Barrett's oesophagus

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

What is Barrett's oesophagus?^{1 2}

Barrett's oesophagus is defined as an oesophagus in which any portion of the normal distal squamous epithelial lining has been replaced by metaplastic columnar epithelium, which is clearly visible endoscopically (>1 cm) above the gastro-oesophageal junction and confirmed histopathologically from oesophageal biopsies.

• It is often subdivided into short-segment (less than 3 cm) or long-segment (more than 3 cm).

• 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

How common is Barrett's oesophagus? (Epidemiology)⁴

• • The exact prevalence in different populations is difficult to assess as the condition is asymptomatic, and a diagnosis is made only when an endoscopy is performed. Most cases remain undiagnosed and the prevalence may be much higher than appreciated.

  • The prevalence of Barrett’s oesophagus in the unselected general population is between 1% and 2% in European studies and approximately 5-6% in the USA.

  • 
    The prevalence is estimated to be as high as 15% in those with gastro-oesophageal reflux disease (GORD).

• It is more common in men and much more common in Caucasians (rare in people of African ancestry). The prevalence increases with age and it is more likely to affect those with a positive family history of the condition.⁵

• UK studies on age- and sex-related distribution of Barrett’s oesophagus prevalence have observed that the prevalence of Barrett’s oesophagus increased with 7.4% for each additional year of age between the age of 20 and 59 years in males. There was a similar pattern though with a 20-year delay in the female population.

• 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.

Risk factors^{6 7 8}

Risk factors include:

• Male sex.

• Long duration and/or increased frequency of GORD symptoms.

• Previous oesophagitis or hiatus hernia.

• Previous oesophageal stricture or ulcers.

• Risk factors for progression to adenocarcinoma include male gender, increasing age, extended segment (>8 cm) disease, intestinal metaplasia, duration of reflux history, early stages of onset of GORD, duodeno-gastro-oesophageal reflux, mucosal damage (ulceration and stricture) and family history.^{1 9}

Barrett's oesophagus symptoms¹

• 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 long history of gastro-oesophageal reflux and, occasionally, dysphagia.

Investigations¹

• Histological corroboration of endoscopically visible columnarisation is the most accurate method of diagnosis. In cases of erosive oesophagitis, it is important to treat the oesophagitis first to ensure there is no Barrett's mucosa underneath the inflammation.

• A patient with a columnar-lined distal oesophagus without confirmed intestinal metaplasia on biopsy must be followed up with further endoscopies and biopsies.

Barrett's oesophagus treatment and management¹

Endoscopic surveillance¹⁰

• High resolution white light endoscopic surveillance with Seattle protocol biopsies should be offered:

  • Every 2-3 years to people with long-segment (3 cm or longer) Barrett's oesophagus.

  • Every 3-5 years to people with short-segment (less than 3 cm) Barrett's oesophagus with intestinal metaplasia.

• Assess a person's risk of cancer based on their age, sex, family history of oesophageal cancer and smoking history and tailor the frequency of endoscopic surveillance accordingly.

• Do not offer endoscopic surveillance to people with short-segment (less than 3 cm) Barrett's oesophagus without intestinal metaplasia provided the diagnosis has been confirmed at two endoscopies.

Oesophageal cancers arising in Barrett's oesophagus detected by surveillance are often early and have an excellent prognosis.

Non-drug treatment for Barrett's oesophagus

The recommended lifestyle advice is the same as that recommended for patients with GORD:

• 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 three hours of going to bed.

• Avoid drugs that affect oesophageal motility (nitrates, anticholinergics, tricyclic antidepressants) or damage the mucosa (NSAIDs, potassium salts, alendronate).

Drug treatment for Barrett's oesophagus

• 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.

• Aspirin should not be offered to people with Barrett's oesophagus to prevent progression to oesophageal dysplasia and cancer.¹⁰

Endoscopic eradication therapy is now widely used for the treatment of Barrett's oesophagus-related neoplasia.¹¹ However a Cochrane review found that there are no randomised controlled trials to compare surgery with radical endotherapies for early cancer and high-grade dysplasia in Barrett's oesophagus.¹²

Ablative therapy¹³

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 - eg, photodynamic therapy, argon plasma coagulation, multipolar electrocoagulation and various forms of lasers.

Endoscopic radiofrequency ablation
Evidence on the efficacy of endoscopic radiofrequency ablation for Barrett's oesophagus with low-grade dysplasia is adequate provided that patients are followed up in the long term. There are no major safety concerns.¹⁴

Epithelial radiofrequency ablation¹⁵
Current evidence on the efficacy of epithelial radiofrequency ablation in patients with Barrett's oesophagus with high-grade dysplasia is adequate, provided that patients are followed up in the long term. There are no major safety concerns.

Photodynamic therapy¹³
Current evidence on the efficacy of photodynamic therapy (PDT) for patients with Barrett's oesophagus with high-grade dysplasia is adequate, provided that patients are followed up in the long term. There are no major safety concerns, although there is a risk of oesophageal stricture, and photosensitivity reactions are common.

Current evidence on the efficacy and safety of PDT in patients with Barrett's oesophagus with either low-grade dysplasia or no dysplasia is inadequate and the balance of risks and benefits is not clear.

Balloon cryotherapy¹⁶

The National Institute for Health and Care Excellence (NICE) has issued new guidance on the use of balloon cryoablation for Barrett's oesophagus. It recommends that there is inadequate evidence on the safety and efficacy of this procedure.

Balloon cryotherapy should, therefore, only be used in the context of research, and patient selection should be carried out by clinicians experienced in managing Barrett's oesophagus.

NICE guidance¹⁰

• Offer endoscopic resection of visible oesophageal lesions as first-line treatment to people with high-grade dysplasia.

• Offer endoscopic ablation of any residual Barrett's oesophagus to people with high-grade dysplasia after treatment with endoscopic resection.

• Offer radiofrequency ablation to people with low-grade oesophageal dysplasia diagnosed from biopsies taken at two separate endoscopies. Two gastrointestinal pathologists should confirm the histological diagnosis.

• Consider endoscopic surveillance at six-monthly intervals with dose optimisation of acid-suppressant medication for people diagnosed with indefinite dysplasia of the oesophagus.

• Offer endoscopic follow-up to people who have received endoscopic treatment for Barrett's oesophagus with dysplasia.

Follow the NICE interventional procedures guidance on endoscopic radiofrequency ablation for Barrett's oesophagus with low-grade dysplasia or no dysplasia and epithelial radiofrequency ablation for Barrett's oesophagus.

Anti-reflux surgery
Anti-reflux surgery should not be offered to people with Barrett's oesophagus to prevent progression to dysplasia or cancer. However, surgery may be required for gastro-oesophageal reflux disease and dyspepsia.

Complications⁹

• 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. However, most patients with Barrett's oesophagus do not develop oesophageal cancer.

• The incidence of adenocarcinoma is rising, with current rates in Scotland being the highest reported rates in the world.

• 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. 40-50% of those patients with Barrett's oesophagus and severe dysplasia go on to develop oesophageal adenocarcinoma within five years.

Prognosis

• Barrett's oesophagus is a pre-malignant condition and increases the risk of oesophageal adenocarcinoma.

• However, most patients will not develop oesophageal cancer and will die of other causes.¹⁷

• 5-10% of those with Barrett's oesophagus will develop adenocarcinoma over 10-20 years.⁸

Screening¹

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

Should patients with heartburn be screened for Barrett's oesophagus?

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. The latest BSG guidelines recommend that:

• Screening with endoscopy is not feasible or justified for an unselected population with gastro-oesophageal reflux symptoms.

• Endoscopic screening can, however, be considered in patients with chronic GORD symptoms and multiple risk factors (at least three of age 50 years or older, white race, male sex, obesity).

• The threshold of multiple risk factors should, however, be lowered in the presence of a family history including at least one first-degree relative with Barrett's oesophagus or oesophageal adenocarcinoma.

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, screening may be considered worthwhile in the future.