Annals of Surgical Oncology

, Volume 23, Issue 7, pp 2315–2322 | Cite as

Cytoreductive Surgery Combined with Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin Increases the Risk of Postoperative Hemorrhagic Complications: Analysis of Predictive Factors

  • Thibaut Charrier
  • Guillaume Passot
  • Julien Peron
  • Christelle Maurice
  • Sashka Gocevska
  • François Quénet
  • Clarisse Eveno
  • Marc Pocard
  • Diane Goere
  • Dominique Elias
  • Pablo Ortega-Deballon
  • Delphine Vaudoyer
  • Eddy Cotte
  • Olivier Glehen
Gastrointestinal Oncology

Abstract

Background

Treatment of peritoneal carcinomatosis (PC) using cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended as curative treatment for selected patients. Modalities of HIPEC remain heterogeneous and HIPEC using oxaliplatin (HIPEC-Ox) appears to increase the risk of postoperative hemorrhagic complications (HCs).

Objective

The aim of this study was to assess the risk of HCs after CRS combined with HIPEC-Ox versus other drugs, and to determine predictive factors for HCs after HIPEC-Ox.

Methods

Data from 701 patients included in the National French Registry who were treated with CRS and HIPEC at 24 centers between 1998 and 2007 were used to evaluate the incidence of HCs following HIPEC with or without oxaliplatin. Overall, 771 patients treated with HIPEC-Ox at five French specialty centers were then analyzed to determine factors associated with the occurrence of HCs.

Results

The overall incidence of HCs was 9.8 %. When used with HIPEC, oxaliplatin significantly and independently increased the rate of HCs (15.7 vs. 2.6 % for other drugs; p = 0.004, odds ratio 32.4). Among the 771 patients who underwent HIPEC-Ox, HCs occurred in 14.3 % of patients. The only independent risk factor for HCs was an extended PC with a Peritoneal Cancer Index (PCI) >12 (p = 0.040).

Conclusion

HIPEC-Ox increases the risk of HCs compared with HIPEC with other drugs. The potential oncologic benefit of oxaliplatin and the risk of HCs should be considered in patients with PC who have a high PCI, as well as in at-risk patients.

References

  1. 1.
    Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2008;15(9):2426–32.CrossRefPubMedGoogle Scholar
  2. 2.
    Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27(5):681–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Esquivel J, Piso P, Verwaal V, et al. American Society of Peritoneal Surface Malignancies opinion statement on defining expectations from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer. J Surg Oncol. 2014;110(7):777–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Esquivel J, Lowy AM, Markman M, et al. The American Society of Peritoneal Surface Malignancies (ASPSM) multiinstitution evaluation of the Peritoneal Surface Disease Severity Score (PSDSS) in 1,013 patients with colorectal cancer with peritoneal carcinomatosis. Ann Surg Oncol. 2014;21(13):4195–201CrossRefPubMedGoogle Scholar
  5. 5.
    Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28(1):63–68.CrossRefPubMedGoogle Scholar
  6. 6.
    Chua TC, Moran B, Sugarbaker PH, et al. Early and long-term outcome data on 2298 patients with pseudomyxoma peritonei of appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy [abstract no. 532]. J Clin Oncol. 2012;30(Suppl 4):2449–56.CrossRefPubMedGoogle Scholar
  7. 7.
    Elias D, Gilly F, Quenet F, et al. Pseudomyxoma peritonei: a French multicentric study of 301 patients treated with cytoreductive surgery and intraperitoneal chemotherapy. Eur J Surg Oncol 2010;36(5):456–62.CrossRefPubMedGoogle Scholar
  8. 8.
    Sugarbaker PH. New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome? Lancet Oncol. 2006;7(1):69–76.CrossRefPubMedGoogle Scholar
  9. 9.
    Yan TD, Deraco M, Baratti D, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009;27(36):6237–42.CrossRefPubMedGoogle Scholar
  10. 10.
    Deraco M, Baratti D, Hutanu I, Bertuli R, Kusamura S. The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2013;20(4):1093–100.CrossRefPubMedGoogle Scholar
  11. 11.
    Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221(1):29–42.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Glehen O, Mohamed F, Gilly FN. Peritoneal carcinomatosis from digestive tract cancer: new management by cytoreductive surgery and intraperitoneal chemohyperthermia. Lancet Oncol. 2004;5:219–28.CrossRefPubMedGoogle Scholar
  13. 13.
    Glehen O, Cotte E, Kusamura S, et al. Hyperthermic intraperitoneal chemotherapy: nomenclature and modalities of perfusion. J Surg Oncol. 2008;98(4):242–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Elias D, Bonnay M, Puizillou JM, et al. Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution. Ann Oncol. 2002;13(2):267–72.CrossRefPubMedGoogle Scholar
  15. 15.
    Elias D, Matsuhisa T, Sideris L, et al. Heated intra-operative intraperitoneal oxaliplatin plus irinotecan after complete resection of peritoneal carcinomatosis: pharmacokinetics, tissue distribution and tolerance. Ann Oncol. 2004;15(10):1558–65.CrossRefPubMedGoogle Scholar
  16. 16.
    Quenet F, Goere D, Mehta SS, et al. Results of two bi-institutional prospective studies using intraperitoneal oxaliplatin with or without irinotecan during HIPEC after cytoreductive surgery for colorectal carcinomatosis. Ann Surg. 2011;254(2):294–301.CrossRefPubMedGoogle Scholar
  17. 17.
    Cotte E, Passot G, Mohamed F, et al. Management of peritoneal carcinomatosis from colorectal cancer: current state of practice. Cancer J. 2009;15(3):243–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Pomel C, Ferron G, Lorimier G, 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(6):589–93.CrossRefPubMedGoogle Scholar
  19. 19.
    Glehen O, Gilly FN, Boutitie F, et al. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. Cancer. 2010;116(24):5608–18.CrossRefPubMedGoogle Scholar
  20. 20.
    Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.CrossRefPubMedGoogle Scholar
  21. 21.
    Verwaal VJ, van Tinteren H, Ruth SV, Zoetmulder FA. Toxicity of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. J Surg Oncol. 2004;85(2):61–67.CrossRefPubMedGoogle Scholar
  22. 22.
    Kusamura S, Younan R, Baratti D, et al. Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion: analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique. Cancer. 2006;106(5):1144–53.CrossRefPubMedGoogle Scholar
  23. 23.
    Gusani NJ, Cho SW, Colovos C, et al. Aggressive surgical management of peritoneal carcinomatosis with low mortality in a high-volume tertiary cancer center. Ann Surg Oncol. 2008;15(3):754–63.CrossRefPubMedGoogle Scholar
  24. 24.
    Iversen LH, Rasmussen PC, Hagemann-Madsen R, Laurberg S. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: the Danish experience. Colorectal Dis. 2013;15(7):e365–72.CrossRefPubMedGoogle Scholar
  25. 25.
    Stephens AD, Alderman R, Chang D, et al. Morbidity and mortality analysis of 200 treatments with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy using the coliseum technique. Ann Surg Oncol. 1999;6(8):790–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Saxena A, Chua TC, Fransi S, Liauw W, Morris DL. Effectiveness of early and aggressive administration of fresh frozen plasma to reduce massive blood transfusion during cytoreductive surgery. J Gastrointest Oncol. 2013;4(1):30–39.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Elias D, Raynard B, Bonnay M, Pocard M. Heated intra-operative intraperitoneal oxaliplatin alone and in combination with intraperitoneal irinotecan: pharmacologic studies. Eur J Surg Oncol. 2006;32(6):607–13.CrossRefPubMedGoogle Scholar
  28. 28.
    Elias D, Goere D, Blot F, et al. Optimization of hyperthermic intraperitoneal chemotherapy with oxaliplatin plus irinotecan at 43 degrees C after compete cytoreductive surgery: mortality and morbidity in 106 consecutive patients. Ann Surg Oncol. 2007;14(6):1818–24.CrossRefPubMedGoogle Scholar
  29. 29.
    Elias D, Honore C, Ciuchendea R, et al. Peritoneal pseudomyxoma: results of a systematic policy of complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Br J Surg. 2008;95(9):1164–71.CrossRefPubMedGoogle Scholar
  30. 30.
    Marcotte E, Sideris L, Drolet P, et al. Hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis arising from appendix: preliminary results of a survival analysis. Ann Surg Oncol. 2008;15(10):2701–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Ceelen WP, Peeters M, Houtmeyers P, et al. Safety and efficacy of hyperthermic intraperitoneal chemoperfusion with high-dose oxaliplatin in patients with peritoneal carcinomatosis. Ann Surg Oncol. 2008;15(2):535–41.CrossRefPubMedGoogle Scholar
  32. 32.
    Quenet F, Elias D, Roca L, et al. Perioperative outcomes of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal carcinomatosis: PRODIGE 7 Randomized Trial [oral presentation]. 22nd Meeting of the European Surgical Association; 8–9 May 2015: Warsaw.Google Scholar
  33. 33.
    Glockzin G, Schlitt HJ, Piso P. Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Surg Oncol.2009;7:5.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Prada-Villaverde A, Esquivel J, Lowy AM, et al. The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with mitomycin C versus oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery. J Surg Oncol. 2014;110(7):779–85.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Thibaut Charrier
    • 1
    • 2
  • Guillaume Passot
    • 1
    • 2
  • Julien Peron
    • 3
  • Christelle Maurice
    • 4
  • Sashka Gocevska
    • 5
  • François Quénet
    • 5
  • Clarisse Eveno
    • 6
  • Marc Pocard
    • 6
  • Diane Goere
    • 7
  • Dominique Elias
    • 7
  • Pablo Ortega-Deballon
    • 8
  • Delphine Vaudoyer
    • 1
    • 2
  • Eddy Cotte
    • 1
    • 2
  • Olivier Glehen
    • 1
    • 2
  1. 1.Department of General SurgeryCentre Hospitalier Lyon SudPierre BéniteFrance
  2. 2.EMR 3738Lyon 1 UniversityLyonFrance
  3. 3.Department of BiostatisticsUMR 5558, Lyon 1 UniversityLyonFrance
  4. 4.Pôle IMER, Unité de Recherche Clinique, Hospices Civils de LyonLyonFrance
  5. 5.Department of SurgeryCentre Val d’AurelleMontpellierFrance
  6. 6.Department of SurgeryHôpital Lariboisière, Assistance-Publique, des hôpitaux de Paris, Paris 7 Université Paris DiderotParisFrance
  7. 7.Department of SurgeryGustave Roussy, Cancer Campus, Grand ParisParisFrance
  8. 8.Department of SurgeryCentre Hospitalier Universitaire de DijonDijonFrance

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