Skip to main content
Top
Published in: Annals of Surgical Oncology 6/2009

01-06-2009 | Gastrointestinal Oncology

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

Authors: Béatrice Aussilhou, MD, Safi Dokmak, MD, Sandrine Faivre, MD, Valérie Paradis, MD, Valérie Vilgrain, MD, Jacques Belghiti, MD

Published in: Annals of Surgical Oncology | Issue 6/2009

Login to get access

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.
Literature
1.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
2.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
5.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
6.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
7.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
12.
go back to reference 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. 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.
go back to reference Farges O, Belghiti J, Kianmanesh R, et al. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg. 2003;237:208–17.PubMedCrossRef Farges O, Belghiti J, Kianmanesh R, et al. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg. 2003;237:208–17.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference 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. 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.
17.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference LeCouter J, Moritz DR, Li B, et al. Angiogenesis-independant endothelial protection of liver: role of VEGFR-1. Science 2003;299:890–3.PubMedCrossRef LeCouter J, Moritz DR, Li B, et al. Angiogenesis-independant endothelial protection of liver: role of VEGFR-1. Science 2003;299:890–3.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference 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.CrossRef 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.CrossRef
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
27.
go back to reference 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. 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.
28.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
29.
go back to reference Gagliano N, Grizzi F, Annoni G. Mechanisms of aging and liver functions. Dig Dis. 2007;25:118–23.PubMedCrossRef Gagliano N, Grizzi F, Annoni G. Mechanisms of aging and liver functions. Dig Dis. 2007;25:118–23.PubMedCrossRef
Metadata
Title
Preoperative Liver Hypertrophy Induced by Portal Flow Occlusion Before Major Hepatic Resection for Colorectal Metastases Can Be Impaired by Bevacizumab
Authors
Béatrice Aussilhou, MD
Safi Dokmak, MD
Sandrine Faivre, MD
Valérie Paradis, MD
Valérie Vilgrain, MD
Jacques Belghiti, MD
Publication date
01-06-2009
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 6/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0447-z

Other articles of this Issue 6/2009

Annals of Surgical Oncology 6/2009 Go to the issue