【作者】 邵黎明；

【导师】 蔡建庭；

【作者基本信息】 浙江大学 ， 内科学， 2010， 博士

【摘要】 至目前为止,ERCP (Endoscopic retrograde cholangiopancreatography, ERCP)术后胰腺炎(post-ERCP pancreatitis, PEP)仍然是ERCP最常见,也是最严重的一种并发症。根据定义的不同,ERCP术后胰腺炎的发生率在1%-40%之间,但大多数前瞻性研究表明,1.3%-6.7%的发生率更为常见。总的说来,目前预防PEP的方法可以分为两大类：药物性预防和技术性预防。常见的药物包括：皮质激素、非甾体类抗炎药(non steroidal anti-inflammatory drugs, NSAIDs)、生长抑素及其类似物、加贝酯、别嘌呤醇、硝酸甘油等。然而,除了NSAIDs已被最近的一项荟萃分析证明有效外,其他大多数药物的疗效都还未肯定。此外,没有一个药物已在临床广泛使用。目前,最常见的技术性预防PEP的方法是：胰管(pancreatic duct, PD)支架植入和导丝辅助插管(wire-guided cannulation, WGC).许多研究以及荟萃分析认为,在高危患者中预防性地放置胰管支架确实能够显著减少PEP的发生率。但是导丝辅助插管在预防PEP中的作用缺尚未在内镜医生达成共识。本研究通过荟萃分析的方法,对硝酸甘油及导丝辅助插管在预防PEP中的作用做一探究。第一部分荟萃分析：硝酸甘油在预防ERCP术后胰腺炎中的作用目的：将目前所有有关硝酸甘油预防ERCP术后胰腺炎的随机对照试验(randomized controlled trial, RCT)整合起来,将结果做一荟萃分析,来从而来评价硝酸甘油在预防ERCP术后胰腺炎中的作用。方法：从以下的数据库中检索符合要求的试验：中文数据库,包括中国生物医学文献数据库(Chinese Bimedical Literature Database, CBM),中国知网数据库(National Knowledge Infrastructure, CNKI),万方数据库及维普中文科技期刊数据库；外文数据库,包括PubMed, EMBASE, the Cochrane Library及the Science Citation Index。此外,检索国际会议摘要及所有检出论文的参考文献。检索的关键词为：硝酸甘油,胰腺炎,经内镜逆行胰胆管造影,ERCP及预防。结果：共检出7篇RCT,病人总数为1836人。荟萃分析的结果表明硝酸甘油能够显著减少PEP的发生率(RR 0.55; 95%CI:0.40-0.76; P=0.0002),但不能显著减少中-重度PEP的发生率(RR0.69;95%CI:0.42-1.15;P=0.15);随后的敏感性分析证实了这个结果。用硝酸甘油预防PEP的需治疗数(number of patients need to treat, NTT)为21。亚组分析：表明舌下给药能显著减少PEP的发生率(P=0.001),而经皮肤(P=0.05)及静脉给药(P=0.27)则没有显著性差异。硝酸甘油的副作用主要为头痛和低血压。结论：1.预防性使用硝酸甘油能显著减少ERCP术后胰腺炎的发生率,但不能显著减少中重度ERCP术后胰腺炎的发生率。2.舌下含服硝酸甘油能显著减少ERCP术后胰腺炎的发生率,通过皮肤贴膜给药则需要更多的随机对照试验来确证。3.舌下或经皮肤给药相对安全,且给药方便；静脉给药易引起较严重的血流动力学紊乱。4.今后的随机对照试验应有足够大的样本量；并且探寻硝酸甘油最佳的给药剂量。[关键词]ERCP术后胰腺炎；硝酸甘油；荟萃分析；随机对照试验第二部分荟萃分析：导丝辅助插管在预防ERCP术后胰腺炎中的作用目的：将目前所有比较导丝辅助插管及常规造影剂辅助插管在预防ERCP术后胰腺炎上差异的随机对照试验整合起来,将结果做一荟萃分析,来从而来评价导丝辅助插管在预防ERCP术后胰腺炎中的作用。方法：从以下的数据库中检索符合要求的试验：中文数据库,包括中国生物医学文献数据库(Chinese Bimedical Literature Database, CBM),中国知网数据库(National Knowledge Infrastructure, CNKI),万方数据库及维普中文科技期刊数据库；外文数据库,包括PubMed, EMBASE, the Cochrane Library及the Science Citation Index。此外,检索国际会议摘要及所有检出论文的参考文献。检索的关键词为：导丝,胰腺炎,经内镜逆行胰胆管造影,ERCP及插管。结果：共检出4篇RCT,病人总数为1431人。荟萃分析的结果表明,导丝辅助插管并没有显著减少PEP的发生率(RR0.34；95％CI:0.10-1.17；P=0.09).亚组分析结果表明,去除1项交叉试验后,导丝辅助插管能有效地减少PEP的发生(RR 0.20: 95％CI:0.09-0.40；P<0.0001)；在应用预切割技术的试验中,导丝辅助插管较之常规插管能显著减少PEP的发生率(RR0.23；95％CI:0.11-0.48；P=0.0001).导丝辅助插管有助于提高首次插管的成功率(RR1.14；95％CI:1.07-1.21；P=0.0001)；并且减少预切割技术的使用率(RR0.68；95％CI:0.51-0.91；P=0.009).导丝辅助插管的副作用很少见。结论：1.导丝辅助插管尚不能显著减少ERCP术后胰腺炎的发生率,需要更多设计良好的随机对照试验来进一步证实其在ERCP术后胰腺炎的预防作用。2.导丝辅助插管可以提高ERCP首次插管的成功率,减少插管时预切割技术的使用率。3.导丝辅助插管相对于常规造影剂插管是安全的。更多还原

【Abstract】 To date, acute pancreatitis remains the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The incidence of post-ERCP pancreatitis (PEP) varies from 1% to 40%, partly as a result of the definition of PEP, but figures of 1.3% to 6.7% are typical in large prospective studies.Generally, ways to prevent of PEP can be divided into two categories: pharmacological and mechanical. Pharmacological agents, including steroids, non-steroidal anti-inflammatory drugs (NSAIDs), somatostatin and its analogue, allopurinol, gabexate and nitroglycerin, have been studied in relation to their potential use for the prevention of PEP. However, most pharmacological prevention has not been proved effective, although rectal non steroidal anti-inflammatory drugs (NSAIDs) were reported to be efficacious in a recent meta-analysis. Furthermore, no pharmaological agents are widely used in routine clinical practice. Panreatic duct (PD) stent placement and wire-guided cannulation (WGC) are the most two common endoscopic techniques used in reducing PEP. The prophylactic use of PD stent in patients at high risk has become standard of care, whereas the use of WGC for PEP has not reached a consensus by endoscopists.The objective of this research is to evaluate the effect of prophylactic nitroglycerin and WGC for the prevention of PEP by performing a meta-analysis.Part One Meta-Analysis:nitroglycerin for the prevention of post-ERCP pancreatitisObjective:To evaluate the effect of prophylactic nitroglycerin in the prevention of PEP by performing a meta-analysis of randomized controlled trials (RCTs).Methods:Electronic databases, including Chinese Bimedical Literature Database (CBM), National Knowledge Infrastructure (CNKI), Wanfang Periodical Database, Weipu Periodical Database, PubMed, EMBASE, the Cochrane library, and the Science Citation Index, were searched to retrieve relevant trials. In addition, meeting abstracts and the reference lists of retrieved articles were reviewed for further relevant studies. The search terms were’glyceryl trinitrate’,’nitroglycerin’,’pancreatitis’,’endoscopic retrograde cholangiopancreatography’,’ERCP’,’prevention’and’prophylaxis’.Results:Seven RCTs, enrolling a total of 1836 patients, were included. Meta-analysis of these trials indicated a significant association between the use of nitroglycerin and the reduction of PEP (RR 0.55; 95%CI:0.40-0.76; P= 0.0002); while the incidence of moderate or severe PEP was not significantly reduced by nitroglycerin (RR 0.69; 95%CI:0.42-1.15; P= 0.15). Subsequent sensitive analyses confirmed these results. The pooled need to treat (NNT) with nitroglycerin to prevent one episode of pancreatitis is 21 patients. Subgroup analyses suggested that nitroglycerin administered by the sublingual route may be useful (P=0.001); while administration of nitroglycerin by the transdermal route did not reach statistical significance (P=0.05). The main side effects of nitroglycerin were headache and hypotension.Conclusion:1. Prophylactic use of nitroglycerin can significantly reduce the incidence of PEP; while the incidence of moderate or severe PEP was not significantly reduced by nitroglycerin.2. Administration of nitroglycerin by the sublingual route can significantly reduce the incidence of PEP; while the effects of administration by the transdermal route require further studies to confirm.3. Administration by the sublingual or transdermal route is relatively safe; however, the intravenous way may result severe hemodynamic instability.4. Sample sizes of future RCTs must be sufficient to detect significant differences; and it is better to perform a dose-ranging study to explore the optimum dosage. Part Two Meta-Analysis:Wire-Guided Cannulation for the prevention of post-ERCP pancreatitisObjective:To assess the overall effect of WGC for PEP compared with conventional contrast-assisted cannulation by carrying out a meta-analysis of all available RCTs.Methods:Electronic databases, including Chinese Bimedical Literature Database (CBM), National Knowledge Infrastructure (CNKI), Wanfang Periodical Database, Weipu Periodical Database, PubMed, EMBASE, the Cochrane library, and the Science Citation Index, were searched to retrieve relevant trials. In addition, meeting abstracts and the reference lists of retrieved articles were reviewed for further relevant studies. The search terms were’guidewire’,’guide wire’,’endoscopic retrograde cholangiopancreatography’,’ERCP’,’pancreatitis’and’cannulation’.Results:Four RCTs, enrolling a total of 1431 patients, were included. The meta-analysis failed to indicate a significant association between the use of WGC and the reduction of PEP (RR 0.34; 95%CI:0.10-1.17; P= 0.09). Subgroup analysis including trials without cross-over design showed a significant benefit with the use of WGC in reducing PEP (RR 0.20; 95%CI:0.09-0.40; P＜0.00001) and trials with precut used also indicated a significant differences between the two groups (RR 0.23; 95%CI:0.11-0.48; P=0.0001). Primary cannulation success was significantly greater with WGC compared with conventional contrast-guided cannulation (RR 1.14; 95%CI:1.07-1.21; P=0.0001); the need for precut was significantly less with WGC compared with conventional contrast-guided cannulation (RR 0.68; 95%CI:0.51-0.91; P=0.009). Complications attributable to guidewires used for ERCP were infrequent.Conclusion:1. This meta-analysis showed only a non-significant reduction in the rate of PEP with the use of WGC. Further well-designed RCT are still required to confirm the effect of WGC.2. The use of the guide wire not only increases the primary cannulation rate but also reduces the need for precut.3. Compared with conventional contrast-guided cannulation, WGC is also safe.更多还原