What is acid reflux?

Patients with long-segment Barrett esophagus have an estimated 30 to 125 times increased risk of developing esophageal cancer compared with the general population. Early studies suggested that the median cancer incidence was 1 per 100 patient-years of follow-up, but more recent studies with longer follow-up suggest a lower cancer rate of 1 per 200 to 250 patient-years. This is an annual incidence of approximately 0.5%, with about 500 cases of adenocarcinoma diagnosed annually. However, since the early 1980s, the incidence of squamous cell carcinoma has stayed constant, whereas the incidence of adenocarcinoma of the esophagus and esophagogastric junction has risen fivefold—a growth rate exceeding that of any other cancer. Currently, adenocarcinoma accounts for more than half of all esophageal cancers in the United States. Despite this cancer risk, most patients with Barrett esophagus die of unrelated causes. More than 90% of patients who develop cancer present with symptoms caused by the tumor itself and are unaware of their antecedent Barrett esophagus. Epidemiologic data suggest that the mean interval from developing Barrett esophagus to evolution to cancer may be 20 to 30 years.

Management of patients with Barretts metaplasia has two aspects: treating the underlying GERD and managing the risk of adenocarcinoma of the esophagus. The principles for treating peptic esophagitis and controlling symptoms in Barretts metaplasia are the same as for uncomplicated GERD with the proviso that because it is associated with extreme esophageal acid exposure, it will likely require more intensive treatment. In general, mucosal damage and symptoms can be controlled with proton pump inhibitor therapy, but surgery may be needed, or even desirable, in refractory cases.
On the basis of in vitro and in vivo cell proliferation studies reporting increased cell proliferation and decreased differentiation in tissue exposed to acid, some authorities believe that complete acid suppression is desirable in therapy for Barretts metaplasia. However, there is no clinical evidence that aggressive antisecretory therapy or antireflux surgery prevents the occurrence of adenocarcinoma or causes regression of intestinal metaplasia. Proton pump inhibitor therapy has proved to be of no avail in reversing metaplasia or preventing adenocarcinoma. Thus, the available data support titrating therapy to control symptoms and treat esophagitis, irrespective of the presence of Barretts metaplasia.

Barrett esophagus is suspected at endoscopy and is confirmed by biopsy and histological examination. The columnar epithelium of the stomach is reddish pink, and the junction between the glossy white squamous mucosa and the columnar mucosa (Z-line) is normally found at the lower end of the tubular esophagus, just above the proximal folds of a hiatal hernia, if present. In Barrett esophagus, the distal esophagus is lined with columnar epithelium, extending upward for a variable distance, often 3 to 10 cm, but occasionally involving most of the esophagus.The proximal margin may be horizontal, or there may be irregular, often tongue-shaped upward extensions of columnar mucosa. Some patients have pale islands of regenerative or residual squamous epithelium, whereas others have punched-out benign ulcers in the columnar area. Strictures and esophagitis may be seen at the new squamocolumnar junction. The endoscopist should especially look for evidence of adenocarcinoma, such as nodularity or masses.

The characteristic histological finding in Barrett esophagus is a distinctive specialized intestinal epithelium. This is a glandular epithelium with mucin-type cells and the distinguishing presence of goblet cells. These are easily seen on hematoxylin and eosin–stained sections and can be demonstrated more prominently in sections stained with Alcian blue. It occupies most or all of the columnar-lined area and is the type of epithelium in which adenocarcinoma arises. Other types of epithelia seen with Barrett esophagus include gastric fundic and cardia-type epithelia, but these alone do not make the diagnosis of Barrett esophagus, nor are they associated with adenocarcinoma.

Currently, there is some controversy over the classification of Barrett esophagus. The classical or long-segment Barrett esophagus requires at least 3 cm of esophagus to be lined with columnar epithelium. This is the best-studied subset of Barrett esophagus, with traditional demographic features and a definite increased risk of becoming adenocarcinoma. Short-segment Barrett esophagus refers to shorter lengths or tongues of columnar epithelium, less than 3 cm, in the distal esophagus, with intestinal metaplasia on biopsy. This entity is three to five times more common than the long-segment variant, but, based on anecdotal reports, the risk of cancer appears to be lower. Intestinal metaplasia at the esophagogastric junction refers to microscopic findings on biopsy but no visible columnar epithelium in the esophagus at endoscopy. This finding has been reported in 10% to 32% of biopsies from unselected patients, many of whom have no reflux symptoms. The percentage of woman and African Americans is also higher with this lesion than with either long- or short-segment Barrett esophagus. The cause is controversial; some investigators suggest that this is the earliest form of GERD, whereas others believe these changes are secondary to H pylori infection. Cancer risk is minimal, if it exists at all.

In some patients with GERD, the squamous epithelium of the distal esophagus is replaced by specialized columnar epithelium, resembling that of the intestine and containing goblet cells. Although Dr. Norman Barrett thought this lesion was a congenitally shortened esophagus, studies consistently show that these patients have severe GERD with low LES pressures, poor esophageal motility, large hiatal hernias, and extensive acid and bile reflux. Furthermore, most patients have had chronic reflux symptoms for at least 10 years. Animal experiment show that, if the mucosal lining of the distal esophagus is excised in the setting of free acid reflux, columnar epithelium will regenerate in the area previously occupied by squamous epithelium. If reflux is controlled, the mucosal lining will regenerate with squamous epithelium. Pluripotential stem cells derived from the stratified squamous epithelium are the origin of the specialized columnar epithelium.

Barrett esophagus was once considered an uncommon condition, but estimates of its frequency at autopsy (1 in 57 to 1 in 105 cases), on general endoscopy survey (1 in 100 cases) and on endoscopic surveys of patients with GERD (10 in 100 to 15 in 100 cases), indicate that it is not uncommon, and it affects nearly 700,000 adults in the United States. An autopsy series from Olmsted County, Minnesota found that most cases of Barrett esophagus go undetected during life and thus are not accessible for cancer surveillance programs. Barrett esophagus is principally a disorder of white men; it is three times more frequent in men than in women and is rare in African Americans and Asians. It is found predominantly in middle-aged and older adults; the mean age at diagnosis is approximately 55 years, but it has been reported in children older than 5 years of age. The prevalence of Barrett esophagus increases with age, paralleling that of reflux esophagitis, but the length of the columnar-lined segment remains remarkably stable, even over years of endoscopic follow-up. This finding suggests that it arises rapidly in the susceptible reflux damaged esophagus and early in the course of disease. Families have been reported with multiple members having Barrett esophagus, some with cancer affecting more than one generation. Although the columnar-lined esophagus in itself does not cause symptoms, most patients complain of heartburn and regurgitations. Approximately 25% of patients with Barrett esophagus discovered at endoscopy have no esophageal symptoms.