Barrett metaplasia

**Definition:** Metaplastic change of the distal esophageal lining from non-keratinized stratified squamous epithelium to intestinal-type columnar epithelium with goblet cells (intestinal metaplasia). Endoscopically, it appears as salmon-pink, velvety mucosa extending proximally from the gastroesophageal junction. Biopsy confirmation of goblet cells is required in the US (ACG criteria). Some other guidelines (e.g., British Society of Gastroenterology) accept columnar metaplasia without goblet cells.

**Pathophysiology:** - Chronic gastroesophageal reflux (acid and bile) injures squamous mucosa. The repair process leads to metaplasia, which is an adaptive change to a more acid-resistant epithelium. - Metaplasia is a reversible change in cell type, driven by altered transcription factors (e.g., CDX2 upregulation) in stem/progenitor cells. - Progression: metaplasia → low-grade dysplasia → high-grade dysplasia → adenocarcinoma. Molecular changes include TP53 loss/mutation, CDKN2A (p16) inactivation, and aneuploidy.

**Risk factors:** Long-standing GERD (>5 years), male sex, age >50, White race, obesity (especially central/visceral adiposity), tobacco use, hiatal hernia, and family history. Alcohol is not a clear independent risk factor.

**Clinical features:** - Often asymptomatic or has typical GERD symptoms: heartburn, regurgitation, and dysphagia. - New dysphagia or odynophagia, weight loss, or GI bleeding suggests a stricture or adenocarcinoma.

**Diagnosis:** Upper endoscopy with biopsies (Seattle protocol: 4-quadrant biopsies every 1–2 cm). Histology shows columnar epithelium with goblet cells (intestinal metaplasia).

**Complications:** - Esophageal **adenocarcinoma** (the key association). Risk is about 0.2–0.5% per year in non-dysplastic Barrett. - Esophageal strictures and ulcers.

**Management:** - Acid suppression with a PPI. - Surveillance endoscopy: every 3–5 years for non-dysplastic Barrett, more often with dysplasia. - Low-grade dysplasia: endoscopic eradication therapy (radiofrequency ablation) or close surveillance. - High-grade dysplasia or intramucosal cancer: endoscopic mucosal resection plus radiofrequency ablation. - Esophagectomy is reserved for invasive disease beyond what endoscopic therapy can treat. - Antireflux surgery (Nissen fundoplication) is an option for refractory GERD but does not eliminate cancer risk.

**High-yield board points:** - Barrett esophagus is the classic example of **metaplasia**. It is not dysplasia and not cancer. - Squamous → columnar change is the most common board-tested example. - Barrett → **adenocarcinoma** (distal third of the esophagus). Squamous cell carcinoma is associated with alcohol and tobacco and occurs in the upper/middle third. Adenocarcinoma in the US now outnumbers SCC. - Barrett is a complication of GERD, as are esophagitis and strictures. - Metaplasia is potentially reversible if the stimulus is removed, but Barrett typically persists despite PPI therapy.

**Mnemonic:** The esophagus "switches uniforms" from squamous to columnar (gut-like) to withstand acid. This is adaptive but cancer-prone.