| Bacbound;With the deve1opment of surgica1 techniQues and perfection of perioprativeprocedures, 1iver cancer is now active1y resected. The rate of radica1 resectionhas been increased markedly. However, the prognosi s is sti 11 unsatisfactory becauseof the high rate of postoperative tumor recurrence due to residua1 micro--metastases,such hepatic micro--metastases may be attributed to the seeding of tumor ce1ls intoporta1 venous blood. 'In order to improve the surgica1 therapeutic outcome,postoperative chemotherapy is carried out in many institutions. With systemicchemotherapy the tumor response is often poor and systemic toxicity severe. Thus,.. -various reg1ona1 approaches (such as hepatic artery infusion, HAI) have beendeve1oped. Their aim is to restrict drugs to the tumor--bearing organ. Suchrestricted app1ications allow dosages higher than those achieved by systemicapp1 ication. Response rate after regiona1 chemotherapy for 1 iver tumor is increasedcompared with that after systemic administration. But the effect on surviva1 is1imited. As a regiona1 therapy for hepatic ma1ignancy, isolated 1iver perfusion(ILP) can a11ow the de1ivery of cytotoxic agents in high concentration to the 1iverwhile avoiding genera1 drug toxicity by preventing the general distribution of thecytoxic agents through the systemic circu1ation, resu1ting in maximum effects ofdrug upon tumor. Since ILP is more complex than other forms of drug de1ivery, itis care fu1ly used mainly in some un-resectab1 metastatic 1iver timors today. If itcan be used in resectab1e 1iver tumor, it may be maximize the drug effect toel iminate residua1 tumor ce11s, reduce high rate of postoperative tumor recurrence,and improve prognosis. However, Whether the body can to1erate ILP after 1argehepatectomy, is sti1l unknown. There is no report about the influence of ILP afterhepatectomy in 1iver and other organs. The present paper describes experiencedesigned to determine in the pig the to1erance of normal hepatic tissue tonormothermic hypoxic iso1ated 1iver perfusion (NHILP) with high dose of 5-f1uorouraci1 (200mg/kg body weight) after 1eft hepatectomy. The hepatic anatomyand physio1ogy of the pig are similar to these of the human, so know1edges andexperience taken from study in pig mode cou1d have direct app1icability to humanc1inica1 use.Materials and methods:Landrace breed male and female pigs ranging 2 to 3 months in age and 25 to 32 kg inweight were utilized for all exPeriments. An Y-shunt was inserted into the vena cava througha longitLIdinaI venotomy in the infrahepatc vena cava to shunt the spIanchnic and lowersystemic venous blood illto the suPrahepatic vena cava. l000ml Lactate Ringer's solutionwithout oxygenation wanned to 38 'C was used as the perfusate. The isolated liver perfusionwas performed in vivo for 20 minutes through the porta1 vein by gravity (70cm H2O) using avenovenous bypass. Following perfusion, washout of the liver was accomplished with at 1east1000ml Ringer's Lactate about l0 minates. The pigs were divided into 3 grouPs at random, with4 pigs in each grouP. GrouP Af peffosion with Ringer's Lactate only. GrouP Bf 5-Fu was addedto the perfusate at dose of 200mg/kg body weight. Group C(200mg/kg 5-Fu was added to theperfusate for NHILP after left hepatectomy. Drug leve1s both in the syStemic venous circulationand in the hepatic venous oLltflow were measured with high performance liquidchromatograPhic (HPLC) system, energy charge(EC) of hepatic tissue was checked also withHPLC system, Complete blood counts and serum levels of bilirubin, hepatic enZymes, bloodurea nitrogen(BU'N), and creatinine were measured prior to and following ILP. Wedge liverbiopsies were obtained prior to and immediately following ILP, as well as 4 weeks afteroperation. Tissues were fixed in neutral formalin, embedded in paraffin, and stained routinelywith hematoXylin-eosin. 4 weeks after hepatectOmy, the animal were killed, and t...
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