本文選題：超聲檢查/介入性　切入點：微波消融　出處：《中國人民解放軍醫(yī)學院》2016年博士論文　論文類型：學位論文

【摘要】：目的：1、探討自體內膜種植法建立Wistar大鼠子宮腺肌病模型的可行性和建模成功率;2、探討自體內膜種植法建立獼猴子宮腺肌病動物模型的可行性和建模成功率并加以評價,建模成功后探討超聲引導下經皮微波消融(Ultrasound-guided Percutaneous Microwave Ablation, UPMWA)治療獼猴子宮腺肌病動物模型的可行性及安全性；3、通過隨訪UPMWA治療子宮肌層良性病變患者術后無計劃妊娠情況,探討UPMWA治療對患者自然妊娠的影響。資料和方法：第一部分子宮腺肌病動物模型建立的實驗研究：1、28只成熟未孕雌性Wistar大鼠隨機分為建模組18只和對照組10只,建模組開腹截取一側(左)子宮,刮取內膜種植到另一側(右)子宮肌層內;對照組同法開腹手術,不進行內膜種植而是注射等量生理鹽水。術前及術后1、2個月子宮大體標本測量子宮體厚度,鏡下觀察肌層組織內膜腺體浸潤情況,判斷術后1、2個月建模效果。2、健康成熟雌性獼猴6只(其中5只為實驗組,1只為空白對照組),建模手術組經開腹手術取子宮內膜,種植到子宮前壁肌層內,術后第9個月行超聲引導下穿刺活檢行組織病理學檢查,判斷建模效果,并于術前及術后第1、3、6、9、12個月超聲觀察及監(jiān)測血清CA125、CA19-9及血清泌乳素(Prolactin,PRL)水平,術前及術后9個月行盆腔核磁共振(Magnetic Resonance Imaging, MRI)檢查。對照組獼猴不行建模手術,同期進行相關檢查。第二部分獼猴子宮腺肌病動物模型超聲引導經皮微波消融治療的實驗研究：第一部分研究中子宮腺肌病建模成功獼猴3只,于建模手術后的第12個月行UPMWA治療。微波輸出功率為20W,作用時間80-100s,治療前及治療后行經靜脈超聲造影(Contrast-enhanced Ultrasound, CEUS)檢查評價消融范圍及消融率。第三部分超聲引導經皮微波消融治療子宮肌層良性病變后妊娠情況的隨訪研究：隨訪并記錄2007年6月～2015年9月在本院行UPMWA治療的子宮肌瘤和子宮腺肌病患者治療后自然妊娠情況、妊娠預后、妊娠結局及相關產科并發(fā)癥。結果：第一部分：1、建模組18只大鼠術后1、2個月均建模成功,成功率100%(18/18)。術后1、2個月建模組手術切除子宮大體標本測量的子宮體厚度較術前增加,術后2個月測值較術后1個月增加,差異有統(tǒng)計學意義(P0.05)：對照組子宮大體標本測值無明顯變化。HE染色鏡下觀察建模組子宮肌層內可見子宮內膜腺體樣結構,且隨建模時間的增加其范圍有增大趨勢;對照組子宮肌層內未見子宮內膜腺體結構。2、手術建模組5只獼猴中4只術后一般情況良好,1只術后6個半月時因自食猴毛導致上消化道梗阻死亡;3只獼猴組織穿刺活檢、死亡獼猴大體標本經病理學檢查鏡下子宮肌層內見子宮內膜腺體,建模成功率80%(4/5)。1只建模組獼猴和對照組獼猴子宮前壁組織活檢鏡下子宮肌層內未見子宮內膜腺體結構。獼猴月經周期、陰道涂片變化規(guī)律及子宮影像學表現(xiàn)與人類相似,建模成功組獼猴子宮影像學表現(xiàn)亦與人子宮腺肌病影像學表現(xiàn)相似。建模成功組獼猴術后血清CA125及PRL水平有升高趨勢。第二部分：3只獼猴子宮腺肌病動物模型均順利進行了UPMWA治療,過程順利,術中獼猴無明顯不適反應,術后無嚴重并發(fā)癥,通過CEUS評價消融范圍分別為6.8x4.9x5.1mm、 8.2x4.8x5.4mm,8.0x5.4x5.2mm,消融率分別為91.6%、95.3%和100%。第三部分：UPMWA治療后共19例患者自然受孕22次,21次宮內孕,1次宮頸妊娠。其中子宮肌瘤患者11例,自然受孕12次;子宮腺肌病患者8例,自然受孕10次。自然妊娠的時間為治療后的5-30個月,平均(14.5±6-3)個月。消融前已生育無再生育要求者13例,自然受孕16例次,其中1例次為宮頸妊娠(人工終止妊娠),1例次于孕48天時胚胎停止發(fā)育,1例次于孕56天時自然流產,其余患者均選擇人工或藥物流產。選擇持續(xù)妊娠者6例,5例均剖宮產產下健康嬰兒(其中2例治療前曾被診斷為不孕),1倒隨訪至孕26周失訪;5例生產者均無子宮破裂、無產后出血等嚴重產科并發(fā)癥。結論：1、自體內膜種植法建立大鼠子宮腺肌病模型可行,具有建模誘導時間短,成功率高的優(yōu)勢。2、自體內膜種植法建立獼猴子宮腺肌病模型可行,是一種有效的、建模成功率較高的建模方法,不同獼猴的個體差異是建模成功與否的關鍵因素。獼猴子宮腺肌病動物模型的MRI及超聲影像學表現(xiàn)與人子宮腺肌病影像學表現(xiàn)相似。建模手術后,獼猴血清CA125及PRL水平有升高趨勢,與內膜異位的發(fā)生發(fā)展相關,與臨床研究結果一致,CA125和PRL可作為評價建模情況及治療后療效評價的指標。3、UPMWA治療獼猴子宮腺肌病動物模型是一種安全有效的治療方法,術后不良反應少,無嚴重并發(fā)癥發(fā)生,為探討UPMWA治療對生育影響奠定實驗基礎;但由于獼猴子宮體體積相對較小,該方法對術者手術技巧要求較高,需通過實時超聲觀察避免損傷周圍正常組織。4、UPMWA治療子宮肌瘤和子宮腺肌病對患者自然受孕能力無明顯影響,對持續(xù)妊娠及妊娠預后的影響應進一步行前瞻性大樣本研究。
[Abstract]:Objective: 1, autologous endometrial planting method and the feasibility of modeling to establish the Wistar rat model of adenomyosis success rate; 2, autologous endometrial planting method and the feasibility of modeling macaque adenomyosis animal model and evaluate the success rate, after the success of modeling of percutaneous microwave ablation guided by ultrasound (Ultrasound-guided Percutaneous Microwave Ablation, UPMWA) is safe and effective in the treatment of adenomyosis of macaque animal model; 3, the planned pregnancy follow-up UPMWA treatment of uterine muscle benign lesions after surgery, to investigate the effect of UPMWA treatment on patients with natural pregnancy. Materials and methods: the first part experimental study on establishment of adenomyosis animal model: 1,28 mature virgin female Wistar rats were randomly divided into model group 18 rats and 10 rats in the control group, model group open interception side (left) the uterus, endometrial scraping method And to the other side (right) in the myometrium; control group with open surgery, but no endometrial planting injection of normal saline. The preoperative and postoperative 1,2 months of uterine specimens of uterus were measured to observe the thickness of muscle tissue infiltration of endometrial glands under the microscope,.2 1,2 months to judge the effect of modeling after healthy mature female 6 rhesus monkeys (5 of them as the experimental group, 1 rats as control group), operation group underwent open surgery modeling of the endometrium, planting to the anterior wall of the uterus muscle layer, after ninth months of examination for ultrasound guided biopsy for histopathology, judging the effect of modeling, and before and after surgery in 1,3,6,9,12 months of the ultrasound observation and monitoring of serum CA125, CA19-9 and serum prolactin levels (Prolactin, PRL), preoperative and postoperative 9 months for pelvic magnetic resonance (Magnetic Resonance Imaging, MRI). The control group with no monkey modeling operation. During the relevant examination. Second monkeys adenomyosis animal model experimental study on the treatment of ultrasound guided percutaneous microwave ablation: the first part of the study in adenomyosis model 3 rhesus monkeys, twelfth months UPMWA treatment model after surgery. The microwave output power is 20W, time 80-100s, were performed before and after the treatment intravenous ultrasound contrast (Contrast-enhanced Ultrasound, CEUS) evaluation of ablation range and ablation rate. The third part ultrasound follow-up study of pregnancy treatment uterine muscle benign lesions after percutaneous microwave ablation: follow-up and record from June 2007 to September 2015 in our hospital UPMWA treatment of uterine myoma and adenomyosis patients after natural pregnancy pregnancy, prognosis, outcome and related obstetric complications of pregnancy. Results: the first part: 1, model group 18 rats after 1,2 months were built into die Power, the success rate was 100% (18/18). 1,2 months after surgical removal of the uterus in model group were measured the thickness of the uterus increased compared with preoperative, postoperative 2 months 1 months compared with the measured value increased after operation, the difference was statistically significant (P0.05): control group uterine specimens measured no significant change.HE staining was observed in the myometrium visible modeling group endometrial glands like structure under microscope, and with the modeling time increased the range increases; the control group in the myometrium were endometrial gland structure.2, surgery model group 5 monkeys in the 4 postoperative general condition is good, 1 to 6 and a half months only after eating monkey hair due to upper gastrointestinal obstruction leads to death; 3 rhesus macaques biopsy specimens, death by pathological examination under the microscope in the myometrium in endometrial glands, modeling the success rate of 80% (4/5).1 group and the control group only modeling macaque rhesus monkeys before the palace wall group The fabric live in the myometrium under examination no endometrial gland structure. The macaque menstrual cycle changes, vaginal smear and uterine imaging findings similar to humans, the success of modeling group were imagingfindings are uterine adenomyosis and imaging findings of similar success group. Modeling of the rhesus monkey after operation serum CA125 and PRL levels increased the trend. The second part: 3 rhesus monkeys adenomyosis animal model were successfully carried out UPMWA treatment process smoothly, intraoperative macaque no obvious discomfort reaction, no serious postoperative complications were evaluated by CEUS ablation range were 6.8x4.9x5.1mm, 8.2x4.8x5.4mm, 8.0x5.4x5.2mm, ablation rates were 91.6%, 95.3% and third parts: UPMWA 100%. after treatment, 19 patients with natural pregnancy 22 times, 21 times and 1 times of intrauterine pregnancy, cervical pregnancy in 11 cases of uterine fibroids, natural pregnancy 12 times; 8 cases of adenomyosis patients, 1 natural conception 0. The natural pregnancy for 5-30 months after treatment, the average (14.5 + 6-3) months. Before ablation has given birth to no fertility requirements in 13 cases, 16 cases of natural conception, including 1 cases of cervical pregnancy (pregnancy termination), 1 cases in gestation day 48 embryos stop the development of 1 cases after natural abortion in pregnant 56 days, the remaining patients were selected or artificial abortion. 6 cases continued pregnancy, 5 cases of caesarean birth of a healthy baby (including 2 cases before treatment had been diagnosed), 1 were followed up to 26 weeks of pregnancy lost; 5 cases of producers there were no uterine rupture, no postpartum hemorrhage and other serious obstetric complications. Conclusion: 1. Autologous endometrial planting method to establish a rat model of adenomyosis is feasible, with modeling the induction time is short, high success rate of the advantages of.2, autologous endometrial planting method to establish the rhesus monkey model of adenomyosis is a feasible, effective, dynamic modeling higher success rate Law, individual differences in rhesus monkeys is a key factor for the success of the modeling. MRI and ultrasound images of macaque adenomyosis animal model findings and imaging features of human adenomyosis. Similar modeling after surgery, CA125 and rhesus serum levels of PRL increased, and the occurrence and development of endometrial differentiation and clinical correlation the results of the study,.3 CA125 and PRL can be used as indicators of efficacy evaluation modeling and evaluation and treatment of the UPMWA in the treatment of adenomyosis of macaque animal model is a safe and effective treatment, postoperative adverse reactions, no severe complications, in order to investigate the UPMWA treatment on the reproductive effects of experimental basis; but because the monkeys the uterine volume is relatively small, the method of high surgical technique requires patients by real-time ultrasound observation, to avoid damage to the surrounding normal tissue.4, UPMWA treatment of uterine myoma and adenomyosis in patients There is no obvious effect on the natural conception of pregnancy. The effect on the continuous pregnancy and the prognosis of pregnancy should be further studied in a prospective large sample.

【學位授予單位】：中國人民解放軍醫(yī)學院
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R711.71;R445.1

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