Does suppression of reflux protect against subsequent malignant change?

R.E. Sampliner (Tucson)

Barrett's esophagus is recognized as a premalignant lesion - a metaplastic step that can lead to the development of adenocarcinoma of the esophagus. It is important to separate two processes: metaplasia and neoplasia. Metaplasia - Barrett's esophagus of the specialized type - develops as a result of injury to the squamous lining of the esophagus in the setting of gastroesophageal reflux disease (GERD). Neoplasia occurs on the background of this metaplastic process. Dysplasia and ultimately adenocarcinoma of the esophagus develop as a result of cell cycle abnormalities and genomic instability. It would be reasonable to assume that control of GERD may prevent the development or the progression of the metaplastic process. However, there is no reason to expect that control of reflux will effect the neoplastic process. If profound acid suppression results in complete regression of Barrett's esophagus - which has not been proven to date - then one could assume that neoplasia would not develop.

In the preproton pump inhibitor era, pharmacologic therapy has not had an impressive impact in Barrett's esophagus [1,2]. It is too early to draw a conclusion on the impact of proton pump inhibition. Although there are favorable early reports [3,4], there are other trials that have failed to show a systematic response over a period of 1-2 years of therapy [5,6].

The surgical experience may provide the best evidence that suppression of reflux will fail to protect against subsequent malignant change. In perhaps the best documented case, the patient underwent subtotal resection of Barrett's esophagus with a colonic interposition. Prolonged pH probe recording failed to show abnormal acid exposure yet the patient developed adenocarcinoma in the remnant of Barrett's esophagus [7]. Many other cases of adenocarcinoma of the esophagus after antireflux surgery are scattered in the surgical literature with lesser documentation of ablation of esophageal acid exposure [8-10].

Suppression of reflux has not been proven to protect against malignant change and may not be expected to on a theoretical basis.

References

1. Sampliner RE, Garewal HS, Fennerty MB et al. Lack of impact of therapy on extent of Barrett's esophagus in 67 patients. Dig Dis Sci 1990;35:93-96.

2. Cameron AJ, Lomboy CT Barrett's esophagus: age, prevalence, and extent of columnar epithelium. Gastroenterology 1992;103:1241-1245.

3. Devière J, Buset M, Dumonceau J-M et al. Regression of Barrett's epithelium with omeprazole. N Engl J Med 1989;320: 1497-1498.

4. Gore S, Healey CJ, Sutton R et al. Regression of columnar lined (Barrett's) esophagus with continuous omeprazole therapy. Gastroenterology 1992;102:A75.

5. Sampliner RE, Mackel C, Jennings D et al Effect of 12 months of a proton pump inhibitor (lansoprazole) on Barrett's esophagus - a randomized trial Gastroenterology 1992; 102:A157.

6. Bologna S, Blumenkehl M, Schubert TT et al. Barrett's esophagus response to long-term omeprazole therapy. Gastrointest Endosc 1992;38:A229.

7. Hamilton SR, Hutcheon DF, Ravitch WJ et al. Adenocarcinoma in Barrett's esophagus after elimination of gastroesophageal reflux. Gastroenterology 1984;86:356-360.

8. Haggitt RC, Tryzelaar J, Ellis FH et al Adenocarcinoma complicating columnar epithelium-lined (Barrett's) esophagus. Am J Clin Pathol 1978;70:l-5.

9. Cameron AJ, Ott BJ, Payne WS. The incidence of adenocarcinoma in columnar lined (Barrett's) esophagus N Engl J Med 1985:311:857-859.

10. Williamson WA, Ellis FH, Gibb SP. Effect of antireflux operation on Barrett's mucosa. Ann Thorac Surg 1990;49:537-542.