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Background: Same-session endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) is an attractive policy for patients with distal malignant biliary obstruction (DMBO) requiring fine-needle biopsy (FNB) and biliary drainage. However, scanty and conflicting data exists regarding safety and efficacy when comparing these two procedures performed in same versus separate sessions., Methods: Single-center, retrospective, propensity score-matched study including patients with DMBO who underwent EUS-FNB followed by ERCP during the same or separate sessions. The primary outcome was the safety of the procedure [number of patients experiencing adverse events (AEs), overall AEs, its severity, post-ERCP pancreatitis (PEP)]. Secondary outcomes were successful ERCP, use of advanced cannulation techniques, EUS-FNB adequacy, length of hospital stay, overall procedure time, and time to recurrent biliary obstruction., Results: After propensity matching, 87 patients were allocated to each group. AEs developed in 23 (26.4%) vs. 17 (19.5%) patients in the same and separate sessions group, respectively ( p  = 0.280). The overall number, the severity of AEs, and the rate of PEP were similar in the two groups. Secondary outcome parameters were also comparable in the 2 groups., Conclusions: Same-session EUS-FNB followed by ERCP with biliary drainage is safe and does not impair technical outcomes of tissue adequacy and biliary cannulation.

Pancreatic cystic lesions (PCLs) pose a diagnostic challenge due to their increasing incidence and the limitations of cross-sectional imaging and endoscopic-ultrasound-guided fine-needle aspiration (EUS-FNA). EUS-guided through the needle biopsy (EUS-TTNB) has emerged as a promising tool for improving the accuracy of cyst type determination and neoplastic risk stratification. EUS-TTNB demonstrates superior diagnostic performance over EUS-FNA, providing critical preoperative information that can significantly influence patient management and reduce unnecessary surgeries. However, the procedure has risks, with an overall adverse event rate of approximately 9%. Preventive measures and further prospective studies are essential to optimize its safety and efficacy. This review highlights the potential of EUS-TTNB to enhance the diagnostic and management approaches for patients with PCLs. It examines the current state of EUS-TTNB, including available devices, indications, procedural techniques, specimen handling, diagnostic yield, clinical impact, and associated adverse events.

Background/objectives: Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment., Methods: 312 Patients with diagnosis of AIP between January 1st , 2010 and December 31st , 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid)., Results: One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15-379) μg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 μg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15-340) to 202 (40-387) μg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI., Conclusion: The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants., Methods: Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI)., Results: Of 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function., Conclusions: CFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Type 2 is a rare form of autoimmune pancreatitis (AIP). Despite being considered a benign disease, only few studies with limited sample size and short follow-up have been published on type 2 AIP. The aim of this observational study was to evaluate long-term outcomes, such as the risk of relapse, pancreatic insufficiency and cancer in a large type 2 AIP cohort with long follow-up., Methods: Patients with definitive or probable diagnosis of type 2 AIP by International Consensus Diagnostic Criteria (ICDC) present in our prospectively maintained database since 1995 at 31.12.2021 were identified. All patients were clinically evaluated during the year 2022. Clinical, radiological, serological, and pathological data were evaluated., Results: Eighty-eight out of 420 patients present in the database (21%) were diagnosed with type 2 AIP (mean age 33.5 ± 13.5 years). According to the ICDC, 21 patients (23.8%) had a definitive and 67 (76.2%) a probable diagnosis of type 2 AIP. The mean follow-up was 9.2 ± 7.1 years (range 1-27 years). No differences were observed when comparing patients with definitive and probable type 2 AIP diagnosis. Concomitant IBD was reported in 77 patients (87.5%). The probability of disease relapse was lower in patients treated with steroids versus surgery (at 5 years 13% vs. 33%; p = 0.038) but this difference was not statistically significant at multivariable analysis. The risk of endocrine or severe exocrine insufficiency was low (5% and 25%). Four extra-pancreatic malignancies (5%) were diagnosed, none pancreatic. One patient died in a car accident., Conclusions: Type 2 AIP has benign long-term clinical outcomes. Mortality and cancer rates are low and no specific follow-up is needed after radiological remission., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Introduction: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before., Methods: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195)., Results: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported., Discussion: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time., (Copyright © 2023 by The American College of Gastroenterology.)

A small tumor size may impact the diagnostic performance of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing solid pancreatic lesions (SPLs). We aimed to compare the diagnostic yield of EUS-guided fine-needle aspiration (FNA) and biopsy (FNB) in SPLs with a diameter ≤ 15 mm. Consecutive patients who underwent EUS-TA for SPLs ≤ 15 mm between January 2015 and December 2022 in a tertiary referral center were retrospectively evaluated. The primary endpoint was diagnostic accuracy. The final diagnosis was based on surgical pathology or disease evolution after a minimum follow-up of 6 months. Inadequate samples were all considered false negatives for the study. Secondary outcomes included sample adequacy, factors impacting accuracy, and safety. We included 368 patients (52.4% male; mean age: 60.2 years) who underwent FNA in 72 cases and FNB in 296. The mean size of SPLs was 11.9 ± 2.6 mm. More than three passes were performed in 5.7% and 61.5% of patients in the FNB and FNA groups, respectively ( p < 0.0001). FNB outperformed FNA in terms of diagnostic accuracy (89.8% vs. 79.1%, p = 0.013) and sample adequacy (95.9% vs. 86.1%, p < 0.001). On multivariate analysis, using FNA (OR: 2.10, 95% CI: 1.07-4.48) and a final diagnosis (OR: 3.56, 95% CI: 1.82-6.94) of benign conditions negatively impacted accuracy. Overall, the adverse event rate was 0.8%, including one pancreatitis in the FNA group and one pancreatitis and one bleeding in the FNB group, all mild and conservatively managed. EUS-TA for SPLs ≤ 15 mm has a high diagnostic yield and safety. This study suggests the superiority of FNB over FNA, with better performance even with fewer passes performed., Competing Interests: The authors declare no conflicts of interest.

Introduction: Chronic pancreatitis is a common inflammatory disease that severely impairs patients' quality of life, mainly due to abdominal pain which is the most frequent symptom. Current guidelines suggest medical therapy as the first line intervention based on a stepwise use of analgesics (i.e. NSAIDs followed by weak opioids and later by strong oppioids), which is rarely effective in improving pain and often leads to opioid addiction. Interventional procedures are therefore frequently needed. Endoscopic therapy is suggested as the second line of intervention, aiming at decompressing the main pancreatic duct via structure dilatation and ductal stone removal. Endoscopic therapy is usually effective in reducing pain in the short term, but its effects frequently decrease with time and multiple procedures are often required. Surgery is usually reserved as a last resource when medical and endoscopic therapy have failed. Pancreatic surgery is burdened with non negligible morbidity and mortality but is effective in reducing pain and improving quality of life in chronic pancratitis with long lasting effects., Areas Covered: Surgical treatment of chronic pancreatitis is based on resection of inflammatory head mass or decompression of the ductal system, alone or in combination, which can be performed using different techniques. In this paper we reviewed the current evidence on the long-term outcomes of this type of surgery in terms of pain relief, quality of life, exocrine end endocrine function, and long-term mortality., Expert Opinion: Quality of current evidence on this field is on average poor; a consensus to define clinically significant outcomes is needed in order to correctly design prospective studies that will enable gastroenterologists to understand which patients, and when, will benefit most from surgery and should therefore be referred to surgeons.

Overweight and obesity are some of the most important health challenges. Many diseases are related to these metabolic disorders, and, among them, the pancreatic fat accumulation, also called "pancreatic steatosis" or "nonalcoholic fatty pancreas", seems to have an emerging role in different conditions. There are different method to evaluate the fat content in the pancreas, such as histology, different imaging techniques and endoscopic ultrasound, but there is no gold standard for the correct diagnosis and for the identification of "inter/intralobular" and "intra-acinar" pancreatic fat. However, the fat storage in the pancreas is linked to chronic inflammation and to several conditions, such as acute and chronic pancreatitis, type 2 diabetes mellitus and pancreatic cancer. In addition, pancreatic fat accumulation has also been demonstrated to play a role in surgical outcome after pancreatectomy, in particular for the development of postoperative pancreatic fistula. Different possible therapeutic approaches have been proposed, but there is still a lack of evidence. The aim of this review is to report the current evidence about the relationship between the obesity, the pancreatic fat accumulation and its potential role in pancreatic diseases., (© 2023. The Author(s).)

Background: Endoscopic ultrasound (EUS) is a main tool in pancreatology for both diagnosis and therapy. It allows minimally invasive differentiation of various diseases, with a minimal degree of inflammation or anatomic variations. EUS also enables interventional direct access to the pancreatic parenchyma and the retroperitoneal space, the pancreatic duct, the pancreatic masses, cysts, vascular structures for diagnostic and therapeutic purposes., Summary: This review aimed to summarize the new developments of EUS in the field of pancreatology, with special interest on inflammation and interventions. EUS enables way to perform pseudocyst drainage, necrosectomy, transenteral drainage and transenteric access of the main pancreatic duct, or the direct visualization or therapy of vascular structures adjacent to the pancreas., Key Messages: EUS has a deep impact on pancreatology, and the development of new diagnostic and interventional approaches to the retroperitoneal space and the pancreas has increased in the last years exponentially, allowing minimal invasive diagnostics and therapy and avoiding surgery and percutaneous therapy ., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Cap-assisted endoscopic mucosal resection (EMR-c) has emerged as a potential alternative to standard piecemeal wide-field EMR (WF-EMR) for the resection of laterally spreading tumors (LSTs). However, clear indications for this technique are still lacking. Our objective was to investigate the performance of salvage EMR-c after WF-EMR failure in the resection of large colorectal LSTs., Methods: The data of consecutive patients undergoing WF-EMR for large colorectal LSTs (2015-2021) were analyzed in this single-center, retrospective, observational study. In the event of a WF-EMR failure, the procedure was switched to EMR-c in the same session. The efficacy of the two techniques was evaluated in terms of complete endoscopic resection, R0 resection, and recurrence rate. Safety was also assessed., Results: Overall, the data from 81 WF-EMRs were collected. Eighteen cases of WF-EMR failure were switched to EMR-c in the same session and complete endoscopic resection was achieved in 17/18 patients (94.4%). No statistically significant difference was observed between WF-EMR and salvage EMR-c in terms of macroscopic radicality (P = 0.40) and R0 resection (P = 0.12). However, recurrence was more common with EMR-c (44.4% vs. 23.5%; P = 0.05), as were adverse events, particularly intraprocedural bleeding (27.8% vs. 7.9%; P = 0.04)., Conclusion: EMR-c is an effective salvage technique for challenging colorectal LSTs following WF-EMR failure. Due to the elevated risk of adverse events associated with this procedure, careful patient selection, endoscopic expertise, and close follow-up are strongly recommended., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.

Background: Piecemeal endoscopic mucosal resection (pEMR) is routinely employed for large laterally spreading tumors (LSTs). Recurrence rates following pEMR are still unclear, especially when cap-assisted EMR (EMR-c) is performed. We assessed the recurrence rates and recurrence risk factors post-pEMR for large colorectal LSTs, including both wide-field EMR (WF-EMR) and EMR-c., Methods: This was a single-center, retrospective study of consecutive patients who underwent pEMR for colorectal LSTs ≥20 mm at our institution between 2012 and 2020. Patients had a post-resection follow-up period of at least 3 months. A risk factor analysis was carried out using the Cox regression model., Results: The analysis included 155 pEMR: 51 WF-EMR and 104 EMR-c, with a median lesion size of 30 (range: 20-80) mm and a median endoscopic follow up of 15 (range: 3-76) months. Overall, disease recurrence occurred in 29.0% of cases; there was no significant difference in recurrence rates between WF-EMR and EMR-c. Recurrent lesions were safely managed by endoscopic removal, and at risk analysis lesion size was the only significant risk factor for recurrence (mm; hazard ratio 1.03, 95% confidence interval 1.00-1.06, P=0.02)., Conclusions: Recurrence of large colorectal LSTs after pEMR occurs in 29% of cases. This rate is mainly dependent on lesion size, and the use of a cap during pEMR has no effect on recurrence. Prospective controlled trials are needed to validate these results., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background: Predicting Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) pancreatitis (PEP) risk can be determinant in reducing its incidence and managing patients appropriately, however studies conducted thus far have identified single-risk factors with standard statistical approaches and limited accuracy., Aim: To build and evaluate performances of machine learning (ML) models to predict PEP probability and identify relevant features., Methods: A proof-of-concept study was performed on ML application on an international, multicenter, prospective cohort of ERCP patients. Data were split in training and test set, models used were gradient boosting (GB) and logistic regression (LR). A 10-split random cross-validation (CV) was applied on the training set to optimize parameters to obtain the best mean Area Under Curve (AUC). The model was re-trained on the whole training set with the best parameters and applied on test set. Shapley-Additive-exPlanation (SHAP) approach was applied to break down the model and clarify features impact., Results: One thousand one hundred and fifty patients were included, 6.1% developed PEP. GB model outperformed LR with AUC in CV of 0.7 vs 0.585 (p-value=0.012). GB AUC in test was 0.671. Most relevant features for PEP prediction were: bilirubin, age, body mass index, procedure time, previous sphincterotomy, alcohol units/day, cannulation attempts, gender, gallstones, use of Ringer's solution and periprocedural NSAIDs., Conclusion: In PEP prediction, GB significantly outperformed LR model and identified new clinical features relevant for the risk, most being pre-procedural., Competing Interests: Conflict of interest All authors declare no conflict of interest., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)