title: Early outcome of different steroid-free regimens in small bowel transplantation: a large-animal study.
abstract: The intestine is a highly immunogenic organ that requires heavy immunosuppression (IS); therefore corticosteroid withdrawal after clinical small bowel transplantation (SBT) has not been standardized. In this study, we compared different immunosuppressive regimens (none with steroid or induction treatment) in a SBT pig model. Large White unrelated piglets were transplanted and divided into four groups as follow: group 1 (n = 3): no IS; group 2 (n = 10): IS with tacrolimus only; group 3 (n = 10): IS with tacrolimus and mycophenolate mofetil; group 4 (n = 5): IS with tacrolimus and rapamycin. Follow-up time was 30 days. All IS drugs were given orally; tacrolimus whole blood levels ranged between 5 and 15 ng/mL in all groups except for group 2 whose tacrolimus whole blood levels ranged between 15 and 25 ng/mL. Group 1 pigs died of graft acute rejection (ACR) after a median of 12 days. Overall survival in groups 2, 3, and 4 at day 30 was 40%, 80%, and 60%, respectively. Biochemical parameters, including glycemia and cholesterol, were into the normal range with no significant differences between groups. At the end of the study, one animal in group 2 and another one in group 4 showed histological signs of moderate to severe ACR. The incidence of infection was higher in group 2 (2.1 episodes/pig) compared to group 3 (1.25) and group 4 (1.6). This large-animal study demonstrates that tacrolimus-based IS without corticosteroids allows, in the early postoperative period (30 days) after SBT, good survival rates without an increased risk in the incidence of rejection.
authors.affiliation: Department of Surgery, University of Pavia School of Medicine and I.R.C.C.S. Policlinico San Matteo Hospital, Piazzale Golgi 2, 27100 Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Doni
authors.forename: L
authors.initials: L
authors.lastname: Cobianchi
authors.forename: M
authors.initials: M
authors.lastname: Alessiani
authors.forename: S
authors.initials: S
authors.lastname: Zonta
authors.forename: F
authors.initials: F
authors.lastname: Abbiati
authors.forename: P
authors.initials: P
authors.lastname: Morbini
authors.forename: M
authors.initials: M
authors.lastname: Bardone
authors.forename: M
authors.initials: M
authors.lastname: Mazzilli
authors.forename: J
authors.initials: J
authors.lastname: Viganò
authors.forename: M
authors.initials: M
authors.lastname: De Martino
authors.forename: T
authors.initials: T
authors.lastname: Dominioni
authors.forename: B
authors.initials: B
authors.lastname: Dionigi
authors.forename: M D
authors.initials: MD
authors.lastname: Molinaro
authors.forename: A
authors.initials: A
authors.lastname: Bottazzi
authors.forename: P
authors.initials: P
authors.lastname: Dionigi
mesh_terms: D000305:Adrenal Cortex Hormones; D000818:Animals; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007421:Intestine, Small / Q000637:transplantation*; D023421:Models, Animal; D013552:Swine; D014184:Transplantation, Homologous / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents