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Purpose: To determine the effects of intra-abdominal surgery on the intensities of 5 radiation-induced intestinal syndromes in survivors of pelvic cancer., Methods and Materials: The analysis included 623 women born in 1927 or later who had survived cancer. They all had received external radiation therapy toward the pelvic area to treat gynecologic cancers. Information from 344 women who did not undergo irradiation, matched for age and residency, was also included. Main outcome measures after the surgical procedures were the intensity scores for 5 radiation-induced intestinal syndromes: urgency-tenesmus syndrome, fecal-leakage syndrome, excessive mucus discharge, excessive gas discharge, and blood discharge. The scores were based on symptom frequencies obtained from patient-reported outcomes and on factor loadings obtained from a previously reported factor analysis. Follow-up was 2 to 15 years after radiation therapy., Results: Among survivors of cancer, intra-abdominal surgery increased the intensity of the urgency-tenesmus syndrome, the fecal-leakage syndrome, excessive gas discharge, and blood discharge but had a negligible effect on mucus discharge. Intra-abdominal surgery had an especially negative effect on the urgency-tenesmus syndrome. Although the combination of appendectomy with 1 or more other intra-abdominal surgeries resulted in the highest score for all syndromes, appendectomy alone had weak to no effect. In women who did not undergo irradiation, a similar pattern was seen, albeit with much lower scores., Conclusions: We found intra-abdominal surgery to be a risk factor among survivors of gynecologic cancer, increasing the intensity score of 4 out of 5 radiation-induced intestinal syndromes. During radiation therapy, it may be worthwhile to pay extra attention to the dose of unwanted ionizing radiation to the intestines if the patient previously has undergone intra-abdominal surgery., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

A deeper understanding of the radiation-induced pathophysiological processes that develop in the gut is imperative to prevent, alleviate, or eliminate cancer survivorship diseases after radiotherapy to the pelvic area. Most rodent models of high-dose gastrointestinal radiation injury are limited by high mortality. We therefore established a model that allows for the delivering of radiation in fractions at high doses while maintaining long-term survival. Adult male C57/BL6 mice were exposed to small-field irradiation, restricted to 1.5 cm of the colorectum using a linear accelerator. Each mouse received 6 or 8 Gy, two times daily in 12-h intervals in two, three, or four fractions. Acute cell death was examined at 4.5 h postirradiation and histological changes at 6 wk postirradiation. Another group was given four fractions of 8 Gy and followed over time for development of visible symptoms. Irradiation caused immediate cell death, mainly limited to the colorectum. At 6 wk postirradiation, several crypts displayed signs of radiation-induced degeneration. The degenerating crypts were seen alongside crypts that appeared perfectly healthy. Crypt survival was reduced after the fourth fraction regardless of dose, whereas the number of macrophages increased. Angiogenesis was induced, likely as a compensatory mechanism for hypoxia. Four months postirradiation, mice began to show radiation-induced symptoms, and histological examination revealed an extensive crypt loss and fibrosis. Our model is uniquely suitable for studying the long-term trajectory and underlying mechanisms of radiation-induced gastrointestinal injury. NEW & NOTEWORTHY A novel mouse model for studying the long-term trajectory of radiation-induced gut injury. The method allows for the use of high doses and multiple fractions, with minor impact on animal health for at least 3 mo. Crypt loss and a slow progression of fibrosis is observed. Crypt degeneration is a process restricted to isolated crypts. Crypt degeneration is presented as a convenient proxy endpoint for long-term radiation-induced gut injury., (Copyright © 2017 the American Physiological Society.)