Published online Jul 21, 2020. doi: 10.3748/wjg.v26.i27.3938
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
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.
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.
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.
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.
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%.
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.
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.