本文關(guān)鍵詞：微波消融對甲狀腺良性結(jié)節(jié)的療效及影響因素的臨床研究　出處：《第三軍醫(yī)大學(xué)》2017年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 甲狀腺結(jié)節(jié) 熱消融 微波消融 代謝綜合征 噻唑烷二酮 吡格列酮 膀胱癌 觀察性研究 隨機對照試驗

【摘要】：背景及目的甲狀腺結(jié)節(jié)(Thyroid nodules)為臨床多發(fā)常見疾病,流行病學(xué)調(diào)查顯示,采用常規(guī)觸診甲狀腺結(jié)節(jié)檢出率為3-7%,隨著影像檢查技術(shù)的發(fā)展,高頻超聲則將檢出率提高至20-76%。近年研究發(fā)現(xiàn)代謝綜合征是甲狀腺結(jié)節(jié)的危險因素。目前多數(shù)學(xué)者將甲狀腺結(jié)節(jié)分為囊性、實性和囊實性、單一和多發(fā)、良性和惡性,甲狀腺結(jié)節(jié)以良性多見,惡性約占5%,目前針對惡性結(jié)節(jié)以手術(shù)治療為主,而對于良性結(jié)節(jié),臨床多數(shù)患者仍有積極治療的要求,傳統(tǒng)治療方法為超聲引導(dǎo)下經(jīng)皮穿刺間質(zhì)內(nèi)注射無水乙醇消融,常存在乙醇彌散不均、硬化程度不一致的缺陷,此外,乙醇的流向受控性較差,容易向結(jié)節(jié)周圍滲漏導(dǎo)致化學(xué)性粘連。手術(shù)治療甲狀腺良性結(jié)節(jié)適應(yīng)癥較窄,僅用于胸骨后或縱膈內(nèi)結(jié)節(jié)并伴隨壓迫癥狀,常有術(shù)后出血、感染、喉返神經(jīng)損傷、甲狀旁腺損害及甲狀腺功能減退等并發(fā)癥,常不被患者接受。藥物治療為TSH抑制療法,然而部分研究者則認(rèn)為左旋甲狀腺素不能明顯抑制甲狀腺結(jié)節(jié),故其有效性存在爭議。放射性碘主要用于治療具有自主攝取功能伴甲狀腺功能亢進(jìn)的良性結(jié)節(jié),治療后仍有甲狀腺功能減退的風(fēng)險。所以,為甲狀腺良性結(jié)節(jié)治療尋找一種新方法亟待解決。熱消融(thermal ablation)作為一種新開展的微創(chuàng)技術(shù),多適用于肺、肝、腎、胰腺、乳腺、子宮等實質(zhì)性器官腫瘤的治療,近年來,國內(nèi)外研究者開始嘗試將超聲引導(dǎo)下的熱消融技術(shù)應(yīng)用于甲狀腺腫瘤治療。熱消融主要包括射頻消融(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熱能使病灶細(xì)胞發(fā)生熱變性和凝固性壞死,壞死組織逐漸被機體吸收,從而達(dá)到破壞病灶的目的。研究證實,射頻消融治療甲狀腺腫瘤易受電流干擾、血流灌注等影響,激光消融則存在破壞范圍較小等缺陷使其在臨床應(yīng)用中存在一定的局限性。微波消融是在超聲介導(dǎo)下將微波能量轉(zhuǎn)化成熱能,從而破壞病灶組織,多用于肝腎腫瘤、子宮肌瘤等治療,近年雖有臨床研究顯示其消融面積大、不易受血流灌注的影響等優(yōu)點,但關(guān)于微波消融治療甲狀腺結(jié)節(jié)的相關(guān)研究較少,故微波消融成為甲狀腺良性結(jié)節(jié)的一種新治療方法值得探索。本研究通過超聲引導(dǎo)下細(xì)針穿刺抽吸活檢(fine-needle aspiration biopsy,FNAB)篩選出良性甲狀腺結(jié)節(jié),擬采用微波消融治療甲狀腺結(jié)節(jié),細(xì)化觀察術(shù)后結(jié)節(jié)體積、甲狀腺相關(guān)指標(biāo)的變化和并發(fā)癥的發(fā)生情況,評估其療效,進(jìn)一步分析微波消融對不同性質(zhì)大小結(jié)節(jié)的療效差異性,探討代謝及甲狀腺相關(guān)指標(biāo)是否成為影響療效的因素。旨在明確微波消融治療甲狀腺良性結(jié)節(jié)的療效性、安全性及特異性,為該治療方案提供更多有效的臨床證據(jù),以期達(dá)到良好的治療前景。研究方法對(2016年4月至2016年8月)第三軍醫(yī)大學(xué)附屬新橋醫(yī)院內(nèi)分泌科收治住院的45例(63枚)經(jīng)細(xì)針穿刺抽吸活檢篩查診斷的甲狀腺良性結(jié)節(jié)患者(TI-RADS分類1-3類,Bethesda分類Ⅱ類),微波消融后隨訪3月進(jìn)行分析。做出下列評價:(1)總體療效評價:通過比較術(shù)前后結(jié)節(jié)經(jīng)線、體積及血流信號改變,甲狀腺相關(guān)指標(biāo)的改變及并發(fā)癥來評價其療效;(2)亞組評價:按結(jié)節(jié)內(nèi)部回聲的不同(在細(xì)針穿刺抽吸活檢篩查出良性結(jié)節(jié)基礎(chǔ)上分為囊性、囊實性、實性)分別比較術(shù)后結(jié)節(jié)體積、甲狀腺相關(guān)指標(biāo)的變化情況來探討微波消融對不同性質(zhì)、體積結(jié)節(jié)治療的差異性;(3)影響因素評價:比較代謝及甲狀腺相關(guān)指標(biāo)對其療效的影響。研究結(jié)果1.微波消融治療甲狀腺良性結(jié)節(jié)的療效比較結(jié)果結(jié)果表明,微波消融后結(jié)節(jié)體積呈持續(xù)縮小趨勢,術(shù)后1月體積明顯縮小,至術(shù)后3月平均體積縮小率達(dá)到71.60%,具有顯著統(tǒng)計學(xué)意義(P0.0001)。結(jié)節(jié)內(nèi)部或邊緣超聲血流信號顯示術(shù)后1天即明顯消減(P0.001),至術(shù)后3月52.46%結(jié)節(jié)血流信號可完全消失。術(shù)前后甲狀腺功能及甲狀腺自身抗體比較并無統(tǒng)計學(xué)差異。治療過程中所有患者均能耐受并完成治療,出現(xiàn)術(shù)中疼痛(31.1%)、聲音嘶啞(20%)、出血(20%),大部分癥狀在術(shù)后24小時內(nèi)得到消減,1例患者術(shù)后3月聲嘶癥狀完全緩解,全程均未予以特殊處理。2.微波消融治療甲狀腺良性結(jié)節(jié)的亞組間療效比較結(jié)果術(shù)后囊實性結(jié)節(jié)、實性結(jié)節(jié)及囊性結(jié)節(jié)之間的平均體積縮小率均存在統(tǒng)計學(xué)意義,其中囊實性結(jié)節(jié)縮小最為顯著(平均體積縮小率為63.29%);對結(jié)節(jié)體積變化進(jìn)行分析,發(fā)現(xiàn)至隨訪末期不同大小的結(jié)節(jié)體積均縮小,但體積1ml的結(jié)節(jié)體積變化(體積變化率)均不顯著。3.影響因素評價結(jié)果初步比較了代謝及甲狀腺相關(guān)指標(biāo)對微波消融治療甲狀腺良性結(jié)節(jié)的療效影響,顯示ALT、AST、TC、CREA及TSH值越高,結(jié)節(jié)體積變化(體積變化率)越小,HDL-C、FT4、TT4與體積變化(體積變化率)則呈正相關(guān)表現(xiàn),而血壓、血糖與之無明顯相關(guān)性。研究結(jié)論綜上所述,微波消融作為一類熱消融技術(shù)應(yīng)用于甲狀腺良性結(jié)節(jié)治療中具有明確的療效性和安全性。微波消融均能顯著縮小不同性質(zhì)及體積較大的結(jié)節(jié),對于囊實性結(jié)節(jié),微波消融可能存在一定的優(yōu)越性;而針對小體積的甲狀腺結(jié)節(jié),尤其是體積1ml的結(jié)節(jié),微波消融范圍可能超過結(jié)節(jié),如需微創(chuàng)治療可以優(yōu)先選擇激光消融。微波消融嚴(yán)重的并發(fā)癥是損傷神經(jīng),如果操作合理,嚴(yán)格遵循治療規(guī)范,結(jié)合超聲引導(dǎo)下定位準(zhǔn)確,其發(fā)生率明顯下降,同時我們也需注意:對位置靠近神經(jīng)的結(jié)節(jié),能量的釋放盡量避開神經(jīng)處,可考慮不完全消融。血脂、肝腎功損害及TSH等因素可負(fù)面干預(yù)治療后甲狀腺良性結(jié)節(jié)的體積縮小,從而影響其療效。研究背景作為過氧化物酶體增殖物激活受體γ(peroxisome proliferator activatedreceptor-γ,PPAR-γ)激動劑,噻唑烷二酮(thiazolidinedione,TZD)主要通過增加外周組織中的胰島素敏感性來降低血糖,該類藥物已廣泛用于糖尿病的治療。研究發(fā)現(xiàn),吡格列酮除了降低血糖,還可以預(yù)防主要心血管病、酒精性脂肪性肝炎,表明其臨床應(yīng)用有更廣泛的前景。但是,近年來的一系列大樣本研究顯示不一致的結(jié)果,引發(fā)了全球關(guān)于吡格列酮與膀胱癌風(fēng)險的眾多爭議。研究目的為了尋求關(guān)于這個爭議問題的原因,我們進(jìn)行了分層分析,以探討導(dǎo)致先前研究不一致結(jié)果的潛在混雜因素。數(shù)據(jù)來源Embase,Pub Med,Web of Science,Cochrane Central Register of Controlled Trials和Clinical Trials.gov。搜索時間為從數(shù)據(jù)庫建立至2017年1月5日。研究選擇包括與吡格列酮和糖尿病患者的癌癥相關(guān)的所有研究(觀察性研究observational study,OB和隨機對照試驗randomized controlled trial,RCT)。數(shù)據(jù)提取研究組成員進(jìn)行了文獻(xiàn)檢索、數(shù)據(jù)提取和質(zhì)量評估研究。分析目標(biāo)主要分析吡格列酮和膀胱癌風(fēng)險之間的關(guān)聯(lián)是否因研究設(shè)計(即研究類型、調(diào)整因素、干預(yù)措施、比較劑、隨訪持續(xù)時間和研究人群)而不同。次要分析是評估吡格列酮和其它癌癥風(fēng)險之間的關(guān)系。結(jié)果來自觀察性研究的2,764,731名受試者和來自隨機對照試驗的9,999名受試者的資料被用于鑒定吡格列酮和膀胱癌風(fēng)險的分析。對于觀察性研究,膀胱癌風(fēng)險在全球水平的合并比值比(odds ratio,OR)為1.15(95%置信區(qū)間confidence interval,CI,1.07 1.24;P0.001)。潛在混雜因素分層分析顯示,研究類型、年齡/性別、治療持續(xù)時間、累積劑量、對照組中使用的藥物、平均隨訪期和研究人群區(qū)域可能與結(jié)果的不一致有關(guān)。對于人群而言,歐洲人群中吡格列酮增加了膀胱癌風(fēng)險(OR,1.20;95%CI,1.08-1.32;P0.001),而在美國(OR,1.03;95%CI,0.88-1.21;P=0.68)和亞洲人群(OR,1.16;95%CI,0.96-1.40;P=0.12)中沒有增加膀胱癌風(fēng)險。此外,在美國和亞洲地區(qū),根據(jù)潛在混雜因素分層分析的結(jié)果也是陰性的(P0.05)。而在歐洲地區(qū),除了未調(diào)整年齡/性別,吸煙,治療持續(xù)時間和隨訪時間較短,和對照組使用羅格列酮的亞組外(P0.05),分層研究的結(jié)果也都是陽性的(P0.05)。綜合觀察性研究和隨機對照試驗,所有結(jié)果與在觀察性研究中報道的結(jié)果類似。此外,吡格列酮與前列腺癌和胰腺癌的風(fēng)險增加相關(guān)(P0.05),而與肝癌和腦癌的風(fēng)險降低相關(guān)(P0.05)。結(jié)論和相關(guān)性吡格列酮與膀胱癌的風(fēng)險需要根據(jù)不同的人群區(qū)域考慮。這一風(fēng)險可能存在于歐洲,但不存在于美國和亞洲人群。在歐洲,治療時間較長(12個月)或累積劑量的較大(28,000 mg)的患者需要更多的注意,而且吡格列酮的長期影響(≥3.6年)需要了解。并且,在將來的相關(guān)研究中應(yīng)調(diào)整年齡/性別和吸煙狀況,并在對照組中采用非特異性藥物。此外,吡格列酮也可能涉及其它癌癥。
[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.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R581

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