Cryoablation of malignant liver tumors: results of a single center study.

BACKGROUND: Local ablative procedures such as cryosurgery and thermo-ablation are increasingly employed as a supplement to liver resection for the therapy of primary and secondary liver tumors. It is still unclear if the survival time can be extended through local ablative procedures. This prospective study shows operative actions, complications and long-term follow-up of 19 patients undergoing cryotherapy. METHODS: Between 1997 and 1998, 19 patients underwent cryotherapy due to a non-resectable malignant liver tumor (17 patients with metastases of a colon carcinoma, 2 patients with a hepatocellular carcinoma). Twelve patients (63.2%) received cryotherapy only and seven patients (36.8%) received a combination of resection and cryotherapy. The median follow-up period was 23 months. RESULTS: In a total of 59 liver tumors (18 were resected and 41 received cryotherapy), 12 had cryotherapy only, and 7 had a combination of cryotherapy and resection. The 30-day lethality was 0%, and the rate of major complications was 21%. After one year, 27.3% of the patients were still recurrence-free. The recurrence rate for all tumors treated was 58.8%. The median survival time for all patients was 21 months. The one- and three-year survival rates were 62.5% and 15.8%, respectively. CONCLUSIONS: The mortality for cryotherapy is low, but there is a high rate of complications and long-term tumor control is not sufficient. If local ablative procedures of hepatic lesions are to be performed, not laparotomy but percutaneous, percutaneous thermoablation should be discussed as an alternative therapeutic measure.

Inhibition of tumor growth and angiogenesis by soluble EphB4.

EphB receptors and their ephrinB ligands play a key role in the formation of a regular vascular system. Recent studies have also shown the involvement of Eph/ephrin interactions in malignant tumor progression and angiogenesis. We have generated soluble monomeric EphB4 (sEphB4)-expressing A375 melanoma cells to study the effect of dominant negatively acting sEphB4 on tumor growth and angiogenesis. Soluble EphB4-expressing A375 tumors grown subcutaneously in nude mice show dramatically reduced tumor growth compared to control tumors. The proliferative capacity of sEphB4-expressing cells in monolayer culture is not altered. Yet, sEphB4-expressing A375 cells cannot establish proper cell-cell contacts in three-dimensional spheroids. However, sEphB4 transfectants have reduced proliferation and apoptosis rates when grown in three-dimensional culture in vitro or in subcutaneous tumors in vivo. Analysis of the vascular phenotype of the tumors revealed a reduction of intratumoral microvessel density in sEphB4-expressing tumors. Corresponding to these mouse experiments, a matched pair analysis of EphB4 and ephrinB2 expression in human colon carcinomas revealed significantly upregulated levels of EphB4 expression compared to adjacent normal tissue. Taken together, the data identify dual effects of sEphB4 on the tumor and the vascular compartment that collectively inhibit tumor growth.