Radiation Enteritis

Epidemiology

• Acute radiation enteritis occurs in approximately 75% of patients undergoing abdominal/pelvic radiation.
• Chronic radiation enteritis develops in 5-15% of irradiated patients.
• The risk rises sharply with doses exceeding 5000 cGy (50 Gy); serious late complications are unusual below 4000 cGy.
• At doses of 70 Gy or greater, toxicity rises precipitously.

Pathophysiology

Acute Phase

• The small intestinal epithelium (with a turnover every 3-5 days) is acutely vulnerable.
• Radiation targets clonogenic stem cells in the crypts of Lieberkühn.
• Within 2-4 weeks: leukocyte infiltration, crypt microabscess formation, villus blunting, mucosal denudement, ulceration, and edema.
• Impaired absorption of fats, proteins, carbohydrates, bile salts, and vitamin B12.
• Impaired ileal bile salt absorption → conjugated bile salts reach the colon → deconjugation by bacteria → intraluminal salt/water accumulation → cholerheic diarrhea.
• Lactose maldigestion → bacterial fermentation → flatulence, distension, diarrhea.

Chronic Phase

• Progressive occlusive vasculitis / obliterative endarteritis of submucosal blood vessels (foam cell formation, subintimal fibrosis).
• Leads to chronic ischemia, submucosal fibrosis, and fibrotic changes affecting all layers of the bowel wall.
• Results in strictures, abscesses, fistulas, and ultimately vascular insufficiency with potential necrosis/perforation.
• Endothelial cell apoptosis actually precedes epithelial cell apoptosis, confirming vascular injury as the primary event.

Risk Factors

Clinical Presentation

Acute Radiation Enteritis

• Onset: During the 3rd week of a fractionated radiation course (typically after ~18-22 Gy)
• Symptoms: Nausea, vomiting, diarrhea (reported in 20-70% of patients), crampy abdominal pain, anorexia, malaise
• Course: Resolves within 2-6 weeks after completion of radiotherapy
• Diagnosis is clinical; CT is indicated if peritonitis signs develop to rule out other acute abdominal pathology.

Chronic Radiation Enteritis

• Onset: Usually within 18 months to 6 years after radiation (can appear from several months to up to 30 years later)
• Most affected segment: Terminal ileum
• Common presentations:
  • Diarrhea (from bile acid malabsorption, SIBO, dysmotility)
  • Partial/complete small bowel obstruction (nausea, vomiting, distension, crampy pain, weight loss)
  • Acute or chronic intestinal hemorrhage
  • Abscess or fistula formation
  • Malabsorption and nutritional deficiencies (B12, fat-soluble vitamins, steatorrhea)
  • Lactose intolerance
  • Protein-losing enteropathy

Diagnosis

• Review radiation treatment records: total dose, fractionation, treatment volume, high-dose areas.
• Enteroclysis (small bowel enema): Most accurate imaging for chronic radiation enteritis - sensitivity and specificity >90%. Shows widely separated loops, luminal narrowing, loss of mucosal folds, ulceration.
• CT scan: Less sensitive/specific than enteroclysis for mucosal detail, but best for assessing mural thickening.
  • Acute/subacute phase: "Target sign" - submucosal edema + mucosal hyperenhancement
  • Chronic fibrotic phase: Homogeneous mural thickening
• Radiological features (barium/CT): Thickening of valvulae conniventes, mural thickening, effacement of mucosal pattern, ulceration, fixation and angulation of loops. "Mucosal tacking" (spiking and distortion of antimesenteric mucosal folds from adhesions to inflamed mesentery) is characteristic. Luminal narrowing and sinuses/fistulae can be seen.
• Radiation-induced small bowel strictures are typically long and not amenable to endoscopic therapy.

Treatment

Acute Radiation Enteritis

• Antiemetics
• Oral hydration; IV fluids if severe diarrhea-induced dehydration
• Rarely requires dose reduction or cessation of radiation therapy

Chronic Radiation Enteritis

Surgical Management

• High-grade obstruction
• Perforation
• Hemorrhage
• Intra-abdominal abscess
• Fistula formation

• Goal: limited resection of diseased intestine with primary anastomosis between healthy (non-irradiated) bowel segments
• Distinguishing irradiated from normal bowel intraoperatively by gross inspection or frozen section is unreliable.
• Anastomosis between irradiated segments carries leak rates up to 50%.
• If limited resection is not achievable: intestinal bypass (except when hemorrhage is the indication, as bypass leaves the bleeding segment in situ).
• Extensive resections may lead to short bowel syndrome.
• Reported surgical mortality: ~10% (mean across series).

Prevention

• Keep total dose below 5000 cGy where clinically possible.
• Multibeam/multi-field radiation techniques to minimize peak exposure.
• Intensity-modulated radiotherapy (IMRT) and conformal radiotherapy.
• Tilt table positioning and bladder distention in prone position (moves bowel out of pelvis).
• Radiopaque clips (titanium) placed at original surgery for precise tumor targeting.

• Reperitonealization
• Omental transposition
• Absorbable mesh slings to keep small bowel out of the pelvis/radiation field

• ACE inhibitors and statins - reduce acute GI symptoms during pelvic RT
• Sucralfate - may help bleeding from radiation proctitis (no evidence for small bowel prevention)
• Superoxide dismutase (free radical scavenger)
• Pentoxifylline + tocopherols (vitamin E compounds)
• Amifostine (WR-2721) - sulfhydryl compound that scavenges free radicals
• Antioxidants (vitamins A, E, beta-carotene)
• Oral sulfasalazine - may reduce acute radiation-induced enteritis
• Probiotics (under active investigation in randomized trials)

• Acute enteritis (~75% incidence) is transient and self-limited; severity does NOT predict chronic disease.
• Chronic enteritis (5-15%) is driven by obliterative vasculitis and fibrosis - the vascular injury is the primary event.
• Terminal ileum is the most commonly affected site.
• Enteroclysis is the most accurate imaging test for chronic disease.
• Medical management is often unsatisfactory; surgery carries ~10% mortality.
• Anastomosis must be between healthy, non-irradiated bowel; irradiated-to-irradiated anastomoses leak in up to 50% of cases.