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Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma

  • Hepatobiliary-Pancreas
  • Published:
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Abstract

Objective

Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs.

Methods

A total of 85 surgically resected nodules (≤30 mm) were analyzed.

HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared.

Results

Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95 % confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682–0.890): CEUS, 0.784 (0.679–0.889), in combination, 0.876 (0.792–0.959). The sensitivity, specificity, and accuracy were 64.1 %, 95.7 %, and 81.2 % in EOB-MRI, 56.4 %, 97.8 %, and 78.8 % in CEUS, and 84.6 %, 95.7 %, and 90.6 % in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS.

Conclusion

Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs.

Key Points

• Non-SN has a higher frequency of MVI and intrahepatic metastasis than SN.

• Macroscopic classification is useful to choose the treatment strategy for small HCCs.

• Diagnostic ability for macroscopic findings of EOB-MRI and CEUS were statistically equal.

• The diagnosis of macroscopic findings by individual modality has limitations.

• Combined diagnosis of EOB-MRI and CEUS provides high diagnostic ability.

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Abbreviations

AFP:

Alpha-fetoprotein

AP:

Arterial-phase

AUROC:

Area under the receiver operating characteristic curve

CECT:

Contrast-enhanced computed tomography

CEUS:

Contrast-enhanced ultrasound

CMN:

Confluent multinodular type

DCP:

Des-γ-carboxyprothrombin

EOB-MRI:

Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging

Gd-EOB-DTPA:

Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid

HBP:

Hepatobiliary phase

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

ICG R15:

Indocyanine green retention rate at 15 minutes

IF:

Infiltrative type

MVI:

Microvascular invasion

NBNC:

Patients negative for both HBs antigen and HCV antibody

NPV:

Negative predictive value

PPV:

Positive predictive value

PVP:

Portal venous-phase

ROC:

Receiver operating characteristic

SN:

Simple nodular

SN-DM:

Simple nodular type with distinct margin

SN-EG:

Simple nodular type with extranodular growth

SN-IN:

Small nodular type with indistinct margin

US:

Ultrasound

References

  1. Shimada K, Sakamoto Y, Esaki M et al (2007) Analysis of prognostic factors affecting survival after initial recurrence and treatment efficacy for recurrence in patients undergoing potentially curative hepatectomy for hepatocellular carcinoma. Ann Surg Oncol 14:2337–2347

    Article  PubMed  Google Scholar 

  2. Shah SA, Cleary SP, Wei AC et al (2007) Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery 141:330–339

    Article  PubMed  Google Scholar 

  3. Dupont-Bierre E, Compagnon P, Raoul JL, Fayet G, de Lajarte-Thirouard AS, Boudjema K (2005) Resection of hepatocellular carcinoma in non-cirrhotic liver: analysis of risk factors for survival. J Am Coll Surg 201:663–670

    Article  PubMed  Google Scholar 

  4. Kaibori M, Ishizaki M, Saito T, Matsui K, Kwon AH, Kamiyama Y (2009) Risk factors and outcome of early recurrence after resection of small hepatocellular carcinomas. Am J Surg 198:39–45

    Article  PubMed  Google Scholar 

  5. Kanai T, Hirohashi S, Upton MP et al (1987) Pathology of small hepatocellular carcinoma: a proposal for a new gross classification. Cancer 60:810–819

    Article  CAS  PubMed  Google Scholar 

  6. Nakashima Y, Nakashima O, Tanaka M, Okuda K, Nakashima M, Kojiro M (2003) Portal vein invasion and intrahepatic micrometastasis in small hepatocellular carcinoma by gross type. Hepatol Res 26:142–147

    Article  PubMed  Google Scholar 

  7. Hui AM, Takayama T, Sano K et al (2000) Predictive value of gross classification of hepatocellular carcinoma on recurrence and survival after hepatectomy. J Hepatol 33:975–979

    Article  CAS  PubMed  Google Scholar 

  8. Sumie S, Kuromatsu R, Okuda K et al (2008) Microvascular invasion in patients with hepatocellular carcinoma and its predictable clinicopathological factors. Ann Surg Oncol 15:1375–1382

    Article  PubMed  Google Scholar 

  9. Ueno S, Kudo F, Sakoda M et al (2008) Efficacy of anatomic resection vs nonanatomic resection for small nodular hepatocellular carcinoma based on gross classification. J Hepatobiliary Pancreat Surg 15:493–500

    Article  PubMed  Google Scholar 

  10. Ariizumi S, Kitagawa K, Kotera Y et al (2011) A non-smooth tumor margin in the hepatobiliary phase of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging predicts microscopic portal vein invasion, intrahepatic metastasis, and early recurrence after hepatectomy in patients with hepatocellular carcinoma. J Hepatobiliary Pancreat Sci 18:575–585

    Article  PubMed  Google Scholar 

  11. Tsujita E, Yamashita Y, Takeishi K et al (2013) The clinicopathological impact of gross classification on solitary small hepatocellular carcinoma. Hepatogastroenterology 60:1726–1730

    PubMed  Google Scholar 

  12. Vogl TJ, Kümmel S, Hammerstingl R et al (1996) Liver tumors: comparison of MR imaging with Gd-EOB-DTPA and Gd-DTPA. Radiology 200:59–67

    Article  CAS  PubMed  Google Scholar 

  13. Huppertz A, Balzer T, Blakeborough A et al (2004) Improved detection of focal liver lesions at MR imaging: multicenter comparison of gadoxetic acid-enhanced MR images with intraoperative findings. Radiology 230:266–275

    Article  PubMed  Google Scholar 

  14. Huppertz A, Haraida S, Kraus A et al (2005) Enhancement of focal liver lesions at gadoxetic acid-enhanced MR imaging: correlation with histopathologic findings and spiral CT-initial observations. Radiology 234:468–478

    Article  PubMed  Google Scholar 

  15. Saito K, Kotake F, Ito N et al (2005) Gd-EOB-DTPA-enhanced MRI for hepatocellular carcinoma: quantitative evaluation of tumor enhancement in hepatobiliary phase. Magn Reson Med Sci 4:1–9

    Article  PubMed  Google Scholar 

  16. Bluemke DA, Sahani D, Amendola M et al (2005) Efficacy and safety of MR imaging with liver-specific contrast agent: U.S. multicenter phase III study. Radiology 237:89–98

    Article  PubMed  Google Scholar 

  17. Hammerstingl R, Huppertz A, Breuer J et al (2008) Diagnostic efficacy of gadoxetic acid (Primovist) –enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions. Eur Radiol 18:457–467

    Article  PubMed  Google Scholar 

  18. Solbiati L, Tonolini M, Cova L, Goldberg SN (2001) The role of contrast-enhanced ultrasound in the detection of focal liver leasions. Eur Radiol 11:E15–E26

    Article  PubMed  Google Scholar 

  19. Konopke R, Bunk A, Kersting S (2007) The role of contrast-enhanced ultrasound for focal liver lesion detection: an overview. Ultrasound Med Biol 33:1515–1526

    Article  CAS  PubMed  Google Scholar 

  20. Yanagisawa K, Moriyasu F, Miyahara T, Yuki M, Iijima H (2007) Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells. Ultrasound Med Biol 33:318–325

    Article  PubMed  Google Scholar 

  21. Korenaga K, Korenaga M, Furukawa M, Yamasaki T, Sakaida I (2009) Usefulness of sonazoid contrast-enhanced ultrasonography for hepatocellular carcinoma: comparison with pathological diagnosis and superparamagnetic iron oxide magnetic resonance images. J Gastroenterol 44:733–741

    Article  PubMed  Google Scholar 

  22. Granito A, Galassi A, Piscaglia F et al (2013) Impact of gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance on the non-invasive diagnosis of small hepatocellular carcinoma: a prospective study. Aliment Pharmacol Ther 37:355–363

    Article  CAS  PubMed  Google Scholar 

  23. Mita K, Kim SR, Kudo M et al (2010) Diagnostic sensitivity of imaging modalities for hepatocellular carcinoma smaller than 2 cm. World J Gastroenterol 16:4187–4192

    Article  PubMed Central  PubMed  Google Scholar 

  24. Hatanaka K, Minami Y, Kudo M, Inoue T, Chung H, Haji S (2014) The gross classification of hepatocellular carcinoma: usefulness of contrast-enhanced US. J Clin Ultrasound 42:1–8

    Article  PubMed  Google Scholar 

  25. Tada T, Kumada T, Toyoda H et al (2014) Diagnostic accuracy for macroscopic classification of nodular hepatocellular carcinoma: comparison of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and angiography-assisted computed tomography. J Gastroenterol. doi:10.1007/s00535-014-0947-x

    PubMed Central  Google Scholar 

  26. Fujinaga Y, Kadoya M, Kozaka K et al (2013) Prediction of macroscopic findings of hepatocellular carcinoma on hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging: Correlation with pathology. Hepatol Res 43:488–494

    Article  CAS  PubMed  Google Scholar 

  27. Tada T, Kumada T, Toyoda H et al (2014) Utility of contrast-enhanced ultrasound with perflubutane for diagnosing the macroscopic type of small nodular hepatocellular carcinoma. Eur Radiol 24:2157–2166

    Article  PubMed  Google Scholar 

  28. Liver Cancer Study Group of Japan (2010) General rules for the clinical and pathological study of primary liver cancer, 3rd English edn. Kanehara, Tokyo, pp 17–18

    Google Scholar 

  29. Akobeng AK (2007) Understanding diagnostic tests 3: receiver operating characteristic curves. Acta Paediatr 96:644–647

    Article  PubMed  Google Scholar 

  30. Swets JA (1988) Measuring the accuracy of diagnostic systems. Science 240:1285–1293

    Article  CAS  PubMed  Google Scholar 

  31. Kundel HL, Polansky M (2003) Measurement of observer agreement. Radiology 228:303–308

    Article  PubMed  Google Scholar 

  32. Kudo M, Hatanaka K, Maekawa K (2008) Defect reperfusion imaging, a newly developed novel technology using Sonazoid in treatment of hepatocellular carcinoma. J Med Ultrasound 16:169–176

    Article  Google Scholar 

  33. Hatanaka K, Kudo M, Minami Y et al (2008) Differential diagnosis of hepatic tumors: value of contrast-enhanced harmonic sonography using the newly developed contrast agent, Sonazoid. Intervirology 51:61–69

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The scientific guarantor of this publication is Kazuaki Chayama, M.D., Ph.D. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article: the MRI and CEUS contrast agents used in the present study were not provided/sponsored by the industry. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Institutional review board approval and written informed consent were not required because this study is a retrospective analysis of EOB-MRI and CEUS, obtained for clinical purposes. Methodology: retrospective, diagnostic or prognostic study / observational, performed at one institution#.

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Authors and Affiliations

  1. Department of Gastroenterology and Metabolism, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Tomoki Kobayashi, Hiroshi Aikata, Masahiro Hatooka, Kei Morio, Reona Morio, Hiromi Kan, Hatsue Fujino, Takayuki Fukuhara, Keiichi Masaki, Atsushi Ohno, Noriaki Naeshiro, Takashi Nakahara, Yohji Honda, Eisuke Murakami, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Yoshiiku Kawakami, Hideyuki Hyogo, Shoichi Takahashi & Kazuaki Chayama

  2. Liver Research Project Center, Hiroshima University, Hiroshima, Japan

    Kazuaki Chayama

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Correspondence to Hiroshi Aikata.

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Kobayashi, T., Aikata, H., Hatooka, M. et al. Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma. Eur Radiol 25, 3272–3281 (2015). https://doi.org/10.1007/s00330-015-3725-0

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