內(nèi)鏡超聲在早期食管癌診斷和治療中的應(yīng)用

劉宇亭　徐　燦　李兆申

第二軍醫(yī)大學(xué)附屬長(zhǎng)海醫(yī)院消化內(nèi)科(200433)

內(nèi)鏡超聲在早期食管癌診斷和治療中的應(yīng)用

劉宇亭徐燦李兆申*

第二軍醫(yī)大學(xué)附屬長(zhǎng)海醫(yī)院消化內(nèi)科(200433)

早期食管癌是指來(lái)源于黏膜層和黏膜下層無(wú)淋巴結(jié)轉(zhuǎn)移的食管癌，一般無(wú)明顯臨床癥狀，多在內(nèi)鏡檢查或體檢時(shí)發(fā)現(xiàn)。當(dāng)前以內(nèi)鏡下治療為主，包括內(nèi)鏡下黏膜切除術(shù)(EMR)和內(nèi)鏡黏膜下剝離術(shù)(ESD)，術(shù)后5年生存率可達(dá)90%以上。一旦患者出現(xiàn)癥狀，則多伴局部淋巴結(jié)轉(zhuǎn)移，治療效果欠佳，此時(shí)術(shù)后5年生存率降至27.0%~43.6%[1]。因此，早期診斷、早期治療對(duì)提高患者生存率尤為關(guān)鍵。

隨著內(nèi)鏡技術(shù)的發(fā)展，尤其是內(nèi)鏡超聲(EUS)技術(shù)日益成熟，使早期食管癌的檢出率大幅提高。EUS是集超聲和內(nèi)鏡為一體的檢查手段，彌補(bǔ)了普通內(nèi)鏡無(wú)法探及病變浸潤(rùn)深度以及無(wú)法了解淋巴結(jié)轉(zhuǎn)移情況的缺陷。EUS下早期食管癌的圖像表現(xiàn)為管壁黏膜層增厚、層次紊亂、中斷以及各層次分界消失、較小的不規(guī)則低回聲影[2]。EUS引導(dǎo)下細(xì)針穿刺活檢術(shù)(EUS-FNA)對(duì)診斷局部淋巴結(jié)轉(zhuǎn)移的敏感性和特異性均較高。本文就 EUS在早期食管癌診斷和治療中的應(yīng)用作一綜述。

一、早期食管癌術(shù)前分期

正確的TNM分期與治療方案的選擇、預(yù)后評(píng)估以及放化療療效的預(yù)測(cè)均密切相關(guān)，早期食管癌若局限于黏膜層和黏膜下層，多選擇EMR或ESD，否則多以外科手術(shù)結(jié)合放化療為主。EMR具有診斷和治療的雙重作用，術(shù)后可從病變標(biāo)本中檢查腫瘤浸潤(rùn)深度以及切除是否徹底，主要適用于黏膜內(nèi)癌，最佳部位是食管中下段后側(cè)壁，其適應(yīng)證較為相對(duì)。隨著設(shè)備改進(jìn)以及經(jīng)驗(yàn)積累，EMR治療范圍可拓寬。黏膜下癌是EMR的禁忌證，而ESD擴(kuò)大了EMR的適應(yīng)證范圍，具有較高的整塊切除率，可減少病灶殘留和復(fù)發(fā)，達(dá)到對(duì)早期消化道腫瘤根治性切除[3]。EUS-FNA可對(duì)可疑病變進(jìn)行穿刺活檢，獲得組織學(xué)依據(jù)，有助于對(duì)疾病分期的判斷。

1. EUS在早期食管癌術(shù)前分期中的應(yīng)用：食管癌TNM分期是評(píng)價(jià)預(yù)后的重要指標(biāo)，EUS可顯示食管壁黏膜層、黏膜肌層、黏膜下層、固有肌層、外膜層五層結(jié)構(gòu)。早期食管癌在EUS下的典型表現(xiàn)為局限于黏膜層且不超過(guò)黏膜下層的低回聲病灶。EUS亦可清晰顯示大部分縱隔淋巴結(jié)、腹腔淋巴結(jié)。因此，EUS在食管癌T、N分期中扮演重要角色，主要用于確定腫瘤浸潤(rùn)深度以及有無(wú)淋巴結(jié)轉(zhuǎn)移。EUS通過(guò)顯示食管壁的層次結(jié)構(gòu)判斷食管原發(fā)腫瘤的浸潤(rùn)深度，對(duì)食管癌T分期的準(zhǔn)確性可達(dá)79%~92%[4-5]。EUS下食管癌T分期可概括為Tx期：原發(fā)腫瘤無(wú)法評(píng)價(jià)；T0期：無(wú)原發(fā)腫瘤證據(jù)；Tis期：原位癌；T1期：腫瘤侵及黏膜層或部分黏膜下層；T2期：腫瘤侵及固有肌層；T3期：腫瘤侵及漿膜層，累及食管全層；T4期：腫瘤侵及食管壁全層并突破食管外膜，侵犯主動(dòng)脈，管壁外周可見腫大淋巴結(jié)[6]。

van Vliet等[7]的研究指出，EUS檢測(cè)食管癌腹腔淋巴結(jié)轉(zhuǎn)移的敏感性和特異性分別為85%和96%，診斷標(biāo)準(zhǔn)為直徑大于1 cm的類圓形低回聲，邊緣銳利。當(dāng)EUS發(fā)現(xiàn)局部淋巴結(jié)腫大時(shí)，應(yīng)行FNA確診。EUS和CT均可用于腹部淋巴結(jié)檢查，EUS主要探查有無(wú)腹腔淋巴結(jié)轉(zhuǎn)移，CT可用于檢查有無(wú)其他腹部淋巴結(jié)轉(zhuǎn)移。與CT和PET-CT相比，EUS診斷淋巴結(jié)轉(zhuǎn)移的敏感性具有顯著優(yōu)勢(shì)，但特異性相對(duì)不足[8-9]。由于超聲波穿透力有限，EUS對(duì)食管癌遠(yuǎn)處轉(zhuǎn)移的檢測(cè)作用有限，此時(shí)應(yīng)選CT、MR或PET-CT等影像學(xué)檢查。但EUS能測(cè)及肝左葉不足1 cm的微小轉(zhuǎn)移灶以及腹腔干淋巴結(jié)，并可進(jìn)行穿刺活檢，因此在食管癌遠(yuǎn)處轉(zhuǎn)移的評(píng)價(jià)中亦具有獨(dú)特作用。

行EUS檢查時(shí)同步行EUS-FNA被越來(lái)越多的醫(yī)師所親睞，其優(yōu)勢(shì)在于行常規(guī)EUS的同時(shí)可獲取可疑病灶的組織病理學(xué)標(biāo)本，以明確腫大淋巴結(jié)是否為腫瘤侵犯。判斷N分期時(shí)，EUS-FNA結(jié)果優(yōu)于普通EUS檢查，在已行EUS-FNA的基礎(chǔ)上再行PET-CT并不能進(jìn)一步提高N分期的準(zhǔn)確性[10-12]。但需注意的是，EUS-FNA具有一定的假陰性率。

2. EUS與CT和PET-CT在術(shù)前分期中的比較：對(duì)于食管病變侵犯深度和周圍淋巴結(jié)轉(zhuǎn)移的判斷，EUS的準(zhǔn)確率優(yōu)于CT，可達(dá)80%~90%[13]。但除腹腔干周圍淋巴結(jié)外，EUS診斷遠(yuǎn)處轉(zhuǎn)移的敏感性較差。一般認(rèn)為，CT、MR、PET-CT對(duì)于腫瘤早期診斷意義不大。在N分期方面，EUS優(yōu)于PET-CT[14-16]，后者評(píng)估淋巴結(jié)轉(zhuǎn)移的準(zhǔn)確性不高，如淋巴結(jié)緊鄰高代謝的腫瘤實(shí)質(zhì)時(shí)，PET-CT易漏診，且不能用于檢測(cè)微 小病變，但診斷遠(yuǎn)處轉(zhuǎn)移的準(zhǔn)確性較高[7,17]。Keswani等[6]的研究顯示，在92例食管癌患者中，經(jīng)EUS確診腹腔淋巴結(jié)轉(zhuǎn)移17例，其中7例經(jīng)EUS-FNA證實(shí)腫瘤淋巴結(jié)浸潤(rùn)，僅2例經(jīng)PET-CT確診腹腔淋巴結(jié)轉(zhuǎn)移。一項(xiàng)系統(tǒng)性回顧[18]顯示，PET-CT對(duì)食管癌局部轉(zhuǎn)移的敏感性和特異性均一般，而對(duì)遠(yuǎn)處轉(zhuǎn)移的敏感性和特異性較理想。因此，對(duì)于高度懷疑遠(yuǎn)處轉(zhuǎn)移的患者應(yīng)首選PET-CT檢查。然而，PET-CT的空間分辨率較低，限制了對(duì)較小淋巴結(jié)的檢測(cè)。另一項(xiàng)研究[19]顯示，通過(guò)EUS檢查發(fā)現(xiàn)局部縱隔淋巴結(jié)轉(zhuǎn)移的大部分食管癌患者，經(jīng)PET-CT掃描后證實(shí)僅一小部分有淋巴結(jié)轉(zhuǎn)移，因此尚未明確是否將PET-CT作為常規(guī)檢查[6]。在N分期中，PET-CT僅推薦用于不能完成EUS檢查的患者。

Lowe等[16]對(duì)75例新發(fā)食管癌患者進(jìn)行分析研究，對(duì)比EUS、CT、PET-CT在食管癌分期中的診斷價(jià)值，結(jié)果顯示在T分期中，EUS的準(zhǔn)確率為71%，相比CT、PET-CT的43%具有明顯優(yōu)勢(shì)。對(duì)于淋巴結(jié)轉(zhuǎn)移，三者的敏感性和特異性相似，而對(duì)于遠(yuǎn)處轉(zhuǎn)移，PET-CT的優(yōu)勢(shì)更為明顯。然而，亦有報(bào)道[20-21]指出，對(duì)于淋巴結(jié)轉(zhuǎn)移，EUS的敏感性和準(zhǔn)確性顯著高于CT和PET-CT。由此可見，EUS、CT、PET-CT在診斷食管癌分期中扮演不同角色，各有優(yōu)勢(shì)，不能相互替代，在臨床中應(yīng)將其結(jié)合應(yīng)用。同樣，三種方法亦有缺陷，如EUS僅能發(fā)現(xiàn)位于食管或胃壁附近的腫大淋巴結(jié)，不易發(fā)現(xiàn)遠(yuǎn)處淋巴結(jié)或器官轉(zhuǎn)移[22]；CT不能探測(cè)及正常大小的淋巴結(jié)，且不能鑒別腫大淋巴結(jié)是腫瘤轉(zhuǎn)移亦或炎性增大；PET-CT對(duì)直徑小于1 cm的病灶可能漏診[20]。在食管癌早期診斷中是否推薦PET-CT尚未明確，盡管PET-CT是確診遠(yuǎn)處轉(zhuǎn)移的最佳非侵入性檢查，但研究[23]顯示僅有少數(shù)食管癌患者可經(jīng)PET-CT確診遠(yuǎn)處轉(zhuǎn)移。Feith等[24]的研究顯示，經(jīng)PET-CT確診的遠(yuǎn)處轉(zhuǎn)移患者在行EUS檢查時(shí)均發(fā)現(xiàn)有淋巴結(jié)轉(zhuǎn)移。研究[6,25]認(rèn)為，EUS可應(yīng)用于所有食管癌患者，而PET-CT可用于已確診有淋巴結(jié)浸潤(rùn)或無(wú)法進(jìn)行EUS檢查的患者。

二、EUS在早期食管癌評(píng)估中的可靠性和爭(zhēng)議

EUS評(píng)估早期食管癌的可靠性與病變類型、位置、術(shù)者經(jīng)驗(yàn)、超聲探頭頻率以及其他影像學(xué)輔助檢查有關(guān)，病例異質(zhì)性亦可造成EUS評(píng)估差異。He等[26]的研究顯示，EUS診斷食管癌的準(zhǔn)確性與病變的部位和長(zhǎng)度密切相關(guān)。Thosani等[27]指出，采用高頻率小探頭時(shí)，EUS的敏感性、特異性、陽(yáng)性似然比、陰性似然比以及診斷比值比更高。此外，Young 等[28]的研究顯示，在Barrett食管患者中，EUS對(duì)早癌和高級(jí)別瘤變T分期的準(zhǔn)確性僅為65%。EUS對(duì)不同部位病變檢查的準(zhǔn)確性亦不相同，Chemaly等[29]的研究顯示，病變位于食管近段和中段時(shí)，EUS分期的準(zhǔn)確性為87.1%，而位于食管遠(yuǎn)端時(shí)則為47.6%，此反映了EUS在臨床應(yīng)用中的局限性。Young等[28]的研究表明，對(duì)于高級(jí)別瘤變以及黏膜內(nèi)腺癌的T分期，EUS的準(zhǔn)確性較欠缺，需進(jìn)一步行EMR獲取病理組織確診。研究[26,28]顯示，EUS診斷T分期的亞型分期(如T1、T2)的準(zhǔn)確性僅為70%，進(jìn)一步提示EUS并非高級(jí)別瘤變和黏膜內(nèi)腺癌的必需檢查，甚至有誤診傾向。但有研究者[30-31]提出，EMR可用于早期Barrett相關(guān)食管腺癌的臨床分期和治療。

盡管EUS在食管癌治療方式的選擇中發(fā)揮重要作用，但一些研究[29,32-35]亦提出其并非是診斷黏膜以及黏膜下病變的最佳選擇，而診斷性內(nèi)鏡下切除術(shù)(ER)才是早癌術(shù)前檢查的最佳手段，其可提供大塊完整組織，從而得到準(zhǔn)確的組織病理學(xué)診斷。由于ER比EUS能提供更準(zhǔn)確的組織學(xué)信息，因此對(duì)早期食管癌行EUS檢查的必要性亦存在一定爭(zhēng)議[28,36]。此外，食管切除術(shù)仍是大多數(shù)早期食管癌患者的標(biāo)準(zhǔn)治療方案[37]。

三、結(jié)語(yǔ)

EUS已廣泛應(yīng)用于早期食管癌的診斷、分期以及手術(shù)方式選擇等多個(gè)環(huán)節(jié)，如根據(jù)T分期，若病變局限于黏膜層和黏膜下層，多選擇EMR或ESD，其余則多以外科手術(shù)結(jié)合放化療為主。在N分期中，應(yīng)結(jié)合CT和PET-CT判斷有無(wú)局部和遠(yuǎn)處淋巴結(jié)轉(zhuǎn)移，必要時(shí)結(jié)合FNA以獲取組織學(xué)標(biāo)本。EUS對(duì)早期食管癌的T分期以及局部淋巴結(jié)轉(zhuǎn)移的診斷優(yōu)于CT和PET-CT，而后者對(duì)遠(yuǎn)處轉(zhuǎn)移的敏感性和特異性均高于EUS，三種檢查扮演著不同角色，必要時(shí)應(yīng)聯(lián)合應(yīng)用。目前，EUS對(duì)于早期食管癌的診斷價(jià)值尚存爭(zhēng)議，因此，在肯定EUS作用的同時(shí)，臨床醫(yī)師應(yīng)注意EUS對(duì)不同腫瘤類型、病灶部位檢查的局限性。此外，在臨床應(yīng)用中，EUS的診斷效率與醫(yī)療中心的規(guī)模、實(shí)施EUS檢查的數(shù)量以及術(shù)者經(jīng)驗(yàn)等因素密切相關(guān)。

四、展望

由于準(zhǔn)確的TNM分期對(duì)食管癌治療方式的選擇至關(guān)重要，因此如何提高EUS對(duì)食管癌分期的準(zhǔn)確性是當(dāng)前面臨的一項(xiàng)主要挑戰(zhàn)，而EUS-FNA亦已成為提高診斷淋巴結(jié)轉(zhuǎn)移的特異性和準(zhǔn)確性的有效手段。隨著對(duì)早期食管癌診斷和治療的不斷認(rèn)識(shí)、診治技術(shù)的不斷發(fā)展以及內(nèi)鏡醫(yī)師技術(shù)水平的不斷提高。相信不久的將來(lái)，食管癌早期診斷、早期治療水平會(huì)得到顯著提高。

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摘要早期食管癌是指來(lái)源于黏膜層和黏膜下層無(wú)淋巴結(jié)轉(zhuǎn)移的食管癌，一般無(wú)明顯臨床癥狀，多在內(nèi)鏡檢查或體檢時(shí)發(fā)現(xiàn)。早期食管癌以內(nèi)鏡下治療為主，術(shù)后5年生存率可達(dá)90%以上。一旦患者出現(xiàn)癥狀，則多伴局部淋巴結(jié)轉(zhuǎn)移，治療效果欠佳，5年生存率顯著降低。因此，食管癌的早期診斷、早期治療對(duì)于提高患者生存率至關(guān)重要。隨著內(nèi)鏡技術(shù)的發(fā)展，尤其是內(nèi)鏡超聲(EUS)的日益成熟，使早期食管癌的檢出率大幅提高。此外，EUS亦在早期食管癌術(shù)前分期中扮演重要角色。本文就 EUS在早期食管癌診斷和治療中的應(yīng)用作一綜述。

關(guān)鍵詞食管腫瘤；腔內(nèi)超聲檢查；腫瘤分期；內(nèi)鏡治療

Application of Endoscopic Ultrasonography in Diagnosis and Treatment of Early Esophageal CancerLIUYuting,XUCan,LIZhaoshen.DepartmentofGastroenterology,ChanghaiHospital,theSecondMilitaryMedicalUniversity,Shanghai(200433)

Correspondence to: LI Zhaoshen, Email: zhsli@81890.net

AbstractEarly esophageal cancer is derived from mucosa and submucosa without lymph node metastasis. They are detected generally during endoscopy or physical examination without clinical symptoms. Main treatment of early esophageal cancer is endoscopic resection, and the 5-year survival rate is over 90%. Once symptoms occur, local lymph node metastasis is often present and the prognosis is poor with a markedly reduced 5-year survival rate. Thus it is vital to diagnose and treat esophageal cancer at an early stage. With the development of endoscopic techniques, especially the proficiency of endoscopic ultrasonography (EUS), the detection rate of early esophageal cancer has been increased greatly. EUS also plays an important role in the staging of early esophageal cancer. This article reviewed the application of EUS in diagnosis and treatment of early esophageal cancer.

Key wordsEsophageal Neoplasms;Endosonography;Neoplasm Staging;Endoscopic Therapy

通信作者*本文，Email: zhsli@81890.net

DOI:10.3969/j.issn.1008-7125.2015.08.011