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Diseases & Conditions

Barretts Esophagus - Digestive Disease Overview

Barrett's esophagus is the most severe complication of chronic gastroesophageal reflux disease (GERD) and would be of no real importance were not for the well recognized association of Barrett's esophagus and adenocarcinoma of the esophagus. The incidence of adenocarcinoma of the esophagus due to Barrett's Esophagus and GERD is on the rise and the five year survival rate for this cancer remains dismal.

However, cancer risk for a given patient with Barrett’s esophagus is lower than previously estimated. Current strategies for improved survival in patients with esophageal adenocarcinoma focus on cancer detection at an early and potentially curable stage. This can be accomplished either by screening more patients for Barrett's Esophagus or with endoscopic surveillance of patients with known Barrett’s esophagus.

Cleveland Clinic has a multidisciplinary clinical care and translational research program dedicated to a comprehensive scientific approach to the management of GERD, Barrett's Esophagus and early esophageal adenocarcinoma.

The components of this program include the following core areas:

  • Cancer Biology
  • Anatomic Pathology
  • Molecular Pathology
  • Cytopathology
  • Thoracic Surgery
  • Gastroenterology
    • Endoscopy – Imaging and Intervention
    • Pharmacologic Treatment
  • Epidemiology and Biostatistics
    • Barrett’s Esophagus Registry
  • Ohio Familial Barretts Esophagus Consortium
  • Medical Oncology

For patients with Barrett’s esophagus, Cleveland Clinic offers the following:

  • Expertise in diagnosis and treatment
  • Expertise in pathologic diagnosis
  • Entry into a Registry to remind patients of their next follow-up surveillance date
  • Opportunities to participate in clinical research programs examining:
    • Novel endoscopic imaging
    • New approaches to medical therapy and chemoprevention
  • Entry into the Ohio Familial Barrett's Esophagus Consortium Research Program

For patients with Barrett’s esophagus and dysplasia or early cancer:

  • Expertise in diagnosis and treatment
  • Expertise in pathologic diagnosis
  • Expertise in esophageal surgery
  • Expertise in endoscopic intervention
  • A multidisciplinary approach involving gastroenterologists, pathologists, thoracic surgeons and oncologists
  • Opportunities to participate in clinical research programs examining novel endoscopic imaging techniques and cancer risk
  • New approaches to medical therapy and chemoprevention

In theory, the diagnosis of Barrett’s esophagus should be fairly simple; namely the presence of intestinal metaplasia anywhere in the tubular esophagus. The evolving concept of short segment Barrett’s esophagus makes the diagnosis of Barrett’s esophagus a bit more problematic.

The difficulty in diagnosing short segment Barrett’s esophagus is because the precise junction of the stomach and the esophagus may be difficult to determine endoscopically due to the presence of a hiatal hernia, inflammation, and disassociation between the squamocolumnar junction and the lower esophageal sphincter zone in normal individuals. As such, an irregular Z-line may appear abnormal to one observer and normal to another one.

Biopsies from a normal gastroesophageal junction may also reveal intestinal metaplasia which is presumed to represent intestinal metaplasia of the cardia. These differences are not merely semantics. The dysplasia risk in short segment Barrett’s esophagus is significantly greater than in intestinal metaplasia of the cardia. As such, surveillance is recommended for patients with short segment Barrett’s esophagus but not for patients with intestinal metaplasia of the cardia.

Despite the widespread emphasis on the importance of specialized columnar epithelium as the sine qua none of Barrett’s esophagus and increased cancer risk, many pathologists continue to classify gastric metaplasia without intestinal metaplasia as Barrett’s esophagus thereby increasing patient alarm and needlessly subjecting many individuals to unnecessary surveillance endoscopy.

Techniques such as methylene blue staining may be helpful in directing biopsies, especially in patients with suspected short-segment Barrett’s esophagus, since the stain is typically picked up by specialized columnar epithelium. Another possible option is to examine the immunohistochemical cytokeratin staining patterns of biopsies obtained from questionable areas of Barrett’s esophagus. Recent work suggests that characteristic staining patterns may reliably distinguish between intestinal metaplasia of the stomach and the esophagus.

Therefore, at the time of endoscopy, landmarks should be carefully defined: the diaphragmatic hiatus, esophagogastric junction, and squamocolumnar junction. If the squamocolumnar junction is above the level of the esophagogastric junction, biopsies should be obtained. If intestinal metaplasia is present, defined by goblet cells seen with combined hematoxylin and eosin-alcian blue pH 2.5 stains, the patient is considered to have Barrett’s esophagus and should be placed in a surveillance program.

Biopsies of the squamocolumnar junction should not be routinely obtained in clinical practice if it is at the level of the gastroesophageal junction. Goblet cells found at this level should be considered to be diagnostic of intestinal metaplasia of the gastric cardia, a condition with an unclear cancer risk and one in which cancer surveillance is not yet recommended.

These patients may well be infected with H. pylori, a diagnosis that can be confirmed with biopsies of the more distal antrum and fundus or noninvasive techniques such as the urea breath test, stool antigen studies or serology.

Proton Pump Inhibitors

Acid suppression with proton pump inhibitors is the cornerstone of medical therapy for Barrett’s esophagus. Studies show these inhibitors result in consistent symptom relief. However, even at high doses, the result in either no regression of the Barrett’s segment or modest clinically insignificant regression. Proton pump inhibitors typically increase squamous islands in the Barrett’s segment, but biopsies taken from such islands typically show underlying intestinal metaplasia.

It is clear that symptom control with proton pump inhibitor therapy is not necessarily equivalent to normalization of esophageal acid exposure, even with the use of high doses. The mechanism underlying the failure of acid suppression in Barrett’s esophagus patients remains unknown. While there are no data to suggest that normalization of esophageal acid exposure decreases cancer risk in these patients, recent studies show that short-term normalization of intraesophageal acid exposure in Barrett’s esophagus patients decreases cellular proliferation and increases cellular differentiation. The implication of this finding is that adequate control of esophageal acid exposure could theoretically decrease the risk of cancer by decreasing cell proliferation rates. However, this remains unproven to date. Currently, it is unclear if Barrett’s patients should undergo routine 24-hour pH monitoring to assess the response to therapy. Clearly, the costs of such an approach would be substantial and patient acceptance of this would be problematic. Furthermore, the ability to act on this information in patients already receiving high doses of proton pump inhibitors is uncertain. Still other patients with Barrett’s esophagus are completely asymptomatic without any antisecretory therapy. It is unclear if these patients should be offered antisecretory therapy at all.

Antireflux Surgery

Antireflux surgery also effectively alleviates GERD symptoms in Barrett’s patients. However, regression of Barrett’s epithelium is uncommon. Some surgical enthusiasts suggest that antireflux surgery decreases the subsequent risk of developing esophageal cancer, by decreasing both acid and duodenogastric reflux. However, there are few studies that support this concept. Thus, while surgery provides an excellent means of symptom control in Barrett’s patients, it probably does not influence the natural history of Barrett’s esophagus. Furthermore, antireflux surgery is not necessarily a permanent solution as breakdown of the operation remains a problem even in the best of surgical hands.

Ablation Therapy

Ablation therapy of Barrett’s esophagus without dysplasia is achievable by a number of different techniques. However, ablation should be viewed as experimental only, and not offered to patients as part of routine clinical practice. It is unknown if this therapy reduces the already small risk of esophageal adenocarcinoma in Barrett’s esophagus. All ablation therapy techniques typically result in residual macroscopically invisible intestinal metaplasia beneath the neosquamous lining that can still result in subsequent cancer.

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