A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression.

BACKGROUND: The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. METHODS: We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. RESULTS: Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. CONCLUSION: Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

Genetic variations associated with telomere length predict the risk of recurrence of non-oropharyngeal head and neck squamous cell carcinoma.

Genetic factors underlying lymphocyte telomere length (LTL) may provide insights into genomic stability and integrity, with direct links to susceptibility to cancer recurrence. Polymorphisms in telomere-associated genes are strongly associated with LTL and cancer risk, while few large studies have explored the associations between LTL-related polymorphisms and recurrence risk of non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC). Totally 1403 non-OPHNSCC patients were recruited and genotyped for 16 LTL-related polymorphisms identified by genome-wide association studies. Univariate and multivariate analyzes were performed to evaluate associations between the polymorphisms and non-OPHNSCC recurrence risk. Patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes exhibited shorter DFS than those with the rs755017 AA, rs2487999 CC, rs2736108 CC, or s6772228 TT genotypes, respectively (all log-rank p < 0.05). Multivariable analysis confirmed an increased risk of recurrence for patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes (adjusted hazard ratio [aHR]: 1.66, 95% confidence interval [CI]: 1.32-2.07; aHR: 1.77, 95% CI: 1.41-2.23; aHR: 1.56, 95% CI: 1.22-1.99; aHR: 1.52, 95% CI: 1.20-1.93, respectively). Further stratified analysis revealed stronger associations between these genotypes and recurrence risk in ever-smokers and patients undergoing chemoradiotherapy. The similar but particularly pronounced results were observed for the combined risk genotypes of the four significant polymorphisms. This is the first large study on non-OPHNSCC patients showing that LTL-related polymorphisms may modify risk of non-OPHNSCC recurrence individually and jointly, particularly when analyzed in the context of smoking status and personized treatment. Larger studies are needed to validate these results.

Expression of RIPK1 and FADD are associated with chemosensitivity and survival in head and heck squamous cell carcinoma via tanshinone IIA-mediated modulation of the RIPK1-FADD-Caspase 8 complex.

Tanshinone IIA (Tan IIA), a main active ingredient of salvia miltiorrhiza, has a wide range of antitumor effects, while its specific role and mechanism in head and neck squamous cell carcinomas (HNSCC) is not fully understood. Totally 59 primary HNSCC patients underwent two courses of induction chemotherapy before surgery. The association between expression of Fas-Associated Death Domain (FADD) and receptor interacting protein kinase 1 (RIPK1) and chemotherapy resistance and survival were evaluated. The cell counting kit-8 was used to detect the effect of Tan IIA on the activity of cisplatin in chemoresistant HNSCC cells through a series of in vitro experiments. The quantitative real-time reverse-transcription polymerase chain reaction, Western blot analysis and flow cytometry were used. FADD and RIPK1 expressions were differentially expressed in Chemosensitive and drug-resistant patients. Furthermore, patients with tumors exhibiting high expression of FADD and RIPK1 had significantly greater risk for chemoresistance and mortality than patients with tumors that had low levels of these proteins. Moreover, Tan IIA reduced the expression of RIPK1 and FADD in HNSCC chemoresistant cell lines, which could increase the chemosensitivity of cisplatin and promote apoptosis. Overexpression of RIPK1 led to attenuation of therapeutic effects of Tan IIA, which were mainly realized through regulation of the RIPK1-FADD-Caspase 8 complex. This study is the first to demonstrate the clinical value and role of FADD and RIPK1 in the treatment of HNSCC. This work establishes the proapoptotic effects of Tan IIA and its potential to enhance chemosensitivity in HNSCC by modulating the RIPK1-FADD-Caspase 8 complex.

TGF-ß1 and TGF-ßR1 variants are associated with clinical outcomes in smoking-related head and neck cancer patients treated with chemoradiation through modulating microRNA-mediated regulation.

TGF-ß1 and TGF-ßR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-ß1 rs1800470 and TGF-ßR1 rs334348 have emerged as potentially prognostic biomarkers for HPV-related head and neck cancer, while their prognostic effect on survival of smoking-related head and neck cancer remains unknown. This study included 1403 patients with smoking-related head and neck cancer, and all these patients were genotyped for TGF-ß1 rs1800470 and TGF-ßR1 rs334348. Both univariate and multivariate analyses were performed to evaluate associations between the two functional genetic variants in microRNA binding sites of TGF-ß1 and TGF-ßR1 and survivals. Patients with TGF-ß1 rs1800470 CT or CC genotype had 30-35% risk reductions for OS, DSS, and DFS compared to patients with TT genotype among overall patients, ever smokers, and patients administered chemoradiation. Furthermore, patients with TGF-ßR1 rs334348 GA or GG genotype had significant 50-60% risk reductions for OS, DSS, and DFS compared to patients with AA genotype among overall patients and patients administered chemoradiation; among ever smokers, the risk reductions even reached 60-70%. The TCGA dataset was used for validation. These findings suggest that TGF-ß1 rs1800470 and TGF-ßR1 rs334348 significantly affect survival outcomes in patients with smoking-related head and neck cancer, especially in the subgroups of ever smokers and patients treated with chemoradiation. These genetic variants may serve as prognostic indicators for patients with smoking-related head and neck cancer and could play a role in advancing the field of personalized chemoradiation, thereby improving patient survival and quality of life.

Long non-coding RNA ACTA2-AS1 suppresses metastasis of papillary thyroid cancer via regulation of miR-4428/KLF9 axis.

BACKGROUND: Metastasis is the primary cause of recurrence and death in patients with papillary thyroid carcinoma (PTC). LncRNA ACTA2-AS1, a long non-coding RNA, acts as a tumor suppressor in multiple types of human malignancies, while the role of ACTA2-AS1 in PTC metastasis remains unclear. METHODS: The ACTA2-AS1 expression in PTC tissues was analyzed. The sponged roles of ACTA2-AS1 via miR-4428/KLF9 axis were identified using starBase tool. The function of ACTA2-AS1 in PTC was performed with in vitro and in vivo experiments. The correlation between DNA methylation and mRNA expressions of these gene in the TCGA dataset was explored. RESULTS: ACTA2-AS1 expression was downregulated in PTC tissues without metastasis and further decreased in PTC tissues with lymph node metastasis compared with that in normal tissues. Functionally, the overexpression of ACTA2-AS1 inhibited the growth, proliferation, and invasion of PTC cells, whereas its depletion exerted opposite effect. In vivo, ACTA2-AS1 expression inhibited PTC metastasis. Furthermore, ACTA2-AS1 acted as a competing endogenous RNA for miR-4428, thereby positively regulating the expression of miR-4428 target gene, KLF9. Finally, miR-4428 overexpression enhanced invasive potential of PTC cells and significantly weakened the effects of ACTA2-AS1 on promotion and inhibition of KLF9 expression as well as invasive ability of PTC cells, respectively. In the TCGA dataset, the methylation level of ACTA2-AS1 was significantly correlated with its mRNA expression (r = 0.21, p = 2.1 × e-6). CONCLUSIONS: Our findings demonstrate that ACTA2-AS1 functions as a tumor suppressor in PTC progression at least partly by regulating the miR-4428-dependent expression of KLF9.

Gasless Single-Incision Endoscopic Surgery via Subclavicular Approach for Lateral Neck Dissection in Patients with Papillary Thyroid Cancer.

BACKGROUND: The technical difficulties and trauma of remote access methods in endoscopic surgery (ES) for lateral neck dissection (LND) can be daunting for most patients with papillary thyroid cancer (PTC) and surgeons. The purpose of study was to introduce gasless single-incision ES via a subclavicular approach (ESSA) and to explore its safety and efficacy for LND. METHODS: Between January 2022 and February 2023, we retrospectively reviewed 17 patients with PTC who underwent ESSA for LND. In addition, 22 patients who received video-assisted ES (VAES) and 48 patients who underwent open surgery (OP) for LND during the same period were included. Clinicopathological characteristics, complications, and efficacy of the lymph node yield (LNY) were compared between the ESSA and the other two groups (VAES and OP). RESULTS: The LNY from central and lateral neck dissection by ESSA was comparable to that by VAES (9.2 ± 8.1 vs. 9.5 ± 4.2, P = 0.986, and 33.5 ± 11.6 vs. 30.6 ± 9.2, P = 0.382, respectively) and OP (9.2 ± 8.1 vs. 11.0 ± 5.4, P = 0.420, and 33.5 ± 11.6 vs. 31.5 ± 7.9, P = 0.383, respectively). Swallowing impairment scores at 1 and 3 months were significantly lower after ESSA than those after VAES (1.8 ± 1.0 vs. 3.0 ± 1.2, P = 0.003, and 0.9 ± 0.8 vs. 1.7 ± 0.8, P = 0.006, respectively). The cosmetic satisfaction rate 1 month after surgery was significantly higher in the ESSA group than that in the VAES group (100 vs. 31.8%, P < 0.001). CONCLUSIONS: ESSA is a safe and minimally invasive procedure that provides a scarless cervical appearance and has good efficacy for LND. Therefore, ESSA may be a feasible choice for selected patients with N1b PTC with cervical cosmetic needs.

Targeting hnRNPC suppresses thyroid follicular epithelial cell apoptosis and necroptosis through m6A-modified ATF4 in autoimmune thyroid disease.

Both environmental and genetic factors contribute to the etiology of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT). However, the exact pathogenesis and interactions that occur between environmental factors and genes remain unclear, and therapeutic targets require further investigation due to limited therapeutic options. To solve such problems, this study utilized single-cell transcriptome, whole transcriptome, full-length transcriptome (Oxford nanopore technology), and metabolome sequencing to examine thyroid lesion tissues from 2 HT patients and 2 GD patients as well as healthy thyroid tissue from 1 control subject. HT patients had increased ATF4-positive thyroid follicular epithelial (ThyFoEp) cells, which significantly increased endoplasmic reticulum stress. The enhanced sustained stress resulted in cell death mainly including apoptosis and necroptosis. The ATF4-based global gene regulatory network and experimental validation revealed that N6-methyladenosine (m6A) reader hnRNPC promoted the transcriptional activity, synthesis, and translation of ATF4 through mediating m6A modification of ATF4. Increased ATF4 expression initiated endoplasmic reticulum stress signaling, which when sustained, caused apoptosis and necroptosis in ThyFoEp cells, and mediated HT development. Targeting hnRNPC and ATF4 notably decreased ThyFoEp cell death, thus ameliorating disease progression. Collectively, this study reveals the mechanisms by which microenvironmental cells in HT and GD patients trigger and amplify the thyroid autoimmune cascade response. Furthermore, we identify new therapeutic targets for the treatment of autoimmune thyroid disease, hoping to provide a potential way for targeted therapy.

Performance of CT-based deep learning in diagnostic assessment of suspicious lateral lymph nodes in papillary thyroid cancer: a prospective diagnostic study.

BACKGROUND: Preoperative evaluation of the metastasis status of lateral lymph nodes (LNs) in papillary thyroid cancer is challenging. Strategies for using deep learning to diagnosis of lateral LN metastasis require additional development and testing. This study aimed to build a deep learning-based model to distinguish benign lateral LNs from metastatic lateral LNs in papillary thyroid cancer and test the model's diagnostic performance in a real-world clinical setting. METHODS: This was a prospective diagnostic study. An ensemble model integrating a three-dimensional residual network algorithm with clinical risk factors available before surgery was developed based on computed tomography images of lateral LNs in an internal dataset and validated in two external datasets. The diagnostic performance of the ensemble model was tested and compared with the results of fine-needle aspiration (FNA) (used as the standard reference method) and the diagnoses made by two senior radiologists in 113 suspicious lateral LNs in patients enrolled prospectively. RESULTS: The area under the receiver operating characteristic curve of the ensemble model for diagnosing suspicious lateral LNs was 0.829 (95% CI: 0.732-0.927). The sensitivity and specificity of the ensemble model were 0.839 (95% CI: 0.762-0.916) and 0.769 (95% CI: 0.607-0.931), respectively. The diagnostic accuracy of the ensemble model was 82.3%. With FNA results as the criterion standard, the ensemble model had excellent diagnostic performance ( P =0.115), similar to that of the two senior radiologists ( P =1.000 and P =0.392, respectively). CONCLUSION: A three-dimensional residual network-based ensemble model was successfully developed for the diagnostic assessment of suspicious lateral LNs and achieved diagnostic performance similar to that of FNA and senior radiologists. The model appears promising for clinical application.

CT Radiomics-Based Nomogram for Predicting the Lateral Neck Lymph Node Metastasis in Papillary Thyroid Carcinoma: A Prospective Multicenter Study.

RATIONALE AND OBJECTIVES: This study is based on multicenter cohorts and aims to utilize computed tomography (CT) images to construct a radiomics nomogram for predicting the lateral neck lymph node (LNLN) metastasis in the papillary thyroid carcinoma (PTC) and further explore the biological basis under its prediction. MATERIALS AND METHODS: In the multicenter study, 1213 lymph nodes from 409 patients with PTC who underwent CT examinations and received open surgery and lateral neck dissection were included. A prospective test cohort was used in validating the model. Radiomics features were extracted from the CT images of each patient's LNLNs. Selectkbest, maximum relevance and minimum redundancy and the least absolute shrinkage and selection operator (LASSO) algorithm were used in reducing the dimensionality of radiomics features in the training cohort. Then, a radiomics signature (Rad-score) was calculated as the sum of each feature multiplied by the nonzero coefficient from LASSO. A nomogram was generated using the clinical risk factors of the patients and Rad-score. The nomograms' performance was analyzed in terms of accuracy, sensitivity, specificity, confusion matrix, receiver operating characteristic curves, and areas under the receiver operating characteristic curve (AUCs). The clinical usefulness of the nomogram was evaluated by decision curve analysis. Moreover, three radiologists with different working experiences and nomogram were compared to one another. Whole transcriptomics sequencing was performed in 14 tumor samples; the correlation of biological functions and high and low LNLN samples predicted by the nomogram was further investigated. RESULTS: A total of 29 radiomics features were used in constructing the Rad-score. Rad-score and clinical risk factors (age, tumor diameter, location and number of suspected tumors) compose the nomogram. The nomogram exhibited good discrimination performance of the nomogram for predicting LNLN metastasis in the training cohort (AUC, 0.866), internal test cohort (0.845), external test cohort (0.725), and prospective test cohort (0.808) and showed diagnostic capability comparable to senior radiologists, significantly outperforming junior radiologists (p < 0.05). Functional enrichment analysis suggested that the nomogram can reflect the ribosome-related structures of cytoplasmic translation in patients with PTC. CONCLUSION: Our radiomics nomogram provides a noninvasive method that incorporates radiomics features and clinical risk factors for predicting LNLN metastasis in patients with PTC.

Artificial intelligence-based prediction of cervical lymph node metastasis in papillary thyroid cancer with CT.

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.

The ambulatory transoral endoscopic thyroidectomy vestibular approach is safe and economical for patients with thyroid nodules.

Background: Ambulatory thyroid surgery has been increasingly performed in recent years. However, the feasibility of the ambulatory transoral endoscopic thyroidectomy vestibular approach (TOETVA) has not been evaluated. We aimed to evaluate the safety, economy, and mental health outcomes of ambulatory TOETVA. Methods: We retrospectively reviewed the data of patients who underwent TOETVA between March 2019 and August 2022. The procedure was performed by a skilled surgical team from the Department of Thyroid Surgery of the affiliated Yantai Yuhuangding Hospital of Qingdao University. Patients were enrolled in the ambulatory (n=166) and conventional (n=290) groups, based on their chosen procedure. We analyzed patients' clinical characteristics, surgical outcomes, Hamilton Anxiety Rating Scale (HAM-A) scores, and hospitalization costs. Results: Of 456 patients, 166 underwent ambulatory TOETVA and 290 underwent conventional TOETVA. No significant differences were found in clinical and surgical characteristics between the groups, including sex (P=0.363), age (P=0.077), body mass index (P=0.351), presence of internal diseases (P=0.613), presence of Hashimoto's thyroiditis (P=0.429), pathology (P=0.362), maximum tumor diameter (P=0.520), scope of surgery (P=0.850), or operative time (P=0.351). There were no significant differences in maximum tumor diameter (P=0.349), extrathyroidal tissue invasion (P=0.516), number of retrieved central lymph nodes (P=0.069), or metastatic central lymph nodes (P=0.897) between the groups. No significant differences were found in complications, including transient hypoparathyroidism (P=0.438), transient vocal cord palsy (P=0.876), transient mental nerve injury (P=0.749), permanent mental nerve injury (P=0.926), and other complications (P=1.000). Ambulatory patients had shorter hospital stays (P<0.001) and reduced hospitalization costs (P<0.001). There was no significant difference in HAM-A scores between the groups (P=0.056). Conclusions: Ambulatory TOETVA is a safe, feasible, and cost-effective procedure for selected patients. This procedure resulted in shorter hospital stays, decreased medical costs, and did not increase patient anxiety. To ensure patient safety, surgical teams must inform patients of the indications, when to seek help, and how to receive the fastest medical attention.

Extrathyroidal Extension Prediction of Papillary Thyroid Cancer With Computed Tomography Based Radiomics Nomogram: A Multicenter Study.

Objectives: To develop and validate a Computed Tomography (CT) based radiomics nomogram for preoperative predicting of extrathyroidal extension (ETE) in papillary thyroid cancer (PTC) patients. Methods: A total of 153 patients were randomly assigned to training and internal test sets (7:3). 46 patients were recruited to serve as an external test set. A radiologist with 8 years of experience segmented the images. Radiomics features were extracted from each image and Delta-radiomics features were calculated. Features were selected by using one way analysis of variance and the least absolute shrinkage and selection operator in the training set. K-nearest neighbor, logistic regression, decision tree, linear-support vector machine (linear -SVM), gaussian-SVM, and polynomial-SVM were used to build 6 radiomics models. Next, a radiomics signature score (Rad-score) was constructed by using the linear combination of selected features weighted by their corresponding coefficients. Finally, a nomogram was constructed combining the clinical risk factors with Rad-scores. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curve were performed on the three sets to evaluate the nomogram's performance. Results: 4 radiomics features were selected. The six models showed the certain value of radiomics, with area under the curves (AUCs) from 0.642 to 0.701. The nomogram combining the Rad-score and clinical risk factors (radiologists' interpretation) showed good performance (internal test set: AUC 0.750; external test set: AUC 0.797). Calibration curve and DCA demonstrated good performance of the nomogram. Conclusion: Our radiomics nomogram incorporating the radiomics and radiologists' interpretation has utility in the identification of ETE in PTC patients.

Comparison Between Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) and Conventional Open Thyroidectomy for Patients Undergoing Total Thyroidectomy and Central Neck Dissection: A Propensity Score-Matching Analysis.

Background: Use of the novel transoral endoscopic thyroidectomy vestibular approach (TOETVA) is increasing worldwide. Although several studies have compared safety and efficacy of TOETVA and other approaches, most focused on comparisons in the context of unilateral thyroidectomy. Therefore, the present study aimed to compare the safety and surgical completeness of TOETVA with conventional open thyroidectomy (COT) in patients with papillary thyroid carcinoma (PTC) undergoing total thyroidectomy and central neck dissection. Methods: The medical records of patients who underwent TOETVA or COT by a single surgeon between June 2017 and October 2021 were retrospectively reviewed. All patients were diagnosed with PTC and underwent total thyroidectomy with central neck dissection. Propensity score-matching (PSM) was used to reduce potential selection bias and to adjust for differences in baseline clinicopathological characteristics. Results: After PSM, 84 (TOETVA: 28; COT: 56) patients remained in the study population. There were no significant differences in sex, mean age, combined thyroiditis, tumor size, capsule invasion, tumor multifocality in the same lobe, or tumor location between the groups. Operative time was longer (190.54 ± 28.26 vs. 123.93 ± 29.78 min, P<0.001), while postoperative drainage volume (161.07 ± 225.30 vs. 71.16 ± 28.56 ml, P=0.045) was greater, in the TOETVA group than in the COT group. The groups exhibited no significant differences in the mean number of central lymph nodes retrieved (9.39 ± 4.01 vs. 10.71 ± 5.17, P=0.202), mean number of metastatic central lymph nodes (1.36 ± 1.93 vs. 1.77 ± 2.31, P=0.421), postoperative mean thyroglobulin levels (0.08 ± 0.24 vs. 0.10 ± 0.27, P=0.686), rate of transient hypoparathyroidism (TOETVA: 67.9% vs. COT: 66.1%, P=0.870), rate of transient vocal cord palsy (TOETVA: 0% vs. COT: 1.8%, P=1.000), or other complications (TOETVA: 3.6% vs. COT: 0%, P=0.333). Conclusions: TOETVA is a safe approach in select patients with PTC and exhibits similar efficacy to COT in terms of surgical completeness.

Transoral versus gasless transaxillary endoscopic thyroidectomy: a comparative study.

This study aimed to compare the surgical safety and outcomes of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) and gasless endoscopic thyroidectomy transaxillary approach (GETTA). This retrospective study assessed 150 patients managed with the TOETVA at the Yantai Yuhuangding hospital and 150 patients managed via the GETTA at the Zhenjiang Provincial People's Hospital. The procedures were compared in terms of workspace creation time, operating time, complications, post-operative complaints, cosmetic satisfaction, and the efficacy of central neck lymph-node dissection. There was no significant between-group difference in terms of post-operative complications. The average workspace creation and operating times were significantly shorter for GETTA than for TOETVA (P values for both < 0.001). The average number of lymph nodes dissected from the central compartment of the neck was higher in the TOETVA group than in the GETTA group (7.2 ± 4.6 vs. 3.9 ± 3.0, P < 0.001). The mean swallowing impairment index-6 scores at 1 month were significantly lower in the GETTA group than in the TOETVA group (1.5 ± 1.2 vs 2.6 ± 1.4, P < 0.001). Over 97% of all patients (both groups) were either satisfied or very satisfied with the cervical cosmetic outcomes at 3 months post-surgery (P = 0.099). TOETVA and GETTA are both safe procedures with good cervical cosmetic outcomes for well-selected patients. Although TOETVA is more efficacious in terms of central lymph nodes dissection, GETTA has a greater time-cost advantage.

Computed Tomography-Based Radiomics Model to Predict Central Cervical Lymph Node Metastases in Papillary Thyroid Carcinoma: A Multicenter Study.

Objectives: This study aimed to develop a computed tomography (CT)-based radiomics model to predict central lymph node metastases (CLNM) preoperatively in patients with papillary thyroid carcinoma (PTC). Methods: In this retrospective study, 678 patients with PTC were enrolled from Yantai Yuhuangding Hot3spital (n=605) and the Affiliated Hospital of Binzhou Medical University (n=73) within August 2010 to December 2020. The patients were randomly divided into a training set (n=423), an internal test set (n=182), and an external test set (n=73). Radiomics features of each patient were extracted from preoperative plain scan and contrast-enhanced CT images (arterial and venous phases). One-way analysis of variance (ANOVA) and least absolute shrinkage and selection operator algorithm were used for feature selection. The K-nearest neighbor, logistics regression, decision tree, linear-support vector machine (linear-SVM), Gaussian-SVM, and polynomial-SVM algorithms were used to establish radiomics models for CLNM prediction. The clinical risk factors were selected by ANOVA and multivariate logistic regression. Incorporated with clinical risk factors, a combined radiomics model was established for the preoperative prediction of CLNM in patients with PTCs. The performance of the combined radiomics model was evaluated using the receiver operating characteristic (ROC) and calibration curves in the training and test sets. The clinical usefulness was evaluated through decision curve analysis (DCA). Results: A total of 4227 radiomic features were extracted from the CT images of each patient, and 14 non-zero coefficient features associated with CLNM were selected. Four clinical variables (sex, age, tumor diameter, and CT-reported lymph node status) were significantly associated with CLNM. Linear-SVM led to the best prediction model, which incorporated radiomic features and clinical risk factors. Areas under the ROC curves of 0.747 (95% confidence interval [CI] 0.706-0.782), 0.710 (95% CI 0.634-0.786), and 0.764 (95% CI 0.654-0.875) were obtained in the training, internal, and external test sets, respectively. The linear-SVM algorithm also showed better sensitivity (0.702 [95% CI 0.600-0.790] vs. 0.477 [95% CI 0.409-0.545]) and accuracy (0.670 [95% CI 0.600-0.738] vs. 0.642 [95% CI 0.569-0.712]) than an experienced radiologist in the internal test set in the combined radiomics model. The calibration plot reflected a favorable agreement between the actual and estimated probabilities of CLNM. The DCA indicated the clinical usefulness of the combined radiomics model. Conclusion: The combined radiomics model is a non-invasive preoperative tool that incorporates radiomic features and clinical risk factors to predict CLNM in patients with PTC.

Clinical Relevance and Management of Recurrent Laryngeal Nerve Inlet Zone Lymph Nodes Metastasis in Papillary Thyroid Cancer.

Background: Recurrent nodal disease often occurs in recurrent laryngeal nerve inlet zone (RLNIZ), leading to difficult surgical management. Methods: Medical records of 947 patients with PTC and 33 patients with recurrent PTC were retrospectively reviewed. Totally 169 sides of RLNIZ dissection in 152 patients (17 cases were bilateral and 135 cases were unilateral) with primary surgery and 4 patients with structural recurrent disease were included for the analysis. Results: The rate of lymph node metastasis in RLNIZ was 31.3% (47/150). The incidence of transient hypoparathyroidism was 5.9% and no RLN injury and permanent hypoparathyroidism occurred. RLNIZ lymph nodes metastasis (LNM) was significantly associated with age <45 years, larger tumor size, number of CNLNM, and lateral node metastasis. CNLNM and lateral node metastasis were independent risk factors for RLNIZ LNM. Recurrent nodal disease in RLNIZ was identified in four of 33 patients and permanent recurrent laryngeal nerve (RLN) injury was observed in one of four patients. Conclusion: Lymph nodes in RLNIZ are usually involved in patients with heavy tumor burden and can be removed safely at initial surgery. Once central or lateral LNM was confirmed preoperatively or intraoperatively, RLNIZ lymph node dissection should be carefully performed to reduce the rate of structural recurrence in the central compartment.

The sensorimotor changes of the lower lip and chin after transoral endoscopic thyroidectomy vestibular approach.

The transoral endoscopic thyroidectomy vestibular approach (TOETVA) can lead to abnormal sensorimotor changes in the lower lip and chin because of its incision design. This study aimed to explore the surgical outcomes of these changes after TOETVA. A total of 122 patients who underwent TOETVA were reviewed. The original incision design was used for the 39 patients in group A and a modified incision design was used for the 83 patients in group B. The sensorimotor changes in the lower lip and chin were compared. Varying degrees of paresthesia of the lower lip and chin (PoLC) were noted in all group A patients. Approximately 20.5% of group B patients did not suffer from PoLC, and the degree of PoLC in group B was significantly lower (P < 0.001). Abnormal motor function of the lower lip was noted for 23.1% of the patients in group A and 2.4% of those in group B. The incision design plays an important role in the morbidity of sensorimotor changes in the lower lip and chin. Our modified incision design seems minimally invasive and feasible for patients who undergo TOETVA.

Safety and surgical outcomes of transoral endoscopic thyroidectomy vestibular approach for papillary thyroid cancer: A two-centre study.

OBJECTIVE: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been increasingly used to treat patients with papillary thyroid cancer (PTC) with improved cosmetic outcomes. This study aimed to explore the safety and efficacy of TOETVA in patients with PTC. MATERIALS AND METHODS: This retrospective study included TOETVA patients from Yantai Yuhuangding and Xiamen Zhongshan Hospitals. Among the 297 patients studied, 84 had benign nodules (28.3%), 208 had PTC (70.0%), and five had follicular thyroid cancer (1.7%). RESULTS: The incidence of transient and permanent recurrent laryngeal nerve injury was 1.3%, while that of transient hypoparathyroidism was 1.0%. Mental nerve paraesthesia was observed in 241 cases (81.1%), while permanent mental nerve paraesthesia was noted in seven cases (2.4%). Abnormal motor function of the lower lip and chin was observed in 12 cases (4.0%). Ten of the 208 patients with PTC (4.8%) underwent total thyroidectomy (TT) and bilateral central neck dissection (CND). A mean 6.6 ± 4.1 and 10.9 ± 4.0 lymph nodes were removed in the unilateral and bilateral surgeries, respectively, with a metastasis rate of 49.0%; a mean 2.7 ± 2.3 and 3.2 ± 2.6 lymph nodes were metastatic, respectively. The parathyroid gland was inadvertently removed in 6.6% and auto-transplanted in 10.6% of patients with unilateral PTC. The non-stimulated thyroglobulin level in the TT and bilateral CND patients was below 1 ng/mL at the 6-month follow-up. CONCLUSION: TOETVA is safe in well-selected patients with unilateral PTC. However, its safety remains unclear in patients treated with TT and bilateral CND.

miR-429 suppresses cell growth and induces apoptosis of human thyroid cancer cell by targeting ZEB1.

Thyroid cancer is now the most common endocrine malignancy and the effect of miR-429 in the development of thyroid cancer still need to be further investigated. The expression level of miR-429 was quantified by qPCR in both clinical samples and cultured cell lines. MTT, flow cytometry, migration analyses and Matrigel invasion assays were conducted to test the proliferation, apoptosis, migration and invasion of MiR-429 transfection in thyroid cancer cell lines. Luciferase activity assay and western blot were conducted to detect the direct effect of miR-429 on Zinc finger E-box-binding homeobox 1 (ZEB1) expression. In this study, it was found that miR-429 was frequently decreased in thyroid cancer tissues and cell lines. Transfection of miR-429 in thyroid cancer cell lines substantially suppressed cell proliferation, migration and invasion. Besides, miR-429 up-regulation would induce apoptosis in different cell lines. ZEB1 was identified as a direct target of miR-429 and miR-429 transfection could inhibit ZEB1 by direct binding to its 3'-untranslated region (3'-UTR). In conclusion, these data indicated that miR-429 could act as a tumour suppressor miRNA and contribute to the development and progression and metastasis of thyroid cancer.