Plastic or metal stent for benign biliary stricture?

Alexander Meining, Ulm

Endoscopy. 2015 Jul;47(7):605-10.

JAMA. 2016 Mar 22-29;315(12):1250-7.

Until only a few years ago, endoscopic therapy for benign biliary stricture involved implantation of one or multiple plastic stents, exchanged every 3 months, for a period of around 1 year [1]. However, the procedure was associated with high costs for materials and time. The results of a single-arm, multicenter study published in 2014 for the first time reported a larger series of 187 patients in whom placing a fully covered metal stent led to successful treatment for benign strictures in 75% of cases [2]. The logical implication of this finding was that a randomized study needed to be carried out to compare (plastic) multiple stenting with removable metal stents.

Two such studies have in the meantime been published: a study conducted in Finland, published in Endoscopy in 2015 and including a total of 60 patients, all of whom had benign strictures against a background of chronic pancreatitis [3]; and a US/UK study prestigiously published in JAMA in 2016, including 112 patients, most of whom had strictures after liver transplantation (65%) and only around one-third of whom had stenoses following chronic pancreatitis [4].

The results of the two studies can be summed up briefly:

The medium-term therapeutic success (1 year after removal of the stent) is around 90%, both with multiple stenting and with metal stent implantation, and the treatment thus appears to be highly effective.

The story becomes more interesting when you read the two studies carefully and analyze the details. In the Finnish study, the design was intended to show whether or not the metal stent was superior (90% vs. 60%), and only 60 patients were randomized for the purpose. With similar rates of treatment success, at 90% (plastic stents) and 92% (metal stents), the result was therefore negative. The authors explain the high rate of response to plastic stenting with the placement of up to seven 10-Fr stents, resulting in an overall diameter identical to that of a 10-mm metal stent. One case of cholecystitis occurred in each group as a side effect.

The US/UK study, by contrast, was designed as an equivalence study, but the originally planned case numbers were reduced by a “data and safety monitoring board” from 250 to 112 after an intermediate analysis! However, the study’s target of noninferiority was met after adjustment of the equivalence threshold to ± 15%. Nevertheless, if the post-transplantation cases of stricture are excluded, it only leaves 17 patients (plastic stents) versus 18 patients (SEMS) with chronic pancreatitis, or two patients with postoperative stenoses per group. No cases of cholecystitis occurred, since an intact gallbladder and/or cystic duct at or below the level of the stenosis was an exclusion criterion. Recurrent strictures were mainly noted in the patients with liver transplantation, and stent migration occurred in 13 of 14 cases in that group of patients.

What does it all mean in practice?

The evidence level for using a single metal stent instead of multiple plastic stents is only marginally increased by the two studies. The Finnish study, although it is clinically highly relevant in including only patients with chronic pancreatitis, used the “wrong” hypothesis for case number planning. The study published in JAMA included too many patients post liver transplantation and too few patients with chronic pancreatitis or strictures after cholecystectomy — although the latter two issues are probably much more important for the “average endoscopist.”

So let’s remain pragmatic:

• In patients with strictures following chronic pancreatitis, implanting a fully covered metal stent is highly effective and saves time, additional examinations, and probably money as well. In those with post–liver transplantation stenosis (if one is treating this type of patient), the metal stent may be an option, although the results are poorer.
• In patients with postoperative (post-cholecystectomy) strictures, the choice remains open, although treatment with plastic stents is probably often more useful due to the location of the stenoses (often near the hilum) and the bile duct has a normal caliber distal to the stenosis.

References

1. Costamagna G, Tringali A, Mutignani M, Perri V, Spada C, Pandolfi M, Galasso D. Endotherapy of postoperative biliary strictures with multiple stents: results after more than 10 years of follow-up. Gastrointest Endosc. 2010 Sep;72(3):551-7.
2. Devière J, Nageshwar Reddy D, Püspök A, Ponchon T, Bruno MJ, Bourke MJ, Neuhaus H, Roy A, González-Huix Lladó F, Barkun AN, Kortan PP, Navarrete C, Peetermans J, Blero D, Lakhtakia S, Dolak W, Lepilliez V, Poley JW, Tringali A, Costamagna G; Benign Biliary Stenoses Working Group. Successful management of benign biliary strictures with fully covered self-expanding metal stents. Gastroenterology. 2014 Aug;147(2):385-95.
3. Haapamäki C, Kylänpää L, Udd M, Lindström O, Grönroos J, Saarela A, Mustonen H, Halttunen Randomized multicenter study of multiple plastic stents vs. covered self-expandable metallic stent in the treatment of biliary stricture in chronic pancreatitis. Endoscopy. 2015 Jul;47(7):605-10.
4. Coté GA, Slivka A, Tarnasky P, Mullady DK, Elmunzer BJ, Elta G, Fogel E, Lehman G, McHenry L, Romagnuolo J, Menon S, Siddiqui UD, Watkins J, Lynch S, Denski C, Xu H, Sherman S. Effect of Covered Metallic Stents Compared With Plastic Stents on Benign Biliary Stricture Resolution: A Randomized Clinical Trial. JAMA. 2016 Mar 22-29;315(12):1250-7.