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1.
Acta Derm Venereol ; 104: adv26002, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38380975

RESUMO

Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.


Assuntos
Acne Vulgar , Doxiciclina , Adulto , Humanos , Feminino , Doxiciclina/efeitos adversos , Espironolactona/efeitos adversos , Qualidade de Vida , Estudos Prospectivos , Acne Vulgar/diagnóstico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/induzido quimicamente , Peróxido de Benzoíla/uso terapêutico , Resultado do Tratamento , Método Duplo-Cego
2.
J Eur Acad Dermatol Venereol ; 37(9): 1785-1791, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37114291

RESUMO

BACKGROUND: Lentigo maligna (LM) is a melanocytic proliferation occurring on photo-exposed skin that may progress to LM melanoma. Surgery is recommended as first-line treatment. Excision margins of 5-10 mm remain, without international consensus. Several studies have shown that imiquimod, an immunomodulator, induces LM regression. This study investigated the effect of imiquimod versus placebo in neoadjuvant settings. PATIENTS AND METHODS: We performed a prospective, randomized, multicentre, phase III clinical study. Patients were randomly assigned in 1:1 ratio to receive imiquimod or placebo for 4 weeks, followed by LM excision 4 weeks after the last application of imiquimod or placebo. The primary endpoint was extra-lesional excision, with a 5 mm margin from the residual pigmentation after imiquimod or vehicle. Secondary endpoints included the gain on the surface removed between the two groups; number of revision surgeries to obtain extra-lesional excisions; relapse-free time; and number of complete remissions after treatment. RESULTS: A total of 283 patients participated in this study; 247 patients, 121 patients in the placebo group and 126 in the imiquimod group, accounted for the modified ITT population. The first extralesional extirpation was performed in 116 (92%) imiquimod patients and in 102 (84%) placebo patients; the difference was not significant (p = 0.0743). Regarding the surface of LM, imiquimod reduced the LM surface (4.6-3.1 cm2 ) significantly (p < 0.001) more compared to the placebo (3.9-4.1 cm2 ). CONCLUSION: Imiquimod reduces the lentigo maligna surface after 1 month of treatment, without a higher risk of intralesional excision and with a positive aesthetic outcome.


Assuntos
Antineoplásicos , Sarda Melanótica de Hutchinson , Neoplasias Cutâneas , Humanos , Imiquimode/uso terapêutico , Sarda Melanótica de Hutchinson/tratamento farmacológico , Sarda Melanótica de Hutchinson/cirurgia , Antineoplásicos/uso terapêutico , Estudos Prospectivos , Aminoquinolinas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico
3.
Bioinformatics ; 37(15): 2165-2174, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-33523112

RESUMO

MOTIVATION: The principle of Breiman's random forest (RF) is to build and assemble complementary classification trees in a way that maximizes their variability. We propose a new type of random forest that disobeys Breiman's principles and involves building trees with no classification errors in very large quantities. We used a new type of decision tree that uses a neuron at each node as well as an in-innovative half Christmas tree structure. With these new RFs, we developed a score, based on a family of ten new statistical information criteria, called Nguyen information criteria (NICs), to evaluate the predictive qualities of features in three dimensions. RESULTS: The first NIC allowed the Akaike information criterion to be minimized more quickly than data obtained with the Gini index when the features were introduced in a logistic regression model. The selected features based on the NICScore showed a slight advantage compared to the support vector machines-recursive feature elimination (SVM-RFE) method. We demonstrate that the inclusion of artificial neurons in tree nodes allows a large number of classifiers in the same node to be taken into account simultaneously and results in perfect trees without classification errors. AVAILABILITY AND IMPLEMENTATION: The methods used to build the perfect trees in this article were implemented in the 'ROP' R package, archived at https://cran.r-project.org/web/packages/ROP/index.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

4.
J Am Acad Dermatol ; 86(5): 1042-1048, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33785385

RESUMO

BACKGROUND: Treatment of lentigo maligna (LM) is challenging because of the potential functional and esthetic surgical sequelae. Imiquimod has been proposed as a treatment for LM. Reflectance confocal microscopy (RCM) is a noninvasive method for the diagnosis of LM and margin assessment. OBJECTIVES: To compare the overall LM score (LMS) assessed by RCM before and 1 month after the start of imiquimod treatment compared to placebo and to define the immunohistochemical (IHC) profile of responders to imiquimod. METHODS: A controlled randomized study was conducted. Forty patients underwent RCM examination with calculation of the LMS at baseline and after 1 month of treatment. An IHC analysis of excised tissues was performed. RESULTS: The 1-month LMS was significantly lower in patients treated with imiquimod compared to those treated with placebo (P < .001). The criteria in the imiquimod-treated patients that demonstrated significant decrease were nonedged papillae; large, round pagetoid cells; atypical cells at the dermoepidermal junction; and follicular location of atypical cells. IHC analysis showed a higher level of interferon gamma in the resected specimens of patients responding to imiquimod (P = .04). LIMITATIONS: Sample size was small. CONCLUSION: Assessing the LMS by RCM was useful to monitor LM response to imiquimod accurately.


Assuntos
Sarda Melanótica de Hutchinson , Neoplasias Cutâneas , Dermoscopia/métodos , Humanos , Sarda Melanótica de Hutchinson/cirurgia , Imiquimode/uso terapêutico , Microscopia Confocal/métodos , Neoplasias Cutâneas/cirurgia
5.
Dermatology ; 238(3): 517-526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34818219

RESUMO

BACKGROUND: Targeted therapy is used to treat patients with a BRAF-mutated metastatic melanoma and is continued until disease progression or severe toxicity. No robust data on the management of patients achieving a complete remission (CR) are available. MAIN OBJECTIVE: To determine the relapse rate in the first year after targeted therapy discontinuation in patients in CR. SECONDARY OBJECTIVES: To determine the relapse rates throughout the follow-up and to identify prognostic factors for relapse at 1 year. METHODS: A retrospective, monocentric observational study was conducted in patients with advanced melanoma included in the RIC-Mel database who discontinued targeted therapy after achieving a CR confirmed by CT scan and PET/CT scan. RESULTS: Twenty-nine patients were included. Seventeen (58.6%) patients were treated with BRAF inhibitor (BRAFi) alone and 12 (41.4%) with a BRAFi combined with a MEK inhibitor (BRAFi + MEKi). The median treatment duration was 9.7 months. The relapse rates after discontinuation were 69% at 12 months (BRAFi: 70.6%; BRAFi + MEKi: 66.7%) and 76% at 36 months (BRAFi: 76.5%; BRAFi + MEKi: 75%). A non-significant trend towards a higher risk of relapse was found in women (p = 0.1; RR 3.36; 95% CI 0.77-17.07), in patients with an LDH level greater than the upper limits of normal (p = 0.58; RR 2.43; 95% CI 0.10-56.71), and when more than two metastatic sites were involved (p = 0.19; RR 4.6; 95% CI 0.46-46.51). After relapse, targeted therapy was resumed in 17 patients (7 with BRAFi; 10 with BRAFi + MEKi) with a response rate of 53%. CONCLUSIONS: This real-life study provided long-term data in patients who discontinued targeted therapy after CR. Most patients experienced a relapse in the first year after targeted therapy discontinuation, of whom 50% were in the first 3 months. After targeted therapy resumption, 53% of relapsing patients achieved an objective response. Patients should be followed during the first year after treatment discontinuation. In addition, patients with less than 3 metastatic sites, a baseline LDH level with normal ranges, men, and patients responding rapidly to treatment would be more likely to maintain a CR after treatment discontinuation.


Assuntos
Melanoma , Proteínas Proto-Oncogênicas B-raf , Feminino , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos
6.
Cancer Immunol Immunother ; 69(8): 1663-1672, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32306076

RESUMO

BACKGROUND: Adoptive tumor-infiltrating lymphocytes (TIL) therapy and interleukin-2 (IL-2) have been investigated in melanoma. AIM: To confirm previously observed preventive effects of TIL + IL2 in a subgroup of patients with relapsing metastatic stage III melanoma. METHODOLOGY: Open-label, randomized two-group, multicenter five-year trial in adult stage III melanoma patients with only one invaded lymph node after complete resection. Patients received TIL + IL2 or abstention. TIL + IL2 was administered within 8 weeks after lymph node resection and 4 weeks after. Disease-free survival was assessed every 2 months up to month 18, every 3 months up to month 36 and every 4 months up to 5 years. A once-a-year follow-up was scheduled beyond the five-year follow-up. Safety was assessed throughout the trial. RESULTS: Overall, 49 patients accounted for the modified intent-to-treat and 47 for the PP. Slightly more male than female patients participated; mean age was 57.7 ± 11.4 years in the TIL + IL2 group and 53.5 ± 13.0 years in the abstention group. After 5 years of follow-up, 11/26 patients in the TIL + IL2 group and 13/23 in the abstention group had relapsed. There was no statistical difference between the groups (HR: 0.63 CI 95% [0.28-1.41], p = 0.258), nine patients in the TIL + IL2 and 11 in the abstention group died with no significant difference between the two groups (HR: 0.65 CI95% [0.27 - 1.59], p = 0.34). Safety was good. CONCLUSION: We did not confirm results of a previous trial. However, ulceration of the primary melanoma may be considered predictive of the efficacy of TIL in melanoma in adjuvant setting, in a manner similar to interferon α.


Assuntos
Imunoterapia Adotiva/métodos , Interleucina-2/administração & dosagem , Linfonodos/imunologia , Linfócitos do Interstício Tumoral/imunologia , Melanoma/terapia , Recidiva Local de Neoplasia/terapia , Adjuvantes Imunológicos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Melanoma/imunologia , Melanoma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
7.
Neuromodulation ; 23(6): 789-795, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32725745

RESUMO

BACKGROUND: Occipital nerve stimulation (ONS) is shown to be effective in treating various forms of headache. Most studies describe the treatment of occipital neuralgia (ON), but in many patients, the clinical description could also correspond to cervicogenic headache (CGH) or occipital migraine (OM). These different entities (ON, CGH, and OM) may be grouped together under the term occipital headaches. OBJECTIVE: To assess the efficacy of ONS to treat occipital headaches in a large series of patients with a long-term follow-up. MATERIALS AND METHODS: We performed a retrospective review of data on 60 patients with intractable occipital headaches treated with occipital nerve stimulation (ONS), who were referred to our center between October 2008 and October 2014. Details of pain evaluation, location, duration, cause and previous treatment were analyzed. Evaluations included the visual analog scale (VAS), the number of headache days per month (NHD), and the Medication Quantification Scale (MQS). Trials with transcutaneous electrical nerve stimulation (TENS-ONS) were performed and served as a guide for surgery indication (see Patients and Method section). RESULTS: After one year of ONS, mean VAS had decreased from 8.4/10 to 2.8/10 (72.2% reduction [p < 0.001]), and 76% of patients had at least a 50% decrease in mean VAS score. The mean MQS score decreased from 18 to 8.8, corresponding to a reduction of pain medication by an average of 50%. Adverse events concerned 12 patients (20%). Six patients presented with electrode displacement or fracture (10%) and six patients presented with cases of infection (10%) associated with the pulse generator. CONCLUSIONS: The results of this large series confirm that ONS is an effective treatment option for patients with intractable occipital headaches, but the frequency of complications remains quite high and must be taken into account in the surgical decision.


Assuntos
Terapia por Estimulação Elétrica , Transtornos da Cefaleia , Transtornos da Cefaleia/terapia , Humanos , Nervos Periféricos , Estudos Retrospectivos , Resultado do Tratamento
8.
Exp Dermatol ; 27(6): 647-655, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29505109

RESUMO

Prognostic biomarkers for patients with melanoma after lymph node resection are of clinical relevance and could thus enable the identification of patients who therefore would most benefit from adjuvant treatment. The aim of this work was to determine, using an in vitro model, whether immune-related biomarkers, such as MHC-class I and II, melanoma-associated antigens, IDO1 and PD-L1, could also be relevant to predict the risk of relapse of patients with stage III melanoma after lymph node resection. We established tumor cell lines from metastatic lymph nodes of 50 patients with melanoma. The expression of investigated biomarkers was determined on untreated and IFN-γ treated melanoma cell lines using flow cytometry. Among the selected biomarkers, the IFN-γ-induced expression of PD-L1 and IDO1 was associated with an increased risk of relapse (P = .0001 and P = .013, respectively) and was also associated with death for IDO1 (P = .0005). In the future, this immunologic signature could permit the identification of patients at higher risk of relapse and justifying an adjuvant treatment using immunotherapy.


Assuntos
Antígenos de Neoplasias/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Melanoma/metabolismo , Proteínas de Membrana/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Adulto , Idoso , Antígeno B7-H1 , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Interferon gama/farmacologia , Metástase Linfática , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Cultura Primária de Células , Medição de Risco , Taxa de Sobrevida , Antígeno gp100 de Melanoma/metabolismo
9.
Acta Derm Venereol ; 98(2): 262-267, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29136261

RESUMO

Propionibacterium acnes, a major member of normal skin microbiota, is subdivided into 6 phylotypes: IA1, IA2, IB, IC, II and III. This study investigated P. acnes subgroups on the face and back in patients with severe acne and in healthy controls. In 71.4% of patients with severe acne, P. acnes phylotypes were identical on the face and back, whereas this was the case in only 45.5% of healthy controls. The healthy group carried phylotypes IA1 (39.1%) and II (43.4%), whereas the acne group carried a high predominance of IA1 (84.4%), especially on the back (95.6%). In addition, the single-locus sequence typing (SLST) method revealed A1 to be the predominant type on the back of patients with acne, compared with a wide diversity in the healthy group. We report here that severity of acne on the back is associated with loss of diversity of P. acnes phylotype, with a major predominance of phylotype IA1. The change in balance of cutaneous P. acnes subgroups might be an inducing factor in the activation of P. acnes, which could trigger inflammation.


Assuntos
Acne Vulgar/microbiologia , Filogenia , Propionibacterium acnes/classificação , Pele/microbiologia , Acne Vulgar/diagnóstico , Adolescente , Adulto , Dorso , Estudos de Casos e Controles , Face , Feminino , Genótipo , Humanos , Masculino , Propionibacterium acnes/genética , Propionibacterium acnes/isolamento & purificação , Índice de Gravidade de Doença , Adulto Jovem
10.
Acta Derm Venereol ; 98(4): 406-410, 2018 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-29327065

RESUMO

Nivolumab response rate is 40% in metastatic melanoma. Few studies have evaluated pre-treatment biomarkers predictive of response. The aim of this study was to identify potential peripheral blood biomarkers associated with survival in patients with advanced melanoma treated with nivolumab. All advanced melanoma cases treated with anti-programmed cell death protein 1 (anti-PD1) over a 3-year period in the Dermato-Oncology Department, Nantes, France were identified. For each case, 9 potential blood biomarkers were identified. Bivariate and multivariate analyses, adjusted for the American Joint Committee on Cancer (AJCC) classification stage, Eastern Cooperative Oncology Group (ECOG) performance status, lactate dehydrogenase (LDH) level and failure to respond to first-line therapy, were used to test the association between biomarkers and overall survival (primary outcome) or progression-free survival (secondary outcome). Increased monocyte count, leukocyte/lymphocyte ratio and neutrophil/lymphocyte ratio were significantly associated with decreased overall survival after bivariate and multivariate analyses. Increased monocyte count was also significantly associated with decreased progression-free survival. These blood variables are easily measured and could help to predict patient response before the introduction of anti-PD1 therapy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Farmacológicos/sangue , Biomarcadores Tumorais/sangue , Leucócitos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Proteína C-Reativa/metabolismo , Tomada de Decisão Clínica , Intervalo Livre de Doença , Feminino , França , Humanos , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Linfócitos , Masculino , Melanoma/sangue , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Monócitos , Análise Multivariada , Neutrófilos , Nivolumabe , Seleção de Pacientes , Projetos Piloto , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Fatores de Tempo , Resultado do Tratamento
11.
J Med Internet Res ; 20(4): e135, 2018 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-29653918

RESUMO

BACKGROUND: The early diagnosis of melanoma is associated with decreased mortality. The smartphone, with its apps and the possibility of sending photographs to a dermatologist, could improve the early diagnosis of melanoma. OBJECTIVE: The aim of our review was to report the evidence on (1) the diagnostic performance of automated smartphone apps and store-and-forward teledermatology via a smartphone in the early detection of melanoma, (2) the impact on the patient's medical-care course, and (3) the feasibility criteria (focusing on the modalities of picture taking, transfer of data, and time to get a reply). METHODS: We conducted a systematic search of PubMed for the period from January 1, 2007 (launch of the first smartphone) to November 1, 2017. RESULTS: The results of the 25 studies included 13 concentrated on store-and-forward teledermatology, and 12 analyzed automated smartphone apps. Store-and-forward teledermatology opens several new perspectives, such as it accelerates the care course (less than 10 days vs 80 days), and the related procedures were assessed in primary care populations. However, the concordance between the conclusion of a teledermatologist and the conclusion of a dermatologist who conducts a face-to-face examination depended on the study (the kappa coefficient range was .20 to .84, median κ=.60). The use of a dermoscope may improve the concordance (the kappa coefficient range was .29 to .87, median κ=.74). Regarding automated smartphone apps, the major concerns are the lack of assessment in clinical practice conditions, the lack of assessment in primary care populations, and their low sensitivity, ranging from 7% to 87% (median 69%). In this literature review, up to 20% of the photographs transmitted were of insufficient quality. The modalities of picture taking and encryption of the data were only partially reported. CONCLUSIONS: The use of store-and-forward teledermatology could improve access to a dermatology consultation by optimizing the care course. Our review confirmed the absence of evidence of the safety and efficacy of automated smartphone medical apps. Further research is required to determine quality criteria, as there was major variability among the studies.


Assuntos
Melanoma/diagnóstico , Smartphone/instrumentação , Telemedicina/métodos , Diagnóstico Precoce , Humanos
12.
JAMA ; 318(9): 816-824, 2017 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-28873160

RESUMO

Importance: Increasing participation in fecal screening tests is a major challenge in countries that have implemented colorectal cancer (CRC) screening programs. Objective: To determine whether providing general practitioners (GPs) a list of patients who are nonadherent to CRC screening enhances patient participation in fecal immunochemical testing (FIT). Design, Setting, and Participants: A 3-group, cluster-randomized study was conducted from July 14, 2015, to July 14, 2016, on the west coast of France, with GPs in 801 practices participating and involving adult patients (50-74 years) who were at average risk of CRC and not up-to-date with CRC screening. The final follow-up date was July 14, 2016. Interventions: General practitioners were randomly assigned to 1 of 3 groups: 496 received a list of patients who had not undergone CRC screening (patient-specific reminders group, 10 476 patients), 495 received a letter describing region-specific CRC screening adherence rates (generic reminders group, 10 606 patients), and 455 did not receive any reminders (usual care group, 10 147 patients). Main Outcomes and Measures: The primary end point was patient participation in CRC screening 1 year after the intervention. Results: Among 1482 randomized GPs (mean age, 53.4 years; 576 women [38.9%]), 1446 participated; of the 33 044 patients of these GPs (mean age, 59.7 years; 17 949 women [54.3%]), follow-up at 1 year was available for 31 229 (94.5%). At 1 year, 24.8% (95% CI, 23.4%-26.2%) of patients in the specific reminders group, 21.7% (95% CI, 20.5%-22.8%) in the generic reminders group, and 20.6% (95% CI, 19.3%-21.8%) in the usual care group participated in the FIT screening. The between-group differences were 3.1% (95% CI, 1.3%-5.0%) for the patient-specific reminders group vs the generic reminders group, 4.2% (95% CI, 2.3%-6.2%) for the patient-specific reminders group vs the usual care group, and 1.1% (95% CI, -0.6% to 2.8%) for generic reminders group vs the usual care group. Conclusions and Relevance: Providing French GPs caring for adults at average risk of CRC with a list of their patients who were not up-to-date with their CRC screening resulted in a small but significant increase in patient participation in FIT screening at 1 year compared with patients who received usual care. Providing GPs with generic reminders about regional rates of CRC screening did not increase screening rates compared with usual care. Trial Registration: clinicaltrials.gov Identifier: NCT02515344.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Clínicos Gerais , Sangue Oculto , Cooperação do Paciente , Detecção Precoce de Câncer/métodos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Classe Social
13.
Exp Dermatol ; 25(10): 783-8, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27194447

RESUMO

Circulating tumor DNA is a promising non-invasive tool for cancer monitoring. The main objective of our work was to investigate the relationship between mutant BRAF DNA in plasma and clinical response. Thirty-eight stage IV patients with a V600 mutated BRAF melanoma were included prior to any treatment. DNA was extracted from plasma and mutant DNA was detected using the amplification-refractory mutation system method. Before the beginning of any treatment, the corresponding BRAF mutation was detected in 29 of the 38 tested plasma samples (76.3% positive per cent agreement). We observed a strong correlation between the presence of circulating mutated DNA and overall survival (OS; P=.02), and with the number of metastatic sites (P=.01). The presence of circulating mutated DNA was also strongly correlated with serum LDH activity (P<.01) and S100 protein concentration (P<.01). Finally, seven patients presented discordant BRAF status in different tumor sites. In all these patients, the test performed on ctDNA was positive, suggesting that ctDNA analysis might be less sensitive to tumor heterogeneity. Altogether, these results suggest that plasmatic mutant BRAF DNA is a prognostic factor of OS, correlated with tumor burden. In addition, it represents an interesting alternative source of DNA to detect BRAF mutations before treatment.


Assuntos
DNA Tumoral Circulante/química , Melanoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Feminino , França/epidemiologia , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Melanoma/sangue , Melanoma/mortalidade , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas S100/sangue
14.
Scand J Prim Health Care ; 34(3): 286-94, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27467203

RESUMO

OBJECTIVE: The study objective was to measure the rates of inclusion of populations at risk of advanced melanoma in a pilot targeted screening project involving general practitioners. DESIGN: This cross-sectional database study compared the inclusion rates of patients who signed inclusion in a targeted screening project with those of patients who did not, during a period in which both groups of patients consulted investigators. SETTING: Data were extracted from the national healthcare insurance records in western France from 11 April to 30 October 2011. PATIENTS: Patients, older than 18, considered for the data extraction had consulted one of the 78 participating GPs during the study period, and were affiliated with the national healthcare insurance. MAIN OUTCOME MEASURES: Inclusion in the screening was the main outcome measure. Patients at risk of advanced melanoma were characterized by male gender, age over 50, low income, rural residence, farmer, and presence of chronic disease. RESULTS: A total of 57,279 patients consulted GPs during the inclusion period and 2711 (4.73%) were included in the targeted screening. Populations at risk of advanced melanoma were less included: men (OR = 0.67; 95%CI [0.61-0.73]; p < 0.001), older than 50 (OR = 0.67; 95%CI [0.60-0.74]; p < 0.001), low income (OR = 0.65; 95%CI [0.55-0.77]; p < 0.001), farmer (OR = 0.23; 95%CI [0.17-0.30]; p < 0.001) and presence of a chronic disease (OR = 0.87; 95%CI [0.77-0.98]; p < 0.028). CONCLUSION: This study demonstrated inequalities in the inclusion of patients in a melanoma screening. Patients at risk of advanced cancer were screened less often. Further studies should focus on GPs ability to identify and screen these patients. KEY POINTS Advanced melanoma is more frequently diagnosed in men, older patients and socioeconomically disadvantaged populations, which leads to survival inequalities. • Despite the involvement of general practitioners, the implementation of targeted melanoma screening did not avoid inclusion inequalities. • Men, older patients, patients suffering from chronic diseases, and low-income patients were less likely to benefit from screening. • The display of a conventional or an alarmist poster in the waiting room did not statistically reduce these inclusion inequalities.


Assuntos
Clínicos Gerais/educação , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Estudos Transversais , Feminino , França , Humanos , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Pôsteres como Assunto , Fatores de Risco , Distribuição por Sexo , Neoplasias Cutâneas/patologia , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
15.
Cancer Immunol Immunother ; 64(7): 805-15, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25846669

RESUMO

Tumor immune escape has recently been shown to be related to the development of an immune tolerance state of the microenvironment. Cytokines activating the immune system such as IFN-γ can be used to reverse the immune escape and thus to potentiate the efficacy of immunotherapy. A clinical study was conducted in 18 stage IIIc/IV melanoma patients treated with tumor-infiltrating lymphocytes (TILs) in combination with intratumoral TG1042 injection (adenovirus expressing IFN-γ). The primary objective was to investigate the safety of treatment. Secondary objectives were to study the clinical response and translational research. The treatment was well tolerated. Among the 13 patients evaluable for tumor response, 38.5% had an overall objective response (OOR = CR + PR) and disease control rate (DCR = CR + PR + S) of 46%. The clinical response of the 37 targeted lesions led to an OOR of 51% and a DCR of 75%. Translational research on predictive markers did not significantly differ between responder and non-responder patients. However, specifically regarding injected lesions, the clinical response correlated with CD3-/CD56+ NK cells which could be activated by TG1042. Further larger studies of this combined immunotherapy are needed to confirm our findings. Intralesional TG1042 combined with antigen-selected TILs should be discussed.


Assuntos
Interferon gama/uso terapêutico , Linfócitos do Interstício Tumoral/transplante , Melanoma/imunologia , Melanoma/terapia , Adenoviridae/genética , Adulto , Idoso , Linhagem Celular Tumoral , Terapia Baseada em Transplante de Células e Tecidos , Terapia Combinada/métodos , Feminino , GTP Fosfo-Hidrolases/genética , Terapia Genética/métodos , Humanos , Imunoterapia Adotiva/métodos , Interferon gama/genética , Linfócitos do Interstício Tumoral/imunologia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/genética , Evasão Tumoral/imunologia
17.
BJU Int ; 114(4): 522-31, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24112703

RESUMO

OBJECTIVE: To examine the extirpative quality of an open radical prostatectomy (RP) technique by first categorising and mapping all intraprostatic incisions into benign tissue and then determining a cumulative technical error rate given by all intraprostatic incisions into benign and malignant tissue. PATIENTS AND METHODS: We performed a retrospective review of prospectively collected data relating to 1065 men with clinically localised prostate cancer who underwent open retropubic RP (70.6% nerve-sparing surgery [NSS]) by a single surgeon (January 2005 to December 2011). We recorded all intraprostatic incisions: (i) iatrogenic positive surgical margins (PSMs), (ii) deep or superficial benign capsular incisions (BCIs), (iii) incisions into benign prostate glands at the prostate apex or bladder neck (benign glandular tissue incisions [BGTIs]), and determined incision location, length and nature (solitary/multiple). We evaluated: (i) associations between benign incisions, NSS and PSMs, (ii) significant predictors for PSM risk by multivariate analysis, (iii) postoperative biochemical recurrence (BCR)-free survival (Kaplan-Meier method). RESULTS: Intraprostatic incision rates were 2.3% pT2 PSMs, 6.0% BCIs and 5.4% BGTIs. There were slight variations in rate over time and with NSS technique. Benign incisions were located as follows: 46.8% right posterolateral, 37.5% left posterolateral, and 15.7% bilateral for BCIs; 58.6% bladder neck and 41.4% apical for BGTIs. The median (range) incision length, for solitary and multiple incisions respectively, was 4 (1-13) and 9 (2-25) mm for BCIs and 1 (1-5) and 2 (2-6) mm for BGTIs. BCI rate, but not BGTI rate, was significantly associated with NSS (P = 0.004) and PSM (P = 0.005), and increased PSM risk 3.6-fold. A PSM increased BCR risk two-fold (odds ratio 2.078, 95% confidence interval 1.383-3.122). BCR-free survival decreased significantly even for short PSMs (<1 mm; P < 0.001). CONCLUSIONS: Although the pT2 PSM rate was low (2.3%), the cumulative technical error rate (patients with at least one pT2 PSM, BCI or BGTI) was five-fold higher (12.5%). Categorising and mapping intraprostatic incisions is a tool surgeons can use in self-audits to identify areas of potential improvement, reduce errors, and improve surgical skills.


Assuntos
Erros Médicos , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Fatores Etários , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Fatores de Risco
18.
Prev Med ; 64: 48-53, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24726740

RESUMO

OBJECTIVE: The aim of this study is to assess whether patients at elevated risk of melanoma attended a dermatologist consultation after a General Practitioner referral and to determine individual predictors of non-compliance. METHOD: This survey included 1506 high-risk French patients (selected using the Self-Assessment Melanoma Risk Score) referred to a dermatologist between April and October 2011. Compliance was evaluated from January to April 2012, based on attendance at a dermatologist consultation (or scheduling an appointment). Demographic data and factors mapping the Health Belief Model were tested as correlates using a multivariate logistic regression. RESULTS: Compliance with referral was 58.4%. The top seven factors associated with non-compliance were as follows: GP advice to consult was unclear (OR=13.22; [7.66-23.56]); no previous participation in cancer screenings, including smear tests (OR=5.03; [2.23-11.83]) and prostate screening (OR=2.04; [1.06-3.97]); lack of knowledge that melanoma was a type of cancer (OR=1.94; [1.29-2.92]); and reporting no time to make an appointment (OR=2.08; [1.82-2.38]), forgetting to make an appointment (OR=1.26; [1.08-1.46]), long delays in accessing an appointment (OR=1.25; [1.12-1.41]), not being afraid of detecting something abnormal (OR=1.54; [1.35-1.78]), no need to consult a dermatologist to feel secure (OR=1.28; [1.09-1.51]). CONCLUSION: Physicians should be aware of the factors predicting patient compliance with referrals for dermatologist consultations; better General Practitioner counseling might enhance compliance in high-risk populations.


Assuntos
Dermatologia/estatística & dados numéricos , Detecção Precoce de Câncer/estatística & dados numéricos , Clínicos Gerais/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Melanoma/prevenção & controle , Cooperação do Paciente/estatística & dados numéricos , Relações Médico-Paciente , Adulto , Aconselhamento , Escolaridade , Feminino , França , Clínicos Gerais/normas , Humanos , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Ocupações , Cooperação do Paciente/psicologia , Projetos Piloto , Padrões de Prática Médica/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Medição de Risco , Fatores de Tempo
19.
Ann Fam Med ; 12(1): 21-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24445100

RESUMO

PURPOSE: Targeted interventions to reduce the risk and increase the early detection of melanoma have the potential to save lives. We aimed to assess the effect of such an intervention on patient prevention behavior. METHODS: We conducted a pilot clustered randomized controlled trial, comparing a targeted screening and education intervention with a conventional information-based campaign in 20 private surgeries in western France. In the intervention group, 10 general practitioners identified patients at elevated risk for melanoma with a validated assessment tool, the Self-Assessment Melanoma Risk Score (SAMScore), examined their skin, and counseled them using information leaflets. In the control group, 10 general practitioners displayed a poster and the leaflets in their waiting room and examined patients' skin at their own discretion. The main outcome measures were sunbathing and skin self-examinations among patients at elevated risk, assessed 5 months later with a questionnaire. RESULTS: Analyses were based on 173 patients. Compared with control patients, intervention patients were more likely to remember the campaign (81.4% vs 50.0%, P = .0001) and to correctly identify their elevated risk of melanoma (71.1% vs 42.1%, P = .001). Furthermore, intervention patients had higher levels of prevention behaviors: they were less likely to sunbathe in the summer (24.7% vs 40.8%, P = .048) and more likely to have performed skin self-examinations in the past year (52.6% vs 36.8%, P = .029). The intervention was not associated with any clear adverse effects, although there were trends whereby intervention patients were more likely to worry about melanoma and to consult their general practitioner again about the disease. CONCLUSIONS: The combination of use of the SAMScore and general practitioner examination and counseling during consultations is an efficient way to promote patient behaviors that may reduce melanoma risk. Extending the duration of follow-up and demonstrating an impact on morbidity and mortality remain major issues for further research.


Assuntos
Detecção Precoce de Câncer/métodos , Conhecimentos, Atitudes e Prática em Saúde , Melanoma/prevenção & controle , Educação de Pacientes como Assunto/métodos , Autoexame/estatística & dados numéricos , Neoplasias Cutâneas/prevenção & controle , Banho de Sol/estatística & dados numéricos , Adulto , Feminino , França , Humanos , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Projetos Piloto , Medição de Risco , Neoplasias Cutâneas/diagnóstico , Inquéritos e Questionários , Resultado do Tratamento
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