Effect of precut sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis:A systematic review and meta-analysis

AIM:To conduct a systemic review and meta-analysis to investigate the role of early precut technique.Multiple randomized controlled trails(RCTs)have reported conflicting results of the early precut sphincterotomy.METHODS:MEDLINE/PubMed,EMBASE,Cochrane Central Register of Controlled Trials and Database of Systematic Reviews,and recent abstracts from major conference proceedings were searched(June 2013).Randomized and non-randomized studies comparing early precut technique with prolonged standard methods were included.Pooled estimates of post-endoscopic retrograde cholangiopancreatography(ERCP)pancreatitis(PEP),cannulation and adverse events were analyzed by using odds ratio(OR).Random and fixed effects models were used as appropriate.Publication bias was assessed by funnel plots.Heterogeneity among studies was assessed by calculating I2 measure of inconsistency.RESULTS:Seven randomized and seven non-randomized trials met inclusion criteria.Meta-analysis of RCTs showed a decrease trend for PEP with early precut sphincterotomy but was not statistically significant(OR=0.58;95%CI:0.32-1.05;P=0.07).No heterogeneity was noted among the studies with I2 of 0%.CONCLUSION:Early precut technique for common bile duct cannulation decreases the trend of post-ERCP pancreatitis.     

Updated meta-analysis of pancreatic stent placement in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis

AIM: To investigate the efficacy and safety profile of pancreatic duct (PD) stent placement for prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).METHODS: We performed a search of MEDLINE, EMBASE, and Cochrane Library to identify randomized controlled clinical trials of prophylactic PD stent placement after ERCP. RevMan 5 software provided by Cochrane was used for the heterogeneity and efficacy analyses, and a meta-analysis was performed for the data that showed homogeneity. Categorical data are presented as relative risks and 95% confidence intervals (CIs), and measurement data are presented as weighted mean differences and 95%CIs.RESULTS: The incidence rates of severe pancreatitis, operation failure, complications and patient pain severity were analyzed. Data on pancreatitis incidence were reported in 14 of 15 trials. There was no significant heterogeneity between the trials (I² = 0%, P = 0.93). In the stent group, 49 of the 1233 patients suffered from PEP, compared to 133 of the 1277 patients in the no-stent group. The results of this meta-analysis indicate that it may be possible to prevent PEP by placing a PD stent.CONCLUSION: PD stent placement can reduce postoperative hyperamylasemia and might be an effective and safe option to prevent PEP if the operation indications are well controlled.     

乌司他丁在ERCP术后胰腺炎预防中的应用进展

内镜逆行胆胰管造影(endoscopic retrograde cholangio-pancreatography,ERCP)作为胆管及胰腺疾病的诊断、治疗手段已越来越多地应用于临床,同时,其术后并发症也日益受到重视。ERCP术后胰腺炎(post-ERCP pancreatitis,PEP)是其最常见也是最严重的并发症之一,术后胰腺炎的预防成为关注重点。作者根据国内外研究成果,对PEP的发病机制及危险因素进行阐述,并对乌司他丁(UTI)这一胰酶抑制剂的应用对PEP的预防效果及其应用的新进展作一综述。     

Antioxidant therapy in the management of acute, chronic and post-ERCP pancreatitis： A systematic review

We systematically reviewed the clinical trials which recruited antioxidants in the therapy of pancreatitis and evaluated whether antioxidants improve the outcome of patients with pancreatitis. Electronic bibliographic databases were searched for any studies which investigated the use of antioxidants in the management of acute pancreatitis （AP） or chronic pancreatitis （CP） and in the prevention of post-endoscopic retrograde cholangio-pancreatography （post-ERCP） pancreatitis （PEP） up to February 2009. Twenty-two randomized, placebo-controlled, clinical trials met our criteria and were included in the review. Except for a cocktail of antioxidants which showed improvement in outcomes in three different clinical trials, the results of the administration of other antioxidants in both AP and CP clinical trials were incongruent and heterogeneous.Furthermore, antioxidant therapy including allopurinol and N-acetylcysteine failed to prevent the onset of PEP in almost all trials. In conclusion, the present data do not support a benefit of antioxidant therapy alone or in combination with conventional therapy in the management of AP, CP or PER Further double blind, randomized, placebo-controlled clinical trials with large sample size need to be conducted.     

Prophecy about post-endoscopic retrograde cholangiopancreatography pancreatitis:From divination to science

One unresolved issue of endoscopic retrograde cholangiopancreatography(ERCP)is post-ERCP pancreatitis (PEP),which occurs in up to 40%of patients.Identification of risk factors for PEP is especially important in the field of ERCP practice because it may assist physicians in taking protective measures in situations with high risk.A decade ago,Freeman et al meticulously evaluated a large number of potentially relevant risk factors for PEP,which can be divided into patient-relat-ed and procedure-related issues.In this commentary, we summarize this classic article and reevaluate the risk factors for PEP from the current point of view.This is followed by assessment of strategies for prevention of PEP that can be divided into mechanical and pharmacologic methods.     

Usefulness of serum lipase for early diagnosis of post-endoscopic retrograde cholangiopancreatography pancreatitis

BACKGROUND Post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP)is new onset acute pancreatitis after ERCP. This complication is sometimes fatal.As such, PEP should be diagnosed early so that therapeutic interventions can be carried out. Serum lipase(s-Lip) is useful for diagnosing acute pancreatitis.However, its usefulness for diagnosing PEP has not been sufficiently investigated.AIM This study aimed to retrospectively examine the usefulness of s-Lip for the early diagnosis of PEP.METHODS We retrospectively examined 4192 patients who underwent ERCP at our two hospitals over the last 5 years. The primary outcomes were a comparison of the areas under the receiver operating characteristic(ROC) curves(AUCs) of s-Lip and serum amylase(s-Amy), s-Lip and s-Amy cutoff values based on the presence or absence of PEP in the early stage after ERCP via ROC curves, and the diagnostic properties [sensitivities, specificities, positive predictive values(PPV),and negative predictive value(NPV)] of these cutoff values for PEP diagnosis.RESULTS Based on the eligibility and exclusion criteria, 804 cases were registered. Over the entire course, PEP occurred in 78 patients(9.7%). It occurred in the early stage after ERCP in 40 patients(51.3%) and in the late stage after ERCP in 38 patients(48.7%). The AUCs were 0.908 for s-Lip [95% confidence interval(CI): 0.880-0.940,P 0.001] and 0.880 for s-Amy(95%CI: 0.846-0.915, P 0.001), indicating both are useful for early diagnosis. By comparing the AUCs, s-Lip was found to be significantly more useful for the early diagnosis of PEP than s-Amy(P = 0.023).The optimal cutoff values calculated from the ROC curves were 342 U/L for s-Lip(sensitivity, 0.859; specificity, 0.867; PPV, 0.405; NPV, 0.981) and 171 U/L for sAmy(sensitivity, 0.859; specificity, 0.763; PPV, 0.277; NPV, 0.979).CONCLUSION S-Lip was significantly more useful for the early diagnosis of PEP. Measuring sLip after ERCP could help diagnose PEP earlier; hence, therapeutic interventions can be provided earlier.     

Combination of two-hour post-endoscopic retrograde cholangiopancreatography amylase levels and cannulation times is useful for predicting post-endoscopic retrograde cholangiopancreatography pancreatitis

AIM To estimate the efficacy of 2 h post-endoscopic retrograde cholangiopancreatography(ERCP) serum amylase levels and other factors for predicting postERCP pancreatitis.METHODS This was a retrospective,single-center cohort study of consecutive patients who underwent ERCP from January 2010 to December 2013.Serum amylase levels were measured 2 h post-procedure,and patient- and procedure-related pancreatitis(PEP) risk factors wereanalyzed using a logistic model.RESULTS A total of 1520 cases(average age 72 ± 12 years,60% male) were initially enrolled in this study,and 1403 cases(725 patients) were ultimately analyzed after the exclusion of 117 cases.Fifty-five of these cases developed PEP.We established a 2 h serum amylase cutoff level of two times the upper limit of normal for predicting PEP.Multivariate analysis revealed that a cannulation time of more than 13 min [odds ratio(OR) 2.28,95%CI:1.132-4.651,P=0.0210] and 2 h amylase levels greater than the cutoff level(OR=24.1,95%CI:11.56-57.13,P0.0001) were significant predictive factors for PEP.Forty-seven of the 55 patients who developed PEP exhibited 2 h amylase levels greater than the cutoff level(85%),and six of the remaining eight patients who developed PEP(75%) required longer cannulation times.Only 2 of the 1403 patients(0.14%) who developed PEP did not exhibit concerning 2 h amylase levels or require longer cannulation times.CONCLUSION These findings indicate that the combination of 2 h post-ERCP serum amylase levels and cannulation times represents a valuable marker for identifying patients at high risk for PEP.     

Aggressive hydration with lactated ringer solution in prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: A systematic review and meta-analysis

Background:Acute pancreatitis is the most common complication of Endoscopic Retrograde Cholangiopancreatography (ERCP). There was no conclusion on the prevention of Post-ERCP Pancreatitis (PEP) by Lactated Ringer Solution.Aim:The purpose of this meta analyses is to determine whether aggressive hydration with Lactated Ringer Solution reduced the incidence of PEP.Methods:We retrieved randomized clinical trials comparing the preventive effects of aggressive hydration with Lactated Ringer Solution and standard hydration on PEP from PubMed, the Cochrane Library, Embase, the Web of Science, Clinical Trial.gov, Scopus database, CNKI, CQVIP and WanFang Data. Primary outcome was incidence of PEP. Secondary outcomes included incidence of hyperamylasemia, abdominal pain and adverse events.Results:Ten randomized controlled trials with 2200 patients were included in this meta-analysis. Meta-analysis showed that compared with standard hydration, aggressive hydration reduced the incidence of PEP (odds ratio [OR], 0.40; 95% confidence intervals [CI], 0.26–0.63; P < .0001). Compared with standard hydration, aggressive hydration also reduced the incidence of hyperamylasemia after ERCP (OR, 0.48; 95% CI, 0.38–0.60; P < .0001). There was significant difference between aggressive hydration and standard hydration in the incidence of abdominal pain (OR, 0.29; 95% CI, 0.11–0.73; P = .008). There was no difference in adverse events between aggressive hydration and standard hydration (OR, 0.93; 95% CI, 0.21–4.13; P = .93). Sensitivity analyses showed that neither alternative effect measures nor statistical models regarding heterogeneity affected the conclusions of this meta-analysis.Conclusion:Aggressive hydration with Lactated Ringer Solution during perioperative period of ERCP can prevent PEP.     

Current approaches and questions yet to be resolved for the prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis

Prophylaxis is important for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP), which is the most common and serious complication of ERCP. Although the current guidelines include independent patient- and procedure-related risk factors for PEP and available PEP prophylactic measures, the synergistic effect of these risk factors on PEP should also be considered, given that patients often harbor multiple risk factors. Furthermore, a combination of prophylactic measures is often selected in clinical practice. However, established methods estimating the synergistic effect of independent risk factors on PEP incidence are lacking, and evidence on the impact of combining prophylactic measures on PEP should be discussed. Selection of appropriate candidate patients for ERCP is also important to reduce the incidence of PEP associated with unnecessary ERCP. ERCP indications in patients with asymptomatic common bile duct stones (CBDSs) and in those with suspected CBDSs with no imaging-based evidence of stones are controversial. Further studies are warranted to predict the synergistic effect of independent risk factors on PEP, determine the best prophylactic PEP measures, and identify appropriate candidates for ERCP in patients with asymptomatic CBDSs and those with suspected CBDSs.     

Comparison between ulinastatin and nafamostat for prevention of post-endoscopic retrograde cholangiopancreatography complications: A prospective,randomized trial

ObjectivesPancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of this prospective trial was to compare the effect of ulinastatin and nafamostat on the prophylaxis of post-ERCP complications.MethodsA total of 159 patients who underwent ERCP were divided into ulinastatin (n = 53), nafamostat (n = 53) and control (n = 53) groups. Each patient received ulinastatin (150,000 units), nafamostat (20 mg), or placebo from 2-4 h before ERCP to 6–8 h after ERCP. The primary endpoint was the incidence of PEP, and the secondary endpoints were the incidence of post-ERCP hyperamylasemia, hyperlipasemia and abdominal pain.ResultsThe overall incidence of PEP was 6.3% (10/159) and no significant differences were observed between ulinastatin and nafamostat groups in terms of the incidences of PEP (1.9% and 3.8%, P = 0.560), hyperamylasemia, hyperlipasemia, and abdominal pain, although these were significantly lower than those of the control group (P < 0.001).ConclusionsThere was no significant difference for preventing PEP between ulinastatin and nafamostat and both drugs were efficacious for preventing post-ERCP complications.     

Pancreatic stents for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis should be inserted up to the pancreatic body or tail

AIM To investigate the location to which a pancreatic stent should be inserted to prevent post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP).METHODS Over a ten-year period at our hospital, 296 patients underwent their first ERCP procedure and had a pancreatic stent inserted; this study included 147 patients who had ERCP performed primarily for biliary investigation and had a pancreatic stent inserted to prevent PEP. We dividedthese patients into two groups: 131 patients with a stent inserted into the pancreatic head(head group) and 16 patients with a stent inserted up to the pancreatic body or tail(body/tail group). Patient characteristics and ERCP factors were compared between the groups.RESULTS Pancreatic amylase isoenzyme(p-AMY) levels in the head group were significantly higher than those in the body/tail group [138.5(7.0-2086) vs 78.5(5.0-1266.5), P = 0.03] [median(range)]. No cases of PEP were detected in the body/tail group [head group, 12(9.2%)]. Of the risk factors for post-ERCP hyperamylasemia(≥ p-AMY median, 131 IU/L), procedure time ≥ 60 min [odds ratio(OR) 2.65, 95%CI: 1.17-6.02, P = 0.02) and stent insertion into the pancreatic head(OR 3.80, 95%CI: 1.12-12.9, P = 0.03) were identified as independent risk factors by multivariate analysis.CONCLUSION Stent insertion up to the pancreatic body or tail reduces the risk of post-ERCP hyperamylasemia and may reduce the risk of PEP.     

Role of diclofenac in reducing post-endoscopic retrograde cholangiopancreatography pancreatitis

Background and Aims:  Acute pancreatitis following endoscopic retrograde cholangiography 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. Immediately after endoscopy, patients were given a suppository containing either 100 mg diclofenac or placebo. Estimation of serum amylase level and clinical evaluation were performed in all patients.
Results:  One hundred patients entered the trial, and 50 received rectal diclofenac. Fifteen patients developed pancreatitis (15%), of whom two received rectal diclofenac and 13 received placebo ( P  < 0.01).
Conclusions:  This trial shows that rectal diclofenac given immediately after endoscopic retrograde cholangiopancreatography can reduce the incidence of acute pancreatitis.     

Effect of somatostatin on prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis and hyperamylasemia: A systematic review and meta-analysis

Objective

To perform a meta-analysis of all available studies on the effect of prophylactic somatostatin administration on prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and post-ERCP hyperamylasemia (PEHA).

Somatostatin and gabexate for post-endoscopic retrograde cholangiopancreatography pancreatitis prevention: meta-analysis of randomized placebo-controlled trials

BACKGROUND AND AIM: Prior studies have suggested the efficacy of somatostatin and gabexate in post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis prevention. We examined this notion in our study. METHODS: An extensive literature search led to the inclusion of seven homogeneous high-quality studies (Jadad score >or=4), involving 3,130 patients. The studies were grouped according to the drug's length of administration: given as an infusion for 12 h (groups SOM1 and GAB1 for somatostatin and gabexate, respectively); given as an infusion for less then 12 h (groups SOM2 and GAB2 for somatostatin and gabexate, respectively); and given as a bolus (group SOM3 for somatostatin, none identified for gabexate). Separate meta-analyses investigating post-procedural pancreatitis and hyperamylasemia rates were conducted in a random effects model. RESULTS: Pancreatitis analyses yielded significant risk differences for the SOM1, SOM3 and GAB1 groups. The resulting values were 7.7% (95% confidence intervals [CI][3.4 to 12.0], P < 0.0001), 8.2% (95% CI [4.4 to 12.0], P < 0.0001) and 5.2% (95% CI [1.1 to 9.4], P = 0.01), respectively. No statistically significant risk differences were observed for the SOM2 and GAB2 groups: -2.3% (95% CI [-5.2 to 0.5], P = 0.11) and -1.1% (95% CI [-3.8 to 1.6], P = 0.41), respectively. Hyperamylasemia analyses yielded significant risk differences for the SOM1 and SOM3 groups (P = 0.017 and 0.001, respectively), although not for the SOM2, GAB1 and GAB2 groups (P = 0.44, 0.49 and 0.47, respectively). CONCLUSIONS: Somatostatin administered as a bolus seems to be an efficacious measure of post-ERCP pancreatitis prevention, reducing pancreatitis and hyperamylasemia rates, and being applicable to clinical practice. Further study is required before its introduction into routine care.     

Pancreatitis after endoscopic retrograde cholangiopancreatography: A narrative review

Acute post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is a feared and potentially fatal complication that can be as high as up to 30% in high-risk patients. Pre-examination measures, during the examination and after the examination are the key to technical and clinical success with a decrease in adverse events. Several studies have debated on the subject, however, numerous topics remain controversial, such as the effectiveness of prophylactic medications and the amylase dosage time. This review was designed to provide an update on the current scientific evidence regarding PEP available in the literature.     

Balloon dilation itself may not be a major determinant of post-endoscopic retrograde cholangiopancreatography pancreatitis

Endoscopic retrograde cholangiopancreatography(ERCP)is the essential first modality for common bile duct(CBD)stone therapy.The conventional endoscopic treatment for CBD stones is stone removal after endoscopic sphincterotomy(EST).Stone removal after papillary stretching using balloon dilation instead of the conventional method has been widely adopted.There are many reports regarding endoscopic papillary balloon dilation(EPBD)utilizing a small balloon(<10 mm)instead of EST for the removal of small CBD stones.In contrast,two cases of mortality due to postERCP pancreatitis(PEP)were reported after an EPBD clinical trial in the Western world,and the psychological barrier caused by these incidences hinders the use of this technique in Western countries.Endoscopic papillar large balloon dilation(EPLBD),which is used to treat large CBD stones,was not widely adopted when firstintroduced due to concerns about perforation and severe pancreatitis from the use of a large balloon(12-20mm).However,as experience with this procedure accumulates,the occurrence of PEP with EPLBD is confirmed to be much lower than with EPBD.This report reviews whether EPBD and EPLBD,two procedures that use balloon dilation but differ in terms of indications and concept,contribute to the occurrence of PEP.     

Comparison between ulinastatin and gabexate mesylate for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a prospective,randomized trial

Background It has been reported that the administration of ulinastatin, gabexate mesylate, or somatostatin may be effective in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, few randomized trials of ulinastatin and gabexate mesylate for the prevention of post-ERCP pancreatitis have been reported. The aim of this study was to compare the efficacy of ulinastatin and gabexate mesylate for the prevention of post-ERCP pancreatitis. Methods Sixty-eight patients who underwent diagnostic ERCP at our hospital were divided at random by computer-generated randomization into an ulinastatin group (n = 34) and a gabexate group (n = 34). Each patient received a continuous intravenous infusion of ulinastatin (150 000 units) or gabexate mesylate (600 mg), beginning 60–90 min before the ERCP and continuing until 22 h after the ERCP. The primary endpoint was the incidence of post-ERCP pancreatitis, and the secondary endpoints were the incidences of hyperenzymemia and pain. Results The overall incidence of post-ERCP pancreatitis was 2.9% (two patients), comprising one patient in the ulinastatin group and one patient in the gabexate group (2.9% vs 2.9%, respectively). Neither of these two patients developed severe pancreatitis. There were no significant differences in the serum levels of pancreatic enzymes or in the levels of pain between the two groups. Conclusions There was no clinical difference between the effect of preventive administration of ulinastatin and that of gabexate mesylate on the incidence of post-ERCP pancreatitis. Ulinastatin may be equivalent in efficacy to gabexate for reducing the incidence of post-ERCP pancreatitis.     

Placement of prophylactic pancreatic stents to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: A meta-analysis

AIM:To assess the effectiveness of pancreatic stents for preventing pancreatitis in high-risk patients after endoscopic retrograde cholangiopancreatography(ERCP).METHODS:PubMed,Embase,Science Citation Index,and Cochrane Controlled Trials Register were searched to identify relevant trials published in English.Inclu-sion and exclusion criteria were used to screen for suitable studies.Two reviewers independently judged the study eligibility while screening the citations.The methodological quality of the included trials was assessed using the Jadad scoring system.All results were expressed as OR and 95%CI.Data were analyzed using Stata12.0 software.RESULTS:Ten eligible randomized controlled trials were selected,including 1176 patients.A fixed-effects model in meta-analysis supported that pancreatic duct stents significantly decreased the incidence of postERCP pancreatitis(PEP)in high-risk patients(OR=0.25;95%CI:0.17-0.38;P<0.001).Pancreatic stents also alleviated the severity of PEP(mild pancreatitis after ERCP:OR=0.33;95%CI:0.21-0.54;P<0.001;moderate pancreatitis after ERCP:OR=0.30;95%CI:0.13-0.67;P=0.004).The result of severe pancreatitis after ERCP was handled more rigorously(OR=0.24;95%CI:0.05-1.16;P=0.077).Serum amylase levels were not different between patients with pancreatic stents and control patients(OR=1.08;95%CI:0.82-1.41;P=0.586).CONCLUSION:Placement of prophylactic pancreatic stents may lower the incidence of post-ERCP pancreatitis in high-risk patients and alleviate the severity of this condition.