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Ultraschall Med 2012; 33(S 01): S57-S66
DOI: 10.1055/s-0032-1312903
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© Georg Thieme Verlag KG Stuttgart · New York

Contrast-Enhanced Ultrasound (CEUS) in the Diagnostic Algorithm of Hepatocellular and Cholangiocellular Carcinoma, Comments on the AASLD Guidelines

Kontrastverstärkte Sonografie (CEUS) im Diagnose-Algorithmus des hepatozellulären und cholangiozellulären Karzinoms, Kommentar zu den AASLD-Leitlinien
C. F. Dietrich
1   Department of Internal Medicine 2, Caritas-Krankenhaus Bad Mergentheim, Academic Teaching Hospital of the University of Würzburg, Germany
,
X. W. Cui
1   Department of Internal Medicine 2, Caritas-Krankenhaus Bad Mergentheim, Academic Teaching Hospital of the University of Würzburg, Germany
,
B. Boozari
2   Medical Clinic I, Department of Hepatology, Gastroenterology and Infectiology, University of Tübingen, Germany
,
M. Hocke
3   Department of Internal Medicine 2, Hospital Meiningen, Germany
,
A. Ignee
1   Department of Internal Medicine 2, Caritas-Krankenhaus Bad Mergentheim, Academic Teaching Hospital of the University of Würzburg, Germany
› Author Affiliations
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Publication History

Publication Date:
21 June 2012 (online)

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Abstract

Contrast-enhanced ultrasound (CEUS) has long been present in important guidelines and recommendations for the diagnostic work-up of focal liver lesions in patients with cirrhosis. These guidelines have included the guidelines of the American Association for the Study of Liver Diseases (AASLD) 2005, the Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma, the recommendations of the Japanese Society of Hepatology, and the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 (in preparation). Recently, the AASLD removed CEUS from their guidelines in part because of the perceived possibility of false-positive hepatocellular carcinoma (HCC) diagnosis in patients with intrahepatic cholangiocarcinoma (ICC), and in part because CEUS is not available in the USA. This latter factor means that published results are not entirely applicable to a North American population. The present manuscript discusses the diagnostic algorithm of hepatocellular carcinoma and provides information on the differential diagnosis between HCC and ICC.

Zusammenfassung

Kontrastverstärkte Ultraschalltechniken (CEUS) haben sich im letzten Jahrzehnt etabliert und sind immanenter Bestandteil aktueller Leitlinien. Kürzlich wurde in den AASLD-Leitlinien die kontrastverstärkte Sonografie mit der Begründung eliminiert, dass in Einzelfällen cholangiozelluläre Karzinome mit hepatozellulären Karzinomen verwechselt werden können. Als weiterer Grund wurde angegeben, dass die in Europa, Kanada und Asien publizierten Daten nicht vollständig auf die amerikanische Bevölkerung übertragbar sind. In der folgenden Arbeit wird erläutert, warum diese Entscheidung der AASLD irreführend ist und korrigiert werden muss.

Key words

diagnosis - characterization - metastases - liver tumor - focal nodular hyperplasia - hemangioma
 

  • References

  • 1 Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005; 42: 1208-1236
    CrossrefPubMedGoogle Scholar
  • 2 Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020-1022
    CrossrefPubMedGoogle Scholar
  • 3 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
  • 4 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
  • 5 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
  • 6 Giorgio A, Calisti G, Giorgio V. CEUS and HCC: are the 2008 EFSUMB guidelines still valid or has their washout already started?. Ultraschall in Med 2011; 32: 315-316
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Kumar M, Zhao X, Wang XW. Molecular carcinogenesis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: one step closer to personalized medicine?. Cell Biosci 2011; 1: 5
    CrossrefPubMedGoogle Scholar
  • 8 Ignee A, Weiper D, Schuessler G et al. Sonographic characterisation of hepatocellular carcinoma at time of diagnosis. Z Gastroenterol 2005; 43: 289-294
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Cui XW, Ignee A, Braden B et al. Biliary Papillomatosis and New Ultrasound Imaging Modalities. Z Gastroenterol 2012; 50: 226-231
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Dietrich CF, Jenssen C. Evidence based endoscopic ultrasound. Z Gastroenterol 2011; 49: 599-621
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Bhayana D, Kim TK, Jang HJ et al. Hypervascular liver masses on contrast-enhanced ultrasound: the importance of washout. Am J Roentgenol 2010; 194: 977-983
    CrossrefPubMedGoogle Scholar
  • 12 Wilson SR, Greenbaum LD, Goldberg BB. Contrast-enhanced ultrasound: what is the evidence and what are the obstacles?. Am J Roentgenol 2009; 193: 55-60
    CrossrefPubMedGoogle Scholar
  • 13 Morel DR, Schwieger I, Hohn L et al. Human pharmacokinetics and safety evaluation of SonoVue, a new contrast agent for ultrasound imaging. Invest Radiol 2000; 35: 80-85
    CrossrefPubMedGoogle Scholar
  • 14 Piscaglia F, Nolsoe C, Dietrich CF et al. The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): Update 2011 on non-hepatic applications. Ultraschall in Med 2011; DOI: 10.1055/s-0031-1281676.
    PubMedGoogle Scholar
  • 15 Piscaglia F, Bolondi L. The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations. Ultrasound Med Biol 2006; 32: 1369-1375
    CrossrefPubMedGoogle Scholar
  • 16 Aggeli C, Giannopoulos G, Lampropoulos K et al. Adverse bioeffects of ultrasound contrast agents used in echocardiography: true safety issue or “much ado about nothing”?. Curr Vasc Pharmacol 2009; 7: 338-346
    CrossrefPubMedGoogle Scholar
  • 17 Aggeli C, Giannopoulos G, Roussakis G et al. Safety of myocardial flash-contrast echocardiography in combination with dobutamine stress testing for the detection of ischaemia in 5250 studies. Heart 2008; 94: 1571-1577
    CrossrefPubMedGoogle Scholar
  • 18 Dietrich CF, Ignee A, Hocke M et al. Pitfalls and artefacts using contrast enhanced ultrasound. Z Gastroenterol 2011; 49: 350-356
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Dietrich CF, Schuessler G, Trojan J et al. Differentiation of focal nodular hyperplasia and hepatocellular adenoma by contrast-enhanced ultrasound. Br J Radiol 2005; 78: 704-707
    CrossrefPubMedGoogle Scholar
  • 20 Dietrich CF, Ignee A, Trojan J et al. Improved characterisation of histologically proven liver tumours by contrast enhanced ultrasonography during the portal venous and specific late phase of SHU 508A. Gut 2004; 53: 401-405
    CrossrefPubMedGoogle Scholar
  • 21 Dietrich CF, Mertens JC, Braden B et al. Contrast-enhanced ultrasound of histologically proven liver hemangiomas. Hepatology 2007; 45: 1139-1145
    CrossrefPubMedGoogle Scholar
  • 22 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
  • 23 Dietrich CF, Wehrmann T, Zeuzem S et al. Analysis of hepatic echo patterns in chronic hepatitis C. Ultraschall in Med 1999; 20: 9-14
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 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
  • 25 Yang ZF, Poon RT. Vascular changes in hepatocellular carcinoma. Anat Rec (Hoboken) 2008; 291: 721-734
    CrossrefPubMedGoogle Scholar
  • 26 Schacherer D, Girlich C, Wiest R et al. Semiquantitative characterization of hepatocellular carcinoma (HCC) – perfusion with contrast-enhanced ultrasound and perfusion analysis. Clin Hemorheol Microcirc 2010; 44: 97-105
    PubMedGoogle Scholar
  • 27 Burns PN, Wilson SR. Focal liver masses: enhancement patterns on contrast-enhanced images – concordance of US scans with CT scans and MR images. Radiology 2007; 242: 162-174
    CrossrefPubMedGoogle Scholar
  • 28 Chen LD, Xu HX, Xie XY et al. Enhancement patterns of intrahepatic cholangiocarcinoma: comparison between contrast-enhanced ultrasound and contrast-enhanced CT. Br J Radiol 2008; 81: 881-889
    CrossrefPubMedGoogle Scholar
  • 29 Jang HJ, Kim TK, Burns PN et al. Enhancement patterns of hepatocellular carcinoma at contrast-enhanced US: comparison with histologic differentiation. Radiology 2007; 244: 898-906
    CrossrefPubMedGoogle Scholar
  • 30 Liu GJ, Xu HX, Lu MD et al. Correlation between enhancement pattern of hepatocellular carcinoma on real-time contrast-enhanced ultrasound and tumour cellular differentiation on histopathology. Br J Radiol 2007; 80: 321-330
    CrossrefPubMedGoogle Scholar
  • 31 Kim TK, Lee KH, Khalili K et al. Hepatocellular nodules in liver cirrhosis: contrast-enhanced ultrasound. Abdom Imaging 2011; 36: 244-263
    CrossrefPubMedGoogle Scholar
  • 32 Martie A, Sporea I, Popescu A et al. Contrast enhanced ultrasound for the characterization of hepatocellular carcinoma. Med Ultrason 2011; 13: 108-113
    PubMedGoogle Scholar
  • 33 Nicolau C, Catala V, Vilana R et al. Evaluation of hepatocellular carcinoma using SonoVue, a second generation ultrasound contrast agent: correlation with cellular differentiation. Eur Radiol 2004; 14: 1092-1099
    CrossrefPubMedGoogle Scholar
  • 34 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
  • 35 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 Dreiländertreffen 2008, Davos. Ultraschall in Med 2009; 30: 383-389
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 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
  • 37 Nicolau C, Vilana R, Bru C. The use of contrast-enhanced ultrasound in the management of the cirrhotic patient and for detection of HCC. Eur Radiol 2004; 14: 63-71
    CrossrefPubMedGoogle Scholar
  • 38 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
  • 39 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
  • 40 Strobel D, Bernatik T, Blank W et al. Diagnostic accuracy of CEUS in the differential diagnosis of small (≤20 mm) and subcentimetric (≤ 10 mm) focal liver lesions in comparison with histology. Results of the DEGUM multicenter trial. Ultraschall in Med 2011; 32: 593-597
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 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 1,349 liver lesions in contrast-enhanced ultrasound (CEUS). Ultraschall in Med 2009; 30: 376-382
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Xiao JD, Zhu WH, Shen SR. Evaluation of hepatocellular carcinoma using contrast-enhanced ultrasonography: correlation with microvessel morphology. Hepatobiliary Pancreat Dis Int 2010; 9: 605-610
    PubMedGoogle Scholar
  • 43 Zhou YM, Yang JM, Li B et al. Clinicopathologic characteristics of intrahepatic cholangiocarcinoma in patients with positive serum a-fetoprotein. World J Gastroenterol 2008; 14: 2251-2254
    CrossrefPubMedGoogle Scholar
  • 44 Shen WF, Zhong W, Xu F et al. Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma. World J Gastroenterol 2009; 15: 5976-5982
    CrossrefPubMedGoogle Scholar
  • 45 Tao LY, Cai L, He XD et al. Comparison of serum tumor markers for intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Am Surg 2010; 76: 1210-1213
    PubMedGoogle Scholar
  • 46 Uenishi T, Kubo S, Yamamoto T et al. Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence. Cancer Sci 2003; 94: 851-857
    CrossrefPubMedGoogle Scholar
  • 47 Sparchez Z, Radu P, Zaharia T et al. Usefulness of contrast enhanced ultrasound guidance in percutaneous biopsies of liver tumors. J Gastrointestin Liver Dis 2011; 20: 191-196
    PubMedGoogle Scholar
  • 48 Kim TK, Lee KH, Jang HJ et al. Analysis of gadobenate dimeglumine-enhanced MR findings for characterizing small (1–2-cm) hepatic nodules in patients at high risk for hepatocellular carcinoma. Radiology 2011; 259: 730-738
    CrossrefPubMedGoogle Scholar
  • 49 Postema M, Gilja OH. Contrast-enhanced and targeted ultrasound. World J Gastroenterol 2011; 17: 28-41
    CrossrefPubMedGoogle Scholar
  • 50 Sporea I, Sirli R, Martie A et al. How useful is contrast enhanced ultrasonography for the characterization of focal liver lesions?. J Gastrointestin Liver Dis 2010; 19: 393-398
    PubMedGoogle Scholar
  • 51 Dietrich CF. Characterisation of focal liver lesions with contrast enhanced ultrasonography. Eur J Radiol 2004; 51: 9-17
    CrossrefPubMedGoogle Scholar
  • 52 Dietrich CF, Schreiber-Dietrich D, Schuessler G et al. Contrast enhanced ultrasound of the liver – state of the art. Dtsch Med Wochenschr 2007; 132: 1225-1231
    Article in Thieme ConnectPubMedGoogle Scholar
  • 53 Dietrich CF. Comments and illustrations regarding the guidelines and good clinical practice recommendations for contrast-enhanced ultrasound (CEUS) – update 2008. Ultraschall in Med 2008; 29: S188-S202
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Guang Y, Xie L, Ding H et al. Diagnosis value of focal liver lesions with SonoVue(R)-enhanced ultrasound compared with contrast-enhanced computed tomography and contrast-enhanced MRI: a meta-analysis. J Cancer Res Clin Oncol 2011; 137: 1595-1605
    CrossrefPubMedGoogle Scholar
  • 55 Caturelli E, Bartolucci F, Biasini E et al. Diagnosis of liver nodules observed in chronic liver disease patients during ultrasound screening for early detection of hepatocellular carcinoma. Am J Gastroenterol 2002; 97: 397-405
    CrossrefPubMedGoogle Scholar
  • 56 Sangiovanni A, Manini MA, Iavarone M et al. The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis. Gut 2010; 59: 638-644
    CrossrefPubMedGoogle Scholar
  • 57 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
  • 58 Correas JM, Bridal L, Lesavre A et al. Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts. Eur Radiol 2001; 11: 1316-1328
    CrossrefPubMedGoogle Scholar
  • 59 Wilson SR, Kim TK, Jang HJ et al. Enhancement patterns of focal liver masses: discordance between contrast-enhanced sonography and contrast-enhanced CT and MRI. Am J Roentgenol 2007; 189: W7-W12
    CrossrefPubMedGoogle Scholar
  • 60 Enders J, Zimmermann E, Rief M et al. Reduction of claustrophobia during magnetic resonance imaging: methods and design of the “CLAUSTRO” randomized controlled trial. BMC Med Imaging 2011; 11: 4
    CrossrefPubMedGoogle Scholar
  • 61 Solbiati L, Ierace T, Tonolini M et al. Guidance and monitoring of radiofrequency liver tumor ablation with contrast-enhanced ultrasound. Eur J Radiol 2004; 51: S19-S23
    CrossrefPubMedGoogle Scholar
  • 62 Leen E, Moug SJ, Horgan P. Potential impact and utilization of ultrasound contrast media. Eur Radiol 2004; 14: 16-24
    PubMedGoogle Scholar