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

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Related Studies

Ontology: Barrett Esophagus (C0004763)

Definition (NCI_NCI-GLOSS) A condition in which the cells lining the lower part of the esophagus have changed or been replaced with abnormal cells that could lead to cancer of the esophagus. The backing up of stomach contents (reflux) may irritate the esophagus and, over time, cause Barrett's esophagus.
Definition (NCI) Esophageal lesion lined with columnar metaplastic epithelium which is flat or villiform. Barrett epithelium is characterized by two different types of cells: goblet cells and columnar cells. The symptomatology of Barrett esophagus is that of gastro-esophageal reflux. It is the precursor of most esophageal adenocarcinomas. (WHO)
Definition (MSH) A condition with damage to the lining of the lower ESOPHAGUS resulting from chronic acid reflux (ESOPHAGITIS, REFLUX). Through the process of metaplasia, the squamous cells are replaced by a columnar epithelium with cells resembling those of the INTESTINE or the salmon-pink mucosa of the STOMACH. Barrett's columnar epithelium is a marker for severe reflux and precursor to ADENOCARCINOMA of the esophagus.
Definition (CSP) syndrome including peptic ulcer of the lower esophagus, often with stricture, due to the presence of columnar lined epithelium, which may contain functional mucous cells, parietal cells, or chief cells in the esophagus instead of normal squamous cell epithelium; sometimes pre-malignant, followed by esophageal adenocarcinoma.
Concepts Disease or Syndrome (T047)
MSH D001471
ICD9 530.85
ICD10 K22.7 , K22.70
SnomedCT 235597001, 196609006, 302914006, 76355008, 155679007, 196603007
LNC LA14288-7
English Esophagus, Barrett, Syndrome, Barrett's, CELLO - Col epith-lin low oeso, CLE - Columnar-lined oeso, Columnar epith-lined low oeso, BO - Barrett's esophagus, Barrett's Esophagus, Barretts Esophagus, Esophagus, Barrett's, Barrett Syndrome, Barrett's Syndrome, Barretts Syndrome, Syndrome, Barrett, Barrett's esophagus (diagnosis), Barrett's oesophagitis, Barrett esophagus, Barrett Esophagus [Disease/Finding], barrett's esophagitis, barrett's esophagus, barretts syndrome, barrett's oesophagitis, barrett's oesophagus, barrett esophagus, barrett's syndrome, barrett syndrome, barrett oesophagitis, barrett esophagitis, Barretts syndrome, Barrett's esophagus NOS, Barrett's disease, Endobrachyoesophagus, BARRETT ESOPHAGUS, BARRETT METAPLASIA, Barretts esophagus, Barrett's esophagitis, Barrett Metaplasia, Barrett's oesophagus (disorder), Endobrachyooesophagus, Columnar-lined esophagus, Barrett's esophagus, Barrett's syndrome, Gastric metaplasia of esophagus, Barrett's oesophagus, Columnar-lined oesophagus, Gastric metaplasia of oesophagus, BO - Barrett's oesophagus, CELLO - Columnar epithelial-lined lower esophagus, CELLO - Columnar epithelial-lined lower oesophagus, CLE - Columnar-lined esophagus, CLE - Columnar-lined oesophagus, Columnar epithelial-lined lower esophagus, Columnar epithelial-lined lower oesophagus, Barrett's esophagus (disorder), Barrett, Barrett's esophagus (disorder) [Ambiguous], Barrett Esophagus, BE, Columnar Epithelial-Lined Lower Esophagus, Columnar-Lined Esophagus, CELLO, CLE, Esophagitis;Barretts, Oesophagitis;Barretts, Barretts esophagitis, Barretts oesophagitis
Dutch Barret-oesophagus, endobrachyoesophagus, Barrett-oesophagitis, Barrett-oesofagitis, Barrett-oesophagus, Barrett-oesofagus, Barrett-syndroom, Oesofagus, Barrett-
French Oesophagite de Barrett, EBO (EndoBrachyOesophage), Endobrachyoesophage, Oesophage de Barrett, Syndrome de Barrett
German Barrett-Oesophagitis, Endobrachyoesophagus, Barrett-Ulkus, Barrett-Syndrom, Barrett-Ösophagus, Ösophagus, Barrett-
Italian Endobrachiesofago, Esofagite di Barrett, Sindrome di Barrett, Esofago di Barrett
Portuguese Endobraquiesófago, Esofagite de Barrett, Esófago de Barrett, Esôfago de Barrett, Síndrome de Barrett
Spanish Endobraquioesófago, Esofagitis de Barrett, síndrome de Barret, epitelio cilíndrico en el esófago distal, esófago distal revestido con epitelio cilíndrico, esófago con epitelio columnar, síndrome de Barrett, metaplasia gástrica de esófago, epitelio columnar en el esófago distal, esófago de Barret (concepto no activo), esófago de Barret (trastorno), esófago de Barret, metaplasia gástrica del esófago, esófago de Barret [dup] (trastorno), Esófago de Barrett, Síndrome de Barrett
Japanese 食道円柱上皮化, バレットショクドウ, ショクドウエンチュウジョウヒカ, Barrett食道, Barrett症候群, バレット食道, バレット症候群, 食道-バレット
Swedish Barretts esofagus
Finnish Barrettin ruokatorvi
Russian BARRETA PISHCHEVOD, PISHCHEVOD BARRETA, БАРРЕТА ПИЩЕВОД, ПИЩЕВОД БАРРЕТА
Czech Endobrachyezofagus, Barretův jícen, Barrettův jícen, Barrettův ezofágus, Barretova ezofagitida
Korean 바렛 식도
Polish Wrzód trawienny przełyku, Przełyk Barretta
Hungarian Barrett oesophagitis, Endobrachyoesophagus, Barrett-oesophagus, Barrett oesophagus, Barrett-oesophagitis
Norwegian Barretts syndrom, Barretts sykdom, Barretts øsofagus, Barretts oesophagus