Annals of Surgical Oncology

, Volume 22, Issue 8, pp 2656–2662 | Cite as

Serious Postoperative Complications Affect Early Recurrence After Cytoreductive Surgery and HIPEC for Colorectal Peritoneal Carcinomatosis

  • Geert A. Simkens
  • Thijs R. van Oudheusden
  • Misha D. Luyer
  • Simon W. Nienhuijs
  • Grard A. Nieuwenhuijzen
  • Harm J. Rutten
  • Ignace H. de HinghEmail author
Colorectal Cancer



The prognosis of patients with peritoneally metastasized colorectal cancer has improved significantly with the introduction of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). Although a macroscopically complete resection is achieved in nearly every patient, recurrence rates are high. This study aims to identify risk factors for early recurrence, thereby offering ways to reduce its occurrence.


All patients with colorectal peritoneal carcinomatosis treated with CRS + HIPEC and a minimum follow-up of 12 months, in April 2014, were analyzed. Patient data were compared between patients with or without recurrence within 12 months after CRS + HIPEC. Risk factors were determined using logistic regression analysis. Postoperative complications were graded according to the serious adverse events (SAEs) score, with grade 3 or higher indicating complications requiring intervention.


A complete macroscopic cytoreduction was achieved in 96 % of all patients treated with CRS + HIPEC. Forty-six of 133 patients (35 %) developed recurrence within 12 months. An SAE ≥3 after CRS + HIPEC was the only significant risk factor found for early recurrence (odds ratio 2.3; p = 0.046). Median survival in the early recurrence group was 19.3 months compared with 43.2 months in the group without early recurrence (p < 0.001). Patients with an SAE ≥3 showed a reduced survival compared with patients without such complications (22.1 vs. 31.0 months, respectively; p = 0.02).


Early recurrence after CRS + HIPEC is associated with a significant reduction in overall survival. This study identifies postoperative complications requiring intervention as the only significant risk factor for early recurrence, independent of the extent of peritoneal disease, highlighting the importance of minimizing the risk of postoperative complications.


Postoperative Complication Peritoneal Carcinomatosis Colorectal Liver Metastasis Cytoreductive Surgery Early Recurrence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No disclosures to report.


  1. 1.
    Kerscher AG, Chua TC, Gasser M, et al. Impact of peritoneal carcinomatosis in the disease history of colorectal cancer management: a longitudinal experience of 2406 patients over two decades. Br J Cancer. 2013;108(7):1432–39.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Lemmens VE, Klaver YL, Verwaal VJ, Rutten HJ, Coebergh JW, de Hingh IH. Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study. Int J Cancer. 2011;128(11):2717–25.PubMedCrossRefGoogle Scholar
  3. 3.
    Chua TC, Morris DL, Saxena A, et al. Influence of modern systemic therapies as adjunct to cytoreduction and perioperative intraperitoneal chemotherapy for patients with colorectal peritoneal carcinomatosis: a multicenter study. Ann Surg Oncol. 2011;18(6):1560–67.PubMedCrossRefGoogle Scholar
  4. 4.
    Klaver YL, Lemmens VE, Creemers GJ, Rutten HJ, Nienhuijs SW, de Hingh IH. Population-based survival of patients with peritoneal carcinomatosis from colorectal origin in the era of increasing use of palliative chemotherapy. Ann Oncol. 2011;22(10):2250–56.PubMedCrossRefGoogle Scholar
  5. 5.
    Klaver YL, Lemmens VE, Nienhuijs SW, Luyer MD, de Hingh IH. Peritoneal carcinomatosis of colorectal origin: Incidence, prognosis and treatment options. World J Gastroenterol. 2012;18(39):5489–94.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    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.PubMedCrossRefGoogle Scholar
  7. 7.
    Glehen O, Kwiatkowski F, Sugarbaker PH, 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(16):3284–92.PubMedCrossRefGoogle Scholar
  8. 8.
    Kuijpers AM, Mirck B, Aalbers AG, et al. Cytoreduction and HIPEC in the Netherlands: nationwide long-term outcome following the Dutch protocol. Ann Surg Oncol. 2013;20(13):4224–30.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Konigsrainer I, Horvath P, Struller F, Forkl V, Konigsrainer A, Beckert S. Risk factors for recurrence following complete cytoreductive surgery and HIPEC in colorectal cancer-derived peritoneal surface malignancies. Langenbecks Arch Surg. 2013;398(5):745–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Braam HJ, van Oudheusden TR, de Hingh IH, et al. Patterns of recurrence following complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. J Surg Oncol. 2014;109(8):841–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13(3):176–81.PubMedCrossRefGoogle Scholar
  12. 12.
    van Oudheusden TR, Braam HJ, Nienhuijs SW, et al. Cytoreduction and hyperthermic intraperitoneal chemotherapy: a feasible and effective option for colorectal cancer patients after emergency surgery in the presence of peritoneal carcinomatosis. Ann Surg Oncol. 2014;21(8):2621–6.PubMedGoogle Scholar
  13. 13.
    Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.PubMedCrossRefGoogle Scholar
  14. 14.
    Baratti D, Kusamura S, Iusco D, et al. Postoperative complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy affect long-term outcome of patients with peritoneal metastases from colorectal cancer: a two-center study of 101 patients. Dis Colon Rectum. 2014;57(7):858–68.PubMedCrossRefGoogle Scholar
  15. 15.
    Goere D, Malka D, Tzanis D, et al. Is there a possibility of a cure in patients with colorectal peritoneal carcinomatosis amenable to complete cytoreductive surgery and intraperitoneal chemotherapy? Ann Surg. 2013;257(6):1065–71.PubMedCrossRefGoogle Scholar
  16. 16.
    Kaibori M, Iwamoto Y, Ishizaki M, et al. Predictors and outcome of early recurrence after resection of hepatic metastases from colorectal cancer. Langenbecks Arch Surg. 2012;397(3):373–81.PubMedCrossRefGoogle Scholar
  17. 17.
    Law WL, Choi HK, Lee YM, Ho JW. The impact of postoperative complications on long-term outcomes following curative resection for colorectal cancer. Ann Surg Oncol. 2007;14(9):2559–66.PubMedCrossRefGoogle Scholar
  18. 18.
    Mirnezami A, Mirnezami R, Chandrakumaran K, Sasapu K, Sagar P, Finan P. Increased local recurrence and reduced survival from colorectal cancer following anastomotic leak: systematic review and meta-analysis. Ann Surg. 2011;253(5):890–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Katoh H, Yamashita K, Wang G, Sato T, Nakamura T, Watanabe M. Anastomotic leakage contributes to the risk for systemic recurrence in stage II colorectal cancer. J Gastrointest Surg. 2011;15(1):120–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.PubMedCrossRefGoogle Scholar
  21. 21.
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45.PubMedCrossRefGoogle Scholar
  22. 22.
    Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Scaife CL, Hartz A, Pappas L, et al. Association between postoperative complications and clinical cancer outcomes. Ann Surg Oncol. 2013;20(13):4063–66.PubMedCrossRefGoogle Scholar
  24. 24.
    Verwaal VJ, Boot H, Aleman BM, van Tinteren H, Zoetmulder FA. Recurrences after peritoneal carcinomatosis of colorectal origin treated by cytoreduction and hyperthermic intraperitoneal chemotherapy: location, treatment, and outcome. Ann Surg Oncol. 2004;11(4):375–79.PubMedCrossRefGoogle Scholar
  25. 25.
    Franko J, Shi Q, Goldman CD, et al. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol. 2012;30(3):263–7.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    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):63–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Passot G, You B, Boschetti G, et al. Pathological response to neoadjuvant chemotherapy: a new prognosis tool for the curative management of peritoneal colorectal carcinomatosis. Ann Surg Oncol. 2014;21(8):2608–14.PubMedCrossRefGoogle Scholar
  28. 28.
    Blazer DG 3rd, Kishi Y, Maru DM, et al. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol. 2008;26(33):5344–51.PubMedCrossRefGoogle Scholar
  29. 29.
    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.CrossRefGoogle Scholar
  30. 30.
    Hompes D, D’Hoore A, Wolthuis A, et al. The use of oxaliplatin or mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. J Surg Oncol. 2014;109(6):527–32.PubMedCrossRefGoogle Scholar
  31. 31.
    Cashin PH, Graf W, Nygren P, Mahteme H. Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis: prognosis and treatment of recurrences in a cohort study. Eur J Surg Oncol. 2012;38(6):509–15.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Geert A. Simkens
    • 1
  • Thijs R. van Oudheusden
    • 1
  • Misha D. Luyer
    • 1
  • Simon W. Nienhuijs
    • 1
  • Grard A. Nieuwenhuijzen
    • 1
  • Harm J. Rutten
    • 1
  • Ignace H. de Hingh
    • 1
    Email author
  1. 1.Department of Surgical OncologyCatharina HospitalEindhovenThe Netherlands

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