Introduction Increased intestinal permeability and endotoxaemia occur in acute pancreatitis (AP) but have yet to be confirmed in chronic pancreatitis (CP). Confocal endomicroscopy (CEM) is a novel technology that has identified epithelial gaps and leakage of intravenously administered fluorescein from small intestinal mucosa in inflammatory bowel diseases. We aimed to determine intestinal permeability changes in AP and CP using CEM, assessing associations with endotoxaemia, circulating cytokines and alterations in duodenal flora.
Method 182 patients were recruited: 35 mild AP; 11 moderate AP; 8 severe AP (Determinant Based Classification); 47 CP (27 surgically managed, 20 conservatively managed); 33 chronic liver disease and 48 non-ulcer dyspepsia (from whom 14 healthy H. pylorinegative controls were identified). Blood was sampled and duodenal fluid aspirated for culture. CEM was performed in consenting patients and fluorescein leakage scored by two independent blinded investigators. Plasma endotoxin antibodies, serum cytokine concentrations and lactulose:mannitol ratios were measured; D-amino oxidase concentrations were assayed in AP patients undergoing CEM.
Results Fluorescein leakage from epithelial villi at CEM and lactulose:mannitol ratios were significantly higher in AP patients (p = 0.0346 and p = 0.046 respectively) and surgically managed CP (p = 0.032, p = 0.030) compared to healthy controls. Patients with AP more frequently showed positive duodenal bacterial cultures than controls (p = 0.004); positive duodenal cultures were associated with fluorescein leakage (p = 0.035). Plasma IgM and IgG concentrations were decreased in AP compared to controls, most markedly in severe AP, and multiple cytokines showed significantly increased concentrations in severe AP. D-amino oxidase enzyme concentrations were significantly increased in those AP patients who showed fluorescein leakage at CEM (p = 0.035).
Conclusion CEM identified increased intestinal permeability in AP and surgically managed CP, associated with endotoxaemia, increased serum inflammatory cytokines and D-amino oxidase. These changes were most marked in severe AP. The association of fluorescein leakage with duodenal bacterial proliferation in AP indicates major gut dysfunction that may account for bacterial translocation via epithelial gaps, contributing to AP severity.
Disclosure of interest None Declared.