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CDKN2A-p16-Leiden mutation carriers have a substantial risk of developing pancreatic ductal adenocarcinoma (PDAC). One of the main clinical features of hereditary cancer is the development of multiple cancers. Since 2000, we have run a surveillance program for CDKN2A-p16-Leiden mutation carriers. The patients are offered a yearly MRI with optionally endoscopic ultrasound. In patients with a confirmed lesion, usually, a partial resection of the pancreas is recommended. A total of 18 PDAC (8.3%) were detected in 218 mutation carriers. In this report, we describe two CDKN2A-p16-Leiden patients with a synchronous and metachronous PDAC. Including two previously-reported cases, we identified four patients with multiple PDAC: two of 18 patients within the surveillance program (11%) and two patients with a proven CDKN2A-p16-Leiden mutation not participating in the surveillance program. In conclusion, this study demonstrated a high risk of developing multiple PDAC in CDKN2A-p16-Leiden mutation carriers. After detecting a primary tumor, it is very important to exclude the presence of a second synchronous tumor. Moreover, after a partial pancreatectomy for PDAC, close surveillance is necessary. In view of the current findings, offering a total pancreatectomy might be an appropriate option in patients with an early PDAC.

Background Post cholecystectomy syndrome is characterized as recurrence of symptoms as experienced before cholecystectomy. In rare cases, a remnant cystic duct is causing these symptoms and occasionally surgical resection is performed. During surgery, visualization of the biliary ducts could be difficult due to inflammation and dense adhesions. Case presentation In this article, we presented a 36-year old woman with post-cholecystectomy syndrome in which we evaluated the feasibility of near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) for visualization of the remnant cystic and common bile duct during robot-assisted surgery. Intraoperative visualization of the remnant biliary duct and other important structures was feasible, and resection of the remnant cystic duct was successfully performed under fluorescence guidance, without any complications. Conclusions NIR fluorescence imaging of the biliary ducts using ICG does not prolong the operating time, and could potentially decrease the operation time in difficult procedures, because of easy and fast detection of the biliary tract. Furthermore, it is a non-hazardous and non-invasive technique, as it does not require use of radiation and cannot cause bile duct injury. This case illustrated that ICG NIR fluorescence imaging during difficult robot-assisted surgical procedures of the bile ducts is effective and therefore highly recommended.

Abstract Bariatric surgery is the most effective treatment for obesity and improves several manifestations of the metabolic syndrome, including nonalcoholic fatty liver disease. Strict nutritional counseling after bariatric surgery is a key in realizing these outcomes. When postoperative nutrient intake or nutrient uptake is compromised, bariatric surgery can also lead to severe hepatic complications. Here, we describe 3 cases of acute liver injury and acute liver failure caused by bariatric surgery, all with different management strategies and outcomes.

BackgroundEndoscopic retrograde cholangiopancreatography (ERCP) with fully covered self-expandable metal stent (FCSEMS) placement is the preferred approach for biliary drainage in patients with suspected distal malignant biliary obstruction (MBO). However, FCSEMS placement is associated with a high risk of post-ERCP pancreatitis (PEP). Endoscopic sphincterotomy prior to FCSEMS placement may reduce PEP risk.ObjectiveTo compare endoscopic sphincterotomy to no sphincterotomy prior to FCSEMS placement.DesignThis multicentre, randomised, superiority trial was conducted in 17 hospitals and included patients with suspected distal MBO. Patients were randomised during ERCP to receive either endoscopic sphincterotomy (sphincterotomy group) or no sphincterotomy (control group) prior to FCSEMS placement. The primary outcome was PEP within 30 days. Secondary outcomes included procedure-related complications and 30-day mortality. An interim analysis was performed after 50% of patients (n=259) had completed follow-up.ResultsBetween May 2016 and June 2023, 297 patients were included in the intention-to-treat analysis, with 156 in the sphincterotomy group and 141 in the control group. After the interim analysis, the study was terminated prematurely due to futility. PEP did not differ between groups, occurring in 26 patients (17%) in the sphincterotomy group compared with 30 patients (21%) in the control group (relative risk 0.78, 95% CI 0.49 to 1.26, p=0.37). There were no significant differences in bleeding, perforation, cholangitis, cholecystitis or 30-day mortality.ConclusionThis trial found that endoscopic sphincterotomy was not superior to no sphincterotomy in reducing PEP in patients with distal MBO. Therefore, there was insufficient evidence to recommend routine endoscopic sphincterotomy prior to FCEMS placement.Trial registration numberNL5130.

This study aimed to determine the ability of single fiber reflectance (SFR) spectroscopy incorporated in endoscopic ultrasound fine needle biopsy (EUS-FNB) procedures in the pancreas to distinguish benign and malignant pancreatic tissue in patient with pancreatic masses suspected for malignancy. This study was designed as a prospective observational single center study and included consecutive adult patients, who were scheduled for EUS-FNB of a solid pancreatic mass suspected for pancreatic ductal adenocarcinoma (PDAC). In total, seven optical parameters, derived from the absorption acquired spectra, were analyzed: blood volume fraction (BVF), microvascular saturation, average vessel diameter, bilirubin concentration (BIL), Mie amplitude, Mie slope and Rayleigh amplitude. Forty-five patients with a suspicious pancreatic lesion undergoing EUS-FNB were included, of which most of the patients (N=34) were ultimately diagnosed with PDAC. Finally, 27 out of 45 (60.0%) patients were used for the final analysis of the optical parameters. The median (IQR) BVF differed significantly in benign compared to malignant tissue (0.86 [0.30-2.03] and 4.49 [1.28-15.47]; =0.046). Combining BVF and BIL to a new parameter ( ) improved the discrimination between PDAC and benign pancreatic tissue ( =0.026). The area under the curve of was 0.84, resulting in a 92.8%, 75.0%, 97.5%, 50.0% and 91.3% sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for detection of PDAC. Differentiation between PDAC and benign pancreatic tissue using SFR spectroscopy during EUS-FNB procedures is promising. Future work should focus on comparing the diagnostic performance combining SFR spectroscopy with EUS-FNB and EUS-FNB alone.

Background Malignant 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. Methods The 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. Discussion The 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. Trial registration International Clinical Trials Registry Platform (ICTRP): NL9592. Registered on 07 July 2021.

Background 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. Methods 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. Discussion 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. Trial registration ClinicalTrials.gov NCT05750966, registered on March 2nd, 2023.

To improve the diagnostic value of fine-needle aspiration (FNA)-derived material, we perform targeted next-generation sequencing (NGS) in patients with a suspect lesion of the pancreas. The NGS analysis can lead to a change in the treatment plan or supports inconclusive or uncertain cytology results. We describe the advantages of NGS using one particular patient with a recurrent pancreatic lesion 7 years after resection of a pancreatic ductal adenocarcinoma (PDAC). Our NGS analysis revealed the presence of a presumed second primary cancer in the pancreatic remnant, which led to a change in treatment: resection with curative intend instead of palliation. Additionally, NGS identified an unexpected germline CDKN2A 19-base pair deletion, which predisposed the patient to developing PDAC. Preoperative NGS analysis of FNA-derived DNA can help identify patients at risk for developing PDAC and define future therapeutic options.

Background 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 α v β 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 (∆H-score ≤ 50), i.e. was present in 62% of cases for α v β 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 α v β 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. Graphical Abstract

Background CDKN2A‐p16‐Leiden mutation carriers have a high lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC), with very poor survival. Surveillance may improve prognosis. Objective To assess the cost‐effectiveness of surveillance, as compared to no surveillance. Methods In 2000, a surveillance program was initiated at Leiden University Medical Center with annual MRI and optional endoscopic ultrasound. Data were collected on the resection rate of screen‐detected tumors and on survival. The Kaplan–Meier method and a parametric cure model were used to analyze and compare survival. Based on the surveillance and survival data from the screening program, a state‐transition model was constructed to estimate lifelong outcomes. Results A total of 347 mutation carriers participated in the surveillance program. PDAC was detected in 31 patients (8.9%) and the tumor could be resected in 22 patients (71.0%). Long‐term cure among patients with resected PDAC was estimated at 47.1% (p < 0.001). The surveillance program was estimated to reduce mortality from PDAC by 12.1% and increase average life expectancy by 2.10 years. Lifelong costs increased by €13,900 per patient, with a cost‐utility ratio of €14,000 per quality‐adjusted life year gained. For annual surveillance to have an acceptable cost‐effectiveness in other settings, lifetime PDAC risk needs to be 10% or higher. Conclusion The tumor could be resected in most patients with a screen‐detected PDAC. These patients had considerably better survival and as a result annual surveillance was found to be cost‐effective.