Adhesion formation in experimental chronic radiation enteropathy

We have studied the late changes associated with radiation enteropathy in mice over a period of 224 days following single or split doses of gamma radiation delivered to the total abdomen (TAI). We focused on the importance of adhesion formation as a cause of strictures and gut-associated deaths following TAI. Gut-associated peritoneal adhesions were found in mice 2-7 months after receiving 13.5-17.5 Gy TAI and appeared to constitute the most consistent serious late effect of irradiation. There was a good correlation between adhesion formation and death for both the single and split-doses of radiation. Adhesions primarily involved the large gut, normally near the cecum. They appeared to result from serosal breakdown and were the major cause of partial gut obstruction. Submucosal fibrosis was present but seemed to be a comparatively minor cause of strictures. Local lymphoid hyperreactivity was also seen following TAI and may have contributed to the late sequelae. The complexity of the pathogenesis of chronic radiation enteropathy was indicated by finding three successive waves of non-scheduled deaths following TAI. The first wave (28-70 days) was not related to adhesion formation and may have been due to localized failure of mucosa to regenerate after irradiation with consequent ulceration. The second wave (98-140 days) occurred over the period when adhesion formation and fibrosis were most marked. In the third wave (168-224 days), the additional complication of fluid exudation was seen. Further experimentation is obviously needed to better define the complex pathogenesis of radiation enteropathy with dose and time after radiation but our data strongly support a multifactorial causation with an important role for adhesion formation in the disease complex.