Prospective study of the natural history of gastrinoma in patients with MEN1: Definition of an aggressive and a nonaggressive form

The natural history of pancreatic endocrine tumors (PETS) in patients with MEN1 is largely unknown. Recent studies in patients with sporadic PETS show that in a subset, tumor growth is aggressive. To determine whether PETS in patients with MEN1 show similar growth behavior, we report results from a long-term prospective study of 57 patients with MEN1 and Zollinger-Ellison syndrome. All patients had tumor imaging studies yearly, and the mean follo w-up was 8 yr. Only patients with PETS 2.5 em or larger underwent abdominal surgical exploration. Hepatic metastases occurred in 23%, and in 14% tumor s demonstrated aggressive growth. Three tumor-related deaths occurred, each due to liver metastases, and in each, aggressive tumor growth was present. Overall, 4% of the study group, 23% with liver metastases and 38% with agg ressive disease, died. Aggressive growth was associated with higher gastrin s and larger tumors. Patients with liver metastases with aggressive growth differed from those with liver metastases without aggressive growth in age at MEN1 onset or diagnosis and primary tumor size. Survival was decreased ( P = 0.0012) in patients with aggressive tumor growth compared with those wi th liver metastases without aggressive growth or with no liver metastases w ithout aggressive growth. Based on these results a number of factors were i dentified that may be clinically useful in determining in which patients ag gressive tumor growth may occur. These results demonstrate in a significant subset of patients with MEN1 and Zollinger-Ellison syndrome, aggressive tu mor growth occurs and can lead to decreased survival. The identification of prognostic factors that identify this group will be important clinically i n allowing more aggressive treatment options to be instituted earlier.