微波消融对甲状腺良性结节的疗效及影响因素的临床研究

发布时间：2017-12-28 09:14

本文关键词：微波消融对甲状腺良性结节的疗效及影响因素的临床研究　出处：《第三军医大学》2017年博士论文　论文类型：学位论文

【摘要】：背景及目的甲状腺结节(Thyroid nodules)为临床多发常见疾病,流行病学调查显示,采用常规触诊甲状腺结节检出率为3-7%,随着影像检查技术的发展,高频超声则将检出率提高至20-76%。近年研究发现代谢综合征是甲状腺结节的危险因素。目前多数学者将甲状腺结节分为囊性、实性和囊实性、单一和多发、良性和恶性,甲状腺结节以良性多见,恶性约占5%,目前针对恶性结节以手术治疗为主,而对于良性结节,临床多数患者仍有积极治疗的要求,传统治疗方法为超声引导下经皮穿刺间质内注射无水乙醇消融,常存在乙醇弥散不均、硬化程度不一致的缺陷,此外,乙醇的流向受控性较差,容易向结节周围渗漏导致化学性粘连。手术治疗甲状腺良性结节适应症较窄,仅用于胸骨后或纵膈内结节并伴随压迫症状,常有术后出血、感染、喉返神经损伤、甲状旁腺损害及甲状腺功能减退等并发症,常不被患者接受。药物治疗为TSH抑制疗法,然而部分研究者则认为左旋甲状腺素不能明显抑制甲状腺结节,故其有效性存在争议。放射性碘主要用于治疗具有自主摄取功能伴甲状腺功能亢进的良性结节,治疗后仍有甲状腺功能减退的风险。所以,为甲状腺良性结节治疗寻找一种新方法亟待解决。热消融(thermal ablation)作为一种新开展的微创技术,多适用于肺、肝、肾、胰腺、乳腺、子宫等实质性器官肿瘤的治疗,近年来,国内外研究者开始尝试将超声引导下的热消融技术应用于甲状腺肿瘤治疗。热消融主要包括射频消融(radiofrequency ablation,RFA)、激光消融(laser ablation,LAT)和微波消融(microwave ablation,MWA)。其共同基本原理是利用热能使病灶细胞发生热变性和凝固性坏死,坏死组织逐渐被机体吸收,从而达到破坏病灶的目的。研究证实,射频消融治疗甲状腺肿瘤易受电流干扰、血流灌注等影响,激光消融则存在破坏范围较小等缺陷使其在临床应用中存在一定的局限性。微波消融是在超声介导下将微波能量转化成热能,从而破坏病灶组织,多用于肝肾肿瘤、子宫肌瘤等治疗,近年虽有临床研究显示其消融面积大、不易受血流灌注的影响等优点,但关于微波消融治疗甲状腺结节的相关研究较少,故微波消融成为甲状腺良性结节的一种新治疗方法值得探索。本研究通过超声引导下细针穿刺抽吸活检(fine-needle aspiration biopsy,FNAB)筛选出良性甲状腺结节,拟采用微波消融治疗甲状腺结节,细化观察术后结节体积、甲状腺相关指标的变化和并发症的发生情况,评估其疗效,进一步分析微波消融对不同性质大小结节的疗效差异性,探讨代谢及甲状腺相关指标是否成为影响疗效的因素。旨在明确微波消融治疗甲状腺良性结节的疗效性、安全性及特异性,为该治疗方案提供更多有效的临床证据,以期达到良好的治疗前景。研究方法对(2016年4月至2016年8月)第三军医大学附属新桥医院内分泌科收治住院的45例(63枚)经细针穿刺抽吸活检筛查诊断的甲状腺良性结节患者(TI-RADS分类1-3类,Bethesda分类Ⅱ类),微波消融后随访3月进行分析。做出下列评价:(1)总体疗效评价:通过比较术前后结节经线、体积及血流信号改变,甲状腺相关指标的改变及并发症来评价其疗效;(2)亚组评价:按结节内部回声的不同(在细针穿刺抽吸活检筛查出良性结节基础上分为囊性、囊实性、实性)分别比较术后结节体积、甲状腺相关指标的变化情况来探讨微波消融对不同性质、体积结节治疗的差异性;(3)影响因素评价:比较代谢及甲状腺相关指标对其疗效的影响。研究结果1.微波消融治疗甲状腺良性结节的疗效比较结果结果表明,微波消融后结节体积呈持续缩小趋势,术后1月体积明显缩小,至术后3月平均体积缩小率达到71.60%,具有显著统计学意义(P0.0001)。结节内部或边缘超声血流信号显示术后1天即明显消减(P0.001),至术后3月52.46%结节血流信号可完全消失。术前后甲状腺功能及甲状腺自身抗体比较并无统计学差异。治疗过程中所有患者均能耐受并完成治疗,出现术中疼痛(31.1%)、声音嘶哑(20%)、出血(20%),大部分症状在术后24小时内得到消减,1例患者术后3月声嘶症状完全缓解,全程均未予以特殊处理。2.微波消融治疗甲状腺良性结节的亚组间疗效比较结果术后囊实性结节、实性结节及囊性结节之间的平均体积缩小率均存在统计学意义,其中囊实性结节缩小最为显著(平均体积缩小率为63.29%);对结节体积变化进行分析,发现至随访末期不同大小的结节体积均缩小,但体积1ml的结节体积变化(体积变化率)均不显著。3.影响因素评价结果初步比较了代谢及甲状腺相关指标对微波消融治疗甲状腺良性结节的疗效影响,显示ALT、AST、TC、CREA及TSH值越高,结节体积变化(体积变化率)越小,HDL-C、FT4、TT4与体积变化(体积变化率)则呈正相关表现,而血压、血糖与之无明显相关性。研究结论综上所述,微波消融作为一类热消融技术应用于甲状腺良性结节治疗中具有明确的疗效性和安全性。微波消融均能显著缩小不同性质及体积较大的结节,对于囊实性结节,微波消融可能存在一定的优越性;而针对小体积的甲状腺结节,尤其是体积1ml的结节,微波消融范围可能超过结节,如需微创治疗可以优先选择激光消融。微波消融严重的并发症是损伤神经,如果操作合理,严格遵循治疗规范,结合超声引导下定位准确,其发生率明显下降,同时我们也需注意:对位置靠近神经的结节,能量的释放尽量避开神经处,可考虑不完全消融。血脂、肝肾功损害及TSH等因素可负面干预治疗后甲状腺良性结节的体积缩小,从而影响其疗效。研究背景作为过氧化物酶体增殖物激活受体γ(peroxisome proliferator activatedreceptor-γ,PPAR-γ)激动剂,噻唑烷二酮(thiazolidinedione,TZD)主要通过增加外周组织中的胰岛素敏感性来降低血糖,该类药物已广泛用于糖尿病的治疗。研究发现,吡格列酮除了降低血糖,还可以预防主要心血管病、酒精性脂肪性肝炎,表明其临床应用有更广泛的前景。但是,近年来的一系列大样本研究显示不一致的结果,引发了全球关于吡格列酮与膀胱癌风险的众多争议。研究目的为了寻求关于这个争议问题的原因,我们进行了分层分析,以探讨导致先前研究不一致结果的潜在混杂因素。数据来源Embase,Pub Med,Web of Science,Cochrane Central Register of Controlled Trials和Clinical Trials.gov。搜索时间为从数据库建立至2017年1月5日。研究选择包括与吡格列酮和糖尿病患者的癌症相关的所有研究(观察性研究observational study,OB和随机对照试验randomized controlled trial,RCT)。数据提取研究组成员进行了文献检索、数据提取和质量评估研究。分析目标主要分析吡格列酮和膀胱癌风险之间的关联是否因研究设计(即研究类型、调整因素、干预措施、比较剂、随访持续时间和研究人群)而不同。次要分析是评估吡格列酮和其它癌症风险之间的关系。结果来自观察性研究的2,764,731名受试者和来自随机对照试验的9,999名受试者的资料被用于鉴定吡格列酮和膀胱癌风险的分析。对于观察性研究,膀胱癌风险在全球水平的合并比值比(odds ratio,OR)为1.15(95%置信区间confidence interval,CI,1.07 1.24;P0.001)。潜在混杂因素分层分析显示,研究类型、年龄/性别、治疗持续时间、累积剂量、对照组中使用的药物、平均随访期和研究人群区域可能与结果的不一致有关。对于人群而言,欧洲人群中吡格列酮增加了膀胱癌风险(OR,1.20;95%CI,1.08-1.32;P0.001),而在美国(OR,1.03;95%CI,0.88-1.21;P=0.68)和亚洲人群(OR,1.16;95%CI,0.96-1.40;P=0.12)中没有增加膀胱癌风险。此外,在美国和亚洲地区,根据潜在混杂因素分层分析的结果也是阴性的(P0.05)。而在欧洲地区,除了未调整年龄/性别,吸烟,治疗持续时间和随访时间较短,和对照组使用罗格列酮的亚组外(P0.05),分层研究的结果也都是阳性的(P0.05)。综合观察性研究和随机对照试验,所有结果与在观察性研究中报道的结果类似。此外,吡格列酮与前列腺癌和胰腺癌的风险增加相关(P0.05),而与肝癌和脑癌的风险降低相关(P0.05)。结论和相关性吡格列酮与膀胱癌的风险需要根据不同的人群区域考虑。这一风险可能存在于欧洲,但不存在于美国和亚洲人群。在欧洲,治疗时间较长(12个月)或累积剂量的较大(28,000 mg)的患者需要更多的注意,而且吡格列酮的长期影响(≥3.6年)需要了解。并且,在将来的相关研究中应调整年龄/性别和吸烟状况,并在对照组中采用非特异性药物。此外,吡格列酮也可能涉及其它癌症。
[Abstract]:Background and objective thyroid nodule (Thyroid nodules) is a common clinical disease. Epidemiological investigation shows that the detection rate of thyroid nodules is 3-7% using conventional palpation. With the development of imaging technology, high frequency ultrasound will increase the detection rate to 20-76%. Recent studies have found that metabolic syndrome is a risk factor for thyroid nodules. At present, many scholars will be divided into cystic thyroid nodules, solid and cystic, single and multiple, benign and malignant thyroid nodules are benign, rare, malignant accounted for about 5% of the malignant nodules to surgical treatment, and for benign nodules, most patients still have positive clinical treatment requirements. The traditional treatment methods for ultrasound guided percutaneous ethanol injection interstitial ablation, often in ethanol dispersion is uneven, the degree of hardening inconsistent defects, in addition, poor flow controlled ethanol, easy to cause leakage of chemical adhesion around the nodules. Surgical treatment of benign thyroid nodules is relatively narrow. It is used only for sternal or mediastinal nodules and accompanied by compression symptoms. Postoperative complications such as postoperative bleeding, infection, recurrent laryngeal nerve injury, parathyroid gland damage and hypothyroidism are often not accepted by patients. The drug treatment is TSH inhibitory therapy, but some researchers believe that levothyroxine does not significantly inhibit thyroid nodules, so its effectiveness is controversial. Radioactive iodine is mainly used for the treatment of benign nodules with autonomic uptake and hyperthyroidism, and there is still a risk of hypothyroidism after treatment. Therefore, it is urgent to find a new method for the treatment of thyroid benign nodules. Thermal ablation (thermal ablation) as a new developed minimally invasive technique, more applicable to the lung and liver, kidney, pancreas, breast, uterus and parenchymal tumor treatment, in recent years, domestic and foreign researchers began experimenting with ultrasound guided thermal ablation technique applied in thyroid cancer treatment. Heat ablation mainly includes radiofrequency ablation (radiofrequency ablation, RFA), laser ablation (laser ablation, LAT) and microwave ablation (microwave ablation, MWA). The basic principle is to use heat energy to cause thermal denaturation and coagulating necrosis of the lesion cells, and necrotic tissue is gradually absorbed by the body, so as to achieve the purpose of destroying the lesion. It is confirmed that radiofrequency ablation is susceptible to the influence of current interference and blood perfusion, and laser ablation has some limitations, such as smaller damage scope and so on. It has some limitations in clinical application. Microwave ablation in ultrasound mediated microwave energy into heat energy, thus destroying the lesion tissue, liver and kidney for cancer, uterine fibroids and other treatment, although recent clinical studies have shown the advantages of ablation area, not easily affected by blood perfusion, but the related research on microwave ablation treatment of thyroid nodule is less, so microwave ablation is a new treatment method for benign thyroid nodules is worth exploring. Through the study of ultrasound guided fine needle aspiration biopsy (fine-needle aspiration, biopsy, FNAB) were screened for benign thyroid nodules, the microwave ablation of thyroid nodules, observe the changes and complications of refinement and thyroid nodule volume indexes related to postoperative incidence, evaluate the curative effect, further analysis of microwave ablation on different properties the size of nodules, metabolism and thyroid related indicators will become a factor affecting the efficacy. Objective to clarify the efficacy, safety and specificity of microwave ablation for benign thyroid nodules, and to provide more effective clinical evidence for this treatment plan, so as to achieve a good therapeutic prospect. Research methods (April 2016 to August 2016) admitted to the Department of Endocrinology, Xinqiao Hospital of Third Military Medical University in 45 cases (63) by fine needle aspiration biopsy in screening diagnosis of patients with benign thyroid nodules (TI-RADS classification 1-3, Bethesda classification type), microwave ablation after March were analyzed. Make the following evaluation: (1) the overall curative effect evaluation: by comparing the change of the warp, volume and blood flow signal nodules before and after operation, change and complications related indicators to evaluate the therapeutic effect of thyroid; (2) subgroup evaluation: according to the different internal echo of nodule (fine needle aspiration biopsy in screening of benign nodules based on divided into cystic, cystic and solid) changes, thyroid nodule volume related indicators were compared after microwave ablation to explore the difference of different properties, volume treatment of nodules; (3) evaluation factors: To compare the effects of thyroid metabolism and related indexes of its curative effect. Results: 1. microwave ablation treatment of benign thyroid nodules and the comparison results show that after microwave ablation nodule volume on a declining trend, after January volume was significantly reduced, and after March the average volume rate of 71.60%, there was a statistically significant (P0.0001). The internal or marginal ultrasound blood flow signals showed a significant decrease (P0.001) at 1 days after the operation, and the blood flow signal of 52.46% nodules could be completely disappeared in March after the operation. There was no statistical difference between the thyroid function and the thyroid autoantibody before and after the operation. In the course of treatment was tolerated by all patients and complete treatment, intraoperative pain (31.1%), hoarseness (20%), bleeding (20%), most of the symptoms abate in get within 24 hours after surgery, 1 cases of patients with postoperative hoarseness in March complete remission of symptoms, whole were not given special treatment. Sub groups 2. microwave ablation of benign thyroid nodules compared the average volume between postoperative cystic nodules and solid nodules and cystic nodules were found statistically significant reduced rate, the cystic nodules decreased most significantly (mean volume reduction rate was 63.29%); the nodule volume changes were analyzed. It was found at the end of follow-up, depending on the size of the nodule volume were reduced, but the nodule volume change of 1ml (volume change rate) were not significant.
【学位授予单位】：第三军医大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R581

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