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Omeprazole Therapy in Resistant Reflux Disease
- Helge L. Waldum, MD; and
- Eiliv Brenna, MD
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TO THE EDITOR:
We read with interest the article by Klinkenberg-Knol and coworkers [1] on omeprazole safety and the accompanying editorial by Freston [2]. Although the report by Klinkenberg-Knol and colleagues [1] offered a well-balanced description of gastrin values and micronodular neuroendocrine cell hyperplasia in the oxyntic mucosa of many patients receiving omeprazole maintenance treatment, the editorial [2] tended to underestimate the risks for hypergastrinemia. Thus, it was not considered that the maximal functional and trophic effects of gastrin in the rat and in humans on the enterochromaffin-like (ECL) cell are reached at a concentration of less than 500 pM [3]. Therefore, greatly elevated gastrin values in patients with pernicious anemia are irrelevant. It is speculative to propose that the ECL-cell hyperplasia in patients with omeprazole-induced hypergastrinemia is the result of gastritis [4] because it is well known that hypergastrinemia itself is sufficient to provoke such changes in animals. Klinkenberg-Knol and colleagues reported that many patients retained food in the stomach, which could have contributed to the hypergastrinemia. This food retention could, however, be secondary to the omeprazole treatment [5]. Also, Larsson and colleagues from the Hassle Group have reported such a finding at high omeprazole doses in the rat.
Considering that carcinogenesis is often a process that requires decades, and that neuroendocrine cells (including ECL cells) [3] may give rise to malignant gastric tumors, it seems biased to conclude that there is a “diminishing concern about omeprazole-induced hypergastrinemia” [2]. It should be realized that ECL cell-derived tumors developed in rats after lifelong hypergastrinemia and that an observation period of a few years is far too brief to exclude serious long-term consequences in humans. The micronodular neuroendocrine cell hyperplasia reported by Klinkenberg-Knol and colleagues resembles the changes occurring in rats before the development of carcinoid tumors. Therefore, iatrogenic hypergastrinemia should be avoided, particularly in younger persons.
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
