依爾潘·艾山　高　峰

新疆醫(yī)科大學(xué)(830011)1　新疆維吾爾自治區(qū)人民醫(yī)院消化科2

內(nèi)鏡逆行胰膽管造影術(shù)后胰腺炎的研究進(jìn)展

依爾潘·艾山1高峰2*

新疆醫(yī)科大學(xué)(830011)1新疆維吾爾自治區(qū)人民醫(yī)院消化科2

胰腺炎是內(nèi)鏡逆行胰膽管造影術(shù)(endoscopic retrograde cholangiopancreatography, ERCP)的術(shù)后最常見(jiàn)并發(fā)癥，發(fā)生率約為3%~5%[1]。Andriulli等[2]對(duì)16 855例患者研究發(fā)現(xiàn)，ERCP術(shù)后約3.5%的患者發(fā)生胰腺炎,0.4%為重度胰腺炎，其中0.11%發(fā)生死亡。ERCP術(shù)后胰腺炎(post-ERCP pancreatitis, PEP)的發(fā)生與多種因素相關(guān)。本文就PEP的研究進(jìn)展作一綜述。

一、PEP的診斷

PEP診斷標(biāo)準(zhǔn)：①ERCP術(shù)后持續(xù)腹痛；②血清淀粉酶>3倍標(biāo)準(zhǔn)值上限，持續(xù)>24 h；③延長(zhǎng)住院時(shí)間>1 d。PEP的嚴(yán)重程度根據(jù)住院時(shí)間的長(zhǎng)短以及是否需行干預(yù)措施決定。PEP的嚴(yán)重程度分為輕度(臨床胰腺炎，血清淀粉酶>3倍正常值上限，持續(xù)>24 h，需將無(wú)針對(duì)性或針對(duì)性處理延長(zhǎng)2~3 d)、中度(臨床胰腺炎需住院治療4~10 d)和重度(臨床胰腺炎住院時(shí)間>10 d、出血性胰腺炎、胰腺壞死或假性囊腫、需行介入治療如經(jīng)皮引流或手術(shù))[3]。

二、PEP發(fā)生的危險(xiǎn)因素和保護(hù)因素

導(dǎo)致PEP的危險(xiǎn)因素諸多，包括患者相關(guān)危險(xiǎn)因素、內(nèi)鏡相關(guān)危險(xiǎn)因素和手術(shù)相關(guān)危險(xiǎn)因素，多種危險(xiǎn)因素共存可發(fā)揮累積效應(yīng)。年輕、女性、血清膽紅素正常、曾在ERCP術(shù)后發(fā)生胰腺炎、Oddi括約肌功能障礙者發(fā)生PEP的風(fēng)險(xiǎn)較高[3]。Li等[4]的研究發(fā)現(xiàn)，服用胰毒性藥物如雌激素、硫唑嘌呤、丙戊酸、美沙拉秦、嗎啡衍生物以及潑尼松等可增加PEP的發(fā)生率。此外，內(nèi)鏡下插管困難、胰管注入造影劑、括約肌預(yù)切開術(shù)、胰管括約肌切開術(shù)、小乳頭括約肌切開術(shù)、膽管支架術(shù)等亦是PEP發(fā)生的危險(xiǎn)因素[3，5]。

研究[6-7]顯示，吸煙、慢性肝臟疾病可降低PEP的發(fā)生率，是PEP的保護(hù)因素。

三、PEP的發(fā)生機(jī)制

PEP的發(fā)生機(jī)制：①乳頭和胰管插管引起的機(jī)械性損傷；②使用電刀行胰膽管括約肌切開術(shù)時(shí)出現(xiàn)熱損傷；③注射造影劑后進(jìn)入胰管時(shí)或用0.9% NaCl溶液行括約肌測(cè)壓時(shí)出現(xiàn)靜水傷；④造影劑注射后進(jìn)入胰管引起化學(xué)或過(guò)敏性損傷；⑤蛋白水解酶在胰管管腔內(nèi)激活引起酶損傷；⑥由內(nèi)鏡及其配件引起的感染[8]。

四、PEP的預(yù)防

1. ERCP技術(shù)

①插管：使用導(dǎo)絲引導(dǎo)下插管術(shù)能降低膽管插管術(shù)的難度，但Kobayashi等[9]對(duì)322例患者采用導(dǎo)絲引導(dǎo)下膽管插管術(shù)或常規(guī)插管術(shù)，結(jié)果顯示兩組PEP發(fā)生率和膽管插管成功率相似。Mariani等[10]的研究顯示，導(dǎo)絲引導(dǎo)下膽管插管術(shù)、胰管括約肌切開術(shù)以及注射造影劑三者引起PEP的概率無(wú)顯著差異。在ERCP手術(shù)過(guò)程中，操作者應(yīng)盡量減少插管次數(shù)、降低插管難度、避免插管所致的損傷，從而降低PEP的發(fā)生率。

②電灼：采用電刀行膽管或胰管括約肌切開術(shù)后的熱損傷可引起PEP。有研究[11]對(duì)純切電流與混合電流引起PEP的概率進(jìn)行比較，結(jié)果顯示純切電流與混合電流行括約肌切開術(shù)的PEP發(fā)生率差異無(wú)統(tǒng)計(jì)學(xué)意義。盡量避免使用電刀行膽管或胰管括約肌切開術(shù)，以降低PEP的發(fā)生率。

③胰管支架：有報(bào)道[12]指出，對(duì)插管困難、針刀預(yù)切以及Oddi括約肌功能障礙患者行膽管括約肌切開術(shù)、胰腺括約肌切開術(shù)、內(nèi)鏡下壺腹切除以及內(nèi)鏡球囊擴(kuò)張術(shù)后放置胰管支架可降低PEP的發(fā)生率以及嚴(yán)重程度。一項(xiàng)meta分析[13]對(duì)放置胰管支架與PEP發(fā)生率的相關(guān)性進(jìn)行了分析，結(jié)果顯示放置胰管支架組較未放置胰管支架組的PEP發(fā)生率顯著降低。胰管支架帶有一定的局限性，可發(fā)生胰管損傷、狹窄等并發(fā)癥，此外，支架放置失敗亦可發(fā)生胰腺炎。Freeman等[14]對(duì)225例ERCP高?；颊哌M(jìn)行前瞻性研究，3例患者胰管支架置入失敗，其中2例(66.7%)發(fā)生胰腺炎，222例患者置入成功，其中32例(14.4%)發(fā)生胰腺炎。

②其他抗炎制劑：有研究[19]表明糖皮質(zhì)激素可預(yù)防PEP，但有研究[20]指出預(yù)防性靜脈注射或口服皮質(zhì)類固醇不能降低PEP的發(fā)生率。白細(xì)胞介素-10(IL-10)是抗炎細(xì)胞因子。研究[21]發(fā)現(xiàn)，與安慰劑組(24%)相比，試驗(yàn)組ERCP術(shù)前30 min給予IL-10可顯著降低PEP的發(fā)生率(8%)，但Sherman等[22]的研究顯示，與安慰劑相比，IL-10降低PEP發(fā)生率無(wú)顯著優(yōu)勢(shì)。關(guān)于別嘌醇對(duì)PEP預(yù)防效果的研究結(jié)果亦存在矛盾。Bai等[23]的研究顯示，別嘌醇不能降低PEP的發(fā)生率，不推薦作為預(yù)防劑。然而Hauser等[24]指出，ERCP術(shù)前3 h口服別嘌醇(600 mg)可顯著降低PEP的發(fā)生率。

③減少胰腺分泌：生長(zhǎng)抑素及其類似物是胰腺外分泌的強(qiáng)效抑制劑。Lee等[25]的研究發(fā)現(xiàn)，生長(zhǎng)抑素有助于預(yù)防PEP。然而，Andriulli等[26]的研究顯示生長(zhǎng)抑素對(duì)預(yù)防PEP無(wú)明顯效果。因此，目前不推薦生長(zhǎng)抑素作為預(yù)防劑。降鈣素在胰腺炎中的作用備受關(guān)注，但研究顯示其對(duì)PEP無(wú)預(yù)防作用[27]。蛋白酶抑制劑可抑制參與急性胰腺炎炎癥級(jí)聯(lián)反應(yīng)的胰蛋白酶活性。諸多研究對(duì)甲磺酸加貝酯、萘莫司他、烏司他丁預(yù)防PEP進(jìn)行分析，但研究結(jié)果不盡一致。Seta等[28]進(jìn)行的meta分析顯示尚無(wú)確切證據(jù)證實(shí)蛋白酶抑制劑可預(yù)防PEP。

④抗菌藥物和抗氧化劑：目前僅有一項(xiàng)前瞻性隨機(jī)對(duì)照研究顯示，ERCP術(shù)前30 min靜脈給予頭孢他啶可顯著降低PEP的發(fā)生率，但由于此研究對(duì)照組未使用安慰劑而被認(rèn)為質(zhì)量較差[29]。因此，有關(guān)抗菌藥物對(duì)PEP的預(yù)防作用仍需進(jìn)一步研究。氧化應(yīng)激可能參與PEP發(fā)病，但Gu等[30]的研究顯示，與安慰劑相比，抗氧化劑在降低PEP發(fā)生率和嚴(yán)重程度方面無(wú)顯著優(yōu)勢(shì)。

五、結(jié)語(yǔ)

總之，PEP是ERCP的常見(jiàn)并發(fā)癥，可由多種因素導(dǎo)致。ERCP患者的選擇和術(shù)前評(píng)估相關(guān)危險(xiǎn)因素是預(yù)防PEP的關(guān)鍵。胰管支架對(duì)預(yù)防PEP起有一定作用，但具有局限性。NSAIDs直腸給藥是降低PEP發(fā)生率的有效方式，已在臨床廣泛應(yīng)用。其余藥物預(yù)防PEP的結(jié)論尚不明確，有待后續(xù)進(jìn)一步研究證實(shí)。

參考文獻(xiàn)

1 Sakai Y, Tsuyuguchi T, Hirata N, et al. Can endoscopic sphincterotomy be performed safely in elderly patients aged 80 years or older with pancreatic and biliary diseases? [J]. Hepatogastroenterology, 2013, 60 (126): 1251-1256.

2 Andriulli A, Loperfido S, Napolitano G, et al. Incidence rates of post-ERCP complications: a systematic survey of prospective studies[J]. Am J Gastroenterol, 2007, 102 (8): 1781-1788.

3 Abdel Aziz AM, Lehman GA. Pancreatitis after endoscopic retrograde cholangio-pancreatography[J]. World J Gastroenterol, 2007, 13 (19): 2655-2668.

4 Li N, Tieng A, Novak S, et al. Effects of medications on postendoscopic retrograde cholangiopancreatography pancreatitis[J]. Pancreatology, 2010, 10 (2-3): 238-242.

5 Wilcox CM, Phadnis M, Varadarajulu S. Biliary stent placement is associated with post-ERCP pancreatitis[J]. Gastrointest Endosc, 2010, 72 (3): 546-550.

6 DiMagno MJ, Spaete JP, Ballard DD, et al. Risk models for post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP): smoking and chronic liver disease are predictors of protection against PEP[J]. Pancreas, 2013, 42 (6): 996-1003.

7 Glomsaker T, Hoff G, Kval?y JT, et al. Patterns and predictive factors of complications after endoscopic retrograde cholangiopancreatography[J]. Br J Surg, 2013, 100 (3): 373-380.

8 Donnellan F, Byrne MF. Prevention of post-ERCP pancreatitis[J]. Gastroenterol Res Pract, 2012, 2012: 796751.

9 Kobayashi G, Fujita N, Imaizumi K, et al. Wire-guided biliary cannulation technique does not reduce the risk of post-ERCP pancreatitis: multicenter randomized controlled trial[J]. Dig Endosc, 2013, 25 (3): 295-302.

10Mariani A, Giussani A, Di Leo M, et al. Guidewire biliary cannulation does not reduce post-ERCP pancreatitis compared with the contrast injection technique in low-risk and high-risk patients[J]. Gastrointest Endosc, 2012, 75 (2): 339-346.

11Verma D, Kapadia A, Adler DG. Pure versus mixed electro-surgical current for endoscopic biliary sphincterotomy: a meta-analysis of adverse outcomes[J]. Gastrointest Endosc, 2007, 66 (2): 283-290.

12Feurer ME, Adler DG. Post-ERCP pancreatitis: review of current preventive strategies[J]. Curr Opin Gastroenterol, 2012, 28 (3): 280-286.

13Mazaki T, Mado K, Masuda H, et al. Prophylactic pancreatic stent placement and post-ERCP pancreatitis: an updated meta-analysis[J]. J Gastroenterol, 2014, 49 (2): 343-355.

14Freeman ML, Overby C, Qi D. Pancreatic stent insertion: consequences of failure and results of a modified technique to maximize success[J]. Gastrointest Endosc, 2004, 59 (1): 8-14.

15Murray B, Carter R, Imrie C, et al. Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography[J]. Gastroenterology, 2003, 124 (7): 1786-1791.

16Elmunzer BJ, Waljee AK, Elta GH, et al. A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis[J]. Gut, 2008, 57 (9): 1262-1267.

17Dai HF, Wang XW, Zhao K. Role of nonsteroidal antiin-flammatory drugs in the prevention of post-ERCP pancreatitis: a meta-analysis[J]. Hepatobiliary Pancreat Dis Int, 2009, 8 (1): 11-16.

18Ding X, Chen M, Huang S, et al. Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis[J]. Gastrointest Endosc, 2012, 76 (6): 1152-1159.

19Kahaleh M, Freeman M. Prevention and management of post-endoscopic retrograde cholangiopancreatography complications[J]. Clin Endosc, 2012, 45 (3): 305-312.

20Law R, Leal C, Dayyeh BA, et al. Role of immunosuppression in post-endoscopic retrograde cholangiopancreatography pancreatitis after liver transplantation: a retrospective analysis[J]. Liver Transpl, 2013, 19 (12): 1354-1360.

21Dumot JA, Conwell DL, Zuccaro G, et al. A randomized, double blind study of interleukin 10 for the prevention of ERCP-induced pancreatitis[J]. Am J Gastroenterol, 2001, 96 (7): 2098-2102.

22Sherman S, Cheng CL, Costamagna G, et al. Efficacy of recombinant human interleukin-10 in prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in subjects with increased risk[J]. Pancreas, 2009, 38 (3): 267-274.

23Bai Y, Gao J, Zhang W, et al. Meta-analysis: allopurinol in the prevention of postendoscopic retrograde cholangio-pancreatography pancreatitis[J]. Aliment Pharmacol Ther, 2008, 28 (5): 557-564.

24Hauser G, Milosevic M, Stimac D, et al. Preventing post-endoscopic retrograde cholangiopancreatography pancreatitis: what can be done?[J]. World J Gastroenterol, 2015, 21 (4): 1069-1080.

25Lee KT, Lee DH, Yoo BM. The prophylactic effect of somatostatin on post-therapeutic endoscopic retrograde cholangiopancreatography pancreatitis: a randomized, multicenter controlled trial[J]. Pancreas, 2008, 37 (4): 445-448.

26Andriulli A, Leandro G, Federici T, et al. Prophylactic administration of somatostatin or gabexate does not prevent pancreatitis after ERCP: an updated meta-analysis[J]. Gastrointest Endosc, 2007, 65 (4): 624-632.

27Freeman ML. Complications of endoscopic retrograde cholangiopancreatography: avoidance and management[J]. Gastrointest Endosc Clin N Am, 2012, 22 (3): 567-586.

28Seta T, Noguchi Y. Protease inhibitors for preventing complications associated with ERCP: an updated meta-analysis[J]. Gastrointest Endosc, 2011, 73 (4): 700-706.

29Vila JJ, Artifon EL, Otoch JP. Post-endoscopic retrograde cholangiopancreatography complications: How can they be avoided? [J]. World J Gastrointest Endosc, 2012, 4 (6): 241-246.

30Gu WJ, Wei CY, Yin RX. Antioxidant supplementation for the prevention of post-endoscopic retrograde cholangio-pancreatography pancreatitis: a meta-analysis of randomized controlled trials[J]. Nutr J, 2013, 12: 23.

(2015-01-05收稿；2015-03-04修回)

(2014-12-14收稿； 2015-02-23修回)

摘要胰腺炎是內(nèi)鏡逆行胰膽管造影術(shù)(ERCP)的術(shù)后常見(jiàn)并發(fā)癥。ERCP患者的選擇和術(shù)前評(píng)估相關(guān)危險(xiǎn)因素是預(yù)防ERCP術(shù)后胰腺炎(PEP)的關(guān)鍵。胰管支架對(duì)預(yù)防PEP有一定作用，但具有局限性。NSAIDs直腸給藥是降低PEP發(fā)生率的有效方式。其余藥物預(yù)防PEP的結(jié)論尚不明確。本文就PEP的研究進(jìn)展作一綜述。

關(guān)鍵詞胰腺炎；胰膽管造影術(shù), 內(nèi)窺鏡逆行；危險(xiǎn)因素；預(yù)防

Advances in Study on Post-endoscopic Retrograde Cholangiopancreatography PancreatitisYIERPANAishan1,GAOFeng2.1XinjiangMedicalUniversity,Urumqi(830011);2DepartmentofGastroenterology,People’sHospitalofXinjiangUygurAutonomousRegion,Urumqi

Correspondence to: GAO Feng, Email: xjgf@sina.com

AbstractPancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Patient selection and risk factors assessment are critical elements for preventing post-ERCP pancreatitis (PEP). Pancreatic stent plays a role in prevention of PEP, but with limitations. Rectal administration of NSAIDs is an effective way to reduce the incidence of PEP. Effect of other drugs for preventing PEP is unclear. This article reviewed the advances in study on PEP.

Key wordsPancreatitis;Cholangiopancreatography, Endoscopic Retrograde;Risk Factors;Prevention

通信作者*本文，Email: xjgf@sina.com

DOI:10.3969/j.issn.1008-7125.2015.08.015