Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

<p>Abstract</p> <p>Background</p> <p>In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence.</p> <p>Method</p> <p>The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at <url>http://www.seleblat.org.</url> Patients are randomly assigned to selenium yeast (200 μg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study.</p> <p>Design</p> <p>The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial.</p> <p>Discussion</p> <p>This is the first report on a selenium randomized trial in bladder cancer patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00729287">NCT00729287</a></p

How Broad Should Gram-Negative Coverage Be for Febrile Parenteral Nutrition Dependent Short Bowel Syndrome Patients?

ABSTRACT: Broader spectrum Gram-negative antibiotics are commonly utilized empirically for central line-associated bloodstream infections (CLABSI) in febrile short bowel syndrome (SBS) patients receiving home parenteral nutrition compared to those used empirically for inpatient-acquired CLABSI. This analysis reports 57 CLABSI in 22 patients with SBS admitted from the community and 78 inpatient-acquired CLABSI in 76 patients over a 5-year period. Proportional Gram-negative CLABSI was similar between the SBS and inpatient-acquired cohorts (43.8% vs42.3%, respectively, P  = 0.78). 1.8% and 10.3% (P = 0.125) of Gram-negative CLABSI were non-susceptible to ceftriaxone and 0% and 3.8% (P = 0.52) were non-susceptible to ceftazidime in the SBS and inpatient-acquired cohorts, respectively. In the SBS cohort, home ethanol lock therapy and prior culture results impacted Gramnegative pathogen distribution. Broader empiric Gram-negative coverage for CLABSI among SBS patients compared to inpatients is unnecessary. Third-generation cephalosporins represent appropriate empiric Gramnegative agents for febrile SBS patients presenting from the community to our institution.http://deepblue.lib.umich.edu/bitstream/2027.42/192638/2/How Broad Should Gram-Negative Coverage Be for Febrile Parenteral Nutrition Dependent Short Bowel Syndrome Patients.pdfPublished versio

Postdiagnostic Statin Use and the Risk of Lethal Prostate Cancer in the Health Professionals Follow-up Study

BACKGROUND: Observational studies suggest potential chemopreventive benefits of statins on prostate cancer outcomes, but data on the impact of postdiagnostic use are sparse. METHODS: We examined the association of postdiagnostic statin use and risk of lethal prostate cancer (metastases or prostate cancer death, N = 242) among 3,949 men diagnosed with localized prostate cancer from the Health Professionals Follow-Up Study between 1992 and 2008 and followed through 2010 (33,302 person years). We used Cox proportional hazards regression models to estimate relative risks and 95% confidence intervals (CI), adjusting for age, time period, time from diagnosis to questionnaire, body mass index, vigorous physical activity, smoking, aspirin use, clinical stage, PSA at diagnosis, Gleason score, primary treatment, and comorbidities. RESULTS: We found no statistically significant association between postdiagnostic current use of statins or duration of statin usage and the outcome of lethal prostate cancer [N = 242 cases; multivariate HR = 0.97 (95% CI, 0.72–1.31) for current use yes/no; HR = 0.85 (95% CI, 0.59–1.22) for 1 to 5 years of use, 0.96 (95% CI, 0.66–1.38) for 6+ years of use vs. never use]. CONCLUSIONS: We observed little evidence that statin usage after diagnosis of localized prostate cancer reduces risk of progression to metastatic disease or prostate cancer–specific death. IMPACT: These results do not support statins as a chemopreventive agent for prostate cancer progression

Abstract 1856: DNA damage and repair markers (H2AX and RAD51) improve accuracy of prostate cancer diagnosis and improve identification of aggressive disease

Abstract Background: Prostate biopsy is the gold standard test for diagnosing prostate cancer. However, due to the sampling error involved, it has low accuracy. Using markers associated with DNA damage and the concept of field effect, this study attempts to improve the diagnostic accuracy of prostate biopsies in men at high risk for this disease. Methods: Data were obtained from men participating in the Negative Biopsy Trial, a randomized multicenter phase 3 chemoprevention trial designed to investigate the effects of selenium supplementation on prostate cancer incidence in men who were at high risk for prostate cancer (PSA (prostate specific antigen) &amp;gt; 4ng/ml &amp;/or PSA velocity (rate of PSA change over time) &amp;gt; 0.75ng/ml/yr &amp;/or positive digital rectal examination) and had a negative prostate biopsy. 699 men were randomized to three treatment arms (placebo, 200ug Se/d, 400ug Se/d) and were followed every 6 months for up to five years. During the course of the study, 73 subjects were diagnosed with prostate cancer on repeat biopsy. For the current study, prostate biopsy samples from 73 subjects and 144 matched controls were stained for RAD51 and H2AX, markers of DNA repair, using immunohistochemistry techniques. Image analysis was conducted using ScanScope and Spectrum software from Aperio Technologies (Vista, California), which provided percentage of positive nuclei. Statistical analysis was conducted using Stata12 statistical software (Statacorp, College station, Texas). Results: Subjects diagnosed with prostate cancer, as compared to controls, demonstrated higher expression levels of both H2AX (mean(SD), 33.8(17.7) and 19.4(14.5)) as well as RAD51 (55.8(24.1) and (44.7(26.5)). As compared to the model containing baseline PSA, age and race (k1), the model containing RAD51 and H2AX data in addition to the data included in k1 showed improved positive predictive value, negative predictive value and area under the curve (70%, 78.9%, 0.77 and 80%, 87.06%, 0.90 respectively, p= 0.025). The above also holds true when data from subjects diagnosed with low grade disease are compared with those having high grade disease (100%, 80%, 0.72 and 100%, 85%, 0.82, p=0.07). Conclusions: Results of this study indicate that DNA damage markers may improve diagnostic accuracy for prostate cancer and also for aggressive disease in both men at high risk, and men diagnosed with prostate cancer. Citation Format: Amit M. Algotar, Anne E. Cress, Raymond B. Nagle, Dan Drinkwitz, Naran S. Lodhia, Patricia A. Thompson, Steven P. Stratton. DNA damage and repair markers (H2AX and RAD51) improve accuracy of prostate cancer diagnosis and improve identification of aggressive disease. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1856. doi:10.1158/1538-7445.AM2014-1856</jats:p