A Rct Study Of Laparoscopic Hepatectomy And Radiofrequency Ablation In The Treatment Of Recurrent Hepatocellular Carcinoma(Interim Follow-up Analysis)

BackgroundHepatocellular carcinoma(HCC)ranks 6th among the most common cancers and 3rd among the causes of death.China is a country with high incidence of HCC.According to latest data,there are 854,000 new cases of HCC in the world every year,and 466,000 cases in China,accounting for 55%of the world.This means that half of the new cases of HCC in the world are Chinese.In recent years,both surgical treatment and drug treatment have improved the quality of life of HCC patients.However,HCC is also a malignant tumor with a high tendency of recurrence,with a 5-year recurrence rate of over 70%after radical resection.Recurrent hepatocellular carcinoma(RHCC)treatment strategies including Transcatheter Arterial Chemoembolization(TACE),molecular targeted therapy,immune therapy,these are non-radical therapy and re-resection,radiofrequency ablation,liver transplantation,these are radical therapy.However,due to the shortage of donors and other reasons,only a small number of RHCC patients are expected to receive liver transplantation,and the majority of patients are still treated by surgical resection and radiofrequency ablation.As the main strategy for the treatment of HCC,traditional open hepatectomy has disadvantages such as large intraoperative blood loss,more perioperative complications,and longer hospital stay,etc.,while laparoscopic hepatectomy is superior to open surgery in these indicators,and the long-term results are comparable to that of open surgery.From the declaration of louisville in 2008 to the proposal of Morioka consensus in 2014,with the progress of laparoscopic hepatectomy technology in major hepatobiliary surgery centers around the world,the current laparoscopic hepatectomy has been achieved without surgical restrictions.Studies have shown that laparoscopic hepatectomy for RHCC is safe,feasible and effective.Radiofrequency ablation is another treatment method that can achieve radical therapy,especially in the patients with recurrent small HCC,compared with open surgery,which can achieve the same long-term efficacy of what open surgery can not be compared with the advantages of minimally invasive,short hospital stay,high patient satisfaction.Although laparoscopic liver resection and radiofrequency ablation for RHCC can achieve satisfactory effect,however,when compared with RFA,LH inevitably exist abdominal cavity adhesion due to the initial open surgery,which make the application of laparoscopic hepatectomy from RHCC treatment,also may increase the risk of intraoperative complications.Meanwhile,although radiofrequency ablation is as effective as surgical resection in the treatment of small hepatocellular carcinoma,incomplete lesion damage may occur in the treatment of large diameter recurrent tumors compared with laparoscopic hepatectomy.So the jury is still out on RHCC treatment options.Stuties on the curative effect of RHCC of laparoscopic hepatectomy and radiofrequency ablation across the world,mainly conductssmall sample size of retrospective study,or separately discusses the laparoscopic hepatectomy and radiofrequency ablation treatment for RHCC and the feasibility of the short-term curative effect of descriptive study.There are is still lack of prospective,randomized,controlled higher level of evidence-based medicine recommendation on the choices of RHCC radical treatment.ObjectiveThis study aims to conduct a comparison of LH and RFA in perioperative and long-term results of through prospective randomized controlled trial,and discuss preliminarily on overall survival and re-recurrence influenced by certain factors after treatment.Provide an option on higher level of evidence-based medical.Methods and ResultsFrom September 2016 to September 2017,RHCC patients eligible for enrollment were enrolled in the First Affiliated Hospital of Army Medical University.After the informed consent of the patients and the decision to be enrolled,the patients were randomly a ssigned to the laparoscopic hepatectomy group(LH)and radiofrequency ablation group(RFA).According to the online sample size statistical analysis system(www.ncss.com),the total sample size was calculated according to the difference test method.This study has been approved by the ethics committee of the First Affiliated Hospital of Army Medical University.The ethical approval number:2017KY(34),and it has been registered on ClinicalTrails.Gov,registration number:NCT03313648.This study was supported by the major technology innovation project(SWH2016ZDCX2015)of the First Affiliated Hospital of Army Medical University.The operative time of the patients was taken as the time point of 0.The patients were followed up once a month in the first three months after the surgery,and once every three months after the surgery,with a total of three years of follow-up.The mid-term follow-up analysis was conducted until the second year after the surgery.The patients were followed up by outpatient review and telephone,including blood test,liver function,alpha fetoprotein(AFP),HBV-DNA quantification,contrast-enhanced abdominal CT or tumor-specific magnetic resonance.When the patient is reviewed,if there is a new tumor diagnosed in the above imaging examination,it will be judged as recurrence.If the patient died during the two-year follow-up period,the survival period was from the first day after the operation to the date of death.The perioperative indicators and long-term results of the two groups were compared and analyzed using SPSS 22.0 statistical software.W test was used to test the normality.Measurement data were expressed as mean standard deviation,independent sample t test was used for comparison between groups,and X~2 test was used for classification variables.Kaplan-meier method was used to calculate the cumulative survival rate and Disease-free survival rate,and GraphPad PRISM 7.0a software was used to draw the survival curve.Univariate analysis was tested by log-rank method,and statistically significant clinical factors were screened to be included in COX risk regression model,and multivariate analysis was performed by stepwise forward method.Test levelα=0.05,P<0.05 was considered statistically significant.Preoperative indicators to be observed:gender,age,hepatitis B,cirrhosis,alpha fetoprotein(AFP),Child-Pugh grade,BCLC stage,liver function,platelet(PLT),size of recurrent tumor,number of recurrent tumor,number of primary tumor,size of primary tumor,etc.Intraoperative indicators to be observed:operation time,intraoperative blood loss,intraoperative blood transfusion rate,conversion to laparotomy rate.Postoperative and follow-up indicators to be observed:postoperative feeding time,postoperative time out of bed,length of hospitalization,perioperative complications(peritoneal hemorrhage,postoperative fever,intraoperative hydrops,ascites,pleural effusion),2-year overall survival,2-year disease-free survival,death,recurrence,loss of follow-up,etc.Perioperative period in the two groups had no incision infection,bile leakage,perioperative death and liver failure occurs,LH group 1 case of postoperative intraperitoneal bleeding,after laparotomy,the reason for liver section of small veins rupture hemorrhage,properly handle after the restore smoothly discharged,3 cases of postoperative fever,(2 cases attribute to liver section package effusion,1 cases of deep vein catheter related infections cause fever),8 cases of postoperative ascites,2 cases wi th pleural effusion.In RFA group,1 case presented pleural effusion,1 case presented postoperative fever,and 1 case presented ascites.There was no significant difference in perioperative complications between the two groups except ascites(P<0.05).The operative time of LH group was(187.822±75.179)min.RFA group(15.890±5.632)min,P<0.05.Intraoperative blood loss was(261.600±257.731)ml in LH group,(2.289±2.281)ml in RFA group(P<0.05),length of hospital stay was(15.067±4.180)d in LH group,and(6.200±2.904)d in RFA group.(P<0.05),LH group(2.822±0.936)d,RFA group(1.000±0)d,RFA group(2.978±1.994)d,RFA group(1.022±0.149)d,there were 3 cases of intraoperative blood transfusion in LH group(P<0.05),and no intraoperative blood transfusion in RFA group(P>0.05).Except that there was no statistical difference between the indexes of postoperative ascites and intraoperative bleeding in the RFA group and the LH group,other perioperative indexes were better than those in the LH group.Patients in both groups did not turn to laparotomy.We put gender,age,AFP,preoperative liver function,the Child–Pugh grading,hepatitis B infection,tumor size,number,liver cirrhosis,operation method and the degree of pathological differentiation respectively into univariate analysis,results show that the number of tumor recurrence,the number of primary tumor,the degree of pathological differentiation is the related factors that affect overall survival after surgery patients with recurrence;surgical method,alpha fetoprotein,number of recurrent tumors and number of primary tumors were the related factors that affected disease-free survival.The results of multivariate analysis showed that the primary and recurrent tumors were multi-occurred and the pathologic differentiation was low,which was an independent risk factor for the postoperative survival of patients with RHCC.The surgical method was radiofrequency ablation,and alpha fetoprotein>200 ug/L was independent risk factor for disease-free survival of patients with RHCC cancer after surgery.Follow-upAfter 1-24 months’follow-up,the median follow-up time was 22 months,and there were no lost cases in the two groups.So far,there were 23 cases of recurrence and metastasis in the LH group and 36 cases of recurrence and metastasis in the RFA group during the interim follow-up period.The 1-year and 2-year survival rates were 71.1%and48.9%in LH group.RFA group 26.7%,20.0%;The difference between the two groups was statistically significant(P<0.05).Extrahepatic metastasis occurred in 5 cases of LH group,including right adrenal gland,abdominal wall,lumbar vertebra,lung and rectum metastasis,among which 2 cases were combined with portal vein carcinoma thrombus.In the RFA group,there were 5 cases of extrahepatic metastasis,including 2 cases of lung metastasis,1case of diaphragmatic metastasis,1 case of upper diaphragmatic lymph node metastasis,and 1 case of peritoneal metastasis.The 1-year and 2-year overall survival rates were 93.3%and 91.1%,respectively,in the LH group.In RFA group,88.9%and 84.4%(P>0.05),the difference was not statistically significant.Conclusion1.The interim follow-up analysis showed that,for selected patients with RHCC,the disease-free survival rate of LH was better than that of RFA,while the overall survival rate of RHCC treated by the two surgical methods showed no significant difference.2.The number of primary and recurrent tumors and the degree of pathological differentiation were independent factors affecting the overall survival of patients with RHCC.Surgical approach and AFP were independent factors for disease-free survival.3.This study compared the perioperative indicators and long-term results of LH and RFA in the treatment of RHCC through RCT for the first time,providing a higher level of evidence-based medical evidence for the option of treatment for RHCC patients.4.This interim study showed the defection of insufficient cases,single center and short follow-up time,etc.,which needed to be supported by multi-center,large sample,RCT and long-term follow-up to provide evidences for the conclusion of this study.