Gallstones as a cause in presumed acute alcoholic pancreatitis: observational multicentre study.

BACKGROUND: Data on the incidence and clinical relevance of gallstones in patients with suspected acute alcoholic pancreatitis are lacking and are essential to minimize the risk of recurrent acute pancreatitis. The aim of this study was to assess the incidence of gallstones and the associated rate of recurrent acute pancreatitis in patients with presumed acute alcoholic pancreatitis. METHODS: Between 2008 and 2019, 23 hospitals prospectively enrolled patients with acute pancreatitis. Those diagnosed with their first episode of presumed acute alcoholic pancreatitis were included in this study. The term gallstones was used to describe the presence of cholelithiasis or biliary sludge found during imaging. The primary outcome was pancreatitis recurrence during 3 years of follow-up. RESULTS: A total of 334 patients were eligible for inclusion, of whom 316 were included in the follow-up analysis. Gallstone evaluation, either during the index admission or during follow-up, was performed for 306 of 334 patients (91.6%). Gallstones were detected in 54 patients (17.6%), with a median time to detection of 6 (interquartile range 0-42) weeks. During follow-up, recurrent acute pancreatitis occurred in 121 of 316 patients (38.3%), with a significantly higher incidence rate for patients with gallstones compared with patients without gallstones (59% versus 34.2% respectively; P < 0.001), while more patients with gallstones had stopped drinking alcohol at the time of their first recurrence (41% versus 24% respectively; P = 0.020). Cholecystectomy was performed for 19 patients with gallstones (36%). The recurrence rate was lower for patients in the cholecystectomy group compared with patients who did receive inadequate treatment or no treatment (5/19 versus 19/34 respectively; P = 0.038). CONCLUSION: Gallstones were found in almost one in every five patients diagnosed with acute alcoholic pancreatitis. Gallstones were associated with a higher rate of recurrent pancreatitis, while undergoing cholecystectomy was associated with a reduction in this rate.

Prospective multicentre study of indications for surgery in patients with idiopathic acute pancreatitis following endoscopic ultrasonography (PICUS).

BACKGROUND: Cholecystectomy 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). METHODS: This 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. RESULTS: After 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. CONCLUSION: EUS 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.

Some patients develop acute inflammation of the pancreas without a clear cause. These patients have a high risk of developing more episodes of acute inflammation of the pancreas. Potentially, such inflammation could be caused by tiny gallstones that physicians are not able to detect. If this is true, these patients may also benefit from surgical removal of the gallbladder. However, this is still controversial. Endoscopic ultrasonography is a diagnostic procedure during which a physician looks at the gallbladder and bile ducts in detail via a small ultrasound probe inserted through the mouth. This endoscopic ultrasonography may be able to detect gallstones better than physicians were able to previously. This study tested the value of endoscopic ultrasonography, and the number of patients who developed more episodes of acute inflammation after endoscopic ultrasonography was recorded. Some 106 patients with acute inflammation of the pancreas for the first time without a clear cause participated and were offered endoscopic ultrasonography. The number of times endoscopic ultrasonography found a cause for the acute inflammation was recorded, as well as safety parameters, number of patients who developed more episodes of acute inflammation, and quality of life. After screening 957 patients, 105 ultimately underwent endoscopic ultrasonography. A cause was found in one-third of patients. This was mostly (tiny) gallstones, but chronic inflammation and even tumours were found. These patients were mostly treated surgically for their gallstones and tumours. In the first year after the first acute episode of inflammation, the inflammation came back at least once in almost one in six patients in whom endoscopic ultrasonography did not find a cause. This occurred less in patients in whom a cause was found; the inflammation came back in 1 in 16 of these patients. It was also found that having inflammation coming back negatively affected quality of life. In this study, endoscopic ultrasonography was able to detect a cause in one-third of patients with first-time acute inflammation of the pancreas. In one in four patients, this cause could be treated by a surgical procedure. Whether surgical removal of the gallbladder can be helpful in patients in whom endoscopic ultrasonography is not able to detect an aetiology should be investigated in further studies.

Patient selection for urgent endoscopic retrograde cholangio-pancreatography by endoscopic ultrasound in predicted severe acute biliary pancreatitis (APEC-2): a multicentre prospective study.

OBJECTIVE: 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. TRIAL REGISTRATION NUMBER: ISRCTN15545919.

Cumulative sum learning curves guiding multicenter multidisciplinary quality improvement of EUS-guided tissue acquisition of solid pancreatic lesions.

Background and study aims In this study, we evaluated the performance of community hospitals involved in the Dutch quality in endosonography team regarding yield of endoscopic ultrasound (EUS)-guided tissue acquisition (TA) of solid pancreatic lesions using cumulative sum (CUSUM) learning curves. The aims were to assess trends in quality over time and explore potential benefits of CUSUM as a feedback-tool. Patients and methods All consecutive EUS-guided TA procedures for solid pancreatic lesions were registered in five community hospitals between 2015 and  2018. CUSUM learning curves were plotted for overall performance and for performance per center. The American Society of Gastrointestinal Endoscopy-defined key performance indicators, rate of adequate sample (RAS), and diagnostic yield of malignancy (DYM) were used for this purpose. Feedback regarding performance was provided on multiple occasions at regional interest group meetings during the study period. Results A total of 431 EUS-guided TA procedures in 403 patients were included in this study. The overall and per center CUSUM curves for RAS improved over time. CUSUM curves for DYM revealed gradual improvement, reaching the predefined performance target (70 %) overall, and in three of five contributing centers in 2018. Analysis of a sudden downslope development in the CUSUM curve of DYM in one center revealed temporary absence of a senior cytopathologist to have had a temporary negative impact on performance. Conclusions CUSUM-derived learning curves allow for assessment of best practices by comparison among peers in a multidisciplinary multicenter quality improvement initiative and proved to be a valuable and easy-to-interpret means to evaluate EUS performance over time.

Factors associated with the progression of gastric intestinal metaplasia: a multicenter, prospective cohort study.

Background and study aims Gastric cancer (GC) is usually preceded by premalignant gastric lesions (GPLs) such as gastric intestinal metaplasia (GIM). Information on risk factors associated with neoplastic progression of GIM are scarce. This study aimed to identify predictors for progression of GIM in areas with low GC incidence. Patients and methods The Progression and Regression of Precancerous Gastric Lesions (PROREGAL) study includes patients with GPL. Patients underwent at least two upper endoscopies with random biopsy sampling. Progression of GIM means an increase in severity according to OLGIM (operative link on gastric intestinal metaplasia) during follow-up (FU). Family history and lifestyle factors were determined through questionnaires. Serum Helicobacter pylori infection, pepsinogens (PG), gastrin-17 and GC-associated single nucleotide polymorphisms (SNPs) were determined. Cox regression was performed for risk analysis and a chi-squared test for analysis of single nucleotide polymorphisms. Results Three hundred and eight patients (median age at inclusion 61 years, interquartile range (IQR: 17; male 48.4 %; median FU 48 months, IQR: 24) were included. During FU, 116 patients (37.7 %) showed progression of IM and six patients (1.9 %) developed high-grade dysplasia or GC. The minor allele (C) on TLR4 (rs11536889) was inversely associated with progression of GIM (OR 0.6; 95 %CI 0.4-1.0). Family history (HR 1.5; 95 %CI 0.9-2.4) and smoking (HR 1.6; 95 %CI 0.9-2.7) showed trends towards progression of GIM. Alcohol use, body mass index, history of H. pylori infection, and serological markers were not associated with progression. Conclusions Family history and smoking appear to be related to an increased risk of GIM progression in low GC incidence countries. TLR4 (rs11536889) showed a significant inverse association, suggesting that genetic information may play a role in GIM progression.

Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance.

INTRODUCTION: Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. METHODS: This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1-6 years. Patients were defined 'low risk' if they fulfilled requirements for discharge, and 'high risk' if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined 'low risk' with progression of disease during follow-up (FU) were considered 'misclassified' as low risk. RESULTS: 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were 'misclassified', showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were 'misclassified'. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were 'misclassified'. Seven patients developed gastric cancer (GC) or dysplasia, four patients were 'misclassified' based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4-83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. CONCLUSION: One-third of patients that would have been discharged from GC surveillance, appeared to be 'misclassified' as low risk. One additional endoscopy will reduce this risk by 70%.

Optimizing cytological specimens of EUS-FNA of solid pancreatic lesions: A pilot study to the effect of a smear preparation training for endoscopy personnel on sample quality and accuracy.

BACKGROUND: In the absence of rapid on-side pathological evaluation, endoscopy staff generally "smears" endoscopic ultrasound guided fine needle aspiration (EUS-FNA) specimens on a glass slide. As this technique is vulnerable to preparation artifacts, we assessed if its quality could be improved through a smear-preparation-training for endoscopy staff. METHODS: In this prospective pilot study, 10 endosonographers and 12 endoscopy nurses from seven regional EUS-centers in the Netherlands were invited to participate in a EUS-FNA smear-preparation-training. Subsequently, post training slides derived from solid pancreatic lesions were compared to pre-training "control" slides. Primary outcome was to assess if the training positively affects smear quality and, consequently, diagnostic accuracy of EUS-FNA of solid pancreatic lesions. RESULTS: Participants collected and prepared 71 cases, mostly pancreatic head lesions (48%). Sixty-eight controls were selected from the pretraining period. The presence of artifacts was comparable for smears performed before and after training (76% vs 82%, P = .36). Likewise, smear cellularity (≥50% target cells) before and after training did not differ (44% (30/68) vs 49% (35/71), P = .48). Similar, no difference in diagnostic accuracy for malignancy was detected (P = .10). CONCLUSION: In this pilot EUS-FNA smear-preparation-training for endoscopy personnel, smear quality and diagnostic accuracy were not improved after the training. Based on these results, we plan to further study other training programs and possibilities.

Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS): study protocol for a nationwide prospective cohort study.

INTRODUCTION: Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. METHODS AND ANALYSIS: PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months. ETHICS AND DISSEMINATION: PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NL7066). Prospectively registered.

Urgent endoscopic retrograde cholangiopancreatography with sphincterotomy versus conservative treatment in predicted severe acute gallstone pancreatitis (APEC): a multicentre randomised controlled trial.

BACKGROUND: It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis. METHODS: In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133. FINDINGS: Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio [RR] 0·87, 95% CI 0·64-1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two [2%] of 117 in the urgent ERCP group vs 11 [10%] of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04-0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group. INTERPRETATION: In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis. FUNDING: The Netherlands Organization for Health Research and Development, Fonds NutsOhra, and the Dutch Patient Organization for Pancreatic Diseases.

Diagnostic yield and agreement on fine-needle specimens from solid pancreatic lesions : comparing the smear technique to liquid-based cytology.

Background and study aims The traditional "smear technique" for processing and assessing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is sensitive to artifacts. Processing and evaluation of specimens collected in a liquid medium, liquid-based cytology (LBC) may be a solution. We compared the diagnostic value of EUS-FNA smears to LBC in pancreatic solid lesions in the absence of rapid on-site evaluation (ROSE). Patients and methods Consecutive patients who required EUS-FNA of a solid pancreatic lesion were included in seven hospitals in the Netherlands and followed for at least 12 months. Specimens from the first pass were split into two smears and a vial for LBC (using ThinPrep and/or Cell block). Smear and LBC were compared in terms of diagnostic accuracy for malignancy, sample quality, and diagnostic agreement between three cytopathologists. Results Diagnostic accuracy for malignancy was higher for LBC (82 % (58/71)) than for smear (66 % (47/71), P  = 0.04), but did not differ when smears were compared to ThinPrep (71 % (30/42), P  = 0.56) or Cell block (62 % (39/63), P  = 0.61) individually. Artifacts were less often present in ThinPrep (57 % (24/42), P  = 0.02) or Cell block samples (40 % (25/63), P  < 0.001) than smears (76 % (54/71)). Agreement on malignancy was equally good for smears and LBC (ĸ = 0.71 versus ĸ = 0.70, P  = 0.98), but lower for ThinPrep (ĸ = 0.26, P  = 0.01) than smears. Conclusion After a single pass, LBC provides higher diagnostic accuracy than the conventional smear technique for EUS-FNA of solid pancreatic lesions in the absence of ROSE. Therefore, LBC, may be an alternative to the conventional smear technique, especially in centers lacking ROSE.

Collaboration of community hospital endosonographers improves diagnostic yield of endoscopic ultrasonography guided tissue acquisition of solid pancreatic lesions.

Background and study aims Endoscopic ultrasound (EUS)-guided tissue acquisition (TA) is the method of choice for establishing a pathological diagnosis of solid pancreatic lesions. Data on quality and yield of EUS-guided TA performed in community hospitals are lacking. A study was performed to determine and improve the diagnostic yield of EUS-guided TA in a group of community hospitals. Methods Following analysis of the last 20 EUS-guided TA procedures of solid pancreatic lesions performed in each of four community hospitals, a collaborative EUS interest group was formed and a prospective registry was started. During meetings of the interest group, feedback on results per center were provided and strategies for improvement were discussed. Results In the BEFORE team formation cohort, 80 procedures were performed in 66 patients. In the AFTER team formation cohort, 133 procedures were performed in 125 patients. After team formation, the rate of adequate sample increased from 80 % (95 %CI [0.7 - 0.9]) to 95 % (95 %CI [0.9 - 1.0]) , diagnostic yield of malignancy improved from 28 % (95 %CI [0.2 - 0.4]) to 64 % (95 % CI [0.6 - 0.7]), and sensitivity of malignancy improved from 63 % (95 %CI [0.4 - 0.8]) to 84 % (95 %CI [0.8 - 0.9]). Multivariate regression analysis revealed team formation to be the only variable significantly associated with an increased rate of adequate sample. Conclusions Formation of a regional EUS interest group with regular feedback on results per center, and discussions on methods and techniques used, significantly improved the outcome of EUS-guided TA procedures in patients with solid pancreatic lesions in community hospitals.

Surveillance of premalignant gastric lesions: a multicentre prospective cohort study from low incidence regions.

OBJECTIVE: International guidelines recommend endoscopic surveillance of premalignant gastric lesions. However, the diagnostic yield and preventive effect require further study. We therefore aimed to assess the incidence of neoplastic progression and to assess the ability of various tests to identify patients most at risk for progression. DESIGN: Patients from the Netherlands and Norway with a previous diagnosis of atrophic gastritis (AG), intestinal metaplasia (IM) or dysplasia were offered endoscopic surveillance. All histological specimens were assessed according to the updated Sydney classification and the operative link on gastric intestinal metaplasia (OLGIM) system. In addition, we measured serum pepsinogens (PG) and gastrin-17. RESULTS: 279 (mean age 57.9 years, SD 11.4, male/female 137/142) patients were included and underwent at least one surveillance endoscopy during follow-up. The mean follow-up time was 57 months (SD 36). Four subjects (1.4%) were diagnosed with high-grade adenoma/dysplasia or invasive neoplasia (ie, gastric cancer) during follow-up. Two of these patients were successfully treated with endoscopic submucosal dissection, while the other two underwent a total gastrectomy. Compared with patients with extended AG/IM (PGI/II≤3 and/or OGLIM stage III-IV), patients with limited AG/IM (PG I/II>3 and OLGIM stage 0-II) did not develop high-grade adenoma/dysplasia or invasive neoplasia during follow-up (p=0.02). CONCLUSION: In a low gastric cancer incidence area, a surveillance programme can detect gastric cancer at an early curable stage with an overall risk of neoplastic progression of 0.3% per year. Use of serological markers in endoscopic surveillance programmes may improve risk stratification.

Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial): study protocol for a randomized controlled trial.

BACKGROUND: Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant cholangitis, early ERC is not recommended in patients with mild biliary pancreatitis. Evidence on the role of routine early ERC with endoscopic sphincterotomy in patients without cholangitis but with biliary pancreatitis at high risk for complications is lacking. We hypothesize that early ERC with sphincterotomy improves outcome in these patients. METHODS/DESIGN: The APEC trial is a randomized controlled, parallel group, superiority multicenter trial. Within 24 hours after presentation to the emergency department, patients with biliary pancreatitis without cholangitis and at high risk for complications, based on an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 8 or greater, Modified Glasgow score of 3 or greater, or serum C-reactive protein above 150 mg/L, will be randomized. In 27 hospitals of the Dutch Pancreatitis Study Group, 232 patients will be allocated to early ERC with sphincterotomy or to conservative treatment. The primary endpoint is a composite of major complications (that is, organ failure, pancreatic necrosis, pneumonia, bacteremia, cholangitis, pancreatic endocrine, or exocrine insufficiency) or death within 180 days after randomization. Secondary endpoints include ERC-related complications, infected necrotizing pancreatitis, length of hospital stay and an economical evaluation. DISCUSSION: The APEC trial investigates whether an early ERC with sphincterotomy reduces the composite endpoint of major complications or death compared with conservative treatment in patients with biliary pancreatitis at high risk of complications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97372133 (date registration: 17-12-2012).

[A woman with abdominal pain after a meal]. / Een vrouw met progressieve buikpijn na een maaltijd.

A 57-year-old woman presented with pain in her upper right abdomen, since 3 days. Laboratory tests showed elevated inflammation markers and an increased amount of alkaline phosphatase. Abdominal CT showed a perforating object from the stomach, ending in the liver. Gastroscopy revealed that the object was a fish bone.