Regional Intra-arterial Infusion Chemotherapy For Pancreatic Cancer With Solvent Of Lipid Emulsion: An Experimental Study

OBJECTIVE To determine the feasibility and efficacy of regional intra-arterial infusion chemotherapy with solvent of lipid emulsion(LE)for treatment of locally advanced pancreatic cancer.MATERIALS AND METHODSPartâ… .Twenty-four health dogs were divided into four groups(group A,B,C,and D).The dosage of CDDP was used in 4 mg/kg/body weight for each animal.The 20%LE,as a solvent,was used in the experimental animals with 2ml/kg/body weight(group A)and lml/kg/body weight(group B),respectively.Normal sodium(NS)as a solvent was used as control with 2ml/kg/body weight(group C)and 1ml/kg/body weight(group D), respectively.The LE-CDDP mixture and the NS-CDDP mixture were infused into the proximal segment of splenic artery under the DSA,with transfemoral arterial approach. The blood was sampled from the portal vein and femoral vein at immediately after,3 minutes,5 minutes,10 minutes,20 minutes,30 minutes,40 minutes,50 minutes,and 60 minutes,after the infusion.Blood samples,absorbent gland in peripancreas,liver, spleen,kidney,heart,portal vein,the superior segment of jejunal and the head,body and tail of pancreas were obtained for CDDP concentration analysis and histopathologic examination.Partâ…¡.To observe the effects of intra-arterial infusion on the pancreas with different concentration of LE.The dosage of the LE used were 2ml and 20ml,respectively.The experimental animals were divided into four groups,according to the concentration and the dosage of the LE infusion.The 20%LE was used in the groupâ… (2ml)and groupâ…¡(20ml).The 30%LE was used in the groupâ…¢(2ml)and groupâ…£(20ml).The infusion catheter was placed in the splenic artery and hepatic artery,respectively.The imaging frames of DSA were recorded for measurement of the contrast medium flowed from the catheter end to the selected branch of the arteries.RESULTS:Partâ… .The dynamic change of the serum CDDP concentration-time curve.The dynamic change of the serum CDDP concentration-time curve of all groups were similar. The mean CDDP concentration of the serum in the NS-mixture groups were higher than that of in the LE-mixture groups.The area under curve(AUC)and the maximum serum concentration(Cmax)of the curve in LE-mixture groups were lower than that of in the NS-mixture groups statistically.The elimination half-life(t_1/2)of the curve in LE-mixture groups was longer than that of in NS-mixture groups.Among LE-mixture groups,the CDDP concentration of the mixture in subgroup B was higher than that of in subgroup A.The AUC and Cmax of the curve in subgroup B were lower than in subgroup A significantly.The t_1/2of the curve in subgroup B was longer than that of in subgroup A significantly.The comparsion of the tissue CDDP concentration.The CDDP concentration of the tissues were too low to be measured in the NS-mixture groups.The tissue CDDP concentration of pancreas and spleen could be measured in LE-mixture groups. However,the other organs(liver,kidney,heart,the superior segment of jejunal)CDDP concentration in LE-mixture groups were too low to be measured.The concentrations of the body and tail of pancreas were higher in subgroup B than that of in subgroup A signficantly(t=2.523,p=0.03;t=2.727,p=0.02).The tissue CDDP concentration of the head of pancreas and spleen were no difference signficantly between the subgroup B and subgroup A.The pathologic findings.Perivascular lymphocytic and neutrophilic infiltration, congestion and hemorrahge were found in the pancreas,parapancreatic absorbent gland, liver and spleen in the LE-mixture groups.The micro-particles of intralipid were present in the capillary vessel of these tissues.No specific pathological changes were found in other organs.Partâ…¡.The organ blood flow velocity could be decreased by the LE intra-arterial infusion.The differences of the dosage and concentration of LE produced the different reduction of the blood velocity.The persistence time and the peak value were used as the measured index of the reduction.The persistence time was five minutes in groupâ… , five to ten minutes in groupâ…¡,twenty minutes in groupâ…¢,and twenty tothirty minutes in groupâ…£.The peak value of the reduced rate was 18 frames(1.44s)in groupâ… ,30 frames(2.4s)in groupâ…¡,9 frames(0.72s)in groupâ…¢,14 frames(1.12s)in groupâ…£. Compared to the 20%LE intra-arterial infusion,30%LE intra-arterial infusion could have longer persistence time but less decreased the blood flow velocity.CONCLUSIONS:The blood flow velocity could be slowed by the LE intraarterial infusion.The regional intra-arterial infusion with LE-CDDP mixture could increase the pancreatic CDDP concentration,meanwhile,it also could decrease the serum CDDP concentration.The more of the CDDP concentration in the LE-CDDP mixture,the more CDDP concentration at the pancreatic tissue accordingly.Regional intra-arterial infusion chemotherapy with solvent of 20%LE could be safe in the treatment of the advanced pancreatic cancer...