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GERD 2004: issues from the past and a consensus for the future.

Abstract

In the early 1900's, gastroesophageal reflux disease (GERD) was an almost unknown entity with less than 200 cases reported worldwide. Currently the disease is regarded as almost endemic with as much as 25% of the population in some countries exhibiting signs or symptoms of reflux. Early therapies directed at chemical neutralization (milk drip, antacids) were of modest effect and required constant administration for efficacy. The introduction of histamine 2 receptor antagonists in the 1970's dramatically improved the management of GERD, but was limited by problems of tachyphylaxis and adverse events. The advent of the PPI class of drugs revolutionized medical care of GERD, given their efficacy and safety profile. As a consequence, the surgical approach with its pronounced dependence on individual operator skill and its high morbidity and even mortality has fallen into disregard. Thus, modest surgical outcome results as compared to the efficacy of PPIs has led to the widespread recognition that pharmacological therapy for GERD represents the platinum standard of care and the current consensus is that the PPI class of drugs provide the safest and most effective form of therapy for GERD. Furthermore, it is apparent based on acid suppression, symptom relief and healing rates, that all PPIs are on a milligram for milligram basis similarly efficacious for the management of GERD. While a consensus exists in regard to the current management of GERD with PPIs there is little agreement as to the management of the associated mucosal metaplastic process. At this time there is inadequate understanding of the biological basis of the mucosal transformation and minimal information about the mechanistic regulation of this event and its perpetuation. A future consensus thus requires the identification of the appropriate tools to detect Barrett's early, identify the specific molecular markers associated with neoplastic transformation and establish a definitive therapeutic algorithm.

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BibTeXRIS

Irvin Modlin, Mark Kidd. 2004. GERD 2004: issues from the past and a consensus for the future.. https://doi.org/10.1016/j.bpg.2004.06.013

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Expression of the Na+/I- symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus.

BACKGROUND: The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I-) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract. METHODS: Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients. RESULTS: Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps. CONCLUSION: That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease.

Barrett Esophagus↗