Diencephalic Syndrome Due to Optic Pathway Gliomas in Pediatric Patients: An Italian Multicenter Study

: Diencephalic syndrome (DS) is a rare pediatric condition associated with optic pathway gliomas (OPGs). Since they are slow-growing tumors, their diagnosis might be delayed, with consequences on long-term outcomes. We present a multicenter case series of nine children with DS associated with OPG, with the aim of providing relevant details about mortality and long-term sequelae. We retrospectively identified nine children (6 M) with DS (median age 14 months, range 3-26 months). Four patients had NF1-related OPGs. Children with NF1 were significantly older than sporadic cases (median (range) age in months: 21.2 (14-26) versus 10 (3-17); p = 0.015). Seven tumors were histologically confirmed as low-grade astrocytomas. All patients received upfront chemotherapy and nutritional support. Although no patient died, all of them experienced tumor progression within 5.67 years since diagnosis and were treated with several lines of chemotherapy and/or surgery. Long-term sequelae included visual, pituitary and neurological dysfunction. Despite an excellent overall survival, PFS rates are poor in OPGs with DS. These patients invariably present visual, neurological or endocrine sequelae. Therefore, functional outcomes and quality-of-life measures should be considered in prospective trials involving patients with OPGs, aiming to identify "high-risk" patients and to better individualize treatment

Extra-neural metastases in pediatric diffuse midline gliomas, H3 K27-altered: presentation of two cases and literature review

IntroductionPediatric diffuse midline gliomas (DMG), H3 K27- altered, are the most aggressive pediatric central nervous system (CNS) malignancies. Disease outcome is dismal with a median survival of less than one year. Extra-neural metastases are an unusual occurrence in DMG and have been rarely described.Methods and resultsHere, we report on two pediatric patients affected by DMG with extra-neural dissemination. Their clinical, imaging, and molecular characteristics are reported here. An 11-year-old male 5 months after the diagnosis of diffuse intrinsic pontine glioma (DIPG) developed metastatic osseous lesions confirmed with computed tomography (CT) guided biopsy of the left iliac bone. The patient died one month after the evidence of metastatic progression. Another 11-year-old female was diagnosed with a cerebellar H3K27- altered DMG. After six months, she developed diffuse sclerotic osseous lesions. A CT-guided biopsy of the right iliac bone was non-diagnostic. She further developed multifocal chest and abdominal lymphadenopathy and pleural effusions. Droplet digital polymerase chain reaction (ddPCR) on pleural effusion revealed the presence of H3.3A mutation (c.83A>T, p.K28M). The patient died 24 months after the diagnosis of DMG and 3 months after the evidence of metastatic pleural effusion.DiscussionExtra-neural metastasis of DMG is a rare event and no standard therapy exists. An accurate and early diagnosis is necessary in order to develop a personalized plan of treatment. Further research is needed to gain further insights into the molecular pathology of DMG, H3K27- altered and improve the quality of life and the final outcome of patients with this deadly disease

Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma

BACKGROUND: This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). METHODS: WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. RESULTS: From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5-year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. CONCLUSIONS: In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports

Genetical, Immunological and Clinical Aspects of Inflammatory Gastrointestinal Disorders in Chilhood

CONCLUSIONS This thesis aimed to define the genetical, immunological and clinical aspects of gastrointestinal inflammatory diseases in pediatrics, with attention to Inflammatory bowel disease (CD and UC) and to Eosinophilic Esophagitis (EoE). The following results were obtained and reported: 1) The characterization of mice with gut specific expression of Interleukin-12 (IL-12) family genes and their susceptibility to experimental colitis; 2) The role of Interleukin-23 receptor (IL-23R) Gene in Pediatric-Onset IBD and Genotype- Phenotype association in a pediatric population affected by IBD; 3) In order to find non invasive and offer the best therapeutical approach to patients affected by IBD we investigated the intestinal permeability test and we found that altered intestinal permeability study is predictive of early relapse in children with steroid responsive UC. 4) Then, we tried to obtain himmunoistochemical markers of small bowel inflammation in children with ulcerative colitis. We demonstrated that the density of CD25+ mononuclear cells is increase in jejunal mucosa of IBD patients, even in absence of gross endoscopic and histopathological abnormalities. 5) We also investigated the new terapeutical approach for IBD. We evaluated the effect of probiotics (VSL#3) on Induction and manteinance of remission in Children with Ulcerative colitis. 6) Finally, we riserve the last chapter of the thesis to EoE, an emerging disease in childhood: the EoE. We describe patients affected by celiac disease that also show the histological pattern of EoE. The unexpectedly high prevalence of CD in this EoE affected population and the probability of an association between gluten-induced disease and EoE prompted us to report these patients

Serious infectious events and ibuprofen administration in pediatrics: a narrative review in the era of COVID-19 pandemic

Despite its recognized efficacy and tolerability profile, during the last decade a rise of adverse events following ibuprofen administration in children has been reported, including a possible role in worsening the clinical course of infections. Our aim was to critically evaluate the safety of ibuprofen during the course of pediatric infectious disease in order to promote its appropriate use in children

Eosinophilic oesophagitis and coeliac disease: is there an association?

Aim To report a series of 17 children affected by eosinophilic oesophagitis. Six of them also received a diagnosis of coeliac disease. Methods Seventeen children with history of dyspeptic symptoms were investigated. Results Six patients (M/F:2/4; mean age +/- s.d.: 5.6 +/- 1.3 years, range: 4-7 years; Group A) affected by eosinophilic oesophagitis also received a diagnosis of coeliac disease. The other 11 children (M/F:10/1, mean age +/- s.d.:7.5 +/- 2.3 years, range: 4-10 years, Group B) were affected solely by eosinophilic oesophagitis. All children underwent a change in dietary regimen. Group A received a gluten-free diet. Group B attempted dietary restriction based on the allergy testing results. After 6 months follow-up, all patients in Group A showed a complete disappearance of symptoms and three of them, who underwent upper gastrointestinal endoscopy, showed histologic remission. Patients from Group B had moderate clinical improvement and in seven of them (64%) a repeated upper gastrointestinal endoscopy showed a statistically significant reduction in eosinophilic infiltration. Conclusions This is the first reported group of patients with an association between coeliac disease and eosinophilic oesophagitis. To date, it is not possible to exclude that in a subgroup of children with coeliac disease the oesophageal eosinophilic infiltration could be caused by coeliac disease itself