Case Control Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2019; 25(21): 2636-2649
Published online Jun 7, 2019. doi: 10.3748/wjg.v25.i21.2636
Gadoxetic acid-enhanced magnetic resonance imaging can predict the pathologic stage of solitary hepatocellular carcinoma
Yi-Chen Chou, I-Ha Lao, Pei-Ling Hsieh, Ying-Ying Su, Chee-Wai Mak, Ding-Ping Sun, Ming-Jen Sheu, Hsing-Tao Kuo, Tzu-Ju Chen, Chung-Han Ho, Yu-Ting Kuo
Yi-Chen Chou, I-Ha Lao, Pei-Ling Hsieh, Ying-Ying Su, Chee-Wai Mak, Department of Medical Imaging, Chi Mei Medical Center, Tainan 710, Taiwan
I-Ha Lao, Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan
I-Ha Lao, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Ding-Ping Sun, Department of Surgery, Chi Mei Medical Center, Tainan 710, Taiwan
Ding-Ping Sun, Department of Food Science and Technology, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan
Ming-Jen Sheu, Hsing-Tao Kuo, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 710, Taiwan
Ming-Jen Sheu, Department of Medicinal Chemistry, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan
Hsing-Tao Kuo, Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan
Tzu-Ju Chen, Department of Pathology, Chi-Mei Medical Center, Tainan 710, Taiwan
Tzu-Ju Chen, Department of Optometry, Chung Hwa University of Medical Technology, Tainan 717, Taiwan
Tzu-Ju Chen, Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan
Chung-Han Ho, Department of Medical Research, Chi-Mei Medical Center, Tainan 710, Taiwan
Chung-Han Ho, Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan
Yu-Ting Kuo, Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Yu-Ting Kuo, Department of Radiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Author contributions: All authors participated in the research. Kuo YT obtained funding, designed methodology, supervised the research, and wrote the article. Chou YC conducted investigations and wrote the original draft. Lao IH, Hsieh PL, Su YY, May CW, Sun DP, Sheu MJ, Kuo HT, and Chen TJ contributed to clinical survey and input of research methodology. Ho CH performed data curation and statistical analysis.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Chi Mei Medical Center, Taiwan. IRB Serial No. 10702-007.
Informed consent statement: The need for informed consent was waived by the Institutional Review Board of Chi Mei Medical Center, Taiwan because of the retrospective nature of the study.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
Data sharing statement: No additional data are available.
STROBE statement: The manuscript was prepared according to the STROBE checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yu-Ting Kuo, MD, PhD, Doctor, Department of Medical Imaging, Chi Mei Medical Center, 901 Chung-Hwa Road, Yung-Kang District, Tainan 710, Taiwan. y.kuo@mail.chimei.org.tw
Telephone: +886-6-2812811
Received: February 22, 2019
Peer-review started: February 22, 2019
First decision: March 27, 2019
Revised: April 30, 2019
Accepted: May 8, 2019
Article in press: May 8, 2019
Published online: June 7, 2019
Processing time: 104 Days and 9.5 Hours
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Higher pathologic stage of HCC has higher risk of recurrence and shorter survival. However, accurate prediction of pathologic stage from current pre-treatment imaging features is still difficult.

Research motivation

Modern magnetic resonance imaging (MRI) techniques using tissue-specific contrast agents provide many imaging features. We hypothesize that these imaging features may help to determine or predict pathologic stage of HCC.

Research objectives

To analyze the relationship between imaging features and the pathologic stage of HCC.

Research methods

There were 114 patients [75 with pathologic stage T1 (pT1) HCC and 39 with pathologic stage T2 (pT2) HCC] in this study. We reviewed each patient’s imaging features on preoperative gadoxetic acid-enhanced (EOB) MRI. These included: hyperintensity in unenhanced T2-weighted images, hypointensity in unenhanced T1-weighted images, arterial enhancement, corona enhancement, washout appearance, capsular appearance, hypointensity in the tumor tissue during the hepatobiliary (HB) phase, peritumoral hypointensity in the HB phase, hypointense rim in the HB phase, intratumoral fat, hyperintensity on diffusion-weighted imaging, hypointensity on apparent diffusion coefficient map, mosaic appearance, nodule-in-nodule appearance, and the margin. All of these patients underwent surgery and sections of their tumor specimens were analyzed microscopically by an experienced pathologist. Univariate and multivariate analyses were performed to identify predictors of microvascular invasion or satellite nodules.

Research results

We found that large tumor size (≥ 2.3 cm) and two MR findings, i.e., corona enhancement [odds ratio = 2.67; 95% confidence interval: 1.101-6.480) and peritumoral hypointensity in HB phase images (odds ratio = 2.203; 95% confidence interval: 0.961-5.049) were associated with high risk of pT2 HCC. The positive likelihood ratio was 6.25 (95% confidence interval: 1.788-21.845) and sensitivity of EOB-MRI for detecting pT2 HCC was 86.2% when two or three of these MRI features were present. Small tumor size and hypointense rim in the HB phase were regarded as benign features. Small HCCs with hypointense rim but not associated with aggressive features were mostly pT1 lesions (specificity, 100%).

Research conclusion

Imaging features on EOB-MRI could potentially be used to predict the pathologic stage of solitary HCC as pT1 or pT2.

Research perspectives

Imaging biomarkers of HCC are not yet well established. This study further identified imaging features of EOB-MRI that can be used to predict pathologic stage. This should be further validated in prospective studies. Research should be carried out to determine whether these MRI biomarkers help improve the clinical outcome of patients with HCC.