| Chapter 1Objective:To investigate the efficacy of IRE and RFA ablation methods for pancreatic cancer.Methods:Mouse pancreatic cancer in situ model was established.The mice were divided into control group(n=5),IRE group(n=15)and RFA group(n=15).Nano-knife and radiofrequeney ablation were performed respectively to observe the pathological changes of pancreatic tumor tissue at l week after operation.Immunohistochemistry was used to detect the expression of Bcl-2,VEGF and HSP-70 in pancreatic tumor tissues.The expression levels of plasma Caspase-3,TNF-a and VEGF were detected by ELISA.Results:HE staining showed that the central area of RFA ablation was completely necrotic,and the nucleus was pyknosis,fragmented.IRE ablation lesions have clear boundary,and nuclear pyknosis,fragmentation.Plasma Caspase-3,TNF-a,and VEGF levels were significantly higher in the IRE and RFA groups than in the control group,especially in the IRE group(P<0.05 or 0.01).The positive expression rates of Bcl-2 and VEGF were significantly lower in the IRE group and the RFA group than in the control group.The positive expression rate of HSP-70 was significantly higher than that of the control group,and the IRE group was the most significant(P<0.05 or 0.01).Conclusion:In the mouse model of pancreatic cancer,IRE and RFA treatment can effectively reduce the tumor area.IRE treatment effect is better.Chapter 2Objective:To investigate the synergistic anti-tumor effect of IRE combined with albumin paclitaxel chemotherapy in mouse model of pancreatic cancer.Methods:Twenty-five mice were randomly divided into chemotherapy group,IRE+chemotherapy group,chemotherapy + IRE group,simple IRE group and blank control group.The pathological changes of the pancreatic tumor tissue were observed by HE staining.The expression of Caspase-3 and HSP-70 was detected by immunohistochemistry.The distribution of paclitaxel in each tissue was determined by high performance liquid chromatography(HPLC)analysis.Results:Compared with the chemotherapy alone group,Caspase-3 expression was significantly increased in the other three treatment groups(all P<0.01),while the HSP-70 expression levels in the two combined treatment groups were significantly decreased(all P<0.01).The results of HPLC showed that the expression of Caspase-3 in two combined treatment group was significantly higher than chemotherapy alone group(P<0.05 or 0.01).Conclusion:IRE combined with chemotherapy can effectively increase the expression of Caspase-3,down-regulate the expression of HSP-70 and increase the paclitaxel content in tumor tissue and blood,so as to enhance the anti-tumor effect and achieve the goal of targeted therapy.Therefore,Combined treatment has great potential clinical application value.Chapter 3Objective:To investigate the clinical efficacy of nano-knife ablation combined with chemotherapy in patients with locally advanced pancreatic cancer(LAPC).Methods:Forty-two patients with LAPC were enrolled.Twenty-two patients were treated with IRE alone and 20 patients were treated with IRE combined with chemotherapy.The objective efficacy and survival of the two groups were compared.Results:There was no significant difference in the total effective rate between the two groups(P>0.05),but there was a significant difference in the clinical benefit rate between the two groups(P<0.05).The median survival of IRE and IRE+chemotherapy groups was 6.3 months and 9.2 months,respectively(P<0.05).The difference in survival time between the two groups was statistically significant(x2=3.877,P<0.05).Conclusion:IRE combined with chemotherapy for LAPC prolongs the survival of patients. |