本文關(guān)鍵詞： VX2腫瘤 化學消融 冷凍消融　出處：《中國人民解放軍醫(yī)學院》2014年碩士論文　論文類型：學位論文

【摘要】：目的 通過對兔VX2背部腫瘤模型進行化學冷凍消融，觀察化學冷凍消融過程中腫瘤邊緣藥物的空間分布情況，研究冰球?qū)λ幬镞m形分布的動力學作用，探討化學冷凍消融在滅活邊緣殘余腫瘤方面相對于單純化學消融及冷凍消融的優(yōu)勢，為消融毗鄰重要臟器的腫瘤提供臨床應用的理論依據(jù)。 材料和方法 選取新西蘭大白兔32只，4只用于腫瘤兔，待接種腫瘤大小為2-3cm時，CT引導下采用穿刺活檢法將腫瘤兔內(nèi)的腫瘤組織接種到28只兔的雙側(cè)背部肌肉內(nèi)。每周行CT增強掃描，觀察腫瘤的存活率、大小、接種部位的滿意度及影像學表現(xiàn)。3周后選取雙側(cè)腫瘤接種部位較滿意，形狀較規(guī)則且直徑為2.0-2.5cm的腫瘤兔24只。并將其背部的48個孤立的腫瘤隨機分為A/B/C/D四組。A組為對照組（CN）：不做任何處理；B組為單純化學消融組(CH)：1.4mg鹽酸表柔比星、200ul無水乙醇、1ml碘佛醇、300ul亞甲藍及1ml生理鹽水混勻后緩慢注入腫瘤邊緣，分5次注射，每次注射后立即行CT掃描觀察藥物的分布情況；C組為單純冷凍消融組(CA)：將冷凍探針定位于腫瘤中央后，進行冷凍，CT掃描觀察冰球達腫瘤外側(cè)邊緣后，間隔3min繼續(xù)冷凍2min，共重復5次；D組為化學冷凍消融組(CH-CA)：麻醉針定位于腫瘤邊緣后，將冷凍探針垂直穿刺至制冷點距麻醉針針尖5-10mm處，然后冷凍，CT掃描觀察冰球邊緣達麻醉針針尖后，冷凍1min后，將混合液注入，繼續(xù)冷凍30s后CT掃描觀察藥物分布，間隔3min后以同樣的方法，共分5次注射完。四組分別于術(shù)后1h、3d、7d、10d將腫瘤兔處死，每次6只。其中第3d、7d、10d處死前行CT增強掃描，觀察腫瘤邊緣的影像學特征及處死后的大體標本、病理切片，評價腫瘤的壞死情況。 結(jié)果 A組：術(shù)中CT增強可見明顯環(huán)形強化。術(shù)后（1）1h：CT平掃可見低密度圓形或橢圓形腫塊影；大體標本可見腫瘤邊緣呈魚肉狀，腫瘤中心液化壞死；病理低倍鏡下組織內(nèi)多灶浸潤性癌巢，高倍鏡下癌細胞呈條索狀或腺樣排列，異型明顯并可見核分裂象。（2）3d、7d、10d：腫瘤逐漸增大，余表現(xiàn)同前。 B組：術(shù)中可見注入高密度混合物后，僅有少量藥物局限在腫瘤邊緣，大部分藥物彌散至腫瘤中央。術(shù)后（1）1h：CT掃描可見腫瘤邊緣及中心均可見高密度造影劑；大體標本可見腫瘤中央液化壞死，淡藍色壞死物流出，腫瘤邊緣呈淡藍色改變；病理改變同對照組。（2）3d、7d、10d：腫瘤逐漸增大，第3天CT平掃可見腫瘤中央少量高密度影，第7、10天高密度影完全消失，增強掃描均顯示腫瘤呈環(huán)形強化；病理切片顯示肌纖維細胞與腫瘤細胞臨界處僅可見少量的腫瘤細胞核碎裂及核溶解。余大體標本及病理改變同術(shù)后1h。 C組：術(shù)中可見低密度冰球形成。術(shù)后1h、3d、7d、10d：CT平掃可見腫瘤呈低密度影，，增強后顯示腫瘤上邊緣未見強化，環(huán)形強化出現(xiàn)缺口；大體標本可見血性壞死物流出，腫瘤上邊緣可見深紅色的凍傷組織，余表現(xiàn)同對照組；病理組織切片顯示，肌纖維細胞受到破壞，但仍有大量的腫瘤細胞。 D組：術(shù)中可見低密度冰球邊緣有弧形高密度影。術(shù)后（1）1h：腫瘤上邊緣可見深紅色的凍傷組織，余大體標本及病理同B組表現(xiàn)。（2）3d、7d、10d：CT增強掃描顯示腫瘤上邊緣同C組，下邊緣環(huán)形強化出現(xiàn)缺口并逐漸增大。大體標本可見腫瘤邊緣呈不連續(xù)的魚肉狀改變，上缺口處呈凍傷表現(xiàn)，下缺口處呈壞死表現(xiàn)。病理切片顯示，壞死側(cè)可見大量腫瘤細胞輪廓消失，核碎裂及核溶解，細胞漿崩解，呈均質(zhì)狀；腫瘤存活側(cè)可見大量腫瘤細胞浸潤。結(jié)論 （1）兔背部VX2腫瘤模型采用經(jīng)皮穿刺活檢法種植腫瘤，方法簡單，成功率高，腫瘤形狀較規(guī)則，具有較好的實驗重復性。（2）化學冷凍消融對混合的藥物具有適形分布的作用，可延長藥物與病變邊緣腫瘤細胞的作用時間，較單純化學消融及冷凍消融滅活邊緣腫瘤細胞具有明顯的優(yōu)勢。
[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.

【學位授予單位】：中國人民解放軍醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R73-36

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