Mechanism of metastatic spread by 42 degrees C total-body hyperthermia in Lewis lung carcinoma.

We investigated the mechanism of metastatic spread in Lewis lung carcinoma-bearing C57BL/6 mice exposed to 42 degrees C total-body hyperthermia (TBH) by water immersion. When the mice were treated with 42 degrees C TBH 24 h after resection of the primary tumor, the spread of lung metastasis was inhibited (P less than 0.01). When tumor-bearing mice were exposed to 42 degrees C TBH followed by resection of the primary tumors 24 h later, the spread of lung metastasis was greater than in the control group from which tumors were removed 6 days after inoculation (P less than 0.05). When normal mice were subjected to 42 degrees C TBH and Lewis lung carcinoma cells were subsequently injected i.v., lung metastasis increased significantly in those mice that had received tumor cell injection between immediately after and 48 h after TBH treatment (P less than 0.02-0.001). Tumor-bearing mice were subjected to 42 degrees C TBH, and changes in the lung tissues were examined. Between 12 and 48 h after TBH, alveolar collapse, edema, and cellular infiltration into the alveolar walls were seen. Tumor-bearing mice were exposed to 42 degrees C TBH and blood was taken from the inferior vena cava. The number of tumor cells in the blood increased significantly 12 h after TBH exposure (P less than 0.05). We suggest that TBH promotes the intravascular invasion of tumor cells and that histological changes in the host lung facilitate the implantation of tumor cells.