Time Kinetics and prognosis roles of calcitonin after surgery for medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated. METHODS: A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated. RESULTS: The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS. CONCLUSION: Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.

Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent. METHODS: We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment. RESULTS: In addition to the presence of BRAF mutations and RET fusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched with AFP mutations, IGH@-ext fusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor. CONCLUSIONS: Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.

Self super-resolution of optical coherence tomography images based on deep learning.

As a medical imaging modality, many researches have been devoted to improving the resolution of optical coherence tomography (OCT). We developed a deep-learning based OCT self super-resolution (OCT-SSR) pipeline to improve the axial resolution of OCT images based on the high-resolution and low-resolution spectral data collected by the OCT system. In this pipeline, the enhanced super-resolution asymmetric generative adversarial networks were built to improve the network outputs without increasing the complexity. The feasibility and effectiveness of the approach were demonstrated by experimental results on the images of the biological samples collected by the home-made spectral-domain OCT and swept-source OCT systems. More importantly, we found the sidelobes in the original images can be obviously suppressed while improving the resolution based on the OCT-SSR method, which can help to reduce pseudo-signal in OCT imaging when non-Gaussian spectra light source is used. We believe that the OCT-SSR method has broad prospects in breaking the limitation of the source bandwidth on the axial resolution of the OCT system.

The survival outcomes of prophylactic lateral neck dissection for medullary thyroid carcinoma, a retrospective cohort study.

OBJECTIVES: The purpose of this study was to evaluate the benefits of prophylactic lymph node dissection in medullary thyroid carcinoma (MTC) patients without radiographically lateral neck metastases. DESIGN: Retrospective cohort study. SETTING: Tianjin Medical University Cancer Institute and Hospital. PARTICIPANTS: Patients who underwent primary surgery for MTC between 2011 and 2019 and without structural disease of the lateral neck preoperatively. MAIN OUTCOME MEASURES: Locoregional recurrence, disease-free survival (DFS), and overall survival (OS) were examined. RESULTS: The patients were divided into two groups: the central lymph node dissection (CLND) only group and the prophylactic lateral lymph node dissection (PLND) group, which included CLND and ipsilateral lateral lymph node dissection (LLND). A total of 89 patients were included: 71 patients in the CLND group and 18 patients in the PLND group. Although there were no significant differences in age, gender, multifocality, capsule invasion or TNM stage between the two groups, the tumour size and preoperative median calcitonin levels were different. The recurrence rate was 4.2% for the CLND group and 5.6% for the PLND group (p > 0.05). DFS among the CLND and PLND groups was 95.4% and 94.4%, and OS among the groups was 100% and 94.1% (p > 0.05) at 5 years. The biochemical cure rates were similar. CONCLUSIONS: PLND in the absence of structural disease of the lateral neck preoperatively is not associated with improved survival in patients with sporadic MTC.

Surgical selection and prognostic analysis in patients with unilateral sporadic medullary thyroid carcinoma.

PURPOSE: The extent of thyroid surgery and cervical lymph node dissection of unilateral sporadic medullary thyroid carcinoma (sMTC) is still controversial, and the aim of this study was to investigate whether hemithyroidectomy was adequate as a locally curative surgery for patients with unilateral sMTC. METHODS: This study is a retrospective case series of patients with sMTC who underwent curative total thyroidectomy or hemithyroidectomy in our institution from January 2011 to December 2019. RESULTS: In total, 129 patients who met the inclusion criteria were enrolled including 49 (38.0%) patients who underwent total thyroidectomy and 80 (62.0%) patients who underwent hemithyroidectomy. About 80 (62.0%) patients achieved a biochemical cure (BC), whereas there was no significant difference between two groups in biochemical cure rate (61.2% versus 62.5%, P = 0.885). A logistic regression analysis showed a strong negative correlation between the factors of preoperative calcitonin level and pTNM stage and biochemical cure. In the log-rank test, no significant difference in OS (P = 0.314) and DFS (P = 0.409) was found between the two surgical groups. Lateral cervical lymph node metastasis and pTNM stage were significant prognostic factors affecting DFS in univariate analysis; moreover, absence of biochemical cure, tumor size ≥ 4 cm and lateral cervical lymph node metastasis were independent risk factors of unilateral sMTC patients in our analysis. CONCLUSION: For patients with unilateral sMTC, hemithyroidectomy was adequate as a locally curative surgery, because the patients underwent total thyroidectomy did not benefit more from it in the aspects of BC/OS/RFS, while the postoperative increasing incidence rate of postoperative hypocalcemia could not improve patients' quality of life.

Classification of neck tissues in OCT images by using convolutional neural network.

Identification and classification of surrounding neck tissues are very important in thyroid surgery. The advantages of optical coherence tomography (OCT), high resolution, non-invasion, and non-destruction make it have great potential in identifying different neck tissues during thyroidectomy. We studied the automatic classification for neck tissues in OCT images based on convolutional neural network in this paper. OCT images of five kinds of neck tissues were collected firstly by our home-made swept source (SS-OCT) system, and a dataset was built for neural network training. Three image classification neural networks: LeNet, VGGNet, and ResNet, were used to train and test the dataset. The impact of transfer learning on the classification of neck tissue OCT images was also studied. Through the comparison of accuracy, it was found that ResNet has the best classification accuracy among the three networks. In addition, transfer learning did not significantly improve the accuracy, but it can somewhat accelerate the convergence of the network and shorten the network training time.

Multimodal imaging with integrated auto-fluorescence and optical coherence tomography for identification of neck tissues.

We report a multimodal optical system by combining OCT with autofluorescence imaging for identifying neck tissues, which can use the advantages of large field of view and high sensitivity for identifying parathyroid glands of fluorescence imaging, and high-resolution structural imaging of OCT to confirm them and identify lymph nodes and metastatic lymph nodes at the same time. It is proven that this multimodal optical system can be used to identify different neck tissues effectively and efficiently. We think that integrated auto-fluorescence and OCT imaging have the great potential in the application of navigation and assistant diagnosis of thyroid surgery.

Assessment of the prognostic value and N1b changes of the eighth TNM/AJCC staging system for differentiated thyroid carcinoma.

BACKGROUND: The aim of this study was to evaluate the prognostic veracity for disease-specific survival (DSS) of the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in a Chinese population of patients with differentiated thyroid carcinoma (DTC) and to evaluate the impact of N1b redefinition and reclassification on prediction of survival. METHODS: A total of 569 DTC patients who underwent thyroid surgery in two Chinese hospitals were included in analysis to assess the predictive accuracy and N1b changes of TNM-8. Data from the Surveillance, Epidemiology and End Results (SEER) program were applied to validate the findings on N1b changes of TNM-8. Unadjusted DSS was calculated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to evaluate the association of stage and lymph node metastasis (LNM) status with survival. The proportion of variation explained (PVE), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were evaluated to compare model performance. RESULTS: When TNM-8 was applied, 39.7% of patients were downstaged relative to TMN-7. In comparison of TNM-7 and TMN-8, the PVE was 18.68% and 22.33%, the AIC was 704.22 and 680.50, and the BIC was 702.98 and 679.24, respectively. In 569 Chinese patients with DTC, levels I-V LNM was significantly related to poorer DSS compared with N0 and level VI LNM. Among patients aged ≥ 55 years, those with levels I-V and VII LNM had significantly worse DSS than those with N0 and Level VI LNM. In the SEER dataset, patients with levels I-V and VII LNM had significantly worse DSS compared with those with N0 and Level VI LNM, especially in older patients (age ≥ 55 years). CONCLUSIONS: TNM-8 staged a significant number of Chinese patients into lower stages and improved the accuracy of predicting DSS compared with TNM-7. However, changes in lateral LNM definition and classification of TNM-8 have a significant prognostic implication for patients with DTC, especially older patients (≥ 55 years). Our data suggest that a modified TNM staging system would be more useful for predicting mortality and determining a proper treatment strategy in patients with DTC.

Impact of major different variants of papillary thyroid microcarcinoma on the clinicopathological characteristics: the study of 1041 cases.

BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) has been increasing globally in the past few decades. PTMC does not have a distinctive morphology that results in differences in biological behavior. The aim of this study was to classify PTMCs according to the morphological features and explore the relationship with clinicopathological characteristics. Additionally, we sought to evaluate whether different variants of PTMC can be an independent predictor for lymph mode metastasis when considering other risk factors. METHODS: Between December 2014 and December 2015, 1041 PTMC cases undergoing surgical resection at Tianjin Medical University Cancer Institute and Hospital were reviewed retrospectively. Statistical analysis was performed to investigate the independent factors for lymph node metastasis in PTMC. RESULTS: Conventional variant PTMC (CPTMC), follicular variant PTMC (FPTMC), and encapsulated variant PTMC (EnPTMC) were major variants in PTMC, collectively accounting for 96.7% of the entire PTMC cohort.There were significant differences in clinicopathological characteristics among the three major variants. The frequency of aggressive parameters was significantly different among the three variants, including tumor size, minimal extrathyroidal extension (minimal ETE), and lymph node metastasis (all P < 0.05), being highest in CPTMC, lowest in EnPTMC, and intermediate in FPTMC. FPTMC (OR = 0.642, P = 0.003) and EnPTMC (OR = 0.540, P = 0.041) were independent protective factors for lymph node metastasis (LNM). In contrast, male gender (OR = 1.836, P = 0.000), age less than 45 years (OR = 1.457, P = 0.009), tumor size greater than 0.5 cm (OR = 1.453, P = 0.007), calcification (OR = 1.465, P = 0.016), minimal ETE (OR = 1.801, P = 0.001), and multifocality (OR = 1.721, P = 0.000) were independent risk factors for LNM. CONCLUSIONS: The present study demonstrates the distinct biological behaviors of the three major PTMC variants and establishes an aggressive order of CPTMC â‰« FPTMC > EnPTMC. It is necessary to take into consideration variant-related risks and other independent predictors for the determination of lymphadenectomy in patients with PTMC.

Loss of PTEN Expression Is Associated With High MicroRNA 24 Level and Poor Prognosis in Patients With Tongue Squamous Cell Carcinoma.

PURPOSE: The aim of this study was to detect the relationship between phosphatase and tensin homolog deletion on chromosome 10 (PTEN) and microRNA 24 (miR-24) and correlate PTEN expression with important clinical parameters of patients with tongue squamous cell carcinoma (TSCC). MATERIALS AND METHODS: In this retrospective case series, all TSCC patients treated at Tianjin Medical University Cancer Institute and Hospital between March 2005 and October 2011 were retrospectively reviewed. Demographic information and clinical data (histologic type, clinical stage, tumor differentiation, and so on) were collected. The miR-24 level was detected by quantitative reverse transcription-polymerase chain reaction. The PTEN level was analyzed by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. Data analyses were performed by Spearman correlation analysis, Pearson χ2 test, and paired t test. Kaplan-Meier curves, log-rank analyses, and a Cox proportional hazards model were used to evaluate the prognostic value of PTEN. RESULTS: A total of 90 patients (aged 59.4 ± 9.5 years, 53 men and 37 women) were identified. Loss of PTEN expression was detected in 27 of 90 tumors (30%)" in both occurrences [corrected]. The PTEN messenger RNA level was negatively correlated with the miR-24 level (r = -0.569, P < .01). PTEN expression also was negatively correlated with the miR-24 level (r = -0.621, P < .01). Furthermore, PTEN expression was significantly lower in cancer tissues than in adjacent normal tissues, and its expression was negatively correlated with clinical stage (P < .01) and positively correlated with differentiation (P < .05) in TSCC patients. In addition, the Kaplan-Meier curve indicated that loss of PTEN expression resulted in poor survival of TSCC patients (P < .01). Multivariate analysis indicated that PTEN expression level and clinical stage may be independent prognostic factors for TSCC patients. CONCLUSIONS: This study suggested that PTEN expression was negatively correlated with the miR-24 level in TSCC. The loss of PTEN expression may serve as a predictor of unfavorable prognosis for TSCC patients.

[Clinical and biological features of familial nonmedullary thyroid carcinoma].

OBJECTIVE: To analyze the clinical and biological features of familial nonmedullary thyroid carcinoma (FNMTC). METHODS: Clinical data of 66 FNMTC cases of 32 pedigrees was retrospectively analyzed, compared with that of 182 control cases taken randomly from the patients with sporadic papillary thyroid carcinoma (SPTC), who were diagnosed and treated in Tianjin Cancer Hospital between January 2008 and November 2012. The features of FNMTC of the first and second generations were objectively analyzed. Some data quoted from the literature were also used for the analysis. RESULTS: The median age at diagnosis of all the 66 FNMTC patients was 44 years, and 57 (86.4%) were females. Moreover, 71.2% (47 patients, 23 pedigrees) of the FNMTC patients exhibited a sibling relationship, and 28.8% (19 patients, 9 pedigrees) of the FNMTC patients exhibited a parent-offspring relationship, and 9 cases in the first generation and 10 cases in the second generation. There were significant differences between the FNMTC group and SPTC group in terms of tumor multicentricity, tumor bilaterality, lymph node metastasis, central lymph node metastasis, concomitant chronic thyroiditis and recurrence (P < 0.05). Compared with SPTC, sibling FNMTC presented a higher rate of central lymph node metastasis, while parent-offspring FNMTC showed frequent tumor bilaterality and a higher rate of recurrence (P < 0.05). Besides, patients in the second generation were diagnosed at an earlier age and had a higher male rate, the tumors were more frequently multifocal and bilateral, and had a higher rate of lymph node metastasis. CONCLUSIONS: FNMTC may be more aggressive than SPTC and patients in the second generation may exhibit the "anticipation" phenomenon. It's necessary to make sufficient detailed interrogation and long-term follow-up of the patients and their family for providing individual recommendations for clinical management.

Enhancement of OCTen faceimages by unsupervised deep learning.

Objective. The quality of optical coherence tomography (OCT)en faceimages is crucial for clinical visualization of early disease. As a three dimensional and coherent imaging, defocus and speckle noise are inevitable, which seriously affect evaluation of microstructure of bio-samples in OCT images. The deep learning has demonstrated great potential in OCT refocusing and denoising, but it is limited by the difficulty of sufficient paired training data. This work aims to develop an unsupervised method to enhance the quality of OCTen faceimages.Approach. We proposed an unsupervised deep learning-based pipeline. The unregistered defocused conventional OCT images and focused speckle-free OCT images were collected by a home-made speckle modulating OCT system to construct the dataset. The image enhancement model was trained with the cycle training strategy. Finally, the speckle noise and defocus were both effectively improved.Main results. The experimental results on complex bio-samples indicated that the proposed method is effective and generalized in enhancing the quality of OCTen faceimages.Significance. The proposed unsupervised deep learning method helps to reduce the complexity of data construction, which is conducive to practical applications in OCT bio-sample imaging.

Analysis of Surgical Outcomes in Endoscopic-Assisted Lateral Neck Dissection.

BACKGROUND: Currently, endoscopic-assisted lateral neck dissection (EALND) is performed to reduce postoperative scarring of the anterior neck. This study aimed to compare surgical outcomes between EALND and conventional open lateral neck dissection (COLND) for papillary thyroid carcinoma (PTC) with lateral lymph node metastases (LNM). METHODS: The study reviewed 103 PTC patients who were classified on the basis of surgical type and statistically compared using propensity score matching analysis. RESULTS: The mean operation time is longer, and the cost of surgery is higher in the EALND group than COLND group (all p < 0.05). The numbers of retrieved and positive level II LNs, the rate of level II LNs detection between two groups do not differ significantly (all p > 0.05). The incidence of postoperative neck numbness is lower, and patients are more satisfied with postoperative neck scarring in the EALND group than COLND group (all p < 0.05). The common complications of two groups are transient recurrent laryngeal nerve injury and transient hypoparathyroidism. CONCLUSIONS: EALND is safe and feasible compared with COLND. The incision is more aesthetically satisfactory, which makes EALND a surgical approach for PTC patients with lateral LNM. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2221-2227, 2024.

Changes of biochemical factors and the effect on recurrence of medullary thyroid carcinoma after surgery.

Objective: Medullary thyroid carcinoma (MTC) is a rare malignancy secreting calcitonin (Ctn). We aimed to analyze the relationship between Ctn levels at different time points in patients with MTC, and evaluate its predictive effect on recurrence. Methods: A retrospective study of patients diagnosed with MTC in a large medical center were conducted in northern China. The interrelationships between preoperative Ctn, normalization of postoperative serum Ctn at the first month (NPS), and long-term biochemical cure as well as their predicting roles on structural recurrence were assessed. Results: A total of 212 patients were included in this study. The median follow-up time was 59.5 months. The 5- and 10-year cumulative disease-free survival rates were 81.5 % and 66.8 %, respectively. NPS (OR: 216.33, 95 % CI: 28.69-1631.09, P < 0.001) and absence of structural recurrence (OR: 61.71, 95 % CI: 3.90-975.31; P = 0.003) were associated with biochemical cure. Non-biochemical cure (OR: 28.76; 95 % CI: 2.84-290.86; P = 0.004, HR: 14.63, 95 % CI: 2.27-94.07, P = 0.005), larger tumor size (OR: 8.79, 95 % CI: 2.12-36.40, P = 0.003, HR: 5.41, 95 % CI: 2.04-14.37, P = 0.001), and multifocality (OR: 4.02, 95 % CI: 1.06-15.17, P = 0.040, HR: 3.00, 95 % CI: 1.18-7.60, P = 0.021) were unfavorable independent predictors of structural recurrence and disease-free survival. For sporadic MTC confined to the thyroid lobe, there was no difference in biochemical or structural prognosis between the different surgeries in the subgroup analysis. Conclusions: NPS, rather than preoperative Ctn, predicted long-term biochemical cure for MTC. Non-biochemical cure, larger tumor burden including larger tumor size and multifocality at initial surgery, served as worse prognostic predictors.

SETMAR Facilitates the Differentiation of Thyroid Cancer by Regulating SMARCA2-Mediated Chromatin Remodeling.

Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial-mesenchymal transformation (EMT), thyroid differentiation-related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor-based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. Finally, the METTL3-14-WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR-SMARCA2-TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.

Value of lymph node ratio as a prognostic factor of recurrence in medullary thyroid cancer.

Background and Objectives: The purpose of this study is to evaluate the relationship between lymph node status (the number of resected lymph nodes; the number of metastatic lymph nodes, LNM, and lymph node ratio, LNR) and biochemical recurrence, disease-free survival (DFS), as well as overall survival (OS) in medullary thyroid carcinoma (MTC). Methods: This study enrolled MTC patients at Tianjin Medical University Cancer Institute and Hospital between 2011 and 2019. We used Logistic regression analysis, Cox regression models and Kaplan-Meier test to identify risk factors influencing biochemical recurrence, DFS, and OS. Results: We identified 160 patients who satisfied the inclusion criteria from 2011 to 2019. We used ROC analysis to define the cut-off value of LNR with 0.24. Multifocality, preoperative calcitonin levels, pathologic N stage, resected lymph nodes, LNM, LNR, and the American Joint Committee on Cancer (AJCC) clinical stage were significant (P < 0.05) prognostic factors influencing biochemical cure. In univariable analyses, gross extrathyroidal extension, preoperative calcitonin levels, pathologic T classification, pathologic N stage, resected lymph nodes, LNM, LNR, AJCC clinical stage, and biochemical cure were significant (P < 0.05) factors of DFS. When the multivariable analysis was performed, LNR was identified as predictor of DFS (HR = 4.818, 95% CI [1.270-18.276]). Univariable Cox regression models reflected that tumor size, pathologic N stage, and LNR were predictor of OS. Furthermore, multivariable analysis manifested that LNR was predictor of OS (HR = 10.061, 95% CI [1.222-82.841]). Conclusions: This study illustrated that LNR was independent prognostic factor of DFS and OS in MTC. In addition, LNR influenced biochemical cure. Further investigations are needed to determine the optimal cut-off value for predicting prognosis.

Safety and effectiveness of carbon nanoparticles suspension-guided lymph node dissection during thyroidectomy in patients with thyroid papillary cancer: a prospective, multicenter, randomized, blank-controlled trial.

Objective: This study aimed to evaluate the effectiveness and safety of carbon nanoparticles-guided lymph node dissection during thyroidectomy in patients with papillary thyroid cancer(PTC). Methods: Clinical trials consisted of two subgroups: unilateral lobectomy (UL; n=283) and total thyroidectomy (TT; n=286). From each subgroup, the patients were randomly assigned to two groups: the carbon nanoparticle group and control group. Primary endpoints included parathyroid hormone (PTH) levels, number of lymph nodes (LNs) detected, number of tiny lymph nodes detected, and recognition and retention of the parathyroid glands. Secondary endpoint was recognition and protection of the recurrent laryngeal nerve. Results: A total of 569 patients with PTC were recruited. There were no statistically significant differences in demographics between the carbon nanoparticles and control groups (P > 0.05). In the UL subgroup, there were no significant differences in PTH levels between the two groups at preoperative, intraoperative, and postoperative day one, and postoperative month one (P>0.05). There was no significant difference in the serum Ca2+ levels between the two groups preoperatively and at postoperative month one (P>0.05). The number of lymph nodes dissected in the carbon nanoparticles group was significantly higher than that in the control group (P<0.0001). The detection rate of tiny lymph nodes in the carbon nanoparticles group was higher than that in the control group (P=0.0268). In the TT subgroup, there was no significant difference in PTH levels between the two groups at preoperative, intraoperative, and postoperative day one (P>0.05). However, the mean PTH level in the carbon nanoparticles group was significantly higher than that of the control group at postoperative month one (P=0.0368). There was no significant difference in the serum Ca2+ levels between the two groups preoperatively and at postoperative month one (P>0.05). There were no significant differences between the two groups in the number of dissected LNs (P>0.05) or the detection rate of tiny lymph nodes (P>0.05). No drug-related AE and complications due to the injection of carbon nanoparticles were recorded in this study. There were no significant differences between the two groups in terms of parathyroid preserved in situ and recurrent laryngeal nerve injury in the UL and TT subgroups. Conclusions: Carbon nanoparticles demonstrated efficacy and safety in thyroidectomy. The application of carbon nanoparticles could significantly facilitate the identification and clearance of LNs and the optimum preservation of parathyroid function. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300068502.

PARP inhibitor shuts down the global translation of thyroid cancer through promoting Pol II binding to DIMT1 pause.

Thyroid cancer has become the most frequent endocrine-related malignancy. Currently, a mounting body of evidences support the clinical strategies for extending the benefit of PARP inhibitors beyond BRCA-mutant cancers. However, the functions and molecular mechanisms of PARP inhibitors in thyroid cancers (TCs) are not fully understood. Here, on the one hand, we revealed that niraparib promotes the accumulation of DNA damage in TCs. On the other hand, we indicated that niraparib inhibits the transcription of DIMT1 through promoting Pol II pausing in a PAR-dependent manner, subsequently leading to a global translation inhibition in TCs. Meanwhile, we found that niraparib activates the NF-κB signaling pathway by inhibiting the PARylation of p65, which decreases its ubiquitination and degradation level through E3 ubiquitin ligase RNF146. Moreover, bortezomib (a small molecule inhibitor of the NF-κB signaling pathway) could significantly enhance the anti-tumor effect of niraparib on TCs in vitro and in vivo. Our findings provide mechanistic supports for the efficacy of PARP inhibitors in cancer cells lacking BRCA-mutant.

Digital refocusing based on deep learning in optical coherence tomography.

We present a deep learning-based digital refocusing approach to extend depth of focus for optical coherence tomography (OCT) in this paper. We built pixel-level registered pairs of en face low-resolution (LR) and high-resolution (HR) OCT images based on experimental data and introduced the receptive field block into the generative adversarial networks to learn the complex mapping relationship between LR-HR image pairs. It was demonstrated by results of phantom and biological samples that the lateral resolutions of OCT images were improved in a large imaging depth clearly. We firmly believe deep learning methods have broad prospects in optimizing OCT imaging.

Relationship Between Thyroid Autoantibodies and Recurrence of Papillary Thyroid Carcinoma in Children and Adolescents.

Background: Numerous studies reported connection between papillary thyroid carcinoma (PTC) and thyroid autoantibody in adults, but few of them have investigated whether there is a similar link in children and adolescents. The purpose of this research was to explore the relationship between clinicopathological features, prognosis and preoperative thyroid peroxidase antibody (TPOAb) as well as thyroglobulin antibody (TgAb) status in children and adolescents with PTC. Methods: This study retrospectively reviewed 179 patients of PTC who underwent a thyroidectomy from January 2000 to June 2021 at Tianjin Medical University Cancer Hospital. We compared preoperative TgAb and TPOAb status with the clinicopathological features and prognosis of children and adolescents with PTC in different age groups. Results: Patients with positive preoperative TPOAb and TgAb had lower recurrence rate in the younger group (P = 0.006, 0.047, respectively). Patients with positive TPOAb preoperatively had normal level of preoperative Tg and less cervical LNM than patients with negative TPOAb in children and adolescents (P < 0.05). Positive TPOAb preoperatively of PTC patients had a longer median DFS (113.4 months) than negative TPOAb (64.9 months) (P = 0.009, log-rank). Univariate analyses showed age, maximal tumor size, T stage, multifocality, lateral LNM and N staging were predictors for cancer recurrence in children and adolescents (P<0.05). Cox regression analysis found younger age (HR 0.224, P < 0.001), lateral LNM (HR 0.137, P = 0.010), N stage (HR 30.356, P < 0.001) were independent risk factors for recurrence. Conclusions: Our study found that presence of preoperative TPOAb and TgAb could serve as novel prognostic factors for predicting recurrence of PTC in children.