Regulative Effect Of Argon-helium Cryoablation On The Immune Responses Against Tumors

Argon-helium cryoablation is a freezing and thawing method utilizing the heat absorption which is induced by the rapid gas-liquid conversion of argon gas(the Joule-Thomson effect) with the help of imaging devices of direct visualization. Metabolic pathways are hampered by the damage of cytomembrance and cytoskeleton, and consequently lead to hyperosmosis-induced necrosis and organelles-damage-induced apoptosis. Closed intracellular antigen will be exposed after the cell death and captured by mature APC(Antigen presenting cells), and then the immune responses will be activated with the help of various inflammatory factors and immune cells. The physical effects of argon-helium cryoablation is proved by both imaging and pathology, however, the immune aspects still remained controversial. The purpose of this study is to investigate pathological changes of tumor cells as well as the immune response post-cryoablation, and to provide solid theoretical basis for the clinical application of argon-helium cryoablation.Part I Effect of argon-helium cryoablation on malignant glioma cells of mouseObjective: This study purpose was to investigate the difference effect in vivo apoptotic processes in glioma tissues following argon-helium cryoablation and chemotherapeutics.Methods:(1) Human malignant glioma U87 cell transplanted in right subcutaneous back of nude mice(n=24). When tumor diameter increased to 1.5 cm, tumor was tested by Radiology and Pathology in vivo.(2) The rats were randomly divided into two groups. One group received percutaneous cryoablation and another group received cisplatin injection.(3) Then after 3 days, sacrificed mice and TUNEL staining was performed to detect the apoptotic processes in the glioma tissues following different treatment.Results:(1) The apoptotic of two teams were different, the cryoablation team distributed mainly in R2 area but the distribution of the chemotherapeutics team distributed in R1 area was more obviously.(2) There was obviously different between two groups in the same area, p<0.05. But the apoptotic had no statistical difference, totally, between two groups, P=0.153.Conclusion:Cryoablation and chemotherapeutics had different influence in the same area of glioma tissues in touching off cell damage. The difference distribution of cell apoptotic in target area was the “trigger role” in leading to following immune of body.Part II Effect of advanced malignant tumor patient following percutaneous argon-helium cryoablationObjective:(1) To observe the response of tumor patient’s immune responses against tumors following percutaneous argon-helium cryoablation.(2) The effect of advanced malignant tumor patient following percutaneous argon-helium cryoablation.Methods:(1) Inclusion criteria: a definite diagnosis of tumor, without autoimmune diseases or serves angiocardiopathy; age from thirty-eight to sixty-nine year; KPS score ≥ fifty; expected survival time would be more than three months; blood count, the tests of blood coagulation, the tests of myocardial enzymes etc. were normal; without refractory ascites or and pleural effusion; without subcutaneous metastasis.(2) Number of cases for research: 122 patients, 159 lesions with advanced of hepatocarcinoma(n=45)or renal carcinoma(n=77)undergone CT guided percutaneous argon-helium cryoablation.(3) Indicators for Detection: Monitored the percentage changing of peripheral blood CD3+, CD4+, CD8+ T-lymphocyte subset and the proportional changing of CD4+/CD8+ T-lymphocyte by flowing cytometer respectively, 2 hours before and 20 hours after the argon-helium cryoablation.(4) Follow-up plan after operation: after operation, evaluated the short-term effects, made following up of progression free survival time and survival analysis.Results:(1) The percentage of peripheral blood CD3+、CD4+ and CD3+、CD8+ T-lymphocyte were significantly increasing after argon-helium cryoablation, measured by matched t-test, p<0.05.(2) The ratio of CD4+/CD8+ T-lymphocyte cells had an increase of 0.130, but p=0.069, had not statistical difference.(3) The total effective rate of advanced hepatocarcinoma team was 46.7%. The total effective rate of advanced renal carcinoma team was 44.2%. The KPS score of advanced hepatocarcinoma team had increased obviously, P=0.033. The KPS score of advanced renal carcinoma team had increased slightly, P=0.205, without statistical significance.(4) The result of following up: the following up time of advanced hepatocarcinoma team was 12 months and median survival time was 4.4 months. The following up time of advanced renal carcinoma team was 7 months and median survival time was 3.2 months.Conclusion:Percentage of blood T-lymphocyte subset of patients with advanced hepatocellular carcinoma or renal carcinoma had increasing significantly, when they was treated by using CT guided percutaneous cryoablation. The patient’s tumor specific immunity had enhanced by CT guided percutaneous cryoablation. The short-term effects, median survival times of patients had reached mean level.