Catheter Placement Method And Pharmacokinetic Study Of Internal Bedside Hyperthermic Intrathoracic/Intraperitoneal Chemotherapy

【Background】Hyperthermic intrathoracic chemotherapy（HITHOC）and hyperthermic intraperitoneal chemotherapy（HIPEC）is a new treatment modality in which chemotherapeutic drugs were formulated into an infusion solution and then circulated at a constant temperature（43°C）through a thermal perfusion therapy machine.According to the different ways of catheter placement,it can be divided into surgical and internal medical types.In recent years,HITHOC and HIPEC have been increasingly used,but there is still a lack of standardized practice.【Objective】1.To compare the difference of flow velocity and temperature between surgical catheterization and abdominal puncture catheterization in HIPEC by animal experiments.2.Establish a method for the determination of cisplatin concentration in artificial hydrothorax and ascites and plasma by high performance liquid chromatography（HPLC）.3.To compare the differences in perfusate and blood concentrations of cisplatin and adverse effects of intravenous chemotherapy（IVC）,HITHOC and HIPEC.【Methods】1.Ten pigs were randomly divided into groups A,B and C.Group A was treated with four-point surgical HIPEC（pipe diameter 7.3mm）.Group B was treated with two-point internal medicine HIPEC（pipe diameter 4mm）.Group C was treated with two-point internal medicine HIPEC in the front 30 minutes,and four-point internal medicine HIPEC in the post 30 minutes（pipe diameter 2.7mm）.In all animals,intracavitary thermometers were placed in the left lower abdomen,left upper abdomen,right lower abdomen and right upper abdomen,and the initial temperature of each point was recorded.The flow velocity of perfusion fluid and the temperature of each point were recorded at 15,30,45 and 60 minutes of HIPEC,and the vital signs of the experimental animals were monitored during and after operation.2.Based on the existing methods,an HPLC method was developed for the determination of cisplatin concentration in artificial hydrothorax and ascites and plasma.3.The concentrations of cisplatin in perfusate and plasma were determined by HPLC in 60 patients who received cisplatin-based IVC,HITHOC or HIPEC in our department.The area under curve（AUC）and adverse reactions of the three groups were compared.【Results】1.The flow velocity and temperature of the three groups were compared by repeated measurement analysis of variance,and there was no significant difference among the three groups（P=0.214,0.305）.There was significant difference in flow velocity between group A and group C at 15 and 60 minutes（P<0.05）,but there was no significant difference among the three groups at other time points（P>0.05）.There was significant difference in temperature between group A and group B at 45 and 60 minutes,and between group B and C at 30 minutes（P<0.05）.There was no significant difference in temperature among the three groups at other time points（P>0.05）.The vital signs of all animals were stable during the operation and recovered well after operation.2.A HPLC method for the determination of cisplatin in artificial hydrothorax and ascites and plasma was established.The samples were treated with methanol as precipitant,complexed with sodium diethyldithiocarbamate（DDTC）,extracted with trichloromethane,dried with N₂ and re-dissolved with acetonitrile,and the mobile phase was set to 77%methanol-23%water.The results show that this method is suitable for the determination of cisplatin in artificial hydrothorax and ascites and plasma.3.The mean value of AUC_{0-24 h} of cisplatin in perfusate of HITHOC group（72.36μg/m L·h）was significantly higher than that of HIPEC group（36.03μg/m L·h）.The mean values of AUC_{0-24 h} in plasma of the three groups were 3.15μg/m L·h,2.57μg/m L·h,3.02μg/m L·h,respectively.There was significant difference between IVC group and HITHOC group（p<0.01）,but there was no significant difference between IVC group and HIPEC group（p=0.47）,and there was significant difference between HITHOC group and HIPEC group（p=0.01）.There was no significant difference in the incidence of common adverse events among the three groups.【Conclusions】1.Although the drainage tube of internal medical HIPEC is thinner,it can reach the level of surgical HIPEC in terms of velocity and temperature.2.HPLC method can effectively measure the content of cisplatin in artificial hydrothorax and ascites and plasma,which is simple and accurate.3.Internal medical HITHOC cannot achieve the systemic therapeutic effect of the same dose of cisplatin IVC,while internal medical HIPEC can achieve the systemic therapeutic effect of the same dose of cisplatin IVC.