50-Year Appraisal of Gastrinoma: Recommendations for Staging and Treatment E Christopher Ellison, MD, FACS, Joann Sparks, BS, Joseph S Verducci, PhD, Jerome A Johnson, PhD, Peter Muscarella, MD, FACS, Mark Bloomston, MD, W Scott Melvin, MD, FACS BACKGROUND: Gastrinoma is a rare neuroendocrine tumor associated with ulcerogenic syndrome. The purpose of this study was to provide information on current controversies related to treatment, including staging, patient selection, and outcomes for surgical resection. STUDY DESIGN: A retrospective review of 106 patients with gastrinoma. Patients were classified as sporadic gastrinoma (SG) or MEN. End points of analysis included disease-free and disease-specific survival. Kaplan-Meier survival analysis was performed and significance (p  0.05) was deter- mined by Mantel-Haenszel log-rank test. RESULTS: Gastrinoma can be staged by TNM criteria into four groups (stage 0, I, II, and III), which had notably different survival curves, dependent on tumor size and distant metastases (p  0.0001), but independent of lymph node metastases (p = 0.324). Surgical resection was possible in 72 patients (SG, n = 50; MEN, n = 22). Durable cure rate for SG was 26%, compared with 4% for MEN-1. Surgical resection achieving gross removal of all tumor resulted in improved survival in both SG and MEN patients (p  0.0001). Improved survival was independent of a normal postoperative serum gastrin. Stage III was highly predictive of incomplete resection and the associated failure to improve survival (p = 0.0001). CONCLUSIONS: Staging provides a reliable method for the clinician to select patients for operation and to provide a prognosis, and should permit better comparisons of treatment between institutions. In the management of gastrinoma, it is recommended that SG and MEN patients with clinical stage I and II disease have surgical exploration, patients with stage III disease not have manda- tory surgical treatment, and some stage 0 patients might not need routine surgical exploration. (J Am Coll Surg 2006;202:897–905. © 2006 by the American College of Surgeons) Gastrinoma is a rare neuroendocrine tumor that is asso- ciated with ulcerogenic syndrome (Zollinger-Ellison syndrome). 1,2 Since the first description in 1955, great progress has been made in treatment of this disease. 3,4 There does remain debate concerning staging, impact of resection on survival, and the role of surgical resection of gastrinoma in patients with associated MEN. 5,6 Because the disease is rare, heterogeneous, and indolent, study of these issues is challenged by low numbers of patients, making randomization impractical. Also, extended fol- lowup is needed to assess for late recurrence and to achieve survival end points. We sought answers to these controversies by analyzing a group of 106 patients seen at a single institution over the past 50 years. METHODS Patients and definition of terms A retrospective review of all patients with gastrinoma at The Ohio State University Medical Center was per- formed. The Institutional Review Board approved the study. Only patients with a minimum 5-year followup were included. Patients were categorized as sporadic gas- trinoma (SG) (nonfamilial) or gastrinoma associated with MEN. Methods to diagnose SG and MEN have been described previously. 5 No patients were lost to fol- lowup. At followup, testing included measurement of a fasting gastrin. Secretin provocative testing was per- formed as indicated by symptoms and fasting hypergas- Competing Interests Declared: None. Presented at the American College of Surgeons 91 st Annual Clinical Con- gress, San Francisco, CA, October 2005. Received October 13, 2005; Revised January 27, 2006; Accepted February 8, 2006. From the Departments of Surgery (Ellison, Sparks, Johnson, Muscarella, Bloomston, Melvin) and Statistics (Verducci), The Ohio State University, Columbus, OH. Correspondence address: E Christopher Ellison, MD, Department of Sur- gery, The Ohio State University, 327 Means Hall, 1654 Upham Dr, Colum- bus, OH 43210-1250. 897 © 2006 by the American College of Surgeons ISSN 1072-7515/06/$32.00 Published by Elsevier Inc. doi:10.1016/j.jamcollsurg.2006.02.013