Multicenter randomized trial of endoscopic papillary large balloon dilation without sphincterotomy versus endoscopic sphincterotomy for removal of bile duct stones: MARVELOUS trial.

BACKGROUND : Endoscopic papillary large balloon dilation (EPLBD) has been increasingly used for the management of large common bile duct (CBD) stones. Although EPLBD is often preceded by endoscopic sphincterotomy (EST), EPLBD alone without EST has been increasingly reported as an alternative to EST for large CBD stones. METHODS : This multicenter randomized trial was conducted at 19 Japanese institutions to compare the efficacy and safety of EPLBD alone versus EST for the removal of large (≥ 10 mm) CBD stones. The primary end point was complete stone removal in a single session. The secondary end points included: overall complete stone removal, lithotripsy use, procedure time, adverse events, and cost. RESULTS: 171 patients with large CBD stones were included in the analysis. The rate of single-session complete stone removal was significantly higher in the EPLBD-alone group than in the EST group (90.7 % vs. 78.8 %; P = 0.04). Lithotripsy use was significantly less frequent in the EPLBD group than in the EST group (30.2 % vs. 48.2 %; P = 0.02). The rates of early adverse events were comparable between the two groups: rates of overall adverse events were 9.3 % vs. 9.4 % and of pancreatitis were 4.7 % vs. 5.9 % in the EPLBD and EST groups, respectively. The procedure costs were $1442 vs. $1661 in the EPLBD and EST groups, respectively (P = 0.12). CONCLUSION : EPLBD without EST for the endoscopic treatment of large CBD stones achieved a significantly higher rate of complete stone removal in a single session compared with EST, without increasing adverse events.

Early pancreatic stent placement in wire-guided biliary cannulation: A multicenter retrospective study.

BACKGROUND AND AIM: Guidewire insertion to a pancreatic duct under wire-guided cannulation (WGC) during endoscopic retrograde cholangiopancreatography (ERCP) is associated with a high incidence of post-ERCP pancreatitis (PEP). Pancreatic stent placement followed by WGC (PS-WGC) is considered for these cases to reduce PEP. This study was aimed to examine the effectiveness of PS-WGC compared with repeated WGC. METHODS: The consecutive data of patients without history of ERCP who underwent ERCP for biliary intervention were retrospectively collected from five centers. Patients without guidewire insertion to the pancreatic duct were excluded. Pancreatic stent was immediately placed after guidewire insertion to the pancreatic duct in the PS-WGC group. The association between the method of biliary cannulation (PS-WGC or repeated WGC) and PEP was analyzed using multivariable logistic regression model. RESULTS: A total of 590 patients (183 in the PS-WGC and 407 in the repeated WGC group) were included. PS-WGC decreased PEP (8.7% vs 19%, P = 0.001) and improved its severity (moderate and severe PEP; 2.2% vs 6.4%, P = 0.04) compared with repeated WGC. PS-WGC was associated with reduction of PEP in the multivariable model (Odds ratio 0.31, P < 0.001). The rates of difficult cannulation and overall successful biliary cannulation were not different between the two groups (66% vs 70%, P = 0.39 and 98% vs 96%, P = 0.21 in the PS-WGC and repeated WGC group, respectively). CONCLUSIONS: Pancreatic stent placement followed by WGC reduced PEP in patients with guidewire insertion to the pancreatic duct during WGC for native papilla compared with repeated WGC.

Antireflux covered metal stent for nonresectable distal malignant biliary obstruction: Multicenter randomized controlled trial.

BACKGROUND AND AIM: An antireflux metal stent (ARMS) for nonresectable distal malignant biliary obstruction (MBO) may prevent recurrent biliary obstruction (RBO) as a result of duodenobiliary reflux and prolong time to RBO (TRBO). Superiority of ARMS over conventional covered self-expandable metal stents (SEMS) has not been fully examined. METHODS: We conducted a multicenter randomized controlled trial to examine whether TRBO of an ARMS with a funnel-shaped valve was longer than that of a covered SEMS in SEMS-naïve patients. We enrolled 104 patients (52 patients per arm) at 11 hospitals in Japan. Secondary outcomes included causes of RBO, adverse events, and patient survival. RESULTS: TRBO did not differ significantly between the ARMS and covered SEMS groups (median, 251 vs 351 days, respectively; P = 0.11). RBO as a result of biliary sludge or food impaction was observed in 13% and 9.8% of patients who received an ARMS and covered SEMS, respectively (P = 0.83). ARMS was associated with a higher rate of stent migration compared with the covered SEMS (31% vs 12%, P = 0.038). Overall rates of adverse events were 20% and 18% in the ARMS and covered SEMS groups, respectively (P = 0.97). No significant between-group difference in patient survival was observed (P = 0.26). CONCLUSIONS: The current ARMS was not associated with longer TRBO compared with the covered SEMS. Modifications including addition of an anti-migration system are required to use the current ARMS as first-line palliative treatment of distal MBO (UMIN-CTR clinical trial registration number: UMIN000014784).

International study of endoscopic management of distal malignant biliary obstruction combined with duodenal obstruction.

OBJECTIVE: Endoscopic transpapillary or endoscopic ultrasound (EUS)-guided stent placement is used for nonresectable distal malignant biliary obstruction. We conducted a retrospective study to evaluate endoscopic biliary drainage in patients with duodenal obstruction. METHODS: We included consecutive patients who underwent endoscopic biliary drainage combined with a duodenal stent at 16 referral centers in four Asian countries. The primary outcome was time to recurrent biliary obstruction (TRBO). We assessed TRBO according to the sequence of biliary and duodenal obstruction (group 1/2/3, biliary obstruction first/concurrent/duodenal obstruction first, respectively) or the location of duodenal obstruction (type I/II/III, proximal to/affecting/distal to the ampulla, respectively). We also evaluated functional success and adverse events. RESULTS: We included 110 patients (group1/2/3, 67/29/14 patients; type I/II/III, 45/46/19 patients; endoscopic retrograde cholangiopancreatography [ERCP]/EUS-guided choledocoduodenostomy/EUS-guided hepaticogastrostomy, 90/10/10 patients, respectively). The median TRBO of all cases was 450 days (interquartile range, 212-666 days) and functional success was achieved in 105 cases (95%). The TRBO did not differ significantly by the timing or location of duodenal obstruction (p = .30 and .79, respectively). The TRBO of metal stents (n = 96) tended to be longer compared with plastic stents (n = 14, p = .083). Compared with ERCP, EUS-guided biliary drainage was associated with a higher rate of adverse events. CONCLUSION: Transpapillary or transmural endoscopic biliary drainage with a duodenal stent was effective, irrespective of the timing or location of duodenal obstruction. A prospective study is required considering the tradeoff of technical success rate, stent patency, and adverse events (ClinicalTrials.gov number, NCT02376907).

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

BACKGROUND AND AIM: Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. METHODS: A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. RESULTS: Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. CONCLUSIONS: Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO.

A 19-Gauge Histology Needle Versus a 19-Gauge Standard Needle in Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Solid Lesions: A Multicenter Randomized Comparison Study (GREATER Study).

BACKGROUND: The necessity of histological analysis is increasing. A 19-gauge histology needle (PC19) in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has recently been developed and has shown high yields of tissue acquisition and histological diagnosis. AIMS: To compare the histological diagnostic yield in single-pass EUS-FNA for solid lesions using PC19 and a standard 19-gauge needle (EC19). PATIENTS AND METHODS: Consecutive patients with solid lesions were enrolled and underwent one pass with each of PC19 and EC19 for EUS-FNA with the randomized order of the needles. The primary endpoint was the histological diagnostic accuracy. The secondary endpoints were the feasibility, yield of histological core, cytological and overall diagnostic accuracies, and adverse events. Subgroup analysis was performed for the optimal situation with PC19. RESULTS: Of the 115 patients, 110 underwent EUS-FNA and five were excluded. EUS-FNA was performed from the esophagus in four, stomach in 80, or duodenum in 26. The final diagnosis was malignancy in 100 and benign in 10. The feasibility was 98.2 and 97.3% with PC19 and EC19, respectively (p = 1.00). The rate of presence of a histological core and the histological, cytological, and overall diagnostic accuracies for PC19 versus EC19 were 84.6 versus 80.9% (p = 0.593), 83.6 versus 73.6% (p = 0.099), 63.6 versus 56.4% (p = 0.335), and 90.0 versus 79.1% (p = 0.039), respectively. PC19 was favored in the trans-esophageal/gastric approaches to obtain a histological diagnosis (p = 0.013). Adverse events were observed in four patients. CONCLUSION: Single-pass EUS-FNA with PC19 was feasible and showed significantly higher overall diagnostic accuracy and an increased tendency towards histological diagnostic accuracy, especially with trans-esophageal/gastric FNA.

Gemcitabine and S-1 versus gemcitabine and cisplatin treatment in patients with advanced biliary tract cancer: a multicenter retrospective study.

Objective This study aimed to compare the safety and efficacy of the combination therapy of gemcitabine and S-1 (GS) versus gemcitabine and cisplatin (GC) in patients with advanced biliary tract cancer (BTC). Methods In this multicenter retrospective cohort study, a total of 212 patients with advanced BTC receiving GS (n = 125) or GC (n = 87) between July 2006 and August 2015 were analyzed. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective tumor response, and safety. Results Patient characteristics were well balanced between the two groups, except for tumor size (the baseline sum of the largest diameter of the tumor: 6.3 cm in the GS group vs. 8.6 cm in the GC group, p = 0.01). Although the response rate was higher in the GS group than in the GC group (28.8% vs. 10.3%, p = 0.01), the median PFS and OS were comparable between the two groups (PFS of 5.6 vs. 7.6 months, p = 0.74; OS of 12.4 vs. 9.2 months, p = 0.20, respectively). Stomatitis and skin rash were more frequently observed in the GS group, whereas anemia, thrombocytopenia, nausea, and renal toxicity were more commonly observed in the GC group. Conclusion This study demonstrates that GS and GC are similar with regard to their safety and efficacy in patients with advanced BTC. GS could serve as an alternative treatment for advanced BTC as a first-line chemotherapy.

Early use of double-guidewire technique to facilitate selective bile duct cannulation: the multicenter randomized controlled EDUCATION trial.

BACKGROUND AND STUDY AIMS: There are no guidelines for the timing of conversion from a single-guidewire to a double-guidewire technique to facilitate selective bile duct cannulation and reduce post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), when using wire-guided cannulation. We investigated whether early conversion to the double-guidewire method, at first unintentional insertion of a guidewire into the pancreatic duct, facilitated selective bile duct cannulation and reduced PEP compared with repeated single-guidewire attempts. PATIENTS AND METHODS: A multicenter prospective randomized controlled trial included 274 patients with a naive papilla, undergoing endoscopic retrograde cholangiography (ERC) using wire-guided cannulation in whom there was unintentional insertion of the guidewire into the pancreatic duct. With the guidewire still in the duct, patients were randomly assigned to undergo the double-guidewire technique or repeated single-wire cannulation. Main outcomes were success rates for selective bile duct cannulation and PEP frequency. RESULTS: Success rates for selective bile duct cannulation within 10 attempts and 10 minutes were 75 % and 70 %, respectively, for the early double-guidewire (EDG) and repeated single-guidewire (RSG) cannulation groups (relative rate 1.07, 95 % confidence interval [95 %CI] 0.93 - 1.24, P = 0.42). Corresponding final selective bile duct cannulation rates were 98 % and 97 % (relative rate 1.01, 95 %CI 0.97 - 1.05, P = 1.00). PEP rates were 20 % and 17 %, respectively, for the EDG and RSG cannulation groups (relative risk 1.17, 95 %CI 0.71 - 1.94, P = 0.53). Double-guidewire cannulation was more effective in patients with malignant biliary stricture (relative rate 1.36, 95 %CI 1.05 - 1.77, P = 0.02). CONCLUSIONS: During therapeutic ERC using wire-guided cannulation, converting to a double-guidewire technique neither facilitated selective bile duct cannulation nor decreased PEP incidence compared with repeated use of a single-wire technique.

Clinical outcomes of secondary gastroduodenal self-expandable metallic stent placement by stent-in-stent technique for malignant gastric outlet obstruction.

BACKGROUND AND AIM: To evaluate the efficacy and safety of secondary gastroduodenal stent placement after first stent dysfunction for malignant gastric outlet obstruction. METHODS: We conducted a retrospective analysis to investigate the efficacy and safety of secondary stent-in-stent gastroduodenal stent placement. RESULTS: Among 260 patients who had been treated with first gastroduodenal stent placement for malignant gastric outlet obstruction, 29 patients (11.2%) were treated with secondary gastroduodenal stent placement because of first stent dysfunction. Pancreatic cancer was the major primary cancer (55.2%). A WallFlex duodenal stent was the most frequently inserted stent both as a first stent (75.9%) and as a secondary stent (62.1%). There were 22 patients (75.9%) that received gastroduodenal stents at the bending site (supraduodenal angle or infraduodenal angle). Technical and clinical success rates were 100% and 86.2%, respectively. Median eating period was 3.0 months, and median survival time was 3.5 months. As for related complications, gastrointestinal perforation, insufficient stent expansion, tumor ingrowth, tumor overgrowth, and cholangitis were experienced in 13.8% (four cases), 6.9% (two cases), 6.9% (two cases), 3.4% (one case), and 3.4% (one case), respectively. CONCLUSION: Secondary gastroduodenal stent placement might be effective for managing first stent dysfunction in malignant gastric outlet obstruction. However, gastrointestinal perforation was the major complication.

Risk factors for covered metallic stent migration in patients with distal malignant biliary obstruction due to pancreatic cancer.

BACKGROUND AND AIM: Covered metallic stents (CMSs) were developed to overcome tumor ingrowth in uncovered metallic stents (UMSs) for malignant biliary obstruction, but superiority of CMSs over UMSs is still controversial due to the high migration rate in CMS. Therefore, we conducted this retrospective analysis to clarify risk factors for stent migration, including mechanical properties of CMSs. METHODS: Patients with unresectable pancreatic cancer, receiving CMS for distal malignant biliary obstruction in five tertiary care centers, were retrospectively studied. Univariate and multivariate analyses to identify prognostic factors for early (< 6 months) stent migration were performed using a proportional hazards model with death or stent occlusion without stent migration as a competing risk. Two mechanical properties were included in the analysis: axial force, the recovery force that leads to a CMS straightening, and radial force (RF), the expansion force against the stricture. RESULTS: Among 290 patients who received CMS placement for distal malignant biliary obstruction, stent migration rate was 15.2%. CMS migrated early (< 6 months) in 10.0% and distally in 11.7%, respectively. In the multivariate analysis, significant risk factors for early stent migration were chemotherapy (subdistribution hazard ratios [SHR] 4.46, P = 0.01), CMS with low RF (SHR 2.23, P = 0.03), and duodenal invasion (SHR 2.25, P = 0.02). CONCLUSION: CMS with low RF, chemotherapy, and duodenal invasion were associated with CMS migration from our study.

Metallic stent with high axial force as a risk factor for cholecystitis in distal malignant biliary obstruction.

BACKGROUND AND AIM: Tumor involvement to the orifice of cystic duct (OCD) is a risk factor for cholecystitis after self-expandable metallic stent (SEMS) placement, but its prevention is still difficult. We conducted this multicenter analysis to clarify a type of SEMS or a method to place SEMS which would decrease the incidence of cholecystitis after SEMS placement. METHODS: The incidence of cholecystitis was studied in consecutive patients receiving SEMS for distal malignant biliary obstruction in five tertiary care centers. Multiple logistic regression analysis was performed to evaluate risk factors for cholecystitis. RESULTS: A total of 376 patients who received SEMS placement for distal malignant biliary obstruction were analyzed. Tumor involvement to OCD was diagnosed in 25.3%. Overall incidence of cholecystitis was 6.9%. Cholecystitis was observed in 8.0% of 300 patients with covered SEMS, 16.8% of 95 patients with tumor involvement to OCD, 10.8% of 234 patients with SEMS of high axial force (AF), and 12.0% of 158 patients with SEMS length ≤ 60 mm. In the multivariate analysis, tumor involvement to OCD (odds ratio [OR] 5.40, P < 0.001), SEMSs with high AF (OR 5.33, P = 0.002), and SEMS length ≤ 60 mm (OR 3.19, P = 0.010) are risk factors. Among patients with tumor involvement to OCD, the incidence of cholecystitis in SEMS with high and low AF was 25.0% and 5.0%, respectively. CONCLUSION: This study with an expanded cohort reconfirmed tumor involvement to OCD as a risk factor for cholecystitis after SEMS placement. SEMS with low AF might decrease cholecystitis.

Transmural biliary drainage can be an alternative to transpapillary drainage in patients with an indwelling duodenal stent.

BACKGROUND: Self-expandable metal stents (SEMS) are widely utilized to relieve symptoms of malignant gastric outlet obstruction (GOO), but GOO is frequently complicated by nonresectable distal biliary obstruction. The optimal endoscopic approach to biliary drainage in this setting remains controversial and has yet to be resolved. AIMS: To compare the safety and efficacy of endoscopic ultrasound-guided transmural biliary drainage (EUS-BD) and transpapillary drainage in patients with an indwelling duodenal SEMS. METHODS: Patients who underwent EUS-BD or transpapillary drainage for distal malignant biliary obstruction with an indwelling duodenal SEMS between June 2007 and August 2012 at three Japanese tertiary referral centers were identified retrospectively. We compared times to stent dysfunction, causes of dysfunction, and procedural related complications between these two groups. RESULTS: Twenty patients were included in the study (7 EUS-BD and 13 transpapillary drainage). EUS-BD was performed via hepaticogastrostomy using a SEMS in three patients and via choledochoduodenostomy using a SEMS or a plastic stent in two patients each. Transpapillary drainage was performed using a SEMS in all patients. The stent patency rate in the EUS-BD group was higher than that in the transpapillary drainage group (100 vs. 71% at 1 month and 83 vs. 29% at 3 months, respectively). The rate of stent dysfunction in the EUS-BD group tended to be lower than that in the transpapillary group (14 vs. 54%; P = 0.157). Complication rates were similar between the groups (P = 1.000), with moderate bleeding in one patient in the EUS-BD group and mild pancreatitis in one patient in the transpapillary group. CONCLUSION: Endoscopic ultrasound-guided transmural biliary drainage is an alternative to transpapillary drainage in patients with an indwelling duodenal SEMS.

Estimation and comparison of cumulative incidences of biliary self-expandable metallic stent dysfunction accounting for competing risks.

BACKGROUND: Self-expandable metallic stent (SEMS) placement is widely carried out for distal malignant biliary obstruction, and survival analysis is used to evaluate the cumulative incidences of SEMS dysfunction (e.g. the Kaplan-Meier [KM] method and the log-rank test). However, these statistical methods might be inappropriate in the presence of 'competing risks' (here, death without SEMS dysfunction), which affects the probability of experiencing the event of interest (SEMS dysfunction); that is, SEMS dysfunction can no longer be observed after death. A competing risk analysis has rarely been done in studies on SEMS. PATIENTS AND METHODS: We introduced the concept of a competing risk analysis and illustrated its impact on the evaluation of SEMS outcomes using hypothetical and actual data. Our illustrative study included 476 consecutive patients who underwent SEMS placement for unresectable distal malignant biliary obstruction. RESULTS: A significant difference between cumulative incidences of SEMS dysfunction in male and female patients via theKM method (P = 0.044 by the log-rank test) disappeared after applying a competing risk analysis (P = 0.115 by Gray's test). In contrast, although cumulative incidences of SEMS dysfunction via the KM method were similar with and without chemotherapy (P = 0.647 by the log-rank test), cumulative incidence of SEMS dysfunction in the non-chemotherapy group was shown to be significantly lower (P = 0.031 by Gray's test) in a competing risk analysis. CONCLUSION: Death as a competing risk event needs to be appropriately considered in estimating a cumulative incidence of SEMS dysfunction, otherwise analytical results may be biased.

Novel antireflux covered metal stent for recurrent occlusion of biliary metal stents: a pilot study.

BACKGROUND: Feasibility of antireflux metal stent (ARMS), designed to prevent duodenobiliary reflux, was reported in patients with distal malignant biliary obstruction. In this prospective pilot study, we aimed to evaluate a newly designed ARMS as a reintervention for self-expandable metallic stent (SEMS) occlusion believed to be caused by duodenobiliary reflux. PATIENTS AND METHODS: Patients with non-resectable distal malignant biliary obstruction were included in whom a prior SEMS was occluded as a result of sludge or food impaction between March 2010 and January 2012 at two Japanese tertiary referral centers. The occluded SEMS were endoscopically removed, if possible, and subsequently replaced by a newly designed ARMS. We evaluated the technical success rate and complications of ARMS and compared the time to occlusion of ARMS with that of prior SEMS. RESULTS: A total of 13 patients were included. ARMS was successfully placed in all patients in a single procedure. No procedure-related complications were identified. ARMS occlusion occurred in two patients (15%), the causes of which were sludge in one patient and unknown in the other. ARMS migration occurred in four patients (31%). ARMS patency time was significantly longer than that of prior SEMS (median, not available vs 58 days; P = 0.039). CONCLUSIONS: This newly designed ARMS is a technically feasible, safe, and effective reintervention for SEMS occlusion as a result of sludge or food impaction. An anti-migration mechanism to improve the outcomes of ARMS should be considered.

Results of the Tokyo trial of prevention of post-ERCP pancreatitis with risperidone-2: a multicenter, randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Our previous study suggested that a combination of ulinastatin and risperidone reduced post-ERCP pancreatitis (PEP) compared with ulinastatin alone. OBJECTIVE: The aim of this study was to evaluate the efficacy of risperidone alone for prevention of PEP. DESIGN: A multicenter, randomized, placebo-controlled, double-blind clinical trial. SETTING: Two academic hospitals and 5 referral hospitals in Tokyo and Saitama, Japan. PATIENTS: Patients undergoing therapeutic or interventional-diagnostic ERCP. INTERVENTION: The patients were randomized to receive 2 mg of oral risperidone or oral placebo at 0.5 to 2 hours before ERCP. MAIN OUTCOME MEASUREMENTS: The primary endpoint was the incidence of PEP. Secondary endpoints were the incidence of hyperenzymemia and enzyme levels (amylase, pancreatic amylase, lipase). Risk factors for PEP were evaluated. RESULTS: We initially enrolled 500 patients in the study (250 in the risperidone group and 250 in the placebo group), but 17 (11 in the risperidone and 6 in the placebo group) were excluded after randomization. PEP developed in 24 patients (10.0%) in the risperidone group and 21 patients (8.6%) in the placebo group (P = .587). Serum amylase levels at 3 hours after ERCP were lower in the risperidone group (P = .007 in a single test of hypothesis, significance removed by Bonferroni correction for multiple testing). In multivariate analysis, a small papilla of Vater, total procedure time ≥40 minutes, and stenosis of the intrahepatic duct were significantly associated with PEP. LIMITATIONS: Multiplicity of study centers and a relatively wide time range of drug administration time. CONCLUSION: Risperidone did not show a benefit in prevention of PEP in this trial. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT000004592.).

Duodenal metal stent placement is a risk factor for biliary metal stent dysfunction: an analysis using a time-dependent covariate.

BACKGROUND: Although the combination of biliary and duodenal self-expandable metal stents (SEMS) is useful, the exacerbating effect of duodenal SEMS placement on biliary SEMS has not been documented. We conducted a multicenter retrospective study to evaluate the effect of duodenal SEMS placement on biliary SEMS. METHODS: Patients who underwent first-time biliary SEMS placement for a distal malignant biliary obstruction between September 1994 and November 2010 were included. Time to dysfunction of biliary SEMS was analyzed to identify risk factors for biliary SEMS dysfunction. Duodenal SEMS placement was analyzed as a time-dependent covariate. RESULTS: In total, 410 eligible patients were identified. Duodenal SEMS were placed in 33 patients (8 %). The median time to dysfunction of biliary SEMS was 170 days. Male gender (hazard ratio 1.37, 95 % confidence interval 1.03-1.83, P = 0.029) and duodenal SEMS placement (hazard ratio 2.00, 95 % confidence interval 1.16-3.45, P = 0.013) were risk factors in the multivariate Cox model. In patients undergoing duodenal SEMS, biliary SEMS dysfunction was observed in 17 (52 %) with a median time to dysfunction of 64 days after duodenal SEMS placement. As many as 60 % of the patients with biliary SEMS dysfunction after duodenal SEMS placement needed permanent percutaneous transhepatic biliary external drainage. CONCLUSIONS: Duodenal SEMS placement is a risk factor for biliary SEMS dysfunction. Alternative methods for biliary drainage should be considered for better biliary drainage in patients with a gastric outlet obstruction.

Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine.

Gemcitabine is widely used for the treatment of advanced biliary tract cancer (BTC) as first-line chemotherapy. However, there is no standard chemotherapy for patient with advanced BTC refractory to gemcitabine. We conducted a multicenter phase II study of S-1 monotherapy as second-line chemotherapy for patients with advanced BTC that were refractory to gemcitabine. S-1 was administered orally at a dose of 80 mg/m(2) for 28 days, followed by 14 days of rest. This regimen was repeated every 6 weeks. Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0. Twenty-two patients were enrolled between March 2007 and January 2010, with 14 patients (64%) representing cases of recurrence after surgery. The overall response rate was 22.7%, and the overall disease control rate was 50.0%. The median overall survival time was 13.5 months (95% CI, 7.1-23.1 months) and the median time-to-progression was 5.4 months (95% CI, 2.6-17.2 months). Grade 3/4 toxicities included neutropenia (5%) and anemia (5%). The most common non-hematological toxicities were nausea (27%), anorexia (55%), and pigmentation (32%). In conclusion, S-1 monotherapy is feasible and moderately efficacious second-line chemotherapy for advanced BTC.

Management of malignant gastric outlet obstruction with a modified triple-layer covered metal stent.

BACKGROUND: A high incidence of migration with covered metal stents has been reported in malignant gastric outlet obstruction (GOO). A newly modified, partially covered, triple-layer nitinol stent was developed that has a longer uncovered portion (5-15 mm) to prevent stent migration. OBJECTIVE: To estimate the efficacy and safety of the modified covered, triple-layer metal stent. DESIGN: Multicenter, prospective cohort study. SETTING: Three tertiary referral centers. PATIENTS: Fifty consecutive patients (26 with pancreatic carcinoma, 14 with gastric carcinoma, 9 with cholangiocarcinoma, 1 with a metastatic node) who presented with symptomatic unresectable malignant GOO between April 2007 and March 2010. INTERVENTIONS: Endoscopic placement of the modified covered, triple-layer metal stent. MAIN OUTCOME MEASUREMENTS: The primary endpoint was to improve the GOO scoring system (GOOSS) score. Secondary endpoints were success rate, patency, and complications. RESULTS: The median GOOSS score improved significantly (P < .0001) after stenting (from 0 to 3). The technical and clinical success rates were 100% and 90%, respectively. Stent occlusion by tumor overgrowth or ingrowth at the uncovered portion developed in 5 patients (10%). Asymptomatic stent migration occurred in 3 patients (6%) receiving chemotherapy at 95, 230, and 553 days after stent placement, but these patients tolerated solid food 68, 260, and 142 days after stent migration, respectively. Other complications occurred in 1 patient with insufficient expansion, cholangitis, and pancreatitis. No procedure-related deaths occurred. LIMITATIONS: A single-arm study in tertiary-care centers. CONCLUSIONS: The modified covered, triple-layer metal stent was effective and safe for managing malignant GOO and can prevent tumor ingrowth and stent migration. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000004566.).

Comparison of partially covered nitinol stents with partially covered stainless stents as a historical control in a multicenter study of distal malignant biliary obstruction: the WATCH study.

BACKGROUND: Covered self-expandable metal stents (CSEMSs) were developed to prevent tumor ingrowth, but stent migration is one of the problems with CSEMSs. OBJECTIVE: To evaluate a new, commercially available CSEMS with flared ends and low axial force compared with a commercially available CSEMS without the anti-migration system and high axial force. DESIGN: Multicenter, prospective study with a historical cohort. SETTING: Twenty Japanese referral centers. PATIENTS: This study involved patients with unresectable distal malignant biliary obstruction. INTERVENTION: Placement of a new, commercially available, partially covered SEMS. MAIN OUTCOME MEASUREMENTS: Recurrent biliary obstruction rate, time to recurrent biliary obstruction, stent-related complications, survival. RESULTS: Between April 2009 and March 2010, 141 patients underwent partially covered nitinol stent placement, and between May 2001 and January 2007, 138 patients underwent placement of partially covered stainless stents as a historical control. The silicone cover of the partially covered nitinol stents prevented tumor ingrowth. There were no significant differences in survival (229 vs 219 days; P = .250) or the rate of recurrent biliary obstruction (33% vs 38%; P = .385) between partially covered nitinol stents and partially covered stainless stents. Stent migration was less frequent (8% vs 17%; P = .019), and time to recurrent biliary obstruction was significantly longer (373 vs 285 days; P = .007) with partially covered nitinol stents. Stent removal was successful in 26 of 27 patients (96%). LIMITATIONS: Nonrandomized, controlled trial. CONCLUSION: Partially covered nitinol stents with an anti-migration system and less axial force demonstrated longer time to recurrent biliary obstruction with no tumor ingrowth and less stent migration.

Risk factors for pancreatitis following transpapillary self-expandable metal stent placement.

BACKGROUND: Pancreatitis is one of complications after self-expandable metal stent (SEMS) placement. The purpose of this study was to evaluate risk factors for pancreatitis after endoscopic SEMS placement for malignant biliary obstruction (MBO). METHODS: We retrospectively reviewed 370 consecutive patients who underwent initial transpapillary SEMS placement for biliary decompression. The characteristics of inserted SEMSs were classified according to axial and radial force. RESULTS: Pancreatitis following SEMS insertion was observed in 22 patients (6%). All of them were mild according to consensus criteria. Univariate analysis indicated that injections of contrast into the pancreatic duct (frequency of pancreatitis, 10.3%), the placement of an SEMS with high axial force (8.3%), and nonpancreatic cancer (16.1%) significantly contributed to the development of pancreatitis, whereas female gender, a younger age, a covered SEMS, and a SEMS with high radial force or without a biliary sphincterotomy did not. In a multivariate risk model, SEMSs with high axial force (odds ratio [OR], 3.69; p = 0.022) and nonpancreatic cancer (OR, 5.52; p < 0.001) were significant risk factors for pancreatitis. CONCLUSIONS: SEMSs with high axial force and an etiology of MBO other than pancreatic cancer were strongly associated with a high incidence of pancreatitis following transpapillary SEMS placement in patients with distal MBO.