Reducing colorectal anastomotic leakage with tissue adhesive in experimental inflammatory bowel disease.

Wu, Zhouqiao; Boersema, Geesien S A; Kroese, Leonard F; Taha, Diman; Vennix, Sandra; Bastiaansen-Jenniskens, Yvonne M; Lam, King H; Kleinrensink, Gert-Jan; Jeekel, Johannes; Peppelenbosch, Maikel; Lange, Johan F

BACKGROUND Anastomotic leakage after gastrointestinal surgery remains a challenging clinical problem. This study aimed to investigate the effectiveness of TissuCol (fibrin glue), Histoacryl Flex (n-butyl-2-cyanoacrylate), and Duraseal (polyethylene glycol) on colorectal anastomotic healing during experimental colitis. METHODS We first performed colectomy 7 days after 10 mg trinitrobenzene sulfonic acid (TNBS)-induced colitis to validate a rat TNBS-colitis-colectomy model. Subsequently, this TNBS-colitis-colectomy model was used in 73 Wistar rats that were stratified into a colitis group (CG, no adhesive), a TissuCol group (TG), a Histoacryl group (HG), and a Duraseal group (DG). Anastomotic sealant was applied with one adhesive after constructing an end-to-end hand-sewn anastomosis. Clinical manifestations, anastomotic bursting pressure, and immunohistochemistry of macrophage type-one (M1) and type-two (M2) was performed on postoperative day (POD)3 or POD7. RESULTS TNBS-caused mucosal and submucosal colon damage and compromised anastomotic healing (i.e., abscess formation and low anastomotic bursting pressure). On POD3, higher severity of abscesses was seen in CG. Average anastomotic bursting pressure was 53.2 ± 35.5 mm Hg in CG, which was significantly lower than HG (134.4 ± 27.5 mm Hg) and DG (95.1 ± 54.3 mm Hg) but not TG (83.4 ± 46.7 mm Hg). Furthermore, a significantly higher M2/M1 index was found in HG. On POD7, abscesses were only seen in CG (6/9) but not in other groups; HG had the lowest severity of adhesion. CONCLUSIONS We describe the first surgical IBD model by performing colectomy in rats with TNBS-induced colitis, which causes intra-abdominal abscess formation and compromises anastomotic healing. Anastomotic sealing with Histoacryl Flex prevents these complications in this model. Alternative activation of macrophages seems to be involved in its influence on anastomotic healing.