Hyperbaric oxygen therapy as a complementary treatment for radiation proctitis: Useless or useful? - A literature review

Abstract

Radiotherapy (RT) is the backbone of multimodality treatment of more than half of cancer cases. Despite new modern RT techniques, late complications may occur such as radiation proctitis (RP). The natural history of RP is unpredictable. Minor symptoms may resolve spontaneously or require conservative treatment. On the other hand, for similar and uncomplicated clinical contexts, symptoms may persist and can even be refractory to the progressive increase in treatment measures. Over the last decades, an enormous therapeutic armamentarium has been considered in RP, including hyperbaric oxygen therapy (HBOT). Currently, the evidence regarding the impact of HBOT on RP and its benefits is conflicting. Additional prospective and randomised studies are necessary to validate HBOT's effectiveness in the 'real world' clinical practice. This article reviewed the relevant literature on pathophysiology, clinical presentation, different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT.

Keywords: Delayed radiation injury; Hyperbaric oxygen; Hyperbaric oxygen therapy; Late radiation tissue injury; Late sequelae; Radiation proctitis; Radiation proctopathy; Radio-induced lesion; Radiotherapy; Review.

Figure 1

Representative scheme of intestinal injury induced by ionising radiation. In a healthy gut, crypts are with intact mucosa. Lgr5⁺ stem cells proliferate and cells migrate upwards to provide differentiated epithelial cells of the villi. Acute lesions occur predominantly through different pathological processes: Depletion of epithelial cells due to cytotoxicity in progenitor cells and consequent apoptosis; inflammation and infiltration of the lamina propria with polymorphonuclear leukocytes and plasma cells; eosinophilic abscesses of intestinal crypts; endothelial lesions of intestinal microvascularisation with the release of thrombin and eventual oedema of the submucosa; influx of antigenic material, including gut microbiota into the lamina propria. If the submucosa modifications are not impactful, the epithelial cells regenerate, and the process resolves spontaneously. The constitutive and chronic phase comprises obliterating endarteritis with progressive reduction of parietal irrigation and consequent local ischaemia; formation and diffuse progression of mucosal and submucosal fibrosis through a local proinflammatory cytokine cascade (high levels of interleukin-1β (IL-1β), IL-2, IL-6, IL-8, and transforming growth factor-β), which is promoted by macrophages, neutrophils and by the differentiation of fibroblasts into myofibroblasts. Citation: Adapted from Costa et al[21] and Kumagai et al[23].

Figure 2

Representative scheme of the several pathophysiological mechanisms involved in radiation proctitis: The hypoxia/hypocellularity/hypovascularisation, intestinal microbiota and the fibroatrophic theories. FGFb: Basic fibroblast growth factor; IGF1: Insulin-like growth factor 1; IL: Interleukin; INF-β: Interferon- beta; PDGF: Platelet-derived growth factor; ROS: Reactive oxygen species; TGF-β1: Transforming growth factor beta-1; TNF-α: Tumour necrosis factor-alpha. Citation: Adapted from Costa DA et al[21].

Figure 3

Suggested treatment algorithm for radiation proctitis based on variables related to the patient, institution, and the severity of the clinical context. RP: Radiation proctitis; RT: Radiotherapy.