Gastrointestinal Damage from Cancer Treatment

Mechanisms of Damage

Cancer treatments, including chemotherapy, radiotherapy, and biological agents, directly cause diarrhea, intestinal mucosal damage, and inflammation through multiple mechanisms that affect the gastrointestinal tract, according to the American Gastroenterological Association 1, 2
Cytotoxic chemotherapy agents have direct toxic effects on the GI mucosa, causing inflammation, edema, ulceration, and atrophy, as reported by the European Society for Medical Oncology 1, 2
Increased bowel permeability combined with immunosuppression predisposes patients to transmural GI infection, potentially progressing to septicemia and secondary mucosal ischemia, as noted by the American College of Gastroenterology 1, 2
Damage to the mucosa, submucosa, and GI stem cells contributes to both acute and chronic gastrointestinal problems, according to the National Comprehensive Cancer Network 3, 4

New-onset lactose intolerance occurs in 10% of patients during 5-fluorouracil chemotherapy, as reported by the American Society of Clinical Oncology 1, 2
Small bowel bacterial overgrowth is a frequent cause of ongoing GI symptoms including diarrhea, flatulence, bloating, and pain, according to the European Society for Medical Oncology 3, 4
Bile acid malabsorption and pancreatic insufficiency are important contributory factors, as noted by the American Gastroenterological Association 1, 2

Radiotherapy initially causes mucosal inflammation or cell death, followed by persistent cytokine activation in the submucosa leading to progressive ischemia, fibrosis, and loss of stem cells, as reported by the American Society for Radiation Oncology 2, 4
Chronic GI dysfunction may arise immediately after acute symptoms or develop de novo months, years, or even decades later, according to the National Comprehensive Cancer Network 2, 4
Chemotherapy increases tissue sensitivity to radiation damage, compounding the mucosal injury, as noted by the European Society for Medical Oncology 2, 4

A small proportion of patients develop ongoing GI problems with constipation, diarrhea, flatulence, bloating, and pain that persist after treatment completion, as reported by the American College of Gastroenterology 3, 4
Cumulative drug dose and degree of immunosuppression during treatment contribute to chronic GI problems, according to the National Comprehensive Cancer Network 3, 4
Degree of damage to mucosa, submucosa, and GI stem cells contributes to chronic GI problems, as noted by the American Gastroenterological Association 3, 4

Clinicians must rule out infectious causes (including C. difficile) before initiating symptomatic management, as cancer patients receiving chemoradiation have disrupted GI microflora, as recommended by the Infectious Diseases Society of America 5
Continuing symptoms may mask early diagnosis of recurrent or second cancers, as reported by the American Cancer Society 1
Cancer treatment can damage the visceral nervous system, leading to GI symptoms through altered autonomic nervous system function, according to the American Autonomic Society 6

Chemotherapy causes direct mucosal damage through multiple pathways that result in edema, inflammation, ulceration, and atrophy of the intestinal lining, leading to increased bowel permeability and immunosuppression 7, 8, 9
Direct cytotoxic effects on rapidly dividing GI mucosal cells lead to inflammation and edema as primary manifestations, according to the American Gastroenterological Association 7, 8

5-fluorouracil/capecitabine causes intestinal edema and inflammation, with 10% of patients developing new-onset lactose intolerance, as reported by the National Comprehensive Cancer Network 7
Oxaliplatin-based regimens can cause severe hepatic complications in addition to intestinal toxicity, as noted by the European Society for Medical Oncology 7

A small proportion of patients develop chronic GI problems including persistent edema, with small bowel bacterial overgrowth being a frequent cause of ongoing symptoms, according to the American College of Gastroenterology 7, 8
Cumulative chemotherapy dose and degree of immunosuppression during treatment contribute to chronicity, as reported by the National Cancer Institute 7, 8