| Background:Ultrasound-guided radiofrequency ablation(RFA)has become one of the main treatments for liver tumor <3cm because its high treatment efficacy and low complication risk.However,with the tumor size increases,the completely ablation rate decreased significantly.Tumor's uncompletely ablation was one of the main risk factors for overall survival.In 1996,Goldberg.S N discovered the blood flow inside or around the tumor can quickly take away the heat during RFA therapy and limit the expansion of the ablation lesion.This phenomenon is called the “Heat sink effect” and has been limitating the explasion of ablation zone.Assume performing RFA while blocking liver blood flow,it is possible to limit the heat sink effect and expand the ablation area,there by increasing the tumor complete ablation ratio.Hepatocellular carcinoma is mainly supplied by the hepatic artery,blocking hepatic artery combined with radiofrequency ablation can effectively reduce the heat sink effect and improve the radiofrequency ablation efficiency of liver cancer.But for the large tumor,the blood supply from the portal vein is rich and the surrounding satellite nodule is also located in the portal vein blood supply area.Blocking hepatic artery alone can't reduce the heat sink effect of the corresponding area thus achieve a dissatisfactory ablation zone.A study in Radiology confirmed that combine RFA with blocking portal or hepatic venous blood flow temporarily can reduced the in-situ recurrence rate to 11% of the liver tumor which is <35mm and adjacent to blood vessels >4mm,and the recurrence rate reported before was 53%.The validity of portal vein occlusion combined with RFA was initially confirmed.However,due to the lack of related research,the conclusion still needs further study to establish it.An in vitro study has confirmed that when the blood flow rate near the ablation site exceeds 5 ml/min,a strong heat sink effect can be caused.Therefore,there is a theoretical difference between total blockage of hepatic blood flow with single blockade of hepatic artery or portal vein blood flow on radiofrequency ablation.Therefore,we establish this experiment to observe the impact of different hepatic blood flow blocking methods on the liver ablation in a rabbit model.It may provide some help for the treatment of liver cancer which combine radiofrequency ablation with liver blood flow occlusion method.Because of the large-scale liver infarction after the separation of rabbit hepatic artery in animal experiments,we don't set the hepatic artery blocking group.Now Transcatheter arterial chemoembolization(TACE)has been widely used on inoperable liver cancer patients.When implementing TACE,the hepatic artery blood supply is blocked.In theory,the heat sink effect can be greatly reduced,there by increasing the ablation volume and improving the efficacy of RFA.However,many patients would get a rich collateral circulation after TACE,the incidence increases when patients receive two or more treatments.So the effect of TACE to RFA still needs further study.The study about whether TACE combined RFA can improve the overall survival than RFA alone for treating liver cancer are quitely different,especially when the tumor is <5cm.When should we replace RFA with TACE combined RFA is still unknow.Many clinical trials have small sample size,it limite the credibility of study conclusion.To clearify the effect of hepatic artery occlusion on RFA,our study intends to collect all the published clinical randomized controlled trial about comparing the TACE plus RFA with RFA for treating liver cancer,and conduct Meta-analysis to solve this problem.Objectives:1.To evaluate the impact of vascular occlusion of hepatic flow on radiofrequency ablation in rabbit model.2.To clearify whether TACE combined with RFA is effective or not in treating liver cancer with RFA alone by conducting Meta-analysis.Experiment 1: Materials and Methods:1.Experimental material(1)Experimental animal: 42 rabbits were divided into RFA group(NO group)randomly,portal vein occlusion + RFA group(PV group),both hepatic artery and portal vein occlusion+ RFA group(HA+PV group).(2)Experimental apparatus:Radiofrequency ablation system: RITA1500 system(RITA,USA),monopolar electrode divice with 10 cm,18-gauge cannulas and 5 mm treating tip(RITA,USA).VINNO diagnostic ultrasound system: VINNO70(VINNO Technology Co,Ltd.Suzhou,China)equipped with 9L linear array transducer(frequency range: 4-12MHz).2.Experimental procedure42 rabbits was assigned randomly to one of three groups,no occlusion(NO group),portal vein occlusion(PV group),both hepatic artery and portal vein occlusion(HA+PV group),n=14.Radiofrequency lesions were created in vivo using RITA 1500 system with cool tip radiofrequency electrode,the parameters were set at 80?,output at 15 W for 60 seconds.Implement different treatment to the liver vessel according to the grouping.After the hepatic blood flow status reached the expected protocol under colorful Doppler ultrasonography supervise,the radiofrequency ablation was then performed under real-time ultrasonography guidance.Using the Contrast-enhanced ultrasound(CEUS)to observe the morphology of the lesion and measure the size in three dimensions after 24 h,then sacrifice the animals,find the biggest tangent plain of ablation zone in CEUS under B model ultrasonography guidance and cut the lesion out along this area,then measure the size of the ablation lesion.Take the atrial blood of three rabbits each group and test the Alanine transaminase(ALT),Aspartate transaminase(AST),Gamma Gluamyltransferase(GGT),Alkaline phosphatase(ALP)in five time points(before therapy,and 1,3,5,7 days after therapy).Results:1.There are statistical differences between three groups in the size of ablation zone no matter under the CEUS or the gross specimen measurement,the ablation zone of the HA+PV group was the largest.2.The blood level of ALT,AST raised after RFA treatment and get the peak value 1 day after therapy,then declined slowly.They almost back to the baseline 1 week later.There is no significant difference in AST,ALT,ALP,GGT test between different groups.Conclusion:1.The vascular occlusion of hepatic inflow combined radiofrequency ablation can enhance the efficiency of radiofrequency ablation especially when completely block the hepatic blood inflow.2.Blocking hepatic blood flow combined RFA compared with RFA monotherapy did not cause severe liver damage and bile duct injury.Experiment 2: Methods:Search Pubmed,Cochrane library,Embase database,China National Knowledge Infrastructure and China Biology Medicine disc to collect studys from 2000 to 2018 according to a scheduled searching protocal.The randomized controlled clinical trials(RCT)comparing the therapeutic effect on hepatocellular carcinoma of TACE combined RFA with RFA were included.Collecting clinical studies according to the inclusion and exclusion criteria.Using the Cochrane systematic review table to evaluate the quality of the studys.Direct Meta-analysis was performed using Revman 5.3 software to compare the efficacy of the combination of TACE and RFA with RFA monotherapy.The experimental group was TACE combined RFA,and the control group was RFA monotherapy.The outcome indicators were 1,3-year overall survival rate(OS)and severe complication rate,which expressed as odds ratio(OR)and 95% confidence interval(CI).Results:1.8 RCTs were included after screening,with a total number of 753 patients,5 of them were RCTs about TACE combined with RFA versus RFA with liver tumor size <5 cm,including 467 patients.2.Comparison of TACE combined with RFA and RFA alone without considering the size of tumorFor 1 year overall survial rate,the Meta analysis showed :OR=2.27,CI=[1.40-3.69],P<0.05;For 3 year overall survial: OR=1.94,CI= [1.41-2.67],P<0.05;The Meta analysis shows TACE combined RFA can improve the 1,3-year overall survival comparing with RFA alone.For the severe complication incidence,OR=1.17,CI= [0.39,3.55],P>0.05,there is no statistical difference between TACE combined RFA with RFA alone in severe complication occurance.3.When the maximum liver tumor size is <5cm,the 1 year overall survial:OR=2.44,CI= [1.18,5.04],P<0.05;For 3 year overall survial:OR=2.11,CI= [1.41,3.15],P<0.05.The combination of TACE and RFA can significantly improve 1,3-year overall survival compared with RFA alone when the maximum tumor size is <5cm.Conclusion:The Meta-analysis indicates that1.TACE combined RFA can improve the1,3 year overall survival compared with RFA alone for people with liver cancer.2.when the maximum tumor size is <5cm,TACE combined RFA can improve the1,3 year overall survival compared with RFA alone. |
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