BACKGROUND:Oncological principles favour en bloc R0 excision for curative endoscopic resection. In Barrett's neoplasia, endoscopically curable cancers include T1a and selected early T1b disease. Although endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are established treatments, optimal lesion selection remains debated. OBJECTIVE:To evaluate the oncological impact of two selective resection strategies: (1) prioritising ESD for suspected Barrett's cancers >15 mm and (2) a historical approach reserving ESD mainly for advanced cancers. DESIGN:Multicentre retrospective observational study comparing an ESD-first strategy (period 2, 2017-2024) with a historical selective ESD approach (period 1, 2004-2016). Lesion allocation was based on endoscopic assessment of invasion in both periods. Outcomes included basal R0 resection, curative resection, recurrence and adverse events. RESULTS:A total of 581 resections were performed in 542 patients (median lesion size 20 mm). Cancer was present in 271 cases (178 T1a and 93 T1b). Period 2 had a higher cancer burden (52.3% vs 34.9%) and greater ESD use (77.1% vs 21.2%). Basal R0 resection improved from 69.7% to 91.2% (p<0.001), with the greatest benefit in T1b lesions (33.3% to 81.9%, p<0.001). In T1b cancers, curative resection increased (9.5% to 30.5%, p=0.043) and recurrence decreased (55.6% to 23.6%, p=0.043). ESD achieved higher 2-year cancer-free survival than EMR (87.4% vs 50%, p=0.021). Adverse events were infrequent (2.2%) and similar between techniques. CONCLUSION:Prioritising ESD for Barrett's cancers >15 mm improves basal R0 resection, reduces recurrence and improves short-term survival for T1b disease, supporting routine ESD for all larger Barrett's cancers.

Among patients with pancreatic cancer and biliary obstruction planned for pancreaticoduodenectomy, preoperative biliary drainage (PBD) may be considered during surgical delays. Higher complication rates have been reported for PBD using plastic stents versus early surgery. PBD with a self-expanding metal stent (SEMS) has not been compared with early surgery in a randomized controlled trial (RCT). We conducted a noninferiority RCT comparing PBD using a SEMS versus early surgery at 11 centers in 9 countries. We enrolled patients with resectable pancreatic or periampullary cancer and serum total bilirubin level ≥ 5.8 mg/dL, scheduled for primary resection. Primary endpoint was the proportion of patients reporting ≥ 1 serious adverse event (SAE) 120 days post-randomization. Secondary endpoints included rate of SEMS insertion, rate of curative-intent resection, and all-cause mortality. Among 284 patients, 144 were randomized to PBD and 140 to early surgery. In the modified intention-to-treat primary endpoint analysis, ≥ 1 SAE(s) occurred in 29.0

Background and study aims:Colonoscopy is associated with discomfort that requires intravenous sedation (IVS). The aim of this randomized controlled trial (RCT) was to explore the feasibility of virtual reality distraction (VRD) for colonoscopy using two primary endpoints: cecal intubation rate and the rate of rescue with IVS. Patients and methods:Patients scheduled for elective colonoscopy with IVS were randomized in a 2:1 ratio in favor of VRD, with rescue IVS by propofol if needed. VRD involved use of a device providing a visual and auditive experience similar to clinical hypnosis. Results:Ninety patients were included (VRD:60, IVS: 30). Cecal intubation rate was similar in both groups (92.8% for VRD vs 100% for IVS, P =0.3). The rate of rescue IVS in the VRD group was 63.6%. There was a decrease in median total dose of propofol per patient in the VRD group (1.15 mg/kg for VRD and 4.41 mg/kg for IVS, P <0.001) and in the subgroup of VRD patients who received IVS rescue (3.17 mg/kg for VRD and 4.41 mg/kg for IVS, P =0.003). The median level of pain was higher and the median level of comfort was lower in the VRD group (respectively 3 vs 0, P <0.001 and 7 vs 10, P <0.001). Conclusions:This RCT provides preliminary data to better understand the feasibility of VRD for colonoscopy. We have not identified differences in procedure outcomes compared with conventional IVS, but nevertheless, higher pain and lower comfort scores were reported.

Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Though MASH is closely tied to metabolic risk factors, the underlying pathogenic mechanisms remain scarcely understood. Recent research has emphasized the importance of the gut-liver axis in its pathogenesis, an aspect less explored in human studies. Here, we investigated whether the duodenal epithelium of MASH patients could exhibit intrinsic dysfunctions. Methods: Duodenal epithelial organoids were generated from 16 MASH patients and 14 healthy controls. Biopsies and patient-derived organoid transcriptomes were then analyzed to evaluate if specific intestinal pathways were differentially modulated in MASH subjects. Functional assays were performed to assess the duodenal epithelial absorptive potential and barrier functionality. Results: Organoid formation efficiency was similar between control-derived duodenal epithelial organoids and MASH-derived duodenal epithelial organoids (MDEOs) (71% and 69%, respectively). Despite global heterogeneity in growth patterns, MDEOs frequently exhibited cystic spheroid morphology. MDEOs displayed altered digestive potential associated with reduced mature absorptive cell fate, but they retained their lipid metabolic capacity, possibly mediated by lipid oxidation in stem/progenitor cells. Additionally, MDEOs misexpressed components of tight and adherens junctions and desmosomes compared to controls. However, MDEOs maintained pore and leak pathway integrity, indicating that the duodenal epithelial barrier remained functionally preserved under tested conditions. Conclusion: This study provides evidence that the duodenal epithelium of MASH patients exhibits significant alterations in its nutrition-related and barrier functions. This study sheds light on the intricate dynamics of duodenal epithelial alterations in MASH, highlighting potential therapeutic avenues for restoring intestinal functions.

615 Background: The most frequently invaded surgical margins on pancreatoduodenectomy (PD) specimens of pancreatic ductal adenocarcinoma (PDAC) are vascular margins, especially the superior mesenteric artery (SMA), also called mesopancreatic margin. Considering embryology, it may be hypothesized that PDAC cells tend to infiltrate the retroperitoneum through the contents of mesopancreas, justifying the frequent SMA positive margin. Because the radiological aspect of mesopancreas has been poorly studied, the aim of this original research was to assess the mesopancreatic infiltration on diagnostic imaging, corroborate with the corresponding margin pathology and evaluate the impact on survival in PDAC patients who underwent PD. Methods: From 2015 to 2021, all patients who underwent PD for PDAC with curative intent were reviewed, excluding patients lost to follow-up, who died postoperatively or within the first year for non-oncological reason, and those with unavailable preoperative imaging. Surgical margins of pathological specimens were reassessed. Blinded reviewing of preoperative radiographic images was conducted. According to qualitative assessment, the mesopancreas tissue was defined as normal fat (NF), fat stranding (FS) or solid infiltration (SI). Results: 133 patients were included in the study, including 51 (38%) who received neoadjuvant therapy. The tumor location was into the head or the uncinate process in 54% and 46%, respectively. At diagnosis, PDAC were classified as resectable (51%), borderline resectable (28%) and locally advanced (9%) according to the NCCN classification. FS or SI in the mesopancreas was present in 45 (34%) and 18 (14%) patients, respectively. Tumor size on imaging, tumor location, chronic obstructive pancreatitis, vascular contacts and NCCN resectability status were predictive factors of mesopancreas infiltration (p<0.001). Median overall and disease-free survivals were significantly lower in case of SI compared to NF and FS in the mesopancreas. When comparing patients with mesopancreatic FS at diagnosis who received neoadjuvant therapy (n=20) to those who underwent upfront surgery (n=25), no significant impact was observed in survivals. R0 resection was obtained in 36%; in all patients with R1 resection, a vascular margin was involved. Tumor size at pathology, SMA margin and resection status were factors that were significantly influenced by the radiological infiltration of the mesopancreas. Conclusions: The SI of mesopancreas on diagnostic imaging was associated with a poor prognosis, but not FS, in patients who underwent PD for PDAC. SMA margin and resection status were correlated with the radiological texture of the mesopancreas, which suggests to further explore underlying mechanisms related to tumoral invasion of vascular margin and mesopancreas.

Background: Pancreatic neuroendocrine tumours (pNETs) are a highly heterogeneous group of tumours with widely variable biological behaviour. The incidence of pNETs has risen exponentially over the last three decades, particularly for asymptomatic small pNETs (≤2 cm), due to the widespread use of cross-sectional imaging in clinical practice. Summary: Current consensus guidelines suggest that incidentally discovered pNETs ≤2 cm can be selectively followed due to the overall low risk of malignancy. Nevertheless, the “watch-and-wait” management strategy for small asymptomatic pNETs is still not widely accepted due to the lack of long-term data on the natural history of these small lesions. Additionally, it is clear that a subset of small pNETs may show malignant behaviour. Key Message: Given the non-negligible risk of malignancy even in small pNETs, it is of the utmost importance to identify other preoperative factors, other than size, that may help to stratify the risk of malignant behaviour and guide clinical management. In this article, the Portuguese Pancreatic Club reviews the importance of risk stratification of pNETs and presents an updated perspective on the surveillance strategy for sporadic well-differentiated pNETs.

[This corrects the article DOI: 10.1016/j.jhepr.2019.10.006.].

Background: The most frequently invaded margins on pancreatoduodenectomy specimens for pancreatic ductal adenocarcinoma are vascular margins, particularly the superior mesenteric artery (or mesopancreatic) margin. Due to limited exploration of the radiological aspect of the mesopancreas, the aim of this study was to evaluate mesopancreatic infiltration through imaging of patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy, to correlate these findings with histopathology and evaluate their impact on survival. Methods: Data for all patients who underwent pancreatoduodenectomy for pancreatic ductal adenocarcinoma from 2015 to 2021 were reviewed, including review of surgical margin histopathology and blinded review of preoperative diagnostic imaging. According to qualitative radiological assessment, the mesopancreas was characterized as having normal fat, fat stranding, or solid infiltration. Survival data were analysed using Cox regression. Results: A total of 149 patients were included. At baseline imaging, mesopancreatic fat stranding or solid infiltration was present in 47 patients (31.5%) and 20 patients (13.4%) respectively. Median overall survival and disease-free survival were significantly lower with mesopancreatic solid infiltration (17 and 8 months) compared with normal fat (30 and 14 months) and fat stranding (29 and 16 months) (P = 0.017 and 0.028 respectively). In multivariable analysis, pathological tumour size was an independent prognostic factor for overall survival, and tumour location in the uncinate process and pathological tumour size were independent prognostic factors for disease-free survival. Conclusion: At diagnostic imaging, solid infiltration (but not fat stranding) of the mesopancreas is associated with a poor prognosis for pancreatic ductal adenocarcinoma patients who undergo pancreatoduodenectomy. Pathological tumour size significantly influences the prediction of overall survival, and tumour location in the uncinate process and pathological tumour size significantly influence the prediction of disease-free survival, suggesting further exploration of underlying mechanisms related to retroperitoneal tumoral invasion of vascular margins and the mesopancreas.

BACKGROUND:Achieving competence in endoscopic retrograde cholangiopancreatography (ERCP) requires extensive training. Recognizing the potential of simulator-based education for safe and effective skill development, we aimed to assess whether initial training with the Boškoski-Costamagna ERCP Trainer (BCT) is beneficial compared with conventional training alone (i.e. predictive validity). METHODS:A prospective multicenter randomized trial involving 16 novice ERCP trainees, randomly assigned to intervention or control groups, was performed. Both underwent hands-on training, with the intervention group receiving additional simulation training during the first 3 months. Each trainee was required to complete a minimum of 60 ERCPs in up to 1 year. The TEESAT score evaluated rates of global overall competence (primary outcome), biliary cannulation, and adverse events (AEs; secondary outcomes). Mixed-effect logistic regression models assessed differences in between-group ERCP procedure competence and success. Learning curves were generated cumulatively over the training period. RESULTS:1106 ERCPs (562 simulator group; 544 control group) were included. Although no statistically significant difference in global overall competence was observed between the groups, possibly owing to data heterogeneity, simulation training demonstrated higher success for native biliary cannulation (52% vs. 42%; P<0.001) and faster median (interquartile range) biliary cannulation times (3 [6] vs. 5 [8] minutes; P<0.001). The simulator group also showed faster improvements in overall performance, native biliary cannulation, and sphincterotomy. No statistical difference was found in overall AEs between the groups. CONCLUSION:Early simulation training with the BCT improved technical competence in native biliary cannulation and accelerated overall ERCP learning. This approach has the potential to enhance ERCP training programs.

Background This study evaluated the safety and efficacy of salvage endoscopic submucosal dissection (ESD) for Barrett's neoplasia recurrence after radiofrequency ablation (RFA). Methods Data from patients at 16 centers were collected for a multicenter retrospective study. Patients who underwent at least one RFA treatment for Barrett's esophagus and thereafter underwent further esophageal ESD for neoplasia recurrence were included. Results Data from 56 patients who underwent salvage ESD between April 2014 and November 2022 were collected. Immediate complications included one muscular tear (1.8%) treated with stent (Agree classification: grade IIIa). Two transmural perforations (3.6%; treated with clips) and five muscular tears (8.9%; two treated with clips) had no clinical impact and were not considered as adverse events. Seven patients (12.5%) developed strictures (grade IIIa), which were treated with balloon dilation. Histological analysis showed 36 adenocarcinoma, 17 high grade dysplasia, and 3 low grade dysplasia. En bloc and R0 resection rates were 89.3% and 66.1%, respectively. Resections were curative in 33 patients (58.9%), and noncurative in 22 patients (39.3%), including 11 "local risk" (19.6%) and 11 "high risk" (19.6%) resections. At the end of follow-up with a median time of 14 (0-75) months after salvage ESD, and with further endoscopic treatment if necessary (RFA, argon plasma coagulation, endoscopic mucosal resection, ESD), neoplasia remission ratio was 37/53 (69.8%) and the median remission time was 13 (1-75) months. Conclusion In expert hands, salvage ESD was a safe and effective treatment for recurrence of Barrett's neoplasia after RFA treatment.

BACKGROUND:Extensive esophageal endoscopic submucosal dissections (ESDs) without preventive measures carry a high risk of stricture. Oral steroids and local injection of triamcinolone acetonide have proven to be effective in Asia for the prevention of esophageal stricture. This study aimed to assess the efficacy of a systematic steroid administration protocol for stricture prevention in a Western center. METHODS:A retrospective review was conducted of all esophageal ESDs performed at H.U.B. Erasme Hospital, Brussels between 2016 and 2022. Injection of triamcinolone was performed for mucosal defects between 50% and 89% of the circumference. We added oral corticosteroids for patients with resections of ≥90% of the circumference. The primary outcome was the incidence of symptomatic stenosis at 3 months. Secondary outcomes included the cumulative stricture rate assessed by endoscopy within 6 months of ESD. Potential risk factors of stricture were evaluated with univariate and multivariate analysis. RESULTS:111 patients underwent 130 esophageal ESDs, with 59 patients receiving triamcinolone acetonide local injection and eight receiving local and oral corticosteroids. The primary outcome demonstrated a stricture incidence of 8.4%. The cumulative stricture rate assessed by endoscopy within 6 months of ESD was 10.4%. A mucosal defect of ≥60 mm in length was associated with a 15-fold increased risk of stricture, with circumferential extent also identified as being an independent prognostic factor for stricture. CONCLUSIONS:Our protocol led to a low stricture rate, even after extensive resection. As a single session treatment without systemic side effects, triamcinolone injection could provide benefits as a preventive method after large esophageal resections.