Partial Fundectomy Results in Hypergastrinaemia and the Development of Gastric ECL Cell Carcinoids in the Rat

Havu, Niilo; Mattsson, Hillevi; Carlsson, Kerstin; Lundell, Lars; Carlsson, Enar; Bräutigam, John

doi:10.3109/00365528909091272

Cited by 7 publications

(1 citation statement)

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“…Although there are concerns of hypergastrinemia with acid suppression therapy, endogenous levels of gastrin increase as the result of a number of factors, including surgical procedures, such as partial fundectomy in animal models (21,22) and in older patients (23), those infected with H. pylori (23), and in patients with shortbowel syndrome, renal failure, or gastric distention (17). Moreover, although concerns have been raised regarding the effect of hypergastrinemia on enterochromaffin-like (ECL) cells' and gastric parietal cells (16,19,24), the changes that occur in the endocrine cells of the stomach for up to 5 years are generally considered to be minimal, self-limiting, and without dysplastic or neoplastic features (25).…”

Section: Discussionmentioning

confidence: 99%

Safety of Lansoprazole in the Treatment of Gastroesophageal Reflux Disease in Children

Tolia,

Fitzgerald,

Hassall

et al. 2002

J. pediatr. gastroenterol. nutr.

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Objectives:To evaluate the safety of lansoprazole in children between 1 and 11 years of age.Methods:In a phase I/II, open‐label, multicenter (11 sites) study, children with symptomatic gastroesophageal reflux disease (GERD), erosive esophagitis (≥grade 2), and/or esophageal pH < 4 for > 4.2% of the 24‐hour period were assigned, on the basis of body weight, to lansoprazole 15 mg (≤30 kg) or 30 mg (>30 kg) once daily for 8 to 12 weeks. At the discretion of the investigator, the dosage of lansoprazole was increased up to 60 mg daily in children who continued to be symptomatic after 2 weeks of treatment. Safety for all study participants was monitored by adverse event reports and laboratory evaluations.Results:Sixty‐six children were enrolled in the study and were included in the safety analysis. Throughout the treatment period, no child discontinued therapy because of an adverse event and no. clinically significant changes in laboratory values were observed. Three of the 32 children (9%) who received lansoprazole 15 mg once daily (mean exposure 50.3 days) and 6 of the 34 children (18%) who received the 30 mg once‐daily dose (mean exposure 49.4 days) experienced one or more treatment‐related adverse events before any dose increase. The three children in the lansoprazole 15 mg treatment group were treated with doses of 0.6 mg to 1.2 mg/kg/day; those in the lansoprazole 30 mg treatment group were treated with doses of 0.7 mg to 0.9 mg/kg/day. Only one child experienced a new treatment‐related adverse event after an increase in lansoprazole dose to 1.3 mg/kg/day. Treatment‐related events experienced by two or more children were: constipation (lansoprazole 15 mg QD, two children; lansoprazole 30 mg QD, one child), and headache (lansoprazole 30 mg QD, two children). Mean fasting serum gastrin levels were significantly increased from 58.0 pg/mL at baseline to 112.4 pg/mL at week 2 and 121.9 pg/mL at the final visit (P ≤ 0.001 for each comparison). However, the median fasting serum gastrin levels at the week 2 and the final visit were within the normal range (25‐111 pg/mL).Conclusion:Lansoprazole, when administered on the basis of body weight in children between 1 and 11 years of age, is safe and well‐tolerated.

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Section: Discussionmentioning

confidence: 99%

Safety of Lansoprazole in the Treatment of Gastroesophageal Reflux Disease in Children

Tolia,

Fitzgerald,

Hassall

et al. 2002

J. pediatr. gastroenterol. nutr.

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Acid suppression and gastric mucosal cell biology

et al. 1994

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This review examines recent concepts of gastric mucosal cell biology in relation to acid inhibition. Powerful acid-inhibitory drugs have been associated with the production of enterochromaffin-like (ECL) cell proliferation and the induction of ECL-cell carcinoids in rats. The ECL-cell lineage and its renewal is discussed, and the factors that regulate ECL-cell proliferation are reviewed. Current methods in use for assessing genotoxicity in gastric mucosa are scrutinized; the much discussed claim that antisecretory drugs induce unscheduled DNA synthesis is examined, and the methodology that is the basis for these claims is found defective and wanting. The nature of ECL-cell proliferation in rats receiving lifelong treatment with H2-receptor antagonists or acid pump inhibitors is explored, and their relationship to ECL-cell proliferation and ECL-cell carcinoids discussed. It is concluded that aged rats are very prone to developing endocrine proliferations, and this may be related to the multiple endocrine neoplasia syndrome found in humans. There is no evidence at present that long-term antisecretory therapy causes significant ECL-cell proliferation in humans.

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