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1.
Acta Derm Venereol ; 102: adv00692, 2022 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-35312026

RESUMEN

Vitamin D status is influenced by well-known determinants, but factors associated with low 25-hydroxyvitamin D levels in the cutaneous melanoma population are not well defined. The aim of this study was to confirm the well-known determinants and to assess new determinants for 25-hydroxyvitamin D levels in a cutaneous melanoma population. In a prospectively included cohort of 387 patients with cutaneous melanoma the association of 25-hydroxyvitamin D levels with sex, age, body mass index, time of blood withdrawal, Fitzpatrick phototype, vitamin D supplementation, score for intensity of lifetime sun exposure, smoking, education level, hair and skin colour, eye colour, total number of benign naevi, freckles and parameters of chronic sun damage was investigated. In addition, 25-hydroxyvitamin D levels were correlated with pathological parameters of the primary tumour and melanoma stage (8th edition of the American Joint Committee on Cancer (AJCC). Univariate and multivariate logistic regressions were performed using R software. The following factors had a significant effect on vitamin D status: body mass index, seasonal time of blood sampling, vitamin D supplementation, and a subtype of skin, and hair colour.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Calcifediol , Humanos , Melanoma/patología , Neoplasias Cutáneas/patología , Vitamina D/análogos & derivados , Vitaminas , Melanoma Cutáneo Maligno
2.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34638912

RESUMEN

Cutaneous melanoma (CM) is the most aggressive form of skin cancer, and its worldwide incidence is rapidly increasing. Early stages can be successfully treated by surgery, but once metastasis has occurred, the prognosis is poor. However, some 5-10% of thick (≥2 mm) melanomas do not follow this scenario and run an unpredictable course. Little is known about the factors that contribute to metastasis in some patient with thick melanomas and the lack thereof in thick melanoma patients who never develop metastatic disease. We were therefore interested to study differential gene expression and pathway analysis and compare non-metastatic and metastatic thick melanomas. We found that the TNF-like weak inducer of apoptosis (TWEAK) pathway was upregulated in thick non-metastasizing melanomas. MAP3K14 (NIK1), BIRC2 (cIAP1), RIPK1, CASP7, CASP8, and TNF play an important role in inhibiting proliferation and invasion of tumor cells via the activation of the non-canonical NF-κB signaling pathway. In particular, this pathway sensitizes melanoma cells to TNF-alpha and activates the apoptosis module of the TWEAK pathway in thick non-metastasizing melanomas. Hence, our study suggests a potential role of the TWEAK pathway in inhibiting thick melanoma from metastasis. Exploitation of these genes and the pathway they control may open future therapeutic avenues.


Asunto(s)
Citocina TWEAK/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Melanoma/genética , Transducción de Señal/genética , Neoplasias Cutáneas/genética , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , RNA-Seq/métodos , Neoplasias Cutáneas/patología
3.
Acta Derm Venereol ; 99(12): 1154-1159, 2019 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-31314121

RESUMEN

The rising incidence of cutaneous melanoma and its stable high mortality rates despite innovative cancer care, require better prediction of the clinical outcome. In a large cutaneous melanoma population we explored whether the known clinical risk factors for melanoma susceptibility (nevus phenotype, phototype, family and personal history of melanoma and sun damage) affect melanoma outcomes. A total of 1,530 melanoma patients were included. Multivariable analysis adjusted for age, gender, melanoma stage, localization and subtype showed that familial melanoma, solar lentigines on head and neck, the back of hands, arms and shoulders were associated with a better relapse free survival. The presence of atypical naevi was associated with an increased risk of relapse. After Bonferroni correction, the correlation between presence of solar lentigines on the back of the hands and arms remained the most robust and significant prognostic factor for the relapse free survival in cutaneous melanoma patients.

4.
Mod Pathol ; 29(4): 347-58, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26867783

RESUMEN

Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. The role of T lymphocytes in tumor immunity has been extensively studied in melanoma, whereas less is known about the importance of B lymphocytes. The effects of plasma cells (PCs), in particular, are still obscure. The aim of this study was to characterize pathological features and clinical outcome of primary cutaneous melanomas associated with PCs. Moreover, we investigated the origins of the melanoma-associated PCs. Finally, we studied the outcome of patients with primary melanomas with PCs. We reviewed 710 melanomas to correlate the presence of PCs with histological prognostic markers. Immunohistochemistry for CD138 and heavy and light chains was performed in primary melanomas (PM) and in loco-regional lymph nodes (LN), both metastatic and not metastatic. In three PM and nine LN with frozen material, VDJ-rearrangement was analyzed by Gene Scan Analysis. Survival analysis was performed on a group of 85 primary melanomas >2 mm in thickness. Forty-one cases (3.7%) showed clusters/sheets of PCs. PC-rich melanomas occurred at an older age and were thicker, more often ulcerated and more mitotically active (P<0.05). PCs were polyclonal and often expressed IgA in addition to IgG. In LN, clusters/sheets of IgA+ PCs were found both in the sinuses and subcapsular areas. Analysis of VDJ-rearrangements showed the IgA to be oligoclonal. Melanomas with clusters/sheets of PCs had a significantly worse survival compared with melanomas without PCs while, interestingly, melanomas with sparse PCs were associated with a better clinical outcome (P=0.002). In conclusion, melanomas with sheets/clusters of PCs are associated with worse prognosis. IgG and IgA are the isotypes predominantly produced by these PCs. IgA oligoclonality suggests an antigen-driven response that facilitates melanoma progression by a hitherto unknown mechanism.


Asunto(s)
Linfocitos Infiltrantes de Tumor/inmunología , Melanoma/inmunología , Células Plasmáticas/inmunología , Neoplasias Cutáneas/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Inmunoglobulina A , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Pronóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Adulto Joven
5.
Mod Pathol ; 27(8): 1088-100, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24390218

RESUMEN

In many human cancers, the epithelial-to-mesenchymal transition has an important role in the induction of cancer stem-like cells, and hence, in the causation of intratumoral heterogeneity. This process, also referred to as mesenchymal mimicry, is, however, only poorly understood in melanoma and histological correlation is still lacking. In an immunohistochemical analysis of a large prospective series of 220 primary and metastatic melanomas for the well-known epithelial-to-mesenchymal transition marker FN1, we observed melanoma cells with high FN1 expression in metastases with ischemic necrosis, but rarely or not at all in samples lacking evidence of hypoxia. In a blinded, retrospective series of 82 melanoma metastases with 10-year follow-up, the presence of clusters of these FN1(high) melanoma cells correlated significantly with shortened melanoma-specific survival, highlighting the prognostic value of their presence. We describe in detail the unique light- and electron-microscopic features of these FN1(high) melanoma cells, enabling their identification in routinely hematoxylin-and-eosin-stained sections. In addition, by laser microdissection and subsequent gene expression analysis and immunohistochemistry, we highlight their distinctive, molecular phenotype that includes expression of various markers of the epithelial-to-mesenchymal transition (eg, ZEB1) and of melanoma stem-like cells (eg, NGFR), and lack of immunoreactivity for the melanocytic marker MITF. This phenotype could be reproduced in vitro by culturing melanoma cells under hypoxic conditions. Functionally, the hypoxic microenvironment was shown to induce a more migratory and invasive cell type. In conclusion, we identified a novel clinically relevant FN1(high)MITF(low) cell type in melanoma associated with ischemic necrosis, and propose that these cells reside at the crossroad of the epithelial-to-mesenchymal transition and stem-like cell induction, plausibly triggered by the hypoxic environment.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Fibronectinas/metabolismo , Melanoma/metabolismo , Factor de Transcripción Asociado a Microftalmía/metabolismo , Células Madre Neoplásicas/metabolismo , Neoplasias Cutáneas/metabolismo , Microambiente Tumoral , Biomarcadores de Tumor/genética , Hipoxia de la Célula , Línea Celular Tumoral , Movimiento Celular , Transición Epitelial-Mesenquimal , Fibronectinas/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Captura por Microdisección con Láser , Melanoma/genética , Melanoma/mortalidad , Melanoma/secundario , Melanoma/ultraestructura , Factor de Transcripción Asociado a Microftalmía/genética , Microscopía Electrónica de Transmisión , Necrosis , Invasividad Neoplásica , Células Madre Neoplásicas/patología , Fenotipo , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Estudios Retrospectivos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/ultraestructura , Factores de Tiempo
6.
Melanoma Res ; 34(2): 125-133, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38348498

RESUMEN

Decrease of vitamin D receptor (VDR) expression is observed in melanocytic naevi and melanoma compared to normal skin. Little is known about factors influencing VDR expression in cutaneous melanoma (CM). We investigated the correlation of VDR expression in CM with 25-hydroxy vitamin D (25OHD) levels, demographic/clinical parameters, genetic variants of VDR and pathology of the primary tumor. Demographic/clinical parameters were recorded in 407 prospectively recruited CM patients of a multi-center controlled study (ViDMe trial). We determined VDR expression both in the nucleus and in the cytoplasm by semi-quantitative assessment in CM tissue using histochemistry in 279 patients, expressed in percentages and histoscore (H-score). Genomic DNA from 332 patients was extracted to genotype thirteen VDR single nucleotide polymorphisms (SNPs) using TaqMan. VDR expression in CM tissue from 279 patients was correlated with clinical/demographic parameters and 25OHD levels (univariable and multivariable analysis), VDR SNPs (univariable analysis) and pathology parameters of primary CM tissue (univariable analysis). Cytoplasmic VDR expression was increased in patients who stated to have a high sun exposure during their life compared to patients with low sun exposure (p H-score,univariable : 0.001, p H-score,multivariable : 0.004). The A allele of the genetic VDR polymorphism Fok1 was associated with a higher expression of the VDR in the cytoplasm (p cytoplasmic, univariable : 0.001 and p H-score, univariable : 0.02). In the primary tumor, presence of mitosis (p nucleus,%, univariable : 0.002) and perineural invasion (p nucleus,%,univariable : 0.03) were significantly associated with low nuclear VDR expression. ClinicalTrials.gov Identifier: NCT01748448.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Alelos , Melanoma/genética , Receptores de Calcitriol/genética , Piel , Neoplasias Cutáneas/genética
7.
Thorax ; 68(1): 111-3, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22863757

RESUMEN

We present a case of a 32-year-old woman who was diagnosed with lymphangioleiomyomatosis (LAM) after detecting a mass in the upper anterior mediastinum. Two years after presentation another metastatic localisation of LAM occurred in the cervical region. With this article we would like to highlight the fact that there are still a lot of unanswered questions, especially regarding the best management of extrapulmonary LAM.


Asunto(s)
Linfangioleiomiomatosis/diagnóstico , Recurrencia Local de Neoplasia/parasitología , Neoplasias del Timo/diagnóstico , Adulto , Biopsia con Aguja , Broncoscopía/métodos , Progresión de la Enfermedad , Disnea/diagnóstico , Disnea/etiología , Femenino , Estudios de Seguimiento , Hemoptisis/diagnóstico , Hemoptisis/etiología , Humanos , Inmunohistoquímica , Linfangioleiomiomatosis/cirugía , Imagen por Resonancia Magnética/métodos , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Enfermedades Raras , Neoplasias del Timo/cirugía , Tomografía Computarizada por Rayos X/métodos
8.
Eur J Cancer ; 190: 112949, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37453241

RESUMEN

OBJECTIVE: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. MATERIALS AND METHODS: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. RESULTS: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). CONCLUSION: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.


Asunto(s)
Sarcoma de Kaposi , Sarcoma , Neoplasias de los Tejidos Blandos , Adulto , Humanos , Estudios Retrospectivos , Quimioterapia del Cáncer por Perfusión Regional/métodos , Sarcoma/patología , Melfalán/uso terapéutico , Extremidades/patología , Neoplasias de los Tejidos Blandos/patología , Perfusión , Factor de Necrosis Tumoral alfa , Antineoplásicos Alquilantes/uso terapéutico
9.
Onkologie ; 35(1-2): 14-7, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22310339

RESUMEN

BACKGROUND: Patients with progressive mesenchymal tumours after standard chemotherapy have poor outcome. Trabectedin is approved in Europe as 24-h intravenous (i.v.) infusion q3w in this setting. We report the use of disposable elastomeric pumps for ambulatory treatment with trabectedin. MATERIAL AND METHODS: Pre-treated sarcoma patients were offered trabectedin 1.5 mg/m(2) as 24-h i.v. infusion via port catheter, either as inpatients using electronic pumps or as outpatients using the Baxter LV10 pump. Co-medication consisted of antiemetics including dexamethasone. RESULTS: 21/28 patients with distant metastasis and/or local relapse elected outpatient therapy and received 130 cycles (median 3, range 1-24). Dose reductions were done in 60 cycles, mainly due to laboratory adverse events (AEs). Best response (Response Evaluation Criteria in Solid Tumours (RECIST)) was 4 cases of confirmed partial remission (PR), 6 cases of stable disease (SD), and 11 cases of progressive disease (PD). Grade 3/4 (Common Toxicity Criteria (CTC)) AEs were limited to 1 case each of haemorrhage and lung embolism; other AEs were in line with published trabectedin experience. 1 port catheter contamination required replacement, 1 catheter thrombosis occurred and 1 extravasation due to needle dislocation was observed. CONCLUSIONS: Outpatient administration of trabectedin as 24-h infusion using Baxter LV10 pumps is preferred by the vast majority of patients; it is feasible, safe, effective, cost efficient, and should be considered as routine practice in this clinical setting.


Asunto(s)
Atención Ambulatoria/métodos , Dioxoles/administración & dosificación , Bombas de Infusión Implantables , Cuidados Paliativos/métodos , Sarcoma/tratamiento farmacológico , Sarcoma/patología , Tetrahidroisoquinolinas/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas/instrumentación , Infusiones Intravenosas/métodos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Trabectedina , Resultado del Tratamiento
10.
Support Care Cancer ; 19(7): 883-98, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21556721

RESUMEN

PURPOSE: Malfunction of totally implantable venous access devices is a common complication. The purpose was to identify definitions used to describe malfunction and to investigate the incidence of malfunction in different types of port and catheter designs. METHODS: Relevant studies were identified in PubMed that were published between January 1993 and February 2011. Empirical studies reporting functional outcomes in adults and where, at least 95% of the studied population consisted of onco-hematology patients with a newly inserted chest or arm port, were selected. The following data were extracted: patient and totally implantable venous access devices (TIVAD) characteristics, study design, definitions of malfunction, and functional outcomes. Two independent reviewers assessed the methodological quality of the series. RESULTS: Of the 4,886 potentially relevant articles, 57 were selected, involving 14,311 TIVADs. Twenty-nine percent of the studies explicitly defined malfunction. Malfunction incidence rates were expressed in six different ways, including the proportion of affected devices per inserted devices (incidence 0-47%); the number of affected devices per 1,000 catheter days (incidence 0-2.24 per 1,000 catheter days); and the number of malfunctions over the total number of accessing attempts (incidence 0-26%). CONCLUSIONS: Heterogeneity in the definitions used to describe device malfunction was evident. A broad range in the reported incidence of malfunction and in the kind of calculation and reporting methods was also found. Methodological quality of the studies was often poor. Standardization of definitions and accurate outcome measurement is needed. Calculation and report of malfunction incidence should be based on prospective data collected at the moment of an accession attempt.


Asunto(s)
Catéteres de Permanencia/efectos adversos , Neoplasias/complicaciones , Cateterismo Venoso Central/efectos adversos , Falla de Equipo , Hematología , Humanos , Incidencia , Oncología Médica , Factores de Riesgo
11.
J Vasc Access ; 22(5): 716-725, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32613887

RESUMEN

BACKGROUND: Subcutaneously anchored securement devices (or subcutaneous engineered securement devices) have been introduced recently into the clinical practice, but the number of published studies is still scarce. The Italian Group of Long-Term Central Venous Access Devices (GAVeCeLT)-in collaboration with WoCoVA (World Congress on Vascular Access)-has developed a Consensus about the effectiveness, safety, and cost-effectiveness of such devices. METHODS: After the definition of a panel of experts, a systematic collection and review of the literature on subcutaneously anchored securement devices was performed. The panel has been divided in two working groups, one focusing on adult patients and the other on children and neonates. RESULTS: Although the quality of evidence is generally poor, since it is based mainly on non-controlled prospective studies, the panel has concluded that subcutaneously anchored securement devices are overall effective in reducing the risk of dislodgment and they appear to be safe in all categories of patients, being associated only with rare and negligible local adverse effects; cost-effectiveness is demonstrated-or highly likely-in specific populations of patients with long-term venous access and/or at high risk of dislodgment. CONCLUSION: Subcutaneously anchored securement is a very promising strategy for avoiding dislodgment. Further studies are warranted, in particular for the purpose of defining (a) the best management of the anchoring device so to avoid local problems, (b) the patient populations in which it may be considered highly cost-effective and even mandatory, (c) the possible benefit in terms of reduction of other catheter-related complications such as venous thrombosis and/or infection, and-last but not least-(d) their impact on the workload and stress level of nurses taking care of the devices.


Asunto(s)
Cateterismo Venoso Central , Cateterismo Periférico , Catéteres Venosos Centrales , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Niño , Consenso , Humanos , Recién Nacido , Estudios Prospectivos
12.
Elife ; 92020 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-32057296

RESUMEN

In melanoma, the lymphocytic infiltrate is a prognostic parameter classified morphologically into 'brisk', 'non-brisk' and 'absent' entailing a functional association that has never been proved. Recently, it has been shown that lymphocytic populations can be very heterogeneous, and that anti-PD-1 immunotherapy supports activated T cells. Here, we characterize the immune landscape in primary melanoma by high-dimensional single-cell multiplex analysis in tissue sections (MILAN technique) followed by image analysis, RT-PCR and shotgun proteomics. We observed that the brisk and non-brisk patterns are heterogeneous functional categories that can be further sub-classified into active, transitional or exhausted. The classification of primary melanomas based on the functional paradigm also shows correlation with spontaneous regression, and an improved prognostic value when compared to that of the brisk classification. Finally, the main inflammatory cell subpopulations that are present in the microenvironment associated with activation and exhaustion and their spatial relationships are described using neighbourhood analysis.


Asunto(s)
Linfocitos Infiltrantes de Tumor/inmunología , Melanoma/patología , Análisis de la Célula Individual/métodos , Neoplasias Cutáneas/patología , Humanos , Melanoma/inmunología , Neoplasias Cutáneas/inmunología , Microambiente Tumoral
13.
J Thromb Thrombolysis ; 28(4): 477-81, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19225865

RESUMEN

BACKGROUND: Microplasmin, a truncated form of plasmin, degrades fibrin and reacts with the circulating inhibitor alpha(2)-antiplasmin. We investigated the safety and efficacy of intra-catheter microplasmin bolus administration for the restoration of catheter function in long-term venous access catheter thrombosis. METHODS: This open-label, ascending-dose, pilot study enrolled 31 subjects. Two doses of microplasmin were evaluated, (5 mg and 8 mg) administered via a 2 ml intra-catheter bolus injection in 10 and 21 patients respectively. Catheter function was evaluated 30 min after the first bolus administration. In case of incomplete catheter function restoration, a second bolus was administered with reassessment of catheter function 30 min thereafter. RESULTS: After the first bolus, complete restoration of catheter withdrawal function was observed in 5 out of 10 (50%) and 14 of out 21 (66%) subjects treated with 5 mg and 8 mg respectively and in 8 out of 10 (80%) and 18 out of 21 (86%) subjects after a second administration of microplasmin. No bleeding complications nor other adverse events were related to microplasmin. CONCLUSIONS: In this pilot trial, microplasmin restored catheter function in a safe and effective way.


Asunto(s)
Cateterismo Venoso Central/efectos adversos , Fibrinolisina/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Trombosis de la Vena/tratamiento farmacológico , Trombosis de la Vena/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Catéteres de Permanencia/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Factores de Tiempo , Adulto Joven
14.
Melanoma Res ; 29(6): 590-595, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-30681428

RESUMEN

The rising incidence of cutaneous melanoma (CM), an aggressive skin cancer, emphasizes the need for novel biomarkers to guide personalized care and better predict outcome. Genetic factors including germline risk variants are promising candidates for this aim. We explored the association between germline risk variants and melanoma outcome in a large genetically homogenous Belgian melanoma population, focusing on single nucleotide polymorphisms which generated the highest association with melanoma susceptibility. Between 2004 and 2014, blood samples of 1088 patients with histologically confirmed CM were collected and genotyped for nine variants. Cox proportional hazard models were used to assess the association between each single nucleotide polymorphism and relapse-free survival and overall survival, adjusted by age, sex, melanoma stage, site, and subtype. We identified significant associations for rs869330 (in the methylthioadenosine phosphorylase - MTAP gene) with overall survival (hazard ratio = 0.760, P = 0.048, 95% confidence interval: 0.580-0.998) and relapse-free survival (hazard ratio = 0.800, P = 0.020, 95% confidence interval: 0.650-0.970). This exploratory study is the first to show a significant association between the rs869330 variant (in the MTAP gene) and outcome in a large CM population.


Asunto(s)
Melanoma/genética , Purina-Nucleósido Fosforilasa/genética , Neoplasias Cutáneas/genética , Bélgica/epidemiología , Susceptibilidad a Enfermedades , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Genotipo , Humanos , Masculino , Melanoma/enzimología , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Modelos de Riesgos Proporcionales , Neoplasias Cutáneas/enzimología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Análisis de Supervivencia
15.
Mol Cancer Ther ; 18(6): 1168-1178, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30962320

RESUMEN

Soft-tissue sarcomas (STS) represent a heterogeneous group of rare, malignant tumors of mesenchymal origin. Reliable in vivo sarcoma research models are scarce. We aimed to establish and characterize histologically and molecularly stable patient-derived xenograft (PDX) models from a broad variety of STS subtypes. A total of 188 fresh tumor samples from consenting patients with localized or advanced STS were transplanted subcutaneously in NMRI-nu/nu-immunodeficient mice. Once tumor growth was observed, the material was passaged to a next generation of mice. A patient-derived tumor sample was considered "successfully engrafted" whenever the sample was transplanted to passage 1. A PDX model was considered "established" when observing stable morphologic and molecular features for at least two passages. With every passage, histologic and molecular analyses were performed. Specific genomic alterations and copy-number profile were assessed by FISH and low coverage whole-genome sequencing. The tumor engraftment rate was 32% (61/188) and 188 patient samples generated a total of 32 PDX models, including seven models of myxofibrosarcoma, five dedifferentiated liposarcoma, five leiomyosarcoma, three undifferentiated pleomorphic sarcoma, two malignant peripheral nerve sheet tumor models, and single models of synovial sarcoma and some other (ultra)rare subtypes. Seventeen additional models are in early stages of engraftment (passage 1-2). Histopathologic and molecular features were compared with the original donor tumor and were stable throughout passaging. The platform is used for studies on sarcoma biology and suited for in vivo preclinical drug testing as illustrated by a number of completed and ongoing laboratory studies.


Asunto(s)
Modelos Animales de Enfermedad , Xenoinjertos/patología , Sarcoma/patología , Sarcoma/cirugía , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biopsia , Femenino , Genotipo , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Pacientes , Fenotipo , Secuenciación Completa del Genoma , Adulto Joven
17.
Prosthet Orthot Int ; 42(3): 254-257, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28726572

RESUMEN

BACKGROUND: Epidermolysis bullosa dystrophica is a rare dermatological disease characterized by extreme skin fragility and elevated risk of developing a squamous cell carcinoma. In some cases, amputation of a limb is necessary. Case description and methods: A 37-year-old man with recessive, severe generalized epidermolysis bullosa dystrophica developed a squamous cell carcinoma on the right forearm requiring a below-elbow amputation. Preoperative advice concerning indication and level of amputation was given. Due to potential skin problems, a conventional prosthesis was not feasible. Findings and outcomes: A custom-designed adaptive prosthesis with an upper arm cuff was trialed and was well tolerated. Multiple working tools, attached with a rotation and inclination system, allowed independence and return to work. CONCLUSION: Despite multiple potential skin problems of the stump, the patient was successfully fitted with a custom-designed adaptive prosthesis. Preparation for this fitting was done by a comprehensive multidisciplinary patient-centered approach. Clinical relevance Despite severe skin fragility, a patient with epidermolysis bullosa dystrophica was successfully fitted with a custom-designed adaptive upper limb prosthesis allowing good functional outcome. This required a multidisciplinary and patient-centered approach.


Asunto(s)
Muñones de Amputación/patología , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/cirugía , Epidermólisis Ampollosa Distrófica/complicaciones , Neoplasias Cutáneas/cirugía , Adulto , Amputación Quirúrgica/métodos , Amputación Quirúrgica/rehabilitación , Carcinoma de Células Escamosas/patología , Epidermólisis Ampollosa Distrófica/patología , Epidermólisis Ampollosa Distrófica/fisiopatología , Estudios de Seguimiento , Antebrazo , Humanos , Masculino , Diseño de Prótesis , Ajuste de Prótesis/métodos , Medición de Riesgo , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Resultado del Tratamiento
18.
BMJ Open ; 8(2): e016058, 2018 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-29478011

RESUMEN

OBJECTIVES: To assess the effect on needed nursing time for dressing change. DESIGN, SETTING, PARTICIPANTS: A parallel-group, open-label, randomised controlled trial in patients who are in need for a peripherally inserted central catheter insertion in one teaching hospital in Belgium. The follow-up lasted 180 days or until catheter removal, whatever came first. A computer generated table was used to allocate devices. Randomised patients were 105 adults (StatLock, n=53; SecurAcath, n=52) and primary analysis was based on all patients (n=92) with time measurements (StatLock, n=43; SecurAcath, n=49). INTERVENTIONS: StatLock which has to be changed weekly versus SecurAcath which could remain in place for the complete catheter dwell time. MAIN OUTCOME MEASURE: Needed time for the dressing change at each dressing change (SecurAcath) or at each dressing change combined with the change of the securement device (StatLock). RESULTS: Median time needed for dressing change was 7.3 min (95% CI 6.4 min to 8.3 min) in the StatLock group and in the SecurAcath group 4.3 min (95% CI 3.8 min to 4.9 min) (P<0.0001). The time in the SecurAcath group was reduced with 41% (95% CI 29% to 51%). Incidence rates of migration, dislodgement and catheter-related bloodstream infection were comparable across groups. Pain scores were higher with SecurAcath than with StatLock at insertion (P=0.02) and at removal (P<0.001) and comparable during dressing change (P=0.38) and during dwell time (P=0.995). User-friendliness was scored at insertion and removal. All statements regarding the user-friendliness were scored significantly higher for StatLock than for SecurAcath (P<0.05). Only for the statement regarding the recommending routine use of the device, which was asked at removal, no difference was found between the two devices (P=0.32). CONCLUSION: Use of SecurAcath saves time during dressing change compared with StatLock. Training on correct placement and removal of SecurAcath is critical to minimise pain. TRIAL REGISTRATION NUMBER: NCT02311127; Pre-results.


Asunto(s)
Vendajes , Infecciones Relacionadas con Catéteres/epidemiología , Cateterismo Periférico/métodos , Remoción de Dispositivos/instrumentación , Anciano , Bélgica , Cateterismo Periférico/efectos adversos , Femenino , Hospitales de Enseñanza , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Tiempo
19.
Melanoma Res ; 27(5): 507-510, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28800030

RESUMEN

Concurrent BRAF-MEK inhibition improves clinical outcomes in patients with advanced BRAF V600E/K-mutant melanoma. There is currently less evidence for the efficacy of this treatment in patients with rare BRAF non-V600E/K genotypes. We report on two patients with rare BRAF exon 15 mutations - BRAF A598_T599insV and V600_K601delinsE - obtaining clinical benefit and a radiological response to inhibitors directed against the mitogen-activated protein kinase pathway. This highlights the importance of using tests that detect both V600E/K and non-V600E/K BRAF mutations to keep open the possibility of treatment with targeted therapy in patients with uncommon, yet potentially actionable, BRAF exon 15 mutations.


Asunto(s)
Exones , Melanoma/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Supervivencia sin Enfermedad , Humanos , Masculino , Melanoma/enzimología , Melanoma/patología , Neoplasias Cutáneas/enzimología , Neoplasias Cutáneas/patología
20.
J Vasc Access ; 18(2): 89-96, 2017 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-28127726

RESUMEN

A short peripheral intravenous catheter or cannula (PIVC) is frequently used to deliver chemotherapy in oncology practice. Although safe and easy to insert, PIVCs do fail, leading to personal discomfort for patients and adding substantially to treatment costs. As the procedure of peripheral catheterization is invasive, there is a need for greater consistency in the choice, insertion and management of short PIVCs, particularly in the oncology setting where there is a growing trend for patients to receive many different courses of IV treatment over a number of years, sometimes with only short remissions. This article reviews best practice with respect to PIVCs in cancer patients and considers the necessity for bundling these actions. Two care bundles, addressing both insertion and ongoing care and maintenance, are proposed. These have the potential to improve outcomes with the use of short PIVCs for vascular access in oncology practice.


Asunto(s)
Antineoplásicos/efectos adversos , Cateterismo Venoso Central/métodos , Cateterismo Periférico/métodos , Oncología Médica/métodos , Neoplasias/tratamiento farmacológico , Paquetes de Atención al Paciente , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/instrumentación , Cateterismo Venoso Central/normas , Cateterismo Periférico/efectos adversos , Cateterismo Periférico/instrumentación , Cateterismo Periférico/normas , Catéteres de Permanencia , Catéteres Venosos Centrales , Diseño de Equipo , Humanos , Oncología Médica/normas , Mejoramiento de la Calidad , Indicadores de Calidad de la Atención de Salud , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
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