PPI's are Associated With Reduced Incidence of Dysplasia in BE
Background and Aims: Esophageal acid exposure is important in the pathogenesis of Barrett's esophagus (BE), and possibly in the progression of BE to dysplasia and carcinoma. The aim of this study is to compare the development of dysplasia in BE patients treated with or without proton pump inhibitor (PPI) or histamine 2-receptor antagonist (H2RA).
Methods: We analyzed prospectively collected data by a single endoscopist on patients with BE in a VA (Veterans Affairs) setting over a 20-yr time period (1981-2000). A pathologist used standard criteria to diagnose BE/dysplasia. Pharmacy information after 1994 was retrieved from a computerized database, and from research files for the period before that. The receipt and the duration of H2RA and/or PPI use was compared between those with and without dysplasia. The incidence of dysplasia was examined in a Kaplan-Meier survival analysis stratified by PPI treatment status, and the risk of dysplasia was examined in a Cox multiple regression analysis controlling for demographic features, length of BE, and the year of BE diagnosis.
Results: We analyzed data for 236 unique veteran patients with a mean age at BE diagnosis of 61.5 yr, 86% Caucasian, and 98% male. During 1,170 patient-yr of follow-up, 56 patients developed dysplasia giving an annual incidence rate of 4.7%. Of those, 14 had high-grade dysplasia. The cumulative incidence of dysplasia was significantly lower among patients who received PPI after BE diagnosis than in those who received no therapy or H2RA; log rank test (p< 0.001). Furthermore, among those on PPIs, a longer duration of use was associated with less frequent occurrence of dysplasia. In multivariate analysis, the use of PPI after BE diagnosis was independently associated with reduced risk of dysplasia, hazards ratio: 0.25 (95% CI 0.13-0.47), p< 0.0001. Longer segments of BE and Caucasian race were other independent risk factors for developing dysplasia. In general, similar findings were observed when only cases with high-grade dysplasia were analyzed.
Conclusions: These results indicate that PPI therapy is associated with a significant reduction in the risk of developing dysplasia in patients with BE. However, more studies are required to confirm this finding.

The change from normal esophageal squamous epithelium to columnar epithelium with goblet cells is termed Barrett's esophagus (BE). BE is thought to represent an epithelial response to chronic exposure to acid reflux. BE is the single most significant risk factor for esophageal adenocarcinoma. In a small number of patients with BE, metaplasia will progress to dysplasia and in even fewer from dysplasia to adenocarcinoma. Recent clinical and basic science data suggest that acid reflux may play a key role in the development of esophageal cancer. However, the role that acid suppression may have on malignant progression is unclear.

There is epidemiological evidence that acid exposure increases the likelihood of adenocarcinoma. Lagergren et al., in a population-based case-control study, found a strong association between reflux symptoms and esophageal adenocarcinoma. Once esophageal metaplastic change occurs, progression to dysplasia/adenocarcinoma is observed in patients with more significant acid exposure. Avidan et al., in a retrospective study, observed that patients with high-grade dysplasia and/or adenocarcinoma had more frequent episodes of acid reflux and longer acid contact time in the esophagus than patients with BE alone and patients with erosive esophagitis.

The use of profound acid suppression such as that produced by proton pump inhibitor (PPI) has the potential of modifying the clinical course of gastroesophageal reflux disease (GERD). For example, acid suppression has been shown to effectively prevent the recurrence of erosive esophagitis and/or esophageal strictures. Our anecdotal observations also indicate that the incidence of esophageal peptic strictures is declining in recent times.

Whether acid suppression could alter the natural history of metaplasia remains unknown. Many studies have been published on the impact of acid suppression on the length of BE demonstrating little overall change. Even anti-reflux surgical therapy has had little impact on the length of BE. The role of acid suppression in conjunction with endoscopic ablation of BE has also been evaluated with unclear results. Few studies have examined the effects of acid suppression on progression of BE to cancer. Clinical evidence suggesting that acid suppression could alter the metaplasia-dysplasia-adenocarcinoma progression has been lacking. Both medical and surgical means of suppressing acid have failed to alter the incidence of esophageal dysplasia/adenocarcinoma in a consistent manner. The aim of this study is to compare the development of dysplasia in a cohort of patients with BE who received acid suppressive therapy versus those patients who did not receive therapy.