Radiation Enteritis

Content below is from a textbook reference chapter (Sabiston Ch50 - Diverticular Disease & Miscellaneous Problems), not primary literature.

Pathophysiology

Radiation therapy is generally used as adjuvant therapy for various abdominal and pelvic cancers. In addition to tumor cells, other rapidly dividing cells in normal tissues may be affected by radiation. Surrounding normal tissue, such as the small intestinal epithelium, may sustain severe, acute, and chronic deleterious effects. Radiation injury to the small bowel is subdivided into acute and chronic forms.

• Acute radiation-induced small bowel disease: manifests with colicky abdominal pain, bloating, loss of appetite, nausea, diarrhea, and fecal urgency during or shortly after a course of radiotherapy. Most patients notice symptoms during the third week of treatment, resolving 2–6 weeks after completion.
• Chronic radiation injury: typically develops between 18 months and 6 years after a completed course of radiotherapy, though symptoms can manifest up to 30 years after treatment. The amount of radiation correlates with the probability of developing enteritis — serious late complications are unusual if total dosage is <4000 cGy; morbidity risk increases with dosages exceeding 5000 cGy. Other risk factors: previous abdominal surgeries, preexisting vascular disease, hypertension, diabetes, and adjuvant treatment with certain chemotherapeutic agents (5-FU, doxorubicin, dactinomycin, MTX). A previous history of laparotomy increases enteritis risk, presumably because adhesions fix portions of the small bowel into the irradiated field. Radiation damage leads to symptoms of diarrhea, pain, and malabsorption. The late effects of radiation injury result from progressive damage to small submucosal blood vessels, with a progressive obliterative arteritis and submucosal fibrosis; these eventually result in thrombosis and vascular insufficiency. This injury produces necrosis and perforation of the involved intestine but, more commonly, leads to stricture formation with symptoms of obstruction or small bowel fistulas.

Prevention

Multiple strategies are used to reduce radiation injury to the small bowel (Box 50.8 in the source): adjusting radiation ports/dosages to deliver optimal treatment specifically to the tumor and not to surrounding tissues; placement of radiopaque markers (titanium clips) at the original operation to facilitate better targeting of radiation treatment; reduction in field size, multiple field arrangements, conformal radiotherapy techniques, and intensity-modulated radiotherapy to reduce toxicity; methods to exclude the small bowel from the irradiated field, including reperitonealization, omental transposition, and placement of absorbable mesh slings.

A number of pharmacologic interventions have also been described to reduce radiation enteritis side effects: angiotensin-converting enzyme inhibitors and statins significantly reduce acute GI symptoms during radical pelvic radiotherapy. Sucralfate (a highly sulfated polyanionic disaccharide) has been thought to stimulate epithelial healing and form a protective barrier over damaged mucosal surfaces, and may help treat bleeding from radiation proctitis, but no evidence supports its use in preventing radiation-induced small bowel disease. Superoxide dismutase (a free radical scavenger) has been used successfully to reduce complications. Other evaluated compounds include glutathione, antioxidants (vitamin A, vitamin E, beta-carotene), histamine antagonists, and pentoxifylline + tocopherols (a chemical compound combination with vitamin E activity). Early studies support probiotic use as radioprotective in the gut, though further studies are needed before a final assessment can be made. The most effective radioprotectant agent appears to be amifostine (WR-2721), a sulfhydryl compound that is converted intracellularly to an active metabolite, WR-1065, which binds free radicals and protects the cell from radiation injury. A randomized controlled trial determined that glutamine offers little benefit even when used before or during radiation therapy. Agents that may prove useful in preventing acute radiation enteritis symptoms include the hormones bombesin, growth hormone, GLP-2, and IGF-I, which in experimental studies demonstrated effectiveness in preventing or reducing symptoms associated with radiation enteritis.

Treatment

Acute radiation enteritis is directed at controlling symptoms. Antispasmodics and analgesics may alleviate abdominal pain/cramping; diarrhea usually responds to opiates or other antidiarrheal agents. Corticosteroids are of uncertain value. Dietary manipulation, including oral elemental diets, has been advocated to ameliorate acute effects, though results are conflicting. Antibiotics are frequently used in the setting of bacterial overgrowth. Bile acid malabsorption, thought responsible for diarrheal symptoms in 35–72% of patients with radiation-induced small bowel disease, responds well to cholestyramine, though it is not well tolerated and many patients voluntarily discontinue use.

Operative intervention may be required for a subgroup of patients with chronic radiation enteritis effects — a small (1–2%) subgroup of the total number who received abdominal/pelvic irradiation. Indications for operation include obstruction, fistula formation, perforation, and bleeding, with obstruction being the most common presentation. Operative procedures include bypass or resection with reanastomosis. Advocates for bypass procedures contend this procedure is safer and controls symptoms better than resection; advocates for resection contend the high morbidity/mortality rates previously reported with resection and reanastomosis reflect inadequate resection and anastomosis of diseased intestine. In patients presenting with obstruction, extensive lysis of adhesions should be avoided. Obstruction caused by rigid, fixed intestinal loops in the pelvis is best bypassed. If resection and reanastomosis are planned, at least one end of the anastomosis should be from intestine outside the irradiated field. Macroscopic inspection may not be accurate in evaluating the full extent of radiation damage — frozen section and laser Doppler flowmetry techniques have been used to assist resection/anastomosis decisions. Perforation of the intestine should be treated with resection and anastomosis; when reanastomosis is thought to be unsafe, the ends should be exteriorized.

Open items / gaps

• No primary literature yet in the wiki independently appraising the glutamine RCT or the specific pharmacologic prevention agents listed — currently only the textbook’s narrative summary.