Cryosurgical palliation of metastatic neuroendocrine tumors resistant to conventional therapy

Background. Hepatic cryosurgery is a well-recognized modality for hepatic colon metastases. We examined its potential use for refractory neuroendocrine tumors causing progressive symptoms. Methods. Between July 1992 and February 1997, 19 patients (with islet cell, 7; carcinoid, 8; vasoactive intestinal peptide, 1; gastrinoma, 3) underwent cryosurgery with ultrasonography. The number of lesions frozen ranged from 1 to 16 (median, 8), and their diameters ranged from 2 to 15 cm with an average of 4 cm. Patients underwent resection of the primary tumor either before (37%) or concurrent with (32%) cryosurgery, and half underwent excision of metastases with cryosurery. Before cryosurgery, patients received chemotherapy (63%), somatostatin (47%), interferon (10%), hepatic artery ligation (5%), radiation (10%), and/or omeprazole (16%). Results. The reduction in tumor markers reached 90% (5-hydroxyindoleacetic acid), 80% (vasoactive intestinal peptide), 90% (gastrin), 90% (pancreatic polypeptide), and 80% (serotonin). At a median follow-up of 17 months, the metastases had progressed in 11 patients (two underwent a second cryosurgical procedure that eliminated symptoms) and five had died. Subsequently an additional five patients received chemotherapy and three somatostatin. Median symptom-free and overall survival were 10 months and more than 49 months, respectively. Conclusions. Cryosurgery dramatically relieved symptoms with significant reduction in tumor markers. The reduced tumor burden may explain the subsequent response to systemic therapy. Cryosurgery is a useful adjuvant in symptomatic patients with refractory hepatic neuroendocrine metastases.