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BACKGROUND: To evaluate the efficacy of bevacizumab on reduction of the enucleation rate and control of intraocular pressure (IOP) in neovascular glaucoma (NVG)-complicating proton beam therapy for UM and to identify the determinants of the efficacy of bevacizumab. METHODS: Retrospective comparative study of patients with rubeosis following proton therapy for uveal melanoma. Patients were divided into two groups: a bevacizumab group and a control group which comprised two subgroups: panretinal photocoagulation (PRP)/cryotherapy and observation subgroups. Bevacizumab was administered by three intravitreal injections at 1-month intervals. A second series of injections was administered when necessary. Data concerning IOP and the secondary enucleation rate were collected and compared between the two groups. Univariate and multivariate analyses were performed to determine predictive factors of response to bevacizumab. RESULTS: A total of 169 patients who developed rubeosis following proton therapy between 2006 and 2016 were included: 44 patients in the bevacizumab group and 125 in the control group (38 in the PRP/cryotherapy subgroup and 87 in the observation subgroup). The two groups presented the same baseline characteristics apart from hypertension, retro-equatorial site, and proximity of the optic disk, which were more frequent in the control group, while initial retinal detachment and larger tumor volume were more frequent in the bevacizumab group. After a mean follow-up of 31 months, IOP was less than 21 mmHg in 54.54% of patients after IVB versus 72.7% before treatment (p = 0.06). Statistical analysis did not reveal any statistically significant reduction of the enucleation rate in the bevacizumab group compared to the observational group, whereas the PRP/cryotherapy group showed better eye retention rate (p = 0.15). No enucleation was performed when IOP was < 21 mmHg before IVB. Multivariate analysis identified initial IOP < 21 mmHg and UM situated away from the macula as predictive factors of good response to bevacizumab. CONCLUSION: Despite the improvement of IOP level, intravitreal bevacizumab (IVB) did not reduce the overall enucleation rate in NVG following proton beam therapy. Nevertheless, this treatment was effective in the early phases of NVG or as preventive treatment. PRP remains a valid treatment for NVG.
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Bevacizumab/administração & dosagem , Glaucoma Neovascular/tratamento farmacológico , Pressão Intraocular , Melanoma/radioterapia , Terapia com Prótons/efeitos adversos , Neoplasias Uveais/radioterapia , Acuidade Visual , Inibidores da Angiogênese/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Glaucoma Neovascular/diagnóstico , Glaucoma Neovascular/etiologia , Humanos , Injeções Intravítreas , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Uveais/diagnósticoRESUMO
BACKGROUND: Orbital rhabdomyosarcoma (ORMS) is associated with an excellent survival rate greater than 85%, and is considered to be a favourable site for this tumour. Treatment is based on combination chemotherapy together with best local therapy, sometimes surgery but more often radiation therapy. Local therapy is associated with frequent and potentially severe late sequelae. DESIGN: Retrospective hospital single-centre analysis. PARTICIPANTS: Eighty-two patients treated in Institut Curie, Paris. METHODS: To define long-term status of survivors after localized ORMS, patients treated between 1975 and 2010 were analysed. MAIN OUTCOME MEASURES: Clinical structural and functional orbital, and general sequelae. RESULTS: Median age at diagnosis was 6 years (range: 8 months-19 years), and median follow up was 8.5 years (range: 7 months-24 years). The 5-year globe conservation rate was 90.4%. Ophthalmic dysfunction was present in 79% of patients. Impaired visual acuity (VA), was present in 62% of patients; 38% of them had severe visual disability with VA < 6/60. Late effects on orbitofacial structure were present in 39.8% of patients. Ocular or palpebral sequelae were present in 79% of survivors, mainly cataract (42%), ocular surface lesions such as keratoconjunctivitis (40%) and eyelid abnormalities (29%). General late effects were rare. CONCLUSIONS: These data suggest that ocular and orbital late effects are frequent after treatment of ORMS, indicating the need for systematic long-term ophthalmologic follow up of these patients. Radiation therapy is an important part of the total burden of therapy.
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Neoplasias Orbitárias/patologia , Rabdomiossarcoma/patologia , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasias Orbitárias/mortalidade , Neoplasias Orbitárias/terapia , Complicações Pós-Operatórias , Radioterapia , Estudos Retrospectivos , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/terapia , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Orbital rhabdomyosarcoma (ORMS) treatment is based on combination chemotherapy associated with best local therapy, sometimes surgery but more often radiation therapy. A retrospective single-center analysis was conducted to more clearly define the long-term outcome of patients with ORMS, to identify patients in whom aggressive first-line local therapy can be avoided. POPULATION: A total of 95 patients with localized parameningeal (PM) or nonparameningeal (NPM) ORMS, treated at the Institut Curie between 1975 and 2010, were analyzed. RESULTS: Median age at diagnosis was 6 years (range, 8 mo to 19.5 y), and median follow-up was 8.5 years (range, 7 mo to 24 y). A total of 25 patients presented PM extension. Radiation therapy was part of primary therapy for 78 patients. Five-year event-free survival and overall survival rates were 65.4%±5.2% and 85.6%±3.9%, respectively. On multivariate analysis, initial tumor size was identified as a significant prognostic factor. Event-free survival was similar for PM and NPM tumors (60.3%±10.4% vs. 62.7%±5.9%, P=0.57), whereas there was a trend for overall survival to be better for NPM tumors (90%±3.9% vs. 72.7%±9.6%, P=0.07). CONCLUSIONS: Localized ORMS has a favorable outcome despite the current trend toward less aggressive and more limited indications of local therapy. Patients with a favorable pattern of strictly ORMS can be treated without first-line radiation therapy.
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Quimiorradioterapia/métodos , Neoplasias Orbitárias/terapia , Rabdomiossarcoma/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Dactinomicina/uso terapêutico , Intervalo Livre de Doença , Epirubicina/uso terapêutico , Seguimentos , Humanos , Ifosfamida/uso terapêutico , Lactente , Estadiamento de Neoplasias , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/patologia , Prognóstico , Cintilografia , Estudos Retrospectivos , Rabdomiossarcoma/diagnóstico por imagem , Rabdomiossarcoma/patologia , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto JovemRESUMO
Introduction: Intraocular localization of conjunctival squamous cell carcinoma (SCC) is due to scleral or corneal invasion. Herein, we describe the clinical and histopathological findings in four cases of SCC complicated by intraocular invasion, and we review cases reported in the literature and their management. We retrospectively collected and analyzed clinical characteristics, histopathology, management, and follow-up data from 4 patients with conjunctival SCC complicated by intraocular invasion. We reviewed the literature and summarized cases of intraocular invasion by conjunctival SCC reported over the last 30 years. Case Presentations: Two patients presented with intraocular invasion by conjunctival SCC at diagnosis. The two others developed intraocular invasion as recurrence of conjunctival SCC, previously treated with excisional biopsy and adjuvant radiotherapy. All 4 cases had a previous history of conjunctival surgery, but no history of intraocular surgery. Three patients were managed with modified enucleation, including one that required adjuvant orbital radiotherapy. One patient required orbital exenteration. Histopathology analysis showed a well-differentiated conjunctival SCC in all cases. None developed distant localization after at least 2.5-year follow-up. Discussion/Conclusion: Intraocular invasion is a rare complication of conjunctival SCC. Appropriate treatment in a tertiary center and long-term follow-up are highly recommended.
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BACKGROUND: The aim of this study was to screen for musculoskeletal disorders (MSD) complaints, to analyse the activity and to identify their risk factors. MATERIALS AND METHODS: This cross-sectional epidemiological study involved 903 men aged > 20 years and with a seniority > 2 years. It included a questionnaire and an ergonomic analysis of the activity. The questionnaire included: socio-demographic and occupational characteristics, health status and life habits, stress and items from the Nordic questionnaire. The observation of work situations required video recordings and the use of three methods: Occupational Safety and Health Administration (OSHA), Rapid Upper Limb Assessment (RULA) and the Gesture Tracking and Assessment Tool (Outil de Repérage et d'Évaluation des Gestes: OREGE). RESULTS: The prevalence of MSDs was 61.9%. It was significantly higher among deckhands than among other professionals (65.6% vs 27.4%; p < 0.001) and in seasonal workers than in permanent workers (67.8% vs 43.1%; p < 0.001). A positive correlation was noted between MSDs and daily work duration. Stress was an aggravating factor, whereas leisure activities were protective. The prevalence of MSDs was 40.5% (lower back), 40.4% (wrist/hand joints), 34.6% (neck) and 31.7% (shoulders). The ergonomic analysis of the workstation was performed on a deckhand who unloaded the fish crates out of the hold of a trawler. OSHA score = 12 (normal < 5); significant risk of upper limb MSD. RULA total score = 7 (acceptable between 1 and 2); immediate modification. OREGE scores evaluating effort, repetitiveness and joint positions indicate that the actions were not recommended or to be avoided. CONCLUSIONS: The analysis made it possible to evaluate the difficulty of the job and to note a high risk of MSDs requiring ergonomic and organizational improvements.
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Ergonomia , Doenças Musculoesqueléticas , Doenças Profissionais , Humanos , Masculino , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/etiologia , Adulto , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Estudos Transversais , Pessoa de Meia-Idade , Fatores de Risco , Prevalência , Pesqueiros , Inquéritos e Questionários , Medicina Naval , Adulto JovemRESUMO
BACKGROUND: Coastal fishermen are particularly affected by occupational stress and burnout because they are exposed to high psychosocial factors at work and organizational constraints related to difficult working conditions. MATERIALS AND METHODS: This survey aimed to assess the prevalence of burnout syndrome (BOS) of fishermen and its relationship with sociodemographic and occupational parameters. This cross-sectional study involved a representative sample of 761 fishermen. We used an individual questionnaire including socio-demographic and occupational parameters, the Karasek's Job Content Questionnaire, and Maslach BO Inventory. BOS includes three dimensions: emotional exhaustion, depersonalisation, and loss of self-efficacy. The positive diagnosis of BOS is retained if the scores of the three dimensions are abnormal (high for the first two and low for the third). RESULTS: Five hundred and twenty-six people agreed to answer the questionnaire. Of these, 16.1% had a high emotional exhaustion, 13.9% high depersonalisation, and 11.2% low personal accomplishment. Furthermore, 37.1% had at least one abnormal dimension of BOS: 16.9% had one abnormal dimension, 12.2% two, and 8% three (BOS). The prevalence of abnormal dimensions of BOS was significantly higher in pilots-copilots (67.9%), and in mechanics (63.5%) than in sailors (27.8%). It was higher in fishermen living alone (44.4%), having seasonal job (57.9%), suffering of job strain (42.1%) or isostrain (57.9%), and sleep disorders (55.4%). The multivariate logistic regression showed that job strain, isostrain, fatigue, sleep disorders, seasonal job and daily working > 14 h constituted a major risk factor of abnormal dimension of BOS. CONCLUSIONS: It is imperative to identify priority actions to improve the working conditions of fishermen, and to develop a genuine prevention policy.
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Esgotamento Profissional , Estresse Ocupacional , Humanos , Estudos Transversais , Estresse Ocupacional/epidemiologia , Estresse Ocupacional/psicologia , Esgotamento Profissional/epidemiologia , Inquéritos e Questionários , Ansiedade , Satisfação no EmpregoRESUMO
BACKGROUND: The aim of this survey was to assess the health status, sleep habits and dyssomnia of coastal fishermen. MATERIALS AND METHODS: This cross-sectional survey involved a representative sample of 948 coastal fishermen. All participants were men and had a regular activity for at least 2 years. We used an individual questionnaire inspired by those of Morphée network, the National Institute for Research and Security of France, and of the Karasek's Job Content Questionnaire. RESULTS: The prevalence of sociodemographic and individual parameters was similar in rotating shiftwork (RW) and in nocturnal work (NW). The average age of the total population was 38.8 ± 8.1 years. The prevalence of sleep habits and alertness disorders was similar in RW and in NW. The average daily sleep time of the total population was 5.5 ± 0.9 hours during the week, and 8.7 ± 0.8 hours during the holidays, Fridays and recovery days. Upon waking, 49.7% of the subjects felt tired and sleepy, 43.2% fit and 7.1% had a headache. 47.2% reported being chronic insomniac. The index of severity of insomnia was moderate to severe in 29.6%. The prevalence of excessive daytime sleepiness (Epworth > 10) was 16.2%. Fatigue, iso-strain and socio-economic concerns were associated with a higher risk of chronic insomnia. CONCLUSIONS: Coastal fishermen were at a high risk of chronic dyssomnia and alertness disorders. Education initiatives should be conducted to raise fishermen's awareness on their health and safety consequences.
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Distúrbios do Sono por Sonolência Excessiva , Distúrbios do Início e da Manutenção do Sono , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Estudos Transversais , Sono , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Sono por Sonolência Excessiva/epidemiologia , Inquéritos e Questionários , Fadiga/epidemiologia , Nível de Saúde , PrevalênciaRESUMO
The world is currently facing an unprecedented pandemic crisis. The highly contagious coronavirus, or COVID-19, first occurred in Wuhan (China) in December 2019. The outbreak of the virus quickly spread all over the world, reaching Europe in January 2020. The first case in Germany was reported to be diagnosed on January 27. This study focuses on assessing the mental health consequences of the German public during COVID-19 outbreak. Psychological discomfort, generalized anxiety disorder, sleep disturbances, depressive symptoms and threat perception are especially investigated with respect to demographics, security importance and negative affectivity. The psychological vulnerabilities that go along with the pandemic are evaluated in detail. The cross-sectional online survey conducted in Germany reveals a prevalence of depressive symptoms, psychological discomfort, threat perception, generalized anxiety disorder and sleep disturbances associated with the pandemic crisis. The results also indicate a relationship between mental health issues and negative affectivity as well as the perception of threat. This paper gives an outlook on long-term consequences and what could be the strategies to mitigate the negative mental health outcomes of the crisis.
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OBJECTIVE: Localized orbital rhabdomyosarcoma (oRMS) has an overall favourable prognosis with more than 90% of survival. Little is known about the best strategy in recurrent/refractory (R/R) cases. The purpose is to examine the characteristics of patients with R/R-oRMS, focusing on local therapy. METHODS: This is bicentric retrospective study. Analysis is of young patients (<30 years) with R/R-oRMS who were treated from 1989 to 2018 at the Institut Curie and Gustave Roussy Cancer Campus, France. RESULTS: Twenty-seven out of 162 patients (17%) with oRMS presented with R/R disease. 6 of these patients had alveolar RMS (22%), 3 of whom had initial parameningeal extension (11%). During first-line treatment, 18 patients (67%) had orbital radiotherapy. Median age at R/R was 10 years (ranges: 4-28) after a delay of 19 months from diagnosis (ranges: 3-40). Tumoral events were local relapses (22 cases), local progression (3 cases) or regional relapses (2 cases). Second-line treatments included chemotherapy (27 cases), radiotherapy (16 cases), surgery (exenteration; 8 cases) and metastasis/ nodal removal (3 cases). After a median follow-up of 99 months (range: 10-306), 4 patients died and 23 are in complete remission (CR) without treatment. One patient had subsequent relapse treated with exenteration and brachytherapy until a new tumour remission. Five-year event-free and overall survivals after first tumour event are, respectively, 84.4% (95% confidence interval: 71.5%-98.8%) and 85.8% (95% confidence interval: 72.1%-100.0%) CONCLUSION: R/R-oRMS is a rare situation. Second-line therapy is efficient in this location, sometime at the cost of lifesaving mutilating surgery. Second-line local therapy needs therefore to consider local radiotherapy if possible or complete wide surgery.
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Antineoplásicos/uso terapêutico , Recidiva Local de Neoplasia/terapia , Neoplasias Orbitárias/terapia , Radioterapia/métodos , Rabdomiossarcoma/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Do leaders who build a sense of shared social identity in their teams thereby protect them from the adverse effects of workplace stress? This is a question that the present paper explores by testing the hypothesis that identity leadership contributes to stronger team identification among employees and, through this, is associated with reduced burnout. We tested this model with unique datasets from the Global Identity Leadership Development (GILD) project with participants from all inhabited continents. We compared two datasets from 2016/2017 (n = 5290; 20 countries) and 2020/2021 (n = 7294; 28 countries) and found very similar levels of identity leadership, team identification and burnout across the five years. An inspection of the 2020/2021 data at the onset of and later in the COVID-19 pandemic showed stable identity leadership levels and slightly higher levels of both burnout and team identification. Supporting our hypotheses, we found almost identical indirect effects (2016/2017, b = -0.132; 2020/2021, b = -0.133) across the five-year span in both datasets. Using a subset of n = 111 German participants surveyed over two waves, we found the indirect effect confirmed over time with identity leadership (at T1) predicting team identification and, in turn, burnout, three months later. Finally, we explored whether there could be a "too-much-of-a-good-thing" effect for identity leadership. Speaking against this, we found a u-shaped quadratic effect whereby ratings of identity leadership at the upper end of the distribution were related to even stronger team identification and a stronger indirect effect on reduced burnout.
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COVID-19 , Liderança , Esgotamento Psicológico , Humanos , Pandemias , SARS-CoV-2RESUMO
Radiotherapy (RT) is the standard treatment for high-grade gliomas. However, toxicity may develop during RT, such as brain edema or worsening of neurological symptoms. Surprisingly, no dedicated study had focused on steroid requirements during RT in adult patients with malignant gliomas. We evaluated prospectively all patients with malignant gliomas treated by RT in a single center from July 2006 to May 2009. Age, sex, initial Karnofsky performance status (KPS), tumor localization and histology, type of surgical resection, clinical target volume, total dose and duration of RT, concomitant treatment with temozolomide, and steroid dosage during RT and at 1 and 3 months after RT were recorded in all patients. Most of the 80 patients (70%) were already taking steroids before RT. Half of them (55%) required initiation or further steroids increase during RT. The median time to steroid increase was 8 days. Only 13% of patients remained free of steroids during RT, and the mean maximal dosage of prednisone was 55 ± 48 mg. At 3 months after RT, 29% of patients were free of steroids, and the mean prednisone dosage was 32 ± 50 mg. Unresected tumors and initial KPS ≤80% were the only variables associated with higher steroid requirements on multivariate analysis. In our series, almost all patients required steroids during RT. Poor initial KPS and biopsy were associated with higher steroid requirements.
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Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Radioterapia/efeitos adversos , Esteroides/administração & dosagem , Esteroides/metabolismo , Fatores Etários , Idoso , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Terapia Combinada , Fracionamento da Dose de Radiação , Feminino , Glioma/radioterapia , Glioma/cirurgia , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Estudos Retrospectivos , Fatores de TempoRESUMO
PURPOSE: Human, material, and financial resources being limited, the organization of the care system must allow an efficient allocation of resources. The management of cancers leads to specific and repetitive care for which the reimbursement of transport costs represents a high cost. We carried out an analysis of the additional transport costs, linked to the care of patients in Île-de-France, in a center other than the radiotherapy center closest to their home. MATERIALS AND METHODS: Using data from the Île-de-France Regional Health Agency, we have created a model evaluating the additional cost linked to transport generated by the care of a radiotherapy patient far from his home. In order to take into account the uncertainties linked to the hypotheses made in the development of the model, we carried out deterministic and probabilistic sensitivity analyzes. RESULTS: In the base case, the additional annual cost related to transport was 841,176 euros in Île-de-France. The probabilistic sensitivity analysis reports a total annual additional cost of 2,817,481 euros. CONCLUSION: Our results are similar to a report from the General Inspectorate of Social Affairs published in July 2011, which then pointed to an additional cost of between 4 and 6 million euros annually. The long-term care of cancer patients from their homes contributes to a deterioration in the quality of life linked to travel times, a delay in the care of potential treatment complications, and the spread of infectious diseases, such as COVID-19, and bacteria resistant to antibiotics.
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Ambulâncias/economia , Institutos de Câncer/provisão & distribuição , Acessibilidade aos Serviços de Saúde/economia , Neoplasias/radioterapia , Transporte de Pacientes/economia , Ambulâncias/estatística & dados numéricos , Custos e Análise de Custo , França , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Modelos Estatísticos , Neoplasias/economia , Paris , Qualidade de Vida , Alocação de Recursos , Fatores de Tempo , Transporte de Pacientes/estatística & dados numéricos , IncertezaRESUMO
Introduction: Lacrymal cystic adenoid carcinoma is a rare disease for which optimal treatment is still debated. In fact, despite aggressive treatment such as eye sparing surgery or orbital exenteration, following by adjuvant radiotherapy, local recurrence and distant metastatic disease are common. This study aims to describe outcomes of eye surgery associated with high dose exclusive adjuvant proton beam irradiation. Materials and Methods: This is a monocentric institutional retrospective study. We retrospectively reviewed records of patients treated in our institution since 2008 with high dose adjuvant proton irradiation for a lacrymal cystic adenoid carcinoma up to a maximum of 75.6Gy(RBE). Other histologies or patients treated with a mix of photon-proton were excluded. A total of 15 patients were finally included. Results: Fifteen patients (80% women, 100% Performance status 0-1) with locally advanced disease (33% T3-T4, 47% R1-R2) were included. After a median follow-up of 67.4 months [13.4-122] the 3 years Overall Survival, local Progression free survival, and progression free survival rates were 78, 70, and 58%, respectively. Six patients exhibited a local recurrence. All patients with conservative surgery maintained their base-line visual acuity and visual field at last follow up. Four patients developed brain radionecrosis. Conclusion: This is the largest series of patients with ACC treated with high dose adjuvant proton therapy. Proton therapy is a safe and efficient treatment and should be considered as an adjuvant irradiation modality to privilege, for patients with lacrimal ACC after conservative or radical eyeball surgery. Dose delivered to temporal lobe should be limited to avoid brain radionecrosis.
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Importance: Retinoblastoma (RB) is the most common pediatric intraocular neoplasm. RB is a complex model in which atypical pathogenic variants, modifier genes, imprinting, and mosaicism are known to be associated with the phenotype. In-depth understanding of RB therefore requires large genotype-phenotype studies. Objective: To assess the association between genotype and phenotype in patients with RB. Design, Setting, and Participants: This single-center, retrospective cohort study, conducted from January 1, 2000, to September 30, 2017, enrolled 1404 consecutive ascertained patients with RB who consulted an oncogeneticist. All patients had their genotype and phenotype recorded. Statistical analysis was performed from July 1, 2018, to December 31, 2018. Main Outcomes and Measures: RB1 germline and somatic pathogenic variant types, family history, and disease presentation characteristics (ie, age at diagnosis, sex, laterality, and International Intraocular Retinoblastoma Classification group). Results: Among 1404 patients with RB (734 [52.3%] female; mean [SD] age, 20.2 [21.2] months), 866 cases (61.7%) were unilateral and 538 cases (38.3%) were bilateral. Loss of function variants were found throughout the coding sequence, with 259 of 272 (95.2%) somatic pathogenic variants and 537 of 606 (88.6%) germline pathogenic variants (difference, 6.6%; 95% CI, 4.0%-9.2%; P < .001) after excluding tumor-specific pathogenic variants (ie, promoter methylation and loss of heterozygosity); a novel low-penetrance region was identified in exon 24. Compared with germline pathogenic variants estimated to retain RB protein expression, germline pathogenic variants estimated to abrogate RB protein expression were associated with an earlier mean (SD) age at diagnosis (12.3 [11.3] months among 457 patients vs 16.3 [13.2] months among 55 patients; difference, 4 months; 95% CI, 1.9-6.1 months; P = .01), more frequent bilateral involvement (84.2% among 452 patients vs 65.2% among 45 patients; difference, 18.9%; 95% CI, 14.5%-23.3%; P < .001), and more advanced International Intraocular Retinoblastoma Classification group (85.3% among 339 patients vs 73.9% among 34 patients; difference: 11.4%; 95% CI, 6.5%-16.3%; P = .047). Among the 765 nongermline carriers of an RB1 pathogenic variant, most were female (419 females [54.8%] vs 346 males [45.2%]; P = .008), and males were more likely to have bilateral RB (23 males [71.4%] vs 12 females [34.3%]; P = .01). Conclusions and Relevance: These results suggest that RB risk is associated with the germline pathogenic variant and with maintenance of RB protein and that there is a sex-linked mechanism for nongermline carriers.
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Estudos de Associação Genética , Neoplasias da Retina/genética , Proteínas de Ligação a Retinoblastoma/genética , Retinoblastoma/genética , Ubiquitina-Proteína Ligases/genética , Adolescente , Adulto , Criança , Pré-Escolar , DNA de Neoplasias/genética , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Lactente , Recém-Nascido , Masculino , Penetrância , Neoplasias da Retina/patologia , Retinoblastoma/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
We studied 50 unrelated pedigrees with a family history of retinoblastoma (Rb) (165 carriers of a RB1 mutation) to delineate the spectrum of RB1 germline mutations in familial Rb and to identify genotype-phenotype correlations as well as putative modifiers. Patients were followed at Institut Curie and they were examined by an ophthalmologist, a pediatrician, and a geneticist. All cases of familial Rb were determined via genetic counseling. Clinical features included disease status, laterality, age at diagnosis, mutation type, follow-up, and disease-eye ratio (DER). To eliminate mosaic cases, first-generation carriers displaying low-penetrance (LP) Rb were excluded from the analysis. Complete penetrance was the rule for nonsense and frameshift mutations (25 families) and high penetrance was observed for large rearrangements (eight families). Promoter (two families) and missense (two families) mutations displayed heterogeneous phenotypes and LP. Variable penetrance was observed for splice abnormalities (13 families) and was explained by in/out of frame mutations or respect of functional domains. Surprisingly, two families with the LP g.45867G>T/IVS6+1G>T mutation presented data that conflicted with the data reported in previous publications, as unaffected carriers had paternally inherited mutant alleles. Moreover, RNA analyses suggested that the lack of penetrance in unaffected carriers could be explained by an increase in expression levels of the wild-type allele. This observation prompted us to define a new class "3" of LP alleles. We believe this is the first large-scale study of familial Rb with a high level of homogeneity in the clinical and genetic analysis of patients and their relatives, thereby allowing for reliable intrafamilial genotype-phenotype correlations. Our analysis suggests in some cases the influence of modifier factors probably involved in mRNA level regulation and/or pRB pathway regulation.
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Fenótipo , Neoplasias da Retina/genética , Retinoblastoma/genética , Pré-Escolar , Aberrações Cromossômicas , Cromossomos Humanos Par 13 , Códon sem Sentido/análise , Feminino , Mutação da Fase de Leitura , Genes do Retinoblastoma , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Linhagem , Sítios de Splice de RNA/genéticaRESUMO
PURPOSE: This study reports the results of proton beam radiotherapy based on a retrospective series of patients treated for uveal melanoma at the Orsay Center. METHODS AND MATERIALS: Between September 1991 and September 2001, 1,406 patients with uveal melanoma were treated by proton beam radiotherapy. A total dose of 60 cobalt Gray equivalent (CGE) was delivered in 4 fractions on 4 days. Survival rates were determined using Kaplan-Meier estimates. Prognostic factors were determined by multivariate analysis using the Cox model. RESULTS: The median follow-up was 73 months (range, 24-142 months). The 5-year overall survival and metastasis-free survival rates were 79% and 80.6%, respectively. The 5-year local control rate was 96%. The 5-year enucleation for complications rate was 7.7%. Independent prognostic factors for overall survival were age (p < 0.0001), gender (p < 0.0003), tumor site (p < 0.0001), tumor thickness (p = 0.02), tumor diameter (p < 0.0001), and retinal area receiving at least 30 CGE (p = 0.003). Independent prognostic factors for metastasis-free survival were age (p = 0.0042), retinal detachment (p = 0.01), tumor site (p < 0.0001), tumor volume (p < 0.0001), local recurrence (p < 0.0001), and retinal area receiving at least 30 CGE (p = 0.002). Independent prognostic factors for local control were tumor diameter (p = 0.003) and macular area receiving at least 30 CGE (p = 0.01). Independent prognostic factors for enucleation for complications were tumor thickness (p < 0.0001) and lens volume receiving at least 30 CGE (p = 0.0002). CONCLUSION: This retrospective study confirms that proton beam radiotherapy ensures an excellent local control rate. Further clinical studies are required to decrease the incidence of postirradiation ocular complications.
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Melanoma/radioterapia , Terapia com Prótons , Neoplasias Uveais/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Enucleação Ocular/estatística & dados numéricos , Feminino , Humanos , Melanoma/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Uveais/mortalidadeRESUMO
Epidemiologic studies have reported an association between lymphoid neoplasia and melanoma. However, the clinical characteristics, medical history and outcome of patients presenting both diseases have not been clearly described. Patients who developed both lymphoma and melanoma at the Institut Curie between 1970 and 2005 were included in this retrospective study. Patient characteristics were analysed and a review of all previously published cases was then performed. The eight patients of our series and those derived from a review of the literature resulted in a population of 70 patients. The male/female sex ratio was greater than 1. Patients were older than 50 years. The mean interval to the second malignancy was 5 years and 13 years for lymphoma and melanoma, respectively. Most patients had an indolent B-cell lymphoma and localized melanoma. Frequent skin involvement was reported for T-cell lymphoma. Chemotherapy or external radiation therapy frequently preceded the second malignancy. Patients with lymphoma and melanoma should be closely monitored to detect the appearance of a second malignancy. Further studies are therefore warranted to elucidate this peculiar association.
Assuntos
Linfoma/complicações , Linfoma/diagnóstico , Melanoma/complicações , Melanoma/diagnóstico , Adulto , Idoso , Neoplasias Oculares/complicações , Neoplasias Oculares/diagnóstico , Feminino , Humanos , Linfoma/epidemiologia , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico , Estudos Retrospectivos , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/diagnóstico , Fatores de TempoRESUMO
To define the initial characteristics and prognostic factors of patients with conjunctival low-grade malignant lymphoma, all patients treated for low-grade lymphoma with initial conjunctival involvement were reviewed. Forty-nine cases were selected, including 45 cases with exclusive ophthalmologic conjunctival involvement. Pathologic review showed 55% of mucosa-associated lymphoid tissue type lymphoma, and 23% of lymphoplasmocytic lymphoma. Initial characteristics were median age of 62 years, nodal involvement in 17% of cases, and stage IV in 22% of patients with 10% of bone marrow involvement. With a median follow-up of 75 months, the 5-year disease-free survival (DFS) and overall survival were 65% and 83%, respectively. On multivariate analysis, nodal involvement was the only factor with a pejorative impact on DFS. Our patient cohort represents one of the largest published series defining the characteristics and prognostic factors of primary conjunctival low-grade malignant lymphoma.
Assuntos
Neoplasias da Túnica Conjuntiva/diagnóstico , Neoplasias da Túnica Conjuntiva/patologia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/patologia , Fatores Etários , Neoplasias da Túnica Conjuntiva/terapia , Intervalo Livre de Doença , Feminino , Humanos , Linfoma não Hodgkin/terapia , Masculino , Análise Multivariada , Prognóstico , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
Glioblastoma patients often require chronic administration of steroids due to peri-tumoral edema. Preliminary studies showed that treatment with Angiotensin-II Receptor Blockers (ARBs) for high blood pressure might be associated with reduced peri-tumoral edema. In this study, we aim to radiologically assess the effect of ARBs on peri-tumoral edema. We conducted a cross-sectional survey on patients with newly diagnosed GBM. Patients treated with ARBs for high blood pressure were paired to non ARB-treated patients based on similar age, tumor location and tumor size. Patients taking steroids at the time of pre-operative Magnetic Resonance Imaging were excluded from the study. In each pair of patients, we compared the volumes of peri-tumoral hyper T2-Fluid Attenuated Inversion Recovery (FLAIR) signal and the Apparent Diffusion Coefficient (ADC) in the same area. Eleven (11) ARB-treated patients were selected and paired to 11 non ARB-treated controls. Volumes of peri-tumoral hyper T2-FLAIR signal were significantly lower in the ARB-treated group than in the non ARB-treated group (p = 0.02). Additionally, peri-tumoral ADCs were also significantly lower in the treated group (p = 0.02), suggesting that the peri-tumoral area in this group had less edematous features. These results suggest that ARBs may reduce the volume of peri-tumoral hyper T2-FLAIR signal by decreasing edema.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Neoplasias Encefálicas/complicações , Glioblastoma/complicações , Idoso , Edema Encefálico/diagnóstico por imagem , Mapeamento Encefálico , Neoplasias Encefálicas/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Glioblastoma/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não ParamétricasRESUMO
Conspiracy theory (CT) beliefs can be harmful. How is it possible to reduce them effectively? Three reduction strategies were tested in an online experiment using general and well-known CT beliefs on a comprehensive randomly assigned Hungarian sample (N = 813): exposing rational counter CT arguments, ridiculing those who hold CT beliefs, and empathizing with the targets of CT beliefs. Several relevant individual differences were measured. Rational and ridiculing arguments were effective in reducing CT, whereas empathizing with the targets of CTs had no effect. Individual differences played no role in CT reduction, but the perceived intelligence and competence of the individual who conveyed the CT belief-reduction information contributed to the success of the CT belief reduction. Rational arguments targeting the link between the object of belief and its characteristics appear to be an effective tool in fighting conspiracy theory beliefs.