eMedicine Specialties > Gastroenterology > Intestine
Intestinal Radiation Injury
Updated: Jun 20, 2006
Introduction
Background
In 1897, 2 years after the discovery of x-rays by Roentgen, radiation-induced intestinal injury was first reported.
Although toxicity was the limiting factor in the early years, advancements in technology made delivering high doses of radiation possible to selective localized tissue targets, resulting in increased efficacy and increased utilization of radiation in the armamentarium of cancer therapy.
Many cancer patients receive some form of radiation as part of their cancer therapy; therefore, radiation-induced injury is likely to be a frequent occurrence despite improvements in radiation technology. Significant efforts have been made to develop methods to decrease or prevent radiation damage and to treat this dreadful complication.
This article focuses specifically on the effects of radiation on the small intestine, the large intestine, and the rectum.
Pathophysiology
Understanding the basic principles of how radiation affects the intestinal tract at the cellular level is important.
The new accepted unit dose of radiation is the gray (Gy); 1 Gy is equivalent to 100 rads. Although radiation injury can occur at doses of less than 40 Gy, serious injury usually occurs at doses greater than 50 Gy. Minimal tolerance (TD 5/5) is the dose that causes 5% of patients to have radiation injury within 5 years. While maximal tolerance (TD 50/5) is the dose at which 25-50% of patients manifest injury in 5 years. This translates to 45-65 Gy for the small intestine, 45-60 Gy for the colon, and 55-80 Gy for the rectum. The window of safety is narrow or perhaps nonexistent because the doses that cause injury are very close to the doses needed for therapy.
Cells are most sensitive to radiation during the G2 and M stages of mitotic division; therefore, rest periods between radiation sessions are important for the recovery of tissues. The most rapidly dividing cells are the most radiosensitive.
Radiation-induced injury is best described in 2 ways. Acute injury is a function of fractionation of the dose, field size, type of radiation, and frequency of treatment. Acute injury is caused by injury to the mitotically active intestinal crypt cells. On the other hand, chronic radiation injury is caused by injury to the less mitotically active vascular endothelial and connective tissue cells. Chronic injury is a function of the total dose of radiation used. This accounts for the described biphasic radiation injury.
Radiation injury impairs the normal repopulation of surface epithelium with growing new cells from the epithelial crypt cells. Repopulation normally takes place in 5-6 days. This impairment leads to varying degrees of retraction of villous core cells and spreading out of the enlarged villous epithelial cells. The loss of absorptive surface leads to malabsorption manifesting as diarrhea. Depending on the degree of disruption to the mucosal barrier by injury to the surface cells, microulcerations may form. The microulcerations can coalesce to form gross lesions. Intercellular tight junctions are disrupted, permitting the passage of endotoxin-containing particles from the lumen into the plasma.
Impairment to the blood supply by injury to capillary endothelium also contributes to the disruption. Invasion of the mucosa by intestinal microbes and sepsis may occur. Usually, therapeutic doses do not produce these profound consequences, and radiation treatment should be suspended or reduced when symptoms become significant. Crypt mitosis returns to normal within 3 days. Complete histologic recovery takes as long as 6 months. Chronic effects usually manifest after 6-24 months and are caused mostly by obliterative arteritis and thromboses of vessels; the result is ischemia or necrosis.
The combination of acute and chronic radiation injury can result in varying degrees of inflammation, thickening, collagen deposition, and fibrosis of the bowel, as well as impairment of mucosal and motor functions.
Frequency
United States
Although the exact incidence remains controversial, radiation enteritis is increasing and has been estimated to occur in 2-5% of patients receiving abdominal or pelvic radiotherapy. This incidence is expected to continue increasing.
Some investigators report much higher numbers of radiation enteritis, which may be explained by the extent of radiation field, the technique, and the dosage of radiation used.
The prevalence has been underestimated largely due to lack of clinical recognition and varies from 0.5-37%, depending on the radiation technique.
Mortality/Morbidity
The cumulative 10-year incidence of moderate injuries is estimated at 8%, and that of severe injuries is estimated at 3%, including bleeding and obstruction, stenosis and fistulization, and malabsorption and peritonitis.
Race
No predilection exists for any racial group.
Sex
No sex predilection exists.
Age
No predilection exists for any age group. Because most malignancies occur in older individuals, one expects this entity to be less of a problem in children.
Clinical
History
Symptoms can appear early, within hours of the first treatment session; very shortly after therapy; or months to years after the treatment has ended.
- Early presentation: In most situations, patients experience acute symptoms 2-3 weeks into the treatment. Symptoms usually resolve in 2-6 months. Symptoms tend to be self limited and mild in severity, requiring predominantly symptomatic therapy. The correlation between the severity of mucosal damage and the severity of symptoms appears to be poor. Symptoms include the following:
- Anorexia
- Nausea - More frequent with upper abdominal radiation
- Vomiting - More frequent with upper abdominal radiation
- Abdominal cramps - Consequence usually of small intestinal involvement
- Diarrhea - More often observed as a consequence of pelvic irradiation
- Tenesmus and mucoid rectal discharge - As a result of rectal involvement
- Rectal bleeding - As a result of rectal involvement
- Late presentation - Symptoms generally are insidious and develop months to years after therapy has ended. Many patients with chronic radiation enteritis may not have a prior history of acute radiation injury.
- Colicky abdominal pain - Most common late symptom, due to partial small bowel obstruction
- Nausea and vomiting - Consequences of small bowel obstruction
- Chronic watery diarrhea and/or steatorrhea - Consequence of multiple factors, including malabsorption, bile acid-mediated diarrhea, bacterial overgrowth, impaired motility, and development of fistulas
- Feculent vaginal discharge or pneumaturia - Consequence of fistula development
- Tenesmus, mucoid rectal discharge, rectal bleeding, constipation, and decrease in stool caliber - Consequences of rectal involvement
- Massive intestinal bleeding - Occurs rarely
- Acute onset of abdominal pain and toxemia - Rare occurrences, consequences of a free perforation
Physical
Physical examination varies, and findings can be normal or abnormal depending on the presence or absence of an underlying complication.
- Weight loss and malnutrition - Consequences of malabsorption
- Generalized and conjunctival pallor - Consequence of anemia
- Abdominal tenderness
- Peritoneal signs - Results of a free perforation
- Palpable mass on abdominal examination - Possible consequence of an inflammatory response
- Hyperactive bowel sounds, tinkling, rushes, and audible borborygmi - Possible consequences of bowel obstruction
- Rectal tenderness and bleeding - Occasional consequences of rectal involvement
Causes
Although radiation obviously is responsible for radiation-induced intestinal injury, certain predisposing factors increase the risk of radiation injury, as follows:
- Previous surgery causes the development of adhesions that tend to fix the intestines, which may be unable to be involved in the radiation field.
- Patients with hypertension, diabetes mellitus, and generalized atherosclerosis are at an increased risk for vascular occlusive disease.
- Thin, elderly, and female individuals may have more small intestine lying in the pelvis and may be subject to more radiation exposure.
- Hypoxic cells are less sensitive to radiation injury. Administering hyperbaric oxygen (HBO) at the time of radiation to increase tumor cell destruction also can increase damage to the healthy cells.
- Certain chemotherapeutic agents (eg, Adriamycin, methotrexate, 5-fluorouracil, bleomycin) increase sensitivity to radiation.
- Based on limited uncontrolled retrospective data, patients with underlying inflammatory bowel disease may be at a higher risk for severe toxicity.
More on Intestinal Radiation Injury |
Overview: Intestinal Radiation Injury |
| Differential Diagnoses & Workup: Intestinal Radiation Injury |
| Treatment & Medication: Intestinal Radiation Injury |
| Follow-up: Intestinal Radiation Injury |
| Multimedia: Intestinal Radiation Injury |
| References |
| Next Page » |
References
Abbasakoor F, Vaizey CJ, Boulos PB. Improving the morbidity of anorectal injury from pelvic radiotherapy. Colorectal Dis. Jan 2006;8(1):2-10.
Ajlouni M. Radiation-induced proctitis. Curr Treat Options Gastroenterol. Feb 1999;2(1):20-26. [Medline].
Andreyev J. Gastrointestinal complications of pelvic radiotherapy: are they of any importance?. Gut. Aug 2005;54(8):1051-4.
Babb RR. Radiation proctitis: a review. Am J Gastroenterol. Jul 1996;91(7):1309-11. [Medline].
Baum CA, Biddle WL, Miner PB. Failure of 5-aminosalicylic acid enemas to improve chronic radiation proctitis. Dig Dis Sci. May 1989;34(5):758-60. [Medline].
Campos FG, Waitzberg DL, Mucerino DR, et al. Protective effects of glutamine enriched diets on acute actinic enteritis. Nutr Hosp. May-Jun 1996;11(3):167-77. [Medline].
Churnratanakul S, Wirzba B, Lam T, et al. Radiation and the small intestine. Future perspectives for preventive therapy. Dig Dis. 1990;8(1):45-60. [Medline].
Cross MJ, Frazee RC. Surgical treatment of radiation enteritis. Am Surg. Feb 1992;58(2):132-5. [Medline].
Deutsch AA, Stern HS. Technique of insertion of pelvic Vicryl mesh sling to avoid postradiation enteritis. Dis Colon Rectum. Jul 1989;32(7):628-30. [Medline].
Donaldson SS, Jundt S, Ricour C, et al. Radiation enteritis in children. A retrospective review, clinicopathologic correlation, and dietary management. Cancer. Apr 1975;35(4):1167-78. [Medline].
Dubois A, Earnest DL. Radiation enteritis and colitis. In: Feldman M, Scharschmidt BF, Sleisenger MH, eds. Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 6th ed. Philadelphia, Pa:. WB Saunders Co;1998:1696-1707.
Empey LR, Papp JD, Jewell LD, Fedorak RN. Mucosal protective effects of vitamin E and misoprostol during acute radiation-induced enteritis in rats. Dig Dis Sci. Feb 1992;37(2):205-14. [Medline].
Feldman MI, Kavanah MT, Devereux DF, Choe S. New surgical method to prevent pelvic radiation enteropathy. Am J Clin Oncol. Feb 1988;11(1):25-33. [Medline].
Franzen L, Nyman J, Hagberg H, et al. A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy. Ann Oncol. Aug 1996;7(6):587-92. [Medline].
Fu YT, Lam JC, Tze JM. Measurement of irradiated small bowel volume in pelvic irradiation and the effect of a bellyboard. Clin Oncol (R Coll Radiol). 1995;7(3):188-92. [Medline].
Galland RB, Spencer J. Natural history and surgical management of radiation enteritis. Br J Surg. Aug 1987;74(8):742-7. [Medline].
Gavazzi C, Bhoori S, Lovullo S. Role of home parenteral nutrition in chronic radiation enteritis. Am J Gastroenterol. Feb 2006;101(2):374-9.
Gilinsky NH, Burns DG, Barbezat GO, et al. The natural history of radiation-induced proctosigmoiditis: an analysis of 88 patients. Q J Med. Winter 1983;52(205):40-53. [Medline].
Green N, Iba G, Smith WR. Measures to minimize small intestine injury in the irradiated pelvis. Cancer. Jun 1975;35(6):1633-40. [Medline].
Henriksson R, Bergstrom P, Franzen L, et al. Aspects on reducing gastrointestinal adverse effects associated with radiotherapy. Acta Oncol. 1999;38(2):159-64. [Medline].
Henriksson R, Franzen L, Littbrand B. Effects of sucralfate on acute and late bowel discomfort following radiotherapy of pelvic cancer. J Clin Oncol. Jun 1992;10(6):969-75. [Medline].
Horwhat JD, Dubois A. Radiation enteritis. Curr Treat Options Gastroenterol. 1999;2:371-381.
Jao SW, Beart RW Jr, Gunderson LL. Surgical treatment of radiation injuries of the colon and rectum. Am J Surg. Feb 1986;151(2):272-7. [Medline].
Kneebone A, Mameghan H, Bolin T. Effect of oral sucralfate on late rectal injury associated with radiotherapy for prostate cancer: A double-blind, randomized trial. Int J Radiat Oncol Biol Phys. Nov 15 2004;60(4):1088-97.
Lee DW, Poon AO, Chan AC. Diagnosis of small bowel radiation enteritis by capsule endoscopy. Hong Kong Med J. Dec 2004;10(6):419-21.
Localio SA, Stone A, Friedman M. Surgical aspects of radiation enteritis. Surg Gynecol Obstet. Dec 1969;129(6):1163-72. [Medline].
Lucarotti ME, Mountford RA, Bartolo DC. Surgical management of intestinal radiation injury. Dis Colon Rectum. Oct 1991;34(10):865-9. [Medline].
Mitsuhashi N, Takahashi I, Takahashi M, et al. Clinical study of radioprotective effects of amifostine (YM-08310, WR- 2721) on long-term outcome for patients with cervical cancer. Int J Radiat Oncol Biol Phys. Jun 15 1993;26(3):407-11. [Medline].
Nakada T, Kubota Y, Sasagawa I, et al. Therapeutic experience of hyperbaric oxygenation in radiation colitis. Report of a case. Dis Colon Rectum. Oct 1993;36(10):962-5. [Medline].
Nussbaum ML, Campana TJ, Weese JL. Radiation-induced intestinal injury. Clin Plast Surg. Jul 1993;20(3):573-80. [Medline].
Olgaç V, Erbil Y, Barbaros U. The efficacy of octreotide in pancreatic and intestinal changes: radiation-induced enteritis in animals. Dig Dis Sci. Jan 2006;51(1):227-32.
Russ JE, Smoron GL, Gagnon JD. Omental transposition flap in colorectal carcinoma: adjunctive use in prevention and treatment of radiation complications. Int J Radiat Oncol Biol Phys. Jan 1984;10(1):55-62. [Medline].
Saclarides TJ. Radiation injuries of the gastrointestinal tract. Surg Clin North Am. Feb 1997;77(1):261-8. [Medline].
Saclarides TJ, King DG, Franklin JL, Doolas A. Formalin instillation for refractory radiation-induced hemorrhagic proctitis. Report of 16 patients. Dis Colon Rectum. Feb 1996;39(2):196-9. [Medline].
Smit WG, Helle PA, van Putten WL, et al. Late radiation damage in prostate cancer patients treated by high dose external radiotherapy in relation to rectal dose. Int J Radiat Oncol Biol Phys. Jan 1990;18(1):23-9. [Medline].
Spitzer TR, Bryson JC, Cirenza E, et al. Randomized double-blind, placebo-controlled evaluation of oral ondansetron in the prevention of nausea and vomiting associated with fractionated total-body irradiation. J Clin Oncol. Nov 1994;12(11):2432-8. [Medline].
Swan RW, Fowler WC Jr, Boronow RC. Surgical management of radiation injury to the small intestine. Surg Gynecol Obstet. Mar 1976;142(3):325-7. [Medline].
Taylor JG, DiSario JA, Buchi KN. Argon laser therapy for hemorrhagic radiation proctitis: long-term results. Gastrointest Endosc. Sep-Oct 1993;39(5):641-4. [Medline].
Ugheoke EA, Norris T. Radiation Proctitis (RTP): Is there a role for hyperbaric oxygen (HBO) therapy?. Am J Gastroenterol. 1998;93:1700.
Willett CG, Ooi CJ, Zietman AL, et al. Acute and late toxicity of patients with inflammatory bowel disease undergoing irradiation for abdominal and pelvic neoplasms. Int J Radiat Oncol Biol Phys. Mar 1 2000;46(4):995-8. [Medline].
Woo TC, Joseph D, Oxer H. Hyperbaric oxygen treatment for radiation proctitis. Int J Radiat Oncol Biol Phys. Jun 1 1997;38(3):619-22. [Medline].
Yeoh E, Horowitz M. Radiation enteritis. Br J Hosp Med. Jun 1988;39(6):498-504. [Medline].
Further Reading
Keywords
radiation enteropathy, radiation enteritis, radiation colitis, radiation proctitis, radiation-induced intestinal toxicity, radiation-induced injury
Overview: Intestinal Radiation Injury