Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2018; 24(33): 3786-3798
Published online Sep 7, 2018. doi: 10.3748/wjg.v24.i33.3786
Differentiation of intrahepatic cholangiocarcinoma from hepatocellular carcinoma in high-risk patients: A predictive model using contrast-enhanced ultrasound
Li-Da Chen, Si-Min Ruan, Jin-Yu Liang, Zheng Yang, Shun-Li Shen, Yang Huang, Wei Li, Zhu Wang, Xiao-Yan Xie, Ming-De Lu, Ming Kuang, Wei Wang
Li-Da Chen, Si-Min Ruan, Jin-Yu Liang, Yang Huang, Wei Li, Zhu Wang, Xiao-Yan Xie, Ming-De Lu, Ming Kuang, Wei Wang, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Zheng Yang, Department of Pathology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Shun-Li Shen, Ming-De Lu, Ming Kuang, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: Chen LD, Ruan SM, Wang W, Xie XY, Lu MD, Kuang M designed the research; Chen LD, Ruan SM, Wang W, Liang JY, Huang Y performed the research; Chen LD and Ruan SM contributed equally to the design and preparation of this study and should be considered co-first authors; Li W, Wang Z contributed new reagents or analytical tools; Yang Z, Shen SL analyzed data; Chen LD, Ruan SM wrote the paper.
Supported by the National Nature Science Foundation of China, No. 81701719; the Guangdong Science and Technology Foundation, No. 2017A020215195; and the Guangdong Medical Scientific Research Foundation, No. A2016254.
Institutional review board statement: This study was approved by the Institutional Review Board of the First Affiliated Hospital of Sun Yat-Sen University.
Informed consent statement: Informed consent was obtained from each patient.
Conflict-of-interest statement: The authors have declared no conflicts of interest.
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/
Correspondence to: Wei Wang, MD, PhD, Associate Professor, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080, Guangdong Province, China. wangw73@mail.sysu.edu.cn
Telephone: +86-20-87765183 Fax: +86-20-87765183
Received: May 7, 2018
Peer-review started: May 7, 2018
First decision: May 16, 2018
Revised: June 30, 2018
Accepted: July 16, 2018
Article in press: July 16, 2018
Published online: September 7, 2018
Processing time: 122 Days and 22.5 Hours
ARTICLE HIGHLIGHTS
Research background

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant epithelial cancer originating from bile ducts with cholangiocyte differentiation. In recent years, chronic cirrhosis and viral hepatitis have been recognized as important risk factors for ICC development. ICC has been increasingly found in patients with cirrhosis, and distinguishing between ICC and hepatocellular carcinoma (HCC) is a major clinical issue because the management and prognosis of these conditions differ significantly.

Research motivation

The contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS®) sets the specific category of LR-M for distinguishing ICC from HCC, but the diagnostic dilemma remains unresolved. Additionally, no study has validated the performance of LR-M as the differential diagnostic criterion for ICC and HCC.

Research objectives

To identify important imaging predictors of ICC on CEUS, to develop a novel diagnostic nomogram incorporating clinical, CEUS and laboratory characteristics that could be used to accurately predict the risk of ICC in high-risk patients and to compare the nomogram with modified CEUS LI-RADS.

Research methods

This retrospective study consisted of 88 consecutive high-risk patients with ICC and 88 high-risk patients with HCC selected by propensity score matching between May 2004 and July 2016. Patients were assigned to two groups, namely, a training set and validation set, at a 1:1 ratio. A CEUS score for diagnosing ICC was generated based on significant CEUS features. Then, a nomogram based on the CEUS score was developed, integrating the clinical data. The performance of the nomogram was then validated and compared with that of the LR-M of the CEUS LI-RADS.

Research results

The most useful CEUS features for ICC were as follows: rim enhancement (64.5%), early washout (91.9%), intratumoral vein (58.1%), obscure boundary of intratumoral non-enhanced area (64.5%), and marked washout (61.3%, all P < 0.05). In the validation set, the area under the curve (AUC) of the CEUS score (AUC = 0.953) for differentiation between ICC and HCC were improved compared to the LI-RADS (AUC = 0.742) (P < 0.001). When clinical data were added, the CEUS score nomogram was superior to the LI-RADS nomogram (AUC: 0.973 vs 0.916, P = 0.036, NRI: 0.077, IDI: 0.152). Subgroup analysis demonstrated that the CEUS score model was notably improved compared to the LI-RADS in under 5.0 cm tumors (P < 0.05) but not improved in tumors under 3.0 cm (P > 0.05).

Research conclusions

A CEUS score for predicting ICC consisted of more detailed CEUS features (rim enhancement, early washout, intratumoral vein, obscure boundary of intratumoral non-enhanced area, and marked washout) was constructed.

The diagnostic performance of the CEUS score (AUC = 0.953) for differentiation between ICC and HCC was improved compared to the LR-M of LI-RADS (AUC = 0.742) (P < 0.001). A CEUS score nomogram that added the clinical risk factors was superior to the LI-RADS nomogram (AUC: 0.973 vs 0.916, P = 0.036, NRI: 0.077, IDI: 0.152). The CEUS score predictive model was notably improved compared to the LI-RADS in ≤ 5.0 cm tumors (P < 0.05) but not improved in tumors ≤ 3.0 cm (P > 0.05).

Research perspectives

The CEUS predictive model for differentiation between ICC and HCC in high-risk patients had improved discrimination and clinical usefulness compared to the CEUS LI-RADS.