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.

Comprehensive analysis of single-cell and bulk RNA-sequencing data identifies B cell marker genes signature that predicts prognosis and analysis of immune checkpoints expression in head and neck squamous cell carcinoma.

Recent studies have shown that B cells and the associated tertiary lymphoid structures (TLS) correlate with the response of patients to immune checkpoint inhibitors (ICIs) and predict overall survival (OS) in cancer patients. We screened 145 B cell marker genes (BCMG) by a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of head and neck squamous cell carcinoma (HNSC) from the Gene Expression Omnibus (GEO) database. The BCMG signature (BCMGS) was established using The Cancer Genome Atlas (TCGA) dataset of HNSC and verified in four independent datasets. The multivariate Cox regression analysis identified the signature as an independent prognostic factor. A prognostic nomogram was constructed with independent prognostic factors using the TCGA dataset. GO and KEGG analysis revealed the underlying signaling pathways related to this signature. Study of immune profiles showed that patients in the low-risk group presented discriminative immune-cell infiltrations. Furthermore, the low-risk group was featured by higher TCR and BCR diversity, which suggested that low-risk patients may be more sensitive to ICIs. Immunohistochemistry was performed, and we found that high expression of FTH1 was significantly correlated with poor OS (P = 0.025). The expression of TIM-3, LAG-3 and PD-1 was positively correlated and associated with better OS in HNSC. However, there was no statistically significant difference between PD-L1, PD-L2, CTLA-4, TIGIT and prognosis. The BCMGS was a promising prognostic biomarker in HNSC, which may help to interpret the responses to immunotherapy and provide a new perspective for future research on the treatment in HNSC.

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.

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.

Twist-Net: A multi-modality transfer learning network with the hybrid bilateral encoder for hypopharyngeal cancer segmentation.

Hypopharyngeal cancer (HPC) is a rare disease. Therefore, it is a challenge to automatically segment HPC tumors and metastatic lymph nodes (HPC risk areas) from medical images with the small-scale dataset. Combining low-level details and high-level semantics from feature maps in different scales can improve the accuracy of segmentation. Herein, we propose a Multi-Modality Transfer Learning Network with Hybrid Bilateral Encoder (Twist-Net) for Hypopharyngeal Cancer Segmentation. Specifically, we propose a Bilateral Transition (BT) block and a Bilateral Gather (BG) block to twist (fuse) high-level semantic feature maps and low-level detailed feature maps. We design a block with multi-receptive field extraction capabilities, M Block, to capture multi-scale information. To avoid overfitting caused by the small scale of the dataset, we propose a transfer learning method that can transfer priors experience from large computer vision datasets to multi-modality medical imaging datasets. Compared with other methods, our method outperforms other methods on HPC dataset, achieving the highest Dice of 82.98%. Our method is also superior to other methods on two public medical segmentation datasets, i.e., the CHASE_DB1 dataset and BraTS2018 dataset. On these two datasets, the Dice of our method is 79.83% and 84.87%, respectively. The code is available at: https://github.com/zhongqiu1245/TwistNet.

CCS-Net: Cascade Detection Network With the Convolution Kernel Switch Block and Statistics Optimal Anchors Block in Hypopharyngeal Cancer MRI.

Magnetic resonance imaging (MRI) is a common diagnostic method for hypopharyngeal cancer (HPC). It is a challenge to automatically detect HPC tumors and swollen lymph nodes (HPC risk areas) from MRI slices because of the small size and irregular shape of HPC risk areas. Herein, we propose a cascade detection network with Convolution Kernel Switch (CKS) Block and Statistics Optimal Anchors (SOA) Block in HPC MRI (CCS-Net). CKS Block can adaptively switch standard convolution to deformable convolution in some appropriate layers to detect irregular objects more efficiently without taking up too much computing resources. SOA Block can automatically generate the optimal anchors based on the size distribution of objects. Compared with other methods, our method achieves splendid detection performance and outperforms other methods on the HPC dataset (more than 1800 T2 MRI slices), achieving the highest AP50 of 78.90%. Experiments show that the proposed network can be the basis of a computer aided diagnosis utility that helps achieve faster and more accurate diagnostic decisions for HPC.

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.

Expression of recombinant human Apolipoprotein A-IMilano in Nicotiana tabacum.

Apolipoprotein A-IMilano (Apo A-IMilano) is a natural mutant of Apolipoprotein. It is currently the only protein that can clear arterial wall thrombus deposits and promptly alleviate acute myocardial ischemia. Apo A-IMilano is considered as the most promising therapeutic protein for treating atherosclerotic diseases without obvious toxic or side effects. However, the current biopharmaceutical platforms are not efficient for developing Apo A-IMilano. The objectives of this research were to express Apo A-IMilano using the genetic transformation ability of N. tabacum. The method is to clone the coding sequence of Apo A-IMilano into the plant binary expression vector pCHF3 with a Flag/His6/GFP tag. The constructed plasmid was transformed into N. tabacum by a modified agrobacterium-mediated method, and transformants were selected under antibiotic stress. PCR, RT-qPCR, western blot and co-localization analysis was used to further verify the resistant N. tabacum. The stable expression and transient expression of N. tabacum were established, and the pure product of Apo A-IMilano was obtained through protein A/G agarose. The results showed that Apo A-IMilano was expressed in N. tabacum with a yield of 0.05 mg/g leaf weight and the purity was 90.58% ± 1.65. The obtained Apo A-IMilano protein was subjected to amino acid sequencing. Compared with the theoretical sequence of Apo A-IMilano, the amino acid coverage was 86%, it is also found that Cysteine replaces Arginine at position 173, which indicates that Apo A-IMilano, a mutant of Apo A-I, is accurately expressed in N. tabacum. The purified Apo A-IMilano protein had a lipid binding activity. The established genetic modification N. tabacum will provide a cost-effective system for the production of Apo A-IMilano. Regarding the rapid propagation of N. tabacum, this system provides the possibility of large-scale production and accelerated clinical translation of Apo A-IMilano.

Complications and oncological outcomes after salvage surgery for recurrent and residual hypopharyngeal squamous cell carcinoma: a retrospective cohort study.

Background: Salvage surgery for hypopharyngeal squamous cell carcinoma (HPSCC) after radiotherapy may result in several postoperative complications and the oncological outcome is unsatisfying. Therefore, identifying the risk factors for postoperative complications and oncological outcome after salvage surgery is important. This study aimed to determine which HPSCC patients might benefit from salvage surgery following previous radiotherapy. Methods: We retrospectively analyzed 91 HPSCC patients who underwent salvage surgery due to locoregional recurrence/residual disease after radiotherapy. The pre- and intraoperative characteristics with complications and oncological outcomes were collected through medical records and telephone follow-up. Risk factors for complications were analyzed by binary logistic regression. The oncological outcomes were assessed by overall survival (OS) after salvage surgery. Kaplan-Meier curves and Cox proportional hazard regression analysis were used for univariate and multivariate survival analyses. Results: Postoperative complications occurred in 40.7% of patients, with pharyngo-cutaneous fistula (PCF) occurring in 29.7% of patients. Salvage surgery for local disease was the only independent risk factor for postoperative complications and PCF [complications: odds ratio (OR) =5.298, 95% confidence interval (CI): 1.163-24.130, P=0.031; PCF: OR =4.543, 95% CI: 1.187-17.387, P=0.027). In the subgroup of patients with local disease, time of curative treatment initiation >90 days (OR =7.331, 95% CI: 1.278-42.054, P=0.025) and preoperative hemoglobin <118 g/L (OR =10.101, 95% CI: 1.026-99.492, P=0.045) were independent risk factors for postoperative complications, while free flap reconstruction was an independent protective factor for PCF (OR =0.099, 95% CI: 0.010-0.934, P=0.043). The median OS time was 17 months, with 5-year OS rates of 30%. Age at salvage surgery <50 years [hazard ratio (HR) =2.047, 95% CI: 1.217-3.443, P=0.007] and recurrence or retreatment clinical T stage 3-4 (rcT3-4) (HR =2.051, 95% CI: 1.219-3.450, P=0.007) were identified as risk factors for OS. The 5-year OS rates of patients without and with both risk factors were 43% and 10% (P=0.001). Conclusions: Salvage surgery for locoregional recurrence/residual disease after previous radiotherapy could improve survival in selected patients with HPSCC. Patients with local recurrence/residual disease had a higher complication rate. Efforts can be made to shorten the time of curative treatment initiation and treat anemia to reduce the risk of postoperative complications in this subgroup.

The clinicopathological significance of PD-L1 expression assessed by the combined positive score (CPS) in head and neck squamous cell carcinoma.

The expression of programmed cell death-ligand 1 (PD-L1) is being used as a predictive biomarker for immunotherapy in head and neck squamous cell carcinoma (HNSCC). Our study was a retrospective cohort that assessed PD-L1 expression levels through immunohistochemistry (IHC) in 119 surgical specimens from HNSCC patients. The expression of PD-L1 was evaluated by IHC staining using the monoclonal antibody 22C3 (Dako) and the combined positive score (CPS). The relationship between the PD-L1 expression and clinicopathologic features was analyzed. 107 cases (89.9%) and 52 cases (43.7%) were positive for PD-L1 expression when the CPS cutoff value was set at 1 and 20 respectively. The tumor stage (P = 0.022) and tumor site (P = 0.004) were significantly correlated with the PD-L1 expression (CPS ≥ 1). Non-diabetic patients (P = 0.046) were corelated to positive PD-L1 expression (CPS ≥ 20). When evaluating PD-L1 expression in 40 laryngeal squamous cell carcinomas (LSC), the nodal stage was found to be significantly associated with high expression of PD-L1 (CPS ≥ 20) (P = 0.042). As for 36 patients with hypopharyngeal squamous cell carcinomas (HPSC), the positive PD-L1 expression (CPS ≥ 1) were typically younger (P = 0.030) and patients without type II diabetes (P = 0.040). We evaluated all possible clinical prognostic factors in the univariate Cox model, and there was no significant correlation between clinical characteristics and survival. The results of our findings may help to understand the association between the PD-L1 expression and clinicopathological characteristics, and it showed no significant correlation between the expression of PD-L1 and OS in HNSCC.

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.

Acceptance of disability, coping style, perceived social support and quality of life among patients with chronic lymphedema: a cross-sectional study.

OBJECTIVE: To examine acceptance of disability, coping style, perceived social support, and quality of life and to explore the relationships between acceptance of disability, coping style, perceived social support, and quality of life among Chinese patients with chronic lymphedema. METHODS: Chronic lymphedema patients were recruited from five tertiary hospitals between May and July 2020 in China. Recruited patients were assessed for quality of life (QOL), acceptance of disability (AOD), coping styles, perceived social support (PSS), and sociodemographic and disease-related factors. Multivariate linear regression models were conducted to examine the multivariate effect of AOD, coping style, PSS, and sociodemographic and disease-related factors on QOL. RESULTS: A total of 163 chronic lymphedema patients were recruited. The mean score of QOL was 2.23 (SD = 0.68). AOD, number of symptoms, acceptance-resignation, avoidance, degree of pain, PSS, and educational level were found to be significant predictors of QOL. CONCLUSION: Chinese patients with chronic lymphedema had moderate levels of QOL. The QOL and specific domains of patients were affected by different factors. Special attention and targeted interventions should be given to improve patients' QOL.

Correlates of stigma for patients with cancer: a systematic review and meta-analysis.

OBJECTIVE: The systematic review and meta-analysis was performed to summarize the available evidence and identify the correlates of cancer stigma. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library, and PsycINFO were electronically searched to identify eligible studies about correlates of stigma for patients with cancer. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of included studies. A meta-analysis was performed using the statistical program R. RESULTS: Thirty-one studies involving a total of 7114 patients were included in the systematic review and meta-analysis. The results of the meta-analysis showed that cancer stigma shared positive associations with male gender, symptoms, depression, anxiety, body image loss, self-blame, social constraint, intrusive thoughts, and ambivalence over emotional expression, and negative associations with income, NK cell subsets, QOL, self-esteem, self-efficacy, cancer screening attendance, doctor's empathy, and medical satisfaction. The results of the descriptive analysis indicated that cancer stigma was positively associated with self-perception of aging, anger, internal attributions, stressful life events, self-perceived burden, and sleep dysfunction, while negatively associated with patient-provider communication and sleep quality. CONCLUSION: Healthcare staff should pay attention to the identified correlates of cancer stigma. The results of our research can inform the design of interventions to reduce stigma and to improve clinical outcomes in people with cancer.

Reticulocalbin-1 knockdown increases the sensitivity of cells to Adriamycin in nasopharyngeal carcinoma and promotes endoplasmic reticulum stress-induced cell apoptosis.

Nasopharyngeal carcinoma (NPC) mainly appears in southeastern Asian countries, including China. Adriamycin (ADM), a type of antitumor drug, is widely applied in treatments against various cancers. Nevertheless, cancer cells will eventually develop drug resistance to ADM. The present study aims to explore the potential role of reticulocalbin-1 (RCN1) in NPC cells resistance to ADM. Microarray-based analysis was used to screen NPC-related genes, with RCN1 acquired for this current study. RCN1 expression in NPC tissues and cells was determined. The biological function of RCN1 on NPC cell apoptosis was evaluated via gain- and loss-of-function experiments in 5-8 F/ADM and 5-8 F cells by delivering si-RCN1 and RCN1-vector. The function of endoplasmic reticulum (ER) stress on cell apoptosis was measured with the involvement of the PERK-CHOP signaling pathway. Furthermore, tumor formation in nude mice was performed to evaluate the survival condition and RCN1 effects in vivo. RCN1 was highly expressed in NPC tissues and cell lines. The increased expression of ER-related proteins ATF4, CHOP, and the extents of IRE1 and PERK phosphorylation were observed. RCN1 knockdown was found to reduce resistance of NPC cells/tissues to ADM while activating ER stress through the activated PERK-CHOP signaling pathway, which further promoted NPC cell apoptosis. These in vitro findings were detected in vivo on tumor formation in nude mice. In conclusion, the present study provides evidence that RCN1 knockdown stimulates ADM sensitivity in NPC by promoting ER stress-induced cell apoptosis, highlighting a theoretical basis for NPC treatment.

Posttreatment Non-Improved Vocal Cord Mobility Indicates the Need of Salvage Surgery for Hypopharyngeal Carcinomas.

INTRODUCTION: We aimed to analyze the relationship between the changed status of vocal cord mobility and survival outcomes. METHODS: Seventy-eight patients with dysfunctional vocal cords and hypopharyngeal carcinomas accepted non-surgical treatment as the initial therapy between May 2009 and December 2016. Vocal cord mobility was assessed before and after the initial non-surgical treatment. The cord mobility status was classified as normal, impaired, and fixed. Patients with improved mobility (IM) (n =56) were retrospectively analyzed for disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) and compared with 22 patients with non-improved mobility (non-IM). RESULTS: Fifty-six (71.8%) patients had improved cord mobility after the initial non-surgical treatment. The non-improved cord mobility was significantly associated with shortened DFS (P=0.005), RFS (P=0.002), and OS (P<0.001). If non-improved cord mobility was regarded as an indicator for local-regional recurrence within 1 year, the sensitivity and the specificity were 60.9%, 87.5% respectively. The multivariate analysis showed that improved cord mobility (P=0.006) and salvage surgery (P=0.015) were both independent protective factors for OS. CONCLUSION: Changes in cord mobility are a key marker for predicting prognosis. Non-improved cord mobility may indicate a high possibility of a residual tumor, therefore, patients whose cord mobility remains dysfunctional or worsens after non-surgical treatment might need an aggressive salvage strategy.