本文關鍵詞：微波消融對囊性病變及囊實性腫瘤熱毀損作用及熱場分布的實驗研究　出處：《北京協(xié)和醫(yī)學院》2017年博士論文　論文類型：學位論文

  更多相關文章： 膀胱腫瘤 動物模型 VX2 CT VX2腫瘤 囊性病變 囊實性腫瘤 動物實驗 微波消融 囊性病變 囊實性腫瘤 VX2 動物實驗 微波/治療應用 溫度場 液性介質 囊性病變

【摘要】：目的通過模擬原位膀胱癌生長規(guī)律建立兔膀胱VX2移植瘤動物模型,探討研究其生物學特性及影像學表現(xiàn)。方法新西蘭大白兔共25只,均應用同軸法穿刺置入VX2細胞株接種于兔膀胱,分別于接種術后第2～4周行CT影像學評估腫瘤種植及生長情況,取兔膀胱組織標本行大體解剖及病理學檢查,同時觀察腹腔淋巴結及肝肺轉移情況。結果22只實驗兔建模成功,植瘤成功率為88.0%(22/25),第 2、3、4 周瘤體平均長徑分別為 1.38±0.20cm、2.30±0.08cm、3.22±0.24cm,且腫瘤體積變化有顯著差異(P0.01)。VX2移植瘤CT表現(xiàn)為膀胱壁局部不規(guī)則增厚或腫塊突起,呈均勻強化(2周)或環(huán)型強化(3、4周),膀胱腔內(nèi)呈不同程度充盈缺損。腫瘤組織標本形態(tài)及其影像學特征基本相符,病理學表現(xiàn)為血管豐富的低分化鱗狀細胞癌,呈浸潤性生長,3周后瘤體中心出現(xiàn)壞死,3～4周出現(xiàn)肝、肺及腹腔淋巴結轉移。結論成功建立了兔膀胱VX2移植瘤模型,基本反應了膀胱癌的發(fā)生與發(fā)展過程,并適合CT動態(tài)觀察及實驗研究。目的應用兔膀胱及VX2移植瘤膀胱癌模擬囊性病變及囊實性腫瘤,研究設計并構建囊性病變及囊實性腫瘤實驗模型。方法制備離體兔正常膀胱及VX2移植瘤膀胱,通過瓊脂糖凝膠固定包埋建立囊性病變及囊實性腫瘤模型,以囊性、囊實性及兔膀胱最大橫徑分標準分為4組,組Ⅰ囊性病變模型(3.0cm)、組Ⅱ囊實性腫瘤模型(3.0cm)、組Ⅲ囊性病變模型(5.0cm)、組Ⅳ囊實性腫瘤模型(5.0cm),平均每組各12只實驗兔,制成后分別行CT影像學評估,統(tǒng)計學分析。結果本實驗共采用48只實驗兔,其中包括24只正常實驗兔及24只VX2移植瘤膀胱實驗兔,均順利麻醉成功,共完成48次腹壁切開、輸尿管與膀胱頸部結扎及分離操作,平均時間約為22.0±2.7min,順利完整取出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%)由于操作過程中分離損傷膀胱壁及VX2腫瘤腹壁轉移,無法完整取出兔膀胱。本次實驗選擇濃度為4g/200ml的瓊脂糖作為凝膠劑進行可視化固定基的制備,瓊脂糖溶液溫度在45°C～40° C內(nèi)作為離體膀胱及VX2移植瘤膀胱置入的理想溫度窗,平均每例瓊脂糖凝膠包埋固定膀胱時間為45.0±5.2min,凝膠固定基強度及透光度適于模型制作。囊性病變模型CT掃描所示呈等密度影,膀胱壁呈條帶狀稍高密度影;囊腔內(nèi)注入對比劑后CT掃描所示囊腔形態(tài)規(guī)整,邊界清晰,其內(nèi)可見高密度液體影。囊實性腫瘤模型CT掃描所示呈等密度影,膀胱壁及VX2移植瘤呈稍高密度影;囊腔內(nèi)注入對比劑后CT掃描所示囊腔內(nèi)可見VX2移植瘤的充盈缺損影,瘤體平均長徑為1.65±0.51cm。結論成功建立了囊性病變及囊實性腫瘤實驗模型,該模型理化性質穩(wěn)定,制備過程安全、簡單,重復性好,并適合CT影像學評估及實驗研究。目的研究微波消融對囊性病變及囊實性腫瘤熱毀損作用的有效性及可行性,并探討其消融功率、時間參數(shù)的對應關系及溫度變化規(guī)律。方法63例正常實驗兔及63例VX2移植瘤膀胱兔均行靜脈麻醉,常規(guī)消毒鋪巾切開,取得離體正常兔膀胱及VX2移植瘤膀胱,經(jīng)瓊脂糖凝膠固定包埋后建立成囊性病變及囊實性腫瘤實驗模型。根據(jù)囊性、囊實性、兔膀胱最大橫徑及消融情況作為分組標準分為:組Ⅰ、組Ⅵ為無消融對照組,組Ⅱ、組Ⅲ、組Ⅵ、組Ⅴ分別進行瓦控模式(固定功率60W)消融及溫控模式(測溫點維持70° C)消融實驗,每組消融分別持續(xù)4min、6min、8min、10min、12min。消融結束后,均分別從瓊脂糖凝膠內(nèi)取出膀胱及VX2移植瘤膀胱行大體解剖及病理學檢查,統(tǒng)計學分析。結果完成建立囊性病變模型62例,建立囊實性腫瘤模型62例,2例因膀胱壁損傷漏液及VX2腫瘤腹壁轉移導致建模失敗。組Ⅰ、組Ⅵ作為消融對照組,未進行消融,鏡下可見正常膀胱腔內(nèi)壁上皮細胞形態(tài)及胞內(nèi)結構完整,固有層、肌層細胞形態(tài)、結構完整。組Ⅱ、Ⅲ、Ⅳ、Ⅴ作為囊性病變及囊實性腫瘤消融實驗組,消融功率及囊壁溫度呈正相關,囊壁均達到有效消融溫度(70° C),光鏡下顯示膀胱壁粘膜上皮細胞變性壞死,膀胱壁正常組織結構消失,VX2腫瘤細胞表現(xiàn)為凝固性壞死,核固縮,核碎裂。結論兔正常膀胱及VX2移植瘤膀胱模擬建立的囊性病變及囊實性腫瘤適于熱消融實驗研究,證明了微波消融熱毀損作用對囊性病變及囊實性腫瘤是有效、可行的。目的研究微波熱場在均一液性介質中的分布形態(tài)及均勻性,探討微波熱能在液性介質中傳遞的方式。方法通過應用64例正常新西蘭兔膀胱模擬在體/離體囊性病變模型,根據(jù)囊性模型最大橫徑(3cm、5cm)及在體/離體狀態(tài)作為分組標準分為消融實驗組及對照組,消融實驗組均設定固定功率(40W、60W、80W),消融過程中對囊性模型左側壁、右側壁、頂壁、底部及囊腔內(nèi)液體進行實時測溫,同時利用紅外熱像儀對囊性模型局部及整體的熱場形態(tài)、分布進行實時動態(tài)監(jiān)測,消融結束后行大體解剖及病理學檢查,統(tǒng)計學分析。結果本實驗應用微波針對在體/離體囊性模型共完成60例熱消融實驗,對照組4例未進行消融實驗。平均每例熱消融實驗對5個位點完成25次/例溫度測量。在體/離體囊性模型在固定橫徑條件下,囊壁及囊液溫度變化速率與微波功率成呈正相關性。消融過程中相同水平位置的左、右側囊壁溫度相近(P0.05),其平均溫度低于囊頂部及囊腔內(nèi)囊液測量溫度(P0.05),且均明顯高于囊底部溫度(P0.01),各測溫點溫度值均趨于平衡。在體/離體囊性模型內(nèi)熱場呈區(qū)域性分布,高溫熱場區(qū)域范圍與消融時間呈相關性,熱場均勻且完整覆蓋整個囊性模型,囊壁及囊液內(nèi)各測溫點溫度值均達有效消融溫度(70° C)。光鏡下可見對照組顯示正常膀胱腔內(nèi)壁上皮細胞形態(tài)及胞內(nèi)結構完整,固有層、肌層細胞形態(tài)、結構完整;消融實驗組顯示膀胱壁粘膜上皮細胞變性壞死,內(nèi)壁上皮細胞完全脫落,固有層、肌層正常組織結構消失。結論微波熱能在液性介質中通過熱對流的方式傳導,在均一液性介質內(nèi)微波熱場分布形態(tài)具有區(qū)域性及均勻性,可適于囊性病變消融治療。
[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.

【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R730.5

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