| disease | Radiation Enteritis |
| alias | Radiation Enteritis |
Radiation enteritis is an intestinal complication caused by radiation therapy for malignant tumors in the pelvic, abdominal, or retroperitoneal regions. It can affect the small intestine, colon, and rectum, hence also referred to as radiation proctitis, colitis, or enteritis. Depending on the radiation dose, duration, and onset speed, radiation-induced intestinal disease is generally classified into acute and chronic types. Based on the location of the radiation source, it can also be divided into external radiation sickness and internal radiation sickness. In the early stages, the renewal of intestinal mucosal cells is inhibited, followed by swelling and occlusion of small blood vessels, leading to intestinal wall ischemia and mucosal erosion. In advanced stages, fibrosis of the intestinal wall occurs, resulting in stenosis or perforation, as well as abscesses, fistulas, and intestinal adhesions in the abdominal cavity.
bubble_chart Epidemiology
Application of 60Co, ultra-high-voltage X-ray external irradiation or Ra internal irradiation, when the exposure dose exceeds 5000 rad (rad) within 5 weeks, about 8% of patients develop radiation enteritis. The reported incidence ranges from 2.4% to 2.5%. The minimum exposure dose causing intestinal radiation injury varies greatly and is mainly related to the following factors: ① The intensity and duration of irradiation. ② Adhesions or fixed intestinal segments in the abdominal or pelvic cavity are more susceptible to radiation injury. ③ After uterus removal, the rectum receives a higher radiation dose compared to when the uterus is intact, making radiation proctitis more likely. ④ The radiation tolerance of different intestinal segments, in descending order, is: rectum, sigmoid colon, transverse colon, ileum, jejunum, and duodenum. Since cervical and bladder malignancies often require radiotherapy, and the anterior wall of the rectum is adjacent to the cervix or bladder, radiation proctitis is the most common, with an incidence of 10–60%. The distal ileum is close to pelvic organs and relatively fixed in position, making it susceptible to pelvic irradiation injury.
The unit of radiation (ionizing radiation) is GY (Gray), where 1GY equals 100 rad, defined as the dose absorbed when 1 kg of tissue absorbs 1 J (Joule) of energy. cGY is the unit of radiation dose absorbed by tissue. 1 cGY is equivalent to 1 rad.(1) Inhibition of intestinal epithelial cell proliferation: The epithelial cells of the intestinal mucosa are the most sensitive to radiation. Observations using tritium-labeled thymidine to track cell renewal have shown that the renewal of the intestinal mucosa is achieved through the proliferation of undifferentiated cells located in the crypts of the intestinal glands. These cells lose their ability to divide after differentiation and gradually migrate toward the surface of the intestinal mucosa. Radiation inhibits the proliferation of these cells, leading to characteristic acute sexually transmitted disease changes in the intestinal mucosa. If the radiation dose is not excessive, mucosal injury can recover within 1–2 weeks after cessation of radiotherapy. Recent studies have found that the effects of multiple irradiations depend on the cell cycle phase of the crypt cells at the time of irradiation. Cells in the late stage [third stage] of division are most sensitive to radiation, while those in the advanced stage of synthesis exhibit stronger resistance. Since only a fraction of proliferating crypt cells are in any specific phase of the cell cycle at any given time, a single high-dose irradiation kills only a portion of the cells, and mitotic activity returns to normal within a few days.
(2) Damage to the submucosal small stirred pulse: The endothelial cells of the small stirred pulse are highly sensitive to radiation. High-dose radiotherapy causes swelling of eyelid, proliferation, and fibrinoid degeneration, leading to obliterative stirred pulse internal membraneitis and venous internal membraneitis, thereby resulting in intestinal wall ischemia, mucosal erosion, and ulcer. Further progression of the lesions occurs due to bacterial invasion from the intestinal tract.
(3) Damage to the intestinal wall tissue: Extensive and prolonged irradiation of the intestinal wall leads to edema, fibroblast proliferation in all layers of the intestinal wall, and hyaline changes in connective tissue and smooth muscle, ultimately resulting in fibrosis, intestinal stricture, distortion of the mucosal surface, and fragmentation. Thus, radiation-induced intestinal changes can range from reversible mucosal structural alterations to chronic fibrotic thickening, ulcerated intestines, and even intestinal obstruction.bubble_chart Pathological Changes
(1) Acute phase; Acute pathological changes can occur during or immediately after radiation exposure, characterized by degeneration and shedding of epithelial cells, reduced mitosis of crypt cells, thinning of the intestinal mucosa, shortening of villi, dilation of capillaries, congestion and edema of the intestinal wall mucosa, and infiltration of inflammatory cells. In the affected rectum, goblet cell hypertrophy, glandular hyperplasia, deformation, and crypt abscesses formed by acute inflammatory cells, eosinophils, and shed mucosal epithelial cells are often observed. The condition typically peaks within weeks and then subsides. If the radiation dose is large and prolonged, the mucosa may develop localized or diffuse ulcers, varying in distribution and depth, with the surrounding mucosa often showing nodular elevation and dilation of peripheral capillaries. Mucosal lesions are prone to bleeding.
(2) Subacute phase: This phase begins 2 to 12 months after radiation exposure. The mucosa shows varying degrees of regeneration and healing, but the endothelial cells of submucosal small vessels swell and detach from their basement membrane, eventually undergoing vacuolar degeneration and shedding, leading to obliterative vasculitis. A large number of distinctive "foamy macrophages" appear beneath the vascular intima, which is diagnostically significant for vascular radiation injury. Vascular occlusion results in progressive ischemia of the intestinal wall, accompanied by submucosal fibrosis with abundant fibroblasts and hyaline degeneration of smooth muscle, along with reduced collagen content. Despite this, local blood supply may still suffice, but patients may concurrently suffer from hypertension, diabetes, coronary heart disease, or vascular sclerosis. If heart failure occurs simultaneously, severe blood supply insufficiency in the intestinal wall can lead to rectal ulcers, abscesses, and the formation of rectovaginal or rectovesical fistulas.
(3) Chronic phase: Chronic lesions are essentially delayed injuries caused by latent vascular occlusion. The degree of intestinal wall ischemia varies, and chronic changes persist for an extended period. The duration between the onset of symptoms and the appearance of lesions varies, generally occurring 1 to 5 years after radiotherapy, with small intestine lesions potentially appearing up to 6.5 years post-radiation. Chronic rectal damage may manifest as late as 10 years after radiotherapy. The affected intestinal segments exhibit mucosal erosion, stubborn perforations or fistula formation, and complications such as intestinal obstruction, peritonitis, and intra-abdominal abscesses. In severe cases of small intestine lesions, mucosal villi atrophy, leading to malabsorption. In addition to ulcers and erosion, chronic rectal changes may involve significant hyperplasia of residual glandular goblet cells, causing mucus and bloody stools. Advanced stages may rarely progress to malignancy.bubble_chart Clinical Manifestations
The clinical symptoms of radiation enteritis generally occur when the total radiation dose exceeds 3000 rad, with rare cases below this threshold. Symptoms typically appear when the total intra-abdominal radiation dose exceeds 4000 rad, and the incidence rate can reach as high as 36% when the dose surpasses 7000 rad. Symptoms may manifest during the early stages of treatment, shortly after completion of the therapy, or even months to years post-treatment.
(1) Early symptoms: Due to the nervous system's response to radiation, gastrointestinal symptoms can appear early, usually within 1–2 weeks after the initiation of radiotherapy. These include nausea, vomiting, diarrhea, and the passage of mucus or bloody stools. Involvement of the rectum may be accompanied by tenesmus. Persistent hematochezia can lead to iron-deficiency anemia. Constipation is uncommon, and occasional low-grade fever may occur. Cramping abdominal pain suggests small intestine involvement. Sigmoidoscopy may reveal mucosal edema, congestion, and in severe cases, erosions or ulcers.
(2) Advanced-stage symptoms: Persistent symptoms from the acute phase or the emergence of significant symptoms 6 months to several years after radiotherapy indicates disease progression, ultimately leading to fibrosis or stenosis. Symptoms during this stage may appear as early as 6 months post-radiotherapy or as late as 10 to 30 years later, often associated with intestinal vascular inflammation and subsequent complications.
1. Colitis and proctitis: These often occur 6–18 months after irradiation. Domestic reports indicate an incidence rate of 2.7%–20.1%. Symptoms include diarrhea, hematochezia, mucus stools, tenesmus, narrowing of stools, progressive constipation, or abdominal pain, suggesting intestinal stenosis. Severe lesions may lead to fistula formation with adjacent organs, such as rectovaginal fistulas (with feces passing through the vagina), rectovesical fistulas (resulting in pneumaturia), or recto-small intestinal fistulas (with chyme mixed in stools). Intestinal perforation may cause peritonitis, abdominal or pelvic abscesses. Intestinal obstruction may occur due to stenosis and looping of the intestines. Radiation-induced rectal injuries can be classified into four grades: Grade I: Mild or no symptoms, with only Grade I mucosal edema, which typically resolves quickly. These changes are generally considered radiation-reactive injuries. Grade II: Frequent bowel movements, bloody or mucus stools, and tenesmus, which may persist for months or years. The mucosa shows necrosis, ulcers, or Grade II stenosis. Grade III: Severe rectal stenosis requiring colostomy. Grade IV: Accompanied by fistula formation. Some scholars classify radiation enteritis into four types: catarrhal, erosive-desquamative, infiltrative-ulcerative, and infiltrative-ulcerative with rectovaginal fistula. Complications of radiation enteritis include colorectal cancer, rectal adenocarcinoma, deep cystic colitis, and solitary rectal ulcers (mostly on the anterior wall, though posterior cases also occur).
2. Small intestine inflammation: Severe radiation injury to the small intestine may cause intense abdominal pain, nausea, vomiting, abdominal distension, and bloody diarrhea. However, advanced-stage manifestations primarily involve malabsorption, accompanied by intermittent abdominal pain, steatorrhea, weight loss, fatigue, and anemia.
bubble_chart Auxiliary Examination
(1) Digital rectal examination: In the early stages or mild cases of radiation enteritis, the digital rectal examination may reveal no specific findings. There may only be spasms of the anal sphincter and tenderness. In some cases, the anterior rectal wall may exhibit edema, thickening, hardening, or blood on the examination glove. Occasionally, ulcers, strictures, or fistulas may be palpated, with 3% of severe rectal injuries leading to rectovaginal fistulas. Concurrent vaginal examination can aid in diagnosis.
(2) Endoscopic examination: In the initial weeks, mucosal congestion, edema, granular changes, and increased fragility may be observed, with easy bleeding upon contact, particularly on the anterior rectal wall. Later findings include thickening, hardening, characteristic telangiectasia, ulcers, and luminal narrowing. Ulcers may appear patchy or punched-out, varying in size, and are often located on the anterior rectal wall at the level of the cervix. Rectal strictures are typically found 8–12 cm above the anal verge. Some colonic lesions resemble ulcerative colitis. Thickened, hardened mucosa and annular strictures or punched-out ulcers with firm margins, if lacking prominent surrounding telangiectasia, may be mistaken for carcinoma. Tissue biopsy can aid diagnosis but carries a risk of perforation and should be performed cautiously.
(3) X-ray examination: Barium contrast studies of the intestines help determine the extent and nature of lesions, though the findings are nonspecific. Barium enema may reveal fine serrated mucosal margins, irregular folds, rigid or spastic bowel walls. Occasionally, segmental narrowing, ulcers, and fistulas are visible. In rare cases, the mucosa around ulcers may appear elevated, mimicking carcinoma on X-ray. The key distinguishing feature is the gradual transition between affected and normal bowel segments, unlike the abrupt demarcation seen in carcinoma. The sigmoid colon is often low-lying and angulated. Imaging from multiple angles is crucial for differentiating lesion characteristics.
Barium examination of the small intestine often shows predominant involvement of the terminal ileum. Filling with barium may reveal irregular luminal narrowing, angulation due to adhesions, spiculated shadows, thickened walls, and widened interloop spacing. Nodular filling defects resembling inflammatory bowel disease may also be seen. During emptying, the normal feathery mucosal pattern of the small intestine disappears. In recent years, mesenteric angiography has helped identify small vessel lesions, contributing to early diagnosis and differential diagnosis of radiation enteritis.
Assessment of small intestine absorption function: Includes fecal fat measurement, vitamin B12 absorption tests, and D-xylose absorption tests.
The diagnosis of this disease is generally not difficult. A history of radiotherapy combined with clinical manifestations and relevant examinations can determine the nature and location of the lesion, thereby confirming the diagnosis.
bubble_chart Treatment Measures
(1) General Treatment: During the acute phase, bed rest is recommended. The diet should follow the principles of being non-irritating, easily digestible, nutrient-rich, and consisting of multiple small meals. Limit fiber intake. For severe
diarrhea, intravenous hyperalimentation therapy may be used. (2) Drug Treatment:
1. Astringents and Antispasmodics: Belladonna mixture, compound formula camphor tincture, or Pomegranate Rind decoction (30g of Pomegranate Rind boiled in 200–300ml of water to reduce to 50ml, taken orally once daily) may be used. Aspirin can effectively control early-stage
diarrhea in radiation enteritis, possibly due to its inhibition of prostaglandin synthesis. 2. Topical Analgesics and Stool Softeners: For patients with significant
rectal urgency and pain, a 2% benzocaine cottonseed oil retention enema may be administered. Warm liquid paraffin retention enemas or warm sitz baths can also be used. 3. Hormonal Enemas: A retention enema with 50mg of amber hydrocortisone in 200ml of warm saline is effective, especially for those with
tenesmus. 4. Presacral Block Therapy: A mixture of 40ml of 0.5% procaine, 100mg of vitamin B6, 200mg of vitamin B1, 2–5mg of α-chymotrypsin, and 0.5g of streptomycin is administered every 5–7 days. After 1–3 treatments, pain is significantly reduced.
5. Hemostasis: For lower intestinal bleeding, hemostasis can be achieved under endoscopic visualization by compression, hemostatic agents, or figure-of-eight sutures at the bleeding site. Cauterization should not be used. For higher bleeding sites, a retention enema with 4–6mg of norepinephrine or 10–20mg of neosynephrine diluted in 200ml of warm saline may be used. Alternatively, 100–1000 units of thrombin in 200ml of warm saline can be administered as a retention enema, usually stopping bleeding within 1–3 minutes. Severe, uncontrolled high-level bleeding requires surgical intervention.
6. Anti-infection: Antibiotics are necessary for secondary infections.
7. α2 Macroglobulin: In China, α2 macroglobulin has been trialed for radiation enteritis with good results. Administer 6ml intramuscularly every other day or 3ml daily for 2 months as one course. After treatment, membrane bleeding and pain significantly improve, and ulcers tend to heal. The mechanism may involve inhibiting plasma kallikrein release, reducing capillary exudation and pain. Additionally, α2 macroglobulin binds to various proteolytic enzymes, inhibiting their effects on the intestinal wall.
(3) Surgical Treatment: Late-stage [third-stage] conditions such as intestinal strictures, obstructions, or fistulas often require surgical intervention. For distal colon lesions, a transverse colostomy may be performed for permanent or temporary fecal diversion, often yielding better outcomes than simple excision of distal lesions. Generally, the colostomy should remain for 6–12 months until colonic function recovers before closure.
(4)
Chinese Medicine Treatment: Chinese medicine views early gastrointestinal reactions to radiation as resulting from body fluid depletion and gastrointestinal heat accumulation. Symptoms include nausea, vomiting, and reduced appetite. Treatment focuses on tonifying yin and harmonizing the stomach. Herbs such as Inula Flower and Hematite are used to counterflow and stop vomiting; Coastal Glehnia Root, Polyghace Seche, and Reed Rhizome nourish yin and clear heat; tangerine peel, Bamboo Shavings, and Coix Seed resolve phlegm and harmonize the stomach. Acupuncture at Neiguan (PC6) and Zusanli (ST36) may also be applied. For proctitis, Chinese medicine attributes it to intestinal heat accumulation, presenting as abdominal pain, tenesmus, and bloody, purulent stools. Treatment involves enriching yin and clearing heat. Herbs like Japanese Pagodatree Pod, Sanguisorba, Patrinia, Chinese Pulsatilla Root, and Purslane Herb detoxify and clear heat; Peony Root, Smoked Plum, and Hawthorn Fruit promote sour-sweet transformation into yin; Ash Bark astringes and stops diarrhea. Acupuncture may also be combined.
For patients with radiation-induced leukopenia, Chinese medicine considers it as yin deficiency and blood deficiency. Symptoms include fatigue and weakness, pale complexion. Treatment should focus on tonifying qi and nourishing blood. Medicinals used include Astragalus Root and Solomonseal Rhizome to tonify qi; Chinese Angelica and suberect spatholobus stem to nourish blood and activate blood circulation; Dodder Seed, Barbary Wolfberry Fruit, and human placenta to tonify the kidneys and generate marrow. Additionally, 50% Ganoderma injection can be administered intramuscularly, 4ml each time, once daily, with 10 days constituting one treatment course.
Concurrent thrombocytopenia is considered in Chinese medicine as a deficiency of both qi and yin, with reckless movement of blood due to heat. Symptoms include fatigue, weakness, and hemorrhagic phenomena on the skin and mucous membranes. Treatment should focus on tonifying qi and nourishing yin, while cooling the blood to stop bleeding. Medicinals used include Astragalus Root, turtle carapace glue, tortoise-plastron glue, and Chinese Date to tonify qi and nourish yin; lalang grass rhizome, moutan bark, hairyvein agrimonia herb, and Small Thistle to clear heat and stop bleeding. For Chinese medicinals retention enema, use common bletilla pseudobulb 60g, Sanguisorba charcoal 20g, Sanqi powder 3g, add water to 1000ml, decoct until reduced to 500ml. Administer 50ml per session for retention enema, with 10 sessions constituting one course of treatment. The author has also used Indigo 3g, nitrofurazone powder 0.5g, 10% calcium gluconate injection 20ml, diluted with water to 500ml, administered once daily at 50ml per session for retention enema, with a 10-day course achieving satisfactory hemostatic effects.
The prognosis of radiation small intestine inflammation is worse than that of radiation colitis and proctitis. Two-thirds of mild cases can improve or recover within 4 to 18 months. Some believe that extensive pelvic surgery followed by radiotherapy further impairs blood supply to the affected tissues, often resulting in a poorer prognosis. According to foreign reports, the mortality rate of severe intestinal radiation injury is 22%.
During radium therapy for cervical carcinoma, the radium applicator should be securely fixed to prevent displacement and avoid tilting toward the posterior vaginal wall. For external beam radiation, the distance between the two pelvic irradiation fields should be no less than 4–6 cm. It is preferable to reduce the number of radium treatments from 3–4 sessions to 2. Some institutions use afterloading machines with specially designed straight retractors to separate the anterior rectal wall from the vaginal applicator by 1.5 cm, thereby reducing rectal radiation exposure. Patients showing signs of radiation proctitis should temporarily discontinue radiotherapy and receive other treatments.
The advanced stage manifestations of radiation enteritis and the recurrence and metastasis of cancerous tumors require X-ray barium contrast examination, mesenteric angiography, endoscopy, and biopsy for differentiation. In differential diagnosis, other diseases such as nonspecific ulcerative colitis, Crohn's disease, intestinal tuberculosis, and intestinal lipodystrophy syndrome (Whipple) should be considered.
