Hemophagocytic Syndrome: An Unusual and Underestimated Complication of Cytoreduction Surgery with Heated Intraperitoneal Oxaliplatin
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Hyperthermic intraperitoneal chemotherapy (HIPEC) improves the survival of select patients with peritoneal carcinomatosis. Hemophagocytic syndrome (HS) is a rare and potentially fatal disease. We describe our experience with five patients who developed HS following oxaliplatin HIPEC and propose a management procedure.
Hyperthermic intraperitoneal chemotherapy was performed using the open-abdomen technique (43 °C) with oxaliplatin (460 mg/m 2 ) for 30 min. If thrombocytopenia occurred from days 5 to 14, heparin-induced thrombocytopenia was evaluated. For thrombocytopenia with unknown etiology, we performed a bone marrow analysis (BMA). A BMA indicating HS stimulated an extensive infectious disease workup. Herein, we describe “reactive septic HS” and HS of unknown origin.
We documented five patients with HS as a result of severe thrombocytopenia. Underlying infections were present in two patients who were treated with antibiotics and survived. For the remaining three patients, we found no underlying etiology of HS; multidisciplinary staff adapted the clinical management daily. Two patients died on postoperative days 40 and 29. The third patient survived after several operations and treatment with the VAC abdominal dressing system.
We present these cases to ensure that physicians are aware of the symptoms of HS after HIPEC, which are important for initiating immediate life-saving therapy. This condition is a diagnostic and therapeutic emergency. When HS complicates HIPEC, aggressive, early medical, and surgical management is required. However, the optimal management has not been defined.
- Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737–43. CrossRef
- Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22:3284–92. CrossRef
- Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27:681–5. CrossRef
- Yan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27:6237–42. CrossRef
- Chua TC, Yan TD, Saxena A, Morris DL. Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure?: a systematic review of morbidity and mortality. Ann Surg. 2009;249:900–7. CrossRef
- Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg. 2006;10:1199–210; discussion 1210–1. CrossRef
- Elias D, Raynard B, Boige V, Laplanche A, Estphan G, Malka D, et al. Impact of the extent and duration of cytoreductive surgery on postoperative hematological toxicity after intraperitoneal chemohyperthermia for peritoneal carcinomatosis. J Surg Oncol. 2005;90:220–5. CrossRef
- Elias D, El Otmany A, Bonnay M, Paci A, Ducreux M, Antoun S, et al. Human pharmacokinetic study of heated intraperitoneal oxaliplatin in increasingly hypotonic solutions after complete resection of peritoneal carcinomatosis. Oncology. 2002;63:346–52. CrossRef
- Pomel C, Ferron G, Lorimier G, Rey A, Lhomme C, Classe JM, et al. Hyperthermic intra-peritoneal chemotherapy using oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma: results of a phase II prospective multicentre trial. CHIPOVAC study. Eur J Surg Oncol. 2010;36:589–93. CrossRef
- Jacquet P, Sugarbaker PH. Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J Exp Clin Cancer Res. 1996;15:49–58.
- Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221:29–42. CrossRef
- Elias D, Bonnay M, Puizillou JM, Antoun S, Demirdjian S, El OA, et al. Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution. Ann Oncol. 2002;13:267–72. CrossRef
- Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–31. CrossRef
- NCI. CTEP: NCI Guidance on CTC Terminology Applications. Bethesda, MD: National Cancer Institute. 2009. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 1 March 2013.
- Jardim DL, Rodrigues CA, Novis YA, Rocha VG, Hoff PM. Oxaliplatin-related thrombocytopenia. Ann Oncol. 2012;23:1937–42. CrossRef
- Votanopoulos K, Ihemelandu C, Shen P, Stewart J, Russell G, Levine EA. A comparison of hematologic toxicity profiles after heated intraperitoneal chemotherapy with oxaliplatin and mitomycin C. J Surg Res. 2013;179:e133–9. CrossRef
- Sugarbaker PH, Alderman R, Edwards G, Marquardt CE, Gushchin V, Esquivel J, et al. Prospective morbidity and mortality assessment of cytoreductive surgery plus perioperative intraperitoneal chemotherapy to treat peritoneal dissemination of appendiceal mucinous malignancy. Ann Surg Oncol. 2006;13:635–44. CrossRef
- Shao YY, Hong RL. Fatal thrombocytopenia after oxaliplatin-based chemotherapy. Anticancer Res. 2008;28:3115–7.
- Curtis BR, Kaliszewski J, Marques MB, Saif MW, Nabelle L, Blank J, et al. Immune-mediated thrombocytopenia resulting from sensitivity to oxaliplatin. Am J Hematol. 2006;81:193–8. CrossRef
- Bautista MA, Stevens WT, Chen CS Curtis BR, Aster RH, Hsueh CT. Hypersensitivity reaction and acute immune-mediated thrombocytopenia from oxaliplatin: two case reports and a review of the literature. J Hematol Oncol. 2010;3:12. CrossRef
- Hoff PM, Saad ED, Costa F, Coutinho AK, Caponero R, Prolla G, et al. Literature review and practical aspects on the management of oxaliplatin-associated toxicity. Clin Colorectal Cancer. 2012;11:93–100.
- Janka GE. Hemophagocytic syndromes. Blood Rev. 2007;21:245–53. CrossRef
- Schneider EM, Lorenz I, Muller-Rosenberger M, Steinbach G, Kron M, Janka-Schaub GE. Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell-induced apoptosis. Blood. 2002;100:2891–8. CrossRef
- Henter JI, Elinder G, Soder O, Hansson M, Andersson B, Andersson U. Hypercytokinemia in familial hemophagocytic lymphohistiocytosis. Blood. 1991;78:2918–22.
- Francois B, Trimoreau F, Vignon P, Fixe P, Praloran V, Gastinne H. Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage colony-stimulating factor. Am J Med. 1997;103:114–20. CrossRef
- Trimoreau F, Francois B, Desachy A, Besse A, Vignon P, Denizot Y. Platelet-activating factor acetylhydrolase and haemophagocytosis in the sepsis syndrome. Mediat Inflamm. 2000;9:197–200. CrossRef
- Fisman DN. Hemophagocytic syndromes and infection. Emerg Infect Dis. 2000;6:601–8. CrossRef
- Tsuda H. Hemophagocytic syndrome (HPS) in children and adults. Int J Hematol. 1997;65:215–26. CrossRef
- Imashuku S. Advances in the management of hemophagocytic lymphohistiocytosis. Int J Hematol. 2000;72:1–11.
- Imashuku S, Kuriyama K, Teramura T, Ishii E, Kinugawa N, Kato M, et al. Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Clin Oncol. 2001;19:2665–73.
- Tateishi Y, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Abe R, et al. Continuous hemodiafiltration in the treatment of reactive hemophagocytic syndrome refractory to medical therapy. Transfus Apher Sci. 2009;40:33–40. CrossRef
- Hemophagocytic Syndrome: An Unusual and Underestimated Complication of Cytoreduction Surgery with Heated Intraperitoneal Oxaliplatin
Annals of Surgical Oncology
Volume 20, Issue 12 , pp 3919-3926
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- Springer US
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- 1. Department of Digestive Surgery, Hôpital Charles Nicolle, Rouen Cedex, France
- 2. Surgical Intensive Care Unit, Hôpital Charles Nicolle, Rouen Cedex, France
- 3. Department of Clinical Immunology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, University Paris Diderot, Paris, France
- 4. Department of Anaesthesiology, Hôpital Charles Nicolle, Rouen Cedex, France