Surviving Childhood Cancer Increases GI Risks

Individuals who received therapy for cancer during childhood have an increased risk of developing GI complications later in life, according to Robert Goldsby et al. in the May issue of Gastroenterology.

About 80% of children who receive cancer therapy survive more than 5 years; therapies can be especially toxic to the GI tract and liver, but their long-term consequences have not been determined. Goldsby et al. analyzed data from the Childhood Cancer Survivor Study (CCSS)—a study of 14,358 survivors of childhood cancer who were diagnosed between 1970 and 1986—to identify those that developed upper or lower GI or liver conditions; data were compared with those from siblings. The main therapies the children received were chemotherapy (81%), abdominal radiation, or abdominal surgery. The types of cancers they were treated for included leukemia or lymphoma (54.6%), bone or soft tissue sarcomas (16%), brain tumors (13.1%), kidney tumors (8.7%) and neuroblastomas (6.6%).

More than 40% of childhood cancer survivors reported a GI complication within 20 years after cancer therapy. Upper GI complications such as heartburn and indigestion were most common, with a cumulative incidence of 25.8% at 20 years, followed by lower GI complications such as constipation (15.5%), and liver conditions such as gallbladder disease or cirrhosis (9.4%).

Cumulative incidence of GI conditions (any, red; 2 or more, black) among 5-year survivors.

Cancer therapy causes acute GI toxicities, including nausea, vomiting, esophagitis, mucositis, enteritis, diarrhea and liver dysfunction. Experiencing these symptoms could increase patient sensitivity, but cancer treatments also cause direct damage; chemotherapy causes repeated injury and scarring of GI tissues, and GI infections can result from the related myelosuppression. Radiation can cause mucosal inflammation, dysmotility and vascular injury that leads to intestinal ischemia and fibrosis; it can also damage abdominal blood vessels and liver tissue. Surgery can result in anastomotic strictures or bowel obstruction from adhesions.

Goldsby et al. observed, as they expected, that abdominal radiation increased the risk of upper and lower GI complications. However, it did not increase the risk of liver complications. They propose this reflects the fact that most patients that received abdominal radiation (for neuroblastoma or Wilms tumor) had the liver spared from direct and/or high doses of radiation. Patients undergoing bone marrow transplantation with total body irradiation did have a high rate of liver conditions.

In an accompanying editorial, Mark Lowe and Robert Noll add that more information is needed about rates of Hepatitis C virus infection in this population, because the cohort dates to a time when patients could be infected via blood transfusions. Acquiring these types of infections during treatment could increase the incidence of liver disease in this cohort, compared with patients treated more recently.

Although many studies based on the data from the CCSS have been published, the report by Goldsby et al is the first to focus on gastrointestinal complications in survivors of childhood cancer.

Lowe and Noll point out that because about 1 in 640 US adults are survivors of childhood cancers, gastroenterologists are likely to see these patients in their practice. Better knowledge about the pathophysiology of the GI diseases in childhood cancer survivors could improve our understanding of the GI response to injury.

More Information on the CCSS:

Read the article online.
Goldsby R, Chen Y, Raber S, et al. Survivors of childhood cancer have increased risk of gastrointestinal complications later in life. Gastroenterology 2011;140:1464–1471.e1.

Read the accompanying editorial.
Lowe ME, Noll RB. Childhood cancer survival: a risk factor for GI disease. Gastroenterology 2011;140:1383–1386.


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About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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