Ultrasonography Findings in Ovarian Hemangiomas: Report of Three Cases and Review of the Literature.

Ovarian hemangioma is a rare ovarian tumor. The imaging manifestations were rarely mentioned in previous literatures. One of the patients came to hospital with the complaints of an elevation of CA125. Another two patients found a mass in adnexa area accidentally. The oophorectomy procedures were performed and the pathological results of ovarian hemangioma were concluded. We summarized the ultrasound features of three cases retrospectively, of which could provide more information before operation to guide a management direction. A well-defined, regular-shape solid mass in ovary could be considered the possibility of hemangioma, especially when a richly vascularized tumor with prominent blood flow is detected on color Doppler sonography.

Applying machine-learning models to differentiate benign and malignant thyroid nodules classified as C-TIRADS 4 based on 2D-ultrasound combined with five contrast-enhanced ultrasound key frames.

Objectives: To apply machine learning to extract radiomics features from thyroid two-dimensional ultrasound (2D-US) combined with contrast-enhanced ultrasound (CEUS) images to classify and predict benign and malignant thyroid nodules, classified according to the Chinese version of the thyroid imaging reporting and data system (C-TIRADS) as category 4. Materials and methods: This retrospective study included 313 pathologically diagnosed thyroid nodules (203 malignant and 110 benign). Two 2D-US images and five CEUS key frames ("2nd second after the arrival time" frame, "time to peak" frame, "2nd second after peak" frame, "first-flash" frame, and "second-flash" frame) were selected to manually label the region of interest using the "Labelme" tool. A total of 7 images of each nodule and their annotates were imported into the Darwin Research Platform for radiomics analysis. The datasets were randomly split into training and test cohorts in a 9:1 ratio. Six classifiers, namely, support vector machine, logistic regression, decision tree, random forest (RF), gradient boosting decision tree and extreme gradient boosting, were used to construct and test the models. Performance was evaluated using a receiver operating characteristic curve analysis. The area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC), and F1-score were calculated. One junior radiologist and one senior radiologist reviewed the 2D-US image and CEUS videos of each nodule and made a diagnosis. We then compared their AUC and ACC with those of our best model. Results: The AUC of the diagnosis of US, CEUS and US combined CEUS by junior radiologist and senior radiologist were 0.755, 0.750, 0.784, 0.800, 0.873, 0.890, respectively. The RF classifier performed better than the other five, with an AUC of 1 for the training cohort and 0.94 (95% confidence interval 0.88-1) for the test cohort. The sensitivity, specificity, accuracy, PPV, NPV, and F1-score of the RF model in the test cohort were 0.82, 0.93, 0.90, 0.85, 0.92, and 0.84, respectively. The RF model with 2D-US combined with CEUS key frames achieved equivalent performance as the senior radiologist (AUC: 0.94 vs. 0.92, P = 0.798; ACC: 0.90 vs. 0.92) and outperformed the junior radiologist (AUC: 0.94 vs. 0.80, P = 0.039, ACC: 0.90 vs. 0.81) in the test cohort. Conclusions: Our model, based on 2D-US and CEUS key frames radiomics features, had good diagnostic efficacy for thyroid nodules, which are classified as C-TIRADS 4. It shows promising potential in assisting less experienced junior radiologists.

High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules.

PURPOSE: To explore the novel diagnostic value of epigenetic imprinting biomarkers in thyroid nodules. PATIENTS AND METHODS: A total of 550 patients with fine-needle aspiration (FNA)-evaluated and histopathologically confirmed thyroid nodules were consecutively recruited from eight medical centers. Quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) was used to assess the allelic expression of imprinted genes SNRPN and HM13, on the basis of which a diagnostic grading model for thyroid nodules was developed. The model was retrospectively trained on 124 postsurgical thyroid samples, optimized on 32 presurgical FNA samples, and prospectively validated on 394 presurgical FNA samples. Blinded central review-based cytopathologic and histopathologic diagnoses were used as the reference standard. RESULTS: For thyroid malignancy, the QCIGISH test achieved an overall diagnostic sensitivity of 100% (277/277), a specificity of 91.5% (107/117; 95% CI, 86.4 to 96.5), a positive predictive value (PPV) of 96.5% (95% CI, 94.4 to 98.6), and a negative predictive value (NPV) of 100% in the prospective validation, with a diagnostic accuracy of 97.5% (384/394; 95% CI, 95.9 to 99.0). QCIGISH demonstrated a PPV of 97.8% (95% CI, 94.7 to 100) and NPV of 100%, with a diagnostic accuracy of 98.2% (111/113; 95% CI, 95.8 to 100), for indeterminate Bethesda III-V thyroid nodules. QCIGISH demonstrated a PPV of 96.6% (95% CI, 91.9 to 100) and a NPV of 100%, with a diagnostic accuracy of 97.5% (79/81; 95% CI, 94.2 to 100), for Bethesda III-IV. For Bethesda VI, QCIGISH showed a 100% (184/184) accuracy. CONCLUSION: This imprinting biomarker-based test can effectively distinguish malignant from benign thyroid nodules. The high PPV and NPV make the test both an excellent rule-in and rule-out diagnostic tool. With such a diagnostic performance and its technical simplicity, this novel thyroid molecular test is clinically widely applicable.

Applying contrast-enhanced ultrasound model to distinguish atypical focal adenomyosis from uterine leiomyomas.

Background: Different from conventional ultrasound, contrast-enhanced ultrasound (CEUS) is better in observing microperfusion. For atypical focal adenomyosis and uterine leiomyomas that are difficult to be distinguished by conventional ultrasound, this study aims to further improve the differential diagnosis performance by using CEUS model. Methods: After screening the cases with difficulties in identifying focal myometrium lesions through conventional ultrasound, the number of cases covered in the focal adenomyosis group and leiomyomas group were 60 and 30 in derivation cohort, 14 and 7 in validation cohort. The qualitative and quantitative characteristics of CEUS were analyzed according to the surgical pathology. The qualitative characteristics include: the enhancement level based on the myometrium, the contrast enhancement pattern, the enhanced time of the lesion based on the myometrium, post-contrast lesion border, the distribution of the contrast agent, and the wash-out time based on the myometrium. The quantitative characteristics include: arrive time (AT), time to peak (TTP), peak intensity (PI), ΔAT, ΔTTP, ΔPI, |ΔAT|, |ΔTTP|, |ΔPI| and lesion temporal variability. Multiple logistic regression analysis was used to screen the independent risk factors, and a risk prediction model for the differential diagnosis of the two diseases was established. The area under the receiver operating characteristic (ROC) curve (AUC) was used to assess the diagnostic performance of the model. The validation cohort was used to further evaluate the diagnostic performance of the model. Results: Through the multivariate analysis, it concluded that short-term vessels first enhanced enhancement mode, unclear boundary, lesion temporal variability under CEUS >9.5 s, uneven contrast agent distribution could be independent risk factors for the diagnosis of adenomyosis [AUC =0.908, 95% confidence interval (CI): 0.833-0.982]. We also determined the sensitivity (98.33%), specificity (70.00%), positive predictive value (PPV) (86.76%), negative predictive value (NPV) (95.45%), and accuracy (87.78%) of this model. Based on pathological diagnosis, the sensitivity and specificity of the model in the validation cohort were both 85.71%, with NPV of 75% and PPV of 92.3%. The area under the ROC curve was 0.898 (95% CI: 0.742-1.000). Conclusions: The establishment of CEUS model has certain clinical application value in differentiating atypical focal adenomyosis from leiomyomas.

Differentiation of Thyroid Nodules (C-TIRADS 4) by Combining Contrast-Enhanced Ultrasound Diagnosis Model With Chinese Thyroid Imaging Reporting and Data System.

Objectives: To establish a contrast-enhanced ultrasound (CEUS) diagnostic schedule by CEUS analysis of thyroid nodules of C-TIRADS 4. To establish a CEUS-TIRADS diagnostic model to differentiate thyroid nodules (C-TIRADS 4) by combining CEUS with Chinese thyroid imaging reporting and data system (C-TIRADS). Methods: A total of 228 thyroid nodules (C-TIRADS 4) were estimated by CEUS. The arrival time, enhancement degree, enhancement homogeneity, enhancement pattern, enhancement ring, and wash-out time were analyzed in CEUS for all of the nodules. Multivariate factors logistic analysis was performed and a CEUS diagnostic schedule was established. If the nodule had a regular hyper-enhancement ring or got a score of less than 2 in CEUS analysis, CEUS-TIRADS subtracted 1 category. If the nodule got a score of 2 in the CEUS schedule, the CEUS-TIRADS category remained the same as before. If the nodule got a score of more than 2 in the CEUS schedule, CEUS-TIRADS added 1 category. When it reflected an absent enhancement in CEUS, the nodule was judged as CEUS-TIRADS 3. All of the C-TIRADS 4 nodules were re-graded by CEUS-TIRADS. We then compare the diagnosis performance of C-TIRADS, CEUS, and CEUS-TIRADS by sensitivity, specificity, and accuracy. Results: Among the 228 C-TIRADS 4 nodules, 69 were determined as C-TIRADS 4a, 114 were C-TIRADS 4b, and 45 were C-TIRADS 4c. The sensitivity, specificity, and accuracy of C-TIRADS were 93.1%, 55.3%, and 74.6% respectively. The area under the curve was 0.753. Later arrival time, hypo-enhancement, heterogeneous enhancement, centripetal enhancement, and rapid washout were risk factors of malignancy in multivariate analysis. The sensitivity, specificity, and accuracy of CEUS were 78.7%, 87.5%, and 83.3% respectively. The area under the curve was 0.803. By CEUS-TIRADS diagnostic model combining CEUS with C-TIRADS, a total of 127 cases were determined as malignancy (111 were malignant and 16 were benign) and 101 were diagnosed as benign ones (5 were malignant and 96 were benign). The sensitivity, specificity, and accuracy of CEUS-TIRADS were 95.7%, 85.7%, and 92.1% respectively. The area under the curve was 0.916. The diagnostic performance of CEUS-TIRADS was significantly better than CEUS and C-TIRADS. The difference was statistically significant (P<0.05). Conclusions: The diagnostic schedule of CEUS could get better diagnostic performance than US in the differentiation of thyroid nodules. The CEUS-TIRADS combining CEUS analysis with C-TIRADS could make up for the deficient sensibility of C-TIRADS, showing a better diagnostic performance than US and CEUS.

Systematic Analysis of the Expression Profile and Prognostic Significance of the IGF2BP Family in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD), the most common type of lung cancer associated with poor prognosis, has become a major health problem. IGF2BPs are types of N6-methyladenosine reader proteins, comprising IGF2BP1, IGF2BP2, and IGF2BP3, that promote LUAD progression. However, the expression profiles and prognostic value of IGF2BPs in LUAD remain unclear. OBJECTIVE: This study aimed to analyze the expression profiles and prognostic significance of the IGF2BP family in lung adenocarcinoma. METHODS: In this study, we included tissue data of LUAD patients and normal or para-carcinoma from the TCGA database and the GTEx project. Using survival analysis, Kaplan-Meier curves, and Cox proportional hazards model, we analyzed the expression profiles and prognostic significance of the IGF2BP family. RESULTS: Patients with high expression levels of IGF2BPs showed a significant association with poor overall survival (p < 0.05). Moreover, the somatic mutation rates of IGF2BP1, IGF2BP2, and IGF2BP3 were determined as 2.65, 1.59, and 1.76%, respectively, by investigating the genetic mutation. In addition, there were significant associations between TMB and IGF2BP family expression profiles, which positively correlated with the expression of PD-1 (p < 0.05). Cox proportional hazard model for LUAD showed the risk score for IGF2BP1, p-TNM stage, and so forth, all independent prognostic indicators for LUAD patients. Finally, the co-expression genes were obtained to build a PPI network and analyze the hub genes of the IGF2BP family. CONCLUSION: Our study provides further insights into the role of the IGF2BP family in LUAD and identifies 10 genes that may be associated with IGF2BPs in LUAD patients.

FOXK2 promotes the proliferation of papillary thyroid cancer cell by down-regulating autophagy.

Papillary thyroid cancer (PTC) is the most common endocrine system tumor. FOXK2 is involved in the development of different types of cancers, however, its function has not been investigated in papillary thyroid cancer. In the present study, we demonstrated that FOXK2 expression was up-regulated in papillary thyroid carcinoma tissues compared with matched normal tissues. Importantly, we found that FOXK2 expression was significantly associated with the tumor size, T stage, and TNM stage. Furthermore, stable knockdown of FOXK2 markedly inhibited PTC cell proliferation, significantly increased the ratio of LC3-II/LC3-I, and reduced p62 expression, whereas overexpression of FOXK2 showed opposite effects. In FOXK2 knockdown cell lines, mCherry-GFP-LC3 immunofluorescence demonstrated increased punctate aggregates of mCherry-GFP-LC3, and transmission electron microscopy revealed increased numbers of autophagosomes. Autophagy-related protein ULK1, VPS34, and FOXO3 were markedly up-regulated by FOXK2 knockdown and down-regulated by FOXK2 overexpression. Finally, autophagy inhibitor 3-MA attenuated autophagy activation and rescued the inhibition of cell proliferation caused by FOXK2 knockdown, suggesting that FOXK2 silencing inhibits cell proliferation through up-regulating autophagy. These findings revealed an important role of FOXK2 in PTC progression and suggested that FOXK2 might be a potential new target for the diagnosis and treatment of PTC.

Erratum: FOXK2 promotes the proliferation of papillary thyroid cancer cell by down-regulating autophagy: Erratum.

[This corrects the article DOI: 10.7150/jca.60730.].

Acute thyroid swelling after fine needle aspiration-a case report of a rare complication and a systematic review.

BACKGROUND: Thyroid fine needle aspiration (FNA) is the procedure of choice in the management of thyroid nodules. Acute thyroid swelling after FNA is a rare complication and is reported in a finite number of literatures. To the best of our knowledge, only seven reported cases exist in literatures. This study describes an addition case with an acute thyroid swelling after FNA, as well as puts forward a new hypothesis of this phenomenon. CASE PRESENTATION: The case is presented of a 30-year-old female with an acute thyroid swelling after FNA, with funicular hypoechoic lesions in thyroid gland. The size of thyroid was 1.5-fold enlarged in the unilateral thyroid gland. No complains of pain or other discomforts with her and no signs of hemorrhage were found along the passage of the fine needle. The episode was recovered spontaneously. CONCLUSIONS: An acute thyroid swelling is a rare complication of FNA. A hypothesis of anaphylactic reaction was suggested in our study. Physicians should pay more attention of this phenomenon and more information is needed to support our hypothesis.

"Double-Flash": An Innovative Method to Diagnose Papillary Thyroid Microcarcinomas.

The aim of the study was to investigate the diagnostic ability of an innovative method called "Double-Flash" during contrast-enhanced ultrasound (CEUS) examination in papillary thyroid microcarcinomas. A total of 43 nodules measuring <10 mm and with definite pathology confirmed by surgery or fine-needle aspiration biopsy (FNAB) were included in this study. The bottom of "Flash" was pressed in the 40th and 60th seconds, respectively, defined as "Double-Flash." The curve of reperfusion was evaluated and the diagnostic value of "Double-Flash" was compared with that of CEUS. Pathologic results obtained by surgery or FNAB revealed there were 27 malignant and 16 benign nodules. The sensitivity, specificity and accuracy of CEUS were 70.0%, 53.8% and 65.1%. With "Double-Flash," the sensitivity, specificity and accuracy were 92.3%, 82.3% and 88.4%, respectively. The difference was statistically significant. Higher diagnostic ability is obtained with "Double-Flash." The parameter based on the new method could improve the diagnostic performance of quantitative diagnosis in CEUS. The change in the perfusion curve after "Flash" may be a strong indicator of malignancy.