Implantation Of Linear Iodine-125 Seeds Strand Attached To IVC-stent Combined With TACE For The Treatment Of HCC With IVC Malignant Obstruction: Experimental And Clinical Study

Part One:Animal ExperimentAnimal Experiment One:Experimental study on the implantation of iodine-125 seeds strand with two different doses into inferior vena cava in rabbitObjective:To evaluate the safty and feasibility of the treatment that the iodine-125 seeds strand implantation into inferior vena cava(IVC) in rabbit.Materials and Methods:Fourteen New Zealand white rabbits were randomly divided into two groups, including two seeds group (GroupA) and four seeds group(Group B) 7 rabbits respectively. Two or four 125I seeds(model 6711, Ao=0.7mCi) were sealed into a transparent catheter as a seed strand, Purse-string suture was done on the anterior wall of IVC after the laparotomy, and the iodine-125 seeds strand was inserted into IVC through the purse and suspensory fixed on the inner wall of IVC. The general conditions were monitored after operation. The post-operation body weight, routine blood and liver function were compared with those of pre-operation respectively. DS A or MDCT examinations of IVC were performed at 1st,2nd,4th,8th and 16th week after operation, respectively. MDCT examinations were performed with plain scan, arterial phase, portal phase and venous phase enhancement for all animals and 3D MPR were acquired. Rabbits were killed at 1st,2nd,4th,8th and 16th week post-operation respectively. IVC, the liver tissue less and more than 10mm away from the seeds strand and the intestine were examined with the gross and histological pathology.Results:The success rate of operations was 100%. No vomiting, diarrhea and death related to irradiation were observed in both groups. No significant changes was observed in the body weight, routine blood and liver function between two groups (P>0.05). IVC was patent in DSA, MDCT and 3D-MPR images. In gross examination, the target IVC is smooth, there are no perforation or mural thrombosis. No adherence was observed between the seeds strand and blood vessel. The histological examination showed necrosis and exfoliation of endothelial cells in IVC in both groups, but no obvious pathological changes in media and adventitia tunicae. Swelling and distension, cytolysis and necrosis of liver cells were seen near the seeds strand in both groups, and is more severe in Group B.Conclusion:Linear iodine-125 seeds strand intraluminal implantation into the inferior vena cava is safe and feasible. There are no significant different about radiation injuries in different dose.Animal Experiment Two:Establishment and evaluation study of implanted inferior vena cava tumor thrombus in rabbit modelsObjective:To establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT) and to evaluate its growth with MDCT and 3D-MPR.Materials and Methods:Tumor cell line VX2 was inoculated subcutaneously into rabbit to develop parent tumor, which was cut into small strip. Purse-string suture was done on the anterior wall of IVC after the laparotomy in twelve New Zealand white rabbits, the tumor strip was injected into IVC through the purse and suspensory fixed on the inner wall of IVC. The general conditions, body weight and the survival time were monitored after operations. MDCT examinations were performed with plain scan, arterial phase, portal phase and venous phase enhancement every week for all animals and 3D MPR were acquired. The volumes of IVCTT were calculated. IVC, IVCTT and metastasis were examined with gross and histological pathology.Results:The mean body weight of rabbits at the 6th week was 2.02±0.20kg. The mean survival time was 49.50±4.40 days. The IVCTT was confirmed by MDCT and 3D-MPR images. Collateral varicose veins caused by IVC obstruction and metastasis were also showed in images. IVCTT and metastasis were confirmed by pathology. The success rate of IVCTT was 100%.Conclusions:Injecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish IVCTT animal model. MDCT and 3D MPR are valuable method for monitoring the growth and metastasis of IVCTT in animal models. The model of implanted IVCTT of rabbit provides useful tool for the research of treatment of IVCTT.Animal Experiment Three:Experimental study on the treatment of the implanted inferior vena cava tumor thrombus in rabbit models with linear iodine-125 seeds strandObjective:To evaluate the effect of linear iodine-125 seeds strand on the implanted inferior vena cava tumor thrombus in rabbit model.Materials and Methods:Twelve New Zealand white rabbits with IVCTT were randomly divided into two groups and numbered, including control group(Group C) and treatment group(Group D). Three iodine-125 seeds(model 6711) were sealed in a transparent catheter to form a seeds strand. The general condition, body weight and survival time were monitored. MDCT examinations were performed every week for all animals and 3D MPR were acquired. The volumes of IVCTT were calculated. IVC, IVCTT and metastasis were examined with gross and histological pathology for both groups. The proliferating cell nuclear antigen (PCNA) index (PI) and apoptosis index(AI) of IVCTT were compared between two groups. T-test, Wilcoxon rank test and Kaplan-Meier survival curve analysis were used.Results:The success rate of operation was 100%. The body weight loss and the cachexia of Group C appeared earlier than Group D. At the third week, the body weight, the mean survival time, PI,AI in Group C and D were 2.03±0.13kg,31.67±5.28d,(63.01±2.01)%,(6.02±2.93)% and 2.23±0.12kg,45.83±8.68d,(16.73±5.18)%,(29.47±7.18)%, respectively. There were statistically significant difference between Group C and Group D (P< 0.05).The IVCTT volume of Group D was remarkably smaller than that of Group C (P< 0.05). Conclusion:The implantation of linear iodine-125 seeds strand is an effective method for treatment of IVCTT in rabbit model. It can inhibit the growth, promote apoptosis of IVCTT, and prolong the survival time of the rabbit with IVCTT.Part Two:Clinical ResearchTreatment of hepatocellular carcinoma with malignant inferior vena cava obstruction by implantation of linear iodine-125 seeds strand attached to IVC-stent combined with TACE:a clinical researchObjective:To evaluate the safty, feasibility and clinical efficacy of treatment of hepatocellular carcinoma with malignant inferior vena cava obstruction by the implantation of linear iodine-125 seeds strand attached to IVC-stent combined with TACE.Methods:From Mar 2009 to Jan 2010,32 patients of irresectable HCC with IVC obstruction were enrolled into this study. All of them received the implantation of 125I seeds strand attached to IVC-stent combined with TACE therapy. The postoperative complications were monitored. SPECT/CT was used to monitor the dose field distribution of iodine-125 seeds. The routine blood and liver function, diameter of obstructive segment of IVC, pressure gradient and clinical symptoms related to obstruction were compared before and after therapy. The stent patency rate and survival rate were calculated with Kaplan-Meier survival curve analysis. Cox proportional hazards model were used to analyze independent prognostic factors.Results:Technical successful rate was 100% for the implantation of 125I seeds strand attached to IVC-stent in the obstructive segment of IVC. A total of 36 stents were placed in 32 cases. Clinical improvements were remarkable after therapy. No severe complications related to the operation were observed, except the episode of acute renal dysfunction after therapy in one case, and acute pulmonary embolism in another one. SPECT/CT scan showed the dose field distribution of iodine-125 strands was a column with a radius about one centimeter which accompanied the stent. The diameter of obstructive segment of IVC, pressure gradient and clinical symptoms related to obstruction before and after operation were 6.70±5.66mm,18.58±4.64cmH2O,2.18±1.55 and 27.33±2.46mm,4.97±1.20cmH2O,0.42±0.61 respectively. There was statistically significant difference (P＜0.05). The cumulative stent patency rates and survival rates at 60,90,180,300 days were 100%,93.5%, 93.5%,83.2% and 100%,96.6%,67.7%,51.7%, respectively. Multinomial Logistic Regression revealed that tumor growth pattern and Child-Pugh classification were principal predictors of prognosis (P< 0.05).Conclusions:It is a safe and feasible therapeutic option for hepatocellular carcinoma with malignant IVC obstruction for the implantation of linear iodine-125 seeds strand attached to IVC-stent combined with TACE. And further study is needed for the long-term efficacy.