Application of confocal laser endomicroscopy in the diagnosis and management of Barrett’s esophagus

Since its description in the 1950s, the definition of Barrett's esophagus has evolved from the macroscopic visualization of gastric-appearing mucosa in the esophagus to the histologic identification of goblet cells confirming the presence of intestinal metaplasia within the esophagus. The length of intestinal metaplasia necessary to be classified as Barrett's, and the relationship between intestinal metaplasia of the esophagus and that limited to the cardia are all areas currently being evaluated. However, any segment of intestinal metaplasia is capable of undergoing dysplastic change and ultimately of becoming a focus of adenocarcinoma. It is logical to expect the degree of risk for developing cancer to be proportional to the amount of intestinal metaplasia present; however, within a population, the low risk to any individual is balanced by the relative frequency of the process. Thus, given the large numbers of people in America with CIM, even a small risk of progression to cancer will result in a large number of patients with adenocarcinoma of the cardia. This is exactly what is occurring today, with the incidence of adenocarcinoma of the cardia and esophagus currently rising faster than any other cancer in the United States. A major risk factor for adenocarcinoma of the esophagus is intestinal metaplasia, which occurs as a consequence of GERD. Patients with Barrett's esophagus usually have more severe reflux disease with significant impairment of LES function and esophageal body motility compared with patients without Barrett's. Furthermore, in patients with Barrett's, the composition of the refluxed juice is different. Patients who reflux both gastric and duodenal juice have a higher prevalence of Barrett's than do those who reflux gastric juice alone. Among patients with Barrett's, a significantly greater esophageal bilirubin exposure has been demonstrated in those with dysplasia. The mechanically defective sphincter and impaired esophageal body function in many patients with Barrett's makes their disease difficult to control medically. In addition, symptoms are unreliable as a guide to successful control of reflux. The hardest symptom to control is regurgitation, and there is concern that this and continued reflux of pharmacologically altered gastric contents, particularly bile acids in their nonpolar form, may contribute to progression of Barrett's. Both medical therapy and failed antireflux surgery are associated with progression of Barrett's to dysplasia and adenocarcinoma. On the other hand, a functioning fundoplication seems to be associated with protection from progression of Barrett's. Intestinal metaplasia of the esophagus is unlikely to regress after antireflux surgery; however, intestinal metaplasia limited to the cardia is perhaps more dynamic and able to regress. Furthermore, low-grade dysplasia frequently regresses after an antireflux procedure. Antireflux surgery is safe, effective, and durable, and often can be performed using minimally invasive techniques. Thus, antireflux surgery should be strongly considered in any patient with intestinal metaplasia of the esophagus or cardia. The possibility of mucosal ablation after an antireflux repair should be considered in patients with low-grade dysplasia. Patients with Barrett's and high-grade dysplasia are at high risk for having a focus of adenocarcinoma present. Even with multiple biopsies, a degree of sampling error exists. Also, adenocarcinoma can develop within the space of several months; and if the cancer is allowed to invade into the submucosa, 50% of these patients will have lymphatic metastases, thereby negating the purpose of surveillance. Although patients with high-grade dysplasia and intramucosal adenocarcinoma on biopsy who do not have an endoscopically visible lesion are unlikely to have lymphatic metastases, 7% do have submucosal invasion. Thus, even in these very early tumors, treatment directed only at the mucosa may be inadequate. (ABSTRACT