Tolvaptan therapy for edema in patients with chronic kidney disease.

OBJECTIVE: Tolvaptan is a vasopressin V2 receptor antagonist that is commonly prescribed to alleviate edema associated with renal diseases. However, the clinical benefits of tolvaptan in chronic kidney disease (CKD) remain unclear. This study aimed to evaluate the effectiveness of tolvaptan in managing edema caused by CKD. MATERIALS AND METHODS: The efficacy and treatment regimen of tolvaptan were assessed in a cohort of 96 patients with renal edema and CKD. During the treatment, the patients' creatinine (CR), uric acid (UA), and estimated glomerular filtration rate (eGFR) were monitored as important indicators of kidney function. Coagulation-associated molecules including fibrinogen, D-dimer, and fibrin degradation products (FDPs) were measured. Electrolyte disorders and acute kidney injury were closely monitored. Tolvaptan was administered at a daily dose of 7.5 mg, and 30 mg of edoxaban was administered to manage deep vein thrombosis. RESULTS: During the course of tolvaptan therapy, the eGFR of the patients was not declined. Edema was eliminated in 82.18% of patients. Proteinuria was reduced in the patients (p < 0.05). There were no significant changes in serum sodium levels throughout treatment, and no significant difference was observed in blood volume between the end of treatment and baseline levels. Importantly, acute kidney injury did not occur, and renal edema and deep vein thrombosis were successfully treated. CONCLUSION: As long as a rational treatment regimen is followed, tolvaptan is a safe and effective diuretic for treating edema in CKD, even in the late stages of CKD without reducing residual renal function in the patients.

Publications on ultrasound-guided thermal ablation for thyroid nodules from 2000 to 2022: a bibliometric analysis.

BACKGROUND: Thyroid nodules are increasingly treated with minimally invasive surgery. Thermal ablation could efficiently treat patients with benign thyroid nodules, recurrent thyroid cancer, and low-risk papillary thyroid carcinoma. This research aims to explore the research field of thermal ablation for thyroid nodules using bibliometric analysis. METHODS: The web of science core collection (WoSCC) database was utilized from its inception to 1 October 2022, to collect research articles and reviews on ultrasound-guided thermal ablation for thyroid nodules. We applied the R package 'bibliometrix' to summarize the main findings, calculate the occurrences of the top keywords and visualize the international collaboration networks. The co-authorship and co-occurrence analyses were conducted with VOSviewer software. CiteSpace was used to identify the top references and keywords with the highest citation bursts. RESULTS: A total of 820 publications from 32 countries were retrieved. The annual number of related publications showed an increasing trend. China, Italy, and Korea were the most contributing countries. The University of Ulsan College of Medicine in Korea was the most productive institution, and Jung Hwan Baek published the maximum number of articles. The International Journal of Hyperthermia was the most productive journal. 'Papillary thyroid micro-carcinoma (PTMC)' and 'association guideline' were the most frequently used keywords in the field of thermal ablation for thyroid nodules, which indicated the potential hot research topics and frontiers in the future. CONCLUSION: This bibliometric study conducts a comprehensive analysis of publications on thermal ablation for thyroid nodules, which aids investigators in discovering potential research directions.

[Influencing Factors of Bethesda â ¢ Results in Fine-Needle Aspiration Biopsy of Thyroid Nodules].

Objective To investigate the influencing factors of Bethesda Ⅲ results in fine-needle aspiration biopsy of thyroid nodules.Methods A total of 300 thyroid nodules with cytological diagnosis results were analyzed retrospectively,including 100 Bethesda Ⅲ nodules and 50 nodules of Bethesda Ⅱ,Ⅳ,Ⅴ,and Ⅵ categories,respectively.Univariate analysis and Logistic regression analysis were performed on the clinical data of patients and the ultrasound signs of thyroid nodules to clarify the factors influencing the diagnosis of Bethesda Ⅲ nodules.Results Univariate analysis showed that Bethesda Ⅲ nodules were mostly adjacent to the capsule(P<0.001),with no blood flow in the color Doppler assessment(P=0.011)and lack of blood supply(P=0.033)and maximum diameter ≤0.9 cm(P=0.038)as revealed by the contrast-enhanced ultrasound.Logistic regression showed that the position close to the capsule(OR=5.110,95%CI=2.153-12.130,P<0.001)and color Doppler without blood flow signal(OR=3.015,95%CI=1.094-8.311,P=0.033)were independent risk factors for the diagnosis of Bethesda Ⅲ nodules.Conclusions The puncture difficulty caused by the dangerous position of thyroid nodules close to the capsule and the aspiration difficulty caused by the absence of blood flow signal in color Doppler are the main factors influencing the diagnosis of Bethesda Ⅲ nodules.Therefore,corresponding avoidance measures should be taken during the aspiration process to reduce the diagnosis results of Bethesda Ⅲ nodules.

[Nomogram-Based Prediction of Risk of Cervical Lymph Node Metastasis in Differentiated Thyroid Carcinoma].

Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group (n=444) and a validation group (n=125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P<0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95%CI=0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

[Evaluation of Extrathyroidal Extension of Papillary Thyroid Microcarcinoma With Three-Dimensional Tomographic Ultrasound Imaging].

Objective To evaluate extrathyroidal extension (ETE) in papillary thyroid microcarcinoma (PTMC) with three-dimensional tomographic ultrasound imaging (3D-TUI). Methods A total of 97 thyroid nodules of 79 patients with PTMC treated in PUMC Hospital from February 2016 to January 2018 were included in this study.Two ultrasound experts performed independent blinded assessment of the relationship between thyroid nodules and thyroid capsule by two-dimensional ultrasound (2D-US) and 3D-TUI.The results of 2D-US and 3D-TUI in evaluating ETE were compared with intraoperative findings and postoperative histological and pathological results. Results Among the 97 nodules,54 (55.7%) nodules had ETE.The diagnostic sensitivity (68.5% vs.37.0%;χ2=10.737,P=0.002),accuracy (74.5% vs.56.7%;χ2=6.686,P=0.015),and area under the receiver operating characteristic curve[0.761 (95%CI=0.677-0.845) vs.0.592 (95%CI=0.504-0.680);Z=3.500,P<0.001] of 3D-TUI were higher than those of 2D-US.However,3D-TUI and 2D-US showed no significant difference in the specificity (84.1% vs.81.4%;χ2=0.081,P=0.776),negative predictive value (67.9% vs.50.7%;χ2=3.645,P=0.066),or positive predictive value (84.1% vs.71.4%;χ2=1.663,P=0.240). Conclusion Compared with 2D-US,3D-TUI demonstrates increased diagnostic efficiency for ETE of PTMC.

[Influencing Factors and Prediction Model of Performance of Needle Visualization in Fine Needle Aspiration of Thyroid Nodules].

Objective To investigate the influencing factors and establish a model predicting the performance of needle visualization in fine-needle aspiration (FNA) of thyroid nodules. Methods This study prospectively included 175 patients who underwent FNA of thyroid nodules in the Department of Ultrasound in China-Japan Friendship Hospital and compared the display of the needle tips in the examination of 199 thyroid nodules before and after the application of needle visualization.We recorded the location,the positional relationship with thyroid capsule,ultrasonic characteristics,and the distribution of the soft tissue strip structure at the puncture site of the nodules with unclear needle tips display before using needle visualization.Furthermore,according to the thyroid imaging reporting and data system proposed by the American College of Radiology,we graded the risk of the nodules.Lasso-Logistic regression was employed to screen out the factors influencing the performance of needle visualization and establish a nomogram for prediction. Results The needle tips were not clearly displayed in the examination of 135 (67.8%) and 53 (26.6%) nodules before and after the application of needle visualization,respectively,which showed a significant difference (P<0.001).Based on the positional relationship between the nodule and capsule,anteroposterior/transverse diameter (A/T) ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site,a nomogram was established to predict the probability of unclear display of the needle tips after application of needle visualization.The C-index of the prediction model was 0.75 (95%CI=0.67-0.84) and the area under the receiver operating characteristic curve was 0.72.The calibration curve confirmed the appreciable reliability of the prediction model,with the C-index of 0.70 in internal validation. Conclusions Needle visualization can improve the display of the needle tip in ultrasound-guided FNA of thyroid nodules.The nomogram established based on ultrasound features such as the positional relationship between the nodule and capsule,A/T ratio,blood supply,and the distribution of subcutaneous strip structure at the puncture site can predict whether needle visualization is suitable for the examination of nodules.

A novel prognostic model based on log odds of positive lymph nodes to predict outcomes of patients with anaplastic thyroid carcinoma after surgery.

OBJECTIVE: The eighth version of the American Joint Committee on Cancer (8th AJCC) system for anaplastic thyroid carcinoma (ATC) added lymph node (LN) metastasis as the staging element. This study aimed to explore the association between LN status and ATC's prognosis, identify the optimal LN index and establish a novel prognostic model. DESIGN AND PATIENTS: Data of 199 ATC patients after surgery were collected from the Surveillance, Epidemiology and End Results (SEER) database, then randomly divided into training and validation cohorts. MEASUREMENTS: We compared the prognostic value of AJCC N status, number of positive LN (PLNN), ratio of LN (LNR) and log odds of positive LN (LODDS). We conducted univariate and multivariate Cox analyses to determine the independent prognostic factors for ATC, and constructed a novel prognostic model. The concordance index (C-index), area under the receiver-operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA) were used to assess the nomogram's predictive performance. RESULTS: LODDS showed the highest accuracy among four LN systems to predict overall survival (OS) for ATC. In the training cohort, the C-index of the LODDS-based nomogram was 0.738. The AUCs were 0.813, 0.850 and 0.869 for predicting 1-, 2- and 3-year OS, respectively. The calibration plots and DCA indicated the great clinical applicability of the model. The above results were verified in the validation cohort. CONCLUSIONS: LODDS showed better predictive performance than other LN schemes in ATC. The LODDS-incorporated nomogram has the potential to more precisely predict the prognosis for ATC patients than the AJCC system.

Construction and Validation of a Nomogram Based on the Log Odds of Positive Lymph Nodes to Predict the Prognosis of Medullary Thyroid Carcinoma After Surgery.

BACKGROUND: This study aimed to explore the prognostic impact that the log odds of positive lymph nodes (LODDS) has on medullary thyroid cancer (MTC) and to develop a nomogram incorporating LODDS to predict the cancer-specific survival (CSS) of MTC. METHODS: Data from 1110 MTC patients after total thyroidectomy were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into training and validation cohorts. The prognostic efficiency of N status from the American Joint Committee on Cancer (AJCC) staging system, the number of positive lymph nodes (PLNN), and LODDS were compared using the Harrell concordance index (C-index), the Akaike information criterion (AIC), and area under the receiver operating characteristic (ROC) curve (AUC). A multivariate Cox analysis was performed to determine the independent prognostic factors, and a nomogram based on LODDS was constructed. The nomogram's performance was assessed with the C-index, AUC, calibration curves, and decision curve analysis (DCA). RESULTS: Among the three lymph node (LN) staging systems, LODDS showed the highest accuracy in predicting CSS for MTC. In the training cohort, the C-index of the LODDS-based nomogram was 0.895. The AUCs were 0.949, 0.917, 0.925, and 0.901 for predicting 1-, 3-, 5- and 10-year CSS, respectively. The calibration plots and DCA showed the superior clinical applicability of the nomogram. These results were verified in the validation cohort. CONCLUSIONS: As an independent prognostic factor for MTC, LODDS demonstrated superior prognostic efficiency over N status and PLNN. This LODDS-based nomogram yielded better performance than the AJCC tumor-node-metastasis (TNM) staging system in predicting CSS after surgery for MTC.

Comparison of Ultrasound Features of Primary Metastatic Papillary Thyroid Carcinoma and Recurrent/Persistent Metastatic Cervical Lymph Nodes.

Objective To explore the ultrasound features and levels of cervical lymph node metastases in primary and recurrent/persistent papillary thyroid cancer (PTC).Methods We retrospectively analyzed the clinical data of 2181 patients who underwent cervical lymph nodes dissection for PTC from January 1st 2015 to January 1st 2016.Totally 418 PTC patients (with 622 lymph nodes) who met the inclusion criteria entered the final analysis.Patients who had not received any prior thyroid treatment (surgery with or without radioactive iodine) were categorized as the primary group (352 patients with 527 metastatic lymph nodes),and patients who had received prior treatment (thyroidectomy with or without radioactive iodine) for PTC were categorized as recurrent/persistent group (66 patients with 95 metastatic lymph nodes).Pathological results from lymph node dissections were used as the gold standards by means of level-to-level analysis.Results The mean of the minimum axis diameter of the lymph nodes in the primary group was (6.7±3.6)mm,and that of the recurrent/persistent group was (6.6±3.1)mm (U=0.180,P=0.857).The proportion of metastasis in the central area of primary group was 40.0%,which was significantly higher than that in the recurrent/persistent group (12.6%);the proportion of metastasis in the lateral area was 60.6% in the primary group,which was significantly lower than that in the recurrent/persistent group (87.4%)(χ2=26.288,P<0.001).In lateral metastatic lymph nodes,Ⅲ level was the most common place in both groups.Level Ⅴ metastatic lymph was rare in both primary group and recurrent/persistent group.Calcifications (63.1% vs. 48.2%;χ2=7.207,P=0.007) and peripheral vascularity (81.1% vs. 59.4%;χ2= 16.147, P<0.001) were more common in the recurrent/persistent group.The round shape,absence of an echogenic hilum,hyperechogenicity,and cystic aspects were not significantly different between these two groups (all P>0.05).Conclusions Primary metastatic lymph nodes often occur in the central area of lymph nodes,while lateral metastatic lymph nodes are more common in recurrent/persistent PTC.For metastatic lymph nodes,calcifications and peripheral vascularity are more common in recurrent/persistent PTC.

Prolonged heterogeneous liver enhancement accompanied by abdominal symptoms after sonographic contrast agent injection: a cross-sectional study.

Background: To report the occurrence of abdominal symptoms in patients who presented with prolonged heterogeneous liver enhancement (PHLE) after injecting contrast agent SonoVue®. Methods: A total of 105 patients who indicated to have contrast-enhanced ultrasound (CEUS) examinations were consecutively observed. The liver scanning under ultrasound was performed before and after the contrast agent injection. Patients' basic information, clinical manifestations, and ultrasound images under B-mode and CEUS mode were respectively recorded. For patients exhibiting abdominal symptoms, the occurrence and last time of symptoms were recorded in detail. We subsequently compared the difference in clinical characteristics between patients with and without the PHLE phenomenon. Results: In 20 patients with the PHLE phenomenon, 13 showed abdominal symptoms. Eight patients (61.5%) appeared to have mild defecation sensation, and 5 (38.5%) showed apparent abdominal pain. The PHLE phenomenon began to appear within 15 minutes to 1.5 hours after the intravenous injection of SonoVue®. This phenomenon lasted for 30 minutes to 5 hours in ultrasound. Patients with severe abdominal symptoms showed large-area and diffuse PHLE patterns. Only sparse hyperechoic spots in the liver were detected in patients with mild discomfort. Abdominal discomfort resolved spontaneously in all patients. Meanwhile, the PHLE gradually disappeared without any medical treatment. In the PHLE-positive group, the proportion of patients with a history of gastrointestinal disease was significantly higher (P=0.02). Conclusions: Patients with the PHLE phenomenon can exhibit abdominal symptoms. We suggest gastrointestinal disorders may contribute to PHLE, which can be considered a harmless phenomenon that does not affect the safety profile of SonoVue®.

Real-life utility of five-gene panel test in preoperative thyroid fine-needle aspiration biopsy: a large cohort of 740 patients study.

PURPOSE: Fine-needle aspiration (FNA) biopsy is an effective method to discriminate malignant thyroid nodules but reaches indeterminate results in approximately 30% of cases. Molecular testing can improve the diagnostic accuracy of FNA. This study aimed to investigate the real-life utility of the five-gene panel testing in thyroid FNAs. METHODS: 759 thyroid nodules from 740 patients under FNAs were retrospectively enrolled. Gene mutation information and clinical parameters, including age, gender, tumor size, and lymph node metastasis, were respectively recorded. Cytological results were classified based on The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We analyzed mutational hotspots in BRAF, KRAS, NRAS, HRAS, and TERT genes from FNA specimens. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated to assess diagnostic performance. RESULTS: We identified 549 five-gene mutations in 759 nodules (72.3%), and the mutation frequency increased from the lower TBSRTC category to the upper category. BRAF.p.V600E showed the highest mutation incidence (71.3%) in the five-gene panel, correlated with the small to medium diameter (p = 0.008, p = 0.012) and high cytological categories (p < 0.001). The sensitivity, specificity, PPV, NPV, and accuracy of the combination of FNA cytology and five-gene detection were 96.83%, 100%, 100%, 42.86%, and 96.90%, respectively. CONCLUSIONS: The mutation frequency of the five-gene panel is 72.3% in thyroid FNAs. BRAF.p.V600E has the highest alteration rate, which is closely associated with tumor size and cytological results. The five-gene panel can improve the sensitivity and accuracy of FNA cytology, which may represent a valid adjunct technique in distinguishing thyroid nodules.

Contrast-enhanced ultrasound combined targeted microbubbles for diagnosis of highly aggressive papillary thyroid carcinoma.

Background: Accurate diagnosis of highly aggressive papillary thyroid cancer (PTC) may greatly help avoid overdiagnosis and overtreatment of PTC. However, there is still a lack of a convenient and accurate method. Targeted microbubbles, an emerging ultrasound contrast agent, have the potential to accurately diagnose highly aggressive PTC. Purpose: To design and prepare a targeted microbubble for specific contrast-enhanced ultrasound (CEUS) imaging of highly invasive PTC. Methods: Using ß-galactoside-binding protein galectin-3 (Gal-3) overexpressed on the surface of highly invasive PTC cells as a target, C12 polypeptide (ANTPCGPYTHDCPVKR) with high affinity and specificity for Gal-3 was coupled to the surface of lipid microbubbles to prepare targeted microbubbles (Gal-3-C12@lipo MBs). The targeted microbubbles were prepared by thin-film hydration method and mechanical shaking method. The morphology, diameter, concentration and stability of microbubbles were investigated by fluorescence microscopy and an AccuSizer. The biosafety of microbubbles was studied using BCPAP cells through CCK8 assay. Confocal laser scanning microscope and flow cytometry were applied to research the cellular uptake of microbubbles to investigate the targeting ability to highly aggressive PTC. Finally, the specific contrast-enhanced ultrasound imaging of microbubbles in highly invasive PTC was validated on the mice bearing subcutaneous BCPAP tumor model via a clinically ultrasound imaging system. Results: Gal-3-C12@lipo MBs were successfully prepared which showed a well-defined spherical morphology with an average diameter of 1.598 ± 0.848 µm. Gal-3-C12@lipo MBs showed good stability without rupture within 4 hours after preparation. At the cellular level, Gal-3-C12@lipo MBs exhibited favorable biosafety and superior targeting ability to BCPAP cells, with 2.8-fold higher cellular uptake than non-targeted lipid microbubbles (Lipo MBs). At the animal level, Gal-3-C12@lipo MBs significantly improved the quality of contrast-enhanced ultrasound imaging in highly invasive PTC, with an echo intensity of tumor significantly higher than that of Lipo MBs. Conclusion: We designed and fabricated a novel targeted microbubble for the specific ultrasound imaging diagnosis of highly aggressive PTC. The targeted microbubbles have good stability, superior biosafety and high targeting specificity, which can significantly improve the tumor signal-to-noise ratio of highly invasive PTC, and have the potential to facilitate and accurately diagnose highly invasive PTC.

The analysis and validation of the prediction value of conventional and contrast-enhanced ultrasonography for BRAF mutant papillary thyroid microcarcinoma.

Background: BRAF has certain potential in distinguishing aggressive papillary thyroid microcarcinoma (PTMC). However, it is not recommended to conduct BRAF analysis for all suspicious thyroid nodules <1 cm. In order to investigate the ultrasound value indicating BRAF mutation among PTMC, which showed discrepancy in previous studies, we aimed to establish a predictive model based on conventional and contrast-enhanced ultrasonography. Methods: We consecutively and retrospectively enrolled patients with PTMC who underwent fine-needle aspiration biopsy (FNAB) at our hospital between January 2020 and January 2021. All PTMC patients received conventional and contrast-enhanced ultrasound prior to FNAB, samples gained went through cytological analysis and BRAF testing subsequently. The following conventional ultrasonography data were analyzed: maximum diameter, echogenicity, echo homogeneity, echogenic foci, location, shape, boundary, aspect ratio, and blood flow volume. Moreover, the following contrast-enhanced ultrasonography data were also analyzed: degree, homogeneity, completeness, and enhancement method. Time-intensity curves from contrast-enhanced ultrasonography were analyzed using VueBox software for different regions of interest, including the entire tumor, the area of strongest enhancement, and healthy thyroid glands. The independent risk factors for BRAF mutation in PTMC were identified using univariate and multivariate logistic regression. Their predictive value was tested through internal validation. Results: Of the 103 PTMC lesions analyzed, 72 involved BRAF mutations. Five independent ultrasonographic risk factors for BRAF mutation were identified: relative time to peak value in the area of strongest enhancement, unclear boundary, location adjacent to thyroid capsules, maximum diameter >0.5 cm, and punctate echogenic foci. A predictive model based on these factors was able to diagnose BRAF mutations in PTMC, with an area under the curve (AUC) of 0.824. During internal validation, this model showed an AUC of 0.723. Conclusions: Conventional and contrast-enhanced ultrasound characteristics, including relative time to peak value in the area of strongest enhancement, unclear boundary, location adjacent to thyroid capsules, maximum diameter >0.5 cm, and punctate echogenic foci, may be useful for predicting BRAF mutations in patients with PTMC.

Nomogram based on radiomics analysis of ultrasound images can improve preoperative BRAF mutation diagnosis for papillary thyroid microcarcinoma.

Background: The preoperative identification of BRAF mutation could assist to make appropriate treatment strategies for patients with papillary thyroid microcarcinoma (PTMC). This study aimed to establish an ultrasound (US) radiomics nomogram for the assessment of BRAF status. Methods: A total of 328 PTMC patients at the China-Japan Friendship Hospital between February 2019 and November 2021 were enrolled in this study. They were randomly divided into training (n = 232) and validation (n = 96) cohorts. Radiomics features were extracted from the US images. The least absolute shrinkage and selection operator (LASSO) regression was applied to select the BRAF status-related features and calculate the radiomics score (Rad-score). Univariate and multivariate logistic regression analyses were subsequently performed to identify the independent factors among Rad-score and conventional US features. The US radiomics nomogram was established and its predictive performance was evaluated via discrimination, calibration, and clinical usefulness in the training and validation sets. Results: Multivariate analysis indicated that the Rad-score, composition, and aspect ratio were independent predictive factors of BRAF status. The US radiomics nomogram which incorporated the three variables showed good calibration. The discrimination of the US radiomics nomogram showed better discriminative ability than the conventional US model both in the training set (AUC 0.685 vs. 0.592) and validation set (AUC 0.651 vs. 0.622). Decision curve analysis indicated the superior clinical applicability of the nomogram compared to the conventional US model. Conclusions: The US radiomics nomogram displayed better performance than the conventional US model in predicting BRAF mutation in patients with PTMC.

Development and validation of a nomogram based on stromal score to predict progression-free survival of patients with papillary thyroid carcinoma.

BACKGROUND: Growing evidence has proved that stromal cells, as the critical component of tumor microenvironment (TME), are closely associated with tumor's progression. However, the model based on stromal score to predict progression-free survival (PFS) in papillary thyroid carcinoma (PTC) has not been developed. The study aimed at exploring the relation between stromal score and prognosis, then establishing a nomogram to predict PFS of patients with PTC. METHOD: We obtained the stromal score and clinicopathological characteristics of PTC patients from The Cancer Genome Atlas (TCGA) database. Cox regression analysis assisted in selecting prognosis-related factors. A stromal score-based nomogram was built and verified in the training and validation cohorts, respectively. The calibration curve, concordance index (C-index), decision curve analysis (DCA) as well as receiver operating characteristic (ROC) curve assisted in measuring the performance exhibited by the nomogram. RESULTS: We divided 381 PTC patients into the training cohort (n = 269) and the validation cohort (n = 112) randomly. Compared with patients who had a low stromal score, patients with a high stromal score appeared with significantly better PFS [Hazard ratio (HR) and 95% confidence interval (CI): 0.294, 0.130-0.664]. The C-index of the PFS nomogram was 0.764 (0.662-0.866) in the training cohort and 0.717 (0.603-0.831) in the validation cohort. The calibration curves for PFS prediction in the nomogram were remarkably consistent with the actual observation. DCA indicated superior performance of the nomogram to predict PFS than the American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) staging system. The ROC curves showed the favorable sensitivity and specificity of the novel nomogram. CONCLUSION: High stromal score was significantly associated with improved PFS in patients with PTC. The nomogram based on the stromal score and clinicopathological patterns yielded a reliable performance to predict the prognosis of PTC.

Establishment of an Ultrasound Malignancy Risk Stratification Model for Thyroid Nodules Larger Than 4 cm.

BACKGROUND: The incidence and mortality of thyroid cancer, including thyroid nodules > 4 cm, have been increasing in recent years. The current evaluation methods are based mostly on studies of patients with thyroid nodules < 4 cm. The aim of the current study was to establish a risk stratification model to predict risk of malignancy in thyroid nodules > 4 cm. METHODS: A total of 279 thyroid nodules > 4 cm in 267 patients were retrospectively analyzed. Nodules were randomly assigned to a training dataset (n = 140) and a validation dataset (n = 139). Multivariable logistic regression analysis was applied to establish a nomogram. The risk stratification of thyroid nodules > 4 cm was established according to the nomogram. The diagnostic performance of the model was evaluated and compared with the American College Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), Kwak TI-RADS and 2015 ATA guidelines using the area under the receiver operating characteristic curve (AUC). RESULTS: The analysis included 279 nodules (267 patients, 50.6 ± 13.2 years): 229 were benign and 50 were malignant. Multivariate regression revealed microcalcification, solid mass, ill-defined border and hypoechogenicity as independent risk factors. Based on the four factors, a risk stratified clinical model was developed for evaluating nodules > 4 cm, which includes three categories: high risk (risk value = 0.8-0.9, with more than 3 factors), intermediate risk (risk value = 0.3-0.7, with 2 factors or microcalcification) and low risk (risk value = 0.1-0.2, with 1 factor except microcalcification). In the validation dataset, the malignancy rate of thyroid nodules > 4 cm that were classified as high risk was 88.9%; as intermediate risk, 35.7%; and as low risk, 6.9%. The new model showed greater AUC than ACR TI-RADS (0.897 vs. 0.855, p = 0.040), but similar sensitivity (61.9% vs. 57.1%, p = 0.480) and specificity (91.5% vs. 93.2%, p = 0.680). CONCLUSION: Microcalcification, solid mass, ill-defined border and hypoechogenicity on ultrasound may be signs of malignancy in thyroid nodules > 4 cm. A risk stratification model for nodules > 4 cm may show better diagnostic performance than ACR TI-RADS, which may lead to better preoperative decision-making.

The Number of Central Lymph Nodes on Preoperative Ultrasound Predicts Central Neck Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Prospective Cohort Study.

To evaluate the effectiveness of the number of central compartment lymph nodes (CLNs) on ultrasound (US) in predicting CLN metastasis (CLNM). We prospectively studied 309 papillary thyroid cancer (PTC) patients who underwent thyroidectomy with CLN dissection at our center from May 2017 to July 2017. The number and features of CLNs were evaluated preoperatively via US. All US examinations were performed using a Philips iU 22 or a GE Logiq 9 machine. Correlations between CLNs observed via preoperative US and amount of CLNM were evaluated. We found that ≥2 CLNs on the preoperative US was associated with CLNM (P < 0.01). For this feature, the sensitivity, specificity, and area under the curve (AUC) were 54.3%, 66.1%, and 0.61, respectively. The presence of both suspected metastasis and ≥2 CLNs on US had a specificity of 86.5%. In addition, ≥3 CLNs on preoperative US was associated with large-volume CLNM (>5 metastatic CLNs) (P < 0.01). For this feature, the sensitivity, specificity and AUC were 54.8%, 74.5% and 0.65, respectively. The presence of both suspected metastasis and ≥3 CLNs on US had a specificity of 84.9%. The presence of suspected metastasis and/or ≥3 CLNs had a sensitivity of 80.6%. Our results suggest that ≥2 and ≥ 3 CLNs on preoperative US may serve as ancillary preoperative markers for predicting CLNM.

Blood-Rich Enhancement in Ultrasonography Predicts Worse Prognosis in Patients With Papillary Thyroid Cancer.

Contrast-enhanced ultrasound (CEUS) can be used to evaluate microcirculation in cancers, which in turn is associated with the biologic features and ultimately patient prognosis. We conducted a retrospective analysis to examine potential association between CEUS parameters and prognosis in patients with papillary thyroid cancer (PTC). The analysis included 306 patients who underwent CEUS prior to thyroidectomy at our center during a period from 2012 to 2019. Subjects with excellent response (ER) were compared to the non-ER group (including indeterminate response, biochemical incomplete response and structural incomplete response). During the median follow-up of 34 months, ER was observed in 195 (63.7%) subjects. The remaining 111 (36.3%) patients developed non-ER events, with distant metastasis in five (1.6%) cases. In a multivariate COX regression, non-ER event was associated with the male sex (OR = 1.83, 95%CI: 1.21-2.76) and blood-rich enhancement in CEUS (OR = 1.69, 95%CI: 1.04-2.75). Based on this finding, we developed a predictive model: high risk for developing non-ER events was defined as having both risk factors; low risk was defined as having none or only one risk. In receiver operating characteristic (ROC) analysis, the area under the curve was 0.59 (95%CI: 0.52-0.66). The sensitivity and specificity were 17.1 and 95.4%, respectively. The positive and negative predictive values were 67.9 and 66.9%, respectively. In conclusion, blood-rich enhancement in CEUS is associated with non-ER events after thyroidectomy in patients with PTC.

Differentiation of Thyroid Nodules Difficult to Diagnose With Contrast-Enhanced Ultrasonography and Real-Time Elastography.

According to the 2015 American Thyroid Association (ATA), referred risk stratification and thyroid nodules with intermediate- and low-suspicion patterns are difficult to diagnose. The objective of this study is to evaluate the diagnostic performance of contrast-enhanced ultrasonography (CEUS) and elastosonography (ES) for the differentiation of these thyroid nodules. From November 2011 to June 2016, a total of 163 thyroid nodules with intermediate- and low-suspicion patterns in 150 consecutive patients at our hospital were studied before surgery. With surgical pathology as the standard, the diagnostic value of CEUS and ES was analyzed. There were 29 (17.8%) malignant lesions and 134 (82.2%) benign lesions. The enhancement patterns of CEUS, the echogenicity, and the elastography were significantly different between malignant and benign lesions (P < 0.05). Heterogenous enhancement was more common in malignant nodules, and the sensitivity, specificity, positive predictive value, negative predictive value, and odds ratio were 51.7, 88.1, 48.4, 89.4, and 10.1%, respectively. The diagnostic accuracy of CEUS was better than the conventional ultrasound [area under the curve (AUC), 0.729 vs. 0.616, P = 0.021]. The enhancement patterns of CEUS were helpful in the differential diagnosis of thyroid nodules with intermediate and low suspicion.

Comparison among TIRADS (ACR TI-RADS and KWAK- TI-RADS) and 2015 ATA Guidelines in the diagnostic efficiency of thyroid nodules.

PURPOSE: To compare the value of Thyroid Imaging Reporting and Data Systems proposed by Kwak (KWAK-TIRADS) and ACR (ACR TI-RADS) and 2015 American Thyroid Association (ATA) guidelines in the diagnosis of surgically resected thyroid nodules. METHODS: From January 2015 to December 2015, 2544 thyroid nodules in 1758 patients who underwent thyroidectomy at our center were included. The KWAK-TIRADS category, ACR TI-RADS and ultrasound (US) pattern based on ATA guidelines were assigned to each thyroid nodule. Nodules were divided into groups according to their maximal diameter further. RESULTS: Of all the nodules, 863 (33.9%) were benign, whereas 1681 (66.1%) were malignant. The malignancy percentage of ACR TI-RADS category 1, 2, 3, 4, and 5 were 0%, 1.3%, 9.1%, 52.5%, and 88.8%, respectively. KWAK-TIRADS and ATA guidelines showed a better diagnostic efficiency than ACR TI-RADS (P < 0.01). ACR TI-RADS demonstrated a higher specificity (79.7%, P < 0.05), whereas the ATA US pattern had a higher sensitivity (95.5%, P < 0.01). The TIRADS (KWAK-TIRADS and ACR TI-RADS) category and ATA guidelines performed better in differentiating nodules >1 cm. KWAK-TIRADS showed better diagnostic efficiency than the other methods in differentiating nodules >1 cm (AUC: 0.92, P < 0.01). CONCLUSIONS: KWAK-TIRADS and ATA guidelines provide a better diagnostic efficiency than ACR TI-RADS. The TIRADS (KWAK-TIRADS and ACR TI-RADS) category and ATA guidelines perform better in differentiating nodules >1 cm than nodules ≤1 cm. KWAK-TIRADS perform better in differentiating nodules >1 cm than other methods.