Benign biliary strictures: how we are evolving to the perfect endoscopic strategy

 

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Anastomotic biliary strictures are the most common biliary complication of orthotopic liver transplantation. They occur frequently, with a reported incidence of 5 % – 30 % [1]. Endoscopic therapy is accepted as first-line treatment with the classic approach being multiple plastic stent (MPS) placement, balloon dilation, or a combination of these two techniques. The role of single plastic stents is now obsolete, as shown by van Boeckel et al., who published an excellent and comprehensive review that showed the limitation of single plastic stents for benign biliary strictures (BBS) [2]. The durability of single plastic stents is poor, and the adverse events are unacceptably high. Hence, single plastic stent intervention should only be used as an initial approach in very selected cases prior to engaging definite strategies.

“Current studies using metal stents for AS use a 3 month placement; however, longer treatment times may be superior, as seen in cases of chronic pancreatitis where stents are placed for 12 months.”

Recently, endoscopic management has evolved with the increased use of self-expandable metal stents (SEMS), with the premise of requiring fewer sessions of endoscopic retrograde cholangiopancreatography (ERCP) and shorter duration of therapy. Despite an emerging literature supporting the use of fully covered SEMS (FCSEMS), the most concerning complication remains stent migration [3]. Traditional metal stent designs seem to have poor durability in anastomotic biliary strictures after orthotopic liver transplantation, whereas newer intraductal FCSEMS with retrieval strings have been developed and show promise in avoiding migration in anastomotic strictures [4].

In this issue of Endoscopy, Tarantino et al. report a prospective evaluation of a modified MPS protocol in patients with post liver transplant anastomotic strictures [5]. The standard MPS protocol was varied to eliminate the exchange of old stents with new stents. The study explores the practice of introducing additional stents alongside existing stents during pre-arranged ERCPs at 3-monthly intervals. Excellent stricture resolution rates of 99 % were achieved, which is in the higher range of previously reported studies. The long-term follow-up of 993 days reported recurrence rates of only 8 %. Importantly, the procedure was well tolerated with few (8 %) complications reported. Interestingly, despite the predetermined 12-month treatment protocol, the median endotherapy time was 8 months. The mean number of ERCP procedures was 4.7, suggesting patients may achieve these excellent outcomes in a shorter time frame than the gold-standard 12-month endotherapy time. It also suggests that interval ERCPs were less than 2 months apart, which is more frequent than most protocols using MPS.

Developing an optimal endoscopic therapy for BBS is limited by two key issues. First, there is no accepted classification for BBS. The bismuth classification for malignant biliary strictures is highly relevant for all malignant hilar strictures. The classification helps differentiate outcomes in clinical studies and assists in making important decisions regarding planning interventions such as unilateral vs. bilateral stenting. This contrasts with the bismuth classification for post-surgical BBS, which has no applicability to current endoscopic interventions [6]. This classification is rarely used in deciding etiology or management strategies for the endoscopist. Hence, a new classification is needed, with the rationale of allowing for a common understanding to direct clinical research and report outcomes in a fashion similar to the malignant biliary obstruction literature. In 2015 we proposed a classification to allow for clarity in diagnosis and management of BBS [7]. In this classification there are four types of strictures. Type 1 strictures are in the distal common bile duct (CBD), such as in chronic pancreatitis. Type 2 strictures are in the upper CBD or common hepatic duct, such as anastomotic stricture or post cholecystectomy strictures. Type 3 strictures are intrahepatic including the hilum, such as in primary sclerosing cholangitis, and type 4 are surgical anastomoses such as hepaticojejunostomy. Many clinical studies using stenting do not differentiate outcomes based on the level of the stricture and often include type 1 and 2 strictures. Outcomes in such studies vary between stricture types [3].

Another key issue that is not well addressed in clinical studies is the variation in the designs of metal stents. Traditional FCSEMS types have been extensively studied, and in a large multinational study by Devière et al. [3], it is suggested that these types of stents are more suited to distal strictures associated with chronic pancreatitis (type 1). In this study it was shown that these stents perform poorly for cholecystectomy and anastomotic strictures (type 2), and should probably be avoided in these indications due to excessive migration and recurrence of strictures. Migration issues may be circumvented with new intraductal stents [8], as these stents sit entirely within the bile duct and have a long suture-like string, which sits in the duodenum for accessibility. Intraductal stents seem to have the lowest migration rates and excellent performance characteristic for type 2 strictures. The reported migration rates are usually < 10 % (compared with > 30 % for traditional stents), except for one study reporting migration at 19 % [9].

Moving forward, we need to consider which end points should be the ideal targets for future studies. Current evidence for all described interventions shows a very high stricture resolution rate and so this end point may be currently optimal. Recurrence remains an issue and may be improved by reducing problems such as metal stent migration, which would allow for longer in situ placement and fibrous tissue remodeling. The optimal time for metal stent placement is one key area that needs further investigation. Current studies using metal stents for AS use a 3 month placement; however, longer treatment times may be superior, as seen in cases of chronic pancreatitis where stents are placed for 12 months. This length of stenting may also explain the benefits seen with the MPS protocol, which treats strictures for 12 months.

Reducing the burden of ERCPs in MPS protocols is also a target for study. This can be achieved by reducing procedure numbers over the 12-month treatment time or even reducing the complexity of intervention during ERCP, and preferably both. The study by Tarantino et al. addresses the latter issue, as insertion of an additional stent without removal and reinsertion of multiple stents simplifies the process. Future studies using similar protocols could examine less frequent ERCPs over this 8-month treatment time to further reduce the impact on these patients and on health care costs. The strategy that will eventually prove to be the optimum or preferred approach will depend upon high quality prospective randomized studies.

• References

• 1 Chan CH, Telford JJ. Endoscopic management of benign biliary strictures. Gastrointest Endoscopy Clin N Am 2012; 22: 511-537
  CrossrefPubMedGoogle Scholar
• 2 van Boeckel P, Vleggaar FP, Siersema PD. Plastic or metal stents for benign extrahepatic biliary strictures: a systematic review. BMC Gastroenterol 2009; 9: 96
  CrossrefPubMedGoogle Scholar
• 3 Devière J, Reddy DN, Püspök A. et al. Successful management of benign biliary strictures with fully covered self-expanding metal stents. Gastroenterology 2014; 147: 385-395
  CrossrefPubMedGoogle Scholar
• 4 Kaffes A, Griffin S, Vaughan R. et al. A randomized trial of a fully covered self-expandable metallic stent versus plastic stents in anastomotic biliary strictures after liver transplantation. Therap Adv Gastroenterol 2014; 7: 64-71
  CrossrefPubMedGoogle Scholar
• 5 Tarantino I, Amata M, Cicchese N. et al. Sequential multistenting protocol in biliary stenosis after liver transplantation: a prospective analysis. Endoscopy 2019; 51: 1130-1135
  Article in Thieme ConnectPubMedGoogle Scholar
• 6 Bismuth H. Postoperative strictures of the biliary tract. In: Blumgart LH. The biliary tract. Clinical Surgery International series, vol. 5. Edinburgh: Churchill Livingstone; 1982: 209-218
  Google Scholar
• 7 Kaffes AJ. Management of benign biliary strictures: current status and perspective. J Hepatobiliary Pancreat Sci 2015; 22: 657-663
  CrossrefPubMedGoogle Scholar
• 8 Aepli P, St John A, Gupta S. et al. Success and complications of an intra-ductal fully covered self-expanding metal stent (ID-FCSEMS) to treat anastomotic biliary strictures (AS) after orthotopic liver transplantation (OLT). Surg Endosc 2017; 31: 1558-1563
  CrossrefPubMedGoogle Scholar
• 9 Moon J, Choi H, Koo H. et al. Feasibility of placing a modified fully covered self-expandable metal stent above the papilla to minimize stent induced bile duct injury in patients with refractory benign biliary strictures. Gastrointest Endosc 2012; 75: 1080-1085
  CrossrefPubMedGoogle Scholar