Both Benign Prostatic Hyperplasia Research Articles

The causal relationship between sarcopenic obesity factors and benign prostate hyperplasia.

Both benign prostatic hyperplasia (BPH) and sarcopenic obesity (SO) are common conditions among older adult/adults males. The prevalent lifestyle associated with SO is a significant risk factor for the development of BPH. Therefore, we investigated the causal relationship between SO factors and BPH. The instrumental variables for SO factors were selected using the inverse variance-weighted method, which served as the primary approach for Mendelian randomization analysis to assess the causal effect based on summary data derived from genome-wide association studies of BPH. The increase in BMR (OR = 1.248; 95% CI = (1.087, 1.432); P = 0.002) and ALM (OR = 1.126; 95% CI = (1.032, 1.228); P = 0.008) was found to be associated with an elevated risk of BPH. However, no genetic causality between fat-free mass distribution, muscle mass distribution, and BPH was observed. Our findings indicate that a genetic causal association between BMR, ALM and BPH. BMR and ALM are risk factors for BPH. The decrease in BMR and ALM signified the onset and progression of SO, thus SO is a protective factor for BPH.

CD44 rs13347C>T Variants in 3'UTR and Prostate Neoplasms: A Case-control Study and Bioinformatics Approach.

CD44, a cell-surface receptor and a key player in cellular signaling, can act as both tumor suppressor and promoter. This study aimed to investigate the association of CD44 rs13347C>T variants with prostate neoplasms, including both benign prostatic hyperplasia (BPH) and prostate cancers using a case-control and bioinformatics approach. Genomic DNA was extracted from 545 blood samples (225 BPH, 225 prostate cancers, and 95 control) and the CD44 rs13347C>T genotypes were identified using PCR-RFLP. We explored miRNA interactions using the miRNASNP-v3 database and GeneMANIA for co-expression networks. Results showed cancer patients had significantly higher PSA levels compared to both controls (p= 0.03) and BPH (p= 0.01). Additionally, digital rectal examination-positive and smoker BPH patients showed significantly the increased cancer risk (p= 0.004, p= 0.046). Prostate cancer group indicated significantly higher frequency of CD44 rs13347C>T mutant allele compared to control and BPH groups, particularly in TT and CT+TT genotypes (p < 0.05). miRNA SNP-v3 database predicted the mutant allele of CD44 rs13347C>T could lose 1 and gain 6 miRNAs for a new site created. Co-expression analysis revealed a direct interaction between CD44 and aryl hydrocarbon receptor (AHR), a gene known to be dysregulated in smokers. Furthermore, these genes alone display co-expression interactions with integrin subunit alpha 4 (ITGA4), protein plays a paradoxical role, both suppressing and promoting tumors. Based on the findings, the mutant allele of CD44 rs13347C>T may disrupt miRNA binding, which may potentially impact CD44, AHR, and ITGA4 expression in smokers, possibly contributing to prostate cancer progression.

Applications of Vertebrate Models in Studying Prostatitis and Inflammation-Associated Prostatic Diseases.

It has long been postulated that the inflammatory environment favors cell proliferation, and is conducive to diseases such as cancer. In the prostate gland, clinical data implicate important roles of prostatitis in the progression of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). However, their causal relationships have not been firmly established yet due to unresolved molecular and cellular mechanisms. By accurately mimicking human disease, vertebrate animals provide essential in vivo models to address this question. Here, we review the vertebrate prostatitis models that have been developed and discuss how they may reveal possible mechanisms by which prostate inflammation promotes BPH and PCa. Recent studies, particularly those involving genetically engineered mouse models (GEMMs), suggest that such mechanisms are multifaceted, which include epithelium barrier disruption, DNA damage and cell proliferation induced by paracrine signals, and expansion of potential cells of origin for cancer. Future research using rodent prostatitis models should aim to distinguish the etiologies of BPH and PCa, and facilitate the development of novel clinical approaches for prostatic disease prevention.

Dihydrotestosterone and Free/Total Prostatic Specific Antigen Ratio in Diagnosis and Prognosis of Prostatic Disease

Background: Both benign prostatic hyperplasia (BPH) and prostate cancer (Pca) include prostate enlargement. The second most common cancer among men worldwide is prostate cancer. It has been documented that by the time they reach their 60s, most men will experience benign prostatic hyperplasia. There is a real difficulty differentiating between benign prostatic hyperplasia and prostate cancer, the prostatic specific antigen (PSA) is not used as a reliable marker of prostate cancer. It is a specific biomarker measure specific to prostate tissues and not prostate cancer. Aims In the analysis of the gray zone of tPSA (4-10 ng/ml), add these biochemical markers and differentiate the root cause of prostate tumor in order to minimize painful and intrusive prostate biopsy. Materials and Methods: A cross-sectional and case control study. It included 110 patients ages range (45-81 years) with benign prostatic hyperplasia (n=55) and prostate cancer (n=55). Forty -five apparently healthy subjects were also included as controls. Peripheral blood samples from controls and patients were collected before obtaining a prostatic biopsy from patients. Serum samples were used for measurements of total Prostate Specific Antigen (tPSA), Free Prostate Specific Antigen (fPSA), and Dihydrotestosterone (DHT) by using ELISA technique. Result: Mean (±SD) serum tPSA and fPSA values for Pca were substantially improved compared to both BPH and control (p=0.001 for all), while mean fPSA/tPSA values for PCa were significantly decreased compared to BPH and control values (p=0.001). In PCa, the mean +SD value of the DHT ratios was significantly lower than in each BHP, and controls (P&lt;0.001) were significantly lower in PCa than in each BHP and regulation (P&lt;0.001). The mean DHT values for BPH were significantly higher as compared to control values (p&lt; 0.001). Conclusion: The level of serum tPSA is 4.2 ng/ml for prostate tumor screening, while 10.1 ng/ml for PCa and BPH differentiation.

Assessment of Learning Curves for 180-W GreenLight XPS Photoselective Vaporisation of the Prostate: A Multicentre Study

BackgroundThe learning curve for photoselective vaporisation of the prostate (PVP) has never been assessed accurately. ObjectiveTo compare 180-W GreenLight XPS PVP learning curves for three surgeons with different levels of surgical experience and different institutional backgrounds. Design, setting, and participantsA multicentre retrospective study of the first patients treated with PVP by three operators in three different centres (n=152 in group 1, n=112 in group 2, n=101 in group 3) was conducted. Surgeon 1 had performed >600 PVP procedures (120-W GreenLight HPS laser) since 2007, while surgeons 2 and 3 had no previous experience with GreenLight PVP. Surgeon 1 mainly treats both benign prostatic hyperplasia (BPH) and urologic oncology, surgeon 2 primarily focuses on urologic oncology, and surgeon 3 mostly treats BPH. Surgeon experience was analysed as a continuous variable in terms of consecutive procedures performed. InterventionPVP using a 180-W GreenLight XPS laser. Outcome measurements and statistical analysisThe learning curve was analysed in terms of changes over time for the following variables: operative time, the vaporisation time/operative time ratio, and the energy delivered/prostate volume ratio. The primary endpoint was a trifecta of (1) energy delivered >5kJ/ml of prostate, (2) vaporisation time/operative time ratio of 66–80%, and (3) no postoperative complications. Results and limitationsPatient baseline characteristics differed significantly among the centres in terms of age, prostate volume, and International Prostate Symptom Score (IPSS). Most perioperative outcomes favoured group 1 over group 3 over group 2. Functional outcomes, such as a decrease in IPSS at 1 mo for the first 50 patients (−15 vs −13.6 vs −13.3; p<0.0001) and an increase in maximum flow at 1 mo for the first 50 patients (+14.2 vs. +7 vs. +9.4; p<0.0001), favoured group 1 over group 3 over group 2. The trifecta achievement rate was significantly higher in group 3 over group 1 over group 2 (26.7% vs 14.4% vs 5.4%; p<0.0001). In multivariate analysis adjusting for age, American Society of Anesthesiologists score, and preoperative prostate volume, the only factors predictive of trifecta achievement were surgeon experience (p<0.0001) and surgeon identity (p<0.0001). The study limitations include selection bias, short follow-up, and a lack of consensus regarding learning curve assessment and definition. ConclusionsMore than 100 PVP procedures were required to reach an intraoperative parameter plateau regardless of surgeon expertise and institutional background. Both surgeon background and expertise seemed to influence perioperative outcomes during the GreenLight XPS PVP learning curve. Patient summaryBoth surgeon background and expertise seem to influence perioperative outcomes during the learning curve when using a GreenLight XPS laser for photoselective vaporisation of the prostate.

Can cyclin D1 be utilized as a second step &amp;#147;after basal cell marker&amp;#148; for both diagnosis and prognosis of prostatic adenocarcinoma?

Background: Cyclin D1 is involved in regulating cell cycle as well as cancer progression and its overexpression is incriminated in the pathogenesis of many tumors including prostatic adenocarcinoma (PAC). One of the basal cell markers is p63. p63 is a nuclear protein, which plays a critical role in the growth and development of many epithelial organs. p63 is confined to basal cells of squamous epithelia and urothelium, as well as basal cells of many organs including, prostate. So, confirmation of the presence or absence of basal cell layer is the first clue to deny or ascertain the diagnosis of PAC. Objective: To investigate the expression of cyclin D1 with p63 in both benign prostatic hyperplasia (BPH) and PAC and correlate the results of cyclin D1 with both Gleason ‘s score and clinical staging. Materials and Methods: Retrospective evaluation of archived specimens of BPH and PAC and p63 was used for more confirmation of the histopathological state. This study was done in 60 cases of BPH and 60 cases of PAC. All cases were stained for p63 before staining with cyclin D1 antibody. All immunohistochemical analyses were performed on routinely processed, formalin-fixed, paraffin-embedded tissue. Any degree of reactivity was considered positive. Percentage of positive cells was calculated and scored as follows: + (weak) = less than 10%, ++ (moderate) = 11% to 50%, and +++ (strong) = more than 50% tumor cells stained positive. Immunohistochemical expressions were correlated with Gleason grade as well as staging of PAC in an attempt to recognize the prognostic value of cyclin D1. Result: Cyclin D1 was expressed in 13% and 93% of BPH and PAC cases, respectively, opposite to 92% and 4% in that of p63. In PAC cases, the degree of cyclin D1 reactivity was increased in high Gleason’s grade with significant correlation (P = 0.043). Also a significant correlation was obtained between the degree of staining and the staging of PAC (P = 0.045). Conclusion: Cyclin D1 is highly expressed in PAC cases and its overexpression was seen in high Gleason’s score and staging beyond T2.

Benign prostatic hyperplasia complicated with T1DM can be alleviated by treadmill exercise-evidences revealed by the rat model.

BackgroundBoth benign prostatic hyperplasia (BPH) and Type-1 diabetes mellitus (T1DM) share similar epidemiologic features and are all associated with the insulin-like growth factor (IGF)-mediated hormonal imbalance. The purpose of this study is to understand whether exercise (EX) could alleviate DM and DM + BPH.MethodsSprague-Dawley rats were divided into eight groups: normal control, EX, BPH, BPH + EX, DM, DM + EX, BPH + DM, and BPH + DM + EX. T1DM was induced by intraperitoneal (ip) injection of streptozotocin (65 mg/kg) in Week 2, and BPH was induced by successive ip injections of Sustanon® (testosterone, 3.5 mg/head) plus estradiol (0.1 mg/head) from Week 3 to Week 9. Treadmill exercise training (20 m/min, 60 min per time) was performed three times per week for 6 weeks.ResultsIn BPH + EX, EX maintained at a constant body weight (BW); and suppressed stromal layer thickening, collagen deposition, blood glucose (BG), levels of testosterone (Ts), 5α-reductase(5αRd), dihydrotestosterone (DHT), androgen receptor (AR), serum hydrogen peroxide, TBARs, and interleukin-6 (IL-6). EX recovered testes size and substantially increased nitric oxide (NO) levels. In DM + EX group, EX decreased BW, PW, nuclear proliferation, inflammatory cell aggregation, collagen deposition, and BG. As contrast, EX upregulated insulin, IGF, Ts, NO, 5αRd, AR, and DHT, and substantially reduced PSA. In BPH + DM + EX, EX maintained BW at a subnormal level, slightly suppressed prostate stromal inflammation, collagen deposition, and BG, moderately restored sIn and IGF. Although failed to suppress Ts, EX highly upregulated 5αRd and suppressed DHT and AR, together with highly upregulated NO resulting in substantially reduced PSA.ConclusionEX, by remodeling androgen and NO expressions, can effectively alleviate BPH, DM, and BPH + DM.

Prostatic diseases under focus in a university hospital in Eastern Saudi Arabia. A 15-year experience.

Objectives:To explore the spectrum of pathologies diagnosed in prostatic biopsies of Saudi men, and test whether the frequency of diagnosing the malignant fraction has been changed over the last 15 years, and assess the association between chronic inflammation (CI) with both benign prostatic hyperplasia (BPH) and cancer (PCa), and investigate the histological findings of cases presented with acute urinary retention (AUR) clinically.Methods:This is a retrospective cohort study including all prostatic biopsies accessed in the files in the Surgical Pathology Laboratory of King Fahd University Hospital, Alkhobar, Kingdom of Saudi Arabia over 15 years (1999-2013) for Saudi men. Age, procedure indication, and final diagnoses were retrieved and slides were reviewed.Results:There were 360 cases included in this study with a median age of 65 year-old. The BPH comprised the most (64.7%), while PCa accounted for 89 cases, 13.5% of which were incidental. Most cases of both BPH and PCa were diagnosed in the seventh decade. The frequency of diagnosing PCa did not show a solid rise or fall over time. Chronic inflammation is more related to BPH than to PCa. Only CI showed a significant statistical association with AUR.Conclusion:Prostatic diseases show a stable trend over time. While CI is a common dominator for both BPH and PCa, it is associated more with BPH. Among all histological findings, only CI is related to the clinical presentation of AUR.

Molecular Evidence of Helicobacter Pylori Infection in Prostate Tumors

Objectives: To determine whether Helicobacter pylori (H. pylori) is detectable in both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Epidemiological studies have shown significant associations between infective chronic prostatitis and prostatic carcinoma. Many bacteria have been found in the prostate of patients with chronic prostatitis, BPH, and PCa. Methods: One hundred consecutive patients with prostate diseases were enrolled in the study. Detection of H. pylori DNA in prostate tissue from patients with BPH and PCa was performed using both immunohistochemistry and PCR, and the results were confirmed by DNA sequencing. Odds ratios and the Fisher Exact test were used for the analysis of the associations between the variables. Results: Among the patients, 78% had BPH and 19% had PCa. While immunohistochemistry showed no positive sample for H. pylori, PCR combined with sequencing detected H. pylori DNA in prostate tissue samples from 5 patients. However, statistical analysis of the data showed that BPH and PCa are not significantly associated with the presence of H. pylori DNA in prostate tissue (odds ratio = 0.94, 95% confidence interval = 0.09-23.34, one-tailed Chi-square value = 0.660, p > 0.05). The limitation of this study was the small number of PCa patients. Conclusions: This study provides, for the first time, molecular evidence of the presence of H. pylori DNA in prostatic tissue of patients with BPH and PCa. It paves the way for further comprehensive studies to examine the association of H. pylori infection with BPH and PCa.

Role of once-daily tadalafil in men with concomitant erectile dysfunction and symptomatic benign prostatic hyperplasia: A prospective randomized placebo-controlled study

Background: Majority of men over age 50 are sexually active and sex is an important part of overall quality of life. Both benign prostatic hyperplasia (BPH) with lower urinary tract symptoms-BPH (BPH-LUTS) and erectile dysfunction (ED) are often found in this age group simultaneously. Pathophysiological mechanisms for both these diseases are almost common. All males presenting with LUTS should be assessed for sexual dysfunction and viceversa. The aim of this study is to evaluate the effects of once-daily tadalafil on erectile function in men with ED and benign prostatic hypertrophy with LUTS. One drug for treatment of both diseases and better patient's compliance are important issues for proper management. Materials and Methods: We did a study of 60 men. All patients were divided in two groups: 30 in group A who were given tadalafil 5 mg (megalis-5 mg of Macleods Pharmaceutical Company) and 30 patients in group B who were on placebo (plain sugar pills) for 12-week. This was a randomized, placebo-controlled study of once-daily tadalafil, which was carried out in men with BPH-LUTS in a rural Medical College of Northern India during June 2009 to November 2011. Results: International index of erectile function-erectile function (IIEF-EF) domain score improvements from baseline with 5 mg once-daily tadalafil were significantly greater throughout the study for tadalafil groups versus placebo (all P ≤ 0.001). International Prostate Symptom Score (IPSS) improvements from baseline to end point were significantly greater with 5 mg tadalafil dose versus placebo (all P Conclusion: There are encouraging results with tadalafil. It was used in 30 patients who were suffering with both ailments of BPH and LUTS simultaneously and is effective in both diseases.

Androgen receptor and immune inflammation in benign prostatic hyperplasia and prostate cancer

Both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are frequent diseases in middle-aged to elderly men worldwide. While both diseases are linked to abnormal growth of the prostate, the epidemiological and pathological features of these two prostate diseases are different. BPH nodules typically arise from the transitional zone, and, in contrast, PCa arises from the peripheral zone. Androgen deprivation therapy alone may not be sufficient to cure these two prostatic diseases due to its undesirable side effects. The alteration of androgen receptor-mediated inflammatory signals from infiltrating immune cells and prostate stromal/epithelial cells may play key roles in those unwanted events. Herein, this review will focus on the roles of androgen/androgen receptor signals in the inflammation-induced progression of BPH and PCa.

Fireweed – a treasured medicine of the boreal forest

A large segment of the Canadian population (approximately 71%) take natural health products, The Baseline Natural Health Products Survey among Consumers, suggesting this trend is likely to continue, with increasing awareness of side effects associated with pharmaceutical prescriptions and over the counter medications. Fireweed (Chamerion angustifolium) is an often-overlooked herb with amazing medicinal properties. Traditional First Nations usage and modern pharmacology as well as clinical studies suggest its beneficial effects in a number of health concerns. Fireweed has been known to possess anti-inflammatory effects in addition to the recent evidence on its therapeutic effects for both benign prostatic hyperplasia (BPH), and prevention of prostate cancers. This mini review provides some additional information obtained from First Nations healers, the empirical knowledge associated with clinical practice and aims to stimulate additional interest in the genus, and especially in the circumpolar species of Chamerion angustifolium.

The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme?

Normal growth and function of the prostate are contingent on the reduction of testosterone to dihydrotestosterone (DHT) by 5-alpha reductase (5-AR) enzymes types 1 and 2. It has been theorized that an overabundance of DHT may be implicated in the pathogenesis of both benign prostatic hyperplasia (BPH) and prostate cancer. Inhibitors of 5-AR such as dutasteride and finasteride may therefore have an important role in the prevention and treatment of BPH and prostate cancer. Dutasteride provides greater suppression of DHT than finasteride, thereby underlying the hypothesis that inhibition of both type 1 and type 2 would provide correspondingly greater protection than inhibition of type 2 alone. We review the potential significance of the 5-AR inhibitors in reducing the risk of prostate cancer according to the basic biology of prostate disease.

Major role for 5-alpha reductase inhibitors in the aging male

The Canadian consensus meeting, held in Toronto in May 2006, represents an important initiative in sorting out much of the confusion surrounding the use of 5-alpha reductase inhibitors (5ARIs) in clinical practice. The impact of the Medical Therapy of Prostatic Symptoms study and the Prostate Cancer Prevention Trial (PCPT) are quite dramatic as they confirm that 5ARIs, a class of drugs that never gained much market share in urologic practice, have significant impact on both benign prostatic hyperplasia (BPH) and prostate cancer- related outcomes. It is quite ironic that these pivotal trials, funded not by industry but by tax payers, have come to fruition at a time when finasteride is soon to be genericized in the United States. Commercial interests aside, this consensus summary provides useful information for urologists and primary care physicians. With respect to BPH-related outcomes, the 5ARIs have clearly demonstrable benefits in reducing long-term complications and lower urinary tract symptoms (LUTS). There is little debate on this topic. The impact of 5ARIs on prostate cancer prevention remains controversial and, in my mind, these recommendations have some limitations that deserve mention. With respect to the grade and volume bias, this observation, internationally led by our group, is real, and many other centres are now reporting it. We must emphasize that these recommendations report that this bias explains the PCPT grade issue “with a high degree of confidence.” While I truly believe this is the case, a small but lingering doubt must still exist within us all. It is essentially now unprovable! Perhaps more relevant than the grade issue is the clinical significance of the prevented cancers. Indeed, in the PCPT the relative risk reduction in “for-cause” biopsies, those that mirror clinical practice, is only 10%. I believe that future pivotal trials, such as REDUCE (the Reduction by Dutasteride of Prostate Cancer Events study; dutasteride v. placebo among men with negative prostate biopsy and elevated prostate-specific antigen), will help us clarify some of these issues. With respect to class effect and use of 5ARIs, I believe that both 5ARIs are good agents and that there are theoretical advantages to dutasteride in cancer prevention. Further trials will bear this out. What are clinicians to do? Consider the cancer prevention properties as an added benefit to complication reduction and symptom improvement for men with large-volume BPH and LUTS. In my view, either 5ARI is appropriate. Consider primary prevention with 5-ARI in ultra-high risk men, those in whom a cancer is likely to be clinically significant (e.g., men with strong family history, African-Canadians or both). In this setting, the best evidence would support the use of finasteride.

Regarding prostate-specific antigen: let's not shoot the messenger

It is well known that androgens drive prostate cancer and the inhibition of 5α-reductase results in an inhibition of the conversion of testosterone to dihydrotestosterone, the active androgen in the prostate. Recently, two large prospective randomized trials have tested the 5α-reductase inhibitors, finasteride1 and dutasteride2 compared to placebo for the chemoprevention of prostate cancer in middle aged and elderly men. Both trials demonstrated that 5α-reductase inhibitor therapy significantly decreased subsequent low-grade (Gleason score ≤ 6) prostate cancers, however, high-grade (Gleason score 8–10) prostate cancers were significantly increased by nearly 2-fold.3 Stated otherwise, therapy with a 5α-reductase inhibitor to prevent prostate cancer resulted in one additional high-grade cancer as a trade-off to avoid four low-grade cancers.3 Although these findings have been vigorously debated, there has been no definitive explanation why they should be discounted, and they have come under intense scrutiny by the US Food and Drug Administration.3 Additionally, these findings should not be surprising since it was previously shown that the treatment of men with finasteride who have high-grade prostatic intraepithelial neoplasia (PIN), a common precursor lesion of prostate cancer, results in a significant increase in prostate cancer by 1 year.4 5α-reductase inhibitors significantly reduce the synthesis of prostate-specific antigen (PSA), a protein made by the epithelial cells of the prostate. We propose that the actual reduction in prostate tissue PSA concentration over time might result in the promotion of high-grade prostate cancer. Furthermore, we feel this needs serious attention by the medical community given the widespread use of these drugs to treat both benign prostatic hyperplasia (BPH) and male pattern baldness.5 Histologic prostate cancer is exceedingly common in the USA; autopsy data reveal that latent prostate cancer is present in 30% of men in their 30s, 50% of men in their 50 s and more …

α1-Adrenergic Blockers and Intraoperative Floppy-Iris Syndrome

JAMA Association Between Tamsulosin and Serious Ophthalmic Adverse Events in Older Men Following Cataract Surgery Chaim M. Bell, MD, PhD; Wendy V. Hatch, OD, MSc; Hadas D. Fischer, MD; Geta Cernat, MD, MSc; J. Michael Paterson, MSc; Andrea Gruneir, PhD; Sudeep S. Gill, MD, MSc; Susan E. Bronskill, PhD; Geoffrey M. Anderson, MD, PhD; Paula A. Rochon, MD, MPH Context: Both benign prostatic hyperplasia (BPH) and cataract formation are common in older men. The α-adrenergic receptor blocker tamsulosin is frequently prescribed to treat BPH, and research suggests this drug may increase the intraoperative difficulty of cataract surgery. No studies have documented whether use of tamsulosin or other α-blocker drug therapies affect the risk of serious postoperative adverse events. Objective: To assess the risk of adverse events following cataract surgery in older men prescribed tamsulosin or other α-blocking drugs used to treat BPH. Design, Setting, and Patients: Nested case-control analysis of a population-based retrospective cohort study using linked health care databases from Ontario, Canada. We included all men aged 66 years or older who had cataract surgery between 2002 and 2007 (N = 96 128). Main Outcome Measures: A composite of procedures signifying retinal detachment, lost lens or lens fragment, or endophthalmitis occurring within 14 days after cataract surgery. The risk of these adverse events was compared between men treated with tamsulosin or other α-blockers and men with no exposure to these medications in the year prior to cataract surgery. We separately examined the association of drug exposure that was either recent (within the 14 days before surgery) or previous (15-365 days before surgery). Results: Overall, 3550 patients (3.7%) in the cohort had recent exposure to tamsulosin and 7426 patients (7.7%) had recent exposure to other α-blockers. Two hundred eighty-four patients (0.3%) had an adverse event. We randomly matched 280 of the cases to 1102 controls according to their age, surgeon, and year of surgery. Adverse events were significantly more common among patients with recent tamsulosin exposure (7.5% vs 2.7%; adjusted odds ratio [OR], 2.33; 95% confidence interval [CI], 1.22-4.43) but were not associated with recent exposure to other α-blockers (7.5% vs 8.0%; adjusted OR, 0.91; 95% CI, 0.54-1.54) or to previous exposure to either tamsulosin (1.8% vs 1%; adjusted OR, 0.94; 95% CI, 0.27-3.34) or other α-blockers (2.9% vs 2.1%; adjusted OR, 1.08; 95% CI, 0.47-2.48). This corresponds to an estimated number needed to harm (NNH) of 255 (95% CI, 99-1666). Conclusions: Exposure to tamsulosin within 14 days of cataract surgery was significantly associated with serious postoperative ophthalmic adverse events. There were no significant associations with exposure to other α-blocker medications used to treat BPH. JAMA. 2009;301(19):1991-1996..

Association Between Tamsulosin and Serious Ophthalmic Adverse Events in Older Men Following Cataract Surgery

Both benign prostatic hyperplasia (BPH) and cataract formation are common in older men. The alpha-adrenergic receptor blocker tamsulosin is frequently prescribed to treat BPH, and research suggests this drug may increase the intraoperative difficulty of cataract surgery. No studies have documented whether use of tamsulosin or other alpha-blocker drug therapies affect the risk of serious postoperative adverse events. To assess the risk of adverse events following cataract surgery in older men prescribed tamsulosin or other alpha-blocking drugs used to treat BPH. Nested case-control analysis of a population-based retrospective cohort study using linked health care databases from Ontario, Canada. We included all men aged 66 years or older who had cataract surgery between 2002 and 2007 (N = 96 128). A composite of procedures signifying retinal detachment, lost lens or lens fragment, or endophthalmitis occurring within 14 days after cataract surgery. The risk of these adverse events was compared between men treated with tamsulosin or other alpha-blockers and men with no exposure to these medications in the year prior to cataract surgery. We separately examined the association of drug exposure that was either recent (within the 14 days before surgery) or previous (15-365 days before surgery). Overall, 3550 patients (3.7%) in the cohort had recent exposure to tamsulosin and 7426 patients (7.7%) had recent exposure to other alpha-blockers. Two hundred eighty-four patients (0.3%) had an adverse event. We randomly matched 280 of the cases to 1102 controls according to their age, surgeon, and year of surgery. Adverse events were significantly more common among patients with recent tamsulosin exposure (7.5% vs 2.7%; adjusted odds ratio [OR], 2.33; 95% confidence interval [CI], 1.22-4.43) but were not associated with recent exposure to other alpha-blockers (7.5% vs 8.0%; adjusted OR, 0.91; 95% CI, 0.54-1.54) or to previous exposure to either tamsulosin (< or = 1.8% vs 1%; adjusted OR, 0.94; 95% CI, 0.27-3.34) or other alpha-blockers (2.9% vs 2.1%; adjusted OR, 1.08; 95% CI, 0.47-2.48). This corresponds to an estimated number needed to harm (NNH) of 255 (95% CI, 99-1666). Exposure to tamsulosin within 14 days of cataract surgery was significantly associated with serious postoperative ophthalmic adverse events. There were no significant associations with exposure to other alpha-blocker medications used to treat BPH.

Tissue and serum levels of principal androgens in benign prostatic hyperplasia and prostate cancer

Androgens are considered to play a substantial role in pathogenesis of both benign prostatic hyperplasia (BPH) and prostate cancer. The importance of determination of androgen levels in tissue and serum for cancer progression and prognosis has been poorly understood. The aim of study was to find out hormonal differences in both diseases, their correlations between intraprostatic and serum levels and predictotory value of their investigation. Testosterone, dihydrotestosterone, androstenedione and also epitestosterone were determined in prostate tissue from 57 patients who underwent transvesical prostatectomy for BPH and 121 patients after radical prostatectomy for prostate cancer. In 75 subjects with cancer and 51 with BPH the serum samples were analyzed for testosterone, dihydrotestosterone and SHBG. Significantly higher intraprostatic androgen concentrations, i.e. 8.85 ± 6.77 versus 6.44 ± 6.43 pmol/g, p < 0.01 for dihydrotestosterone, and 4.61 ± 7.02 versus 3.44 ± 4.53 pmol/g, p < 0.05 for testosterone, respectively, were found in patients with prostate cancer than in BPH. Higher levels in cancer tissue were found also for epitestosterone. However, no differences were found in serum levels. Highly significant correlations occurred between all pairs of intraprostatic androgens and also epitestosterone as well as between serum testosterone and dihydrotestosterone ( p < 0.001) in both BPH and cancer groups. Correlation was not found between corresponding tissue and serum testosterone and dihydrotestosterone, either in benign or cancer samples. The results point to importance of intraprostatic hormone levels for evaluation of androgen status of patients, contrasting to a low value of serum hormone measurement.

Androgen Regulation of JM-27 is Associated With the Diseased Prostate

Despite intense research efforts, the etiology of prostatic hyperplasia associated with both benign prostatic hyperplasia (BPH) and prostate cancer remains poorly understood. Our previous studies using array technology identified JM-27 as a transcript that is dramatically up-regulated in the prostates of patients with symptomatic BPH and in normal, adjacent prostatic regions of patients with prostate cancer. In the present study, using an extended sample set, we show a correlation between the messenger RNA and protein expression of JM-27. To investigate the possible functions of this gene, its expression in the rat prostate was examined by immunoblot analysis using a polyclonal antibody specific to human JM-27. This antibody reacts with 2 rat polypeptides of 17 kd and 27 kd in size. Whereas the 27-kd form of the JM-27 protein found in human prostate is selectively expressed in the dorsolateral lobes of the rat prostate, the 17-kd form is expressed only in the ventral lobe. Expression of both forms of this protein appears to be androgen-regulated. There is a time-dependent decrease in expression of the protein products in the ventral and dorsolateral lobes of the rat prostate after castration. Administration of exogenous testosterone in castrated animals maintains protein expression in both lobes. Androgens are believed to play a central role in prostate growth and development, and therefore, it is tempting to speculate that JM-27, an androgen-regulated gene, may be involved in prostatic growth regulation. Further studies are underway to evaluate such a function for JM-27 in prostatic diseases.

CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro

The direct relationship between the aging process and the incidence and prevalence of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) implies that certain risk factors associated with the development of both diseases increase with the aging process. In particular, both diseases share an overly proliferative phenotype, suggesting that mechanisms that normally act to suppress cellular proliferation are disrupted or rendered dysfunctional as a consequence of the aging process. We propose that one such mechanism involves changes in the prostate microenvironment, which 'evolves' during the aging process and disrupts paracrine interactions between epithelial and associated stromal fibroblasts. We show that stromal fibroblasts isolated from the prostates of men 63-81 years of age at the time of surgery express and secrete higher levels of the CXCL12 chemokine compared with those isolated from younger men, and stimulate CXCR4-mediated signaling pathways that induce cellular proliferation. These studies represent an important first step towards a mechanistic elucidation of the role of aging in the etiology of benign and malignant prostatic diseases.