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Purpose To evaluate the effect of Hashimoto's thyroiditis (HT) on the extent of ablation zone in ultrasound (US)-guided radiofrequency ablation (RFA) for early stages of papillary thyroid microcarcinoma (PTMC). Method We selected 772 patients with 797 PTMCs who underwent with RFA from August 2017 to August 2020. They were subdivided into two groups as follows: (i) 216 patients (224 PTMCs) with HT in the ‘HT + PTMC’ group and (ii) 556 patients (573 PTMCs) with healthy thyroid in the ‘PTMC’ group. We assessed the extent (maximum diameter and volume) of the ablation zone by contrast-enhanced ultrasound (CEUS) immediately, one day, and 1 week following RFA. Results The ablation zone of the ‘HT + PTMC’ group was smaller than that of the ‘PTMC’ group at 1 week of RFA (maximum diameter: 14.6 ± 3.1 mm vs. 15.2 ± 3.2 mm and volume: 0.932 ± 0.498 mL vs. 1.028 ± 0.540 mL, respectively, p .05). Life-threatening complications did not develop in any of the patients. Conclusion RFA-treated PTMCs were smaller in size in patients with HT than in those with a healthy thyroid at 1 week of RFA. However, the exact mechanism underlying this phenomenon and its clinical significance warrant further investigation.

Background We comprehensively evaluate the efficacy and safety of US-guided radiofrequency ablation (RFA) in the treatment of papillary thyroid microcarcinoma (PTMC) via a systematic review and meta-analysis.Methods We searched the PubMed, Embase and Cochrane Library databases for studies published during the time between the establishment of the database through October 2021. We included a 10 non-randomized controlled trial (non-RCT) that reported the application of US-guided RFA in PTMC. The sample size of patients totaled 1279. We evaluated the ablation efficacy by analyzing the volume reduction rate (VRR), complete disappearance rate (CDR) and recurrence rate of PTMC treated by RFA. We analyzed all data using STATA version 15.1 (Stata Corporation, College Station, TX).Results Our pooled results proved RFA treatment significantly reduces the volume of tumors (Weighted Mean Difference [WMD] = −103.20, 95% CI: −111.93 – −94.48, p = 0.000). We also found the VRR at 12 months after RFA was 93.27% (95% CI: 84.68–101.86), and the CDR at 12 months after RFA was 64% (95% CI: 39–89%). Additionally, pooled results showed the incidence of mPTC residue in ablation area, newly discovered mPTC and lymph node metastases after RFA treatment were respectively 0.3% (95% CI: −0.1–0.7%), 2.5% (95% CI: 1.1–3.9%) and 1.0% (95% CI: 0.2–1.9%), and the incidence of complications after RFA treatment was 1.8% (95% CI: 0.7–3.2%).Conclusions US-guided RFA is effective and safe for treating PTMC. It could be an excellent alternative to the existing treatment options.

Xue Huang,1,* Yukun Zhang,1,* Du He,1 Lin Lai,1 Jun Chen,1 Tao Zhang,2 Huilin Mao2 1Department of Medical Oncology, Enshi Tujia and Miao Autonomous Prefecture Central Hospital, Enshi, 445000, People’s Republic of China; 2Department of Pediatric Surgery, Enshi Tujia and Miao Autonomous Prefecture Central Hospital, Enshi, 445000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao Zhang, Department of Pediatric Surgery, Enshi Tujia and Miao Autonomous Prefecture Central Hospital, No. 158 Wuyang Avenue, Enshi, People’s Republic of China, Email taozhang870214@163.com Huilin Mao, Enshi Tujia, and Miao Autonomous Prefecture, Enshi, Hubei Province, 445000, People’s Republic of China, Email maohuilin2022@163.comPurpose: Although many factors determine the prognosis of papillary thyroid carcinoma (PTC), cervical lymph node metastasis (CLNM) is one of the most terrible factors. In view of this, this study aimed to build a CLNM prediction model for papillary thyroid microcarcinoma (PTMC) with the help of machine learning algorithm.Methods: We retrospectively analyzed 387 PTMC patients hospitalized in the Department of Medical Oncology, Enshi Tujia and Miao Autonomous Prefecture Central Hospital from January 1, 2015, to January 31, 2022. Based on supervised learning algorithms, namely random forest classifier (RFC), artificial neural network(ANN), support vector machine(SVM), decision tree(DT), and extreme gradient boosting gradient(XGboost) algorithm, the LNM prediction model was constructed, and the prediction efficiency of ML-based model was evaluated via receiver operating characteristic curve(ROC) and decision curve analysis(DCA).Results: Finally, a total of 24 baseline variables were included in the supervised learning algorithm. According to the iterative analysis results, the pulsatility index(PI), resistance index(RI), peak systolic blood flow velocity(PSBV), systolic acceleration time(SAT), and shear wave elastography elastic index(SWEEI), such as average value(Emean), maximum value(Emax), and minimum value(Emix) were candidate predictors. Among the five supervised learning models, RFC had the strongest prediction efficiency with area under curve(AUC) of 0.889 (95% CI: 0.838– 0.940) and 0.878 (95% CI: 0.821– 0.935) in the training set and testing set, respectively. While ANN, DT, SVM and XGboost had prediction efficiency between 0.767 (95% CI: 0.716– 0.818) and 0.854 (95% CI: 0.803– 0.905) in the training set, and ranged from 0.762 (95% CI: 0.705– 0.819) to 0.861 (95% CI: 0.804– 0.918) in the testing set.Conclusion: We have successfully constructed an ML-based prediction model, which can accurately classify the LNM risk of patients with PTMC. In particular, the RFC model can help tailor clinical decisions of treatment and surveillance.Keywords: papillary thyroid microcarcinoma, cervical lymph node metastasis, shear wave elastography elastic index, machine learning algorithm, prediction model

Ting Wu, Guo-Qing Sui, Deng-Ke Teng, Qiang Luo, Hui Wang, Yuan-Qiang Lin Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of ChinaCorrespondence: Hui Wang; Yuan-Qiang Lin, Tel +86-431-84995070 ; +86-15948309530, Email whui66@jlu.edu.cn; linyuanqiang@jlu.edu.cnBackground: In recent years, papillary thyroid microcarcinoma (PTMC) has been a main cause of the high incidence of thyroid carcinoma. No existing study has reported whether microwave ablation (MWA) affects patients’ immunity. Therefore, this study explored the effects of MWA treatment on the immune functions of patients with PTMC.Methods: This study included 50 patients diagnosed with PTMC who received MWA treatment under ultrasound guidance at the ultrasound department of our hospital from January 2019 to October 2020. Changes in immune function after MWA treatment in PTMC patients were detected by T lymphocyte subsets and cytokines secreted by T helper cells.Results: At 1 day and 2 weeks after MWA treatment, the proportions of CD3+, CD4+ and CD4+/CD8+ T lymphocyte subsets and the levels of the cytokines interleukin (IL)-2 and interferon (IFN)-γ in the peripheral blood of the patients were significantly higher than those before MWA treatment (P< 0.05). The levels of CD8+ T lymphocytes, tumour necrosis factor (TNF)-α, IL-4, IL-6, IL-10 and IL-17A were not significantly different from those before MWA treatment (P> 0.05). One month after MWA treatment, the proportions of CD3+, CD4+, CD8+ and CD4+/CD8+ T lymphocytes and the levels of the cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α and IL-17A were not significantly different from those before MWA treatment (P> 0.05).Conclusion: The immune functions of patients with PTMC are temporarily enhanced after MWA treatment, which has important clinical significance for patients’ anti-PTMC ability.Keywords: microwave ablation, papillary thyroid microcarcinoma, T lymphocyte, cytokine

Background: To investigate the effect of central lymph node dissection on the prognosis of patients with papillary thyroid microcarcinoma (PTMC) without clinical lymph node metastasis (cN0). Methods: According to the inclusion and exclusion criteria, 462 patients with cN0 PTMC underwent surgery in the Second Department of General Surgery, Zhongshan City People’s Hospital from January 1, 2007, to June 31, 2017. They were divided into two groups: the undissection group (262 cases) and the dissection group (170 cases). A comparison was made between the two groups in terms of postoperative complications, recurrences, metastases, etc., as well aslymph node metastasis risk factors in the central region of cN0 PTMC. Results: There was no lymphatic leakage or death in all patients after the operation. In the dissection group, 64 cases (37.6%) of central lymph node metastasis were found after the postoperative pathological examination. The undissection group was followed up for (92 ± 28.7) months, and the dissection group was followed up for (86 ± 25.4) months (t=-2.165, P = 0.031). In the two groups, there were no lung metastases, bone metastases, or other distant metastases during the follow-up period. In the undissection group, there were 7 cases, while in the dissection group, there were just 2. Recurrence rates between the two groups did not differ significantly (χ2 = 0.126, P = 0.169); Similarly, disease-free survival curves did not differ significantly (χ2 = 2.565, P = 0.708). Hypoparathyroidism and Hypocalcemia also had no difference between the group. In comparison to the undissection group, the capsular invasion rate (P = 0.026), calcification rate(P < 0.001) incidence of postoperative hoarseness (P = 0.017), and hand and foot numbness rate (P < 0.001) were all considerably greater in the dissection group. Multivariate research revealed that capsular invasion (OR = 9.42, P = 0.002), multifocal (OR = 24.57, P < 0.001), and tumor diameter > 5 mm (OR = 5.46, P = 0.019) were the independent risk factors for central lymph node metastasis in cN0 PTMC. Conclusions: Thyroidectomy alone is safe for cN0 PTMC, but longer-term follow-up is still required for changes in central lymph nodes. For cN0 PTMC patients with tumor diameter > 5 mm, multifocal, and capsular invasion, central lymph node metastasis is more likely to occur. Comprehensive evaluation and individualized and precise treatment are essential. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively compare the clinical efficacy of transoral oral vestibular approach and transthoracic breast approach in the treatment of papillary thyroid microcarcinoma (PTMC). Methods: The clinical data of 141 patients with unilateral PTMC who were admitted to Department of Thyroid and Vascular Surgery, Nanhai Hospital Affiliated to Southern Medical University from January 2019 to June 2021 were retrospectively analyzed. The patients were divided into group A ( n = 83 transthoracic breast approach) and group B (n=58, transoral oral vestibular approach) according to the different approaches. The operation-related indicators, traumatic stress indicators, cosmetic satisfaction, complications and follow-up prognosis were compared in the two groups. Results: The operation time in the group B was longer than that in the group A, the number of central lymph nodes dissected was more than that in the group A, the drainage volume on 1 d after operation and intraoperative blood loss were less than those in the group A, the neck VAS score on 1 d after operation and the total length of incision were less than those in the group A, and the postoperative hospital stay was shorter than that in the group A (P < 0.05) . There were no significant differences in white blood cell count (WBC), C-reactive protein (CRP), prostaglandin E2(PGE) and cortisol (Cor) between the two groups before operation and 2 d after operation (P > 0.05) . 0.2d after operation, the levels of WBC, PGE2, CRP and Cor in the two groups were significantly higher than those before operation, and the differences were statistically significant (P < 0.05) . The cosmetic satisfaction rate in the group B was higher than that in the group A ( p < 0 . 05). There was no difference in the incidence of complications in the two groups (P>0.05). At 1-year postoperative follow-up, the rates of death, recurrence, and cervical lymph node metastasis were 0 in both groups, with no differences between the two groups (P > 0.05) Conclusion: Transoral oral vestibular approach can achieve the same surgical effect as transthoracic breast approach in the treatment of PTMC. However, transoral oral vestibular approach removes more central lymph nodes, has less trauma, less postoperative pain, and has a higher cosmetic satisfaction. [ABSTRACT FROM AUTHOR]

Objective: To report more than 5-year outcomes of ultrasound-guided thermal ablation (TA) for patients with solitary low-risk papillary thyroid microcarcinoma (PTMC) in a large multicenter cohort. Background: TA, including radiofrequency ablation (RFA) and microwave ablation (MWA) have been used in patients with low-risk PTMC who refuse surgery or active surveillance. However, its clinical value remains controversial. Materials and Methods: This retrospective multicenter study included 474 patients with solitary low-risk PTMC treated with TA (357 for RFA; 117 for MWA) from 4 centers and followed up for at least 5 years. Disease progression including lymph node metastasis and recurrent tumors, volume reduction rate (VRR), tumor disappearance rate, complications, and delayed surgery were assessed. RFA and MWA outcomes were compared using propensity score matching. Results: During the median follow-up period of 77.2 months, disease progression incidence, lymph node metastasis, and recurrent tumors rates were 3.6%, 1.1%, and 2.5%, respectively. Age below 40 years old, male sex, Hashimoto thyroiditis, and tumor size were not independent factors associated with disease progression by Cox analysis. The median VRR was 100% and 471 tumors disappeared radiographically. Eight patients experienced transient voice change (1.7%) which recovered within 3 months. None of the patients underwent delayed surgery because of anxiety. After 1:1 matching, no significant differences were found in the disease progression, VRR, tumor disappearance rate, or complications between RFA and MWA subgroups. Conclusion: This multicenter study revealed that TA was an effective and safe treatment for patients with solitary low-risk PTMC, which could be offered as a treatment option for the management for low-risk PTMC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis (LNM) is prevalent in papillary thyroid microcarcinoma (PTMC) and is essential when determining tumor stage and prognosis. Positive lateral LNM with negative central LNM is defined as skip metastasis. Thyroid carcinoma's risk factors for skip metastasis remain controversial, especially in PTMC. This study aimed to determine the clinical features as well as the risk factors of skip metastasis among patients with PTMC. Methods: We conducted retrospective research among patients with PTMC who were subjected to treatment at our Hospital between January 2018 and December 2019 by reviewing their medical records. A database containing demographic characteristics, ultrasonography features, blood test outcomes, operation information, pathology details, and follow‐up information was constructed. The link between skip metastasis and clinicopathological features of PTMC was evaluated using univariate as well as multivariate analyses. Results: Overall, 293 patients diagnosed with PTMC and lateral LNM were included. There were 91 men (31.1%) and 202 women (68.9%). The median age was 38 (31–47) years. Fifty patients were diagnosed with skip metastases. Levels III and II + III were the most prevalent in single‐level and two‐level metastasis, correspondingly. Univariate and multivariate analyses detected two independent factors linked to skip metastasis in PTMC: female sex (odds ratio = 2.609, 95% confidence interval (CI): 1.135–6.000; p = 0.024) and location of the tumor (upper portion) (odds ratio = 2.959, 95% CI: 1.552–5.639; p = 0.001). Conclusions: Skip metastasis is prevalent in thyroid carcinoma. Female sex and tumor location (upper portion) are independently linked to skip metastasis in PTMC. Patients who have these two risk factors should undergo a meticulous preoperative and intraoperative evaluation of lymph node status. [ABSTRACT FROM AUTHOR]

The detection of low-risk thyroid carcinoma has increased in recent decades, although disease-specific mortality remained without changes. The high prevalence of occult carcinomas in autopsy studies, and hence the underlying indolent course of this entity, prompted the emergence of active surveillance as an alternative approach to these tumors. This strategy aims to recognize the minority group of patients who will develop clinical progression and probably benefit from deferred surgery. Experience around the world has shown that during active surveillance these tumors are mostly unchanged in size, with very-slow growth and even a decrease in diameter. Moreover, the rates of lymph node metastases were low and easily handled by rescue surgery, and distant metastases have not been reported. Given the high prevalence of small thyroid carcinomas and the excellent outcomes for observation, active surveillance provides a safe and feasible alternative in properly selected patients with low-risk thyroid cancer. [ABSTRACT FROM AUTHOR]

Objective: Thyroidectomy is the first‐line treatment for papillary thyroid microcarcinoma (PTMC), but often involves aggressive overtreatment. Thermal ablation (TA) has been gradually used for the treatment of recurrent PTMC. However, it is not recommended for the treatment of primary PTMC according to the Korean and Italian guidelines. Therefore, this systematic review aimed to analyse the indications, efficacy, and safety of TA in the treatment of PTMC. Design: Systematic review. Patients and Measurements: A search strategy was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. A total of 27 articles were included in this study until January 2022. Results: According to current guidelines and studies, we divided the indications of TA for PTMC into six primary and three secondary indications. Laser ablation (LA) has the advantages of a small needle, accurate output energy and precision ablation, and it is safe to important organs around the lesion. The patients recover quickly after radiofrequency ablation (RFA), with no major complications, recurrence, or lymph node metastasis. The volume reduction rate after RFA was the highest, followed by microwave ablation and LA, and the improvement in patient quality of life after TA was significantly better than after thyroidectomy. Conclusions: TA is an effective alternative method for surgery in the treatment of low‐risk PTMC and has the advantages of being minimally invasive, economical, having less bleeding and having a high postoperative quality of life. [ABSTRACT FROM AUTHOR]

Background: The incidence of papillary thyroid microcarcinoma (PTMC) has increased rapidly in recent decades, with a favorable overall prognosis. We aimed to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treating low-risk PTMC in Taiwan. Methods: This prospective study included patients with PTMC who were ineligible or refused surgery and underwent US-guided RFA between October 2018 and June 2020. US and computed tomography (CT) were performed before RFA to assess tumor lesions and exclude cervical lymph node metastasis. Sequential US follow-up following RFA was performed after 1, 3, 6, and 12 months, and yearly thereafter. Volume reduction ratio (VRR) and complete disappearance rate of tumor at one year were evaluated. Results: 13 PTMCs in 12 patients were enrolled with a mean follow-up of 16.2 ± 8.1 months (range, 1–24 months). The median largest tumor diameter and tumor volume before RFA were 0.76 cm and 0.15 ml (range, 0.02–0.37 ml). The median (interquartile range, IQR) volume and VRR at 12 months post-RFA were 0 (0, 0.03) ml (p = 0.033) and 100% (84.26%, 100%) (p = 0.008). Eight tumors (61.54%) were completely disappeared at 12 months post-RFA and no tumor recurrence, lymph nodes, or distant metastasis were noted. All tumors were successfully treated without complications. Conclusion: Minimally invasive US-guided RFA is an effective and safe alternative for low-risk PTMC, resulting a satisfied VRR.

Non-invasive biomarkers for the diagnosis and prognosis of papillary thyroid microcarcinoma (PTMC) are still urgently needed. We aimed to characterize the N-glycome of PTMC, and establish nomograms for the diagnosis of PTMC and the prediction of lymph node metastasis (LNM). N-glycome of PTMC (LNM vs. non-LNM, capsular invasion (CI) vs. non-CI (NCI)) and matched healthy controls (HC) were quantitatively analyzed based on mass spectrometry. N-glycan traits associated with PTMC/LNM were used to create binomial logistic regression models and were visualized as nomograms. We found serum N-glycome differed between PTMC and HC in high-mannose, complexity, fucosylation, and bisection, of which, four N-glycan traits (TM, CA1, CA4, and A2Fa) were significantly associated with PTMC. The nomogram based on four traits achieved good performance for the identification of PTMC. Two N-glycan traits (CA4 and A2F0S0G) showed strong associations with LNM. The nomogram based on two traits showed relatively good performance in predicting LNM. We also found differences between CI and NCI in several N-glycan traits, which were not the same as that associated with LNM. This study reported serum N-glycosylation signatures of PTMC for the first time. Nomograms constructed from aberrant glycans could be useful tools for PTMC diagnosis and stratification.

Purpose To identify candidate factors for predicting high-volume lateral lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC). Methods We retrospectively studied 2981 patients with PTMC who underwent thyroidectomy from 2013 to 2016. LLNM was identified by histopathology. Patients with different LLNM statuses were compared according to clinical, sonographic and pathological parameters. A multivariate logistic model was established to predict high-volume LLNM (number of metastatic lymph nodes >5). Results High-volume LLNM of PTMC was independently associated with age < 40 years (OR = 1.791, P = 0.023), male sex (OR = 2.401, p = 0.001), tumor size > 0.5 cm (OR = 4.839, p 0.5 cm, extrathyroidal extension and microcalcification were relatively higher than those without. These findings may be useful for identifying patients at higher high-volume LLNM risk who may require more aggressive treatment or intensive follow-up management.

Abstract Background To investigate the diagnostic value of ultrasound gray scale ratio (UGSR) in differentiating papillary thyroid microcarcinomas (PTMCs) from benign micronodules (BMNs) in patients with Hashimoto’s thyroiditis (HT). Methods The ultrasound images of 285 PTMCs (from 247 patients) and 173 BMNs (from 140 patients) in the HT group, as well as 461 PTMCs (from 417 patients) and 234 BMNs (from 197 patients) in the non-HT group were retrospectively analyzed. The diagnosis of all cases was confirmed by histopathological examinations. The gray scale values of the nodules and surrounding thyroid tissues were measured and subsequently the UGSRs were calculated. Receiver operating characteristic curve analysis was used to determine the area under the curve (AUC), optimal UGSR threshold, sensitivity and specificity in differentiating PTMCs and BMNs in the two groups. Results The UGSR of PTMC and BMN was 0.52 ± 0.12 and 0.85 ± 0.24 in the HT group (P

Abstract Introduction Central lymph node status in papillary thyroid microcarcinoma (PTMC) plays an important role in treatment decision-making clinically, however, it is not easy to predict central lymph node metastasis (CLNM). The present work focused on finding the more rational alternative for evaluating central lymph node status while identifying influencing factors to construct a model to predict CLNM incidence. Methods In this study, we retrospectively analyzed the typical sonographic and clinicopathologic features of 546 PTMC patients who underwent surgery, among which, the data of 382 patients were recruited in the training cohort and that of 164 patients in the validation cohort. Based on the outcome of the training cohort, significant influencing factors were further identified through univariate analysis and were considered as independent variables in multivariable logistic regression analysis and incorporated in and presented with a nomogram. Results In total, six independent predictors, including the age, sex, tumor size, multifocality, capsular invasion, Hashimotos thyroiditis were entered into the nomogram. Both internal validation and external validation revealed the favorable discrimination of our as-constructed nomogram. Calibration curves exhibited high consistency. As suggested by decision-curve analyses, the as-constructed nomogram might be applied in clinic. Besides, the model also distinguished patients according to risk stratification. Conclusions The novel nomogram containing remarkable influencing factors for CLNM cases was established in the present work. The nomogram can assist clinicians in clinical decision-making.

Purpose: To compare the cost-benefit of active surveillance (AS) against immediate fine needle aspiration (FNA) of sonographically suspicious sub-centimeter thyroid nodules.Methods: A Markov model was constructed to compare the cost-benefit of three strategies from point of discovery till death: 1) Surveillance of All Nodules; 2) Surveillance of Nodules with Positive Cytology; and 3) Surgery of Nodules with Positive Cytology. The reference case was a 40 year-old female with a sonographically suspicious sub-centimeter thyroid nodule. Transition probabilities, costs, and health utilities were derived from the literature. Sensitivity analyses were performed to evaluate model uncertainty. Willingness-to-pay threshold was set at $100,000/quality-adjusted life year (QALY).Results: Surveillance of Nodules with Positive Cytology dominated in the reference scenario, and was cost-beneficial over Surveillance of All Nodules independent of the utility of AS. Surveillance of All Nodules was cost-beneficial only at life expectancy <2.6 years or surveillance duration <4 years.Conclusion: While current guidelines recommend AS of sonographically suspicious sub-centimeter nodules, this study's results suggest immediate FNA (Surveillance of Nodules with Positive Cytology) is more cost-beneficial compared to AS (Surveillance of All Nodules). Patients with positive cytology on FNA may subsequently opt for AS (Surveillance of Nodules with Positive Cytology) or surgery (Surgery of Nodules with Positive Cytology) according to their level of comfort (i.e. utility) with AS. [ABSTRACT FROM AUTHOR]

Background: The frequency of thyroid cancer has rapidly increased in recent years globally. Thus, more papillary thyroid microcarcinoma (PTMC) patients are being diagnosed, including clinical lymph node-negative (cN0) patients. Our study attempted to develop a prediction model for assessing the probability of central lymph node metastasis (CLNM) in cN0 PTMC patients. Methods: A total of 595 patients from the Affiliated Hospital of Qingdao University (training cohort: 456 patients) and the Affiliated Hospital of Jining Medical University (verification cohort: 139 patients) who underwent thyroid surgery between January 2020 and May 2022 were enrolled in this study. Their clinical and molecular pathology data were analyzed with multivariate logistic regression to identify independent factors, and then we established a prediction model to assess the risk of CLNM in cN0 PTMC patients. Results: Multivariate logistic regression analysis revealed that sex, Hashimoto's thyroiditis (HT), tumor size, extrathyroidal extension, TERT promoter mutations and NRAS mutation were independent factors of CLNM. The prediction model demonstrated good discrimination ability (C-index: 0.757 and 0.753 in the derivation and validation cohorts, respectively). The calibration curve of the model was near the optimum diagonal line, and decision curve analysis (DCA) showed a noticeably better benefit. Conclusion: CLNM in cN0 PTMC patients is associated with male sex, tumor size, extrathyroidal extension, HT, TERT promoter mutations and NRAS mutation. The prediction model exhibits good discrimination, calibration and clinical usefulness. This model will help to assess CLNM risk and make clinical decisions in cN0 PTMC patients. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of papillary thyroid microcarcinoma, defined as papillary thyroid carcinoma measuring 1cm or less in greatest diameter, has increased with improvements in ultrasound technology and widespread familiarity and utilization. Given the indolent course of papillary thyroid carcinoma, active surveillance is considered an acceptable alternative to surgical resection for select patients. Candidacy for active surveillance is determined by a number of patient and tumor characteristics. Specifically, the location of the tumor within the thyroid gland plays one of the key roles in decision making. Here we evaluate characteristics of the primary tumor and distance to the thyroid capsule in association with locoregional metastases to help guide risk assessment. Methods: Retrospective chart review of all thyroid surgeries performed by two surgeons at one medical center from 2014-2021 to evaluate characteristics of papillary thyroid microcarcinoma on preoperative ultrasound that are associated with locoregional metastatic disease. Results: Our data show a sensitivity of 65% and specificity of 95% for identifying regional metastases in papillary thyroid microcarcinoma using preoperative ultrasound. We found no correlation between regional metastasis and size of tumor, distance to thyroid capsule or trachea, tumor contour, or presence of autoimmune thyroiditis. Nodules in the superior or midpole were associated with central or lateral neck metastases, whereas nodules in the isthmus or inferior pole were only associated with central neck metastases. Conclusions: Active surveillance may be a reasonable option for even those papillary thyroid microcarcinomas adjacent to the thyroid capsule. [ABSTRACT FROM AUTHOR]

Thermal ablation (TA) has harvested favorable outcomes in treating low-risk papillary thyroid microcarcinoma (PTMC). Preoperative assessment, intraoperative procedures and postoperative follow-up are all closely linked with the success and safety of TA on PTMC. However, many details in these aspects have not been systematically reviewed. This review firstly described the influence of preoperative assessment, especially for the risk of lymph node metastasis (LNM), as well as the molecular testing on the selection of TA for PTMC. Besides, we also summarized the experiences in treating special PTMC cases by TA, like multifocal lesions, PTMC located in the isthmus or adjacent to the dorsal capsule. At last, we discussed the follow-up strategies, the influence of the thyroid-stimulating hormone (TSH) level on the prognosis of PTMCs, and the management for recurrent cases. In conclusion, the procedures during the entire perioperative period should be standardized to improve the outcomes of TA in treating PTMC patients. [ABSTRACT FROM AUTHOR]

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Objective: The purpose of this study was to predict the invasiveness of papillary thyroid microcarcinoma (PTMC) via ultrasonography in combination with the Wnt family member 10A (WNT10A) gene to provide a reference basis for evaluating the invasive capability of PTMC. Methods: Cancer tissue were collected from 182 patients with unifocal PTMC, and the patients were divided into the invasive group and the non-invasive group based on whether the lesions invaded the thyroid capsules or whether lymph node metastasis occurred. The expression of WNT10A protein was examined. Age, sex, maximum nodule diameter, color Doppler flow imaging (CDFI), nodule echo, microcalcification, aspect ratio, morphology (boundary), nodule location, internal structure, ultrasound-suspected lymph node metastasis (US-LNM), and WNT10A expression were compared between the invasive group and the non-invasive group. Univariate analysis and multivariate logistic regression analysis were performed, and a p value of less than 0.05 indicated that the difference was statistically significant. Results: (1) 36 patients in the non-invasive group showed high expression and 66 patients showed low or no expression, while 54 patients in the invasive group showed high expression and 26 patients showed low or no expression, suggesting that the expression level of WNT10A was higher in the invasive group than in the non-invasive group, with a statistically significant difference between the two groups (P<0.01). (2) Univariate analysis showed that there were statistically significant differences between the invasive PTMC group and the non-invasive group in age, sex, maximum nodule diameter, microcalcification, US-LNM and high WNT10A expression. (3) Multivariate analysis showed that the risk factors for invasiveness in patients with PTMC included age < 45 years, maximum nodule diameter > 7 mm, microcalcification, US-LNM and high WNT10A expression. Conclusion: The risk factors for PTMC invasiveness included age < 45 years, maximumnodule diameter >7 mm, microcalcification, US-LNM and high WNT10A expression. A combination of ultrasonography and WNT10A gene analysis could provide a reference basis for evaluating the invasive capability of PTMC. [ABSTRACT FROM AUTHOR]

Purpose: Familial papillary thyroid microcarcinoma (FPTMC) can present a more aggressive behavior than the sporadic microcarcinoma. However, few studies have analyzed this situation. The objective is to analyze the recurrence rate of FPTMC and the prognostic factors which determine that recurrence in Spain. Methods: Spanish multicenter longitudinal analytical observational study was conducted. Patients with FPTMC received treatment with curative intent and presented cure criteria 6 months after treatment. Recurrence rate and disease-free survival (DFS) were analyzed. Two groups were analyzed: group A (no tumor recurrence) vs. group B (tumor recurrence). Results: Ninety-four patients were analyzed. During a mean follow-up of 73.3 ± 59.3 months, 13 recurrences of FPTMC (13.83%) were detected and mean DFS was 207.9 ± 11.5 months. There were multifocality in 56%, bilateral thyroid involvement in 30%, and vascular invasion in 7.5%; that is to say, they are tumors with histological factors of poor prognosis in a high percentage of cases. The main risk factors for recurrence obtained in the multivariate analysis were the tumor size (OR: 2.574, 95% CI 1.210–5.473; p = 0.014) and the assessment of the risk of recurrence of the American Thyroid Association (ATA), both intermediate risk versus low risk (OR: 125, 95% CI 10.638–1000; p < 0.001) and high risk versus low risk (OR: 45.454, 95% CI 5.405–333.333; p < 0.001). Conclusion: FPTMC has a recurrence rate higher than sporadic cases. Poor prognosis is mainly associated with the tumor size and the risk of recurrence of the ATA. [ABSTRACT FROM AUTHOR]

Context Despite the wide revision of current guidelines, the management of papillary thyroid microcarcinoma (mPTC) still has to be decided case by case. There is conflicting evidence about the role of more frequent histological subtypes, and no data about potential differences at presentation. Objective Our aim was to compare the phenotype of the 2 most frequent mPTC variants, namely, classical papillary thyroid microcarcinoma (mPTCc) and the follicular variant of papillary thyroid microcarcinoma (mFVPTC). Methods Retrospective observational study, from January 2008 to December 2017 of a consecutive series of patients with mPTCc and mFVPTC. All cases were classified according to the 2015 American Thyroid Association (ATA) risk classification. Clinical and preclinical features of mPTCc and mFVPTC at diagnosis were collected. The comparison was also performed according to the incidental/nonincidental diagnosis and differences were verified by binary logistic analysis. Results In total, 235 patients were eligible for the analysis (125 and 110 mPTCc and mFVPTC, respectively). Compared with mPTCc, mFVPTCs were more often incidental and significantly smaller (4 vs 7 mm) (P <.001 all), possibly influenced by the higher rate of incidental detection. mFVPTC and incidental (P <.001 both) tumors were significantly more often allocated within the low - risk class. A logistic regression model, with ATA risk class as the dependent variable, showed that both mFVPTC (OR 0.465 [0.235-0.922]; P =.028]) and incidental diagnosis (OR 0.074 [0.036-0.163]; P <.001) independently predicted ATA risk stratification. Conclusion mFVPTC shows some differences in diagnostic presentation compared with mPTCc, and seems to retain a significant number of favorable features, including a prevalent onset as incidental diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Extrathyroidal extension (ETE) is considered a major prognostic factor in papillary thyroid carcinoma (PTC). Patients with gross ETE are at increased risk of recurrence and mortality. The importance of minimal ETE still remains controversial, especially in patients with papillary thyroid microcarcinoma (PTMC). The purpose of this study was to evaluate the association between ETE and lymph node (LN) metastasis in single PTMC. Methods A retrospective analysis was performed of 1994 patients underwent thyroidectomy for PTC between 2012 and 2016 in a single institution. Patients with combined thyroid carcinoma of other types and those who underwent completion thyroidectomy were excluded. After further exclusion of PTC larger than 1 cm and multifocal tumors, 814 patients with single PTMC were included in the study. Results 72.9% patients had no ETE, 25.1% minimal ETE, and 2.1% gross ETE. ETE was associated with lymphatic invasion, perineural invasion, and vascular invasion. Patients with minimal and gross ETE were also more likely to have LN metastasis, including lateral neck metastasis, compared to those without ETE. In univariate analysis, LN metastasis was associated with male gender, conventional PTC, lymphatic invasion, perineural invasion, and ETE. In multivariate analysis, male gender (OR = 1.987; 95% CI 1.369–2.884), lymphatic invasion (OR = 4.389; 95% CI 1.522–12.658), perineural invasion (OR = 6.545; 95% CI 1.262–33.948), and minimal ETE (OR = 1.852; 95% CI 1.298–2.643) were found to be independent risk factors of LN metastasis. Conclusions Minimal ETE is associated with LN metastasis in single PTMC, compared to no ETE. Minimal ETE should be considered in the management of patients with single PTMC, whether surgical or during active surveillance.

Abstract Background Part of papillary thyroid microcarcinoma (PTMC) has a high risk of tumor invasion and metastasis, which may occur in the regional lymph node metastasis or distant metastasis, severely threatening the life of patients. Invasion and metastasis are tightly involved in the proliferation, migration and invasion in cancer. This study aimed to investigate the role of tescalcin (TESC) in the proliferation, migration and invasion of PTMC. Methods The expressions of TESC in PTMC tissues and cells were detected by immunohistochemistry or qRT-PCR. Then, TPC-1 and BHT101 cells transfected with TESC-RNAi were used for the transcriptome sequencing. The proliferation, apoptosis, migration and invasion of TPC-1 and BHT101 cells were detected by CCK-8, colony formation, flow cytometric assay, transwell migration and scratch test. Moreover, TESC-RNAi transfected TPC-1 and BHT101 cells were subcutaneously injected into mice. Tumor volume and weight were calculated, and the positive rate of Ki-67 was determined by immunohistochemistry. Finally, the levels of c-Fos, ERK1/2 and p-ERK1/2 were determined by western blot. Results The expressions of TESC in PTMC tissues and cell lines were prominently enhanced. Transcriptome sequencing results showed that c-Fos was decreased in TPC-1 and BHT101 cells transfected with TESC-RNAi, which was associated with multiple different signaling pathways including the MAPK signaling pathway. Furthermore, TESC promoted the progress of PTMC by regulating the expression of c-Fos, which might be associated with the ERK signaling pathway. Conclusions TESC promoted the growth and metastasis of PTMC through regulating c-Fos/ERK1/2.

Abstract Background The presence of central lymph node metastases (CLNM) has been suggested as a risk factor for poorer prognosis and recurrence in papillary thyroid microcarcinoma (PTMC). However, the clinicopathologic factors for CLNM in clinical node-negative (CN0) PTMC were not well defined. This study aimed to perform a systematic review and meta-analysis to investigate the significant clinicopathologic predictors of CLNM in CN0 PTMC. Methods A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Web of Science. Case-control studies on the association of clinicopathologic risk factors with CLNM in CN0 PTMC were included. Results Thirteen eligible studies involving 6068 patients with CN0 PTMC were included. From the pooled analyses, male (odds ratio [OR]: 2.07, 95% CI: 1.49–2.87, P < 0.001), multifocality (OR: 1.88, 95% CI: 1.54–2.29, P < 0.001), tumor size > 5 mm (OR: 1.84, 95% CI: 1.55–2.18, P < 0.001), and extrathyroidal extension (OR: 1.96, 95% CI: 1.30–2.95, P = 0.001) are significantly associated with increased risk of CLNM in CN0 PTMC. A sample size with a cutoff point of 200 was identified as the source of heterogeneity for sex according to meta-regression (t = 3.18, P = 0.033). Then, the subgroup analysis of male was performed, which illustrated that male increased the risk of CLNM in the small sample group (SG) and the large sample group (LG) by 6.11-folds and 2.01-folds, respectively (SG: OR, 6.11, 95% CI, 3.16–11.81, P < 0.001; LG: OR, 2.01, 95% CI, 1.65–2.46, P < 0.001). Conclusions Male, multifocality, tumor size > 5 mm, and extrathyroidal extension may be reliable clinical predictors of CLNM in CN0 PTMC. Moreover, prophylactic central lymph node dissection should be considered in surgical decision-making for CN0 PTMC patients, who are male, multifocal, with tumor size > 5 mm, and with extrathyroidal extension. Trial registration CRD42021242211 (PROSPERO)

Abstract Background The present study aimed to quantify and differentiate the echo levels of papillary thyroid microcarcinomas (PTMCs) and micronodular goiters (MNGs) using the ultrasound grayscale ratio (UGSR) and to investigate the repeatability of UGSR. Methods The ultrasound (US) data of 241 patients with 265 PTMCs and 141 patients with 168 MNGs confirmed by surgery and pathology were retrospectively analyzed. All patients had received outpatient ultrasonic examination and preoperative ultrasonic positioning. The RADinfo radiograph reading system was used to measure the grayscales of PTMC, MNG, and thyroid tissues at the same gain level, and the UGSR values of the PTMC, MNG, and thyroid tissue were calculated. The patients were divided into outpatient examination, preoperative positioning, and mean value groups, and the receiver operating characteristic (ROC) curves were calculated to obtain the optimal UGSR threshold to distinguish PTMC from MNG. The interclass correlation coefficient (ICC) was used to assess the consistency of UGSR measured in three groups. Results The UGSR values of the PTMC and MNG were 0.56 ± 0.14 and 0.80 ± 0.19 (t = 5.84, P

The prevalence of thyroid carcinoma is increasing, and papillary thyroid carcinoma (PTC) is the most frequent subtype. More and more attention is being concentrated on the association between inflammation indicators and malignant tumors. The aim of the present study was to analyze whether the preoperative red blood cell distribution width (RDW) and platelet parameters, including mean platelet volume (MPV) and platelet distribution width (PDW), can be applied to distinguish between patients with PTC or papillary thyroid microcarcinoma (PTMC) and healthy controls, and to explore the associations with clinicopathological characteristics. The study retrospectively compared the RDW, MPV and PDW values of 780 patients with PTC or PTMC against a healthy control group. Receiver operating characteristic (ROC) curves were conducted to determine diagnostic accuracy. Furthermore, the clinicopathological features of the patients with PTC or PTMC were compared between higher and lower platelet parameter groups based on the RDW, MPV and PDW values. Significantly higher preoperative RDW, MPV and PDW values were found in patients with PTC or PTMC compared with those of the healthy group. ROC curve analysis showed that the area under the curve (AUC) plus 95% confidence interval (95% CI) values of RDW, MPV and PDW were 0.808 (0.780–0.835), 0.771 (0.743–0.799) and 0.711 (0.681–0.742), respectively. When RDW and MPV were combined together, the AUC (95% CI) value was enhanced to 0.858 (0.835–0.881) for the patients with PTC. For the patients with PTMC, RDW, MPV and PDW had AUC (95% CI) values of 0.812 (0.783–0.840), 0.779 (0.749–0.808) and 0.718 (0.685–0.751), respectively. When RDW and MPV were combined together, the AUC (95% CI) value was enhanced to 0.858 (0.835–0.881). A higher RDW was significantly associated with being female, deeper tumor infiltration, and normal FT3 and FT4 levels. A higher PDW was significantly associated with elevated thyrotropin receptor antibody levels. In conclusion, as convenient and available inflammation indicators, RDW, PDW and MPV have diagnostic ability and can distinguish between patients with PTC or PTMC and healthy controls. In addition, the combined application of RDW and MPV can improve the diagnostic power. The values of RDW and MPV were associated with clinicopathological characteristics. To the best of our knowledge, this is the first study to prove the usefulness of preoperative RDW combined with MPV in diagnosing patients with PTC or PTMC. [ABSTRACT FROM AUTHOR]

Confidence in long-term treatment results of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) is required in comparison with surgery and active surveillance (AS). The objective of this meta-analysis is to report more than three years of follow-up results of radiofrequency ablation for PTMCs. Ovid PUBMED, COCHRANE, and EMBASE databases were searched through Nov 19, 2023, for studies reporting outcomes in patients with PTMC treated with radiofrequency ablation and followed up for more than 3 years. The standard mean difference of the tumor volume before and after therapy, tumor recurrence, lymph node (LN) metastasis, distant metastasis, complications, and the pooled volume reduction rates (VRRs) at 1, 3, 6, 12, 24, 36, and 48 months after radiofrequency ablation were assessed. Data were extracted and methodological quality was assessed independently by two radiologists according to the PRISMA guidelines. Eight studies, involving 2131 patients, met the inclusion criteria through database searches. The overall VRR was 99.81 % (95 % CI: 99.68, 99.95) in the last follow-up. During a mean pooled follow-up of 46.59 months, 69 patients experienced local PTMC recurrence, with 8 cases within the ablation area. Additionally, 44 patients were diagnosed with newly discovered PTMC, and 17 patients exhibited lymph node metastases. Among the patients with PTMC recurrence, 3 were under active surveillance while 59 underwent additional RFA. The pooled mean complication rate was 2.80 %, with no instances of life-threatening or delayed complications. Radiofrequency ablation proves to be an effective local tumor control method for low-risk PTMC patients, resulting in clinically significant and enduring volume reduction. The rate of regrowth and retreatment requirement post-RFA was notably lower, positioning RFA as a compelling alternative to existing treatment options. [ABSTRACT FROM AUTHOR]

Introduction: The treatment of papillary thyroid microcarcinoma remains controversial. Central lymph node metastasis is common in papillary thyroid microcarcinoma and it is an important consideration in treatment strategy selection. Objective: The aim of this study was to investigate clinicopathologic risk factors and thyroid nodule sonographic characteristics for central lymph node metastasis in papillary thyroid microcarcinoma. Methods: We retrospectively reviewed the data of 599 papillary thyroid microcarcinoma patients who underwent surgery from 2005 to 2017 at a single institution. Univariate and multivariate analyses were used to identify the clinicopathologic factors and preoperative sonographic features of central lymph node metastasis. A receiver-operating characteristic, ROC curve analysis, was performed to identify the efficacy of ultrasonographic features in predicting central lymph node metastasis. A nomogram based on the risk factors was established to predict central lymph node metastasis. Results: The incidence of central lymph node metastasis was 22.4%. The univariate and multivariate analyses suggested that gender, age, multifocality, extrathyroidal invasion, and lateral lymph node metastasis were independent risk factors for central lymph node metastasis. The univariate and multivariate analyses revealed that nodular shape, margin, and calcification were independently associated with central lymph node metastasis. The ROC curve analysis revealed that the combination of shape, margin and calcification had excellent accuracy in predicting central lymph node metastasis. The nomogram was developed based on the identified risk factors for predicting central lymph node metastasis, and the calibration plot analysis indicated the good performance and clinical utility of the nomogram. Conclusions: Central lymph node metastasis is associated with male gender, younger age (

BackgroundDiagnosis of papillary thyroid microcarcinoma, defined as papillary thyroid carcinoma measuring 1cm or less in greatest diameter, has increased with improvements in ultrasound technology and widespread familiarity and utilization. Given the indolent course of papillary thyroid carcinoma, active surveillance is considered an acceptable alternative to surgical resection for select patients. Candidacy for active surveillance is determined by a number of patient and tumor characteristics. Specifically, the location of the tumor within the thyroid gland plays one of the key roles in decision making. Here we evaluate characteristics of the primary tumor and distance to the thyroid capsule in association with locoregional metastases to help guide risk assessment.MethodsRetrospective chart review of all thyroid surgeries performed by two surgeons at one medical center from 2014-2021 to evaluate characteristics of papillary thyroid microcarcinoma on preoperative ultrasound that are associated with locoregional metastatic disease.ResultsOur data show a sensitivity of 65% and specificity of 95% for identifying regional metastases in papillary thyroid microcarcinoma using preoperative ultrasound. We found no correlation between regional metastasis and size of tumor, distance to thyroid capsule or trachea, tumor contour, or presence of autoimmune thyroiditis. Nodules in the superior or midpole were associated with central or lateral neck metastases, whereas nodules in the isthmus or inferior pole were only associated with central neck metastases.ConclusionsActive surveillance may be a reasonable option for even those papillary thyroid microcarcinomas adjacent to the thyroid capsule.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Papillary thyroid microcarcinoma (PTMC) is defined as PTC with a diameter less than 1 centimeter. Most lymph nodes of PTC patients have metastasized to the central neck, and a few lymph nodes have metastasized to the lateral neck. Skip lymph node metastasis, that is, lateral cervical lymph node metastasis without central lymph node metastasis, is even less common. Additionally, distant metastasis of PTMC is also rare, mainly occurring in the lung and bone. Here, we reported a case of PTMC patient with skip lymph node metastasis and multiple distant metastasis. The patient presented with a huge shoulder mass and the primary tumor was found to originate from the thyroid. However, the patient only suffered with PTMC via postoperative pathological results, and interestingly, the patient only had skip lymph node metastasis. Thus, we should focus on PTMC patients with lateral cervical lymph nodes metastasis, especially those with skip metastasis. In addition, this case provides a new perspective for us to understand of skip lymph metastasis and distant metastasis of PTMC.

Wenfei Liu,* Shoufei Wang,* Xiaotian Xia Department of Thyroid, Parathyroid, Breast and Hernia Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaotian Xia Tel +86 18930172917Email 18930172917@163.comPurpose: Although the prognosis of papillary thyroid microcarcinoma (PTMC) is excellent, cervical lymph node metastasis (CLNM) is commonly observed in PTMC. This study aimed to investigate the incidence and risk factors for CLNM in PTMC.Patients and Methods: Altogether, 687 patients with PTMC who initially underwent unilateral thyroidectomy with unilateral central lymph node dissection or bilateral thyroidectomy with bilateral central lymph node dissection between January 2014 and June 2018 at our hospital were included. The patients were divided into two groups: PTMC with CLNM and PTMC with no CLNM. The clinicopathologic characteristics and ultrasound features were compared between the groups. Univariate and multivariate logistic regression analyses were used to identify the risk factors for CLNM.Results: CLNM was observed in 121/687 (17.6%) patients with PTMC. PTMC patients aged < 55 years exhibited a greater incidence of CLNM (87.6% vs 12.4%) than those aged ≥ 55 years. PTMC patients with CLNM were more likely to have capsular extension (24.0% vs 15.4%) and extension to the adjacent structures (9.9% vs 4.2%). Patients with microcalcification on ultrasound images were more likely to have CLNM (66.1% vs 47.9%). Multivariate logistic regression analysis revealed that microcalcification (odds ratio [OR]: 2.066, 95% confidence interval [CI]: 1.361– 3.135, P< 0.001), age < 55 years (OR: 2.341, 95% CI: 1.309– 4.187, P=0.004), capsular invasion (OR: 1.772, 95% CI: 1.082– 2.879, P=0.023), and invasion of the adjacent tissues (OR: 2.872, 95% CI: 1.355– 4.187, P=0.004) were significant risk factors for CLNM.Conclusion: Microcalcification, age < 55 years, capsular invasion, and invasion of the adjacent tissues were significant risk factors for CLNM in PTMC.Keywords: risk factors, papillary thyroid microcarcinoma, microcalcification, age, invasion

Active surveillance for low-risk papillary thyroid microcarcinoma (PTMC; T1aN0MI) was initiated at Kuma Hospital (Kobe, Japan) in 1993, based on a proposal by Akira Miyauchi. Favorable outcomes of such surveillance have been reported. Our latest study revealed 5- and 10-year tumor enlargement rates (by ≥ 3 mm) of 3.0% and 5.5% and 5- and 10-year node metastasis appearance rates of 0.9% and 1.1%, respectively. The postoperative prognosis did not differ between patients who underwent immediate surgery and those who underwent conversion surgery after progression. These findings suggest that active surveillance may be the best initial management of PTMCs. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) is the most frequent thyroid cancers worldwide. The efficacy and acceptability of radiofrequency ablation (RFA) in the treatment of PTC have been intensively studied. The aim of this study is to focus on extra detailed that may influent for PTC or papillary thyroid microcarcinoma (PTMC). Materials and methods: We identified a total of 1,987 records of a primary literature searched in PubMed, Embase, Cochrane Library, and Google Scholar by key words, from 2000 to 2022. The outcome of studies included complication, costs, and local tumor progression. After scrutiny screening and full-text assessment, six studies were included in the systematic review. Heterogeneity was estimated using I², and the quality of evidence was assessed for each outcome using the GRADE guidelines. Results: Our review enrolled 1,708 patients reported in six articles in the final analysis. There were 397 men and 1,311 women in the analysis. Two of these studies involved PTC and four focused on PTMC. There were 859 patients in the RFA group and 849 patients in the thyroidectomy group. By contrast, the tumor progression of RFA group was as same as that surgical groups [odds ratio, 1.31; 95% CI, 0.52-3.29; heterogeneity (I² statistic), 0%, p = 0.85]. The risk of complication rates was significantly lower in the RFA group than that in the surgical group [odds ratio, 0.18; 95% CI, 0.09-0.35; heterogeneity I² statistic), 40%, p = 0.14]. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the relationship between sonographic features and histological manifestations in the tall-cell variant of papillary thyroid microcarcinoma (TCV-PTMC), thus proposing the concept of "sonographic histology" and examine its value in the clinical management of the aggressive tall-cell variant. Methods: This study retrospectively included 104 participants who were admitted to Peking University Third Hospital from 2015 to 2022 and were histopathologically confirmed as having TCV-PTMC or classical PTMC. We mainly compared the general characteristics, sonographic characteristics, and pathological specimens between the two cohorts. Results: Hypoechoic nodules with a localized central isoechoic lesion and hypoechoic halo around nodules were most often observed in TCV-PTMC, which correlated with circumferentially distributed tumor epithelium and densely distributed tumor stroma histopathologically. Additionally, TCVPTMC showed nodules with a more regular margin and less microcalcification than classical PTMC, which led to an underestimation of the risk of TCV-PTMC. Conclusion: The good association between the ultrasound echo pattern and tissue cell arrangement was defined as sonographic histology in this study and can be applied in the preoperative identification of TCV-PTMC. This concept may provide novel insight for the identification of special subtypes of thyroid tumors and may modify pitfalls of the Thyroid Imaging Reporting and Data System in aggressive variants of microcarcinoma. [ABSTRACT FROM AUTHOR]

Background: Lateral lymph node metastasis (LLNM) is a risk factor of poor prognosis in papillary thyroid cancer (PTC). We aimed to determine predictive factors and develop the nomograms for LLNM in patients with papillary thyroid microcarcinoma (PTMC) and macro-PTC. Methods: We reviewed the medical records of 1,106 patients who underwent surgery between January 2019 and January 2022. Patients were divided into a PTMC and a macro-PTC group. We developed preoperative and postoperative nomograms for predicting LLNM based on results of multivariate analysis. Internal calibration was performed for these models. Results: The number of metastatic lymph nodes in lateral compartment was higher in macro-PTC patients. LLNM was independently associated with gender, the number of foci, location, shape, and central lymph node metastasis (CLNM) in PTMC patients. For macro-PTC patients, chronic lymphocytic thyroiditis, the number of foci, location, margin, CLNM, and central lymph node ratio were all independent predictors for LLNM. All the above factors were incorporated into nomograms, which showed the perfect discriminative ability. Conclusion: The diameter of the tumor has an impact on the rate of LLNM. Separate predictive systems should be used for PTMC and macro-PTC patients for more accurate clinical assessment of lateral lymph node status. Through these nomograms, we can not only detect high-risk patients with occult LLNM preoperatively, but also form appropriate treatment protocols for postoperative management of PTC patients with different risks. [ABSTRACT FROM AUTHOR]

Purpose: Papillary thyroid microcarcinoma (PTMC) is typically indolent in nature, allowing management with active surveillance protocols. Occasionally, a more aggressive phenotype can present and may lead to poor outcomes such as patients presenting with clinically significant lateral lymphadenopathy (cN1b). Prior analysis of the outcomes of this cohort is largely from papillary thyroid cancer (PTC) (>1 cm) or from institutions where use of radioactive iodine (RAI) is limited. Hence, we aim to describe the outcomes of patients with PTMC who presented with palpable cN1b disease, treated with total thyroidectomy and RAI. Methodology: We performed a retrospective cohort study. Outcomes of patients with PTMC who presented with palpable lateral lymph node (LN) metastases (microPTC cN1b) treated between 1997 and 2020 at Royal North Shore Hospital were compared with two control groups' outcomes: patients with clinically detected PTMC without evidence of involved LNs (microPTC cN0) and with larger PTC (>10 mm) who presented with palpable lateral lymphadenopathy (larger PTC cN1b). We assessed clinicopathological variables, postoperative risk stratification, rates of disease recurrence, reoperative surgery, and structural disease-free survival (DFS). Results: In total, 1534 PTMCs were diagnosed following thyroid surgery in the study period; of these, 157 (10%) were clinically detected microPTC cN0 and 26 microPTC cN1b (1.7%). There were 138 patients in the larger PTC cN1b control group. All cN1b patients were treated with total thyroidectomy and adjuvant RAI. Mean size of the largest LN deposit was similar between the microPTC cN1b and larger PTC cN1b groups (23 vs. 27 mm, p = 0.11). Patients with microPTC cN1b were more likely to have biochemical or structural persistence or recurrence compared with microPTC cN0 (19%, 5/26 vs. 3.8%, 6/157, p = 0.002) but less likely than larger PTC cN1b patients (19%, 5/26 vs. 42%, 58/138, p = 0.04). All patients in the microPTC cN1b group who had an excellent response to initial therapy (85%, 22/26) were disease free at last follow-up. The rate of reoperation was similar for the microPTC cN1b and microPTC cN0 groups (4%, 1/26 vs. 2%, 3/157, p = 0.461) and significantly lower than the larger PTC cN1b group (4%, 1/26 vs. 26%, 36/138, p = 0.002). Five-year DFS estimates were significantly better for microPTC cN1b patients than for larger PTC cN1b patients (94% vs. 59%, p = 0.001). Conclusions: MicroPTC cN1b patients treated with thyroidectomy and adjuvant RAI have inferior clinical outcomes compared with microPTC cN0 patients but have better outcomes than their larger PTC cN1b counterparts with respect to disease persistence and recurrence. Response to initial therapy provides valuable prognostication in microPTC cN1b patients: if these patients had an excellent response to initial treatment, they achieved long-term DFS in this series. [ABSTRACT FROM AUTHOR]

Non-invasive biomarkers for the diagnosis and prognosis of papillary thyroid microcarcinoma (PTMC) are still urgently needed. We aimed to characterize the N-glycome of PTMC, and establish nomograms for the diagnosis of PTMC and the prediction of lymph node metastasis (LNM). N-glycome of PTMC (LNM vs. non-LNM, capsular invasion (CI) vs. non-CI (NCI)) and matched healthy controls (HC) were quantitatively analyzed based on mass spectrometry. N-glycan traits associated with PTMC/LNM were used to create binomial logistic regression models and were visualized as nomograms. We found serum N-glycome differed between PTMC and HC in high-mannose, complexity, fucosylation, and bisection, of which, four N-glycan traits (TM, CA1, CA4, and A2Fa) were significantly associated with PTMC. The nomogram based on four traits achieved good performance for the identification of PTMC. Two N-glycan traits (CA4 and A2F0S0G) showed strong associations with LNM. The nomogram based on two traits showed relatively good performance in predicting LNM. We also found differences between CI and NCI in several N-glycan traits, which were not the same as that associated with LNM. This study reported serum N-glycosylation signatures of PTMC for the first time. Nomograms constructed from aberrant glycans could be useful tools for PTMC diagnosis and stratification. [ABSTRACT FROM AUTHOR]

Objective: To quantitatively predict the probability of lateral lymph node metastasis (LLNM) for papillary thyroid carcinomas (PTC) patients with central lymph node metastasis (CLNM) in order to guide postoperative adjuvant treatment. Methods: Five hundred and three PTC patients with CLNM from three medical centers were retrospectively analyzed. Results: The LLNM rate for all patients was 23.9% (120 in 503), with 15.5% (45 in 291) and 35.4% (75 in 212) for patients with papillary thyroid microcarcinoma (PTMC) and large papillary thyroid carcinoma (LPTC), respectively. Patients with no fewer than five positive central lymph nodes (CLN) exhibited a higher risk of LLNM. For patients with fewer than five positive CLN, a maximum diameter of positive CLN > 0.5 cm and the presence of ipsilateral nodular goiter were identified as independent risk factors of LLNM for papillary thyroid microcarcinoma (PTMC) patients. The independent risk factors of LLNM for large papillary thyroid carcinoma (LPTC) patients included a tumor located in the upper portion of thyroid, maximum tumor diameter ≥ 2.0 cm, maximum diameter of positive CLN > 0.5 cm, and the presence of thyroid capsular invasion. Predictive nomograms were established based on these risk factors for PTMC and LPTC patients, respectively. The accuracy and validity of our newly built models were verified by C-index and calibration curves. PTMC and LPTC patients with fewer than five positive CLN were each stratified into three subgroups based on their nomogram risk scores, and a detailed risk stratification flow chart was established for a more accurate evaluation of LLNM risk in PTC patients. Conclusions: A detailed stratification flow chart for PTC patients with CLNM to quantitatively assess LLNM risk was established, which may aid in clinical decision-making for those patients. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to construct a diagnostic model by exploring the potential predictors of high-risk Papillary Thyroid Microcarcinoma (PTMC) and verifying its reliability., Methods: A retrospective analysis of PTMC patients who underwent surgical treatment from 2004 to 2015 in the SEER database (training set) and the clinical pathological ultrasound information of PTMC patients at the Sichuan Provincial People's Hospital from 2020 to 2022 (external validation set) was conducted. In the training set, univariate and multivariate logistic regression analyses were used to screen independent predictive factors for high-risk PTMC patients in pathology. A nomogram diagnostic model was further constructed. Additionally, ROC curves and calibration curves were drawn to evaluate the efficiency of the model. In the external validation set, the diagnostic model was indirectly evaluated based on preoperative ultrasound imaging features to explore the feasibility and reliability of diagnosing high-risk PTMC through preoperative ultrasound imaging features., Results: A total of 1628 patients were included in the training set, and 530 patients were included in the test set. The independent risk factors for pathological high-risk PTMC were sex, age, tumor maximum diameter, tumor invasive, and cervical lymph nodes ( P <0.05). The C-index of the nomogram constructed based on these five factors was 0.947, with an optimal sensitivity of 96.7% and a specificity of 86.0%. The calibration curve showed that the model had high consistency. The area under the curve (AUC) value of the ROC curve for high-risk PTMC predicted by the risk score based on ultrasound features was 0.824 [95% CI (0.789, 0.860)], which was highly consistent with the risk score based on pathological features (κ= 0.758, P <0.05)., Conclusion: Indirect evaluation of a high-risk PTMC diagnostic model based on preoperative ultrasound imaging features had high predictive efficiency and potential value for clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liang, Fan, Zhang, Xu, Song, Huang and Wang.)

Background: Both endoscopic thyroid lobectomy and conventional thyroid lobectomy are effective modalities for treating papillary thyroid microcarcinoma (PTMC). However, their respective psychological and sleep quality ramifications in patients remain largely unexplored., Materials and Methods: Patients diagnosed with PTMC who underwent thyroid lobectomy at our institution between July 15, 2021, and July 15, 2022, were prospectively recruited. Psychological distress and sleep quality were assessed at five intervals (hospital admission, hospital discharge, and 1, 3, and 6 months posttreatment) utilizing four validated scales. The PTMC patients who completed the questionnaires diligently were subsequently categorized into either the endoscopic thyroid lobectomy group (trial group) or the conventional thyroid lobectomy group (control group). A propensity score matching (PSM) cohort was then established to examine longitudinal and cross-sectional alterations in psychological parameters., Results: Out of 602 eligible PTMC patients, 560 individuals completed all the questionnaires diligently during the follow-up period (response rate: 93.02%). This cohort comprised 176 patients (31.43%) who underwent endoscopic thyroid lobectomy and 384 patients (68.57%) who underwent conventional thyroid lobectomy. Following PSM, a comprehensive set of 176 matched patient pairs was successfully established. Both groups of patients exhibited a decline in sleep quality throughout the 6-month postoperative follow-up period; however, patients in the control group experienced concomitant elevation in anxiety levels. The PSQI scores of patients in the control group were markedly higher than those in the trial group across all follow-up time points, whereas the HAMA, HADS, and HEI scale scores did not significantly differ between the two groups., Conclusions: In terms of sleep quality and psychological well-being, endoscopic thyroid lobectomy is superior to conventional thyroid lobectomy for PTMC patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study aims to investigate the factors that influence the absorption of the ablation zone in patients with papillary thyroid microcarcinoma (PTMC) following microwave ablation (MWA) and construct a nomogram for predicting the absorption of the ablation zone., Methods: Data from 150 patients with 187 PTMCs who received MWA between April 2020 and April 2023 were analyzed. PTMCs were randomly divided into training and validation sets in a 7:3 ratio. Univariable and multivariable analyses of Cox regression were utilized to identify the independent variables associated with the absorption of the ablation zone in PTMC post-MWA, and a nomogram was established. The discrimination and calibration performance of the nomogram was assessed using the time-dependent receiver operating characteristic curves and calibration curves., Results: At 12 months post-MWA, a 53% proportion of complete disappearance of the ablation zone was observed. Energy delivered per milliliter of volume measured in contrast-enhanced ultrasound (CEUS) mode immediately post-MWA (Edv) and the CEUS margin at 1-month post-WMA were identified as independently correlated with the ablation zone absorption post-MWA (P = 0.001, P < 0.001 respectively). A nomogram incorporating these two factors was constructed. The areas under the receiver operating characteristic curve were all above 0.78 in the training and validation sets., Conclusion: Edv and the CEUS margin at 1-month post-MWA were found to be significantly associated with complete absorption of the ablation zone in PTMC patients following MWA. The established nomogram can assist practitioners in formulating more appropriate ablation strategies and provide a clinical basis for explaining the recovery status to patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To compare the prognosis of papillary thyroid microcarcinoma of the isthmus（PTMCI） after different surgical methods, and to investigate the most appropriate surgical plan for it, so as to provide reference for the selection of clinical surgical plan. Methods: The clinical data of 106 PTMCI patients diagnosed with postoperative pathology after surgical treatment in Department of Otolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital from January 2016 to June 2023 were retrospectively analyzed. The patients were divided into 3 groups according to whether there were nodules in the lateral lobe of the thyroid gland, namely, isolated PTMCI group, PTMCI group with unilateral lobe nodules, and PTMCI group with bilateral lobe nodules. Combined with follow-up information, the differences of recurrence rate, survival rate and postoperative complications after different surgical methods were compared among all groups. The surgical procedures included isthmic thyroidectomy, isthmic + unilateral lobectomy, and total thyroidectomy. All patients underwent central lymph node dissection at the same time. Results: There were no significant difference in recurrence rate, survival rate and postoperative complications among all groups and between groups. Postoperative recurrence occurred in 2 patients, among which 1 patient was PTMCI with multiple focal tumors in unilateral lobe undergoing isthmus + unilateral lobectomy + ipsilateral central lymph node dissection. The recurrence was manifested as contralateral cervical lymph node metastasis. Another case of PTMCI with bilateral benign nodules underwent isthmus + unilateral lobe（larger nodule） resection + ipsilateral central lymph node dissection, and the recurrence was manifested as residual glandular recurrence. One patient developed permanent hoarseness after surgery. The postoperative pathology of 31 patients（29.2%） indicated multiple focal thyroid carcinoma. Postoperative pathology of 41 patients（38.7%） suggested lymph node metastasis in the central region of neck. The disease-specific survival rate was 100%. Conclusion: Isthmic thyroidectomy is recommended for isolated PTMCI. Isthmus of thyroid+ unilateral lobectomy is feasible for PTMCI with unilateral lobectomy. If multiple suspicious malignant nodules（≥3） occur in unilateral lobectomy, total thyroidectomy is recommended. Total thyroidectomy is feasible for PTMCI with bilateral nodules. All PTMCI patients should undergo prophylactic central cervical lymph node dissection at the same time., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)