Symptomatic Management of Hormonal Syndromes in NEC

1. Symptomatic Management of Hormonal Syndromes in NEC DariaArbogast CNP, MSN, AOCN, APRN-BC

2. Cardinal carcinoid symptoms are diarrhea and flushing

3. Diarrhea Occurs in 67% to 84% of patients with syndrome: secretory; typically voluminous, watery and post prandial, may be associated with abdominal cramping. (Jensen RT, Doherty GM. Principles and Practice of Oncology. 6th ed. Baltimore, MD: Lippincott, Williams & Wilkins; 2001:1813-1833)

4. Flushing Typically heat and prickly sensation with reddening of face and neck, sometime with associated lacrimation, palpitations and conjunctival redness and edema.

5. Diarrhea management

6. Refractory diarrhea often identified as the primary symptom to negatively impact QOL. (Hogan CM. Oncol Nurs Forum. 1998;25:879-886)

7. Assessment Is the diarrhea new onset or many months duration?

8. Good assessment of diarrhea includes: number of stools per day consistency color presence of blood presence of steatorrhea; appearance of oiliness in the commode water foamy stool that floats on the water unusually strong stool odor

9. Be specific: • How many movements per day • May be 2-30 stools per day • What is ‘normal’ • Consistency of stool • Abdominal pain may accompany diarrhea, but diarrhea may occur alone

10. Stool cultures are never wrong especially when diarrhea is new or the character of the diarrhea is changed. • Assess for rectal irritation when patient has severe diarrhea and suggest products for gentle cleansing and barrier protection. • Use caution with antidiarrheals if patient is at risk for bowel obstruction.

11. Classification of Diarrhea

12. Secretory (endocrine tumors) -intestinal hypersecretion Osmotic (j-tubes, G-tubes) mechanical disturbance, hyperosmotic fluids Exudative (radiation damage) inflammation and ulceration of bowel mucosa Malabsorptive (lactose intolerance) mechanical and biochemical disturbances Dysmotility-associated (irritable bowel syndrome rapid transit of stool through small intestines Chemotherapy-induced (irinotecan, 5FU mechanical and biochemical disturbances resulting from effects of chemotherapy on bowel mucosa

13. Drug therapies for diarrhea

14. Start with low risk, OTC therapies

15. Loperimide is often effective • Loperimide can be taken on scheduled basis determined by stool pattern. • Point out to patients that they should ignore package instructions and follow your suggestions

16. Consider psyllium fiber. While it seems to help in only few cases—it seems worth finding out who those folks are based on low cost and ease of access. Fiber therapy

17. Bile acid binders

18. Colestipol (colestyramine, if dysphagia) or other bile acid binders.  Start 1 gram/day and escalate typically to 3 gm based on response, in rare cases up to 6 gm/day. This may improve consistency if stool is typically watery.

19. Bile acid binders are available for elevated lipids but hard to use in that context due to constipation so can be used for its side effect. • Must be taken at time that no other medications are taken due to binding effect that will inactivate other drugs.

20. Diphenoxylate and atropine, codiene, in rare cases tincture of opium or paregoric slow transit time. • Remember when using these products, avoid use of slow release caustic drugs such as ER potassium. Other gut motility drugs

21. SteatorheaSteatorhea is common with chronic use of octreotide but may occur as part of disease syndrome.

22. Assess for steatorhea symptoms and if present order enzymes • Sometimes effective as single agent in carcinoid and medullary thyroid cancer diarrhea • Most people taking octreotide will eventually require pancrelipase supplement.

23. Prebiotics/Probiotics

24. Prebiotics-nondigestibe food ingredients that stimulate growth/or activity of favorable bacteria (lactobacilli, bifidobacteria) • Probiotics -live microbial nonpathogenic food supplements that survive passage through GI tract (lactobacillus acidophilus, lactobactillus bulgaricus, streptococcus thermophilus • Synbiotics-combinations of both pre and pro biotics (gructooligosaccharides, bifidobacteria)

25. If no history of pancreatitis, routinely suggest probiotics with preference for the multiorganism products (examples are florestor or florajen3). Patients should understand this is not for diarrhea, per se, but to correct the environmental damage to normal bowel flora from chronic diarrhea.

26. Octreotide

27. Diarrhea management may be as simple as scheduled antidiarrheal with perhaps biggest barrier being patient reluctance to take scheduled antidiarrheal---partly because they read the package directions for OTC loperimidedirecting them not to use on scheduled or long term basis and to use AFTER the loose stools. Consider

28. Other options

29. Activated charcoal- OTC but not always in pharmacy stock. Very binding similar to bile acid binders. • Pectin-health food stores, sometimes in combination with fiber product. Very effective for some.

30. Attapulgite-available in Canada, 1200 to 1500 mg with no more than 9000 mg taken in twenty-four hours. • Kaolin-2600 mg, not to exceed more than 26200 mg per 24 hours.

31. Typically try one drug at a time to assess effect. If first option helps but not enough at maximized dose, add 2nd option but don’t stop option #1. Things to remember

32. If more than 3 or 4 drugs needed, consider stopping everything and starting again. • Narcotics may impact diarrhea control so if patient eventually requires narcotics for pain, they may need to revamp diarrhea control program.

33. Flushing

34. Occurs in 23% to 65% of patients initially and 63% to 78% of patients over course of their disease. • Patients may be unaware; direct questioning needed. • (Jenson RT, Doherty GM. Cancer principles & Practice of Oncology. 6th ed. Baltimore, MD: Lippincott, Williams & Wilkins; 2001: 1813-1833.)

35. Two varieties of flushing based on tumor location • Erythema of face and neck associated with midgut tumors • Typically lasts minutes • Forgut associated flushing is more intense event • Can last hours and cause a purplish hue

36. Non Diarrhea Symptom Management

37. A serotonin and histamine antagonist, often effective. Typically 4 mg TID Caution is for sedation; advise taking in afternoon and evening rather than in AM due to sedation. Consider 4 mg between lunch and dinner and 8 mg at bedtime. Cyproheptadine

38. In obese or weight conscience patients, warn that appetite simulation may occur. If appetite stimulation occurs drug can be stopped so worth trying for flushing, rashes, ect.

39. Famotidine will work in a few cases. Famotidine

40. Ondansetron can be dramatically effective in a few cases Ondansetron

41. Very hard to obtain reimbursement due to expense of drug & off label use in this setting. • Often first supply will go through which gives you chance to assess impact. • If you have success then appeals can be made and references are available to validate activity in this setting.

42. Can Diet Modifications help with Carcinoid syndrome?

43. For some patients, yes: • Many have increased diarrhea, flushing when they drink alcoholic beverages or caffeine. • Eating chocolate or spicy foods may increase symptoms. • Large meals may cause syndrome.

44. Dietary exacerbation of symptoms is highly individual. There are no specific food list that applies. Foods restricted for 5HIAA testing are most likely candidates due to impact on serotonin output. • For detailed discussion by Monica Warner: http://www.carcinoid.org/content/nutritional-concerns-carcinoid-patient-developing-nutrition-guidelines-persons-carcinoid-dis

45. Foods containing 5-Hydroxytryptamine (serotonin)

46. Bananas • Pineapple and its juice • Tomatoes and all tomato products • Plums • Eggplant • Avocado • Kiwi • Fruits in general • Nuts, especially walnuts

47. Registered dietician can help provide counseling • Review all written materials or information handed to patients to assure appropriate for their disease process Nutrition Counseling

48. Dietary Guidelines

49. Replace fluid and electrolytes with water or low osmolality fluids • BRAT diet can be used for very short periods of time (1 or 2 days). • Fried or spicy foods may relate to increased syndrome

50. Assure adequate nutritional intake and balance • Alcohol, caffeine and tobacco may irritate bowel • Avoid hyperosmotic supplements • Consider special vitamin and mineral needs and dietary supplements-niacin