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Diarrhea in Cancer Patients

Diarrhea in Cancer Patients. By. Abdallah H. Elsheref. Diarrhea. WHO Definition: The passage of more than 3 unformed stools in 24 hours. Or Frequent passage of loose stools with urgency. NCI Grading of Diarrhea. Causes of diarrhea in cancer paients. Chemotherapy induced diarrhea

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Diarrhea in Cancer Patients

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  1. Diarrhea in Cancer Patients By Abdallah H. Elsheref

  2. Diarrhea WHO Definition: The passage of more than 3 unformed stools in 24 hours. Or Frequent passage of loose stools with urgency.

  3. NCI Grading of Diarrhea

  4. Causes of diarrhea in cancer paients • Chemotherapy induced diarrhea • Infectious diarrhea • Entral feeding • Celiac plexus block • Radiotherapy induced diarrhea • Paraneoplastic syndrome

  5. Chemotherapy induced diarrhea • The most common CTh agents causing diarrhea are: • 5 Flu • Capecitabine • Irinotecan • Taxanes • Target agents“ Sunitinib, Sorafanib, Erlotinib, Gefitinib ….”

  6. 5- Fluorouracil • Mechanism of action: • 5- FLUOROURACIL decrease the biosynthesis of pyrimidine nucleotides by inhibiting thymidylate synthase, the enzyme that catalyzes the rate limiting step in DNA synthesis. • Leucovorin increases binding of 5-FU to thymidylate synthase thereby increasing 5-FU t1/2

  7. 5- Fluorouracil • Mechanism of Diarrhea with 5 Flu: 5-Flu causes mitotic arrest of intestinal crypts cells Increase in the ratio of immature secretory crypt cells to mature villous enterocytes Abnormal secretion of electrolytes and fluids Diarrhea

  8. 5- Fluorouracil • Risk factors • Older age • Coadministration with Leucovorin • Bolus rather than infusion • Associated bowel disease • Female gender

  9. DPD deficiency

  10. DPD deficiency • Life-threatening complication including: • Sever diarrhea • Sever mucositis • Pancytopenia

  11. Capecitabine “Xeloda” • Capecitabine, a precursor of 5-FU, is an oral fluoropyrimidine cytotoxic agent developed with the aim of providing a more effective , less toxic and oral drug. • It is converted in vivo to 5-FU • The prevelance of diarrhea is 30% - 40%.

  12. Irinotecan “Campto” • Topoisomerase I inhipitor (Topoisomerase I relaxes the supercoiled DNA for variety of cellular processes) • 2 Types of diarrhea may occur: • Acute diarrhea(immediately after drug administration and usually respond to atropine) • Delayed diarrhea(24 hrs after drug administration)

  13. Irinotecan “Campto”cont. • Mechanism of diarrhea: Destructive effect of active agent on the intestinal colonic Epithelium + Production of pro-inflammatory cytokines Disturbance in absorptive and secretory functions of mucosa Diarrhea

  14. Assessment • History and physical examination: ( Don’t forget Vital signs and signs of dehydration) • Dietary history and medical history • Grading of diarrhea

  15. Assessment cont. • Complete lab. • CBC • RFT • LFT • Bl. Sugar ( Don’t forget Electrolytes) • Stool analysis • Blood culture if patient feverish • Imaging according to patient complaint

  16. General principles in the management of CTH induced diarrhea • Rule out other causes of diarrhea • Diet Modification: e.g. * Increase Fluid intake * Fresh diet • Anti-diarrheal medications

  17. Anti-diarrheal medications • Loperamide Mech: • Reduces stool frequency • Decrease bowel movement Dose: 4 mg followed by 2mg every 2-4 hrs or after every unformed stool (up to 16 mg /day)

  18. Anti-diarrheal medications cont. • Atropine – diphenoxylate “Lomotile” Dose: 1-2 tablets every 4-6 hours

  19. Anti-diarrheal medications cont. • Octreotide “Sandostatine” Mech: • Somatostatine analogue • Suppression insulin, glucagone, VAIP and pancreatic exocrine function • Suppress intestinal motility Dose: 100 – 150 mcg SC/IV 3 times /day “up to 500 mcg /day” according to response

  20. How to manage ?

  21. Grade 1-2 Diarrhea Dietary management Loperamide 4mg then 2mg after loose stool (max 16 mg /day) Diarrhea resolved Adjust diet and Stop loperamide after 12 hrs without diarrhea Not resolved High dose loperamide 4mg then 2mg/2hrs Not resolved after 24 hrs Octeroides 100 – 150 mcg + Fulid and elect. reeplacement

  22. Grade 3-4 Diarrhea Hospital admition And Loperamide 4mg then 2mg after loose stool (max 16 mg /day) Octeroide 100 – 150 mcg Fluid and elect. Replacement + Consider antibiotic + Not resolved after 24 hrs Increase Octeroide up to 500 mcg / day or 25-50 mcg/hr continuous infusion + High dose loperamide

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