Published online Dec 14, 2020. doi: 10.3748/wjg.v26.i46.7325
Peer-review started: August 6, 2020
First decision: October 18, 2020
Revised: October 31, 2020
Accepted: November 9, 2020
Article in press: November 9, 2020
Published online: December 14, 2020
Combined hepatocellular-cholangiocarcinoma (CHC) is a rare type of primary liver cancer. Due to its complex histopathological characteristics, the imaging features of CHC may overlap with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).
The contrasted-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) released by the American College of Radiology has been reported to be effective for the diagnosis of HCC. However, CHC lesions meeting the criteria for LR-5 classification may compromise the high specificity of LR-5 for the diagnosis of HCC if we only take the imaging features into consideration. Serum biomarkers, especially alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9), have been shown to be helpful in the diagnosis of CHC. However, whether combining CEUS LI-RADS with serum biomarkers is helpful for differentiating CHC from HCC and ICC in at-risk patients has not been fully evaluated.
The purpose of this study was to investigate whether the combination of CEUS LI-RADS and serum biomarkers is helpful for differentiating CHC from HCC and ICC in patients with chronic liver disease.
Patients with histologically confirmed CHC, ICC and HCC with chronic liver disease between January 2016 and December 2019 were enrolled in this retrospective case control study. HCC patients were finally enrolled after one-to-two (CHC:HCC = 1:2) propensity score matching by tumor size, age and sex. Differences in quantitative variables were tested by the independent sample t-test. The rates of imaging characteristics were compared by using the χ2 test or Fisher’s exact test. Receiver operating characteristic curve analysis was used to investigate the potential of CEUS LI-RADS and serum tumor markers for differentiating CHC from HCC and ICC.
After propensity score matching, 134 patients (mean age of 51.4 ± 9.4 years, 108 men) were enrolled, including 35 CHC, 29 ICC and 70 HCC patients. Based on the CEUS LI-RADS classification, 74.3% (26/35) and 25.7% (9/35) of CHC lesions were assessed as LR-M and LR-5, respectively. The rates of elevated AFP and CA19-9 levels in CHC patients were 51.4% and 11.4%, respectively. Simultaneous elevation of AFP and CA19-9 was found in 8.6% (3/35) of CHC patients. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and AUC of the aforementioned diagnostic criteria for discriminating CHC from HCC and ICC were 40.0%, 89.9%, 58.3%, 80.9%, 76.9% and 0.649, respectively. When the reported prevalence rate of CHC (0.4%-14.2%) was taken into account, the PPV and NPV were revised to 1.6%-39.6% and 90.1%-99.7%, respectively.
CHCs are more likely to be classified as LR-M than LR-5 by CEUS LI-RADS. The combination of the CEUS LI-RADS classification with serum tumor markers shows high specificity but low sensitivity for the diagnosis of CHC. Moreover, CHC could be confidently excluded with a high NPV.
The imaging features of CHC are complicated due to its complex histopathological characteristics. In addition, biopsy may misguide the correct diagnosis of CHC due to sampling error or tissue insufficiency. This study investigated the diagnostic value of the CEUS LI-RADS classification combined with serological tumor markers in differentiating CHC from HCC and ICC. The results showed that the combined diagnostic criteria had high specificity and NPV but low sensitivity for the diagnosis of CHC. These findings could help radiologists and clinical investigators confidently exclude CHC lesions in the clinical setting.