Liver stiffness in hepatocellular carcinoma and chronic hepatitis patients: Hepatitis B virus infection and transaminases should be considered.

BACKGROUND: Liver condition is a crucial prognostic factor for patients with hepatocellular carcinoma (HCC), but a convenient and comprehensive method to assess liver condition is lacking. Liver stiffness (LS) measured by two-dimensional shear wave elastography may help in assessing liver fibrosis and liver condition. Chronic hepatitis B (CHB) is an important risk factor for HCC progression, but LS was found to be less reliable in assessing liver fibrosis following hepatitis viral eradication. We hypothesize that the status of hepatitis virus infection would affect the accuracy of LS in assessing the liver condition. AIM: To test the feasibility and impact factors of using LS to assess liver condition in patients with HCC and CHB. METHODS: A total of 284 patients were retrospectively recruited and classified into two groups on the basis of serum CHB virus hepatitis B virus (HBV)-DNA levels [HBV-DNA ≥ 100.00 IU/mL as Pos group (n = 200) and < 100.00 IU/mL as Neg group (n = 84)]. Correlation analyses and receiver operating characteristic analyses were conducted to evaluate the relationship between LS and liver condition. RESULTS: A significant correlation was found between LS and most of the parameters considered to have the ability to evaluate liver condition (P < 0.05). When alanine aminotransferase (ALT) concentrations were normal (≤ 40 U/L), LS was correlated with liver condition indices (P < 0.05), but the optimal cutoff of LS to identify a Child-Pugh score of 5 was higher in the Neg group (9.30 kPa) than the Pos group (7.40 kPa). When ALT levels were elevated (> 40 U/L), the correlations between LS and liver condition indices were not significant (P > 0.05). CONCLUSION: LS was significantly correlated with most liver condition indices in patients with CHB and HCC. However, these correlations varied according to differences in HBV-DNA and transaminase concentrations.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound.

BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) represent the predominant histological types of primary liver cancer, comprising over 99% of cases. Given their differing biological behaviors, prognoses, and treatment strategies, accurately differentiating between HCC and ICC is crucial for effective clinical management. Radiomics, an emerging image processing technology, can automatically extract various quantitative image features that may elude the human eye. Reports on the application of ultrasound (US)-based radiomics methods in distinguishing HCC from ICC are limited. AIM: To develop and validate an ultrasomics model to accurately differentiate between HCC and ICC. METHODS: In our retrospective study, we included a total of 280 patients who were diagnosed with ICC (n = 140) and HCC (n = 140) between 1999 and 2019. These patients were divided into training (n = 224) and testing (n = 56) groups for analysis. US images and relevant clinical characteristics were collected. We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models. We compared the diagnostic performances of these ultrasomics models with that of radiologists. RESULTS: Four distinct ultrasomics models were constructed, with the number of selected features varying between models: 13 features for the US model; 15 for the contrast-enhanced ultrasound (CEUS) model; 13 for the combined US + CEUS model; and 21 for the US + CEUS + clinical data model. The US + CEUS + clinical data model yielded the highest area under the receiver operating characteristic curve (AUC) among all models, achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort. This performance exceeded even the most experienced radiologist (AUC = 0.964). The AUC for the US + CEUS model (training cohort AUC = 0.964, test cohort AUC = 0.955) was significantly higher than that of the US model alone (training cohort AUC = 0.822, test cohort AUC = 0.816). This finding underscored the significant benefit of incorporating CEUS information in accurately distinguishing ICC from HCC. CONCLUSION: We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC, which outperformed experienced radiologists.

Using four-point subcutaneous injection of lymphatic contrast-enhanced ultrasound to diagnose lymphedema of lower extremity.

Background: The diagnosis of lymphedema primarily relies on the clinical symptoms, signs, medical history and imaging. Objective lymphatic imaging helps improving the diagnosis of lymphedema. This study aimed to develop an effective imaging tool to diagnose lymphedema. Methods: This is a single-center retrospective study. From September 2022 to November 2023, we enrolled thirty-two patients, involving 40 lower extremities who underwent lymphatic contrast-enhanced ultrasound (CEUS) following a subcutaneous injection of contrast agent at four points in the First Affiliated Hospital of Sun Yat-sen University. Cohen's kappa value, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. Lymphoscintigraphy was the reference standard. Results: Successful lymphatic-CEUS detection was defined as the situation that lymphatic drainage of medial or lateral lower limbs were observed. The successful detection rate was 100% (40 of 40). The diagnosis of lymphedema was based on the presence of either medial or lateral lymphatic obstructions, or subcutaneous lymphatic enhancement. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for diagnosing lymphedema by lymphatic-CEUS were as follows: 91.2% (31 of 34), 100% (6 of 6), 100% (31 of 31), 66.7% (6 of 9) and 92.5% (37 of 40), respectively. The Cohen's Kappa value was 0.756. The area under the receiver operating characteristic curve (AUC) for the subcutaneous injection of four-point lymphatic-CEUS was 0.956. Conclusions: This study put forward a novel four-point lymphatic-CEUS method to detect the functions of the lymphatics of lower extremities and established a lymphatic-CEUS standard for diagnosing lymphedema of lower extremities. Four-point lymphatic-CEUS is a considerable option for diagnosing lymphedema of lower extremities.

Feasibility and Measurement Value of Pancreatic 2-D Shear Wave Elastography in Healthy Adults: Evaluation, Influencing Factors, Reference Range, Measurement Stability and Reproducibility.

OBJECTIVE: The present study was aimed at assessing the success rate and measurement value, determining the influencing factors and reference range and examining the intra-operator stability and inter-operator reproducibility of pancreatic 2-D shear wave elastography (SWE) measurement in healthy adults. METHODS: In 2022, 387 healthy adults were prospectively recruited. Logistic regression and linear regression analyses were used to explore the factors influencing the success rate and the measurement value of pancreatic 2-D SWE measurement, respectively. A two-sided 95% reference range was estimated accordingly. The intraclass correlation coefficient was calculated to evaluate the intra-operator stability and inter-operator reproducibility of the pancreatic 2-D SWE measurement. RESULTS: The pancreatic body (89.6%) bore the highest while the tail (72.8%) bore the lowest success rate of pancreatic 2-D SWE measurement. Sex and body mass index (BMI) were the independent factors influencing measurement success rate in all three parts of the pancreas. Mean measurement values (Emean) were not the same in the three parts of the pancreas of the same participant. BMI and image depth were the independent factors influencing Emean in the pancreatic body, while region of interest depth and BMI were the only independent factors influencing Emean in the pancreatic head and tail, respectively. The intra-operator stability of pancreatic 2-D SWE measurement was found to be excellent, whereas its inter-operator reproducibility was poor to good. CONCLUSION: Pancreatic 2-D SWE is a reliable technique for evaluating pancreatic stiffness in healthy adults, but its success rate and measurement value are influenced by multiple factors.

Development and Comparison of Prediction Models Based on Sonovue- and Sonazoid-Enhanced Ultrasound for Pathologic Grade and Microvascular Invasion in Hepatocellular Carcinoma.

OBJECTIVE: This study was aimed at developing and comparing prediction models based on Sonovue and Sonazoid contrast-enhanced ultrasound (CEUS) in predicting pathologic grade and microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Also investigated was whether Kupffer phase images have additional predictive value for the above pathologic features. METHODS: Ninety patients diagnosed with primary HCC who had undergone curative hepatectomy were prospectively enrolled. All patients underwent conventional ultrasound (CUS), Sonovue-CEUS and Sonazoid-CEUS examinations pre-operatively. Clinical, radiologic and pathologic features including pathologic grade, MVI and CD68 expression were collected. We developed prediction models comprising clinical, CUS and CEUS (Sonovue and Sonazoid, respectively) features for pathologic grade and MVI with both the logistic regression and machine learning (ML) methods. RESULTS: Forty-one patients (45.6%) had poorly differentiated HCC (p-HCC) and 37 (41.1%) were MVI positive. For pathologic grade, the logistic model based on Sonazoid-CEUS had significantly better performance than that based on Sonovue-CEUS (area under the curve [AUC], 0.929 vs. 0.848, p = 0.035), whereas for MVI, these two models had similar accuracy (AUC, 0.810 vs. 0.786, p = 0.068). Meanwhile, we found that well-differentiated HCC tended to have a higher enhancement ratio in 6-12 min during the Kupffer phase of Sonazoid-CEUS, as well as higher CD68 expression compared with p-HCC. In addition, all of these models can effectively predict the risk of recurrence (p < 0.05). CONCLUSION: Sonovue-CEUS and Sonazoid-CEUS were comparably excellent in predicting MVI, while Sonazoid-CEUS was superior to Sonovue-CEUS in predicting pathologic grade because of the Kupffer phase. The enhancement ratio in the Kupffer phase has additional predictive value for pathologic grade prediction.

Complementary Role of CEUS and CT/MR LI-RADS for Diagnosis of Recurrent HCC.

PURPOSE: We retrospectively compared the diagnostic performance of contrast-enhanced ultrasonography (CEUS) and contrast-enhanced computer tomography-magnetic resonance imaging (CT/MRI) for recurrent hepatocellular carcinoma (HCC) after curative treatment. MATERIALS AND METHODS: After curative treatment with 421 ultrasound (US) detected lesions, 303 HCC patients underwent both CEUS and CT/MRI. Each lesion was assigned a Liver Imaging Reporting and Data System (LI-RADS) category according to CEUS and CT/MRI LI-RADS. Receiver-operating characteristic (ROC) curves were computed to determine the optimal diagnosis algorithms for CEUS, CT and MRI. The diagnostic accuracy, sensitivity, specificity, and area under the curve (AUC) were compared between CEUS and CT/MRI. RESULTS: Among the 421 lesions, 218 were diagnosed as recurrent HCC, whereas 203 lesions were diagnosed as benign. In recurrent HCC, CEUS detected more arterial hyperenhancement (APHE) and washout than CT and more APHE than MRI. CEUS yielded better diagnostic performance than CT (AUC: 0.981 vs. 0.958) (p = 0.024) comparable diagnostic performance to MRI (AUC: 0.952 vs. 0.933) (p > 0.05) when using their optimal diagnostic criteria. CEUS missed 12 recurrent HCCs, CT missed one, and MRI missed none. The detection rate of recurrent HCC on CEUS (94.8%, 218/230) was lower than that on CT/MRI (99.6%, 259/260) (p = 0.001). Lesions located on the US blind spots and visualization score C would hinder the ability of CEUS to detect recurrent HCC. CONCLUSION: CEUS demonstrated excellent diagnostic performance but an inferior detection rate for recurrent HCC. CEUS and CT/MRI played a complementary role in the detection and characterization of recurrent HCC.

An Interpretable Radiomics Model Based on Two-Dimensional Shear Wave Elastography for Predicting Symptomatic Post-Hepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to develop and validate an interpretable radiomics model based on two-dimensional shear wave elastography (2D-SWE) for symptomatic post-hepatectomy liver failure (PHLF) prediction in patients undergoing liver resection for hepatocellular carcinoma (HCC). METHODS: A total of 345 consecutive patients were enrolled. A five-fold cross-validation was performed during training, and the models were evaluated in the independent test cohort. A multi-patch radiomics model was established based on the 2D-SWE images for predicting symptomatic PHLF. Clinical features were incorporated into the models to train the clinical-radiomics model. The radiomics model and the clinical-radiomics model were compared with the clinical model comprising clinical variables and other clinical predictive indices, including the model for end-stage liver disease (MELD) score and albumin-bilirubin (ALBI) score. Shapley Additive exPlanations (SHAP) was used for post hoc interpretability of the radiomics model. RESULTS: The clinical-radiomics model achieved an AUC of 0.867 (95% CI 0.787-0.947) in the five-fold cross-validation, and this score was higher than that of the clinical model (AUC: 0.809; 95% CI: 0.715-0.902) and the radiomics model (AUC: 0.746; 95% CI: 0.681-0.811). The clinical-radiomics model showed an AUC of 0.822 in the test cohort, higher than that of the clinical model (AUC: 0.684, p = 0.007), radiomics model (AUC: 0.784, p = 0.415), MELD score (AUC: 0.529, p < 0.001), and ALBI score (AUC: 0.644, p = 0.016). The SHAP analysis showed that the first-order radiomics features, including first-order maximum 64 × 64, first-order 90th percentile 64 × 64, and first-order 10th percentile 32 × 32, were the most important features for PHLF prediction. CONCLUSION: An interpretable clinical-radiomics model based on 2D-SWE and clinical variables can help in predicting symptomatic PHLF in HCC.

Stiffness on shear wave elastography as a potential microenvironment biomarker for predicting tumor recurrence in HBV-related hepatocellular carcinoma.

BACKGROUND: To explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection. METHODS: A total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS. RESULTS: Pathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction. CONCLUSIONS: Stiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC. CLINICAL RELEVANCE STATEMENT: Tumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment. KEY POINTS: • Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness. • Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma. • The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival. • The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77.

Predicting Infectious Complications after Percutaneous Thermal Ablation of Liver Malignancies: A 12-year Single-Center Experience.

Background Infectious complications after percutaneous thermal ablation are seldom discussed, but better understanding of risk factors and early prediction is critical. Purpose To estimate the incidence of infectious complications after percutaneous thermal ablation of liver malignancies and to develop prediction models. Materials and Methods This single-center retrospective study reviewed the data of 3167 patients who underwent 7545 percutaneous US-guided thermal ablation procedures of liver malignancies between January 2010 and January 2022. All procedures with infectious complications were included as the case group. For each case, one treatment date-matched control subject without infection was randomly selected following a nested case-control design. Independent factors of overall and hepatobiliary infection were investigated with multivariable logistic regression. Results A total of 80 patients (median age, 59 years; IQR, 51-68 years; 64 men, 16 women) developed infectious complications after 80 ablation procedures; the incidence was 1.1% (80 of 7545 procedures). Of those with infection, 18% (14 of 80 patients) were severe, and 10% (eight of 80 patients) died as a result. Independent risk factors for overall infectious complication included prior biliary intervention (odds ratio [OR], 18.6; 95% CI: 4, 86; P < .001), prior transarterial chemoembolization (TACE) (OR, 2.4; 95% CI: 1.0, 5.8; P = .045), and the largest tumor size (OR, 1.9; 95% CI: 1.3, 2.8; P = .002); on this basis, subcapsular location was an additional risk factor of hepatobiliary infection. Prediction models for overall and hepatobiliary infection had an area under the receiver operating characteristics curve (AUC) of 0.77 and 0.82, respectively, both of which showed better AUC compared with the models, including prior biliary intervention alone (AUC = 0.63 and 0.65, respectively; P = .01 and P = .005, respectively). Conclusion Infectious complications after percutaneous thermal ablation of liver malignancies were uncommon but potentially fatal. Independent predictors were prior biliary intervention, prior transarterial chemoembolization, and the largest tumor size. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ben-Arie and Sosna in this issue.

US LI-RADS in surveillance for recurrent hepatocellular carcinoma after curative treatment.

OBJECTIVES: To investigate the performance of US LI-RADS in surveillance for recurrent hepatocellular carcinoma (RHCC) after curative treatment. MATERIALS AND METHODS: This study enrolled 644 patients between January 2018 and August 2018 as a derivation cohort, and 397 patients from September 2018 to December 2018 as a validation cohort. The US surveillance after HCC curative treatment was performed. The US LI-RADS observation categories and visualization scores were analyzed. Four criteria using US LI-RADS or Alpha-fetoprotein (AFP) as the surveillance algorithm were evaluated. The sensitivity, specificity, and negative predictive value (NPV) were calculated. RESULTS: A total of 212 (32.9%) patients in derivation cohort and 158 (39.8%) patients in validation cohort were detected to have RHCCs. The criterion of US-2/3 or AFP ≥ 20 µg/L had higher sensitivity (derivation, 96.7% vs 92.9% vs 81.1% vs 90.6%; validation, 96.2% vs 90.5% vs 80.4% vs 89.9%) and NPV (derivation, 95.7% vs 93.3% vs 88.0% vs 91.8%; validation, 94.6% vs 89.4% vs 83.6% vs 89.0%), but lower specificity (derivation, 35.9% vs 48.2% vs 67.6% vs 51.9%; validation, 43.5% vs 52.7% vs 66.1% vs 54.0%) than criterion of US-2/3, US-3, and US-3 or AFP ≥ 20 µg/L. Analysis of the visualization score subgroups confirmed that the sensitivity (89.2-97.6% vs 81.0-83.3%) and NPV(88.4-98.0% vs 80.0-83.3%) of score A and score B groups were higher than score C group in criterion of US-2/3 in both two cohorts. CONCLUSIONS: In the surveillance for RHCC, US LI-RADS with AFP had a high sensitivity and NPV when US-2/3 or AFP ≥ 20 µg/L was considered a criterion. CLINICAL RELEVANCE STATEMENT: The criterion of US-2/3 or AFP ≥ 20 µg/L improves sensitivity and NPV for RHCC surveillance, which provides a valuable reference for patients in RHCC surveillance after curative treatment. KEY POINTS: • US LI-RADS with AFP had high sensitivity and NPV in surveillance for RHCC when considering US-2/3 or AFP ≥ 20 µg/L as a criterion. • After US with AFP surveillance, patients with US-2/3 or AFP ≥ 20 µg/L should perform enhanced imaging for confirmative diagnosis. Patients with US-1 or AFP < 20 µg/L continue to repeat US with AFP surveillance. • Patients with risk factors for poor visualization scores limited the sensitivity of US surveillance in RHCC.

Predicting symptomatic post-hepatectomy liver failure in patients with hepatocellular carcinoma: development and validation of a preoperative nomogram.

OBJECTIVE: To develop and validate a nomogram based on liver stiffness (LS) for predicting symptomatic post-hepatectomy (PHLF) in patients with hepatocellular carcinoma (HCC). METHODS: A total of 266 patients with HCC were enrolled prospectively from three tertiary referral hospitals from August 2018 to April 2021. All patients underwent preoperative laboratory examination to obtain parameters of liver function. Two-dimensional shear wave elastography (2D-SWE) was performed to measure LS. Three-dimensional virtual resection obtained the different volumes including future liver remnant (FLR). A nomogram was developed by using logistic regression and determined by receiver operating characteristic (ROC) curve analysis and calibration curve analysis, which was validated internally and externally. RESULTS: A nomogram was constructed with the following variables: FLR ratio (FLR of total liver volume), LS greater than 9.5 kPa, Child-Pugh grade, and the presence of clinically significant portal hypertension (CSPH). This nomogram enabled differentiation of symptomatic PHLF in the derivation cohort (area under curve [AUC], 0.915), internal fivefold cross-validation (mean AUC, 0.918), internal validation cohort (AUC, 0.876) and external validation cohort (AUC, 0.845). The nomogram also showed good calibration in the derivation, internal validation, and external validation cohorts (Hosmer-Lemeshow goodness-of-fit test, p = 0.641, p = 0.06, and p = 0.127, respectively). Accordingly, the safe limit of the FLR ratio was stratified using the nomogram. CONCLUSION: An elevated level of LS was associated with the occurrence of symptomatic PHLF in HCC. A preoperative nomogram integrating LS, clinical and volumetric features was useful in predicting postoperative outcomes in patients with HCC, which might help surgeons in the management of HCC resection. CLINICAL RELEVANCE STATEMENT: A serial of the safe limit of the future liver remnant was proposed by a preoperative nomogram for hepatocellular carcinoma, which might help surgeons in 'how much remnant is enough in liver resection'. KEY POINTS: • An elevated liver stiffness with the best cutoff value of 9.5 kPa was associated with the occurrence of symptomatic post-hepatectomy liver failure in hepatocellular carcinoma. • A nomogram based on both quality (Child-Pugh grade, liver stiffness, and portal hypertension) and quantity of future liver remnant was developed to predict symptomatic post-hepatectomy liver failure for HCC, which enabled good discrimination and calibration in both derivation and validation cohorts. • The safe limit of future liver remnant volume was stratified using the proposed nomogram, which might help surgeons in the management of HCC resection.

Predicting Post-hepatectomy Liver Failure Preoperatively for Child-Pugh A5 Hepatocellular Carcinoma Patients by Liver Stiffness.

BACKGROUND: Post-hepatectomy liver failure (PHLF) represents the major source of mortality after liver resection (LR) in hepatocellular carcinoma (HCC) patients. Child-Pugh (CP) score 5 is always considered to indicate a normal liver function but represents a heterogeneous population with a considerable number suffering from PHLF. The present study aimed to access the ability of liver stiffness (LS) measured by two-dimensional shear wave elastography (2D-SWE) to predict PHLF in HCC patients with a CP score of 5. METHODS: From August 2018 to May 2021, 146 HCC patients with a CP score of 5 who underwent LR were reviewed. The patients were randomly divided into training (n = 97) and validation (n = 49) groups. Logistic analyses were conducted for the risk factors and a linear model was built to predict the development of PHLF. The discrimination and calibration were assessed in the training and validation cohorts by the areas under the receiver operating characteristic curve (AUC). RESULTS: Analyses revealed that the minimum of LS (Emin) higher than 8.05 (p = 0.006, OR = 4.59) and future liver remnant / estimated total liver volume (FLR/eTLV) (p < 0.001, OR < 0.01) were independent predictors of PHLF in HCC patients with CP score 5, and the AUC calculated by the model based on them for differentiation of PHLF in the training and validation group was 0.78 and 0.76, respectively. CONCLUSION: LS was associated with the development of PHLF. A model combining Emin and FLR/eTLV showed proper ability in predicting PHLF in HCC patients with a CP score of 5.

Shear-wave elastography combined with contrast-enhanced ultrasound algorithm for noninvasive characterization of focal liver lesions.

PURPOSE: To establish shear-wave elastography (SWE) combined with contrast-enhanced ultrasound (CEUS) algorithm (SCCA) and improve the diagnostic performance in differentiating focal liver lesions (FLLs). MATERIAL AND METHODS: We retrospectively selected patients with FLLs between January 2018 and December 2019 at the First Affiliated Hospital of Sun Yat-sen University. Histopathology was used as a standard criterion except for hemangiomas and focal nodular hyperplasia. CEUS with SonoVue (Bracco Imaging) and SCCA combining CEUS and maximum value of elastography with < 20 kPa and > 90 kPa thresholds were used for the diagnosis of FLLs. The diagnostic performance of CEUS and SCCA was calculated and compared. RESULTS: A total of 171 FLLs were included, with 124 malignant FLLs and 47 benign FLLs. The area under curve (AUC), sensitivity, and specificity in detecting malignant FLLs were 0.83, 91.94%, and 74.47% for CEUS, respectively, and 0.89, 91.94%, and 85.11% for SCCA, respectively. The AUC of SCCA was significantly higher than that of CEUS (P = 0.019). Decision curves indicated that SCCA provided greater clinical benefits. The SCCA provided significantly improved prediction of clinical outcomes, with a net reclassification improvement index of 10.64% (P = 0.018) and integrated discrimination improvement of 0.106 (P = 0.019). For subgroup analysis, we divided the FLLs into a chronic-liver-disease group (n = 88 FLLs) and a normal-liver group (n = 83 FLLs) according to the liver background. In the chronic-liver-disease group, there were no differences between the CEUS-based and SCCA diagnoses. In the normal-liver group, the AUC of SCCA and CEUS in the characterization of FLLs were 0.89 and 0.83, respectively (P = 0.018). CONCLUSION: SCCA is a feasible tool for differentiating FLLs in patients with normal liver backgrounds. Further investigations are necessary to validate the universality of this algorithm.

Combinatory local ablation and immunotherapies for hepatocellular carcinoma: Rationale, efficacy, and perspective.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Local ablation, such as radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation, etc., are well established in elimination and control of HCC. However, high recurrence rate after local ablation remains the biggest challenge for HCC management. Novel and effective therapeutic strategies to improve long-term survival are urgently needed. Accumulating studies have reported the role of ablation in modulating the tumor signaling pathway and the immune microenvironment to both eliminate residual/metastatic tumor and promote tumor progression. Ablation has been shown to elicit tumor-specific immune responses by inducing massive cell death and releasing tumor antigen. Immunotherapies that unleash the immune system have the potential to enhance the anti-tumor immunity induced by ablation. Multiple combinatory strategies have been explored in preclinical and clinical studies. In this review, we comprehensively summarize the latest progress on different mechanisms underlying the effects of ablation on tumor cells and tumor microenvironment. We further analyze the clinical trials testing the combination of ablation and immunotherapies, and discuss the possible role of immunomodulation to boost the anti-tumor effects of ablation and prevent HCC recurrence.

Identification of the origin of tumor in vein: comparison between CEUS LI-RADS v2017 and v2016 for patients at high risk.

OBJECTIVES: To compare the diagnostic performance of the Contrast-Enhanced Ultrasound (CEUS) Liver Imaging Report and Data System (LI-RADS) v2016 and v2017 in identifying the origin of tumor in vein (TIV). METHODS: From April 2014 to December 2018, focal liver lesions (FLLs) accompanied by TIV formation in patients at high risk for hepatocellular carcinoma (HCC) were enrolled. Histologic evaluation or composite imaging reference standard were served as the reference standard. Each case was categorized according to the CEUS LI-RADS v2016 and v2017, respectively. Diagnostic performance of CEUS LI-RADS v2016 and v2017 in identifying the originated tumor of TIV was validated via sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value. RESULTS: A total of 273 FLLs with TIV were analyzed finally, including 266 HCCs and 7 non-HCCs. In v2016, when adopting all TIV as LR-5V, the accuracy and PPV in identifying the originated tumor were both 97.4%. In v2017, when assigning TIV according to contiguous FLLs CEUS LI-RADS category, the accuracy and PPV were 61.9% and 99.4% in subclass of LR-5 as the diagnostic criteria of HCC, and 64.1% and 99.4% in subclass of LR-4/5 as the criteria of HCC diagnosis. There were significant differences in diagnostic accuracy between CEUS LI-RADS v2016 and v2017 in identifying the originated tumor of TIV (p < 0.001). CONCLUSIONS: CEUS LI-RADS v2016 could be better than v2017 in identifying the originated tumor of TIV.

The "stiff rim" sign of hepatocellular carcinoma on shear wave elastography: correlation with pathological features and potential prognostic value.

PURPOSE: To explore the pathologic basis, the influencing factors and potential prognostic value of the stiff rim sign in two-dimensional shear wave elastography (2D-SWE) of hepatocellular carcinoma (HCC). METHODS: HCC patients who underwent tumor 2D-SWE examination before resection were prospectively enrolled. The stiff rim sign was defined as increased stiffness in the peritumoral region. Interobserver and intraobserver variability of the stiff rim sign was assessed. The correlation between the stiff rim sign and pathological characteristics was analyzed. Multivariate analysis was performed to examine clinical and radiological factors influencing the appearance of stiff rim sign. The Kaplan-Meier method was used to analyze the relationship between recurrence-free survival (RFS) and the stiff rim sign. RESULTS: The stiff rim sign on 2D-SWE was present in 44.7% of HCC lesions. Interobserver agreement and intraobserver agreement for the stiff rim sign were substantial (κ = 0.772) and almost perfect (κ = 0.895), respectively. Pathologically, the stiff rim sign was associated with capsule status, capsule integrity, capsule thickness, proportion of peritumoral fibrous tissue, and peritumoral fibrous arrangement. Multivariate analysis showed that tumor size was an independent clinical predictor for the appearance of stiff rim sign (OR 1.201, p = 0.008). Kaplan-Meier analysis showed RFS was significantly poorer in the stiff rim sign (+) group than the stiff rim sign (-) group in solitary tumors smaller than 5 cm (p = 0.007) and solitary tumors with intratumoral stiffness less than 33.7 kPa (p = 0.007). CONCLUSION: The stiff rim sign on 2D-SWE was mainly correlated with peritumoral fibrous tissue status and was a poor prognostic indicator for HCC.

Preoperative prognostic value of alfa-fetoprotein density in patients with hepatocellular carcinoma undergoing radiofrequency ablation.

OBJECTIVES: To examine the prognostic value of preoperative alfa-fetoprotein (AFP) density and other clinical factors in patients undergoing percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS: From January 2010 to December 2018, a total of 543 patients undergoing RFA for HCC meeting the Milan criteria were included at our institution. AFP density was calculated as absolute AFP pre-ablation divided by the total volume of all HCC lesions. The survival rates according to AFP density were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazards regression analyses were used to assess predictors of overall survival (OS) and progression-free survival (PFS). RESULTS: The Kaplan-Meier 1-, 3-, and 5-year OS rates were 98.8%, 88.5%, and 70.4%, respectively, for the low AFP density group, and 98.3%, 74.9%, and 49.4%, respectively, for the high AFP density group. The corresponding PFS rates were 78.9%, 56.7%, and 40.9% (low AFP density group), and 63.6%, 40.8%, and 27.5% (high AFP density group). High AFP density was associated with significantly reduced PFS and OS (both p < 0.001). Multivariate analysis suggested that AFP density was a predictor of OS and PFS. CONCLUSIONS: Serum AFP density may serve as a promising predictor of survival in patients with HCC undergoing RFA. High AFP density could identify patients who might be prone to recurrence or progression and need close surveillance.

Application of the CT/MRI LI-RADS Treatment Response Algorithm to Contrast-Enhanced Ultrasound: A Feasibility Study.

Purpose: The contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (TRA) is still in development. The aim of this study was to explore whether the CT/MRI LI-RADS TRA features were applicable to CEUS in evaluating the liver locoregional therapy (LRT) response. Patients and Methods: This study was a retrospective review of a prospectively maintained database of patients with hepatocellular carcinoma undergoing ablation between July 2017 and December 2018. The standard criteria for a viable lesion were a histopathologically confirmed or typical viable appearance in the follow-up CT/MRI. Performance of the LI-RADS TRA assessing tumor viability was then compared between CEUS and CT/MRI. Inter-reader association was calculated. Results: A total of 244 patients with 389 treated observations (118 viable) were evaluated. The sensitivity and specificity of the CEUS TRA and CT/MRI LI-RADS TRA viable categories for predicting viable lesions were 55.0% (65/118) versus 56.8% (67/118) (P = 0.480) and 99.3% (269/271) versus 96.3% (261/271) (P = 0.013), respectively. The PPV of CEUS was higher than that of CT/MRI (97.0% vs 87.0%). Subgroup analysis showed that the sensitivity was low in the 1-month assessment for both CEUS (38.1%, 16/42) and CT/MR (47.6%, 20/42) and higher in the 2-6-month assessment for both CEUS (65.7%, 23/35) and CT/MR (62.9%, 22/35). Interobserver agreements were substantial for both CEUS TRA and CT/MRI LI-RADS TRA (κ, 0.74 for both). Conclusion: The CT/MRI LI-RADS TRA features were applicable to CEUS TRA for liver locoregional therapy. The CEUS TRA for liver locoregional therapy has sufficiently high specificity and PPV to diagnose the viability of lesions after ablation.

High-Frequency US for BK Polyomavirus-associated Nephropathy after Kidney Transplant.

Background BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of chronic renal allograft dysfunction. However, US features indicative of BKPyVAN have not been fully evaluated. Purpose To assess the value of high-frequency US for the diagnosis of BKPyVAN in kidney transplant recipients. Materials and Methods In this prospective cohort study, participants who tested positive for BK viruria after kidney transplant from September 2019 to January 2021 were evaluated with high-frequency US 1 day before biopsy. Clinical characteristics and US features were compared between participants with and without BKPyVAN. Significant predictors associated with BKPyVAN were determined using logistic regression analyses. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic performance. Results A total of 105 participants who underwent kidney transplant (mean age, 38 years ± 11 [SD]; 63 men) were evaluated; 45 participants were diagnosed with BKPyVAN. Multivariable analysis demonstrated that eccentric hydronephrosis and subcapsular hypoechoic areas were independent factors for BKPyVAN. The AUC for predicting BKPyVAN according to subcapsular hypoechoic areas was 0.66 (95% CI: 0.55, 0.77), with a specificity of 92% (55 of 60 participants). The AUC of combined US (eccentric hydronephrosis plus subcapsular hypoechoic area) and clinical (urine BKPyV DNA load [BKPyV-DNA] plus BK viremia) features was 0.90, with a specificity of 92% (55 of 60 participants). Parenchymal hyperechoic and subcapsular hypoechoic areas were independent factors for differentiating BKPyVAN from transplant rejection. The pooled specificity of subcapsular hypoechoic areas was 96% (21 of 22 participants), with an AUC of 0.67 (95% CI: 0.54, 0.80). For the combination of US (parenchymal echogenicity plus subcapsular hypoechoic area) and clinical (urine BKPyV-DNA plus time since transplant) features, the AUC reached 0.92 and specificity was 82% (18 of 22 participants). Conclusion High-frequency US characteristics are valuable for diagnosing BK polyomavirus-associated nephropathy (BKPyVAN) and distinguishing BKPyVAN from rejection in kidney transplant recipients. © RSNA, 2022 Online supplemental material is available for this article.

Radiomics models for preoperative prediction of microvascular invasion in hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: To assess the methodological quality and to evaluate the predictive performance of radiomics studies for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: Publications between 2017 and 2021 on radiomic MVI prediction in HCC based on CT, MR, ultrasound, and PET/CT were included. The risk of bias was assessed using the prediction model risk of bias assessment tool (PROBAST). Methodological quality was assessed through the radiomics quality score (RQS). Fourteen studies classified as TRIPOD Type 2a or above were used for meta-analysis using random-effects model. Further analyses were performed to investigate the technical factors influencing the predictive performance of radiomics models. RESULTS: Twenty-three studies including 4947 patients were included. The risk of bias was mainly related to analysis domain. The RQS reached an average of (37.7 ± 11.4)% with main methodological insufficiencies of scientific study design, external validation, and open science. The pooled areas under the receiver operating curve (AUC) were 0.85 (95% CI 0.82-0.89), 0.87 (95% CI 0.83-0.92), and 0.74 (95% CI 0.67-0.80), respectively, for CT, MR, and ultrasound radiomics models. The pooled AUC of ultrasound radiomics model was significantly lower than that of CT (p = 0.002) and MR (p < 0.001). Portal venous phase for CT and hepatobiliary phase for MR were superior to other imaging sequences for radiomic MVI prediction. Segmentation of both tumor and peritumor regions showed better performance than tumor region. CONCLUSION: Radiomics models show promising prediction performance for predicting MVI in HCC. However, improvements in standardization of methodology are required for feasibility confirmation and clinical translation.