Mostrando entradas con la etiqueta malvehy. Mostrar todas las entradas
Mostrando entradas con la etiqueta malvehy. Mostrar todas las entradas

jueves, 20 de febrero de 2020

Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with lentigo maligna melanoma in a Mediterranean population

https://doi.org/10.1111/bjd.12418

Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with lentigo maligna melanoma in a Mediterranean population

LINK:  https://doi.org/10.1111/bjd.12418


Funding sources The research at the Melanoma Unit in Barcelona was partially funded by Grants 03/0019, 05/0302, 06/0265 and 09/01393 from Fondo de Investigaciones Sanitarias, Spain; by the CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain; by the AGAUR 2009 SGR 1337 of the Catalan Government, Spain; by the European Commission under the 6th Framework Programme, contract no. LSHCCT2006018702 (GenoMEL) and by the National Cancer Institute of the U.S. National Institutes of Health (CA83115). The work was carried out at the Esther Koplowitz Centre, Barcelona, Spain. The samples from the Instituto Valenciano de Oncología were collected from the Biobanco del Instituto Valenciano de Oncología.

Background

Cutaneous melanoma tumour is classified into clinicohistopathological subtypes that may be associated with different genetic and host factors. Variation in the MC1R gene is one of the main factors of risk variation in sporadic melanoma. The relationship between MC1R variants and the risk of developing a specific subtype of melanoma has not been previously explored.

Objectives


To analyse whether certain MC1R variants are associated with particular melanoma subtypes with specific clinicohistopathological features.

Methods


An association study was performed between MC1R gene variants and clinicopathological subtypes of primary melanoma derived from 1679 patients.

Results


We detected 53 MC1R variants (11 synonymous and 42 nonsynonymous). Recurrent nonsynonymous variants were p.V60L (30·0%), p.V92M (11·7%), p.D294H (9·4%), p.R151C (8·8%), p.R160W (6·2%), p.R163Q (4·2%) p.R142H (3·3%), p.I155T (3·8%), p.V122M (1·5%) and p.D84E (1·0%). Melanoma subtypes showed differences in the total number of MC1R variants (= 0·028) and the number of red hair colour variants (= 0·035). Furthermore, an association between p.R163Q and lentigo maligna melanoma was detected under a dominant model of heritance (odds ratio 2·16, 95% confidence interval 1·07–4·37; = 0·044). No association was found between p.R163Q and Fitzpatrick skin phototype, eye colour or skin colour, indicating that the association was independent of the role of MC1R in pigmentation. No association was observed between MC1R polymorphisms and other melanoma subtypes.

Conclusions


Our findings suggest that certain #MC1R variants could increase melanoma risk due to their impact on pathways other than pigmentation, and may therefore be linked to specific melanoma subtypes
 
#malvehy #susanapuig #cristinacarrera  #paulaaguilera #jmalvehy #melanoma #skincancer  #mc1r #genomel
J.A. PuigButillé C. Carrera R. Kumar Z. GarciaCasado P. Aguilera J. Malvehy E. Nagore S. Pui

 

miércoles, 27 de marzo de 2019

La difícil tarea de detectar la queratosis actínica

La alta prevalencia de la patología hace que esté infradiagnosticada, razón por la que la labor preventiva del farmacéutico se vuelve aún más relevante.

La #queratosisactínica es una lesión premaligna cada vez más frecuente en la oficina de farmacia. Una correcta exploración facilitará su identificación para tratarla, evitando así una posible derivación a cáncer cutáneo. Sobre ello hablarán Gema Herrerías, vocal de Dermofarmacia del COF de Sevilla, y  Josep Malvehy, director de la Unidad de Cáncer Cutáneo del Servicio de Dermatología del Hospital Clínico, de Barcelona, en una de las mesas redondas que están previstas en Infarma.
Se trata de “tumores cutáneos inducidos por la radiación ultravioleta que pueden progresar a carcinomas escamosos”, declara Malvehy a CF, y añade que “tendemos a hablar con el paciente de lesión premaligna para no alarmarlo”. Según cuenta, son pocos los tumores que pueden derivar en un cáncer, “sólo lo hacen cerca del 5 por ciento”. Sin embargo, la queratosis actínica se asocia a una piel dañada por la acción solar y, por tanto, “puede ser un marcador del cáncer de piel y precursora del mismo tiempo”.

El papel del farmacéutico en la queratosis actínica

Las lesiones poco intensas no son fáciles de identificar, a lo que se suma “el hecho de que existe una nula percepción de riesgo de esta enfermedad y que muchos pacientes las confunden con manchas de envejecimiento si no sangran o duelen”, apunta Herrerías. La vocal considera que el farmacéutico comunitario, al ser el profesional de salud más accesible, “tiene como responsabilidad promover campañas sanitarias informativas para su detección precoz”. Para que esto sea posible “debe haber una formación adecuada en el reconocimiento de las lesiones”.
Las manifestaciones cutáneas de la queratosis actínica se presentan como lesiones rosadas, rugosas, ásperas y escamosas”, expone el dermatólogo. Sus formas clínicas van desde lesiones atróficas, hipertróficas, pigmentadas y liquenoides hasta cuerno cutáneo. Pueden inflamarse produciendo dolor, en esos casos “los pacientes suelen pedir el tratamiento”.

Cuándo derivar

El principal criterio de derivación al médico es la presencia de una o múltiples lesiones en zonas fotoexpuestas, “como el dorso de la nariz, la frente, mejillas y las orejas”, menciona Herrerías. No obstante, “los hábitos de vestimenta y la diferente climatología entre zonas pueden modificar estas localizaciones”. El perfil de paciente es fundamentalmente varón, de edad avanzada, de piel blanca, calvo y cuya actividad laboral se ha desarrollado al aire libre.
En cuanto a las terapias son varias: quirúrgicas, destructivas (empleando microgenolíquido) y la fotodinámica, además de los fármacos tópicos de prescripción médica. El 5-fluorouracilo o el diclofenaco en gel son algunos de ellos.
La elección de uno u otro “dependerá de la gravedad y la extensión de las pápulas”, pero también se deben tener en cuenta otros factores, como la independencia del paciente para su aplicación o la tolerancia hacia los efectos secundarios. Otro factor que puede ser determinante en la elección y al que Malvehy da especial importancia es a “si son financiados y se pueden prescribir o no”.

Una patología infradiagnosticada

Ante la pregunta de si considera que es una enfermedad infradiagnosticada, el médico responde con un rotundo “sí”. Según explica, “el problema es que es muy prevalente y el volumen de recursos que puede requerir el diagnóstico y el tratamiento de todas las queratosis actínicas de la población es ingente. De hecho, seguramente sería inasumible”.
Por otro lado, augura que su incidencia seguirá aumentando en Europa durante las próximas décadas. La razón es, principalmente, “que se siguen dando exposiciones solares crónicas”; y, a pesar de la disposición de mejores herramientas para proteger la piel, “este aumento de casos no se va a modificar excesivamente”. Esto, continúa, “conduce a la necesitad de diseñar políticas de diagnóstico, tratamiento, prevención y educación para los próximos años, lo cual implica una mayor necesidad de recursos. Hablamos de una necesidad que debería verse cubierta para la poblacion”. Actualmente, al no ser así, “se priorizan aquellos casos de mayor gravedad y riesgo”, concluye.

Fotoprotección

Promover la fotoprotección, la fotoevitación y la autoexploración para evitar futuras lesiones es deber del farmacéutico, informa Herrerías. “Lo ideal es realizar esta labor durante el día a día de las dispensaciones en el mostrador”, concreta., aunque la labor fundamental consiste en potenciar la adherencia al tratamiento “informando de su correcta administración, posibles efectos secundarios y cuidados posteriores de las lesiones”.
Según Malvhey, “la fotorprotección es la piedra angular del tratamiento, por lo que en el caso de pacientes con fármacos fotosensibles “se debe advertir desde la farmacia que la fotoprotección ha de ser todavía mas estricta. Una vez el paciente comience a aplicar el filtro solar “notará una gran diferencia en sus pápulas”.

fuente: https://www.correofarmaceutico.com/autocuidado/la-dificil-tarea-de-detectar-la-queratosis-actinica.HTML

#josepmalvehy #queratosisactinica #gemaherrerias #fotoproteccion #infarma #queratosis #tratamientoqueratosisactinica #fotoenvejecimiento #diclofenaco

martes, 27 de marzo de 2018

AURKA Overexpression Is Driven by FOXM1 and MAPK/ERK Activation in Melanoma Cells Harboring BRAF or NRAS Mutations: Impact on Melanoma Prognosis and Therapy

AURKA Overexpression Is Driven by FOXM1 and MAPK/ERK Activation in Melanoma Cells Harboring BRAF or NRAS Mutations: Impact on Melanoma Prognosis and Therapy

Abstract

The cell cycle-related genes AURKA and FOXM1 are overexpressed in melanoma. We show here that AURKA overexpression is associated with poor prognosis in three independent cohorts of melanoma patients and correlates with the presence of genomic amplification of AURKA locus and BRAFV600E mutation. AURKA overexpression may also be driven by increased promoter activation through elements such as ETS and FOXM1 found within the 5' proximal promoter region. Activated MAPK/ERK signaling pathway mediates robust AURKA promoter activation, thereby knockdown of BRAFV600E and ERK inhibition results in reduced AURKA transcription and expression. We show a positive correlation between FOXM1 and AURKA expression in three independent cohorts of melanoma patients. FOXM1 silencing decreases expression of AURKA and late cell cycle genes in melanoma cells. We further found that FOXM1 expression levels are significantly higher in tumors carrying the BRAFV600E mutation compared with the wild-type BRAF (BRAFwt). Accordingly, the knockdown of BRAFV600E also reduces the expression of FOXM1 in BRAFV600E cells. Moreover, Aurora kinase A and FOXM1 inhibition by either genetic knockdown or pharmacologic inhibitors impair melanoma growth and survival both in culture and in vivo, underscoring their therapeutic value for melanoma patients who fail to benefit from BRAF/MEK signaling inhibition.

https://www.ncbi.nlm.nih.gov/pubmed/28188776


#mutationsmelanoma #melanoma #malvehy #josepmalvehy #skincancer #aurka #braf

jueves, 22 de marzo de 2018

Ugly Duckling Sign as a Major Factor of Efficiency in Melanoma Detection

Importance:

Understanding the contribution of the ugly duckling sign (a nevus that is obviously different from the others in a given individual) in intrapatient comparative analysis (IPCA) of nevi may help improve the detection of melanoma.

Objectives:

To assess the agreement of dermatologists on identification of the ugly duckling sign and estimate the contribution of IPCA to the diagnosis of melanoma.

Design, Setting, and Participants:

The same 2089 digital images of the nevi of a sample of 80 patients (mean age, 42 years [range, 19-80 years]; 33 men and 47 women), as well as 766 dermoscopic images from a subset of 30 patients (mean age, 40 years [range, 21-75 years]; 12 men and 18 women), were randomly presented to the same 9 dermatologists for blinded assessment from September 22, 2011, to April 1, 2013. The first experiment was designed to mimic an IPCA situation, with images of all nevi of each patient shown to the dermatologists, who were asked to identify ugly duckling nevi (UDN). The second experiment was designed to mimic a lesion-focused analysis to identify morphologically suspicious nevi. Data analysis was conducted from November 1, 2012, to June 1, 2013.

Main Outcomes and Measures:

Number of nevi labeled UDN and morphologically suspicious nevi, specificity of lesion-focused analysis and IPCA, and number of nevi identified for biopsy.

Results:

Of the 2089 clinical images of nevi from 80 patients (median number of nevi per patient, 26 [range, 8-81]) and 766 dermoscopic images (median number of nevi per patient, 19 [range, 8-81]), all melanomas were labeled UDN and as morphologically suspicious nevi by the 9 dermatologists. The median number of UDN detected per patient was 0.8 among the clinical images of nevi (mean, 1.0; range, 0.48-2.03) and 1.26 among the dermoscopic images (mean, 1.4; range, 1.00-2.06). The propensity to consider more or fewer nevi as having ugly duckling signs was independent of the presentation (clinical or dermoscopic). The agreement among the dermatologists regarding UDN was lower with dermoscopic images (mean pairwise agreement, 0.53 for clinical images and 0.50 for dermoscopic images). The specificity of IPCA was 0.96 for clinical images and 0.95 for dermoscopic images vs 0.88 and 0.85, respectively, for lesion-focused analysis. When both IPCA and lesion-focused analyses were used, the number of nevi considered for biopsy was reduced by a factor of 6.9 compared with lesion-focused analysis alone.

Conclusions and Relevance:

Intrapatient comparative analysis is of major importance to the effectiveness of the diagnosis of melanoma. Introducing IPCA using the ugly duckling sign in computer-assisted diagnosis systems would be expected to improve performance.

#josepmalvehy #clinicadermatologica #dermatologobarcelona #melanoma #cancerdepiel #diagnosismelanoma #canceruña #skincancer #dermatologabarcelona #bestdoctor #topdoctors #nevus #confocal #susanapuig

jueves, 15 de febrero de 2018

Ultrasound-based follow-up does not increase survival in early-stage melanoma patients: A comparative cohort study

PubMed

Ultrasound-based follow-up does not increase survival in early-stage melanoma patients: A comparative cohort study

https://www.ncbi.nlm.nih.gov/pubmed/28888850

INTRODUCTION:

Different protocols have been used to follow up melanoma patients in stage I-II. However, there is no consensus on the complementary tests that should be requested or the appropriate intervals between visits. Our aim is to compare an ultrasound-based follow-up with a clinical follow-up.

PATIENTS AND METHODS:

Analysis of two prospectively collected cohorts of melanoma patients in stage IB-IIA from two tertiary referral centres in Barcelona (clinical-based follow-up [C-FU]) and Turin (ultrasound-based follow-up [US-FU]). Kaplan-Meier curves were used to evaluate distant metastases-free survival (DMFS), disease-free interval (DFI), nodal metastases-free survival (NMFS) and melanoma-specific survival (MSS).

RESULTS:

A total of 1149 patients in the American Joint Committee on Cancer stage IB and IIA were included in this study, of which 554 subjects (48%) were enrolled for a C-FU, and 595 patients (52%) received a protocolised US-FU. The median age was 53.8 years (interquartile range [IQR] 41.5-65.2) with a median follow-up time of 4.14 years (IQR 1.2-7.6). During follow-up, 69 patients (12.5%) in C-FU and 72 patients (12.1%) in US-FU developed disease progression. Median time to relapse for the first metastatic site was 2.11 years (IQR 1.14-4.04) for skin metastases, 1.32 (IQR 0.57-3.29) for lymph node metastases and 2.84 (IQR 1.32-4.60) for distant metastases. The pattern of progression and the total proportion of metastases were not significantly different (P = .44) in the two centres. No difference in DFI, DMFS, NMFS and MSS was found between the two cohorts.

CONCLUSION:

Ultrasound-based follow-up does not increase the survival of melanoma patients in stage IB-IIA.



#melanoma #josepmalvehy #malvehy   #americanjointcommitteeoncancer #metastases, #susanapuig #aliciabarreiro  #cristinacarrera #skincancer #dermatologiabarcelona #dermatologobarcelona #centrodermatologico #dermatologicalcenter #topdoctors #aad18

viernes, 19 de enero de 2018

Seven Non-melanoma Features to Rule Out Facial Melanoma.

Seven Non-melanoma Features to Rule Out Facial Melanoma.

https://www.ncbi.nlm.nih.gov/pubmed/28761960

Abstract

Facial melanoma is difficult to diagnose and dermatoscopic features are often subtle. Dermatoscopic non-melanoma patterns may have a comparable diagnostic value. In this pilot study, facial lesions were collected retrospectively, resulting in a case set of 339 melanomas and 308 non-melanomas. Lesions were evaluated for the prevalence (> 50% of lesional surface) of 7 dermatoscopic non-melanoma features: scales, white follicles, erythema/reticular vessels, reticular and/or curved lines/fingerprints, structureless brown colour, sharp demarcation, and classic criteria of seborrhoeic keratosis. Melanomas had a lower number of non-melanoma patterns (p< 0.001). Scoring a lesion suspicious when no prevalent non-melanoma pattern is found resulted in a sensitivity of 88.5% and a specificity of 66.9% for the diagnosis of melanoma. Specificity was higher for solar lentigo (78.8%) and seborrhoeic keratosis (74.3%) and lower for actinic keratosis (61.4%) and lichenoid keratosis (25.6%). Evaluation of prevalent non-melanoma patterns can provide slightly lower sensitivity and higher specificity in detecting facial melanoma compared with already known malignant features.

#melanoma #malvehy #skincancer #dermatologobarcelona #cedilp #susanapuig #melanomas #dermatoscopic #diagnosisofmelanoma #lentigo

A practical guide to the handling and administration of talimogene laherparepvec in Europe.

A practical guide to the handling and administration of talimogene laherparepvec in Europe.

https://www.ncbi.nlm.nih.gov/pubmed/28814886

Abstract

Talimogene laherparepvec is a herpes simplex virus-1-based intralesional oncolytic immunotherapy and is the first oncolytic virus to be approved in Europe. It is indicated for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (stage IIIB, IIIC, and IVM1a) with no bone, brain, lung, or other visceral disease. Talimogene laherparepvec is a genetically modified viral therapy, and its handling needs special attention due to its deep freeze, cold-chain requirements, its potential for viral shedding, and its administration by direct intralesional injection. This review provides a practical overview of handling, storage, and administration procedures for this agent in Europe. Talimogene laherparepvec vials should be transported/stored frozen at a temperature of -90°C to -70°C, and once thawed, vials must not be refrozen. Universal precautions for preparation, administration, and handling should be followed to avoid accidental exposure. Health care providers should wear personal protective equipment, and materials that come into contact with talimogene laherparepvec should be disposed of in accordance with local institutional procedures. Individuals who are immunocompromised or pregnant should not prepare or administer this agent. Talimogene laherparepvec is administered by intralesional injection into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound. Treatment should be continued for ≥6 months. As with other immunotherapies, patients may experience an increase in the size of existing lesion(s) or the appearance of new lesions (ie, progression) prior to achieving a response ("pseudo-progression"). As several health care professionals (eg, physicians [dermatologists, surgeons, oncologists, radiologists], pharmacists, nurses) are involved in different stages of the process, there is a need for good interdisciplinary collaboration when using talimogene laherparepvec. Although there are specific requirements for this agent's storage, handling, administration, and disposal, these can be effectively managed in a real-world clinical setting through the implementation of training programs and straightforward standard operating procedures.

#melanoma #skincancer #confocal #malvehy #doctormalvehy #cedilp #cancerdepiel #talimogene
#dermatologiabarcelona #dermatologobarcelona #cancerdepielbarcelona