| Background:Pancreatic cancer is a kind of digestive tract solid tumor with high malignant degree.Its onset is occult,early diagnosis is difficult,and the tumor is aggressive.Clinically,most of the patients were in the local advanced stage of pancreatic cancer or had distant metastasis,and lacked the opportunity for radical surgical resection.In recent years,the application of microwave ablation and other techniques in the treatment of locally advanced pancreatic cancer is limited due to the difficulty of ablation and the high incidence of postoperative complications.Therefore,it is necessary to find new therapeutic methods for locally advanced pancreatic cancer.Irreversible electroporation(IRE)is a new tumor ablation technology.Different from traditional ablation therapy,IRE has the advantages of no thermal side damage,no ionizing radiation,no pipeline damage,etc.Therefore,it is especially suitable for pancreatic cancer patients who cannot be radically resected.Objective:The purpose of this study was to explore the safety and effectiveness of Irreversible electroporation(IRE)in the treatment of pancreatic cancer,and to explore the effect of irreversible electroporation combined with adjuvant therapy on pancreatic cancer.Methods:The clinical data of 33 patients who underwent IRE treatment for unresectable pancreatic cancer admitted to the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Air Force Medical University from 2015 to 2022were collected.Blood biochemical indexes and postoperative complications of patients with IRE before and after surgery were analyzed.Blood biochemical indexes were analyzed in each group with different surgical methods.Meanwhile,relevant data of IRE surgery and postoperative complications in each group were analyzed to explore the safety of IRE in treating pancreatic cancer.The effectiveness of IRE in treating pancreatic cancer was explored by comparing the changes of tumor marker CA19-9 before and after surgery and in each group,as well as comparing the difference of IRE with radiotherapy and radiotherapy plus chemotherapy in the survival of pancreatic cancer patients.The survival time of patients treated with IRE combined with radiotherapy and chemotherapy,targeted therapy and immunotherapy(hereinafter referred to as adjuvant therapy)was further compared with those treated with IRE alone and those treated with radiotherapy and chemotherapy,so as to explore the effectiveness of IRE combined with adjuvant therapy for pancreatic cancer patients.Results:1.Among the 33 patients with pancreatic cancer treated with IRE,there were 17 males and 16 females,with a median age of 60(43-80)years.There were 27 cases of pancreatic head and neck tumor and 6 cases of pancreatic body and tail tumor,the tumor volume was 36.49±32.86cm~3.There were 20 patients(60.6%)with stageⅢpancreatic cancer and 13 patients(39.4%)with stageⅣpancreatic cancer.Ten patients received pure IRE,8 patients received IRE+fluorouracil,9patients received IRE+short-circuit surgery,and 6 patients received IRE+fluorouracil+short-circuit surgery.Of the 33 patients with pancreatic cancer,10(30.3%)received adjuvant therapy in addition to IRE,and 23(69.7%)only received IRE.2.The bilirubin level of 33 pancreatic cancer patients treated with IRE had no significant difference before and after surgery(P>0.05),while the level of transaminase,blood glucose and D-dimer were significantly increased after surgery(P<0.05),while the contents of hemoglobin,platelet and albumin were significantly decreased after surgery(P<0.05).In the groups of different surgical methods,the levels of blood glucose and D-dimer after surgery were higher than before surgery,and albumin was lower than before surgery(P<0.05).There were no significant differences in hemoglobin and bilirubin in pure IRE group before and after surgery(P>0.05),but the level of transaminase was increased after surgery(P<0.05),and the level of platelet was significantly decreased after surgery(P<0.05).There were no significant differences in hemoglobin,platelet and bilirubin in IRE+fluorouracil group before and after surgery(P>0.05),but the level of transaminase was increased after surgery(P<0.05).There were no significant differences in platelet and bilirubin IRE before and after operation in IRE+short-circuit operation group(P>0.05),while hemoglobin content was significantly decreased after operation(P<0.05).There were no significant differences in hemoglobin,platelet and bilirubin IRE before and after operation in IRE+fluorouracil+short-circuit operation group(P>0.05).The level of transaminase in the first two groups was significantly higher after surgery than before surgery,but not in the second two groups combined with short-circuit surgery(P>0.05).3.There were no significant differences among the four groups in terms of total hospital stay,postoperative hospital stay and intraoperative blood loss(P>0.05),but there were differences in the length of operation(P=0.001).The operation time of IRE+short-circuit operation group was longer than that of simple IRE group(P=0.003),and that of IRE+fluorouracil+short-circuit operation group was longer than that of simple IRE group(P=0.007).4.In all 33 patients with pancreatic cancer who underwent IRE ablation,the in-hospital mortality rate was 0,of which 25 patients(75.76%)had postoperative complications,14 had gradeⅠcomplications,7 had gradeⅡcomplications,2 had gradeⅢcomplications,and 2 had gradeⅣcomplications.Most of the complications were mild and improved after symptomatic treatment.The occurrence of complications was not related to the specific surgical method(P=0.09).There was no correlation between short-circuit operation and complication(P=0.493).5.There was no significant change in CA19-9 before and after surgery in all 33patients(P=0.053),and CA19-9 in IRE+fluorouracil group after surgery was decreased compared with that before surgery(P=0.017),but there was no significant change in CA19-9 before and after surgery in other groups(P>0.05).In order to further explore the effectiveness of IRE in the treatment of pancreatic cancer,the survival time of pancreatic cancer patients who received IRE alone without adjuvant therapy(23 cases)was compared with those who received radiotherapy(5 cases)and radiotherapy+chemotherapy(17 cases).The median survival OS of pancreatic cancer patients treated with IRE alone was 4.0 months and that of radiotherapy patients was 6.4 months,showing no significant difference(P=0.421).Compared with the median OS of 10.0 months in patients with pancreatic cancer treated with radiotherapy and chemotherapy,the survival of patients with pancreatic cancer treated with radiotherapy and chemotherapy was longer(P=0.002).6.Among 33 pancreatic cancer patients treated with IRE,31 died and 2 survived by March 2023.All patients were divided into IRE group alone(23 cases)and IRE+adjuvant therapy group(10 cases).The median OS was 4 months in the IRE group alone and 12 months in the IRE+adjuvant group.The survival of patients in the IRE+adjuvant group was longer than that in the IRE group alone(P<0.001).The median OS of IRE+adjuvant therapy group was 12 months,and the median OS of radiotherapy+chemotherapy group was 10 months.The survival of IRE+adjuvant therapy group was longer than that of radiotherapy+chemotherapy group(P=0.04).Univariate analysis found that patients’OS was related to treatment style(P<0.001)and tumor volume(P=0.009),and multivariate Cox regression analysis found that treatment style was an independent risk factor for patients’OS(P=0.001).Conclusion:This study confirmed that IRE is safe and feasible in the treatment of unresectable pancreatic cancer.IRE has been shown to be effective in treating pancreatic cancer compared with radiotherapy.This study observed a high incidence of complications after pancreatic IRE ablation,but most of them were minor complications,so further research is needed on how to develop pancreatic IRE to reduce the occurrence of complications.In addition,this study found that IRE combined with adjuvant therapy such as chemoradiotherapy,targeted therapy and immunotherapy can significantly prolong the survival time of pancreatic cancer patients,providing clinical basis for the comprehensive treatment of pancreatic cancer. |
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