Significance of overall treatment time for the development of radiation-induced intestinal complications. An experimental study in the rat.

Abstract

Late normal tissue reactions generally are believed to be independent of treatment time. However, previous studies suggest a relationship between acute mucosal injury and development of intestinal obstruction and enterocutaneous fistula formation. Thus, the pathogenesis of late intestinal complications may be complex, and mucosal cell proliferation during treatment may be important. This study assessed the influence of overall radiation treatment time on development of intestinal injury and complications after localized fractionated irradiation of rat ilium. Ninety-four male rats underwent orchiectomy, and a loop of small intestine was transposed to the scrotum. Orthovoltage irradiation was administered to the transposed, but functionally intact, intestine using 9 fractions of 5.6 Gy with interfraction intervals of 24, 48, or 72 hours. The animals were observed for complications and killed in groups 2 and 26 weeks after irradiation for assessment of injury. Incidence of intestinal complications and quantitative and semiquantitative histopathologic assessment of injury were used as endpoints. Increasing total treatment time by extending interfraction intervals from 24 to 48 hours significantly reduced radiation injury and the incidence of intestinal complications. Differences in mucosal and fibrotic changes were most prominent. No significant differences were found between groups with interfraction intervals of 48 and 72 hours. Overall treatment time significantly influenced development of chronic radiation enteropathy. Thus, rapidly proliferating cells, as found in the intestinal mucosa, appear to be involved in the pathogenesis of intestinal complications. This probably represents consequential damage secondary to disruption of mucosal integrity.