Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking.

Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20-30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption.

Presence of small sessile serrated polyps increases rate of advanced neoplasia upon surveillance compared with isolated low-risk tubular adenomas.

BACKGROUND AND AIMS: The U.S. Multi-Society Task Force (USMSTF) stratifies patients with sessile serrated polyps (SSPs) without cytologic dysplasia of <10 mm in size as at low risk for metachronous advanced neoplasia and recommends management similar to low-risk conventional tubular adenomas. Evidence supporting the recommended surveillance interval for these low-risk SSPs is limited. We aimed to assess rates of metachronous advanced neoplasia based on the presence of an initial low-risk SSP compared with isolated low-risk tubular adenomas. METHODS: Colonoscopy data were retrieved for 2260 patients found to have an adenoma or SSP on pathology records between 2005 and 2011 at an academic medical center. The 788 patients who met study design criteria were stratified into 4 groups based on the presence of a high- or low-risk adenoma (HRA or LRA) and of a synchronous SSP on initial colonoscopy. The rates of advanced neoplasia at surveillance colonoscopy were then compared between groups. RESULTS: The rate of advanced neoplasia at surveillance in the LRA inclusive of SSP group (12/66, 18.2%) was greater than in the LRA without any SSP group (29/370, 7.8%; P = .019). The rate of advanced neoplasia at surveillance in patients with isolated low-risk SSP (10/56, 17.9%) remained significantly greater than those with isolated low-risk tubular adenomas (29/370, 7.8%; P = .024). The rate of advanced neoplasia upon surveillance in the LRA inclusive of SSP group (18.2%) was comparable with the rate observed in the index HRA without any SSP group (15.9%) (40/252, P = .709). CONCLUSIONS: The rate of advanced neoplasia upon surveillance in patients with initial low-risk SSPs is higher than in patients with initial isolated low-risk tubular adenomas and more similar to patients with initial high-risk tubular adenomas. These findings suggest that the rate of metachronous advanced neoplasia in patients with what are considered by USMSTF as "low-risk" SSPs is higher than in those without SSPs. Therefore, a surveillance interval that accounts for the presence of SSPs even in small lesions without cytologic dysplasia should be considered.