Intestinal Radiation Injury 

  • Author: Rajeev Vasudeva, MD, FACG; Chief Editor: Julian Katz, MD   more...
 
Updated: Mar 22, 2011
 

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. In addition, events such as the explosions at Japan's Fukushima Daiichi nuclear power plant in March of 2011 ignite concerns of radiation exposure, which can lead to radiation-induced injury.

Significant efforts have been made to develop methods to decrease or prevent radiation damage and to treat this dreadful complication.

Recent studies

Michalski et al, in a Phase I/II dose-escalation trial of a 3-dimensional conformal radiation therapy (3DCRT; RTOG 9406) for prostate cancer, reported on the incidence of late toxicity. The patients were divided into 3 groups: group I patients were treated at the prostate only; group 2 patients were treated at the prostate and at the seminal vesicles with a prostate boost; and group 3 patients were treated at the prostate and seminal vesicles. The authors stated that their findings showed that tolerance to high-dose 3DCRT was excellent but that there was significantly more grade 2 or greater toxicity with a dose of 78 Gy at 2 Gy/fraction than with 68.4-79.2 Gy at 1.8 Gy/fraction and with 74 Gy at 2 Gy/fraction.[1]

McCammon et al evaluated 30 patients with intermediate- to high-risk prostate cancer to determine the toxicity associated with pelvic intensity-modulated radiotherapy (IMRT) and hypofractionated simultaneous integrated boost (SIB). In addition, the patients received androgen suppression. Using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, to score toxicity, the investigators found that, at a median follow-up of 24 months, late toxicity was uncommon that exceeded grade-2 severity; there were 2 occurrences of grade-3 toxicity and 1 case of grade 4.[2]

Images of radiation-induced intestinal injuries are shown below.

Intestinal radiation injury. Characteristic mucosaIntestinal radiation injury. Characteristic mucosal changes observed in radiation proctitis with multiple telangiectasias. Intestinal radiation injury. Friability and oozingIntestinal radiation injury. Friability and oozing of blood from atrophic-appearing mucosa due to radiation. This slide illustrates disorderly crypts, fibrosisThis slide illustrates disorderly crypts, fibrosis of lamina propria, and vascular dilatation, all of which are characteristic of colonic injury due to radiation. (This slide was provided courtesy of Ronald Burns, MD, Palmetto Richland Memorial Hospital, Columbia, SC.)

This article focuses specifically on the effects of radiation on the small intestine, the large intestine, and the rectum.

Next

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.[3]

Previous
Next

Epidemiology

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.[4, 5] 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% to 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.

Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

Rajeev Vasudeva, MD, FACG  Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine

Rajeev Vasudeva, MD, FACG is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, Columbia Medical Society, South Carolina Gastroenterology Association, and South Carolina Medical Association

Disclosure: Pricara Honoraria Speaking and teaching; UCB Consulting fee Consulting

Specialty Editor Board

Anil Minocha, MD, FACP, FACG  Professor of Medicine, Director of Digestive Diseases, Medical Director of Nutrition Support, Medical Director of Gastrointestinal Endoscopy, Internal Medicine Department, University of Mississippi Medical Center; Clinical Professor, University of Mississippi School of Pharmacy

Anil Minocha, MD, FACP, FACG is a member of the following medical societies: American Academy of Clinical Toxicology, American Association for the Study of Liver Diseases, American College of Forensic Examiners, American College of Gastroenterology, American College of Physicians, American Federation for Clinical Research, American Gastroenterological Association, and American Society of Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Douglas M Heuman, MD, FACP, FACG, AGAF  Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

References

  1. Michalski JM, Bae K, Roach M, Markoe AM, Sandler HM, Ryu J, et al. Long-term toxicity following 3D conformal radiation therapy for prostate cancer from the RTOG 9406 phase I/II dose escalation study. Int J Radiat Oncol Biol Phys. Jan 1 2010;76(1):14-22. [Medline].

  2. McCammon R, Rusthoven KE, Kavanagh B, Newell S, Newman F, Raben D. Toxicity assessment of pelvic intensity-modulated radiotherapy with hypofractionated simultaneous integrated boost to prostate for intermediate- and high-risk prostate cancer. Int J Radiat Oncol Biol Phys. Oct 1 2009;75(2):413-20. [Medline].

  3. Gervaz P, Morel P, Vozenin-Brotons MC. Molecular aspects of intestinal radiation-induced fibrosis. Curr Mol Med. Apr 2009;9(3):273-80. [Medline].

  4. Green N, Iba G, Smith WR. Measures to minimize small intestine injury in the irradiated pelvis. Cancer. Jun 1975;35(6):1633-40. [Medline].

  5. 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].

  6. Kopelman Y, Groissman G, Fireman Z. Radiation enteritis diagnosed by capsule endoscopy. Gastrointest Endosc. Sep 2007;66(3):599; discussion 599. [Medline].

  7. 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. [Medline].

  8. Yang XY, Chen CX, Zhang BL, et al. Diagnostic effect of capsule endoscopy in 31 cases of subacute small bowel obstruction. World J Gastroenterol. May 21 2009;15(19):2401-5. [Medline].

  9. Alfadhli AA, Alazmi WM, Ponich T, et al. Efficacy of argon plasma coagulation compared to topical formalin application for chronic radiation proctopathy. Can J Gastroenterol. Feb 2008;22(2):129-32. [Medline].

  10. Qiu W, Leibowitz B, Zhang L, Yu J. Growth factors protect intestinal stem cells from radiation-induced apoptosis by suppressing PUMA through the PI3K/AKT/p53 axis. Oncogene. Dec 7 2009;epub ahead of print. [Medline].

  11. Valuckaite V, Zaborina O, Long J, et al. Oral PEG 15-20 protects the intestine against radiation: role of lipid rafts. Am J Physiol Gastrointest Liver Physiol. Dec 2009;297(6):G1041-52. [Medline].

  12. 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].

  13. Demirer S, Aydintug S, Aslim B, et al. Effects of probiotics on radiation-induced intestinal injury in rats. Nutrition. Feb 2006;22(2):179-86. [Medline].

  14. Seal M, Naito Y, Barreto R, Lorenzetti A, Safran P, Marotta F. Experimental radiotherapy-induced enteritis: a probiotic interventional study. J Dig Dis. Aug 2007;8(3):143-7. [Medline].

  15. Ciorba MA, Stenson WF. Probiotic therapy in radiation-induced intestinal injury and repair. Ann N Y Acad Sci. May 2009;1165:190-4. [Medline].

  16. Abbasakoor F, Vaizey CJ, Boulos PB. Improving the morbidity of anorectal injury from pelvic radiotherapy. Colorectal Dis. Jan 2006;8(1):2-10. [Medline].

  17. Abderrahmani R, François A, Buard V, et al. Effects of pharmacological inhibition and genetic deficiency of plasminogen activator inhibitor-1 in radiation-induced intestinal injury. Int J Radiat Oncol Biol Phys. Jul 1 2009;74(3):942-8. [Medline].

  18. Ajlouni M. Radiation-induced proctitis. Curr Treat Options Gastroenterol. Feb 1999;2(1):20-26. [Medline].

  19. Andreyev J. Gastrointestinal complications of pelvic radiotherapy: are they of any importance?. Gut. Aug 2005;54(8):1051-4. [Medline].

  20. Babb RR. Radiation proctitis: a review. Am J Gastroenterol. Jul 1996;91(7):1309-11. [Medline].

  21. 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].

  22. 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].

  23. 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].

  24. Cross MJ, Frazee RC. Surgical treatment of radiation enteritis. Am Surg. Feb 1992;58(2):132-5. [Medline].

  25. 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].

  26. 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].

  27. 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.

  28. 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].

  29. 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].

  30. 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].

  31. 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].

  32. Galland RB, Spencer J. Natural history and surgical management of radiation enteritis. Br J Surg. Aug 1987;74(8):742-7. [Medline].

  33. Gavazzi C, Bhoori S, Lovullo S, Cozzi G, Mariani L. Role of home parenteral nutrition in chronic radiation enteritis. Am J Gastroenterol. Feb 2006;101(2):374-9. [Medline].

  34. Hauer-Jensen M, Wang J, Boerma M, Fu Q, Denham JW. Radiation damage to the gastrointestinal tract: mechanisms, diagnosis, and management. Curr Opin Support Palliat Care. Apr 2007;1(1):23-9. [Medline].

  35. 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].

  36. 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].

  37. Horwhat JD, Dubois A. Radiation enteritis. Curr Treat Options Gastroenterol. 1999;2:371-381.

  38. 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].

  39. 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.

  40. Localio SA, Stone A, Friedman M. Surgical aspects of radiation enteritis. Surg Gynecol Obstet. Dec 1969;129(6):1163-72. [Medline].

  41. Lucarotti ME, Mountford RA, Bartolo DC. Surgical management of intestinal radiation injury. Dis Colon Rectum. Oct 1991;34(10):865-9. [Medline].

  42. 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].

  43. 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].

  44. Nussbaum ML, Campana TJ, Weese JL. Radiation-induced intestinal injury. Clin Plast Surg. Jul 1993;20(3):573-80. [Medline].

  45. Olgac V, Erbil Y, Barbaros U, et al. The efficacy of octreotide in pancreatic and intestinal changes: radiation-induced enteritis in animals. Dig Dis Sci. Jan 2006;51(1):227-32. [Medline].

  46. 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].

  47. Saclarides TJ. Radiation injuries of the gastrointestinal tract. Surg Clin North Am. Feb 1997;77(1):261-8. [Medline].

  48. 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].

  49. 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].

  50. 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].

  51. 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].

  52. 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].

  53. Ugheoke EA, Norris T, Sharma VK, et al. Radiation proctitis(RTP): Is there a role for hyperbaric oxygen (HBO) therapy? Paper presented at: Proceedings of the American College of Gastroenterology 63rdAnnual Scientific Meeting; October 12-14, 1998; Boston, Mass.

  54. 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].

  55. Yeoh E, Horowitz M. Radiation enteritis. Br J Hosp Med. Jun 1988;39(6):498-504. [Medline].

  56. Zimmerer T, Böcker U, Wenz F, Singer MV. Medical prevention and treatment of acute and chronic radiation induced enteritis--is there any proven therapy? a short review. Z Gastroenterol. May 2008;46(5):441-8. [Medline].

 
Previous
Next
 
Intestinal radiation injury. Characteristic mucosal changes observed in radiation proctitis with multiple telangiectasias.
Intestinal radiation injury. Friability and oozing of blood from atrophic-appearing mucosa due to radiation.
Intestinal radiation injury. Appearance of mucosa after therapy with bipolar circumactive probe (BICAP) probe.
This slide illustrates disorderly crypts, fibrosis of lamina propria, and vascular dilatation, all of which are characteristic of colonic injury due to radiation. (This slide was provided courtesy of Ronald Burns, MD, Palmetto Richland Memorial Hospital, Columbia, SC.)
A deep rectal ulcer from prostate cancer radiation years ago. Patient presented with significant rectal bleeding.
After 6 months of treatment with daily Canasa (5-ASA) suppositories
Retroflexed view of the same radiation induced ulcer after 6 months of treatment
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.