| Grant number: | 22/01691-6 |
| Support Opportunities: | Regular Research Grants |
| Start date: | February 01, 2023 |
| End date: | January 31, 2025 |
| Field of knowledge: | Health Sciences - Medicine - Surgery |
| Principal Investigator: | Flávio Henrique Ferreira Galvão |
| Grantee: | Flávio Henrique Ferreira Galvão |
| Host Institution: | Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated researchers: | Amadeu Batista da Silva Neto ; Juliana Barreto Salem |
Abstract
Severe fecal incontinence (SFI) is the inability to control the passage of feces through the anal canal, causing frequent and involuntary defecation, unpleasant smell, distress, reduced quality of life, perineal infections, frequent hospitalizations and complex and costly treatment. Some patients with SFI and those with cancers of the lower rectum or anal canal undergo definitive colostomy (DC), which causes psychological and economic difficulties similar to those with SFI. Its etiology includes traumatic or iatrogenic sphincter injuries, complex births, tumors, neuropathies, congenital changes, inflammatory diseases, among others. Treatment of IFG includes complex and costly surgeries that present early recurrence and high morbidity and mortality. Thus, considering that the management of SFI and DC lack effective treatment, we developed a pioneering study of anorectal transplantation in rats, where we observed graft functional recovery 15 days after transplantation and less aggressive rejection than that of small bowel transplantation. In a recent article performed by international collaboration, we observed a long evolution and good functioning in six anorectal transplants in Beagle dogs, using temporary immunosuppression with tacrolimus. As research in dogs is prohibited in Brazil, we developed an unprecedented technique of anorectal autotransplantation in swine to carry out this pre-clinical research in our environment. In the present study, we will evaluate the anorectal graft function and the rejection profile using 30 Landrace male pigs to perform 10 autotransplants (negative rejection control group) and 10 allotransplants (10 donors and 10 recipients - positive rejection group) to assess function recovery and graft rejection pattern. The animals will be observed daily regarding their clinical characteristics and every 15 days for manometric and endoscopic evaluation. On the thirtieth day after surgery or if there are serious complications, the animals will be euthanized for macroscopic evaluation of the transplant, blood collection for laboratory examination and removal of the graft for histological and immunohistochemical examination. (AU)
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