Barrett's Esophagus: Emerging Knowledge and Management Strategies

Abstract

The incidence of esophageal adenocarcinoma (EAC) has increased exponentially in the last 3 decades. Barrett's esophagus (BE) is the only known precursor of EAC. Patients with BE have a greater than 40 folds higher risk of EAC compared with the general population. Recent years have witnessed a revolution in the clinical and molecular research related to BE. However, several aspects of this condition remain controversial. Data regarding the true prevalence of BE have varied widely. Recent studies have suggested a lower incidence of EAC in nondysplastic BE (NDBE) than previously reported. There is paucity of prospective data showing a survival benefit of screening or surveillance for BE. Furthermore, the ever-increasing emphasis on healthcare cost containment has called for reexamination of the screening and surveillance strategies for BE. There is a need for identification of reliable clinical predictors or molecular biomarkers to risk-stratify patients who might benefit the most from screening or surveillance for BE. Finally, new therapies have emerged for the management of dysplastic BE. In this paper, we highlight the key areas of controversy and uncertainty surrounding BE. The paper discusses, in detail, the current literature about the molecular pathogenesis, biomarkers, histopathological diagnosis, and management strategies for BE.

Figure 1

(a) Schematic representation of the Prague criteria for endoscopically suspected esophageal columnar metaplasia/Barrett's esophagus, Step 1: recognize the presence of hiatal hernia; Step 2: identify GEJ and record depth of scope insertion; Step 3: recognize suspected BE mucosa above the GEJ; Step 4: record the depth of scope insertion at the most proximal circumferential extent of BE; Step 5: record the depth of scope insertion at maximum extent of BE; Step 6: subtract the depth of insertion for circumferential and maximum extents from the depth of scope insertion at the GEJ to calculate C and M, respectively. *Endoscopically suspected columnar mucosa. Adapted from [16]. (b) endoscopic image of Barrett's esophagus for circumferential (C) and maximum (M) extent of columnar mucosa, corresponding to the schematic representation shown in Figure 1(a), (c) another endoscopic image of BE using narrow-band imaging (NBI). NBI is a high-resolution endoscopic tool that enhances mucosal surface details without the need for special dyes (electronic chromoendoscopy).

Figure 2

(a) Intestinal metaplasia is defined by the presence of goblet cells distended with mucin. In this photomicrograph there is no dysplasia, as evidenced by presence of surface maturation. Surface epithelial cells show uniform mucin caps and well-polarized nuclei. (b) Low-grade dysplasia of the intestinal type is characterized by hyperchromatic elongate nuclei that are seen in both the crypts and the surface epithelium (i.e., loss of surface maturation). (c) Presence of glandular crowding, nuclear stratification, and loss of nuclear polarity signifies high-grade dysplasia. (d) Glandular complexity, budding, and presence of incomplete glandular profiles are evidence of lamina propria invasion (intramucosal carcinoma).