Columnar mucosa and intestinal metaplasia of the esophagus: fifty years of controversy

Abstract

Objective: To outline current concepts regarding etiology, diagnosis, and treatment of intestinal metaplasia of the esophagus and cardia.

Summary background data: Previously, endoscopic visualization of columnar mucosa extending a minimum of 3 cm into the esophagus was sufficient for the diagnosis of Barrett's esophagus, but subsequently the importance of intestinal metaplasia and the premalignant nature of Barrett's have been recognized. It is now apparent that shorter lengths of intestinal metaplasia are common, and share many features of traditional 3-cm Barrett's esophagus.

Methods: Themes and concepts pertaining to intestinal metaplasia of the esophagus and cardia are developed based on a review of the literature published between 1950 and 1999.

Results: Cardiac mucosa is the precursor of intestinal metaplasia of the esophagus. Both develop as a consequence of gastroesophageal reflux. Intestinal metaplasia, even a short length, is premalignant, and the presence of dysplasia indicates progression on the pathway to adenocarcinoma. Antireflux surgery, as opposed to medical therapy, may induce regression or halt progression of intestinal metaplasia. The presence of high-grade dysplasia is frequently associated with an unrecognized focus of adenocarcinoma. Vagal-sparing esophagectomy removes the diseased esophagus and is curative in patients with high-grade dysplasia. Invasion beyond the mucosa is associated with a high likelihood of lymph node metastases and requires lymphadenectomy.

Conclusions: Despite improved understanding of this disease, controversy about the definition and best treatment of Barrett's esophagus continues, but new molecular insights, coupled with careful patient follow-up, should further enhance knowledge of this disease.

Figure 1. Acid and bilirubin exposure times for patients with Barrett’s esophagus with and without complications. The presence of a stricture, ulcer, low-grade dysplasia, or high-grade dysplasia was considered a complication. The median is indicated by a line, the interquartile range by a box.

Figure 2. Dissociation curve for bile acids demonstrating the critical pH range from 3 to 6 where bile acids exist in their soluble, unionized form and can penetrate cell membranes, accumulate within mucosal cells, and become toxic to the mitochondria. At pH 2, bile acids irreversibly precipitate from solution, whereas at pH 7, bile acids exist in their noninjurious ionized form.

Figure 3. Hayward’s depiction of the gastroesophageal junction and region of the cardia. Line X-Y crosses the esophagogastric junction. Everything above the line is esophagus, and everything below is stomach. From A to C is esophagus lined by squamous epithelium. The phrenoesophageal ligament inserts at B. From B to D is the area of the esophagus called the cardia. It is partially lined by squamous epithelium (from B to C) and partially lined by cardiac mucosa (from C to D). Cardiac mucosa joins with fundic gastric mucosa at point E, whereas pure fundic mucosa is present at point F. (From Hayward J. The lower end of the esophagus. Thorax 1961; 16:36–41. Reproduced with permission from the BMJ Publishing Group.)

Figure 4. Correlation between acid exposure as determined by 24-hour pH monitoring and the length of cardiac-type columnar epithelium without intestinal metaplasia in the esophagus. The length of cardiac mucosa was measured from the endoscopic gastroesophageal junction to the site of the highest biopsy showing cardiac-type columnar epithelium on histologic examination.

Figure 5. The prevalence of intestinal metaplasia in cardiac-type mucosa of varying extents: limited to the gastroesophageal (GE) junction and involving short (<3 cm) and long (≥3 cm) segments of the esophageal body. (Reproduced with permission from Oberg S, DeMeester TR, Peters JH, et al. The extent of Barrett’s esophagus depends on the status of the lower esophageal sphincter and the degree of esophageal acid exposure. J Thorac Cardiovasc Surg 1999; 117:572–580.)

Figure 6. Review of the English language literature identified 11 series in which patients with Barrett’s were followed up after antireflux surgery. A total of 340 patients were followed up for an overall mean of 4.4 years (range 1–18 years). Most patients (74%) did not have any change in their Barrett’s with follow-up. Regression occurred in 17% of patients, progression in 9%.

Figure 7. Review of the English language literature identified 11 series in which patients with Barrett’s were followed up after antireflux surgery. In 4 of the 11 series, adenocarcinoma developed in no patients during the follow-up period. A total of 346 patients were followed up and 12 cancers occurred. Seven additional cases of adenocarcinoma developing in Barrett’s esophagus after an antireflux procedure were found in other reports. Thus, a total of 19 adenocarcinomas that occurred after an antireflux procedure were found in the literature. Each case of cancer is plotted on the time line at the point where it occurred. Time is marked in 5-year segments, with 0 the time of the antireflux procedure. Note the maximum as well as the mean or median follow-up for each of the 11 series. Despite the long follow-up in these series, most cancers are clustered between 0 and 5 years after the antireflux procedure. These cancers probably occurred as a consequence of cellular and genetic alterations that took place before the fundoplication. For each of the cancers occurring after 5 years, there was evidence either by the recurrence of reflux symptoms or a positive 24-hour pH test that the fundoplication had failed.