Elizabeth N. Kuhn, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 6, 2013
The esophagus is a muscular tube that connects the mouth to the stomach. It moves the food we swallow from our mouths to our stomachs, where it can be digested. The esophagus is typically about 25 cm (10 inches) long and meets the stomach at what is called the gastroesophageal junction (GE junction). At the GE junction, there is a circular muscle that wraps around the esophagus called the lower esophageal sphincter. This is not a muscle that we can control voluntarily - normally, it opens only to let food from the esophagus into the stomach or during vomiting. The lower esophageal sphincter muscle prevents food and acid in the stomach from coming back up into the esophagus.
The lining of the esophagus is called the mucosa, which protects the esophagus from things that might cause damage, like stomach acid. The cells that make up the mucosa are replaced at a high rate to compensate for the damage that occurs during everyday eating. The cells in the mucosa are arranged as flat cells in many layers (called "stratified squamous epithelium").
Barrett's esophagus occurs when the cells that make up the lining of the esophagus change as a result of frequent damage, and do not grow back normally. This change, called metaplasia, predisposes to cancer development. Instead of being composed of flat cells in many layers ("stratified squamous epithelium"), there is a single layer of tall-shaped cells ("columnar epithelium"), which are considered pre-cancerous.
Barrett's esophagus is more common in developed countries with predominantly Caucasian populations (eg. United States, Europe). Specifically, Barrett's esophagus is most common among white males who have a history of chronic gastro-esophageal reflux symptoms. In Western countries, about 10-15% of people have Barrett's esophagus.
The most common cause of Barrett's esophagus is gastroesophageal reflux disease (GERD), or heartburn. When a person has GERD, acid from the stomach splashes up into the esophagus causing repeated damage to the lining of the esophagus. Many people with Barrett's esophagus have a history of heartburn or acid regurgitation lasting at least 10 years. Some people, however, develop Barrett's esophagus without ever having any reflux symptoms. Anyone with GERD is at risk for Barrett's esophagus and we don't currently know what makes some people with GERD develop Barrett's esophagus while others don't. The following risk factors for Barrett's esophagus are well-established: age >50 years, male gender, white (Caucasian) race, chronic GERD, hiatal hernia (a condition where part of the stomach protrudes into the chest, increasing acid reflux into the esophagus), and obesity. Though less common and less well-studied, bulimia with vomiting also increases the risk of Barrett's esophagus due to damage to the esophagus from repeated vomiting.
Screening for Barrett's esophagus is controversial because it is very difficult to predict who has Barrett's esophagus prior to endoscopy. In addition, there is a lack of evidence to guide screening, and the screening is invasive and expensive. Currently, the American Gastroenterological Association does not recommend screening the general population for Barrett's esophagus. Screening for high-risk people with several risk factors for Barrett's esophagus should be individualized.
People with Barrett's esophagus have a higher risk of developing cancer of the esophagus, though overall the risk to an individual of cancer or death is low. There are two kinds of esophageal cancer based on how the cancer cells appear under the microscope: squamous cell cancer and adenocarcinoma. Barrett's esophagus increases one's risk of esophageal adenocarcinoma up to 55 times compared to the general population. For that reason, Barrett's esophagus is considered a "premalignant" disease, meaning that while it is not cancer, it can become cancer.
Based on a number of studies in the United States, the risk of developing adenocarcinoma if you have Barrett's esophagus is approximately 0.5% per year. In other words, if you had a group of 200 people with Barrett's esophagus, one person would be diagnosed with cancer of the esophagus each year. Men have a higher risk of developing esophageal adenocarcinoma than women for reasons that we don't fully understand. Though the overall risk of developing esophageal adenocarcinoma is low, Barrett's esophagus is still very important clinically because treatments for Barrett's are more successful than treatments for esophageal cancer. See more information about esophageal cancer.
Barrett's esophagus is diagnosed by upper endoscopy with multiple biopsies. During endoscopy, a flexible tube with a camera on the end is passed through the esophagus into the stomach and duodenum, the first part of the small intestine. Upper endoscopy allows your doctor to look at the insides of these organs and detect ulcers, abnormal growths, and other conditions like Barrett's esophagus. Barrett's esophagus is typically described as a "salmon-colored" patch at the end of the esophagus. During endoscopy, multiple biopsies are taken and the tissue is examined under a microscope to confirm the presence of metaplasia, the changes in cell type of the esophageal mucosa necessary to make a diagnosis of Barrett's. Biopsies are also important to ensure that there is no cancer present. All biopsies should be examined by two or more pathologists, preferably at least one of whom is an expert in pathology of the esophagus.
The severity of Barrett's esophagus is described in two ways:
Dysplasia describes an abnormal appearance of cells under a microscope - more highly abnormal cells are more likely to become cancer. Dysplasia can be either low-grade or high-grade, and exists on the following spectrum: metaplasia à low-grade dysplasia à high-grade dysplasia à invasive cancer. The Prague C&M Criteria are a set of standardized rules that allow physicians to determine how severe Barrett's esophagus is. The "C" refers to Circumferential extent of disease and the "M" refers to Maximum extent of disease. The "C" is determined by measuring the distance from the GE junction to the highest location where metaplasia is present around the entire circumference of the esophagus. The "M" is the distance from the GE junction to the highest location of metaplasia. The higher the Prague C&M numbers (eg. C3 M5), the more severe the Barrett's esophagus and the higher the risk of developing cancer.
Treatment in people with Barrett's esophagus is targeted toward reducing acid reflux. There are several medications, such as proton pump inhibitors (eg. omeprazole, Prilosec) and H2-blockers (eg. ranitidine, Zantac). These medications work by decreasing the amount of acid that is produced in the stomach; generally, proton pump inhibitors are more effective than H2-blockers. There are also several anti-reflux surgeries, such as fundoplication, that can be performed to control reflux. Unfortunately, there are no randomized, controlled studies that show that either acid suppression therapy or anti-reflux surgery reduce the risk of developing cancer of the esophagus. Therefore, the American College of Gastroenterology does not recommend antireflux surgery or high dose proton pump inhibitors for the prevention of adenocarcinoma of the esophagus – though these therapies can and should still be used to treat symptoms of chronic reflux.
In recent years, there has been interest in whether aspirin can reduce the risk of esophageal adenocarcinoma. There are two very large ongoing clinical trials, the AspECT and WASP trials, which are investigating whether aspirin combined with a proton pump inhibitor reduces the risk of developing esophageal adenocarcinoma. The results of the studies are not yet available, but so far, the combined treatment appears to be a safe one. Currently it is recommended that all people with other indications to use aspirin (eg. Heart disease, diabetes, stroke) should do so, but aspirin should not be used solely to prevent esophageal cancer.
Right now, the most important measures patients with Barrett's esophagus can take are acid suppression and routine screening for esophageal cancer. Surveillance is performed by endoscopy with biopsy and how often a patient needs endoscopy is based on how severe their disease is. The American College of Gastroenterology and American Gastroenterological Association recommend the following treatment and surveillance guidelines:
Eradication therapy is recommended for people with high-grade dysplasia, with the goal of permanently eliminating all abnormal areas of mucosa. There are several different strategies for endoscopic eradication including radiofrequency ablation, photodynamic therapy, or endoscopic mucosal resection. Radiofrequency ablation uses electricity and heat to damage cells, and is targeted toward the abnormal areas. Clinical trials show that radiofrequency ablation eliminates Barrett's esophagus in 80-90% of patients and lasts at least five years. Photodynamic therapy uses a chemical called a photosensitizer and a light source. The photosensitizer is applied to tissues or areas the clinician wants to eradicate; when light is directed at those cells, the reaction between light and the photosensitizer causes cell death. Endoscopic mucosal resection is a procedure where part of the lining of the esophagus is surgically removed and is recommended especially when the suspicion for cancer is high. Most patients (70-80%) can be successfully treated with endoscopic eradication therapy. Those patients who do not respond to eradication therapy should be referred to a center that specializes in the treatment of esophageal and stomach cancer for possible treatment with surgical removal of the entire esophagus.
This article serves as an introduction to Barrett's esophagus. More information about esophageal cancer and its treatment can be found OncoLink. As always, talk to your doctor if you are concerned about Barrett's esophagus or esophageal cancer.
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