Shape Sensing of Cantilever Column Using Hybrid Frenet-Serret Homogeneous Transformation Matrix Method.

The Frenet-Serret (FS) framework stands as a pivotal tool in shape sensing for various infrastructures. However, this tool suffers from accumulative errors, particularly at inflection points where the normal vector undergoes sign changes. To minimize the error, the traditional FS framework is modified by incorporating the homogeneous matrix transformation (HMT) method for segments containing inflection points. Additionally, inclination information is also used to calculate the unit tangent vector and the unit norm vector at the start point of each segment. This novel approach, termed the FS-HMT method, aims to enhance accuracy. To validate the effectiveness of the proposed method, a simulation of a cantilever column was conducted using finite element software ANSYS 19.2. The numerical results demonstrate the capability of the proposed method to accurately predict curves with inflection points, yielding a maximum error of 1.1%. Subsequently, experimental verification was performed using a 1 m long spring steel sheet, showcasing an error of 4.9%, which is notably lower than that of the traditional FS framework. Our proposed modified FS framework exhibits improved accuracy, especially in scenarios involving inflection points. These findings underscore its potential as a valuable tool for enhanced shape sensing in practical applications.

SIRT6 drives sensitivity to ferroptosis in anaplastic thyroid cancer through NCOA4-dependent autophagy.

The sirtuin family has been reported to participate in the regulation of oxidative stress, cancer metabolism, aging, and so on. However, few studies have demonstrated its role in ferroptosis. Our previous studies confirmed that SIRT6 is upregulated in thyroid cancer and associated with cancer development by regulating glycolysis and autophagy. In this research, we aimed to elucidate the association between SIRT6 and ferroptosis. RSL3, erastin, ML210, and ML162 were applied to induce ferroptosis. Cell death and lipid peroxidation were measured by flow cytometry. We found that overexpression of SIRT6 significantly increased the sensitivity of cells to ferroptosis, whereas knockout of SIRT6 promoted resistance to ferroptosis. Furthermore, we demonstrated that SIRT6 induced NCOA4-dependent autophagic degradation of ferritin, thus driving sensitivity to ferroptosis. The clinically used ferroptosis inducer sulfasalazine showed promising therapeutic effects on SIRT6-upregulated thyroid cancer cells in vivo. In conclusion, our research demonstrated SIRT6-driven sensitivity to ferroptosis via NCOA4-dependent autophagy and proposed ferroptosis inducers as promising therapeutic agents for anaplastic thyroid cancer patients.

The outcomes and prognostic factors of patients who underwent reoperation for persistent/recurrent papillary thyroid carcinoma.

BACKGROUND: While the most suitable approach for treating persistent/recurrent papillary thyroid carcinoma (PTC) remains controversial, reoperation may be considered an effective method. The efficacy of reoperation in patients with locoregional persistent/recurrent PTC, especially those with unsatisfactory radioactive iodine (RAI) ablation results, is still uncertain. This study aimed to clarify the clinical management strategies for locoregional persistent/recurrent PTC and to explore factors that may affect long-term patient outcomes after reoperation. METHODS: In total, 124 patients who initially underwent thyroidectomy and variable extents of RAI therapy and finally received reoperation for locoregionally persistent/recurrent PTC were included. The parameters associated with recurrence-free survival (RFS) were analysed using a Cox proportional hazards model. RESULTS: Overall, 124 patients presented with structural disease after initial therapy and underwent secondary surgical resection, of whom 32 patients developed further structural disease during follow-up after reoperation. At the time of reoperation, metastatic lymph nodes with extranodal extension (P = 0.023) and high unstimulated thyroglobulin (unstim-Tg) levels after reoperation (post-reop) (P = 0.001) were independent prognostic factors for RFS. Neither RAI avidity nor the frequency and dose of RAI therapies before reoperation affected RFS. CONCLUSIONS: Reoperation is an ideal clinical treatment strategy for structural locoregional persistent/recurrent PTC, and repeated empirical RAI therapies performed prior to reoperation may not contribute to the long-term outcomes of persistent/recurrent PTC patients. Metastatic lymph nodes with extranodal extension and post-reop unstim-Tg > 10.1 ng/mL may predict a poor prognosis.

PRDM16 Inhibits Cell Proliferation and Migration via Epithelial-to-Mesenchymal Transition by Directly Targeting Pyruvate Carboxylase in Papillary Thyroid Cancer.

PRDM16 (known as MEL1), a member of the PR domain zinc finger family, has been implicated in multiple biological processes, including cancers. It is not clear yet whether PRDM16 is involved in tumor progress of papillary thyroid cancer (PTC). We identified the PRDM16 expression level in PTC tissues by qRT-PCR and analyzed its relationship with clinical characteristics in both Fudan University Shanghai Cancer Center (FUSCC) and TCGA cohorts. We tested the function of PRDM16 in PTC cells both in vivo and in vitro. We found a direct downstream target of PRDM16, pyruvate carboxylase (PC), by RNA-sequencing, rescue experiments, luciferase assay, and chromatin immunoprecipitation assay. PRDM16 was downregulated in papillary thyroid cancer tissues and was significantly related with lymph node metastases and extrathyroidal extension in both FUSCC and TCGA cohorts. Overexpression of PRDM16 could attenuate proliferation and migration of PTC cells via inhibiting the epithelial-to-mesenchymal transition process. PC was upregulated in papillary thyroid cancer tissues. Knockdown of PC could inhibit proliferation and migration in TPC-1 and K1 cells. The repression effect on cell proliferation and migration from PRDM16 was PC dependent. PRDM16 could directly bind to the PC promoter and inhibit its expression at the transcription level. Moreover, the mRNA expression level of PRDM16 and PC was negatively related in human PTC tissues. In conclusion, PRDM16 exhibited an antitumor effect and EMT inhibition function in PTC by directly binding with the PC promoter. PRDM16 may be a novel therapeutic target in papillary thyroid cancer.

A 5'-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer.

BACKGROUND: tRNA-derived small noncoding RNAs (sncRNAs) are mainly categorized into tRNA halves (tiRNAs) and fragments (tRFs). Biological functions of tiRNAs in human solid tumor are attracting more and more attention, but researches concerning the mechanisms in tiRNAs-mediated tumorigenesis are rarely. The direct regulatory relationship between tiRNAs and splicing-related proteins remain elusive. METHODS: Papillary thyroid carcinoma (PTC) associated tRNA fragments were screened by tRNA fragments deep sequencing and validated by qRT-PCR and Northern Blot in PTC tissues. The biological function of tRNA fragments were assessed by cell counting kit, transwells and subcutaneous transplantation tumor of nude mice. For mechanistic study, tRNA fragments pull-down, RNA immunoprecipitation, Western Blot, Immunofluorescence, Immunohistochemical staining were performed. RESULTS: Herein, we have identified a 33 nt tiRNA-Gly significantly increases in papillary thyroid cancer (PTC) based on tRFs & tiRNAs sequencing. The ectopic expression of tiRNA-Gly promotes cell proliferation and migration, whereas down-regulation of tiRNA-Gly exhibits reverse effects. Mechanistic investigations reveal tiRNA-Gly directly bind the UHM domain of a splicing-related RNA-binding protein RBM17. The interaction with tiRNA-Gly could translocate RBM17 from cytoplasm into nucleus. In addition, tiRNA-Gly increases RBM17 protein expression via inhibiting its degradation in a ubiquitin/proteasome-dependent way. Moreover, RBM17 level in tiRNA-Gly high-expressing human PTC tissues is upregulated. In vivo mouse model shows that suppression of tiRNA-Gly decreases RBM17 expression. Importantly, tiRNA-Gly can induce exon 16 splicing of MAP4K4 mRNA leading to phosphorylation of downstream signaling pathway, which is RBM17 dependent. CONCLUSIONS: Our study firstly illustrates tiRNA-Gly can directly bind to RBM17 and display oncogenic effect via RBM17-mediated alternative splicing. This fully novel model broadens our understanding of molecular mechanism in which tRNA fragment in tumor cells directly bind RNA binding protein and play a role in alternative splicing.

IL-2 enhanced MHC class I expression in papillary thyroid cancer with Hashimoto's thyroiditis overcomes immune escape in vitro.

The impact of Hashimoto's thyroiditis (HT) on the progression of papillary thyroid cancer (PTC) is still unclear. Interleukin-2 (IL-2) is a growth factor and crucial for HT development. This study aimed at investigating the effect of IL-2 on MHC class I expression in PTC cells and immune activation with experimental treatment for PTC using PTC cell lines. We assessed the expression of IL-2, HLA class I, PD-L1, CD3, CD8 and CD16 molecules in paired PTC tissues and HLA-ABC and PD-L1 expression in IL-2 pre-treated K1, TPC-1 and BCPAP cells by immunohistochemistry, qPCR, flow cytometry and Western blotting. The effect of IL-2 on immunogenicity of PTC cells to stimulate activated human T cells was determined for the percentages of activated CD8+ T cells and their cytokine production as well as PD-1 and PD-L1 expression. Compared with non-tumor tissues, we found that IL-2 expression was up-regulated in PTC tissues, particularly in PTC+HT tissues and correlated positively with HLA-class I, CD3 and CD8 expression in PTC+HT tissues. Conversely, PD-L1 expression decreased in PTC+HT tissues. Treatment with IL-2 significantly up-regulated HLA-class I expression, but down-regulated PD-L1 expression in PTC cells. Co-culture with IL-2-pre-treated PTC cells significantly promoted the proliferation of activated CD8+ T cells and their IL-2 secretion, but decreased their PD-1 expression, accompanied by decreased PD-L1 expression in IL-2-treated PTC cells in vitro. In conclusion, IL-2 up-regulated HLA-class I expression and enhanced anti-tumor T cell immunity during the development of PTC and HT. IL-2 may be a promising immunotherapy for PTC.

LHPP inhibits cell growth and migration and triggers autophagy in papillary thyroid cancer by regulating the AKT/AMPK/mTOR signaling pathway.

In recent decades, the incidence rate of papillary thyroid carcinoma (PTC) has been rapidly increasing. However, the molecular mechanism of the physiological and pathological processes of PTC is still largely unknown. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a tumor suppressor and exerts anti-tumor effect in several human cancers, while the role and underlying mechanism of LHPP in PTC remain vague. In this study, we firstly evaluated the roles of LHPP in PTC and explored its underlying mechanism. Using clinical tissue samples, we detected the level of LHPP in PTC tissues and in matched adjacent normal tissues. Lower level of LHPP was found in PTC tissues than in matched adjacent normal tissues. Similar LHPP expression pattern was found in PTC cell lines when compared with that in normal human thyroid follicular epithelial cells. Then, we over-expressed LHPP in three PTC cell lines and results showed that ectopic LHPP expression consistently reduced cell viability, proliferation, and migration and triggered cell autophagy. Furthermore, over-expression of LHPP inhibited the activation of the AKT/mTOR pathway and promoted the AMPK signaling pathway. In addition, the activation of AKT/mTOR and inhibition of AMPK signaling pathways restored the role of ectopic LHPP expression in PTC cell lines, indicating that LHPP exerts its anti-tumor activity through regulating the AKT/AMPK/mTOR pathway. Ultimately, we illustrated that ectopic LHPP expression inhibited PTC tumor growth in vivo. In conclusion, we revealed that LHPP has an anti-tumor effect in PTC and indicated that LHPP might serve as an effective diagnostic and therapeutic target for PTC.

Tripartite motif containing 14: An oncogene in papillary thyroid carcinoma.

Tripartite motif (TRIM)-containing protein 14 (TRIM14) is implicated in many malignancies. Presently, we studied whether TRIM14 played a role in human papillary thyroid carcinoma (PTC). Herein, TRIM14 was up-regulated in tumor tissues when compared with normal thyroid samples. Among PTC patients, enhanced TRIM14 predicted short recurrence free survival (RFS) time. Then, we found that knockdown of TRIM14 in human PTC K1 cells inhibited cell proliferation, induced cell apoptosis and prevented the tumorigenicity in nude mice. On the contrary, TRIM14 overexpression in human PTC TPC1 cells promoted cell proliferation while inhibited cell apoptosis. TRIM14 exerted its oncogenic activities via promoting the activation of signal transducer and activator of transcription 3 (STAT3). Further, TRIM14 interacted with the suppressor of cytokine-signaling-1 (SOCS1), a negative regulator of STAT3 activation, and knockdown of TRIM14 inhibited SOCS1 ubiquitination. In conclusion, TRIM14 may be a prognostic factor and oncogene in PTC, and may be a potential target for PTC intervention.

Using deep convolutional neural networks for multi-classification of thyroid tumor by histopathology: a large-scale pilot study.

BACKGROUND: To explore whether deep convolutional neural networks (DCNNs) have the potential to improve diagnostic efficiency and increase the level of interobserver agreement in the classification of thyroid nodules in histopathological slides. METHODS: A total of 11,715 fragmented images from 806 patients' original histological images were divided into a training dataset and a test dataset. Inception-ResNet-v2 and VGG-19 were trained using the training dataset and tested using the test dataset to determine the diagnostic efficiencies of different histologic types of thyroid nodules, including normal tissue, adenoma, nodular goiter, papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC). Misdiagnoses were further analyzed. RESULTS: The total 11,715 fragmented images were divided into a training dataset and a test dataset for each pathology type at a ratio of 5:1. Using the test set, VGG-19 yielded a better average diagnostic accuracy than did Inception-ResNet-v2 (97.34% vs. 94.42%, respectively). The VGG-19 model applied to 7 pathology types showed a fragmentation accuracy of 88.33% for normal tissue, 98.57% for ATC, 98.89% for FTC, 100% for MTC, 97.77% for PTC, 100% for nodular goiter and 92.44% for adenoma. It achieved excellent diagnostic efficiencies for all the malignant types. Normal tissue and adenoma were the most challenging histological types to classify. CONCLUSIONS: The DCNN models, especially VGG-19, achieved satisfactory accuracies on the task of differentiating thyroid tumors by histopathology. Analysis of the misdiagnosed cases revealed that normal tissue and adenoma were the most challenging histological types for the DCNN to differentiate, while all the malignant classifications achieved excellent diagnostic efficiencies. The results indicate that DCNN models may have potential for facilitating histopathologic thyroid disease diagnosis.

Multifocal papillary thyroid cancer in children and adolescents: 12-year experience in a single center.

BACKGROUND: Thyroid cancer is the most common endocrine malignant disease in children and adolescents. There is a trend of more conservative strategies including lobectomy and less radioactive iodine therapy (RAI) in multifocal papillary thyroid cancer (PTC) for its good survival outcome. The aim of our study was to define long-time outcome of a large cohort of multifocal PTC patients less than 20 years old treated at our institution. METHODS: Data were collected from 276 cases who were initially diagnosis of PTC under the age of 20 from January 2006 to December 2015 at Fudan University Shanghai Cancer Center. All patients received total/near total thyroidectomy or lobectomy. Therapeutic central-compartment (level VI) and lateral neck lymph node dissection performed for patients with clinically involved neck nodes. RAI therapy used in selected patients. No patients received chemotherapy or kinase inhibitor therapy. Thyroid-stimulating hormone (TSH) suppression therapy was performed in all patients for at least 5 years. RESULTS: Ninety among 276 were multifocal PTC patients and included in this study. The median follow-up time was 54.28 months, ranging from 6.10 to 141.27 months. Fifteen patients had tumor recurrence during the follow-up. On Kaplan-Meier survival curves, lymphovascular invasion and extrathyroidal extension was associated with a decline in recurrence-free survival. However, there was no difference in recurrence-free survival curves in patients no matter which treatment they had received, either lobectomy or total thyroidectomy, RAI or not. CONCLUSIONS: More conservative strategies including lobectomy and less RAI in multifocal PTC among children and adolescents are safe and effective.

Deep convolutional neural network VGG-16 model for differential diagnosing of papillary thyroid carcinomas in cytological images: a pilot study.

Objective: In this study, we exploited a VGG-16 deep convolutional neural network (DCNN) model to differentiate papillary thyroid carcinoma (PTC) from benign thyroid nodules using cytological images. Methods: A pathology-proven dataset was built from 279 cytological images of thyroid nodules. The images were cropped into fragmented images and divided into a training dataset and a test dataset. VGG-16 and Inception-v3 DCNNs were trained and tested to make differential diagnoses. The characteristics of tumor cell nucleus were quantified as contours, perimeter, area and mean of pixel intensity and compared using independent Student's t-tests. Results: In the test group, the accuracy rates of the VGG-16 model and Inception-v3 on fragmented images were 97.66% and 92.75%, respectively, and the accuracy rates of VGG-16 and Inception-v3 in patients were 95% and 87.5%, respectively. The contours, perimeter, area and mean of pixel intensity of PTC in fragmented images were more than the benign nodules, which were 61.01±17.10 vs 47.00±24.08, p=0.000, 134.99±21.42 vs 62.40±29.15, p=0.000, 1770.89±627.22 vs 1157.27±722.23, p=0.013, 165.84±26.33 vs 132.94±28.73, p=0.000), respectively. Conclusion: In summary, after training with a large dataset, the DCNN VGG-16 model showed great potential in facilitating PTC diagnosis from cytological images. The contours, perimeter, area and mean of pixel intensity of PTC in fragmented images were more than the benign nodules.

Deep convolutional neural network Inception-v3 model for differential diagnosing of lymph node in cytological images: a pilot study.

BACKGROUND: In this study, we exploited the Inception-v3 deep convolutional neural network (DCNN) model to differentiate cervical lymphadenopathy using cytological images. METHODS: A dataset of 80 cases was collected through the fine-needle aspiration (FNA) of enlarged cervical lymph nodes, which consisted of 20 cases of reactive lymphoid hyperplasia, 24 cases of non-Hodgkin's lymphoma (NHL), 16 cases of squamous cell carcinoma (SCC), and 20 cases of adenocarcinoma. The images were cropped into fragmented images and divided into a training dataset and a test dataset. Inception-v3 was trained to make differential diagnoses and then tested. The features of misdiagnosed images were further analysed to discover the features that may influence the diagnostic efficiency of such a DCNN. RESULTS: A total of 742 original images were derived from the cases, from which a total of 7,934 fragmented images were cropped. The classification accuracies for the original images of reactive lymphoid hyperplasia, NHL, SCC and adenocarcinoma were 88.46%, 80.77%, 89.29% and 100%, respectively. The total accuracy on the test dataset was 89.62%. Three fragmented images of reactive lymphoid hyperplasia and three fragmented images of SCC were misclassified as NHL. Three fragmented images of NHL were misclassified as reactive lymphoid hyperplasia, one was misclassified as SCC, and one was misclassified as adenocarcinoma. CONCLUSIONS: In summary, after training with a large dataset, the Inception-v3 DCNN model showed great potential in facilitating the diagnosis of cervical lymphadenopathy using cytological images. Analysis of the misdiagnosed cases revealed that NHL was the most challenging cytology type for DCNN to differentiate.

A Novel N Staging System for Predicting Survival in Patients with Medullary Thyroid Cancer.

INTRODUCTION: Despite the crucially prognostic value of lymph node metastasis (LNM) in patients with medullary thyroid cancer (MTC), only the LNM compartment alone was reflected in the 8th edition of the American Joint Committee on Cancer (AJCC) system. OBJECTIVE: This study aimed to incorporate the metastatic lymph node number and metastatic lymph node ratio to generate a more accurate and appropriate N staging system for patients with MTC based on recursive partitioning analysis. DESIGN, SETTING, AND PATIENTS: Two cohorts were included in the analysis, including 1374 MTC patients from the Surveillance, Epidemiology, and End Results database as the derivation cohort, and 164 patients from Fudan University Shanghai Cancer Center as the validation cohort. The predictive performance of the alternative proposed N staging system was compared with that of the 8th AJCC system by using the Harrell concordance index (C-index) and the area under the receiver operating characteristic curve (AUC). RESULTS: In the derivation cohort, the C-index and the AUC at 10 years were 0.778 and 0.789, respectively, for the novel N staging system, and 0.749 and 0.741, respectively, for the 8th AJCC N staging system. Similar trends were also observed in the validation cohort. The proposed N staging system had a better prognostic performance. CONCLUSION: With some improvements, the novel N staging system for MTC suggested from this research may be assessed for potential adoption in the next edition of the AJCC N staging system.

The application of selective neck dissection while preserving the cutaneous branches of cervical plexus in the surgical treatment of differentiated thyroid cancer-experiences from thousands of cases.

Differentiated thyroid cancer (DTC) is associated with the highest propensity for lymph node metastases, given the significant morbidity associated with sacrificing the spinal accessory nerve, surgeons increasingly looked to minimizing functional deficits while maintaining oncologic outcome. We have detailed the technique of a selective neck dissection with more attention to preserving the cervical sensory nerves since 1999 in Fudan University Shanghai Cancer Center. We found that the radical dissection with preservation of the cutaneous branches including the great auricular nerve, the less occipital nerve and the supraclavicular nerve can maximally decrease the complications of paresthesia and dysesthesia postoperatively in the lower neck, the shoulders and the area around the ear in DTC cases when indications were allowed. As long as the principles of cancer surgery are strictly followed, our approach guarantees radical tumor removal and exhibit more functional preservation.

The number and ratio of positive lymph nodes are independent prognostic factors for patients with major salivary gland cancer: Results from the surveillance, epidemiology, and End Results dataset.

INTRODUCTION: To investigate whether the positive lymph node number (PLNN) and positive lymph node ratio (PLNR) could predict the prognosis of patients with major salivary gland cancer (MSGC) and to identify the optimal cutoff points for these variables that stratify patients according to their risk of survival. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify all patients with MSGC between 1988 and 2014. A logistic regression analysis was carried out to evaluate the risk factors for lymph node metastasis (LNM) in MSGC. The X-tile program was used to identify the cutoff values for the PLNN and PLNR in MSGC patients with LNM. Cox proportional hazards regression models were performed to identify the predictors of cancer-specific survival (CSS). RESULTS: In the SEER database, 8668 eligible patients were identified and 3046 of them had LNM. The logistic regression analysis indicated that older age, male sex, larger tumor size, higher grade, tumor extension and high-risk pathology were associated with LNM. The X-tile program showed that a PLNN>4 and a PLNR>0.15 were prognostic indicators of CSS. A multivariable analysis indicated that, after the factors that might potentially affect the prognosis were adjusted for, the PLNN and PLNR were still associated with CSS. CONCLUSIONS: Our Results demonstrated that the PLNN and PLNR were independent prognostic indicators for MSGC patients with lymph node metastasis.

Verteporfin inhibits papillary thyroid cancer cells proliferation and cell cycle through ERK1/2 signaling pathway.

Verteporfin, a FDA approved second-generation photosensitizer, has been demonstrated to have anticancer activity in various tumors, but not including papillary thyroid cancer (PTC). In current pre-clinical pilot study, we investigate the effect of verteporfin on proliferation, apoptosis, cell cycle and tumor growth of PTC. Our results indicate verteporfin attenuates cell proliferation, arrests cell cycle in G2/S phase and induces apoptosis of PTC cells. Moreover, treatment of verteporfin dramatically suppresses tumor growth from PTC cells in xenograft mouse model. We further illustrate that exposure to MEK inhibitor U0126 inactivates phosphorylation of ERK1/2 and MEK in verteporfin-treated PTC cells. These data suggest verteporfin exhibits inhibitory effect on PTC cells proliferation and cell cycle partially via ERK1/2 signalling pathway, which strongly encourages the further application of verteporfin in the treatment against PTC.

Histone methyltransferase KMT5A gene modulates oncogenesis and lipid metabolism of papillary thyroid cancer in vitro.

KMT5A (known as PR-Set7/9, SETD8 and SET8), a member of the SET domain containing methyltransferase family specifically targeting H4K20 for methylation, has been implicated in multiple biological processes. In the present study, we identified that KMT5A was elevated in 50 pairs of papillary thyroid cancer tissue samples and in cell lines K1 and TPC-1 by qRT-PCR and western blotting, as well as by immunohistochemical staining. CCK-8 assay and flow cytometric analysis revealed that inhibition of KMT5A attenuated proliferation and induced apoptosis. Transwell assays revealed that cell migration and invasion were suppressed in KMT5A-knockdown cells. Moreover, the inhibition of KMT5A arrested the cell cycle in the G1/S phase of papillary thyroid cancer cells. The TCGA data revealed that elevated KMT5A expression was significantly correlated with extrathyroidal extension, lymph node metastasis and advanced pathological stage of papillary thyroid cancer. Furthermore, we observed that inhibition of KMT5A suppressed the expression of SREBP1, SCD, FASN and ACC, key molecules involved in lipid metabolism and decreased the level of malondialdehyde in papillary thyroid cancer cells. In conclusion, KMT5A may be a novel oncogenic factor, specifically a regulator for lipid metabolism in papillary thyroid carcinoma.

The Positive Lymph Node Number and Postoperative N-Staging Used to Estimate Survival in Patients with Differentiated Thyroid Cancer: Results from the Surveillance, Epidemiology, and End Results Dataset (1988-2008).

BACKGROUND: Lymph node metastasis is important when evaluating the prognosis of patients with differentiated thyroid cancer (DTC). However, the current N-staging system cannot fully reflect the clinical significance of cervical lymph node metastasis in DTC. In this study, we employed Surveillance, Epidemiology, and End Results (SEER)-registered DTC cases with lymph node metastasis to determine whether the positive lymph node number (PLNN) could be used to improve stratification of patients in terms of survival. METHODS: We used the SEER dataset to identify all DTC patients with at least one positive cervical lymph node who were examined between 1988 and 2008. Multivariable modeling was used to compare cancer-specific survival (CSS) and overall survival (OS) and to calculate different PLNN cutoff points. RESULTS: In total, 14,359 pN + DTC patients identified in the SEER were included. In multivariate Cox regression analysis, the PLNN was significantly associated with both CSS and OS, whereas neither the lymph node ratio (LNR) nor the (numbers of) lymph nodes examined (LNE) were so associated. The highest C-index value (0.933) and the lowest AIC value (9362.687) obtained indicated that the PLNN better predicted the CSS of DTC than did the LNR or LNE. As the p values for both CSS and OS were minimized, and as the PLNN performed best when cases were grouped, PLNN cutoff points of 10 and 3/10 efficiently stratified DTC patients into two and three levels, respectively. Based on the 3/10 trichotomy, the benefits of radioactive iodine (RAI) treatment were evaluated for each group. Such treatment afforded about a 10% survival benefit in patients with more than 10 lymph node metastases. CONCLUSIONS: Compared with the LNR and LNE under different statistical models, PLNN was superior in terms of DTC staging. A cutoff point of 3/10 was optimal for stratifying patients according to prognosis and was of clinical significance in terms of RAI treatment selection.

Cost-effectiveness analysis in papillary thyroid carcinoma patients with different neck dissection strategy: A retrospective cohort study.

BACKGROUND: There are two surgical strategies for bilateral neck dissection (BND), simultaneous and two-stage operations. The aim of the study was to compare the cost-effectiveness BND with this two operations in papillary thyroid carcinoma (PTC) patients. MATERIALS AND METHODS: Consecutive PTC patients undergoing BND were studied retrospectively, and were classified into simultaneous group (Group A) and two-stage group (Group B). Demographic, medical costs, complication and surgical variables were recorded. RESULTS: This study included 256 PTC patients, of which 175 (68.4%) underwent simultaneous BND and 81 (31.6%) patients underwent two-stage. Patients in Group B spent almost twice as much on medical costs as patients in Group A ($4145.3 vs. $7352.5). Group A patients also had shorter hospital stays (11.71 ±â€¯5.12 vs. 23.10 ±â€¯7.11, P < .0001) and surgery times (203.61 ±â€¯61.43min vs. 279.58 ±â€¯71.59min, P < .0001). The average radioactive iodine therapy delay was 67 days in Group B. There was no significant difference in complications (34 vs. 18, P = .605) or disease-free-survival (93.71% vs. 90.12%, P = .243) between the two groups. No difference was found in rates of recurrent laryngeal nerve invasion/resection (12 vs. 11, P = .08; 10 vs. 6, P = .353) or tracheotomy (32 vs. 14, P = .846). However, internal jugular vein invasions were more common in patients with two-stage BND (7 vs. 9, P = .029). CONCLUSION: Simultaneous BND is the most cost-effective strategy for the management of PTC patients without bilateral internal jugular veins invasion, due to lower treatment cost and the ability to avoid RAI delay.

Contrastive study of two screening criteria for active surveillance in patients with low-risk papillary thyroid microcarcinoma: a retrospective analysis of 1001 patients.

Screening out patients who do not require immediate surgery is a growing trend in the field of thyroid research. In this study, we retrospectively compared the application of two surveillance selection criteria in 1001 patients who had undergone surgical treatment of papillary thyroid microcarcinoma (PTMC): low-risk PTMC characteristics defined by Kuma Hospital and CATO consensus on PTMC management of active surveillance. Treatment outcomes were compared between groups. We then analyzed the prognostic indicators of patients who could be managed by surveillance. A total of 724 patients met Kuma screening criteria and 135 met CATO screening criteria. The Kuma low-risk group had a lower incidence of multifocal lesions and CLNM than Kuma high-risk group. We also found more obvious differences in multifocal lesions, CLNM and extrathyroidal extension when evaluating the CATO low-risk criteria in the same manner. On the other hand, patients in the CATO low-risk group had a lower disease progression rate and longer disease-free survival than those in CATO high-risk group. There was no significant difference in prognosis between the Kuma low-risk group and Kuma high-risk group. Our logistic regression analysis showed that a preoperative ultrasound size of >5 mm, male sex, younger age, and malignant lesions without concurrent benign nodules could be predictors of CLNM. In conclusion, patients classified in CATO low-risk criteria had lower proportion of clinicopathological risk factors than the ones in Kuma low-risk criteria. We also found more risk factors may not be suitable for surveillance, such as tumors without concurrent benign nodules.