The Relevance of Weakly Acidic Reflux in Patients With Barrett's Esophagus.

We read with great interest the paper by Krishnan et al1 on the factors predicting the persistence of intestinal metaplasia in patients with Barrett’s esophagus before undergoing radiofrequency ablation (RFA). The authors found that uncontrolled, weakly acidic reflux is an important determinant of the incidence of persistent intestinal metaplasia in the distal esophagus, despite twice daily proton pump inhibitor (PPI) therapy before RFA. The advent of 24-hour esophageal pH impedance has allowed us to detect both acid and weakly acidic reflux, although the latter cannot necessarily be identified as a fluid containing bile salts. Moreover, it is well known that PPIs do not reduce the number of reflux episodes, but are only able to change acid into weakly acidic reflux. So, Krishnan et al documented a factor predicting the failure of RFA, but this is mainly the result of an ongoing, powerful, antisecretory therapeutic regimen taken by patients examined in their study instead of a welldefined pathophysiologic phenomenon. Using the same ambulatory pH-impedance technique, we have recently studied a group of patients with Barrett’s esophagus off PPI therapy and showed that they have significantly greater acid and weakly acidic refluxes compared with patients with erosive esophagitis, nonerosive reflux disease, and control subjects. This means that patients with esophageal intestinal metaplasia have an increased reflux not only of acid, but also of weakly acid content independently of the intake of PPI therapy. This combined physiologic abnormality may be responsible for the formation of the esophageal metaplastic epithelium and perhaps for its persistence in those patients who do not benefit from RFA. In other words, also studying Barrett’s patients off PPI therapy would have allowed Krishnan et al to find an uncontrolled weakly acidic reflux as the predictor of RFA failure without the interference of high-dosage PPI treatment, which determines a predominant reflux of this type. Moreover, the results of this study are further confirmation of the fact that weakly acidic reflux is able to induce not only the same symptoms of acid reflux, but is also associated with the same important esophageal histologic lesions, such as intestinal metaplasia, which characterizes patients with Barrett’s esophagus. These findings reinforce the pathogenetic role of weakly acidic reflux in the generation of microscopic esophagitis, and metaplastic esophageal epithelium, and highlight the necessity of controlling this type of reflux to prevent the development of these histologic alterations. Thus, this investigation clearly claims for future studies aimed at testing whether stopping weakly acidic reflux by means of novel drugs or antireflux surgery may contribute to healing mucosal damage in Barrett’s esophagus, or at least preventing RFA failure.