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In the original Article, Dr. Laura Fontana's name was missing from the author list. This has been corrected (Dr. Fontana's name and details have been added to the HTML, PDF and XML version of this Article).
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INTRODUCTION: The aims of the PROBIT trial (clinicaltrials.gov: NCT03131284) were to prevent overweight or obesity occurring at two years of life, and improve feeding patterns during infancy. METHODS: The trial compared 252 northern Italian newborns whose paediatricians offered their parents an educational programme from the child's birth to the age of two years (intervention arm) with 216 newborns whose parents did not undergo the programme (control arm). This sample size was 80% powerful to detect, with a 0.05 α error, a 40% lower prevalence of overweight/obesity and a 57% lower prevalence of obesity in the intervention arm. At each well visit, the parents of the children in the intervention arm were given oral and written information about protective behaviours, with particular emphasis on responsive feeding. Overweight and obesity at two years of age were, respectively, defined as a body mass index of more than the 85th and the 95th percentile in accordance with the WHO growth charts. The sample size had 80% power to detect a 40% lower prevalence of overweight/obesity and a 57% lower prevalence of obesity in the intervention arm. RESULTS: At the age of two years, the prevalence of obesity in the intervention arm was 35% lower than among the controls, but the difference was not statistically significant (8.7% vs. 13.4%; p = 0.10) There was no difference in the prevalence of overweight/obesity between the groups (26.8% vs. 28.3%; p = 0.49). At the age of three months, a higher proportion of the infants in the intervention group were fed on demand (93% vs. 80%, p < 0.001). CONCLUSIONS: The PROBIT trial failed to detect a significantly lower prevalence of obesity in the intervention arm, but did improve early feeding patterns. More powerful trials and meta-analyses are required to establish whether educating newborns' parents can decrease the prevalence of early obesity.
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Lactancia Materna/estadística & datos numéricos , Conducta Alimentaria/fisiología , Fórmulas Infantiles/estadística & datos numéricos , Padres/educación , Obesidad Infantil/prevención & control , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Promoción de la Salud , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Italia/epidemiología , Masculino , Padres/psicología , Educación del Paciente como Asunto , Obesidad Infantil/epidemiología , DesteteRESUMEN
BACKGROUND: Patients with low-grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutation (mut) and 1p19q codeletion (codel) have a median overall survival of longer than 10 years. The aim of this study is to assess the role of postsurgical treatments. SUBJECTS, MATERIALS, AND METHODS: We evaluated patients with LGGs with IDH mut and 1p19q codel; IDH1/2 was performed by immunohistochemistry and quantitative polymerase chain reaction. In all wild-type cases, we performed next-generation sequencing. 1p19 codel analysis was performed by fluorescence in situ hybridization. RESULTS: Among the 679 patients, 93 with LGGs with IDH mutation and 1p19q codel were included. Median follow-up (FU) was 96.1 months. Eighty-four patients (90.3%) were high risk according to Radiation Therapy Oncology Group criteria. After surgery, 50 patients (53.7%) received only FU, 17 (18.3%) chemotherapy (CT), and 26 (30.1%) radiotherapy (RT) with (RT + CT, 8 patients, 8.6%) or without (RT, 18 patients, 19.4%) chemotherapy. Median progression-free survival (mPFS) was 46.3 months, 50.8 months, 103.6 months, and 120.2 months in patients with FU alone, with CT alone, with RT alone, or with RT + CT, respectively. Median PFS was significantly longer in patients who received postsurgical treatment (79.5 months, 95% confidence interval [CI]: 66.4-92.7) than patients who received FU (46.3 months, 95% CI: 36.0-56.5). Moreover, mPFS was longer in patients who received RT (alone or in combination with CT, n = 26, 113.8 months, 95% CI: 57.2-170.5) than those who did not (n = 67, 47.3 months, 95% CI: 36.4-58.2). In particular, temozolomide alone did not improve PFS with respect to FU. CONCLUSION: RT with or without chemotherapy, but not temozolomide alone, could extend PFS in IDH mut 1p19q codel LGGs. IMPLICATIONS FOR PRACTICE: Low-grade gliomas with high-risk features, defined according to Radiation Therapy Oncology Group criteria, receive radiotherapy and/or chemotherapy as postsurgical treatments. Radiotherapy, however, has serious long-term effects (cognitive impairment), which are to be taken into account in these young patients. Moreover, low-grade gliomas with isocitrate dehydrogenase mutation and 1p19q codeletion (oligodendrogliomas) have an extremely long survival and a better prognosis. This study suggests that postsurgical treatments prolong the time before tumor progression in patients with good prognosis as well as those with oligodendroglioma. Moreover, temozolomide alone might not be effective in prolonging progression-free survival.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/terapia , Oligodendroglioma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/patología , Encéfalo/cirugía , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Quimioradioterapia Adyuvante/métodos , Quimioradioterapia Adyuvante/estadística & datos numéricos , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/estadística & datos numéricos , Cromosomas Humanos Par 1/genética , Femenino , Estudios de Seguimiento , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Oligodendroglioma/genética , Oligodendroglioma/mortalidad , Oligodendroglioma/patología , Supervivencia sin Progresión , Temozolomida/uso terapéuticoRESUMEN
AIM: To evaluate relevance of clinical and molecular factors in adult low-grade gliomas (LGG) and to correlate with survival. METHODS: We reviewed records from adult LGG patients from 1991 to 2015 who received surgery and had sufficient tissue to molecular biomarkers characterization. RESULTS: 213 consecutive LGG patients were included: 17.4% were low-risk, according to Radiation Therapy Oncology Group (RTOG) risk assessment. IDH 1/2 mutation, 1p/19q co-deletion, MGMT methylation were found in 93, 50.8 and 65.3% of patients. Median follow-up was 98.3 months. In univariate analysis, overall survival was influenced by extent of resection (p = 0.011), IDH mutation (p < 0.001), 1p/19q co-deletion (p = 0.015) and MGMT methylation (p = 0.013). In multivariate analysis, RTOG clinical risk (p = 0.006), IDH mutation (p < 0.001) and 1p/19q co-deletion (p = 0.035) correlated with overall survival. RTOG clinical risk (p = 0.006), IDH mutation (p < 0.001) and 1p/19q co-deletion (p = 0.035) correlated with overall survival. CONCLUSION: Both clinical and molecular factors are essential to determine prognosis and treatment strategies.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Glioma/genética , Glioma/mortalidad , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/terapia , Deleción Cromosómica , Cromosomas Humanos Par 1 , Estudios de Cohortes , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Femenino , Glioma/terapia , Humanos , Isocitrato Deshidrogenasa/genética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Procedimientos Neuroquirúrgicos , Pronóstico , Factores de Riesgo , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: MGMT methylation status represents a powerful prognostic factor in newly diagnosed glioblastoma (GBM). Recently, its role in recurrent tumors has also been suggested; however, few data investigating the stability of this biomarker during the clinical course of the disease are available. In this study, we evaluated the rate of change of MGMT methylation status between diagnosis and first recurrence in patients who received tumor resection for recurrent GBM. METHODS: We included patients who received temozolomide concurrent with and adjuvant to radiotherapy after diagnosis of GBM and had a second surgery performed at least 3 months after radiotherapy completion. Other eligibility criteria were age ≥18 years and Eastern Cooperative Oncology Group performance status 0-2. We evaluated the MGMT methylation status by methylation-specific polymerase chain reaction. RESULTS: From our institutional data warehouse, 295 patients with recurrent GBM who underwent second surgery were evaluated. MGMT methylation status at both first and second surgery was available for 108 patients. MGMT was methylated in both surgeries in 38 patients (35.2%), while it was unmethylated in 43 patients (39.8%). We found a significant concordance between the first and the second MGMT methylation assessments (K = 0.500, p < .001), MGMT methylation being stable in 75% of the cases. CONCLUSION: MGMT methylation presents relative stability during the clinical course of GBM. The Oncologist 2017;22:432-437 IMPLICATIONS FOR PRACTICE: MGMT methylation is a prognostic factor in newly diagnosed glioblastoma. In this study, we evaluated the rate of change of MGMT methylation during the clinical course of the disease, and we found a significant concordance between the first and the second MGMT methylation assessments, with MGMT methylation being stable in 75% of the cases. Thus, re-testing this biomarker at recurrence does not provide further information for clinicians. MGMT methylation at first surgery, extent of resection at second surgery, and time between first and second surgery are significantly correlated with overall survival. Age and extent of resection are correlated with post-progression survival.
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Metilación de ADN/genética , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Glioblastoma/genética , Pronóstico , Proteínas Supresoras de Tumor/genética , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/genética , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Glioblastoma/diagnóstico , Glioblastoma/patología , Glioblastoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Regiones Promotoras Genéticas , TemozolomidaRESUMEN
We report a case of epithelioid angiosarcoma of the abdominal aortic wall after endovascular treatment for abdominal aortic aneurysm (EVAR). A 60-year-old male, treated 7 years before with EVAR, presented with abdominal back pain, general fatigue, and fever. It was assumed to be a graft infection with periaortic tissue compatible with an inflammatory reaction. The endograft was therefore completely removed and a Dacron silver aorto-bisiliac graft was implanted. After a few days the patient worsened, the angio-computed tomography scan showed a progressive increase of the periaortic mass and numerous small nodules in the abdomen were also detected. The patient was again brought to surgery, an axillo-bifemoral bypass was performed, and the aorto-bisiliac graft was removed but the patient died after surgery. The histological examination showed an aortic epithelioid angiosarcoma with peritoneal metastasis.
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Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Células Epitelioides , Hemangiosarcoma/etiología , Neoplasias Vasculares/etiología , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/patología , Aorta Abdominal/cirugía , Aortografía/métodos , Biopsia , Prótesis Vascular , Implantación de Prótesis Vascular/instrumentación , Angiografía por Tomografía Computarizada , Remoción de Dispositivos , Progresión de la Enfermedad , Procedimientos Endovasculares/instrumentación , Células Epitelioides/patología , Resultado Fatal , Hemangiosarcoma/diagnóstico por imagen , Hemangiosarcoma/secundario , Hemangiosarcoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/secundario , Politetrafluoroetileno , Tomografía Computarizada por Tomografía de Emisión de Positrones , Diseño de Prótesis , Reoperación , Stents , Factores de Tiempo , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Vasculares/patología , Neoplasias Vasculares/cirugíaRESUMEN
BACKGROUND: The most appropriate management of recurrent glioblastoma is still controversial. In particular, the role of surgery at recurrence remains uncertain. PATIENTS & METHODS: From our Institutional data warehouse we analyzed 270 consecutive patients who received second surgery for recurrent glioblastoma, to assess survival after second surgery, and to evaluate prognostic factors. RESULTS: Complete resection was found in 128 (47.4%) and partial resection in 142 patients (52.6%). Median survival from second surgery was 11.4 months (95% CI: 10.0-12.7). Multivariate analysis showed that age (p = 0.001), MGMT methylation (p = 0.021) and extent of surgery (p < 0.001) are associated with better survival. CONCLUSION: A complete resection should be the goal for second resection and younger age and MGMT methylation status might be considered in the selection of patients.
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Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Glioblastoma/patología , Glioblastoma/cirugía , Adolescente , Adulto , Anciano , Biomarcadores de Tumor , Neoplasias Encefálicas/mortalidad , Terapia Combinada , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Manejo de la Enfermedad , Femenino , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Retratamiento , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Proteínas Supresoras de Tumor/genética , Adulto JovenRESUMEN
BACKGROUND: Treatment options for glioblastoma (GBM) at recurrence have limited efficacy. Re-surgery has been used for confirmation of recurrent disease and to provide relief of symptoms but the real impact on survival is unknown. PATIENTS AND METHODS: A retrospective analysis was performed for GBM patients followed between 01/2005 and 06/2010 at our Institution. RESULTS: Two hundred and thirty-two patients with recurrent GBM were evaluated. One hundred and two patients (44%) were treated with re-surgery followed by chemotherapy and 130 patients (56%) with chemotherapy alone. In multivariate analysis, no significant effect of re-surgery was found, with age (p=0.001), MGMT methylation (p=0.002) and PFS at 6 months (p=0.0001) being significant prognostic factors. CONCLUSION: Second surgery might have a limited impact in the clinical course of recurrent GBM patients.
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Neoplasias Encefálicas/cirugía , Glioblastoma/cirugía , Recurrencia Local de Neoplasia/cirugía , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Glioblastoma/mortalidad , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Reoperación , Estudios RetrospectivosRESUMEN
The chloride channel 2 (CLCN2) gene codes for a protein organized in N- and C-terminal regions with regulatory functions and a transmembrane region which forms the ring of the pore. Mutations in the gene have previously been described in patients with idiopathic familial epilepsy. In this study we looked for new isoforms of CLCN2 and we estimated expression levels by real time PCR in brain tissue containing epileptic foci. Samples used in this study were first analyzed and selected to exclude mutations in the coding region of the gene. Four isoforms (skipping exons 3, 16, 22 and 6/7) were identified and quantified by Real Time PCR and compared with total expression of the gene. Expression of the region common to all CLCN2 isoforms was 50% less in epilepsy-associated brain tissue than in controls. The ratio of the various isoforms was slightly greater in epileptic than control tissue. The greatest difference was recorded in the temporal lobe for the isoform with skipped exon 22. Analysis of these isoforms in brain tissue containing epileptic foci suggests that CLCN2 could be implicated in epilepsy, even in the absence of mutations.
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Encéfalo/metabolismo , Canales de Cloruro/genética , Epilepsia/metabolismo , Anciano , Anciano de 80 o más Años , Empalme Alternativo , Encéfalo/patología , Canales de Cloruro CLC-2 , Canales de Cloruro/biosíntesis , Epilepsia/genética , Epilepsia/patología , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , ARN Mensajero/análisis , ARN Mensajero/genéticaRESUMEN
Following our pilot clinical study of combined IL-2/HSV-TK gene therapy for recurrent glioblastoma multiforme (GBM), we extended the protocol to a larger population of patients and evaluated safety, feasibility, and biological activity of treatment. A total of 12 patients received intratumor injection of retroviral vector-producing cells (RVPCs), followed by intravenous ganciclovir (GCV). Treatment was well tolerated with only minor adverse events. Transduction of tumor cells was demonstrated in tumor biopsies. A marked and persistent increase of intratumor and plasma Th1 cytokine levels was demonstrated after RVPC injection. At magnetic resonance imaging evaluation, two patients had a partial response (including a patient showing disappearance of a distant noninjected tumor mass), four had a minor response, four had stable disease, and two had progressive disease. The 6- and 12-month progression-free survival rates were 47 and 14%, respectively. The 6- and 12-month overall survival rates were 58 and 25%, respectively. In conclusion, the results of our clinical protocol of gene therapy for recurrent GBM, based on combined delivery of a suicide and a cytokine gene, demonstrate that intratumor injection of RVPCs was safe, provided effective transduction of the therapeutic genes to target tumor cells, and activated a systemic cytokine cascade, with tumor responses in 50% of cases.
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Neoplasias Encefálicas/terapia , Genes Transgénicos Suicidas/genética , Terapia Genética/métodos , Glioblastoma/terapia , Interleucina-2/uso terapéutico , Simplexvirus , Timidina Quinasa/uso terapéutico , Adulto , Anciano , Citocinas/sangre , Citocinas/metabolismo , Cartilla de ADN , Femenino , Vectores Genéticos/genética , Vectores Genéticos/uso terapéutico , Humanos , Interleucina-2/metabolismo , Masculino , Persona de Mediana Edad , Virus de la Leucemia Murina de Moloney , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Timidina Quinasa/metabolismoRESUMEN
BACKGROUND: To the authors' knowledge, there is a scarcity of accurate data regarding the feasibility of standard chemotherapy with procarbazine, lomustine, and vincristine (PCV) in a homogeneous series of patients with primary anaplastic oligodendroglioma (AO) and oligoastrocytoma (AOA) that was recurrent after surgery and standard radiotherapy. The aim of the current study was to evaluate the overall response rate, toxicity, and time to progression (TTP) with the use of standard PCV in this setting. METHODS: Between November 1994 and September 2000, 37 patients were enrolled in the current study. Of these, 23 had AO (62%) and 14 had AOA (38%). All patients received standard PCV comprised of lomustine (110 mg/m2) on Day 1, procarbazine (60 mg/m2) on Days 8-21, and vincristine (1.4 mg/m2, maximum total 2 mg) on Days 8 and 29. Cycles were repeated every 6 weeks. RESULTS: There were 11 complete responses (CR; 29.7%) and 11 partial responses (PR; 29.7%) reported and 8 patients had stable disease (SD; 21.6%). The response rate was higher in patients with AO compared with patients with AOA (77.2% vs. 22.7%; P = 0. 02). The median TTP, which was 12.3 months overall, was 30.3 months in patients who achieved a CR, 19.1 months in patients who achieved a PR, and 6.1 months in patients with SD. The median TTP was 18.6 months in AO patients and 6.14 in AOA patients. There were no cases of severe toxicity reported although in 16 patients (43%) who were free of disease progression, PCV was discontinued because of toxicity or inadequate recovery after 2 weeks of delay. CONCLUSIONS: PCV chemotherapy was reported to achieved a high response rate and TTP but incurred a high risk of persistent toxicity.