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Mechanism of Acid Hypersecretion Post Curative Gastrinoma Resection

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Abstract

Background

Some patients with Zollinger-Ellison syndrome post curative gastrinoma resection continue to show gastric acid hypersecretion; however, the mechanism is unknown.

Aim

The aim of this study was to prospectively study acid secretion following curative gastrinoma resection and analyze factors contributing in patients with Zollinger-Ellison syndrome.

Methods

Fifty patients cured post gastrinoma resection were studied with serial assessments of acid secretory status, cure status and ECL-cell status/activity (with serial biopsies, CgA, urinary N-MIAA). Correlative analysis was performed to determine predictive factors.

Results

Hypersecretion occurred in 31 patients (62%) and 14 had extreme-hypersecretion. There was an initial decline (3–6 months) in BAO/MAO, which then remained stable for eight years. Preoperative BAO correlated with the postoperative secretion, but not other clinical, tumoral, laboratory variables, the degree of postoperative acid suppression or type of antisecretory drug needed. Hypersecretors had greater postoperative ECL changes (P = 0.005), serum CGA (P = 0.009) and 24-h urinary N-MIAA (P = 0.0038).

Conclusions

Post curative resection, gastric hypersecretion persists long term (mean 8 years) in 62% of patients and in 28% it is extreme, despite normogastrinemia. No preoperative variable except BAO correlates with postresection hypersecretion. The persistent increased ECL-cell extent post curative resection suggests prolonged hypergastrinemia can lead to changes in ECL-cells that are either irreversible in humans or sustained by unknown mechanisms not involving fasting hypergastrinemia and which can result in hypersecretion, in a proportion of which it can be extreme. Whether similar findings may occur in patients with idiopathic GERD treated for prolonged periods (>10 years) with PPIs, at present, is unknown.

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Abbreviations

ZES:

Zollinger-Ellison syndrome

BAO:

Basal acid output

MAO:

Maximal acid output

ECL:

Enterochromaffin-like cell

CgA:

Chromogranin A

N-MIAA:

N-methyl imidazole acetic acid

PPI:

Proton pump inhibitor

GERD:

Gastroesophageal reflux disease

MEN1:

Multiple endocrine neoplasia-type 1

SRS:

Somatostatin receptor scintigraphy

PET:

Pancreatic endocrine tumor

DH:

Diffuse ECL-cell hyperplasia

LH:

Linear ECL-cell hyperplasia

MH:

Micronodular ECL-cell hyperplasia

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Acknowledgments

This study was partially supported by intramural funds of NIDDK, NIH and by grants from the Italian Association for Cancer Research (AIRC), Milan; the Italian Ministry for University, Scientific and Technological Research (MURST); the Italian Ministry of Health (grant number ICS060.2/RF00-57).

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Authors and Affiliations

  1. Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 10, Rm. 9C-103, 10 CENTER DR MSC 1804, Bethesda, MD, 20892-1804, USA

    Jeremiah V. Ojeaburu & Robert T. Jensen

  2. Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan

    Tetsuhide Ito

  3. Department of Pathology and Laboratory Medicine, Section of Pathological Anatomy, University of Parma, Parma, Italy

    Pellegrino Crafa & Cesare Bordi

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  1. Jeremiah V. Ojeaburu
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  2. Tetsuhide Ito
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Correspondence to Robert T. Jensen.

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Ojeaburu, J.V., Ito, T., Crafa, P. et al. Mechanism of Acid Hypersecretion Post Curative Gastrinoma Resection. Dig Dis Sci 56, 139–154 (2011). https://doi.org/10.1007/s10620-010-1234-1

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