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1.
BMC Cardiovasc Disord ; 21(1): 81, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563223

RESUMO

BACKGROUND: Myocardial iron overload in patients with thalassemia major (TM) is one of the most important complications. The purpose of the study was to identify advanced echocardiography parameters for early identification of myocardial dysfunction during follow-up of patients with TM. METHODS: Forty TM patients who were 41 ± 5 years old were included in the study and divided into two groups according to cardiac magnetic resonance T2* results (Group 1: Τ2* > 25 ms, Group 2: Τ2* ≤ 25 ms). Liver T2* parameters were also measured. Conventional and deformational echocardiographic parameters were measured at baseline and approximately 2 years later. RESULTS: Thirty-two patients had Τ2* = 34 ± 4 ms (Group 1), and 8 had Τ2* = 17 ± 9 ms (Group 2). Blood consumption was 185 ± 60 and 199 ± 37 ml/kg/yr (p = 0.64), and liver T2* was 4 ± 5 and 17 ± 21 ms (p = 0.01) in Groups 1 and 2, respectively. At baseline, Group 1 had better left ventricular global longitudinal strain (GLS) (- 22 ± 3 vs. - 18 ± 5, p = 0.01) and similar left ventricular ejection fraction (LVEF) (62 ± 5% vs. 58 ± 10%, p = 0.086) than Group 2. At the 28 ± 11-month follow-up, LVEF, GLS, and T2* values in Group 1 (63 ± 3%, - 21 ± 3%, 34 ± 4 ms) and Group 2 (56 ± 11%, - 17 ± 4%, 17 ± 9 ms) did not change significantly compared to their corresponding baseline values. In 8 patients from Group 1, a worsening (> 15%) in LS (p = 0.001) was detected during follow-up, with a marginal reduction in LVEF. CONCLUSIONS: GLS seems to be an efficient echocardiographic parameter for detecting hemochromatosis-related cardiac dysfunction earlier than LVEF. It also seems to be affected by other factors (free radical oxygen, immunogenetic mechanisms or viral infections) in a minority of patients, underscoring the multifactorial etiology of cardiomyopathy.

2.
N Engl J Med ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33283989

RESUMO

Transfusion-dependent ß-thalassemia (TDT) and sickle cell disease (SCD) are severe monogenic diseases with severe and potentially life-threatening manifestations. BCL11A is a transcription factor that represses γ-globin expression and fetal hemoglobin in erythroid cells. We performed electroporation of CD34+ hematopoietic stem and progenitor cells obtained from healthy donors, with CRISPR-Cas9 targeting the BCL11A erythroid-specific enhancer. Approximately 80% of the alleles at this locus were modified, with no evidence of off-target editing. After undergoing myeloablation, two patients - one with TDT and the other with SCD - received autologous CD34+ cells edited with CRISPR-Cas9 targeting the same BCL11A enhancer. More than a year later, both patients had high levels of allelic editing in bone marrow and blood, increases in fetal hemoglobin that were distributed pancellularly, transfusion independence, and (in the patient with SCD) elimination of vaso-occlusive episodes. (Funded by CRISPR Therapeutics and Vertex Pharmaceuticals; ClinicalTrials.gov numbers, NCT03655678 for CLIMB THAL-111 and NCT03745287 for CLIMB SCD-121.).

4.
Eur J Haematol ; 105(6): 692-703, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32886826

RESUMO

ß-thalassemia major is an inherited hemoglobinopathy that requires lifelong red blood cell transfusions and iron chelation therapy to prevent complications due to iron overload. Traditionally, ß-thalassemia has been more common in certain regions of the world such as the Mediterranean, Middle East, and Southeast Asia. However, the prevalence of ß-thalassemia is increasing in other regions, including Northern Europe and North America, primarily due to migration. This review summarizes the available data on the changing incidence and prevalence of ß-thalassemia as well as factors influencing disease frequency. The data suggest that the epidemiology of ß-thalassemia is changing: Migration has increased the prevalence of the disease in regions traditionally believed to have a low prevalence, while, at the same time, prevention and screening programs in endemic regions have reduced the number of affected individuals. Various approaches to prevention and screening have been used. Region-specific prevention and treatment programs, customized to align with local healthcare resources and cultural values, have been effective in identifying patients and carriers and providing information and care. Significant challenges remain in universally implementing these programs.

6.
In Vivo ; 34(5): 2947-2954, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871837

RESUMO

BACKGROUND/AIM: Undifferentiated round cell sarcomas are a heterogeneous group of sarcomas. Identification of BCOR alterations, such as BCOR/CCNB3 and BCOR/MAML3 fusion genes and BCOR ITD has recently contributed in the precise diagnosis of these neoplasms, defining a new entity of the current classification of soft tissue and bone sarcomas. BCOR sarcomas share both morphological and genetic characteristics distinct from Ewing sarcomas. The scope of our study was to retrospectively identify BCOR sarcomas and find the correlations with the clinical outcome of these patients. PATIENTS AND METHODS: Histopathology and immunohistochemistry of pediatric tumor samples were combined with molecular testing (PCR) and fluorescent in situ hybridization to find BCOR sarcomas. RESULTS: We, herein, present our experience with BCOR sarcomas in a referral center of Greece. Moreover, we report in one case the detection of a variant BCOR/CCNB3 fusion not previously described. CONCLUSION: We are the first to report a splice variant of BCOR/CCNB3 which reveals the central position of BCOR in the oncogenesis of these tumors, furthermore we highlight the importance of molecular diagnostics in Ewing-like sarcomas and discuss the current treatment options for this rare entity.

7.
Exp Hematol Oncol ; 9: 20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793403

RESUMO

Background: Despite the proven benefits of iron chelation therapy (ICT) in the management of chronic iron overload and related complications, compliance to long-term ICT is challenging. Results from the ECLIPSE study, an open-label, randomized, multicenter, 2-arm, phase 2 study evaluated the safety of deferasirox dispersible tablet and film-coated tablet (FCT) formulations in patients with transfusion-dependent thalassemia (TDT) or very low, low, or intermediate risk myelodysplastic syndrome (MDS) treated over 24 weeks. Methods: The aim of the current study (a 2-year, open-label, multicenter, single-arm, phase 3 study) is to evaluate the long-term safety and efficacy of deferasirox FCT in a subset of patients with TDT or lower/intermediate-risk MDS treated for 2 years after the completion of 24 weeks of treatment with deferasirox in the ECLIPSE phase 2 study. Results: Of 53 patients enrolled, 34 (64.2%) completed treatment and study. Adverse events (AEs) reported in most patients (~ 70%) were of mild to moderate severity. Headache and diarrhea were the most frequently (> 25%) reported AEs. None of the serious AEs (including 1 death) were considered treatment related. No new safety signal was identified, and long-term safety of deferasirox FCT was consistent with the known safety profile of deferasirox. No major concerns associated with gastrointestinal tolerability, renal safety, or hematological abnormalities (thrombocytopenia/neutropenia) were reported during the 2 years. Patients receiving deferasirox FCT had a treatment compliance (by pill count) of ~ 90% and persistence (continuous use for ≥ 30 days) of > 95%. Reduction in serum ferritin level was almost consistent starting from week 2 across all post-baseline time points (relative reduction: month 6, 19%; month 12, 29%). Conclusions: The results from this 2-year interventional study suggest that the recommended dosing of deferasirox FCT, with better tolerability, palatability, and compliance, offers a favorable option of ICT for long-term management of iron overload and associated complications in TDT.Trial registration ClinicalTrials.gov, NCT02720536. Registered 28 March 2016, https://www.clinicaltrials.gov/ct2/show/NCT02720536.

8.
Palliat Support Care ; : 1-16, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32613930

RESUMO

OBJECTIVE: Psychosocial interventions in families of children with cancer are considered an effective way of empowering family members to tackle the complex hurdles they face. The ability of parents to develop adaptive coping strategies during the child's treatment is not only important to their own mental and physical health, but also to their child's well-being and long-term adjustment with the disease. METHODS: The aim of this review was to evaluate the existing literature for the period from 2009 to 2017 on psychosocial interventions targeting families of children with cancer. We searched the PubMed database using the following combination of keywords: "cancer AND children AND (intervention OR training) AND (mothers OR primary caregivers OR parents OR fathers OR siblings)." RESULTS: After careful evaluation of 995 papers, 17 full-text papers were found to match our criteria (12 randomized controlled trials and 5 quasi-experimental studies). The quality of the studies was assessed using the Delphi score questionnaire, and the score of the reviewed studies ranged from 3 to 5. The findings suggest that most interventions reduced distress and improved coping strategies among participants. Interventions, mainly cognitive behavioral therapy and problem-solving skills training targeting maternal distress, were associated with improved adjustment outcomes in mothers of children with cancer. SIGNIFICANCE OF RESULTS: Psychosocial interventions are helpful, and efforts should be made to promote them in a larger scale. Protocols should be implemented to ensure that all parents benefit. Computer-assisted methods may provide additional benefit by improving cancer-related knowledge and cancer-related communication.

10.
Lancet Haematol ; 7(6): e469-e478, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32470438

RESUMO

BACKGROUND: Transfusion-dependent haemoglobinopathies require lifelong iron chelation therapy with one of the three iron chelators (deferiprone, deferasirox, or deferoxamine). Deferasirox and deferiprone are the only two oral chelators used in adult patients with transfusion-dependent haemoglobinopathies. To our knowledge, there are no randomised clinical trials comparing deferiprone, a less expensive iron chelator, with deferasirox in paediatric patients. We aimed to show the non-inferiority of deferiprone versus deferasirox. METHODS: DEEP-2 was a phase 3, multicentre, randomised trial in paediatric patients (aged 1 month to 18 years) with transfusion-dependent haemoglobinopathies. The study was done in 21 research hospitals and universities in Italy, Egypt, Greece, Albania, Cyprus, Tunisia, and the UK. Participants were receiving at least 150 mL/kg per year of red blood cells for the past 2 years at the time of enrolment, and were receiving deferoxamine (<100 mg/kg per day) or deferasirox (<40 mg/kg per day; deferasirox is not registered for use in children aged <2 years so only deferoxamine was being used in these patients). Any previous chelation treatment was permitted with a 7-day washout period. Patients were randomly assigned 1:1 to receive orally administered daily deferiprone (75-100 mg/kg per day) or daily deferasirox (20-40 mg/kg per day) administered as dispersible tablets, both with dose adjustment for 12 months, stratified by age (<10 years and ≥10 years) and balanced by country. The primary efficacy endpoint was based on predefined success criteria for changes in serum ferritin concentration (all patients) and cardiac MRI T2-star (T2*; patients aged >10 years) to show non-inferiority of deferiprone versus deferasirox in the per-protocol population, defined as all randomly assigned patients who received the study drugs and had available data for both variables at baseline and after 1 year of treatment, without major protocol violations. Non-inferiority was based on the two-sided 95% CI of the difference in the proportion of patients with treatment success between the two groups and was shown if the lower limit of the two-sided 95% CI was greater than -12·5%. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with EudraCT, 2012-000353-31, and ClinicalTrials.gov, NCT01825512. FINDINGS: 435 patients were enrolled between March 17, 2014, and June 16, 2016, 393 of whom were randomly assigned to a treatment group (194 to the deferiprone group; 199 to the deferasirox group). 352 (90%) of 390 patients had ß-thalassaemia major, 27 (7%) had sickle cell disease, five (1%) had thalassodrepanocytosis, and six (2%) had other haemoglobinopathies. Median follow-up was 379 days (IQR 294-392) for deferiprone and 381 days (350-392) for deferasirox. Non-inferiority of deferiprone versus deferasirox was established (treatment success in 69 [55·2%] of 125 patients assigned deferiprone with primary composite efficacy endpoint data available at baseline and 1 year vs 80 [54·8%] of 146 assigned deferasirox, difference 0·4%; 95% CI -11·9 to 12·6). No significant difference between the groups was shown in the occurrence of serious and drug-related adverse events. Three (2%) cases of reversible agranulocytosis occurred in the 193 patients in the safety analysis in the deferiprone group and two (1%) cases of reversible renal and urinary disorders (one case of each) occurred in the 197 patients in the deferasirox group. Compliance was similar between treatment groups: 183 (95%) of 193 patients in the deferiprone group versus 192 (97%) of 197 patients in the deferisirox group. INTERPRETATION: In paediatric patients with transfusion-dependent haemoglobinopathies, deferiprone was effective and safe in inducing control of iron overload during 12 months of treatment. Considering the need for availability of more chelation treatments in paediatric populations, deferiprone offers a valuable treatment option for this age group. FUNDING: EU Seventh Framework Programme.


Assuntos
Deferasirox/uso terapêutico , Deferiprona/uso terapêutico , Transfusão de Eritrócitos/métodos , Hemoglobinopatias/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Administração Oral , Adolescente , Agranulocitose/induzido quimicamente , Agranulocitose/epidemiologia , Albânia/epidemiologia , Anemia Falciforme/terapia , Técnicas de Imagem Cardíaca/métodos , Criança , Pré-Escolar , Chipre/epidemiologia , Deferasirox/administração & dosagem , Deferasirox/economia , Deferiprona/administração & dosagem , Deferiprona/economia , Egito/epidemiologia , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Ferritinas/sangue , Ferritinas/efeitos dos fármacos , Grécia/epidemiologia , Hemoglobinopatias/terapia , Humanos , Lactente , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/economia , Sobrecarga de Ferro/sangue , Itália/epidemiologia , Imagem por Ressonância Magnética , Masculino , Cooperação do Paciente , Resultado do Tratamento , Tunísia/epidemiologia , Reino Unido/epidemiologia , Doenças Urológicas/induzido quimicamente , Doenças Urológicas/epidemiologia , Talassemia beta/terapia
11.
Haematologica ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32241839

RESUMO

Diamond Blackfan anemia (DBA) is predominantly an autosomal dominant inherited red cell aplasia primarily caused by pathogenic germline variants in ribosomal protein genes. DBA due to pathogenic RPL35A variants has been associated with large 3q29 deletions and phenotypes not common in DBA. We conducted a multi-institutional genotype-phenotype study of 45 patients with DBA associated with pathogenic RPL35A germline variants and curated the variant data on 21 additional cases from the literature. Genotype-phenotype analyses were conducted comparing patients with large deletions versus all other pathogenic variants in RPL35A. Twenty-two of the 45 cases had large deletions in RPL35A. After adjusting for multiple tests, a statistically significant association was observed between patients with a large deletion and steroid-resistant anemia, neutropenia, craniofacial abnormalities, chronic gastrointestinal problems, and intellectual disabilities (p<0.01) compared with all other pathogenic variants. Non-large deletion pathogenic variants were spread across RPL35A with no apparent hot spot and 56% of the individual family variants were observed more than once. In this, the largest known study of DBA patients with pathogenic RPL35A variants, we determined that patients with large deletions have a more severe phenotype that is clinically different from those with non-large deletion variants. Genes of interest also deleted in the 3q29 region that could be associated with some of these phenotypic features include LMLN and IQCG. Management of DBA due to large RPL35A deletions may be challenging due to complex problems and require comprehensive assessments by multiple specialists including immunologic, gastrointestinal, and developmental evaluations to provide optimal multidisciplinary care.

12.
Br J Haematol ; 190(1): 14-15, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32118286
13.
N Engl J Med ; 382(13): 1219-1231, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32212518

RESUMO

BACKGROUND: Patients with transfusion-dependent ß-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor ß superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent ß-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS: A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 µg per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS: The percentage of patients with transfusion-dependent ß-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.).


Assuntos
Receptores de Activinas Tipo II/uso terapêutico , Transfusão de Eritrócitos/estatística & dados numéricos , Hematínicos/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Talassemia beta/tratamento farmacológico , Receptores de Activinas Tipo II/efeitos adversos , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Ferritinas/sangue , Hematínicos/efeitos adversos , Humanos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Análise de Intenção de Tratamento , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Razão de Chances , Proteínas Recombinantes de Fusão/efeitos adversos , Esplenectomia , Adulto Jovem , Talassemia beta/genética , Talassemia beta/cirurgia , Talassemia beta/terapia
14.
Artigo em Inglês | MEDLINE | ID: mdl-32118814

RESUMO

BACKGROUND: Diamond-Blackfan anemia is a rare inherited bone marrow failure disease. Typical findings include hypoplastic macrocytic anemia, congenital anomalies, and a predisposition to cancer. The molecular basis of the disease is heterozygous mutations of ribosomal proteins without a strict correlation between genotype and phenotype. OBSERVATION: We present 2 cases of Diamond-Blackfan anemia diagnosed during infancy with interesting clinical, molecular, and family characteristics. CONCLUSIONS: A thorough evaluation of all family members is imperative to identify possible 'silent carriers' who are those with no physical stigmata and minor or absent hematological manifestations. New mutations could add in the map of the disease.

15.
Mediterr J Hematol Infect Dis ; 12(1): e2020006, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31934316

RESUMO

Due to the recent alarming increase in the incidence of hepatocellular carcinoma (HCC) in thalassemias, the present report reviews briefly the frequency, the major risk factors, and the surveillance of HCC in ß-thalassemias. Over the past 33 years, 153 cases of HCC were reported in patients with thalassemia, mainly in Italy and Greece. Among HCV-infected patients, additional factors promoting the development of HCC included: advanced age, male sex, chronic hepatitis B (CHB) co-infection, and iron overload. For early diagnosis of HCC, sequential ultrasound screening is recommended especially for thalassemia patients with chronic hepatitis C (CHC), which coincides with (one or more) additional risk factors for HCC. Here we report also the preliminary data from thalassemic patients, above the age of 30 years, followed in 13 ICET-A centers. The total number of enrolled patients was 1,327 (males: 624 and 703 females). The prevalence of HCC in thalassemia major patients [characterized by transfusion-dependency (TDT)] and thalassemia intermedia [characterized by nontransfusion dependency (NTDT)] was 1.66 % and 1.96 %, respectively. The lowest age at diagnosis of HCC was 36 years for TDT and 47 years for NTDT patients. We hope that this review can be used to develop more refined and prospective analyses of HCC magnitude and risk in patients with thalassemia and to define specific international guidelines to support clinicians for early diagnosis and treatment of HCC in thalassemic patients.

17.
Acta Biomed ; 90(3): 225-237, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31580308

RESUMO

BACKGROUND: More than five decades ago, thalassemia major (TDT) was fatal in the first decade of life. Survival and quality of life have improved progressively thanks to the implementation of a significant advance in diagnostic and therapeutic methods, consisting mainly of a frequent transfusion program combined with intensive chelation therapy. Improvement also includes imaging methods used to measure liver and cardiac iron overload. Improved survival has led to a growing number of adults requiring specialised care and counselling for specific life events, such as sexual maturity and acquisition of a family. AIMS OF THE STUDY: The main aim is to present the results of a survey on the marital and paternity status in a large population of adult males with TDT and NTDT living in countries with a high prevalence of thalassemia and a review of current literature using a systematic search for published studies. RESULTS: Ten out of 16 Thalassemia Centres (62.5%) of the ICET-A Network, treating a total of 966 male patients, aged above 18 years with ß- thalassemias (738 TDT and 228 NTDT), participated in the study. Of the 966 patients, 240 (24.8%) were married or lived with partners, and 726 (75.2%) unmarried. The mean age at marriage was 29.7 ± 0.3 years. Of 240 patients, 184 (76.6%) had children within the first two years of marriage (2.1 ± 0.1 years, median 2 years, range 1.8 - 2.3 years). The average number of children was 1.32 ± 0.06 (1.27 ± 0.07 in TDT patients and 1.47 ± 0.15 in NTDT patients; p: >0.05). Whatever the modality of conception, 184 patients (76.6%) had one or two children and 1 NTDT patient had 6 children. Nine (4.8%) births were twins. Of 184 patients, 150 (81.5%) had natural conception, 23 (12.5%) required induction of spermatogenesis with gonadotropins (hCG and hMG), 8 (4.3%) needed intracytoplasmic sperm injection (ICSI) and 3 adopted a child. 39 patients with TDT and NTDT asked for medical help as they were unable to father naturally: 7 TDT patients (17.9%) were azoospermic, 17 (37.7%) [13 with TDT and 4 with NTDT] had dysspermia and 15 (33.3%) [13 with TDT and 2 with NTDT] had other "general medical and non-medical conditions". CONCLUSIONS: Our study provides detailed information in a novel area where there are few contemporary data. Understanding the aspects of male reproductive health is important for physicians involved in the care of men with thalassemias to convey the message that prospects for fatherhood are potentially good due to progressive improvements in treatment regimens and supportive care.


Assuntos
Transfusão de Sangue , Estado Civil , Paternidade , Talassemia/terapia , Adulto , Comorbidade , Ferritinas/sangue , Humanos , Masculino , Talassemia/sangue
18.
Surg Neurol Int ; 10: 75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528413

RESUMO

Background: Hemangiopericytoma and solitary fibrous tumor (HPC/SFT) are considered to be one category according to the WHO 2016 classification of central nervous system tumors. HPC/SFT are subdivided into infantile (congenital) and adult type. Both are extremely rare entities, with little knowledge about etiology, prognosis, and optimal therapeutic strategy. Case Description: A 10-day-old girl was referred to our neurosurgical department due to hypotonia, palsy of the right oculomotor nerve, and prominent frontal fontanel. Imaging studies revealed a large occupying mass in the right middle cerebral fossa and the suprasellar cisterns. Only a subtotal resection of the tumor was possible, and postoperatively, she underwent chemotherapy (CHx). After a 3-year follow-up, the girl has minimum neurologic signs and receives no medications, and she can walk when she is supported. Conclusion: Congenital HPC/SFT is considered to have a benign behavior with a good prognosis. Treatment with gross total resection, when it is feasible, is the key to a good prognosis and low rates of recurrence. However, there is no consensus on the therapeutic strategy of a HPC/SFT, which is difficult to be completely resected. Literature lacks a therapeutic algorithm for these tumors, and thus, more clinical studies are needed to reach a consensus.

19.
J Neurooncol ; 145(1): 177-184, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31522324

RESUMO

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. METHODS: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. RESULTS: Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. CONCLUSION: This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/terapia , Glioma Pontino Intrínseco Difuso/diagnóstico , Glioma Pontino Intrínseco Difuso/terapia , Biópsia , Terapia Combinada , Progressão da Doença , Humanos , Prognóstico
20.
Postgrad Med ; 131(7): 445-452, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31443616

RESUMO

Given the complexity of neurocutaneous syndromes, a multidisciplinary approach has been advocated in order to provide optimum care. Subjects and Methods: Retrospective analysis of a cohort of 157 patients during a 3-year period, seen at a newly developed neurocutaneous clinic in a pediatric tertiary care hospital in Athens (Greece); and systematic chart review of the patients diagnosed with neurofibromatosis type 1 during this time period. Results: The most frequent neurocutaneous syndromes were neurofibromatosis type 1 (NF1) in 89 patients and tuberous sclerosis complex in 17. In 20.38% of patients a neurocutaneous syndrome was not confirmed. Approximately 2/3 of the NF1 patients underwent genetic analysis, and for 76.67% of them, a pathogenic mutation on the NF1 gene was revealed. Eighty-one patients manifested with generalized NF1 and eight with mosaic NF1. Dermatological manifestations included café-au-lait macules in all patients, followed by axillary and/or inguinal freckling (n = 57), external plexiform neurofibromas (n = 17), and cutaneous and subcutaneous neurofibromas (n = 11). Approximately half of patients had learning disabilities and attention deficit hyperactivity disorder, followed by mental retardation (n = 9), autistic spectrum disorders (n = 4), headaches (n = 3) and seizures (n = 2). Neuroimaging showed characteristic areas of hyperintensity on T2-weighted images in 74.07% of patients and optic pathway glioma in 19.75%. Two patients developed malignant peripheral sheath nerve tumor. Conclusions: Neurocutaneous syndromes are clinically heterogeneous and the surveillance of potential clinical complications is challenging. The availability of genetic diagnosis and novel imaging methods in this group of disorders is likely to further expand their clinical spectrum. Guidelines for assessment and management will need to be modified based on new available data.


Assuntos
Neurofibromatose 1/fisiopatologia , Equipe de Assistência ao Paciente , Esclerose Tuberosa/fisiopatologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Espectro Autista/complicações , Manchas Café com Leite/complicações , Criança , Pré-Escolar , Estudos de Coortes , Dermatologistas , Feminino , Genes da Neurofibromatose 1 , Testes Genéticos , Genética Médica , Grécia , Humanos , Lactente , Deficiência Intelectual/complicações , Deficiências da Aprendizagem/complicações , Masculino , Mosaicismo , Síndromes Neurocutâneas/genética , Síndromes Neurocutâneas/fisiopatologia , Síndromes Neurocutâneas/terapia , Neurofibroma Plexiforme/complicações , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Neurofibromatose 1/terapia , Neurologistas , Neuropsicologia , Oncologistas , Oftalmologistas , Cirurgiões Ortopédicos , Ambulatório Hospitalar , Pediatras , Radiologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/fisiopatologia , Neoplasias Cutâneas/terapia , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genética , Esclerose Tuberosa/terapia
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