Zollinger-Ellison syndrome in the era of effective acid suppression: are we unknowingly growing tumors?

Effective medical therapy of gastric hypersecretion in Zollinger-Ellison syndrome may delay the diagnosis of gastrinoma. To examine the impact of effective medical therapy on the surgical treatment of gastrinoma we reviewed the records of 108 patients diagnosed between 1948 and 1998 at a single institution. Minimum follow-up was 5 years. The experience was divided into four periods: I, 1955-1965-initial recognition, n = 11; II, 1966-1975-increasing recognition, n = 27; III, 1976-1985-widespread application of gastrin radioimmunoassay, n = 21; and IV, 1986-1998-widespread use of effective medical therapy, n = 49. There was no significant difference in age or sex in the groups. Gastric surgery was less common in period IV (37% compared with 86% to 100% in previous periods) as was total gastrectomy (6% compared with 43% to 78%; P <0.0001). Tumor resection was attempted in a similar percentage of patients in each group (57% to 67%). The incidence of metastatic disease in period III was 19% (P = 0.034 versus period I, 45%, period II, 56%, and period IV, 55%). The 5-year disease-free survival increased in period III to 29% (P = 0.001 versus period I, 0%, period II, 4%, and period IV, 2%). The results support the effectiveness of acid suppressive therapy by H2 antagonists and proton pump inhibitors as evidenced by the decrease in gastric surgery. However, in the era of effective medical therapy, the surgeon sees the patient with more advanced disease and 5-year cure is less likely. Physicians must maintain a high index of suspicion for this disease and not mask a potential malignancy with prolonged control of acid-related symptoms without taking steps to diagnose gastrinoma.