Results of endoscopic treatment of recurrent malignant biliary obstruction in patients with self-expanding metal stents

Results of endoscopic treatment of recurrent malignant biliary obstruction in patients with self-expanding metal stents | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Results of endoscopic treatment of recurrent malignant biliary obstruction in patients with self-expanding metal stents Lara Meireles Azeredo Coutinho Machado, Bruno Costa Martins, Marcelo Simas Lima, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4951976/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Jan, 2025 Read the published version in Digestive Diseases and Sciences → Version 1 posted 9 You are reading this latest preprint version Abstract Background and Aim: Endoscopic biliary drainage with placement of a self-expanding metal stent (SEMS) is the preferred palliative treatment of malignant biliary obstruction. Recent advances in the treatment have prolonged survival, thus increasing the chance of recurrent biliary obstruction (RBO) after SEMS placement. The aim of this study was to compare different endoscopic approaches in patients with a SEMS and RBO, regarding clinical success and time to RBO. Methods This retrospective study included all patients with a SEMS placed because of malignant biliary strictures who underwent endoscopic retrograde cholangiopancreatography between January 2011 and December 2018. We evaluated the results of different endoscopic interventions to RBO, including insertion of a new SEMS, stent cleaning, and insertion of a plastic stent (PS). Results From January 2011 to December 2018, 70 (22.4%) patients developed RBO requiring endoscopic reintervention ( n = 105 sessions). From the 105 ERCPs, technical success, clinical success and adverse events rates were 91,4%, 71,8%, 7,8%, respectively. Younger age (OR = 1.11 95%CI: 1.03–1.19) and the finding of a patent SEMS (OR = 0.17 95%CI: 0.04–0.08) were predictors of clinical failure ( P = 0.006 and P = 0.024, respectively). The mean patency time (in days) after endoscopic reintervention was greater for SEMSs than for PSs (417.2 [95% CI: 250.0–584.4] vs 175.2 [95% CI: 124.0–226.5], P = 0.002). Conclusions Correct identification and treatment of the causal factor of RBO typically leads to technical and clinical success. Placement of a second SEMS provides longer patency compared to a plastic stent if ingrowth (overgrowth) occurs. Biliary tract neoplasms Cholestasis Self expandable metallic stents Cholangiopancreatography endoscopic retrograde Jaundice obstructive Figures Figure 1 Figure 2 Introduction Endoscopic biliary drainage with self-expanding metal stent (SEMS) placement is the palliative strategy of choice in patients with malignant biliary obstruction due to unresectable neoplasia ( 1 – 6 ). Several randomized studies and meta-analyses showed that a SEMS is superior to a plastic stent (PS) in terms of patency and survival time, reducing the risk of cholangitis and endoscopic reintervention ( 7 – 12 ). Recent advances in the treatment of unresectable malignant pancreatobiliary diseases have increased patient survival, thus increasing the prevalence of recurrent biliary obstruction (RBO) in patients with a SEMS ( 2 , 13 ). Studies indicate that SEMS dysfunction occurs in 5–40% of such patients ( 2 , 14 – 16 ). The causes of RBO include tumor ingrowth (overgrowth), sludge formation, food impaction, primary gallstones and stent migration among others. In cases of RBO after SEMS, the best endoscopic strategy is unclear. The SEMS can be cleaned mechanically with a balloon catheter, a PS or a new SEMS can be inserted within the previous stent. Other less common approaches include replacing the SEMS and radiofrequency ablation (RFA) ( 17 ). Only a few studies have compared the various approaches of RBO ( 1 , 3 , 14 , 18 – 24 ). Although some strategies have been devised, there is no consensus regarding the best management of an occluded SEMS. The European Society of Gastrointestinal Endoscopy recommends that SEMS dysfunction should be managed by placing a new PS or SEMS, without making a distinction between the two ( 4 ). In a consensus statement, experts in interventional endoscopy in Asia proposed that the therapeutic approach to patients with RBO should be customized depending on the etiology and severity of the obstruction ( 5 ). In another consensus statement regarding RBO, from Japan, stent cleaning was described as ineffective and the insertion of a second SEMS would lead to greater patency in comparison with the insertion of a PS ( 6 ). Therefore, given the lack of a consensus in the literature regarding the approach to RBO, the management of SEMS dysfunction merits investigation. The present study aimed to compare the results of different endoscopic approaches in patients with SEMS and RBO. The primary outcomes were clinical success and time to a new biliary obstruction. Patients and methods This was an observational study including all patients with a SEMS for the treatment of malignant strictures, who underwent reintervention with endoscopic retrograde cholangiopancreatography (ERCP) to investigate RBO between January 2011 and December 2018 at the Cancer Institute of the University of São Paulo (ICESP), São Paulo, Brazil . This study was approved by our institution Research Ethics Committee (Reference no. 4.995.272). Inclusion criteria were patients with a SEMS placed because of malignant biliary strictures who underwent ERCP to investigate and treat recurrent biliary obstruction. Exclusion criteria were patients lost to follow-up after the insertion of the first SEMS. The sample selection process is shown in Fig. 1 . The indications for reintervention with ERCP were recorded and categorized as: recurrence of cholestasis; cholangitis; dilation of the biliary tree; or other. All procedures were performed in the Endoscopy Unit of our institution. During ERCP, the cause of the obstruction was identified and noted as follows: ingrowth; overgrowth; biliary sludge/gallstones or stent migration. The endoscopist intervened based on the cause of obstruction identified during ERCP. The expected procedures for treating RBO were the insertion of a PS or a second SEMS within the primary stent; mechanical cleaning of the SEMS with a balloon catheter and/or Dormia basket. In each reintervention, the choice between a PS and a SEMS was left at the discretion of the endoscopist. Definitions The definitions adopted in this study were based on the Tokyo criteria, updated in 2024 ( 26 ). Clinical success was defined as a reduction of at least 50% or normalization in the bilirubin level within the first 14 days after stent placement. Time to RBO was defined as the time between endoscopic reintervention and the new obstruction. Occlusion of a SEMS or PS was defined by biochemical evidence of cholestasis, accompanied by biliary dilation on imaging studies, together with endoscopic findings consistent with occlusion. Ingrowth was diagnosed when cholangiography demonstrated a persistent biliary stricture within a covered or uncovered SEMS (CSEMS or UCSEMS, respectively) after the bile duct had been cleaned. Similarly, overgrowth was diagnosed when there was persistent stenosis at the proximal or distal ends of the SEMS. Stent migration was defined as RBO caused by complete or partial (proximal or distal) stent migration. Technical success was defined as resolution of the cause of the obstruction with free flow of contrast under cholangiography. Cholangitis were defined according to the 2018 Tokyo Guidelines ( 27 ), as signs of systemic inflammation, cholestasis, or imaging examinations showing bile duct obstruction. Adverse events were defined according to the 2024 Tokyo criteria ( 26 ), as RBO, pancreatitis, cholangitis, cholecystitis, bleeding, perforation or any other complication related to the placement of the stent in the bile duct. Statistical analysis Categorical variables were expressed as absolute and relative frequencies, whereas numerical variables were expressed as descriptive statistics (mean, standard deviation, range, median, and quartiles). For comparisons between categorical variables, we used the chi-square test (or Fisher’s exact test in the case of small samples). For comparisons of means, we used Student’s t-test for independent samples. We used generalized estimating equations (GEEs) to evaluate the simultaneous effects that demographic and clinical characteristics had on clinical success. We used Kaplan–Meier curves to analyze survival to endoscopic reintervention or death. Survival functions were compared by the log-rank (Mantel–Cox) test. Because more than one approach could be taken in each patient, frailty models were used. For the time to RBO, the Cox competing-risks model (Fine–Gray model) was used (the survival function was expressed as the subhazard ratio - SHR). Variables significant at 20% in the univariate analysis were selected for inclusion in the initial multivariate models. Variables that were not significant at 5% were then eliminated one by one in order of significance (backward elimination). In our exploratory analyses, reinterventions were evaluated as independent events. For all statistical tests, we adopted a significance level of 5%. Statistical analyses were performed with the IBM SPSS Statistics software package, version 20.0 (IBM Corp., Armonk, NY, USA) and Stata software, version 12.0 (Stata Corp LP, College Station, TX, USA). Results Between January 2011 and December 2018, 312 patients underwent endoscopic SEMS insertion for the treatment of biliary obstruction at our institution. Of those, 71 (22.7%) developed RBO and required endoscopic reintervention. One patient was lost to follow up and was excluded of the analysis. The mean age was 61.3 ± 13.3 years, and 37 patients (52.9%) were men. The majority of patients had a good performance status (ECOG 0–2 in 70% of the patients), had previously undergone chemotherapy (89.7%) and had distal biliary obstruction (78.6%). Demographic and clinical characteristics are shown in Table 1 . Table 1 Demographic and clinical characteristics of the patients Characteristic ( N = 70) Sex, n (%) Female 33 (47.1) Male 37 (52.9) Age* (years) Mean ± SD 61.3 ± 13.3 Median (range) 61.0 (28.0–88.0) ECOG performance status, n (%) 0 11 (15.7) 1 24 (34.3) 2 14 (20) 3 16 (22.9) 4 5 (7.1) Treatment prior to ERCP, n (%) None 7 (10.3) Chemotherapy only 53 (77.9) Chemotherapy and radiotherapy 8 (11.8) No information available 2 (2.8) Obstruction topography, n (%) Hilar 15 (21.4) Distal 55 (78.6) SD, standard deviation; ECOG, Eastern Cooperative Oncology Group; ERCP, endoscopic retrograde cholangiopancreatography. *At ERCP. The main cause of RBO was ingrowth occurring in 65 procedures (63.7%), followed by sludge/gallstones in 14 procedures (13.7%). The reintervention involved PS insertion in 38.4%, SEMS insertion in 30 (28.8%) and stent cleaning in 23 (22%). In 9 cases, no obstructive factor was seen and thus no endoscopic reintervention was performed. In one case, the stent was only repositioned; in another, the existing SEMS was removed, and no further action was taken (Table 2 ). Table 2 Characteristics of the endoscopic reinterventions Characteristic ( N = 105) Main ERCP finding (cause of RBO), n (%)* Ingrowth 65 (63.7) Gallstone(s)/debris 14 (13.7) Proximal migration of the SEMS 3 (2.9) Absence of obstructive factors 9 (8.8) SEMS not found † 8 (7.8) Overgrowth 3 (2.9) Endoscopic reintervention, n (%) ‡ PS insertion 40 (38.4) SEMS insertion 30 (28.8) Stent cleaning 23 (22.0) None 9 (8.7) Stent repositioning 1 (1.0) PS removal 1 (1.0) Number of reintervention, n (%) 1st 50 (71,4) 2nd 11 (15,7) 3rd 6 (8,6) > 4th 3 (3.2) ERCP, endoscopic retrograde cholangiopancreatography; RBO, recurrent biliary obstruction; SEMS, self-expanding metal stent; PS, plastic stent. *Data available for only 102 procedures. † Due to duodenal stenosis. ‡ Data available for only 104 procedures. Fifty patients underwent only one reintervention and 20 required more than one resulting in a total of 105 ERCP sessions for maintaining stent patency Technical success and Clinical success Technical success was achieved in 91.4% of the 105 interventions. Causes of technical failure occurred in five patients with duodenal obstruction, which prevented endoscopic access to the bile duct. Clinical success was achieved in 71.8% of the 105 interventions. As shown in Table S1 , clinical success was not associated with the endoscopic approach, ECOG performance status or prior chemotherapy/radiotherapy. Of nine ERCPs in which no action was taken (because the stent was found to be well positioned and unobstructed), 67% had clinical failure and the risk of death was approximately 4 times higher in these patients (HR: 3.94; 95% CI: 1.57–9.92; P = 0.004). In the multivariate analysis (Table 3 ), younger age ( P = 0.006), no reintervention ( P = 0.024), and shorter time to RBO ( P = 0.008) were predictors of the clinical failure. The chance of clinical success was 83% (1-0.17) lower in patients who underwent no reintervention than in patients who underwent any reintervention (OR = 0.17; p = 0.024). When the time to RBO between reinterventions was longer, the odds of clinical success of that intervention was higher (OR: 1.007; 95% CI: 1.002–1.013; p = 0.008). However, the number of reinterventions did not impact on the odds of clinical success. Table 3 Results of final logistic regression model for the predictors of clinical success Variable Initial model* Final model † Adjusted OR (95% CI) P Adjusted OR (95% CI) P Age (years) 1.05 (1.01–1.09) 0.026 1.11 (1.03–1.19) 0.006 Obstruction topography Hilar 0.32 (0.09–1.18) 0.086 - - Distal (reference) Endoscopic reintervention None 0.10 (0.02–0.51) 0.005 0.17 (0.04–0.80) 0.024 SEMS insertion 1.14 (0.32–3.99) 0.841 1.27 (0.41–3.92) 0.677 Stent cleaning 0.45 (0.10–2.07) 0.304 0.65 (0.19–2.24) 0.499 Other reinterventions ‡ (reference) Number of reinterventions (1 - reference) 2 0.93 (0.30–2.92) 0.900 - - 3 0.81 (0.15–4.37) 0.810 - - 4 1.15 (0.36–3.73) 0.811 - - 5 0.65 (0.23–1.84) 0.412 - - 6 (1) § - - - Adverse events 0.90 (0.14–5.84) 0.911 - - Time to RBO (days) 1.007 (1.001–1.013) 0.013 1.007 (1.002–1.013) 0.008 SEMS, self-expanding metal stent; RBO, recurrent biliary obstruction * N = 96 reinterventions in 59 patients. † N = 102 reinterventions in 70 patients. ‡ PS insertion, PS removal, and stent repositioning. § Absence of clinical failure. Recurrent biliary obstruction The mean and median stent patency after endoscopic reintervention were 252.8 days (95% CI: 186.8–318.9) and 122.0 days (95% CI: 87.6–156.4), respectively. Time to RBO was longer in patients treated with SEMS compared with PS ( p = 0.002, Table 4 ). UCSEMSs were comparable to CSEMSs ( P = 0.546) and both were superior to PS (Table S2). Figure 2 shows the cumulative patency by stent type. Table 4 Results of the post-reintervention patency analysis Variable Cumulative time to RBO (%)* P † 15 days 1 month 3 months 6 months 1 year Total (n of interventions) 91.60 ± 2.15 88.29 ± 2.53 69.44 ± 3.90 40.73 ± 4.49 16.79 ± 3.74 - Main ERCP finding 0.164 Ingrowth (65) 91.99 ± 2.72 89.79 ± 3.07 71.64 ± 4.86 40.76 ± 5.62 20.97 ± 5.05 Gallstone(s)/debris (14) 90.91 ± 6.13 90.91 ± 6.13 78.67 ± 9.67 65.56 ± 11.69 21.85 ± 11.01 Stent migration (3) 83.33 ± 15.21 83.33 ± 15.21 62.50 ± 21.35 62.50 ± 21.35 - No obstructive factors (9) 88.24 ± 7.81 81.45 ± 9.72 43.44 ± 15.04 - - SEMS not found ‡ (8) 91.67 ± 7.98 83.33 ± 10.76 64.81 ± 14.26 16.20 ± 14.48 - Overgrowth (3) 100.00 (-) 100.00 (-) 100.00 (-) 66.67 ± 27.22 - Type of stent (general) 0.002 PS (40) 90.71 ± 3.34 87.88 ± 3.79 64.97 ± 5.98 33.14 ± 6.35 7.29 ± 3.96 SEMS (30) 97.44 ± 2.53 94.73 ± 3.63 80.28 ± 6.72 56.59 ± 8.91 39.69 ± 9.46 Type of stent (specific) 0.007 PS (40) 90.71 ± 3.34 87.88 ± 3.79 64.97 ± 5.98 33.14 ± 6.35 7.29 ± 3.96 UCSEMS (10) 100.00 (-) 100.00 (-) 81.25 ± 9.76 60.94 ± 12.52 45.70 ± 13.24 CSEMS (20) 95.45 ± 4.44 90.68 ± 6.28 80.61 ± 8.73 53.74 ± 12.42 33.59 ± 13.85 ERCP, endoscopic retrograde cholangiopancreatography; (-) absence of cases; SEMS, self-expanding metal stent; PS, plastic stent; UCSEMS, uncovered SEMS; CSEMS, covered SEMS. *Estimated probability of survival ± standard error. † Log-rank (Mantel–Cox) test. ‡ Due to duodenal stenosis. In the multivariate analysis, stent repositioning ( P < 0.001) was predictive of RBO and overgrowth was a protective factor against RBO (p = 0.001) (Table 5 ). The risk of RBO did not differ among the various endoscopic reinterventions, including insertion of a PS, CSEMS, UCSEMS, stent cleaning, stent repositioning, and PS removal ( P = 0.264 ǂ ). The RBO risk was 35% lower in patients with overgrowth than in those with ingrowth (SHR: 0.65; 95% CI: 0.52–0.82; P < 0.001). The RBO risk was found to increase in parallel with an increase in the number of reinterventions, ranging from 1.66 times higher (for two reinterventions) to 3.04 times higher (for six reinterventions). In the final model, the proportional-hazards assumption, tested by using the Schoenfeld residuals, was not violated ( P = 0.178). Table 5 Results of the initial and final multivariate Cox models for competing risks of recurrent biliary obstruction Variable Competing-risks model Initial* Final † SHR (95% CI) P SRH (95% CI) P Age (years) 1.00 (1.00–1.01) 0.257 - - ECOG performance status (0 - reference) 0.337 - 1 0.62 (0.37–1.05) 0.073 - - 2 0.61 (0.35–1.06) 0.079 - - 3 0.55 (0.31–0.96) 0.037 - - 4 0.60 (0.33–1.12) 0.110 - - Treatment prior to ERCP (ChT only - reference) 0.876 - - None 0.94 (0.73–1.20) 0.617 - - ChT and RT 0.99 (0.75–1.31) 0.935 - - Endoscopic reintervention (PS insertion - reference) < 0.001 < 0.001 None 1.41 (0.76–2.60) 0.271 0.95 (0.68–1.32) 0.753 UCSEMS insertion 0.68 (0.38–1.22) 0.197 0.74 (0.53–1.05) 0.092 CSEMS insertion 1.20 (0.65–2.23) 0.566 1.15 (0.91–1.45) 0.255 Stent cleaning 1.19 (0.68–2.08) 0.548 1.18 (0.82–1.68) 0.377 Stent repositioning 7.56 (3.79–15.06) < 0.001 6.51 (4.60–9.21) < 0.001 PS removal 1.19 (0.57–2.50) 0.647 1.45 (0.78–2.73) 0.243 Main ERCP finding 0.005 0.001 Ingrowth (reference) Gallstone(s)/debris 0.83 (0.53–1.30) 0.422 0.82 (0.50–1.33) 0.411 Stent migration 0.75 (0.47–1.19) 0.217 0.83 (0.67–1.03) 0.090 No obstructive factors 1.02 (0.55–1.89) 0.945 0.80 (0.49–1.32) 0.382 SEMS not found ‡ 1.46 (0.74–2.86) 0.276 1.03 (0.56–1.87) 0.935 Overgrowth 0.41 (0.24–0.71) 0.002 0.65 (0.52–0.82) < 0.001 Number of reinterventions (1 -reference) < 0.001 < 0.001 2 1.50 (1.06–2.11) 0.021 1.66 (1.27–2.16) < 0.001 3 2.02 (1.14–3.55) 0.015 1.90 (1.23–2.92) 0.004 4 2.34 (1.80–3.04) 0.000 1.97 (1.58–2.47) < 0.001 5 1.82 (0.93–3.54) 0.079 2.82 (2.17–3.66) < 0.001 6 3.71 (1.95–7.06) 0.000 3.04 (2.12–4.36) < 0.001 SHR, subhazard ratio; ECOG, Eastern Cooperative Oncology Group; ERCP, endoscopic retrograde cholangiopancreatography; ChT, chemotherapy; RT, radiotherapy; SEMS, self-expanding metal stent; PS, plastic stent; UCSEMS, uncovered SEMS; CSEMS, covered SEMS. * N = 67 patients (158 reinterventions) † N = 69 patients (165 reinterventions). ‡ Due to duodenal stenosis. Adverse Events non-RBO Adverse events occurred in 7.8% of the endoscopic reinterventions: pancreatitis in four patients, duodenal perforation in one, hepatogastric fistula in one, esophageal varix rupture in one and reintubation post-procedure in one patient. Discussion The endoscopic management of patients with malignant biliary obstruction and an obstructed SEMS is not well stablished. In our sample, the main cause of SEMS obstruction was ingrowth, as well as in most previous retrospective studies ( 18 , 20 – 23 , 25 ). For most of our patients, SEMS dysfunction was treated by inserting a PS or by inserting a second SEMS, which are the two main reinterventions recommended in the literature ( 1 , 14 , 19 – 22 ). In our study we found a clinical success rate of 79.3% for SEMS, 74.4% for PS and stent cleaning resulted in clinical success of 69.6%, with no difference between them. In other studies evaluating insertion of a new stent or stent cleaning ( 1 , 14 , 19 – 22 ), the reported rates of clinical success ranged from 33–82%, although stent patency time was shorter and the number of reinterventions was higher with stent cleaning. In fact, three studies compared stent cleaning alone with the insertion of a PS or SEMS and showed that the former was less effective ( 19 , 21 , 22 ). The fact that we found no difference in clinical success rates among SEMS insertion, PS insertion, and stent cleaning suggests that clinical success is associated with correct diagnosis of the cause of the obstruction. Most previous studies of this topic have evaluated the difference between PSs and SEMSs (CSEMSs or UCSEMSs). Tham et al . ( 20 ) reported 98% of clinical success on endoscopic management of stent occlusion, with no difference among SEMS insertion, PS insertion, and stent cleaning. The authors also found that a PS insertion was more cost-effective. Bueno et al. ( 21 ) reported that clinical success was achieved in 93% of patients undergoing insertion of a PS and in all 4 patients treated with a second SEMS but only in one of 6 patients treated with SEMS cleaning. The lower clinical success observed in our study can partially be attributed by the fact that in 8.5% of our cases no obstruction was detected that would justify the clinical picture and therefore no endoscopic reintervention was implemented. Among those cases, cholestasis persisted in 66.7% and the chance of success was lower than in cases in which there was a reintervention due to the finding of an obstructed metal stent. It is possible that the cholestasis, jaundice, and dilation of the bile duct seen in those cases had non-obstructive causes, such as liver dysfunction resulting from chemotherapy or progression of the malignancy. These results suggest that the absence of an obstructive factor (and consequently no reintervention) is an independent predictor of clinical failure and increases the risk of death. Time to RBO was another predictor of clinical success which demonstrated that the longer the interval between reinterventions, the greater the probability of achieving a favorable clinical outcome. However, the number of reinterventions did not correlated with clinical success, which means that the chances of achieving clinical success did not decrease if it was the first, second or subsequent reintervention. In the present study, patency time was longer after insertion of another SEMS than after insertion of a PS (p = 0.002). Various other studies have shown that SEMSs remain patent for longer. 1,18,22,23,25 Ghazi et al. ( 28 ) showed that although re-occlusion rates are higher for PSs than for SEMSs (46.7% vs 19.7%), the clinical success, mortality, and survival rates were similar between them. However, other studies found no differences between the stent types ( 18 – 21 ). In one systematic review ( 29 ), no difference in patency time was found between PSs and SEMSs. Those differences of the results in the literature are probably related to the patient survival, e.g., in a cohort of patients with more advanced disease, the clinical advantage of the longer patency of SEMS may not be detected. Togawa et al . ( 23 ). compared CSEMSs and UCSEMSs and found that the former presented better patency time. Cho et al. ( 18 ) evaluated the results obtained with different combinations of the first and second SEMS used. The authors found that the use of a CSEMS as the first or second stent provides longer patency than does the use of UCSEMSs as the first and second stents ( 18 ). However, one randomized study also compared the use of CSEMSs and UCSEMSs in patients with RBO and showed no difference in relation to patency time, time to occlusion, survival, and complications ( 3 ). In our study we found no difference between CSEMSs and UCSEMSs ( P = 0.546) and both were superior to PS (p = 0.007). We found that patient age, ECOG performance status, and previous chemotherapy or radiotherapy had no influence on time to RBO of the reintervention. Although statistical analysis indicated that stent repositioning was a predictor of recurrent biliary obstruction, the data was based on a single case, limiting the ability to confirm this hypothesis. In our sample, although the number of previous reinterventions did not impact the chances of clinical success the risk of stent obstruction was found to increase with the number of reinterventions performed. That was probably due to longer survival of these patients. The heterogeneity of our sample in terms of the primary neoplastic disease precluded any assessment of whether the underlying disease influenced the primary or secondary outcome measure. In the present study, 87% of the patients had previously undergone chemotherapy, radiotherapy, or both, none of which were found to have an impact on the clinical success, time to RBO or survival. A retrospective study involving 279 patients with a partially covered SEMS who developed RBO, showed that antineoplastic therapy was a risk factor for RBO in cases of distal malignant biliary obstruction ( 30 ). The hypothesis is that cancer treatment prolongs survival, thus increasing the chance of SEMS obstruction. However, in that study, the time to RBO did not differ between the patients treated with antineoplastic therapy and those receiving clinical support only. Two studies compared the treatment of recurrent hilar versus distal bile duct obstruction ( 21 , 25 ). Both showed that malignant strictures more proximal to the hepatic hilum result in shorter patency time for a second stent. In our study, we found an OR of 0.32 (0.09–1.18) for clinical success for hilar obstruction, not reaching statistical significance (p = 0.086). Maybe this is due to the fact that only 21.4% of our patients had hilar obstruction, resulting in a beta error. Our study has some limitations, including the retrospective, unicentric design and the heterogeneity of the patient sample in relation to the underlying disease. Finally, the fact that the endoscopist decided which approach to take could have introduced a selection bias. In conclusion, in patients with malignant biliary obstruction and an existing, dysfunctional SEMS, reintervention continues to be a challenge and the best approach is still much debated. Our findings indicate that a correct diagnosis is paramount in the management of such cases. Correct identification and treatment of the causal factor typically leads to technical and clinical success. If overgrowth or ingrowth are the cause of SEMS disfunction, the placement of a second SEMS provides longer patency compared to a plastic stent. Furthermore, it is possible that requiring a subsequent reintervention is increased when multiple reinterventions are performed. However, the probability of achieving clinical success in each reintervention remains unchanged. Future studies should also focus on quality of life since none of the endoscopic management options increase patient survival. Patients would probably benefit from procedures that result in a shorter hospital stays and fewer reinterventions. Declarations Author Contribution L.M.A.C.M.; B.C.M. and F..M.F wrote the main manuscript text and prepared figures 1-2. All authors revised the manuscript critically for important intellectual content. References Togawa O, Isayama H, Tsujino T, Nakai Y, Kogure H. Management of dysfunctional covered self-expandable metallic stents in patients with malignant distal biliary obstruction. 2013; Ito K, Ogawa T, Horaguchi J, Koshita S, Fujita N. Reintervention for occluded biliary metal stent for patients with malignant distal biliary stricture. Dig Endosc. 2013;25:126–31. Lee BS, Ryu JK, Jang DK, et al. Reintervention for occluded metal stent in malignant bile duct obstruction: A prospective randomized trial comparing covered and uncovered metal stent. 2016;1901–7. Dumonceau JM, Tringali A, Papanikolaou IS, et al. Endoscopic biliary stenting: Indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline - Updated October 2017. Endoscopy. 2018;50(9):910–30. Nakai Y, Isayama H, Wang H, et al. International consensus statements for endoscopic management of distal biliary stricture. 2020;35:967–79. Irisawa A, Katanuma A, Itoi T. Otaru consensus on biliary stenting for unresectable distal malignant biliary obstruction. 2013;25:52–7. Knyrim, k Wagner, HJ Pausch, J Vakil N. A Prospective, Randomized, Controlled trial of metal stents for malignant obstruction of the comom bile duct. Endoscopy. 1993;25:207–12. Moole H, Jaeger A, Cashman M, et al. Are self-expandable metal stents superior to plastic stents in palliating malignant distal biliary strictures ? A meta-analysis and systematic review. Med J Armed Forces India [Internet]. 2017;73(1):42–8. Available from: http://dx.doi.org/10.1016/j.mjafi.2016.08.014 Zorrón Pu L, De Moura EGH, Bernardo WM, et al. Endoscopic stenting for inoperable malignant biliary obstruction: A systematic review and meta-analysis. World J Gastroenterol. 2015;21(47):13374–85. Sawas T, Al Halabi S, Parsi MA, Vargo JJ. Self-expandable metal stents versus plastic stents for malignant biliary obstruction: A meta-analysis. Gastrointest Endosc [Internet]. 2015;82(2):256–267.e7. Available from: http://dx.doi.org/10.1016/j.gie.2015.03.1980 Tamura T, Itonaga M, Ashida R, et al. Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study. Dig Endosc. 2021;33(7):1170–8. Almadi MA, Barkun A, Martel M. Plastic vs. Self-Expandable Metal Stents for Palliation in Malignant Biliary Obstruction: A Series of Meta-Analyses. Am J Gastroenterol [Internet]. 2017;112(2):260–73. Available from: http://dx.doi.org/10.1038/ajg.2016.512 Halfdanarson TR, Haraldsdottir S, Borad MJ. Advances in systemic therapy for advanced pancreatobiliary malignancies. F1000Research. 2013;2:105. Nennstiel S, Tschurtschenthaler I, Neu B, et al. Management of occluded self-expanding biliary metal stents in malignant biliary disease. Hepatobiliary Pancreat Dis Int. 2018;17:49–54. Ridtitid W. Management of an occluded biliary metallic stent. World J Gastrointest Endosc. 2012;4(5):157. Kim HS, Lee DK, Kim HG, et al. Features of malignant biliary obstruction affecting the patency of metallic stents: a multicenter study. Gastrointest Endosc. 2002;55:359–65. Kadayifci A, Atar M, Forcione DG, et al. Radiofrequency ablation for the management of occluded biliary metal stents. Endoscopy. 2016;Dec 48:1096–101. Cho JH, Jeon TJ, Park JY, et al. Comparison of outcomes among secondary covered metallic, uncovered metallic, and plastic biliary stents in treating occluded primary metallic stents in malignant distal biliary obstruction. Surg Endosc. 2011;25(2):475–82. Katsinelos P, Beltsis A, Chatzimavroudis G, et al. Endoscopic management of occluded biliary uncovered metal stents: A multicenter experience. World J Gastroenterol. 2011;17(1):98–104. Tham TCK, Vandervoort J, Wong RCK, Lichtenstein DR, Vannerman W, Libby ED. Management of occluded biliary Wallstents. Gut. 1998;42:703–7. Bueno JT, Gerdes H, Kurtz RC. Endoscopic management of occluded biliary Wallstents: a cancer center experience. Gastrointest Endosc. 2003;58:879–84. Rogart JN, Boghos A, Rossi F, Al-hashem H, Siddiqui UD. Analysis of endoscopic management of occluded metal biliary stents at a single tertiary care center. Gastrointest Endosc. 2008;68(4):676–82. Togawa O, Kawabe T, Isayama H, Nakai Y. Management of Occluded Uncovered Metallic Stents in Patients With Malignant Distal Biliary Obstructions Using Covered Metallic Stents. J Clin Gastroenterol. 2008;42(5):546–9. Yoon WJ, Ryu JK, Lee JW, et al. Endoscopic management of occluded metal biliary stents: Metal versus 10F plastic stents. World J Gastroenterol. 2010;16(42):5347–52. Ridtitid W, Rerknimitr R. Outcome of second interventions for occluded metallic stents in patients with malignant biliary obstruction. Surg Endosc. 2010;24:2216–20. Isayama H, Hamada T, Fujisawa T, et al. TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage. Dig Endosc. 2024;(March):1–16. Kiriyama S, Kozaka K, Takada T, et al. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci. 2018;25:17–30. Ghazi R, AbiMansour JP, Mahmoud T, et al. Uncovered Versus Fully-Covered Self-Expandable Metal Stents for the Management of Distal Malignant Biliary Obstruction. Gastrointest Endosc. 2023; Shah T, Desai S, Haque M, Dakik H, Fisher D. Management of occluded metal stents in malignant biliary obstruction: similar outcomes with second metal stents compared to plastic stents. Dig Dis Sci. 2012;57(11):2765–73. Nakai Y, Isayama H, Mukai T, Itoi T, Maetani I, Kawakami H. Impact of anticancer treatment on recurrent obstruction in covered metallic stents for malignant biliary obstruction. J Gastroenterol. 2013;48:1293–9. Additional Declarations No competing interests reported. Supplementary Files MachadoetalSupportingInformation.docx Cite Share Download PDF Status: Published Journal Publication published 30 Jan, 2025 Read the published version in Digestive Diseases and Sciences → Version 1 posted Editorial decision: Revision requested 23 Sep, 2024 Reviews received at journal 23 Sep, 2024 Reviewers agreed at journal 11 Sep, 2024 Reviews received at journal 07 Sep, 2024 Reviewers agreed at journal 29 Aug, 2024 Reviewers invited by journal 27 Aug, 2024 Editor assigned by journal 27 Aug, 2024 Submission checks completed at journal 22 Aug, 2024 First submitted to journal 21 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4951976","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":355491896,"identity":"76b5e63e-c7c0-46bf-94d8-cf8eefd24277","order_by":0,"name":"Lara Meireles Azeredo Coutinho Machado","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApUlEQVRIiWNgGAWjYBACPigtByKYidLCBqWNSdeS2EC8FvazDz/dqLFL33D+7AHmwj3EaOFJN5bOOZacu+FGXgLzjGdEOSyNQTqH7QBQC48BM88BYrTwP2P+nfPvQLrB+TPEapFIY5PObTuQYHAgh2gtz9isc/uSDWcC/XJ4BjFa+PnTmG/nfLOT5zt/9uDjAmK0IAEeBhI1gLSMglEwCkbBKMAKAGUMMZ2HM/kdAAAAAElFTkSuQmCC","orcid":"","institution":"Instituto do Câncer do Estado de São Paulo","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Lara","middleName":"Meireles Azeredo Coutinho","lastName":"Machado","suffix":""},{"id":355491898,"identity":"cfbfb22f-f2e9-408e-89d4-7da2a621d18a","order_by":1,"name":"Bruno Costa Martins","email":"","orcid":"","institution":"Instituto do Câncer do Estado de São Paulo","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bruno","middleName":"Costa","lastName":"Martins","suffix":""},{"id":355491901,"identity":"033fd970-0464-4074-9f3f-08e7d1a5a00c","order_by":2,"name":"Marcelo Simas Lima","email":"","orcid":"","institution":"Instituto do Câncer do Estado de São Paulo","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Marcelo","middleName":"Simas","lastName":"Lima","suffix":""},{"id":355491903,"identity":"7420d56b-6090-40ac-8044-da0d3334f72e","order_by":3,"name":"Sebastian Geiger","email":"","orcid":"","institution":"Instituto do Câncer do Estado de São Paulo","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sebastian","middleName":"","lastName":"Geiger","suffix":""},{"id":355491904,"identity":"cd6cb887-970c-4faf-95bc-41d9efff8d73","order_by":4,"name":"Luciano Lenz","email":"","orcid":"","institution":"Instituto do Câncer do Estado de São Paulo","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Luciano","middleName":"","lastName":"Lenz","suffix":""},{"id":355491905,"identity":"13394809-acce-43db-939f-fc3cff44f987","order_by":5,"name":"Gustavo Andrade Paulo","email":"","orcid":"","institution":"Instituto do Câncer do Estado de São Paulo","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gustavo","middleName":"Andrade","lastName":"Paulo","suffix":""},{"id":355491906,"identity":"0ef3fd76-7423-41e3-8450-022fb0a3c0ea","order_by":6,"name":"Adriana Safatle-Ribeiro","email":"","orcid":"","institution":"Instituto do Câncer do Estado de São Paulo","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Adriana","middleName":"","lastName":"Safatle-Ribeiro","suffix":""},{"id":355491907,"identity":"ee186551-daf4-4bd1-8485-5829bbf6055c","order_by":7,"name":"Ulysses Ribeiro Jr","email":"","orcid":"","institution":"Instituto do Câncer do Estado de São Paulo","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ulysses","middleName":"","lastName":"Ribeiro","suffix":"Jr"},{"id":355491908,"identity":"f8872b46-443c-4a09-b0b2-5a0715016a0f","order_by":8,"name":"Fauze Maluf-Filho","email":"","orcid":"","institution":"Instituto do Câncer do Estado de São Paulo","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fauze","middleName":"","lastName":"Maluf-Filho","suffix":""}],"badges":[],"createdAt":"2024-08-21 13:34:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4951976/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4951976/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10620-025-08853-y","type":"published","date":"2025-01-30T15:58:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66747305,"identity":"3e5fa597-c676-4efe-8e13-e44fe6104a5c","added_by":"auto","created_at":"2024-10-16 06:47:22","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":219776,"visible":true,"origin":"","legend":"\u003cp\u003eSample selection process\u003c/p\u003e\n\u003cp\u003e*SEMS (self-expanding metal stent)\u003c/p\u003e\n\u003cp\u003e** ERCP (endoscopic retrograde cholangiopancreatography)\u003c/p\u003e\n\u003cp\u003e*** RBO (recurrent biliary obstruction) retrograde cholangiopancreatography\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4951976/v1/18c360537881db9cf4fa75fb.jpeg"},{"id":66747306,"identity":"3a7db151-3b6c-4807-ab04-f01a29deacc7","added_by":"auto","created_at":"2024-10-16 06:47:22","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":157819,"visible":true,"origin":"","legend":"\u003cp\u003ePatency time of PS, uncovered SEMSs (UCSEMSs), and covered SEMSs (CSEMSs)\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4951976/v1/81cfbc41baaf3daf5d066b24.jpeg"},{"id":75351482,"identity":"81f2bf85-2f3a-4d9a-b268-728b26555424","added_by":"auto","created_at":"2025-02-03 16:11:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1379435,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4951976/v1/dcaf4e11-579d-46d6-886a-1f817fd217d8.pdf"},{"id":66747307,"identity":"380ce3dd-feeb-4416-a5f3-47f167b2e180","added_by":"auto","created_at":"2024-10-16 06:47:22","extension":"docx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":28014,"visible":true,"origin":"","legend":"","description":"","filename":"MachadoetalSupportingInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-4951976/v1/fe1be8c8639321914195c574.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Results of endoscopic treatment of recurrent malignant biliary obstruction in patients with self-expanding metal stents","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndoscopic biliary drainage with self-expanding metal stent (SEMS) placement is the palliative strategy of choice in patients with malignant biliary obstruction due to unresectable neoplasia (\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Several randomized studies and meta-analyses showed that a SEMS is superior to a plastic stent (PS) in terms of patency and survival time, reducing the risk of cholangitis and endoscopic reintervention (\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRecent advances in the treatment of unresectable malignant pancreatobiliary diseases have increased patient survival, thus increasing the prevalence of recurrent biliary obstruction (RBO) in patients with a SEMS (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Studies indicate that SEMS dysfunction occurs in 5\u0026ndash;40% of such patients (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe causes of RBO include tumor ingrowth (overgrowth), sludge formation, food impaction, primary gallstones and stent migration among others. In cases of RBO after SEMS, the best endoscopic strategy is unclear. The SEMS can be cleaned mechanically with a balloon catheter, a PS or a new SEMS can be inserted within the previous stent. Other less common approaches include replacing the SEMS and radiofrequency ablation (RFA) (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Only a few studies have compared the various approaches of RBO (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22 CR23\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough some strategies have been devised, there is no consensus regarding the best management of an occluded SEMS. The European Society of Gastrointestinal Endoscopy recommends that SEMS dysfunction should be managed by placing a new PS or SEMS, without making a distinction between the two (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In a consensus statement, experts in interventional endoscopy in Asia proposed that the therapeutic approach to patients with RBO should be customized depending on the etiology and severity of the obstruction (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In another consensus statement regarding RBO, from Japan, stent cleaning was described as ineffective and the insertion of a second SEMS would lead to greater patency in comparison with the insertion of a PS (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Therefore, given the lack of a consensus in the literature regarding the approach to RBO, the management of SEMS dysfunction merits investigation.\u003c/p\u003e \u003cp\u003eThe present study aimed to compare the results of different endoscopic approaches in patients with SEMS and RBO. The primary outcomes were clinical success and time to a new biliary obstruction.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003eThis was an observational study including all patients with a SEMS for the treatment of malignant strictures, who underwent reintervention with endoscopic retrograde cholangiopancreatography (ERCP) to investigate RBO between January 2011 and December 2018 at the \u003cem\u003eCancer Institute of the University of S\u0026atilde;o Paulo (ICESP), S\u0026atilde;o Paulo, Brazil\u003c/em\u003e. This study was approved by our institution Research Ethics Committee (Reference no. 4.995.272).\u003c/p\u003e \u003cp\u003eInclusion criteria were patients with a SEMS placed because of malignant biliary strictures who underwent ERCP to investigate and treat recurrent biliary obstruction. Exclusion criteria were patients lost to follow-up after the insertion of the first SEMS.\u003c/p\u003e \u003cp\u003eThe sample selection process is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eThe indications for reintervention with ERCP were recorded and categorized as: recurrence of cholestasis; cholangitis; dilation of the biliary tree; or other. All procedures were performed in the Endoscopy Unit of our institution. During ERCP, the cause of the obstruction was identified and noted as follows: ingrowth; overgrowth; biliary sludge/gallstones or stent migration. The endoscopist intervened based on the cause of obstruction identified during ERCP. The expected procedures for treating RBO were the insertion of a PS or a second SEMS within the primary stent; mechanical cleaning of the SEMS with a balloon catheter and/or Dormia basket. In each reintervention, the choice between a PS and a SEMS was left at the discretion of the endoscopist.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDefinitions\u003c/h2\u003e \u003cp\u003eThe definitions adopted in this study were based on the Tokyo criteria, updated in 2024 (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Clinical success was defined as a reduction of at least 50% or normalization in the bilirubin level within the first 14 days after stent placement. Time to RBO was defined as the time between endoscopic reintervention and the new obstruction. Occlusion of a SEMS or PS was defined by biochemical evidence of cholestasis, accompanied by biliary dilation on imaging studies, together with endoscopic findings consistent with occlusion. Ingrowth was diagnosed when cholangiography demonstrated a persistent biliary stricture within a covered or uncovered SEMS (CSEMS or UCSEMS, respectively) after the bile duct had been cleaned. Similarly, overgrowth was diagnosed when there was persistent stenosis at the proximal or distal ends of the SEMS. Stent migration was defined as RBO caused by complete or partial (proximal or distal) stent migration. Technical success was defined as resolution of the cause of the obstruction with free flow of contrast under cholangiography.\u003c/p\u003e \u003cp\u003eCholangitis were defined according to the 2018 Tokyo Guidelines (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), as signs of systemic inflammation, cholestasis, or imaging examinations showing bile duct obstruction. Adverse events were defined according to the 2024 Tokyo criteria (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), as RBO, pancreatitis, cholangitis, cholecystitis, bleeding, perforation or any other complication related to the placement of the stent in the bile duct.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were expressed as absolute and relative frequencies, whereas numerical variables were expressed as descriptive statistics (mean, standard deviation, range, median, and quartiles). For comparisons between categorical variables, we used the chi-square test (or Fisher\u0026rsquo;s exact test in the case of small samples). For comparisons of means, we used Student\u0026rsquo;s t-test for independent samples.\u003c/p\u003e \u003cp\u003eWe used generalized estimating equations (GEEs) to evaluate the simultaneous effects that demographic and clinical characteristics had on clinical success. We used Kaplan\u0026ndash;Meier curves to analyze survival to endoscopic reintervention or death. Survival functions were compared by the log-rank (Mantel\u0026ndash;Cox) test. Because more than one approach could be taken in each patient, frailty models were used. For the time to RBO, the Cox competing-risks model (Fine\u0026ndash;Gray model) was used (the survival function was expressed as the subhazard ratio - SHR).\u003c/p\u003e \u003cp\u003eVariables significant at 20% in the univariate analysis were selected for inclusion in the initial multivariate models. Variables that were not significant at 5% were then eliminated one by one in order of significance (backward elimination).\u003c/p\u003e \u003cp\u003eIn our exploratory analyses, reinterventions were evaluated as independent events.\u003c/p\u003e \u003cp\u003eFor all statistical tests, we adopted a significance level of 5%. Statistical analyses were performed with the IBM SPSS Statistics software package, version 20.0 (IBM Corp., Armonk, NY, USA) and Stata software, version 12.0 (Stata Corp LP, College Station, TX, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eBetween January 2011 and December 2018, 312 patients underwent endoscopic SEMS insertion for the treatment of biliary obstruction at our institution. Of those, 71 (22.7%) developed RBO and required endoscopic reintervention. One patient was lost to follow up and was excluded of the analysis. The mean age was 61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3 years, and 37 patients (52.9%) were men. The majority of patients had a good performance status (ECOG 0\u0026ndash;2 in 70% of the patients), had previously undergone chemotherapy (89.7%) and had distal biliary obstruction (78.6%). Demographic and clinical characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics of the patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (47.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (52.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge* (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.0 (28.0\u0026ndash;88.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG performance status, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (15.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (34.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (22.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment prior to ERCP, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (10.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (77.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy and radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (11.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo information available\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObstruction topography, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHilar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (21.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (78.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eSD, standard deviation; ECOG, Eastern Cooperative Oncology Group; ERCP, endoscopic retrograde cholangiopancreatography.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e*At ERCP.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe main cause of RBO was ingrowth occurring in 65 procedures (63.7%), followed by sludge/gallstones in 14 procedures (13.7%). The reintervention involved PS insertion in 38.4%, SEMS insertion in 30 (28.8%) and stent cleaning in 23 (22%). In 9 cases, no obstructive factor was seen and thus no endoscopic reintervention was performed. In one case, the stent was only repositioned; in another, the existing SEMS was removed, and no further action was taken (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the endoscopic reinterventions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;105)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMain ERCP finding (cause of RBO), \u003cem\u003en\u003c/em\u003e (%)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIngrowth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (63.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGallstone(s)/debris\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (13.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProximal migration of the SEMS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsence of obstructive factors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (8.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSEMS not found\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (7.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOvergrowth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEndoscopic reintervention, \u003cem\u003en\u003c/em\u003e (%)\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePS insertion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (38.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSEMS insertion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (28.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStent cleaning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (22.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (8.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStent repositioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePS removal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNumber of reintervention, \u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e1st\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (71,4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e2nd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (15,7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e3rd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (8,6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4th\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eERCP, endoscopic retrograde cholangiopancreatography; RBO, recurrent biliary obstruction; SEMS, self-expanding metal stent; PS, plastic stent.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e*Data available for only 102 procedures.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eDue to duodenal stenosis.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003eData available for only 104 procedures.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFifty patients underwent only one reintervention and 20 required more than one resulting in a total of 105 ERCP sessions for maintaining stent patency\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eTechnical success and Clinical success\u003c/h2\u003e \u003cp\u003eTechnical success was achieved in 91.4% of the 105 interventions. Causes of technical failure occurred in five patients with duodenal obstruction, which prevented endoscopic access to the bile duct.\u003c/p\u003e \u003cp\u003eClinical success was achieved in 71.8% of the 105 interventions. As shown in Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e, clinical success was not associated with the endoscopic approach, ECOG performance status or prior chemotherapy/radiotherapy. Of nine ERCPs in which no action was taken (because the stent was found to be well positioned and unobstructed), 67% had clinical failure and the risk of death was approximately 4 times higher in these patients (HR: 3.94; 95% CI: 1.57\u0026ndash;9.92; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004).\u003c/p\u003e \u003cp\u003eIn the multivariate analysis (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), younger age (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006), no reintervention (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024), and shorter time to RBO (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008) were predictors of the clinical failure. The chance of clinical success was 83% (1-0.17) lower in patients who underwent no reintervention than in patients who underwent any reintervention (OR\u0026thinsp;=\u0026thinsp;0.17; p\u0026thinsp;=\u0026thinsp;0.024). When the time to RBO between reinterventions was longer, the odds of clinical success of that intervention was higher (OR: 1.007; 95% CI: 1.002\u0026ndash;1.013; p\u0026thinsp;=\u0026thinsp;0.008). However, the number of reinterventions did not impact on the odds of clinical success.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of final logistic regression model for the predictors of clinical success\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eInitial model*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eFinal model\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.05 (1.01\u0026ndash;1.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.11 (1.03\u0026ndash;1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObstruction topography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHilar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.32 (0.09\u0026ndash;1.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDistal (reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndoscopic reintervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.10 (0.02\u0026ndash;0.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17 (0.04\u0026ndash;0.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSEMS insertion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.14 (0.32\u0026ndash;3.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.841\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.27 (0.41\u0026ndash;3.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.677\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStent cleaning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.45 (0.10\u0026ndash;2.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.65 (0.19\u0026ndash;2.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.499\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther reinterventions\u003csup\u003e\u0026Dagger;\u003c/sup\u003e (reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of reinterventions (1 - reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.93 (0.30\u0026ndash;2.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.900\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.81 (0.15\u0026ndash;4.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.810\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.15 (0.36\u0026ndash;3.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.811\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.65 (0.23\u0026ndash;1.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.412\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(1)\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.90 (0.14\u0026ndash;5.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.911\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to RBO (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.007 (1.001\u0026ndash;1.013)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.007 (1.002\u0026ndash;1.013)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eSEMS, self-expanding metal stent; RBO, recurrent biliary obstruction\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;96 reinterventions in 59 patients.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;102 reinterventions in 70 patients.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003ePS insertion, PS removal, and stent repositioning.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003eAbsence of clinical failure.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eRecurrent biliary obstruction\u003c/h2\u003e \u003cp\u003eThe mean and median stent patency after endoscopic reintervention were 252.8 days (95% CI: 186.8\u0026ndash;318.9) and 122.0 days (95% CI: 87.6\u0026ndash;156.4), respectively. Time to RBO was longer in patients treated with SEMS compared with PS (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002, Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). UCSEMSs were comparable to CSEMSs (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.546) and both were superior to PS (Table S2). Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the cumulative patency by stent type.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of the post-reintervention patency analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eCumulative time to RBO (%)*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 days\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 month\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 year\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal (n of interventions)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.60\u0026thinsp;\u0026plusmn;\u0026thinsp;2.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88.29\u0026thinsp;\u0026plusmn;\u0026thinsp;2.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69.44\u0026thinsp;\u0026plusmn;\u0026thinsp;3.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.73\u0026thinsp;\u0026plusmn;\u0026thinsp;4.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.79\u0026thinsp;\u0026plusmn;\u0026thinsp;3.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMain ERCP finding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.164\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIngrowth (65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.99\u0026thinsp;\u0026plusmn;\u0026thinsp;2.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.79\u0026thinsp;\u0026plusmn;\u0026thinsp;3.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71.64\u0026thinsp;\u0026plusmn;\u0026thinsp;4.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.76\u0026thinsp;\u0026plusmn;\u0026thinsp;5.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.97\u0026thinsp;\u0026plusmn;\u0026thinsp;5.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGallstone(s)/debris (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.91\u0026thinsp;\u0026plusmn;\u0026thinsp;6.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90.91\u0026thinsp;\u0026plusmn;\u0026thinsp;6.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.67\u0026thinsp;\u0026plusmn;\u0026thinsp;9.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.56\u0026thinsp;\u0026plusmn;\u0026thinsp;11.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.85\u0026thinsp;\u0026plusmn;\u0026thinsp;11.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStent migration (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83.33\u0026thinsp;\u0026plusmn;\u0026thinsp;15.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.33\u0026thinsp;\u0026plusmn;\u0026thinsp;15.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62.50\u0026thinsp;\u0026plusmn;\u0026thinsp;21.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.50\u0026thinsp;\u0026plusmn;\u0026thinsp;21.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo obstructive factors (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88.24\u0026thinsp;\u0026plusmn;\u0026thinsp;7.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.45\u0026thinsp;\u0026plusmn;\u0026thinsp;9.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43.44\u0026thinsp;\u0026plusmn;\u0026thinsp;15.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSEMS not found\u003csup\u003e\u0026Dagger;\u003c/sup\u003e (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.67\u0026thinsp;\u0026plusmn;\u0026thinsp;7.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.33\u0026thinsp;\u0026plusmn;\u0026thinsp;10.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.81\u0026thinsp;\u0026plusmn;\u0026thinsp;14.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.20\u0026thinsp;\u0026plusmn;\u0026thinsp;14.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOvergrowth (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100.00 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100.00 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100.00 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e66.67\u0026thinsp;\u0026plusmn;\u0026thinsp;27.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of stent (general)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePS (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.71\u0026thinsp;\u0026plusmn;\u0026thinsp;3.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.88\u0026thinsp;\u0026plusmn;\u0026thinsp;3.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.97\u0026thinsp;\u0026plusmn;\u0026thinsp;5.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33.14\u0026thinsp;\u0026plusmn;\u0026thinsp;6.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.29\u0026thinsp;\u0026plusmn;\u0026thinsp;3.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSEMS (30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.44\u0026thinsp;\u0026plusmn;\u0026thinsp;2.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94.73\u0026thinsp;\u0026plusmn;\u0026thinsp;3.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80.28\u0026thinsp;\u0026plusmn;\u0026thinsp;6.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56.59\u0026thinsp;\u0026plusmn;\u0026thinsp;8.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e39.69\u0026thinsp;\u0026plusmn;\u0026thinsp;9.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of stent (specific)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePS (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.71\u0026thinsp;\u0026plusmn;\u0026thinsp;3.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.88\u0026thinsp;\u0026plusmn;\u0026thinsp;3.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.97\u0026thinsp;\u0026plusmn;\u0026thinsp;5.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33.14\u0026thinsp;\u0026plusmn;\u0026thinsp;6.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.29\u0026thinsp;\u0026plusmn;\u0026thinsp;3.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUCSEMS (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100.00 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100.00 (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81.25\u0026thinsp;\u0026plusmn;\u0026thinsp;9.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60.94\u0026thinsp;\u0026plusmn;\u0026thinsp;12.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45.70\u0026thinsp;\u0026plusmn;\u0026thinsp;13.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSEMS (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95.45\u0026thinsp;\u0026plusmn;\u0026thinsp;4.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90.68\u0026thinsp;\u0026plusmn;\u0026thinsp;6.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80.61\u0026thinsp;\u0026plusmn;\u0026thinsp;8.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53.74\u0026thinsp;\u0026plusmn;\u0026thinsp;12.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33.59\u0026thinsp;\u0026plusmn;\u0026thinsp;13.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eERCP, endoscopic retrograde cholangiopancreatography; (-) absence of cases; SEMS, self-expanding metal stent; PS, plastic stent; UCSEMS, uncovered SEMS; CSEMS, covered SEMS.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e*Estimated probability of survival\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eLog-rank (Mantel\u0026ndash;Cox) test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003eDue to duodenal stenosis.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the multivariate analysis, stent repositioning (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) was predictive of RBO and overgrowth was a protective factor against RBO (p\u0026thinsp;=\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The risk of RBO did not differ among the various endoscopic reinterventions, including insertion of a PS, CSEMS, UCSEMS, stent cleaning, stent repositioning, and PS removal (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.264\u003csup\u003eǂ\u003c/sup\u003e). The RBO risk was 35% lower in patients with overgrowth than in those with ingrowth (SHR: 0.65; 95% CI: 0.52\u0026ndash;0.82; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The RBO risk was found to increase in parallel with an increase in the number of reinterventions, ranging from 1.66 times higher (for two reinterventions) to 3.04 times higher (for six reinterventions). In the final model, the proportional-hazards assumption, tested by using the Schoenfeld residuals, was not violated (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.178).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of the initial and final multivariate Cox models for competing risks of recurrent biliary obstruction\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eCompeting-risks model\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eInitial*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eFinal\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSHR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSRH (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00 (1.00\u0026ndash;1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECOG performance status (0 - reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.337\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.62 (0.37\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.073\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.61 (0.35\u0026ndash;1.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.079\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.55 (0.31\u0026ndash;0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.60 (0.33\u0026ndash;1.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment prior to ERCP (ChT only - reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.876\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.94 (0.73\u0026ndash;1.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.617\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChT and RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.99 (0.75\u0026ndash;1.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.935\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndoscopic reintervention (PS insertion - reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.41 (0.76\u0026ndash;2.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.95 (0.68\u0026ndash;1.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.753\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUCSEMS insertion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.68 (0.38\u0026ndash;1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.197\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.74 (0.53\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSEMS insertion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.20 (0.65\u0026ndash;2.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.566\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.15 (0.91\u0026ndash;1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStent cleaning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.19 (0.68\u0026ndash;2.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.548\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.18 (0.82\u0026ndash;1.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.377\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStent repositioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.56 (3.79\u0026ndash;15.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.51 (4.60\u0026ndash;9.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePS removal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.19 (0.57\u0026ndash;2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.647\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.45 (0.78\u0026ndash;2.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMain ERCP finding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIngrowth (reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGallstone(s)/debris\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.83 (0.53\u0026ndash;1.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.422\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.82 (0.50\u0026ndash;1.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.411\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStent migration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.75 (0.47\u0026ndash;1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.83 (0.67\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.090\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo obstructive factors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.02 (0.55\u0026ndash;1.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.945\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.80 (0.49\u0026ndash;1.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.382\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSEMS not found\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.46 (0.74\u0026ndash;2.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.03 (0.56\u0026ndash;1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.935\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOvergrowth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.41 (0.24\u0026ndash;0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.65 (0.52\u0026ndash;0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of reinterventions (1 -reference)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.50 (1.06\u0026ndash;2.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.66 (1.27\u0026ndash;2.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.02 (1.14\u0026ndash;3.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.90 (1.23\u0026ndash;2.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.34 (1.80\u0026ndash;3.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.97 (1.58\u0026ndash;2.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.82 (0.93\u0026ndash;3.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.079\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.82 (2.17\u0026ndash;3.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.71 (1.95\u0026ndash;7.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.04 (2.12\u0026ndash;4.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eSHR, subhazard ratio; ECOG, Eastern Cooperative Oncology Group; ERCP, endoscopic retrograde cholangiopancreatography; ChT, chemotherapy; RT, radiotherapy; SEMS, self-expanding metal stent; PS, plastic stent; UCSEMS, uncovered SEMS; CSEMS, covered SEMS.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;67 patients (158 reinterventions)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;69 patients (165 reinterventions).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003eDue to duodenal stenosis.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAdverse Events non-RBO\u003c/h2\u003e \u003cp\u003eAdverse events occurred in 7.8% of the endoscopic reinterventions: pancreatitis in four patients, duodenal perforation in one, hepatogastric fistula in one, esophageal varix rupture in one and reintubation post-procedure in one patient.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe endoscopic management of patients with malignant biliary obstruction and an obstructed SEMS is not well stablished.\u003c/p\u003e \u003cp\u003eIn our sample, the main cause of SEMS obstruction was ingrowth, as well as in most previous retrospective studies (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFor most of our patients, SEMS dysfunction was treated by inserting a PS or by inserting a second SEMS, which are the two main reinterventions recommended in the literature (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). In our study we found a clinical success rate of 79.3% for SEMS, 74.4% for PS and stent cleaning resulted in clinical success of 69.6%, with no difference between them. In other studies evaluating insertion of a new stent or stent cleaning (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), the reported rates of clinical success ranged from 33\u0026ndash;82%, although stent patency time was shorter and the number of reinterventions was higher with stent cleaning. In fact, three studies compared stent cleaning alone with the insertion of a PS or SEMS and showed that the former was less effective (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe fact that we found no difference in clinical success rates among SEMS insertion, PS insertion, and stent cleaning suggests that clinical success is associated with correct diagnosis of the cause of the obstruction. Most previous studies of this topic have evaluated the difference between PSs and SEMSs (CSEMSs or UCSEMSs). Tham \u003cem\u003eet al\u003c/em\u003e. (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) reported 98% of clinical success on endoscopic management of stent occlusion, with no difference among SEMS insertion, PS insertion, and stent cleaning. The authors also found that a PS insertion was more cost-effective. Bueno \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) reported that clinical success was achieved in 93% of patients undergoing insertion of a PS and in all 4 patients treated with a second SEMS but only in one of 6 patients treated with SEMS cleaning.\u003c/p\u003e \u003cp\u003eThe lower clinical success observed in our study can partially be attributed by the fact that in 8.5% of our cases no obstruction was detected that would justify the clinical picture and therefore no endoscopic reintervention was implemented. Among those cases, cholestasis persisted in 66.7% and the chance of success was lower than in cases in which there was a reintervention due to the finding of an obstructed metal stent. It is possible that the cholestasis, jaundice, and dilation of the bile duct seen in those cases had non-obstructive causes, such as liver dysfunction resulting from chemotherapy or progression of the malignancy. These results suggest that the absence of an obstructive factor (and consequently no reintervention) is an independent predictor of clinical failure and increases the risk of death. Time to RBO was another predictor of clinical success which demonstrated that the longer the interval between reinterventions, the greater the probability of achieving a favorable clinical outcome. However, the number of reinterventions did not correlated with clinical success, which means that the chances of achieving clinical success did not decrease if it was the first, second or subsequent reintervention.\u003c/p\u003e \u003cp\u003eIn the present study, patency time was longer after insertion of another SEMS than after insertion of a PS (p\u0026thinsp;=\u0026thinsp;0.002). Various other studies have shown that SEMSs remain patent for longer.\u003csup\u003e1,18,22,23,25\u003c/sup\u003e Ghazi \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) showed that although re-occlusion rates are higher for PSs than for SEMSs (46.7% \u003cem\u003evs\u003c/em\u003e 19.7%), the clinical success, mortality, and survival rates were similar between them. However, other studies found no differences between the stent types (\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In one systematic review (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), no difference in patency time was found between PSs and SEMSs. Those differences of the results in the literature are probably related to the patient survival, e.g., in a cohort of patients with more advanced disease, the clinical advantage of the longer patency of SEMS may not be detected.\u003c/p\u003e \u003cp\u003eTogawa \u003cem\u003eet al\u003c/em\u003e. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). compared CSEMSs and UCSEMSs and found that the former presented better patency time. Cho \u003cem\u003eet al.\u003c/em\u003e (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) evaluated the results obtained with different combinations of the first and second SEMS used. The authors found that the use of a CSEMS as the first or second stent provides longer patency than does the use of UCSEMSs as the first and second stents (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). However, one randomized study also compared the use of CSEMSs and UCSEMSs in patients with RBO and showed no difference in relation to patency time, time to occlusion, survival, and complications (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In our study we found no difference between CSEMSs and UCSEMSs (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.546) and both were superior to PS (p\u0026thinsp;=\u0026thinsp;0.007).\u003c/p\u003e \u003cp\u003eWe found that patient age, ECOG performance status, and previous chemotherapy or radiotherapy had no influence on time to RBO of the reintervention. Although statistical analysis indicated that stent repositioning was a predictor of recurrent biliary obstruction, the data was based on a single case, limiting the ability to confirm this hypothesis.\u003c/p\u003e \u003cp\u003eIn our sample, although the number of previous reinterventions did not impact the chances of clinical success the risk of stent obstruction was found to increase with the number of reinterventions performed. That was probably due to longer survival of these patients.\u003c/p\u003e \u003cp\u003eThe heterogeneity of our sample in terms of the primary neoplastic disease precluded any assessment of whether the underlying disease influenced the primary or secondary outcome measure. In the present study, 87% of the patients had previously undergone chemotherapy, radiotherapy, or both, none of which were found to have an impact on the clinical success, time to RBO or survival. A retrospective study involving 279 patients with a partially covered SEMS who developed RBO, showed that antineoplastic therapy was a risk factor for RBO in cases of distal malignant biliary obstruction (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). The hypothesis is that cancer treatment prolongs survival, thus increasing the chance of SEMS obstruction. However, in that study, the time to RBO did not differ between the patients treated with antineoplastic therapy and those receiving clinical support only.\u003c/p\u003e \u003cp\u003eTwo studies compared the treatment of recurrent hilar versus distal bile duct obstruction (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Both showed that malignant strictures more proximal to the hepatic hilum result in shorter patency time for a second stent. In our study, we found an OR of 0.32 (0.09\u0026ndash;1.18) for clinical success for hilar obstruction, not reaching statistical significance (p\u0026thinsp;=\u0026thinsp;0.086). Maybe this is due to the fact that only 21.4% of our patients had hilar obstruction, resulting in a beta error.\u003c/p\u003e \u003cp\u003eOur study has some limitations, including the retrospective, unicentric design and the heterogeneity of the patient sample in relation to the underlying disease. Finally, the fact that the endoscopist decided which approach to take could have introduced a selection bias.\u003c/p\u003e \u003cp\u003eIn conclusion, in patients with malignant biliary obstruction and an existing, dysfunctional SEMS, reintervention continues to be a challenge and the best approach is still much debated. Our findings indicate that a correct diagnosis is paramount in the management of such cases. Correct identification and treatment of the causal factor typically leads to technical and clinical success. If overgrowth or ingrowth are the cause of SEMS disfunction, the placement of a second SEMS provides longer patency compared to a plastic stent. Furthermore, it is possible that requiring a subsequent reintervention is increased when multiple reinterventions are performed. However, the probability of achieving clinical success in each reintervention remains unchanged. Future studies should also focus on quality of life since none of the endoscopic management options increase patient survival. Patients would probably benefit from procedures that result in a shorter hospital stays and fewer reinterventions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eL.M.A.C.M.; B.C.M. and F..M.F wrote the main manuscript text and prepared figures 1-2. All authors revised the manuscript critically for important intellectual content.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTogawa O, Isayama H, Tsujino T, Nakai Y, Kogure H. Management of dysfunctional covered self-expandable metallic stents in patients with malignant distal biliary obstruction. 2013;\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIto K, Ogawa T, Horaguchi J, Koshita S, Fujita N. Reintervention for occluded biliary metal stent for patients with malignant distal biliary stricture. Dig Endosc. 2013;25:126\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee BS, Ryu JK, Jang DK, et al. Reintervention for occluded metal stent in malignant bile duct obstruction: A prospective randomized trial comparing covered and uncovered metal stent. 2016;1901\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDumonceau JM, Tringali A, Papanikolaou IS, et al. Endoscopic biliary stenting: Indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline - Updated October 2017. Endoscopy. 2018;50(9):910\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakai Y, Isayama H, Wang H, et al. International consensus statements for endoscopic management of distal biliary stricture. 2020;35:967\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIrisawa A, Katanuma A, Itoi T. Otaru consensus on biliary stenting for unresectable distal malignant biliary obstruction. 2013;25:52\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKnyrim, k Wagner, HJ Pausch, J Vakil N. A Prospective, Randomized, Controlled trial of metal stents for malignant obstruction of the comom bile duct. Endoscopy. 1993;25:207\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoole H, Jaeger A, Cashman M, et al. Are self-expandable metal stents superior to plastic stents in palliating malignant distal biliary strictures ? A meta-analysis and systematic review. Med J Armed Forces India [Internet]. 2017;73(1):42\u0026ndash;8. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1016/j.mjafi.2016.08.014\u003c/span\u003e\u003cspan address=\"10.1016/j.mjafi.2016.08.014\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZorr\u0026oacute;n Pu L, De Moura EGH, Bernardo WM, et al. Endoscopic stenting for inoperable malignant biliary obstruction: A systematic review and meta-analysis. World J Gastroenterol. 2015;21(47):13374\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSawas T, Al Halabi S, Parsi MA, Vargo JJ. Self-expandable metal stents versus plastic stents for malignant biliary obstruction: A meta-analysis. Gastrointest Endosc [Internet]. 2015;82(2):256\u0026ndash;267.e7. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1016/j.gie.2015.03.1980\u003c/span\u003e\u003cspan address=\"10.1016/j.gie.2015.03.1980\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTamura T, Itonaga M, Ashida R, et al. Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study. Dig Endosc. 2021;33(7):1170\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlmadi MA, Barkun A, Martel M. Plastic vs. Self-Expandable Metal Stents for Palliation in Malignant Biliary Obstruction: A Series of Meta-Analyses. Am J Gastroenterol [Internet]. 2017;112(2):260\u0026ndash;73. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1038/ajg.2016.512\u003c/span\u003e\u003cspan address=\"10.1038/ajg.2016.512\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHalfdanarson TR, Haraldsdottir S, Borad MJ. Advances in systemic therapy for advanced pancreatobiliary malignancies. F1000Research. 2013;2:105.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNennstiel S, Tschurtschenthaler I, Neu B, et al. Management of occluded self-expanding biliary metal stents in malignant biliary disease. Hepatobiliary Pancreat Dis Int. 2018;17:49\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRidtitid W. Management of an occluded biliary metallic stent. World J Gastrointest Endosc. 2012;4(5):157.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim HS, Lee DK, Kim HG, et al. Features of malignant biliary obstruction affecting the patency of metallic stents: a multicenter study. Gastrointest Endosc. 2002;55:359\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKadayifci A, Atar M, Forcione DG, et al. Radiofrequency ablation for the management of occluded biliary metal stents. Endoscopy. 2016;Dec 48:1096\u0026ndash;101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho JH, Jeon TJ, Park JY, et al. Comparison of outcomes among secondary covered metallic, uncovered metallic, and plastic biliary stents in treating occluded primary metallic stents in malignant distal biliary obstruction. Surg Endosc. 2011;25(2):475\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatsinelos P, Beltsis A, Chatzimavroudis G, et al. Endoscopic management of occluded biliary uncovered metal stents: A multicenter experience. World J Gastroenterol. 2011;17(1):98\u0026ndash;104.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTham TCK, Vandervoort J, Wong RCK, Lichtenstein DR, Vannerman W, Libby ED. Management of occluded biliary Wallstents. Gut. 1998;42:703\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBueno JT, Gerdes H, Kurtz RC. Endoscopic management of occluded biliary Wallstents: a cancer center experience. Gastrointest Endosc. 2003;58:879\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRogart JN, Boghos A, Rossi F, Al-hashem H, Siddiqui UD. Analysis of endoscopic management of occluded metal biliary stents at a single tertiary care center. Gastrointest Endosc. 2008;68(4):676\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTogawa O, Kawabe T, Isayama H, Nakai Y. Management of Occluded Uncovered Metallic Stents in Patients With Malignant Distal Biliary Obstructions Using Covered Metallic Stents. J Clin Gastroenterol. 2008;42(5):546\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoon WJ, Ryu JK, Lee JW, et al. Endoscopic management of occluded metal biliary stents: Metal versus 10F plastic stents. World J Gastroenterol. 2010;16(42):5347\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRidtitid W, Rerknimitr R. Outcome of second interventions for occluded metallic stents in patients with malignant biliary obstruction. Surg Endosc. 2010;24:2216\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIsayama H, Hamada T, Fujisawa T, et al. TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage. Dig Endosc. 2024;(March):1\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKiriyama S, Kozaka K, Takada T, et al. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci. 2018;25:17\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhazi R, AbiMansour JP, Mahmoud T, et al. Uncovered Versus Fully-Covered Self-Expandable Metal Stents for the Management of Distal Malignant Biliary Obstruction. Gastrointest Endosc. 2023;\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShah T, Desai S, Haque M, Dakik H, Fisher D. Management of occluded metal stents in malignant biliary obstruction: similar outcomes with second metal stents compared to plastic stents. Dig Dis Sci. 2012;57(11):2765\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakai Y, Isayama H, Mukai T, Itoi T, Maetani I, Kawakami H. Impact of anticancer treatment on recurrent obstruction in covered metallic stents for malignant biliary obstruction. J Gastroenterol. 2013;48:1293\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"digestive-diseases-and-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ddsj","sideBox":"Learn more about [Digestive Diseases and Sciences](http://link.springer.com/journal/10620)","snPcode":"10620","submissionUrl":"https://submission.nature.com/new-submission/10620/3","title":"Digestive Diseases and Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Biliary tract neoplasms, Cholestasis, Self expandable metallic stents, Cholangiopancreatography, endoscopic retrograde, Jaundice, obstructive","lastPublishedDoi":"10.21203/rs.3.rs-4951976/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4951976/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground and Aim:\u003c/h2\u003e \u003cp\u003eEndoscopic biliary drainage with placement of a self-expanding metal stent (SEMS) is the preferred palliative treatment of malignant biliary obstruction. Recent advances in the treatment have prolonged survival, thus increasing the chance of recurrent biliary obstruction (RBO) after SEMS placement. The aim of this study was to compare different endoscopic approaches in patients with a SEMS and RBO, regarding clinical success and time to RBO.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included all patients with a SEMS placed because of malignant biliary strictures who underwent endoscopic retrograde cholangiopancreatography between January 2011 and December 2018. We evaluated the results of different endoscopic interventions to RBO, including insertion of a new SEMS, stent cleaning, and insertion of a plastic stent (PS).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFrom January 2011 to December 2018, 70 (22.4%) patients developed RBO requiring endoscopic reintervention (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;105 sessions). From the 105 ERCPs, technical success, clinical success and adverse events rates were 91,4%, 71,8%, 7,8%, respectively. Younger age (OR\u0026thinsp;=\u0026thinsp;1.11 95%CI: 1.03\u0026ndash;1.19) and the finding of a patent SEMS (OR\u0026thinsp;=\u0026thinsp;0.17 95%CI: 0.04\u0026ndash;0.08) were predictors of clinical failure (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006 and \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024, respectively). The mean patency time (in days) after endoscopic reintervention was greater for SEMSs than for PSs (417.2 [95% CI: 250.0\u0026ndash;584.4] \u003cem\u003evs\u003c/em\u003e 175.2 [95% CI: 124.0\u0026ndash;226.5], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eCorrect identification and treatment of the causal factor of RBO typically leads to technical and clinical success. Placement of a second SEMS provides longer patency compared to a plastic stent if ingrowth (overgrowth) occurs.\u003c/p\u003e","manuscriptTitle":"Results of endoscopic treatment of recurrent malignant biliary obstruction in patients with self-expanding metal stents","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-16 06:47:17","doi":"10.21203/rs.3.rs-4951976/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-23T16:02:32+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-23T10:55:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"338823536056985447781090732750092080249","date":"2024-09-11T04:25:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-07T17:47:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"26762965139398450402873076345173859249","date":"2024-08-30T01:25:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-27T22:54:40+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-27T19:15:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-23T02:19:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"Digestive Diseases and Sciences","date":"2024-08-21T13:33:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"digestive-diseases-and-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ddsj","sideBox":"Learn more about [Digestive Diseases and Sciences](http://link.springer.com/journal/10620)","snPcode":"10620","submissionUrl":"https://submission.nature.com/new-submission/10620/3","title":"Digestive Diseases and Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"2d255c7e-a7f0-4b30-ae2f-4d8b6fa0e99d","owner":[],"postedDate":"October 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T16:07:06+00:00","versionOfRecord":{"articleIdentity":"rs-4951976","link":"https://doi.org/10.1007/s10620-025-08853-y","journal":{"identity":"digestive-diseases-and-sciences","isVorOnly":false,"title":"Digestive Diseases and Sciences"},"publishedOn":"2025-01-30 15:58:11","publishedOnDateReadable":"January 30th, 2025"},"versionCreatedAt":"2024-10-16 06:47:17","video":"","vorDoi":"10.1007/s10620-025-08853-y","vorDoiUrl":"https://doi.org/10.1007/s10620-025-08853-y","workflowStages":[]},"version":"v1","identity":"rs-4951976","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4951976","identity":"rs-4951976","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}