| ObjectiveTo study the mechanism and efficacy of treatment with microwave ablation(MWA) combination recombinant human interleukin-2 (rhIL-2) for mice transplanted hepatocarcinoma 22 (H22).Then, to explore its efficacy, feasibility and safety of cinical application, and provide a new therapy for primary hepatic carcinoma.MethodsA mouse model of liver cancer was established by subcutaneous injection of H22 cells.H22 bearing mice were randomly divided into four groups:control group, alone MWA group, alone rhIL-2 group and combination group,30 mice in every group. The tumors were subjected to microwave ablation (70 Watts,60 Secs) once on day 8 after injection of H22 cells in the MWA group. The rhIL-2(1000Units/day) was injected in abdomen of tumor-bearing mice by subcutaneous injection on days 8-14(7 times in all) in the rhIL-2 group. The mice in the combination group received all the processes of treatment in the MWA group and rhIL-2 group. The mice were not treated in the control group. 15 mice were selected by random sampling in every group. The mice were euthanized on day 21, and the weight of thymus gland and spleen, the growth rate, weight and size of tumor mass were measured, and the T lymphocyte subgroups were determined by flow cytometry. The tumor-inhibition rate, thymus index and spleen index in mice were reckoned. The changes of pathological characteristics and immunocytes on tumors were observed by Hematoxylin-Eosin and Immuno-histochemistry staining. The other 15 mice which were used to observe survival time were not euthanized in every group.67 cases of primary hepatic carcinoma were randomly divided into 2 groups by odd or even hospitalization number. A total of 32 patients were enrolled in the combining therapy group (underwent treatment by MWA in combination with rhIL-2) and 35 patients in the control group (MWA only group). The patients were treated by microwave ablation 1-2 times in the control group, and the patients (combining therapy group) were treated by the rhIL-2(0.2 million Units/day,14 times in all) after microwave ablation. In order to evaluate the safety and feasibility, the pain or not, shin burn, perforation of intestine and stomach were inspected. The changes of symptom, weight, grade of Karnofsky were monitored before and after treat, and liver function, alpha-fetoprotein, the appearance of liver CT, survival time so as to assess efficacy.ResultsThe growth rate, weight and size of tumor were significantly different in different treated group. The tumors weight in alone MWA group, alone rhIL-2 group and combination group were lighter than that in control group, P<0.01, the tumor-inhibition rates were 29.03%,39.39%, and 67.40% respectively. The thymus index and spleen index were higher in all the treated groups than that in control group, P<0.05. The T lymphocyte subgroups were significantly different in different treated group. The CD3+T cells were significantly increased in combination group and alone rhIL-2 group compared with the control mice by analysis of variance and Student-Newman-Keuls test, P<0.01. The CD4+T cells were significantly increased in the mice were treated vs the control group, P <0.01, there was significantly different between combination group, alone treated group and control group, P<0.01, but the CD8+T lymphocyte was decreased compared with the control mice, P<0.05. The ratio of CD4+/CD8+was significantly different in the four groups, P<0.01,the NK cells were significantly increased in treated groups compared with the control mice, there was significantly different between two groups in all the mice,P<0.01. The pathological characteristics and immunocytes on tumors were significantly different in different group. More of the rapid reproduction of tumor cells were found in the control group, and extensive coagulation necrosis cells were found in the MWA group, but the rapid reproduction of tumor cells in rhIL-2 group were smaller than that in the control group, both of the characteristics in the two alone treated group were found in the combination group. More CD4 positive cells were observed by Immuno-histochemistry staining in the treated group than that in the control group, but fewer CD8 positive cells were observed in the treated group. Survival time was significantly different in different treated group, and it was longer in the treated group than that in the control group. There were no serious complications microwave-induced such as skin burns, massive hemorrhage or damage to the stomach in 67 patients. The 0.5-year, 1-year, and 2-year survival rates were 84.38%,62.50%, and 28.13% in the combination group, and it was 74.29%,37.14%, and 14.29% in the control group, respectively. The 0.5-year,1-year, and 2-year cumulative recurrence rates were 15.63%,28.13%, and 59.38% in the combination group, and it was 22.86%, 54.29%, and 83.86% in the control group, respectively.ConclusionThe microwave ablation combined with rhIL-2 is safe, effective and feasible. It can improve the anti-tumor immunity in tumor-bearing mice. The microwave ablation combined with rhIL-2 is an effective and safe method to treat primary hepatic carcinoma. It can increase survival periods and reduce recurrence rate in patients with hepatocelluar carcinoma. |
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