Effect of thalidomide on the healing of colonic anastomosis, in rats / Efeito da talidomida na cicatrização de anastomoses colônicas em ratos

PURPOSE: Thalidomide, because of its anti-inflammatory properties, as re-emerged as an option for the treatment of Crohn's disease refractory to standard therapy. We studied the effect of thalidomide on the healing of colonic anastomosis. METHODS: Sixty male rats (Rattus norvegicus), were divided into 3 groups of 20 animals each, respectively receiving 0.5 or 1.0 mg/kg thalidomide by the oral route for 7 days, or saline solution (control). All animals were submitted to continuous end-to-end anastomosis with 6-0 Prolene sutures. After sacrifice the anastomoses were analyzed macroscopically and submitted to determination of hydroxyproline, to histology and to immunohistochemistry for metalloproteinase 1, metalloproteinase 1 inhibitor and vascular endothelial growth factor (VEGF). RESULTS: Statistical analysis of the data showed no significant difference in macroscopic aspect or hydroxyproline determination (p= 0.5403). In the immunohistochemical analysis, the following p values were obtained: p = 0.5817 for VEGF, p = 0.1854 for metalloproteinase 1, and p = 0.0023 for metalloproteinase 1 inhibitor, with this last value being considered statistically significant. CONCLUSION: We conclude that thalidomide influenced collagen maturation. There was a stronger action of metalloproteinases, possibly indicating a negative tendency for the healing process.

OBJETIVO: Sabe-se que agentes farmacológicos podem influenciar no processo de cicatrização. A talidomida, devido às suas propriedades antiinflamatórias, tem ressurgido como uma opção no tratamento da doença de Crõhn refratária à terapêutica convencional. Neste trabalho, estudamos o efeito da talidomida na cicatrização de anastomoses colônicas no rato. MÉTODOS: Foram utilizados 60 animais Rattus norvegius, com peso médio de 300g. Organizou-se 3 grupos de 20 animais, sendo um grupo controle (AC), um grupo (BD), com administração de talidomida 0,5 mg/kg por 7 dias e um grupo (AD) com administração de talidomida 1,0 mg/kg por 7 dias. Foi realizada anastomose término-terminal contínua de prolene 6-0. O sacrifício foi no 7º. dia pós operatório e as anastomoses foram analisadas quanto a aspecto macroscópico, dosagem de hidroxiprolina, histologia em hematoxilina-eosina e imuno-histoquímica para metaloproteinase 1, inibidor de metaloproteinase 1 e VEGF. RESULTADOS: Não houve diferença estatisticamente significante para a observação macroscópica e para dosagem de hidroxiprolina (p=0,5403). Na análise imunohistoquímica, para VEGF houve p=0,5817, para metaloproteinase 1, p=0,1854 e para inibidor de metaloproteinase, p=0,0023, considerado estatisticamente significante. CONCLUSÃO: Concluímos que a talidomida influenciou na maturação do colágeno. Notou-se maior ação das metaloproteinases, que pode significar uma tendência negativa para o processo cicatricial.

The Significance of Diverting Ileostomy during Restorative Proctocolectomy

PURPOSE: Restorative proctocolectomy (RP) is a standard surgery in patients with ulcerative colitis and familial adenomatous polyposis. Usually, diverting ileostomy is performed to protect an ileoanal anastomosis with RP. However, there are many controversies whether diverting ileostomy might urgently be needed. This study was performed to compare postoperative complications after RP with or without diverting ileostomy. METHODS: Between July 1994 and June 2001, 77 (M : F= 45 : 32) patients underwent RP. The indication criteria for diverting ileostomy included tension at the anastomosis, positive leakage test, compromised blood flow in the ileal pouch, long-term and high-dose steroid use, and severe rectal inflammation in ulcerative colitis patients. RESULTS: Histopathologic diagnoses revealed 45 ulcerative colitis, 23 familial adenomatous polyposis, 5 rectal cancer, and 4 hereditary nonpolyposis colorectal cancer. Diverting ileostomies were performed in 40 patients (51.9%) and closed approximately 4 months later. Fourty eight complications were present in 32 patients. There was no perioperative death. There was no difference in perioperative outcome, morbidity or functional status between patients with and without ileostomy. However, in ulcerative colitis patients, anastomosis leakage was more frequent in patients without ileostomy. CONCLUSIONS: Restorative proctocolectomy can be safely performed without diverting ileostomy in most cases of RP. However, diverting ileostomy may reduce anastomosis leakage in patients with ulcerative colitis.