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Research into molecular targets for drug development in melanoma is starting to bear fruit. Of the drugs tested to date in patients with metastatic melanoma, those that have cargado de http://www.actasdermo.org el 27/03/2016. Copia para uso personal, se prohibe la transmision de este documento por cualquier medio o formato. Molecular targets; BRAF; yielded the best results are V600E BRAF inhibitors in melanomas carrying the V600E mutation; ity inhibitors in melanomas carrying c-kit mutations; and antic-kit tyrosine kinase activ C-kit; Anti CTLA-4 cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, which block the mechanisms involved in immune tolerance. Many problems have yet to be resolved in these areas, however, such as the rapid development of resistance to BRAF and c-kit inhibitors and the lack of biomarkers to predict treatment response in the case of CTLA-4 blockers. We review the results of targeted Con posterioridad a la redaccion de este manuscrito, en julio de 2011, la Agencia Europea del Medicamento (EMA) aprobo Ipilimumab (Yervoy®) para el tratamiento del melanoma avanzado (metastasico o irresecable) resistente a, al menos, un tratamiento previo (ya aprobado por la FDA en marzo del 2011). En agosto del 2011, la FDA aprobo PLX4032 o Vemurafenib (Zelboraf®) como tratamiento de primera linea del melanoma metastasico y/o irresecable quirurgicamente. ∗ Autor para correspondencia. Correo electronico: marti@medicina.udl.cat (R.M. Marti). 0001-7310/$ – see front matter © 2011 Elsevier Espana, S.L. y AEDV. Todos los derechos reservados. 10.1016/j.ad.2011.08.009 580 R.M. Marti et al therapy with these and other drugs in metastatic melanoma and discuss what the future holds

Locoregional cutaneous metastases of melanoma (LCMM) represent a therapeutic challenge. Many treatment options are available with varying results. The combination of cryotherapy and imiquimod, two treatments with a possible synergistic effect, has not yet been described for treating this disease. In this paper, we aimed to show the response of LCMM to cryotherapy combined with topical imiquimod 5%. A retrospective review of 20 patients diagnosed with LCMM and treated with cryotherapy combined with topical imiquimod 5% between November 2000 and May 2014 at three institutions was performed. The locoregional cutaneous response was evaluated. After a mean of five sessions, 13 patients (65%) responded to treatment, eight (40%) of these completely and five (25%) partially. Systemic disease progressed in 16 (80%) patients. Cryotherapy followed by topical imiquimod 5% is simple to apply, has minimal adverse effects and provides response rates similar to other, more complex treatment options.

Los programas que se imparten en la mayoria de las facultades de medicina son de contenidos. Incluyen «lo que explicara el profesor» en forma de listado de temas, agrupados bajo una logica etiopatogenica o sindromica. Suelen seguir los contenidos de los libros de cada especialidad y se modifican cuando varian los horarios, el numero de creditos o para incluir los avances cientificos. La metodologia docente empleada consiste habitualmente en clases magistrales. Este tipo de ensenanza se fundamenta en los contenidos del informe Flexner1, que postulaba que la ensenanza teorica de la medicina era fundamental, que su objetivo esencial era proporcionar a los alumnos un solido fundamento cientifico, y que, por tanto, los profesores debian ser investigadores y las practicas clinicas habian de realizarse con pacientes ingresados en hospitales universitarios. La ensenanza tradicional aporta muchas ventajas. Proporciona seguridad porque se posee una amplia experiencia y parece que «no nos dejamos nada importante por explicar». Es aceptada por los alumnos, los profesores y las facultades. Por los alumnos porque si existen dudas las aclarara el propio profesor al final de la clase, el temario se reduce a los apuntes dictados y es un sistema adecuado para superar el examen MIR actual, ya que el nivel de los conocimientos teoricos que se obtiene es muy elevado. Por los profesores porque es facil de estructurar y proporciona una total independencia en la programacion de la asignatura, y por la facultad por cuanto supone un ahorro de tiempo y medios, ya que puede impartirse a grupos numerosos de alumnos. Tambien tiene inconvenientes. El protagonista de este modelo es el profesor, mientras que el estudiante es un sujeto pasivo que recibe las clases como un «listado de apuntes» a memorizar, por lo que la receptividad de la informacion es baja y la olvida con rapidez. La independencia tiene como contrapartida que los contenidos son inconexos con el resto de las asignaturas y a menudo son excesivos para un medico general. Se potencian poco el autoaprendizaje, el desarrollo de habilidades clinicas de comunicacion, de actitudes eticas y proporciona una escasa preparacion para resolver casos clinicos, con lo que no se estimula el mecanismo de razonamiento logico del medico frente a un paciente. Por otra parte, la formacion clinica en hospitales universitarios implica que los estudiantes se interesen por la alta tecnologia y los conocimientos cientificos mas recientes, y solo entran en contacto con una faceta de la medicina, la curacion de la enfermedad. Sin embargo, la mayoria de consultas en atencion primaria consistiran en trastornos funcionales, estados de ansiedad, enfermedades degenerativas de curso cronico, problemas derivados de viviendas en malas condiciones y la malnutricion2. Por tanto, lo que deberia potenciarse es la asistencia medica, la promocion de la salud y la prevencion de la enfermedad, como se recomienda en la Declaracion de Edimburgo de 19883.

Standard antineoplastic treatment for metastatic melanoma is ineffective in the large majority of patients. Therefore, alternative approaches need to be investigated. STI571 is a new antineoplastic compound, which selectively inhibits the tyrosine kinase activity of ABL, c-Kit and platelet-derived growth factor receptor (PDGFR). Melanoma may express all of these proteins. The aim of this study was to investigate whether STI571 inhibits the in-vitro growth of melanoma cells. Nineteen cell lines were obtained from four primary and 15 metastatic melanomas of cutaneous origin. The percentages of positive cells for the putative targets of STI571 were as follows: ABL, 41-100%; c-Kit, 8-97%; PDGFR-alpha, 41-98%; PDGFR-beta, 51-99%. 3-(4,5-Dimethylthiazol-yl)-2,5-diphenyltetrazolium (MTT) and viability assays showed that STI571 clearly inhibits the proliferation of eight of the 19 (42.1%) cell lines. No relationship could be established between the expression of c-Kit, ABL, PDGFR-alpha or PDGFR-beta and the response of cell lines to STI571. Our study shows, for the first time, an antiproliferative effect of STI571 on human melanoma cell lines of cutaneous origin, raising the possibility of the future clinical use of STI571. The identification of the target of STI571 in human cutaneous melanoma cells would allow the selection of patients who could benefit from this treatment.

We present a case of Sweet's syndrome with atypical lesions, characterized by erythematous plaques, vesicles and bullous lesions. Skin lesions in patients with an underlying malignancy are more frequently atypical and with vesicular, bullous or even ulcerative characteristics, in addition to the typical plaques and nodules. However, the case presented is not associated with malignancy, despite the fact that these processes, particularly hematologic ones, should be suspected.

Paraneoplastic pemphigus is a life-threatening autoimmune bullous disease associated with neoplasia, generally of lymphoid origin. Immunosuppressive therapy is often disappointing and there are only a few reports of patients surviving more than 2 years. These cases were generally associated with benign neoplasms. We report here the case of a patient with paraneoplastic pemphigus associated with non-Hodgkin B-cell lymphoma who had a surprisingly good response to systemic corticosteroids and remains free of lesions more than 3 years later despite progression of her neoplasm.

We present a case of Sweet's syndrome with atypical lesions, characterized by erythematous plaques, vesicles and bullous lesions. Skin lesions in patients with an underlying malignancy are more frequently atypical and with vesicular, bullous or even ulcerative characteristics, in addition to the typical plaques and nodules. However, the case presented is not associated with malignancy, despite the fact that these processes, particularly hematologic ones, should be suspected.

Population aging in developed countries brings an increased prevalence of chronic disease and of polymedication-patients with several prescribed types of medication. Attention to chronic, polymedicated patients is a priority for its high cost and the associated risks, and tools for analyzing, understanding, and managing this reality are becoming necessary. We describe a prototype of a system for discovering, analyzing, and visualizing the co-occurrence of diagnostics, interventions, and medication prescriptions in a large patient database. The final tool is intended to be used both by health managers and planners and for primary care clinicians in direct contact with patients (for example for detecting unusual disease patterns and incorrect or missing medication). At the core of the analysis module there is a representation of diagnostics and medications as a hypergraph, and the most crucial functionalities rely on hypergraph transversal/variants of association rule discovery methods, with particular emphasis on discovering surprising or alarming combinations. The test database comes from the primary care system in the area of Barcelona for 2013, with over 1.6 million potential patients and almost 20 million diagnostics and prescriptions.