Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2020; 26(27): 3938-3951
Published online Jul 21, 2020. doi: 10.3748/wjg.v26.i27.3938
Can contrast enhanced ultrasound differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma?
Jia-Yan Huang, Jia-Wu Li, Wen-Wu Ling, Tao Li, Yan Luo, Ji-Bin Liu, Qiang Lu
Jia-Yan Huang, Jia-Wu Li, Wen-Wu Ling, Yan Luo, Qiang Lu, Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Tao Li, Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Ji-Bin Liu, Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, United States
Author contributions: Lu Q, Luo Y, and Liu JB designed the research; Li JW and Ling WW performed the research; Huang JY, Li T, and Lu Q contributed to the analytical tools; Huang JY, Li JW, and Lu Q analyzed the data; Huang JY wrote the paper; Lu Q, Luo Y, and Liu JB revised and edited the manuscript.
Supported by National Natural Science Foundation of China, No. 81571697; Science and Technology Department of Sichuan Province, No. 2018FZ0044; 1.3.5 Project for Disciplines of Excellence, West China Hospital of Sichuan University, No. ZYJC18008.
Institutional review board statement: This study was reviewed and approved by West China Hospital of Sichuan University.
Informed consent statement: All patients gave informed consent to the study.
Conflict-of-interest statement: The authors have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Qiang Lu, MD, Professor, Department of Medical Ultrasound, West China Hospital of Sichuan University, No. 37, Guoxue Lane, Chengdu 610041, Sichuan Province, China. luqiang@wchscu.cn
Received: March 2, 2020
Peer-review started: March 2, 2020
First decision: April 25, 2020
Revised: May 9, 2020
Accepted: July 4, 2020
Article in press: July 4, 2020
Published online: July 21, 2020
Processing time: 141 Days and 10.3 Hours
ARTICLE HIGHLIGHTS
Research background

Liver cancer is the sixth most common cancer worldwide and the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) account for the majority of all primary liver cancers and differ in treatment and prognosis.

Research motivation

Contrast-enhanced ultrasound (CEUS) has been recommended and widely used for the characterization of focal liver lesions. However, the value of CEUS in differentiating between ICC and HCC remains controversial. The CEUS liver imaging reporting and data system (LI-RADS) released by the American College of Radiology has been developed for standardizing CEUS criteria for the diagnosis of focal liver lesions. In the criteria, the LR-M category represents malignancies but is not specific to HCC. Of note, the presence of a substantial number of HCCs in this category elevates the difficulty in the differential diagnosis between ICC and HCC, and the efficacy of LR-M features for the differentiation between them has not yet been fully evaluated.

Research objectives

The purpose of this study was to investigate the possibility and efficacy of differentiating ICC from HCC classified in the LR-M category according to the CEUS LI-RADS.

Research methods

Patients with complete CEUS records together with pathologically confirmed ICC and LR-M HCC (HCC classified in the CEUS LI-RADS LR-M category) between January 2015 and October 2018 were included in this retrospective study. Each ICC was assigned a category as per the CEUS LI-RADS. The enhancement pattern, washout timing, and washout degree between the ICC and LR-M HCC were compared using the χ2 test. Logistic regression analysis was used for prediction of ICC. Receiver operating characteristic curve analysis was used to investigate the possibility of LR-M criteria and serum tumor markers in differentiating ICC from LR-M HCC.

Research results

A total of 228 nodules (99 ICCs and 129 LR-M HCCs) in 228 patients were included. The mean sizes of ICC and LR-M HCC were 6.3 ± 2.8 cm and 5.5 ± 3.5 cm, respectively (P = 0.03). Peripheral rim-like arterial phase hyperenhancement (rim APHE) was detected in 50.5% (50/99) of ICCs vs 16.3% (21/129) of LR-M HCCs (P < 0.001). Early washout was found in 93.4% (93/99) of ICCs vs 96.1% (124/129) of LR-M HCCs (P > 0.05). Marked washout was observed in 23.2% (23/99) of ICCs and 7.8% (10/129) of LR-M HCCs (P = 0.002), while this feature did not show up alone either in ICC or LR-M HCC. Homogeneous hyperenhancement was detected in 15.2% (15/99) of ICCs and 37.2% (48/129) of LR-M HCCs (P < 0.001). The logistic regression showed that rim APHE, carbohydrate antigen 19-9 (CA 19-9), and alpha fetoprotein (AFP) exhibited significant correlations with ICC (r = 1.251, 3.074, and -2.767, respectively; P < 0.01). Rim APHE presented the best enhancement pattern for diagnosing ICC, with an area under the receiver operating characteristic curve (AUC) of 0.70, sensitivity of 70.4%, and specificity of 68.8%. When rim hyperenhancement was coupled with elevated CA 19-9 and normal AFP, the AUC and sensitivity improved to 0.82 and 100%, respectively, with specificity decreasing to 63.9%.

Research conclusions

This study illustrated that rim APHE is a key predictor for differentiating ICC from LR-M HCC. Rim APHE plus elevated CA 19-9 and normal AFP is a predictor of ICC rather than LR-M HCC. Early washout and marked washout have limited value for the differentiation between the two entities.

Research perspectives

Rim APHE is a key predictor for differentiating ICC from LR-M HCC, and rim APHE plus elevated CA 19-9 and normal AFP is a predictor of ICC rather than LR-M HCC. The reference values of early washout (< 60 s) and marked washout within 120 s in the LR-M category are needed to further refine the CEUS LI-RADS criteria to avoid unnecessary biopsy.