Diagnosis

Although more than 60 years have passed since Barrett published his original treatise on the condition that now bears his name, authorities still dispute the diagnostic criteria for Barrett’s esophagus. The conceptual definition proposed in the introduction does not translate readily into clear-cut diagnostic criteria, in part because it is not clear which of the multiple columnar cell types that can be found in Barrett’s esophagus have a malignant predisposition.

In 1976, Paull and colleagues reported that patients with Barrett’s esophagus could have up to three types of columnar epithelia lining the distal esophagus: (1) a junctional (also called “cardia-type”) epithelium comprised of mucus-secreting cells; (2) a gastric fundic-type epithelium with parietal and chief cells; and (3) intestinal-type metaplasia (also called “specialized columnar epithelium” or “specialized intestinal metaplasia”) with prominent goblet cells. By the early 1980s, it had been established that Barrett’s esophagus was a risk factor for esophageal adenocarcinoma, and intestinal metaplasia was reported to be the esophageal epithelial type most frequently associated with that cancer. By the late 1980s, intestinal metaplasia was widely regarded as both the most common type of Barrett’s epithelium and the one that predisposed to malignancy. In addition, intestinal metaplasia was readily identified histologically by its distinctive goblet cells and, unlike the cardia-type and gastric fundic-type epithelia, intestinal metaplasia clearly was abnormal when found in the region of the gastroesophageal junction. Consequently, some authorities chose to define Barrett’s esophagus by the presence of intestinal metaplasia, and this diagnostic criterion was adopted into clinical practice. Since the 1990s, an esophageal biopsy specimen showing intestinal-type metaplasia with goblet cells has become virtually a sine qua non for the diagnosis of Barrett’s esophagus.

In 1994, Spechler and colleagues reported that 18% of consecutive patients in a general endoscopy unit who had columnar epithelium that involved less than 3 cm of the distal esophagus had intestinal metaplasia. Before then, endoscopists infrequently took biopsy specimens from such short segments of esophageal columnar epithelium. Since then, Barrett’s esophagus has been categorized as long-segment (when the metaplastic epithelium extends ≥3 cm above the gastroesophageal junction) or short-segment (when there is <3 cm of metaplastic epithelium lining the esophagus). The Prague C and M classification, which calls for identifying both the circumferential extent (C) and the maximum extent (M) of Barrett’s metaplasia, is an even more recent system for describing the extent of Barrett’s esophagus endoscopically. Although studies have demonstrated excellent interobserver agreement among endoscopists using the Prague C and M criteria (when columnar epithelium extends >1 cm above the gastroesophageal junction), the clinical benefit of using this system has not been established and, presently, patients with any extent of intestinal metaplasia in the esophagus are managed similarly.

When evaluating studies on Barrett’s esophagus, physicians should consider how changes in diagnostic criteria over the years have impacted the conclusions of those investigations. For example, short-segment Barrett’s esophagus was not widely recognized until 1994, and most studies reported before that year included only patients with long-segment disease. More recent studies, however, include a substantial proportion of short-segment Barrett’s patients whose GERD severity and esophageal cancer risk may differ considerably from those for patients with long-segment disease. It may not be appropriate to extrapolate the results of older studies on the epidemiology and natural history of long-segment Barrett’s esophagus to patients with short-segment disease.

Another recent issue that has caused considerable controversy is whether the diagnosis of Barrett’s esophagus should be limited to patients who have an esophageal biopsy specimen demonstrating intestinal metaplasia (with goblet cells), or whether the finding of gastric cardia-type epithelium in the esophagus also warrants that diagnosis. Cardia-type epithelium traditionally has been considered the normal lining of the proximal stomach (the gastric cardia). However, there are data to suggest that cardia-type epithelium might not be normal, but rather a metaplastic lining that develops as a consequence of GERD. Histochemical and molecular studies of cardia-type epithelium have revealed abnormalities that could predispose to carcinogenesis, and several limited clinical studies support the concept that cardia-type epithelium has malignant potential. Consequently, some authorities have proposed that cardia-type epithelium in the esophagus should be considered Barrett’s esophagus.

Most studies of cancer risk in Barrett’s esophagus have included patients with intestinal metaplasia, either primarily or exclusively. Therefore, the magnitude of the cancer risk associated with cardia-type epithelium in the esophagus is not clear. Pending such clarification, it seems reasonable to limit the diagnosis of Barrett’s esophagus to patients who have intestinal metaplasia. This diagnostic criterion could change in the near future. However, it should be noted that the conceptual definition of Barrett’s esophagus (the condition in which any extent of metaplastic columnar epithelium that predisposes to cancer development replaces the stratified squamous epithelium that normally lines the distal esophagus) does not change, even if specific diagnostic criteria are altered.

Prevalence

Barrett’s esophagus (predominantly the short-segment variety) is found in 10% to 20% of patients who have endoscopic examinations for the evaluation of GERD symptoms. Two relatively recent studies have provided information on the prevalence of Barrett’s esophagus in the general population. In one study from Sweden, 1000 randomly selected adults in the general population had an endoscopic examination performed to look for Barrett’s esophagus. The condition was identified endoscopically and confirmed by an esophageal biopsy specimen showing intestinal metaplasia in 16 individuals (5 long- and 11 short-segment Barrett’s esophagus), representing an overall prevalence of 1.6%. This prevalence rate is likely an underestimate, however, because 60 patients (6%) were found to have intestinal metaplasia in biopsy specimens taken at the gastroesophageal junction, and some of those patients probably had short-segment Barrett’s esophagus that was not recognized by the endoscopists. Interestingly, only 9 (56%) of the 16 individuals identified with Barrett’s esophagus had a history of GERD symptoms (4 [80%] of the 5 with long- and 5 of [46%] of the 11 with short-segment Barrett’s esophagus). In an American study in which 961 patients scheduled for elective colonoscopy agreed to have an upper gastrointestinal endoscopy performed to detect Barrett’s esophagus, the overall prevalence of the condition was 6.8%. Among the 556 patients who had no history of heartburn, short-segment Barrett’s esophagus was found in 5.2%, whereas 5.7% of 384 patients who complained of heartburn had short-segment Barrett’s esophagus.

The aforementioned studies suggest that the prevalence of Barrett’s esophagus in the general adult population is between 2% and 7%. Clearly, Barrett’s esophagus is a very common condition. The studies also suggest that GERD is not a reliable marker for Barrett’s esophagus, especially the short-segment variety. These observations have at least two important implications for clinicians who treat patients with Barrett’s esophagus. First, because the condition is so common, virtually any interventional management strategy applied to the general population of patients with Barrett’s esophagus entails a considerable health care expenditure for society. Second, screening programs for the condition that include only patients with GERD symptoms miss approximately 50% of individuals who have Barrett’s esophagus.

Prevalence

Barrett’s esophagus (predominantly the short-segment variety) is found in 10% to 20% of patients who have endoscopic examinations for the evaluation of GERD symptoms. Two relatively recent studies have provided information on the prevalence of Barrett’s esophagus in the general population. In one study from Sweden, 1000 randomly selected adults in the general population had an endoscopic examination performed to look for Barrett’s esophagus. The condition was identified endoscopically and confirmed by an esophageal biopsy specimen showing intestinal metaplasia in 16 individuals (5 long- and 11 short-segment Barrett’s esophagus), representing an overall prevalence of 1.6%. This prevalence rate is likely an underestimate, however, because 60 patients (6%) were found to have intestinal metaplasia in biopsy specimens taken at the gastroesophageal junction, and some of those patients probably had short-segment Barrett’s esophagus that was not recognized by the endoscopists. Interestingly, only 9 (56%) of the 16 individuals identified with Barrett’s esophagus had a history of GERD symptoms (4 [80%] of the 5 with long- and 5 of [46%] of the 11 with short-segment Barrett’s esophagus). In an American study in which 961 patients scheduled for elective colonoscopy agreed to have an upper gastrointestinal endoscopy performed to detect Barrett’s esophagus, the overall prevalence of the condition was 6.8%. Among the 556 patients who had no history of heartburn, short-segment Barrett’s esophagus was found in 5.2%, whereas 5.7% of 384 patients who complained of heartburn had short-segment Barrett’s esophagus.

The aforementioned studies suggest that the prevalence of Barrett’s esophagus in the general adult population is between 2% and 7%. Clearly, Barrett’s esophagus is a very common condition. The studies also suggest that GERD is not a reliable marker for Barrett’s esophagus, especially the short-segment variety. These observations have at least two important implications for clinicians who treat patients with Barrett’s esophagus. First, because the condition is so common, virtually any interventional management strategy applied to the general population of patients with Barrett’s esophagus entails a considerable health care expenditure for society. Second, screening programs for the condition that include only patients with GERD symptoms miss approximately 50% of individuals who have Barrett’s esophagus.