Whole-tumoral metabolic heterogeneity in 18F-FDG PET/CT is a novel prognostic marker for neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the heterogeneity of whole-body tumor lesions remains clinical challenge. This study aims to quantify whole-tumoral metabolic heterogeneity (WMH) derived from whole-body tumor lesions, and investigate the prognostic value of WMH in NB. METHODS: We retrospectively enrolled 95 newly diagnosed pediatric NB patients in our department. Traditional semi-quantitative PET/CT parameters including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. These PET/CT parameters were expressed as PSUVmax, PSUVmean, PSUVpeak, PMTV, PTLG for primary tumor, WSUVmax, WSUVmean, WSUVpeak, WMTV, WTLG for whole-body tumor lesions. The metabolic heterogeneity was quantified using the areas under the curve of the cumulative SUV-volume histogram index (AUC-CSH index). Intra-tumoral metabolic heterogeneity (IMH) and WMH were extracted from primary tumor and whole-body tumor lesions, respectively. The outcome endpoints were overall survival (OS) and progression-free survival (PFS). Survival analysis was performed utilizing the univariate and multivariate Cox proportional hazards regression. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic curve (ROC). RESULTS: During follow up, 27 (28.4%) patients died, 21 (22.1%) patients relapsed and 47 (49.5%) patients remained progression-free survival, with a median follow-up of 35.0 months. In survival analysis, WMTV and WTLG were independent indicators of PFS, and WMH was an independent risk factor of PFS and OS. However, IMH only showed association with PFS and OS. In addition to metabolic parameters, the International Neuroblastoma Staging System (INSS) was identified as an independent risk factor for PFS, and neuron-specific enolase (NSE) served as an independent predictor of OS. CONCLUSION: WMH was an independent risk factor for PFS and OS, suggesting its potential as a novel prognostic marker for newly diagnosed NB patients.

Risk factors, impact and treatment of postoperative lymphatic leakage in children with abdominal neuroblastoma operated on by laparotomy.

BACKGROUND: Lymphatic leakage is one of the postoperative complications of neuroblastoma. The purpose of this study is to summarize the clinical characteristics and risk factors of lymphatic leakage and try to find effective prevention and treatment measures. METHODS: A retrospective study included 186 children with abdominal neuroblastoma, including 32 children of lymphatic leakage and 154 children of non-lymphatic leakage. The clinical information, surgical data, postoperative abdominal drainage, treatment of lymphatic leakage and prognosis of the two groups were collected and analyzed. RESULTS: The incidence of lymphatic leakage in this cohort was 14% (32 children). Through univariate analysis of lymphatic leakage group and non-lymphatic leakage group, we found that lymphatic leakage increased the complications, prolonged the time of abdominal drainage and hospitalization, and delayed postoperative chemotherapy (p < 0.05). In this cohort, the median follow-up time was 46 (95% CI: 44-48) months. The follow-up data of 7 children were partially missing. 147 children survived, of which 23 had tumor recurrence (5 children recurred in the surgical area). 37 children died, of which 32 had tumor recurrence (9 children recurred in the operation area). In univariate analysis, there was no statistical difference in overall survival (p = 0.21) and event-free survival (p = 0.057) between lymphatic leakage group and non-lymphatic leakage group, while 3-year cumulative incidence of local progression was higher in lymphatic leakage group (p = 0.015). However, through multivariate analysis, we found that lymphatic leakage did not affect event-free survival, overall survival and cumulative incidence of local progression in children with neuroblastoma. Resection of 5 or more lymphatic regions was an independent risk factor for lymphatic leakage after neuroblastoma surgery. All 32 children with lymphatic leakage were cured by conservative treatment without surgery. Of these, 75% (24/32) children were cured by fat-free diet or observation, 25% (8/32) children were cured by total parenteral nutrition. The median drain output at diagnosis in total parenteral nutrition group was higher than that in non-total parenteral nutrition group (p < 0.001). The cut-off value was 17.2 ml/kg/day. CONCLUSIONS: Lymphatic leakage does not affect the prognosis of children with neuroblastoma, but long-term drain output caused by lymphatic leakage will still adversely affect postoperative complications and follow-up treatment, which requires attention and active treatment measures. More attention should be paid to the children with 5 or more lymphatic regions resection, and the injured lymphatic vessels should be actively found and ligated after tumor resection to reduce the postoperative lymphatic leakage. Early application of total parenteral nutrition is recommended for those who have drain output at diagnosis of greater than 17.2 ml/kg/day. LEVEL OF EVIDENCE: Level III, Treatment study (Retrospective comparative study).

Preparation of hyperbranched hydrophobic nano-silica and its superior needling-effect in PDMS defoam agent.

Hydrophobic nano silica powder is a kind of important synergist to silicone defoaming agents. The large pore volume and branched chain conformation of silica nanoparticles present superior effects on defoaming properties. However, silica nanoparticles synthesized by liquid phase easily aggregate and pore collapse because of their high surface activity and polarity, leading to poorer dispersity and limited practicability. In this paper, a novel hydrophobic silica with a hyperbranched structure was designed through in-situ modifying method with hexamethyldisilazane (HMDS) and polydimethylsiloxane (PDMS) in the liquid phase. The trimethylsilanol generated by HMDS hydrolysis reacts quickly with the highly active hydroxyl groups on the silica, causing the surface properties of the nanoparticles to transform from polar to non-polar properties. The steric hindrance of the trimethyl silicon and the reduction of the surface polarity effectively prevent silica pores from collapsing and maintain the macropore structures to realize the hyperbranched silica. At the same time, the -Si (CH3)2- from PDMS endowed the hyperbranched silica with excellent hydrophobicity. When applied in the defoaming agent, the hydrophobicity of silica contributes to dewetting the foams, and the hyperbranched spatial structures play an enhanced needling effect. Therefore, this hydrophobic hyperbranched silica exhibited a surprising defoaming effect, which significantly reduced the defoaming time from 464.4 s to less than 2 s, superior to commercial defoaming silica (155.3 s). The defoaming efficiency reached 100 % within 2 s of the end of the shaking, and the defoamer antifoaming ability was improved to reach 27.5 min, which was 77 % higher than that of commercial defoamer.

A Primary Report 166 Cases of Abdominal or Pelvic Neuroblastoma Surgery Utilizing the International Neuroblastoma Surgical Report Form (INSRF).

BACKGROUND AND AIMS: Surgery is pivotal in the management of neuroblastoma (NB), particularly in patients with Image-Defined Risk Factors (IDRFs). The International Neuroblastoma Surgical Report Form (INSRF) was introduced to enhance surgical reporting quality and analyze the defining role of extensive surgery in NB. This study reports our experience with INSRF and explores new criteria for evaluating the extent of surgical resection. METHODS: INSRF was deployed to critically analyze 166 patients with abdominal or pelvic NB who underwent surgery at our department between October 2021 and June 2023. Patient demographics, clinical characteristics, surgical datasets, and postoperative complications were described in detail. Receiver operating characteristic (ROC) curves were used to explore a new method to evaluate the extent of resection. A questionnaire was formulated to obtain attitudes/feedback and commentary from surgical oncologists with INSRF. RESULTS: 166 neuroblastoma patients with a median disease age 36.50 months. This study collated 320 INSRF reports. Among the 166 index cases, 137 were documented by two surgeons, with a concordance rate of 16.78%. Items with high inconsistency were (i) the extent of tumor resection (29.20%), (ii) renal vein involvement (25.55%), (iii) abdominal aorta encasement (16.79%), and (iv) mesenteric infiltration (17.52%). According to INSRF, the extent of resection was complete excision in 86 (51.81%) patients, minimal residual tumor < 5 cm3 in 67 (40.36%) patients, and incomplete excision > 5 cm3 in 13 (7.83%) patients. In ROC curve analysis, the number of vessels encased by tumors > 3 had a high predictive value in determining that a tumor could not be completely resected (AUC 0.916, sensitivity 0.838, specificity 0.826) using INSRF as the gold standard reference. The questionnaires showed that surgeons agreed that the extent of resection and tumor involvement of organ/vascular structures were important, while the definition and intervention(s) of intraoperative complications were less operational and understandable. CONCLUSIONS: INSRF has significant clinical application in neuroblastoma surgery. The extent of resection can be predicted based on the number of tumor-encased blood vessels. Supplementary information should be considered with the INSRF to aid practitioner reporting. Multicenter studies are needed to explore the defining role of INSRF in NB surgical management.

Diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in pediatric opsoclonus myoclonus ataxia syndrome presenting with neuroblastoma.

BACKGROUND: Early precision diagnosis and effective treatment of opsoclonus myoclonus ataxia syndrome (OMAS) patients presenting with neuroblastoma can prevent serious neurological outcomes. OBJECTIVE: To assess the diagnostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging in pediatric OMAS with neuroblastoma. MATERIALS AND METHODS: A retrospective evaluation of 45 patients diagnosed with OMAS who underwent 18F-FDG PET/CT was performed. A univariate analysis was performed to compare clinical characteristics between OMAS with and without neuroblastoma. Univariate and multivariate logistic regression analyses were applied to identify independent risk factors for OMAS with neuroblastoma and to develop the clinical model. Finally, independent risk factors and PET/CT were fitted to build the combined model for the diagnosis of OMAS with neuroblastoma and presented as a nomogram. Receiver operating characteristic curve, decision curve, and calibration curve analyses were conducted to evaluate the performance of the models. RESULTS: Among 45 patients, 27 were PET/CT-positive, 23/27 lesions were neuroblastoma, and four were false positives. One of the false positive patients was confirmed to be adrenal reactive hyperplasia by postoperative pathology, and the symptoms of OMAS disappeared in the remaining three cases during clinical follow-up. The average maximal standardized uptake value of PET/CT-positive lesions was 2.6. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT were 100%, 81.8%, 85.2%, 100%, and 91.1%, respectively. Age at diagnosis, lactate dehydrogenase, and neuron-specific enolase showed statistically significant differences between OMAS with and without neuroblastoma. Lactate dehydrogenase was identified as the independent risk factor to develop the clinical model, and the clinical model demonstrated an area under the curve (AUC) of 0.82 for the diagnosis of OMAS with neuroblastoma, with an AUC as high as 0.91 when combined with PET/CT. The decision curve analysis and calibration curve demonstrated that the nomogram had good consistency and clinical usefulness. CONCLUSION: In patients with OMAS, 18F-FDG PET/CT has a high diagnostic accuracy in detecting tumors of the neuroblastoma, especially when combined with the independent risk factor serum lactate dehydrogenase.

Clinical features, treatment strategies, and prognosis of epithelioid inflammatory myofibroblastic sarcoma in children: a multicenter experience.

Background: Inflammatory myofibroblastic tumors (IMTs) are a spectrum of tumors that range in morphology and biological behavior from benign, intermediate, to apparently malignant and epithelioid inflammatory myofibroblastic sarcoma (EIMS) is one of the malignant subtypes. This study tried to provide experience and new ideas for treating this rare disease. Methods: This study retrospectively analyzed and followed up 12 children with EIMS admitted to Beijing Children's Hospital, Baoding Children's Hospital, and Children's Hospital of Chongqing Medical University from August 2016 to May 2022. Results: Of the 12 children, 7 were male and 5 were female, with a median age of 74.50 [interquartile range (IQR), 61.50-90.00] months. Of these patients, eight had a single lesion and four had multiple lesions. The maximum diameter of the single tumor foci was 19.30 cm, the full meridian of the multiple tumor foci target lesions was 32.67 cm, and the median maximum tumor size was 11.99 (IQR, 7.80-15.70) cm. The site of disease was the abdominopelvic cavity in eight cases, the thoracic cavity in two cases, the maxillofacial region in one case, and the larynx in one case. The clinical manifestations were predominantly elevated body temperature (n=8). There was one case of ROS1 fusion mutation and nine cases of ALK fusion mutation. Of the 12 children, 6 were biopsied at the initial diagnosis and 6 were surgically treated. Follow-up treatment included preoperative neoadjuvant chemotherapy (n=4), peritoneal thermal perfusion therapy (n=2), targeted therapy (n=3), postoperative chemotherapy (n=5), and radiotherapy (n=3). The follow-up time was 14.50 (IQR, 10.50-31.50) months, with eight cases of tumor-free survival, two cases of death, and two cases of loss of follow-up. Conclusions: EIMS in children is extremely rare and clinically aggressive. The clinical presentation is nonspecific, and the initial diagnosis of the tumor is often large. Mutations in the ALK gene are common in EIMS. Surgery is the mainstay of EIMS treatment, and patients benefit from a multidisciplinary combination that includes targeted therapies, with long-term prognosis remaining subject to ongoing follow-up.

Intratumoral CXCR4hi neutrophils display ferroptotic and immunosuppressive signatures in hepatoblastoma.

Pediatric hepatoblastoma (HB) is the most common primary liver malignancy in infants and children. With great diversity and plasticity, tumor-infiltrating neutrophils were one of the most determining factors for poor prognosis in many malignant tumors. In this study, through bulk RNA sequencing for sorted blood and tumor-infiltrated neutrophils and comparison of neutrophils in tumor and para-tumor tissue by single-cell sequencing, we found that intratumoral neutrophils were composed of heterogenous functional populations at different development stages. Our study showed that terminally differentiated neutrophils with active ferroptosis prevailed in tumor tissue, whereas, in para-tumor, pre-fate naïve neutrophils were dominant and ferroptotic neutrophils dispersed in a broad spectrum of cell maturation. Gene profiling and in vitro T-cell coculture experiment confirmed that one of main functional intratumoral neutrophils was mainly immunosuppressive, which relied on the activation of ferroptosis. Combining the bulk RNA-seq, scRNA-seq data, and immunochemistry staining of tumor samples, CXCL12/CXCR4 chemotaxis pathway was suggested to mediate the migration of neutrophils in tumors as CXCR4 highly expressed by intratumoral neutrophils and its ligand CXCL12 expressed much higher level in tumor than that in para-tumor. Moreover, our study pinpointed that infiltrated CXCR4hi neutrophils, regardless of their differential distribution of cell maturation status in HB tumor and para-tumor regions, were the genuine perpetrators for immune suppression. Our data characterized the ferroptosis-dependent immunosuppression energized by intratumoral CXCR4 expression neutrophils and suggest a potential cell target for cancer immunotherapies.

Visual conservation treatment dilemmas in neuroblastoma with bilateral blindness.

OBJECTIVE: To investigate the clinical features, treatment strategies, and prognosis of neuroblastoma with bilateral blindness. METHODS: The clinical data of five patients with bilateral blindness neuroblastoma admitted to Beijing Children's Hospital from April 2018 to September 2020 were retrospectively collected to summarize their clinical characteristics. RESULTS: All patients were female and the median age at presentation was 25 (23, 41) months. The median intervention time from the onset of symptoms of bilateral blindness to the start of treatment was 10 (10, 12) days. All five cases were staged as stage M and grouped as high risk. Four cases were MYCN gene amplification and one case was MYCN acquisition. Five children were treated according to a high-risk neuroblastoma treatment protocol. Four children did not recover their vision after treatment, and one case improved to have light perception. All patients were effectively followed up for a median of 20 (12, 31) months, with three deaths, one tumor-free survival, and one recurrent tumor-bearing survival. CONCLUSION: Neuroblastoma with bilateral blindness is rare in the clinic, mostly in children of young age, and is often associated with MYCN amplification and multiple metastases. Early hormone shock therapy and optic nerve decompression are beneficial for preserving the child's vision. A joint multi-disciplinary treatment may help in the formulation of treatment decisions. Achieving a balance between good visual preservation and survival within the short optic nerve neurotherapeutic window is extremely challenging.

A case series of clinical characteristics and prognosis of congenital hepatoblastoma in a single center.

INTRODUCTION AND IMPORTANCE: Congenital hepatoblastoma is an exceedingly rare neoplasm, predominantly documented as isolated instances, with contentious aspects surrounding its therapeutic approaches and prognostic implications. This study aims to comprehensively summarize and evaluate the management experience of congenital hepatoblastoma (CHB). CASE PRESENTATION: This cohort comprised five infants diagnosed with hepatoblastoma, confirmed through pathological examination, and with an onset of symptoms before 28 days of age. They were enrolled between November 2019 and May 2022. The treatment course they underwent has been summarized, and their prognosis has been subject to analysis. CLINICAL DISCUSSION: Distinguishing congenital hepatoblastoma from other medical conditions is typically necessary. Given the patient's tender age, the approach to treatment demands comprehensive assessment, particularly in cases involving unique tumor locations or substantial tumor sizes. The selection of treatment modalities, encompassing preoperative neoadjuvant chemotherapy and surgical techniques, becomes of paramount importance. Furthermore, determining the treatment's endpoint poses a notable challenge and often necessitates a comprehensive evaluation. CONCLUSION: For pediatric patients afflicted with CHB, the application of preoperative neoadjuvant chemotherapy mitigates surgical risks, while the incorporation of surgical procedures followed by postoperative chemotherapy significantly enhances the overall prognosis. Additionally, AFP-L3% levels may serve as a valuable adjunctive marker signifying the conclusion of treatment.

Renal preservation in high-risk retroperitoneal neuroblastoma: Impact on survival and local progression.

BACKGROUND: Retroperitoneal neuroblastomas predominantly encroach upon critical structures, complicating surgical intervention and yielding elevated rates of surgery-associated complications. The kidney and renal vasculature represent the organs most susceptible to retroperitoneal neuroblastoma infiltration. Prior investigations have revealed high nephrectomy incidence and a paucity of renal-preserving surgical approaches. METHODS: A retrospective analysis was undertaken, examining patients with retroperitoneal neuroblastoma who underwent surgical procedures from January 2018 to December 2019 at Beijing Children's Hospital. RESULTS: The study encompassed 225 patients, presenting a median age of 37 months. Concomitant nephrectomy and tumor excision were performed in 11 (4.9%) patients, while 214 (95.1%) patients successfully preserved their kidneys during surgery. Among the patients who retained their kidneys, 8 (3.5%) experienced renal atrophy postoperatively. Predominant rationales for simultaneous nephrectomy included tumor invasion into the renal hilum (n = 9), markedly diminished function of the affected kidney (n = 2), and ureteral infiltration (n = 1). Subsequent to a median follow-up duration of 43 months, the outcomes demonstrated no considerable divergence in overall survival (OS) and event-free survival (EFS) between the nephrectomy and renal-preserving cohorts among high-risk (HR) neuroblastoma patients. Among the eight HR children who underwent nephrectomy, four experienced local recurrence. The nephrectomy cohort exhibited a significantly elevated cumulative incidence of local progression (CILP) relative to the renal-preserving group. CONCLUSION: In high-risk retroperitoneal neuroblastoma patients, nephrectomy does not enhance CILP, EFS, or OS. The guiding surgical tenet involves preserving the kidney while striving for gross total resection of the primary neoplasm, barring instances of severe deterioration of the affected renal function.

A case report of chest wall desmoplastic small round cell tumor in children.

INTRODUCTION: Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma predominantly afflicting young males. CASE PRESENTATION: In this current report, a two-year-old boy was admitted to the hospital for the evaluation of a left chest wall mass. Imaging revealed the tumor's presence in the left chest, compressing lung tissue. Subsequently, histological analysis confirmed the DSRCT diagnosis following a biopsy. The patient underwent a comprehensive management strategy centered around surgery, successfully completing the entire treatment course without experiencing relapse during subsequent follow-up assessments. DISCUSSION: When chest wall tumors are inoperable upon initial diagnosis, a biopsy is essential to clarify the pathology and assist in the diagnostic process. If a patient is diagnosed with DRSCT and conventional chemotherapy fails with surgical resection still not feasible, timely adjustment of the chemotherapy regimen coupled with targeted drug administration can reduce the tumor, enable complete resection, and improve the overall prognosis. CONCLUSION: DSRCT is a rare malignancy associated with a generally poor prognosis. The administration of a combined treatment approach involving oral targeted medication (anlotinib), chemotherapy, radiotherapy, and aggressive surgical resection holds the potential to enhance the prognosis for pediatric patients with this condition.

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.

Pediatric adrenocortical carcinoma: clinical features and application of neoadjuvant chemotherapy.

OBJECTIVE: To summarize the clinical characteristics of children with adrenocortical carcinoma (ACC) and preliminarily explore the indications for and efficacy of neoadjuvant chemotherapy in certain patients. METHODS: The data of 49 children with adrenocortical tumors (ACT) in the past 15 years were retrospectively analyzed, and after pathology assessment using Weiss system grading, 40 children diagnosed with ACC were included. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and three-dimensional (3D) reconstruction of contrast-enhanced computed tomography data were used to evaluate the response to neoadjuvant chemotherapy. RESULTS: Forty patients (17 males, 23 females) with ACC were enrolled. Abnormal hormone levels were common in children with ACC (n = 31), and in terms of clinical presentation, sexual precocity was the most common (n = 14, 35.0%), followed by Cushing's syndrome (n = 12, 30.0%). Seven of 40 children received neoadjuvant chemotherapy due to a maximum lesion diameter greater than 10 cm (n = 4), invasion of surrounding tissues (n = 2), intravenous tumor thrombus (n = 2), and/or distant metastasis (n = 2); 2 patients achieved partial response, and 5 had stable disease according to the RECIST 1.1 standard. Furthermore, 3D tumor volume reconstruction was performed in 5 children before and after neoadjuvant chemotherapy. Tumor volumes were significantly reduced in all 5 children, with a median volume reduction of 270 (interquartile range, IQR 83, 293) (range: 49-413) ml. After surgery with/without chemotherapy, the 5-year overall survival rate for all children was 90.0% (95% CI-confidence interval 80.0-100.0%), and the 5-year event-free survival rate was 81.5% (95% CI 68.0-97.7%). CONCLUSION: In the diagnosis and treatment of pediatric ACC, a comprehensive endocrine evaluation is necessary to facilitate early diagnosis. Surgery and chemotherapy are important components of ACC treatment, and neoadjuvant chemotherapy should be considered for children with ACC who meet certain criteria, such as a large tumor, distant metastases, or poor general condition.

Clinical features and outcomes of infantile soft-tissue sarcoma: A multicenter retrospective study in Beijing.

Background: Soft-tissue sarcomas during infancy are rare and understudied. With no data on this specific condition, we performed a retrospective study of infant-onset sarcomas based on a multi-institutional cohort in Beijing, China, collected over the past decade. We reviewed infantile soft-tissue sarcomas' clinical characteristics, treatments, and outcomes. Materials and Methods: The patients with soft-tissue sarcoma diagnosed from 0 to 12 months in four primary children's hospitals in Beijing from January 2010 to December 2019 were evaluated. Results: Fifty-one patients were enrolled, including 31 males and 20 females. The median age at the diagnosis was five months (range, 0-12), and seven (13.7%) patients were diagnosed in the first month of their life. Histologically, twenty-five patients were diagnosed with rhabdomyosarcoma (RMS), six were diagnosed with extraosseous Ewing sarcoma (EES), and twenty were diagnosed with nonrhabdomyosarcoma soft-tissue sarcoma (NRSTS). The treatment principles and details of RMS focused on reference to the Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols. For EES and NRSTS, chemotherapy was prescribed according to children's oncology group protocols. The five-year EFS/OS rates of RMS were 26.4% ± 19.5%/56.2 ± 17.8%, the five-year EFS/OS rate of EES was 50% ± 20.4%, and the five-year EFS/OS of NRSTS was 85.2% ± 9.8%/100%. Conclusions: Infant-onset soft-tissue sarcoma is heterogeneous. The primary location of the abdominal or pelvic cavity of RMS and EWS was at a later stage and had a poorer prognosis. Multimodal therapy resulted in successful disease control for the majority of patients. Standardization of treatment protocols will facilitate care for such challenging conditions.

Evaluating the clinical efficacy and limitations of indocyanine green fluorescence-guided surgery in childhood hepatoblastoma: A retrospective study.

BACKGROUND: Indocyanine green (ICG) fluorescence guided surgery has been used to treat childhood hepatoblastoma (HB), but the advantages and disadvantages of this technique have not been fully discussed. The purpose of this study is to summarize the experience and to explore the clinical value of this technique for children with HB. METHODS: 45 children with HB who underwent ICG fluorescence guided surgery (n = 22) and general surgery (n = 23) in our center from January 2020 to December 2022 were enrolled retrospectively. RESULTS: All the liver tumors in the ICG group showed hyperfluorescence, including total and partial fluorescent types. With the help of ICG navigation, minimally invasive surgery was performed in 3 cases. 18.2 % of cases with tumors could not be accurately identified under white light, but could be identified by fluorescence imaging. The fluorescent cutting lines of 59.1 % of cases were consistent with the safe cutting lines. In 36.4 % of cases, the fluorescence boundary was not clear because of tumor necrosis. In 36.4 % of cases, the fluorescence could not be detected on the inner edge of the tumors because of the depth. A total of 29 ICG (+) suspicious lesions were found during the operations, of which 5 were true positive lesions. CONCLUSION: ICG fluorescence guided surgery is safe and feasible in children with HB. This technique is helpful for locating tumors, determining margin and finding small lesions with negative imaging, especially in minimally invasive surgery. However, preoperative chemotherapy, tumor necrosis, tumor depth, and ICG administration impact the effect of fluorescence imaging.

Integration of clinical characteristics and molecular signatures of the tumor microenvironment to predict the prognosis of neuroblastoma.

This study aimed to analyze the clinical characteristics, cell types, and molecular characteristics of the tumor microenvironment to better predict the prognosis of neuroblastoma (NB). The gene expression data and corresponding clinical information of 498 NB patients were obtained from the Gene Expression Omnibus (GEO: GSE62564) and ArrayExpress (accession: E-MTAB-8248). The relative cell abundances were estimated using single-sample gene set enrichment analysis (ssGSEA) with the R gene set variation analysis (GSVA) package. We performed Cox regression analyses to identify marker genes indicating cell subsets and combined these with prognostically relevant clinical factors to develop a new prognostic model. Data from the E-MTAB-8248 cohort verified the predictive accuracy of the prognostic model. Single-cell RNA-seq data were analyzed by using the R Seurat package. Multivariate survival analysis for each gene, using clinical characteristics as cofactors, identified 34 prognostic genes that showed a significant correlation with both event-free survival (EFS) and overall survival (OS) (log-rank test, P value < 0.05). The pathway enrichment analysis revealed that these prognostic genes were highly enriched in the marker genes of NB cells with mesenchymal features and protein translation. Ultimately, USP39, RPL8, IL1RAPL1, MAST4, CSRP2, ATP5E, International Neuroblastoma Staging System (INSS) stage, age, and MYCN status were selected to build an optimized Cox model for NB risk stratification. These samples were divided into two groups using the median of the risk score as a cutoff. The prognosis of samples in the poor prognosis group (PP) was significantly worse than that of samples in the good prognosis group (GP) (log-rank test, P value < 0.0001, median EFS: 640.5 vs. 2247 days, median OS: 1279.5 vs. 2519 days). The risk model was also regarded as a prognostic indicator independent of MYCN status, age, and stage. Finally, through scRNA-seq data, we found that as an important prognostic marker, USP39 might participate in the regulation of RNA splicing in NB. Our study established a multivariate Cox model based on gene signatures and clinical characteristics to better predict the prognosis of NB and revealed that mesenchymal signature genes of NB cells, especially USP39, were more abundant in patients with a poor prognosis than in those with a good prognosis. KEY MESSAGES: Our study established a multivariate Cox model based on gene signatures and clinical characteristics to better predict the prognosis of NB and revealed that mesenchymal signature genes of NB cells, especially USP39, were more abundant in patients with a poor prognosis than in those with a good prognosis. USP39, RPL8, IL1RAPL1, MAST4, CSRP2, ATP5E, International Neuroblastoma Staging System (INSS) stage, age, and MYCN status were selected to build an optimized Cox model for NB risk stratification. These samples were divided into two groups using the median of the risk score as a cutoff. The prognosis of samples in the poor prognosis group (PP) was significantly worse than that of samples in the good prognosis group (GP). Finally, through scRNA-seq data, we found that as an important prognostic marker, USP39 might participate in the regulation of RNA splicing in NB.

A multicenter prospective study on the management of hepatoblastoma in children: a report from the Chinese Children's Cancer Group.

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

Translational practice of fluorescence in situ hybridisation to identify neuroblastic tumours with TERT rearrangements.

Recently, telomerase reverse transcriptase (TERT) gene rearrangements have been identified in neuroblastoma (NB), the typical pathological type of neuroblastic tumours (NTs); however, the prevalence of TERT rearrangements in other types of NT remains unknown. This study aimed to develop a practical method for detecting TERT defects and to evaluate the clinical relevance of TERT rearrangements as a biomarker for NT prognosis. A TERT break-apart probe for fluorescence in situ hybridisation (FISH) was designed, optimised, and applied to assess the genomic status of TERT in Chinese children with NTs at the Beijing Children's Hospital from 2016 to 2019. Clinical, histological, and genetic characteristics of TERT-rearranged NTs were further addressed. Genomic TERT rearrangements could be effectively detected by FISH and were mutually exclusive with MYCN amplification. TERT rearrangements were identified in 6.0% (38/633) of NTs overall, but 12.4% (31/250) in high-risk patients. TERT rearrangements identified a subtype of aggressive NTs with the characteristics of Stage 3/4, high-risk category, over 18 months old, and presenting all histological subtypes of NB and ganglioneuroblastoma nodular. Moreover, TERT rearrangements were significantly associated with elevated TERT expression levels and decreased survival chances. Multivariable analysis confirmed that it was an independent prognostic marker for NTs. FISH is an easily applicable method for evaluating TERT defects, which define a subgroup of NTs with unfavourable prognosis. TERT rearrangements would contribute to characterising NT molecular signatures in clinical practice.