Papillary Thyroid Microcarcinoma Patients Research Articles

Clinical feasibility of imaging with indocyanine green combined with methylene blue for sentinel lymph node identification in papillary thyroid microcarcinoma

Objective:To explore the value of indocyanine green（ICG） combined with methylene blue in the identification of sentinel lymph nodes（SLNs） in patients diagnosed with papillary thyroid microcarcinoma（PTMC）. Methods:Ninety patients were enrolled and were randomized into group A and group B with 45 patients in each group. ICG combined with methylene blue were injected into the thyroid in group A, and only methylene blue were injected into thyroid in group B. Blue-stained or fluorescent nodes observed using near-infrared fluorescence imaging systems were defined as SLNs. After SLNs were removed, central lymph nodes（CLNs） dissection was completed in both groups. The pathological data and postoperative outcomes were compared between two groups. Results:There were significantly more SLNs（2.93/2.17） and CLNs（4.51/3.89） were dissected in group A than in group B（P<0.05）. There were no significant differences in sensitivity, accuracy and the false-negative rate according the SLNs in two groups（P>0.05）, but group A has higher sensitivity and accuracy rates, and lower false-negative rate. There were no significant differences in the amount of blood loss, the amount of lymphatic drainage, and incidence of hoarseness and lymphatic leakage in two groups（P>0.05）. In group A, the operating time was longer, and the rate of hypoparathyroidism was lower（P<0.05）. Conclusion:Sentinel lymph nodes biopsy using ICG combined with methylene blue is feasible and safe for SLNs identification in PTMC patients. It is also clinically significant for the parathyroid gland protection.

Prevalence and predictor for malignancy of contralateral thyroid nodules in patients with unilateral PTMC: a systematic review and meta-analysis.

BackgroundThe presence of clinically negative nodules on the contralateral lobe is common in patients with unilateral papillary thyroid microcarcinoma (PTMC). The appropriate operational strategies of contralateral thyroid nodules remain controversial. In this study, we analyzed clinical features that could be predictors for malignancy of contralateral thyroid nodules coexisting with diagnosed unilateral PTMC.MethodsThe literatures published from January 2000 to December 2019 were searched in PubMed, Cochrane Library, Embase, Web of Science, CNKI, and Wan Fang database. Odds ratio (OR) with 95% CI was used to describe categorical variables. Heterogeneity among studies was examined by the Q test and I2 test; potential publication bias was detected by Harbord test and ‘trim and fill’ method.ResultsIn this meta-analysis, 2541 studies were searched and 8 studies were finally included. The results showed that the rate of carcinoma in contralateral nodules was 23% (OR = 0.23, 95% CI = 0.18–0.29). The pooled data indicated that contralateral malignancy was not associated with age, gender, primary lesion size, ipsilateral central lymph node metastasis and multifocality of contralateral lesion. The following variables have correlations with an increased risk of contralateral malignancy: multifocality of primary carcinomas (OR = 3.93, 95% CI = 2.70–5.73, P < 0.0001), capsular invasion (OR = 1.61, 95% CI = 1.10–2.36, P = 0.01), and Hashimoto's thyroiditis (OR = 1.57, 95% CI = 1.13–2.20, P = 0.008).ConclusionsBased on our meta-analysis, the rate at which contralateral malignancies are preoperatively misdiagnosed as benign is 23%. The risk factors for contralateral malignancy in unilateral PTMC patients with contralateral clinical negative nodules include multifocality of primary carcinomas, capsular invasion, and Hashimoto's thyroiditis.

Treatment strategies and predicting lymph node metastasis in elderly patients with papillary thyroid microcarcinoma.

This study aims to explore the prognostic variables for elderly papillary thyroid microcarcinoma (PTMC) patients as well as create a nomogram that could predict the occurrence of cervical lymph node metastasis (CLNM) on the basis of a large population database with high quality.A total of 5165 PTMC patients from Surveillance, Epidemiology, and End Results database database were enrolled in the study. In the meantime, we retrospectively collected 205 PTMC patients who underwent thyroidectomy in our medical center as an external control to test the accuracy of the model. The independent predictors of survival were identified by multivariate Cox regression analysis. Risk factors were selected as nomogram parameters to develop a model to predict CLNM. The C-index and calibration plots were used to evaluate CLNM model discrimination. The predictive nomogram was further validated in the external validation set.76.8% of the enrolled patients underwent thyroidectomy. Overall survival and cancer-specific survival were significantly better in patients who underwent surgery than in those who did not (P < .001). Sex, tumor size, and extent of tumor were included in a multivariable logistic regression model to predict lymph node metastasis. The nomogram had good discrimination with a C-index of 0.71. The calibration curves showed perfect agreement between nomogram predictions and actual observations.Elderly PTMC patients who received a surgical approach without radiotherapy showed survival advantage than those with other treatment strategies. Moreover, a nomogram model was established to predict the risk of CLNM, which will help clinicians in making treatment decisions.

Added Value of Postoperative Radioiodine Scan for Staging and Risk Stratification in Papillary Thyroid Microcarcinoma.

ObjectiveThe complete staging and risk stratification of Papillary thyroid microcarcinoma (PTMC) is usually not done due to its theoretically low recurrence rates. This study aimed to determine the value of postoperative radioiodine diagnostic scan and SPECT/CT for the accurate staging and risk stratification in PTMC patients.MethodologyThis study was a retrospective review of PTMC patients from January 2014 to May 2017 who underwent I-131 scans. All PTMC patients were initially staged by the 8th edition AJCC/TNM staging system and risk-stratified, based on clinical information, histopathology and stimulated thyroglobulin (sTg). After I-131 scan, staging and risk stratification were re-assessed. The proportion of patients who ended up with a higher stage and risk stratification were reported.Results and ConclusionFifty-two patients were included. The overall upgrading of cancer stage was 7.7 %. The overall higher risk stratification was 19.2% with radioiodine-avid lymph node, lung, and bone metastases. Neck and paratracheal node metastases were found in 37.3% of the initial low-risk patients with sTg less than 5 ng/mL. Lung metastasis was found in the initial intermediate-risk patient. The I-131 scan helps to localize metastatic lesions and results in a higher stage in 50% of the initial high-risk patients. This study provides some evidence showing the value of postoperative radioiodine WBS for accurate staging and risk stratification in PTMC patients. Larger studies with analytical design should be further performed to prove its significant utility.

Value of Combining Clinical Factors, Conventional Ultrasound, and Contrast-Enhanced Ultrasound Features in Preoperative Prediction of Central Lymph Node Metastases of Different Sized Papillary Thyroid Carcinomas.

PurposeEarly and accurate preoperative diagnosis of central lymph node metastasis (CLNM) is crucial to improve surgical management of patients with clinical lymph node-negative papillary thyroid carcinoma (PTC). Towards improving diagnosis of CLNM, we assessed the value of combining preoperative clinical characteristics, conventional ultrasound, and contrast-enhanced ultrasound (CEUS) in preoperative prediction of CLNM of different sized PTCs.Patients and MethodsPatients were divided according to tumor size: a PTC group (>10 mm) and a papillary thyroid microcarcinoma (PTMC) group (≤10 mm). We retrospectively analyzed the clinical and ultrasonographic features of 120 PTC patients and 165 PTMC patients. Multivariate logistic regression analysis was used to screen independent risk factors and establish prediction models. Receiver operating characteristic curves were used to determine the best cut-off values for continuous variables and assess the performance of prediction models.ResultsIndependent risk predictors of CLNM for the PTC group were extrathyroidal extension in CEUS (OR=7.923), tumor size >14 mm (OR=5.491), and multifocality (OR=3.235). For the PTMC group, the independent risk factors were the distance from the thyroid capsule =0 mm (OR=4.629), male (OR=3.315), tumor size >5 mm (OR=3.304), and microcalcification (OR=2.560). The predictive model of combined method had better performance in predicting CLNM of PTC compared with models based on CEUS and conventional ultrasound alone (area under the curve: 0.832 vs 0.739, P=0.0011; 0.832 vs 0.678, P=0.0012). For PTMC, comparing with CEUS, the combined method and conventional ultrasound performed better than CEUS alone in predicting CLNM (area under the curve: 0.783 vs 0.636, P=0.0016; 0.738 vs 0.636, P=0.0196).ConclusionThe predictive models of combined method obtained from significant preoperative clinical and ultrasonographic features can potentially improve the preoperative diagnosis and individual treatment of CLNM in patients with PTC and PTMC. CEUS may be helpful in predicting CLNM of PTC, but CEUS would be ineffective in predicting CLNM of PTMC.

Clinical and ultrasonic features of papillary thyroid microcarcinoma and risk factors for central lymph node metastasis

Objective:To investigate the clinical and ultrasonic features of papillary thyroid microcarcinoma （PTMC） and the risk factors of central lymph node metastasis （CLNM）, to provide help for individualized treatment. Methods:One hundred and eighty-five patients with PTMC confirmed by surgery and pathology and underwent prophylactic CLN dissection were retrospectively analyzed. According to lymph node metastasis, patients were divided into metastasis group and non metastasis group. The size, shape, echo, aspect ratio, edge, protruding capsule, nodule location, calcification and calcification were analyzed. The relationship between clnm and ultrasonographic features, sex, age, single/multiple, whether or not with Hashimoto thyroiditis was analyzed. Results:Among 185 patients with PTMC, 55 cases had lymph node metastasis, and the metastasis rate was 30.0%. In univariate analysis, clnm of PTMC was significantly correlated with gender, age, tumor size, protruding capsule, type of calcification and single / multiple （all P<0.05）. In multivariate logistic regression analysis, tumor size, single/multiple, protruding capsule, gender and age were the risk factors of clnm. According to the ROC curve, when the age was 49.5 years old and the mass size was 4.8 mm, the diagnostic test yoden index reached the maximum value. Conclusion:When the risk factors of male, ≤49.5 years old, tumor size≥4.8 mm, multiple and protruding capsule appeared in PTMC patients, preventive CLN clearance should be taken actively.

Choosing Optimal Microcarcinoma Patients for Active Surveillance Study (Compass): Effectiveness Evaluation of a Preoperative Clinical Framework

ObjectiveActive surveillance (AS) is a management alternative for patients with low-risk papillary thyroid microcarcinoma (PTMC). To decide the best candidates for AS, clinicians can use a framework to classify PTMC patients as ideal, appropriate, or inappropriate. This study aimed to explore the correlation between the framework categories and surgical pathology. MethodsThis multicenter retrospective study was conducted between 2014 and 2016. We included 1997 patients who underwent thyroid surgery for the first time due to suspected PTMC and were confirmed as PTMC by postoperative pathology. The consistency of modified preoperative risk stratification and the pathologic condition were evaluated using a consistency ratio and the Kappa coefficient. Stratified analysis was also performed to test consistency in different age groups. ResultsBased on the decision-making framework, 558 (27.9%) patients could receive AS while 810 (40.6%) patients did not require immediate surgery according to the actual postoperative pathology. The sensitivity, false-positive rate, specificity, false-negative rate, and consistency rate were 82.39%, 56.91%, 43.09%, 17.61%, and 66.45%, respectively. The Kappa value was 0.268. Stratified analysis showed that the sensitivity was 87.7% among patients aged 18 to 59 years. In the group aged ≥60 years, the specificity was up to 87.5%, but the sensitivity was low. ConclusionThe results of the modified risk-stratified clinical decision-making framework did not have a high consistency with the postoperative results. However, the framework showed a good effect in selecting patients for immediate surgery in the younger group and patients for AS in the older group.

Analysis of Curative Effect and Influencing Factors of N1 Stage Papillary Thyroid Micro-Carcinoma and Papillary Thyroid Non-Micro Carcinoma After Initial Radioactive Iodine Ablation Therapy.

ObjectiveTo compare the efficacy and influencing factors of initial radioactive iodine (RAI) ablation therapy for postoperative N1 stage papillary thyroid micro-carcinoma (PTMC) and papillary thyroid non-micro carcinoma (PTC), and to explore the necessity of RAI for N1 stage PTMC.MethodsA retrospective analysis of patients with N1 stage papillary thyroid cancer who underwent RAI in our department from January 2018 to June 2019. According to the tumor diameter, papillary thyroid carcinoma was divided into PTMC group (≤ 1.0cm) with 129 patients and PTC group (> 1.0 cm) with 214 patients. According to the 2015 ATA guidelines, the patient’s treatment response was evaluated 6–8 months after discharge from the hospital: excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), and structural incomplete response (SIR). IDR, BIR, and SIR were classified into NER group. Chi-squared test, independent sample t-test, Mann–Whitney U test, and binary logistic regression analysis were used to compare the differences between PTMC and PTC patients.ResultsThe ps-Tg of the PTMC group was significantly lower than that of the PTC group (P = 0.001), and the ER ratio of the PTMC group was higher (χ2 = 5.445, P < 0.05). The ER ratio of PTMC patients in the N1a group was significantly higher than that of PTC patients (80%, 66.7%, χ2 = 4.076, P < 0.05), while the ER ratio of PTMC in the N1b group was not significantly different from that of PTC. Gender, N stage, and ps-Tg were found to be independent factors of RAI treatment response.ConclusionThe efficacy of the initial RAI of PTMC patients was significantly better than that of PTC patients. There was no significant difference in the efficacy of RAI between males with PTMC, N1b stage, ps-Tg ≥ 5.87ng/mL and PTC patients, which suggested that RAI is necessary for these patients.

A Comparison of the Seventh and Eighth Editions of the AJCC Staging Systems to Predict Recurrence in Papillary Thyroid Microcarcinoma.

The incidence of papillary thyroid microcarcinoma has been constantly rising in recent decades. The tumor, node, metastasis staging system is designed to predict prognosis in patients with papillary thyroid carcinoma. Recent studies have shown that the American Joint Committee on Cancer (AJCC) 8th edition is superior to the 7th edition for predicting tumor recurrence in PTC patients. To date, whether the 8th edition is also better able to predict recurrence in papillary thyroid microcarcinoma (PTMC) remains unclear. We enrolled 1007 cases from our thyroid cancer database in the First Affiliated Hospital, Zhejiang University School of Medicine, from 1997 to 2011. Univariable and multivariate Cox hazard regression analyses were used to identify the association between variables and recurrence. Disease-free survival was calculated using the Kaplan-Meier method and compared using the log-rank test. A total of 1007 PTMC patients were enrolled, with a median follow-up of 67 months. Of 93 (9.2%) patients downstaged by the changes in versions, 49 (52.7%) were downstaged because the age-at-diagnosis cut-off used for staging increased from 45 to 55years, while 35 (37.6%) were downstaged due to the weakening of the effects of lymph node metastasis. The recurrence rate of PTMC was 4.17%. Univariate Cox hazards regression analyses showed that TNM stage according to the AJCC 8th edition was significantly associated with recurrence, while the recurrence survival curves showed that TNM stage (stage I vs. stage II-IV) according to the AJCC 8th edition, but not the 7th edition, was significantly associated with disease-free survival (p<0.05). The AJCC 8th edition has better ability to predict recurrence in PTMC patients than the 7th edition.

A Nomogram for Predicting Lateral Lymph Node Metastasis in Cases of Papillary Thyroid Micro-Carcinoma with Suspected Lymph Node Metastasis

The elevation for lateral lymph node metastasis (LLNM) plays an important role in therapeutic decision-making for thyroid carcinoma. A reliable forecasting model for LLNM in patients with papillary thyroid micro-carcinoma (PTMC) is needed, using clinicopathological characteristics. A total of 576 PTMC patients with suspicious lateral cervical lymph node (II, III, IV or V region) metastasis and known clinicopathological variables were randomly collected at Shenzhen Second People’s Hospital. Cervical lymph node status of every patient was assessed by ultrasonography (US). The patients in this cohort study underwent thyroidectomy and lateral neck lymph node dissection. Univariate analysis and logistic regression analysis were performed to screen out the predictive variables associated with LLNM, and a nomogram was constructed by integrating clinicopathological features collected in our study. The overall LLNM rate was 23.0% (133/576). After statistical analysis, central lymph node metastasis (CLNM), prelaryngeal lymph node metastasis (PLNM), bilateral lesions, tumor location in thyroid (upper or lower), and gross extrathyroidal extension (ETE) were found to be independent predictive factors for LLNM (P < 0.01). The nomogram built to predict LLNM in PTMC patients passed the calibration step and the area under the receiver operating characteristic curve was 0.967, which showed that the nomogram we used had a good predictive effect. The nomogram constructed in this study has a good predictive value for LLNM, which will help thyroid surgeons to make a more accurate surgical plan for patients with PTMC. A strict preoperative evaluation and total thyroidectomy and lateral neck dissection may be indicated when patients with PTMC have a high score.

Clinical management of low-risk papillary thyroid microcarcinoma

Papillary thyroid microcarcinoma (PTMC) is well known to have an indolent nature with an excellent prognosis. Surgery has been the standard treatment during the past several decades, with metastasis or recurrence being exceedingly rare. Active surveillance (AS) is a new risk-adapted approach alternative to surgery that involves just watching, but not giving any treatment unless needed, not addressing the tumor itself. The patients for whom AS is adopted spend their time "with tumors." In follow-up, it is possible that alarming factors such as tumor progression appear, causing anxiety about progression. Furthermore, endless follow-up is needed. However, considering the indolent nature and unfavorable events such as surgical complications caused by surgery, AS is a good management plan for selected PTMC patients. Decision making balancing between the prognosis and unfavorable events is needed for the treatment plan. Consideration of the factors and timing of surgical conversion is also needed. In this review article, how AS should be adopted as a new management option that is an alternative to surgery, which has been the absolute choice of treatment up to recently, is discussed. Concurrently, the characteristics of the two treatment strategies are reviewed, while introducing the background that explains how AS came to attention.

Preoperative risk factors and recommendations for surgical intervention in cN0 papillary thyroid microcarcinoma.

The evaluation and management of papillary thyroid microcarcinoma (PTMC) have always been challenging and controversial. Our retrospective study aimed to investigate the metastatic trend and risk factors of cN0 papillary thyroid microcarcinoma patients and provide advice for surgical strategies. The clinicopathological features of 556 cN0 PTMC patients undergoing thyroidectomy combined with central compartment dissection (CCD) were compared by the χ2 test and risk factors were identified by binary logistic regression analysis. Numbers of dissected lymph nodes (DLN) and metastatic lymph nodes (MLN) were analyzed using the Mann-Whitney U test to compare metastatic trends between different lobes. Male gender, tumor maximum diameter (TMD) larger than 5 mm, multifocality, and capsular/extracapsular invasion were metastatic risk factors of central compartment metastasis (CCM) (p<0.05). The number of DLN in the right level VI was larger than in the left (p<0.05), while the number of MLN was similar (p>0.05). The chance of CCM was higher when the number of DLN was larger than 5 (p<0.05). After identified metastatic trends and risk factors, we recommend surgery for patients deciding on aggressive treatment, especially for cases where a combination of risk factors is present. And to ensure no residual metastatic lymph nodes and reduce secondary surgery rates, adequate lymphadenectomy on the diseased side would be a better choice considering the standard of care.

Long-term follow-up results of PTMC treated by ultrasound-guided radiofrequency ablation: a retrospective study

Objectives To confirm the long-term efficacy and safety of radiofrequency ablation (RFA) for low-risk papillary thyroid microcarcinoma (PTMC). Methods We retrospectively reviewed data of 102 primary papillary thyroid carcinoma patients (82 women, 20 men; mean age: 43 [19] years) treated with radiofrequency ablation and thyroid-stimulating hormone (TSH) suppression therapy before December 2018. All patients were at high surgical risk or refused surgery. They were followed up at 1, 3, 6, 9, and 12 months and every 6–12 months thereafter using ultrasound and contrast-enhanced ultrasound. The volume and volume reduction ratio was calculated. Recurrence and lymph node or distant metastasis were evaluated. Results The mean initial tumor diameter was 0.50 (0.29) cm; the mean initial volume was 0.06 (0.09) mL. At 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after RFA, complete resorption rates were 0, 0, 9.8 (10/102), 33.3 (34/102), 91.2 (93/102), 96.1 (98/102), 99 (101/102), 100, and 100%, respectively. Two patients had developed ipsilateral neck lymph node metastasis in regions IV and VI at 30- and 18-month follow-ups, respectively. After RFA, 3/102 patients (2.9%) developed hoarseness—the main side effect. No life-threatening or delayed complications occurred. The TSH value in the initial period was 0.06 (0.02) µIU/mL; the rate of reaching the TSH target was 85.7%. The TSH value at follow-up was 1.47 (0.91) µIU/mL; the compliance rate was 99.3%. Conclusions Ultrasound-guided RFA for PTMC is highly effective and safe. RFA can serve as a minimally invasive treatment for PTMC patients who refuse surgery or active surveillance.

Risk factors of papillary thyroid microcarcinoma that predispose patients to local recurrence.

Currently, less aggressive treatment or even active surveillance of papillary thyroid microcarcinoma (PTMC) is widely accepted and recommended as a therapeutic management option. However, there are some concerns about these approaches. We investigated whether there are any demographic, clinical and ultrasound characteristics of PTMC patients that are easy to obtain and clinically available before surgery to help clinicians make proper therapeutic decisions. We performed a retrospective chart review of 5,021 patients with thyroid tumors surgically treated in one center in 2008-2018. Finally, 182 (3.62%) PTMC patients were selected (158 (86.8%) females and 24 (13.2%) males, mean age 48.8±15.4 years). We analyzed the disease-free survival (DFS) time of the PTMC patients according to demographic and histopathological parameters. Univariate and multivariate logistic regression analyses were used to assess the relationships of demographic, clinical and ultrasound characteristics with aggressive histopathological features. Age ≥55 years, hypoechogenicity, microcalcifications, irregular tumor shape, smooth margins and high vascularity significantly increased the risk for minimal extrathyroidal extension (minETE), lymph node metastasis (LNM), and capsular and vascular invasion (p<0.0001). Multivariate logistic regression analysis demonstrated a statistically significant risk of LNM (OR = 5.98, 95% CI: 2.32-15.38, p = 0.0002) and trends toward significantly higher rates of minETE and capsular and vascular invasion (OR = 2.24, 95% CI: 0.97-5.19, p = 0.056) in patients ≥55 years than in their younger counterparts. The DFS time was significantly shorter in patients ≥55 years (p = 0.015), patients with minETE and capsular and vascular invasion (p = 0.001 for all), patients with tumor size >5 mm (p = 0.021), and patients with LNM (p = 0.002). The absence of microcalcifications, irregular tumor shape, blunt margins, hypoechogenicity and high vascularity in PTMC patients below 55 years and with tumor diameters below 5 mm may allow clinicians to select individuals with a low risk of local recurrence so that they can receive less aggressive management.

Quality of Life in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Active Surveillance Versus Immediate Surgery

This study aimed to compare the quality of life (QoL) and psychological issues of patients with papillary thyroid microcarcinoma (PMC) who were under active surveillance (AS) and those who underwent immediate surgery (OP). This was a cross-sectional study conducted on 347 patients with low-risk PMC who were under AS (n = 298) or who underwent OP (n = 49). They were asked to complete two questionnaires (thyroid cancer-specific health-related QoL [THYCA-QoL] and the Hospital Anxiety and Depression Scale [HADS]). The results between the AS and OP groups were compared. The mean ages of patients in the AS and OP groups were 58.6±12.5 and 58.4±13.1 years (P =.94), respectively, and the male ratios were 34/298 (11%) and 2/49 (4.1%) (P =.14), respectively. The median follow-up periods from diagnosis in the AS and OP groups were 56.5 months (interquartile range [IQR], 32 to 88 months) and 84 months (IQR, 64 to 130 months) (P<.001), respectively. In the THYCA-QoL questionnaire, the OP group had more complaints about "voice" (P<.001), "psychological" (P =.025), "problems with scar" (P<.001), and "gained weight" (P =.047) than the AS group. Other scales of the THYCA-QoL were comparable in the two groups. In the HADS questionnaire, the AS group had significantly better anxiety (P =.020), depression (P =.027), and total scores (P =.014) than the OP group. PMC patients in the OP group had more complaints and were more anxious and depressed than the AS group. These findings suggest that AS is a reasonable alternative to surgery for patients with low-risk PMC from the point of view of QoL and psychology. AS = active surveillance; CI = confidence interval; HADS = Hospital Anxiety and Depression Scale; LT4 = levothyroxine; OP = immediate surgery; PMC = papillary microcarcinoma; PTC = papillary thyroid carcinoma; QoL = quality of life; STAI = State-Trait Anxiety Inventory; THYCA-QoL = thyroid cancer-specific health-related quality of life; TSH = thyrotropin.

Clinical and pathologic predictors of lymph node metastasis in papillary thyroid microcarcinomas

Papillary thyroid microcarcinoma (PTMC) has the highest incidence among all thyroid carcinomas. Although surgery is the primary treatment for PTMC, it inevitably leads to trauma and some complications. To formulate an optimal treatment strategy, we aim to clarify the risk factors for lymph node metastasis (LNM) in PTMC patients. This study retrospectively analyzed patients who underwent thyroidectomy during 1995–2015, and grouped them according to lymph node metastasis. Age, gender, tumor size, thyroid functions, Hashimoto's thyroiditis, multifocal tumor, extrathyroidal extensions, capsular invasion were analyzed. Of the 2434 PTMC subjects, proportion of patients with no LNM (NLNM), LNM, central LNM (CLNM), lateral LNM (LLNM), CLNM + LLNM were 82.9%, 17.1%, 7.0%, 7.6% and 2.5%. Patients with NLNM were older and had a lower proportion of males compared to patients with CLNM, LLNM and CLNM + LLNM (p < 0.05). The NLNM group also had a smaller size of ultrasound tumor, lower proportion of multifocal tumor and extrathyroidal extension compared to CLNM, LLNM and CLNM + LLNM groups (p < 0.05). On univariate analyses, male gender, age <45 years, tumor size of pathology (˃0.75 cm), multifocality, and extrathyroidal extension were significantly associated with LNM. Multivariate analyses revealed that male gender, age <45 years, multifocality were risk factors for LNM. In conclusion, PTMC patients with male gender, age <45 years and multifocality should be evaluated carefully for possible LNM.

Association of sonographic features and clinicopathologic factors of papillary thyroid microcarcinoma for prevalence of lymph node metastasis: a retrospective analysis.

The objective of the study was to develop an association between clinicopathologic and sonographic features of patients with papillary thyroid microcarcinoma and the prevalence of lymph node metastasis. Clinicopathologic and sonographic features of 415 patients of papillary thyroid microcarcinoma with (n = 102) or without (n = 313) lymph node metastasis were retrospectively reviewed. The thickness of the lymph node ≥ 6 mm with intra-lymph nodal occupying lesions considered lymph node metastasis. Also, it was considered metastasis if lymph node perfusion or blood flow defect was found with any thickness size. Univariate following multivariate analysis was performed for the prediction of sonographic features and clinicopathologic factors for the prevalence of lymph node metastasis. Male gender (p = 0.041), age < 45 years (p = 0.042), preoperative calcitonin > 65 pg/ mL (p = 0.039), nodule size > 5 mm in diameter (p = 0.038), bilaterality (p = 0.038), tumor capsular invasion (p = 0.048), cystic change (p = 0.047), and hyper vascularity (p = 0.049) of thyroid nodules were associated with lymph node metastasis. Also, thyroid nodules 5 mm and more in diameter may have high aggressiveness. These data helped the surgeon for individualized treatment in thyroid carcinoma and avoid unnecessary prophylactic surgery of the lymph node.

Predictors for central lymph node metastases in papillary thyroid microcarcinoma

In recent years, with the wide application of ultrasound in health examination, the incidence of papillary thyroid microcarcinoma（PTMC） is increasing rapidly. There is more controversy about whether prophylactic central lymph node dissection（PCND） should be performed in PTMC patients with clinical lymph node negative（cN0）. Some clinical and pathological factors were associated with central lymph node metastasis in patients with PTMC. This paper review the risk factors for predicting central lymph node metastasis so as to screen high-risk PTMC patients who need to receive PCND, and guide clinicians to choose reasonable individualized surgery.

Active surveillance of low-risk papillary thyroid microcarcinomas

In 1993, active surveillance of low-risk papillary thyroid microcarcinomas (PTMCs) started in Kuma Hospital, Kobe, Japan. It has spread globally after the publishing of American Thyroid Association (ATA) guidelines. During our hospital's active surveillance program, few patients (8.0%) showed tumor size enlargement ≥3 mm or the new appearance of node metastasis (3.8%) at 10-year follow-up. Conversion surgery was recommended for patients with disease progression. To date, no patients showed significant recurrence or metastasis or died with thyroid carcinoma when patients underwent active surveillance or after surgery due to PTMC progression. Unlike clinical papillary thyroid carcinoma (PTC), elderly patients' PTMCs were less progressive compared to those of young and middle-aged patients, indicating that elderly patients are strong candidates for the active surveillance of their PTMC. Although young patients' PTMCs are the most progressive, >50% and >75% of patients in their 20s and 30s would avoid conversion surgical treatment in their lifetime, respectively (according to estimated lifetime probability), indicating that such young patients are still candidates for active surveillance. It can thus be concluded that active surveillance is appropriate to be first management for PTMCs, based on the accumulation of favorable outcomes of PTMC patients who have undergone active surveillance, as well as the lower incidences of unfavorable events and lower medical cost than immediate surgery.

Predicting non-small-volume central lymph node metastases (>5 or ≥2 mm) preoperatively in cN0 papillary thyroid microcarcinoma without extrathyroidal extension.

The ability to identify patients with aggressive papillary thyroid microcarcinoma (PTMC) from the low-risk patients is critical to planning proper management of PTMC. Lymph node metastases showed association with recurrence and low survival rate, especially in patients with >5 or ≥2 mm metastatic lymph nodes. Therefore, this study aimed to investigate the preoperatively predictive factors of non-small-volume (metastatic lymph nodes >5 or ≥2 mm in size) central lymph node metastases (NSVCLNM) in PTMC patients. A total of 420 patients with clinically node-negative (cN0) PTMC without extrathyroidal extension underwent thyroidectomy plus central neck dissection (CND) between January 2013 and December 2015, were retrospectively analyzed. Of the 420 patients, 33 (7.9%) had NSVCLNM. The 5-year recurrence-free survival was significantly less in cN0 PTMC patients with NSVCLNM, when compared with patients without NSVCLNM (80.8% vs 100%, P < .001). Multivariate logistic regression revealed age ≤36 years (P < .001), male sex (P = .002), ultrasonic tumor sizes of >0.65 cm (P < .001), and ultrasonic multifocality (P = .039) were independent predictive factors of NSVCLNM. A prediction equation (Y = 1.714 × age + 1.361 × sex + 1.639 × tumor size + 0.842 × multifocality −5.196) was developed, with a sensitivity (69.7%) and a specificity (84.0%), respectively, at an optimal cutoff point of −2.418. In conclusion, if the predictive value was >−2.418 according to the equation, immediate surgery including CND rather than active surveillance might be considered for cN0 PTMC patients.