Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: Barrett's Esophagus
Chapter: Screening and surveillance

After endoscopic therapy, how to evaluate the potential risk of dysplastic and neoplastic changes in columnar epithelium remaining beneath regenerated squamous mucosa?

H.S. Garewal (Tuckson)

Ablation therapy, i.e. attempts at eradicating Barrett's esophagus, is becoming increasingly popular since the fundamental approach was hypothesized several years ago. At the last symposium, I discussed the pluripotent nature of the esophageal stem cell and illustrated this by pointing out the changes that the esophageal lining goes through in utero. We also postulated that once intestinal metaplasia (IM) is established, by reflux, it is a stable lesion that does not go away simply by decreasing reflux. This is corroborated by the number of negative studies using long-term acid suppression, even with proton pump inhibitors (PPIs), or antireflux surgery. The most one sees is the appearance of so-called squamous islands, i.e. areas in which squamous epithelium appears. Currently, the approaches used for ablation combine a method for injuring the epithelium in an acid or reflux-suppressed environment. The methods differ only in the technique of re-injury, which has included photodynamic therapy, use of lasers or multipolar electrocoagulation (MPEC). With this approach, a high percentage of patients will undergo reversal of their IM back toward squamous epithelium. Nevertheless, in a significant number of cases, the reversal is incomplete with areas of IM persisting either alongside or below the squamous epithelium.

The obvious question regarding ablation is whether we are actually reducing the risk of cancer by exposing an individual to these techniques. The best approach to answering this question would clearly be a prospective trial in which the risk of cancer is assessed over time. Nevertheless, such a study is practically and logistically impossible given the number of patients that would be needed. Thus, our approach has been to study biomarkers in the reversed epithelium to assess whether they are normally or abnormally expressed.

Our initial findings suggest that complete reversal (i.e. only squamous epithelium is present and no residual IM) results in squamous epithelium that is indistinguishable from normal squamous epithelium. We have found that expression of p53 as well as proliferation characteristics of this epithelium are identical to normal tissue. Consequently, we postulate that this squamous epithelium will be a low risk situation. On the contrary, in the partial reversal setting, we have noticed abnormal expression of biomarkers, especially at the junction of persistent or recurrent IM and new or neo-squamous epithelium. The proliferation is increased and, in the squamous regions, occurs in multiple layers rather than the basal layer only. Similarly, proliferation in the glands on the IM side is also markedly increased. P53 expression was found to be abnormal in a number of cases, thereby raising the possibility that cancer risk may indeed be increased in this setting [1]. This is an area that needs further study fairly urgently, since ablation is becoming evermore popular for these patients. Incomplete ablation can occur in up to 30-40% of patients when carefully assessed at 6-12 months after completion of the ablation procedure. Given the difficulties with a clinical trial, use of a wide range of biomarkers needs to be assessed to guide us on this issue.


1. Garewal H, Ramsey L, Sharma P, Kraus K, Sampliner R, Fass R. Biomarker studies in reversed Barrett's esopagus. Am J Gastroenterol 1999;94:2829-2833.

Publication date: August 2003 OESO©2015