Effect of ondansetron, a 5-HT(3) receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study

Background and aims: There are no available effective therapies for fatigue associated with chronic hepatitis C (CHC). The serotonin antagonist ondansetron has been shown to be effective in the chronic fatigue syndrome. In this randomised, placebo controlled, double blind trial, we investigated the effect of orally administered ondansetron on fatigue in CHC. Methods: Thirty six patients with CHC were included if fatigue was their predominant symptom and they scored more than 4 on a visual analogue scale (0–10). During the study, fatigue and depression were measured on days 0, 15, 30, and 60 using a validated self report questionnaire (fatigue impact scale and Beck depression inventory). Patients were randomised to receive ondansetron tablets 4 mg twice daily or placebo for one month followed by an additional four weeks of observation. Results: Fatigue score was 85.4 (28.2) and 98.2 (26.9) in the ondansetron and placebo groups, respectively (NS). Ondansetron significantly reduced the fatigue score with more than 30% improvement on day 15 (57.1 (38.9); p<0.01), day 30 (54.5 (37.6); p<0.01), and day 60 (60.8 (37.3); p<0.01) whereas placebo did not. Overall, the reduction in fatigue was significantly higher with ondansetron compared with placebo (ANOVA for repeated measurements) for the whole follow up period (p = 0.03) or for the treatment period only (p = 0.04). Ondansetron also significantly reduced depression scores. Conclusions: The 5-hydroxytryptamine receptor type 3 antagonist ondansetron had a significant positive effect on fatigue in CHC. These observations support the concept that fatigue involves serotoninergic pathways and may encourage further evaluations of the efficacy of ondansetron on fatigue in chronic liver diseases

Human papillomavirus does not play a role in the Barrett esophagus: a French cohort

International audienceThe role of human papillomavirus (HPV) in Barrett's esophagus (BE) has been examined but remains unclear. The purpose of the study is to dispute the connection between HPV and BE in a prospective case-control study. Biopsies were performed above and inside the Barrett's segment for BE patients and in the distal third of the esophagus for control patients for histological interpretation and for virological analysis. Biopsies for virological analysis were placed in a virus transport medium and immediately frozen in liquid nitrogen. Virological analysis involved real-time PCR using the SyBr® green protocol with modified SPF10 general primers. A total of 180 patients (119 control and 61 BE, respectively) were included. In BE patients, 31, 18, and 12 patients had, respectively, no dysplasia, low-grade dysplasia, and high grade dysplasia. Overall, nine were found to be HPV positive: five were control patients and four BE patients. HPV positive status was not associated with BE. No factors were associated with HPV, in particular the degree of BE dysplasia. HPV infection appears unlikely to be significant in the etiology of BE compared with control patients. (ClinicalTrials.gov, Number NCT02549053)

Overweight is associated to a better prognosis in metastatic colorectal cancer: A pooled analysis of FFCD trials

IF 7.191 (2017)International audienceBACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI <18.5). Interaction tests were performed between BMI effect and sex, age and the addition of antiangiogenics to chemotherapy.RESULTS:The rate of BMI ≥25 patients was 41.5%, ranging from 37.6% (1991-1999 period) to 41.5% (2000-2006 period) and 44.8% (2007-2013 period). Comparison of overweight patients versus normal BMI range patients revealed a significant improvement of median overall survival (OS) (18.5 versus 16.3 months, HR = 0.88 [0.80-0.98] p = 0.02) and objective response rate (ORR) (42% versus 36% OR = 1.23 [1.01-1.50] p = 0.04) but a comparable median progression-free survival (PFS) (7.8 versus 7.2 months, HR = 0.96 [0.87-1.05] p = 0.35). Subgroup analyses revealed that overweight was significantly associated with better OS in men. OS and PFS were significantly shorter in thin patients.CONCLUSION:Overweight patients had a prolonged OS compared with normal weight patients with mCRC. The association of overweight with better OS was only observed in men. The pejorative prognosis of BMI <18.5 was confirmed.Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserve