TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage.

The consensus-based TOKYO criteria were proposed as a standardized reporting system for endoscopic transpapillary biliary drainage. The primary objective was to address issues arising from the inconsistent reporting of stent outcomes across studies, which has complicated the comparability and interpretation of study results. However, the original TOKYO criteria were not readily applicable to recent modalities of endoscopic biliary drainage such as biliary drainage based on endoscopic ultrasound or device-assisted endoscopy. There are increasing opportunities for managing hilar biliary obstruction and benign biliary strictures through endoscopic drainage. Biliary ablation has been introduced to manage benign and malignant biliary strictures. In addition, the prolonged survival times of cancer patients have increased the importance of evaluating overall outcomes during the period requiring endoscopic biliary drainage rather than solely focusing on the patency of the initial stent. Recognizing these unmet needs, a committee has been established within the Japan Gastroenterological Endoscopy Society to revise the TOKYO criteria for current clinical practice. The revised criteria propose not only common reporting items for endoscopic biliary drainage overall, but also items specific to various conditions and interventions. The term "stent-demanding time" has been defined to encompass the entire duration of endoscopic biliary drainage, during which the overall stent-related outcomes are evaluated. The revised TOKYO criteria 2024 are expected to facilitate the design and reporting of clinical studies, providing a goal-oriented approach to the evaluation of endoscopic biliary drainage.

Drainage for fluid collections post pancreatic surgery and acute pancreatitis: similar but different?

Postoperative pancreatic fistulas (POPFs) are common adverse events that occur after pancreatic surgery. Endoscopic ultrasonography (EUS)-guided drainage (EUS-D) is a first-line treatment, similar to that for pancreatic fluid collection (PFCs) after acute pancreatitis. However, some POPFs do not develop fluid collections depending on the presence or location of the surgical drain, whereas others develop fluid collections, such as postoperative fluid collections (POPFCs). Although POPFCs are similar to PFCs, the strategy and modality for POPF management need to be modified according to the presence of fluid collections, surgical drains, and surgical type. As discussed for PFCs, the indications, timing, and selection of interventions or stents for EUS-D have not been fully elucidated for POPFs. In this review, we discuss the management of POPFs and POPFCs in comparison with PFCs due to acute pancreatitis and summarize the topics that should be addressed in future studies.

EUS-guided hepaticogastrostomy versus EUS-guided hepaticogastrostomy with antegrade stent placement in patients with unresectable malignant distal biliary obstruction: a propensity score-matched case-control study.

BACKGROUND AND AIMS: EUS-guided hepaticogastrostomy (EUS-HGS) is a rescue procedure when ERCP fails. Peritonitis and recurrent biliary obstruction (RBO) are adverse events (AEs) associated with EUS-HGS. Antegrade stent placement across a malignant distal biliary obstruction (DBO) followed by EUS-HGS (EUS-HGAS) creates 2 biliary drainage routes, potentially reducing peritonitis and prolonging time to RBO (TRBO). We compared the outcomes of the 2 techniques. METHODS: Data of consecutive patients with malignant DBO who underwent attempted EUS-HGS or EUS-HGAS across 5 institutions from January 2014 to December 2020 were retrospectively analyzed. A matched cohort of patients was obtained using 1-to-1 propensity score matching. The primary outcome was TRBO, and secondary outcomes were AEs except for RBO and overall survival. RESULTS: Among 360 patients, 283 (176 and 107 in the HGS and HGAS groups, respectively) were eligible. The matched cohorts included 81 patients in each group. AEs developed in 10 (12.3%) and 15 (18.5%) patients (P = .38) in the HGS and HGAS groups, respectively. RBO occurred in 18 and 2 patients in the HGS and HGAS groups, respectively (P < .001). TRBO was significantly longer in the HGAS group (median, 194 days vs 716 days; hazard ratio, .050; 95% confidence interval, .0066-.37; P < .01). However, no significant differences occurred in overall survival between the groups (median, 97 days vs 112 days; hazard ratio, .97; 95% confidence interval, .66-1.4; P = .88). CONCLUSIONS: EUS-HGAS extended TRBO compared with EUS-HGS, whereas AEs, except for RBO and overall survival, did not differ. The longer TRBO of EUS-HGAS could benefit patients with longer life expectancy.

Early versus delayed EUS-guided drainage for postoperative pancreatic fluid collections: a systematic review and meta-analysis.

BACKGROUND: Postoperative pancreatic fluid collections (POPFCs) are common adverse events (AEs) after pancreatic surgery and may need interventions. Endoscopic ultrasound (EUS)-guided drainage for POPFCs is increasingly reported, but its appropriate timing has not been fully elucidated. The aim of this meta-analysis was to evaluate treatment outcomes of POPFCs according to the timing of EUS-guided drainage. METHODS: Using PubMed, Embase, Web of Science, and the Cochrane database, we identified clinical studies published until December 2022 with data comparing outcomes of early and delayed EUS-guided drainage for POPFCs. We pooled data on AEs, mortality, and technical and clinical success rates, using the random-effects model. RESULTS: From 1415 papers identified in the initial literature search, we identified 6 retrospective studies, including 128 and 107 patients undergoing early and delayed EUS-guided drainage for POPFCs. The threshold of early and delayed drainage ranged from 14 to 30 days. Distal pancreatectomy was the major cause of POPFCs, ranging from 44 to 100%. The pooled odds ratio (OR) for AEs was 0.81 (95% confidence interval [CI] 0.40-1.64, P = 0.55) comparing early to delayed drainage. There was no procedure-related mortality. Technical success was achieved in all cases and a pooled OR of clinical success was 0.60 (95% CI 0.20-1.83, P = 0.37). CONCLUSION: POPFCs can be managed by early EUS-guided drainage without an increase in AEs.

Endoscopic Ultrasound-Guided Gastrojejunostomy for Malignant Afferent Loop Syndrome Using a Fully Covered Metal Stent: A Multicenter Experience.

BACKGROUND: Endoscopic-ultrasound-guided gastrojejunostomy (EUS-GJ) can be a new alternative for patients with malignant afferent loop syndrome (MALS). However, a fully covered self-expandable metal stent (FCSEMS) has not been well investigated in this setting. METHODS: This is a multicenter retrospective cohort study. Consecutive patients that underwent EUS-GJ using a FCSEMS for MALS between April 2017 and November 2022 were enrolled. Primary outcomes were technical and clinical success rates. Secondary outcomes were adverse events, recurrent symptoms, and overall survival. RESULTS: Twelve patients (median age: 67.5 years (interquartile range: 58-74.8); 50% male) were included. The most common primary disease and type of previous surgery were pancreatic cancer (67%) and pancreatoduodenectomy (75%), respectively. Technical success and clinical success were achieved in all patients. Procedure-related adverse events occurred in one patient (8%) with mild peritonitis. During a median follow-up of 96.5 days, one patient (8%) had recurrent symptoms due to the EUS-GJ stent dysfunction; including biliary events unrelated to the EUS-GJ stent, five patients (42%) had recurrent events. The median overall survival was 137 days. Nine patients (75%) died due to disease progression. CONCLUSIONS: EUS-GJ with a FCSEMS seems safe and effective for MALS with high technical and clinical success rates and an acceptable recurrence rate.

A pilot study of Spring Stopper Stents: Novel partially covered self-expandable metallic stents with anti-migration properties for EUS-guided hepaticogastrostomy.

Background and Objectives: EUS-guided hepaticogastrostomy (EUS-HGS) is an effective salvage procedure when conventional endoscopic transpapillary biliary drainage is difficult or fails. However, the risk of stent migration into the abdominal cavity has not been resolved completely. In this study, we evaluated a newly developed partially covered self-expandable metallic stent (PC-SEMS) that has a spring-like anchoring function on the gastric side. Methods: This retrospective pilot study took place at four referral centers in Japan between October 2019 and November 2020. We enrolled 37 cases consecutively who underwent EUS-HGS for unresectable malignant biliary obstruction. Results: The rates of technical and clinical success were 97.3% and 89.2%, respectively. Technical failures included one case in which the stent was dislocated during the removal of the delivery system, requiring additional EUS-HGS on another branch. Early adverse events (AEs) were observed in four patients (10.8%): two with mild peritonitis (5.4%) and one each (2.7%) with fever and bleeding. No late AEs were observed during the mean follow-up period of 5.1 months. All recurrent biliary obstructions (RBOs) were stent occlusions (29.7%). The median cumulative time to RBO was 7.1 months (95% confidence interval, 4.3 to not available). Although stent migration in which the stopper was in contact with the gastric wall on follow-up computed tomography was observed in six patients (16.2%), no migration was observed. Conclusions: The newly developed PC-SEMS is feasible and safe for the EUS-HGS procedure. The spring-like anchoring function on the gastric side is an effective anchor preventing migration.

Clinical Advances in the Diagnosis and Treatment of Biliary Tract Diseases.

Although the biliary tract is a small organ, it is diverse in location (intrahepatic bile ducts, extrahepatic bile ducts, gallbladder, and ampulla) and disease (including benign and malignant), thus a multidisciplinary approach involving endoscopists, surgeons, oncologists, radiologists, and infectious disease specialists is often required to treat biliary tract disease [...].

Early versus delayed interventions for necrotizing pancreatitis: A systematic review and meta-analysis.

Objectives: Interventions for necrotizing pancreatitis are generally postponed until 4 weeks after the onset of acute pancreatitis, but there remains controversy about whether we should always wait >4 weeks or can intervene early when necessary. This meta-analysis was conducted to evaluate treatment outcomes of necrotizing pancreatitis according to the cut-off defined in the revised Atlanta classification (≤4 vs. >4 weeks). Methods: Using PubMed, Web of Science, and the Cochrane database, we identified clinical studies published until March 2022 with data comparing outcomes of early and delayed interventions of necrotizing pancreatitis. We pooled data on adverse events, mortality, technical and clinical success rates, and needs for necrosectomy and open surgery, using the random-effects model. Results: We identified 11 retrospective studies, including 775 patients with early interventions and 725 patients with delayed interventions. Patients with early interventions tended to be complicated by organ failure. The rate of adverse events was comparable (OR 1.41, 95% CI 0.66-3.01; p = 0.38) but the rate of mortality was significantly higher (OR 1.70, 95% CI 1.21-2.40; p < 0.01) in early interventions. Technical success rates were similarly high but clinical success rates tended to be low (OR 0.39, 95% CI 0.15-1.00; p = 0.05) in early interventions, though not statistically significant. Pooled ORs for necrosectomy and open surgery were 2.14 and 1.23, respectively. Conclusions: Early interventions for necrotizing pancreatitis were associated with higher mortality rates and did not reduce adverse events or improve clinical success. However, our results should be confirmed in prospective studies.

Supportive treatment during the periprocedural period of endoscopic treatment for pancreatic fluid collections: a critical review of current knowledge and future perspectives.

Pancreatic fluid collections (PFCs) commonly develop as complications of acute pancreatitis and ductal disruption due to chronic pancreatitis. In the revised Atlanta classification, PFCs were classified based on the presence of necrosis and duration following the onset of acute pancreatitis. Interventions are required in cases of symptomatic pancreatic pseudocysts or walled-off necrosis (WON). In the management of these PFCs, endoscopic ultrasound-guided transluminal drainage and subsequent direct endoscopic necrosectomy for WON are increasingly utilized as less invasive treatment modalities compared to surgical debridement. To date, researchers have focused predominantly on the technical aspects of endoscopic therapy for symptomatic PFCs. Given the poor physical condition of patients receiving endoscopic treatment for PFCs, systemic support may have a substantial impact on the short- and long-term outcomes of these patients. A multidisciplinary approach is required to improve the clinical outcomes of patients with infected PFCs and their associated comorbidities. However, non-interventional support during the periprocedural period of endoscopic treatment of PFCs has not been fully discussed, and there have been considerable variations in the selection of treatment options between endoscopists and centers. To address these unmet needs in the clinical management of PFCs and promote future research to improve the clinical outcomes, we conducted a review of the literature within a multicenter consortium of expert endoscopists with specific expertise in the endoscopic treatment of PFCs. In this review, we summarize the current evidence on non-interventional supportive care (e.g., continuous lavage, medications, nutritional support, and antimicrobials) and propose potential topics for future research.

The Feasibility of Whole-Liver Drainage with a Novel 8 mm Fully Covered Self-Expandable Metal Stent Possessing an Ultra-Slim Introducer for Malignant Hilar Biliary Obstructions.

BACKGROUND: In the case of an unresectable malignant hilar biliary obstruction (MHBO), the optimal drainage method has not yet been established. Recently, an 8 mm, fully covered, self-expandable metal stent (FCSEMS) with an ultra-slim introducer has become available. In this article, the results of whole-liver drainage tests using this novel FCSEMS for MHBO are reported. METHODS: Unresectable MHBOs up to Bismuth IIIa with strictures limited to the secondary branches were eligible. The proximal end of the stent was placed in such a way as to avoid blocking the side branches, and the distal end was placed above the papilla when possible. Consecutive patients treated between April 2017 and January 2021 were retrospectively analyzed. The technical and functional success rates, rates and causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), revision for RBO, and adverse events (AEs) were evaluated. RESULTS: Eleven patients (Bismuth I/II/IIIa: 1/7/3) were enrolled. Two stents were placed in nine patients and three were placed in two patients. Both the technical and functional success rates were 100%. RBO occurred in four (36%) patients due to sludge formation. Revision was performed for three patients, with the successful removal of all stents. The median TRBO was 187 days, and no late AEs other than the RBO occurred. Regarding the distal position of the stent, the RBO rate was significantly lower (14.3% vs. 75%, p = 0.041) and the cumulative TRBO was significantly longer (median TRBO: not reached vs. 80 days, p = 0.031) in the case of the placement above the papilla than the placement across the papilla. CONCLUSION: For unresectable MHBOs of Bismuth I, II, and IIIa, whole-liver drainage with a novel 8 mm FCSEMS possessing an ultra-slim introducer was feasible and potentially safe, with favorable stent patency. Placement above the papilla might be preferrable to placement across the papilla.

Practical Tips for Safe and Successful Endoscopic Ultrasound-Guided Hepaticogastrostomy: A State-of-the-Art Technical Review.

Currently, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is widely performed worldwide for various benign and malignant biliary diseases in cases of difficult or unsuccessful endoscopic transpapillary cholangiopancreatography (ERCP). Furthermore, its applicability as primary drainage has also been reported. Although recent advances in EUS systems and equipment have made EUS-HGS easier and safer, the risk of serious adverse events such as bile leak and stent migration still exists. Physicians and assistants need not only sufficient skills and experience in ERCP-related procedures and basic EUS-related procedures such as fine needle aspiration and pancreatic fluid collection drainage, but also knowledge and techniques specific to EUS-HGS. This technical review mainly focuses on EUS-HGS with self-expandable metal stents for unresectable malignant biliary obstruction and presents the latest and detailed tips for safe and successful performance of the technique.

A safe sequential treatment approach for patients who have acute cholecystitis with severe inflammation: Transmural gallbladder drainage followed by laparoscopic cholecystectomy under the guidance of fluorescence imaging.

INTRODUCTION: For patients who have acute severe cholecystitis, urgent/early biliary drainage followed by delayed/elective laparoscopic cholecystectomy is recommended according to the Tokyo Guidelines 2018. Percutaneous transhepatic gallbladder drainage is an established technique. Recently, transmural gallbladder drainage under the guidance of endoscopic ultrasonography (EUS-GBD) was reported as a safe alternative. During surgery, fluorescence imaging using indocyanine green (ICG) has been increasingly used for visualizing the bile ducts. Herein, we report a sequential treatment approach which ensures safety without impairing normal activities before cholecystectomy: EUS-GBD followed by laparoscopic cholecystectomy using ICG fluorescence imaging. MATERIALS AND SURGICAL TECHNIQUE: A 66-year-old man with acute cholecystitis underwent urgent EUS-GBD and had the drainage tube placement through the duodenum into the gallbladder. During 2.5 months of the waiting period, he had no clinical troubles. After insertion of a laparoscope, we found a structure between the gallbladder and the duodenum. We injected 0.025 mg/mL of ICG into the nasobiliary drainage tube (placed in the gallbladder through the duodenum) and confirmed that the structure was a fistula. After removing the tube, the fistula was divided using a surgical stapler under the guidance of fluorescence imaging. The cystic and common bile ducts were also clearly visualized as fluorescence. DISCUSSION: We reported a safe sequential treatment approach for the patient who required biliary drainage: EUS-GBD followed by laparoscopic cholecystectomy under the guidance of ICG fluorescence imaging. This sequential approach may improve patients' satisfaction with respect to quality of life during the waiting period and may ensure the safety of laparoscopic cholecystectomy.

A prospective multicenter study of endoscopic ultrasound-guided fine needle biopsy using a 22-gauge Franseen needle for pancreatic solid lesions.

BACKGROUND AND AIM: While encouraging data of endoscopic ultrasound (EUS)-guided fine-needle biopsy (EUS-FNB) using a 22-gauge Franseen needle have been reported, large-scale data of per pass and quantitative analyses are still lacking. METHODS: This was a multicenter prospective study of EUS-FNB using the 22-gauge Franseen needle for a pancreatic solid lesion. Cytological and histological analyses per pass were evaluated and semi-quantitative analyses were performed on core tissue and blood contamination. Primary end-point was diagnostic accuracy per session. Prognostic factors were analyzed for diagnostic accuracy, sensitivity, core tissue, and blood contamination. RESULTS: A total of 629 passes were performed in 244 cases at 14 centers between 2018 and 2019. The median tumor size was 29 mm, and the puncture was transduodenal in 43%. The median pass number was 2. Diagnostic accuracy per session, at a first pass, and per pass were 93%, 90%, and 88%. In 198 cases with pancreatic cancer, diagnostic sensitivity per session, at a first pass, and per pass were 94%, 89%, and 89%. The rates of core tissue score of 4 and blood contamination score of 3 were 50% and 47%. The adverse event rate was 1.6%. In the multivariate analysis, tumor size ≤20 mm (odds ratio [OR] of 0.46, P = 0.03), transduodenal puncture (OR of 0.53, P = 0.04), and suction (OR of 0.16, P = 0.01) were associated with lower diagnostic accuracy. CONCLUSIONS: The EUS-FNB using the 22-gauge Franseen needle for pancreatic solid lesions showed high per pass and overall diagnostic accuracy.

Unilateral versus Bilateral Endoscopic Nasobiliary Drainage and Subsequent Metal Stent Placement for Unresectable Malignant Hilar Obstruction: A Multicenter Randomized Controlled Trial.

(1) Background: Endoscopic management of hilar biliary obstruction is still challenging. Compared with unilateral drainage, bilateral drainage could preserve larger functional liver volume and potentially improve clinical outcomes. To evaluate the effectiveness of bilateral drainage, we conducted this multicenter randomized controlled study. (2) Methods: Patients with unresectable malignant hilar biliary obstruction were assigned to unilateral or bilateral group. At first, patients underwent endoscopic nasobiliary drainage (ENBD), and subsequently underwent self-expandable metallic stent (SEMS) deployment. Primary outcomes were the functional success rate of ENBD and time to recurrent biliary obstruction (TRBO) after SEMS deployment. (3) Results: During the study period, 38 and 39 patients were enrolled in the unilateral and bilateral groups. The functional success rate was similar in the uni- and bi-ENBD group (57% vs. 56%; p = 0.99), but the rate of additional drainage was higher in uni-ENBD group. Although TRBO and overall survival time after SEMS deployment were not different between the groups (p = 0.11 and 0.78, respectively), the incidence of early adverse events tended to be higher in the bi-SEMS group (5.3% vs. 28%; p = 0.11). (4) Conclusions: Our study failed to demonstrate the superiority of bilateral over unilateral biliary drainage in terms of functional success rate and TRBO.

A Proposed Algorithm for Endoscopic Ultrasound-Guided Rendezvous Technique in Failed Biliary Cannulation.

BACKGROUND: The selection of an approach route in endoscopic ultrasound-guided rendezvous (EUS-RV) for failed biliary cannulation is complicated. We proposed an algorithm for EUS-RV. METHODS: We retrospectively evaluated consecutive EUS-RV cases between April 2017 and July 2020. Puncturing the distal extrahepatic bile duct (EHBD) from the duodenal second part (D2) (DEHBD/D2 route) was attempted first. If necessary, puncturing the proximal EHBD from the duodenal bulb (D1) (PEHBD/D1 route), puncturing the left intrahepatic bile duct (IHBD) from the stomach (LIHBD/S route), or puncturing the right IHBD from the D1 (RIHBD/D1 route) were attempted in this order. RESULTS: A total of 16 patients were included. The DEHBD/D2 route was used in 10 (62.5%) patients. The PEHBD/D1 route was attempted in five (31.3%) patients, and the biliary puncture failed in one patient in whom the RIHBD/D1 route was used because of tumor invasion to the left hepatic lobe. The LIHBD/S route was applied in one (6.3%) patient. Successful biliary cannulation was achieved in all patients eventually. The time from the puncture to the guidewire placement in the DEHBD/D2 route (3.5 min) was shorter than that in other methods (14.0 min) (p = 0.014). Adverse events occurred in one (6.3%) patient with moderate pancreatitis. CONCLUSIONS: The proposed algorithm might be useful for the selection of an appropriate approach route in EUS-RV.

Endoscopic ultrasound-guided gallbladder drainage with a combined internal and external drainage tubes for acute cholecystitis.

BACKGROUND AND AIM: Lumen-apposing metal stent is widely used for endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) nowadays but not approved in many countries and might be unsuitable for elective laparoscopic cholecystectomy (LC) because of its large enterocholecysto fistula. A combination of double pigtail plastic stent (DPPS) and naso-cystic tube (NCT) could overcome these problems. The aim of this study was to estimate the efficacy and safety of this method in patients with acute cholecystitis unfit for urgent cholecystectomy both as bridge to surgery and palliation. METHODS: This was a prospective, single-center feasibility study. EUS-GBD was performed with a 7Fr DPPS followed by an NCT placement. NCT was removed after 1 week. LC was performed 2 or 3 months after EUS-GBD in eligible patients. In patients who did not underwent cholecystectomy, DPPS was left in place. RESULTS: Twenty-three patients were enrolled. Both technical and clinical success rates were 96% (22/23). Early adverse events rate was 13% (3/23), including one bile peritonitis, one intraperitoneal abscess, and one melena. LC was attempted in 12 patients, and conversion to open cholecystectomy was required in three (25%). Neither recurrence of cholecystitis nor late adverse event occurred during 6 months of follow up in 10 patients who did not undergo cholecystectomy. CONCLUSION: EUS-GBD with a combination of DPPS and NCT is considered an effective and safe technique both as bridge to surgery and palliation.

Retrospective Comparative Study of Side-by-Side and Stent-in-Stent Metal Stent Placement for Hilar Malignant Biliary Obstruction.

BACKGROUND: In patients with unresectable hilar malignant biliary obstruction (MBO), bilateral metal stent placement is recommended. However, treatment selection between partially stent-in-stent (SIS) and side-by-side (SBS) methods is still controversial. STUDY: Clinical outcomes of bilateral metal stent placement by SBS and SIS methods for hilar MBO were retrospectively studied in four Japanese centers. While large-cell-type uncovered metal stents were placed above the papilla in SIS, braided-type uncovered metal stents were placed across the papilla in SBS. RESULTS: A total of 64 patients with hilar MBO (40 SIS and 24 SBS) were included in the analysis. Technical success rate was 100% in SIS and 96% in SBS. Functional success rate was 93% in SIS and 96% in SBS. Early adverse event rates were higher in SBS (46%) than in SIS (23%), though not statistically significant (P = 0.09). Post-procedure pancreatitis was exclusively observed in SBS group (29%). Recurrent biliary obstruction rates were 48% and 43%, and the median time to recurrent biliary obstruction was 169 and 205 days in SIS and SBS, respectively. CONCLUSIONS: Other than a trend to higher adverse event rates including post-procedure pancreatitis in SBS, clinical outcomes of SIS and SBS methods were comparable in patients with unresectable hilar MBO.

Prospective multicenter study of primary EUS-guided choledochoduodenostomy using a covered metal stent.

BACKGROUND AND OBJECTIVES: EUS-guided biliary drainage (EUS-BD) is increasingly reported as a salvage technique after failed endoscopic retrograde cholangiopancreatography, but it is still controversial whether EUS-BD can replace transpapillary biliary stenting. Therefore, we conducted this multicenter, prospective study of EUS-guided choledochoduodenostomy (EUS-CDS) using a covered metallic stent (CMS) as primary biliary drainage for unresectable distal malignant biliary obstruction (MBO). METHODS: Patients with unresectable distal MBO without any prior drainage are enrolled. Primary endpoint is a technical success and secondary endpoints are adverse events, functional success, and recurrent biliary obstruction (RBO) of EUS-CDS. Clinical outcomes were compared between EUS-CDS and transpapillary stenting as a control. RESULTS: A total of 34 patients were enrolled in 10 Japanese institutions. The cause of MBO was pancreatic cancer in 28 patients. Median tumor size and common bile duct diameter were 31 and 13 mm, respectively. Technical success rate was 97% with a median procedure time of 25 min and functional success rate was 100%. The rate of RBO was 29% and the causes of RBO were nontumor related: Migration in 18%, sludge/food impaction in 9%, and stent impaction to the duodenal wall in 3%. Other adverse events were abdominal pain in 6% and cholecystitis in 9%. A median cumulative time to RBO was 11.3 months. The rate of RBO and cumulative time to RBO of EUS-CDS were comparable to those of transpapillary stenting (36% and 9.1 months, respectively). CONCLUSION: EUS-CDS using a CMS as primary biliary drainage was technically feasible and its safety appeared comparable to transpapillary stenting.

A phase II trial of gemcitabine, S-1 and LV combination (GSL) therapy in patients with advanced pancreatic cancer.

Purpose Our previous phase I trial suggested feasibility of addition of leucovorin (LV) to S-1 and gemcitabine therapy in advanced pancreatic cancer. The aim of this phase II trial was to assess the efficacy and toxicity of gemcitabine, S-1 and LV (GSL) combination therapy for advanced pancreatic cancer. Methods Chemotherapy-naïve patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Gemcitabine was administered at a dose of 1000 mg/m2 by 30 min infusion on days 1, S-1 40 mg/m2 orally twice daily and LV 25 mg orally twice daily on days 1 to 7 every 2 weeks. Primary end point was progression free survival (PFS). Results A total of 49 patients with advanced pancreatic cancer (19 locally advanced and 30 metastatic) were enrolled. Overall response rate and disease control rate were 32.7% and 87.8%. The median PFS and overall survival (OS) were 10.8 (95% confidence interval [CI], 7.4-13.5) and 20.7 (95% CI 13.0-NA) months with 1-year survival rate of 73.4%. Major Grade 3-4 toxicities were neutropenia (22.4%) and stomatitis (14.3%). No toxicity related death was observed. Conclusions In this single center, phase II trial, gemcitabine, S-1 and LV combination therapy was tolerable and can potentially be a treatment option for advanced pancreatic cancer.