Risk Factors for Progression of Barrett\u2019s Esophagus to High Grade Dysplasia and Esophageal Adenocarcinoma

Swetha Kambhampati,Stephen J Meltzer,Brandon Luber,Hao Wang,Alan H Tieu

doi:10.1038/s41598-020-61874-7

Abstract

Barrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Methods of identifying BE patients at high risk for progression to high-grade dysplasia (HGD) or EAC are needed to improve outcomes and identify who will benefit most from intensive surveillance or ablative therapy. Clinical predictors of BE progression to HGD or EAC are poorly understood, with multiple contradictory studies. We performed a retrospective study which included 460 patients at Johns Hopkins Hospital who underwent at least 2 upper endoscopies 6 months apart showing biopsy-documented BE between 1992 and 2013. Patients with EAC or HGD at the initial endoscopy were excluded. Demographic, clinicopathological, and endoscopic data were collected. Univariate and multivariate Cox proportional hazards analyses with time to progression to HGD and EAC were performed. Among 460 patients included in the study, 132 BE patients developed HGD and 62 developed EAC. Significant EAC risk factors included age, abdominal obesity, caffeine intake, and the presence of HGD. Risk factors for HGD or EAC included age, caffeine intake, and low-grade dysplasia while colonic adenomas trended towards significance. Notably, a history of statin or SSRI usage reduced the risk of EAC or HGD by 49% or 61%, respectively. Our study validated several known and identified several novel risk factors, including a history of colonic adenomas or caffeine usage. Low-grade dysplasia was a risk factor for progression but various endoscopic characteristics were not, suggesting that screening strategies should focus on histology instead. We identified SSRIs as a new potentially chemoprotective medication.

Highlights

Barrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC)
Significant histologic risk factors for progression included low-grade dysplasia (LGD). In this retrospective study of 460 patients with histologic BE, we applied multivariate regression model to identify clinical, epidemiologic, endoscopic, and histologic risk factors for progression BE to high-grade dysplasia (HGD) or EAC
Regarding obesity, we found that central abdominal obesity was a significant risk factor for both HGD and EAC, but not increased body mass index (BMI), suggesting that fat distribution primarily contributed to this risk

Summary

Introduction

Barrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Significant EAC risk factors included age, abdominal obesity, caffeine intake, and the presence of HGD. Risk factors for HGD or EAC included age, caffeine intake, and low-grade dysplasia while colonic adenomas trended towards significance. Low-grade dysplasia was a risk factor for progression but various endoscopic characteristics were not, suggesting that screening strategies should focus on histology instead. Since most BE patients will not develop EAC, and given the risk and expense of endoscopic surveillance, understanding risk factors for BE progression is important to effectively focus resources on high-risk BE patients, allowing patient stratification and enabling tailored surveillance and therapy. The aims of our study are to comprehensively assess clinical, epidemiological, endoscopic, and histopathologic risk and protective factors for the progression of BE to either HGD or EAC. We reason that a clearer understanding of these factors would help optimize surveillance, since it would enable better resource allocation to surveil patients with positive, high risk factors, promoting more efficient and earlier detection of HGD and EAC

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