The prediction of microvascular invasion of hepatocellular carcinoma using multiple imaging modalities

Abstract

To implement an adequate treatment strategy for solitary hepatocellular carcinoma (HCC), the prediction of microvascular invasion (MVI) is crucial. Metastatic recurrences after curative treatments can result from occult metastasis derived from invisible MVI. For predicting MVI, poorly differentiated or non-singular nodular HCC with a high risk of MVI should be evaluated by common imaging modalities such as ultrasound, contrast enhanced computed tomography (CECT), or magnetic resonance imaging (MRI). Summarizing these predictabilities in previous reports, the accuracies for predicting MVI were 78% in contrast enhanced ultrasonography (CEUS), 76%-89% in CECT, and 62%-77% in MRI. Those for predicting poor differentiation were 69%-92% in CEUS, 52%-90% in CECT, and 71%-75% in MRI. Those for predicting non-singular nodular type were 92%-95% in CEUS, 81%-89% in MRI, and 91%-93% in the combination of MRI and CECT. Among common imaging modalities, MRI can provide tissue characterization of the HCC using signal intensity. Gadolinium-ethoxybenzyl diethylenetriamine penta-acetic acid-enhanced MRI including diffusion imaging is the most informative imaging modality to predict MVI. Combination of MRI with other imaging modalities or tumor markers may provide a more accurate predicting for MVI. HCC with a high risk of MVI should be treated as advanced HCC even after curative treatment.

Keywords

Hepatocellular carcinoma / microvascular invasion / histologic differentiation / ultrasound / computed tomography / magnetic resonance imaging

References

[1] Yuki K,Sakamoto M,Shimosato Y.Growth and spread of hepatocellular carcinoma. A review of 240 consecutive autopsy cases..Cancer1990;66:2174-9

[2] Kudo M.Multistep human hepatocarcinogenesis: correlation of imaging with pathology..J Gastroenterol.2009;44 Suppl 19:112-8

[3] Fukuda S,Nakahara H,Ohdan H.Clinicopathologic features and prognostic factors of resected solitary small-sized hepatocellular carcinoma..Hepatogastroenterology2005;52:1163-7

[4] Esnaola NF,Mirza NQ,Doherty D.Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation..J Gastrointest Surg2002;6:224-32

[5] Iguchi T,Sanefuji K,Sugimachi K.Both fibrous capsule formation and extracapsular penetration are powerful predictors of poor survival in human hepatocellular carcinoma: a histological assessment of 365 patients in Japan..Ann Surg Oncol2009;16:2539-46

[6] Kanai T,Upton MP,Kishi K.Pathology of small hepatocellular carcinoma. A proposal for a new gross classification..Cancer1987;60:810-9

[7] Hui AM,Sano K,Akahane M.Predictive value of gross classification of hepatocellular carcinoma on recurrence and survival after hepatectomy..J Hepatol2000;33:975-9

[8] Shimada M,Hamatsu T,Terashi T.The role of macroscopic classification in nodular-type hepatocellular carcinoma..Am J Surg2001;182:177-82

[9] Nakashima Y,Tanaka M,Nakashima M.Portal vein invasion and intrahepatic micrometastasis in small hepatocellular carcinoma by gross type..Hepatol Res2003;26:142-7

[10] Moribata K,Shingaki N,Enomoto S.Assessment of malignant potential of small hypervascular hepatocellular carcinoma using B-mode ultrasonography..Hepatol Res2011;41:233-9

[11] Sugimoto K,Kamiyama N,Yamada M.Analysis of morphological vascular changes of hepatocellular carcinoma by microflow imaging using contrast-enhanced sonography..Hepatol Res2008;38:790-9

[12] Tanaka H,Higashiura A,Ishii A.New malignant grading system for hepatocellular carcinoma using the Sonazoid contrast agent for ultrasonography..J Gastroenterol2014;49:755-63

[13] Xia Y,Dai Q,Lv K.Contrast-enhanced ultrasound of hepatocellular carcinoma: correlation of washout time and angiogenesis..Clin Hemorheol Microcirc2011;48:265-73

[14] Xu JF,Shi Y,Wu Y.Evaluation of hepatocellular carcinoma by contrast-enhanced sonography: correlation with pathologic differentiation..J Ultrasound Med2011;30:625-33

[15] Pei XQ,Liu M,Han F.Contrast-enhanced ultrasonography of hepatocellular carcinoma: correlation between quantitative parameters and histological grading..Br J Radiol2012;85:e740-7 PMCID:PMC3487094

[16] Loria F,Basile S,Randazzo D.Contrast-enhanced ultrasound of hepatocellular carcinoma: correlation between enhancement pattern and cellular differentiation on histopathlogy..Updates Surg2012;64:247-55

[17] Feng Y,Luo Y,Zhou X.Efficacy of contrast-enhanced ultrasound washout rate in predicting hepatocellular carcinoma differentiation..Ultrasound Med Biol2015;41:1553-60

[18] Hatanaka K,Kudo M,Minami Y.Usefulness of the post-vascular phase of contrast-enhanced ultrasonography with sonazoid in the evaluation of gross types of hepatocellular carcinoma..Oncology.2010;78 Suppl 1:53-9

[19] Tada T,Toyoda H,Sone Y.Utility of contrast-enhanced ultrasound with perflubutane for diagnosing the macroscopic type of small nodular hepatocellular carcinomas..Eur Radiol2014;24:2157-66

[20] Hatanaka K,Kudo M,Chung H.The gross classification of hepatocellular carcinoma: usefulness of contrast-enhanced US..J Clin Ultrasound2014;42:1-8

[21] Nuta J,Ida Y,Hayami S.Irregular defects in hepatocellular carcinomas during the Kupffer phase of contrast-enhanced ultrasonography with perfluorobutane microbubbles: pathological features and metastatic recurrence after surgical resection..Ultrasound Med Biol2017;43:1829-36

[22] Asayama Y,Nishihara Y,Aishima S.Arterial blood supply of hepatocellular carcinoma and histologic grading: radiologic-pathologic correlation..AJR Am J Roentgenol2008;190:W28-34

[23] Sanada Y,Itoh H.Comparison of CT enhancement patterns and histologic features in hepatocellular carcinoma up to 2 cm: assessment of malignant potential with claudin-10 immunohistochemistry..Oncol Rep2007;17:1177-82

[24] Kawamura Y,Hirakawa M,Sezaki H.New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma..Hepatol Res2010;40:1006-14

[25] Nishie A,Okamoto D,Asayama Y.CT prediction of histological grade of hypervascular hepatocellular carcinoma: utility of the portal phase..Jpn J Radiol2013;31:89-98

[26] Nakachi K,Mori Y,Moribata K.Prediction of poorly differentiated hepatocellular carcinoma using contrast computed tomography..Cancer Imaging2014;14:7 PMCID:PMC4331839

[27] Lee JH,Kim SJ,Yun SH.Enhancement patterns of hepatocellular carcinomas on multiphasicmultidetector row CT: comparison with pathological differentiation..Br J Radiol2012;85:e573-83 PMCID:PMC3487070

[28] Chou CT,Lee CW,Wu HK.Prediction of microvascular invasion of hepatocellular carcinoma by pre-operative CT imaging..Br J Radiol2012;85:778-83 PMCID:PMC3474124

[29] Chou CT,Lin WC,Chen CB.Prediction of microvascular invasion of hepatocellular carcinoma: preoperative CT and histopathologic correlation..AJR Am J Roentgenol2014;203:W253-9

[30] Reginelli A,Sgrazzutti C,Serra N.Vascular microinvasion from hepatocellular carcinoma: CT findings and pathologic correlation for the best therapeutic strategies..Med Oncol2017;34:93

[31] Wu TH,Yamanaka K,Taura K.A non-smooth tumor margin on preoperative imaging predicts microvascular invasion of hepatocellular carcinoma..Surg Today2016;46:1275-81

[32] Hu H,Huang Y,Lai ZC.A non-smooth tumor margin on preoperative imaging assesses microvascular invasion of hepatocellular carcinoma: a systematic review and meta-analysis..Sci Rep2017;7:15375 PMCID:PMC5684346

[33] Banerjee S,Kim HJ,Chan MG.A computed tomography radiogenomic biomarker predicts microvascular invasion and clinical outcomes in hepatocellular carcinoma..Hepatology2015;62:792-800 PMCID:PMC4654334

[34] Zhao H,Dai T,Tang M.Development and validation of a novel predictive scoring model for microvascular invasion in patients with hepatocellular carcinoma..Eur J Radiol2017;88:32-40

[35] Muramatsu Y,Takayasu K,Yamada T.Early hepatocellular carcinoma: MR imaging..Radiology1991;181:209-13

[36] Kadoya M,Takashima T.Hepatocellular carcinoma: correlation of MR imaging and histopathologic findings..Radiology1992;183:819-25

[37] Ebara M,Kojima Y,Yoshikawa M.Small hepatocellular carcinoma: relationship of signal intensity to histopathologic findings and metal content of the tumor and surrounding hepatic parenchyma..Radiology1999;210:81-8

[38] Enomoto S,Shingaki N,Moribata K.Assessment of hepatocellular carcinomas using conventional magnetic resonance imaging correlated with histological differentiation and a serum marker of poor prognosis..Hepatol Int2011;5:730-7 PMCID:PMC3090556

[39] Min JH,Lim S,Choi D.Prediction of microvascular invasion of hepatocellular carcinomas with gadoxetic acid-enhanced MR imaging: impact of intra-tumoral fat detected on chemical-shift images..Eur J Radiol2015;84:1036-43

[40] Heo SH,Shin SS,Lim HS.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 Radiol2010;11:295-303 PMCID:PMC2864856

[41] Nishie A,Asayama Y,Kakihara D.Diagnostic performance of apparent diffusion coefficient for predicting histological grade of hepatocellular carcinoma..Eur J Radiol2011;80:e29-33

[42] Nakanishi M,Hige S,Yokoo H.Relationship between diffusion-weighted magnetic resonance imaging and histological tumor grading of hepatocellular carcinoma..Ann Surg Oncol2012;19:1302-9

[43] Tang Y,Ma L,Yu G.Diffusion-weighted imaging of hepatocellular carcinomas: a retrospective analysis of correlation between apparent diffusion coefficients and histological grade..Abdom Radiol (NY)2016;41:1539-45

[44] Li X,Shi Y,Meng X.Correlations between the minimum and mean apparent diffusion coefficient values of hepatocellular carcinoma and tumor grade..J Magn Reson Imaging2016;44:1442-7

[45] Xu P,Liu K,Xu C.Microvascular invasion in small hepatocellular carcinoma: is it predictable with preoperative diffusion-weighted imaging?.J Gastroenterol Hepatol2014;29:330-6

[46] Suh YJ,Choi JY,Kim KW.Preoperative prediction of the microvascular invasion of hepatocellular carcinoma with diffusion-weighted imaging..Liver Transpl2012;18:1171-8

[47] Okamura S,Tonan T,Satani M.Diffusion-weighted magnetic resonance imaging predicts malignant potential in small hepatocellular carcinoma..Dig Liver Dis2016;48:945-52

[48] Chen J,Liu R,Gao R.Preoperative evaluation of the histological grade of hepatocellular carcinoma with diffusion-weighted imaging: a meta-analysis..PLoS One2015;10:e0117661 PMCID:PMC4320049

[49] Park IK,Cho ES,Chung JJ.Apparent diffusion coefficient of hepatocellular carcinoma on diffusion-weighted imaging: histopathologic tumor grade versus arterial vascularity during dynamic magnetic resonance imaging..PLoS One2018;13:e0197070 PMCID:PMC5947906

[50] Moriya T,Tajima Y,Araki Y.3D analysis of apparent diffusion coefficient histograms in hepatocellular carcinoma: correlation with histological grade..Cancer Imaging2017;17:1 PMCID:PMC5217316

[51] Ogihara Y,Iwasa Y,Himeno Y.Prediction of histological grade of hepatocellular carcinoma using quantitative diffusion-weighted MRI: a retrospective multivendor study..Br J Radiol2018;91:20170728 PMCID:PMC5965986

[52] Iwasa Y,Tateishi U,Ban D.Hepatocellular carcinoma histological grade prediction: a quantitative comparison of diffusion-weighted, T2-weighted, and hepatobiliary-phase magnetic resonance imaging..J Comput Assist Tomogr2016;40:463-70

[53] Mori Y,Shingaki N,Deguchi H.Signal intensity of small hepatocellular carcinoma on apparent diffusion coefficient mapping and outcome after radiofrequency ablation..Hepatol Res2015;45:75-87

[54] Zhao W,Liu H,Hou J.Preoperative prediction of microvascular invasion of hepatocellular carcinoma with IVIM diffusion-weighted MR imaging and Gd-EOB-DTPA-enhanced MR imaging..PLoS One2018;13:e0197488 PMCID:PMC5957402

[55] Wang WT,Yang ZX,Ding Y.Assessment of microvascular invasion of hepatocellular carcinoma with diffusion kurtosis imaging..Radiology2018;286:571-80

[56] Chang WC,Chou CT,Yu CY.Histological grade of hepatocellular carcinoma correlates with arterial enhancement on gadoxetic acid-enhanced and diffusion-weighted MR images..Abdom Imaging2014;39:1202-12

[57] Kim KA,Jeon HM,Choi JS.Prediction of microvascular invasion of hepatocellular carcinoma: usefulness of peritumoral hypointensity seen on gadoxetate disodium-enhanced hepatobiliary phase images..J Magn Reson Imaging2012;35:629-34

[58] Lee S,Lee JE,Park CK.Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma..J Hepatol2017;67:526-34

[59] Hu HT,Wang Z,Huang XW.Peritumoral tissue on preoperative imaging reveals microvascular invasion in hepatocellular carcinoma: a systematic review and meta-analysis..Abdom Radiol (NY)2018;43:3324-30

[60] Tada T,Toyoda H,Sone Y.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 Gastroenterol2015;50:85-94

[61] Chen C,Fu X,Tang M.Contrast-enhanced computed tomography plus gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging for gross classification of hepatocellular carcinoma..Oncotarget2017;8:29741-50 PMCID:PMC5444699

[62] Kobayashi T,Hatooka M,Morio R.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 Radiol2015;25:3272-81

[63] Iwamoto T,Kogita S,Sawai Y.Comparison of contrast-enhanced ultrasound and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI for the diagnosis of macroscopic type of hepatocellular carcinoma..Dig Dis2016;34:679-86

[64] Sasaki M,Watanabe Y,Ida M.Variability in absolute apparent diffusion coefficient values across different platforms may be substantial: a multivendor, multi-institutional comparison study..Radiology2008;249:624-30

[65] Hirokawa F,Miyamoto Y,Shimizu T.Outcomes and predictors of microvascular invasion of solitary hepatocellular carcinoma..Hepatol Res2014;44:846-53

[66] Masuda T,Okabe H,Imai K.Predictive factors of pathological vascular invasion in hepatocellular carcinoma within 3 cm and three nodules without radiological vascular invasion..Hepatol Res2016;46:985-91

[67] Kobayashi T,Honda F,Nakamura Y.Preoperative fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography for prediction of microvascular invasion in small hepatocellular carcinoma..J Comput Assist Tomogr2016;40:524-30

[68] Zhang X,Shen F.Significance of presence of microvascular invasion in specimens obtained after surgical treatment of hepatocellular carcinoma..J Gastroenterol Hepatol2018;33:347-54

[69] Shirabe K,Kimura K,Ikeda T.New scoring system for prediction of microvascular invasion in patients with hepatocellular carcinoma..Liver Int2014;34:937-41