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Influence of Chemotherapy on Liver Regeneration Induced by Portal Vein Embolization or First Hepatectomy of a Staged Procedure for Colorectal Liver Metastases

  • Original Article
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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Although portal vein embolization (PVE) and staged hepatectomy (StHx), as well as prehepatectomy chemotherapy, have improved the resectability rate of patients with multiple bilobar colorectal liver metastases, the impact of prehepatectomy chemotherapy on liver hypertrophy following PVE and/or StHx has remained unclear.

Methods

Sixty patients who underwent PVE followed by one-stage hepatectomy and StHx with or without PVE were analyzed. Liver hypertrophy following PVE and/or the first hepatectomy of StHx and the clinical course after final hepatectomy was compared between patients with and without prehepatectomy chemotherapy.

Results

No difference of volume of the future liver remnant (FLR) before or after the procedure was seen between the chemotherapy group and the nonchemotherapy group. Even in 38 patients who underwent right PVE prior to a planned right hemihepatectomy, the chemotherapy group (n = 14) and the nonchemotherapy group (n = 24) were comparable in terms of volumes of FLR before (P = 0.71) and after (P = 0.29) PVE and posthepatectomy courses. However, the liver hypertrophy ratio for patients showing steatosis in adjacent nonmalignant liver parenchyma, which frequently is induced by chemotherapy, was lower than that for patients without steatosis (P = 0.04).

Conclusions

Although prehepatectomy chemotherapy did not impair liver hypertrophy, PVE and/or StHx accompanied by prehepatectomy chemotherapy should be performed with particular care to minimize risk of liver failure after the procedure.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CA:

Carbohydrate antigen

CDDP:

Cisplatin

CEA:

Carcinoembryonic antigen

CT:

Computed tomography

FA:

l-Folinic acid

FLR:

Future liver remnant

5-FU:

5-Fluorouracil

PET:

Positron emission tomography

PLT:

Platelet count

PS:

Prediction score

PT-INR:

Prothrombin time as the international normalized ratio

PVE:

Portal vein embolization

StHx:

2-Stage hepatectomy

TB:

Total bilirubin

References

  1. Abdalla EK, Hicks ME, Vauthey JN. Portal vein embolization: rationale, technique and future prospects. Br J Surg 2001;88:165–175.

    Article  CAS  PubMed  Google Scholar 

  2. Azoulay D, Castaing D, Smail A, Adam R, Cailliez V, Laurent A, Lemoine A, Bismuth H. Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization. Ann Surg 2000;231:480–486.

    Article  CAS  PubMed  Google Scholar 

  3. Adam R, Laurent A, Azoulay D, Castaing D, Bismuth H. Two-stage hepatectomy: a planned strategy to treat irresectable liver tumors. Ann Surg 2000;232:777–785.

    Article  CAS  PubMed  Google Scholar 

  4. Kianmanesh R, Farges O, Abdalla EK, Sauvanet A, Ruszniewski P, Belghiti J. Right portal vein ligation: a new planned two-step all-surgical approach for complete resection of primary gastrointestinal tumors with multiple bilateral liver metastases. J Am Coll Surg 2003;197:164–170.

    Article  PubMed  Google Scholar 

  5. 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: 37–51.

    Article  Google Scholar 

  6. Elias D, De Baere T, Roche A, Ducreux M, 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;86:784–788.

    Article  CAS  PubMed  Google Scholar 

  7. Kokudo N, Tada K, Seki M, Ohta H, Azekura K, Ueno M, Ohta K, Yamaguchi T, Matsubara T, Takahashi T, Nakajima T, Muto T, Ikari T, Yanagisawa A, Kato Y. Proliferative activity of intrahepatic colorectal metastases after preoperative hemihepatic portal vein embolization. Hepatology 2001;34:267–272.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. Yamanaka N, Okamoto E, Oriyama T, Fujimoto J, Furukawa K, Kawamura E, Tanaka T, Tomoda F. A prediction scoring system to select the surgical treatment of liver cancer. Further refinement based on 10 years of use. Ann Surg 1994;219:342–346.

    Article  CAS  PubMed  Google Scholar 

  10. The Brisbane 2000 Terminology of Liver Anatomy and Resection A. Terminology Committee of the International Hepato-Pancreato-Biliary Association. HPB 2000;2:333–339.

    Google Scholar 

  11. Lévi F, Zidani R, Misset JL. Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet 1997;350:681–686.

    Article  PubMed  Google Scholar 

  12. Abdalla EK, Hicks ME, Vauthey JN. Portal vein embolization: rationale, technique and future prospects. Br J Surg 2001;88:165–753.

    Article  CAS  PubMed  Google Scholar 

  13. Farges O, Belghiti J, Kianmanesh R, Regimbeau JM, Santoro R, Vilgrain V, Denys A, Sauvanet A. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg 2003;237:208–217.

    Article  PubMed  Google Scholar 

  14. Jaeck D, Bachellier P, Nakano H, Oussoultzoglou E, Weber JC, Wolf P, Greget M. One or two-stage hepatectomy combined with portal vein embolization for initially nonresectable colorectal liver metastases. Am J Surg 2003;185:221–229.

    Article  PubMed  Google Scholar 

  15. Ko GY, Sung KB, Yoon HK, Kim JH, Weon YC, Song HY. Preoperative portal vein embolization with a new liquid embolic agent. Radiology 2003;227:407–413.

    Article  PubMed  Google Scholar 

  16. Tanaka K, Shimada H, Matsuo K, Ueda M, Endo I, Togo S. Two-stage hepatectomy in treatment of multiple bilobar colorectal metastases: remnant liver regeneration compared with portal vein embolization preceding one-stage hepatectomy. Eur J Surg Oncol 2007;33:329–335.

    Article  CAS  PubMed  Google Scholar 

  17. Yamanaka N, Okamoto E, Kawamura E, Kato T, Oriyama T, Fujimoto J, Furukawa K, Tanaka T, Tomoda F, Tanaka W. Dynamics of normal and injured human liver regeneration after hepatectomy as assessed on the basis of computed tomography and liver function. Hepatology 1993;18:79–85.

    Article  CAS  PubMed  Google Scholar 

  18. Tani M, Tomiya T, Yamada S, Hayashi S, Yahata K, Tamura Y, Akiyama M, Kawai S, Masaki N, Fujiwara K. Regulating factors of liver regeneration after hepatectomy. Cancer Chemother Pharmacol 1994;33(Suppl):29–32.

    Article  Google Scholar 

  19. Ogasawara K, Une Y, Nakajima Y, Uchino J. The significance of measuring liver volume using computed tomographic images before and after hepatectomy. Surg Today 1995;25:43–48.

    Article  CAS  PubMed  Google Scholar 

  20. Tanaka W, Yamanaka N, Oriyama T, Katoh T, Kuroda N, Okamoto E. Multivariate analysis of liver regenerative capacity after hepatectomy in humans. J Hepatobiliary Pancreat Surg 1997;4:78–82.

    Article  Google Scholar 

  21. Shimada M, Matsumata T, Maeda T, Itasaka H, Suehiro T, Sugimachi K. Hepatic regeneration following right lobectomy: estimation of regenerative capacity. Surg Today 1994;24:44–48.

    Article  CAS  PubMed  Google Scholar 

  22. Fisher B, Szuch P, Levine M, Fisher ER. A portal blood factor as the humoral agent in liver regeneration. Science 1971;171:575–577.

    Article  CAS  PubMed  Google Scholar 

  23. Starzl TE, Porter KA, Kashiwagi N. Portal hepatotrophic factors, diabetes mellitus and acute liver atrophy, hypertrophy and regeneration. Surg Gynecol Obstet. 1975;141:843–858.

    CAS  PubMed  Google Scholar 

  24. Peppercorn PD, Reznek RH, Wilson P, Slevin ML, Gupta RK. Demonstration of hepatic steatosis by computerized tomography in patients receiving 5-fluorouracil-based therapy for advanced colorectal cancer. Br J Cancer 1998;77:2008–2011.

    CAS  PubMed  Google Scholar 

  25. 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  CAS  PubMed  Google Scholar 

  26. Aloia T, Sebagh M, Plasse M, Karam V, Lévi 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  CAS  PubMed  Google Scholar 

  27. Di Stefano G, Derenzini M, Kratz F, Lanza M, Fiume L. Liver-targeted doxorubicin: effects on rat regenerating hepatocytes. Liver Int 2004;24:246–252.

    Article  PubMed  Google Scholar 

  28. Herrera MC, Palomero MF, Macias RI, Serrano MA, Marin JJ. Comparison of the effects of bischolylglycinatechloro-platinum(II) versus cisplatin on liver regeneration after partial hepatectomy. Anticancer Res 1998;18:3555–3563.

    CAS  PubMed  Google Scholar 

  29. Goere D, Farges O, Leporrier J, Sauvanet A, Vilgrain V, Belghiti J. Chemotherapy does not impair hypertrophy of the left liver after right portal vein obstruction. J Gastrointest Surg 2006;10:365–370.

    Article  PubMed  Google Scholar 

  30. Nagasue N, Kobayashi M, Iwaki A, Yukaya H, Kanashima R, Inokughi K. Effect of 5-fluorouracil on liver regeneration and metabolism after partial hepatectomy in the rat. Cancer 1978;41:435–443.

    Article  CAS  PubMed  Google Scholar 

  31. Ezaki T, Koyanagi N, Toyomasu T, Ikeda Y, Sugimachi K. Natural history of hepatectomy regarding liver function: a study of both normal livers and livers with chronic hepatitis and cirrhosis. Hepatogastroenterology 1998;45:1795–1801.

    CAS  PubMed  Google Scholar 

  32. Veteläinen R, Bennink RJ, van Vliet AK, van Gulik TM. Mild steatosis impairs functional recovery after liver resection in an experimental model. Br J Surg 2007;94:1002–1008.

    Article  PubMed  Google Scholar 

  33. Oleszczuk A, Spannbauer M, Tannapfel A, Blüher M, Hengstler J, Pietsch UC, Schuhmacher A, Wittekind C, Hauss JP, Schön MR. Regenerative capacity differs between micro- and macrovesicular hepatic steatosis. Exp Toxicol Pathol 2007;59:205–213.

    Article  PubMed  Google Scholar 

  34. Covey AM, Brown KT, Jarnagin WR, Brody LA, Schwartz L, Tuorto S, Sofocleous CT, D'Angelica M, Getrajdman GI, DeMatteo R, Kemeny NE, Fong Y. Combined portal vein embolization and neoadjuvant chemotherapy as a treatment strategy for resectable hepatic colorectal metastases. Ann Surg 2008;247:451–455.

    Article  PubMed  Google Scholar 

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Correspondence to Kuniya Tanaka.

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Tanaka, K., Kumamoto, T., Matsuyama, R. et al. Influence of Chemotherapy on Liver Regeneration Induced by Portal Vein Embolization or First Hepatectomy of a Staged Procedure for Colorectal Liver Metastases. J Gastrointest Surg 14, 359–368 (2010). https://doi.org/10.1007/s11605-009-1073-6

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  • DOI: https://doi.org/10.1007/s11605-009-1073-6

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