Pancreatic stent placement for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: do we need further evidence? No, the defense rests

The exact mechanisms that contribute to the development of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) have not been fully elucidated. However, several factors are known to promote PEP, the most important of which appears to be manipulations of the ampulla, which result in decreased outflow of secretions through the main pancreatic duct, either by inducing sphincter of Oddi spasm or by causing mechanical obstruction by edema formation. The latter concept is supported by data suggesting that a patent minor papilla in the absence of pancreas divisum is protective against PEP [1], presumably because pancreatic drainage can be sustained in the face of relative obstruction at the level of the major papilla. Thus, the idea of placing a temporary pancreatic duct stent to prevent PEP is supported by its role in maintaining the integrity of pancreatic outflow.

The concept that stent placement in the pancreatic duct may reduce the risk of PEP was introduced in the early 1990s [2], and the first randomized trial to demonstrate its efficacy was shown by Tarnasky et al. [3] in patients with known or suspected sphincter of Oddi dysfunction (SOD), a group deemed to be at especially high risk for PEP due to increased pancreatic duct sphincter hypertension. Since that time a number of studies have shown that pancreatic duct stents are effective in preventing PEP, not only in patients with SOD but also in a subset of individuals found to be at high risk for PEP due to one of the following technical risk factors: difficult biliary cannulation, multiple pancreatic duct injections, precut sphincterotomy (particularly when the cut involves the papillary orifice), pancreatic duct sphincterotomy (both major and minor, the latter in the setting of pancreas divisum), pancreatic duct brush cytology, balloon dilation of the papilla for stone extraction (without biliary sphincterotomy), and endoscopic ampullectomy.

Temporary pancreatic duct stent placement for prevention of PEP in high risk patients is recommended by ERCP experts and has been included as a grade A recommendation in a 2010 guideline for PEP prophylaxis by the European Society of Gastrointestinal Endoscopy [4]. Thus, it appears that the practice of pancreatic duct stent placement is now firmly accepted in the academic domain although there remains a discrepancy as it has yet to gain widespread acceptance in the community [5]. The question remains: do we still need more evidence? In this month’s issue of Endoscopy, Mazaki et al. [6] publish the latest systematic review and meta-analysis of randomized controlled trials evaluating pancreatic duct stent placement vs. no stent placement for PEP prophylaxis. Eight studies were identified involving a total of 680 patients, 336 of whom had a pancreatic duct stent placed. The majority of patients were deemed to be at high risk although two studies enrolled patients who were not considered high risk by most criteria. Overall, 19 % in the no-stent group developed PEP compared with only 6 % in the stent group; the relative risk reduction was calculated to be 0.32 (95 % confidence interval 0.19 – 0.52; P < 0.001). Although no significant heterogeneity was found between studies (χ² = 4.09; P = 0.77; I² = 0 %), it is important to note that among these studies there were differences in the type of stent placed (i. e. length, diameter, material, and number of flanges); the duration of stent placement also varied (i. e. from 1 to 14 days post-ERCP). Interestingly, the protective effect of pancreatic duct stent placement was observed in both high risk and “mixed case” groups. In addition, there was a reduction in mild and moderate pancreatitis but not severe pancreatitis. This is in contrast to other studies in which pancreatic duct stent placement virtually eliminated severe PEP [7] [8]. Although a variety of adverse events related to pancreatic duct stents are listed in the article by Mazaki et al. [6], many are probably not direct effects of pancreatic duct stent placement but due instead to the procedure itself.

Based on this meta-analysis [6] and those previously published [9] [10], it appears that there is enough evidence to support the use of pancreatic duct stents for prevention of PEP in high risk patients and we feel that further trials are no longer necessary to adopt this practice. However, future studies will be necessary to demonstrate whether the risk-to-benefit ratio will continue to favor placement of pancreatic duct stents for PEP in non-expert endoscopy practices given that they are underutilized in the community [5] and have their own complication rates. Trauma at the level of the pancreatic duct orifice or within the duct itself may be incurred during attempted placement and, if unsuccessfully placed, can result in an even higher risk of PEP [11] and thus offset any potential benefit the stent may have had in PEP prevention. In addition, inadvertent placement of small-caliber stents completely within the main pancreatic duct or proximal migration of an appropriately placed stent can be difficult to manage [12]; long-term complications may arise from stents that cannot be easily removed, and in some cases surgery may be necessary for removal.

What is unknown and unlikely to be answered, because of difficulties with both study design and numbers needed to treat to demonstrate significant differences in rates of PEP, include optimal duration of stent placement, timing of stent placement (i. e. early vs. at the end of the procedure), and stent length, diameter [13], and configuration. Such differences may have a long-term effect due to ductal damage despite an otherwise uncomplicated pancreatic duct stent placement [14] [15] [16]. Other questions that remain to be answered include whether pancreatic duct stent placement is superior to pharmacotherapy for prevention of PEP, whether there is a synergistic effect of pharmacotherapy and pancreatic duct stent placement for PEP prophylaxis, and whether a beneficial effect of pancreatic duct stent placement remains when wire-guided techniques are utilized to increase the success rate of biliary cannulation while reducing the incidence of PEP. Additional studies are also needed to determine whether there is any role for pancreatic duct stent placement in patients considered to be at low risk for PEP.

At the present time, we believe the evidence is clear that temporary placement of prophylactic pancreatic duct stents is currently the best method for preventing PEP in high-risk patients when performed by expert hands. Additional studies are still required to refine the nuances of pancreatic duct stent placement for PEP and to determine whether the same benefit exists when pancreatic duct stents are used in the community setting. The defense rests.

Competing interests: None

References

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