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The ReBus cohort is a matched nested case–control cohort of patients with nondysplastic (ND) Barrett's esophagus (BE) at baseline who progressed (progressors) or did not progress (nonprogressors) to high-grade dysplasia (HGD) or cancer. This cohort is constructed using the most stringent inclusion criteria to optimize explorative studies on biomarkers predicting malignant progression in NDBE. These explorative studies may benefit from expanding the number of cases and by incorporating samples that allow assessment of the biomarker over space (spatial variability) and over time (temporal variability). To (i) update the ReBus cohort by identifying new progressors and (ii) identify progressors and nonprogressors within the updated ReBus cohort containing spatial and temporal information. The ReBus cohort was updated by identifying Barrett's patients referred for endoscopic work-up of neoplasia at 4 tertiary referral centers. Progressors and nonprogressors with a multilevel (spatial) endoscopy and additional prior (temporal) endoscopies were identified to evaluate biomarkers over space and over time. The original ReBus cohort consisted of 165 progressors and 723 nonprogressors. We identified 65 new progressors meeting the same strict selection criteria, resulting in a total number of 230 progressors and 723 matched nonprogressors in the updated ReBus cohort. Within the updated cohort, 61 progressors and 107 nonprogressors (mean age 61 ± 10 years) with a spatial endoscopy (median level 3 [2–4]) were identified. 33/61 progressors and 50/107 nonprogressors had a median of 3 (2–4) additional temporal endoscopies. Our updated ReBus cohort consists of 230 progressors and 723 matched nonprogressors using the most strict selection criteria. In a subgroup of 168 Barrett's patients (the SpaTemp cohort), multiple levels have been sampled at baseline and during follow-up providing a unique platform to study spatial and temporal distribution of biomarkers in BE. [ABSTRACT FROM AUTHOR]

Background and Study Aims: We have recently proposed a classification of mucosal morphology in Barrett's esophagus based on three criteria: regularity of mucosal pattern, regularity of vascular pattern, and presence of abnormal blood vessels. We aimed to evaluate the interobserver agreement with the proposed mucosal morphology classification and to assess the additional value of narrow band imaging (NBI) over high resolution white light endoscopy (HR-WLE)., Patients and Methods: Five international experts in the field of Barrett's imaging and seven community endoscopists with no expertise in this field independently evaluated magnified still images from 50 areas, obtained with HR-WLE and NBI, in Barrett's esophagus patients. Visual analogue scales (VAS) were used for scoring imaging quality. Interobserver agreement for mucosal morphology and yield for identifying early neoplasia were assessed., Results: Imaging qualities of NBI were rated more highly than HR-WLE, when evaluated separately as well as in a side-by-side comparison. The interobserver agreement ranged from 0.40 to 0.56 and did not significantly differ between expert and non-expert endoscopists. The overall yield for correctly identifying images of early neoplasia was 81 % for HR-WLE, 72 % for NBI and 83 % for HR-WLE + NBI, with no significant difference between experts and non-experts., Conclusion: Interobserver agreement for the classification of mucosal morphology was moderate. Although NBI was rated more highly than HR-WLE for imaging quality, this did not result in improved interobserver agreement or increased yield for identifying early neoplasia in Barrett's esophagus. This applied to non-expert as well as expert endoscopists.

Aim: To investigate the correlation between ASCA and presence of mucosal S. cerevisiae DNA in a population of CD, ulcerative colitis (UC) patients and controls., Methods: S. cerevisiae-specific primers and a fluorescent probe were designed for a 5' exonuclease real time PCR (TaqMan) assay, which is a homogenous system using a fluorescent-labelled probe for the detection of PCR product in real time. We analyzed the relation of the PCR results with the ASCA findings in a group of 76 inflammatory bowel disease (IBD) patients (31 CD, 45 UC) and 22 healthy controls (HC)., Results: ASCA (IgA or IgG) were positive in 19 (61%) patients with CD, 12 (27%) with UC and none of the HC. PCR amplification was inhibited and excluded from the final results in 10 (22%) UC patients, 7 (22%) CD patients, and 6 (30%) HC. In only 15 of the mucosal samples, S. cerevisiae DNA was detected by real time PCR, including 7 (29%) in CD, 7 (19%) in UC, 1 (6%) in HC. In 4 CD and in 4 UC patients, ASCA and mucosal S. cerevisiae were positive. Mucosal S. cerevisiae was present in combination with negative ASCA IgA and IgG in 3 UC, and 3 CD patients., Conclusion: We conclude that since the presence of S. cerevisiae in colonic mucosal biopsy specimens is very rare, ASCA is unlikely to be explained by continuous exposure to S. cerevisiae in the mucosa. Therefore, ASCA formation must occur earlier in life and levels remain relatively stable thereafter in immunological susceptible persons.

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.