To evaluate the diagnostic value of ultrasound elastography (USE) for characterizing hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

The protocol was pre-registered a priori at ( https://osf.io/namvk/ ). Using PubMed, Web of Science, Embase, and Cochrane Library, we found studies up to April 20, 2024 by searching HCC, ICC, and USE as keywords. Parameters of USE were directly compared between HCC and ICC patients using random-effects bivariate model on STATA 17.0, MedCalc 20.0, and Psychometrica. Trim & fill method and sensitivity analysis were also performed.

Eighteen studies were included with 1057 patients, consisting of 863 HCC lesions, 188 ICC lesions, and 6 mixed lesions. The pooled Emean values of HCC and ICC were 28.3 (CI = 19.8 to 36.8) and 44.0 (CI = 20.9 to 67.2). HCC tumors were 34.3% softer than ICC while peritumoral tissue in HCC lesions was 75% stiffer than ICC lesions based on Emean. The strain value index (tumoral-to-peritumoral ratio) in HCC patients was 49.4% less than that of ICC patients. USE demonstrated a pool sensitivity of 87% (CI = 73-95%), specificity of 82% (CI = 65-92%), positive likelihood ratio of 4.8 (CI = 2.2 to 10.3), negative likelihood ratio of 0.16 (CI = 0.07 to 0.37), and diagnostic odds ratio of 31 (CI = 7 to 127) in differentiation of ICC from HCC.

By evaluating tumoral and pre-tumoral stiffness, along with strain value index, USE may provide a valuable quantitative diagnostic tool for accurately differentiating HCC and ICC.

Background: Contrast-enhanced ultrasound (CEUS) has become the preferred method for many clinicians in evaluating focal liver lesions (FLLs) initially identified through standard ultrasound. However, in clinical practice, certain lesions may deviate from the typical enhancement patterns outlined in EFSUMB guidelines. Methods: This study aims to assess FLLs that remained inconclusive or misdiagnosed after CEUS evaluation, spanning eight years of single-center experience. Following CEUS, all FLLs underwent secondary imaging (CT, MRI) or histopathological analysis for diagnostic confirmation. Results: From the initial 979 FLLs, 350 lesions (35.7%) were either inconclusive or misdiagnosed by CEUS, with hepatocellular carcinoma (HCC) and liver metastases constituting the majority of these cases. The most frequent enhancement pattern in inconclusive lesions at CEUS was hyper-iso-iso. Factors such as advanced liver fibrosis, adenomas, and cholangiocarcinoma were significantly associated with higher rates of diagnostic inaccuracies. Conclusions: Advanced liver fibrosis, adenomas, and cholangiocarcinoma were significantly associated with increased diagnostic challenges, emphasizing the need for supplementary imaging techniques.

To enhance the accuracy of hepatocellular carcinoma (HCC) diagnosis using contrast-enhanced (CE) US, the American College of Radiology developed the CEUS Liver Imaging Reporting and Data System (LI-RADS). However, the system still exhibits limitations in distinguishing between HCC and non-HCC lesions.

To investigate the viability of employing machine learning methods based on quantitative parameters of contrast-enhanced ultrasound for distinguishing HCC within LR-M nodules.

This retrospective analysis was conducted on pre-treatment CEUS data from liver nodule patients across multiple centers between January 2013 and June 2022. Quantitative analysis was performed using CEUS images, and the machine learning diagnostic models based on quantitative parameters were utilized for the classification diagnosis of LR-M nodules. The performance of the model was assessed using the area under the receiver operating characteristic curve (AUC) and compared with the performance of four radiologists.

The training and internal testing datasets comprised 168 patients (median age, 53 years [IQR, 18 years]), while the external testing datasets from two other centers included 110 patients (median age, 54 years [IQR, 16 years]). In the internal independent test set, the top-performing Random Forest model achieved an AUC of 0.796 (95%CI: 0.729-0.853) for diagnosing HCC. This model exhibited a sensitivity of 0.752 (95%CI: 0.750-0.755) and a specificity of 0.761 (95%CI: 0.758-0.764), outperforming junior radiologists who achieved an AUC of 0.619 (95%CI: 0.543-0.691, p < .01) with sensitivity and specificity of 0.716 (95%CI: 0.713-0.718) and 0.522 (95%CI: 0.519-0.526), respectively.

Significant differences in contrast-enhanced ultrasound quantitative parameters are observed between HCC and non-HCC lesions. Machine learning models leveraging these parameters effectively distinguish HCC categorized as LR-M, offering a valuable adjunct for the accurate classification of liver nodules within the CEUS LI-RADS framework.

Chemokines play a crucial role in the pathogenesis of patients with hepatocellular carcinoma (HCC). The expression levels of interferon-γ-induced protein-10 (CXCL10) and macrophage inflammatory protein-3α (MIP-3a) were investigated to clarify their clinical significance in HCC. The protein levels of CXCL10 and MIP-3a in the serum of 105 HBV-associated HCC patients, 50 patients with liver cirrhosis (LC), 50 patients with chronic hepatitis B (CHB) and 50 healthy donors (HC) were detected by liquid chip technology (Luminex) or ELISA. In addition, their mRNA levels were also determined in liver cancer and adjacent cancer tissue (paracancer; ParaCa) from 65 HCC patients. The online database UALCAN was used to analyze the association between CXCL10 and pathological manifestations of liver cancer. In addition, the diagnostic value of CXCL10/MIP-3a and AFP in HCC patients was determined by analyzing the Receiver Operating Characteristic Curve (ROC). The protein concentrations of CXCL10 and MIP-3a were significantly higher in the HCC group than in the LC, CHB and HC groups. CXCL10 in sera and liver cancer tissues is significantly positively correlated with ALT, but no significance between CXCL10 in ParaCa tissues and sera-ALT. Their mRNA is significantly higher in cancer tissues than in ParaCa tissues. The areas under the ROC curve of CXCL10, MIP-3a, CXCL10 and MIP-3a combined and AFP were 0.9169, 0.9261, 0.9299 and 0.7880, respectively. Elevated chemokines CXCL10 and MIP-3a in HCC patients may be associated with the clinical manifestation of HCC and could be a potential molecular marker for prognostic evaluation or a therapeutic target for HCC.

The aim of the study was to explore the clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous microwave coagulation therapy (PMCT) for advanced hepatocellular carcinoma (HCC).

Eighty-three advanced HCC patients were divided into the experimental group (TACE + PMCT, 57 cases) and the control group (TACE alone, 26 cases). They received TACE treatment first, and computed tomography (CT) or hepatic artery angiography was performed 3 - 4 weeks after each treatment. Based on the comprehensive evaluation of iodine oil deficiency, fistula recanalization, residual lesions, and lesion progression, TACE or PMCT treatment was selectively performed, and three consecutive treatments were considered as one treatment cycle.

The experimental group had a response rate (RR) of 49.1%, and the control group had a RR of 38.4%. The reduction rate of alpha-fetoprotein (AFP) in the experimental group was significantly higher than the control group (P < 0.05). The cumulative survival rates in the experimental at 1-, 1.5-, and 2-year post-treatment were higher than the control group. The cumulative recurrence and metastasis rates in the experimental at 1.5-, and 2-year post-treatment were significantly lower than those in the control group (P < 0.05). In addition, there were no significant differences in treatment-related complications in the two groups.

The combined treatment of TACE and PMCT for advanced HCC is a safe, feasible, and effective treatment method, prolonging the survival time, and reducing the recurrence and metastasis rate, without increased toxic and side effects.

Non-invasive differential diagnosis between hepatocellular carcinoma (HCC) and other liver cancer (i.e. cholangiocarcinoma or metastasis) is highly challenging and definitive diagnosis still relies on histological exam. The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features. Dynamic contrast-enhanced ultrasound (DCEUS) with standardized software could help to overcome these obstacles, providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion.

To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules.

A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned.

Rise time was significantly higher in HCC patients with a standardized mean difference (SMD) of 0.83 (95%CI: 0.48-1.18). Similarly, other statistically significant parameters were mean transit time local with a SMD of 0.73 (95%CI: 0.20-1.27), peak enhancement with a SMD of 0.37 (95%CI: 0.03-0.70), area wash-in area under the curve with a SMD of 0.47 (95%CI: 0.13-0.81), wash-out area under the curve with a SMD of 0.55 (95%CI: 0.21-0.89) and wash-in and wash-out area under the curve with SMD of 0.51 (95%CI: 0.17-0.85). SMD resulted not significant in fall time and wash-in rate, but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma.

DCEUS could improve non-invasive diagnosis of HCC, leading to less liver biopsy and early treatment. This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results.

Diagnosis of cholangiocarcinoma (CCA) can be challenging due to unclear imaging criteria and difficulty obtaining adequate tissue biopsy. Although serum cancer antigen 19-9 and carcinoembryonic antigen have been proposed as potential diagnostic aids, their use remains limited by insufficient sensitivity and specificity. This exploratory analysis aimed to identify individual- and combinations of serum biomarkers to distinguish CCA from hepatocellular carcinoma (HCC) and chronic liver disease (CLD) controls using samples from a published study.

This prospective, multicenter, case-control study included patients aged ≥18 years at high-risk of HCC. Serum and ethylene diamine tetraacetic acid-plasma samples were collected prior to any treatment and confirmed diagnosis of HCC or CCA. Fourteen biomarkers (measured by electrochemiluminescence immunoassays or enzyme-linked immunosorbent assays) were subjected to univariate analysis and 13 included in a multivariate analysis (per selected combinations and exhaustive search).

Overall, 55 CCA, 306 HCC, and 733 CLD control samples were analyzed. For distinguishing CCA from HCC, alpha-fetoprotein and matrix metalloproteinase-2 (MMP-2) showed the best individual performance (area under the curve (AUC) 86.6% and 84.4%, respectively); tissue inhibitor of metalloproteinase-1 (TIMP-1) was most able to distinguish CCA from CLD (AUC 94.5%) and from HCC  +  CLD (AUC 88.6%). The combination of MMP-2 and TIMP-1 was the best-performing two-marker panel, with AUC >90% for all comparisons.

MMP-2 and TIMP-1 are promising biomarkers that could support differential diagnosis of CCA. Incorporating these assays into the diagnostic algorithm could provide additional diagnostic information in a non-invasive, rapid manner, and could supplement existing diagnostic methods.

Purpose: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are primary liver cancers with different therapeutic methods and prognoses. This study aims to investigate the ultrasonography and enhanced computed tomography (CT) features of these cancers and improve the early diagnosis rate. Methods: We retrospectively analyzed the clinical and imaging data of 319 patients diagnosed with HCC and 124 patients diagnosed with ICC, confirmed by pathology. Results: A total of 443 patients were eligible in this study. From the perspective of clinical data, between HCC and ICC patients existed significant differences in age, gender, hepatic background, serum tumor markers of AFP and CA19.9, chronic hepatitis B/C and lymph node infiltration (p<0.05), but not in tumor size, microvascular invasion, serum tumor markers of CEA and CA125 (P>0.05). With respect to ultrasonography features, HCC patients had a higher proportion than ICC patients in splenomegaly (p=0.001), while ICC patients had a higher proportion than HCC patients in absence/not rich vascularity and intrahepatic bile duct dilatation (p<0.05). With respect to CT features, HCC patients were significantly different from ICC patients in the three-phase enhanced CT value mean, enhanced intensity and homogeneity of nodules (P<0.05). A multivariate logistic regression analysis was performed to further clarify the correlation of these indices. However, only age≤60 years (OR=1.861, P=0.045), male (OR=3.850, P<0.001), AFP>7ng/ml (OR=0.119, P<0.001), lymph node infiltration (OR=5.968, P<0.001), intrahepatic bile duct dilatation (OR=2.414, P=0.04), splenomegaly (OR=0.081, P<0.001), rim APHE (OR=3.109, P=0.002), and iso- or hyper enhancement (OR=0.188, P<0.001) were independent risk factors. Conclusions: While there are overlapping ultrasonography and CT features between HCC and ICC, the integration of tumor markers and specific imaging characteristics can be beneficial in distinguishing between the two.

Intrahepatic cholangiocarcinoma (ICC) is a rare, heterogeneous, highly lethal tumor of the biliary tract. Due to the lack of effective treatments, an early identification of ICC is essential to achieve the best outcome in terms of therapy and prognosis aiming for a curative intent. ICC may arise on a normal liver or with an underlying liver disease, making the diagnosis more difficult and complex. Contrast-enhancement ultrasound (CEUS) is an accurate procedure able to detect ICC-specific contrast vascular pattern, and thus facilitating the correlation between radiological and histopathological findings with high specificity and sensitivity. CEUS has been shown to have a high diagnostic potential in the diagnosis of ICC thanks to the possibility of studying in real time the intralesional microcirculation and evaluating the precocity of the enhancement of the lesion during the arterial phase. All these features allow to differentiate the ICC from hepatocarcinoma (HCC) with high sensitivity and specificity. Furthermore, CEUS is a rapid, non-invasive, non-nephrotoxic or non-allergenic tool. The only limitations CEUS may have are related to the disease site and patient characteristics (obesity) and compliance, including the operator's experience. A clinical evaluation of the patient, together with tumor markers and biochemical tests assessment, to differentiate ICC from HCC are highly suggested.