劉學(xué)臣 姜慧卿

·專家論壇·

內(nèi)鏡技術(shù)預(yù)防ERCP術(shù)后胰腺炎

劉學(xué)臣 姜慧卿

(姜慧卿，醫(yī)學(xué)博士、河北醫(yī)科大學(xué)第二醫(yī)院消化科主任、教授、主任醫(yī)師、博士生導(dǎo)師。河北省消化病研究所所長(zhǎng)，河北省消化病重點(diǎn)實(shí)驗(yàn)室主任。享受國(guó)務(wù)院政府特貼，中華醫(yī)學(xué)會(huì)消化內(nèi)鏡學(xué)會(huì)常委，中國(guó)醫(yī)師協(xié)會(huì)內(nèi)鏡醫(yī)師分會(huì)常委，中國(guó)醫(yī)師協(xié)會(huì)消化病學(xué)分會(huì)委員，河北省醫(yī)學(xué)會(huì)消化內(nèi)鏡學(xué)分會(huì)主委，河北省醫(yī)學(xué)會(huì)消化病學(xué)分會(huì)侯任主任委員。主要研究方向?yàn)槁愿尾?、消化系疾病?nèi)鏡介入診治。承擔(dān)省自然基金、國(guó)家自然基金和科技廳等課題8項(xiàng)。獲省部級(jí)獎(jiǎng)勵(lì)5項(xiàng)，其中河北省科技進(jìn)步一等獎(jiǎng)1項(xiàng)；發(fā)表醫(yī)學(xué)論文150余篇，其中SCI收錄論文20篇；主編參編教材和醫(yī)學(xué)專著15部。)

內(nèi)鏡下逆行胰膽管造影(endoscopic retrograde cholangiopancreatography, ERCP)術(shù)后胰腺炎(post-ERCP pancreatitis，PEP)是ERCP最常見(jiàn)的并發(fā)癥，發(fā)生率為3.5%，其中90%為輕、中度，但仍然有嚴(yán)重病例導(dǎo)致死亡。PEP的發(fā)生機(jī)制尚未完全明確，一般認(rèn)為多因素參與，包括機(jī)械性損傷(乳頭插管、胰管導(dǎo)絲置入、乳頭括約肌切開(kāi)等)、化學(xué)性損傷(胰管造影)、靜水壓力性損傷(灌注式Oddi括約肌測(cè)壓)和感染。其中，幾乎每個(gè)方面均與ERCP操作技術(shù)相關(guān)。

一、PEP定義

1991年Cotton等[1]將PEP定義為ERCP術(shù)后出現(xiàn)急性胰腺炎相關(guān)的臨床癥狀持續(xù)超過(guò)24 h，同時(shí)伴有血清淀粉酶超過(guò)正常參考值上限3倍以上。按PEP的嚴(yán)重程度又分為輕度PEP：(有)臨床(癥狀的)胰腺炎，ERCP術(shù)后24 h血清淀粉酶超過(guò)正常體重上限的3倍，需要住院或住院時(shí)間延遲2～3 d；中度PEP：住院時(shí)間為4～10 d；重度PEP：住院時(shí)間>10 d，并發(fā)出血性胰腺炎，胰腺壞死或假性囊腫，或需要經(jīng)皮穿刺引流或外科手術(shù)。

2012年Atlanta定義PEP的臨床診斷只需滿足以下3個(gè)指標(biāo)中的任意兩項(xiàng)：持續(xù)性腹痛；血清淀粉酶或脂肪酶較正常參考值上限增高3倍以上；CT、MRI或腹部B超可見(jiàn)胰腺炎特征表現(xiàn)。但該標(biāo)準(zhǔn)并非針對(duì)PEP制定，在臨床研究中仍未得到廣泛采納。

二、發(fā)生PEP的危險(xiǎn)因素

2014年歐洲消化內(nèi)鏡學(xué)會(huì)將發(fā)生PEP的危險(xiǎn)因素劃分為患者及操作相關(guān)兩方面。確定的患者相關(guān)危險(xiǎn)因素有女性、Oddi括約肌功能障礙(SOD)和既往胰腺炎病史；可能的危險(xiǎn)因素有既往PEP、年輕、無(wú)肝外膽管擴(kuò)張、無(wú)慢性胰腺炎和血清膽紅素正常。確定的操作相關(guān)危險(xiǎn)因素有嘗試插管困難；可能的危險(xiǎn)因素有預(yù)切開(kāi)括約肌、胰管括約肌切開(kāi)、膽道球囊擴(kuò)張、清理膽管結(jié)石失敗和管內(nèi)超聲。但因研究者的主觀性明顯，各個(gè)研究對(duì)“困難插管”界定的范疇卻很不統(tǒng)一。2016年歐洲消化內(nèi)鏡學(xué)會(huì)在ERCP乳頭插管和括約肌切開(kāi)術(shù)的臨床指南中將其定義為接觸乳頭的插管>5次；在乳頭直視下插管時(shí)間>5 min；非目的性胰管插管或胰管造影>1次。

三、預(yù)防PEP的內(nèi)鏡技術(shù)

1．改進(jìn)插管技術(shù)，減少插管次數(shù)：10～14次插管嘗試能夠使PEP發(fā)生率增長(zhǎng)到11.5%，15次插管嘗試則可進(jìn)一步增長(zhǎng)至15%[2]。插管持續(xù)時(shí)間>10 min是PEP獨(dú)立風(fēng)險(xiǎn)因素，PEP發(fā)生率從3.8%增加到10.8%[3]。改進(jìn)插管技術(shù)、提高插管成功率及減少插管時(shí)間、次數(shù)有利于降低PEP風(fēng)險(xiǎn)，因此規(guī)范化培訓(xùn)至關(guān)重要。

2．導(dǎo)絲輔助插管：歐美的研究結(jié)果顯示，單導(dǎo)絲引導(dǎo)插管較造影劑輔助插管提高了插管成功率，并降低了PEP風(fēng)險(xiǎn)，推薦該技術(shù)應(yīng)用于初次膽道插管[4-5]。但日本的RCT研究結(jié)果顯示，兩者在膽管插管成功率和PEP發(fā)生率方面差異無(wú)統(tǒng)計(jì)學(xué)意義[6-8]。其原因可能是西方多采用5度后仰角的十二指腸鏡，而日本則應(yīng)用15度后仰角的內(nèi)鏡，后者更容易擺放或調(diào)整十二指腸鏡角度以適應(yīng)膽總管軸向。此外，為防止導(dǎo)絲非目的性進(jìn)入胰管，插管過(guò)程中應(yīng)注意造影管軸向與膽管軸向一致[9-10]。而應(yīng)用不同導(dǎo)絲直徑(0.025英寸和0.035英寸)、不同導(dǎo)絲前端設(shè)計(jì)(Looptip帶圈導(dǎo)絲和直頭導(dǎo)絲、J型頭端導(dǎo)絲和成角型頭端導(dǎo)絲)引導(dǎo)插管的PEP發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義。

雙導(dǎo)絲引導(dǎo)插管技術(shù)多用于應(yīng)對(duì)困難插管者。有報(bào)道[11]雙導(dǎo)絲引導(dǎo)插管技術(shù)較單導(dǎo)絲技術(shù)在膽管插管成功率和PEP發(fā)生率方面相當(dāng)。也有報(bào)道[12]雙導(dǎo)絲技術(shù)輔助插管不僅不能夠提高困難插管的成功率，而且增加PEP的風(fēng)險(xiǎn)。然而胰管支架置入可以降低這種風(fēng)險(xiǎn)[13]。

3．括約肌預(yù)切開(kāi)技術(shù)：預(yù)切開(kāi)術(shù)分為乳頭預(yù)切開(kāi)術(shù)、針狀刀造瘺術(shù)和胰管括約肌預(yù)切開(kāi)術(shù)。預(yù)切開(kāi)術(shù)雖然提高了膽管插管成功率，但也增加了PEP風(fēng)險(xiǎn)，發(fā)生率達(dá)2.1%～14.9%[14]。但對(duì)于困難插管患者，早期預(yù)切開(kāi)(5～10 min內(nèi))能夠降低PEP風(fēng)險(xiǎn)[15]，且針狀刀造瘺術(shù)在預(yù)防PEP方面更具有優(yōu)勢(shì)[16]。當(dāng)然最好由預(yù)切開(kāi)經(jīng)驗(yàn)豐富的內(nèi)鏡醫(yī)師實(shí)施，以減少并發(fā)癥。

4．胰管支架置入術(shù)：胰管支架置入不僅能夠降低PEP發(fā)生率，而且能夠減少SAP的發(fā)生。2014年歐洲胃腸內(nèi)鏡學(xué)會(huì)制定的指南對(duì)高危險(xiǎn)因素及導(dǎo)絲反復(fù)非目的性進(jìn)入主胰管患者推薦應(yīng)用5Fr塑料支架預(yù)防PEP。較短的胰管支架(≤4 cm)有利于支架在2周內(nèi)自行移出胰管[17]。72 h內(nèi)支架移出胰管則增加了PEP的風(fēng)險(xiǎn)。近期報(bào)道[18]，在PEP發(fā)生后約10 h急診再次行ERCP胰管支架置入能夠快速緩解PEP疼痛、SIRS以及降低血清淀粉酶、脂肪酶水平。值得注意的是，胰管插管本身就是發(fā)生PEP的一個(gè)危險(xiǎn)因素，即便是操作熟練的ERCP醫(yī)師，失敗率仍達(dá)5%～10%，而失敗后患者的PEP發(fā)生率可高達(dá)34.7%[19]。所以，對(duì)于困難插管患者采取預(yù)防性胰管支架置入需要經(jīng)驗(yàn)豐富的內(nèi)鏡醫(yī)師操作，并對(duì)無(wú)禁忌證患者預(yù)防性應(yīng)用吲哚美辛直腸給藥。

5．內(nèi)鏡下乳頭球囊擴(kuò)張術(shù)(endoscopic papillary balloon dilatation, EPBD)：EPBD較括約肌切開(kāi)術(shù)(endoscopic sphincterotomy, EST)能夠降低出血風(fēng)險(xiǎn)，但PEP發(fā)生率增高，其原因包括球囊擴(kuò)張的壓迫損傷、后續(xù)網(wǎng)籃取石、碎石操作對(duì)乳頭機(jī)械性損傷等。行EPBD患者的插管時(shí)間、取石時(shí)間與PEP呈正相關(guān)[20]。EPBD持續(xù)時(shí)間較長(zhǎng)(>1 min)可降低出血及總體并發(fā)癥的發(fā)生率，且未增加PEP風(fēng)險(xiǎn)，而EPBD持續(xù)時(shí)間較短(≤1 min)則增加了PEP的風(fēng)險(xiǎn)[21]，而在EST后的EPBD持續(xù)時(shí)間對(duì)PEP風(fēng)險(xiǎn)無(wú)明顯影響[22]。在EST情況下的球囊直徑增加也不增加PEP風(fēng)險(xiǎn)[23]。

6．內(nèi)鏡鼻膽管引流術(shù)(endoscopic nasobiliary drainage, ENBD)：ERCP術(shù)后ENBD能有效引流膽汁，降低膽道壓力，避免膽汁反流入胰管，減少殘余結(jié)石及乳頭水腫引起的胰管壓力增高，從而減少了胰腺炎的發(fā)生。置入4 Fr鼻膽管較6Fr鼻膽管的PEP發(fā)生率明顯減低(3.7%比15.7%)，且更舒適[24]。

7．操作者的配合：目前國(guó)內(nèi)多數(shù)醫(yī)院的ERCP操作均為術(shù)者和助手合作完成，這就需要術(shù)者和助手之間極高的默契，即便是具有豐富操作經(jīng)驗(yàn)的ERCP醫(yī)師，在和陌生或初學(xué)ERCP的助手合作時(shí)仍會(huì)影響插管成功率。助手操作導(dǎo)絲存在導(dǎo)絲進(jìn)入胰管過(guò)深、導(dǎo)絲用力過(guò)強(qiáng)等問(wèn)題，從而增加PEP風(fēng)險(xiǎn)。Buxbaum等[25]的一項(xiàng)RCT研究將498名患者隨機(jī)分成術(shù)者操作導(dǎo)絲組和助手操作導(dǎo)絲組，在兩組內(nèi)又分別設(shè)置括約肌切開(kāi)刀直徑3.9 Fr和4.4 Fr亞組。中期評(píng)價(jià)時(shí)發(fā)現(xiàn)術(shù)者操作導(dǎo)絲組的PEP發(fā)生率為2.8%，明顯低于助手操作導(dǎo)絲組的9.3%而終止試驗(yàn)。值得注意的是，上述結(jié)果是在導(dǎo)絲進(jìn)入胰管的次數(shù)無(wú)統(tǒng)計(jì)學(xué)差異的基礎(chǔ)上得出的。在切開(kāi)刀直徑與PEP相關(guān)性分析中，切開(kāi)刀直徑3.9 Fr組PEP發(fā)生率為3.7%，低于直徑4.4 Fr組，雖差異無(wú)統(tǒng)計(jì)學(xué)意義，但似乎3.9 Fr的切開(kāi)刀插管引起PEP的風(fēng)險(xiǎn)更低。

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10.3760/cma.j.issn.1674-1935.2017.06.001

053600 河北石家莊，河北醫(yī)科大學(xué)第二醫(yī)院消化科

姜慧卿，Email: jianghq@aliyun.com

2017-01-18)

屠振興)