Incidental thyroid carcinomas: experiences related to the surgery of head and neck cancers.

Background: Incidental thyroid carcinomas (ITCs) in patients undergoing head and neck surgery are rare, but there are no standard guidelines for the treatment of this situation. This retrospective study sought to detail our experiences in the treatment of ITCs related to the surgery of head and neck cancers. Methods: We conducted a retrospective analysis of the data about the ITCs in the patients with head and neck cancer, who underwent surgical treatments at Beijing Tongren Hospital in the past 5 years. The number and size of the thyroid nodules, postoperative pathology, follow-up results, and other information were recorded in detail. All the patients underwent surgical treatment and were followed-up for >1 year. Results: A total of 11 patients (10 male and 1 female) with ITC were included in this study. The patients had an average age of 58 years. Most of the patients (72.7%, 8/11) had laryngeal squamous cell cancer, and 7 were diagnosed with thyroid nodules on ultrasound. The surgical procedures for laryngeal and hypopharyngeal cancers included partial laryngectomy, total laryngectomy, and hypopharyngectomy. All the patients underwent thyroid stimulating hormone (TSH) suppression therapy. No recurrence or mortality events from thyroid carcinoma were observed. Conclusions: More attention needs to be paid to ITCs in head and neck surgery patients. Additionally, more research and the long-time follow-up of ITC patients are needed to extend understandings. For patients with head and neck cancers, if the suspicious thyroid nodules are found pre-operatively by ultrasound, fine-needle aspiration (FNA) is recommended. If FNA cannot be performed, the guidelines for thyroid nodules should be followed. In patients with postoperative ITC, TSH suppression therapy and follow-up is indicated.

Analysis of Cause-Specific Mortality in Patients with Retinoblastoma.

Background: Retinoblastoma (RB) is a rare pediatric tumor with a relatively favorable prognosis. However, RB is associated with cause-specific mortality, some of that should be of great importance to clinicians. In this study, we summarize the characteristics of cause-specific mortality from nontumor disease in patients with RB. Methods: This retrospective case series study identified and analyzed cause-specific mortality in patients with RB. The information of cause-specific mortality of RB patients, including detailed clinical characteristics, diagnosis, treatment process, cause-specific mortality classification, and lag time, was assessed. Results: A total of 12 eligible patients were selected from 264 patients who died among 3780 patients diagnosed with RB. The cause-specific mortality rate was 4.5% for all patients with RB who died and 0.3% for all patients with RB. The main nontumor cause-specific mortalities were diseases of the nervous, circulatory, and respiratory systems, which specifically included intracranial infection, cerebral hemorrhage, paraplegia, and respiratory failure. The longest lag time was 42 days from the last chemoradiotherapy or surgery. Conclusion: Nontumor cause-specific mortality is an essential outcome of RB. Thus, intensive care and differentiation during management need to be taken seriously.

Prothrombotic Factors in Obstructive Sleep Apnea: A Systematic Review With Meta-Analysis.

BACKGROUND: Previous studies revealed that the prothrombotic factors in patients with obstructive sleep apnea (OSA) remain controversial. AIM/OBJECTIVE: The aim of the systematic review is to elucidate the relationship between prothrombotic factors and OSA. MATERIALS AND METHODS: This systematic review was performed under the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The literature we investigated was extracted from 4 main medical databases (PubMed, Web of Science, Cochrane Library, and Chinese databases) as of February 2020. We used significant weighted mean differences (SMDs) with 95% CIs from random-effects model. RESULTS: A total of 15 studies comprising 2190 patients were available for the meta-analysis. The pooled results showed that the levels of fibrinogen (SMD = 0.95, 95% CI = 0.26 to 1.65, P = .000), vascular endothelial growth factor (SMD = 0.37, 95% CI = -0.90 to 1.63, P = .000), and plasminogen activator inhibitor 1 (SMD = 0.61, 95% CI = 0.29 to 0.92, P = .040) increased in patients with OSA. There were no statistical differences between groups in terms of d-dimer (P = .108) and platelet counts (P = .233). Subgroup analyses demonstrated that specimen types and age could account for the heterogeneity. CONCLUSIONS AND SIGNIFICANCE: This meta-analysis indicated the relationship between prothrombotic factors in OSA hypopnea. Obstructive sleep apnea-related effects may underline the importance of considering the dysfunction of the hemostatic system. The prothrombotic factors in OSA can influence making a choice of appropriate therapy.

Low expression of TFF3 in papillary thyroid carcinoma may correlate with poor prognosis but high immune cell infiltration.

Background: Papillary thyroid carcinoma (PTC) is one of the most common endocrine malignancies and has a favorable prognosis. However, optimal treatments and prognostic markers have not been clearly identified. Methods: Gene expression data from primary PTC were downloaded from the Gene Expression Omnibus database and subjected to two analyses of differentially expressed genes (DEGs), followed by intersecting individual and integrated DEGs analyses as well as gene set enrichment analysis. Analysis of data from Sequence Read Archive and The Cancer Genome Atlas, immunohistochemistry and qRT-PCR of TFF3 were performed to validate the results. Finally, the relationship between gene expression and disease-free survival as well as immune cell infiltration were investigated. Results: Six critical DEGs and several tumor-enriched signaling pathways were identified. Immunohistochemistry and qRT-PCR validated the low expression of TFF3 in PTC. TFF3 and FCGBP are coexpressed in PTC, and patients with lower gene expression had worse disease-free survival but higher immune cell infiltration. Conclusion: TFF3 was significantly underexpressed and may function with FCGBP synergistically in PTC.

Lay abstract Thyroid cancers are some of the most common endocrine malignancies. However, the optimal treatments and prognostic markers have not been clearly identified. We identified six critical differentially expressed genes and several tumor-enriched signaling pathways in papillary thyroid carcinoma, and found that TFF3 was the most underexpressed gene, as validated by experiment. In addition, TFF3 and FCGBP worked synergistically and may mark prognosis and tumor immune cell infiltration, which may benefit patients with papillary thyroid carcinoma by providing early indication and prompting further basic investigation.

Clinical Heterogeneity of Differentiated Thyroid Cancer between Children Less than 10 Years of Age and Those Older than 10 Years: A Retrospective Study of 70 Cases.

OBJECTIVES: The objectives of this study were to explore the clinical heterogeneity of differentiated thyroid cancer (DTC) between prepubertal children and adolescents and guide clinical treatment. METHODS: A retrospective study included patients with DTC aged ≤19 years in Beijing Children's Hospital from June 2014 to June 2019. All patients were enrolled and divided into 2 subgroups based on the threshold age of 10 years, namely the childhood group (CG) (≤10 years old); and the adolescent group (AG) (between 10 and 19 years old). The χ2 test and Fisher's exact test were used to estimate the effect of risk factors in the 2 age groups. Multivariate binary logistic regression models were conducted to assess the recurrent risk factors. RESULTS: Seventy cases of DTC were included with an average age of 9.94 ± 2.88 years, including 35 in CG and 35 in AG. The most common clinical manifestation was a painless mass in the neck, accounting for 77.1% (54/70) of patients. Compared with the AG, the CG was more likely to have lymph node metastasis (p = 0.022) and distant metastasis (p = 0.041). The CG was more likely to have extrathyroidal extension (p = 0.012) and had a significantly higher recurrence rate than the AG (p = 0.040). Age was an independent variable predictive of recurrence (p = 0.0347). CONCLUSION: Regional invasiveness, cervical lymph node metastasis, and distant metastasis of DTC were more likely to occur in children ≤10 years old. Meanwhile, children ≤10 years old with DTC were more likely to have recurrence than adolescent's postsurgical treatment. Thus, children younger than 10 years of age with DTC should be treated more aggressively.

RB1 germline mutation spectrum and clinical features in patients with unilateral retinoblastomas.

Background: Retinoblastoma is the most common intraocular cancer in children in which above 90% of bilateral cases and 10-25% of unilateral cases have germline RB1 mutations. We summarized the spectrum of RB1 germline mutations and the clinical manifestations of unilateral retinoblastomas to guide clinical treatments.Methods: Two hundred and sixty-three unrelated patients with unilateral retinoblastoma and their parents were included between February 2014 and August 2020. Next-generation sequencing and Sanger sequencing analysis of the core promoter region and exons 1-27 including flanking intronic regions of the RB1 gene were performed. If a germline mutation was identified in a retinoblastoma patient, the parental blood sample was requested to test for the identified mutation.Results: RB1 germline mutations were identified in 39/263 (14.8%) unilateral retinoblastoma patients and 11 (28.2%) had a missense mutation, 10 (25.6%) had nonsense mutations, 2 (5.1%) had frameshifts, 1 (2.6%) had synonymous mutation, and 7 (17.9%) had a large deletion, 2 (5.1%) had splice site mutations, 6 (15.4%) had variant of uncertain significance. Moreover, 27 (69.2%) of 39 patients identified RB1 mutations were predicted to have pathogenic mutation. The median age at diagnosis of patients with identified RB1 pathogenic mutations was 16.9 months and the patients with the wild-type allele was 21.1 months (P = .323).Conclusion: The rate of germline RB1 mutations is 14.8% in our cohort of unilateral retinoblastomas. The high incidence of germline mutations indicates that genetic testing and counseling for families of unilateral retinoblastoma patients would be beneficial.

A population-based analysis of clinical features and lymph node dissection in head and neck malignant neurogenic tumors.

BACKGROUND: The influence of lymph node dissection (LND) on survival in patients with head and neck neurogenic tumors remains unclear. We aimed to determine the effect of LND on the outcomes of patients with head and neck neurogenic tumors. METHODS: Data of patients with surgically treated head and neck neurogenic tumors were identified from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) to investigate the relationship between LND and clinical outcomes by survival analysis. Subgroup analysis was performed in IVa and IVb group. RESULTS: In total, 662 head and neck neurogenic tumor patients (median age: 49.0 [0-91.0] years) met the inclusion criteria, of whom 13.1% were in the IVa group and 86.9% were in the IVb group. The median follow-up time was 76.0 months (range: 6.0-336.0 months), and the 5-year and 10-year overall survival was 82.4% (95% CI, 0.79-0.85) and 69.0% (95% CI, 0.64-0.73). Cox regression analysis revealed older age (P < .001), advanced stage (P = .037), African American race (P = .002), diagnosis before 2004 (P < .001), and chemotherapy administration (P < .001) to be independent negative predictors of overall survival. Kaplan-Meier analysis demonstrated that LND was not a predictor of clinical nodal negativity (cN0) in either IVa or IVb patients. CONCLUSIONS: In head and neck neurogenic patients, LND may not impact the outcome of cN0 in either IVa or IVb group. These data can be recommended in guiding surgical plan and future studies.

Clinical Features and Survival of Chinese Children With Trilateral Retinoblastoma During 2006-2019: A Retrospective Multicenter Study.

PURPOSE: To summarize the clinical features and survival of Chinese patients with trilateral retinoblastoma (TRb), which may help guide early diagnosis and more effective treatments. DESIGN: Retrospective case series. METHODS: Clinical records of patients with TRb were reviewed to identify clinical characteristics and outcomes. TRb was diagnosed mainly based on imaging findings of an enlarged solid pineal or sellar mass. Mutation screening was performed using peripheral blood leucocyte DNA from 3 patients. RESULTS: Fourteen patients with TRb were identified from among 3,789 patients with retinoblastoma (0.4%). Thirteen patients had bilateral retinoblastoma and 1 patient had unilateral disease. The follow-up results revealed that 2 patients survived, 3 patients were lost to follow-up, and 9 patients died. The mean overall survival was 9.8 months (95% confidence interval: 2.3-17.2), and the 2-year survival rate was 18.8% (95% confidence interval: 2.9-45.1) based on Kaplan-Meier estimates. Cox regression multivariate analysis showed metastasis at TRb diagnosis was an independent variable of overall survival (hazard ratio: 15.8; 95% confidence interval: 0.24-5.29; P = .032). Three germline mutations in the RB1 gene were detected via next-generation sequencing. CONCLUSIONS: TRb is a rare intracranial mid-line neuroblastic disease. Increased awareness of this disease could guide early detection, which has been associated with improved outcomes.

Clinical Features of Children with Retinoblastoma and Neuroblastoma.

PURPOSE: Retinoblastoma and neuroblastoma are the most common malignant extracranial solid tumors in children. This study aimed to summarize the clinical features, especially the delayed diagnosis in children with retinoblastoma and neuroblastoma. METHODS: In a single hospital-based case-control study, a retrospective cohort of 175 children with retinoblastoma and neuroblastoma diagnosed from January 2016 to January 2018 were reviewed. The state of enucleation in retinoblastomas and pathological prognosis in neuroblastomas were outcome indicators. Hereby, the patients were divided into two groups, and clinical features including age at presentation and delayed diagnosis were compared. RESULTS: A total of 112 patients with retinoblastoma and 63 with neuroblastoma were included. In the retinoblastoma cohort, the median age at presentation was 17.2 months (0.3-110 months). The mean delay of diagnosis was 1.6 ± 2.3 months, and the rate of enucleation was 61.6%. Unilateral disease, the International Classification of Intraocular Retinoblastoma (IIRC) stage E, and delay of diagnosis over 2.5 months were independent risk factors of ocular outcomes. Notably, the risk of enucleation was increased by 474% when the delay was longer than 2.5 months. In the neuroblastoma cohort, the delay of diagnosis of the unfavorable histology (UH) group was longer than that of the favorable histology (FH) group (1.9 months vs. 1.4 months, P=.487). The levels of serum ferritin and neuron-specific enolase were higher in the UH group than in the FH group (P < .05). CONCLUSIONS: This study summarized the clinical features and diagnosis biomarkers of retinoblastoma and neuroblastoma patients in China. These results might help to focus on early detection and treatment in children with retinoblastoma and neuroblastoma.

Pan-cancer analysis reveals the role of long non-coding RNA LINC01614 as a highly cancer-dependent oncogene and biomarker.

Long intergenic non-coding RNA 1614 (LINC01614) is highly expressed in several malignant tumor types, suggesting that it may act as an oncogene. However, the specific roles of LINC01614 in malignant tumors have remained elusive. To examine the expression pattern of LINC01614 in various malignancies, a comprehensive pan-cancer analysis was performed using public databases, including 53 normal tissue types and 32 cancer datasets with samples from 9,091 patients. The results were validated using reverse transcription-quantitative PCR analysis of tissue specimens from patients. LINC01614 expression was upregulated in most malignant tumors, thus demonstrating diagnostic potential. Furthermore, upregulation of LINC01614 was associated with poor overall survival in the majority of cases. However, the association with clinical outcome was highly cancer-dependent; LINC01614 appeared to be an oncogene and diagnostic/prognostic biomarker in cancers of the digestive, respiratory, nervous and endocrine systems, as well as breast and head and neck cancer, but not in the cancers of the reproductive system or some of the urinary system. High LINC01614 expression was also markedly associated with the epithelial-mesenchymal transition (EMT) and associated signaling pathways. Overall, the present results suggest that LINC01614 is an EMT-associated oncogene that influences the metastasis and prognosis of several cancers, thus highlighting its potential as a novel diagnostic and prognostic marker.

Prognostic value of long non-coding RNA GHET1 in cancers: a systematic review and meta-analysis.

BACKGROUND: A number of studies have demonstrated the critical role of long non-coding RNA gastric cancer high expressed transcript 1 (GHET1) in many cancers. This meta-analysis provides an evidence-based evaluation of the prognostic role of GHET1 in cancer. MATERIALS AND METHODS: Literature searches were conducted in several databases including Medline, Cochrane, EMBASE, CNKI, and Wanfang. The pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were used to evaluate the role of GHET1 in cancer. The study protocol was registered at PROSPERO (ID: CRD42018111252). RESULTS: Sixteen studies, containing 1315 patients, were analyzed in this meta-analysis. The pooled results indicated that GHET1 overexpression was significantly associated with poor overall survival (OS) and disease-free survival (DFS) in cancer. Moreover, up-regulation of GHET1 expression predicted larger tumor size, positive lymph node metastasis, positive distant metastasis, and advanced TNM (tumor-node-metastases) stage in human cancers. CONCLUSION: There is a significant correlation between up-regulation of GHET1 and both poor prognosis and advanced clinicopathological cancer characteristics. GHET1 may be a potential prognostic predictor for human cancers.

Matrix metalloproteinase 9 (MMP9) level and MMP9 -1562C>T in patients with obstructive sleep apnea: a systematic review and meta-analysis of case-control studies.

BACKGROUND: The peripheral level of matrix metalloproteinase (MMP)-9 and polymorphism of MMP9 -1562C>T in patients with obstructive sleep apnea (OSA) remains controversial. Therefore, the aims of this systemic review and meta-analysis are to assess the MMP9 level in OSA patients and identify the relationship between MMP9 -1562C>T and OSA susceptibility. METHODS: This systematic review was performed following the PRISMA guideline. We searched for studies in major databases, identifying those indexed from inception to July 3, 2019 which related to MMP9 level, MMP9 -1562C>T and OSA. The pooled standardized mean differences (SMDs) and 95% confidence interval (CI) of MMP9 levels were calculated. In addition, the relationship between MMP9 -1562C>T and OSA susceptibility was assessed by three genetic models. The heterogeneity analysis and calculation of the pooled odds ratio (OR) were also performed, followed by quality assessment using the Newcastle-Ottawa Scale (NOS). RESULTS: In sum, our review included 15 eligible studies regarding MMP9 level and three regarding MMP9 -1562C>T. The pooled results showed that peripheral level of MMP9 was increased in OSA patients (SMD = 1.37; 95% CI = 1.15-1.59). Furthermore, significant difference of MMP9 level can be found between severe and mild-to-moderate OSA patients (SMD = 28.17; 95% CI = 4.23-52.11) or between moderate-severe and mild OSA (SMD = 36.62; 95% CI = 12.19-61.04). However, no relationship was observed between MMP9 -1562C>T and OSA susceptibility in three genetic models (Homozygote model, OR = 1.37; 95% CI = 0.87-2.18); (Recessive model, OR = 1.42; 95% CI = 0.83-2.42); (Allele model, OR = 1.07; 95% CI = 0.96-1.18). CONCLUSIONS: This systemic review and meta-analysis indicated that the level of MMP9 was increased in patients with OSA and this increase is relevant to OSA severity. Moreover, the relationship between MMP9 -1562 C>T and OSA susceptibility has currently not been proven by current merging values. Further analyses with larger sample size are required to verify these associations.