The Study Of Dose-effect Relationship On Increasing Radiofrequency Abalation Coagulation Zone By Acetic Acid Hypertonic Saline Solution Local Injection In Liver

1.backgroundPrimary hepatocellular carcinoma(HCC) is one of the most common tumors globally, scecondary HCC is also common tumor.Despite many therapies advance in the field of HCC over the past two decades,this disease continues to be a major cause of cancer-related mortality worldwide.Although being a promising treatment for early small HCC,the use of liver transplantation is limited due to shortage of donor organs and other reasons.Surgical resection of HCC is still the mainstream method in the radical therapy of HCC,but less than 30%of patients with HCC are operative candidates because of tumor size and other reasons.As a result,for patients with irresectable HCC,great attention has been payed to Percutaneous local ablative therapies,such as percutaneous ethanol injection(PEI), percutaneous acetic acid injection(PAl),radiofrequency ablation(RFA),cryoablation therapy(CST),microwave coagulation therapy(MCT),interstitial laser photocoagulation (ILP),trsanscatheter arterial chemoembolization(TACE) and so on.Among those local ablative therapies,RFA is the most widely used for irresectable HCC because of its minimal invasiveness,safty,cost-effectiveness and little complication rate.At prensent,the coagulation zone of single RFA only reach 3.5～4.0cm.It is difficult to achieve complete necrosis during treatment for tumor with a diameter greater than 3.0 cm.For this reason, many studies focus on how to enlarge the single RFA coagulation zone in recent years.Perfusion-mediated cooling effect by vascular plays an important role in coagulation volume.Treating HCC with 50%acetic acid has been reported in lots of clinical studies. 50%acetic acid can result in small vascular occlusion by induceing thrombosis.It is hypothesized that PAI,when used in combination with RFA,should increase the coagulation zone because of reducing quantity of heat losting caused by perfusion-mediated cooling effect.Ahmed and Lee demonstrated such suppose.At the same period,many studies proved that hypertonic NaCl injection before RFA can enlarge coagulation volume obviously by raising ion concentration,reducing impedence and enhancing local tissue electric current.Based on previous studies,combining the merits of both hypertonic NaCl and 50%acetic acid,Lee made acetic acid hypertonic NaCl solution(AHS),which was latter proved to further increase the coagulation zone when injected into the liver prior to RFA.Despite the effective of AHS in increasing the single RFA coagulation zone,but nowdays the dose-effect relationship between RFA coagulation zone and injection volume of AHS has not yet been reported.2.ObjectivesThis study is to explore the dose-effect relationship between RFA coagulation zone and injection volume of 50%acetic acid 5%hypertonic saline solution in ex vivo bovine liver and in vivo dog liver treated with RFA after AHS injection respectively.The safety and effective volume of AHS will also been determined.We want to give some useful suggestion about enhancing clinical therapeutic efficacy of RFA.3.Methods and Results(1) RFAs were performed in bovine liver after injection different dose of 50%acetic acid 5%hypertonic saline solution in eleven groups(n=8).The relationship between different AHS injection volume and variance of the mean coagulation diameter was observed.The mean initial impedence,the mean ablation time and the instance about spillage from the injection site were also recorded.GroupⅠ:RFA alone;groupⅡto groupⅪ:RFA after AHS injection(the injection volume varies from lml to 10ml).Results: The coagulation zone after RFA alone looked like a flask,with the coagulation zone after RFA combined with AHS injection resembling a ball.The mean diameter of couglation zone and the mean ablation time were different significantly among 11 groups.There was no significant difference in the mean initial impedence within 11 groups.The regressive equation is Y=2.318+0.103X when 0ml≤X≤10ml(X is the dose of AHS,Y is the mean diameter of coagulation zone).RFA coagulation zone increased greatly when volume of AHS is less than 2ml;the increment of RFA coagulation zone becomed small when volume of AHS is between 2～7ml;the increment of RFA coagulation zone was even smaller When volume of AHS was more than 7ml.AHS spillage from the injection site occurred when X≥6ml. (2) RFAs were performed in dog liver after Ultrasound-guided RFA 50%acetic acid 5%hypertonic saline solution injection.The mean coagulation diameter,the mean initial impedence,the mean ablation time,complication,variance of hepatic function and pathology were recorded.Animals were randomized into 5 groups with 6 animals in each groups.GroupA:RFA immediately after 2ml of AHS injection;GroupB:RFA delayed five minutes after injection of 2ml AHS;GroupC:RFA immediately after 4ml of AHs injection; groupD:RFA delayed five minutes after injection of 4ml AHS;groupE:RFA immediately after 6ml of AHS injection.Results:The mean coagulation diameter are different significantly among groupA,groupC and groupE.The mean coagulation diameter of groupE is the largest among five groups.There is no significant difference in the mean coagulation diameter between groupD and groupE.The mean ablation time of groupE is the longest among five groups.There is no significant difference in the mean initial impedence within five groups.Variance of hepatic function are different significantly among five groups.HE staining show the lung and kidney have obviosly hyperemia and hemorrhage in dogs died within 24h.The livers do not show typical appearance of coagulation necrosis at the same time.In dogs died fourteenth days postoperatively,the terminal line between coagulation necrosis zone and normal liver tissue is clear and incomplete,fibro-envelope can be seen.Structure of vasculars is destructed obviously in coagulation zone,hemorrhage of different phase occurs in vasculars of fibro-envelope zone,the pin-necrosis presents in normal liver tissue close to coagulation zone.Reticulin fiber staining show obviously thrombus in above zones.Four dogs died in groupE within two weeks but no dog died in other groups.AHS spillage from the injection site occurred in five dogs of group E.4.ConclusionIncreased volume of AHS injection lead to an obvious enlarged coagulation zone of single RFA in ex vivo bovine liver.The AHS injectin volume and the mean diameter of coagulation zone are positively correlated to some extent.There is no significant difference in the mean coagulation diameter when volume of AHS is greater than 7ml,meanwhile, obvious AHS spillage from the injection site occurres.Volume of AHS injection and time of RFA performed have significant impact on coagulation zone in the experiment of dogs. RFA,when performed 5minutes after 4ml of AHS injection in dog liver,results in ideal coagulation zone.Spillage from the injection site can lead to severe complication,to which close attention must be payed when patients of HCC undergo RFA in combination with AHS injection.More impotantly,the volume of AHS injection should be chosen cautiously.