Contrast-enhanced US with Perfluorobutane to Diagnose Small Lateral Cervical Lymph Node Metastases of Papillary Thyroid Carcinoma.

Background Although metastasis of lateral cervical lymph nodes (LNs) is common in papillary thyroid carcinoma (PTC), correctly diagnosing small metastatic LNs with US remains challenging. The use of contrast-enhanced US (CEUS), especially the postvascular phase of CEUS with perfluorobutane contrast material, might contribute to improved diagnosis of metastatic LNs in PTC. Purpose To assess the diagnostic value of the postvascular phase of CEUS with perfluorobutane in suspicious small lateral cervical LNs (short-axis diameter ≤8 mm) in patients with PTC. Materials and Methods This single-center study prospectively enrolled consecutive participants with confirmed PTC and suspicious LNs at US from October 2020 to October 2021. All participants underwent CEUS, 1 week before biopsy or surgery, with intravenous perfluorobutane contrast material to visualize the LNs in the vascular phase (5-60 seconds after injection) and postvascular phase (10-30 minutes after injection). The reference standard was cytologic and surgical histologic assessment of the LNs. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of sonographic features were calculated, and the diagnostic performance of US, CEUS, and the combination of postvascular phase and US features was assessed using multivariable logistic regression models. Results A total of 135 participants (median age, 36 years [IQR, 30-46 years]; 100 women) with 161 suspicious LNs at US were evaluated, including 67 metastatic and 94 benign LNs. The specificity of perfusion defect as a sonographic feature in the vascular phase reached 96% (90 of 94 LNs), and the negative predictive value of non-isoenhancement (ie, hypoenhancement, partial enhancement, and no enhancement) in the postvascular phase reached 100% (83 of 83 LNs). The area under the receiver operating characteristic curve (AUC) of the combination of postvascular phase and US features was 0.94 (95% CI: 0.89, 0.97), significantly higher than that of US features alone (AUC, 0.73; 95% CI: 0.65, 0.79; P < .001). Conclusion The postvascular phase of CEUS with perfluorobutane demonstrated excellent performance for diagnosing suspicious small lateral cervical LNs in participants with PTC. Published under a CC BY 4.0 license Supplemental material is available for this article. See also the editorial by Gunabushanam in this issue.

Comparison of diagnostic accuracy and utility of artificial intelligence-optimized ACR TI-RADS and original ACR TI-RADS: a multi-center validation study based on 2061 thyroid nodules.

OBJECTIVE: To determine if artificial intelligence-based modification of the Thyroid Imaging Reporting Data System (TI-RADS) would be better than the current American College of Radiology (ACR) TI-RADS for risk stratification of thyroid nodules. METHODS: A total of 2061 thyroid nodules (in 1859 patients) sampled with fine-needle aspiration or operation were retrospectively analyzed between January 2017 and July 2020. Two radiologists blinded to the pathologic diagnosis evaluated nodule features in five ultrasound categories and assigned TI-RADS scores by both ACR TI-RADS and AI TI-RADS. Inter-rater agreement was assessed by asking another two radiologists to score a set of 100 nodules independently. The reference standard was postoperative pathological or cytopathological diagnosis according to the Bethesda system. Inter-rater agreement was determined using intraclass correlation coefficient (ICC). RESULTS: AI TI-RADS assigned lower TI-RADS risk levels than ACR TI-RADS (p < 0.001) and had larger area under receiver operating characteristic curve (0.762 vs. 0.679, p < 0.001). The sensitivities of ACR TI-RADS and AI TI-RADS were similar (86.7% vs. 82.2%, p = 0.052), but specificity was higher with AI TI-RADS (70.2% vs. 49.2%, p < 0.001). AI TI-RADS downgraded 743 (48.63%) benign nodules, indicating that 328 (42.3% of 776 biopsied nodules) unnecessary fine-needle aspirations (FNA) could have been avoided. Inter-rater agreement was better with AI TI-RADS than with ACR TI-RADS (ICC, 0.808 vs. 0.861, p < 0.001). CONCLUSION: AI TI-RADS can achieve meaningful reduction in the number of benign thyroid nodules recommended for biopsy and significantly improve specificity despite a slight decrease in sensitivity. KEY POINTS: • AI TI-RADS assigned lower TI-RADS risk levels than ACR TI-RADS, showing similar sensitivity but higher specificity. • Half of the benign nodules can be downgraded of which 42.3% of biopsy nodules avoided unnecessary fine-needle aspiration (FNA). • AI TI-RADS had a better overall inter-rater agreement.

The benefit of contrast-enhanced ultrasound in biopsies for focal liver lesions: a retrospective study of 820 cases.

OBJECTIVE: This study compared the performance between ultrasound (US)- and contrast-enhanced US (CEUS)-guided liver biopsies and evaluated the benefit of CEUS in percutaneous biopsy for focal liver lesions (FLLs). METHODS: We performed a retrospective study of 820 patients with FLLs, who underwent percutaneous liver biopsy in our center between 2017 and 2019. The patients were divided into two groups based on whether US (n = 362) or CEUS (n = 458) used before a biopsy. The two groups were compared based on specimen adequacy for pathological diagnosis and diagnostic accuracy of liver biopsy. Stratification analysis was performed based on lesion and protocol characteristics to provide detailed information for selecting the imaging guidance for biopsy. RESULTS: Compared with the US group, the CEUS group yielded more acceptable samples (97.6% vs. 99.4%, p < 0.05) and improved diagnostic accuracy (92.6% vs. 96.4%, p < 0.05), and achieved better sensitivity (92.5% vs. 96.2%, p < 0.05) for liver biopsies, especially in FLLs ≥ 5 cm, heterogeneous hypoechoic FLLs, or FLLs with an obscure boundary. The CEUS group showed significantly higher accuracy compared with the US group pertaining to single-puncture biopsies (100% vs. 92.7%, p < 0.05) or biopsies with punctures ≤ 2 (97.6% vs. 94.3%, p < 0.05). CONCLUSION: CEUS achieved an enhanced success rate for sampling and diagnostic accuracy of liver biopsies, especially in FLLs ≥ 5 cm, heterogeneous hypoechoic FLLs, or FLLs with an obscure boundary. CEUS can be used to decrease the number of punctures needed, which might increase the safety of liver biopsy. KEY POINTS: • CEUS can help confirm an adequate biopsy site, increasing the sampling success rate and diagnostic accuracy of the liver biopsy. • CEUS can be used to decrease the number of punctures needed to improve the safety of liver biopsy. • It is recommended to use CEUS guidance for liver biopsies, especially with FLLs ≥ 5 cm, heterogeneous hypoechoic FLLs, or FLLs with an obscure boundary.

The injury of recurrent laryngeal nerve and thyroid regeneration after irreversible electroporation ablation of most part of thyroid gland-an experimental study on swine model.

To study the thyroid regeneration and injury of recurrent laryngeal nerve after irreversible electroporation (IRE). 12 pigs were divided into three groups: six pigs underwent IRE, other pigs were used as controls. IRE was performed near tracheoesophageal groove, to ablate most part of thyroid gland. Parathyroid and thyroid function, recurrent laryngeal nerve injury and thyroid computed tomography (CT) imaging were regularly investigated. The histopathology results were analyzed to detect thyroid regeneration. Masson's trichrome method for collagen and immunohistochemistry were performed for Soluble protein-100 (S100) and neurofilaments on nerve section. In IRE group, there were no symptoms of recurrent laryngeal nerve-related injury. No abnormalities of recurrent laryngeal nerve were shown on hematoxylin-eosin (HE) staining, Masson's trichrome staining, Neurofilament (NF) staining and S100 staining. There were no significant changes for thyroid and parathyroid function in all pigs. Immediately after IRE, CT showed hypoattenuation in the ablated thyroid gland and it became swelling. 14 days after IRE, thyroid CT showed hetergenous attenuation in the electroporation zone, and the size and attenuation of thyroid gland were normal after two months. There was cell apoptosis in the thyroid gland after IRE. Seven and 14 days after IRE, there was fragmentation of nucleus within the follicle, and some follicles were empty. Two months later, complete regeneration of thyroid tissue was shown. IRE was shown to be both effective and safe with complete regeneration of thyroid tissue and preservation of the function and structure of the recurrent laryngeal nerve.

Combined percutaneous radiofrequency ablation and ethanol injection versus hepatic resection for 2.1-5.0 cm solitary hepatocellular carcinoma: a retrospective comparative multicentre study.

OBJECTIVES: To compare combined percutaneous radiofrequency ablation and ethanol injection (RFA-PEI) with hepatic resection (HR) in the treatment of resectable solitary hepatocellular carcinoma (HCC) with 2.1-5.0 cm diameter. METHODS: From June 2009 to December 2015, 271 patients whom underwent RFA-PEI (n = 141) or HR (n = 130) in three centres were enrolled. The overall survival (OS) and recurrence-free survival (RFS) between groups were compared with Kaplan-Meier method and log-rank tests. Complications, hospital stay and cost were assessed. RESULTS: The OS rates at 1, 3 and 5 years were 93.5%, 72.7%, 58.6% in RFA-PEI group and 82.3%, 57.5%, 51.8% in HR group (p = 0.021). The corresponding 1-, 3- and 5-year RFS rates were 65.8%, 41.3%, 34.3% in RFA-PEI group and 50.5%, 33.8%, 28.4% in HR group (p = 0.038). For patients with 2.1-3.0 cm tumours, the 1-, 3- and 5-year OS after RFA-PEI and HR were 98.0%, 82.3%, 74.2% and 89.4%, 65.1%, 61.9%, respectively (p = 0.024). The corresponding RFS were 79.6%, 54.7%, 45.1% in RFA-PEI group, and 57.6%, 43.9%, 31.7% in HR group, respectively (p = 0.020). RFA-PEI was superior to HR in major complication rates, length of hospital stay and cost (all p < 0.001). CONCLUSION: RFA-PEI had a survival benefit over HR in the treatment of solitary HCCs, especially for those with 2.1-3.0 cm in diameter. KEY POINTS: • RFA-PEI provided superior survival to HR in solitary HCC with 2.1-5.0 cm in diameter. • RFA-PEI is superior to HR in complications, length of hospital stay and cost. • RFA-PEI might be an alternative treatment for solitary HCC within 5.0 cm in diameter.

Combined radiofrequency ablation and ethanol injection versus repeat hepatectomy for elderly patients with recurrent hepatocellular carcinoma after initial hepatic surgery.

PURPOSE: To retrospectively compare the efficacy and safety of combined radiofrequency ablation and percutaneous ethanol injection (RFA-PEI) with repeat hepatectomy for elderly patients with initial recurrent hepatocellular carcinoma (HCC) after hepatic surgery. METHODS: From January 2009 to June 2015, 105 elderly patients (≥70 years) who underwent RFA-PEI (n = 57) or repeated hepatectomy (n = 48) for recurrent HCC ≤ 5.0 cm were included in the study. The overall survival (OS) and recurrence-free survival (RFS) were analysed with the Kaplan-Meier method and compared by the log-rank test. Non-tumour-related death, complications and hospital stays were assessed. Univariate and multivariate analyses were performed to identify the prognostic significance of the variables in predicting the OS and RFS. RESULTS: OS rates were 78.2%, 40.8% and 36.7% at 1, 3 and 5 years after RFA-PEI and 76.3%, 52.5% and 42.6% after repeat hepatectomy, respectively (p = 0.413). Correspondingly, the 1-, 3- and 5-year RFS rates after RFA-PEI and repeat hepatectomy were 69.5%, 37.8%, 33.1% and 73.1%, 49.7%, 40.7%, respectively (p = 0.465). Non-tumour-related deaths in the RFA-PEI group (2/57) were significantly fewer than those in the repeat hepatectomy group (10/48) (p = 0.016). RFA-PEI was superior to repeat hepatectomy regarding the major complication rates and length of in-hospital stay (both p < 0.001). Multivariate analysis showed that the tumour number was the significant prognostic factor for the OS (hazard ratio (HR) = 1.961, 95% CI = 1.043-3.686, p = 0.037) and RFS (HR = 1.866, 95% CI = 1.064-3.274, p = 0.030). CONCLUSION: RFA-PEI provides comparable OS and RFS to repeat hepatectomy for elderly patients with small recurrent HCC after hepatectomy but with fewer non-tumour-related deaths, major complications and shorter hospital stays.

Transvaginal Ultrasound-Guided Core Needle Biopsy of Pelvic Masses.

OBJECTIVES: This study assessed the efficacy and safety of transvaginal ultrasound (US)-guided core needle biopsy (CNB) for obtaining adequate pelvic mass samples for histologic analysis and evaluated factors that may affect biopsy success. METHODS: Two hundred cases underwent transvaginal US-guided CNBs for primary inoperable tumors, suspicion of metastases to the ovaries or peritoneum, recurrence, or other solid lesions in the pelvis. Biopsy samples were obtained from the pelvic cavity (67.0%), vaginal cuff or vaginal wall (17.5%), or peritoneal cake (15.5%). The potential influences of the biopsy site (pelvic cavity, vaginal cuff or vaginal wall, or peritoneal cake), vascularization, ascites, tumor size, and tumor type (inoperable, metastases, recurrence, or solid pelvic tumor) on the success of transvaginal US-guided CNB were evaluated by a univariate analysis. RESULTS: Adequate samples were obtained in 192 of 200 biopsies (96.0%), of which 190 yielded successful diagnoses (95.0%). The biopsy site had a significant effect on biopsy adequacy, as there was a significantly lower probability of obtaining satisfactory specimens for histologic verification from the peritoneal cake compared to pelvic tumors and the vaginal cuff or vaginal wall (P < .01). Adequacy was also affected by tumor size (P < .05) but not by vascularization, ascites, or tumor type. No complications occurred during the biopsy procedures. CONCLUSIONS: Transvaginal US-guided CNB is a safe and effective alternative to more invasive methods for evaluating pelvic lesions, such as laparoscopy and laparotomy.

Knowledge Tensor-Aided Breast Ultrasound Image Assistant Inference Framework.

Breast cancer is one of the most prevalent cancers in women nowadays, and medical intervention at an early stage of cancer can significantly improve the prognosis of patients. Breast ultrasound (BUS) is a widely used tool for the early screening of breast cancer in primary care hospitals but it relies heavily on the ability and experience of physicians. Accordingly, we propose a knowledge tensor-based Breast Imaging Reporting and Data System (BI-RADS)-score-assisted generalized inference model, which uses the BI-RADS score of senior physicians as the gold standard to construct a knowledge tensor model to infer the benignity and malignancy of breast tumors and axes the diagnostic results against those of junior physicians to provide an aid for breast ultrasound diagnosis. The experimental results showed that the diagnostic AUC of the knowledge tensor constructed using the BI-RADS characteristics labeled by senior radiologists achieved 0.983 (95% confidential interval (CI) = 0.975-0.992) for benign and malignant breast cancer, while the diagnostic performance of the knowledge tensor constructed using the BI-RADS characteristics labeled by junior radiologists was only 0.849 (95% CI = 0.823-0.876). With the knowledge tensor fusion, the AUC is improved to 0.887 (95% CI = 0.864-0.909). Therefore, our proposed knowledge tensor can effectively help reduce the misclassification of BI-RADS characteristics by senior radiologists and, thus, improve the diagnostic performance of breast-ultrasound-assisted diagnosis.

Deep Learning Model Based on Dual-Modal Ultrasound and Molecular Data for Predicting Response to Neoadjuvant Chemotherapy in Breast Cancer.

RATIONALE AND OBJECTIVES: To carry out radiomics analysis/deep convolutional neural network (CNN) based on B-mode ultrasound (BUS) and shear wave elastography (SWE) to predict response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this prospective study, 255 breast cancer patients who received NAC between September 2016 and December 2021 were included. Radiomics models were designed using a support vector machine classifier based on US images obtained before treatment, including BUS and SWE. And CNN models also were developed using ResNet architecture. The final predictive model was developed by combining the dual-modal US and independently associated clinicopathologic characteristics. The predictive performances of the models were assessed with five-fold cross-validation. RESULTS: Pretreatment SWE performed better than BUS in predicting the response to NAC for breast cancer for both the CNN and radiomics models (P < 0.001). The predictive results of the CNN models were significantly better than the radiomics models, with AUCs of 0.72 versus 0.69 for BUS and 0.80 versus 0.77 for SWE, respectively (P = 0.003). The CNN model based on the dual-modal US and molecular data exhibited outstanding performance in predicting NAC response, with an accuracy of 83.60% ± 2.63%, a sensitivity of 87.76% ± 6.44%, and a specificity of 77.45% ± 4.38%. CONCLUSION: The pretreatment CNN model based on the dual-modal US and molecular data achieved excellent performance for predicting the response to chemotherapy in breast cancer. Therefore, this model has the potential to serve as a non-invasive objective biomarker to predict NAC response and aid clinicians with individual treatments.

Dual-source dual-energy thin-section CT combined with small field of view technique for small lymph node in thyroid cancer: a retrospective diagnostic study.

BACKGROUND: To evaluate the diagnostic performance of quantitative spectral parameters derived from dual-source dual-energy CT at small field of view (FOV) for small lymph node metastasis in thyroid cancer. METHODS: This was a retrospective diagnostic study. From 2016 to 2019, 280 patients with thyroid disease underwent thin-section dual-source dual-energy thyroid CT and thyroid surgery. The data of patients with lymph nodes having a short diameter of 2-6 mm was analyzed. The quantitative dual-energy CT parameters of targeted lymph nodes were measured, and all parameters between metastatic and non-metastatic lymph nodes were compared. These parameters were then fitted to univariable and multivariable binary logistic regression models. The diagnostic role of spectral parameters was analyzed by receiver operating characteristic (ROC) curves and compared with the McNemar test. Small FOV CT images and a mathematical model were used to judge the status of lymph nodes respectively, and then compared with the golden criterion-pathological diagnosis. The cut-off value of the model was 0.4419, with a sensitivity of 90.2% and a specificity of 92.7%. RESULTS: Of the 216 lymph nodes investigated in this study, 52.3% and 23.6% had a short diameter of 2-3 and 4 mm, respectively. Multiple quantitative CT parameters were significantly different between benign and malignant lymph nodes, and binary regression analysis was performed. The mathematical model was: p=ey/(1+ ey), y=-23.119+0.033× precontrast electron cloud density +0.076× arterial phase normalized iodine concentration +2.156× arterial phase normalized effective atomic number -0.540× venous phase slope of the spectral Hounsfield unit curve +1.676× venous phase iodine concentration. This parameter model had an AUC of 92%, with good discrimination and consistency, and the diagnostic accuracy was 90.3%. The diagnostic accuracy of the CT image model was 43.1%, and for lymph nodes with a short-diameter of 2-3 mm, the diagnostic accuracy was 22.1%. CONCLUSIONS: The parameter model showed higher diagnostic accuracy than the CT image model for diagnosing small lymph node metastasis in thyroid cancer, and quantitative dual-energy CT parameters were very useful for small lymph nodes that were difficult to be diagnosed only on conventional CT images. TRIAL REGISTRATION: This study is retrospectively registered, and we have registered a prospective study (Registration number: ChiCTR2000035195; http://www.chictr.org.cn).

Development and validation of a nomogram for preoperative prediction of level VII nodal spread in papillary thyroid cancer: Radiologic-pathologic correlation.

PURPOSE: To develop and validate a diagnostic nomogram for preoperative prediction of the level VII nodal spread in papillary thyroid cancer (PTC) by incorporating CT features. METHODS: A dataset of 7896 patients experiencing thyroidectomy for thyroid cancer was collected retrospectively from two hospitals, and 300 patients were finally included in this study. The CT features of metastatic LN were extracted with a one by one match of radiologic-pathologic correlation. Multivariable binary logistic regression analysis was used to develop predicting model, and then a nomogram was developed utilizing a primary cohort of 152 patients from hospital #1. The nomogram was validated in external cohort of 62 patients from hospital #2 and an independent cohort of 86 patients from hospital #1. The performance of the nomogram was evaluated with respect to its calibration, discrimination. RESULTS: 531 LNs from 300 patients were analyzed. 42.6% LNs were > 5 mm in short diameter. A total of 7 selected CT features were significantly associated with LN status (P < 0.05), including nodular enhancement, cystic change, calcification and so on. These features were contained in the prediction nomogram. The model showed good discrimination and good calibration, with a C-index of 0.938 (95% CI, 0.913 to 0.963) and 0. 795 (95% CI, 0. 726 to 0.864) for the primary cohort and the validation cohort, respectively. Decision curve analysis demonstrated that the nomogram was clinically applicable. CONCLUSIONS: This nomogram incorporating pathologically relevant CT features has demonstrated a high diagnostic value for predicting level VII nodal spread in PTC. Our work may help thyroid surgeon to decide whether upper mediastinal lymphadenectomy should be performed, which is associated with thoracotomy or other surgery.

Value of dual-phase, contrast-enhanced CT combined with ultrasound for the diagnosis of metastasis to central lymph nodes in patients with papillary thyroid cancer.

AIMS: To evaluate the diagnostic performance of computed tomography combined with ultrasound (CT/US) in metastatic central lymph nodes (CLNs) compared with US in patients with papillary thyroid cancer (PTC). MATERIAL AND METHODS: Six-hundred patients with surgically proven PTC who underwent both US and CT examination before CLN dissection were evaluated retrospectively. All cases were divided into four subgroups according to the tumor size and number. Diagnostic performances of US, CT and CT/US were evaluated. RESULTS: Among 600 patients with CLN dissection, CT/US showed higher sensitivity (89.10%) and accuracy (83.00%) than US alone (76.06%, 76.50%). In the subgroup of solitary non-microcarcinomas, the AUC of CT/US was significantly higher than that for US alone (0.827 vs. 0.722, P < 0.05). For the subgroup of solitary or multiple microcarcinomas, the performance efficiency of CT had no obvious advantage over that of US (0.698 vs. 0.740, 0.798 vs. 0.802, P > 0.05). For the subgroup of multiple non-microcarcinomas, CT, US and US/CT had high diagnostic efficacy (AUC > 0.8, Accuracy >80%. P > 0.05), and there was no significant difference between them. CONCLUSIONS: In the subgroup of solitary non-microcarcinoma, CT combined with US provided better diagnostic efficacy, and for those cases, complementary CT examination was recommended. In other subgroups, the diagnostic efficacy of US/CT was similar to that of US alone, and there was no significant benefit from additional CT examination.

Preoperative Evaluation of Central Lymph Nodes in Papillary Thyroid Carcinoma Using High-Resolution Ultrasound and Shear-Wave Elastography.

ABSTRACT: The aim of this study was to discuss the diagnostic value of high-resolution ultrasound and virtual touch tissue imaging quantification (VTIQ) for distinguishing metastatic and benign central lymph nodes (CLNs) in patients with papillary thyroid carcinoma. This retrospective study involved 86 pathologically proven benign lymph nodes (LNs) and 118 metastatic LNs in patients with papillary thyroid carcinoma. We analyzed the sonographic features of CLNs (size, shape, distribution, hilum, echogenicity, cystic change, calcification, vascularity, shear-wave velocity [SWV]). The prevalence of sonographic features and the SWV was compared between metastatic and benign CLNs. The size, shape, margin, distribution, presence of hilum, echogenicity, calcification, and vascularity were significantly different between benign and metastatic CLNs (P < 0.05 for all). The mean maximum SWV for malignant CLNs was 3.139 ± 0.408 m/s, whereas that of benign CLNs was 2.418 ± 0.369 m/s (P < 0.05). The cutoff point of the SWV for differentiating benign and malignant LNs was 2.675 m/s. Logistic regression analysis showed that round or irregular shape, aggregation or fusion, calcification, and VTIQ value greater than 2.675 m/s of CLNs were independent risk factors for malignancy, with an odds ratio of 5.77, 3.05, 3.23, and 62.85, respectively. High-resolution ultrasound and VTIQ can provide valuable information for distinguishing metastatic from benign CLNs.

Ultrasound-Based Radiomics Analysis for Predicting Disease-Free Survival of Invasive Breast Cancer.

BACKGROUND: Accurate prediction of recurrence is crucial for personalized treatment in breast cancer, and whether the radiomics features of ultrasound (US) could be used to predict recurrence of breast cancer is still uncertain. Here, we developed a radiomics signature based on preoperative US to predict disease-free survival (DFS) in patients with invasive breast cancer and assess its additional value to the clinicopathological predictors for individualized DFS prediction. METHODS: We identified 620 patients with invasive breast cancer and randomly divided them into the training (n = 372) and validation (n = 248) cohorts. A radiomics signature was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression in the training cohort and validated in the validation cohort. Univariate and multivariate Cox proportional hazards model and Kaplan-Meier survival analysis were used to determine the association of the radiomics signature and clinicopathological variables with DFS. To evaluate the additional value of the radiomics signature for DFS prediction, a radiomics nomogram combining the radiomics signature and clinicopathological predictors was constructed and assessed in terms of discrimination, calibration, reclassification, and clinical usefulness. RESULTS: The radiomics signature was significantly associated with DFS, independent of the clinicopathological predictors. The radiomics nomogram performed better than the clinicopathological nomogram (C-index, 0.796 vs. 0.761) and provided better calibration and positive net reclassification improvement (0.147, P = 0.035) in the validation cohort. Decision curve analysis also demonstrated that the radiomics nomogram was clinically useful. CONCLUSION: US radiomics signature is a potential imaging biomarker for risk stratification of DFS in invasive breast cancer, and US-based radiomics nomogram improved accuracy of DFS prediction.

Shear wave elastography-based ultrasomics: differentiating malignant from benign focal liver lesions.

PURPOSE: Ultrasomics is a radiomics technique that extracts high-throughput quantitative data from ultrasound imaging. The aim of this study was to differentiate malignant from benign focal liver lesions (FLLs) using two-dimensional shear wave elastography (2D-SWE)-based ultrasomics. METHODS: A total of 175 FLLs in 169 patients were prospectively analyzed. The study population was divided into a training cohort (n = 122) and a validation cohort (n = 53). The maxima, minima, mean, and standard deviation of 2D-SWE measurements were expressed in kilopascals (Emax, Emin, Emean, and ESD). The ultrasonics technique was used to extract the features from the 2D-SWE images. Support vector machine was used to establish two prediction models: the ultrasomics score (ultrasomics features only) and the combined score (SWE measurements and ultrasomics features). The diagnostic performance of the models in differentiating FLLs was analyzed. RESULTS: A total of 1044 features were extracted and 15 features were selected. The AUC for the combined score, ultrasomics score, Emax, Emean, Emin and ESD were 0.94, 0.91, 0.92, 0.89, 0.67, and 0.89, respectively. The combined score had the best diagnostic performance. The sensitivity, specificity, PPV, NPV, +LR, LR of the combined score were 92.59%, 87.50%, 94.59%, 82.50%, 7.35%, and 0.09%, respectively. The decision curve analysis results showed that when the threshold probability was > 29%, the combined score showed improved benefits for patients compared to using the ultrasomics score and 2D-SWE measurements. CONCLUSION: The results of this study demonstrated that the combined score had good diagnostic accuracy in differentiating malignant from benign FLLs.

Deep learning-based artificial intelligence model to assist thyroid nodule diagnosis and management: a multicentre diagnostic study.

BACKGROUND: Strategies for integrating artificial intelligence (AI) into thyroid nodule management require additional development and testing. We developed a deep-learning AI model (ThyNet) to differentiate between malignant tumours and benign thyroid nodules and aimed to investigate how ThyNet could help radiologists improve diagnostic performance and avoid unnecessary fine needle aspiration. METHODS: ThyNet was developed and trained on 18 049 images of 8339 patients (training set) from two hospitals (the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, and Sun Yat-sen University Cancer Center, Guangzhou, China) and tested on 4305 images of 2775 patients (total test set) from seven hospitals (the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the Guangzhou Army General Hospital, Guangzhou, China; the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the First Affiliated Hospital of Sun Yat-sen University; Sun Yat-sen University Cancer Center; and the First Affiliated Hospital of Guangxi Medical University, Nanning, China) in three stages. All nodules in the training and total test set were pathologically confirmed. The diagnostic performance of ThyNet was first compared with 12 radiologists (test set A); a ThyNet-assisted strategy, in which ThyNet assisted diagnoses made by radiologists, was developed to improve diagnostic performance of radiologists using images (test set B); the ThyNet assisted strategy was then tested in a real-world clinical setting (using images and videos; test set C). In a simulated scenario, the number of unnecessary fine needle aspirations avoided by ThyNet-assisted strategy was calculated. FINDINGS: The area under the receiver operating characteristic curve (AUROC) for accurate diagnosis of ThyNet (0·922 [95% CI 0·910-0·934]) was significantly higher than that of the radiologists (0·839 [0·834-0·844]; p<0·0001). Furthermore, ThyNet-assisted strategy improved the pooled AUROC of the radiologists from 0·837 (0·832-0·842) when diagnosing without ThyNet to 0·875 (0·871-0·880; p<0·0001) with ThyNet for reviewing images, and from 0·862 (0·851-0·872) to 0·873 (0·863-0·883; p<0·0001) in the clinical test, which used images and videos. In the simulated scenario, the number of fine needle aspirations decreased from 61·9% to 35·2% using the ThyNet-assisted strategy, while missed malignancy decreased from 18·9% to 17·0%. INTERPRETATION: The ThyNet-assisted strategy can significantly improve the diagnostic performance of radiologists and help reduce unnecessary fine needle aspirations for thyroid nodules. FUNDING: National Natural Science Foundation of China and Guangzhou Science and Technology Project.

Dual Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Inhibition Elicits Antitumor Immunity and Enhances Programmed Cell Death-1 Checkpoint Blockade in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Combining anti-angiogenic therapy with immune checkpoint blockade with anti-programmed cell death-1 (PD-1) antibodies is a promising treatment for hepatocellular carcinoma (HCC). Tyrosine kinase inhibitors are well-known anti-angiogenic agents and offer potential for combination with anti-PD-1 antibodies. This study investigated the possible underlying immunomodulatory mechanisms of combined therapy. METHODS: HCC tissue samples for RNA-sequencing (RNA-seq) were obtained from patients with differential prognoses following anti-PD-1 treatment. Recombinant basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) were used to stimulate T cells following lenvatinib or sorafenib treatment, respectively. T cell function was analyzed by flow cytometry and lactate dehydrogenase assay. In vivo experiments were conducted in murine H22 and Hepa 1-6 competent models of HCC. Local immune infiltration in the tumor microenvironment (TME) was assessed using multicolor flow cytometry. Gene regulation was evaluated by RNA-seq. Microvascular density was measured by immunohistochemistry, and PD-1 ligand (PD-L1) induction was quantified by western blot. RESULTS: The baseline expression of VEGF and fibroblast growth factor (FGF) in patients with progressive disease was significantly higher than in patients achieving stable disease following anti-PD-1 treatment. VEGFA and bFGF significantly upregulated the expression of PD-1, cytotoxic T-lymphocyte-associated protein-4, and Tim-3 on T cells, while inhibiting the secretion of interferon gamma (IFNG) and granzyme B and suppressing T cell cytotoxicity. This immunosuppressive effect was reverted by lenvatinib but not sorafenib. Furthermore, dual lenvatinib/anti-PD-1 antibody therapy led to better antitumor effects than either sorafenib or fibroblast growth factor receptor (FGFR) inhibitor (BGJ398) in H22 murine models of HCC. Combined lenvatinib/anti-PD-1 treatment also led to long-term immune memory formation, while synergistically modulating the TME and enhancing the cytotoxic effect of T cells. Finally, lenvatinib inhibited PD-L1 expression on human umbilical vein endothelial cells, which improved the function of T cells. CONCLUSIONS: Inhibition of vascular endothelial growth factor receptor and FGFR augmented the efficacy of anti-PD-1 antibodies. Combined lenvatinib/anti-PD-1 treatment appears to exert antitumor activity by synergistically modulating effector T cell function in the TME and by mutually regulating tumor vessel normalization.

A case-oriented web-based training system for breast cancer diagnosis.

BACKGROUND AND OBJECTIVE: Breast cancer is still considered as the most common form of cancer as well as the leading causes of cancer deaths among women all over the world. We aim to provide a web-based breast ultrasound database for online training inexperienced radiologists and giving computer-assisted diagnostic information for detection and classification of the breast tumor. METHODS: We introduce a web database which stores breast ultrasound images from breast cancer patients as well as their diagnostic information. A web-based training system using a feature scoring scheme based on Breast Imaging Reporting and Data System (BI-RADS) US lexicon was designed. A computer-aided diagnosis (CAD) subsystem was developed to assist the radiologists to make scores on the BI-RADS features for an input case. The training system possesses 1669 scored cases, where 412 cases are benign and 1257 cases are malignant. It was tested by 31 users including 12 interns, 11 junior radiologists, and 8 experienced senior radiologists. RESULTS: This online training system automatically creates case-based exercises to train and guide the newly employed or resident radiologists for the diagnosis of breast cancer using breast ultrasound images based on the BI-RADS. After the trainings, the interns and junior radiologists show significant improvement in the diagnosis of the breast tumor with ultrasound imaging (p-value < .05); meanwhile the senior radiologists show little improvement (p-value > .05). CONCLUSIONS: The online training system can improve the capabilities of early-career radiologists in distinguishing between the benign and malignant lesions and reduce the misdiagnosis of breast cancer in a quick, convenient and effective manner.

SOX2 Promotes Cell Proliferation and Metastasis in Triple Negative Breast Cancer.

This study explored the expression, biological function and prognostic role of SOX2 in triple negative breast cancer (TNBC). Quantitative real-time PCR and immunohistochemistry were used to detect the expression of SOX2 in TNBC cell lines and clinical tissues. MTT assay, Transwell assay, flow cytometry and xenograft mouse model were used to assess the biological functions of SOX2. It was found that SOX2 was up-regulated in both TNBC cell lines and clinical tissues. High expression of SOX2 was associated with shorter overall survival and disease free survival. Moreover, inhibition of SOX2 suppressed cell proliferation and invasion, induced cell apoptosis in vitro, and suppressed tumorigenesis and metastasis in vivo. In addition, analysis of TNM stage and lymph nodes infiltration among the 237 TNBC patients by paired χ2 test showed that SOX2 was inversely correlated with tumor status, our findings provided evidence that SOX2 acts as a tumor promoter in TNBC and inhibition of SOX2 could be a potential therapeutic strategy for TNBC.