| BackgroundPrimary liver Cancer is one of the common malignant tumors, it is the second cause of cancer-related mortality worldwide. Nearly 500,000 patients worldwide are diagnosed with hepatocellular carcinoma annually, and the incidence in the united states is increasing dramatically. Surgical treatment of hepatic cancer resection is the major method in the treatment of liver cancer. Nevertheless, the high recurrence is the main factor affecting the survival of patients after liver resection for hepatocellular carcinoma. The recurrence rate at 2 years after liver resection were 35-50%, five years were 61.8%, even if the small hepatocellular carcinoma recurrence rate is about 40% after the surgery. Therefor, how to delay the high recurrence rate is one of the focus in the study of the comprehensive treatment of liver cancer postoperative.Intraarterial therapy for a variety of hepatic malignancies represents an important therapeutic procedure in individuals with liver-dominant neoplasms. At present, the application of the interventional treatment acccounted for 61.9% of the total number of patients with liver cancer in our country. It is the main method in patients with advanced hepatocellular carcinoma. In 2011, the diagnosis and treatment of primary liver cancer standardization of Chinese Ministry of Health point out:postoperative interventional treatment decrease the recurrent rate of primary liver cancer after surgical resection obviously, and through the hepatic arteriography we could found some minimal residual disease that the CT or MRI could not found these. At domestic and foreign, there are many randomized controlled trial research that interventional treatment to prevent tumor recurrence and improve survival benefit, the conclusion indicated that the interventional therapy could reduce the recurrence rate and improve the total survival rate after curative resection. At present, the mostly common method were transhepatic arterial infusion (TAI) and transcatheter arterial chemoembolization (TACE). The purpose of this study are to evaluate postoperative transcatheter arterial chemoembolization (TACE) and transhepatic arterial infusion (TAI) for imporving the disese-free surivival of HCC patients after hepatectomy.PurposeThe purpose of this study are to evaluate postoperative transcatheter arterial chemoembolization (TACE) and transhepatic arterial infusion (TAI) for imporving the disese-free surivival of HCC patients after hepatectomy.Materials and Methods1. Retrospective analysis the efficacy of the transhepatic arterial interventional therapy after liver resection for hepatocellular carcinoma79 primary liver cancer patients were followed up after hepatectomy retrospectively from Jun 2011 to Jun 2012. All patients undergone interventional operation after hepatectomy 1-3 months. The followed-up endpoint is Jun.2013. They were divided into 2 group:41 had postoperative TACE,38 had postoperative TAI. Before interventional operation, two groups of patient’s age, gender, preoperative liver function Child-Pugh score, tumor size and AFP level had no difference. Using Chi-square test to compare two groups of 1 year recurrence rate, Kaplan-Meier estimation method compare disease-free survival rates, t test to compare the average difference of the averaged hospitalization stay. Software SPSS 13.0 package were used.2. Randomized study of transhepatic arterial interventional therapy as an adjuvant therapy for primary liver carcinoma after hepatectomyFrom October 1,2012 to June 30,2014, the patients for curative surgical resection and preventive interventional therapyof primary hepatocellular carcinoma in our hospital, it was prespectively randomized into two group:transcatheter arterial chemoembolization (TACE) or transhepatic arterial infusion (TAI).All patients follow-up end-point was December 31,2014. During the follow-up period the intrahepatic recurrence and metastasis as the end-point. At the same time, the liver function index that peroprative 3 days,3 days postoperative and 1 month were collection in patients.Software SPSS 17.0 package were used for date analysis. Measurement date with mean±standard deviation (χ±s),it was compare by t test.Paired t test was used to compare the Child-Pugh Class, AST, ALT, TB, ALB, PT before and after interventional treatment.Person x2 or Fishers Exact test was used to compare categorical varriables. Kaplan-Meier estimation method was used to compare the disease-free survival rates and median survival and to plot the survival curve. Log rank test was used to compare the recurrence-free survival curvers between TACE group and TAI group. The effects of covariates on survival time, group, age, gender, liver disease background, Child-Pugh Class, AFP, number of tumor, tumor size, tumor capsule, portal vein (or bile duct) tumor thrombosis, Tumor differentiation degree, number of interventional treatment were assessed used Cox proportional hazards model. A Log rank analysis was performed to identify which factors predict the recurrence-free survial time. P values less than 0.05 were considered statistically significant.Results1. The results of Retrospective analysis of the transhepatic arterial interventional therapy after liver resection for hepatocellular carcinomaIn 79 patients,11 were confirmed recurrence. The 1 year overall recurrence rate was 13.9%, TACE group 1 years recurrence rate was 12.20%, the TAI group is 15.79%, there were no difference of the 1 year recurrence rate between the TACE and TAI (χ2=0.213,P=0.645). Group with average disease-free survival rates was (21.60±21.60 months), (17.38±17.38 months) for TAI group, TAI group is obviously better than the TAI group (χ2=4.29, P= 0.038).The average hospitalization days and hospitalization expenses there was no significant difference (t=0.646, P=0.522)2. Efficacy of postoperative transhepatic arterial interventional therapy for patients with hepatocellular carcinoma(1) The choice of research objectAccording the inclusion criteria,23 cases of liver cancer patients were excluded, a total 124 patients were prespectively randomized into two group:transcatheter arterial chemoembolization (n=62) and transhepatic arterial infusion (n=62), after the research began 16 cases were excluded. Finally,108 patients (TACE group 52 cases, 56 cases of group TAI) entered this study. Of these,89 were male and 19 were female, with a mean age of 48.88±11.37 years (range,26-71 years).(2) Two groups of patients with baseline comparion before interventional therapyThere were no statistically significant differences in age, gender, liver disease background, Child-Pugh Class, AFP, number of tumor, tumor size, tumor capsule, portal vein (or bile duct) tumor thrombosis, Tumor differentiation degree, interventional therapy first time between the two groups.(3) The disease-free survival factors after resection of hepatocellular carcinomaThe clinical date of group, age, gender, liver disease background, Child-Pugh Class, AFP, number of tumor, tumor size, tumor capsule, portal vein (or bile duct) tumor thrombosis, Tumor differentiation degree, number of interventional treatment were used as covariates in survival time as the dependent variable, first for univariate Cox regression model analysis showed that three factors was statistically significant covariates factors, that group (P=0.008, RR=3.047), tumor capsule (P=0.001, RR=3.617), and portal vein (or bile duct) tumor thrombosis (P=0.000, RR=6.760).Then these three statistically significant factors as covariates in survival time as the dependent variable for multivariate Cox regression analysis, the results still prompted these factors were significantly different, group (P=0.001, RR=3.164) tumor capsule (P=0.000, RR=29.456), and portal vein (or bile duct) tumor thrombosis (P=0.000, RR=7.833). In summary,the methods of interventional treatment, tumor capsule, portal vein tumor thrombosis were the main factors influencing the disease-free survival for patients with primary liver carcinoma after hepatectomy.(4) The recurrence-free survival rate and overall survival comparedAt the end of the study,41 cases occurred in the end of the event, namely tumor recurrence or metastasis, the recurrence rate was 37.96%. The recurrence rate of TACE group was 34.62%(18/52), and the TAI was 41.07%(23/56). The total disease-free rate was 62.04%, the disease-free rate of TACE group was 65.38% (34/52) and TAI group was 58.93%(33/56), the Log-rank analysis showed that the disease-free survival rate had significant statistical significance in patients of two groups (χ2=4.021, P=0.045). The mean disease-free time of TACE was 21.78 months, the TAI group was 18.69 months. Using the Life Tables draw the disease-free survival rate during the follow-up, the cumulative recurrence-free rate were 100%, 96% and 74% at 6,12 and 18 months, respectively; the TAI group were 95%,91% and 58%.In TACE group, the follow-up time was 5-26 months, average follow-up time was 16.67 months of 52 patients. At the end of the study,18 cases occurred in the end of the event, namely tumor recurrence or metastasis. Of which recurrence occurred in 11 case and metastasis in 7 cases (including pulmonary metastasis(n=3), lymph node metastasis (n=2), lumbar metastasis (n=1), brain metastasis (n=1)).In TAI group, the follow-up time was 6-23 months, average follow-up time was 17.25 months of 56 patients. At the end of the study,23 cases occurred in the end of the event, namely tumor recurrence or metastasis. Of which recurrence occurred in 16 case and metastasis in 7 cases (including pulmonary metastasis(n=3), lymph node metastasis (n=3), lumbar metastasis (n=1)).(5) The risk factor of group, portal vein (or bile duct) tumor thrombus and tumor capsule impact to Disease-free survivalA total of 27 patients that the pathology show the portal vein (or bile duct) tumor thrombus and tumor with incomplete capsule (14 cases of TACE,13 cases of TAI). In the end of the research, there were 25 cases occurred hepatocellular carcinoma recurrence or metastasis, the recurrence rate was 92.59%, including TACE was 92.86%(13/14) and TAI 92.31%(12/13). The average recurrence-free survival time of TACE was 19.45 months, the TAI was 14.56 months. The Log-rank analysis showed that the disease-free survival rate had significant statistical difference in patients of two groups (x2=8.989, P=0.003). Therefor, the TACE is superior to TAI in improving the disease-free survival for patients that the portal vein (or bile duct) with tumor thrombosis and tumor with incomplete.In the study, the pathology of 26 patients after surgical resection show that the portal vein (or bile duct) tumor thrombus and tumor with complete capsule existed (including 12 cases of TACE group and 14 of TAI). There were 11 cases occurred in the end of the event, namely tumor recurrence, the recurrence rate was 42.31%. The recurrence rate of TACE group was 33.33%(4/12), and the TAI was 50.0%(7/14). The mean disease-free time of TACE was 21.23 months, the TAI group was 17.28 months. Although The Log-rank analysis showed the disease-free survival rate had not significant statistical difference (P> 0.05), but the Kaplan-Meier curve shows that with the increase of the research number, the preventive TACE will decrease the recurrent rate of Primary liver cancer after surgical resection.(6) The usage of micro catheter in interventional therapyIn this research, the 108 patients for hepatocellular carcinoma underwent 219 times of TACE or TAI treatment. The TACE were 122 times and TAI were 97 times. TACE group using micro catheter 32 times, the utilization rate was 26.23%, TAI group using micro catheter 11, utilization rate of 11.34%(χ2=7.592, P=0.006)(6) Effect of interventional therapy on liver functionIn the study,108 patients had received 219 times interventional therapy. The TACE were 122 times and TAI were 97 times. The Child-Pugh score, AST, ALT, TBIL, ALB and PT between two groups had no statistical differences. Child-Pugh score were finished before therapy. In Table 5, The laboratory examinations in three days after interventional therapy showed that Child-Pugh score, AST, ALT, TBIL and PT were on the rise while ALB showed a downward trend (p< 0.05). One month later, they all returned to pre-operation level. In group TAI, The level of Child-Pugh score, AST, ALT and TBIL were higher than those of pre-operation, ALB was still showed a downward trend (p< 0.05), but there were no differences in PT before and after therapy. In short, compare with TAI, the TACE bring more severe injury for patients liver function. The liver function injury has returned to the preoperative leverls after 1 months.(8) ComplicationsIn this research, the 108 patients for hepatocellular carcinoma underwent 219 times of TACE or TAI treatment. The main complications were fever nausea, vomiting, liver area pain and others mild complications.89 times experienced fever (40.64%). The fluctuations in body temperature 37.2℃～℃, average 38.5± 1.02℃.107 times of occurrence of nausea, vomiting and other gastrointestinal reactions (48.86%),63 times of liver pain (83%). In this study all therapy were preventive interventional therapy, so we used the minimal dosage of chemotherapy drug and iodized oil. The mild complications were alleviated after medication with 1 weeks.Conclusions1. Our retrospective study showed the preventive transcatheter hepatic artery interventional therapy could significantly improve the recurrence-free survival time of Primary hepatocellular cancer after surgical resection. And the TACE is superior to TAI in improving the disease-free survival.2. The interventional treatment, portal vein (or bile duct) tumor thrombus and tumor capsule were the independent risk factors that influence the disease-free survival time of patients with helatocellular carcinoma after curative surgical resection.3. In the randomized controlled study showed, the adjuvant TACE is superior to TAI in improving the disease-free survival for patients that the pathology show the portal vein (or bile duct) with tumor thrombosis and tumor with incomplete.4. Although preventive transhepatic arterial treatment in improve disease-free survival after surgical resection of primary liver cancer patients have certain advantages. But the TACE bring more severe injury for patients liver function than TAI, and the usage of micro catheter increased at the same time. |
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