Abstract Background Pancreatic cancer is one of the most lethal malignancies; patients with resectable (R) or borderline resectable (BR) disease are treated with neoadjuvant chemotherapy (NAC) followed by surgery. In those with distal biliary obstruction, preoperative biliary drainage enables the timely initiation and completion of NAC followed by surgery. The optimal stent type remains undetermined; 10-mm covered self-expandable metal stents (CSEMS) provide long patency but increase the risk of cholecystitis and pancreatitis, whereas plastic stents (PS) are safer but have shorter patency. A 6-mm CSEMS potentially offers a balanced option that reduces adverse events while maintaining patency during the preoperative period. The STARDOM trial is designed to determine whether 6-mm CSEMS can maintain stent patency while reducing adverse events in preoperative biliary drainage for R/BR pancreatic cancer with distal biliary obstruction. Methods In a multicenter, open-label, three-arm superiority randomized controlled trial at 89 institutions across Japan, including academic hospitals and high-volume referral centers, 330 adult patients (≥ 18 years) with R/BR pancreatic cancer and distal biliary obstruction requiring preoperative biliary drainage will be recruited by investigators at each participating institution and randomly assigned (1:1:1) to receive either a 10-mm CSEMS, PS (7Fr or 8.5Fr), or 6-mm CSEMS. Patients with severe acute cholangitis or gastrointestinal obstruction will be excluded. Randomization will be stratified by institution, resectability status, and history of cholecystectomy. The primary endpoint is the event-free survival proportion at 12 weeks, defined as the absence of stent-related events including recurrent biliary obstruction (RBO), pancreatitis, cholecystitis, non-occlusive cholangitis, gastrointestinal bleeding, aspiration pneumonia, liver abscess, perforation, or death. Secondary endpoints include the event incidence rate at 12 weeks, event-free survival proportion, and event incidence rate at 12 and 24 weeks in R and BR patients, respectively; the proportion and incidence rate of each primary endpoint component; technical and clinical success; re-intervention success; and surgical outcomes such as surgical resection proportion, operative time, blood loss, postoperative complications, hospital stay, R0 resection proportion, vascular invasion, and lymph node metastasis. Discussion The STARDOM trial is a nationwide multicenter randomized controlled study to directly compare 6-mm CSEMS with conventional 10-mm CSEMS and PS in the pancreatic cancer preoperative setting. Clarifying the optimal drainage method potentially improves perioperative safety, ensures uninterrupted NAC, and supports better oncosurgical outcomes in patients with R/BR pancreatic cancer. Trial registration Japan Registry of Clinical Trials (jRCT ID: jRCT1042250093; registered on August 9, 2025). Trial registry URL: https://jrct.mhlw.go.jp/latest-detail/jRCT1042250093 . First planned enrollment: August 25, 2025.

BACKGROUND:Real-world treatment trajectories and predictors of transition to best supportive care (BSC) in unresectable pancreatic cancer (UPC) remain underexplored. METHODS:This single-center retrospective study (2014-2025) included 274 patients. Overall survival (OS) and time-to-BSC were evaluated using Kaplan-Meier methods and a complete-case multivariable Cox model. Proportional hazards were assessed using Schoenfeld residuals, and treatment-line exposure using a 90-day landmark analysis. RESULTS:Among 274 patients, 248 (90.5%) initiated chemotherapy; 61.3% and 21.8% received ≥2 and ≥3 lines, respectively. Median OS was 9.7 months and increased across treatment-line categories (p < 0.001), and 84.7% transitioned to BSC. Higher C-reactive protein-to-albumin ratio (CAR) was associated with shorter BSC-free survival (p < 0.001). Although baseline CAR did not differ significantly between the chemotherapy and upfront-BSC groups (p = 0.076), it was independently associated with worse OS (HR 2.75), together with ECOG performance status ≥2 (HR 2.64) and liver metastasis (HR 1.62), and its association with mortality attenuated over time. In the 90-day landmark cohort (n = 215), receipt of ≥2 lines by day 90 was associated with longer subsequent OS (13.0 vs. 8.3 months, p = 0.012). CONCLUSIONS:Real-world treatment trajectories in UPC involved frequent transitions to BSC across successive therapy lines. Baseline CAR was independently associated with worse OS and earlier BSC transition and may provide prognostic information beyond performance status. CAR should not be used alone for treatment decisions but may identify patients at risk of early deterioration and prompt timely goals-of-care discussions. Prospective validation, including serial assessment, is warranted.

BACKGROUND & AIMS:The optimal timing for direct endoscopic necrosectomy (DEN) after endoscopic ultrasound (EUS)-guided transmural drainage of symptomatic necrotizing pancreatitis remains unknown. We hypothesized that immediate DEN after EUS-guided drainage might reduce the time to disease resolution compared with a drainage-oriented step-up approach. METHODS:This study was a multicenter, open-label, superiority randomized trial (WONDER-01). Among patients who received EUS-guided treatment for symptomatic necrotizing pancreatitis, eligible patients were randomly assigned 1:1 to receive either immediate DEN or the drainage-oriented step-up approach. The primary endpoint was the time from randomization to clinical success, defined as a decrease in collection size to ≤3 cm and an improvement in inflammatory markers. RESULTS:Seventy patients were enrolled in this study: 33 in the immediate DEN arm and 37 in the step-up arm. Immediate DEN was associated with a shorter time to clinical success than the step-up approach (P = .009), with median times (95% confidence interval) of 29 (19-34) and 44 (38-52) days, respectively. All patients in the immediate DEN arm received DEN compared with 46% in the step-up approach arm, but the rates of procedure-related adverse events were comparable (24% vs 22%, respectively; P = .79). No significant differences were noted between the treatment arms in terms of technical success (100% vs 97%; P > .99) and mortality (12% vs 5.4%; P = .41). CONCLUSIONS:Compared with the step-up approach, immediate DEN after EUS-guided drainage of necrotizing pancreatitis reduced time to clinical success without increasing adverse outcomes but required more DEN procedures (ClinicalTrials.gov, NCT05451901).

Although acute pancreatitis often resolves, its long-term impact on health-related quality of life (HRQoL) and social participation remains unclear. This study investigated the longitudinal changes in HRQoL and factors affecting incomplete recovery of social participation following acute pancreatitis. This multi-center, prospective cohort study included patients aged ≥ 18 years who were hospitalized with acute pancreatitis at 20 hospitals across Japan between April 2018 and March 2024. Patients were consecutively enrolled, and health-related quality of life (HRQoL) was assessed at baseline, 3 months, and 12 months. We evaluated the severity of acute pancreatitis, demographic factors, and HRQoL parameters, including the physical component score (PCS) from the 12-item Short-Form Health Survey version 2 and self-rated health (SRH), as well as social participation status. Among 284 enrolled patients, 226 were included in the primary endpoint analysis. At 3 months, 49 patients (21.7

BACKGROUND:Monitoring data for anamorelin in pancreatic cancer are limited. OBJECTIVE:To descriptively examine week-three documentation-derived dietary intake category, observed body weight, laboratory-derived prognostic nutritional index (PNI), and treatment continuation after anamorelin initiation. METHODS:We retrospectively included week-three-evaluable patients with unresectable or recurrent pancreatic cancer who initiated anamorelin at a Japanese hospital (July 2021-October 2024). Dietary intake category was derived from routine documentation. Paired changes used the Wilcoxon signed-rank test. RESULTS:Among patients (N = 40; PNI, n = 39), dietary intake was classified as increased in 17, stable in 21, and decreased in 2. Median observed body weight was higher at week three than baseline (51.1 vs. 50.2 kg; p = 0.026), whereas median PNI was lower (38.5 vs. 39.8; p = 0.006). The median time-to-discontinuation was 60 days; 16 patients (40.0%) continued ≥84 days. CONCLUSION:These descriptive findings require cautious multidimensional interpretation; causal treatment effects cannot be inferred.

Malignant hilar biliary obstruction (MHBO) remains challenging for biliary decompression. Although endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as an alternative to endoscopic retrograde cholangiopancreatography-guided BD (ERCP-BD), evidence regarding EUS-BD for MHBO is limited. Aims:To evaluate the efficacy and safety of EUS-BD for MHBO. Methods:This multicenter retrospective cohort study included patients with MHBO who underwent EUS-BD at 12 tertiary referral centers between 2012 and 2023. Technical success, clinical success, and procedure-related adverse events (AEs) were assessed. Multivariable analysis was performed to identify factors associated with clinical failure. Results:A total of 141 patients were included. EUS-BD was performed as primary drainage in 67 patients (47.5%) and as rescue drainage after prior ERCP-BD in 74 patients (52.5%); in rescue cases, the reported configurations represented only the EUS-BD component. The overall technical success rate was 98.5% (139/141). Clinical success was achieved in 87.1% (121/139). Among patients who achieved clinical success, the median time to recurrent biliary obstruction was 201 days. Procedure-related AE occurred in 15 patients (10.6%). Multivariable analysis identified Bismuth type IV strictures (odds ratio [OR], 5.89; 95% confidence interval [95% CI], 1.72-24.3) and EUS-BD drainage limited to one or two liver segments (OR, 5.11; 95% CI, 1.49-21.2) as factors associated with clinical failure. Conclusions:EUS-BD is a highly feasible and relatively safe option for BD of MHBO in both primary and rescue settings. Bismuth type IV strictures and EUS-BD drainage limited to one or two liver segments were associated with clinical failure. Trial Registration:N/A.

Evidence for third-line systemic therapy in advanced pancreatic cancer is limited, and observational comparisons risk time-related and selection biases. We evaluated third-line initiation after second-line discontinuation using a 30-day landmark strategy, focusing on treatment timing and patient selection. This single-center retrospective cohort included patients with advanced pancreatic cancer discontinuing second-line systemic therapy between October 2014 and October 2025. The primary analysis included ECOG performance status (ECOG PS) 0–1 patients alive and under observation at day 30. Exposure was initiation within 30 days versus no initiation by day 30, with overall survival (OS) measured from the landmark. Complementary analyses included a 45-day landmark, overlap weighting, time-dependent Cox models, and 60-day mortality after initiation. Among 130 patients, 53 received third-line therapy. The primary 30-day landmark cohort included 48 patients. Early initiation showed a directionally favorable but imprecise association with OS (aHR 0.40, 95

Background Endoscopic retrograde cholangiopancreatography (ERCP), a procedure to treat pancreaticobiliary disorders, is generally safe. However, adverse events (AEs) of post-ERCP pancreatitis (PEP) can occur, which can be fatal. Physicians performing ERCP can take measures to prevent PEP, including endoscopic pancreatic duct stents and pharmacological prophylaxis. Periprocedural aggressive hydration has been investigated for its potential for reducing PEP risk. This study aims to evaluate the efficacy and safety of periprocedural aggressive hydration plus intrarectal diclofenac versus standard hydration therapy plus intrarectal diclofenac in preventing PEP onset in Japanese patients. Methods This phase 3, multicenter, open-label, randomized controlled study is being conducted at an anticipated 27 sites in Japan. The study plans to enroll 780 adults (aged ≥ 18 years) who are scheduled to receive an ERCP procedure. Patients will be randomized 1:1 to the aggressive hydration or standard hydration group. Approximately 8 h prior to the ERCP procedure, patients in both groups will be administered the main infusion (≤ 1.5 mL/kg/h). The aggressive hydration group will receive a bolus of 500 mL Ringer’s solution at the start of the ERCP procedure (500 mL/h) followed by Ringer’s solution administered at 3mL/kg/h for 8 h. The standard hydration group will be administered Ringer’s solution at 1.5 mL/kg/h initiated at the start of the ERCP procedure and continuing for 9 h. Within 30 min of completing the ERCP procedure, patients in both groups will receive intrarectal diclofenac sodium (standard, 50 mg; patients weighing < 50 kg or aged ≥ 80 years, 25 mg). The primary endpoint is the incidence of PEP (serum amylase ≥ 400 U/I after ERCP completion and persistent abdominal pain for ≥ 24 h). Secondary endpoints include the incidence of PEP by severity, the incidence of hyperamylasemia (increase in amylase ≥ 400 U/I), and the incidence of infusion-related AEs. AEs will be monitored throughout the study. Discussion This study aims to clarify whether aggressive hydration reduces PEP incidence versus standard hydration, and to compare PEP incidence by severity, and the incidence of hyperamylasemia and infusion-related AEs. Safety will be determined in both groups. Trial registration: Japan Registry of Clinical Trials (jRCT: s041230145; registered February 6, 2024; https://jrct.mhlw.go.jp/latest-detail/jRCTs041230145)