Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. METHODS: Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. RESULTS: There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P = .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P = .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P = .038). CONCLUSIONS: A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Hepatocellular Carcinoma ≤5 cm: Biological Characteristics and Patient Outcomes.

Introduction: The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection. Methods: Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm, as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67, and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI-RADS categories were further analyzed. Results: A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (p < 0.001) and levels of Ki-67 (p = 0.01) and that poor differentiation (32.7% in LR-M, 12% in LR-5, and 6.2% in LR-4) (p < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5, and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (p > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection. Conclusions: Biological characteristics of HCC, including differentiation and level of Ki-67 expression, could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.

Period-Dependent Survival Benefit of Percutaneous Microwave Ablation for Hepatocellular Carcinoma: A 12-Year Real-World, Multicentric Experience.

Introduction: Although microwave ablation (MWA) is a promising technique for hepatocellular carcinoma (HCC) treatment, its 10-year efficacy is unknown. Objective: The objective of the study was to assess whether the advances in MWA for HCC translated into a real-world survival benefit. Methods: This retrospective study included 2,354 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 to B from 5 hospitals, with at least 2 years of follow-up for all the patients. Recurrence and survival were analyzed using the Kaplan-Meier method with time-period stratification. Results: A total of 5,326 HCCs (mean diameter, 2.9 cm ± 1.2) underwent 4,051 sessions of MWA with a median follow-up of 61.3 (0.6-169.5 range) months during 3 periods (2007-2010, 2011-2014, and 2015-2018). Technical success was achieved in 5,194 (97.5%) tumors with significant improvement over time, especially for >3.0-cm HCC (p < 0.001). Local tumor progression (LTP) showed no period-dependent advance, with >3.0-cm HCC and perivascular location being the risk factors for LTP. The median intrahepatic metastasis time was 27.6 (95% confidence interval [CI]: 25.2-28.8) months, with 5- and 10-year occurrence rates of 68.8% and 79.4%, respectively. The 5- and 10-year overall survivals were 63.9% and 41.1%, respectively, and BCLC stage 0, A, and all B patients showed an observable survival improvement over time (p < 0.001). The median disease-free survival time increased from 19.4 (95% CI: 16.5-22.6) months in 2007-2010 to 28.1 (95% CI: 25.9-32.3) months in 2015-2018. The improved survival for early recurrent (≤2 years) patients was period-dependent, as verified by Cox regression analyses. The major complications rate per procedure was 3.0% (122/4,051). Conclusions: These real-world data show that MWA provided an upward trend in survival for HCC patients with BCLC stage 0-B over a 12-year follow-up period. An encouraging clear survival benefit in early recurrent patients was also observed.

US Shear-Wave Elastography Dispersion for Characterization of Chronic Liver Disease.

Background Little is known about the benefits of the use of dispersion slope (DS) as a viscosity-related parameter derived from two-dimensional (2D) shear-wave elastography (SWE) in the stratification of hepatic pathologic stages. Purpose To evaluate whether DS as an additional parameter can improve the diagnostic performance in detecting liver necroinflammation, fibrosis, and steatosis. Materials and Methods In this prospective study, consecutive participants with chronic liver disease who underwent liver biopsy and 2D SWE were recruited between July 2019 and September 2020. DS and liver stiffness (LS) measurements were obtained with use of a 2D SWE system immediately before biopsy. The biopsy specimens were assessed to obtain the scores of fibrosis, necroinflammation, and steatosis. Differences in the area under the receiver operating characteristic curve (AUC) were used to compare the diagnostic performance of DS, LS, and a combination of DS and LS. Results There were 159 participants evaluated (among them, 79 participants with chronic hepatitis B and 11 participants with nonalcoholic fatty liver disease). The distributions of DS values among various necroinflammatory activities (P = .02) and fibrosis stages (P < .001) were different. Moreover, DS was only associated with fibrosis after subgroup analysis based on the fibrosis stages and necroinflammatory activities (P < .001). The AUCs of DS in detecting clinically significant fibrosis (fibrosis stage ≥F2), cirrhosis (fibrosis stage of F4), and moderate to severe necroinflammatory activity (necroinflammatory activity ≥A2) were 0.72 (95% CI: 0.64, 0.79), 0.71 (95% CI: 0.63, 0.78), and 0.64 (95% CI: 0.55, 0.71), respectively. The differences of AUCs were not apparent for the DS and LS combination model after excluding DS (fibrosis stage ≥F2: 0.00 [95% CI: 0.00, 0.01], fibrosis stage of F4: -0.01 [95% CI: -0.02, 0.00], and necroinflammatory activity ≥A2: 0.00 [95% CI: 0.00, 0.01]). Conclusion The addition of dispersion slope derived from two-dimensional shear-wave elastography did not improve the diagnostic performance in detecting liver fibrosis, necroinflammation, or steatosis in patients with primarily viral hepatitis. ClinicalTrials.gov registration no.: NCT03777293 © RSNA, 2022 Online supplemental material is available for this article.

Usefulness of New Shear Wave Elastography Technique for Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B: A Prospective Multicenter Study.

PURPOSE: To explore the usefulness of liver stiffness measurements (LSMs) by sound touch elastography (STE) and sound touch quantification (STQ) in chronic hepatitis B (CHB) patients for staging fibrosis. METHODS: This prospective multicenter study recruited normal volunteers and CHB patients between May 2018 and October 2019. The volunteers underwent LSM by STE and supersonic shear imaging (SSI) or by STQ and acoustic radiation force impulse imaging (ARFI). CHB patients underwent liver biopsy and LSM by both STE/STQ. The areas under the receiver operating characteristic curves (AUCs) for staging fibrosis were calculated. RESULTS: Overall, 97 volunteers and 524 CHB patients were finally eligible for the study. The successful STE and STQ measurement rates were both 100 % in volunteers and 99.4 % in CHB patients. The intraclass correlation coefficients (ICCs) for the intra-observer stability of STE and STQ (0.94; 0.90) were similar to those of SSI and ARFI (0.95; 0.87), respectively. STE and STQ showed better accuracy than the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) (AUC: 0.87 vs 0.86 vs 0.73 vs 0.77) in staging cirrhosis. However, both STE and STQ were not superior to APRI and FIB-4 in staging significant fibrosis (AUC: 0.76 vs 0.73 vs 0.70 vs 0.71, all P-values > 0.05). CONCLUSION: STE and STQ are convenient techniques with a reliable LSM value. They have a similar diagnostic performance and are superior to serum biomarkers in staging cirrhosis in CHB patients.

Shear-Wave Dispersion Slope of the Liver: Effect of Study Protocol and Ascites on the Measurement Applicability.

This study aimed to evaluate the shear-wave dispersion (SWD) scanning protocol including the minimum number of measurements and better size of the region of interest (ROI), as well as the influence of ascites on the measurement applicability. Patients who had undergone serial SWD examinations between July 2019 and December 2020 were included. In patients with chronic liver disease (group A), two different ROI sizes were applied, and at least 10 measurements were repeated to determine the minimum number of measurements and better ROI size. In patients with liver failure (group B), failure and unreliable results were compared between patients with and without ascites. A minimum of five measurements when using a 20-mm ROI and six measurements when using a 10-mm ROI were required. Compared with using a 20-mm ROI, a 10-mm ROI showed a higher unreliable rate. The failure and unreliable rates of SWD in patients with ascites were significantly higher than those in patients without ascites. SWD examination required at least five measurements when using a 20-mm ROI and six measurements when using a 10-mm ROI. A larger ROI was associated with higher reliability, and ascites influenced the failure and reliability of the SWD measurement.

An Optimal Ablative Margin of Small Single Hepatocellular Carcinoma Treated with Image-Guided Percutaneous Thermal Ablation and Local Recurrence Prediction Base on the Ablative Margin: A Multicenter Study.

OBJECTIVE: To explore the best ablative margin (AM) for single hepatocellular carcinoma (HCC) patients with image-guided percutaneous thermal ablation (IPTA) based on MRI-MRI fusion imaging, and to develop and validate a local tumor progression (LTP) predictive model based on the recommended AM. METHODS: Between March 2014 and August 2019, 444 treatment-naïve patients with single HCC (diameter ≤3 cm) who underwent IPTA as first-line treatment from three hospitals were included, which were randomly divided into training (n= 296) and validation (n = 148) cohorts. We measured the ablative margin (AM) by MRI-MRI fusion imaging based on pre-ablation and post-ablation images. Then, we followed up their LPT and verified the optimal AM. Risk factors related to LTP were explored through Cox regression models, the nomogram was developed to predict the LTP risk base on the risk factors, and subsequently validated. The predictive performance and discrimination were assessed and compared with conventional indices. RESULTS: The median follow-up was 19.9 months (95% CI 18.0-21.8) for the entire cohort. The results revealed that the tumor size (HR: 2.16; 95% CI 1.25-3.72; P = 0.003) and AM (HR: 0.72; 95% CI, 0.61-0.85; P < 0.001) were independent prognostic factors for LTP. The AM had a pronounced nonlinear impact on LTP, and a cut-off value of 5-mm was optimal. We developed and validated an LTP predictive model based on the linear tumor size and nonlinear AM. The model showed good predictive accuracy and discrimination (training set, concordance index [C-index] of 0.751; validation set, C-index of 0.756) and outperformed other conventional indices. CONCLUSION: The 5-mm AM is recommended for the best IPTA candidates with single HCC (diameter ≤3 cm). We provided an LTP predictive model that exhibited adequate performance for individualized prediction and risk stratification.

CEUS detection of biliary ischaemia during the first 4 weeks after liver transplantation predicts non-anastomotic biliary stricture.

BACKGROUND: Biliary ischaemia is an important factor in the pathogenesis of non-anastomotic biliary stricture (NAS) after liver transplantation (LT). Contrast-enhanced ultrasound (CEUS) can be used to detect biliary ischaemia, but no study has examined the utility of CEUS in predicting NAS. OBJECTIVE: To evaluate whether repeated CEUS as a non-invasive method of biliary ischaemia can identify NAS. METHODS: Consecutive LT patients who underwent CEUS examinations at 1-4 weeks after LT from September 2012 to December 2015 at our institution were included. The CEUS images and clinical data were analysed. RESULTS: Among 116 eligible LT patients, 39 (33.6%) were diagnosed with NAS within 1 year after LT. The patients with NAS had a significantly higher CEUS score at weeks 2-4 (all P < 0.05) and a higher slope of CEUS score progression (0.480 vs -0.044, P < 0.001). The accuracy of CEUS in identifying NAS improved over time after LT, reaching its maximum at week 4, with a sensitivity of 66.7%, a specificity of 87.9%, a positive predictive value (PPV) of 75.9%, a negative predictive value (NPV) of 82.3%, and an accuracy of 80.2%in the full cohort when a CEUS score≥3 was used as the cut-off. Multivariate analysis identified gamma-glutamyl transpeptidase (GGT), alanine transaminase (ALT) and the CEUS score at week 4 as independent predictors of NAS. In the task of identifying NAS, an NAS score combining the above 3 variables at week 4 showed areas under the receiver operating characteristic curve of 0.88 (95%CI, 0.78-0.99) in the estimation group (n = 60) and 0.82 (95%CI, 0.69-0.96) in the validation group (n = 56). An NAS score cut-off of 0.396 identified 87.2%of NAS cases in the estimation group, with a PPV of 93.3%; and 75.0%of NAS cases in the validation group, with a PPV of 58.8%. CONCLUSIONS: CEUS examination during the first 4 weeks is useful in assessing the risk of NAS within 1 year after LT. In particular, an NAS score combining the CEUS score, GGT level, and ALT level at week 4 can be used to accurately predict the risk of NAS in LT patients.

Role of ultrasound in the diagnosis of primary and recurrent dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare, low- to intermediate-grade sarcoma, which represents a diagnostic imaging challenge. This study aimed to analyze the clinical and ultrasound features of primary and recurrent DFSP to improve the diagnosis. METHODS: Clinical, imaging, and pathological data from a total of 58 patients (23 patients with primary DFSP and 35 patients with recurrent DFSP) were retrospectively reviewed. RESULTS: There was no statistically significant difference in age, sex, tumor size, or echogenicity between the two groups. Most of the primary DFSP lesions involved the overlying dermis and hypodermis, while most of the recurrent DFSP lesions were fixated to more deeply seated structures at the original surgical incision. Red nodules on the skin were found more frequently in the primary group. There were statistically significant differences in the type of lesion and ultrasound tumor morphology (p < 0.050). The lesions in the primary group showed more tentacle-like projections or a "claw" sign, while the lesions in the recurrent group were more commonly oval, lobulated, and irregularly shaped. Hypervascularity was common in both groups. CONCLUSIONS: For primary DFSP, a slow-growing, red nodule on the skin involving the overlying dermis and hypodermis, more frequently a hypoechoic mass with tentacle-like projections or a "claw" sign, was observed. For recurrent DFSP, palpable subcutaneous nodules or subcutaneous masses at the original surgical incision and oval, lobulated, and irregularly shaped lesions were more commonly observed. This may be useful for improving diagnostic accuracy.

Dynamic Contrast-Enhanced Ultrasound Radiomics for Hepatocellular Carcinoma Recurrence Prediction After Thermal Ablation.

PURPOSE: To develop a radiomics model based on dynamic contrast-enhanced ultrasound (CEUS) to predict early and late recurrence in patients with a single HCC lesion ≤ 5 cm in diameter after thermal ablation. PROCEDURES: We enrolled patients who underwent thermal ablation for HCC in our hospital from April 2004 to April 2017. Radiomics based on two branch convolution recurrent network was utilized to analyze preoperative dynamic CEUS image of HCC lesions to establish CEUS model, in comparison to the conventional ultrasound (US), clinical, and combined models. Clinical follow-up of HCC recurrence after ablation were taken as reference standard to evaluate the predicted performance of CEUS model and other models. RESULTS: We finally analyzed 318 patients (training cohort: test cohort = 255:63). The combined model showed better performance for early recurrence than CUES (in training cohort, AUC, 0.89 vs. 0.84, P < 0.001; in test cohort, AUC, 0.84 vs. 0.83, P = 0.272), US (P < 0.001), or clinical model (P < 0.001). For late recurrence prediction, the combined model showed the best performance than the CEUS (C-index, in training cohort, 0.77 vs. 0.76, P = 0.009; in test cohort, 0.77 vs. 0.68, P < 0.001), US (P < 0.001), or clinical model (P < 0.001). CONCLUSIONS: The CEUS model based on dynamic CEUS radiomics performed well in predicting early HCC recurrence after ablation. The combined model combining CEUS, US radiomics, and clinical factors could stratify the high risk of late recurrence.

Clinical and Contrast-enhanced Ultrasound Characteristics of Epithelioid and Classic Hepatic Angiomyolipoma: Comparison With Alpha-fetoprotein-negative Hepatocellular Carcinoma.

Hepatic angiomyolipoma (HAML) comprises epithelioid angiomyolipoma (EAML) and classic hepatic angiomyolipoma (CAML). The imaging appearance of HAML varies widely, and EAML is more easily misdiagnosed as hepatocellular carcinoma (HCC) than as CAML. The clinical and contrast-enhanced ultrasound (CEUS) features of CAML, EAML and HCC with negative alpha-fetoprotein protein expression (HCC[AFP-]) were retrospectively reviewed. The hyper-vascular type was more commonly found in CAML and EAML lesions than in HCC lesions. Most lesions were hyper-enhanced in the arterial phase. CAMLs showed prolonged hyper-enhancement or iso-enhancement during the portal and late phases on CEUS, making them easily distinguishable from HCC(AFP-). Some EAML lesions (41.7%) were hypo-echoic, similar to HCC(AFP-). However, the hypo-enhancement of EAML lesions occurred later than that of HCC(AFP-) lesions. Thus, our findings may be useful in distinguishing among these lesions to improve diagnostic accuracy.

Contrast-Enhanced Ultrasound for Biliary Ischemia: A Possible New Clinical Indication.

OBJECTIVES: Biliary perfusion is considered to contribute to biliary diseases, but routine imaging methods are insufficient to show it. This research investigated the ability of contrast-enhanced ultrasound (CEUS) for biliary perfusion in a biliary ischemia model. METHODS: This research consisted of 2 parts. First, to determine whether CEUS enhancement of the tiny biliary wall represents biliary perfusion, a vascular tracer was used as a reference to evaluate the consistency with the enhancement of the biliary wall on CEUS and the staining by the vascular tracer under the conditions of occluded and recovered biliary perfusion. In the second part, the ability of CEUS for biliary ischemia was further evaluated with microvascular density measurement as a reference. The enhancement patterns were assigned CEUS scores, in which higher scores meant more decreased enhancement, and the diagnostic ability of CEUS was assessed by a receiver operating characteristic curve analysis. RESULTS: The biliary wall was unstained by the vascular tracer and nonenhanced on CEUS when biliary perfusion was interrupted and was stained blue and enhanced after recovery. The biliary wall in the ischemia surgery group showed lower microvascular density measurements (P < .001), decreased enhancement levels (P < .001), and higher CEUS scores (P < .001). When a CEUS score of 3 or higher (obvious decrease of the biliary wall to hypoenhancement or nonenhancement in the arterial phase or rapid wash-out to nonenhancement in the portal venous phase) was applied, CEUS had sensitivity of 87.8%, specificity of 98.3%, accuracy of 93.8%, and an area under the receiver operating characteristic curve of 0.98. CONCLUSIONS: Contrast enhancement of the biliary wall on CEUS represents biliary perfusion and has reasonably good diagnostic performance for biliary ischemia in an experimental animal setting.

Intraprocedural contrast-enhanced ultrasound-CT/MR fusion imaging assessment in HCC thermal ablation to reduce local tumor progression: compared with routine contrast-enhanced ultrasound.

Purpose: To evaluate whether local tumor progression (LTP) would be further reduced when contrast-enhanced ultrasound (CEUS)-CT/MR fusion imaging was used as intraprocedural assessment method in hepatocellular carcinoma (HCC) thermal ablation compared with routine CEUS. Materials and methods: This prospective non-randomized study was conducted from December 2010 to July 2012. CEUS-CT/MR fusion imaging and routine CEUS were used for treatment response assessment in the ablation procedure of 146 HCCs and 122 HCCs, respectively. Supplementary ablations were performed immediately if necessary. The primary technique efficacy rate, LTP rate and overall survival (OS) rate were calculated. Results: For CEUS-CT/MR fusion imaging and routine CEUS, the technical success rate, technique efficacy rate and supplementary ablation rate were 86.3% (126/146) and 98.4% (120/122) (p = .000), 99.2% (125/126) and 94.2% (113/120) (p = .032), and 14.3% (18/126) and 4.2% (5/120) (p = .006), respectively. The cumulative LTP rate and OS rate were not significantly different between fusion imaging group and routine CEUS group. However, for lesions that were larger than 3 cm or close to major vessels (41 lesions in fusion imaging group and 44 lesions in routine CEUS group, who received transcatheter arterial chemoembolization before ablation), the cumulative LTP rate was significantly lower in fusion imaging group than in routine CEUS group (p = .032). Conclusion: Although intraprocedural CEUS-CT/MR fusion imaging has certain limitations in application, it might provide a potential more efficient method compared with routine CEUS in reducing LTP in HCC thermal ablation, especially for difficult ablation lesions.

Paclitaxel-loaded nanobubble targeted to pro-gastrin-releasing peptide inhibits the growth of small cell lung cancer.

OBJECTIVE: The aim of this work was to study the effects of paclitaxel-loaded nanobubbles targeting pro-gastrin-releasing peptide, designated as paclitaxel targeting nanobubbles, on small cell lung cancer (SCLC). METHODS: Paclitaxel targeting nanobubbles were prepared by Thin-film hydration method. Subsequently, the prepared nanomaterials were tested for their in vitro effects on SCLC H446 cells proliferation, apoptosis and motility using the CCK-8 assay, flow cytometry and cell scratch test. Next, the potential molecular regulatory mechanisms of the prepared nanomaterials on H446 cells were evaluated by RT-PCR, Western blot and immunohistochemical detection. Finally, the in vivo effects of the constructed nanomaterials were assessed on SCLC tumor using tumor-burdened nude mice models. RESULTS: Paclitaxel targeting nanobubbles significantly inhibited SCLC cell proliferation and migration, and promoted cell apoptosis. Moreover, the expression levels of Bcl-2, survivin, CDK2 and MMP-2 significantly decreased in SCLC cells treated with paclitaxel targeting nanobubbles, whereas the expression of caspase-3 and Rb were increased. There was a notable decrease in tumor size in vivo in SCLC nude mice models treated with paclitaxel targeting nanobubbles. CONCLUSION: Paclitaxel targeting nanobubbles effectively inhibited the proliferation, migration and invasion of SCLC cells and induced SCLC cells apoptosis. Hence, these nanobubbles show potential in SCLC-targeted drug treatment application.

Intraprocedural computed tomography/magnetic resonance-contrast-enhanced ultrasound fusion imaging improved thermal ablation effect of hepatocellular carcinoma: Comparison with conventional ultrasound.

AIM: To retrospectively compare the treatment effect of intraprocedural computed tomography/magnetic resonance-contrast-enhanced ultrasound (CT/MR-CEUS) fusion imaging (FI) with that of conventional ultrasound (US) in the guidance and assessment of thermal ablation of hepatocellular carcinoma (HCC). METHODS: The FI group (112 patients with 129 HCC) was treated between April 2010 and December 2012, whereas the US group (83 patients with 90 HCC) was treated between January 2008 and March 2010. Either CT/MR-CEUS FI or US was used to guide puncture, provide immediate assessment, and guide supplementary ablation. Technical efficacy, cumulative local tumor progression rate (LTP), recurrence-free survival (RFS), and overall survival (OS) were evaluated and compared during follow-up. Technical success rate of CT/MR-CEUS FI was also recorded. RESULTS: Technical efficacy was significantly higher in the FI group than in the US group (100% vs. 86.7%, P < 0.001). The 1-, 2-, 3-, 4-, 5-, and 6-year cumulative LTP rates in the FI group were significantly lower than in the US group (3.8%, 4.9%, 6.0%, 6.0%, 7.2%, and 7.2% vs. 16.9%, 20.1%, 25%, 25%, 25%, and 25%, respectively; P < 0.001); RFS and OS were significantly higher in the FI group than in the US group (P = 0.027 and P = 0.049, respectively). The technical success rate of FI was 85.3%. CONCLUSIONS: Intraprocedural CT/MR-CEUS FI improved the treatment effect of thermal ablation of HCC by immediately assessing treatment response and guiding supplementary ablation relative to those resulting from the use of conventional US.

Shear wave elastography for liver fibrosis in chronic hepatitis B: Adapting the cut-offs to alanine aminotransferase levels improves accuracy.

OBJECTIVES: To determine and validate alanine aminotransferase (ALT)-adapted dual cut-offs of liver stiffness measurements (LSMs) for assessing liver fibrosis with two-dimensional shear wave elastography (2D-SWE) in patients with chronic hepatitis B (CHB) infection. METHODS: Patients with CHB infection who underwent liver biopsy to assess liver fibrosis were consecutively included. 2D-SWE confirmation thresholds with a positive likelihood ratio ≥10 and 2D-SWE exclusion thresholds with a negative likelihood ratio ≤0.1 were identified to rule in or rule out significant fibrosis and cirrhosis, respectively. RESULTS: The first 515 patients (index cohort) and the next 421 patients (validation cohort) were included in the final analysis. The low and high cut-offs to rule out and rule in patients with significant fibrosis (≥ F2) were 5.4 kPa and 9.0 kPa, respectively, in patients with ALT levels ≤ 2 × the upper limit of normal (ULN) and 7.1 kPa and 11.2 kPa in patients with ALT levels > 2 × ULN. For cirrhosis (F4), the corresponding values were 8.1 kPa and 12.3 kPa in patients with ALT levels ≤ 2 × ULN and 11.9 kPa and 24.7 kPa in patients with ALT levels > 2 × ULN. The dual cut-off values showed an overall accuracy of more than 90% for diagnosis of the presence or absence of significant fibrosis and cirrhosis in the index and validation cohorts. There were no significant differences in the accuracy values between the cohorts (all p>0.05). CONCLUSION: The ALT-adapted dual cut-offs of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis in patients with CHB infection. KEY POINTS: • The ALT-adapted dual cut-off values of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis. • ALT levels did not influence the overall diagnostic accuracy for predicting significant fibrosis and cirrhosis. • The ALT-adapted dual cut-offs in patients with ALT levels > 2 × ULN were markedly higher than those in patients with ALT levels ≤ 2 × ULN.

Potential application of ultrasound-guided thermal ablation in rare liver tumors.

BACKGROUND: With the advances of imaging techniques, the detection rate of rare liver tumor is increased. However, the therapeutic strategies of the rare liver tumors remain limited. METHODS: We analyzed twelve pathologically confirmed rare liver tumors in 8 patients. All of the patients underwent ultrasound (US) guided biopsy and subsequent thermal ablation. The tumors were ablated according to the preoperative plans and monitored by real-time US. CT/MRI fused with contrast enhanced US (CEUS) or three-dimensional (3D) US-CEUS images were used to guide and assess the ablation zone more accurately during thermal ablation. The rate of technical efficacy was assessed based on the contrast-enhance CT/MRI (CECT/MRI) results one month after ablation. Local tumor progression (LTP), recurrence and complications were followed up and recorded. RESULTS: Among these twelve nodules, nine were subject to US-guided thermal ablation, whereas the other three inconspicuous nodules were subject to CEUS-guided thermal ablation. Intra-procedure CT/MRI-CEUS or 3D US-CEUS fusion imaging assessments demonstrated that the ablation zone sufficiently covered the original tumor, and no immediate supplementary ablation was required. Additionally, no major complications were observed during the follow-up period. The postoperative CECT/MRI confirmed that the technique success rate was 100%. Within the surveillance period of 13 months, no LTP or recurrence was noted. CONCLUSIONS: US-guided thermal ablation was feasible and safe for rare liver tumors. The use of fusion imaging technique might make US-guided thermal ablation as effective as surgical resection, and this technique might serve as a potential therapeutic modality for rare liver tumors in the future.

2D shear wave elastography combined with MELD improved prognostic accuracy in patients with acute-on-chronic hepatitis B liver failure.

OBJECTIVES: To evaluate accuracy of two-dimensional shear wave elastography (2D SWE) and develop and validate a new prognostic score in predicting prognosis of acute-on-chronic liver failure (ACLF) patients. METHODS: From 1 October 2013 to 30 September 2015, we consecutively enrolled 290 patients, sequentially collected data (including 2D SWE, ultrasound parameters, laboratory data and prognostic scores) and recorded patients' outcome (recovering/steady or worsening) during a 90-day follow-up period. We evaluated ability of 2D SWE to predict outcomes of acute-on-chronic hepatitis B liver failure (ACLF-HBV) patients. We developed a new score (MELD-SWE, combining MELD and SWE values) for predicting mortality risk of ACLF-HBV in 179 patients in a derivation group, and validated in 111 patients. RESULTS: 2D SWE values were higher in worsening patients than recovering/steady ones (p < 0.001). Accuracy of 2D SWE in predicting outcomes of ACLF-HBV was comparable to that of the MELD score (p = 0.441). MELD-SWE showed a significantly higher prognostic value than MELD in both derivation (AUROC, 0.80 vs. 0.76, p = 0.040) and validation (AUROC, 0.87 vs. 0.82, p = 0.018) group. CONCLUSIONS: The MELD-SWE score, combining MELD and SWE values, was superior to MELD alone for outcoming prediction in patients with ACLF-HBV. KEY POINTS: • 2D SWE is a simple prognostic evaluation tool in patients with ACLF-HBV. • MELD-SWE was created in this study: 1.3×MELD + 0.3×2D SWE (kPa). • MELD-SWE score was superior to MELD alone for outcoming prediction in ACLF-HBV. • In this study, 46.8 was the optimal cut-off value of MELD-SWE score.

Immediate evaluation and guidance of liver cancer thermal ablation by three-dimensional ultrasound/contrast-enhanced ultrasound fusion imaging.

PURPOSE: To investigate the feasibility and value of three-dimensional ultrasound/contrast-enhanced ultrasound (3D US-CEUS) fusion imaging for the immediate evaluation of technical success and the guidance of supplementary ablation during the liver cancer thermal ablation procedure. MATERIALS AND METHODS: Patients diagnosed with malignant liver cancer intending to receive thermal ablation including radiofrequency ablation (RFA) or microwave ablation (MWA) were enrolled. 3D US-CEUS fusion imaging was used to immediately assess the technical success and guide supplementary ablation. Contrast-enhanced computed tomography/magnetic resonance imaging (CECT/CEMRI) was performed one month after ablation to assess the technique effectiveness of the ablation. The registration success rate, duration time of 3D US-CEUS fusion imaging, technique effectiveness rate and major complications were recorded. RESULTS: In total, 76 patients with 95 tumours who underwent RFA or MWA and assessed by 3D US-CEUS fusion imaging were enrolled. The registration success rate of 3D US-CEUS fusion imaging was 93.7% (89/95), and the duration time was 4.0 ± 1.1 min. Thirty lesions received supplementary ablation immediately during the procedure. The technique effectiveness rate of the ablation was 98.8% (81/82). There were no major complications related to ablation. CONCLUSIONS: 3D US-CEUS fusion imaging is a feasible and valuable technique for the immediate evaluation and guidance of supplementary ablation during the liver cancer thermal ablation procedure.

Tardus parvus waveforms in Doppler ultrasonography for hepatic artery stenosis after liver transplantation: can a new cut-off value guide the next step?

PURPOSE: Considering the high false-positive diagnosis of the tardus parvus waveform (TPW) in Doppler ultrasonography (DUS) for hepatic artery stenosis (HAS) after liver transplantation (LT), this study aimed to determine clinical features and new cut-off values to help guide treatment. MATERIALS AND METHODS: This retrospective study was approved by an Institutional Review Board. A total of 171 LT recipients were included and underwent DUS and either computed tomography angiography or digital subtraction angiography with an interval < 4 weeks at least 1 month post-LT. The DUS of 69 patients exhibited TPW [defined as resistive index (RI) < 0.5 and systolic acceleration time (SAT) > 0.08 s]. A multilevel likelihood ratio (LR) analysis was used to explore new cut-off values for DUS. In addition, abnormal liver function was considered additional evidence (defined as any liver enzyme > 3-fold of the upper limit of normal level or 2-fold increased). The results were stratified into three categories, category 1 (subjects with traditional TPW), category 2 (subjects with traditional TPW and abnormal liver function), and category 3 (subjects with traditional TPW and abnormal liver function, or with new cut-off values), and the diagnostic performance of each category was analyzed. RESULTS: The LR analysis revealed new cut-off values of RI < 0.4 (LR = 10.58) or SAT > 0.12 s (LR = 16.46). The false-positive rates for categories 2 and 3 were significantly lower (7.6% vs. 18.1%, P = 0.038; 1.9% vs. 18.1%, P < 0.001, respectively) than those for category 1, while the sensitivity for category 2 was significantly lower (41.8% vs. 74.6%, P < 0.001; 41.8% vs. 61.2%, P = 0.038, respectively) than that for categories 1 and 3. CONCLUSION: Using either (1) RI < 0.4 or SAT > 0.12 s, or (2) traditional TPW (RI < 0.5 and SAT > 0.08 s) in the presence of abnormal liver functions as the DUS criteria for HAS will significantly decrease the false-positive rate compared to traditional TPW without a significant increase in the false-negative rate.