Expansion of an ablated site and induction of apoptosis after microwave coagulation therapy in rat liver

Background/Purpose: Microwave coagulation therapy (MCT), one of the ablation therapies, has been widely used to treat liver cancers, yielding excellent clinical results. Despite its efficacy, the precise events that take place in the ablated liver after MCT remain unknown. We investigated sequential histologic changes around MCT sites and the relationship between MCT and apoptosis in rat liver. Methods: One session of MCT at 30 W was applied to rat liver. The rats were killed at 0, 2, 6, 12, 24, 72, and 168 h after MCT. The liver surface area was measured for sequential evaluations of the size of the impaired field (i.e., the liver surface affected by MCT). The size of the impaired field was assessed by measuring the area that showed macroscopic changes in color with a relatively clear border. To assess apoptosis, we examined terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling stained sections, determined the positive cell count for DNA fragmentation, and observed DNA ladder formation by gel electrophoresis. Caspase-3 activity at the ablated margin was measured for the enzymatic evaluation of apoptosis. Results: The impaired field gradually expanded through 12 h after MCT. Caspase-3 activity increased four fold from the baseline, peaking at 2 h after MCT, and DNA fragmentation, confirmed by DNA ladder formation, was significantly increased at 6 h. Conclusions: Alterations in the ablated liver tissue indicated that the activation of caspase-3 around the MCT site was followed by apoptosis and expansion of the impaired field. The expansion continued until 12 h after MCT, and this may be beneficial for the local control of liver cancer. Received: March 22, 2001 / Accepted: June 6, 2001