Elsevier

The Lancet

Volume 373, Issue 9666, 7–13 March 2009, Pages 850-861
The Lancet

Seminar
Barrett's oesophagus

https://doi.org/10.1016/S0140-6736(09)60487-6Get rights and content

Summary

Barrett's oesophagus is a metaplastic change of the lining of the oesophagus, such that the normal squamous epithelium is replaced by specialised or intestinalised columnar epithelium. The disorder seems to be a complication of chronic gastro-oesophageal reflux disease, although asymptomatic individuals might also be affected, and it is a risk factor for the development of oesophageal adenocarcinoma, a cancer with rapidly increasing incidence in developed societies. We review the presentation, epidemiology, and risk factors for this condition. We discuss the molecular changes necessary for the development of Barrett's oesophagus and its progression to cancer, and new strides in both the endoscopic detection of the lesion and the treatment of dysplastic disease. Also, we assess the effectiveness of efforts to screen patients at risk of Barrett's oesophagus, and whether such efforts avert cancer death. We conclude with a discussion of future directions for research, focusing on treatment of early neoplasia, and modifications of current practices to show our evolving understanding of this condition.

Introduction

Barrett's oesophagus is a metaplastic change of the lining of the oesophageal mucosa, such that the normal squamous epithelium is replaced with specialised or intestinalised columnar epithelium.1, 2 Intestinal metaplasia is clinically significant because it is associated with heightened risk of oesophageal adenocarcinoma, which has substantially increased in incidence in developed populations. Barrett's oesophagus is associated with symptoms of chronic gastro-oesophageal reflux disease (GERD), such as heartburn and regurgitation.3 This association led to calls for routine upper gastrointestinal endoscopy for all patients with chronic GERD to detect Barrett's oesophagus and prompt subsequent surveillance endoscopies to assess progression to cancer.4 Although such an approach is intuitively appealing, how well screening and surveillance endoscopy works is uncertain, and the associated costs are large and poorly described.5

Section snippets

Clinical presentation

The diagnosis of Barrett's oesophagus should satisfy two criteria.6, 7 First, examination by upper endoscopy should show cephalad displacement of the squamocolumnar junction. Normally, the squamocolumnar junction should coincide with the most distal extent of the tubular oesophagus (figure 1A). The intersection of the squamous epithelium of the tubular oesophagus (figure 1B) and the columnar epithelium of the stomach is termed the Z line, because of the jagged appearance of the interface.

Natural history

The risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus is low, about 0·5% per patient-year,17, 18, 19 and most die with the disorder, not as a result of it. If Barrett's oesophagus does progress, it seems to do so through a series of cellular changes, ranging between non-dysplastic disease, low-grade dysplasia, high-grade dysplasia, and oesophageal adenocarcinoma. Patients with Barrett's oesophagus under endoscopic surveillance who develop cancer often do so without

Epidemiology

Barrett's oesophagus is highly prevalent in the general population and especially in people with chronic reflux conditions, but in some patients the condition is asymptomatic. Policy decisions regarding endoscopic screening and understanding of the cancer risk partly depend on the prevalence of Barrett's oesophagus in the general population. In 1990, the prevalence in Olmsted County, MN, USA, was about 376 cases per 100 000 population, from almost 1000 unselected autopsies.23 This number was

Pathogenesis

Whether Barrett's oesophagus is hereditary is unknown. Several reports suggest that a higher proportion of first-degree relatives of patients with Barrett's oesophagus have the condition than might be expected by chance,39, 44 but no gene has been identified and such data are probably subject to detection bias. The risk of both Barrett's oesophagus and oesophageal adenocarcinoma has long been known to be related to body-mass index (BMI). Increasing BMI is also associated with a statistically

Standard endoscopic screening

Endoscopy is the suggested method for diagnosis, but the results need to be confirmed by histological examination of an endoscopic biopsy specimen. Other methods such as barium study or CT do not have sufficient sensitivity for detection. Patients with chronic reflux symptoms should be screened for Barrett's oesophagus by upper endoscopy only after the patient has been on acid suppression with a proton pump inhibitor for at least 4 weeks. Although pretreatment with a proton pump inhibitor will

Management

Barrett's oesophagus is associated with a decreased quality of life compared with the general population.103 Patients misunderstand and overestimate the cancer rates associated with their condition.104 A US study105 showed that in patients diagnosed with Barrett's oesophagus, despite a life-expectancy similar to age-matched and sex-matched controls, their life-insurance premiums increased by more than 100%. Patients considering endoscopy screening for the condition should be informed of these

Future directions

The best strategy of care for patients with Barrett's oesophagus needs further elucidation. Perhaps most important is the need for risk stratification. Presently, we cannot adequately predict which patients in the large group with chronic heartburn will have the condition, and perhaps more importantly, which patients will progress from Barrett's oesophagus to dysplasia and cancer. The use of histology from endoscopic biopsy samples to assess the degree of dysplasia and risk of cancer is far

Search strategy and selection criteria

We searched Medline (1950–March, 2008), the Cochrane Library (1993–March, 2008), and Embase (1966–March, 2008) using the search terms “Barrett's esophagus” or “Barrett esophagus”, “specialized epithelium”, “columnar-lined esophagus”, and “intestinalized epithelium”. We also searched for “esophageal adenocarcinoma” and “adenocarcinoma of the esophagus” combined with the terms “prevention”, “pathogenesis”, “pathophysiology”, “diagnosis”, and “epidemiology”. No language restrictions were

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