化学冷冻消融过程中肿瘤边缘药物适形分布的实验研究

发布时间：2018-02-05 04:28

本文关键词： VX2肿瘤化学消融冷冻消融　出处：《中国人民解放军医学院》2014年硕士论文　论文类型：学位论文

【摘要】：目的通过对兔VX2背部肿瘤模型进行化学冷冻消融，观察化学冷冻消融过程中肿瘤边缘药物的空间分布情况，研究冰球对药物适形分布的动力学作用，探讨化学冷冻消融在灭活边缘残余肿瘤方面相对于单纯化学消融及冷冻消融的优势，为消融毗邻重要脏器的肿瘤提供临床应用的理论依据。材料和方法选取新西兰大白兔32只，4只用于肿瘤兔，待接种肿瘤大小为2-3cm时，CT引导下采用穿刺活检法将肿瘤兔内的肿瘤组织接种到28只兔的双侧背部肌肉内。每周行CT增强扫描，观察肿瘤的存活率、大小、接种部位的满意度及影像学表现。3周后选取双侧肿瘤接种部位较满意，形状较规则且直径为2.0-2.5cm的肿瘤兔24只。并将其背部的48个孤立的肿瘤随机分为A/B/C/D四组。A组为对照组（CN）：不做任何处理；B组为单纯化学消融组(CH)：1.4mg盐酸表柔比星、200ul无水乙醇、1ml碘佛醇、300ul亚甲蓝及1ml生理盐水混匀后缓慢注入肿瘤边缘，分5次注射，每次注射后立即行CT扫描观察药物的分布情况；C组为单纯冷冻消融组(CA)：将冷冻探针定位于肿瘤中央后，进行冷冻，CT扫描观察冰球达肿瘤外侧边缘后，间隔3min继续冷冻2min，共重复5次；D组为化学冷冻消融组(CH-CA)：麻醉针定位于肿瘤边缘后，将冷冻探针垂直穿刺至制冷点距麻醉针针尖5-10mm处，然后冷冻，CT扫描观察冰球边缘达麻醉针针尖后，冷冻1min后，将混合液注入，继续冷冻30s后CT扫描观察药物分布，间隔3min后以同样的方法，共分5次注射完。四组分别于术后1h、3d、7d、10d将肿瘤兔处死，每次6只。其中第3d、7d、10d处死前行CT增强扫描，观察肿瘤边缘的影像学特征及处死后的大体标本、病理切片，评价肿瘤的坏死情况。结果 A组：术中CT增强可见明显环形强化。术后（1）1h：CT平扫可见低密度圆形或椭圆形肿块影；大体标本可见肿瘤边缘呈鱼肉状，肿瘤中心液化坏死；病理低倍镜下组织内多灶浸润性癌巢，高倍镜下癌细胞呈条索状或腺样排列，异型明显并可见核分裂象。（2）3d、7d、10d：肿瘤逐渐增大，余表现同前。 B组：术中可见注入高密度混合物后，仅有少量药物局限在肿瘤边缘，大部分药物弥散至肿瘤中央。术后（1）1h：CT扫描可见肿瘤边缘及中心均可见高密度造影剂；大体标本可见肿瘤中央液化坏死，淡蓝色坏死物流出，肿瘤边缘呈淡蓝色改变；病理改变同对照组。（2）3d、7d、10d：肿瘤逐渐增大，第3天CT平扫可见肿瘤中央少量高密度影，第7、10天高密度影完全消失，增强扫描均显示肿瘤呈环形强化；病理切片显示肌纤维细胞与肿瘤细胞临界处仅可见少量的肿瘤细胞核碎裂及核溶解。余大体标本及病理改变同术后1h。 C组：术中可见低密度冰球形成。术后1h、3d、7d、10d：CT平扫可见肿瘤呈低密度影，，增强后显示肿瘤上边缘未见强化，环形强化出现缺口；大体标本可见血性坏死物流出，肿瘤上边缘可见深红色的冻伤组织，余表现同对照组；病理组织切片显示，肌纤维细胞受到破坏，但仍有大量的肿瘤细胞。 D组：术中可见低密度冰球边缘有弧形高密度影。术后（1）1h：肿瘤上边缘可见深红色的冻伤组织，余大体标本及病理同B组表现。（2）3d、7d、10d：CT增强扫描显示肿瘤上边缘同C组，下边缘环形强化出现缺口并逐渐增大。大体标本可见肿瘤边缘呈不连续的鱼肉状改变，上缺口处呈冻伤表现，下缺口处呈坏死表现。病理切片显示，坏死侧可见大量肿瘤细胞轮廓消失，核碎裂及核溶解，细胞浆崩解，呈均质状；肿瘤存活侧可见大量肿瘤细胞浸润。结论（1）兔背部VX2肿瘤模型采用经皮穿刺活检法种植肿瘤，方法简单，成功率高，肿瘤形状较规则，具有较好的实验重复性。（2）化学冷冻消融对混合的药物具有适形分布的作用，可延长药物与病变边缘肿瘤细胞的作用时间，较单纯化学消融及冷冻消融灭活边缘肿瘤细胞具有明显的优势。
[Abstract]:objective
Through chemical freezing of rabbit VX2 tumor model of back ablation, the spatial distribution of the edge of tumor drug observation chemical cryoablation in the process of research of ice hockey conformal dynamical effects on the distribution of chemical drugs, cryoablation compared with chemical ablation and cryoablation advantage in the inactivated edge of residual tumor, and provide a theoretical basis for clinical application. For the adjacent important organs. Tumor ablation
Materials and methods
32 New Zealand white rabbits were selected, 4 for tumors of rabbits, when the tumor size is 2-3cm, CT guided biopsy method using tumor rabbit within tumor tissue of 28 rabbits were inoculated into the back muscles. Weekly enhanced CT scanning, survival rate, tumor size,.3 week satisfaction after studying and imaging the vaccination site selection bilateral tumor inoculation site was satisfactory, with regular shape and the diameter of tumor was 2.0-2.5cm. 24 rabbits and the back of the 48 isolated tumor were randomly divided into four groups A/B/C/D group.A as control group (CN): no treatment; group B simple chemical ablation group:1.4mg (CH) epirubicin hydrochloride, 200ul ethanol, 1ml ioversol 300ul, methylene blue and 1ml saline after mixing slowly injected into the tumor edge, 5 doses, CT scanning was performed to observe the distribution of drugs immediately after each injection; group C was simply frozen fire Financial group (CA): the frozen probe located in tumor central, frozen, CT scan were up to the outer edge of tumor hockey after the interval of 3min continue to freeze 2min, repeat 5 times; D Group Chemical cryoablation group (CH-CA): anesthesia needle located in tumor edge, the cryoprobe puncture vertically to refrigeration anesthesia needle at 5-10mm point, and then frozen, CT observed the anesthesia needle after the edge of the ice, frozen 1min, mixed liquid injection, to freeze after 30s CT observed the drug distribution, after an interval of 3min in the same way, is divided into 5 injection end. Four groups were in the postoperative 1H. 3D, 7d, 10d tumor rabbits were sacrificed, each time 6. The 3D, 7d, 10d were underwent CT enhanced scan, morphological characteristics and death observation of tumor edge image after specimens, pathology, tumor necrosis evaluation.
Result
Group A: intraoperative CT showed obvious enhancement of annular enhancement. (1) postoperative 1h:CT scan showed low density round or oval mass; the gross specimen showed the tumor margin was fish shape, tumor pathological center necrosis; low magnification in multifocal invasive cancer nests, cancer cells under the microscope showed high times cords or glandularly arranged, shaped obvious and visible mitotic. (2) 3D, 7d, 10d: the tumor gradually increased, with more than performance.
B group: surgery can be seen into the high density mixture, only a small amount of drugs limited in tumor edge, most of the drug diffusion into the tumor (1). The postoperative 1h:CT scanning edge and center of visible tumors showed a high density contrast agent; tumor specimens visible central necrosis, pale blue necrosis of the logistics, the edge of tumor was pale blue change; the pathological changes of the control group. (2) 3D, 7d, 10d, tumor increase gradually, third days CT scan shows a small amount of high density central tumor, the 7,10 high density shadow disappeared, enhanced scan showed that the tumors were ring enhancement; Pathology showed the muscle cells and tumor cells at the critical point there are only small number of tumor nuclei fragmentation and nuclear dissolution. Gross and pathological changes with 1h. after operation
Group C: visible low density hockey formation during the operation. Postoperative 1H, 3D, 7d, 10d:CT scan showed that the tumor showed a low density, enhanced tumor showed no enhancement edge, ring enhancement gap; the gross specimen showed ischemic necrosis on the edge of the visible tumor logistics, deep red frozen tissue, copresented the same as the control group; the pathological tissue sections showed that muscle cells are damaged, but there are still a large number of tumor cells.
D group was visible in the low density ice hockey edge arc high density. After the operation (1) 1H: the edge of the visible dark red frostbite tissue tumors, more than the gross specimen and pathology with the B group. (2) 3D, 7d, 10d:CT scan showed the tumor edge with the C group, under the edge of the ring strengthen the gap and increases gradually. The gross specimen showed the tumor margin was not continuous fish shape change, on the gap is the gap under the frostbite, showed necrosis. Pathology showed necrosis, tumor cells showed a large number of side profile disappeared, nuclear fragmentation and karyolysis, cytoplasm disintegration, homogeneous tumor survival; the side shows a large number of tumor cell infiltration. Conclusion
(1) rabbit back VX2 tumor model using percutaneous biopsy of the tumor, the method is simple, high success rate, tumor shape is regular, good repeatability. (2) chemical conformal cryoablation distribution of the role of the mixed drugs have effect, can prolong the time of drug and lesion edge of tumor cells, compared with simple chemical ablation and cryoablation inactivated tumor cell edge has obvious advantages.

【学位授予单位】：中国人民解放军医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R73-36

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