Chronic intestinal failure (CIF) patients are at risk for developing intestinal failure‐associated liver disease (IFALD), which can progress to end‐stage liver disease. Liver biopsy is the current reference standard to diagnose and monitor IFALD. However, due to its associated complications, biopsy is an unattractive tool in this respect. Our aim was to assess the evidence regarding non‐invasive assessment of IFALD in the adult population and provide ideas to take this field further. We searched the PubMed, EMBASE and Web of Science databases in accordance with the PRISMA guideline. We included studies in the adult/mixed intestinal failure population, performing non‐invasive diagnostic assessment of IFALD and using liver biopsy, 1H‐MRS or MRI‐PDFF as reference. Quality of the included studies was assessed using the QUADAS‐2 tool. Four studies were included, assessing two serum (vitamin B12, FGF21) and two imaging tests (Fibroscan, CAUS). Three used liver biopsy as reference, all according to a different histological scoring system. One used 1H‐MRS as reference. Vitamin B12 did not correlate with liver injury, Fibroscan did not correlate with fibrosis, but with cholestasis. FGF21 correlated with steatosis grade. Several CAUS parameters correlated with the degree of steatosis assessed by 1H‐MRS. In conclusion, three tests show promise to non‐invasively assess IFALD, but the limited data do not justify conclusions on the diagnostic value of the tested biomarkers. Hence, additional studies are needed. Identification of and validation for grading and staging of clinically relevant histomorphological parameters of IFALD is also crucial and a conceptual study set up is provided.

Purpose Laparoscopy-assisted transgastric endoscopic retrograde cholangiopancreatography (LAERCP) is an alternative for the anatomically challenging conventional ERCP in patients with a Roux-en-Y gastric bypass (RYGB) as it allows access to the biliary tree via the gastric remnant. We investigated the efficacy and safety of LAERCP. Material and Methods We retrospectively reviewed all charts from RYGB patients who underwent a LAERCP between January 2009 and August 2019 in a non-academic referral center for bariatric surgery. Patients who underwent pancreatic therapy were excluded. We collected demographic, clinical, and outcome data. An adverse event was defined as any complaint related to the LAERCP up to 30 days after the procedure and graded according to the ASGE lexicon. Results We identified 100 LAERCP in 86 patients with RYGB (70% female, median age 54 years). Same-session cholecystectomy was performed in 35 LAERCP (35%). The papilla of Vater was visualized in 100% of LAERCP with a therapeutic success rate of 94%. Stone extraction succeeded in 88.8% and sphincterotomy was performed in 96.7%. We identified 30 adverse events in 28 procedures, of which eight endoscopy-related, 14 laparoscopy-related, and eight non-specified (f.i. fever, allergic reaction). In total, six severe adverse events were reported concerning post-ERCP pancreatitis (n = 2), laparoscopy-related hemorrhage (n = 1), abscess (n = 1), shock (n = 1), and pneumonia (n = 1). No patient died due to LAERCP. Conclusion LAERCP is an effective and relatively safe procedure for biliary diseases in patients with RYGB.

RNF43 mutation analysis in serrated polyposis, sporadic serrated polyps and Lynch syndrome polyps Aims: RNF43 is suggested to be involved in the serrated pathway towards colorectal cancer and encodes a transmembrane Ring-type E3 ubiquitin ligase that negatively regulates the Wnt pathway. This study aimed to elucidate the role of RNF43 gene variants in serrated polyposis syndrome (SPS) and serrated polyps. Methods and results: Three cohorts were tested. The first cohort included germline DNA of 26 SPS patients tested for pathogenic variants in RNF43 by Sanger sequencing all exons. In the second cohort we tested somatic DNA for RNF43 mutations from sporadic serrated lesions: 25 hyperplastic polyps, 35 sessile serrated lesions and 38 traditional serrated adenomas (TSA). In the third cohort we investigated RNF43 mutations in 49 serrated polyps and 60 conventional adenomas from 40 patients with Lynch syndrome. No germline RNF43 pathogenic variants were detected in our SPS cohort. In sporadic colorectal lesions we detected RNF43 deleterious frameshift mutations in three TSA and one SSL. The RNF43 mutations in previously described homopolymeric hot-spots were detected in microsatellite-instable (MSI) polyps and the other RNF43 mutations in microsatellite-stable (MSS) serrated polyps. RNF43 hot-spot mutations were discovered in seven serrated polyps and 12 conventional adenomas from Lynch patients. Conclusion: Truncating germline RNF43 mutations are uncommon in SPS patients. Somatic mutations in RNF43 were found in sporadic TSA and SSL and both serrated polyps and adenomas from Lynch syndrome patients, suggesting that they do not develop early in the pathway to CRC and are not specific for serrated polyp subtypes.

Background: Proton pump inhibitor (PPI) indications are limited to gastrointestinal disorders and ulcer prophylaxis. Still, PPIs are among the most frequently prescribed drugs. Aim: To evaluate the appropriateness of PPI prescriptions and identify predictive factors for inappropriate PPI use. Design and Setting: Observational study using a Dutch primary care database with all new PPI prescriptions between 2016 and 2018. Methods: Individual patient data and details on PPI use were collected. Appropriateness of initiation and continuation of PPI prescriptions was evaluated using the applicable guidelines. Results: We evaluated 148,926 patients (≥ 18 years) from 27 general practices. A total of 23,601 (16%) patients started PPI therapy (mean age 57 ± 17 years, 59% female). Valid PPI indications at initiation were seen in 10,466 PPI users (44%). Predictors for inappropriately initiated PPI use were older age (OR 1.03, 95%CI 1.03-1.03), and use of non-selective NSAIDs (OR 5.15, 95%CI 4.70-5.65), ADP receptor inhibitors (OR 5.07, 95%CI 3.46-7.41), coxibs (OR 3.93, 95%CI 2.92-5.28) and low-dose aspirin (OR 3.83, 95%CI 3.07-4.77). Despite an initial valid indication, PPI use was inaccurately continued in 32% of patients on short-course therapy for dyspepsia and in 11% of patients on ulcer prophylaxis. Conclusion: More than half of PPI users in primary care seem to have an inappropriate indication with unnecessary ulcer prophylaxis related to drug use being one of the leading causes. Future initiatives to reduce PPI use for unnecessary ulcer prophylaxis and timely deprescription if PPI is no longer indicated, are needed.

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