| ObjectiveTo study the mechanism and efficacy of treatment with microwave ablation(MWA) combination 5-fluorouracil(5-FU) sustained-release implants 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 5-FU sustained-release implants group and combination group, 20 mice in every group. The tumors were subjected to microwave ablation (70 Watts, 60 Secs) once on day 10 after injection of H22 cells in the MWA group. Three 5-FU chemotherapy seeds about 6mg were planted with a special needle directly into the tumor on day 10 after injection of H22 cells in the 5-FU sustained-release implants group. The mice in the combination group received all the processes of treatment in the MWA group and 5-FU sustained-release implants group. The mice were not treated in the control group. 10 mice were selected by random sampling in every group. The tumor volume of every mice were measured after the treatment of the next day, and detected the tumor growth rate. Collected peripheral blood and killed the mice on day 23. The weight and size of tumor mass were measured, to calculate the inhibition rate of each treatment group.The weight of thymus gland and spleen were measured, to calculate the thymus and spleen index. The T lymphocyte subgroups of mice peripheral blood were measured by flow cytometry. The changes of pathological characteristics on tumors were observed by Hematoxylin-Eosin staining. The tumor cell apoptosis of each group were measured by apoptosis detection kit. The other 10 mice which were used to observe survival time were not euthanized in every group. 63 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 5-FU sustained-release implants) and 31 patients in the control group (MWA only group). The patients were treated by microwave ablation in the control group, and the patients (combining therapy group) were treated by the 5-FU sustained-release implants after microwave ablation. In order to evaluate the safety and feasibility, the pain or not, skin 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 combination group, MWA group and 5-FU sustained-release implants group were lighter than that in control group, P<0.05, the tumor-inhibition rates were 78.79%, 42.90%, 26.75%. The thymus index in all the treated groups were higher than that in control group, P<0.05. The spleen index in combination group, MWA group were higher than that in 5-FU sustained-release implants group and control group, P<0.05. After treatment, the T lymphocyte subgroups were changed different in different treated group. Analysis of variance, among groups using SNK (Student-Newman-Keuls) test,The CD4+T lymphocyte in combination group, MWA group were significantly increased than in 5-FU sustained-release implants group and control group, P <0.05. But the CD8+T lymphocyte were decreased, the combination group, MWA group compared with 5-FU sustained-release implants group, control group were statistically significant, P<0.05. The ratio of CD4+/CD8+ in all the treated groups were higher than that in control group, the difference was significant between groups, P <0.05.The NK cells were significantly increased in treated groups compared with the control mice, there was significant difference, P<0.05, but comparisons between treatment groups showed no significant difference.The pathological characteristics and cell apoptosis 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, the 5-FU sustained-release implants group showed small pieces of tumor cell necrosis and a large number of apoptosis, both of the characteristics in the two alone treated group were found in the combination 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 63 patients. Effective response rate of the combination group and the control group were 84.3%, 61.3%. The 0.5-year, 1-year, and 2-year survival rates were 81.3 %, 59.4%, 28.1% in the combination group, and it was 80.6%, 32.3%, 12.9% in the control group. The 0.5-year, 1-year, and 2-year cumulative recurrence rates were12.5 %, 25.0%, 56.3% in the combination group, and it was 22.6%, 58.1%, 83.9% in the control group.ConclusionThe microwave ablation combined with 5-FU sustained-release implants is safe, effective and feasible. It can improve the systemic anti-tumor immunity in mice. The microwave ablation combined with 5-FU sustained-release implants agent for the treatment of primary hepatic carcinoma, effect is obvious.It can increase survival periods and reduce recurrence rate in patients. |
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