Barrett esophagus

Abstract

T he incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the western world and accounts for 2% of all cancer-related deaths. The precursor lesion for EAC is Barrett esophagus (BE), which is strongly associated with gastresophageal reflux disease. A major limitation to the study of EAC has been the absence of tractable and genetically modifiable preclinical models of BE. A mouse model of BE and EAC that resembles human disease could provide novel insights into the origins and molecular pathogenesis of BE. In addition, validated animal models could help stratify BE patients given the limited predictive power of current standard endoscopic measures and clinical assessment. Here, we review the findings from recently developed mouse models of BE and EAC and their impact on clinical decision making, surveillance programs and therapeutic options. The data, taken together, suggest potential origins of BE from the gastric cardia, a role of bile acid and hypergatrinemia for carcinogenesis, a growing importance for columnar-like epithelium and a critical role for Notch signaling.

Gastrointestinal stem cells in health and disease: from flies to humans

“…These lesions are associated with aberrant cell proliferation and differentiation, which eventually leads to loss of tissue homeostasis. A tremendous number of clinical studies have focused on the epidemiology and pathogenesis of intestinal metaplasia and dysplasia in humans ( Correa and Houghton, 2007 ; Harpaz and Polydorides, 2010 ; Kapoor et al, 2015 ), and studies in animal models, including in mice and flies, have greatly expanded our knowledge of the mechanisms that cause these lesions at the cellular and molecular level ( Li et al, 2013a ; Liu et al, 2013 ; Mari et al, 2014 ; Quante et al, 2012a ). In the closing sections of this Review, we discuss these studies particularly in the context of our emerging understanding of how intrinsic and extrinsic factors cause GI epithelial dysfunction, and how dysregulation of GI stem cells is related to these lesions.…”

The Rapid Rise in Gastroesophageal Junction Tumors: Is Inflammation of the Gastric Cardia the Underwater Iceberg?

“…1,16–19 Bile acids change the inflammatory microenvironment 1,2 and potentially alter the microbiome. Thus, bile acid reflux could be another piece to the puzzle, which could help to explain the observed junctional inflammation (Figure 1).…”

A Summary of the 2016 James W. Freston Conference of the American Gastroenterological Association: Intestinal Metaplasia in the Esophagus and Stomach: Origins, Differences, Similarities and Significance

“…The rodent esophagus joins stomach at the junction between squamous-lined forestomach and distal glandular stomach, and the squamocolumnar junction has a distinctive “first fundic gland” containing cells that express stem cell markers including LGR5 and DCLK-1. 45,46 …”