Elsevier

Journal of Hepatology

Volume 67, Issue 3, September 2017, Pages 526-534
Journal of Hepatology

Research Article
Preoperative gadoxetic acid–enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma

https://doi.org/10.1016/j.jhep.2017.04.024Get rights and content

Highlights

  • MR imaging features were independent predictors for microvascular invasion of HCC.

  • MR imaging findings can be used as a biomarker for microvascular invasion of HCC.

  • A combination of MR imaging findings is associated with early recurrence of HCC.

Background & Aims

This study aimed to identify preoperative magnetic resonance (MR) imaging biomarkers for predicting microvascular invasion (MVI), to determine their diagnostic performance and to evaluate whether they are associated with early recurrence after surgery for single hepatocellular carcinoma (HCC).

Methods

The study included 197 patients with surgically resected HCC (≤5 cm) who underwent preoperative gadoxetic acid–enhanced MR imaging. Significant MR imaging findings for predicting MVI were identified by univariate and multivariate analyses. Early recurrence rates (<2 years) were analyzed with respect to significant imaging findings for predicting MVI.

Results

Three MR imaging features were independently associated with MVI: arterial peritumoral enhancement (odds ratio [OR] = 5.184; 95% confidence interval [CI]: 2.228, 12.063; p <0.001), non-smooth tumor margin (OR = 3.555; 95% CI: 1.627, 7.769; p = 0.001), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR = 4.705; 95% CI: 1.671, 13.246; p = 0.003). When two of three findings were combined, the specificity was 92.5% (124/134). When all three findings were satisfied, the specificity was 99.3% (133/134). Early recurrence rates were significantly higher in patients with single HCC, with two or three significant MR imaging findings, compared to those with none (27.9% vs. 12.6%, respectively, p = 0.030).

Conclusions

A combination of two or more of the following; arterial peritumoral enhancement, non-smooth tumor margin, and peritumoral hypointensity on HBP, can be used as a preoperative imaging biomarker for predicting MVI, with specificity >90%, and is associated with early recurrence after surgery of single HCC.

Lay summary: A combination of two or more of the following; arterial peritumoral enhancement, non-smooth tumor margin, and peritumoral hypointensity on hepatobiliary phase, can be used as a preoperative imaging biomarker for predicting microvascular invasion, with specificity >90%, and is associated with early recurrence after curative resection of single HCC.

Introduction

Vascular invasion, either macrovascular or microvascular invasion (MVI), is a well-known major prognostic factor of hepatocellular carcinoma (HCC), after surgical resection or liver transplantation.[1], [2], [3], [4] In particular, MVI of HCC is a major risk factor for early recurrence during the first 2 years after curative treatment.[5], [6] Although macrovascular invasion can be frequently detected prior to surgery by complementary imaging modalities, including computed tomography (CT) and magnetic resonance (MR) imaging, MVI can rarely be determined preoperatively because it is a histopathological diagnosis. It is therefore of great importance to identify preoperative imaging biomarkers for predicting MVI.

Several studies have reported that certain imaging findings including tumor size,[7], [8] arterial rim enhancement9 or peritumoral enhancement,[7], [8], [9] tumor margin,[8], [10] tumor hypointensity11 or peritumoral hypointensity on hepatobiliary phase (HBP),12 radiological capsule10 on gadoxetic acid–enhanced MR imaging, and higher tumor-to-liver signal intensity (SI) ratio and lower apparent diffusion coefficient (ADC) value on diffusion-weighted (DW) imaging with ADC map,[13], [14], [15] are useful for predicting MVI of HCC. Although these studies have reported imaging features for predicting MVI, there is still debate over which best reflects the MVI of HCC, which results in early recurrence after hepatic resection. Kim et al.16 and Ahn et al.7 suggested that arterial peritumoral enhancement was associated with a high probability of MVI. Ariizumi et al.10 revealed that only non-smooth margin was an independent predictor of MVI, whereas Kim et al.12 reported that only peritumoral hypointensity on HBP was significant in predicting MVI. Also, in previous studies using resected tumor, HCC larger than 5 cm in maximum diameter showed a greater chance of spreading through MVI.[17], [18], [19] An et al.9 demonstrated that MR imaging findings such as arterial rim, peritumoral enhancement and tumor size were independently associated with early recurrence. However, to the best of our knowledge, there have been few attempts to evaluate the diagnostic performance of the most significant MR imaging features and their combinations for predicting MVI of HCC and the risk of early recurrence. In addition, there are limited studies that have investigated MR imaging findings for predicting MVI for HCC with diameter of 5 cm or smaller.

The purpose of this study was to identify preoperative MR imaging biomarkers for predicting MVI, to determine their diagnostic performance and to evaluate whether they are associated with early recurrence after curative resection of single HCC ≤5 cm.

Section snippets

Materials and methods

The institutional review board approved this retrospective study and waived the requirement for informed consent.

Results

Among 197 HCCs, 63 had MVI, while 134 had no MVI. Comparisons of clinicopathologic characteristics between HCCs with or without MVI are summarized in Table 1. Baseline variables, including age, sex, background liver, and origin of liver disease, were similar in both groups (p >0.05). For serum levels of tumor markers, HCCs with MVI showed more abnormal and higher serum AFP and PIVKA-II levels than those without MVI (p = 0.004 and p = 0.004, respectively; normal reference values of AFP and PIVKA-II

Discussion

Our results demonstrated that arterial peritumoral enhancement, non-smooth tumor margin, and peritumoral hypointensity on gadoxetic acid–enhanced HBP images were independent and significant predictors of MVI of HCCs, with good or excellent interobserver agreement. Combining two or three MR imaging findings for predicting MVI resulted in specificity greater than 92%. In addition, early recurrence rate was significantly higher in patients with two or three MR imaging findings compared to those

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Authors’ contributions

  • Dr Seong Hyun Kim had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Dr Sunyoung Lee contributed to the study concept and design, acquisition of data, statistical analysis, analysis and interpretation of data, and drafting of the manuscript.

  • Dr Seong Hyun Kim contributed to the study concept and design, analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript

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