Intervention Improvement, Drugs Application And Evaluation Of Transarterial Chemoembolization For Rabbits With VX₂ Hepatoma

PartⅠImprovement of Transarterial Embolization of RabbitModels with VX2 Hepatoma and Imaging EvaluationObjective:To improve intra-arterial adminstration of rabbit models with VX2hepatoma and evaluate the manifestations of the VX2 hepatomas on mutislice spiralcomputed tomography (MSCT),colorful ultrasonography and digital subtractionangiography (DSA).Methods:Fifteen New Zealand white rabbits were inoculated with fragment of VX2hepatomas into the left lobe of liver.After 2 weeks,all the rabbits were proved withliver neoplasms by MSCT scanning and colorful ultrasonography.During the openlaparotomy,common hepatic artery was ligated temporarily before transarterialembolization (TAE),and a catheter was inserted via gastroduodenal artery monitoredunder a microscope and detained in rabbit's abdomen.TAE was performed on therabbits.And then let common hepatic artery reperfuse.MSCT scanning,colorfulultrasonography and DSA were performed to describe the features of rabbit hepaticneoplasmas.Results:TAE was successfully performed in 11 rabbits.One rabbit died foroverdosage of anesthesia.Another rabbit died for massive bleeding during thesurgeon.Artery anatomy mutations existed in two rabbits,so catheterization wasquitted.VX2 hepatomas appeared as low density nodule-like shadow on MSCTimagings,and showed low echoes,higher blood flow signals on colorfulultrasonography.Trans-gastroduodenal artery angiography showed that VX2hepatomas had nodule-like tumor stain mainly around the tumor in arterial phase.Conclusion:Superselective embolization can be performed by detained catheter viagastroduodenal artery during the open laparotomy and has little impact on hepatichemodynamics.DSA can be easily used to follow up by the detained catheter.Furthermore,operators can completely avoid radiation,but the requirements of condition and technology are higher than usual. PartⅡMSCT Effect study and Safety evaluation of TransarterialEmbolization Therapy with Nan Hydroxyapatite Particle on Rabbitswith VX2 HepatomaObjective:To study the effects of nan hydroxyapatite particle (nHAP) on rabbits withVX2 hepatoma,and analyze distribution and impact of nHAP and lipidol mixture inmain organs.Methods:45 rabbits implanted liver VX2 tumors were randomly divided into 3groups.Each group had 15 rabbits.All the rabbits were proved with liver neoplasmasby mutislice spiral computed tomography (MSCT).During the open laparotomy,common hepatic artery was ligated temporarily,and then a catheter was inserted viagastroduodenal artery under a microscope.Administration was performed by thecatheter on the rabbits.Group A (control group) was administrated with 0.5 to 1.0 mlsaline;Group B (lipiodol group) was administrated with 0.5 to 1.0ml lipiodol;GroupC (nHAP group) was administrated with 0.5 to 1.0ml 0.5% nHAP.MSCT scan wasperformed to measure tumor volume on the 7th day and 14th day after theintervention.Serum levels of AST and ALT were measured on the 1st day and 7th dayafter the intervention thrapy.The survivals of VX2 rabbits were also descriped.Another 6 rabbits with VX2 hepatomas were administrated with 0.5 to 1.0ml mixtureof nHAP and lipidol,and put them to death at regular intervals (1 hour and 24 hoursafter intervention).Distribution and impact of lipidol and nHAP mixture in vitalorgans were analyzed by pathological section and transmission electron microscope.Results:The tumor growth rates of group B and C on the 7th day and 14th day aftertreatment were lower than those of control group (P＜0.05).The tumor growth ratesbetween group B and C on the 7th day and 14th day after treatment were similar(P＞0.05).The life span of both group B and group C were longer than that of thecontrol group (P＜0.05).The serum levels of AST and ALT in all three groups werelittle higher than that of before the intervention (P＞0.05).The serum levels of AST or ALT in all groups became normal level on the 7th day after the intervention thrapy.Pathological sections showed cancer nesst and necrosis structures in VX2 hepatoma,and no abnormal structures in other organs.Under transmission electron microscope,distribution of nHAP and lipidol was found only in tumor tissues at both 1 hour and24 hours after intervention,but could't found in other organs.Conclusion:The interventional therapy with nHAP has signifigant inhibitory effecton rabbits with VX2 hepatoma,and can prolong the rabbits life span.There are noobvious liver toxicity by using the interventional therapy.Lipidol and nHAP mixturealways distribute in tumor tissues after transarterial intervention,and no nHAP can befound in other vital organs.There are no relative complications after nHAPintervention thrapy. PartⅢExperimental Study and Effect Evaluation ofTransarterial Chemoebolizasion with 5-FU Sustained-ReleaseMicrosphere on Rabbits with VX2 HepatomaObjective:To study the therapeutic efficacy of 5-FU sustained-release microspherechemoembolization through gastroduodenal artery on rabbits with VX2 hepatoma byradiology and pathology methods.Methods:40 rabbits implanted liver VX2 tumors were randomly divided into 4groups.Each group had 10 rabbits.All the rabbits were proved with liver neoplasmasby multislice spiral computed tomograpy (MSCT).During the open laparotomy,common hepatic artery was ligated temporarily,then a catheter was inserted viagastroduodenal artery under a microscope and administration was performed throughthe catheter.We ligated gastroduodenal artery and let common hepatic artery repefuseafter administration.Group A (blank control group) was administrated with 0.5 to1.0 ml saline;Group B (contrast agent group) was administrated with 0.5 to 1.0mlioversol injection;Group C (lipiodol group) was administrated with 0.5 to 1.0mllipiodol;Group D (5-FU sustained-release microsphere group) was administratedwith mixture of 10mg 5-FU sustained- release microsphere and lml ioversol.MSCTscan was performed to measure tumor volume on the 7th day after treatment.Thetumor growth rates,necrosis rates and the tumor apoptotic index (AI) were examinedand compared.Results:One week after treatment,in the 5-FU sustained-release microsphere group(group D) the tumor was significantly inhibited,tumor growth rate was lower than thegroup A and group B (P＜0.05),and was similar to group C (P＞0.05).The tumornecrosis rates of group D was singnificantly higher than those of group A and B(P＜0.05).The tumor AIs were 1.69±0.18 (group A),1.75+0.27 (group B),8.03+0.63 (group D),respectively (P＜0.05).AI of group D was singnificantly higher than thatof group A and B.Conclusion:5-FU sustained-release microsphere infusion through artery to liver caninhibit tumor growth,induce the apoptosis and aggravate the tumor necrosis.It is aneffective chemoembolization agent. PartⅣExperimental Study and Effect Analysis of TransarterialChemotherapy with Recombinant mutant TNF on Rabbits with VX2HepatomaObjective:To study the therapeutic efficacy of recombinant mutant human tumornecrosis factor (TNF) chemotherapy through gastroduodenal artery on rabbits withVX2 hepatoma.Methods:30 rabbits implanted liver VX2 hepatoma were randomly divided into 3groups.Each group had 10 rabbits.All the rabbits were proved with liver neoplasmasby multislice spiral computed tomograpy (MSCT).During the open laparotomy,commonhepatic artery was temporarily ligated,and then a catheter was inserted viagastroduodenal artery under a microscope and administration was performed throughthe catheter.We ligated gastroduodenal artery and let common hepatic artery repefuseafter administration.Group A (blank control group) was administrated with 0.5 to 1.0ml saline;Group B (lipiodol group) was administrated with 0.5 to 1.0ml lipiodol;Group C (recombined TNF group) was administrated with mixture of 2.5×10~4 IUrecombinant mutant TNF and 1ml saline.MSCT scan was performed to measuretumor volume on the 7th day after intervention.The tumor growth rates and necrosisrates were measured.Tumor apoptotic indexs examined by TUNEL were comparedbetween group A and C.VEGF expression and MVD of all groups were detected byimmunohistochemistry.Results:One week after treatment,in the recombinant mutant TNF group (group C)the tumor was significantly inhibited,tumor growth rate was lower than the group A(P＜0.05),and was similar to group B (P＞0.05).Tumor necrosis of group A wassignificantly different from group B and C,and the necrosis rate of group B and Cwas higher than group A (P＜0.05).Tumor apoptotic indexs (AI) were 1.69±0.18 ingroup A and 7.26±0.45 in group C,and there was singnificant difference betweengroup A and group C (P＜0.05).Vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) of group C were singnificantly decreased(P＜0.05).Conclusion:Recombinant mutant human TNF chemotherapy through artery to livercan inhibit tumor growth,reduce vescular growth and induce apoptosis and/or tumornecrosis.Recombinant mutant human TNF is an effective chemotherapy agent forrabbits with VX2 hepatoma.