Predictive Value of Jugulo-omohyoid Lymph Nodes in Lateral Lymph Node Metastasis of Papillary Thyroid Cancer.

BACKGROUND: Jugulo-omohyoid lymph nodes (JOHLN) metastasis has proven to be associated with lateral lymph node metastasis (LLNM). This study aimed to reveal the clinical features and evaluate the predictive value of JOHLN in PTC to guide the extent of surgery. METHODS: A total of 550 patients pathologically diagnosed with PTC between October 2015 and January 2020, all of whom underwent thyroidectomy and lateral lymph node dissection, were included in this study. RESULTS: Thyroiditis, tumor location, tumor size, extra-thyroidal extension, extra-nodal extension, central lymph node metastasis (CLNM), and LLMM were associated with JOHLN. Male, upper lobe tumor, multifocality, extra-nodal extension, CLNM, and JOHLN metastasis were independent risk factors from LLNM. A nomogram based on predictors performed well. Nerve invasion contributed the most to the prediction model, followed by JOHLN metastasis. The area under the curve (AUC) was 0.855, and the p-value of the Hosmer-Lemeshow goodness of fit test was 0.18. Decision curve analysis showed that the nomogram was clinically helpful. CONCLUSION: JOLHN metastasis could be a clinically sensitive predictor of further LLM. A high-performance nomogram was established, which can provide an individual risk assessment of LNM and guide treatment decisions for patients.

Distinct risk factors of lateral lymph node metastasis in patients with papillary thyroid cancer based on age stratification.

INTRODUCTION: Studies have revealed that age is associated with the risk of lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC). This study aimed to identify the optimal cut point of age for a more precise prediction model of LLNM and to reveal differences in risk factors between patients of distinct age stages. METHODS: A total of 499 patients who had undergone thyroidectomy and lateral neck dissection (LND) for PTC were enrolled. The locally weighted scatterplot smoothing (LOWESS) curve and the 'changepoint' package were used to identify the optimal age cut point using R. Multivariate logistic regression analysis was performed to identify independent risk factors of LLNM in each group divided by age. RESULTS: Younger patients were more likely to have LLNM, and the optimal cut points of age to stratify the risk of LLNM were 30 and 45 years old. Central lymph node metastasis (CLNM) was a prominent risk factor for further LNM in all patients. Apart from CLNM, sex(p = 0.033), tumor size(p = 0.027), and tumor location(p = 0.020) were independent predictors for patients younger than 30 years old; tumor location(p = 0.013), extra-thyroidal extension(p < 0.001), and extra-nodal extension(p = 0.042) were independent risk factors for patients older than 45 years old. CONCLUSIONS: Our study could be interpreted as an implication for a change in surgical management. LND should be more actively performed when CLNM is confirmed; for younger patients with tumors in the upper lobe and older patients with extra-thyroidal extension tumors, more aggressive detection of the lateral neck might be considered.

The minimal number of examined lymph nodes for accurate nodal staging and favorable prognosis in T1-2 supraglottic laryngeal squamous cell carcinoma.

OBJECTIVE: The study aimed to investigate the minimal number of examined lymph nodes (ELNs) for accurate assessment of lymph node status and favorable prognosis in patients with stage T1-2 supraglottic laryngeal squamous cell carcinoma (LSCC) who received radical resection. METHODS: Patients with stage T1-2 supraglottic LSCC from the Surveillance, Epidemiology, and End Results (SEER) database and the Chinese Academy of Medical Sciences, Cancer Hospital/National Cancer Center (NCC) were reviewed. The association of the ELN count with the identification of nodal metastasis and overall survival (OS) was analyzed using a multivariate regression model. Locally weighted scatterplot smoothing fitting curve and the 'changepoint' package were adopted to identify the optimal cut points using R. RESULTS: A total of 429 patients from the SEER database and 53 patients from NCC were enrolled. The probability of identifying nodal metastasis was positively related to the ELN count. For patients diagnosed with pathological stage N0 (pN0) disease, the mortality risks rapidly decreased when the amount of ELNs exceeded ten, and those with ELNs >10 had better OS. CONCLUSION: An adequate amount of ELNs benefits precise nodal staging in patients with stage T1-2 supraglottic LSCC. Ten lymph nodes are the minimum number of ELNs. For pN0 patients, an ELN count ≤10 is an unfavorable prognostic factor.

The Optimal Age Threshold for Stratifying the Risks of Disease Progression in Patients with Highly Suspicious Sub-centimeter Thyroid Nodules.

PURPOSE: The study aimed to identify the value and optimal age cutoff to predict the progression of highly suspicious thyroid nodules ≤ 10 mm during active surveillance (AS), and to reveal distinct risk factors in patients of different ages. METHODS: A total of 779 patients with highly suspicious thyroid nodules were enrolled and followed up by ultrasonography. Locally weighted scatterplot smoothing (LOWESS) and the package 'changepoint' were used to identify the optimal age cutoffs using R. Multivariate Cox regression was performed to identify independent prognostic factors in each patient group divided according to age. RESULTS: Age was an independent predictor of nodule progression (P = 0.038). The optimal age cutoff to stratify the risk of nodule progression was 30 years. Younger patients were more likely to have progression of nodules during AS (P < 0.001), including enlargement of nodule size (P = 0.011) and new lesion occurrence (P < 0.001). Nodule size was identified as a risk factor for disease progression in patients younger than 30 years old (P = 0.008, OR 7.946, 95% CI 1.715-36.820), while multifocality (P = 0.018, OR 2.315, 95% CI 1.155-4.639) and thyroiditis (P = 0.028, OR 2.265, 95% CI 1.092-4.699) were independent predictors in patients over 30 years old. CONCLUSIONS: Highly suspicious thyroid nodules ≤ 10 mm in young patients tended to be more progressive. The predictors of disease progression were distinct in patients of different ages.

The optimal number of examined lymph nodes for accurate nodal staging and favorable prognosis of oral tongue squamous cell carcinoma.

OBJECTIVE: The study aimed to determine the optimal count of examined lymph nodes (ELN) for accurate assessment of lymph node status and favorable long-term survival in patients with oral tongue squamous cell carcinoma (OTSCC) who received radical resection. METHODS: Patients with OTSCC who received radical resection between 2004 and 2015 were enrolled from the Surveillance, Epidemiology, and End Results database (SEER) and were randomly divided into two cohorts. The association of ELN count with nodal migration and overall survival (OS) was analyzed using a multivariate regression model with the adjustment of relevant factors. Locally weighted scatterplot smoothing (LOWESS) and 'strucchange' package were adopted to identify the optimal cut points using R. RESULTS: A total of 2077 patients were included in this study. The optimal cut points of ELN count for accurate nodal staging and favorable OS were 19 and 15, respectively. The probability of detecting positive lymph nodes (PLN) significantly increased in patients with ELN count ≥ 19 in comparison to those with ELN count < 19 (training set, P < 0.001; validation set, P = 0.012). A better postoperative prognosis was observed in patients with ELN count ≥ 15 than those with fewer ELN (training set, P = 0.001, OR: 0.765; validation set, P = 0.016, OR: 0.678). CONCLUSION: The optimal cut point of ELN count to ensure the accuracy of nodal staging and to achieve a favorable postoperative prognosis were 19 and 15, respectively. The ELN count beyond the cutoff values might improve the accuracy of cancer staging and OS.

Re-Dispersion of Platinum From CNTs Substrate to α-MoC1 - x to Boost the Hydrogen Evolution Reaction.

Developing high-performance electrocatalysts toward hydrogen evolution reaction (HER) is important for clean and sustainable hydrogen energy, yet still challenging. Herein, an α-MoC1 - x induced redispersing strategy to construct a superior HER electrocatalyst (Pt/CNTs-N + α-MoC1 - x ) by mechanical mixing of α-MoC1 - x with Pt/CNTs-N followed by thermal reduction is reported. It is found that thermo-activation treatment enables partial Pt atoms to redisperse on α-MoC1 - x substrate from carbon nanotubes, which creates dual active interfaces of Pt species dispersed over carbon nanotubes and α-MoC1 - x . Benefiting from the strong electronic interaction between the Pt atom and α-MoC1 - x , the utilization efficiency of the Pt atom and the zero-valence state of Pt is evidently enhanced. Consequently, Pt/CNTs-N + α-MoC1 - x catalyst exhibits excellent HER activity with low overpotentials of 17 and 34 mV to achieve a current density of 10 mA cm-2 in acidic and alkaline electrolytes, respectively. Density functional theory calculations further reveal that the synergistic effect between Pt and α-MoC1 - x makes it accessible for the dissociation of water molecules and subsequent desorption of hydrogen atoms. This work reveals the crucial roles of α-MoC1 - x additives, providing practical solutions to enhance platinum dispersion, and thereby enhance the catalytic activity in HER.

Survival and long-term quality-of-life of concurrent chemoradiotherapy versus surgery followed by radiotherapy with or without concurrent chemotherapy for the treatment of resectable stage III/IV hypopharyngeal carcinoma.

OBJECTIVE: We evaluated the utility of concurrent chemoradiotherapy (CCRT) compared to surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) (SRT) in terms of improving the life expectancy and quality-of-life (QOL) of patients with stage III/IV hypopharyngeal squamous cell carcinomas (HPSCCs). METHODS: From January 2010 to July 2018, a total of 299 patients with stage III/IV HPSCC who received surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) (SRT, n = 111), or concurrent chemoradiotherapy (CCRT, n = 188) in our hospital were included. We measured overall survival (OS) and disease-free survival (DFS). We used the EORTC QLQ-C30, QLQ-H&N35, and Voice handicap index-30 (VHI-30) instruments to assess the long-term QOL. RESULTS: The OS and DFS afforded by SRT were significantly better than those associated with CCRT (p = 0.039; p = 0.048 respectively), especially for stage N2-N3 patients. CCRT patients experienced better speech outcomes. CONCLUSION: For resectable stage III/IV HPSCC patients, appropriate treatment plans should be selected comprehensively considering survival rate, QOL, patient preference and multidisciplinary treatment.

Evaluation of serum B7-H3 expression, ultrasound and clinical characteristics to predict the risk of cervical lymph node metastases in papillary thyroid carcinoma by nomogram.

BACKGROUND: Improving the preoperative diagnosis of cervical lymph node metastasis (LNM) will help improve the clinical outcomes of papillary thyroid carcinoma (PTC) patients. B7-H3, as an immune checkpoint of the B7 family, is highly expressed in PTC tissues and related to LNM and prognosis. We aimed to explore the clinical values of serum B7-H3 (sB7-H3) in predicting LNM in PTC by a nomogram prediction model. METHODS: From September 2019 to May 2021, a total of 344 PTC patients with primary surgery in our hospital were enrolled in this research. Enzyme-linked Immunosorbent Assay (ELISA) was used to detect sB7-H3 from the peripheral blood of PTC patients and normal controls. We created a nomogram prediction model in combination with sB7-H3 expression, clinical and ultrasound characteristics to predict LNM in the early stage. RESULTS: Gender (p = 0.001), age (p = 0.015), tumor size (p < 0.001), number of tumors (p = 0.021) and sB7-H3 expression (p = 0.003) were independent risk factors for LNM in PTC. All the factors were included in the nomogram. The area under the curve (AUC) was 73.9% (95% CI, 68.12%-79.69%). CONCLUSION: The nomogram is helpful in assessing the risk of LNM in PTC. sB7-H3 has excellent potential in predicting LNM in patients with PTC as an adjunctive ultrasound tool.

Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma.

Background: B7-H3, also known as CD276, an important immune checkpoint member of the B7-CD28 family, is confirmed as a promising target after PD-L1 in clinical trials. Although the overexpression of B7-H3 has been associated with invasive metastatic potential and poor prognosis in multiple types of cancer, nothing is known regarding the expression profiles of B7-H3 in papillary thyroid carcinoma (PTC). In this study, we carried out a large-scale analysis of B7-H3 expression in PTC patients and evaluated the potential clinical significance of B7-H3. Methods: In total, data from 1,210 samples, including 867 cases from TCGA and four GEO datasets, were collected for B7-H3-related transcriptome analyses, and 343 postoperative, whole-tumor sections were collected from patients with PTC at our institute for B7-H3-specific immunohistochemistry (IHC) staining. The statistical analysis was primarily accomplished using the R project for statistical computing. Results: B7-H3 positivity was found in 84.8% of PTC patients (291/343), and the mRNA and protein expression levels of B7-H3 in PTC were markedly higher than those of para-tumor tissues (p < 0.001), demonstrating that B7-H3 can serve as a potential diagnostic biomarker for PTC. The significant upregulation of B7-H3 in PTC is caused by distinct patterns of CNVs and CpG DNA methylation. Functional enrichment analysis confirmed that high B7-H3 expression was significantly associated with specific immune features and angiogenesis. High B7-H3 protein expression was associated with tumor size (p = 0.022), extrathyroidal extension (ETE) (p = 0.003), and lymph node metastasis (LNM) (p < 0.001). More importantly, multivariate analysis confirmed that B7-H3 was an independent predictor of relapse-free survival (RFS) (p < 0.05). In the subgroup analysis, positive B7-H3 staining was associated with worse RFS in patients with primary tumor size ≥2 cm (p < 0.05), age ≥55 years (p < 0.05), LNM (p = 0.07), multifocality (p < 0.05), and ETE (p < 0.05). In addition, Circos plots indicated that B7-H3 was significantly associated with other immune checkpoints in the B7-CD28 family. Conclusion: This is the first comprehensive study to elucidate the expression profile of B7-H3 in PTC. Our observations revealed that B7-H3 is a novel independent biomarker for predicting LNM and disease recurrence for PTC patients, and it thus may serve as an indicator that could be used to improve risk-adapted therapeutic strategies and a novel target for immunotherapy strategies for patients who undergo an aggressive disease course.

Engineering the Local Coordination Environment and Density of FeN4 Sites by Mn Cooperation for Electrocatalytic Oxygen Reduction.

Single atom sites (SAS) of FeN4 are clarified as one of the most active components for the oxygen reduction reaction (ORR). Effective strategies by engineering the local coordination environment and site density of FeN4 sites are crucial to further enhance the electrocatalytic ORR performance. Herein, the integration of a second metal of Mn with Fe to construct Fe&Mn/N-C catalysts with enhanced density of FeN4 active sites and modulated electronic structure is reported. The formation of MnN4 centers modulates the local environment of FeN4 sites and reserves more FeN4 embedded in carbon substrate by forming the possible FeN4 -O-MnN4 configurations. Density functional theory calculations demonstrate that the overall energy barrier of ORR is decreased over the FeN4 -O-MnN4 moieties. Therefore, the Fe&Mn/N-C catalyst exhibits enhanced ORR performance both in alkaline and acidic solution (half-wave potentials are 0.904 and 0.781 V). This work provides an effective strategy by modulating the local electronic structure and density of FeN4 active sites to improve the ORR activity and stability through Mn cooperation.