Symptom Management in Gastrointestinal Cancers

  • Tugba Yavuzsen
  • Nazli Kazaz
  • Özgür Tanriverdi
  • Tulay Akman
  • Mellar P. Davis


Symptom management for gastrointestinal (GI) cancers depends on the type of cancer, the stage, the presence and kind of systemic symptoms such as anorexia, early satiety nausea, dysgeusia and smell changes, and comorbidities. Symptoms occur early, particularly in esophageal, gastric, and pancreatic cancers. Clinicians should assess a patient’s symptom burden at the time of diagnosis using validated questionnaires. Symptoms appear to cluster rather than appear in a random fashion. A group of symptoms may help in cancer diagnosis, management, and prognostication. Certain symptom clusters negatively affect quality of life and influence treatment compliance of patients as well as add to caregiver burden. Assessing evolving symptoms with follow-up and early palliative intervention can improve quality of life for a cancer patient.


Gastrointestinal cancer Symptom management Nutrition Chemotherapy-induced nausea and vomiting Mucositis Diarrhea Dysphagia Bowel obstruction Ascites Jaundice Hepatic encephalopathy Fatigue Hematology Anemia Thrombocytopenia Deep vein thrombosis Neuropsychiatric symptoms Ataxia Neuropathy Pain Skin problems 


  1. 1.
  2. 2.
    Hui D, Shamieh O, Paiva CE, Perex-Cruz PE, Kwon JH, Muckaden MA, et al. Minimal clinically important differences in the Edmonton Symptom Assessment Scale in cancer patients: a prospective, multicenter study. Cancer. 2015;121(17):3027–35.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kirkova J, Walsh D, Aktas A, Davis MP. Cancer symptom clusters: old concept but new data. Am J Hosp Palliat Care. 2010;27(4):282–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Aktas A. Cancer symptom clusters: current concepts and controversies. Curr Opin Support Palliat Care. 2013;7(1):38–44.CrossRefPubMedGoogle Scholar
  5. 5.
    Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733–42.CrossRefGoogle Scholar
  6. 6.
    Garla P, Waitzberg DL, Tesser A. Nutritional therapy in gastrointestinal cancers. Gastroenterol Clin N Am. 2018;47(1):231–42.CrossRefGoogle Scholar
  7. 7.
    Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F, et al. ESPEN guidelines on nutrition in cancer patients. Clin Nutr. 2017;36:11–48.CrossRefPubMedGoogle Scholar
  8. 8.
    Strasser F, Bruera ED. Up to date on anorexia and cachexia. Hematol Oncol Clin North Am. 2002;16(3):589–617.CrossRefPubMedGoogle Scholar
  9. 9.
    Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–95.CrossRefPubMedGoogle Scholar
  10. 10.
    Strasser F, Bruera E. Cancer anorexia/cachexia syndrome: epidemiology, pathogenesis, and assessment. In: Ripamonti C, Bruera E, editors. Gastrointestinal symptoms in advanced cancer patients. New York: Oxford University Press; 2002.Google Scholar
  11. 11.
    Aoyagi T, Terracina KP, Raza A, Matsubara H, Takabe K. Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol. 2015;7(4):17–29.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med. 1980;69(4):491–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Warren S. The immediate cause of death in cancer. Am J Med Sci. 1932;184:610–3.CrossRefGoogle Scholar
  14. 14.
    Davis MP, Dreicer R, Walsh D, Lagman R, LeGrand S. Appetite and cancer associated anorexia: a review. J Clin Oncol. 2004;22(8):1510–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Yavuzsen T, Walsh D, Davis MP, Kirkova J, Jin T, LeGrand S, et al. Components of the anorexia-cachexia syndrome: gastrointestinal symptom correlates of anorexia. Support Care Cancer. 2009;17(12):1531–41.CrossRefPubMedGoogle Scholar
  16. 16.
    Kirkova J, Davis MP, Walsh D, Tiernen E, O’leary N, LeGrand SB, et al. Cancer symptom assessment instruments: a systematic review. J Clin Oncol. 2006;24(9):1459–73.CrossRefPubMedGoogle Scholar
  17. 17.
    Davis MP, Yavuzsen T, Kirkova J, Walsh D, Karafa M, LeGrand S, et al. Validation of a simplified anorexia questionnaire. J Pain Symptom Manag. 2009;38(5):691–7.CrossRefGoogle Scholar
  18. 18.
    Andreyev HJ, Norman AR, Oates J, Cunnigham D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? Eur J Cancer. 1998;34(4):503–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Aapro M, Arends J, Bozzetti F, Fearon K, Grunberg SM, Herrstedt J, et al. Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force. Ann Oncol. 2014;25(8):1492–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Wallengren O, Lundholm K, Bosaeus I. Diagnostic criteria of cancer cachexia: relation to QOL, exercise capacity and survival in unselected palliative care patients. Support Care Cancer. 2013;21(6):1569–77.CrossRefPubMedGoogle Scholar
  21. 21.
    Trajkovic-Vidakovic M, de Graeff A, Voest EE, Teunissen SC. Symptoms tell it all: a systematic review of the value of symptom assessment to predict survival in advanced cancer patients. Crit Rev Oncol Hematol. 2012;84(1):130–48.CrossRefPubMedGoogle Scholar
  22. 22.
    Mei KL, Batsis JA, Mills JB, Holubar SD. Sarcopenia and sarcopenic obesity: do they predict inferior oncologic outcomes after gastrointestinal cancer surgery? Perioper Med (Lond). 2016;5:30.CrossRefGoogle Scholar
  23. 23.
    Anandavadivelan P, Brismar TB, Nilsson M, Johar AM, Martin L. Sarcopenic obesity: a probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients. Clin Nutr. 2016;35(3):724–30.CrossRefPubMedGoogle Scholar
  24. 24.
    Chow R, Bruera E, Chiu L, Chow S, Chiu N, Lam H, et al. Enteral and parenteral nutrition in cancer patients: a systematic review and meta-analysis. Ann Palliat Med. 2016;5(1):30–41.PubMedGoogle Scholar
  25. 25.
    Stephenson J, Davies A. An assessment of etiology-based guidelines for the management of nausea and vomiting in patients with advanced cancer. Support Care Cancer. 2006;14:348–53.CrossRefPubMedGoogle Scholar
  26. 26.
    Wickham R. Evolving treatment paradigms for chemotherapy-induced nausea and vomiting. Cancer Control. 2012;19(2 Suppl):3–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Darmani NA, Crim JL, Janoyan JJ, Abad J, Ramirez J. A re-evaluation of the neurotransmitter basis of chemotherapy-induced immediate and delayed vomiting: evidence from the least shrew. Brain Res. 2009;1248:40–58.CrossRefPubMedGoogle Scholar
  28. 28.
    Gordon P, Le Grand SB, Walsh D. Nausea and vomiting in advanced cancer. Eur J Pharmacol. 2014;722:187–91.CrossRefPubMedGoogle Scholar
  29. 29.
    Oosten AW, Oldenmenger WH, Mathijssen RH, van der Rijt CC. A systematic review of prospective studies reporting adverse events of commonly used opioids for cancer related pain: a call for the use of standardized outcome measures. J Pain. 2015;16(10):935–46.CrossRefPubMedGoogle Scholar
  30. 30.
    Donthireddy KR, Ailawadhi S, Nasser E, Schiff MD, Nwogu CE, Nava HR, et al. Malignant gastroparesis: pathogenesis and management of an under recognized disorder. J Support Oncol. 2007;5(8):355–63.PubMedGoogle Scholar
  31. 31.
    Davis MP, Walsh D, Lagman R, Yavuzsen T. Early satiety in cancer patients: a common and important but under recognized symptom. Support Care Cancer. 2006;14(7):693–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Warr DG. Chemotherapy and cancer related nausea and vomiting. Curr Oncol. 2008;15(Suppl 1):4–9.CrossRefGoogle Scholar
  33. 33.
    Aprile G, Rihawi K, De Carlo E, Sonis ST. Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer: a critical update. World J Gastroenterol. 2015;21(41):11793–803.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Poon M, Hwang J, Dennis K, DeAngelis C, Zhang L, Chung H, et al. A novel prospective descriptive analysis of nausea and vomiting among patients receiving gastrointestinal radiation therapy. Support Care Cancer. 2016;24(4):1545–61.CrossRefPubMedGoogle Scholar
  35. 35.
    Bouganim N, Dranitsaris G, Hopkins S, Vandermeer L, Godbout L, Dent S, et al. Prospective validation of risk prediction indexes for acute and delayed chemotherapy-induced nausea and vomiting. Curr Oncol. 2012;19(6):e414–21.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Sullivan JR, Leyden MJ, Bell R. Decreased cisplatin-induced nausea and vomiting with chronic alcohol ingestion. N Engl J Med. 1983;309(13):796.CrossRefPubMedGoogle Scholar
  37. 37.
    Tonato M, Roila F, Del Favero A. Methodology of antiemetic trials: a review. Ann Oncol. 1991;2(2):107–14.CrossRefPubMedGoogle Scholar
  38. 38.
    Roila F, Tonato M, Basurto C, Bella M, Passalacqua R, Morsia D, et al. Antiemetic activity of high doses of metoclopramide combined with methylprednisolone versus metoclopramide alone in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research. J Clin Oncol. 1987;5(1):141–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Kris MG, Urba SG, Schwartzberg LS. Clinical round table monograph. Treatment of chemotherapy-induced nausea and vomiting: a post-MASCC 2010 discussion. Clin Adv Hematol Oncol. 2011;9(1):supp1–15.Google Scholar
  40. 40.
    Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med. 2008;358(23):2482–94.CrossRefPubMedGoogle Scholar
  41. 41.
    Grunberg SM, Osoba D, Hesketh PJ, Gralla RJ, Borjeson S, Rapoport BL, et al. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity–an update. Support Care Cancer. 2005;13(2):80–4.CrossRefPubMedGoogle Scholar
  42. 42.
    Schwartzberg L. Chemotherapy-induced nausea and vomiting: state of the art in 2006. J Support Oncol. 2006;4(2 Suppl 1):3–8.PubMedGoogle Scholar
  43. 43.
    Hesketh PJ, Sanz-Altamira P, Bushey J, Hesketh AM. Prospective evaluation of the incidence of delayed nausea and vomiting in patients with colorectal cancer receiving oxaliplatin-based chemotherapy. Support Care Cancer. 2012;20(5):1043–7.CrossRefPubMedGoogle Scholar
  44. 44.
    Schwartzberg L. Addressing the value of novel therapies in chemotherapy-induced nausea and vomiting. Expert Rev Pharmacoecon Outcomes Res. 2014;14(6):825–34.CrossRefPubMedGoogle Scholar
  45. 45.
    Sekine I, Segawa Y, Kubota K, Saeki T. Risk factors of chemotherapy-induced nausea and vomiting: index for personalized antiemetic prophylaxis. Cancer Sci. 2013;104(6):711–7.CrossRefPubMedGoogle Scholar
  46. 46.
    Roscoe JA, Morrow GR, Hickok JT, Stern RM. Nausea and vomiting remain a significant clinical problem: trends over time in controlling chemotherapy-induced nausea and vomiting in 1413 patients treated in community clinical practices. J Pain Symptom Manag. 2000;20(2):113–21.CrossRefGoogle Scholar
  47. 47.
    Hesketh PJ, Bohlke K, Kris MG. Antiemetics: American Society of Clinical Oncology clinical practice guideline update summary. J Oncol Pract. 2017;13(12):825–30.CrossRefPubMedGoogle Scholar
  48. 48.
    Morrow GR, Roscoe JA, Kirshner JJ, Hynes HE, Rosenbluth RJ. Anticipatory nausea and vomiting in the era of 5-HT3 antiemetics. Support Care Cancer. 1998;6(3):244–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Morrow GR, Roscoe JA, Hickok JT. Nausea and vomiting. In: Holland JC, Breitbart W, Jacobsen PB, et al., editors. Psycho-oncology. New York: Oxford University Press; 1998. p. 476–84.Google Scholar
  50. 50.
    Malik IA, Khan WA, Qazilbash M, Ata E, Butt A, Khan MA. Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial. Am J Clin Oncol. 1995;18(2):170–5.CrossRefPubMedGoogle Scholar
  51. 51.
    Aapro MS, Molassiotis A, Olver I. Anticipatory nausea and vomiting. Support Care Cancer. 1995;13(2):117–21.CrossRefGoogle Scholar
  52. 52.
    Ravazi D, Delvaux N, Farvacques CJ, De Brier F, Van Heer C, Kaufman L, et al. Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy: a double- blind, placebo-controlled study assessing the usefulness of a alprazolam. J Clin Oncol. 1993;11(7):1384–90.CrossRefGoogle Scholar
  53. 53.
    Carey MP, Burish TG. Etiology and treatment of the psychological side effects associated with cancer chemotherapy: a critical review and discussion. Psychol Bull. 1988;104(3):307–25.CrossRefPubMedGoogle Scholar
  54. 54.
    Lyles JN, Burish TG, Krozely MG, Oldham RK. Efficacy of relaxation training and guided imagery in reducing the aversiveness of cancer chemotherapy. J Consult Clin Psychol. 1982;50(4):509–24.CrossRefPubMedGoogle Scholar
  55. 55.
    Redd WH, Andresen GV, Minagawa RY. Hypnotic control of anticipatory emesis in patients receiving cancer chemotherapy. J Consult Clin Psychol. 1982;50(1):14–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Morrow GR, Morrell C. Behavioral treatment for the anticipatory nausea and vomiting induced by cancer chemotherapy. N Engl J Med. 1982;307(24):1476–80.CrossRefPubMedGoogle Scholar
  57. 57.
    Hesketh PJ, Bohlke K, Lyman GH, Basch E, Chesney M, Clark-Snow RA, et al. Antiemetics: American Society of Clinical Oncology focused guideline update. J Clin Oncol. 2016;34(4):381–6.CrossRefPubMedGoogle Scholar
  58. 58.
    Tageja N, Groninger H. Chemotherapy-induced nausea and vomiting: an overview and comparison of three consensus guidelines. Postgrad Med J. 2016;92(1083):33–40.CrossRefGoogle Scholar
  59. 59.
    Lotfi-Jam K, Carey M, Jefford M, Schofield P, Charleson C, Aranda S. Nonpharmacologic strategies for managing common chemotherapy adverse effects: a systematic review. J Clin Oncol. 2008;26(34):5618–29.CrossRefPubMedGoogle Scholar
  60. 60.
    Miroddi M, Sterrantino C, Simonelli I, Ciminata G, Philips RS, Calapai G. Risk of grade 3-4 diarrhea and mucositis in colorectal cancer patients receiving anti-EGFR monoclonal antibodies regimens: a meta-analysis of 18 randomized controlled clinical trials. Crit Rev Oncol Hematol. 2015;96(2):355–61.CrossRefPubMedGoogle Scholar
  61. 61.
    Lee CS, Ryan EJ, Doherty GA. Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: the role of inflammation. World J Gastroenterol. 2014;20(14):3751–61.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Jones JA, Avritscher EB, Cooksley CD, Michelet M, Bekele BN, Elting LS. Epidemiology of treatment-associated mucosal injury after treatment with newer regimens for lymphoma, breast, lung, or colorectal cancer. Support Care Cancer. 2006;14(6):505–15.CrossRefPubMedGoogle Scholar
  63. 63.
    Logan RM, Gibson RJ, Bowen JM, Stringer AM, Sonis ST, Keefe DM. Characterization of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis. Cancer Chemother Pharmacol. 2008;62(1):33–41.CrossRefPubMedGoogle Scholar
  64. 64.
    Sonic ST, Elting RS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(9 Suppl):1995–2025.Google Scholar
  65. 65.
    Andre T, Colin P, Louvet C, Gamelin E, Bouche O, Achille E, et al. Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial. J Clin Oncol. 2003;21(15):2896–903.CrossRefPubMedGoogle Scholar
  66. 66.
    Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005;352(26):2696–704.CrossRefPubMedGoogle Scholar
  67. 67.
    Yuan A, Kurtz SL, Barysauskas CM, Pilotte AP, Wagner AJ, Treister NS. Oral adverse events in cancer patients treated with VEGFR-directed multitargeted tyrosine kinase inhibitors. Oral Oncol. 2015;51(11):1026–33.CrossRefPubMedGoogle Scholar
  68. 68.
    Grothey A, Georga S, van Cutsem E, Blsy JY, Sobrero A, Demetri GD. Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care. Oncologist. 2014;19(6):669–80.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, et al., The Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120(10):1453–61.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Feldman JM. Carcinoid tumors and syndrome. Semin Oncol. 1987;14(3):237–46.PubMedGoogle Scholar
  71. 71.
    Narayanan S, Kunz PL. Role of somatostatin analogues in the treatment of neuroendocrine tumors. Hematol Oncol Clin North Am. 2016;30(1):163–77.CrossRefPubMedGoogle Scholar
  72. 72.
    Dillon JS, Chandrasekharan C. Telotristat ethyl: a novel agent for the therapy of carcinoid syndrome diarrhea. Future Oncol. 2018;14(12):1155–64.CrossRefPubMedGoogle Scholar
  73. 73.
    Pusceddu S, De Braud F, Festinese F, Bregant C, Lorenzoni A, Maccauro M, et al. Evolution in the treatment of gastroenteropancreatic-neuroendocrine neoplasm, focus on systemic therapeutic options: a systematic review. Future Oncol. 2015;11(13):1947–59.CrossRefPubMedGoogle Scholar
  74. 74.
    van Rossum PSN, Mohammad NH, Vleggaar FP, van Hillegersberg R. Treatment for unresectable or metastatic oesophageal cancer: current evidence and trends. Nat Rev Gastroenterol Hepatol. 2018;15(4):235–49.CrossRefPubMedGoogle Scholar
  75. 75.
    Doosti-Irani A, Mansournia MA, Rahimi-Foroushani A, Haddad P, Holakouie-Naieni K. Complications of stent placement in patients with esophageal cancer: a systematic and network analysis. PLoS One. 2017;12(10):e0184784.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Miller G, Boman J, Shrier I, Gordon PH. Small-bowel obstruction secondary to malignant disease: an 11-year audit. Can J Surg. 2000;43(5):353–8.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Baines M, Oliver DJ, Carter RL. Medical management of intestinal obstruction in patients with advanced malignant disease. A clinical and pathological study. Lancet. 1985;2(8462):990–3.CrossRefPubMedGoogle Scholar
  78. 78.
    Librach SL, Horvath AN, Langlois EA. Malignant bowel obstruction. In: Palliative Medicine – a case based manual. 2nd ed. New York: Oxford University Press Inc.; 2005. p. 213–7.Google Scholar
  79. 79.
    Anthony T, Baron T, Mercadante S, Green S, Chi D, Cunningham J, et al. Report of the clinical protocol committee: development of randomized trials for malignant bowel obstruction. J Pain Symptom Manag. 2007;34(Suppl 1):49–59.CrossRefGoogle Scholar
  80. 80.
    Tuca A, Guell E, Martinez-Losada E, Codorniu N. Malignant bowel obstruction in advanced cancer patients: epidemiology, management, and factors influencing spontaneous resolution. Cancer Manag Res. 2012;4:159–69.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Tuca A, Codorniu N, Garzón, Serrano G. Malignant bowel obstruction due to advanced cancer in palliative care: observational and descriptive study. 5th Research Forum of European Association for Palliative Care; May 2008; Trodheim, Norway. Poster: 462.Google Scholar
  82. 82.
    Laval G, Marcelin-Benazech B, Guirimand F. Recommendations for bowel obstruction with peritoneal carcinomatosis. J Pain Symptom Manag. 2014;48(1):75–91.CrossRefGoogle Scholar
  83. 83.
    Francescutti V, Miller A, Satchidanand Y. Management of bowel obstruction in patients with stage IV cancer: predictors of outcome after surgery. Ann Surg Oncol. 2013;20(3):707–14.CrossRefPubMedGoogle Scholar
  84. 84.
    Ripamonti C, Twycross R, Baines M, Bozzetti F, Capri S, De Conno F, et al. Clinical-practice recommendations for the management of bowel obstruction in patients with end-stage cancer. Support Care Cancer. 2001;9(4):223–33.CrossRefPubMedGoogle Scholar
  85. 85.
    Smith EM, Jayson GC. The current and future management of malignant ascites. Clin Oncol (R Coll Radiol). 2003;15(2):59–72. (review).CrossRefPubMedGoogle Scholar
  86. 86.
    Nagy JA, Herzberg KT, Dvorak JM, Dvorak HM. Pathogenesis ascites formation: initiating events that lead to fluid accumulation. Cancer Res. 1993;53:2631–43.PubMedGoogle Scholar
  87. 87.
    Lee CW, Bociek G, Faught W. A survey of practice in management of malignant ascites. J Pain Symptom Manag. 1998;16(2):96–101.CrossRefGoogle Scholar
  88. 88.
    Fleming ND, Alvarez-Secord A, Von Grueningen V, Miller MJ, Abernetjy AP. Indwelling catheters for the management of refractory malignant ascites: a systematic literature overview and retrospective chart review. J Pain Symptom Manag. 2009;38(3):341–9.CrossRefGoogle Scholar
  89. 89.
    Randle RW, Sweet KR, Swords DS, Shen P, Stewart JH, Levine EA, et al. Efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in the management of malignant ascites. Ann Surg Oncol. 2014;21(5):1474–9.CrossRefPubMedGoogle Scholar
  90. 90.
    Cavazzoni E, Bugiantella W, Graziosi L, Franceschini MS, Donini A. Malignant ascites: pathophysiology and treatment. Int J Clin Oncol. 2013;18(1):1–9.CrossRefPubMedGoogle Scholar
  91. 91.
    Boulay BR, Parepally M. Managing malignant biliary obstruction in pancreas cancer: choosing the appropriate strategy. World J Gastroenterol. 2014;20(28):9345–53.PubMedPubMedCentralGoogle Scholar
  92. 92.
    Ho CS, Warkentin AE. Evidence based decompression in malignant biliary obstruction. Korean J Radiol. 2012;13(S1):S56–61.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Franc M, Michalski B, Kuczerawy I, Szuta J, Skrzypulec-Plinta V. Cancer related fatigue syndrome in neoplastic diseases. Prz Menopauzalny. 2014;13(6):352–5.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Huang X, Zhang Q, Kang X, Song Y, Zhao W. Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study. BMC Cancer. 2010;10:453.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Pettersson G, Berterö C, Unosson M, Börjeson S. Symptom prevalence, frequency, severity, and distress during chemotherapy for patients with colorectal cancer. Support Care Cancer. 2014;22(5):1171–9.CrossRefPubMedGoogle Scholar
  96. 96.
    Li SX, Liu BB, Lu JH. Longitudinal study of cancer-related fatigue in patients with colorectal cancer. Asian Pac J Cancer Prev. 2014;15(7):3029–33.CrossRefPubMedGoogle Scholar
  97. 97.
    Arndt V, Merx H, Stegmaier C, Ziegler H, Brenner H. Restrictions in QOL in colorectal cancer patients over three years after diagnosis: a population based study. Eur J Cancer. 2006;42(12):1848–57.CrossRefPubMedGoogle Scholar
  98. 98.
    O’Gorman C, Denieffe S, Gooney M. Literature review: preoperative radiotherapy and rectal cancer impact on acute symptom presentation and QOL. J Clin Nurs. 2013;23(3–4):333–51.PubMedGoogle Scholar
  99. 99.
    Stauder MC, Romero BK, Atherton DG, Deschamps C, Jatoi A, Sloan JA, et al. Overall survival and self-reported fatigue in patients with esophageal cancer. Support Care Cancer. 2013;21(2):511–9.CrossRefPubMedGoogle Scholar
  100. 100.
    Kitano T, Tada H, Nishimura T, Teramukai S, Kanai M, Nishimura T, et al. Prevalence and incidence of anemia in Japanese cancer patients receiving outpatient chemotherapy. Int J Hematol. 2007;86(1):37–41.CrossRefPubMedGoogle Scholar
  101. 101.
    Vardy J, Dhillon HM, Pond GR, Rourke SB, Xu W, Dodd A, et al. Cognitive function and fatigue after diagnosis of colorectal cancer. Ann Oncol. 2014;25(12):2404–12.CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Scott JA, Lasch KE, Barsevick AM, Piault-Louis E. Patient’s experiences with cancer-related fatigue: a review and synthesis of qualitative research. Oncol Nurs Forum. 2011;38(3):E191–203.CrossRefPubMedGoogle Scholar
  103. 103.
    Lin J-M, Brimmer DJ, Maloney EM, Nyarko E, Belue R, Reeves WC. Further validation of the Multidimensional Fatigue Inventory in a US adult population sample. Popul Health Metrics. 2009;7:18.CrossRefGoogle Scholar
  104. 104.
    Brola W, Ziomek M, Czernicki J. Fatigue syndrome chronic neurological disorder. Neurol Neurochir Pol. 2007;41(4):340–9.PubMedGoogle Scholar
  105. 105.
    Minton O, Stone PC. The use of proteomics as a research methodology for studying cancer-related fatigue: a review. Palliat Med. 2010;24(3):310–6.CrossRefPubMedGoogle Scholar
  106. 106.
    Popiela T, Lucchi R, Giongo F. Methylprednisolone as palliative therapy for female terminal cancer patients. The Methylprednisolone Female Preterminal Cancer Study Group. Eur J Cancer Clin Oncol. 1989;25(12):1823–9.CrossRefPubMedGoogle Scholar
  107. 107.
    De Conno F, Martini C, Zecca E, Balzarini A, Venturino P, Groff L, et al. Megestrol acetate for anorexia in patients with far-advanced cancer: a double-blind controlled clinical trial. Eur J Cancer. 1998;34(11):1705–9.CrossRefPubMedGoogle Scholar
  108. 108.
    Lower EE, Fleishman S, Cooper A, Zeldis J, Faleck H, Yu Z, et al. Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. J Pain Symptom Manag. 2009;38(5):650–62.CrossRefGoogle Scholar
  109. 109.
    Bruera E, Yennurajalingam S, Palmer JL, Perez-Cruz PE, Frisbee-Hume S, Allo J, et al. Methylphenidate and/or a nursing telephone intervention for fatigue in patients with advanced cancer: a randomized, placebo-controlled, phase II trial. J Clin Oncol. 2013;31(19):2421–7.CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Spathis A, Dhillan R, Booden D, Forbes K, Vrotsou K, Fife K. Modafinil for the treatment of fatigue in lung cancer: a pilot study. Palliat Med. 2009;23:325–31.CrossRefPubMedGoogle Scholar
  111. 111.
    Barton DL, Liu H, Dakhil SR, Linquist B, Sloan JA, Nichols CR, et al. Wisconsin ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. J Natl Cancer Inst. 2013;105(16):1230–8.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Jensen W, Baumann FT, Stein A, Bloch W, Bokemeyer C, de Wit M, et al. Exercise training in patients with advanced gastrointestinal cancer undergoing palliative chemotherapy: a pilot study. Support Care Cancer. 2014;22(7):1797–806.PubMedGoogle Scholar
  113. 113.
    Pachman DR, Price KA, Carey EC. Nonpharmacologic approach to fatigue in patients with cancer. Cancer. 2014;20(5):313–8.CrossRefGoogle Scholar
  114. 114.
    Maguire D, O’Sullivan GC, Collins JK, Morgan J, Shanahan F. Bone marrow micro-metastases and gastrointestinal cancer detection and significance. Am J Gastroenterol. 2000;95:1644–51.CrossRefPubMedGoogle Scholar
  115. 115.
    Wang Y, Probin V, Zhou D. Cancer therapy-induced residual bone marrow injury-mechanisms of induction and implication for therapy. Curr Cancer Ther Rev. 2006;2(3):271–9.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Varma A, Spier BJ, Pfau PR, Safdar N. A case of newly diagnosed metastatic pancreatic cancer presenting with associated immune thrombocytopenic purpura. Wis Med J. 2009;108(9):459–61.Google Scholar
  117. 117.
    Zhu A, Kaneshiro M, Kaunitz JD. Evaluation and treatment of iron deficiency anemia: a gastroenterological perspective. Dig Dis Sci. 2010;55(3):548–59.CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Yachimski PS, Friedman LS. Gastrointestinal bleeding in the elderly. Nat Clin Pract Gastroenterol Hepatol. 2008;5(2):80–93.CrossRefPubMedGoogle Scholar
  119. 119.
    Pelesof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clin Proc. 2010;85(9):838–54.CrossRefGoogle Scholar
  120. 120.
    Reese JA, Bougie DW, Curtis BR, Terrell DR, Vesely SK, Aster RH, et al. Drug-induced thrombotic microangiopathy: experience of the Oklahoma Registry and the Blood Center of Wisconsin. Am J Hematol. 2015;90(5):406–10.CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    Niu J, Mims MP. Oxaliplatin-induced thrombotic thrombocytopenic purpura: case report and literature review. J Clin Oncol. 2012;30(31):1705.CrossRefGoogle Scholar
  122. 122.
    Mimica M, Tomic M, Babic E, Karin M, Bevanda M, Alfirevic D, et al. Gastric cancer with bone marrow invasion presenting as severe thrombocytopenia. Turk J Gastroenterol. 2014;25(Suppl 1):229–30.PubMedGoogle Scholar
  123. 123.
    Arslan D, Uysal M, Tatli AM, Gunduz S, Sezgin-Goksu S, Bassorgun CI, Coskun HS, Bozcuk H, Savas B. Her-2 positive gastric cancer presented with thrombocytopenia and skin involvement: a case report. Case Rep Oncol Med. 2014;2014:194636.PubMedPubMedCentralGoogle Scholar
  124. 124.
    Yazdi MF, Hashemian Z, Nazmieh H, Ghadimi H. A report of three cases with thrombotic thrombocytopenic purpura (TTP) secondary to an occult gastric adenocarcinoma. Pak J Med Sci. 2009;25(4):689–92.Google Scholar
  125. 125.
    Lechner K, Obermeier HL. Cancer-related microangiopathic hemolytic anemia: clinical and laboratory features in 168 reported cases. Medicine. 2012;91(4):1–11.CrossRefGoogle Scholar
  126. 126.
    Khorana AA. Cancer-associated thrombosis: updates and controversies. Hematology Am Soc Hematol Educ Program. 2012;2012:626–30.PubMedGoogle Scholar
  127. 127.
    Khorana AA, Fine RL. Pancreatic cancer and thromboembolic disease. Lancet Oncol. 2004;5(11):655–63.CrossRefPubMedGoogle Scholar
  128. 128.
    Sheth RA, Niekamp A, Quencer KB, Shamoun F, Knuttinen MG, Naidu S, et al. Thrombosis in cancer patients: etiology, incidence, and management. Cardiovasc Diagn Ther. 2017;7(Suppl):S178–85.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Chai-Adisaksopha C, Iorio A, Crowther MA, de Miguel J, Salgado E, Zdraveska M, et al. Vitamin K antagonists after 6 months of low-molecular-weight heparin in cancer patients with venous thromboembolism. Am J Med. 2017;131(4):430–7. pii: S0002-9343(17)31277-9.CrossRefPubMedGoogle Scholar
  130. 130.
    Elalamy I, Mahe I, Ageno W, Meyer G. Long term treatment of cancer associated thrombosis: the choice of the optimal anticoagulant. J Thromb Haemost. 2017;15(5):848–57.CrossRefPubMedGoogle Scholar
  131. 131.
    Melosky B. Supportive care treatments for toxicities of anti-egfr and other targeted agents. Curr Oncol. 2012;19(Suppl 1):S59–63.PubMedPubMedCentralGoogle Scholar
  132. 132.
    De Loughery TG, Beer TM. Bevacizumab and thrombosis: some answers but questions remain. Cancer. 2015;121(7):975–7.CrossRefGoogle Scholar
  133. 133.
    Newton HB. Neurological complications of systemic cancer. Am Fam Physician. 1999;59(4):878–86.PubMedGoogle Scholar
  134. 134.
    Giglio P, Gilbert MR. Neurological complications of cancer and treatment. Curr Oncol Rep. 2010;12(1):50–9.CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Sio TT, Paredes M, Uzair C. Neurological manifestation of colonic adenocarcinoma. Rare Tumors. 2012;4(2):e32.CrossRefPubMedPubMedCentralGoogle Scholar
  136. 136.
    Bano N, Najam R, Mateen A. Neurological adverse effects in patients of advanced colorectal carcinoma treated with different schedules of FOLFOX. Chemother Res Pract. 2013;2013:379870.PubMedPubMedCentralGoogle Scholar
  137. 137.
    Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32(18):1941–67.CrossRefPubMedGoogle Scholar
  138. 138.
    Klicovac T, Djurdjevic A. Psychological aspects of the cancer patients’ education: thoughts, feelings, behavior and body reaction of patients faced with diagnosis of cancer. J BUON. 2010;15(1):153–6.Google Scholar
  139. 139.
    Deckx L, van Abbema DL, van den Akker M, van den Broeke C, van Driel M, Bulens P, et al. A cohort study on the evolution of psychosocial problems in older patients with breast or colorectal cancer: comparison with younger cancer patients and older primary care patients without cancer. BMC Geriatr. 2015;15:79.CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Vardy JL, Dhillon HM, Pond GR, Rourke SB, Bekele T, Renton C, et al. Cognitive function in patients with colorectal cancer who do and do not receive chemotherapy: a prospective, longitudinal, controlled study. J Clin Oncol. 2015;33(34):4085–92.CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Detrich J, Prust M, Kaiser J. Chemotherapy, cognitive impairment and hippocampal toxicity. Neuroscience. 2015;309:224–32.CrossRefGoogle Scholar
  142. 142.
    Centeno C, Sanz A, Bruera E. Delirium in advanced cancer patients. Palliat Med. 2004;18(3):184–94.CrossRefGoogle Scholar
  143. 143.
    Merskey H, Bugduk N. Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms. 2nd ed. Seattle: IASP Press; 1994.Google Scholar
  144. 144.
    Van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, Van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007;18(9):1437–49.Google Scholar
  145. 145.
    Homsi J, Walsh D, Rivera N, Rybicki LA, Nelson KA, LeGrand SB, et al. Symptom evaluation in palliative medicine: patient report vs systematic assessment. Support Care Cancer. 2006;14(5):444–53.CrossRefPubMedGoogle Scholar
  146. 146.
    Breivik H, Cherny N, Collett B, de Conno F, Filbet M, Foubert AJ, et al. Cancer-related pain: a pan-European survey of prevalence, treatment, and patient attitudes. Ann Oncol. 2009;20(8):1420–33.CrossRefPubMedGoogle Scholar
  147. 147.
    Pathophysiology of cancer pain and opioid tolerance. In: The British Pain Society’s cancer pain management. 2010. Accessed 12 June 2018.
  148. 148.
    Grond S, Zech D, Difenbach C, Radburgh L, Lehmann KA. Assessment of the cancer pain: a prospective evaluation in 2266 cancer patients referred to a pain service. Pain. 1996;64(1):107–14.CrossRefPubMedGoogle Scholar
  149. 149.
    Walsh D. Pharmacological management of cancer pain. Semin Oncol. 2000;27(1):45–63.PubMedGoogle Scholar
  150. 150.
    Vielhaber A, Portenoy RK. Advances in cancer pain management. Hematol Oncol Clin North Am. 2002;16(3):527–41.CrossRefPubMedGoogle Scholar
  151. 151.
    Stacey B. Management of peripheral neuropathic pain. Am J Phys Med Rehabil. 2005;84(3):S4–S16.PubMedGoogle Scholar
  152. 152.
    Bennett MI, Rayment C, Hjermstad M, Aass N, Caraceni A, Kaasa S. Prevalence and aetiology of neuropathic pain in cancer patients: a systematic review. Pain. 2012;153(2):359–65.CrossRefPubMedGoogle Scholar
  153. 153.
    de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, et al. Leucovorin and fluorouracil with and without, oxaliplatin as first-line treatment in advanced cancer. J Clin Oncol. 2000;18(6):2938–47.CrossRefPubMedGoogle Scholar
  154. 154.
    Andre T, Boni C, Mounedji-Boudiat L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350(23):2343–51.CrossRefPubMedGoogle Scholar
  155. 155.
    Briani C, Argyriou A, Izquierd C, Velasco R, Campagnolo M, Alberti P, et al. Long-term course of oxaliplatin-induced polyneuropathy: a prospective 2-year follow-up study. J Peripher Nerv Syst. 2014;19(4):299–306.CrossRefPubMedGoogle Scholar
  156. 156.
    Mercandante S, Klepstad P, Kurita GP, Sjogren P, Giarratano A, European Palliative Care Research Collaborative Group (EPCRC). Sympathetic blocks for visceral cancer pain management: a systematic review and EAPC recommendations. Crit Rev Oncol Hematol. 2015;96(3):577–83.CrossRefGoogle Scholar
  157. 157.
    Ripamonti C, De Conno F, Ventafridda V, Rossi B, Baines MJ. Management of bowel obstruction in advanced and terminal cancer patients. Ann Oncol. 1993;4(1):15–21.CrossRefPubMedGoogle Scholar
  158. 158.
    Alexandrescu DT, Wiernik PH, Dutcher JP. Chapter 90. Chemotherapy toxicities and complications. In: Young NS, Gerson SL, High KA, editors. Clinical hematology. Philadelphia: Mosby Elsevier; 2006. p. 1144–54.Google Scholar
  159. 159.
    Kurkjian DC, Ozer H. Management of adverse effects of treatment. In: Devita VT, Lawrence TS, Rosenberg SA, Weinberg RA, editors. DeVita, Hellman and Rosenberg’s cancer: principles & practice of oncology. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2008. p. 2617–38.Google Scholar
  160. 160.
    Minisini AM, Tosti A, Sobrero AF, Mansutti M, Piraccini BM, Sacco C, et al. Taxane induced nail changes: incidence, clinical presentation and outcome. Ann Oncol. 2003;14(2):333–7.CrossRefPubMedGoogle Scholar
  161. 161.
    Robert C, Sibaud V, Mateus C, Verschoore M, Charles C, Lanoy E, et al. Nail toxicities induced by systemic anticancer treatments. Lancet Oncol. 2015;16(4):e181–e9.CrossRefPubMedGoogle Scholar
  162. 162.
    Lipworth AD, Robert C, Zhu A. Hand-foot syndrome (Hand-foot skin reaction, palmar-plantar erythrodysesthesia): focus on sorafenib and sunitinib. Oncology. 2009;77(5):257–71.CrossRefPubMedGoogle Scholar
  163. 163.
    Fabian CJ, Molina R, Slavik M, Dahlberg S, Giri S, Stephens R. Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion. Investig New Drugs. 1990;8(1):57–63.CrossRefGoogle Scholar
  164. 164.
    Kang YK, Lee SS, Yoon DH, Lee SY, Chun YJ, Kim MS, et al. Pyridoxine is not effective to prevent hand-foot syndrome associated with capecitabine therapy: results of a randomized, double blind, placebo-controlled study. J Clin Oncol. 2010;28(24):3824–9.CrossRefPubMedGoogle Scholar
  165. 165.
    Curran CF, Luce JK. Fluorouracil and palmar-plantar erythrodysesthesia. Ann Intern Med. 1989;111(10):858.CrossRefPubMedGoogle Scholar
  166. 166.
    Comandone A, Bretti S, La Grotta G, Manzoni S, Bonardi G, Berardo R, et al. Palmar-plantar erythrodysesthesia syndrome associated with 5-fluorouracil treatment. Anticancer Res. 1993;13(5c):1781–3.PubMedGoogle Scholar
  167. 167.
    Busam KJ, Capodieci P, Motzer R, Kiehn T, Phelan D, Halpern AC. Cutaneous side-effects in cancer patients treated with the ant epidermal growth factor receptor antibody C225. Br J Dermatol. 2001;144(6):1169–76.CrossRefPubMedGoogle Scholar
  168. 168.
    Lacouture ME, Melosky BL. Cutaneous reactions to anticancer agents targeting the epidermal growth factor receptor: dermatology–oncology perspective. Skin Therapy Lett. 2007;12(6):1–5.PubMedGoogle Scholar
  169. 169.
    Fox LP. Pathology and management of dermatologic toxicities associated with anti-EGFR therapy. Oncology (Williston Park). 2006;20(5 Suppl 2):26–34.Google Scholar
  170. 170.
    Jatoi A, Rowland K, Sloan JA, Gross HM, Fishkin PA, Kahanic SP, et al. Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes: results of a placebo-controlled trial from the North Central Cancer Treatment Group (N03CB). Cancer. 2008;113(4):847–53.CrossRefPubMedPubMedCentralGoogle Scholar
  171. 171.
    Scope A, Agero AL, Dusza SW, Myskowski PL, Lieb JA, Saltz L, et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol. 2007;25(34):5390–6.CrossRefPubMedGoogle Scholar
  172. 172.
    Scope A, Lieb J, Dusza S, Phelan DL, Myskowski PL, Saltz L, et al. A prospective randomized trial of topical pimecrolimus for cetuximab-associated acne-like eruption. J Am Acad Dermatol. 2009;61(4):614–20.CrossRefPubMedGoogle Scholar
  173. 173.
    Pérez-Soler R, Delord JP, Halpern A, Kelly K, Krueger J, Sureda BM, et al. HER1/EGFR inhibitor–associated rash: future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum. Oncologist. 2005;10(5):345–56.CrossRefPubMedGoogle Scholar
  174. 174.
    Melosky B, Burkes R, Rayson D, Alcindor T, Shear N, Lacouture M, et al. Management of skin rash during EGFR-targeted monoclonal antibody treatment for gastrointestinal malignancies: Canadian recommendations. Curr Oncol. 2009;16(1):16–26.CrossRefPubMedPubMedCentralGoogle Scholar
  175. 175.
    Burris HA, Hurtig J. Radiation recall with anticancer agents. Oncologist. 2010;15(11):1227–37.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Tugba Yavuzsen
    • 1
  • Nazli Kazaz
    • 2
  • Özgür Tanriverdi
    • 3
  • Tulay Akman
    • 4
  • Mellar P. Davis
    • 5
  1. 1.Department of Internal Medicine, Division of Medical OncologyDokuz Eylul University Faculty of MedicineBalcova, IzmirTurkey
  2. 2.Department of Medical OncologyKaradeniz Technical University, Kanuni Training and Education HospitalTrabzonTurkey
  3. 3.Department of Medical OncologyMugla Sitki Kocman University Faculty of MedicineMenteşeTurkey
  4. 4.Department of Medical OncologyTepecik Education and Research HospitalIzmirTurkey
  5. 5.Lerner School of Medicine, Case Western Reserve University, Palliative Care Department, Geisinger Medical CenterDanvilleUSA

Personalised recommendations