经内镜逆行胰胆管造影术后胰腺炎的高危因素研究进展

目前,随着内镜相关治疗技术的成熟,ERCP在国内开展也日趋广泛,但ERCP术后胰腺炎（post—ERCP pancreatitis,PEP）发生率也有不同程度增加。尽管多数文献报道其发生率在1％～40％,但值得注意的是仍有5％PEP患者可发展为重症胰腺炎,     

加贝酯预防内镜逆行胰胆管造影术后胰腺炎的随机对照试验的荟萃分析

内镜逆行胰胆管造影术（ERCP）是肝胆胰疾病的重要诊治手段之一，然而，ERCP可引起急性胰腺炎（AP）并致死。有报道内镜逆行胰胆管造影术后胰腺炎（PEP）的发生率在1％～40％，而术后高淀粉酶血症发生率可高达70％。其中约10％PEP可发展为重症胰腺炎，危及患者生命。目前认为蛋白酶活性在AP发病过程中起关键作用，抑制蛋白酶活性可对AP起治疗作用。Cavallini等报道在ERCP术前用蛋白酶抑制剂加贝酯进行预防性治疗可降低PEP的发生，而其他一些研究认为该药仅有边缘效应。因此，有必要用荟萃分析方法对已有研究结果进行系统定量的综合分析，以提高研究结论的可信性。     

ERCP术后胰腺炎的药物预防进展

ERCP术后胰腺炎（post ERCP pancreatitis，PEP）定义为：ERCP术后持续24h腹痛同时伴有血淀粉酶升高3倍以上，并使患者住院时间延长2d以上。该定义为多数研究所接受，但仍有一些研究将血淀粉酶升高5倍以上或测量血脂肪酶作为划分PEP的依据。由于各研究采用的PEP的定义不尽相同。接受ERCP治疗的人群条件不同以及各研究中心技术条件的差别，近期报道的PEP发生率波动在1％～30％。但大多数非选择性的前瞻性研究认为PEP发生率约为2％～9％。多变量分析研究表明PEP发生的危险因素，详见表1。尽管近年来ERCP技术日益普及和成熟，但PEP的发生率并未明显下降，现着重将药物方面预防PEP的进展综述如下。     

奥曲肽预防ERCP术后胰腺炎的系统评价

近年来，随着内镜下逆行胰胆管造影术（endoscopic retrograde cholangiopancreatography，ERCP）技术的改进和普及，使越来越多的患者免于手术也得到了很好的治疗，并明显降低了并发症。但ERCP术后胰腺炎（post—ERCP pancreatitis，PEP）的发生率却无明显变化，成为目前ERCP术后最常见和严重的并发症。在众多前瞻性的报道中，PEP的发生率为1％～14％。PEP不但患者痛苦、增加住院时间、费用，而且严重时甚至会危及生命，因此，如何预防及控制PEP的发生是临床医生广泛关注的问题。     

ERCP术后胰腺炎的影响因素分析

目的探讨诊断性与治疗性ERCP术后引发AP的高危因素及防范措施。方法采用单因素及多因素变量分析方法，对54例行诊断与治疗性ERCP的患者进行队列研究。结果54例患者中，3例（5，6％）并发ERCP术后胰腺炎（PEP），其中1例为诊断性ERCP，2例为诊疗性ERCP，ERCP术后胰腺炎均为轻症，经内科综合治疗后均痊愈出院。与PEP相关的主要因素有多次插管、多次胰管造影、导丝多次进入胰管、导丝引导插管、术中腹痛、全胰管显影、既往有胰腺炎病史等。其中，多次插管、胰管多次造影以及术中腹痛为高危因素。结论PEP与患者自身因素及医师操作技术有关，有效避免或减少这些高危因素的发生可预防PEP。     

双氯芬酸钠预防ERCP术后胰腺炎的机制

内镜逆行胰胆管造影术（ERCP）最常见和最严重的并发症是术后胰腺炎（post-ERCP pancreatitis,PEP）,发生率为1％～ 10％ ,高危患者发生率可达30％ .因此,预防PEP是临床研究的热点问题.研究表明,非甾体类抗炎药（NSAIDs）具有预防PEP的临床疗效.Elmunzer等和Dai等的荟萃分析亦证实NSAIDs能降低PEP发生率.NSAIDs是通过促进NSAID激活基因（NSAID activated gene,NAG-1）的表达发挥抗炎作用.近年有研究证实,双氯芬酸钠同样具有预防PEP发生的作用.本研究应用双氯芬酸钠防治PEP,观察患者血清NAG-1水平的变化,探讨其作用机制.     

胰管支架预防高危ERCP术后胰腺炎的荟萃分析

内镜逆行胰胆管造影术后胰腺炎（post—ERCPpancreati—tis,PEP）的发生率较高,最近～项对21篇前瞻性研究的系统调查发现PEP的发生率为3．07％（高危者可达30％～50％）,PEP引起的死亡率为0．11％。药理学方式预防PEP大多是不成功的。多项随机对照试验对经十二指肠乳头留置胰管支架进行评估,认为预防性胰管支架可作为预防胰腺炎的有效手段。     

胰管支架置入术预防逆行胰胆管造影术后胰腺炎高危患者PEP及高淀粉酶血症研究

[目的]研究逆行胰胆管造影(ERCP)术后放置胰管支架对胰腺炎高危患者ERCP术后胰腺炎(PEP)和高淀粉酶血症的预防作用.[方法]回顾性分析2006年3月～2012年6月在我科住院需行ERCP治疗的PEP高危患者123例的临床资料.根据术后是否放置胰管支架,将其分为胰管支架组53例(放置支架)和对照组70例(未放置支架).以Cotton标准诊断PEP和高淀粉酶血症,比较2组患者术前、术后6h血清淀粉酶水平,评估2组患者术后PEP和高淀粉酶血症的发生率;评估ERCP术后血清淀粉酶恢复正常的时间、PEP的发生率,分析PEP发生的高危因素.[结果]所有患者术前血清淀粉酶均正常;ERCP术后6h血清淀粉酶水平:胰管支架组(357.7±198.3)U/L,低于对照组(484.7±376.9)U/L;术后PEP的发生率:胰管支架组13例(24.5％),对照组39例(55.7％);术后高淀粉酶血症的发生率:胰管支架组22例(40.2％),对照组14例(20.0％);重症胰腺炎的发生率:胰管支架组0例(00.0％),对照组6例(8.57％);术后淀粉酶恢复正常的时间:胰管支架组为2.45 d;对照组为7.85d,以上指标2组比较差异均有统计学意义(均P＜0.05).[结论]ERCP术后在高危PEP人群中应用胰管支架置入术可有效降低PEP和高淀粉酶血症患者的淀粉酶水平;明显缩短术后PEP及高淀粉酶血症恢复正常的时间;明显缩短患者总住院时间.     

选择性插管对ERCP术后胰腺炎的预防作用

目的研究选择性插管对ERCP术后胰腺炎的预防作用。方法随机抽取在我院2009年至2011年因胆系疾病行ERCP检查和治疗的212例患者,按随机数字法分成常规插管造影组（常规组）100例和导丝超选组（导丝组）112例,监测两组血清淀粉酶波动情况,统计两组ERCP术后胰腺炎（PEP）发生率,回顾性分析选择性插管和PEP发生率的关系。结果两组插管成功率无统计学差异（P〉0.05）,常规组超作时间较导丝组长,常规组PEP发生率为13%,明显高于导丝组的5.36%（P〈0.05）,常规组有4例出现重症PEP,导丝组有3例重症PEP。结论 ERCP操作中应用导丝进行目标胆管选择性插管不能明显提高插管成功率,但能有效降低PEP发生率。     

胰管支架预防困难胆管插管ERCP术后急性胰腺炎的前瞻性研究

目的探讨经内镜逆行胰胆管造影术（ERCP）中置入胰管支架对困难胆管插管患者ERCP术后急性胰腺炎（PEP）的预防效果。方法120例行ERCP诊疗发生困难胆管插管的患者采用随机数字表法随机分成2组,一组术中置入胰管支架（观察组）,另一组未置入（对照组）,对比分析2组ERCP术后高淀粉酶血症、PEP的发生率以及术后患者腹痛评分结果。结果观察组发生ERCP术后高淀粉酶血症15例（27．3％）,PEP5例（8．3％）,无一例重症PEP,术后患者腹痛评分（3．82±1．48）分;对照组发生ERCP术后高淀粉酶血症18例（30．0％）,PEP14例（23．3％）,重症PEP2例（3．3％）,术后患者腹痛评分（4．78±1．93）分。2组ERCP术后高淀粉酶血症发生率比较,差异无统计学意义（P〉0．05）;观察组PEP、重症PEP发生率以及术后患者腹痛评分均明显低于对照组,差异均有统计学意义（P〈0．05）。结论置入胰管支架可以有效降低胆管插管困难所引起的PEP的风险,并能有效缓解患者术后疼痛,具有较好的临床应用价值。     

Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study

BACKGROUND: Pancreatitis is the most frequent complication of ERCP. Injury to the papilla during ERCP could obstruct pancreatic duct outflow and initiate pancreatitis. A randomized prospective study was performed to evaluate the effect of pancreatic duct stent placement on the frequency and severity of post-ERCP pancreatitis in a selected group of patients. METHODS: The study group consisted of patients over 18 years of age at high risk for post-ERCP pancreatitis because of a difficult cannulation, sphincter of Oddi manometry, and/or the performance of endoscopic sphincterotomy. Patients were prospectively randomized to have a pancreatic duct stent placed or no stent upon completion of the ERCP. The endoprosthesis used was either a 5F nasopancreatic catheter or 5F, 2-cm long pancreatic stent. Study endpoints were the frequency and severity of post-ERCP pancreatitis. RESULTS: Patients undergoing pancreatic duct stent placement had a lower frequency of post-ERCP pancreatitis as compared with those in the control group (28% vs. 5%; p < 0.05). Pancreatitis tended to be less severe in patients who had pancreatic duct drainage. CONCLUSIONS: Pancreatic duct stent insertion after ERCP reduces the frequency of post-ERCP pancreatitis in patients at high risk for this complication.     

胰管支架预防高危ERCP术后胰腺炎的临床分析

目的 观察胰管支架置人预防高危患者内镜逆行胰胆管造影（ERCP）术后胰腺炎及高淀粉酶血症的效果.方法 将确定有ERCP指征并符合纳入标准的72例高危患者按照随机数字表法分为胰管支架组和对照组,每组36例.比较两组术后3h、24 h血清淀粉酶水平及高淀粉酶血症、急性胰腺炎、重症胰腺炎的发生率.结果 胰管支架组术后3h和术后24 h血淀粉酶值分别为（128.68±173.35） U/L和（92.41±88.44） U/L,均低于对照组（432.37 ±515.20） U/L和（465.89±736.54） U/L,差异有统计学意义（P＜0.05）;胰管支架组术后高淀粉酶血症、急性胰腺炎、重症胰腺炎的发生率分别为5.6％、2.8％、0,对照组为22.2％、16.7％、11.1％,两组比较差异有统计学意义（P＜0.05）.结论 胰管支架置入能明显降低高危患者ERCP术后高淀粉酶血症、急性胰腺炎及重症胰腺炎的发生率.     

Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP

OBJECTIVES: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Many medications have been used to prevent this complication. We aimed to evaluate the efficacy of rectally administered indomethacin for the prevention of post-ERCP pancreatitis. METHODS: During 18 months, all eligible patients who underwent ERCP were enrolled in this study. In a double-blind randomized trial, patients received a suppository containing indomethacin, 100 mg, or an inert placebo immediately before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. RESULTS: A total of 490 patients entered the trial, of which half received indomethacin. Twenty-two patients developed pancreatitis; seven cases in the indomethacin group and 15 in the placebo group (P=0.06). Pancreatic duct injection (OR=3.0, 95% CI: 1.3-7.4), pancreatic duct cannulation more than once (OR=4.2, 95% CI: 1.7-10.0), and age less than 60 yr (OR=2.7, 95% CI: 1.0-7.1) were shown to be significant risk factors for developing post-ERCP pancreatitis. In patients who underwent pancreatography with or without cholangiography, the risk of pancreatitis was significantly lower in the indomethacin group compared with the control group (P=0.01, RRR=88%, ARR=0.16, NNT=6). Moderate to severe pancreatitis was significantly higher in the placebo group (P= 0.03). CONCLUSIONS: This trial shows that rectal indomethacin given immediately before ERCP can reduce the incidence and severity of post-ERCP pancreatitis.     

Can somatostatin prevent post‐ERCP pancreatitis? Results of a randomized controlled trial

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), occurring in 1-10% of patients. Several substances have been used, with negative results, in an attempt to prevent this complication. METHODS: We performed a double-blind randomized trial in 372 consecutive patients undergoing diagnostic or therapeutic ERCP to evaluate the role of somatostatin in preventing post-ERCP pancreatitis. The first group received continuous somatostatin infusion for 12 h starting 30 min before ERCP, the second group received a bolus intravenous injection of somatostatin at the time of cannulation of the papilla, and the third group received a placebo. RESULTS: Two patients in each of the somatostatin groups (1.7%) and 12 patients in the placebo group (9.8%) developed pancreatitis (P<0.05). Serum amylase levels 5 and 24 h after the procedure were lower in both groups that received somatostatin than in the placebo group (P<0.05). CONCLUSION: Somatostatin is useful in preventing post-ERCP pancreatitis. Further studies must be designed to investigate the cost-effectiveness of the drug and to determine the ideal administration route and dosage.     

Nifedipine for prevention of post-ERCP pancreatitis: a prospective,double-blind randomized study

BACKGROUND: Pancreatitis is the most common complication of ERCP. Calcium channel inhibitors have been shown to prevent the development of experimental pancreatitis. The aim of this randomized, placebo-controlled trial was to determine whether the calcium channel blocker nifedipine prevents post-ERCP pancreatitis. METHODS: Patients referred for ERCP were enrolled. Those being treated with a calcium channel inhibitor and those with acute or chronic pancreatitis were excluded. Nifedipine or placebo was administered orally less than 3 hours before and within 6 hours after ERCP. The main outcome measure was the number of cases of post-ERCP pancreatitis; a secondary outcome was the rate of post-ERCP pain (without pancreatitis) that persisted for 12 or more hours. RESULTS: One hundred fifty-five patients (70 women, 85 men; mean [SD] age 65.8 [18.2] years; range, 23-97 years) were enrolled and randomized to receive nifedipine (76 patients) or placebo (79 patients). The two groups were comparable. Procedures performed were retrograde diagnostic cholangiopancreatography alone (n = 33), biliary sphincterotomy (n = 31), stone extraction (n = 39), stent placement (n = 37), sphincteroplasty (n = 5), and other (n = 3). ERCP was unsuccessful in 5 patients. A single case of severe pancreatitis was observed (placebo group). The rate of post-ERCP pancreatitis was not different between groups (nifedipine, 10 patients, 13.2%; placebo, 14 patients, 17.7%; p = 0.4). The frequency of post-ERCP pain was not different between the groups. The only independent predictor of post-ERCP pancreatitis was difficult cannulation in both groups (OR = 3.78: 95% CI [1.25, 11.45]). CONCLUSION: This study failed to demonstrate a significant effect of nifedipine in the prevention of post-ERCP pancreatitis. A multicenter trial with greater statistical power would be needed to demonstrate a benefit for this drug.     

ERCP术后急性胰腺炎药物预防临床研究现状

逆行胰胆管造影术后急性胰腺炎(PEP)是逆行胰胆管造影最常见的并发症,发生率1%~40%。药物预防PEP临床研究已取得一定进展,生长抑素、加贝酯等有一定临床疗效,但许多药物临床效果不令人满意。     

NSAIDs for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography:Ready for prime time?

Acute pancreatitis is the most common and the most fearful complication of endoscopic retrograde cholangiopancreatography (ERCP). Prevention of post-ERCP pancreatitis has therefore been of great interest to endoscopists performing ERCP procedures. So far, only pancreatic duct stenting during ERCP and rectal administration of a non-steroidal anti-inflammatory drug (NSAID) prior to or immediately after ERCP have been consistently shown to be effective for prevention of post-ERCP pancreatitis. This commentary focuses on a short discussion about the rates, mechanisms, and risk factors for post-ERCP pancreatitis, and effective means for its prevention with emphasis on the use of NSAIDs including a recent clinical trial published in The New England Journal of Medicine by Elmunzer et al([11]).     

Ulinastatin shows preventive effect on post-endoscopic retrograde cholangiopancreatography pancreatitis in a multicenter prospective randomized study

BACKGROUND AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is a useful diagnostic and therapeutic procedure; however, ERCP occasionally causes post-ERCP pancreatitis. The administration of gabexate mesilate has been reported to be effective for the prevention for post-ERCP pancreatitis when given during and after the procedure. The aim of the present study was to investigate the preventive effect of the novel protease inhibitor ulinastatin on post-ERCP pancreatitis. METHODS: One hundred and thirty-nine patients who underwent the ERCP procedure were studied. These patients were randomly divided into three groups based on the agent and dose given during and following the ERCP procedure: gabexate mesilate (900 mg), high-dose ulinastatin (450 000 units) and low-dose ulinastatin (150 000 units). Serum amylase, interleukin (IL)-6 and IL-8 levels and plasma polymorphonuclear leukocyte elastase (PMN-E) activity were measured after ERCP. In addition, post-ERCP hyperamylasemia and post-ERCP pancreatitis were recorded. RESULTS: There were no significant differences in serum amylase, IL-6 and IL-8 levels and PMN-E activity after ERCP procedure between the three groups. Post-ERCP pancreatitis was observed in two (4.3%), three (6.5%) and four (8.5%) cases in the gabexate mesilate, high-dose ulinastatin and low-dose ulinastatin groups, respectively. Multiple logistic regression analysis showed that the addition of endoscopic sphincterotomy during the ERCP procedure was the only significant risk factor for the development of post-ERCP hyperamylasemia and post-ERCP pancreatitis (P = 0.03 and P = 0.04, respectively), but there was no significant difference in the occurrence of post-ERCP hyperamylasemia and post-ERCP pancreatitis between the three groups receiving different preventative treatments. CONCLUSION: The administration of low- and high-dose ulinastatin has similar effects to high-dose gabexate in the prevention of post-ERCP pancreatitis.     

Risk factors for post-ERCP pancreatitis: a prospective multicenter study

OBJECTIVES: Pancreatitis is the most common and serious complication of diagnostic and therapeutic ERCP. The aim of this study is to examine the potential patient- and procedure-related risk factors for post-ERCP pancreatitis in a prospective multicenter study. METHODS: A 160-variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and participating in a randomized controlled study evaluating whether prophylactic corticosteroids will reduce the incidence of post-ERCP pancreatitis. Data were collected prior to the procedure, at the time of procedure, and 24-72 h after discharge. Post-ERCP pancreatitis was diagnosed and its severity graded according to consensus criteria. RESULTS: Of the 1,115 patients enrolled, diagnostic ERCP with or without sphincter of Oddi manometry (SOM) was performed in 536 (48.1%) and therapeutic ERCP in 579 (51.9%). Suspected sphincter of Oddi dysfunction (SOD) was the indication for the ERCP in 378 patients (33.9%). Pancreatitis developed in 168 patients (15.1%) and was graded mild in 112 (10%), moderate in 45 (4%), and severe in 11(1%). There was no difference in the incidence of pancreatitis or the frequency of investigated potential pancreatitis risk factors between the corticosteroid and placebo groups. By univariate analysis, the incidence of post-ERCP pancreatitis was significantly higher in 19 of 30 investigated variables. In the multivariate risk model, significant risk factors with adjusted odds ratios (OR) were: minor papilla sphincterotomy (OR: 3.8), suspected SOD (OR: 2.6), history of post-ERCP pancreatitis (OR: 2.0), age <60 yr (OR: 1.6), > or =2 contrast injections into the pancreatic duct (OR: 1.5), and trainee involvement (OR: 1.5). Female gender, history of recurrent idiopathic pancreatitis, pancreas divisum, SOM, difficult cannulation, and major papilla sphincterotomy (either biliary or pancreatic) were not multivariate risk factors for post-ERCP pancreatitis. CONCLUSION: This study emphasizes the role of patient factors (age, SOD, prior history of post-ERCP pancreatitis) and technical factors (number of PD injections, minor papilla sphincterotomy, and operator experience) as the determining high-risk predictors for post-ERCP pancreatitis.     

A prospective, randomized, placebo-controlled trial of transdermal glyceryl trinitrate in ERCP: effects on technical success and post-ERCP pancreatitis

BACKGROUND: Despite the recent improvement in techniques and patient selection, post-ERCP pancreatitis remains the most frequent and dreaded complication of ERCP. Recent studies suggest that pretreatment with glyceryl trinitrate (GTN) may prevent post-ERCP pancreatitis and improve cannulation success. OBJECTIVE: To evaluate the effect of transdermal GTN on ERCP cannulation success and post-ERCP pancreatitis. DESIGN: Prospective, double-blind, placebo-controlled trial. SETTING: Tertiary referral university hospital. PATIENTS: A total of 318 patients (mean age 62 years, 61% women) were randomized to either active (n = 155) or placebo (n = 163) arms. INTERVENTIONS: Active patch (GTN) versus placebo patch. MAIN OUTCOME MEASUREMENTS: Cannulation time and success. Post-ERCP pancreatitis rates. RESULTS: There was no significant difference between the active or placebo arms for the following: successful initial cannulation (96.8% vs 98.8%), deep cannulation (96.1% vs 98.8%), time to successful cannulation, use of guidewire (27% vs 25%) or needle knife (13% vs 13%), and post-ERCP pancreatitis (7.4% of placebo patients and 7.7% active patients). Multivariate analysis identified women, younger patients, pancreatogram, number of attempts on papilla, and poor pancreatic-duct emptying after opacification as risk factors for post-ERCP pancreatitis. Transdermal GTN did not reduce post-ERCP pancreatitis in any of the identified high-risk groups. CONCLUSIONS: Transdermal GTN did not improve the rate of success in ERCP cannulation or prevent post-ERCP pancreatitis in either average or high-risk patient groups.