Upper Gastrointestinal Tract
The Role of Bile Reflux in Barrett’s Esophagus Lisa Cassani, MD1
and Michael F Vaezi, MD, PhD, MSc (Epi)2
1. Resident in Internal Medicine; 2. Professor of Medicine and Clinical Director, Department of Gastroenterology and Hepatology, and Director, Clinical Research and Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center
Abstract
Acid and bile reflux occur together in patients with gastroesophageal reflux disease (GERD). The differential role of each refluxate in the development of Barrett’s esophagus, a complication of GERD, has historically been difficult to establish due to lack of a gold standard diagnostic testing. The advent of Bilitec™, a bile-monitoring device, and more recently, impedance monitoring, has suggested a synergistic role for acid and bile in the development of Barrett’s esophagus. The mucosal damage in the esophagus is more due to this synergism of gastroduodenal contents and less the bile reflux alone. Studies have suggested that although bile reflux alone may cause symptoms such as nausea, vomiting, or regurgitation, it rarely causes mucosal damage unless combined with acid reflux. Proton pump inhibitor therapy thus reduces acid reflux, which by default reduces the toxicity of refluxate to the esophageal mucosa.
Keywords Bile reflux, acid reflux, Barrett’s esophagus, duodenogastroesophageal reflux
Disclosure: Lisa Cassani, MD, has no conflicts of interest to declare. Michael F Vaezi, MD, PhD, MSc (Epi), has received research funds from Takeda. Received: May 24, 2011 Accepted: June 14, 2011 Citation: US Gastroenterology & Hepatology Review, 2011;7(1):12–6 Correspondence: Michael F Vaezi, MD, PhD, MSc (Epi), Professor of Medicine and Clinical Director, Department of Gastroenterology and Hepatology, and Director, Clinical Research and Center for Swallowing and Esophageal Disorders, Vanderbilt University Medical Center, 1660 TVC, Nashville, TN 37232-5280. E:
Michael.vaezi@
vanderbilt.edu
Barrett’s esophagus is a metaplastic process where the normal squamous epithelium of the esophagus is replaced with columnar epithelium of the intestine. This condition is associated with gastroesophageal reflux disease (GERD) and often represents the end-stage of reflux esophagitis. This change in epithelium is of clinical importance because it is associated with increased risk for esophageal adenocarcinoma.
Although GERD appears to be common in the general population, with approximately 10 to 20% of people experiencing reflux symptoms weekly, Barrett’s esophagus is seen in only 10% of those with GERD.1,2 The prevalence of Barrett’s esophagus itself depends on the population studied, with lower prevalence reported in the Asian literature compared with developed countries and even higher still in those who have chronic reflux symptoms.3,4
According to population-based cohort studies, the incidence of adenocarcinoma of the esophagus has rapidly increased over the last 30–40 years. However, the risk for developing adenocarcinoma if a person has Barrett’s esophagus is still low at 0.5% per patient year.4
Speculation of the progenitor cell leading to Barrett’s esophagus continues to be a topic of interest. Potential theories include progenitor cells residing in the esophageal epithelium, bone-marrow-derived stem cells, or less likely, migration of columnar cells from the gastric cardia. The most accepted theory at this time is that Barrett’s esophagus
12
develops from multipotent progenitor cells present in the basal layer that differentiate into glandular cells after severe mucosal injury.4–6
However,
the pathophysiologic reasons for why and how the progenitor cells are stimulated is uncertain. The role of gastroduodenal reflux in this process is under continued evaluation and in this section we will highlight our current understanding of the role of acid and bile in Barrett’s esophagus.
Role of Acid Bile in Barrett’s Esophagus Excessive gastroesophageal reflux often produces symptoms and the complication rate including esophagitis, strictures, or Barrett’s esophagus for these patients reaches approximately 50%.7
The gastric
contents predisposing patients to the development of esophageal symptoms, mucosal injury, and the potential for Barrett’s esophagus and adenocarcinoma include hydrochloric acid and pepsin.7,8
Although,
gastric acid and pepsin are well accepted as contributors to the development of Barrett’s esophagus, its development in achlorhydric and postgastrectomy patients suggests bile acids and pancreatic enzymes may play a role as well.
Duodenogastroesophageal reflux (DGER) is the reflux of duodenal contents, including bile and pancreatic secretions, into the stomach and esophagus. Reflux into the stomach normally occurs in the post-prandial state and at night. However, when excessive, DGER can be associated with complications similar to GERD, including gastritis, ulcers, dyspepsia, and esophagitis. DGER was previously referred to as bile reflux and
© TOUCH BRIEFINGS 2011
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