Radiation enteropathy—pathogenesis, treatment and prevention

Abstract

There has been only modest change in cancer incidence and mortality during the past several decades, but the number of cancer survivors has almost tripled during the same period. With an increasing cohort of cancer survivors, efforts to prevent, diagnose, and manage side effects of cancer therapy in general and, specifically those of radiation therapy have intensified. Many cancer survivors have undergone radiation therapy of tumors in the pelvis or abdomen, thus rendering the bowel at risk for injury. In fact, the current prevalence of patients with long term radiation-induced intestinal side effects exceeds that of ulcerative colitis and Crohn’s disease combined. Significant progress toward reducing toxicity of radiation therapy has been made by the introduction of so-called dose-sculpting treatment techniques, which allow more precise delivery of the radiation beam. Moreover, new insight into the underlying pathophysiology have resulted in an improved understanding of mechanisms of radiation-induced bowel toxicity and in development of new diagnostic strategies and management opportunities. This article discusses the pathogenesis of early and delayed radiation-induced bowel toxicity, reviews current management options, and outlines priorities for future research. The gastroenterologist by adding insight into molecular and cellular mechanisms of related bowel disorders can substantially strengthen these efforts.

Prevention and Management of Radiation-induced Late Gastrointestinal Toxicity

“…The RMH algorithm is summarised in a recent Nature Review article ( Figure 1) (117). An initial triage is suggested to assess whether GI symptoms need to be the only focus, or whether there are other significant issues (including, but not exclusive to, gynaecological, urological or psychological problems).…”

Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival

“…Herein, we demonstrate that mice allowed to feed ad libitum before receiving high-dose chemotherapy showed marked histological changes to SI epithelium before death. These histological changes reflected loss of regenerative capacity as a result of stem cell depletion as well as structural damage from inflammatory cell infiltrates, similar to the SI response to high-dose ionizing radiation (10). In contrast, SI homeostasis was preserved in fasted mice by protection of stem cell viability and prevention of proinflammatory cell infiltrates.…”

Pelvic radiation disease: Updates on treatment options

“…However, acute and chronic radiation toxicities are not independent events, as it is underlined by the consequential late effect theory: indeed, late injury is more likely to develop when severe acute toxicity exists [20,21] . Recent studies have added complexity to these models [17] , however a deeper discussion on the pathological basis of PRD is beyond the purpose of this review and we invite to consider for this purpose the review by Hauer-Jensen et al [17] .…”

“…It has also been demonstrated that the gut microbiota, consisting of about 100 trillion bacteria, influences radiation-induced damage [16] . Thus, the understanding of PRD pathogenesis has gone far beyond the single "target cell" concept, and considers intestinal toxicity as the result of multiple interactions between epithelial injury, gut microvasculature, enteric nervous system, and gut microbiota [17] . Acute and chronic gastrointestinal toxicity have a different pathogenesis [18] .…”