Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing Zollinger-Ellison syndrome

Purpose: The long-term clinical course of unselected patients with gastrino mas as well as other functional pancreatic endocrine tumors (PETs) in whom the excess-hormone stare is controlled is largely unknown, To address this issue, patients with gastrinomas were assessed, Patients and Methods: Two hundred twelve patients with Zollinger-Ellison sy ndrome (ZES) were prospectively studied, All had controlled acid hypersecre tion and were assessed yearly, with a mean follow-up period of 13.8 +/- 0.6 years (range, 0.1 to 31 years). Annual assessments of possible factors tha t might affect prognosis or treatment approaches were performed, such as th ose for tumor size and location; the presence, location, and extent of meta stases; and the occurrence of ectopic Gushing's syndrome or another PET syn drome. Deaths were categorized as ZES-related or non-ZES-related and classi fied into different causes. Results: Thirty-one percent of patients died, all of non-acid-related cause s. One half died of a ZES-related cause; they differed from those who died of non-ZES deaths by having a large primary tumor, more frequently a pancre atic tumor; lymph node, liver, or bone metastases; ectopic Gushing's syndro me; or higher gastrin levels, The extent of liver metastases correlated wit h survival rate, The presence of liver metastases alone only moderately dec reased survival time; however, the additional development of bone metastase s or ectopic Gushing's syndrome markedly decreased survival rate. Conclusions: In ZES, gastrinoma growth is now the main single determinant o f long-term survival, with one half of patients dying a gastrinoma-related death and none an acid-related death, Large primary tumors that are pancrea tic in location, the development of liver metastases, (especially if associ ated with bone metastases or Gushing's syndrome), and the extent of liver m etastases are all important prognostic factors, The identification of these factors allows the recognition of subgroups that can be used to tailor ant itumor treatment approaches. (C) 1999 by American Society of Clinical Oncol ogy.