Barrett Esophagus

See Also

Gastroesophageal Reflux Disease
Esophageal Adenocarcinoma

Epidemiology

Prevalence: 1.2 to 1.6%

Pathophysiology

Metaplasia
1. Columnar metaplasia of distal esophagus (from normal squamous cell lining)
Response to chronic inflammation from gastric acidic fluid via lower esophageal sphincter
1. Gastroesophageal Reflux
Precancerous lesion
1. Metaplasia progresses to Esophageal Adenocarcinoma in <0.33% of patients with Barrett Esophagus annually

Risk Factors

Precautions
1. Two or more positive risk factors significantly increase Barrett Esophagus risk
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. However, overall only a small percentage of those with GERD develop Barrett Esophagus
5. 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]
Caucasian (as opposed to asian, hispanic and black patients)
Hiatal Hernia
Age over 40-50 years old
1. Age >40 (OR=4.9)
2. Risk is even greater at age > 50 years old
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
Male gender
1. Odds Ratio 3.7
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

Evaluation
Endoscopy

Indications for screening for Barrett's Esophagus
1. Significant risk factors above
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
Surveillance and management protocol (controversial)
1. Guidelines are per American College of Gastroenterology
  1. Overall correlate with American Society of Gastrointestinal Endoscopy, American College of Physicians, American Gastroenterological Association
2. GERD
  1. Consider screening only once in patients with GERD with multiple risk factors or refractory to standard management (unless findings change)
  2. GERD without risk factors does not require upper endoscopy
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
4. Low grade dysplasia
  1. Repeat endoscopy with biopsy in 6 months
  2. Then repeat upper endoscopy annually until no dysplasia on 2 biopsies (and then endoscopy every 3 years)
5. High grade dysplasia
  1. Repeat upper endoscopy every 3 months
  2. Consider esophagectomy if able to undergo surgery
  3. Consider endoscopic resection and ablation if not able to undergo surgery
6. References
  1. Wang (2008) Am J Gastroenterol 103(3): 788-97 [PubMed]
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. Z-line shifts up from gastroesophageal junction
  2. Long-segment Barrett's: >3 cm from junction
  3. Short-segment Barrett's: <3 cm from junction
Screening difficulties
1. Esophageal Cancer is uncommon, even in Barrett's
2. Most Esophageal Cancer patients have no GERD symptoms
3. Longterm surveillance is still recommended
4. References
  1. Gopal (2002) Evid Based Oncol 3(4):144-5 [PubMed]
  2. Hage (2004) Scand J Gastroenterol 39:1175-9 [PubMed]

Management

Proton Pump Inhibitor (e.g. Prilosec, Protonix) Long-term
High grade dysplasia
1. Noninvasive methods
  1. 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%
  2. 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 <8%
  3. Endoscopic mucosal resection
    1. Complete response in >76% of cases
    2. Preferred method for endoscopic cancer staging
    3. Risk of Esophageal Stricture in >50% (as well as bleeding and perforation)
2. Invasive methods
  1. Esophagectomy

Prognosis
Endoscopy factors predicting low risk of adenocarcinoma

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

Complications
Barrett's Esophagus progression to Esophageal Adenocarcinoma

Metaplasia progresses to Esophageal Adenocarcinoma in <0.5% of patients with Barrett Esophagus annually
Relative Risk of adenocarcinoma with Barrett Esophagus: 11.3
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
Risk increases with dysplasia on biopsy
1. No dysplasia: 1 case per 1000 patient-years
2. Low grade dysplasia: 5 cases per 1000 patient-years
3. High grade dysplasia: 42 cases per 1000 patient-years
Other factors with increased risk
1. Duration of symptoms >10 years
2. Esophagitis on upper endoscopy

References

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