Acute cholangitis is an infection of the biliary tract that is managed with adequate biliary drainage combined with antibiotic treatment. The international Tokyo Guidelines 2018 recommend 4 to 7 days of antibiotic treatment after adequate biliary drainage, but observational data suggest shorter treatment may be sufficient. We assessed whether 1 day of antibiotic treatment is non-inferior to 4–7 days of antibiotic treatment for acute cholangitis after adequate biliary drainage. The COBRA-trial is a multicentre, open-label, parallel group randomized controlled non-inferiority trial with blinded outcome assessment. A total of 416 patients with acute cholangitis will be randomly assigned in a 1:1 ratio to the intervention group (1 day of antibiotic treatment after adequate biliary drainage) or to the control group (4–7 days of antibiotic treatment after adequate biliary drainage). Patients with acute cholangitis due to common bile duct stones, benign or malignant distal biliary obstruction, or distal biliary stent dysfunction are eligible. Randomization will take place once adequate biliary drainage is achieved by ERCP. Main exclusion criteria are concomitant pancreatitis, liver abscess, cholecystitis, and another infectious diagnosis at the time of randomization, use of systemic maintenance antibiotics, and specific immunosuppressants. Patients will be stratified for blood culture results at the time of randomization and aetiology of cholangitis. The primary endpoint is clinical cure, defined as the patient being symptom-free by day 14, with no relapse or death occurring by day 30. Secondary endpoints include 30-day and 90-day all-cause mortality, relapse of cholangitis by day 90, time from ERCP to first relapse, any other subsequent infection requiring antibiotic treatment within 90 days, duration of initial hospital stay, number of days treated with antibiotics by day 30, subsequent infections with multidrug resistant (MDR) bacteria, quality of life, and cost-effectiveness. This trial assesses whether a short course of antibiotic treatment for acute cholangitis is as safe and effective compared to a longer course of antibiotic treatment. If confirmed, the results could substantially reduce antibiotic exposure and healthcare resource utilization, thereby contributing to global efforts to minimize unnecessary antibiotic treatment. ClinicalTrials.gov NCT05750966, registered on March 2nd, 2023.

BACKGROUND:Suboptimal human-artificial intelligence (AI) interaction is a potential roadblock for implementation of AI in clinical practice. We aimed to evaluate the interaction between AI and endoscopists in the optical diagnosis of colorectal carcinoma (CRC). METHODS:International endoscopists were invited to diagnose colorectal lesions online. After a pretest of 15 videos, the diagnosis could be adjusted in the subsequent 35 videos after receiving a simulated AI diagnosis. Histology was the gold standard. Endoscopists' diagnoses before and after AI were compared using the signal detection theory. Inappropriate response to AI was defined as decreased diagnostic performance by the endoscopist after AI. RESULTS:In 2730 diagnoses, the 78 participating endoscopists reached diagnostic accuracies of 71.4 % before and 73.7 % after AI (P < 0.001). Before AI, endoscopists missed only a few true CRCs (mean hit rate 0.86), at the cost of a mean false alarm rate of 0.35. Inappropriate response to AI was observed in 28.2 % of endoscopists. After AI, most endoscopists (41.0 %) shifted toward a more conservative attitude, tending to diagnose a lesion as non-CRC. CONCLUSIONS:Inappropriate response to AI is an issue in human-AI interaction for the optical diagnosis of CRC. Before using AI, endoscopists should become familiar with their own optical diagnostic performance, and that of the AI system, to possibly improve interaction.

ImportancePatients with painful chronic pancreatitis and a dilated pancreatic duct can be treated by early surgery or an endoscopy-first approach.ObjectiveTo compare long-term clinical outcomes of early surgery vs an endoscopy-first approach using follow-up data from the ESCAPE randomized clinical trial.Design, Setting, and ParticipantsBetween April 2011 and September 2018, 88 patients with painful chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach in 30 hospitals in the Netherlands collaborating in the Dutch Pancreatitis Study Group as part of the ESCAPE randomized clinical trial. For the present cohort study, long-term clinical data were collected after the initial 18-month follow-up. Follow-up was completed in June 2022, and data analysis was performed in June 2023.ExposurePatients with chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach.Main Outcomes and MeasuresThe primary end point was pain, assessed by the Izbicki pain score; secondary end points included patient-reported complete pain relief and satisfaction. Predefined subgroups included patients who progressed from endoscopy to surgery and those with ductal clearance obtained by endoscopy. Analysis was performed according to the intention-to-treat principle.ResultsIn this cohort study, 86 of 88 overall patients could be evaluated, with a mean (SD) follow-up period of 98 (16) months. Of 88 initial patients, 21 patients (24%) were female, and mean (SD) patient age was 61 (10) years. At the end of long-term follow-up, the mean (SD) Izbicki pain score was significant lower (33 [31] vs 51 [31]) in the early surgery group, as was the rate of patient-reported complete pain relief (14 of 31 patients [45%] vs 6 of 30 patients [20%]), compared to the endoscopy-first group. After the initial 18-month follow-up, 11 of 43 patients in the early surgery group (26%) underwent reinterventions vs 19 of 43 patients in the endoscopy-first group (44%). At the end of follow-up, more patients in the early surgery group were “very satisfied” with their treatment (22 of 31 patients [71%] vs 10 of 30 patients [33%]). Patients who progressed from endoscopy to surgery (22 of 43 patients [51%]) had significantly worse mean (SD) Izbicki pain scores (33 [31] vs 52 [24]) compared to the early surgery group and had a lower rate of complete pain relief (55% for early surgery vs 12% for endoscopy first). In the endoscopy-first group, patients with endoscopic ductal clearance had similar mean (SD) Izbicki pain scores as the remaining patients (49 [34] vs 53 [28]).Conclusions and RelevanceIn this cohort study evaluating long-term outcomes of the ESCAPE randomized clinical trial, after approximately 8 years of follow-up, early surgery was superior to an endoscopy-first approach in patients with painful chronic pancreatitis and a dilated main pancreatic duct in pain scores and patient satisfaction. Notably, patients who progressed from endoscopy to surgery had worse outcomes compared to patients undergoing early surgery, and obtaining endoscopic ductal clearance did not improve outcomes.

Aims Endoscopic full thickness resection (eFTR) is increasingly used as a minimally invasive diagnostic and potential therapeutic approach for smaller (≤2cm) T1 colorectal cancer (CRC). EFTR enables transmural resection, providing optimal histological risk assessment and complete (R0) resection, even in deep submucosal invasive cancer (D-SMIC). However, follow-up (FU) outcomes have not yet been described. This study aims to describe the medium-term oncological outcomes of eFTR for T1CRC.

Background and study aims Tissue acquisition is required for diagnosis of subepithelial lesions (SELs). However, obtaining adequate tissue remains challenging. This study investigated an EUS-guided technique using a forceps to create a channel and take multiple biopsies from the center of the lesion, therefore called endoscopic ultrasound-guided keyhole biopsy (EUS-KB). Patients and methods A retrospective cohort study was conducted in 56 patients with SELs in the upper gastrointestinal tract who were scheduled to undergo EUS-KB. The primary aim was to assess diagnostic yield, defined as the percentage of procedures where EUS-KB resulted in a definitive histopathological diagnosis. Furthermore, factors influencing diagnostic yield were investigated. Additional outcomes included technical success and adverse events. Results Technical success was achieved in 55 of 60 biopsies (91.7%). EUS-KB provided a diagnosis in 44 of 55 biopsies (80.0%), histology mostly showing gastrointestinal stromal tumor or leiomyoma. The diagnostic yield was not significantly influenced by the size or location of the SEL. Adverse events occurred in one patient (1.7%). Conclusions EUS-KB is a feasible and safe technique for obtaining a classifying diagnosis for SELs in the upper gastrointestinal tract. It could offer an alternative diagnostic modality, especially in lesions smaller than 20 mm.

Background The diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation Sequencing (NGS) performed on cytological material obtained with fine needle aspiration (FNA) or biliary duct brushing can speed up this process. Here, we study the incremental value of NGS for establishing the correct diagnosis, and subsequent treatment plan in patients with inconclusive diagnosis after regular diagnostic work-up for suspect pancreatic lesions. Methods In this prospective cross-sectional cohort study, patients were screened for inclusion in four hospitals. NGS was performed with AmpliSeq Cancer Hotspot Panel v2 and v4b in patients with inconclusive cytology results or with an uncertain diagnosis. Diagnostic results were evaluated by the oncology pancreatic multidisciplinary team. The added value of NGS was determined by comparing diagnosis (malignancy, cystic lesion or benign condition) and proposed treatment plan (exploration/resection, neoadjuvant chemotherapy, follow-up, palliation or repeated FNA) before and after integration of NGS results. Final histopathological analysis or a 6-month follow-up period were used as the reference standard in case of surgical intervention or non-invasive treatment, respectively. Results In 50 of the 53 included patients, cytology material was sufficient for NGS analysis. Diagnosis before and after integration of NGS results differed in 24% of the patients. The treatment plan was changed in 32% and the diagnosis was substantiated by the NGS data in 44%. Repetition of FNA/brushing was prevented in 14% of patients. All changes in treatment plan were correctly made after integration of NGS. Integration of NGS increased overall diagnostic accuracy from 68% to 94%. Interpretation This study demonstrates the incremental diagnostic value of NGS in patients with an initial inconclusive diagnosis. Integration of NGS results can prevent repeated EUS/FNA, and can also rigorously change the final diagnosis and treatment plan.

Abstract 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.

ObjectiveLumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited.DesignPatients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs.ResultsA total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention—5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference −€6348, bias-corrected and accelerated 95% CI −€26 386 to €10 121).ConclusionOur comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable.

Background and study aims: Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) is critical to determine subsequent treatment. Endoscopic Full-Thickness Resection (eFTR) is a new treatment option for T1 CRC <2cm. We aim to report clinical outcomes and short-term results. Patients and methods: Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analysed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk-assessment, curative resections, adverse events and short-term outcomes. Results: We included 330 procedures: 132 primary resections and 198 secondary scar resections after incomplete T1 CRC resection. Overall technical success, R0 resection and curative resection rates were 87.0% (95% CI [82.7 – 90.3%]), 85.6% (95% CI [81.2 – 89.2%]) and 60.3% (95% CI [54.7 – 65.7%]). Curative resection rate for primary resected T1 CRC was 23.7% (95% CI [15.9 – 33.6%]) and 60.8% (95% CI [50.4 – 70.4%]) after excluding deep submucosal invasion as risk-factor. Risk-stratification was possible in 99.3%. Severe adverse event rates was 2.2%. Additional oncologic surgery was performed in 49/320 (15.3%), with residual cancer in 11/49 (22.4%). Endoscopic follow-up was available in 200/242 (82.6%), with a median of 4 months and residual cancer in 1 (0.5%) following an incomplete resection. Conclusions: eFTR is a relatively safe and effective method to resect small T1 CRC, both as primary and secondary treatment. eFTR can expand endoscopic treatment options for T1 CRC and could help to reduce surgical overtreatment. Future studies should focus on long-term outcomes.

Infected necrotizing pancreatitis is a potentially lethal disease that generally requires invasive intervention. The endoscopic step-up approach is preferred over a surgical step-up approach in eligible patients. Although lumen-apposing metal stents (LAMS) are increasingly used, superiority in comparison with double-pigtail plastic stents (DPS) is not proven. LAMS might optimize endoscopic drainage and reduce the need for endoscopic necrosectomy. Nevertheless, some safety concerns, particularly the risk of bleeding, remain. We conducted a multicenter prospective study to investigate the clinical outcome of LAMS in patients with infected necrotizing pancreatitis.

Endoscopic treatment of large laterally spreading tumors (LSTs) with a focus of submucosally invasive colorectal cancer (T1 CRC) can be challenging. We evaluated outcomes of a hybrid resection technique using piecemeal endoscopic mucosal resection (pEMR) and endoscopic full-thickness resection (eFTR) in patients with large colonic LSTs containing suspected T1 CRC. Six hybrid pEMR-eFTR procedures for T1 CRCs were registered in a nationwide eFTR registry between July 2015 and December 2019. In all cases, the invasive part of the lesion was successfully isolated with eFTR; with eFTR, histologically complete resection of the invasive part was achieved in 5 /6 patients (83.3 %). No adverse events occurred during or after the procedure. The median follow-up time was 10 months (range 6–27), with all patients having undergone ≥ 1 surveillance colonoscopy. One patient had a small adenomatous recurrence, which was removed endoscopically. In conclusion, hybrid pEMR-eFTR is a promising noninvasive treatment modality that seems feasible for a selected group of patients with large LSTs containing a small focus of T1 CRC.

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.

For T1 colorectal cancer (CRC) endoscopic resection is an attractive alternative to surgical resection due to lower morbidity and mortality. However, conventional polypectomy often leads to suboptimal histologic risk assessment. Exact risk stratification with certainty about resection margin status and presence of histological risk factors for lymph node metastasis (LNM) is crucial for further decision making. endoscopic full-thickness resection (eFTR) could serve as a valid diagnostic and therapeutic treatment option for T1 CRC.

BACKGROUND:Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions ≤ 30 mm unsuitable for conventional endoscopic resection. This study reports clinical outcomes from the Dutch colorectal eFTR registry. METHODS:Consecutive patients undergoing eFTR in 20 hospitals were prospectively included. The primary outcome was technical success, defined as macroscopic complete en bloc resection. Secondary outcomes were: clinical success, defined as tumor-free resection margins (R0 resection); full-thickness resection rate; and adverse events. RESULTS : Between July 2015 and October 2018, 367 procedures were included. Indications were difficult polyps (non-lifting sign and/or difficult location; n = 133), primary resection of suspected T1 colorectal cancer (CRC; n = 71), re-resection after incomplete resection of T1 CRC (n = 150), and subepithelial tumors (n = 13). Technical success was achieved in 308 procedures (83.9 %). In 21 procedures (5.7 %), eFTR was not performed because the lesion could not be reached or retracted into the cap. In the remaining 346 procedures, R0 resection was achieved in 285 (82.4 %) and full-thickness resection in 288 (83.2 %). The median diameter of resected specimens was 23 mm. Overall adverse event rate was 9.3 % (n = 34/367): 10 patients (2.7 %) required emergency surgery for five delayed and two immediate perforations and three cases of appendicitis. CONCLUSION : eFTR is an effective and relatively safe en bloc resection technique for complex colorectal lesions with the potential to avoid surgery. Further studies assessing the role of eFTR in early CRC treatment with long-term outcomes are needed.

Goals: The aim of our study was to examine differences in length of hospital stay (LOHS) between patients with lower gastrointestinal bleeding who received either an early colonoscopy (within 24 h of presentation) or a standard colonoscopy (within 1 to 3 d). Background: Diagnostic management of lower gastrointestinal bleeding has been extensively debated in recent literature, especially whether colonoscopy within 24 hours of presentation is feasible and safe. Study: In this single center, nonblinded, randomized controlled trial, patients presenting at the emergency department with acute hematochezia were eligible if they required hospital admission. A total of 132 patients were included. Primary outcome was LOHS. Secondary outcomes included yield of colonoscopy, blood transfusion requirements, recurrent bleedings, complications, interventions related to complications, and 30-day mortality. The follow-up period was 1 month. Results: In total, 63 patients were randomized for <24 hours colonoscopy and 69 for standard colonoscopy. In the intention to treat analysis, LOHS was significantly lower in patients that underwent an early colonoscopy, compared with the standard group: median 2.0 days (inter quartile range, 2.0 to 4.0) versus median 3.0 days (inter quartile range, 2.0 to 4.0) (P=0.009). Recurrent bleedings and hospital readmissions were significantly more frequent in the <24-hour group: 13% versus 3% (P=0.04) and 11% versus 2% (P=0.02), respectively. No difference was observed regarding the number of patients diagnosed with a confirmed or presumptive bleeding source. In both groups, blood transfusion rate was similar and 30-day mortality was 0. Conclusions: Early colonoscopy reduces LOHS, but also results in lower clinical efficacy compared with standard colonoscopy.

Heterotopic pancreas is a relatively uncommon congenital anomaly, defined as pancreatic tissue in ectopic sites without an anatomic and vascular continuity with the main body of the pancreas. We report the case of a 58-year-old woman who was admitted to the hospital with the clinical suspicion of a mild, acute pancreatitis. Computed tomography, magnetic resonance imaging, transabdominal ultrasound, and endoscopic ultrasound revealed a normal orthotopic pancreas and the suspicion of a large heterotopic pancreas in the small bowel mesentery with signs of acute inflammation. The diagnosis of mesenteric heterotopic pancreatitis was preoperatively confirmed by endoscopic ultrasound-guided fine-needle aspiration and consequently histologically established after surgical resection.

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.