| BackgroundThe development of primary hepatic carcinoma is a process with multiple factor, multiple stage, polygenic variation, close correlated with immune state, especially T lymphocyte cell. The process is regulated by multiple factor, accompanied with confused immune state to some extent. Majority scholar think that cell mediated immunity occupy the master position in immune. Some research showed the proportion and metergasis of T lymphocyte cells and NK cells are close related with the development and diffusion of tumor. And some research showed that of T lymphocyte subsets in peripheral blood in patients with HCC, CD3 and CD4 degraded, CD8 increased, immune function was weak, that was the major cause of weak immune of which tumor cells resulted in immune suppression.Tumor immunity is related with T lymphocyte cell mediated immunity in major, which reflect organism immune function. T lymphocyte subsets are consist of different subsets, especially CD4/CD8. It is the sensitive reflection against the balance of cell mediated immunity. CD4+T lymphocyte cells are the core of the cell mediated immunity, which regulate immunoreactive function by excreting cytokine, named helper T lymphocyte. Th is the restriction T lymphocyte of major histocompatibility antigen(MHC)classâ…¡molecule. Because most tumor cells do not present MHCâ…¡, this kind molecule do not direct identify tumor cells, but rely on antigen presenting cell, such as B lymphocyte, macrophagus to present related antigen and secret lymphokine, interleukin-2, r-interferon, and so on, so that activate B lymphocyte, macrophagus, NK cell to play its effective resisting tumor.Substantial evidence that has been expressed indicates that the cell apoptosis is related with the development of the tumor, the occurrence of the tumor closely, and hepatoma carcinoma cells cultured in vitro and esoteric all existed phenomenon of apoptosis. Spontaneous malignant cell apoptosis happened to hepatoma untreated, and malignancy to much more extent, higher index of apoptosis. It is positive correlation between proliferation index and apoptotic index in liver cancer. From normal liver to lesion precancerous and hepatoma, apoptosis percentage increased as proliferation increased. It is obviously higher of apoptosis in liver cancer tumor tissue than in the normal liver tissue. There are two sides of apoptois probably, one side restraining growth, another eliminating weak vitality tumor cells so that strong invasiveness tumor cells cloning and developing. So to study the mechanism and effectiveness of apoptosis could supply an important theory basis on new pathway of tumor treatment.Primary hepatic carcinoma is one of the most common malignant tumors in our country. Any single therapeutic tool is not satisfactory with liver cancer for the characteristic of easy metastasis and recurrence. Transcatheter arterial chemoembolizaton, TACE, is the first of chosen treatment methods, but there are still insufficenicy of embolization in many cases which lipiodol chemotherapeutics emulsion deposited in tumor focus is not enough so that rapid hyperplasy in tumor focus without lipiodol deposited. So it is the major cause of treatment failure and recurrence progression in local tumor region to the patients with liver cancer. There were any investigations implanting cytotoxic drug or biological agents directly into tumor tissue or peripheral interstitial substance recently, that is interstitial therapy, IT, forming the slow-release chemotherapy which killed tumor cells in local tumor region by slow released chemotherapy and sustained high concentrate agents.Transcatheter arterial chemoembolizaton, TACE, is the first selection to unable removal hepatoma. After TACE, a large amount of tumor cells were killed, coagulation necrosis in tumor appeared and tumor cell burden alleviate, so immune suppression factors, TNF, decreased and weakened its influence to immune function. But Transcatheter arterial chemoembolizaton include chemo and embolization which make influence to organism immune function complex.Lipiodol is a kind of fatty acid aethyl conjulin with iodine contents about 37%-39%. There is property of lipiodol not penetrated by X-ray, monitoring its diffusion scope at the proper moment through X-ray, being detained long term in tumor tissue, not easy to be missing activity and specificity for tumor cell mutation. So lipiodol is a better carrier adapted to injection into tumor, it can surround tumor cell to hinder material and oxygen exchange, then make cells hydropsia, fatty degeneration and death. But there were only few basic researches about percutaneous chemotherapic agents lipiodol emulsion injection.On another respect, common standpoint of the mechanism of TACE is that local chemoembolization bring up the tumor cells necrosis. But recently it was found that ischemic and oxygen deficiency were the reason of inducing tumor cells apoptosis, immediate early gene expression for several minutes after ischemic and oxygen deficiency. Ischemic and oxygen deficiency could induce more than 80 gene expression including that expression of gene promoting apoptosis increases and expression of gene restraining apoptosis descend. So apoptosis play an important role in tumor tissue necrosis due to TACE in patients with hepatoma. And it is an important mechanism to TACE probably of the apoptosis induced by TACE.We combined TACE with percutaneous chemotherapic agents lipiodol emulsion injection to make interstitial therapy in liver cancer, in order to approach the clinic curative effect of this sequential therapy and pathological change in one side, to explore the characteristics and significances in immunology changes of blood subgroups of lymphocyte T, to explore significances and effective of the tumor cell apoptosis induced by the treatment method in another side. We got the clinic research and basic research together, that is special feature, new ideals in our study, and not yet reported.ObjectiveTo study the clinic curative effect by transcatheter arterial chemoembolizaton combined with interstitial therapy for liver cancer and pathological change first, to explore the characteristics and significances in immunology changes of blood subgroups of lymphocyte T, to explore significances and effective of the tumor cell apoptosis induced by the this sequential therapy secondly.Methods60 patients with liver cancer were divided into two groups, A group received transcatheter arterial chemoembolizaton, and B group received transcatheter arterial chemoembolizaton combined with interstitial therapy of percutaneous lipiodol and anti-cancer agents injection intratumorly for liver cancer. Then to observe the percent of lipiodol deposited in the tumor, local control ratio of 6 months, survive rate in 2 years, the median survival time, adverse effect, and puncher biopsy one month postoperative. T lymphocyte cell subsets, CD3+, CD4+,CD8+, CD4+/CD8+ in the peripheral blood before and one week after operation were measured by flow cytometry; immune globulin determined by single radial immunodiffusion. The apoptosis percentage, death percentage of tumor cells was measured by flow cytometry with Annexin V/PI staining.ResultsThere was significant difference in the percent of fever between two groups, P< 0.01, normal temperature 7 instances in A group, low fever 3 instance, middle lever 7 instances, high lever 13 instances; normal temperature 16 instances in B group, low fever 8 instance, middle lever 4 instances, high lever 2 instances. There was no significant difference of WBC, HB, PLB preoperative in both A and B groups (P> 0.05).There was significant difference of WBC, HB between preoperative and postoperative in both A and B groups (P<0.05). And significant difference of WBC, HB between A and B group postoperative (P<0.05). It was higher of WBC in A group preoperative than postoperative, there was significant difference, P<0.05, but in B group there was no significant difference, P>0.05. And it was higher of HB in A group preoperative than postoperative, there was significant difference, P<0.05, but in B group there was no significant difference, P>0.05. There was significant difference in the percent of lipiodol deposited in the tumor, local control ratio of 6 months, survive rate in 2 years, the median survival time between A and B groups (P <0.05). There was significant difference in the rate of AFP degrade between A and B groups (P<0.05) postoperative. There is 13,17examples respectively in A group the rate of AFP degrade<50%,>50%, and B group 5,25 respectively. And there was a great quantity of coagulation necrosis of tumor focus in A group pathology postoperative, but a great quantity of lipoid degeneration necrosis in B group pathology postoperative. It was higher of CD3, CD4, CD4/8 in postoperative than in preoperative of both A and B groups. There was significant difference of CD3, CD4, CD4/CD8 between preoperative and postoperative in both A and B groups (P<0.05). And significant difference between A and B group postoperative exclude CD8 (P< 0.05). It was higher of immune globulin in postoperative than in preoperative of both A and B groups. But there was no significant difference between postoperative and preoperative of A group (P>0.05); immune globulin exclude C3significant difference between postoperative and preoperative of B group (P<0.05). It was no less in A group than in B group of the apoptosis percentage in normal tissue. There was no significant difference of the apoptosis percentage in normal tissue between A and B group (P>0.05). But it was higher in A group than in B group of the necrosis percentage in tumor edge. There was very significant difference of the necrosis percentage in tumor edge between A and B group (P<0.01). It was higher in B group than in A group of the apoptosis percentage in tumor edge. There was very significant difference of the apoptosis percentage in tumor edge between A and B group(P<0.05).ConclusionsThere was no less influence on humoral-mediated immunity in single TACE than associated with percutaneous chemotherapic agents lipiodol emulsion injection to make interstitial therapy in liver cancer. This sequence method of treatment could improve cell-mediated immunity and humoral immune function to much more extent. Transcatheter arterial chemoembolizaton combined with interstitial therapy of percutaneous lipiodol and anti-cancer agents injection intratumorly for liver cancer may improve the percent of lipiodol deposited in the tumor, local control ratio of 6 months, and to extend life span, to drop recurrence rate of remained focus tumor, to relieve adverse effect postoperative. So inducing the tumor cell apoptosis and improving immune function by TACE associated with interstitial therapy is the one of the major mechanisms treating liver cancer possibly. |
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