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ESGE suggests endoscopic therapy and/or extracorporeal shockwave lithotripsy (ESWL) as the first-line therapy for painful uncomplicated chronic pancreatitis (CP) with an obstructed main pancreatic duct (MPD) in the head/body of the pancreas. The clinical response should be evaluated at 6 - 8 weeks; if it appears unsatisfactory, the patient's case should be discussed again in a multidisciplinary team and surgical options should be considered.Weak recommendation, low quality evidence.ESGE suggests, for the selection of patients for initial or continued endoscopic therapy and/or ESWL, taking into consideration predictive factors associated with a good long-term outcome. These include, at initial work-up, absence of MPD stricture, a short disease duration, non-severe pain, absence or cessation of cigarette smoking and of alcohol intake, and, after initial treatment, complete removal of obstructive pancreatic stones and resolution of pancreatic duct stricture with stenting.Weak recommendation, low quality evidence.ESGE recommends ESWL for the clearance of radiopaque obstructive MPD stones larger than 5 mm located in the head/body of the pancreas and endoscopic retrograde cholangiopancreatography (ERCP) for MPD stones that are radiolucent or smaller than 5 mm. Strong recommendation, moderate quality evidence.ESGE suggests restricting the use of endoscopic therapy after ESWL to patients with no spontaneous clearance of pancreatic stones after adequate fragmentation by ESWL.Weak recommendation, moderate quality evidence.ESGE suggests treating painful dominant MPD strictures with a single 10-Fr plastic stent for one uninterrupted year if symptoms improve after initial successful MPD drainage. The stent should be exchanged if necessary, based on symptoms or signs of stent dysfunction at regular pancreas imaging at least every 6 months. ESGE suggests consideration of surgery or multiple side-by-side plastic stents for symptomatic MPD strictures persisting beyond 1 year after the initial single plastic stenting, following multidisciplinary discussion. Weak recommendation, low quality evidence.ESGE recommends endoscopic drainage over percutaneous or surgical treatment for uncomplicated chronic pancreatitis (CP)-related pseudocysts that are within endoscopic reach.Strong recommendation, moderate quality evidence.ESGE recommends retrieval of transmural plastic stents at least 6 weeks after pancreatic pseudocyst regression if MPD disruption has been excluded, and long-term indwelling of transmural double-pigtail plastic stents in patients with disconnected pancreatic duct syndrome.Strong recommendation, low quality evidence.ESGE suggests the temporary insertion of multiple side-by-side plastic stents or of a fully covered self-expandable metal stent (FCSEMS) for treating CP-related benign biliary strictures.Weak recommendation, moderate quality evidence.ESGE recommends maintaining a registry of patients with biliary stents and recalling them for stent removal or exchange.Strong recommendation, low quality evidence., Competing Interests: G. P. Aithal receives consultancy fees from Shire (September 2015 to present), Pfizer (July 2018 to present), and GSK and Agios (February 2018 to present). A. Anderloni has provided consultancy to Boston Scientific (2017 – 2018). M. J. Bruno has received lecturing and consultancy fees from Boston Scientific, Cook Medical, and Pentax Medical (ongoing) and consultancy fees from Mylan (ongoing); his department is involved in investigator- and industry-initiated studies with Boston Scientific, Cook Medical, and Pentax Medical (ongoing); he is a member (no financial benefit) of the Dutch Pancreatitis Study Group J. Devière receives research support from Olympus for institutional review board-approved studies (ongoing); his department receives research support from Boston Scientific for institutional review board-approved studies (ongoing). J. E. Domínguez-Muñoz has received speaker’s honoraria from Boston Scientific (2018); his department has received financial support for educational activities from Pentax and Boston Scientific (2017 – 2018) and Medtronic (2018). J.-W. Poley receives speaker’s fees and travel expenses from Pentax, Boston Scientific, and Cook Endoscopy (ongoing), and consultancy fees from Boston Scientific and Cook Endoscopy (ongoing). A. Sanchez-Yague has provided paid consultancy to Boston Scientific (2015 – 2018). J. E. van Hooft has received lecture fees from Medtronic (2014 – 2015) and consultancy fees from Boston Scientific (2014 – 2016); her department has received research grants from Cook Medical (2014 – 2018) and Abbott (2014 – 2017). M. Arvanitakis, P. Cantú, M. Delhaye, J.-M. Dumonceau, S. Lekkerkerker, M. Ramchandani, N. Reddy, A. Tringali, and T. Vaysse have no competing interests., (© Georg Thieme Verlag KG Stuttgart · New York.)

1:  ESGE suggests using contrast-enhanced computed tomography (CT) as the first-line imaging modality on admission when indicated and up to the 4th week from onset in the absence of contraindications. Magnetic resonance imaging (MRI) may be used instead of CT in patients with contraindications to contrast-enhanced CT, and after the 4th week from onset when invasive intervention is considered because the contents (liquid vs. solid) of pancreatic collections are better characterized by MRI and evaluation of pancreatic duct integrity is possible. Weak recommendation, low quality evidence. 2:  ESGE recommends against routine percutaneous fine needle aspiration (FNA) of (peri)pancreatic collections. Strong recommendation, moderate quality evidence. FNA should be performed only if there is suspicion of infection and clinical/imaging signs are unclear. Weak recommendation, low quality evidence. 3:  ESGE recommends initial goal-directed intravenous fluid therapy with Ringer's lactate (e. g. 5 - 10 mL/kg/h) at onset. Fluid requirements should be patient-tailored and reassessed at frequent intervals. Strong recommendation, moderate quality evidence. 4:  ESGE recommends against antibiotic or probiotic prophylaxis of infectious complications in acute necrotizing pancreatitis. Strong recommendation, high quality evidence. 5:  ESGE recommends invasive intervention for patients with acute necrotizing pancreatitis and clinically suspected or proven infected necrosis. Strong recommendation, low quality evidence.ESGE suggests that the first intervention for infected necrosis should be delayed for 4 weeks if tolerated by the patient. Weak recommendation, low quality evidence. 6:  ESGE recommends performing endoscopic or percutaneous drainage of (suspected) infected walled-off necrosis as the first interventional method, taking into account the location of the walled-off necrosis and local expertise. Strong recommendation, moderate quality evidence. 7:  ESGE suggests that, in the absence of improvement following endoscopic transmural drainage of walled-off necrosis, endoscopic necrosectomy or minimally invasive surgery (if percutaneous drainage has already been performed) is to be preferred over open surgery as the next therapeutic step, taking into account the location of the walled-off necrosis and local expertise. Weak recommendation, low quality evidence. 8:  ESGE recommends long-term indwelling of transluminal plastic stents in patients with disconnected pancreatic duct syndrome. Strong recommendation, low quality evidence. Lumen-apposing metal stents should be retrieved within 4 weeks to avoid stent-related adverse effects.Strong recommendation, low quality evidence., Competing Interests: J. Albert has received speaker’s honoraria from Fujifilm (2015 – 2016), Falk foundation, and Covidien/Medtronic (2015 – 2017), and both research and speaker’s honoraria from Olympus Europe (2015 – 2017). A. Badaoui received a travel grant from Boston Scientific (2016). M. Barthet is a consultant for and receives research support from Boston Scientific (2016 to present). J. Devière has received research support from Cook Medical (until 2016) and from Boston Scientific (ongoing); his department is receiving research support from Olympus (ongoing). I. Hritz is a consultant (speaker/tutor) for Olympus Europe (ongoing). I. Papanikolaou is co-editor for social media with the Endoscopy journal. J.-W. Poley has received consultancy, travel, and speaker’s fees from Cook Endoscopy and Boston Scientific (ongoing). S. Seewald has received consultancy fees from Boston Scientific (until 2016), and from Olympus and Cook Medical (ongoing). J. van Hooft received lecture fees from Medtronics (2014 – 2015) and a consultancy fee from Boston Scientific (2014 – 2016); her department received research grants from Cook Medical and Abbott (2014 – 2017). K. van Lienden is receiving consultancy and speaker’s fees from Cook Medical (ongoing). M. Arvanitakis, M. A. Bali, M. Besselink, M. Delhaye, J.-M. Dumonceau, A. Ferreira, T. Gyökeres, T. Hucl, M. Milashka, H. van Santvoort, G. Vanbiervliet, and R. Voermans have no competing interests., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background & Aims: Algorithms for diagnosis of malignant common bile duct (CBD) stenoses are complex and lack accuracy. Malignant tumors secrete large numbers of extracellular vesicles (EVs) into surrounding fluids; EVs might therefore serve as biomarkers for diagnosis. We investigated whether concentrations of EVs in bile could discriminate malignant from nonmalignant CBD stenoses., Methods: We collected bile and blood samples from 50 patients undergoing therapeutic endoscopic retrograde cholangiopancreatography at university hospitals in Europe for CBD stenosis of malignant (pancreatic cancer, n = 20 or cholangiocarcinoma, n = 5) or nonmalignant (chronic pancreatitis [CP], n = 15) origin. Ten patients with CBD obstruction due to biliary stones were included as controls. EV concentrations in samples were determined by nanoparticle tracking analyses. The discovery cohort comprised the first 10 patients with a diagnosis of pancreatic cancer, based on tissue analysis, and 10 consecutive controls. Using samples from these subjects, we identified a threshold concentration of bile EVs that could best discriminate between patients with pancreatic cancer from controls. We verified the diagnostic performance of bile EV concentration by analyzing samples from the 30 consecutive patients with a diagnosis of malignant (pancreatic cancer or cholangiocarcinoma, n = 15) or nonmalignant (CP, n = 15) CBD stenosis. Samples were compared using the Mann-Whitney test and nonparametric Spearman correlation analysis. Receiver operating characteristic area under the curve was used to determine diagnostic accuracy., Results: In both cohorts, the median concentration of EVs was significantly higher in bile samples from patients with malignant CBD stenoses than controls or nonmalignant CBD stenoses (2.41 × 10 15 vs 1.60 × 10 14 nanoparticles/L in the discovery cohort; P < .0001 and 4.00 × 10 15 vs 1.26 × 10 14 nanoparticles/L in the verification cohort; P < .0001). A threshold of 9.46 × 10 14 nanoparticles/L in bile best distinguished patients with malignant CBD from controls in the discovery cohort. In the verification cohort, this threshold discriminated malignant from nonmalignant CBD stenoses with 100% accuracy. Serum concentration of EVs distinguished patients with malignant vs patients with nonmalignant CBD stenoses with 63.3% diagnostic accuracy., Conclusions: Concentration of EVs in bile samples discriminates between patients with malignant vs nonmalignant CBD stenosis with 100% accuracy. Further studies are needed to confirm these findings. Clinical Trial registration no: ISRCTN66835592., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality., Design: Retrospective multinational study including SCN diagnosed between 1990 and 2014., Results: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1)., Conclusions: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN., Trial Registration Number: IRB 00006477., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background and Aims: Clarification of the position of the European Society of Gastrointestinal Endoscopy (ESGE) regarding the interventional options available for treating patients with chronic pancreatitis., Methods: Systematic literature search to answer explicit key questions with levels of evidence serving to determine recommendation grades. The ESGE funded development of the Guideline., Summary of Selected Recommendations: For treating painful uncomplicated chronic pancreatitis, the ESGE recommends extracorporeal shockwave lithotripsy/endoscopic retrograde cholangiopancreatography as the first-line interventional option. The clinical response should be evaluated at 6 - 8 weeks; if it appears unsatisfactory, the patient's case should be discussed again in a multidisciplinary team. Surgical options should be considered, in particular in patients with a predicted poor outcome following endoscopic therapy (Recommendation grade B). For treating chronic pancreatitis associated with radiopaque stones ≥ 5 mm that obstruct the main pancreatic duct, the ESGE recommends extracorporeal shockwave lithotripsy as a first step, combined or not with endoscopic extraction of stone fragments depending on the expertise of the center (Recommendation grade B). For treating chronic pancreatitis associated with a dominant stricture of the main pancreatic duct, the ESGE recommends inserting a single 10-Fr plastic stent, with stent exchange planned within 1 year (Recommendation grade C). In patients with ductal strictures persisting after 12 months of single plastic stenting, the ESGE recommends that available options (e. g., endoscopic placement of multiple pancreatic stents, surgery) be discussed in a multidisciplinary team (Recommendation grade D).For treating uncomplicated chronic pancreatic pseudocysts that are within endoscopic reach, the ESGE recommends endoscopic drainage as a first-line therapy (Recommendation grade A).For treating chronic pancreatitis-related biliary strictures, the choice between endoscopic and surgical therapy should rely on local expertise, patient co-morbidities and expected patient compliance with repeat endoscopic procedures (Recommendation grade D). If endoscopy is elected, the ESGE recommends temporary placement of multiple, side-by-side, plastic biliary stents (Recommendation grade A)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background & Aims: Hereditary pancreatitis is an autosomal dominant disease that is mostly caused by cationic trypsinogen (PRSS1) gene mutations. The aim was to determine phenotype-genotype correlations of families in Europe., Methods: Analysis of data obtained by the European Registry of Hereditary Pancreatitis and Pancreatic Cancer was undertaken using multilevel proportional hazards modelling., Results: There were 112 families in 14 countries (418 affected individuals): 58 (52%) families carried the R122H, 24 (21%) the N29I, and 5 (4%) the A16V mutation, 2 had rare mutations, and 21 (19%) had no PRSS1 mutation. The median (95% confidence interval [CI]) time to first symptoms for R122H was 10 (8, 12) years of age, 14 (11, 18) years for N29I, and 14.5 (10, 21) years for mutation negative patients (P = 0.032). The cumulative risk (95% CI) at 50 years of age for exocrine failure was 37.2% (28.5%, 45.8%), 47.6% (37.1%, 58.1%) for endocrine failure, and 17.5% (12.2%, 22.7%) for pancreatic resection for pain. Time to resection was significantly reduced for females (P < 0.001) and those with the N29I mutation (P = 0.014). The cumulative risk (95% CI) of pancreatic cancer was 44.0% (8.0%, 80.0%) at 70 years from symptom onset with a standardized incidence ratio of 67% (50%, 82%)., Conclusions: Symptoms in hereditary pancreatitis start in younger patients and endpoints take longer to be reached compared with other forms of chronic pancreatitis but the cumulative levels of exocrine and endocrine failure are much higher. There is an increasingly high risk of pancreatic cancer after the age of 50 years unrelated to the genotype.