Skip to main content
SpringerLink
Log in

Impact of preoperative chemotherapy on perioperative morbidity in combined resection of colon cancer and liver metastases

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Preoperative chemotherapy, or neoadjuvant therapy (NAC) can be used to improve resectability but can also have hepatotoxic effects on the future liver remnant. The purpose of this study was to investigate the impact of NAC on 30-day morbidity among patients undergoing a resection of primary colon cancer and synchronous liver metastases (sLM).

Methods

This was a retrospective study using the National Surgical Quality Improvement Program database (2012–2020). The association between NAC and 30-day overall morbidity, the primary outcome, was assessed. Subgroup analyses for low and high-risk procedures were performed.

Results

Among 968 patients who underwent the combined resection, 571 (58.99%) received NAC. There was a lower rate of 30-day overall morbidity among patients who received NAC (34.50% vs. 41.56%, p = 0.026) and no difference in rates of postoperative liver failure, bile leak, need for invasive intervention for hepatic procedure, and anastomotic leak. On adjusted analyses, patients who received NAC had decreased odds of overall morbidity (OR 0.73, 95% CI 0.55–0.97, p = 0.031) compared to patients who did not receive NAC. On subgroup analyses, patients who received NAC prior to a low risk combined resection had lower rates of overall morbidity on both adjusted and unadjusted analyses. Among those undergoing high-risk combined resections, there was no difference in overall morbidity.

Discussion and Conclusion

Patients who are deemed to be candidates for preoperative chemotherapy can proceed with planned neoadjuvant chemotherapy prior to combined resection of primary colon cancer and sLM as preoperative neoadjuvant chemotherapy does not appear to be associated with increased postoperative morbidity.

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

Similar content being viewed by others

References

  1. Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer Statistics, 2021. CA. Cancer J. Clin. 71, 7–33 (2021).

    Article  PubMed  Google Scholar 

  2. Hackl, C. et al. Treatment of colorectal liver metastases in Germany: a ten-year population-based analysis of 5772 cases of primary colorectal adenocarcinoma. BMC Cancer 14, 810 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Manfredi, S. et al. Epidemiology and management of liver metastases from colorectal cancer. Ann. Surg. 244, 254–259 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Coco, D. & Leanza, S. Analysis of Treatment Option for Synchronous Liver Metastases and Colon Rectal Cancer. Open Access Maced. J. Med. Sci. 7, 4176–4178 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Leporrier, J. et al. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br. J. Surg. 93, 465–474 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Behrenbruch, C. et al. Survival benefit of neoadjuvant chemotherapy and surgery versus surgery first for resectable colorectal liver metastases: a cohort study. ANZ J. Surg. 91, 1196–1202 (2021).

    Article  PubMed  Google Scholar 

  7. Khoo, E., O’Neill, S., Brown, E., Wigmore, S. J. & Harrison, E. M. Systematic review of systemic adjuvant, neoadjuvant and perioperative chemotherapy for resectable colorectal-liver metastases. HPB 18, 485–493 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hirokawa, F. et al. Neoadjuvant Chemotherapy Versus Upfront Surgery for Resectable Liver Metastases from Colorectal Cancer: a Multicenter, Propensity Score-Matched Cohort Study. J. Gastrointest. Surg. Off. J. Soc. Surg. Aliment. Tract 26, 772–781 (2022).

    Google Scholar 

  9. Khan, A. Z., Morris-Stiff, G. & Makuuchi, M. Patterns of chemotherapy-induced hepatic injury and their implications for patients undergoing liver resection for colorectal liver metastases. J. Hepatobiliary. Pancreat. Surg. 16, 137–144 (2009).

    Article  PubMed  Google Scholar 

  10. Wolf, P. S. et al. Preoperative chemotherapy and the risk of hepatotoxicity and morbidity after liver resection for metastatic colorectal cancer: a single institution experience. J. Am. Coll. Surg. 216, 41–49 (2013).

    Article  PubMed  Google Scholar 

  11. Makowiec, F. et al. Chemotherapy, liver injury, and postoperative complications in colorectal liver metastases. J. Gastrointest. Surg. Off. J. Soc. Surg. Aliment. Tract 15, 153–164 (2011).

    Article  Google Scholar 

  12. American College of Surgeons. About ACS-NSQIP. Accessed March 1, 2022. https://www.facs.org/quality-programs/acs-nsqip/about

  13. American College of Surgeons. ACS NSQIP Participant Use Data File. Accessed March 1, 2022. https://www.facs.org/quality-programs/acs-nsqip/participant-use

  14. Shubert, C. R. et al. A NSQIP Review of Major Morbidity and Mortality of Synchronous Liver Resection for Colorectal Metastasis Stratified by Extent of Liver Resection and Type of Colorectal Resection. J. Gastrointest. Surg. 19, 1982–1994 (2015).

    Article  PubMed  Google Scholar 

  15. Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205-213.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hosmer DW LS, Sturdivant RX. Applied Logistic Regression, 2nd ed. New York: Wiley, 2000.

    Book  Google Scholar 

  17. Margalit DN, Mamon HJ, Ancukiewicz M, Kobayashi W, Ryan DP, Blaszkowsky LS, Clark J, Willett CG, Hong TS. Tolerability of combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Int J Radiat Oncol Biol Phys. 2011 Dec 1;81(5):e735-41. https://doi.org/10.1016/j.ijrobp.2010.12.056. Epub 2011 Mar 4. PMID: 21377289.

    Article  PubMed  Google Scholar 

  18. Han MH, Park YY, Pratap S, Han YD, Cho MS, Hur H, Min BS, Lee KY, Kim NK. Short-term Outcomes After Upfront Chemotherapy Followed by Curative Surgery in Metastatic Colon Cancer: A Comparison With Upfront Surgery Patients. Ann Coloproctol. 2019 Dec;35(6):327-334. https://doi.org/10.3393/ac.2019.03.04.1. Epub 2019 Dec 31. PMID: 31937072; PMCID: PMC6968719.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Rubbia-Brandt L, Audard V, Sartoretti P, et al: Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 15::460,2004–46

  20. Tisman G, MacDonald D, Shindell N, et al: Oxaliplatin toxicity masquerading as recurrent colon cancer. J Clin Oncol 22::3202,2004–3204

  21. Zhu D, Zhong Y, Wei Y, Ye L, Lin Q, Ren L, Ye Q, Liu T, Xu J, Qin X. Effect of neoadjuvant chemotherapy in patients with resectable colorectal liver metastases. PLoS One. 2014 Jan 21;9(1):e86543. https://doi.org/10.1371/journal.pone.0086543. PMID: 24466143; PMCID: PMC3897724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Adam R, Bhangui P, Poston G, Mirza D, Nuzzo G, Barroso E, Ijzermans J, Hubert C, Ruers T, Capussotti L, Ouellet JF, Laurent C, Cugat E, Colombo PE, Milicevic M. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 252, 774–787 (2010).

  23. Makowiec F, Möhrle S, Neeff H, Drognitz O, Illerhaus G, Opitz OG, Hopt UT, zur Hausen A. Chemotherapy, liver injury, and postoperative complications in colorectal liver metastases. J Gastrointest Surg. 2011 Jan;15(1):153-64. https://doi.org/10.1007/s11605-010-1368-7

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the role of the Johns Hopkins Surgery Center for Outcomes Research (JSCOR) for supporting this study.

Funding

Sophia Y. Chen and Shannon R. Radomski received financial support from National Cancer Institute (NCI) Grant 5T32CA126607-12.

Mr. Edwin Lewis provided generous support of Dr. Efron's Department of Surgery Research Fund. The Nicholl Family Foundation provided generous support of the Johns Hopkins Division of Colorectal Surgery Research Fund.

Author information

Authors and Affiliations

  1. Colorectal Research Unit, Department of Surgery, Johns Hopkins University, Baltimore, USA

    Joy Z. Done, Angelos Papanikolaou, Miloslawa Stem, Shannon N. Radomski, Sophia Y. Chen, Chady Atallah, Jonathan E. Efron & Bashar Safar

  2. Division of Colon and Rectal Surgery, Department of Surgery, New York University Grossman School of Medicine, NYU Langone Health, 530 First Ave, Suite 7V, New York, NY, 10016, USA

    Bashar Safar

Authors
  1. Joy Z. Done
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angelos Papanikolaou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miloslawa Stem
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shannon N. Radomski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sophia Y. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chady Atallah
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jonathan E. Efron
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bashar Safar
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Concept and study design: JZD, AP, MS, SNR, SYC, CA, JEE, BS; Acquisition and analysis of data for the work: JZD, AP, MS, SNR; Drafting the work and revising critically for important intellectual content: all authors; final approval of the version to be published: all authors; agreement to be accountable for all aspects of the work in ensuring any questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors.

Corresponding author

Correspondence to Bashar Safar.

Ethics declarations

Ethical standards

This study was reviewed and approved by the Institutional Review Board of the Johns Hopkins University School of Medicine.

Conflicts of interest

None declared.

Additional information

Publisher's note

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

Supplementary information

ESM 1

(DOCX 18.1 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Done, J.Z., Papanikolaou, A., Stem, M. et al. Impact of preoperative chemotherapy on perioperative morbidity in combined resection of colon cancer and liver metastases. J Gastrointest Surg 27, 2380–2387 (2023). https://doi.org/10.1007/s11605-023-05758-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-023-05758-x

Keywords

Search

Navigation