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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Contrast-enhanced ultrasound Liver Imaging Reporting and Data System: Lights and shadows in hepatocellular carcinoma and cholangiocellular carcinoma diagnosis
Gianpaolo Vidili, Marco Arru, Giuliana Solinas, Diego Francesco Calvisi, Pierluigi Meloni, Assunta Sauchella, Davide Turilli, Claudio Fabio, Antonio Cossu, Giordano Madeddu, Sergio Babudieri, Maria Assunta Zocco, Giovanni Iannetti, Enza Di Lembo, Alessandro Palmerio Delitala, Roberto Manetti
Gianpaolo Vidili, Marco Arru, Diego Francesco Calvisi, Pierluigi Meloni, Assunta Sauchella, Davide Turilli, Claudio Fabio, Antonio Cossu, Giordano Madeddu, Sergio Babudieri, Alessandro Palmerio Delitala, Roberto Manetti, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari 07100, Italy
Giuliana Solinas, Department of Biomedical Sciences, Public Health-Laboratory of Biostatistics, University of Sassari, Sassari 07100, Italy
Maria Assunta Zocco, Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University, Rome 00168, Italy
Giovanni Iannetti, Enza Di Lembo, Ultrasound Unit, Ospedale S. Spirito, Pescara 65123, Italy
Author contributions: Vidili G designed the study, performed contrast-enhanced ultrasound examinations, biopsies, and the blinded review of cases, and wrote and revised the manuscript; Arru M performed the blinded review of the cases, collected and analysed the data, and participated in paper writing and review; Solinas G performed the statistical analysis and participated in the final draft; Calvisi DF collected and analysed the data, and participated in writing, review, and editing of the manuscript; Meloni P, Sauchella A, and Di Lembo E participated in collecting and preparing the data for the analysis; Turilli D and Fabio C performed computed tomography and magnetic resonance imaging scans and participated in data collection; Cossu A reviewed the pathology material; Madeddu G participated in data collection and writing the paper; Zocco MA and Iannetti G performed the external blinded review of the cases; Delitala AP and Babudieri S participated in data analysis and writing of the manuscript; Manetti R participated in writing and reviewing the final draft; all authors have read and agreed to the final version of the manuscript.
Supported by the Fondazione di Sardegna, No. FDS2019VIDILI; and the University of Sassari, No. FAR2019.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Azienda Ospedaliero Universitaria di Sassari and the Ethics Committee of Azienda Ospedaliero Universitaria di Cagliari (No. PG/2020/16814).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: Data presented in this study is available on request from the corresponding author.
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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Gianpaolo Vidili, MD, Assistant Professor, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 8 Viale San Pietro, Sassari 07100, Italy.
gianpaolovidili@uniss.it
Received: December 17, 2021
Peer-review started: December 17, 2021
First decision: January 27, 2022
Revised: February 10, 2022
Accepted: June 16, 2022
Article in press: June 16, 2022
Published online: July 21, 2022
Processing time: 212 Days and 17.4 Hours
BACKGROUND
Contrast-enhanced ultrasound (CEUS) is considered a secondary examination compared to computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of hepatocellular carcinoma (HCC), due to the risk of misdiagnosing intrahepatic cholangiocarcinoma (ICC). The introduction of CEUS Liver Imaging Reporting and Data System (CEUS LI-RADS) might overcome this limitation. Even though data from the literature seems promising, its reliability in real-life context has not been well-established yet.
AIM
To test the accuracy of CEUS LI-RADS for correctly diagnosing HCC and ICC in cirrhosis.
METHODS
CEUS LI-RADS class was retrospectively assigned to 511 nodules identified in 269 patients suffering from liver cirrhosis. The diagnostic standard for all nodules was either biopsy (102 nodules) or CT/MRI (409 nodules). Common diagnostic accuracy indexes such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed for the following associations: CEUS LR-5 and HCC; CEUS LR-4 and 5 merged class and HCC; CEUS LR-M and ICC; and CEUS LR-3 and malignancy. The frequency of malignant lesions in CEUS LR-3 subgroups with different CEUS patterns was also determined. Inter-rater agreement for CEUS LI-RADS class assignment and for major CEUS pattern identification was evaluated.
RESULTS
CEUS LR-5 predicted HCC with a 67.6% sensitivity, 97.7% specificity, and 99.3% PPV (P < 0.001). The merging of LR-4 and 5 offered an improved 93.9% sensitivity in HCC diagnosis with a 94.3% specificity and 98.8% PPV (P < 0.001). CEUS LR-M predicted ICC with a 91.3% sensitivity, 96.7% specificity, and 99.6% NPV (P < 0.001). CEUS LR-3 predominantly included benign lesions (only 28.8% of malignancies). In this class, the hypo-hypo pattern showed a much higher rate of malignant lesions (73.3%) than the iso-iso pattern (2.6%). Inter-rater agreement between internal raters for CEUS-LR class assignment was almost perfect (n = 511, k = 0.94, P < 0.001), while the agreement among raters from separate centres was substantial (n = 50, k = 0.67, P < 0.001). Agreement was stronger for arterial phase hyperenhancement (internal k = 0.86, P < 2.7 × 10-214; external k = 0.8, P < 0.001) than washout (internal k = 0.79, P < 1.6 × 10-202; external k = 0.71, P < 0.001).
CONCLUSION
CEUS LI-RADS is effective but can be improved by merging LR-4 and 5 to diagnose HCC and by splitting LR-3 into two subgroups to differentiate iso-iso nodules from other patterns.
Core Tip: This is a retrospective study to evaluate the accuracy of contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS) in correctly diagnosing hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis. CEUS LR-5 showed a 97.7% specificity for HCC with a low sensitivity (67.6%), while the CEUS LR-4 and 5 merged class showed a 93.9% sensitivity and 94.3% specificity for HCC. CEUS LR-M predicted ICC with a 91.3% sensitivity and 96.7% specificity. CEUS LR-3 predominantly included benign lesions (28.8% of malignancies) but was heterogeneous as the hypo-hypo pattern showed a higher rate of malignant lesions (73.3%) than the iso-iso pattern (2.6%).
