European Radiology

, Volume 29, Issue 2, pp 1003–1012 | Cite as

Pre-operative ADC predicts early recurrence of HCC after curative resection

  • Sunyoung Lee
  • Seong Hyun KimEmail author
  • Jeong Ah Hwang
  • Ji Eun Lee
  • Sang Yun Ha



To assess a correlation between the preoperative diffusion-weighted imaging (DWI) and early recurrence (<2 years) and to determine the best DWI parameters as the risk factor of early recurrence after surgery in single hepatocellular carcinoma (HCC).


The study included 114 patients with surgically resected single HCC (≤5 cm) who underwent preoperative magnetic resonance imaging (MRI) with DWI. Radiologists evaluated the diffusion restriction of the tumours using qualitative assessment and the mean and minimum apparent diffusion coefficient values (ADCmean and ADCmin) of the tumours using quantitative measurement. Clinical and laboratory findings and DWI parameters as a risk factor for early recurrence were identified by using Cox proportional hazards model.


No significant difference was observed in early recurrence rates of HCCs between those with and those without diffusion restriction (p = 0.484). Early recurrence rates of HCCs with ADCmean and ADCmin values lower than the optimal cut-offs (1.023 and 0.773 × 10-3 mm2/s, respectively) were significantly higher compared with those with values higher than the optimal cut-offs (p = 0.001 and p < 0.001, respectively). In the multivariable analysis, tumour size [hazard ratio (HR) per centimetre, 2.011; 95% CI, 1.304-3.102; p = 0.002] and ADCmin ≤0.773 × 10-3 mm2/s (HR, 13.339; 95% CI, 4.422-40.240; p < 0.001) were independent risk factors for early HCC recurrence.


DWI is a promising imaging tool for early recurrence of HCC. Among qualitative and quantitative assessments of DWI, ADCmin is a significant risk factor for early recurrence after surgery in single HCC.

Key Points

• The performance of minimum apparent diffusion coefficient (ADCmin) is significantly better than that of mean apparent diffusion coefficient (ADCmean) for identifying early recurrence.

• ADCmin is a significantly independent risk factor of early HCC recurrence after surgery.

• ADCmin correlates with early recurrence after curative resection of single HCC, reflecting histopathological features of the tumours including histological grade and microvascular invasion.


Hepatocellular carcinoma Magnetic resonance imaging Diffusion-weighted imaging Early recurrence 





Hepatobiliary phase


Hepatocellular carcinoma


Hazard ratio


Microvascular invasion


Protein induced by vitamin K absence or antagonist-II



The authors state that this work has not received any funding.

Compliance with ethical standards


The scientific guarantor of this publication is Seong Hyun Kim.

Conflict of interest

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.

Statistics and biometry

One of the authors has significant statistical expertise.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.


• retrospective

• prognostic study

• performed at one institution


  1. 1.
    Taouli B, Vilgrain V, Dumont E, Daire JL, Fan B, Menu Y (2003) Evaluation of liver diffusion isotropy and characterization of focal hepatic lesions with two single-shot echo-planar MR imaging sequences: prospective study in 66 patients. Radiology 226:71–78CrossRefGoogle Scholar
  2. 2.
    Parikh T, Drew SJ, Lee VS et al (2008) Focal liver lesion detection and characterization with diffusion-weighted MR imaging: comparison with standard breath-hold T2-weighted imaging. Radiology 246:812–822CrossRefGoogle Scholar
  3. 3.
    Taouli B, Koh DM (2010) Diffusion-weighted MR imaging of the liver. Radiology 254:47–66CrossRefGoogle Scholar
  4. 4.
    Mitchell DG, Bruix J, Sherman M, Sirlin CB (2015) LI-RADS (Liver Imaging Reporting and Data System): summary, discussion, and consensus of the LI-RADS Management Working Group and future directions. Hepatology 61:1056–1065CrossRefGoogle Scholar
  5. 5.
    Cha DI, Jang KM, Kim SH, Kang TW, Song KD (2017) Liver Imaging Reporting and Data System on CT and gadoxetic acid-enhanced MRI with diffusion-weighted imaging. Eur Radiol 27:4394–4405CrossRefGoogle Scholar
  6. 6.
    Muhi A, Ichikawa T, Motosugi U et al (2009) High-b-value diffusion-weighted MR imaging of hepatocellular lesions: estimation of grade of malignancy of hepatocellular carcinoma. J Magn Reson Imaging 30:1005–1011CrossRefGoogle Scholar
  7. 7.
    Heo SH, Jeong YY, Shin SS et al (2010) Apparent diffusion coefficient value of diffusion-weighted imaging for hepatocellular carcinoma: correlation with the histologic differentiation and the expression of vascular endothelial growth factor. Korean J Radiol 11:295–303CrossRefGoogle Scholar
  8. 8.
    Nishie A, Tajima T, Asayama Y et al (2011) Diagnostic performance of apparent diffusion coefficient for predicting histological grade of hepatocellular carcinoma. Eur J Radiol 80:e29–e33CrossRefGoogle Scholar
  9. 9.
    An C, Park MS, Jeon HM et al (2012) Prediction of the histopathological grade of hepatocellular carcinoma using qualitative diffusion-weighted, dynamic. and hepatobiliary phase MRI. Eur Radiol 22:1701–1708Google Scholar
  10. 10.
    Nakanishi M, Chuma M, Hige S et al (2012) Relationship between diffusion-weighted magnetic resonance imaging and histological tumor grading of hepatocellular carcinoma. Ann Surg Oncol 19:1302–1309CrossRefGoogle Scholar
  11. 11.
    Okamura S, Sumie S, Tonan T et al (2016) Diffusion-weighted magnetic resonance imaging predicts malignant potential in small hepatocellular carcinoma. Dig Liver Dis 48:945–952CrossRefGoogle Scholar
  12. 12.
    Suh YJ, Kim MJ, Choi JY, Park MS, Kim KW (2012) Preoperative prediction of the microvascular invasion of hepatocellular carcinoma with diffusion-weighted imaging. Liver Transpl 18:1171–1178CrossRefGoogle Scholar
  13. 13.
    Zhao J, Li X, Zhang K et al (2017) Prediction of microvascular invasion of hepatocellular carcinoma with preoperative diffusion-weighted imaging: A comparison of mean and minimum apparent diffusion coefficient values. Medicine (Baltimore) 96:e7754CrossRefGoogle Scholar
  14. 14.
    European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol.
  15. 15.
    Heimbach JK, Kulik LM, Finn RS et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67:358–380CrossRefGoogle Scholar
  16. 16.
    Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J (2000) Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer 89:500–507CrossRefGoogle Scholar
  17. 17.
    Imamura H, Matsuyama Y, Tanaka E et al (2003) Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 38:200–207CrossRefGoogle Scholar
  18. 18.
    Portolani N, Coniglio A, Ghidoni S et al (2006) Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg 243:229–235CrossRefGoogle Scholar
  19. 19.
    Cucchetti A, Piscaglia F, Caturelli E et al (2009) Comparison of recurrence of hepatocellular carcinoma after resection in patients with cirrhosis to its occurrence in a surveilled cirrhotic population. Ann Surg Oncol 16:413–422CrossRefGoogle Scholar
  20. 20.
    Padhani AR, Liu G, Koh DM et al (2009) Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations. Neoplasia 11:102–125CrossRefGoogle Scholar
  21. 21.
    Choi JY, Lee JM, Sirlin CB (2014) CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part II. Extracellular agents, hepatobiliary agents, and ancillary imaging features. Radiology 273:30–50CrossRefGoogle Scholar
  22. 22.
    Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 7:462–503CrossRefGoogle Scholar
  23. 23.
    Thoeny HC, De Keyzer F, Vandecaveye V et al (2005) Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging. Radiology 237:492–499CrossRefGoogle Scholar
  24. 24.
    Deng J, Rhee TK, Sato KT et al (2006) In vivo diffusion-weighted imaging of liver tumor necrosis in the VX2 rabbit model at 1. 5 Tesla. Invest Radiol 41:410–414CrossRefGoogle Scholar
  25. 25.
    Chen CY, Li CW, Kuo YT et al (2006) Early response of hepatocellular carcinoma to transcatheter arterial chemoembolization: choline levels and MR diffusion constants—initial experience. Radiology 239:448–456CrossRefGoogle Scholar
  26. 26.
    Nasu K, Kuroki Y, Tsukamoto T, Nakajima H, Mori K, Minami M (2009) Diffusion-weighted imaging of surgically resected hepatocellular carcinoma: imaging characteristics and relationship among signal intensity, apparent diffusion coefficient. and histopathologic grade. AJR Am J Roentgenol 193:438–444CrossRefGoogle Scholar
  27. 27.
    Nakashima O, Kojiro M (2001) Recurrence of hepatocellular carcinoma: multicentric occurrence or intrahepatic metastasis? A viewpoint in terms of pathology. J Hepatobiliary Pancreat Surg 8:404–409CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Sunyoung Lee
    • 1
    • 2
  • Seong Hyun Kim
    • 1
    Email author
  • Jeong Ah Hwang
    • 1
    • 3
  • Ji Eun Lee
    • 1
    • 4
  • Sang Yun Ha
    • 5
  1. 1.Department of Radiology and Center for Imaging Science, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
  2. 2.Department of Radiology and Research Institute of Radiological Science, Severance HospitalYonsei University College of MedicineSeoulKorea
  3. 3.Department of Radiology, Soonchunhyang University College of MedicineCheonan HospitalCheonan-siKorea
  4. 4.Department of Radiology, Soonchunhyang University College of MedicineBucheon HospitalBucheon-siKorea
  5. 5.Department of Pathology, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea

Personalised recommendations