delivered nonsense shRNA (P < 0.01). Moreover, Ad-sh-bFGF is able to induce apoptosis and inhibit proliferation of cultured human primary PrSCs significantly (P < 0.01). Bcl-2 protein expression was markedly inhibited by transfection with Ad-sh-bFGF. In conclusion, our findings suggest that RNAi delivered via an adenovirus vector offers a prospect of improvement in treatment of BPH and bFGF is a potential target worth exploiting in BPH. PMID:20526813
Wang, Kai; Cheng, Linfeng; Liang, Yinghong; Liu, Donghui; Li, Kai; Wang, Ping
pS2 or TFF1 is a member of the trefoil factor family, which is distributed throughout the gastrointestinal tract in both normal and diseased tissues. It is also considered to be one of the major estrogen-regulated proteins and an indicator of estrogen receptor (ER) functionality. pS2 has previously been investigated in benign and malignant prostate lesions with little information about its relationship to steroid receptor status. Our purpose was to correlate pS2 expression with steroid receptor status (ER alpha and progesterone receptor (PR)) and other pathologic variables in prostate carcinoma. 15 benign prostate hyperplasia (BPH) and 47 prostate carcinoma cases were investigated by means of immunohistochemistry for pS2, ER and PR expression. 80% of BPH showed pS2 cytoplasmic immunoreactivity in hyperplastic acini and about half of these cases also exhibited nuclear staining decorating basal or both basal and luminal nuclei. pS2 was highly expressed in prostate carcinoma (91.4%) with both cytoplasmic and nuclear patterns of staining. The latter pattern was significantly associated with carcinoma having a low Gleason score (p=0.02). pS2 lacked any significant correlation with steroid receptor status, stage or grade. Univariate survival analysis revealed a significant impact of stage (p=0.03) and nodal status (p<0.0001) on patient outcome. The diagnostic value of pS2 expression in prostate carcinoma validated 74.19% accuracy, 91.48% sensitivity and 78.18% positive predictive value. The high sensitivity of pS2 expression in prostate carcinoma could make it a suitable marker for diagnosis of prostate carcinoma, especially in metastatic cases of unknown origin. The absence of correlation and dissimilarity in immunolocalization between pS2 and ER alpha leads to the assumption that ER alpha could not be the regulatory protein for pS2 and may raise questions about the functionality of ER alpha in prostate. The nuclear pattern of pS2 immunoreactivity either in benign or malignant prostatic lesions is similar to the published data on ER beta distribution and could also identify a subset of carcinoma patients with a favorable prognosis. PMID:19132993
Abdou, Asmaa Gaber; Aiad, Hayam Abdel Samie; Sultan, Sultan Mohamed
Identification of aberrant expression patterns of genes in prostate cancer (PCa) is a key step towards the development of effective therapies. Prostate-specific antigen (PSA) levels are commonly measured for the early detection of PCa, but which itself is still not an ideal biomarker. We analysed the expression patterns of prostate cancer susceptibility candidate (PRAC) in prostate cancer. The PRAC gene is known to be commonly expressed in prostate tissue, rectum and colon. To provide clear insights into the expression patterns of PRAC in PCa, we examined the gene expression by quantitative real-time PCR (qRT-PCR), western blot analysis and immunohistochemistry (IHC). The results showed that PRAC expression levels in androgen?insensitive cells (DU145 and PC3) are lower than those in androgen-sensitive cell lines (LNCaP, LNCaP-R and CW22R). However, treatment of the LNCaP cell line with androgen and anti-androgen demonstrated that PRAC is expressed in an androgen-independent manner. Further, PRAC expression was restored upon treatment of DU145 and PC3 cells with the methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-CdR), which indicates the effect of methylation in the control of PRAC expression. In addition, IHC analysis revealed a significantly decreased immunoreactivity of PRAC protein in PCa tissues compared to benign prostatic hyperplasia (BPH) (p<0.0001). Thus, our findings suggest that the pathogenesis of PCa may be due to the expression levels of PRAC protein, and this protein can serve as a potential biomarker for the management of PCa. PMID:24100630
Lenka, Govinda; Weng, Wen-Hui; Chuang, Cheng-Keng; Ng, Kwai-Fong; Pang, See-Tong
Purpose: Initially conceived as an intervention for prostatic infection, injection therapy has been used to alleviate urinary retention, and is now primarily investigated for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). For over a century, intraprostatic injection has been used as a minimally invasive surgical therapy (MIST), and is on the verge of a rebirth. This review will familiarize the reader with the origins and history of intraprostatic injection, and its evolution using transperineal, transrectal and transurethral routes with multiple injectants. Materials and Methods: A MEDLINE review of the literature on intraprostatic injections published between 1966 and 2007 was performed, augmented with articles and documents dating back to 1832. Results: Transperineal and transurethral injections have the most systematic evaluation in patients. There are advantages and disadvantages associated with each route. Most injectants consistently produce localized coagulative necrosis and gland volume reduction with varying degrees of LUTS relief. Anhydrous ethanol (AE) is the most extensively studied injected agent to date. Conclusions: Injection therapy is a promising minimally invasive treatment option for various prostatic conditions and has been examined for over 100 years. Further experience in systematic laboratory research and completion of currently ongoing clinical trials is necessary before widespread clinical application.
Saemi, Arash M.; Folsom, Jeffrey B.; Plante, Mark K.
Recent studies underline the implication of Liver X Receptors (LXRs) in several prostate diseases such as benign prostatic hyperplasia (BPH) and prostate cancer. In order to understand the molecular mechanisms involved, we derived epithelial cells from dorsal prostate (MPECs) of wild type (WT) or Lxr??-/- mice. In the WT MPECs, our results show that LXR activation reduces proliferation and correlates with the modification of the AKT-survival pathway. Moreover, LXRs regulate lipid homeostasis with the regulation of Abca1, Abcg1 and Idol, and, in a lesser extent, Srebp1, Fas and Acc. Conversely cells derived from Lxr??-/- mice show a higher basal phosphorylation and consequently activation of the survival/proliferation transduction pathways AKT and MAPK. Altogether, our data point out that the cell model we developed allows deciphering the molecular mechanisms inducing the cell cycle arrest. Besides, we show that activated LXRs regulate AKT and MAPK transduction pathways and demonstrate that LXRs could be good pharmacological targets in prostate disease such as cancer. PMID:23554947
Dufour, Julie; Pommier, Aurélien; Alves, Georges; De Boussac, Hugues; Lours-Calet, Corinne; Volle, David H; Lobaccaro, Jean-Marc A; Baron, Silvère
Thermal ablation is a minimally-invasive treatment option for benign prostatic hyperplasia (BPH) and localized prostate cancer. Accurate spatial control of thermal dose delivery is paramount to improving thermal therapy efficacy and avoiding post-treatment complications. We have recently developed three types of transurethral ultrasound applicators, each with different degrees of heating selectivity. These applicators have been evaluated in vivo in coordination with magnetic resonance temperature imaging, and demonstrated to accurately ablate specific regions of the canine prostate. A finite difference biothermal model of the three types of transurethral ultrasound applicators (sectored tubular, planar, and curvilinear transducer sections) was developed and used to further study the performance and heating capabilities of each these devices. The biothermal model is based on the Pennes bioheat equation. The acoustic power deposition pattern corresponding to each applicator type was calculated using the rectangular radiator approximation to the Raleigh Sommerfield diffraction integral. In this study, temperature and thermal dose profiles were calculated for different treatment schemes and target volumes, including single shot and angular scanning procedures. This study also demonstrated the ability of the applicators to conform the cytotoxic thermal dose distribution to a predefined target area. Simulated thermal profiles corresponded well with MR temperature images from previous in vivo experiments. Biothermal simulations presented in this study reinforce the potential of improved efficacy of transurethral ultrasound thermal therapy of prostatic disease.
Ross, Anthony B.; Diederich, Chris J.; Nau, William H.; Tyreus, Per D.; Gill, Harcharan; Bouley, Donna; Butts, R. K.; Rieke, Viola; Daniel, Bruce; Sommer, Graham
High Intensity Focused Ultrasound (HIFU) has been clinically used for the treatment of benign prostatic hyperplasia (BPH) and it is experimentally applied for the treatment of localized prostate caner (PC). Recent advances in the transducer material and technology have permitted to combine the ultrasound visualization capability and HIFU on the same ceramic crystal. Also, the transducer efficiency has increased to a level that a smaller size intracavity probe can be made to produce sufficient acoustic power required for the focused ultrasound surgery of the prostate. Using this technology, 4 MHz mechanically scanning transrectal ultrasound probes has been designed. The transrectal probes are used with Sonablate (SB-200, manufactured by Focus Surgery, Inc., Indianapolis, IN) device. The SB-200 produces both transverse and longitudinal images of the prostate. The transverse and longitudinal images are used for selection of tissue volume, treatment planning and monitoring of tissue during the HIFU treatment cycle. The paper reviews the present operation of the device and recent clinical protocol that has improved efficiency, efficacy and safety of the device. The two years follow-up clinical results from the multi-site US Pilot Study (USPS) and The Male Health Centre are compared with the Kitasato-study (Kitasato School of Medicine, Sagamihara, Japan).
Sanghvi, Narendra T.; Syrus, J.; Foster, Richard S.; Bihrle, Richard; Casey, Richard W.; Uchida, Toyoak
The aim of this study was determined the expression of pro inflammatory cytokines in prostate epithelial cells. Furthermore,\\u000a we analysed the relation between these cytokines and sera PSA levels according the three groups: 0–4, 4–20 and >20 ng\\/mL.\\u000a The study was carried out in five normal prostate (NP), 27 benign prostate hyperplastic (BPH) and 18 prostate cancer (PC).\\u000a Immunohistochemical and Western
Yosra Bouraoui Mechergui; Awatef Ben Jemaa; Chekib Mezigh; Benito Fraile; Nawfel Ben Rais; Ricardo Paniagua; Mar Royuela; Ridha Oueslati
In prostatism patients the ratio of human glandular kallikrein to free PSA improves the discrimination between prostate cancer and benign hyperplasia within the diagnostic “gray zone” of total PSA 4 to 10 ng\\/mL
Objectives. Human glandular kallikrein (hK2) possesses approximately 80% structure identity with prostate-specific antigen (PSA). Moreover, messenger ribonucleic acid for hK2 and for PSA is expressed in both benign and malignant prostatic tissue. We investigated whether the hK2 serum measurement may improve the detection of prostate cancer (PCa) in patients with total PSA of 4 to 10 ng\\/mL (diagnostic “gray zone”).Methods.
Maciej K Kwiatkowski; Franz Recker; Timo Piironen; Kim Pettersson; Thomas Otto; Martin Wernli; Reto Tscholl
ARLTS1 is a recently characterized tumor suppressor gene at 13q14.3, a region frequently deleted in both sporadic and hereditary prostate cancer (PCa). ARLTS1 variants, especially Cys148Arg (T442C), increase susceptibility to different cancers, including PCa. In this study the role of Cys148Arg substitution was investigated as a risk factor for PCa using both genetic and functional analysis. Cys148Arg genotypes and expression of the ARLTS1 were explored in a large set of familial and unselected PCa cases, clinical tumor samples, xenografts, prostate cancer cell lines and benign prostatic hyperplasia (BPH) samples. The frequency of the variant genotype CC was significantly higher in familial (OR?=?1.67, 95% CI?=?1.08–2.56, P?=?0.019) and unselected patients (OR?=?1.52, 95% CI?=?1.18–1.97, P?=?0.001) and the overall risk was increased (OR?=?1.54, 95% CI?=?1.20–1.98, P?=?0.0007). Additional analysis with clinicopathological data revealed an association with an aggressive disease (OR?=?1.28, 95% CI?=?1.05-?, P?=?0.02). The CC genotype of the Cys148Arg variant was also contributing to the lowered ARLTS1 expression status in lymphoblastoid cells from familial patients. In addition significantly lowered ARLTS1 expression was observed in clinical tumor samples compared to BPH samples (P?=?0.01). The ARLTS1 co-expression signature based on previously published microarray data was generated from 1587 cancer samples confirming the low expression of ARLTS1 in PCa and showed that ARLTS1 expression was strongly associated with immune processes. This study provides strong confirmation of the important role of ARLTS1 Cys148Arg variant as a contributor in PCa predisposition and a potential marker for aggressive disease outcome.
Schindler, Martin; Saramaki, Outi R.; Mpindi, John Patrick; Latonen, Leena; Vessella, Robert L.; Tammela, Teuvo L. J.; Kallioniemi, Olli; Visakorpi, Tapio; Schleutker, Johanna
This study aimed to evaluate the diagnostic and prognostic significance of serum bone sialoprotein (BSP) and prostate-specific antigen doubling time (PSADT) in patients with bone metastasis (BM) from prostate cancer (PC). A total of 116 patients with PC, 120 patients with benign prostatic hyperplasia (BPH) and 120 healthy controls were enrolled in this study. PC patients were divided into bone metastasis (BM) group (n=56) and non-bone metastasis (NBM) group (n=60). Serum BSP was detected by Sandwich ELISA. Severity of bone pain was evaluated using visual analogue score (VAS). Serum f-PSA and t-PSA levels were measured by using electrochemiluminescence immunoassay (ECLIA). PSADT was calculated according to the formula: PSADT=lg(2)/[log(PSA2)-log(PSA1)]. The mean serum BSP level in PC patients with BM was significantly higher than in PC patients without BM, BPH patients and controls (P<0.001 for all). Pearson's analysis showed that serum BSP level was positively correlated with VAS in PC patients with BM (P<0.05). Receiver operating characteristics (ROC) analysis demonstrated that BSP discriminated patients with BM from those without BM at the cutoff value of 33.26 ng/mL. The sensitivity and specificity were 78.21% and 79.28%, respectively. The optimal cutoff value of PSADT was 131 days, with sensitivity of 85.69% and specificity of 85.36%. Kaplan-Meier analysis revealed that subjects with higher BSP levels/shorter PSADT had a shorter BM-free period than those with lower BSP levels/longer PSADT. Serum BSP and PSADT are useful biomarkers for the diagnosis of BM from PC, and can be regarded as independent factors for predicting the prognosis of BM from PC. Combined determination of BSP and PSADT can improve accuracy and positive rate of BM from PC significantly. PMID:23904377
Wang, Yan; Zhang, Xiao-Fei; Dai, Ji; Zheng, Yong-Chi; Zhang, Ming-Gen; He, Jian-Jun
Emerging evidence has shown that the tumor microenvironment plays a crucial role in prostate cancer (PCa) development and progression. However, the mechanism(s) through which stromal cells regulate epithelial cells and the differences among prostatic stromal cells of different histological/pathological origin in PCa progression remain unclear. Therefore, it is necessary to characterize the stromal cell populations present in benign prostatic hyperplasia (BPH) and PCa. To this end, we used cultures from stromal cells obtained from BPH-derived (15 cases) and PCa-derived (30 cases) primary cultures. In culture, stromal cells are a mixture of fibroblasts, myofibroblasts (MFs) and muscle cells. Fibroblasts are characterized for the expression of vimentin, MFs for the co-expression of ?-smooth muscle actin (?-SMA) and vimentin, whereas muscle cells for the expression of ?-SMA and desmin. Fibroblasts were present in large amounts in the BPH- compared to the PCa-derived cultures, whereas MFs were more representative of PCa- as opposed to BPH-derived cultures. Some ?-SMA-positive cells retained the expression of basal cytokeratin K14. This population was defined as myoepithelial cells and was associated with senescent cultures. The percentage of MFs was higher in high-grade compared to moderate- and low-grade PCa-derived cultures, whereas the number of myoepithelial cells was lower in high-grade compared to moderate- and low-grade PCa-derived cultures. In addition, we analyzed the expression of p75NTR, as well as the expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of MMPs (TIMPs). p75NTR expression was elevated in the stromal cultures derived from PCa compared to those derived from BPH and in cultures derived from cases with Gleason scores ?7 compared to those derived from cases with Gleason scores <7, as well as in cultures with a high concentration of MFs compared to those with a high concentration of fibroblasts. MMP-2 was secreted by all primary cultures, whereas MMP-9 secretion was observed only in some PCa-derived stromal cells, when the percentage of MFs was significantly higher compared to BPH-derived cultures. TIMP1, TIMP2 and TIMP3 were secreted in elevated amounts in the BPH- compared to the PCa-derived stromal cultures, suggesting the differential regulation of extracellular matrix (ECM) degradation. When we used 22rv1 and PC3 PCa xenograft models for the isolation and characterization of murine cancer-associated fibroblasts (CAFs) we noted that the angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for ?-SMA, vimentin, tenascin, calponin, desmin and Masson's trichrome. In conclusion, MF stromal cells from PCa participate in the progression and metastasis of PCa, modualting inflammation, angiogenesis and epithelial cancer cell proliferation. PMID:23589051
Gravina, Giovanni Luca; Mancini, Andrea; Ranieri, Guido; Di Pasquale, Boris; Marampon, Francesco; Di Clemente, Luigi; Ricevuto, Enrico; Festuccia, Claudio
Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa) but has limited specificity for distinguishing early PCa from benign prostatic hyperplasia, because both PCa and benign prostatic hyperplasia release PSA into the serum. We have identified previously a truncated form of precursor PSA (pPSA) in prostate tumor extracts consisting of PSA with a serine-arginine pro leader
Stephen D. Mikolajczyk; Kathy M. Marker; Lisa S. Millar; Abhay Kumar; Mohammad S. Saedi; Janice K. Payne; Cindy L. Evans; Carlton L. Gasior; Harry J. Linton; Philip Carpenter; Harry G. Rittenhouse
Purpose To evaluate the serial changes in sexual function in the short-term period after holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia (BPH) and to investigate whether a change in each domain of the International Index of Erectile Function (IIEF) is associated with improvement of micturition. Materials and Methods Thirty-eight potent men who underwent HoLEP and in whom complete 12-month follow-up data on the IIEF were available were included in this retrospective study. All patients underwent a baseline evaluation for BPH. The surgical outcome was evaluated at 1, 3, 6, and 12 months postoperatively by use of the International Prostate Symptom Score, IIEF, and uroflowmetry. Results The mean age and body mass index of the patients was 64.5±6.2 years and 24.2±2.6 kg/m2, respectively. Mean total prostate volume and transitional zone volume were 48.8±18.8 ml and 24.2±16.1 ml, respectively. Most IIEF domain scores showed a slight decrease at 1, 3, and 6 months after surgery but recovered to the baseline or showed a marginal but nonsignificant increase at 12 months postoperatively compared with baseline. Orgasmic function and the overall sexual satisfaction domain score remained slightly reduced up to 12 months postoperatively. There was no significant correlation between improvement of micturition and change in sexual function throughout the follow-up period after surgery. Conclusions Although HoLEP achieves significant improvements in micturition, overall sexual function decreases slightly in the early postoperative period, but recovers to the baseline at 12 months postoperatively. Our data suggest that changes in sexual function after HoLEP are not associated with improvement of micturition.
Jeong, Min Su; Ha, Seung Beom; Lee, Chang Ju; Cho, Min Chul; Kim, Soo Woong
Prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) are the markers of human prostatic gland. However, it is still not completely understood if and how, steroid hormones and growth factors affect their expression and metabolism in the respect to the major pathologies of the gland. Appropriate studies were carried out on histopathologically diagnosed benign prostatic hyperplasia--BPH (n = 42) using tissue slices and cells derived from them. They were incubated with steroid hormones: 5-alpha-dihydrotestosterone (DHT), estradiol (E) and growth factors: epidermal growth factor (EGF), basic fibroblastic growth factor (bFGF) under culture conditions for up to 24 hours. P-labelled specific oligonucleotide probes were used to analyze total RNA isolated from each sample for the presence of PAP and PSA mRNAs. DHT, E, bFGF, EGF or both DHT + bFGF and DHT + EGF increased PAP and PSA mRNA levels in a time- and dose-dependent manner. The highest and statistically significant increase (P < 0.001) for PAP mRNA was observed when DHT + bFGF were present in the medium while for PSA mRNA if DHT + EGF were added to the medium. Slow but constant decrease of PAP and PSA mRNA levels was observed in the absence of each of these factors in the incubation medium. The results suggest that early expression of PSA and PAP genes and/or their mRNA stability strongly depend on DHT while differ in their response to EGF and bFGF. PMID:12362977
Duli?ska, Joanna; Laidler, Piotr; Labed?, Maria
The topic of this review is the role of stromal-epithelial interactions in normal and malignant prostatic growth. Because cell-cell interactions and androgens play such key roles in the prostate, the goal of this review will be to apply endocrinologic and developmental concepts to the understanding of normal and malignant prostatic growth. Prostatic development is induced by androgens, which act via androgen receptors. Androgens elicit prostatic epithelial growth during fetal and prepubertal periods, and in adulthood androgens act via reciprocal homeostatic stromal-epithelial interactions to maintain functional differentiation and growth quiescence. During carcinogenesis, these reciprocal homeostatic stromal-epithelial interactions are disrupted. In this review, 2 models of prostatic carcinogenesis will be reviewed, both of which emphasize the role of the stromal microenvironment in the carcinogenic process. Hormonal carcinogenesis of the prostate can be elicited by treatment of rats and mice with testosterone plus estradiol (T+E2). Using an immortalized but nontumorigenic human prostatic epithelial cell line (BPH-1), tissue recombinant studies were employed to explore the cellular mechanisms of prostatic carcinogenesis. Accordingly, human BPH-1 prostatic epithelial cells were combined with rat UGM, and the resultant UGM+BPH-1 recombinants were grown in adult male nude mouse hosts. In untreated mouse hosts, UGM+BPH-1 recombinants produced solid branched epithelial cords and ductal structures exhibiting benign growth. In T+E2-treated hosts, UGM+BPH-1 recombinants formed invasive carcinomas. Since BPH-1 cells lack androgen and estrogen receptors, whereas rat UGM expresses both of these receptors, it is proposed that hormonal carcinogenesis is elicited by T+E2 via paracrine mechanisms mediated by the stromal microenvironment. During prostatic carcinogenesis in rats and humans, the periepithelial stroma undergoes progressive loss in smooth muscle with the appearance of carcinoma-associated fibroblasts (CAFs). This abnormal stroma was shown to promote carcinogenesis in genetically abnormal but nontumorigenic epithelial cells. CAF+BPH-1 tissue recombinants grown in male hosts formed carcinomas, whereas benign growth and orderly tissue architecture developed in recombinants composed of normal prostatic stroma+BPH-1. Malignant transformation triggered by CAF was associated with additional genetic alterations and changes in gene expression in the BPH-1 cells. Thus, the stromal microenvironment is a critical determinant of benign versus malignant growth. PMID:12925950
Cunha, Gerald R; Hayward, Simon W; Wang, Y Z; Ricke, William A
Phosphodiesterase type 5 (PDE5) inhibitors have been demonstrated to improve lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). Because BPH is primarily driven by fibroblast-to-myofibroblast trans-differentiation, this study aimed to evaluate the potential of the PDE5 inhibitor vardenafil to inhibit and reverse trans-differentiation of primary human prostatic stromal cells (PrSC). Vardenafil, sodium nitroprusside, lentiviral-delivered short hairpin RNA-mediated PDE5 knockdown, sodium orthovanadate, and inhibitors of MAPK kinase, protein kinase G, Ras homolog family member (Rho) A, RhoA/Rho kinase, phosphatidylinositol 3 kinase and protein kinase B (AKT) were applied to PrSC treated with basic fibroblast growth factor (fibroblasts) or TGF?1 (myofibroblasts) in vitro, in chicken chorioallantoic membrane xenografts in vivo, and to prostatic organoids ex vivo. Fibroblast-to-myofibroblast trans-differentiation was monitored by smooth muscle cell actin and IGF binding protein 3 mRNA and protein levels. Vardenafil significantly attenuated TGF?1-induced PrSC trans-differentiation in vitro and in chorioallantoic membrane xenografts. Enhancement of nitric oxide/cyclic guanosine monophosphate signaling by vardenafil, sodium nitroprusside, or PDE5 knockdown reduced smooth muscle cell actin and IGF binding protein 3 mRNA and protein levels and restored fibroblast-like morphology in trans-differentiated myofibroblast. This reversal of trans-differentiation was not affected by MAPK kinase, protein kinase G, RhoA, or RhoA/Rho kinase inhibition, but vardenafil attenuated phospho-AKT levels in myofibroblasts. Consistently, phosphatidylinositol 3 kinase or AKT inhibition induced reversal of trans-differentiation, whereas the tyrosine phosphatase inhibitor sodium orthovanadate abrogated the effect of vardenafil. Treatment of prostatic organoids with vardenafil ex vivo reduced expression of myofibroblast markers, indicating reverse remodeling of stroma towards a desired higher fibroblast/myofibroblast ratio. Thus, enhancement of the nitric oxide/cyclic guanosine monophosphate signaling pathway by vardenafil attenuates and reverts fibroblast-to-myofibroblast trans-differentiation, hypothesizing that BPH patients might benefit from long-term therapy with PDE5 inhibitors. PMID:22948216
Zenzmaier, Christoph; Kern, Johann; Sampson, Natalie; Heitz, Martin; Plas, Eugen; Untergasser, Gerold; Berger, Peter
As a result of androgen ablation TGF-Beta expression levels transiently elevate and regression of benign prostate hyperplasia as well as prostate cancer cells for the most part occur. Better understanding of prostate- androgen responsiveness is critical i...
N. A. Bhowmick
The aim of this study was to evaluate the recurrence rate of simultaneous transurethral resection of bladder cancer and prostate (TURBT+TURP) in the treatment of non-muscle invasive bladder cancer (NMIBC) with benign prostatic hyperplasia (BPH). We searched PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ISI Web of Knowledge databases from their establishment until March 2012, to collect all the original studies on TURBT+TURP vs. TURBT alone in the treatment of NMIBC with BPH. After screening the literature, methodological quality assessment and data extraction was conducted independently by two reviewers and meta-analysis was performed using the RevMan 5.1 software. The quality of data was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Eight studies, including seven non-randomized concurrent controlled trials (NRCCTs) and one randomized controlled trial (RCT), involving a total of 1,372 patients met the criteria. Meta-analyses of NRCCTs showed that in the TURBT+TURP group, overall recurrence rates were lower [odds ratio (OR), 0.76; 95% confidence interval (CI), 0.60–0.96; P=0.02] and the difference was statistically significant. The postoperative recurrence rate in the prostatic fossa/bladder neck (OR, 0.96; 95% CI, 0.64–1.45; P=0.86) and bladder tumor progression rates (OR, 0.96; 95% CI, 0.49–1.87; P=0.91) were similar between the TURBT+TURP and TURBT groups, but the difference was not significant. According to the GRADE approach, the level of evidence was moderate or low. Only one RCT demonstrated that overall postoperative tumor recurrence rates, recurrence rates at prostate fossa/bladder neck and bladder tumor progression rates between simultaneous groups and control groups were almost equal. There was no significant difference (P>0.05), and the level of evidence was moderate. For patients with NMIBC and BPH, simultaneous resection did not increase the overall recurrence rate of bladder tumors, it also did not cause metastasis and tumor progression, but it may reduce the recurrence rate. However, due to the low quality of investigations included in the present study, careful selection was necessary, and more large-scale and high-quality randomized controlled trials are also required for further confirmation.
LI, SHENG; ZENG, XIAN-TAO; RUAN, XIAO-LAN; WANG, XING-HUAN; GUO, YI; YANG, ZHONG-HUA
Benign prostatic hypertrophy (BPH) is a common condition in elderly men that impairs quality of life and leads to a number of medical complications. The use of phytotherapeutic compounds in patients with relatively moderate BPH symptoms has been growing steadily. In the present study, acute toxicity of lyophilised aqueous extracts of Cistus incanus L. and Cistus monspeliensis L., collected in
Federica Vitali; Giuseppa Pennisi; Giuseppa Attaguile; Francesca Savoca; Beatrice Tita
Objectives:This retrospective analysis evaluated the efficiency, safety, and medium term postoperative results of bipolar plasma vaporization (BPV) in prostate cancer (PCa) cases associating complete urinary retention. Materials and Methods: A series of 40 patients diagnosed with locally advanced or metastatic PCa and complete urinary retention requiring a Foley catheter indwelling underwent BPV aiming to restore spontaneous voiding. A total of 35 patients completed the one year evaluation protocol consisting of International Prostate Symptom Score (IPSS), quality of life score (QoL), maximum flow rate (Qmax) and post-voiding residual urinary volume (PVR), measured at 1, 3, 6 and 12 months after surgery. Results: BPV was successfully performed in all cases with satisfactory efficiency, as confirmed by the mean operation time (42.8 minutes) and hemoglobin drop (0.7 g/dl). A fast and safe postoperative recovery period was described in this series (hematuria rate – 7.5%; mean catheterization period – 36 hours; mean hospital stay – 2.5 days; early-irritative symptoms’ rate – 15%). At 1, 3, 6 and 12 months, satisfactory values were determined in terms of IPSS, Qmax, QoL and PVR. These parameters emphasized a stable evolution throughout the entire follow-up, as 88.6% of the patients maintained spontaneous voiding. Conclusions: The present trial confirmed the plasma-button vaporization as a promising therapeutic approach in PCa cases associating complete urinary retention. The technique displayed good efficacy, low perioperative morbidity, short convalescence, and satisfactory urodynamics and symptom score parameters during the one-year follow-up period. Abbreviations: BPV – bipolar plasma vaporization; PCa – prostate cancer; TURP – transurethral resection of the prostate; BPH – benign prostatic hyperplasia; BOO – bladder outlet obstruction; LUTS – lower urinary tract symptoms; IPSS – International Prostate Symptom Score; QoL – quality of life score; Qmax – maximum flow rate; RV – post-voiding residual urinary volume
Geavlete, B; Moldoveanu, C; Nita, G; Stanescu, F; Jecu, M; Geavlete, P
The study was designed to investigate the effect of serum glucose, insulin and insulin resistance on the risk of prostate cancer (CaP) and on the clinicopathological characteristics in Korean men. Subjects were retrospectively recruited from 166 CaP patients underwent radical prostatectomy and 166 age-matched benign prostatic hyperplasia (BPH) patients. The serum was taken on the morning of the day of operation and insulin resistance was assessed by homeostasis model assessment insulin resistance index (HOMA-IR). Men in highest tertile of insulin was associated with 55% reduced odds of CaP than those with the lowest tertile (OR = 0.45, 95% CI = 0.23-0.89, P = 0.022). The patients in highest tertile of insulin had a more than 5.6 fold risk of locally advanced stage than those in the lowest tertile (OR = 5.62, 95% CI = 1.88-16.83, P = 0.002). Moreover, the patients in the highest tertile HOMA-IR group was associated with an increased risk of locally advanced stage than the lowest tertile group (OR = 3.10, 95% CI = 1.07-8.99, P = 0.037). These results suggest that elevated insulin and insulin resistance are associated with the advanced pathological stage of prostate cancer in Korean patients.
Yun, Seok Joong; Min, Byung-Dal; Kang, Ho-Won; Shin, Kyung-Sub; Kim, Tae-Hwan; Kim, Won-Tae; Lee, Sang Cheol
Background: Sexual function has been detected in a large sample of Italian patients affected by LUTS suggestive of BPH, by means of the ICS-Sex questionnaire. Results: A number of 877 questionnaires were returned completely filled and were analyzed. Fifty percent of patients declared that their sexual life was significantly affected by their urinary symptoms. Difficulty in getting erections (58.2% of
Andrea Tubaro; Massimo Polito; Lucilla Giambroni; Ciro Famulari; Ercole Gange; Edoardo Ostardo
Purpose The objectives of this study were to evaluate whether morphologic differences correlated with urodynamic and clinical characteristics in patients with benign prostatic hyperplasia (BPH) with intravesical prostatic protrusion (IPP) of trilobar or bilobar adenoma. Materials and Methods Between January 2008 and June 2009, 72 male patients who had undergone transurethral resection (TUR) owing to BPH with IPP were included in this study. They underwent preoperative urodynamic studies, the International Prostate Symptom Score (IPSS)/quality of life (QoL), maximal flow rate (Qmax), post-voiding residual urine volume (PVR), transrectal ultrasonography (TRUS), and serum prostate-specific antigen (PSA) measurement. The patients were classified into 2 groups (the trilobar and bilobar adenoma groups) on the basis of video findings during the TUR operation. Results The trilobar and bilobar adenoma groups consisted of 37 patients and 35 patients, respectively. The Mean±SD IPP, prostate volume (PV), and transition zone volume of the trilobar and bilobar adenoma groups were 11.8±5.2 mm and 9.0±3.8 mm (p=0.014), 81.1±25.8 g and 59.3±22.5 g (p<0.001), and 49.6±20.6 g and 34.8±19.4 g (p=0.003), respectively. The Mean±SD PSA, bladder contractility index (BCI), and bladder outlet obstruction index (BOOI) were 4.6±2.5 ng/ml and 3.5±1.7 ng/ml (p=0.042), 119.8±33.4 and 87.7±24.4 (p<0.001), and 62.6±29.5 and 44.6±20.4 (p=0.005), respectively. There were no significant differences in IPSS/QoL, Qmax, PVR, acute urinary retention, or detrusor overactivity in the 2 groups. Conclusions IPP has two morphologic types of trilobar or bilobar enlargement. The PV, BOOI, and BCI were significantly smaller in the bilobar adenoma group than in the trilobar adenoma group.
Lee, Seung Wook; Cho, Jeong Man; Kang, Jung Yoon
We conducted an expression analysis of prostate stem cell antigen (PSCA) in normal urogenital tissues, benign prostatic hyperplasia (n 21), prostatic intraepithelial neoplasia ( n 33), and primary (n 137) and metastatic (n 42) prostate adenocarcinoma, using isotopic in situ hybridization on tissue microarrays. In normal prostate, we ob- serve PSCA expression in the terminally differentiated, secretory epithe- lium; strong
Sarajane Ross; Susan D. Spencer; Ilona Holcomb; Christine Tan; JoAnne Hongo; Brigitte Devaux; Linda Rangell; Gilbert A. Keller; Peter Schow; Rita M. Steeves; Robert J. Lutz; Gretchen Frantz; Kenneth Hillan; Franklin Peale; Patti Tobin; David Eberhard; Mark A. Rubin; Laurence A. Lasky; Hartmut Koeppen
The RNASEL gene (2?,5?-oligoisoadenylate-synthetase dependent) encodes a ribonuclease that mediates the antiviral and apoptotic activities of interferons. The RNASEL gene maps to the hereditary-prostate-cancer (HPC)–predisposition locus at 1q24-q25 (HPC1) and was recently shown to harbor truncating mutations in two families with linkage to HPC1. Here, we screened for RNASEL germline mutations in 66 Finnish patients with HPC, and we determined the frequency of the changes in the index patients from 116 families with HPC, in 492 patients with unselected prostate cancer (PRCA), in 223 patients with benign prostatic hyperplasia (BPH), and in 566 controls. A truncating mutation, E265X, was found in 5 (4.3%) of the 116 patients from families with HPC. This was significantly higher (odds ratio [OR]=4.56; P=.04) than the frequency of E265X in controls (1.8%). The highest mutation frequency (9.5%) was found in patients from families with four or more affected members. Possible segregation was detected only in a single family. However, the median age at disease onset for E265X carriers was 11 years less than that for noncarriers in the same families. In addition, of the four missense variants found, R462Q showed an association with HPC (OR=1.96; P=.07). None of the variants showed any differences between controls and either patients with BPH or patients with PRCA. We conclude that, although RNASEL mutations do not explain disease segregation in Finnish families with HPC, the variants are enriched in families with HPC that include more than two affected members and may also be associated with the age at disease onset. This suggests a possible modifying role in cancer predisposition. The impact that the RNASEL sequence variants have on PRCA burden at the population level seems small but deserves further study.
Rokman, Annika; Ikonen, Tarja; Seppala, Eija H.; Nupponen, Nina; Autio, Ville; Mononen, Nina; Bailey-Wilson, Joan; Trent, Jeffrey; Carpten, John; Matikainen, Mika P.; Koivisto, Pasi A.; Tammela, Teuvo L. J.; Kallioniemi, Olli-P.; Schleutker, Johanna
It is well known that prostate cancer (PCa) occurs predominantly in the peripheral zone (PZ), whereas benign prostatic hyperplasia (BPH) typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone (PZsc) and the transition zone (TZsc) on a PCa epithelial cell line (PC3) in the presence of sex hormones. First, we observed that androgen receptor (AR) mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone (DHT) and ?-oestradiol (E2) (P<0.05). By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor (KGF) secretion increased with increasing concentrations of DHT (P<0.01) and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-?1 (TGF-?1) than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 (IGF-1) secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmol l?1 DHT plus 10 nmol l?1 E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa.
Jiang, Qi; Han, Bang-Min; Zhao, Fu-Jun; Hong, Yan; Xia, Shu-Jie
The present study explores the mechanisms by which human prostatic carcinoma-associated fibroblasts (CAF) induce tu- morigenesis in initiated but nonmalignant human prostatic epithelial cells (BPH-1). CAF express elevated levels of both transforming growth factor-B1(TGF- B1) and stromal cell- derived factor-1 (SDF-1\\/CXCL12). TGF-B inhibits the growth of BPH-1cells in vitro, but was found to be necessary for the tumorigenic response to
Mingfang Ao; Omar E. Franco; Dayanidhi Raman; Karin Williams; Simon W. Hayward
Background As a significant overlap of 11C-Choline standardized uptake value (SUV) between prostate cancer and benign prostate hyperplasia (BPH) tissue, controversy exists regarding the clinical value of 11C-Choline PET/CT scan in primary prostate cancer. In this study, the SUVmax of the prostate lesions and the pelvic muscles were measured and their ratios (SUVmax-P/M ratio) were calculated. Then we evaluated whether the tracer 11C-Choline uptake, quantified as SUVmax-P/M ratio, correlated with tumour stage, Gleason score, and expression levels of several biomarkers of aggressiveness. Methods Twenty-six patients with primary prostate cancer underwent 11C-Choline PET/CT. Tumour specimens from these patients were graded histopathologically, and immunnohistochemistry for Ki-67, CD31, androgen receptor (AR), Her-2/neu, Bcl-2, and PTEN were performed. Results Both SUVmax and SUVmax-P/M ratio showed no significant difference between patients with tumour stage II and III, but significantly elevated in patients with tumour stage IV. SUVmax-P/M ratio was also significantly higher in lesions with Gleason score of 4+3 or higher versus less than or equal to 3+4. SUVmax-P/M ratio was found significantly correlated with expression levels of Ki-67 and CD31. In addition, a higher SUVmax-P/M ratio was demonstrated in Her-2/neu positive subgroup than negative subgroup. At the same time, Gleason score and expression levels of these biomarkers showed no significant association with SUVmax. Conclusions Using the parameter SUVmax-P/M ratio, 11C-Choline PET/CT may be a valuable non-invasive imaging technology in the diagnosis of primary prostate cancer.
Chen, Ji; Zhao, Yong; Li, Xin; Sun, Peng; Wang, Muwen; Wang, Ridong; Jin, Xunbo