Asunto(s)
Dermoscopía/métodos , Dermatosis Facial/diagnóstico , Peca Melanótica de Hutchinson/diagnóstico , Queratosis Seborreica/diagnóstico , Lentigo/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano , Envejecimiento/fisiología , Estudios de Cohortes , Diagnóstico Diferencial , Dermatosis Facial/epidemiología , Dermatosis Facial/patología , Evaluación Geriátrica , Humanos , Peca Melanótica de Hutchinson/patología , Peca Melanótica de Hutchinson/terapia , Incidencia , Queratosis Seborreica/epidemiología , Queratosis Seborreica/patología , Queratosis Seborreica/terapia , Lentigo/epidemiología , Lentigo/patología , Lentigo/terapia , Masculino , Persona de Mediana Edad , Medición de Riesgo , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , VeteranosRESUMEN
Importance: Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. Objective: To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. Design, Setting, and Participants: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Interventions: Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Main Outcomes and Measures: Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Results: Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed. Conclusions and Relevance: A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma. Trial Registration: clinicaltrials.gov Identifier: NCT00847912.
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Carcinoma Basocelular/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Quimioprevención/métodos , Fluorouracilo/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Administración Cutánea , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/mortalidad , Carcinoma Basocelular/prevención & control , Carcinoma Basocelular/cirugía , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/prevención & control , Carcinoma de Células Escamosas/cirugía , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cirugía de Mohs/métodos , Cirugía de Mohs/estadística & datos numéricos , Pronóstico , Medición de Riesgo , Crema para la Piel/uso terapéutico , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/prevención & control , Neoplasias Cutáneas/cirugía , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Fluorouracilo/administración & dosificación , Queratosis Actínica/tratamiento farmacológico , Lesiones Precancerosas/tratamiento farmacológico , Administración Cutánea , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Dermatosis Facial/tratamiento farmacológico , Dermatosis Facial/patología , Femenino , Estudios de Seguimiento , Humanos , Queratosis Actínica/patología , Masculino , Lesiones Precancerosas/patología , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del TratamientoAsunto(s)
Personal Militar , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/prevención & control , Protectores Solares , Rayos Ultravioleta/efectos adversos , Adulto , Campaña Afgana 2001- , Factores de Edad , Estudios Transversales , Femenino , Humanos , Guerra de Irak 2003-2011 , Masculino , Análisis Multivariante , Prevalencia , Análisis de Regresión , Medición de Riesgo , Factores Sexuales , Neoplasias Cutáneas/etiología , Quemadura Solar/etiología , Quemadura Solar/prevención & control , Factores de Tiempo , Veteranos/estadística & datos numéricos , Adulto JovenRESUMEN
IMPORTANCE: Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. OBJECTIVE: To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. DESIGN, SETTING, AND PARTICIPANTS: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. INTERVENTIONS: Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. MAIN OUTCOMES AND MEASURES: This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. RESULTS: The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P < .001) and for the overall study duration (P < .001). The fluorouracil group also had higher complete AK clearance rates (38% vs 17% at 6 months) and fewer spot treatments at 6-month intervals, at study visits, and in between study visits during the trial (P < .01 for all). The fluorouracil group took longer to require the first spot AK treatment (6.2 months) compared with the control group (6.0 months) (hazard ratio, 0.69; 95% CI, 0.60-0.79). The number of hypertrophic AKs was not different between the 2 groups overall (P = .60), although there were fewer hypertrophic AKs in the fluorouracil group at 6 months (0.23 vs 0.41) (P = .05). CONCLUSIONS AND RELEVANCE: Our results indicate that a single course of fluorouracil cream, 5%, effectively reduces AK counts and the need for spot treatments for longer than 2 years. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00847912.
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Fluorouracilo/administración & dosificación , Queratosis Actínica/tratamiento farmacológico , Piel/patología , Administración Tópica , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Queratosis Actínica/diagnóstico , Masculino , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
There have been many reports of mitochondrial DNA (mtDNA) mutations associated with human malignancies. We have observed allelic instability in UV-induced cutaneous tumors at the mt-Tr locus encoding the mitochondrial tRNA for arginine. We examined the effects of somatic alterations at this locus by modeling the change in a uniform nuclear background by generating cybrids harboring allelic variation at mt-Tr. We utilized the naturally occurring mtDNA variation at mt-Tr within the BALB/cJ (BALB) and C57BL/6J (B6) strains of Mus musculus to transfer their mitochondria into a mouse ρ(0) cell line that lacked its own mtDNA. The BALB haplotype containing the mt-Tr 9821insA allele produced significant changes in cellular respiration (resulting in lowered ATP production), but increased rates of cellular proliferation in cybrid cells. Furthermore, the mtDNA genotype associated with UV-induced tumors endowed the cybrid cells with a phenotype of resistance to UV-induced apoptosis and enhanced migration and invasion capabilities. These studies support a role for mtDNA changes in cancer.
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Desequilibrio Alélico , Transformación Celular Neoplásica/genética , ADN Mitocondrial/genética , Mitocondrias/genética , Alelos , Animales , Antioxidantes/metabolismo , Apoptosis/genética , Arginina/genética , Arginina/metabolismo , Línea Celular , Movimiento Celular/genética , Núcleo Celular/genética , Proliferación Celular , Respiración de la Célula/genética , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Sitios Genéticos , Variación Genética , Haplotipos/genética , Células Híbridas/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mutación/genética , Invasividad Neoplásica/genética , Fenotipo , ARN de Transferencia/genéticaRESUMEN
BACKGROUND: Sentinel lymph node (SLN) status is the greatest prognostic factor of morbidity in melanoma. D2-40 antibody specifically marks lymphatic endothelium and has been used for identifying lymphatic invasion (LI) in multiple cancers. OBJECTIVE: We sought to determine the relationship between melanoma lymphatic invasion (as detected using D2-40 on primary melanoma biopsies/excisions) and the presence or absence of melanoma in subsequent SLN biopsy. METHODS: We retrospectively evaluated LI using D2-40 on primary biopsies/excisions from patients with thin to intermediate thickness (Breslow thickness: ≤2.0 mm) melanomas, who underwent lymphatic mapping and SLN biopsy, and whose SLN status was known. Sixty-four cases met the criteria and were available for analysis. We analyzed patient age, patient sex, mitotic rate, ulceration, tumor depth, and D2-40 detected LI as predictors of SLN status. RESULTS: Lymphatic invasion detection increased from 3.1% using hematoxylin and eosin only to 21.9% using D2-40. Twelve of 14 patients with D2-40 LI were SLN positive (positive predictive value, 85.7%). D2-40 LI was detected in the primary biopsy specimen of 12 of 18 patients with a positive SLN (sensitivity 66.7%). Of 50 patients without D2-40 LI, 44 were SLN negative (negative predictive value, 88.0%). Of 46 SLN-negative patients, 44 did not have D2-40 LI (specificity, 95.7%). LIMITATIONS: Results are retrospective and limited to SLN biopsy performed at one institution. CONCLUSIONS: On univariate and multivariate analysis, D2-40-detected LI was the most significant predictor of SLN status. D2-40 antibody staining to detect lymphatic invasion should be incorporated in routine melanoma biopsy evaluation.
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Anticuerpos Monoclonales , Ganglios Linfáticos/patología , Melanoma/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela/métodosRESUMEN
The National Institutes of Health (NIH) classification of graft-versus-host disease (GVHD) is a significant improvement over prior classifications, and has prognostic implications. We hypothesized that the NIH classification of GVHD would predict the survival of patients with GVHD treated with extracorporeal photopheresis (ECP). Sixty-four patients with steroid refractory/dependent GVHD treated with ECP were studied. The 3-year overall survival (OS) was 36% (95% confidence interval [CI] 13-59). Progressive GVHD was seen in 39% of patients with any acute GVHD (aGVHD) (classic acute, recurrent acute, overlap) compared to 3% of patients with classic chronic GVHD (cGVHD) (P=.002). OS was superior for patients with classic cGVHD (median survival, not reached) compared to overlap GVHD (median survival, 395 days, 95% CI 101 to not reached) and aGVHD (delayed, recurrent or persistent) (median survival, 72 days, 95% CI 39-152). In univariate analyses, significant predictors of survival after ECP included GVHD subtype, bilirubin, platelet count, and steroid dose. In multivariate analyses overlap plus classic cGVHD was an independent prognostic feature predictive of superior survival (hazard ratio [HR] 0.34, 95% CI 0.14-0.8, p=.014). This study suggests that NIH classification can predict outcome after ECP for steroid refractory/dependent GVHD.
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Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/terapia , Fotoféresis , Enfermedad Aguda , Adulto , Anciano , Bilirrubina/sangre , Enfermedad Crónica , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/clasificación , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Sweet's syndrome is an acute febrile neutrophilic dermatosis marked by attacks of painful, plaque-forming inflammatory papules accompanied by fever, arthralgias, peripheral leukocytosis, a diffuse dermal neutrophilic infiltrate, and prompt resolution of symptoms and lesions with glucocorticoid therapy. There are many reports of drug-induced Sweet's syndrome to various medications including all- trans -retinoic acid, carbamazepine, hydralazine, levonorgestrel/ethinyl estradiol, minocycline, trimethoprim/sulfamethoxazole, and granulocyte colony-stimulating factor. We describe the first known case of Sweet's syndrome induced by pegfilgrastim, a pegylated form of granulocyte colony-stimulating factor with unique pharmacologic properties that may induce Sweet's syndrome in patients with no history of neutrophilic dermatoses associated with granulocyte colony-stimulating factor therapy.
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Vesícula/inducido químicamente , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Neutropenia/congénito , Síndrome de Sweet/inducido químicamente , Vesícula/tratamiento farmacológico , Filgrastim , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Neutropenia/tratamiento farmacológico , Neutrófilos/citología , Polietilenglicoles , Proteínas RecombinantesRESUMEN
Porphyria cutanea tarda (PCT) is associated with estrogen, certain medications, alcohol abuse, hepatitis viruses, and iron overload. Numerous studies have demonstrated an increased incidence of hepatitis C in patients with PCT; therefore, hepatitis screening should be routinely performed on these patients. On the other hand, although studies have long suspected hereditary hemochromatosis (HH) to be an underlying condition of PCT, many physicians have a low index of suspicion. Also, diagnosis of HH has been difficult until recently, when the gene mutation was identified. We present a case of a patient with PCT, hepatitis C, and alcoholism who was homozygous for the HH gene mutation.