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.