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BMC Cancer
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Magnetic Resonance Imaging | Research article

Imaging biomarkers for well and moderate hepatocellular carcinoma: preoperative magnetic resonance image and histopathological correlation

Authors: Kun Huang, Zhi Dong, Huasong Cai, Mengqi Huang, Zhenpeng Peng, Ling Xu, Yingmei Jia, Chenyu Song, Zi-Ping Li, Shi-Ting Feng

Published in: BMC Cancer | Issue 1/2019

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Abstract

Background

Our aim of the study is to investigate the feasibility of preoperative prediction for hepatocellular carcinoma (HCC) histological grading using gadoxetic acid-enhanced magnetic resonance imaging (MRI).

Methods

This study included one hundred and fifty-six patients with solitary HCC. Preoperative gadoxetic acid-enhanced MRI findings were retrospectively analyzed. MRI qualitative features such as tumor size, margin, capsule status, signal homogeneity, intratumoral vessels, peritumoral enhancement during mid-arterial phase, peritumoral hypointensity during the hepatobiliary phase (HBP) were investigated. Apparent diffusion coefficients (ADCs), T1 reduction ratio of pre- and post-contrast enhanced images of the tumors were calculated. HCC histological grading in surgical specimens were confirmed by Edmonson’s criteria. Correlations between these MRI features and HCC histological grading were analyzed using multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of the model.

Results

Univariate analysis showed that maximum tumor diameter (p = 0.004), tumor margin (p = 0.006), intratumoral vessels (p = 0.001) and peritumoral hypointensity during HBP (p = 0.000), were significantly correlated with HCC histological grading. There was no relationship between capsule, tumor signal, venous thrombosis, peritumoral enhancement during mid-arterial phase, ADC value, T1 reduction ratio, and HCC histological grading. Multivariate logistic regression analysis demonstrated that the maximum tumor diameter (p = 0.012, odds ratio = 1.002, 95% confidence interval: 1.007–1.046)) was an independent risk factor for high grade HCC.

Conclusions

Greater tumor size, a more irregular margin, presence of intratumoral vessels, and peritumoral hypointensity during HBP were indicators for high grade HCC. The maximum tumor diameter was an independent risk factor for high grade HCC.
Appendix
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Literature
1.
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.CrossRefPubMed
2.
3.
Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Seminars Liver Dis. 2005;25:181–200.CrossRef
4.
Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–7.CrossRefPubMed
5.
Lammer J, Malagari K, Vogl T, et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Inter Rad. 2010;33:41–52.CrossRef
6.
Kamiyama T, Nakanishi K, Yokoo H, et al. Analysis of the risk factors for early death due to disease recurrence or progression within 1 year after hepatectomy in patients with hepatocellular carcinoma. World J Surg Oncol. 2012;10:107.CrossRefPubMedPubMedCentral
7.
Cucchetti A, Piscaglia F, Caturelli E, et al. Comparison of recurrence of hepatocellular carcinoma after resection in patients with cirrhosis to its occurrence in a surveilled cirrhotic population. Ann Surg Oncol. 2009;16:413–22.CrossRefPubMed
8.
Furuse J, Maru Y, Yoshino M, et al. Assessment of arterial tumor vascularity in small hepatocellular carcinoma. Comparison between color doppler ultrasonography and radiographic imagings with contrast medium: dynamic CT, angiography, and CT hepatic arteriography. Eur J Radiol. 2000;36:20–7.CrossRefPubMed
9.
Poon RTP, Ng IOL, Lau C, et al. Tumor microvessel density as a predictor of recurrence after resection of hepatocellular carcinoma: a prospective study. J Clin Oncol. 2002;20:1775–85.CrossRefPubMed
10.
Lai EC, You KT, Ng IO, et al. The pathological basis of resection margin for hepatocellular carcinoma. World J Surg. 1993;17:786–90.CrossRefPubMed
11.
Shi M, Guo RP, Lin XJ, et al. Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial. Ann Surg. 2007;245:36–43.CrossRefPubMedPubMedCentral
12.
Friemel J, Rechsteiner M, Frick L, et al. Intratumor heterogeneity in hepatocellular carcinoma. Clin Cancer Res. 2015;21:1951–61.CrossRefPubMed
13.
Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet. 2002;31:339–46.CrossRefPubMed
14.
Frenette C, Gish RG. Hepatocellular carcinoma: molecular and genomic guideline for the clinician. Clin Liver Dis. 2011;15:307–21.CrossRefPubMed
15.
Stigliano R, Marelli L, Yu D, et al. Seeding following percutaneous diagnostic and therapeutic approaches for hepatocellular carcinoma. What is the risk and the outcome? Seeding risk for percutaneous approach of HCC. Cancer Treat Rev. 2007;33:437–47.CrossRefPubMed
16.
Silva MA, Hegab B, Hyde C, et al. Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis. Gut. 2008;57:1592–6.CrossRefPubMed
17.
Ahn SS, Kim MJ, Lim JS, et al. Added value of gadoxetic acid-enhanced hepatobiliary phase MR imaging in the diagnosis of hepatocellular carcinoma. Radiology. 2010;255:459–66.CrossRefPubMed
18.
Kogita S, Imai Y, Okada M, et al. Gd–EOB-DTPA-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading and portal blood flow. Eur Radiol. 2010;20:2405–13.CrossRefPubMed
19.
Jang HJ, Kim TK, Burns PN, et al. Enhancement patterns of hepatocellular carcinoma at contrast-enhanced US: comparison with histologic differentiation. Radiology. 2007;244:898–906.CrossRefPubMed
20.
Nishie A, Yoshimitsu K, Okamoto D, et al. CT prediction of histological grade of hypervascular hepatocellular carcinoma: utility of the portal phase. Jpn J Radiol. 2013;31:89–98.CrossRefPubMed
21.
Heo SH, Jeong YY, Shin SS, et al. 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. 2010;11:295–303.CrossRefPubMedPubMedCentral
22.
Witjes CD, Willemssen FE, Verheij J, et al. Histological differentiation grade and microvascular invasion of hepatocellular carcinoma predicted by dynamic contrast-enhanced MRI. J Magn Reson Imaging. 2012;36:641–7.CrossRefPubMed
23.
Choi JW, Lee JM, Kim SJ, et al. Hepatocellular carcinoma: imaging patterns on gadoxetic acid-enhanced MR images and their value as an imaging biomarker. Radiology. 2013;267:776–86.CrossRefPubMed
24.
Lee JH, Lee JM, Kim SJ, et al. Enhancement patterns of hepatocellular carcinomas on multiphasic multidetector row CT: comparison with pathological differentiation. Brit J Radiol. 2012;85:E573–83.CrossRefPubMedPubMedCentral
25.
26.
27.
Martins A, Cortez-Pinto H, Marques-Vidal P, et al. Treatment and prognostic factors in patients with hepatocellular carcinoma. Liver Int. 2006;26:680–7.CrossRefPubMed
28.
Chen WT, Chau GY, Lui WY, et al. Recurrent hepatocellular carcinoma after hepatic resection: prognostic factors and long-term outcome. Eur J Surg Oncol. 2004;30:414–20.CrossRefPubMed
29.
Pawlik TM, Delman KA, Vauthey JN, et al. Tumor size predicts vascular invasion and histologic grade: implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl. 2005;11:1086–92.CrossRefPubMed
30.
Liver Cancer Study Group Of Japan. The general rules for the clinical and pathological study of primary liver cancer. Jpn J Surg. 1989;19:98–129.CrossRef
31.
Chou CT, Chen RC, Lin WC, et al. Prediction of microvascular invasion of hepatocellular carcinoma: preoperative CT and histopathologic correlation. Am J Roentgenol. 2014;203(3):W253–9.CrossRef
32.
Ariizumi S, Kitagawa K, Kotera Y, et al. 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. 2011;18:575–85.CrossRefPubMed
33.
Nino-Murcia M, Olcott EW, Jeffrey RB, et al. Focal liver lesions: pattern-based classification scheme for enhancement at arterial phase CT. Radiology. 2000;215:746–51.CrossRefPubMed
34.
Nishie A, Asayama Y, Ishigami K, et al. Clinicopathological significance of the peritumoral decreased uptake area of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid in hepatocellular carcinoma. J Gastroenterol Hepatol. 2014;29:561–7.CrossRefPubMed
35.
Choi BI, Lee KH, Han JK, et al. Hepatic arterioportal shunts: dynamic CT and MR features. Korean J Radiol. 2002;3(1):15.
36.
Tsuda N, Matsui O. Cirrhotic rat liver: reference to transporter activity and morphologic changes in bile canaliculi—gadoxetic acid-enhanced MR imaging. Radiology. 2010;256:767–73.CrossRefPubMed
37.
Tsuboyama T, Onishi H, Kim T, et al. Hepatocellular carcinoma: hepatocyte-selective enhancement at gadoxetic acid-enhanced MR imaging—correlation with expression of sinusoidal and canalicular transporters and bile accumulation. Radiology. 2010;255:824–33.CrossRefPubMed
38.
Nakashima Y, Nakashima O, Tanaka M, et al. Portal vein invasion and intrahepatic micrometastasis in small hepatocellular carcinoma by gross type. Hepatol Res. 2003;26:142–7.CrossRefPubMed
39.
Kanai T, Hirohashi S, Upton MP, et al. Pathology of small hepatocellular carcinoma. A proposal for a new gross classification. Cancer. 1987;60:810–9.CrossRefPubMed
40.
Hui AM, Takayama T, Sano K, et al. Predictive value of gross classification of hepatocellular carcinoma on recurrence and survival after hepatectomy. J Hepatol. 2000;33:975–9.CrossRefPubMed
41.
Freeny PC. Portal vein tumor thrombus: demonstration by computed tomographic ateriography. J Comput Assist Tomogr. 1980;4:263–4.CrossRefPubMed
42.
Pomfret EA, Washburn K, Wald C, et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl. 2010;16:262–78.CrossRefPubMed
43.
Suh YJ, Kim MJ, Choi JY, et al. Preoperative prediction of the microvascular invasion of hepatocellular carcinoma with diffusion-weighted imaging. Liver Transpl. 2012;18:1171–8.CrossRefPubMed
44.
Grazioli L, Olivetti L, Fugazzola C, et al. The pseudocapsule in hepatocellular carcinoma: correlation between dynamic MR imaging and pathology. Eur Radiol. 1999;9:62–7.CrossRefPubMed
45.
Lim JH, Choi D, Park CK, et al. Encapsulated hepatocellular carcinoma: CT-pathologic correlations. Eur Radiol. 2006;16:2326–33.CrossRefPubMed
46.
Khatri G, Merrick L, Miller FH. MR imaging of hepatocellular carcinoma. Magn Reson Imaging Clin N Am. 2010;18:421–50.CrossRefPubMed
47.
Choi JY, Lee JM, Sirlin CB. CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. development, growth, and spread: key pathologic and imaging aspects. Radiology. 2014;272:635–54.CrossRefPubMed
48.
49.
Ishigami K, Yoshimitsu K, Nishihara Y, et al. Hepatocellular carcinoma with a pseudocapsule on gadolinium-enhanced MR images: correlation with histopathologic findings. Radiology. 2009;250:435–43.CrossRefPubMed
50.
Iguchi T, Aishima S, Sanefuji K, et al. 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 Oncol. 2009;16:2539–46.CrossRefPubMed
51.
Tsai TJ, Chau GY, Lui WY, et al. Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma. Surgery. 2000;127:603–8.CrossRefPubMed
52.
Colecchia A, Scaioli E, Montrone L, et al. Pre-operative liver biopsy in cirrhotic patients with early hepatocellular carcinoma represents a safe and accurate diagnostic tool for tumour grading assessment. J Hepatol. 2011;54:300–5.CrossRefPubMed
53.
Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiav M, Mariani L, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35–43.CrossRefPubMed
54.
Nakanishi M, Chuma M, Hige S, et al. Relationship between diffusion-weighted magnetic resonance imaging and histological tumor grading of hepatocellular carcinoma. Ann Surg Oncol. 2012;19:1302–9.CrossRefPubMed
55.
Galea N, Cantisani V, Taouli B. Liver lesion detection and characterization: role of diffusion-weighted imaging. J Magn Reson Imaging. 2013;37:1260–76.CrossRefPubMed
56.
Peng Z, Jiang M, Cai H, et al. Gd-EOB-DTPA-enhanced magnetic resonance imaging combined with T1 mapping predicts the degree of differentiation in hepatocellular carcinoma. BMC Cancer. 2016;16:625.CrossRefPubMedPubMedCentral
57.
Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. The Lancet Oncology. 2009;10:35–43.CrossRefPubMed
58.
Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.CrossRefPubMed
Metadata
Title
Imaging biomarkers for well and moderate hepatocellular carcinoma: preoperative magnetic resonance image and histopathological correlation
Authors
Kun Huang
Zhi Dong
Huasong Cai
Mengqi Huang
Zhenpeng Peng
Ling Xu
Yingmei Jia
Chenyu Song
Zi-Ping Li
Shi-Ting Feng
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5574-8

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