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Management of metastatic disease from neuroendocrine cancers

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How is metastatic neuroendocrine tumors localized to the liver treated?

Liver metastases can be managed with "debulking" (removing as much tumor bulk as safely possible), either during the initial operation or a later date, and this is intended to relieve symptoms. (This contrasts with "ordinary" exocrine pancreas cancer, in which patients with metastases are not candidates for an operation to remove the tumor.) Alternative techniques for managing liver metastases include "radiofrequency ablation" (i.e., using special energy to super-heat tumors), "cryoablation" (freezing the tumor masses), and "chemoembolization" (injecting chemotherapy deposits directly into the blood vessels of the tumor), all of which have been successfully applied.

Surgical resection. Neuroendocrine cancers are one of a small number of tumors for which surgical debulking confers some survival advantage. Cytoreductive surgery, a mainstay in the management of widely metastatic disease, aims to control symptoms and improve survival by removing or destroying disseminated tumor metastases. In addition, the often-crippling symptoms associated with many of these tumors may be eased by decreasing tumor load. In a series of patients with unresectable disease who underwent surgical debulking, 50% of patients reported an improvement in symptoms for a mean duration of 39 months. Several reports have demonstrated for both pancreatic neuroendocrine and carcinoid tumors that palliative surgery elicited a hormonal response in virtually all patients with decreased pain in 90% of patients. This symptomatic improvement is especially important for patients with no medical options for managing their disease, such as the necrolytic migratory erythema of glucagonoma. Aggressive resection of hepatic metastatic disease seems to be associated with improved overall survival although this conclusion is not based on any randomized trials. Several centers report that the 5-year survival for patients treated with hepatic resection is around 70-80%. Most recommend to consider hepatic resection if more than 90% of the tumor can be excised and less than 75% of the liver is involved.

Hepatic artery embolization. The therapy of hepatic artery embolization (HAE) is predicated on the anatomical observation that most tumors within the hepatic parenchyma receive the bulk of their blood supply from the hepatic artery, whereas the portal vein supplies most of the normal hepatic parenchyma. Chemoembolization involves infusion of vaso-occlusive material into the hepatic artery to reduce blood supply to the tumor along with an infusion of high dose chemotherapy. Coils, gelfoam, polyvinyl alcohol, and iodinated oil have been used to embolize arteries with the addition of doxorubicin, cisplatin mitomycin C, streptozocin, and 5-fluorouracil. None of these combinations has produced significantly superior results. Contraindications to this procedure include tumor composing more than 50% of the hepatic volume, bilirubin greater than 2.0, AST greater than 100, or portal vein thrombosis. Multiple studies have shown reductions in hormonal levels in greater than 90% of patients. Unfortunately, these responses have lasted for little more than a year. Complication rates can approach 20%.

Liver transplantation. Hepatic metastases from malignant neuroendocrine tumors have been evaluated as an indication for liver transplantation. In one of the largest series of neuroendocrine tumors, 103 patients received liver transplants. Two and five-year survival was 60% and 47% respectively. Disease-free survival was 60% and one year and 23% at three years. Favorable prognostic factors included age less than 50 years old, primary tumor in the lung or bowel, and pretransplant treatment with somatostatin analogues.

Radiofrequency ablation (RFA). RFA provides a novel approach for those with limited hepatic involvement by utilizing selective thermal coagulation of tumor to destroy isolated metastases. In a retrospective study of patients with metastatic carcinoid and neuroendocrine pancreatic tumors, the investigators reports clearance of tumor in 17%-46% of patients. Likewise, symptom improvement was noted in 71% patients with carcinoid syndrome, and 75% also reduced their 5-HIAA and CgA by at least 50%. Similarly, though data in hepatic neuroendocrine metastases are limited to small series, several studies have demonstrated the effectiveness of RFA in the treatment of unresectable hepatocellular carcinomas and hepatic metastases of colon carcinoma.

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