Management of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

Introduction: Pancreatic endocrine tumors (PETs) occur in at least 50% of patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of disease-specific mortality. However, the timing and extent of surgery for MEN1-related PETs is controversial owing to the indolent tumor growth seen in most patients and the desire to avoid complications associated with insulin dependence. To help resolve this controversy, we retrospectively analyzed the clinical characteristics, surgical treatment, and clinical outcome of patients with MEN1-related PETs. Methods: All patients had histologic or radiographic confirmation of a PET in the setting of MEN1. Disease progression was defined radiographically as the development of new pancreatic tumors or distant metastases. Progression-free survival (PFS) and overall survival (OS) were used as the endpoints of this analysis. Results: We identified 98 patients with MEN1, 55 (56%) of whom had PETs, including 27 women and 28 men with a median age of 37 years (range 8-69 years) at the time of diagnosis. Functioning PETs were present in 35 (64%) of 55 patients, and nonfunctioning tumors were present in 20 (36%). Pancreatic surgery was performed in 38 (69%) of the 55 patients; and the first operation included enucleation (n = 4), total pancreatectomy (n = 3), Whipple procedure (n = 4), and distal pancreatectomy (n = 27). The median size of the resected tumors was 2.8 cm (range 0.6-11.0 cm). Recurrent disease developed in the residual pancreas in 7 (20%) of 35 at-risk patients a median of 7.8 years after the first operation, and distant metastases occurred in 5 (14 %) of 36 surgically treated patients without distant metastasis (2 patients had distant metastases when surgery on the primary tumor was performed) at a median of 2.7 years following surgery. At last follow-up, 16 (29%) of 55 patients with PETs had died, 12 (22%) were alive with disease, 26 (47%) were alive without evidence of disease, and 1 (2%) was lost to follow-up. The median OS was 19.5 years (range 13-26 years) and was significantly longer for patients who had functioning PETs versus those with nonfunctioning tumors (P = 0.0007), for patients who underwent surgical resection of their PETs versus those who did not (P = 0.0043), and for patients with localized versus metastatic PETs at the time of diagnosis (P < 0.0001). Multivariate analysis revealed that younger age, hormonal function, and PET resection were independently associated with longer OS. Conclusion: Our data suggest that early diagnosis and surgical excision of MEN1-related PETs improves survival. However, translating these data into a surveillance strategy for the early detection of PETs is complex owing to the potential morbidity of pancreatic resection and the risk of long-term insulin dependence.