What causes yellow stool in a patient after a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure?

Yellow Stool After HIPEC: Causes and Clinical Significance

Yellow stool after HIPEC is most commonly caused by bile salt malabsorption secondary to chemotherapy-induced enteropathy, rapid intestinal transit from postoperative ileus resolution, or fat malabsorption from pancreatic/biliary dysfunction related to the chemotherapy agents used during the procedure.

Primary Mechanisms

Chemotherapy-Induced Enteropathy

• Cisplatin (100 mg/m²) and mitomycin C (30-40 mg/m²), the most common HIPEC agents, directly damage intestinal mucosa and disrupt bile salt reabsorption in the terminal ileum 1, 2
• This leads to bile salt diarrhea with characteristic yellow-green, watery stools that may persist for weeks after the procedure 2
• The hyperthermic component (41-43°C for 60-90 minutes) potentiates mucosal injury beyond what systemic chemotherapy alone would cause 1, 2

Altered Gastrointestinal Transit

• Rapid transit through the small bowel prevents adequate bile salt reabsorption and fat digestion, resulting in steatorrhea with yellow, greasy stools 3
• Post-HIPEC adhesions and altered bowel anatomy from cytoreductive surgery create areas of accelerated transit alternating with partial obstruction 3
• Small bowel obstruction occurs in 19.9% of patients post-HIPEC, with adhesive causes in 57.5% of cases, often presenting with intermittent symptoms including stool color changes 3

Pancreaticobiliary Dysfunction

• Chemotherapy agents used in HIPEC can cause transient pancreatic insufficiency or biliary stasis
• Yellow stool indicates undigested fat (steatorrhea) from inadequate pancreatic enzyme secretion or bile flow

Critical Differential Diagnoses to Exclude

Clostridioides difficile Infection

• C. difficile colitis presents with yellow-white pseudomembranes and must be ruled out with stool testing when yellow diarrhea occurs post-HIPEC 4
• Patients present with abdominal pain, diarrhea, fever, and leukocytosis—symptoms that overlap with expected post-HIPEC complications 4
• Empiric antibiotic treatment should be initiated while awaiting stool test results if clinical suspicion is high 4

Encapsulating Peritoneal Sclerosis (EPS)

• EPS is a rare but serious complication of HIPEC that presents with intestinal obstruction and can alter stool characteristics 5
• Median time to presentation is 15 months postoperatively, with CT showing dilated small intestine enveloped by thickened membrane 5
• Consider EPS when intestinal symptoms fail to improve with conservative management and peritoneal cancer recurrence is excluded 5

Malignant Bowel Obstruction

• 42.5% of post-HIPEC bowel obstructions are malignant in origin, occurring at median 7.7 months postoperatively 3
• These patients demonstrate decreased overall survival compared to those with adhesive obstruction 3
• Yellow stool may represent overflow diarrhea around a partial obstruction

Immediate Clinical Assessment

Red Flag Symptoms Requiring Urgent Evaluation

• Fever >38.5°C, increasing abdominal pain, or signs of sepsis mandate immediate medical evaluation 6
• Decreased urine output or dark urine suggests renal dysfunction from cisplatin toxicity (occurs in 15% vs 4% in controls) 6
• Purulent drainage from incisions or signs of anastomotic leak 6

Laboratory Monitoring

• Arrange follow-up testing within 7-10 days to monitor renal function and hemoglobin, as anemia occurs in 67% vs 50% in controls 6
• Stool studies for C. difficile toxin, fecal fat, and fecal elastase if steatorrhea is suspected
• Complete metabolic panel to assess for electrolyte derangements from diarrhea

Management Algorithm

Conservative Management (First-Line)

• Maintain oral fluid intake of at least 2 liters daily and monitor for dehydration signs 6
• Olanzapine 5-10 mg PO daily for breakthrough nausea/vomiting associated with yellow diarrhea 1, 6
• Bile acid sequestrants (cholestyramine 4g TID) if bile salt malabsorption is confirmed
• Pancreatic enzyme replacement if steatorrhea persists beyond 2-3 weeks

Escalation Criteria

• If symptoms persist despite conservative treatment and C. difficile testing is negative, early gastroenterology consultation and lower endoscopy are indicated 4
• Surgical intervention is required in 28.7% of patients with post-HIPEC bowel obstruction 3
• CT imaging to evaluate for EPS, malignant obstruction, or intra-abdominal collection (which occurs more frequently with surgical site infection) 3

Common Pitfalls to Avoid

• Do not dismiss yellow stool as "expected" without ruling out C. difficile infection, especially given the high rate of postoperative complications (27% grade 3-4 toxicities) 1, 4
• Do not delay imaging if conservative management fails, as malignant bowel obstruction requires different management than adhesive obstruction 3
• Do not attribute all GI symptoms to chemotherapy without considering surgical complications like anastomotic leak or collection, which are associated with worse outcomes 3
• Recognize that mitomycin C is independently associated with worse obstruction-free survival (HR 2.9), making GI complications more likely with this agent 3

Impact on Adjuvant Therapy

• Patients must complete minimum 3 cycles (preferably 6 total) of systemic chemotherapy despite delayed initiation after HIPEC 1, 6
• Yellow stool and associated malabsorption may affect oral chemotherapy absorption (e.g., S-1, capecitabine)
• Oncology follow-up within 2-3 weeks of discharge is essential to coordinate adjuvant therapy timing 6