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BackgroundPleomorphic adenoma (PA), often with the benign-like imaging appearances similar to Warthin tumor (WT), however, is a potentially malignant tumor with a high recurrence rate. It is worse that pathological fine-needle aspiration cytology (FNAC) is difficult to distinguish PA and WT for inexperienced pathologists. This study employed deep learning (DL) technology, which effectively utilized ultrasound images, to provide a reliable approach for discriminating PA from WT.Methods488 surgically confirmed patients, including 266 with PA and 222 with WT, were enrolled in this study. Two experienced ultrasound physicians independently evaluated all images to differentiate between PA and WT. The diagnostic performance of preoperative FNAC was also evaluated. During the DL study, all ultrasound images were randomly divided into training (70%), validation (20%), and test (10%) sets. Furthermore, ultrasound images that could not be diagnosed by FNAC were also randomly allocated to training (60%), validation (20%), and test (20%) sets. Five DL models were developed to classify ultrasound images as PA or WT. The robustness of these models was assessed using five-fold cross-validation. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique was employed to visualize the region of interest in the DL models.ResultsIn Grad-CAM analysis, the DL models accurately identified the mass as the region of interest. The area under the receiver operating characteristic curve (AUROC) of the two ultrasound physicians were 0.351 and 0.598, and FNAC achieved an AUROC of only 0.721. Meanwhile, for DL models, the AUROC value for discriminating between PA and WT in the test set was from 0.828 to 0.908. ResNet50 demonstrated the optimal performance with an AUROC of 0.908, an accuracy of 0.833, a sensitivity of 0.736, and a specificity of 0.904. In the test set of cases that FNAC failed to provide a diagnosis, DenseNet121 demonstrated the optimal performance with an AUROC of 0.897, an accuracy of 0.806, a sensitivity of 0.789, and a specificity of 0.824.ConclusionFor the discrimination of PA and WT, DL models are superior to ultrasound and FNAC, thereby facilitating surgeons in making informed decisions regarding the most appropriate surgical approach.

PurposeTo develop a risk stratification system that can predict axillary lymph node (LN) metastasis in invasive breast cancer based on the combination of shear wave elastography (SWE) and conventional ultrasound.Materials and MethodsA total of 619 participants pathologically diagnosed with invasive breast cancer underwent breast ultrasound examinations were recruited from a multicenter of 17 hospitals in China from August 2016 to August 2017. Conventional ultrasound and SWE features were compared between positive and negative LN metastasis groups. The regression equation, the weighting, and the counting methods were used to predict axillary LN metastasis. The sensitivity, specificity, and the areas under the receiver operating characteristic curve (AUC) were calculated.ResultsA significant difference was found in the Breast Imaging Reporting and Data System (BI-RADS) category, the “stiff rim” sign, minimum elastic modulusof the internal tumor and peritumor region of 3 mm between positive and negative LN groups (p < 0.05 for all). There was no significant difference in the diagnostic performance of the regression equation, the weighting, and the counting methods (p > 0.05 for all). Using the counting method, a 0–4 grade risk stratification system based on the four characteristics was established, which yielded an AUC of 0.656 (95% CI, 0.617–0.693, p < 0.001), a sensitivity of 54.60% (95% CI, 46.9%–62.1%), and a specificity of 68.99% (95% CI, 64.5%–73.3%) in predicting axillary LN metastasis.ConclusionA 0–4 grade risk stratification system was developed based on SWE characteristics and BI-RADS categories, and this system has the potential to predict axillary LN metastases in invasive breast cancer.

PurposeNo non-invasive method can accurately determine the presence of central cervical lymph node (CCLN) metastasis in papillary thyroid cancer (PTC) until now. This study aimed to investigate factors significantly associated with CCLN metastasis and then develop a model to preoperatively predict CCLN metastasis in fine-needle aspiration (FNA) reporting suspicious papillary thyroid cancer (PTC) or PTC without lateral neck metastasis.Patients and MethodsConsecutive inpatients who were diagnosed as suspicious PTC or PTC in FNA and underwent partial or total thyroidectomy and CCLN dissection between May 1st, 2016 and June 30th, 2018 were included. The total eligible patients were randomly divided into a training set and an internal validation set with the ratio of 7:3. Univariate analysis and multivariate analysis were conducted in the training set to investigate factors associated with CCLN metastasis. The predicting model was built with factors significantly correlated with CCLN metastasis and validated in the validation set.ResultsA total of 770 patients were eligible in this study. Among them, 268 patients had histologically confirmed CCLN metastasis, while the remaining patients did not. Factors including age, BRAF mutation, multifocality, size, and capsule involvement were found to be significantly correlated with the CCLN metastasis in univariate and multivariate analysis. A model used to predict the presence CCLN metastasis based on these factors and US CCLN status yielded AUC, sensitivity, specificity and accuracy of 0.933 (95%CI: 0.905-0.960, p < 0.001), 0.816, 0.966 and 0.914 in the training set and 0.967 (95%CI: 0.943-0.991, p < 0.001), 0.897, 0.959 and 0.936 in the internal validation set.ConclusionAge, BRAF mutation, multifocality, size, and capsule involvement were independent predictors of CCLN metastasis in FNA reporting suspicious PTC or PTC without lateral neck metastasis. A simple model was successfully built and showed excellent discrimination to distinguish patients with or without CCLN metastasis.

ObjectiveTo explore the feasibility of shear wave elastography (SWE) parameters for assessing the biological behavior of breast cancer.Materials and MethodsIn this prospective study, 224 breast cancer lesions in 216 female patients were examined by B-mode ultrasound and shear wave elastography in sequence. The maximum size (Smax) of the lesion was measured by B-mode ultrasound, and then shear wave elastography was performed on this section to obtain relevant parameters, including maximum elasticity (Emax), mean elasticity (Emean), standard deviation of elasticity (SD), and the area ratio of shear wave elastography to B-mode ultrasound (AR). The relationship between SWE parameters and pathological type, histopathological classification, histological grade, lymphovascular invasion status (LVI), axillary lymph node status (ALN), and immunohistochemistry of breast cancer lesions was performed according to postoperative pathology.ResultsIn the univariate analysis, the pathological type and histopathological classification of breast cancer were not significantly associated with SWE parameters; with an increase in the histological grade of invasive ductal carcinoma (IDC), SD (p = 0.016) and Smax (p = 0.000) values increased. In the ALN-positive group, Smax (p = 0.004) was significantly greater than in the ALN-negative group; Smax (p = 0.003), Emax (p = 0.034), and SD (p = 0.045) were significantly higher in the LVI-positive group than in the LVI-negative group; SD (p = 0.043, p = 0.047) and Smax (p = 0.000, p = 0.000) were significantly lower in the ER+ and PR+ groups than in the ER- and PR- groups, respectively; AR (p = 0.032) was significantly higher in the ER+ groups than in the ER- groups, and Smax (p = 0.002) of the HER2+ group showed higher values than that of the HER2- group; Smax (p = 0.000), SD (p = 0.006), and Emax (p = 0.004) of the Ki-67 high-expression group showed significantly higher values than those of the Ki-67 low-expression group. In the multivariate analysis, Ki-67 was an independent factor of Smax (p = 0.005), Emax (p = 0.004), and SD (p = 0.006); ER was an independent influencing factor of Smax (p = 0.000) and AR (p = 0.032). LVI independently influences Smax (p = 0.006).ConclusionsThe SWE parameters Emax, SD, and AR can be used to evaluate the biological behavior of breast cancer.

BackgroundPapillary thyroid carcinoma (PTC) is characterized by frequent metastases to cervical lymph nodes (CLNs), and the presence of lymph node metastasis at diagnosis has a significant impact on the surgical approach. Therefore, we established a radiomic signature to predict the CLN status of PTC patients using preoperative thyroid ultrasound, and investigated the association between the radiomic features and underlying molecular characteristics of PTC tumors.MethodsIn total, 270 patients were enrolled in this prospective study, and radiomic features were extracted according to multiple guidelines. A radiomic signature was built with selected features in the training cohort and validated in the validation cohort. The total protein extracted from tumor samples was analyzed with LC/MS and iTRAQ technology. Gene modules acquired by clustering were chosen for their diagnostic significance. A radiogenomic map linking radiomic features to gene modules was constructed with the Spearman correlation matrix. Genes in modules related to metastasis were extracted for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and a protein-protein interaction (PPI) network was built to identify the hub genes in the modules. Finally, the screened hub genes were validated by immunohistochemistry analysis.ResultsThe radiomic signature showed good performance for predicting CLN status in training and validation cohorts, with area under curve of 0.873 and 0.831 respectively. A radiogenomic map was created with nine significant correlations between radiomic features and gene modules, and two of them had higher correlation coefficient. Among these, MEmeganta representing the upregulation of telomere maintenance via telomerase and cell-cell adhesion was correlated with ‘Rectlike’ and ‘deviation ratio of tumor tissue and normal thyroid gland’ which reflect the margin and the internal echogenicity of the tumor, respectively. MEblue capturing cell-cell adhesion and glycolysis was associated with feature ‘minimum calcification area’ which measures the punctate calcification. The hub genes of the two modules were identified by protein-protein interaction network. Immunohistochemistry validated that LAMC1 and THBS1 were differently expressed in metastatic and non-metastatic tissues (p=0.003; p=0.002). And LAMC1 was associated with feature ‘Rectlike’ and ‘deviation ratio of tumor and normal thyroid gland’ (p

BackgroundThe rate of carcinoma upgrade for atypical ductal hyperplasia (ADH) diagnosed on core needle biopsy (CNB) is variable on open excision. The purpose of the present study was to develop and validate a simple-to-use nomogram for predicting the upgrade of ADH diagnosed with ultrasound (US)-guided core needle biopsy in patients with US-detected breast lesions.MethodsTwo retrospective sets, the training set (n = 401) and the validation set (n = 186), from Fudan University Shanghai Cancer Center between January 2014 and December 2019 were retrospectively analyzed. Clinicopathological and US features were selected using univariate and multivariable logistic regression, and the significant features were incorporated to build a nomogram model. Model discrimination and calibration were assessed in the training set and validation set.ResultsOf the 587 ADH biopsies, 67.7% (training set: 267/401, 66.6%; validation set: 128/186, 68.8%) were upgraded to cancers. In the multivariable analysis, the risk factors were age [odds ratio (OR) 2.739, 95% confidence interval (CI): 1.525–5.672], mass palpation (OR 3.008, 95% CI: 1.624–5.672), calcifications on US (OR 4.752, 95% CI: 2.569–9.276), ADH extent (OR 3.150, 95% CI: 1.951–5.155), and suspected malignancy (OR 4.162, CI: 2.289–7.980). The model showed good discrimination, with an area under curve (AUC) of 0.783 (95% CI: 0.736–0.831), and good calibration (p = 0.543). The application of the nomogram in the validation set still had good discrimination (AUC = 0.753, 95% CI: 0.666–0.841) and calibration (p = 0.565). Instead of surgical excision of all ADHs, if those categorized with the model to be at low risk for upgrade were surveillanced and the remainder were excised, then 63.7% (37/58) of surgeries of benign lesions could have been avoided and 78.1% (100/128) malignant lesions could be treated in time.ConclusionsThis study developed a simple-to-use nomogram by incorporating clinicopathological and US features with the overarching goal of predicting the probability of upgrade in women with ADH. The nomogram could be expected to decrease unnecessary surgery by nearly two-third and to identify most of the malignant lesions, helping guide clinical decision making with regard to surveillance versus surgical excision of ADH lesions.

BackgroundTo determine a correlation between mRNA and lncRNA signatures, sonographic features, and risk of recurrence in triple-negative breast cancers (TNBC).MethodsWe retrospectively reviewed the data from 114 TNBC patients having undergone transcriptome analysis. The risk of tumor recurrence was determined based on the correlation between transcriptome profiles and recurrence-free survival. Ultrasound (US) features were described according to the Breast Imaging Reporting and Data System. Multivariate logistic regression analysis determined the correlation between US features and risk of recurrence. The predictive value of sonographic features in determining tumor recurrence was analyzed using receiver operating characteristic curves.ResultsThree mRNAs (CHRDL1, FCGR1A, and RSAD2) and two lncRNAs (HIF1A-AS2 and AK124454) were correlated with recurrence-free survival in patients with TNBC. Among the three mRNAs, two were upregulated (FCGR1A and RSAD2) and one was downregulated (CHRDL1) in TNBCs. LncRNAs HIF1A-AS2 and AK124454 were upregulated in TNBCs. Based on these signatures, an integrated mRNA–lncRNA model was established using Cox regression analysis to determine the risk of tumor recurrence. Benign-like sonographic features, such as regular shape, circumscribed margin, posterior acoustic enhancement, and no calcifications, were associated with HIF1A-AS2 expression and high risk of tumor recurrence (P

PurposeThe positivity of sentinel lymph node (SLN) metastasis is relatively low in ductal carcinoma in situ (DCIS) patients. The aim of this study was to investigate factors associated with SLN metastasis and build a model to predict the potential risk of SLN metastasis in patients with a preoperative diagnosis of DCIS.Patients and MethodsCore needle biopsy-proved DCIS patients who underwent SLN biopsy and breast surgery were retrospectively reviewed and selected. Univariate analysis was used to identify the variables correlated with SLN metastasis. A model to predict SLN metastasis was developed using a multivariate logistic regression in the training set and then validated in an internal set.ResultsA total of 407 patients with a preoperative diagnosis of DCIS were included. Upstaging to invasive/microinvasive cancer occurred in 225 patients after surgery. SLN metastasis was found in 42 patients, including 32 patients upstaging to invasive disease, 8 to microinvasive disease, and 2 pure DCIS. Tumor size based on US examination, axillary ultrasound finding, multifocality, surgery, upstaging, and Ki-67 expression were significantly related to SLN metastasis. The model incorporating tumor size, axillary ultrasound finding and multifocality yielded an AUC of 0.805 (95% CI: 0.715–0.895, p

Purpose: This study aimed to establish and validate an ultrasound radiomics nomogram for the preoperative prediction of central lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC).Patients and Methods: The prediction model was developed in 609 patients with clinicopathologically confirmed unifocal PTC who received ultrasonography between Jan 2018 and June 2018. Radiomic features were extracted after the ultrasonography of PTC. Lasso regression model was used for data dimensionality reduction, feature selection, and radiomics signature building. The predicting model was established based on the multivariable logistic regression analysis in which the radiomics signature, ultrasonography-reported LN status, and independent clinicopathologic risk factors were incorporated, and finally a radiomics nomogram was established. The performance of the nomogram was assessed with respect to the discrimination and consistence. An independent validation was performed in 326 consecutive patients from July 2018 to Sep 2018.Results: The radiomics signature consisted of 23 selected features and was significantly associated with LN status in both primary and validation cohorts. The independent predictors in the radiomics nomogram included the radiomics signature, age, TG level, TPOAB level, and ultrasonography-reported LN status. The model showed good discrimination and consistence in both cohorts: C-index of 0.816 (95% CI, 0.808–0.824) in the primary cohort and 0.858 (95% CI, 0.849–0.867) in the validation cohort. The area under receiver operating curve was 0.858. In the validation cohort, the accuracy, sensitivity, specificity and AUC of this model were 0.812, 0.816, 0.810, and 0.858 (95% CI, 0.785–0.930), respectively. Decision curve analysis indicated the radiomics nomogram was clinically useful.Conclusion: This study presents a convenient, clinically useful ultrasound radiomics nomogram that can be used for the pre-operative individualized prediction of central LN metastasis in patients with PTC.