Chandrasoma P, Wickramasinghe K, Ma Y, DeMeester T. Is intestinal metaplasia a necessary precursor lesion for adenocarcinoma of the distal esophagus, gastroesophageal junction and gastric cardia? Dis Esoph 2007;20(1):36-41

The Departments of Surgical Pathology and Foregut Surgery, Keck School of Medicine and University of Southern California, Los Angeles, California, USA.
Diseases of the Esophagus (Impact Factor: 1.78). 02/2007; 20(1):36-41. DOI: 10.1111/j.1442-2050.2007.00638.x
Source: PubMed


Adenocarcinoma of the distal esophagus and gastroesophageal junction are believed to arise in Barrett's esophagus with intestinal metaplasia. Whether adenocarcinoma can arise in columnar lined esophagus without intestinal metaplasia is in doubt. Whether adenocarcinoma of the gastric cardia arises in intestinal metaplasia of the gastric cardia is also in doubt. We aim to evaluate the relationship of size and stage of adenocarcinoma of the distal esophagus, gastroesophageal junction and gastric cardia to intestinal metaplasia and other types of columnar epithelium. Seventy-four patients who had esophagogastrectomy for adenocarcinomas in this region were examined histologically to assess the frequency of residual intestinal metaplasia in the surrounding epithelium. Tumors without residual intestinal metaplasia were evaluated for the presence of other columnar epithelia and correlated with tumor size and stage. Cardiac mucosa was present around all tumors. Residual intestinal metaplasia was present in 48 (65%) tumors, including 33/38 (87%) distal esophageal, 10/25 (45%) junctional and 5/11 (45%) gastric cardia tumors. The prevalence of intestinal metaplasia was 100% in all tumors that were less than 1 cm in maximum diameter and all intramucosal tumors. The prevalence of residual intestinal metaplasia decreased with increasing tumor size and stage. These data strongly support the contention that adenocarcinomas of this region, including those in the gastric cardia, arise in intestinal metaplastic epithelium. The absence of residual intestinal metaplasia in larger tumors is the result of tumor overgrowing the intestinal metaplasia from which it arose.

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Available from: Parakrama T Chandrasoma, Jul 10, 2014
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    • "The most common are several nonintestinal and the specialized intestinal type of columnar metaplasia; the latter is also referred to as intestinal metaplasia (IM). IM is associated with a higher risk of developing esophageal adenocarcinoma (EAC) (Chandrasoma et al., 2007). BE develops in 15%–20% of patients suffering from chronic gastroesophageal reflux disease (Spechler et al., 2010). "
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    ABSTRACT: The molecular mechanisms leading to epithelial metaplasias are poorly understood. Barrett's esophagus is a premalignant metaplastic change of the esophageal epithelium into columnar epithelium, occurring in patients suffering from gastroesophageal reflux disease. Mechanisms behind the development of the intestinal subtype, which is associated with the highest cancer risk, are unclear. In humans, it has been suggested that a nonspecialized columnar metaplasia precedes the development of intestinal metaplasia. Here, we propose that a complex made up of at least two factors needs to be activated simultaneously to drive the expression of intestinal type of genes. Using unique animal models and robust in vitro assays, we show that the nonspecialized columnar metaplasia is a precursor of intestinal metaplasia and that pSMAD/CDX2 interaction is essential for the switch toward an intestinal phenotype.
    Preview · Article · Apr 2014 · Cell Reports
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    Full-text · Article · Sep 2009 · Human pathology
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    • "It is well known that stress exposure [55] [58] may also lead to changes in the motility and in the function of the LES. As lowranking NHPs housed in a group setting usually have a much lower access to food than high-ranking NHPs [40], it is not unconceivable that low-ranking NHP might have been subjected to daily stress. iv) Is the chemical component of the refluxate bathing the mucosal microenvironment responsible for the development of columnar-lined esophagus? "
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    ABSTRACT: Despite that anatomists consider the cardia as a portion of the stomach, there is disagreement in the literature over whether the cardia mucosa, described as columnar-lined with mucus-producing glands (CLMMG) with or without occasional interspersed oxyntic cells, is part of the stomach, part of the esophagus or a distinct entity. For some authors this mucosa phenotype is a metaplastic glandular change of the distal esophagus caused by protracted gastro-esophageal reflux (GER). In this survey, the presence of CLMMG mucosa was searched for at the esophagus-gastric junction in 50 non-human primates (NHP). The length of the CLMMG (between the squamous epithelium of the esophagus and the first oxyntic fundic gastric gland) was assessed by the aid of an ocular microscale. In all three foetuses, all four stillborn baboons and one 4 day old baboon, the columnar-lined mucosa showed depressions that corresponded to early epithelial pits without glands. In the remaining 45 post-natal NHP, the length of the CLMMG mucosa varied from 0.8 mm to 25.2 mm, and the CLMMG mucosa had replaced the distal esophageal squamous epithelium. The size was neither influenced by the post-natal age nor by the gender of the animals. In NHP, regurgitation with rumination is a natural physiological process leading to GER. The present investigation substantiates the notion that the columnar-lined mucosa with mucus-producing glands is a post-natal developmental process in NHP. These animals seem to offer an excellent spontaneous model to study the series of histological events that take place in the distal esophagus of NHP, most likely under the influence of protracted GER.
    Full-text · Article · Feb 2009 · International journal of clinical and experimental pathology
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