The use of single balloon enteroscopy in Crohn's disease and its impact on clinical outcome.

OBJECTIVES: Single balloon enteroscopy (SBE) is an effective and safe modality for the diagnosis and therapeutic intervention of small bowel disorders. Its use in patients with Crohn's disease (CD) and particularly its effect on management changes in CD have not yet been determined. MATERIALS AND METHODS: We performed a retrospective review of the endoscopic and clinical data available on a cohort of patients with small bowel CD who had undergone SBE to determine the diagnostic and therapeutic yield of the procedure and the initial and longer-term impact it had on clinical management. RESULTS: About 52 patients have undergone SBE in our unit for the investigation of known (n = 39) or suspected (n = 13) small bowel CD with a diagnostic yield of 77% and 39%, respectively. SBE had an immediate clinical impact in 69% (n = 33) of patients, including dilatation of a stricture in 27% (n = 13), initiation or adjustment of dose of medications in 48% (n = 23), referral for surgical resection in 6% (n = 3). Moreover, the procedure permitted determining a new diagnosis of CD in 8% of the patients (n = 4), and excluding it in 8% (n = 4). Longer term follow-up was available in 34 patients (65%) which showed a significant difference in mean HBI score from 6.6 before the procedure to 4.2 after it (p < .0001). CONCLUSIONS: SBE has a high diagnostic and therapeutic yield in CD and significantly impacts disease management. Careful patient selection is a key factor in optimizing its use in CD.

Multiparametric Evaluation Predicts Different Mid-Term Outcomes in Crohn's Disease.

AIM: To evaluate if a single and/or combined (clinical, endoscopic and radiological) assessment could predict clinical outcomes in Crohn's disease (CD). METHODS: We prospectively evaluated 57 CD cases who underwent both a colonoscopy and a CT-enterography (CTE). Harvey-Bradshaw Index (HBi), SES-CD (and/or Rutgeerts score) and the radiological disease activity were defined to stratify patients according to clinical, endoscopic and radiological disease activity respectively. Hospitalizations, surgery, therapeutic changes and deaths were evaluated up to 36 months (time 1) for 53 patients. RESULTS: CTE and endoscopy agreed in stratifying disease activity in 47% of cases (k = -0.05; p = 0.694), CTE and HBi in 35% (k = 0.09; p = 0.08), endoscopy and HBi in 39% (k = 0.13; p = 0.03). Taken together, CTE, endoscopy and HBi agreed only in 18% of cases (k = 0.01; p = 0.41). Among the 11 cases with mucosal healing, only 3 (27%) showed transmural healing. Patients with endoscopic activity needed significantly more changes of therapy compared to patients with endoscopic remission (p = 0.02). Patients with higher transmural or clinical activity at baseline required significantly more hospitalizations (p < 0.01). Hospitalization rate decreases with an increase in the number of parameters indicating remissions at baseline (p = 0.04). CONCLUSIONS: Clinical, endoscopic and radiological assessments offer complementary information and could predict different mid-term outcomes in CD.

Direct effect of infliximab on intestinal mucosa sustains mucosal healing: exploring new mechanisms of action.

BACKGROUND: Infliximab is effective in inflammatory bowel disease through several mechanisms, possibly acting at the mucosal level. AIM: To assess the role of infliximab on intestinal mucosa and whether it contributes to mucosal healing. METHODS: Human colonic mucosal biopsies were incubated with or without infliximab. Cultured biopsies were evaluated for histological staining, CD68, CD3, E-cadherin and phospho-extracellular signal-regulated kinases (ERK) expression, and apoptosis. A scratch assay and MTT assay were performed with Caco2 cells in the presence of infliximab and/or tumour necrosis factor (TNF)-α or treated with supernatants obtained from human peripheral blood mononuclear cells or human intestinal fibroblasts treated with TNF-α and infliximab alone or in association. RESULTS: Infliximab-treated biopsies displayed a better histological appearance, reduced inflammation with an increase of E-cadherin, phospho-ERK and apoptosis. Supernatants showed lower TNF-α, IL-17, IL-6 and IL-8 concentration, with an increase in fibroblast-growth-factor. Motility at scratch assay and proliferation at MTT assay of Caco2 cells displayed differential modulation by TNF-α and infliximab, directly or through supernatants of human intestinal fibroblasts and human peripheral blood mononuclear cells exposed to them. CONCLUSION: Infliximab contributes to the mucosal healing process by acting directly at an intestinal mucosal level; infliximab indirectly affects epithelial cell migration and proliferation by acting on both fibroblasts and leukocytes.

Locally injected Infliximab ameliorates murine DSS colitis: differences in serum and intestinal levels of drug between healthy and colitic mice.

BACKGROUND: Infliximab is effective in human and murine IBD, but its pharmacodynamic is still poorly known. The aim of this study was to assess the affinity of infliximab to murine TNF-α, its role in murine colitis when administered intra-rectally and its levels in the blood, gut mucosa and stool of healthy and sick mice. METHODS: An ELISA kit was built in order to assess the affinity of infliximab to human or murine-TNF-α. Human IgG were used as controls. DSS model of colitis on C57BL/6 mice was used to assess clinical efficacy of infliximab administered intravenously or by enema. Stool, serum and colon samples were collected to assess infliximab levels and histology for Rachmilewitz score. RESULTS: Infliximab showed a good affinity both for human-TNF-α and murine-TNF-α. In DSS colitic mice infliximab ameliorated the severity of colitis, regardless of the administration route. In comparison with colitic mice, healthy mice displayed higher serum and mucosal infliximab levels, while detectable levels of infliximab were found in faeces, particularly in colitic mice. CONCLUSION: Our data support murine models to study infliximab pharmacokinetics and dynamics. Measurable levels of infliximab can be found at different concentrations in blood, intestinal mucosa and stool from healthy and sick mice, thus infliximab pharmacokinetics could have a major impact in human IBD.