Differentiation between hepatocellular carcinoma and intrahepatic cholangiocarcinoma using contrast-enhanced ultrasound: A systematic review and meta-analysis

Abstract

AIM: To explore the diagnostic ability of contrast-enhanced ultrasound (CEUS) in distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). MATERIALS AND METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for studies reporting the diagnostic accuracy of CEUS in differentiating ICC from HCC. The diagnostic ability of CEUS was assessed based on the pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the curve (AUC) with 95% confidence intervals (CIs). The methodologic quality was assessed by the QUADAS-2 tool. Subgroup analyses, meta-regression and investigation of publication bias were performed to identify the source of heterogeneity. RESULTS: A total of eight studies were included, consisting of 1,116 patients with HCC and 529 with ICC. The general diagnostic performance of CEUS in distinguishing ICC and HCC were as follows: pooled sensitivity, 0.92 (95% CI: 0.84–0.96); pooled specificity, 0.87 (95% CI: 0.79–0.92); pooled PLR, 7.1 (95% CI: 4.1–12.0); pooled NLR, 0.09 (95% CI: 0.05–0.19); pooled DOR, 76 (95% CI: 26–220) and AUC, 0.95(95% CI: 0.93–0.97). Different liver background may be a potential factor that influenced the diagnostic accuracy of CEUS according to the subgroup analysis, with the pooled DOR of 89.67 in the mixed liver background group and 46.87 in the cirrhosis group, respectively. Six informative CEUS features that may help differentiate HCC from ICC were extracted. The three CEUS features favoring HCC were arterial phase hyperenhancement(APHE), mild washout and late washout (>60s); the three CEUS favoring ICC were arterial rim enhancement, marked washout and early washout(<60s). No potential publication bias was observed. CONCLUSION: CEUS showed great diagnostic ability in differentiating ICC from HCC, which may be promising for noninvasive evaluation of these diseases.

Conventional, functional and radiomics assessment for intrahepatic cholangiocarcinoma

“…ICC exhibits lesser enhancement in arterial phase with early (< 60 s) and prominent washout compared to HCC [ 40 – 54 ]. Chen et al demonstrated that the pooled sensitivity of CEUS in differentiating ICC from HCC was 0.92 and the pooled specificity was 0.87 [ 42 ].

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Update on the Applications of Radiomics in Diagnosis, Staging, and Recurrence of Intrahepatic Cholangiocarcinoma

“…As shown in international guidelines, the differential diagnosis between HCC and ICC can be challenging, especially in non-cirrhotic patients, where the typical radiological pictures of mass-forming ICC might be very similar to pictures of HCC enhancement pattern, requiring liver biopsy to achieve the correct diagnosis [ 85 ]. CEUS achieved a reliable sensitivity in differentiating ICC from HCC of 0.92 with a pooled specificity of 0.87 [ 86 , 87 ]. Considering that the diagnostic performance of CEUS is very changeable as the diagnostic technique is operator-dependent, ultrasomics surely could make the US exams more repeatable and reliable, standardizing the technique; in fact, in the comparison studies between radiologists and ultrasomics model performance, the latter achieved a better sensitivity and global accuracy [ 87 ].…”

“…CEUS achieved a reliable sensitivity in differentiating ICC from HCC of 0.92 with a pooled specificity of 0.87 [ 86 , 87 ]. Considering that the diagnostic performance of CEUS is very changeable as the diagnostic technique is operator-dependent, ultrasomics surely could make the US exams more repeatable and reliable, standardizing the technique; in fact, in the comparison studies between radiologists and ultrasomics model performance, the latter achieved a better sensitivity and global accuracy [ 87 ]. Ultrasomics has been proven to be useful in the early diagnosis, preoperative grading prediction, therapeutic efficacy evaluation, and prognosis evaluation of several tumors [ 88 , 89 , 90 , 91 , 92 , 93 ].…”

Preoperative differentiation of hepatocellular carcinoma with peripheral rim-like enhancement from intrahepatic mass-forming cholangiocarcinoma on contrast-enhanced MRI

“…The distinction between HCCs and IMCCs is crucial for clinicians because the prognosis and treatment options differ considerably between the two types ( 19 ). Thus, a noninvasive way to distinguish iCCA and HCC preoperatively is needed ( 27 ). Nowadays, contrast-enhanced MRI is widely used for preoperative diagnoses and evaluation of liver tumors.…”