Validation of an LC-MS/MS method for urinary homovanillic and vanillylmandelic ACIDS and application to the diagnosis of neuroblastoma.

Background: Urinary catecholamine metabolites are well-established biomarkers for neuroblastoma (NB). Homovanillic acid (HVA) and vanillylmandelic acid (VMA) are the most frequently measured metabolites within SIOPEN - Catecholamine Working Group laboratories. Here, we evaluated the performance of a new LC-MS/MS in vitro diagnostic (IVD) kit for HVA and VMA to facilitate inter-laboratory harmonization.

Pediatric Opsoclonus-Myoclonus-Ataxia Syndrome can Lead to Long-Term Neurological, Neuropsychological, and Cognitive Sequelae Associated with Cerebellar Atrophy.

To outline the long-term neuropsychological profile of a pediatric cohort with Opsoclonus-Myoclonus-Ataxia Syndrome (OMAS), and evaluate whether volumetric brain abnormalities correlate with clinical findings years after onset. Twelve patients diagnosed with OMAS between 2008 and 2020 (6 males, mean age 9.6 years, median follow-up 5.

Primary Lung Tumors in Children: Insights from a Single-Center Case Series.

: Primary lung tumors in pediatric patients are rare, predominantly malignant, and present diagnostic challenges due to symptom overlap with more common conditions such as inflammatory processes or asthma. Evidence-based approaches for managing these rare neoplasms in childhood are scarce. This retrospective study reports the experience of a pediatric referral center in diagnosing and treating these tumors.

In Infants with Neuroblastoma Standard Therapy Only Partially Reverts the Fecal Microbiome Dysbiosis Present at Diagnosis.

The fecal microbiomes of 15 infants with neuroblastoma (NB) at the onset of the disease and after standard-of-care therapy have been prospectively analyzed compared to those of age-matched healthy infants. By applying several algorithms to 16S sequencing, we found that the fecal microbiomes of infants with NB at onset were abundant in , including different descendants of After completing therapy, their abundance decreased to a level like that observed in healthy infants. In contrast, the that showed at the onset an abundance like that of healthy infants doubled their amount after treatment.

Detection of plasma circulating GD2 ganglioside in patients with neuroblastoma and age-matched healthy children. Diagnostic and prognostic evaluation.

Background: GD2 ganglioside, a known specific marker for neuroblastoma (NB), exists in different lipoforms, including C18 and C20, which are distinguished by the length of their fatty acid chains. C18 and C20 GD2 lipoforms can be simultaneously measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We evaluated the diagnostic and prognostic performance of circulating GD2 levels in children with NB.

Strategies to manage the adverse effects of immunotherapy with dinutuximab beta in neuroblastoma: an Italian experience and literature review.

Purpose: Patients with high-risk neuroblastoma (HR NB) frequently present with metastases in the bone marrow and bone. Approximately 15% of these patients are refractory to induction therapy, and 50% relapse. Dinutuximab beta is an anti-GD2 monoclonal antibody approved in Europe for maintenance therapy of pediatric patients with HR NB.

Measurement of 3-O-methyldopa from dried plasma microsamples by high-resolution mass spectrometry: A tool for the diagnosis of patients with high-risk neuroblastoma.

Background: Risk assessment at diagnosis is crucial for neuroblastoma (NB) in order to address patients at high-risk to the most timely and appropriate treatments. 3-O-methyldopa (3-OMD), a direct metabolite of L-Dopa, is a promising biomarker of NB at diagnosis able to stratify high-risk patients.

Methods: We show the development and validation of a method for measuring 3-OMD from dried plasma samples (DPS) and plasma using liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) on a Thermo Fisher Scientific Orbitrap Exploris 120.

Exploring the frontier in robotic pediatric cancer surgery: when to move forward and when to stop.

Purpose: In recent years, the use of robotic-assisted minimally invasive surgery in pediatric oncology has increased. Despite its benefits, its adoption remains limited. This single-center retrospective analysis examines technical nuances, indications, and surgical limitations to prevent complications.

The power of art and the powers of adolescents with cancer: Age-specific projects at Italian pediatric oncology centers.

This article describes the oncology programs developed in Italy for adolescents and young adults with cancer, with a specific focus on the local projects created in pediatric oncology centers. A common feature of such projects is the emphasis on creative and artistic activities and laboratories (involving music, photography, novel writing, fashion design, and so on) designed to give young patients innovative means of expression.This article highlights the amazing powers of adolescents involved in these projects: the power to produce beautiful things in a place that is not normally associated with the idea of beauty; the power to make their doctors smile and grasp the profound sense of life; the power to make hospitals become places for producing culture.

From the identification of actionable molecular targets to the generation of faithful neuroblastoma patient-derived preclinical models.

Background: Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Although the overall survival of patients with NB has improved in the last years, more than 50% of high-risk patients still undergo a relapse. Thus, in the era of precision/personalized medicine, the need for high-risk NB patient-specific therapies is urgent.

Reaching the target dose with one single I-mIBG administration in high-risk neuroblastoma: The determinant impact of the primary tumour.

Background: I-metaiodobenzylguanidine ( I-mIBG) effectiveness in children with metastasised neuroblastoma (NB) is linked to the effective dose absorbed by the target; a target of 4 Gy whole-body dose threshold has been proposed. Achieving this dose often requires administering I-mIBG twice back-to-back, which may cause haematological toxicity. In this study, we tried identifying the factors predicting the achievement of 4 Gy whole-body dose with a single radiopharmaceutical administration.

Whole-body magnetic resonance imaging for staging Langerhans cell histiocytosis in children and young adults.

Introduction: Radiographic skeletal survey (R-SS) is the standard imaging technique for the initial staging of Langerhans cell histiocytosis (LCH). Whole-body magnetic resonance imaging (WB-MRI) has been proposed as an effective, radiation-free alternative.

Methods: We prospectively assessed patients with LCH followed at three tertiary centers in Italy and Austria.

Strategies for Potentiating NK-Mediated Neuroblastoma Surveillance in Autologous or HLA-Haploidentical Hematopoietic Stem Cell Transplants.

High-risk neuroblastomas (HR-NB) still have an unacceptable 5-year overall survival despite the aggressive therapy. This includes standardized immunotherapy combining autologous hemopoietic stem cell transplantation (HSCT) and the anti-GD2 mAb. The treatment did not significantly change for more than one decade, apart from the abandonment of IL-2, which demonstrated unacceptable toxicity.

Nucleolin expression has prognostic value in neuroblastoma patients.

Background: Neuroblastoma (NB) represents the most frequent form of extra-cranial solid tumour of infants, responsible for 15% of childhood cancer deaths. Nucleolin (NCL) prognostic value in NB was investigated.

Methods: NCL protein expression was retrospectively evaluated in tumour samples of NB patients at diagnosis and after chemotherapy.

Suprarenal Masses in Very Young Infants: Is It Safe to Watch and Wait? Report of a SIOPEN Observational Study Results.

To assess whether expectant observation of infants ≤ 90 days old with small suprarenal masses (sSRMs) could avoid unnecessary surgery without impacting outcome. Infants ≤ 90 days with a ≤ 5 cm mass, without midline extension or lymph node or distant spread were registered (ClinicalTrials.org:NCT01728155).

Untargeted LC-HRMS Based-Plasma Metabolomics Reveals 3-O-Methyldopa as a New Biomarker of Poor Prognosis in High-Risk Neuroblastoma.

Neuroblastoma (NB) is the most common extracranial malignant tumor in children. Although the survival rate of NB has improved over the years, the outcome of NB still remains poor for over 30% of cases. A more accurate risk stratification remains a key point in the study of NB and the availability of novel prognostic biomarkers of "high-risk" at diagnosis could help improving patient stratification and predicting outcome.

Connectivity Map Analysis Indicates PI3K/Akt/mTOR Inhibitors as Potential Anti-Hypoxia Drugs in Neuroblastoma.

Neuroblastoma (NB) is one of the deadliest pediatric cancers, accounting for 15% of deaths in childhood. Hypoxia is a condition of low oxygen tension occurring in solid tumors and has an unfavorable prognostic factor for NB. In the present study, we aimed to identify novel promising drugs for NB treatment.

Cell surface Nucleolin represents a novel cellular target for neuroblastoma therapy.

Background: Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Nucleolin (NCL) is a protein overexpressed and partially localized on the cell surface of tumor cells of adult cancers. Little is known about NCL and pediatric tumors and nothing is reported about cell surface NCL and NB.

Multiparametric flow cytometry highlights B7-H3 as a novel diagnostic/therapeutic target in GD2neg/low neuroblastoma variants.

Background: High-risk neuroblastomas (HR-NBs) are rare, aggressive pediatric cancers characterized by resistance to therapy and relapse in more than 30% of cases, despite using an aggressive therapeutic protocol including targeting of GD2. The mechanisms responsible for therapy resistance are unclear and might include the presence of GD2neg/low NB variants and/or the expression of immune checkpoint ligands such as B7-H3.

Method: Here, we describe a multiparametric flow cytometry (MFC) combining the acquisition of 10 nucleated singlets, Syto16pos CD45neg CD56pos cells, and the analysis of GD2 and B7-H3 surface expression.

Malignant sacrococcygeal germ cell tumors in childhood: The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience.

Purpose: To evaluate clinical features at diagnosis, prognostic factors, and outcomes of malignant sacrococcygeal germ cell tumors (SC-GCTs) in patients enrolled in the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) TCG 2004 protocol.

Patients And Methods: A prospective analysis was conducted on all consecutive patients diagnosed with malignant SC-GCTs between January 2004 and May 2017. Patients with stage I underwent surgery and subsequent surveillance, the others received pediatric cisplatinum-etoposide-bleomycin (pPEB) regimen and eventual deferred surgery.

Resection of primary tumor in stage 4S neuroblastoma: a second study by the Italian Neuroblastoma Group.

Purpose: To clarify the role of primary tumor resection in stage 4S neuroblastoma.

Methods: We investigated a cohort of 172 infants diagnosed with stage 4S neuroblastoma between 1994 and 2013. Of 160 evaluable patients, 62 underwent upfront resection of the primary tumor and 98 did not.