Ultraschall Med 2016; 37(06): 627-634
DOI: 10.1055/s-0042-112221
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

LI-RADS-CEUS – Proposal for a Contrast-Enhanced Ultrasound Algorithm for the Diagnosis of Hepatocellular Carcinoma in High-Risk Populations

LI-RADS-CEUS mit kontrastverstärktem Ultraschall – Vorschlag für eine standardisierte Klassifikation HCC-suspekter Leberraumforderungen bei Risikopatienten
B. Schellhaas
Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
,
D. Wildner
Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
,
L. Pfeifer
Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
,
R. S. Goertz
Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
,
A. Hagel
Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
,
M. F. Neurath
Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
,
D. Strobel
Department of Internal Medicine 1, University Hospital Erlangen, Erlangen, Germany
› Author Affiliations
Further Information

Publication History

13 April 2016

05 July 2016

Publication Date:
03 August 2016 (online)

Abstract

Purpose: To develop a contrast-enhanced ultrasound algorithm (LI-RADS-CEUS = liver imaging reporting and data system with contrast-enhanced ultrasound) for the diagnosis of hepatocellular carcinoma (HCC) in patients at risk.

Materials and Methods: A CEUS algorithm (LI-RADS-CEUS) was designed analogously to CT- and MRI-based LI-RADS. LI-RADS-CEUS was evaluated retrospectively in 50 patients at risk with confirmed HCC or non-HCC lesions (test group) with subsequent validation in a prospective cohort of 50 patients (validation group). Results were compared to histology, CE-CT and CE-MRI as reference standards.

Results: Tumor diagnosis in the test group/validation group (n = 50/50) were 46/41 HCCs, 3/3 intrahepatic cholangiocellular carcinomas (ICCs) and 1/6 benign lesions. The diagnostic accuracy of LI-RADS-CEUS for HCC, ICC and non-HCC-non-ICC-lesions was 89 %. For the diagnosis of HCC, the diagnostic accuracy was 93.5 % (43/46 cases) in the test group and 95.1 % (39/41 cases) in the validation group. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 94.3 %, 66.6 %, 94.3 % and 66.6 %, respectively (mean values from both cohorts). Histological findings of HCC were available in 40 versus 23 cases (in total: G1 / G2/G3: 15/35/13). Arterial hyperenhancement was seen in 68/87 (78.2 %) of HCCs. Arterial hyperenhancement with subsequent portal venous or late phase hypoenhancement was seen in 66 % of HCCs.

Conclusion: LI-RADS-CEUS offers a CEUS algorithm for standardized assessment and reporting of focal liver lesions in patients at risk for HCC. Arterial hyperenhancement in CEUS is the key feature for the diagnosis of HCC in patients at risk, whereas washout is not a necessary prerequisite.

Zusammenfassung

Ziel: Entwicklung eines standardisierten Kontrastmittel-Ultraschall-(CEUS-)basierten Algorithmus (LI-RADS-CEUS) für die Diagnostik hepatozellulärer Karzinome (HCCs) bei Risikopatienten.

Material und Methoden: Ein CEUS-basierter Algorithmus (LI-RADS-CEUS) wurde analog zum CT- und MRT-basierten LI-RADS (Liver Imaging Reporting and Data System) entwickelt. LI-RADS-CEUS wurde retrospektiv an 50 Risikopatienten mit gesicherten HCC- oder Nicht-HCC-Läsionen getestet (Testgruppe) und anschließend prospektiv bei 50 Risikopatienten validiert (Validierungsgruppe). Als Referenz dienten Histologie, CT und MRT.

Ergebnisse: In beiden Patientenkohorten (n = 50/50) fanden sich 46/41 HCCs, 3/3 intrahepatische cholangiozelluläre Karzinome (ICCs) und 1/6 benigne Leberläsionen. Die diagnostische Genauigkeit von LI-RADS-CEUS für HCC, ICC und Nicht- HCC-/-ICC-Herde betrug insgesamt 89 %. Für HCCs war die diagnostische Genauigkeit in den Gruppen 93,5 % (43/46 HCCs)/95,1 % (39/41 HCCs). Sensitivität, Spezifität, PPW und NPW für HCCs betrugen 94,3 %/66,6 %/94,3 % und 66,6 % (Mittelwerte beider Patientenkohorten). Bei 40/23 HCCs lag eine Histologie vor (insgesamt: G1/G2/G3: 15/35/13). Arterielles Hyperenhancement fand sich bei 68/87 (78,2%) der HCCs. Arterielles Hyperenhancement mit anschließendem portalvenösem oder Spätphasen-Hypoenhancement fand sich bei 66% der HCCs.

Schlussfolgerung: LI-RADS-CEUS bietet einen CEUS-Algorithmus für die standardisierte Beurteilung und Dokumentation HCC-suspekter Läsionen bei Risikopatienten. Arterielles Hyperenhancement ist der wichtigste Parameter in CEUS für die Diagnose eines HCC; Washout ist keine zwingende Voraussetzung.

 
  • References

  • 1 Westwood M, Joore M, Grutters J et al. Contrast-enhanced ultrasound using SonoVue® (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
  • 2 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
  • 3 Bota S, Piscaglia F, Marinelli S et al. Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma. Liver Cancer 2012; 1: 190-200
  • 4 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
  • 5 Bellissimo F, Pinzone MR, Cacopardo B et al. Diagnostic and therapeutic management of hepatocellular carcinoma. World J Gastroenterol 2015; 21: 12003-12021
  • 6 Bruix J, Sherman M. American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020-1022
  • 7 S 3- Leitlinie Deutschland: AWMF-Leitlinie “Hepatozelluläres Karzinom”, Registernummer 032 – 053OL, Stand: 01.05.2013, gültig bis 31.05.2016. http://www.awmf.org/leitlinien/detail/ll/032-053OL.html
  • 8 Piscaglia F, Iavarone M, Galassi M et al. Cholangiocarcinoma in Cirrhosis: Value of Hepatocyte Specific Magnetic Resonance Imaging. Dig Dis 2015; 33: 735-744
  • 9 European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012; 56: 908-943
  • 10 Italian Association for the Study of the Liver (AISF); AISF Expert Panel; AISF Coordinating Committee. Position paper of the Italian Association for the Study of the Liver (AISF): the multidisciplinary clinical approach to hepatocellular carcinoma. Dig Liver Dis 2013; 45: 712-723
  • 11 Kokudo N, Hasegawa K, Akahane M et al. Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol Res 2015; 45 DOI: 10.1111/hepr.12464.
  • 12 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
  • 13 Leoni S, Piscaglia F, Granito A et al. Characterization of primary and recurrent nodules in liver cirrhosis using contrast-enhanced ultrasound: which vascular criteria should be adopted?. Ultraschall in Med 2013; 34: 280-287
  • 14 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
  • 15 Choi BI, Lee JM, Kim TK et al. Diagnosing Borderline Hepatic Nodules in Hepatocarcinogenesis: Imaging Performance. Am J Roentgenol 2015; 205: 10-21
  • 16 Shah S, Shukla A, Paunipagar B. Radiological features of hepatocellular carcinoma. J Clin Exp Hepatol 2014; 4 (Suppl. 03) S63-S66
  • 17 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
  • 18 Kim TK, Jang HJ. Contrast-enhanced ultrasound in the diagnosis of nodules in liver cirrhosis. World J Gastroenterol 2014; 20: 3590-3596
  • 19 Mitchell DG, Bruix J, Sherman M et al. LI-RADS (Liver Imaging Reporting and Data System): summary, discussion, and consensus of the LI-RADS Management Working Group and future directions. Hepatology 2015; 61: 1056-1065
  • 20 Tang A, Valasek MA, Sirlin CB. Update on the Liver Imaging Reporting and Data System: What the Pathologist Needs to Know. Adv Anat Pathol 2015; 22: 314-322
  • 21 Seitz K, Piscaglia F. Ultrasound: the only "one stop shop" for modern management of liver disease. Ultraschall in Med 2013; 34: 500-503
  • 22 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
  • 23 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
  • 24 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
  • 25 D'Onofrio M, Crosara S, De Robertis R et al. Contrast-Enhanced Ultrasound of Focal Liver Lesions. Am J Roentgenol 2015; 205: W56-W66
  • 26 Wildner D, Bernatik T, Greis C et al. CEUS in Hepatocellular Carcinoma and Intrahepatic Cholangiocellular Carcinoma in 320 Patients – Early or Late Washout Matters: A Subanalysis of the DEGUM Multicenter Trial. Ultraschall in Med 2015; 36: 132-139
  • 27 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: 522-577
  • 28 McEvoy SH, McCarthy CJ, Lavelle LP et al. Hepatocellular carcinoma: illustrated guide to systematic radiologic diagnosis and staging according to guidelines of the American Association for the Study of Liver Diseases. Radiographics 2013; 33: 1653-1668
  • 29 Darnell A, Forner A, Rimola J et al. Liver Imaging Reporting and Data System with MR Imaging: Evaluation in Nodules 20 mm or Smaller Detected in Cirrhosis at Screening US. Radiology 2015; 275: 698-707
  • 30 Egger C, Goertz RS, Strobel D et al. Dynamic contrast-enhanced ultrasound (DCE-US) for easy and rapid evaluation of hepatocellular carcinoma compared to dynamic contrast-enhanced computed tomography (DCE-CT)--a pilot study. Ultraschall in Med 2012; 33: 587-592
  • 31 Beyer LP, Pregler B, Wiesinger I et al. Continuous dynamic registration of microvascularization of liver tumors with contrast-enhanced ultrasound. Radiol Res Pract 2014; 2014: 347416
  • 32 Knieling F, Waldner MJ, Goertz RS et al. Early response to anti-tumoral treatment in hepatocellular carcinoma--can quantitative contrast-enhanced ultrasound predict outcome?. Ultraschall in Med 2013; 34: 38-46
  • 33 Wobser H, Wiest R, Salzberger B et al. Evaluation of treatment response after chemoembolisation (TACE) in hepatocellular carcinoma using real time image fusion of contrast-enhanced ultrasound (CEUS) and computed tomography (CT)--preliminary results. Clin Hemorheol Microcirc 2014; 57: 191-201
  • 34 Lassau N, Koscielny S, Chami L et al. Advanced hepatocellular carcinoma: early evaluation of response to bevacizumab therapy at dynamic contrast-enhanced US with quantification--preliminary results. Radiology 2011; 258: 291-300 . doi: 10.1148/radiol.10091870. Epub 2010 Oct 27