With the progress of radiotherapy technology. Radiotherapy has become an important method for the comprehensive treatment of many malignant tumors, and the incidence of radiation injury has gradually increased in recent years. Radiation enteritis (RE) is a common injury after radiotherapy for pelvic abdominal cavity and retroperitoneal malignancies. It can occur in any segment of the intestine, and the clinical manifestations are recurrent abdominal pain, diarrhea, mucus and blood stools, and even intestinal obstruction, intestinal perforation and intestinal fistula in severe cases. The incidence of radiation enteritis in patients who have received radiotherapy for pelvic tumors can be as high as 20%. How to prevent the occurrence of radiation enteritis in radiotherapy is a clinical priority. Once the symptoms appear, there is still a lack of uniform strategy.
1.Prevention of radiotherapy
1.1 Radiotherapy technology
With the continuous development of radiotherapy technology. In recent years, on the basis of three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) has been gradually developed. Whether in the target area conformality or in the protection of normal tissues have obvious advantages over three-dimensional conformal radiotherapy, this technology can maximize the protection of normal organs, improve the efficacy of radiotherapy and reduce radiotherapy damage. In the United Kingdom, 8l% of medical centers have adopted IMRT technology.
1.2 Radiotherapy positions
The incidence of intestinal injury during pelvic and abdominal radiotherapy is closely related to the volume of irradiated intestine receiving different doses. It has been suggested that changes in the patient’s position during radiotherapy can directly affect the size of the irradiated bowel volume. In turn, it may affect the incidence of acute radiation reaction and late radiation injury in the intestine. The application of special radiotherapy immobilization devices and change of radiotherapy position to reduce the irradiated volume of the intestine can be an effective measure to reduce intestinal radiotherapy injury.
1.3 Duration of radiotherapy
Animal studies have shown that when rats are treated with radiotherapy at different times of the day. The number of apoptotic cells in the intestinal crypt also showed a certain diurnal pattern. Based on such research, some scholars have proposed the concept of chronological radiotherapy, i.e., choosing the best time for radiotherapy to reduce radiation damage. The circadian pattern of radiotherapy can directly affect the mucosal response of small intestine. The radiation damage to the intestine can be reduced by adjusting the timing of radiotherapy. However, in practice, the strict limitation of radiotherapy time period is difficult to be fully realized in large radiotherapy centers.
2.Prevention and treatment of drugs
2.1 Intestinal probiotic preparation
Probiotics are live bacterial preparations that act directly or indirectly on the intestinal epithelium, which can improve intestinal flora, enhance intestinal barrier function and regulate the immune system, and relieve diarrhea and other symptoms. Some researchers believe that dysbiosis of the intestinal flora may be a factor in the development of radiation enteropathy. Starting prophylactic oral probiotics before the start of radiotherapy can effectively reduce the occurrence of diarrhea during radiotherapy in patients. Intestinal probiotics are easy to take. It has good prospects in the prevention and treatment of radiation enteritis.
2.2 Radioprotective agents
Amphotericin is a radioprotective agent of great interest at present. It is an organic phosphorothioate compound that is dephosphorylated in vivo to the metabolite WR-1065, which can scavenge the oxygen radicals caused by radiotherapy and thus play a protective role. Because the concentration of amphotericin in normal tissue cells is higher than that in tumor cells, it can achieve the effect of protecting normal tissues without affecting the therapeutic effect. The preventive effect of amphotericin on acute radiation enteritis is relatively clear. However, the effect on chronic radiation enteritis is still unclear, and a large randomized controlled study is still needed.
2.3 Aminosalicylates
Aminosalicylate is a compound rich in 5-aminosalicylic acid (5-ASA). Among them, 5-AsA exerts local mucosal anti-inflammatory effects in the intestine. In recent years, the role of aminosalicylates in the treatment of acute radiation enteritis has been gradually studied. The following two kinds of drugs are commonly used: ①Sulfasalazine: absorbed by the body and decomposed into 5-AsA and sulfasalazine under the action of intestinal microorganisms. A number of clinical studies have confirmed that oral administration of sulfasalazine during radiotherapy can reduce the occurrence of acute radiation enteritis. Therefore, the International Society of Oral Oncology (MASCC) recommends that oral administration of sulfasalazine twice daily during pelvic radiotherapy can reduce the incidence and severity of radiation enteritis. ②Balsalazide: 5-ASA and 4-aminobenzoyl-B-alanine are released by the action of colonic microorganisms after oral administration. Balsalazide is effective in reducing the incidence of rectosigmoiditis in radiotherapy patients. Both of these drugs have preventive effects on acute radiation intestinal injury, but there is a lack of relevant studies on whether they are effective in chronic radiation enteritis.
2.4 Intestinal mucosal protective agents
There are various intestinal mucosal protective agents. Montmorillonite preparations are derived from natural montmorillonite and are often used in intestinal disorders. Montelukast promotes the repair of intestinal mucosal epithelial cells and reduces the damage of intestinal epithelial cells caused by radiotherapy. It regulates intestinal flora, improves local immunity of the intestine and has a hemostatic effect. Another drug is aluminum thioglycollate, whose mechanism is to form a protective film on the surface of intestinal mucosa and promote intestinal mucosal angiogenesis thus promoting intestinal mucosal healing.
2.5 Glutamine
Glutamine is an essential nutrient for intestinal mucosal cell metabolism and an important energy substance for the growth, proliferation and differentiation of intestinal epithelial cells. It can maintain the integrity of intestinal mucosal epithelial structure. When the body lacks glutamine, it will cause intestinal mucosa atrophy, increase permeability, and impair intestinal immune function.
2.6 Growth inhibitors
In the application of radiation enteritis, growth inhibitors reduce the load on the intestine by reducing the secretion and loss of digestive juices, maintaining endostasis, reducing the local inflammatory response, accelerating tissue healing, and also have significant effects on bleeding, intestinal fistula, diarrhea, and intestinal obstruction caused by radiation enteritis. Growth inhibitor has better therapeutic effect than preventive effect for radiation enteritis.
2.7 Flavopiridol
The active ingredient of safranin is berberine, and a lot of clinical studies have proved that safranin can inhibit a variety of pathogenic microorganisms, and animal experiments have found that it also has the effect of antagonizing smooth muscle cell channels and relieving abdominal pain by inhibiting calcium inward flow and relaxing intestinal smooth muscle.
3.Nutritional support therapy
Nutritional support is very important in the treatment of radiation enteritis. It can be divided into parenteral nutrition and enteral nutrition. When there is severe diarrhea, gastrointestinal bleeding, intestinal obstruction, intestinal fistula and other symptoms. It is often necessary to fast and adequate parenteral nutrition support, which is conducive to intestinal recovery and at the same time can provide patients with the necessary energy needs. However, long-term fasting and parenteral nutrition also have certain disadvantages, which can make the intestinal mucosa atrophy and thus destroy the intestinal mucosal barrier function, and can also cause liver dysfunction. Therefore, when the patient’s intestinal symptoms are improved, the transition to enteral nutrition should be timely. This will help the intestine to recover its physiological function as soon as possible. In patients with radiation enteritis combined with intestinal obstruction, protein and energy malnutrition is very common. Improving the preoperative nutritional status of these patients is an important part of reducing the risk of surgery, and perioperative nutritional support plays an extremely important role in reducing postoperative complications of radiation enteritis and improving the success rate of surgery.
4.Hyperbaric oxygen therapy
Hyperbaric oxygen has a good effect on radiation intestinal injury. The mechanism of action is to stimulate the angiogenesis of the local radiation injury area, increase the oxygen supply to the intestine in this area, thus promoting the recovery of the injured tissue. Patients with intestinal injury after pelvic radiotherapy have been treated with hyperbaric oxygen. Clinical symptoms such as post-rash, rectal bleeding and ulcers have been significantly improved.
5.Stem cell transplantation
Mesenchymal stem ceUs (MSCs) are adult stem cells with strong self-replication ability and multi-directional differentiation potential, and also have immunomodulatory functions. In recent years, scholars have reported that transplantation of autologous or allogeneic MSCs is safe and effective for the treatment of inflammatory bowel disease.
6.Chinese herbal medicine treatment
Radiation enteritis belongs to the category of “diarrhea”, “dysentery” and “abdominal pain” in traditional Chinese medicine, which believes that radiation is a kind of heat poison, and radiation exposure easily depletes fluid, damages qi and blood, and injures internal organs. In the early stage of the disease, the actual evidence is the main cause, and in the long run, there is a deficiency of both qi and blood, and eventually there is a deficiency of both spleen and kidney. In addition, tumor patients have deficiency of vital energy, yin deficiency, heat toxicity, stasis and toxicity, so the disease mechanism is always a deficiency of the root and the symptoms, mixed with deficiency and reality. The main treatment is to support the positive and eliminate the evil, and to treat the symptoms in an urgent manner. The main treatment methods include Chinese medicine, acupuncture and moxibustion, Chinese medicine enema, etc.
7. Conclusion
The incidence of radiation enteritis has been on the rise in recent years, and once the symptoms appear, the progress of tumor treatment and the quality of life of patients are seriously affected. In recent years, the preventive measures for this disease have been gradually paid attention to. In radiotherapy technology, the promotion of IMRT and the change of radiotherapy device position can effectively reduce the intestinal radiation damage. At the same time, the prophylactic use of appropriate drugs to protect the intestinal damage during radiotherapy has also achieved certain results. However, there is no unified strategy for the treatment of this disease, and comprehensive treatment is still adopted. Therefore, how to standardize the treatment and how to reduce the occurrence of serious complications need to be further explored in the future.