Annals of Surgical Oncology

, Volume 26, Issue 5, pp 1445–1453 | Cite as

Repeat Cytoreductive Surgery-Hyperthermic Intraperitoneal Chemoperfusion is Feasible and Offers Survival Benefit in Select Patients with Peritoneal Metastases

  • Haroon A. ChoudryEmail author
  • Filip Bednar
  • Yongli Shuai
  • Heather L. Jones
  • Reetesh K. Pai
  • James F. Pingpank
  • Steven S. Ahrendt
  • Matthew P. Holtzman
  • Herbert J. Zeh
  • David L. Bartlett
Peritoneal Surface Malignancy



We hypothesized that repeat cytoreductive surgery-hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) for peritoneal metastases (PM) may be associated with suboptimal resection, more frequent postoperative complications, and worse oncologic outcomes.


Using a prospectively maintained database, we compared clinicopathologic, perioperative, and oncologic outcome data in patients undergoing single or repeat CRS-HIPEC procedures. The Kaplan–Meier method was used to estimate survival. Multivariate analyses identified associations with perioperative and oncologic outcomes.


Of the 1294 patients undergoing CRS-HIPEC procedures at our institution, only one CRS-HIPEC procedure (single HIPEC cohort) was performed in 1169 patients (90.3%), whereas 125 patients (9.7%) underwent repeat CRS-HIPEC procedures (repeat HIPEC cohort). Of the 1440 CRS-HIPEC procedures at our institution, a first CRS-HIPEC procedure was performed in 1294 patients (89.9%), whereas subsequent second, third, and fourth CRS-HIPEC procedures were performed in 125 patients (8.7%), 18 patients (1.3%), and 3 patients (0.2%), respectively. Progression-free survival (PFS) following the second CRS-HIPEC procedure was negatively impacted by shorter PFS following the first CRS-HIPEC procedure, independent of other significant variables related to the second procedure, including completeness of cytoreduction and postoperative complications. Patients undergoing multiple CRS-HIPEC procedures were not at higher risk for suboptimal resection or postoperative complications and demonstrated equivalent PFS following each successive procedure compared to the first procedure.


Repeat CRS-HIPEC procedures for PM were not associated with suboptimal perioperative and oncologic outcomes. Our data confirmed our ability to select patients appropriately for repeat CRS-HIPEC procedures.



This work was partially funded by generous support from Valarie Koch and the New Era Cap Company. The project was supported by the National Institutes of Health through Grant Number UL1-TR-001857, using a Red cap maintained database.




  1. 1.
    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.CrossRefGoogle Scholar
  2. 2.
    Levine EA, Stewart JHt, Shen P, Russell GB, Loggie BL, Votanopoulos KI. Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1,000 patients. J Am Coll Surg. 2014;218(4):573–85.CrossRefGoogle Scholar
  3. 3.
    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.CrossRefGoogle Scholar
  4. 4.
    Yan TD, Black D, Savady R, Sugarbaker PH. A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei. Ann Surg Oncol. 2007;14(2):484–92.CrossRefGoogle Scholar
  5. 5.
    Yan TD, Welch L, Black D, Sugarbaker PH. A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Ann Oncol. 2007;18(5):827–34.CrossRefGoogle Scholar
  6. 6.
    Brouquet A, Goere D, Lefevre JH, et al. The second procedure combining complete cytoreductive surgery and intraperitoneal chemotherapy for isolated peritoneal recurrence: postoperative course and long-term outcome. Ann Surg Oncol. 2009;16(10):2744–51.CrossRefGoogle Scholar
  7. 7.
    Chua TC, Moran BJ, Sugarbaker PH, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012;30(20):2449–56.CrossRefGoogle Scholar
  8. 8.
    Deraco M, Nonaka D, Baratti D, et al. Prognostic analysis of clinicopathologic factors in 49 patients with diffuse malignant peritoneal mesothelioma treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Ann Surg Oncol. 2006;13(2):229–37.CrossRefGoogle Scholar
  9. 9.
    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):375–9.CrossRefGoogle Scholar
  10. 10.
    Votanopoulos KI, Ihemelandu C, Shen P, Stewart JH, Russell GB, Levine EA. Outcomes of repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal surface malignancy. J Am Coll Surg. 2012;215(3):412–7.CrossRefGoogle Scholar
  11. 11.
    Yan TD, Bijelic L, Sugarbaker PH. Critical analysis of treatment failure after complete cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal dissemination from appendiceal mucinous neoplasms. Ann Surg Oncol. 2007;14(8):2289–99.CrossRefGoogle Scholar
  12. 12.
    Konstantinidis IT, Levine EA, Chouliaras K, Russell G, Shen P, Votanopoulos KI. Interval between cytoreductions as a marker of tumor biology in selecting patients for repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2017;116(6):741–5.CrossRefGoogle Scholar
  13. 13.
    Mogal H, Chouliaras K, Levine EA, Shen P, Votanopoulos KI. Repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: review of indications and outcomes. J Gastrointest Oncol. 2016;7(1):129-42.Google Scholar
  14. 14.
    Vassos N, Fortsch T, Aladashvili A, Hohenberger W, Croner RS. Repeated cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with recurrent peritoneal carcinomatosis. World J Surg Oncol. 2016;14(1):42.CrossRefGoogle Scholar
  15. 15.
    Golse N, Bakrin N, Passot G, et al. Iterative procedures combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal recurrence: postoperative and long-term results. J Surg Oncol. 2012;106(2):197–203.CrossRefGoogle Scholar
  16. 16.
    Wong JF, Tan GH, Wang W, Soo KC, Teo MC. Repeat Cytoreductive Surgery and HIPEC for Peritoneal Surface Malignancy and Peritoneal Carcinomatosis. World J Surg. 2015;39(6):1578–83.CrossRefGoogle Scholar
  17. 17.
    Ihemelandu C, Bijelic L, Sugarbaker PH. Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome. Ann Surg Oncol. 2015;22(5):1680–5.CrossRefGoogle Scholar
  18. 18.
    Aoyama T, Oba K, Honda M, et al. Impact of postoperative complications on the colorectal cancer survival and recurrence: analyses of pooled individual patients’ data from three large phase III randomized trials. Cancer Med. 2017;6(7):1573–80.CrossRefGoogle Scholar
  19. 19.
    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.CrossRefGoogle Scholar
  20. 20.
    Binkowska AM, Michalak G, Slotwinski R. Current views on the mechanisms of immune responses to trauma and infection. Cent Eur J Immunol. 2015;40(2):206–16.CrossRefGoogle Scholar
  21. 21.
    Lee L, Alie-Cusson F, Dube P, Sideris L. Postoperative complications affect long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. J Surg Oncol. 2017;116(2):236–43.CrossRefGoogle Scholar
  22. 22.
    Roxburgh CS, Horgan PG, McMillan DC. The perioperative immune/inflammatory insult in cancer surgery: Time for intervention? Oncoimmunology. 2013;2(12):e27324.CrossRefGoogle Scholar
  23. 23.
    Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.CrossRefGoogle Scholar
  24. 24.
    Bao P, Bartlett D. Surgical techniques in visceral resection and peritonectomy procedures. Cancer J. 2009;15(3):204–11.CrossRefGoogle Scholar
  25. 25.
    Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96.CrossRefGoogle Scholar
  26. 26.
    Davison JM, Choudry HA, Pingpank JF, et al. Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade. Mod Pathol. 2014;27(11):1521–39.CrossRefGoogle Scholar
  27. 27.
    Tang LH, Shia J, Soslow RA, et al. Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix. Am J Surg Pathol. 2008;32(10):1429–43.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Haroon A. Choudry
    • 1
    Email author
  • Filip Bednar
    • 1
  • Yongli Shuai
    • 3
  • Heather L. Jones
    • 1
  • Reetesh K. Pai
    • 2
  • James F. Pingpank
    • 1
  • Steven S. Ahrendt
    • 1
  • Matthew P. Holtzman
    • 1
  • Herbert J. Zeh
    • 1
  • David L. Bartlett
    • 1
  1. 1.Division of Surgical OncologyKoch Regional Perfusion Center, University of PittsburghPittsburghUSA
  2. 2.Department of PathologyUniversity of PittsburghPittsburghUSA
  3. 3.The University of Pittsburgh Cancer Institute Biostatistics FacilityPittsburghUSA

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