Care of the Oncology Patient in the PICU

  • Robert J. Greiner
  • Stacey Peterson-Carmichael
  • Jennifer A. Rothman
  • Kenneth W. Gow
  • Robert F. TamburroJr.Email author
  • Raymond Barfield


There are numerous malignant conditions that place the pediatric patient at great risk requiring the need of critical care services. Therefore, it is essential that the pediatric critical care provider possess a sound understanding of these conditions such that they may be anticipated, recognized and treated effectively. Of these conditions, perhaps none requires the prompt, well conceived care of a pediatric intensivist as much as a malignant mediastinal mass. A definitive diagnosis must be established balancing the likelihood of a definitive result with the risk of the diagnostic procedure and the associated sedation. A clear understanding of the findings that suggest a patient is at high risk for airway compromise is essential. Hyperleukocytosis is another malignant condition associated with significant morbidity and mortality as a result of leukostasis. Leukostasis is a clinical condition characterized by progressive and potentially severe neurologic or respiratory disease attributable to small vessel infiltration and occlusion by leukemic blasts. Hypercalcemia is another disorder that may be associated with a variety of malignant processes. Although relatively rare in children, it may result in a number of life-threatening conditions including cardiac dysrhythmias, neurologic impairment, and renal failure. Additionally, it is well-established that varying degrees of coagulopathy are present in most patients with advanced malignancy. Perhaps most notable, acute promyelocytic leukemia is associated with such a high incidence of death near the time of presentation secondary to intracranial and pulmonary hemorrhages that it is viewed as a medical emergency. Other forms of leukemia may be associated with other pathophysiological consequences that may also be life-threatening. For example, lactic acidosis resulting from a high rate of glycolysis is a very rare, but life-threatening complication of hematologic malignancies. A heightened sense of alertness for these rare conditions may result in earlier detection, more effective therapy, and better outcomes for these children.


Mediastinal mass Hyperleukocytosis Hypercalcemia Acute promyelocytic leukemia Differentiation syndrome Lactic acidosis of malignancy Palliative care Pediatrics 


  1. 1.
    Landis SH, Murray T, Bolden S, et al. Cancer statistics. CA Cancer J Clin. 1999;49:8–31.PubMedCrossRefGoogle Scholar
  2. 2.
    Bleyer WA. The U.S. pediatric cancer clinical trials programmes: international implications and the way forward. Eur J Cancer. 1997;33:1439–47.PubMedCrossRefGoogle Scholar
  3. 3.
    Dalton HJ, Slonim AD, Pollack MM. MultiCenter outcome of pediatric oncology patients requiring intensive care. Pediatr Hematol Oncol. 2003;20:643–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Rosenman MB, Vik T, Hui SL, Breitfeld PP. Hospital resource utilization in childhood cancer. J Pediatr Hematol Oncol. 2005;27:295–300.PubMedCrossRefGoogle Scholar
  5. 5.
    Tamburro RF, West NK, Piercy 4th J, Towner G, Fang HB. Use of the nursing acuity score in children admitted to a pediatric oncology intensive care unit. Pediatr Crit Care Med. 2004;5:35–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Williams HJ, Alton HM. Imaging of paediatric mediastinal abnormalities. Paediatr Respir Rev. 2003;4:55–66.PubMedCrossRefGoogle Scholar
  7. 7.
    Lam JC, Chui CH, Jacobsen AS, Tan AM, Joseph VT. When is a mediastinal mass critical in a child? An analysis of 29 patients. Pediatr Surg Int. 2004;20:180–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Massie RJ, Van Asperen PP, Mellis CM. A review of open biopsy for mediastinal masses. J Paediatr Child Health. 1997;33:230–3.PubMedCrossRefGoogle Scholar
  9. 9.
    King RM, Telander RL, Smithson WA, Banks PM, Han MT. Primary mediastinal tumors in children. J Pediatr Surg. 1982;17:512–20.PubMedCrossRefGoogle Scholar
  10. 10.
    Grosfeld JL, Skinner MA, Rescorla FJ, West KW, Scherer 3rd LR. Mediastinal tumors in children: experience with 196 cases. Ann Surg Oncol. 1994;1:121–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Simpson I, Campbell PE. Mediastinal masses in childhood: a review from a paediatric pathologist’s point of view. Prog Pediatr Surg. 1991;27:92–126.PubMedCrossRefGoogle Scholar
  12. 12.
    King DR, Patrick LE, Ginn-Pease ME, McCoy KS, Klopfenstein K. Pulmonary function is compromised in children with mediastinal lymphoma. J Pediatr Surg. 1997;32:294–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Shamberger RC, Holzman RS, Griscom NT, Tarbell NJ, Weinstein HJ, Wohl ME. Prospective evaluation by computed tomography and pulmonary function tests of children with mediastinal masses. Surgery. 1995;118:468–71.PubMedCrossRefGoogle Scholar
  14. 14.
    Shamberger RC, Holzman RS, Griscom NT, Tarbell NJ, Weinstein HJ. CT quantitation of tracheal cross-sectional area as a guide to the surgical and anesthetic management of children with anterior mediastinal masses. J Pediatr Surg. 1991;26:138–42.PubMedCrossRefGoogle Scholar
  15. 15.
    Azizkhan RG, Dudgeon DL, Buck JR, et al. Life-threatening airway obstruction as a complication to the management of mediastinal masses in children. J Pediatr Surg. 1985;20:816–22.PubMedCrossRefGoogle Scholar
  16. 16.
    Ingram L, Rivera GK, Shapiro DN. Superior vena cava syndrome associated with childhood malignancy: analysis of 24 cases. Med Pediatr Oncol. 1990;18:476–81.PubMedCrossRefGoogle Scholar
  17. 17.
    Keon TP. Death on induction of anesthesia for cervical node biopsy. Anesthesiology. 1981;55:471–2.PubMedCrossRefGoogle Scholar
  18. 18.
    Halpern S, Chatten J, Meadows AT, Byrd R, Lange B. Anterior mediastinal masses: anesthesia hazards and other problems. J Pediatr. 1983;102:407–10.PubMedCrossRefGoogle Scholar
  19. 19.
    Ferrari LR, Bedford RF. General anesthesia prior to treatment of anterior mediastinal masses in pediatric cancer patients. Anesthesiology. 1990;72:991–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Neuman GG, Weingarten AE, Abramowitz RM, Kushins LG, Abramson AL, Ladner W. The anesthetic management of the patient with an anterior mediastinal mass. Anesthesiology. 1984;60:144–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Robie DK, Gursoy MH, Pokorny WJ. Mediastinal tumors–airway obstruction and management. Semin Pediatr Surg. 1994;3:259–66.PubMedGoogle Scholar
  22. 22.
    Bergman NA. Reduction in resting end-expiratory position of the respiratory system with induction of anesthesia and neuromuscular paralysis. Anesthesiology. 1982;57:14–7.PubMedCrossRefGoogle Scholar
  23. 23.
    DeGraff Jr AC, Bouhuys A. Mechanics of air flow in airway obstruction. Annu Rev Med. 1973;24:111–34.PubMedCrossRefGoogle Scholar
  24. 24.
    Ng A, Bennett J, Bromley P, Davies P, Morland B. Anaesthetic outcome and predictive risk factors in children with mediastinal tumours. Pediatr Blood Cancer. 2007;48:160–4.PubMedCrossRefGoogle Scholar
  25. 25.
    Stricker PA, Gurnaney HG, Litman RS. Anesthetic management of children with an anterior mediastinal mass. J Clin Anesth. 2010;22:159–63.PubMedCrossRefGoogle Scholar
  26. 26.
    Perger L, Lee EY, Shamberger RC. Management of children and adolescents with a critical airway due to compression by an anterior mediastinal mass. J Pediatr Surg. 2008;43:1990–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Anghelescu DL, Burgoyne LL, Liu T, et al. Clinical and diagnostic imaging findings predict anesthetic complications in children presenting with malignant mediastinal masses. Paediatr Anaesth. 2007;17:1090–8.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Piro AJ, Weiss DR, Hellman S. Mediastinal Hodgkin’s disease: a possible danger for intubation anesthesia. Intubation danger in Hodgkin’s disease. Int J Radiat Oncol Biol Phys. 1976;1:415–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Goh MH, Liu XY, Goh YS. Anterior mediastinal masses: an anaesthetic challenge. Anaesthesia. 1999;54:670–4.PubMedCrossRefGoogle Scholar
  30. 30.
    Hammer GB. Anaesthetic management for the child with a mediastinal mass. Paediatr Anaesth. 2004;14:95–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Borenstein SH, Gerstle T, Malkin D, Thorner P, Filler RM. The effects of prebiopsy corticosteroid treatment on the diagnosis of mediastinal lymphoma. J Pediatr Surg. 2000;35:973–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Loeffler JS, Leopold KA, Recht A, Weinstein HJ, Tarbell NJ. Emergency prebiopsy radiation for mediastinal masses: impact on subsequent pathologic diagnosis and outcome. J Clin Oncol. 1986;4:716–21.PubMedGoogle Scholar
  33. 33.
    Ebie N, Loew JM, Gregory SA. Bilateral trephine bone marrow biopsy for staging non-Hodgkin’s lymphoma–a second look. Hematol Pathol. 1989;3:29–33.PubMedGoogle Scholar
  34. 34.
    Munker R, Hasenclever D, Brosteanu O, Hiller E, Diehl V. Bone marrow involvement in Hodgkin’s disease: an analysis of 135 consecutive cases. German Hodgkin’s Lymphoma Study Group. J Clin Oncol. 1995;13:403–9.PubMedGoogle Scholar
  35. 35.
    Chaignaud BE, Bonsack TA, Kozakewich HP, Shamberger RC. Pleural effusions in lymphoblastic lymphoma: a diagnostic alternative. J Pediatr Surg. 1998;33:1355–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Wakely Jr PE, Kornstein MJ. Aspiration cytopathology of lymphoblastic lymphoma and leukemia: the MCV experience. Pediatr Pathol Lab Med. 1996;16:243–52.PubMedCrossRefGoogle Scholar
  37. 37.
    Chhieng DC, Cangiarella JF, Symmans WF, Cohen JM. Fine-needle aspiration cytology of Hodgkin disease: a study of 89 cases with emphasis on false-negative cases. Cancer. 2001;93:52–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Demharter J, Muller P, Wagner T, Schlimok G, Haude K, Bohndorf K. Percutaneous core-needle biopsy of enlarged lymph nodes in the diagnosis and subclassification of malignant lymphomas. Eur Radiol. 2001;11:276–83.PubMedCrossRefGoogle Scholar
  39. 39.
    Herman SJ, Holub RV, Weisbrod GL, Chamberlain DW. Anterior mediastinal masses: utility of transthoracic needle biopsy. Radiology. 1991;180:167–70.PubMedCrossRefGoogle Scholar
  40. 40.
    Zinzani PL, Corneli G, Cancellieri A, et al. Core needle biopsy is effective in the initial diagnosis of mediastinal lymphoma. Haematologica. 1999;84:600–3.PubMedGoogle Scholar
  41. 41.
    Glick RD, Pearse IA, Trippett T, Saenz NC, Ginsberg RJ, La Quaglia MP. Diagnosis of mediastinal masses in pediatric patients using mediastinoscopy and the chamberlain procedure. J Pediatr Surg. 1999;34:559–64.PubMedCrossRefGoogle Scholar
  42. 42.
    Tempe DK, Arya R, Dubey S, et al. Mediastinal mass resection: femorofemoral cardiopulmonary bypass before induction of anesthesia in the management of airway obstruction. J Cardiothorac Vasc Anesth. 2001;15:233–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Vas L, Naregal F, Naik V. Anaesthetic management of an infant with anterior mediastinal mass. Paediatr Anaesth. 1999;9:439–43.PubMedCrossRefGoogle Scholar
  44. 44.
    Wickiser JE, Thompson M, Leavey PJ, Quinn CT, Garcia NM, Aquino VM. Extracorporeal membrane oxygenation (ECMO) initiation without intubation in two children with mediastinal malignancy. Pediatr Blood Cancer. 2007;49:751–4.PubMedCrossRefGoogle Scholar
  45. 45.
    Mackie AM, Watson CB. Anaesthesia and mediastinal masses. A case report and review of the literature. Anaesthesia. 1984;39:899–903.PubMedCrossRefGoogle Scholar
  46. 46.
    Mahmoud M, Tyler T, Sadhasivam S. Dexmedetomidine and ketamine for large anterior mediastinal mass biopsy. Paediatr Anaesth. 2008;18:1011–3.PubMedCrossRefGoogle Scholar
  47. 47.
    Polaner DM. The use of heliox and the laryngeal mask airway in a child with an anterior mediastinal mass. Anesth Analg. 1996;82:208–10.PubMedGoogle Scholar
  48. 48.
    Bunin NJ, Pui CH. Differing complications of hyperleukocytosis in children with acute lymphoblastic or acute nonlymphoblastic leukemia. J Clin Oncol. 1985;3:1590–5.PubMedGoogle Scholar
  49. 49.
    Eguiguren JM, Schell MJ, Crist WM, Kunkel K, Rivera GK. Complications and outcome in childhood acute lymphoblastic leukemia with hyperleukocytosis. Blood. 1992;79:871–5.PubMedGoogle Scholar
  50. 50.
    Rowe JM, Lichtman MA. Hyperleukocytosis and leukostasis: common features of childhood chronic myelogenous leukemia. Blood. 1984;63:1230–4.PubMedGoogle Scholar
  51. 51.
    Chim CS, Ooi CG. The irreplaceable image: cerebral leukostasis manifesting as multifocal intracerebral hemorrhage. Haematologica. 2001;86:1231.PubMedGoogle Scholar
  52. 52.
    Kaminsky DA, Hurwitz CG, Olmstead JI. Pulmonary leukostasis mimicking pulmonary embolism. Leuk Res. 2000;24:175–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Porcu P, Cripe LD, Ng EW, et al. Hyperleukocytic leukemias and leukostasis: a review of pathophysiology, clinical presentation and management. Leuk Lymphoma. 2000;39:1–18.PubMedCrossRefGoogle Scholar
  54. 54.
    Stucki A, Rivier AS, Gikic M, Monai N, Schapira M, Spertini O. Endothelial cell activation by myeloblasts: molecular mechanisms of leukostasis and leukemic cell dissemination. Blood. 2001;97:2121–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Wurthner JU, Kohler G, Behringer D, Lindemann A, Mertelsmann R, Lubbert M. Leukostasis followed by hemorrhage complicating the initiation of chemotherapy in patients with acute myeloid leukemia and hyperleukocytosis: a clinicopathologic report of four cases. Cancer. 1999;85:368–74.PubMedCrossRefGoogle Scholar
  56. 56.
    Freireich EJ, Thomas LB, Frei III E, Fritz RD, Forkner Jr CE. A distinctive type of intracerebral hemorrhage associated with “blastic crisis” in patients with leukemia. Cancer. 1960;13:146–54.PubMedCrossRefGoogle Scholar
  57. 57.
    Fritz RD, Forkner Jr CE, Freireich EJ, Frei III E, Thomas LB. The association of fatal intracranial hemorrhage and blastic crisis in patients with acute leukemia. N Engl J Med. 1959;261:59–64.PubMedCrossRefGoogle Scholar
  58. 58.
    Dutcher JP, Schiffer CA, Wiernik PH. Hyperleukocytosis in adult acute nonlymphocytic leukemia: impact on remission rate and duration, and survival. J Clin Oncol. 1987;5:1364–72.PubMedGoogle Scholar
  59. 59.
    Ventura GJ, Hester JP, Smith TL, Keating MJ. Acute myeloblastic leukemia with hyperleukocytosis: risk factors for early mortality in induction. Am J Hematol. 1988;27:34–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Wald BR, Heisel MA, Ortega JA. Frequency of early death in children with acute leukemia presenting with hyperleukocytosis. Cancer. 1982;50:150–3.PubMedCrossRefGoogle Scholar
  61. 61.
    Dearth JC, Fountain KS, Smithson WA, Burgert Jr EO, Gilchrist GS. Extreme leukemic leukocytosis (blast crisis) in childhood. Mayo Clin Proc. 1978;53:207–11.PubMedGoogle Scholar
  62. 62.
    Lowe EJ, Pui CH, Hancock ML, Geiger TL, Khan RB, Sandlund JT. Early complications in children with acute lymphoblastic leukemia presenting with hyperleukocytosis. Pediatr Blood Cancer. 2005;45:10–5.PubMedCrossRefGoogle Scholar
  63. 63.
    Lester TJ, Johnson JW, Cuttner J. Pulmonary leukostasis as the single worst prognostic factor in patients with acute myelocytic leukemia and hyperleukocytosis. Am J Med. 1985;79:43–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Soares RA, Landell GA, Cardoso MC. Pulmonary leukostasis without hyperleukocytosis: a clinicopathologic study of 16 cases. Am J Hematol. 1992;40:28–32.PubMedCrossRefGoogle Scholar
  65. 65.
    Forconi S, Pieragalli D, Guerrini M, Galigani C, Cappelli R. Primary and secondary blood hyperviscosity syndromes, and syndromes associated with blood hyperviscosity. Drugs. 1987;33 Suppl 2:19–26.PubMedCrossRefGoogle Scholar
  66. 66.
    Gertz MA, Kyle RA. Hyperviscosity syndrome. J Intensive Care Med. 1995;10:128–41.PubMedCrossRefGoogle Scholar
  67. 67.
    Lichtman MA, Heal J, Rowe JM. Hyperleukocytic leukaemia: rheological and clinical features and management. Baillieres Clin Haematol. 1987;1:725–46.PubMedCrossRefGoogle Scholar
  68. 68.
    Wells R. Syndromes of hyperviscosity. N Engl J Med. 1970;283:183–6.PubMedCrossRefGoogle Scholar
  69. 69.
    Lichtman MA, Rowe JM. Hyperleukocytic leukemias: rheological, clinical, and therapeutic considerations. Blood. 1982;60:279–83.PubMedGoogle Scholar
  70. 70.
    Steinberg MH, Charm SE. Effect of high concentrations of leukocytes on whole blood viscosity. Blood. 1971;38:299–301.PubMedGoogle Scholar
  71. 71.
    Brown MM, Marshall J. Regulation of cerebral blood flow in response to changes in blood viscosity. Lancet. 1985;1:604–9.PubMedCrossRefGoogle Scholar
  72. 72.
    van Buchem MA, Hogendoorn PC, Levelt CN, et al. Development of pulmonary leukostasis in experimental myelocytic leukemia in the brown-Norway rat. Leukemia. 1992;6:142–9.PubMedGoogle Scholar
  73. 73.
    van Buchem MA, Hogendoorn PC, Bruijn JA, Kluin PM. Endothelial activation antigens in pulmonary leukostasis in leukemia. Acta Haematol. 1993;90:29–33.PubMedCrossRefGoogle Scholar
  74. 74.
    Porcu P, Farag S, Marcucci G, Cataland SR, Kennedy MS, Bissell M. Leukocytoreduction for acute leukemia. Ther Apher. 2002;6:15–23.PubMedCrossRefGoogle Scholar
  75. 75.
    Gartrell K, Rosenstrauch W. Hypoxaemia in patients with hyperleukocytosis: true or spurious, and clinical implications. Leuk Res. 1993;17:915–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Karesh JW, Goldman EJ, Reck K, Kelman SE, Lee EJ, Schiffer CA. A prospective ophthalmic evaluation of patients with acute myeloid leukemia: correlation of ocular and hematologic findings. J Clin Oncol. 1989;7:1528–32.PubMedGoogle Scholar
  77. 77.
    Armitage JO, Goeken JA, Feagler JR. Spurious elevation of the platelet count in acute leukemia. JAMA. 1978;239:433–4.PubMedCrossRefGoogle Scholar
  78. 78.
    Basade M, Dhar AK, Kulkarni SS, et al. Rapid cytoreduction in childhood leukemic hyperleukocytosis by conservative therapy. Med Pediatr Oncol. 1995;25:204–7.PubMedCrossRefGoogle Scholar
  79. 79.
    Harris AL. Leukostasis associated with blood transfusion in acute myeloid leukaemia. Br Med J. 1978;1:1169–71.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Fong C, Fung W, McDonald J, Dalla-Pozza L, De Lima J. Anesthesia for children with hyperleukocytosis a retrospective review. Pediatr Anesth. 2009;19:1191–8.CrossRefGoogle Scholar
  81. 81.
    Maurer HS, Steinherz PG, Gaynon PS, et al. The effect of initial management of hyperleukocytosis on early complications and outcome of children with acute lymphoblastic leukemia. J Clin Oncol. 1988;6:1425–32.PubMedGoogle Scholar
  82. 82.
    Strauss RA, Gloster ES, McCallister JA, Jimenez JF, Neuberg RW, Berry DH. Acute cytoreduction techniques in the early treatment of hyperleukocytosis associated with childhood hematologic malignancies. Med Pediatr Oncol. 1985;13:346–51.PubMedCrossRefGoogle Scholar
  83. 83.
    McLeod BC, Strauss RG, Ciavarella D, et al. Management of hematological disorders and cancer. J Clin Apher. 1993;8:211–30.PubMedCrossRefGoogle Scholar
  84. 84.
    Inaba H, Fan Y, Pounds S, et al. Clinical and biological features and treatment outcome of children with newly diagnosed acute leukemia and hyperleukocytosis. Cancer. 2008;113:522–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Giles FJ, Shen Y, Kantarjian HM, et al. Leukapheresis reduces early mortality in patients with acute myeloid leukemia with high white cell counts but does not improve long-term survival. Leuk Lymphoma. 2001;42:67–73.PubMedCrossRefGoogle Scholar
  86. 86.
    Bug G, Anargyrou K, Tonn T, et al. Impact of leukapheresis on early death rate in adult acute myeloid leukemia presenting with hyperleukocytosis. Transfusion. 2007;47:1843–50.PubMedCrossRefGoogle Scholar
  87. 87.
    Thiébaut A, Thomas X, Belhabri A, Anglaret B, Archimbaud E. Impact of pre-induction therapy leukapheresis on treatment outcome in adult acute myelogenous leukemia presenting with hyperleukocytosis. Ann Hematol. 2000;79:501–6.PubMedCrossRefGoogle Scholar
  88. 88.
    Dombret H, Hunault M, Faucher C, Dombret MC, Degos L. Acute lysis pneumopathy after chemotherapy for acute myelomonocytic leukemia with abnormal marrow eosinophils. Cancer. 1992;69:1356–61.PubMedCrossRefGoogle Scholar
  89. 89.
    Myers TJ, Cole SR, Klatsky AU, Hild DH. Respiratory failure due to pulmonary leukostasis following chemotherapy of acute nonlymphocytic leukemia. Cancer. 1983;51:1808–13.PubMedCrossRefGoogle Scholar
  90. 90.
    Butler RW, Hill JM, Steinherz PG, Meyers PA, Finlay JL. Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer. J Clin Oncol. 1994;12:2621–9.PubMedGoogle Scholar
  91. 91.
    Schmidt JE, Tamburro RF, Sillos EM, Hill DA, Ribeiro RC, Razzouk BI. Pathophysiology-directed therapy for acute hypoxemic respiratory failure in acute myeloid leukemia with hyperleukocytosis. J Pediatr Hematol Oncol. 2003;25:569–71.PubMedCrossRefGoogle Scholar
  92. 92.
    McKay C, Furman WL. Hypercalcemia complicating childhood malignancies. Cancer. 1993;72:256–60.PubMedCrossRefGoogle Scholar
  93. 93.
    Kerdudo C, Aerts I, Fattet S, et al. Hypercalcemia and childhood cancer: a 7-year experience. J Pediatr Hematol Oncol. 2005;27:23–7.PubMedCrossRefGoogle Scholar
  94. 94.
    Leblanc A, Caillaud JM, Hartmann O, et al. Hypercalcemia preferentially occurs in unusual forms of childhood non-Hodgkin’s lymphoma, rhabdomyosarcoma, and Wilms’ tumor. A study of 11 cases. Cancer. 1984;54:2132–6.PubMedCrossRefGoogle Scholar
  95. 95.
    Soni PN. Hypercalcaemia and multiple osteolytic lesions in childhood acute lymphoblastic leukaemia. Postgrad Med J. 1993;69:483–5.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Levendoglu-Tugal O, Kroop S, Rozenblit GN, Weiss R. Primary renal lymphoma and hypercalcemia in a child. Leuk Lymphoma. 2002;43:1141–6.PubMedCrossRefGoogle Scholar
  97. 97.
    Buonuomo PS, Ruggiero A, Piastra M, Riccardi R, Polidori G, Chiaretti A. A case of acute lymphoblastic leukemia presenting as severe hypercalcemia. Pediatr Hematol Oncol. 2004;21:475–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Sultan I, Kraveka JM, Lazarchick J. CD19 negative precursor B acute lymphoblastic leukemia presenting with hypercalcemia. Pediatr Blood Cancer. 2004;43:66–9.PubMedCrossRefGoogle Scholar
  99. 99.
    Stewart AF. Hypercalcemia associated with cancer. N Engl J Med. 2005;352:373–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Mathur M, Sykes JA, Saxena VR, Rao SP, Goldman GM. Treatment of acute lymphoblastic leukemia-induced extreme hypercalcemia with pamidronate and calcitonin. Pediatr Crit Care Med. 2003;4:252–5.PubMedCrossRefGoogle Scholar
  101. 101.
    Lamy O, Jenzer-Closuit A, Burckhardt P. Hypercalcaemia of malignancy: an undiagnosed and undertreated disease. J Intern Med. 2001;250:73–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Diercks DB, Shumaik GM, Harrigan RA, Brady WJ, Chan TC. Electrocardiographic manifestations: electrolyte abnormalities. J Emerg Med. 2004;27:153–60.PubMedCrossRefGoogle Scholar
  103. 103.
    Nierenberg DW, Ransil BJ. Q-aTc interval as a clinical indicator of hypercalcemia. Am J Cardiol. 1979;44:243–8.PubMedCrossRefGoogle Scholar
  104. 104.
    Kearns AE, Khosla S, Kostenuik JP. Receptor activator of nuclear factor kappaB and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2008;29:155–92.PubMedCrossRefGoogle Scholar
  105. 105.
    Mundy GR, Guise TA. Hypercalcemia of malignancy. Am J Med. 1997;103:134–45.PubMedCrossRefGoogle Scholar
  106. 106.
    Clines GA, Guise TA. Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone. Endocrinol Relat Cancer. 2005;12:549–83.CrossRefGoogle Scholar
  107. 107.
    Hewison M, Kantorovich V, Liker HR, et al. Vitamin D-mediated hypercalcemia in lymphoma: evidence for hormone production by tumor-adjacent macrophages. J Bone Miner Res. 2003;18:579–82.PubMedCrossRefGoogle Scholar
  108. 108.
    Lankisch P, Kramm CM, Hermsen D, Wessalowski R. Hypercalcemia with nephrocalcinosis and impaired renal function due to increased parathyroid hormone secretion at onset of childhood acute lymphoblastic leukemia. Leuk Lymphoma. 2004;45:1695–7.PubMedCrossRefGoogle Scholar
  109. 109.
    LeGrand SB, Leskuski D, Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Ann Intern Med. 2008;149:259–63.PubMedCrossRefGoogle Scholar
  110. 110.
    Sargent JT, Smith OP. Haematological emergencies managing hypercalcaemia in adults and children with haematological disorders. Br J Haematol. 2010;149:465–77.PubMedCrossRefGoogle Scholar
  111. 111.
    Fleisch H. Bisphosphonates: mechanisms of action. Endocr Rev. 1998;19:80–100.PubMedCrossRefGoogle Scholar
  112. 112.
    Body JJ, Bartl R, Burckhardt P, et al. Current use of bisphosphonates in oncology. International Bone and Cancer Study Group. J Clin Oncol. 1998;16:3890–9.PubMedGoogle Scholar
  113. 113.
    Hillner BE, Ingle JN, Berenson JR, et al. American society of clinical oncology guideline on the role of bisphosphonates in breast cancer. American society of clinical oncology bisphosphonates expert panel. J Clin Oncol. 2000;18:1378–91.PubMedGoogle Scholar
  114. 114.
    Kutluk MT, Hazar V, Akyuz C, et al. Childhood cancer and hypercalcemia: report of a case treated with pamidronate. J Pediatr. 1997;130:828–31.PubMedCrossRefGoogle Scholar
  115. 115.
    Young G, Shende A. Use of pamidronate in the management of acute cancer-related hypercalcemia in children. Med Pediatr Oncol. 1998;30:117–21.PubMedCrossRefGoogle Scholar
  116. 116.
    Lteif AN, Zimmerman D. Bisphosphonates for treatment of childhood hypercalcemia. Pediatrics. 1998;102:990–3.PubMedCrossRefGoogle Scholar
  117. 117.
    Kutluk T, Akyuz C, Yalcin B, Varan A, Büyükpamuküçu M. Use of pamidronate in the management of acute cancer-related hypercalcemia in children. Med Pediatr Oncol. 1998;31:39.PubMedCrossRefGoogle Scholar
  118. 118.
    Kone Paut I, Gennari JM, Retornaz K, et al. Biphosphonates in children: present and future. Arch Pediatr. 2002;9:836–42.PubMedCrossRefGoogle Scholar
  119. 119.
    Sekine M, Takami H. Combination of calcitonin and pamidronate for emergency treatment of malignant hypercalcemia. Oncol Rep. 1998;5:197–9.PubMedGoogle Scholar
  120. 120.
    Boudailliez BR, Pautard BJ, Sebert JL, Kremp O, Piussan CX. Leukaemia-associated hypercalcaemia in a 10-year-old boy: effectiveness of aminohydroxypropylidene biphosphonate. Pediatr Nephrol. 1990;4:510–1.PubMedCrossRefGoogle Scholar
  121. 121.
    Glorieux FH, Bishop NJ, Plotkin H, et al. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998;339:947–52.PubMedCrossRefGoogle Scholar
  122. 122.
    Shaw NJ, Boivin CM, Crabtree NJ. Intravenous pamidronate in juvenile osteoporosis. Arch Dis Child. 2000;83:143–5.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    August KJ, Dalton A, Katzenstein HM, et al. The use of zoledronic acid in pediatric cancer patients. Pediatr Blood Cancer. 2011;56:610–4.PubMedCrossRefGoogle Scholar
  124. 124.
    Wimalawansa SJ. Significance of plasma PTH-rp in patients with hypercalcemia of malignancy treated with bisphosphonate. Cancer. 1994;73:2223–30.PubMedCrossRefGoogle Scholar
  125. 125.
    Bilezikian JP. Management of acute hypercalcemia. N Engl J Med. 1992;326:1196–203.PubMedCrossRefGoogle Scholar
  126. 126.
    Zojer N, Keck AV, Pecherstorfer M. Comparative tolerability of drug therapies for hypercalcaemia of malignancy. Drug Saf. 1999;21:389–406.PubMedCrossRefGoogle Scholar
  127. 127.
    Leyland-Jones B. Treating cancer-related hypercalcemia with gallium nitrate. J Support Oncol. 2004;2:509–16.PubMedGoogle Scholar
  128. 128.
    Castellano D, Sepulevda JM, Garcia-Escobar I, Rodriquez-Antolin A, Sundlov A, Cortes-Funes H. The role of RANK-ligand inhibition in cancer: the story of denosumab. Oncologist. 2011;16:136–45.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Sarris AH, Kempin S, Berman E, et al. High incidence of disseminated intravascular coagulation during remission induction of adult patients with acute lymphoblastic leukemia. Blood. 1992;79:1305–10.PubMedGoogle Scholar
  130. 130.
    Avvisati G, ten Cate JW, Sturk A, Lamping R, Petti MG, Mandelli F. Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia. Br J Haematol. 1988;70:43–8.PubMedCrossRefGoogle Scholar
  131. 131.
    Humphries JE, Hess CE, Stewart FM. Acute promyelocytic leukemia: impact of hemorrhagic complications on response to induction chemotherapy and survival. South Med J. 1990;83:1157–61.PubMedCrossRefGoogle Scholar
  132. 132.
    De la Serna J, Montesinos P, Vellenga E, et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all transretinoic acid and idarubicin. Blood. 2008;111:3395–402.PubMedCrossRefGoogle Scholar
  133. 133.
    Sanz MA, Montesinos P, Vellenga E, et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy: long-term outcome of the LPA 99 multicenter study by the PETHEMA group. Blood. 2008;112:3130–4.PubMedCrossRefGoogle Scholar
  134. 134.
    Sanz MA, Montesinos P. Open issues on bleeding and thrombosis in acute promyelocytic leukemia. Thromb Res. 2010;125 Suppl 2:S51–4.PubMedCrossRefGoogle Scholar
  135. 135.
    Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113:1875–91.PubMedCrossRefGoogle Scholar
  136. 136.
    Ries LA, Percy CL, Bunin GR. Introduction—SEER pediatric monograph. In: Ries LAG, Smith MA, Gurney JG, Linet M, Tamra T, Young JL, Bunin GR, editors. Cancer incidence and survival among children and adolescents: United States SEER program 1975–1995. Bethesda: National Cancer Institute, SEER Program; 1999. p. 1–15. NIH Pub. No. 99-4649.Google Scholar
  137. 137.
    Kwaan HC, Wang J, Boggio LN. Abnormalities in hemostasis in acute promyelocytic leukemia. Hematol Oncol. 2002;20:33–41.PubMedCrossRefGoogle Scholar
  138. 138.
    Barbui T, Finazzi G, Falanga A, Battista R, Bassan R. Bleeding and thrombosis in acute lymphoblastic leukemia. Leuk Lymphoma. 1993;11 Suppl 2:43–7.PubMedCrossRefGoogle Scholar
  139. 139.
    Federici AB, Falanga A, Lattuada A, Di Rocco N, Barbui T, Mannucci PM. Proteolysis of von Willebrand factor is decreased in acute promyelocytic leukaemia by treatment with all-trans-retinoic acid. Br J Haematol. 1996;92:733–9.PubMedCrossRefGoogle Scholar
  140. 140.
    Falanga A, Rickles FR. Pathogenesis and management of the bleeding diathesis in acute promyelocytic leukaemia. Best Pract Res Clin Haematol. 2003;16:463–82.PubMedCrossRefGoogle Scholar
  141. 141.
    Menell JS, Cesarman GM, Jacovina AT, McLaughlin MA, Lev EA, Hajjar KA. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med. 1999;340:994–1004.PubMedCrossRefGoogle Scholar
  142. 142.
    Falanga A, Marchetti M, Barbui T. All-trans-retinoic acid and bleeding/thrombosis. Pathophysiol Haemost Thromb. 2003;33 Suppl 1:19–21.PubMedCrossRefGoogle Scholar
  143. 143.
    Sanz MA, Tallman MS, Lo-Coco F. Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia. Blood. 2005;105:3019–25.PubMedCrossRefGoogle Scholar
  144. 144.
    Falanga A. Mechanisms of hypercoagulation in malignancy and during chemotherapy. Haemostasis. 1998;28 Suppl 3:50–60.PubMedGoogle Scholar
  145. 145.
    Goldberg MA, Ginsburg D, Mayer RJ, et al. Is heparin administration necessary during induction chemotherapy for patients with acute promyelocytic leukemia? Blood. 1987;69:187–91.PubMedGoogle Scholar
  146. 146.
    Rebulla P, Finazzi G, Marangoni F, et al. The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto. N Engl J Med. 1997;337:1870–5.PubMedCrossRefGoogle Scholar
  147. 147.
    Tallman MS, Kwaan HC. Reassessing the hemostatic disorder associated with acute promyelocytic leukemia. Blood. 1992;79:543–53.PubMedGoogle Scholar
  148. 148.
    Rodeghiero F, Avvisati G, Castaman G, Barbui T, Mandelli F. Early deaths and anti-hemorrhagic treatments in acute promyelocytic leukemia. A GIMEMA retrospective study in 268 consecutive patients. Blood. 1990;75:2112–7.PubMedGoogle Scholar
  149. 149.
    Barbui T, Finazzi G, Falanga A. The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic leukemia. Blood. 1998;91:3093–102.PubMedGoogle Scholar
  150. 150.
    Hashimoto S, Koike T, Tatewaki W, et al. Fatal thromboembolism in acute promyelocytic leukemia during all-trans retinoic acid therapy combined with antifibrinolytic therapy for prophylaxis of hemorrhage. Leukemia. 1994;8:1113–5.PubMedGoogle Scholar
  151. 151.
    Barbui T, Falanga A. Disseminated intravascular coagulation in acute leukemia. Semin Thromb Hemost. 2001;27:593–604.PubMedCrossRefGoogle Scholar
  152. 152.
    Tallman MS, Andersen JW, Schiffer CA, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997;337:1021–8.PubMedCrossRefGoogle Scholar
  153. 153.
    Tallman MS, Andersen JW, Schiffer CA, et al. All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood. 2002;100:4298–302.PubMedCrossRefGoogle Scholar
  154. 154.
    Tallman MS, Andersen JW, Schiffer CA, et al. Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood. 2000;95:90–5.PubMedGoogle Scholar
  155. 155.
    Vahdat L, Maslak P, Miller Jr WH, et al. Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid. Blood. 1994;84:3843–9.PubMedGoogle Scholar
  156. 156.
    De Botton S, Coiteux V, Chevret S, et al. Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy. J Clin Oncol. 2004;22:1404–12.PubMedCrossRefGoogle Scholar
  157. 157.
    Montesinos P, Bergua JM, Vellenga E, et al. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome and prognostic factors. Blood. 2009;113:775–83.PubMedCrossRefGoogle Scholar
  158. 158.
    de Botton S, Dombret H, Sanz M, et al. Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1998;92:2712–8.PubMedGoogle Scholar
  159. 159.
    de Botton S, Chevret S, Coiteux V, et al. Early onset of chemotherapy can reduce the incidence of ATRA syndrome in newly diagnosed acute promyelocytic leukemia (APL) with low white blood cell counts: results from APL 93 trial. Leukemia. 2003;17:339–42.PubMedCrossRefGoogle Scholar
  160. 160.
    Fenaux P, Chastang C, Chevret S, et al. A randomized comparison of all trans retinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. Blood. 1999;94:1192–200.PubMedGoogle Scholar
  161. 161.
    Larson RS, Tallman MS. Retinoic acid syndrome: manifestations, pathogenesis, and treatment. Best Pract Res Clin Haematol. 2003;16:453–61.PubMedCrossRefGoogle Scholar
  162. 162.
    Astudillo L, Loche F, Reynish W, Rigal-Huguet F, Lamant L, Pris J. Sweet’s syndrome associated with retinoic acid syndrome in a patient with promyelocytic leukemia. Ann Hematol. 2002;81:111–4.PubMedCrossRefGoogle Scholar
  163. 163.
    Shirono K, Kiyofuji C, Tsuda H. Sweet’s syndrome in a patient with acute promyelocytic leukemia during treatment with all-trans retinoic acid. Int J Hematol. 1995;62:183–7.PubMedCrossRefGoogle Scholar
  164. 164.
    Nicolls MR, Terada LS, Tuder RM, Prindiville SA, Schwarz MI. Diffuse alveolar hemorrhage with underlying pulmonary capillaritis in the retinoic acid syndrome. Am J Respir Crit Care Med. 1998;158:1302–5.PubMedCrossRefGoogle Scholar
  165. 165.
    Raanani P, Segal E, Levi I, et al. Diffuse alveolar hemorrhage in acute promyelocytic leukemia patients treated with ATRA–a manifestation of the basic disease or the treatment. Leuk Lymphoma. 2000;37:605–10.PubMedCrossRefGoogle Scholar
  166. 166.
    Luesink M, Pennings JL, Wissink WM. Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome. Blood. 2009;114:5512–21.PubMedCrossRefGoogle Scholar
  167. 167.
    Frankel SR, Eardley A, Lauwers G, Weiss M, Warrell Jr RP. The “retinoic acid syndrome” in acute promyelocytic leukemia. Ann Intern Med. 1992;117:292–6.PubMedCrossRefGoogle Scholar
  168. 168.
    Larson RS, Brown DC, Sklar LA. Retinoic acid induces aggregation of the acute promyelocytic leukemia cell line NB-4 by utilization of LFA-1 and ICAM-2. Blood. 1997;90:2747–56.PubMedGoogle Scholar
  169. 169.
    Dubois C, Schlageter MH, de Gentile A, et al. Hematopoietic growth factor expression and ATRA sensitivity in acute promyelocytic blast cells. Blood. 1994;83:3264–70.PubMedGoogle Scholar
  170. 170.
    Tallman MS. All-trans-retinoic acid in acute promyelocytic leukemia and its potential in other hematologic malignancies. Semin Hematol. 1994;31:38–48.PubMedGoogle Scholar
  171. 171.
    Tallman MS. Retinoic acid syndrome: a problem of the past? Leukemia. 2002;16:160–1.PubMedCrossRefGoogle Scholar
  172. 172.
    Fenaux P, Chastang C, Chomienne C, et al. Treatment of newly diagnosed acute promyelocytic leukemia (APL) by all transretinoic acid (ATRA) combined with chemotherapy: the European experience. European APL Group. Leuk Lymphoma. 1995;16:431–7.PubMedCrossRefGoogle Scholar
  173. 173.
    Sanz MA, Martin G, Rayon C, et al. A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RAR alpha-positive acute promyelocytic leukemia. PETHEMA group. Blood. 1999;94:3015–21.PubMedGoogle Scholar
  174. 174.
    Sillos EM, Shenep JL, Burghen GA, Pui CH, Behm FG, Sandlund JT. Lactic acidosis: a metabolic complication of hematologic malignancies: case report and review of the literature. Cancer. 2001;92:2237–46.PubMedCrossRefGoogle Scholar
  175. 175.
    Scheerer PP, Pierre PV, Schwartz DL, Linman JW. Reed-Sternberg-cell leukemia and lactic acidosis. N Engl J Med. 1964;270:274–8.PubMedCrossRefGoogle Scholar
  176. 176.
    de Groot R, Sprenger RA, Imholz AL, Gerding MN. Type B lactic acidosis in solid malignancies. Neth J Med. 2011;69:120–3.PubMedGoogle Scholar
  177. 177.
    Warburg O. On the origin of cancer cells. Science. 1956;123:309–14.PubMedCrossRefGoogle Scholar
  178. 178.
    Mazurek S, Boschek CB, Eigenbrodt E. The role of phosphometabolites in cell proliferation, energy metabolism, and tumor therapy. J Bioenerg Biomembr. 1997;29:315–30.PubMedCrossRefGoogle Scholar
  179. 179.
    Chan FH, Carl D, Lyckholm LJ. Severe lactic acidosis in a patient with B-cell lymphoma: a case report and review of the literature. Case Rep Med. 2009;2009:534561.PubMedGoogle Scholar
  180. 180.
    Ruiz JP, Singh AK, Hart P. Type B lactic acidosis secondary to malignancy: case report, review of published cases, insights into pathogenesis, and prospects for therapy. Sci World J. 2011;11:1316–24.CrossRefGoogle Scholar
  181. 181.
    Fraley DS, Adler S, Bruns FJ, Zett B. Stimulation of lactate production by administration of bicarbonate in a patient with a solid neoplasm and lactic acidosis. N Engl J Med. 1980;303:1100–2.PubMedCrossRefGoogle Scholar
  182. 182.
    Fields AL, Wolman SL, Halperin ML. Chronic lactic acidosis in a patient with cancer: therapy and metabolic consequences. Cancer. 1981;47:2026–9.PubMedCrossRefGoogle Scholar
  183. 183.
    Prikis M, Bhasin V, Young MP, Gennari FJ, Rimmer JM. Sustained low-efficiency dialysis as a treatment modality in a patient with lymphoma-associated lactic acidosis. Nephrol Dial Transplant. 2007;22:2383–5.PubMedCrossRefGoogle Scholar
  184. 184.
    Rabow MW, Hardie GE, Fair JM, McPhee SJ. End-of-life care content in 50 textbooks from multiple specialties. JAMA. 2000;283:771–8.PubMedCrossRefGoogle Scholar
  185. 185.
    Feudtner C, Christakis DA, Zimmerman FJ, Muldoon JH, Neff JM, Koepsell TD. Characteristics of deaths occurring in children’s hospitals: implications for supportive care services. Pediatrics. 2002;109:887–93.PubMedCrossRefGoogle Scholar
  186. 186.
    Wolfe J, Grier HE, Klar N, et al. Symptoms and suffering at the end of life in children with cancer. N Engl J Med. 2000;342:326–33.PubMedCrossRefGoogle Scholar
  187. 187.
    Hilden JM, Emanuel EJ, Fairclough DL, et al. Attitudes and practices among pediatric oncologists regarding end-of-life care: results of the 1998 American Society of Clinical Oncology survey. J Clin Oncol. 2001;19:205–12.PubMedGoogle Scholar
  188. 188.
    Pui CH, Gajjar AJ, Kane JR, Qaddoumi IA, Pappo AS. Challenging issues in pediatric oncology. Nat Rev Clin Oncol. 2011;8:540–9.PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Baker JN, Torkildson C, Baillargeon JG, Olney CA, Kane JR. National survey of pediatric residency program directors and residents regarding education in palliative medicine and end-of-life care. J Palliat Med. 2007;10:420–9.PubMedCrossRefGoogle Scholar
  190. 190.
    Baker JN, Hinds PS, Spunt SL, et al. Integration of palliative care practices into the ongoing care of children with cancer: individualized care planning and coordination. Pediatr Clin N Am. 2008;55:223–50.CrossRefGoogle Scholar
  191. 191.
    Feudtner C, DiGiuseppe DL, Neff JM. Hospital care for children and young adults in the last year of life: a population-based study. BMC Med. 2003;1:3.PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Franco A. Imaging evaluation of pediatric mediastinal masses. Radiol Clin N Am. 2005;43:325–3.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Robert J. Greiner
    • 1
  • Stacey Peterson-Carmichael
    • 2
  • Jennifer A. Rothman
    • 3
  • Kenneth W. Gow
    • 4
  • Robert F. TamburroJr.
    • 5
    Email author
  • Raymond Barfield
    • 6
  1. 1.Division of Hematology/Oncology, Department of PediatricsPenn State Hershey Children’s HospitalHersheyUSA
  2. 2.Divisions of Pediatric Critical Care and Pediatric Pulmonary and Sleep Medicine, Department of PediatricsDuke University Medical CenterDurhamUSA
  3. 3.Department of PediatricsDuke University Medical CenterDurhamUSA
  4. 4.Department of General and Thoracic SurgerySeattle Children’s Hospital, University of WashingtonSeattleUSA
  5. 5.Department of PediatricsPenn State Hershey Children’s HospitalHersheyUSA
  6. 6.Department of Pediatric Hematology/OncologyDuke UniversityDurhamUSA

Personalised recommendations