Tgf-Beta1 and Igf-1 and Anastomotic Recurrence of Crohn’S Disease After Ileo-Colonic Resection
Marco Scarpa1, Marina Bortolami2, Susan L. Morgan3, Andromachi Kotsafti2, Cesare Ruffolo1, Renata D'Incà2, Eugenia Bertin1, Lino Polese1, Davide F. D'Amico1, Giacomo C. Sturniolo2, Imerio Angriman*1
1Clinica Chirurgica 1^, University of Padova, Padova, Italy; 2Gastroenterologia, University of Padua, Padua, Italy; 3Department of Pathology, Institute for Cancer Studies, Birmingham Medical School, University of Birmingham, Birmingham, United Kingdom
Background After bowel resection, Crohn’s disease (CD) recurs frequently in the site of anastomosis and “end-to-end” anastomoses are associated with a higher rate of recurrence compared to “side-to-side” ones. Alteration of normal healing processes may play a role in this phenomenon. Transforming growth factor beta (TGF-beta) and insulin-like growth factor (IGF-I) are involved in wound healing mechanisms with pro-fibrogenic properties. The aim of this study is to understand if a differential expression of reparative factors in the different zones of the bowel wall can explain why side-to-side anastomoses are associated to a lower rate of recurrence.Patients and methods Sixteen patients affected by CD who underwent ileo-colonic resection in our department, over the period 2004 to 2005, were enrolled in this study and their follow up investigated. Full-thickness tissue samples were obtained from the mesenteric side, the lateral side and the anti-mesenteric side of the ileum wall. Two samples series were collected from macroscopically diseased and healthy ileum for each patient. TGF-beta1 and IGF-1 mRNAs were quantified by absolute Real Time PCR using GAPDH as the housekeeping gene. Myeloperoxidase (MPO) activity and histological disease activity were assessed to quantify the ileal inflammation. Comparisons and correlations were carried out with nonparametric tests.Results Although no significant difference was observed between the three groups, a significant correlation between TGF-beta1 relative levels in diseased bowel and the sampling site was observed (tau=0.43, p=0.03); the closer the sampling site was to the mesenteric side the higher were TGF-beta1 relative levels. In comparison, neither IGF-1 mRNA transcripts nor MPO activity showed any relation with the sampling site. Conclusion Our study seems to suggest that TGF-beta1 mRNA expression is lower in the anti-mesenteric side of the ileum. Since we have previously demonstrated that high expression of TGF-beta1 is associated with early recurrence it seems rational to construct the anastomosis on the anti-mesenteric side of the bowel. Therefore a side-to-side anastomosis seems to be the most suitable to minimize the recurrence risk of CD.
