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Pancreatic stent placement remains a cornerstone of prevention of post-ERCP pancreatitis, but it requires specialized techniques
EDITORIAL
Pancreatic stent placement remains a cornerstone of prevention of post-ERCP pancreatitis, but it requires specialized techniques Major progress has been made toward understanding and preventing post-ERCP pancreatitis (PEP), an adverse event that was previously viewed as mostly unpredictable and unpreventable. Approaches toward the prevention of PEP can easily be oversimplified and have gone through an evolution of trends. Attention has been focused on patient selection (avoiding sphincter of Oddi [SOD] dysfunction will prevent the problem), then technique (wire cannulation will prevent all evil), then pancreatic stents (universal solution), and most recently rectal nonsteroidal anti-inflammatory drugs (NSAIDs) (the new panacea, which will obviate any technical aspects). Risk factors and preventive strategies regarding PEP can be categorized into the 4 “Ps”: patient-related factors, procedural technique, pancreatic stents, and pharmacologic prophylaxis.1 As usual, the truth is in the middle somewhere. Patient-related factors have emerged as strong influences on the potential for PEP in multiple prospective studies. Independent risk factors include suspected SOD dysfunction, young age, and a history of PEP. In such high-risk patients, especially those with combinations of risk factors, the risk of PEP was as high as 20% in the era preceding the widespread use of prophylactic pancreatic stents. By contrast, in mixed-risk patients, the reported rates of PEP have been typically about 5%. This observation leads to an obvious conclusion: Do not perform ERCP in patients with marginal indication or benefit, especially in a setting with marginal expertise! Procedural factors include any pancreatic manipulation, intentional or inadvertent. Pancreatic duct (PD) instrumentation, PD injection, PD sphincterotomy, and difficult biliary cannulation, precut sphincterotomy, balloon dilation of the intact sphincter, and recently placement of metal biliary stents2 have all been shown to increase the risk of PEP. Several studies have recently shown that deep pancreatic guidewire passage alone (independent of contrast medium injection) is in fact a major risk unless it is followed by a pancreatic stent.2-5 Although the mere avoidance of PD manipulation or injection might seem appealing, it is often not possible and, even if possible, is not sufficient in high-risk patients. So,
slick technique in biliary cannulation alone is not the answer. Pancreatic stent placement (PSP) is the most rigorously studied prophylactic measure for the prevention of PEP and, we believe, is the most consistently demonstrated and effective way of reducing the risk of PEP. It has been shown to decrease the risk of PEP by 60% to 80% in patients both at high risk (12 studies) and on those at low to mixed risk (2 studies). In the latest meta-analysis, which was the first to include studies of lower-risk patients, PD stent placement was shown to reduce the risk of mild
Does the study by Choksi and colleagues suggest that use of indomethacin obviates the need for pancreatic stent placement? We think not.
Copyright ª 2015 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2014.09.020
and moderate as well as severe PEP.6 PD stent placement is currently considered the standard of care in high-risk circumstances and is also being increasingly performed even in “routine” low-risk to medium-risk ERCP.7 The limitations of PD stent placement include unsuccessful stent placement (eg, inability to advance a wire into PD, or inability to place a stent after wire placement, resulting in an increased risk of PEP), inadvertent duct injury during stent placement, long-term stent-related duct injury, and need for follow-up after stent placement. A major problem with pancreatic stents is variable expertise and familiarity with their placement. So, PD stent placement alone may not be the whole answer, especially in less-specialized hands. Pharmacologic prophylaxis has the benefit of being noninvasive and offers a potentially inexpensive and nontoxic approach to prevent PEPda long-sought-after goal that is nearing realization. Rectal nonsteroidal antiinflammatory drugs (NSAIDs) have now been shown to reduce the risk of PEP by about 50% to 60%, with at least 6 positive randomized controlled trials (RCTs), and its efficacy has been confirmed by numerous meta-analyses.1 Multiple other pharmacologic agents have been studied, though not as rigorously, and some such as nitroglycerin derivatives have also shown promise, though mainly in
156 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 1 : 2015
www.giejournal.org
Arain and Freeman
Editorial
the setting of low-risk to mixed-risk patients. At present, the only agents that have clearly been shown to decrease the risk of PEP are rectal NSAIDs. The pivotal study of pharmacologic prophylaxis, which has had a significant impact on clinical practice since it was first published, is an RCT by Elmunzer and colleagues8 in which they studied the role of rectal indomethacin in high-risk patients, mostly with SOD dysfunction (82%), in multiple tertiary referral academic centers. The authors reported on 602 patients randomized to receive rectal indomethacin or placebo, with overall PEP rates of 9.2% (27/295) and 16.9% (52/307) with and without indomethacin. The benefit from indomethacin was significant despite relatively high rates of PD stent placement (O80%) in both groups. Some observations to keep in mind about this study: 95% of patients were randomized at 2 centers, and the benefit of rectal NSAIDs was nonsignificant at the largest single contributing center, which was also the center with the highest success at placement of PD stents; and even with an NSAID rate of PEP was relatively high at 9.2%. Thus, it is hard to be convinced that rectal NSAIDs represent the universal panacea for PEP. In this context, in the current issue of Gastrointestinal Endoscopy, using data from the RCT, the same investigators present a study on the role of indomethacin for PEP prophylaxis in patients in whom PSP was not successful. The study by Choksi and colleagues9 is a post-hoc analysis of data collected from 2 of the 4 centers: Indiana University (IU) and University of Michigan (UM). The authors identified all patients who did not have a pancreatic stent placed, and they used 5 criteria to create a post-hoc definition of pancreatic stent failure. Patients without a stent and not meeting the criteria were defined as having had no attempt at PSP). The rate of pancreatic stent failure was 2.4% at IU (10/403 patients) and 19.5% at UM (32/164 patients), with a relative risk odds ratio 6.87 (95% confidence interval, 3.0315.59). Other factors associated with pancreatic stent failure were older age and difficult cannulation. The PEP rates in patients with pancreatic stent failure, PSP, and no PSP in the placebo group were 34%, 16%, and 12%, respectively. The difference between the failed PD stent group and PSP and no PSP groups reached statistical significance (0.04 and 0.02). The PEP rates for the 3 groups in the indomethacin group were as follows: pancreatic stent failure 5.3%, PSP 10.3%m and no PSP 9.6%. There was no statistical difference between the failed PD stent group and the other 2 groups. On multivariate analysis of the entire cohort, pancreatic stent failure was associated with an increased risk of pancreatitis only when it occurred in the absence of rectal indomethacin (34% vs 5.3%, P Z .027). On the basis of these results, the authors concluded that (1) the increased risk associated with failed PSP can be decreased by administration of rectal indomethacin, (2) rectal indomethacin should be given to all high risk patients and (3) development of proficiency and expertise in PSP should be sought before PSP is attempted.
The study by Choksi et al9 has to be interpreted in the context of limitations associated with post-hoc analyses. The primary goal of the data collection in the original RCT was different (to determine the role of indomethacin vs placebo for PEP prophylaxis) from that in the current study, and the definition of the failed PSP was based on criteria determined after the original data collection. The primary outcome of interest, failed PD stent placement, is not a categorical variable, which can be easily identified, but was rather inferred on the basis of criteria devised for the study. Patients without a stent who did not meet the criteria for pancreatic stent failure were assumed to have undergone no attempt at PD stent placement. Given the relatively small numbers in these groups (considering that O80% of patients of patients had stents placed), incorrect placement in just a few patients may result in differences that reach significance. By extension, the difference in PEP rate in pancreatic stent failure (34%) versus PSP (16%) in the placebo group would become statistically insignificant by the addition of just 1 more patient to the PSP group. Assuming that the reported data accurately identify patients with failed PSP, in the entire cohort, for patients with pancreatic stent failure, the rate of pancreatitis was significantly lower in patients who received indomethacin compared with the placebo group, which is suggestive of a protective effect of indomethacin. The same investigators are in the process of initiating an RCT comparing the role of rectal indomethacin with pancreatic stents, which is likely to shed light on the relative roles of both modalities for PEP prophylaxis. Perhaps the most interesting finding in the study by Choksi and colleagues9 is the significantly higher risk of failed PSP based on study site: UM 19.5% versus IU 2.4%, relative risk 6.87. The authors are to be congratulated for openly revealing these data. Interestingly, in the original RCT, the pancreatitis rates in both the placebo and the indomethacin groups also differed considerably by institution: UM placebo 28.7% versus indomethacin 14.3%; IU placebo 12.7 versus indomethacin 7.3; the latter difference was not statistically significant despite randomization of 413 patients. Although it is not possible to make a direct link between failed PSP and overall risk of pancreatitis, and definitions of PEP depend heavily on policy with respect to overnight observation and especially keeping patients in the hospital a second night, this does raise the possibility of differences in pancreatitis rates potentially being associated with procedural technique, including PSP. The authors acknowledge that such differences exist and warrant further study. The study by Choksi and colleagues9 leads to several conclusions and raises several questions. First, it does confirm that attempting to place a pancreatic stent with guidewire manipulation but failing to deliver the stent infers substantial risk of PEP. This observation confirms a report from 10 years ago in which attempted PSP was
www.giejournal.org
Volume 81, No. 1 : 2015 GASTROINTESTINAL ENDOSCOPY 157
Editorial
defined prospectively.10 In that study, it was shown that use of a small-caliber 0.01800 wire with knuckling of the tip a short distance inside the duct allowed universal success at PD stent placement, even in patients with difficult, small, or tortuous PDs in whom the wire could not be passed more deeply. The best guidewire and technique for placement of pancreatic stents is a matter of contention among experts. It is our opinion that smaller wires and physician-controlled wires are key, but there are many factors involved with technical success and many ways to achieve that end. Whatever the best technique, specific training in pancreatic therapeutic techniques to place protective stents, if not to perform pancreatic endotherapy, is essential for every endoscopist performing ERCP. A wide variety of audiovisual educational resources to improve PD access and stenting is available from the American Society for Gastrointestinal Endoscopy (www.asge.org), including 2 by the current authors (DV #035 and #043). Does the study by Choksi and colleagues9 suggest that the use of indomethacin obviates the need for PSP? We think not. This is a post-hoc analysis involving small numbers of patients with a post-hoc definition of failed PSP. It does open the way for a randomized trial of indomethacin alone versus indomethacin plus pancreatic stent to prevent PEP. In our experience, since we have adopted the nearly universal use of rectal indomethacin in high-risk ERCP, the only severe cases of PEP pancreatitis have occurred in high-risk patients who did in fact receive indomethacin but who had very unusual situations of either failed or not attempted PSP. We would thus caution readers from abandoning pancreatic stents just yet. Rather, endoscopists should focus on learning pancreas-specific techniques. All of the data discussed here point to the importance of attention to all 4 “Ps” of prevention of PEP.
Arain and Freeman
disclosed no financial relationships relevant to this publication. Mustafa A. Arain, MD Martin L. Freeman, MD Division of Gastroenterology, Hepatology, and Nutrition University of Minnesota Minneapolis, Minnesota, USA Abbreviations: PEP, post-ERCP pancreatitis; PSP, pancreatic stent placement; RCT, randomized controlled trial; SOD, sphincter of Oddi.
REFERENCES
The following author disclosed financial relationships relevant to this publication. M. L. Freeman is a consultant with Boston Scientific and has received speaking honoraria from Cook Endoscopy. All other authors
1. Arain MA, Freeman ML. Pharmacologic prophylaxis alone is not adequate to prevent post-ERCP pancreatitis. Am J Gastroenterol 2014;109:910-24. 2. Coté GA, Kumar N, Ansstas M, et al. Risk of post-ERCP pancreatitis with placement of self-expandable metallic stents. Gastrointest Endosc 2010;72:748-54. 3. Wang P, Li ZS, Liu F, et al. Risk factors for ERCP-related complications: a prospective multicenter study. Am J Gastroenterol 2009;104:31-40. 4. Ito K, Fujita N, Noda Y, et al. Can pancreatic duct stenting prevent postERCP pancreatitis in patients who undergo pancreatic duct guidewire placement for achieving selective biliary cannulation? A prospective randomized controlled trial. J Gastroenterol 2010;45:1183-91. 5. Halttunen J, Meisner S, Aabakken L, et al. Difficult cannulation as defined by a prospective study of the Scandinavian Association for Digestive Endoscopy (SADE) in 907 ERCPs. Scand J Gastroenterol 2014;49:752-8. 6. Mazaki T, Mado K, Masuda H, et al. Prophylactic pancreatic stent placement and post-ERCP pancreatitis: an updated meta-analysis. J Gastroenterol 2014;49:343-55. 7. Freeman ML. Pancreatic stents for prevention of post-ERCP pancreatitis: for everyday practice or for experts only? Gastrointest Endosc 2010;71:940-4. 8. Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012;366:1414-22. 9. Choksi NS, Fogel EL, Cote GA, et al. The risk of post-ERCP pancreatitis and the protective effect of rectal indomethacin in cases of attempted but unsuccessful prophylactic pancreatic stent placement. Gastrointest Endosc 2014;81:150-5. 10. Freeman ML, Overby CS, Qi DF. Pancreatic stent insertion: consequences of failure, and results of a modified technique to maximize success. Gastrointest Endosc 2004;59:8-14.
158 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 1 : 2015
www.giejournal.org
DISCLOSURE
Pancreatic stent placement remains a cornerstone of prevention of post-ERCP pancreatitis, but it requires specialized techniques Major progress has been made toward understanding and preventing post-ERCP pancreatitis (PEP), an adverse event that was previously viewed as mostly unpredictable and unpreventable. Approaches toward the prevention of PEP can easily be oversimplified and have gone through an evolution of trends. Attention has been focused on patient selection (avoiding sphincter of Oddi [SOD] dysfunction will prevent the problem), then technique (wire cannulation will prevent all evil), then pancreatic stents (universal solution), and most recently rectal nonsteroidal anti-inflammatory drugs (NSAIDs) (the new panacea, which will obviate any technical aspects). Risk factors and preventive strategies regarding PEP can be categorized into the 4 “Ps”: patient-related factors, procedural technique, pancreatic stents, and pharmacologic prophylaxis.1 As usual, the truth is in the middle somewhere. Patient-related factors have emerged as strong influences on the potential for PEP in multiple prospective studies. Independent risk factors include suspected SOD dysfunction, young age, and a history of PEP. In such high-risk patients, especially those with combinations of risk factors, the risk of PEP was as high as 20% in the era preceding the widespread use of prophylactic pancreatic stents. By contrast, in mixed-risk patients, the reported rates of PEP have been typically about 5%. This observation leads to an obvious conclusion: Do not perform ERCP in patients with marginal indication or benefit, especially in a setting with marginal expertise! Procedural factors include any pancreatic manipulation, intentional or inadvertent. Pancreatic duct (PD) instrumentation, PD injection, PD sphincterotomy, and difficult biliary cannulation, precut sphincterotomy, balloon dilation of the intact sphincter, and recently placement of metal biliary stents2 have all been shown to increase the risk of PEP. Several studies have recently shown that deep pancreatic guidewire passage alone (independent of contrast medium injection) is in fact a major risk unless it is followed by a pancreatic stent.2-5 Although the mere avoidance of PD manipulation or injection might seem appealing, it is often not possible and, even if possible, is not sufficient in high-risk patients. So,
slick technique in biliary cannulation alone is not the answer. Pancreatic stent placement (PSP) is the most rigorously studied prophylactic measure for the prevention of PEP and, we believe, is the most consistently demonstrated and effective way of reducing the risk of PEP. It has been shown to decrease the risk of PEP by 60% to 80% in patients both at high risk (12 studies) and on those at low to mixed risk (2 studies). In the latest meta-analysis, which was the first to include studies of lower-risk patients, PD stent placement was shown to reduce the risk of mild
Does the study by Choksi and colleagues suggest that use of indomethacin obviates the need for pancreatic stent placement? We think not.
Copyright ª 2015 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2014.09.020
and moderate as well as severe PEP.6 PD stent placement is currently considered the standard of care in high-risk circumstances and is also being increasingly performed even in “routine” low-risk to medium-risk ERCP.7 The limitations of PD stent placement include unsuccessful stent placement (eg, inability to advance a wire into PD, or inability to place a stent after wire placement, resulting in an increased risk of PEP), inadvertent duct injury during stent placement, long-term stent-related duct injury, and need for follow-up after stent placement. A major problem with pancreatic stents is variable expertise and familiarity with their placement. So, PD stent placement alone may not be the whole answer, especially in less-specialized hands. Pharmacologic prophylaxis has the benefit of being noninvasive and offers a potentially inexpensive and nontoxic approach to prevent PEPda long-sought-after goal that is nearing realization. Rectal nonsteroidal antiinflammatory drugs (NSAIDs) have now been shown to reduce the risk of PEP by about 50% to 60%, with at least 6 positive randomized controlled trials (RCTs), and its efficacy has been confirmed by numerous meta-analyses.1 Multiple other pharmacologic agents have been studied, though not as rigorously, and some such as nitroglycerin derivatives have also shown promise, though mainly in
156 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 1 : 2015
www.giejournal.org
Arain and Freeman
Editorial
the setting of low-risk to mixed-risk patients. At present, the only agents that have clearly been shown to decrease the risk of PEP are rectal NSAIDs. The pivotal study of pharmacologic prophylaxis, which has had a significant impact on clinical practice since it was first published, is an RCT by Elmunzer and colleagues8 in which they studied the role of rectal indomethacin in high-risk patients, mostly with SOD dysfunction (82%), in multiple tertiary referral academic centers. The authors reported on 602 patients randomized to receive rectal indomethacin or placebo, with overall PEP rates of 9.2% (27/295) and 16.9% (52/307) with and without indomethacin. The benefit from indomethacin was significant despite relatively high rates of PD stent placement (O80%) in both groups. Some observations to keep in mind about this study: 95% of patients were randomized at 2 centers, and the benefit of rectal NSAIDs was nonsignificant at the largest single contributing center, which was also the center with the highest success at placement of PD stents; and even with an NSAID rate of PEP was relatively high at 9.2%. Thus, it is hard to be convinced that rectal NSAIDs represent the universal panacea for PEP. In this context, in the current issue of Gastrointestinal Endoscopy, using data from the RCT, the same investigators present a study on the role of indomethacin for PEP prophylaxis in patients in whom PSP was not successful. The study by Choksi and colleagues9 is a post-hoc analysis of data collected from 2 of the 4 centers: Indiana University (IU) and University of Michigan (UM). The authors identified all patients who did not have a pancreatic stent placed, and they used 5 criteria to create a post-hoc definition of pancreatic stent failure. Patients without a stent and not meeting the criteria were defined as having had no attempt at PSP). The rate of pancreatic stent failure was 2.4% at IU (10/403 patients) and 19.5% at UM (32/164 patients), with a relative risk odds ratio 6.87 (95% confidence interval, 3.0315.59). Other factors associated with pancreatic stent failure were older age and difficult cannulation. The PEP rates in patients with pancreatic stent failure, PSP, and no PSP in the placebo group were 34%, 16%, and 12%, respectively. The difference between the failed PD stent group and PSP and no PSP groups reached statistical significance (0.04 and 0.02). The PEP rates for the 3 groups in the indomethacin group were as follows: pancreatic stent failure 5.3%, PSP 10.3%m and no PSP 9.6%. There was no statistical difference between the failed PD stent group and the other 2 groups. On multivariate analysis of the entire cohort, pancreatic stent failure was associated with an increased risk of pancreatitis only when it occurred in the absence of rectal indomethacin (34% vs 5.3%, P Z .027). On the basis of these results, the authors concluded that (1) the increased risk associated with failed PSP can be decreased by administration of rectal indomethacin, (2) rectal indomethacin should be given to all high risk patients and (3) development of proficiency and expertise in PSP should be sought before PSP is attempted.
The study by Choksi et al9 has to be interpreted in the context of limitations associated with post-hoc analyses. The primary goal of the data collection in the original RCT was different (to determine the role of indomethacin vs placebo for PEP prophylaxis) from that in the current study, and the definition of the failed PSP was based on criteria determined after the original data collection. The primary outcome of interest, failed PD stent placement, is not a categorical variable, which can be easily identified, but was rather inferred on the basis of criteria devised for the study. Patients without a stent who did not meet the criteria for pancreatic stent failure were assumed to have undergone no attempt at PD stent placement. Given the relatively small numbers in these groups (considering that O80% of patients of patients had stents placed), incorrect placement in just a few patients may result in differences that reach significance. By extension, the difference in PEP rate in pancreatic stent failure (34%) versus PSP (16%) in the placebo group would become statistically insignificant by the addition of just 1 more patient to the PSP group. Assuming that the reported data accurately identify patients with failed PSP, in the entire cohort, for patients with pancreatic stent failure, the rate of pancreatitis was significantly lower in patients who received indomethacin compared with the placebo group, which is suggestive of a protective effect of indomethacin. The same investigators are in the process of initiating an RCT comparing the role of rectal indomethacin with pancreatic stents, which is likely to shed light on the relative roles of both modalities for PEP prophylaxis. Perhaps the most interesting finding in the study by Choksi and colleagues9 is the significantly higher risk of failed PSP based on study site: UM 19.5% versus IU 2.4%, relative risk 6.87. The authors are to be congratulated for openly revealing these data. Interestingly, in the original RCT, the pancreatitis rates in both the placebo and the indomethacin groups also differed considerably by institution: UM placebo 28.7% versus indomethacin 14.3%; IU placebo 12.7 versus indomethacin 7.3; the latter difference was not statistically significant despite randomization of 413 patients. Although it is not possible to make a direct link between failed PSP and overall risk of pancreatitis, and definitions of PEP depend heavily on policy with respect to overnight observation and especially keeping patients in the hospital a second night, this does raise the possibility of differences in pancreatitis rates potentially being associated with procedural technique, including PSP. The authors acknowledge that such differences exist and warrant further study. The study by Choksi and colleagues9 leads to several conclusions and raises several questions. First, it does confirm that attempting to place a pancreatic stent with guidewire manipulation but failing to deliver the stent infers substantial risk of PEP. This observation confirms a report from 10 years ago in which attempted PSP was
www.giejournal.org
Volume 81, No. 1 : 2015 GASTROINTESTINAL ENDOSCOPY 157
Editorial
defined prospectively.10 In that study, it was shown that use of a small-caliber 0.01800 wire with knuckling of the tip a short distance inside the duct allowed universal success at PD stent placement, even in patients with difficult, small, or tortuous PDs in whom the wire could not be passed more deeply. The best guidewire and technique for placement of pancreatic stents is a matter of contention among experts. It is our opinion that smaller wires and physician-controlled wires are key, but there are many factors involved with technical success and many ways to achieve that end. Whatever the best technique, specific training in pancreatic therapeutic techniques to place protective stents, if not to perform pancreatic endotherapy, is essential for every endoscopist performing ERCP. A wide variety of audiovisual educational resources to improve PD access and stenting is available from the American Society for Gastrointestinal Endoscopy (www.asge.org), including 2 by the current authors (DV #035 and #043). Does the study by Choksi and colleagues9 suggest that the use of indomethacin obviates the need for PSP? We think not. This is a post-hoc analysis involving small numbers of patients with a post-hoc definition of failed PSP. It does open the way for a randomized trial of indomethacin alone versus indomethacin plus pancreatic stent to prevent PEP. In our experience, since we have adopted the nearly universal use of rectal indomethacin in high-risk ERCP, the only severe cases of PEP pancreatitis have occurred in high-risk patients who did in fact receive indomethacin but who had very unusual situations of either failed or not attempted PSP. We would thus caution readers from abandoning pancreatic stents just yet. Rather, endoscopists should focus on learning pancreas-specific techniques. All of the data discussed here point to the importance of attention to all 4 “Ps” of prevention of PEP.
Arain and Freeman
disclosed no financial relationships relevant to this publication. Mustafa A. Arain, MD Martin L. Freeman, MD Division of Gastroenterology, Hepatology, and Nutrition University of Minnesota Minneapolis, Minnesota, USA Abbreviations: PEP, post-ERCP pancreatitis; PSP, pancreatic stent placement; RCT, randomized controlled trial; SOD, sphincter of Oddi.
REFERENCES
The following author disclosed financial relationships relevant to this publication. M. L. Freeman is a consultant with Boston Scientific and has received speaking honoraria from Cook Endoscopy. All other authors
1. Arain MA, Freeman ML. Pharmacologic prophylaxis alone is not adequate to prevent post-ERCP pancreatitis. Am J Gastroenterol 2014;109:910-24. 2. Coté GA, Kumar N, Ansstas M, et al. Risk of post-ERCP pancreatitis with placement of self-expandable metallic stents. Gastrointest Endosc 2010;72:748-54. 3. Wang P, Li ZS, Liu F, et al. Risk factors for ERCP-related complications: a prospective multicenter study. Am J Gastroenterol 2009;104:31-40. 4. Ito K, Fujita N, Noda Y, et al. Can pancreatic duct stenting prevent postERCP pancreatitis in patients who undergo pancreatic duct guidewire placement for achieving selective biliary cannulation? A prospective randomized controlled trial. J Gastroenterol 2010;45:1183-91. 5. Halttunen J, Meisner S, Aabakken L, et al. Difficult cannulation as defined by a prospective study of the Scandinavian Association for Digestive Endoscopy (SADE) in 907 ERCPs. Scand J Gastroenterol 2014;49:752-8. 6. Mazaki T, Mado K, Masuda H, et al. Prophylactic pancreatic stent placement and post-ERCP pancreatitis: an updated meta-analysis. J Gastroenterol 2014;49:343-55. 7. Freeman ML. Pancreatic stents for prevention of post-ERCP pancreatitis: for everyday practice or for experts only? Gastrointest Endosc 2010;71:940-4. 8. Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012;366:1414-22. 9. Choksi NS, Fogel EL, Cote GA, et al. The risk of post-ERCP pancreatitis and the protective effect of rectal indomethacin in cases of attempted but unsuccessful prophylactic pancreatic stent placement. Gastrointest Endosc 2014;81:150-5. 10. Freeman ML, Overby CS, Qi DF. Pancreatic stent insertion: consequences of failure, and results of a modified technique to maximize success. Gastrointest Endosc 2004;59:8-14.
158 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 1 : 2015
www.giejournal.org
DISCLOSURE