Computed Tomography for Detecting Cervical Lymph Node Metastasis in Patients Who Have Papillary Thyroid Microcarcinoma with Tumor Characteristics Appropriate for Active Surveillance.

Background: The preoperative assessment of cervical lymph node metastasis (LNM) is considered a challenging clinical problem in papillary thyroid microcarcinoma (PTMC) patients. Ultrasonic examination is significant for the cervical LNM in PTMC patients, but there are difficulties and limitations in observing lymph nodes in the cervical central region. Objectives: To investigate the diagnostic value of dual-energy computed tomography (DECT) iodine for characterization of PTMC and better prediction of metastatic cervical lymph nodes of PTMC. Patients and Methods: Ninety-five patients with PTMC who underwent DECT examinations were retrospectively enrolled in the study. The iodine image morphological features of primary tumor were analyzed in the arterial phase and quantitative DECT parameters of the primary tumor were recorded in the arterial and venous phase. Chi-square test and independent-sample t test were performed to compare the differences of morphological features and quantitative parameters of tumors between LNM and non-LNM groups. Receiver operating characteristic curves were generated to assess the diagnostic performance of each DECT parameter and their combinations. Results: Six primary tumor morphological features of the LNM group demonstrated significant differences compared with the non-LNM group (all p < 0.05). Normalized iodine concentration (NIC) and normalized CT value in the LNM group were significantly higher than those of the non-LNM group in both arterial and venous phase, respectively (all p < 0.001). The area under the curve (AUC) was improved from 0.814 to 0.843 after adding maximum diameter compared with incomplete thyroid capsule alone. In addition, the combination of NICs in arterial and venous phases had higher AUC than other quantitative parameters. Conclusion: Morphological features and quantitative parameters of DECT are valuable for predicting cervical LNM in patients with PTMC.

Background:Cervical lymph node (LN) metastasis of papillary thyroid carcinoma (PTC) is critical for treatment and prognosis. To examine the feasibility of MRI radiomics to preoperatively predict cervical LN metastasis in patients with PTC.Methods:Between January 2015 and March 2018, a total of 61 patients with pathologically confirmed PTC were analyzed retrospectively. The patients were divided into cervical LN metastasis group (n = 37) and no cervical LN metastasis (n = 24). T2WI and T2WI-fat-suppression (T2WI-FS) images were collected. A number of radiomic features were automatically extracted from the largest section of tumor. Three types of classifier (the random forests, the support vector machine classifier and the generalized linear model) based on T2WI and T2WI-FS images of cervical LN metastasis and no cervical LN metastasis were constructed and evaluated with a nested cross-validation scheme.Results:Radiomic features extracted from T2WI images were more discriminative than T2WI-FS images. The random forests model showed the best discriminate performance with the highest area under the curve (0.85, CI:0.76 -1), accuracy (0.87), sensitivity (0.83), specificity (1.00), positive predictive value (PPV = 1.00) and negative predictive value (NPV = 0.88).Conclusion:MRI radiomics analysis based on conventional T2WI and T2WI-FS can predict cervical LN metastasis in patients with PTC, and the radiomics is shown to be an assistant diagnosis tool for radiologists.

Objective: To investigate the correlation between cervical lymph node skip metastasis with ultrasonographic characteristics of papillary thyroid micro- carcinoma (PTMC). Methods: We reviewed ultrasonographic features of 385 primary PTMC and cervical lymph node metastasis, confirmed by pathology in Tianjin Medical University Cancer Institute and Hospital, to evaluate the efficacy of ultrasonography in the diagnosis of cervical lymph node metastasis of PTMC patients. The relationship between ultrasonographic features of primary lesions and skip metastasis of cervical lymph nodes was analyzed by χ(2) test and multiple factor Cox regression. Results: Among the 385 cases of PTMC patients with cervical lymph node metastasis, 231 cases were central lymph node metastasis alone, 31 cases were lateral cervical lymph node metastasis alone, 123 cases were both central and lateral cervical lymph node metastasis. Among the 354 cases without skip metastasis of cervical lymph nodes, 48 cases were level Ⅱ, 92 cases were level Ⅲ, 83 cases were level Ⅳ, 9 cases were level Ⅴ, 354 cases were level Ⅵ. Among the 31 cases with skipping metastasis of cervical lymph nodes, 12 cases were level Ⅱ, 14 cases were level Ⅲ, 14 cases were level Ⅳ, 1 case was level Ⅴ. The sensitivity and specificity of preoperative ultrasonography in the diagnosis of central cervical lymph node metastasis were 46.3% and 66.7%, respectively, and those of lateral cervical lymph node were 91.0% and 87.8%, respectively. Univariate analysis showed that the abutment/perimeter, diameter and location of PTMC were significantly associated with skip metastasis (P<0.05), multivariate analysis showed that abutment/perimeter and location of PTMC were significantly associated with skip metastasis (P<0.05). Conclusions: The sensitivity and specificity of preoperative ultrasound diagnosis for lateral cervical lymph node metastasis of PTMC is higher than that of central metastasis. PTMC with abutment/perimeter ≥1/4 and upper portion location are prone to skip metastasis.

The rate of cervical central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC) patients is relatively high. It is controversial that patients with clinically lymph node (LN)-negative entail prophylactic central neck dissection (pCND). The objective of this study was to develop and validate a predictive nomogram incorporating both radiomics signatures and ultrasonic features to aid in the individualized, preoperative assessment of central cervical LN metastasis in patients with clinically node-negative PTMC. A total of 266 patients, each with a single malignant thyroid nodule, were enrolled and randomly split into a training set and a validation set at a ratio of 7:3. Radiomics signatures were constructed by applying the least absolute shrinkage and selection operator (LASSO) regression to features extracted from two-dimensional (2D) ultrasound (US) images. We then built three logistic regression models using clinical and US features (model 1), the radiomics signatures (model 2), and a combination of both (model 3). Finally, we presented the combined model as a nomogram and assessed its clinical utility with decision curve analysis (DCA). The highest diagnostic performance was achieved by model 3, which showed robust discrimination in the training [area under the curve (AUC) =0.892], internal validation (AUC =0.772), and external validation (AUC =0.842) sets, outperforming model 1 and model 2. A nomogram combining radiomics analysis based on US images of PTMC with clinical and imaging features showed a better diagnostic performance than conventional US imaging features alone in predicting metastatic central cervical LNs preoperatively in clinically LN-negative patients with PTMC and could assist in making advice associated with treatment plan.

BackgroundTo investigate the risk factors of cervical lymph node (LN) metastasis in papillary thyroid microcarcinoma (PTMC) patients.MethodsWe retrospectively analyzed the clinicopathologic data of all patients who received standard lobectomy for PTMC at our institution between October 2017 and January 2019. Central LNs were dissected in all patients. Lateral LNs were dissected if metastasis to the lateral LNs was suggested based on pre-op fine-needle aspiration biopsy. The relationship between variables available prior to surgery and cervical LN metastasis was examined using multivariate regression.ResultsPost-op pathologic examination revealed cervical LN metastasis in 79 (29.5%) patients. Seventy subjects had metastasis only to central LNs, and 4 (1.5%) patients had metastasis only to lateral LNs. Five patients had metastasis to both central and lateral LNs. In comparison to patients without cervical LN metastasis, those with LN metastasis were significantly younger (40.63 ± 13.07 vs. 44.52 ± 12.23 years; P = 0.021) and had significantly larger tumor diameter on pathology (6.7 ± 2.2 vs. 5.9 ± 2.4 mm; P = 0.010). Multivariate regression analysis identified the following independent risks for cervical LN metastasis: male sex (OR 2.362, 95%CI 1.261~4.425; P = 0.007), age (OR 0.977, 95%CI 0.956~0.999; P = 0.042) and ultrasound tumor diameter at > 5 mm (OR 3.172, 95%CI 1.389~7.240; P = 0.006).ConclusionCervical LN metastasis occurs in a non-insignificant proportion of PTMC patients. Independent risks included male sex, younger age and larger tumor diameter on ultrasound.

Objective: To investigate the rationality of management of active surveillance for papillary thyroid microcarcinoma (PTMC) and the main indications for active surveillance for PTMC. Methods: In this study, two criteria were used to evaluate patients with PTMC: low-risk PTMC conditions defined by Kuma hospital and Chinese Association of Thyroid Oncology (CATO) consensus on PTMC management of active surveillance. The patients had received surgical treatment. Clinicopathological characteristics and prognosis of the patients in different groups were compared. Results: A total of 778 patients were enrolled in the study, 565 (72.6%) of them met Kuma screening criteria and only 112 (14.4%) met CATO screening criteria. Kuma low-risk subgroup had lower incidence of cervical lymph node metastasis than Kuma high-risk PTMC subgroup(30.6% vs 47.9%, P<0.05). There were significant differences in multifocal lesions(6.3% vs 16.4%), extrathyroidal extension (1.8% vs 7.5%) and cervical lymph node metastasis(19.6% vs 38.0%) between low-risk and high-risk CATO PTMC subgroups. Patients in the CATO low-risk PTMC subgroup had lower recurrence and longer disease-free survival (DFS) than those in the CATO high-risk PTMC subgroup. But there was no significant difference in recurrence or DFS between Kuma low-risk and high-risk Kuma PTMC subgroups.The Chi-square test of Fisher's exact probabilities test was used to compare clinicopathological characteristics of patients between different groups.Rates of disease-free survival were calculated using the Kaplan-Meier method. Conclusion: CATO screening criteria is relatively strict and may be more suitable for Chinese patients with active surveillance for PTMC.

Papillary thyroid microcarcinoma (PTMC) usually has an excellent prognosis. To evaluate the three-dimensional structures of PTMCs, using serial neck ultrasonography (US) in patients under active surveillance. A retrospective cohort study. In total, 192 patients diagnosed with PTMC under active surveillance for >1 year were included in a median 30-month follow-up. Changes in tumor size were evaluated not only using the maximal tumor diameter but also the tumor volume. The median age of patients was 51.3 years and 145 patients (76%) were female. The median initial maximal tumor diameter and tumor volume were 5.5 mm and 48.8 mm3, respectively. The tumor size increased in 27 patients (14%); 23 patients showed a tumor volume increase >50% without a maximal diameter increase of ≥3 mm. The other four patients had both an increasing tumor volume and increasing maximal tumor diameter ≥3 mm. One patient (0.5%) had newly appeared cervical lymph node (LN) metastasis at 3 years after the initial diagnosis. There were no significant risk factors associated with increased tumor size, such as age, sex, or Hashimoto thyroiditis. Twenty-four patients (13%) underwent delayed thyroid surgery at a median of 31.2 months and seven (29%) had cervical LN metastasis on pathologic examination. Some PTMCs could grow significantly after a relatively short period of active surveillance. We also found that the change in tumor volume was more sensitive to detect tumor progression than the change in the maximal tumor diameter.

Background: Active surveillance (AS) of papillary thyroid microcarcinomas (PTMC) is emerging as an alternative to immediate surgery. While thermal ablation has also shown promise for low-risk PTMC, it has not been prospectively studied in patients appropriate for AS. This study aimed to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for tumor control and quality of life (QoL) management in patients with PTMC who favored AS over immediate surgery. Methods: This prospective clinical trial was conducted at a single tertiary referral hospital from 2018 to 2021. Of 227 adult patients aged ≤60 years with low-risk unifocal PTMC favoring AS over immediate surgery, 100 patients underwent RFA for their management. The primary endpoint was the disease progression rate, and secondary endpoints were technical success, volume reduction rate (VRR), complication rates, and QoL. Results: The median age of the study population was 42 years (range, 27-59 years), and 83% (83/100, [CI: 66.1-100]) were female. The median follow-up was 30 months (range, 12-56 months). All 100 patients underwent RFA with technical success. Most of the ablation zones showed continuous volume reduction, and 95.9% (94/98, [CI: 77.5-100.0]) showed complete disappearance at the last follow-up. The median VRR was 100.0% at 1-year follow-up and persisted throughout the last follow-up. The cumulative disease progression rate among 98 patients who underwent at least 1-year follow-up was 3.1% (3/98, [CI: 0.6-9.0]); one patient had lymph node metastasis (treated with surgery), and two patients had new PTMC (1 treated with RFA, 1 ongoing AS). Major complications were not observed. Psychological (baseline vs. last follow-up, 7.3 vs. 8.0, p = 0.002) and social (8.0 vs. 8.7, p = 0.005) QoL scores significantly improved during follow-up without compromising physical QoL (8.6 vs. 8.5, p = 0.99). Conclusions: RFA can be a reasonable strategy for effectively and safely controlling tumors and improving QoL in non-elderly patients with low-risk PTMC appropriate for AS. Clinical Trial registration: This trial is registered with ClinicalTrials.gov: NCT03432299.

Analysis of the risk factors for central lymph-node metastasis of cN0 papillary thyroid microcarcinoma: A retrospective study

Ultrasound-Guided Radiofrequency Ablation of Low-Risk Papillary Thyroid Microcarcinoma: a Prospective Study

BackgroundEstimates of cervical lymph node (LN) metastasis in patients with middle and lower thoracic esophageal squamous cell carcinoma (ESCC) are important. A nomogram is a useful tool for individualized prediction.MethodsA total of 235 patients were enrolled in this study. Univariate and multivariate analyses were performed to screen for independent risk factors and construct a nomogram to predict the risk of cervical LN metastasis. The nomogram performance was assessed by discrimination, calibration, and clinical use.ResultsTotally, four independent predictors, including the maximum diameter of tumor, paraesophageal lymph node status, recurrent laryngeal nerve lymph node status, and the CT-reported cervical LN status, were enrolled in the nomogram. The AUC of the nomogram model in the training and validation dataset were 0.833 (95% CI 0.762–0.905), 0.808 (95% CI 0.696–0.920), respectively. The calibration curve demonstrated a strong consistency between nomogram and clinical findings in predicting cervical LN metastasis. Decision curve analysis demonstrated that the nomogram was clinically useful.ConclusionWe developed a nomogram that could be conveniently used to predict the individualized risk of cervical LN metastasis in patients with middle and lower thoracic ESCC.

ObjectivesThe aim of the current study was to evaluate the value of preoperative 18F-FDG (FDG) PET/CT in predicting cervical lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC).MethodsOne hundred and ninety-three newly diagnosed PTC patients (M: F = 25:168, age = 46.8 ± 12.2) who had undergone pretreatment FDG PET/CT and had neck node dissection were included in this study. The FDG avidity of the primary tumor and the SUVmax of the primary tumor (pSUVmax) were analyzed for prediction of LN metastasis. Detectability by ultrasonography (US) and FDG PET/CT for cervical LN metastasis were also assessed and compared with the pSUVmax.ResultsThe FDG avidity of the primary tumor was identified in 118 patients (FDG avid group: 61.0%, M: F = 16:102, age 47.0 ± 12.7 years) and pSUVmax ranged from 1.3 to 35.6 (median 4.6) in the FDG avid group. The tumor size in the FDG avid group was bigger and there was a higher incidence of LN metastasis compared to the FDG non-avid group (0.93 vs. 0.59 cm, p <0.001 and 49.2 vs. 33.3%, p <0.05). In the FDG avid group, patients with LN metastasis had higher pSUVmax than patients without LN metastasis (8.7 ± 8.3 vs. 5.7 ± 5.1, p <0.001). The incidence of central LN metastasis in patients with a pSUVmax >4.6 was 54%; however, the detectability of central LN metastasis by US and FDG PET/CT were 10.3% and 3.6%, respectively.ConclusionA high FDG avidity of the primary tumor was related to LN metastasis in PTC patients. Therefore, patients with a high pSUVmax should be cautiously assessed for LN metastasis and might need a more comprehensive surgical approach.

BackgroundCervical lymph node metastasis (LNM) is an important prognostic factor for patients with non-small cell lung cancer (NSCLC). We aimed to develop and validate machine learning models that use ultrasound radiomic and descriptive semantic features to diagnose cervical LNM in patients with NSCLC.MethodsThis study included NSCLC patients who underwent neck ultrasound examination followed by cervical lymph node (LN) biopsy between January 2019 and January 2022 from three institutes. Radiomic features were extracted from the ultrasound images at the maximum cross-sectional areas of cervical LNs. Logistic regression (LR) and random forest (RF) models were developed. Model performance was assessed by the area under the curve (AUC) and accuracy, validated internally and externally by fivefold cross-validation and hold-out method, respectively.ResultsIn total, 313 patients with a median age of 64 years were included, and 276 (88.18%) had cervical LNM. Three descriptive semantic features, including long diameter, shape, and corticomedullary boundary, were selected by multivariate analysis. Out of the 474 identified radiomic features, 9 were determined to fit the LR model, while 15 fit the RF model. The average AUCs of the semantic and radiomics models were 0.876 (range: 0.781–0.961) and 0.883 (range: 0.798–0.966), respectively. However, the average AUC was higher for the semantic-radiomics combined LR model (0.901; range: 0.862–0.927). When the RF algorithm was applied, the average AUCs of the radiomics and semantic-radiomics combined models were improved to 0.908 (range: 0.837–0.966) and 0.922 (range: 0.872–0.982), respectively. The models tested by the hold-out method had similar results, with the semantic-radiomics combined RF model achieving the highest AUC value of 0.901 (95% CI, 0.886–0.968).ConclusionsThe ultrasound radiomic models showed potential for accurately diagnosing cervical LNM in patients with NSCLC when integrated with descriptive semantic features. The RF model outperformed the conventional LR model in diagnosing cervical LNM in NSCLC patients.

To investigate the qualitative and quantitative characteristics of contrast-enhanced ultrasound (CEUS) in assessing cervical lymph node metastasis from papillary thyroid carcinoma (PTC) and to evaluate its value in the preoperative diagnosis of cervical lymph node metastasis from PTC. A total of 55 lymph nodes in 46 patients were enrolled retrospectively, including 29 metastases from PTC and 26 normal/reactive ones. All lymph nodes were evaluated by conventional ultrasound (US) and CEUS before biopsy or surgery. A receiver operating characteristic curve analysis was used to analyze the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of US and CEUS features in the diagnosis of lymph node metastasis as well as the overall diagnostic performance of US, CEUS, and a combination of the two. Significant differences were found in the enhancement direction, enhancement type, and enhancement range between metastatic and normal/reactive lymph nodes on CEUS (P < .05). Quantitative CEUS parameters were not statistically significant (P > .05). The combination of US and CEUS had the highest diagnostic accuracy (92.7%) compared with US (80.8%) and CEUS (89.1%) alone in the diagnosis of lymph node metastasis from PTC. The characteristics of cervical lymph node metastasis from PTC on CEUS include centripetal perfusion, peripheral or mixed enhancement, and an enlarged range on CEUS compared with US, and the first feature was the most meaningful. The combination of CEUS and US is a promising imaging tool for the preoperative diagnosis of cervical metastatic lymph nodes in patients with PTC.

Background: Some papillary thyroid microcarcinomas (PTMCs) may progress with tumor enlargement or development of new lymph node (LN) metastasis during active surveillance (AS). This study evaluated the relevant predictors of disease progression, especially new cervical LN metastasis. Methods: This was a long-term follow-up study conducted using a previous multicenter cohort of AS in Korea. After excluding 54 (14.2%) patients with a short follow-up duration, 326 PTMC patients were evaluated for tumor kinetics, including changes in tumor volume (TV) and TV doubling time (TVDT). Results: During a median follow-up duration of 4.9 years, 17 (5.2%, 95% confidence intervals [CI] 2.7-7.6%) patients showed a maximal diameter increase of ≥3 mm after a median of 4.0 years follow-up, while 9 (2.8%, CI 1.0-4.5%) developed new LN metastasis after a median of 2.2 years follow-up. New cervical LN metastasis occurred exclusively of a maximal diameter increase of ≥3 mm. The prevalence of new development of LN metastasis was higher in patients with TVDT <5 years (7.4%) than in those with TV ≥50% (3.2%). Furthermore, only TVDT <5 years was significantly associated with LN metastasis (p = 0.002). In univariate and multivariate analyses, TVDT <5 years was an independent risk factor for disease progression with respect to new development of LN metastasis (hazard ratio [HR] = 6.51, CI 1.73-24.50; p = 0.002) and tumor enlargement (HR = 20.89, CI 5.78-75.48; p < 0.001). Finally, 86 (22.6%) patients underwent delayed surgery, and the most common reason was patient anxiety. Conclusions: TVDT <5 years is a predictor of disease progression during AS in terms of new LN metastasis development as well as tumor enlargement. Determination of TVDT in the early phase of AS could help in predicting disease progression, tailoring follow-up intensity of AS and in determining if early surgical intervention is needed.