Anorectal Transplantation: The First Long-Term Success in a Canine Model

Background: Anorectal transplantation is a challenging procedure but a promising option for patients with weakened or completely absent anorectal function. We constructed a canine model of anorectal transplantation, evaluated the long-term outcomes, and controlled rejection and infection in allotransplantation. Methods: In the pudendal nerve function study, six dogs were randomly divided into two groups: transection and anastomosis, and were compared with a control using anorectal manometry, electromyography, and histological examination of the anorectal segment. In the anorectal transplantation model, four dogs were assigned to four groups: autotransplant, allotransplant with immunosuppression, allotransplant without immunosuppression, and normal control. Long-term function was evaluated by defecography, videography, and histological examination of the graft. Findings: In the pudendal nerve function study, anorectal manometry indicated that the anastomosis group recovered partial function 6 months postoperatively, but the resection group never regained function. Microscopically, the pudendal nerve and the sphincter muscle regenerated, and function was well-maintained in the anastomosis group at the end of the study. Anorectal transplantation was technically successful with a three-stage operation: colostomy preparation, anorectal transplantation, and stoma closure. The dog who underwent allotransplantation and immunosuppression had two episodes of mild rejection, which were reversed with methylprednisolone and tacrolimus. The dog who underwent allotransplantation without immunosuppression had a severe acute rejection that resulted in graft necrosis. Successful dogs had full defecation control at the end of the study. Interpretation: We described the first long-term success with anorectal transplantation in a canine model. This report is a proof-of-concept study for anorectal transplantation as a treatment for patients with an ostomy because of anorectal dysfunction. Funding Statement: This study was funded by a Japanese Society of Gastroenterology (JSPS) Fellows Grant (number: 201600159), and a JSPS KAKENHI Grant (number: JP 19K18075). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All animal experiments were approved by the Animal Experimental Committee of Kyoto University and the University of Tokyo Animal Care and use Committee.