Pancreatic Neuroendocrine Tumors : Surgical Treatment and Follow-up

Abstract: Pancreatic neuroendocrine tumors (Pan-NET), are rare, heterogenous and derive from the hormone producing cells in the pancreas. The functioning tumors that overproduce hormones cause clinical syndromes with specific symptoms due to the hormonal production. However, the majority of patients have non-functioning tumors, and in lack of symptoms, these more often present with, or develop, liver metastases. This thesis focuses on treatment of metastasized pan-NET, stage IV, from a surgical perspective. As some patients operated on for localized disease eventually experience recurrence, it would also be beneficial to be able to predict which patients that are at a higher risk for recurrence.         In paper I, outcome after primary tumor resection in pan-NET patients, stage IV, was evaluated. An association between primary tumor resection and prolonged survival was found in patients, both before and after propensity score match. In paper II, outcome after hepatic resection and thermal hepatic ablation of liver metastases, in patients previously subjected to primary tumor resection, was scrutinized. Survival rates were significantly higher in the hepatic resection/thermal hepatic ablation group, and in a multivariable analysis, hepatic resection/thermal hepatic ablation remained a significant positive prognostic factor for prolonged survival. In paper III, patients with unresectable liver metastases, eligible for liver transplantation were investigated. A very small group of all pan-NET stage IV patients was eligible for liver transplantation and even fewer patients met any of the current selection criteria for liver transplantation. The survival rates for these patients, only subjected to multimodal treatment, were comparable to the survival rates after liver transplantation, presented in previously published studies. In paper IV, an external validation of a prediction model for recurrence after resection of non-metastatic, non-functioning, grade 1-2 tumors, was performed. The model performed well in the validation and is available online.To conclude, both primary tumor resection and surgical and ablative treatment of liver metastases in stage IV pan-NET, were associated with prolonged survival in analyses controlling for bias and possible confounders. However, the evidence base to perform liver transplantation in patients with pan-NET is weak. A prediction model for recurrence after radical surgery of non-metastatic pan-NET was externally validated with success. Our findings provide additional knowledge regarding treatment of stage IV pan-NET and could also help us predict which patients that will recur after surgery.