Background and study aims: Recognition of T1 colorectal cancer (CRC) is difficult, with sensitivities of 35-60% in Western countries. We evaluated the real-life effects of the implementation of the OPTICAL model, a recently developed structured and validated prediction model, in Dutch community hospitals. Patients and methods: In this prospective multicenter study, 383 endoscopists from 40 hospitals were invited to follow an e-learning on the OPTICAL-model, to increase sensitivity for detecting T1CRC in non-pedunculated polyps. Next, real-life recognition of T1CRC was evaluated in 25 hospitals. Endoscopic and pathologic reports of T1CRCs detected during the next year were collected retrospectively while endoscopists were unaware of this evaluation. Sensitivity for recognition of T1CRC, R0 resection rate, and treatment modality were compared for trained vs. untrained endoscopists and for recognised vs. unrecognised T1CRCs. Results: Within 1 year after the e-learning 251 endoscopists detected 528 non-pedunculated T1CRCs, 118 (47%) of the endoscopist were trained. T1CRCs had a median size of 20mm and were mainly located in the distal colorectum (66%). Trained endoscopists recognised T1CRCs more frequently than untrained endoscopists (sensitivity 74% vs. 62%; mixed model analysis OR 2.90; 95%CI 1.54-5.45. A higher rate of R0 resection was seen for T1CRCs detected by trained endoscopists (69% vs. 56%, OR 1.73; 95%CI 1.03-2.91). Conclusion: Training in optical recognition of T1CRCs in community hospitals was associated with an increase in sensitivity for T1CRCs. Recognition led to a higher rate of en bloc local excision, resulting in higher R0-resection rates. This may be an important step towards more organ-preserving strategies.

Aims Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with a high recurrence rate of up to 30%. We evaluated whether standardized EMR training could reduce the post-EMR recurrence rate in Dutch community hospitals.

Pruritus is a seriously disabling symptom accompanying many cholestatic liver disorders. Recent experimental evidence implicated the lysophospholipase, autotaxin (ATX), and its product, lysophosphatidic acid (LPA), as potential mediators of cholestatic pruritus. In this study, we highlight that increased serum ATX levels are specific for pruritus of cholestasis, but not pruritus of uremia, Hodgkin's disease, or atopic dermatitis. Treatment of patients with cholestasis with the bile salt sequestrant, colesevelam, but not placebo, effectively reduced total serum bile salts and fibroblast growth factor 19 levels, but only marginally altered pruritus intensity and ATX activity. Rifampicin (RMP) significantly reduced itch intensity and ATX activity in patients with pruritus not responding to bile salt sequestrants. In vitro, RMP inhibited ATX expression in human HepG2 hepatoma cells and hepatoma cells overexpressing the pregnane X receptor (PXR), but not in hepatoma cells in which PXR was knocked down. Treatment of severe, refractory pruritus by the molecular adsorbents recirculation system or nasobiliary drainage improved itch intensity, which, again, correlated with the reduction of ATX levels. Upon reoccurrence of pruritus, ATX activity returned to pretreatment values. Conclusion: Serum ATX activity is specifically increased in patients with cholestatic, but not other forms of, systemic pruritus and closely correlates with the effectiveness of therapeutic interventions. The beneficial antipruritic action of RMP may be explained, at least partly, by the PXR-dependent transcriptional inhibition of ATX expression. Thus, ATX likely represents a novel therapeutic target for pruritus of cholestasis. (HEPATOLOGY 2012)

Tytgat Institute for Liver and Intestinal Research and Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The etherlands; Departments of Dermatology and Allergology, University of Munich, Munich, Germany; Internal Medicine II Grosshadern, University of Munich, unich, Germany; Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of astroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands; Department of Gastroenterology, Kaunas University of Medicine, Kaunas, ithuania; **Department of Medicine and Liver Unit, Clinica Universitaria, Medical School and Center for Applied Medical Research (CIMA), University of Navarra, amplona, Spain; Maternal and Fetal Disease Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, England; and Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

Background and aims: Ursodeoxycholic acid (UDCA) has an established effect on liver bio-chemistries in primary biliary cirrhosis (PBC). Few studies have evaluated long-term laboratory treatment effects and data beyond 6 years are not available. The aim of this study was to assess the long-term evolution of liver biochemistries during prolonged treatment with UDCA in biochemically non-advanced PBC.Patients and methods: Prospective multicenter cohort study of patients with PBC with pretreatment normal bilirubin and albumin, treated with UDCA 13-15 mg/kg/day. At yearly intervals, follow-up data including serum bilirubin, alkaline phosphatase (ALP), transaminases, albumin and IgM were collected. Data were analyzed with a repeated measurement model.Results: Two hundred and twenty-five patients were included and followed during a median period of 10.3 years. Following 1-year treatment with UDCA 36-100% of the total biochemical improvement was achieved, the maximum response was observed after 3 years. After initial improvements, bilirubin and AST levels increased and albumin levels significantly decreased after 6-10 years. However, these changes were of limited magnitude. The beneficial effects on ALT and ALP were maintained while IgM continued to decrease.Conclusion: In non-advanced PBC the biochemical response to UDCA is maintained up to 15 years. The long-term evolution of bilirubin, albumin and ALT differs from that of ALP and AST. The mean IgM level normalised and levels continued to decrease during the period of follow-up. (C) 2010 Elsevier Masson SAS. All rights reserved.

Einleitung: Im Blut cholestatischer Patienten mit Juckreiz konnten wir Lysophosphatidsäure (LPA) als potenten neuronalen Aktivator identifizieren. LPA und Autotaxin (ATX), das LPA aus Lysophosphatidylcholin freisetzt, waren nur im Serum cholestatischer Patienten mit Juckreiz, nicht aber ohne Juckreiz erhöht. Wir untersuchten, ob das Therapieansprechen des Juckreizes cholestatischer Patienten mit Veränderungen der ATX-Aktivität korrelierte.

Einleitung: Verschiedene systemische Erkrankungen sind mit Juckreiz assoziiert, wobei dessen Pathogenese weitestgehend unklar ist. Wir konnten einen neuronalen Aktivator im Serum cholestatischer Patienten mit Juckreiz als Lysophosphatidsäure (LPA) identifizieren. LPA sowie Autotaxin (ATX), welches LPA aus Lysophosphatidylcholin freisetzt, waren ausschließlich in juckenden cholestatischen Patienten erhöht. Das Ziel dieser Studie war zu eruieren, ob LPA und ATX auch eine Rolle in der Pathogenese des Juckreizes bei Urämie, Hodgkin Lymphom, atopischer Dermatitis und Pruritus gravidarum spielt.