Papillary Thyroid Microcarcinoma Patients Research Articles

The relationship between ablation range and ablation energy in papillary thyroid microcarcinoma: a comparison between microwave ablation and laser ablation

ObjectivesTo study the relationship between the ablation range and applied energy of laser ablation (LA) and microwave ablation (MWA) in papillary thyroid microcarcinoma (PTMC).MethodsA total of 201 PTMC patients were treated with LA (n = 102) or MWA (n = 99) with single-applicator fixed ablation. The ablation range was determined by contrast-enhanced ultrasound. The ratios of ablation volume, longitudinal diameter, and orthogonal diameter to ablation energy (RAV/E, RAL/E, RAO/E) were analyzed and compared between MWA and LA. The effects of PTMC characteristics and Hashimoto’s thyroiditis (HT) on ablation efficiency were evaluated by linear regression.ResultsThe RAV/E was 0.72 (0.65–0.84) mm3/J for MWA and 0.48 (0.39–0.54) mm3/J for LA. HT was significantly correlated with RAV/E of LA (coefficient = − 0.367, p < 0.0001). RAL/E did not differ significantly between MWA and LA (MWA 0.026 mm/J, LA 0.025 mm/J; p = 0.957). However, MWA had a greater RAO/E than LA (MWA 0.014 mm/J, LA 0.012 mm/J; p < 0.0001). The plateau values of MWA and LA on the ablation orthogonal diameter were 10.7 mm and 8.69 mm, respectively.ConclusionsMWA showed a higher RAV/E than LA. More intuitively, MWA had a better ablation performance than LA on the orthogonal axis rather than the longitudinal axis. Theoretically, MWA and LA could achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin. HT had a negative effect on LA but not on MWA.Clinical relevance statementThis study establishes strong connections between ablation energy and ablation range in papillary thyroid microcarcinoma (PTMC) in vivo, possibly contributing to the supplementation of the PTMC Ablation Consensus or Guidelines and providing a scientific basis for choosing clinical ablation parameters in PTMC.Key Points• Both microwave ablation (MWA) and laser ablation (LA) have excellent performance on the ablation longitudinal axis (easily exceeding 10 mm) for papillary thyroid microcarcinoma (PTMC).• MWA performed much better than LA on the ablation orthogonal axis.• MWA and LA are expected to achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin.

Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations.

Genetic profiling is important for assisting the management of papillary thyroid microcarcinoma (PTMC). Although whole-exome sequencing (WES) of surgically resected PTMC tissue has been performed and revealed potential prognostic biomarkers, its application in PTMC fine-needle aspiration (FNA) specimens has not been explored. This study aimed to evaluate the feasibility of WES using FNA specimens of PTMC. Five PTMC patients were enrolled with clinical characteristics gathered. Fine aspiration cytology needle (23 gauges) was used to collect FNA biopsy with ultrasound guidance. WES analysis of FNA specimens from five PTMC patients and matched blood samples was performed. The WES of FNA samples yielded an average sequencing depth of 281× and average coverage of 99.5%. We identified 534 somatic single-nucleotide variants and 13 indels in total, and per sample, we found a mean of 24 exonic mutations, which affected a total of 120 genes. In the PTMC FNA samples, the most frequently mutated genes were BRAF and ANKRD18B, and the four driver genes were BRAF, AFF3, SRCAP, and EGFR. We also identified several germline cancer predisposing gene mutations. The results suggest that WES of FNA specimens is feasible for PTMC and can identify novel genetic mutations.

Efficacy and safety of thermal ablation modalities for the treatment of papillary thyroid microcarcinoma: Systematic Review and network meta-analysis

BackgroundThermal ablation (TA) modalities such as radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) have been widely used in the treatment of papillary thyroid microcarcinoma (PTMC) patients. Based on previous small-sample meta-analyses, this network meta was designed to further compare the efficacy and safety of these thermal ablation methods in PTMC patients. MethodsChina National Knowledge Infrastructure (CNKI), Wanfang, PubMed, Embase, and the Cochrane Library databases were searched to retrieve relevant studies published before May 2022. The efficacy outcomes was recurrence and lymph node metastasis (LNM), the safety outcome included operation time, intra-operative blood loss, hospital stays and complications. The Newcastle-Ottawa Scale (NOS) was selected for the risk of bias assessment. Stata 14.0 was used for statistical analysis. ResultsTwenty-nine articles were included. Based on as least 6 months follow up, our analysis discovered no significant statistical differences in all efficacy and safety outcomes between MWA, RFA, and LA groups. Moreover, three TA treatments all produced significant least operation time, hospital stays, and complications than surgery group. Additionally, our study found that RFA showed relatively less complications, LNM, operation time and intra-operative blood loss, compared with other TA treatments. MWA indicated the lowest probability of recurrence, LA showed the longest hospital stays. ConclusionsMWA, RFA, and LA are all effective treatment strategies for patients with PTMC, but could not completely replace conventional surgical treatment.

Development and Validation of a Computed Tomography-Based Radiomics Nomogram for the Preoperative Prediction of Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma

This study aims to develop and validate a computed tomography (CT)-based radiomics nomogram for pre-operatively predicting central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC) and explore the underlying biological basis by using RNA sequencing data. This study trained 452 PTMC patients across two hospitals from January 2012 to December 2020. The sets were randomly divided into the training (n = 339), internal test (n = 86), external test (n = 27) sets. Radiomics features were extracted from primary lesion's pre-operative CT images for each patient. After screening for features, five algorithms such as K-nearest neighbor, logistics regression, linear-support vector machine (SVM), Gaussian SVM, and polynomial SVM were used to establish the radiomics models. The performance of these five algorithms was evaluated and compared directly to radiologist's interpretation (CT-reported lymph node status). The radiomics signature score (Rad-score) was generated using a linear combination of the selected features. By combining the clinical risk factors and Rad score, a radiomics nomogram was established and compared with Rad-score and clinical model. The performance of the nomogram was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve, and the decision curve analysis (DCA). The potential biological basis of nomogram was revealed by performing genetic analysis based on the RNA sequencing data. A total of 25 radiomic features were ultimately selected to train the machine learning models, and the five machine learning models outperformed the radiologists' interpretation by achieving area under the ROC curves (AUCs) ranging from 0.606 to 0.730 in the internal test set. By incorporating the Rad score and clinical risk factors (sex, age, tumor-diameter, and CT-reported lymph node status), this nomogram achieved AUCs of 0.800 and 0.803 in the internal and external test set, which were higher than that of the Rad-score and clinical model, respectively. Calibration curves and DCA also showed that the nomogram had good performance. As for the biological basis exploration, in patients predicted by nomogram to be PTC patients with CLMN, 109 genes were dysregulated, and some of them were associated with pathways and biological processes such as tumor angiogenesis. This radiomics nomogram successfully identified CLNM on pretreatment imaging across multiple institutions, exceeding the diagnostic ability of radiologists and had the potential to be integrated into clinical decision making as a non-invasive pre-operative tool.

Prediction of central lymph node metastasis in patients with papillary thyroid microcarcinoma by gradient-boosting decision tree model based on ultrasound radiomics and clinical features.

In recent years, the study of radiomics in thyroid diseases has developed rapidly. This study aimed to establish a preoperative radiomics prediction model for central compartment lymph node metastases (CLNMs) in papillary thyroid microcarcinoma (PTMC) patients using gradient-boosting decision tree (GBDT) model and evaluate the performance of the model. A total of 274 patients with PTMC admitted for thyroid surgery at China-Japan Union Hospital of Jilin University from January 2020 to July 2022 were retrospectively analyzed. Patients were randomized into training and validation cohorts according to a ratio of 8:2. Radiomics features were extracted from the ultrasound (US) images of PTMC lesions. The open-source software Pyradiomics was used to extract radiomics features, and WEKA software was used to select CLNM-related radiomics features. Clinical risk factors for CLNM were screened by statistical methods. The GBDT model was constructed by combining radiomics features and clinical risk factors, and compared with the diagnostic efficacy of US-reported cervical lymph node status. Shapley Additive exPlanations (SHAP) was applied to visualize and analyze the GBDT model globally and locally. A total of seven radiomics features were significantly correlated with central lymph node status in the training and validation cohorts. The predictors in the GBDT model included the radiomics features, sex, age, and body mass index (BMI). The area under the curve (AUC) values of the GBDT model in the training and validation cohorts were 0.946 [95% confidence interval (CI): 0.920-0.972] and 0.845 (95% CI: 0.714-0.976), respectively, compared with 0.583 (95% CI: 0.508-0.659) and 0.582 (95% CI: 0.430-0.736) for US-reported lymph node status alone. The Delong test showed a significant difference between AUS in the training and validation cohorts (P<0.001, respectively). SHAP visual analysis showed the effect of each parameter on the GBDT model globally and locally. Decision curve analysis demonstrated the clinical utility of the GBDT model. The prediction of CLNM by the GBDT model, based on US radiomics features and clinical factors, can be better than that by using US alone in patients with PTMC. Furthermore, the GBDT model may serve a guidance of clinical decision for patient's treatment strategy.

A nomogram based on ultrasound radiomics for predicting the invasiveness of cN0 single papillary thyroid microcarcinoma.

Up to 15.3% of papillary thyroid microcarcinoma (PTMC) patients with negative clinical lymph node metastasis (cN0) were confirmed to have pathological lymph node metastasis in level VI. Conventional ultrasound (US) focuses on the characteristics of tumor capsule and the periphery to determine whether the tumor has invasive growth. However, due to its small size, the typical features of invasiveness shown by conventional 2-dimensional (2D) US are not well visualized. US-based radiomics makes use of artificial intelligence and big data to build a model that can help improving diagnostic accuracy and providing prognostic implication of the disease. We hope to establish and assess the value of a nomogram based on US radiomics combined with independent risk factors in predicting the invasiveness of a single PTMC without clinical lymph node metastasis (cN0). A total of 317 patients with cN0 single PTMC who underwent US examination and operation were included in this retrospective cohort study. Patients were randomly divided into training and testing set in the ratio of 8:2. The US images of all patients were segmented, and the radiomics features were extracted. In the training dataset, the US with features of minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) were selected and radiomics signatures were then established according to their respective weighting coefficients. Univariate and multivariate logistic regression analyses were employed to generate the risk factors of possible invasive PTMC. The nomogram is then made by combining high risk factors and the radiomics signature. The efficiency of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and calibration curve, and its clinical application value was assessed by decision curve analysis (DCA). The testing dataset was used to validate the model. In the model, seven radiomics features were selected to establish the radiomics signature. A nomogram was made by incorporating clinically independent risk factors and the radiomics signature. Both the ROC curve and calibration curve showed good prediction efficiency. The area under the curve (AUC), accuracy, sensitivity, and specificity of the nomogram in the training data were 0.76 [95% confidence interval (CI): 0.71-0.82], 0.811, 0.914, and 0.727, respectively whereas the results of the testing dataset were 0.71 (95% CI: 0.58-0.84), 0.841, 0.533, and 0.868. As such, the efficacy of the nomogram in predicting the invasiveness of PTMC was subsequently validated by the DCA. Nomogram based on thyroid US radiomics has an excellent predictive value of the potential invasiveness of a single PTMC without clinical lymph node metastasis. With these promising results, it can potentially be the imaging marker used in daily clinical practice.

Clinical factors for choosing active surveillance: an analysis of papillary thyroid microcarcinoma patients with recurrence.

Active surveillance (AS) has been suggested as a management option for low-risk papillary thyroid microcarcinoma (PTMC). However, the currently proposed selection criteria for AS application do not consider various clinical factors. The purpose of this study was to analyze clinical factors related to recurrence that could be confirmed preoperatively in patients who underwent surgery for PTMC and to identify factors worth considering when deciding whether to apply AS. Data were collected from patients with PTMC who underwent surgical treatment at Chungnam National University Hospital. A retrospective cohort was established according to the presence or absence of recurrence during the follow-up period. In total, 2717 patients were enrolled, of whom 60 experienced recurrence. Various clinical factors that could be identified before surgery were analyzed. The relationship between various clinical factors that could be confirmed preoperatively and recurrence was confirmed through Cox regression analysis and Kaplan-Meier curve analysis. BRAF mutation and the tall cell variant were significantly more common in patients with recurrence. In patients aged 55 years or older, the risk of recurrence was lower than in younger patients, while the recurrence-free survival (RFS) rate was higher. When choosing between surgical treatment or AS in PTMC patients, additional consideration of the patient's clinical factors, such as age and BRAF mutation status, may be required in addition to the existing criteria.

Survival benefits of extensive surgery in patients with papillary thyroid microcarcinoma

BackgroundDespite the guidelines recommending thyroid lobectomy, many papillary thyroid microcarcinoma (PTMC) patients still undergo total thyroidectomy. PTMC's optimal treatment remains unclear. We aimed to determine whether total thyroidectomy improves outcomes compared to less extensive surgery. MethodsWe analyzed 6064 PTMC adult patients from the Surveillance, Epidemiology, and End Results (SEER) database (2000–2019) who underwent either total thyroidectomy (n ​= ​3652) or less extensive surgery (n ​= ​2412). Endpoints were overall survival, cancer-specific survival, and recurrence. ResultsTotal thyroidectomy patients had a 5.2 ​% mortality rate versus 8.1 ​% with less extensive surgery. Recurrence occurred in 1 (0.03 ​%) total thyroidectomy patient compared to 24 (1.0 ​%) less extensive surgery patients (HR 0.07, p ​= ​0.01). Median survival was 8.1 years for total thyroidectomy versus 8.8 years for less extensive surgery. Overall survival favored total thyroidectomy (p ​= ​0.001) but cancer-specific survival did not differ. ConclusionAlthough total thyroidectomy may not improve cancer-specific survival, it lowers recurrence risk and confers an overall survival advantage for PTMC patients. These findings may help guide surgical decisions.

ATA risk stratification in papillary thyroid microcarcinoma has low positive predictive value when identifying recurrence

BackgroundRising incidence of papillary thyroid microcarcinomas (PTMC) has raised concerns for overdiagnosis. Utility of the American Thyroid Association Risk Stratification System (ATA-RSS) 2015 in predicting risk of disease recurrence in patients with PTMC was assessed. MethodsElectronic health records of patients who underwent total thyroidectomy were queried. ATA-RSS 2015 risk stratification was performed on those with PTMC, and validity for predicting disease recurrence was calculated. ResultsWith 10-year median follow up, recurrence was higher in PTMC patients with high/intermediate vs low ATA risk (33 % vs 4 %, p = 0.002). Sensitivity of ATA-RSS for detecting recurrence was 60 %, specificity 90 %, PPV 33.3 %, NPV 96.6 %, and accuracy 88 %. When microscopic extrathyroidal extension (ETE) was excluded as an intermediate risk criterion, PPV improved to 50 % and accuracy improved to 92.5 % ConclusionsATA-RSS 2015 predicts recurrence in PTMC with high NPV but low PPV. Exclusion of microscopic ETE improved PPV, which may help prevent overtreatment.

In search of new stratification strategies: tissue proteomic profiling of papillary thyroid microcarcinoma in patients with localized disease and lateral neck metastases.

Papillary thyroid carcinomas (PTC) are the most common thyroid malignancies that are often diagnosed as microcarcinomas when the tumor is less than one centimetre in diameter. Currently, there are no valid stratification strategies that would reliably assess the risk of lateral neck metastases and optimize surgical treatment. Aiming to find potential tissue biomarkers of metastatic potential, we conducted a cross-sectional proteomic pilot study on formalin-fixed paraffin-embedded tissues of metastatic (N = 10) and non-metastatic (N = 10) papillary thyroid microcarcinoma patients. Samples were analysed individually using liquid chromatography/mass spectrometry, and the differentially expressed proteins (DEP) were functionally annotated. We identified five overexpressed DEPs in the metastatic group (EPB41L2, CSE1L, GLIPR2, FGA and FGG) with a known association to tumour biology. Using bioinformatic-based tools, we found markedly different profiles of significantly enriched biological processes between the two groups. The identified DEPs might have a role as potential tissue biomarkers for PTC metastases. However, further prospective research is needed to confirm our findings.

BRAF V600E mutation in papillary thyroid microcarcinoma: is it a predictor for the prognosis of patients with intermediate to high recurrence risk?

The BRAFV600E mutation is the universal genetic mutation in papillary thyroid microcarcinoma (PTMC). The present study is to estimate the role of the BRAFV600E mutation in the clinical outcome of PTMC with intermediate to high recurrence risk after radioactive iodine (RAI) therapy, which is considered to be an indolent tumor. We conducted a single-center retrospective study. Between May 2016 and March 2019, PTMC patients with known BRAFV600E status who received RAI therapy were reviewed at the Second Hospital of Shandong University. Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. The association between the BRAFV600E mutation and clinicopathological characteristics, response to RAI therapy, and recurrence after a period of follow-up were analyzed. Propensity score matching (PSM) and logistic regression were used to control confounding variables. Of the 322 patients with intermediate to high recurrence risk in PTMC, the mean age of the patients were 43.7 ± 12.2 years, and 72.1% were women. BRAFV600E mutation was found in 64.9% (209/322). After PSM, 112 pairs of patients were matched, and except for multifocality (P = 0.001), extrathyroidal invasion (P = 0.003) and tumor size (P = 0.03), there was no significant difference in all baseline characteristics between the two groups. An excellent response (ER) to RAI therapy was observed in 273 patients (84.7%). At the end of the study, 17(5.2%) and 6(1.8%) patients showed structural incomplete response (SIR) and biochemical incomplete response (BIR) status. The proportion of patients who achieved ER status in the BRAFV600E mutation positive and negative groups was 86.6% and 81.4%, respectively. Kaplan-Meier analyses showed that the BRAFV600E mutation was not related to lower ER reached time. The median follow-up was 51 months. We found the BRAFV600E mutation was associated with multifocality, extrathyroidal invasion, and tumor size in papillary thyroid microcarcinoma. However, the BRAFV600E mutation had no significant association with clinical outcomes in patients with intermediate to high recurrence risk after RAI therapy. Furthermore, the extra-thyroid uptake results and distant metastasis had been proven to be independent factor predicting the clinical response. ChiCTR2200062911.

The safety and efficacy of delayed surgery by simulating clinical progression of observable papillary thyroid microcarcinoma: a retrospective analysis of 524 patients from a single medical center.

When active surveillance (AS) is developed in the patients with low-risk papillary thyroid microcarcinoma (PTMC), a medical center needs to ensure the delayed operation that is caused by PTMC clinical progression to have the same prognosis as that of immediate operation. The objective of this study was to investigate the efficacy of delayed surgery by simulating clinical progression (tumor size enlargement and appearance of lymph node metastasis) of PTMCs with AS in a single medical center. We retrospectively analyzed the response to therapy in 317 papillary thyroid carcinoma patients treated with total thyroidectomy and post-operative radioactive iodine ablation. They were classified into three groups according to tumor size (group A ≤0.5 cm; group B >0.5cm and ≤1 cm; group C >1cm and ≤1.5 cm) or two groups according to the presence (cN1) or absence (cN0) of the clinical lymph node (LN) metastasis. Groups C and cN1 were regarded as simulated clinical progression of observational PTMC and the operation for them was assumed to be "delayed surgery". However, Groups A, B and cN0 were regarded as no clinical progression and the operation for them was considered as immediate surgery. There were no significantly differences in excellent response to therapy and recurrence-free survival not only among the group A, B and C, but also between the group cN0 and cN1. In other words, these insignificant differences were found between immediate and simulated "delayed" surgeries. For the PTMC patients suitable for AS, the oncological outcomes were also excellent even if surgery was delayed until after the presence of clinical progression, according to our clinical simulation. Furthermore, we consider that it was feasible for medical centers to assess the ability to implement AS for PTMC patients by retrospectively analyzing their own previous clinical data using the described simulation.

Incidence and risk factors for occult lesions in low-risk papillary thyroid microcarcinoma patients with tumor characteristics appropriate for thermal ablation: A retrospective study.

In recent years, thermal ablation has been increasingly employed for the treatment of low-risk papillary thyroid microcarcinoma (PTMC) across various institutions. Its use as a standard or initial treatment continues to be a subject of debate. Retrospective analyses of the surgical pathology in post-ablation patients have indicated that occult lesions are not uncommon. This retrospective study aimed to examine the incidence and risk factors of occult lesions via postoperative pathology in low-risk PTMC patients who fulfilled the criteria for thermal ablation therapy. We examined the medical records of patients who underwent thyroid surgery and had a Bethesda classification V or VI based on fine needle aspiration cytology between November 22, 2020, and December 31, 2022. A total of 413 patients with preoperative tumor characteristics appropriate for thermal ablation were included in this study. Occult lesions, encompassing ipsilateral or contralateral occult carcinoma or central lymph node metastases may have occurred in 34.7% of patients. Male gender (OR: 2.526, 95% CI: 1.521-4.195, P = .000), tumor location in the lower pole (OR: 1.969, 95% CI: 1.186-3.267, P = .009), multiple microcalcifications (OR: 5.620, 95% CI: 2.837-11.134, P = .000), and Hashimoto's thyroiditis (OR: 2.245, 95% CI: 1.292-3.899, P = .004) were independent risk factors for the presence of occult lesions. In low-risk PTMC patients exhibiting tumor characteristics amenable to thermal ablation, over one-third of the patients may present with occult lesions. Meticulous evaluation of the presence of additional lesions is necessary before performing thermal ablation, particularly in patients exhibiting high-risk factors for occult lesions.

A novel nomogram for identifying high-risk patients among active surveillance candidates with papillary thyroid microcarcinoma.

Active surveillance (AS) has been recommended as the first-line treatment strategy for low-risk (LR) papillary thyroid microcarcinoma (PTMC) according to the guidelines. However, preoperative imaging and fine-needle aspiration could not rule out a small group of patients with aggressive PTMC with large-volume lymph node micro-metastasis, extrathryoidal invasion to surrounding soft tissue, or high-grade malignancy from the AS candidates. Among 2,809 PTMC patients, 2,473 patients were enrolled in this study according to the inclusion criteria. Backward stepwise multivariate logistic regression analysis was used to filter clinical characteristics and ultrasound features to identify independent predictors of high-risk (HR) patients. A nomogram was developed and validated according to selected risk factors for the identification of an HR subgroup among "LR" PTMC patients before operation. For identifying independent risk factors, multivariable logistic regression analysis was performed using the backward stepwise method and revealed that male sex [3.91 (2.58-5.92)], older age [0.94 (0.92-0.96)], largest tumor diameter [26.7 (10.57-69.22)], bilaterality [1.44 (1.01-2.3)], and multifocality [1.14 (1.01-2.26)] were independent predictors of the HR group. Based on these independent risk factors, a nomogram model was developed for predicting the probability of HR. The C index was 0.806 (95% CI, 0.765-0.847), which indicated satisfactory accuracy of the nomogram in predicting the probability of HR. Taken together, we developed and validated a nomogram model to predict HR of PTMC, which could be useful for patient counseling and facilitating treatment-related decision-making.

Clinical relevance and outcome of familial papillary thyroid cancer: a single institution study of 626 familial cases.

Whether familial thyroid cancer is more aggressive than sporadic thyroid cancer remains controversial. Additionally, whether the number of affected family members affects the prognosis is unknown. This study focused mainly on the comparison of the clinicopathological characteristics and prognoses between papillary thyroid cancer (PTC) patients with and without family history. A total of 626 familial papillary thyroid cancer (FPTC) and 1252 sporadic papillary thyroid cancer (SPTC) patients were included in our study. The clinical information associated with FPTC and SPTC was recorded and analyzed by univariate analysis. Patients in the FPTC group had a higher rate of multifocality (p=0.001), bilaterality (p=0.000), extrathyroidal invasion (p=0.000), distant metastasis (p=0.012), lymph node metastasis (p=0.000), recurrence (p=0.000), a larger tumor size (p=0.000) and more malignant lymph nodes involved (central: p=0.000; lateral: p=0.000). In addition, our subgroup analysis showed no significant difference (p>0.05) between patients with only one affected family member and those with two of more group in all clinicopathological characteristics. In papillary thyroid microcarcinoma (PTMC) subgroup analysis, we found that FPTMC patients harbored significantly larger tumors (p=0.000), higher rates of multifocality (p=0.014), bilaterality (p=0.000), distant metastasis (p=0.038), lymph node metastasis (p=0.003), greater numbers of malignant lymph nodes (central: p=0.002; lateral: p=0.044), higher rates of I-131 treatment (p=0.000) and recurrence (p=0.000) than SPTMC patients. Our results indicated that PTC and PTMC patients with a positive family history had more aggressive clinicopathological behaviors, suggesting that more vigilant screening and management for FPTC may be helpful.

Association between iodine nutrition and cervical lymph node metastasis of papillary thyroid microcarcinoma.

We aimed to investigate the association between iodine intake and nodal metastasis stratified by central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) of papillary thyroid microcarcinoma (PTMC). Urinary iodine concentration (UIC) and clinicopathological characteristics were used to identify factors associated with CLNM and LLNM using logistic regression analysis. A sum of 3,858 PTMC patients were enrolled. The median UIC (MUI) of patients with CLNM or LLNM was not statistically different from those without nodal metastasis. Male patients had a higher MUI than females (183.4 μg/L vs. 173.6 μg/L). Female patients with extracapsular extension had a higher MUI than those without it (210.0 μg/L vs. 172.1 μg/L). Male patients with LLNM had a significantly lower MUI than those without LLNM (134.7 μg/L vs. 187.9 μg/L). Female patients with more than adequate iodine intake were more likely to present with CLNM and extrathyroidal extension than those with adequate iodine intake with an odds ratio (95% confidence interval) of 1.23 (1.01-1.51) and 1.59 (1.09-2.32) after adjustment. Iodine nutrition was not found to be associated with LLNM. In addition, patients with a younger age, larger tumors, extrathyroidal extension, and intrathyroidal spread were more likely to be CLNM, whereas nodular goiter presented with a protective factor; CLNM was the only factor associated with LLNM of PTMC in both genders. In conclusion, iodine nutrition has a much closer association with female than male patients, and high iodine intake may be associated with CLNM and extrathyroidal extension in female PTMC patients.

The role of multifocality in predicting central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma.

To determine the predictive ability of multifocality for central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma. Retrospective review. Tertiary medical center. We retrospectively collected clinical data from initially treated papillary thyroid microcarcinoma (PTMC) patients at Cancer Hospital Chinese Academy of Medical and sciences between January 1st, 2018, and December 31st, 2018. Data from 975 initially treated 18-55 years old female patients with unilateral PTMC was collected. We also collected data from 340 initially treated 18-55 years old male patients with unilateral PTMC patients to compare the results between genders. Clinicopathological factors associated with central lymph node metastasis (CLNM) were investigated by univariate and multivariate analysis. (1) In the female group, there were 196 (20.1%) cases that had tumor multifocality, including 126 (12.9%) with 2 foci and 70 (7.2%) with >2 foci. The risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus (37.3% vs 38.6%, P=0.775). However, diagnosed with >2 foci were independently and positively correlated with CLNM (OR=2.708, 95%CI=1.592-4.607, P<0.001), as was tumor diameter >0.55cm (OR=2.047, 95%CI=1.535-2.730, P<0.001). (2) In the male group, the risk of CLNM with 2 foci was significantly higher than 1 focus (P=0.008). Compared to female patients, the risk of CLNM was significantly higher in patients with 1 focus (P<0.001) or 2 foci (P<0.001). In summary, the risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus, while multifocality with over 2 foci was an independent risk factor of CLNM. Therefore, multifocality in this subgroup should not be simply defined as "more than 1 focus". Future models that include multifocality as a predictive factor for cervical lymph node metastasis could consider stratifying the cohort into smaller subgroups for more accurate conclusions.

Hashimoto's thyroiditis is negatively associated with lymph node metastasis in PTMC.

The association between Hashimoto's thyroiditis (HT) and lymph node metastasis (LNM) of papillary thyroid microcarcinoma (PTMC) remains poorly understood. We aimed to elucidate the impact of HT on PTMC and its association with LNM. A retrospective cohort study was conducted at a single cancer referral center. Patients diagnosed with PTMC and complete clinicopathological results between January 2013 and June 2018 were included. Propensity score matching (PSM) and logistic regression analysis were performed to evaluate the difference in LNM characteristics between patients with and without HT. Among the 9929 PTMC patients, 2389 (24.1%) were pathologically diagnosed with HT. After PSM using variables including age, sex, primary tumor size, central neck dissection, extrathyroidal extension (ETE), gross ETE, multifocality and bilaterality, we identified 2324 pairs of patients for analysis. Patients with HT had a significantly lower incidence of LNM in the central neck (40.9% vs 56.2%, P < 0.001) and lateral neck (11.6% vs 14.2%, P = 0.016), a lower incidence of extranodal extension (ENE) (10.1% vs 17.0%, P < 0.001), fewer positive lymph nodes (median [IQR], 0 [0 to 2] vs 1 [0 to 3], P < 0.001), and a lower lymph node ratio (median [IQR], 0.00 [0.00 to 0.15] vs 0.12 [0.00 to 0.33], P < 0.001) than those without HT. Logistic regression analysis indicated that patients with HT had a significantly reduced risk of CLNM and LLNM compared to those without HT. Our study indicated a negative association between HT and LNM in PTMC.

Lateral lymph node metastasis in papillary thyroid microcarcinoma: a study of 5241 follow-up patients.

To investigate the impact of lateral lymph node metastasis in papillary thyroid microcarcinoma (PTMC). 5241 PTMC patients with follow-up information were enrolled in the current study. These patients underwent primary surgery in our situation from January 1997 to December 2016. Additionally, a validation cohort consisting of 274 PTMC patients who underwent primary surgery between January 2020 and December 2021 was also included. Univariable and multivariate logistic analyses were conducted to identify the association between clinicopathologic features and lateral lymph node metastasis (LLNM). Kaplan-Meier survival curve analysis was used to calculate the disease-free survival (DFS) rate. The fitting curve was generated to identify the quantitative relationship between central lymph node metastases (CLNM) and LLNM. Of 5241 PTMC patients, cervical lymph node metastasis was detected in 1494 (28.5%) cases, including 1364 (26.0%) with CLNM only and 130 (2.5%) with LLNM. With a median follow-up time of 60 months (interquartile range [IQR], 44-81), recurrence was detected in 114 patients (2.2%). Multivariate Cox regression analyses showed that LNM was the only independent risk factor for recurrence, with HR values of 3.03 in CLNM and 11.14 in LLNM, respectively. Tumor diameter >0.5 cm (hazard ratio [HR]:1.80), multifocality (HR:2.59), bilaterality (HR:2.13), extrathyroidal invasion (HR:2.13), and CLNM (HR:5.11) were independent risk factors for LLNM. The prevalence of LLNM escalated significantly with increasing number of lymph node involvement in CLNM when stratified by the number of metastatic lymph nodes and trend was observed similarly in the validation cohort. The fitting curve showed that the incidence of LLNM could be as high as 20.7% when the number of CLNM ≥ 5. By analyzing a large database with follow-up information, our study provides evidence that LLNM is significantly correlated with tumor recurrence in patients with PTMC. Tumor size (>0.5 cm), multifocality, bilaterality, extrathyroidal extension (ETE) and CLNM are independent risk factors for LLNM.

Long-term efficacy of microwave ablation for multifocal papillary thyroid microcarcinoma: a 5-year follow-up study.

Microwave ablation (MWA) has achieved excellent long-term efficacy in treating unifocal papillary thyroid microcarcinoma (UPTMC). The therapeutic effect of this treatment on multifocal papillary thyroid microcarcinoma (MPTMC) is unknown. Therefore, we evaluated the long-term efficacy of MWA for low-risk MPTMC and to provide evidence-based medicine for the revision of clinical guidelines. This study included 66 MPTMC patients with a total of 158 lesions, all of whom received MWA. We collected and retrospectively analyzed the patients' follow-up data before MWA, at 1, 3, 6, and 12 months posttreatment and every 6 months thereafter until 5 years posttreatment. We evaluated the MWA complication rate, technical success rate (TSR), lesion volume reduction rate (VRR), and complete disappearance rate (CDR) during follow-up and in those patients with tumor progression and delayed surgery. After 60 months of follow-up, all 158 lesions disappeared in 66 patients, and the volume was reduced from 43.82 mm3 to 0.00 mm3. The TSR and VRR were both 100%. The CDRs at 1 year, 2 years, and 3 years were 57.59%, 93.67%, and 100%, respectively. The complication rate was 3.03% (2/66), and the incidence of tumor progression was 3.03% (2/66), including one new intrathyroidal lesion and one cervical lymph node metastasis (LNM). These lesions were retreated with MWA, and the lesions disappeared during the follow-up period. Ultrasound-guided MWA for low-risk MPTMC is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance (AS). This study concludes that ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective and may serve as an alternative option for patients who refuse surgery or active surveillance. • Ultrasound-guided microwave ablation for low-risk multifocal papillary thyroid microcarcinoma is safe and effective. • During 5 years of follow-up, multifocal papillary thyroid microcarcinoma patients treated with microwave ablation had a favorable prognosis. • To provide evidence-based medicine for the revision of clinical guidelines.