Clinical Observation And Experimental Research On Hepatocellular Carcinoma Treated With Shen Tao Ruan Gan Recipe

Objective1)To make retrospective analysis about primary Hepatocellular Carcinoma(HCC) about disease,symptom and syndrome from literature sources;To summarize the theory of HCC about diease,symptom and syndrome;To explore the relationship between diease,symptom and syndrome.To identify the influence of some clinical factors on prognosis and to observe the therapeutic effect Shentao Ruangan Recipe(STR) in the treatment of stageâ…¢orâ…£of HCC.2)To investigate the regulatory effect of STR on the growth of H₂₂ tumor and the expression of vascular endothelial growth factor(VEGF) in transplanted H₂₂ tumor of mice.MethodsClinincal study1)154 cases of inpatients and outpatients of stageâ…¢orâ…£of HCC in the first affiliated hospital of Guangzhou University of TCM were enrolled between January 2007 and January 2009.Based on diagnostic criteria for HCC,clinical investigation cases were collected,clinical common symptoms and signs were analysed,occurrence of TCM types were summarized.2)154 cases of stageâ…¢orâ…£of HCC were analyzed about the relationship among diease,symptom and syndrome.3)154 cases of stageâ…¢orâ…£of HCC were followed up,prognosis influence of nine clinical prognostic factors such as gender,age,clinical stage, treatment methods,pre-treatment tumor size,Karnofsky score before treatment, TCM Syndrome,AFP level and Child-Pugh classification were analyzed using Kaplan-Meier's method and COX model.4)47 cases were divided into 15 cases of TCM group and 32 cases of combined group.TCM group was treated by oral taking of STR and Huaier-granula and it also was accomplished with diagnosis and treatment based on an overall analysis of the illness and the patients condition.While combined group was treated with TACE(chemoembolization) and ablation combined with TCM.21 cases of Western group were enrolled in the first affiliated hospital of Guangdong College of pharmacy which treated only interventional method.The clinical efficacy of treatment in the three groups was evaluated by the change of tumor size reducing rate and KPS scores and the liver function.Experimental studyThe transplant tumor model of H₂₂ hepatocarcinoma in mice was established.Forty mice were randomly divided into four groups,the CTX group,the STR low group, the STR high group and the control group,they were treated respectively with imtraperitoneal injection of CTX 20mg/kg/day,oral administration of STR in a dose of 0.86g/kg,1.34g/kg and equal volume of saline,the medication was given for 14 times totally.Twenty-four hours after the last administration, we calculated the tumor volume;The weight of the transplanted tumor mass were detected to work out the inhibitory rate;The histological and ultra structural changes in tumor tissue were observed by Hematoxylin-eosin(HE) staining; VEGF expression in tumor tissue was detected by S-P immunohistochemistry method.ResultsClinincal study1)Date analysis:Different treatment in terms of age with significant difference(P＜0.05);in terms of genger between TCM group and the other groups with no significant difference(P＞0.05);in terms of clinical stages with no significant difference(P＞0.05);in terms of liver function classification with significant difference(P＜0.05).the liver function class A and B with significant difference(P＜0.05).Different Child-Pugh class in terms of age with no significant difference(P＞0.05);in terms of genger with significant difference(P＜0.05);in terms of clinical stages with significant difference (P＜0.05),periodâ…¢andâ…£with significant difference(P＜0.05).The most common symptoms of stageâ…¢orâ…£of HCC were upper abdominal mass,liver pain, body weight loss,fatigue,pulse string.Common TCM syndrome type was weak spleen and strong liver functions type(71.43%).2)Correlation analysis:The correlation between syndrome type and symptom had no significant difference(P＞0.05).Upper abdominal mass had positively correlated with clinincal stage(P=0.008),The correlation between the other symptoms and clinical stage had no significant difference(P＞0.05).Upper abdominal mass had positively correlated with Child-Pugh classification(P =0.000),Body weight loss and fatigue had positively correlated with Child-Pugh classification(P=0.047,P=0.001).The correlation between syndrome type and clinical stage had no significant difference(P＞0.05). Dampness-heat of liver and gallbladder had positively correlated with Child-Pugh classification(P=0.041).The correlation between the other syndrome type and Child-Pugh classification had no significant difference.3)Prognosis analysis:The average survival time of 154 patients of HCC was 548 days,the overall median survival time(MST) of was 380 days,3 months, 6 months and one year survival rate was 73.4%,63.0%and 47.2%respectively.9 potential factors were analyzed:single-factor analysis showed that five factors such as clinical stage,treatment modalities,TCM syndrome type, AFP level before treatment,Child-Pugh classification were statistically significant.Multi-factor analysis showed that Child-Pugh grade of liver function was significant for survival.4)Tumor efficacy evaluation:The tumor size reducing rate was 0%and the tumor size stabilizing rate was 53.33%in TCM group,the tumor size stabilizing rate of theâ…¢period reaching 100%was the highest.While those in combined group was 15.63%,81.25%respectively,the tumor size stabilizing rate of theâ…¢period reaching 90%was the highest.While those in western group was 14.28%,80.95%respectively,the tumor size stabilizing rate of theâ…¢period reaching 85.71%was the highest.5)The quality of life score evaluation:The improve rate in TCM group was 60 %,compared with before treatment,the difference was no significant(P＞0.05).combined group was 59.38%,compared with before treatment,the difference was no significant(P＞0.05).Western group was 33.33%,compared with before treatment,the difference was no significant(P＞0.05).6)Liver function classification evaluation:After treated,TCM group and combined group,compared with before treatment,the difference was significant (P＜0.05).Western group,compared with before treatment,the difference was no significant(P＞0.05).7)Liver function evaluation:TCM group:in the middle of treatment and after treatment of ALT,AST,ALP,GGT,TB,IB,TBA,AFU,compared with before treatment, the difference was no significant(P＞0.05).ALB was decreased,the difference was significant(P＜0.05).After treated,DB increased,PA decreased,the difference was significant(P＜0.05).Combined group:After Intervention 1 week and 4 weeks of ALT,AST,ALP,GGT,TB,DB,IB,TBA,AFU,compared with those before treatment,the difference was no significant(P＞0.05).ALB was decreased,the difference was significant(P＜0.05).After Intervention 4 weeks of PA was decreased,the difference was significant(P＜0.05).Western group: After Intervention 1 week and 4 weeks of ALP,GGT,DB,IB,TBA,AFU,compared with those before treatment,the difference was no significant(P＞0.05).After intervention 1 week of ALT,AST,TB was increased,PA decreased,the difference was significant(P＜0.05).After Intervention 4 weeks of ALT,AST,TB,PA, compared with those before treatment,the difference was no significant (P＞0.05).Experimental study1)All mice model were inoculated successful,the tumors success rate was 100 %.liver transplantation subcutaneous model was successfully completed.2)STR groups and the model group had significant effect on inhibiting the tumor weight(P＜0.05),when compared with the model group.The tumor inhibition rate was 32.9%in the low STR group;the tumor inhibition rate was 38.9%in the high STR group.3)HE staining results showed that there were different degree of cell necrosis zones,split-phase reduction of tumor cell in tumor tissues of high-dose group and low-dose group.4)The expression of VEGF:The results showed that the positive rate of VEGF of high-dose group and low dose group and CTX group were significantly lower than model group(P＜0.05).High-dose group and low dose group,compared with CTX group were no significant difference(P＞0.05).High-dose group and low-dose group also were no significant difference(P＞0.05).Conclusion1)Shentao Ruangan Recipe can stable tumor,improve KPS score and prolong the survival time of stageâ…¢orâ…£of HCC.It can also reduce the damage to liver function caused by invasive treatment such as interventional and ablation.2)STR could obviously inhibit the growth of H₂₂ hepatocarcinoma and its mechanism may be related to the down-regulation of the protein expression of VEGF in tumor tissue.