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Treatment Option Overview

Localized Disease

If technically and medically feasible, primary management of endocrine tumors of the pancreas involves surgical resection with curative intent. Given the rare nature of these tumors, surgical approaches are based upon case series and expert opinion rather than randomized controlled trials.[1] The surgical options listed below are based on retrospective series from single reporting centers.[2,3,4][Level of evidence: 3iiD or 3iiiD]

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Adjuvant therapy has no proven benefit and is, therefore, investigational. There have been no well-controlled trials of adjuvant therapy after complete tumor resection.[5]

Surgical Cytoreduction for Metastases

Surgery plays a role even in the setting of metastatic disease. The symptoms of metastatic functional pancreatic neuroendocrine tumors (NETs) may be ameliorated by the reduction of overall tumor burden through surgical debulking.

The liver is a common site of metastasis from pancreatic NETs. Because of the slow growth rate of many NETs, liver metastases are often resected when technically feasible. Resection of all grossly visible liver metastases can be associated with long-term survival and, in the case of symptomatic hormonally functional tumors, symptom relief.[6] Most symptoms from functional tumors respond to this form of surgical debulking. How much of the favorable survival rates is attributable to patient selection factors is not known (e.g., underlying patient condition, extent of metastases, slow doubling time, and so forth).

A variety of alternative approaches to the management of liver metastases have been reported, including gel-foam embolization or transarterial chemoembolization,[7] radioembolization with radioactive microspheres,[8,9,10] radiofrequency ablation, cryoablation, and percutaneous alcohol ablation. These alternative approaches have been reviewed.[11]

Results from surgical resection series appear to be more favorable than with these techniques, and surgery is considered to be the standard approach to resectable liver metastases. However, there are no high-quality studies comparing the various approaches. A systematic review of evidence comparing liver resection versus other treatments for patients with resectable liver neuroendocrine metastases found no randomized trials, or even quasi-experimental, cohort, or case-control studies in which the patient population given the alternative therapies was similar enough to the surgery group to draw reliable conclusions.[12] The evidence for resection of all grossly visible liver metastases derives solely from case series.[Level of evidence: 3iiD or 3iiiD]

In most cases, liver metastases are not completely resectable. Cytoreductive surgery, with or without radiofrequency ablation or cryoablation, has been used to palliate symptoms. A systematic review found no randomized or quasi-randomized trials comparing cytoreductive surgery to other palliative approaches such as chemotherapy or tumor product inhibitors.[13] The evidence for surgical cytoreduction of unresectable liver metastases is restricted to case series [Level of evidence: 3iiD or 3iiiD], and interpretation of outcomes may be strongly affected by patient selection factors.

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