Table 5. Digestive Tract Late Effects
|Predisposing Therapy||Gastrointestinal Effects||Health Screening/Interventions|
|GVHD = graft-versus-host disease; KUB = kidneys, ureter, bladder (plain abdominal radiograph).|
|Radiation impacting esophagus; hematopoietic cell transplantation with any history of chronic GVHD||Esophageal stricture||History: dysphagia, heart burn|
|Esophageal dilation, antireflux surgery|
|Radiation impacting bowel||Chronic enterocolitis; fistula; strictures||History: nausea, vomiting, abdominal pain, diarrhea|
|Serum protein and albumin levels yearly in patients with chronic diarrhea or fistula|
|Surgical and/or gastroenterology consultation for symptomatic patients|
|Radiation impacting bowel; laparotomy||Bowel obstruction||History: abdominal pain, distention, vomiting, constipation|
|Exam: tenderness, abdominal guarding, distension (acute episode)|
|Obtain KUB in patients with clinical symptoms of obstruction|
|Surgical consultation in patients unresponsive to medical management|
|Pelvic surgery; cystectomy||Fecal incontinence||History: chronic constipation, fecal soiling|
Hepatic complications resulting from childhood cancer therapy are uncommon and observed primarily as acute treatment toxicities. Recipients of HSCT are the exception to this rule as these individuals frequently experience chronic liver dysfunction related to microvascular, immunologic, infectious, metabolic, and toxic etiologies. Chemotherapeutic agents with established hepatotoxic potential include antimetabolite agents like 6-mercaptopurine, 6-thioguanine, methotrexate, and rarely, dactinomycin. Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) and cholestatic disease have been observed after thiopurine administration, especially 6-thioguanine. Progressive fibrosis and portal hypertension has been reported in a subset of children who developed VOD/SOS following treatment with 6-thioguanine.[31,32,33] Acute, dose-related, reversible VOD/SOS has been observed in children treated with dactinomycin for pediatric solid tumors.[34,35] In the transplant setting, VOD/SOS has also been observed following conditioning regimens that have included cyclophosphamide/TBI, busulfan/cyclophosphamide and carmustine/cyclophosphamide/etoposide. Because high-dose cyclophosphamide is common to all of these regimens, toxic cyclophosphamide metabolites resulting from the agent's variable metabolism have been speculated as a causative factor.
Acute radiation-induced liver disease also causes endothelial cell injury that is characteristic of VOD/SOS. In adults, the whole liver has tolerance up to 30 Gy to 35 Gy with conventional fractionation, the prevalence of radiation-induced liver disease varies from 6% to 66% based on the volume of liver involved and on hepatic reserve.[37,38] Based on limited data from pediatric cohorts treated in the 1970s and 1980s, persistent radiation hepatopathy after contemporary treatment appears to be uncommon in long-term survivors without predisposing conditions such as viral hepatitis or iron overload. The risk of injury in children increases with radiation dose, hepatic volume, younger age at treatment, prior partial hepatectomy, and concomitant use of radiomimetic chemotherapy like dactinomycin and doxorubicin.[40,41,42,43] Survivors who received radiation doses of 40 Gy to at least one-third of liver volume, doses of 30 Gy or more to whole abdomen, or an upper abdominal field involving the entire liver are at highest risk for hepatic dysfunction.