By Mahmoud Barrie, M.D.
From ATLANTA Medicine, 2012, Gastroenterology, Vol. 82, No. 4
Barrettâ€™s esophagus continues to be an evolving condition due to continued improvements in the areas of definition, pathophysiology, surveillance, diagnosis and therapeutic options.
The definition of Barrettâ€™s esophagus in the United States has remained relatively unchanged as â€œsalmon colored mucosa at the distal esophagus on endoscopy and evidence of intestinal metaplasia in the squamocolumnar junction on histology.â€ However, the British Society of Gastroenterology (BSG) defines Barrettâ€™s esophagus as â€œan endoscopically apparent area above the esophagogastric junction that is suggestive of Barrett esophagus [salmon-colored mucosa], which is supported by the finding of columnar lined esophagus on histology,â€ suggesting that the presence of intestinal metaplasia is not a requirement. The BSG definition takes into account the absence of intestinal metaplasia due to sampling errors and the development of cancer in the absence of intestinal metaplasia. This definition, however, potentially increases the number of patients with the disease.
The mechanism of metaplasia in Barrettâ€™s esophagus has not been well established. Mucosal injury from acid reflux is believed to be a prerequisite to its development, however, other factors â€” such as increased mucosal permeability â€” must be involved because not all patients with acid reflux develop Barrettâ€™s esophagus.
Furthermore, a study by Fletcher et al. has revealed the formation of a pocket of highly acidic area at the gastroesophageal junction, which converts dietary nitrates to mutagenic Nitric oxide within the pocket, as a potential pathway to developing Barrettâ€™s esophagus with dysplasia.
Surveillance and Risk Assessment
Despite the development of the Prague C and M (C=circumference and M=maximal length of Barrettâ€™s, including tongues) classification of Barrettâ€™s esophagus, only Prague M is used with any degree of consistency. A Barrettâ€™s esophagus > 3 cm in length has been shown to increase the risk of development of dysplasia or adenocarcinoma.
Additionally, the question of who needs surveillance continues to evolve. White males older than age 50 with long-term dyspepsia were thought to be highest risk group. However, the new American Gastroenterological Association (AGA) guidelines suggest screening for Barrettâ€™s esophagus in patients with multiple risk factors (such as being white, male and age 50 or older, and having elevated body mass index, diabetes, truncal obesity, chronic dyspepsia and/or hiatal hernia). There is no suggestion of the minimal number of risk factors required, but it is implied that screening is no longer limited to 50-year-old Caucasian males with chronic dyspepsia. The number of biopsies and the timing of surveillance endoscopy also have changed, perhaps to reflect the low incidence of adenocarcinoma (0.2% to 3.5% per year) and the cost of surveillance.
Most experts, including the AGA, recommend taking four quadrant biopsies every 2 cm in nondysplastic Barrettâ€™s esophagus patients, but every 1 cm Barrettâ€™s esophagus continues to be an evolving condition due to continued improvements in patients with known or suspected dysplasia. The endoscopic surveillance interval has been increased to every three to five years for nondysplastic Barrettâ€™s esophagus patients and every six to 12 months for patients suspected of having dysplasia. For high-grade dysplasia without option of eradication, surveillance endoscopy every three months is recommended.
New Diagnostic Tools
Diagnosis of Barrettâ€™s esophagus relies heavily on biopsy samples obtained from endoscopy. Thus, the ability to endoscopically identify Barrettâ€™s esophagus with or without dysplasia will determine accuracy of the biopsies and, ultimately, the benefits of surveillance. New developments in enhanced imaging techniques â€” such as narrow band imaging (NBI), chemoendoscopy, confocal laser microscopy (CLM) and autofluorescence imaging (AFI) â€” are proving to be great assets.
NBI produces high-resolution images of the mucosa to help identify pre-malignant or malignant areas on the basis of irregular mucosal pattern. While CLM provides information at the cellular level during ongoing endoscopy, AFI uses blue light to detect fluorescence from biological tissue. However, the AGA guidelines do not currently support these techniques in the routine diagnosis of Barrettâ€™s esophagus.
The cornerstone for the treatment of Barrettâ€™s esophagus is acid reflux therapy because mucosal injury from acid reflux is believed to be a prerequisite for the development of Barrettâ€™s esophagus. It is important, however, to recognize that there are no prospective trials confirming that control of acid reflux prevents Barrettâ€™s esophagus or cancer.
Multiple endoscopic techniques have developed for the management of Barrettâ€™s esophagus with or without dysplasia. These include thermal techniques (multipolar electrocoagulation, argon plasma coagulation, heater probe, laser and radiofrequency ablation [RFA], and neodymium-doped ytrium aluminium garnet [ND:YAG]) and nonthermal techniques (photodynamic therapy, endoscopic mucosal resection [EMR] and cryotherapy). In a multicenter, randomized, sham-control trial by Shaheen et al, RFA was shown to produce complete eradication in 81% of patients with high-grade dysplasia and an overall complete eradication of intestinal metaplasia in 77.4% of patients â€” compared to 19% and 2.3%, respectively, in the control group.
Furthermore, eradication was observed in 90.5% of patient with low-grade dysplasia as compared to 22.7% in the control group. The risk for disease progression was also shown to be statistically lower in the RFA group compared to control. Therefore, RFA has emerged as the standard of care for flat lesions associated with Barrettâ€™s esophagus with dysplasia and EMR is advocated for raised nodules.
Barrettâ€™s esophagus is an evolving field with recent developments that are aimed at improving its diagnosis, surveillance and therapy. The incorporation of these new developments into daily practice will be gradual and deliberate with the ultimate goal of preventing esophageal adenocarcinoma due to Barrettâ€™s esophagus.
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