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Ultraschall Med 2021; 42(02): 120-124
DOI: 10.1055/a-1347-1388
Editorial

Using contrast-enhanced ultrasound in the diagnosis of hepatocellular carcinoma – what we have and have not achieved

Kontrastmittelsonografie in der Diagnostik des hepatozellulären Karzinoms – was wir erreicht haben und was nicht
Deike Strobel
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The initial applications of contrast-enhanced ultrasound to the diagnosis of liver tumors were employed more than 30 years ago in Germany. Initially intended for enhanced imaging of liver metastases, contrast-enhanced ultrasonography evolved into an ideal technique for characterizing focal liver lesions. The introduction of stable contrast agents (SonoVue) and low-MI imaging technology in 2001 marked the breakthrough for widespread clinical use in Europe. Important pioneering work by individual research groups on contrast-enhanced sonographic tumor vascularization patterns was followed in 2008 by the first prospective DEGUM multicenter study with 1349 patients, which demonstrated a greater than 90 % diagnostic accuracy of contrast-enhanced sonography when differentiating B-scan-morphologically unclear hepatic lesions compared to histologically-verified masses [1] [2] [3]. Numerous European multicenter studies have confirmed the high diagnostic value of contrast-enhanced ultrasonography, also in comparison to CT and MRI [4] [5] [6] [7]. Meta-analyses followed, including that of M. Friedrich-Rust in 2013, which demonstrated excellent diagnostic accuracy of contrast-enhanced sonography in differentiating benign and malignant liver lesions in 7231 focal liver lesions, with a sensitivity of 93 % (range 91–95 %) and a specificity of 90 % (range 88–93 %) [8]. The high value of contrast-enhanced sonography was shown when compared to MRT and CT, and also with respect to small hepatic lesions as a problem solver in focal findings which due to their tiny size cannot be classified with certainty using CT or MRI [9]. Contrast-enhanced sonography rightly occupies a firm position in liver tumor diagnostics [10] [11]. It is a cost-effective method, safe to use, and for many patients shortens the path through diagnostic processes [12] [13].



Publication History

Article published online:
12 April 2021

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  • References

  • 1 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
  • 2 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. PMID: 22161557
    Google Scholar
  • 3 Strobel D, Seitz K, Blank W. et al Tumor-specific vascularization pattern of liver me-tastasis, hepatocellular carcinoma, hemangioma and focal nodular hyperplasia in the differential diagnosis of 1,349 liver lesions in contrast-en-hanced ultrasound (CEUS). Ultraschall in Med 2009; 30 (04) 376-382 . https://doi.org/10.1055/s-0028-1109672
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Tranquart F, Le Gouge A, Correas JM. et al Role of contrast-enhanced ultrasound in the blinded assessment of focal liver lesions in comparison with MDCT and CEMRI: results from a multicentre clinical trial. Eur J Cancer Suppl 2008; 6: 9-15
    CrossrefPubMedGoogle Scholar
  • 5 Trillaud H, Bruel JM, Valaette 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 . doi:10.3748/wjg.15.3748
    CrossrefPubMedGoogle Scholar
  • 6 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 . doi:10.1055/s-0033-1355728. Epub 2014 Feb 21
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Sporea I, Săndulescu DL, Şirli R. et al Contrast-Enhanced Ultrasound for the Characterization of Malignant versus Benign Focal Liver Lesions in a Prospective Multicenter Experience - The SRUMB Study. J Gastrointestin Liver Dis 2019; 28: 191-196 . doi:10.15403/jgld-180
    CrossrefPubMedGoogle Scholar
  • 8 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
  • 9 Xie L, Guang Y, Ding H. et al Diagnostic value of contrast-enhanced ultrasound, computed tomography and magnetic resonance imaging for focal liver lesions: a meta-analysis. Ultrasound Med Biol 2011; 37: 854-861
    CrossrefPubMedGoogle Scholar
  • 10 Dietrich CF, Nolsøe CP, Barr RG. et al Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver – Update 2020 – WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS. Ultraschall in Med 2020; 41: 562-585 . doi:10.1055/a-1177-0530. Epub 2020 Jul 24
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of benign liver tumours. J Hepatol 2016; 65: 386-398
    CrossrefPubMedGoogle Scholar
  • 12 Piscaglia F, Bolondi L. Italian Society for Ultra-sound in Medicine and Biology (SIUMB) Study Group on Ultrasound Contrast Agents. The safety of Sonovue in abdominal applications: retrospective analysis of 23188 investigations. Ultrasound Med Biol 2006; 32: 1369-1375
    CrossrefPubMedGoogle Scholar
  • 13 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. PMID: 23611316 Free PMC article. Review
    Google Scholar
  • 14 Niu Y, Huang T, Lian F. et al Contrast-enhanced ultrasonography for the diagnosis of small hepatocellular carcinoma: a meta-analysis and meta-regression analysis. Tumour Biol 2013; 34: 3667-3674
    CrossrefPubMedGoogle Scholar
  • 15 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
  • 16 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Marrero JA, Kulik LM, Sirlin CB. et al Diagnosis, Staging, and Management of HepatocellularCarcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2018; 68: 723-750
    Google Scholar
  • 18 Omata M, Cheng AL, Kokudo N. et al Asia-Pacific clinical practice guidelineson the management of hepatocellularcarcinoma: a 2017 update. Hepatol Int 2017; 11: 317-370
    CrossrefPubMedGoogle Scholar
  • 19 Foerster F, Galle RP. Comparison of the current international guidelines on the management of HCC. JHEP Rep 2019; 1: 114-119
    CrossrefPubMedGoogle Scholar
  • 20 Galle PR, Forner A, Llovet JM. et al EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018; 69: 182-236
    CrossrefPubMedGoogle Scholar
  • 21 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
  • 22 Schellhaas B, Strobel D. Tips and Tricks in Contrast-Enhanced Ultrasound (CEUS) for the Characterization andDetection of Liver Malignancies. Ultraschall in Med 2019; 40: 404-424
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Kono Y, Lyshchik A, Cosgrove D. et al Contrast enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS®): the official version by the American College of radiology (ACR). Ultraschall in der Medizin-European Journal of Ultrasound 2017; 38: 85-86
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Wilson SR, Lyshchik A, Piscaglia F. et al CEUS LI-RADS: algorithm, implementation, and key differences from CT/MRI. Abdom Radiol (NY) 2018; 43: 127-142
    CrossrefPubMedGoogle Scholar
  • 25 Piscaglia F, Wilson SR, Andrej Lyshchik A. et al American College of Radiology Contrast Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) for the diagnosis of Hepatocellular Carcinoma: a pictorial essay. Ultraschall in Med 2017; 38: 320-324
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Li J, Yang L, Ma L. et al Diagnostic Accuracy of Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) for Differentiating Between Hepatocellular Carcinoma and Other Hepatic Malignancies in High-Risk Patients: A Meta-Analysis. Ultraschall in Med [Online ahead of print]
    Google Scholar
  • 27 Schellhaas B, Görtz RS, Pfeifer L. et al Diagnostic accuracy of contrast-enhanced ultrasound for the differential diagnosis of hepatocellular carcinoma: ESCULAP versus CEUS-LI-RADS. Eur J Gastroenterol Hepatol 2017; 29: 1036-1044
    CrossrefPubMedGoogle Scholar
  • 28 Schellhaas B, Pfeifer L, Kielisch C. et al Interobserver Agreement for Contrast-Enhanced Ultrasound (CEUS)-Based Standardized Algorithms for the Diagnosis of Hepatocellular Carcinoma in High-Risk Patients. Ultraschall in Med 2018; 39: 667-674
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Schellhaas B, Hammon M, Strobel D. et al Interobserver and intermodality agreement of standardized algorithms for non-invasive diagnosis of hepatocellular carcinoma in high-risk patients: CEUS-LI-RADS versus MRI-LI-RADS. Eur Radiol 2018; 28: 4254-4264
    CrossrefPubMedGoogle Scholar
  • 30 Schellhaas B, Bernatik T, Bohle W. et al Contrast-Enhanced Ultrasound Algorithms (CEUS-LIRADS/ESCULAP) for the Noninvasive Diagnosis of Hepatocellular Carcinoma - A Prospective Multicenter DEGUM Study. Ultraschall in Med 2020; DOI: 10.1055/a-1198-4874.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Pfeifer L, Zopf S, Siebler J. et al Prospective Evaluation of Acoustic Radiation Force Impulse (ARFI) Elastography and High-Frequency B-Mode Ultrasound in Compensated Patients for the Diagnosis of Liver Fibrosis/Cirrhosis in Comparison to Mini-Laparoscopic Biopsy. Ultraschall in Med 2015; 36: 581-589
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Cantisani V, Bertolotto M, Clevert DA. et al EFSUMB 2020 Proposal for a Contrast-Enhanced Ultrasound-Adapted Bosniak Cyst Categorization – Position Statement. Ultraschall in Med 2020; DOI: 10.1055/a-1300-1727. [Online ahead of print]
    Article in Thieme ConnectPubMedGoogle Scholar