Barrett Esophagus

Aka: Barrett Esophagus, Barrett's Esophagus, Barrett Metaplasia, Columnar Epithelial-Lined Lower Esophagus

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II. Epidemiology

  1. U.S. Prevalence: 1.2 to 1.6% (up to 5 to 6% by computer modeling)

III. Definitions

  1. Barrett Esophagus
    1. Premalignant precursor to Esophageal Adenocarcinoma
    2. Chronic Reflux Esophagitis leads to metaplastic columnar cells replacing the normal esophageal squamous epithelium

IV. Pathophysiology

  1. Metaplasia
    1. Columnar metaplasia of distal Esophagus (from normal squamous cell lining)
  2. Response to chronic inflammation from gastric acidic fluid via lower esophageal sphincter
    1. Gastroesophageal Reflux
  3. Precancerous lesion
    1. Metaplasia progresses to Esophageal Adenocarcinoma in 0.24% to 0.33% of patients with Barrett Esophagus annually
    2. Overall Esophageal Adenocarcinoma is rare (1% of U.S. cancers)

V. Risk Factors

  1. Precautions
    1. Two or more positive risk factors significantly increase Barrett Esophagus risk
  2. Gastroesophageal Reflux
    1. GERD Symptoms
      1. Chronic GERD symptoms progresses to Barrett Esophagus in up to 10% of patients
      2. Reported symptoms > 3x/week for 20 years: RR = 40
      3. Self report weekly symptoms for prior year: OR = 29.7
    2. GERD duration
      1. Persisted >10 years: Odds Ratio 6.4
      2. Persisted 5-10 years: Odds Ratio 5.0
      3. Persisted 1-5 years: Odds Ratio 3.0
    3. Increases risk of long-segment Barrett Esophagus
    4. Onset of GERD before age 30 years: Odds Ratio 15.1
    5. However, overall only a small percentage of those with GERD develop Barrett Esophagus
    6. Up to half of patients in some studies are asymptomatic of Barrett Esophagus
      1. Sharma (2009) N Engl J Med 361(26): 2548-56 [PubMed]
  3. Caucasian (as opposed to asian, hispanic and black patients)
  4. Hiatal Hernia
  5. Family History of Barrett Esophagus
  6. Age over 40-50 years old
    1. Age >40 (OR=4.9)
    2. Risk is even greater at age > 50 years old
  7. Tobacco Abuse
    1. Two fold increase in Esophageal Cancer with a 30 or 45 pack year history of Tobacco Abuse
    2. Odds Ratio 2.4 (former or current Tobacco Abuse)
    3. Odds Ratio 51.4 if patient with Tobacco Abuse self-reports weekly Acid Reflux symptoms
    4. Alcohol does not appear to increase Barrett Esophagus risk
  8. Male gender
    1. Odds Ratio 3.7
  9. Obesity (BMI >30 kg/m2)
    1. Odds Ration 4.0 regardless of symptoms
    2. Odds Ratio 34.4 if obese patient self-reports weekly Acid Reflux symptoms

VI. Evaluation: Endoscopy

  1. Indications for screening for Barrett's Esophagus
    1. Significant risk factors above
      1. See GERD related indications as below
    2. Red flag symptoms
      1. Dysphagia
      2. Odynaphagia or obstruction
      3. Upper Gastrointestinal Bleeding or Anemia
      4. Weight loss
      5. Symptoms refractory to Proton Pump Inhibitors
  2. Surveillance and management protocol (controversial)
    1. Guidelines are per American College of Gastroenterology, and correlate overall with other organizations
      1. American Society of Gastrointestinal Endoscopy
      2. American College of Physicians
      3. American Gastroenterological Association
    2. GERD
      1. GERD without risk factors does not require upper endoscopy
      2. Consider screening once in patients with chronic or frequent GERD with multiple risk factors
        1. Consider especially if GERD refractory to standard management (unless findings change)
        2. Avoid screening if Life Expectancy <10 years
        3. Men: Age >50 years and at least one other risk factor
        4. Women: Age >50 years and at least two or more other risk factors
    3. Barrett's Esophagus without dysplasia
      1. Repeat endoscopy with biopsy in one year
      2. If no dysplasia x2 biopsies, then endoscopy every 3-5 years
        1. If no significant comorbidities, may continue surveillance, until age 81 years in men age 75 years in women
        2. Avoid surveillance when Life Expectancy <5 years
    4. Low grade dysplasia
      1. Consider endoscopic treatment with ablation (NNT 10, see management below)
      2. Repeat endoscopy with biopsy in 6 months
      3. Then repeat upper endoscopy yearly until no dysplasia on 2 biopsies (and then endoscopy every 3 years)
    5. High grade dysplasia (or intramural carcinoma)
      1. Endoscopic treatment for dysplasia (see management below)
      2. Repeat upper endoscopy every 3 months for 1 year, then every 6 months for 1 year, then yearly
      3. Consider esophagectomy if able to undergo surgery
      4. Consider endoscopic resection and ablation if not able to undergo surgery
    6. References
      1. Wang (2008) Am J Gastroenterol 103(3): 788-97 [PubMed]
  3. Findings consistent with Barrett's Esophagus
    1. Z-line is squamocolumnar junction
      1. Z-Line is normally at gastroesophageal junction
    2. Barrett's Esophagus
      1. Normal pale-white esophageal mucosa appears salmon colored on endoscopy
        1. Esophageal biopsy demonstrates columnar epithelium with goblet cells (metaplasia)
      2. Z-line shifts up from gastroesophageal junction (at least 1 cm above gastric folds)
        1. Long-segment Barrett's: >3 cm from junction
        2. Short-segment Barrett's: <3 cm from junction
  4. Screening difficulties
    1. Endoscopy Complications (1 in 200 to 10,000)
      1. Esophageal Perforation or bleeding
      2. Cardiopulmonary events
      3. Adverse effects from sedation (e.g. Aspiration Pneumonitis)
    2. Esophageal Cancer is uncommon, even in Barrett Esophagus
    3. Most Esophageal Cancer patients have no GERD symptoms
    4. Surveillance results in earlier stage Esophageal Cancer diagnosis, but does not lower all cause mortality
    5. References
      1. Codipilly (2018) Gastroenterology 154(8): 2068-86 [PubMed]
      2. Gopal (2002) Evid Based Oncol 3(4):144-5 [PubMed]
      3. Hage (2004) Scand J Gastroenterol 39:1175-9 [PubMed]

VII. Management

  1. Proton Pump Inhibitor or PPI (e.g. Prilosec, Protonix) Long-term
    1. High dose (e.g. Esomeprazole 40 mg) may be preferred over low dose (e.g. Esomeprazole 20 mg)
      1. Jankowski (2018) Lancet 392(10145): 400-8 [PubMed]
    2. Antireflux Surgery is no better than PPI is prevention of Barrett Esophagus progression to adenocarcinoma
      1. Corey (2003) Am J Gastroenterol 98(11): 2390-94 [PubMed]
  2. High grade dysplasia
    1. Noninvasive methods (Endoscopic Treatment)
      1. Noninvasive treatment methods may also be considered in low grade dysplasia
      2. Photodynamic therapy
        1. Systemic Photosensitizers administered followed by endoscopic exposure to laser light
        2. Complete response in >78% of cases
        3. Only treatment that significantly reduces Barrett Esophagus progression to cancer
        4. Risk of Esophageal Stricture in 33%
      3. Radiofrequency Ablation
        1. Balloon placed adjacent to mucosal lesions and providers localized thermal ablation
        2. Complete response in >91% of cases
        3. Risk of Esophageal Stricture 6-8%, bleeding 1% and perforation 0.6%
      4. Endoscopic mucosal resection
        1. Complete response in >76% of cases
        2. Preferred method for endoscopic cancer staging of nodular lesions
        3. Also indicated in the treatment of T1a (mucosal invasion) Esophageal Adenocarcinoma lesions
        4. Risk of Esophageal Stricture in >50% (as well as bleeding and perforation)
    2. Invasive methods
      1. Esophagectomy
  3. Other measures
    1. Small decrease in Esophageal Cancer associated with those on Aspirin (or NSAID), or on a Statin
      1. Aspirin and Statin may be considered if indicated for other indication
      2. Jankowski (2018) Lancet 392(10145): 400-8 [PubMed]
      3. Thomas (2018) J Gastrointest Cancer 49(4): 442-54 [PubMed]

VIII. Prognosis: Endoscopy factors predicting low risk of adenocarcinoma

  1. Low grade or no dysplasia on initial endoscopy and
  2. Barrett's Esophagus length <6 cm
  3. Weston (2004) Am J Gastroenterol 99:1657-66 [PubMed]

IX. Complications: Barrett's Esophagus progression to Esophageal Adenocarcinoma

  1. Metaplasia progresses to Esophageal Adenocarcinoma in <0.5% of patients with Barrett Esophagus annually
  2. Most Barrett Esophagus patients (93%) die from causes other than Esophageal Adenocarcinoma
    1. Sikkema (2010) Clin Gastroenterol Hepatol 8(3): 235-44 [PubMed]
  3. Relative Risk of adenocarcinoma with Barrett Esophagus: 11.3
  4. Lifetime risk of requiring an intervention for high grade dysplasia or Esophageal Adenocarcinoma: 1 in 5 (or 6)
  5. Risk increases with longer segment Barrett Esophagus (1.1 RR/cm over 2 cm)
    1. Long segment nondysplastic Barrett Esophagus: 0.33% cancer Incidence per year
    2. Short segment nondysplastic Barrett Esophagus: 0.19% cancer Incidence per year
  6. Risk increases with dysplasia on biopsy
    1. No dysplasia: 1 case per 1000 patient-years (0.1 to 0.33% per year)
    2. Low grade dysplasia: 5 cases per 1000 patient-years (0.5% per year)
    3. High grade dysplasia: 42 cases per 1000 patient-years (7% per year)
  7. Other factors with increased risk
    1. Duration of symptoms >10 years
    2. Esophagitis on upper endoscopy

X. References

  1. Kahrilas in Feldman (2002) Sleisenger GI, p. 615-8
  2. Bryce (2022) Am Fam Physician 106(4): 383-7 [PubMed]
  3. Katzka (2003) Hematol Oncol Clin North Am 17(2):471 [PubMed]
  4. Sharma (2009) N Engl J Med 361(26): 2548-56 [PubMed]
  5. Smith (2005) Cancer Epidemiol Biomarkers Prev 14(11 pt 1): 2481-6 +PMID:16284367 [PubMed]
  6. Spechler (2002) N Engl J Med 346:836-42 [PubMed]
  7. Zimmerman (2014) Am Fam Physician 89(2): 92-8 [PubMed]

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