微波消融对囊性病变及囊实性肿瘤热毁损作用及热场分布的实验研究

发布时间：2017-12-31 07:20

本文关键词：微波消融对囊性病变及囊实性肿瘤热毁损作用及热场分布的实验研究　出处：《北京协和医学院》2017年博士论文　论文类型：学位论文

【摘要】：目的通过模拟原位膀胱癌生长规律建立兔膀胱VX2移植瘤动物模型,探讨研究其生物学特性及影像学表现。方法新西兰大白兔共25只,均应用同轴法穿刺置入VX2细胞株接种于兔膀胱,分别于接种术后第2～4周行CT影像学评估肿瘤种植及生长情况,取兔膀胱组织标本行大体解剖及病理学检查,同时观察腹腔淋巴结及肝肺转移情况。结果22只实验兔建模成功,植瘤成功率为88.0%(22/25),第 2、3、4 周瘤体平均长径分别为 1.38±0.20cm、2.30±0.08cm、3.22±0.24cm,且肿瘤体积变化有显著差异(P0.01)。VX2移植瘤CT表现为膀胱壁局部不规则增厚或肿块突起,呈均匀强化(2周)或环型强化(3、4周),膀胱腔内呈不同程度充盈缺损。肿瘤组织标本形态及其影像学特征基本相符,病理学表现为血管丰富的低分化鳞状细胞癌,呈浸润性生长,3周后瘤体中心出现坏死,3～4周出现肝、肺及腹腔淋巴结转移。结论成功建立了兔膀胱VX2移植瘤模型,基本反应了膀胱癌的发生与发展过程,并适合CT动态观察及实验研究。目的应用兔膀胱及VX2移植瘤膀胱癌模拟囊性病变及囊实性肿瘤,研究设计并构建囊性病变及囊实性肿瘤实验模型。方法制备离体兔正常膀胱及VX2移植瘤膀胱,通过琼脂糖凝胶固定包埋建立囊性病变及囊实性肿瘤模型,以囊性、囊实性及兔膀胱最大横径分标准分为4组,组Ⅰ囊性病变模型(3.0cm)、组Ⅱ囊实性肿瘤模型(3.0cm)、组Ⅲ囊性病变模型(5.0cm)、组Ⅳ囊实性肿瘤模型(5.0cm),平均每组各12只实验兔,制成后分别行CT影像学评估,统计学分析。结果本实验共采用48只实验兔,其中包括24只正常实验兔及24只VX2移植瘤膀胱实验兔,均顺利麻醉成功,共完成48次腹壁切开、输尿管与膀胱颈部结扎及分离操作,平均时间约为22.0±2.7min,顺利完整取出45例(93.75%),其中兔正常膀胱22例(45.83%),VX2移植瘤膀胱23例(47.92%),3例(6.25%)由于操作过程中分离损伤膀胱壁及VX2肿瘤腹壁转移,无法完整取出兔膀胱。本次实验选择浓度为4g/200ml的琼脂糖作为凝胶剂进行可视化固定基的制备,琼脂糖溶液温度在45°C～40° C内作为离体膀胱及VX2移植瘤膀胱置入的理想温度窗,平均每例琼脂糖凝胶包埋固定膀胱时间为45.0±5.2min,凝胶固定基强度及透光度适于模型制作。囊性病变模型CT扫描所示呈等密度影,膀胱壁呈条带状稍高密度影;囊腔内注入对比剂后CT扫描所示囊腔形态规整,边界清晰,其内可见高密度液体影。囊实性肿瘤模型CT扫描所示呈等密度影,膀胱壁及VX2移植瘤呈稍高密度影;囊腔内注入对比剂后CT扫描所示囊腔内可见VX2移植瘤的充盈缺损影,瘤体平均长径为1.65±0.51cm。结论成功建立了囊性病变及囊实性肿瘤实验模型,该模型理化性质稳定,制备过程安全、简单,重复性好,并适合CT影像学评估及实验研究。目的研究微波消融对囊性病变及囊实性肿瘤热毁损作用的有效性及可行性,并探讨其消融功率、时间参数的对应关系及温度变化规律。方法63例正常实验兔及63例VX2移植瘤膀胱兔均行静脉麻醉,常规消毒铺巾切开,取得离体正常兔膀胱及VX2移植瘤膀胱,经琼脂糖凝胶固定包埋后建立成囊性病变及囊实性肿瘤实验模型。根据囊性、囊实性、兔膀胱最大横径及消融情况作为分组标准分为:组Ⅰ、组Ⅵ为无消融对照组,组Ⅱ、组Ⅲ、组Ⅵ、组Ⅴ分别进行瓦控模式(固定功率60W)消融及温控模式(测温点维持70° C)消融实验,每组消融分别持续4min、6min、8min、10min、12min。消融结束后,均分别从琼脂糖凝胶内取出膀胱及VX2移植瘤膀胱行大体解剖及病理学检查,统计学分析。结果完成建立囊性病变模型62例,建立囊实性肿瘤模型62例,2例因膀胱壁损伤漏液及VX2肿瘤腹壁转移导致建模失败。组Ⅰ、组Ⅵ作为消融对照组,未进行消融,镜下可见正常膀胱腔内壁上皮细胞形态及胞内结构完整,固有层、肌层细胞形态、结构完整。组Ⅱ、Ⅲ、Ⅳ、Ⅴ作为囊性病变及囊实性肿瘤消融实验组,消融功率及囊壁温度呈正相关,囊壁均达到有效消融温度(70° C),光镜下显示膀胱壁粘膜上皮细胞变性坏死,膀胱壁正常组织结构消失,VX2肿瘤细胞表现为凝固性坏死,核固缩,核碎裂。结论兔正常膀胱及VX2移植瘤膀胱模拟建立的囊性病变及囊实性肿瘤适于热消融实验研究,证明了微波消融热毁损作用对囊性病变及囊实性肿瘤是有效、可行的。目的研究微波热场在均一液性介质中的分布形态及均匀性,探讨微波热能在液性介质中传递的方式。方法通过应用64例正常新西兰兔膀胱模拟在体/离体囊性病变模型,根据囊性模型最大横径(3cm、5cm)及在体/离体状态作为分组标准分为消融实验组及对照组,消融实验组均设定固定功率(40W、60W、80W),消融过程中对囊性模型左侧壁、右侧壁、顶壁、底部及囊腔内液体进行实时测温,同时利用红外热像仪对囊性模型局部及整体的热场形态、分布进行实时动态监测,消融结束后行大体解剖及病理学检查,统计学分析。结果本实验应用微波针对在体/离体囊性模型共完成60例热消融实验,对照组4例未进行消融实验。平均每例热消融实验对5个位点完成25次/例温度测量。在体/离体囊性模型在固定横径条件下,囊壁及囊液温度变化速率与微波功率成呈正相关性。消融过程中相同水平位置的左、右侧囊壁温度相近(P0.05),其平均温度低于囊顶部及囊腔内囊液测量温度(P0.05),且均明显高于囊底部温度(P0.01),各测温点温度值均趋于平衡。在体/离体囊性模型内热场呈区域性分布,高温热场区域范围与消融时间呈相关性,热场均匀且完整覆盖整个囊性模型,囊壁及囊液内各测温点温度值均达有效消融温度(70° C)。光镜下可见对照组显示正常膀胱腔内壁上皮细胞形态及胞内结构完整,固有层、肌层细胞形态、结构完整;消融实验组显示膀胱壁粘膜上皮细胞变性坏死,内壁上皮细胞完全脱落,固有层、肌层正常组织结构消失。结论微波热能在液性介质中通过热对流的方式传导,在均一液性介质内微波热场分布形态具有区域性及均匀性,可适于囊性病变消融治疗。
[Abstract]:Objective to establish the growth law of rabbit bladder VX2 transplanted tumor animal model by simulating orthotopic bladder cancer, study its biological characteristics and imaging methods. A total of 25 New Zealand white rabbits, both the application of coaxial method puncture in VX2 cells inoculated in rabbit bladder, inoculated with after second to 4 weeks for CT imaging evaluation of tumor planting and growth of rabbit bladder tissue specimens of gross anatomy and pathological examination, abdominal lymph node and liver metastasis were observed. Results 22 rabbits were transplanted successfully modeled, the success rate was 88% (22/25), the average diameter of the tumor 2,3,4 weeks were 1.38 + 0.20cm, 2.30 + 0.08cm 3.22, + 0.24cm, and the changes of tumor volume were significantly different (P0.01).VX2 tumor CT showed partial bladder wall thickening or lump irregular protrusions, homogenous enhancement (2 weeks) or circular enhancement (3,4 weeks), the bladder cavity showed different degrees of charge Ying defect. Tumor tissue morphology and imaging features consistent with the pathological manifestations of poorly differentiated squamous cell carcinoma vascularity, infiltrative growth, 3 weeks after the center of tumor necrosis, 3 ~ 4 weeks of liver, lung and abdominal lymph node metastasis. Conclusion the establishment of rabbit VX2 transplanted tumor of bladder the basic reaction model, the occurrence and development of bladder cancer, and is suitable for observation and Experimental Research on dynamic CT. Application of rabbit bladder and bladder cancer VX2 xenografts in simulated cystic lesions and cystic tumor research, design and construction of cystic lesions and cystic tumor experimental models. Preparation method of isolated rabbit normal the bladder and VX2 transplanted tumor of bladder by agarose gel immobilized in a cystic lesion and cystic tumor model with cystic, cystic and rabbit bladder maximum diameter standard is divided into 4 groups, group I cystic lesion model (3.0cm), group II cystic Tumor model (3.0cm), group III cystic lesion model (5.0cm), group IV cystic tumor model (5.0cm), an average of each of the 12 rabbits were made, respectively after CT imaging assessment and statistical analysis. The results of this experiment using a total of 48 rabbits, including 24 normal rabbits and 24 VX2 of transplanted tumor of bladder in rabbits, were successfully anesthetized successfully, completed a total of 48 abdominal wall incision, ureter and bladder neck ligation and separation operation, the average time is about 22 + 2.7min, successfully complete removal of 45 cases (93.75%), including 22 cases of normal rabbit bladder (45.83%), VX2 transplanted tumor of bladder 23 (47.92% cases), 3 cases (6.25%) due to injury of bladder wall and separation of VX2 tumor of abdominal wall metastasis during operation, unable to complete removal of rabbit bladder. This experiment was selected for 4g/200ml agarose was visualized as gel fixed base preparation, agarose solution at a temperature of 45 DEG C to 40 DEG C in For the ideal temperature window of isolated bladder and bladder VX2 tumor implantation, with an average of agarose gel entrapped bladder time was 45 + 5.2min, gel strength and transmittance of the fixed base for model making. Cystic lesions in model CT scan shown in density, the bladder wall was banded slightly high density; intracavitary injection of contrast CT scan showed cysts with regular shape, clear boundary, which showed high density liquid film. Cystic tumor model was shown in CT scan density, bladder wall and VX2 tumor showed slightly high density; intracavitary injection of contrast CT scan shows cystic cavity visible VX2 tumor filling defect, tumor mean diameter was 1.65 + 0.51cm. has been successfully established cystic lesions and cystic tumor experimental model, the model is stable in physical and chemical properties, the preparation process is simple, safe, reproducible, and suitable for CT imaging and real Experimental study on microwave ablation. Objective to study the damage effect on cystic lesions and cystic tumor thermal effectiveness and feasibility, and to explore the relationship between ablation power, temperature and time variation parameters. Methods 63 normal rabbits and 63 cases of VX2 tumor rabbit urinary bladder were treated with intravenous anesthesia, the conventional disinfection shop towel made incision, isolated bladder and normal rabbit VX2 transplanted tumor of bladder by agarose gel immobilized after establishing cystic lesions and cystic tumor. According to the experimental model of cystic, cystic and solid, as the grouping criteria are divided into maximum diameter and ablation of rabbit bladder: group I, group VI for free ablation group, group II, group III, VI group, group V were wakong mode (fixed power 60W) ablation and temperature control mode (temperature maintaining 70 DEG C) ablation, ablation group respectively for 4min, 6min, 8min, 10min, 12min. after ablation, respectively from the agarose gel VX2 transplanted tumor of bladder and bladder examination, learn anatomy and pathological statistical analysis. Results the complete set out of gum cystic lesion model in 62 cases, the establishment of cystic tumor model in 62 cases, 2 cases of bladder wall damage and leakage of VX2 tumor metastasis to the abdominal wall modeling failure. The group I and group VI as ablation the control group, without ablation, microscopically normal bladder cavity epithelial cells and intracellular structural integrity, lamina propria, muscle cell morphology, structural integrity. In group II, III, IV, V as cystic lesions and cystic tumor ablation group, ablation power and the wall temperature were positively correlated the cyst wall, reached effective ablation temperature (70 degrees C), light microscope showed that the bladder mucosa epithelial cell degeneration and necrosis, disappearance of normal bladder wall tissue structure, VX2 tumor cells showed coagulation necrosis, nuclear condensation, nuclear fragmentation. Conclusion the rabbit normal bladder and bladder tumor model VX2 Quasi cystic lesions and cystic tumor is suitable for thermal ablation experiments proved that microwave ablation ablation is effective and feasible for cystic lesions and cystic tumors. The distribution in homogeneous liquid medium and the homogeneity of the study on microwave thermal field of microwave heat transfer in liquid medium. Methods by using 64 normal New Zealand rabbit bladder simulation in vitro and in vivo model of cystic lesions, according to the cystic model of maximum diameter (3cm, 5cm) and in vitro and in vivo as grouping criteria are divided into experimental ablation group and control group, experimental group were fixed ablation (power 40W, 60W, 80W), the ablation process of the cystic wall model of left, right side wall, a top wall, bottom and intracavitary liquid for real-time measurement of the cystic, and model of thermal field form the local and overall distribution of the infrared thermal imager, real-time dynamic monitoring, node ablation Check, after gross anatomy and pathological study of beam statistical analysis. The results of this experiment for the application of microwave ablation experiments in vitro and in vivo model of cystic completed a total of 60 cases, 4 cases in the control group without ablation experiment. Average thermal ablation experiments on 5 sites completed 25 cases / in vivo / temperature measurement. Isolated cystic diameter model in fixed condition, cystic wall and cyst fluid temperature change rate and the microwave power into the same horizontal position. There was a positive correlation between the ablation process of the left and right wall temperature (P0.05), close to the average temperature is lower than the top bag and cyst of internal capsule liquid temperature (P0.05), and sac were significantly higher than that of the bottom temperature (P0.01), the temperature values are balanced. In vitro and in vivo model of cystic thermal field were regional distribution, thermal field area and ablation time correlated, thermal field uniform and complete coverage of the entire model of cystic, cystic wall and cyst fluid The temperature value reached effective ablation temperature (70 degrees C). Under light microscope, the control group showed normal bladder cavity epithelial cells and intracellular structural integrity, lamina propria, muscle cell morphology, structural integrity; the experimental group showed ablation of bladder wall epithelial cell degeneration and necrosis, epithelial lining cells completely shedding, lamina propria, muscular layer of normal tissue structure disappeared. Conclusion microwave energy in liquid medium by conduction convection, in homogeneous liquid medium microwave thermal distribution has regional and uniformity, is suitable for cystic lesion ablation.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R730.5

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