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Islami F.,Mount Sinai School of Medicine | Islami F.,Surveillance and Health Services Research | Islami F.,Tehran University of Medical Sciences | Moreira D.M.,Arthur Smith Institute for Urology | And 3 more authors.
European Urology | Year: 2014

Context An association between tobacco smoking and prostate cancer (PCa) incidence and mortality was suggested in an earlier meta-analysis of 24 prospective studies in which dose-response associations and risks per unit of tobacco use were not examined.Objective We investigated the association between several measures of tobacco use and PCa mortality (primary outcome) and incidence (secondary outcome) including dose-response association. Evidence acquisition Relevant articles from prospective studies were identified by searching the PubMed and Web of Science databases (through January 21, 2014) and reference lists of relevant articles. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects methods. We also calculated population attributable risk (PAR) for smoking and PCa mortality. Evidence synthesis We included 51 articles in this meta-analysis (11 823 PCa deaths, 50 349 incident cases, and 4 082 606 cohort participants). Current cigarette smoking was associated with an increased risk of PCa death (RR: 1.24; 95% CI, 1.18-1.31), with little evidence for heterogeneity and publication bias. The number of cigarettes smoked per day had a dose-response association with PCa mortality (p = 0.02; RR for 20 cigarettes per day: 1.20). The PAR for cigarette smoking and PCa deaths in the United States and Europe were 6.7% and 9.5%, respectively, corresponding to >10 000 deaths/year in these two regions. Current cigarette smoking was inversely associated with incident PCa (RR: 0.90; 95% CI, 0.85-0.96), with high heterogeneity in the results. However, in studies completed in 1995 or earlier (considered as completed before the prostate-specific antigen screening era), ever smoking showed a positive association with incident PCa (RR: 1.06; 95% CI, 1.00-1.12) with little heterogeneity.Conclusions Combined evidence from observational studies shows a modest but statistically significant association between cigarette smoking and fatal PCa. Smoking appears to be a modifiable risk factor for PCa death.Patient summary Smoking increases the chance of prostate cancer death. Not smoking prevents this harm and many other tobacco-related diseases. © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved. Source

Muller R.L.,Duke University | Muller R.L.,Veterans Affairs Medical Center | Gerber L.,Duke University | Gerber L.,Veterans Affairs Medical Center | And 5 more authors.
European Urology | Year: 2012

Background: Findings of studies on the association between androgens and prostate cancer (PCa) are mixed. Androgens may affect prostate-specific antigen (PSA) levels, thereby influencing biopsy recommendations. Also, androgens may stimulate prostate growth at very low levels with no additional effects at higher levels (saturation model). Objective: To test whether androgens were associated with PCa risk in the placebo arm of a prospective study in which biopsies were performed regardless of PSA level. Design, setting, and participants: Of 8122 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, 4073 men (50.1%) received placebo. Key entry criteria were PSA 2.5-10 ng/ml and one prior negative biopsy. Intervention: Per-protocol biopsies at 2 and 4 yr; for-cause biopsies at physician discretion. Outcome measurements and statistical analysis: Multivariable logistic regression was used to test the association between baseline log-transformed testosterone and dihydrotestosterone (DHT) levels and the risk of detecting either PCa or low-grade PCa (Gleason score <6) compared with high-grade PCa (Gleason score >7). In secondary analysis, we stratified the analysis by low baseline androgen levels (testosterone <10 nmol/l; DHT <0.76 nmol/l) compared with normal baseline androgen levels. Results and limitations: Of 4073 men, 3255 (79.9%) had at least one biopsy after randomization and were analyzed. Androgen levels tested continuously or by quintiles were generally unrelated to PCa detection or grade. PCa detection was similar among men with low compared with normal baseline testosterone levels (25.5% and 25.1%; p = 0.831). In secondary analysis, higher testosterone levels at baseline were associated with higher PCa detection (odds ratio: 1.23; 95% confidence interval, 1.06-1.43; p = 0.006) only if men had low baseline testosterone (<10 nmol/l). For men with normal baseline testosterone (≥10 nmol/l), higher testosterone levels at baseline were unrelated to PCa risk (p = 0.33). No association was found for DHT and PCa (all p > 0.85). Conclusions: Baseline serum testosterone and DHT levels were unrelated to PCa detection or grade. Our findings of the lowest testosterone levels being associated with the lowest PCa risk with no further changes with higher testosterone support a saturation model but must be confirmed in future studies using an a priori defined hypothesis. ClinicalTrials.gov identifier: NCT00056407. © 2012 European Association of Urology. Source

Muller R.L.,Duke University | Muller R.L.,Veterans Affairs Medical Center | Gerber L.,Duke University | Gerber L.,Veterans Affairs Medical Center | And 7 more authors.
European Urology | Year: 2013

Background: Although obesity has been associated with larger prostate volumes (PV), few studies have actually investigated whether obesity enhances PV growth, especially among men using 5α-reductase inhibitors. Objective: To examine whether obesity is associated with enhanced PV growth measured by serial transrectal ultrasound (TRUS) measurements. Design, setting, and participants: We conducted a secondary analysis of the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, which was originally aimed at cancer risk reduction among high-risk men with a single negative prestudy biopsy. Intervention: Per-protocol randomization to placebo or dutasteride and mandatory TRUS-guided biopsies at 2 yr and 4 yr. Outcome measurements and statistical analysis: Percentage change in PV at 2 yr and 4 yr from baseline. We tested its association with baseline body mass index (BMI) groups of <25, 25-29.9, and ≥30 kg/m2 using multivariable linear regression. Secondarily, we tested whether BMI was associated with the likelihood of having no PV reduction among men randomized to dutasteride using multivariable logistic regression. Results and limitations: Of 8122 participants, we analyzed 71.8% and 54.5% with complete 2-yr and 4-yr PV data, respectively. In multivariable analysis, men on placebo with BMI ≥30 versus <25 kg/m2 had enhanced PV growth from baseline (at 2 yr: 17.0% vs 10.7%, p < 0.001; at 4 yr: 29.4% vs 20.1%; p = 0.001). Men on dutasteride with BMI ≥30 versus <25 kg/m2 had attenuated PV reduction from baseline (at 2 yr: -14.3% vs -18.5%; p = 0.002; at 4 yr: -13.2% vs -19.3%; p = 0.001) and higher likelihood of having no PV reduction (at 2 yr: odds ratio [OR]: 1.44; 95% confidence interval [CI], 1.08-1.93; p = 0.014; at 4 yr: OR: 1.62; 95% CI, 1.18-2.22; p = 0.003). We found no significant interactions between BMI and dutasteride on PV change at 2 yr and 4 yr (p interaction ≥0.36). No clinical outcomes or effects of weight change were assessed. Conclusions: Obesity enhanced PV growth and attenuated PV reduction by dutasteride. The null interaction between obesity and dutasteride for PV change implies that the effect of obesity on dutasteride-treated men is likely a combination of dutasteride-driven PV reduction with obesity-driven PV growth rather than decreased dutasteride efficacy. ClinicalTrials.gov identifier: NCT00056407. © 2013 European Association of Urology. Source

Levey H.R.,Arthur Smith Institute for Urology | Kutlu O.,Johns Hopkins Hospital | Bivalacqua T.J.,Johns Hopkins Hospital
Asian Journal of Andrology | Year: 2012

Priapism is defined as a prolonged and persistent erection of the penis without sexual stimulation. This is a poorly understood disease process with little information on the pathophysiology of this erectile disorder. Complications from this disorder are devastating due to the irreversible erectile damage and resultant erectile dysfunction (ED). Stuttering priapism, though relatively rare, affects a high prevalence of men with sickle-cell disease (SCD) and presents a challenging problem with guidelines for treatment lacking or resulting in permanent ED. The mechanisms involved in the development of priapism in this cohort are poorly characterized; therefore, medical management of priapism represents a therapeutic challenge to urologists. Additional research is warranted, so we can effectively target treatments for these patients with prevention as the goal. This review gives an introduction to stuttering priapism and its clinical significance, specifically with regards to the patient with SCD. Additionally, the proposed mechanisms behind its pathophysiology and a summary of the current and future targets for medical management are discussed. © 2012 AJA, SIMM &SJTU. All rights reserved. Source

Baxter C.,Arthur Smith Institute for Urology | Kim J.-H.,University of California at Los Angeles
Current Urology Reports | Year: 2010

Sacral neuromodulation is increasingly used for the treatment of voiding dysfunction, pelvic pain syndromes, and gastrointestinal disorders. While increased use of this technology has led to a greater understanding of its potential as well as its limitations, difficulty persists in identifying the patients that will benefit most. Either of two trial stimulation techniques is performed before placement of a permanent neuromodulator: the monopolar percutaneous nerve evaluation and the tined quadripolar staged trial. The preponderance of recent literature asserts the superior sensitivity of the staged trial over percutaneous nerve evaluation. However, the techniques offer disparate advantages, and other issues, such as cost-effectiveness, remain largely unexplored. The role of sacral neuromodulation will continue to expand as physicians and patients become increasingly aware of its therapeutic potential. Widespread adoption of this clinically superior technique will most rapidly help the greatest number of patients. © 2010 The Author(s). Source

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