Regional intra-arterial infusion chemotherapy for pancreatic cancer of dogs with the mixture of lipid emulsion-cisplatin: an experimental study

Objective To approach the mechanism and efficacy of regional intra-arterial infusion chemotherapy with the mixture of lipid emulsion-CDDP (LE-CDDP) for treatment of locally advanced pancreatic cancer. Methods 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 2 ml/kg/ body weight (group A) and 1 ml/kg/bedy weight (group B), respectively. Normal sodium (NS) as a solvent was used as control with 2 ml/kg/bedy weight (group C) and 1 ml/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. Blood samples were collected after infusion at 0,3,5,10,20,30,40,50,60 min and the tissues were obtained after the 60 min's blood sample was collected. Blood samples, absorbent gland in peripancreas, liver, spleen, kidney, heart, portal vein, the superior segment of jejunal and pancreas and parapancreatic tissues were obtained for CDDP concentration analysis and histopatholngic examination. Results The values of the area under curve (AUC), the incipient serum concentration ( C0 ) and the elimination half-life (t1/2 ) of the serum CDDP concentration-time curve in four groups were A (54. 5 ± 10.1)%,(2.6±0.5) mg/L, (16.7±3.6) min;B (18.3±6.0)%,(1.5±0.2) mg/L, (47.9 ± 11.1) min; C (116.7±20.6)%, (6.5±0.4) mg/L, (10.5±2.8) min and D (126.6±30.7)%, (5.5±0.4) mg/L, ( 10. 1±3. 1 ) min, respectively. There were significant difference among these four groups ( F(AUC) = 42. 42, F(C0) = 249. 61, F( t1/2 ) = 12. 48, P 0. 05 ). Perivascular lymphocytic and neutrophilic infiltration, congestion and hemorrhage were found in the pancreas, parapancreatic absorbent gland, liver and spleen in the group A and group B. The micro-particles of intralipid were present in the capillary vessel of these tissues. No specific pathological changes were found in other groups and organs. Conclusions 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. Key words: Pancreatic neoplasms;  Fat emulsions, intravenous;  Cisplatin;  Radiography, interventional;  Animal experimentation