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Open Access 01-02-2009 | Hepatobiliary and Pancreatic Tumors

Induction of Tumor Growth After Preoperative Portal Vein Embolization: Is It a Real Problem?

Authors: Wilmar de Graaf, Jacomina W. van den Esschert, Krijn P. van Lienden, Thomas M. van Gulik

Published in: Annals of Surgical Oncology | Issue 2/2009

Abstract

Although preoperative portal vein embolization (PVE) is an effective means to increase future remnant liver (FRL) volume, little has been published on possible adverse effects. This review discusses the clinical and experimental evidence regarding the effect of PVE on tumor growth in both embolized and nonembolized liver lobes, as well as potential strategies to control tumor progression after PVE. A literature review was performed using MEDLINE with keywords related to experimental and clinical studies concerning PVE, portal vein ligation (PVL), and tumor growth. Cross-references and references from reviews were also checked. Clinical and experimental data suggest that tumor progression can occur after preoperative PVE in embolized and nonembolized liver segments. Clinical evidence indicating possible tumor progression in patients with colorectal metastases or with primary liver tumors is based on studies with small sample size. Although multiple studies demonstrated tumor progression, evidence concerning a direct increase in tumor growth rate as a result of PVE is circumstantial. Three possible mechanisms influencing tumor growth after PVE can be recognized, namely changes in cytokines or growth factors, alteration in hepatic blood supply and an enhanced cellular host response promoting local tumor growth after PVE. Post-PVE chemotherapy and sequential transcatheter arterial chemoembolization (TACE) before PVE have been proposed to reduce tumor mass after PVE. We conclude that tumor progression can occur after PVE in patients with colorectal metastases as well as in patients with primary liver tumors. However, further research is needed in order to rate this risk of tumor progression after PVE.

Abulkhir A, Limongelli P, Healey AJ, et al. Preoperative portal vein embolization for major liver resection: a meta-analysis. Ann Surg. 2008;247:49–57.PubMed

Madoff DC, Abdalla EK, Vauthey JN. Portal vein embolization in preparation for major hepatic resection: evolution of a new standard of care. J Vasc Interv Radiol. 2005;16:779–90.PubMed

Hirai I, Kimura W, Fuse A, et al. Evaluation of preoperative portal embolization for safe hepatectomy, with special reference to assessment of nonembolized lobe function with 99 mTc-GSA SPECT scintigraphy. Surgery. 2003;133:495–506.PubMedCrossRef

Kubo S, Shiomi S, Tanaka H, et al. Evaluation of the effect of portal vein embolization on liver function by (99 m)tc-galactosyl human serum albumin scintigraphy. J Surg Res. 2002;107:113–8.PubMed

Nanashima A, Yamaguchi H, Shibasaki S, et al. Relationship between CT volumetry and functional liver volume using technetium–99 m galactosyl serum albumin scintigraphy in patients undergoing preoperative portal vein embolization before major hepatectomy: a preliminary study. Dig Dis Sci. 2006;51:1190–5.PubMedCrossRef

Uesaka K, Nimura Y, Nagino M. Changes in hepatic lobar function after right portal vein embolization. An appraisal by biliary indocyanine green excretion. Ann Surg. 1996;223:77–83.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

Hemming AW, Reed AI, Howard RJ, et al. Preoperative portal vein embolization for extended hepatectomy. Ann Surg. 2003;237:686–91.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

10.

Azoulay D, Castaing D, Krissat J, et al. Percutaneous portal vein embolization increases the feasibility and safety of major liver resection for hepatocellular carcinoma in injured liver. Ann Surg. 2000;232:665–72.PubMedCrossRef

11.

Azoulay D, Castaing D, Smail A, et al. Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization. Ann Surg. 2000;231:480–6.PubMedCrossRef

12.

Nagino M, Kamiya J, Nishio H, et al. Two hundred forty consecutive portal vein embolizations before extended hepatectomy for biliary cancer: surgical outcome and long-term follow-up. Ann Surg. 2006;243:364–72.PubMedCrossRef

13.

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

14.

Makuuchi M, Thai BL, Takayasu K, 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

15.

Abdalla EK, Barnett CC, Doherty D, et al. Extended hepatectomy in patients with hepatobiliary malignancies with and without preoperative portal vein embolization. Arch Surg. 2002;137:675–80.PubMedCrossRef

16.

Abdalla EK, Adam R, Bilchik AJ, et al. Improving resectability of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol. 2006;13:1271–80.PubMedCrossRef

17.

Schindl MJ, Redhead DN, Fearon KC, et al. The value of residual liver volume as a predictor of hepatic dysfunction and infection after major liver resection. Gut. 2005;54:289–96.PubMedCrossRef

18.

Elias D, de BT, Roche A, et al. 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

19.

Barbaro B, Di SC, Nuzzo G, et al. Preoperative right portal vein embolization in patients with metastatic liver disease. Metastatic liver volumes after RPVE. Acta Radiol. 2003;44:98–102.PubMedCrossRef

20.

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

21.

Heinrich S, Jochum W, Graf R, et al. Portal vein ligation and partial hepatectomy differentially influence growth of intrahepatic metastasis and liver regeneration in mice. J Hepatol. 2006;45:35–42.PubMedCrossRef

22.

Kawasaki S, Makuuchi M, Kakazu T, et al. Resection for multiple metastatic liver tumors after portal embolization. Surgery. 1994;115:674–7.PubMed

23.

Jaeck D, Oussoultzoglou E, Rosso E, et al. 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.PubMedCrossRef

24.

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

25.

Imamura H, Shimada R, Kubota M, et al. Preoperative portal vein embolization: an audit of 84 patients. Hepatology. 1999;29:1099–105.PubMedCrossRef

26.

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

27.

Alwayn IP, Verbesey JE, Kim S, et al. A critical role for matrix metalloproteinases in liver regeneration. J Surg Res. 2008;145:192–8.PubMedCrossRef

28.

Mook OR, Frederiks WM, Van Noorden CJ. The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys Acta. 2004;1705:69–89.PubMed

29.

Taub R. Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol. 2004;5:836–47.PubMedCrossRef

30.

Nabeshima K, Shimao Y, Inoue T, et al. Hepatocyte growth factor/scatter factor induces not only scattering but also cohort migration of human colorectal-adenocarcinoma cells. Int J Cancer. 1998;78:750–9.PubMedCrossRef

31.

Brozek W, Bises G, Girsch T, et al. Differentiation-dependent expression and mitogenic action of interleukin–6 in human colon carcinoma cells: relevance for tumour progression. Eur J Cancer. 2005;41:2347–54.PubMedCrossRef

32.

Otte JM, Schmitz F, Kiehne K, et al. Functional expression of HGF and its receptor in human colorectal cancer. Digestion. 2000;61:237–46.PubMedCrossRef

33.

Fazekas K, Csuka O, Köves I, et al. Experimental and clinicopathologic studies on the function of the HGF receptor in human colon cancer metastasis. Clin Exp Metastasis. 2000;18:639–49.PubMedCrossRef

34.

Shimizu Y, Suzuki H, Nimura Y, et al. Elevated mitochondrial gene expression during rat liver regeneration after portal vein ligation. Hepatology. 1995;22:1222–9.PubMed

35.

Starkel P, Horsmans Y, Sempoux C, 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

36.

Uemura T, Miyazaki M, Hirai 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

37.

Kollmar O, Corsten M, Scheuer C, et al. 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

38.

Harris AL. Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer. 2002;2:38–47.PubMedCrossRef

39.

Semenza GL. Hypoxia and cancer. Cancer Metastasis Rev. 2007;26:223–4.PubMedCrossRef

40.

Xu Y, Pasche B. TGF-beta signaling alterations and susceptibility to colorectal cancer. Hum Mol Genet. 2007;16 Spec no 1:R14–20.

41.

Rocheleau B, Ethier C, Houle R, et al. Hepatic artery buffer response following left portal vein ligation: its role in liver tissue homeostasis. Am J Physiol. 1999;277:G1000–7.PubMed

42.

Lautt WW. Mechanism and role of intrinsic regulation of hepatic arterial blood flow: hepatic arterial buffer response. Am J Physiol. 1985;249:G549–56.PubMed

43.

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

44.

Yokoyama Y, Wawrzyniak A, Sarmadi AM, et al. Hepatic arterial flow becomes the primary supply of sinusoids following partial portal vein ligation in rats. J Gastroenterol Hepatol. 2006;21:1567–74.PubMedCrossRef

45.

Mueller L, Goettsche J, Abdulgawad A, et al. Tumor growth-promoting cellular host response during liver atrophy after portal occlusion. Liver Int. 2005;25:994–1001.PubMedCrossRef

46.

Bajou K, Noel A, Gerard RD, et al. Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat Med. 1998;4:923–8.PubMedCrossRef

47.

Tanaka S, Akaike T, Fang J, et al. Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour. Br J Cancer. 2003;88:902–9.PubMedCrossRef

48.

Jozkowicz A, Was H, Dulak J. Heme oxygenase-1 in tumors: is it a false friend? Antioxid Redox Signal. 2007;9:2099–117.PubMedCrossRef

49.

Busserolles J, Megias J, Terencio MC, et al. Heme oxygenase-1 inhibits apoptosis in Caco-2 cells via activation of Akt pathway. Int J Biochem Cell Biol. 2006;38:1510–7.PubMedCrossRef

50.

Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005;10:86–103.PubMedCrossRef

51.

Aoki T, Imamura H, Hasegawa K, et al. Sequential preoperative arterial and portal venous embolizations in patients with hepatocellular carcinoma. Arch Surg. 2004;139:766–74.PubMedCrossRef

52.

Yamakado K, Takeda K, Matsumura K, et al. Regeneration of the un-embolized liver parenchyma following portal vein embolization. J Hepatol. 1997;27:871–80.PubMedCrossRef

53.

Nakao N, Miura K, Takahashi H, et al. Hepatocellular carcinoma: combined hepatic, arterial, and portal venous embolization. Radiology. 1986;161:303–7.PubMed

54.

Ogata S, Belghiti J, Farges O, et al. Sequential arterial and portal vein embolizations before right hepatectomy in patients with cirrhosis and hepatocellular carcinoma. Br J Surg. 2006;93:1091–8.PubMedCrossRef

55.

Yamakado K, Nakatsuka A, Tanaka N, et al. Long-term follow-up arterial chemoembolization combined with transportal ethanol injection used to treat hepatocellular carcinoma. J Vasc Interv Radiol. 1999;10:641–7.PubMedCrossRef

56.

Vetelainen R, Dinant S, van VA, et al. Portal vein ligation is as effective as sequential portal vein and hepatic artery ligation in inducing contralateral liver hypertrophy in a rat model. J Vasc Interv Radiol. 2006;17:1181–8.PubMedCrossRef

57.

Vogl TJ, Mack MG, Balzer JO, et al. Liver metastases: neoadjuvant downsizing with transarterial chemoembolization before laser-induced thermotherapy. Radiology. 2003;229:457–64.PubMedCrossRef

58.

Nabil M, Gruber T, Yakoub D, et al. Repetitive transarterial chemoembolization (TACE) of liver metastases from renal cell carcinoma: local control and survival results. Eur Radiol. 2008;18:1456–63.PubMedCrossRef

59.

Vogl TJ, Zangos S, Eichler K, et al. Colorectal liver metastases: regional chemotherapy via transarterial chemoembolization (TACE) and hepatic chemoperfusion: an update. Eur Radiol. 2007;17:1025–34.PubMedCrossRef

60.

Beal IK, Anthony S, Papadopoulou A, et al. Portal vein embolisation prior to hepatic resection for colorectal liver metastases and the effects of periprocedure chemotherapy. Br J Radiol. 2006;79:473–8.PubMedCrossRef

61.

Goere D, Farges O, Leporrier J, et al. Chemotherapy does not impair hypertrophy of the left liver after right portal vein obstruction. J Gastrointest Surg. 2006;10:365–70.PubMedCrossRef

62.

Covey AM, Brown KT, Jarnagin WR, et al. Combined portal vein embolization and neoadjuvant chemotherapy as a treatment strategy for resectable hepatic colorectal metastases. Ann Surg. 2008;247:451–5.PubMedCrossRef

63.

Selzner N, Pestalozzi BC, Kadry Z, et al. Downstaging colorectal liver metastases by concomitant unilateral portal vein ligation and selective intra-arterial chemotherapy. Br J Surg. 2006;93:587–92.PubMedCrossRef

64.

Abdalla EK, Hicks ME, Vauthey JN. Portal vein embolization: rationale, technique and future prospects. Br J Surg. 2001;88:165–75.PubMedCrossRef

65.

Nishiyama Y, Yamamoto Y, Hino I, et al. 99mTc galactosyl human serum albumin liver dynamic SPET for pre-operative assessment of hepatectomy in relation to percutaneous transhepatic portal embolization. Nucl Med Commun. 2003;24:809–17.PubMedCrossRef

66.

Benoist S, Nordlinger B. Neoadjuvant treatment before resection of liver metastases. Eur J Surg Oncol. 2007;33(Suppl 2):S35–41.PubMed

Title: Induction of Tumor Growth After Preoperative Portal Vein Embolization: Is It a Real Problem?
Authors: Wilmar de Graaf
Jacomina W. van den Esschert
Krijn P. van Lienden
Thomas M. van Gulik
Publication date: 01-02-2009
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 2/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-008-0222-6

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Induction of Tumor Growth After Preoperative Portal Vein Embolization: Is It a Real Problem?

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