Central lymph nodes in frozen sections can effectively guide extended lymph node resection for papillary thyroid carcinoma.

OBJECTIVES: The scope of lateral neck lymph node dissection (LND) in papillary thyroid carcinoma (PTC) remains controversial. Our research aimed to explore the value of central lymph node metastasis (CLNM) in frozen sections for predicting neck lateral lymph node metastasis (NLLNM) and to guide clinical surgeons in performing surgical lymph node dissection. PATIENTS: A total of 275 patients with PTC with suspected 'Cervical lymph node metastasis (LNM, including CLNM and NLLNM)' underwent unilateral or bilateral thyroidectomy and an intraoperative frozen diagnosis of central lymph nodes (LNs), as well as central and neck lateral LND. Validity indices and consistency of central LNs in frozen sections were calculated. In total, 216 patients then met the inclusion criteria and were enrolled in the follow-up study. The clinical and pathological data of the patients were retrospectively analyzed. The relationship between the number, metastatic diameter, and the ratio of CLNM to NLLNM was investigated. RESULTS: CLNM in frozen and paraffin-embedded sections was associated with NLLNM. Univariate and multivariate analyses revealed the following risk factors for NLLNM metastasis: maximum diameter, total number, and ratio of metastatic LNs. A significant result was obtained when a cut-off value of 2.050 mm for the maximum metastatic diameter, 5.5 in the total number, and 0.5342 for the CLNM ratio level was used. Interaction term analyses showed that the association between the number of CLNM and NLLNM differed according to maximum diameter. CONCLUSION: Central LNs in frozen sections accurately predicted NLLNM. In patients with PTC with >5 CLNMs, ≥2 and ≤5 CLNMs and maximum metastatic diameter > 2 mm, neck lateral LND should be considered. Our findings will facilitate the identification of patients who are likely to benefit from extended lateral neck LND.

Predictive nomogram for central lymph node metastasis in papillary thyroid microcarcinoma based on pathological and ultrasound features.

Background: Central lymph node metastases (CLNM) in papillary thyroid microcarcinoma (PTMC) are common, but management through prophylactic central lymph node dissection (pCLND) remains controversial. In this study, the independent predictors of CLNM in PTMC were retrospectively studied based on ultrasound and pathological data, and we aim to establish the prediction model to predict CLNM in PTMC. Methods: This study included a total of 1,506 patients who underwent thyroid surgery for PTMC at the First Affiliated Hospital of Chongqing Medical University from 2015 to 2018. Ultrasound and clinicopathological features were summarized and analyzed. Univariate and multivariate analyses were performed to determine the risk factors associated with CLNM. The prediction model is established and verified according to the multivariate analysis results. The Kaplan-Meier curve was used to evaluate the effect of CLNM on survival. Results: The CLNM rate was 44.5% (670/1,506). Multivariate analysis showed that men, younger age, smaller diameter, ETE, microcalcification, without Hashimoto's thyroiditis, and multifocal were independent risk predictors of CLNM. Nomogram has a good discriminative ability (C-index: 0.755 in the validation group), and the calibration effect is good. In the DCA curve, the CLNM prediction model performed better net benefit given any high-risk thresholds. The median follow-up time was 30 months (12-59 months), 116 cases were lost, and the follow-up rate was 92.8% (1,506/1,622). Of the 1,506 patients included, 12 (0.8%) experienced recurrence. Conclusion: The likelihood of CLNM can be objectively quantified before surgery by using this reliable and accurate nomogram that combines preoperative ultrasound with clinicopathological features. Clinicians can use this nomogram to assess central lymph node status in patients with PTMC and consider prophylactic CND in patients with high scores.

Clinical significance of multi-genic assay in identifying aggressive papillary thyroid carcinoma.

BACKGROUND: A minority of papillary thyroid carcinoma (PTC) is highly aggressive, with rapid progression and a poor prognosis. This study investigated the ability of multi-genic assay to identify patients with aggressive PTC. PATIENTS AND METHODS: A total of 117 PTC patients treated at The First Affiliated Hospital of Chongqing Medical University with clinicopathological data and multi-genic assay results and 389 patients with complete data from The Cancer Genome Atlas (TCGA) database were included. The chi-square test was used to analyze the relationship between the multi-genic assay results and clinicopathological characteristics. Univariate and multivariate regression analyses were used to analyze the impact of various factors on prognosis. RESULTS: The median follow-up times of the local and TCGA cohorts were 30 months and 34 months, respectively. The results showed that central lymph node metastasis (P = 0.036), lateral lymph node metastasis (P = 0.003) and mutations in genes other than BRAFV600E (P = 0.002) were significantly associated with disease-free survival (DFS) in the local cohort, while the analysis of TCGA data showed that mutations in genes other than BRAFV600E were significantly related to poor prognosis (P = 0.029). According to univariate and multivariate analyses, mutations in genes other than BRAFV600E (P = 0.021) and lateral lymph node metastasis (P = 0.022) were independent factors for postoperative recurrence, as well as, mutations in genes other than BRAFV600E were an independent factor of survival (P = 0.047). CONCLUSIONS: The multi-genic assay was able to identify aggressive PTC, providing an effective biological basis for surgical management and postoperative treatment.

Relationship between subgroups of central and lateral lymph node metastasis in clinically node-negative papillary thyroid carcinoma.

BACKGROUND: Lymph node metastasis (LNM) of papillary thyroid carcinoma (PTC) has a certain regularity and occurs first to the central lymph node and then to the lateral lymph node. The pathway of PTC LNM can guide surgical prophylactic lymph node dissection (LND) for clinical surgeons. AIM: To investigate the relationship between subgroups of central LNM and lateral LNM in unilateral clinically node-negative PTC (cN0-PTC). METHODS: Data were collected for 1089 PTC patients who underwent surgical treatment at the Department of Endocrine and Breast Surgery of the First Hospital of Chongqing Medical University from January 2016 to December 2017. A total of 388 unilateral cN0-PTC patients met the inclusion criteria and were enrolled in this study. The clinical and pathological data for these 388 patients who underwent total thyroidectomy + central LND + lateral LND were retrospectively analyzed. The relationship between the central LNM and lateral LNM subgroups was investigated. RESULTS: The coincidence rate of cN0-PTC was only 30.0%.Optimal scaling regression analysis showed that sex (57.1% vs 42.9%, P = 0.026), primary tumor size (68.8% vs 31.2%, P = 0.008), tumor location (59.7% vs 40.3%, P = 0.007), extrathyroid extension (ETE) (50.6% vs 49.9%, P = 0.046), and prelaryngeal LNM (57.1% vs 42.9%, P = 0.004) were significantly associated with ipsilateral level-II LNM. Their importance levels were 0.122, 0.213, 0.172, 0.110, and 0.227, respectively. Primary tumor size (74.6% vs 30.2%, P = 0.016), pretracheal LNM (67.5% vs 32.5%, P < 0.001), and paratracheal LNM (71.4% vs 28.6%, P < 0.001) were significantly associated with ipsilateral level-III LNM. Their importance levels were 0.120, 0.408, and 0.351, respectively. Primary tumor size (72.1% vs 27.9%, P = 0.003), ETE (70.4% vs 29.6%, P = 0.016), pretracheal LNM (68.3% vs 31.7%, P=0.001), and paratracheal LNM (80.8% vs 19.2%, P < 0.001) were significantly associated with ipsilateral level-IV LNM. Their importance levels were 0.164, 0.146, 0.216, and 0.472, respectively. CONCLUSION: The LNM pathway of thyroid cancer has a certain regularity. For unilateral cN0-PTC patients with a tumor diameter > 2 cm and pretracheal or ipsilateral paratracheal LNM, LND at ipsilateral level III and level IV must be considered. When there is a tumor in the upper third of the thyroid with prelaryngeal LNM, LND at level II, level III and level IV must be considered.

Male Gender Is Associated with Lymph Node Metastasis but Not with Recurrence in Papillary Thyroid Carcinoma.

Background: The incidence of papillary thyroid carcinoma (PTC) is higher in females than in males, but it remains unclear whether gender is associated with the aggressiveness of this disease. We aimed to clarify the influence of gender on the risk of developing lymph node metastasis (LNM) and on the prognosis of PTC patients. Study Design. Retrospective cohort study. Setting. Academic tertiary care center. Methods: Clinical data of PTC patients who were admitted to the Department of Endocrine and Breast Surgery, the First Affiliated Hospital of Chongqing Medical University, between January 2013 and December 2018 were retrospectively reviewed. The differences in clinical features and outcomes between female and male patients were compared. Univariate and multivariate logistic regression analyses were conducted to assess the impact of gender on LNM. Kaplan-Meier curves were used to estimate recurrence-free survival (RFS). Results: A total of consecutive 2536 patients were enrolled in this study. Males accounted for 25.2% (639 cases) of all patients. Central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) rates were 52.5% (1346/2536) and 22.0% (558/2536), respectively. Male presented with higher LNM rates than female patients (65.7% vs. 51.2%; P < 0.001). Male gender was independently associated with LNM (OR = 1.93, 95% CI: 1.59-2.35; P < 0.001). After full adjustment, male gender still remained significantly associated with CLNM in all subgroups; however, subgroup analyses indicated no significant relationship between gender and LLNM. In addition, after a median follow-up period of 30 months, no significant difference was found in RFS between female and male patients (P=0.15). Conclusions: This observational cohort study revealed that male gender was significantly associated with CLNM; whereas, LLNM was not different between female and male PTC patients in southwestern China. Moreover, currently, there is insufficient evidence to justify that male gender is an independent prognostic factor for recurrence.

Preoperative and pathological predictive factors of central lymph node metastasis in papillary thyroid microcarcinoma.

OBJECTIVE: The aim of this study was to identify clinical and pathological markers of CLNM in persons with clinical lymph node-negative papillary thyroid microcarcinoma(PTMC). MATERIALS AND METHODS: Retrospective data were analyzed from 804 PTMC clinically negative patients who were receiving thyroid surgery in the First Affiliated Hospital at Chongqing Medical University from January 2017 to December 2018. The CLNM-positive and CLNM-negative groups were categorised according to histological evidence of the central lymph node involvement, statistically, risk variables for CLNM were found. RESULTS: 324 (40.3%) individuals were diagnosed with CLNM. Sex (P=0.001), age at diagnosis (P<0.001), tumour size(P=0.029), microcaccificities presence (P=0.003), capsules discontinuity(P=0.002), multi-focality(P=0.001) and (ETE)extrathyroidal extension (P < 0.001) differed substantially from one positive CLNM group to the next. For multivariate analyses, women (odds ratio [OR] = 0.489), age [OR = 0.540] are the independent protective factors for CLNM; micro-cacification presence (OR = 1.511), discontinuity of capsules (OR= 2.056), multifocality(OR=1.486) and ETE(OR=10.613) are the independent risk factors for CLNM. Feature curves of the receiver were built and the AUC is 0.763. 32.1% percent (80 patients) of the 249 patients who did not have any of the four risk variables got CLNM. This contrasted with the incidence of CLNM in this research, which was as high as 49.1%. CONCLUSIONS: CLNM has been connected with female sex, age - within 45 years, microcacification occurrences, capsule discontinuity, multifocality and extrathyroid expansion. The patients may benefit from the surgical decision of pCLND whether there are risk factors combined.

Risk factors and prediction model of level II lymph node metastasis in papillary thyroid carcinoma.

Introduction: Surgical management of lateral lymph nodes in papillary thyroid carcinoma, especially at level II, remains controversial. This study aimed to investigate the risk factors for level II lymph node metastasis in patients with papillary thyroid carcinoma and establish a prediction model to estimate the metastatic risk. Materials and methods: A total of 768 patients with papillary thyroid carcinoma underwent thyroidectomy and central plus lateral lymph node dissection, including levels VI, II, III, and IV, at the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2018. Data on the clinicopathological characteristics were collected and analyzed. Univariate and multivariate analyses were performed to identify risk factors for level II lymph node metastasis. Subsequently, a predictive model was established based on the results of the multivariate analyses. Results: The level II lymph node metastatic rate was 34.11% with the following features: largest tumor diameter >20 mm (Odds ratio=1.629, P=0.026), located in the upper pole (Odds ratio=4.970, P<0.001), clinical lymph node-positive (clinical central lymph node-positive: Odds ratio=1.797; clinical lateral lymph node-positive: Odds ratio=1.805, P=0.008), vascular invasion (Odds ratio=6.759, P=0.012), and rate of central lymph node metastasis (Odds ratio=2.498, P<0.001). Level III lymph node metastasis (Odds ratio=2.749, P<0.001) and level IV lymph node metastasis (Odds ratio=1.732, P=0.007) were independent of level II lymph node metastasis predictors. The prediction model's areas under the receiver operating characteristic curve were 0.815 and 0.804, based on bootstrapping validation. Level II lymph node metastasis was associated with the tumor-free survival rate of patients with papillary thyroid carcinoma (P<0.001). Conclusions: Largest tumor diameter >20 mm, located in the upper pole, clinical lymph node-positive, vascular invasion, rate of central lymph node metastasis, and levels III and IV lymph node metastases were independent level II lymph node metastasis predictors. We developed a prediction model for level II lymph node metastasis. Overall, level II lymph node metastasis dissection should be individualized according to clinicopathological data both preoperatively and intraoperatively.

Physiological of biochar and α-Fe2O3 nanoparticles as amendments of Cd accumulation and toxicity toward muskmelon grown in pots.

BACKGROUND: Due to the severe cadmium (Cd) pollution of farmland soil, effective measures need to be taken to reduce the Cd content in agricultural products. In this study, we added α-Fe2O3 nanoparticles (NPs) and biochar into Cd-contaminated soil to investigate physiological responses of muskmelon in the whole life cycle. RESULTS: The results showed that Cd caused adverse impacts on muskmelon (Cucumis melo) plants. For instance, the chlorophyll of muskmelon leaves in the Cd alone treatment was reduced by 8.07-32.34% in the four periods, relative to the control. The treatments with single amendment, α-Fe2O3 NPs or 1% biochar or 5% biochar, significantly reduced the soil available Cd content, but the co-exposure treatments (α-Fe2O3 NPs and biochar) had no impact on the soil available Cd content. All treatments could reduce the Cd content by 47.64-74.60% and increase the Fe content by 15.15-95.27% in fruits as compared to the Cd alone treatment. The KEGG enrichment results of different genes in different treatments indicated that single treatments could regulate genes related to anthocyanin biosynthesis, glutathione metabolism and MAPK signal transduction pathways to reduce the Cd toxicity. CONCLUSIONS: Overall the combination of biochar and α-Fe2O3 NPs can alleviate Cd toxicity in muskmelon. The present study could provide new insights into Cd remediation in soil using α-Fe2O3 NPs and biochar as amendments.

Risk Factors and a Prediction Model of Lateral Lymph Node Metastasis in CN0 Papillary Thyroid Carcinoma Patients With 1-2 Central Lymph Node Metastases.

Background: Papillary thyroid cancer (PTC) in clinically lymph node-negative (cN0) patients is prone toward lymph node metastasis. As a risk factor for tumor persistence and local recurrence, lateral lymph node metastasis (LLNM) is related to the number of central lymph node metastases (CLNMs). Methods: We performed LLNM risk stratification based on the number of CLNMs for cN0 PTC patients who underwent thyroidectomy and lymph node dissection between January 2013 and December 2018. A retrospective analysis was applied to the 274 collected patients with 1-2 CLNMs. We examined the clinicopathological characteristics of the patients and constructed a LASSO model. Results: In the 1-2 CLNM group, tumors >10 mm located in the upper region and nodular goiters were independent risk factors for LLNM. Specifically, tumors >20 mm and located in the upper region contributed to metastasis risk at level II. Hashimoto's thyroiditis reduced this risk (p = 0.045, OR = 0.280). Age ≤ 30 years and calcification (microcalcification within thyroid nodules) correlated with LLNM. The LASSO model divided the population into low- (25.74%) and high-risk (57.25%) groups for LLNM, with an AUC of 0.715. Conclusions: For patients with 1-2 CLNMs, young age, calcification, nodular goiter, tumor >10 mm, and tumor in the upper region should alert clinicians to considering a higher occult LLNM burden. Close follow-up and therapy adjustment may be warranted for high-risk patients.

Prediction Model of Pathologic Central Lymph Node Negativity in cN0 Papillary Thyroid Carcinoma.

BACKGROUND: Most patients with papillary thyroid carcinoma (PTC) have an excellent prognosis. Although central lymph node invasion is frequent, management via central lymph node dissection (CLND) remains controversial. The present study retrospectively investigated independent predictors of pathologic central lymph node negativity (pCLN-) and established a prediction model for pCLN- in clinical lymph node negativity (cN0) PTC. METHODS: A total of 2,687 patients underwent thyroid surgery for cN0 PTC from 2013 to 2018 at the First Affiliated Hospital of Chongqing Medical University, and lobectomy plus ipsilateral CLND was the basic surgical extent. Clinicopathological characteristics were reviewed and analyzed. Univariate and multivariate analyses were performed to identify factors related to pCLN-. A prediction model was established based on the results of multivariate analyses. RESULTS: The pCLN- rate was 51.5% (1,383/2,687). Multivariate analysis revealed that sex, age, thyroid stimulating hormone (TSH), size, location, laterality, unifocality and extrathyroidal extension negativity (ETE-) were independent predictors of pCLN-. The nomogram showed good discriminative ability (C-index: 0.784 and 0.787 in derivation and validation groups, respectively) and was well calibrated. We quantified the clinical usefulness of the nomogram by decision curve analysis. The median length of follow-up was 30 (range 12- 83) months, and 190 cases were lost, with a follow-up rate of 92.9% (2,497/2,687). Of the 2,687 patients included, 21 (0.8%) experienced recurrence. CONCLUSION: This nomogram, which integrates available preoperative clinicopathological features and intraoperative frozen biopsy outcomes, is a reliable tool with high accuracy to predict pCLN- in cN0 PTC.

Application of Machine Learning Algorithms to Predict Central Lymph Node Metastasis in T1-T2, Non-invasive, and Clinically Node Negative Papillary Thyroid Carcinoma.

Purpose: While there are no clear indications of whether central lymph node dissection is necessary in patients with T1-T2, non-invasive, clinically uninvolved central neck lymph nodes papillary thyroid carcinoma (PTC), this study seeks to develop and validate models for predicting the risk of central lymph node metastasis (CLNM) in these patients based on machine learning algorithms. Methods: This is a retrospective study comprising 1,271 patients with T1-T2 stage, non-invasive, and clinically node negative (cN0) PTC who underwent surgery at the Department of Endocrine and Breast Surgery of The First Affiliated Hospital of Chongqing Medical University from February 1, 2016, to December 31, 2018. We applied six machine learning (ML) algorithms, including Logistic Regression (LR), Gradient Boosting Machine (GBM), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Decision Tree (DT), and Neural Network (NNET), coupled with preoperative clinical characteristics and intraoperative information to develop prediction models for CLNM. Among all the samples, 70% were randomly selected to train the models while the remaining 30% were used for validation. Indices like the area under the receiver operating characteristic (AUROC), sensitivity, specificity, and accuracy were calculated to test the models' performance. Results: The results showed that ~51.3% (652 out of 1,271) of the patients had pN1 disease. In multivariate logistic regression analyses, gender, tumor size and location, multifocality, age, and Delphian lymph node status were all independent predictors of CLNM. In predicting CLNM, six ML algorithms posted AUROC of 0.70-0.75, with the extreme gradient boosting (XGBoost) model standing out, registering 0.75. Thus, we employed the best-performing ML algorithm model and uploaded the results to a self-made online risk calculator to estimate an individual's probability of CLNM (https://jin63.shinyapps.io/ML_CLNM/). Conclusions: With the incorporation of preoperative and intraoperative risk factors, ML algorithms can achieve acceptable prediction of CLNM with Xgboost model performing the best. Our online risk calculator based on ML algorithm may help determine the optimal extent of initial surgical treatment for patients with T1-T2 stage, non-invasive, and clinically node negative PTC.

Comprehensive evaluation of risk factors for lymph node metastasis in patients with papillary thyroid carcinoma.

With the increasing incidence of papillary thyroid cancer (PTC), it is important to risk-stratify patients who may have a more aggressive tumor biology. The present study aimed to evaluate the risk factors for lymph node metastasis (LNM) in patients with PTC, which may provide a significant reference for clinical diagnosis and treatment. In total, 1,045 patients with PTC [313 with PT microcarcinoma (PTMC) and 732 with non-PTMC] between August 2016 and August 2019 were investigated. The B-type Raf kinase (BRAF) V600E mutation was tested in all samples. The clinical data (sex, age, tumor location, sample type and pathological features) were retrospectively analyzed. Logistic regression analysis was performed to evaluate independent risk factors for LNM. A total of 181/313 (57.8%) PTMC cases and 145/732 (19.8%) non-PTMC cases had a BRAF V600E mutation. In the PTMC cases, significant differences in sex and sample type were identified (BRAF V600E mutation vs. wild-type). In the non-PTMC cases, significant differences in sex and age were identified (BRAF V600E mutation vs. wild-type). Female sex and tumor diameter ≤1 cm were significant independent predictors of LNM in PTC. In PTMC, female sex was a significant independent predictor of LNM. A bilateral tumor was an independent protective factor for LNM in PTC, PTMC and non-PTMC. The BRAF V600E mutation rate of ultrasound-guided fine-needle aspiration cytology was higher compared with FFPE in PTMC (P=0.018). In contrast to previous studies, the results of the present study suggested that being female and having a tumor of diameter ≤1 cm were risk factors for LNM, and that the BRAF wild-type of PTMC may be more aggressive than other types. Notably, the position of the tumor in the bilateral thyroid was also an independent protective factor for LNM. Therefore, ultrasound-guided fine-needle aspiration should be recommended for gene analysis (BRAF V600E) in PTMC. In addition, clinicians should consider an individualized treatment according to gene mutations, sex, age, tumor size and the location of the tumor, in order to achieve an improved therapeutic efficacy.

Clinical implications of Delphian lymph node metastasis in papillary thyroid carcinoma.

BACKGROUND: As is known, identifying risk factors precisely for lymph node metastasis (LNM) plays a vital role in initial treatment for papillary thyroid carcinoma (PTC). Nonetheless, whether Delphian lymph node (DLN) metastasis has value in predicting LNM remains an open question. This study covered a sample of 1,575 patients, which is the largest sample group so far, aiming to assess the predictive validity of DLN metastasis in PTC. METHODS: This retrospective cohort study was conducted with 1,575 eligible PTC patients who underwent thyroid operation between July 2013 and December 2018 and clinicopathologic parameters of patients with DLN metastasis were compared with those without DLN metastasis. RESULTS: The incidence of DLN metastasis, according to our research samples, is 24.4% (384/1,575 patients). And results show that DLN positivity was closely associated with adverse prognostic factors including younger age, larger tumor size, extrathyroid extension, tumor location in the isthmus or upper lobe of the thyroid, number of LNM >5, higher recurrence. After carefully adjusting important confounding factors, we find that in multivariate logistic regression analyses, DLN metastasis is an independent predictor for both central LNM (CLNM, adjusted OR =7.81, P<0.001) and lateral LNM (LLNM, adjusted OR =3.40, P<0.001). Moreover, the stratified analyses also show convincing evidence of a positive correlation between DLN metastasis and LNM in levels II-IV in the vast majority of subgroups. CONCLUSIONS: The present study suggests that DLN metastasis is an independent risk factor for CLNM and LLNM of levels II-IV. The cervical lymph nodes should be meticulously evaluated to guide tailored treatment during operation in patients with DLN involvement.

Multi-gene assay and clinical characteristics research in papillary thyroid carcinoma.

BACKGROUND: To investigate the significance of multi-gene assay in papillary thyroid carcinoma (PTC) patients in clinical practice. METHODS: From April to December 2019, medical records of 68 patients with PTC after the initial surgery were retrospectively collected and analyzed in terms of the relations between gene mutations and clinicopathological characteristics. RESULTS: RET/PTC rearrangement was not detected in BRAF V600E mutation patients (P<0.001). Besides, compared with wild-type patients, BRAF V600E mutation was associated with significantly older age (P=0.001) and a higher rate of extrathyroid invasion (P=0.023). Significantly higher BRAF V600E mutation rates were found in clinical lymph node-negative (P=0.041) and non-metastatic lateral lymph nodes (P=0.027) patients as RET/PTC rearrangement was associated with younger age (P=0.001) and the increasing metastatic number of lymph nodes (P=0.020). Compared to other gene mutations, the multivariate analysis showed that larger tumor size [odds ratio (OR), 8.831; 95% CI: 1.971-35.578; P=0.004], the BRAF V600E mutation alone(OR, 10.567; 95% CI: 1.748-63.873; P=0.010) or in combination with one additional gene mutation (OR, 8.654; 95% CI: 1.453-68.603; P=0.041), and Hashimoto's thyroiditis (OR, 0.112; 95% CI: 0.025-0.499; P=0.004) were all independent predictors for the prevalence of ETE. CONCLUSIONS: BRAF V600E mutation was associated with older age and the aggressiveness of PTC but was independent of lymph node metastasis (LNM). RET/PTC rearrangement suggested more LNM in young patients with PTC. BRAF V600E mutation combined with other gene mutations, namely, multi-gene mutations, could indicate a higher aggressiveness in PTC.

PTC located in the upper pole is more prone to lateral lymph node metastasis and skip metastasis.

BACKGROUND: Lateral lymph node metastasis (LLNM) is very common in papillary thyroid carcinoma (PTC). The influence of tumour location on LLNM remains controversial. The purpose of this study was to reveal the association between PTC tumours located in the upper pole and LLNM. METHODS: We reviewed a total of 1773 PTC patients who underwent total thyroidectomy with central and lateral lymph node dissection between 2013 and 2018. Patients were divided into two groups according to tumour location. Univariate and multivariate analyses were performed to identify risk factors associated with LLNM and "skip metastasis". RESULTS: In the upper pole group, LLNM and skip metastasis were significantly likely to occur. Multivariate analysis showed that tumours located in the upper pole, male sex, extrathyroidal extension (ETE), central lymph node metastasis (CLNM) and tumour size were independent risk factors for LLNM, with odds ratios ([ORs], 95% confidence intervals [CIs]) of 2.136 (1.707-2.672), 1.486 (1.184-1.867), 1.332 (1.031-1.72), 4.172 (3.279-5.308) and 2.496 (1.844-3.380), respectively. Skip metastasis was significantly associated with the primary tumour location in the upper pole and age > 55 years, with ORs of 4.295 (2.885-6.395) and 2.354 (1.522-3.640), respectively. CONCLUSIONS: In our opinion, papillary thyroid tumours located in the upper pole may have an exclusive drainage pathway to the lateral lymph nodes. When the tumour is located in the upper pole, lateral neck dissection should be evaluated meticulously.

Development and validation of web-based nomograms for predicting lateral lymph node metastasis in patients with papillary thyroid carcinoma.

BACKGROUND: The purpose of this study was to evaluate the factors associated with lateral lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC), and to develop two web-based nomograms that predict the probability of level-II and level-III/IV LLNM in these patients. METHODS: The records of 653 patients with PTC were retrospectively reviewed. Univariate and multivariate analyses were performed to identify risk factors associated with LLNM in 460 patients ("derivation group"). Two models [including and excluding the subregions of central lymph node metastasis (CLNM)] were used to predict the probability of level-II LLNM; the same two models were also used for level-III/IV LLNM. Model performance was assessed using receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) in 193 patients ("validation group"). Two web-based nomograms were established. RESULTS: Increased tumor size, a tumor in the upper lobe, and prelaryngeal and ipsilateral paratracheal lymph node metastasis (LNM) were significantly associated with level-II LNM (P<0.05). Increased tumor size, a tumor in the upper lobe, and certain subregions of CLNM were associated with level-III/IV LNM (P<0.05). Use of ROC analysis of each model indicated that including subgroups of CLNM led to better model performance than excluding these subgroups. We quantified the benefit of each model by using DCA analysis in the validation group. CONCLUSIONS: Our web-based nomograms provide quantification of risk for LLNM in patients with PTC before and during surgery.

Identification of Genes with Prognostic Value in the Breast Cancer Microenvironment Using Bioinformatics Analysis.

BACKGROUND Stromal and immune cells play essential roles in the development of breast cancer (BC). This study was conducted to identify prognosis-related genes from the tumor microenvironment. MATERIAL AND METHODS The gene expression profiles of 622 BC samples were downloaded from TCGA (The Cancer Genome Atlas) database. Stromal and immune scores were calculated by using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumours using Expression data) algorithm. Then, differentially expressed genes (DEGs) between the high score group and the low score group were screened. The intersecting DEGs were selected through Venn diagrams, and survival analysis was conducted. Functional and pathway enrichment analyses were performed using the DAVID (Database for Annotation, Visualization and Integrated Discovery), and a protein-protein interaction (PPI) network was constructed with the STRING database and Cytoscape. These genes were validated for prognostic value by use of the KM (Kaplan-Meier) plotter tool. RESULTS The low immune score group was associated with a poor prognosis. However, there was no difference in the prognosis between the high and low stromal score groups. A total of 248 intersecting DEGs were found in BC, and 61 genes were significantly associated with the prognosis of BC patients in the TCGA database. These genes were enriched in the immune response, components of the plasma membrane, and receptor activity. Furthermore, in the validation group, 31 of 61 genes were significantly associated with prognosis. CONCLUSIONS Our bioinformatics analysis identified 31 tumor microenvironment-related genes as potential prognostic predictors for breast cancer patients. Some of these genes that have not been widely investigated previously, such as CXCL9, GPR18, S1PR4, SASH3, and PYH1N1, might be additional predictive factors for BC patients.

The Recovery of Thyroid Function in Low-Risk Papillary Thyroid Cancer After Lobectomy: A 3-Year Follow-Up Study.

Purpose: Management strategies after lobectomy for low-risk papillary thyroid carcinoma (PTC) are controversial. This study aimed to identify the proportion of patients among low-risk PTC patients who do not require hormone replacement therapy and to evaluate the risk factors for postoperative hypothyroidism after lobectomy. Patients and Methods: The records of 190 PTC patients who underwent thyroid lobectomy from January 2017 to December 2018 were retrospectively reviewed. Clinicopathological characteristics and follow-up data were collected. Univariate and multivariate analyses were performed to identify the risk factors associated with postoperative hypothyroidism and the recovery of thyroid function. Results: In summary, 74.21% of patients (141/190) had normal thyroid function without levothyroxine supplementation, while 40.53% (77/190) developed temporary or permanent hypothyroidism. Multivariate analysis indicated that higher preoperative thyroid-stimulating hormone (TSH) levels (>2.62 mIU/L), Hashimoto's thyroiditis (HT), and right lobectomy were associated with hypothyroidism (all P<0.05). The Area Under Curve (AUC) by logistic analysis was 0.829. Twenty-eight (28/77, 36.4%) patients recovered to the euthyroid state in the first year after surgery, and this recovery was significantly associated with preoperative TSH level. Forty-nine (49/77, 63.6%) patients developed persistent hypothyroidism. The thyroid function of most patients (11/28, 39.3%) recovered in the third month after surgery. Conclusion: Patients with a lower level of preoperative TSH, with left lobectomy and without Hashimoto's thyroiditis had a higher chance of normal thyroid function within the first year after lobectomy. The recovery of thyroid function was associated with the level of preoperative TSH.

Risk Factors for and Prediction Model of Skip Metastasis to Lateral Lymph Nodes in Papillary Thyroid Carcinoma.

BACKGROUND: Cervical lymph node metastasis is a prognostic factor of papillary thyroid carcinoma (PTC). Skip metastasis (central lymph node negative and lateral lymph node positive) of PTC is not uncommon. This study aimed to retrospectively investigate the risk factors for skip metastasis in PTC and develop a prediction model for skip metastasis. METHODS: A total of 745 PTC patients underwent total thyroidectomy and central plus lateral lymph node dissection at the First Affiliated Hospital of Chongqing Medical University from January 2012 to December 2017. Clinicopathological characteristics were collected and analyzed. Univariate and multivariate analyses were performed to detect the risk factors for skip metastasis. A prediction model was established based on the results of multivariate analyses. RESULTS: The skip metastasis rate was 9.7% (72/745). Age > 55 years (OR 2.63, 95% CI 1.34-5.04, p = 0.004), tumor located in the upper portion (OR 4.15, 95% CI 2.30-7.63, p = 0.001), and unilaterality (OR 2.76, 95% CI 1.14-8.23, p = 0.040) were independent risk factors for skip metastasis. Clinically lymph node-negative (cN0) patients with tumor in the upper portion (24.6%, 43/175) had higher possibility of skip metastasis than those of clinically lateral lymph node-positive (cN1b) patients (5.9%, 10/169) (p = 0.001). The area under the receiver operating characteristic curve of prediction model was 0.734 and 0.740 in derivation group and validation group, respectively. However, skip metastasis was not associated with tumor-free survival rate of PTC patients (p = 0.274). CONCLUSION: Age > 55 years, tumor located in the upper portion, and unilaterality may increase the risk of skip metastasis. We developed the first prediction model for skip metastasis based on clinicopathological parameters in PTC patients.