Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Int J Cancer ; 148(11): 2789-2798, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33428772

RESUMO

This retrospective observational study aimed to determine the effectiveness, safety and patterns of the use of nivolumab in patients with advanced melanoma in real-world clinical practice in France using data from a Temporary Authorization for Use Program (ATU). Data were collected from patients with unresectable or metastatic melanoma enrolled in a French national database (Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome: Ric-Mel) and treated with nivolumab during the ATU program (12 September 2014 to 31 August 2015). The primary objectives of the study were to evaluate the effect of patient characteristics on clinical response and overall survival (OS). Among 400 included patients (median age 66 years), the majority (83%) received nivolumab as second- or subsequent-line therapy. The median durations of progression-free survival and OS were 3.3 and 14.1 months, respectively, and 31.6% of patients achieved an objective response with a median duration of 20.1 months (range: 0-34.7). The safety profile of nivolumab was manageable and consistent with those of previous clinical trials, with an incidence of grade 3-5 adverse events of 13.8%. The safety and effectiveness of nivolumab in patients with advanced melanoma in real-world clinical practice in France were in line with the data reported in the Phase 3 trials CheckMate 066 and 037 of nivolumab in this patient population.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Melanoma/tratamento farmacológico , Nivolumabe/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Bases de Dados Factuais , França , Humanos , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
2.
Int J Mol Sci ; 22(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34281212

RESUMO

The individual response to ionizing radiation (IR) raises a number of medical, scientific, and societal issues. While the term "radiosensitivity" was used by the pioneers at the beginning of the 20st century to describe only the radiation-induced adverse tissue reactions related to cell death, a confusion emerged in the literature from the 1930s, as "radiosensitivity" was indifferently used to describe the toxic, cancerous, or aging effect of IR. In parallel, the predisposition to radiation-induced adverse tissue reactions (radiosensitivity), notably observed after radiotherapy appears to be caused by different mechanisms than those linked to predisposition to radiation-induced cancer (radiosusceptibility). This review aims to document these differences in order to better estimate the different radiation-induced risks. It reveals that there are very few syndromes associated with the loss of biological functions involved directly in DNA damage recognition and repair as their role is absolutely necessary for cell viability. By contrast, some cytoplasmic proteins whose functions are independent of genome surveillance may also act as phosphorylation substrates of the ATM protein to regulate the molecular response to IR. The role of the ATM protein may help classify the genetic syndromes associated with radiosensitivity and/or radiosusceptibility.


Assuntos
Neoplasias Induzidas por Radiação/etiologia , Tolerância a Radiação , Suscetibilidade a Doenças , Humanos
3.
Am J Dermatopathol ; 39(10): 764-766, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27779486

RESUMO

Necrotizing Infundibular Crystalline Folliculitis (NICF) is rare entity of unknown pathogenesis presenting as follicular crystalline papules arising in seborrheic areas. We report 2 cases of NICF in patients under targeted therapy for metastatic adenocarcinoma. In one case, the lesions reappeared cyclically every 3 weeks after each injection and in the other case, lesions persisted until disruption of the continuous oral therapy. Punch-biopsies demonstrated folliculitis with a plugging crystalline material associated with either bacteria or yeast. These are the first descriptions of drug-induced NICF.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/efeitos adversos , Toxidermias/etiologia , Foliculite/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Toxidermias/patologia , Cloridrato de Erlotinib/efeitos adversos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Neoplasias Pulmonares/tratamento farmacológico , Masculino
4.
BMC Health Serv Res ; 17(1): 542, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28789648

RESUMO

BACKGROUND: Management of metastatic melanoma is changing rapidly following the introduction of innovative effective therapies, with consequences for the allocation of healthcare resources. The objective of this study was to assess hospitalisation costs of metastatic melanoma in France from 2011 to 2013 from the perspective of the government payer. METHODS: The population studied corresponded to all adults with metastatic melanoma hospitalised in France between 1st January 2011 and 31st December 2013 who required chemotherapy, immunotherapy or radiotherapy due to tumour progression and unresectable Stage III or Stage IV melanoma. Metastatic melanoma was identified by ICD-10 codes documented in the hospital patient discharge records. For each patient, hospital stays were stratified into a pre- or post- progression health state using proxy variables for the RECIST criteria. All healthcare expenditure documented in the French national hospital claims system database and incurred between the index hospitalisation (or change of progression state) and the end of follow-up were analysed. For the principal analysis, valuation of healthcare resource consumption was performed using official national hospitalisation tariffs. Any expensive therapy administered during the stay was documented from a linked database of expensive drugs (FICHCOMP). RESULTS: Seventy-eight thousand seven hundred fifty hospital stays by 10,337 patients with metastatic melanoma were identified over the three-year study period. Annual per capita costs of hospitalisation were € 5046 in the pre-progression stage and € 19,006 in the post-progression stage. Hospitalisations attributed to adverse drug reactions to chemotherapy or immunotherapy were observed in 27% of patients. Annual per capita costs of these hospitalisations related to adverse drug reactions were € 3762 in the pre-progression stage and € 5523 in the post-progression stage. CONCLUSIONS: Hospitalisation costs related to metastatic melanoma rise substantially as the disease progresses. Treatment strategies which slow down disease progression would be expected to reduce costs of hospitalisation for metastatic melanoma, although they may also entail significant acquisition costs. This will entail organisational changes of resource allocation for the treatment of metastatic melanoma in hospitals.


Assuntos
Custos Hospitalares , Hospitalização/economia , Melanoma/economia , Adulto , Idoso , Bases de Dados Factuais , Tratamento Farmacológico/economia , Feminino , França/epidemiologia , Humanos , Imunoterapia/economia , Masculino , Melanoma/mortalidade , Melanoma/secundário , Melanoma/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos
6.
J Am Acad Dermatol ; 75(1): 113-125.e5, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27067394

RESUMO

BACKGROUND: The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study. OBJECTIVE: This report provides long-term follow-up data collected up to 12 months after the last patient was randomized. METHODS: In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review. RESULTS: Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively). LIMITATIONS: No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved. CONCLUSION: With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC.


Assuntos
Antineoplásicos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Piridinas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/efeitos adversos , Carcinoma Basocelular/secundário , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Neoplasias Cutâneas/patologia , Receptor Smoothened/antagonistas & inibidores , Taxa de Sobrevida , Adulto Jovem
7.
Lancet Oncol ; 16(6): 716-28, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25981810

RESUMO

BACKGROUND: Patients with advanced basal cell carcinoma have limited treatment options. Hedgehog pathway signalling is aberrantly activated in around 95% of tumours. We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma. METHODS: BOLT is an ongoing multicentre, randomised, double-blind, phase 2 trial. Eligible patients had locally advanced basal cell carcinoma not amenable to curative surgery or radiation or metastatic basal cell carcinoma. Patients were randomised via an automated system in a 1:2 ratio to receive 200 mg or 800 mg oral sonidegib daily, stratified by disease, histological subtype, and geographical region. The primary endpoint was the proportion of patients who achieved an objective response, assessed in the primary efficacy analysis population (patients with fully assessable locally advanced disease and all those with metastatic disease) with data collected up to 6 months after randomisation of the last patient. This trial is registered with ClinicalTrials.gov, number NCT01327053. FINDINGS: Between July 20, 2011, and Jan 10, 2013, we enrolled 230 patients, 79 in the 200 mg sonidegib group, and 151 in the 800 mg sonidegib group. Median follow-up was 13·9 months (IQR 10·1-17·3). In the primary efficacy analysis population, 20 (36%, 95% CI 24-50) of 55 patients receiving 200 mg sonidegib and 39 (34%, 25-43) of 116 receiving 800 mg sonidegib achieved an objective response. In the 200 mg sonidegib group, 18 (43%, 95% CI 28-59) patients who achieved an objective response, as assessed by central review, were noted among the 42 with locally advanced basal cell carcinoma and two (15%, 2-45) among the 13 with metastatic disease. In the 800 mg group, 35 (38%, 95% CI 28-48) of 93 patients with locally advanced disease had an objective response, as assessed by central review, as did four (17%, 5-39) of 23 with metastatic disease. Fewer adverse events leading to dose interruptions or reductions (25 [32%] of 79 patients vs 90 [60%] of 150) or treatment discontinuation (17 [22%] vs 54 [36%]) occurred in patients in the 200 mg group than in the 800 mg group. The most common grade 3-4 adverse events were raised creatine kinase (five [6%] in the 200 mg group vs 19 [13%] in the 800 mg group) and lipase concentration (four [5%] vs eight [5%]). Serious adverse events occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150 patients in the 800 mg group. INTERPRETATION: The benefit-to-risk profile of 200 mg sonidegib might offer a new treatment option for patients with advanced basal cell carcinoma, a population that is difficult to treat. FUNDING: Novartis Pharmaceuticals Corporation.


Assuntos
Compostos de Bifenilo/administração & dosagem , Carcinoma Basocelular/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Piridinas/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Bifenilo/efeitos adversos , Carcinoma Basocelular/patologia , Carcinoma Basocelular/radioterapia , Carcinoma Basocelular/cirurgia , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Piridinas/efeitos adversos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/cirurgia , Resultado do Tratamento
8.
Am J Dermatopathol ; 37(4): 299-304, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24999544

RESUMO

The authors describe a case of a 5 cm mixed desmoplastic melanoma occurring on the cheek of an 88-year-old white woman. The epidermis showed the features of lentigo maligna. Within the dermis, there was a mixed desmoplastic melanoma with 2 components. The first component consisted of infiltrative malignant spindled cells with prominent stromal fibrosis and had the typical appearance of desmoplastic melanoma. The second component was within the deep half of the tumor and consisted of a densely cellular nodule composed of spindled melanocytes admixed with many osteoclast-like giant cells. There was a peripheral neurotropism and tumor invaded bone. The Breslow thickness was 14 mm. On followup, a sacral metastasis was discovered, which had a similar morphology to the deep cellular nodule. Immunohistochemistry of spindled cells both inside and outside the nodule showed S100 positivity with the absence of other melanocytic markers (HMB-45, Melan-A). Smooth muscle actin and p63 were focally positive. The osteoclast-like giant cells expressed CD68 and MiTF. Array comparative genomic hybridization of the typical desmoplastic melanoma region had a flat profile, whereas the cellular osteoclast-like giant cell­rich region displayed important cytogenetic anomalies, some of which have been previously described in melanomas. The main array comparative genomic hybridization findings were confirmed by fluorescence in situ hybridization using specific probes. The differences in morphology and molecular cytogenetics between the 2 areas suggest that these might represent the progression or emergence of a more aggressive clone within the tumor. Subsequent metastatic spread to the bone may be a result of accumulated cytogenetic abnormalities.


Assuntos
Células Gigantes/patologia , Sarda Melanótica de Hutchinson/patologia , Melanoma/secundário , Osteoclastos/patologia , Sacro/patologia , Neoplasias Cutâneas/patologia , Neoplasias da Coluna Vertebral/secundário , Zigoma/patologia , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Diferenciação Celular , Bochecha , Hibridização Genômica Comparativa , Feminino , Células Gigantes/química , Humanos , Sarda Melanótica de Hutchinson/química , Sarda Melanótica de Hutchinson/genética , Sarda Melanótica de Hutchinson/cirurgia , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Melanoma/química , Melanoma/genética , Melanoma/cirurgia , Invasividade Neoplásica , Osteoclastos/química , Osteotomia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/cirurgia , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Zigoma/química , Zigoma/cirurgia
9.
Mol Neurobiol ; 59(1): 556-573, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34727321

RESUMO

Neurofibromatosis type 1 (NF1) is a disease characterized by high occurrence of benign and malignant brain tumours and caused by mutations of the neurofibromin protein. While there is an increasing evidence that NF1 is associated with radiosensitivity and radiosusceptibility, few studies have dealt with the molecular and cellular radiation response of cells from individuals with NF1. Here, we examined the ATM-dependent signalling and repair pathways of the DNA double-strand breaks (DSB), the key-damage induced by ionizing radiation, in skin fibroblast cell lines from 43 individuals with NF1. Ten minutes after X-rays irradiation, quiescent NF1 fibroblasts showed abnormally low rate of recognized DSB reflected by a low yield of nuclear foci formed by phosphorylated H2AX histones. Irradiated NF1 fibroblasts also presented a delayed radiation-induced nucleoshuttling of the ATM kinase (RIANS), potentially due to a specific binding of ATM to the mutated neurofibromin in cytoplasm. Lastly, NF1 fibroblasts showed abnormally high MRE11 nuclease activity suggesting a high genomic instability after irradiation. A combination of bisphosphonates and statins complemented these impairments by accelerating the RIANS, increasing the yield of recognized DSB and reducing genomic instability. Data from NF1 fibroblasts exposed to radiation in radiotherapy and CT scan conditions confirmed that NF1 belongs to the group of syndromes associated with radiosensitivity and radiosusceptibility.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Sobrevivência Celular/efeitos da radiação , Reparo do DNA/efeitos da radiação , Difosfonatos/farmacologia , Fibroblastos/efeitos da radiação , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Neurofibromatose 1/radioterapia , Radiação Ionizante , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Reparo do DNA/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Neurofibromatose 1/metabolismo
10.
Hum Mol Genet ; 18(15): 2768-78, 2009 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-19417008

RESUMO

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder which displays considerable inter- and intra-familial variability in phenotypic expression. To evaluate the genetic component of variable expressivity in NF1, we examined the phenotypic correlations between affected relatives in 750 NF1 patients from 275 multiplex families collected through the NF-France Network. Twelve NF1-related clinical features, including five quantitative traits (number of café-au-lait spots of small size and of large size, and number of cutaneous, subcutaneous and plexiform neurofibromas) and seven binary ones, were scored. All clinical features studied, with the exception of neoplasms, showed significant familial aggregation after adjusting for age and sex. For most of them, patterns of familial correlations indicated a strong genetic component with no apparent influence of the constitutional NF1 mutation. Heritability estimates of the five quantitative traits ranged from 0.26 to 0.62. Moreover, we investigated for the first time the role of the normal NF1 allele in the variable expression of NF1 through a family-based association study. Nine tag SNPs in NF1 were genotyped in 1132 individuals from 313 NF1 families. No significant deviations of transmission of any of the NF1 variants to affected offspring was found for any of the 12 clinical features examined, based on single marker or haplotype analysis. Taken together, our results provided evidence that genetic modifiers, unlinked to the NF1 locus, contribute to the variable expressivity of the disease.


Assuntos
Expressão Gênica , Neurofibromatose 1/genética , Neurofibromina 1/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , França , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Neurofibromatose 1/metabolismo , Neurofibromina 1/metabolismo , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , População Branca/genética
11.
Orphanet J Rare Dis ; 15(1): 37, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014052

RESUMO

Neurofibromatosis type 1 is a relatively common genetic disease, with a prevalence ranging between 1/3000 and 1/6000 people worldwide. The disease affects multiple systems with cutaneous, neurologic, and orthopedic as major manifestations which lead to significant morbidity or mortality. Indeed, NF1 patients are at an increased risk of malignancy and have a life expectancy about 10-15 years shorter than the general population. The mainstay of management of NF1 is a patient-centered longitudinal care with age-specific monitoring of clinical manifestations, aiming at the early recognition and symptomatic treatment of complications as they occur. Protocole national de diagnostic et de soins (PNDS) are mandatory French clinical practice guidelines for rare diseases required by the French national plan for rare diseases. Their purpose is to provide health care professionals with guidance regarding the optimal diagnostic and therapeutic management of patients affected with a rare disease; and thus, harmonizing their management nationwide. PNDS are usually developed through a critical literature review and a multidisciplinary expert consensus. The purpose of this article is to present the French guidelines on NF1, making them even more available to the international medical community. We further dwelled on the emerging new evidence that might have therapeutic potential or a strong impact on NF1 management in the coming feature. Given the complexity of the disease, the management of children and adults with NF1 entails the full complement healthcare providers and communication among the various specialties.


Assuntos
Neurofibromatose 1 , Adulto , Criança , Humanos , Neurofibromatose 1/diagnóstico , Pele
12.
Oncotarget ; 11(4): 378-385, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32064041

RESUMO

There is no standard of care for unresectable cutaneous squamous cell carcinoma (cSCC). Chemotherapy, alone or combined with radiotherapy, is commonly used mostly as palliative treatment; moreover, its poor safety profile limits its use most of the time, especially in elderly patients. Thus, alternative options are needed. Targeted molecular inhibitors, such as the epidermal growth factor receptor inhibitor cetuximab, seem promising, but data are limited. We retrospectively evaluated clinical outcomes of cetuximab as a single agent in this indication. The primary endpoint was the Disease Control Rate (DCR) at 6 weeks according to RECIST criteria. Secondary endpoints included DCR at 12 weeks, objective response rate (ORR) at 6 and 12 weeks, progression-free-survival (PFS), overall survival (OS), and safety profile. Fifty-eight patients received cetuximab as monotherapy. The median age was 83.2 (range, 47.4 to 96.1). The majority of patients was chemotherapy naïve. The median follow-up was 11.7 months (95% CI: 9.6-30.1). The DCR at 6 and 12 weeks was 87% and 70%, respectively. The ORR was 53% and 42%, respectively, at 6 and 12 weeks. The median PFS and OS were 9.7 months (95% CI: 4.8-43.4) and 17.5 months (95% CI: 9.4-43.1), respectively. Fifty-one patients (88%) experienced toxicity, and 67 adverse events related to cetuximab occurred. Most of them (84%) were grade 1 to 2. Our study shows that cetuximab is safe and efficient for the treatment of patients, even elderly ones, with advanced cSCC. These results indicate that cetuximab is a promising agent to test in new combinations, especially with immune checkpoint inhibitors such as anti-PD-1 agents.

13.
Wounds ; 20(6): 158-66, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25942521

RESUMO

UNLABELLED: Objective. Clinical interest of silver in the management of chronic wounds is not fully established. The main objective of this clinical study was to assess the ability of a new silver releasing lipido-colloid contact layer to promote the healing process of venous leg ulcers (VLU) presenting inflammatory signs suggesting a heavy bacteria colonization and then a delayed healing, in comparison to the same wound dressing not impregnated with silver salts. METHODS: This was an open-labeled, randomized, controlled trial. VLU presenting at least 3 out of 5 clinical signs suggesting heavy bacterial colonization were recruited. Patients were treated with contact layer silver dressing ([CLS], Restore® Contact Layer, Silver* (Hollister Wound Care, Libertyville, Ill) or contact layer dressing ([CL] Restore® Contact Layer**, Hollister Wound Care, Libertyville, Ill) for 4 weeks, then all treated ulcers were treated with CL for the 4 additional weeks. Wound evaluation and area measurements were conducted weekly during the first 4 weeks and then at week 6 and 8. Main efficacy criterion was absolute wound area decrease (AD) at week 4 and week 8. RESULTS: Patients (N = 102) were randomized and treated. Ulcers were present for nearly 11 months on average; 65% were recurrent and mean area was 20.0 ± 17.8 cm2. Almost 80% of the treated VLU were stagnating/aggravating with their previous treatment. By week 4, mean surface area decreased by 6.5 ± 13.4 cm2 (median: 4.2 cm2) and 1.3 ± 9.0 cm2 (median: 1.1 cm2) in CLS and CL groups, respectively (P = 0.023). At week 8, median decrease was 5.9 cm2 versus 0.8 cm2 (P = 0.002) with a wound percentage decrease of 47.9% and 5.6% (P = 0.036). Median closure rate was 0.145 versus 0.044 cm2/day (P = 0.009) at week 4 and remained higher in the CLS group up to week 8 even after switching to CL dressing in these patients (P = 0.001). Odds ratio (multinomial logistic regression) of the chance to reach a ≥ 40% wound area reduction was 2.7 (95% CI: 1.1 to 6.7; P = 0.038) for silver treated ulcers. Dressing tolerance was good in both groups. CONCLUSION: A 4-week treatment with silver releasing lipido-colloid contact layer promotes a sustained increase of closure rate of venous leg ulcers presenting inflammatory signs suggesting a high bacterial load. Also marketed as *Urgotul® Silver and **Urgotul®, Laboratoires Urgo, (France)..

14.
Nucl Med Commun ; 38(9): 771-779, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28704339

RESUMO

INTRODUCTION: Many studies have reported the high performance of 6-fluorine-18-fluorodihydroxyphenilalanine (F-FDOPA) PET/CT in the diagnosis of pheochromocytomas but nobody seems to have investigated physiological and pathological adrenal glands from a quantitative point of view. The purpose of the present study was to assess the quantitative F-FDOPA uptake of normal and pathologic adrenal glands and to establish thresholds to characterize pheochromocytomas. We were especially interested in characterizing the remaining adrenal glands captation after an adrenalectomy. PATIENTS AND METHODS: We reviewed 112 F-FDOPA PET/CT scans taken for different indications. A total of 212 adrenal glands, of which 17 were pheochromocytomas, were analyzed on the basis of their functional and morphological features. The final diagnosis was based on histologic proof when available (six pheochromocytomas) or after synthesis of clinical, biological, morphological, and functional results. Maximum standardized uptake value (SUVmax), mediastinum, and liver ratios in case of pheochromocytomas, adenomas, and solitary adrenal glands were determined and compared with those of healthy glands. Receiver operating characteristic curves were determined and areas under the curve were compared for different cutoffs of each index. RESULTS: Pheochromocytomas demonstrated a higher F-FDOPA uptake compared with normal adrenal glands (mean SUVmax: 7.5, SD 4.0, range: 3.5-20.0 vs. mean SUVmax: 2.6, SD: 0.8, range: 1.0-6.9) (P<0.0001). An SUVmax threshold of 4.2 has a sensitivity and specificity of 94 and 98%, respectively. The areas under the curve were 0.988, 0.991, and 0.987 for an SUVmax of 4.2, a mediastinum ratio of 3.0, and a liver ratio of 1.7, respectively. A large number of nonsecreting pheochromocytomas were noticed. On the basis of the SUVmax no statistically significant difference was found between secreting (SUVmax: 8.9, SD: 5.3) and nonsecreting pheochromocytomas (SUVmax: 5.1, SD: 0.9) (P=0.141). After unilateral adrenalectomy, solitary glands presented no increased uptake compared with healthy adrenal glands. An unexpected lower captation was also observed (SUVmax: 2.0, P=0.047). CONCLUSION: We confirm the high affinity of F-FDOPA for secreting or nonsecreting pheochromocytoma. Indeed within a series of various adrenal glands, only these tumors presented a significant increased uptake compared with normal adrenal glands. Because of a high rate of nonhypersecreting lesions, F-FDOPA can act as a surrogate to biological assays. After an adrenalectomy, the remaining glands did not demonstrate compensatory accumulation of F-FDOPA. To our knowledge this last point has never been addressed.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/metabolismo , Di-Hidroxifenilalanina/análogos & derivados , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/metabolismo , Feocromocitoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Adrenalectomia , Diagnóstico Diferencial , Di-Hidroxifenilalanina/farmacocinética , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Feocromocitoma/cirurgia , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Distribuição Tecidual , Resultado do Tratamento
15.
Clin Nucl Med ; 42(5): 379-382, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28319498

RESUMO

F-FDOPA is a well-established tool to explore pheochromocytomas. It tends to replace I-MIBG scan in metastatic pheochromocytomas, multiple endocrine neoplasia type 2-related tumors, succinate dehydrogenase [ubiquinone] iron-sulfur subunit-negative tumors, and succinate dehydrogenase[ZERO WIDTH SPACE]-positive lesions. To our knowledge, no study has characterized physiological and pathological adrenal glands with F-FDOPA from a quantitative point of view. We report the features of different normal and pathological adrenal glands with F-FDOPA. Within our series, only pheochromocytomas present a significantly increased uptake reflecting the high specificity of this tracer. Tumors such as adenomas or myelolipomas present no F-FDOPA significant accumulation. Interestingly, adrenal gland hyperplasia and solitary glands do not demonstrate compensatory uptake.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/diagnóstico por imagem , Di-Hidroxifenilalanina , Radioisótopos de Flúor , Feocromocitoma/diagnóstico por imagem , Compostos Radiofarmacêuticos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
16.
J Dermatolog Treat ; 17(2): 78-81, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16766330

RESUMO

BACKGROUND: Although the benefits of emollient therapy are widely accepted in atopic dermatitis, there is a relative lack of clinical evidence supporting their efficacy in these conditions. The aim of this study was to evaluate the efficacy, the tolerance and the effects on children's quality of life of a new moisturizer milk (Exomega milk) in childhood atopic dermatitis. METHODS: This controlled, randomized, multi-centric study had two parallel groups, involving children aged 6 months to 12 years, with mild and moderate atopic dermatitis (Scorad<35). The treated group applied the moisturizer milk twice a day for 2 months, in association with a cleansing bar. The non-treated group had only the cleansing bar. The use of strong and moderate topical corticoids was allowed and quantified. The following parameters were evaluated: Scorad, tolerance and the children's quality of life index. RESULTS: A total of 76 children (mean age 4 years) were included: 37 in the treated group, 39 in the non-treated group. After 2 months, the decrease of the Scorad index in the treated group was not statistically significant (p = 0.051) but detailed evaluation showed a significant improvement of xerosis (p = 0.01) and pruritus (p = 0.01) in the treated group compared with the non-treated group. Clinical improvement in the treated group after 2 months of treatment was correlated to a significant improvement of the children's quality of life index (p = 0.0011). Tolerance was good to excellent in 97% of cases. CONCLUSION: The milk emollient studied was found to provide an interesting auxiliary treatment in childhood atopic dermatitis since it gave positive results, in particular on xerosis and pruritus, as well as an improvement of the quality of life of the children.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Administração Cutânea , Criança , Pré-Escolar , Dermatite Atópica/patologia , Dermatite Atópica/psicologia , Fármacos Dermatológicos/administração & dosagem , Feminino , França , Humanos , Lactente , Masculino , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento
17.
Eur J Dermatol ; 26(3): 287-9, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26905513

RESUMO

Primary angiosarcoma of the breast is a rare malignant tumour that presents in young women as a painless mass or a sensation of fullness in the breast. To report two cases of primary breast angiosarcoma presenting with unusual and misleading cutaneous lesions. A clinical investigation including ultrasound, MRI and histological examination. In the first patient, the lesion appeared as a superficial, acquired angioma; in the second as an indolent superficial haematoma. This type of primary presentation is exceptional and the benign appearance of the lesion, combined with a lack of breast mass, is misleading. The benign appearance and the pathological aspect of these lesions can lead to misdiagnosis. Comparison of clinical and pathological data is necessary to prevent delay in diagnosis. We believe that all acquired angiomatous lesions developing on the breasts of young women should raise suspicion of angiosarcoma.


Assuntos
Neoplasias da Mama/diagnóstico , Hemangiossarcoma/diagnóstico , Neoplasias Cutâneas/secundário , Neoplasias da Mama/patologia , Feminino , Hemangiossarcoma/patologia , Hemangiossarcoma/secundário , Humanos , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Adulto Jovem
18.
Eur J Endocrinol ; 175(4): 335-44, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27450695

RESUMO

OBJECTIVE: Pheochromocytoma (PHEO) may occur in 0.1-5.7% of patients presenting with a neurofibromatosis type 1 (NF1). Current recommendations are to explore only symptomatic patients. The objective of the study is to evaluate the prevalence and the interest of a systematic PHEO screening in this population. DESIGN: A prospective study in a French tertiary center including consecutive NF1 patients older than 18 years. METHODS: A systematic screening combining abdominal imaging and urinary fractionated metanephrines was proposed. In case of positivity of one or both exams, (123)I-metaiodobenzylguanidine scintigraphy or [(18)F]-fluoro-dihydroxyphenylalanine PET imaging was performed. The diagnosis of secreting PHEO was retained in case of elevated urinary metanephrines associated with positive scintigraphy and non-secreting PHEO when urinary metanephrines were normal with a positive scintigraphy. RESULTS: Between January 2014 and August 2015, 234 patients were included and 156 patients (66.7%) completed both exams. In these 156 patients, 12 PHEOs were diagnosed, representing a prevalence of 7.7%. Of these, six PHEOs were secreting, with only two symptomatic patients. The tumor size of these PHEOs were bigger than that of non-secreting PHEO (25.2 ± 6.6 vs 14 ± 6.9 mm, P = 0.0165). One lesion was bilateral. Mean metanephrine and normetanephrine levels were 3.2 ± 2.6N and 2.8 ± 1N respectively. Three patients underwent surgery. The six patients with non-secreting PHEO were asymptomatic. One of them had bilateral lesion and one underwent surgery. CONCLUSIONS: PHEO in NF1, whether or not secreting, are mostly asymptomatic. The current strategy to explore only symptomatic patients leads to an underestimation of prevalence with the risks inherent to the existence of an unrecognized PHEO.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neurofibromatose 1/complicações , Feocromocitoma/diagnóstico por imagem , Adolescente , Neoplasias das Glândulas Suprarrenais/etiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/etiologia , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Adulto Jovem
19.
Int J Radiat Oncol Biol Phys ; 94(3): 450-60, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26867874

RESUMO

PURPOSE: Whereas post-radiation therapy overreactions (OR) represent a clinical and societal issue, there is still no consensual radiobiological endpoint to predict clinical radiosensitivity. Since 2003, skin biopsy specimens have been collected from patients treated by radiation therapy against different tumor localizations and showing a wide range of OR. Here, we aimed to establish quantitative links between radiobiological factors and OR severity grades that would be relevant to radioresistant and genetic hyperradiosensitive cases. METHODS AND MATERIALS: Immunofluorescence experiments were performed on a collection of skin fibroblasts from 12 radioresistant, 5 hyperradiosensitive, and 100 OR patients irradiated at 2 Gy. The numbers of micronuclei, γH2AX, and pATM foci that reflect different steps of DNA double-strand breaks (DSB) recognition and repair were assessed from 10 minutes to 24 hours after irradiation and plotted against the severity grades established by the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group. RESULTS: OR patients did not necessarily show a gross DSB repair defect but a systematic delay in the nucleoshuttling of the ATM protein required for complete DSB recognition. Among the radiobiological factors, the maximal number of pATM foci provided the best discrimination among OR patients and a significant correlation with each OR severity grade, independently of tumor localization and of the early or late nature of reactions. CONCLUSIONS: Our results are consistent with a general classification of human radiosensitivity based on 3 groups: radioresistance (group I); moderate radiosensitivity caused by delay of nucleoshuttling of ATM, which includes OR patients (group II); and hyperradiosensitivity caused by a gross DSB repair defect, which includes fatal cases (group III).


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Núcleo Celular/metabolismo , Quebras de DNA de Cadeia Dupla , Histonas/metabolismo , Lesões por Radiação/classificação , Tolerância a Radiação/fisiologia , Pele/efeitos da radiação , Análise de Variância , Proteínas Mutadas de Ataxia Telangiectasia/genética , Biópsia , Linhagem Celular , Reparo do DNA , Fibroblastos/efeitos da radiação , Humanos , Testes para Micronúcleos/métodos , Fosforilação , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Tolerância a Radiação/genética , Pele/patologia , Fatores de Tempo
20.
Brain ; 127(Pt 9): 1993-2009, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15289270

RESUMO

Neurofibromatosis 1 (NF1) is a common disease which is a source of various multisystemic manifestations related either to the accumulation of neurofibromas or to specific developmental abnormalities. The neurofibroma is the hallmark lesion of NF1 and develops from peripheral nerves. However, to date, the description of peripheral neuropathies of NF1 has not been investigated. To examine this question, we have evaluated 688 NF1 patients for the presentation, prognosis and associated morbidity of peripheral neuropathies in two hospital-based series. We collected 18 patients (four women and 14 men) with diffuse peripheral neuropathy (2.3%). Eight patients had a paucisymptomatic or an asymptomatic neuropathy detected only on electrophysiological study, two had minor sensory manifestations, five had moderate motor and sensory manifestations and three had severe motor and sensory manifestations. Superimposed radicular changes were observed in seven cases. Two patients had a subacute and 16 a chronic polyneuropathy. Fourteen patients had a demyelinating neuropathy with either severe axonal changes (three), moderate or minor axonal changes (four) or no axonal changes (seven). Four patients had axonal neuropathies. There was a strong association between the presence of a peripheral neuropathy and large root diffuse neurofibromas (P < 0.03) and subcutaneous neurofibromas (P < 0.0001). Severe morbidity and mortality of patients with NF1 and peripheral neuropathies was 50%, much higher than what is observed in the general population of patients with NF1, and 100% in patients with the most severe symptoms and electrophysiological changes (demyelination with severe axonal features). Four patients out of 18 (22%) developed a malignant peripheral nerve sheath tumour (MPNST), a much higher proportion than in the whole population of NF1. Two patients died. Peripheral neuropathy constitutes a potentially severe complication in patients with NF1 associated with a frequent morbidity related to spinal complications and MPNSTs. Association of proximal large neurofibromas, peripheral neuropathies and subcutaneous neurofibromas may constitute a phenotype of NF1 with a severe prognosis.


Assuntos
Neurofibromatose 1/patologia , Doenças do Sistema Nervoso Periférico/patologia , Adolescente , Adulto , Axônios/patologia , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Morbidade , Atividade Motora/fisiologia , Neoplasias de Bainha Neural/complicações , Neoplasias de Bainha Neural/patologia , Condução Nervosa/fisiologia , Neurofibromatose 1/complicações , Doenças do Sistema Nervoso Periférico/complicações , Prognóstico , Transtornos de Sensação/complicações , Transtornos de Sensação/patologia , Índice de Gravidade de Doença , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA