Unilateral drainage and chemotherapy prolong the patency of a plastic stent placed above the sphincter of Oddi in patients with malignant hilar biliary obstruction.

Objectives: To evaluate the results of inside stent therapy for unresectable malignant hilar biliary obstruction and identify factors related to stent patency duration. Methods: Of 44 patients who underwent initial inside-stent placement above the sphincter of Oddi from April 2017 to December 2022, 42 with the resolution of jaundice (clinical success rate, 95.5%) were retrospectively analyzed. Univariate and multivariate logistic regression analysis identified factors associated with stent patency duration. Results: Univariate analysis revealed significant differences in the drainage method (406 days for unilateral drainage vs. 305 days for bilateral drainage of the right and left liver lobes, p = 0.022) with or without chemotherapy (406 days with vs. 154 days without, p = 0.038). Multivariate analysis (Cox proportional hazards analysis) revealed similar results, with unilateral drainage (p = 0.031) and chemotherapy (p = 0.048) identified as independent factors associated with prolonged stent patency. Early adverse events were observed in two patients (4.8%; one cholangitis, one pancreatitis). Conclusions: Inside-stent therapy was safely performed in patients with malignant hilar biliary obstruction. Simple unilateral drainage and chemotherapy may prolong stent patency.

Risk factors for recurrent biliary obstruction following suprapapillary placement of a plastic stent as preoperative biliary drainage for perihilar biliary malignancy.

BACKGROUND/PURPOSE: The usefulness of endoscopic biliary stenting by deploying a plastic stent suprapapillary, called inside-stent (IS) placement, as preoperative biliary drainage (PBD) for perihilar biliary malignancy (PHBM) has been demonstrated. This study investigated risk factors for recurrent biliary obstruction (RBO) after IS placement. METHODS: Consecutive patients with potentially resectable PHBM treated with IS placement as PBD between 2017 and 2023 at Nagoya University Hospital were retrospectively reviewed. RESULTS: A total of 157 patients were included, with RBO occurring in 34 (22%) patients. The non-RBO rates were 83% at 30 days, 77% at 60 days, and 57% at 90 days. The most common cause of RBO was stent occlusion (n = 14), followed by segmental cholangitis (n = 12) and stent migration (n = 8). Stent migration and occlusion occurred more frequently within and after 1 week post-stenting, respectively. In multivariate analysis, biliary infection before IS was the sole risk factor for RBO, with a hazard ratio of 2.404 (95% confidence interval 1.163-4.972; p = .018). This risk was reduced by temporary endoscopic nasobiliary drainage prior to definitive IS placement. CONCLUSIONS: Biliary infection before IS was identified as an independent risk factor for RBO in patients with PHBM with IS as PBD. CLINICAL TRIAL REGISTER: Clinical trial registration number: UMIN000025631.

Inside stent placement is suitable for preoperative biliary drainage in patients with perihilar cholangiocarcinoma.

BACKGROUND/PURPOSE: Endoscopic biliary stenting (EBS) is commonly used for preoperative drainage of localized perihilar cholangiocarcinoma (LPHC). This study retrospectively compared the utility of inside stent (IS) and conventional stent (CS) for preoperative EBS in patients with LPHC. METHODS: EBS was performed in 56 patients with LPHC. EBS involved the placement of a CS (n = 32) or IS (n = 24). Treatment outcomes were compared between these two groups. RESULTS: Preoperative recurrent biliary obstruction (RBO) occurred in 23 patients (71.9%) in the CS group and 7 (29.2%) in the IS group, with a significant difference (p = 0.002). The time to RBO (TRBO) was significantly longer in IS than in CS (log-rank: p < 0.001). The number of stent replacements was significantly lower in IS than CS [0.38 (0-3) vs. 1.88 (0-8), respectively; p < 0.001]. Gemcitabine-based neoadjuvant chemotherapy (NAC) was administered to 26 patients (46.4%). Among patients who received NAC, TRBO was longer in IS than in CS group (log-rank: p < 0.001). The IS group had a significantly shorter preoperative and postoperative hospital stay than the CS group (20.0 vs. 37.0 days; p = 0.024, and 33.5 vs. 41.5 days; p = 0.016).　 Both the preoperative and the postoperative costs were significantly lower in the IS group than in the CS group (p = 0.049 and p = 0.0034, respectively). CONCLUSION: Compared with CS, IS for preoperative EBS in LPHC patients resulted in fewer complications and lower re-intervention rates. The fact that the IS group had shorter preoperative and postoperative hospital stays and lower costs both preoperatively and postoperatively compared to the CS group may suggest that the use of IS has the potential to benefit not only the patient but also the healthcare system.

A Comparison of the Efficacy of Plastic Stent Placement Above and Across the Sphincter of Oddi for Benign Biliary Hilar Stricture.

We investigated the efficacy and safety of endoscopic plastic stent (PS) placement for hilar benign biliary strictures (BBSs) and compared cases with PS placement above (inside stent, IS) and across (usual stent, US) the sphincter of Oddi. Patients who underwent initial endoscopic PS placement for hilar BBSs between August 2012 and December 2021 were retrospectively analyzed. Hilar BBSs in 88 patients were investigated. Clinical success was achieved in 81 of these cases (92.0%), including 38 patients in the IS group and 43 patients in the US group. Unexpected stent exchange (uSE) before the first scheduled PS exchange occurred in 18 cases (22.2%). The median time from first stent placement to uSE was 35 days. There was no significant difference in the rate and median time to uSE between the two groups. The rates of adverse events such as pancreatitis or cholangitis in the two groups did not significantly differ. However, the rate of difficult stent removal in the IS group (15.8%) was significantly higher than that in the US group (0%) (p=0.0019). US placement is preferable to IS placement for scheduled stent exchange, as it offers the same effectiveness and risk of adverse events with easier stent removal.

Outcomes of Intraductal Placement of Covered Metal Stents for Unresectable Distal Malignant Biliary Obstruction.

Intraductal self-expandable metal stent (SEMS) placement may prolong stent patency by reducing duodenobiliary reflux. This study aimed to evaluate the efficacy and safety of this biliary drainage method in patients with unresectable distal malignant biliary obstruction (MBO). Consecutive patients with unresectable MBO who underwent initial covered SEMS placement between 2015 and 2022 were retrospectively reviewed. We compared the causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates between two biliary drainage methods (SEMSs placed above and across the papilla). A total of 86 patients were included (above: 38 and across: 48). Overall RBO rates (24% vs. 44%, p = 0.069) and median TRBO (11.6 months vs. 9.8 months, p = 0.189) were not significantly different between the two groups. The frequency of overall AEs was similar between the two groups in the entire cohort, but was significantly lower in patients with non-pancreatic cancer (6% vs. 44%, p = 0.035). Reintervention was successfully performed in the majority of patients in both groups. Intraductal SEMS placement was not associated with a prolonged TRBO in this study. Larger studies are warranted to further evaluate the benefit of intraductal SEMS placement.

Self-expandable metal stents have longer patency and less cholangitis than inside stents in malignant perihilar biliary obstruction.

Background and Aim: Outcomes of an inside stent (IS, a plastic stent placed above the sphincter of Oddi) versusa self-expandable metal stent (SEMS) for the drainage of malignant perihilar biliary obstruction has not been fully studied. The drainage strategy for perihilar biliary obstruction is difficult and should be clarified. Methods: Clinical data of patients who underwent biliary drainage for malignant perihilar biliary obstruction with IS or SEMS between April 2016 and September 2021 at our institution were retrospectively examined. Outcomes, including the time to recurrent biliary obstruction (TRBO), survival, and incidence of recurrent biliary obstruction with concomitant cholangitis (RBOC), were retrospectively evaluated. Results: Median TRBO was 280 (95% confidence interval [CI], 110-not available) days in the SEMS group (n = 24) and 113 (95% CI, 74-192) days in the IS group (n = 25) (P = 0.043). Among the patients with perihilar cholangiocarcinoma, the median survival of the two groups was comparable, namely 330 days in the SEMS group and 359 days in the IS group (P = 0.46). The incidence of RBOC at re-intervention was significantly higher in patients with ISs (83.9%) than in those with SEMSs (0%) (P = 0.00004). Conclusions: TRBO was significantly longer in the SEMS group. Regardless of whether SEMSs or ISs were placed during the first intervention, patient survival was similar. Using easily removable ISs first might be a reasonable option because TRBO with SEMSs was shorter than patient survival. Cholangitis is a problem associated with the placement of IS.

Possible reasons for the regrettable results of patency of an inside stent in endoscopic transpapillary biliary stenting.

Endoscopic biliary decompression is a minimally invasive procedure for cholestasis since the first endoscopic retrograde cholangiopancreatography-guided biliary stenting performed by Soehendra and Reynders-Frederix. Among the endoscopic biliary decompression, endoscopic transpapillary biliary stenting (EBS), is a mainstream choice and presently has two methods of placement: stenting above the sphincter of Oddi (SO) (suprapapillary) and stenting across the SO (transpapillary). Stent patency is the most important concern for patients, endoscopists and physicians because it can affect both the life prognosis and treatment schedule of patients. Biliary stent occlusion can occur because of several factors. Among them, direct food impaction, biofilm formation, and sludge formation play important roles and are presumed to be theoretically overcome by EBS above the SO. Thus, EBS above the SO is expected to result in a longer patency than EBS across the SO. In the literature, there have been six comparative studies on EBS for distal biliary obstruction in which the stent was placed above or across the SO, including two randomized controlled trials (RCTs) with negative results of stenting above the SO. With respect to EBS for hilar biliary obstruction, there have been no RCTs, whereas four retrospective comparative studies with negative results and four retrospective comparative studies showing positive results of stenting above the SO have been reported. In this review, we focused on EBS above and across the SO, and summarized the positive and negative results of the two types of stenting to promote effective clinical practice and to provide a basis for future studies.

Stent placement above the sphincter of Oddi is a useful option for patients with inoperable malignant hilar biliary obstruction.

BACKGROUND AND AIMS: Endoscopic biliary drainage (EBD) is essential for the management of malignant hilar biliary obstruction (MHBO). We prospectively evaluated the efficacy and safety of "inside-stent" therapy, where a plastic stent is placed above the sphincter of Oddi without endoscopic sphincterotomy, in patients with inoperable MHBO. METHODS: This study was a multicenter, single-blinded, randomized controlled trial at three centers. Patients with inoperable MHBO were enrolled in this study, and randomly assigned to receive an inside-stent or conventional-stent therapy. The primary endpoint was cumulative stent patency of the initial stent. The secondary endpoints were second stent patency, technical and clinical success rate, adverse events, re-intervention rate, and overall patient survival. RESULTS: Forty-three patients were randomly assigned to the inside-stent group (n = 21) or the conventional-stent group (n = 22). The median cumulative stent patency of the initial stent was 123 days in the inside-stent group and 51 days in the conventional-stent group (P = .031). For patients with the initial stent dysfunction in the conventional-stent group, the inside-stent was placed as a second stent, and its patency was significantly longer than that of the initial stent (P = .0001). The technical and clinical success rate, re-intervention rate, second stent patency, adverse events, and survival probability did not differ between the groups. CONCLUSIONS: Inside-stent therapy appears to be useful not only as an initial stent but also as a second stent for patients with inoperable MHBO. TRIAL REGISTRATION NUMBER: UMIN000004587.

A Prospective Multicenter Study of "Inside Stents" for Biliary Stricture: Multicenter Evolving Inside Stent Registry (MEISteR).

BACKGROUND: Endoscopic biliary stent placement is the standard of care for biliary strictures, but stents across the papilla are prone to duodenobiliary reflux, which can cause stent occlusion. Preliminary studies of "inside stents" placed above the papilla showed encouraging outcomes, but prospective data with a large cohort were not reported. METHODS: This was a prospective multicenter registry of commercially available inside stents for benign and malignant biliary strictures. Primary endpoint was recurrent biliary obstruction (RBO). Secondary endpoints were technical success of stent placement and removal, adverse events, and stricture resolution. RESULTS: A total of 209 inside stents were placed in 132 (51 benign and 81 malignant) cases with biliary strictures in 10 Japanese centers. During the follow-up period of 8.4 months, RBO was observed in 19% of benign strictures. The RBO rate was 49% in malignant strictures, with the median time to RBO of 4.7 months. Technical success rates of stent placement and removal were both 100%. The adverse event rate was 8%. CONCLUSION: This prospective multicenter study demonstrated that inside stents above the papilla were feasible in malignant and benign biliary strictures, but a randomized controlled trial is warranted to confirm its superiority to conventional stents across the papilla.

Utility of the inside stent as a preoperative biliary drainage method for patients with malignant perihilar biliary stricture.

BACKGROUND/PURPOSE: Appropriate preoperative biliary drainage (PBD) is extremely important in patients with operable malignant perihilar biliary strictures. The aim of this study was to clarify the utility of inside stents in PBD. METHODS: Eighty-one patients with malignant perihilar biliary stricture who underwent endoscopic nasobiliary drainage (ENBD) as the first PBD method were enrolled. Biliary stenting was performed in 61 patients during the study course (41 patients-inside stent implanted in the bile duct; 20 patients-conventional stent placed across the papilla of Vater). Twenty patients continued ENBD until surgery. Treatment outcomes were compared among the three groups. RESULTS: The re-intervention rate was significantly lower in the inside stent group than in the conventional stent group and ENBD group (9.8% vs 40% and 35%, P = .013 and .030, respectively), and the time to re-intervention was also significantly longer (log-rank: P = .004 and .041, respectively). Of the five patients in the inside stent group who underwent neoadjuvant chemotherapy, only one required re-intervention. There was no significant difference in the incidence of postoperative complications among the three groups. CONCLUSIONS: The inside stent may be a useful PBD method for patients with malignant perihilar biliary stricture.

The role of stent placement above the papilla (inside-stent) as a bridging therapy for perihilar biliary malignancy: an initial experience.

PURPOSE: Although endoscopic naso-biliary drainage (ENBD) is a popular preoperative biliary drainage (PBD) method for patients with perihilar biliary malignancy (PHBM), patient discomfort caused by the nasal tube remains a problem. This study aimed to analyze the safety and efficacy of PBD with the placement of a plastic stent above the papilla [inside-stent (IS)] as a bridging therapy. METHODS: The outcomes of 78 patients with potentially resectable PHBM, of whom 29 underwent IS placement and 49 underwent ENBD were evaluated. RESULTS: The stent-associated complication rates were not different between the two groups (7% in the IS group and 10% in the ENBD group, P = 0.621). Catheter dislocation occurred less frequently (0% vs. 22%, P = 0.016), and the median time to recurrent biliary obstruction was longer (not reached vs. 32 days, P = 0.039) in the IS group than in the ENBD group. Among the patients who underwent resection, their postoperative severe complication rates were not substantially different (26% vs. 25%, P = 0.923). CONCLUSION: IS placement is a possible alternative to ENBD as a bridge to a definitive operation for patients with resectable PHBM and a prospective trial to prove its feasibility and safety is therefore warranted.

Long-term outcomes of endoscopic treatment for duct-to-duct anastomotic strictures after living donor liver transplantation.

BACKGROUND AND AIMS: The anastomotic biliary stricture is a clinically important complication after living donor liver transplantation (LDLT) with a duct-to-duct anastomosis. Although endoscopic management of post-LDLT biliary strictures using balloon dilation (BD) and plastic stents (PSs) has provided acceptable short-term outcomes, long-term outcomes and prognostic factors for treatment success remain unclear. METHODS: We included 96 patients with post-LDLT biliary strictures who were endoscopically managed between 2003 and 2016. BD was utilized as a first-line treatment strategy, and PS placement was carried out for refractory cases. Potential prognostic factors for biliary stricture resolution were analysed using logistic regression analyses. RESULTS: Endoscopic treatment was technically successful in 84 patients (87.5%). The overall rate of biliary stricture resolution was 44.8% (43 of 96 patients) with a median follow-up duration of 90.9 months (interquartile range, 30.9-122.3 months). Bile duct kinking was associated with a lower rate of biliary stricture resolution (odds ratio, 0.33; 95% confidence interval, 0.13-0.87). After successful endoscopic treatment, biliary strictures recurred in 22 patients (57.9%) after BD, and in one patient (4%) after PS treatment. CONCLUSIONS: Despite a high technical success rate, endoscopic treatment only provided a low rate of resolution of anastomotic biliary strictures among LDLT patients and required prolonged treatment duration. Alternative strategies including the use of a covered metal stent should be evaluated to further improve the treatment outcomes of post-LDLT biliary strictures, particularly in those accompanied by the bile duct kinking.