Barrett’s Syndrome

Barrett's oesophagus (British English: oesophagus) (sometimes called Barrett's syndrome, CELLO, columnar epithelium lined lower esophagus and colloquially referred to as Barrett's) refers to an abnormal change (metaplasia) in the cells of the lower end of the esophagus thought to be caused by damage from chronic acid exposure, or reflux esophagitis. The normal lining of the esophagus (squamous epithelium) is replaced by an intestinal-type lining (columnar epithelium).

Barrett's oesophagus is found in 5-15% of patients who seek medical care for heartburn (gastroesophageal reflux disease, GERD), although a large subgroup of patients with Barrett's esophagus do not have symptoms. It is considered to be a premalignant condition because it is associated with an increased risk of esophageal cancer (more specifically, adenocarcinoma) of about 0.5% per patient-year. Diagnosis of Barrett's esophagus requires endoscopy (more specifically, esophagogastroduodenoscopy, a procedure in which a small tube with a camera at the top is used to look at the esophagus, stomach and first part of the bowels) and biopsy (taking small tissue samples which are analysed using microscopy). The progression from Barrett's esophagus to esophageal cancer is divided into non-dysplastic changes, low-grade and high-grade dysplasia (abnormal cell maturation associated with a risk of progression to cancer) and frank carcinoma. In high-grade dysplasia, the risk of developing cancer might be at 10% per patient-year or greater.

Many professional medical societies propose endoscopic screening of patients with GERD and endoscopic surveillance of patients with Barrett's esophagus, although little direct evidence supports this practice, which is common in many developed countries. Treatment options for high-grade dysplasia include surgical removal of the esophagus (esophagectomy) or endoscopic treatments such as endoscopic mucosal resection or ablation (destruction). Currently, there is no intervention that has been shown to prevent the development of Barrett's esophagus or its progression to esophageal cancer.

The condition is named after Norman Barrett (1903–1979) who described the condition in 1957.

Causes and symptoms

Barrett's esophagus is caused by gastro-oesophageal reflux disease, GORD(USA: GERD), which allows the stomach's contents to damage the cells lining the lower oesophagus. Researchers are unable to predict which heartburn sufferers will develop Barrett's esophagus. While there is no relationship between the severity of heartburn and the development of Barrett's oesophagus, there is a relationship between chronic heartburn and the development of Barrett's esophagus. Sometimes people with Barrett's oesophagus will have no heartburn symptoms at all. In rare cases, damage to the oesophagus may be caused by swallowing a corrosive substance such as lye.

The change from normal to premalignant cells that indicates Barrett's oesophagus does not cause any particular symptoms. However, warning signs that should not be ignored include:

• frequent and longstanding heartburn
• trouble swallowing (dysphagia)
• vomiting blood
• pain under the breastbone where the esophagus meets the stomach
• unintentional weight loss because eating is painful

Treatment

The risk of malignancy is highest in the U.S. in Caucasian men > 50 years of age with > 5 years of symptoms. It is unusual for African-American men to develop adenocarcinoma of the esophagus, the cancer associated with Barrett's. Current recommendations include routine endoscopy and biopsy (looking for dysplastic changes). If two endoscopies and biopsy sessions performed within 12 months are negative for dysplasia then surveillance can be performed every 3 years while the underlying reflux is controlled with proton pump inhibitor drugs in combination with measures to prevent reflux. For patients found to have low grade or high grade dysplasia close observation and repeat endoscopy and biopsies are indicated and the patient should be followed closely by a gastroenterologist.

Proton pump inhibitor drugs have not yet been proven to prevent esophageal cancer. Laser treatment is used in severe dysplasia, while overt malignancy may require surgery, radiation therapy, or systemic chemotherapy. Additionally, a recent 5-year random-controlled trial has shown that photodynamic therapy using photofrin is statistically more effective in eliminating dysplastic growth areas than sole use of a proton pump inhibitor. There is presently no reliable way to determine which patients with Barrett's esophagus will go on to develop esophageal cancer, although a recent study found that the detection of three different genetic abnormalities were associated with as much as a 79% chance of developing cancer in 6 years.

Endoscopic mucosal resection (EMR) has also been evaluated as a management technique. Additionally an operation known as a Nissen fundoplication can reduce the reflux of acid from the stomach into the esophagus.

In a variety of studies, non-steroidal anti-inflammatory drugs (NSAIDS), like aspirin, have shown evidence of preventing esophageal cancer in Barrett's esophagus patients. However, none of these studies have been randomized, placebo controlled trials, which are considered the gold standard for evaluating a medical intervention. In addition, the best dose of NSAIDs for cancer prevention is not yet known.