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Background: Papillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer, and the presence of extrathyroidal extension (ETE) significantly impacts treatment decisions and prognosis. Accurate preoperative detection of ETE remains challenging, highlighting the need to evaluate advanced imaging techniques.This systematic review and meta-analysis aimed to investigate the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting extrathyroidal extension (ETE) among patients diagnosed with papillary thyroid carcinoma (PTC). Method: We conducted a comprehensive search of global databases including PubMed, Web of Science, EMBASE, and the Cochrane Library, spanning from inception to November 03, 2024. We included studies that utilized preoperative MRI to evaluate the presence of ETE. Quality assessment was carried out using the Joanna Briggs Institute (JBI) standard checklists. Data analysis was performed using Comprehensive Meta-Analysis (CMA) software version 3. The study protocol was registered in PROSPERO (CRD42024499536). Result: Six studies were included in our final quantitative analysis. The included studies were classified into two groups; the first group focused on evaluating the accuracy of MRI in detecting ETE, while the second group assessed the apparent diffusion coefficient (ADC). The accuracy of MRI for overall ETE, minimal ETE (mETE), and gross ETE (gETE) was 81.0% (95% CI: 76.9%-85.6%), 72.9% (95% CI: 66.2%-78.6%), and 83.3% (95% CI: 75.2%-89.1%), respectively. MRI demonstrated a statistically significant difference in detecting gETE compared to mETE (OR = 1.85, 95% CI: 1.01–3.37, P-value = 0.045). Our analysis showed that the ADC of the lesion for b-value 500 is lower in patients with ETE compared to those without ETE (SMD = 0.95, 95% CI: 0.28–1.62, P-value = 0.005). Conclusion: Our findings demonstrate that MRI has substantial accuracy in detecting ETE in PTC, especially for gross ETE. This suggests MRI could be a valuable tool in preoperative planning, helping to guide surgical decision-making by more precisely identifying patients at higher risk. However, the limited number of studies underscores the need for further research to confirm MRI's role in routine clinical practice and to refine imaging protocols for more accurate differentiation between minimal and gross ETE. [ABSTRACT FROM AUTHOR]

Objectives. The presence of extrathyroidal extension (ETE) in patients with differentiated thyroid cancer (DTC) serves as a significant prognostic indicator. Consequently, the staging of DTC is categorized into extensive ETE and gross ETE that solely impacts the strap muscles (gross strap muscle invasion [gSMI]). However, there is a lack of sufficient evidence concerning the relationship between gSMI and prognosis, particularly in terms of tumor size. Methods. Relevant literature was searched in Medline, Embase, Cochrane Library, and KoreaMed. All procedures were conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and carried out by two independent reviewers. The meta-analysis utilized a random-effects model to account for the diversity of the studies. Risk of Bias for Nonrandomized Studies (RoBANS) version 2.0, an evaluation tool for non-randomized studies, was employed to assess the quality of the selected research. Clinical data from observational studies that examined the relationship between the degree of ETE and prognosis were gathered, and a meta-analysis was conducted. Results. Eighteen observational studies were included in this analysis. Subgroup analyses were conducted for each outcome. The findings revealed that the recurrence rate (odds ratio [OR], 2.498), disease-specific mortality (risk ratio [RR], 2.984), overall mortality (RR, 1.361), and lymph node (LN) metastasis (OR, 5.355) were significantly higher in patients with gSMI than in those without ETE. However, when the analysis was restricted to tumors measuring 4 cm or smaller, no significant differences in prognostic outcomes were observed, with the exception of LN metastasis. Conclusion. gSMI negatively impacts prognosis; however, this correlation diminishes with smaller tumor sizes. Thus, a more cautious approach is warranted during the treatment process.

Extrathyroidal extension was related with worse survival for patients with papillary thyroid carcinoma. For its preoperative evaluation, we measured and compared the predicting value of sonographic method and ultrasonic radiomics method in nodules of papillary thyroid carcinoma.

The article "Commentary: Meta-analysis of the effect and clinical significance of Delphian lymph node metastasis in papillary thyroid cancer" by Shanshan Wu critiques a study by Chen et al. on Delphian lymph node metastasis in papillary thyroid cancer. Wu identifies data entry errors and issues with forest plots in Chen's analysis, suggesting modifications for accuracy. The reanalysis shows that male papillary thyroid carcinoma patients are more likely to have Delphian lymph node metastasis, supporting the need for tailored management strategies based on gender disparities in cancer incidence and prognosis. The study emphasizes the importance of assessing Delphian lymph nodes in thyroid cancer patients for personalized treatment planning. [Extracted from the article]

Background and objectives: The aim of this study was to evaluate the clinical–pathological profile in young patients with thyroid cancer. Materials and methods: We realized a retrospective study on patients with thyroid neoplasms who underwent surgery at the "Pius Brinzeu" County Clinical Emergency Hospital in Timisoara, Romania. A comparative analysis of some parameters between two groups, young patients (<45 years) versus patients ≥45 years, was performed. Results: A total of 211 patients met the study inclusion criteria, mostly females (86.26%) with a female/male ratio of 6.81:1. In patients <45 years old (25.64%), papillary thyroid carcinoma was identified in 51.85% of cases; in 53.85% of cases, the tumor was >1 cm; 13.46% had extrathyroidal extension (p = 0.0430); 21.15% capsule invasion (p = 0.1756); 23.08% lympho-vascular invasion (p = 0.0048); and 13.46% of cases locoregional nodal invasion (p = 0.0092). Conclusions: Thyroid cancer in young people was associated with chronic lymphocytic thyroiditis and tumor progression parameters, identifying more cases of extrathyroidal extension, locoregional nodal invasion, lympho-vascular invasion and perineural invasion in young patients compared to older ones. For a better understanding of this pathology and to improve diagnosis and therapeutic management, more studies are needed for these patients. [ABSTRACT FROM AUTHOR]

Background: Despite the increasing recognition of PD-L1 as predictor of immunotherapeutic response in various malignancies, its role and prognostic significance in thyroid cancer remain underexplored and subject to debate. This study begins to address this gap by comprehensively analyzing PD-L1 expression in papillary thyroid carcinoma (PTC) and investigating its correlation with key clinicopathological variables. Methods: We conducted immunohistochemistry (IHC) to assess PD-L1 expression in whole-tissue sections from 121 primary papillary thyroid carcinoma (PTC) cases. We then analyzed the correlations between PD-L1 expression and various clinicopathological variables. Results: PD-L1 expression was detected in 33.1% of papillary thyroid carcinomas (PTCs), predominantly exhibiting weak to moderate intensity. Notably, this study found no significant correlation between PD-L1 expression and various clinicopathological variables. The lack of association with traditional factors such as age, sex, histological subtype, and tumor size suggests the complex and multifaceted nature of PD-L1 regulation in PTC. Multivariate logistic regression analysis identified chronic lymphocytic thyroiditis with oncocytic metaplasia as the sole independent predictor of PD-L1 expression (P = 0.014), underlining the potential influence of the tumor microenvironment on immune checkpoint expression in PTC. Conclusions: Our study underscores the intricate interplay between chronic lymphocytic thyroiditis with oncocytic metaplasia and PD-L1 expression in papillary thyroid carcinoma. The observed link suggests a potential avenue for therapeutic intervention using anti-PD-1/PD-L1 therapies in surgery-refractory PTC. Understanding the dynamics of immune checkpoint regulation in the context of the tumor microenvironment is crucial for devising effective treatment strategies. Future research endeavors should delve deeper into the molecular mechanisms underlying this interaction and explore its implications for patient outcomes. As the field of immunotherapy continues to evolve, our findings contribute valuable insights into the complex immunological landscape of thyroid cancer. [ABSTRACT FROM AUTHOR]

Background: Globally, the incidence of papillary thyroid cancer (PTC) has been increasing over the last few decades and it has become the second most common cancer in women in the UAE. There is some evidence to suggest that COVID-19 infection might be directly linked to the development of aggressive variants of PTC. The primary goal of this study was to compare the clinical and pathologic characteristics of thyroid cancer patients treated at the largest endocrine surgery center in Abu Dhabi before and after the COVID-19 pandemic outbreak. Methods: This retrospective cohort analysis included patients who underwent elective thyroid surgery at Burjeel Hospital between January 2018 and December 2022. Patients were divided into two groups based on when the COVID-19 outbreak started: group one, comprising patients who had surgery between January 2018 and December 2019 (the "pre-pandemic group"), and group two, comprising patients who had surgery between January 2021 and December 2022 (the "post-pandemic group"). In addition to demographic data, clinicopathological factors, such as aggressive cell type, multifocality, tumor size and location, laterality, lympho-vascular invasion, and extrathyroidal extension, were assessed. We utilized the t-paired test for parametric variables and the Chi-square test for the cross-table analysis. Results: During the study, 1141 people had thyroid surgery, with an annual average of 285 procedures. PTC cases recorded in the final histopathological samples rose from 111 in the pre-pandemic era to 182 in the post-pandemic era. Neither the female-to-male gender ratio, which was 90:21 in the pre-pandemic group and 142:40 in the post-pandemic group (p = 0.532), nor the median age, which was 39.1 and 40.1 years, respectively, varied significantly between the two groups. However, there was a significant increase between pre-pandemic and post-pandemic in the aggressive PTC variants (3% vs. 11.5%, p = 0.001), increased poor prognostic factors such as bilateral multifocality (10.8% vs. 32.4%, p = 0.000), as well as increased capsule–vascular tumor invasion (19.8% vs. 27%); on the other hand, the size of the single foci was 17 mm in the pre-pandemic group compared to 13 mm in the post-pandemic group (p = 0.001). Conclusions: A significant rise in unfavorable prognostic markers and aggressive subtypes of PTC was seen post-pandemic in thyroidectomy patients operated on at a leading endocrine surgery center in the United Arab Emirates. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this metaanalysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT. Methods: Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0. Results: In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients. Conclusion: This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer (TC) is an increasingly prevalent malignancy throughout the world. It has long been recognized that the incidence of TC is higher in women which increases with age. However, the association of gender disparity and age with TC aggressiveness and outcomes are still controversial. The aim of this study was focused on the association of age and gender with histopathological characteristics in TC. Methods: 153 patients who met the criteria, were selected. The included cases were divided into four age groups (≤24 years, 25-44 years, 45-64 years, and ≥65 years). Demographic, age and pathological parameters were compared among them. The association of gender and age with histopathological features were then evaluated. Results: Females were significantly more frequent in almost all age groups with the highest female frequency found the age group of 25- 44 years old. Females are more susceptible for TC even when they are young. The four groups showed highly significant differences regarding extrathyroidal extension (ETE) which is more aggressive in older individuals’ tumor. However, there were no significant differences regarding tumor size, multifocality, LV invasion and LN metastasis. Moreover, increasing age was significantly associated with increases risk of ETE. In addition, old patients and males were significantly more likely to have larger tumor size. Nonetheless, both gender and age non-significantly associated with multifocality and LV invasion. Conclusion: Our results confirmed that increasing age could really exert a negative prognostic effect, at least in terms of ETE risk and larger tumor size. In addition, TC risk in females was more frequent in all age groups and significantly more likely than men to present at younger, nonetheless, males represented larger tumor size. [ABSTRACT FROM AUTHOR]

Abstract Background There is a recognized need for additional approaches to improve the accuracy of extrathyroidal extension (ETE) diagnosis in papillary thyroid carcinoma (PTC) before surgery. Up to now, multimodal ultrasound has been widely applied in disease diagnosis. We investigated the value of radiomic features extracted from multimodal ultrasound in the preoperative prediction of ETE. Methods We retrospectively pathologically confirmed PTC lesions in 235 patients from January 2019 to April 2022 in our hospital, including 45 ETE lesions and 205 non-ETE lesions. MaZda software was employed to obtain radiomics parameters in multimodal sonography. The most valuable radiomics features were selected by the Fisher coefficient, mutual information, probability of classification error and average correlation coefficient methods (F + MI + PA) in combination with the least absolute shrinkage and selection operator (LASSO) method. Finally, the multimodal model was developed by incorporating the clinical records and radiomics features through fivefold cross-validation with a linear support vector machine algorithm. The predictive performance was evaluated by sensitivity, specificity, accuracy, F1 scores and the area under the receiver operating characteristic curve (AUC) in the training and test sets. Results A total of 5972 radiomics features were extracted from multimodal sonography, and the 13 most valuable radiomics features were selected from the training set using the F + MI + PA method combined with LASSO regression. The multimodal prediction model yielded AUCs of 0.911 (95% CI 0.866–0.957) and 0.716 (95% CI 0.522–0.910) in the cross-validation and test sets, respectively. The multimodal model and radiomics model showed good discrimination between ETE and non-ETE lesions. Conclusion Radiomics features based on multimodal ultrasonography could play a promising role in detecting ETE before surgery.

Background and objectives: The aim of this study was to evaluate the clinical–pathological profile in young patients with thyroid cancer. Materials and methods: We realized a retrospective study on patients with thyroid neoplasms who underwent surgery at the “Pius Brinzeu” County Clinical Emergency Hospital in Timisoara, Romania. A comparative analysis of some parameters between two groups, young patients (Results: A total of 211 patients met the study inclusion criteria, mostly females (86.26%) with a female/male ratio of 6.81:1. In patients 1 cm; 13.46% had extrathyroidal extension (p = 0.0430); 21.15% capsule invasion (p = 0.1756); 23.08% lympho-vascular invasion (p = 0.0048); and 13.46% of cases locoregional nodal invasion (p = 0.0092). Conclusions: Thyroid cancer in young people was associated with chronic lymphocytic thyroiditis and tumor progression parameters, identifying more cases of extrathyroidal extension, locoregional nodal invasion, lympho-vascular invasion and perineural invasion in young patients compared to older ones. For a better understanding of this pathology and to improve diagnosis and therapeutic management, more studies are needed for these patients.

BackgroundSubclinical hypothyroidism is the most common thyroid dysfunction. Approximately 10% of patients with thyroid cancer have subclinical hypothyroidism. There is a paucity of real-world studies examining the relationship between subclinical hypothyroidism and known correlates of invasiveness of papillary thyroid carcinoma (PTC).Materials and methodsA retrospective cohort study of 13,717 patients with PTC was conducted. Odds ratios were calculated to assess the relationship between subclinical hypothyroidism and extrathyroidal extension (ETE) after adjusting for BMI and genders. The Cancer Genome Atlas (TCGA) data were utilized for the analysis of TSHR-associated pathways, while qRT-PCR was employed to validate the expression levels of pivotal genes in the relevant signaling pathways.ResultsIn total, 13,717 PTC patients (10,769 women and 2,948 men; mean [SD] age, 42.90 [9.43] years) were included in the retrospective study. Subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.168 [95% CI, 1.028–1.327]; P=0.017). In normal-weight patients, subclinical hypothyroidism was an independent risk factor for ETE (OR adjusted, 1.287 [95% CI, 1.089–1.520]; P=0.003). However, this risk was not observed in under-weight, overweight, and obese patients. Compared to females, subclinical hypothyroidism was a higher risk factor for ETE in male patients with normal body weight (OR male=2.363 vs. OR female=1.228). Subclinical hypothyroidism was found to be a significant risk factor for ETE in the subgroup of patients younger than 38 years old (OR1 adjusted, 1.382 [95% CI, 1.032–1.852], P=0.030). The findings from Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed the involvement of the autophagy signaling pathway in TSHR/ETE/EMT regulation. Moreover, the gene expression levels demonstrated a concentration-dependent relationship between TSH intervention levels and the expression of key genes in the autophagy pathway of thyroid cancer cells.ConclusionSubclinical hypothyroidism was an independent risk factor for ETE in patients with PTC. This association was particularly significant in normal-weight and younger patients. The risk of ETE associated with subclinical hypothyroidism was higher in males compared to females. Our study indicates a potential involvement of the autophagy pathway in regulating the ETE phenotype in thyroid cancer, specifically in the context of subclinical hypothyroidism.

BackgroundEvidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT. MethodsMedline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0. ResultsIn total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P

Background: Extrathyroidal extension (ETE) significantly affects the treatment strategy for thyroid cancer. We present a new method to predict ETE of papillary thyroid carcinoma (PTC). methods: We enrolled 1 481 patients with PTCs. The ETE was classified into minimal and gross ETE. Using the novel "contact angle of the tumor on sonography" (CATS) system, we calculated optimal cutoffs for predicting ETE according to tumor location and compared the diagnostic performance to that of previous methods. Results: The optimal cutoff angles for predicting anterior minimal and gross ETE were 41.5° and 49.4°, respectively, while those for posterior ETE were 39.8° and 54.6°, respectively. The optimal cutoff angle predicting tracheal ETE was 88.0°. The diagnostic performance was comparable to that of previous methods. Conclusion: The CATS method for predicting ETE is a valuable alternative. [ABSTRACT FROM AUTHOR]

Qi He, Feihong Ji, Xinghao Fu, Zehao Li, Xinguang Qiu Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Xinguang Qiu, Email qxg0914@126.comIntroduction: Currently, there is no consensus on the specific effect of Extrathyroidal Extension (ETE) on prognosis. The purpose of our study was to study the relationship between different states of ETE and its disease-free survival rate and to determine the basic standard of Micro ETE (tumor extends through capsule only) in risk stratification.Material and Methods: We conducted a retrospective and single-center study that included the clinical data of all papillary thyroid carcinoma (PTC) patients with ETE in our hospital from 2013 to 2017 and followed them up after rigorous screening. According to ETE state, it is divided into four groups: Microscopic, Micro, Minimal, Macro. Kaplan–Meier method was used to calculate disease-free survival (DFS). Log-rank test was used to compare the differences between the groups and to polt the survival curves. P< 0.05 was considered statistically significant. Micro ETE was included in different risk stratification subgroups and their DFS was compared.Results: A total of 436 patients were included: Microscopic group N=50 (11.47%), Micro group N=74 (16.97%), Minimal group N=135 (30.96%), and Macro group N=177 (40.60%). The frequency of ETE was in strap muscles N=191, trachea N=114, laryngeal recurrent nerve N=92, and capsule N=74, etc. The 5-year DFS rate in Micro group was 95.3%, higher than that in Macro group (P< 0.05). The 5-year DFS rate of Micro ETE was 90.0% in the intermediate-risk group and 84.9% in the high-risk group when Micro ETE was included in different risk stratification subgroups.Conclusion: Micro ETE deserves more attention, has a batter prognosis than Macro ETE, and may have little effect on recurrence. It seems more appropriate to treat Micro ETE as the intermediate-risk group in risk stratification.Keywords: extrathyroidal extension, risk stratification, papillary thyroid carcinoma, prognosis

Background: There is a recognized need for additional approaches to improve the accuracy of extrathyroidal extension (ETE) diagnosis in papillary thyroid carcinoma (PTC) before surgery. Up to now, multimodal ultrasound has been widely applied in disease diagnosis. We investigated the value of radiomic features extracted from multimodal ultrasound in the preoperative prediction of ETE. Methods: We retrospectively pathologically confirmed PTC lesions in 235 patients from January 2019 to April 2022 in our hospital, including 45 ETE lesions and 205 non-ETE lesions. MaZda software was employed to obtain radiomics parameters in multimodal sonography. The most valuable radiomics features were selected by the Fisher coefficient, mutual information, probability of classification error and average correlation coefficient methods (F + MI + PA) in combination with the least absolute shrinkage and selection operator (LASSO) method. Finally, the multimodal model was developed by incorporating the clinical records and radiomics features through fivefold cross-validation with a linear support vector machine algorithm. The predictive performance was evaluated by sensitivity, specificity, accuracy, F1 scores and the area under the receiver operating characteristic curve (AUC) in the training and test sets. Results: A total of 5972 radiomics features were extracted from multimodal sonography, and the 13 most valuable radiomics features were selected from the training set using the F + MI + PA method combined with LASSO regression. The multimodal prediction model yielded AUCs of 0.911 (95% CI 0.866–0.957) and 0.716 (95% CI 0.522–0.910) in the cross-validation and test sets, respectively. The multimodal model and radiomics model showed good discrimination between ETE and non-ETE lesions. Conclusion: Radiomics features based on multimodal ultrasonography could play a promising role in detecting ETE before surgery. [ABSTRACT FROM AUTHOR]

Background: Extrathyroidal extension is a major risk factor for poor prognosis in papillary thyroid cancer. However, the effect of different degrees of extrathyroidal extension on prognosis remains controversial. We performed a retrospective study to elucidate how the extent of extrathyroidal extension in papillary thyroid cancer affected the clinical prognosis of patients and its covariates. Methods: The study included 108,426 patients with papillary thyroid cancer. We categorized the extent of extension into none, capsule, strap muscles, and other organs. Three causal inference methods for retrospective studies, namely, inverse probability of treatment weighting, standardized mortality ratio weighting, and propensity score matching analysis, were used to minimize potential selection bias. Kaplan-Meier analysis and univariate Cox regression analyses were applied to analyze the precise effect of ETE on survival in papillary thyroid cancer patients. Results: In the Kaplan-Meier survival analysis, only extrathyroidal extension into or beyond the strap muscles was statistically significant for both overall survival (OS) and thyroid cancer-specific survival (TCSS). In univariate Cox regression analyses before and after matching or weighting based on causal inference, extrathyroidal extension into soft tissues or other organs is a high-risk factor for both overall survival and thyroid cancer-specific survival. Sensitivity analysis revealed that lower overall survival was observed in patients with older age (=55) and larger tumor size (>2 cm) of papillary thyroid cancer with extrathyroidal extension into or beyond the strap muscles. Conclusions: Our study indicates that extrathyroidal extension into soft tissues or other organs is a high-risk factor in all papillary thyroid cancer. Even though invasion into the strap muscles did not seem to be a marker for poor prognosis, it still impaired the overall survival of patients with older age (≥55 years old) or larger tumor size (>2 cm). Further investigation is needed to confirm our results and to clarify further risk factors independent of extrathyroidal extension. [ABSTRACT FROM AUTHOR]

Context: Tumor size is important in determining the range of surgery in papillary thyroid carcinomas (PTCs), especially those smaller than 1 cm. Objective: We aimed to analyze the features of small PTCs with aggressive subtypes based on histological characteristics. Methods: In this retrospective study, we reviewed the medical records of 11 570 patients with PTCs smaller than or equal to 1 cm who underwent thyroidectomy between January 2009 and December 2016. Aggressive subtypes included diffuse sclerosing, solid, tall cell, columnar cell, and hobnail subtypes. Results: Among the 11 570 patients with PTCs smaller than or equal to 1 cm, 177 aggressive PTC subtypes were identified. Propensity score matching revealed 110 tumors (62.1%) with extrathyroidal extension of aggressive PTC subtypes and 451 (51.1%) nonaggressive PTC subtypes (95% CI, 0.41-0.80; P<.001). Metastatic central and lateral neck lymph nodes constituted 3.06±3.67 and 3.81± 5.39 of aggressive PTC subtypes and 1.22±2.14 and 2.85±3.79 of nonaggressive PTC subtypes, respectively (central neck nodes: 95% CI, 1.42-2.26; P<.001; lateral neck nodes: 95% CI, 2.9-5.90; P<.001). Seven patients with aggressive PTC subtypes (3.95%) and 12 with nonaggressive PTC subtypes (1.7%) exhibited recurrence. Conclusion: Aggressive subtypes of small PTC tumors smaller than or equal to 1 cm exhibited more extrathyroidal extension and neck node metastasis. This study suggests that surgeons should consider the aggressive subtypes as important factors when deciding the range of surgery in PTCs smaller than 1 cm. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. PTC patients with extrathyroidal extension (ETE) are associated with poor prognoses. The preoperative accurate prediction of ETE is crucial for helping the surgeon decide on the surgical plan. This study aimed to establish a novel clinical-radiomics nomogram based on B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) for the prediction of ETE in PTC. A total of 216 patients with PTC between January 2018 and June 2020 were collected and divided into the training set (n = 152) and the validation set (n = 64). The least absolute shrinkage and selection operator (LASSO) algorithm was applied for radiomics feature selection. Univariate analysis was performed to find clinical risk factors for predicting ETE. The BMUS Radscore, CEUS Radscore, clinical model, and clinical-radiomics model were established using multivariate backward stepwise logistic regression (LR) based on BMUS radiomics features, CEUS radiomics features, clinical risk factors, and the combination of those features, respectively. The diagnostic efficacy of the models was assessed using receiver operating characteristic (ROC) curves and the DeLong test. The model with the best performance was then selected to develop a nomogram. The results show that the clinical-radiomics model, which is constructed by age, CEUS-reported ETE, BMUS Radscore, and CEUS Radscore, showed the best diagnostic efficiency in both the training set (AUC = 0.843) and validation set (AUC = 0.792). Moreover, a clinical-radiomics nomogram was established for easier clinical practices. The Hosmer–Lemeshow test and the calibration curves demonstrated satisfactory calibration. The decision curve analysis (DCA) showed that the clinical-radiomics nomogram had substantial clinical benefits. The clinical-radiomics nomogram constructed from the dual-modal ultrasound can be exploited as a promising tool for the pre-operative prediction of ETE in PTC. [ABSTRACT FROM AUTHOR]

Background: Globally, the incidence of papillary thyroid cancer (PTC) has been increasing over the last few decades and it has become the second most common cancer in women in the UAE. There is some evidence to suggest that COVID-19 infection might be directly linked to the development of aggressive variants of PTC. The primary goal of this study was to compare the clinical and pathologic characteristics of thyroid cancer patients treated at the largest endocrine surgery center in Abu Dhabi before and after the COVID-19 pandemic outbreak. Methods: This retrospective cohort analysis included patients who underwent elective thyroid surgery at Burjeel Hospital between January 2018 and December 2022. Patients were divided into two groups based on when the COVID-19 outbreak started: group one, comprising patients who had surgery between January 2018 and December 2019 (the “pre-pandemic group”), and group two, comprising patients who had surgery between January 2021 and December 2022 (the “post-pandemic group”). In addition to demographic data, clinicopathological factors, such as aggressive cell type, multifocality, tumor size and location, laterality, lympho-vascular invasion, and extrathyroidal extension, were assessed. We utilized the t-paired test for parametric variables and the Chi-square test for the cross-table analysis. Results: During the study, 1141 people had thyroid surgery, with an annual average of 285 procedures. PTC cases recorded in the final histopathological samples rose from 111 in the pre-pandemic era to 182 in the post-pandemic era. Neither the female-to-male gender ratio, which was 90:21 in the pre-pandemic group and 142:40 in the post-pandemic group (p = 0.532), nor the median age, which was 39.1 and 40.1 years, respectively, varied significantly between the two groups. However, there was a significant increase between pre-pandemic and post-pandemic in the aggressive PTC variants (3% vs. 11.5%, p = 0.001), increased poor prognostic factors such as bilateral multifocality (10.8% vs. 32.4%, p = 0.000), as well as increased capsule–vascular tumor invasion (19.8% vs. 27%); on the other hand, the size of the single foci was 17 mm in the pre-pandemic group compared to 13 mm in the post-pandemic group (p = 0.001). Conclusions: A significant rise in unfavorable prognostic markers and aggressive subtypes of PTC was seen post-pandemic in thyroidectomy patients operated on at a leading endocrine surgery center in the United Arab Emirates.

Aim. To evaluate the diagnostic performance of radiomics features of two-dimensional (2D) and threedimensional (3D) ultrasound (US) in predicting extrathyroidal extension (ETE) status in papillary thyroid carcinoma (PTC). Patients and Methods. 2D and 3D thyroid ultrasound images of 72 PTC patients confirmed by pathology were retrospectively analyzed. The patients were assigned to ETE and non-ETE. The regions of interest (ROIs) were obtained manually. From these images, a larger number of radiomic features were automatically extracted. Lastly, the diagnostic abilities of the radiomics models and a radiologist were evaluated using receiver operating characteristic (ROC) analysis. We extracted 1693 texture features firstly. Results. The area under the ROC curve (AUC) of the radiologist was 0.65. For 2D US, the mean AUC of the three classifiers separately were: 0.744 for logistic regression (LR), 0.694 for multilayer perceptron (MLP), 0.733 for support vector machines (SVM). For 3D US they were 0.876 for LR, 0.825 for MLP, 0.867 for SVM. The diagnostic efficiency of the radiomics was better than radiologist. The LR model had favorable discriminate performance with higher area under the curve. Conclusion. Radiomics based on US image had the potential to preoperatively predict ETE. Radiomics based on 3D US images presented more advantages over radiomics based on 2D US images and radiologist. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the correlation between sonographic features and central neck lymph node metastasis (CNLM) in solitary solid papillary thyroid microcarcinoma (PTMC) with a taller-than-wide shape. Methods: A total of 103 patients with solitary solid PTMC with a taller-than-wide shape on ultrasonography who underwent surgical histopathological examination were retrospectively selected. Based on the presence or absence of CNLM, patients with PTMC were divided into a CNLM (n = 45) or nonmetastatic (n = 58) group, respectively. Clinical findings and ultrasonographic features, including a suspicious thyroid capsule involvement sign (STCS, which is defined as PTMC abutment or a disrupted thyroid capsule), were compared between the two groups. Additionally, postoperative ultrasonography was performed to assess patients during the follow-up period. Results: Significant differences were observed in sex and the presence of STCS between the two groups (p < 0.05). The specificity and accuracy of the male sex for predicting CNLM were 86.21% (50/58 patients) and 64.08% (66/103 patients), respectively. The sensitivity, specificity, positive predictive value (PPV), and accuracy of STCS for predicting CNLM were 82.22% (37/45 patients), 70.69% (41/58 patients), 68.52% (37/54 patients), and 75.73% (78/103 patients), respectively. The specificity, PPV, and accuracy of the combination of sex and STCS for predicting CNLM were 96.55% (56/58 patients), 87.50% (14/16 patients), and 67.96% (70/103 patients), respectively. A total of 89 (86.4%) patients were followed up for a median of 4.6 years, with no patient having recurrence as detected on ultrasonography and pathological examination. Conclusions: STCS is a useful ultrasonographic feature for predicting CNLM in patients with solitary solid PTMC with a taller-than-wide shape, especially in male patients. Solitary solid PTMC with a taller-than-wide shape may have a good prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background Differentiated thyroid cancer has excellent overall survival. However, around 20% of patients experience recurrent diseases after a certain time of follow-up. Therefore, identification of risk factors for recurrence is necessary to adjust treatment and surveillance planning. Methods A retrospective study was conducted of 312 patients with differentiated thyroid cancer who received surgery with and without adjuvant treatment. Clinical and pathological risk factors were analyzed for recurrences. Results After median follow-up of 57 months, 109 of 312 patients (34.9%) developed recurrences. Extrathyroidal extension and positive cervical nodes were significantly associated with recurrences (OR = 2.449, 95%CI:1.260–4.760, P = 0.008 and OR = 3.511, 95%CI:1.860–6.626, P

Abstract Background Extrathyroidal extension (ETE) is considered a major prognostic factor in papillary thyroid carcinoma (PTC). Patients with gross ETE are at increased risk of recurrence and mortality. The importance of minimal ETE still remains controversial, especially in patients with papillary thyroid microcarcinoma (PTMC). The purpose of this study was to evaluate the association between ETE and lymph node (LN) metastasis in single PTMC. Methods A retrospective analysis was performed of 1994 patients underwent thyroidectomy for PTC between 2012 and 2016 in a single institution. Patients with combined thyroid carcinoma of other types and those who underwent completion thyroidectomy were excluded. After further exclusion of PTC larger than 1 cm and multifocal tumors, 814 patients with single PTMC were included in the study. Results 72.9% patients had no ETE, 25.1% minimal ETE, and 2.1% gross ETE. ETE was associated with lymphatic invasion, perineural invasion, and vascular invasion. Patients with minimal and gross ETE were also more likely to have LN metastasis, including lateral neck metastasis, compared to those without ETE. In univariate analysis, LN metastasis was associated with male gender, conventional PTC, lymphatic invasion, perineural invasion, and ETE. In multivariate analysis, male gender (OR = 1.987; 95% CI 1.369–2.884), lymphatic invasion (OR = 4.389; 95% CI 1.522–12.658), perineural invasion (OR = 6.545; 95% CI 1.262–33.948), and minimal ETE (OR = 1.852; 95% CI 1.298–2.643) were found to be independent risk factors of LN metastasis. Conclusions Minimal ETE is associated with LN metastasis in single PTMC, compared to no ETE. Minimal ETE should be considered in the management of patients with single PTMC, whether surgical or during active surveillance.

Abstract Background The study was aimed at investigating the potential role of chronic lymphocytic thyroiditis (CLT) in papillary thyroid cancer (PTC) aggressiveness for patients aged below 55, as well as to figure out factors influencing potential recurrence risk in different age groups. Methods A total of 635 adult patients were retrospectively analyzed. 188 patients were diagnosed with coexistent CLT and the remaining 447 were classified as non-CLT. Then the characteristics of CLT-coexisted patients and non-CLT ones were compared respectively when patients were aged ≥ 55 years or below. The association among postoperative clinicopathological features were also analyzed using multivariate regression. In addition, the prognostic value of several variables relating to high-risk recurrence were estimated within different age groups. Results When divided in two age groups (55 years as the borderline), non-CLT group (aged below 55 years) had a remarkable frequency of small size lesion (Dmax ≤ 1 cm) compared with CLT-coexisted patients (54.6% to 43.0%, p = 0.02). In addition, non-CLT patients tended to have intrathyroidal extension as opposed to those with coexistent CLT (20.2% to 28.2%, p = 0.05). In multivariate analysis, CLT still significantly acted as an independent risk factor of greater lesion size (Dmin > 1 cm) (OR = 1.7, p = 0.02) and mildly promoted gross extrathyroidal extension (ETE) (OR = 1.4, p = 0.06). However, associations didn’t emerge in the characteristics mentioned above with CLT when patients were ≥ 55 years old. The prognostic value of CLT in high-risk recurrence was evident only in patients aged 35–44 years. (OR = 2.4, 95%CI:1.2–5.4, p = 0.02). Greater lesion size independently promoted gross ETE, no matter patients were aged above 55 years or not. Its prognostic value of high-risk recurrence was significant throughout all age groups. Conclusion These findings revealed that CLT coexistence might be the unfavorable factor of PTC aggressiveness in patients aged below 55 years. Its role as well as greater tumor size may potentially predict higher recurrence risk according to results figured out in the prediction model.

Zhi Li,1 Shuqiang Chen,2 Jinguo Li3 1Health Management Center, The Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Fuzhou, Fujian, People’s Republic of China; 2Ultrasound Department, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Ultrasound Department, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Jinguo Li, Email Lxy1990@163.comBackground: Extrathyroidal extension (ETE) is a crucial factor affecting the prognosis of thyroid cancer. Two-dimensional ultrasound is highly sensitive to ETE, but the sensitivity and specificity for severe ETE are unideal, so it does not improve the prognosis.Materials and Methods: This retrospective study evaluated patients within three years of subcapsular thyroid cancer diagnosis with fine-needle aspiration (FNA). Routine ultrasound was performed and examined before surgery. In addition to the traditional two-dimensional assessment method, particular attention was paid to transcapsular blood vessels, and the diagnostic efficacy of the two methods for mild, severe, and anterior and posterior ETE was compared.Results: A total of 208 thyroid cancer nodules were included. Tumor size and gender were correlated with whether ETE occurred. The general method is more accurate for the overall identification of ETE but is not specific enough for severe ETE, while the transvascular method is the opposite. The two are similar in identifying the ETE of the anterior capsule, but the transvascular method has higher specificity in identifying the ETE of the posterior capsule.Conclusion: The traditional two-dimensional method is highly sensitive to ETE detection in the anterior capsule, while transcapsular blood flow can more effectively detect extensive ETE and ETE in the posterior capsule.Keywords: extrathyroidal extension, thyroid cancer, ultrasound, prognosis, metastasis

BACKGROUND: Extrathyroidal extension (ETE) significantly affects the treatment strategy for thyroid cancer. We present a new method to predict ETE of papillary thyroid carcinoma (PTC). METHODS: We enrolled 1 481 patients with PTCs. The ETE was classified into minimal and gross ETE. Using the novel "contact angle of the tumor on sonography" (CATS) system, we calculated optimal cutoffs for predicting ETE according to tumor location and compared the diagnostic performance to that of previous methods. RESULTS: The optimal cutoff angles for predicting anterior minimal and gross ETE were 41.5° and 49.4°, respectively, while those for posterior ETE were 39.8° and 54.6°, respectively. The optimal cutoff angle predicting tracheal ETE was 88.0°. The diagnostic performance was comparable to that of previous methods. CONCLUSION: The CATS method for predicting ETE is a valuable alternative. [ABSTRACT FROM AUTHOR]

Extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) is an indication of disease progression and can influence treatment aggressiveness. This meta-analysis assesses the diagnostic accuracy of ultrasonography (US) in detecting ETE. A systematic review and meta-analysis were performed by searching PubMed, Embase, and Cochrane for studies published up to April 2022. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. The areas under the curve (AUC) for summary receiver operating curves were compared. A total of 11 studies analyzed ETE in 3795 patients with PTC. The sensitivity of ETE detection was 76% (95%CI = 74–78%). The specificity of ETE detection was 51% (95%CI = 49–54%). The DOR of detecting ETE by US was 5.32 (95%CI = 2.54–11.14). The AUC of ETE detection was determined to be 0.6874 ± 0.0841. We report an up-to-date analysis elucidating the diagnostic accuracy of ETE detection by US. Our work suggests the diagnostic accuracy of US in detecting ETE is adequate. Considering the importance of ETE detection on preoperative assessment, ancillary studies such as adjunct imaging studies and genetic testing should be considered. [ABSTRACT FROM AUTHOR]

Medullary thyroid carcinoma (MTC) accounts for only 2–5% of all thyroid malignancies. Clinical and pathological characteristics alone may suffice to predict outcomes, but unstable behavior in some cases suggests that other factors may influence a worse course of the disease. This study aims to identify criteria that could predict increased aggressiveness. We analyzed 59 consecutive MTC cases. We focused on the relationships among clinicopathological characteristics, parameters of aggressiveness (extrathyroidal extension, lymphovascular invasion, and lymph node metastasis), and parameters for MTC grading. Statistically significant correlations were found for tumor size, lymphovascular invasion, and lymph node metastasis and tumor focality and lymph node metastasis. Our results showed, in tumors larger than 40 mm, odds ratios (ODs) of 13.695 and 6 for lymphovascular invasion and lymph node metastasis, respectively; in multifocal tumors, we registered an OD of 9.42 for lymph node metastasis. No significant correlation was found for the parameters of the MTC grading system when assessed individually and integrated by reporting low-grade and high-grade risk groups. Although our data indicate that lymphovascular invasion and lymph node metastasis remain significant markers for aggressiveness, studies on larger series of cases are mandatory to detect and validate new factors responsible for the variable course of MTC. [ABSTRACT FROM AUTHOR]

Objectives: The presence of extrathyroidal extension (ETE) in patients with differentiated thyroid cancer (DTC) serves as a significant prognostic indicator. Consequently, the staging of DTC is categorized into extensive ETE and gross ETE that solely impacts the strap muscles (gross strap muscle invasion [gSMI]). However, there is a lack of sufficient evidence concerning the relationship between gSMI and prognosis, particularly in terms of tumor size., Methods: Relevant literature was searched in Medline, Embase, Cochrane Library, and KoreaMed. All procedures were conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and carried out by two independent reviewers. The meta-analysis utilized a random-effects model to account for the diversity of the studies. Risk of Bias for Nonrandomized Studies (RoBANS) version 2.0, an evaluation tool for non-randomized studies, was employed to assess the quality of the selected research. Clinical data from observational studies that examined the relationship between the degree of ETE and prognosis were gathered, and a meta-analysis was conducted., Results: Eighteen observational studies were included in this analysis. Subgroup analyses were conducted for each outcome. The findings revealed that the recurrence rate (odds ratio [OR], 2.498), disease-specific mortality (risk ratio [RR], 2.984), overall mortality (RR, 1.361), and lymph node (LN) metastasis (OR, 5.355) were significantly higher in patients with gSMI than in those without ETE. However, when the analysis was restricted to tumors measuring 4 cm or smaller, no significant differences in prognostic outcomes were observed, with the exception of LN metastasis., Conclusion: gSMI negatively impacts prognosis; however, this correlation diminishes with smaller tumor sizes. Thus, a more cautious approach is warranted during the treatment process.

Background: Papillary thyroid carcinoma (PTC) is the most commonly diagnosed differentiated thyroid carcinoma. There is controversy about performing upfront lobectomy vs thyroidectomy for smaller well differentiated thyroid carcinoma. Methods: A retrospective study from 2015 to 2020 was conducted consisting of consecutive patients with a preoperative malignant (Bethesda VI) cytology on fine needle aspirate (FNA) consistent with PTC. Specific ultrasonographic features such as taller than wide, hypoechogenicity, irregular margins, internal vascularity and microcalcifications were recorded. Criteria for exclusion was the presence of positive lymph nodes, extrathyroidal extension, familial thyroid carcinoma and bilateral disease detected preoperatively. Outcome was defined as a lobectomy being adequate treatment or a completion thyroidectomy recommended based on current 2015 ATA guidelines. Results: Preoperative malignant cytological nodules (Bethesda VI) with irregular margins on sonography were significantly (p = 0.025) at increased risk (OR = 2.48) of requiring a completion thyroidectomy. There was also no statistically significant difference between groups when stratified by size with 50% of tumours between 1 and 2 cm requiring a completion thyroidectomy. Conclusions: The presence of irregular margins on ultrasound predicts an increased risk of requiring a completion thyroidectomy. Specific consideration of this sonographic finding should be made when counselling patients who have cytologically confirmed papillary thyroid carcinoma regarding the best choice of thyroid operation.

Introduction: Differentiated thyroid carcinoma usually has a good prognosis. Primary treatment is surgery, followed by radioactive iodine ablation based on risk stratification. The incidence of local and distant recurrence is 30%. Recurrence can be managed surgically or with multiple cycles of radioactive iodine ablation. There are multiple risk factors for structural disease recurrence proposed by the American Thyroid Association. In this study, we attempted to study the risk factors of structural recurrence in differentiated carcinoma thyroid and the pattern of recurrence in patients with node negative thyroid cancer who underwent total thyroidectomy. Methodology: This study selected a retrospective cohort of 1498 patients with differentiated thyroid cancer: out of these, 137 patients who presented after thyroidectomy with cervical nodal recurrence from January 2017 to December 2020 were included. The risk factors for central and lateral lymph node metastasis were analysed by univariate and multivariate analyses, including age, gender, T-stage, extrathyroidal extension, multifocality and high-risk variants. In addition, the presence of TERT/BRAF mutations was studied as a risk factor for central and lateral nodal recurrence. Results: Out of 1498 patients, 137 who fit the inclusion criteria were analysed. Majority were female (73%); mean age was 43.1 years. Lateral compartment neck nodal recurrence was more common (84%), while isolated central compartment nodal recurrence occurred only in 16%. Most recurrences were seen in the first 1 year (23.3%) or after 10 years post-total thyroidectomy (35.7%). On univariate variate analysis, multifocality, extrathyroidal extension and high-risk variants stage were significant factors for nodal recurrence. However, on multivariate analysis for lateral compartment recurrence, multifocality, extrathyroidal extension and age were found to be significant. On multivariate analysis, multifocality, extrathyroidal extension and presence of high-risk variants were significant predictors of central compartment nodal metastasis. ROC curve analysis showed AUC for ETE (AUC-0.795), multifocality (AUC-0.860), presence of high-risk variants (AUC-0.727) and T-stage (AUC-0.771) as sensitive predictive factors for central compartment. 69 percent patients with very early recurrences (

Aim. To evaluate the diagnostic performance of radiomics features of two-dimensional (2D) and three-dimensional (3D) ultrasound (US) in predicting extrathyroidal extension (ETE) status in papillary thyroid carcinoma (PTC). Patients and Methods. 2D and 3D thyroid ultrasound images of 72 PTC patients confirmed by pathology were retrospectively analyzed. The patients were assigned to ETE and non-ETE. The regions of interest (ROIs) were obtained manually. From these images, a larger number of radiomic features were automatically extracted. Lastly, the diagnostic abilities of the radiomics models and a radiologist were evaluated using receiver operating characteristic (ROC) analysis. We extracted 1693 texture features firstly. Results. The area under the ROC curve (AUC) of the radiologist was 0.65. For 2D US, the mean AUC of the three classifiers separately were: 0.744 for logistic regression (LR), 0.694 for multilayer perceptron (MLP), 0.733 for support vector machines (SVM). For 3D US they were 0.876 for LR, 0.825 for MLP, 0.867 for SVM. The diagnostic efficiency of the radiomics was better than radiologist. The LR model had favorable discriminate performance with higher area under the curve. Conclusion. Radiomics based on US image had the potential to preoperatively predict ETE. Radiomics based on 3D US images presented more advantages over radiomics based on 2D US images and radiologist. [ABSTRACT FROM AUTHOR]

Simple Summary: In the 8th edition of the AJCC/UICC TNM staging system, T3b is defined as gross extrathyroidal extension (gETE) invading only the strap muscles from a tumor of any size. However, defining T3b according to tumor size remains controversial. We created new T3b categories according to tumor size (T3b-1, tumor ≤ 2 cm in T3b; T3b-2, 2 cm < tumor ≤ 4 cm in T3b). There was a significant difference only in T3b-2 compared to T2. Novel methods of evaluating the effect of gETE according to tumor size should be considered in further revisions of the AJCC/UICC TNM staging system. The purpose of the present study was to compare the risk of recurrence between T2 and T3b papillary thyroid carcinoma (PTC) and the effect of tumor size on survival in T3b disease. A total of 634 patients with PTC who underwent thyroid surgery at a single center were retrospectively analyzed. Clinicopathological characteristics were compared according to the T category in the TNM staging system, with T3b divided into T3b-1 (tumor size, ≤2 cm) and T3b-2 (tumor size, 2–4 cm). Disease-free survival (DFS) and recurrence risk were compared between T2, T3b, T3b-1, and T3b-2. Tumor size was significantly larger in T2 than in T3b. A significant difference in recurrence was observed between T2 and T3b-2 but not between T2 and T3b-1. T3b-2 was identified as a significant risk factor for PTC recurrence. A significant difference in the DFS curve was observed between T2 and T3b-2. However, no significant differences in survival were observed between T2 and T3b or T3b-1. These results indicate that the prognostic impact of T3b may vary depending on tumor size. Further studies are required to determine the need for T classifications that account for tumor size and gETE invasion of the strap muscles. [ABSTRACT FROM AUTHOR]

Detection of extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) influences treatment plan and surgical aggressiveness. Ultrasound (US) is the long-standing preoperative imaging method of choice. Recent literature from Asia suggests US accuracy to be influenced by patient characteristics, such as body mass index (BMI). Here, we examine the effect of BMI on the accuracy of US at a North American tertiary referral center. A total of 204 PTC-confirmed patients were retrospectively read by a radiologist blinded to surgical pathology findings. The radiologist recorded multiple sonographic features, including ETE, loss of echogenic capsule, nodule vascularity, capsular abutment, and bulging of contour. When considering all patients, the ultrasonographic feature with the best overall performance was loss of echogenic capsule (diagnostic odds ratio (DOR) = 4.48, 95% confidence interval (CI) = 1.86–10.78). Sub-group analysis by patient BMI found that area under the curve (AUC) for sonographic features was greater in non-obese BMI patients (0.71 ± 0.06) when compared with obese patients (0.43 ± 0.05; p = 0.001). Overall, US diagnostic performance was significantly better in non-obese (DOR = 3.70, 95%CI = 1.53–8.94) patients when compared to those who were obese (DOR = 1.12, 95%CI = 0.62–2.03; p = 0.03). Loss of the echogenic capsule did not differ between the two cohorts with respect to DOR (p = 0.51), specificity (p = 0.52), or sensitivity (p = 0.09). Our work suggests that the diagnostic value of ETE detection by US is impaired in obese patients. Considering that loss of the echogenic capsule did not differ with respect to diagnostic performance, specificity, nor sensitivity between non-obese and obese patients, it could be considered the most important predictor of US-determined ETE. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine sonographic features and clinical significance of minor extrathyroidal extension (ETE) to the posterior thyroid capsule in papillary thyroid microcarcinoma (PTMC) patients. Methods: We retrospectively reviewed the records of 506 PTMC patients consisting of 151 patients with minor ETE and 355 patients without ETE. Significant clinicoradiologic features associated with ETE were identified by logistic regression analyses. The diagnostic performance of sonographic features, including the presence of capsular abutment, capsular abutment degree (< 25%, 25–50%, ≥ 50%), and protrusion, were assessed for the diagnosis of posterior minor ETE. Interobserver agreement was calculated. Results: PTMC patients with posterior minor ETE were more likely to have lymphovascular invasion and lateral neck lymph node metastasis (OR = 2.636, 95%CI: 1.754, 3.963 and OR = 2.897, 95%CI: 1.069, 7.848). Regarding the diagnostic performance, the capsular abutment yielded the highest sensitivity (81.5%), followed by ≥ 25% abutment, protrusion, and ≥ 50% abutment (57.0%, 21.9%, and 4.6%, respectively), with similar levels of diagnostic accuracy (71.3–75.1%). The specificity was highest for the sonographic feature of ≥ 50% abutment (99.7%), followed by protrusion, ≥ 25% abutment, and capsular abutment (97.8%, 82.0%, and 68.7%, respectively). Abutment assessment had a moderate interobserver agreement (K = 0.705), and abutment degree and protrusion assessment had a fair and slight interobserver agreement (K = 0.553 and 0.287). Conclusions: Sonographic features of posterior capsular abutment are sensitive and reliable for diagnosis of posterior minor ETE and are associated with lymphovascular invasion and lateral neck lymph node metastasis in PTMC patients. The assessment of posterior minor ETE is important for considering candidates for active surveillance among PTMC patients. Key Points: • PTMC patients with posterior minor ETE were more likely to have lymphovascular invasion and lateral neck lymph node metastasis. • Sonographic features of posterior capsular abutment are sensitive and reliable for the diagnosis of posterior minor ETE. • The assessment of posterior minor ETE is important for considering candidates for active surveillance among PTMC patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Whether multifocal papillary thyroid carcinoma (PTC) is more associated with recurrence than unifocal PTC is controversial. This study investigates the appropriateness of lobectomy for patients with preoperatively detected unilateral multifocal PTC. Methods: This study retrospectively analyzed 198 patients with unilateral multifocal PTC at the Asan Medical Center between 2000 and 2005. Clinicopathological features and locoregional recurrence rates were compared according to operation type (lobectomy, n = 62; total thyroidectomy (TT), n = 136). Results: The lateral neck lymph node area was the most frequent recurrence site. Univariate analyses showed that gross extrathyroidal extension (ETE), bilateral multifocal malignancy diagnosed after operation (bilaterality), lymph node (LN) metastasis, lymphovascular invasion, tumor size (≥2 vs

Liguang Zhou,1 Gang Chen,2 Lei Sheng,3 Nan Liu,3 Bin Zhang,3 Qingdong Zeng,3 Bo Chen3 1Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of General Surgery, Shandong Guoxin Healthcare Group Xinwen Center Hospital, Taian, People’s Republic of China; 3Department of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of ChinaCorrespondence: Bo ChenDepartment of Thyroid Surgery, General Surgery, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan, 250012, People’s Republic of ChinaTel + 86-531-82165383Email chenbo_780721@hotmail.comPurpose: To analyze the effect of Hashimoto’s thyroiditis (HT) concurrent with papillary thyroid cancer (PTC) on cervical lymph node metastasis (LNM).Methods: Two thousand nine hundred twenty-six patients who underwent thyroidectomy and lymph node dissection between January 2015 and December 2018 were enrolled in this study. Patient demographics and clinicopathologic features were analyzed.Results: Of the total enrolled patients, 598 (20.4%) had concurrent HT. There were 1482 PTC cases with N0, 1033 cases with N1a, and 411 cases with N1b. Patients with HT had lower frequency of extrathyroidal extension (ETE), lymphatic vascular (LV) invasion, high pathological T stage (III+IV) and central LNM rate. Stratifying central LNM by non-ETE or without intrathyroidal spreading, it was further found that central LNM rate in patients with HT was lower than that of patients without HT. However, there was no significant difference in the central LNM rate in patients with PTC stratified by ETE or intrathyroidal spreading. HT with PTC played a weak protective role in N1a, reducing the risk of N1a by 16.4%. Conversely, HT is a risk factor for N1b, increasing the risk by 1.336 times compared to patients without HT. TgAb is an independent risk factor for N1b, which appears related to the promotion of N1b by HT.Conclusion: In PTC, HT has a protective effect on central LNM and a risk effect on lateral LNM, although the difference was not significant. This weak protective effect on N1a is more obvious in PTC with less aggressive clinicopathologic characteristics. The risk effect of HT on N1b may be associated with TgAb.Keywords: Hashimoto’s thyroiditis, papillary thyroid cancer, lymph node metastasis, influence factor, extrathyroidal extension, intrathyroidal spreading

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. PTC patients with extrathyroidal extension (ETE) are associated with poor prognoses. The preoperative accurate prediction of ETE is crucial for helping the surgeon decide on the surgical plan. This study aimed to establish a novel clinical-radiomics nomogram based on B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) for the prediction of ETE in PTC. A total of 216 patients with PTC between January 2018 and June 2020 were collected and divided into the training set (n = 152) and the validation set (n = 64). The least absolute shrinkage and selection operator (LASSO) algorithm was applied for radiomics feature selection. Univariate analysis was performed to find clinical risk factors for predicting ETE. The BMUS Radscore, CEUS Radscore, clinical model, and clinical-radiomics model were established using multivariate backward stepwise logistic regression (LR) based on BMUS radiomics features, CEUS radiomics features, clinical risk factors, and the combination of those features, respectively. The diagnostic efficacy of the models was assessed using receiver operating characteristic (ROC) curves and the DeLong test. The model with the best performance was then selected to develop a nomogram. The results show that the clinical-radiomics model, which is constructed by age, CEUS-reported ETE, BMUS Radscore, and CEUS Radscore, showed the best diagnostic efficiency in both the training set (AUC = 0.843) and validation set (AUC = 0.792). Moreover, a clinical-radiomics nomogram was established for easier clinical practices. The Hosmer–Lemeshow test and the calibration curves demonstrated satisfactory calibration. The decision curve analysis (DCA) showed that the clinical-radiomics nomogram had substantial clinical benefits. The clinical-radiomics nomogram constructed from the dual-modal ultrasound can be exploited as a promising tool for the pre-operative prediction of ETE in PTC.

Background: Differentiated thyroid cancer has excellent overall survival. However, around 20% of patients experience recurrent diseases after a certain time of follow-up. Therefore, identification of risk factors for recurrence is necessary to adjust treatment and surveillance planning. Methods: A retrospective study was conducted of 312 patients with differentiated thyroid cancer who received surgery with and without adjuvant treatment. Clinical and pathological risk factors were analyzed for recurrences. Results: After median follow-up of 57 months, 109 of 312 patients (34.9%) developed recurrences. Extrathyroidal extension and positive cervical nodes were significantly associated with recurrences (OR = 2.449, 95%CI:1.260–4.760, P = 0.008 and OR = 3.511, 95%CI:1.860–6.626, P < 0.001; respectively). Lympho-vascular invasion (LVI) and tumor multifocality were also associated with increased risk of recurrence (OR = 2.577, 95%CI:1.380–4.812, P = 0.003 and OR = 1.602, 95%CI:1.001–2.495, P = 0.050; respectively). Using multivariable regression, only older age and tumor infiltration to the lymph nodes were significantly associated with recurrences (OR = 2.227, 95%CI:1.037–4.782, P = 0.040 and OR = 2.966, 95%CI:1.470–5.986, P = 0.002; respectively). In addition, T4, cervical lymph node infiltration, older age, and LVI were associated with shorter recurrence-free survival. Conclusion: Recurrence rates in our study population are relatively high. Extrathyroidal extension, positive neck lymph node, and older age were associated with recurrence risks of well differentiated thyroid cancers. [ABSTRACT FROM AUTHOR]

Objective: The right cervical central lymph nodes include lymph nodes anterior to the right recurrent laryngeal nerve (LN-arRLN) and lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN), and are separated by the right recurrent laryngeal nerve (RLN). LN-prRLN is a common site of nodal recurrence after the resection of papillary thyroid carcinoma (PTC). However, the complexity in anatomical structure brings difficulties in determining the surgical scope, so it is necessary to assess the pattern and predictive factors of right cervical central lymph nodes, especially LN-prRLN metastasis in papillary thyroid carcinoma. Methods: A total of 562 diagnosed PTC patients who underwent right or total thyroidectomy were enrolled in this retrospective study. The clinicopathological features were collected, univariate and multivariate analyses were performed to determine predictive factors of the right central lymph node metastasis. Results: In this study, the metastatic rates of the right CLN, the LN-arRLN and the LNprRLN were 59.6% (335/562), 51.8% (291/562) and 30.4% (171/562), respectively. And 22.6% (127/562) of patients had both LN-arRLN and LN-prRLN metastasis. Among patients without LN-arRLN metastasis, the rate of LN-prRLN metastasis was 16.2% (44/271), accounting for 25.7% of the LN-prRLN metastasis group. Factors associated with an increased risk of LN-arRLN metastasis include male, age below 55 years, tumor size > 1cm, extrathyroidal extension (ETE), clinical lymph nodes metastasis(cN1), lateral lymph node metastasis, and left CLN metastasis. In addition, ETE, lateral lymph node metastasis, and LN-arRLN metastasis were independent factors of LN-prRLN metastasis. The predictive factors of LN-prRLN in cN0 PTC were further explored, revealing that tumor size =1.5cm, ETE, and LN-arRLN metastasis were independent predictors of LN-prRLN metastasis in cN0 PTC. Conclusion: The LN-prRLN should not be ignored in surgery because of its high rate of metastasis. Our findings indicate that thorough dissection of central lymph nodes, especially LN-prRLN is crucial in clinical work. [ABSTRACT FROM AUTHOR]

Prognostic factors for excellent response (ER) to initial therapy in patients with papillary thyroid cancer (PTC) have not been determined. In this study, we investigated the response to initial therapy in PTC patients and independent prognostic factors for ER in a prospective multicenter study in China. A total of 506 PTC patients from nine centers in China were enrolled in this study, all of whom underwent total or near total thyroidectomy with lymph node dissection and subsequent radioiodine therapy. Univariate and multivariable logistic regression analyses were carried out to determine the independent prognostic factors for ER. The optimal cutoff value of the number of metastatic lymph nodes for predicting ER was determined by the receiver operating characteristic curve. A total of 139 patients (27.5%) achieved ER after initial therapy. Extrathyroidal extension, the number of metastatic lymph nodes, and preablative-stimulated thyroglobulin (Ps-Tg) were independent risk factors for ER for the entire population. In a subgroup analysis, extrathyroidal extension and Ps-Tg were independent risk factors for ER in pathological N1a patients, while the number of metastatic lymph nodes and Ps-Tg were independent risk factors for ER in pathological N1b patients. The appropriate cutoff values of the number of metastatic lymph nodes in predicting ER were 5 and 13 for the entire population and pathological N1b PTC patients, respectively. PTC patients with more metastatic lymph nodes were more likely to fail to achieve ER. Extrathyroidal extension, the number of metastatic lymph nodes, and Ps-Tg were important prognostic factors for ER after initial therapy in PTC patients. [ABSTRACT FROM AUTHOR]

Background: Extrathyroidal extension (ETE) is considered a major prognostic factor in papillary thyroid carcinoma (PTC). Patients with gross ETE are at increased risk of recurrence and mortality. The importance of minimal ETE still remains controversial, especially in patients with papillary thyroid microcarcinoma (PTMC). The purpose of this study was to evaluate the association between ETE and lymph node (LN) metastasis in single PTMC. Methods: A retrospective analysis was performed of 1994 patients underwent thyroidectomy for PTC between 2012 and 2016 in a single institution. Patients with combined thyroid carcinoma of other types and those who underwent completion thyroidectomy were excluded. After further exclusion of PTC larger than 1 cm and multifocal tumors, 814 patients with single PTMC were included in the study. Results: 72.9% patients had no ETE, 25.1% minimal ETE, and 2.1% gross ETE. ETE was associated with lymphatic invasion, perineural invasion, and vascular invasion. Patients with minimal and gross ETE were also more likely to have LN metastasis, including lateral neck metastasis, compared to those without ETE. In univariate analysis, LN metastasis was associated with male gender, conventional PTC, lymphatic invasion, perineural invasion, and ETE. In multivariate analysis, male gender (OR = 1.987; 95% CI 1.369–2.884), lymphatic invasion (OR = 4.389; 95% CI 1.522–12.658), perineural invasion (OR = 6.545; 95% CI 1.262–33.948), and minimal ETE (OR = 1.852; 95% CI 1.298–2.643) were found to be independent risk factors of LN metastasis. Conclusions: Minimal ETE is associated with LN metastasis in single PTMC, compared to no ETE. Minimal ETE should be considered in the management of patients with single PTMC, whether surgical or during active surveillance. [ABSTRACT FROM AUTHOR]

Simple Summary: In papillary thyroid carcinoma (PTC), staging classification of gross and minimal extrathyroidal extension (ETE) has been recently modified in the eighth edition of the American Joint Commission on Cancer/Union for International Cancer Control (AJCC/UICC) TNM staging system. In this study, we compared the clinicopathological characteristics and recurrence rates between minimal and gross ETE. No significant differences in the recurrence and disease-free survival rates were found between the two groups. Whether gross ETE invading strap muscles (T3b) only could be a risk factor for recurrence in PTC remains questionable. The presence of extrathyroidal extension (ETE) is associated with locoregional recurrence and distant metastases in papillary thyroid carcinoma (PTC). This study was designed to compare the recurrence risk between minimal ETE (mETE) and gross ETE (gETE) in patients with PTC using propensity score matching. In this study, 4452 patients with PTC who underwent thyroid surgery in a single center were retrospectively analyzed, and clinicopathological characteristics were compared according to the ETE status. Disease-free survival (DFS) and recurrence risk were compared between mETE and gETE after propensity score matching. The mean follow-up duration was 122.7 ± 22.5 months. In multivariate analysis, both mETE and gETE were not associated with recurrence risk before propensity score matching (p = 0.154 and p = 0.072, respectively). After propensity score matching, no significant difference in recurrence rates was observed between the two groups (p = 0.668). DFS of the gETE group did not significantly differ from that of the mETE group (log-rank p = 0.531). This study revealed that both mETE and gETE are not independent risk factors for the risk of recurrence in PTC. Our findings suggest that gETE invading strap muscles only might not be associated with worse oncological outcomes in PTC. [ABSTRACT FROM AUTHOR]

Abstract Background To determine the predictive capability of MRI-based radiomics for extrathyroidal extension detection in papillary thyroid cancer (PTC) pre-surgically. Methods The present retrospective trial assessed individuals with thyroid nodules examined by multiparametric MRI and subsequently administered thyroid surgery. Diagnosis and extrathyroidal extension (ETE) feature of PTC were based on pathological assessment. The thyroid tumors underwent manual segmentation, for radiomic feature extraction. Participants were randomized to the training and testing cohorts, at a ratio of 7:3. The mRMR (maximum correlation minimum redundancy) algorithm and the least absolute shrinkage and selection operator were utilized for radiomics feature selection. Then, a radiomics predictive model was generated via a linear combination of the features. The model’s performance in distinguishing the ETE feature of PTC was assessed by analyzing the receiver operating characteristic curve. Results Totally 132 patients were assessed in this study, including 92 and 40 in the training and test cohorts, respectively). Next, the 16 top-performing features, including 4, 7 and 5 from diffusion weighted (DWI), T2-weighted (T2 WI), and contrast-enhanced T1-weighted (CE-T1WI) images, respectively, were finally retained to construct the radiomics signature. There were 8 RLM, 5 CM, 2 shape, and 1 SZM features. The radiomics prediction model achieved AUCs of 0.96 and 0.87 in the training and testing sets, respectively. Conclusions Our study indicated that MRI radiomics approach had the potential to stratify patients based on ETE in PTCs preoperatively.