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, placebo-controlled 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 in 34 (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 post-ERCP 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.
Endoscopic retrograde cholangiopancreatography; Post-endoscopic retrograde cholangiopancreatography pancreatitis; Hyperamylasaemia; Non-steroidal anti-inflammatory drugs; Indomethacin
Post-procedure pancreatitis is the most common complication of endoscopic retrograde cholangio pancreatography (ERCP) and carries a high morbidity and mortality occurring in at least 3%-5% of all procedures. We reviewed the available literature searching for “ERCP” and “pancreatitis” and “post-ERCP pancreatitis”. in PubMed and Medline. This review looks at the diagnosis, risk factors, causes and methods of preventing post-procedure pancreatitis. These include the evidence for patient selection, endoscopic techniques and pharmacological prophylaxis of ERCP induced pancreatitis. Selecting the right patient for the procedure by a risk benefits assessment is the best way of avoiding unnecessary ERCPs. Risk is particularly high in young women with sphincter of Oddi dysfunction (SOD). Many of the trials reviewed have rather few numbers of subjects and hence difficult to appraise. Meta-analyses have helped screen for promising modalities of prophylaxis. At present, evidence is emerging that pancreatic stenting of patients with SOD and rectally administered nonsteroidal anti-inflammatory drugs in a large unselected trial reduce the risk of post-procedure pancreatitis. A recent meta-analysis have demonstrated that rectally administered indomethecin, just before or after ERCP is associated with significantly lower rate of pancreatitis compared with placebo [OR = 0.49 (0.34-0.71); P = 0.0002]. Number needed to treat was 20. It is likely that one of these prophylactic measures will begin to be increasingly practised in high risk groups.
Acute pancreatitis; Endoscopic retrograde cholangio pancreatography
AIM: To determine the effectiveness of pancreatic duct (PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high risk patients.
METHODS: Authors conducted a single-blind, randomized controlled trial to evaluate the effectiveness of a pancreatic spontaneous dislodgement stent against post-ERCP pancreatitis, including rates of spontaneous dislodgement and complications. Authors defined high risk patients as having any of the following: sphincter of Oddi dysfunction, difficult cannulation, prior history of post-ERCP pancreatitis, pre-cut sphincterotomy, pancreatic ductal biopsy, pancreatic sphincterotomy, intraductal ultrasonography, or a procedure time of more than 30 min. Patients were randomized to a stent group (n = 60) or to a non-stent group (n = 60). An abdominal radiograph was obtained daily to assess spontaneous stent dislodgement. Post-ERCP pancreatitis was diagnosed according to consensus criteria.
RESULTS: The mean age (± standard deviation) was 67.4 ± 13.8 years and the male: female ratio was 68:52. In the stent group, the mean age was 66 ± 13 years and the male: female ratio was 33:27, and in the non-stent group, the mean age was 68 ± 14 years and the male: female ratio was 35:25. There were no significant differences between groups with respect to age, gender, final diagnosis, or type of endoscopic intervention. The frequency of post-ERCP pancreatitis in PD stent and non-stent groups was 1.7% (1/60) and 13.3% (8/60), respectively. The severity of pancreatitis was mild in all cases. The frequency of post-ERCP pancreatitis in the stent group was significantly lower than in the non-stent group (P = 0.032, Fisher’s exact test). The rate of hyperamylasemia were 30% (18/60) and 38.3% (23 of 60) in the stent and non-stent groups, respectively (P = 0.05, χ2 test). The placement of a PD stent was successful in all 60 patients. The rate of spontaneous dislodgement by the third day was 96.7% (58/60), and the median (range) time to dislodgement was 2.1 (2-3) d. The rates of stent migration, hemorrhage, perforation, infection (cholangitis or cholecystitis) or other complicationss were 0% (0/60), 0% (0/60), 0% (0/60), 0% (0/60), 0% (0/60), respectively, in the stent group. Univariate analysis revealed no significant differences in high risk factors between the two groups. The pancreatic spontaneous dislodgement stent safely prevented post-ERCP pancreatitis in high risk patients.
CONCLUSION: Pancreatic stent placement is a safe and effective technique to prevent post-ERCP pancreatitis. Therefore authors recommend pancreatic stent placement after ERCP in high risk patients.
Endoscopic retrograde cholangiopancreatography; Pancreatitis; Postoperative complications; Prophylaxis; Stents
A recent large-scale randomized controlled trial (RCT) demonstrated
that rectal indomethacin administration is effective in addition to
pancreatic stent placement (PSP) for preventing post-endoscopic retrograde
cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We
performed a post hoc analysis of this RCT to explore
whether rectal indomethacin can replace PSP in the prevention of PEP and to
estimate the potential cost savings of such an approach.
We retrospectively classified RCT subjects into four prevention
groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone,
and (4) the combination of PSP and indomethacin. Multivariable logistic
regression was used to adjust for imbalances in the prevalence of risk
factors for PEP between the groups. Based on these adjusted PEP rates, we
conducted an economic analysis comparing the costs associated with PEP
prevention strategies employing rectal indomethacin alone, PSP alone, or the
combination of both.
After adjusting for risk using two different logistic regression
models, rectal indomethacin alone appeared to be more effective for
preventing PEP than no prophylaxis, PSP alone, and the combination of
indomethacin and PSP. Economic analysis revealed that indomethacin alone was
a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy
employing rectal indomethacin alone could save approximately $150 million
annually in the United States compared with a strategy of PSP alone, and $85
million compared with a strategy of indomethacin and PSP.
This hypothesis-generating study suggests that prophylactic rectal
indomethacin could replace PSP in patients undergoing high-risk ERCP,
potentially improving clinical outcomes and reducing healthcare costs. A RCT
comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be efficacious to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the target patients, the type of NSAID, the route of administration and the time of drug delivery remain unclear, as well as the potential efficacy in reducing the severity of pancreatitis, length of hospital stay and mortality. The objective of the study was to evaluate these questions by performing a systematic review and meta-analysis.
Multiple searches were performed in the main databases. Randomized controlled trials (RCTs) comparing NSAIDs vs. placebo in the prevention of post-ERCP pancreatitis were included. Primary endpoint of the study was the efficacy for pancreatitis prevention. Sub-analyses were performed to determine the risk reduction in high and low risk patients, and to define optimal time, route of administration, and type of NSAID. Secondary endpoints were safety, moderate to severe pancreatitis prevention and reduction of hospital stay and mortality.
Nine RCTs enrolling 2133 patients were included. The risk of pancreatitis was lower in the NSAID group than in the placebo group (RR 0.51; 95%CI 0.39–0.66). The number needed to treat was 14. The risk of moderate to severe pancreatitis was also lower in the NSAID group. (RR 0.46; 95%CI 0.28–0.76). No adverse events related to NSAID use were reported. NSAIDs were effective in both high-risk and unselected patients (RR 0.53; 95%CI 0.30–0.93 and RR 0.57; 95%CI 0.37–0.88). In the subanalyses, only rectal administration of either indomethacin (RR 0.54; 95%CI 0.38–0.75) or diclofenac (RR 0.42; 95%CI 0.21–0.84) was shown to be effective. There were not enough data to perform a meta-analysis in hospital stay reduction. No deaths occurred.
A single rectal dose of indomethacin or diclofenac before or immediately after ERCP is safe and prevents procedure-related pancreatitis both in high risk and in unselected patients.
Acute pancreatitis remains the most frequent complication of endoscopic retrograde cholangiopancreatography (ERCP), with reported incidence rates that have changed little over several decades. Patient- and procedure-related risk factors for post-ERCP pancreatitis (PEP) are well-defined. Effective measures to prevent PEP have been identified, including improvements in cannulation techniques and pancreatic stenting, as well as pharmacological intervention. Pharmacotherapy has been widely studied in the prevention of PEP, but the effect in averting PEP has been inconclusive. Although pharmacological prophylaxis is appealing, attempts to find an ideal drug are incomplete. Most available data on the efficacy of pharmacological agents for PEP prophylaxis have been obtained from patients at average risk for PEP. However, recently, a randomized prospective controlled trial of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent PEP in high-risk patients was published. The results revealed that rectal indomethacin reduced the incidence of PEP significantly. Thus, rectal administration of diclofenac or indomethacin immediately before or after ERCP is used routinely to prevent PEP. However, additional studies with NSAIDs using large numbers of subjects are necessary to confirm the prophylactic effect of these drugs and to establish whether they act synergistically with other prophylactic interventions, including pancreatic stenting.
Pancreatitis; Cholangiopancreatography, endoscopic retrograde; Anti-inflammatory agents, non-steroidal; Prevention and control
Introduction. Endoscopic retrograde cholangiopancreatography (ERCP) is a complex endoscopic technique that evolved from a diagnostic to a mainly therapeutic procedure. This was due to the identification of post-procedural complications that can follow both simple ERCP and that associated with the instrumentation of the biliary and pancreatic ductals. The identification of post ERCP complications in a proportion of 5 to 10% of cases, with a mortality rate of 0.33%, imposed their analysis and study of risk factors involved in their occurrence. The significance of post ERCP complications reveals the necessity of their avoidance by adopting additional measures if risk factors are identified.
Materials and methods. We have retrospectively analyzed 900 cases that underwent ERCP in the Surgery Department of "Sf. Ioan" Clinical Hospital in a period of 17 years. The complications of the procedure were studied. Among them, a special attention was given to post-ERCP acute pancreatitis (pERCP-AP), the most common complication that occurred in the study group. We also tried to find out and highlight the risk factors for this complication.
Results. ERCP is a relatively safe invasive procedure, yet it has complications (8% of cases), some of them potentially fatal (mortality 0.43%). The most common complications after ERCP are acute pancreatitis (3.7%), papillary bleeding (1.04%), retroperitoneal duodenal perforation (0.69%) and biliary septic complications like acute cholecystitis and cholangitis (1.21%). Acute pancreatitis is by far the most common complication. Risk factors for its occurrence are difficult sphincterotomy with precut use, failure of CBD desobstruction, pancreatic sphincterotomy, repeated injection of contrast in the pancreatic ductal system, dysfunction of the sphincter of Oddi and the absence of changes of chronic pancreatitis. When risk factors are identified, the patients’ selection must be very strict and diagnostic ERCP should be avoided in favor of non-invasive diagnostic methods (MRI-cholangiography, echo-endoscopy).
ERCP; post ERCP complications; post ERCP acute pancreatitis; risk factors
Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangio-pancreatography (ERCP) and its incidence may exceed 25% in some high-risk patient subsets. In some patients, pancreatitis may follow a severe course with pancreatic necrosis, multiorgan failure, permanent disability and even death. Hence, approaches which minimize both the incidence and severity of post-ERCP pancreatitis are worth pursuing. Pancreatic stents have been used with some success in the prevention of post-ERCP, while so far pharmacological trials have yielded disappointing results. A recent multicenter, randomized, placebo-controlled, double-blind trial has shown that rectally administered indomethacin is effective in reducing the incidence of post-ERCP pancreatitis, the occurrence of episodes of moderate-to-severe pancreatitis and the length of hospital stay in high-risk patients. These results together with the demonstration that rectal administration of indomethacin is not associated with enhanced risk of bleeding strongly support the use of this drug in the prophylaxis of post-ERCP pancreatitis.
Endoscopic retrograde cholangiopancreatography; Post-endoscopic retrograde cholangiopancreatography pancreatitis; Non-steroidal anti-inflammatory drugs; Indomethacin; Pancreatitis prevention
Somatostatin has been extensively studied for the prophylaxis of pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, the results remain controversial. The present retrospective cohort study aimed to investigate the efficacy of pre- and post-ERCP somatostatin administration in the prevention of post-ERCP pancreatitis (PEP). All ERCP procedures performed at one hospital between January 2009 and December 2012 were reviewed. They were divided into three groups based on somatostatin administration: pre-ERCP som group (somatostatin administration: 0.25 mg/h for 24 h, starting 1 h prior to ERCP), post-ERCP som group (somatostatin administration: 0.25 mg/h for 24 h, starting immediately following ERCP), and control group (no somatostatin administration). Out of a total of 304 cases, 81 received pre-ERCP somatostatin; 126 received post-ERCP somatostatin and 97 were not administered somatostatin. Pre-ERCP somatostatin was effective in reducing the incidence of PEP compared with that in the control group (4.9 vs. 16.5%; P=0.017). This benefit was significant in high-risk patients (8.9 vs. 26.0%; P=0.035), but not in low-risk patients (0 vs. 6.4%; P=0.254). Post-ERCP somatostatin was not effective in preventing PEP in high- or low-risk patients. In conclusion, pre-ERCP somatostatin may be effective in reducing the risk of PEP in high-risk patients, but not in low-risk patients. Post-ERCP somatostatin did not reveal a benefit in high- or low-risk patients. However, large randomized controlled trials are required to further confirm these findings.
post-endoscopic retrograde cholangiopancreatography pancreatitis; somatostatin; retrospective study; prevention
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 μg 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.
endoscopic retrograde cholangiopancreatography; pancreatitis; somatostatin
AIM: To address endoscopic outcomes of post-Orthotopic liver transplantation (OLT) patients diagnosed with a “redundant bile duct” (RBD).
METHODS: Medical records of patients who underwent OLT at the Liver Transplant Center, University Texas Health Science Center at San Antonio Texas were retrospectively analyzed. Patients with suspected biliary tract complications (BTC) underwent endoscopic retrograde cholangiopancreatography (ERCP). All ERCP were performed by experienced biliary endoscopist. RBD was defined as a looped, sigmoid-shaped bile duct on cholangiogram with associated cholestatic liver biomarkers. Patients with biliary T-tube placement, biliary anastomotic strictures, bile leaks, bile-duct stones-sludge and suspected sphincter of oddi dysfunction were excluded. Therapy included single or multiple biliary stents with or without sphincterotomy. The incidence of RBD, the number of ERCP corrective sessions, and the type of endoscopic interventions were recorded. Successful response to endoscopic therapy was defined as resolution of RBD with normalization of associated cholestasis. Laboratory data and pertinent radiographic imaging noted included the pre-ERCP period and a follow up period of 6-12 mo after the last ERCP intervention.
RESULTS: One thousand two hundred and eighty-two patient records who received OLT from 1992 through 2011 were reviewed. Two hundred and twenty-four patients underwent ERCP for suspected BTC. RBD was reported in each of the initial cholangiograms. Twenty-one out of 1282 (1.6%) were identified as having RBD. There were 12 men and 9 women, average age of 59.6 years. Primary indication for ERCP was cholestatic pattern of liver associated biomarkers. Nineteen out of 21 patients underwent endoscopic therapy and 2/21 required immediate surgical intervention. In the endoscopically managed group: 65 ERCP procedures were performed with an average of 3.4 per patient and 1.1 stent per session. Fifteen out of 19 (78.9%) patients were successfully managed with biliary stenting. All stents were plastic. Selection of stent size and length were based upon endoscopist preference. Stent size ranged from 7 to 11.5 Fr (average stent size 10 Fr); Stent length ranged from 6 to 15 cm (average length 9 cm). Concurrent biliary sphincterotomy was performed in 10/19 patients. Single ERCP session was sufficient in 6/15 (40.0%) patients, whereas 4/15 (26.7%) patients needed two ERCP sessions and 5/15 (33.3%) patients required more than two (average of 5.4 ERCP procedures). Single biliary stent was sufficient in 5 patients; the remaining patients required an average of 4.9 stents. Four out of 19 (21.1%) patients failed endotherapy (lack of resolution of RBD and recurrent cholestasis in the absence of biliary stent) and required either choledocojejunostomy (2/4) or percutaneous biliary drainage (2/4). Endoscopic complications included: 2/65 (3%) post-ERCP pancreatitis and 2/10 (20%) non-complicated post-sphincterotomy bleeding. No endoscopic related mortality was found. The medical records of the 15 successful endoscopically managed patients were reviewed for a period of one year after removal of all biliary stents. Eleven patients had continued resolution of cholestatic biomarkers (73%). One patient had recurrent hepatitis C, 2 patients suffered septic shock which was not associated with ERCP and 1 patient was transferred care to an outside provider and records were not available for our review.
CONCLUSION: Although surgical biliary reconstruction techniques have improved, RBD represents a post-OLT complication. This entity is rare however, endoscopic management of RBD represents a reasonable initial approach.
Redundant bile duct; Orthotopic liver transplantation; Biliary complications; Biliary stent; Endoscopic retrograde cholangiopancreatography
Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Pancreatic duct stent insertion after ERCP has been widely accepted as the standard of care for the prevention of this complication in high-risk patients. Unfortunately, the placement of pancreatic stents requires higher level of endoscopic expertise and is not always feasible due to anatomic considerations. Therefore, effective non-invasive pharmacologic prophylaxis remains appealing, particularly if it is inexpensive, easily administered, has a low risk side effect profile and is widely available. There have been multiple studies evaluating potential pharmacologic candidates for post-ERCP pancreatitis (PEP) prophylaxis, most of them yielding disappointing results. A recently published large, multi-center, randomized controlled trial reported that in high risk patients a single dose of rectal indomethacin administered immediately after the ERCP significantly decreased the incidence of PEP compare to placebo.
Non-steroidal anti-inflammatory drugs; Indomethacin; Post-endoscopic retrograde cholangiopancreatography pancreatitis; Acute pancreatitis
AIM: To assess the efficacy of intramuscular diclofenac and fluid replacement for prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis.
METHODS: A prospective, placebo-controlled study was conducted in 80 patients who underwent ERCP. Patients were randomized to receive parenteral diclofenac at a loading dose of 75 mg followed by the infusion of 5-10 mL/kg per hour isotonic saline over 4 h after the procedure, or the infusion of 500 mL isotonic saline as placebo. Patients were evaluated clinically, and serum amylase levels were measured 4, 8 and 24 h after the procedure.
RESULTS: The two groups were matched for age, sex, underlying disease, ERCP findings, and type of treatment. The overall incidence of pancreatitis was 7.5% in the diclofenac group and 17.5% in the placebo group (12.5% in total). There were no significant differences in the incidence of pancreatitis and other variables between the two groups. In the subgroup analysis, the frequency of pancreatitis in the patients without sphincter of Oddi dysfunction (SOD) was significantly lower in the diclofenac group than in the control group (P = 0.047).
CONCLUSION: Intramuscular diclofenac and fluid replacement lowered the rate of pancreatitis in patients without SOD.
Endoscopic retrograde cholangiopancrea-tography; Pancreatitis; Diclofenac; Nonsteroidal anti-inflammatory drugs; Fluid replacement
Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In spite of continuing research, no pharmacologic agent capable of effectively reducing the incidence of ERCP-induced pancreatitis has found its way into clinical practise. A number of experimental studies suggest that intrapancreatic calcium concentrations play an important role in the initiation of intracellular protease activation, an initiating step in the course of acute pancreatitis. Magnesium can act as a calcium-antagonist and counteracts effects in calcium signalling. It can thereby attenuate the intracellular activation of proteolytic digestive enzymes in the pancreas and reduces the severity of experimental pancreatitis when administered either intravenously or as a food supplement.
We designed a randomized, double-blind, placebo-controlled phase III study to test whether the administration of intravenous magnesium sulphate before and after ERCP reduces the incidence and the severity of post-ERCP pancreatitis. A total of 502 adult patients with a medical indication for ERCP are to be randomized to receive either 4930 mg magnesium sulphate (= 20 mmol magnesium) or placebo 60 min before and 6 hours after ERCP. The incidence of clinical post-ERCP pancreatitis, hyperlipasemia, pain levels, use of analgetics and length of hospital stay will be evaluated.
If magnesium sulphate is found to be effective in preventing post-ERCP pancreatitis, this inexpensive agent with limited adverse effects could be used as a routine pharmacological prophylaxis.
Current Controlled Trials
Animal studies have demonstrated a role for substance P binding to neurokinin-1 receptor in the pathogenesis of acute pancreatitis. Our aim was to assess the efficacy of a neurokinin-1 receptor antagonist (aprepitant) at preventing post-ERCP pancreatitis in high risk patients.
Randomized, double-blind, placebo controlled trial at a single academic medical center. Patients at high risk for post-ERCP pancreatitis received either placebo or oral aprepitant administered 4 hours prior to ERCP, 80 mg 24 hours after the first dose, and then 80 mg 24 hours after the second dose. Fisher's exact test was used to compare incidence of post-ERCP pancreatitis in the two groups.
34 patients received aprepitant and 39 patients received placebo. Baseline characteristics were similar between the two groups. Incidence of acute pancreatitis was 7 in the aprepitant group and 7 in the placebo group. Hospitalization within 7 days post-procedure for abdominal pain that did not meet criteria for acute pancreatitis occurred in 6 and 9 patients in the aprepitant and placebo groups respectively (p=0.77).
Aprepitant did not lower incidence of post-ERCP pancreatitis in this preliminary human study. Larger studies potentially using the recently available intravenous formulation are necessary to conclusively clarify the efficacy of aprepitant in this setting.
Background. Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP) procedure and there are some reports showing cytokine changes in ERCP-induced pancreatits. Goals. To investigate the association between early changes (within 24 hours) in the serum interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)α, and IL-6 levels and the development of post-ERCP pancreatitis. Study. Forty five consecutive patients who underwent therapeutic ERCP and 10 patients with acute pancreatitis without ERCP were enrolled to the study. Serum concentrations of IL-2, IL-4, TNFα, and IL-6 were determined immediately before, 12 hours and 24 hours after ERCP. Results. Seven of the 45 patients (15.5%) developed post-ERCP pancreatitis. The levels of IL-4 at 24 hours after ERCP were significantly lower in the patients with post-ERCP pancreatitis than in those without pancreatitis, while TNFα levels at 12 hours after ERCP were higher in the complicated group than those of the uncomplicated group. The ratios of TNFα/IL-4 at 12 and 24 hours after ERCP were found significantly higher in the patients with post-ERCP pancreatitis than in those without pancreatitis. IL-6 in the complicated patients was found significantly increased at 24 hours after ERCP. Conclusions. The enhancement of serum TNFα and IL-6 levels in the patients with ERCP-induced pancreatitis reflects the inflammatory activity. Additionally, these cytokines together with IL-4 can be used in clinical laboratory monitoring of ERCP.
AIM: To investigate the effect of nonsteroidal anti-inﬂammatory drugs (NSAIDs) on the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).
METHODS: Two independent reviewers searched PubMed (1966 to October 2013), Embase (1984 to October 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 4, 2013) for relevant randomized controlled trials (RCTs) studying the effectiveness of prophylactic NSAID administration in the prevention of PEP. Using the Cochrane Collaboration Handbook, meta-analyses were conducted to evaluate the overall effect of NSAIDs in preventing the incidences of PEP and moderate to severe pancreatitis.
RESULTS: Eight RCTs were identified from the literature search and included 1883 patients that underwent ERCP, with 971 patients in the NSAID group and 912 patients in the placebo group. Sixty-nine out of 971 (7.11%) patients developed PEP in the NSAID group in comparison to 143 out of 912 (15.68%) patients in the placebo group. The pooled RR of PEP incidence with prophylactic NSAID administration was 0.43 (95%CI: 0.33-0.56), which demonstrates that NSAID administration after ERCP significantly reduced the incidence of PEP when compared to the placebo group (P < 0.0001). Subgroup analysis was performed and revealed that the presence (NSAID group) or absence (placebo group) of NSAIDs had no significant effect on the development of moderate to severe pancreatitis (RR = 0.79, 95%CI: 0.52-1.18). Moreover, the administration of NSAIDs as a rectal suppository (RR = 0.35, 95%CI: 0.26-0.48; P < 0.0001) was more effective than oral administration (RR = 0.97, 95%CI: 0.53-1.80) or through infusion (RR = 0.43, 95%CI: 0.12-1.54).
CONCLUSION: NSAIDs effectively reduce the incidence of PEP but not of moderate to severe pancreatitis.
Nonsteroidal anti-inﬂammatory drugs; Post-endoscopic retrograde cholangiopancreatography pancreatitis; Randomized controlled trial; Meta-analysis
AIM: To study if the angiotensin II receptor blockers (ARB) losartan counteracts pancreatic hyperenzymemia as measured 24 h after endoscopic retrograde cholangiopancreatography (ERCP).
METHODS: A triple-blind and placebo-controlled randomized clinical trial was performed at two Swedish hospitals in 2006-2008. Patients over 18 years of age undergoing ERCP, excluding those with current pancreatitis, current use of ARB, and severe disease, such as sepsis, liver and renal failure. One oral dose of 50 mg losartan or placebo was given one hour before ERCP. The relative risk of hyperenzymemia 24 h after ERCP was estimated using multivariable logistic regression, and expressed as odds ratio with 95% confidence intervals (CIs), including adjustment for potential remaining confounding.
RESULTS: Among 76 participating patients, 38 were randomized to the losartan and the placebo group, respectively. The incidence rates of hyperenzymemia and acute pancreatitis among all 76 participating patients were 21% and 12%, respectively. Hyperenzymemia was detected in 9 and 7 patients in the losartan and placebo group, respectively. There were no major differences between the comparison groups regarding cannulation difficulty, findings, or proportion of patients requiring drainage of the bile ducts. There were, however, more pancreatic duct injections, a greater extent of pancreatography, and more biliary sphincterotomies in the losartan group than in the placebo group. Losartan was not associated with risk of hyperenzymemia compared to the placebo group after multi-varible logistic regression analysis (odds ratio 1.6, 95%CI 0.3-7.8).
CONCLUSION: In this randomized trial 50 mg losartan given orally had no prophylactic effect on development of hyperenzymemia after ERCP.
Renin-angiotensin system; Pancreatitis; Prophylaxis; Placebo-controlled trial
Several studies have evaluated predictors for complications of endoscopic retrograde cholangiopancreatography (ERCP), but their relative importance is unknown. In addition, currently used blood tests to detect post-ERCP pancreatitis are inconsistent. The aim of this study was to determine predictors of post-ERCP complications that could discriminate between patients at highest and lowest risk of post-ERCP complications and to develop a model that is able to identify patients that can safely be discharged shortly after ERCP.
In a single-center, retrospective analysis over the period 2002–2007, predictors of post-ERCP complications were evaluated in a multivariable analysis and compared with those identified from a literature review. A prognostic model was developed based on these risk factors, which was further evaluated in a prospective patient population.
From our retrospective analysis and literature review, we selected the eight most important risk factors for post-ERCP pancreatitis and cholangitis. In the prognostic model, the risk factors (precut) sphincterotomy, sphincter of Oddi dysfunction, younger age, female gender, history of pancreatitis, pancreas divisum, and difficult cannulation accounted for a score of 1 each, whereas primary sclerosing cholangitis (PSC) accounted for a score of 2. A sum score of 4 or more in the prognostic model was associated with a high risk of developing pancreatitis and cholangitis (27%; 6/22) in the prospective patient population, whereas a sum score of 3 or less was associated with a low to intermediate risk (8%; 20/252).
We identified specific patient- and procedure-related factors that are associated with post-ERCP complications. The prognostic model based on these factors is able to identify patients who can be safely discharged the same day after ERCP.
ERCP; Complications; Risk factors; Early discharge
Background: Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). The beneficial effects of pharmaco-logic treatment of acute pancreatitis are unclear. Although the prophylactic use of NSAIDs for the reduction of the risk for pancreatic injury after ERCP has been assessed, the beneficial effects of NSAIDs on pancreatic injury are still being debated.
Objective: The aim of this study was to determine the effectiveness and tolerability of NSAIDs in the prophylaxis of post-ERCP pancreatitis (PEP).
Methods: MEDLINE (January 1966–January 2009), EMBASE (January 1966–January 2009), and the Cochrane Central Register of Controlled Trials (Issue 1, 2009) were searched using the key terms: pancreatitis, post-ERCP pancreatitis, nonsteroidal anti-inflammatory drugs, indomethacin, and diclofenac. The methods recommended by the Cochrane Collaboration and the Quality of Reporting Meta-Analyses guideline were used to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) of NSAIDs in the prevention of PEP.
Results: Four multinational RCTs were included in the meta-analysis (969 patients). The pooled odds ratio for NSAIDs for mild PEP was 0.69 (95% CI, 0.40–1.17; P = NS); moderate to severe PEP, 0.22 (95% CI, 0.05–1.01; P = 0.05); PEP (pooled), 0.44 (95% CI, 0.21–0.93; P = 0.03); in high-risk patients, 0.49 (95% CI, 0.17–1.39; P = NS); and in low-risk patients, 0.29 (95% CI, 0.12–0.71; P = 0.006). No evidence of publication bias was found.
Conclusion: Based on the findings from the present systematic review of 4 RCTs, NSAIDs were effective and well tolerated in the prevention of PEP, especially in low-risk patients.
NSAIDs; post-endoscopic retrograde cholangiopancreatography pancreatitis; prevention; randomized controlled trial; meta-analysis
Endoscopic retrograde cholangiopancreatography (ERCP) is now the exclusive endoscopic therapeutic modality for biliary as well as pancreatic diseases. The aim of the present study was to investigate patient- and procedure-related risk factors for post-ERCP complications in a large-scale study of procedures performed by a single experienced endoscopist.
This is a retrospective cohort study which included a total of 2,715 therapeutic ERCPs enrolled in the final analysis. Potential important patient- and procedure-related risk factors for overall post-ERCP complications, pancreatitis and post-endoscopic sphincterotomy (ES) bleeding were investigated by univariate and multivariate analyses.
Following the first therapeutic ERCP, 327 patients suffered complications; pancreatitis was observed in 132 (4.9%) patients, hemorrhage in 122 (4.5%) patients, cholangitis in 63 (2.3%) patients, perforation in 3 (0.11%) patients, and basket impaction in 7 (0.26%) patients. History of acute pancreatitis was more common in patients with post-ERCP complications (P<0.001). Female gender, young age (<40 years), periampullary diverticulum, suspected sphincter of Oddi dysfunction, metal stent placement, opacification of main pancreatic duct and suprapapillary fistulotomy were not found to be risk factors for overall post-ERCP complications and post-ERCP pancreatitis (PEP). Multivariate analysis showed a history of acute pancreatitis, difficult cannulation, needle-knife papillotomy, transpancreatic sphincterotomy, opacification of first and second class pancreatic ductules and acinarization as independent risk factors for overall complications and PEP, whereas antiplatelet and anticoagulation drug use were not found to be independent risk factors for post-ES bleeding.
The results of this study demonstrate that the endoscopist’s experience reduces patient- and procedure-related risk factors for post-ERCP complications.
Post-ERCP complications; risk factors; post-ERCP pancreatitis; post-endoscopic sphincterotomy bleeding
A preliminary study has shown increased pancreatic fat in patients with idiopathic pancreatitis and sphincter of Oddi dysfunction. In this study, we aimed to determine if an increased quantity of pancreatic fat is an independent risk factor for pancreatitis post-endoscopic retrograde cholangiopancreatography (ERCP).
In this case control study, we retrospectively reviewed a local radiological and ERCP database to identify patients who had had abdominal magnetic resonance imaging (MRI) followed by ERCP no more than 60 days later between September 2003 and January 2011. Percentage of fat was determined by recording signal intensity in the in-phase (Sin) and out-of-phase (Sout) T1-weighted gradient sequences, and calculation of the fat fraction as (Sin − Sout)/(Sin) × 2 by an abdominal radiologist blinded to clinical history. Controls matched for age, gender, and other pancreatobiliary disease were selected from a group with no post-ERCP pancreatitis (before fat content of the pancreas was analyzed).
Forty-seven patients were enrolled. Compared with controls, subjects with post-ERCP pancreatitis were similar in terms of age (41.4 years versus 41.1 years), gender (21.2% versus 20.2% males), pancreatobiliary disease characteristics, and most ERCP techniques. Measurements of pancreatic head, body, and tail fat and body mass index were similar in patients and controls.
Increased pancreatic fat on MRI criteria is not an independent predictor of post-ERCP pancreatitis.
magnetic resonance imaging; obesity; pancreatic fat; post-ERCP pancreatitis; sphincter of Oddi dysfunction
The paucity of controlled data for the treatment of most biliary sphincter of Oddi disorder (SOD) types and the incomplete response to therapy seen in clinical practice and several trials has generated controversy as to the best course of management of these patients. In this observational study we aimed to assess the outcome of patients with biliary SOD managed without sphincter of Oddi manometry.
Fifty-nine patients with biliary SOD (14% type I, 51% type II, 35% type III) were prospectively enrolled. All patients with a dilated common bile duct were offered endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy whereas all others were offered medical treatment alone. Patients were followed up for a median of 15 months and were assessed clinically for response to treatment.
At follow-up 15.3% of patients reported complete symptom resolution, 59.3% improvement, 22% unchanged symptoms, and 3.4% deterioration. Fifty-one percent experienced symptom resolution/improvement on medical treatment only, 12% after sphincterotomy, and 10% after both medical treatment/sphincterotomy. Twenty percent experienced at least one recurrence of symptoms after initial response to medical and/or endoscopic treatment. Fifty ERCP procedures were performed in 24 patients with an 18% complication rate (16% post-ERCP pancreatitis). The majority of complications occurred in the first ERCP these patients had. Most complications were mild and treated conservatively. Age, gender, comorbidity, SOD type, dilated common bile duct, presence of intact gallbladder, or opiate use were not related to the effect of treatment at the end of follow-up (p > 0.05 for all).
Patients with biliary SOD may be managed with a combination of endoscopic sphincterotomy (performed in those with dilated common bile duct) and medical therapy without manometry. The results of this approach with regards to symptomatic relief and ERCP complication rate are comparable to those previously published in the literature in cohorts of patients assessed by manometry.
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. Inclusion 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 post-ERCP 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.
Pancreatic stent; Endoscopic retrograde cholangiopancreatography; Pancreatitis; Hyperamylasemia; Meta-analysis
Acute pancreatitis remains the most common major complication of endoscopic retrograde cholangiopancreatography (ERCP). The pathogenesis of post-ERCP acute pancreatitis may be mediated by oxygen-derived free radicals, which could be ameliorated by antioxidants. Antioxidant supplementation may potentially prevent post-ERCP pancreatitis. We performed a meta-analysis of randomized controlled trials to evaluate the effect of prophylactic antioxidant supplementation compared with control on the prevention of post-ERCP pancreatitis.
PubMed and Embase databases were searched to identify relevant trials. A standardized Excel file was used to extract data by two independent authors. Results were expressed as risk ratio (RR) with accompanying 95% confidence interval (CI). The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity.
Eleven studies involving 3,010 patients met our inclusion criteria. Antioxidant supplementation did not significantly decrease the incidence of post-ERCP pancreatitis (RR, 0.92; 95% CI, 0.65-1.32; P = 0.665). There was also no statistical difference in the severity grades between the antioxidant group and control group.
Based on current evidence, antioxidant supplementation shows no beneficial effect on the incidence and the severity of post-ERCP pancreatitis; thus, there is currently a lack of evidence to support using antioxidants for the prevention of post-ERCP pancreatitis.
Antioxidant; Endoscopic retrograde cholangiopancreatography; Pancreatitis