New immunotherapy for prevention of liver metastasis from colorectal cancer after surgery.

（实验研究）东柳大鼠于第0天经门静脉接种AH-130肿瘤细胞，2 d后经门静脉（P组）或皮下间隙（S组）连续给予IL-2。对照组大鼠单独给予生理盐水（C组）。第8天，肝非实质细胞（NPC）的肝转移发生率和细胞毒性（NK、LAK和抗ah -130活性）均显著降低，P组与C组相比，NPC的肝转移发生率显著降低，NK、LAK和抗ah -130活性显著增强。而S组未见上述影响。用IL-2培养的ICR小鼠脾细胞和淋巴结淋巴细胞诱导LAK细胞。培养7 d的LAK细胞LAK活性约为70%。（临床研究）我们测定了结直肠癌门静脉引流中前列腺素E2 (PGE2) （n=23）水平和淋巴细胞亚群（n=10）。门静脉PGE2水平明显高于动脉。9例门静脉PGE2含量超过100pg/ml的患者中有4例在术后两年内发生肝转移。为了预防肝脏复发，4例结直肠癌肝转移患者在肝切除术后接受了IL-2、OK-432、阿霉素、环磷酰胺和法莫替丁的肝内联合免疫治疗。所有患者仍存活2年以上。综上所述，肝内联合免疫治疗可能有助于预防结直肠癌肝转移。门静脉PGE2水平可能是预测结直肠癌肝脏复发的新指标。

(Experimental study) Donryu rats were inoculated with AH-130 tumor cells on day 0 via the portal vein, and 2 days later, IL-2 was administered continuously via the portal vein (P group), or into the subcutaneous space (S group). Control rats were received saline alone (C group). On day 8, the incidence of liver metastasis and cytotoxicities (NK, LAK and anti-AH-130 activity) of liver non-parenchymal cells (NPC), In P groups, hepatic metastasis were significantly reduced, and NK, LAK and anti-AH-130 activities of NPC were significantly augmented compared with C group. However, these effects were not observed in S group. LAK cells were induced from splenocytes and lymphocytes of the lymph nodes using ICR mice, cultured with IL-2. LAK cells cultured for 7 days showed about 70% of LAK activity.(Clinical study) We determined prostaglandin E2 (PGE2) (n=23) levels and lymphocyte subsets (n=10) in portal venous drainage of colorectal cancer. The PGE2 levels in the portal vein were significantly higher than those in the artery. Four of nine patients with more than 100pg/ml of portal PGE2 developed liver metastasis within two years following surgery. For prevention of recurrence in the liver, four patients with liver metastasis from colorectal cancer received intrahepatic combined immunotherapy using IL-2, OK-432, adriamycin, cyclophosphamide, and famotidine after hepatectomy. All patients are still alive more than 2 years. In conclusion, intrahepatic combined immunotherapy may be useful for prevention of liver metastasis from colorectal cancer. PGE2 levels in the portal vein may be anew predictor for liver recurrence from colorectal cancer.