Skip to main content

Advertisement

SpringerLink
Log in

Chemotherapy, Liver Injury, and Postoperative Complications in Colorectal Liver Metastases

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

Abstract

Background

Systemic chemotherapy (CTx) is increasingly used before surgery for colorectal liver metastases (CRC-LM). However, CTx may cause liver injury like steatosis, steatohepatitis, and sinusoidal injury which may be associated with postoperative morbidity. Some recent data have even shown an increased mortality in patients with CTx-associated steatohepatitis. We, therefore, analyzed our recent experience with potential hepatic injury and its association with CTx and morbidity in patients undergoing surgery for CRC-LM.

Methods

From 2001 to 2007, 179 patients underwent primary liver resection for CRC-LM. Sufficient non-tumorous liver parenchyma could be re-evaluated for this study in 102 patients. In these 102 patients (66% male, median age 62 years, median BMI 26, 8% diabetics (IDDM)), liver injury was classified using established criteria for steatosis and sinusoidal dilatation (SD) and then compared with preoperative CTx and postoperative outcome. Fifty-eight percent of the operations were (extended) hemihepatectomies (ExtRes), 42% segmental or wedge resections (LimRes). Before resection, 66% had received CTx (33% FU-based (FU), 19% oxaliplatin-based (Oxa), 12% irinotecan-based (Iri), and 3% Oxa+Iri). The interval between CTx and surgery was always ≥4 weeks.

Results

Mortality was 3/102 (2.9%). Any complication occurred in 48%, hepatic insufficiency in 5.9%, and liver-related complications in 24%. Hepatic steatosis >20% was found in 37% (half of them with steatosis >50%). BMI correlated with the frequency of steatosis. Steatosis >20% was more frequent in patients with preoperative chemotherapy but did not depend on the chemotherapy regimen. No relevant risk factor for grades 2 and 3 SD was found. The specific use of Oxa or Iri did not significantly correlate with hepatic injury. Neither a CTx per se nor the different CTx regimens nor the extent of hepatic injury showed any negative influence on mortality, complication rates, or hepatic insufficiency. Patients with IDDM had a higher mortality (25% vs 1% without IDDM; p < 0.02), increased complication rate (75% vs 46%; p = 0.11), a higher rate of hepatic insufficiency (25% vs 4%; p < 0.02), and more liver related complications (50% vs 21%; p = 0.06). Patients undergoing ExtRes had a higher overall (p < 0.01) and liver-related (p = 0.05) complication rate compared to LimRes. None of the 34 patients with preoperative Oxa or Iri died or developed hepatic insufficiency.

Conclusions

In our experience, hepatic injury (steatosis) was influenced by BMI and by preoperative CTx. Neither preoperative CTx nor liver injury increased perioperative morbidity. Patients with IDDM were at a rather high perioperative risk.

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
Fig. 2

Similar content being viewed by others

References

  1. Pawlik TM, Scoggins CR, Zorzi D, Abdalla EK, Andres A, Eng C, Curley SA, Loyer EM, Muratore A, Mentha G, Capussotti L, Vauthey JN. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg 2005;241:715–722, discussion.

    Article  PubMed  Google Scholar 

  2. Abdalla EK, Vauthey JN, Ellis LM, Ellis V, Pollock R, Broglio KR, Hess K, Curley SA. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 2004;239:818–825.

    Article  PubMed  Google Scholar 

  3. Oussoultzoglou E, Rosso E, Fuchshuber P, Stefanescu V, Diop B, Giraudo G, Pessaux P, Bachellier P, Jaeck D. Perioperative carcinoembryonic antigen measurements to predict curability after liver resection for colorectal metastases: a prospective study. Arch Surg 2008;143:1150–1158.

    Article  PubMed  Google Scholar 

  4. Fernandez FG, Drebin JA, Linehan DC, Dehdashti F, Siegel BA, Strasberg SM. Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET). Ann Surg 2004;240:438–447.

    Article  PubMed  Google Scholar 

  5. de Haas RJ, Wicherts DA, Flores E, Azoulay D, Castaing D, Adam R. R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg 2008;248:626–637.

    PubMed  Google Scholar 

  6. Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343–2351.

    Article  PubMed  CAS  Google Scholar 

  7. Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crino L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 2007;25:1670–1676.

    Article  PubMed  CAS  Google Scholar 

  8. Bismuth H, Adam R, Levi F, Farabos C, Waechter F, Castaing D, Majno P, Engerran L. Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg 1996;224:509–520.

    Article  PubMed  CAS  Google Scholar 

  9. Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, Giacchetti S, Paule B, Kunstlinger F, Ghemard O, Levi F, Bismuth H. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 2004;240:644–657.

    Article  PubMed  Google Scholar 

  10. Adam R, Wicherts DA, de Haas RJ, Ciacio O, Levi F, Paule B, Ducreux M, Azoulay D, Bismuth H, Castaing D. Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? J Clin Oncol 2009;27:1829–1835.

    Article  PubMed  Google Scholar 

  11. Masi G, Loupakis F, Pollina L, Vasile E, Cupini S, Ricci S, Brunetti IM, Ferraldeschi R, Naso G, Filipponi F, Pietrabissa A, Goletti O, Baldi G, Fornaro L, Andreuccetti M, Falcone A. Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) followed by radical surgery of metastases. Ann Surg 2009;249:420–425.

    Article  PubMed  Google Scholar 

  12. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van CE, Scheithauer W, Gruenberger T. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 2008;371:1007–1016.

    Article  PubMed  CAS  Google Scholar 

  13. Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le CM, Dousset B, Morel P, Soubrane O, Chaussade S, Mentha G, Terris B. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 2004;15:460–466.

    Article  PubMed  CAS  Google Scholar 

  14. Vauthey JN, Pawlik TM, Ribero D, Wu TT, Zorzi D, Hoff PM, Xiong HQ, Eng C, Lauwers GY, Mino-Kenudson M, Risio M, Muratore A, Capussotti L, Curley SA, Abdalla EK. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 2006;24:2065–2072.

    Article  PubMed  CAS  Google Scholar 

  15. Pawlik TM, Olino K, Gleisner AL, Torbenson M, Schulick R, Choti MA. Preoperative chemotherapy for colorectal liver metastases: impact on hepatic histology and postoperative outcome. J Gastrointest Surg 2007;11:860–868.

    Article  PubMed  Google Scholar 

  16. Chun YS, Laurent A, Maru D, Vauthey JN. Management of chemotherapy-associated hepatotoxicity in colorectal liver metastases. Lancet Oncol 2009;10:278–286.

    Article  PubMed  CAS  Google Scholar 

  17. Kooby DA, Fong Y, Suriawinata A, Gonen M, Allen PJ, Klimstra DS, Dematteo RP, D’Angelica M, Blumgart LH, Jarnagin WR. Impact of steatosis on perioperative outcome following hepatic resection. J Gastrointest Surg 2003;7:1034–1044.

    Article  PubMed  Google Scholar 

  18. Nakano H, Oussoultzoglou E, Rosso E, Casnedi S, Chenard-Neu MP, Dufour P, Bachellier P, Jaeck D. Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Ann Surg 2008;247:118–124.

    Article  PubMed  Google Scholar 

  19. Karoui M, Penna C, min-Hashem M, Mitry E, Benoist S, Franc B, Rougier P, Nordlinger B. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg 2006;243:1–7.

    Article  PubMed  Google Scholar 

  20. Fernandez FG, Ritter J, Goodwin JW, Linehan DC, Hawkins WG, Strasberg SM. Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases. J Am Coll Surg 2005;200:845–853.

    Article  PubMed  Google Scholar 

  21. Kleiner DE, Brunt EM, Van NM, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–1321.

    Article  PubMed  Google Scholar 

  22. Aloia T, Sebagh M, Plasse M, Karam V, Levi F, Giacchetti S, Azoulay D, Bismuth H, Castaing D, Adam R. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol 2006;24:4983–4990.

    Article  PubMed  CAS  Google Scholar 

  23. Brouquet A, Benoist S, Julie C, Penna C, Beauchet A, Rougier P, Nordlinger B. Risk factors for chemotherapy-associated liver injuries: A multivariate analysis of a group of 146 patients with colorectal metastases. Surgery 2009;145:362–371.

    Article  PubMed  Google Scholar 

  24. Jarnagin WR, Gonen M, Fong Y, Dematteo RP, Ben-Porat L, Little S, Corvera C, Weber S, Blumgart LH. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg 2002;236:397–406.

    Article  PubMed  Google Scholar 

  25. Belghiti J, Hiramatsu K, Benoist S, Massault P, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the 1990 s: an update to evaluate the actual risk of liver resection. J Am Coll Surg 2000;191:38–46.

    Article  PubMed  CAS  Google Scholar 

  26. Behrns KE, Tsiotos GG, DeSouza NF, Krishna MK, Ludwig J, Nagorney DM. Hepatic steatosis as a potential risk factor for major hepatic resection. J Gastrointest Surg 1998;2:292–298.

    Article  PubMed  CAS  Google Scholar 

  27. Mullen JT, Ribero D, Reddy SK, Donadon M, Zorzi D, Gautam S, Abdalla EK, Curley SA, Capussotti L, Clary BM, Vauthey JN. Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy. J Am Coll Surg 2007;204:854–862.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany

    Frank Makowiec, Simone Möhrle, Hannes Neeff, Oliver Drognitz & Ulrich T. Hopt

  2. Department of Haematology and Oncology, University of Freiburg, Freiburg, Germany

    Gerald Illerhaus

  3. Comprehensive Cancer Center, University of Freiburg, Freiburg, Germany

    Oliver G. Opitz

  4. Institute of Pathology, University of Freiburg, Freiburg, Germany

    Axel zur Hausen

Authors
  1. Frank Makowiec
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simone Möhrle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hannes Neeff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Oliver Drognitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gerald Illerhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Oliver G. Opitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ulrich T. Hopt
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Axel zur Hausen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frank Makowiec.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Makowiec, F., Möhrle, S., Neeff, H. et al. Chemotherapy, Liver Injury, and Postoperative Complications in Colorectal Liver Metastases. J Gastrointest Surg 15, 153–164 (2011). https://doi.org/10.1007/s11605-010-1368-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-010-1368-7

Keywords

Search

Navigation