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EDITORIAL
Pancreatic stents for prevention of post-ERCP pancreatitis: for everyday practice or for experts only? Once thought to be unpredictable and inevitable, postERCP pancreatitis has benefitted from evolved understanding. Increasingly, combinations of patient-related and procedure-related risk factors allow reasonably accurate prediction of likelihood that an individual patient will develop this complication. Careful endoscopic technique and refinements such as wire-guided cannulation go only so far in avoiding pancreatitis and are not alone adequate to prevent this complication in high-risk patients. Pharmacologic prevention is mostly ineffective, impractical, or unavailable, and the ideal agent has not yet been found. There is now some hope that nonsteroidal antiinflammatory drugs might be the new “holy grail,” although it remains to be seen whether their efficacy will hold up in high-risk patients or in large-scale, multicenter trials. Placement of pancreatic stents is a relatively new and increasingly adopted approach to reducing the risk of post-ERCP pancreatitis.1 Originally introduced to treat pancreatic duct pathology such as strictures and duct leaks, pancreatic stents have long been suspected to reduce the risk of iatrogenic pancreatitis. The mechanism by which this might work is not clearly understood but probably involves preservation of pancreatic juice flow in the face of papillary and ductal trauma and perhaps removal of enzymatic “substrate” for the explosive cascade of events that can accompany the more severe forms of pancreatitis. Evidence for the efficacy of pancreatic stents in reducing post-ERCP pancreatitis continues to accumulate and is now fairly overwhelming. Efficacy has been provided by randomized, controlled trials of pancreatic stenting in various high-risk settings1 including manometrically documented sphincter of Oddi dysfunction (SOD), difficult cannulation, precut sphincterotomy, endoscopic ampullectomy, and, most recently, for pancreatic guidewire placement to assist biliary cannulation.2 One large trial even showed that pancreatic stent placement significantly reduced the risk in unselected ERCP (excluding pancreatic cancer, pancreas divisum, and intentional pancreatic drainage).3 The efficacy of pancreatic stents for risk reduction is also supported by retrospective, case-control stud-
Copyright © 2010 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 doi:10.1016/j.gie.2009.12.043
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ies in settings such as suspected SOD with normal manometry, biliary sphincter balloon dilation, pancreatic sphincterotomy for all indications, and pancreatic brush cytology.1 In summary, 16 of 17 studies of high-risk ERCP have shown either trends toward reduced rates or statistically significantly lower rates of post-ERCP pancreatitis in patients receiving pancreatic stents compared with those without pancreatic stents (Table 1). Statistical significance was reached in 6 of 8 randomized, controlled trials, and in all of those that were conducted since 1999. A metaanalysis of 5 studies suggested that in high-risk patients, placement of a pancreatic stent reduced the risk of pancreatitis by about two thirds and virtually eliminated the risk of severe post-ERCP pancreatitis, with number needed to treat (NNT) to prevent 1 episode of pancreatitis out of approximately 10.4 Although it is not necessary or practical to place a pancreatic stent in all ERCPs, one analysis suggested that cost-effectiveness would justify pancreatic stent placement in fully one half of all ERCPs, the proportion of all ERCPs that were estimated to be at high risk for the purposes of the model.5
Evidence for the efficacy of pancreatic stents in reducing post-ERCP pancreatitis continues to accumulate and is now fairly overwhelming.
Like any technique, though, there are downsides and controversies regarding pancreatic stent placement (Table 2). It can be difficult at times to decide whether an individual patient or case merits the added pancreatic instrumentation required for placement of a stent, and even experts may not agree.6 Once decided upon, placement of a pancreatic stent can be technically challenging, and occasionally impossible, even for the most experienced endoscopists. Techniques and equipment for accessing pancreatic ducts and deep placement of guidewires and stents in pancreatic ducts are quite different from those used for biliary access. The course of the duct being highly variable and frequently tortuous, combined with an often small caliber and the presence of multiple side branches, can lead to failed access, which may be worse than no attempt at all,7 or to guidewire perforation. Older published data report failure rates of pancreatic stent placewww.giejournal.org
Freeman
Editorial
TABLE 1. Studies of pancreatic stents for prevention of post-ERCP pancreatitis that included a control group without stent
First author, year
Design
Patients/procedures
No.
Pancreatitis % without and with pancreatic stent
P
Smithline 1993
RCT
Biliary ES for SOD, small ducts, or precut
93
18
14
.299
Sherman 1996 (abstract)
RCT
Precut biliary ES
93
21
2
.036
Tarnasky 1998
RCT
Biliary ES for SOD
80
26
7
0.03
Elton 1998
RCC
Pancreatic ES for all indications
194
12.5
0.7
⬍.003
Patel 1999 (abstract)
RCT
Pancreatic ES for SOD
36
33
11
⬎.05
Vandervoort 1999
PCC
Pancreatic brush cytology for suspected malignancy
42
28.1
0
.08
Aizawa 2001
RCC
Biliary balloon dilatation for stone
40
6
0
.11
Fogel 2002
RCC
Biliary ⫾ pancreatic ES for SOD
436
28.2
13.5
⬍.05
Norton 2002
RCC
Endoscopic ampullectomy
28
11.1
20
⬎.05
Fazel 2003
RCT
Difficult cannulation, biliary ES, SOD
76
28
5
⬍.05
Freeman 2004
PCC
Consecutive high-risk ERCP in which a major papilla PD stent was attempted
225
66.7
14.4
.06
Catalano 2004
RCC
Endoscopic ampullectomy
103
16.7
3.3
.10
Harewood 2005
RCT
Endoscopic ampullectomy
19
33.0
0
.02
Hookey 2006
RCC
Pancreatic ES (major and minor papilla) (majority with chronic pancreatitis)
572
19.3
8.8
.001
Sofuni 2007
RCT
All consecutive ERCP (excluding pancreatic cancer, PD drainage cases)
201
13.6
3.2
.02
Saad 2008
RCC
Suspected SOD with normal SO manometry
403
9.0
2.4
.006
Ito 2009 (abstract)
RCT
Pancreatic guidewire placement to assist selective biliary cannulation
69
23
2.9
.017
RCT, Randomized controlled trial; ES, endoscopic sphincterotomy; SOD, sphincter of Oddi dysfunction; RCC, retrospective case control; PCC, prospective case control; PD, pancreatic duct; SO, sphincter of Oddi.
ment as high as 5% or 10%, even for experts. Lower rates of failure are the rule now, but the data are difficult to interpret because many prospective studies require pancreatic duct access with at least contrast material and sometimes a guidewire before randomization takes place. Few are “intent to treat” studies that include patients considered for pancreatic stent prophylaxis before pancreatic duct anatomy is defined or access is obtained. The optimal choice of guidewires is debated at the highest levels, but, even at some advanced centers, endoscopists are not habituated to use of very small-caliber, 0.018-inch wires, which may be optimal for placing even a short stent in particularly challenging pancreatic ducts.7 Choice of pancreatic stents is also subject to disagreement among experts, mostly varying from 3F, generally at least 8 to 10 cm long without an inner flange, to 5F, typically only 2 or 3 cm in length.6 Recent data demonstrate that there is no particular advantage for long, 3F as opposed to short, 5F stent www.giejournal.org
placement, further implying that added manipulation and instrumentation required to pass a guidewire deep to the tail is probably not warranted just to place a stent.8 Then there is the increasing amount of literature on the risk of pancreatic duct damage because of pancreatic stents, which was reported almost 20 years ago to occur in up to 80% of patients with previously normal ducts after placement of 5F polyethylene stents9; this alarmingly high incidence was recently confirmed, as was a significantly decreased risk of injury with 3F stents.10 Although it generally has been assumed that such changes are clinically silent, patients with serious and lasting consequences of pancreatic stent–induced injury have been seen at most major centers and have now been reported in a series of patients11 in whom 5F stents were placed for prophylactic purposes in community and advanced centers, and mostly the stents were in place for only a few weeks. Finally, documentation of passage or removal of stents requires Volume 71, No. 6 : 2010 GASTROINTESTINAL ENDOSCOPY
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TABLE 2. Challenges to application of prophylactic pancreatic stents Education of endoscopists regarding indications and applications Need for training in techniques of pancreatic stent placement Familiarity with specialized guidewires and pancreatic stents Enhanced understanding of pancreatic duct anatomy Practice structure to ensure stent passage or removal Awareness of potential complications
TABLE 3. Suggested indications for placement of pancreatic stents Suggested Sphincter of Oddi dysfunction (suspected or documented, regardless of manometry findings) Difficult cannulation involving pancreatic instrumentation or injection Aggressive instrumentation of pancreatic duct (eg, brush cytology) Pancreatic guidewire placement during biliary cannulation Pancreatic sphincterotomy (major or minor papilla)
Failed placement
Precut sphincterotomy starting at papillary orifice
Guidewire/stent ductal perforation
Balloon dilation of intact biliary sphincter
Inward delivery/migration Stent-induced pancreatic duct/parenchyma injury
Prior post-ERCP pancreatitis Endoscopic ampullectomy Not suggested
careful tracking of patients with imaging or endoscopic removal, a process that will occasionally fail even with the most rigorous follow-up. So, with all these caveats, is it really worth placing pancreatic stents? After all, the evidence for efficacy is now quite overwhelming. It is often said at advanced centers that routine use of pancreatic stents in high-risk cases has changed the complexion of ERCP, reducing incidence and severity of post-ERCP pancreatitis to a more acceptable level, such that pancreatitis of any severity more than mild is a rarity, even with high-risk indications such as SOD and pancreatic endotherapy (Table 3). The problem with the available data on pancreatic stents is that they are exclusively from advanced centers with highly expert endoscopists, who may disagree about details of technique but all have substantial expertise. Up until now, there have been no data on use and outcomes of pancreatic stenting in community practices. To this end, the survey published in the current issue of Gastrointestinal Endoscopy by Dumonceau and colleagues12 is particularly revealing and much needed. At a live endoscopy course, a questionnaire was administered to the attendees, who were a mix of community and tertiary-care center endoscopists from various Western European countries. The data may not represent a cross section of the larger ERCP community, as evidenced by limited participation (only 30% of participants responded) and the fact that attendance at such courses may self-select for practicing endoscopists with a higher than average commitment to therapeutic endoscopy. Notwithstanding, the authors found that less than half of the surveyed endoscopists reported attempting prophylactic pancreatic stenting in at least 75% of cases that were clearly identified as high risk and were demonstrated to benefit from pro942 GASTROINTESTINAL ENDOSCOPY
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Lower-risk patients (older or with obstructed pancreatic duct) undergoing a low-risk procedure Pancreatic duct not injected with contrast material and limited guidewire manipulation in low-risk patient Needle-knife precut or fistulotomy starting above the orifice in absence of other risks Doubtful feasibility of successful pancreatic wire access and stent placement Biliary therapy in patients with pancreas divisum
phylactic stenting, despite widespread acknowledgement of the efficacy of pancreatic stenting in the literature. Twenty-one percent of survey respondents did not perform prophylactic pancreatic stenting in any of the circumstances listed; this was mainly ascribed to lack of experience. An annual hospital volume of greater than 500 ERCPs and tracking of complication rates was independently and significantly associated with the use of prophylactic pancreatic stenting. These data represent the first attempt at a wider survey of pancreatic stent use. The available data lead to a number of questions that need answering. What is the actual prevalence of use of pancreatic stents in various communities, including in the United States? In absence of data, we are currently dependent on anecdotes. This author’s impression from informally polling audiences at regional talks in the United States and abroad is that use of pancreatic stents is increasing but inconsistent. There are some smaller hospitals at which pancreatic stenting is standard practice, yet there are even a few major centers at which pancreatic stenting is viewed as exotic. Do less-experienced endoscopists www.giejournal.org
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achieve satisfactory results with pancreatic stents? Again, anecdotes suggest that there can be major problems. We periodically see or hear of cases involving frank perforation of a pancreatic duct by a guidewire, usually a standard 0.035 variety used by an endoscopist who is wellseasoned in biliary work. At a well-established ERCP practice, a debate a few years ago focused on which end of a single pigtail pancreatic stent should be placed in the duct and which end in the duodenum. Not so surprising are the all-too-numerous cases of accidental delivery of a stent, sometimes with the entire outer pigtail pushed entirely into a small-caliber duct— or later inward migration, usually of longer, straight stents—and perhaps even more damaging, the local efforts at retrieving those “migrated” stents. Experience with retrieval of 23 such intraductal stents was recently reported from a single, concentrated tertiary-care referral center, and even there, retrieval was not always successful.13 As concerning, some of the endoscopists noted in the article by Dumonceau reported placing 7F or 10F pancreatic stents for prophylaxis, which seems excessively large and likely to cause duct injury considering that a normal pancreatic duct diameter in a young patient can be as small as 2 or 3 mm, which is approximately 6F to 9F. All of these anecdotes and limited data suggest clearly that more education in techniques and equipment for placing pancreatic stents is required before endoscopists with a background of primarily biliary therapy can begin to effectively place pancreatic stents. Rationales for not placing pancreatic stents in high-risk cases are becoming harder to find. Some endoscopists at various levels claim very low pancreatitis rates without the use of pancreatic stents. Such claims might lead one to suspect that either they are performing mostly very lowrisk cases, have an early “quit point” and lower success rates, or perhaps—as suggested by the Dumonceau study—that less use of pancreatic stents correlates significantly with absence of formal tracking of complication rates. Is it now considered “standard of care” to place a pancreatic stent during high-risk cases? Definitely the issue has come up in lawsuits, although fear of lawsuits is not the ideal driver for determining specifics of practice. The inference already has been enunciated14; the ability to reliably place a small-caliber stent in the pancreatic duct will soon become a “sine qua non” for performance of ERCP. This is especially true for cases predetermined to be at high risk before the duodenoscope is passed—such as possible SOD, ampullectomy, or acute recurrent pancreatitis— but shouldn’t this also be true for a middleaged woman with recurrent pain and abnormal liver function test results or a young woman with a bile leak after cholecystectomy for gallbladder dyskinesia? ERCP clearly may be indicated in both situations, but both easily could be considered high risk. Nowadays, many patients undergo imaging techniques such as EUS or MRCP that reveal pancreatic anatomy before ERCP is contemplated, allowing fairly precise anticipation of not only expected www.giejournal.org
Editorial
TABLE 4. Suggested areas for research Practice patterns and effectiveness of pancreatic stent placement in practice Determining safest and most effective configuration of pancreatic stents and guidewires Improved stent design/material to minimize both postERCP pancreatitis and duct injury
findings at ERCP but appropriate therapy, and remove those “borderline” indications that result in so much trouble in routine practice. However, many high-risk scenarios cannot be determined until the ERCP has begun, especially difficult cannulation. Despite years of practicing and studying ERCP, this author has not managed to reliably sort out in advance which patients with biliary obstruction will turn out to be difficult and potentially risky cases. Is pancreatic stenting for everyday practice or for experts only? Clearly, for everyday practice, but with qualifications. Endoscopists already proficient at biliary ERCP may need to “go back to school” to learn how to place pancreatic stents consistently and effectively, without causing damage in the process. Readily accessible educational resources include digital video disks (DVD) offered by the American Society for Gastrointestinal Endoscopy (www.asge.org) (including our group’s recent DVD on biliary access techniques, which includes a detailed presentation of prophylactic pancreatic stent placement) and many relevant cases on the Digital Atlas of Video Education (DAVE) project Web site (http://daveproject.org). Hands-on training is generally available in animal workshops (www.asge.org). It may be very useful for practicing endoscopists interested in expanding their expertise to observe cases at a high-volume center that routinely places prophylactic pancreatic stents on an elective basis in normal ducts, such as in patients with SOD. Until proficiency at pancreatic stenting is demonstrated, the appropriateness of conventionally indicated ERCP may be questioned in some settings. Additionally, the simple ability to place a pancreatic stent for prophylaxis does not imply the ability to perform complex pancreatic therapy, such as pancreatic sphincterotomy or stone extraction. Substantial additional research is clearly needed (Table 4). Data are needed on frequency of use of stents in practice, with success and outcomes determined by intentto-treat principles, not just for pancreatic stents but for appropriateness and outcomes of ERCP attempted in various contexts. Endoscopists must become aware of the potential hazards of pancreatic stents. Further research into best designs and materials for stents and guidewires is ongoing but should be accelerated. Then we can look forward to better outcomes for patients from ERCP. Volume 71, No. 6 : 2010 GASTROINTESTINAL ENDOSCOPY
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DISCLOSURE Dr. Freeman has received no remuneration or perquisites from Hobbs Medical Inc, direct or indirect, for development of the Freeman pancreatic stents. Dr. Freeman has received speaking honoraria and fellowship program support from Cook Endoscopy and Boston Scientific Endoscopy. Martin L. Freeman, MD Division of Gastroenterology Department of Medicine University of Minnesota Minneapolis, Minnesota, USA
4.
5.
6. 7.
8.
9. Abbreviations: SO, sphincter of Oddi; SOD, sphincter of Oddi dysfunction. 10.
REFERENCES 1. Freeman ML. Pancreatic stents for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Clin Gastroenterol Hepatol 2007;5:1354-65. 2. Ito K, Fujita N, Noda Y, et al. Can pancreatic duct stenting prevent postERCP pancreatitis in patients who undergo pancreatic guidewire placement for achieving selective biliary cannulation? A prospective randomized controlled trial [abstract]. http://www.uegf.org/publications/ abstracts2008/abstract_detail.php?aId⫽OP082&navId⫽218. 3. Sofuni A, Maguchi H, Itoi T, et al. Prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis by an endoscopic pan-
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creatic spontaneous dislodgement stent. Clin Gastroenterol Hepatol 2007;5:1339-46. Singh P, Das A, Isenberg G, et al. Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute pancreatitis? A metaanalysis of controlled trials. Gastrointest Endosc 2004;60:544-50. Das A, Singh P, Sivak MV, et al. Pancreatic-stent placement for prevention of post-ERCP pancreatitis: a cost-effectiveness analysis. Gastrointest Endosc 2007;65:960-8. Brackbill S, Young S, Schoenfeld P, et al. A survey of physician practices on prophylactic pancreatic stents. Gastrointest Endosc 2006;64:45-51. 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. Chahal P, Tarnasky PR, Petersen BT, et al. Short 5Fr vs long 3Fr pancreatic stents in patients at risk for post-endoscopic retrograde cholangiopancreatography pancreatitis. Clin Gastroenterol Hepatol 2009;7:834-9. Kozarek RA. Pancreatic stents can induce ductal changes consistent with chronic pancreatitis. Gastrointest Endosc 1990;36:93-95. Rashdan A, Fogel EL, McHenry L, et al. Improved stent characteristics for prophylaxis of post-ERCP pancreatitis. Clin Gastroenterol Hepatol 2004; 4:322-9. Bakman YG, Safdar K, Freeman ML. Significant clinical implications of prophylactic pancreatic stent placement in previously normal pancreatic ducts. Endoscopy 2009;41:1095-8. Dumonceau J-M, Rigaux J, Kahaleh M, et al. Gastrointest Endosc 2010; 71:934-9. Price LH, Brandabur JJ, Kozarek RA, et al. Good stents gone bad: endoscopic treatment of proximally migrated pancreatic duct stents. Gastrointest Endosc 2009;70:174-9. Baillie J. Endoscopic ampullectomy: does pancreatic stent placement make it safer? Gastrointest Endosc 2005;62:371-3.
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