Role of Acid Suppression in the Development and Progression of Dysplasia in Patients with Barrett’s Esophagus

Abstract

Barrett’s esophagus (BE) usually develops in patients with gastroesophageal reflux disease and therefore it has been suggested that esophageal acid exposure plays an import role in the initiation of BE and its progression towards esophageal adenocarcinoma (EAC). The mechanisms whereby acid exposure causes BE are not completely revealed and the potential role of esophageal acid exposure in carcinogenesis is unclear as well. Since acid exposure is thought to play an important role in the progression of BE, therapies aimed at preventing the development of EAC have primarily focused on pharmacological and surgical acid suppression. In clinical practice, acid suppression is effective in relieving reflux symptoms and decreases esophageal acid exposure in most patients. However, in some individuals, pathological acid exposure persists and these patients continue to be at risk for developing dysplasia or EAC. To date, published trials suggest that acid suppression is able to prevent the development and progression of dysplasia in patients with BE, but definite and compelling proof is still lacking. This article reviews the mechanisms of acid-induced carcinogenesis in BE and the role of acid suppression in the prevention of neoplastic progression.

Impact of surveillance for Barrett's oesophagus on tumour stage and survival of patients with neoplastic progression

“…Although it is difficult to compare survival of both groups due to different types of bias, including lead time bias and length time bias, this large difference seems clinically relevant. The results correspond to those of previous retrospective and small prospective studies, which report an overall 5-year survival of 65–100% in patients with OAC during surveillance and 0–30% in patients with symptomatic OAC 6 10 14 16 17 20 24 37 38. The majority of patients undergoing BO surveillance died due to cardiovascular diseases or malignancies and only 4% due to OAC, which was comparable to cause of death in individuals with similar age and gender in the general population.…”

“…The development of OAC in BO is a gradual process, in which metaplastic epithelium without dysplasia evolves to low-grade dysplasia (LGD), high-grade dysplasia (HGD) and eventually OAC under the influence of oesophageal acid exposure 5 6. Once a patient has developed OAC the prognosis is poor with a 5-year survival of less than 20% 7–9.…”

Proton Pump Inhibitors Do Not Reduce the Risk of Esophageal Adenocarcinoma in Patients with Barrett’s Esophagus: A Systematic Review and Meta-Analysis

“…Approximately 10% of patients with several longstanding chronic gastroesophageal reflux disease (GERD) will eventually develop BE as a complication of GERD [2]. In the general population, the prevalence of BE is estimated at 1–2%, with white males over 60 years of age predominantly affected [3]. As BE is the single most important risk factor for the development of esophageal adenocarcinoma (EAC), and since the incidence of EAC has increased exponentially over the past 3 decades, increased attention has been focused on preventing the progression from BE to EAC or its immediate precursor lesion, high-grade dysplasia (HGD) [4–7].…”

Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus

“…Patients with BO have an increased risk of developing OAC with an estimated incidence of 0.5% per year 3 4. The development of OAC is thought to be a gradual process, in which metaplastic epithelium evolves to low-grade dysplasia (LGD), high-grade dysplasia (HGD) and eventually OAC under the influence of chronic oesophageal acid exposure 5 6. Early identification of a premalignant stage provides the opportunity to prevent progression to BO-related adenocarcinoma and endoscopic surveillance is therefore recommended for patients with BO 7.…”