Radiation Enteritis

Etiology

Radiation enteritis is an unavoidable side effect of radiotherapy, although its development is highly variable, depending on the duration, dosage, and gut sensitivity to radiation.[2]

Epidemiology

Radiation enteritis is very common; studies have reported a permanent change in bowel habits in 90% of patients that undergo pelvic radiotherapy.[1] Some evidence shows that it may be more common in patients getting radiation therapy for gastrointestinal (GI) and gynecological tumors than urological tumors.[3] Chronic radiation enteritis occurs in approximately 5% to 55% of patients post-radiotherapy.[4]

Pathophysiology

The repetitive injuries[1] caused to the intestinal mucosa by ionizing radiation, as well as its complex mechanism of healing, are proposed to cause radiation enteritis. Exposure of normal tissues to radiation leads to the production of reactive ions that combine with intracellular water molecules to form radicals like hydroxyl and other free radicals. These radicals are deemed responsible for causing breaks in DNA and causing cell death. Secondary to radiation exposure, activation of genes that are responsible for the translation of transforming growth factor (TGF-beta) takes place. This activation stimulates collagen and fibronectin genes promoting fibrosis. Tissues with rapid proliferation are sensitive to radiation, and thus, cell membrane disruption is also responsible for the cell death observed. The epithelial cells of the small intestine are more radiosensitive as compared to the colon and rectum. Studies show that the presence of Bcl2 in the rectum is the reason for this discrimination. The most characteristic pathologic changes observed are fibrosis and obliterative endarteritis in the intestinal epithelium.[5]

Histopathology

The initial changes can be observed 2 to 3 hours following radiation and are mainly inhibition of epithelial apoptosis in the crypts. They appear smaller with time as the migration of epithelial cells continues despite continued cell death. With time, the villi cells are lost; this leads to the absence of infectious and fluid barriers of the intestine. Apoptotic fragments consisting of nuclear or cytoplasm fragments and condensation of cytoplasm may also be visible.[5][6][7]

History and Physical

Diarrhea associated with or without pain is the most common symptom.[5] Other symptoms are:

• Abdominal pain
• Intestinal hemorrhage
• Intestinal obstruction
• Intestinal perforation
• Fistulas
• Malabsorption
• Rectal pain
• Rectal bleeding secondary to ulceration

Evaluation

Patients with diarrhea, abdominal pain, or bloating should also undergo breath testing for bacterial overgrowth.

CT and MRI are used to see pathological changes not observed on conventional imaging. Pill enterography is not advisable, as there are risks associated with it getting trapped; whereas, endoscopic evaluation is considered when there is a possibility of colonic anastomosis. Demarcation of involved intestinal segments should be done to correlate radiologic findings and clinical presentation.

Many scoring systems exist to assess the severity of symptoms in patients undergoing radiotherapy but none succeeded in fulfilling the purpose.

Postradiotherapy, attempts should be made to aggressively look for recurrence of the tumor with the help of PET-CT and tumor markers.

Treatment / Management

• Symptoms of acute radiation enteritis often self-resolve within weeks of supportive treatment with antimotility agents and good water intake; surgery is rarely needed.
• Antioxidant administration during radiotherapy has been shown to increase efficacy and decrease the side effect profile. [5]
• Oral antibiotics are given to patients suspected of having bacterial overgrowth, along with vitamins and electrolytes replacement if needed.
• If malnourishment is suspected, patients should be checked for decrease intake and/or malabsorption. Surgical removal in patients with mechanical malabsorption does not relieve symptoms.
• Mild bleeding and minimal symptoms do not require further treatment.
• First-line treatment for radiation proctitis and tenesmus includes enemas, for example, the sucralfate enema.
• As a consequence of chronic radiation, Patients who have enteritis leading to the formation of intestinal strictures, fistulas, and perforations require surgical procedures. One study showed high postoperative morbidity (74.8%) after the first surgical procedure. Many patients required parenteral nutrition after surgery. Data indicates repeated surgical procedures may be needed; they do not seem to increase the morbidity.
• It is important to resect the whole irradiated bowel in the first operation to reduce the need for more surgical procedures, but it is not a suitable option in every case due to fear of complications such as short bowel syndrome.[4]

Differential Diagnosis

Differential diagnoses considered in patients presenting with symptoms similar to radiation enteritis include:

• Bowel infection
• New/recurrent malignancy
• Small intestinal bacterial overgrowth
• Pancreatic insufficiency
• Inflammatory bowel disease (new-onset)

Surgical Oncology

Simple procedures like adhesiolysis and bypass are less beneficial as compared to removal of the entire diseased bowel.[4]

Radiation Oncology

Baxter and Collegues (2005) reviewed more than 85,000 men treated for prostate cancer between 1973 and 1994 and found a direct relationship between radiotherapy and the development of rectal cancer when compared to patients treated with surgery alone. The hazard ratio was found to be 1.7 (95% CI: 1.4 to 2.2). Various modalities have been developed to enhance the efficacy profile of radiotherapy to the target organ and reduce its side effect profile. Some of these include 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy (IMRT), and stereotactic body radiotherapy (SBRT), but the possibility of microscopic disease broadens the treatment field and ultimately leads to exposure of normal tissues.

German Rectal Cancer trial showed that preoperative chemoradiation leads to lower toxicity rates as compared to the postoperative method.[8]

Prognosis

The development of radiation enteritis has been shown to be dependent on factors such as:

• Radiation dose
• Past abdominal surgery
• Body mass index
• Comorbid conditions like diabetes mellitus, hypertension
• Concurrent chemotherapy[9]

Statistics show a large number of patients undergoing surgery for radiotherapy-induced gut damage die from their original cancer within the period of 2 years. Whereas without cancer recurrence, the 5-year survival is approximately 70%.

Complications

Ongoing studies have shown an increased risk of malignancy as a late consequence of pelvic radiation.