title: Sirolimus and intraoperative hyperthermic peritoneal chemoperfusion with mitomycin-C do not impair healing of bowel anastomoses.
abstract: Surgeons will increasingly have to address the development of gastrointestinal disease in transplant patients or deal with extended bowel resection and bowel anastomosis in advanced cancer patients. Immunosuppressants as well as intraoperative hyperthermic peritoneal chemoperfusion (IHPC) may alter intestinal anastomotic healing. We evaluated the effects of the immunosuppressant sirolimus and of IHPC on healing and stability of bowel anastomoses in pigs. Twenty-four pigs were divided into four groups (SIR: sirolimus was administered orally; IHPC: animals received IHPC with mitomycin-C; COMP: combination of sirolimus and IHPC was administered; CON: sham-treated control group). Animals underwent hand-sutured small bowel and left colon anastomoses and were killed on postoperative day 4. Anastomoses were evaluated by morphometric analysis and immunohistochemistry (IHC) and by measuring the bursting pressure (BP). In all experimental groups (SIR, IHPC, COMP), anastomotic BPs remained unaltered and were not statistically different compared with control (CON). In addition, ileum villous height and colonic crypt depth analysis revealed no significant difference in mucosal thickness, and IHC showed no difference among groups in proliferation, as assessed by the number of KI-67- and bromodeoxyuridine-labeled cells. Immunosuppression with sirolimus as well as IHPC with mitomycin-C do not alter healing of intestinal anastomosis in pigs.
authors.affiliation: Department of Visceral and Transplantation Surgery, University Hospital Bern, Bern, Switzerland.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Wagner
authors.forename: Roman A
authors.initials: RA
authors.lastname: Inglin
authors.forename: Sonja
authors.initials: S
authors.lastname: Bisch-Knaden
authors.forename: Daniel
authors.initials: D
authors.lastname: Mettler
authors.forename: Markus
authors.initials: M
authors.lastname: Borner
authors.forename: Daniel
authors.initials: D
authors.lastname: Candinas
authors.forename: Bernhard
authors.initials: B
authors.lastname: Egger
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D049109:Cell Proliferation / Q000187:drug effects; D004067:Digestive System Neoplasms / Q000188:drug therapy / Q000601:surgery; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007422:Intestines / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects*; D023421:Models, Animal; D010477:Perfusion; D010529:Peritoneal Cavity; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary; D020123:Sirolimus / Q000009:adverse effects*; D034421:Sus scrofa; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D016685:Mitomycin; D020123:Sirolimus