Safety and efficacy of microwave ablation for symptomatic benign thyroid nodules in children.

OBJECTIVE: To evaluate the efficacy and safety of microwave ablation (MWA) for the treatment of symptomatic benign thyroid nodules in children. METHODS: A retrospective study of MWA for the treatment of 34 symptomatic benign thyroid nodules in 25 children was conducted. Volume reduction ratio (VRR), technique efficacy, symptom score, cosmetic score, and thyroid function were used to evaluate the efficacy of the technique. The associated complications and side effects were recorded. RESULTS: The participants were followed for at least 6 months (median 12 months, range 6-48 months). After MWA treatment, the volumes of the targeted nodules decreased gradually (median volume 5.86 mL before MWA and 0.34 mL at the final follow-up assessment), the VRR achieved was up to 85.03% at the final follow-up assessment, and the technical efficacy at this time was 91.2%. The subjective and objective nodule-related symptoms were also ameliorated. The circulating hormone concentrations reflecting thyroid function remained within their normal ranges in all the participants after one month of follow-up. The procedure had no major complications. CONCLUSIONS: MWA seems to be an effective and safe technique for the treatment of symptomatic benign thyroid nodules in pediatric patients. CLINICAL RELEVANCE STATEMENT: Microwave ablation is a safe and effective method to treat symptomatic benign thyroid nodules in pediatric patients. This treatment may be selected if the patient or parents are not suitable or refuse to undergo surgery. KEY POINTS: • Microwave ablation is effective in reducing the volume of benign thyroid nodules and ameliorating nodule-related symptoms in pediatric patients. • Microwave ablation is a safe method in children, with low complications. • Microwave ablation does not affect the circulating thyroid hormone concentrations of children.

Socioeconomic inequalities in cancer incidence and access to health services among children and adolescents in China: a cross-sectional study.

BACKGROUND: Despite the substantial burden caused by childhood cancer globally, childhood cancer incidence obtained in a nationwide childhood cancer registry and the accessibility of relevant health services are still unknown in China. We comprehensively assessed the most up-to-date cancer incidence in Chinese children and adolescents, nationally, regionally, and in specific population subgroups, and also examined the association between cancer incidence and socioeconomic inequality in access to health services. METHODS: In this national cross-sectional study, we used data from the National Center for Pediatric Cancer Surveillance, the nationwide Hospital Quality Monitoring System, and public databases to cover 31 provinces, autonomous regions, and municipalities in mainland China. We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China through stratified proportional estimation. We classified regions by socioeconomic status using the human development index (HDI). Incidence rates of 12 main groups, 47 subgroups, and 81 subtypes of cancer were reported and compared by sex, age, and socioeconomic status, according to the third edition of the International Classification of Childhood Cancer. We also quantified the geographical and population density of paediatric oncologists, pathology workforce, diagnoses and treatment institutions of paediatric cancer, and paediatric beds. We used the Gini coefficient to assess equality in access to these four health service indicators. We also calculated the proportions of cross-regional patients among new cases in our surveillance system. FINDINGS: We estimated the incidence of cancer among children (aged 0-14 years) and adolescents (aged 15-19 years) in China from Jan 1, 2018, to Dec 31, 2020. An estimated 121 145 cancer cases were diagnosed among children and adolescents in China between 2018 and 2020, with world standard age-standardised incidence rates of 122·86 (95% CI 121·70-124·02) per million for children and 137·64 (136·08-139·20) per million for adolescents. Boys had a higher incidence rate of childhood cancer (133·18 for boys vs 111·21 for girls per million) but a lower incidence of adolescent cancer (133·92 for boys vs 141·79 for girls per million) than girls. Leukaemias (42·33 per million) were the most common cancer group in children, whereas malignant epithelial tumours and melanomas (30·39 per million) surpassed leukaemias (30·08 per million) in adolescents as the cancer with the highest incidence. The overall incidence rates ranged from 101·60 (100·67-102·51) per million in very low HDI regions to 138·21 (137·14-139·29) per million in high HDI regions, indicating a significant positive association between the incidence of childhood and adolescent cancer and regional socioeconomic status (p<0·0001). The incidence in girls showed larger variation (48·45% from the lowest to the highest) than boys (36·71% from lowest to highest) in different socioeconomic regions. The population and geographical densities of most health services also showed a significant positive correlation with HDI levels. In particular, the geographical density distribution (Gini coefficients of 0·32-0·47) had higher inequalities than population density distribution (Gini coefficients of 0·05-0·19). The overall proportion of cross-regional patients of childhood and adolescent cancer was 22·16%, and the highest proportion occurred in retinoblastoma (56·54%) and in low HDI regions (35·14%). INTERPRETATION: Our study showed that the burden of cancer in children and adolescents in China is much higher than previously nationally reported from 2000 to 2015. The distribution of the accessibility of health services, as a social determinant of health, might have a notable role in the socioeconomic inequalities in cancer incidence among Chinese children and adolescents. With regards to achieving the Sustainable Development Goals, policy approaches should prioritise increasing the accessibility of health services for early diagnosis to improve outcomes and subsequently reduce disease burdens, as well as narrowing the socioeconomic inequalities of childhood and adolescent cancer. FUNDING: National Major Science and Technology Projects of China, National Natural Science Foundation of China, Chinese Academy of Engineering Consulting Research Project, Wu Jieping Medical Foundation, Beijing Municipal Administration of Hospitals Incubating Program.

Young Children Allergic Rhinitis Questionnaire is a novel tool for allergy screening in children.

BACKGROUND: There are a limited number of validated questionnaires available for use in the clinical screening for allergic rhinitis (AR) in children ≤3 years old. We developed a novel self-reported questionnaire and assessed its accuracy and reliability. METHODS: After establishing a pool of items, which were screened by experts, the Young Children Allergic Rhinitis Questionnaire (YCAR-Q) was administered to a birth cohort in the Shunyi District (Beijing, China). The electronic version of the YCAR-Q was distributed through the online community. Children were invited to visit a physician for examination. The diagnostic criteria included symptoms, physical examination findings, and specific serum immunoglobulin E tests. Each item on the questionnaire was evaluated, and the questionnaire's internal consistency, content validity, criterion-related validity, and diagnostic accuracy were assessed. RESULTS: The six-item YCAR-Q was distributed to 7423 parents, and 3037 valid questionnaires were recovered. In total, 1521 children visited a physician for examination, of which 82 were found to have AR. In terms of internal consistency, Cronbach's coefficient was 0.777 and all six questionnaire items were retained. The average scale-level content validity index value was 1. The area under the curve was 0.759. The total scores ranged from 0 to 6, and the cutoff value for diagnosing AR was 3, with a sensitivity of 68.29% and a specificity of 76.58%. CONCLUSIONS: This cross-sectional study indicated that the YCAR-Q could detect AR in children ≤3 years old. This brief and simple test may be used effectively in clinical practice.

Surgical Treatment of Cervicothoracic Junction Lesions in Children: A Series of 18 Cases.

Purpose The cervicothoracic junction (CTJ) lesions in children is rare. Surgical treatment for lesions at the cervicothoracic junction is challenging due to the presence of the great vessels and other thoracic structures. There are no criteria that help select a surgical approach to manage cervicothoracic lesions in children so far. This study focuses on the cervicothoracic junction lesions in children(C7-T4) and provides experience for the appropriate surgical approach for them.Methods: This retrospective study enrolled 18 children with cervicothoracic junction lesions who underwent surgical treatment in our Hospital from January 2015 to September 2019. They were evaluated with preoperative CT or MR imaging and diagnosed postoperatively by pathological examination.Results: This study included 2 patients with congenital lesions, 4 patients with benign lesions, and 12 patients with malignant lesions. Lesions with a margin below C7-T3, including benign and malignant tumors could be resected using a simple low anterior cervical approach (LACA). Congenital lesions and benign lesions with a margin below T4 could also be treated with this approach. Two-thirds of the malignant lesions below T4 were resected through the LACA combined with video-assisted thoracoscopic surgery (VATS). 1 patient with malignant lesion extending to T4 was removed by the LACA combined with posterolateral thoracotomy.Conclusions: The lesions at the cervicothoracic junction (C7-T4) in children may be managed with the simple LACA used in most patients. For malignancies extending to the T4 level, LACA and VATS could be performed in combination to resect lesions completely and invasively.

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.

Clinical implications of TPO and AOX1 in pediatric papillary thyroid carcinoma.

BACKGROUND: Thyroid carcinoma is a common pediatric head and neck cancer, of which papillary thyroid cancer (PTC) is the most common type. Previously, we found that thyroid peroxidase (TPO) and aldehyde oxidase 1 (AOX1) were differentially expressed in PTC. This study explored the clinical importance of TPO and AOX1 in the diagnosis and prognosis of PTC in children. METHODS: Both TPO and AOX1 expression in PTC were analyzed using datasets from Gene Expression Omnibus (GEO). TPO and AOX1 protein levels in plasma from patients with PTC and non-tumor controls were detected via enzyme-linked immunosorbent assay (ELISA). The diagnostic accuracy of TPO and AOX1 was assessed using receiver operating characteristic (ROC) curve analysis. The association between gene expression levels and patient survival was explored using the Kaplan-Meier plotter online database. RESULTS: The results revealed that TPO and AOX1 expression was significantly downregulated in four independent datasets (GSE33630, GSE27155, GSE3678, and GSE3467). TPO and AOX1 protein levels in blood plasma were significantly decreased in patients with PTC. Quantitative analysis demonstrated that TPO and AOX1 levels in plasma had satisfactory predictive performance and the ability to discriminate PTC from healthy samples. Prognostic analysis demonstrated that low levels of TPO and AOX1 were markedly associated with poor survival in patients with PTC. CONCLUSIONS: In summary, these results implied that TPO and AOX1 could serve as novel biomarkers for the diagnosis and prognosis of pediatric PTC.

Endoscopy-assisted, transoral submucosal coblation for pediatric retropharyngeal lymphatic malformations.

OBJECTIVE: Retropharyngeal lymphatic malformations (LMs) are uncommon congenital anomalies. Open surgery, sclerotherapy and various pharmaceutical agents have been described to manage these lesions. However, when such lesions involve the retropharyngeal space with evidence of airway compromise, none of the above aforementioned modalities has shown superior result without repeated imaging and procedures. We describe the use of radiofrequency ablation (Coblation) in an endoscopic-assisted, transoral approach as a one-off treatment for pediatric retropharyngeal lymphatic malformations. METHODS: Six patients with retropharyngeal lymphatic malformations, presented with airway compromise, were treated with endoscopic-assisted, transoral submucosal coblation in our unit between April 2015 to August 2018. We retrospectively reviewed their medical records, imaging and endoscopic findings. RESULTS: Five out of our six patients had LMs involving only the retropharyngeal space, who received the coblation as their sole treatment. One patient with extensive LMs involving multiple neck compartments received coblation to the retropharyngeal part as an adjunct procedure. The average operation time was 62.8 min, and the average intraoperative blood loss was 3.8 ml. All patients were safely extubated immediately after the surgery. None required admission to pediatric intensive care unit (PICU), nor prolonged dysphagia reported. They were observed for 2-5 days post operatively. The average follow up was 28 months (1-5 years) and none required re-operation to date. CONCLUSIONS: We presented our approach and outcome of 6 children with endoscopic-assisted, transoral submucosal coblation to retropharyngeal lymphatic malformation. We believe it is a safe and effective primary treatment to these patients, and a possible adjunct to complex vascular malformation involving multiple sites.

Bioinformatics analysis to screen key genes in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, and its incidence has been on the increase in recent years. However, the molecular mechanism of PTC is unclear and misdiagnosis remains a major issue. Therefore, the present study aimed to investigate this mechanism, and to identify key prognostic biomarkers. Integrated analysis was used to explore differentially expressed genes (DEGs) between PTC and healthy thyroid tissue. To investigate the functions and pathways associated with DEGs, Gene Ontology, pathway and protein-protein interaction (PPI) network analyses were performed. The predictive accuracy of DEGs was evaluated using the receiver operating characteristic (ROC) curve. Based on the four microarray datasets obtained from the Gene Expression Omnibus database, namely GSE33630, GSE27155, GSE3467 and GSE3678, a total of 153 DEGs were identified, including 66 upregulated and 87 downregulated DEGs in PTC compared with controls. These DEGs were significantly enriched in cancer-related pathways and the phosphoinositide 3-kinase-AKT signaling pathway. PPI network analysis screened out key genes, including acetyl-CoA carboxylase beta, cyclin D1, BCL2, and serpin peptidase inhibitor clade A member 1, which may serve important roles in PTC pathogenesis. ROC analysis revealed that these DEGs had excellent predictive performance, thus verifying their potential for clinical diagnosis. Taken together, the findings of the present study suggest that these genes and related pathways are involved in key events of PTC progression and facilitate the identification of prognostic biomarkers.

Correlation between TERT C228T and clinic-pathological features in pediatric papillary thyroid carcinoma.

The aims of the present study were to reveal the prevalence of the TERT C228T mutation in pediatric papillary thyroid carcinoma (PPTC) and to further investigate the role of the TERT C228T mutation in PPTC. We also tested another TERT mutation, TERT C250T, although this was not detected in PPTC patients. In this study, 48 patients with PPTC (41 with classic PPTC) were enrolled. DNA was extracted from PPTC tissues and TERT C228T mutation analysis was performed. Chi-squared analysis, Fisher's exact test, and a t-test were applied to test the significance of differences. The TERT C228T mutation presented in 13 (27.1%) of the 48 PPTC patients and 10 (24.4%) of the 41 classical PPTC patients. There were significant differences between PPTC patients with the TERT C228T mutation and those without in terms of modified radical neck dissection, multifocality, capsular invasion, extrathyroidal invasion, and American Joint Committee on Cancer (AJCC) tumor stage (P<0.05). In classical PPTC, there were additional significant differences in other clinic-pathological features, such as AJCC nodal stage (P=0.009) and American Thyroid Association (ATA) PPTC stage (P=0.021) between patients with and without the TERT C228T mutation. These findings indicate that the TERT C228T mutation is significantly correlated with certain aggressive clinic-pathological features of PPTC.

Clinical analysis of surgical treatment for head and neck lymphatic malformations in children: a series of 128 cases.

Background: Lymphatic malformations (LMs) are caused due to abnormal lymphatic development, and mainly occur in neonates or young children. At present, the role of surgery in the treatment of head and neck LMs is still controversial, focusing mainly on surgical efficacy and indications. Objective: This study aimed to explore the effect and influential factors of surgical treatment in children with head and neck LMs, hoping to provide a basis for rational selection of surgical indications. Methods: This retrospective study enrolled 128 children with head and neck LMs and underwent surgical treatment in Beijing Children's Hospital from May 2007 to June 2016. They were classified into three morphological groups: macrocystic, microcystic, and mixed. Based on de Serres staging, they were divided into five groups: stage I to V. The local lesion control rate, complication rate, and recurrence rate were summarized and analyzed. Results: The rate of completely controlled and almost completely controlled in cases with head and neck LMs was 71.1%. The postoperative complication rate was 13.3%, and the postoperative recurrence rate was 11.9%. Statistically significant difference was found for local lesion control and postoperative recurrence rates between different morphological and clinical staging groups. Furthermore, the complication rate showed a significant difference between different morphological groups, but not between clinical staging groups. Conclusions: Surgical resection in children with macrocystic, low-stage, or neck-limited LMs demonstrated better therapeutic effect, with fewer complications. However, the effect remained poor and had more complications for microcystic, diffused and high-stage patients. High stage and incomplete resection are considered as the main factors for postoperative recurrence. Current staging system for LMs has important predictive value in the prognosis of head and neck LMs. For LMs in posterior pharyngeal space, plasma ablation has certain advantages.

Up-regulated lipocalin-2 in pediatric thyroid cancer correlated with poor clinical characteristics.

BACKGROUND: The incidence of thyroid cancer is fast increasing in both adults and children. The pediatric thyroid cancer had often already progressed to a more advanced stage of the disease at diagnosis. Early detection of pediatric thyroid cancer has been a problem for many years. Lipocalin-2 (Lcn2) has been reported to be over-expressed in cancers of diverse histological origin and it facilitates tumorigenesis by promoting survival, growth, and metastasis. METHODS: The plasma Lcn2 concentration of 28 Chinese papillary thyroid cancer (PTC) children and 24 healthy controls was measured. Immunostaining for Ki-67 of tumor tissue from PTC children was performed. The expression levels of Lcn2 and NFκB in PTC tissue and peri-carcinoma tissue of PTC children were measured through Western blot. RESULTS: The plasma concentration of Lcn2 was significantly elevated in pediatric PTC patients compared with healthy controls. Besides, the plasma Lcn2 concentration significantly correlated with clinical characteristics, NFκB level, and Ki-67 positive rate of nucleus in tissue of PTC. CONCLUSION: This is the first study to evaluate the plasma Lcn2 in pediatric PTC patients. It is possible that the plasma Lcn2 may be a new biomarker of pediatric thyroid cancer. Further studies are needed to explore the definite role and mechanism of Lcn2 in thyroid cancer, which will help to explore novel diagnostic or therapeutic strategies.

CO2 laser cauterization approach to congenital pyriform sinus fistula.

OBJECTIVE: To evaluate the efficacy of CO2 laser cauterization with suspension microlaryngoscopy as a definitive surgical treatment for pediatric Congenital Pyriform Sinus Fistula (CPSF). MATERIAL AND METHODS: This is a cohort retrospective study. Thyroid function and cervical ultrasonography examinations were performed before operation. Enhanced magnetic resonance imaging (MRI) was performed on patients with a repeated infection (≥2 times) and/or if they had a prior open surgery. Patients were divided into two groups: the <8-year-old group and the ≥8-year-old group. The differences in the number of cauterization procedures between the two age groups and between the initial treatment and the retreatment groups were analyzed. RESULTS: CO2 laser cauterizations with suspension microlaryngoscopy were performed for 104 CPSF patients. No complications occurred. Three patients had a recurrence in the follow-up. The number of surgical cauterization operations was fewer than 3 in 85.1% of the patients. There was no significant difference in the number of cauterizations among the different age groups or between the initial treatment and retreatment groups (P>0.05). CONCLUSION: CO2 laser cauterization with suspension microlaryngoscopy is a safe, effective, and minimally invasive approach to CPSF with optimal patient outcomes. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level III.

Correlation between BRAF V600E mutation and clinicopathological features in pediatric papillary thyroid carcinoma.

In adults, the presence of the BRAF V600E mutation in papillary thyroid cancer (PTC) has been demonstrated to be strongly associated with aggressive cancer-cell characteristics and poor patient prognosis. In contrast, the frequency of this mutation in pediatric PTC has undergone limited study, and the few available estimates range from 0 to 63%. Furthermore, the role of the BRAF V600E mutation in pediatric PTC is controversial; thus, the present study aimed to investigate the prevalence and role of the BRAF V600E mutation in 48 pediatric patients with PTC, aged 3-13 years. Of these patients, 41 were diagnosed with classic PTC, five were found to have a follicular variant of PTC, and two to exhibit a diffuse sclerosing PTC variant. The BRAF V600E mutation was identified to be present in 35.4% of the 48 analyzed patients, and in 41.5% of the patients diagnosed with classical PTC. Furthermore, the presence of the BRAF V600E mutation was found to be associated with a patient age at diagnosis of less than ten years (P=0.011), the performance of a thyroidectomy (P=0.03), exhibited tumor multifocality (P=0.02) and/or extra-thyroidal invasion (P=0.003), and both a low MACIS (Metastases, Age, Completeness of resection, Invasion, Size)(P=0.036) and AMES (Age, Metastasis, Extent of tumor, Size)(P=0.001) score. Together, these data suggest that the presence of the BRAF V600E mutation may be negatively correlated with partial aggressive clinicopathological features of pediatric PTC.

MicroRNA-365a-3p promotes tumor growth and metastasis in laryngeal squamous cell carcinoma.

MicroRNAs (miRNAs) are increasingly recognized as oncogenes or tumor suppressors in laryngeal squamous cell carcinoma (LSCC). In this study, we analyzed the roles of miR-365a-3p, miR-143-5p, and miR-494-3p in LSCC using Annexin V/propidium iodide double staining and flow cyto-metry, along with a Transwell migration and invasion assay. The results showed that miR-365a-3p inhibitor significantly facilitated cell apoptosis and suppressed cell cycle progression, migration, and invasion in Hep-2 cells. However, miR-143-5p and miR-494-3p had no such influences. We then investigated the role of miR-365a-3p in LSCC in vivo and found that miR-365a-3p inhibitor suppressed LSCC xenograft tumor growth and metastasis in xenograft mouse models. Moreover, miR-365a-3p inhibitor significantly decreased the expression of p-AKT (Ser473), which indicated that miR-365a-3p can mediate PI3K/AKT signaling pathway transduction via p-AKT (Ser473) in LSCC. The data suggest that miR-365a-3p may act as an oncomiR and may promote growth and metastasis in LSCC via the PI3K/AKT signaling pathway, and thus miR­365a-3p may be a potential therapeutic target for treatment of LSCC.

[Relationship of alcohol drinking and tea consumption with the risk of nasopharynx cancer among Chinese population: a meta-analysis].

OBJECTIVE: To evaluate the relationship and strength of association for alcohol drinking and tea consumption with the riskS of nasopharynx cancer among Chinese population so as to provide control rationales for nasopharynx cancer in China. METHODS: A systematic search of 3 Chinese electronic databases (CNKI, VIP, Wanfang) and 3 English databases (Pubmed, ScienceDirect and SpringerLink) up to March 2013 was performed. Two reviewers independently conducted the literature search, examined eligibility and performed data extraction and quality evaluations. Pooled odd ratio (OR) value and 95%CI value were calculated with random-effects model weighted with inverse of variances. RESULTS: A total of 14 studies (including 3 cohort and 11 case-control) involving 6559 cases of nasopharynx cancer and 10 567 controls from 6 provinces were included. The pooled OR between alcohol drinking and risks of nasopharynx cancer was 1.12 (95%CI: 0.98-1.26; I(2) = 44.5%, P = 0.037). Compared with the non-drinkers, the risks of nasopharynx cancer for regular drinkers and occasional drinkers were 1.18 (95%CI: 1.00-1.38; I(2) = 0.0%, P = 0.578) and 0.76 (95%CI: 0.65-0.89; I(2) = 33.4%, P = 0.212). And the association of tea consumption with the risks of nasopharynx cancer was 0.53 (95%CI: 0.43-0.60; I(2) = 17.9%, P = 0.301). CONCLUSIONS: In China, occasional alcohol drinking may decrease the risks of nasopharynx cancer while regular drinking elevates the risks. And there is significantly protective effect for tea consumption on the risks of nasopharynx cancer.