Skip to main content

Advertisement

SpringerLink
Log in

Preoperative Liver Hypertrophy Induced by Portal Flow Occlusion Before Major Hepatic Resection for Colorectal Metastases Can Be Impaired by Bevacizumab

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

This prospective study evaluated the effect of bevacizumab on the hypertrophy of the future liver remnant (FLR) after portal vein occlusion (PVO) before major hepatectomy for colorectal liver metastases.

Methods

Twenty-seven patients with colorectal liver metastases treated with preoperative FOLFOX/FOLFIRI chemotherapy regimen since 2002 were evaluated for the degree of hypertrophy of the FLR after right PVO. The results were compared with a similar group of 13 patients treated since 2006 with a chemotherapeutic regimen including bevacizumab and PVO. The FLR was measured by volumetric computed tomography 4 weeks before and after PVO.

Results

Before PVO, the FLR volumes were similar in the 13 patients who received bevacizumab (bev+) (mean ± standard deviation, 497 ± 136 cm3) and the 27 patients who did not receive bevacizumab (bev−) (511 ± 222 cm3, P = NS). After PVO, the increase in the FLR volume was significantly lower in the bev+ group (561 ± 171 cm3) compared with the bev− group (667 ± 213 cm3, P < .031). In the bev+ group, patients who had received six or more cycles and were ≥60 years old experienced far lower hypertrophy. A right hepatectomy was performed in 29 patients (72%) without mortality and no clinically important differences in morbidity.

Conclusions

Bevacizumab may impair hypertrophy of the FLR after PVO in preparation for major hepatectomy particularly, in patients aged ≥60 years and those who receive six or more cycles of bevacizumab, suggesting that major liver resection should be considered with caution in patients who have received bevacizumab.

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
Fig. 3

Similar content being viewed by others

References

  1. Karoui M, Penna C, Amin-Hashem M, et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg. 2006;243:1–7.

    Article  PubMed  Google Scholar 

  2. Zorzi D, Laurent A, Pawlik TM, Lauwers GY, Vauthey JN, Abdalla EK. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg. 2007;94:274–86.

    Article  PubMed  CAS  Google Scholar 

  3. Ogata S, Belghiti J, Farges O, Varma D, Sibert A, Vilgrain V. Sequential arterial and portal vein embolization before right hepatectomy in patients with cirrhosis and hepatocellular carcinoma. Br J Surg. 2006;93:1091–8.

    Article  PubMed  CAS  Google Scholar 

  4. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucoverin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.

    Article  PubMed  CAS  Google Scholar 

  5. Saltz LB, Clarke S, Díaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26:2013–9.

    Article  PubMed  CAS  Google Scholar 

  6. Howdieshell TR, Callaway D, Webb WL, et al. Antibody neutralization of vascular endothelial growth factor inhibits wound granulation tissue formation. J Surg Res. 2001;96:173–82.

    Article  PubMed  CAS  Google Scholar 

  7. D’angelica M, Kornprat P, Gonen M, et al. Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched case-control study. Ann Surg Oncol. 2007;14:759–65.

    Article  PubMed  Google Scholar 

  8. Zorzi D, Chun YS, Madoff DC, Abdalla EK, Vauthey JN. Chemotherapy with bevacizumab does not affect liver regeneration after portal vein embolization in the treatment of colorectal liver metastases. Ann Surg Oncol. 2008;15:2765–72.

    Article  PubMed  Google Scholar 

  9. Reddy SK, Morse MA, Hurwitz HI, et al. Addition of bevacizumab to irinotecan- and oxaliplatin-based preoperative chemotherapy regimens does not increase morbidity after resection of colorectal liver metastases. J Am Coll Surg. 2008;206:96–106.

    Article  PubMed  Google Scholar 

  10. Van Buren G, Yang A, Dallas N, et al. The effect of molecular therapeutics on liver regeneration in a murine model. J Clin Oncol. 2008;26:1836–42.

    Article  PubMed  Google Scholar 

  11. Redaelli CA, Semela D, Carrick FE, et al. Effect of vascular endothelial growth factor on functional recovery after hepatectomy in lean and obese mice. J Hepatol. 2004;40:305–12.

    Article  PubMed  CAS  Google Scholar 

  12. Dokmak S, Aussilhou B, Faivre S, et al. Hépatectomie pour métastases hépatiques de cancer colorectal après chimiothérapie associée au bevacizumab: série unicentrique de 23 malades (abstract). J Chir. 2007;144.

  13. Farges O, Belghiti J, Kianmanesh R, et al. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg. 2003;237:208–17.

    Article  PubMed  Google Scholar 

  14. Balzan S, Belghiti J, Farges O, Sauvanet A. The “50–50 criteria” on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg. 2005;242:824–8.

    Article  PubMed  Google Scholar 

  15. Zhang F, Lei MP, Oswald TM, et al. The effect of vascular endothelial growth factor on the healing of ischemic skin wounds. Br J Plast Surg. 2003;56:334–41.

    Article  PubMed  CAS  Google Scholar 

  16. Giantonio BJ, Catalano PJ, Meropol NJ, et al. High-dose bevacizumab improves survival when combined with FOLFOX4 in previously treated advanced colorectal cancer: results from the Eastern Cooperative Oncology Group (ECOG) study E3200. J Clin Oncol. 2005;23:16s.

    Google Scholar 

  17. Roman CD, Choy H, Nanney L, et al. Vascular endothelial growth factor-mediated angiogenesis inhibition and postoperative wound healing in rats. J Surg Res. 2002;105:43–7.

    Article  PubMed  CAS  Google Scholar 

  18. LeCouter J, Moritz DR, Li B, et al. Angiogenesis-independant endothelial protection of liver: role of VEGFR-1. Science 2003;299:890–3.

    Article  PubMed  CAS  Google Scholar 

  19. Ribero D, Abdalla EK, Madoff DC, et al. Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome. Br J Surg. 2007;94:1386–94.

    Article  PubMed  CAS  Google Scholar 

  20. Di Stefano DR, de Baere T, Denys A, et al. Preoperative percutaneous portal vein embolization: evaluation of adverse events in 188 patients. Radiology 2005;234:625–30.

    Article  PubMed  Google Scholar 

  21. Aussilhou B, Lesurtel M, Sauvanet A, et al. Right portal vein ligation is as efficient as portal vein embolization to induce hypertrophy of the left liver remnant. J Gastrointest Surg. 2008;12:297–303.

    Article  PubMed  CAS  Google Scholar 

  22. Aloia T, Sebagh M, Plasse M, et al. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol. 2006;24:4983–90.

    Article  PubMed  CAS  Google Scholar 

  23. Ribero D, Wang H, Donadon M, et al. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer. 2007;110:2761–7.

    Article  PubMed  Google Scholar 

  24. Rubba-Brandt L, Giostra E, Brezault C, et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neoadjuvant chemotherapy followed by liver surgery. Ann Oncol. 2007;18:299–304.

    Article  Google Scholar 

  25. Gruenberger B, Tamandl D, Schueller J, et al. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol. 2008;26:1830–5.

    Article  PubMed  CAS  Google Scholar 

  26. Abdalla EK, Curley SA, Vauthey JN, et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg. 2004;239:818–27.

    Article  PubMed  Google Scholar 

  27. Bismuth H, Adam R, Levi F, et al. Resection of unresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg. 2000;66:611–5.

    Google Scholar 

  28. Adam R, Delvart V, Pasal G, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240:644–57.

    Article  PubMed  Google Scholar 

  29. Gagliano N, Grizzi F, Annoni G. Mechanisms of aging and liver functions. Dig Dis. 2007;25:118–23.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of HPB Surgery, Beaujon Hospital (Assistance Publique-Hôpitaux de Paris), University Paris 7, Clichy, France

    Béatrice Aussilhou MD, Safi Dokmak MD & Jacques Belghiti MD

  2. Department of Oncology, Beaujon Hospital (Assistance Publique-Hôpitaux de Paris), University Paris 7, Clichy, France

    Sandrine Faivre MD

  3. Department of Anatomopathology, Beaujon Hospital (Assistance Publique-Hôpitaux de Paris), University Paris 7, Clichy, France

    Valérie Paradis MD

  4. Department of Radiology, Beaujon Hospital (Assistance Publique-Hôpitaux de Paris), University Paris 7, Clichy, France

    Valérie Vilgrain MD

Authors
  1. Béatrice Aussilhou MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Safi Dokmak MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sandrine Faivre MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Valérie Paradis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Valérie Vilgrain MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jacques Belghiti MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jacques Belghiti MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aussilhou, B., Dokmak, S., Faivre, S. et al. Preoperative Liver Hypertrophy Induced by Portal Flow Occlusion Before Major Hepatic Resection for Colorectal Metastases Can Be Impaired by Bevacizumab. Ann Surg Oncol 16, 1553–1559 (2009). https://doi.org/10.1245/s10434-009-0447-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-009-0447-z

Keywords

Search

Navigation