Radiation enteritis is damage to small and/or large intestine secondary to radiation. Different terms like radiation colitis, radiation enteropathy, radiation mucositis, and pelvic radiation disease have been used to describe this phenomenon. Radiation proctitis is a different term that is used to describe the involvement of rectum and sigmoid colon. Radiotherapy is used as a treatment for many cancers. Radiation enteritis can be acute or chronic. The chronic form usually develops between 3 months to 30 years after treatment.
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.
Radiation enteritis is very common; studies have reported a permanent change in bowel habits in 90% of patients that undergo pelvic radiotherapy. Some evidence that shows that it may be more common in patients getting radiation therapy for gastrointestinal (GI) and gynecological tumors than urological tumors. Chronic radiation enteritis occurs in approximately 5% to 55% of patients post radiotherapy.
The repetitive injuries caused to the intestinal mucosa by ionizing radiation, as well as its complex mechanism of healing, is 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.
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 barrier of the intestine. Apoptotic fragments consisting of nuclear or cytoplasm fragments and condensation of cytoplasm may also be visible.
Diarrhea associated with or without pain is the most common symptom. Other symptoms are:
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.
Differential diagnoses considered in patients presenting with symptoms similar to radiation enteritis include:
Simple procedures like adhesiolysis and bypass are less beneficial as compared to removal of the entire diseased bowel.
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.
Development of radiation enteritis has been shown to be dependent on factors such as:
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%.
Ongoing studies have shown an increased risk of malignancy as a late consequence of pelvic radiation.
Surgical approach to treat radiation enteritis has a high risk of postoperative morbidity, and about 30% of cases often need succeeding surgical procedures. Some of the common morbidities are:
Patients should maintain adequate hydration and avoid foods that cause discomfort. Risk of malignancy and recurrence should be conveyed and watched for during follow-up visits.
Radiation enteritis is an unavoidable side effect of radiotherapy; however, its development is highly variable.
It is becoming more common with the advent of new treatment regimens for different cancers including radiotherapy.
Diarrhea, abdominal pain, intestinal hemorrhage, intestinal obstruction, intestinal perforation, fistulas, malabsorption, rectal pain, and rectal bleeding secondary to ulceration are some of the common symptoms.
It can be treated with supportive measures or surgically.
Prognosis varies in different patients, and they should be followed regularly to observe for recurrence of malignancy.
The care of patients with radiation enteritis is an interprofessional. Besides the surgeon, radiation oncologist, gastroenterologist and radiologist, the nurse and dietitian is a vital member of the team. While not all complications of radiation enteritis can be prevented, the patient's nutritional state should be improved prior to any surgery. The patient should be educated about the potential complications and the need for repeat surgery. The patient should be seen by a stoma nurse in case a colostomy or ileostomy is performed during surgery. More important the patient should be told about the short bowel syndrome and the need for long-term parenteral nutrition. After surgery, the routine surgical complications like deep vein thrombosis and atelectasis should be prevented with prophylactic treatment with LWMH and use of the incentive spirometer, respectively. Finally, the family and the patient should be educated on end-of-life preparation and designation of a power of attorney. (Level V)
When surgery is performed on the radiated intestine, this carries a high morbidity and mortality. Complications that can result include non-healing of wounds, a breakdown of the intestinal anastomosis, pelvic abscess, secondary malignancy, and fistula formation. An anastomotic leak can carry a mortality rate of 30-50% in the presence of radiation enteritis. Even those who survive may require additional surgical procedures to repair the fistula. And the repeat surgery also carries additional mortality. The quality of life for patients who suffer from complications of radiation enteritis is poor. (Level V)
|||Stacey R,Green JT, Radiation-induced small bowel disease: latest developments and clinical guidance. Therapeutic advances in chronic disease. 2014 Jan [PubMed PMID: 24381725]|
|||Kountouras J,Zavos C, Recent advances in the management of radiation colitis. World journal of gastroenterology. 2008 Dec 28 [PubMed PMID: 19109862]|
|||Olopade FA,Norman A,Blake P,Dearnaley DP,Harrington KJ,Khoo V,Tait D,Hackett C,Andreyev HJ, A modified Inflammatory Bowel Disease questionnaire and the Vaizey Incontinence questionnaire are simple ways to identify patients with significant gastrointestinal symptoms after pelvic radiotherapy. British journal of cancer. 2005 May 9 [PubMed PMID: 15856043]|
|||Lefevre JH,Amiot A,Joly F,Bretagnol F,Panis Y, Risk of recurrence after surgery for chronic radiation enteritis. The British journal of surgery. 2011 Dec [PubMed PMID: 21928361]|
|||Anwar M,Ahmad S,Akhtar R,Mahmood A,Mahmood S, Antioxidant Supplementation: A Linchpin in Radiation-Induced Enteritis. Technology in cancer research [PubMed PMID: 28532242]|
|||Potten CS,Booth C, The role of radiation-induced and spontaneous apoptosis in the homeostasis of the gastrointestinal epithelium: a brief review. Comparative biochemistry and physiology. Part B, Biochemistry [PubMed PMID: 9467859]|
|||MacNaughton WK, Review article: new insights into the pathogenesis of radiation-induced intestinal dysfunction. Alimentary pharmacology [PubMed PMID: 10792113]|
|||Sauer R,Becker H,Hohenberger W,Rödel C,Wittekind C,Fietkau R,Martus P,Tschmelitsch J,Hager E,Hess CF,Karstens JH,Liersch T,Schmidberger H,Raab R, Preoperative versus postoperative chemoradiotherapy for rectal cancer. The New England journal of medicine. 2004 Oct 21 [PubMed PMID: 15496622]|
|||Huang Y,Guo F,Yao D,Li Y,Li J, Surgery for chronic radiation enteritis: outcome and risk factors. The Journal of surgical research. 2016 Aug [PubMed PMID: 27565069]|
|||Pironi L,Arends J,Bozzetti F,Cuerda C,Gillanders L,Jeppesen PB,Joly F,Kelly D,Lal S,Staun M,Szczepanek K,Van Gossum A,Wanten G,Schneider SM, ESPEN guidelines on chronic intestinal failure in adults. Clinical nutrition (Edinburgh, Scotland). 2016 Apr [PubMed PMID: 26944585]|
|||Bowman LC,Williams R,Sanders M,Ringwald-Smith K,Baker D,Gajjar A, Algorithm for nutritional support: experience of the Metabolic and Infusion Support Service of St. Jude Children's Research Hospital. International journal of cancer. Supplement = Journal international du cancer. Supplement. 1998 [PubMed PMID: 9876485]|
|||Jayapala Reddy V,Sureshkumar S,Vijayakumar C,Amaranathan A,Sudharsanan S,Shyama P,Palanivel C, Concurrent Chemoradiation Affects the Clinical Outcome of Small Bowel Complications Following Pelvic Irradiation: Prospective Observational Study from a Regional Cancer Center. Cureus. 2018 Mar 13 [PubMed PMID: 29755913]|
|||Yang X,Wang J,Lin L,Gao D,Yin L, Concomitant chemoradiotherapy versus pure radiotherapy in locally advanced cervical cancer: a retrospective analysis of complications and clinical outcome. European journal of gynaecological oncology. 2016 Aug [PubMed PMID: 29894074]|