Epidemiology and risks for infection following cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy

Abstract

Background

CRS-HIPEC is associated with improved cancer survival but an increased risk of infection.

Methods

Consecutive patients undergoing CRS-HIPEC between January 2016 and May 2018 were retrospectively reviewed. Malignancy type, comorbidities, perioperative risk factors and infectious complications were captured, using standardised definitions. Association between risk factors and infection outcomes was evaluated by logistic regression modelling.

Results

One-hundred patients underwent CRS-HIPEC, predominantly for colorectal cancer and pseudomyxoma peritonei. Overall, 43 (43.0%) experienced an infectious complication, including infections at surgical site (27), respiratory tract (9), urinary tract (11), Clostridium difficile (2) and post-operative sepsis (15). In most, infection onset was within 7 days post-operatively. Median length of hospitalisation was 19 days for patients with infection, compared to 8 days for those without (p = 0.000). There were no deaths at 60 days. Of variables potentially associated with surgical site infection, small bowel resection (OR 4.01, 95% confidence interval [CI] 1.53–10.83; p = 0.005) and number of resected viscera (OR 1.41, 95% CI 1.00–1.98; p = 0.048) were significantly associated with infection.

Conclusions

We demonstrate a significant burden of early infective complications in patients undergoing CRS-HIPEC. Higher-risk subgroups, including those with small bowel resection and increased number of resected viscera, may benefit from enhanced monitoring.

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References

  1. 1.

    Chua TC, Yan TD, Saxena A, Morris DL (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

    Article  Google Scholar 

  2. 2.

    Glehen O, Gilly FN, Boutitie F, Bereder JM, Quenet F, Sideris L, Mansvelt B, Lorimier G, Msika S, Elias D, French Surgical Association (2010) 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. 116(24):5608–5618

    Article  Google Scholar 

  3. 3.

    Jafari MD, Halabi WJ, Stamos MJ, Nguyen VQ, Carmichael JC, Mills SD, Pigazzi A (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

    Article  Google Scholar 

  4. 4.

    Kuijpers AM, Mirck B, Aalbers AG, Nienhuijs SW, de Hingh IH, Wiezer MJ, van Ramshorst B, van Ginkel R, Havenga K, Bremers AJ, de Wilt JH, te Velde EA, Verwaal VJ (2013) Cytoreduction and HIPEC in the Netherlands: nationwide long-term outcome following the Dutch protocol. Ann Surg Oncol 20(13):4224–4230

    Article  Google Scholar 

  5. 5.

    Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA (2003) Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol : official journal of the American Society of Clinical Oncology. 21(20):3737–3743

    Article  Google Scholar 

  6. 6.

    Pamela K, Matthias Z, Reinhold KR, Julia P, Peter M, Alexander P, et al. (2018) Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): a single-center experience in Austria. J Gastrointest Surg : official journal of the Society for Surgery of the Alimentary Tract

  7. 7.

    Tan G, Chia C, Kumar M, Choo SP, Chia J, Tham CK, et al. (2016) 201 consecutive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) procedures in a single Asian tertiary centre. Int J Hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group:1-7

  8. 8.

    Spiliotis J, Halkia E, de Bree E (2016) Treatment of peritoneal surface malignancies with hyperthermic intraperitoneal chemotherapy-current perspectives. Current oncology (Toronto, Ont) 23(3):e266–e275

    CAS  Article  Google Scholar 

  9. 9.

    Polanco PM, Ding Y, Knox JM, Ramalingam L, Jones H, Hogg ME, Zureikat AH, Holtzman MP, Pingpank J, Ahrendt S, Zeh HJ, Bartlett DL, Choudry HA (2015) Institutional learning curve of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for peritoneal malignancies. Ann Surg Oncol 22(5):1673–1679

    Article  Google Scholar 

  10. 10.

    Lee L, Alie-Cusson F, Dube P, Sideris L (2017) Postoperative complications affect long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. J Surg Oncol 116(2):236–243

    CAS  Article  Google Scholar 

  11. 11.

    Feldheiser A, Aziz O, Baldini G, Cox BP, Fearon KC, Feldman LS, Gan TJ, Kennedy RH, Ljungqvist O, Lobo DN, Miller T, Radtke FF, Ruiz Garces T, Schricker T, Scott MJ, Thacker JK, Ytrebø LM, Carli F (2016) Enhanced recovery after surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia practice. Acta Anaesthesiol Scand 60(3):289–334

    CAS  Article  Google Scholar 

  12. 12.

    Scott MJ, Baldini G, Fearon KC, Feldheiser A, Feldman LS, Gan TJ, Ljungqvist O, Lobo DN, Rockall TA, Schricker T, Carli F (2015) Enhanced recovery after surgery (ERAS) for gastrointestinal surgery, part 1: pathophysiological considerations. Acta Anaesthesiol Scand 59(10):1212–1231

    CAS  Article  Google Scholar 

  13. 13.

    Garfinkle R, Abou-Khalil J, Morin N, Ghitulescu G, Vasilevsky CA, Gordon P, Demian M, Boutros M (2017) Is there a role for oral antibiotic preparation alone before colorectal surgery? ACS-NSQIP analysis by coarsened exact matching. Dis Colon Rectum 60(7):729–737

    Article  Google Scholar 

  14. 14.

    Moffatt-Bruce SD, Hilligoss B, Gonsenhauser I (2017) ERAS: safety checklists, antibiotics, and VTE prophylaxis. J Surg Oncol 116(5):601–607

    Article  Google Scholar 

  15. 15.

    Jacquet P, Sugarbaker PH (1996) Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res 82:359–374

    CAS  Article  Google Scholar 

  16. 16.

    Sugarbaker PH (1998) Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis. Semin Surg Oncol 14(3):254–261

    CAS  Article  Google Scholar 

  17. 17.

    Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG (1992) CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol 13(10):606–608

    CAS  Article  Google Scholar 

  18. 18.

    Thursky K, Lingaratnam S, Jayarajan J, Haeusler GM, Teh B, Tew M, Venn G, Hiong A, Brown C, Leung V, Worth LJ, Dalziel K, Slavin MA (2018) Implementation of a whole of hospital sepsis clinical pathway in a cancer hospital: impact on sepsis management, outcomes and costs. BMJ Open Qual 7(3):e000355

    Article  Google Scholar 

  19. 19.

    Arslan NC, Sokmen S, Avkan-Oguz V, Obuz F, Canda AE, Terzi C et al (2017) Infectious complications after cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. Surg Infect 18(2):157–163

    Article  Google Scholar 

  20. 20.

    Baumgartner JM, Kwong TG, Ma GL, Messer K, Kelly KJ, Lowy AM (2016) A novel tool for predicting major complications after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 23(5):1609–1617

    Article  Google Scholar 

  21. 21.

    Canda AE, Sokmen S, Terzi C, Arslan C, Oztop I, Karabulut B, Ozzeybek D, Sarioglu S, Fuzun M (2013) Complications and toxicities after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 20(4):1082–1087

    Article  Google Scholar 

  22. 22.

    Capone A, Valle M, Proietti F, Federici O, Garofalo A, Petrosillo N (2007) Postoperative infections in cytoreductive surgery with hyperthermic intraperitoneal intraoperative chemotherapy for peritoneal carcinomatosis. J Surg Oncol 96(6):507–513

    CAS  Article  Google Scholar 

  23. 23.

    Dazza M, Schwarz L, Coget J, Frebourg N, Wood G, Huet E, Bridoux V, Veber B, Tuech JJ (2016) Does intraoperative systematic bacterial sampling during complete cytoreductive surgery (CRS) with hyperthermic intraoperative peritoneal chemotherapy (HIPEC) influence postoperative treatment? A new predictive factor for postoperative abdominal infectious complications. World J Surg 40(12):3035–3043

    Article  Google Scholar 

  24. 24.

    Baum ML, Anish DS, Chalmers TC, Sacks HS, Smith H Jr, Fagerstrom RM (1981) A survey of clinical trials of antibiotic prophylaxis in colon surgery: evidence against further use of no-treatment controls. N Engl J Med 305(14):795–799

    CAS  Article  Google Scholar 

  25. 25.

    Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M et al (2004) Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol : official journal of the American Society of Clinical Oncology 22(16):3284–3292

    CAS  Article  Google Scholar 

  26. 26.

    Murughan K, Tiwari M, Balakrishnan K (2014) Cytoreduction with hyperthermic intraperitoneal chemotherapy: an anaesthetic challenge. Indian J Anaesth 58(1):59–62

    Article  Google Scholar 

  27. 27.

    Wagner P, Boone B, Ramalingam L, Jones H, Zureikat A, Holtzman M et al (2015) Histologic and immunohistochemical alterations associated with cytoreductive surgery and heated intraperitoneal chemotherapy. Ann Surg Oncol 22(Suppl 3):S588–S595

    Article  Google Scholar 

  28. 28.

    Makrin V, Lev-Chelouche D, Even Sapir E, Paran H, Rabau M, Gutman M (2005) Intraperitoneal heated chemotherapy affects healing of experimental colonic anastomosis: an animal study. J Surg Oncol 89(1):18–22

    CAS  Article  Google Scholar 

  29. 29.

    Bozer M, Turkcapar N, Bayar S, Kocaoglu H (2005) Intraperitoneal hyperthermic perfusion may induce bacterial translocation. Hepato-gastroenterology. 52(61):111–114

    PubMed  Google Scholar 

  30. 30.

    Dumitra S, O'Leary M, Raoof M, Wakabayashi M, Dellinger TH, Han ES, et al. (2017) The comprehensive complication index: a new measure of the burden of complications after hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol

  31. 31.

    Fry DE (2016) Antimicrobial bowel preparation for elective colon surgery. Surg Infect 17(3):269–274

    Article  Google Scholar 

  32. 32.

    Calandra T, Marchetti O (2004) Clinical trials of antifungal prophylaxis among patients undergoing surgery. Clin Infect Dis : an official publication of the Infectious Diseases Society of America 39(Suppl 4):S185–S192

    CAS  Article  Google Scholar 

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Smibert, O.C., Slavin, M.A., Teh, B. et al. Epidemiology and risks for infection following cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. Support Care Cancer 28, 2745–2752 (2020). https://doi.org/10.1007/s00520-019-05093-5

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Keywords

  • CRS-HIPEC
  • Infection
  • Surgical site infection