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Ultraschall Med 2015; 36(02): 132-139
DOI: 10.1055/s-0034-1399147
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

CEUS in Hepatocellular Carcinoma and Intrahepatic Cholangiocellular Carcinoma in 320 Patients – Early or Late Washout Matters: A Subanalysis of the DEGUM Multicenter Trial

Kontrastverstärkter Ultraschall bei 320 Patienten mit hepatozellulären und intrahepatischen cholangiozellulären Karzinomen – frühes oder spätes Auswaschen macht den Unterschied. Subanalyse der DEGUM Multicenter Studie
D. Wildner
1   Department of Internal Medicine 1, University Hospital Erlangen, Germany
,
T. Bernatik
2   Department of Internal Medicine, District Hospital Ebersberg, Germany
,
C. Greis
3   Department of Clinical Research, Bracco Imaging Deutschland, Konstanz, Germany
,
K. Seitz
4   Department of Medicine, District Hospital Sigmaringen, Germany
,
M. F. Neurath
1   Department of Internal Medicine 1, University Hospital Erlangen, Germany
,
D. Strobel
1   Department of Internal Medicine 1, University Hospital Erlangen, Germany
› Author Affiliations
Further Information

Publication History

03 September 2014

23 January 2015

Publication Date:
26 March 2015 (online)

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Abstract

Purpose: The aim of the study was the comparison of tumor vascularization and contrast enhancement in contrast-enhanced ultrasound (CEUS) for the characterization of hepatocellular carcinoma (HCC) and intrahepatic cholangiocellular carcinoma (ICC). We present data of the subpopulations HCC and ICC examined in the DEGUM multicenter trial for the characterization of focal liver lesions in clinical practice.

Materials and Methods: Based on the data of the DEGUM multicenter trial (1349 patients), all patients with histologically proven HCC (n = 278) and ICC (n = 42) were analyzed. The vascularity pattern and contrast enhancement pattern during the arterial, portal-venous and late phase were compared.

Results: An underlying liver cirrhosis was found in 214/278 patients with HCC (76.9 %) and 7/42 patients with ICC (16.7 %). In CEUS, HCC showed a global arterial hyperenhancement compared to ICC (HCC: tumor center: 60.3 %; tumor periphery: 75 %; ICC: tumor center: 16.7 %; tumor periphery: 40.5 %). ICC showed an initial contrast enhancement primarily at the tumor periphery (ICC: 85.7 % vs. HCC: 61 %) followed by an early portal-venous contrast washout in the tumor center (ICC: 85.8 % vs. HCC: 49.8 %) and tumor periphery (ICC: 66.7 % vs. HCC: 32.6 %). HCC showed a delayed contrast washout (late phase hypoenhancement: HCC: 75 % vs. ICC: 92.9 %).

Conclusion: ICCs are rare in cirrhotic livers. CEUS can demonstrate differences in the vascularization patterns between HCC and ICC. HCC showed an arterial global hyperenhancement and delayed contrast washout in the late phase. ICCs are characterized by an arterial contrast enhancement at the tumor periphery with early contrast washout of the vascularized parts of the lesions in the portal-venous and late phase.

Zusammenfassung

Ziel: Ziel dieser Arbeit war es, die Vaskularisationsmuster von hepatozellulären (HCC) und intrahepatischen cholangiozellulären Karzinomen (ICC) in der Kontrastmittelsonografie (CEUS) zu vergleichen. Es handelt sich um eine Subanalyse der DEGUM – Multizenterstudie zum Stellenwert der Kontrastmittelsonografie von B-Bild-morphologisch unklaren Leberläsionen.

Material und Methoden: Aus der Datenbank der DEGUM Multizenterstudie (1349 Patienten) wurden alle histologisch gesicherten HCC (n = 278) und ICC (n = 42) analysiert. Dazu wurden die Vaskularisationsmuster und das Kontrastmittelenhancement der hämodynamisch relevanten Perfusionsphasen (arteriell, portal-venös, Spätphase) verglichen.

Ergebnisse: Bei 214/278 Patienten mit HCC (76.9 %) und bei 7/42 Patienten mit ICC (16.7 %) lag eine Leberzirrhose vor. In CEUS zeigten HCC im Vergleich zu ICC häufiger eine arterielle Hypervaskularisation (HCC: Tumorzentrum: 60.3 %; Tumorperipherie: 75 %. ICC: Tumorzentrum 16.7 %; Tumorperipherie 40.5 %). ICC zeigten in der portalvenösen Phase häufiger ein Hypoenhancement (Zentrum der Läsion: ICC: 85.8 % vs. HCC: 49.8 %. Peripherie: ICC 66.7 % vs. HCC 32.6 %). In der Spätphase zeigten die Mehrzahl der HCC (75 %) und nahezu alle ICC (92.9 %) ein Auswaschen des Kontrastmittels.

Schlussfolgerung: Die Differentialdiagnose eines ICC bei Leberzirrhose ist selten. In der CEUS zeigen HCC und ICC unterschiedliche Vaskularisationsmuster. Charakteristisch für ein HCC sind die globale arterielle KM-Aufnahme und ein langsames Auswaschen des Kontrastmittels in der Spätphase. Charakteristisch für ICC ist die initiale Kontrastmittelanflutung vorwiegend in der Tumorperipherie mit Auswaschen des Kontrastmittels ab der frühen portalvenösen Phase.

Key words

contrast-enhanced ultrasound - hepatocellular carcinoma - intrahepatic cholangiocellular carcinoma - enhancement pattern - characterization
 

  • References

  • 1 Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020-1022
    CrossrefPubMedGoogle Scholar
  • 2 EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012; 56: 908-943
    CrossrefPubMedGoogle Scholar
  • 3 Vilana R, Forner A, Bianchi L et al. Intrahepatic peripheral cholangiocarcinoma in cirrhosis patients may display a vascular pattern similar to hepatocellular carcinoma on contrast-enhanced ultrasound. Hepatology 2010; 51: 2020-2029
    CrossrefPubMedGoogle Scholar
  • 4 Rimola J, Forner A, Reig M et al. Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma. Hepatology 2009; 50: 791-798
    CrossrefPubMedGoogle Scholar
  • 5 Strobel D, Seitz K, Blank W et al. Contrast-enhanced ultrasound for the characterization of focal liver lesions--diagnostic accuracy in clinical practice (DEGUM multicenter trial). Ultraschall in Med 2008; 29: 499-505
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Strobel D, Seitz K, Blank W et al. Tumor-specific vascularization pattern of liver metastasis, hepatocellular carcinoma, hemangioma and focal nodular hyperplasia in the differential diagnosis of 1349 liver lesions in contrast-enhanced ultrasound (CEUS). Ultraschall in Med 2009; 30: 376-382
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Seitz K, Strobel D, Bernatik T et al. Contrast-Enhanced Ultrasound (CEUS) for the characterization of focal liver lesions – prospective comparison in clinical practice: CEUS vs. CT (DEGUM multicenter trial). Parts of this manuscript were presented at the Ultrasound Dreilandertreffen 2008, Davos. Ultraschall in Med 2009; 30: 383-389
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Seitz K, Bernatik T, Strobel D et al. Contrast-enhanced ultrasound (CEUS) for the characterization of focal liver lesions in clinical practice (DEGUM Multicenter Trial): CEUS vs. MRI – a prospective comparison in 269 patients. Ultraschall in Med 2010; 31: 492-499
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Claudon M, Dietrich CF, Choi BI et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver--update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultraschall in Med 2013; 34: 11-29
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Jemal A, Bray F, Center MM et al. Global cancer statistics. CA: a cancer. J CLIN 2011; 61: 69-90
    PubMedGoogle Scholar
  • 11 Song P, Tobe RG, Inagaki Y et al. The management of hepatocellular carcinoma around the world: a comparison of guidelines from 2001 to 2011. Liver INT 2012; 32: 1053-1063
    CrossrefPubMedGoogle Scholar
  • 12 Barreiros AP, Piscaglia F, Dietrich CF. Contrast enhanced ultrasound for the diagnosis of hepatocellular carcinoma (HCC): comments on AASLD guidelines. J Hepatol 2012; 57: 930-932
    CrossrefPubMedGoogle Scholar
  • 13 Dietrich CF, Cui XW, Boozari B et al. Contrast-enhanced ultrasound (CEUS) in the diagnostic algorithm of hepatocellular and cholangiocellular carcinoma, comments on the AASLD guidelines. Ultraschall in Med 2012; 1: S57-S66
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Bota S, Piscaglia F, Marinelli S et al. Comparison of International Guidelines for Noninvasive Diagnosis of Hepatocellular Carcinoma. Liver Cancer 2012; 1: 190-200
    CrossrefPubMedGoogle Scholar
  • 15 Giorgio A, Calisti G, Giorgio V. CEUS and HCC: are the 2008 EFSUMB guidelines still valid or has their wash-out already started?. Ultraschall in Med 2011; 32: 315-316
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Iavarone M, Piscaglia F, Vavassori S et al. Contrast enhanced CT-scan to diagnose intrahepatic cholangiocarcinoma in patients with cirrhosis. J Hepatol 2013; 58: 1188-1193
    CrossrefPubMedGoogle Scholar
  • 17 Forner A, Vilana R, Ayuso C et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 2008; 47: 97-104
    CrossrefPubMedGoogle Scholar
  • 18 Dai Y, Chen MH, Fan ZH et al. Diagnosis of small hepatic nodules detected by surveillance ultrasound in patients with cirrhosis: Comparison between contrast-enhanced ultrasound and contrast-enhanced helical computed tomography. Hepatology Res 2008; 38: 281-290
    CrossrefPubMedGoogle Scholar
  • 19 Hatanaka K, Kudo M, Minami Y et al. Sonazoid-enhanced ultrasonography for diagnosis of hepatic malignancies: comparison with contrast-enhanced CT. Oncology 2008; 75: 42-47
    CrossrefPubMedGoogle Scholar
  • 20 Trillaud H, Bruel JM, Valette PJ et al. Characterization of focal liver lesions with SonoVue-enhanced sonography: international multicenter-study in comparison to CT and MRI. World J Gastroenterol 2009; 15: 3748-3756
    CrossrefPubMedGoogle Scholar
  • 21 Floriani I, D'Onofrio M, Rulli E et al. Performance of imaging modalities in the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Ultraschall in Med 2013; 34: 454-462
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Claudon M, Cosgrove D, Albrecht T et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) – update 2008. Ultraschall in Med 2008; 29: 28-44
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Choi JY, Lee JM, Sirlin CB. CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. Development, growth, and spread: key pathologic and imaging aspects. Radiology 2014; 272: 635-654
    CrossrefPubMedGoogle Scholar
  • 24 Choi JY, Lee JM, Sirlin CB. CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part II. Extracellular agents, hepatobiliary agents, and ancillary imaging features. Radiology 2014; 273: 30-50
    CrossrefPubMedGoogle Scholar
  • 25 Komuta M, Govaere O, Vandecaveye V et al. Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes. Hepatology 2012; 55: 1876-1888
    CrossrefPubMedGoogle Scholar
  • 26 Kang Y, Lee JM, Kim SH et al. Intrahepatic mass-forming cholangiocarcinoma: enhancement patterns on gadoxetic acid-enhanced MR images. Radiology 2012; 264: 751-760
    CrossrefPubMedGoogle Scholar
  • 27 Thian YL, Riddell AM, Koh DM. Liver-specific agents for contrast-enhanced MRI: role in oncological imaging. Cancer Imaging 2013; 13: 567-579
    CrossrefPubMedGoogle Scholar
  • 28 Xu HX, Lu MD, Liu GJ et al. Imaging of peripheral cholangiocarcinoma with low-mechanical index contrast-enhanced sonography and SonoVue: initial experience. J Ultrasound in Med 2006; 25: 23-33
    PubMedGoogle Scholar
  • 29 Chen LD, Xu HX, Xie XY et al. Enhancement patterns of intrahepatic cholangiocarcinoma: comparison between contrast-enhanced ultrasound and contrast-enhanced CT. Br J Radiology 2008; 81: 881-889
    CrossrefPubMedGoogle Scholar
  • 30 D'Onofrio M, Vecchiato F, Cantisani V et al. Intrahepatic peripheral cholangiocarcinoma (IPCC): comparison between perfusion ultrasound and CT imaging. Radiol Med 2008; 113: 76-86
    CrossrefPubMedGoogle Scholar
  • 31 Chen LD, Xu HX, Xie XY et al. Intrahepatic cholangiocarcinoma and hepatocellular carcinoma: differential diagnosis with contrast-enhanced ultrasound. Eur Radiol 2010; 20: 743-753
    CrossrefPubMedGoogle Scholar
  • 32 Bohle W, Clemens PU, Heubach T et al. Contrast-enhanced ultrasound (CEUS) for differentiating between hepatocellular and cholangiocellular carcinoma. Ultraschall in Med 2012; 33: E191-E195
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Xu HX, Chen LD, Liu LN et al. Contrast-enhanced ultrasound of intrahepatic cholangiocarcinoma: correlation with pathological examination. Br J Radiol 2012; 85: 1029-1037
    CrossrefPubMedGoogle Scholar
  • 34 Galassi M, Iavarone M, Rossi S et al. Patterns of appearance and risk of misdiagnosis of intrahepatic cholangiocarcinoma in cirrhosis at contrast enhanced ultrasound. Liver Int 2013; 33: 771-779
    CrossrefPubMedGoogle Scholar
  • 35 Li R, Yuan MX, Ma KS et al. Detailed analysis of temporal features on contrast enhanced ultrasound may help differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma in cirrhosis. PloS one 2014; 9: e98612
    CrossrefPubMedGoogle Scholar
  • 36 Wildner D, Pfeifer L, Goertz RS et al. Dynamic Contrast-Enhanced Ultrasound (DCE-US) for the Characterization of Hepatocellular Carcinoma and Cholangiocellular Carcinoma. Ultraschall in Med 2014; 35: 522-527
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Bernatik T, Seitz K, Blank W et al. Unclear focal liver lesions in contrast-enhanced ultrasonography--lessons to be learned from the DEGUM multicenter study for the characterization of liver tumors. Ultraschall in Med 2010; 31: 577-581
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Seitz K, Greis C, Schuler A et al. Frequency of tumor entities among liver tumors of unclear etiology initially detected by sonography in the noncirrhotic or cirrhotic livers of 1349 patients. Results of the DEGUM multicenter study. Ultraschall in Med 2011; 32: 598-603
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Greten TF, Malek NP, Schmidt S et al. Diagnosis of and therapy for hepatocellular carcinoma. Z Gastroenterol 2013; 51: 1269-1326
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet 2014; 383: 2168-2179
    Google Scholar
  • 41 Boozari B, Soudah B, Rifai K et al. Grading of hypervascular hepatocellular carcinoma using late phase of contrast enhanced sonography – a prospective study. Dig Liver Dis 2011; 43: 484-490
    CrossrefPubMedGoogle Scholar
  • 42 Chen MH, Dai Y, Yan K et al. The role of contrast-enhanced ultrasound on the diagnosis of small hepatocellular carcinoma (</=3cm) in patients with cirrhosis. Hepatol Res 2006; 35: 281-288
    CrossrefPubMedGoogle Scholar
  • 43 Friedrich-Rust M, Klopffleisch T, Nierhoff J et al. Contrast-Enhanced Ultrasound for the differentiation of benign and malignant focal liver lesions: a meta-analysis. Liver Int 2013; 33: 739-755
    CrossrefPubMedGoogle Scholar
  • 44 Tranquart F, Correas JM, Ladam MarcusV et al. [Real-time contrast-enhanced ultrasound in the evaluation of focal liver lesions: diagnostic efficacy and economical issues from a French multicentric study]. J Radiol 2009; 90: 109-122
    PubMedGoogle Scholar
  • 45 Sporea I, Badea R, Popescu A et al. Contrast-enhanced ultrasound (CEUS) for the evaluation of focal liver lesions – a prospective multicenter study of its usefulness in clinical practice. Ultraschall in Med 2014; 35: 259-266
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Westwood M, Joore M, Grutters J et al. Contrast-enhanced ultrasound using SonoVue(R) (sulphur hexafluoride microbubbles) compared with contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging for the characterisation of focal liver lesions and detection of liver metastases: a systematic review and cost-effectiveness analysis. Health Technol Assess 2013; 17: 1-243
    PubMedGoogle Scholar
  • 47 Sirli R, Sporea I, Martie A et al. Contrast enhanced ultrasound in focal liver lesions--a cost efficiency study. Med Ultrason 2010; 12: 280-285
    PubMedGoogle Scholar
  • 48 Giesel FL, Delorme S, Sibbel R et al. Contrast-enhanced ultrasound for the characterization of incidental liver lesions – an economical evaluation in comparison with multi-phase computed tomography. Ultraschall in Med 2009; 30: 259-268
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Kudo M, Izumi N, Kokudo N et al. Management of hepatocellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis 2011; 29: 339-364
    CrossrefPubMedGoogle Scholar
  • 50 Omata M, Lesmana LA, Tateishi R et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 2010; 4: 439-474
    CrossrefPubMedGoogle Scholar