Genetic and serological markers to identify phenotypic subgroups in a Dutch Crohn's disease population

Background and aims. Both genetic and microbial factors seem to play a pivotal role in the aetiopathogenesis of Crohn's disease. The CARD15 frameshift mutation might link host genetic factors and the indigenous microbial flora, since CARD15 expression is stimulated by peptidoglycan, thereby activating NF-kappaB. It is hypothesised that CARD15 mutation carriers have defective anti-microbial reactions, resulting in more penetrating lesions and antibody responses, which are now being used as highly specific markers for Crohn's disease. The serological marker anti-Saccharomyces cerevisiae antibody directed against cell wall oligomannosidic epitopes has high specificity for Crohn's disease. Perinuclear anti-neutrophil cytoplasmic antibodies have been found in a subgroup of Crohn's disease patients, mostly with colonic involvement. Methods. We investigated the incidence of two CARD15 mutations (3020insC and 2722G > C), anti-S. cerevisiae antibody, and perinuclear anti-neutrophil cytoplasmic antibody in 108 (73F/35M) patients with Crohn's disease with a mean duration of disease since diagnosis of 16 (1-41) years in relation to their phenotype, according to the Vienna classification. Results. The prevalence of CARD15 frameshift mutation was 21%. Of all patients, 62% were anti-S. cerevisiae antibody positive, and 9% had perinuclear anti-neutrophil cytoplasmic antibodies. The prevalence of both anti-S. cerevisiae antibodies and perinuclear anti-neutrophil cytoplasmic antibodies was higher in the mutation carriers compared to non-carriers. Remarkably, all patients with a CARD15 mutation and positive anti-S. cerevisiae antibody had ileal disease. Carriership of the mutation was significantly associated with penetrating behaviour of the disease and weakly associated with stricturing behaviour. Furthermore, anti-S. cerevisiae antibody was associated with ileal disease involvement. Finally, most perinuclear anti-neutrophil cytoplasmic antibody positive patients showed ulcerative-like behaviour of disease (by means of colonic localisation). Conclusions. Genetic and serologic markers might be useful in defining patient subgroups. This may result in a more accurate prediction of disease behaviour, prognosis and therapeutic approach. (C) 2003 Editrice Gastroenterologica Italiana S.H. Published by Elsevier Ltd. All rights reserved

Endoscopic trimodal imaging versus standard video endoscopy for detection of early Barrett's neoplasia: a multicenter, randomized, crossover study in general practice

Background: Endoscopic trimodal imaging (ETMI) may improve detection of early neoplasia in Barrett's esophagus (BE). Studies with ETMI so far have been performed in tertiary referral settings only. Objective: To compare ETMI with standard video endoscopy (SVE) for the detection of neoplasia in BE patients with an intermediate-risk profile. Design: Multicenter, randomized, crossover study. Setting: Community practice. Patients and Methods: BE patients with confirmed low-grade intraepithelial neoplasia (LGIN) underwent both ETMI and SVE in random order (interval 6-16 weeks). During ETMI BE was inspected with high-resolution endoscopy followed by autofluorescence imaging (AFI). All visible lesions were then inspected with narrow-band imaging. During ETMI and SVE, visible lesions were sampled followed by 4-quadrant random biopsies every 2 cm. Main Outcome Measurements: Overall histological yield of ETMI and SVE and targeted histological yield of ETMI and SVE. Results: A total of 99 patients (79 men, 63 10 years) underwent both procedures. ETMI had a significantly higher targeted histological yield because of additional detection of 22 lesions with LGIN/high-grade intraepithelial neoplasia (EIGIN)/carcinoma (Ca) by AFT. There was no significant difference in the overall histological yield (targeted + random) between ETMI and SVE. HGIN/Ca was diagnosed only by random biopsies in 6 of 24 patients and 7 of 24 patients, with ETMI and SVE, respectively. Limitations: Inspection, with high-resolution endoscopy and AFT, was performed sequentially. Conclusion: ETMI performed in a community-based setting did not improve the overall detection of dysplasia compared with SVE. The diagnosis of dysplasia is still being made in a significant number of patients by random biopsies. Patients with a confirmed diagnosis of LGIN have a significant risk of HGIN/Ca. (Clinical trial registration number: ISRCTN91816824; NTR867.) (Gastrointest Endosc 2011;73:195-203.