RESUMO
BACKGROUND: Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. METHODS: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. RESULTS: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. CONCLUSIONS: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.
Assuntos
Dermatologia , Internato e Residência , Humanos , Dermatologia/educação , Seleção de PessoalAssuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Quimiocina CCL20/metabolismo , Interleucina-17/metabolismo , Pitiríase Rubra Pilar/imunologia , Pele/patologia , Adulto , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Pitiríase Rubra Pilar/tratamento farmacológico , ProteômicaAssuntos
Melanoma/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Nevo com Halo/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Family history of melanoma is a major melanoma risk factor. However, self-reported family histories for some cancers, including melanoma, are commonly inaccurate. We used a unique database, the Utah Population Database (UPDB), as well as the Utah Cancer Registry to determine the accuracy of self-reported family history of melanoma in a large cohort of high-risk patients. Patient charts were reviewed and compared to records in the UPDB and the UCR to confirm personal and family history of melanoma in 1780 patients enrolled in a total body photography monitoring program. Self-reported family history of melanoma in first-degree relatives had an overall sensitivity of 71%, specificity of 79%, PPV of 31%, and NPV of 95%, with decreased accuracy (PPV) for second-degree relatives. A personal history of melanoma was the only factor significantly associated with accuracy in self-reported family history of melanoma. Patient age, sex, estimated nevus count, and number of prior personal melanomas were not significant predictors. Dermatologists should educate patients on the differences between melanomas, keratinocyte carcinomas, and pre-cancers. Confirming self-reported family history of melanoma may improve risk assessment for patients undergoing screening.
Assuntos
Saúde da Família , Melanoma/genética , Autorrelato/normas , Neoplasias Cutâneas/genética , Adulto , Fatores Etários , Confiabilidade dos Dados , Bases de Dados Factuais , Características da Família , Feminino , Humanos , Modelos Logísticos , Masculino , Prontuários Médicos , Melanoma/patologia , Sistema de Registros , Sensibilidade e Especificidade , Fatores Sexuais , Neoplasias Cutâneas/patologia , UtahRESUMO
Importance: Pityriasis rubra pilaris is a rare and disabling cutaneous disease that is frequently recalcitrant to conventional therapies and appears to involve interleukin (IL)-17 overexpression. Objective: To investigate the clinical response and safety of ixekizumab in treating pityriasis rubra pilaris. Design, Setting, and Participants: Single-arm, investigator-initiated trial conducted in adult patients with moderate to severe pityriasis rubra pilaris at a single-center academic university from June 2018 to January 2020. A total of 41 patients were screened, 12 were enrolled, and 11 completed the full duration of therapy. A referred, consecutive sample was used during participant selection. The treatment period and primary outcome occurred over 24 weeks with additional patient follow-up through 36 weeks. Intervention: Subcutaneous administration of ixekizumab, a humanized IgG4 antibody that binds IL-17A, at the US Food and Drug Administration-approved dosing schedule for treatment of psoriasis for 24 weeks. Main Outcomes and Measures: The primary outcome was the mean change in Psoriasis Area and Severity Index at 24 weeks. Secondary outcomes included change in affected body surface area, quality of life, induction of sustained remission, and association of improvement with CARD14 genetic variations and cutaneous cytokine expression. Results: A total of 12 white patients (mean [SD] age, 49.8 [15.1] years; 8 male [67%]) were enrolled between June 2018 and April 2019, with 11 completing the full course of intervention. The mean (SEM) improvements in Psoriasis Area and Severity Index, affected body surface area, and Dermatology Life Quality Index were 15.2 (2.1) (P < .0001), 29.8% (9.3%) (P = .009), and 9.5 (2.5) (P = .004), respectively. The 4 participants with the most improvement in Psoriasis Area and Severity Index at week 24 stayed in remission at week 36 (defined as lack of increase in Psoriasis Area and Severity Index from week 24 through week 36), off therapy. Relative dermal IL-17A expression decreased by a 1.9 log-fold change. No participants had known pathogenic CARD14 variations. There were no serious adverse events. Conclusions and Relevance: In this single-armed trial, ixekizumab was associated with reduced clinical signs and symptoms of pityriasis rubra pilaris in a subset of patients, including those in whom other systemic therapies have failed. Trial Registration: ClinicalTrials.gov Identifier: NCT03485976.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Pitiríase Rubra Pilar/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Proteínas Adaptadoras de Sinalização CARD/genética , Análise Mutacional de DNA , Fármacos Dermatológicos/efeitos adversos , Feminino , Seguimentos , Mutação com Ganho de Função , Guanilato Ciclase/genética , Humanos , Interleucina-17/análise , Interleucina-17/antagonistas & inibidores , Interleucina-17/metabolismo , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Pitiríase Rubra Pilar/diagnóstico , Pitiríase Rubra Pilar/genética , Pitiríase Rubra Pilar/patologia , Qualidade de Vida , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Resultado do TratamentoRESUMO
Total body photography (TBP) facilitates early melanoma detection, but long-term outcomes have not been well studied. Our objectives were to examine melanoma diagnoses, role of TBP-associated follow-up visits, and survival in patients monitored by TBP. A total of 1955 patients meeting inclusion criteria received TBP from 2004-2013 at a single academic center. We compared the melanoma diagnoses and overall survival of 1253 patients with any follow-up visits (median, three visits; range, 1-18) and 702 patients with no follow-up visits. Use of TBP photographs influenced decision to biopsy 66 of 121 (54.5%) melanomas diagnosed after TBP. Lower invasive melanoma Breslow depth was significantly associated with having one or more follow-up visit (median, 0.83 vs 0.33 mm; P = .002) and photographic review (median, 0.31 vs 0.48 mm; P = 0.02). In multivariable analyses, greater overall survival was significantly associated with having one or more follow-up visit after TBP (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.14-0.91; P < 0.032) and having more than 100 nevi (HR, 0.37; 95% CI, 0.22-0.64; P = 0.004). Worse overall survival was significantly associated with increasing age (HR per year, 1.06; 95% CI, 1.04-1.08; P < 0.001) and male sex (HR, 2.65; 95% CI, 1.48-4.73; P = 0.001). Thus, monitoring by TBP was associated with subsequent melanoma diagnoses of lower stage and depth and greater overall survival.
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Detecção Precoce de Câncer/métodos , Melanoma/diagnóstico , Fotografação , Neoplasias Cutâneas/diagnóstico , Pele/diagnóstico por imagem , Conduta Expectante/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biópsia , Tomada de Decisão Clínica/métodos , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Pele/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Adulto JovemRESUMO
In the first article in this continuing medical education series we review controversies and uncertainties relating to the epidemiology and initial diagnosis of localized cutaneous melanoma (ie, stage 0, I, or II). Many of these issues are unsettled because of conflicting evidence. Melanoma incidence appears to be increasing, yet its basis has not been fully explained. Despite the advantages of early detection, the US Preventive Services Task Force does not recommend skin screening for the general population. Occasionally, biopsy specimens of melanoma will show histologic regression, but the prognostic importance of this phenomenon is uncertain. Some practitioners recommend obtaining a sentinel lymph node biopsy specimen for thin melanomas showing regression, although this histologic finding is not part of the staging system for thin melanomas. Our goal is to provide the clinician who cares for patients with (or at risk for) melanoma with up-to-date contextual knowledge to appreciate the multiple sides of each controversy so that they will be better informed to discuss these issues with their patients and their families.
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Melanoma/epidemiologia , Melanoma/patologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Detecção Precoce de Câncer , Humanos , Incidência , Regressão Neoplásica EspontâneaRESUMO
Hemangiomas are benign vascular neoplasms which arise in early adulthood. Herein we present a 79-year-old woman with a hemangioma of the lower flank masquerading as a cutaneous manifestation of a systemic fungal infection upon initial histological analysis. Decreased elastin and collagen within the lesion likely accounted for the clumping and splaying of the capillaries into "hyphae-like" structures. Loss of dermal elastic tissue and collagen apparently concentrated the capillary proliferation into an unusual morphology mimicking the hyphal structures. Through additional staining methods the lesion was confirmed to be an unusual presentation of a capillary hemangioma.
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Derme/patologia , Hemangioma Capilar/patologia , Micoses/diagnóstico , Neoplasias Cutâneas/patologia , Idoso , Atrofia/patologia , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Parede TorácicaRESUMO
BACKGROUND: Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated. METHODS: The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment. RESULTS: In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients. CONCLUSIONS: Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017;123:4800-7. © 2017 American Cancer Society.
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Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Seleção de Pacientes , Adulto , Biópsia por Agulha , Carcinoma Pulmonar de Células não Pequenas/terapia , Ensaios Clínicos como Assunto , Feminino , Humanos , Imuno-Histoquímica , Modelos Logísticos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
Extracranial metastasis of glioblastoma multiforme (GBM) is rare, but has recently been reported with increasing frequency. GBM metastases typically present after a biopsy or resection of the primary tumor. An otherwise healthy 54year-old woman presented with recurring pleural effusions originally believed to be from a primary lung malignancy. The patient subsequently experienced a generalized tonic clonic seizure and a right temporal brain mass was discovered. The patient later developed weakness and radiculopathy, and an extramedullary extradural mass spreading from C7 to T6 was discovered. She underwent resection of both central nervous system lesions as well as a lung biopsy, and all pathologic specimens were consistent with GBM. The case presented is unique in that the patient's initial symptoms were related to her metastasis. Furthermore, a purely epidural spread of GBM that respects the leptomeninges and intramedullary parenchyma is highly unusual.
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Neoplasias Encefálicas/patologia , Neoplasias Epidurais/secundário , Glioblastoma/patologia , Neoplasias Pulmonares/secundário , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Lung cancer is the leading cause of cancer mortality. Great advances in non-small cell lung cancer therapy have been seen in the last decade, beginning with the success in treating lung cancer harboring EGFR mutations and ALK-gene rearrangements. The potential of these biomarker-driven therapies has propelled research in biomarker targeted approaches to the forefront of lung cancer research. The successful development of immunotherapeutic agents targeting PD-L1 and PD-1 with an associated non-genomic biomarker has opened a new front in the effort for targeted approaches. Although early-phase lung cancer studies have hinted at the potential to use biomarkers to select patients for allocation to treatment in the conduct of clinical trials, data from late-phase studies have tempered expectations. The data leave unclear the wisdom of routinely restricting enrollment on lung cancer clinical trials to biomarker restricted populations, particularly non-genomic biomarkers.