Barrett’s Esophagus

Abstract

The prevalence of Barrett’s esophagus is increasing in the United States and is a major risk factor for esophageal adenocarcinoma. This review serves to help primary care physicians and family practitioners better understand who should be screened for Barrett’s esophagus, know the appropriate surveillance intervals for repeat endoscopy, and understand therapeutic options for the management of Barrett’s esophagus.

Chronic reflux esophagitis leads to the development of Barrett’s esophagus; who and when to conduct surveillance for adenocarcinoma in patients with Barrett’s remains controversial.

Introduction

Gastroesophageal reflux disease (GERD) is highly prevalent in the United States and complaints related to gastroesophageal reflux disease constitute a large proportion of the primary care physicians’ practice.¹ However, only a small proportion of patients with GERD are at risk of developing Barrett’s esophagus (BE).² Barrett’s esophagus is a pre-malignant condition that places patients at risk for esophageal adenocarcinoma (EAC).³ Within the last decade, our understanding of the pathogenesis of Barrett’s esophagus has increased substantially, with improved risk stratification to identify patients who are at risk for progression to esophageal adenocarcinoma. Equally impressive is the ever-expanding endoscopic armamentarium to treat dysplastic lesions, obviating the need for more invasive therapies such as esophagectomy. Discerning which patients should be referred for BE screening and surveillance will enable optimization of treatment regimens for Barrett’s esophagus.

Definition of Barrett’s

Barrett’s esophagus occurs when the normal squamous epithelium of the distal esophagus changes to columnar-lined intestinal type cells, a transition known as intestinal metaplasia. Its importance lies in that it is the only known precursor to esophageal adenocarcinoma.⁴ The transition occurs when the esophagus is repeatedly exposed to gastric acid, which in turn causes mucosal inflammation. When intestinal metaplasia occurs, the normal esophageal mucosa will take on a salmon colored appearance when viewed endoscopically (Figure 1: Panel A and B). When this is seen and is greater than one centimeter in length, endoscopic biopsies should be obtained to determine if goblet cells or dysplasia are seen on histological review. The diagnostic criteria for Barrett’s esophagus that goblet cells are present is controversial, but is the accepted practice in the United States.⁴ Patients with intestinal metaplasia less than one centimeter in length do not have an increased risk for further complications. Unfortunately, there is a great deal of inter-observer variability in the histologic interpretation of dysplasia and the diagnosis should be confirmed by two pathologists, one of whom has extensive experience in the interpretation of Barrett’s-associated neoplasia.²

Figure 1.

A, Endoscopic view of salmon-colored mucosa typical of Barrett’s esophagus in white light; B, Narrow band imaging highlighting the squamous cell epithelium (white mucosa) and tongues and islands of Barrett’s mucosa (arrows); C, Burned patch of esophageal mucosa after one session of radiofrequency ablation (white colored mucosa).

Risk Factors

Although gastroesophageal reflux disease is highly prevalent in the United States, only 10–15% of patients with gastroesophageal reflux disease will develop Barrett’s esophagus and up to 50% of subjects with Barrett’s or esophageal adenocarcinoma will report no history of gastroesophageal reflux symptoms.² Overall, Barrett’s esophagus affects 2–7% of adults in western countries.⁴ Shown in Table 1 are the known risk factors for Barrett’s esophagus and esophageal adenocarcinoma.²

Table 1.

Risk Factors for Barrett’s Esophagus

Risk Factors for Barrett’s Esophagus
Caucasian race
Male
Age > 50
Central obesity (waist circumference >102 cm)
History of GERD
Smoking history
Family history of Barrett’s esophagus
Esophageal adenocarcinoma in a first-degree relative

Current guidelines by the American College of Gastroenterology recommend screening only men with frequent gastroesophageal reflux disease (at least weekly symptoms or symptoms that have persisted more than five years) and two or more of the known risk factors. Routine screening of women is not recommended except those with multiple risk factors and a documented family history of Barrett’s esophagus or esophageal adenocarcinoma in a first-degree relative.

Natural History

The incidence of esophageal adenocarcinoma has increased substantially over the past four decades with an estimated incidence of 2.8 cases per 100,000 in the United States.³ Esophageal adenocarcinoma in Barrett’s esophagus develops through a progressive sequence of histologic and molecular events that begin with metaplasia and then progresses through various stages of dysplasia before development of adenocarcinoma.⁴ The specific cell type at the squamocolumnar junction responsible for the development of Barrett’s was recently described.⁵ Dysplasia is defined as neoplastic epithelium that is confined to the basement membrane and the use of the descriptors low grade or high grade is based upon the severity of architectural distortion seen histologically. Advancing age, increasing Barrett’s segment length, and endoscopic irregularities of the mucosa (e.g. nodules, ulcers) are risk factors for dysplasia. The risk of esophageal adenocarcinoma is proportional to the degree of dysplasia and survival in esophageal adenocarcinoma is stage dependent.⁶ Malignant progression in patients with non-dysplastic Barrett’s is low with an annual incidence of 0.33% per year,² however, Barrett’s esophagus with high grade dysplasia has an annual incidence rate of 7% for developing EAC.⁷ Unfortunately, more than 90% of diagnosed esophageal adenocarcinoma cases occur in patients without a prior history of Barrett’s esophagus.² Nevertheless, given the low five year survival rates of patients with esophageal adenocarcinoma, screening and surveillance strategies have been proposed to decrease rates of EAC.

Therefore, the best hope for survival in esophageal adenocarcinoma remains endoscopic screening and surveillance of Barrett’s esophagus patients to detect dysplasia and esophageal adenocarcinoma at an early stage where potentially curable interventions exist.² Patients with esophageal adenocarcinoma detected in a surveillance program have their cancers detected at an earlier stage with markedly improved five-year survival compared with similar patients not undergoing routine surveillance.⁶ However, only 7% of patients with Barrett’s esophagus die of esophageal adenocarcinoma. Most will die of non-intestinal causes such as heart disease and pulmonary disease.²

Treatment of Barrett’s Esophagus

All patients with Barrett’s esophagus should be on once daily proton pump inhibitor therapy as this may reduce the risk of progression to dysplasia and esophageal adenocarcinoma. The use of H2 blockers has not shown to reduce this risk. Twice daily dosing is not routinely recommended and should only be used for poorly controlled gastroesophageal reflux disease or evidence of persistent inflammation. Currently there is not enough evidence to advocate the use of medications such as statins, aspirin or non-steroidal anti-inflammatory drugs as a chemoprevention strategy. Antireflux surgery should not be recommended for treatment of Barrett’s alone but may be considered for GERD management.

Surveillance endoscopy intervals are currently determined by the presence and grade of dysplasia. As the risk is low for esophageal adenocarcinoma in patients with non-dysplastic Barrett’s esophagus, surveillance upper endoscopy with biopsies should occur every three to five years in these patients. Patients with low or high-grade dysplasia or stage T1a esophageal adenocarcinoma (defined as being limited to the mucosa with no extension to the submucosa) should be managed with endoscopic therapy. Endoscopic management has been shown in multiple randomized controlled trials to effectively eliminate dysplastic and metaplastic epithelium, as well as greatly reduce cancer incidence.⁴ Currently the preferred endoscopic therapy for low grade dysplasia is radiofrequency ablation (Figure 1, Panel C). Radiofrequency ablation has largely replaced most other forms of ablation such as argon plasma coagulation and photodynamic therapy because of its high efficacy rate and low complication rate. For patients with high-grade dysplasia or stage T1a esophageal adenocarcinoma, endoscopic mucosal resection followed by radiofrequency ablation is the preferred treatment. Endoscopic mucosal resection is a procedure designed to remove mucosa and superficial submucosal tissue and serves as both a diagnostic and a therapeutic procedure.

If there are advanced features such as nodularity, ulcers, or strictures seen in the segment of Barrett’s esophagus, endoscopic mucosal resection of these lesions should be performed first and treatment based upon histological assessment. These more advanced endoscopic features have been shown to be associated with an increased risk of esophageal adenocarcinoma.⁴ Patients with stage T1b (tumor with extension to submucosa) or more advanced esophageal adenocarcinoma should be managed by a multidisciplinary team consisting of oncology, surgical oncology, and advanced endoscopy. These patients likely need adjuvant chemoradiation and consideration of esophagectomy.

In patients who are treated endoscopically and have complete elimination of intestinal metaplasia, subsequent surveillance is based on the severity of the initial disease. In patients with low-grade dysplasia, surveillance endoscopy is performed every six months in the first year and then annually thereafter. In patients with high grade dysplasia or stage T1a esophageal adenocarcinoma surveillance endoscopy is done every three months for the first year, every 6 months in the second year, and then yearly thereafter. For recurrent disease, treatment follows the same histological algorithm that was used before treatment.

Future Technologies

Conventional endoscopy is still considered the gold standard for diagnosing BE. However, current surveillance programs are expensive and time-consuming, creating the need for less invasive and more cost effective screening methods.⁶

Newer technologies such as unsedated transnasal endoscopy,⁸ capsule endoscopy, chromoendoscopy, biomarkers, and Cytosponge (esophageal samples are obtained using a sponge at the end of a wire), and risk prediction models will likely become more prevalent and useful as diagnostic and risk stratification tools in the future.

Summary

Barrett’s esophagus is a risk factor for EAC. Unfortunately, EAC has a poor prognosis if diagnosed late. Understanding the screening and surveillance practices will help identify patients at increased risk for EAC. Best practices will likely continue to evolve as increased emphasis on risk stratification helps to target those who are most likely to progress to EAC. An ever-expanding armamentarium of therapeutics is now available to help tackle the progression of Barrett’s to EAC.

Biography

Daniel E. Bujanda, MD, (left), is a Fellow and Christine Hachem, MD, (right), is an Associate Professor of Internal Medicine in the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, Mo.

Contact: Christine.Hachem@health.slu.edu