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Background & Aims: Benign biliary strictures (BBS) are complications of chronic pancreatitis (CP). Endotherapy using multiple plastic stents (MPS) or a fully covered self-expanding metal stent (FCSEMS) are acceptable treatment options for biliary obstructive symptoms in these patients., Methods: Patients with symptomatic CP-associated BBS enrolled in a multicenter randomized noninferiority trial comparing 12-month treatment with MPS vs FCSEMS. Primary outcome was stricture resolution status at 24 months, defined as absence of restenting and 24-month serum alkaline phosphatase not exceeding twice the level at stenting completion. Secondary outcomes included crossover rate, numbers of endoscopic retrograde cholangiopancreatography (ERCPs) and stents, and stent- or procedure-related serious adverse events., Results: Eighty-four patients were randomized to MPS and 80 to FCSEMS. Baseline technical success was 97.6% for MPS and 98.6% for FCSEMS. Eleven patients crossed over from MPS to FCSEMS, and 10 from FCSEMS to MPS. For MPS vs FCSEMS, respectively, stricture resolution status at 24 months was 77.1% (54/70) vs 75.8% (47/62) (P = .008 for noninferiority intention-to-treat analysis), mean number of ERCPs was 3.9 ± 1.3 vs 2.6 ± 1.3 (P < .001, intention-to-treat), and mean number of stents placed was 7.0 ± 4.4 vs 1.3 ± .6 (P < .001, as-treated). Serious adverse events occurred in 16 (19.0%) MPS and 19 (23.8%) FCSEMS patients (P = .568), including cholangitis/fever/jaundice (9 vs 7 patients respectively), abdominal pain (5 vs 5), cholecystitis (1 vs 3) and post-ERCP pancreatitis (0 vs 2). No stent- or procedure-related deaths occurred., Conclusions: Endotherapy of CP-associated BBS has similar efficacy and safety for 12-month treatment using MPS compared with a single FCSEMS, with FCSEMS requiring fewer ERCPs over 2 years. (ClinicalTrials.gov, Number: NCT01543256.)., (Copyright © 2021. Published by Elsevier Inc.)

The human biliary system, a mucosal barrier tissue connecting the liver and intestine, is an organ often affected by serious inflammatory and malignant diseases. Although these diseases are linked to immunological processes, the biliary system represents an unexplored immunological niche. By combining endoscopy-guided sampling of the biliary tree with a high-dimensional analysis approach, comprehensive mapping of the human biliary immunological landscape in patients with primary sclerosing cholangitis (PSC), a severe biliary inflammatory disease, was conducted. Major differences in immune cell composition in bile ducts compared to blood were revealed. Furthermore, biliary inflammation in patients with PSC was characterized by high presence of neutrophils and T cells as compared to control individuals without PSC. The biliary T cells displayed a CD103 + CD69 + effector memory phenotype, a combined gut and liver homing profile, and produced interleukin-17 (IL-17) and IL-22. Biliary neutrophil infiltration in PSC associated with CXCL8, possibly produced by resident T cells, and CXCL16 was linked to the enrichment of T cells. This study uncovers the immunological niche of human bile ducts, defines a local immune network between neutrophils and biliary-resident T cells in PSC, and provides a resource for future studies of the immune responses in biliary disorders., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: A telemedicine service enabling remote surgical consultation had shown promising results. When the service was to be scaled up, it was unclear how contextual variations among different clinical sites could affect the clinical outcomes and implementation of the service. It is generally recognized that contextual factors and work system complexities affect the implementation and outcomes of telemedicine. However, it is methodologically challenging to account for context in complex health care settings. We conducted a work domain analysis (WDA), an engineering method for modeling and analyzing complex work environments, to investigate and represent contextual influences when a telemedicine service was to be scaled up to multiple hospitals., Objective: We wanted to systematically characterize the implementation contexts at the clinics participating in the scale-up process. Conducting a WDA would allow us to identify, in a systematic manner, the functional constraints that shape clinical work at the implementation sites and set the sites apart. The findings could then be valuable for informed implementation and assessment of the telemedicine service., Methods: We conducted observations and semistructured interviews with a variety of stakeholders. Thematic analysis was guided by concepts derived from the WDA framework. We identified objects, functions, priorities, and values that shape clinical procedures. An iterative "discovery and modeling" approach allowed us to first focus on one clinic and then readjust the scope as our understanding of the work systems deepened., Results: We characterized three sets of constraints (ie, facets) in the domain: the treatment facet, administrative facet (providing resources for procedures), and development facet (training, quality improvement, and research). The constraints included medical equipment affecting treatment options; administrative processes affecting access to staff and facilities; values and priorities affecting assessments during endoscopic retrograde cholangiopancreatography; and resources for conducting the procedure., Conclusions: The surgical work system is embedded in multiple sets of constraints that can be modeled as facets of the system. We found variations between the implementation sites that might interact negatively with the telemedicine service. However, there may be enough motivation and resources to overcome these initial disruptions given that values and priorities are shared across the sites. Contrasting the development facets at different sites highlighted the differences in resources for training and research. In some cases, this could indicate a risk that organizational demands for efficiency and effectiveness might be prioritized over the long-term outcomes provided by the telemedicine service, or a reduced willingness or ability to accept a service that is not yet fully developed or adapted. WDA proved effective in representing and analyzing these complex clinical contexts in the face of technological change. The models serve as examples of how to analyze and represent a complex sociotechnical context during telemedicine design, implementation, and assessment., (©Hedvig Aminoff, Sebastiaan Meijer, Urban Arnelo, Kristina Groth. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.06.2021.)

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a 5 year survival rate as low as 9%. One factor complicating the management of pancreatic cancer is the lack of reliable tools for early diagnosis. While up to 50% of the adult population has been shown to develop precancerous pancreatic cysts, limited and insufficient approaches are currently available to determine whether a cyst is going to progress into pancreatic cancer. Recently, we used metabolomics approaches to identify candidate markers of disease progression in patients diagnosed with intraductal papillary mucinous neoplasms (IPMNs) undergoing pancreatic resection. Here, we enrolled an independent cohort to verify the candidate markers from our previous study with orthogonal quantitative methods in plasma and cyst fluid from serous cystic neoplasm and IPMN (either low- or high-grade dysplasia or pancreatic ductal adenocarcinoma). We thus validated these markers with absolute quantitative methods through the auxilium of stable isotope-labeled internal standards in a new independent cohort. Finally, we identified novel markers of IPMN status and disease progression-including amino acids, carboxylic acids, conjugated bile acids, free and carnitine-conjugated fatty acids, purine oxidation products, and trimethylamine-oxide. We show that the levels of these metabolites of potential bacterial origin correlated with the degree of bacterial enrichment in the cyst, as determined by 16S RNA. Overall, our findings are interesting per se, owing to the validation of previous markers and identification of novel small molecule signatures of IPMN and disease progression. In addition, our findings further fuel the provoking debate as to whether bacterial infections may represent an etiological contributor to the development and severity of the disease in pancreatic cancer, in like fashion to other cancers (e.g., Helicobacter pylori and gastric cancer).

1: ESGE recommends that all duodenal adenomas should be considered for endoscopic resection as progression to invasive carcinoma is highly likely.Strong recommendation, low quality evidence. 2: ESGE recommends performance of a colonoscopy, if that has not yet been done, in cases of duodenal adenoma.Strong recommendation, low quality evidence. 3: ESGE recommends the use of the cap-assisted method when the location of the minor and/or major papilla and their relationship to a duodenal adenoma is not clearly established during forward-viewing endoscopy.Strong recommendation, moderate quality evidence. 4: ESGE recommends the routine use of a side-viewing endoscope when a laterally spreading adenoma with extension to the minor and/or major papilla is suspected.Strong recommendation, low quality evidence. 5: ESGE suggests cold snare polypectomy for small (< 6 mm in size) nonmalignant duodenal adenomas.Weak recommendation, low quality evidence. 6: ESGE recommends endoscopic mucosal resection (EMR) as the first-line endoscopic resection technique for nonmalignant large nonampullary duodenal adenomas.Strong recommendation, moderate quality evidence. 7: ESGE recommends that endoscopic submucosal dissection (ESD) for duodenal adenomas is an effective resection technique only in expert hands.Strong recommendation, low quality evidence. 8: ESGE recommends using techniques that minimize adverse events such as immediate or delayed bleeding or perforation. These may include piecemeal resection, defect closure techniques, noncontact hemostasis, and other emerging techniques, and these should be considered on a case-by-case basis.Strong recommendation, low quality evidence. 9: ESGE recommends endoscopic surveillance 3 months after the index treatment. In cases of no recurrence, a further follow-up endoscopy should be done 1 year later. Thereafter, surveillance intervals should be adapted to the lesion site, en bloc resection status, and initial histological result. Strong recommendation, low quality evidence., Competing Interests: M. Arvanitakis has received lecture fees from Olympus. T. Beyna provides consultancy to and gives lectures for Boston Scientific and Cook Medical (ongoing). J.E. van Hooft’s department has received research grants from Cook Medical (from 2014 to 2019) and Abbott (from 2014 to 2017); she has received lecture fees from Medtronics (from 2014 to 2015, 2019) and Cook Medical (from 2019); and she has received consultancy fees from Boston Scientific (from 2014 to 2017). G. Vanbiervliet has provided consultancy to Boston Scientific and Cook Medical (both from 2019 to present). U. Arnelo, M. Barthet, O. Busch, P. Deprez, A. Larghi, G. Manes, A. Moss, K. Nalankilli, B. Napoleon, M. Nayar, E. Pérez-Cuadrado-Robles, L. Kunovsky, S. Seewald, and M. Strijker, declare that they have no conflicts of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

Objectives: Post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP., Methods: An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed-up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated., Results: A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non-users (P = 0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94-2.99, P = 0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non-statin users (P = 0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49-2.13), P = 0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20 minutes, were risk factors., Conclusions: The use of statins or ASA is not associated with a lower risk or a milder course of PEP., (© 2020 Japan Gastroenterological Endoscopy Society.)

1: ESGE recommends against diagnostic/therapeutic papillectomy when adenoma is not proven.Strong recommendation, low quality evidence. 2: ESGE recommends endoscopic ultrasound and abdominal magnetic resonance cholangiopancreatography (MRCP) for staging of ampullary tumors.Strong recommendation, low quality evidence. 3: ESGE recommends endoscopic papillectomy in patients with ampullary adenoma without intraductal extension, because of good results regarding outcome (technical and clinical success, morbidity, and recurrence).Strong recommendation, moderate quality evidence. 4: ESGE recommends en bloc resection of ampullary adenomas up to 20-30 mm in diameter to achieve R0 resection, for optimizing the complete resection rate, providing optimal histopathology, and reduction of the recurrence rate after endoscopic papillectomy.Strong recommendation, low quality evidence. 5: ESGE suggests considering surgical treatment of ampullary adenomas when endoscopic resection is not feasible for technical reasons (e. g. diverticulum, size > 4 cm), and in the case of intraductal involvement (of > 20 mm). Surveillance thereafter is still mandatory.Weak recommendation, low quality evidence. 6: ESGE recommends direct snare resection without submucosal injection for endoscopic papillectomy.Strong recommendation, moderate quality evidence. 7: ESGE recommends prophylactic pancreatic duct stenting to reduce the risk of pancreatitis after endoscopic papillectomy.Strong recommendation, moderate quality evidence. 8: ESGE recommends long-term monitoring of patients after endoscopic papillectomy or surgical ampullectomy, based on duodenoscopy with biopsies of the scar and of any abnormal area, within the first 3 months, at 6 and 12 months, and thereafter yearly for at least 5 years.Strong recommendation, low quality evidence., Competing Interests: M. Arvanitakis has received lecture fees from Olympus. T. Beyna provides consultancy to and gives lectures for Boston Scientific and Cook Medical (ongoing). J.E. van Hooft’s department has received research grants from Cook Medical (from 2014 to 2019) and Abbott (from 2014 to 2017); she has received lecture fees from Medtronics (from 2014 to 2015, 2019) and Cook Medical (from 2019); she has received consultancy fees from Boston Scientific (from 2014 to 2017). G. Vanbiervliet has provided consultancy to Boston Scientific and Cook Medical (both from 2019 to present). A. Aelvoet, U. Arnelo, M. Barthet, O. Busch, P. Deprez, A. Larghi, G. Manes, A. Moss, B. Napoleon, M. Nayar,E. Pérez-Cuadrado-Robles, L. Kunovsky, S. Seewald, and M. Strijker, declare that they have no conflicts of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

Background: The impact of high-volume care in total pancreatectomy (TP) is barely explored since annual numbers are mostly low. This study evaluated surgical outcomes after TP over time in a high-volume center., Methods: All adult patients (age ≥ 18 years) who underwent an elective single-stage TP at Karolinska University Hospital were retrospectively analysed (2008-2017). High volume was defined as > 20 TPs/year., Results: Overall, 145 patients after TP were included, including 86 (59.3%) extended resections. Major morbidity was 34.5% (50/145) and 90-day mortality 5.5% (8/145). The relative use of TP within all pancreatectomies increased from 5.4% (63/1175) in 2008-2015 to 17.3% (82/473) in 2016-2017 (p < 0.001). Over time, TP was more often performed to achieve radicality (n = 11, 17.5% to n = 31, 37.8%; p = 0.007). In multivariable logistic regression analysis, an annual TP-volume of > 20 was associated with reduced major morbidity (odds ratio [OR] = 0.225, 95% confidence interval [CI], 0.097-0.521; p < 0.001). In the high-volume years (2016-2017), major morbidity (n = 31, 49.2% to n = 19, 23.2%; p = 0.001) and relaparotomy rate (n = 13, 20.6% to n = 5, 6.1%; p = 0.009) improved. Improvements occurred mainly after extended TP, including lower major morbidity (n = 22, 57.9% to n = 12, 25.0%; p = 0.002) and in-hospital mortality (n = 3, 7.9% to n = 0, 0%; p = 0.082)., Conclusions: In a single, high-volume center study, an increase in surgical volume of TP was associated with improved perioperative outcomes, especially for extended resections.

Objective: Neoadjuvant therapy (NAT) has become part of the multimodality treatment for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC)., Summary Background Data: It is currently uncertain which are the preferable NAT regimens, who benefits from surgery, and whether more aggressive surgical strategy is motivated., Methods: A retrospective cohort analysis was performed for all patients with BRPC/LAPC discussed and planned for NAT at multidisciplinary conference at Karolinska University Hospital from 2010 to 2017., Results: Of 233 patients eligible, 168 (72%) received NAT and were reevaluated for possibility of resection. A total of 156 (67%) patients (mean 64 yrs, 53% male) had pancreatic adenocarcinoma, comprising the study group for survival analysis. LAPC was diagnosed in 132 patients (85%), BRPC in 22 (14%), and resectable tumor in 2 (1.3%). Fifty patients (40.3%) received full-dose NAT. Only 54 (34.6%) had FOLFIRINOX. The overall survival among resected patients was similar for BRPC and LAPC (median survival 15.0 vs 14.5 mo, P = 0.4; and 31.9 vs 21.8 mo, P = 0.7, respectively). Resected patients had better survival than nonresected, irrespective of the type or whether full-dose NAT was given (median survival 22.4 vs 12.7 mo; 1-, 3-, and 5-yr survival: 86.4%, 38.9%, 26.9% vs 52.2%, 1.5%, 0%, respectively (P < 0001). For all preoperative values of Ca 19-9, surgical resection had positive impact on survival., Conclusions: All patients with BRPC/LAPC who do not progress during NAT should be considered for surgical resection, irrespective of the type or dose of NAT given. Higher levels of Ca 19-9 should not be considered an absolute contraindication for resection., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Endoscopic sutures can be used in various clinical situations where closure or fixation is needed. Stents that migrate and dislocated probes can be fixated by endoscopic sutures. The sutures can be used to stop gastrointestinal bleeding. It is possible to close perforations, leaks and fistulas with endoscopic sutures, but as with ordinary sutures, the indication must be correct for the procedure to be successful. Endoscopic sleeve gastroplasty (ESG) can be done by a series of sutures reducing the volume of the stomach. Defects after endoscopic resections, where bleeding or perforations can be expected, can be closed with endoscopic sutures. Complications are uncommon but intraabdominal fluid collection may occur after ESG. Endoscopic sutures have the same possibilities and limitations as traditional or laparoscopic sutures. Properly used, the method is safe, but the instruments are still difficult to work with and require an experienced endoscopist who has undergone proper training.

Background: Telemedicine innovations are rarely adopted into routine health care, the reasons for which are not well understood. Teleguidance, a promising service for remote surgical guidance during endoscopic retrograde cholangiopancreatography (ERCP) was due to be scaled up, but there were concerns that user attitudes might influence adoption., Objective: Our objective was to gain a deeper understanding of ERCP practitioners' attitudes toward teleguidance. These findings could inform the implementation process and future evaluations., Methods: We conducted semistructured interviews with ERCP staff about challenges during work and beliefs about teleguidance. Theoretical constructs from the technology acceptance model (TAM) guided the thematic analysis. Our findings became input to a 16-item questionnaire, investigating surgeons' beliefs about teleguidance's contribution to performance and factors that might interact with implementation., Results: Results from 20 interviews with ERCP staff from 5 hospitals were used to adapt a TAM questionnaire, exchanging the standard "Ease of Use" items for "Compatibility and Implementation Climate." In total, 23 ERCP specialists from 15 ERCP clinics responded to the questionnaire: 9 novices (<500 ERCP procedures) and 14 experts (>500 ERCP procedures). The average agreement ratings for usefulness items were 64% (~9/14) among experts and 75% (~7/9) among novices. The average agreement ratings for compatibility items were somewhat lower (experts 64% [~9/14], novices 69% [~6/9]). The averages have been calculated from the sum of several items and therefore, they only approximate the actual values. While 11 of the 14 experts (79%) and 8 of the 9 novices (89%) agreed that teleguidance could improve overall quality and patient safety during ERCP procedures, only 8 of the 14 experts (57%) and 6 of the 9 novices (67%) agreed that teleguidance would not create new patient safety risks. Only 5 of the 14 experts (36%) and 3 of the 9 novices (33%) were convinced that video and image transmission would function well. Similarly, only 6 of the 14 experts (43%) and 6 of the 9 novices (67%) agreed that administration would work smoothly. There were no statistically significant differences between the experts and novices on any of the 16 items (P<.05)., Conclusions: Both novices and experts in ERCP procedures had concerns that teleguidance might disrupt existing work practices. However, novices were generally more positive toward teleguidance than experts, especially with regard to the possibility of developing technical skills and work practices. While newly trained specialists were the main target for teleguidance, the experts were also intended users. As experts are more likely to be key decision makers, their attitudes may have a greater relative impact on adoption. We present suggestions to address these concerns. We conclude that using the TAM as a conceptual framework can support user-centered inquiry into telemedicine design and implementation by connecting qualitative findings to well-known analytical themes., (©Hedvig Aminoff, Sebastiaan Meijer, Urban Arnelo, Susanne Frennert. Originally published in JMIR Formative Research (http://formative.jmir.org), 11.01.2021.)

Emerging research suggests gut microbiome may play a role in pancreatic cancer initiation and progression, but cultivation of the cancer microbiome remains challenging. This pilot study aims to investigate the possibility to cultivate pancreatic microbiome from pancreatic cystic lesions associated with invasive cancer. Intra-operatively acquired pancreatic cyst fluid samples showed culture-positivity mainly in the intraductal papillary mucinous neoplasm (IPMN) group of lesions. MALDI-TOF MS profiling analysis shows Gammaproteobacteria and Bacilli dominate among individual bacteria isolates. Among cultivated bacteria, Gammaproteobacteria, particularly Klebsiella pneumoniae , but also Granulicatella adiacens and Enterococcus faecalis , demonstrate consistent pathogenic properties in pancreatic cell lines tested in ex vivo co-culture models. Pathogenic properties include intracellular survival capability, cell death induction, or causing DNA double-strand breaks in the surviving cells resembling genotoxic effects. This study provides new insights into the role of the pancreatic microbiota in the intriguing link between pancreatic cystic lesions and cancer.

Objective: The purpose of this study is to determine preoperative factors that are predictive of malignancy in patients undergoing pancreatic resection for intraductal papillary mucinous neoplasms (IPMN)., Summary Background Data: IPMN of the pancreas may be precursor lesions to pancreatic cancer (PC) and represent a target for early diagnosis or prevention. While there has been much effort to define preoperative risk factors for malignant pathology, guidelines are ever-changing and controversy remains surrounding which patients would benefit most from resection., Methods: We performed a retrospective analysis of 901 consecutive patients obtained from two tertiary referral centers who underwent pancreatic resection for histologically proven IPMN between 2004 and 2017. Collected data included patient demographic characteristics, preoperative symptoms, radiological findings, and laboratory data., Results: Main pancreatic duct (MPD) dilatation was the only variable that was significantly associated with increased probability of malignancy (defined high-dysplasia or invasion) on both univariate and multivariate analysis. Even middle-range MPD dilatation from 5 mm to 9.9 mm (n = 286) was associated with increased odds of HG-IPMN (OR = 2.74; 95% CI = 1.80-4.16) and invasion (OR = 4.42; 95% CI = 2.55-7.66). MPD dilatation >10 mm (n = 150) had even greater odds of HG-IPMN (OR = 6.57; 95% CI = 3.94-10.98) and invasion (OR = 15.07; 95% CI = 8.21-27.65). A cutoff of 5 to 7 mm MPD diameter was determined to be the best predictor to discriminate between malignant and benign lesions., Conclusions: In agreement with current IPMN management guidelines, we found MPD dilatation, even low levels from 5 mm to 9.9 mm, to be the single best predictor of HG-IPMN or invasion, highlighting the critical role that MPD plays in the selection of surgical candidates.

Background and study aims  The aims of this study was to document the clinical and training relevance of endoscopic retrograde cholangiopancreaticography (ERCP) teleguidance (as a clinical model for applied telemedicine) with health economic modeling methodologies. Methods  Probabilities and consequences of complications after ERCP performed by either a novice-trainee or supported through teleguidance (TM) by an expert formed the basis of the health economic model. Results  The main clinical and economic outcomes originated from the base case scenario representing a low-volume center. In the cohort the patient age was 62 years, 58 % were females, the expert was doing ≥ 250 ERCPs per year and 50 for the novice-trainee. The expert knowledge transferred was set to 50 % and the average complexity grade to 1.98. Given a willingness to pay threshold of 56,180 USD/ quality-adjusted life years (QALY), the probability of cost-effectiveness of TM assistance was 98.9 %. The probability of a QALY gain for patients having an ERCP, to which was added TM, was 91.6 %. Adding TM saved on an average 111.2 USD (95 % CI 959 to 1021 SEK) per patient, and remained cost-effective basically insensitive to the level of willingness to pay. Conclusion  Teleguidance during an ERCP procedure has the potential to be the prefered option in many low- to medium-volume hospitals. The main mechanisms behind these effects are positive impact on several adverse patient outcomes, QALY increase, and decreased costs. TM should be considered for integration into future teaching curriculums in advanced upper gastrointestinal endoscopy., Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Background and study aims  Conventional endoscopic retrograde cholangiopancreatography (ERCP) is hampered by two-dimensional visualization, post-procedural adverse events (AEs), and exposure to ionizing radiation. Bimodal ERCP might mitigate these challenges, but no reports of its use are available to date. The aim of this study was to explore the feasibility of bimodal ERCP, while investigating its potential clinical yield. Patients and methods  This was a retrospective observational study of patients that underwent bimodal ERCP in a single tertiary academic referral center. Thirteen patients undergoing conventional ERCP had a previously T2-weighted isotropic 3 D TSE MRCP sequence aligned and fused with the two-dimensional image generated from the fluoroscopy c-arm unit in real time. Results  Over a 2-month period, 13 patients with a mean age of 54 underwent bimodal ERCP for bile duct stricture (61.5 %), complex cholelithiasis (7.7 %) and ductal leakage (30.1 %). Bimodal ERCP was feasible in all 13 cases, and image quality was assessed as "good" in 11 patients (84.6 %). Bimodal ERCP aided in visualizing the lesion of interest (76.9 %), assisted in understanding the 3 D anatomy of the biliopancreatic ductal system (61.5 %), and aided in finding a favorable position for the c-arm (38.4 %) for subsequent therapeutic intervention. Conclusions  This first report on bimodal ERCP proves its feasibility and suggests that it may assist in increasing both the diagnostic and therapeutic yield of ERCP, while at the same time decreasing AEs during and after ERCP. Its main application might lie in treatment of complex intrahepatic disease., Competing Interests: Competing interests The authors declare that they have no conflict of interest.

Background: Total pancreatectomy (TP) is rarely performed due to concerns for endocrine and exocrine insufficiency and decreased quality of life (QoL). Renewed interest is seen in recent years, but large cohort studies remain scarce. This study was designed to evaluate endocrine and exocrine insufficiency after TP and its impact on QoL., Methods: Adult patients (age ≥ 18 years) who underwent TP between 2008 and 2017 at Karolinska University Hospital with at least 6 months follow-up were included. Endocrine and exocrine insufficiency and QoL were assessed using validated questionnaires (EORTC QLQ-C30, QLQ-PAN26, PAID20, and DTSQs). Both pre- and postoperative questionnaires were available in a subgroup., Results: Of 145 TP, 60 patients were eligible of whom 53 (88.3%) with a median of 21 months (interquartile range [IQR] 13-54) follow-up were included. Symptomatic hypoglycemia occurred in 90.6% (48/53) of patients, and 25% (12/48) experienced ≥ 1 episodes of loss of consciousness. The PAID20 revealed emotional burnout in seven patients (13.2%), whereas a high satisfaction score of diabetes treatment (median 28, IQR 24-32) was measured according to the DTSQs. Overall, 27 patients (50.9%) reported to have steatorrhea during a median of 2 days (IQR 0-4) in the past week. Overall QoL was reduced compared with a general population (66.7% vs. 76.4%; Δ9.7%) but did not differ with preoperative outcomes (n = 39, 66.7%; IQR 41.7-83.3 vs. 66.7%, IQR 50.0-83.3; P = 0.553) according to the EORTC QLQ-C30., Conclusions: Although the impact of endocrine and exocrine insufficiency on QoL after TP seems acceptable, the management of both insufficiencies should be further improved.

Purpose: To evaluate the practical and radiation safety considerations in utilization of 3-D imaging through cone beam computed tomography (CBCT) in endoscopic retrograde cholangiopancreatography (ERCP)., Method: ERCP procedures were performed using an Artis Q interventional suite (Siemens Healthineers), including 42 procedures with CBCT. Some CBCT cases used the standard "DR" exposure protocol and some used the low dose protocol "DR care". Data on x-ray radiation doses were retrospectively collected and to help optimize technical factors surrounding the procedure and compared to radiation exposure data of patients undergoing conventional ERCP., Results: The median dose area product was 24.4 Gycm 2 for one DR volume and 5.07 Gycm 2 for one DR care volume. The median total dose area product was 6.52 Gycm 2 for conventional ERCP, 48.9 Gycm 2 for procedures using DR and 19.7 Gycm 2 when using DR care. Conventional ERCP resulted in a significantly lower radiation dose than procedures using either CBCT protocols (p < 0.001). However, conventional ERCP showed a large number of outliers with higher dose at the level of, or surpassing, CBCT procedures., Conclusions: For less complex procedures with small x-ray doses and short fluoroscopy times conventional 2-D x-ray technique is clinically sufficient and utilizes less radiation dose than CBCT methods, but there is a wide range of doses and extreme outliers have been observed. CBCT can facilitate ERCP in cases with difficult ducal anatomy, possibly reducing procedural time, x-ray exposure time and need for contrast injections. Methods for prediction on high radiation ERCPs are needed to standardize and optimize patient selection for CBCT-ERCP., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aims: Certain appearances of the major duodenal papilla have been claimed to make cannulation more difficult during ERCP. This study uses a validated classification of the endoscopic appearance of the major duodenal papilla to determine if certain types of papilla predispose to difficult cannulation., Methods: Patients with a naïve papilla scheduled for ERCP were included. The papilla was classified into 1 of 4 papilla types before cannulation started. Time to successful bile duct cannulation, attempts, and number of pancreatic duct passages were recorded. Difficult cannulation was defined as after 5 minutes, 5 attempts, or 2 pancreatic guidewire passages., Results: A total of 1401 patients were included from 9 different centers in the Nordic countries. The overall frequency of difficult cannulation was 42% (95% confidence interval [CI], 39%-44%). Type 2 small papilla (52%; 95% CI, 45%-59%) and type 3 protruding or pendulous papilla (48%; 95% CI, 42%-53%) were more frequently difficult to cannulate compared with type 1 regular papilla (36%; 95% CI, 33%-40%; both P < .001). If an inexperienced endoscopist started cannulation, the frequency of failed cannulation increased from 1.9% to 6.3% (P < .0001), even though they were replaced by a senior endoscopist after 5 minutes., Conclusions: The endoscopic appearance of the major duodenal papilla influences bile duct cannulation. Small type 2 and protruding or pendulous type 3 papillae are more frequently difficult to cannulate. In addition, cannulation might even fail more frequently if a beginner starts cannulation. These findings should be taken into consideration when performing studies regarding bile duct cannulation and in training future generations of endoscopists., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Pancreatic cystic neoplasms (PCNs) are a highly prevalent disease of the pancreas. Among PCNs, Intraductal Papillary Mucinous Neoplasms (IPMNs) are common lesions that may progress from low-grade dysplasia (LGD) through high-grade dysplasia (HGD) to invasive cancer. Accurate discrimination of IPMN-associated neoplastic grade is an unmet clinical need. Targeted (semi)quantitative analysis of 100 metabolites and >1000 lipid species were performed on peri-operative pancreatic cyst fluid and pre-operative plasma from IPMN and serous cystic neoplasm (SCN) patients in a pancreas resection cohort (n = 35). Profiles were correlated against histological diagnosis and clinical parameters after correction for confounding factors. Integrated data modeling was used for group classification and selection of the best explanatory molecules. Over 1000 different compounds were identified in plasma and cyst fluid. IPMN profiles showed significant lipid pathway alterations compared to SCN. Integrated data modeling discriminated between IPMN and SCN with 100% accuracy and distinguished IPMN LGD or IPMN HGD and invasive cancer with up to 90.06% accuracy. Free fatty acids, ceramides, and triacylglycerol classes in plasma correlated with circulating levels of CA19-9, albumin and bilirubin. Integrated metabolomic and lipidomic analysis of plasma or cyst fluid can improve discrimination of IPMN from SCN and within PMNs predict the grade of dysplasia.

Chronic pancreatitis is a progressive inflammatory disease of the pancreas potentially giving rise to several complications. For this reason, patients need long-term care and treatment by medical, interventional, and sometimes surgical measures. This article reviews current state-of-the-art strategies and guidelines for treating chronic pancreatitis with conventional and endoscopic measures.

Background: Single-operator, per-oral cholangiopancreatoscopy (SOPCP) enables direct biliopancreatic ductal visualization, targeted tissue sampling, and therapeutic intervention. At Karolinska University Hospital, SOPCP was introduced early and has since been extensively utilized according to a standardized protocol. We analysed the clinical value of SOPCP in the diagnosis and treatment of biliopancreatic diseases in a single high volume center., Methods: All SOPCP procedures performed between March 2007 and December 2014 were retrospectively reviewed. Each procedure's diagnostic yield and therapeutic value was evaluated using a predefined 4 grade scale; 1 - no diagnostic or therapeutic value, 2 - information gained did not impact clinical decision-making and in case of a therapeutic intervention, did not alter the clinical course of the patient, 3 - information gained had an impact on clinical decision-making and in the case of a therapeutic intervention, assisted subsequent disease management, and finally, 4 - information gained was essential and critical for clinical decision-making and in case of a therapeutic intervention, solved the clinical problem requiring no further therapeutic actions. Descriptive statistics were used to analyse results, with uni- and multivariate analyses completed to assess risk of adverse events., Results: During the study period, 365 SOPCP procedures were performed. We found SOPCP of pivotal importance (grade 4) in 19% of cases, and of great clinical significance (grade 3) in 44% of cases. SOPCP did not affect clinical decision-making or alter clinical course (grade 1 and 2) in 37% of cases., Conclusion: SOPCP offers direct access to the biliopancreatic ducts for both diagnostic and therapeutic purposes, adding significant clinical value in 64% of cases., Trial Registration: As this is a purely observational and retrospectively registered study in which the assignment of the medical intervention was not at the discretion of the investigator, it has not been registered in a registry.

Background: Biliary complications occur in 6% to 34% of liver transplant recipients, for which endoscopic retrograde cholangiopancreatography has become widely accepted as the first-line therapy. We evaluated long-term outcome of biliary complications in patients liver transplanted between 2004 and 2014 at Karolinska University Hospital, Stockholm., Methods: Data were retrospectively collected, radiological images were analyzed for type of biliary complication, and graft and patient survivals were calculated., Results: In 110 (18.5%) of 596 transplantations, there were a total of 153 cases of biliary complications: 68 (44.4%) anastomotic strictures, 43 (28.1%) nonanastomotic strictures, 24 (15.7%) bile leaks, 11 (7.2%) cases of stone- and/or sludge-related problems, and 7 (4.6%) cases of mixed biliary complications. Treatment success rates for each complication were 90%, 73%, 100%, 82% and 80%, respectively. When the endoscopic approach was unsatisfactory or failed, percutaneous transhepatic cholangiography or a combination of treatments was often successful (in 18 of 24 cases). No procedure-related mortality was observed. Procedure-related complications were reported in 7.7% of endoscopic retrograde cholangiopancreatography and 3.8% of percutaneous transhepatic cholangiography procedures. Patient survival rates, 1, 3, 5, and 10 years posttransplant in patients with biliary complications were 92.7%, 80%, 74.7%, and 54.1%, respectively, compared with 92%, 86.6%, 83.7%, and 72.8% in patients free from biliary complications ( P < 0.01). Similarly, long-term graft survival was lower in the group experiencing biliary complications ( P < 0.0001)., Conclusions: Endoscopic and percutaneous approaches for treating biliary complications are safe and efficient and should be considered complementing techniques. Despite a high treatment success rate of biliary complications, their occurrence still has a significant negative impact on patient and graft long-term survivals., Competing Interests: The authors declare no funding or conflicts of interests.

Introduction: IPMNs, considered precursor lesions of pancreatic adenocarcinoma (PDAC), might display histological alteration varying from low-grade dysplasia (LGD) to cancer. Nevertheless, the prevalence of PDAC is far below the prevalence of IPMN; therefore, not all of these precursor lesions finally progress to cancer. Preoperative features consistent with and finding at final histology of high-grade dysplasia (HGD) or cancer are currently lacking. The aim of this study is to correlate the presence of preoperative clinical features with the finding of advance lesions at final histology., Methods: This is retrospective cohort analysis of patients who underwent surgery for histologically confirmed IPMNs at Karolinska University Hospital, from 2008 to 2015., Results: MPD 6-9.9 mm and ≥ 10 mm were associated with an increased risk of HGD/cancer (respectively, OR 2.92, CI 1.38-6.20, p = 0.005 and OR 2.65, CI 1.12-6.25, p = 0.02). Preoperative high CA19.9 and jaundice were both associated with a higher risk of HGD/cancer at final histology (respectively, OR 4.15, CI 1.90-9.05, p = 0.0003 and OR 15.36, CI 1.94-121.22, p = 0.009). At sex- and age-adjusted multivariable logistic regression analysis, MPD between 6 and 9.9 mm (OR 2.64, CI 1.15-6.06, p = 0.02), jaundice (OR 12.43, CI 1.44-106.93, p = 0.02), and elevated CA19.9 (OR 3.71, CI 1.63-8.46, p = 0.001) remained associated with the occurrence of HGD/cancer., Discussion: The presence of MPD dilation ≥ 6 mm, jaundice, and elevated CA19.9 in IPMN patients are consistent with the finding for HGD/cancer at final histology, thus representing possible markers of advanced lesions suitable for earlier or preventive curative surgical treatment.

Background: Few studies have investigated the outcome of pancreatectomy associated with artery resection (PAR)., Methods: Retrospective analysis of a cohort of operated borderline or locally advanced pancreatic cancer patients with surgically confirmed arterial involvement. Short and long-term outcome were analyzed and compared in patients who underwent PAR (Group 1) and palliative surgery (Group 2)., Results: Of 73 patients who underwent surgical exploration with intent of resection, 34 underwent PAR (±venous resection) (Group 1) and 39 underwent palliation (Group 2). 23 patients (67.7%) in Group 1 underwent combined artery-vein resection (AVR). Operation time was longer and blood loss higher in group 1 compared to group 2. There were no differences in post-operative mortality (2.9% vs 2.6%, p = 0.9) and post-operative surgical complications (38.2% vs 25.6%, p = 0.2). The 1, 3 and 5 years survival in Group 1 was superior to Group 2 (63.7%, 23.4% and Q3 23.4% vs 41.7%, 3.2% and 0, p = 0.003)., Conclusion: PAR seems to be safe and feasible in well selected patients and associated with an advantage of survival compared to palliation, in patients affected by locally advanced pancreatic cancer., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Detection of early cholangiocarcinoma (CCA) in primary sclerosing cholangitis (PSC) is challenging. The aim of this study was to evaluate the diagnostic accuracy of a stepwise approach to biliary brush cytology with sequential use of fluorescence in-situ hybridization (FISH) for the detection of biliary malignancy in PSC., Method: We retrospectively studied consecutive patients with PSC who underwent biliary brushings at Karolinska University Hospital between 2009 and 2015 (n = 208). Brush samples were categorized as benign, equivocal (atypical or suspicious) and malignant. Equivocal cases were further analysed with FISH. Samples with a malignant cytology or positive FISH were considered positive. The diagnosis was determined after 12 months of follow-up., Results: The diagnosis CCA was confirmed in 15 patients (7%), high-grade dysplasia in three patients, and low-grade dysplasia in five patients at follow-up. Using the diagnostic algorithm, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for a diagnosis of CCA were 80% (95%CI 52%-96%), 96% (95%CI 92%-98%), 60% (95%CI 36%-81%) and 98% (95% CI 95%-100%). In patients with equivocal cytology (n = 61), the sensitivity for CCA diagnosis increased to 100% (95%CI 72%-100%) with a lower PPV of 58% (95%CI 34%-78%). The diagnostic accuracy for detection of CCA in all patients was 95% (95%CI 91%-97%)., Conclusion: Biliary brush cytology with sequential use of FISH in equivocal cases seems to be a highly predictive diagnostic test for CCA in PSC. These results support the use of FISH when cytology is equivocal for detection of biliary malignancy in PSC., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Interventional treatment with stents in pancreatic cancer is a topic that developed during recent years and new fields of palliative stent therapy have evolved. The increasing life expectancy of patients with unresectable pancreatic cancer increases the need for clinical and cost effective therapeutic interventions. Current literature, guidelines, practice and evidence were reviewed. Besides the most obvious biliary stenting via endoscopic retrograde cholangiopancreatography (ERCP), pancreatic and gastroduodenal stenting as well as percutaneous transhepatic cholangiography (PTC) and the rapidly growing field of endosonographic stent implantation in the palliative care of patients with pancreatic cancer are being discussed from several points of view in this review., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background and Aim: The rendezvous postoperative endoscopic retrograde cholangiopancreatography (ERCP) technique has been introduced as a modification of the single-session rendezvous intraoperative ERCP procedure in the management of concurrent common bile duct stones during cholecystectomy. There are no reports on the impact of this modified technique on post-ERCP morbidity. The objective of the present study was to study and compare the rendezvous techniques in terms of procedure-associated morbidities, such as post-ERCP pancreatitis and postoperative infections., Methods: The Swedish National Registry for Gallstone Disease and ERCP was searched for ERCP procedures cross-matched with cholecystectomies for the same patient carried out for gallstone indications between 2008 and 2014. A total of 1770 rendezvous ERCP procedures were retrieved and included in this study. The ERCP procedures were considered rendezvous intraoperative or rendezvous postoperative, depending on whether the ERCP procedure was carried out during or after completing the cholecystectomy., Results: There were 1205 and 565 ERCP procedures in the rendezvous intraoperative and the rendezvous postoperative groups, respectively. The cohorts were similar in age and gender distribution. Overall complication rates were higher in the rendezvous postoperative group compared with the rendezvous intraoperative group (19.7% vs 14%, P = 0.004), involving specifically post-ERCP pancreatitis (6.4% vs 3.2% P = 0.003) and postoperative infections (4.4% vs 2.3% P = 0.028). Despite similar stone clearance rates, there were higher rates of retained stones in the rendezvous postoperative group (5.5% vs 0.6%, P < 0.001)., Conclusions: Single-session rendezvous intraoperative ERCP is superior to the rendezvous postoperative ERCP technique in terms of post-ERCP pancreatitis and postoperative infections., (© 2018 Japan Gastroenterological Endoscopy Society.)

Introduction: In patients with pancreaticobiliary lesions anticipating surgical resection, digital pancreaticocholangioscopy can be used to identify the extent of disease. This presurgical"mapping" could change the surgical plan and optimize patient care., Materials and Methods: Patients with pancreaticobiliary lesions anticipating surgery who underwent endoscopic retrograde cholangiopancreatography with digital pancreaticocholangioscopy from 9 international centers were included. Primary outcome was whether pancreaticocholangioscopy altered the surgical plan. Secondary outcome was correlation between surgical and endoscopic histology and adverse events., Results: A total of 118 patients were included (64% male, mean age 69 y): cholangioscopy in 105 patients (89%), pancreatoscopy in 13 patients (11%). Pancreaticocholangioscopy changed the surgical plan in 39 (34%) of patients: 8 of 13 in the pancreatic duct, 32 of 105 in the bile duct. In the bile duct, 6 patients (5%) had less extensive surgery, 26 patients (25%) avoided surgery. In the pancreatic duct, 4 patients (31%) had more extensive surgery and 4 patients (31%) had less extensive surgery. Four patients with downstaged surgery had positive margins on surgical resection; 1 required additional surgical intervention. Overall correlation between endoscopy and surgical histology was 88%. Adverse events included post endoscopic retrograde cholangiopancreatography pancreatitis in 3 patients (2.5%)., Conclusion: Digital pancreaticocholangioscopy can be effectively used as a mapping tool to delineate the degree of involvement of biliary lesions before surgical resection, in some cases altering the surgical plan. Prospective studies are needed, especially when downstaging surgery.

Introduction: Autoimmune pancreatitis (AIP) is a pancreatic inflammatory process characterized by a strong inflammatory cell infiltration and two histopathologically distinct subtypes: type 1 and type 2. Diagnosis is often challenging and requires a combination of clinical, laboratory and imaging data. AIP can mimic pancreatic tumours leading to unnecessary resections if not correctly diagnosed. Short- and long-term outcomes of AIP have been poorly investigated so far and no large series have been previously reported from Sweden., Methods: A single-centre, retrospective, cohort study of patients with histologically confirmed or highly probable diagnosis of AIP according to ICDC criteria. Demographic, clinical and radiological characteristics, type of treatment and its outcomes were collected and analysed., Results: Seventy-one patients with AIP (87% with type 1), were evaluated at Karolinska University Hospital between 2004 and 2018; 49% males, mean age 49 years (range 44-53). Among them, 28% were histologically confirmed, 35% presented with jaundice, 22% with acute pancreatitis, 39% had non-specific symptoms such as weight loss or abdominal pain, 84% showed other organ involvement (OOI). Radiologically, 76% showed a focal pancreatic enlargement, 27% diffuse enlargement, 27% signs of acute pancreatitis and 10% of chronic pancreatitis. Overall, 58 patients (81%) underwent treatment with different medications: 46 (79%) cortisone, 7 (12%) azathioprine, 5 (8%) other immunosuppressive drugs. Twenty-six (36%) underwent biliary stenting and 12 (16%) were given surgery. In total, 47% of patients developed pancreatic exocrine insufficiency (PEI), of whom 76% had a severe form (faecal elastase-1 < 100 μg/g) and 21% of patients developed diabetes mellitus (pancreatic endocrine insufficiency), of whom 73% required insulin., Conclusions: AIP is a challenging disease for diagnosis and treatment. Cortisone treatment is generally successful and provides clinical remission in the large majority of patients (>90%). In the further course of the disease, a considerable number of patients develop PEI and diabetes. Only one-quarter of patients exhibit on imaging the characteristic "sausage-like" pancreas (diffuse enlargement), approximately three-quarters had a focal mass that could be misdiagnosed as pancreatic malignancy., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Primary sclerosing cholangitis (PSC) is a severe chronic liver disease of the small and large bile ducts. The pathogenesis is unknown but a strong immune cell component has been suggested. Mucosal-associated invariant T (MAIT) cells are abundant in human liver and localize around bile ducts. Yet, the role of MAIT cells in PSC remains unclear. Here, we performed a detailed characterization of MAIT cells in circulation and assessed their presence in bile ducts of PSC patients as well as non-PSC controls. We observed a dramatic reduction in MAIT cell levels in PSC patients. High-dimensional phenotypical analysis using stochastic neighbor embedding revealed the MAIT cells to be activated, a phenotype shared by the investigated disease control groups. In line with the noted phenotypic alterations, MAIT cell function was reduced in response to Escherichia coli and to cytokine stimulation in PSC patients as compared to healthy controls. Using a novel sampling approach of human bile ducts, we found MAIT cells to be specifically enriched within bile ducts. Finally, distinct from the dramatic decline observed in circulation, PSC-patients had retained levels of MAIT cells within bile ducts. Altogether, our results provide a detailed insight into how the human MAIT cell compartment is affected in PSC., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: To date, there still is a lack of specific acute pancreatitis markers and specifically an early marker that can reliably predict disease severity. The inflammatory response in acute pancreatitis is mediated in part through oxidative stress and calcineurin-NFAT (Nuclear Factor of Activated T-cells) signaling, which is inducing its own negative regulator, regulator of calcineurin 1 (RCAN1). Caerulein induction is a commonly used in vivo model of experimental acute pancreatitis. Caerulein induces CN-NFAT signaling, reactive oxygen species and inflammation., Methods: To screen for potential markers of acute pancreatitis, we used the caerulein model of experimental acute pancreatitis (AP) in C57Bl/6 J mice. Pancreata from treated and control mice were used for expression profiling. Promising gene candidates were validated in cell culture experiments using primary murine acinar cells and rat AR42J cells. These candidates were then further tested for their usefulness as biomarkers in mouse and human plasma., Results: We identified a number of novel genes, including Regulator of calcineurin 1 (Rcan1) and Sestrin 2 (Sesn2) and demonstrated that they are induced by oxidative stress, by stimulation with H 2 O 2 and by inhibiting caerulein stimulated expression with the antioxidant N-acetylcysteine. We found Rcan1 protein to be significantly elevated in AP-induced mouse plasma as well as in plasma from AP patients., Conclusion: We demonstrated that Rcan1 is regulated by oxidative stress and identified RCAN1 as a potential diagnostic marker of AP., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Delayed cholecystectomy is associated with increased risk of biliary events. The objectives of the study were to confirm the superiority of index cholecystectomy over delayed operation in mild gallstone pancreatitis., Methods: Patients with mild gallstone pancreatitis were randomized into index-or delayed cholecystectomy (IC vs. DC). IC was performed within 48 h from randomization provided a stable or improved clinical condition. The primary outcome was gallstone-related events. Secondary outcomes were rates of cholecystectomy complications, common bile duct stones (CBDS) detected at cholecystectomy and patient reported quality-of-life and pain., Results: Sixty-six patients were randomized into IC (n = 32) or DC (n = 34) between May 2009 and July 2017. There were significantly higher rates of gallstone-related events in the DC compared with the IC group (nine patients vs. one patient, p = 0.013). No statistically significant differences could be demonstrated in cholecystectomy complications (p = 0.605) and CBDS discovered during cholecystectomy (p = 0.302) between the groups. Pain and emotional well-being measured by SF-36 were improved significantly in the IC group at follow-up., Conclusions: Delayed cholecystectomy in mild gallstone pancreatitis can no longer be recommended since it is associated with an increased risk for recurrent gallstone-related events and impaired patient's reported outcomes., Trial Registration Number: clinicaltrials.gov (ID: NCT02630433)., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Dominant strictures occur in approximately 50% of patients with primary sclerosing cholangitis (PSC). Short-term stents have been reported to produce longer resolution of dominant strictures than single-balloon dilatation. We performed a prospective study to compare the efficacy and safety of balloon dilatation vs short-term stents in patients with non-end-stage PSC., Methods: We performed an open-label trial of patients with PSC undergoing therapeutic endoscopic retrograde cholangiopancreatography (ERCP) at 9 tertiary-care centers in Europe, from July 2011 through April 2016. Patients found to have a dominant stricture during ERCP were randomly assigned to groups that underwent balloon dilatation (n = 31) or stent placement for a maximum of 2 weeks (n = 34); patients were followed for 24 months. The primary outcome was the cumulative recurrence-free patency of the primary dominant strictures., Results: Study recruitment was terminated after a planned interim analysis because of futility and differences in treatment-related serious adverse events (SAEs) between groups. The cumulative recurrence-free rate did not differ significantly between groups (0.34 for the stent group and 0.30 for the balloon dilatation group at 24 months; P = 1.0). Most patients in both groups had reductions in symptoms at 3 months after the procedure. There were 17 treatment-related SAEs: post-ERCP pancreatitis in 9 patients and bacterial cholangitis in 4 patients. SAEs occurred in 15 patients in the stent group (45%) and in only 2 patients in the balloon dilatation group (6.7%) (odds ratio, 11.7; 95% confidence interval, 2.4-57.2; P = .001)., Conclusions: In a multicenter randomized trial of patients with PSC and a dominant stricture, short-term stents were not superior to balloon dilatation and were associated with a significantly higher occurrence of treatment-related SAEs. Balloon dilatation should be the initial treatment of choice for dominant strictures in patients with PSC. This may be particularly relevant to patients with an intact papilla. ClinicalTrials.gov no. NCT01398917., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: There are very few data in the current literature regarding the short- and long-term outcome of surgery for pediatric pancreatic tumors (PPT). No data are available on the impact of pancreatic surgery on the children's growth., Methods: This is a retrospective cohort study on a consecutive series of pediatric/adolescent patients who underwent pediatric surgery at Karolinska University Hospital from January 2005 to July 2017., Results: Overall 14 pancreatic operations were performed in 13 patients. The median age was 11.4 years (range 3-15). Six pancreaticoduodenectomies (42.8%), 5 distal pancreatectomies (35.7%), and 3 enucleations (21.5%) were performed. The final histology revealed a solid pseudopapillary tumor in 9 cases (69.2%), neuroblastoma in 1 (7.7%), ganglioneuroma in 1 (7.7%), pancreatoblastoma in 1 (7.7%), and insulinoma in 1 (7.7%). Overall, 3 patients developed post-operative complications (23%). There was no peri-operative mortality. All patients are alive after a median follow-up time of 80 months. Exocrine insufficiency was detected post-operatively in 4 patients (30.7%) Endocrine insufficiency requiring insulin treatment developed in one patient (7.7%). No significant impact on growth was detected in any of the patients after pancreatic resection., Conclusions: In our series, surgery performed for PPTs seems to be safe and effective. The effect of pancreatic surgery on children's growth does not seem to be significant., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Patients with primary sclerosing cholangitis (PSC) have increased risk of cholangiocarcinoma (CCA). We evaluated pre-transplant work-up in PSC patients, to search for the most effective strategy for the detection of biliary dysplasia or early CCA., Methods: Two hundred and twenty five consecutive PSC patients undergoing liver transplantation (LTx) in Sweden between 1999 and 2013 were studied. Patients with CCA or dysplasia in the explanted liver were compared with those with benign histopathology. Measures of test performance were calculated for patients having brush cytology on one endoscopic retrograde cholangiopancreaticography (ERCP) occasion, for those having repeated examinations with or without cholangioscopy, and for fluorescence in situ hybridization (FISH). Survival after LTx was analyzed., Results: Brush cytology on a single ERCP occasion had moderate sensitivity (57%) and high specificity (94%) for the detection of CCA/high grade dysplasia (HGD) in the explanted liver. The corresponding sensitivity and specificity for FISH were 84% and 90%, respectively. Utilizing repeated ERCP and brush cytology to confirm the initial finding improved sensitivity to 82%. Using single operator cholangioscopy (SOC) for targeted examination at the second ERCP improved sensitivity (100%) and specificity (97%) significantly. Mortality rate in patients with incidentally discovered CCA (n = 16) in the explanted liver was significantly higher than in patients with HGD or benign histopathology (HR 16.0; 95% CI, 5.6-45.4; p < .001)., Conclusions: Repeated brush cytology especially when combined with targeted examination under SOC guidance is superior to single brush examinations. This strategy improves the detection of malignancy in PSC and is of importance for selection of patients for LTx.

Morbid obesity is a lifelong disease, and all patients require complementary follow-up including nutritional surveillance by a multidisciplinary team after bariatric procedures. Pancreatic exocrine insufficiency (PEI) refers to an insufficient secretion of pancreatic enzymes and/or sodium bicarbonate. PEI is a known multifactorial complication after upper gastrointestinal surgery, and might constitute an important clinical problem due to the large number of bariatric surgical procedures in the world. Symptoms of PEI often overlap with sequelae of gastric bypass, making the diagnosis difficult. Steatorrhea, weight loss, maldigestion and malabsorption are pathognomonic for both clinical conditions. Altered anatomy after bypass surgery can make the diagnostic process even more difficult. Fecal elastase-1 (FE1) is a useful diagnostic test. PEI should be considered in all patients after bariatric surgery with prolonged gastrointestinal complaints that are suggestive of maldigestion and/or malabsorption. Appropriate pancreatic enzyme replacement therapy should be part of the treatment algorithm in patients with confirmed PEI or symptoms suggestive of this complication.

Background and Study Aims: Preoperative biliary drainage in patients with periampullary tumors and jaundice has been popularized to improve the quality of life and minimize the risks associated with subsequent radical surgery. The aim of this study was to investigate the possible superiority of self-expandable metal stents (SEMS) over plastic stents, by comparing the amount of bacteria in intraoperatively collected bile and using this variable as a proxy for the efficacy of the respective biliary drainage modalities., Patients and Methods: In this randomized clinical trial, 92 patients with obstructive jaundice were enrolled; 45 were allocated to the plastic stent group and 47 to the SEMS group. The primary outcome was the extent and magnitude of biliary bacterial growth at the time of surgical exploration. Secondary outcomes were: macroscopic grading of inflammation of the stented bile ducts, occurrence of adverse events after stenting, stent dysfunction, recognized surgical complexities, and incidence of postoperative complications., Results:  The patients were well matched regarding clinical and disease-specific characteristics. At surgery, there were no group differences in the bacterial amount and composition of the bile cultures or the perceived difficulty of surgical dissection. During the preoperative biliary drainage period, more instances of stent dysfunction requiring stent replacement were recorded in the plastic stent group (19 % vs. 0 %; P  = 0.03). Postoperative complications in patients who underwent curative surgery were more common in patients with plastic stents (72 % vs. 52 %), among which clinically significant leakage from the pancreatic anastomoses seemed to predominate (12 % vs. 3.7 %); however, none of these differences in postoperative adverse events reached statistical significance., Conclusion:  This randomized clinical study was unable to demonstrate any superiority of SEMS in the efficacy of preoperative bile drainage, as assessed by the amount of bacteria in the intraoperatively collected bile. However, some data in favor of SEMS were observed among the clinical secondary outcomes variables (preoperative stent exchange rates) without increases in local inflammatory reactions.

Background: Many endoscopists acknowledge that the appearance of the papilla of Vater seems to affect biliary cannulation. To assess the association between the macroscopic appearance of the papilla and biliary cannulation and other related clinical issues, a system is needed to define the appearance of the papilla., Objective: The purpose of this study was to validate an endoscopic classification of the papilla of Vater by assessing the interobserver and intraobserver agreements among endoscopist with varying experience., Methods: An endoscopic classification, based on pictures captured from 140 different papillae, containing four types of papillae was proposed. The four types are (a) Type 1: regular papilla, no distinctive features, 'classic appearance'; (b) Type 2: small papilla, often flat, with a diameter ≤ 3 mm (approximately 9 Fr); (c) Type 3: protruding or pendulous papilla, a papilla that is standing out, protruding or bulging into the duodenal lumen or sometimes hanging down, pendulous with the orifice oriented caudally; and (d) Type 4: creased or ridged papilla, where the ductal mucosa seems to extend distally, rather out of the papillary orifice, either on a ridge or in a crease. To assess the level of interobserver agreement, a web-based survey was sent out to 18 endoscopists, containing 50 sets of still images of the papilla, distributed between the four different types. Three months later a follow-up survey, with images from the first survey was sent to the same endoscopists., Results: Interobserver agreement was substantial (κ = 0.62, 95% confidence interval (CI) 0.58-0.65) and were similar for both experts and non-experts. The intraobserver agreement assessed with the second survey was also substantial (κ = 0.66, 95% CI 0.59-0.72)., Conclusion: The proposed endoscopic classification of the papilla of Vater seems to be easy to use, irrespective of the level of experience of the endoscopist. It carries a substantial inter- and intraobserver agreement and now the clinical relevance of the four different papilla types awaits to be determined.

Purpose: While surveillance of the majority of patients with IPMN is considered best practice, consensus regarding the duration of follow-up is lacking. This study assessed the survival rate and risk for progression of IPMN under surveillance., Methods: All patients diagnosed with and surveyed for IPMN between January 2008 and December 2013 were identified and assigned to two groups: patients without indication for surgery (Group 1), and patients whose IPMN required surgery but were inoperable for general reasons (Group 2). Disease progression and survival data were compared between both groups., Results: In total 503 patients were identified, of whom 444 (88.3%) were followed up. Group 1 included 395 patients, and Group 2 had 49. In Group 1, IPMN-specific 1-, 5-, and 10-year survival rates were 100, 100, and 94.2%, respectively. Four patients died of associated or concomitant pancreatic cancer, and 230 patients (58.2%) experienced disease progression. The 1-, 4-, 10-year cumulative risk for progression and for surgery was 11.2, 70.6, 97.5, and 2.9, 26.2, 72.1%, respectively. In Group 2, the 1-, 5-, 10-year IPMN-specific survival rate was 90.7, 74.8, and 74.8%, respectively., Conclusions: This study confirmed the safety of surveillance for patients with IPMN who do not require surgery. However, the risk for disease progression and for surgery increases significantly over time. The study results support International and European guidelines not to discontinue IPMN surveillance and validate the European recommendation to intensify follow-up after 5 years. The fairly good prognosis of patients whose IPMN requires surgery but cannot undergo resection suggests a relatively indolent disease biology.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a technically challenging endoscopic procedure, harboring a wide range of complexities within every single investigation. Classifications of the complexity of ERCP have been presented, but do not include modern endoscopic treatment modalities. In order to be able to target resources and compare the results of different endoscopic centers, a new complexity grading system for ERCP is warranted. This study launches a new complexity grading scale for ERCP-the H.O.U.S.E.-classification., Methods: The medical record of every patient undergoing ERCP 2009-2011 at the Karolinska University Hospital was reviewed, regarding the complexity of the procedure, and categorized into one out of three-grades in the HOUSE classification system, and concomitantly graded according to the Cotton grading system. All ERCP-procedures were also registered in the Swedish registry for gallstone surgery and ERCP (GallRiks) and correlations between the grading systems and procedure related variables as well as outcomes were made., Results: Between 2009 and 2011, 2185 ERCPs were performed at the Karolinska University Hospital, Huddinge. One thousand nine hundred fifty-four of those were index-ERCPs. Another 23 patients were excluded due to lack of postoperative complication registrations, leaving 1931 ERCP procedures to be analyzed. The procedure times were 40 ± 0.7, 65 ± 1.5 and 106 ± 3.2 min, respectively (HOUSE 1-3). The corresponding pancreatitis rates were 3.4, 7.0 and 6.8% and the postoperative complication rates 11.1, 15.7 and 12.8%, respectively., Conclusions: The HOUSE-classification is a novel grading scale for ERCP-complexity. The system can be implemented in clinical practice to allocate resources and allow the comparisons of results between different endoscopic centers. Further studies are warranted to further sharpen this instruments validitity and general clinical relevance.

Background and Objectives: The role of prophylactic pancreatic stenting (PS) in preventing post-endoscopic retrograde cholangio-pancreatography (ERCP) pancreatitis (PEP) has yet to be determined. Most previous studies show beneficial effects in reducing PEP when prophylactic pancreatic stents are used, especially in high-risk ERCP procedures. The present study aimed to address the use of PS in a nationwide register-based study in which the primary outcome was the prophylactic effect of PS in reducing PEP., Methods: All ERCP-procedures registered in the nationwide Swedish Registry for Gallstone Surgery and ERCP (GallRiks) between 2006 and 2014 were studied. The primary outcome was PEP but we also studied other peri- and postoperative complication rates., Results: Data from 43,595 ERCP procedures were analyzed. In the subgroup of patients who received PS with a total diameter ≤ 5 Fr, the risk of PEP increased nearly four times compared to those who received PS with a total diameter of >5 Fr (OR 3.58; 95% CI 1.40-11.07). Furthermore, patients who received PS of >5 Fr and >5 cm had a significantly lower pancreatitis frequency compared to those with shorter stents of the same diameter (1.39% vs 15.79%; p  = 0.0033)., Conclusions: PS with a diameter of >5 Fr and a length of >5 cm seems to have a better protective effect against PEP, compared to shorter and thinner stents. However, in the present version of GallRiks it is not possible to differentiate the exact type of pancreatic stent (apart from material, length and diameter) that has been introduced, so our conclusion must be interpreted with caution.

Total pancreatectomy is associated with short- and long-term high complication rate and without evidence of oncologic advantages. Several metabolic consequences are co-related with the apancreatic state. The unstable diabetes related to the total resection of the pancreas expose the patients to short- and long-term life-threatening complications. Severe hypoglycemia is a short-term dangerous complication that can also cause patients' death. Chronic complications of severe diabetes (cardiac and vascular diseases, neuropathy, nephropathy, and retinopathy) are also cause of morbidity, mortality and worsening of quality of life. For this reasons the number of total pancreatectomies performed has certainly decreased over time. However, today there are still some indications for this kind of procedures. Chronic pancreatitis untreatable with conventional treatments, surgical treatment of precancerous pancreatic lesions, surgical treatment of locally advanced pancreatic cancer and the management of patients with extraordinary high-risk pancreatic texture after pancreaticoduodenectomy represent possible indications for total pancreatectomy and are analyzed in the present paper., Competing Interests: The authors declare that they have no conflict of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.