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Original Investigation
March 21, 2018

Incidence and Prognosis of Primary Gastrinomas in the Hepatobiliary Tract

Author Affiliations
  • 1Department of Surgery, Stanford University, Stanford, California
  • 2Department of Surgery, Memorial Sloan Kettering Cancer Institute, New York, New York
  • 3Department of Surgery, University of Pennsylvania, Philadelphia
  • 4Department of Surgery, University of Maryland, Baltimore
  • 5Digestive Diseases Branch, National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland
JAMA Surg. 2018;153(3):e175083. doi:10.1001/jamasurg.2017.5083
Key Points

Question  Do primary gastrinomas of the liver exist?

Findings  In this series of 223 patients with Zollinger-Ellison syndrome, primary gastrinomas of the liver were the second most common extrapancreatic, extraintestinal site for a primary gastrinoma and may metastasize to regional lymph nodes. Aggressive resection is indicated because cure rates and survival are similar to those for primary gastrinomas in other locations.

Meaning  Liver primary gastrinomas occur and warrant aggressive resection including regional lymph nodes.


Importance  Zollinger-Ellison syndrome (ZES) is a life-threatening disease caused by a malignant tumor that secretes gastrin (gastrinoma). Gastrinomas typically occur in the pancreas or the duodenum.

Objective  To describe the incidence and prognosis of very unusual gastrinomas originating in the hepatobiliary tract.

Design, Setting, and Participants  This study included 223 consecutive patients at the National Institutes of Health and Stanford University Hospital who were enrolled in a prospective protocol to treat ZES using proton pump inhibitors to control acid hypersecretion and surgical resection to ameliorate the tumoral process. Data were collected from June 1982 to August 2017.

Main Outcomes and Measures  Incidence, location, surgical results, and cure rate and overall survival among patients with gastrinomas that originate in the liver or bile ducts. Cure was defined as serum gastrin levels within the reference range, negative results of a secretin test, and no tumor found on imaging.

Results  Of the 223 patients who underwent surgery to remove gastrinomas, 7 (3.1%) had liver or biliary tract primary tumors, including 5 men and 2 women (mean age at diagnosis, 43 years; range 27-54 years). The mean serum gastrin level was 817 pg/mL (range, 289-2700 pg/mL). Each patient had positive results of a secretin test. None had evidence of multiple endocrine neoplasia 1. Four patients had primary tumors in the liver (1 in segment II, 2 in segment IV, and 1 in segment V); 3, in the bile duct (1 in the right hepatic duct, 1 in the left hepatic duct, and 1 in the common hepatic duct). Surgical resection required 1 right hepatic lobectomy, 1 left lateral segmentectomy, 2 left hepatic lobectomies, 1 central hepatectomy, and 2 bile duct resections. Four patients had nodal metastases, and no patient had distant metastases. No operative deaths occurred, but 3 patients had complications, including bile duct stricture, portal vein stricture, and biliary fistula. Each patient was disease free in the immediate postoperative period, and 3 had recurrences in the liver and portal lymph nodes (at 3, 11, and 15 years). Three patients (43%) remained free of disease at follow-up ranging from 24 months to 26 years.

Conclusions and Relevance  Primary gastrinomas of the hepatobiliary tract are uncommon (3%), but the hepatobiliary system is the second most frequent extraduodenopancreatic primary location (after the lymph nodes). These tumors can occur outside the gastrinoma triangle and must be specifically considered. Furthermore, their discovery changes the operative approach because aggressive liver or bile duct resection is indicated, with high rates of long-term cure and survival and acceptable rates of complications. In addition, their discovery dictates that lymph nodes in the porta hepatis should be routinely excised because nearly 50% of patients will have lymph node metastases.