BackgroundCholecystectomy in patients with idiopathic acute pancreatitis (IAP) is controversial. A randomized trial found cholecystectomy to reduce the recurrence rate of IAP but did not include... Show moreBackgroundCholecystectomy in patients with idiopathic acute pancreatitis (IAP) is controversial. A randomized trial found cholecystectomy to reduce the recurrence rate of IAP but did not include preoperative endoscopic ultrasonography (EUS). As EUS is effective in detecting gallstone disease, cholecystectomy may be indicated only in patients with gallstone disease. This study aimed to determine the diagnostic value of EUS in patients with IAP, and the rate of recurrent pancreatitis in patients in whom EUS could not determine the aetiology (EUS-negative IAP).MethodsThis prospective multicentre cohort study included patients with a first episode of IAP who underwent outpatient EUS. The primary outcome was detection of aetiology by EUS. Secondary outcomes included adverse events after EUS, recurrence of pancreatitis, and quality of life during 1-year follow-up.ResultsAfter screening 957 consecutive patients with acute pancreatitis from 24 centres, 105 patients with IAP were included and underwent EUS. In 34 patients (32 per cent), EUS detected an aetiology: (micro)lithiasis and biliary sludge (23.8 per cent), chronic pancreatitis (6.7 per cent), and neoplasms (2.9 per cent); 2 of the latter patients underwent pancreatoduodenectomy. During 1-year follow-up, the pancreatitis recurrence rate was 17 per cent (12 of 71) among patients with EUS-negative IAP versus 6 per cent (2 of 34) among those with positive EUS. Recurrent pancreatitis was associated with poorer quality of life.ConclusionEUS detected an aetiology in a one-third of patients with a first episode of IAP, requiring mostly cholecystectomy or pancreatoduodenectomy. The role of cholecystectomy in patients with EUS-negative IAP remains uncertain and warrants further study. Show less
BACKGROUND: Acute resection for left-sided obstructive colon carcinoma is thought to be associated with a higher mortality risk than a bridge-to-surgery approach using decompressing stoma or self... Show moreBACKGROUND: Acute resection for left-sided obstructive colon carcinoma is thought to be associated with a higher mortality risk than a bridge-to-surgery approach using decompressing stoma or self-expandable metal stent, but prediction models are lacking.OBJECTIVE: This study aimed to determine the influence of treatment strategy on mortality within 90 days from the first intervention in patients presenting with left-sided obstructive colon carcinoma.DESIGN: This was a national multicenter cohort study that used data from a prospective national audit.SETTINGS: The study was performed in 75 Dutch hospitals.PATIENTS: Patients were included if they underwent resection with curative intent for left-sided obstructive colon carcinoma between 2009 and 2016.INTERVENTIONS: First intervention was either acute resection, bridge to surgery with self-expandable metallic stent, or bridge to surgery with decompressing stoma.MAIN OUTCOME MEASURES: The main outcome measure was 90-day mortality after the first intervention. Risk factors were identified using multivariable logistic analysis. Subsequently, a risk model was developed.RESULTS: In total, 2395 patients were included, with the first intervention consisting of acute resection in 1848 patients (77%), stoma as bridge to surgery in 332 patients (14%), and stent as bridge to surgery in 215 patients (9%). Overall, 152 patients (6.3%) died within 90 days from the first intervention. A decompressing stoma was independently associated with lower 90-day mortality risk (HR, 0.27; 95% CI, 0.094–0.62). Other independent predictors for mortality were age, ASA classification, tumor location, and index levels of serum creatinine and C-reactive protein. The constructed risk model had an area under the curve of 0.84 (95% CI, 0.81–0.87).LIMITATIONS: Only patients who underwent surgical resection were included.CONCLUSIONS: Treatment strategy had a significant impact on 90-day mortality. A decompressing stoma considerably lowers the risk of mortality, especially in older and frail patients. The developed risk model needs further external validation. Show less
BackgroundNeoadjuvant treatment for pancreatic ductal adenocarcinoma (PDAC) has increased, necessitating histopathologic confirmation of cancer. This study evaluates the performance of endoscopic... Show moreBackgroundNeoadjuvant treatment for pancreatic ductal adenocarcinoma (PDAC) has increased, necessitating histopathologic confirmation of cancer. This study evaluates the performance of endoscopic tissue acquisition (TA) procedures for borderline resectable and resectable PDAC.MethodsPathology reports of patients included in two nationwide randomized controlled trials (PREOPANC and PREOPANC-2) were reviewed. The primary outcome was sensitivity for malignancy (SFM), considering both “suspicious for” and “malignant” as positive. Secondary outcomes were rate of adequate sampling (RAS) and diagnoses other than PDAC.ResultsOverall, 892 endoscopic procedures were performed in 617 patients, including endoscopic ultrasonography (EUS)-guided TA in 550 (89.1%), endoscopic retrograde cholangiopancreatography (ERCP)-guided brush cytology in 188 (30.5%), and periampullary biopsies in 61 patients (9.9%). The SFM was 85.2% for EUS, 88.2% for repeat EUS, 52.7% for ERCP, and 37.7% for periampullary biopsies. The RAS ranged 94–100%. Diagnoses other than PDAC were other periampullary cancers in 24 (5.4%), premalignant disease in five (1.1%), and pancreatitis in three patients (0.7%).ConclusionsEUS-guided TA of patients with borderline resectable and resectable PDAC included in RCTs had an SFM above 85% for both first and repeat procedures, meeting international standards. Two percent had false positive result for malignancy and 5% had other (non-PDAC) periampullary cancers. Show less
BackgroundMalignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard... Show moreBackgroundMalignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a reasonable life expectancy and adequate performance status is a laparoscopic surgical gastrojejunostomy (SGJ). Recently, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) emerged as a promising alternative to the surgical approach. The present study aims to compare these treatment modalities in terms of efficacy, safety, and costs.MethodsThe ENDURO-study is a multicentre, open-label, parallel-group randomized controlled trial. In total, ninety-six patients with gastric outlet obstruction caused by an irresectable or metastasized malignancy will be 1:1 randomized to either SGJ or EUS-GE. The primary endpoint is time to tolerate at least soft solids. The co-primary endpoint is the proportion of patients with persisting or recurring symptoms of gastric outlet obstruction for which a reintervention is required. Secondary endpoints are technical and clinical success, quality of life, gastroenterostomy dysfunction, reinterventions, time to reintervention, adverse events, quality of life, time to start chemotherapy, length of hospital stay, readmissions, weight, survival, and costs.DiscussionThe ENDURO-study assesses whether EUS-GE, as compared to SGJ, results in a faster resumption of solid oral intake and is non-inferior regarding reinterventions for persistent or recurrent obstructive symptoms in patients with malignant GOO. This trial aims to guide future treatment strategies and to improve quality of life in a palliative setting. Show less
Bleeker, M.; Horst, A. van der; Bel, A.; Sonke, J.J.; Hooft, J.E. van; Pouw, R.E.; Hulshof, M.C.C.M. 2023
Background and study aims Fiducial markers have demonstrated clinical value in radiotherapy in several organs, but little is known about markers in the stomach. Here, we assess the technical... Show moreBackground and study aims Fiducial markers have demonstrated clinical value in radiotherapy in several organs, but little is known about markers in the stomach. Here, we assess the technical feasibility of endoscopic placement of markers in gastric cancer patients and their potential benefit for image-guided radiotherapy (IGRT).Patients and methods In this prospective feasibility study, 14 gastric cancer patients underwent endoscopy-guided gold (all patients) and liquid (7 patients) marker placements distributed throughout the stomach. Technical feasibility, procedure duration, and potential complications were evaluated. Assessed benefit for IGRT comprised marker visibility on acquired imaging (3–4 computed tomography [CT] scans and 19–25 cone-beam CTs [CBCTs] per patient) and lack of migration. Marker visibility was compared per marker type and location (gastroesophageal junction (i.e., junction/cardia), corpus (corpus/antrum/fundus), and pylorus).Results Of the 93 marker implantation attempts, 59 were successful, i.e., marker in stomach wall and present during entire 5-week radiotherapy course (2–6 successfully placed markers per patient), with no significant difference (Fisher’s exact test; P>0.05) in success rate between gold (39/66=59%) and liquid (20/27=74%). Average procedure duration was 24.4 min (range 16–38). No procedure-related complications were reported. All successfully placed markers were visible on all CTs, with 81% visible on ≥95% of CBCTs. Five markers were poorly visible (on <75% of CBCTs), possibly due to small marker volume and peristaltic motion since all five were liquid markers located in the corpus. No migration was observed.Conclusions Endoscopic placement of fiducial markers in the stomach is technically feasible and safe. Being well visible and positionally stable, markers provide a potential benefit for IGRT. Show less
Background and study aims Overcoming logistical obstacles for the implementation of colorectal endoscopic submucosal dissection (ESD) requires accurate prediction of procedure times. We aimed to... Show moreBackground and study aims Overcoming logistical obstacles for the implementation of colorectal endoscopic submucosal dissection (ESD) requires accurate prediction of procedure times. We aimed to evaluate existing and new prediction models for ESD duration.Patients and methods Records of all consecutive patients who underwent single, non-hybrid colorectal ESDs before 2020 at three Dutch centers were reviewed. The performance of an Eastern prediction model [GIE 2021;94(1):133-144] was assessed in the Dutch cohort. A prediction model for procedure duration was built using multivariable linear regression. The model's performance was validated using internal validation by bootstrap resampling, internal-external cross-validation and external validation in an independent Swedish ESD cohort.Results A total of 435 colorectal ESDs were analyzed (92% en bloc resections, mean duration 139 minutes, mean tumor size 39 mm). The performance of current unstandardized time scheduling practice was suboptimal (explained variance: R-2 =27%). We successfully validated the Eastern prediction model for colorectal ESD duration <60 minutes (c-statistic 0.70, 95% CI 0.62-0.77), but this model was limited due to dichotomization of the outcome and a relatively low frequency (14%) of ESDs completed <60 minutes in the Dutch centers. The model was more useful with a dichotomization cut-off of 120 minutes (c-statistic: 0.75; 88% and 17% of "easy" and "very difficult" ESDs completed <120 minutes, respectively). To predict ESD duration as continuous outcome, we developed and validated the six-variable cESD-TIME formula ( https://cesdtimeformula.shinyapps.io/calculator/ ; optimism-corrected R-2 =61%; R-2 =66% after recalibration of the slope).Conclusions We provided two useful tools for predicting colorectal ESD duration at Western centers. Further improvements and validations are encouraged with potential local adaptation to optimize time planning. Show less
Background: Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative indication for... Show moreBackground: Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative indication for surgery. We aimed to evaluate the role of CA19.9 monitoring for early detection and management in a cyst surveillance population. Methods: The PACYFIC-registry is a prospective collaboration that investigates the yield of pancreatic cyst surveillance performed at the discretion of the treating physician. We included participants for whom at least one serum CA19.9 value was determined by a minimum follow-up of 12 months. Results: Of 1865 PACYFIC participants, 685 met the inclusion criteria for this study (mean age 67 years, SD 10; 61% female). During a median follow-up of 25 months (IQR 24, 1966 visits), 29 participants developed high-grade dysplasia (HGD) or pancreatic cancer. At baseline, CA19.9 ranged from 1 to 591 kU/L (median 10 kU/L [IQR 14]), and was elevated (& GE;37 kU/L) in 64 participants (9%). During 191 of 1966 visits (10%), an elevated CA19.9 was detected, and these visits more often led to an intensified follow-up (42%) than those without an elevated CA19.9 (27%; p < 0.001). An elevated CA19.9 was the sole reason for surgery in five participants with benign disease (10%). The baseline CA19.9 value was (as continuous or dichotomous variable at the 37 kU/L threshold) not independently associated with HGD or pancreatic cancer development, whilst a CA19.9 of & GE; 133 kU/L was (HR 3.8, 95% CI 1.1-13, p = 0.03). Conclusions: In this pancreatic cyst surveillance cohort, CA19.9 monitoring caused substantial harm by shortening surveillance intervals (and performance of unnecessary surgery). The current CA19.9 cutoff was not predictive of HGD and pancreatic cancer, whereas a higher cutoff may decrease false-positive values. The role of CA19.9 monitoring should be critically appraised prior to implementation in surveillance programs and guidelines. Show less
BACKGROUNDS: planchnic vein thrombosis (SVT) is a major complication of moderate and severe acute pancreatitis. There is no consensus on whether therapeutic anticoagulation should be started in... Show moreBACKGROUNDS: planchnic vein thrombosis (SVT) is a major complication of moderate and severe acute pancreatitis. There is no consensus on whether therapeutic anticoagulation should be started in patients with acute pancreatitis and SVT. AIM: To gain insight into current opinions and clinical decision making of pancreatologists regarding SVT in acute pancreatitis. METHODS: A total of 139 pancreatologists of the Dutch Pancreatitis Study Group and Dutch Pancreatic Cancer Group were approached to complete an online survey and case vignette survey. The threshold to assume group agreement was set at 75%. RESULTS: The response rate was 67% (n = 93). Seventy-one pancreatologists (77%) regularly prescribed therapeutic anticoagulation in case of SVT, and 12 pancreatologists (13%) for narrowing of splanchnic vein lumen. The most common reason to treat SVT was to avoid complications (87%). Acute thrombosis was the most important factor to prescribe therapeutic anticoagulation (90%). Portal vein thrombosis was chosen as the most preferred location to initiate therapeutic anticoagulation (76%) and splenic vein thrombosis as the least preferred location (86%). The preferred initial agent was low molecular weight heparin (LMWH; 87%). In the case vignettes, therapeutic anticoagulation was prescribed for acute portal vein thrombosis, with or without suspected infected necrosis (82% and 90%), and thrombus progression (88%). Agreement was lacking regarding the selection and duration of long-term anticoagulation, the indication for thrombophilia testing and upper endoscopy, and about whether risk of bleeding is a major barrier for therapeutic anticoagulation. CONCLUSION: In this national survey, the pancreatologists seemed to agree on the use of therapeutic anticoagulation, using LMWH in the acute phase, for acute portal thrombosis and in the case of thrombus progression, irrespective of the presence of infected necrosis. Show less
BACKGROUND & AIMS: Recent pancreatic cancer surveil-lance programs of high-risk individuals have reported improved outcomes. This study assessed to what extent outcomes of pancreatic ductal... Show moreBACKGROUND & AIMS: Recent pancreatic cancer surveil-lance programs of high-risk individuals have reported improved outcomes. This study assessed to what extent outcomes of pancreatic ductal adenocarcinoma (PDAC) patients with a CDKN2A/p16 pathogenic variant diagnosed under surveillance are better as compared with patients with PDAC diagnosed outside surveillance.METHODS: In a pro-pensity score matched cohort using data from the Netherlands Cancer Registry, we compared resectability, stage, and survival between patients diagnosed under sur-veillance with non-surveillance patients with PDAC. Survival analyses were adjusted for potential effects of lead time.RESULTS: Between January 2000 and December 2020, 43,762 patients with PDAC were identified from the Netherlands Cancer Registry. Thirty-one patients with PDAC under surveillance were matched in a 1:5 ratio with 155 non surveillance patients based on age at diagnosis, sex, year diagnosis, and tumor location. Outside surveillance, 5.8% of the patients had stage I cancer, as compared with 38.7% of surveillance patients with PDAC (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19). In total, 18.7% of non surveillance patients vs 71.0% of surveillance patients un- derwent a surgical resection (OR, 10.62; 95% CI, 4.56-26.63). Patients in surveillance had a better prognosis, reflected by 5-year survival of 32.4% and a median overall survival of 26.8 months vs 4.3% 5-year survival and 5.2 months median overall survival in non-surveillance patients (hazard ratio, 0.31; 95% CI 0.19-0.50). For all adjusted lead times, survival remained significantly longer in surveillance patients than non-surveillance patients.CONCLUSION: Surveillance for PDAC in carriers of a CDKN2A/p16 pathogenic variant results in earlier detection, increased resectability, and improved survival as compared with non-surveillance patients with PDAC. Show less
INTRODUCTION: Necrotizing pancreatitis may result in a disrupted or disconnected pancreatic duct (DPD) with the potential for long-lasting negative impact on a patient's clinical outcome. There is... Show moreINTRODUCTION: Necrotizing pancreatitis may result in a disrupted or disconnected pancreatic duct (DPD) with the potential for long-lasting negative impact on a patient's clinical outcome. There is a lack of detailed data on the full clinical spectrum of DPD, which is critical for the development of better diagnostic and treatment strategies. METHODS: We performed a long-term post hoc analysis of a prospectively collected nationwide cohort of 896 patients with necrotizing pancreatitis (2005-2015). The median follow-up after hospital admission was 75 months (P25-P75: 41-151). Clinical outcomes of patients with and without DPD were compared using regression analyses, adjusted for potential confounders. Predictive features for DPD were explored. RESULTS: DPD was confirmed in 243 (27%) of the 896 patients and resulted in worse clinical outcomes during both the patient's initial admission and follow-up. During hospital admission, DPD was associated with an increased rate of new-onset intensive care unit admission (adjusted odds ratio [aOR] 2.52; 95% confidence interval [CI] 1.62-3.93), new-onset organ failure (aOR 2.26; 95% CI 1.45-3.55), infected necrosis (aOR 4.63; 95% CI 2.87-7.64), and pancreatic interventions (aOR 7.55; 95% CI 4.23-13.96). During long-term follow-up, DPD increased the risk of pancreatic intervention (aOR 9.71; 95% CI 5.37-18.30), recurrent pancreatitis (aOR 2.08; 95% CI 1.32-3.29), chronic pancreatitis (aOR 2.73; 95% CI 1.47-5.15), and endocrine pancreatic insufficiency (aOR 1.63; 95% CI 1.05-2.53). Central or subtotal pancreatic necrosis on computed tomography (OR 9.49; 95% CI 6.31-14.29) and a high level of serum C-reactive protein in the first 48 hours after admission (per 10-point increase, OR 1.02; 95% CI 1.00-1.03) were identified as independent predictors for developing DPD. DISCUSSION: At least 1 of every 4 patients with necrotizing pancreatitis experience DPD, which is associated with detrimental, short-term and long-term interventions, and complications. Central and subtotal pancreatic necrosis and high levels of serum C-reactive protein in the first 48 hours are independent predictors for DPD. Show less
Huijgevoort, N.C.M. van; Hoogenboom, S.A.M.; Lekkerkerker, S.J.; Busch, O.R.; Chiaro, M. del; Fockens, P.; ... ; Hooft, J.E. van 2023
Background: Follow-up in patients with intraductal papillary mucinous neoplasm (IPMN) aims to detect advanced neoplasia (high-grade dysplasia/cancer) in an early stage. The 2015 American... Show moreBackground: Follow-up in patients with intraductal papillary mucinous neoplasm (IPMN) aims to detect advanced neoplasia (high-grade dysplasia/cancer) in an early stage. The 2015 American Gastroentero-logical Association (AGA), 2017 International Association of Pancreatology (IAP), and the 2018 European Study Group on Cystic tumours of the Pancreas (European) guidelines differ in their recommendations on indications for surgery. However, it remains unclear which guideline is most accurate in predicting advanced neoplasia in IPMN. Methods: Patients who underwent surgery were extracted from a prospective database (January 2006-January 2021). In patients with IPMN, final pathology was compared with the indication for surgery according to the guidelines. ROC-curves were calculated to determine the diagnostic accuracy for each guideline. Results: Overall, 247 patients underwent surgery for cystic lesions. In 145 patients with IPMN, 52 had advanced neoplasia, of which the AGA guideline would have advised surgery in 14 (27%), the IAP and European guideline in 49 (94%) and 50 (96%). In 93 patients without advanced neoplasia, the AGA, IAP, and European guidelines would incorrectly have advised surgery in 8 (8.6%), 77 (83%) and 71 (76%). Conclusion: The European and IAP guidelines are clearly superior in detecting advanced neoplasia in IPMN as compared to the AGA, albeit at the cost of a higher rate of unnecessary surgery. To harmonize care and to avoid confusion caused by conflicting statements, a global evidence-based guideline for PCN in collaboration with the various guidelines groups is required once the current guidelines require an update. (c) 2023 Published by Elsevier B.V. on behalf of IAP and EPC. Show less
Sissingh, N.J.; Vries, B.A. de; Inderson, A.; Hoek, B. van; Heide, F. van der; Hooft, J.E. van 2023
Background and aims: Fully covered metal stents (FCSEMSs) are increasingly used for treatment of biliary anas-tomotic strictures (ASs) after liver transplantation (LT), requiring fewer endoscopic... Show moreBackground and aims: Fully covered metal stents (FCSEMSs) are increasingly used for treatment of biliary anas-tomotic strictures (ASs) after liver transplantation (LT), requiring fewer endoscopic interventions than does treat-ment with multiple plastic stents (MPSs). Previous studies, however, have reported adverse events such as stent migration and pancreatitis. The intraductal FCSEMS (ID-FCSEMS) potentially avoids these disadvantages. This study aimed to assess the efficacy and safety of ID-FCSEMSs compared with MPSs for AS.Methods: The cohorts of LT patients treated for AS with endoscopic stenting between 2010 and 2019 from 2 Dutch liver transplantation centers were retrospectively analyzed. Patients treated with ID-FCSEMSs or MPSs were included.Results: 80 patients (44 with ID-FCSEMSs vs 36 with MPSs) were included, with a median follow-up time of 52 versus 64 months (P = .183). Stricture resolution was 93% in the ID-FCSEMS versus 97% in the MPS group (P = 1.000) after a median of 19 and 26 weeks, respectively (P = .031). The median number of ERCPs was 2 in the ID-FCSEMS group versus 4 in the MPS group (P < .001). Stricture recurrence occurred in 33% of ID-FCSEMS versus 29% of MPS patients (P = .653) after a median of 24 and 55 weeks (P = .403). Stent migration occurred in 16% of ID-FCSEMS versus 39% of MPS patients (P = .020). Post-ERCP fever was observed in 34% of ID-FCSEMS patients compared with 14% of MPS patients (P = .038). No significant differences were found in pancreatitis rate between the groups, being 6.8% for ID-FCSEMSs and 5.6% for MPSs (P = .816).Conclusion: ID-FCSEMSs for the treatment of AS after LT provides similar stricture resolution and recurrence rates as MPSs, though with a significant reduction of procedures needed. Show less
Introduction: In patients with left-sided obstructive colon cancer (LSOCC), a stoma is often constructed as part of primary treatment, but with a considerable risk of becoming a permanent stoma (PS... Show moreIntroduction: In patients with left-sided obstructive colon cancer (LSOCC), a stoma is often constructed as part of primary treatment, but with a considerable risk of becoming a permanent stoma (PS). The aim of this retrospective multicentre cohort is to identify risk factors for a PS in LSOCC and to develop a pre-and postoperative prediction model for PS. Materials and methods: Data was retrospectively obtained from 75 hospitals in the Netherlands. Patients who had curative resection of LSOCC between January 1, 2009 to December 31, 2016 were included with a minimum follow-up of 6 months after resection. The interventions analysed were emergency resection, decompressing stoma or stent as bridge-to-elective resection. Main outcome measure was presence of PS at the end of follow-up. Multivariable logistic regression analysis was performed to identify risk factors for PS at primary presentation (T0) and after resection, in patients having a stoma in situ (T1). These risk factors were used to construct a web-based prediction tool. Results: Of 2099 patients included in the study (T0), 779 had a PS (37%). A total of 1275 patients had a stoma in situ directly after resection (T1), of whom 674 had a PS (53%). Median follow-up was 34 months. Multivariable analysis showed that older patients, female sex, high ASA-score and open approach were independent predictors for PS in both the T0 and T1 population. Other predictors at T0 were sigmoid location, low Hb, high CRP, cM1 stage, and emergency resection. At T1, subtotal colectomy, no primary anastomosis, not receiving adjuvant chemotherapy and high pTNM stage were additional predictors. Two predictive models were built, with an AUC of 0.74 for T0 and an AUC of 0.81 for T1. Conclusions: PS is seen in 37% of the patients who have resection of LSOCC. In patients with a stoma in situ directly after resection, 53% PS are seen due to non-reversal. Not only baseline characteristics, but also treatment strategies determine the risk of a PS in patients with LSOCC. The developed predictive models will give physicians insight in the role of the individual variables on the risk of a PS and help in informing the patient about the probability of a PS. (c) 2022 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Objective: Routine urgent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (ES) does not improve outcome in patients with predicted severe acute biliary... Show moreObjective: Routine urgent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (ES) does not improve outcome in patients with predicted severe acute biliary pancreatitis. Improved patient selection for ERCP by means of endoscopic ultrasonography (EUS) for stone/sludge detection may challenge these findings. Design: A multicentre, prospective cohort study included patients with predicted severe acute biliary pancreatitis without cholangitis. Patients underwent urgent EUS, followed by ERCP with ES in case of common bile duct stones/sludge, within 24 hours after hospital presentation and within 72 hours after symptom onset. The primary endpoint was a composite of major complications or mortality within 6 months after inclusion. The historical control group was the conservative treatment arm (n=113) of the randomised APEC trial (Acute biliary Pancreatitis: urgent ERCP with sphincterotomy versus conservative treatment, patient inclusion 2013-2017) applying the same study design. Results: Overall, 83 patients underwent urgent EUS at a median of 21 hours (IQR 17-23) after hospital presentation and at a median of 29 hours (IQR 23-41) after start of symptoms. Gallstones/sludge in the bile ducts were detected by EUS in 48/83 patients (58%), all of whom underwent immediate ERCP with ES. The primary endpoint occurred in 34/83 patients (41%) in the urgent EUS-guided ERCP group. This was not different from the 44% rate (50/113 patients) in the historical conservative treatment group (risk ratio (RR) 0.93, 95% CI 0.67 to 1.29; p=0.65). Sensitivity analysis to correct for baseline differences using a logistic regression model also showed no significant beneficial effect of the intervention on the primary outcome (adjusted OR 1.03, 95% CI 0.56 to 1.90, p=0.92). Conclusion: In patients with predicted severe acute biliary pancreatitis without cholangitis, urgent EUS-guided ERCP with ES did not reduce the composite endpoint of major complications or mortality, as compared with conservative treatment in a historical control group. Show less
Gorris, M.; Huijgevoort, N.C.M. van; Fockens, P.; Meijer, S.L.; Verheij, J.; Voermans, R.P.; ... ; Hooft, J.E. van 2023
Background: Endoscopic retrograde cholangiopancreatography (ERCP) with biliary brush cytology is commonly used to diagnose malignant pancreatobiliary strictures. This trial compared the sensitivity... Show moreBackground: Endoscopic retrograde cholangiopancreatography (ERCP) with biliary brush cytology is commonly used to diagnose malignant pancreatobiliary strictures. This trial compared the sensitivity of two intraductal brush cytology devices. Methods: A randomized controlled trial in which consecutive patients with suspected malignant, extrahepatic biliary strictures were randomized (1:1) to a dense or conventional brush cytology device. Primary endpoint was sensitivity. Interim analysis was conducted after 50% of the patients completed follow-up. Results were interpreted by a data safety monitoring board. Results: Between June 2016 and June 2021, 64 patients were randomized to the dense (27 patients, 42%) or conventional brush (37 patients, 58%). Malignancy was diagnosed in 60 patients (94%) and benign disease in 4 patients (6%). Diagnoses were confirmed by histopathology in 34 patients (53%), cytopathology in 24 patients (38%), and clinical or radiological follow up in 6 patients (9%). Sensitivity of the dense brush was 50%, compared to 44% for the conventional brush (p = 0 center dot 785). Discussion: The results of this randomized controlled trial showed that the sensitivity of a dense brush is not superior to a conventional brush for diagnosing malignant extrahepatic pancreatobiliary strictures. This trial was prematurely ended for reasons of futility. Show less
Gorris, M.; Huijgevoort, N.C.M. van; Fockens, P.; Meijer, S.L.; Verheij, J.; Voermans, R.P.; ... ; Hooft, J.E. van 2023
BackgroundEndoscopic retrograde cholangiopancreatography (ERCP) with biliary brush cytology is commonly used to diagnose malignant pancreatobiliary strictures. This trial compared the sensitivity... Show moreBackgroundEndoscopic retrograde cholangiopancreatography (ERCP) with biliary brush cytology is commonly used to diagnose malignant pancreatobiliary strictures. This trial compared the sensitivity of two intraductal brush cytology devices.MethodsA randomized controlled trial in which consecutive patients with suspected malignant, extrahepatic biliary strictures were randomized (1:1) to a dense or conventional brush cytology device. Primary endpoint was sensitivity. Interim analysis was conducted after 50% of the patients completed follow-up. Results were interpreted by a data safety monitoring board.ResultsBetween June 2016 and June 2021, 64 patients were randomized to the dense (27 patients, 42%) or conventional brush (37 patients, 58%). Malignancy was diagnosed in 60 patients (94%) and benign disease in 4 patients (6%). Diagnoses were confirmed by histopathology in 34 patients (53%), cytopathology in 24 patients (38%), and clinical or radiological follow up in 6 patients (9%). Sensitivity of the dense brush was 50%, compared to 44% for the conventional brush (p = 0·785).DiscussionThe results of this randomized controlled trial showed that the sensitivity of a dense brush is not superior to a conventional brush for diagnosing malignant extrahepatic pancreatobiliary strictures. This trial was prematurely ended for reasons of futility. Show less
Background: More accurate diagnosis of mucinous cysts will reduce the risk of unnecessary pancreatic surgery. Carcinoembryonic antigen (CEA) and glucose in pancreatic cyst fluid (PCF) can... Show moreBackground: More accurate diagnosis of mucinous cysts will reduce the risk of unnecessary pancreatic surgery. Carcinoembryonic antigen (CEA) and glucose in pancreatic cyst fluid (PCF) can differentiate mucinous from non-mucinous pancreatic cystic neoplasms (PCN). The current study assessed the value of combined CEA and glucose testing in PCF. Methods: Cross-sectional validation study including prospectively collected PCF from patients undergoing endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) and pancreatic surgery. We performed laboratory measurements for CEA and glucose and measured glucose levels by a hand glucometer. Primary outcome was diagnostic accuracy evaluated by receiver operator curves (ROC), sensitivity, specificity, positive, and negative predictive value (PPV, NPV). Results: Overall, PCF was collected from 63 patients, including 33 (52%) with mucinous and 30 (48%) with non-mucinous PCN. Histopathology (n = 36; 57%), cytopathology (n = 2; 3%), or clinical and/or radiological diagnosis (n = 25; 40%) was used as reference standard. Combined CEA (cut-off >= 192 ng/ml) and laboratory glucose testing (cut-off < 50 mg/dL) reached 92% specificity and 48% sensitivity, whereas either positive CEA (cut-off >= 20 ng/ml) or glucose testing (cut-off < 50 mg/ dL) showed 97% sensitivity and 50% specificity. Sensitivity and specificity were 80% and 68% for CEA >= 20 ng/mL versus 50% and 93% for CEA >= 192 ng/mL (the conventional cut-off level). Laboratory and glucometer glucose both reached 100% sensitivity and 60% and 45% specificity, respectively. None of the biomarkers and cut-offs reached a PPV exceeding 90%, whereas both glucose measurements had a NPV of 100% (i.e., high glucose excludes a mucinous cyst). Conclusion: Combined CEA and glucose testing in PCF reached high specificity and sensitivity for differentiating mucinous from non-mucinous PCN. Glucose testing, whether alone or combined with the new CEA cut-off (>= 20 ng/mL), reached > 95% sensitivity for mucinous cysts, whereas only glucose reached a NPV > 95%. Show less
Houvast, R.D.; Duijvenvoorde, M. van; Chua, J.; Vankemmelbeke, M.; Durrant, L.G.; Inderson, A.; ... ; Kuppen, P.J.K. 2023
Background: Targeted molecular imaging may improve tumor cell identification during diagnosis and resection of pancreatic ductal adenocarcinoma (PDAC). Although many molecular imaging biomarkers... Show moreBackground: Targeted molecular imaging may improve tumor cell identification during diagnosis and resection of pancreatic ductal adenocarcinoma (PDAC). Although many molecular imaging biomarkers are (over)expressed in PDAC, intertumoral heterogeneity of biomarker expression hampers universal tracer administration. Preoperative, patient-specific screening and selection of the most optimal biomarker could therefore improve tumor delineation. Objective: This study evaluated whether fine-needle biopsy (FNB) specimens could be used to preoperatively predict biomarker expression in the corresponding primary PDAC specimen. Methods: Expression of previously identified PDAC biomarkers alpha(v)beta(6), CEACAM5, EGFR, mesothelin, Le(a/c/x), and sdi-Le(a) on FNB and corresponding primary tumor (PT) specimens (n = 45) was evaluated using immunohistochemistry and quantified using a semi-automated image analysis workflow. Results: Biomarker expression on FNB and PT tissues showed high concordance ( increment H-score <= 50), i.e. was present in 62% of cases for alpha(v)beta(6), 61% for CEACAM5, 85% for EGFR, 69% for mesothelin, 76% for Le(a/c/x), and 79% for sdi-Le(a), indicating high concordance. Except for alpha(v)beta(6), biomarker expression on FNB tissues was positively correlated with PT expression for all biomarkers. Subgroup analyses showed that neoadjuvant therapy (NAT) had no major and/or significant effect on concordance, expression difference and, except for mesothelin, correlation of biomarker expression between FNB and PT tissues. Conclusion: This study demonstrated that biomarker expression in FNB tissues is predictive for PT expression, irrespective of the application of NAT. These findings thereby provide the foundation for the clinical application of an FNB-based biomarker-screening workflow, eventually facilitating a patient-specific approach of molecular imaging tracer administration in PDAC. Show less
