胸段食管鱗癌頸淋巴轉(zhuǎn)移診治進(jìn)展*

王海軍 綜述， 韓泳濤 審校

646000 四川 瀘州，西南醫(yī)科大學(xué)(王海軍，韓泳濤)；610041成都，四川省腫瘤醫(yī)院·研究所，四川省癌癥防治中心，電子科技大學(xué)醫(yī)學(xué)院 胸外科(韓泳濤)

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胸段食管鱗癌頸淋巴轉(zhuǎn)移診治進(jìn)展*

王海軍 綜述， 韓泳濤△審校

646000 四川 瀘州，西南醫(yī)科大學(xué)(王海軍，韓泳濤)；610041成都，四川省腫瘤醫(yī)院·研究所，四川省癌癥防治中心，電子科技大學(xué)醫(yī)學(xué)院 胸外科(韓泳濤)

食管癌惡性程度高、預(yù)后差。淋巴結(jié)轉(zhuǎn)移及陽(yáng)性淋巴結(jié)數(shù)量是影響患者預(yù)后的重要原因之一，尤其頸淋巴結(jié)和喉返神經(jīng)旁淋巴結(jié)是一直研究爭(zhēng)議的熱點(diǎn)。雖然頸胸腹三野淋巴結(jié)清掃術(shù)較胸腹兩野淋巴結(jié)清掃術(shù)可以延長(zhǎng)患者生存時(shí)間并減少?gòu)?fù)發(fā)，但是，該種術(shù)式在使患者生存獲益的同時(shí)也帶來(lái)了術(shù)后高并發(fā)癥。頸淋巴結(jié)是否存在轉(zhuǎn)移直接影響著淋巴結(jié)清掃范圍，雖然可以通過(guò)多種方法診斷頸淋巴結(jié)有無(wú)轉(zhuǎn)移，但是敏感性及特異性低。喉返神經(jīng)旁淋巴結(jié)被認(rèn)為是食管癌的前哨淋巴結(jié)，用于預(yù)測(cè)頸淋巴結(jié)是否存在轉(zhuǎn)移，然而準(zhǔn)確率不超過(guò)50%。本文將對(duì)目前食管癌頸淋巴轉(zhuǎn)移診治現(xiàn)狀進(jìn)行綜述。

食管癌； 淋巴結(jié)清掃； 頸淋巴結(jié)； 超聲； 前哨淋巴結(jié)

食管癌是引起全球腫瘤相關(guān)死亡的重要原因之一，其惡性程度高，預(yù)后差。食管鱗狀細(xì)胞癌是中國(guó)及日本等亞洲國(guó)家的主要病理類型，發(fā)病率占所有病理類型的90%以上，主要發(fā)生于胸段食管。腫瘤切除+根治性淋巴結(jié)清掃目前仍是可切除鱗癌患者的首選方案，5年生存率約為15%～25%。術(shù)后復(fù)發(fā)和轉(zhuǎn)移是導(dǎo)致患者高死亡率的主要原因，而頸淋巴結(jié)轉(zhuǎn)移和復(fù)發(fā)是影響患者預(yù)后的重要因素[1-3]。雖然在胸腹二野淋巴結(jié)清掃術(shù)(two-field lymphadenectomy,2-FL)基礎(chǔ)上擴(kuò)大淋巴結(jié)清掃范圍即頸胸腹三野淋巴結(jié)清掃術(shù)(three-field lymphadenectomy,3-FL)可以提高患者的生存率并降低復(fù)發(fā)率，但是與2-FL相比，3-FL術(shù)后吻合口瘺、喉返神經(jīng)損傷等并發(fā)癥發(fā)生率隨之增加[4-5]。因此，為避免由于擴(kuò)大化手術(shù)對(duì)3-FL非獲益人群帶來(lái)的各種負(fù)面效應(yīng)，篩選出3-FL的獲益人群非常重要。目前，大多數(shù)食管胸段鱗癌患者選擇2-FL或3-FL的主要參照標(biāo)準(zhǔn)之一是術(shù)前頸淋巴結(jié)狀態(tài)，術(shù)前檢查懷疑或病理證實(shí)頸淋巴結(jié)轉(zhuǎn)移時(shí)選擇3-FL，反之則選擇2-FL[4,6]。由此可知，術(shù)前準(zhǔn)確預(yù)測(cè)頸淋巴結(jié)是否存在轉(zhuǎn)移十分關(guān)鍵。盡管超聲(ultrasonography)、CT(computed tomography)及PET-CT(positron emission tomography-CT)及MRI(magnetic resonance imaging)等無(wú)創(chuàng)檢查和超聲內(nèi)鏡(endoscopic ultrasound,EUS)及內(nèi)鏡引導(dǎo)下細(xì)針穿刺活檢(endoscopic ultrasonography-guided fine needle aspiration,EUS-FNA)等有創(chuàng)方法都已被用于術(shù)前鑒別頸淋巴結(jié)良惡性，但是對(duì)于較小轉(zhuǎn)移淋巴結(jié)及微轉(zhuǎn)移淋巴結(jié)診斷能力有限[7-10]。胸內(nèi)喉返神經(jīng)旁淋巴結(jié)曾被部分學(xué)者作為前哨淋巴結(jié)預(yù)測(cè)食管癌頸淋巴結(jié)是否存在轉(zhuǎn)移，但由于食管癌淋巴引流方式復(fù)雜多樣、存在跳躍轉(zhuǎn)移等特點(diǎn)限制了喉返神經(jīng)旁淋巴結(jié)的預(yù)測(cè)作用。因此，胸內(nèi)喉返神經(jīng)旁淋巴結(jié)是否可以成為食管鱗癌的前哨淋巴結(jié)目前仍沒(méi)有定論[11-13]。鑒于以上現(xiàn)狀，本文將從食管癌三野淋巴結(jié)清掃研究現(xiàn)狀、食管癌頸淋巴結(jié)轉(zhuǎn)移診斷現(xiàn)狀和食管癌前哨淋巴結(jié)研究現(xiàn)狀三方面對(duì)食管胸段鱗癌頸淋巴轉(zhuǎn)移相關(guān)熱點(diǎn)問(wèn)題進(jìn)行綜述(注：文中所提及喉返神經(jīng)旁淋巴結(jié)均指胸內(nèi)喉返神經(jīng)旁淋巴結(jié))

1 食管胸段鱗癌三野淋巴結(jié)清掃研究現(xiàn)狀

復(fù)發(fā)和轉(zhuǎn)移是導(dǎo)致食管鱗癌術(shù)后患者死亡的主要原因[14]。頸淋巴結(jié)有無(wú)轉(zhuǎn)移是影響患者預(yù)后的重要因素之一。已報(bào)道的食管癌頸淋巴結(jié)轉(zhuǎn)移率高達(dá)20%～60%[14-19]。因此，為降低術(shù)后復(fù)發(fā)率并延長(zhǎng)患者生存時(shí)間，有必要擴(kuò)大淋巴結(jié)清掃范圍行頸淋巴結(jié)清掃。目前食管胸段鱗癌淋巴結(jié)清掃術(shù)式主要包括胸腹二野淋巴結(jié)清掃術(shù)(2-FL)和頸胸腹三野淋巴結(jié)清掃術(shù)(3-FL)，3-FL在2-FL基礎(chǔ)上進(jìn)一步清掃雙頸部淋巴結(jié)。雖然3-FL較2-FL有降低術(shù)后頸淋巴結(jié)復(fù)發(fā)甚至提高生存率的優(yōu)點(diǎn)，但同時(shí)也存在創(chuàng)傷大、并發(fā)癥高等缺點(diǎn)。綜上所述，選擇3-FL的獲益人群十分重要，也是當(dāng)代精準(zhǔn)治療理念的要求。

1.1 三野淋巴結(jié)清掃術(shù)與兩野清掃術(shù)的預(yù)后比較

相關(guān)研究報(bào)道，食管鱗癌患者3-FL術(shù)后5年總生存率為41.9%～73.2%[4,5,17,20-21]，2-FL 術(shù)后5年總生存率為33.7%～48.7%[22-24]。Kato等[22]早期的隨機(jī)對(duì)照研究將150例胸段食管癌患者隨機(jī)分組后分別接受3-FL和2-FL手術(shù)，其中鱗癌患者138例，術(shù)后總的5年生存率3-FL組和2-FL組分別為48.7%和 33.7%(P<0.01)。Kato等[25]后期報(bào)道胸段食管癌患者3-FL與2-FL術(shù)后局部復(fù)發(fā)率分別為17% 和 38%[25]。Akiyama等[23]比較了717例食管胸段鱗癌患者分別接受3-FL與2-FL 術(shù)的預(yù)后情況，術(shù)后總的5年生存率3-FL組與2-FL 組分別為55.0% 與 38.3%(P=0.0013)。Nishihira等[24]后來(lái)進(jìn)行的前瞻性研究共納入62例食管胸段鱗癌患者，隨機(jī)分配到3-FL組(32例)和2-FL組(30例)，3-FL組與2-FL組術(shù)后5年生存率和復(fù)發(fā)率分別為66.2% vs.48.0% 與19.9% vs. 24.1%，雖然3-FL組較2-FL組更有提高生存率并降低復(fù)發(fā)率的趨勢(shì)，但是均未達(dá)到統(tǒng)計(jì)學(xué)差異。Ma等[6]最近報(bào)道的一項(xiàng)meta分析包括超過(guò)7 000例食管癌患者，結(jié)果顯示3-FL組較2-FL組具有明顯的生存優(yōu)勢(shì)(3年生存率：RR=1.44,95%CI:1.19～1.75,P<0.01；5年生存率：RR=1.37,95%CI:1.18～1.59,P<0.01)。另一項(xiàng)meta分析也得出相似的結(jié)論[26]。雖然也有少數(shù)研究認(rèn)為3-FL較2-FL并未顯示出明顯優(yōu)勢(shì)[27-28]。但從總體看，3-FL較2-FL在食管胸段鱗癌患者的優(yōu)勢(shì)已逐漸形成共識(shí)。并發(fā)癥方面，食管胸段鱗癌患者3-FL術(shù)后死亡率為1.2%～6.4%，肺部并發(fā)癥1.5%～31.3%，吻合口瘺1.5%～38.6%，喉返神經(jīng)損傷2.6%～28% ；2-FL術(shù)后死亡率為6%～10.7%，肺部并發(fā)癥0%～13.9%，吻合口瘺6.4%～29.1%，喉返神經(jīng)損傷0～23.1%[4-5,17,20-21]。雖然3-FL比2-FL并發(fā)癥發(fā)生率高，但隨著醫(yī)學(xué)的發(fā)展，尤其是對(duì)患者圍手術(shù)期管理水平的提高、微創(chuàng)技術(shù)和機(jī)器人手術(shù)等新技術(shù)的逐漸開(kāi)展及推廣，手術(shù)對(duì)患者的創(chuàng)傷越來(lái)越小，術(shù)后各種并發(fā)癥也較傳統(tǒng)開(kāi)放手術(shù)明顯降低[4]。

1.2 三野淋巴結(jié)清掃的選擇標(biāo)準(zhǔn)

雖然3-FL較2-FL可使食管胸段鱗癌患者獲益，但術(shù)后并發(fā)癥發(fā)生率高。是否3-FL適合所有食管胸段鱗癌患者一直存在爭(zhēng)議，而篩選出3-FL獲益人群至關(guān)重要。由于胸上段食管在解剖學(xué)上最靠近頸部，并且食管胸上段鱗癌患者比中下段患者發(fā)生頸淋巴結(jié)轉(zhuǎn)移風(fēng)險(xiǎn)更高[16,29-30]。因此，許多研究認(rèn)為3-FL適用于食管胸上段鱗癌患者[6,18,31-32]。Fujita等[31]比較了128例食管胸段鱗癌患者中3-FL組(63例)與2-FL組(65例)的預(yù)后情況，腫瘤分布包括上段11例、中段97例、下段38例。3-FL組與2-FL組術(shù)后5年生存率分別為40%和36%(P>0.05)，術(shù)后死于復(fù)發(fā)的比例為3-FL組33%和2-FL組51%(P<0.05)。生存分析結(jié)果顯示對(duì)于中上段腫瘤伴淋巴結(jié)陽(yáng)性患者，3-FL組較2-FL組具明顯生存優(yōu)勢(shì)(P<0.05)，對(duì)于下段或淋巴結(jié)陰性患者兩組間無(wú)明顯生存差異。Udagawa等[18]評(píng)價(jià)了906例胸段食管癌患者行3-FL術(shù)的預(yù)后情況，他們認(rèn)為3-FL是食管中上段鱗癌患者的標(biāo)準(zhǔn)淋巴結(jié)清掃方案。Ma等[6]和Ye等[26]的meta分析也顯示3-FL的獲益人群主要為食管胸中上段鱗癌患者，尤其是同時(shí)伴有淋巴結(jié)轉(zhuǎn)移者。Tachimori等[32]最近報(bào)道了3 827例食管鱗癌患者3-FL術(shù)后的情況，包括上段983例、中段2 215例、下段629例，上、中、下段腫瘤患者頸淋巴結(jié)轉(zhuǎn)移率依次為33.4%、22.8%和17.6%，術(shù)后5年生存率分別為42.3%、40.5%和30%，他們最后認(rèn)為食管上段鱗癌患者必須行頸淋巴結(jié)清掃，對(duì)于中段患者也推薦行3-FL。此外，也有少數(shù)研究報(bào)道對(duì)于食管胸下段鱗癌伴中上縱隔淋巴結(jié)轉(zhuǎn)移患者，甚至對(duì)于腫瘤侵及粘膜下層(T1b期)和淋巴結(jié)陰性患者也應(yīng)選擇3-FL[21,33-34]。目前對(duì)于胸上段食管鱗癌患者常規(guī)行頸淋巴結(jié)清掃術(shù)已為大多數(shù)學(xué)者所接受，對(duì)中下段患者術(shù)前伴頸淋巴結(jié)轉(zhuǎn)移患者也應(yīng)選擇3-FL，但對(duì)于術(shù)前常規(guī)檢查頸淋巴結(jié)陰性的食管中下段鱗癌患者，是否有必要行預(yù)防性頸淋巴結(jié)清掃術(shù)仍存在爭(zhēng)議。

2 食管癌頸淋巴結(jié)轉(zhuǎn)移診斷現(xiàn)狀

食管癌患者頸部淋巴結(jié)是否存在轉(zhuǎn)移直接決定術(shù)中淋巴結(jié)清掃術(shù)式。因此，術(shù)前準(zhǔn)確評(píng)價(jià)頸淋巴結(jié)有無(wú)轉(zhuǎn)移至關(guān)重要[7]。由于術(shù)前查體診斷準(zhǔn)確率低，多種無(wú)創(chuàng)檢查方法(如超聲、MRI、CT、PET-CT)和有創(chuàng)檢查方法(如EUS和EUS-FNA)已被廣泛用于術(shù)前診斷食管癌頸淋巴結(jié)良惡性[8,35]。但是綜合考慮準(zhǔn)確性、方便性、經(jīng)濟(jì)性及安全性等因素，超聲目前仍是術(shù)前篩選食管癌頸淋巴結(jié)轉(zhuǎn)移的首選無(wú)創(chuàng)檢查。

2.1 超聲

超聲學(xué)上淋巴結(jié)轉(zhuǎn)移的診斷依據(jù)主要參考淋巴結(jié)大小、邊界及內(nèi)部回聲、內(nèi)部血流分布和淋巴門(mén)表現(xiàn)等[36]。目前超聲診斷食管癌頸淋巴結(jié)轉(zhuǎn)移主要依據(jù)淋巴結(jié)大小和邊界及內(nèi)部回聲。Yoshinaka等[37]根據(jù)邊界及內(nèi)部回聲表現(xiàn)，將食管癌頸淋巴結(jié)分為3種類型，第1型：邊界回聲不清，內(nèi)部回聲均勻；第2型：邊界回聲清，內(nèi)部弱回聲；第3型：邊界回聲清楚，邊緣不光滑，內(nèi)部回聲不均勻，一般認(rèn)為第2、3型惡性可能性大，尤其第3型診斷敏感性、特異性和準(zhǔn)確性分別高達(dá)92.3%、96.3%和95.7%。Natsugoe等[38]報(bào)道該標(biāo)準(zhǔn)的敏感性、特異性及準(zhǔn)確性分別為74.5%、94.1% 和87.6%。然而，淋巴結(jié)邊界及內(nèi)部回聲判斷主觀性強(qiáng)，與檢查者經(jīng)驗(yàn)明顯相關(guān)，因此，根據(jù)淋巴結(jié)大小選擇量化指標(biāo)更為可靠。超聲下淋巴結(jié)直徑及長(zhǎng)短徑之比已被廣泛作為鑒別良惡性標(biāo)準(zhǔn)，但是缺乏統(tǒng)一的陽(yáng)性分界值。Tohnosu等[9]早期報(bào)道了58例胸段食管癌患者經(jīng)超聲診斷頸淋巴結(jié)轉(zhuǎn)移情況，當(dāng)淋巴結(jié)陽(yáng)性分界值定為超聲測(cè)量長(zhǎng)徑大于1cm且短徑/長(zhǎng)徑大于0.5時(shí)，診斷敏感性、特異性及準(zhǔn)確率分別為78.4%、93.3% 和90.4%。Tachimori等[10]分析了209例胸段食管癌患者術(shù)前頸淋巴結(jié)轉(zhuǎn)移情況，包括鱗癌192例，結(jié)果顯示超聲測(cè)量下陽(yáng)性淋巴結(jié)的分界值定為短徑≥5mm且短徑/長(zhǎng)徑≥0.5時(shí)，診斷敏感性及準(zhǔn)確性分別為78.9% 和94.0%。Leng等[7]最近發(fā)表的meta分析評(píng)價(jià)了超聲診斷食管癌頸淋巴結(jié)轉(zhuǎn)移的情況，納入了22項(xiàng)研究共計(jì)3 513例食管癌患者，分析結(jié)果顯示當(dāng)超聲測(cè)量下陽(yáng)性頸淋巴結(jié)大小分界值為5mm及>5mm時(shí)，敏感性分別為84% (67%～93%) 與93% (90%～95%)，特異性分別為94% (76%～98%) 與 98% (89%～100%)。但由于超聲測(cè)量食管癌患者直徑小于5mm的淋巴結(jié)中，病理診斷陽(yáng)性率高達(dá)36%～42%[39]，因此，單獨(dú)將超聲下淋巴結(jié)大小或邊界及內(nèi)部回聲表現(xiàn)作為陽(yáng)性標(biāo)準(zhǔn)并不是最佳選擇，應(yīng)該綜合淋巴結(jié)大小和形態(tài)學(xué)表現(xiàn)建立最佳診斷標(biāo)準(zhǔn)。日本食管疾病協(xié)會(huì)推薦的超聲下陽(yáng)性淋巴結(jié)標(biāo)準(zhǔn)為：1.邊界清楚；2.內(nèi)部回聲不均勻；3.短徑/長(zhǎng)徑大于0.5；4.長(zhǎng)徑大于5mm，同時(shí)滿足以上標(biāo)準(zhǔn)時(shí)，診斷敏感性、特異性、準(zhǔn)確率、假陽(yáng)性率和假陰性率分別為71.4%、100%、87.7%、10.5%和0%[40]。Cwik 等[41]近期報(bào)道了超聲診斷83例食管胸段鱗癌患者頸淋巴結(jié)轉(zhuǎn)移的情況，根據(jù)上述標(biāo)準(zhǔn)，超聲診斷的敏感性、特異性、陽(yáng)性及陰性預(yù)測(cè)值分別為100%、96%、81% 和100%?？傮w來(lái)看，雖然超聲診斷頸淋巴結(jié)轉(zhuǎn)移的準(zhǔn)確性較高，但是與檢查者經(jīng)驗(yàn)、檢查設(shè)備等因素密切相關(guān)，目前缺乏統(tǒng)一標(biāo)準(zhǔn)。盡管多普勒頻譜分析技術(shù)(Doppler spectral analysis)和超聲彈性成像技術(shù)(elastography)等檢查方法也被用于診斷頸淋巴結(jié)轉(zhuǎn)移，但仍處在研究初期[42-43]。

2.2 MRI和PET/MR

常規(guī)MRI診斷淋巴結(jié)轉(zhuǎn)移的敏感性、特異性及準(zhǔn)確性分別為25%～62 %, 67%～88 % 和56%～77 %[44]。PET/MR是一種在MRI和PET基礎(chǔ)上發(fā)展起來(lái)的新興檢測(cè)技術(shù)，診斷食管癌淋巴結(jié)轉(zhuǎn)移的準(zhǔn)確性為83.3%[45]。綜上可見(jiàn)，MRI和PET/MR診斷準(zhǔn)確性并未較其他無(wú)創(chuàng)檢查明顯提高，尤其是PET/MR費(fèi)用昂貴，目前較少用于術(shù)前診斷食管癌淋巴結(jié)轉(zhuǎn)移。雖然隨著高分辨率MRI、超順磁性氧化鐵(SPIO)MRI及彌散加權(quán)成像技術(shù)等新技術(shù)的出現(xiàn)，MRI診斷食管癌淋巴結(jié)轉(zhuǎn)移敏感性可達(dá)81%～100%，特異性達(dá)90%以上[46-48]，但目前仍處于臨床研究階段。

2.3 CT和PET/CT

已報(bào)道的CT診斷食管癌頸淋巴結(jié)轉(zhuǎn)移的敏感性為30%～75.9 %，特異性為34.0 %～93%[8,49-51],主要由于CT對(duì)直徑大小正常的轉(zhuǎn)移淋巴結(jié)分辨率低；此外，炎癥及結(jié)核等原因引起的腫大淋巴結(jié)均導(dǎo)致CT診斷的假陽(yáng)性率增加[52]。目前PET/CT診斷食管癌淋巴結(jié)轉(zhuǎn)移的敏感性為49%～57%，特異性為81.1 %～87%[8,50-51]。可見(jiàn)PET/CT診斷準(zhǔn)確性并未較CT明顯提高，分析可能原因?yàn)椋?1)PET/CT空間分辨率低，對(duì)于轉(zhuǎn)移的小淋巴結(jié)診斷能力有限[53-54]；(2)原發(fā)腫瘤對(duì)FDG吸收與腫瘤周圍淋巴結(jié)對(duì)FDG的吸收相互影響PET/CT的準(zhǔn)確鑒別[55]；(3)僅有鏡下轉(zhuǎn)移的淋巴結(jié)對(duì)FDG吸收少且體積無(wú)明顯長(zhǎng)大， PET-CT對(duì)其診斷準(zhǔn)確率低[56]。綜上可知，CT診斷食管癌頸淋巴結(jié)轉(zhuǎn)移準(zhǔn)確性低，PET/CT雖然對(duì)于診斷原發(fā)腫瘤及遠(yuǎn)處轉(zhuǎn)移有較高準(zhǔn)確性，但鑒別淋巴結(jié)轉(zhuǎn)移良惡性的敏感性及特異性較低。

2.4 EUS和EUS-FNA

EUS作為一種有創(chuàng)檢查手段，其診斷食管癌淋巴結(jié)轉(zhuǎn)移的敏感性為42%～100%，特異性為70%～91%[8,48,50,57]。尤其隨著高分辨率內(nèi)鏡的出現(xiàn)，EUS診斷淋巴結(jié)轉(zhuǎn)移準(zhǔn)確率明顯提高[57]。術(shù)前在EUS引導(dǎo)基礎(chǔ)上對(duì)發(fā)現(xiàn)的可疑淋巴結(jié)行細(xì)針穿刺活檢，可以進(jìn)一步提高EUS診斷準(zhǔn)確率。目前報(bào)道的EUS-FNA診斷食管癌淋巴結(jié)轉(zhuǎn)移的敏感性、特異性及準(zhǔn)確性分別達(dá)93%、100%和98%[54,58-59]。盡管EUS和EUS-FNA對(duì)于術(shù)前鑒別食管癌淋巴結(jié)良惡性十分有用，但兩者作為有創(chuàng)操作，對(duì)術(shù)者能力要求高，并有穿孔風(fēng)險(xiǎn)。此外，EUS穿透深度約為5cm，兩者主要用于診斷食管腫瘤周圍的較大可疑淋巴結(jié)，對(duì)于遠(yuǎn)處轉(zhuǎn)移淋巴結(jié)診斷能力低[54,60]?？紤]到有創(chuàng)性及使用范圍有限等特點(diǎn)，EUS和EUS-FNA雖然診斷準(zhǔn)確性高，但并不是術(shù)前鑒別食管癌頸淋巴結(jié)良惡性的首選方法。

3 食管癌前哨淋巴結(jié)研究現(xiàn)狀

食管胸段鱗癌患者術(shù)前有無(wú)頸部淋巴結(jié)轉(zhuǎn)移直接決定是否行頸淋巴結(jié)清掃。上述各種檢查方法雖然對(duì)較大淋巴結(jié)診斷準(zhǔn)確性較高，但對(duì)較小轉(zhuǎn)移淋巴結(jié)，尤其是僅有微轉(zhuǎn)移灶的淋巴結(jié)診斷準(zhǔn)確率低。由于解剖學(xué)上縱隔喉返神經(jīng)旁淋巴結(jié)處于頸胸交界區(qū)，是胸內(nèi)最高淋巴結(jié)，并通過(guò)淋巴導(dǎo)管與頸淋巴結(jié)直接交通[61]；此外，食管癌患者喉返神經(jīng)旁淋巴結(jié)轉(zhuǎn)移率最高，與預(yù)后密切相關(guān)[29,62]。因此，一些學(xué)者嘗試將喉返神經(jīng)旁淋巴結(jié)作為食管癌的“前哨淋巴結(jié)”預(yù)測(cè)頸淋巴結(jié)有無(wú)轉(zhuǎn)移，進(jìn)而指導(dǎo)是否需要行頸淋巴結(jié)清掃[11-13,19,63]。Tabira等[12]早期報(bào)道了86例食管胸段鱗癌患者R0切除術(shù)后喉返神經(jīng)旁淋巴結(jié)轉(zhuǎn)移情況，喉返神經(jīng)旁淋巴結(jié)陽(yáng)性與陰性患者頸淋巴結(jié)轉(zhuǎn)移率分別為43.5%(10/23)，和11.1%(7/63)(P=0.001)，喉返神經(jīng)旁淋巴結(jié)預(yù)測(cè)頸淋巴結(jié)轉(zhuǎn)移的敏感性、特異性、陽(yáng)性預(yù)測(cè)值及陰性預(yù)測(cè)值分別為58.8%、81.2%、43.5%和88.8%，多變量分析顯示喉返神經(jīng)旁淋巴結(jié)轉(zhuǎn)移與頸淋巴結(jié)轉(zhuǎn)移明顯相關(guān)(OR=4.5,95%CI=1.3～15.9,P=0.02)。Ueda等[13]后期分析了71例胸段食管癌患者喉返神經(jīng)旁淋巴結(jié)與頸淋巴結(jié)轉(zhuǎn)移的情況，喉返神經(jīng)旁淋巴結(jié)陽(yáng)性與陰性患者頸淋巴結(jié)總轉(zhuǎn)移率分別為40.9%和10.2%(P=0.007)，多變量logistic回歸分析顯示喉返神經(jīng)旁淋巴結(jié)轉(zhuǎn)移與中下段食管癌患者頸淋巴結(jié)轉(zhuǎn)移明顯相關(guān)(P=0.03)。作者進(jìn)一步比較了41例術(shù)中根據(jù)喉返神經(jīng)旁淋巴結(jié)冰凍結(jié)果決定是否選擇頸淋巴結(jié)清掃患者的預(yù)后情況，當(dāng)喉返神經(jīng)旁淋巴結(jié)冰凍結(jié)果為陽(yáng)性時(shí)選擇頸淋巴結(jié)清掃，陰性時(shí)放棄頸淋巴結(jié)清掃，10例因?yàn)樾g(shù)中喉返神經(jīng)旁淋巴結(jié)冰凍陽(yáng)性而接受了頸淋巴結(jié)清掃的患者中2例患者經(jīng)術(shù)后病理證實(shí)存在頸淋巴結(jié)轉(zhuǎn)移。隨訪結(jié)果顯示術(shù)中根據(jù)喉返神經(jīng)旁淋巴結(jié)冰凍結(jié)果選擇性頸清組患者與常規(guī)頸清組患者術(shù)后頸淋巴結(jié)復(fù)發(fā)率分別2.6%(1/39)和6.7%(2/30)(P=0.5757)，3年生存率分別為83.3%和57.2%(P<0.05)。Taniyama等[11]和Li等[19]近期研究也顯示縱隔內(nèi)喉返神經(jīng)旁淋巴結(jié)可以作為食管癌頸淋巴結(jié)有無(wú)轉(zhuǎn)移的預(yù)測(cè)因子。綜上分析，喉返神經(jīng)旁淋巴結(jié)雖然在一定程度上可以預(yù)測(cè)頸淋巴結(jié)轉(zhuǎn)移，但準(zhǔn)確率較低。此外，上述均為小樣本回顧性研究，證據(jù)級(jí)別低。因此，喉返神經(jīng)旁淋巴結(jié)能否作為食管癌的前哨淋巴結(jié)仍需進(jìn)一步研究證實(shí)。

4 結(jié) 語(yǔ)

總之，目前對(duì)于上段食管癌及頸部淋巴結(jié)陽(yáng)性患者，三野淋巴結(jié)清掃的優(yōu)勢(shì)已經(jīng)逐漸得到認(rèn)同,但是術(shù)后并發(fā)癥高，因此，對(duì)于中下段腫瘤及頸淋巴結(jié)陰性患者是否該預(yù)防性頸淋巴結(jié)清掃目前存在爭(zhēng)議。作者認(rèn)為應(yīng)該結(jié)合頸部超聲及腫瘤位置，同時(shí)根據(jù)患者自身各方面特點(diǎn)選擇精準(zhǔn)化頸淋巴結(jié)清掃。術(shù)前頸部淋巴結(jié)轉(zhuǎn)移的診斷手段雖然眾多，鑒于安全經(jīng)濟(jì)及高敏感性和特異性等優(yōu)點(diǎn)，頸部超聲仍然是首選方法，綜合淋巴結(jié)大小和形態(tài)學(xué)表現(xiàn)建立陽(yáng)性診斷標(biāo)準(zhǔn)是較為合理的選擇。關(guān)于前哨淋巴結(jié)的問(wèn)題，從目前文獻(xiàn)來(lái)看，喉返神經(jīng)旁淋巴結(jié)與頸淋巴結(jié)陽(yáng)性及陰性一致率都不高。此外，食管癌的淋巴引流系統(tǒng)非常復(fù)雜，存在“跳躍轉(zhuǎn)移”特性，常規(guī)的檢測(cè)方法對(duì)于淋巴結(jié)轉(zhuǎn)移，尤其是對(duì)微轉(zhuǎn)移的診斷準(zhǔn)確率低。因此，喉返神經(jīng)旁淋巴結(jié)能否作為食管癌的前哨淋巴結(jié)仍然存在較大爭(zhēng)議。以上問(wèn)題有待于進(jìn)一步前瞻性大樣本隨機(jī)對(duì)照研究來(lái)解決。

作者聲明：本文第一作者對(duì)于研究和撰寫(xiě)的論文出現(xiàn)的不端行為承擔(dān)相應(yīng)責(zé)任；

利益沖突：本文全部作者均認(rèn)同文章無(wú)相關(guān)利益沖突；

學(xué)術(shù)不端：本文在初審、返修及出版前均通過(guò)中國(guó)知網(wǎng)(CNKI)科技期刊學(xué)術(shù)不端文獻(xiàn)檢測(cè)系統(tǒng)學(xué)術(shù)不端檢測(cè)；

同行評(píng)議：經(jīng)同行專家雙盲外審，達(dá)到刊發(fā)要求。

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ResearchAdvancesintheDiagnosisandTreatmentoftheCervicalLymphNodeMetastasisofEsophagealCancer*

Wang Haijun1, Han Yongtao1,2△

(1.TheSouthwestMedicalUniversity,Luzhou646000,Sichuan,China; 2.TheDepartmentofThoracicSurgery,SichuanCancerHospital&Intitute,SichuanCancerCenter,SchoolofMedicine,UniversityofElectronicScienceandTechnologyofChina,Chengdu610041,Sichuan,China)

Esophageal cancer is a highly malignant tumor with a poor prognosis. Lymph node involvement and the number of positive nodes , especially the cervical and recurrent laryngeal nerve nodes, are independent prognostic predictors after esophagectomy . Three-field lymphadenectomy (3-FL) may prevent recurrence and prolong survival for esophagus carcinoma when compared with two-field lymphadenectomy (2-FL),whereas it is also a highly invasive procedure that can lead to severe complications .The status of cervical lymph nodes is one of the most important factors to identify whether 3-FL should be performed. Unfortunately,current clinically used approaches demonstrated a lower sensitivity and specificity in identifying cervical lymph node metastasis. Recurrent laryngeal nerve nodes also have been regarded as the sentinel nodes to predict cervical node metastasis with an accuracy of less than 50% . We will review the current diagnosis and treatment progress of cervical lymph node metastasis of esophageal cancer.

Esophageal Cancer； Lymphadenectomy； Cervical Lymph Node; Ultrasonography； Sentinel Node

2017- 02- 24 [

] 2017- 04- 06

*國(guó)家科技支撐計(jì)劃項(xiàng)目(編號(hào)：2015BAI12B08)

△韓泳濤，E-mail:hanyongt@aliyun.com

R735.1；R730.41；R730.56

A

10.3969/j.issn.1674- 0904.2017.03.013

Wang HJ, Han YT.Research advances in the diagnosis and treatment of the cervical lymph node metastasis of esophageal cancer [J].J Cancer Control Treat, 2017,30(3):219-225.[王海軍, 韓泳濤.胸段食管鱗癌頸淋巴轉(zhuǎn)移診治進(jìn)展 [J].腫瘤預(yù)防與治療，2017,30(3):219-225.]