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.
BACKGROUND
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.


OBJECTIVE
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.


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


METHODS
Assessment of MEN1, gastric hypersecretion, and gastroscopy with multiple biopsies was done according to a fixed protocol and tumor status. ECL-cell changes and alpha-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 alpha-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.
Berna
Marc J
MJ
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1804, USA.
Annibale
Bruno
B
Marignani
Massimo
M
Luong
Tu Vinh
TV
Corleto
Vito
V
Pace
Andrea
A
Ito
Tetsuhide
T
Liewehr
David
D
Venzon
David J
DJ
Delle Fave
Gianfranco
G
Bordi
Cesare
C
Jensen
Robert T
RT
D000293:Adolescent; D000328:Adult; D000368:Aged; D002276:Carcinoid Tumor / Q000097:blood / Q000209:etiology* / Q000473:pathology; D019861:Enterochromaffin-like Cells / Q000473:pathology*; D005260:Female; D005755:Gastrins / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000473:pathology*; D011446:Prospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood / Q000209:etiology* / Q000473:pathology; D015043:Zollinger-Ellison Syndrome / Q000473:pathology*
D005755:Gastrins