Abstract Objectives To determine the diagnostic performance and inter-reader agreement of the contrast-enhanced ultrasound liver imaging reporting and data system (CEUS-LI-RADS) for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. Methods In this prospective study, CEUS-LI-RADS categories (LR-5 for predicting HCC) were assigned by six blinded readers and compared to the definitive HCC diagnosis in patients with liver cirrhosis per the 2017 China Liver Cancer Guidelines (CLCG). CEUS features were recorded in 96 patients with 96 histology-proven lesions. The diagnostic performance of LR-5 was described by the sensitivity, specificity and accuracy. Multi-reader agreement was assessed by using intraclass correlation coefficients (ICC). Results In cirrhotic patients, the specificity of LR-5 (range: 92.7–100.0 %) was statistically higher than that of CLCG for each reader (range: 28.6–64.3 %). However, the sensitivity (range: 38.6–63.6 %) and accuracy (range: 53.4–70.7 %) were statistically lower in CEUS-LIRADS than in CLCG (sensitivity range: 88.6–100.0 %; accuracy range: 77.6–86.2 %). Only fair to moderate inter-reader agreement was achieved for the CEUS-LI-RADS category (ICC = 0.595) and washout appearance (ICC range: 0.338 to 0.555). Neither nodule-in-nodule nor mosaic architecture was observed more often in HCC (all P > 0.05), with poor inter-reader consistency for both (both ICC < 0.20). Conclusion CEUS-LI-RADS category 5 has a high specificity but a low accuracy for identifying HCC in high-risk patients. Inter-reader agreement is not satisfactory concerning CEUS-LIRADS category and washout appearance. Moreover, the clinical value of ancillary features favoring HCC is quite limited.

Background: BRAF V600E mutation was proved to be associated with thyroid cancer. Papillary thyroid carcinoma (PTC) with positive BRAF mutation might have a more aggressive behavior. We investigated the correlation of the contrast-enhanced ultrasound (CEUS) features with BRAF 600VE in PTC. Methods: The medical records of 1,199 patients with 1,315 nodules who underwent CEUS prior to fine needle aspiration (FNA) from January 2016 to March 2018 were retrospectively reviewed. The features of their enhancement were assessed from eight aspects: degree of enhancement, method of enhancement, homogeneity of enhancement, completeness of enhancement, boundary of the enhanced lesions, shape of the enhanced lesions, size of the enhanced lesions, and wash out period of the enhanced lesions. The patients then examined for the BRAF V600E mutation using specimens obtained from FNA. Results: BRAF mutations were found in 888 of 1,315 nodules. The CEUS features were significantly different between BRAF-positive and BRAF-negative nodules. The BRAF mutation positive nodules were more often with larger size, hypo-enhancement, centripetal enhancement, inhomogeneous enhancement, complete enhancement, blurred boundary, irregular shape, and with wash out period at preoperative CEUS than those without BRAF mutations (P<0.001). However, no significant correlation was showed in Spearman's rank correlation between the CEUS features and BRAF mutation, except for degree of enhancement, method pattern of enhancement, and completeness of complete enhancement. Multivariate analysis showed that centripetal (OR: 1.465, 95% CI: 1.129-1.903) and no significant enhancement (OR: 0.790, 95% CI: 0.639-0.977) were predictive for the presence of BRAF mutations. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of no significant enhancement and centripetal enhancement of CEUS for predicting BRAF mutation were 68.3%, 40.0%, 91.6%, 11.7%, and 72.4%, 35.1%, 37.8%, 70.0%, respectively. Conclusions: Our study indicated that preoperative thyroid nodule characteristics on CEUS might serve as a useful tool to BRAF mutation in PTC.

Introduction: Congenital cystic adenomatoid malformation (CCAM) is a rare developmental lung abnormality, that typically manifests in neonates and infants but rarely in adults. Ultrasound is an important method of diagnosing CCAM in neonates and infants; however, few articles have reported the value of transthoracic lung ultrasound in the diagnosis of CCAM in adults. Patient concerns: We present a case of a 34-year-old woman with a cavitary lesion in her left lower lobe, that suggested chronic inflammation. Diagnosis: The patient underwent ultrasound examination and contrast-enhanced ultrasound-guided transthoracic core biopsy; histology suggested the diagnosis of lung hamartoma. Surgical resection of the lesion followed by histopathological analysis confirmed the diagnosis of CCAM. Interventions: The patient underwent transthoracic core biopsy under contrast-enhanced ultrasound guidance. A left lower lobectomy was then performed subsequently. Outcomes: The patient had a smooth recovery and remained asymptomatic during the 12-months of postoperative follow-up. Conclusion: We report a rare case of CCAM to suggest that transthoracic ultrasound combined with contrast-enhanced ultrasound is a safe and effective method of diagnosing the subpleural lung malformations in adults, thereby avoiding multiple radiation exposures and associated complications.

Background Pancreatic cancer remains among the most prevalent and aggressive forms of cancer. While immunotherapeutic treatment strategies have shown some promise in affected patients, the benefits of these interventions have been limited by insufficient tumor infiltration by activated T cells. Results Here, Titanium diselenide (TiSe2) nanosheets were synthesized with good stability. When exposed to ultrasound (US), the TiSe2 nanosheets served as a reliable nano-sensitizer capable of inducing large amounts of reactive oxygen species (ROS) mediating sonodynamic therapy (SDT) under hypoxic and normoxic conditions. The tumor-released TAAs induced by TiSe2 nanosheet-mediated SDT promoted immunogenic cell death (ICD) conducive to the maturation of dendritic cells (DCs), and cytokine secretion and the subsequent activation and infiltration of T cells into the tumor. Combining TiSe2-mediated SDT with anti-PD-1 immune checkpoint blockade treatment led to the efficient suppression of the growth of both primary tumor and distant tumor, while simultaneously preventing lung metastasis. These improved immunotherapeutic and anti-metastatic outcomes were associated with activated systematic antitumor immune responses, including the higher levels of DC maturation and cytokine secretion, the increased levels of CD8+ T cells and the decreased levels of Treg cells infiltrated in tumors. Conclusion TiSe2 can be used as a sonosensitizer with good efficacy and high safety to mediate efficient SDT. The combination treatment strategy comprised of TiSe2-mediated SDT and PD-1 blockade activate anti-tumor immune responses effectively thorough inducing ICD, resulting in the inhibition the growth and metastasis of tumor. The combination therapy holds promise as a novel immunotherapy-based intervention strategy for pancreatic cancer patients.