Asunto(s)
Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Duración de la Terapia , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Resultado del Tratamiento , Factores de TiempoRESUMEN
OBJECTIVE: Mycoplasma genitalium (MG) infection accounts for 10-35% of non-gonococcal non-chlamydial (NGNC) urethritis. However, given that most people infected with MG do not develop symptoms and that antimicrobial resistance is increasing worldwide, there is no evidence of any benefits of screening asymptomatic individuals. We conducted this study to describe MG screening practices and outcomes at a French Sexually Transmitted Infections (STI) center in which MG testing was performed selectively and multiplex assays were not carried out [i.e., simultaneous screening for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and MG]. METHODS: A retrospective, observational, single-center study was conducted at the STI unit of Saint-Louis Hospital in Paris. The records of all patients undergoing MG testing from January 1st, 2017, to December 31st, 2018, were reviewed. The primary aim of the study was to describe and evaluate the proportion of MG-positive (MG+) patients among those tested. Secondary objectives were determination of the prevalence of MG+ status among symptomatic patients, risk factors associated with MG infection, and therapeutic modalities and efficacy. RESULTS: Two hundred and forty-nine patients underwent MG testing, 28 (11%) of whom were positive (MG+). The prevalence of MG+ status among symptomatic NGNC patients was 12%. HIV-positive (HIV+) status was significantly associated with MG+ status in univariate and multivariate analyses (Odds Ratio=7.3, 95% Confidence Interval 1.3-41.7; P=0.02). Twenty-three patients (85%) received antibiotics. Eighteen (67%) received azithromycin for 5 days, but 7 had clinical resistance. No quinolone resistance was reported. CONCLUSION: Despite unavailability of multiplex testing at our facility, which led to targeted-only screening for MG, its relatively high local prevalence is in keeping with what is generally observed at similar facilities across the world, where use of multiplex tests enables systematic screening for MG alongside NG and CT. This reinforces the current recommendations in Europe, France and the US against systematic MG testing or treatment in asymptomatic patients.
Asunto(s)
Infecciones por Mycoplasma , Mycoplasma genitalium , Enfermedades de Transmisión Sexual , Uretritis , Chlamydia trachomatis , Humanos , Infecciones por Mycoplasma/diagnóstico , Infecciones por Mycoplasma/tratamiento farmacológico , Infecciones por Mycoplasma/epidemiología , Neisseria gonorrhoeae , Prevalencia , Estudios Retrospectivos , Enfermedades de Transmisión Sexual/complicaciones , Uretritis/diagnósticoRESUMEN
PURPOSE: Dabrafenib plus trametinib combination has greatly improved survival in BRAFV600mut metastatic melanoma patients. However, data regarding the influence of pharmacokinetic markers in real-life patients are lacking. In this study, we aimed to explore dabrafenib and trametinib pharmacokinetic impact on progression-free survival (PFS), duration of response (DOR) or all grades treatment-related adverse events (ARAE) occurrence in routine care patients. METHODS: BRAFV600mut metastatic melanoma patients initiating standard doses of dabrafenib 150 mg BID plus trametinib 2 mg QD were included. Clinical data were collected via the French biobank MelBase, prospectively enrolling unresectable stage III or IV melanoma. Clinical response evaluation, ARAE reporting and dabrafenib and trametinib plasma quantification were performed. Association of individual Bayesian-estimated pharmacokinetic markers (AUC0-τ and Ctrough) and baseline clinical variables with DOR, PFS, clinical response, and ARAE was then assessed. RESULTS: Fifty patients (comprising 4 AJCC stage IIIc and 46 stage IV) were included. Median PFS reached 11.4 months, and overall response rate 70%. Fifty percent of patients experienced ARAE (G3 n = 10, G4 n = 0). In univariate analysis, median dabrafenib Ctrough within intermediate range was associated with a significantly higher PFS (HR [95% CI] = 0.41 [0.18; 0.91], p = 0.029) and DOR (HR [95% CI] = 0.39 [0.16; 0.94], p = 0.024), and association with DOR remained significant in multivariate analysis (HR [95% CI] = 0.34 [0.12; 0.95], p = 0.040). Trametinib pharmacokinetic markers were significantly higher in patients experiencing ARAE compared to patients without ARAE. CONCLUSION: In this study, exposure-efficacy and tolerance analysis highlighted the interest of therapeutic drug monitoring to optimize therapeutic management in BRAFV600mut metastatic melanoma patients based on trough concentrations of dabrafenib and trametinib.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Melanoma/tratamiento farmacológico , Proteínas Proto-Oncogénicas B-raf/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Área Bajo la Curva , Teorema de Bayes , Monitoreo de Drogas/métodos , Femenino , Humanos , Imidazoles/administración & dosificación , Masculino , Melanoma/genética , Melanoma/patología , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Oximas/administración & dosificación , Supervivencia sin Progresión , Estudios Prospectivos , Piridonas/administración & dosificación , Pirimidinonas/administración & dosificación , Resultado del TratamientoRESUMEN
Paget's disease (PD) denotes an initially intra-epidermal adenocarcinoma that can later invade the dermis and metastasise. Among the extramammary forms of PD (EMPD), penoscrotal presentations are rarer than the vulvar and perianal forms. Once diagnosis has been confirmed by histopathological examination, a search for associated neoplasia must be conducted, although penoscrotal EMPD is less frequently associated with underlying neoplasia than mammary PD (MPD). The associated cancer most often involves a neighbouring organ, with prostate cancer being the most common, or in some cases consists of underlying cutaneous adnexal tumours. First-line therapy consists of surgical excision. Alternatives to surgery (imiquimod, CO2 laser vaporisation, dynamic phototherapy) may be considered in certain cases.
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Adenocarcinoma , Neoplasias de la Mama , Enfermedad de Paget Extramamaria , Enfermedad de Paget Mamaria , Humanos , Masculino , Enfermedad de Paget Extramamaria/diagnóstico , Enfermedad de Paget Extramamaria/terapia , EscrotoRESUMEN
Actinic cheilitis is a premalignant condition that can progress to squamous cell carcinoma with a higher propensity for metastasis than cutaneous squamous cell carcinoma. Optimal treatment for actinic cheilitis has not been established, and evidence-based estimates of clinical cure in the dermatology literature are limited. Here, we review and synthesize outcome data published for patients with actinic cheilitis after treatment with various modalities. A systematic review was conducted in MEDLINE, Embase and the Cochrane library for English, French and German-language studies and references of included articles from inception to 20 January 2020. Studies were included if they reported on at least six patients with biopsy-proven actinic cheilitis. After quality appraisal, results of studies with the strongest methodology criteria were synthesized. 18 studies of 411 patients (published 1985 to 2016) were included. The majority of the studies were case series. Carbon dioxide laser ablation and vermilionectomy were associated with the most favourable outcomes with fewest recurrences. Chemical peel and photodynamic therapy were associated with higher recurrence. Adverse effects generally resolved in the weeks following treatment and cosmetic outcomes were favourable overall. In conclusion, there is a lack of high-quality comparative studies evaluating different treatment options for actinic cheilitis. The included publications used various outcome measures; however, the majority reported on the recently defined core outcome sets. These results suggest that both carbon dioxide laser ablation and vermilionectomy are effective treatments for actinic cheilitis. Prospective head-to-head studies are needed to compare these treatment modalities and to assess patient preferences.
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Carcinoma de Células Escamosas , Queilitis , Neoplasias Cutáneas , Queilitis/terapia , Humanos , Recurrencia Local de Neoplasia , Estudios ProspectivosAsunto(s)
Drogas en Investigación/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Anilidas/uso terapéutico , Antineoplásicos/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Ensayos Clínicos como Asunto , Drogas en Investigación/efectos adversos , Humanos , Terapia Molecular Dirigida , Piridinas/uso terapéutico , Neoplasias Cutáneas/genéticaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Clorhidrato de Bendamustina/administración & dosificación , Brentuximab Vedotina/administración & dosificación , Linfoma Cutáneo de Células T/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/efectos adversos , Brentuximab Vedotina/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neumonía por Pneumocystis/inducido químicamente , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/inmunología , Índice de Severidad de la Enfermedad , Piel/efectos de los fármacos , Piel/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
Dermatologists have many therapeutic options for the management of actinic keratoses (AK), in order to treat individual lesions or wider areas. Field cancerization is an area of sun-damaged skin, where visible and subclinical lesions co-exist, and is prone to the development of further AK lesions and sun-related skin cancers (SC). Treatments available are instrumental or medical. Resistance to treatment or atypical symptoms must lead to a biopsy for histological exam. Cryotherapy is the most frequently used method to destroy small or isolated AK, whereas photodynamic therapy (PDT), 5-fluoro-uracil (5-FU), imiquimod, ingenol mebutate and diclofenac are required for large, multiple lesions, and for the treatment of field cancerization. Side-effects of these therapies are essentially local, including pain, irritation, erythema, edema and scars. There is no randomized comparative study reviewing all these treatments, therefore physicians must also consider clinical characteristics, patient's compliance, side-effects and cost when treating AK. Medicoeconomic data of these treatments have been analyzed in several countries, and annual costs are estimated between 250 and 2 000 , with an uncertain cost-effective relation. Finally, beyond treatment of AK lesions, patients with AK are at high risk of developing SC, and must therefore have regular full-body examination, in order to be detected and treated precociously. © 2019 Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Kératoses actiniques : comprendre et traiter réalisé avec le soutien institutionnel de Galderma International.
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Queratosis Actínica/terapia , Antiinflamatorios no Esteroideos/uso terapéutico , Antineoplásicos/uso terapéutico , Análisis Costo-Beneficio , Crioterapia/efectos adversos , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Diclofenaco/uso terapéutico , Diterpenos/uso terapéutico , Electrocoagulación , Fluorouracilo/uso terapéutico , Humanos , Imiquimod/uso terapéutico , Terapia por Láser , Fotoquimioterapia/efectos adversosAsunto(s)
Cuidados Posteriores/métodos , Dermoscopía , Detección Precoz del Cáncer , Melanoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/patología , Melanoma/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Fotograbar , Estudios Retrospectivos , Piel/diagnóstico por imagen , Piel/patología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugíaAsunto(s)
Alopecia/etiología , Neoplasias de Cabeza y Cuello/complicaciones , Linfoma de Células B/complicaciones , Cuero Cabelludo , Neoplasias Cutáneas/complicaciones , Femenino , Folículo Piloso , Neoplasias de Cabeza y Cuello/patología , Humanos , Linfoma de Células B/patología , Masculino , Estudios Retrospectivos , Neoplasias Cutáneas/patologíaAsunto(s)
Micosis Fungoide/diagnóstico , Neoplasias Cutáneas/diagnóstico , Enfermedades de la Vulva/etiología , Anciano de 80 o más Años , Femenino , Humanos , Micosis Fungoide/complicaciones , Micosis Fungoide/patología , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/patología , Enfermedades de la Vulva/patologíaAsunto(s)
Micosis Fungoide/diagnóstico , Síndrome de Sézary/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias del Timo/diagnóstico , Anciano , Biopsia , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad , Micosis Fungoide/terapia , Tomografía de Emisión de Positrones , Síndrome de Sézary/terapia , Piel/patología , Neoplasias Cutáneas/terapia , Timo/diagnóstico por imagen , Timo/patología , Neoplasias del Timo/secundario , Neoplasias del Timo/terapiaAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Autoinmunidad/efectos de los fármacos , Síndrome de Sézary/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/farmacología , Antineoplásicos/farmacología , Femenino , Humanos , Persona de Mediana Edad , Receptores CCR4/antagonistas & inhibidores , Receptores CCR4/inmunología , Inducción de Remisión/métodos , Síndrome de Sézary/sangre , Síndrome de Sézary/inmunología , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Neutrophilic eccrine hidradenitis (NEH) is a rare neutrophilic dermatosis, first described in patients undergoing chemotherapy for a malignant haemopathy. It has polymorphous clinical features and the association of both clinical and histological features is necessary to make a diagnosis. We report the first two cases of NEH in patients treated with a BRAF inhibitor (BRAFi), either dabrafenib or vemurafenib, for a stage IV metastatic melanoma. Disseminated erythematous plaques associated with fever and polyarthralgia occurred early after the initiation of treatment and were badly tolerated. Histological analyses confirmed the diagnosis of NEH. Symptoms disappeared a few days after the cessation of treatment and introduction of topical steroids. The replacement of one BRAFi with another is a therapeutic alternative as it is not necessarily associated with a relapse of NEH. NEH can be added to the spectrum of neutrophilic dermatoses induced by BRAFis. It occurs earlier (3-4 days) than previously described drug-induced NEH (9-12 days) and may be an earlier stage of eccrine squamous syringometaplasia, which has already been reported in the context of BRAFi-treated patients.