Radiation Enteritis and Proctocolitis




Background


Radiation was first used as a treatment modality for breast cancer in 1896, and a year later Dr. David Walsh, a physician at the Western Skin Hospital, London, described the first case of radiation enteritis. A “practical worker” had “gastric symptoms, such as pain, tenderness on pressure, flatulency, colic, and diarrhea” after 2 hours of daily exposure to radiation. The symptoms resolved after the worker started using an abdominal lead shield.


Today, radiation therapy is a common treatment for gynecologic, urologic, and rectal malignancies. Exclusion of “innocent” bowel from the radiation field during radiotherapy can be difficult, and when adjacent bowel gets in the way, radiation enteritis can result. The incidence of radiation enteritis and proctocolitis varies according to cancer type because treatment regimens vary between the different types of pelvic malignancies.




Pathophysiology


When the electromagnetic waves of radiation hit normal tissue, they cause the release of electrons, which form hydroxyl or free radicals. The hydroxyl radical induces apoptosis. Rapidly proliferating cells in the G2 and M phases of mitosis, such as cancer cells, or stem cells in intestinal crypts, are most affected by radiation. Regulator genes involved in this process include CRADDD , APAF1 , p53 , BCL2 , XRCC1 , XRCC3 , and BCL2 . Ionizing radiation also activates the translation of transforming growth factor–β.


Radiation enteritis is categorized as acute and chronic. Acute injury occurs during radiotherapy and may last up to 6 months, whereas chronic injury occurs after 3 months and may even present 50 years after radiation was administered. Radiation is “the gift that keeps on giving.”


In the acute process, radiation prevents epithelial cell mitosis deep within the mucosal crypts; however, it does not inhibit cell migration out of the crypts onto villi, which leads to denuding of the mucosal protective barrier. Bacteria and other antigens can violate the mucosa, causing an inflammatory response and bacteremia. Histologic findings include inflammatory infiltrates, reduced crypt mitoses, crypt microabscesses, and epithelial ulceration. Progressive collagen deposition, an obliterative vasculitis and submucosal fibrosis, lymphatic dilation, and tissue ischemia and necrosis also occur.


Secondary colorectal malignancies occur in up to 20% of patients after radiotherapy, and the time between irradiation to the emergence of a solid tumor averages 10 years. Eight percent have been linked to previous radiation therapy, and two thirds were found to be rectosigmoid malignancies.




Predisposing Risk Factors


The major risk factors for the development of radiation enteritis are the volume of bowel exposure to the radiation field and radiation dosage ( Table 80-1 ). Other risk factors include adhesions that prevent the bowel from being excluded from the field, radiation delivery techniques, and the use of radiosensitizing chemotherapeutic agents, such as fluorouracil and mitomycin.



TABLE 80-1

Predisposing Risk Factors for Radiation Toxicity to Bowel












Volume of bowel exposure to radiation Radiation field
Radiation dosage
Radiation delivery techniques
Patient positioning
Radiosensitizing chemotherapeutic agents
Fluorouracil
Mitomycin
Consequential late effect Patients who experienced extreme symptoms of acute radiation injury
Comorbid factors Adhesive disease after abdominal or pelvic surgery
Combined modality therapy
Collagen vascular disease
Inflammatory bowel disease
Human immunodeficiency virus
Thinner patients
History of vascular occlusive disease
Hypertension
Diabetes
Smoking
Atherosclerosis
Cardiovascular disease


Patients who experience extreme symptoms of acute radiation injury have a higher risk of the development of chronic radiation enteritis, which is called consequential late effect .


Comorbid factors that increase the risk of radiation bowel injury include collagen vascular diseases, inflammatory bowel disease, human immunodeficiency virus infection, and a history of vascular occlusive disease, such as hypertension, diabetes, smoking, atherosclerosis, and cardiovascular disease. It is hypothesized that thinner patients with a smaller anterior-posterior diameter have an increased risk of intestinal toxicity.




Grading Systems


Toxicity grading systems have been proposed but have limited clinical utility. The most common toxicity grading systems are those proposed by the Radiation Therapy Oncology Group (RTOG; Table 80-2 ) and the European Oncology Radiation Therapy Group (EORTG). The RTOG criteria assess short-term effects of radiation, whereas RTOG and EORTG criteria assess long-term effects. Other systems are the Late Effects on Normal Tissues Subjective, Objective, Management and Analytic grading system and the Common Terminology Criteria for Adverse Events.



TABLE 80-2

Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria: Lower Gastrointestinal, Including Pelvis





















Grade 0 No change
Grade 1 Increased frequency or change in quality of bowel habits not requiring medication
Rectal discomfort not requiring analgesics
Grade 2 Diarrhea requiring parasympatholytic drugs (e.g., diphenoxylate/atropine [Lomotil])
Mucous discharge not necessitating sanitary pads
Rectal or abdominal pain requiring analgesic drugs
Grade 3 Diarrhea requiring parenteral support
Severe mucous or blood discharge necessitating use of sanitary pads
Abdominal distention (a flat plate radiograph demonstrates distended bowel loops)
Grade 4 Acute or subacute obstruction, fistula, or perforation
Gastrointestinal bleeding requiring transfusion
Abdominal pain or tenesmus requiring tube decompression or bowel diversion
Grade 5 Death




Diagnostic Workup


Symptoms of radiation enteritis are nonspecific, and the differential diagnosis is broad (see Box 80-1 ). The timing of the symptoms suggests the diagnosis. Acute enteritis is generally an abrupt illness with nausea, vomiting, diarrhea, and bleeding. Chronic enteritis is more gradual onset of initially vague abdominal pain or discomfort, constipation, and nausea. Patients with acute enteritis usually have tenderness upon abdominal palpation as a result of the active inflammation, whereas persons with chronic enteritis usually do not have tenderness.



BOX 80-1





  • New or recurrent neoplasia



  • Intestinal stricture



  • Intestinal fistula



  • Small bowel bacterial overgrowth



  • Bile salt, fat, or carbohydrate malabsorption



  • New diagnosis of inflammatory bowel disease



  • Pancreatic insufficiency



  • Irritable bowel syndrome



Differential Diagnosis of Gastrointestinal Symptoms after Radiation Therapy


Laboratory testing, including tumor markers to rule out recurrence or a secondary malignancy, should be performed. Computed tomography (CT) scanning or magnetic resonance imaging (MRI) and upper or lower endoscopy are useful imaging procedures to make the diagnosis and establish the location and extent of the disease. Enteroscopy or capsule endoscopy also may be helpful, but in patients with chronic enteritis, strictures may exclude their use. Biopsies are usually nonspecific but can rule out other causes of inflammation. Biopsies of chronic radiation enteritis often show evidence of ischemia because of the stenosing vasculitis that is a feature of the disease.




Prevention


Careful planning can minimize exposure to radiation. Physical maneuvers have been attempted, such as prone positioning, use of a “belly board,” and distension of the bladder to displace the small bowel out of the pelvis. In addition, tissue expanders, biodegradable mesh slings, and intrapelvic breast prostheses have been shown to minimize pelvic radiation exposure by up to 50%. CT scanning simulation techniques, intensity-modulated radiation therapy, and brachytherapy targeting radiation to the cancer decrease extraneous exposure compared with nonspecific external beam radiation.

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Jul 15, 2019 | Posted by in GENERAL | Comments Off on Radiation Enteritis and Proctocolitis
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