Takashi Kobayashi

Pancreatic ductal adenocarcinoma develops through pancreatic intraepithelial neoplasia, but when epithelial–stromal remodeling emerges before invasion remains unclear. Here we integrate spatial transcriptomics, histological validation and patient-derived organoids to characterize isolated human low- and high-grade precursor lesions from pancreata without coexisting invasive carcinoma. High-grade lesions show 3.4-fold periductal stromal expansion, enrichment of myofibroblastic fibroblast programs and elevated stromal interleukin-6. Epithelial basal-like features emerge focally before invasion and expand further in invasive carcinoma organoids. Spatial ligand–receptor analyses identify candidate growth-factor and inflammatory interactions between epithelial and stromal compartments. Conditioned medium from one high-grade precursor-derived organoid line induces both myofibroblastic and inflammatory programs in pancreatic stellate cells, providing proof-of-principle functional support. These findings identify high-grade pancreatic intraepithelial neoplasia as a biologically active preinvasive epithelial–stromal ecosystem and motivate validation of candidate mediators in larger cohorts and perturbation studies.

Background and study aims Self-expandable metal stents (SEMS) are widely used for malignant hilar biliary obstruction (MHBO), but whether they improve long-term drainage over plastic stents (PS) is uncertain. As chemotherapy prolongs survival, biliary drainage must be sustained across the remaining disease course. We compared failure of intended lifelong biliary drainage (LDF) between PS-based management and SEMS exposure using a causal inference framework. Patients and methods We retrospectively studied 608 consecutive patients who underwent initial endoscopic drainage for unresectable MHBO at 22 Japanese tertiary centers between January 2020 and March 2024. SEMS use was modeled as a time-varying, irreversible exposure. A marginal structural model with stabilized inverse probability of treatment and censoring weights estimated the adjusted odds ratio (OR) for LDF, defined as the point at which drainage could no longer be maintained by any endoscopic, EUS-guided, or percutaneous approach. Results Over a median follow-up of 184 days, 130 patients (21.4%) had LDF and 384 (63.2%) died. SEMS exposure was associated with higher odds of LDF (adjusted OR, 1.87; 95% CI, 1.28–2.73; P = 0.001), consistent across sensitivity analyses (OR range, 1.75–2.53). The association strengthened from 1.79 at 90 days to 2.93 at 450 days. Cumulative costs were higher in an exploratory analysis. Conclusions SEMS exposure was associated with higher odds of LDF and higher costs than PS-based management. These findings are hypothesis-generating, and prospective studies are needed to determine whether routine first-line SEMS use should be reconsidered when biliary drainage is intended to last across the remaining disease course.

Deep learning models detected direct and indirect imaging findings associated with pancreatic cancer (PC) on abdominal CT scans and diagnosed PC with performance comparable to or better than that of physicians, particularly for small PCs.

Extracorporeal shock wave lithotripsy (ESWL) has been established as the first-line treatment for pancreatic stones in non-surgical therapy.[1] More recently, peroral pancreatoscopy (POPS)-guided electrohydraulic lithotripsy (EHL) has been reported as effective for difficult pancreatic stones and may shorten the treatment course.[2] [3] We present a case of impacted pancreatic stones complicated by pancreatic duct leakage and pleural effusion, successfully treated with POPS-guided EHL in a single session. A 68-year-old man with chronic pancreatitis presented with dyspnea and elevated pancreatic enzymes, with a serum amylase level of 1,480 U/L and a serum lipase level of 1,909 U/L. Computed tomography (CT) revealed two stones in the pancreatic body, accompanied by a peripancreatic fluid collection and left pleural effusion ([Fig. 1a and b]). Thoracentesis demonstrated an elevated amylase level in the pleural fluid of 52,060 U/L, consistent with pleural effusion secondary to pancreatic duct leakage. A chest tube was placed, and ERCP was performed for pancreatic duct drainage. Pancreatography revealed two impacted stones in the pancreatic body preventing guidewire advancement into the distal duct ([Fig. 2a]). A POPS (SpyGlass DS; Boston Scientific, Marlborough, MA, USA) was introduced into the main pancreatic duct (MPD), allowing the visualization of the pancreatic stone ([Fig. 2b]). Repeated EHL (AUTOLITH TOUCH; Northgate Technologies Inc., Elgin, IL, USA) achieved fragmentation of both the proximal and distal stones ([Fig. 2c]). This enabled distal MPD opacification and placement of a 5-Fr endoscopic nasopancreatic drainage tube ([Fig. 2d]). Repeat ERCP confirmed the resolution of ductal leakage, and residual stone fragments were extracted with a basket catheter. Follow-up CT demonstrated a marked reduction of the pancreatic stones and resolution of the pleural effusion, allowing chest tube removal and discharge ([Video 1]). Video 1 Pancreatoscopy-guided electrohydraulic lithotripsy (EHL) for impacted pancreatic stones. In this case, POPS-guided EHL was preferred over ESWL because immediate stone fragmentation was required to achieve prompt pancreatic duct drainage and control pancreatic duct leakage–associated pleural effusion. Endoscopy_UCTN_Code_TTT_1AR_2AL Received: 14 April 2026 Accepted after revision: 11 May 2026 Article published online: 03 June 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/). Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany