Clinical Research On The Efficacy And Safety Of TACE With Interruption And Pressurization For Hypovascular Liver Cancer

Purpsose Hypovasculer liver cancer with thin feeding arteries and low neovesselsdensity is not uncommon clinically. However, when they were treated with theconventional TACE, chemotherapeutic and embolic agents were difficult to gain full accessinto the lesions, and very easy to reflux, which could aggravate the liver function and thegastrointestinal reaction. Thus it was a clinical difficulty for its poor lipiodol filling andtreatment response. The improvement of the efficacy of the hypovascular liver cancermight raise the overall survival and expand the application of TACE. This thesis is toinvestigate the efficacy and safety of TACE with interruption and pressurization, and toprovide a reference for the treatment strategy of the hypovasculer liver cancer.Material and Methods This is a randomized, single-blind and control trial. Patientsthat were diagnosed as hypovascular liver cancer by the imaging and required TACE wererandomly divided into the experimental and control group with a random number table.The experimental group was treated with TACE with interruption and pressurization(conventional catheter+balloon catheter+pressure pump), while the control group withthe traditional methods (conventional catheter). Each patient received at least2times ofTACE treatment, and then additional TACE was introduced every2to3months in case ofpermissive liver function if there was abnormal enhancement area in the postoperativeimaging, or keep on the follow-up every2to3months if there was no abnormalenhancement. The enhanced CT or MRI examination and the laboratory tests were adoptedto evaluate its efficacy and safety by the treatment response and the occurrence of adversereactions before and during the treatment afterwards and the follow-up. The efficacyindicators included the volume and grade of the intrahepatic lipiodol deposition, and thechange of the maximum diameter of the lesions (RECIST and mRECIST) and the tumormarker. The safety indicators included the adverse reactions after TACE (includingfever/chill, nausea/vomiting and abdominal pain), and the change of the laboratoryparameters (including TBil, ALT, GGT, PA and ALB) and the Child-Pugh grade for theliver function. The endpoint of the follow-up was the disappearance of the observablelesions (including death and secondary surgical excision). The t test was performed for thecontinuous data with or without (logarithmical transformation) normal distribution andhomogeneity of variance. The chi-square test was performed for the ranked data and the comparison of the constituent ratio between the two groups. The median time to the targetevent was calculated by the Kaplan-Meire method and compared by the Log-rank test. Theprognostic risk factors were filtered by the COX univariate and multivariate analysis. Itwas considered statistically significant for all statistical tests when p-value was less than0.05.Results A total of178patients were entered into the study cohort,89cases in eitherof the two group, and were proved to be with balanced baseline. The dose of the lipiodolused in the TACE, the volume of the intrapatic lipidol and the ratio of the volume of thelipiodol and the lesions in the experimental group were significantly higher than those inthe control group. The time to partial remission (TTPR) in the experimental group wassignificantly earlier than that in the control group by the RECIST (p=0.029), while therewas no significant difference in the time to progressive disease (TTPD). The incidence ofthe gastrointestinal adverse reactions in the control group was significantly higher than thatin the experimental group (p=0.011), which showed close relation to the bilateralembolization and drug reflux, but had nothing to do with the dose of lipiodol used in theTACE. There was no significant difference in the laboratory parameters and the liverfunction between the two groups in1.5months after the TACE. The occurrence of theextrahepatic metastasis in patients with tumor thrombus was significantly earlier than thatin patients without it (p=0.015, HR=2.535), though there was no significant differencebetween the two groups. The PA, BCLC stage, grouping by TACE and combining othertreatment were four independent prognostic factors during the univariate and multivariateanalysis. The patients with PA less than170mg/L (p=0.014) and in BCLC stage C(p<0.001) were seen to be associated with significantly worse survival. TACE in theexperimental group (p=0.042) and combined with other treatments (p=0.001) wereassociated with improved survival.Conclusion It was preliminarily proved that TACE with interruption andpressurization could result in significantly more lipiodol deposition in the hypovascularlesions, earlier partial remission and longer survival time. The applications of the ballooncatheter could reduce the regurgitation of chemotherapeutic agents and lipiodol,gastrointestinal adverse reactions and the damage to the normal liver parenchyma, and didnot show adverse effect to patients’ liver function and extrahepatic metastasis. Therefore,TACE with interruption and pressurization might be available and safe treatment for hypocascular liver cancer and have the value for further promotion.