Application of Machine Learning and Deep EfficientNets in Distinguishing Neonatal Adrenal Hematomas From Neuroblastoma in Enhanced Computed Tomography Images.

Background: The aim of the study was to employ a combination of radiomic indicators based on computed tomography (CT) imaging and machine learning (ML), along with deep learning (DL), to differentiate between adrenal hematoma and adrenal neuroblastoma in neonates. Methods: A total of 76 neonates were included in this retrospective study (40 with neuroblastomas and 36 with adrenal hematomas) who underwent CT and divided into a training group (n = 38) and a testing group (n = 38). The regions of interest (ROIs) were segmented by two radiologists to extract radiomics features using Pyradiomics package. ML classifications were done using support vector machine (SVM), AdaBoost, Extra Trees, gradient boosting, multi-layer perceptron (MLP), and random forest (RF). EfficientNets was employed and classified, based on radiometrics. The area under curve (AUC) of the receiver operating characteristic (ROC) was calculated to assess the performance of each model. Results: Among all features, the least absolute shrinkage and selection operator (LASSO) logistic regression selected nine features. These radiomics features were used to construct radiomics model. In the training cohort, the AUCs of SVM, MLP and Extra Trees models were 0.967, 0.969 and 1.000, respectively. The corresponding AUCs of the test cohort were 0.985, 0.971 and 0.958, respectively. In the classification task, the AUC of the DL framework was 0.987. Conclusion: ML decision classifiers and DL framework constructed from CT-based radiomics features offered a non-invasive method to differentiate neonatal adrenal hematoma from neuroblastoma and performed better than the clinical experts.

Postnatal treatment and evolution patterns of giant fetal hepatic hemangioma: a case series of 29 patients.

OBJECTIVES: To explore the clinical characteristics, postnatal treatment and prognosis of giant fetal hepatic hemangioma (GFHH). METHOD: Retrospective analysis was performed on children with giant fetal hepatic hemangioma (maximum tumor diameter > 40 mm) diagnosed by prenatal ultrasound and MRI from December 2016 to December 2020. These patients were observed and treated at the Children's Hospital of Fudan University after birth. The clinical data were collected to analyze the clinical characteristics, treatment, and prognosis of GFHH using independent sample t tests or Fisher's exact tests. RESULTS: Twenty-nine patients who were detected by routine ultrasound in the second and third trimester of pregnancy with giant fetal hepatic hemangiomas were included. The first prenatal ultrasound diagnosis of gestational age was 34.0 ± 4.3 weeks, ranging from 22 to 39 weeks. Of the patients, 28 had focal GFHHs and 1 had multifocal GFHHs. Surgery was performed, and the diagnosis was confirmed histopathologically in two patients. There were 8 cases with echocardiography-based evidence of pulmonary hypertension, 11 cases had a cardiothoracic ratio > 0.6, and 4 cases had hepatic arteriovenous fistula (AVF). The median follow-up time was 37 months (range: 14-70 months). During the follow-up, 12 patients received medical treatment with propranolol as the first-line therapy. The treatment group had a higher ratio of cardiothoracic ratio > 0.6 (P = 0.022) and lower albumin levels (P = 0.018). Four (14.8%) lesions showed postnatal growth before involuting. Complete response was observed in 13 (13/29) patients, and partial response was observed in 16 (16/29) patients. CONCLUSIONS: Fetal giant hepatic hemangioma is mainly localized, and its clinical outcome conforms to RICH (rapidly involuting) and PICH (partially involuting), but some fetal giant hepatic hemangiomas will continue to grow after birth and then gradually decrease. For uncomplicated giant fetal hepatic hemangioma, postnatal follow-up is the main concern, while those with complications require aggressive medical treatment. Propranolol may have no effect on the volume change of GFHH.

Deciphering pathological behavior of pediatric medullary thyroid cancer from single-cell perspective.

Background: Pediatric medullary thyroid cancer (MTC) is one of the rare pediatric endocrine neoplasms. Derived from C cells of thyroid glands, MTC is more aggressive and more prompt to metastasis than other types of pediatric thyroid cancer. The mechanism remains unclear. Methods: We performed single-cell transcriptome sequencing on the samples of the primary tumor and metastases lymph nodes from one patient diagnosed with MTC, and it is the first single-cell transcriptome sequencing data of pediatric MTC. In addition, whole exome sequencing was performed and peripheral blood was regarded as a normal reference. All cells that passed quality control were merged and analyzed in R to discover the association between tumor cells and their microenvironment as well as tumor pathogenesis. Results: We first described the landscape of the single-cell atlas of MTC and studied the interaction between the tumor cell and its microenvironment. C cells, identified as tumor cells, and T cells, as the dominant participant in the tumor microenvironment, were particularly discussed in their development and interactions. In addition, the WES signature of tumor cells and their microenvironment were also described. Actively immune interactions were found, indicating B cells, T cells and myeloid cells were all actively participating in immune reaction in MTC. T cells, as the major components of the tumor microenvironment, proliferated in MTC and could be divided into clusters that expressed proliferation, immune effectiveness, and naive markers separately.

The Cellular and Molecular Landscape of Synchronous Pediatric Sialoblastoma and Hepatoblastoma.

Sialoblastoma (SBL) is an infrequent embryonal malignant tumor originating from the salivary gland, resembling primitive salivary gland anlage, whereas hepatoblastoma (HB) is the most common pediatric liver malignancy. The simultaneous occurrence of both tumors is extremely rare. Here we reported a case of a 6-month-old infant diagnosed with synchronous SBL and HB. The patient received neoadjuvant chemotherapy followed by surgical resection. Fresh tissues of both tumors were collected before and after chemotherapy, which were further profiled by whole exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq). WES analysis revealed potential somatic driver mutation PIK3CA p.Glu454Lys for SBL and canonical mutation CTNNB1 p.Ser45Pro for HB. No shared somatic variants or common copy number alterations were found between SBL and HB primary tumor samples. Though scRNA-seq, single-cell atlases were constructed for both tumors. SBL may recapitulate a pre-acinar stage in the development of salivary gland, including basaloid, duct-like, myoepithelial-like, and cycling phenotypes. In the meantime, HB was composed of tumor cells resembling different stages of the liver, including hepatocyte-like, hepatic progenitor-like, and hepatoblast-like cells. After chemotherapy, both tumors were induced into a more mature phenotype. In terms of transcriptional signatures, SBL and HB showed enhanced expression of epithelial markers KRT8, KRT18, and essential embryo development genes SDC1, MDK, indicating the disruption of normal embryo epithelium development. Finally, heterozygous deleterious germline mutation BLM and FANCI were identified which could predispose the patient to higher cancer risk. It partially explained the reason for the co-occurrence of SBL and HB. Taken together, we provided valuable resources for deciphering cellular heterogeneity and adaptive change of tumor cells after chemotherapy for synchronous SBL and HB, providing insights into the mechanisms leading to synchronous pediatric tumors.

Tumor Suppressive Role of MUC6 in Wilms Tumor via Autophagy-Dependent ß-Catenin Degradation.

Wilms tumor is the most common renal malignancy in children. Known gene mutations account for about 40% of all wilms tumor cases, but the full map of genetic mutations in wilms tumor is far from clear. Whole genome sequencing and RNA sequencing were performed in 5 pairs of wilms tumor tissues and adjacent normal tissues to figure out important genetic mutations. Gene knock-down, CRISPR-induced mutations were used to investigate their potential effects in cell lines and in-vivo xenografted model. Mutations in seven novel genes (MUC6, GOLGA6L2, GPRIN2, MDN1, MUC4, OR4L1 and PDE4DIP) occurred in more than one patient. The most prevalent mutation was found in MUC6, which had 7 somatic exonic variants in 4 patients. In addition, TaqMan assay and immunoblot confirmed that MUC6 expression was reduced in WT tissues when compared with control tissues. Moreover, the results of MUC6 knock-down assay and CRISPR-induced MUC6 mutations showed that MUC6 inhibited tumor aggression via autophagy-dependent ß-catenin degradation while its mutations attenuated tumor-suppressive effects of MUC6. Seven novel mutated genes (MUC6, GOLGA6L2, GPRIN2, MDN1, MUC4, OR4L1 and PDE4DIP) were found in WT, among which MUC6 was the most prevalent one. MUC6 acted as a tumor suppressive gene through autophagy dependent ß-catenin pathway.

Single-cell transcriptional profiling reveals the heterogeneity in embryonal rhabdomyosarcoma.

ABSTRACT: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, and embryonal rhabdomyosarcoma is the most typical type of rhabdomyosarcoma. The heterogeneity, etiology, and origin of embryonal rhabdomyosarcoma remain unknown.After obtaining the gene expression data of every cell in the tumor tissue by single-cell RNA sequencing, we used the Seurat package in R studio for quality control, analysis, and exploration of the data. All cells are divided into tumor cells and non-tumor cells, and we chose tumor cells by marker genes. Then, we repeated the process to cluster the tumor cells and divided the subgroups by their differentially expressed genes and gene ontology/Kyoto Encyclopedia of Genes and Genomes analysis. Additionally, Monocle 2 was used for pseudo-time analysis to obtain the evolution trajectory of cells in tumor tissues.Tumor cells were divided into 5 subgroups according to their functions, which were characterized by high proliferation, sensing and adaptation to oxygen availability, enhanced epigenetic modification, enhanced nucleoside phosphonic acid metabolism, and ossification. Evolution trajectory of cells in tumor tissues is obtained.We used pseudo-time analysis to distinguish between mesenchymal stem cells and fibroblasts, proved that embryonal rhabdomyosarcoma in the pelvic originated from skeletal muscle progenitor cells, showed the evolutionary trajectory of embryonal rhabdomyosarcoma, and improved the method of evaluating the degree of malignancy of embryonal rhabdomyosarcoma.

Single-Cell Characterization of Malignant Phenotypes and Developmental Trajectories of Adrenal Neuroblastoma.

Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive research, the underlying developmental origin of NB remains unclear. Using single-cell RNA sequencing, we generate transcriptomes of adrenal NB from 160,910 cells of 16 patients and transcriptomes of putative developmental cells of origin of NB from 12,103 cells of early human embryos and fetal adrenal glands at relatively late development stages. We find that most adrenal NB tumor cells transcriptionally mirror noradrenergic chromaffin cells. Malignant states also recapitulate the proliferation/differentiation status of chromaffin cells in the process of normal development. Our findings provide insight into developmental trajectories and cellular states underlying human initiation and progression of NB.

Long-term prognosis of low-risk neuroblastoma treated by surgery alone: an experience from a single institution of China.

BACKGROUND: Low-risk neuroblastomas have favorable biologic characteristics. Children Oncology Group (COG) proposed that surgical resection of the primary tumor was sufficient. We evaluated the long-term prognosis of surgery alone for patients with low-risk neuroblastoma in China. METHODS: A total of 34 patients with low-risk neuroblastoma were treated in our center between Jan 2009 and Dec 2013. The medical records of these patients were reviewed. RESULTS: The primary lesion was located in the adrenal gland in 19 patients, the retroperitoneum in 5, the posterior mediastinum in 9 and the neck in 1. The tumor diameters and volumes were 1.80-10.0 cm (average 5.5 ± 2.3 cm) and 1.28-424.10 cm3 (average 58.81 ± 92.00 cm3), respectively. The stages of the patients were as follows: stage I in 25, stage II in 7, and stage IVs in 2. All patients were in the low-risk group according to COG risk stratification criteria. No patients showed MYCN amplification. The primary tumors of all patients were completely resected. Nine adrenal tumors were completely resected by laparoscopy. All patients were successfully followed for 66-115 (average 89.71 ± 16.17) months. Recurrence was observed in 4 patients. In addition to one local recurrence, another three recurrences were metastases. The lesions were effectively controlled in all patients with recurrences. All patients survived, including 28 cases of tumor-free survival; the 4-year overall and event-free survival rates were both 100%. CONCLUSIONS: Surgery alone is a safe and effective treatment strategy for low-risk neuroblastoma. Recurrent lesions may be controlled and treated by rescue chemotherapy and surgery.

Expression Profiling Identifies Circular RNA Signature in Hepatoblastoma.

BACKGROUND/AIMS: Hepatoblastoma is the most common malignant pediatric liver cancer. circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of circRNAs in hepatoblastoma is still unknown. METHODS: Circular RNA microarray was conducted to identify hepatoblastoma-related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in hepatoblastoma. MTT assays, Ki67 staining, and Transwell assays were conducted to clarify the role of circRNA in hepatoblastoma in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in hepatoblastoma cell. RESULTS: 869 differentially expressed circRNAs were identified between hepatoblastoma and adjacent normal liver samples, including 421 up-regulated circRNAs and 448 down-regulated circRNAs. The significant enriched GO term of hepatoblastoma-related circRNAs in biological process, cellular component, and molecular function were "chromosome organization", "cytoplasm", and "organic cyclic compound binding". Tight junction signaling pathway was ranked the Top 1 potentially affected by circRNA-mediated regulatory network. circ_0015756 was significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. circ_0015756 silencing decreased hepatoblastoma cell viability, proliferation, and invasion in vitro. circ_0015756 acted as miR-1250-3p sponge to regulate hepatoblastoma cell function. CONCLUSIONS: circRNAs are involved in the pathogenesis of hepatoblastoma. circ_0015756 is a promising target for the prognosis, diagnosis, and treatment of hepatoblastoma.

Long non-coding RNA-CRNDE: a novel regulator of tumor growth and angiogenesis in hepatoblastoma.

Long non-coding RNAs (lncRNAs) are involved in many biological processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. They have emerged as key players in the pathology of several tumors, including hepatoblastoma. In this study, we elucidate the biological and clinical significance of CRNDE up-regulation in hepatoblastoma. CRNDE is significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. CRNDE knockdown reduces tumor growth and tumor angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, and angiogenic effect in vitro. Mechanistic studies show that CRNDE knockdown plays its anti-proliferation and anti-angiogenesis role via regulating mammalian target of rapamycin (mTOR) signaling. Taken together, this study reveals a crucial role of CRNDE in the pathology of hepatoblastoma. CRNDE may serve as a promising diagnostic marker and therapeutic target for hepatoblastoma.

Hypersplenism Associated With Late-Presenting Congenital Diaphragmatic Hernia: A Rare Combination. Case Report.

Congenital diaphragmatic hernia (CDH) is a rare developmental anomaly of the diaphragm that mainly presents mainly in newborns. Even less common is late-onset CDH associated with hypersplenism. We report a 10-year-old male who presented with coughing, blood-stained sputum, and fever. He was diagnosed with CDH complicating hypersplenism after computed tomography was done. The patient was treated by CDH repair and splenectomy, and remained asymptomatic at 6-month follow-up. Computed tomography can be an important diagnostic option in this rare combination of CDH and hypersplenism, and surgical intervention is strongly recommended.

Primary gastric tumors in infants and children: 15 cases of 20-year report.

PURPOSE: Primary gastric tumors in infants and children are rare, and their diagnosis and treatment have not been standardized to date. The objective of the present retrospective study was to analyze the clinical characteristics of these tumors and explore possible improvements in their diagnosis and treatment. METHODS: The study included 15 children with a diagnosis of primary gastric tumor confirmed by pathology. Clinical manifestations, diagnostic methods and treatment were analyzed retrospectively, and postoperative conditions were assessed in follow-up evaluations. RESULTS: There were nine boys and six girls aged 8 months to 13 years. The main presenting symptoms were abdominal pain, melena, fever of undetermined origin and pallor. Children were assessed by ultrasound, CT and upper gastrointestinal barium meal or gastroscopy and showed abdominal blockage or polypoid space-occupying lesions. All patients underwent surgery as initial treatment, and four patients received postoperative chemotherapy. During the follow-up period from 3 to 92 months, four cases were lost, one patient died of metastatic disease, two patients showed recurrence, and the remaining patients were alive without recurrence or progression. CONCLUSIONS: Owing to the atypical and often asymptomatic presentation of primary gastric tumors, careful evaluation using imaging modalities is critical in suspicious cases. Most primary gastric tumors in infants and children are benign or borderline. The prognosis, except in gastric carcinoma, is excellent with close follow-up when complete resection is achieved.

Congenital mesoblastic nephroma: Clinical analysis of eight cases and a review of the literature.

Congenital mesoblastic nephroma (CMN) is a mesenchymal renal tumor. The aim of the present study was to review the clinical characteristics and outcome of CMN in infants. A retrospective file review was conducted of eight cases of CMN treated at the Children's Hospital of Fudan University between 2004 and 2012. Ultrasound and computerized tomography scans had been performed on all eight patients. Two cases presented with a solid tumor and exhibited pathological features consistent with those of classic CMN, five cases exhibited cystic, hemorrhagic and necrotic characteristics, with calcification and pathology consistent with the cellular variant of CMN and one case presented with a solid tumor, which exhibited pathological features consistent with ceullular CMN. Histology confirmed classic CMN in two patients and cellular CMN in six patients. For surgical intervention, four cases had radical nephrectomy, one case had a half nephrectomy and three cases had tumor enucleation performed. Two cases had received pre-operative chemotherapy, but exhibited no response, and three cases received post-operative chemotherapy. Two patients were lost to follow-up, but the remaining six patients survived to the end of follow-up without further complications. The mean follow-up time was 24.6 months. In conclusion, the differential diagnosis between CMN and Wilms' tumor is critical. Imaging characteristics are partially correlated with pathological characteristics. Surgery is the main treatment for CMN, but pre-operative chemotherapy is not particularly effective. The efficacy of post-operative chemotherapy requires further investigation, but the prognosis is positive.

Small intestinal tubular adenoma in a pediatric patient with Turner syndrome.

Turner syndrome (TS) is a female chromosomal disorder caused by the lack of an X chromosome. The loss of this chromosome may result in the deficiency of tumor-suppressive or DNA repair genes, leading to tumorigenesis. Recombinant human growth hormone (GH) has been popularly used for treatment in TS patients for growth promotion. Although treatment with GH has been correlated with precancerous and cancerous lesions in TS children, its associations with gastric or colonic tumors, especially ileal tubular adenomas, have not been reported frequently. We here report a case of a 16-year-old patient with TS and tubular adenoma of the small intestine. Whether the ileal adenoma was caused by TS itself or GH therapy was discussed.

Conservative management of neonatal hepatic hemangioma: a report from one institute.

PURPOSE: To summarize the conservative treatment of neonatal hepatic hemangioma at one institute. PATIENTS AND MATERIALS: Fifteen cases of neonatal hepatic hemangioma were managed in our hospital during the previous 5 years. Initial symptoms, combination symptoms, diagnosis, and treatment were analyzed. RESULTS: Initial symptoms were abdominal mass, hepatomegaly, jaundice, and pneumonia. Combination symptoms were multiple skin hemangiomas, pneumonia, and cardiac insufficiency. Ultrasound and CT showed the typical characteristics of the liver hemangioma. There were three types of hepatic hemangioma: nine cases had a single focus, four cases were multiple foci, and two had diffuse changes in the liver. The diameter of a single focus in this group was about 53-99 mm. Four cases of single focus received resection and two received biopsy. Six cases received corticosteroid treatment. The other five cases were kept under observation only. Those with cardiac insufficiency and pneumonia received diuretics and antibiotic treatment. One neonate with cardiac insufficiency and pneumonia had postoperative MODS and died. One patient having multi-focus in the liver gave up the treatment after biopsy. Other patients were followed-up at 5-17 months. Two cases that received total tumor resection did not have recurrence. In those who received conservative therapy, all hemangiomas disappeared within 1 year. CONCLUSION: The diagnosis of hepatic hemangioma can be made from symptomology, ultrasound, and CT; pathologic samples are not necessary. Corticosteroid therapy is the widely used therapy. Proactive therapy for congestive heart failure is helpful for those endangering liver hemangioma. Surgery can increase the risk of complications and is not advised for treatment of neonatal hepatic hemangioma.

[Effects of zearalenone on the proliferation of SK-N-SH human neuroblastoma cells].

OBJECTIVE: To investigate effects of zearalenone (ZEA) on the proliferation of SK-N-SH human neuroblastoma cells in vitro and its possible mechanism. METHODS: SK-N-SH cells were cultured in estrogen-free improved minimum essential medium and divided into 5 groups based on different treatments: group 1, without treatment; group 2, treated with 17beta-estradiol (E(2)); group 3, treated with ZEA; group 4, treated with both E(2) and ICI 182780; group 5, treated with both ZEA and ICI 182780. Absorbance value (AV) was determined at the time point of 0, 24, 48 and 72 hours, and DNA proliferation index (PI) at 72 hours. Flow cytometer, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were employed to monitor cell apoptosis. RESULTS: At 24, 48 and 72 hours, the AV of group 3 were 1.39, 1.32, and 1.22 times to those of group 1, respectively. PI in group 3 was 1.43 times of that in group 1 at 72 hours. The results of group 2 were similar to those in group 3. At the same time, the growth of cells was inhibited by ICI 182780 despite the presence of E(2) and ZEA. Apoptosis cells were abundant in group 1 and ICI 182780 groups, but little in E(2) and ZEA groups. CONCLUSION: ZEA might promote the proliferation of SK-N-SH cells to a level similar to that of E(2), which might probably be brought about via estrogen receptor pathways and depressing apoptosis.

[Therapeutic effect of continuous veno-venous hemodiafiltration on systemic inflammatory response syndrome induced by cecum perforate peritonitis in piglets].

OBJECTIVE: Most of the therapeutic strategies for systemic inflammatory response syndrome (SIRS) is not effective. This study was to investigate the effect of continuous veno-venous hemodiafiltration (CVVHDF) on SIRS induced by cecum perforate peritonitis in piglets. METHODS: Twelve piglets (weighing 7-9 kg) were randomly divided into two groups: control and CVVHDF (n=6). The piglets of both groups were subjected to a cecum puncture to induce peritonitis which caused SIRS. After SIRS occurred the piglets of the CVVHDF group immediately received the CVVHDF therapy for 6 hrs, with a blood flow rate of 20 mL/min, a replacement rate of 300 mL/h, and a dialysis rate of 600 mL/h. The heart rate (HR), mean artery blood pressure (MABP), respiratory rate (RR), arterial blood gas analysis and blood cells count were measured and recorded at baseline and onset of SIRS, and 2, 4 and 6 hrs after SIRS occurred. RESULTS: When SIRS occurred, the HR and RR increased and the MABP, artery oxygen pressure (PaO2) and the count of white cells decreased in both groups. The HR of the CVVHDF group decreased significantly at 2 hrs (P < 0.05) and remained lower until 6 hrs after CVVHDF therapy (P < 0.01) compared with that of the control group. The RR of the CVVHDF group was significantly lower than that of the control group 6 hrs after CVVHDF therapy (P < 0.05). The MABP of the CVVHDF group increased significantly 4 and 6 hrs after therapy compared with that of the control group (P < 0.01, P < 0.05 respectively). There were no significant differences in temperature, PaO2 and blood cells count between the two groups during the experiment. CONCLUSIONS: CVVHDF has a positive effect on hemodynamics in piglets with SIRS induced by cecum perforate peritonitis.