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The study was to evaluate the effect of radioactive iodine (RAI) treatment application time and clinical, histopathological factors on ablation success in patients with operated papillary thyroid cancer (PTC) in low and intermediate-risk. One hundred sixty-one patients with PTC in the low and intermediate-risk were evaluated. Most patients (89.4%) were in the low-risk, and 10.6% were in the intermediate-risk. When the patients were divided into two groups according to the date of receiving RAI treatment after surgery, those who received early treatment (≤3 months) constituted the majority of the patients (72.7%). Seventeen patients received 1.85 Gigabecquerel (GBq), 119 3.7 GBq, 25 5.55 GBq RAI. Most patients (82%) achieved ablation success after the first RAI treatment. The time interval between surgery and RAI treatment did not affect ablation success. Stimulated Tg level measured on the RAI treatment day was an independent predictive factor for successful ablation (p<0.001). The cut-off value of Tg found to predict ablation failure was 5.86 ng/ml. It was concluded that 5.55 GBq RAI treatment could predict ablation success compared to 1.85 GBq dose (p=0.017). It was concluded that having a T1 tumor may predict treatment success compared to a T2 or T3 tumor (p=0.001, p<0.001, retrospectively). The time interval does not affect ablation success in low and intermediate-risk PTC. The ablation success rate may decrease in patients who receive low-dose RAI and have high Tg levels before treatment. The most crucial factor in achieving ablation success is giving enough doses of RAI to ablate the residual tissue. [ABSTRACT FROM AUTHOR]

Objectives: To develop an artificial intelligence (AI) system for predicting cervical lymph node metastasis (CLNM) preoperatively in patients with papillary thyroid cancer (PTC) based on CT images. Methods: This multicenter retrospective study included the preoperative CT of PTC patients who were divided into the development, internal, and external test sets. The region of interest of the primary tumor was outlined manually on the CT images by a radiologist who has eight years of experience. With the use of the CT images and lesions masks, the deep learning (DL) signature was developed by the DenseNet combined with convolutional block attention module. One-way analysis of variance and least absolute shrinkage and selection operator were used to select features, and a support vector machine was used to construct the radiomics signature. Random forest was used to combine the DL, radiomics, and clinical signature to perform the final prediction. The receiver operating characteristic curve, sensitivity, specificity, and accuracy were used by two radiologists (R1 and R2) to evaluate and compare the AI system. Results: For the internal and external test set, the AI system achieved excellent performance with AUCs of 0.84 and 0.81, higher than the DL (p =.03,.82), radiomics (p <.001,.04), and clinical model (p <.001,.006). With the aid of the AI system, the specificities of radiologists were improved by 9% and 15% for R1 and 13% and 9% for R2, respectively. Conclusions: The AI system can help predict CLNM in patients with PTC, and the radiologists' performance improved with AI assistance. Clinical relevance statement: This study developed an AI system for preoperative prediction of CLNM in PTC patients based on CT images, and the radiologists' performance improved with AI assistance, which could improve the effectiveness of individual clinical decision-making. Key Points: • This multicenter retrospective study showed that the preoperative CT image-based AI system has the potential for predicting the CLNM of PTC. • The AI system was superior to the radiomics and clinical model in predicting the CLNM of PTC. • The radiologists' diagnostic performance improved when they received the AI system assistance. [ABSTRACT FROM AUTHOR]

Background. Due to the low sensitivity and specificity of neck ultrasound in the evaluation of the central lymph nodes, it is necessary to find alternative ways to predict central lymph node metastases in patients with papillary thyroid cancer (PTC). The purpose of the study is to develop a prognostic model for assessing the risk of local metastasis of papillary thyroid cancer based on preoperative ultrasound and demographic predictors. Materials and methods. A retrospective monocenter cohort study was conducted. The data of 401 patients who underwent surgery for PTC were processed. The main group included 179 patients in whom central lymph node metastases were detected during histopathological examination. The comparison group consisted of 222 patients without metastases according to the results of histopathological examination. When conducting the analysis, the following signs were considered as risk factors: subcapsular location of the tumor; size; blurred boundaries; the presence of calcification areas (microcalcifications); age of a patient. Inclusion criteria: PTC that was cytologically confirmed at the preoperative stage; surgeries (thyroidectomy/hemithyroidectomy and central neck lymph node dissection). Exclusion criteria: history of neck surgery; multifocal lesions of the thyroid gland. Results. The following logistic equation was obtained using the StatPlus program: y = –1.839 – 0.037 × X1 + 0.097 × X2 + 1.123 × X3 + 1.198 × X4 + + 0.692 × X5, where X1, X2, X3, X4, X5 are age (years), size (mm), subcapsular location (presence), blurred boundaries (presence), calcifications (presence), respectively. The obtained prognostic model provided the following operational characteristics when specifying the threshold value for P, which is equal to 0.44 (the decisive rule X > T): sensitivity — 75.4 %, specificity — 79.3 %, diagnostic efficiency — 75.1 %. To assess the quality of the model, the receiver operator characteristic (ROC) analysis was performed. The following data were obtained: area under the ROC curve = 0.797 (95% confidence interval: 0.753–0.841), which corresponds to the good quality of the model, and Youden index J = 0.5155. Checking the quality of the model on a control group of 100 people gave the following results: sensitivity — 72.2 %, specificity — 76.1 %, diagnostic efficiency — 75.8 %. Conclusions. The application of a prognostic model based on ultrasound data and the patient’s age makes it possible to predict the presence of local metastases of the PTC at the preoperative stage with a diagnostic efficiency of 75.8 %. No prognostic model gives 100% prediction accuracy. When choosing the treatment, additional influencing factors (history of radiation exposure, burdened family history, etc.) for a specific patient should be considered. [ABSTRACT FROM AUTHOR]

Objectives: Unilateral or bilateral prophylactic central neck dissection (CND) in papillary thyroid cancer (PTC) is still controversial. We aimed to evaluate the risk factors for contralateral paratracheal lymph node metastasis and whether CND might be performed unilaterally. Methods: Prospectively collected data of patients who underwent bilateral CND and lateral neck dissection (LND) with thyroidectomy due to PTC with lateral metastases, between January 2012 and November 2019, were evaluated retrospectively. The patients were divided into two groups according to the presence (Group 1) and absence (Group 2) of metastasis in the contralateral paratracheal region. A total of 42 patients (46 ±15.7 years) were operated. In the contralateral paratracheal region, Group 1 (35.7%) had metastases, while Group 2 (64.3%) had no metastases. In groups 1 and 2, metastasis rates were 100% vs 77.8% (p=0.073), 46.7% vs 18.5% (p=0.078), and 80% vs 40.7% (p=0.023) for the ipsilateral paratracheal, prelaryngeal and pretracheal lymph nodes, respectively. The number of metastatic lymph nodes in the central region was significantly higher in Group 1 compared to Group 2 as; 10.7±8.4 vs. 2.6±2.4 (p=0.001) in bilateral central region material; 8.3±7.4 vs. 2.9±2.7 (p=0.001) in lateral metastasis with ipsilateral unilateral central region; 3.8±3.4 vs. 1.9±1.9 (p=0.023) in ipsilateral paratracheal area; and 3.7±4.6 vs. 0.6±0.9 (p=0.001) in pretracheal region, respectively. However, no significant difference was found regarding the prelaryngeal region material (0.9±1.8 vs. 0.2±0.4 (p=0.71)). Results: >2 metastatic central lymph nodes in unilateral CND material (AUC: 0.814, p<0.001, J=0.563) can estimate contralateral paratracheal metastasis with 93% sensitivity, 63% specificity, while >2 pretracheal metastatic lymph nodes (AUC: 0.795, p<0.001, J: 0.563) can estimate contralateral paratracheal metastasis with 60% sensitivity and 96.3% specificity. Conclusion: In patients with lateral metastases, the rate of ipsilateral paratracheal metastasis is 85%, while the rate of contralateral paratracheal metastasis is 35.7%. The number of ipsilateral central region or pretracheal lymph node metastases may be helpful in predicting contralateral paratracheal lymph node metastases. Notably, unilateral CND may be performed in the presence of = 2 metastases in the ipsilateral central region. [ABSTRACT FROM AUTHOR]

Objectives: In differentiated thyroid cancer (DTC), radioiodine (RAI) therapy is most frequently employed for remnant ablation or as adjuvant therapy for the remaining disease. The application of RAI to patients classified as intermediate risk (InR) is still a matter of debate. The aim of this study is to analyze the effect of early postoperative risk assessment on RAI use on papillary thyroid cancer patients who are classified as low risk (LoR) or InR. Methods: This is a single-center, prospective registry study. One-hundred-eighty-six patients operated between January 2012 and August 2021 and categorized as LoR or InR were included in this study. All patients had total thyroidectomy and central lymph node dissection by the same endocrine surgeon. An early dynamic risk assessment (EDRA) consisting of neck ultrasonography, serum thyroglobulin (Tg) and anti-Tg levels was performed 6 weeks after surgery. Most of the patients were either followed up without RAI or received ablative low activity (30-50 mCi) RAI based on predetermined criteria. Results: Median follow-up was 63 months. Sixty-six (61%) patients in the LoR group and 43 (56%) patients in the InR group did not receive RAI treatment. Thirty-eight (35%) and 22 (29%) patients in LoR and InR groups received ablative (30-50 mCi) RAI therapy, respectively. In LoR group 5 (4.6%) patients and in InR group 12 (16%) patients received 100 mCi or more RAI activity. Only one patient in the InR group recurred during follow-up. No statistically significant difference regarding local recurrence was found between patients who didn't receive RAI or were treated with RAI within both LoR (p=0.152) and InR (p=0.272) groups. Conclusion: There is consensus for LoR patients about omitting RAI therapy after surgery. Indications for RAI treatment in InR DTC are still under debate. RAI use based on EDRA seems to be a better option than decisions solely made on histopathological risk factors and decreases adjuvant high-activity RAI use without increasing recurrence risk. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the factors associated with bilateral lateral lymph node (LN) metastasis in patients with unilateral papillary thyroid cancer. Methods: The records of the patients who underwent total thyroidectomy with bilateral lateral neck dissection from 2009 to 2020 were investigated. Clinicopathologic characteristics of eligible patients were examined. Results: Of 11 eligible patients, 72.8% had the primary tumor larger than 2 cm (18.2% larger than 4 cm), and central compartment metastasis was present in all patients at the time of the surgery. On the other hand, aggressive subtype, extranodal extension, and lymphovascular and perineural invasion were not identified in most of the patients. Furthermore, preoperative sonography detected all possible contralateral LN metastasis, while computed tomography missed contralateral metastasis in 1 patient. Conclusion: A meticulous evaluation for contralateral LN metastasis using sonography is needed in unilateral papillary thyroid cancer patients with high risk factors. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have recently been identified as crucial biomarkers of papillary thyroid cancer (PTC). In this study, we aimed to investigate the biological function and potential clinical role of lncRNA ENST00000494165 in PTC. From January 2019 to December 2019, 226 PTC patients who underwent preoperative thyroid US-fine needle aspiration biopsy(US-FNAB) and confirmed by postoperative pathology were enrolled at our hospital. Thyroid tissues were collected from FNAB samples and stored in the refrigerator at –80°C. qRT-PCR (quantitative reverse transcriptase-polymerase chain reaction) analysis was performed to detect the relative expression level of ENST00000494165. CCK-8 (Cell Counting Kit-8) and colony formation assay were performed to detect the cell proliferation ability. Cell migration and invasion abilities were evaluated by transwell and scratch assay. We also evaluated the relation between the expression level of ENST00000494165 and the clinicopathological features of PTC. Functional assays demonstrated that the cell proliferation, migration and invasion abilities were all promoted in PTC cell lines when ENST00000494165 expression was overexpressed. The expression of ENST00000494165 in the lymph node metastasis group was significantly higher than that in non-lymph node metastasis group. High level expression of ENST00000494165 was significantly associated with lymph node metastasis of PTC (P < 0.001). The overexpression of ENST00000494165 promoted the progression, migration and invasion abilities of PTC and was significantly correlated with lymph node metastasis in PTC. ENST00000494165 could act as a possible promoter gene and a potential biomarker for PTC. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the most prevalent endocrine cancer worldwide. Approximately 30 % of PTC patients will progress into the advanced or metastatic stage and have a relatively poor prognosis. It is well known that epithelial-mesenchymal transition (EMT) plays a pivotal role in thyroid cancer metastasis, resistance to therapy, and recurrence. Clarifying the molecular mechanisms of EMT in PTC progression will help develop the targeted therapy of PTC. The aberrant expression of some transcription factors (TFs) participated in many pathological processes of cancers including EMT. In this study, by performing bioinformatics analysis, adipocyte enhancer-binding protein 1 (AEBP1) was screened as a pivotal TF that promoted EMT and tumor progression in PTC. In vitro experiments indicated that knockout of AEBP1 can inhibit the growth and invasion of PTC cells and reduce the expression of EMT markers including N-cadherin, TWIST1, and ZEB2. In the xenograft model, knockout of AEBP1 inhibited the growth and lung metastasis of PTC cells. By performing RNA-sequencing, dual-luciferase reporter assay, and chromatin immunoprecipitation assay, Bone morphogenetic protein 4 (BMP4) was identified as a downstream target of AEBP1. Over-expression of BMP4 can rescue the inhibitory effects of AEBP1 knockout on the growth, invasion, and EMT phenotype of PTC cells. In conclusion, these findings demonstrated that AEBP1 plays a critical role in PTC progression by regulating BMP4 expression and the AEBP1-BMP4 axis may present novel therapeutic targets for PTC treatment.

Objective This study aimed to examine the correlation between BRAFV600E status and computed tomography (CT) imaging characteristics in papillary thyroid carcinoma (PTC) and determine if suspicious CT imaging features could predict BRAFV600E status. Methods This retrospective study included patients with pathologically confirmed PTC at the Department of Thyroid Surgery of Zhongshan Hospital, Xiamen University, between July 2020 and June 2022. We compared the clinicopathologic factors and CT findings of nodules with and without the mutation, and the multiple logistical regression test was used to determine independent parameters of the BRAFV600E mutation. Results This study included 381 patients with PTC, among them, BRAFV600E mutation was detected in 314 patients (82.4%). Multivariate logistic regression analysis showed that gender (OR = 0.542, 95% CI [0.296–0.993], P = 0.047) and shape (OR = 0.510, 95% CI [0.275–0.944], P = 0.032) were associated with BRAFV600E mutation. Conclusions Compared to BRAFV600E mutation-negative, BRAFV600E-positive PTC lesions were more likely to be found in female patients and were characterized by irregular shape. However, the CT imaging finding is not enough to predict BRAFV600E status, but an indication.

In the realm of clinical management, Papillary Thyroid Cancer (PTC) stands out as a prevalent thyroid malignancy, characterized by significant metabolic challenges, particularly in the context of carbohydrate metabolism. Recent studies have unveiled promising applications of Dipeptidyl Peptidase-IV (DPP-IV) and Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, which are conventionally employed in the treatment of type 2 diabetes mellitus (T2DM), as potential adjuncts in anticancer therapy. DPP-IV and SGLT2 inhibitors can be imply to counteract the Warburg effect in cancer, with a specific focus on PTC, owing to their potential metabolic advantages and their influence on the tumor microenvironment, achieved by imposing restrictions on glucose accessibility. Consequently, a comprehensive review has been undertaken, involving meticulous examination of the existing body of evidence pertaining to the utilization of DPP-IV and SGLT2 inhibitors in the context of PTC. The mechanisms of action inherent to these inhibitors have been thoroughly explored, drawing upon insights derived from preclinical investigations. Furthermore, this review initiates discussions concerning the implications for future research directions and the formulation of innovative therapeutic strategies for PTC. As the intricate interplay between carbohydrate metabolism, the Warburg effect, and cancer progression garners increasing attention, attaining a comprehensive understanding of the roles played by DPP-IV and SGLT2 inhibitors in PTC management may serve as the cornerstone for novel approaches aimed at enhancing patient care and broadening the spectrum of available therapeutic modalities.

Integrin subunit α3 (ITGA3) is a member of the integrin family and interacts with extracellular matrix proteins. However, there have been few reports regarding the role of ITGA3 in papillary thyroid cancer. The expression levels of ITGA3 were firstly analyzed by bioinformatics tools and in vitro experiments, followed by evaluating its prognostic significance in papillary thyroid cancer patients using Kaplan-Meier, receiver operating characteristic, and Cox regression analyses. Then, cBioportal and GSCA databases were applied to evaluate genetic alterations of ITGA3. Functional enrichment analysis was conducted and the upstream miRNAs of ITGA3 were determined. The results showed that the ITGA3 mRNA and protein levels were higher in the papillary thyroid cancer group than those in the normal group (all P

Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers. However, knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive. In this study, we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer (PTC). In parallel, we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule (BTN) patients. Distinct microbial signatures were identified in PTC, BTN, and their adjacent non-tumor tissues. Intra-thyroid tissue bacteria were verified by means of bacteria staining, fluorescence in situ hybridization, and immunoelectron microscopy. We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN, which included enrichment in PTC of the pathobionts Rhodococcus, Neisseria, Streptococcus, Halomonas, and Devosia, and depletion of the beneficial bacteria Amycolatopsis. These differentially abundant bacteria could differentiate PTC tumor tissues (PTC-T) from BTN tissues (BTN-T) with an area under the curve (AUC) of 81.66%. Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T. Immune-function-corresponding bacteria (i.e., Erwinia, Bacillus, and Acinetobacter) were found to be enriched in PTC with Hashimoto’s thyroiditis. Moreover, our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes, including BRAF, KRAS, IRAK4, CTNNB1, PIK3CA, MAP3K7, and EGFR. In conclusion, our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.

Abstract Introduction Thyroid swellings are prevalent in 4 to 7% of the Indian population and are commonly present in females. Thyroid swelling has been attributed to various causes, such as ingestion of goitrogens and low iodine in the diet in benign, radiation exposure, and genetic in malignancies. Eastern Hyderabad and Nalgonda have a high fluoride content in the ground water, which can potentially disrupt thyroid functioning. Moreover, the region also harbors high uranium content and environmental radiation; hence, a retrospective analysis of the FNAC and histopathology of the thyroid swellings was done to evaluate the paradigm. Method A retrospective analysis of the patient’s records from February 1, 2022, to January 31, 2023, was conducted considering all the patients who presented with thyroid swelling. The variables taken into consideration were age, gender, and FNAC findings. A correlation was also made with the histopathology of the specimen of operated patients. Result A total of 88 medical records of the patients were evaluated, and it was determined that there was a preponderance of females with a ratio of 8.77:1. Majority of the swellings were Benign labeled as Bethesda category 2 (n = 61) followed by category 3 (n = 11). To be considered are the cases of malignancies falling into category 6, which comprise 7.95% (n = 7). The majority of the patients were seen between the ages of 31 to 40 (n = 28), followed by 41 to 50 (n = 25). On comparing with the histopathological reports, two cases of category 5 were found to be having papillary thyroid carcinoma and another with follicular thyroid carcinoma making the number of proven malignancies to be 10.22% (n = 9). Other histopathological findings correlated with the results of FNAC. Conclusion Through this pilot study, we conclude that most thyroid swellings were benign, but there is a higher incidence of thyroid malignancies (10.22%), significantly higher than the country average of 2 to 4%. The higher number of malignant cases can be attributed to many factors, including high fluoride content and environmental radiation. Further studies need to be conducted, taking each element individually.

Background: The aim of the present study is to determine the accuracy of ultrasound imaging in the diagnosis of metastatic lymph nodes compared to postoperative pathology samples of patients with papillary thyroid cancer. Methods: This study was carried out using a descriptive and analytical epidemiological method on 103 known patients with papillary thyroid cancer who referred to Imam and Golestan hospitals in Ahvaz for neck ultrasound from September 2021 to August 2022. A total of 103 patients (including 94 women (91.3%) and 9 men (8.7%)) with papillary thyroid cancer with an average age of (39.8±11.9) were included in the study. The average tumor size in these patients was estimated to be (16.8±10mm). The ultrasound results of these patients before surgery were compared with the pathology results of these patients after surgery. Results: According to the obtained results, metastatic involvement of cervical lymph nodes was diagnosed in 36.6% of patients (38 people). Of these, 30.7% of patients (32 people) were real positive. The results of ultrasound before surgery were shown as false positive in 9.5% of patients (6 people). Lymphatic metastasis was not seen in 58.4% of patients (60 people) before surgery, which was consistent with the pathology result after surgery (true negative). The positive predictive value of examining metastatic lymph nodes by ultrasound was estimated at 84.2% and the negative predictive value at 92.3%. The diagnostic accuracy of ultrasound was 89%, the sensitivity rate was 86%, and the specificity rate was 90% with the area under the curve AUC=0.884 and P

Abstract Background and aim Certain serum levels of microRNAs (miRNAs) throughout the body can be helpful for cancer diagnosis and prognosis. The miRNAs can be secreted from the papillary thyroid cancer (PTC) into the circulatory system. Accordingly, this study aimed to measure the serum levels of miR-146b, miR-155 and miR-375 to evaluate their diagnostic potentials in distinguish of benign from malignant lesions. Materials and methods The serum levels of miRNAs were measured by real-time quantitative RT-PCR among100 patients with benign thyroid nodules and 30 patients with PTC. Results The mean miR-375 and miR-155 expression levels in the PTC group were greater when compared with the benign group. The area under the ROC curve (AUC) was estimated at 0.81 for the miR-375 with 0.76% sensitivity and 0.80% specificity to distinguish between benign and PTC lesions. The AUC was calculated to be 0.75 for the miR-155 with 0.69% sensitivity and 0.90% specificity. Conclusion According to the results of this study, the serum levels of miR-155 and miR-375 were increased in the patients with PTC, which may be useful as alternative seromarkers for the PTC.

Abstract Background The incidental finding of thyroid inclusions in lymph nodes of neck dissections of non-thyroid cancer patients is an unusual event. It is still controversial for pathologists about whether this represents benign inclusions or metastatic papillary thyroid carcinoma (PTC). This study is to analyze clinicopathological features of such cases in an attempt to explore their clinical implications. Methods Pathological data were searched for incidentally detected PTC of cervical lymph nodes in non-thyroid cancer cases. Clinicopathological characteristics were reevaluated and recorded. BRAF V600E protein expression and sequencing analysis was then performed in cases with sufficient tissues. Results 31 patients had an incidental finding of PTC in lymph nodes of patients with non-thyroid cancer. BRAF immunohistochemical staining were performed in 17 metastatic lymph nodes with sufficient tumor tissues, and 6 were positive. BRAF V600E point mutation was detected in 5 of 6 BRAF V600E positive cases. Subsequent imaging examinations of the thyroid showed no nodules or calcifications/benign nodules in 20 patients, and suspected malignant nodules in 5 patients. 12 patients underwent total thyroidectomy or ipsilateral lobectomy, and 6 showed PTC in postoperative pathological examinations. The remaining 19 patients without surgery were kept under active surveillance, and no one had recurrence of PTC. Conclusion Incidentally discovered PTC in lymph nodes has usually interpreted as metastasis from a clinical occult thyroid primary cancer, but primary PTC was not always detected. This suggests it could be double occult lesions. With regards to concurrence with highly malignant tumor, most patients could keep regular surveillance.

The incidence of thyroid cancer, one of the most common forms of endocrine cancer, is increasing rapidly worldwide in developed and developing countries. Various risk factors can increase susceptibility to thyroid cancer, but particular emphasis is put on the role of DNA repair genes, which have a significant impact on genome stability. Polymorphisms of these genes can increase the risk of developing thyroid cancer by affecting their function. In this article, we present a concise review on the most common polymorphisms of selected DNA repair genes that may influence the risk of thyroid cancer. We point out significant differences in the frequency of these polymorphisms between various populations and their potential relationship with susceptibility to the disease. A more complete understanding of these differences may lead to the development of effective prevention strategies and targeted therapies for thyroid cancer. Simultaneously, there is a need for further research on the role of polymorphisms of previously uninvestigated DNA repair genes in the context of thyroid cancer, which may contribute to filling the knowledge gaps on this subject.

Thyroid Cancer (TC) is the most common endocrine malignancy, with increasing incidence globally. Papillary thyroid cancer (PTC), a differentiated form of TC, accounts for approximately 90% of TC and occurs predominantly in women of childbearing age. Although responsive to current treatments, recurrence of PTC by middle age is common and is much more refractive to treatment. Undifferentiated TC, particularly anaplastic thyroid cancer (ATC), is the most aggressive TC subtype, characterized by it being resistant and unresponsive to all therapeutic and surgical interventions. Further, ATC is one of the most aggressive and lethal malignancies across all cancer types. Despite the differences in therapeutic needs in differentiated vs. undifferentiated TC subtypes, there is a critical unmet need for the identification of molecular biomarkers that can aid in early diagnosis, prognosis, and actionable therapeutic targets for intervention. Advances in the field of cancer genomics have enabled for the elucidation of differential gene expression patterns between tumors and healthy tissue. A novel category of molecules, known as non-coding RNAs, can themselves be differentially expressed, and extensively contribute to the up- and downregulation of protein coding genes, serving as master orchestrators of regulated and dysregulated gene expression patterns. These non-coding RNAs have been identified for their roles in driving carcinogenic patterns at various stages of tumor development and have become attractive targets for study. The identification of specific genes that are differentially expressed can give insight into mechanisms that drive carcinogenic patterns, filling the gaps of deciphering molecular and cellular processes that modulate TC subtypes, outside of well-known driver mutations.

Obesity’s role in thyroid cancer development is still debated, as well as its association with aggressive histopathological subtypes (AHSs). To clarify the link between Body Mass Index (BMI) and AHS of differentiated thyroid carcinoma (DTC), we evaluated patients who underwent thyroidectomy for DTC from 2020 to 2022 at four European referral centres for endocrine surgery. Based on BMI, patients were classified as normal-underweight, overweight, or obese. AHSs were defined according to 2022 WHO guidelines. Among 3868 patients included, 34.5% were overweight and 19.6% obese. Histological diagnoses were: 93.6% papillary (PTC), 4.8% follicular (FTC), and 1.6% Hürthle cell (HCC) thyroid carcinoma. Obese and overweight patients with PTC had a higher rate of AHSs (p = 0.03), bilateral, multifocal tumours (p = 0.014, 0.049), and larger nodal metastases (p = 0.017). In a multivariate analysis, BMI was an independent predictor of AHS of PTC, irrespective of gender (p = 0.028). In younger patients ( 1 cm, BMI predicted a higher ATA risk class (p = 0.036). Overweight and obese patients with FTC had larger tumours (p = 0.036). No difference was found in terms of AHS of FTC and HCC based on BMI category. Overweight and obese patients with PTC appear to be at an increased risk for AHS and aggressive clinico-pathological characteristics.

Pancreatic metastasis from papillary thyroid cancer (PTC) is extremely rare; only 18 cases have been reported in the literature. However, several reviews have highlighted similar characteristics between metastatic and primary pancreatic tumors. The patient was a 51-year-old male with a history of total thyroidectomy, modified radical neck dissection, and radioactive iodine ablation for PTC in 2014. Nodules suspected of metastasis were found in both lungs on chest computed tomography (CT). However, after 6 months, a follow-up chest CT showed no increase in size; thus, a follow-up observation was planned. Six years after his initial diagnosis, abdominal CT and pancreas magnetic resonance imaging revealed a 4.7 cm cystic mass with a 2.5 cm enhancing mural nodule in the pancreas tail. We diagnosed the pancreatic lesion as either metastatic cancer or primary pancreas cancer. The patient underwent distal pancreato-splenectomy. After surgery, the pathological report revealed that the mass was metastatic PTC. Pancreatic metastasis from PTC indicates an advanced tumor stage and poor prognosis. However, pancreatectomy can increase the survival rate when the lesion is completely resectable. Therefore, surgical resection should be considered as a treatment for pancreatic metastasis from PTC.

Background and purpose: The occurrence of lymph node metastasis in papillary thyroid cancer (PTC) can have adverse effects on the prognosis of patients. This study aimed to investigate risk factors related to the occurrence of contralateral central lymph node metastases (CLNM) and contralateral lateral lymph node metastases (LLNM) when imaging suspected ipsilateral LLNM in unilateral PTC. Methods: We retrospectively analyzed the clinical data of 526 patients who received surgical treatment in the same treatment group of Jiangsu Cancer Hospital Head and Neck Surgery Department from January 2011 to December 2021. They were initially treated with total thyroidectomy and bilateral central lymph node dissection (CLND) ± lateral lymph node dissection, and their postoperative pathology was uni-PTC. This study analyzed the relevant high-risk factors of contralateral lymph node metastasis. Results: Among the 526 patients, 295 had CLNM, including 272 ipsilateral CLNM, 129 contralateral CLNM and 106 of both sides CLNM; 165 patients had LLNM including 129 ipsilateral LLNM, 18 contralateral LLNM, and 18 of both ipsilateral and contralateral LLNM. Contralateral CLNM occurred in 65 (17.8%) of 365 patients who underwent preventive CLND, and contralateral CLNM was found in 68 (42.2%) of 161 patients with therapeutic CLND. Univariate and multivariate regression analyses showed that contralateral CLNM was associated with maximum diameter of tumor ≥2 cm, multiple foci, no Hashimoto's thyroiditis, tumor invasion, number of CLNM≥6 and age

Pituitary apoplexy is a rare acute condition that can be caused by hemorrhage into the pituitary adenoma or its infarction. This is accompanied by severe headache, nausea, vomiting, photophobia, visual and oculomotor disorders, loss of consciousness, and can also lead to a decrease in the production of a number of hormones by the pituitary gland, i.e. hypopituitarism. We present a clinical case of a 42-year female patient with previously undiagnosed acromegaly and papillary thyroid cancer. The reason for the examination was clinical symptoms of pituitary apoplexy. Right hemithyroidectomy with central and lateral lymphadenectomy was performed for her papillary thyroid cancer, followed by radioactive iodine therapy due to an increased risk of cancer progression. Hemorrhage into the pituitary adenoma in this patient has led to panhypopituitarism and remission of acromegaly. Insulin-like growth factor 1 and growth hormone levels during oral glucose tolerance test were within the reference values, which made the diagnosis of acromegaly challenging.

Abstract Background Leiomyosarcoma (LMS) is a soft tissue malignant tumor that has a predilection to the abdominopelvic and limb smooth muscles. LMS of the thyroid is exceptionally rare. Papillary thyroid cancer (PTC) is the most common thyroid malignancy and originates from the thyroid epithelial layer. To our knowledge, the presence of both tumors in the same patient has not been reported previously. Case presentation & literature review A 42-year-old woman presented with a progressively enlarging neck mass for a few months. She underwent left thyroid lobectomy, and the histology showed high-grade primary LMS of the thyroid. She subsequently underwent a complete thyroidectomy, which identified a classical PTC on her right lobe. Our comprehensive literature review identified 39 published cases of primary LMS of the thyroid. The average tumor size was 5.88 cm and occurred more in women. The most common presentation was neck mass, followed by compressive symptoms. Recurrence and metastasis were uncommon at 15% and 10–25%, respectively. Conclusion Thyroid LMS is a rare malignancy with a worse prognosis than PTC. A thorough workup must be done to rule out metastasis before labeling it as primary thyroid cancer.

Objectives The mitochondrial ribosomal protein L14 (MRPL14) is encoded by a nuclear gene and participates in mitochondrial protein translation. In this study, we aimed to investigate the role of MRPL14 in thyroid cancer. Methods We investigated the association between MRPL14 expression and clinicopathological features using The Cancer Genome Atlas (TCGA) and Chungnam National University Hospital (CNUH) databases. Functional studies of MRPL14, including proliferation, migration, invasion, mitochondrial oxidative phosphorylation and reactive oxygen species (ROS) production, were performed in papillary thyroid cancer (PTC) cell lines (B-CPAP and KTC-1). Results Based on the TCGA dataset, PTC tissues lost mitochondrial integrity and showed dysregulated expression of overall mitoribosomal proteins (MRPs) compared with normal thyroid tissues. Of 78 MRPs, MRPL14 was highly expressed in thyroid cancer tissues. MRPL14 overexpression was significantly associated with advanced tumor stage, extrathyroidal extension, and lymph node metastasis. MRPL14 increased cell proliferation of thyroid cancer and promoted cell migration via epithelial-mesenchymal transition-related proteins. Moreover, MRPL14 knockdown reduced the expression of oxidative phosphorylation complex IV (MTCO1) and increased the accumulation of ROS. Cotreatment with a ROS scavenger restored cell proliferation and migration, which had been reduced by MRPL14 knockdown, implying that ROS functions as a key regulator of the oncogenic effects of MRPL14 in thyroid cancer cells. Conclusion Our findings indicate that MRPL14 may promote cell growth, migration, and invasion by modulating ROS in thyroid cancer cells.

Abstract Background Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy cancer among the malignancies of thyroid. Despite of wide usages of proteomics in PTC, the profile of acetylated proteins in PTC remains unsettled, which is helpful for understanding the carcinogenesis mechanism and identifying useful biomarkers for PTC. Methods The surgically removed specimens of cancer tissues (Ca-T) and adjacent normal tissues (Ca-N) from 10 female patients pathological diagnosed as PTC (TNM stage III) were enrolled in the study. After preparing the pooled extracts of the whole proteins and the acetylated proteins from 10 cases, TMT labeling and LC/MS/MS methods were applied to the assays of global proteomics and acetylated proteomics separately. Bioinformatics analysis, including KEGG, gene ontology (GO) and hierarchical clustering were performed. Some differentially expressed proteins (DEPs) and differentially expressed acetylated proteins (DEAPs) were validated by individual Western blots. Results Controlled with the normal tissues adjacent to the lesions, 147 out of 1923 identified proteins in tumor tissues were considered as DEPs in global proteomics, including 78 up-regulated and 69 down-regulated ones, while 57 out of 311 identified acetylated proteins in tumor tissues were DEAPs in acetylated proteomics, including 32 up-regulated and 25 down-regulated, respectively. The top 3 up- and down-regulated DEPs were fibronectin 1, KRT1B protein and chitinase-3-like protein 1, as well as keratin, type I cytoskeletal 16, A-gamma globin Osilo variant and Huntingtin interacting protein-1. The top 3 up- and down-regulated DEAPs were ribosomal protein L18a-like protein, alpha-1-acid glycoprotein 2 and eukaryotic peptide chain release factor GTP-binding subunit ERF3A, as well as trefoil factor 3, thyroglobulin and histone H2B. Functional GO annotation and KEGG pathway analysis based on the DEPs and DEAPs showed completely different changing pictures. Contrary to the top 10 up- and -down regulated DEPs, most of which were addressed in PTC and other types of carcinomas, changes of the majority DEAPs were not mentioned in the literatures. Conclusions Taken the profiling of the global and acetylated proteomics together will provide more broad view of protein alterations on the carcinogenesis and new direction for selecting biomarker for diagnosis of PTC.

Abstract Background Struma ovarii is an unusual ovarian teratoma containing predominantly thyroid tissue. Less than 10% of cases undergo malignant transformation in the thyroid tissue and are considered malignant struma ovarii (MSO). MSO have been reported with concurrent thyroid lesions, but molecular data is lacking. Case presentation A 42-year-old female developed MSO and synchronous multifocal subcentimeter papillary thyroid carcinoma (PTC). The patient underwent a salpingo-oophrectomy, thyroidectomy, and low-dose radioactive iodine ablation. Both the thyroid subcentimeter PTC and MSO were positive for BRAF V600E mutation, and microRNA expression profiles were similar across all tumor deposits. However, only the malignant component demonstrated extensive loss of heterozygosity (LOH) involving multiple tumor suppressor gene (TSG) chromosomal loci. Conclusions We present the first reported case of MSO with synchronous multifocal subcentimeter PTC in the thyroid containing concordant BRAF V600E mutations and resulting with discordant LOH findings. This data suggests that loss of expression in tumor suppressor gene(s) may be an important contributor to phenotypic expression of malignancy.

Abstract Background Polymorphous adenocarcinoma is the third most common malignant salivary gland tumor. Within polymorphous adenocarcinoma, cribriform adenocarcinoma of salivary glands is a rare subtype and resembles papillary thyroid carcinoma histopathologically. Diagnostically, cribriform adenocarcinoma of salivary glands is challenging for pathologists and surgeons alike as initial presentation and cytologic nuclear features can be easily confused with papillary thyroid carcinoma arising from a thyroglossal duct remnant or lingual thyroid. Case presentation A healthy 64-year-old Caucasian woman presented to a community otolaryngologist with a 4-year history of progressive postnasal drip, globus sensation, and eventual dysphonia. Flexible fiberoptic laryngoscopy showed a large, smooth, vallecular lesion filling the oropharynx. Computed tomography imaging of the neck showed a rounded heterogeneous mass centered within the right aspect of the oropharynx measuring 4.2 × 4.4 × 4.5 cm. Fine needle aspiration biopsy was suspicious for papillary carcinoma due to microscopic findings of malignant cells, nuclear grooves, and a powdery chromatin pattern. In the operating room, the tumor was resected en bloc using a lateral pharyngotomy approach with partial resection of the right lateral hyoid. A limited cervical lymphadenectomy was performed to facilitate the lateral pharyngotomy approach and two out of three lymph nodes demonstrated regional metastatic disease. Nuclear grooves, nuclear membrane notching, and occasional intranuclear pseudoinclusions were identified, which are overlapping histopathological characteristics of papillary thyroid carcinoma and cribriform adenocarcinoma of salivary glands. It was negative for thyroglobulin and thyroid transcription factor-1, which was in keeping with cribriform adenocarcinoma of salivary glands rather than papillary thyroid carcinoma. Conclusion It is difficult to distinguish cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma solely by cytology, and the distinct characteristics of regional lymph node metastasis coupled with nuanced histologic differences should be emphasized in the evaluation of patients presenting with neck lymphadenopathy and an unknown primary or tongue mass. If sufficient fine needle aspiration biopsy material is available, thyroid transcription factor-1, thyroglobulin, or molecular testing may prove useful in differentiating cribriform adenocarcinoma of salivary glands from papillary thyroid carcinoma. A misdiagnosis of papillary thyroid carcinoma may lead to inappropriate treatment including unnecessary thyroidectomy. Therefore, it is critical for both pathologists and surgeons to be aware of this uncommon entity to avoid misdiagnosis and subsequent mismanagement.

Background: The 2015 American Thyroid Association (ATA) Guidelines permit thyroid lobectomy (TL) or total thyroidectomy in the management of low-risk papillary thyroid cancer (PTC). As definitive risk-stratification is only possible post-operatively, some patients may require completion thyroidectomy (CT) after final histopathological analysis. Methods: A retrospective cohort study of patients undergoing surgery for low-risk PTC in a tertiary referral centre was undertaken. Consecutive adult patients treated from January 2013 to March 2021 were divided into two groups (pre- and post-publication of ATA Guidelines on 01/01/2016). Only those eligible for lobectomy under rule 35(B) of the ATA Guidelines were included: Bethesda V/VI cytology, 1–4 cm post-operative size and without pre-operative evidence of extrathyroidal extension or nodal metastases. We examined rates of TL, CT, local recurrence and surgical complications. Results: There were 1488 primary surgical procedures performed for PTC on consecutive adult patients during the study period, of which 461 were eligible for TL. Mean tumour size (P = 0.20) and mean age (P = 0.78) were similar between time periods. The TL rate increased significantly from 4.5 to 18% in the post-publication period (P < 0.001). The proportion of TL patients requiring CT (43 vs 38%) was similar between groups (P = 1.0). There was no significant change in complications (P = 0.55) or local recurrence rates (P = 0.24). Conclusion: The introduction of the 2015 ATA Guidelines resulted in a modest but significant increase in the rate of lobectomy for eligible PTC patients. In the post-publication period, 38% of patients who underwent TL ultimately required CT after complete pathological analysis.

Abstract Multiwalled carbon nanotubes (MWCNTs) are being widely investigated in multiple biomedical applications including, and not limited to, drug delivery, gene therapy, imaging, biosensing, and tissue engineering. Their large surface area and aspect ratio in addition to their unique structural, optical properties, and thermal conductivity also make them potent candidates for novel hyperthermia therapy. Here we introduce thyroid hormone stimulating receptor (TSHR) antibody–conjugate–MWCNT formulation as an enhanced tumor targeting and light-absorbing device for the photoablation of xenografted BCPAP papillary thyroid cancer tumors. To ensure successful photothermal tumor ablation, we determined three key criteria that needed to be addressed: (1) predictive pre-operational modeling; (2) real-time monitoring of the tumor ablation process; and (3) post-operational follow-up to assess the efficacy and ensure complete response with minimal side effects. A COMSOL-based model of spatial temperature distributions of MWCNTs upon selected laser irradiation of the tumor was prepared to accurately predict the internal tumor temperature. This modeling ensured that 4.5W of total laser power delivered over 2 min, would cause an increase of tumor temperature above 45 ℃, and be needed to completely ablate the tumor while minimizing the damage to neighboring tissues. Experimentally, our temperature monitoring results were in line with our predictive modeling, with effective tumor photoablation leading to a significantly reduced post 5-week tumor recurrence using the TSHR-targeted MWCNTs. Ultimately, the results from this study support a utility for photosensitive biologically modified MWCNTs as a cancer therapeutic modality. Further studies will assist with the transition of photothermal therapy from preclinical studies to clinical evaluations.

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.

PurposeNeutrophil-lymphocyte ratio (NLR), markers-lymphocyte-to-monocyte ratio (LMR), and platelet to-lymphocyte ratio (PLR) have potential roles as prognostic biomarkers in various cancers. The study was evaluated to investigate the predictive value of the peripheral inflammatory biomarkers in patients with papillary thyroid carcinoma (PTC) before radioiodine therapy to the response of clinical outcomes.MethodsWe retrospectively analyzed the patients diagnosed with PTC at the Second Hospital of Shandong University between September 2018 and January 2020. Patients were divided into low and high inflammatory biomarker groups based on median values. The area under the receiver operating characteristic curves (ROC) and logistic regression were used to explore the potential risk factors.ResultsA total of 692 patients were enrolled, which included 197 (28.4%) males and 495 (71.6%) females. The median values of NLR, LMR and PLR of these patients were 1.7 (range 0.3–5.7), 7.1 (range 1.1–23.4) and 137.6 (range 27.6–497.5), respectively, and the mean values were 1.95 ± 0.82, 7.4 ± 2.5 and 148.7 ± 54.8, respectively. Compared to the lower PLR group, the higher group was significantly associated with gender, tumor size, N stage and thyroglobulin level (P

AbstractPurpose To analyze the outcomes of radiofrequency ablation (RFA) for isthmus papillary thyroid cancer (PTC) versus PTC originating from the lobes.Methods Patients with solitary low-risk PTC treated with RFA between July 2014 and December 2019 were retrospectively reviewed. This study was approved by our institutional review board. Of the 562 patients, 104 and 458 had PTCs located in the thyroid isthmus and thyroid lobes, respectively. Local tumor progression (LTP), LTP-free survival (LTPFS), changes in tumor volume, and complications were compared between the two groups using propensity-score matching (PSM).Results The isthmic and lobar groups showed no significant differences in LTP (2.9% vs. 3.8%), new PTC (2.9% vs. 2.9%), persistent lesions (0.0% vs. 0.2%), or LTPFS after PSM. Before PSM, the two groups showed significant differences in the volume reduction ratio (VRR) of the ablated tumors at 1, 3, 24, 30, and 48 months after RFA, but no differences between the two groups were observed in tumor volume, VRR, or disappearance rate after PSM (p > .05). One patient in the isthmic group presented with coughing, while another complained of hoarseness. Complications did not differ significantly between the two groups (p > .05).Conclusions The outcomes of RFA for patients with low-risk PTC in the thyroid isthmus and thyroid lobes were similar. Therefore, RFA may serve as an alternative treatment option for patients with low-risk isthmic PTC.