Predicting BRAFV600E mutations in papillary thyroid carcinoma using six machine learning algorithms based on ultrasound elastography.

The most common BRAF mutation is thymine (T) to adenine (A) missense mutation in nucleotide 1796 (T1796A, V600E). The BRAFV600E gene encodes a protein-dependent kinase (PDK), which is a key component of the mitogen-activated protein kinase pathway and essential for controlling cell proliferation, differentiation, and death. The BRAFV600E mutation causes PDK to be activated improperly and continuously, resulting in abnormal proliferation and differentiation in PTC. Based on elastography ultrasound (US) radiomic features, this study seeks to create and validate six distinct machine learning algorithms to predict BRAFV6OOE mutation in PTC patients prior to surgery. This study employed routine US strain elastography image data from 138 PTC patients. The patients were separated into two groups: those who did not have the BRAFV600E mutation (n = 75) and those who did have the mutation (n = 63). The patients were randomly assigned to one of two data sets: training (70%), or validation (30%). From strain elastography US images, a total of 479 radiomic features were retrieved. Pearson's Correlation Coefficient (PCC) and Recursive Feature Elimination (RFE) with stratified tenfold cross-validation were used to decrease the features. Based on selected radiomic features, six machine learning algorithms including support vector machine with the linear kernel (SVM_L), support vector machine with radial basis function kernel (SVM_RBF), logistic regression (LR), Naïve Bayes (NB), K-nearest neighbors (KNN), and linear discriminant analysis (LDA) were compared to predict the possibility of BRAFV600E. The accuracy (ACC), the area under the curve (AUC), sensitivity (SEN), specificity (SPEC), positive predictive value (PPV), negative predictive value (NPV), decision curve analysis (DCA), and calibration curves of the machine learning algorithms were used to evaluate their performance. ① The machine learning algorithms' diagnostic performance depended on 27 radiomic features. ② AUCs for NB, KNN, LDA, LR, SVM_L, and SVM_RBF were 0.80 (95% confidence interval [CI]: 0.65-0.91), 0.87 (95% CI 0.73-0.95), 0.91(95% CI 0.79-0.98), 0.92 (95% CI 0.80-0.98), 0.93 (95% CI 0.80-0.98), and 0.98 (95% CI 0.88-1.00), respectively. ③ There was a significant difference in echogenicity,vertical and horizontal diameter ratios, and elasticity between PTC patients with BRAFV600E and PTC patients without BRAFV600E. Machine learning algorithms based on US elastography radiomic features are capable of predicting the likelihood of BRAFV600E in PTC patients, which can assist physicians in identifying the risk of BRAFV600E in PTC patients. Among the six machine learning algorithms, the support vector machine with radial basis function (SVM_RBF) achieved the best ACC (0.93), AUC (0.98), SEN (0.95), SPEC (0.90), PPV (0.91), and NPV (0.95).

Dual-modal radiomics for predicting cervical lymph node metastasis in papillary thyroid carcinoma.

BACKGROUND: Preoperative prediction of cervical lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) is significant for surgical decision-making. OBJECTIVE: This study aims to develop a dual-modal radiomics (DMR) model based on grayscale ultrasound (GSUS) and dual-energy computed tomography (DECT) for non-invasive CLNM in PTC. METHODS: In this study, 348 patients with pathologically confirmed PTC at Jiangsu University Affiliated People's Hospital who completed preoperative ultrasound (US) and DECT examinations were enrolled and randomly assigned to training (n = 261) and test (n = 87) cohorts. The enrolled patients were divided into two groups based on pathology findings namely, CLNM (n = 179) and CLNM-Free (n = 169). Radiomics features were extracted from GSUS images (464 features) and DECT images (960 features), respectively. Pearson correlation coefficient (PCC) and the least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation were then used to select CLNM-related features. Based on the selected features, GSUS, DECT, and GSUS combined DECT radiomics models were constructed by using a Support Vector Machine (SVM) classifier. RESULTS: Three predictive models based on GSUS, DECT, and a combination of GSUS and DECT, yielded performance of areas under the curve (AUC) = 0.700 [95% confidence interval (CI), 0.662-0.706], 0.721 [95% CI, 0.683-0.727], and 0.760 [95% CI, 0.728-0.762] in the training dataset, and AUC = 0.643 [95% CI, 0.582-0.734], 0.680 [95% CI, 0.623-0.772], and 0.744 [95% CI, 0.686-0.784] in the test dataset, respectively. It shows that the predictive model combined GSUS and DECT outperforms both models using GSUS and DECT only. CONCLUSIONS: The newly developed combined radiomics model could more accurately predict CLNM in PTC patients and aid in better surgical planning.

Lung cancer with breast metastasis: a case report and review of the literature.

In this article, we present a rare case of breast metastasis of lung cancer. Chest computed tomography (CT) for a woman in her early 50s indicated right lung malignancy, multiple bone metastases, and an irregular mass in her right breast. Further inquiry into the case history revealed that the patient had been aware of the breast mass for 3 years, without respiratory symptoms. Biopsy of the breast mass suggested estrogen receptor (ER) (+), progesterone receptor (PR) (-), and human epidermal growth factor receptor 2 (HER2) (+ +) breast cancer. The patient was initially diagnosed with breast cancer with lung and bone metastasis. However, comprehensive breast cancer treatment was ineffective, and thyroid transcription factor-1 (TTF-1), napsin A, and cytokeratin 7 (CK7) were evaluated to better understand the origin of the cancer. To the best of our knowledge, this patient had the longest reported disease course from presentation with a breast lump as the first symptom to the final diagnosis of breast metastasis of lung cancer. To provide a better reference for differential diagnosis of ambiguous tumors, we also performed a systematic literature review.

Evaluation of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma Using Clinical-Ultrasound Radiomic Machine Learning-Based Model.

We aim to develop a clinical-ultrasound radiomic (USR) model based on USR features and clinical factors for the evaluation of cervical lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC). This retrospective study used routine clinical and US data from 205 PTC patients. According to the pathology results, the enrolled patients were divided into a non-CLNM group and a CLNM group. All patients were randomly divided into a training cohort (n = 143) and a validation cohort (n = 62). A total of 1046 USR features of lesion areas were extracted. The features were reduced using Pearson's Correlation Coefficient (PCC) and Recursive Feature Elimination (RFE) with stratified 15-fold cross-validation. Several machine learning classifiers were employed to build a Clinical model based on clinical variables, a USR model based solely on extracted USR features, and a Clinical-USR model based on the combination of clinical variables and USR features. The Clinical-USR model could discriminate between PTC patients with CLNM and PTC patients without CLNM in the training (AUC, 0.78) and validation cohorts (AUC, 0.71). When compared to the Clinical model, the USR model had higher AUCs in the validation (0.74 vs. 0.63) cohorts. The Clinical-USR model demonstrated higher AUC values in the validation cohort (0.71 vs. 0.63) compared to the Clinical model. The newly developed Clinical-USR model is feasible for predicting CLNM in patients with PTC.

Differentiation Between Granulomatous Lobular Mastitis and Breast Cancer Using Quantitative Parameters on Contrast-Enhanced Ultrasound.

Objective: To investigate the Contrast-enhanced ultrasound (CEUS) imaging characteristics of granulomatous lobular mastitis (GLM) and the value of differentiating GLM from breast cancer. Materials and methods: The study included 30 women with GLM (mean age 36.7 ± 5 years [SD]) and 58 women with breast cancer (mean age 48. ± 8 years [SD]) who were scheduled for ultrasound-guided tissue biopsy. All patients were evaluated with conventional US and CEUS prior to the biopsy. In both groups, the parameters of the quantitative and qualitative analysis of the CEUS were recorded and compared. The receiver-operating-characteristics curves (ROC) were created. Sensitivity, specificity, cut-off, and area under the curve (AUC) values were calculated. Results: TTP values in GLM were statistically higher than in breast cancer (mean, 27.63 ± 7.29 vs. 20.10 ± 6.11), but WIS values were lower (mean, 0.16 ± 0.05 vs. 0.28 ± 0.17). Rich vascularity was discovered in 54.45% of breast cancer patients, but only 30.00% of GLM patients had rich vascularity. The AUC for the ROC test was 0.791 and 0.807, respectively. The optimal cut-off value for TTP was 24.5s, and the WIS cut-off value was 0.185dB/s, yielding 73.33% sensitivity, 84.48% specificity, and 86.21% sensitivity, 70% specificity respectively in the diagnosis of GLM. The lesion scores reduced from 4 to 3 with the addition of CEUS for the patients with GLM. However, the scores did not change for the patients with breast cancer. Conclusion: CEUS could help distinguish GLM from breast cancer by detecting higher TTP and WIS values, potentially influencing clinical decision-making for additional biopsies.

A comparison of DP-TOF Mass Spectroscopy (MS) and Next Generation Sequencing (NGS) methods for detecting molecular mutations in thyroid nodules fine needle aspiration biopsies.

Mutations in the B-Raf proto-oncogene, serine/threonine kinase (BRAF), have been linked to a variety of solid tumors such as papillary thyroid carcinoma. The purpose of this study was to compare the DP-TOF, a DNA mass spectroscopy (MS) platform, and next-generation sequencing (NGS) methods for detecting multiple-gene mutations (including BRAFV600E) in thyroid nodule fine-needle aspiration fluid. In this study, we collected samples from 93 patients who had previously undergone NGS detection and had sufficient DNA samples remaining. The MS method was used to detect multiple-gene mutations (including BRAFV600E) in DNA remaining samples. NGS detection method was used as the standard. The MS method's overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 95.8%, 100%, 100%, and 88%, respectively in BRAFV600E gene mutation detection. With a kappa-value of 0.92 (95%CI 0.82-0.99), the level of agreement between these methods was incredibly high. Furthermore, when compared to NGS in multiple-gene detection, the MS method demonstrated higher sensitivity and specificity, 82.9% and 100%, respectively. In addition, we collected the postoperative pathological findings of 50 patients. When the postoperative pathological findings were used as the standard, the MS method demonstrated higher sensitivity and specificity, at 80% and 80%, respectively. Our findings show that the MS method can be used as an inexpensive, accurate, and dependable initial screening method to detect genes mutations and as an adjunct to clinical diagnosis.

Differential diagnosis of diffuse sclerotic thyroid papillary carcinoma and Hashimoto's thyroiditis using fine-needle aspiration cytology, BRAFV600E , and ultrasound elastography.

BACKGROUND: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) has ultrasound findings that are similar to Hashimoto's thyroiditis (HT), resulting in under-diagnosis. DSV-PTC combined with HT is also common, so early and accurate diagnosis of DSV-PTC using a variety of diagnostic techniques, including FNAC, BRAFV600E mutation detection, and ultrasound elastography, is critical. OBJECTIVE: To assess the diagnostic value of fine-needle aspiration cytology (FNAC) and BRAFV600E detection in combination with ultrasound elastography in the diagnosis of DSV-PTC. METHODS: We performed a retrospective analysis of 40 patients with pathologically confirmed DSV-PTC and 43 patients with HT admitted to our hospital's ultrasound department between January 2015 and December 2020. Preoperative FNAC, BRAFV600E mutation detection, and ultrasound elastography imaging were all performed on all patients. For a definitive diagnosis, the results of these tests were compared to postoperative pathological findings. The diagnostic value of FNAC, BRAFV600E mutation detection, ultrasound elasticity imaging, and their combination for DSV-PTC diagnosis was assessed. RESULTS: The mean elastic strain rate ratio (E1/E2) of the 40 DSV-PTC cases was 5.75 ± 2.14, while that of the 43 HT cases was 2.81 ± 1.20. The receiver operating characteristic (ROC) curve was generated using the average value of E2/E1. The area under the ROC curve was 0.910, and the optimal E2/E1 cut-off value was 4.500. When FNAC, BRAFV600E mutation detection, and ultrasound elasticity imaging detection were combined, the diagnostic sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of DSV-PTC diagnosis were 92.5%, 95.3%, 93.2%, 94.9%, and 94.0%, respectively, which were significantly higher than the single technique (p < 0.05). CONCLUSIONS: The use of FNAC, BRAFV600E mutation detection, and ultrasound elastography in combination is more helpful in establishing an accurate diagnosis of DSV-PTC than using a single diagnostic technique alone.

Radiomic Model for Determining the Value of Elasticity and Grayscale Ultrasound Diagnoses for Predicting BRAFV600E Mutations in Papillary Thyroid Carcinoma.

BRAFV600E is the most common mutated gene in thyroid cancer and is most closely related to papillary thyroid carcinoma(PTC). We investigated the value of elasticity and grayscale ultrasonography for predicting BRAFV600E mutations in PTC. Methods: 138 patients with PTC who underwent preoperative ultrasound between January 2014 and 2021 were retrospectively examined. Patients were divided into BRAFV600E mutation-free group (n=75) and BRAFV600E mutation group (n=63). Patients were randomly divided into training (n=96) and test (n=42) groups. A total of 479 radiomic features were extracted from the grayscale and elasticity ultra-sonograms. Regression analysis was done to select the features that provided the most information. Then, 10-fold cross-validation was used to compare the performance of different classification algorithms. Logistic regression was used to predict BRAFV600E mutations. Results: Eight radiomics features were extracted from the grayscale ultrasonogram, and five radiomics features were extracted from the elasticity ultrasonogram. Three models were developed using these radiomic features. The models were derived from elasticity ultrasound, grayscale ultrasound, and a combination of grayscale and elasticity ultrasound, with areas under the curve (AUC) 0.952 [95% confidence interval (CI), 0.914-0.990], AUC 0.792 [95% CI, 0.703-0.882], and AUC 0.985 [95% CI, 0.965-1.000] in the training dataset, AUC 0.931 [95% CI, 0.841-1.000], AUC 0. 725 [95% CI, 0.569-0.880], and AUC 0.938 [95% CI, 0.851-1.000] in the test dataset, respectively. Conclusion: The radiomic model based on grayscale and elasticity ultrasound had a good predictive value for BRAFV600E gene mutations in patients with PTC.

Assessing Diagnostic Value of Combining Ultrasound and MRI in Extrathyroidal Extension of Papillary Thyroid Carcinoma.

Purpose: To explore the separate diagnostic value of preoperative ultrasound (US), magnetic resonance imaging (MRI), and the combination of US and MRI in extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC). Materials and Methods: This retrospective study was approved by the Affiliated People's Hospital of Jiangsu University review board. A total of 158 PTC patients with ETE received preoperative US and MRI examination and underwent surgery between May 2014 and December 2018 in Affiliated People's Hospital of Jiangsu University. For each case, the US and MRI features of ETE were retrospectively and independently investigated by two radiologists. The clinical assessment for each case was implemented, respectively, using US imaging only, MRI only, and a combination of both modalities at three different time points with one-month intervals. Results: The diagnostic accuracies of US, MRI, and the combined set for T3 (minimal ETE) were 91.7% (88/96), 74.0% (71/96), and 97.9% (94/96), respectively, indicating a significantly different performance (P < 0.001). The diagnostic accuracies for T4 (extensive ETE) were 62.9% (39/62), 87.1% (54/62), and 93.5% (58/62), respectively. The difference between the three methods for T4 was statistically significant (P = 0.000). The diagnostic accuracies for overall ETE were 80.4% (127/158), 79.1% (125/158), and 96.2% (152/158), respectively. The difference between the three methods for ETE was statistically significant (P = 0.001). Conclusion: This study suggests that ETE can be predicted most accurately by the combination of preoperative US and MRI.

Chylous Leakage After Breast-Conserving Surgery and Axillary Clearance: Case Report and Management Strategies.

Chylous leakage is a rare complication of breast and axillary surgery. We present a case of chylous leakage inside the breast following breast-conserving surgery and axillary lymph node dissection. The majority of chylous leakages in the breast are managed with conservative measures aimed at reducing lymphatic fluid production and outflow. Surgical intervention is required in cases of conservative treatment failure and high output chylous leakage. To the best of our knowledge, this is the first case report of chyles leaks inside the breast following breast-conserving surgery that was successfully treated surgically.

Fabrication of SEBS Block Copolymer-Based Ultrasound Phantom Containing Mimic Tumors for Ultrasound-Guided Needle Biopsy Training.

The creation of various phantoms is important in medical education, especially for intern physicians who need to practice their skills. Ultrasound phantoms are particularly useful for training in ultrasound-guided needle biopsy. SEBS, or poly(styrene-ethylene-butylene-styrene), is a thermoplastic elastomer that can be used with mineral oil to make ultrasound phantoms and a tumor-like structure. SEBS block copolymer-based phantoms are inexpensive, non-toxic and shelf-stable, and are easy to modulate. Most importantly, such ultrasound phantoms have acoustic and mechanical properties similar to those of human soft tissues. The quality of ultrasound images of phantoms and mimic tumors is excellent and can be maintained even after several biopsy needle punctures, making them excellent ultrasound phantoms for physician practice as needed.

Gynecomastia with rare granulomatous lobular mastitis: a case report and literature review.

This study was performed to describe a rare case of granulomatous lobular mastitis (GLM) that was successfully treated with bromocriptine in a male patient with gynecomastia and hyperprolactinemia. A 20-year-old man presented with a 1-year history of breast enlargement and galactorrhea. Physical examination revealed bilateral breast enlargement, porous discharge, and a 3-cm left breast lump in the 10-o'clock quadrant. Magnetic resonance imaging of the brain showed a 1.2-mm pituitary tumor. Laboratory analysis revealed hyperprolactinemia with low serum testosterone and elevated prolactin and estradiol levels. The lump in the left breast was examined by ultrasonography and mammography, and a core needle biopsy revealed chronic inflammation. The patient's galactorrhea and breast lump disappeared after 3 months of treatment with bromocriptine at 2.5 mg once a day. His serum prolactin level also normalized. Following a review of this case, the patient was diagnosed with gynecomastia with hyperprolactinemia complicated by rare GLM. To the best of our knowledge, this is the first reported case of concurrent gynecomastia and GLM.

Ultrasound-Guided Thermal Ablation of Thyroid Nodules: Technicalities Progress and Clinical Applications, Especially in Malignant Thyroid Nodules.

Thyroid nodules are commonly encountered in health care practice. They are usually benign in nature, with few cases being malignant, and their detection has increased in the adult population with the help of ultrasonography. Thyroidectomy or surgery is the first-line treatment and traditional method for thyroid nodules; however, thyroidectomy leaves permanent scars and requires long-term use of levothyroxine after surgery, which makes patients more reticent to accept this treatment. Thermal ablation is a minimally-invasive technique that have been employed in the treatment of benign and malignant thyroid nodules nodules, and have been shown to be effective and safe. Several studies, including long-term, retrospective, and prospective studies, have investigated the use of ablation to treat benign thyroid nodules and malignant thyroid nodules, including papillary thyroid carcinoma. Here, we review the recent progress in thermal ablation techniques for treating benign and malignant nodules, including their technicalities, clinical applications, pitfalls and limitations, and factors that could affect treatment outcomes. Special in-depth elaboration on the recent progress of the application of thermal ablation therapy in malignant thyroid nodules.

Clinical Value of Three Combined Ultrasonography Modalities in Predicting the Risk of Metastasis to Axillary Lymph Nodes in Breast Invasive Ductal Carcinoma.

OBJECTIVE: The present study aimed to assess the clinical value of conventional ultrasound (C-US), ultrasound elastography (UE), percutaneous contrast-enhanced ultrasound (P-CUES), and the combination of these three ultrasonography modalities for evaluating the risk of axillary lymph node (ALN) metastasis in breast invasive ductal carcinoma (IDC). METHODS: This retrospective analysis included 120 patients with pathologically confirmed IDC who underwent sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Based on the gold standard of postoperative pathology, ALN pathology results were evaluated and compared with findings obtained using C-US, UE, P-CUES, and the three modalities combined. RESULTS: (1) There was a statistically significant difference between the histological grade of the tumor and the pathological condition of ALNs. (2) The difference between C-US parameters and UE score were statistically significant. The accuracy of P-CEUS localization of SLNs was 100% (96/96) when compared with localization guided by methylene blue. The difference in the distribution of the four SLN enhancement patterns was statistically significant. (3) The sensitivity, specificity, positive predictive value, and negative predictive value of C-US and UE were 75%, 71%, 58%, and 89%, and 71%, 72%, 50%, and 86%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of P-CUES were 91%, 82%, 78%, 92%, respectively. When all three modalities were combined, the sensitivity, specificity, positive predictive value, and negative predictive value were 94%, 89%, 86%, and 95%, respectively. In the detection of ALN metastasis, there was a good correlation between histopathological results and evaluations based on the three combined ultrasonography modalities (kappa: 0.82, p<0.001). CONCLUSIONS: When compared to C-US, UE, or P-CEUS alone, the combination of the three ultrasonography modalities was found to be superior in distinguishing metastatic and non-metastatic ALNs. This combined strategy may aid physicians in determining the most appropriate approach to ALN surgery as well as the prognosis of breast IDC.

A Radiomic Nomogram for the Ultrasound-Based Evaluation of Extrathyroidal Extension in Papillary Thyroid Carcinoma.

PURPOSE: To construct a sequence diagram based on radiological and clinical factors for the evaluation of extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: Between January 2016 and January 2020, 161 patients with PTC who underwent preoperative ultrasound examination in the Affiliated People's Hospital of Jiangsu University were enrolled in this retrospective study. According to the pathology results, the enrolled patients were divided into a non-ETE group and an ETE group. All patients were randomly divided into a training cohort (n = 97) and a validation cohort (n = 64). A total of 479 image features of lesion areas in ultrasonic images were extracted. The radiomic signature was developed using least absolute shrinkage and selection operator algorithms after feature selection using the minimum redundancy maximum relevance method. The radiomic nomogram model was established by multivariable logistic regression analysis based on the radiomic signature and clinical risk factors. The discrimination, calibration, and clinical usefulness of the nomogram model were evaluated in the training and validation cohorts. RESULTS: The radiomic signature consisted of six radiomic features determined in ultrasound images. The radiomic nomogram included the parameters tumor location, radiological ETE diagnosis, and the radiomic signature. Area under the curve (AUC) values confirmed good discrimination of this nomogram in the training cohort [AUC, 0.837; 95% confidence interval (CI), 0.756-0.919] and the validation cohort (AUC, 0.824; 95% CI, 0.723-0.925). The decision curve analysis showed that the radiomic nomogram has good clinical application value. CONCLUSION: The newly developed radiomic nomogram model is a noninvasive and reliable tool with high accuracy to predict ETE in patients with PTC.