RESUMO
OBJECTIVE: To study the relevance of liver function test (LFT) results for early detection of liver metastasis of uveal melanoma. DESIGN: Evaluation of diagnostic test. PARTICIPANTS: Eighty-eight patients were included in whom metastasis developed while undergoing semiannual follow-up with LFTs, including aspartate-aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (γGT), lactate dehydrogenase (LDH), and phosphatase alkaline (PA). As controls, 174 patients with uveal melanoma without metastasis were included. METHODS: The diagnostic attributes of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each test were estimated from cross-tabulation tables of test results according to the diagnosis of metastasis. The proportions of false-positive results between groups of patients with and without metastasis were compared in log-binomial regression models. MAIN OUTCOME MEASURES: Sensitivity, specificity, PPV, NPV, and cost evaluation. RESULTS: Metastases were detected after LFT abnormality (at least 1 abnormal test result) in 40 (45%) patients. The overall sensitivity of LFTs ranged from 12.5% to 58.0%, and the PPV ranged from 9.4% to 38.6%. The overall specificity and NPV were 90% or greater. The proportions of false-positive results between groups of patients with and without metastasis did not differ significantly (all P≥0.38). Using a cost evaluation, semi-annual screening by LFTs was calculated to cost $35.5/year per patient, including liver imaging induced by true and false-positive results. CONCLUSIONS: Isolated or combined LFTs for AST, ALT, γGT, LDH, and PA are not helpful for detection of early metastasis. However, the high NPVs suggest that LFT screening can allow clinicians to reassure the patient when the LFT results are negative.
Assuntos
Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Melanoma/diagnóstico , Neoplasias Uveais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Detecção Precoce de Câncer , Reações Falso-Positivas , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Testes de Função Hepática/economia , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/secundário , Masculino , Melanoma/enzimologia , Melanoma/secundário , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Adulto Jovem , gama-Glutamiltransferase/sangueRESUMO
We present the case of a 56-year-old man who developed a neoplasm of epithelioid histology in his anophthalmic left orbit 21 years after he underwent enucleation for a spindle cell iris melanoma. The recurrent tumour was managed by orbital exenteration. Neither further recurrence nor metastasis was diagnosed over a 5-year follow-up period. This case, along with five other similar cases in the literature,1-3 emphasises the importance of long-term follow-up after treatment of iris melanoma.
Assuntos
Enucleação Ocular/efeitos adversos , Neoplasias da Íris/patologia , Melanoma/patologia , Neoplasias Orbitárias/patologia , Humanos , Neoplasias da Íris/cirurgia , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Exenteração Orbitária/métodos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: This study aimed to assess the ocular and metastatic outcomes of patients with choroidal indeterminate melanocytic lesions treated by primary transpupillary thermotherapy (TTT). DESIGN: Retrospective case series. PARTICIPANTS: Eight patients presenting choroidal indeterminate melanocytic lesions treated by primary TTT. METHODS: A retrospective chart review was conducted for patients with a newly diagnosed choroidal indeterminate melanocytic lesion treated by at least 3 TTT sessions from 2002 to 2011. Best-corrected visual acuity and lesion dimensions were measured at baseline and during follow-up. Complications were recorded including lesion growth, metastasis, melanoma-related mortality, and treatment-related complications. RESULTS: Mean initial thickness was 2.0 ± 0.8 mm. Patients had an average of 3.0 ± 0.9 risk factors for lesion growing. Three patients (38%) had lesion growth. Two patients (25%) had severe visual loss (>1.0 logMAR) directly related to TTT treatment. There were no fatalities due to metastasis. CONCLUSIONS: Despite careful patient selection and systematic treatment with at least 3 TTT sessions, the use of primary TTT to treat patients with choroidal indeterminate melanocytic lesions with ≥ 1 risk factor for lesion growth yielded poor local lesion control and the possibility for severe ocular complications.
Assuntos
Neoplasias da Coroide/terapia , Hipertermia Induzida/métodos , Nevo Pigmentado/terapia , Adulto , Idoso , Neoplasias da Coroide/mortalidade , Neoplasias da Coroide/patologia , Feminino , Seguimentos , Humanos , Hipertermia Induzida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nevo Pigmentado/mortalidade , Nevo Pigmentado/patologia , Pupila , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Acuidade Visual/fisiologiaRESUMO
PURPOSE: Overexpression of hypoxia inducible factor-1 α (HIF-1α) has been found in several cancers and is thought to correlate with aggressive disease. The purpose of our study was to investigate the influence of HIF-1α on clinical outcome in uveal melanoma (UM) along with proliferative (MIB-1) and vascular (CD31, VEGF-A) markers. METHODS: A retrospective analysis was carried out on UM tumors from 88 patients. HIF-1α, MIB-1, CD31, and VEGF-A expression, as well as necrosis, were assessed by immunohistochemistry and hematoxylin/eosin on paraffin-embedded UM tumor sections by using a tissue microarray. The bivariate analysis involving HIF-1α expression and clinicopathologic covariates was performed by using the χ(2) test. The association of clinicopathologic covariates and HIF-1α expression with patient survival was evaluated by using the Kaplan-Meier approach and Cox proportional-hazards regression analysis. RESULTS: Among our study population, 56 patients (63.6%) had high levels of HIF-1α expression. High expression of HIF-1α was associated with high expression of MIB-1 (P = 0.04), CD31 (P = 0.03), and VEGF-A (P < 0.0001), as well as necrosis (P = 0.04). However, high HIF-1α expression was not correlated with cell type, largest macroscopic tumor dimension or thickness, anterior margin, pigmentation, or mitotic figures. Patients with high HIF-1α expression did not show a reduced survival when compared to patients with low HIF-1α expression (P = 0.92). Finally, HIF-1α expression was not increased after irradiation. CONCLUSIONS: An increase in HIF-1α expression was significantly associated with proliferative (MIB-1) and vascular (CD31 and VEGF-A) markers, as well as necrosis, in UM. However, there was no correlation between high HIF-1α expression and patient survival.
Assuntos
Proliferação de Células , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Melanoma/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Neoplasias Uveais/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise Serial de Tecidos , Neoplasias Uveais/patologia , Adulto JovemAssuntos
Sistemas de Registro de Ordens Médicas/organização & administração , Erros de Medicação/prevenção & controle , Sistemas de Medicação no Hospital/organização & administração , Avaliação de Processos e Resultados em Cuidados de Saúde/organização & administração , Gestão da Segurança/organização & administração , Gestão da Qualidade Total/organização & administração , Interpretação Estatística de Dados , Esquema de Medicação , Tratamento Farmacológico/métodos , Tratamento Farmacológico/enfermagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Maine , Erros de Medicação/métodos , Erros de Medicação/enfermagem , Enfermeiros Administradores/organização & administração , Inovação Organizacional , Medição de Risco , Análise de Sistemas , Fatores de TempoRESUMO
PURPOSE: Poly(ADP-ribosyl)ation is a reversible post-translational modification that requires the contribution of the enzymes poly(ADP-ribose) polymerase-1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG). Our study explores expression and activity of PARP-1 and PARG in uveal melanoma cell lines with varying tumorigenic properties. METHODS: Gene profiling on microarrays was conducted using RNA prepared from the uveal melanoma cell lines T97, T98, T108, and T115. The activity of PARP-1 and PARG was monitored by enzymatic assays, whereas their expression was measured by Western blot and PCR. The PARG promoter was analyzed using promoter deletions and site-specific mutagenesis in transfection analyses. The transcription factors binding the PARG promoter were studied by electrophoretic mobility shift assay (EMSA) analyses. Suppression of PARP-1 and PARG expression was performed in T97 and T115 cells by RNAi, and their tumorigenic properties monitored by injections into athymic mice. RESULTS: Expression of PARP-1 was found to vary considerably between uveal melanoma cell lines with distinctive tumorigenic properties in vivo. Sp1 and the ETS protein ERM were shown to bind to the PARG gene promoter to ensure basal transcription in uveal melanoma. Importantly, suppression of PARG gene expression in T97 and T115 cells increased their capacity to form tumors in athymic mice, whereas suppression of PARP-1 significantly reduced or almost entirely abolished tumor formation. CONCLUSIONS: Our results suggest that while overexpression of PARP-1 may confer a proliferative advantage to aggressive uveal melanoma tumors, PARG may, on the other hand, support a tumor suppressor function in vivo.
Assuntos
Proteínas de Ligação a DNA/fisiologia , Proteínas Ativadoras de GTPase/metabolismo , Regulação Neoplásica da Expressão Gênica , Melanoma/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Fatores de Transcrição/fisiologia , Neoplasias Uveais/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Melanoma/genética , Camundongos , Camundongos Nus , Análise em Microsséries , Análise de Sequência com Séries de Oligonucleotídeos , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/genética , Reação em Cadeia da Polimerase , Neoplasias Uveais/genéticaRESUMO
Primary open-angle glaucoma (POAG) is a complex disorder characterized by a progressive and treatable degeneration of the optic nerve. TIGR/myocilin (MYOC) gene mutations are found in approximately 4% of all POAG patients. Populations with frequent founder effects, such as the French-Canadians, offer unique advantages to implement genetic testing for the disorder. To assess molecular diagnosis for POAG in this population, we determined the prevalence of TIGR/MYOC mutations in 384 unrelated glaucoma patients, 38 ocular hypertensive subjects and 18 affected families (180 patients). We further analyzed the clinical features associated with these variations. Nine coding sequence variants were defined as mutations causing mostly, but not exclusively, POAG. Four families segregated distinct mutations (Gly367Arg, Gln368Stop, Lys423Glu and Pro481Leu), while 14 unrelated glaucoma patients harbored six known mutations (Thr293Lys, Glu352Lys, Gly367Arg, Gln368Stop, Lys423Glu and Ala445Val) and two novel (Ala427Thr and Arg126Trp). The frequencies of these mutations were respectively 3.8% and 22.2% in the unrelated and family studies. The Gly367Arg and Lys423Glu variants caused the earliest ages at onset. When achievable, assessment of relatives of unrelated mutation carriers showed the Arg126Trp and Gly367Arg to be familial. Characteristic allele signatures, indicative of specific founder effects, were observed for five of the six mutations conveyed by at least two patients. Recombination probability estimates suggested that the French-Canadian population had most probably inherited these six mutations from 7-10 Québec settlers. Our data demonstrated that genetic screening for TIGR/MYOC mutations should be offered to glaucoma families and to close relatives of unrelated patients aware of a family history for the disorder.