Radiation enteropathy

Radiation enteropathy is a syndrome that may develop following abdominal or pelvic radiation therapy for cancer.[1][2] Many affected people are cancer survivors who had treatment for cervical cancer or prostate cancer; it has also been termed pelvic radiation disease with radiation proctitis being one of the principal features.[3]

Radiation enteropathy
Other namesRadiation enteritis, pelvic radiation disease
SpecialtyGastroenterology, surgery, oncology

Signs and symptoms

People who have been treated with radiotherapy for pelvic and other abdominal cancers frequently develop gastrointestinal symptoms.[2][3] These include:

Gastrointestinal symptoms are often found together with those in other systems including genitourinary disorders and sexual dysfunction. The burden of symptoms substantially impairs the patients' quality of life.

Nausea, vomiting, fatigue and diarrhea may happen early during the course of radiotherapy. Radiation enteropathy represents the longer-term, chronic effects which may be found after a latent period most commonly of 6 months to 3 years after the end of treatment. In some cases, it does not become a problem for 20–30 years after successful curative therapy.[1]

Associated conditions

Causes

A large number of people receive abdominal and or pelvic radiotherapy as part of their cancer treatment with 60–80% experiencing gastrointestinal symptoms.[1] This is used in standard therapeutic regimens for cervical cancer, prostate cancer, rectal cancer, anal cancer, lymphoma and other abdominal malignancies. Symptoms can be made worse by the effects of surgery, chemotherapy or other drugs given to treat the cancer.[4] Improved methods of radiotherapy have reduced the exposure of non-involved tissues to radiation, concentrating the effects on the cancer. However, as the parts of the intestine such as the ileum and the rectum are immediately adjacent to the cancers, it is impossible to avoid some radiation effects.[1] Previous intestinal surgery, obesity, diabetes, tobacco smoking and vascular disorders increase the chances of developing enteropathy.[1]

Pathology

Acute intestinal injury
See also: Acute radiation syndrome

Early radiation enteropathy is very common during or immediately after the course of radiotherapy. This involves cell death, mucosal inflammation and epithelial barrier dysfunction. This injury is termed mucositis and results in symptoms of nausea, vomiting, fatigue, diarrhea and abdominal pain.[1][5] It recovers within a few weeks or months.

Long-term effects of radiation

The delayed effects, found 3 months or more after radiation therapy, produce pathology which includes intestinal epithelial mucosal atrophy, vascular sclerosis, and progressive fibrosis of the intestinal wall, among other changes in intestinal neuroendocrine and immune cells and in the gut microbiota.[1][5] These changes may produce dysmotility, strictures, malabsorption and bleeding. Problems in the terminal ileum and rectum predominate.

Diagnosis

Multiple disorders are found in patients with radiation enteropathy, so guidance including an algorithmic approach to their investigation has been developed.[4][6] This includes a holistic assessment with investigations including endoscopies, breath tests and other nutritional and gastrointestinal tests. Full investigation is important as many cancer survivors of radiation therapy develop other causes for their symptoms such as colonic polyps, diverticular disease or hemorrhoids.[7]

Prevention
See also: Radiation therapy

Prevention of radiation injury to the small bowel is a key aim of techniques such as brachytherapy, field size, multiple field arrangements, conformal radiotherapy techniques and intensity-modulated radiotherapy. Medications including ACE inhibitors, statins and probiotics have also been studied and reviewed.[2][8]

Treatment

In people presenting with symptoms compatible with radiation enteropathy, the initial step is to identify what is responsible for causing the symptoms. Management is best with a multidisciplinary team including gastroenterologists, nurses, dietitians, surgeons and others.[1]

Medical treatments include the use of hyperbaric oxygen which has beneficial effects in radiation proctitis or anal damage.[9] Nutritional therapies include treatments directed at specific malabsorptive disorders such as low fat diets and vitamin B12 or vitamin D supplements, together with bile acid sequestrants for bile acid diarrhea and possibly antibiotics for small intestinal bacterial overgrowth.[2] Probiotics have all been suggested as another therapeutic avenue.[10]

Endoscopic therapies including argon plasma coagulation have been used for bleeding telangiectasia in radiation proctitis and at other intestinal sites, although there is a rick of perforation.[2] Sucralfate enemas look promising in proctitis.

Surgical treatment may be needed for intestinal obstruction, fistulae, or perforation, which can happen in more severe cases.[11] These can be fatal if patients present as an emergency, but with improved radiotherapy techniques are now less common.

A systematic review has found there is some promising evidence for non-surgical interventions for late rectal damage, however due to low quality evidence no conclusions could be drawn.[12]

Optimal treatment usually produces significant improvements in quality of life.[3]

Prevalence

An increasing number of people are now surviving cancer, with improved treatments producing cure of the malignancy (cancer survivors). There are now over 14 million such people in the US, and this figure is expected to increase to 18 million by 2022.[13] More than half are survivors of abdominal or pelvic cancers, with about 300,000 people receiving abdominal and pelvic radiation each year. It has been estimated there are 1.6 million people in the US with post-radiation intestinal dysfunction, a greater number than those with inflammatory bowel disease such as Crohn's disease or ulcerative colitis.[1]

Research

New agents have been identified in animal studies that may have effects on intestinal radiation injury.[1] The research approach in humans has been reviewed.[14]

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References
  1. Hauer-Jensen M, Denham JW, Andreyev HJ (2014). "Radiation enteropathy--pathogenesis, treatment and prevention". Nat Rev Gastroenterol Hepatol. 11 (8): 470–9. doi:10.1038/nrgastro.2014.46. PMC 4346191. PMID 24686268.
  2. Stacey R, Green JT (2014). "Radiation-induced small bowel disease: latest developments and clinical guidance". Ther Adv Chronic Dis. 5 (1): 15–29. doi:10.1177/2040622313510730. PMC 3871275. PMID 24381725.
  3. Fuccio L, Guido A, Andreyev HJ (2012). "Management of intestinal complications in patients with pelvic radiation disease". Clin. Gastroenterol. Hepatol. 10 (12): 1326–1334.e4. doi:10.1016/j.cgh.2012.07.017. PMID 22858731.
  4. Andreyev HJ, Davidson SE, Gillespie C, Allum WH, Swarbrick E (2012). "Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer". Gut. 61 (2): 179–92. doi:10.1136/gutjnl-2011-300563. PMC 3245898. PMID 22057051.
  5. Carr KE (2001). "Effects of radiation damage on intestinal morphology". Int. Rev. Cytol. International Review of Cytology. 208: 1–119. doi:10.1016/s0074-7696(01)08002-0. ISBN 9780123646125. PMID 11510566.
  6. Andreyev HJ, Muls AC, Norton C, Ralph C, Watson L, Shaw C, Lindsay JO (2015). "Guidance: The practical management of the gastrointestinal symptoms of pelvic radiation disease". Frontline Gastroenterol. 6 (1): 53–72. doi:10.1136/flgastro-2014-100468. PMC 4283714. PMID 25580207.
  7. Min M, Chua B, Guttner Y, Abraham N, Aherne NJ, Hoffmann M, McKay MJ, Shakespeare TP (2014). "Is "pelvic radiation disease" always the cause of bowel symptoms following prostate cancer intensity-modulated radiotherapy?". Radiother Oncol. 110 (2): 278–83. doi:10.1016/j.radonc.2013.11.012. PMID 24412017.
  8. Gibson RJ, Keefe DM, Lalla RV, Bateman E, Blijlevens N, Fijlstra M, King EE, Stringer AM, van der Velden WJ, Yazbeck R, Elad S, Bowen JM (2013). "Systematic review of agents for the management of gastrointestinal mucositis in cancer patients". Support Care Cancer. 21 (1): 313–26. doi:10.1007/s00520-012-1644-z. PMID 23142924.
  9. Bennett, Michael H.; Feldmeier, John; Hampson, Neil B.; Smee, Robert; Milross, Christopher (2016-04-28). "Hyperbaric oxygen therapy for late radiation tissue injury". The Cochrane Database of Systematic Reviews. 4: CD005005. doi:10.1002/14651858.CD005005.pub4. ISSN 1469-493X. PMC 6457778. PMID 27123955.
  10. Hamad, Adeel; Fragkos, Konstantinos C.; Forbes, Alastair (2013). "A systematic review and meta-analysis of probiotics for the management of radiation induced bowel disease". Clinical Nutrition. 32 (3): 353–360. doi:10.1016/j.clnu.2013.02.004. PMID 23453637.
  11. Regimbeau JM, Panis Y, Gouzi JL, Fagniez PL (2001). "Operative and long term results after surgery for chronic radiation enteritis". Am. J. Surg. 182 (3): 237–42. doi:10.1016/s0002-9610(01)00705-x. PMID 11587684.
  12. van de Wetering, Fleur T; Verleye, Leen; Andreyev, H. Jervoise N; Maher, Jane; Vlayen, Joan; Pieters, Bradley R; van Tienhoven, Geertjan; Scholten, Rob JPM (2016-04-25). "Non-surgical interventions for late rectal problems (proctopathy) of radiotherapy in people who have received radiotherapy to the pelvis". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd003455.pub2. ISSN 1465-1858. PMC 7173735.
  13. Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, Lin C, Leach C, Cannady RS, Cho H, Scoppa S, Hachey M, Kirch R, Jemal A, Ward E (2012). "Cancer treatment and survivorship statistics, 2012". CA Cancer J Clin. 62 (4): 220–41. doi:10.3322/caac.21149. PMID 22700443.
  14. Movsas B, Vikram B, Hauer-Jensen M, Moulder JE, Basch E, Brown SL, Kachnic LA, Dicker AP, Coleman CN, Okunieff P (2011). "Decreasing the adverse effects of cancer therapy: National Cancer Institute guidance for the clinical development of radiation injury mitigators". Clin. Cancer Res. 17 (2): 222–8. doi:10.1158/1078-0432.CCR-10-1402. PMID 21047979.
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