Epidemiology and Etiology
Epidemiology
- Incidence: approximately 1%–10% in the United States
- Mean age is approximately 55 years.
- Men are more commonly affected.
- More prevalent in whites
Etiology
- Gastroesophageal reflux disease (GERD)
- Erosive esophagitis
- Peptic stricture
- Hiatal hernia
- Smoking: has a synergistic effect with GERD
- Central obesity
- Family history
- Oral bisphosphonates
Pathophysiology
Mucosal injury
- Chronic reflux of gastric acid
- pH
- Duration of exposure
- Compromised protection mechanisms
- Antireflux barrier
- Lower esophageal sphincter (LES)
- Extrinsic compression of the diaphragm
- Clearing mechanism
- Gravity
- Bicarbonate secretion from esophageal and salivary glands
- Peristalsis
- Epithelial defense factors to resist acid entry into intercellular spaces
- Thick epithelial layer
- Tight junctions
- Lipid-rich intercellular space
- Antireflux barrier
Metaplasia
- Occurs when 1 type of differentiated tissue replaces another
- Adaptive response to injury
- Mechanism:
- Erosion of mucosa → inflammatory cell infiltration → epithelial necrosis
- Repair of damaged esophagus → replacement with columnar cells
- Transdifferentiation of squamous epithelium into columnar epithelium
- Potential migration of progenitor or residual embryonic from gastric cardia or gastroesophageal junction
Dysplasia
- Acid and bile salts → oxidative DNA damage in epithelial cells → cell proliferation and abnormal development
- Likely also a genetic component
- Patients are at risk for esophageal adenocarcinoma.
Barrett’s esophagus metaplasia.
Schematic demonstrating the development of metaplasia after injury to the esophageal epithelium in Barrett’s esophagus. There are several proposed mechanisms.
A: Repair of reflux-induced injury leads to transdifferentiation of esophageal epithelial cells.
B: Repair of damaged tissue results from progenitor cells of the gastric cardia.
C: Repair of damaged tissue results from residual embryonic cell migration from the gastroesophageal junction or gastric cardia.
Clinical Presentation and Diagnosis
Clinical presentation
- Patients present with symptoms associated with GERD and its complications.
- Heartburn
- Regurgitation
- Dysphagia
- Odynophagia
- Physical exam is generally unremarkable.
Diagnosis
Screening:
- Recommended in high-risk patients with GERD
- Long-standing symptoms (> 5 years)
- Age > 50 years
- Smoking history
- Obesity
- First-degree relative with esophageal adenocarcinoma
- Screening of the general public is not recommended.
Esophagogastroduodenoscopy (EGD):
- Procedure of choice
- Gross findings:
- Evidence of columnar epithelium
- Erythematous distal esophagus
- Velvet or “tongue”-like texture
- Squamous epithelium is usually pale and glossy.
- Squamocolumnar junction (Z-line, where columnar and squamous epithelium meet in the esophagus)
- ≥ 1 cm above the gastroesophageal junction (GEJ)
- Irregular border
- Evidence of columnar epithelium
- Biopsy findings:
- Required for diagnosis
- Columnar epithelium
- Goblet cells (mucin-secreting cells, seen in the intestinal mucosa)
- Gastric foveolar-type cells (mucin-secreting glands, normally seen in the gastric mucosa)
Esophagogastroduodenoscopy revealing erythematous epithelium in the distal esophagus, consistent with Barrett’s esophagus. Notice the difference between the erythema of the columnar epithelium and the pale, glossy squamous epithelium. This junction is known as the Z-line.
Image: “Esophageal granular cell tumor colliding with intramucosal adenocarcinoma” by Alkhoury F, Martin JT, Fiedler P, Jaffe PE. License: CC BY 3.0
Esophageal mucosal biopsy showing columnar epithelium and numerous goblet cells (light-blue cells in front of the white arrow), consistent with Barrett’s esophagus.
Image: “Barrett’s mucosa” by The Armed Forces Institute of Pathology (AFIP). License: Public Domain
Management and Complications
Management
Management goal is to treat underlying acid reflux to decrease the risk of cancer development.
- Proton pump inhibitors (PPIs)
- Preferred over H2-receptor blockers
- Treatment is indefinite.
- Common choices:
- Omeprazole
- Pantoprazole
- Diet modifications, aiming to avoid:
- Fatty foods
- Acidic foods and drinks
- Caffeine
- Alcohol
- Eating prior to bedtime
- Avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs)
- Weight loss
Surveillance and dysplasia management
- The intention is to detect dysplasia and adenocarcinoma early so that treatment can be initiated promptly.
- Involves repeated EGD and biopsy sampling:
| Endoscopy biopsy findings | Management |
|---|---|
| Barrett’s esophagus (metaplasia only) | PPIs and EGD every 2–3 years |
| Low-grade dysplasia | PPIs and EGD every 6–12 months |
| High-grade dysplasia | Endoscopic ablation or resection (endoscopic or surgical) |
Hematoxylin and eosin staining of esophageal mucosal biopsies.
A: non-dysplastic Barrett’s mucosa characterized by uniform, bland nuclei arranged in a surface monolayer
B: low-grade dysplasia exhibiting nuclear hyperchromasia, elongation, and stratification extending up to the surface epithelium
C: high-grade dysplasia depicting increased architectural and cytologic complexity, including loss of nuclear polarity
D: intramucosal adenocarcinoma characterized by severe architectural distortion, including angulated glands. (a–d, 100×)
Complications
Esophageal adenocarcinoma is the most significant morbidity.
- Uncommon overall
- Helicobacter pylori infection is actually protective.
- Requires referral to oncology
- Management depends on staging and the patient’s overall health.
Differential Diagnosis
- Esophageal adenocarcinoma: a malignant tumor of the distal esophagus. Barrett’s esophagus, obesity, and smoking are risk factors for this malignancy. Patients may present with dysphagia, regurgitation, and weight loss. Esophagogastroduodenoscopy and biopsy will help diagnose and differentiate this from Barrett’s esophagus. Management is based on staging and the overall health of the patient but may include surgical resection, radiation, and chemotherapy.
- Esophageal squamous cell carcinoma: a malignant tumor of the middle esophagus. Risk factors include smoking and alcohol. Symptoms are similar to esophageal adenocarcinoma and include dysphagia, regurgitation, and weight loss. Esophagogastroduodenoscopy and biopsy will establish the diagnosis and differentiate it from Barrett’s esophagus. Treatment depends on staging and the patient’s overall health but includes surgical resection, radiation, and chemotherapy.
- Eosinophilic esophagitis: a chronic, immune-mediated condition of the esophagus, which leads to esophageal dysfunction. Symptoms include heartburn, chest pain, dysphagia, and food impaction. Esophagogastroduodenoscopy and biopsy will show strictures, stacked circular rings, linear furrows, and eosinophil-predominant inflammation, differentiating this condition from Barrett’s esophagus. Management includes an evaluation of food allergies, PPIs, and topical glucocorticoids.
- Gastroesophageal reflux disease (GERD): a condition caused by reflux of gastric contents into the esophagus, which can lead to irritation and erosion. Gastroesophageal reflux disease is a precursor to Barrett’s esophagus. Symptoms include heartburn, dysphagia, chest pain, and nausea. Diagnosis is usually clinical, but those with severe symptoms or risk factors may require EGD. This can help differentiate it from Barrett’s esophagus. Treatment includes lifestyle modifications and PPIs.
References
- Spechler, S.J. (2020). Barrett’s esophagus: Epidemiology, clinical manifestations, and diagnosis. UpToDate. Retrieved November 2, 2020, from https://www.uptodate.com/contents/barretts-esophagus-epidemiology-clinical-manifestations-and-diagnosis
- Spechler, S.J. (2020). Barrett’s esophagus: Pathogenesis and malignant transformation. UpToDate. Retrieved November 2, 2020, from https://www.uptodate.com/contents/barretts-esophagus-pathogenesis-and-malignant-transformation
- Spechler, S.J. (2020). Barrett’s esophagus: Surveillance and management. UpToDate. Retrieved November 2, 2020, from https://www.uptodate.com/contents/barretts-esophagus-surveillance-and-management
- Johnston, M.H., and Eastone, J.A. (2017). Barrett esophagus. In Roy, P.K. (Ed.), Medscape. https://emedicine.medscape.com/article/171002-overview
