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A Prospective Study of Gastric Carcinoids and Enterochromaffin-Like Cell Changes in Multiple Endocrine Neoplasia Type 1 and Zollinger-Ellison Syndrome: Identification of Risk Factors

Digestive Diseases Branch (M.J.B., R.T.J.), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Biostatistics and Data Management Section (D.L., D.J.V.), National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland 20892; Division of Digestive and Liver Diseases (B.A., M.M., V.C., G.D.F.), University "La Sapienza," 00189 Rome, Italy; Department of Pathology and Laboratory Medicine (T.V.L., C.B.), Section of Anatomic Pathology, University of Parma, 43100 Parma, Italy; Department for Internal Medicine I (M.J.B., A.P.), University Hospital Hamburg-Eppendorf, 20245 Hamburg, Germany; and Department of Medicine and Bio-Regulatory Science (T.I.), Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan

Address all correspondence and requests for reprints to: Dr. Robert T. Jensen, Building 10, Room 9C-103, 10 Center Drive, Bethesda, Maryland 20892-1804. E-mail: RobertJ{at}bdg10.niddk.nih.gov.

Context: Multiple endocrine neoplasia type 1 (MEN1) patients frequently develop Zollinger-Ellison syndrome (ZES). These patients can develop proliferative changes of gastric enterochromaffin-like (ECL) cells and gastric carcinoids (ECL-cell tumors). ECL-cell changes have been extensively studied in sporadic ZES patients and can be precursor lesions of gastric carcinoids, but little is known about factors influencing their severity or development of carcinoids in MEN1/ZES patients.

Objectives: Our objective was to prospectively analyze ECL-cell changes and gastric carcinoids (ECL-cell tumors) in a large series of MEN1/ZES patients to detect risk factors and deduct clinical guidelines.

Setting and Patients: Fifty-seven consecutive MEN1/ZES patients participated in this prospective study at two tertiary-care research centers.

Interventions and Outcome Measures: Assessment of MEN1, gastric hypersecretion, and gastroscopy with multiple biopsies was done according to a fixed protocol and tumor status. ECL-cell changes and -human chorionic gonadotropin staining were assessed in each biopsy and correlated with clinical, laboratory, and MEN1 features.

Results: ECL-cell proliferative changes were universally present, advanced changes in 53% and carcinoids in 23%. Gastric nodules are common and are frequently associated with carcinoids. Patients with high fasting serum gastrin levels, long disease duration, or a strong -human chorionic gonadotropin staining in a biopsy are at higher risk for an advanced ECL-cell lesion and/or gastric carcinoid.

Conclusions: Gastric carcinoids and/or advanced ECL-cell changes are frequent in MEN1/ZES patients, and therefore, regular surveillance gastroscopy with multiple routine biopsies and biopsies of all mucosal lesions are essential. Clinical/laboratory data and biopsy results can be used to identify a subgroup of MEN1/ZES patients with a significantly increased risk for developing gastric carcinoids, allowing development of better surveillance strategies.