超声引导经皮微波消融治疗子宫腺肌病对生育功能影响的初步实验与临床研究

发布时间：2018-03-11 01:28

本文选题：超声检查/介入性　切入点：微波消融　出处：《中国人民解放军医学院》2016年博士论文　论文类型：学位论文

【摘要】：目的：1、探讨自体内膜种植法建立Wistar大鼠子宫腺肌病模型的可行性和建模成功率;2、探讨自体内膜种植法建立猕猴子宫腺肌病动物模型的可行性和建模成功率并加以评价,建模成功后探讨超声引导下经皮微波消融(Ultrasound-guided Percutaneous Microwave Ablation, UPMWA)治疗猕猴子宫腺肌病动物模型的可行性及安全性；3、通过随访UPMWA治疗子宫肌层良性病变患者术后无计划妊娠情况,探讨UPMWA治疗对患者自然妊娠的影响。资料和方法：第一部分子宫腺肌病动物模型建立的实验研究：1、28只成熟未孕雌性Wistar大鼠随机分为建模组18只和对照组10只,建模组开腹截取一侧(左)子宫,刮取内膜种植到另一侧(右)子宫肌层内;对照组同法开腹手术,不进行内膜种植而是注射等量生理盐水。术前及术后1、2个月子宫大体标本测量子宫体厚度,镜下观察肌层组织内膜腺体浸润情况,判断术后1、2个月建模效果。2、健康成熟雌性猕猴6只(其中5只为实验组,1只为空白对照组),建模手术组经开腹手术取子宫内膜,种植到子宫前壁肌层内,术后第9个月行超声引导下穿刺活检行组织病理学检查,判断建模效果,并于术前及术后第1、3、6、9、12个月超声观察及监测血清CA125、CA19-9及血清泌乳素(Prolactin,PRL)水平,术前及术后9个月行盆腔核磁共振(Magnetic Resonance Imaging, MRI)检查。对照组猕猴不行建模手术,同期进行相关检查。第二部分猕猴子宫腺肌病动物模型超声引导经皮微波消融治疗的实验研究：第一部分研究中子宫腺肌病建模成功猕猴3只,于建模手术后的第12个月行UPMWA治疗。微波输出功率为20W,作用时间80-100s,治疗前及治疗后行经静脉超声造影(Contrast-enhanced Ultrasound, CEUS)检查评价消融范围及消融率。第三部分超声引导经皮微波消融治疗子宫肌层良性病变后妊娠情况的随访研究：随访并记录2007年6月～2015年9月在本院行UPMWA治疗的子宫肌瘤和子宫腺肌病患者治疗后自然妊娠情况、妊娠预后、妊娠结局及相关产科并发症。结果：第一部分：1、建模组18只大鼠术后1、2个月均建模成功,成功率100%(18/18)。术后1、2个月建模组手术切除子宫大体标本测量的子宫体厚度较术前增加,术后2个月测值较术后1个月增加,差异有统计学意义(P0.05)：对照组子宫大体标本测值无明显变化。HE染色镜下观察建模组子宫肌层内可见子宫内膜腺体样结构,且随建模时间的增加其范围有增大趋势;对照组子宫肌层内未见子宫内膜腺体结构。2、手术建模组5只猕猴中4只术后一般情况良好,1只术后6个半月时因自食猴毛导致上消化道梗阻死亡;3只猕猴组织穿刺活检、死亡猕猴大体标本经病理学检查镜下子宫肌层内见子宫内膜腺体,建模成功率80%(4/5)。1只建模组猕猴和对照组猕猴子宫前壁组织活检镜下子宫肌层内未见子宫内膜腺体结构。猕猴月经周期、阴道涂片变化规律及子宫影像学表现与人类相似,建模成功组猕猴子宫影像学表现亦与人子宫腺肌病影像学表现相似。建模成功组猕猴术后血清CA125及PRL水平有升高趋势。第二部分：3只猕猴子宫腺肌病动物模型均顺利进行了UPMWA治疗,过程顺利,术中猕猴无明显不适反应,术后无严重并发症,通过CEUS评价消融范围分别为6.8x4.9x5.1mm、 8.2x4.8x5.4mm,8.0x5.4x5.2mm,消融率分别为91.6%、95.3%和100%。第三部分：UPMWA治疗后共19例患者自然受孕22次,21次宫内孕,1次宫颈妊娠。其中子宫肌瘤患者11例,自然受孕12次;子宫腺肌病患者8例,自然受孕10次。自然妊娠的时间为治疗后的5-30个月,平均(14.5±6-3)个月。消融前已生育无再生育要求者13例,自然受孕16例次,其中1例次为宫颈妊娠(人工终止妊娠),1例次于孕48天时胚胎停止发育,1例次于孕56天时自然流产,其余患者均选择人工或药物流产。选择持续妊娠者6例,5例均剖宫产产下健康婴儿(其中2例治疗前曾被诊断为不孕),1倒随访至孕26周失访;5例生产者均无子宫破裂、无产后出血等严重产科并发症。结论：1、自体内膜种植法建立大鼠子宫腺肌病模型可行,具有建模诱导时间短,成功率高的优势。2、自体内膜种植法建立猕猴子宫腺肌病模型可行,是一种有效的、建模成功率较高的建模方法,不同猕猴的个体差异是建模成功与否的关键因素。猕猴子宫腺肌病动物模型的MRI及超声影像学表现与人子宫腺肌病影像学表现相似。建模手术后,猕猴血清CA125及PRL水平有升高趋势,与内膜异位的发生发展相关,与临床研究结果一致,CA125和PRL可作为评价建模情况及治疗后疗效评价的指标。3、UPMWA治疗猕猴子宫腺肌病动物模型是一种安全有效的治疗方法,术后不良反应少,无严重并发症发生,为探讨UPMWA治疗对生育影响奠定实验基础;但由于猕猴子宫体体积相对较小,该方法对术者手术技巧要求较高,需通过实时超声观察避免损伤周围正常组织。4、UPMWA治疗子宫肌瘤和子宫腺肌病对患者自然受孕能力无明显影响,对持续妊娠及妊娠预后的影响应进一步行前瞻性大样本研究。
[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.

【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R711.71;R445.1

【相似文献】