Application of color doppler ultrasound and US shear wave elastography with connective tissue growth factor in the risk assessment of papillary thyroid carcinoma.

BACKGROUND: This study aims to investigate the role of shear wave elastography (SWE) and connective tissue growth factor (CTGF) in the assessment of papillary thyroid carcinoma (PTC) prognosis. METHODS: CTGF expression was detected with immunohistochemistry. Clinical and pathological data were collected. Parameters of conventional ultrasound combined with SWE were also collected. The relationship among CTGF expression, ultrasound indicators, the elastic modulus and the clinicopathological parameters were analyzed. RESULTS: Univariate analysis showed that patients with high risk of PTC were characterized with male, Uygur ethnicity, increased expression of CTGF, convex lesions, calcified, incomplete capsule, intranodular blood flow, rear echo attenuation, cervical lymph node metastasis, lesions larger than 1 cm, psammoma bodies, advanced clinical stage, increased TSH and high value in the shear modulus (P < 0.05). Multivariate analysis demonstrated that the risk factors of high expression of CTGF according to contribution size order were irregular shape, aspect ratio ≥ 1, and increased TSH. The logistic regression model equation was Logit (P) = 1.153 + 1.055 × 1 + 0.926 × 2 + 1.190 × 3 and the Area Under Curve value of the logistic regression was calculated to be 0.850, with a 95% confidence interval of 0.817 to 0.883. CONCLUSION: SWE and CTGF are of great value in the risk assessment of PTC. The degree of fibrosis of PTC is closely related to the prognosis. The hardness of PTC lesions and the expression level of CTGF are correlated with the main indexes of conventional ultrasound differentiating benign or malignant nodules. Irregular shape, aspect ratio ≥ 1, and increased TSH are independent factors of CTGF.

Detection and margin assessment of thyroid carcinoma with microscopic hyperspectral imaging using transformer networks.

Significance: Hyperspectral imaging (HSI) is an emerging imaging modality for oncological applications and can improve cancer detection with digital pathology. Aim: The study aims to highlight the increased accuracy and sensitivity of detecting the margin of thyroid carcinoma in hematoxylin and eosin (H&E)-stained histological slides using HSI and data augmentation methods. Approach: Using an automated microscopic imaging system, we captured 2599 hyperspectral images from 65 H&E-stained human thyroid slides. Images were then preprocessed into 153,906 image patches of dimension 250 × 250 × 84 pixels . We modified the TimeSformer network architecture, which used alternating spectral attention and spatial attention layers. We implemented several data augmentation methods for HSI based on the RandAugment algorithm. We compared the performances of TimeSformer on HSI against the performances of pretrained ConvNext and pretrained vision transformers (ViT) networks on red, green, and blue (RGB) images. Finally, we applied attention unrolling techniques on the trained TimeSformer network to identify the biological features to which the network paid attention. Results: In the testing dataset, TimeSformer achieved an accuracy of 90.87%, a weighted F 1 score of 89.79%, a sensitivity of 91.50%, and an area under the receiving operator characteristic curve (AU-ROC) score of 97.04%. Additionally, TimeSformer produced thyroid carcinoma tumor margins with an average Jaccard score of 0.76 mm. Without data augmentation, TimeSformer achieved an accuracy of 88.23%, a weighted F 1 score of 86.46%, a sensitivity of 85.53%, and an AU-ROC score of 94.94%. In comparison, the ViT network achieved an 89.98% accuracy, an 88.14% weighted F 1 score, an 84.77% sensitivity, and a 96.17% AU-ROC. Our visualization results showed that the network paid attention to biological features. Conclusions: The TimeSformer model trained with hyperspectral histological data consistently outperformed conventional RGB-based models, highlighting the superiority of HSI in this context. Our proposed augmentation methods improved the accuracy, the F 1 score, and the sensitivity score.

Ultrasound-based nomogram to predict the recurrence in papillary thyroid carcinoma using machine learning.

BACKGROUND AND AIMS: The recurrence of papillary thyroid carcinoma (PTC) is not unusual and associated with risk of death. This study is aimed to construct a nomogram that combines clinicopathological characteristics and ultrasound radiomics signatures to predict the recurrence in PTC. METHODS: A total of 554 patients with PTC who underwent ultrasound imaging before total thyroidectomy were included. Among them, 79 experienced at least one recurrence. Then 388 were divided into the training cohort and 166 into the validation cohort. The radiomics features were extracted from the region of interest (ROI) we manually drew on the tumor image. The feature selection was conducted using Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. And multivariate Cox regression analysis was used to build the combined nomogram using radiomics signatures and significant clinicopathological characteristics. The efficiency of the nomogram was evaluated by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Kaplan-Meier analysis was used to analyze the recurrence-free survival (RFS) in different radiomics scores (Rad-scores) and risk scores. RESULTS: The combined nomogram demonstrated the best performance and achieved an area under the curve (AUC) of 0.851 (95% CI: 0.788 to 0.913) in comparison to that of the radiomics signature and the clinical model in the training cohort at 3 years. In the validation cohort, the combined nomogram (AUC = 0.885, 95% CI: 0.805 to 0.930) also performed better. The calibration curves and DCA verified the clinical usefulness of combined nomogram. And the Kaplan-Meier analysis showed that in the training cohort, the cumulative RFS in patients with higher Rad-score was significantly lower than that in patients with lower Rad-score (92.0% vs. 71.9%, log rank P < 0.001), and the cumulative RFS in patients with higher risk score was significantly lower than that in patients with lower risk score (97.5% vs. 73.5%, log rank P < 0.001). In the validation cohort, patients with a higher Rad-score and a higher risk score also had a significantly lower RFS. CONCLUSION: We proposed a nomogram combining clinicopathological variables and ultrasound radiomics signatures with excellent performance for recurrence prediction in PTC patients.

Predictors of lateral lymph node metastasis and skip metastasis in patients with papillary thyroid microcarcinoma.

Background: Papillary thyroid microcarcinoma (PTMC) is characterized by its favorable prognosis and potential for active surveillance (AS) as a management option. However, the presence of cervical lymph node (LN) metastasis, especially lateral LN metastasis, significantly impacts management and prognosis. Previous studies have focused on post-surgery risk factors for cervical LN metastasis. This study aims to identify predictors of lateral LN metastasis by analyzing pre-operative ultrasonographic findings alongside clinicopathological factors. Methods: A retrospective review of medical records was conducted for patients with PTMC who underwent surgery at Chonnam National University Hwasun Hospital between 2004 and 2013. This is a case-control study that compares patients with lateral LN metastasis (N1b) to age- and sex-matched patients without LN metastasis (N0). Subgroup analysis was performed to evaluate risk factors of skip metastasis. Results: The study included 90 patients with PTMC with lateral LN metastasis (N1b) and 268 age- and sex-matched patients without LN metastasis (N0). The mean age was 49.3 years, and female patients were dominant in both groups. Structural recurrences of 4.4% (4/90) were observed only in the N1b group. The N1b group exhibited a higher frequency of upper lobe tumor location compared to the N0 group (38.9% vs. 16.0%, p < 0.001). There was no significant difference in the locations with the presence of invasion to adjacent organs. A higher proportion of non-parallel shape was observed in the N1b group than the N0 group (80.0% vs. 66.0%, p = 0.013). There were no differences in echogenicity, sonographic feature, margin, and AP diameter of the thyroid gland between the two groups. In multivariate analysis, independent risk factors for lateral LN metastasis included extrathyroidal extension, multiplicity, upper lobe tumor location, and non-parallel shape. Skip metastasis in patients with PTMC was associated with upper lobe tumor location. Conclusion: Detailed ultrasound examinations, evaluating tumor location, number, orientation, and the presence of ETE, are crucial in accurately predicting lateral LN metastasis especially when primary tumor was in the upper lobe to avoid missing skip metastasis. These evaluations can help guide the decision between AS and immediate surgery in patients with PTMC.

Predictive value of an ultrasound-based radiomics model for central lymph node metastasis of papillary thyroid carcinoma.

Purpose: We aimed to explore the predictive value of an ultrasound-based radiomics model for the central lymph node metastasis of papillary thyroid carcinoma. Methods: A total of 126 patients with papillary thyroid carcinoma treated between February 2021 and February 2023 were retrospectively enrolled and assigned into metastasis group (n=59, with cervical central lymph node metastasis) or non-metastasis group (n=67, without metastasis) based on surgical and pathological findings. Intergroup comparisons were conducted on the results of contrast-enhanced ultrasonography, preoperative conventional ultrasonography, as well as real-time shear wave elastography. Results: The maximum lesion diameter, echo, margin, capsule invasion, calcification, average elasticity modulus (Eavg), rising time (RT), and peak intensity (PI) had diagnostic value for papillary thyroid carcinoma, and their combination exhibited higher diagnostic value (area under the curve: 0.817). The logistic regression model was built, and the maximum lesion diameter, hypoechoic/extremely hypoechoic, lobulated or irregular margin (95% confidence interval: 1.451-6.755), capsule invasion, microcalcification/macrocalcification or peripheral calcification, high-level Eavg, low-level RT and high-level PI served as risk elements affecting papillary thyroid carcinoma from the aspect of central lymph node metastasis (odds ratio>1, P<0.05). According to the logistic regression model, the model was reliable and stable (area under the curve: 0.889, P<0.05). Conclusion: The established ultrasound-based radiomics model can be utilized for early identifying the central lymph node metastasis of papillary thyroid carcinoma.

Role of ultrasound in predicting telomerase reverse transcriptase (TERT) promoter mutation in follicular thyroid carcinoma.

Telomerase reverse transcriptase (TERT) promoter mutations are associated with tumor aggressiveness. This study aimed to demonstrate the ultrasonographic (US) features of TERT promoter-mutated follicular thyroid cancer (FTC) and evaluate their predictive performance. A total of 63 patients with surgically confirmed FTC between August 1995 and April 2021 were included. All data were available for analysis of preoperative US findings and TERT promoter mutation results. Genomic DNA was extracted from the archived surgical specimens to identify TERT promoter mutations. Logistic regression analysis was performed to compare US findings between TERT promoter-mutated and wild-type FTCs. Of the 63 patients with FTC, 10 (15.9%) had TERT promoter mutations. TERT promoter-mutated FTCs demonstrated significantly different US suspicion categories compared to wild-type FTCs (Ps = 0.0054 for K-TIRADS and 0.0208 for ACR-TIRADS), with a trend toward an increasing prevalence of the high suspicion category (40.0% for both K-TIRADS and ACR-TIRADS; Ps for trend = 0.0030 for K-TIRADS and 0.0032 for ACR-TIRADS). Microlobulated margins and punctate echogenic foci were independent risk factors associated with TERT promoter mutation in FTC (odds ratio = 9.693, 95% confidence interval = 1.666-56.401, p = 0.0115 for margins; odds ratio = 8.033, 95% confidence interval = 1.424-45.309, p = 0.0182 for punctate echogenic foci). There were no significant differences in the composition and echogenicity of the TERT promoter-mutated and wild-type FTCs. TERT promoter-mutated FTCs were categorized more frequently as high suspicion by the K-TIRADS and ACR-TIRADS. Based on US findings, the independent risk factors for TERT promoter mutations in FTC are microlobulated margins and punctate echogenic foci.

Combining CEUS and ultrasound parameters in thyroid nodule and cancer diagnosis: a TIRADS-based evaluation.

Contrast-enhanced ultrasonography (CEUS) has been established as a diagnostic tool for assessing microvascularization, essential for understanding angiogenesis in neoplastic development. AIM: This study assesses the effectiveness of CEUS as a supplementary tool to TIRADS in enhancing the ultrasound-based diagnosis of thyroid cancer. METHODS AND MATERIALS: Over one year, 157 nodules in 133 patients, with predominantly solid thyroid nodules, were examined using ultrasound and CEUS and underwent thyroidectomy, allowing for a comparison of ultrasound findings with pathological reports. RESULTS: Thyroid cancer was identified in 31.21% (49/157) of cases. Significant CEUS high-risk features included inhomogeneous enhancement, enhancement defects, and complete hypoenhancement (AUC 0.818, 0.767, 0.864 respectively). Nodules exhibiting any of these features were classified as high-risk in CEUS. The diagnostic performance of TIRADS improved when combined with CEUS, with AUC increasing from 0.707 to 0.840 and improved sensitivity. CONCLUSION: The integration of CEUS with TIRADS significantly enhances the diagnostic accuracy and specificity in identifying thyroid cancer. This combination proves to be a more effective method for risk stratification and diagnosis, highlighting the value of CEUS as an adjunctive tool in thyroid cancer evaluation.

Deep learning-based cell segmentation for rapid optical cytopathology of thyroid cancer.

Fluorescence polarization (Fpol) imaging of methylene blue (MB) is a promising quantitative approach to thyroid cancer detection. Clinical translation of MB Fpol technology requires reduction of the data analysis time that can be achieved via deep learning-based automated cell segmentation with a 2D U-Net convolutional neural network. The model was trained and tested using images of pathologically diverse human thyroid cells and evaluated by comparing the number of cells selected, segmented areas, and Fpol values obtained using automated (AU) and manual (MA) data processing methods. Overall, the model segmented 15.8% more cells than the human operator. Differences in AU and MA segmented cell areas varied between - 55.2 and + 31.0%, whereas differences in Fpol values varied from - 20.7 and + 10.7%. No statistically significant differences between AU and MA derived Fpol data were observed. The largest differences in Fpol values correlated with greatest discrepancies in AU versus MA segmented cell areas. Time required for auto-processing was reduced to 10 s versus one hour required for MA data processing. Implementation of the automated cell analysis makes quantitative fluorescence polarization-based diagnosis clinically feasible.

Nomogram model of serum thymidine kinase 1 combined with ultrasonography for prediction of central lymph node metastasis risk in patients with papillary thyroid carcinoma pre-surgery.

Objective: The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) pre-surgery. Methods: Patients with PTC pre-surgery in January 2021 to February 2023 were divided into three cohorts: the observation cohort (CLNM, n = 140), the control cohort (NCLNM, n = 128), and the external verification cohort (CLNM, n = 50; NCLNM, n = 50). STK1p was detected by an enzyme immunodot-blot chemiluminescence analyzer and clinical parameters were evaluated by ultrasonography. Results: A suitable risk threshold value for STK1p of 1.7 pmol/L was selected for predicting CLNM risk by receiver operating characteristic (ROC) curve analysis. Multivariate analysis identified the following six independent risk factors for CLNM: maximum tumor size >1 cm [odds ratio (OR) = 2.406, 95% confidence interval (CI) (1.279-4.526), p = 0.006]; capsule invasion [OR = 2.664, 95% CI (1.324-5.360), p = 0.006]; irregular margin [OR = 2.922; 95% CI (1.397-6.111), p = 0.004]; CLN flow signal [OR = 3.618, 95% CI (1.631-8.027), p = 0.002]; tumor-foci number ≥2 [OR = 4.064, 95% CI (2.102-7.859), p < 0.001]; and STK1p ≥1.7 pmol/L [OR = 7.514, 95% CI (3.852-14.660), p < 0.001]. The constructed nomogram showed that the area under the ROC curve for the main dataset was 0.867 and that for the validation dataset was 0.830, exhibiting effectivity, and was recalculated to a total score of approximately 383. Through monitoring the response post-surgery, all patients were assessed as tumor-free at 12 months post-surgery, which was significantly associated with a reduction in STK1p to disease-free levels. Conclusion: We demonstrate for the first time that a novel nomogram including STK1p combined with ultrasonography can assist in the clinical prevention of CLNM, by facilitating timely, individualized prophylactic CLNM dissection, thereby reducing the risk of secondary surgery and the probability of recurrence.

Comparison the accuracy of thyroid sono-elastography vs. ultrasound-guided fine needle aspiration cytology with thyroid malignancy diagnosis histopathology.

Objective. The intend of the present study was to assess the diagnostic performance of strain elastography in investigating the thyroid nodule malignancy taking the surgical biopsy as a gold standard reference test. Methods. The study included 120 patients with 123 thyroid nodules, of which 67 had total thyroidectomy. The American College of Radiology Thyroid Imaging Reporting and Data Systems (ACR-TIRADS) were evaluated for all nodules. All suspicious nodules were referred for a fine needle aspiration cytology (FNAC) if they fulfilled the required size. Strain elastography was performed for each suspicious nodule. Ultrasound-guided FNAC was performed for all suspicious nodules. Total thyroidectomy was performed in those whom the suspicious nodules were proven by FNAC. Results. Strain ratio had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of 84%, 81%, 95%, 85%, and 84%, respectively, with a cut point 1.96. Elasticity score had a sensitivity, specificity, PPV, NPV, and diagnostic accuracy of 100%, 80%, 95%, 85% and 87%, respectively, with a cut point 0.96. The elasticity score had a statistically significantly odds ratio for detecting the benignity 3.9 C. I (1.6-9.3). Conclusion. Strain elastography has a high diagnostic performance in detecting the malignant as well as benign nodules, thus it can limit the rate of unneeded FNAC or surgery especially among B3 and B4 groups with indeterminate cytology.

Diagnostic value of combined ultrasound contrast and elastography for differentiating benign and malignant thyroid nodules: a meta-analysis.

The diagnostic value of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules is still controversial, so we used meta-analysis to seek controversial answers. The PubMed, OVID, and CNKI databases were searched according to the inclusion and exclusion criteria. The literature was selected from the establishment of each database to February 2024. The QUADAS-2 tool assessed diagnostic test accuracy. SROC curves and Spearman's correlation coefficient were made by Review Manager 5.4 software to assess the presence of threshold effects in the literature. Meta-Disc1.4 software was used for Cochrane-Q and χ2 tests, which be used to evaluate heterogeneity, with P-values and I2 indicating heterogeneity levels. The appropriate effect model was selected based on the results of the heterogeneity test. Stata18.0 software was used to evaluate publication bias. The diagnostic accuracy of contrast-enhanced ultrasound combined with ultrasound elastography for benign and malignant thyroid nodules was evaluated by calculating the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, DOR, and area under the SROC curve. A total of 31 studies included 3811 patients with 4718 nodules were analyzed. There is no heterogeneity caused by the threshold effect, but there is significant non-threshold heterogeneity. Combined diagnostic metrics were: sensitivity = 0.93, specificity = 0.91, DOR = 168.41, positive likelihood ratio = 10.60, and negative likelihood ratio = 0.07. The SROC curve area was 0.97. Contrast-enhanced ultrasound and elastography show high diagnostic accuracy for thyroid nodules, offering a solid foundation for early diagnosis and treatment.Trial registration. CRD42024509462.

Targeted sequencing of DNA/RNA combined with radiomics predicts lymph node metastasis of papillary thyroid carcinoma.

OBJECTIVE: The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice. METHODS: Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics. RESULTS: 172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATMMUT) was frequently accompanied by BRAFMUT, TERTMUT or gene fusions. ATMMUT alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAFV600E, KRASG12R or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%. CONCLUSIONS: Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.

Assessing Krenning's score on 68 Ga-DOTATATE PET-CT and miPSMA score on 68 Ga-PSMA-11 PET-CT in TENIS: a comparison with FDG PET/CT and examining the feasibility of targeted radionuclide therapy.

OBJECTIVES: The objective of this study was to assess receptor expression in metastatic differentiated thyroid carcinoma patients with progressive elevated thyroglobulin and negative iodine scintigraphy, we used 68 Ga-DOTATATE [Gallium-68 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE)] (Krenning's score) and 68 Ga-PSMA-11 (Gallium-68 prostate-specific membrane antigen-11) PET-computed tomography (CT) [molecular imaging prostate-specific membrane antigen (miPSMA) score]. Patients with Krenning's score 3 and above and miPSMA score 2 and above were considered to determine the incidence of patients, who would qualify for treatment with 177 Lu-DOTATATE/PSMA [Lutetium-177 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE)/prostate-specific membrane antigen]-based therapy. In addition, we compared 68 Ga-DOTATATE and 68 Ga-PSMA-11 PET-CT with 2-deoxy-2-[F-18]fluoroglucose ( 18 F-FDG) PET-CT (using maximum standardized uptake value). MATERIALS AND METHODS: A total of 74 patients with histopathologically proven metastatic differentiated thyroid carcinoma with thyroglobulin elevation and negative iodine scintigraphy syndrome were studied retrospectively. They all had 18 F-FDG, 68 Ga-DOTATATE, and 68 Ga-PSMA-11 PET-CT scans available for undertaking this analysis. The lesions detected by 68 Ga-DOTATATE and 68 Ga-PSMA-11 were evaluated using Krenning's and miPSMA scores. In addition, quantitative comparisons of maximum standardized uptake values for 68 Ga-DOTATATE and 68 Ga-PSMA-11, as well as with 18 F-FDG, were conducted. RESULTS: Patient-wise analysis revealed positivity rates of 40.5% for 68 Ga-DOTATATE, 41.89% for 68 Ga-PSMA-11, and 75.67% for 18 F-FDG. Among the 74 patients, 14 (18.91%) were deemed eligible for 177 Lu-DOTATATE/PSMA-617 therapy based on Krenning's score of 3 and above both/either miPSMA score of 2 and above on 68 Ga-DOTATATE or 68 Ga-PSMA-11 PET-CT. Within this subgroup, seven out of 74 patients (9.45%) were eligible for 177 Lu-DOTATATE therapy, and nine out of 74 patients (12.16%) were eligible for 177 Lu-PSMA-targeted therapy. Four patients were eligible for both therapies. CONCLUSION: Among thyroglobulin elevation and negative iodine scintigraphy patient's subgroup, 9.45% could qualify for 177 Lu-DOTATATE and 12.16% for 177 Lu-PSMA-617. Four were eligible for both therapies. Given the lack of effective therapies, this subset of patients warrants consideration for radionuclide therapy exploration.

131 I Uptake in a Left Cerebral Infarct on Posttherapy Whole-Body Scan.

ABSTRACT: A 75-year-old woman with papillary thyroid carcinoma who underwent 131 I radioiodine treatment was incidentally found to have an established left cerebral infarct demonstrating 131 I uptake on posttherapy whole-body scan. False-positive iodine accumulation can occur in benign processes and other malignancies, necessitating awareness among nuclear medicine physicians to avoid misdiagnosing metastatic disease. SPECT/CT can be utilized to enhance diagnostic accuracy when needed.

Unusual Achalasia Presentation Detected on 131 I SPECT/CT in a Papillary Thyroid Carcinoma Patient.

ABSTRACT: Various factors leading to unexpected false-positive 131 I uptake have been extensively studied in patients with differentiated thyroid carcinoma. In this case, we present a patient who underwent achalasia surgery and subsequently exhibited abnormal 131 I uptake on SPECT/CT imaging. The patient was a known case of papillary thyroid carcinoma that suggested to 131 I therapy. 131 I SPECT/CT showed linear increased activity in the distended esophagus.

The role of [18F]F-DOPA PET/CT in diagnostic and prognostic assessment of medullary thyroid cancer: a 15-year experience with 109 patients.

Objective: Correct diagnosis and prognostic evaluation of medullary thyroid cancer (MTC) are crucial to treat patients. The purpose of this study was to evaluate the diagnostic and prognostic value of [18F]F-DOPA PET/CT in patients with MTC. Methods: We reviewed MTC patients who underwent [18F]F-DOPA PET/CT from June 2008 to November 2023. Clinical characteristics, follow-up data, and the following [18F]F-DOPA PET/CT parameters were recorded: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and SUVmean of multiple organs. The diagnostic value of PET/CT for the detection of tumor lesions was calculated. Serum basal calcitonin (bCt) and stimulated calcitonin (sCt) were determined. Receiver operating characteristics, Kaplan-Meier, and Cox regression analyses were performed. Results: In total, 109 patients (50 women, 59 men; average age, 55 ± 14 years) were included in the analysis. The patient-related sensitivity, specificity, and accuracy of [18F]F-DOPA PET/CT were 95%, 93%, and 94%, respectively. The lesion-related sensitivity, specificity, and accuracy were 65%, 99%, and 72%, respectively. The optimal cutoff values of bCt, sCt, and CEA to obtain positive [18F]F-DOPA PET/CT results were 64 pg/mL, 1808 pg/mL, and 4 µg/L, respectively. Patients with negative [18F]F-DOPA PET/CT had longer overall survival than patients with positive [18F]F-DOPA PET/CT results (P = 0.017). Significant positive correlations were found between bCt, sCt, and CEA with SUVmax, SUVmean, and MTV of [18F]F-DOPA PET/CT (P < 0.001). [18F]F-DOPA PET/CT results and MTV may be useful for the evaluation of the prognosis of patients with recurrent MTC, while age and MTV were independent prognostic factors in patients with primary MTC. For all patients, SUVmean of the left kidney, liver, aorta, and pancreas might be used to independently predict OS. Conclusion: [18F]F-DOPA PET/CT had great value for diagnosis and prognostic assessment in patients with MTC. The DOPA PET/CT parameter SUVmean and MTV showed significant association with OS.

PSMA-Avid Liver Metastasis in a Case of Prostate Carcinoma and Poorly Differentiated Thyroid Carcinoma.

ABSTRACT: Although PSMA-targeted PET imaging is predominantly used for prostate carcinoma (PC), it has also been reported for thyroid carcinoma (TC). A 77-year-old man had a liver metastasectomy for poorly differentiated TC, which had elevated 18 F-FDG uptake. Two years later, he was diagnosed with acinar-type modified Gleason score of 7 (3 + 4) PC. Four years later, he had metastatic liver lesions that had no radioactive iodine and 18 F-FDG avidity. These lesions were 68 Ga-PSMA avid, and the biopsy confirmed TC metastasis. This case emphasizes the importance of 68 Ga-PSMA-based imaging in poorly differentiated TC and pathological confirmation for lesions that were 68 Ga-PSMA-positive.

Efficacy of Empirical 131 I Radioiodine Therapy in Well-Differentiated Thyroid Carcinoma Patients With Thyroglobulin-Elevated Negative Iodine Scintigraphy Syndrome : A Systematic Review and Meta-analysis.

OBJECTIVES: This study aimed to perform a systematic review and meta-analysis on the efficacy of empirical high-dose radioiodine therapy in treating differentiated thyroid cancer patients with thyroglobulin (Tg)-elevated negative iodine scintigraphy (TENIS) syndrome. METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify relevant studies published until April 2022. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and registered in an international prospective register of systematic reviews (PROSPERO). Meta-analyses of proportions and odds ratios were performed to assess the beneficial effect of empirical high-dose radioiodine therapy in patients with TENIS syndrome. Subgroup analysis was also performed according to the presence of micrometastasis or macrometastasis. RESULTS: We identified 14 studies including 690 patients who received empirical high-dose radioiodine therapy for TENIS syndrome. Those who had micrometastasis exhibited additional lesions not previously observed on diagnostic whole-body scan (prop = 0.64, 95% confidence interval [CI], 0.51-0.77) and had reduced serum Tg levels (prop = 0.69; 95% CI, 0.52-0.84) after empirical radioiodine treatment. No such findings were observed among patients with macrometastasis. Moreover, we found that the empirical radioiodine treatment group had lower serum Tg levels than did controls (odds ratio = 0.27; 95% CI, 0.09-0.87), which suggests a lower risk of disease progression. CONCLUSIONS: Our findings indicate that empirical high-dose radioiodine therapy promoted beneficial effects and could be recommended for patients with TENIS syndrome, especially those with micrometastasis.

Clinical risk factors and cancer risk of thyroid imaging reporting and data system category 4 A thyroid nodules.

PURPOSE: Beyond the Thyroid Imaging Reporting and Data System (TIRADS) classification of thyroid nodules, additional factors must be weighed in the decision to perform fine needle aspiration (FNA). In this study, we aimed to identify risk factors for malignancy in patients with ultrasound-classified Chinese-TIRADS (C-TIRADS) 4 A nodules. METHODS: Patients who underwent thyroid FNA at our institution between May 2021 and September 2022 were enrolled. We collected demographic data, including age, sex, previous radiation exposure, and family history. An in-person questionnaire was used to collect lifestyle data, such as smoking habits and alcohol consumption. Body mass index (BMI) was calculated. The serum levels of thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured. Prior to FNA, ultrasonic inspection reports were reviewed. The cytologic diagnoses for FNA of thyroid nodules followed the Bethesda System for Reporting Thyroid Cytopathology (2017). RESULTS: Among the 252 C-TIRADS 4 A nodules, 103 were malignant. Compared to those in the benign group, the patients in the malignant group had a younger age (42.2 ± 13.6 vs. 51.5 ± 14.0 years, P < 0.001). Logistic regression showed that advanced age was associated with a lower risk of malignancy in C-TIRADS 4 A nodules (OR = 0.95, 95% CI 0.93 ~ 0.97, P < 0.001). We demonstrated a decreased risk of malignancy in patients with 48.5 years or older. CONCLUSION: Advanced age was associated with a decreased risk of malignancy in patients with C-TIRADS 4 A nodules. This study indicated that in addition to sonographic characteristics, patient age should be considered when assessing the risk of malignancy.

A novel low-background nitroreductase fluorescent probe for real-time fluorescence imaging and surgical guidance of thyroid cancer resection.

Thyroid cancer always appears insidiously with few noticeable clinical symptoms. Due to its limitations, conventional ultrasound imaging can lead to missed or misdiagnosed cases. Surgery is still the primary treatment method of thyroid cancer, but removal of surrounding healthy tissues to minimize recurrence leads to overtreatment and added patient suffering. To address this challenge, herein, a nitroreductase (NTR) fluorescent probe, Ox-NTR, has been developed for detecting thyroid cancer and tracking the surgical removal of thyroid tumors by fluorescence imaging. The conjugated structure of oxazine 1 was disrupted, significantly reducing the issue of high background signals, thus effectively achieving low background fluorescence. Under hypoxic conditions, the nitro group of Ox-NTR can be reduced to an amine and subsequently decomposed into oxazine 1, emitting intense red fluorescence. Ox-NTR has a low detection limit of 0.09 µg/mL for NTR with excellent photostability and selectivity. Cellular studies show that Ox-NTR can effectively detect NTR levels in hypoxic thyroid cancer cells. Moreover, the ability of Ox-NTR of rapid response to thyroid cancer in vivo is confirmed by fluorescence imaging in mice, distinguishing tumors from normal tissues due to its superior low background fluorescence. Utilizing this fluorescence imaging method during surgical resection can guide the removal of tumors, preventing both missed tumor tissues and accidental removal of healthy tissue. In summary, the novel Ox-NTR offers precise detection capabilities that provide significant advantages over traditional imaging methods for thyroid cancer diagnosis and treatment, making it a valuable tool to guide tumor removal in surgical procedures.