Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper...Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.展开更多
Pancreatic cancer is currently the seventh leading cause of cancer death(4.5%of all cancer deaths)while 80%-90%of the patients suffer from unresectable disease at the time of diagnosis.Prognosis remains poor,with a me...Pancreatic cancer is currently the seventh leading cause of cancer death(4.5%of all cancer deaths)while 80%-90%of the patients suffer from unresectable disease at the time of diagnosis.Prognosis remains poor,with a mean survival up to 15 mo following systemic chemotherapy.Loco-regional thermal ablative techniques are rarely implemented due to the increased risk of thermal injury to the adjacent structures,which can lead to severe adverse events.Irreversible electroporation,a promising novel non-thermal ablative modality,has been recently introduced in clinical practice for the management of inoperable pancreatic cancer as a safer and more effective loco-regional treatment option.Experimental and initial clinical data are optimistic.This review will focus on the basic principles of IRE technology,currently available data,and future directions.展开更多
Irreversible electroporation(IRE) employs the use of an electric field to cause irreversible permeability of the cell membrane, inducing apoptosis. The use of IRE for locally advanced pancreatic cancer(LAPC) was first...Irreversible electroporation(IRE) employs the use of an electric field to cause irreversible permeability of the cell membrane, inducing apoptosis. The use of IRE for locally advanced pancreatic cancer(LAPC) was first described in 2012. The crucial advantage of IRE compared with other devices employing thermal ablation is the safety around vital structures such as vessels and ducts. This makes it an attractive option for use in the pancreas due to the close proximity of multiple major vascular structures, biliary ducts, and adjacent gastrointestinal organs. Over the past decade, IRE has established itself as a useful treatment adjunct and may soon become the standard of care, particularly for LAPC. This article will explore the current evidence and provide a concise summary of pertinent issues, including patient selection, preoperative management, clinical outcomes, radiological response and future prospects of IRE in pancreatic cancer.展开更多
Background: Irreversible electroporation(IRE) is a novel ablative technique for hepatobiliary and pancreatic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepato...Background: Irreversible electroporation(IRE) is a novel ablative technique for hepatobiliary and pancreatic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepatobiliary and pancreatic cancers. Data sources: Studies were identified by searching Pub Med and Embase for articles published in English from database inception through July 31, 2017. For inclusion, each clinical study had to report morbidity and survival data on hepatobiliary and pancreatic cancers treated with IRE and contain at least 10 patients. Studies that met these criteria were included for analysis. Two authors assessed each clinical study for data extraction. The controversial parts were resolved through discussion with seniors. Results: A total of 24 clinical studies were included. Fourteen focused on hepatic ablation with IRE comprising 437 patients with 666 lesions of different tumor types. Two patients(0.5%) died after the IRE procedure. Morbidity of hepatic ablation with IRE ranged from 7% to 35%. Most complications were mild. Complete response for hepatic tumors was reported as 57%–97%. Ten studies with 455 patients focused on pancreatic IRE. The overall mortality of IRE in pancreatic cancer was 2%. Overall severe morbidity of IRE in pancreatic cancer ranged from 0 to 20%. The median overall survival after IRE ranged from 7 to 23 months. Patients treated with IRE combined with surgical resection showed a longer overall survival. Conclusions: IRE significantly improves the prognosis of advanced hepatobiliary and pancreatic malignances, and companied with less complications. Hence, IRE is a relatively safe and effective non-thermal ablation strategy and potentially recommended as an option for therapy of patients with hepatobiliary and pancreatic malignances.展开更多
Portal vein thrombosis(PVT) is a rare but serious postoperative complication associated with irreversible electroporation(IRE). We report a case of postoperative PVT in a 54-year-old woman who underwent IRE for locall...Portal vein thrombosis(PVT) is a rare but serious postoperative complication associated with irreversible electroporation(IRE). We report a case of postoperative PVT in a 54-year-old woman who underwent IRE for locally advanced pancreatic cancer. Drain removal and discharge of the patient from the hospital were scheduled on postoperative day(POD) 7; however, a magnetic resonance imaging scan revealed the presence of PVT. We suspected postoperative inflammation in the pancreas as the main cause of PVT. However, the patient did not undergo any medical treatment because she did not have any clinical symptoms, and she was discharged on POD 8.展开更多
BACKGROUND Locally advanced pancreatic cancer(LAPC)is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world.The prognosis of LAPC is poor even after stan...BACKGROUND Locally advanced pancreatic cancer(LAPC)is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world.The prognosis of LAPC is poor even after standard treatment.Irreversible electroporation(IRE)is a novel ablative strategy for LAPC.Several studies have confirmed the safety of IRE.To date,no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine(GEM)plus concurrent IRE.AIM To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC.METHODS From February 2016 to September 2017,a total of 68 LAPC patients were treated with GEM plus concurrent IRE(n=33)or GEM alone(n=35).Overall survival(OS),progression free survival(PFS),and procedure-related complications were compared between the two groups.Multivariate analyses were performed to identify any prognostic factors.RESULTS There were no treatment-related deaths.The technical success rate of IRE ablation was 100%.The GEM+IRE group had a significantly longer OS from the time of diagnosis of LAPC(19.8 mo vs 9.3 mo,P<0.0001)than the GEM alone group.The GEM+IRE group had a significantly longer PFS(8.3 mo vs 4.7 mo,P<0.0001)than the GEM alone group.Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS.CONCLUSION Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.展开更多
Irreversible electroporation(IRE) is a non-thermal ablation technique used especially in locally advanced pancreatic carcinomas that are considered surgically unresectable.We present the first case of acute superior m...Irreversible electroporation(IRE) is a non-thermal ablation technique used especially in locally advanced pancreatic carcinomas that are considered surgically unresectable.We present the first case of acute superior mesenteric artery(SMA) occlusion secondary to pancreatic IRE procedure that has not been reported before in the literature.A 66-year-old man underwent neoadjuvant chemoradiotherapy for locally advanced pancreatic ductal adenocarcinoma.IRE procedure was applied to the patient during laparotomy under general anesthesia.After finishing the procedure,an acute intestinal ischemia was detected.A conventional vascular angiography was performed and a metallic stent was successfully placed to the SMA and blood flow was maintained.It is important to be careful in such cases of tumor involvement of SMA when evaluating for IRE procedure of pancreatic tumor.展开更多
BACKGROUND Irreversible electroporation(IRE)is a local non-thermal ablative technique which has been suggested as a potential cancer therapy.However,the specific anatomic characteristics of the pancreatic head make it...BACKGROUND Irreversible electroporation(IRE)is a local non-thermal ablative technique which has been suggested as a potential cancer therapy.However,the specific anatomic characteristics of the pancreatic head make it challenging to perform any local ablation in this region.Therefore,the safety and feasibility of IRE in the pancreatic head region should be further explored.AIM To evaluate the safety of IRE in pancreatic head region including its effects on pancreatic ducts,vessels,and adjacent gastrointestinal organs.METHODS Eight landrace miniature pigs underwent IRE of pancreatic head tissue successfully,with a total of 16 lesions created.Laboratory testing including white blood cell(WBC)count and serum amylase before IRE with follow-up laboratory analysis and pathological examination at 1,7,14,and 28 d postablation were performed.RESULTS All pigs tolerated the ablation procedure without serious perioperative complications.Transiently elevated WBC count and amylase were observed at 24 h post-IRE,suggesting an acute pancreatic tissue damage which was confirmed by pathological observations.Vascular endothelial cells and pancreatic duct epithelial cells in ablation zone were also positive in terminal deoxynucleotidyl transferase dUTP nick end labeling staining.There was extensive duodenum mucosa damage with local hemorrhage 24 h after ablation,while regeneration of new villous structures were observed at 7 and 28 d post-IRE.Masson’s trichromatic staining showed that the extracellular matrix was still intact in vessels and pancreatic ducts,and even in the duodenum.CONCLUSION IRE ablation to the pancreatic head may be safe and feasible without long-term damage to the surrounding vital structures.However,risks of stress injuries in acute phase should be taken into consideration to prevent severe perioperative complications.展开更多
BACKGROUND Pancreatic cancer has a poor prognosis;40%–50% of patients have liver metastases at the time of initial diagnosis and only 15%–20% undergo surgical resection. Irreversible electroporation(IRE) is a new, n...BACKGROUND Pancreatic cancer has a poor prognosis;40%–50% of patients have liver metastases at the time of initial diagnosis and only 15%–20% undergo surgical resection. Irreversible electroporation(IRE) is a new, non-thermal local ablation method for solid tumors, which can induce cell membrane permeabilization,resulting in unrecoverable nanoscale perforation and apoptotic cell death without damaging the structural components of tissues.CASE SUMMARY We report the case of a 66-year-old female patient with liver metastasis from pancreatic cancer with a pathological diagnosis of poorly differentiated adenocarcinoma. Carbohydrate antigen 19-9 was elevated to 420.3 U/m L.Computed tomography showed a pancreas mass of 2.7 cm × 2.5 cm and single liver metastasis of 1.4 cm × 1.1 cm in the S6 area. The patient underwent IRE and arterial infusion chemotherapy and received tegafur. The therapeutic effect of the combination treatment has been evaluated as complete response. To date, the patient has survived for > 12 mo and is receiving tegafur as maintenance therapy(at the time this case report was written).CONCLUSION IRE plus arterial infusion chemotherapy and tegafur may be synergistic,providing a reference for treating liver metastasis from pancreatic cancer.展开更多
Objective:Irreversible electroporation(IRE)is a nonthermal ablation technique for the treatment of malignant liver tumors.IRE has demonstrated efficacy and safety in the treatment of malignant liver tumors and its uni...Objective:Irreversible electroporation(IRE)is a nonthermal ablation technique for the treatment of malignant liver tumors.IRE has demonstrated efficacy and safety in the treatment of malignant liver tumors and its unique advantages in the treatment of nearby vascular lesions.This study aimed to compare the efficacy,safety,and intermediate-term outcomes of IRE and radiofrequency(RF)therapy in malignant liver tumors.Methods:Twenty-four patients with primary or secondary liver malignancies were included in this prospective,double-arm clinical trial.Patients were randomly divided into the IRE and RF groups.The primary outcome was the efficacy(local ablation control evaluation at 90 days).The secondary outcomes were safety(procedure-related complications at≤90 days)and intermediate-term survival(at 24 months).Results:The ablation assessment at 90 days after surgery with m RECIST for IRE versus RF were 70%,20%,0%,and 10%versus 92.9%,7.1%,0%,and 0%(CR,PR,SD,and PD,respectively).The complication rates of IRE versus RF with Clavien-Dindo classification were 16.7%,25%,0%,8.3%,and 8.3%versus 8.3%,50%,0%,0%,and 0%(Grade I,II,Ⅲ,IV,and V,respectively).The average overall survival(OS)was 17.55 months in the IRE group(95%CI 15.13-22.37)and 18.75 months in the RF group(95%CI 12.48-22.61).There was no statistical difference between the IRE and RF groups in terms of efficacy(p=0.48),safety(p=0.887),or 24-month OS(p=0.959).Conclusions:IRE ablation revealed similar efficacy and safety in a short-term follow-up,and similar OS in midterm survival as RF ablation in treating malignant hepatic tumors.展开更多
Objectives:To preliminarily evaluate the clinical effectiveness and safety of computed tomography(CT)imageguided irreversible electroporation(IRE)for the treatment of recurrent hepatocellular carcinoma(HCC)after surgi...Objectives:To preliminarily evaluate the clinical effectiveness and safety of computed tomography(CT)imageguided irreversible electroporation(IRE)for the treatment of recurrent hepatocellular carcinoma(HCC)after surgical resection.Methods:From January 2016 to February 2018,18 patients diagnosed with recurrent HCC after surgical resection received IRE under CT image guidance for 22 tumors.Patients were enrolled for IRE when ineligible for thermal ablation due to tumor location.Clinical records and imaging data were reviewed to assess complete ablation rate,local tumor progression free rate(LTPFR),local tumor progression free survival(LTPFS)and complications after a median follow-up time of 14 months.Results:Successful complete ablations were achieved in 20/22(90.1%)tumors.Mean LTPFS was 10.5?9.4 months.Overall 3-,6-and 12-months LTPFR in 22 tumors following IRE were 68.2%(95%confidence interval[CI]:45%–83%),59.1%(95%CI:33%–76%)and 36.4%(95%CI:17%–56%),respectively.Complications included pneumothorax(2/18,11.1%),localized pain(3/18,16.7%),bile duct dilation(1/18,5.6%)and transient hypertension(1/18,5.6%).No major complications or treatment-related deaths were observed.The alphafetoprotein levels of two patients decreased to the normal range at 3 and 4 months,respectively.Conclusions:This study showed that percutaneous CT image-guided IRE can serve as a safe and effective treatment for recurrent HCC not suitable for thermal ablation.展开更多
AIM To determine changes in the morphology and function of pancreatic cancer cells after irreversible electroporation(IRE) treatment, and to explore the clinical significance of IRE treatment for pancreatic cancer pro...AIM To determine changes in the morphology and function of pancreatic cancer cells after irreversible electroporation(IRE) treatment, and to explore the clinical significance of IRE treatment for pancreatic cancer providing an experimental basis for the clinical application of IRE treatment. METHODS IRE was carried out in an athymic nude mouse model of pancreatic carcinoma generated with human pancreatic cancer cells 1. In therapy groups, IRE electrodes were inserted with 90 pulses per second at 800 V/cm applied to ablate the targeted tumor tissues. Histological assessment of the affected tissue was performed by hematoxylin and eosin staining(HE). Quantification of cell proliferation and apoptosis was performed by evaluating Ki67 and caspase-3 levels, respectively. Flow cytometry was used to assess cell apoptosis. Ultrasound imaging was carried out to evaluate IRE treatment results. Pathological correlation studies showed IRE is effective for the targeted ablation of pancreatic tumors in an orthotopic mouse model.RESULTS IRE was efficacious in removing tumors in the orthotopic mouse model. The IRE-ablated zone displays characteristics of nude mouse models at different time-points as assessed by hematoxylin and eosin staining. Immunohistochemical analysis of samples from the pancreatic cancer models showed significantly enhanced caspase-3 cleavage and Ki67. Flow cytometry data corroborated the above findings that apoptosis in tumor cells was observed immediately on the first postoperative day, and with time the middle and late stages of apoptosis were observed. For ultrasound imaging studies, the IRE ablation zone became a hyperechoic area due to increasing inflammatory and immunologic cellular contents. CONCLUSION IRE is a promising new approach for pancreatic cancer, with many potential advantages over conventional ablation techniques.展开更多
BACKGROUND In the first studies of electrochemotherapy(ECT),small cutaneous metastases were treated and only mild or moderate pain was observed;therefore,pain was not considered a significant issue.As the procedure be...BACKGROUND In the first studies of electrochemotherapy(ECT),small cutaneous metastases were treated and only mild or moderate pain was observed;therefore,pain was not considered a significant issue.As the procedure began to be applied to larger cutaneous metastases,pain was reported more frequently.For that reason,reduction of both muscle contractions and pain have been investigated over the years.AIM To present an overview of different protocols described in literature that aim to reduce muscle contractions and pain caused by the electroporation(EP)effect in both ECT and irreversible EP treatments.METHODS Thirty-three studies published between January 1999 and November 2020 were included.Different protocol designs and electrode geometries that reduce patient pain and the number of muscle contractions and their intensity were analysed.RESULTS The analysis showed that both high frequency and bipolar/biphasic pulses can be used to reduce pain and muscle contractions in patients who undergo EP treatments.Moreover,adequate electrode design can decrease EP-related morbidity.Particularly,needle length,diameter and configuration of the distance between the needles can be optimised so that the muscle volume crossed by the current is reduced as much as possible.Bipolar/biphasic pulses with an inadequate pulse length seem to have a less evident effect on the membrane permeability compared with the standard pulse protocol.For that reason,the number of pulses and the voltage amplitude,as well as the pulse duration and frequency,must be chosen so that the dose of delivered energy guarantees EP efficacy.CONCLUSION Pain reduction in EP-based treatments can be achieved by appropriately defining the protocol parameters and electrode design.Most results can be achieved with high frequency and/or bipolar/biphasic pulses.However,the efficacy of these alternative protocols remains a crucial point to be assessed further.展开更多
Background： Locally advanced pancreatic carcinoma （LAPC） is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation （IRE） has emerged as a potential option f...Background： Locally advanced pancreatic carcinoma （LAPC） is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation （IRE） has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC. Methods： Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE. Results： All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed （16%）： two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge. Conclusions： IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy.展开更多
Background:High-frequency irreversible electroporation(H-FIRE)is a novel,next-generation nanoknife technology with the advantage of relieving irreversible electroporation(IRE)-induced muscle contractions.However,the d...Background:High-frequency irreversible electroporation(H-FIRE)is a novel,next-generation nanoknife technology with the advantage of relieving irreversible electroporation(IRE)-induced muscle contractions.However,the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined.This study aimed to compare the efficacy of the two treatments in vivo.Methods:Ten Bamaminiature swinewere divided into two group:five in the 1-day group and five in the 7-day group.The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant(Krans),rate constant(Kep)and extravascular extracellular volume fraction(Ve)value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),size of the ablation zone,and histologic analysis.Each animal underwent the IRE andH-FIRE.Temperatures of the electrodesweremeasured during ablation.DCE-MRI images were obtained 1,4,and 7 days after ablation in the 7-day group.All animals in the two groups were euthanized 1 day or 7 days after ablation,and subsequently,IRE and H-FIRE treated liver tissues were collected for histological examination.Student’s t test or Mann-Whitney U test was applied for comparing any two groups.One-way analysis of variance(ANOVA)test and Welch’s ANOVA test followed byHolm-Sidak’smultiple comparisons test,one-wayANOVAwith repeatedmeasures followed by Bonferroni test,or Kruskal-Wallis H test followed by Dunn’s multiple comparison test was used for multiple group comparisons and post hoc analyses.Pearson correlation coefficient test was conducted to analyze the relationship between two variables.Results:Higher Ve was seen in IRE zone than in H-FIRE zone(0.14±0.02 vs.0.08±0.05,t=2.408,P=0.043)on day 4,but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points(all P>0.05).For IRE zone,the greatest Ktrans was seen on day 7,which was significantly higher than that on day 1(P=0.033).The ablation zone size of H-FIRE was significantly larger than IRE 1 day(4.74±0.88 cm^(2)vs.3.20±0.77 cm^(2),t=3.241,P=0.009)and 4 days(2.22±0.83 cm^(2)vs.1.30±0.50 cm^(2),t=2.343,P=0.041)after treatment.Apoptotic index(0.05±0.02 vs.0.73±0.06 vs.0.68±0.07,F=241.300,P<0.001)and heat shock protein 70(HSP70)(0.03±0.01 vs.0.46±0.09 vs.and 0.42±0.07,F=64.490,P<0.001)were significantly different between the untreated,IRE and H-FIRE zones,but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone(both P>0.05).Electrode temperature variations were not significantly different between the two zones(18.00±3.77℃ vs.16.20±7.45℃,t=0.682,P=0.504).The Ktrans value(r=0.940,P=0.017)and the Kep value(r=0.895,P=0.040)of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.Conclusions:H-FIRE showed a comparable ablation effect to IRE.DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.展开更多
基金Supported by Department of Biotechnology,Government of India,No.RLS/BT/Re-entry/05/2012.
文摘Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.
文摘Pancreatic cancer is currently the seventh leading cause of cancer death(4.5%of all cancer deaths)while 80%-90%of the patients suffer from unresectable disease at the time of diagnosis.Prognosis remains poor,with a mean survival up to 15 mo following systemic chemotherapy.Loco-regional thermal ablative techniques are rarely implemented due to the increased risk of thermal injury to the adjacent structures,which can lead to severe adverse events.Irreversible electroporation,a promising novel non-thermal ablative modality,has been recently introduced in clinical practice for the management of inoperable pancreatic cancer as a safer and more effective loco-regional treatment option.Experimental and initial clinical data are optimistic.This review will focus on the basic principles of IRE technology,currently available data,and future directions.
文摘Irreversible electroporation(IRE) employs the use of an electric field to cause irreversible permeability of the cell membrane, inducing apoptosis. The use of IRE for locally advanced pancreatic cancer(LAPC) was first described in 2012. The crucial advantage of IRE compared with other devices employing thermal ablation is the safety around vital structures such as vessels and ducts. This makes it an attractive option for use in the pancreas due to the close proximity of multiple major vascular structures, biliary ducts, and adjacent gastrointestinal organs. Over the past decade, IRE has established itself as a useful treatment adjunct and may soon become the standard of care, particularly for LAPC. This article will explore the current evidence and provide a concise summary of pertinent issues, including patient selection, preoperative management, clinical outcomes, radiological response and future prospects of IRE in pancreatic cancer.
基金supported by grants from the Traditional Chinese Medicine Scientific Research Fund Project of Zhejiang province(No.2017ZA079)the Key Research Development Program of Zhejiang province(No.2018C03018)+1 种基金the Key Science and Tech-nology Program of Zhejiang Provience(No.WKJ-ZJ-1923)the National S&T Major Project of China(No.2018ZX10301201)
文摘Background: Irreversible electroporation(IRE) is a novel ablative technique for hepatobiliary and pancreatic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepatobiliary and pancreatic cancers. Data sources: Studies were identified by searching Pub Med and Embase for articles published in English from database inception through July 31, 2017. For inclusion, each clinical study had to report morbidity and survival data on hepatobiliary and pancreatic cancers treated with IRE and contain at least 10 patients. Studies that met these criteria were included for analysis. Two authors assessed each clinical study for data extraction. The controversial parts were resolved through discussion with seniors. Results: A total of 24 clinical studies were included. Fourteen focused on hepatic ablation with IRE comprising 437 patients with 666 lesions of different tumor types. Two patients(0.5%) died after the IRE procedure. Morbidity of hepatic ablation with IRE ranged from 7% to 35%. Most complications were mild. Complete response for hepatic tumors was reported as 57%–97%. Ten studies with 455 patients focused on pancreatic IRE. The overall mortality of IRE in pancreatic cancer was 2%. Overall severe morbidity of IRE in pancreatic cancer ranged from 0 to 20%. The median overall survival after IRE ranged from 7 to 23 months. Patients treated with IRE combined with surgical resection showed a longer overall survival. Conclusions: IRE significantly improves the prognosis of advanced hepatobiliary and pancreatic malignances, and companied with less complications. Hence, IRE is a relatively safe and effective non-thermal ablation strategy and potentially recommended as an option for therapy of patients with hepatobiliary and pancreatic malignances.
文摘Portal vein thrombosis(PVT) is a rare but serious postoperative complication associated with irreversible electroporation(IRE). We report a case of postoperative PVT in a 54-year-old woman who underwent IRE for locally advanced pancreatic cancer. Drain removal and discharge of the patient from the hospital were scheduled on postoperative day(POD) 7; however, a magnetic resonance imaging scan revealed the presence of PVT. We suspected postoperative inflammation in the pancreas as the main cause of PVT. However, the patient did not undergo any medical treatment because she did not have any clinical symptoms, and she was discharged on POD 8.
基金Supported by International Science Foundation of Affiliated Fuda Cancer Hospital,Jinan University,No.Y2018-ZD-01.
文摘BACKGROUND Locally advanced pancreatic cancer(LAPC)is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world.The prognosis of LAPC is poor even after standard treatment.Irreversible electroporation(IRE)is a novel ablative strategy for LAPC.Several studies have confirmed the safety of IRE.To date,no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine(GEM)plus concurrent IRE.AIM To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC.METHODS From February 2016 to September 2017,a total of 68 LAPC patients were treated with GEM plus concurrent IRE(n=33)or GEM alone(n=35).Overall survival(OS),progression free survival(PFS),and procedure-related complications were compared between the two groups.Multivariate analyses were performed to identify any prognostic factors.RESULTS There were no treatment-related deaths.The technical success rate of IRE ablation was 100%.The GEM+IRE group had a significantly longer OS from the time of diagnosis of LAPC(19.8 mo vs 9.3 mo,P<0.0001)than the GEM alone group.The GEM+IRE group had a significantly longer PFS(8.3 mo vs 4.7 mo,P<0.0001)than the GEM alone group.Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS.CONCLUSION Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.
文摘Irreversible electroporation(IRE) is a non-thermal ablation technique used especially in locally advanced pancreatic carcinomas that are considered surgically unresectable.We present the first case of acute superior mesenteric artery(SMA) occlusion secondary to pancreatic IRE procedure that has not been reported before in the literature.A 66-year-old man underwent neoadjuvant chemoradiotherapy for locally advanced pancreatic ductal adenocarcinoma.IRE procedure was applied to the patient during laparotomy under general anesthesia.After finishing the procedure,an acute intestinal ischemia was detected.A conventional vascular angiography was performed and a metallic stent was successfully placed to the SMA and blood flow was maintained.It is important to be careful in such cases of tumor involvement of SMA when evaluating for IRE procedure of pancreatic tumor.
文摘BACKGROUND Irreversible electroporation(IRE)is a local non-thermal ablative technique which has been suggested as a potential cancer therapy.However,the specific anatomic characteristics of the pancreatic head make it challenging to perform any local ablation in this region.Therefore,the safety and feasibility of IRE in the pancreatic head region should be further explored.AIM To evaluate the safety of IRE in pancreatic head region including its effects on pancreatic ducts,vessels,and adjacent gastrointestinal organs.METHODS Eight landrace miniature pigs underwent IRE of pancreatic head tissue successfully,with a total of 16 lesions created.Laboratory testing including white blood cell(WBC)count and serum amylase before IRE with follow-up laboratory analysis and pathological examination at 1,7,14,and 28 d postablation were performed.RESULTS All pigs tolerated the ablation procedure without serious perioperative complications.Transiently elevated WBC count and amylase were observed at 24 h post-IRE,suggesting an acute pancreatic tissue damage which was confirmed by pathological observations.Vascular endothelial cells and pancreatic duct epithelial cells in ablation zone were also positive in terminal deoxynucleotidyl transferase dUTP nick end labeling staining.There was extensive duodenum mucosa damage with local hemorrhage 24 h after ablation,while regeneration of new villous structures were observed at 7 and 28 d post-IRE.Masson’s trichromatic staining showed that the extracellular matrix was still intact in vessels and pancreatic ducts,and even in the duodenum.CONCLUSION IRE ablation to the pancreatic head may be safe and feasible without long-term damage to the surrounding vital structures.However,risks of stress injuries in acute phase should be taken into consideration to prevent severe perioperative complications.
文摘BACKGROUND Pancreatic cancer has a poor prognosis;40%–50% of patients have liver metastases at the time of initial diagnosis and only 15%–20% undergo surgical resection. Irreversible electroporation(IRE) is a new, non-thermal local ablation method for solid tumors, which can induce cell membrane permeabilization,resulting in unrecoverable nanoscale perforation and apoptotic cell death without damaging the structural components of tissues.CASE SUMMARY We report the case of a 66-year-old female patient with liver metastasis from pancreatic cancer with a pathological diagnosis of poorly differentiated adenocarcinoma. Carbohydrate antigen 19-9 was elevated to 420.3 U/m L.Computed tomography showed a pancreas mass of 2.7 cm × 2.5 cm and single liver metastasis of 1.4 cm × 1.1 cm in the S6 area. The patient underwent IRE and arterial infusion chemotherapy and received tegafur. The therapeutic effect of the combination treatment has been evaluated as complete response. To date, the patient has survived for > 12 mo and is receiving tegafur as maintenance therapy(at the time this case report was written).CONCLUSION IRE plus arterial infusion chemotherapy and tegafur may be synergistic,providing a reference for treating liver metastasis from pancreatic cancer.
文摘Objective:Irreversible electroporation(IRE)is a nonthermal ablation technique for the treatment of malignant liver tumors.IRE has demonstrated efficacy and safety in the treatment of malignant liver tumors and its unique advantages in the treatment of nearby vascular lesions.This study aimed to compare the efficacy,safety,and intermediate-term outcomes of IRE and radiofrequency(RF)therapy in malignant liver tumors.Methods:Twenty-four patients with primary or secondary liver malignancies were included in this prospective,double-arm clinical trial.Patients were randomly divided into the IRE and RF groups.The primary outcome was the efficacy(local ablation control evaluation at 90 days).The secondary outcomes were safety(procedure-related complications at≤90 days)and intermediate-term survival(at 24 months).Results:The ablation assessment at 90 days after surgery with m RECIST for IRE versus RF were 70%,20%,0%,and 10%versus 92.9%,7.1%,0%,and 0%(CR,PR,SD,and PD,respectively).The complication rates of IRE versus RF with Clavien-Dindo classification were 16.7%,25%,0%,8.3%,and 8.3%versus 8.3%,50%,0%,0%,and 0%(Grade I,II,Ⅲ,IV,and V,respectively).The average overall survival(OS)was 17.55 months in the IRE group(95%CI 15.13-22.37)and 18.75 months in the RF group(95%CI 12.48-22.61).There was no statistical difference between the IRE and RF groups in terms of efficacy(p=0.48),safety(p=0.887),or 24-month OS(p=0.959).Conclusions:IRE ablation revealed similar efficacy and safety in a short-term follow-up,and similar OS in midterm survival as RF ablation in treating malignant hepatic tumors.
文摘Objectives:To preliminarily evaluate the clinical effectiveness and safety of computed tomography(CT)imageguided irreversible electroporation(IRE)for the treatment of recurrent hepatocellular carcinoma(HCC)after surgical resection.Methods:From January 2016 to February 2018,18 patients diagnosed with recurrent HCC after surgical resection received IRE under CT image guidance for 22 tumors.Patients were enrolled for IRE when ineligible for thermal ablation due to tumor location.Clinical records and imaging data were reviewed to assess complete ablation rate,local tumor progression free rate(LTPFR),local tumor progression free survival(LTPFS)and complications after a median follow-up time of 14 months.Results:Successful complete ablations were achieved in 20/22(90.1%)tumors.Mean LTPFS was 10.5?9.4 months.Overall 3-,6-and 12-months LTPFR in 22 tumors following IRE were 68.2%(95%confidence interval[CI]:45%–83%),59.1%(95%CI:33%–76%)and 36.4%(95%CI:17%–56%),respectively.Complications included pneumothorax(2/18,11.1%),localized pain(3/18,16.7%),bile duct dilation(1/18,5.6%)and transient hypertension(1/18,5.6%).No major complications or treatment-related deaths were observed.The alphafetoprotein levels of two patients decreased to the normal range at 3 and 4 months,respectively.Conclusions:This study showed that percutaneous CT image-guided IRE can serve as a safe and effective treatment for recurrent HCC not suitable for thermal ablation.
文摘AIM To determine changes in the morphology and function of pancreatic cancer cells after irreversible electroporation(IRE) treatment, and to explore the clinical significance of IRE treatment for pancreatic cancer providing an experimental basis for the clinical application of IRE treatment. METHODS IRE was carried out in an athymic nude mouse model of pancreatic carcinoma generated with human pancreatic cancer cells 1. In therapy groups, IRE electrodes were inserted with 90 pulses per second at 800 V/cm applied to ablate the targeted tumor tissues. Histological assessment of the affected tissue was performed by hematoxylin and eosin staining(HE). Quantification of cell proliferation and apoptosis was performed by evaluating Ki67 and caspase-3 levels, respectively. Flow cytometry was used to assess cell apoptosis. Ultrasound imaging was carried out to evaluate IRE treatment results. Pathological correlation studies showed IRE is effective for the targeted ablation of pancreatic tumors in an orthotopic mouse model.RESULTS IRE was efficacious in removing tumors in the orthotopic mouse model. The IRE-ablated zone displays characteristics of nude mouse models at different time-points as assessed by hematoxylin and eosin staining. Immunohistochemical analysis of samples from the pancreatic cancer models showed significantly enhanced caspase-3 cleavage and Ki67. Flow cytometry data corroborated the above findings that apoptosis in tumor cells was observed immediately on the first postoperative day, and with time the middle and late stages of apoptosis were observed. For ultrasound imaging studies, the IRE ablation zone became a hyperechoic area due to increasing inflammatory and immunologic cellular contents. CONCLUSION IRE is a promising new approach for pancreatic cancer, with many potential advantages over conventional ablation techniques.
文摘BACKGROUND In the first studies of electrochemotherapy(ECT),small cutaneous metastases were treated and only mild or moderate pain was observed;therefore,pain was not considered a significant issue.As the procedure began to be applied to larger cutaneous metastases,pain was reported more frequently.For that reason,reduction of both muscle contractions and pain have been investigated over the years.AIM To present an overview of different protocols described in literature that aim to reduce muscle contractions and pain caused by the electroporation(EP)effect in both ECT and irreversible EP treatments.METHODS Thirty-three studies published between January 1999 and November 2020 were included.Different protocol designs and electrode geometries that reduce patient pain and the number of muscle contractions and their intensity were analysed.RESULTS The analysis showed that both high frequency and bipolar/biphasic pulses can be used to reduce pain and muscle contractions in patients who undergo EP treatments.Moreover,adequate electrode design can decrease EP-related morbidity.Particularly,needle length,diameter and configuration of the distance between the needles can be optimised so that the muscle volume crossed by the current is reduced as much as possible.Bipolar/biphasic pulses with an inadequate pulse length seem to have a less evident effect on the membrane permeability compared with the standard pulse protocol.For that reason,the number of pulses and the voltage amplitude,as well as the pulse duration and frequency,must be chosen so that the dose of delivered energy guarantees EP efficacy.CONCLUSION Pain reduction in EP-based treatments can be achieved by appropriately defining the protocol parameters and electrode design.Most results can be achieved with high frequency and/or bipolar/biphasic pulses.However,the efficacy of these alternative protocols remains a crucial point to be assessed further.
文摘Background： Locally advanced pancreatic carcinoma （LAPC） is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation （IRE） has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC. Methods： Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE. Results： All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed （16%）： two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge. Conclusions： IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy.
基金This work was supported by a grant from the National Natural Science Foundation of China(No.81771944).
文摘Background:High-frequency irreversible electroporation(H-FIRE)is a novel,next-generation nanoknife technology with the advantage of relieving irreversible electroporation(IRE)-induced muscle contractions.However,the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined.This study aimed to compare the efficacy of the two treatments in vivo.Methods:Ten Bamaminiature swinewere divided into two group:five in the 1-day group and five in the 7-day group.The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant(Krans),rate constant(Kep)and extravascular extracellular volume fraction(Ve)value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),size of the ablation zone,and histologic analysis.Each animal underwent the IRE andH-FIRE.Temperatures of the electrodesweremeasured during ablation.DCE-MRI images were obtained 1,4,and 7 days after ablation in the 7-day group.All animals in the two groups were euthanized 1 day or 7 days after ablation,and subsequently,IRE and H-FIRE treated liver tissues were collected for histological examination.Student’s t test or Mann-Whitney U test was applied for comparing any two groups.One-way analysis of variance(ANOVA)test and Welch’s ANOVA test followed byHolm-Sidak’smultiple comparisons test,one-wayANOVAwith repeatedmeasures followed by Bonferroni test,or Kruskal-Wallis H test followed by Dunn’s multiple comparison test was used for multiple group comparisons and post hoc analyses.Pearson correlation coefficient test was conducted to analyze the relationship between two variables.Results:Higher Ve was seen in IRE zone than in H-FIRE zone(0.14±0.02 vs.0.08±0.05,t=2.408,P=0.043)on day 4,but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points(all P>0.05).For IRE zone,the greatest Ktrans was seen on day 7,which was significantly higher than that on day 1(P=0.033).The ablation zone size of H-FIRE was significantly larger than IRE 1 day(4.74±0.88 cm^(2)vs.3.20±0.77 cm^(2),t=3.241,P=0.009)and 4 days(2.22±0.83 cm^(2)vs.1.30±0.50 cm^(2),t=2.343,P=0.041)after treatment.Apoptotic index(0.05±0.02 vs.0.73±0.06 vs.0.68±0.07,F=241.300,P<0.001)and heat shock protein 70(HSP70)(0.03±0.01 vs.0.46±0.09 vs.and 0.42±0.07,F=64.490,P<0.001)were significantly different between the untreated,IRE and H-FIRE zones,but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone(both P>0.05).Electrode temperature variations were not significantly different between the two zones(18.00±3.77℃ vs.16.20±7.45℃,t=0.682,P=0.504).The Ktrans value(r=0.940,P=0.017)and the Kep value(r=0.895,P=0.040)of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.Conclusions:H-FIRE showed a comparable ablation effect to IRE.DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.
