Effects of Two Conventional Preoperative Radiation Schedules on Anastomotic Healing in the Rat Colon

Abstract

Background: Preoperative radiotherapy (RT) is an increasingly popular form of adjunct therapy for rectal cancer; however, little is known about its effects on matrix metalloproteinase (MMP) expression in colonic anastomotic healing. Methods: Wistar rats were irradiated to a total dose of 25 or 40 Gy. Four days after the end of RT, an end-to-end colorectal anastomosis was performed. Animals were sacrificed at 1, 3, and 7 days after the anastomosis. A control group was studied similarly, but was not irradiated. Results: No significant differences were found in peritonitis rate and anastomotic complications. The average bursting pressure and breaking strength were only reduced significantly in the rats irradiated with 40 Gy. However, the concentration and the content of hydroxyproline in anastomotic tissues were unchanged. In irradiated rats, MMP-2 and MMP-9 were significantly increased at 40 Gy, but not at 25 Gy. On the other hand, 25-Gy irradiation induced a smaller increase in the levels of the tissue inhibitors of metalloproteinase-1 compared with the controls. Conclusion: Anastomotic strength is adversely affected by high-dose fractionated preoperative RT. In contrast, preoperative RT at 25 Gy in five fractions over 5 days is safe with regard to the maintenance of wound strength in colorectal anastomosis.

Effects of Nuclear Factor-κB Inhibitors on Colon Anastomotic Healing in Rats

“…Although sensitive, this method is time-consuming, lacks specificity, and is only semiquantitative. Our previous studies revealed that by using the activity assay systems, we were able to measure MMP-2 and MMP-9 in samples from rat tissue supernatants [23,24]. Whereas on postoperative d 3 there were no differences between the groups, we found a significant increase in MMP-2 and MMP-9 expression in control animals on d 5 after surgery.…”

Preoperative irradiation with 5 × 5 Gy in a murine isolated colon loop model does not cause anastomotic weakening after colon resection

“…Nevertheless, in most of the animal studies, the irradiation protocols were not comparable or even completely different from the clinical situation. In studies simulating clinical protocols with respect to fractionation of preoperative radiation doses [11,13,14] and irradiation of one or both limbs of the anastomosis [15], the irradiation technique appeared to be a major challenge. The murine colon is difficult to irradiate without considerable damage to surrounding tissue.…”

“…The murine colon is difficult to irradiate without considerable damage to surrounding tissue. In these studies, the colon was irradiated in situ by placing radiopaque markers and dosimeters during a laparotomy [13,15] or by irradiation of the entire pelvis which resulted in high mortality [11,14].…”

Rana catesbeiana, pólvora e modulação supramolecular cicatrização intestinal e prognóstico no câncer de cólon: uma mesma origem biológica para o insucesso?

“…Em outro estudo, calculou-se a dose de risco para a anastomose em animais, sendo observado que uma dose pré-operatória de 40Gy aumentava a expressão MMP de forma a comprometer a resistência mecânica da anastomose, ao contrário da dose 25Gy que não mostrou o mesmo efeito. (42) São muitas as estratégias no sentido de assegurar as condições à boa cicatrização do cólon. Novos materiais de sutura, associação de adesivos biológicos, técnicas para reduzir os efeitos da menor perfusão arterial, terapias farmacológicas e, até, a aplicação de agentes exógenos que promovem a angiogênese, vêm interessando um grande número de pesquisadores.…”