Chemoprevention of Barrett’s Esophagus and Esophageal Adenocarcinoma

Barrett’s esophagus is common in Western countries, but progression to esophageal adenocarcinoma is uncommon. Chemoprevention therefore needs to consider whether benefits outweigh risks given an otherwise healthy population. This will depend on the particular population at risk and the relative safety of a potential preventive agent. Most evidence regarding the potential benefit of chemoprevention of Barrett’s esophagus and prevention of progression to esophageal adenocarcinoma is based on observational studies such as case–control and cohort studies. Given the potential benefits and relatively low risks, patients with BE should receive once-daily PPI therapy, but routine use of twice-daily PPI is not recommended unless necessitated by poor control of reflux symptoms or esophagitis. Recent data suggest that the inverse associations between aspirin/NSAID use and esophageal adenocarcinoma may be the result of reducing neoplastic progression (from metaplasia to dysplasia and carcinoma) rather than initiation of Barrett’s esophagus. While substantial associative data suggest a potential benefit of aspirin and nonaspirin NSAIDs in reducing the risk of progression of Barrett’s esophagus, the low risk of progression and the potential risks (gastrointestinal bleeding, complicated ulcer disease, hemorrhagic stroke) do not warrant routine use, unless dictated by cardiovascular risk. Chemoprevention after mucosal ablation in those at highest risk of post-ablation recurrence (dysplastic Barrett’s) is currently under investigation.     

Natural History of Barrett’s Esophagus

Barrett’s esophagus (BE) is a very common condition. We have obtained fairly profound knowledge of the natural history of this condition. This results from many cross-sectional and cohort studies, many describing patients undergoing long-term surveillance. Their consent to use their clinical data has improved our knowledge to the benefit of these same and other patients. The prevalence of BE increases with age both in men and in women. This increase starts at a younger age in men than in women. The incidence of high-grade dysplasia and cancer in BE depends on segment length, gender, and age. The latter two likely indicate the duration of the presence of BE in an individual patient. Other factors that influence the incidence of dysplasia and cancer are smoking behavior and use of certain medications such as PPIs, statins, and NSAIDs. Surveillance of BE and treatment of dysplasia can impact the incidence of and mortality due to esophageal adenocarcinoma. This is of major benefit to a subgroup of BE patients. The epidemiology and burden of disease ask for further efforts to develop targeted screening, surveillance, and intervention techniques in coming years.     

Celiac Disease and Intestinal Metaplasia of the Esophagus (Barrett’s Esophagus)

Previous studies on celiac patients demonstrated that exposure to gliadin alters the motility of the upper gastrointestinal tract, leading to increased acid reflux. No literature is available regarding the possible presence of specialized intestinal metaplasia of the esophagus as a consequence of chronic reflux in adult celiac patients. Our purpose was to evaluate endoscopically and histologically the esophagi of a group of untreated celiac patients. We studied 60 celiac patients, 13 men and 47 women (mean age, 40 ± 14 [SD] years; range, 18–80 years), at their first endoscopy (following a normal diet). The distal esophagus was evaluated and multiple biopsies were taken. Hematoxylin–eosin and alcian blue stainings were performed. A group of nonceliac, age- and sex-matched patients was used as a control. We found intestinal metaplasia in the distal esophagus of 16 of 60 (26.6%) celiacs (mean age, 45 ± 13 years; range, 27–75 years), in comparison with a control-group prevalence of 10.9% (OR, 3.9; 95% CI, 1.4–11.2%). Among the celiac group with metaplasia, only one patient had reflux-like symptoms. None had esophagitis. In conclusion, we observed an increased prevalence of esophageal metaplasia in patients with celiac disease. This finding could be the result of motor abnormalities leading to chronic acid reflux, combined with a mucosa which is sensitive to gliadin.     

Cellular Origins of Barrett’s Esophagus: the Search Continues

Purpose of Review

The cellular origins of Barrett’s esophagus remain elusive. In this review, we discuss the potential cellular mechanisms behind squamous to columnar metaplasia as well as the limitations of these proposed mechanisms.

Recent Findings

Several theories have been proposed, including the reprogramming of native squamous cells, repopulation from submucosal glands, contributions from circulating bone marrow-derived cells, and direct extension of gastric cells. Most recent data support an innate progenitor cell unique to the squamocolumnar junction that can expand into metaplastic glands.

Summary

Active investigation to clarify each of these potential cells of origin is being pursued, but ultimately each could contribute to the pathogenesis of Barrett’s esophagus depending on the clinical context. Nonetheless, identifying cells of origin is critical to understand the molecular mechanisms behind Barrett’s esophagus and developing strategies to better treat (and possibly prevent) this increasingly significant premalignant disease.