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01.03.2012 | Original Article

Impact of Biomarkers Expression Before and After Portal Vein Embolization on Recurrence After Two-Stage Hepatectomy for Colorectal Liver Metastases

verfasst von: Masato Narita, Elie Oussoultzoglou, Marie-Pierre Chenard, Pascal Fuchshuber, Edoardo Rosso, Patrick Pessaux, Daniel Jaeck, Philippe Bachellier

Erschienen in: Journal of Gastrointestinal Surgery | Ausgabe 3/2012

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Abstract

Background

The adverse oncological effect of portal vein embolization (PVE) in patients with colorectal liver metastases (CLM) remains controversial. This study was designed to evaluate the effect of PVE on change of tumor characteristics using tumor specimens obtained from sequential hepatectomy before and after PVE.

Methods

Between December 1996 and April 2009, among 55 patients who achieved two-stage hepatectomy (TSH) combined with PVE, 39 had available cancer tissue blocks from both the first- and second-stage hepatectomy and constituted the study population. The immunohistochemistry of Ki67 and Bcl-2 before and after PVE was performed. Biomarker expressions and clinicopathological variables were assessed and their impact on recurrence was analyzed.

Results

Whereas tumor volume and carcinoembryonic serum level significantly increased after PVE, the expression of Ki67 and Bcl-2 remained similar before and after PVE. The Bcl-2 ratio (expressed as Bcl-2 after PVE over Bcl-2 before PVE) was an independent prognostic factor for recurrence-free survival (P = 0.030). Patients with Bcl-2 ratio ≤1 had a significantly longer median recurrence-free survival compared with those with Bcl-2 ratio >1 receiving or not receiving adjuvant chemotherapy (24.8 months versus 8.9 or 5.8 months, respectively).

Conclusion

Bcl-2 ratio may predict early recurrence and identify patients who do not require postoperative chemotherapy in patients undergoing TSH with PVE for CLM.

Jaeck D, Oussoultzoglou E, Rosso E, Greget M, Weber JC, Bachellier P. A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg 2004;240:1037–49; discussion 1049–51.PubMedCrossRef

Narita M, Oussoultzoglou E, Jaeck D, Fuchschuber P, Rosso E, Pessaux P, et al. Two-stage hepatectomy for multiple bilobar colorectal liver metastases. Br J Surg. 2011; 98:1463–1475. doi:10.1002/bjs.7580.PubMedCrossRef

Narita M, Oussoultzoglou E, Bachellier P, Rosso E, Pessaux P, Jaeck D. Two-stage hepatectomy procedure to treat initially unresectable multiple bilobar colorectal liver metastases: technical aspects. Dig Surg2011;28:121–6.PubMedCrossRef

Folprecht G, Grothey A, Alberts S, Raab HR, Kohne CH. Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol 2005;16:1311–9.PubMedCrossRef

Wicherts DA, Miller R, de Haas RJ, Bitsakou G, Vibert E, Veilhan LA, et al. Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg 2008;248:994–1005.PubMedCrossRef

Makuuchi M, Thai BL, Takayasu K, Takayama T, Kosuge T, Gunven P, et al. Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery 1990;107:521–7.PubMed

de Graaf W, van den Esschert JW, van Lienden KP, van Gulik TM. Induction of tumor growth after preoperative portal vein embolization: is it a real problem? Ann Surg Oncol 2009;16:423–30.PubMedCrossRef

Elias D, De Baere T, Roche A, Mducreux, Leclere J, Lasser P. During liver regeneration following right portal embolization the growth rate of liver metastases is more rapid than that of the liver parenchyma. Br J Surg 1999;86:784–8.PubMedCrossRef

Pamecha V, Levene A, Grillo F, Woodward N, Dhillon A, Davidson BR. Effect of portal vein embolisation on the growth rate of colorectal liver metastases. Br J Cancer 2009;100:617–22.PubMedCrossRef

10.

Hayashi S, Baba Y, Ueno K, Nakajo M, Kubo F, Ueno S, et al. Acceleration of primary liver tumor growth rate in embolized hepatic lobe after portal vein embolization. Acta Radiol 2007;48:721–7.PubMedCrossRef

11.

Barbaro B, Di Stasi C, Nuzzo G, Vellone M, Giuliante F, Marano P. Preoperative right portal vein embolization in patients with metastatic liver disease. Metastatic liver volumes after RPVE. Acta Radiol 2003;44:98–102.PubMedCrossRef

12.

Kokudo N, Tada K, Seki M, Ohta H, Azekura K, Ueno M, et al. Proliferative activity of intrahepatic colorectal metastases after preoperative hemihepatic portal vein embolization. Hepatology 2001;34:267–72.PubMedCrossRef

13.

Oussoultzoglou E, Bachellier P, Rosso E, Scurtu R, Lucescu I, Greget M, et al. Right portal vein embolization before right hepatectomy for unilobar colorectal liver metastases reduces the intrahepatic recurrence rate. Ann Surg 2006;244:71–9.PubMedCrossRef

14.

Giraudo G, Greget M, Oussoultzoglou E, Rosso E, Bachellier P, Jaeck D. Preoperative contralateral portal vein embolization before major hepatic resection is a safe and efficient procedure: a large single institution experience. Surgery 2008;143:476–82.PubMedCrossRef

15.

Zeitlin BD, Zeitlin IJ, Nor JE. Expanding circle of inhibition: small-molecule inhibitors of Bcl-2 as anticancer cell and antiangiogenic agents. J Clin Oncol 2008;26:4180–8.PubMedCrossRef

16.

Oussoultzoglou E, Rosso E, Fuchshuber P, Stefanescu V, Diop B, Giraudo G, et al. Perioperative carcinoembryonic antigen measurements to predict curability after liver resection for colorectal metastases: a prospective study. Arch Surg 2008;143:1150–8; discussion 1158–9.PubMedCrossRef

17.

Urruticoechea A, Smith IE, Dowsett M. Proliferation marker Ki-67 in early breast cancer. J Clin Oncol 2005;23:7212–20.PubMedCrossRef

18.

Rosenau J, Bahr MJ, von Wasielewski R, Mengel M, Schmidt HH, Nashan B, et al. Ki67, E-cadherin, and p53 as prognostic indicators of long-term outcome after liver transplantation for metastatic neuroendocrine tumors. Transplantation 2002;73:386–94.PubMedCrossRef

19.

Trere D, Montanaro L, Ceccarelli C, Barbieri S, Cavrini G, Santini D, et al. Prognostic relevance of a novel semiquantitative classification of Bcl2 immunohistochemical expression in human infiltrating ductal carcinomas of the breast. Ann Oncol 2007;18:1004–14.PubMedCrossRef

20.

Budwit-Novotny DA, McCarty KS, Cox EB, Soper JT, Mutch DG, Creasman WT, et al. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res 1986;46:5419–25.PubMed

21.

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–16.PubMedCrossRef

22.

Kito Y, Nagino M, Nimura Y. Doppler sonography of hepatic arterial blood flow velocity after percutaneous transhepatic portal vein embolization. AJR Am J Roentgenol 2001;176:909–12.PubMed

23.

Kollmar O, Corsten M, Scheuer C, Vollmar B, Schilling MK, Menger MD. Portal branch ligation induces a hepatic arterial buffer response, microvascular remodeling, normoxygenation, and cell proliferation in portal blood-deprived liver tissue. Am J Physiol Gastrointest Liver Physiol 2007;292:G1534–42.PubMedCrossRef

24.

Starkel P, Horsmans Y, Sempoux C, De Saeger C, Wary J, Lause P, et al. After portal branch ligation in rat, nuclear factor kappaB, interleukin-6, signal transducers and activators of transcription 3, c-fos, c-myc, and c-jun are similarly induced in the ligated and nonligated lobes. Hepatology 1999;29:1463–70.PubMedCrossRef

25.

Uemura T, Miyazaki M, Hirai R, Matsumoto H, Ota T, Ohashi R, et al. Different expression of positive and negative regulators of hepatocyte growth in growing and shrinking hepatic lobes after portal vein branch ligation in rats. Int J Mol Med 2000;5:173–9.PubMed

26.

Picard C, Starkel P, Sempoux C, Saliez A, Lebrun V, Horsmans Y. Molecular mechanisms of apoptosis in the liver of rats after portal branch ligation with and without retrorsine. Lab Invest 2004;84:618–28.PubMedCrossRef

27.

Saegusa M, Takano Y, Okayasu I. Bcl-2 expression and its association with cell kinetics in human gastric carcinomas and intestinal metaplasia. J Cancer Res Clin Oncol 1995;121:357–63.PubMedCrossRef

28.

Saleh HA, Jackson H, Banerjee M. Immunohistochemical expression of bcl-2 and p53 oncoproteins: correlation with Ki67 proliferation index and prognostic histopathologic parameters in colorectal neoplasia. Appl Immunohistochem Mol Morphol 2000;8:175–82.PubMedCrossRef

29.

Gorczyca W, Markiewski M, Kram A, Tuziak T, Domagala W. Immunohistochemical analysis of bcl-2 and p53 expression in breast carcinomas: their correlation with Ki-67 growth fraction. Virchows Arch 1995;426:229–33.PubMedCrossRef

30.

Vincent-Salomon A, Rousseau A, Jouve M, Beuzeboc P, Sigal-Zafrani B, Freneaux P, et al. Proliferation markers predictive of the pathological response and disease outcome of patients with breast carcinomas treated by anthracycline-based preoperative chemotherapy. Eur J Cancer 2004;40:1502–8.PubMedCrossRef

31.

Penault-Llorca F, Andre F, Sagan C, Lacroix-Triki M, Denoux Y, Verriele V, et al. Ki67 expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol 2009;27:2809–15.PubMedCrossRef

32.

Meads MB, Gatenby RA, Dalton WS. Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev Cancer 2009;9:665–74.PubMedCrossRef

33.

Wilson C, Purcell C, Seaton A, Oladipo O, Maxwell PJ, O'Sullivan JM, et al. Chemotherapy-induced CXC-chemokine/CXC-chemokine receptor signaling in metastatic prostate cancer cells confers resistance to oxaliplatin through potentiation of nuclear factor-kappaB transcription and evasion of apoptosis. J Pharmacol Exp Ther 2008;327:746–59.PubMedCrossRef

34.

Fisher TC, Milner AE, Gregory CD, Jackman AL, Aherne GW, Hartley JA, et al. Bcl-2 modulation of apoptosis induced by anticancer drugs: resistance to thymidylate stress is independent of classical resistance pathways. Cancer Res 1993;53:3321–6.PubMed

35.

Bedikian AY, Millward M, Pehamberger H, Conry R, Gore M, Trefzer U, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol 2006;24:4738–45.PubMedCrossRef

36.

Tolcher AW, Chi K, Kuhn J, Gleave M, Patnaik A, Takimoto C, et al. A phase II, pharmacokinetic, and biological correlative study of oblimersen sodium and docetaxel in patients with hormone-refractory prostate cancer. Clin Cancer Res 2005;11:3854–61.PubMedCrossRef

37.

Mita MM, Ochoa L, Rowinsky EK, Kuhn J, Schwartz G, Hammond LA, et al. A phase I, pharmacokinetic and biologic correlative study of oblimersen sodium (Genasense, G3139) and irinotecan in patients with metastatic colorectal cancer. Ann Oncol 2006;17:313–21.PubMedCrossRef

38.

Chan JK. Advances in immunohistochemistry: impact on surgical pathology practice. Semin Diagn Pathol 2000;17:170–7.PubMed

Titel: Impact of Biomarkers Expression Before and After Portal Vein Embolization on Recurrence After Two-Stage Hepatectomy for Colorectal Liver Metastases
verfasst von: Masato Narita
Elie Oussoultzoglou
Marie-Pierre Chenard
Pascal Fuchshuber
Edoardo Rosso
Patrick Pessaux
Daniel Jaeck
Philippe Bachellier
Publikationsdatum: 01.03.2012
Verlag: Springer-Verlag
Erschienen in: Journal of Gastrointestinal Surgery / Ausgabe 3/2012
Print ISSN: 1091-255X
Elektronische ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-011-1732-2

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Abstract

Background

Methods

Results

Conclusion

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