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Role of Contrast-Enhanced Ultrasound as a Second-Line Diagnostic Modality in Noninvasive Diagnostic Algorithms for Hepatocellular Carcinoma

  • Hyo-Jin Kang (Department of Radiology, Seoul National University Hospital) ;
  • Jeong Min Lee (Department of Radiology, Seoul National University Hospital) ;
  • Jeong Hee Yoon (Department of Radiology, Seoul National University Hospital) ;
  • Joon Koo Han (Department of Radiology, Seoul National University Hospital)
  • Received : 2020.06.03
  • Accepted : 2020.09.05
  • Published : 2021.03.01

Abstract

Objective: To investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) and its role as a second-line imaging modality after gadoxetate-enhanced MRI (Gd-EOB-MRI) in the diagnosis of hepatocellular carcinoma (HCC) among at risk observations. Materials and Methods: We prospectively enrolled participants at risk of HCC with treatment-naïve solid hepatic observations (≥ 1 cm) of Liver Imaging Reporting and Data System (LR)-3/4/5/M during surveillance and performed Gd-EOB-MRI. A total of one hundred and three participants with 103 hepatic observations (mean size, 28.2 ± 24.5 mm; HCCs [n = 79], non-HCC malignancies [n = 15], benign [n = 9]; diagnosed by pathology [n = 57], or noninvasive method [n = 46]) were included in this study. The participants underwent CEUS with sulfur hexafluoride. Arterial phase hyperenhancement (APHE) and washout on Gd-EOB-MRI and CEUS were evaluated. The distinctive washout in CEUS was defined as mild washout 60 seconds after contrast injection. The diagnostic ability of Gd-EOB-MRI and of CEUS as a second-line modality for HCC were determined according to the European Association for the Study of the Liver (EASL) and the Korean Liver Cancer Association and National Cancer Center (KLCA-NCC) guidelines. The diagnostic abilities of both imaging modalities were compared using the McNemar's test. Results: The sensitivity of CEUS (60.8%) was lower than that of Gd-EOB-MRI (72.2%, p = 0.06 by EASL; 86.1%, p < 0.01 by KLCA-NCC); however, the specificity was 100%. By performing CEUS on the inconclusive observations in Gd-EOB-MRI, HCCs without APHE (n = 10) or washout (n = 12) on Gd-EOB-MRI further presented APHE (80.0%, 8/10) or distinctive washout (66.7%, 8/12) on CEUS, and more HCCs were diagnosed than with Gd-EOB-MRI alone (sensitivity: 72.2% vs. 83.5% by EASL, p < 0.01; 86.1% vs. 91.1% by KCLA-NCC, p = 0.04). There were no false-positive cases for HCC on CEUS. Conclusion: The addition of CEUS to Gd-EOB-MRI as a second-line diagnostic modality increases the frequency of HCC diagnosis without changing the specificities.

Keywords

Acknowledgement

This study was supported by a research grant (no. 0620183430) from Bracco Imaging (Milan, Italy). We thank to Hyun Hee Lee (Seoul National University Hospital, Korea) for her assistant.

References

  1. Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2018;68:723-750  https://doi.org/10.1002/hep.29913
  2. Cruite I, Tang A, Sirlin CB. Imaging-based diagnostic systems for hepatocellular carcinoma. AJR Am J Roentgenol 2013;201:41-55  https://doi.org/10.2214/AJR.13.10570
  3. Tang A, Cruite I, Sirlin CB. Toward a standardized system for hepatocellular carcinoma diagnosis using computed tomography and MRI. Expert Rev Gastroenterol Hepatol 2013;7:269-279  https://doi.org/10.1586/egh.13.3
  4. Tang A, Cruite I, Mitchell DG, Sirlin CB. Hepatocellular carcinoma imaging systems: why they exist, how they have evolved, and how they differ. Abdom Radiol (NY) 2018;43:3-12  https://doi.org/10.1007/s00261-017-1292-3
  5. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol 2018;69:182-236  https://doi.org/10.1016/j.jhep.2018.03.019
  6. Korean Liver Cancer Association, National Cancer Center. 2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the management of hepatocellular carcinoma. Korean J Radiol 2019;20:1042-1113  https://doi.org/10.3348/kjr.2019.0140
  7. Claudon M, Dietrich CF, Choi BI, Cosgrove DO, Kudo M, Nolsoe CP, 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 Med 2013;34:11-29 
  8. Aube C, Oberti F, Lonjon J, Pageaux G, Seror O, N'Kontchou G, et al. EASL and AASLD recommendations for the diagnosis of HCC to the test of daily practice. Liver Int 2017;37:1515-1525  https://doi.org/10.1111/liv.13429
  9. Strobel D, Bernatik T, Blank W, Schuler A, Greis C, Dietrich CF, 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 Med 2011;32:593-597  https://doi.org/10.1055/s-0031-1271114
  10. Kim TK, Noh SY, Wilson SR, Kono Y, Piscaglia F, Jang HJ, et al. Contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) 2017-a review of important differences compared to the CT/MRI system. Clin Mol Hepatol 2017;23:280-289  https://doi.org/10.3350/cmh.2017.0037
  11. Kang HJ, Kim JH, Joo I, Han JK. Additional value of contrast-enhanced ultrasound (CEUS) on arterial phase non-hyperenhancement observations (≥ 2 cm) of CT/MRI for high-risk patients: focusing on the CT/MRI LI-RADS categories LR-3 and LR-4. Abdom Radiol (NY) 2020;45:55-63  https://doi.org/10.1007/s00261-019-02132-x
  12. Itai Y, Furui S, Ohtomo K, Kokubo T, Yamauchi T, Minami M, et al. Dynamic CT features of arterioportal shunts in hepatocellular carcinoma. AJR Am J Roentgenol 1986;146:723-727  https://doi.org/10.2214/ajr.146.4.723
  13. Maruyama H, Takahashi M, Ishibashi H, Yoshikawa M, Yokosuka O. Contrast-enhanced ultrasound for characterisation of hepatic lesions appearing non-hypervascular on CT in chronic liver diseases. Br J Radiol 2012;85:351-357  https://doi.org/10.1259/bjr/20440141
  14. Yu JS, Kim KW, Jeong MG, Lee JT, Yoo HS. Nontumorous hepatic arterial-portal venous shunts: MR imaging findings. Radiology 2000;217:750-756  https://doi.org/10.1148/radiology.217.3.r00dc13750
  15. Jang HJ, Kim TK, Wilson SR. Small nodules (1-2 cm) in liver cirrhosis: characterization with contrast-enhanced ultrasound. Eur J Radiol 2009;72:418-424  https://doi.org/10.1016/j.ejrad.2008.08.011
  16. Leoni S, Piscaglia F, Granito A, Borghi A, Galassi M, Marinelli S, et al. Characterization of primary and recurrent nodules in liver cirrhosis using contrast-enhanced ultrasound: which vascular criteria should be adopted? Ultraschall Med 2013;34:280-287  https://doi.org/10.1055/s-0033-1335024
  17. Vilana R, Forner A, Bianchi L, Garcia-Criado A, Rimola J, de Lope CR, 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  https://doi.org/10.1002/hep.23600
  18. Li R, Zhang X, Ma KS, Li XW, Xia F, Zhong H, et al. Dynamic enhancing vascular pattern of intrahepatic peripheral cholangiocarcinoma on contrast-enhanced ultrasound: the influence of chronic hepatitis and cirrhosis. Abdom Imaging 2013;38:112-119  https://doi.org/10.1007/s00261-012-9854-x
  19. Chen LD, Xu HX, Xie XY, Xie XH, Xu ZF, Liu GJ, et al. Intrahepatic cholangiocarcinoma and hepatocellular carcinoma: differential diagnosis with contrast-enhanced ultrasound. Eur Radiol 2010;20:743-753  https://doi.org/10.1007/s00330-009-1599-8
  20. Wildner D, Bernatik T, Greis C, Seitz K, Neurath MF, Strobel D. CEUS in hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma in 320 patients - early or late washout matters: a subanalysis of the DEGUM multicenter trial. Ultraschall Med 2015;36:132-139  https://doi.org/10.1055/s-0034-1399147
  21. Wildner D, Pfeifer L, Goertz RS, Bernatik T, Sturm J, Neurath MF, et al. Dynamic contrast-enhanced ultrasound (DCE-US) for the characterization of hepatocellular carcinoma and cholangiocellular carcinoma. Ultraschall Med 2014;35:522-527  https://doi.org/10.1055/s-0034-1385170
  22. Kono Y, Lyshchik A, Cosgrove D, Dietrich CF, Jang HJ, Kim TK, 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 Med 2017;38:85-86  https://doi.org/10.1055/s-0042-124369
  23. Piscaglia F, Kudo M, Han KH, Sirlin C. Diagnosis of hepatocellular carcinoma with non-invasive imaging: a plea for worldwide adoption of standard and precise terminology for describing enhancement criteria. Ultraschall Med 2017;38:9-11  https://doi.org/10.1055/s-0042-124204
  24. Terzi E, Iavarone M, Pompili M, Veronese L, Cabibbo G, Fraquelli M, et al. Contrast ultrasound LI-RADS LR-5 identifies hepatocellular carcinoma in cirrhosis in a multicenter restropective study of 1006 nodules. J Hepatol 2018;68:485-492  https://doi.org/10.1016/j.jhep.2017.11.007
  25. Chernyak V, Fowler KJ, Kamaya A, Kielar AZ, Elsayes KM, Bashir MR, et al. Liver Imaging Reporting and Data System (LI-RADS) version 2018: imaging of hepatocellular carcinoma in at-risk patients. Radiology 2018;289:816-830  https://doi.org/10.1148/radiol.2018181494
  26. Foucher J, Chanteloup E, Vergniol J, Castera L, Le Bail B, Adhoute X, et al. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut 2006;55:403-408  https://doi.org/10.1136/gut.2005.069153
  27. Lim JK, Flamm SL, Singh S, Falck-Ytter YT; Clinical Guidelines Committee of the American Gastroenterological Association. American Gastroenterological Association Institute Guideline on the role of elastography in the evaluation of liver fibrosis. Gastroenterology 2017;152:1536-1543  https://doi.org/10.1053/j.gastro.2017.03.017
  28. Kang HJ, Lee JM, Jeon SK, Ryu H, Yoo J, Lee JK, et al. Microvascular flow imaging of residual or recurrent hepatocellular carcinoma after transarterial chemoembolization: comparison with color/power Doppler imaging. Korean J Radiol 2019;20:1114-1123  https://doi.org/10.3348/kjr.2018.0932
  29. Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 2017;11:317-370  https://doi.org/10.1007/s12072-017-9799-9
  30. Jang HJ, Kim TK, Burns PN, Wilson SR. CEUS: an essential component in a multimodality approach to small nodules in patients at high-risk for hepatocellular carcinoma. Eur J Radiol 2015;84:1623-1635  https://doi.org/10.1016/j.ejrad.2015.05.020
  31. Bolondi L, Gaiani S, Celli N, Golfieri R, Grigioni WF, Leoni S, et al. Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma. Hepatology 2005;42:27-34  https://doi.org/10.1002/hep.20728
  32. Khalili K, Kim TK, Jang HJ, Haider MA, Khan L, Guindi M, et al. Optimization of imaging diagnosis of 1-2 cm hepatocellular carcinoma: an analysis of diagnostic performance and resource utilization. J Hepatol 2011;54:723-728  https://doi.org/10.1016/j.jhep.2010.07.025
  33. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358-380  https://doi.org/10.1002/hep.29086
  34. Kim TH, Yoon JH, Lee JM. Emerging role of hepatobiliary magnetic resonance contrast media and contrast-enhanced ultrasound for noninvasive diagnosis of hepatocellular carcinoma: emphasis on recent updates in major guidelines. Korean J Radiol 2019;20:863-879 https://doi.org/10.3348/kjr.2018.0450