Impact of the COVID-19 pandemic on the demographic and disease burden of pediatric malignant solid tumors in China: a single-center, cross-sectional study.

Background: With the development of the novel coronavirus disease 2019 (COVID-19), China implemented measures in an attempt to control the infection rate. We conducted a single-center, cross-sectional study to ascertain the impact of the COVID-19 pandemic on the equitable availability of medical resources for children diagnosed with malignant solid tumors in China. Methods: Data on the demographics, clinical characteristics, and medical expenses of 876 patients diagnosed with neuroblastoma, rhabdomyosarcoma (RMS), Wilms tumor, hepatoblastoma (HB), Ewing sarcoma (ES), and central nervous system (CNS) tumors from 2019 to 2021, during the COVID-19 pandemic, were retrospectively collected from the National Center for Children's Health. The Pearson χ2 test and Mann-Whitney test were performed to analyze the differences among variables. Results: Except for the regional origin of children with tumors during the epidemic, no significant differences were found in the demographic or clinical characteristics of patients at initial diagnosis. The number of patients from northern China and northeastern China who attended Beijing Children's Hospital (BCH) increased after the outbreak of COVID-19 (P=0.001). There was no significant alteration observed in the frequency of hospitalizations per individual per annum (P=0.641) or the mean expense incurred per individual per hospitalization (P=0.361). In addition, the medical insurance coverage rate of real-time settlement increased year by year. Conclusions: After the COVID-19 outbreak, the origin of patients with solid tumor who visited BCH was concentrated in the northern region of China. COVID-19 had no impact on the other demographic factors, clinical characteristics, or economic burden of patients with pediatric malignant solid tumors.

Hepatoblastoma with neonatal necrotizing enterocolitis: Two case reports.

We report two children with hepatoblastoma (HB) with a history of neonatal necrotizing enterocolitis (NEC). Case 1 was diagnosed with HB at 5 months of age. Liver enlargement was found during the NEC operation at 3 months of age and then was clinically diagnosed by imaging. After six chemotherapy courses, a partial hepatectomy was performed. Three months after ceasing the chemotherapy, a chest computed tomography scan suggested that distant metastasis of the tumor should be considered, and the lesion was removed. However, 9 months after the operation, alpha-fetoprotein concentrations were increased, and abdominal imaging showed a recurrence of the tumor in situ, resulting in a hepatectomy. Case 2 was diagnosed with NEC shortly after birth and underwent an intestinal resection and anastomosis 1 month later. He was diagnosed with HB at 3 years of age. Hepatectomy was performed after five courses of chemotherapy. Chemotherapy was stopped after 10 courses, and alpha-fetoprotein concentrations were normal. At present, both children have survived and are in a healthy condition. Physicians should be aware of the possibility of HB and a history of NEC in children. Premature birth and low birth weight are common factors leading to the pathogenesis of HB and NEC. The association between these two diseases requires further study.

Nectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastoma.

Neuroblastoma (NB) is a pediatric cancer of the peripheral sympathetic nervous system and represents the most frequent solid malignancy in infants. Nectin2 belongs to the immunoglobulin superfamily and has been shown to play a role in tumorigenesis. In the current study, we demonstrate that serum Nectin2 level is increased in NB patients compared with that in healthy controls and Nectin2 level is correlated with neuroblastoma international neuroblastoma staging system (INSS) classification. There is a positive correlation between Nectin2 level and shorter overall survival in NB patients. Knockdown of Nectin2 reduces the migration of SH-SY5Y and SK-N-BE2 cells and induces their apoptosis and cell cycle arrest. RNA-seq analysis demonstrates that Nectin2 knockdown affects the expressions of 258 genes, including 240 that are upregulated and 18 that are downregulated compared with negative controls. qRT-PCR and western blot analysis confirm that ANXA2 expression is decreased in Nectin2-knockdown SH-SY5Y cells, consistent with the RNA-seq results. ANXA2 overexpression rescues the percentage of apoptotic NB cells induced by Nectin2 knockdown and compensates for the impact of Nectin2 knockdown on cleaved caspase3 and bax expressions. In addition, western blot analysis results show that ANXA2 overexpression rescues the effect of Nectin2 knockdown on MMP2 and MMP9 expressions. The current data highlight the importance of Nectin2 in NB progression and the potential of Nectin2 as a novel candidate target for gene therapy.

Quantitative proteomics identifies and validates urinary biomarkers of rhabdomyosarcoma in children.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma with poor prognosis in children. The 5-year survival rate for early RMS has improved, whereas it remains unsatisfactory for advanced patients. Urine can rapidly reflect changes in the body and identify low-abundance proteins. Early screening of tumor markers through urine in RMS allows for earlier treatment, which is associated with better outcomes. METHODS: RMS patients under 18 years old, including those newly diagnosed and after surgery, were enrolled. Urine samples were collected at the time points of admission and after four cycles of chemotherapy during follow-up. Then, a two-stage workflow was established. (1) In the discovery stage, differential proteins (DPs) were initially identified in 43 RMS patients and 12 healthy controls (HCs) using a data-independent acquisition method. (2) In the verification stage, DPs were further verified as biomarkers in 54 RMS patients and 25 HCs using parallel reaction monitoring analysis. Furthermore, a receiver operating characteristic (ROC) curve was used to construct the protein panels for the diagnosis of RMS. Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) software were used to perform bioinformatics analysis. RESULTS: A total of 251 proteins were significantly altered in the discovery stage, most of which were enriched in the head, neck and urogenital tract, consistent with the most common sites of RMS. The most overrepresented biological processes from GO analysis included immunity, inflammation, tumor invasion and neuronal damage. Pathways engaging the identified proteins revealed 33 common pathways, including WNT/ß-catenin signaling and PI3K/AKT signaling. Finally, 39 proteins were confirmed as urinary biomarkers for RMS, and a diagnostic panel composed of 5 candidate proteins (EPS8L2, SPARC, HLA-DRB1, ACAN, and CILP) was constructed for the early screening of RMS (AUC: 0.79, 95%CI = 0.66 ~ 0.92). CONCLUSIONS: These findings provide novel biomarkers in urine that are easy to translate into clinical diagnosis of RMS and illustrate the value of global and targeted urine proteomics to identify and qualify candidate biomarkers for noninvasive molecular diagnosis.

Clinical features and prognosis of paediatric rhabdomyosarcoma with bone marrow metastasis: a single Centre experiences in China.

BACKGROUND: The aim of this study was to summarize the clinical characteristics, therapeutic effects and prognosis of patients with rhabdomyosarcoma (RMS) and bone marrow metastasis, improve the understanding of this disease. METHOD: This was a single-institution retrospective study involving the children with RMS, who presented with bone marrow metastasis at initial presentation to our hospital between 1st, Jan, 2006 and 31st, Dec,2019. Follow-up concluded on 31st, Dec, 2020 and the clinical data were collected and analysed. RESULT: Between 1st Jan 2006 and 31st Dec 2019, 13 eligible patients presented to our hospital, including 10 males and 3 females, these eligible patients accounted for 4.5% of all RMS patients. The median age at onset was 5.6 years (range 1.7-14 years). The patients not only had unfavourable primary sites, but also had multiple metastases. The bone marrow aspirate samples of the patients comprised 8-95% blast-like cells. Nine of 13 patients were misdiagnosed with haematological malignancies or other solid tumours. With respect to histology, four of 13 children were classified as embryonal RMS and nine as alveolar RMS. Eleven patients underwent PAX-FOXO1 fusion testing; eight had the POX- FOXO1 fusion gene. Immunohistochemically(IHC) analysis revealed that the tumour cells were positive for Desmin, Vimentin, Myo-D1 and Myogenin. More importantly, the patients had extremely poor prognoses, the median EFS was 12.0 months (range 3-28.3 months) and the median OS was 27.0 months (range6-46.2 months). CONCLUSION: This study demonstrates that children with RMS and bone marrow metastasis usually exhibit atypical primary sites and multiple metastases, with presentation mimicking haematological malignancies or other solid tumors at initial presentation. Pathology and IHC analysis combined with POX-FOXO1 fusion gene detections can effectively confirm the diagnosis. These patients are more likely to relapse or progress during early treatment and are prone to intracranial metastasis. While multidisciplinary therapy combined with Temozolomide may prevent it, further prospective research is required to evaluate the therapeutic effects.

Chromosome 10 abnormality predicts prognosis of neuroblastoma patients with bone marrow metastasis.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in children. It is known for high heterogeneity and concealed onset. In recent years, the mechanism of its occurrence and development has been gradually revealed. The purpose of this study is to summarize the clinical characteristics of children with NB and abnormal chromosome 10, and to investigate the relationship between the number and structure of chromosome 10 abnormalities and NB prognosis. METHODS: Chromosome G-banding was used at the time of diagnosis to evaluate the genetics of chromosomes in patients with NB and track their clinical characteristics and prognosis. All participants were diagnosed with NB in the Medical Oncology Department of the Beijing Children's Hospital from May 2015 to December 2018 and were followed up with for at least 1 year. RESULTS: Of all 150 patients with bone marrow metastases, 42 were clearly diagnosed with chromosomal abnormalities. Thirteen patients showed abnormalities in chromosome 10, and chromosome 10 was the most commonly missing chromosome. These 13 patients had higher LDH and lower OS and EFS than children with chromosomal abnormalities who did not have an abnormality in chromosome 10. Eight patients had both MYCN amplification and 1p36 deletion. Two patients had optic nerve damage and no vision, and one patient had left supraorbital metastases 5 months after treatment. CONCLUSIONS: The results indicated that chromosome 10 might be a new prognostic marker for NB. MYCN amplification and 1p36 deletion may be related to chromosome 10 abnormalities in NB. Additionally, NB patients with abnormal chromosome 10 were prone to orbital metastases.

Infectious lung masses misdiagnosed as metastatic rhabdomyosarcoma: Two case reports.

Rhabdomyosarcoma (RMS) with regional lymph node involvement has a high rate of distant metastases. Lung is the most common site, accounting for 70% of all metastases. The differential diagnosis of lung lesions due to an infectious aetiology versus metastases is usually evaluated by computed tomography (CT) or magnetic resonance imaging. However, it is rare for patients of RMS to present with infectious nodules or masses in the lung during follow-up. More importantly, infections can mimic the imaging characteristics of metastatic RMS in CT. We report two such cases where children diagnosed with head and neck embryonal RMS with lymph node metastasis, presented with pulmonary masses 0.5 and 4 years after end of treatment, without the typical signs and symptoms suggestive of an infection. Chest CT suggested a provisional diagnosis of metastases and biopsies confirmed infectious aetiology (Mycobacterium tuberculosis, Cryptococcus).