| BacgroundThe operation rate of primary liver cancer was only8%-25%. After transcatheter arterial chemoembolization, most patients recurred for the reason of collateral circulation after1-3months of stable illness state. Liver cancer was not sensitive to external radiation. The dose of radical cure was farly higher than the tolerance dose of the whole liver. The implantation of I25â… seed was a method of the implantation of the radioactive source to tumor or the nearby infiltrated organization (including lymph draining area), which can kill tumor cancer by the emitting ray. It can implant intraoperatively or punctured by the help of imaging. This therapy can choose the need area of radiation; the tumor cell was radiated by the ray during a long time. The tumor got a high dose of radiation, while the surrounding cell got a low dose of radiation. This study was about to study the therapy effect and clinical value which by check the damage to the tumor cell and irradiation extent after implantation of125â… seed on the rabbit VX2liver cancer model. The study content was divided into the following two parts.PART â… Experimental research on the treatment of VX21iver cancer in rabbits with125â… seeds implantationObjective To evaluate the therapeutic effect and the influence to the surrounding liver of125â… seeds on the rabbit VX2model by the way of99mTc-MIBI imaging, CT and ultrasound to check the growth of the tumor, blood supply and the therapy affect and to provide experimental basis for clinical application of125â… seeds implantation.Methods Twelve VX2liver cancer models made from New Zealand rabbits were divided into two groups, a therapy group and a control group.125â… odine seeds and dummy seeds were implanted into the tumors. Before the implantation and at7,14,28and60d after implantation, The following check was done.(1)99mTc-MIBI imaging to measure the counts of the tumor(T) and the normal liver cancer by the technique of the region of interest to calculate the ratio of T/N,the early ratio of the ratio of T/N(ER),the delayed the ratio of T/N(DR) and the retention index.(2) CT-enhanced scanning to study the tumor volume,the tumor growth rate and the changes of the surrounding normal liver.(3) Two dimension ultrasound to check the tumor size and the blood supply. The standard of blood flow grade:0grade:no blood signal inside the tumor; â… grade:1-2punctiform blood flow inside the tumor, the blood vessel diameter <1mm;â…¡ grade:1main blood vessel inside the tumor and the blood vessel distribution less than the tumor radius.â…¢ grade:more than4strip of blood vessel inside the tumor or interconnection of blood vessel inside the tumor (4) hepatic function examination including Alanine Aminotransferase, ALT and aspartate amino transferase, AST. Pathological study of tumor and normal liver was done to evaluate the damage caused by125â… seeds.Results (1) Animal living stste Before the implantation the movement condition,food intake,and the mental status of the therapy rabbit was similar to the normal rabbit. At28day after implantation, the extent of the exhaustion in the rabbits of the control group was more serious and3rabbits died. The state of therapy group was better than the control group, and no died rabbit in the therapy group.(2) The changes of CT imaging In therapy group:the edge enhancement was gradually thinner during28days after therapy, some enhancement disappeared.The125â… seed gathered to the tumor center, no liver metastasis was found. The maximum and the minimum diameters were both measured at the CT arterial phase. In control group:The volume of tumor was gradually enlargement. In control group:The volume of tumor was enlargement at7days after implantation, whereas guadully smaller at14-28days after implantation.Before implantation there was no significance of the tumor volume in the two groups, while the therapy group was less than the control group at7,14,28and60d after implantation. The self contrast in the therapy group, the tumor volume was enlarged in the early time and decreased lately. At before implantation to7d,7-14d,14-28d the value of t was7.78,7.23,6.48,6.78, the difference was significantly. The self contrast in the control group, the tumor volume was gradually enlarged, At the stage of before implantation to7d,7-14d,14-28d after implantation, the value of t was9.83,8.65,7.58,7.53, the difference was significantly. Changes of the tumor growth rate between the control group and the therapy group:There was no difference in the growth rate of the two groups after7days of1251seed implantation, While the difference was significant at14d and28d after implantation.(3) The changes of semiquantitative index in the99mTc-MIBI imaging IN control group,there was no change of T/N ratio,ER and DR during different time after125â… seed implantation. In therapy group, the value of ER and DR was gradually decreased after125â… seed implantation. Before implantation to7d,7-14d,14-28d after implantation, the value of t was5.37,7.85,7.63,6.89, the difference was significantly. There was no significant difference of RI at all observation time stage between the therapy group and the control group. There was no significant difference of RI of the self contrast in both the control group and the therapy group at the stage of before implantation to7d,7-14d,14-28d after implantation (P>0.05).(4) Characterastic of CDFI After4-6weeks of tumor implantation(2-4weeks of seed implantation), strip thickly blood signal can be found about â…¡,â…¢ grade in the control group. While punctiform blood signal can be found about â… ,â…¡ grade in the therapy group.The volum of tumor was gradually larger in the control group, while smaller in the therapy control.(5) Pathological findings In control group, the growth of tumor cell was very prosperious. There was a great guantity of compact disposed tumor cell under the microscope. The construction of the tumor cell was like trab,nest. The cellur nuclus was large,darking-stained,rich of heteromorphism and nuclear division,obvious of nucleoli. A small quantity of tumor giant cells could also be found. In therapy group, after28days seed implantation, most tumor cell around the seed was of cataplasia and necrosis. The closer to the seed the worse of necrosis.(6) The changes of liver function index There was no difference of both ALT and AST value before125â… seed implantation. After14-28d of implantation, the ALT value of the therapy group was lower than the control group. While7-28d of implantation, the AST value of the therapy group was lower than the control group. Both of Alt and AST increased gradually in the control group.Conclusion:1. The rabbit VX2liver cancer model was similar to the humor primirary huge liver, which was an ideal liver experimental model. The diameter of the tumor was about2cm after2weeks of cell implantation in the rabbit model by the means of cellullar suspension. The tumor in this period was all mono-produced, which could be therapied ideally analoge to the humor liver cancer. It was the best time of the125â… seed implantation.2. It was verified by the experiment that brachytherapy with125â… seeds was effective whichc ould significantly inhibit tumor grow and it was a safe technique with less complication.3. The99mTc-MIBI imaging could find the changes of not only the volume of the tumor but also the function and the metabolic activity of the tumor cell. There was great application value in the evaluation of the effect of the rabbit VX2liver cancer treated by the125â… seed implantation by this technique. The value of T/N ratio had nothing to do with tumor diameter but related with the blood flow and the state of metabolism of the tumor.4. Ultrasonograph was a noninvasive checking thchnique. It wasnot affected by the tissue overlapping and could examin the condition of the tumor vassular, especially the minute blood vessel and bent blood vessel.5. CT could clearly display the location of the seed,identify the relationship of the radioactive seed and the surrounding organ. During the recheck of the post implantation, CT conduced to get the message of the locatation of the seed, but was difficult to the activity of the tumor.6.125â… seed implantation could effectively kill and wound the tumor,which had slightly damage to the surrounding liver.This finding provided reliable experimental base of the clinical application of treatment of liver cancer with the1251seed implantation. PART â…¡ Experimental research on the liver radiation damage by the implantation of125â… seeds. Objective To study the pathological changes and to reserve the dynamic state of radiation injury of the liver during different period after125â… seed implantation to the liver, and to explore the relationship between the time and the dose of the radiation injury after the implantation of125â… seed to the rabbit liver, and then to provide the theoretical basis of the diagnosis and prevention of the liver injury.Methods:20rabbits were divided into A,B,C,D groups completely randomly. Every group had5rabbits.3seeds were implanted in every rabbit liver. They were implanted different dose of125â… seeds. A:1.0mCi, B:0.7mCi, C:0.4mCi and D group as control group were implanted dumb seed. These rabbits were studied the following index:â‘ general state of health.â‘¡hepatic function and blood routine examination post-operation of two weeks, one month and two months.â‘¢CT and pathological examinations were carried out.Results:(1) less food intake, more water drinking,less acting, higher temperature after2weeks of operation, obviously in group A. their food intake can recover in1month and their weight were not lessened in2month. There was no death case.(2) There was no ionizational liver injury of the CT appearance of low density.(3) Pathlogical findings After2weeks of implantation, distension and hyperemia were found in hepatic sinusoid; a great quantity of inflammatory cell infiltrated at the header area; hepatic cord arranged disorder; small vessels and central venous was found dilatation and hyperemia, which was obvious in group A. However fiber hyperplasia was not found. After1month of implantation, liver cell swelled slightly hepatic cord arranged regulatly, inflammatory cell desreased in the area of the header and hepatic sinusoid, all typical in group A. There were no changes in central veins and small vessels in the area of header. Fibroplasia was not found. After2months of implantation, liver cell swelled highly to submit the appearance of balloon, slightly phlebostenosis and eosinophilic body was found, a great quantity of inflammatory cell infiltrated at the area of the header and the hepatic sinusoid, all typical in group A and B. In addition, Fibroplasia was found in the area of both Kiernan's space and the header, which caused widen the interlobular septum in group A, wheras which happened in the area of peripheral zone of small vessels in group B, No obvious fibroplasia was found in group C.(4) Changes of liver function and routine blood test Both ALT and AST were lightly heighten about2times after operation, obviously30days after operation, but they all gradually dropped, which recovered to the preoperative level about2month after operation. GGT and white blood cell were lightly heighten about1.5and2times after operation, obviously2weeks after operation, but they all gradually dropped, which recovered to the preoperative level about2month after operation.Conclusion:1. The value of ALT,AST,GGT and white blood cell heightened slightly after seed implantation, obviously after2weeks implantation, then gradually falled off30days later, and on the whole recovered to the level of preoperation2months later.2.Dose of0.7mCi and0.4mCi had lightly injury to the liver, while the dose of1.0mCi could injure the local liver tissue. Therefore, the activity of every1251seed should not surpass1.0mci clinically.
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