Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography

BACKGROUND & AIMS: Acute pancreatitis following endoscopic retrograde cholangiopancreatography presents a unique opportunity for prophylaxis and early modification of the disease process because the initial triggering event is temporally well defined and takes place in the hospital. We report a prospective, single-center, randomized, double-blind controlled trial to determine if rectal diclofenac reduces the incidence of pancreatitis following cholangiopancreatography. METHODS: Entry to the trial was restricted to patients who underwent endoscopic retrograde pancreatography or had manometrically verified sphincter of Oddi hypertension. Immediately after endoscopy, patients were given a suppository containing either 100 mg diclofenac or placebo. Estimation of serum amylase levels and clinical evaluation were performed in all patients. RESULTS: A total of 220 patients entered the trial, and 110 received rectal diclofenac. Twenty-four patients developed pancreatitis (11%), of whom 7 received rectal diclofenac and 17 received placebo (P < 0.05). CONCLUSIONS: This trial shows that rectal diclofenac given immediately after endoscopic retrograde cholangiopancreatography can reduce the incidence of acute pancreatitis.     

Interleukin 10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography

BACKGROUND & AIMS: Prophylactic administration of interleukin (IL)-10 decreases the severity of experimental pancreatitis. Prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in humans is a unique model to study the potential role of IL-10 in this setting. METHODS: In a single-center, double-blind, randomized, placebo-controlled study, the effect of a single injection of 4 microg/kg (group 1) or 20 microg/kg (group 2) IL-10 was compared with that of placebo (group 0), all administered 30 minutes before therapeutic ERCP. The primary endpoint was the effect of IL-10 on serum levels of amylases and lipases measured 4, 24, and 48 hours after ERCP. The secondary objective was to evaluate changes in plasma cytokines (IL-6, IL-8, tumor necrosis factor) at the same time points and the incidence of acute pancreatitis in the 3 groups. Subjects undergoing a first therapeutic ERCP were eligible for inclusion. RESULTS: A total of 144 patients were included. Seven were excluded based on intention to treat (n = 1) or per protocol (n = 6). Forty-five, 48, and 44 patients remained in groups 0, 1, and 2, respectively. The 3 groups were comparable for age, sex, underlying disease, indication for treatment, type of treatment, and plasma levels of C-reactive protein (CRP), cytokines, and hydrolases at baseline. No significant difference was observed in CRP, cytokine, and hydrolase plasma levels after ERCP. Forty-three patients developed hyperhydrolasemia (18 in group 0, 14 in group 1, and 11 in group 2; P = 0.297), and 19 patients developed acute clinical pancreatitis (11 in group 0, 5 in group 1, 3 in group 2; P = 0.038). Two severe cases were observed in the placebo group. No mortality related to ERCP was observed. Logistic regression identified 3 independent risk factors for post-therapeutic ERCP pancreatitis: IL-10 administration (odds ratio [OR], 0.46; 95% confidence interval [95% CI], 0.22-0.96; P = 0.039), pancreatic sphincterotomy (OR, 5.04; 95% CI, 1.53-16.61; P = 0.008), and acinarization (OR, 8.19; 95% CI, 1.83-36.57; P = 0.006). CONCLUSIONS: A single intravenous dose of IL-10, given 30 minutes before the start of the procedure, independently reduces the incidence of post-therapeutic ERCP pancreatitis.     

Role of endoscopic retrograde cholangiopancreatography in acute pancreatitis

Endoscopic retrograde cholangiopancreatography （ERCP） is a useful tool in the evaluation and management of acute pancreatitis. This review will focus on the role of ERCP in specific causes of acute pancreatitis, including microlithiasis and gallstone disease, pancreas divisum, Sphincter of Oddi dysfunction, tumors of the pancreaticobiliary tract, pancreatic pseudocysts, and pancreatic duct injury. Indications for endoscopic techniques such as biliary and pancreatic sphincterotomy, stenting, stricture dilation, treatment of duct leaks, drainage of fluid collections and stone extraction will also be discussed in this review. With the advent of less invasive and safer diagnostic modalities including endoscopic ultrasound （EUS） and magnetic retrograde cholangiopancreatography （MRCP）, ERCP is appropriately becoming a therapeutic rather than diagnostic tool in the management of acute pancreatitis and its complications.     

Hyperamylasaemia and acute pancreatitis following endoscopic retrograde cholangiopancreatography

Hyperamylasaemia and acute pancreatitis are the more common complications of endoscopic retrograde cholangiopancreatography (ERCP). Ninety patients who underwent ERCP +/- endoscopic papillotomy were monitored for rises in the serum amylase and the development of acute pancreatitis. The incidence of hyperamylasaemia (greater than 300 IU/L) was significantly greater (p = 0.01) when the pancreatic duct was imaged (75%) than with bile duct imaging alone (33%). The incidence of acute pancreatitis following imaging of the pancreatic duct +/- bile duct was 11.3% and was found to be significantly increased in those patients (n = 9) who also underwent endoscopic papillotomy. Imaging of the biliary tree only +/- endoscopic papillotomy carried no significant risk of acute pancreatitis. In those patients who developed pancreatitis, the rise in serum amylase occurred early and was significantly higher at 2 h following ERCP. These findings may help to identify patients who are at risk of developing this complication.     

经内镜逆行胰胆管造影术后急性胰腺炎与高淀粉酶血症对比观察

目的 比较经内镜逆行胰胆管造影术(ERCP)后急性胰腺炎(PEP)与高淀粉酶血症(PEHA)患者的临床特点及影响因素,为预防病情进展提供依据。 方法 选取武汉大学人民医院2017年1月-2019年8月住院行ERCP的患者117例,所有患者术前均预防性使用双氯芬酸钠栓塞肛。术后发生PEHA组77例,PEP组40例,比较2组患者临床特点及影响因素。符合正态分布的计量资料2组间比较采用t检验;不符合正态分布的计量资料2组间比较采用Mann-Whitney U检验;计数资料2组间比较采用χ2检验;采用多因素logistic回归分析PEP的独立影响因素。结果 术前ALP(Z=-2.518,P=0.012)、GGT(Z=-2.313,P=0.021)、TBil(Z=-2.978,P=0.003)、DBil(Z=-3.069,P=0.002)水平及术中是否行导丝进入胰管检查(χ2=4.176,P=0.041)在两组之间差异显著。进一步logistic回归分析结果显示,导丝进入胰管次数≥3次[优势比(OR)=2.469,95%可信区间(95%CI): 1.199~5.188,P=0.047]、ALP<125 U/L(OR=5.499,95%CI: 1.452~18.830,P=0.012)、TBil<22 μmol/L(OR=4.249,95%CI: 1.023~17.648,P=0.046)是影响PEP发生的独立危险因素。结论 即使预防性使用双氯芬酸钠栓剂,术前ALP、TBil水平正常及术中导丝多次进入胰管的患者更易发生PEP,需引起手术医师警惕。根据病情,术前及术后采取早期干预措施可能减少PEHA向PEP进展,减少中重度PEP的发生,改善预后。     

Intravenous bolus somatostatin after diagnostic cholangiopancreatography reduces the incidence of pancreatitis associated with therapeutic endoscopic retrograde cholangiopancreatography procedures: a randomised controlled trial

BACKGROUND: Previous studies suggested that somatostatin given before endoscopic retrograde cholangiopancreatography (ERCP) may reduce the incidence of post-ERCP pancreatitis. However, the routine use of somatostatin in all patients undergoing ERCP is not likely to be cost effective. This study evaluated whether intravenous bolus somatostatin given after diagnostic cholangiopancreatography could reduce the incidence of pancreatitis in a group of patients undergoing therapeutic ERCP procedures. METHODS: In a randomised, double blind, controlled trial, the effect of intravenous bolus somatostatin 250 microg given immediately after diagnostic cholangiopancreatography was compared with that of placebo in patients who required endoscopic sphincterotomy or other therapeutic procedures. The primary end point was the incidence of post-ERCP clinical pancreatitis, and a secondary end point was the incidence of hyperamylasemia. RESULTS: A total of 270 patients were randomised. The somatostatin group (n=135) and the placebo group (n=135) were comparable in age, sex, indications for treatment, and types of procedure. The frequencies of clinical pancreatitis (4.4% v 13.3%; p=0.010) and hyperamylasemia (26.0% v 38.5%; p=0.036) were both significantly lower in the somatostatin group compared with the placebo group. CONCLUSIONS: A single dose of intravenous bolus somatostatin, given immediately after diagnostic cholangiopancreatography, is effective in reducing the incidence of pancreatitis after therapeutic ERCP. This novel approach of administering prophylactic somatostatin may offer a cost effective prophylaxis for post-ERCP pancreatitis.     

Oral allopurinol to prevent hyperamylasemia and acute pancreatitis after endoscopic retrograde cholangiopancreatography

AIM： To assess the efficacy of allopurinol to prevent hyperamylasemia and pancreatitis after endoscopic retrograde cholangiopancreatography （PEP）.
METHODS： One hundred and seventy patients were enrolled and randomized to two groups： a study group （n = 85） who received 300 mg of oral allopurinol at 15 h and 3 h before endoscopic retrograde cholangiopancreatography （ERCP） and a control group （n = 85） receiving an oral placebo at the same times. Main Outcome Measurements included serum amylase levels and the number severity of the episodes of pancreatitis. Serum amylase levels were classified as normal （〈 150 IU/L） or hyperamylasemia （〉 151 IU/L）. Episodes of PEP were classified following Ranson＇s criteria and CT severity index.
RESULTS： Gender distribution was similar between groups. Mean age was 53.5 ±18.9 years for study group and 52.8 ± 19.8 years for controls. Also, the distribution of benign pathology was similar between groups. Hyperamylasemia was more common in the control group （P = 0.003）. Mild PEP developed in two patients from the study group （2.3%） and eight （9.4%） from control group （P = 0.04）, seven episodes were observed in high-risk patients of the control group （25%） and one in the allopurinol group （3.3%, P = 0.02）. Risk factors for PEP were precut sphincterotomy （P = 0.02）, pancreatic duct manipulation （P = 0.002） and multiple procedures （P = 0.000）. There were no deaths or side effects.
CONCLUSION： Oral allopurinol before ERCP decreased the incidences of hyperamylasemia and pancreatitis in patients submitted to high-risk procedures.     

ERCP术后急性胰腺炎并发症的危险因素及预防研究进展

内镜逆行性胰胆管造影(ERCP)以及相关治疗技术已成为胆胰疾病的重要治疗手段,ERCP 术后急性胰腺炎(AP)是常见且严重的并发症之一,目前研究发现．治疗性ERCP、Oddi括约肌运动功能障碍、Oddi括约肌压力检测、内镜下乳头括约肌气囊扩张术、插管困难与多次胰管注射、操作者的经验不足为ERCP术后急性胰腺炎的常见危险因素．关于预防ERCP 术后AP的药物研究被广泛开展,生长抑素和加贝酯被多数学者认为对AP有显著的预防作用．更广泛的药物研究其具体效果尚待进一步的研究证实．在内镜技术方面,选择性插管技术的改进、胰管支架和胆道引流技术被认为可有效地防止ERCP术后AP的发生．     

Risk of pancreatitis after endoscopic retrograde cholangiopancreatography and endoscopic biliary drainage

Background:

Pancreatitis is the most common and serious complication to occur after endoscopic retrograde cholangiopancreatography (ERCP). It is often associated with additional diagnostic modalities and/or treatment of obstructive jaundice. The aim of this study was to determine the risk of post-ERCP pancreatitis associated with pancreaticobiliary examination and endoscopic biliary drainage (EBD).

Methods:

A total of 740 consecutive ERCP procedures performed in 477 patients were analysed for the occurrence of pancreatitis. These included 470 EBD procedures and 167 procedures to further evaluate the pancreaticobiliary tract using brush cytology and/or biopsy, intraductal ultrasound and/or peroral cholangioscopy or peroral pancreatoscopy. The occurrence of post-ERCP pancreatitis was analysed retrospectively.

Results:

The overall incidence of post-ERCP pancreatitis was 3.9% (29 of 740 procedures). The risk factors for post-ERCP pancreatitis were: being female (6.5%; odds ratio [OR] 2.5, P= 0.02); first EBD procedure without endoscopic sphincterotomy (ES) (6.9%; OR 3.0, P= 0.003), and performing additional diagnostic procedures on the pancreatobiliary duct (9.6%; OR 4.6, P < 0.0001). Pancreatitis after subsequent draining procedures was rare (0.4%; OR for first-time drainage 16.6, P= 0.0003). Furthermore, pancreatitis was not recognized in 59 patients who underwent ES. Seven patients with post-EBD pancreatitis were treated with additional ES.

Conclusions:

Invasive diagnostic examinations of the pancreaticobiliary duct and first-time perampullary biliary drainage without ES were high-risk factors for post-ERCP pancreatitis. Endoscopic sphincterotomy may be of use to prevent post-EBD pancreatitis.     

治疗性内镜下逆行胰胆管造影术后急性胰腺炎高危因素分析

[目的]探索治疗性内镜下逆行胰胆管造影(endoscopic retrograde cholangiopancreatography,ERCP)术后急性胰腺炎(PEP)的高危因素与防治策略。[方法]运用单因素分析方法分析592例治疗性ERCP术后患者并发PEP的原因及防治措施。[结果]592例患者中,35例(5.9%)并发PEP,其中33例均为轻型胰腺炎,均经内科综合治疗后痊愈;2例为重症胰腺炎,1例治愈出院,1例死亡。与诱发PEP相关的高危因素有:女性,插管困难,既往有胰腺炎或胰腺癌,胰腺管显影或导丝插入胰管。[结论]治疗性ERCP发生PEP的因素不仅与患者自身临床因素有关,且与医师的操作技术有很大关系,改善患者身体条件、提高医师操作水平可减少PEP的发生。     

The role of endoscopic retrograde cholangiopancreatography in acute and chronic pancreatitis

Endoscopic retrograde cholangiopancreatography (ERCP) plays a pivotal role in the management of patients with acute and chronic pancreatitis. Whereas endoscopic observation during ERCP permits recognition of abnormalities involving the major and minor duodenal papillae such as papillary tumors or choledochocele, radiographic evaluation enables the detection of structural abnormalities of pancreaticobiliary ducts like strictures or calculi. Sphincter of Oddi manometry, a technical advance of ERCP, is essential for the diagnosis of sphincter of Oddi dysfunction, which may present clinically as recurrent pancreatitis. Because structural alterations of the pancreatic duct forms the hallmark of chronic pancreatitis, ERCP is highly sensitive and specific in diagnosing chronic pancreatitis. Apart from its diagnostic role, ERCP offers a variety of possibilities for therapeutic interventions in selected problems associated with pancreatitis. Endoscopic papillectomy and mucosal resection for tumors of the papilla, unroofing of a choledochocele, and sphincterotomy for sphincter ablation in sphincter of Oddi dysfunction are some of the therapeutic interventions possible during ERCP. Pancreatic ductal hypertension, which is considered to be the major pathophysiologic mechanism for disabling abdominal pain in chronic pancreatitis, also can be managed by ERCP-directed treatments. Pancreatic sphincterotomy, dilation of strictures, lithotripsy, extraction of calculi, and deployment of endoprosthesis constitute the commonly used therapeutic techniques in this situation. Besides offering a noninvasive alternative, these treatments are associated with a favorable clinical outcome comparable with that of operative treatments. Nevertheless, complications such as acute pancreatitis, bleeding, perforation, or sepsis may occur in 5% to 10% of patients undergoing these procedures. Therefore, careful selection of patients, appropriate preoperative care, and a team approach, including surgeon, interventional radiologist, and endoscopist, are important.     

Outcomes and timing of endoscopic retrograde cholangiopancreatography for acute biliary pancreatitis

BackgroundIndication of endoscopic retrograde cholangiopancreatography (ERCP) in acute biliary pancreatitis (ABP) is challenging.AimsIn this retrospective study, we analyzed real-world data to understand the ERCP practice in ABP in Hungarian centers.MethodsClinical data on ABP patients (2013–2015) were extracted from our large multicentric database. Outcomes, quality indicators and the role of early timing of ERCP (<24 h from admission) were analyzed.ResultsThere were 356 patients with ABP. ERCP was performed in 267 (75%). Performance indicators of ERCP proved to be suboptimal with a biliary cannulation rate of 84%. Successful vs unsuccessful cannulation of naïve papilla resulted in lower rates of local [22.9% vs 40.9%, (P = 0.012)] and systemic [4.9% vs 13.6%, (P = 0.042)] complications. Successful vs unsuccessful clearance resulted in lower rates of local complications [22.5% vs 40.8%, (P = 0.008)]. Successful cannulation and drainage correlated with less severe course of ABP [3.6% vs 15.9%, (P = 0.001) and 4.1% vs 12.2%, (P = 0.033)] respectively. A tendency of an increased rate of local complications was observed if ERCP was performed later [<24 h: 21.1% (35/166); between 24–48 h: 23.4% (11/47); >48h: 37.2% (16/43) (P = 0.088)].ConclusionOptimization of ERCP indication in ABP patients is critical as suboptimal ERCP practices in ABP without definitive stone detection are associated with poorer clinical outcomes.     

经内镜逆行胰胆管造影术后中重度胰腺炎的危险因素分析

探索中重度经内镜逆行胰胆管造影术后胰腺炎（post-endoscopic retrograde cholangiopancreatography pancreatitis, PEP）的相关危险因素。 方法：回顾性分析2010年6月——2020年6月期间在空军军医大学第一附属医院消化内科行经内镜逆行胰胆管造影术(endoscopic retrograde cholangiopancreatography, ERCP)的6 731例初始乳头胆胰疾病患者的临床资料。插管操作以及术后并发症相关参数均为前瞻性收集。主要研究终点为中重度PEP,通过Logistic回归分析中重度PEP的相关危险因素。 结果：6 731例初始乳头的ERCP患者总体PEP发生率为5.3%（n=359）,中重度PEP发生率为1.0%（n=68）。单因素分析显示女性、ERCP适应证、插管方式、插管时间、插管次数、误进胰管次数以及有无学员参与插管等因素与中重度PEP发生有关（P均<0.10）。多因素回归分析显示,女性（OR=2.32, 95%CI: 1.28~4.21, P=0.006）、非胆总管结石（OR=2.04, 95%CI: 1.16~3.59, P=0.014）、插管时间≥5 min(OR=2.23, 95%CI: 1.20~4.13, P=0.011)、误进胰管次数≥1次(OR=1.88, 95%CI: 1.03~3.44, P=0.040)和无学员参与插管（OR=1.81,95%CI: 1.02~3.22, P=0.043）是中重度PEP的独立危险因素。 结论：中重度PEP的独立危险因素包括女性、非胆总管结石、无学员参与的插管以及困难插管等。ERCP围手术期全程管理应重视对上述因素的评估。     

细胞因子与内镜逆行胰胆管造影术后胰腺炎关系的研究进展

内镜逆行胰胆管造影术(enoscopiC retrograde cholangiopancreatography,ERCP)是当前诊治肝、胆、胰疾病的重要手段之一.急性胰腺炎是ERCP术后最常见、最严重的并发症,目前其发病机制仍未完全阐明.近年来研究的普遍共识是炎性细胞因子在轻症胰腺炎向重症胰腺炎演进过程中发挥了重要作...     

Selective biliary cannulation techniques for endoscopic retrograde cholangiopancreatography procedures and prevention of post- endoscopic retrograde cholangiopancreatography pancreatitis

Numerous endoscopic retrograde cholangiopancreatography (ERCP) techniques have been reported to achieve selective biliary cannulation success. For standard biliary cannulation procedures, the wire-guided cannulation technique has been reported to reduce the rate of post-ERCP pancreatitis (PEP) and increase the biliary cannulation success rate, although conflicting reports exist. The pancreatic or double-guidewire technique and several precut techniques have been reported as useful techniques in difficult biliary cannulation cases. Although ERCP is a useful endoscopic procedure, the risk of adverse events, particularly post-ERCP pancreatitis, is inevitable. Previous studies and analyses have revealed the risk factors for PEP. The efficacy of prophylactic pancreatic duct stent placement and the administration of rectal nonsteroidal anti-inflammatory drugs for preventing PEP has also been reported. Herein, we reviewed reports in the literature regarding the current status of selective biliary cannulation techniques and PEP prevention.     

Pharmacologic prevention of pancreatitis after endoscopic retrograde cholangiopancreatography: Present and future

Despite extensive research over the past 2 decades, effective prevention of post–endoscopic retrograde cholangiopancreatography pancreatitis (PEP) using pharmacologic agents has been elusive. Recently, research that is focused on nonsteroidal anti-inflammatory drugs has provided renewed hope by demonstrating that a medication can indeed prevent PEP. Today, based on high-quality clinical trial data, rectal nonsteroidal anti-inflammatory drugs can be recommended for preventing PEP in high-risk cases,and given the highly favorable risk and cost-benefit ratios, they should be considered for all patients undergoing endoscopic retrograde cholangiopancreatography. Ongoing research will define the optimal dose of rectal indomethacin and whether this medication can eliminate the need for prophylactic pancreatic stent placement in high-risk cases. Additional research is necessary to define the role of other promising pharmacologic agents in clinical practice.