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The Mechanism And Clinical Application Of Irreversible Electroporation In The Treatment Of Locally Advanced Pancreatic Cancer

Posted on:2020-02-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:J J SuFull Text:PDF
GTID:1364330578971576Subject:Surgery
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Chapter 1Objective:To investigate the histopathological changes and ultrasonographic comparison of IRE ablation in orthotopic model of pancreatic cancer in nude mouse.Methods:Orthotopic model of pancreatic cancer was established.The nude mice were divided into control group(n=5),sham group(n=22)and IRE group(n=22).The pathological changes of pancreatic tumor tissues in each group at 1d,3d and 7d after surgery were observed.HE staining and immunohistochemical examination were performed.Imaging of each nude mouse before and after treatment with IRE was performed by ultrasound,and the changes of normal pancreatic tissue and tumor tissue before and after ablation were observed.Results:The results of HE staining showed that the IRE ablation area showed acute,extensive and severe pancreatic cell death,inflammatory cell infiltration,uniform tissue structure of the ablation area,providing a good scaffold for the formation of new tissue,and the surrounding tissue of the IRE ablation area had a good integrity.The positive expression rates of Ki67 and cleaved caspase-3 in pancreatic tumor tissues in the ablation area were significantly higher than those in the control group(P<0.05),indicating that IRE treatment could promote apoptosis of tumor cells and promote normal tissue regeneration.After IRE treatment of tumor tissue,ultrasound images showed that with the increase in the content of inflammatory cells and immune cells in the ablation area,the hyperechoic area became significantly higher than the preechogenic area.Conclusion:After IRE treatment in the Orthotopic model of pancreatic cancer,extensive necrosis of tumor cells in the ablation area can be achieved and normal tissue regeneration can be promoted,while the tissue framework structure in the ablation area is complete.Ultrasound images show tumor changes,and ultrasound can be used to assess the efficacy of ablation.Chapter 2Objective:To investigate the biological effects and immunological changes of pancreatic orthotopic tumor cells after irreversible electroporation.Methods:Thirty nude mice were randomly divided into two groups:control group(n=15)and IRE group(n=15):control group was treated with switch abdominal surgery,while nude mice in IRE group were treated with IRE.Nude mice in each group were then killed at different time points(1,3 or 7 days).Annexin V-FITC apoptosis assay kit was used for apoptosis analysis,and cck-8 assay was used to detect the proliferation capacity of splenic lymphocytes.Results:After IRE treatment,the apoptosis rate was 93.71%,which was significantly higher than that of the control group(3.37%,p<0.05).The transformation rate of splenic lymphocytes in the control group was lower than that of the IRE group(p<0.01).The transformation rate of splenic lymphocytes in the IRE group was higher than that of the control group(p<0.01).IRE may enhance the activity of B lymphocytes.Conclusion:IRE's anti-tumor effect in the Orthotopic model of pancreatic cancer can not only directly destroy tumor cells,but also inhibit tumor cells by increasing the conversion rate of spleen lymphocytes and stimulating the cellular immune function of the body.In the Orthotopic model of pancreatic cancer,IRE was effective in the treatment of targeted ablation of pancreatic tumor.Chapter 3Objective:To investigate the clinical effect of irreversible electroporation in the treatment of locally advanced pancreatic cancer.Methods:Thirty patients with locally advanced pancreatic cancer treated with IRE from July 2015 to December 2016 were selected as the study subjects,and 30 patients with locally advanced pancreatic cancer treated with chemotherapy alone during the same period were selected as the control group(matched pairs in 1:1).The objective efficacy,quality of life and survival were compared between the two groups.Results:The effective rate of pain relief in the IRE group(70%)was significantly higher than that in the chemotherapy group(46.6%).Compared with the chemotherapy group,the disease-free survival period of patients in the IRE ablation group was improved(6 months:4 months,P<0.05),and the overall survival period was significantly improved(11 months:5.6 months,P<0.05),the difference was statistically significant.Conclusion:IRE can alleviate pain in patients with locally advanced pancreatic cancer and improve disease-free survival of patients with locally advanced pancreatic cancer.IRE ablation for locally advanced pancreatic cancer is safe and can improve overall survival of patients compared with standard chemotherapy.
Keywords/Search Tags:Irreversible electroporation, Locally advanced pancreatic cancer, Diagnosis, Quality of life, Immune function, Apoptosis
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