Can cancer cause diarrhea, mucosal damage in the intestines, and/or intestinal inflammation?

Cancer Treatment Can Cause Diarrhea, Mucosal Damage, and Intestinal Inflammation

Yes, cancer treatments—particularly chemotherapy, radiotherapy, and biological agents—directly cause diarrhea, intestinal mucosal damage, and inflammation through multiple mechanisms that affect the gastrointestinal tract. 1

Mechanisms of Gastrointestinal Damage

Chemotherapy-Induced Effects

Cytotoxic chemotherapy agents have direct toxic effects on the GI mucosa, causing inflammation, edema, ulceration, and atrophy. 1 The pathophysiology involves:

• Stem cell apoptosis and disrupted cellular renewal lead to histological changes and mucosal inflammation, affecting up to 40-100% of cancer patients receiving chemotherapy 2
• Increased bowel permeability combined with immunosuppression predisposes patients to transmural GI infection, potentially progressing to septicemia and secondary mucosal ischemia 1
• Damage to the mucosa, submucosa, and GI stem cells contributes to both acute and chronic gastrointestinal problems 1

Specific Causes of Diarrhea

Multiple mechanisms contribute to chemotherapy-induced diarrhea 1:

• New-onset lactose intolerance occurs in 10% of patients during 5-fluorouracil chemotherapy 1
• Small bowel bacterial overgrowth is a frequent cause of ongoing GI symptoms including diarrhea, flatulence, bloating, and pain 1
• Bile acid malabsorption and pancreatic insufficiency are important contributory factors 1

Radiotherapy-Induced Damage

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. 1 Key features include:

• Chronic GI dysfunction may arise immediately after acute symptoms or develop de novo months, years, or even decades later 1
• Chemotherapy increases tissue sensitivity to radiation damage, compounding the mucosal injury 1
• Ischemic and fibrotic changes potentially cause long-term impairment of GI physiological functions 1

Biological Agents

Targeted therapies including tyrosine kinase inhibitors, proteasome inhibitors, and anti-angiogenesis agents cause GI toxicity, though the spectrum and mechanisms are poorly defined. 1

Clinical Significance

Severity and Impact

• Diarrhea can be severe and associated with life-threatening dehydration and electrolyte abnormalities, particularly with newer chemotherapy agents 3, 4
• Treatment-induced diarrhea may force dose reductions or treatment discontinuation, compromising anticancer efficacy 2
• Pathologies include ulceration, pain, nausea, diarrhea, and bacterial translocation sepsis 2

Chronic Manifestations

A small proportion of patients develop ongoing GI problems with constipation, diarrhea, flatulence, bloating, and pain that persist after treatment completion. 1 Contributing factors include:

• Cumulative drug dose and degree of immunosuppression during treatment 1
• Degree of damage to mucosa, submucosa, and GI stem cells 1
• Interactions between different cancer treatments complicate the clinical picture 1

Important Clinical Pitfalls

Organic causes for symptoms are frequently missed in cancer patients, leading to ineffective and potentially harmful treatments. 1 Clinicians must:

• Rule out infectious causes (including C. difficile) before initiating symptomatic management, as cancer patients receiving chemoradiation have disrupted GI microflora 5
• Recognize that continuing symptoms may mask early diagnosis of recurrent or second cancers 1
• Understand that cancer treatment can damage the visceral nervous system, leading to GI symptoms through altered autonomic nervous system function 6