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1.
J Am Acad Dermatol ; 68(4): 560-567, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23182069

RESUMO

BACKGROUND: A minority of patients with T1 melanoma will have a positive sentinel lymph node (SLN) biopsy (SLNB) finding. Identifying who will develop metastatic disease is important in determining prognosis and treatment. OBJECTIVE: We sought to identify clinical and histologic features predictive of a positive SLNB result and determine its prognostic significance in patients with T1 melanoma. METHODS: Clinical and histologic parameters were evaluated in 484 patients with T1 melanoma for their ability to predict a positive SLNB result. The impact of various factors on SLN positivity was evaluated. SLN status was examined as a predictor of overall survival. RESULTS: In all, 34 patients had a positive SLNB finding. Four factors predicted a higher risk of SLN positivity: age 43 years or younger, Breslow depth 0.8 mm or greater, tumors on the lower extremity and trunk, and tumor-infiltrating lymphocyte level. By multivariate analysis, low tumor-infiltrating lymphocytes (P = .0015) and decreasing age (P = .0058) independently predicted SLN positivity. If 0 to 2 of these factors were present, the rate of a positive SLNB result was 3%; this increased to 15% with 3 factors present and to 30% if all 4 factors were present (P < .002). SLN-positive patients had significantly decreased survival (P = .003), and SLN status was the most powerful predictor of survival (P = .009). LIMITATIONS: Our data analysis includes patients from 1994 to 2007 and therefore information on mitotic rate, a recently defined T1b criterion, is not recorded for all patients. CONCLUSIONS: Combining clinical and histologic prognostic factors may help identify subgroups of T1 patients at higher risk of SLN positivity. SLN status has significant prognostic impact in patients with thin melanomas.


Assuntos
Melanoma/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Adulto , Feminino , Humanos , Masculino , Prognóstico
4.
Cutis ; 86(3): 133-5, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21049729

RESUMO

Rituximab is a B-cell depleting monoclonal antibody targeting CD20. Data concerning the behavior of psoriatic disease following rituximab therapy are extremely limited. In this report, the clinical course of a patient with established psoriasis who received rituximab therapy for vasculitis associated with mixed cryoglobulinemia (MC) type II is described. In addition to marked improvement in MC manifestations, modest improvement in psoriatic lesions also was observed following therapy. The literature concerning B-cell depletion in the setting of psoriatic disease is briefly reviewed.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Crioglobulinemia/tratamento farmacológico , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Murinos/farmacologia , Linfócitos B/imunologia , Crioglobulinemia/complicações , Humanos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Psoríase/complicações , Rituximab , Resultado do Tratamento , Vasculite/tratamento farmacológico , Vasculite/etiologia
5.
JAMA Dermatol ; 156(9): 1004-1011, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32725204

RESUMO

Importance: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care. Objective: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies. Evidence Review: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed. Findings: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility. Conclusions and Relevance: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.


Assuntos
Tomada de Decisão Clínica/métodos , Perfilação da Expressão Gênica/normas , Melanoma/diagnóstico , Guias de Prática Clínica como Assunto , Neoplasias Cutâneas/diagnóstico , Consenso , Conferências de Consenso como Assunto , Humanos , Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Estadiamento de Neoplasias , Prognóstico , Biópsia de Linfonodo Sentinela/normas , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
6.
Oncologist ; 14(10): 995-1002, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19776094

RESUMO

BACKGROUND: With no U.S. Food and Drug Administration-approved standard therapy other than high-dose interleukin-2 and dacarbazine for metastatic melanoma, biochemotherapy has shown promise, with long-term survival in selected patients. We felt that the study of prognostic factors would determine which patients might benefit from this intensive therapy. METHODS: One hundred thirty-five consecutive patients with metastatic melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy over 5 years were retrospectively studied to determine the most important prognostic factors for both overall survival and progression-free survival. RESULTS: The median overall survival (OS) time was 16.6 months, with 1-year and 5-year survival rates of 70% and 28%, respectively. The median progression-free survival (PFS) time was 7.6 months, with 15% of patients progression free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS, a performance status score of zero, normal lactate dehydrogenase (LDH) level, stage M1a, and nonvisceral sites of metastasis were favorable factors. The group with normal LDH levels and skin or nodes as one of their metastatic sites had a relatively good prognosis, with median survival time of 44 months and an estimated 5-year survival rate of 38%. Conversely, patients with an elevated LDH level without any skin or nodal metastases had a poor prognosis, with no long-term survivors. CONCLUSIONS: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy who have either a normal LDH level or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoterapia , L-Lactato Desidrogenase/sangue , Melanoma/terapia , Neoplasias Cutâneas/terapia , Adolescente , Adulto , Idoso , Análise de Variância , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Interleucina-2/uso terapêutico , Masculino , Melanoma/sangue , Melanoma/mortalidade , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida , Adulto Jovem
7.
J Am Acad Dermatol ; 61(1): 123-5, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19539848

RESUMO

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a clinically heterogeneous entity, encompassing a variety of debilitating conditions that have in common inflammation of the skeletal system and skin. To date, there is a paucity of documented efficacious treatment options. We report a 48-year-old man with skeletal and cutaneous signs and symptoms who improved dramatically after treatment with a combination of isotretinoin and pamidronate. This report provides an alternative treatment regimen for SAPHO that addresses the possible underlying pathophysiology of this likely underdiagnosed syndrome.


Assuntos
Erupções Acneiformes/tratamento farmacológico , Difosfonatos/uso terapêutico , Hiperostose/tratamento farmacológico , Isotretinoína/uso terapêutico , Osteíte/tratamento farmacológico , Psoríase/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Sinovite/tratamento farmacológico , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Pamidronato , Síndrome
8.
Dermatol Online J ; 15(10): 14, 2009 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-19951632

RESUMO

Angiokeratomas are benign proliferations of dilated thin-walled blood vessels in the upper dermis with overlying epidermal hyperkeratosis. There are several clinical variants of angiokeratomas: 1. Fordyce: smooth reddish-purple papules on scrotum or vulva; 2. Mibelli: hyperkeratotic papules on fingers or toes, solitary, multiple, or circumscriptum (grouped papules usually on an extremity); 4. angiokeratoma corporis diffusum, widespread papules that are a manifestation of one of several inherited lysozomal storage diseases. Herein, we report a rare case of multiple angiokeratomas of Fordyce on the corona of the glans penis.


Assuntos
Angioceratoma/patologia , Neoplasias Penianas/patologia , Neoplasias Cutâneas/patologia , Humanos , Masculino , Pessoa de Meia-Idade
11.
Melanoma Manag ; 4(1): 13-37, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28758010

RESUMO

Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Force's 2016 Draft Recommendation Statement on skin cancer screening.

12.
Arch Dermatol ; 141(4): 507-9, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15837871

RESUMO

BACKGROUND: Actinic keratoses (AKs) are dysplastic epidermal lesions considered to be potential precursors of squamous cell carcinoma. Most AKs are diagnosed clinically and are rarely confirmed histologically. High interobserver variation exists among dermatologists for the diagnosis of AKs. Previous studies of the positive predictive value of the diagnosis of AKs have yielded rates as high as 94%. This study evaluates the rate at which histologic analysis confirms the clinical impression (positive predictive value) of AKs in patients with a history of skin cancer. OBSERVATIONS: Seventeen (74%) of 23 lesions with classic features of AKs, as determined by 3 dermatologists, were confirmed as AKs histologically. These were lesions that would ordinarily not be biopsied. Of the 6 misdiagnoses, 5 (83%) were skin cancer, most often squamous cell carcinoma. CONCLUSIONS: The positive predictive value of 74% for the diagnosis of AKs in this study is substantially lower than that of 2 previous studies, suggesting that physicians may be misdiagnosing many patients with classic features of AKs. Most misdiagnosed cases were forms of skin cancer. These preliminary data suggest that the threshold for biopsy of suspect lesions in patients with a history of skin cancer should be low and warrant further evaluation.


Assuntos
Ceratose/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Adulto , Distribuição por Idade , Idoso , Biópsia por Agulha , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Incidência , Ceratose/diagnóstico , Ceratose/epidemiologia , Ceratose/cirurgia , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Medição de Risco , Sensibilidade e Especificidade , Distribuição por Sexo , Neoplasias Cutâneas/epidemiologia
13.
JAMA Dermatol ; 151(2): 212-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25409291

RESUMO

IMPORTANCE: The management of clinically atypical nevi/dysplastic nevi (CAN/DN) is controversial, with few data to guide the process. Management recommendations for DN with positive histologic margins were developed by the Delphi method to achieve consensus among members of the Pigmented Lesion Subcommittee (PLS) of the Melanoma Prevention Working Group (MPWG) after reviewing the current evidence. OBJECTIVES: To outline key issues related to the management of CAN/DN: (1) biopsies of CAN and how positive margins arise, (2) whether incompletely excised DN evolve into melanoma, (3) current data on the outcomes of DN with positive histologic margins, (4) consensus recommendations, and (5) a proposal for future studies, including a large-scale study to help guide the management of DN with positive margins. EVIDENCE REVIEW: The literature, including recent studies examining management and outcomes of DN with positive margins between 2009 to 2014, was reviewed. FINDINGS: A consensus statement by the PLS of the MPWG following review of the literature, group discussions, and a structured Delphi method consensus. CONCLUSIONS AND RELEVANCE: This consensus statement reviews the complexities of management of CAN/DN. A review of the literature and 2 rounds of a structured Delphi consensus resulted in the following recommendations: (1) mildly and moderately DN with clear margins do not need to be reexcised, (2) mildly DN biopsied with positive histologic margins without clinical residual pigmentation may be safely observed rather than reexcised, and (3) observation may be a reasonable option for management of moderately DN with positive histologic margins without clinically apparent residual pigmentation; however, more data are needed to make definitive recommendations in this clinical scenario.


Assuntos
Consenso , Procedimentos Cirúrgicos Dermatológicos/normas , Gerenciamento Clínico , Síndrome do Nevo Displásico/cirurgia , Melanoma/cirurgia , Guias de Prática Clínica como Assunto , Neoplasias Cutâneas/cirurgia , Humanos
16.
J Biomed Opt ; 17(7): 076014, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22894497

RESUMO

Optimal treatment of skin cancer before it metastasizes critically depends on early diagnosis and treatment. Imaging spectroscopy and polarized remittance have been utilized in the past for diagnostic purposes, but valuable information can be also obtained from the analysis of skin roughness. For this purpose, we have developed an out-of-plane hemispherical Stokes imaging polarimeter designed to monitor potential skin neoplasia based on a roughness assessment of the epidermis. The system was utilized to study the rough surface scattering for wax samples and human skin. The scattering by rough skin-simulating phantoms showed behavior that is reasonably described by a facet scattering model. Clinical tests were conducted on patients grouped as follows: benign nevi, melanocytic nevus, melanoma, and normal skin. Images were captured and analyzed, and polarization properties are presented in terms of the principal angle of the polarization ellipse and the degree of polarization. In the former case, there is separation between different groups of patients for some incidence azimuth angles. In the latter, separation between different skin samples for various incidence azimuth angles is observed.


Assuntos
Polarimetria de Varredura a Laser/instrumentação , Polarimetria de Varredura a Laser/métodos , Neoplasias Cutâneas/patologia , Análise Espectral Raman/instrumentação , Análise Espectral Raman/métodos , Diagnóstico Precoce , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Exp Cell Res ; 276(2): 185-93, 2002 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-12027448

RESUMO

Telomeres are tandem repeats of a specific TTAGGG nucleotide sequence at the ends of chromosomes. Telomere shortening is proposed to act as a biological clock and cancer prevention mechanism by inducing a nonproliferative, senescent phenotype after a limited number of cellular divisions. Recent evidence also suggests that telomere disruption can trigger apoptosis in certain cell types, mimicking a major cellular response to DNA damage. Here, we show that addition of DNA oligonucleotides homologous to the telomere 3' overhang sequence causes lymphocytic (Jurkat) cells to undergo apoptosis, as described for lymphocytes following telomere loop disruption. We further implicate the p53 tumor suppressor and transcription factor, as well as the p53 homolog p73 and the E2F1 transcription factor, in mediating the apoptotic response. We propose that exposure of the telomere 3' overhang due to opening of the normal telomere loop structure is a physiologic signal for these DNA damage-like responses in vivo and that oligonucleotides partially or completely homologous to the telomere overhang mimic this signal in the absence of DNA damage or telomere disruption.


Assuntos
Região 3'-Flanqueadora/genética , Apoptose/genética , Proteínas de Ciclo Celular , Divisão Celular/genética , Senescência Celular/genética , DNA/genética , Células Eucarióticas/metabolismo , Telômero/genética , Região 3'-Flanqueadora/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sequência de Bases/efeitos dos fármacos , Sequência de Bases/genética , Divisão Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Senescência Celular/efeitos dos fármacos , DNA/farmacologia , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , Proteínas de Ligação a DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta a Droga , Fatores de Transcrição E2F , Fator de Transcrição E2F1 , Células Eucarióticas/efeitos dos fármacos , Genes Supressores de Tumor , Humanos , Células Jurkat , Proteínas Nucleares/efeitos dos fármacos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Oligonucleotídeos/genética , Oligonucleotídeos/farmacologia , Fase S/efeitos dos fármacos , Fase S/genética , Telômero/efeitos dos fármacos , Telômero/metabolismo , Timidina/genética , Timidina/farmacologia , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Tumoral p73 , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
19.
Exp Dermatol ; 12(2): 145-52, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12702142

RESUMO

The production of immunomodulatory cytokines such as interleukin-10 (IL-10) from keratinocytes and other target cells in the skin plays a crucial role in UV-induced immunosuppression. Substantial evidence supports an association between DNA damage and immunomodulation. It is also known that small DNA fragments such as thymidine dinucleotides (pTpT) can mimic several UV-induced effects, including inhibition of the induction phase of the contact hypersensitivity response and up-regulation of tumor necrosis factor-alpha (TNF-alpha). To determine whether pTpT also induces IL-10 secretion by keratinocytes, and by inference whether IL-10 production after UV irradiation is a response to DNA damage, we compared the effects of pTpT with those of UV irradiation on primary human keratinocyte cultures. Subconfluent cultures of primary human keratinocytes were treated either with 10 micro M or 100 micro M pTpT or diluent alone, or exposed to solar-simulated light (100 J/m2 of UVB) or sham irradiated. An increase in IL-10 mRNA expression was observed 6-24 h after irradiation and at 24-48 h after treatment with pTpT. Detection of secreted IL-10 protein coincided with up-regulation of IL-10 gene expression at 48 and 72 h as determined by ELISA. Conditioned media from human keratinocytes treated with pTpT, like that from irradiated cells, significantly inhibited lymphocyte proliferation in the allogeneic-mixed lymphocyte reaction (MLR) assay. To determine whether pTpT mimics the suppressive influence of UVB on the elicitation phase of contact hypersensitivity, believed to result largely from IL-10 release, we compared the effects of topical application of pTpT with those of UVB irradiation on C57Bl/6 mice sensitized with dinitrofluorobenzene. Sensitized mice treated with pTpT or UVB irradiation showed markedly suppressed elicitation of ear-swelling responses. These results demonstrate that increased keratinocyte IL-10 mRNA level and IL-10 protein release are among the effects of pTpT and support the hypothesis that pTpT treatment triggers many of the biologic effects of UV irradiation by mimicking UV-induced DNA damage. Finally, regardless of mechanism, the data suggest that topical treatment with pTpT may provide a novel means of suppressing contact hypersensitivity or other lymphocyte-mediated reactions in skin.


Assuntos
Dermatite de Contato/prevenção & controle , Interleucina-10/biossíntese , Interleucina-10/genética , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Oligodesoxirribonucleotídeos/farmacologia , Animais , Células Cultivadas , Dano ao DNA , Dermatite de Contato/genética , Dermatite de Contato/imunologia , Expressão Gênica/efeitos dos fármacos , Humanos , Queratinócitos/efeitos da radiação , Teste de Cultura Mista de Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Raios Ultravioleta
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