Study On The Feasibility And Availability Of HEMA Copolymer Liquid Embolism Agent (Co-HEMA) Embolization Of Rabbit VX2 Liver And Kidney Tumors

Objective To study the feasibility, safety and effect of transarterial embolization for solid organs with copolymer liquid embolic agent HEMA in rabbit kidneys. Method For 6 New Zealand white rabbits, unilateral kidney was embolized transarterially with HEMA via 3 types of microcatheters. Angiography was done at follow-up to observe if there was vascular recanalization, and CT scan was performed to observe the deposition of HEMA and the morphagical changes of the embolized kidney. Histopathological changes of intravascular and the surrounding tissues were observed under microscope. Results Unilateral kidneys of all the 6 rabbits were embolized successfully,3 kidneys were studied in the acute phase (1-3 day after embolization) and the other 3 were observed in the chronic stage(8 weeks or 12 weeks after embolization). There was no catheter gluing and the internal surfaces of the microcatheters were still smooth after embolization. Satisfing deposition of HEMA was observed in the kidneys and there was no angiographic recanalization at follow-up. There was no vascular intima necrosis found in acute phase and a large number of neutrophils and monocytes infiltration was observed in the vessels, focal necrosis of glomerular and renal tubular was also found in this period. In chronic stage, the changes of glomerular and renal tubular were atrophy, fibrosis and hyaline degenerations. Conclusions Copolymer liquid embolic agent HEMA has the property of radiopacity, low viscosity, without catheter gluing, compatible with common commercially available microcatheters, better biocompatibility, and no angiographic recanalization at follow-up. It is suitable for solid organ embolization.Objective To modify the inoculation method of rabbit VX2 liver and kidney tumors with the technique of "One step, Preloaded in vitro and Traced in vivo" under computer tomography (CT) guidance and to create a new tumor-burdened rabbit model with the method of inoculating the tumor tissue into the subcutaneous fascia of the rabbit back. Method Equipments utilized in this method contained 16-gauge thoracic-puncture needle as the introducer needle(16G,8.5cm),18-gauge Co-Axial Introducer Needle with the smoothed and blunted tip as the stylet, strips of absorbable gelatin sponge with the size of 1.5mm* 1.5mm*3.0mm. A marker was done at the the tail part of the stylet where the length was 1cm longer than that of the 16-gauge introducer needle (9.5cm). The fresh tumor tissue was cut into the long strip shape with the size of 1.0mm*1.0mm*3.0mm. The absorbable gelatin sponge strip and the fresh tumor strip were all loaded from the tip part of the 16-gauge introducer needle. First, one strip of absorbable gelatin sponge was rolling compressed and then loaded into the the cavity of the introducer needle, then 0.3 ml contrast agent was injected into the cavity to immerge the gelatin sponge, the third step, one strip of tumor tissue was loaded into the cavity, at last, the tip part of the introducer needle was wiped with one piece of sterile saline gauze for about 5 to 10 times. The procedure of "tissue preload" was completed. The recipient rabbits were anesthetized by injection of 3% pentobarbital sodium (1 ml/kg) from the marginal ear vein, implantation site was set in the lateral segment of the left liver lobe and the inferior pole of the kidney. Rabbits were in supine position in VX2 liver tumor implantation and in prone position in VX2 kidney tumor implantation. CT scan was done to perform the puncture route of the introducer needle, skin of the puncture site was disinfected and incised about 0.5mm, then the "preload" introducer needle was punctured according to the designed route with the method of "step by step" under CT guidance. After targeted site was achieved, from the tail part of the introducer needle, the stylet was inserted till to the marker on it. About 5s later the introducer needle and the stylet were slowly and simultaneously pull out. The puncture site was manually pressed about 30-60s, CT scan was performed to show the immediate implantation site. CECT scans were performed 2 weeks,3 weeks and 4 weeks later to show whether the models were successfully inoculated and to monitor the growth of the inoculated tumors. Subcutaneous fascia tumor-burdened rabbit model was experimently inoculated in two rabbits. The subcutaneous fascia on the back was the implantation site. Two pieces of tumor tissue with the size of 1.0mm*1.0mm*3.0mm was inserted into the nipple cavity of the 10 ml syringe which contained 3 ml sterile saline, then a 20ml syringe needle (18G,38mm) was connected to the nipple of the 10 ml syringe and the the tumor fragments were injected into the subcutaneous fascia of the rabbit back. Ten days later palpation was done at the inoculated site to show whether the tumor was successfully inoculated. Results Immediate implantation site was demonstrated high density nodular in the liver or kidney parenchyma on plain CT images. Ten rabbits underwent VX2 liver tumor implantation and twelve rabbits underwent VX2 kidney tumor implantation, successful tumor growth rate was 100%(10/10) and 91.67%(11/12) respectively. All the inoculated tumors were mono nodular, there was no tract and perihepatic or perinephric seeding occurred during the follow up. Growth sites of the tumors were all basically corresponding to the immediate implantation sites showed on immediate postoperative CT images. The two rabbits were all successfully inoculated tumors in the subcutaneous fascia on the back. Two weeks later subcutaneous nodule could be palpated at the implantation site, the inoculated tumor obviously grew up at 3 weeks and could be resected integrally from the subcutaneous fascia and the neighbour muscles. Gross specimen showed that the the tumor had smooth surface, pliable quality and less necrosis in the central part. After harvested, the 2 rabbits could have a healthy survival and no metastasis occurred during the 3 to 4 weeks follow up. Conclusions Inoculation of rabbit VX2 liver and kidney tumors with the technique of "One step, Preloaded in vitro and Traced in vivo" under computer tomography (CT) guidance has the advantages of convenient, immediate confirmation of the implantation site, high successful tumor growth rate and no tract seeding. Subcutaneous fascia tumor-burdened rabbit model may be successfully inoculated with the method of subcutaneous tumor tissue injection. Tumors harvested from this model have the quality of pliable and less necrosis in the central part, so they are the ideal tumor sources for tissue fragment inoculation. Subcutaneous fascia tumor-burdened rabbit may suffer less injury induced by harvest and could healthily survive for a long time after harvest.Objective To evaluate the feasibility of saphenous artery as an artery access for embolization therapy of rabbit VX2 liver and renal tumors and to explore the substitutional ability of saphenous artery for femoral artery as a routine artery access for rabbit vascular interventional therapy. Method 24 rabbit VX2 liver and renal cancer models were performed arterial embolization in group A, trans-femoral artery access (n=8) and in group B, trans-saphenous artery approach (n=16). Body surface anatomy and the variation of the saphenous artery were observed and recorded. Equipments and operational methods of the two artery approaches were the same. First, after anesthetization the target artery (femoral or saphenous artery) was separated and was punctured by a 22G intravenous cannula, then the needle of the cannula was removed and the 0.018 inch microwire was inserted through the cannula till to the lower abdominal aorta, then the cannula was removed, along with the microwire, the 5 F micropuncture sheath was rationally inserted, at last, a hemostasis valve was connected to the sheath. The processes of artery separation and sheath insertion were completed. Diameters of the saphenous artery, femoral artery and the iliac artery were measured and recorded on the angiography images. Time needed for artery separation, time needed for sheath insertion, success rate of sheath insertion, the inserted length of the sheath, infection rate of incision and limping incidence of the two groups were recorded and compared. Time needed for artery separation was defined as the time needed for the process from disinfection of the incision to the successful artery separation and two sutures was successfully layed under separated artery. Time needed for sheath insertion was defined as the time needed for the process from puncture of the artery to successful insertion and fixation of the sheath. Results Saphenous artery was obviously observed on the body surface in 91.67%(22/24) rabbits. Sheathes were all successfully inserted in the two groups. Time needed for artery separation, inserted length of the sheath, infection rate of the incision, limping incidence on postoperative day 7 and day 14 were (367.30±37.30) s vs (978.20±156.30) s, (20.20±2.60) mm vs (58.60±9.50) mm,0 vs 37.50%,6.25% vs 62.50%,0 vs 25% respectively. The differences of these 5 contrasting data were all statistically significant. Time needed for sheath insertion and limping incidence on postoperative day 1 were (42.80±9.90) s vs (43.60±7.0)s (p>0.05) and 70% vs 100% (p>0.05) respectively. Diameter of the saphenous artery, superficial femoral artery, common femoral artery, external iliac artery and common iliac artery was (1.29±0.12) mm, (1.91±0.27) mm, (2.18±0.15) mm, (2.22±0.13) mm and (2.39±0.15) mm respectively. Conclusions Saphenous artery access is a wonderful arterial approach for rabbit VX2 liver and renal tumor embolization, this artery access has the advantages of superficial location, low variability, suitable for insertion of 5F micro sheath, time saving, convenient and much less invasive for sheath insertion. For most of the rabbits, transsaphenous access may substitute femoral approach as the route artery access for rabbit vascular interventional therapy.Objective To study the feasibility and efficiency of liquid embolic agent HEMA-MMA in the arterial embolization therapy for VX2 rabbit renal tumors. Method VX2 renal tumor models were inoculated with the method of "One step, Preloaded in vitro and Traced in vivo" under the CT-guidance and were performed embolization therapy 3 weeks later. One tumor model was embolized with HEMA-MMA traced with carbonyl iron powder and was harvested immediately after embolization, the whole tumor-burdened kidney was fixed by paraformaldehyde and histopathological examination with methylene blue staining and HE staining was performed to observe the vessels embolized by HEMA-MMA in the normal kidney and tumor tissues. The other models were treated by superselective or nonsuperselective embolization. In nonsuperselective embolization group, the whole artery branches and the renal capsular artery of the tumor-burdened kidney were all simultaneously embolized. Plain CT scans were performed at the time of immediate postoperation, on postoperative day 1 and day 3 to show the changes of the HEMA-MMA. Enhanced CT scans were done at the time of postoperative 1 week,2 weeks and 6 weeks to show the changes of the tumors and the kidneys. The rabbit was sacrificed when the metastasis was detected and histopathological examination was performed to show the changes of tumor. Results 11 of the 12 rabbits were successfully inoculated VX2 tumors in the inferior pole of the right kidneys. HEMA-MMA mixed with carbonyl iron powder was demonstrated mazarine on methylene blue staining images and brownness or yellow-brown on HE staining images. Arteries with the diameters of 30-150μm could be embolized by HEMA-MMA, embolization agent was not detected in the venous blood vessels. Five models were treated by superslective renal artery embolization and the other five were treated by nonsuperslective embolization. On immediate postoperative CT images, HEMA-MMA was showed high density and mainly deposited in the surrounding zone of the tumor. On day 1 postoperative CT images, density of the surrounding zone decreased while the central part of the tumor increased. On day 3 postoperative CT images, density difference between the embolism area and normal renal disappeared and the change of swelling was demonstrated. For cases in superselective embolizaton, the embolized area was showed nonenhancement zone on enhanced CT images performed at the postoperative week 1 and week 2. The residual active tumor were all detected in those five cases which mainly located in junctional zone and the subrenal capsule. The capsular artery originating from the main artery trunk of the kidney was the main feeding artery of the residual tumor. For the five cases with non superslective embolization, no enhancement was showed on CT images and there was no residual tumor and lung metastases detected during 6 weeks follow up. The volume of the embolized kidney was decreased. Complete coagulative necrosis of the tumor and the renal capsule was showed on histopathologic images.Conclusions Vessels with the diameter of 30-150μm may be embolized by the liquid embolic agent HEMA-MMA, complete necrosis of the VX2 kidney tumor may be achieved with the method of cast embolization of all the tumor vessels and the adjacent normal renal arteries, so embolization with HEMA-MMA is a feasible and effective method for the treatment of VX2 kidney tumor.Objective To study the feasibility and efficiency of liquid embolic agent HEMA-MMA in the arterial embolization therapy for rabbit VX2 liver tumors. Method 16 rabbits with successfully inoculated VX2 liver tumor were divided into group A, group B and group C. One VX2 liver tumor was underwent embolization with HEMA-MMA traced with carbonyl iron powder, after immediate postoperative CT examination the tumor was harvested to show the diameters of the vessels embolized by HEMA-MMA. Five rabbits in group A with the max diameter≤1.5cm and five rabbits in group B with the max diameter≥1.5cm were performed hepatic artery embolization respectively. Follow-up with plain and enhanced CT scan was performed, changes of liver function were also recorded. The other 5 rabbits in group C were as control cases to investigate the natural prognosis of VX2 liver tumors. The curative embolization was defined as no metastatic lesions found in the lung and/or liver during the 6 weeks postoperative follow up, then the the rabbit was sacrificed. If metastatic lesions were found in group A and in group B, the rabbit was followed up to death, then the tumor was harvested. Histopathological examination with HE staining was done to show the changes of the tumor. Results HEMA-MMA traced with carbonyl iron powder was demonstrated mazarine on methylene blue staining images and brownness or yellow-brown on HE staining images. Arteries with the diameters of 30-300μm could be embolized by HEMA-MMA. In group A, HEMA-MMA deposited in the peripheral zone of the tumor and showed high density on immediate postoperative CT images. On day 1 postoperative CT images, the density of the peripheral zone of the tumor was decreased while the central region was increased. On day 3 CT images, swollen change of the tumor was demonstrated and the whole density of the tumor was decreased and lower than the normal liver tissue.3 cases in group A were achieved curative embolization which was mainly showed shrink and calcification changes of the tumor on the follow-up CT images. Metastatic lesions were found in the other 2 rabbits but the embolized lesion in the liver was also showed shrink and calcification. The overall survival in group A was (49.2±12.2) d. Total necrosis of the tumor and the organization tissue enveloping the necrosis zone were found on histopathological images. HEMA-MMA was found in the necrosis zone and the organization tissues which was showed brownness or yellow-brown on HE staining images. In group B, changes of HEMA-MMA on postoperative CT images were similar with those of in group A. Metastatic lesions in the lung or the liver or the celiac lymph node were found in those 5 cases during 1 week postoperative follow up. The overall survival in group B was (35.4±3.7) d. Residual active tumors were found in the peripheral zone of the tumor, boundary between the residual tumor and the necrosis part induced by HEMA-MMA embolization was clearly showed on HE staining images, the necrosis zone induced by HEMA-MMA embolization was mainly manifested coagulative necrosis with the character of intact contour preservation of the tumor cells and tumor nodular. Liver enzymes increased and gradually declined during the observation period. Metastatic lesions were all found in the 5 cases in group C, cachexia phenomenon such as anorexia, emaciation and lipsotrichia were gradually appeared in the end stage. The overall survival in group C was (34.8±6.3) d. Conclusions Tumor arteries with the diameter of 30-300μm may be embolized by liquid embolic agent HEMA-MMA and then induce the necrosis of the tumor. For smaller liver tumors with abundant blood supply, transarterial embolization with HEMA-MMA may achieve curative therapy. For larger VX2 liver tumors, palliative embolization with HEMA-MMA is also may performed to achieve partial necrosis and to decrease tumor loads, so embolization with HEMA-MMA is a feasible and effective method for the treatment of tumor.