Skip to main content
Log in

Elevated Maximum Core Body Temperature During Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) is Associated with Increased Postoperative Complications

  • Peritoneal Surface Malignancy
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Hyperthermia enhances the cytotoxicity of chemotherapeutic agents used during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC). However, this may result in an elevated core body temperature (CBT), with unintended effects on surgical morbidity. This study evaluates the relationship of maximum CBT during CRS/HIPEC on postoperative outcomes.

Methods

A retrospective review of patients undergoing CRS/HIPEC from January 2011 to July 2017 was performed. Outcomes were stratified according to maximum CBT reached during HIPEC. Primary study endpoints were 30-day morbidity and 30-day complication severity.

Results

Overall, 135 consecutive CRS/HIPEC cases were reviewed; 36 (27%) had a maximum CBT ≥ 39.5 °C during the 90-min HIPEC. CBT ≥ 39.5 °C was associated with an increase in 30-day postoperative complications (58% vs. 34%, p = 0.01) and severe Clavien–Dindo grade III or higher complications (22% vs. 11%, p = 0.04). On multivariate analysis, the adjusted odds ratio of having any complication was 3.77 (95% confidence interval [CI] 1.56–9.14) and a Clavien–Dindo grade III or higher complication was 3.46 (95% CI 1.10–10.95) when maximum CBT reached 39.5 °C. Flow rates ≥ 2.35 L/min were associated with lower average CBT (p = 0.05) and improved peritoneal heating (p = 0.02).

Conclusion

Maximum CBT ≥ 39.5 °C is associated with an increased risk of postoperative morbidity. Higher flow rates are associated with improved intraperitoneal heating, lower CBT, and may contribute to optimizing the therapeutic benefit of HIPEC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  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;22:3284–92.

    Article  CAS  Google Scholar 

  2. 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;116:5608–18.

    Article  Google Scholar 

  3. Sugarbaker PH. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of gastrointestinal cancers with peritoneal metastases: progress toward a new standard of care. Cancer Treat Rev. 2016;48:42–9.

    Article  Google Scholar 

  4. Cao C, Yan TD, Black D, et al. A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2009;16:2152–65.

    Article  Google Scholar 

  5. Smeenk RM, Verwaal VJ, Antonini N, et al. Survival analysis of pseudomyxoma peritonei patients treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg. 2007;245:104-9.

    Article  Google Scholar 

  6. Sugarbaker PH, Chang D. Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy. Ann Surg Oncol. 1999;6:727–31.

    Article  CAS  Google Scholar 

  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;36:456–62.

    Article  CAS  Google Scholar 

  8. Sugarbaker PH. Laboratory and clinical basis for hyperthermia as a component of intracavitary chemotherapy. Int J Hyperthermia. 2007;23:431–42.

    Article  CAS  Google Scholar 

  9. Dewhirst MW, Viglianti BL, Lora-Michiels M, Hanson M, Hoopes PJ. Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia. Int J Hyperthermia. 2003;19(3):267–94.

    Article  CAS  Google Scholar 

  10. Ohno S, Siddik ZH, Kido Y, Zwelling LA, Bull JMC. Thermal enhancement of drug uptake and DNA adducts as a possible mechanism for the effect of sequencing hyperthermia on cisplatin-induced cytotoxicity in L1210 cells. Cancer Chemother Pharmacol. 1994;34:302–6.

    Article  CAS  Google Scholar 

  11. Song C, Park HJ, Lee CK, Griffin R. Implications of increased tumor blood flow and oxygenation caused by mild temperature hyperthermia in tumor treatment. Int J Hyperthermia 2005;21(8):761–768.

    Article  CAS  Google Scholar 

  12. Horsman MR. Tissue physiology and the response to heat. Int J Hyperthermia. 2006;22(3):197–203.

    Article  Google Scholar 

  13. Frey B, Weiss EM, Rubner Y, et al. Old and new facts about hyperthermia-induced modulations of the immune system. Int J Hyperthermia. 2012;28:528–42.

    Article  CAS  Google Scholar 

  14. Skitzki JJ, Repasky EA, Evans SS. Hyperthermia as an immunotherapy strategy for cancer. Curr Opin Investig Drugs. 2009;10:550–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Hildebrandt B, Wust P, Ahlers O, et al. The cellular and molecular basis of hyperthermia. Crit Rev Oncol Hematol. 2002;43:33–56.

    Article  Google Scholar 

  16. User Guide for the 2016 ACS NSQIP Participant Use Data File. American College of Surgeons National Surgical Quality Improvement Program; Oct 2017. pp. 15–8.

  17. Dindo D, Demartines N, Clavien P. classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients. Ann Surg. 2004;240(2):205–13.

    Article  Google Scholar 

  18. Spratt JS, Adcock RA, Muskovin M, et al. Clinical delivery system for intraperitoneal hyperthermic chemotherapy. Cancer Res. 1980;40:256–60.

    CAS  PubMed  Google Scholar 

  19. Koga S, Hamazoe R, Maeta M, Shimizu N, Kanayama H, Osaki Y. Treatment of implanted peritoneal cancer in rats by continuous hyperthermic peritoneal perfusion. Cancer Res. 1984;44:1840–2.

    CAS  PubMed  Google Scholar 

  20. Koga S, Hamazoe R, Maeta M, Shimizu N, Murakami A, Wakatsuki T. Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C. Cancer. 1988;61:232–7.

    Article  CAS  Google Scholar 

  21. Verwaal VJ, Bruin S, Boot H, et al. 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;15:2426–32.

    Article  Google Scholar 

  22. 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.

    Article  Google Scholar 

  23. Chua T, Moran B, Sugarbaker P, 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;30:2449–56.

    Article  Google Scholar 

  24. Schaaf L, Kuip H, Zopf W, et al. A temperature of 40°C appears to be a critical threshold for potentiating cytotoxic chemotherapy in vitro and in peritoneal carcinomatosis patients undergoing HIPEC. Ann Surg Oncol. 2015;22:758–65.

    Article  Google Scholar 

  25. Goldenshluger M, Zippel D, Ben-Yaacov A, et al. Core body temperature but not intraabdominal pressure predicts postoperative complications following closed system hyperthermic intraperitoneal chemotherapy (HIPEC) administration. Ann Surg Oncol. 2018;25:660–6.

    Article  CAS  Google Scholar 

  26. Furman MJ, Picotte RJ, Wante MJ, et al. Higher flow rates improve heating during hyperthermic intraperitoneal chemoperfusion. J Surg Oncol. 2014;110:970–5.

    Article  Google Scholar 

Download references

Acknowledgment

The data for this research were provided by the Cancer Research Office of the University of Massachusetts Medical Center.

Funding

Funding for this study was provided by the Division of Surgical Oncology at the University of Massachusetts Medical School.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Laura A. Lambert MD, FACS.

Ethics declarations

Disclosures

Ryan J. Hendrix, Jonathan P. Kassira, and Laura A. Lambert have no disclosures to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hendrix, R.J., Kassira, J.P. & Lambert, L.A. Elevated Maximum Core Body Temperature During Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) is Associated with Increased Postoperative Complications. Ann Surg Oncol 27, 232–239 (2020). https://doi.org/10.1245/s10434-019-07495-5

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-019-07495-5

Navigation