程芳芳 張紅燕 夏婷 孟靈

內(nèi)鏡超聲引導(dǎo)下細(xì)針穿刺如何獲取高質(zhì)量的樣本

程芳芳 張紅燕 夏婷 孟靈

內(nèi)鏡超聲引導(dǎo)下細(xì)針穿刺抽吸術(shù)(endoscopic ultrasonography guided fine needle aspiration, EUS-FNA)是臨床上獲取胃腸道及其鄰近器官病變和淋巴結(jié)組織樣本用于病理學(xué)診斷的首選方法[1]。在其他常規(guī)影像學(xué)檢查發(fā)現(xiàn)病變后，臨床上通常采用EUS-FNA獲取目標(biāo)細(xì)胞或組織行最終的病理診斷。目前文獻(xiàn)所報(bào)道的EUS-FNA的診斷準(zhǔn)確率為65%～96%[2]。多種因素如病變的位置、大小，現(xiàn)場(chǎng)是否有病理醫(yī)師及操作醫(yī)師的個(gè)人經(jīng)驗(yàn)均可影響EUS-FNA的準(zhǔn)確性[3]。然而，目前對(duì)于能夠獲得最大準(zhǔn)確性和最少穿刺針數(shù)的最佳EUS-FNA穿刺技術(shù)仍然存在爭(zhēng)議。本文就EUS-FNA如何獲取高質(zhì)量樣本的相關(guān)技術(shù)進(jìn)行探討。

一、穿刺針

1．常規(guī)穿刺針：目前臨床上使用的穿刺針有19G、22G、25G 3種不同型號(hào)。在實(shí)際臨床工作中，需要根據(jù)不同情況，如是否能夠獲得最終診斷、能否易于到達(dá)病變部位、并發(fā)癥是否最低等因素選擇合適大小的穿刺針。目前認(rèn)為不同的穿刺針對(duì)EUS-FNA的樣本獲取的質(zhì)量影響不大[4-10]，但最新一項(xiàng)涉及144例患者的前瞻性隨機(jī)對(duì)照研究顯示，對(duì)實(shí)性腫瘤采用25G針穿刺樣本準(zhǔn)確性高達(dá)95.8%，優(yōu)于22G穿刺針[11]，因此穿刺針型號(hào)的選擇仍需進(jìn)一步的研究。

2．組織針(ProCore)：ProCore針是新近出現(xiàn)的以達(dá)到組織活檢為目的的在EUS引導(dǎo)下穿刺的穿刺針。ProCore主要特點(diǎn)是在穿刺針的前端存在一個(gè)反向斜面。目前有多篇文獻(xiàn)評(píng)價(jià)了EUS引導(dǎo)下ProCore針穿刺的可行性及安全性[12-13]。最近一項(xiàng)Meta分析對(duì)ProCore針和常規(guī)穿刺針的差異進(jìn)行了探討[14]。該項(xiàng)Meta分析納入9項(xiàng)研究共578例患者，結(jié)果發(fā)現(xiàn)樣本的充足性、診斷準(zhǔn)確性及核心樣本率差異并無(wú)統(tǒng)計(jì)學(xué)意義，但ProCore針獲得診斷所需要的針道數(shù)要低于常規(guī)穿刺針。

二、EUS-FNA的穿刺技術(shù)

1．負(fù)壓吸引：負(fù)壓吸引在EUS-FNA穿刺過(guò)程中的作用仍然不明確。有文獻(xiàn)認(rèn)為持續(xù)的低負(fù)壓吸引能夠獲得較好的細(xì)胞量和樣本質(zhì)量[15]。2006年的一項(xiàng)Meta分析認(rèn)為負(fù)壓吸引并不能提高EUS-FNA的穿刺樣本質(zhì)量[16]。2009年P(guān)uri等[17]做的一項(xiàng)前瞻性隨機(jī)對(duì)照試驗(yàn)評(píng)價(jià)10 ml負(fù)壓和無(wú)負(fù)壓吸引對(duì)最終穿刺樣本量的影響。該研究共納入了52例患者，研究結(jié)果顯示，與無(wú)負(fù)壓組相比，10 ml負(fù)壓能夠得到較多的樣本量，且不會(huì)增加樣本的血污染程度。另外，負(fù)壓組的穿刺樣本的診斷敏感性和陰性預(yù)測(cè)值均高于無(wú)負(fù)壓組。最新的一項(xiàng)前瞻性研究采用22G或25G針對(duì)85例患者分別采用10 ml負(fù)壓和無(wú)負(fù)壓進(jìn)行穿刺，結(jié)果顯示，10 ml負(fù)壓穿刺的準(zhǔn)確性和敏感性均高于無(wú)負(fù)壓組，但10 ml負(fù)壓組樣本的血污染程度要高于無(wú)負(fù)壓組[18]。Kudo等[19]使用25G穿刺針對(duì)34例患者分別采用10 ml和50 ml負(fù)壓穿刺，發(fā)現(xiàn)與低負(fù)壓相比，高負(fù)壓能獲得更多的樣本，但該研究未評(píng)價(jià)兩者獲取樣本的血污染情況。

2．慢提拉法(slow-pull)：是指穿刺針在病變組織中反復(fù)提插穿刺時(shí)緩慢地抽出穿刺針針芯，在穿刺針中行成微負(fù)壓的穿刺方法，以達(dá)到增加樣本量和減少樣本血污染的目的。Nakai等[20]對(duì)93例胰腺實(shí)性占位病變分別采用slow-pull法和負(fù)壓吸引(10 ml或20 ml)穿刺，發(fā)現(xiàn)用25G針穿刺時(shí)與負(fù)壓吸引相比，slow-pull法雖然得到的穿刺樣本細(xì)胞量較少，但其最終診斷準(zhǔn)確性高(90.0%比67.9%)，且樣本血污染程度較輕。但用22G針中穿刺的兩組差異無(wú)統(tǒng)計(jì)學(xué)意義。Kin等[21]研究發(fā)現(xiàn)，22G穿刺針采用slow-pull法穿刺能夠獲得充足的質(zhì)量較高且血污染較少的樣本，但slow-pull法與20 ml負(fù)壓最終診斷準(zhǔn)確性相同。

3．有無(wú)針芯：穿刺針中的針芯是為了防止穿刺針在進(jìn)入病變組織之前混入胃腸道的組織，影響最終診斷的準(zhǔn)確性。然而針芯的存在會(huì)增加勞動(dòng)成本、延長(zhǎng)手術(shù)時(shí)間和增加鎮(zhèn)靜藥物的劑量。Sahai等[22]在2010年進(jìn)行了一項(xiàng)前瞻性對(duì)照試驗(yàn)，對(duì)135個(gè)病變分別采用有針芯和無(wú)針芯針進(jìn)行了309次穿刺，有針芯針獲得的樣本含量較少，且血污染情況較重，因此認(rèn)為有針芯的針穿刺不能提高診斷的準(zhǔn)確性。一項(xiàng)涉及3078例患者的大樣本研究及最新一項(xiàng)多中心隨機(jī)對(duì)照試驗(yàn)則認(rèn)為有無(wú)針芯對(duì)EUS-FNA穿刺的樣本含量、血污染情況無(wú)影響[23-24]。

4．扇形穿刺：是指在EUS-FNA穿刺過(guò)程中，穿刺針從病變左邊呈扇形向右邊穿刺，直到到達(dá)病變右邊邊緣。與傳統(tǒng)的中心區(qū)域穿刺相比，扇形穿刺針道的準(zhǔn)確性高且樣本血污染較輕。Bang等[25]設(shè)計(jì)了一項(xiàng)隨機(jī)對(duì)照試驗(yàn)比較扇形穿刺法和標(biāo)準(zhǔn)穿刺法獲取樣本的差異。該試驗(yàn)納入54例患者，其中26例采用標(biāo)準(zhǔn)穿刺法，28例采用扇形穿刺法，兩者診斷準(zhǔn)確性和并發(fā)癥差異無(wú)統(tǒng)計(jì)學(xué)意義。但是與標(biāo)準(zhǔn)穿刺法相比，扇形穿刺法獲得的樣本達(dá)到診斷目的所需的穿刺針數(shù)較少。

5．濕抽法(wet-suction)：是指在穿刺靶向病變之前移除針芯，在穿刺針內(nèi)注以5 ml無(wú)菌生理鹽水，然后注入3 ml無(wú)菌生理鹽水用的10 ml注射器中，接到穿刺針的近端，負(fù)壓吸引病變。Attam等[26]設(shè)計(jì)了一項(xiàng)前瞻性單盲隨機(jī)對(duì)照試驗(yàn)評(píng)價(jià)濕抽法穿刺與常規(guī)穿刺法獲取樣本質(zhì)量的差異。該研究發(fā)現(xiàn)與常規(guī)穿刺法相比，濕抽法能獲得較多的樣本量，而血污染情況無(wú)差異。但該研究未對(duì)兩者不同的穿刺方法最終的診斷準(zhǔn)確性進(jìn)行比較。

三、現(xiàn)場(chǎng)病理評(píng)估的影響

獲得足夠的樣本是建立準(zhǔn)確診斷的前提?？焖佻F(xiàn)場(chǎng)病理亦評(píng)估(rapid on-site evaluation, ROSE)的作用在于現(xiàn)場(chǎng)給穿刺樣本實(shí)時(shí)反饋，以達(dá)到提高最終診斷的準(zhǔn)確性、減少穿刺針道數(shù)的目的。然而，目前ROSE的臨床作用仍然存在爭(zhēng)議。兩篇Meta分析結(jié)果認(rèn)為，ROSE的應(yīng)用能夠顯著提高穿刺樣本量[27-28]。但Matynia等[27]的研究認(rèn)為ROSE需要更多的針道數(shù)，而Schmidt等[28]的研究則發(fā)現(xiàn)ROSE并不能提高EUS-FNA的檢出率。最新的一項(xiàng)前瞻性隨機(jī)對(duì)照試驗(yàn)顯示，ROSE除了可以降低穿刺針道數(shù)以外，并不能提高穿刺樣本的充足性及最終診斷的準(zhǔn)確性[29]，并且有無(wú)ROSE穿刺所需的操作時(shí)間、并發(fā)癥、需要重復(fù)穿刺率及最終費(fèi)用也無(wú)差異。

另外，由于人員及資金條件受限，多數(shù)醫(yī)療單位也無(wú)法實(shí)現(xiàn)ROSE。為此，Iwashita等[30]最近對(duì)宏觀現(xiàn)場(chǎng)評(píng)價(jià)(macroscopic on-site evaluation, MOSE)的作用進(jìn)行了探討。研究對(duì)111例病變采用19G穿刺針進(jìn)行EUS-FNA穿刺。MOSE顯示91.1%的例數(shù)存在宏觀可見(jiàn)核心樣本(macroscopic visible core, MVC)，中位長(zhǎng)度為8 mm。ROC曲線顯示診斷的臨界值為4 mm，曲線下面積達(dá)0.893。研究者認(rèn)為以4 mm作為臨界值可作為樣本充足性判斷從而提高EUS-FNA的診斷收益。因此在ROSE沒(méi)有條件實(shí)現(xiàn)的情況下，MOSE亦能夠獲得樣本進(jìn)行質(zhì)量評(píng)價(jià)，以達(dá)到提高診斷準(zhǔn)確性的目的。

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(本文編輯：屠振興)

10.3760/cma.j.issn.1674-1935.2017.04.021

200433 上海，第二軍醫(yī)大學(xué)長(zhǎng)海醫(yī)院消化內(nèi)科

張紅燕，Email:13601609798@163.com

2016-06-23)