Multicenter, randomized, controlled trial of confocal laser endomicroscopy assessment of residual metaplasia after mucosal ablation or resection of GI neoplasia in Barrett's esophagus.

BACKGROUND: Endoscopic ablation is an accepted standard for neoplasia in Barrett's esophagus (BE). Eradication of all glandular mucosa in the distal esophagus cannot be reliably determined at endoscopy. OBJECTIVE: To assess if use of probe-based confocal laser endomicroscopy (pCLE) in addition to high-definition white light (HDWL) could aid in determination of residual BE. DESIGN: Prospective, multicenter, randomized, clinical trial. SETTING: Academic medical centers. PATIENTS: Patients with Barrett's esophagus undergoing ablation. INTERVENTION: After an initial attempt at ablation, patients were followed-up either with HDWL endoscopy or HDWL plus pCLE, with treatment of residual metaplasia or neoplasia based on endoscopic findings and pCLE used to avoid overtreatment. MAIN OUTCOME MEASUREMENTS: The proportion of optimally treated patients, defined as those with residual BE who were treated and had complete ablation plus those without BE who were not treated and had no evidence of disease at follow-up. RESULTS: The study was halted at the planned interim analysis based on a priori criteria. After enrollment was halted, all patients who had been randomized were followed to study completion. Among the 119 patients with follow-up, there was no difference in the proportion of patients achieving optimal outcomes in the two groups (15/57, 26% for HDWL; 17/62, 27% with HDWL + pCLE). Other outcomes were similar in the two groups. LIMITATIONS: The study was closed after the interim analysis due to low conditional power resulting from lack of difference between groups as well as higher-than-expected residual Barrett's esophagus in both arms. CONCLUSION: This study yields no evidence that the addition of pCLE to HDWL imaging for detection of residual Barrett's esophagus or neoplasia can provide improved treatment.

Characterisation of early mucosal and neuronal lesions following Shigella flexneri infection in human colon.

BACKGROUND: Shigella, an enteroinvasive bacteria induces a major inflammatory response responsible for acute rectocolitis in humans. However, early effect of Shigella flexneri (S. flexneri) infection upon the human mucosa and its microenvironement, in particular the enteric nervous system, remains currently unknown. Therefore, in this study, we sought to characterize ex vivo the early events of shigellosis in a model of human colonic explants. In particular, we aimed at identifying factors produced by S. flexneri and responsible for the lesions of the barrier. We also aimed at determining the putative lesions of the enteric nervous system induced by S. flexneri. METHODOLOGY/PRINCIPAL FINDINGS: We first showed that, following 3 h of infection, the invasive but not the non-invasive strain of S. flexneri induced significant desquamation of the intestinal epithelial barrier and a reduction of epithelial height. These changes were significantly reduced following infection with SepA deficient S. flexneri strains. Secondly, S. flexneri induced rapid neuronal morphological alterations suggestive of cell death in enteric submucosal neurones. These alterations were associated with a significant increase in the proportion of vasoactive intestinal peptide (VIP) immunoreactive (IR) neurons but not in total VIP levels. The NMDA receptor antagonist MK-801 blocked neuronal morphological changes induced by S. flexneri, but not the increase in the proportion of VIP-IR. CONCLUSIONS/SIGNIFICANCE: This human explant model can be used to gain better insight into the early pathogenic events following S. flexneri infection and the mechanisms involved.