Fully covered metal stents in the pancreatic duct: balancing trade-offs
Article Outline
Abbreviation: FCSEMS, fully covered self-expandable metal stent
Clinical experience has shown that pain from chronic pancreatitis can be relieved by main pancreatic duct stenting when obstruction is caused by a dominant stricture. However, despite the use of pancreatic stents for over 2 decades, the optimal strategy for the treatment of benign strictures remains undefined. There have been no randomized trials comparing stent sizes, stent designs, interval of stent exchanges, or duration of stenting. Consequently, a standardized strategy is lacking and approaches vary widely from center to center.
Lacking data to guide management of pancreatic duct strictures, can we extrapolate from our experience with stenting of benign bile duct strictures? In the bile duct, bigger has been found to be better. Encouraged by the favorable results when using the combined diameter of multiple plastic stents to maximize dilation of benign bile duct strictures,1 the Rome group applied the same strategy in the pancreatic duct. A mean of 3 plastic prostheses ranging in size from 8.5F to 11F were implanted for a mean of 7 months in 19 patients.2 All patients had pain resolution during the stenting period, and the strictures resolved in 18 of the 19 patients after stent removal. At a mean follow-up of 38 months, only 2 patients (10.5%) had recurrent symptomatic strictures.
If bigger is better, then what about temporary placement of a fully covered self-expandable metal stent (FCSEMS)? The University of Virginia group used an FCSEMS in 44 patients with benign biliary strictures, left in situ for a median of 3.3 months.3 Strictures resolved in 83% of cases. Translating this experience to the pancreatic duct, the same group implanted FCSEMSs for a mean of 3 months in 5 patients with symptomatic benign pancreatic duct strictures.4 All had pain relief, but 3 out of the 5 patients developed recurrent strictures after removal of the FCSEMS.
In 2008 the Ascan Medical Center group in Seoul used FCSEMSs to treat refractory benign pancreatic strictures in 13 patients.5 The stents were left in situ for 2 months. All patients had pain relief and a statistically significant improvement of strictures coupled with reduction of upstream dilation. However, there was a high stent migration rate of 39%, including one proximal migration. Of note, the design of the FCSEMS used in that study was different from that used in the University of Virginia group study, particularly in lacking “anchoring fins.”
In this issue of Gastrointestinal Endoscopy, the Ascan Medical Center group report on an “antimigration” modification of the FCSEMS design used in their previous study.6 Two features that were added were (1) a flaring of the ends; and (2) the use of different mesh cell sizes (“bumpy” design) that impart different segmental radial forces. A polytetrafluoroethylene coating with properties of “high conformability” was used for all but the flared stent ends, which required silicone.
The “antimigration” FCSEMS design was implanted in 32 symptomatic chronic pancreatitis patients with dominant strictures. Pain resolved in all cases, and follow-up ERCP 3 months after stent placement showed resolution of ductal strictures in all cases. Migration did not occur in a single patient over the 3-month implant period. However, there was an apparent trade-off: De novo strictures occurred in 5 patients (16%). An example of such a stricture is provided in Figure 4D of their article. Such strictures complicating FCSEMS placement were not observed in the group's previous study.
What is the clinical significance of these de novo strictures, and need we be concerned? The authors state that the patients were asymptomatic, but follow-up was short and the natural history of the strictures unknown. The authors re-treated 4 of the 5 patients with de novo strictures with an additional 2-month placement of a longer stent after balloon dilatation. After removal of the longer stents, the strictures were reported on radiologic study to have resolved. Pancreatoscopy to document stricture resolution was not done. No follow-up data were provided for this cohort of 4 patients with re-treated strictures.
A complication that resembles the very condition to be treated deserves further investigation. The site of the strictures correlated with the position of the intraductal flared end of the stent (as seen in Fig. 4D of the article), and the authors postulated that the excessive radial force of the ends was the cause of injury. We have seen a similar effect of ulceration, hyperplastic tissue growth, and stricturing at the stent ends after placement of endoluminal stents. The flaring of the stent ends per se is probably not the cause of structuring, but rather the disproportionately greater stent diameter relative to the native lumen diameter. Strictures have been observed to occur after implantion of FCSEMSs without flared ends into the bile duct.7
The risk of de novo strictures raises questions regarding the optimal duration of stenting using FCSEMSs. Adequate remodeling and recanalization of the pancreatic duct must be weighed against the risk of stricture formation. Of note, the Ascan group extended the duration of FCSEMS placement from 2 months in their previous study to 3 months in the current study. The reason for this change in protocol is not explained. Needless to say, randomized trials to determine the optimal duration of FCSEMS stenting are needed.
Surprisingly, there are no animal studies investigating the use of any type of FCSEMS in the pancreatic duct. There is only one published animal study reporting on uncovered SEMSs in the pancreatic duct.8 Investigating radiologic and histologic changes in the pancreatic duct and parenchyma after placement of metallic stents in 8 normal dog pancreatic ducts, Yamakado et al8 found that ductal strictures (n = 4) and occlusions (n = 2) occurred at the edge of the initially stent-implanted region, associated with dilation of the duct upstream at 1 month or later. Epithelial hyperplasia was observed at the sites of ductal stricture and occlusion. We need to know if FCSEMSs cause similar tissue effects that can result in stricturing at the stent edges. Tissue overgrowth at the stent ends may be an inherent limitation of all SEMSs, whether covered or uncovered.
There are other questions that should be addressed in well designed animal studies before implanting FCSEMSs in our patients. What are the ramifications of placing an FCSEMS in a duct that receives numerous tributaries from an extensive system of secondary and tertiary branches? Common sense dictates that at least some of the side branches will not drain and patients will suffer negative sequelae, including worsening of residual pancreatic exocrine function. Overt clinical complications related to side-branch blockage were not reported in either of the Ascan group's studies, but this probably relates more to the “forgiving” effect of end-stage chronic pancreatitis. We must guard against indiscriminate use of FCSEMSs in patients with earlier-stage chronic pancreatitis, or any other causes of pancreatic strictures.
At what point should we consider using an FCSEMS? Past studies have targeted patients with “refractory” strictures, which implies either failure of the standard therapy using plastic stents or recurrence after removal of plastic stents. How long to stent has been controversial, but the general consensus has been to stent for ≥12 months before declaring a stricture to be “refractory.” In the previous (pilot) study by the Ascan group, only patients with persistent painful strictures after >12 months of plastic stenting were included. Furthermore, criteria for a “refractory” stricture included persistence of contrast medium in the dilated upstream duct of the body and tail for >5 minutes after stent removal. In the current study, the group lifted the restriction to patients with “refractory” strictures and included patients with recurrent or persistent painful stricture after previous placement of pancreatic plastic stents for ≥2 months. This change in inclusion criteria disqualifies any meaningful “apples-to-apples” comparison of the results of the current study with the previous one. It is conceivable that a stricture treated for a shorter period of time with fewer plastic stent exchanges will be “tighter,” and therefore a metal stent would be less prone to migrate after implantation. It is disturbing that the Ascan group lowered their threshold to use FCSEMSs for the treatment of painful chronic pancreatitis without first establishing their safety and efficacy in patients with refractory strictures.
Recent pilot study publications reporting on the use of FCSEMSs for benign indications in the bile duct will no doubt lead to their expanded use for benign disease.7, 9, 10 However, we must be cautious that this is not prematurely applied to the pancreatic duct. The management of strictures in the bile and pancreatic ducts—both resulting from chronic pancreatitis—are very different; the indication for treatment in the former is stricture resolution (restoration of bile flow), and in the latter it is pain relief. It is noteworthy that the majority (59% to 73%) of patients with severe chronic pancreatitis who underwent plastic stenting and responded to treatment showed a long-term (27 to 46 month) sustained clinical improvement after definitive plastic stent removal, and pain relief was not always associated with stricture resolution.11, 12, 13 The presense of pancreatic stones and treatment with extracorporeal shockwave lithotripsy (ESWL) also may influence the response to endoscopic intervention. In the current Ascan study, 26 out of 32 patients (81%) had obstructive pancreatic stones, and among them 73% (19 out of 26) underwent ESWL.
The bile and pancreatic ducts ducts are not created equal, so neither should the stents that we insert in them be. The Ascan group has reported about a novel FCSEMS tailored to the unique anatomy of the pancreatic duct. The “antimigration” modification appears to have solved the problem of stent migration observed in the group's previous study. The results reported in the current series are encouraging, but the follow-up was short, and safety and benefit must be judged in the context of long-term data. Far too little is known about the incidence and types of complications related to FCSEMSs for the treatment of strictures of chronic pancreatitis. For the present, we should exercise caution and reserve FCSEMSs for patients meeting strict inclusion criteria in prospective outcome trials.
References
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DISCLOSURE: The author disclosed no financial relationships relevant to this publication.
PII: S0016-5107(10)01341-6
doi:10.1016/j.gie.2010.03.1064
© 2010 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.
Refers to article:
- Modified fully covered self-expandable metal stents with antimigration features for benign pancreatic-duct strictures in advanced chronic pancreatitis, with a focus on the safety profile and reducing migration , 21 May 2010
