Search

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life.Methods/design: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide.Discussion: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life.Trial Registration: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018. [ABSTRACT FROM AUTHOR]

Abstract Background In predicted severe acute pancreatitis, infections have a negative effect on clinical outcome. A start of enteral nutrition (EN) within 24 hours of onset may reduce the number of infections as compared to the current practice of starting an oral diet and EN if necessary at 3-4 days after admission. Methods/Design The PYTHON trial is a randomised controlled, parallel-group, superiority multicenter trial. Patients with predicted severe acute pancreatitis (Imrie-score ≥ 3 or APACHE-II score ≥ 8 or CRP > 150 mg/L) will be randomised to EN within 24 hours or an oral diet and EN if necessary, after 72 hours after hospital admission. During a 3-year period, 208 patients will be enrolled from 20 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of mortality or infections (bacteraemia, infected pancreatic or peripancreatic necrosis, pneumonia) during hospital stay or within 6 months following randomisation. Secondary endpoints include other major morbidity (e.g. new onset organ failure, need for intervention), intolerance of enteral feeding and total costs from a societal perspective. Discussion The PYTHON trial is designed to show that a very early (< 24 h) start of EN reduces the combined endpoint of mortality or infections as compared to the current practice of an oral diet and EN if necessary at around 72 hours after admission for predicted severe acute pancreatitis. Trial Registration ISRCTN: ISRCTN18170985

Background: Retrospective analysis to investigate the relationship between the flow-metabolic phenotype and overall survival (OS) of pancreatic ductal adenocarcinoma (PDAC) and its potential clinical utility., Methods: Patients with histopathologically proven PDAC between 2005 and 2014 using tumor attenuation on routine pre-operative CECT as a surrogate for the vascularity and [ 18 F]FDG-uptake as a surrogate for metabolic activity on [ 18 F]FDG-PET., Results: In total, 93 patients (50 male, 43 female, median age 63) were included. Hypoattenuating PDAC with high [ 18 F]FDG-uptake has the poorest prognosis (median OS 7 ± 1 months), compared to hypoattenuating PDAC with low [ 18 F]FDG-uptake (median OS 11 ± 3 months; p = 0.176), iso- or hyperattenuating PDAC with high [ 18 F]FDG-uptake (median OS 15 ± 5 months; p = 0.004) and iso- or hyperattenuating PDAC with low [ 18 F]FDG-uptake (median OS 23 ± 4 months; p = 0.035). In multivariate analysis, surgery combined with tumor differentiation, tumor stage, systemic therapy and flow metabolic phenotype remained independent predictors for overall survival., Discussion: The novel qualitative flow-metabolic phenotype of PDAC using a combination of CECT and [ 18 F]FDG-PET features, predicted significantly worse survival for hypoattenuating-high uptake pancreatic cancers compared to the other phenotypes., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Endoscopic resection of lesions involving the appendiceal orifice remains a challenge. We aimed to report outcomes with the full-thickness resection device (FTRD) for the resection of appendiceal lesions and identify factors associated with the occurrence of appendicitis., Methods: This was a retrospective study at 18 tertiary-care centers (USA 12, Canada 1, Europe 5) between November 2016 and August 2020. Consecutive patients who underwent resection of an appendiceal orifice lesion using the FTRD were included. The primary outcome was the rate of R0 resection in neoplastic lesions, defined as negative lateral and deep margins on post-resection histologic evaluation. Secondary outcomes included the rates of: technical success (en bloc resection), clinical success (technical success without need for further surgical intervention), post-resection appendicitis, and polyp recurrence., Results: 66 patients (32 women; mean age 64) underwent resection of colonic lesions involving the appendiceal orifice (mean [standard deviation] size, 14.5 (6.2) mm), with 40 (61 %) being deep, extending into the appendiceal lumen. Technical success was achieved in 59/66 patients (89 %), of which, 56 were found to be neoplastic lesions on post-resection pathology. Clinical success was achieved in 53/66 (80 %). R0 resection was achieved in 52/56 (93 %). Of the 58 patients in whom EFTR was completed who had no prior history of appendectomy, appendicitis was reported in 10 (17 %), with six (60 %) requiring surgical appendectomy. Follow-up colonoscopy was completed in 41 patients, with evidence of recurrence in five (12 %)., Conclusions: The FTRD is a promising non-surgical alternative for resecting appendiceal lesions, but appendicitis occurs in 1/6 cases., Competing Interests: S. Thakkar is a consultant for Boston Scientific; S. Kothari is a consultant for Boston Scientific and Cook Medical; T.E. Kowalski is a consultant for Boston Scientific and Medtronic; R.Z. Sharaiha is a consultant for Boston Scientific, Lumendi, and Olympus, and has received grant/research Support from Cook Medical; S. Mahadev is a consultant for Lumendi and Olympus; S. Friedland is a consultant for CapsoVision; B. Tharian is a consultant and speaker for Boston Scientific, and a speaker for Medtronic; S. Irani is a consultant for Boston Scientific; A.S. Ross is a consultant for Boston Scientific; A. Nett is a consultant for Boston Scientific; M.A. Khashab is a consultant for Boston Scientific, Medtronic, and Olympus. The remaining authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: A novel self-assembling peptide (SAP) can be applied to the post-endoscopic mucosal resection (EMR) defect to treat oozing bleedings. It has been suggested to stimulate early healing of damaged vessels. We hypothesized that SAP application could prevent delayed bleeding (DB) after EMR and performed a prospective cohort study to determine feasibility and safety., Methods: A total of 48 consecutive patients who underwent EMR between June 2018 and August 2019 for large lesions in the esophagus, duodenum (> 1 cm) or colorectum (> 2 cm) were treated with adjuvant SAP application. Duration and ease of SAP application were measured, as well as DB outcome., Results: The EMR defects of 48 patients were treated with SAP; 17 in the esophagus, 13 in the duodenum and 18 in the colorectum. SAP was easy to apply on the EMR defect with a median duration of 2.0 min. A dose of 3 cc was generally enough to cover a defect between 10 and 50 mm. An exploratory analysis of the prophylactic ability of SAP showed that 15.9% of patients (7/44) treated with SAP still had a DB, mostly in the duodenum (4/11). No adverse events related to gel exposure were reported., Conclusions: SAP application after EMR was found to be feasible and safe, and did not delay the procedure; however, DB was still relatively common. Future comparative studies are needed to evaluate whether SAP is able to reduce DB after EMR, particularly for lesions with an increased bleeding risk, such as in the duodenum.

Background: Guidelines advise self-expanding metal stents (SEMS) over plastic stents in preoperative endoscopic biliary drainage (EBD) for malignant extrahepatic biliary obstruction. This study aims to assess nationwide practice and outcomes., Methods: Patients with pancreatic head and periampullary cancer who underwent EBD before pancreatoduodenectomy were included from the Dutch Pancreatic Cancer Audit (2017-2018). Multivariable logistic and linear regression models were performed., Results: In total, 575/1056 patients (62.0%) underwent preoperative EBD: 246 SEMS (42.8%) and 329 plastic stents (57.2%). EBD-related complications were comparable between the groups (44/246 (17.9%) vs. 64/329 (19.5%), p = 0.607), including pancreatitis (22/246 (8.9%) vs. 25/329 (7.6%), p = 0.387). EBD-related cholangitis was reduced after SEMS placement (10/246 (4.1%) vs. 32/329 (9.7%), p = 0.043), which was confirmed in multivariable analysis (OR 0.36 95%CI 0.15-0.87, p = 0.023). Major postoperative complications did not differ (58/246 (23.6%) vs. 90/329 (27.4%), p = 0.316), whereas postoperative pancreatic fistula (24/246 (9.8%) vs. 61/329 (18.5%), p = 0.004; OR 0.50 95%CI 0.27-0.94, p = 0.031) and hospital stay (14.0 days vs. 17.4 days, p = 0.005; B 2.86 95%CI -5.16 to -0.57, p = 0.014) were less after SEMS placement., Conclusion: This study found that preoperative EBD frequently involved plastic stents. SEMS seemed associated with lower risks of cholangitis and less postoperative pancreatic fistula, but without an increased pancreatitis risk., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Accurately diagnosing indeterminate biliary strictures is challenging but important for patient prognostication and further management. Biopsy sampling under direct cholangioscopic vision might be superior to standard ERCP techniques such as brushing or biopsy sampling. Our aim was to investigate whether digital single-operator cholangioscopy (DSOC) compared with standard ERCP workup improves the diagnostic yield in patients with indeterminate biliary strictures., Methods: Patients with an indeterminate biliary stricture on the basis of MRCP were randomized to standard ERCP visualization with tissue brushing (control arm [CA]) or DSOC visualization and DSOC-guided biopsy sampling (study arm [SA]). This was a prospective, international, multicenter trial with a procedure-blinded pathologist., Results: The first sample sensitivity of DSOC-guided biopsy samples was significantly higher than ERCP-guided brushing (SA 68.2% vs CA 21.4%, P < .01). The sensitivity of visualization (SA 95.5% vs CA 66.7%, P = .02) and overall accuracy (SA 87.1% vs CA 65.5%, P = .05) were significantly higher in the SA compared with the CA, whereas specificity, positive predictive value, and negative predictive value showed no significant difference. Adverse events were equally low in both arms., Conclusions: DSOC-guided biopsy sampling was shown to be safe and effective with a higher sensitivity compared with standard ERCP techniques in the visual and histopathologic diagnosis of indeterminate biliary strictures. (Clinical trial registration number: NCT03140007.)., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: In patients with acute recurrent pancreatitis (ARP), pancreas divisum, and no other etiologic factors, endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy (miES) is often performed to enlarge the minor papillary orifice, based on limited data. The aims of this study are to describe the rationale and methodology of a sham-controlled clinical trial designed to test the hypothesis that miES reduces the risk of acute pancreatitis., Methods: The SpHincterotomy for Acute Recurrent Pancreatitis (SHARP) trial is a multicenter, international, sham-controlled, randomized trial comparing endoscopic ultrasound + ERCP with miES versus endoscopic ultrasound + sham for the management of ARP. A total of 234 consented patients having 2 or more discrete episodes of acute pancreatitis, pancreas divisum confirmed by magnetic resonance cholangiopancreatography, and no other clear etiology for acute pancreatitis will be randomized. Both cohorts will be followed for a minimum of 6 months and a maximum of 48 months., Results: The trial is powered to detect a 33% risk reduction of acute pancreatitis frequency., Conclusions: The SHARP trial will determine whether ERCP with miES benefits patients with idiopathic ARP and pancreas divisum. Trial planning has informed the importance of blinded outcome assessors and long-term follow-up.

Introduction: Treatment of chronic calcifying pancreatitis is challenging and requires an interdisciplinary approach including endoscopist, surgeon and radiologist. With advances in endoscopic technology therapeutic interventions in the pancreatic duct became available. Extracorporeal shock wave lithotripsy (ESWL) is still recommended to be first line treatment, hence peroral pancreatoscopy- (POP) -guided intracorporal lithotripsy is a promising supplement in endoscopic therapy especially if ESWL is unsuccessful or not available., Evidence Aquisition: Evidence from published trials, abstracts and case reports on direct pancreatoscopic treatment of main pancreatic duct (MPD) stones was reviewed with focus on efficiency and safety of available technologies, endoscopes and lithotripsy devices. A systematic Medline and Cochrane Database search for relevant studies was performed., Evidence Synthesis: Seventeen relevant publications meeting the inclusion criteria have been identified (two prospective series, seven retrospective trials, six case reports, two abstracts, for a total of 225 patients). Successful ductal clearance for POP-guided treatment was reported between 37.5% and 100%. Clinical success was reported between 74% and 100%. Adverse event (AE) rate for POP-guided therapy is reported with 0-30%. There is no reported mortality following POP treatment. Three ongoing trials found to be registered., Conclusions: POP-guided lithotripsy seems to be a promising alternative in a very selected patient cohort. Good powered randomized controlled trials are needed to prove efficiency and safety of the new technique also for large numbers of patients before it can be recommended as general practice. The focus of future studies should not only be on technical success, but also clinical success and patient-reported outcomes (quality of life).

Background and Objective: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most prevalent complication after ERCP with an incidence of 3.5%. PEP severity is classified according to either the consensus criteria or the revised Atlanta criteria. In this international cohort study we investigated which classification is the strongest predictor of PEP-related mortality., Methods: We reviewed 13,384 consecutive ERCPs performed between 2012 and 2017 in eight hospitals. We gathered data on all pancreatitis-related adverse events and compared the predictive capabilities of both classifications. Furthermore, we investigated the correlation between the two classifications and identified reasons underlying length of stay., Results: The total sample consisted of 387 patients. The revised Atlanta criteria have a higher sensitivity (100 vs. 55%), specificity (98 vs. 72%) and positive predictive value (58 vs. 5%). There is a significant difference ( p  < 0.001) between the two classifications. In 124 patients (32%), the length of stay was influenced by concomitant diseases., Conclusion: The revised Atlanta classification is superior in predicting mortality and better reflects PEP severity. This has important implications for researchers, clinicians and patients. For the diagnosis of PEP pancreatitis, the consensus criteria remain the golden standard. However, the revised Atlanta criteria are preferable for defining PEP severity.

Background/objectives: Acute pancreatitis (AP) progresses to necrotizing pancreatitis in 15% of cases. An important pathophysiological mechanism in AP is third spacing of fluids, which leads to intravascular volume depletion. This results in a reduced splanchnic circulation and reduced venous return. Non-visualisation of the portal and splenic vein on early computed tomography (CT) scan, which might be the result of smaller vein diameter due to decreased venous flow, is associated with infected necrosis and mortality in AP. This observation led us to hypothesize that smaller diameters of portal system veins (portal, splenic and superior mesenteric) are associated with increased severity of AP., Methods: We conducted a post-hoc analysis of data from two randomized controlled trials that included patients with predicted severe and mild AP. The primary endpoint was AP-related mortality. The secondary endpoints were (infected) necrotizing pancreatitis and (persistent) organ failure. We performed additional CT measurements of portal system vein diameters and calculated their prognostic value through univariate and multivariate Poisson regression., Results: Multivariate regression showed a significant inverse association between splenic vein diameter and mortality (RR 0.75 (0.59-0.97)). Furthermore, there was a significant inverse association between splenic and superior mesenteric vein diameter and (infected) necrosis. Diameters of all veins were inversely associated with organ failure and persistent organ failure., Conclusions: We observed an inverse relationship between portal system vein diameter and morbidity and an inverse relationship between splenic vein diameter and mortality in AP. Further research is needed to test whether these results can be implemented in predictive scoring systems., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: The hypothesis is that decision-making for transfusion varies considerably among gastroenterologists. The aim is to identify preferences and predictors of transfusion decision-making in chronic anemia., Study Design and Methods: Between February and April of 2015, a computerized adaptive choice-based conjoint survey was administered to gastroenterologists in the Netherlands. The survey included seven patient attributes: hemoglobin levels, hemoglobin stability, age, iron indices, the presence of anemia-related symptoms, cardiovascular comorbidities, and the number of transfusions in the past half year. Predictors of transfusion preferences were assessed by multivariable regression., Results: 113 gastroenterologists completed the survey (response rate = 29%; mean age = 47 years; 24% women). Absolute hemoglobin level was the most important incentive of transfusion, accounting for 42% of decision-making, followed by age (15%), hemoglobin stability (12%), anemia-related symptoms (10%), and cardiovascular comorbidities (10%). A hemoglobin level >9.6 g/dL is an inflection point, where gastroenterologists would not prescribe transfusions. Age of the patient is more important in the decision-making process to younger gastroenterologists (OR -2.9, 95% CI -5.3 to -0.5)., Conclusion: Absolute hemoglobin level is the most important factor to transfusion decision-making. This is contradictory to transfusion guidelines for chronic anemia which address the importance of symptoms.