Skip to main content

Advertisement

SpringerLink
Log in

High-grade complication is associated with poor overall survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used in peritoneal carcinomatosis (PC) management. This modality is criticized for its high morbidity and mortality. We evaluate the morbidity and mortality of patients undergoing this procedure in our institution.

Methods

A review of our institution’s database was performed. All patients who underwent CRS/HIPEC between July 2011 and March 2018 were divided into three groups: no, low-grade, and high-grade complications. Prognostic factors were determined with Cox regression, while morbidity risk factors were analyzed using multinomial logistic regression.

Results

225 consecutive patients underwent CRS/HIPEC. The most common primary cancer types were colorectal (35.1%), appendiceal (25.8%), and ovarian (22.2%). Median age was 55 years old (range 14–77), and patients were typically female (68.0%). 38.7% developed low-grade complications and 14.7% had high-grade complications. No 30-day mortality was observed. Different tumor origins are associated with significant differences in overall survival (p < 0.001). Patients without complications had significantly better survival than those with high-grade complications (HR 0.35, 95% CI 0.15–0.81, p < 0.001). Males were more likely to develop low-grade complications (OR 3.30, 95% CI 1.31–8.30, p = 0.011). Intra-operative blood loss was associated with greater odds of developing any post-operative complications (OR 1.001, 95% CI 1.0003–1.002, p = 0.007; and OR 1.002, 95% CI 1.001–1.002, p < 0.001, for low and high grade, respectively).

Conclusion

Presence of high-grade complication was associated with poorer survival in patients after CRS/HIPEC. Pre-operative careful assessment of patients is pivotal to ensure favorable patient outcome following this complex procedure.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Koumpa FS, Xylas D, Konopka M et al (2019) Colorectal peritoneal metastases: a systematic review of current and emerging trends in clinical and translational research. Gastroenterol Res Pract 2019:30. https://doi.org/10.1155/2019/5180895

    Article  Google Scholar 

  2. Coccolini F, Gheza F, Lotti M et al (2013) Peritoneal carcinomatosis. World J Gastroenterol 19(41):6979–6994. https://doi.org/10.3748/wjg.v19.i41.6979

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bristow RE, Puri I, Chi DS (2009) Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol 112(1):265–274. https://doi.org/10.1016/j.ygyno.2008.08.033

    Article  PubMed  Google Scholar 

  4. Glehen O, Osinsky D, Cotte E et al (2003) Intraperitoneal chemohyperthermia using a closed abdominal procedure and cytoreductive surgery for the treatment of peritoneal carcinomatosis: morbidity and mortality analysis of 216 consecutive procedures. Ann Surg Oncol 10(8):863–869

    Article  CAS  PubMed  Google Scholar 

  5. Glehen O, Gilly FN, Boutitie F et al (2010) Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1290 patients. Cancer 116(24):5608–5618. https://doi.org/10.1002/cncr.25356

    Article  PubMed  Google Scholar 

  6. Passot G, Vaudoyer D, Villeneuve L et al (2016) What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: a 25-year experience with 1,125 procedures. J Surg Oncol 113(7):796–803. https://doi.org/10.1002/jso.24248

    Article  PubMed  Google Scholar 

  7. Elias D, Gilly F, Boutitie F et al (2010) Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol 28(1):63–68. https://doi.org/10.1200/JCO.2009.23.9285

    Article  PubMed  Google Scholar 

  8. Elias D, Gilly F, Quenet F et al (2010) Pseudomyxoma peritonei: a French multicentric study of 301 patients treated with cytoreductive surgery and intraperitoneal chemotherapy. Eur J Surg Oncol 36(5):456–462. https://doi.org/10.1016/j.ejso.2010.01.006

    Article  CAS  PubMed  Google Scholar 

  9. Mirnezami R, Mehta AM, Chandrakumaran K et al (2014) Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy improves survival in patients with colorectal peritoneal metastases compared with systemic chemotherapy alone. Br J Cancer 111(8):1500–1508. https://doi.org/10.1038/bjc.2014.419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Huo YR, Richards A, Liauw W et al (2015) Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer: a systematic review and meta-analysis. Eur J Surg Oncol 41(12):1578–1589. https://doi.org/10.1016/j.ejso.2015.08.172

    Article  CAS  PubMed  Google Scholar 

  11. Chia CS, Tan GH, Lim C et al (2016) Prospective quality of life study for colorectal cancer patients with peritoneal carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 23(9):2905–2913. https://doi.org/10.1245/s10434-016-5203-6

    Article  PubMed  Google Scholar 

  12. McQuellon RP, Danhauer SC, Russell GB et al (2007) Monitoring health outcomes following cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis. Ann Surg Oncol 14(3):1105–1113. https://doi.org/10.1245/s10434-006-9304-5

    Article  PubMed  Google Scholar 

  13. Seretis C, Youssef H (2014) Quality of life after cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies: a systematic review. Eur J Surg Oncol 40(12):1605–1613. https://doi.org/10.1016/j.ejso.2014.08.477

    Article  CAS  PubMed  Google Scholar 

  14. Stearns AT, Malcomson L, Punnett G et al (2018) Long-term quality of life after cytoreductive surgery and heated intraperitoneal chemotherapy for pseudomyxoma peritonei: a prospective longitudinal study. Ann Surg Oncol 25(4):965–973. https://doi.org/10.1245/s10434-017-6326-0

    Article  PubMed  Google Scholar 

  15. Verwaal VJ, Bruin S, Boot H et al (2008) 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 15(9):2426–2432. https://doi.org/10.1245/s10434-008-9966-2

    Article  PubMed  Google Scholar 

  16. Yang XJ, Huang CQ, Suo T et al (2011) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol 18(6):1575–1581. https://doi.org/10.1245/s10434-011-1631-5

    Article  PubMed  PubMed Central  Google Scholar 

  17. Spiliotis J, Halkia E, Lianos E et al (2015) Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study. Ann Surg Oncol 22(5):1570–1575. https://doi.org/10.1245/s10434-014-4157-9

    Article  CAS  PubMed  Google Scholar 

  18. van Driel WJ, Koole SN, Sikorska K et al (2018) Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med 378(3):230–240. https://doi.org/10.1056/NEJMoa1708618

    Article  PubMed  Google Scholar 

  19. Chua TC, Yan TD, Saxena A et al (2009) 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 249(6):900–907. https://doi.org/10.1097/SLA.0b013e3181a45d86

    Article  PubMed  Google Scholar 

  20. Levine EA, Stewart JH, Shen P et al (2014) Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1000 patients. J Am Coll Surg 218(4):573–585. https://doi.org/10.1016/j.jamcollsurg.2013.12.013

    Article  PubMed  Google Scholar 

  21. Bartlett EK, Meise C, Roses RE et al (2014) Morbidity and mortality of cytoreduction with intraperitoneal chemotherapy: outcomes from the ACS NSQIP database. Ann Surg Oncol 21(5):1494–1500. https://doi.org/10.1245/s10434-013-3223-z

    Article  PubMed  Google Scholar 

  22. Desantis M, Bernard JL, Casanova V et al (2015) Morbidity, mortality, and oncological outcomes of 401 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC). Langenbecks Arch Surg 400(1):37–48. https://doi.org/10.1007/s00423-014-1253-z

    Article  PubMed  Google Scholar 

  23. Jafari MD, Halabi WJ, Stamos MJ et al (2014) Surgical outcomes of hyperthermic intraperitoneal chemotherapy: analysis of the American college of surgeons national surgical quality improvement program. JAMA Surg 149(2):170–175. https://doi.org/10.1001/jamasurg.2013.3640

    Article  PubMed  Google Scholar 

  24. Tan G, Chia C, Kumar M et al (2016) 201 consecutive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) procedures in a single Asian tertiary centre. Int J Hyperthermia. https://doi.org/10.1080/02656736.2016.1262064

    Article  PubMed  Google Scholar 

  25. Oken MM, Creech RH, Tormey DC et al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5(6):649–656

    Article  CAS  PubMed  Google Scholar 

  26. Sugarbaker PH (1995) Peritonectomy procedures. Ann Surg 221(1):29–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sugarbaker PH, Ronnett BM, Archer A et al (2016) Pseudomyxoma peritonei syndrome. Adv Surg 30:233–280

    Google Scholar 

  28. Sugarbaker PH, Jablonski KA (1995) Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg 221(2):124–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sugarbaker PH (1999) Successful management of microscopic residual disease in large bowel cancer. Cancer Chemother Pharmacol 43(Suppl):S15–S25

    Article  PubMed  Google Scholar 

  30. Patel K, Hadian F, Ali A et al (2016) Postoperative pulmonary complications following major elective abdominal surgery: a cohort study. Perioper Med (London, England) 5:10. https://doi.org/10.1186/s13741-016-0037-0

    Article  Google Scholar 

  31. Fernandez-Bustamante A, Frendl G, Sprung J et al (2017) Postoperative pulmonary complications, early mortality, and hospital stay following noncardiothoracic surgery: a multicenter study by the perioperative research network investigators assessing postoperative pulmonary complications after noncardiothoracic surgery assessing postoperative pulmonary complications after noncardiothoracic surgery. JAMA Surg 152(2):157–166. https://doi.org/10.1001/jamasurg.2016.4065

    Article  PubMed  PubMed Central  Google Scholar 

  32. Cata JP, Zavala AM, Van Meter A et al (2018) Identification of risk factors associated with postoperative acute kidney injury after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a retrospective study. Int J Hyperth 34(5):538–544. https://doi.org/10.1080/02656736.2017.1368096

    Article  Google Scholar 

  33. Tan GHC, Shannon NB, Chia CS et al (2018) Platinum agents and mitomycin C-specific complications in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Int J Hyperth 34(5):595–600. https://doi.org/10.1080/02656736.2017.1345014

    Article  CAS  Google Scholar 

  34. Bouhadjari N, Gabato W, Calabrese D et al (2016) Hyperthermic intraperitoneal chemotherapy with cisplatin: amifostine prevents acute severe renal impairment. Eur J Surg Oncol 42(2):219–223. https://doi.org/10.1016/j.ejso.2015.07.016

    Article  CAS  PubMed  Google Scholar 

  35. Ceresoli M, Coccolini F, Ansaloni L (2016) HIPEC and nephrotoxicity: a cisplatin induced effect? Eur J Surg Oncol 42(6):909–910

    Article  CAS  PubMed  Google Scholar 

  36. Schneider MA, Eshmuminov D, Lehmann K (2017) Major postoperative complications are a risk factor for impaired survival after CRS/HIPEC. Ann Surg Oncol 24(8):2224–2232. https://doi.org/10.1245/s10434-017-5821-7

    Article  PubMed  Google Scholar 

  37. Simkens GA, van Oudheusden TR, Luyer MD et al (2015) Serious postoperative complications affect early recurrence after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis. Ann Surg Oncol 22(8):2656–2662. https://doi.org/10.1245/s10434-014-4297-y

    Article  PubMed  Google Scholar 

  38. Lambert LA, Armstrong TS, Lee JJ et al (2009) Incidence, risk factors, and impact of severe neutropenia after hyperthermic intraperitoneal mitomycin C. Ann Surg Oncol 16(8):2181–2187. https://doi.org/10.1245/s10434-009-0523-4

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tabrizian P, Shrager B, Jibara G et al (2014) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: outcomes from a single tertiary institution. J Gastrointest Surg 18(5):1024–1031. https://doi.org/10.1007/s11605-014-2477-5

    Article  PubMed  Google Scholar 

  40. Rajeev R, Klooster B, Turaga KK (2016) Impact of surgical volume of centers on post-operative outcomes from cytoreductive surgery and hyperthermic intra-peritoneal chemoperfusion. J Gastrointest Oncol 7(1):122–128. https://doi.org/10.3978/j.issn.2078-6891.2015.099

    Article  PubMed  PubMed Central  Google Scholar 

  41. Yan TD, Links M, Fransi S et al (2007) Learning curve for cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal surface malignancy–a journey to becoming a Nationally Funded Peritonectomy Center. Ann Surg Oncol 14(8):2270–2280. https://doi.org/10.1245/s10434-007-9406-8

    Article  PubMed  Google Scholar 

  42. Smeenk RM, Verwaal VJ, Zoetmulder FA (2007) Learning curve of combined modality treatment in peritoneal surface disease. Br J Surg 94(11):1408–1414. https://doi.org/10.1002/bjs.5863

    Article  CAS  PubMed  Google Scholar 

  43. Kuijpers AM, Hauptmann M, Aalbers AG et al (2016) Cytoreduction and hyperthermic intraperitoneal chemotherapy: the learning curve reassessed. Eur J Surg Oncol 42(2):244–250. https://doi.org/10.1016/j.ejso.2015.08.162

    Article  CAS  PubMed  Google Scholar 

  44. Teo MCC, Tan GHC, Tham CK et al (2013) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Asian patients: 100 consecutive patients in a single institution. Ann Surg Oncol 20(9):2968–2974. https://doi.org/10.1245/s10434-013-2947-0

    Article  PubMed  Google Scholar 

  45. Wang W, Tan GHC, Skanthakumar T et al (2018) Exploring the trend in referrals for consideration of CRS and HIPEC to understand the attitudes of clinicians in the development of a national cancer centre programme in peritoneal disease. Int J Hyperthermia 34(5):551–558. https://doi.org/10.1080/02656736.2017.1387939

    Article  PubMed  Google Scholar 

  46. Mise Y, Vauthey JN, Zimmitti G et al (2015) Ninety-day postoperative mortality is a legitimate measure of hepatopancreatobiliary surgical quality. Ann Surg 262(6):1071–1078. https://doi.org/10.1097/sla.0000000000001048

    Article  PubMed  Google Scholar 

  47. Schwarz L, Bruno M, Parker NH et al (2015) Active surveillance for adverse events within 90 days: the standard for reporting surgical outcomes after pancreatectomy. Ann Surg Oncol 22(11):3522–3529. https://doi.org/10.1245/s10434-015-4437-z

    Article  PubMed  Google Scholar 

  48. Alyami M, Kim BJ, Villeneuve L et al (2018) Ninety-day post-operative morbidity and mortality using the National Cancer Institute’s common terminology criteria for adverse events better describe post-operative outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Int J Hyperthermia 34(5):532–537. https://doi.org/10.1080/02656736.2017.1367846

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Ms. Thakshayeni Skanthakumar, database manager; Ms. Li-Lian Kwok, biostatistician.

Author information

Author notes

  1. Joey Wee-Shan Tan and Grace Hwei Ching Tan contributed equally to this work.

Authors and Affiliations

  1. Division of Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610, Singapore

    Joey Wee-Shan Tan, Grace Hwei Ching Tan, Wai Yee Ng, Chin-Ann Johnny Ong, Claramae Shulyn Chia, Khee Chee Soo & Melissa Ching Ching Teo

Authors
  1. Joey Wee-Shan Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Grace Hwei Ching Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wai Yee Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chin-Ann Johnny Ong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Claramae Shulyn Chia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Khee Chee Soo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Melissa Ching Ching Teo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

GHCT and MCCT contributed to the study conception and design. Material preparation, data collection and analysis were performed by JWST and WYN. The first draft of the manuscript was written by JWST and GHCT. CAJO, CSC, KCS and MCCT provided essential clinical and intellectual inputs to the study and reviewed the manuscript critically for publication. All authors commented on previous versions of the manuscript, read and approved the final manuscript.

Corresponding author

Correspondence to Melissa Ching Ching Teo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

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

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tan, J.WS., Tan, G.H.C., Ng, W.Y. et al. High-grade complication is associated with poor overall survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Int J Clin Oncol 25, 984–994 (2020). https://doi.org/10.1007/s10147-019-01609-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-019-01609-5

Keywords

Search

Navigation