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
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) differ in treatment and prognosis, warranting an effective differential diagnosis between them. The LR-M category in the contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) was set up for lesions that are malignant but not specific to HCC. However, a substantial number of HCC cases in this category elevated the diagnostic challenge.

AIM

To investigate the possibility and efficacy of differentiating ICC from HCC classified in the LR-M category according to the CEUS LI-RADS.

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 (ROC) curve analysis was used to investigate the possibility of LR-M criteria and serum tumor markers in differentiating ICC from LR-M HCC.

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 (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) had 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 ROC 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%.

CONCLUSION

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 strong predictor of ICC rather than LR-M HCC. Early washout and marked washout have limited value for the differentiation between the two entities.

Keywords: Diagnosis, Contrast enhanced ultrasound, Hepatocellular carcinoma, Intrahepatic cholangiocarcinoma, Liver imaging reporting and data system

Core tip: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) differ in treatment and prognosis, warranting an effective differential diagnosis between them. The LR-M category in the contrast-enhanced ultrasound liver imaging reporting and data system was set up for lesions that are malignant but not specific to HCC. Our study demonstrated that rim arterial phase hyperenhancement (APHE) is a key predictor for differentiating ICC from LR-M HCC, whereas early washout and marked washout have limited value for differentiating them. Rim APHE plus elevated carbohydrate antigen 19-9 and normal alpha fetoprotein is a strong predictor of ICC rather than LR-M HCC.