Proanthocyanidins mitigate bile acid-induced changes in GSTT2 levels in a panel of racially diverse patient-derived primary esophageal cell cultures.

Persistent and symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux disease (GERD), is the strongest risk factor for esophageal adenocarcinoma (EAC). Despite similar rates of GERD and other risk factors across racial groups, EAC progression disproportionately impacts Caucasians. We recently reported that elevated tissue levels of the detoxification enzyme GSTT2 in the esophagi of Blacks compared to Caucasians may contribute protection. Herein, we extend our research to investigate whether cranberry proanthocyanidins (C-PAC) mitigate bile acid-induced damage and GSTT2 levels utilizing a racially diverse panel of patient-derived primary esophageal cultures. We have shown that C-PACs mitigate reflux-induced DNA damage through GSTT2 upregulation in a rat esophageal reflux model, but whether effects are recapitulated in humans or differentially based on race remains unknown. We isolated normal primary esophageal cells from Black and Caucasian patients and assessed GSTT2 protein levels and cellular viability following exposure to a bile acid cocktail with and without C-PAC treatment. Constitutive GSTT2 levels were significantly elevated in Black (2.9-fold) compared to Caucasian patients, as were GSTT2 levels in Black patients with GERD. C-PAC treatment induced GSTT2 levels 1.6-fold in primary normal esophageal cells. GSTT2 induction by C-PAC was greatest in cells with constitutively low GSTT2 expression. Overall, C-PAC mitigated bile-induced reductions of GSTT2 and subsequent loss of cell viability regardless of basal GSTT2 expression or race. These data support that C-PAC may be a safe efficacious agent to promote epithelial fitness through GSTT2 induction and in turn protect against bile acid-induced esophageal injury.

Predictors of Use of Monitored Anesthesia Care for Outpatient Gastrointestinal Endoscopy in a Capitated Payment System.

BACKGROUND & AIMS: Use of monitored anesthesia care (MAC) for gastrointestinal endoscopy has increased in the Veterans Health Administration (VHA) as in fee-for-service environments, despite the absence of financial incentives. We investigated factors associated with use of MAC in an integrated health care delivery system with a capitated payment model. METHODS: We performed a retrospective cohort study using multilevel logistic regression, with MAC use modeled as a function of procedure year, patient- and provider-level factors, and facility effects. We collected data from 2,091,590 veterans who underwent outpatient esophagogastroduodenoscopy and/or colonoscopy during fiscal years 2000-2013 at 133 facilities. RESULTS: The adjusted rate of MAC use in the VHA increased 17% per year (odds ratio for increase, 1.17; 95% confidence interval, 1.09-1.27) from fiscal year 2000 through 2013. The most rapid increase occurred starting in 2011. VHA use of MAC was associated with patient-level factors that included obesity, obstructive sleep apnea, higher comorbidity, and use of prescription opioids and/or benzodiazepines, although the magnitude of these effects was small. Provider-level and facility factors were also associated with use of MAC, although again the magnitude of these associations was small. Unmeasured facility-level effects had the greatest effect on the trend of MAC use. CONCLUSIONS: In a retrospective study of veterans who underwent outpatient esophagogastroduodenoscopy and/or colonoscopy from fiscal year 2000 through 2013, we found that even in a capitated system, patient factors are only weakly associated with use of MAC. Facility-level effects are the most prominent factor influencing increasing use of MAC. Future studies should focus on better defining the role of MAC and facility and organizational factors that affect choice of endoscopic sedation. It will also be important to align resources and incentives to promote appropriate allocation of MAC based on clinically meaningful patient factors.

Shedding some light on the etiology of adenocarcinomas of the esophagus and gastric cardia.

Environmental and behavioral factors likely have large roles in the etiology of adenocarcinomas of the esophagus and gastroesophageal junction. Prior ecological analyses suggest a protective effect of exposure to UV radiation for these cancers. But such analyses are prone to particular forms of bias. In this issue of The American Journal of Gastroenterology, new individual-level data is presented supporting such an association. Presumably, this is mediated by vitamin D, but definitive evidence is lacking. Supplementation with vitamin D aimed at preventing these cancers cannot be recommended at this time. More study regarding the role of vitamin D in Barrett's esophagus and these cancers are needed.