Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Barrett's Esophagus
Chapter: Screening and surveillance

What factors can predict progression and regression of Barrett's esophagus?

A.P. Weston (Kansas City)

The risk of malignant transformation of Barrett's esophagus has been reported to vary between 1 of 46 to 1 of 441 patient years. However, the vast majority of Barrett's patients do not undergo malignant progression, but die from unrelated diseases. Identification of simple, easily attainable, non-cumbersome clinical, endoscopic, histologic and molecular features that could accurately predict the development of Barrett's adenocarcinoma (i.e. risk stratification), thereby provide a guide for the timing of surveillance examinations, would be of tremendous utility in this era of medical cost containment. Likewise, understanding what features/factors of Barrett's predict complete endoscopic and histogic regression, would again provide valuable information for timing of surveillance intervals and reassurance to both the patient and health care professionals of a healthy outcome.

Barrett's progression

Factors that have been associated with esophageal adenocarcinoma and or progression of Barrett's to Barrett's adenocarcinoma include (Table I).

Barrett's regression and normalization: spontaneous

Barrett's has been rarely reported to undergo complete regression after successful antireflux surgery. Incomplete Barrett's regression with appearance of squamous islands and

Table I. Factors associated with esophageal adenocarcinoma and or progression of Barrett's to Barrett's adenocarcinoma

downward extension and broadening of squamous tongues is far more common occurrence and has been noted after antireflux surgery as well as with long-term continuous proton pump inhibitor treatment. The histogenesis of Barrett's esophagus has been shown to involve the replacement of damaged squamous epithelium by creeping extensions of cardiac-junctional type mucosa within which over time and with persistent inflammation, focal areas of intestinal metaplasia (IM) evolve. Progressively greater amounts of IM within the tubular esophagus develop. Barrett's regression is also a stepwise process, with specialized columnar epithelium being replaced by junctional epithelium concurrent with decreased gastric mucosa surface area within the tubular esophagus. Over prolonged periods of time the junctional epithelium is replaced by squamous tissue. Evidence for this step-wise, progressive endoscopic and histologic regression was initially reported by our center in 1997. In 50% (13 of 26) of Barrett's esophagus patients with 2 cm or less of specialized epithelium complete absence of goblet cells was noted (only junctional epithelium) during prospective follow up averaging 18.6 months. These findings have also been confirmed and expanded upon by the RK Wong and his Walter Reed Army Medical Center group with their findings updated at DDW 2000. The incidence of mucosal normalization (defined here as loss of specialized columnar epithelium) as well as decrease in Barrett's esophagus length was examined in a cohort of 71 patients, 30 with esophagogastric junction-specialized intestinal metaplasia (EGJ-SIM), 31 with short segment Barrett's esophagus (SSBE) and 10 with long segment Barrett's esophagus (LSBE). A significantly greater loss of specialized epithelium was noted for EGJ-SIM 21/30 or 70% versus SSBE 12/31 or 39% versus LSBE 1/10 or 10% (p = 0.04). Multivariate analysis showed that this normalization was significantly associated with shorter Barrett's lengths, lack of hiatal hernia (HH), and female gender.

Complete spontaneous Barrett's regression has recently been examined prospectively by Weston et al. in which 99 patients with Barrett's esophagus were followed for a minimum of 2 years (mean of 48.0 months). Overall, 7 (7.1%) of Barrett's patients had complete regression of their Barrett's esophagus. Univariate and stepwise logistic regression analysis showed that complete regression was associated with absence of HH. Re-examination of the multivariate analysis by examining only HH (present yes versus no) and length of Barrett's ( < 6 cm versus > 6 cm) revealed that both HH (p = 0.0447) and length of Barrett's (p = 0.0418) were predictive of complete regression. The observed probability of complete regression was inversely related to increasing HH size: 0% probability in patients with large HH (size > 6 cm), 4.3% for small and medium sized (between 1 cm and 5 cm) and 10% with no HH.


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8. Younes M, Ertan A, Lechago LV, et al. p53 protein accumulation is a specific marker of malignant potential in Barrett's metaoplasia. Dig Dis Sci 1997;42:697-701.

9. Weston AP, Banerjee SK, Persons DL, et al. p53 positivity in low-grade dysplasia (LGD) in Barrett's esophagus: marker predictive of progression to cancer or multifocal high-grade dysplasia. Am J Gastroenterol 1999;94(9):2603.

10. Horwhat JD, Baroni D, Maydonovitch C, et al. The incidence of regression and normalization of intestinal metaplasia in a cohort of patients with EGJ-SIM, SSBE and LSBE followed over 3 years. Gastroenterology 2000;118:A224.

Publication date: August 2003 OESO©2015