Changes in the gastrointestinal mucosa after radio- and chemotherapy of the neoplasms Review article

Abstract

Gastrointestinal mucositis induced by radio- and chemotherapy of the neoplasms is associated with morphological changes in the mucosa of the alimentary tract. The pain, ulceration, nausea, vomiting and diarrhea are the effect of the damage of the mucus secretion, decreased goblet cells and changes in the microflora of the mucosa. Over the last years, investigators defined the basic molecular mechanisms of the mucosal barrier injury. Sonis et al. presented the model of the five phases: initiation, upregulation with generation of messengers, signaling and amplification, ulceration with inflammation and healing. The toxic agent (radiation and chemotherapy) play a key role in the described model of mucositis. The liberating reactive oxygen species (ROS) start a cascade of events. ROS directly damage cells, tissues and blood vessels. In subsequent phases plays a crucial role a nuclear factor κB (NF-κB) and increased local production of proinflammatory cytokines IL-1β, IL-6 and Tumor Necrosis Factor (TNF). Then the role of COX-2 is a hallmark in the initiation of inflammation and activation of matrix metaloproteina. In an earlier stage a damage of the submucosa, and next a injury of mucosa are observed. From a clinical point of view, it is important to stage ulcers due to the penetration of bacteria to the small blood vessels leading to sepsis. Healing phase after 2 to 4 weeks, the severity of the changes after radiation or chemotherapy. Clinical symptoms and morphological changes caused by radiation and chemotherapy for cancer are at an early split in the form of acute radiation- induced reactions produced up to 3−6 months. The symptoms are chronic late after radiation reaction of subacute phase up to 1 year, chronic phase of 1 year to 5 years and over the distant phase of 5 years from the activation of toxic factors. Complication of acute reaction after irradiation is followed by necrosis, ulceration and perforation of the intestinal wall. In the subacute phase states telangiectasia in the mucosa and submucosa, vascular diameter is larger than the light crypts. Changes include the vascular wall, which is visible proliferation and fibrosis of the inner lining, medial, and glazing are visible endothelial cells as foamy cells. In the chronic phase and can occur distant hyalinization of the intestinal wall. Complications are ulcers and fistulas, rectovaginal and vesicovaginal fistulae. In conclusion we can say that a better understanding of the pathophysiology of mucositis after radio-chemotherapy of tumors may contribute to the use of targeted therapy at the molecular level.