Abstract
BackgroundRadiation proctitis affects 1-20% of cancer patients undergoing radiation exposure due to pelvic malignancies, including prostate, gynecological and rectum cancers. The patients manifest rectal discomfort, pain, discharge, and bleeding. Notably, the efficacy of prophylactic measures remains controversial due to the lack of adequate animal models that mimic this condition.ObjectiveThe present study then aimed to develop a murine model of high-dose-rate (HDR) brachytherapy-induced proctitis.Material/MethodsC57BL/6 male mice were subjected to HDR (radiation source: iridium-192 [Ir-192]) through a cylindrical propylene tube inserted 2 cm far from the anal verge into the rectum. The animals received radiation doses once a day for three consecutive days (fractions of 9.5 Grays [Gy]), 3.0 mm far from the applicator surface. The sham group received only the applicator with no radiation source. The survival rate was recorded, and a colonoscopy was performed to confirm the tissue lesion development. Following euthanasia, samples of the rectum were collected for histopathology, cytokines dosage (IL-6 and KC), and immunohistochemical analysis (TNF-α and COX-2).ResultsHDR significantly reduced animals’ survival ten days post first radiation exposure (14% survival vs. 100% in the non-irradiated group). Day seven was then used for further investigation. Mice exposed to radiation presented with rectum injury confirmed by colonoscopy and histopathology (P < 0.05 vs. the control group). The tissue damage was accompanied by an inflammatory response, marked by increased KC and IL-6 tissue levels, and immunostaining for TNF-α and COX-2 (P < 0.05 vs. control group).ConclusionsWe established a novel animal model of actinic proctitis induced by HDR brachytherapy, marked by inflammatory damage and low animal mortality.
Highlights
Radiation proctitis is a side effect that affects cancer patients undergoing radiation exposure due to pelvic malignancies [1]
The present study aimed to develop a murine model of high-dose-rate (HDR) brachytherapy-induced proctitis
Mice exposed to radiation presented with rectum injury confirmed by colonoscopy and histopathology (P < 0.05 vs. the control group)
Summary
Radiation proctitis is a side effect that affects cancer patients undergoing radiation exposure due to pelvic malignancies [1]. Patients who develop radiation proctitis experience rectal discomfort, pain, and discharge or bleeding, with the consequent need for endoscopic interventions [1]. The efficacy of prophylactic measures, including daily intravenous use of amifostine prior to therapy [4] or sucralfate administered by topical or oral routes [5], remains controversial [1]. Clinical management of radiation proctitis comprises amifostine, mesalazine, sucralfate, formalin local application, electrocoagulation, Nd-YAG laser, and hyperbaric oxygen therapy. All these therapeutic options present poor outcomes [1, 6]. Radiation proctitis affects 1-20% of cancer patients undergoing radiation exposure due to pelvic malignancies, including prostate, gynecological and rectum cancers. The efficacy of prophylactic measures remains controversial due to the lack of adequate animal models that mimic this condition
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