Publications by authors named "Romanzo Antonino"

13 Publications

  • Page 1 of 1

Synchronous Presentation of Rare Brain Tumors in Von Hippel-Lindau Syndrome.

Diagnostics (Basel) 2021 May 31;11(6). Epub 2021 May 31.

Neuroradiology Unit, Department of Imaging, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.

Von Hippel-Lindau (VHL) disease is a heritable cancer syndrome in which benign and malignant tumors and/or cysts develop throughout the central nervous system (CNS) and visceral organs. The disease results from mutations in the VHL tumor suppressor gene located on chromosome 3 (3p25-26). A majority of individuals (60-80%) with VHL disease will develop CNS hemangioblastomas (HMG). Endolymphatic sac tumor (ELST) is an uncommon, locally aggressive tumor located in the medial and posterior petrosal bone region. Its diagnosis is based on clinical, radiological, and pathological correlation, and it can occur in the setting of VHL in up to 10-15% of individuals. We describe a 17-year-old male who presented with a chief complaint of hearing loss. Brain and spine Magnetic Resonance Imaging documented the presence of an expansive lesion in the left cerebellar hemisphere, compatible with HMG in association with a second cerebellopontine lesion compatible with ELST. The peculiarity of the reported case is due to the simultaneous presence of two typical characteristics of VHL, which led to performing comprehensive genetic testing, thus allowing for the diagnosis of VHL. Furthermore, ELST is rare before the fourth decade of life. Early detection of these tumors plays a key role in the optimal management of this condition.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
May 2021

Health-related quality of life in children at the diagnosis of Vernal Keratoconjunctivitis.

Pediatr Allergy Immunol 2021 Apr 20. Epub 2021 Apr 20.

Translational Specialized Pediatrics Research Area, Allergic Diseases Research Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

Background: Vernal keratoconjunctivitis (VKC) is a bilateral, chronic, allergic condition mostly affecting children. Clinical evaluations may not necessarily reflect the impact of the disease on the patients' health-related quality of life (HRQoL). We aimed to evaluate HRQoL in children at VKC diagnosis and to analyze correlations between HRQoL and clinical and laboratory variables.

Methods: We studied 5- to 12-year-old patients with VKC. Data on clinical history, instrumental eye evaluations, blood examinations, and visual analog scale (VAS) for the subjective symptoms were collected. HRQoL was assessed through a disease-specific validated Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) questionnaire.

Results: Seventy subjects were included in the analysis (female/male: 10/60; tarsal/mixed VKC form: 36/34). Clinical severity of VKC according to the Bonini scale was as follows: 14, mild; 36, moderate; and 20, severe. No significant difference was found concerning the distribution of patient age, gender, and history of allergic manifestations between tarsal and mixed VKC. A significant positive correlation was found between all QUICK scores and VAS scores, including different VAS subscale, while no significant correlation was found between QUICK scores and total sign scores, Schirmer's test, and corneal thickness. The presence of active severe VKC was not associated with worse HRQoL.

Conclusions: Our evidence shows that VKC patients experience impairment of HRQoL, especially in relation to the perception of symptoms independently of the ophthalmologic changes found, and that the QUICK questionnaire could be a useful tool to evaluate HRQoL in children with VKC, which may improve patients' classification and management.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
April 2021

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries.

Br J Ophthalmol 2020 Sep 15. Epub 2020 Sep 15.

Pediatric Oncology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

Background: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.

Methods: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.

Results: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease.

Conclusions: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
September 2020

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding.

Cancers (Basel) 2020 06 12;12(6). Epub 2020 Jun 12.

Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS, Ospedale Pediatrico Bambino Gesù, Piazza Sant'Onofrio 4, 00165 Rome, Italy.

Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Although recent advances in conservative treatment have greatly improved the visual outcome, local tumor control remains difficult in the presence of massive vitreous seeding. Traditional biopsy has long been considered unsafe in RB, due to the risk of extraocular spread. Thus, the identification of new biomarkers is crucial to design safer diagnostic and more effective therapeutic approaches. Exosomes, membrane-derived nanovesicles that are secreted abundantly by aggressive tumor cells and that can be isolated from several biological fluids, represent an interesting alternative for the detection of tumor-associated biomarkers. In this study, we defined the protein signature of exosomes released by RB tumors (RBT) and vitreous seeding (RBVS) primary cell lines by high resolution mass spectrometry. A total of 5666 proteins were identified. Among these, 5223 and 3637 were expressed in exosomes RBT and one RBVS group, respectively. Gene enrichment analysis of exclusively and differentially expressed proteins and network analysis identified in RBVS exosomes upregulated proteins specifically related to invasion and metastasis, such as proteins involved in extracellular matrix (ECM) remodeling and interaction, resistance to anoikis and the metabolism/catabolism of glucose and amino acids.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
June 2020

Global Retinoblastoma Presentation and Analysis by National Income Level.

JAMA Oncol 2020 05;6(5):685-695

Imam Hussein Cancer Center, Karbala, Iraq.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.

Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis.

Design, Setting, And Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017.

Main Outcomes And Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis.

Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]).

Conclusions And Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
May 2020

The impact of IGF-I, puberty and obesity on early retinopathy in children: a cross-sectional study.

Ital J Pediatr 2019 Apr 27;45(1):52. Epub 2019 Apr 27.

Unit of Endocrinology, "Bambino Gesù" Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.

Background: Childhood obesity has been correlated with coronary heart disease, but the correlation with microvascular disease remains unclear. The retinal microcirculation is affected early in the process of atherosclerosis and it offers the opportunity to indirectly study the effects of obesity on small brain vessels. Insulin-like growth factor 1 (IGF-I) is involved in angiogenesis and it has a crucial role in retinal vascularization.

Methods: A single-centre cross-sectional study was performed in 268 children and adolescents (116 males; mean age 13.03 ± 1.9 years,) with overweight/obesity, in order to identify risk factors for early retinopathy.

Results: Nine patients (3.3%) showed signs of retinopathy, defined as arteriovenous crossings and/or papilledema. Body mass index and fat mass, analysed by Dual X-ray Absorptiometry, were not different in patients with or without retinopathy. Patients with retinopathy were pubertal and showed higher waist circumference (107.78 ± 15.83 versus 99.46 ± 10.85 cm; p: 0.027), waist circumference/height ratio (0.66 ± 0.07 versus 0.62 ± 0.05; p: 0.04) and IGF-I SDS (0.03 ± 1.3 versus - 0.66 ± 0.9; p: 0.04). Multivariate analysis (after correction for sex, age, family history of type 2 diabetes mellitus, obesity, cardiovascular disease, hypertension and dyslipidaemia) showed that waist circumference/height ratio and IGF-I SDS were the only variables independently correlated with the presence of retinopathy.

Conclusions: Retinal vascular changes may become evident as an early complication of overweight and obesity, even during childhood and adolescence. Relatively high levels of IGF-I during this phase may act as an additional risk factor for microvascular damage. The screening for retinopathy should be proposed to all children and adolescents with overweight/obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
April 2019

Screening eye diseases in babies: an Italian experience on 5000 healthy, consecutive newborns.

Ann Ist Super Sanita 2015 ;51(4):387-9

UOC Neonatologia, Ospedale "Spirito Santo", Pescara, Italy.

Introduction: Visual performance of eyes with congenital pathologies is conditioned by an early diagnosis. Families having problems in accessing health services risk to delay or miss both an early diagnosis and an early treatment and amblyopia (lazy eye) prevention.

Methods: In our hospital, all full-term, healthy newborns are thoroughly examined by an ophthalmologist in the maternal ward, 1 to 3 days after birth.

Results: Among the first 5000 newborns examined, a high incidence of congenital pathologies compared to international literature was reported, with differences between Caucasians and non-Caucasians.

Conclusion: Performing an early in-hospital thorough eye examination in all newborns as a screening would be an effective way to miss none and to start an early and effective pathway of disease treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
February 2017

Advantages of a next generation sequencing targeted approach for the molecular diagnosis of retinoblastoma.

BMC Cancer 2015 Nov 4;15:841. Epub 2015 Nov 4.

Laboratory of Medical Genetics, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165, Rome, Italy.

Background: Retinoblastoma (RB) is the most common malignant childhood tumor of the eye and results from inactivation of both alleles of the RB1 gene. Nowadays RB genetic diagnosis requires classical chromosome investigations, Multiplex Ligation-dependent Probe Amplification analysis (MLPA) and Sanger sequencing. Nevertheless, these techniques show some limitations. We report our experience on a cohort of RB patients using a combined approach of Next-Generation Sequencing (NGS) and RB1 custom array-Comparative Genomic Hybridization (aCGH).

Methods: A total of 65 patients with retinoblastoma were studied: 29 cases of bilateral RB and 36 cases of unilateral RB. All patients were previously tested with conventional cytogenetics and MLPA techniques. Fifty-three samples were then analysed using NGS. Eleven cases were analysed by RB1 custom aCGH. One last case was studied only by classic cytogenetics. Finally, it has been tested, in a lab sensitivity assay, the capability of NGS to detect artificial mosaicism series in previously recognized samples prepared at 3 different mosaicism frequencies: 10, 5, 1 %.

Results: Of the 29 cases of bilateral RB, 28 resulted positive (96.5 %) to the genetic investigation: 22 point mutations and 6 genomic rearrangements (four intragenic and two macrodeletion). A novel germline intragenic duplication, from exon18 to exon 23, was identified in a proband with bilateral RB. Of the 36 available cases of unilateral RB, 8 patients resulted positive (22 %) to the genetic investigation: 3 patients showed point mutations while 5 carried large deletion. Finally, we successfully validated, in a lab sensitivity assay, the capability of NGS to accurately measure level of artificial mosaicism down to 1 %.

Conclusions: NGS and RB1-custom aCGH have demonstrated to be an effective combined approach in order to optimize the overall diagnostic procedures of RB. Custom aCGH is able to accurately detect genomic rearrangements allowing the characterization of their extension. NGS is extremely accurate in detecting single nucleotide variants, relatively simple to perform, cost savings and efficient and has confirmed a high sensitivity and accuracy in identifying low levels of artificial mosaicisms.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
November 2015

Sporadic Retinoblastoma and Pilocytic Astrocytoma: A Rare Association of Two Tumors.

Pediatr Blood Cancer 2015 Dec 14;62(12):2245-6. Epub 2015 Jul 14.

Department of Pediatric Hematology-Oncology and Stem Cell Transplantation.

View Article and Find Full Text PDF

Download full-text PDF

Source Listing
December 2015

Baseline central nervous system magnetic resonance imaging in early detection of trilateral retinoblastoma: pitfalls in the diagnosis of pineal gland lesions.

Anticancer Res 2014 Dec;34(12):7449-54

Department of Paediatric Haematology-Oncology and Stem Cell Transplantation, Bambino Gesù Children's Hospital, Rome, Italy.

Background: Trilateral retinoblastoma (TRB) is a rare disease associating bilateral retinoblastoma (RB) with primitive intracranial neuroblastic tumor.

Aim: To verify the occurrence of TRB in a single-Center case series and point out the clinical relevance of a baseline brain magnetic resonance imaging (MRI) in RB, focusing on pineal gland lesions.

Patients And Methods: Baseline MRI was routinely performed in all cases of RB from 1999. All MRIs were reviewed for this study and the RB database was checked in order to identify patients characteristics, treatments and follow-up.

Results: A total of 107 patients with RB were diagnosed between 1999 and 2012. Sixty-two patients had unilateral RB and 45 bilateral RB. MRI revealed the presence of pineal gland lesions in 10 patients (9%); seven were considered pineal benign cysts (6.5%), while in three patients (2.8%), TRB was suspected. All patients with TRB presented hereditary RB. In one patient, the suspected TRB was metachronous and in the other two patients was synchronous. Biopsy was not performed. Cerobrospinal fluid (CSF) was negative in all patients. The MRI modification, before treatment in the first case and later in the second case, confirmed the TRB diagnosis. The third patient died due to progressive Central Nervous System (CNS) disease that clearly confirmed the TRB diagnosis. None of the three patients had received prior chemotherapeutic treatment.

Discussion: TRB represents a rare condition in this series, occurring in three (2.8%) out of all patients with RB. A synchronous presentation with small lesion seems more frequent when a baseline MRI is performed. When a histologically-proven diagnosis is not available, a suspected diagnosis should be considered with caution and only follow-up will confirm the diagnosis. A wait-and-see approach should be considered.
View Article and Find Full Text PDF

Download full-text PDF

December 2014

Congenital cystic eye associated with a low-grade cerebellar lesion that spontaneously regressed.

BMC Ophthalmol 2014 Jun 17;14:80. Epub 2014 Jun 17.

Haematology-Oncology Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Background: Congenital cystic eye is an exceedingly rare ocular malformative disease, originated from the failure in the invagination of the optic vesicle during the fetal period and it can be associated with other ocular and non-ocular abnormalities. Diagnosis is based on clinical, radiological and histological features.

Case Presentation: We report a case of a congenital cystic eye associated with a cerebellar lesion accidentally detected at magnetic resonance imaging. Biopsy of the mass has not been performed due to parental rejection. Based on radiologic features and absence of clinical signs, a low-grade glioma diagnosis was hypothesized, but histological characterization was not obtained. Follow-up neuro-imaging 6 months after diagnosis showed that intracranial lesion spontaneously regressed without any treatment.

Conclusion: Our report stresses the importance of early MRI in children with ocular malformations, in order to detect associated intracranial defects, also of non-malformative origin. Additionally, we debate the clinic-radiological features of the intracranial lesions that could allow a wait-and-see policy. We also recommend a strict clinical and neuro-imaging follow-up for these lesions. Finally, biological mechanisms at the base of spontaneous regression of the brain lesions are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
June 2014

Two novel cases of trilateral retinoblastoma: genetics and review of the literature.

Cancer Genet 2013 Nov 19;206(11):398-401. Epub 2013 Nov 19.

Cytogenetics and Molecular Genetics Unit, Bambino Gesù Children's Hospital, Rome, Italy.

Retinoblastoma (RB) is the most common eye tumor in children; it originates from germline and/or somatic mutations that inactivate both alleles of the RB1 gene located on chromosome 13q14. Patients with unilateral or bilateral RB infrequently may develop an additional intracranial neuroblastic tumor, usually in the pineal gland, which characterizes the trilateral retinoblastoma (TRB) syndrome. The most common chromosomal abnormalities detected in TRB are deletions at 13q14, even if some rare cases of RB1 point mutations were described. In our report, we investigated two patients with TRB who showed a germline RB1 point mutation that has never been found to date and a large deletion involving RB1, respectively. Genetic data were compared to our in-house series and to current literature; these data suggested a role for other candidate regions in the pathogenesis of TRB. Moreover, our study highlights the need for new approaches allowing a multigenic analysis to clarify the genotype-phenotype correlation in TRB.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
November 2013