BACKGROUND: The nonparenchymal cells (NPCs) of the liver have a strong cytotoxic activity. Our hypothesis is that their activity, which prevents metastases to the liver, may be impaired after operation. METHODS: First, Sprague-Dawley rats underwent either a sham operation consisting of only a laparotomy (group L, n = 10), a laparotomy and resection of a portion of the small intestine (group R, n = 10) or no operation (group C, n = 10). After 2 days liver NPCs were isolated and divided into two fractions, large and small NPCs. The cytotoxicity of the liver NPCs and of the circulating blood mononuclear cells (BMC) was assessed. Second, we measured the growth of tumor metastases 14 days after the inoculation of a cell line (MRMT-1) into the portal vein of rats undergoing similar surgical stress (group Rm, n = 10 and group Lm, n = 10). RESULTS: The natural killer cell activity (anti-YAC-1) of large NPCs was 38% in group R, which was significantly less (p < 0.002) than that in groups L (72%) and C (83%). Small NPCs showed reduced natural killer activity in groups R and L (26% and 35%, respectively) compared with that in group C (70%) (p < 0.02). The natural killer cell activity of BMCs was similar in each group, and the lymphokine-activated killer cell activity (by anti-EL4) did not change in either the NPCs or BMCs. In the second experiment the area of the tumors occupied in the liver in the group Rm rats was significantly greater compared with that in the group Lm rats (p < 0.01). CONCLUSIONS: Surgical stress depressed the cytotoxic activity of liver NPCs and enhanced the growth of metastatic liver tumors. This suggests the possibility that perioperative immunotherapy might be clinically useful in the future to prevent liver metastases after gastrointestinal surgery.
BACKGROUND: The nonparenchymal cells (NPCs) of the liver have a strong cytotoxic activity. Our hypothesis is that their activity, which prevents metastases to the liver, may be impaired after operation. METHODS: First, Sprague-Dawley rats underwent either a sham operation consisting of only a laparotomy (group L, n = 10), a laparotomy and resection of a portion of the small intestine (group R, n = 10) or no operation (group C, n = 10). After 2 days liver NPCs were isolated and divided into two fractions, large and small NPCs. The cytotoxicity of the liver NPCs and of the circulating blood mononuclear cells (BMC) was assessed. Second, we measured the growth of tumor metastases 14 days after the inoculation of a cell line (MRMT-1) into the portal vein of rats undergoing similar surgical stress (group Rm, n = 10 and group Lm, n = 10). RESULTS: The natural killer cell activity (anti-YAC-1) of large NPCs was 38% in group R, which was significantly less (p < 0.002) than that in groups L (72%) and C (83%). Small NPCs showed reduced natural killer activity in groups R and L (26% and 35%, respectively) compared with that in group C (70%) (p < 0.02). The natural killer cell activity of BMCs was similar in each group, and the lymphokine-activated killer cell activity (by anti-EL4) did not change in either the NPCs or BMCs. In the second experiment the area of the tumors occupied in the liver in the group Rm rats was significantly greater compared with that in the group Lm rats (p < 0.01). CONCLUSIONS: Surgical stress depressed the cytotoxic activity of liver NPCs and enhanced the growth of metastatic liver tumors. This suggests the possibility that perioperative immunotherapy might be clinically useful in the future to prevent liver metastases after gastrointestinal surgery.