Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors

Abstract

BACKGROUND: There is considerable controversy about the treatment of patients with malignant advanced neuroendocrine tumors of the pancreas and duodenum. Aggressive surgery remains a potentially efficacious antitumor therapy but is rarely performed because of its possible morbidity and mortality. HYPOTHESIS: Aggressive resection of advanced neuroendocrine tumors can be performed with acceptable morbidity and mortality rates and may lead to extended survival. DESIGN: The medical records of patients with advanced neuroendocrine tumors who underwent surgery between 1997 and 2002 by a single surgeon at the University of California, San Francisco, were reviewed in an institutional review board-approved protocol. MAIN OUTCOME MEASURES: Surgical procedure, pathologic characteristics, complications, mortality rates, and disease-free and overall survival rates were recorded. Disease-free survival was defined as no tumor identified on radiological imaging studies and no detectable abnormal hormone levels. Proportions were compared statistically using the Fisher exact test. Kaplan-Meier curves were used to estimate survival rates. RESULTS: Twenty patients were identified (11 men and 9 women). Of these, 10 (50%) had gastrinoma, 1 had insulinoma, and the remainder had nonfunctional tumors; 2 had multiple endocrine neoplasia type 1, and 1 had von Hippel-Lindau disease. The mean age was 55 years (range, 34-72 years). In 10 patients (50%), tumors were thought to be unresectable according to radiological imaging studies because of multiple bilobar liver metastases (n = 6), superior mesenteric vein invasion (n = 3), and extensive nodal metastases (n = 1). Tumors were completely removed in 15 patients (75%). Surgical procedures included 8 proximal pancreatectomies (pancreatoduodenectomy or whipple procedure), 3 total pancreatectomies, 9 distal pancreatectomies, and 3 tumor enucleations from the pancreatic head. Superior mesenteric vein reconstruction was done in 3 patients. Liver resections were done in 6 patients, and an extended periaortic node dissection was performed in 1. The spleen was removed in 11 patients, and the left kidney was removed as a result of tumor metastases in 2. Eighteen patients had primary pancreatic tumors, and 2 had duodenal tumors; 2 patients with multiple endocrine neoplasia type 1 had both pancreatic and duodenal tumors. The mean tumor size was 8 cm (range, 0.5-23 cm). Of the patients, 14 (70%) had lymph node metastases and 8 (40%) had liver metastases. The mean postoperative hospital stay was 11.5 days (range, 6-26 days). Six patients (30%) had postoperative complications. There was a significantly greater incidence of pancreatic fistulas with enucleations compared with resections (P =.04). There were no operative deaths. The mean follow-up period was 19 months (range, 1-96 months); 18 patients (90%) are alive, 2 died of progressive tumor, and 12 (60%) are disease-free. The actuarial overall survival rate is 80% at 5 years, and disease-free survival rates indicate that all tumors will recur by the 7-year follow-up visit. CONCLUSIONS: Aggressive surgery including pancreatectomy, splenectomy, superior mesenteric vein reconstruction, and liver resection can be done with acceptable morbidity and low mortality rates for patients with advanced neuroendocrine tumors. Although survival rates following surgery are excellent, most patients will develop a recurrent tumor. These findings suggest that conventional contraindications to surgical resection, such as superior mesenteric vein invasion and nodal or distant metastases, should be reconsidered in patients with advanced neuroendocrine tumors.