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Introduction: We sought to determine if outcomes of Bacillus Calmette-Guerin (BCG) therapy in patients with non-muscle-invasive bladder cancer (NMIBC) vary by race., Methods: A retrospective chart review was conducted on 149 patients treated with BCG for intermediate- and high-risk NMIBC between 2001 and 2018, and who were followed up for cancer recurrence through March 2019.The primary outcomes were disease-free survival (DFS), low-grade disease-free survival (LGDFS), high-grade disease-free survival (HGDFS), and progression-free survival (PFS) at five years. Kaplan-Meier survival curves stratified by race (African American vs non-African American) were analyzed for all the above outcomes and multivariate Cox regression analyses were also performed to compare recurrence differences by race, after adjusting for age, sex, initial stage and grade., Results: Of the 149 patients, 37.6% were Caucasian, 24.8% were African American, 26.8% were Hispanic, and 10.7% were of other/unknown race. Disease stage at initial presentation was 65.1% Ta, 34.9% T1, and 18.1% CIS. African American patients (N=37) did not have evidence for worse outcomes compared to non-African American patients when considering DFS (54.1% vs. 65.7%, p = 0.202), HGDFS (58.8% vs. 71.7%, p = 0.158), and PFS (83.8% vs. 92.6%, p = 0.117) at five years. Multivariate analysis did not reveal statistically significant racial differences in recurrence or progression., Conclusions: African Americans with NMIBC did not have worse disease recurrence and progression after receiving intravesical BCG treatment. Although there did appear to be a trend towards worse oncologic outcomes in African Americans, larger studies are needed to validate this finding.

Background Severe coronavirus disease 2019 (COVID-19) is characterized by a proinflammatory state with high mortality. Statins have anti-inflammatory effects and may attenuate the severity of COVID-19. Methods and Results An observational study of all consecutive adult patients with COVID-19 admitted to a single center located in Bronx, New York, was conducted from March 1, 2020, to May 2, 2020. Patients were grouped as those who did and those who did not receive a statin, and in-hospital mortality was compared by competing events regression. In addition, propensity score matching and inverse probability treatment weighting were used in survival models to examine the association between statin use and death during hospitalization. A total of 4252 patients were admitted with COVID-19. Diabetes mellitus modified the association between statin use and in-hospital mortality. Patients with diabetes mellitus on a statin (n=983) were older (69±11 versus 67±14 years; P <0.01), had lower inflammatory markers (C-reactive protein, 10.2; interquartile range, 4.5-18.4 versus 12.9; interquartile range, 5.9-21.4 mg/dL; P <0.01) and reduced cumulative in-hospital mortality (24% versus 39%; P <0.01) than those not on a statin (n=1283). No difference in hospital mortality was noted in patients without diabetes mellitus on or off statin (20% versus 21%; P =0.82). Propensity score matching (hazard ratio, 0.88; 95% CI, 0.83-0.94; P <0.01) and inverse probability treatment weighting (HR, 0.88; 95% CI, 0.84-0.92; P <0.01) showed a 12% lower risk of death during hospitalization for statin users than for nonusers. Conclusions Statin use was associated with reduced in-hospital mortality from COVID-19 in patients with diabetes mellitus. These findings, if validated, may further reemphasize administration of statins to patients with diabetes mellitus during the COVID-19 era.

Background: The opioid epidemic has been influenced in part by physician overprescribing. Several studies have evaluated opioid use after urogynecologic surgery, with limited data on postoperative guidelines. The objective of this study was to investigate the effect of implementing a multimodal, opioid-sparing analgesia regimen on opioid use, patient satisfaction, and refill rates., Materials and Methods: This was a retrospective observational study of female patients undergoing urogynecologic surgery at an academic center from 2017 to 2019, before and after introduction of an opioid-sparing multimodal regimen protocol advocating for standing ibuprofen and acetaminophen. Demographic information, opioid prescription details (oral morphine equivalent [OME]), and refill rate data were collected from the chart. Postoperative opioid use and satisfaction score (for the after group using Likert scale) was obtained by telephone survey. t Test was used to compare continuous variables, and χ2/Fischer exact test was used to compare categorical variables., Results: Two hundred ninety-two patients were eligible and contacted. One hundred one patients responded before protocol implementation and 102 responded after protocol implementation. The median number of tablets prescribed was 14.5 (108.5 OME; IQR, 10) and 10 (75 OME; IQR, 5; P < 0.01) preprotocol and postprotocol, whereas the mean number of tablets used was 10 (75 OME; IQR, 13) and 3 (22.5 OME; IQR, 10; P = 0.0009) preprotocol and postprotocol, respectively. Refill rate did not differ significantly (11% preprotocol vs 7% postprotocol P = 0.32) Mean satisfaction score was 4.3 (SD, 0.9)., Conclusions: A multimodal analgesia regimen limiting postoperative opioids decreased postoperative opioid prescribing and consumption while maintaining similar patient satisfaction and refill rates., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2020 American Urogynecologic Society. All rights reserved.)

Purpose: Increased adrenergic innervation is observed in prostate cancer (CaP) and is associated with aggressive disease. Emerging evidence suggests that beta-adrenergic blockade inhibits CaP progression. However, the association between type of beta-blocker use and risk of incident CaP on initial prostate biopsy has not been investigated in multiethnic populations., Materials and Methods: A retrospective study of racially/ethnically diverse men (64% African-American and Hispanic), who underwent initial prostate biopsy between 2006 and 2016 in a large healthcare system was performed. Oral use of beta-blocker type was assessed by reviewing active prescriptions within the 5-year period preceding initial biopsy. Patient demographics and clinical factors were collected., Results: Of 4,607 men who underwent initial prostate biopsy, 4,516 met criteria and 2,128 had a biopsy positive for CaP; 20% high-risk, 41% intermediate-risk, and 39% low or very-low risk (National Comprehensive Cancer Network classification). Overall, 15% of patients were taking a beta-blocker prior to initial biopsy, with Metoprolol, Atenolol, and Carvedilol accounting for the majority. Of beta-blocker types, Atenolol alone was associated with a 38% reduction in odds of incident CaP (P= 0.01), with a 40% and 54% reduction in risks of National Comprehensive Cancer Network intermediate and high-risk CaP (P = 0.03 and P = 0.03, respectively) compared to men not taking a beta-blocker. Furthermore, longer duration of Atenolol use (3-5 years) was associated with a 54% and 72% reduction in intermediate and high-risk disease, (P = 0.03 and P = 0.03, respectively)., Conclusions: Among beta blocker types, long-term Atenolol use is associated with a significant reduction in incident CaP risk on initial prostate biopsy for clinically-significant intermediate and high-risk disease compared to men not taking a beta-blocker., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array. SIGNIFICANCE: This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers., (©2020 American Association for Cancer Research.)

To determine whether patients with ureteral stones received different standard of care in the emergency department (ED) according to various sociodemographic factors. We conducted a retrospective study of patients presenting to EDs in a large tertiary-care hospital in the Bronx, New York with a diagnosis of ureteral stones. Electronic chart review was used to assess each patient's ED course and to gather socio-demographic information. The primary outcomes of interest were administration of pain medication, prescription of alpha-1 antagonists to facilitate stone passage, and whether or not patients received CT scan or ultrasound. Associations of these outcomes with age categories, sex, race/ethnicity, BMI category, socioeconomic status and insurance status were examined using multivariate logistic regression models. 1200 patients were included in this analysis of which 616 (51%) were women. A large proportion of patients were minorities: 40% Hispanic, 15% non-Hispanic Black, and 20% other/multiracial. Patients aged 55-64 years and those 65 or older were less likely to receive pain medication compared to patients < 35 years (OR = 0.48, 95% CI 0.27-0.86, p = 0.01 and OR = 0.46, 95% CI 0.21-1.00, p = 0.05, respectively). Women were less likely than men to undergo any form of diagnostic imaging (OR = 0.52, 95% CI 0.35-0.76, p = 0.001). Similarly, patients in the lowest quintile of SES received less imaging than patients in the highest SES group (OR = 0.50, 95% CI 0.27-0.90, p = 0.02). Finally, women were less likely to receive alpha blockade compared to men (OR = 0.68, 95% CI 0.49-0.92, p = 0.014). Multiple disparities exist among patients presenting to the emergency department for ureteral stones.

Objectives: This study aimed to identify differences in severity of overactive bladder (OAB) symptoms in women of different races and ethnicities using urodynamic study (UDS) parameters., Methods: We performed a 5-year retrospective chart review from January 2014 to January 2019 of women 18 years and older who endorsed OAB symptoms and underwent UDS at a racially and ethnically diverse academic urban medical center. Logistic and linear regressions were used to examine the associations of various UDS parameters between racial/ethnic groups, after adjusting for age, diabetes, and parity., Results: A total of 161 women with an average age of 59 years were included in the study. The racial/ethnic composition of the group was Hispanic (62%), black (24%), and white (11%). Symptoms on presentation included urgency and/or frequency (11.8%), urge incontinence (23.0%), or mixed urinary symptoms (65.2%). Black and Hispanic women presented with differing symptoms (urgency/frequency vs mixed urinary symptoms). Half of the patients (n = 82) had detrusor overactivity. Compared with whites, blacks were 3.4-fold more likely to have detrusor overactivity (95% confidence interval, 0.99-11.40) and had lower volumes at time of "strong desire" (-102.6 mL, P = 0.003). Hispanics had on average 75.88 mL less volume at sensation of "strong desire" (P = 0.016) than did whites., Conclusions: Our study suggests that minority race and ethnicity may be associated with worse performance on certain UDS parameters. Future studies should aim to understand if these differences are due to genetic, disease-related, behavioral, and/or socioeconomic factors and whether these differences are associated with worse subjective OAB.

Background: Increased cancer risk has been reported in Parkinson's disease (PD) patients carrying the leucine rich repeat kinase 2 (LRRK2) G2019S mutation (LRRK2-PD) in comparison with idiopathic PD (IPD). It is unclear whether the elevated risk would be maintained when compared with unaffected controls., Methods: Cancer outcomes were compared among 257 LRRK2-PD patients, 712 IPD patients, and 218 controls recruited from 7 LRRK2 consortium centers using mixed-effects logistic regression. Data were then pooled with a previous study to examine cancer risk between 401 LRRK2-PD and 1946 IPD patients., Results: Although cancer prevalence was similar among LRRK2-PD patients (32.3%), IPD patients (27.5%), and controls (27.5%; P = 0.33), LRRK2-PD had increased risks of leukemia (odds ratio [OR] = 4.55; 95% confidence interval [CI], 1.46-10.61) and skin cancer (OR = 1.61; 95% CI, 1.09-2.37). In the pooled analysis, LRRK2-PD patients had also elevated risks of leukemia (OR = 9.84; 95% CI, 2.15-44.94) and colon cancer (OR = 2.34; 95% CI, 1.15-4.74) when compared with IPD patients., Conclusions: The increased risks of leukemia as well as skin and colon cancers among LRRK2-PD patients suggest that LRRK2 mutations heighten risks of certain cancers. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

Purpose: Based on prior reports demonstrating that neutral endopeptidase (NEP) inhibitors increase sperm motility, the goal of our studies was to identify endogenous seminal peptides that inhibit NEP and investigate their potential effect on sperm motility., Methods: Peptidomic analysis was performed on human seminal fluid, identifying 22 novel peptides. One peptide, named RSIY-11, derived from semenogelin-1, was predicted through sequence analysis to be a substrate and/or potential inhibitor of NEP. Enzymatic analysis was conducted to determine the inhibitory constant (Ki) of RSIY-11 as an inhibitor of NEP. Total and progressive sperm motility was determined at baseline and 30 and 60 min following addition of RSIY-11 to seminal fluid in 59 patients undergoing an infertility workup at an urban medical center. Additionally, the effects of RSIY-11 on sperm motility were evaluated in 15 of the 59 patients that met criteria for asthenospermia., Results: RSIY-11 was shown to act as a competitive inhibitor of NEP with a Ki of 18.4 ± 1.6 μM. Addition of RSIY-11 at concentrations of 0.75 μM, 7.5 μM, and 75 μM significantly increased sperm motility at all time points investigated, with increases of 6.1%, 6.9%, and 9.2% at 60 min, respectively. Additionally, within the subgroup of patients with asthenospermia, RSIY-11 at concentrations of 0.75 μM, 7.5 μM, and 75 μM significantly increased sperm motility at all time points investigated, with increases of 7.6%, 8.8%, and 10.6% at 60 min, respectively., Conclusions: RSIY-11 is a newly identified semenogelin-1-derived peptide present in seminal fluid. RSIY-11 acts as a potent competitive inhibitor of NEP, which when added to seminal fluid significantly increases sperm motility. RSIY-11 could play a potential role in the treatment for male factor infertility related to asthenospermia and improve intrauterine insemination outcomes.

Urinary stone disease (USD) is a major health concern. There is a need for new treatment modalities. Recently, our group provided evidence for an association between the GMB composition and USD. The accessibility of the Gut Microbiome (GMB) makes it an attractive target for investigation and therefore, in these studies we have evaluated the extent to which the whole gut microbial community in fecal transplants can affect urinary stone risk parameters in an animal model. Fresh fecal pellets were collected from Zucker lean rats, homogenized in PBS (100 mg/mL), filtered through a 70 μm strainer and then orally gavaged into C57BL/6NTac germ-free mice. Twenty-four hours urine collections and GMB analysis were performed over time for 1 month. Kidney and gut tissue were harvested from transplanted mice for western blot analysis of expression levels of the Slc26a6 transporter involved in oxalate balance. Urinary calcium decreased after fecal transplant by 55% (P < 0.001). Urinary oxalate levels were on average 24% lower than baseline levels (P < 0.001). Clostridiaceae family was negatively correlated with urinary oxalate at 4 weeks after transplant (r = -0.83, P < 0.01). There was a 0.6 unit average increase in urinary pH from a baseline of 5.85 (SE ± 0.028) to 6.49 (SE ± 0.04) (P < 0.001) after transplant. There was a concomitant 29% increase in gastrointestinal alkali absorption (P < 0.001) 4-weeks after fecal transplant. Slc26a6 expression increased by 90% in the cecum after transplant. Our results suggest that the gut microbiome may impact metabolism, alters urinary chemistry, and thereby may influence USD; the accessibility of the GMB can potentially be leveraged for therapeutic interventions., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Opioid abuse is a growing epidemic in the United States, with opioid overdose becoming a leading cause of death. There is wide variation in prescription practices for post-operative opioids due to absence of guidelines. The purpose of this study is to examine postoperative opioid prescribing patterns after urogynecologic surgery and determine usage and management of opioid pills by patients., Materials and Methods: This is an observational, prospective study of female patients (N = 143) who underwent urogynecologic (prolapse or incontinence) surgery from June to December 2017 at a single academic center. Patients were surveyed regarding their pain medication use 30 days postoperatively. Survey questions included preoperative pain medication use, quantity of opioid pills consumed, need for additional opioid prescription, and management of remaining pills. T-test and one-way Anova were used for comparison of continuous variables and chi-squared test used for comparison of categorical variables., Results: Of 143 eligible patients, 99 (69%) responded; 62% of respondent patients underwent vaginal surgery, 22% abdominal surgery with or without vaginal surgery, and 15% underwent other procedures. Postoperatively, 81.8% of patients were prescribed opioids. The average number of tablets prescribed ranged from 12.4 to 17.4 depending on the procedure. 54.3% of patients reported using less than half of their prescribed opioid prescription. Of the patients who had excess opioid tablets, only 8.6% reported discarding their opioids., Conclusion: To date, no guidelines exist on prescribing opioids postoperatively. Opioids are overprescribed post-operatively with over half of patients using less than half of the opioids prescribed to them., (© 2018 Wiley Periodicals, Inc.)

Background: Several studies have examined association between human papillomaviruses (HPV) and esophageal cancer, but results have been inconsistent. This is the first prospective study to investigate associations between α, β and γ HPV detection in the oral cavity and risk of esophageal cancer. Methods: We conducted a nested case-control study among 96,650 cancer-free participants in the American Cancer Society Cancer Prevention Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Incident esophageal cancer cases ( n = 125) were identified during an average 3.9 years of follow-up. Three controls per case ( n = 372) were selected and matched on age, sex, race/ethnicity, and time since mouthwash collection. α, β, and γ HPV DNA in oral samples were detected using a next-generation sequencing assay. Conditional logistic regression models were used to estimate OR and 95% confidence intervals (CIs), adjusting for smoking and alcohol consumption. Statistical significance was evaluated using permutation test. Results: Prevalence of oral α, β, and γ HPV was 18.4%, 64.8%, and 42.4% in cases and 14.3%, 55.1%, and 33.6% in controls, respectively. Oral HPV16 detection was not associated with esophageal cancer (OR = 0.54, 95% CI, 0.1-4.84) and none of the esophageal squamous cell carcinoma cases ( n = 28) were HPV16 positive. Some oral HPV types were more common in cases than controls; however, none of the associations were statistically significant. Conclusions: Although HPVs in the oral cavity are very common, this study showed no evidence of association between oral HPVs and esophageal cancer. Impact: Oral HPVs may not contribute to risk of esophageal cancer. Cancer Epidemiol Biomarkers Prev; 27(10); 1168-75. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Purpose: Health research in low- and middle-income countries can generate novel scientific knowledge and improve clinical care, fostering population health improvements to prevent premature death. Project management is a critical part of the success of this research, applying knowledge, skills, tools, and techniques to accomplish required goals. Here, we describe the development and implementation of tools to support a multifaceted study of prostate cancer in Africa, focusing on building strategic and operational capacity., Methods: Applying a learning organizational framework, we developed and implemented a project management toolkit (PMT) that includes a management process flowchart, a cyclical center-specific schedule of activities, periodic reporting and communication, and center-specific monitoring and evaluation metrics., Results: The PMT was successfully deployed during year one of the project with effective component implementation occurring through periodic cycles of dissemination and feedback to local center project managers. A specific evaluation was conducted 1 year after study initiation to obtain enrollment data, evaluate individual quality control management plans, and undertake risk log assessments and follow-up. Pilot data obtained identified areas in which centers required mentoring, strengthening, and capacity development. Strategies were implemented to improve project goals and operational capacity through local problem solving, conducting quality control checks and following compliancy with study aims. Moving forward, centers will perform quarterly evaluations and initiate strengthening measures as required., Conclusion: The PMT has fostered the development of both strategic and operational capacity across project centers. Investment in project management resources is essential to ensuring high-quality, impactful health research in low- and middle-income countries.

Purpose: Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA., Methods: We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array., Results: We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories., Conclusion: We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.

Importance: Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC., Objective: To prospectively examine associations between the oral microbiome and incident HNSCC., Design, Setting, and Participants: This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline., Exposures: Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant., Main Outcomes and Measures: Incident HNSCC., Results: The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco smokers, tended to have greater alcohol consumption (among drinkers), and to be positive for oral carriage of papillomavirus-16. Overall microbiome composition was not associated with risk of HNSCC. Greater abundance of genera Corynebacterium (fold change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80; q = .06) and Kingella (FC, 0.63; 95% CI, 0.46-0.86; q = .08) were associated with decreased risk of HNSCC, potentially owing to carcinogen metabolism capacity. These findings were consistent for both cohorts and by cohort follow-up time. The observed relationships tended to be stronger for larynx cancer and for individuals with a history of tobacco use., Conclusions and Relevance: This study demonstrates that greater oral abundance of commensal Corynebacterium and Kingella is associated with decreased risk of HNSCC, with potential implications for cancer prevention.

Background: The follow-up rate, a standard index of the completeness of follow-up, is important for assessing the validity of a cohort study. A common method for estimating the follow-up rate, the "Percentage Method", defined as the fraction of all enrollees who developed the event of interest or had complete follow-up, can severely underestimate the degree of follow-up. Alternatively, the median follow-up time does not indicate the completeness of follow-up, and the reverse Kaplan-Meier based method and Clark's Completeness Index (CCI) also have limitations., Methods: We propose a new definition for the follow-up rate, the Person-Time Follow-up Rate (PTFR), which is the observed person-time divided by total person-time assuming no dropouts. The PTFR cannot be calculated directly since the event times for dropouts are not observed. Therefore, two estimation methods are proposed: a formal person-time method (FPT) in which the expected total follow-up time is calculated using the event rate estimated from the observed data, and a simplified person-time method (SPT) that avoids estimation of the event rate by assigning full follow-up time to all events. Simulations were conducted to measure the accuracy of each method, and each method was applied to a prostate cancer recurrence study dataset., Results: Simulation results showed that the FPT has the highest accuracy overall. In most situations, the computationally simpler SPT and CCI methods are only slightly biased. When applied to a retrospective cohort study of cancer recurrence, the FPT, CCI and SPT showed substantially greater 5-year follow-up than the Percentage Method (92%, 92% and 93% vs 68%)., Conclusions: The Person-time methods correct a systematic error in the standard Percentage Method for calculating follow-up rates. The easy to use SPT and CCI methods can be used in tandem to obtain an accurate and tight interval for PTFR. However, the FPT is recommended when event rates and dropout rates are high.

Background: Cancers constitute a significant public health problem in Nigeria. Breast, cervix and prostate cancers are leading causes of cancer-related deaths. Changing diets, lifestyles, HIV/AIDS and macro-structural factors contribute to cancer morbidity and mortality. Poor health information linking cancer risk to individual behaviors, environmental pollutants and structural barriers undermine prevention/control efforts. Studies suggest increasing health literacy and empowering individuals to take preventive action will improve outcomes and mitigate impact on a weak health system., Methods: We obtained qualitative data from 80 men, women, and young adults in 11 focus groups to assess beliefs, risk-perceptions, preventive behaviors and perceptions of barriers and facilitators to cancer control in Ibadan, Nigeria and conducted thematic analysis., Results: Participants demonstrated awareness of cancers and mentioned several risk factors related to individual behaviors and the environment. Nonetheless, myths and misconceptions as well as micro, meso and macro level barriers impede prevention and control efforts., Conclusion: Developing and implementing comprehensive context-relevant health literacy interventions in community settings are urgently needed.Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Serum testosterone deficiency increases with aging. Age is also a major risk factor for prostate cancer (PrCa) and PCa tumors are more frequently diagnosed among men >65 years old. We evaluated the relationship between preoperative serum testosterone and clinical/ pathological features of PrCa in middle-aged and elderly patients., Methods: A total of 605 PrCa patients who underwent robotic-assisted radical prostatectomy between September 2010 and January 2013 at the University of Pennsylvania, and who had serum testosterone levels measured using Elecsys Testosterone II Immunoassay were included in this IRB-approved protocol. Androgen deficiency was determined as serum free testosterone (FT) <47 pg/ml and total testosterone (TT) <193 ng/dl. Demographic, clinical and tumor characteristics of men with low vs. normal TT or FT were compared using t-test or chi-square tests. Logistic regression was used to determine associations of clinical and pathological variables with FT or TT levels., Results: Among middle-aged men (45-64 years; n = 367), those with low FT and low TT had, on average, a higher BMI (29.7 vs. 27.4, P < 0.01; and 32.2 vs. 27.6; P < 0.01, respectively) and higher proportion of Gleason 8-10 PrCa (13.3% vs. 4.8%, P = 0.011; and 19.2% vs. 5.1%, P = 0.012) compared to men with normal FT and normal TT values. Patients with low FT had also higher number of positive cores on biopsy (3.9 vs. 3.1 P = 0.019) and greater tumor volume (7.9 ml vs. 6.1 ml, P = 0.045) compared to those with normal FT. Among men ≥65 years ( n = 135) there was no difference in prostatectomy specimens of PrCa between patients with low or normal FT or TT., Conclusion: Among men aged 45-64 years low serum pretreatment FT and TT predicted more aggressive features of PrCa in prostatectomy specimens. In middle-aged patients low testosterone levels measured pre-operatively may indicate more aggressive disease parameters.

Disruption of the blood-brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis. Although wingless integrated MMTV (Wnt)/β-catenin signaling plays an essential role in BBB formation and maintenance in healthy CNS, its role in BBB repair in neurologic diseases such as MS remains unclear. Using a Wnt/β-catenin reporter mouse and several downstream targets, we demonstrate that the Wnt/β-catenin pathway is up-regulated in CNS endothelial cells in both human MS and the mouse model experimental autoimmune encephalomyelitis (EAE). Increased Wnt/β-catenin activity in CNS blood vessels during EAE progression correlates with up-regulation of neuronal Wnt3 expression, as well as breakdown of endothelial cell junctions. Genetic inhibition of the Wnt/β-catenin pathway in CNS endothelium before disease onset exacerbates the clinical presentation of EAE, CD4 + T-cell infiltration into the CNS, and demyelination by increasing expression of vascular cell adhesion molecule-1 and the transcytosis protein Caveolin-1 and promoting endothelial transcytosis. However, Wnt signaling attenuation does not affect the progressive degradation of tight junction proteins or paracellular BBB leakage. These results suggest that reactivation of Wnt/β-catenin signaling in CNS vessels during EAE/MS partially restores functional BBB integrity and limits immune cell infiltration into the CNS.

Streptococcus pyogenes infections have been associated with two autoimmune diseases of the CNS: Sydenham's chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS). Despite the high frequency of pharyngeal streptococcus infections among children, only a small fraction develops SC or PANDAS. This suggests that several factors in combination are necessary to trigger autoimmune complications: specific S. pyogenes strains that induce a strong immune response toward the host nervous system; genetic susceptibility that predispose children toward an autoimmune response involving movement or tic symptoms; and multiple infections of the throat or tonsils that lead to a robust T h 17 cellular and humoral immune response when untreated. In this review, we summarize the evidence for each factor and propose that all must be met for the requisite neurovascular pathology and behavioral deficits found in SC/PANDAS.

The trillions of microbes that colonize our adult intestine are referred to as the gut microbiome (GMB). Functionally it behaves as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. While the relationship between the GMB and kidney stone disease (KSD) has not been investigated, dysbiosis of the GMB has been associated with diabetes, obesity and cardiovascular disease. In this pilot study we sought to identify unique changes in the GMB of kidney stone patients compared to patients without KSD. With an IRB-approved protocol we enrolled 29 patients into our pilot study. 23 patients were kidney stone formers and six were non-stone forming controls. Specimens were collected after a 6h fast and were flash frozen in dry ice and then stored at -80 °C. Microbiome: determination of bacterial abundance was by analysis of 16 s rRNA marker gene sequences using next generation sequencing. Sequencing of the GMB identified 178 bacterial genera. The five most abundant enterotypes within each group made up to greater than 50 % of the bacterial abundance identified. Bacteroides was 3.4 times more abundant in the KSD group as compared to control (34.9 vs 10.2 %; p = 0.001). Prevotella was 2.8 times more abundant in the control group as compared to the KSD group (34.7 vs 12.3 %; p = 0.005). In a multivariate analysis including age, gender, BMI, and DM, kidney stone disease remained an increased risk for high prevalence for Bacteroides (OR = 3.26, p = 0.033), whereas there was an inverse association with Prevotella (OR = 0.37, p = 0.043). There were no statistically significant differences in bacterial abundance levels for Bacteroides or Prevotella when comparing patients with and without DM, obesity (BMI >30), HTN or HLD. 11 kidney stone patients completed 24 h urine analysis at the time of this writing. Looking at the bacterial genuses with at least 4 % abundance in the kidney stone group, Eubacterium was inversely correlated with oxalate levels (r = -0.60, p < 0.06) and Escherichia trended to an inverse correlation with citrate (r = -0.56, p < 0.08). We also compared bacterial abundance between uric acid (UA) stone formers (n = 5) and non UA stone formers (n = 18) and found no significant difference between them. We identified two genus of bacteria in the GMB that had significant association with KSD. Interestingly, components of the 24-h urine appear to be correlated to bacterial abundance. These preliminary studies for the first time associate differences in the GMB with kidney stone formation. Further studies are warranted to evaluate the potential causative role of preexisting dysbiosis in kidney stone disease.

Importance: Prospective studies are needed to examine the temporal relationship between oral human papillomavirus (HPV) detection and risk of head and neck squamous cell carcinoma (HNSCC). Moreover, the oral cavity contains a wide spectrum of α-, β-, and γ-HPV types, but their association with risk of HNSCC is unknown., Objective: To prospectively examine associations between α-, β-, and γ-HPV detection in the oral cavity and incident HNSCC., Design: A nested case-control study was carried out among 96 650 participants, cancer free at baseline, with available mouthwash samples in 2 prospective cohort studies: (1) the American Cancer Society Cancer Prevention Study II Nutrition Cohort and (2) the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Incident cases of HNSCC (n = 132) were identified during an average 3.9 years of follow-up in both cohorts. Three controls per case (n = 396) were selected through incidence density sampling and matched on age, sex, race/ethnicity, and time since mouthwash collection., Methods: Through a next-generation sequencing assay, DNA from α-, β-, and γ-HPV types were detected. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs, adjusting for smoking history, alcohol consumption, and detection of HPV-16 for β- and γ-HPVs., Main Outcomes and Measures: Incident HNSCC, which includes cancers of the oropharynx, oral cavity, and larynx., Results: A total of 132 participants developed HNSCC during the follow-up period (103 men and 29 women; average age at baseline, 66.5 years). Oral HPV-16 detection was associated with incident HNSCC (OR, 7.1; 95% CI, 2.2-22.6), with positive association for oropharyngeal SCC (OR, 22.4; 95% CI, 1.8-276.7), but not for oral cavity (OR, 4.5; 95% CI, 0.6-34.7) or laryngeal SCCs (OR, 0.11; 95% CI, 0.01-834.80). Detection of β1-HPV-5 and β2-HPV-38 types, as well as γ-11 and γ-12 species, had ORs for HNSCC that ranged from 2.64 to 5.45 (P < .01 for all comparisons). Detection of β1-HPV-5 type was associated with oropharyngeal (OR, 7.42; 95% CI, 0.98-56.82; P = .054), oral cavity (OR, 5.34; 95% CI, 1.51-18.80; P = .01), and laryngeal SCCs (OR, 2.71; 95% CI, 1.00-7.43; P = .05), whereas γ11- and γ12-HPV species were associated with both oral cavity (OR, 7.47; 95% CI, 1.21-46.17; P = .03; and OR, 6.71; 95% CI, 1.47-30.75; P = .01, respectively) and laryngeal SCCs (OR, 7.49; 95% CI, 1.10-51.04; P = .04 and OR, 5.31; 95% CI, 1.13-24.95; P = .03, respectively)., Conclusions and Relevance: This study demonstrates that HPV-16 detection precedes the incidence of oropharyngeal SCC. Associations of other HPVs, including γ11- and γ12-HPV species and β1-HPV-5 type suggest a broader role for HPVs in HNSCC etiology.

Since 2012, US guidelines have recommended against prostate-specific antigen (PSA) screening for prostate cancer. However, evidence of screening benefit from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial and the European Randomized Study of Screening for Prostate Cancer has been inconsistent, due partly to differences in noncompliance and contamination. Using system dynamics modeling, we replicated the PLCO trial and extrapolated follow-up to 20 years. We then simulated 3 scenarios correcting for contamination in the PLCO control arm using Surveillance, Epidemiology, and End Results (SEER) incidence and survival data collected prior to the PSA screening era (scenario 1), SEER data collected during the PLCO trial period (1993-2001) (scenario 2), and data from the European trial's control arm (1991-2005) (scenario 3). In all scenarios, noncompliance was corrected using incidence and survival rates for men with screen-detected cancer in the PLCO screening arm. Scenarios 1 and 3 showed a benefit of PSA screening, with relative risks of 0.62 (95% confidence interval: 0.53, 0.72) and 0.70 (95% confidence interval: 0.59, 0.83) for cancer-specific mortality after 20 years, respectively. In scenario 2, however, there was no benefit of screening. This simulation showed that after correcting for noncompliance and contamination, there is potential benefit of PSA screening in reducing prostate cancer mortality. It also demonstrates the utility of system dynamics modeling for synthesizing epidemiologic evidence to inform public policy., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Bronchiolitis, the most common reason for hospitalization in children younger than 1 year in the United States, has no proven therapies effective beyond supportive care. We aimed to investigate the effect of nebulized 3% hypertonic saline (HS) compared with nebulized normal saline (NS) on length of stay (LOS) in infants hospitalized with bronchiolitis., Methods: We conducted a prospective, randomized, double-blind, controlled trial in an urban tertiary care children's hospital in 227 infants younger than 12 months old admitted with a diagnosis of bronchiolitis (190 completed the study); 113 infants were randomized to HS (93 completed the study), and 114 to NS (97 completed the study). Subjects received 4 mL nebulized 3% HS or 4 mL 0.9% NS every 4 hours from enrollment until hospital discharge. The primary outcome was median LOS. Secondary outcomes were total adverse events, subdivided as clinical worsening and readmissions., Results: Patient characteristics were similar in groups. In intention-to-treat analysis, median LOS (interquartile range) of HS and NS groups was 2.1 (1.2-4.6) vs 2.1 days (1.2-3.8), respectively, P = .73. We confirmed findings with per-protocol analysis, HS and NS groups with 2.0 (1.3-3.3) and 2.0 days (1.2-3.0), respectively, P = .96. Seven-day readmission rate for HS and NS groups were 4.3% and 3.1%, respectively, P = .77. Clinical worsening events were similar between groups (9% vs 8%, P = .97)., Conclusions: Among infants admitted to the hospital with bronchiolitis, treatment with nebulized 3% HS compared with NS had no difference in LOS or 7-day readmission rates., (Copyright © 2015 by the American Academy of Pediatrics.)

Purpose: Although overall there is a positive association between obesity and risk of prostate cancer (PrCa) recurrence, results of individual studies are somewhat inconsistent. We investigated whether the failure to exclude diabetics in prior studies could have increased the likelihood of conflicting results., Methods: A total of 610 PrCa patients who underwent radical prostatectomy between 2005 and 2012 were followed for recurrence, defined as a rise in serum PSA ≥ 0.2 ng/ml following surgery. Body mass index (BMI) and history of type 2 diabetes were documented prior to PrCa surgery. The analysis was conducted using Cox proportional hazard models., Results: Obesity (25.6 %) and diabetes (18.7 %) were common in this cohort. There were 87 (14.3 %) recurrence events during a median follow-up of 30.8 months after surgery among the 610 patients. When analyzed among all PrCa patients, no association was observed between BMI/obesity and PrCa recurrence. However, when analysis was limited to non-diabetics, obese men had a 2.27-fold increased risk (95 % CI 1.17-4.41) of PrCa recurrence relative to normal weight men, after adjusting for age and clinical/pathological tumor characteristics., Conclusions: This study found a greater than twofold association between obesity/BMI and PrCa recurrence in non-diabetics. We anticipated these results because the relationship between BMI/obesity and the biologic factors that may underlie the PrCa recurrence-BMI/obesity association, such as insulin, may be altered by the use of anti-diabetes medication or diminished beta-cell insulin production in advanced diabetes. Studies to further assess the molecular factors that explain the BMI/obesity-PrCa recurrence relationship are warranted.

The objective of this study was to identify the independent effect of visceral fat on urine constituent excretion in a stone forming population. Using a database of 382 kidney stone patients with available visceral fat quantification, we created multiple linear regression models predicting changes in urinary solutes based on visceral fat area and body mass-index, divided by gender. Chi-square tests were used to compare stone composition by body mass-index and visceral fat area. Visceral fat predicts increases in urinary creatinine, sodium, and volume in men, but only urinary phosphate in women. In women, total body mass-index does not appear to modify this effect, but in men it is more pronounced in overweight patients for creatinine and volume only. Elevated visceral fat is associated with increased probability of uric acid stone composition. Different fat compartments likely effect urine composition in different ways. This effect appears to be different in men and women. Understanding and quantifying the effects of different fat compartments is probably important to understanding the metabolism of urolithiasis.

Purpose: To analyze the perioperative outcomes and management considerations in patients with dialysis-dependent end-stage renal disease (ESRD) undergoing laparoscopic radical nephrectomy for renal-cell carcinoma (RCC)., Methods: There were 224 consecutive laparoscopic radical nephrectomies reviewed. Of those, 37 patients with ESRD were identified and compared with 187 patients with sporadic RCC. Evaluable parameters included age, sex, race, side of surgery, medical comorbidities, body mass index, American Society of Anesthesiologist (ASA) scoring, and age adjusted Charlson Comorbidity Index. All complications occurring intraoperatively and within the first 30 days were classified as per the Clavien classification system. Presurgical workup and transplant considerations were evaluated. Demographic and clinical characteristics were compared using Student t tests and chi-square tests for categoric variables., Results: Compared with non-ESRD patients, those with ESRD were younger and had smaller tumors. ASA was significantly higher in the ESRD group (P<0.001). Mean blood loss was similar between ESRD patients and non-ESRD patients. Overall complication rates were higher in patients with ESRD. Pathologic characteristics of ESRD renal masses included a higher proportion of papillary RCC., Conclusion: Patients with RCC associated with ESRD tend to have a higher ASA class and lower grade tumors. In addition, this population is at increased risk of surgical complications and more likely to need transfusions. Careful preoperative preparation and intraoperative anesthetic management are crucial to minimize patient morbidity and improve outcomes.

Background: Men of African descent have the highest incidence and mortality rates of prostate cancer (PrCa) worldwide. Notably, PrCa is increasing in Africa with Nigerian men being mostly affected. Thus, it is important to understand risk factors for PrCa in Nigeria and build capacity for cancer research. The goals of this study were to determine the feasibility of conducting an epidemiological study of PrCa and to obtain preliminary data on risk factors for PrCa in Nigeria., Methods: A case-control study (50 cases/50 controls) was conducted at the University College Hospital (UCH) in Ibadan, Nigeria, between October 2011 and December 2012. Men aged 40 to 80 years were approached for the study and asked to provide informed consent and complete the research protocol. Logistic regression models were used to examine associations between demographic, social and lifestyle characteristics and risk of PrCa., Results: The participation rate among cases and controls was 98% and 93%, respectively. All participants completed a questionnaire and 99% (50 cases/49 controls) provided blood samples. Cases had a median serum diagnostic PSA of 73 ng/ml, and 38% had a Gleason score 8-10 tumor. Family history of PrCa was associated with a 4.9-fold increased risk of PrCa (95% CI 1.0 - 24.8). There were statistically significant inverse associations between PrCa and height, weight and waist circumference, but there was no association with body mass index (kg/m(2)). There were no associations between other socio-demographic and lifestyle characteristics and PrCa risk., Conclusion: This feasibility study demonstrated the ability to ascertain and recruit participants at UCH and collect epidemiological, clinical and biospecimen data. Our results highlighted the advanced clinical characteristics of PrCa in Nigerian men, and that family history of PrCa and some anthropometric factors were associated with PrCa risk in this population. However, larger studies are needed to better understand the epidemiological risk factors of PrCa in Nigeria.

Background: Evidence suggests that the risk of breast and prostate cancer is increased among those with a family history of the same disease and particularly among first-degree relatives. However, less is known about the relationship between breast and prostate cancer within families and particularly among minority populations., Methods: Analyses of participants in the Women's Health Initiative observational cohort who were free of breast cancer at the time of their baseline examination were conducted. Subjects were followed for breast cancer through August 31, 2009. A Cox proportional hazards regression modeling approach was used to estimate the risk of breast cancer associated with a family history of prostate cancer, breast cancer, and both among first-degree relatives., Results: There were 78,171 eligible participants, and 3506 breast cancer cases were diagnosed during the study period. A family history of prostate cancer was associated with a modest increase in breast cancer risk after adjustments for confounders (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.02-1.26). In a separate analysis examining the joint impact of both cancers, a family history of both breast and prostate cancer was associated with a 78% increase in breast cancer risk (aHR, 1.78; 95% CI, 1.45-2.19). Risk estimates associated with a family history of both breast and prostate cancer were higher among African American women (aHR, 2.34; 95% CI, 1.09-5.02) versus white women (aHR, 1.66; 95% CI, 1.33-2.08)., Conclusions: These findings suggest that prostate cancer diagnosed among first-degree family members increases a woman's risk of developing breast cancer. Future studies are needed to determine the relative contributions of genes and a shared environment to the risk for both cancers., (© 2015 American Cancer Society.)

Importance: Patients with Parkinson disease (PD) who harbor LRRK2 G2019S mutations may have increased risks of nonskin cancers. However, the results have been inconsistent across studies., Objectives: To analyze pooled data from 5 centers to further examine the association between LRRK2 G2019S mutation and cancer among patients with PD and to explore factors that could explain discrepancies., Design, Setting, and Participants: Clinical, demographic, and genotyping data as well as cancer outcomes were pooled from 1549 patients with PD recruited across 5 movement disorders clinics located in Europe, Israel, and the United States. Associations between LRRK2 G2019S mutation and the outcomes were examined using mixed-effects logistic regression models to estimate odds ratios (ORs) and 95% CIs. Models were adjusted for age and ethnicity (Ashkenazi Jewish vs others) as fixed effects and study center as a random effect., Main Outcomes and Measures: All cancers combined, nonskin cancers, smoking-related cancers, hormone-related cancers, and other types of cancer., Results: The overall prevalence of the LRRK2 G2019S mutation was 11.4% among all patients with PD. Mutation carriers were younger at PD diagnosis and more likely to be women (53.1%) and of Ashkenazi Jewish descent (76.8%) in comparison with individuals who were not mutation carriers. The LRRK2 G2019S mutation carriers had statistically significant increased risks for nonskin cancers (OR, 1.62; 95% CI, 1.04-2.52), hormone-related cancers (OR, 1.87; 95% CI, 1.07-3.26) and breast cancer (OR, 2.34; 95% CI, 1.05-5.22) in comparison with noncarriers. There were no associations with other cancers. There were no major statistically significant differences in the results when the data were stratified by Ashkenazi Jewish ethnicity; however, there was some evidence of heterogeneity across centers., Conclusions and Relevance: This multinational study from 5 centers demonstrates that LRRK2 G2019S mutation carriers have an overall increased risk of cancer, especially for hormone-related cancer and breast cancer in women. Larger prospective cohorts or family-based studies investigating associations between LRRK2 mutations and cancer among patients with PD are warranted to better understand the underlying genetic susceptibility between PD and hormone-related cancers.

The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5' of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53-0.67, P=9 × 10(-18)), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25. The association is stronger for oestrogen receptor-negative disease (OR 0.34, 95% CI 0.21-0.54) than oestrogen receptor-positive disease (OR 0.63, 95% CI 0.49-0.80; P heterogeneity=0.01) and is also associated with mammographic breast density, a strong risk factor for breast cancer (P=0.001). rs140068132 is located within several transcription factor-binding sites and electrophoretic mobility shift assays with MCF-7 nuclear protein demonstrate differential binding of the G/A alleles at this locus. These results highlight the importance of conducting research in diverse populations.

Purpose: Obesity is a risk factor for metabolic syndrome and urolithiasis, particularly uric acid stones. As estimated by visceral fat area, visceral obesity is a more specific measure of the risk of metabolic syndrome than body mass index. We investigated the effects of visceral fat area and other metabolic factors on uric acid stone formation in patients treated with percutaneous nephrolithotomy., Materials and Methods: We retrospectively reviewed the records of 269 patients who underwent percutaneous nephrolithotomy. Visceral fat area was measured in each patient on a CT axial slice at the umbilical level using the Aquarius iNtuition fat analysis tool. Analysis was performed to determine the effect of visceral fat area and other comorbidities on uric acid stone formation., Results: Of the 269 patients analyzed there was no difference in baseline comorbidities between uric acid and nonuric acid stone formers. Patients with uric acid stones had a significantly higher mean visceral fat area (209.3 vs 161.9 cm², p = 0.001), and rates of hypertension (67.4% vs 47.3%) and coronary artery disease (14.3% vs 4.6%, each p = 0.011). On logistic regression analysis hypertension (OR 2.16, 95% CI 1.05-4.45, p = 0.04) and a high visceral fat area (OR 3.64, 95% CI 1.22-10.85, p = 0.02) were independent risk factors for uric acid stones., Conclusions: As a marker of visceral obesity, visceral fat area contributes to the risk of metabolic syndrome and urolithiasis. Uric acid stone formers showed a significantly higher hypertension rate and mean visceral fat area, which were independent risk factors for uric acid urolithiasis. Evaluating these characteristics in stone formers may facilitate a tailored metabolic assessment and treatment plan., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Statins are a class of cholesterol-lowering drugs that affect many intracellular pathways that may have implications for chemoprevention against cancer. Epidemiologic data on statins and breast cancer are conflicting. We analyzed updated data from the Women's Health Initiative (WHI) to assess the relationship between statins and breast cancer risk., Methods: The population included 154,587 postmenopausal women ages 50 to 79 years, with 7,430 pathologically confirmed cases of breast cancer identified over an average of 10.8 (SD, 3.3) years. Information on statins was collected at baseline and years one, three, six, and nine. Self- and interviewer-administered questionnaires were used to collect information on risk factors. Cox proportional hazards regression was used to calculate HRs with 95% confidence intervals (CI) to evaluate the relationship between statin use and cancer risk. Statistical tests were two-sided., Results: Statins were used by 11,584 (7.5%) women at baseline. The annualized rate of breast cancer was 0.42% among statin users and 0.42% among nonusers. The multivariable adjusted HR of breast cancer for users versus nonusers was 0.94 (95% CI, 0.83-1.06). In the multivariable-adjusted, time-dependent model, the HR for simvastatin was 0.87 (95% CI, 0.71-1.07). There was no significant trend by overall duration of use (P value for trend 0.68). There was no effect of tumor stage, grade, or hormone receptor status., Conclusion: Overall, statins were not associated with breast cancer risk., Impact: Our study is one of the largest prospective observational studies on this topic, and substantially adds to the literature suggesting no relationship between statins and breast cancer risk.

Objective: To assess the relationship between visceral obesity and perioperative parameters in patients undergoing laparoscopic or robotic-assisted partial nephrectomy., Methods: We retrospectively reviewed the medical records of 118 patients who underwent minimally invasive partial nephrectomy. On preoperative imaging, perinephric, visceral, and subcutaneous fat were measured. Higher estimated blood loss, complications, and warm ischemia time were used as surrogates of increased operation difficulty. We examined the association between the 3 groups of patients (ie low, medium, and high fat) with demographic and clinical characteristics. Multivariate analysis was performed to determine whether various measurements of obesity adversely affected surgical outcomes and complexity., Results: No statistically significant differences were found between perioperative parameters and either perinephric, visceral, or subcutaneous fat. There was no association between changes in renal function and different fat groups. Multivariate analysis for estimated blood loss, complication rates, and warm ischemia time adjusted for age, race, sex, nephrometry score, Charlson comorbidities score, and other fat types, failed to demonstrate any significant differences. Increasing perinephric fat content was associated with higher visceral (P <.0005), but not subcutaneous fat (P = .55). Hypertension was associated with perinephric (P = .02) and visceral (P = .04), but not subcutaneous obesity (P = .08). Neither Charlson comorbidity nor American Society of Anesthesiologists scores showed any significant association with different fat types., Conclusion: Individual patterns of obesity, namely subcutaneous, visceral, and perinephric, do not increase surgical complexity for minimally invasive partial nephrectomy by experienced surgeons. Furthermore, this operation can be performed safely with comparable complications and outcomes in moderately obese patients without compromising renal function., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Multiplex assays are available to measure an array of circulating chemokines, soluble cytokine receptors and growth factors. However, there is limited information regarding whether these analytes are suitable for large-scale epidemiological studies to assess their relationships with chronic diseases, including cancer., Methods: We examined detectability, assay repeatability, and 3-year within-subject reproducibility of plasma levels of 25 chemokines and 11 soluble receptors of cytokines and growth factors selected from the Human Millipore Panels. Plasma samples were obtained from 36 men (average age 62 years) and 17 women (average age 32 years) who participated in two epidemiological studies. Inter-assay and within-subject reproducibility were assessed by intraclass correlation coefficients (ICC)., Results: All analytes, except lymphotactin (47% detectability), were detectable in >90% of plasma samples. Inter-assay reproducibility for all analytes in 36 men tested three times on separate days were good to excellent (ICCs: 0.71-1.00). Within-subject reproducibility in 17 women sampled three times in three years were excellent (ICC ≥ 0.75) for five chemokines (eotaxin, fractalkine, 6Ckine, eotaxin 3, and SDF-1α+β) and three soluble receptors (sIL-1R2, sIL-4R and sVEGFR2); ICCs were fair to good (0.4 ≤ ICC < 0.75) for 15 chemokines and eight soluble receptors. However, five chemokines (GRO, IP-10, MIP-1β, BCA-1, and MIP-3α) had ICC < 0.4, suggesting biological variability., Conclusion: Multiplex assays for plasma levels of selected chemokines and soluble receptors showed good to excellent assay detectability and repeatability. Most analytes also had good 3-year within-subject reproducibility, indicating that a single measurement of these analytes may be used to assess biomarker-disease associations.

Purpose: The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed., Methods: Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (<0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition., Results: When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers., Conclusions: This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis.

Background: Genome-wide association studies (GWAS) have identified multiple SNPs associated with prostate cancer (PrCa). Population isolates may have different sets of risk alleles for PrCa constituting unique population and individual risk profiles., Methods: To test this hypothesis, associations between 31 GWAS SNPs of PrCa were examined among 979 PrCa cases and 1,251 controls of Ashkenazic descent using logistic regression. We also investigated risks by age at diagnosis, pathological features of PrCa, and family history of cancer. Moreover, we examined associations between cumulative number of risk alleles and PrCa and assessed the utility of risk alleles in PrCa risk prediction by comparing the area under the curve (AUC) for different logistic models., Results: Of the 31 genotyped SNPs, 8 were associated with PrCa at p ≤ 0.002 (corrected p-value threshold) with odds ratios (ORs) ranging from 1.22 to 1.42 per risk allele. Four SNPs were associated with aggressive PrCa, while three other SNPs showed potential interactions for PrCa by family history of PrCa (rs8102476; 19q13), lung cancer (rs17021918; 4q22), and breast cancer (rs10896449; 11q13). Men in the highest vs. lowest quartile of cumulative number of risk alleles had ORs of 3.70 (95% CI 2.76-4.97); 3.76 (95% CI 2.57-5.50), and 5.20 (95% CI 2.94-9.19) for overall PrCa, aggressive cancer and younger age at diagnosis, respectively. The addition of cumulative risk alleles to the model containing age at diagnosis and family history of PrCa yielded a slightly higher AUC (0.69 vs. 0.64)., Conclusion: These data define a set of risk alleles associated with PrCa in men of Ashkenazic descent and indicate possible genetic differences for PrCa between populations of European and Ashkenazic ancestry. Use of genetic markers might provide an opportunity to identify men at highest risk for younger age of onset PrCa; however, their clinical utility in identifying men at highest risk for aggressive cancer remains limited.

Unlabelled: What's known on the subject? and What does the study add? In addition to a higher prevalence and biological aggressiveness of prostate cancer, African-Americans tend towards narrower pelvises than Caucasians resulting in a potentially more difficult surgical dissection doing radical prostatectomy and increased positive surgical margins. In this study, there was no difference in urinary or sexual HRQL or overall satisfaction between African-Americans and Caucasians 2 years after radical prostatectomy, suggesting that the potential technical challenges of a narrower pelvis do not translate into poorer outcomes for African-Americans., Objective: To determine if any differences exist in postoperative health-related quality-of-life (HRQL) outcomes, e.g. erectile function and continence, after radical prostatectomy (RP) in African-American (AA) vs Caucasian-American (CA) men., Patients and Methods: Between October 2000 and July 2008, 1338 CA and 56 AA men underwent open RP by a single surgeon and signed informed consent to participate in a prospective longitudinal outcomes study. The American Urological Association Symptom Score (AUA-SS) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and a global assessment of satisfaction were self-administered at baseline and after RP 24 months. Urinary, sexual, and satisfaction outcomes were compared at 24 months., Results: AA men had significantly higher rates of hypertension and diabetes. There were no other significant baseline differences in age, co-morbidities, body mass index, phosphodiesterase type 5 inhibitor use, preoperative prostate-specific antigen level, AUA-SS, and UCLA-PCI scores. There were no differences in the percentage of men undergoing nerve-sparing procedures, estimated blood loss, transfusion rates, or complication rates between the groups. At 24 months after RP the mean UCLA-PCI urinary and sexual function and bother scores and global satisfaction scores were similar between the groups., Conclusion: AA and CA men experience no significant differences in urinary and sexual HRQL or overall satisfaction after open RP when performed by a single experienced surgeon., (© 2012 BJU INTERNATIONAL.)

Purpose: The effect of statins on prostate cancer recurrence has been investigated in several studies with inconsistent results. We investigated whether statins were associated with biochemical recurrence in a large cohort of men after radical prostatectomy. We also performed a meta-analysis of existing studies., Materials and Methods: A total of 1,446 patients who underwent radical prostatectomy at New York University were followed a median of 57 months for biochemical recurrence events. Baseline demographic and clinical characteristics were compared between 437 statin users and 1,009 nonusers. Kaplan-Meier curves and Cox models were used to examine biochemical recurrence-free survival by statin use. A meta-analysis was performed with data from our cohort and 5 published studies using the random effects model., Results: Statin users were slightly older and more likely to have diabetes (p <0.01). They were similar to nonusers in race and body mass index. Although preoperative prostate specific antigen and tumor stage were similar between the 2 groups, the proportion of patients with pathological Gleason score 7-10 tumors was slightly higher among statin users (p = 0.03). The biochemical recurrence-free survival rate was 87.4% and 89.0% for statin users and nonusers, respectively, at the end of followup (log rank p = 0.26). Overall biochemical recurrence was not associated with statin use (HR 1.15, 95% CI 0.82-1.61). Results were similar when patients were stratified by D'Amico low and intermediate or high risk groups. Meta-analysis revealed no overall association between statins and biochemical recurrence (pooled HR 1.00, 95% CI 0.80-1.19)., Conclusions: Our findings are consistent with the results of the meta-analysis, which indicated that preoperative statin use does not impact the overall risk of biochemical recurrence., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Genetic variation on the Y chromosome has not been convincingly implicated in prostate cancer risk. To comprehensively analyze the role of inherited Y chromosome variation in prostate cancer risk in individuals of European ancestry, we genotyped 34 binary Y chromosome markers in 3,995 prostate cancer cases and 3,815 control subjects drawn from four studies. In this set, we identified nominally significant association between a rare haplogroup, E1b1b1c, and prostate cancer in stage I (P = 0.012, OR = 0.51; 95% confidence interval 0.30-0.87). Population substructure of E1b1b1c carriers suggested Ashkenazi Jewish ancestry, prompting a replication phase in individuals of both European and Ashkenazi Jewish ancestry. The association was not significant for prostate cancer overall in studies of either Ashkenazi Jewish (1,686 cases and 1,597 control subjects) or European (686 cases and 734 control subjects) ancestry (P(meta) = 0.078), but a meta-analysis of stage I and II studies revealed a nominally significant association with prostate cancer risk (P(meta) = 0.010, OR = 0.77; 95% confidence interval 0.62-0.94). Comparing haplogroup frequencies between studies, we noted strong similarities between those conducted in the US and France, in which the majority of men carried R1 haplogroups, resembling Northwestern European populations. On the other hand, Finns had a remarkably different haplogroup distribution with a preponderance of N1c and I1 haplogroups. In summary, our results suggest that inherited Y chromosome variation plays a limited role in prostate cancer etiology in European populations but warrant follow-up in additional large and well characterized studies of multiple ethnic backgrounds.

Unlabelled: Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? It is generally accepted in the medical community that total and intra-operative blood loss after RALP is significantly lower in comparison with ORRP. This has led to speculation that less bleeding results in better visualization of the operative field resulting in superior potency and continence. Blood loss (BL) during ORRP does not adversely impact clinical and functional outcomes irrespective of how BL is defined. Thus, the lower BL associated with RALP would not be expected to improve functional or oncological outcomes., Objective: To determine the short- and long-term impact of blood loss (BL) on clinical, oncological and functional outcomes as well as complication rates after an open radical retropubic prostatectomy (ORRP)., Patients and Methods: Between 2000 and 2008, 1567 men who underwent an ORRP participated in our prospective longitudinal outcomes study. Haematocrit (Hct) levels, transfusion rates, BL and complications were recorded prospectively. Validated, self-administered quality-of-life (QoL) questionnaires were completed at baseline, 3, 6 and 12 months and yearly thereafter. Urinary function and erectile dysfunction were assessed using AUA Symptom Score and the UCLA Prostate Cancer Index and analysis of variance (anova)/chi-square tests were used to compare clinical, BL, biochemical recurrence (BCR) and QoL outcomes amongst the three groups for continuous/categorical variables., Results: The mean estimated BL was 742.7 (45 to 3500) mL and 5.4% and 3.8% received an autologous (AU) or allogeneic (AL) blood transfusions, respectively. The average baseline, induction, postoperative and discharge Hct was 43.8%, 48.3%, 35.7% and 34.1%, respectively. The estimated BL and the rate of change of Hct correlated moderately (r=0.41, P<0.0001). Tertiles of BL were based on the difference between induction and discharge Hct (Delta 1) and the average Delta 1 for Groups 1, 2 and 3 were 7.9%, 12.7% and 17.2%, respectively. Intra-operative, early/delayed complications, length of hospital stay (LoS), SM surgical margins status, anastomotic stricture and BCR were not statistically different (P<0.001) and the mean AUASS, UCLA Prostate Cancer urinary bother scores, urinary function scores, sexual bother/function scores at 24 months were similar amongst all tertiles (P>0.05)., Conclusions: BL during ORRP does not adversely impact clinical and functional outcomes irrespective of how BL is defined. Thus, the lower BL associated with robotic-assisted laparoscopic prostatectomy (RALP) in and of itself would not be expected to improve functional or oncological outcomes., (© 2011 BJU INTERNATIONAL.)

Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case-control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 × 10(-6), 1.6 × 10(-5), 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 × 10(-5)), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H.pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer.

Purpose: We assessed the predictive effect of prostate specific antigen velocity for men with a minimum of 3 pre-biopsy prostate specific antigen measurements in a racially diverse population., Materials and Methods: We identified 795 patients who underwent 3 or more prostate specific antigen tests before prostate biopsy. Prostate specific antigen velocity was calculated by linear regression and used to assess associations with the risk of prostate cancer overall and of high grade prostate cancer (Gleason score 7-10). We created ROC curves and determined the AUC for several models, including only prostate specific antigen velocity or the last prostate specific antigen measurement before biopsy, to predict prostate cancer and high grade prostate cancer., Results: The risk of prostate cancer and high grade prostate cancer increased linearly with increasing prostate specific antigen velocity quartiles (each p trend<0.001). Older patients were more likely to be diagnosed with prostate cancer, given the same prostate specific antigen velocity. In black and Hispanic patients there were strong linear associations between increasing prostate specific antigen velocity and the risk of prostate cancer overall and high grade prostate cancer. ROC curves incorporating prostate specific antigen velocity to predict prostate cancer and high grade prostate cancer varied significantly by race. The AUC of models in black and Hispanic patients was significantly higher than in white patients (0.62 and 0.64, respectively, vs 0.47, p=0.03)., Conclusions: Prostate specific antigen velocity is a significant predictor of prostate cancer and high grade prostate cancer in men with 3 or more prostate specific antigen tests before prostate biopsy. Black and Hispanic patients appear to be at increased risk for prostate cancer at higher prostate specific antigen velocity, as are men older than 60 years. Further studies should confirm these results and create age and race specific guidelines to assess prostate specific antigen velocity., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the outcomes of our robotic-assisted pyeloplasty series for primary ureteropelvic junction obstruction (UPJO) and compare them with our series of robotic-assisted pyeloplasty for secondary UPJO. The repair of secondary UPJO can pose additional challenges to surgeons. Robotic assistance could aid in these repairs., Methods: Using an institutional review board-approved database, we reviewed 119 consecutive patients who had undergone robotic-assisted laparoscopic pyeloplasty at our institution during an 8-year period (May 2002 to February 2010). Data were collected in a combined retrospective and prospective manner. The patients were stratified into primary repair and secondary repair for the primary analysis. The patients were also stratified into those with stones and those without stones for the secondary analysis. We compared the demographic, operative, postoperative, and radiographic outcomes. Student's t test and Pearson's chi-square correlation were used for statistical analysis of continuous and categorical variables, respectively., Results: Of the original 119 patients, data were available for 117. Of the 117 patients, 97 had undergone primary pyeloplasty repair and 20 had undergone secondary pyleloplasty repair. Radiographic data were available for 84 patients with primary repair and 17 patients with secondary repair. The radiographic success rate was 96.1% and 94.1%, respectively. No statistically significant differences were found in the patient demographics, operative data, or postoperative or radiographic outcomes for the primary analysis. Additionally, no differences were found in the outcomes for patients with concomitant stone disease., Conclusion: These data represent the largest single-center report of its kind. These data strongly suggest that robotic-assisted laparoscopic pyeloplasty is a safe and durable option for secondary UPJO repair., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To examine the impact of short-term preoperative utilization of erythropoietin-stimulating agents (ESAs) on biochemical recurrence (BCR)-free survival rates after open radical retropubic prostatectomy (ORRP) in light of the fact that the risk/benefit of ESAs has recently been questioned by the Food and Drug Administration (FDA) after reports showing a decreased survival., Patients and Methods: From 2000 to 2008, 1567 patients underwent ORRP and 97.5% of these signed informed consent to participate in the New York University Prospective and Longitudinal Outcomes Study. Of the remaining 1528 patients, 1317 (86%) received preoperative ESA (group 1) and 211 (14%) did not (group 2). Patients were also classified as having low-, intermediate- or high-risk disease based on D'Amico risk categories. Kaplan-Meier survival curves and Cox's proportional hazard models were used to estimate BCR-free survival by ESA treatment., Results: A significant difference was observed for BCR-free survival between the low- and intermediate/high-risk groups. There were no statistically significant differences between groups 1 and 2 for BCR-free survival in the entire study populations and within risk groups. In addition, Cox regression models showed no statistically significant differences in BCR-free survival according to preoperative ESA administration in the entire cohort as well as among the low- and intermediate/high-risk groups., Conclusions: The short-term use of ESAs as a preoperative blood management strategy for patients undergoing ORRP has no clinically relevant adverse effects on the biology of prostate cancer. The present study supports the use of these agents before the procedure in patients undergoing surgery for localized disease., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: Exposure to endotoxin has been consistently associated with a reduced risk of lung cancer. However, there is a paucity of information regarding temporal aspects of this relationship. The objective of this study was to investigate the associations between contiguous windows of endotoxin exposure and risk of lung cancer., Methods: Data were reanalyzed from a case-cohort study (602 cases, 3,038 subcohort) of female textile workers in Shanghai, China. Cumulative endotoxin exposure was partitioned into two windows: ≥20 and <20 years before risk. Exposure-response relations were examined using categorical and non-linear (semi-parametric) models, accounting for confounding by previous exposure windows., Results: There was an inverse trend of decreasing risk of lung cancer associated with increasing levels of endotoxin exposure ≥20 years before risk (p trend = 0.02). Women in the highest two categories of cumulative exposures had hazard ratios of 0.78 (95% CI 0.60-1.03) and 0.77 (95% CI 0.58-1.02) for lung cancer, respectively, in comparison with unexposed textile workers. There was, however, a weaker association and not statistically significant between lung cancer and endotoxin exposure accumulated in the more recent window (<20 years before risk)., Conclusion: Results provide further evidence that endotoxin exposure that occurred 20 years or more before risk confers the strongest protection against lung cancer, indicating a possible early anti-carcinogenic effect. Further studies are needed to better understand the underlying biological mechanisms for this effect.

Prostate cancer disparities have been reported in men of African descent who show the highest incidence, mortality, compared with other ethnic groups. Few studies have explored the genetic and environmental factors for prostate cancer in men of African ancestry. The glutathione-S-transferases family conjugates carcinogens before their excretion and is expressed in prostate tissue. This study addressed the role of GSTM1 and GSTT1 deletions on prostate cancer risk in populations of African descent. This multi-institutional case-control study gathered data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database, the African-Caribbean Cancer Consortium (AC3) and Men of African Descent and Carcinoma of the Prostate Consortium (MADCaP). The analysis included 10 studies (1715 cases and 2363 controls), five in African-Americans, three in African-Caribbean and two in African men. Both the GSTM1 and the GSTT1 deletions showed significant inverse associations with prostate cancer [odds ratio (OR): 0.90, 95% confidence interval (CI) 0.83-0.97 and OR 0.88, 95% CI: 0.82-0.96, respectively]. The association was restricted to Caribbean and African populations. A significant positive association was observed between GSTM1 deletion and prostate cancer in smokers in African-American studies (OR: 1.28, 95% CI: 1.01-1.56), whereas a reduced risk was observed in never-smokers (OR: 0.66, 95% CI: 0.46-0.95). The risk of prostate cancer increased across quartiles of pack-years among subjects carrying the deletion of GSTM1 but not among subjects carrying a functional GSTM1. Gene-environment interaction between smoking and GSTM1 may be involved in the etiology of prostate cancer in populations of African descent.

Background: Prostate cancer is a disease with a complex etiology. Oxidative stress has been implicated in its pathogenesis; however, few prospective studies have investigated the association between an oxidative stress/balance score and risk of prostate cancer., Methods: We investigated associations between an oxidative balance score, calculated as the summation of individual scores obtained from five pro-oxidative and eight anti-oxidative exposures, as well as each individual constituent of the score and risks of prostate cancer overall, and by clinical characteristics, in a case-cohort study (661 cases and 1864 subcohort) nested within the Canadian Study of Diet, Lifestyle, and Health cohort. Men in the lowest quintiles of each pro-oxidant exposure received a score of four (the highest score), while those in the highest quintile received a score of zero (the lowest score). In contrast, scoring for all anti-oxidants was performed in the opposite way. Total oxidative balance score was calculated by summating all individual scores of pro- and anti-oxidative variables, with higher values indicating a higher antioxidant status., Results: The average oxidative balance score was similar between prostate cancer cases and men in the subcohort: 25.2 and 25.3, respectively. There was no association between oxidative balance score and overall risk of prostate cancer with hazard ratios (HRs) of 1.00, 1.02, 1.03, 0.97 and 1.01 for increasing quintiles of the score (p-trend=0.71). There were also no associations for non-advanced or advanced disease, or when analysis was restricted to incident cases that arose after two years of follow-up (n=508). In general constituents of the score were not associated with prostate cancer, except for red meat intake (HR=1.44; 95%CI 1.06-1.95 comparing Q5 vs. Q1) and lycopene (HRs of 0.7-0.8 for increasing quintiles)., Conclusion: Our findings do not support an association between oxidative balance score and risks of overall prostate cancer or advanced disease., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background and Purpose: Membranous urethral length is one of several factors that can influence return of continence after radical prostatectomy. Using our robot-assisted laparoscopic prostatectomy (RALP) database, we assessed which preoperative (with endorectal coil MRI [eMRI]) and intraoperative anatomic measurements correlate with return to urinary continence (no pads) and continence quality of life (CQOL) as determined by the International Consultation on Incontinence Questionnaire (ICIQ) score., Patients and Methods: A total of 75 patients who underwent RALP and eMRI by a single surgeon were analyzed. To emulate the distal continence zone intraoperatively, stretched urethral length (distance from the perineal membrane to the prostate apex on stretch) and cut urethral length (urethral stump length) were individually measured and recorded after apical dissection. Preoperative International Prostate Symptom Scores (IPSS) were recorded. Univariate and multivariate Cox regression analysis were performed to determine the association between MRI-measured and intraoperative urethral lengths and return to continence as well as CQOL., Results: None of the urethral measurements as determined by eMRI correlated with continence or ICIQ scores. On multivariate analysis, only membranous urethral length on eMRI approached significance with respect to ICIQ (P=0.07). On multivariate analysis controlling for preoperative age, body mass index, IPSS score, and gland size, both stretched and cut urethral length correlated with decreased time to continence (P=0.03 and P=0.04 respectively)., Conclusion: Longer stretched and cut urethral lengths appear to correlate with faster return to a pad-free state. Attention to maximal preservation of the distal continence mechanism is important for optimal continence outcomes after RALP.