A 64-year-old man comes to the office for the evaluation of new-onset diarrhea. He has noted 6-8 watery, brown stools every day for the past 2 weeks. There have been frequent nocturnal episodes of diarrhea, obliging the patient to wear a diaper while sleeping. He reports no bulky, foul-smelling stools or melena, hematochezia, or abdominal pain. The patient was recently diagnosed with metastatic pancreatic adenocarcinoma and began chemotherapy 4 weeks ago. He has had no sick contacts or recent travel. The patient is afebrile and vital signs are stable. The abdomen is soft and nontender. Rectal examination reveals brown, nonbloody stool. Laboratory studies are as follows: Stool tests are negative for fecal occult blood and Clostridioides (formerly Clostridium) difficile. Which of the following pharmacologic agents would be most beneficial for this patient?

Question

A 64-year-old man comes to the office for the evaluation of new-onset diarrhea.  He has noted 6-8 watery, brown stools every day for the past 2 weeks.  There have been frequent nocturnal episodes of diarrhea, obliging the patient to wear a diaper while sleeping.  He reports no bulky, foul-smelling stools or melena, hematochezia, or abdominal pain.  The patient was recently diagnosed with metastatic pancreatic adenocarcinoma and began chemotherapy 4 weeks ago.  He has had no sick contacts or recent travel.  The patient is afebrile and vital signs are stable.  The abdomen is soft and nontender.  Rectal examination reveals brown, nonbloody stool.  Laboratory studies are as follows:  Stool tests are negative for fecal occult blood and Clostridioides (formerly Clostridium) difficile.  Which of the following pharmacologic agents would be most beneficial for this patient?

Quizplus · Accepted Answer

This patient has watery diarrhea that developed after beginning chemotherapy. In association with a normal complete blood count and negative tests for Clostridioides difficile and fecal occult blood, this presentation is consistent with chemotherapy-related diarrhea (CRD). Many chemotherapeutic agents (eg, fluorouracil and irinotecan-both of which are used to treat metastatic pancreatic cancer) exert a direct cytotoxic effect on intestinal mucosa, resulting in decreased fluid absorption and increased electrolyte secretion. As with this patient, CRD often results in secretory diarrhea, which is voluminous, watery, and persistent despite periods of fasting (eg, nocturnal diarrhea). Osmotic diarrhea, which occurs only after eating, may also occur due to damage of the brush border enzyme system (eg, lactase deficiency causing lactose intolerance). Management of CRD includes oral hydration and antidiarrheal therapy with loperamide or diphenoxylate-atropine. Severe diarrhea may warrant hospital admission for intravenous fluid and electrolyte repletion. Because chemotherapy is a risk factor for infection (particularly with C difficile), all patients with persistent diarrhea should undergo laboratory evaluation (eg, complete blood count, serum chemistry) and stool testing (eg, C difficile stool studies, fecal occult blood) prior to a presumptive diagnosis of CRD. (Choice A) Cholestyramine is sometimes used to treat chronic diarrhea related to bile acid malabsorption, which can also cause secretory diarrhea. However, it typically occurs after surgical resection of the small bowel or gallbladder. Although bile acid malabsorption can occasionally develop as a side effect of chemotherapy (eg, due to ileal damage), a trial of loperamide is typically the initial step in CRD management; if chronic diarrhea persists, further evaluation for bile acid malabsorption or empiric treatment with cholestyramine can be considered. (Choice C) Metronidazole, followed by paromomycin, is used to treat intestinal amebiasis, which causes bloody diarrhea, fever, and abdominal pain. It typically occurs after travel to an endemic area (eg, Central America). (Choice D) Pancrelipase is used to treat steatorrhea due to pancreatic exocrine insufficiency, which usually is caused by chronic pancreatitis. Although exocrine insufficiency may rarely occur in those with pancreatic cancer, steatorrhea (ie, bulky diarrhea with visible fat globules) would be expected. (Choices E and F) Both prednisone and sulfasalazine are used to treat inflammatory bowel disease (eg, ulcerative colitis). However, inflammatory bowel diseases typically causes abdominal pain, hematochezia, anemia, and leukocytosis. Educational objective: Chemotherapy-related diarrhea often presents with voluminous, watery, brown stool that persists despite periods of fasting (eg, nocturnal diarrhea). Evaluation includes complete blood count, serum chemistry, and stool studies (eg, Clostridioides difficile, fecal occult blood) to rule out other etiologies. First-line therapy is oral hydration and antidiarrheal medications (eg, loperamide).

A 64-Year-Old Man Comes to the Office for the Evaluation