甲基丙烯酸羟乙酯共聚物液体栓塞剂栓塞兔肾VX2肿瘤可行性及有效性的实验研究

Transarterial embolization of renal VX2 tumors with liquid embolic agent poly 2-hydroxymethyl methacrylate-co-methyl methacrylate in a rabbit model

目的探讨甲基丙烯酸羟乙酯fHEMA）共聚物液体栓塞剂栓塞兔。肾VX2肿瘤的可行性及有效性。方法新西兰大白兔12只，应用CT引导下经皮穿刺组织块种植法制作兔。肾VX2肿瘤模型。肿瘤种植于右肾下极，肿瘤最大径至1．5cm行栓塞治疗。取1只肿瘤模型应用羰基铁粉标记的栓塞剂栓塞，用于测量栓塞剂可进入的肿瘤血管直径，术后即刻取材，行亚甲蓝及HE检查，余模型应用纯HEMA液体栓塞剂分别行超选择性栓塞及荷瘤肾整体栓塞。超选择栓塞组：微导管超选择进入肿瘤供血肾动脉分支内，将该动脉分支完全栓塞直至呈“铸型”改变；荷瘤肾整体栓塞组：将肾动脉及肾包膜动脉完全栓塞，直至肾动脉主干及肾包膜动脉呈铸型改变。术后即刻及1、3d行CT平扫，术后1、2、4、6周增强CT扫描观察栓塞剂及肿瘤变化。发现残余瘤再随访1周，处死取材。若术后观察6周无残余瘤及肺转移，则视为肿瘤完全栓塞坏死，处死取材，行病理学检查。结果成功造模11只，1只随访无肿瘤生长。血管内栓塞剂亚甲蓝染色呈蓝色，HE染色呈棕色，其可进人直径30～150μm的肿瘤血管，静脉端未发现栓塞剂。超选择栓塞组及荷瘤肾整体栓塞组各5只。术后即刻CT平扫，肿瘤周围区栓塞剂沉积明显；术后第1天肿瘤周围区密度降低，中心密度升高；第3天栓塞区与正常肾密度无差别，但出现肿胀改变。超选择栓塞组均发现残余瘤（2只术后1周、3只术后2周），位于交界区及肾包膜下；坏死区表现为凝固性坏死，与残余瘤分界清楚，大体标本显示肾包膜动脉参与残余瘤供血。荷瘤肾整体栓塞组术后观察6周无残余瘤及肺转移，大体标本示荷瘤肾萎缩，病理示肿瘤及邻近肿瘤的肾包膜完全凝固性坏死。结论HEMA共聚物液体栓塞剂能栓塞30～150μm的肿瘤血管，肾包膜动脉参与兔。肾VX2肿瘤供血，仅行肾动脉分支超选择栓塞难以使肿瘤完全坏死，应用该栓塞剂可将兔VX2肾肿瘤供血动脉及邻近正常动脉完全栓塞，使肿瘤完全凝固性坏死。

Objective To study the feasibility and effectiveness of liquid embolic agent HEMA-MMA in the arterial embolization therapy for the rabbit renal VX2 tumor models. Methods Renal VX2 tumor models were inoculated with the method of percutaneous CT-guided implantation of a small fragment of tumor into the inferior pole of the fight kidney and were embolized when the max diameter was 1.5 cm. One model was embolized with the mixture of HEMA-MMA and carbonyl iron powder and was harvested immediately after embolization, the sample was fixed by paraformaldehyde for histopathological examination with methylene blue staining and HE staining to demonstrate the sizes of the vessels that the HEMA-MMA could reach. The remaining models were treated with pure HEMA-MMA by superselective or nonselective embolization （SSE or NSE）. In SSE group, only the renal artery branch supplying the tumor was superselectively catheterized and embolized until the presence of ＂artery casting＂ change. In NSE group, the microcatheter was catheterized into the main renal artery then the whole renal artery branches and the renal capsular artery were embolized simultaneously until the presence of ＂artery casting＂ shape. Non-enhanced CT scans at immediate postoperation, on postoperative day 1 and day 3 were performed. The enhanced CT scans at the postoperative 1, 2,4 and 6 weeks were performed. Necrotic zone of the tumor was defined as non-enhancement in parenchyma phase, residual tumor was defined as delayed enhancement around the necrotic zone or obvious thickness and enhancement of the adjacent renal capsule. When detecting residual tumor, the model was followed up another 1 week and then harvested for histopathological examination, ff there was no residual tumor and lung metastasis in 6 weeks follow-up after operation, we defined this as complete necrosis and then harvested the kidney for histopathologieal examination. Results Eleven of the 12 rabbits were successfully inoculated VX2 tumors. The mixture of HEMA-MMA and carbonyl iron powder deposited in the arterial vessels demonstrated mazarine in methylene blue staining and brownness in HE staining. The diameter of the tumor vessels which the agent could reach was 30---150 μm, there was no embolic agent detected in the venous blood vessels. 5 models were performed with superselective embolization and the other 5 were embolized with nonselective embolization. The embolic agent demonstrated high density and obviously deposited in the surrounding zone of the tumor on immediate postoperative CT images, density of the surrounding zone decreased accompanied by density increase in the central area of the tumor on the first day postoperative CT images, Density difference between the embolism zone and normal renal tissue disappeared on the third day postoperative CT images aeeompanied by swelling changes of the embolized area. Residual tumor was detected in all 5 superselectively treated cases （2 in 1 week, 3 in 2 weeks）, which located in the area of junctional zone and subrenal capsule. The necrotic zone was demonstrated coagulative necrosis on histopathologic images, the boundary between the residual tumor and the necrotic zone was clearly showed both on histopathologic images and gross specimen. Renal capsular artery participating in the residual tumor blood supply was also shown on gross specimen. There was no residual tumor and lung metastasis detected in nonselective treated group during the period of 6 weeks follow-up. Atrophy of the whole tumor-burdened kidney was shown on gross specimen and complete coagulative necrosis of the total tumor and the renal capsule adjacent to the tumor was demonstrated on histopathologie images. Conclusions Liquid embolic agent HEMA-MMA can embolize tumor blood vessels with a diameter of 30--150 μm. The renal capsular artery participates in the blood supply of the VX2 kidney tumor, so only superselective embolization of the renal artery branch with this liquid embolic agent may not induce the whole necrosis of the tumor, but complete necrosis of the tumor can be obtained by embolizing of all the tumor vessels and the adjacent normal renal arteries with this liquid embolic agent.