Acid Reflux and Stromal Fibroblasts in Barrett's Esophagus

Acid Reflux and Stromal Fibroblasts in Barrett's Esophagus

Patients with Barrett's Esophagus are known to have excessive distal esophageal acid exposure comparable to patients with erosive esophagitis. A significant proportion of patients with BE who are not symptomatic on treatment continue to have persistent acid reflux. High dose esomeprazole is able to control acid reflux in patients with BE. The effect of acid reflux on Barrett's esophagus stroma is currently unknown.

It is our hypothesis that stromal fibroblast activation in Barrett's esophagus is influenced by acid reflux. The specific aim of this proposal will be: To assess the association between acid reflux and subepithelial fibroblasts in Barrett's esophagus.

We will conduct a prospective cohort study to assess the degree of stromal activation in patients with LSBE (without dysplasia) who have adequate and inadequate control of acid reflux in the distal esophagus. The study will be conducted in two phases.

Phase 1 (Pilot): 20 patients with LSBE without dysplasia will undergo endoscopy with biopsies and a 24 hour pH study on treatment. Patients will then be divided into 2 groups:

• Group A (GER): Those with ongoing acid reflux (characterized by either presence of esophagitis [LA classification B,C or D1] on endoscopy, and/or a positive pH study on treatment defined using standard criteria)
• Group B (NGER): Those with controlled acid reflux (negative endoscopy and pH study on treatment).

Stromal markers that will be assessed and compared between the 2 groups will include: presence of activated myofibroblasts (detected by immunohistochemistry for vimentin and smooth muscle actin).

Inclusion Criteria:

• Prior histological demonstration of Barrett's esophagus that is endoscopically visible; length of visible segment >/= 1 cms

• Absence of dysplasia on prior biopsies

• Laboratory studies:

  • Prothrombin time (INR) < 1.5
  • Hemoglobin > 8.0 gm/dL

• Ability to provide informed consent

Exclusion Criteria:

• Eastern Cooperative Oncology Group performance status 3 or 4
• Inability to tolerate endoscopic procedures
• Pregnancy: Females of child-bearing age will be screened with pregnancy test. Although none of the procedures in the study are contraindicated in pregnancy, sedation used in endoscopy can be contraindicated in early pregnancy
• Prior esophageal surgery, or cancer