Tricky yet clinically important issues after biliary self‐expandable metal stent placement (2020)

In patients with malignant or benign biliary obstruction, endoscopic biliary stenting has emerged as the preferred management approach over percutaneous or surgical biliary drainage.1, 2 While the usual indications of endoscopic biliary drainage by ERCP using plastic stents, uncovered, partially covered, or fully covered self-expandable metal stents (SEMS) for distal and hilar biliary obstruction have been well described in major society guidelines, considerable variations in actual clinical practice exist in terms of stent preference and stenting technique.1-4 Due to differences in the underlying pathology and anatomy, there is often no good “one size fits all” strategy when it comes to the use of SEMS for management of malignant biliary obstruction. While uncovered SEMS is the prototypical metal biliary stent that can be applied in both distal and hilar malignant biliary obstructions, stent blockage due to tumor ingrowth may occur over time.1-4 This has led to clinical interest in using partially covered SEMS (PCSEMS) or fully covered SEMS (FCSEMS) for malignant biliary obstruction in an attempt to reduce tumor ingrowth and improve stent patency. However, despite the anticipated benefit, adverse events including stent migration, cholecystitis, and pancreatitis have been reported when FCSEMS is used for palliation of distal malignant biliary obstruction, management of benign biliary stricture, or post-operative bile leak.3, 5 To date, dedicated studies with large sample sizes to evaluate the incidence of post-ERCP pancreatitis (PEP) after FCSEMS insertion by ERCP remain limited. In this issue of the Journal, Xia et al. reported the results of a multicenter retrospective study investigating the impact of FCSEMS on the risk of PEP.6 Six hundred and two patients from five referral centers were included in the study. Indications for FCSEMS were malignant biliary obstruction (69.2%), inflammatory biliary strictures (22.3%), post-liver transplant biliary strictures (3.3%), chronic pancreatitis related biliary strictures (2.0%), and post-sphincterotomy bleeding (3.2%). Biliary sphincterotomy was performed before FCSEMS insertion in 64.3% of the patients. Prophylactic pancreatic duct stent placement or post-ERCP rectal indomethacin administration to prevent PEP was used in 25.9% and 37.5% of the patients, respectively. The overall incidence of PEP was 9.3%. In subgroup analysis of patients who did not receive prophylaxis for PEP, the incidence of PEP was up to 18.6%. In multivariate analysis, difficult cannulation (reported in 24.9% of procedures) was found to be an independent risk factor for PEP, whereas pancreatic stenting was found to be an independent protective factor for PEP. The incidence of PEP itself may be a moving target because majority of prior studies on FCSEMS did not adopt prophylaxis of PEP by pancreatic duct stenting or rectal indomethacin in the study protocol, whereas a significant portion of patients in the study by Xia et al. received pancreatic duct stenting (25.9%) and rectal indomethacin (37.5%), which may theoretically reduce the rate of PEP in this cohort. Based on the data from studies without the use of prophylaxis for PEP, the incidence of PEP after FCSEMS placement was found to range from 1.5% to 7.0% in three landmark randomized controlled studies comparing FCSEMS and uncovered SEMS in patients with distal malignant biliary obstruction and was found to be 2.7% in a large prospective international multicenter study of patients with benign biliary strictures managed with FCSEMS.5, 7-9 Interestingly, the overall incidence of PEP was relatively high at 9.3% in Xia's study despite the use of prophylaxis for PEP in more than half of the patients. In patients who did not receive PEP prophylaxis, the incidence of PEP was reported to be even higher at 18.6%. How should endoscopists interpret the results of the study by Xia et al.? First, one should recognize that the study population was rather heterogeneous since patients with biliary obstruction from both malignant and benign etiologies as well as patients with post-sphincterotomy bleeding were included. Second, it is possible that transpapillary FCSEMS insertion may not be the only contributing factor to PEP in this study and the influence by other widely accepted independent risk factors for PEP, including patient-related factors (prior PEP, female sex, younger age, suspected sphincter of Oddi dysfunction, absence of chronic pancreatitis, normal serum bilirubin, etc.), procedure-related factors (difficult cannulation, repetitive pancreatic duct guidewire cannulation, pancreatic duct contrast injection, pancreatic sphincterotomy, etc.), and operator-related factors (e.g. operator experience, case volume, and trainee participation) could not be completely excluded in this retrospective study.10 This hypothesis was further supported by the finding that difficult cannulation was significantly associated with PEP in Xia's study. When compared with biliary drainage for malignant distal common bile duct obstruction, endoscopic stenting for palliation of hilar malignant biliary obstruction is technically more challenging since patients often require multiple stents to achieve drainage of adequate liver volume.11 SEMS placement for unilateral or bilateral drainage with stent-in-stent (SIS) or stent-by-stent (SBS) configuration are considered acceptable techniques for endoscopic palliation of malignant hilar biliary obstruction in recent guidelines.1, 11 While comparative studies of SIS vs SBS SEMS configuration for bilateral drainage of malignant hilar biliary obstruction revealed similar technical success rate, clinical success rate, adverse event rate, and SEMS patency duration, less is known about the feasibility and clinical outcomes of endoscopic reintervention for clinically successful bilateral SEMS placement in patients with advanced malignant hilar obstruction.12-15 In this issue of the Journal, Lee et al. retrospectively reviewed the efficacy of endoscopic reintervention in 55 patients (SEMS configuration: SIS 48, SBS 7) with prior technically and clinically successful bilateral SEMS for malignant hilar biliary obstruction between 2014 and 2017.16 Among the 55 patients, 47 underwent primary endoscopic reintervention and 8 underwent secondary endoscopic reintervention following percutaneous transhepatic biliary drainage (PTBD). The technical success rates of primary and secondary endoscopic reintervention were 93.6% and 87.5%, respectively (P = 0.47), whereas the clinical success rates were 72.3% and 50%, respectively (P = 0.23). The median cumulative stent patency duration was 119 days for the primary reintervention group and 55 days for the secondary reintervention group (P = 0.68). When outcomes were analyzed according to primary SEMS deployment configuration, the technical success rates for SIS group and SBS group were 95.8% and 71.4%, respectively (P = 0.07), while the clinical success rates for SIS group and SBS group were 68.8% and 71.4%, respectively (P = 1.00). No meaningful predictive factor for stent patency duration-related factors after reintervention was identified in univariate and multivariate analysis. Reintervention for blocked bilateral SEMS in SIS or SBS configuration in patients with advanced malignant hilar biliary obstruction is often technically challenging. Based on studies published after 2000, the need for endoscopic reintervention after initial bilateral SEMS placement ranged from 6% to 58.3% for SIS configuration and 3% to 45% for SBS configuration.4 Success rates of reintervention were reported to range from 44.4% to 100% for SIS configuration and 25% to 92.3% for SBS configuration in five studies published between 2009 and 2013.4 Despite the promising reintervention success rates reported in this issue of the Journal by Lee et al., one should keep in mind that not all cases of malignant hilar obstruction with dysfunctional SEMS are amenable to further endoscopic therapy even in experienced centers. When further endoscopic therapy is not feasible, PTBD remains a viable option. However, in patients with terminal malignancy, reintervention for recurrent SEMS dysfunction may not be desirable from a quality of life standpoint, and a more palliative approach should be considered. In summary, endoscopic management of biliary obstruction by SEMS is both a science and an art in clinical practice. Becoming familiar with the strengths and the potential limitations of various SEMS types and stenting techniques would empower endoscopists to provide the optimal biliary drainage strategy tailored to patient's need.