Synonyms: Barrett's oesophagitis, Barrett's columnar lined oesophagus

Barrett's oesophagus is an acquired condition in which any portion of the normal squamous lining has been replaced by a metaplastic columnar epithelium which is visible macroscopically.

• It is often subdivided into short segment (less than 3 cm) or long segment (more than 3 cm).¹
• A segment of columnar metaplasia of any length must be visible endoscopically above the oesophago-gastric junction and confirmed or corroborated histologically.²
• Barrett's oesophagus results from chronic gastro-oesophageal reflux. The metaplastic columnar epithelium is at risk of increasing grades of dysplasia leading to invasive adenocarcinoma of the oesophagus.³

Epidemiology

• Barrett's oesophagus is found in about 2% of the adult population,⁴ and in 3-5% of persons with gastro-oesophageal reflux disease (GORD).⁵
• It is more common in men and much more common in Caucasians (rare in people of African ancestry). The prevalence increases with age.
• Most cases remain undiagnosed and the prevalence may be much higher than appreciated.
• The development of metaplasia to columnar epithelium does not correlate accurately with the degree of oesophageal acid reflux, and other genetic and environmental factors are clearly involved. Both non-steroidal anti-inflammatory drugs (NSAIDS) - by nonselectively blocking COX receptors⁶ - and Helicobacter pylori⁷ appear to be protective and associated with a lower risk of developing oesophageal adenocarcinoma.

Risk factors

• Patients with chronic GORD are at increased risk of developing the changes of Barrett's oesophagus. The risk increases with longer duration and increased frequency of gastro-oesophageal symptoms.⁸
• Hiatus hernia is a risk factor and the size of the hernia is correlated with the length of Barrett's oesophagus.⁹
• Some studies indicate a higher prevalence of obesity, smoking and alcohol intake.⁹ Risk factors for progression to adenocarcinoma include male gender, age over 45 years, extended segment (>8 cm) disease, duration of reflux history, early age of onset of GORD, duodeno-gastro-oesophageal reflux, mucosal damage (ulceration and stricture) and family history.²

Presentation

• Some patients may not have any symptoms. Symptoms of gastro-oesophageal reflux and strictures are less common in the affected oesophageal segment.
• The classic history is a middle-aged caucasian male with a long history of gastro-oesophageal reflux and, occasionally, dysphagia.¹

Investigations

• Histological corroboration of endoscopically visible columnarisation is the most accurate method of diagnosis.² In cases of erosive oesophagitis, it is important to treat the oesophagitis first to ensure there is no Barrett's mucosa underneath the inflammation.
• When high-grade dysplasia or cancer is found on surveillance endoscopy, endoscopic ultrasound is advisable to evaluate for surgical resectability.¹
• A patient with a columnar-lined distal oesophagus without confirmed intestinal metaplasia on biopsy must be followed up with further endoscopies and biopsies.

Management

• The role of surveillance endoscopy is controversial.^2,4,10 Oesophageal cancers arising in Barrett's oesophagus detected by surveillance are often early and have an excellent prognosis. There are a few studies suggesting that, among patients who develop oesophageal adenocarcinoma, survival is higher in those who had been undergoing endoscopic surveillance.¹¹ It is recommended that when surveillance is considered appropriate, it should be performed every 2 years in the UK.²
• Low-grade dysplasia should be managed by extensive re-biopsy after intensive acid suppression for 8-12 weeks. If persisting, surveillance should be six-monthly for as long as it remains stable. If apparent regression occurs on two consequent examinations, surveillance internals may be increased to 2 yearly.²
• High-grade dysplasia is associated with a focus of invasive adenocarcinoma in 30-40% of patients. Photodynamic therapy appears to be effective in downgrading the dysplasia when used for high-grade dysplasia. However, its efficacy in preventing the progression of Barrett's oesophagus to invasive cancer is not clear.¹²
• If high-grade dysplasia persists after intensive acid suppression, oesophagectomy in a specialised unit is currently recommended in patients considered fit for surgery. In those unfit for surgery, endoscopic ablation or mucosal resection should be considered.^2,12

Nondrug

The recommended lifestyle advice is the same as that recommended for patients with gastro-oesophageal reflux disease.

• Reduce weight.
• Stop smoking.
• Reduce alcohol intake.
• Raise the head of the bed at night.
• Take small, regular meals.
• Avoid hot drinks, alcohol, and eating within 3 hours of going to bed.
• Avoid drugs that affect oesophageal motility (nitrates, anticholinergics, tricyclic antidepressants) or damage the mucosa (NSAIDs, potassium salts, alendronate).

Drug

• Available data indicate that long-term proton pump inhibitor (PPI) therapy is effective. Twice-daily PPI therapy may be recommended for patients who do not respond clinically to once-daily therapy. There are no studies that provide evidence that higher doses of PPI therapy provide any increased benefit for prevention of oesophageal adenocarcinoma.¹
• Recent review of data indicates that chemoprevention with aspirin (AspECT trial) may be the most promising approach for reduction of adenocarcinoma risk, previous studies having shown a protective association between NSAIDs and oesophageal cancer.¹³
• Ablative therapy.¹² The goal of ablative therapy is to destroy the Barrett's epithelium to a sufficient depth to eliminate the intestinal metaplasia and allow regrowth of squamous epithelium. A number of modalities have been tried, e.g. photodynamic therapy, argon plasma coagulation, multipolar electrocoagulation and various forms of lasers. There is no direct evidence to suggest that there is a reduction in cancer risk in patients after mucosal ablation therapy. Long-term outcomes have been disappointing in terms of relapse after treatment, but this form of treatment is still considered to offer the prospect of developing improved intervention for the future.¹⁴

Surgical

• Anti-reflux surgeries, e.g. Nissen's fundoplication, have not been shown to prevent the progression of Barrett's oesophagus to oesophageal cancer.¹
• However oesophagectomy is often recommended when severe dysplasia is confirmed.¹⁵

Complications

• The most significant complication is the development of adenocarcinoma in the oesophagus. Recent data suggest that the risk of dysplasia is strongly associated with increasing age of the patient and the segment length of Barrett's oesophagus.¹⁶ The incidence of adenocarcinoma is rising, with current rates in Scotland being the highest reported rates in the world⁴
• Although Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma, most patients with Barrett's oesophagus do not develop cancer.¹⁷
• Barrett's oesophagus has a 2-25% risk of mild-severe dysplasia and a lifetime risk of developing adenocarcinoma of 3% in women and 5% in men.⁴ 40-50% of those patients with Barrett's oesophagus and severe dysplasia go on to develop oesophageal adenocarcinoma within 5 years.¹⁴

Prognosis

• Barrett's oesophagus is a premalignant condition and increases the risk of oesophageal adenocarcinoma to 30-60 times that of the general population.¹⁸
• Most patients will not develop oesophageal cancer and will die of other causes.
• In a cohort study of patients with Barrett's oesophagus but not undergoing surveillance, only 2.5% of 155 patients died as a result of oesophageal cancer, with a mean of 9 years' follow-up.¹

Screening

Endoscopic surveillance for patients with Barrett's is described above.

Should patients with heartburn be screened for Barrett's?

Chronic heartburn is a risk factor for oesophageal adenocarcinoma and the risk increases with increasing severity and duration of heartburn. However, the absolute risk in individual patients is less than 1 in 1,000 per annum and there is no evidence that endoscopic screening of heartburn patients to detect cancer is worthwhile.²

However, in view of the increasing incidence of oesophageal adenocarcinoma, the poor results of treatment for established adenocarcinoma and the likely development of better diagnostic tools in the future, screening may be considered worthwhile in the future.¹⁹

Document references

1. Sharma P, McQuaid K, Dent J, et al; A critical review of the diagnosis and management of Barrett's esophagus: the AGA Chicago Workshop. Gastroenterology. 2004 Jul;127(1):310-30. [abstract]
2. Guidelines for the diagnosis and management of Barrett's columnar-lined oesophagus, British Society of Gastoenterology (BSG), August 2005
3. Flejou JF; Barrett's oesophagus: from metaplasia to dysplasia and cancer. Gut. 2005 Mar;54 Suppl 1:i6-12. [abstract]
4. Jankowski J, Barr H, Wang K, et al; Diagnosis and management of Barrett's oesophagus. BMJ. 2010 Sep 10;341:c4551. doi: 10.1136/bmj.c4551.
5. Cameron AJ; Epidemiology of columnar-lined esophagus and adenocarcinoma. Gastroenterol Clin North Am. 1997 Sep;26(3):487-94. [abstract]
6. Fitzgerald RC; Barrett's oesophagus and oesophageal adenocarcinoma: how does acid interfere with cell proliferation and differentiation? Gut. 2005 Mar;54 Suppl 1:i21-6. [abstract]
7. Malfertheiner P, Peitz U; The interplay between Helicobacter pylori, gastro-oesophageal reflux disease, and intestinal metaplasia. Gut. 2005 Mar;54 Suppl 1:i13-20. [abstract]
8. Lieberman DA, Oehlke M, Helfand M; Risk factors for Barrett's esophagus in community-based practice. GORGE consortium. Gastroenterology Outcomes Research Group in Endoscopy. Am J Gastroenterol. 1997 Aug;92(8):1293-7. [abstract]
9. Avidan B, Sonnenberg A, Schnell TG, et al; Hiatal hernia and acid reflux frequency predict presence and length of Barrett's esophagus. Dig Dis Sci. 2002 Feb;47(2):256-64. [abstract]
10. Streitz JM Jr, Andrews CW Jr, Ellis FH Jr; Endoscopic surveillance of Barrett's esophagus. Does it help? J Thorac Cardiovasc Surg. 1993 Mar;105(3):383-7; discussion 387-8. [abstract]
11. Sampliner RE; Ablative therapies for the columnar-lined esophagus. Gastroenterol Clin North Am. 1997 Sep;26(3):685-94. [abstract]
12. Barrett's oesophagus - ablative therapy, NICE Clinical Guideline (August 2010); Ablative therapy for the treatment of Barrett's oesophagus
13. Corley DA, Kerlikowske K, Verma R, et al; Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology. 2003 Jan;124(1):47-56. [abstract]
14. Deviere J; Barrett's oesophagus: the new endoscopic modalities have a future. Gut. 2005 Mar;54 Suppl 1:i33-7. [abstract]
15. Schuchert MJ, Luketich JD; Management of Barrett's esophagus. Oncology (Williston Park). 2007 Oct;21(11):1382-9, 1392; discussion 1392, 1394, 1396. [abstract]
16. Gopal DV, Lieberman DA, Magaret N, et al; Risk factors for dysplasia in patients with Barrett's esophagus (BE): results from a multicenter consortium. Dig Dis Sci. 2003 Aug;48(8):1537-41. [abstract]
17. Spechler SJ, Lee E, Ahnen D, et al; Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial. JAMA. 2001 May 9;285(18):2331-8. [abstract]
18. Lagergren J; Adenocarcinoma of oesophagus: what exactly is the size of the problem and who is at risk? Gut. 2005 Mar;54 Suppl 1:i1-5. [abstract]

Internet and further reading

• Guidelines for the diagnosis and management of Barrett's columnar-lined oesophagus, British Society of Gastroenterology (2005)
• Photodynamic therapy for Barrett's oesophagus, NICE Interventional Procedure Guideline (June 2010)

Acknowledgements