title: 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.
abstract: 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.
authors.affiliation: Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1804, USA.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Berna
authors.forename: Bruno
authors.initials: B
authors.lastname: Annibale
authors.forename: Massimo
authors.initials: M
authors.lastname: Marignani
authors.forename: Tu Vinh
authors.initials: TV
authors.lastname: Luong
authors.forename: Vito
authors.initials: V
authors.lastname: Corleto
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.forename: Tetsuhide
authors.initials: T
authors.lastname: Ito
authors.forename: David
authors.initials: D
authors.lastname: Liewehr
authors.forename: David J
authors.initials: DJ
authors.lastname: Venzon
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Delle Fave
authors.forename: Cesare
authors.initials: C
authors.lastname: Bordi
authors.forename: Robert T
authors.initials: RT
authors.lastname: Jensen
mesh_terms: 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*
chemical_list: D005755:Gastrins