eMedicine Specialties > Gastroenterology > Intestine

Intestinal Radiation Injury

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

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