Advertisement

Stress Ulcer Prophylaxis in the Critically Ill Oncology Population

  • Reagan D. CollinsEmail author
Reference work entry

Abstract

Stress-related mucosal disease in the critically ill population can lead to clinically important gastrointestinal bleeding. Common risk factors for the development of clinically important bleeding include invasive mechanical ventilation for greater than 48 h, coagulopathy, and multiorgan failure. Gastric acid suppression with proton pump inhibitors or histamine-2 receptor antagonists are commonly prescribed in intensive care units for stress ulcer prophylaxis. However, use of stress ulcer prophylaxis is not without risk and has been associated with Clostridium difficile infection and pneumonia. Factors inherent to malignancy and/or treatment may pose additional risk for clinically important bleeding as well as infection in the critically ill oncology population. This chapter will provide an evidence-based review of stress ulcer prophylaxis as well as considerations in the critically ill oncology population.

Keywords

Stress ulcer prophylaxis Proton pump inhibitor Histamine-2 receptor antagonist Critically ill Oncology 

References

  1. 1.
    Alhazzani W, Alenezi F, Jaeschke RZ, Moayyedi P, Cook DJ. Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis. Crit Care Med. 2013;41(3):693–705.  https://doi.org/10.1097/CCM.0b013e3182758734.CrossRefPubMedGoogle Scholar
  2. 2.
    Alhazzani W, Alshamsi F, Belley-Cote E, Heels-Ansdell D, Brignardello-Petersen R, Alquraini M, Perner A, Moller MH, Krag M, Almenawer S, Rochwerg B, Dionne J, Jaeschke R, Alshahrani M, Deane A, Perri D, Thebane L, Al-Omari A, Finfer S, Cook D, Guyatt G. Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials. Intensive Care Med. 2018;44(1):1–11.  https://doi.org/10.1007/s00134-017-5005-8.CrossRefPubMedGoogle Scholar
  3. 3.
    Alhazzani W, Guyatt G, Alshahrani M, Deane AM, Marshall JC, Hall R, Muscedere J, English SW, Lauzier F, Thabane L, Arabi YM, Karachi T, Rochwerg B, Finfer S, Daneman N, Alshamsi F, Zytaruk N, Heel-Ansdell D, Cook D. Withholding Pantoprazole for Stress Ulcer Prophylaxis in critically Ill patients: a pilot randomized clinical trial and meta-analysis. Crit Care Med. 2017;45(7):1121–9.  https://doi.org/10.1097/ccm.0000000000002461.CrossRefPubMedGoogle Scholar
  4. 4.
    Alshamsi F, Belley-Cote E, Cook D, Almenawer SA, Alqahtani Z, Perri D, Thabane L, Al-Omari A, Lewis K, Guyatt G, Alhazzani W. Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care (London). 2016;20(1):120.  https://doi.org/10.1186/s13054-016-1305-6.CrossRefGoogle Scholar
  5. 5.
    ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm. 1999;56(4):347–79.CrossRefGoogle Scholar
  6. 6.
    Avvisati G, Tirindelli MC, Annibali O. Thrombocytopenia and hemorrhagic risk in cancer patients. Crit Rev Oncol Hematol. 2003;48(Suppl):S13–6.CrossRefGoogle Scholar
  7. 7.
    Azab M, Doo L, Doo DH, Elmofti Y, Ahmed M, Cadavona JJ, Liu XB, Shafi A, Joo MK, Yoo JW. Comparison of the Hospital-Acquired Clostridium difficile infection risk of using proton pump inhibitors versus histamine-2 receptor antagonists for prophylaxis and treatment of stress ulcers: a systematic review and meta-analysis. Gut Liver. 2017;11(6):781–8.  https://doi.org/10.5009/gnl16568.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Barkun AN, Bardou M, Pham CQ, Martel M. Proton pump inhibitors vs. histamine 2 receptor antagonists for stress-related mucosal bleeding prophylaxis in critically ill patients: a meta-analysis. Am J Gastroenterol. 2012;107(4):507–20; quiz 521.  https://doi.org/10.1038/ajg.2011.474.CrossRefPubMedGoogle Scholar
  9. 9.
    Barletta JF, Bruno JJ, Buckley MS, Cook DJ. Stress Ulcer Prophylaxis. Crit Care Med. 2016;44(7):1395–405.  https://doi.org/10.1097/ccm.0000000000001872.CrossRefPubMedGoogle Scholar
  10. 10.
    Barletta JF, Sclar DA. Proton pump inhibitors increase the risk for hospital-acquired Clostridium difficile infection in critically ill patients. Crit Care (London). 2014;18(6):714.  https://doi.org/10.1186/s13054-014-0714-7.CrossRefGoogle Scholar
  11. 11.
    Bartlett JG. Historical perspectives on studies of Clostridium difficile and C. difficile infection. Clin Infect Dis. 2008;1:S4–11.  https://doi.org/10.1086/521865.CrossRefGoogle Scholar
  12. 12.
    Bateman BT, Bykov K, Choudhry NK, Schneeweiss S, Gagne JJ, Polinski JM, Franklin JM, Doherty M, Fischer MA, Rassen JA. Type of stress ulcer prophylaxis and risk of nosocomial pneumonia in cardiac surgical patients: cohort study. BMJ (Clin Res ed). 2013;347:f5416.  https://doi.org/10.1136/bmj.f5416.CrossRefGoogle Scholar
  13. 13.
    Bruno JJ, Canada TW, Wakefield CD, Nates JL. Stress-related mucosal bleeding in critically ill oncology patients. J Oncol Pharm Pract. 2009;15(1):9–16.  https://doi.org/10.1177/1078155208094122.CrossRefPubMedGoogle Scholar
  14. 14.
    Buendgens L, Bruensing J, Matthes M, Duckers H, Luedde T, Trautwein C, Tacke F, Koch A. Administration of proton pump inhibitors in critically ill medical patients is associated with increased risk of developing Clostridium difficile-associated diarrhea. J Crit Care. 2014;29(4):696.e611–95.  https://doi.org/10.1016/j.jcrc.2014.03.002.CrossRefGoogle Scholar
  15. 15.
    Canada T. Does enteral nutrition provide stress ulcer prophylaxis in critically ill patients? Nutr Clin Pract. 1998;13(4):177.CrossRefGoogle Scholar
  16. 16.
    Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C, Farley MM, Dumyati GK, Wilson LE, Beldavs ZG, Dunn JR, Gould LH, MacCannell DR, Gerding DN, McDonald LC, Lessa FC. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med. 2013;173(14):1359–67.  https://doi.org/10.1001/jamainternmed.2013.7056.CrossRefPubMedGoogle Scholar
  17. 17.
    Conn HO, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med. 1994;236(6):619–32.CrossRefGoogle Scholar
  18. 18.
    Conrad SA, Gabrielli A, Margolis B, Quartin A, Hata JS, Frank WO, Bagin RG, Rock JA, Hepburn B, Laine L. Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med. 2005;33(4):760–5.CrossRefGoogle Scholar
  19. 19.
    Cook D, Guyatt G. Prophylaxis against upper gastrointestinal bleeding in hospitalized patients. N Engl J Med. 2018;378(26):2506–16.  https://doi.org/10.1056/NEJMra1605507.CrossRefPubMedGoogle Scholar
  20. 20.
    Cook D, Guyatt G, Marshall J, Leasa D, Fuller H, Hall R, Peters S, Rutledge F, Griffith L, McLellan A, Wood G, Kirby A. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med. 1998;338(12):791–7.  https://doi.org/10.1056/nejm199803193381203.CrossRefPubMedGoogle Scholar
  21. 21.
    Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med. 1999;27(12):2812–7.CrossRefGoogle Scholar
  22. 22.
    Cook DJ, Fuller HD, Guyatt GH, Marshall JC, Leasa D, Hall R, Winton TL, Rutledge F, Todd TJ, Roy P, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med. 1994;330(6):377–81.  https://doi.org/10.1056/nejm199402103300601.CrossRefPubMedGoogle Scholar
  23. 23.
    Cook DJ, Griffith LE, Walter SD, Guyatt GH, Meade MO, Heyland DK, Kirby A, Tryba M. The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care. 2001;5(6):368–75.CrossRefGoogle Scholar
  24. 24.
    Dayton MT, Kleckner SC, Brown DK. Peptic ulcer perforation associated with steroid use. Arch Surg (Chicago: 1960). 1987;122(3):376–80.CrossRefGoogle Scholar
  25. 25.
    El-Kersh K, Jalil B, McClave SA, Cavallazzi R, Guardiola J, Guilkey K, Persaud AK, Furmanek SP, Guinn BE, Wiemken TL, Alhariri BC, Kellie SP, Saad M. Enteral nutrition as stress ulcer prophylaxis in critically ill patients: A randomized controlled exploratory study. J Crit Care. 2018;43:108–13.  https://doi.org/10.1016/j.jcrc.2017.08.036.CrossRefPubMedGoogle Scholar
  26. 26.
    Ephgrave KS, Kleiman-Wexler RL, Adair CG. Enteral nutrients prevent stress ulceration and increase intragastric volume. Crit Care Med. 1990;18(6):621–4.CrossRefGoogle Scholar
  27. 27.
    Estruch R, Pedrol E, Castells A, Masanes F, Marrades RM, Urbano-Marquez A. Prophylaxis of gastrointestinal tract bleeding with magaldrate in patients admitted to a general hospital ward. Scand J Gastroenterol. 1991;26(8):819–26.CrossRefGoogle Scholar
  28. 28.
    Faisy C, Guerot E, Diehl JL, Iftimovici E, Fagon JY. Clinically significant gastrointestinal bleeding in critically ill patients with and without stress-ulcer prophylaxis. Intensive Care Med. 2003;29(8):1306–13.  https://doi.org/10.1007/s00134-003-1863-3.CrossRefPubMedGoogle Scholar
  29. 29.
    Guillamondegui OD, Gunter J, Oliver L., Bonadies JA, Coates JE, Kurek SJ, De Moya MA, Sing RF, Sori AJ. Practice management guidelines for stress ulcer prophylaxis. 2008. http://www.east.org/tpg/archive/html/stressulcer.html.
  30. 30.
    Huang HB, Jiang W, Wang CY, Qin HY, Du B. Stress ulcer prophylaxis in intensive care unit patients receiving enteral nutrition: a systematic review and meta-analysis. Crit Care (London). 2018;22(1):20.  https://doi.org/10.1186/s13054-017-1937-1.CrossRefGoogle Scholar
  31. 31.
    Kallam A, Singla A, Silberstein P. Proton pump induced thrombocytopenia: a case report and review of literature. Platelets. 2015;26(6):598–601.  https://doi.org/10.3109/09537104.2014.953045.CrossRefPubMedGoogle Scholar
  32. 32.
    Kantorova I, Svoboda P, Scheer P, Doubek J, Rehorkova D, Bosakova H, Ochmann J. Stress ulcer prophylaxis in critically ill patients: a randomized controlled trial. Hepato-Gastroenterology. 2004;51(57):757–61.PubMedGoogle Scholar
  33. 33.
    Kenneally C, Rosini JM, Skrupky LP, Doherty JA, Hollands JM, Martinez E, McKinzie WE, Murphy T, Smith JR, Micek ST, Kollef MH. Analysis of 30-day mortality for clostridium difficile-associated disease in the ICU setting. Chest. 2007;132(2):418–24.  https://doi.org/10.1378/chest.07-0202.CrossRefPubMedGoogle Scholar
  34. 34.
    Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, McArthur C, Cook D, Nielsen N, Pelosi P, Keus F, Guttormsen AB, Moller AD, Moller MH. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med. 2015a;41(5):833–45.  https://doi.org/10.1007/s00134-015-3725-1.CrossRefPubMedGoogle Scholar
  35. 35.
    Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, McArthur C, Cook D, Nielsen N, Pelosi P, Keus F, Guttormsen AB, Moller AD, Moller MH. Stress ulcer prophylaxis in the intensive care unit: an international survey of 97 units in 11 countries. Acta Anaesthesiol Scand. 2015b;59(5):576–85.  https://doi.org/10.1111/aas.12508.CrossRefPubMedGoogle Scholar
  36. 36.
    Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107(7):1011–9.  https://doi.org/10.1038/ajg.2012.108.CrossRefPubMedGoogle Scholar
  37. 37.
    Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007;102(9): 2047–56; quiz 2057.  https://doi.org/10.1111/j.1572-0241.2007.01275.x.CrossRefPubMedGoogle Scholar
  38. 38.
    Levy MJ, Seelig CB, Robinson NJ, Ranney JE. Comparison of omeprazole and ranitidine for stress ulcer prophylaxis. Dig Dis Sci. 1997;42(6):1255–9.CrossRefGoogle Scholar
  39. 39.
    MacLaren R, Reynolds PM, Allen RR. Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med. 2014;174(4):564–74.  https://doi.org/10.1001/jamainternmed.2013.14673.CrossRefPubMedGoogle Scholar
  40. 40.
    Madsen KR, Lorentzen K, Clausen N, Oberg E, Kirkegaard PR, Maymann-Holler N, Moller MH. Guideline for stress ulcer prophylaxis in the intensive care unit. Dan Med J. 2014;61(3):C4811.PubMedGoogle Scholar
  41. 41.
    McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):987–94.  https://doi.org/10.1093/cid/ciy149.CrossRefPubMedGoogle Scholar
  42. 42.
    Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open. 2014;4(5):e004587.  https://doi.org/10.1136/bmjopen-2013-004587.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Numico G, Fusco V, Franco P, Roila F. Proton Pump Inhibitors in cancer patients: How useful they are? A review of the most common indications for their use. Crit Rev Oncol Hematol. 2017;111:144–51.  https://doi.org/10.1016/j.critrevonc.2017.01.014.CrossRefPubMedGoogle Scholar
  44. 44.
    Pingleton SK, Hadzima SK. Enteral alimentation and gastrointestinal bleeding in mechanically ventilated patients. Crit Care Med. 1983;11(1):13–6.CrossRefGoogle Scholar
  45. 45.
    Piper DW, Fenton BH. pH stability and activity curves of pepsin with special reference to their clinical importance. Gut. 1965;6(5):506–8.CrossRefGoogle Scholar
  46. 46.
    Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;114(9):735–40.CrossRefGoogle Scholar
  47. 47.
    Priziola JL, Smythe MA, Dager WE. Drug-induced thrombocytopenia in critically ill patients. Crit Care Med. 2010;38(6 Suppl):S145–54.  https://doi.org/10.1097/CCM.0b013e3181de0b88.CrossRefPubMedGoogle Scholar
  48. 48.
    Puzanov I, Diab A, Abdallah K, Bingham CO 3rd, Brogdon C, Dadu R, Hamad L, Kim S, Lacouture ME, LeBoeuf NR, Lenihan D, Onofrei C, Shannon V, Sharma R, Silk AW, Skondra D, Suarez-Almazor ME, Wang Y, Wiley K, Kaufman HL, Ernstoff MS. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5(1):95.  https://doi.org/10.1186/s40425-017-0300-z.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Rathi NK, Tanner AR, Dinh A, Dong W, Feng L, Ensor J, Wallace SK, Haque SA, Rondon G, Price KJ, Popat U, Nates JL. Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage. Bone Marrow Transplant. 2015;50:420.CrossRefGoogle Scholar
  50. 50.
    Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45(3):486–552.  https://doi.org/10.1097/ccm.0000000000002255.CrossRefPubMedGoogle Scholar
  51. 51.
    Sartori S, Trevisani L, Nielsen I, Tassinari D, Abbasciano V. Misoprostol and omeprazole in the prevention of chemotherapy-induced acute gastroduodenal mucosal injury. A randomized, placebo-controlled pilot study. Cancer. 1996;78(7):1477–82.CrossRefGoogle Scholar
  52. 52.
    Sartori S, Trevisani L, Nielsen I, Tassinari D, Panzini I, Abbasciano V. Randomized trial of omeprazole or ranitidine versus placebo in the prevention of chemotherapy-induced gastroduodenal injury. J Clin Oncol Off J Am Soc Clin Oncol. 2000;18(3):463–7.  https://doi.org/10.1200/jco.2000.18.3.463.CrossRefGoogle Scholar
  53. 53.
    Selvanderan SP, Summers MJ, Finnis ME, Plummer MP, Ali Abdelhamid Y, Anderson MB, Chapman MJ, Rayner CK, Deane AM. Pantoprazole or Placebo for Stress Ulcer Prophylaxis (POP-UP): randomized double-blind exploratory study. Crit Care Med. 2016;44(10):1842–50.  https://doi.org/10.1097/ccm.0000000000001819.CrossRefPubMedGoogle Scholar
  54. 54.
    Solouki M, Marashian SM, Kouchak M, Mokhtari M, Nasiri E. Comparison between the preventive effects of ranitidineand omeprazole on upper gastrointestinal bleeding among ICU patients. Tanaffos. 2009;8(4): 37–42.Google Scholar
  55. 55.
    Soylu AR, Buyukasik Y, Cetiner D, Buyukasik NS, Koca E, Haznedaroglu IC, Ozcebe OI, Simsek H. Overt gastrointestinal bleeding in haematologic neoplasms. Dig Liver Dis. 2005;37(12):917–22.  https://doi.org/10.1016/j.dld.2005.07.017.CrossRefPubMedGoogle Scholar
  56. 56.
    Stollman N, Metz DC. Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care. 2005;20(1):35–45.CrossRefGoogle Scholar
  57. 57.
    Teva Pharmaceuticals Inc. (2017) Sucralfate [package insert]. North Wales, PA.Google Scholar
  58. 58.
    Tariq R, Singh S, Gupta A, Pardi DS, Khanna S. Association of gastric acid suppression with recurrent clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med. 2017;177(6):784–91.  https://doi.org/10.1001/jamainternmed.2017.0212.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Thorens J, Froehlich F, Schwizer W, Saraga E, Bille J, Gyr K, Duroux P, Nicolet M, Pignatelli B, Blum AL, Gonvers JJ, Fried M. Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study. Gut. 1996;39(1):54–9.CrossRefGoogle Scholar
  60. 60.
    Tseng CL, Chen YT, Huang CJ, Luo JC, Peng YL, Huang DF, Hou MC, Lin HC, Lee FY. Short-term use of glucocorticoids and risk of peptic ulcer bleeding: a nationwide population-based case-crossover study. Aliment Pharmacol Ther. 2015;42(5):599–606.  https://doi.org/10.1111/apt.13298.CrossRefPubMedGoogle Scholar
  61. 61.
    Wade EE, Rebuck JA, Healey MA, Rogers FB. H(2) antagonist-induced thrombocytopenia: is this a real phenomenon? Intensive Care Med. 2002;28(4): 459–65.  https://doi.org/10.1007/s00134-002-1233-6.CrossRefPubMedGoogle Scholar
  62. 62.
    Zandstra DF, Stoutenbeek CP. The virtual absence of stress-ulceration related bleeding in ICU patients receiving prolonged mechanical ventilation without any prophylaxis. A prospective cohort study. Intensive Care Med. 1994;20(5):335–40.CrossRefGoogle Scholar

Copyright information

© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020

Authors and Affiliations

  1. 1.Critical Care/Nutrition Support, Division of PharmacyThe University of Texas MD Anderson Cancer CenterHoustonUSA

Section editors and affiliations

  • Todd W. Canada
    • 1
  • Jeffrey J. Bruno
    • 2
  1. 1.Clinical Pharmacy Svcs, Pharmacy Clinical ProgramsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Clinical Pharmacy Specialist – Critical Care / Nutrition SupportThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations