Papillary Thyroid Carcinoma Patients Research Articles

Utilizing Immunoglobulin IgG4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis.

Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished. This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm2 were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery. Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm2 was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT. This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.

Diagnostic value of FNAC combined with BRAFV600E mutation detection in Hashimoto’s thyroiditis complicated with papillary thyroid carcinoma

BackgroundThis study aimed to analyze the effect of preoperative fine needle aspiration cytology (FNAC) combined with BRAFV600E mutation detection as compared to that of fine needle aspiration cytology alone on the diagnostic performance of papillary thyroid carcinoma (PTC) combined with Hashimoto’s thyroiditis (HT).MethodPatients with thyroid nodules in Hashimoto’s thyroiditis, who underwent fine-needle aspiration cytology examination and BRAFV600E mutation detection in the puncture eluate at the outpatient clinic, were selected. Finally, 122 patients received surgical treatment and were included in the study. We used postoperative pathological results as the gold standard. Accordingly, we compared the sensitivity, specificity and accuracy of preoperative FNAC alone and FNAC combined with BRAFV600E mutation detection in for the diagnosis of PTC combined with HT.ResultsFor PTC patients with HT, the sensitivity of FNAC diagnosis was 93.69%, the specificity was 90.90% and the accuracy was 93.44%. However, the sensitivity, specificity and accuracy of FNAC combined with BRAFV600E mutation detection were 97.30%, 90.90% and 96.72%, respectively. Therefore, combined detection can improve the sensitivity and accuracy of diagnosis (p<0.05).ConclusionFNAC combined with eluent BRAFV600E mutation detection can improve the sensitivity and accuracy of diagnosis of PTC in the background of HT.

Synergy of nodal factors in predicting recurrence after treatment of N1b papillary thyroid carcinoma.

Nodal factors are important predictors of prognosis for papillary thyroid carcinoma (PTC), but their synergy effect is not well understood. We aimed to explore their synergy effect in predicting recurrence of clinical N1b PTC. Patients who underwent surgery for cN1b PTC from 2013 to 2017 were enrolled. The association between nodal factors and recurrence was assessed using Cox proportional hazards regression models. Interaction and stratified analyses were conducted according to significant nodal factors. Of 1067 cN1b PTC patients included, all nodal factors (bilateral metastasis, largest dimension>3cm, micro and gross extranodal extension (mENE, gENE), No. of metastatic lymph nodes (MLN), lymph node yield (LNY) and ratio (LNR)) were significantly associated with all site and nodal recurrence in the univariate analysis (all P<0.05). Multivariate analyses revealed largest dimension>3cm, gENE and LNR>0.21 were associated with elevated both all site (HR [95%CI], 2.58 [1.67-4.00], 1.87[1.26-3.01], 1.68[1.11-2.42], all P<0.01) and nodal recurrences (HR[95%CI], 2.63[1.67-4.13], 1.90[1.15-3.12], 1.76[1.17-2.66], all P<0.01). LNR and gENE had interactive effect (all site recurrence: P for interaction = 0.009; nodal recurrence: P for interaction = 0.02). LNR was significantly associated with recurrence in patients without gENE (HR[95% CI], all site recurrence: 2.41[1.50-3.87]; nodal recurrence: 2.51[1.52-4.14], all P< 0.001), while when gENE appeared, LNR was no longer associated with recurrence (HR [95% CI], all site recurrence: 0.81[0.43-1.54], P=0.53; nodal recurrence: 0.85[0.43-1.67], P=0.64). Nodal factors have synergy effect in predicting recurrence in cN1b PTC patients. Increasing lymph nodes harvest may only decrease recurrence in patients without gENE, while not in gENE patients.

Comparative long-term outcomes of airway resection and functional reconstruction for papillary thyroid cancer

IntroductionThe surgical management of patients diagnosed with papillary thyroid carcinoma (PTC) and tracheal invasion has been a subject of ongoing discussion, particularly regarding the approach to tracheal functional reconstruction. The objective of this study was to examine the surgical technique and prognosis of PTC patients with tracheal invasion. Materials and methodsThis study employed both univariate and multivariate Cox proportional hazard models to determine predictive factors that affect the progression-free survival (PFS) of PTC patients with tracheal invasion. Cox regression analysis was conducted by using R software version 4.3.1. ResultsIn our study, we included 247 patients with T4a PTC. Among them, 146 patients (59.1 %) were classified as Shin I, 57 patients (23.1 %) as Shin II-III, and 44 patients (17.8 %) as Shin IV. Patients in the Shin I group underwent shaving of the tumours in the airway. The preferred surgical methods in the Shin II, III and IV groups were window resection (66.7 %), sleeve resection (34.8 %) and partial tracheal resection and skin fistula (61.8 %), respectively. Multivariate analysis demonstrated that neither tracheal surgery nor reconstruction procedures had an impact on PFS in T4a PTC patients with tracheal invasion. The 5-year DSS rate for patients receiving radioiodine (RAI) therapy was 87.3 % (p = 0.033). ConclusionThis study confirmed that tracheal surgery and reconstruction methods had no impact on PFS in T4a PTC patients with tracheal invasion in different Shin groups. Furthermore, RAI therapy has the potential to increase the survival rate of patients with preoperative distant metastasis of T4a PTC.

Transoral robotic thyroidectomy via vestibular approach: a retrospective study of 107 cases in a single center

Objective: To investigate the short-term outcome of transoral robotic thyroidectomy. Methods: This is a retrospective case series study. The clinicopathologic characteristics and postoperative results of 107 patients who underwent transoral robotic thyroidectomies in the Department of Thyroid and Breast Surgery of the 960th Hospital of People's Liberation Army from May 2020 to August 2023 were retrospectively analyzed. There were 12 males and 95 females, with an age of (31.8±9.4) years (range: 11 to 55 years), including 20 benign tumors and 87 thyroid papillary carcinoma. Postoperative follow-up was carried out through returning visit and telephone, mainly to observe the recovery of postoperative complications, cosmetic effects and recurrence results. Results: All transoral robotic thyroidectomy was successfully completed without conversion to open surgery. The tumor size of thyroid papillary carcinoma patients was (5.6±2.7) mm (range: 2 to 15 mm). Furthermore, central cervical lymph node metastasis was found in 45 cases. The number of central cervical lymph nodes retrieved and metastasized (M(IQR)) were 11 (8) (range: 3 to 26) and 1 (3) (range: 0 to 13), respectively. There was no recurrent laryngeal nerve injury and permanent hypoparathyroidism. The transient hypoparathyroidism after surgery was 8 cases. Other complications occurred as follows: postoperative infection (n=1), left submandibular perforation (n=1), skin scald (n=1), and perioral numbness (n=1), oral tear (n=2). The postoperative stay was 6 (2) days (range: 3 to 11 days). No local lymph node recurrence or metastasis occurred after a follow-up of (22.6±10.0) months (range: 1.0 to 37.4 months). All patients were satisfied with the postoperative cosmetic results, the aesthetic effect score was 9.3 (0.2) (range: 8.4 to 9.6) one month after surgery. Conclusion: For highly screened patients with early thyroid cancer, experienced surgeons can perform a transoral robotic thyroidectomy that has excellent cosmetic results.

Differentiated Thyroid Cancer in Children and Adolescents: 12-year Experience in a Single Center.

Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of our study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/recurrence. We conducted a retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at our center. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated. A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, 17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) were submitted to RAI. The mean follow-up time was 5.7 ± 3.1 years. Overall, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs 0.0% (0/6), p=0.031]. An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC.

Identification of SUMOylation-related biomarkers in papillary thyroid carcinoma

BackgroundSmall ubiquitin-like modifier (SUMO) modification is increasingly recognized as critical in tumorigenesis and progression. This study identifies biomarkers linked to SUMOylation in papillary thyroid carcinoma (PTC), aiming to advance therapeutic and prognostic strategies.MethodsEmploying PTC datasets and SUMO related genes (SRGs), we utilized univariate Cox regression for prognosis-related SRGs, conducted differential expression analyses, and integrated findings to pinpoint candidate genes. These genes underwent further validation through survival, gene set enrichment, immune infiltration, and drug sensitivity analyses, including external validation via quantitative RT-qPCR. In our final step, we conducted immunohistochemical staining on tumor samples from PTC patients at our center and integrated this with their clinical data to validate BMP8A’s effectiveness in predicting recurrence in PTC.ResultsThree biomarkers—BMP8A, RGS8, and SERPIND1—emerged as significant. Gene Set Enrichment Analysis (GSEA) showed their involvement in immune-related pathways, with differential immune infiltration patterns and drug response correlations observed, underscoring their potential for targeted therapy. Lastly, we validated the efficacy of BMP8A in predicting the recurrence of PTC in patients using clinical and pathological data from our center.ConclusionThe study identifies BMP8A, RGS8, and SERPIND1 as key biomarkers associated with SUMOylation in PTC. Their linkage to immune response and drug sensitivity highlights their importance as targets for therapeutic intervention and prognosis in PTC research.

Lateral lymph node metastasis in papillary thyroid cancer: Is there a difference between PTC and PTMC?

Papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) are generally characterized as less invasive forms of thyroid cancer with favorable prognosis. However, once lateral cervical lymph node metastasis takes place, the prognosis may be significantly impacted. The purpose of this study was to evaluate whether there is a difference in the pattern of lateral lymph node metastasis between PTC and PTMC. A retrospective analysis was performed for PTC and PTMC patients that underwent central area dissection and unilateral lateral neck lymph node dissection (II-V area) between January 2020 and December 2021. Compared with PTMC group, the PTC group exhibited higher incidence of capsule invasion, extrathyroid invasion and lymphatic vessel invasion. Both the number and rate of central lymph nodes metastasis were elevated in the PTC group. While the number of lateral cervical lymph node metastasis was higher, the metastasis rate did not demonstrate significant difference. No significant differences were identified in the lymph node metastasis patterns between the 2 groups. The determination of the extent of lateral neck lymph node dissection solely based on the tumor size may be unreliable, as PTC and PTMC showed no difference in the number and pattern of lateral neck metastasis. Additional clinical data are warranted to reinforce this conclusion. For patients categorized as unilateral, bilateral, or contralateral cervical lymph node metastasis (including level I, II, III, IV, or V) or retropharyngeal lymph node metastasis who require unilateral lateral neck dissection, the size of the primary tumor may not need to be a central consideration when assessing and deciding the extent of lateral neck dissection.

Correlation Between Serum 1,25(OH)2D3, Serum Phosphorus, and Parathyroid Hormone and Parathyroid Function After Central Lymph Node Dissection in Patients with Papillary Thyroid Carcinoma.

This work was to demonstrate the relationship between serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), serum phosphorus (SP), and parathyroid hormone (PTH) and parathyroid function after central lymph node dissection (CLND) in patients with papillary thyroid carcinoma (PTC). 200 PTC patients after CLND were included, who were rolled into a control group (CG) (n = 89 cases without hypoparathyroidism) and an observation group (OG) (n = 111 cases with complicated hypoparathyroidism). The 1,25(OH)2D3, SP, and PTH levels were detected, and the diagnostic effect of these indicators was assessed. The serum PTH levels of patients in CG after surgery were normal relative to those before surgery, while the serum PTH of patients in OG was relatively lower. 1,25(OH)2D3 concentration of patients in OG was also inferior to CG, while the SP level was superior (P < 0.05). Hypoparathyroidism was positively correlated with serum PTH (r = 0.382) and 1,25(OH)2D3 (r = 0.321) and negatively correlated with SP (r = - 0.211). The area under the curve (AUC) (0.893), sensitivity (90.83%), and specificity (94.77%) of the joint diagnosis of 1,25(OH)2D3 + SP + PTH were greatly superior to those of the single diagnosis and the pairwise diagnosis with the three indicators (P < 0.05). Hypoparathyroidism in patients with PTC after CLND surgery was positively correlated with 1,25(OH)2D3 and PTH and negatively correlated with SP concentration. In addition, the combination diagnosis of 1,25(OH)2D3, PTH, and SP worked well.

Thyroglobulin Antibodies and Tumor Epitope-Specific Cellular Immunity in Papillary Thyroid Cancer.

Papillary thyroid carcinoma (PTC) is characterized by T cell infiltration and frequently by the presence of anti-thyroglobulin antibodies (TgAbs). The role of cellular immunity and of TbAbs in this context is a matter of debate. The aim of our study was to correlate the presence of TgAbs, tumor epitope-specific T cells and the clinical outcome of PTC patients. We studied n=183 consecutive patients with a diagnosis of PTC which were treated with total thyroidectomy plus 131I ablation. During a follow-up of in mean 97 months, most of the PTC patients had no signs of tumor relapse (n=157 patients). In contrast, one patient had serum Tg levels above the detection limit and<1 ng/ml, two patients Tg serum levels≥1 ng/ml and<2 ng/ml and n=23 patients had Tg serum levels≥2 ng/ml. Morphological signs of tumor recurrence were seen in 14 patients; all of these patients had serum Tg levels≥2 ng/ml. Importantly, with the exception of one patient, all TgAb positive PTC patients (n=27) had no signs of tumor recurrence as the serum Tg levels were below the assays functional sensitivities. Tetramer analyses revealed a higher number of tumor epitope-specific CD8+T cells in TgAb positive patients compared to TgAb negative PTC patients. In summary, we show that the occurrence of TgAbs may have an impact on the clinical outcome in PTC patients. This might be due to a tumor epitope-specific cellular immunity in PTC patients.

Mcl-1 mediates intrinsic resistance to RAF inhibitors in mutant BRAF papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most frequent form of thyroid cancer. PTC commonly presents with mutations of the serine/threonine kinase BRAF (BRAFV600E), which drive ERK1/2 pathway activation to support growth and suppress apoptosis. PTC patients often undergo surgical resection; however, since the average age of PTC patients is under 50, adverse effects associated with prolonged maintenance therapy following total thyroidectomy are a concern. The development of mutant-selective BRAF inhibitors (BRAFi), like vemurafenib, has been efficacious in patients with metastatic melanoma, but the response rate is low for mutant BRAF PTC patients. Here, we assay the therapeutic response of BRAFi in a panel of human PTC cell lines and freshly biopsied patient samples. We observed heterogeneous responses to BRAFi, and multi-omic comparisons between susceptible and resistant mutant BRAF PTC revealed overrepresented stress response pathways and the absence of compensatory RTK activation – features that may underpin innate resistance. Importantly, resistant cell lines and patient samples had increased hallmarks of failed apoptosis; a cellular state defined by sublethal caspase activation and DNA damage. Further analysis suggests that the failed apoptotic phenotypes may have features of “minority mitochondrial outer membrane permeabilization (MOMP)” – a stress-related response characterized by fragmented and porous mitochondria known to contribute to cancer aggressiveness. We found that cells presenting with minority MOMP-like phenotypes are dependent on the apoptotic regulator, Mcl-1, as treatment with the Mcl-1 inhibitor, AZD5991, potently induced cell death in resistant cells. Furthermore, PI3K/AKT inhibitors sensitized resistant cells to BRAFi; an effect that was at least in part associated with reduced Mcl-1 levels. Together, these data implicate minority MOMP as a mechanism associated with intrinsic drug resistance and underscore the benefits of targeting Mcl-1 in mutant BRAF PTC.

Cervical lymph node metastasis prediction from papillary thyroid carcinoma US videos: a prospective multicenter study

BackgroundPrediction of lymph node metastasis (LNM) is critical for individualized management of papillary thyroid carcinoma (PTC) patients to avoid unnecessary overtreatment as well as undesired under-treatment. Artificial intelligence (AI) trained by thyroid ultrasound (US) may improve prediction performance.MethodsFrom September 2017 to December 2018, patients with suspicious PTC from the first medical center of the Chinese PLA general hospital were retrospectively enrolled to pre-train the multi-scale, multi-frame, and dual-direction deep learning (MMD-DL) model. From January 2019 to July 2021, PTC patients from four different centers were prospectively enrolled to fine-tune and independently validate MMD-DL. Its diagnostic performance and auxiliary effect on radiologists were analyzed in terms of receiver operating characteristic (ROC) curves, areas under the ROC curve (AUC), accuracy, sensitivity, and specificity.ResultsIn total, 488 PTC patients were enrolled in the pre-training cohort, and 218 PTC patients were included for model fine-tuning (n = 109), internal test (n = 39), and external validation (n = 70). Diagnostic performances of MMD-DL achieved AUCs of 0.85 (95% CI: 0.73, 0.97) and 0.81 (95% CI: 0.73, 0.89) in the test and validation cohorts, respectively, and US radiologists significantly improved their average diagnostic accuracy (57% vs. 60%, P = 0.001) and sensitivity (62% vs. 65%, P < 0.001) by using the AI model for assistance.ConclusionsThe AI model using US videos can provide accurate and reproducible prediction of cervical lymph node metastasis in papillary thyroid carcinoma patients preoperatively, and it can be used as an effective assisting tool to improve diagnostic performance of US radiologists.Trial registrationWe registered on the Chinese Clinical Trial Registry website with the number ChiCTR1900025592.

Genetic alterations and allele frequency of BRAF V600E and TERT mutation in papillary thyroid carcinoma with intermediate-to-high recurrence risk: a retrospective study

The predictive value of allele frequency (AF) of BRAF V600E and TERT mutations in papillary thyroid carcinoma (PTC) remains controversial. We aimed to investigate the AF of BRAF V600E and TERT mutations in intermediate-to-high risk PTC and their association between tumor invasiveness, prognosis, and other mutations. Probe hybridization capture and high-throughput sequencing were used to quantitatively test 40 gene loci in 94 intermediate-to-high recurrence risk PTC patients, combined with clinical characteristics and follow-up for retrospective analysis. BRAF V600E mutation AF was linked to a increased risk of thyroid capsule penetration, recurrence, and concurrent mutations. Concurrent mutations could lead to a worse prognosis and increased invasiveness. TERT promoter mutation frequently accompanied other mutations and resulted in a poorer prognosis. However, there was no clear association between the TERT mutation AF and tumor invasiveness or recurrence. The sensitivity and specificity of predicting recurrence in intermediate-to-high risk PTC with BRAF V600E mutation AF > 28.2% were 60 and 80%. Although genetic alterations in PTC can differ among different ethnicities, the AF of BRAF V600E and TERT mutations may be similar. The AF of BRAF V600E has the potential to be a novel indicator in predicting PTC invasiveness and prognosis.

Nomogram to predict central lymph node metastasis in papillary thyroid carcinoma.

Central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) is common. In our study, we built a nomogram to predict CLNM. We retrospectively analyzed 1,392 PTC patients. This group of patients was divided into a training cohort (including 1,009 patients) and a validation cohort (including 383 patients). Analyses of the correlation between inflammatory indicators, ultrasonic characteristics, pathological characteristics and CLNM were conducted. In the training cohort and validation cohort, the metastatic rates of CLNM were 60.16% and 64.23%, respectively. Univariate and multivariate logistic regression analyses demonstrated that Hashimoto's thyroiditis (HT), calcification, multifocality, capsule invasion, PLR (platelet-lymphocyte ratio) ≤ 130.34, large tumors and middle and lower positions were independent risk factors for CLNM. Then, we constructed a nomogram. The nomogram had good discrimination regardless of whether there was CLNM, with a C-index of 0.809. The calibration curve indicated that the nomogram had good visual and quantitative consistency (p = 0.213). Decision curve analysis showed that the nomogram improved the net clinical benefit with a threshold probability of 0-82% in the training cohort and 0-71% in the validation cohort. We constructed a nomogram to predict CLNM in PTC and assist surgeons in making personalized clinical decisions for PTC.

Deep learning-based computer-aided diagnosis system for the automatic detection and classification of lateral cervical lymph nodes on original ultrasound images of papillary thyroid carcinoma: a prospective diagnostic study.

This study aims to develop a deep learning-based computer-aided diagnosis (CAD) system for the automatic detection and classification of lateral cervical lymph nodes (LNs) on original ultrasound images of papillary thyroid carcinoma (PTC) patients. A retrospective data set of 1801 cervical LN ultrasound images from 1675 patients with PTC and a prospective test set including 185 images from 160 patients were collected. Four different deep leaning models were trained and validated in the retrospective data set. The best model was selected for CAD system development and compared with three sonographers in the retrospective and prospective test sets. The Deformable Detection Transformer (DETR) model showed the highest diagnostic efficacy, with a mean average precision score of 86.3% in the retrospective test set, and was therefore used in constructing the CAD system. The detection performance of the CAD system was superior to the junior sonographer and intermediate sonographer with accuracies of 86.3% and 92.4% in the retrospective and prospective test sets, respectively. The classification performance of the CAD system was better than all sonographers with the areas under the curve (AUCs) of 94.4% and 95.2% in the retrospective and prospective test sets, respectively. This study developed a Deformable DETR model-based CAD system for automatically detecting and classifying lateral cervical LNs on original ultrasound images, which showed excellent diagnostic efficacy and clinical utility. It can be an important tool for assisting sonographers in the diagnosis process.

Feasibility of active surveillance in patients with clinically T1b papillary thyroid carcinoma ≤1.5 cm in preoperative ultrasonography: MASTER study.

Active surveillance (AS) is generally accepted as an alternative to immediate surgery for papillary thyroid carcinoma (PTC) measuring ≤1.0 cm (cT1a) without risk factors. This study investigated the clinicopathologic characteristics of PTCs measuring ≤2.0 cm without cervical lymph node metastasis (cT1N0) by tumor size group to assess the feasibility of AS for PTCs between 1.0 cm and 1.5 cm (cT1b≤1.5). This study enrolled clinically T1N0 patients with preoperative ultrasonography information (n= 935) from a cohort of 1259 patients who underwent lobectomy and were finally diagnosed with PTC from June 2020 to March 2022. The cT1b≤1.5 group (n = 171; 18.3 %) exhibited more lymphatic invasion and occult central lymph node (LN) metastasis with a higher metastatic LN ratio than the cT1a group (n = 719; 76.9 %). However, among patients aged 55 years or older, there were no significant differences in occult central LN metastasis and metastatic LN ratio between the cT1a, cT1b≤1.5, and cT1b>1.5 groups. Multivariate regression analyses revealed that occult central LN metastasis was associated with age, sex, tumor size, extrathyroidal extension, and lymphatic invasion in patients under 55, while in those aged 55 or older, it was associated only with age and lymphatic invasion. For PTC patients aged 55 years or older with cT1b≤1.5, AS could be a viable option due to the absence of a significant relationship between tumor size and occult central LN.

Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

A prediction model based on random survival forest analysis of the overall survival of elderly female papillary thyroid carcinoma patients: a SEER-based study.

Papillary thyroid carcinoma (PTC) is a common malignancy whose incidence is three times greater in females than in males. The prognosis of ageing patients is poor. This research was designed to construct models to predict the overall survival of elderly female patients with PTC. We developed prediction models based on the random survival forest (RSF) algorithm and traditional Cox regression. The data of 4539 patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Twelve variables were analysed to establish the models. The C-index and the Brier score were selected to evaluate the discriminatory ability of the models. Time-dependent receiver operating characteristic (ROC) curves were also drawn to evaluate the accuracy of the models. The clinical benefits of the two models were compared on the basis of the DCA curve. In addition, the Shapley Additive Explanations (SHAP) plot was used to visualize the contribution of the variables in the RSF model. The C-index of the RSF model was 0.811, which was greater than that of the Cox model (0.781). According to the Brier score and the area under the ROC curve (AUC), the RSF model performed better than the Cox model. On the basis of the DCA curve, the RSF model demonstrated fair clinical benefit. The SHAP plot showed that age was the most important variable contributing to the outcome of PTC in elderly female patients. The RSF model we developed performed better than the Cox model and might be valuable for clinical practice.

Patterns of cervical lymph node involvement in mono-focal papillary thyroid carcinoma patients with different capsular status: A multi-center analysis

ObjectiveThe characteristics of cervical lymph node involvement in papillary thyroid carcinoma (PTC) patients with different degree of capsular invasion remains unclear, especially for those with mono-focal lesion who have traditionally been considered as low neck metastasis risk subgroup. Study designRetrospective cohort study. SettingThree academic teaching hospital. MethodsA total of 1276 mono-focal PTC patients were retrospectively analyzed. ResultsMono-focal PTC patients with extrathyroidal extension (ETE) showed significantly higher central lymph node metastasis (CLNM) rate than those without. For patients with no gross ETE (gETE), those with minimal ETE (mETE) also showed more commonly CLNM than those with encapsulated lesions. However, the lateral lymph node metastasis (LLNM) rates of patients with mETE and encapsulated tumors were comparable, both lower than that of patients with gETE. Age ≥40, male, and MTD ≥0.5 cm were identified as independent risk factors of CLNM for those with encapsulated tumors and were enrolled for creating a prediction model. In terms of LLNM, only MTD ≥1.0 cm was confirmed as independent risk factors of LLNM for patients with positive gETE. ConclusionsThe presence and degree of ETE may have different effects on the risk of central and lateral lymph node metastasis. gETE demonstrates a strong correlation with both CLNM and LLNM while mETE is only associated with CLNM in mono-focal PTC patients. A comprehensive model is established in the aim of predicting neck involvement according to the capsular status and the corresponding stratified risk factors, which may aid clinical decision-making for the management of neck regions.

Metabolic Profiles and Blood Biomarkers to Discriminate between Benign Thyroid Nodules and Papillary Carcinoma, Based on UHPLC-QTOF-ESI+-MS Analysis.

In this study, serum metabolic profiling of patients diagnosed with papillary thyroid carcinoma (PTC) and benign thyroid pathologies (BT) aimed to identify specific biomarkers and altered pathways when compared with healthy controls (C). The blood was collected after a histological confirmation from PTC (n = 24) and BT patients (n = 31) in parallel with healthy controls (n = 81). The untargeted metabolomics protocol was applied by UHPLC-QTOF-ESI+-MS analysis and the statistical analysis was performed using the MetaboAnalyst 5.0 platform. The partial least squares-discrimination analysis, including VIP values, random forest graphs, and heatmaps (p < 0.05), was complemented with biomarker analysis (with AUROC ranking) and pathway analysis, suggesting a model for abnormal metabolic pathways in PTC and BT based on 166 identified metabolites. There were 11 classes of putative biomarkers selected that were involved in altered metabolic pathways, e.g., polar molecules (amino acids and glycolysis metabolites, purines and pyrimidines, and selenium complexes) and lipids including free fatty acids, bile acids, acylated carnitines, corticosteroids, prostaglandins, and phospholipids. Specific biomarkers of discrimination were identified in each class of metabolites and upregulated or downregulated comparative to controls, PTC group, and BT group. The lipidomic window was revealed to be more relevant for finding biomarkers related to thyroid carcinoma or benign thyroid nodules, since our study reflected a stronger involvement of lipids and selenium-related molecules in metabolic discrimination.