Barrett’s Esophagus

Barrett’s esophagus is a chronic gastroesophageal reflux disease (GERD) that leads to the replacement of stratified squamous epithelium with gastric columnar epithelium in the esophagus. The condition is associated with an increased risk of esophageal adenocarcinoma. Workup includes an esophagogastroduodenoscopy (EGD) showing proximal displacement of the squamocolumnar junction (Z-line) from the gastroesophageal junction (GEJ). Biopsies will confirm the diagnosis by revealing columnar epithelium and goblet cells in the distal esophagus. Treatment is primarily with proton pump inhibitors (PPIs) and lifestyle modifications. Surveillance with repeated EGD and biopsy is necessary to monitor for early signs of dysplasia.

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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

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

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.

Image by Lecturio.

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
  • 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)

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 findingsManagement
Barrett’s esophagus (metaplasia only)PPIs and EGD every 2–3 years
Low-grade dysplasiaPPIs and EGD every 6–12 months
High-grade dysplasiaEndoscopic ablation or resection (endoscopic or surgical)
Increasing diagnostic accuracy to grade dysplasia in Barrett's esophagus

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×)

Image: “Increasing diagnostic accuracy to grade dysplasia in Barrett’s esophagus” by Karamchandani DM, Lehman HL, Ohanessian SE, Massé J, Welsh PA, Odze RD, Goldblum JR, Berg AS, Stairs DB. License: CC BY 4.0

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

  1. 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
  2. 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
  3. 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
  4. Johnston, M.H., and Eastone, J.A. (2017). Barrett esophagus. In Roy, P.K. (Ed.), Medscape. https://emedicine.medscape.com/article/171002-overview

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