Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study.

BACKGROUND: Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. METHODS: A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, ß stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson's correlation, multiple linear regression, and analyses of covariance. RESULTS: All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The ß stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 µm/year in women and 5.8 µm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. CONCLUSIONS: The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

A combined model based on radiomics features of Sonazoid contrast-enhanced ultrasound in the Kupffer phase for the diagnosis of well-differentiated hepatocellular carcinoma and atypical focal liver lesions: a prospective, multicenter study.

OBJECTIVE: The objective of this study was to develop a combined model based on radiomics features of Sonazoid contrast-enhanced ultrasound (CEUS) during the Kupffer phase and to evaluate its value in differentiating well-differentiated hepatocellular carcinoma (w-HCC) from atypical benign focal liver lesions (FLLs). METHODS: A total of 116 patients with preoperatively Sonazoid-CEUS confirmed w-HCC or benign FLL were selected from a prospective multiple study on the clinical application of Sonazoid in FLLs conducted from August 2020 to March 2021. According to the randomization principle, the patients were divided into a training cohort and a test cohort in a 7:3 ratio. Seventy-nine patients were used for establishing and training the radiomics model and combined model. In comparison, 37 patients were used for validating and comparing the performance of the models. The diagnostic efficacy of the models for w-HCC and atypical benign FLLs was evaluated using ROCs curves and decision curves. A combined model nomogram was created to assess its value in reducing unnecessary biopsies. RESULTS: Among the patients, there were 55 cases of w-HCC and 61 cases of atypical benign FLLs, including 28 cases of early liver abscess, 16 cases of atypical hepatic hemangioma, 8 cases of hepatocellular dysplastic nodules (DN), and 9 cases of focal nodular hyperplasia (FNH). The radiomics model and combined model we established had AUCs of 0.905 and 0.951, respectively, in the training cohort, and the AUCs of the two models in the test cohort were 0.826 and 0.912, respectively. The combined model outperformed the radiomics feature model significantly. Decision curve analysis demonstrated that the combined model achieved a higher net benefit within a specific threshold probability range (0.25 to 1.00). A nomogram of the combined model was developed. CONCLUSION: The combined model based on the radiomics features of Sonazoid-CEUS in the Kupffer phase showed satisfactory performance in diagnosing w-HCC and atypical benign FLLs. It can assist clinicians in timely detecting malignant FLLs and reducing unnecessary biopsies for benign diseases.

Clinical diagnostic value of contrast-enhanced ultrasound combined with microflow imaging in benign and malignant renal tumors: A retrospective cohort study.

This study aims to evaluate the clinical diagnostic value of contrast-enhanced ultrasound combined with microflow imaging (CEUS-MFI) in the differential diagnosis of benign and malignant renal tumors. All patients underwent CEUS, MFI, color doppler flow imaging (CDFI), and CEUS-MFI. The efficacies of these different diagnostic modalities in diagnosing benign and malignant renal tumors were evaluated by Kappa consistency test and the receiver operating characteristic (ROC) curve, with pathological findings serving as the gold standard. CDFI, MFI and CEUS-MFI all demonstrated higher blood flow in malignant tumors compared with benign tumors. Compared with benign tumors, CDFI detected a higher rate of punctate and linear Adler grade 2 and 3 blood flows in malignant tumors, as well as peripheral semicircular or annular blood flow. MFI identified a high rate of peripheral circumferential blood flow and irregular vascular morphology in malignant tumors, with most exhibiting Adler grade 3 blood flow. In addition, CEUS-MFI showed more dendritic or irregular Adler grade 2 or 3 blood flows in malignant renal tumors than MFI alone. Further analysis showed that CEUS-MFI had the highest consistency with pathological diagnosis (Kappa = 0.808). The ROC curve showed that the area under the curve (AUC) for CEUS-MFI in differentiating between benign and malignant lesions was 0.898, significantly outperforming other single diagnostic methods. With its capability to display microvascular information and assess overall pathological characteristics, MFI can accurately predict the nature of renal tumors and assist in surgical planning.

In-vivo assessment of a rat rectal tumor using optical-resolution photoacoustic endoscopy.

Optical-resolution photoacoustic endoscopy (OR-PAE) has been proven to realize imaging on the vascular network in the gastrointestinal (GI) tract with high sensitivity and spatial resolution, providing morphological information. Various photoacoustic endoscopic catheters were developed to improve the resolution and adaptivity of in-vivo imaging. However, this technology has not yet been validated on in-vivo GI tumors, which generally feature angiogenesis. The tumor causes thickened mucosa and neoplasia, requiring large depth-of-field (DOF) in imaging, which contradicts to high-resolution imaging. In this work, a novel catheter was developed with a high resolution of ∼27 µm, providing a matched DOF of ∼400 µm to cover the vessels up to the submucosa layer. Optical-resolution photoacoustic endoscopic imaging was first performed on in-vivo rat rectal tumors. In addition, to further characterize the vessel morphology, tumor-suspected regions and normal regions were selected for quantification and analysis of vessel dimension distribution and tortuosity. All the results suggest that the OR-PAE has great application potential in tumor diagnosis, evaluation, and monitoring of therapeutic efficacy.

Image-Guided Thermal Ablation for Hepatic Epithelioid Hemangioendothelioma: A Multicenter Experience.

PURPOSE: To investigate the feasibility, safety, and clinical outcomes of image-guided thermal ablation in patients with hepatic epithelioid hemangioendothelioma (HEHE). MATERIALS AND METHODS: This was a multicenter retrospective investigation of 18 patients (43.9 years [SD ± 14.8]; 6 men) who underwent image-guided thermal ablation for HEHE between January 2013 and February 2023. A total of 31 ablation sessions (24 involving microwave ablation and 7 involving radiofrequency ablation) were evaluated. The rates of technical success, adverse events, and outcomes were assessed. The Kaplan‒Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) rates. The risk factors affecting PFS were investigated using Cox proportional hazard regression analysis. RESULTS: The technical success rate was 93.5% (29/31). No major adverse events occurred. Local tumor progression occurred after 2 sessions (6.5%, 2/31), and intrahepatic distant metastasis occurred after 16 sessions (51.6%, 16/31). During the medium follow-up time of 37.2 months (range, 3-117 months), the OS and PFS rates were 87.6% and 62.2%, respectively, at 1 year; 75.5% and 37.4%, respectively, at 3 years; and 75.5% and 37.4%, respectively, at 5 years. The median OS and PFS were 90.5 months (95% CI: 68.1-112.8) and 23.8 months (95% CI: 15.4-32.2), respectively. According to the multivariate analysis, a larger tumor size (P = .026) was associated with shorter PFS. CONCLUSIONS: Image-guided thermal ablation is a feasible and safe treatment option for patients with HEHE that resulted in local tumor control and a favorable long-term prognosis.

A multicenter case-controlled study on laparoscopic hepatectomy versus microwave ablation as first-line therapy for 3-5 cm hepatocellular carcinoma in patients aged 60 and older.

BACKGROUND: There is currently a lack of convincing evidence for microwave ablation (MWA) and laparoscopic liver resection (LLR) for patients ≥60 years old with 3-5 cm hepatocellular carcinoma. MATERIALS AND METHODS: Patients were divided into three cohorts based on restricted cubic spline analysis: 60-64, 65-72, and ≥73 years. Propensity score matching (PSM) was performed to balance the baseline variables in a 1:1 ratio. Overall survival (OS) and disease-free survival (DFS) were assessed, followed by a comparison of complications, hospitalization, and cost. RESULTS: Among 672 patients, the median age was 66 (IQR 62-71) years. After PSM, two groups of 210 patients each were selected. During the 36.0 (20.4-52.4) month follow-up period, the 1-year, 3-year, and 5-year OS rates in the MWA group were 97.6, 80.9, and 65.3% and 95.5, 78.7, and 60.4% in the LLR group (HR 0.98, P =0.900). The corresponding DFS rates were 78.6, 49.6, and 37.5% and 82.8, 67.8, and 52.9% (HR 1.52, P =0.007). The 60-64 age cohort involved 176 patients, with no a significant difference in OS between the MWA and LLR groups (HR 1.25, P =0.370), MWA was associated with a higher recurrence rate (HR 1.94, P =0.004). A total of 146 patients were matched in the 65-72 age cohort, with no significant differences in OS and DFS between the two groups (OS (HR 1.04, P =0.900), DFS (HR 1.56, P =0.110)). In 76 patients aged ≥73 years after PSM, MWA provided better OS for patients (HR 0.27, P =0.015), and there were no significant differences in DFS between the two groups (HR 1.41, P =0.380). Taken together, for patients older than 65 years, the recurrence rate of MWA was comparable with LLR. Safety analysis indicated that LLR was associated with more postoperative bleeding ( P =0.032) and hypoproteinemia ( P =0.024). CONCLUSIONS: MWA was comparable to LLR in patients aged 65 years and older. MWA could be an alternative for the oldest old or the ill patients who cannot afford LLR, while LLR is still the first option of treatments for early-stage 3-5 cm hepatocellular carcinoma in capable elderly's.

Deep Learning of Multimodal Ultrasound: Stratifying the Response to Neoadjuvant Chemotherapy in Breast Cancer Before Treatment.

BACKGROUND: Not only should resistance to neoadjuvant chemotherapy (NAC) be considered in patients with breast cancer but also the possibility of achieving a pathologic complete response (PCR) after NAC. Our study aims to develop 2 multimodal ultrasound deep learning (DL) models to noninvasively predict resistance and PCR to NAC before treatment. METHODS: From January 2017 to July 2022, a total of 170 patients with breast cancer were prospectively enrolled. All patients underwent multimodal ultrasound examination (grayscale 2D ultrasound and ultrasound elastography) before NAC. We combined clinicopathological information to develop 2 DL models, DL_Clinical_resistance and DL_Clinical_PCR, for predicting resistance and PCR to NAC, respectively. In addition, these 2 models were combined to stratify the prediction of response to NAC. RESULTS: In the test cohort, DL_Clinical_resistance had an AUC of 0.911 (95%CI, 0.814-0.979) with a sensitivity of 0.905 (95%CI, 0.765-1.000) and an NPV of 0.882 (95%CI, 0.708-1.000). Meanwhile, DL_Clinical_PCR achieved an AUC of 0.880 (95%CI, 0.751-0.973) and sensitivity and NPV of 0.875 (95%CI, 0.688-1.000) and 0.895 (95%CI, 0.739-1.000), respectively. By combining DL_Clinical_resistance and DL_Clinical_PCR, 37.1% of patients with resistance and 25.7% of patients with PCR were successfully identified by the combined model, suggesting that these patients could benefit by an early change of treatment strategy or by implementing an organ preservation strategy after NAC. CONCLUSIONS: The proposed DL_Clinical_resistance and DL_Clinical_PCR models and combined strategy have the potential to predict resistance and PCR to NAC before treatment and allow stratified prediction of NAC response.

Present and future of metal nanoparticles in tumor ablation therapy.

Cancer is an important factor affecting the quality of human life as well as causing death. Tumor ablation therapy is a minimally invasive local treatment modality with unique advantages in treating tumors that are difficult to remove surgically. However, due to its physical and chemical characteristics and the limitation of equipment technology, ablation therapy cannot completely kill all tumor tissues and cells at one time; moreover, it inevitably damages some normal tissues in the surrounding area during the ablation process. Therefore, this technology cannot be the first-line treatment for tumors at present. Metal nanoparticles themselves have good thermal and electrical conductivity and unique optical and magnetic properties. The combination of metal nanoparticles with tumor ablation technology, on the one hand, can enhance the killing and inhibiting effect of ablation technology on tumors by expanding the ablation range; on the other hand, the ablation technology changes the physicochemical microenvironment such as temperature, electric field, optics, oxygen content and pH in tumor tissues. It helps to stimulate the degree of local drug release of nanoparticles and increase the local content of anti-tumor drugs, thus forming a synergistic therapeutic effect with tumor ablation. Recent studies have found that some specific ablation methods will stimulate the body's immune response while physically killing tumor tissues, generating a large number of immune cells to cause secondary killing of tumor tissues and cells, and with the assistance of metal nanoparticles loaded with immune drugs, the effect of this anti-tumor immunotherapy can be further enhanced. Therefore, the combination of metal nanoparticles and ablative therapy has broad research potential. This review covers common metallic nanoparticles used for ablative therapy and discusses in detail their characteristics, mechanisms of action, potential challenges, and prospects in the field of ablation.

Comparing Long-Term survival benefits of hepatocellular carcinoma between thermal ablation monotherapy and combined therapy with transarterial Chemoembolization: A propensity score matched study.

PURPOSE: To compare the long-term survival benefits of hepatocellular carcinoma (HCC) in thermal ablation (TA) monotherapy and TA combined with transarterial chemoembolization (TACE) using propensity score matching (PSM). MATERIALS AND METHODS: Between 1 January 2015 and 28 February 2021, 432 consecutive patients (357 men, 75 women; age range, 20-87 years) with HCC (Barcelona Clinic Liver Cancer stage 0-B) underwent ultrasonography-guided percutaneous TA, which included radiofrequency ablation (n = 340) and microwave ablation (n = 92). The association between combined treatment of TACE prior to TA versus TA monotherapy and survival prognosis was evaluated, including (a) local tumor progression (LTP) by using a logistic regression model, and (b) disease-free survival (DFS) and (c) overall survival (OS) by using a Cox proportional hazards model according to propensity score matched data. RESULTS: After PSM, the final matched cohort consisted of 146 patients, with 73 receiving TA monotherapy and 73 receiving TA combined with TACE. The cumulative LTP rates did not show a significant difference between the two groups (P = 0.960). Neither the DFS nor OS rate was significantly different between the two groups (P = 0.070 and P = 0.680, respectively). The multivariate analysis identified two significant findings. Firstly, ultrasound echo, minimal ablative margin, and high risk of tumor burden score were found to be associated with LTP. Secondly, the type of TA, Child-Turcotte-Pugh grade, ablation time, and lymphocyte-monocyte ratio were identified as independent prognostic factors for OS. CONCLUSION: The differences in LTP, DFS, and OS rates of HCC patients were found to be statistically non-significant between TA monotherapy and TACE + TA groups. For HCC patients with BCLC stage 0-B, the combination treatment of TACE prior to TA may be not associated with long-term survival benefits relative to TA monotherapy.

On-Site Diagnostic Ability of CEUS/CT/MRI for Hepatocellular Carcinoma (2019-2022): A Multicenter Study.

OBJECTIVES: To compare the on-site diagnostic performance of contrast-enhanced ultrasound (CEUS), computed tomography (CECT), and magnetic resonance imaging (CEMRI) for hepatocellular carcinoma (HCC) across diverse practice settings. METHODS: Between May 2019 and April 2022, a total of 2085 patients with 2320 pathologically confirmed focal liver lesions (FLLs) were enrolled. Imaging reports were compared with results from pathology analysis. Diagnostic performance was analyzed in defined size, high-risk factors for HCC, and hospital volume categories. RESULTS: Three images achieved similar diagnostic performance in classifying HCC from 16 types of FLLs, including HCC ≤2.0 cm. For HCC diagnosis at low-volume hospitals and HCC with high-risk factors, the accuracy and specificity of CEUS were comparable to CECT and CEMRI, while the sensitivity of CEUS (77.4 and 89.5%, respectively) was inferior to CEMRI (87.0 and 92.8%, respectively). The diagnostic accuracy of CEUS + CEMRI and CEUS + CECT increased by 7.8 and 6.2% for HCC ≤2.0 cm, 8.0 and 5.0% for HCC with high-risk factors, and 7.4 and 5.5% for HCC at low-volume hospitals, respectively, compared with CEMRI/CECT alone. CONCLUSIONS: Compared with CECT and CEMRI, CEUS provides adequate diagnostic performance in clinical first-line applications at high-volume hospitals. Moreover, a higher diagnostic performance for HCC is achieved by combining CEUS with CECT/CEMRI compared with any single imaging technique.

Combination therapy of irreversible electroporation and cytokine-induced killer cells for treating mice bearing panc02 pancreatic-cancer xenografts.

The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via Panc02 cell-bearing mouse model in vivo. CIK cells were isolated from the spleens of Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model and the proportion of different lymphocytes was also determined. The antitumor effect of the combination of IRE and CIK cells in a PC subcutaneous-xenograft model was also investigated. The proportion of cells that were positive for CD3+CD8+ and the proportion of CD3+CD56+ cells were both significantly increased after 21 days of in vitro culture. Combined treatment of IRE and CIK cell significantly inhibited tumor growth and increased the survival rate of Panc02 cell-bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and the regulators of CIK cell proliferation.

Major complications after ultrasound-guided liver biopsy: An annual audit of a Chinese tertiary-care teaching hospital.

BACKGROUND: As ultrasound-guided percutaneous liver biopsy (PLB) has become a standard and important method in the management of liver disease in our country, a periodical audit of the major complications is needed. AIM: To determine the annual incidence of major complications following ultrasound-guided PLB and to identify variables that are significantly associated with an increased risk of major complications. METHODS: A total of 1857 consecutive cases of PLB were included in our hospital from January 2021 to December 2021. The major complication rate and all-cause 30-d mortality rate were determined. Multivariate analyses were performed by logistic regression to investigate the risk factors associated with major complications and all-cause 30-d mortality following ultrasound-guided PLB. RESULTS: In this audit of 1857 liver biopsies, 10 cases (0.53%) of major complications occurred following ultrasound-guided PLB. The overall all-cause mortality rate at 30 d after PLB was 0.27% (5 cases). Two cases (0.11%) were attributed to major hemorrhage within 7 d after liver biopsy. Fibrinogen less than 2 g/L [odds ratio (OR): 17.226; 95% confidence interval (CI): 2.647-112.102; P = 0.003], post-biopsy hemoglobin level (OR: 0.963; 95%CI: 0.942-0.985; P = 0.001), obstructive jaundice (OR: 6.698; 95%CI: 1.133-39.596; P = 0.036), application of anticoagulants/antiplatelet medications (OR: 24.078; 95%CI: 1.678-345.495; P = 0.019) and age (OR: 1.096; 95%CI: 1.012-1.187; P = 0.025) were statistically associated with the incidence of major complications after PLB. CONCLUSION: In conclusion, the results of this annual audit confirmed that ultrasound-guided PLB can be performed safely, with a major complication rate within the accepted range. Strict patient selection and peri-biopsy laboratory assessment are more important than procedural factors for optimizing the safety outcomes of this procedure.

Ultrasound identification of hepatic echinococcosis using a deep convolutional neural network model in China: a retrospective, large-scale, multicentre, diagnostic accuracy study.

BACKGROUND: Ultrasonography is the most widely used technique to diagnose echinococcosis; however, challenges in using this technique and the demand on medical resources, especially in low-income or remote areas, can delay diagnosis. We aimed to develop a deep convolutional neural network (DCNN) model based on ultrasonography to identify echinococcosis and its types, especially alveolar echinococcosis. METHODS: This retrospective, large-scale, multicentre study used ultrasound images from patients assessed at 84 hospitals in China, obtained between Jan 1, 2002, and Dec 31, 2021. Patients with a diagnosis of cystic echinococcosis, alveolar echinococcosis, or seven other types of focal liver lesions were included. We tested ResNet-50, ResNext-50, and VGG-16 as the backbone network architecture for a classification DCNN model and input the perinodular information from the ultrasound images. We trained and validated the DCNN model to diagnose and classify echinococcosis using still greyscale ultrasound images of focal liver lesions in four stages: differentiating between echinococcosis and other focal liver lesions (stage one); differentiating cystic echinococcosis, alveolar echinococcosis, and other focal liver lesions (stage two); differentiating cystic echinococcosis, alveolar echinococcosis, benign other focal liver lesions, and malignant focal liver lesions (stage three); and differentiating between active and transitional cystic echinococcosis and inactive cystic echinococcosis (stage four). We then tested the algorithm on internal, external, and prospective test datasets. The performance of DCNN was also compared with that of 12 radiologists recruited between Jan 15, 2022, and Jan 28, 2022, from Qinghai, Xinjiang, Anhui, Henan, Xizang, and Beijing, China, with different levels of diagnostic experience for echinococcosis and other focal liver lesions in a subset of ultrasound data that were randomly chosen from the prospective test dataset. The study is registered at ClinicalTrials.gov (NCT03871140). FINDINGS: The study took place between Jan 1, 2002, and Dec 31, 2021. In total, to train and test the DCNN model, we used 9631 liver ultrasound images from 6784 patients (2819 [41·7%] female patients and 3943 [58·3%] male patients) from 87 Chinese hospitals. The DCNN model was trained with 6328 images, internally validated with 984 images, and tested with 2319 images. The ResNet-50 network architecture outperformed VGG-16 and ResNext-50 and was generalisable, with areas under the receiver operating characteristic curve (AUCs) of 0·982 (95% CI 0·960-0·994), 0·984 (0·972-0·992), and 0·913 (0·886-0·935) in distinguishing echinococcosis from other focal liver lesions; 0·986 (0·966-0·996), 0·962 (0·946-0·975), and 0·900 (0·872-0·924) in distinguishing alveolar echinococcosis from cystic echinococcosis and other focal liver lesions; and 0·974 (0·818-1·000), 0·956 (0·875-0·991), and 0·944 (0·844-0·988) in distinguishing active and transitional cystic echinococcosis from inactive echinococcosis in the three test datasets. Specifically, in patients with the hepatitis B or hepatitis C virus, the model could distinguish alveolar echinococcosis from hepatocellular carcinoma with an AUC of 0·892 (0·812-0·946). In identifying echinococcosis, the model showed significantly better performance compared with senior radiologists from a high-endemicity area (AUC 0·942 [0·904-0·967] vs 0·844 [0·820-0·866]; p=0·027) and improved the diagnostic ability of junior, attending, and senior radiologists before and after assistance with AI with comparison of AUCs of 0·743 (0·714-0·770) versus 0·850 (0·826-0·871); p<0·0001, 0·808 (0·782-0·832) versus 0·886 (0·864-0·905); p<0·0001, and 0·844 (0·820-0·866) versus 0·870 (0·847-0·890); p=0·092, respectively. INTERPRETATION: The DCNN model was shown to be accurate and robust, and could improve the ultrasound diagnostic ability of radiologists for echinococcosis and its types for highly endemic and remote regions. FUNDING: National Natural Science Foundation of China and National Key Research & Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Nomogram based on Sonazoid contrast-enhanced ultrasound to differentiate intrahepatic cholangiocarcinoma and poorly differentiated hepatocellular carcinoma: a prospective multicenter study.

OBJECTIVES: The aim of this study was to develop a predictive model based on Sonazoid contrast-enhanced ultrasound (SCEUS) and clinical features to discriminate poorly differentiated hepatocellular carcinoma (P-HCC) from intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHOD: Forty-one ICC and forty-nine P-HCC patients were enrolled in this study. The CEUS LI-RADS category was assigned according to CEUS LI-RADS version 2017. Based on SCEUS and clinical features, a predicated model was established. Multivariate logistic regression analysis and LASSO logistic regression were used to identify the most valuable features, 400 times repeated 3-fold cross-validation was performed on the nomogram model and the model performance was determined by its discrimination, calibration, and clinical usefulness. RESULTS: Multivariate logistic regression and LASSO logistic regression indicated that age (> 51 y), viral hepatitis (No), AFP level (≤  20 µg/L), washout time (≤  45 s), and enhancement level in the Kupffer phase (Defect) were valuable predictors related to ICC. The area under the receiver operating characteristic (AUC) of the nomogram was 0.930 (95% CI: 0.856-0.973), much higher than the subjective assessment by the sonographers and CEUS LI-RADS categories. The calibration curve showed that the predicted incidence was more consistent with the actual incidence of ICC, and 400 times repeated 3-fold cross-validation revealed good discrimination with a mean AUC of 0.851. Decision curve analysis showed that the nomogram could increase the net benefit for patients. CONCLUSIONS: The nomogram based on SCEUS and clinical features can effectively differentiate P-HCC from ICC.

Simultaneous Delivery of Dual Inhibitors of DNA Damage Repair Sensitizes Pancreatic Cancer Response to Irreversible Electroporation.

Pancreatic ductal adenocarcinoma (PDAC) is an abysmal disease refractory to most standard therapies. Irreversible electroporation (IRE) is a local ablative technique for the clinical treatment of solid tumors, including locally advanced and unresectable PDAC, by intratumorally delivering high-intensity electric pulses to permanently disrupt cell membranes and induce cell death. But the distribution of electric field is uneven within the tumor, and in some regions, tumor cells only experience temporary perturbation to their cell membrane, a phenomenon denoted as reversible electroporation (RE). These tumor cells may survive and therefore are the main culprit of tumor relapse after IRE. We herein showed that RE, although not killing tumor cells, induced DNA double-strand breaks and activated DNA damage repair (DDR) responses. Using reactive oxygen species-sensitive polymeric micelles coloaded with Olaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), and AZD0156, an inhibitor of ataxia telangiectasia mutated (ATM), the resultant nanoformulation (M-TK-OA) disrupted both homologous recombination and nonhomologous end joining signaling of the DDR response and impaired colony formation in pancreatic cancer cells after RE. The combination of IRE and M-TK-OA significantly prolonged animal survival in both subcutaneous and orthotopic murine PDAC models and elicited CD8+ T cell-mediated antitumor immunity with a sustained antitumor memory. The efficacy of combined IRE and M-TK-OA treatments was partially attributed to the activation of cyclic GMP-AMP synthase-stimulator of interferon genes innate immune responses. Our study suggests that dual inhibition of PARP and ATM with nanomedicine is a promising strategy to enhance the pancreatic cancer response to IRE.

Safety and efficacy of microwave ablation for the treatment of low-risk papillary thyroid microcarcinoma: a prospective multicenter study.

OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.

Cell-cycle dependent nuclear gene delivery enhances the effects of E-cadherin against tumor invasion and metastasis.

Gene delivery is the process by which foreign DNA is transferred to host cells, released from intracellular vesicles, and transported to the nuclei for transcription. This process is frequently inefficient and difficult to control spatiotemporally. We developed a gene delivery strategy that uses ultrasound to directly deliver plasmid DNA into nuclei via gas vesicles (GVs)-based intracellular cavitation. pDNA-binding GVs can be taken up by cells and cause intracellular cavitation when exposed to acoustic irradiation and delivering their pDNA payloads into nuclei. Importantly, GVs can remain stable in the cytoplasm in the absence of acoustic irradiation, allowing for temporally controlled nuclear gene delivery. We were able to achieve spatiotemporal control of E-cadherin nuclear gene delivery in this manner, demonstrating its efficacy in tumor invasion and metastasis inhibition. Interestingly, we discovered that nuclear gene delivery of E-cadherin during the G2/M phase of the cell cycle in C6 tumor cells inhibited tumor invasion and metastasis more effectively than during the G1 and S phases. The gene delivery of E-cadherin at the G2/M phase resulted in significantly lower expression of Fam50a, which reduced Fam50a/Runx2 interaction and led to reduced transactivation of MMP13, an important factor for epithelial-mesenchymal transition, as observed in a molecular mechanism assay. Thus, using remote acoustic control of intracellular cavitation of pDNA-GVs, we developed a high spatiotemporally controllable gene delivery strategy and achieved stronger tumor invasion and metastasis inhibition effects by delivering the E-cadherin gene at the G2/M phase.