External use of mirabilite to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in children:A multicenter randomized controlled trial

BACKGROUND Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography(ERCP).Currently,there is no suitable treatment for post-ERCP pancreatitis(PEP)prophylaxis.Few studies have prospectively evaluated interventions to prevent PEP in children.AIM To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children.METHODS This multicenter,randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria.Patients were randomly divided into the external use of mirabilite group(external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP)and blank group.The primary outcome was the incidence of PEP.The secondary outcomes included the severity of PEP,abdominal pain scores,levels of serum inflammatory markers[tumor necrosis factor-alpha(TNF-α)and serum interleukin-10(IL-10)],and intestinal barrier function markers[diamine oxidase(DAO),D-lactic acid,and endotoxin].Additionally,the side effects of topical mirabilite were investigated.RESULTSA total of 234 patients were enrolled,including 117 in the external use of mirabilite group and theother 117 in the blank group.The pre-procedure and procedure-related factors were notsignificantly different between the two groups.The incidence of PEP in the external use ofmirabilite group was significantly lower than that in the blank group(7.7%vs 26.5%,P<0.001).The severity of PEP decreased in the mirabilite group(P=0.023).At 24 h after the procedure,thevisual analog scale score in the external use of mirabilite group was lower than that in the blankgroup(P=0.001).Compared with those in the blank group,the TNF-αexpressions weresignificantly lower and the IL-10 expressions were significantly higher at 24 h after the procedurein the external use of mirabilite group(P=0.032 and P=0.011,respectively).There were nosignificant differences in serum DAO,D-lactic acid,and endotoxin levels before and after ERCPbetween the two groups.No adverse effects of mirabilite were observed.CONCLUSIONExternal use of mirabilite reduced the PEP occurrence.It significantly alleviated post-proceduralpain and reduced inflammatory response.Our results favor the external use of mirabilite toprevent PEP in children.

Best practices for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis

Acute pancreatitis is of one the most common gastroenterology-related indications for hospital admissions worldwide.With the widespread reliance on endoscopic retrograde cholangiopancreatography(ERCP)for the management of pancreaticobiliary conditions,post-ERCP pancreatitis(PEP)has come to represent an important etiology of acute pancreatitis.Despite many studies aiming to better understand the pathogenesis and prevention of this iatrogenic disorder,findings have been heterogeneous,and considerable variation in clinical practice exists.Herein,we review the literature regarding PEP with the goal to raise awareness of this entity,discuss recent data,and present evidence-based best practices.We believe this manuscript will be useful for gastrointestinal endoscopists as well as other specialists involved in the management of patients with 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.

Post-endoscopic retrograde cholangiopancreatography pancreatitis:A systematic review for prevention and treatment

BACKGROUND Post endoscopic retrograde cholangiopancreatography (ERCP) is comparatively complex application. Researchers has been investigated prevention of post-ERCP pancreatitis (PEP), since it has been considered to be the most common complication of ERCP. Although ERCP can lead various complications, it can also be avoided. AIM To study the published evidence and systematically review the literature on the prevention and treatment for PEP. METHODS A systematic literature review on the prevention of PEP was conducted using the electronic databases of ISI Web of Science, PubMed and Cochrane Library for relevant articles. The electronic search for the review was performed by using the search terms “Post endoscopic retrograde cholangiopancreatography pancreatitis” AND “prevention” through different criteria. The search was restricted to randomized controlled trials (RCTs) performed between January 2009 and February 2019. Duplicate studies were detected by using EndNote and deleted by the author. PRISMA checklist and flow diagram were adopted for evaluation and reporting. The reference lists of the selected papers were also scanned to find other relevant studies. RESULTS 726 studies meeting the search criteria and 4 relevant articles found in the edited books about ERCP were identified. Duplicates and irrelevant studies were excluded by screening titles and abstracts and assessing full texts. 54 studies were evaluated for full text review. Prevention methods were categorized into three groups as (1) assessment of patient related factors;(2) pharmacoprevention;and (3) procedural techniques for prevention. Most of studies in the literature showed that young age, female gender, absence of chronic pancreatitis, suspected Sphincter of Oddi dysfunction, recurrent pancreatitis and history of previous PEP played a crucial role in posing high risks for PEP. 37 studies designed to assess the impact of 24 different pharmacologic agents to reduce the development of PEP delivered through various administration methods were reviewed. Nonsteroidal anti-inflammatory drugs are widely used to reduce risks for PEP. Rectal administration of indomethacin immediately prior to or after ERCP in all patients is recommended by European Society for Gastrointestinal Endoscopy guidelines to prevent the development of PEP. The majority of the studies reviewed revealed that rectally administered indomethacin had efficacy to prevent PEP. Results of the other studies on the other pharmacological interventions had both controversial and promising results. Thirteen studies conducted to evaluate the efficacy of 4 distinct procedural techniques to prevent the development of PEP were reviewed. Pancreatic Stent Placement has been frequently used in this sense and has potent and promising benefits in the prevention of PEP. Studies on the other procedural techniques have had inconsistent results. CONCLUSION Prevention of PEP involves multifactorial aspects, including assessment of patients with high risk factors for alternative therapeutic and diagnostic techniques, administration of pharmacological agents and procedural techniques with highly precise results in the literature.

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.

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.

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

AIM: To investigate the efficacy and safety profile ofpancreatic 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. Rev Man 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.

Systematic review and meta-analysis on the prophylactic role of non-steroidal anti-inflammatory drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis

AIM: To critically appraise the published randomized, controlled trials on the prophylactic effectiveness of the non-steroidal anti-inflammatory drugs(NSAIDs), in reducing the risk of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis. METHODS: A systematic literature search(MEDLINE, Embase and the Cochrane Library, from inception of the databases until May 2015) was conducted to identify randomized, clinical trials investigating the role of NSAIDs in reducing the risk of post-ERCP pancreatitis. Random effects model of the meta-analysis was carried out, and results were presented as odds ratios(OR) with corresponding 95%CI.RESULTS: Thirteen randomized controlled trials on 3378 patients were included in the final meta-analysis. There were 1718 patients in the NSAIDs group and 1660 patients in non-NSAIDs group undergoing ERCP. The use of NSAIDs(through rectal route or intramuscular route) was associated with the reduced risk of post-ERCP pancreatitis [OR, 0.52(0.38-0.72), P = 0.0001]. The use of pre-procedure NSAIDs was effective in reducing approximately 48% incidence of post-ERCP pancreatitis, number needed to treat were 16 with absolute risk reduction of 0.05. But the risk of post-ERCP pancreattis was reduced by 55% if NSAIDs were administered after procedure. Similarly, diclofenac was more effective(55%) prophylactic agent compared to indomethacin(41%).CONCLUSION: NSAIDs seem to have clinically proven advantage of reducing the risk of post-ERCP pancreatitis.

Antioxidant therapy in acute,chronic and post-endoscopic retrograde cholangiopancreatography pancreatitis:An updated systematic review and meta-analysis

AIM:To investigate the efficacy and adverse effects of antioxidant therapy in acute pancreatitis(AP),chronic pancreatitis(CP) and post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP).METHODS:Pub Med,Scopus,Google Scholar,Cochrane library database,and Evidence-based medicine/clinical trials published before August 2014 were searched. Clinical and laboratory outcomes of randomized trials of antioxidant therapy in patients with AP,CP and PEP were included. The methodological quality of the trials was assessed by the Jadad score based on the description of randomization,blinding,and dropouts(withdrawals). The results of the studies were pooled and meta-analyzed to provide estimates of the efficacy of antioxidant therapy.RESULTS:Thirty four trials out of 1069 potentially relevant studies with data for 4898 patients wereeligible for inclusion. Antioxidant therapy significantly reduced the length of hospital stay in AP patients {mean difference-2.59 d(95%CI:-4.25-(-0.93)],P = 0.002}. Although,antioxidant therapy had no significant effect on serum C reactive protein(CRP) after 5-7 d in AP patients [mean difference-9.57(95%CI:-40.61-21.48,P = 0.55],it significantly reduced serum CRP after 10 d {mean difference-45.16 [95%CI:-89.99-(-0.33)],P = 0.048}. In addition,antioxidant therapy had no significant effect on CP-induced pain [mean difference-2.13(95%CI:-5.87-1.6),P = 0.26]. Antioxidant therapy had no significant effects on the incidence of all types of PEP [mean difference 1.05(95%CI:0.74-1.5),P = 0.78],severe PEP [mean difference 0.92(95%CI:0.43-1.97),P = 0.83],moderate PEP [mean difference 0.82(95%CI:0.54-1.23),P = 0.33],and mild PEP [mean difference 1.33(95%CI:0.99-1.78),P = 0.06]. Furthermore,while antioxidant therapy had no significant effect on serum amylase after less than 8 h sampling [mean difference-20.61(95%CI:-143.61-102.39),P = 0.74],it significantly reduced serum amylase close to 24-h sampling {mean difference-16.13 [95%CI:-22.98-(-9.28)],P < 0.0001}.CONCLUSION:While there is some evidence to support antioxidant therapy in AP,its effect on CP and PEP is still controversial.

Suppository naproxen reduces incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis: Randomized controlled trial

AIM: To determine the efficacy of rectally administered naproxen for the prevention of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP).METHODS: This double-blind randomized control trial conducted from January 2013 to April 2014 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 324 patients were selected from candidates for diagnostic or therapeutic ERCP by using the simple sampling method. Patients received a single dose of Naproxen(500 mg; n = 162) or a placebo(n = 162) per rectum immediately before ERCP. The overall incidence of PEP, incidence of mild to severe PEP, serum amylase levels and adverse effects were measured. The primary outcome measure was the development of pancreatitis onset of pain in the upper abdomen and elevation of the serum amylase level to > 3 × the upper normal limit(60-100 IU/L) within 24 h after ERCP. The severity of PEP was classified according to the duration of therapeutic intervention for PEP: mild, 2-3 d; moderate 4-10 d; and severe, > 10 d and/or necessitated surgical or intensive treatment, or contributed to death.RESULTS:PEP occurred in 12 %(40/324) o f participants, and was significantly more frequent in the placebo group compared to the naproxen group(P < 0.01). Of the participants, 25.9%(84/324) developed hyperamylasemia within 2 h of procedure completion, among whom only 35 cases belonged to the naproxen group(P < 0.01). The incidence of PEP was significantly higher in female sex, in patients receiving pancreatic duct injection, more than 3 times pancreatic duct cannulations, and ERCP duration more than 40 min(P s < 0.01). There were no statistically significant differences between the groups regarding the procedures or factors that might increase the risk of PEP, sphincterotomy, precut requirement, biliary duct injection and number of pancreatic duct cannulations. In the subgroup of patients with pancreatic duct injection, the rate of pancreatitis in the naproxen group was significantly lower than that in the placebo(6 patients vs 23 patients, P < 0.01, RRR = 12%, AR = 0.3, 95%CI: 0.2-0.6). Naproxen reduced the PEP in patients with ≥ 3 pancreatic cannulations(P < 0.01, RRR = 25%, AR = 0.1, 95%CI: 0.1-0.4) and an ERCP duration > 40 min(P < 0.01, RRR = 20%, AR = 0.9, 95%CI: 0.4-1.2).CONCLUSION: Single dose of suppository naproxen administered immediately before ERCP reduces the incidence of PEP.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis by pancreatic duct stenting using a loop-tipped guidewire

AIM: To examine whether it is possible to prevent the occurrence of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis in patients experiencing difficulties with selective biliary duct cannulation by pancreatic duct stenting using a looptipped guidewire.METHODS: Procedure success rate, frequency of unintended insertion of the guidewire into side branches of the pancreatic duct, and incidence of procedural accidents were examined using a loop-tipped guidewire(Group A, 20 patients), and a conventional straighttype guidewire(Group B, 20 patients).RESULTS: The success rate of the procedure was 100% in both groups. Unintended insertion of the guidewire into a side branch of the pancreatic duct occurred 0.056 ± 0.23(0-1) times in Group A and 2.3 ±1.84(0-5) times in Group B; thus, unintended insertion of the guidewire into a side branch of the pancreatic duct was seen significantly less frequently in Group A. There were no procedural accidents in Group A, whereas pancreatitis occurred in one Group B patient; however, the difference between the two groups was not statistically significant. The serum amylase level after ERCP was 257.15 ± 136.4(88-628) IU/L in Group A, and 552.05 ± 534.57(101-2389) IU/L in Group B, showing a significantly lower value in Group A. Hyperamylasemia was found in two patients(10%) in Group A, and nine(45%) in Group B, showing a significantly lower value in Group A.CONCLUSION: The results suggest that in patients who experience difficulties with biliary cannulation, the use of a loop-tipped guidewire for pancreatic duct stenting may assist with the prevention of post-ERCP pancreatitis, and thereby to a reduction of the risk of post-ERCP pancreatitis or hyperamylasemia.

Risk factors for the development of post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with asymptomatic common bile duct stones

BACKGROUND Previous studies have revealed that patients with asymptomatic common bile duct(CBD)stones are at a high risk of developing post-endoscopic retrograde cholangiopancreatography(ERCP)pancreatitis(PEP).However,no studies to date have addressed the risk factors for PEP in patients with asymptomatic CBD stones.AIM To examine the risk factors for PEP in patients with asymptomatic CBD stones.METHODS Using medical records of three institutions in Japan for 6 years,we identified a total of 1135 patients with choledocholithiasis including 967 symptomatic patients and 168 asymptomatic patients with native papilla who underwent therapeutic ERCP.We performed univariate and multivariate analyses to examine the risk factors for PEP in the 168 patients with asymptomatic CBD stones.RESULTS The overall incidence rate of PEP in all the patients with during study period was 4.7%(53/1135).Of the 168 patients with asymptomatic CBD stones,24(14.3%)developed PEP.In univariate analysis,precut sphincterotomy(P=0.009)and biliary balloon sphincter dilation(P=0.043)were significant risk factors for PEP.In multivariate analysis,precut sphincterotomy(P=0.002,95%CI:2.2-27.8,odds ratio=7.7),biliary balloon sphincter dilation(P=0.015,95%CI:1.4-17.3,odds ratio=4.9),and trainee endoscopists(P=0.048,95%CI:1.01-8.1,odds ratio=2.9)were significant risk factors for PEP.CONCLUSION ERCP for asymptomatic CBD stones should be performed by experienced endoscopists.When performing precut sphincterotomy or biliary balloon sphincter dilation in patients with asymptomatic CBD stones,the placement of a prophylactic pancreatic stent is strongly recommended to prevent PEP.

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,P<0.0001) 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.

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 s-Amy(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 s-Lip after ERCP could help diagnose PEP earlier;hence,therapeutic interventions can be provided earlier.

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.

Antioxidant drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis:What does evidence suggest?

AIM:To determine whether or not the use of antioxidant supplementation aids in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis.METHODS:A systematic review of randomized controlled trials(RCTs) was made to evaluate the preventive effect of prophylactic antioxidant supplementation in post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP).The inclusion criteria included:acute post-endoscopic retrograde cholangiopancreatography pancreatitis in adults; randomized clinical trials with the use of any antioxidant as an intervention compared with placebo,to reduce PEP.The outcome measure was the incidence and severity of PEP.Twelve RCTs involving 3110 patients since 1999 wereincluded.The antioxidants used were selenite,β-carotene,and pentoxifylline(each one in one trial),N-acetylcysteine(NAC) in three trials,and allopurinol in six trials.The group of patients treated with NAC received different doses; either oral or intravenous,and allopurinol-treated patients received five different oral doses in two different administration periods.The results are expressed with raw numbers,proportions,as well as mean and standard deviations.The incidence of pancreatitis between groups was analyzed with Pearson's χ2 test or Fisher's exact test(F).The main outcome is expressed as relative risks and 95%CI.RESULTS:The incidence of pancreatitis in all antioxidant treatment groups was 8.6%,whereas it was 9.7% in the control group.The antioxidants used were selenite,β-carotene,and pentoxifylline(each one in one trial),NAC in three trials,and allopurinol in six trials.In allopurinol trials,three different dosifications were used; two trials reported a low dosage(of less than 400 mg),two trials reported a moderate dose(600 mg) and the remaining two employed higher doses(more than 900 mg).Supplementation was not associated with a significant reduction in the incidence of PEP [relative risk(RR) = 0.93; 95%CI:0.82-1.06; P = 0.28].In addition,the incidences of PEP in patients treated with allopurinol and those treated with other antioxidants were similar to that observed in patients who received the placebo(RR for trials with allopurinol,0.92; 95%CI:0.78-1.08; P = 0.31) and,with the use of other antioxidants,the incidence of PEP was 8.9%,whereas it was 9.7% in the control group(RR = 0.95; 95%CI:0.77-1.18; P = 0.19).CONCLUSION:Antioxidant supplementation shows no beneficial effect on the incidence of PEP.There is a lack of robust trials to support the use of antioxidants for prevention.

Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis?

AIM:To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography(ERCP)pancreatitis and hyperamylasaemia in a multicentre study.METHODS:A prospective,randomised,placebocontrolled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin,or an inert placebo,10-15 min before ERCP.Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters,and computed tomography/magnetic resonance imaging findings if required.RESULTS:Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation.The results of 665 investigations were evaluated:347 in the indomethacin group and 318 in the placebo group.The distributions of the risk factors in the two groups did not differ significantly.Pancreatitis developed in 42 patients(6.3%):it was mild in34(5.1%)and severe in eight(1.2%)cases.Hyperamylaesemia occurred in 160 patients(24.1%).There was no significant difference between the indomethacin and placebo groups in the incidence of either postERCP pancreatitis(5.8%vs 6.9%)or hyperamylasaemia(23.3%vs 24.8%).Similarly,subgroup analysis did not reveal any significant differences between the two groups.CONCLUSION:100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis.

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.

Prophylactic effect of glyceryl trinitrate on post-endoscopic retrograde cholangiopancreatography pancreatitis:A randomized placebo-controlled trial

AIM:To examine the prophylactic effect of glyceryl trinitrate on post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis and hyperamylasemia.METHODS:Patients scheduled for ERCP were randomly divided into study group and placebo group.Patients in study group and placebo group were treated with 5 mg glyceryl trinitrate and 100 mg vitamin C,respectively,5 min before endoscopic maneuvers.RESULTS:A total of 74 patients were enrolled in the final analysis.Post-ERCP pancreatitis occurred in 3 patients(7.9%) of the study group and 9 patients(25%) in the placebo group(P = 0.012).Hyperamylasemia occurred in 8 patients of the study group(21.1%) and 13 patients(36.1%) of the placebo group(P = 0.037).CONCLUSION:Glyceryl trinitrate before ERCP can effectively prevent post-ERCP and hyperamylasemia.

Post-endoscopic retrograde cholangiopancreatography pancreatitis: Risk factors and predictors of severity

AIM To detect risk factors for post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP) and investigate the predictors of its severity.METHODS This is a prospective cohort study of all patients who underwent ERCP.Pre-ERCP data,intraoperative data,and post-ERCP data were collected.RESULTS The study population consisted of 996 patients.Their mean age at presentation was 58.42(± 14.72) years,and there were 454 male and 442 female patients.Overall,PEP occurred in 102(10.2%) patients of the study population; eighty(78.4%) cases were of mild to moderate degree,while severe pancreatitis occurred in 22(21.6%) patients.No hospital mortality was reported for any of PEP patients during the study duration.Age less than 35 years(P = 0.001,OR = 0.035),narrower common bile duct(CBD) diameter(P = 0.0001) and increased number of pancreatic cannulations(P = 0.0001) were independent risk factors for the occurrence of PEP.CONCLUSION PEP is the most frequent and devastating complication after ERCP.Age less than 35 years,narrower median CBD diameter and increased number of pancreaticcannulations are independent risk factors for the occurrence of PEP.Patients with these risk factors are candidates for prophylactic and preventive measures against PEP.