Publications by authors named "Francisco Cuellar"

20 Publications

  • Page 1 of 1

Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families.

BMC Public Health 2021 04 23;21(1):692. Epub 2021 Apr 23.

Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands.

Background: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited.

Methods: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates.

Results: A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis.

Conclusions: Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-021-10424-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063451PMC
April 2021

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT.

J Am Acad Dermatol 2019 Aug 5;81(2):386-394. Epub 2019 Feb 5.

Department of Clinical Sciences, Lund University Hospital Lund, Sweden; Department of Surgery, Lund University Hospital, Lund, Sweden.

Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved.

Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics.

Results: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance.

Conclusion: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2019.01.079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634996PMC
August 2019

Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families.

J Invest Dermatol 2017 12 19;137(12):2606-2612. Epub 2017 Aug 19.

Melanoma Institute Australia, Westmead, New South Wales, Australia; Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, New South Wales, Australia.

Germline mutations in CDKN2A are frequently identified among melanoma kindreds and are associated with increased atypical nevus counts. However, a clear relationship between pathogenic CDKN2A mutation carriage and other nevus phenotypes including counts of common acquired nevi has not yet been established. Using data from GenoMEL, we investigated the relationships between CDKN2A mutation carriage and 2-mm, 5-mm, and atypical nevus counts among blood-related members of melanoma families. Compared with individuals without a pathogenic mutation, those who carried one had an overall higher prevalence of atypical (odds ratio = 1.64; 95% confidence interval = 1.18-2.28) nevi but not 2-mm nevi (odds ratio = 1.06; 95% confidence interval = 0.92-1.21) or 5-mm nevi (odds ratio = 1.26; 95% confidence interval = 0.94-1.70). Stratification by case status showed more pronounced positive associations among non-case family members, who were nearly three times (odds ratio = 2.91; 95% confidence interval = 1.75-4.82) as likely to exhibit nevus counts at or above the median in all three nevus categories simultaneously when harboring a pathogenic mutation (vs. not harboring one). Our results support the hypothesis that unidentified nevogenic genes are co-inherited with CDKN2A and may influence carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2017.07.829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701856PMC
December 2017

Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma.

Genet Med 2016 07 17;18(7):727-36. Epub 2015 Dec 17.

Unidad de Lesiones Pigmentadas, Cátedra de Dermatología, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay.

Purpose: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America.

Methods: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained.

Results: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients.

Conclusion: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/gim.2015.160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940430PMC
July 2016

Skin examination behavior: the role of melanoma history, skin type, psychosocial factors, and region of residence in determining clinical and self-conducted skin examination.

Arch Dermatol 2012 Oct;148(10):1142-51

School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales, Kensington, NSW, Australia.

Objective: To examine the frequency and correlates of skin examination behaviors in an international sample of individuals at varying risk of developing melanoma.

Design: A cross-sectional, web-based survey.

Setting: Data were collected from the general population over a 20-month period on behalf of the Melanoma Genetics Consortium (GenoMEL).

Participants: A total of 8178 adults from Northern (32%), Central (33%), and Southern (14%) Europe, Australia (13%), and the United States (8%).

Main Outcome Measures: Self-reported frequency of skin self-examination (SSE) and clinical skin examination (CSE).

Results: After adjustment for age and sex, frequency of skin examination was higher in both Australia (odds ratio [OR]SSE=1.80 [99% CI, 1.49-2.18]; ORCSE=2.68 [99% CI, 2.23-3.23]) and the United States (ORSSE=2.28 [99% CI, 1.76-2.94]; ORCSE=3.39 [99% CI, 2.60-4.18]) than in the 3 European regions combined. Within Europe, participants from Southern Europe reported higher rates of SSE than those in Northern Europe (ORSSE=1.61 [99% CI, 1.31-1.97]), and frequency of CSE was higher in both Central (ORCSE=1.47 [99% CI, 1.22-1.78]) and Southern Europe (ORCSE=3.46 [99% CI, 2.78, 4.31]) than in Northern Europe. Skin examination behavior also varied according to melanoma history: participants with no history of melanoma reported the lowest levels of skin examination, while participants with a previous melanoma diagnosis reported the highest levels. After adjustment for region, and taking into account the role of age, sex, skin type, and mole count, engagement in SSE and CSE was associated with a range of psychosocial factors, including perceived risk of developing melanoma; perceived benefits of, and barriers to, skin examination; perceived confidence in one's ability to engage in screening; and social norms. In addition, among those with no history of melanoma, higher cancer-related worry was associated with greater frequency of SSE.

Conclusions: Given the strong association between psychosocial factors and skin examination behaviors, particularly among people with no history of melanoma, we recommend that greater attempts be made to integrate psycho-education into the fabric of public health initiatives and clinical care, with clinicians, researchers, and advocacy groups playing a key role in guiding individuals to appropriate tools and resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/archdermatol.2012.1817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965805PMC
October 2012

Predictors of sun protection behaviors and severe sunburn in an international online study.

Cancer Epidemiol Biomarkers Prev 2010 Sep 19;19(9):2199-210. Epub 2010 Jul 19.

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Background: The incidence of melanoma continues to increase in many countries, and primary prevention of melanoma includes avoidance of sunburn as well as adequate sun protection behavior. The aim of this study was to examine the prevalence of self-reported sun protection behaviors and sunburn in users of the Internet, and to identify the demographic, clinical, and attitudinal/motivational correlates of sun protection behaviors.

Methods: Self-report data were gathered on behalf of the GenoMEL consortium using an online survey available in 10 different languages, and 8,178 individuals successfully completed at least 80% of survey items, with 73% of respondents from Europe, 12% from Australia, 7% from the United States, 2% from Israel, and 6% from other countries.

Results: Half of all respondents and 27% of those with a previous melanoma reported at least one severe sunburn during the previous 12 months. The strongest factors associated with sun protection behavior were perceived barriers to protection (beta = -0.44/beta = -0.37), and respondents who reported a positive attitude toward suntans were less likely to protect (beta = -0.16/beta = -0.14). Reported use of protective clothing and shade, as well as avoidance of midday sun exposure, were more strongly related to reduced risk of sunburn than sunscreen use.

Conclusions: Despite widespread dissemination of public health messages about the importance of sun protection, a substantial proportion of this international sample, including respondents with a previous melanoma, reported inadequate sun protection behaviors resulting in severe sunburn.

Impact: Future strategies to decrease sunburn should target the practical, social, and psychological barriers associated with nonuptake of sun protection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-10-0196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672402PMC
September 2010

Melanoma risk factors, perceived threat and intentional tanning: an international online survey.

Eur J Cancer Prev 2010 May;19(3):216-26

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Cutaneous melanoma continues to increase in incidence in many countries, and intentional tanning is a risk factor for melanoma. The aim of this study was to understand how melanoma risk factors, perceived threat and preferences for a suntan relate to intentional tanning. Self-report data were collected on behalf of GenoMEL (www.genomel.org) from the general population using an online survey. A total of 8178 individuals completed the survey, with 72.8% of respondents being from Europe, 12.1% from Australia, 7.1% from the US, 2.5% from Israel and 5.5% from other countries. Seven percent of respondents had previously been diagnosed with melanoma and 8% had at least one first-degree relative with a previous melanoma. Overall, 70% reported some degree of intentional tanning during the past year, and 38% of respondents previously diagnosed with melanoma had intentionally tanned. The total number of risk factors was positively correlated with perceived risk of melanoma [correlation coefficient (rho) = 0.27], and negatively correlated with intentional tanning (rho = -0.16). Preference for a dark suntan was the strongest predictor of intentional tanning [regression coefficient (beta) = 0.35, P<0.001], even in those with a previous melanoma (beta = 0.33, P<0.01). A substantial proportion of participants reported having phenotypic and behavioural risk factors for melanoma. The preference regarding suntans seemed more important in the participants' decision to intentionally tan than their perceived risk of developing melanoma, and this finding was consistent among respondents from different countries. The drive to sunbathe to tan is a key factor to be moderated if melanoma incidence is to be reduced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CEJ.0b013e3283354847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672405PMC
May 2010

Studying regression of seborrheic keratosis in lichenoid keratosis with sequential dermoscopy imaging.

Dermatology 2010 9;220(2):103-9. Epub 2009 Dec 9.

Department of Dermatology, Hospital de Sant Pau i Santa Tecla, Tarragona, Spain.

Background: Lichenoid keratosis (LK) is a well-described entity that has been proposed to represent a regressive response to a pre-existent epidermal lesion.

Aims: To evaluate the natural evolution of a series of cases showing the intermediate stage of the regression of seborrheic keratosis in LK using sequential dermoscopy imaging over time.

Material And Methods: A series of lesions with dermoscopic areas of seborrheic keratosis and LK in the same tumor were consecutively collected for over 3 years at the Dermatology Department of the Hospital de Sant Pau i Santa Tecla, Tarragona, Spain. Sequential dermoscopic images of each case were collected quarterly for 1 year. At the end of the follow-up, all the lesions were biopsied.

Results: A total of 22 cases were collected. At the end of the follow-up, the LK part increased in all the lesions. In 11 cases (50%), the seborrheic keratosis part disappeared completely, and in another 5 cases (22.7%), seborrheic keratosis comprised only 10% of the remaining area.

Conclusions: These dermoscopic study findings support the proposal that LK represents a regressive response to a pre-existent epidermal lesion, in this case seborrheic keratosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000265556DOI Listing
June 2010

Pyogenic granuloma clinically and dermoscopically mimicking pigmented melanoma.

Dermatol Online J 2009 Oct 15;15(10):10. Epub 2009 Oct 15.

Dermatology Department, Hospital de Sant Pau i Santa Tecla, Tarragona, Spain.

Pyogenic granuloma is a common, benign, acquired, vascular growth of skin and mucous membranes that usually presents as a solitary, rapidly, growing, papule or polyp that bleeds easily after minor trauma. The clinical diagnosis of this lesion is usually straightforward. Moreover, the dermoscopic features associated with pyogenic granulomas have been described recently. However, occasionally this tumor can be difficult to differentiate clinically and dermoscopically from other pigmented and vascular lesions. We report the case of an 18-year-old male who presented with a round, purple-black nodule with hemorrhagic crust, 1 cm in diameter, located on the lower part of the thorax. Dermoscopic evaluation revealed the presence of a blue-white veil, a black blotch, polymorphous atypical vessels, milky-red areas, and hemorrhagic crusts. The subsequent histopathological examination revealed a pyogenic granuloma. We present a case of pyogenic granuloma clinically and dermoscopically indistinguishable from a pigmented malignant melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2009

New dermoscopic pattern in actinic keratosis and related conditions.

Arch Dermatol 2009 Jun;145(6):732

Unidad de Dermatología Quirúrgica, Hospital Clinic, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/archdermatol.2009.86DOI Listing
June 2009

Dermoscopy of early recurrent basal cell carcinoma.

Arch Dermatol 2008 Sep;144(9):1254

Unidad de Dermatología Quirúrgica, Hospital Clinic, Institut de Investigacions Biomediques Cientifiques Agusti Pi I Suryer, Barcelona, Spain.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/archderm.144.9.1254DOI Listing
September 2008

Cutaneous phenotype and MC1R variants as modifying factors for the development of melanoma in CDKN2A G101W mutation carriers from 4 countries.

Int J Cancer 2007 Aug;121(4):825-31

Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA.

The G101W founder mutation is the most common CDKN2A mutation in Italy, Spain, and France. As the background of modifying genes, environmental exposures, and sun behavior vary across countries, studying G101W carriers from distinct countries offers a unique opportunity to evaluate possible modifying factors in melanoma development. We evaluated 76 G101W cases and 59 carrier controls from France, Italy, Spain, and the United States. Hair color and dysplastic nevi distributions differed significantly in cases and controls across the 4 study groups. Cases also varied significantly for eye color, freckling, and nevi. The distribution of MC1R variants in cases differed significantly across study groups because 12% of Italian melanoma patients had > or =2 MC1R variants vs. >50% for the other case groups. Several MC1R covariates showed significant associations with melanoma risk in all groups combined and in the American, French, and Spanish samples; no significant findings were observed in the Italian sample. In multiple-case families, the number and type of MC1R variants varied significantly between multiple-primary-melanoma and single-primary-melanoma patients from the 4 groups; there was also a significant decrease in median age at melanoma diagnosis as the number or type of MC1R variants increased. The variation in the effects of the cutaneous phenotypic and MC1R factors across the study sample suggests that these factors differentially contribute to development of melanoma even on a common genetic background of a germline CDKN2A mutation. Differences in melanoma risk across geographic regions justify the need for individual studies in each country before counseling should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.22712DOI Listing
August 2007

Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents.

J Med Genet 2007 Feb 11;44(2):99-106. Epub 2006 Aug 11.

Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892-7236, USA.

Background: The major factors individually reported to be associated with an increased frequency of CDKN2A mutations are increased number of patients with melanoma in a family, early age at melanoma diagnosis, and family members with multiple primary melanomas (MPM) or pancreatic cancer.

Methods: These four features were examined in 385 families with > or =3 patients with melanoma pooled by 17 GenoMEL groups, and these attributes were compared across continents.

Results: Overall, 39% of families had CDKN2A mutations ranging from 20% (32/162) in Australia to 45% (29/65) in North America to 57% (89/157) in Europe. All four features in each group, except pancreatic cancer in Australia (p = 0.38), individually showed significant associations with CDKN2A mutations, but the effects varied widely across continents. Multivariate examination also showed different predictors of mutation risk across continents. In Australian families, > or =2 patients with MPM, median age at melanoma diagnosis < or =40 years and > or =6 patients with melanoma in a family jointly predicted the mutation risk. In European families, all four factors concurrently predicted the risk, but with less stringent criteria than in Australia. In North American families, only > or =1 patient with MPM and age at diagnosis < or =40 years simultaneously predicted the mutation risk.

Conclusions: The variation in CDKN2A mutations for the four features across continents is consistent with the lower melanoma incidence rates in Europe and higher rates of sporadic melanoma in Australia. The lack of a pancreatic cancer-CDKN2A mutation relationship in Australia probably reflects the divergent spectrum of mutations in families from Australia versus those from North America and Europe. GenoMEL is exploring candidate host, genetic and/or environmental risk factors to better understand the variation observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jmg.2006.043802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2598064PMC
February 2007

Dermoscopy of lichenoid regressing seborrheic keratosis.

Arch Dermatol 2006 Mar;142(3):410

Hospital de Sant Pau i Santa Tecla, Tarragona, Spain.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/archderm.142.3.410DOI Listing
March 2006

[Presence of circulating cytomegalic cells in HIV negative immunosuppressed individuals following cytomegalovirus infection].

Biomedica 2005 Mar;25(1):129-35

Grupo de Inmunovirología, Corporación Biogenesis, Universidad de Antioquia, Medellín, Colombia.

Objective: Immunofluorenscence methods to detect pp65 antigenemia were implemented for identifying the circulating virus-infected cells in individuals known to have cytomegalovirus infection and disease symptoms.

Material And Methods: Between December-2002 and July-2003, 110 peripheral blood samples were obtained from 46 immunosuppressed patients. pp65 antigenemia and the presence of circulating cells were determined by indirect immunofluorescence using a commercial kit to detect CMV pp65 antigen in peripheral blood leukocytes. Antigenemia was positive when one or more cells was observed with multilobulated, homogenous fluorescent stain in the nucleus. The presence of infected circulating cells (peripheral blood mononuclear cells) was determined when an extended pattern of fluorescent stain was observed throughout the cytoplasm in cells of 35 to 50 microm.

Results: Eight antigenemias from 7 patients (15%) were positive. Of these, 4 (57%) were also positive for circulating infected cells and consisted of 3 kidney transplant recipients and 1 liver transplant recipient. The number of positive cells in antigenemia was greater in kidney-transplant recipients than in the rest of immunosupressed patients (457 vs. 1.96, p < 0.005). No association was seen between the presence of infected circulating cells, morbidity, mortality or the development of GVHD (p < 0.001).

Conclusion: No correlation was observed between the presence of infected cells, antigenemia and mortality. To substantiate the lack of correlation amongst these factors, prospective studies with larger sample sizes are necessary. These studies will aid in better defining the clinical application in immunosupressed patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2005

Role of the CDKN2A locus in patients with multiple primary melanomas.

J Clin Oncol 2005 May;23(13):3043-51

Dermatology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain.

Purpose: We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4.

Patients And Methods: One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included.

Results: Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM.

Conclusion: MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2005.08.034DOI Listing
May 2005

Small cell melanoma and ulceration as predictors of positive sentinel lymph node in malignant melanoma patients.

Melanoma Res 2004 Aug;14(4):277-82

Melanoma Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain.

Malignant melanoma (MM) early lymph node (LN) metastasis usually appears first in the sentinel LN (SLN). Breslow thickness is the main factor considered in the selection of patients to be submitted to SLN biopsy. The present study aimed to describe other independent prognostic factors useful in SLN candidate selection. During one year, 94 MM patients (90 primary cutaneous MM with Breslow thickness > or = 0.76 mm, and four cutaneous relapses), were submitted to SLN biopsy in the Melanoma Unit at the Hospital Clinic, Barcelona, Spain. The prognostic factors studied were: Breslow thickness, Clark's level of invasion, mitotic rate, cellular type (small, epithelioid, fusocellular, sarcomatoid), vertical growth phase, regression > 50%, severe vascularization, infiltrate (lymphocytic, plasmocytic), ulceration, neurotropism, intravascular/intraneural invasion, protein p16 expression and recurrence. Nineteen SLN (20.2%) were positive and 75 (79.8%) negative. No positive SLN occurred in MM with Breslow thickness < or = 1.0 mm. Breslow thickness > or = 2 mm (P = 0.005), severe vascularization (P = 0.005), small cell (P = 0.000) and ulceration (P = 0.005) were significant prognostic factors by univariate analysis. Small cell (P = 0.008) and ulceration (P = 0.05) were also significant prognostic factors in a multivariate analysis. The probability of finding a positive SLN for small cell was 56.9% [95% confidence interval (CI), 26.8-82.6%]. The probability of positive SLN for ulceration was 35.5% (95% CI, 14.2-64.7%). For small cell and ulceration together the probability increased to 86.3% (95% CI, 54.3-97.1%). The results of this study corroborated ulceration as a prognostic factor for SLN candidate selection and for the first time we have described small cell melanoma morphology as a significant factor associated with positive SLN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.cmr.0000136712.82910.a1DOI Listing
August 2004

Treatment of patients with progressive unresectable metastatic melanoma with a heterologous polyvalent melanoma whole cell vaccine.

Int J Cancer 2003 Sep;106(4):626-31

Department of Immunology, Hospital Clinic and IDIBAPS, Barcelona, Spain.

Unresectable metastatic melanoma has no elective treatment. Neither chemotherapy, intravenous IL-2 nor biochemotherapy clearly improves the overall survival. Recent assays with therapeutic vaccines have been recently yielded promising results. Here, we describe the application, clinical tolerance and antitumoural activity of a heterologous polyvalent melanoma whole cell vaccine in patients with metastatic melanoma. Twenty-eight AJCC stage III/IV melanoma patients with progressive unresectable metastatic disease were treated with our heterologous polyvalent melanoma whole cell vaccine between July 1, 1998 and July 1, 2002. All patients had already been unsuccessfully treated with high doses of IFN-alpha2 and/or polychemotherapy and/or biochemotherapy and/or perfusion of extremities, or could not receive other treatments due to their age or underlying illness. Twenty-three were assessable. The vaccine was constituted by 10 melanoma cell lines, derived from primary, lymph node and metastatic melanomas. Prior to intradermal inoculation, the cells were irradiated and mixed with BCG, and 50% were treated with DNFB. After a median follow-up of 19 months, 26% of patients responded: 3 CR (18, 16+, and 26+ months), 2 PR (8 and 22 months) and 1 MR (36+ months). The median survival of the whole group was 20.2 months. None of the 28 patients initially included in the study presented significant toxicity. This vaccination program had specific antitumoural activity in advanced metastatic melanoma patients and was well tolerated. The clinical responses and the median survival of our group of patients, together with the low toxicity of our polyvalent vaccine, suggest that this approach could be applied to earlier metastatic melanoma patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.11242DOI Listing
September 2003

Association between inherited thrombophilias, antiphospholipid antibodies, and lipoprotein A levels and venous thromboembolism in pregnancy.

Am J Perinatol 2003 Jan;20(1):17-24

Perinatology Unit, Morristown Memorial Hospital, New Jersey, USA.

The objective of this study is to evaluate the association between venous thromboembolism (VTE) in pregnancy with thrombophilic factors. Thirty pregnant women with VTE were compared with 30 pregnant women matched by age and race without VTE and evaluated for risk factors and thrombophilia. Statistical analysis used two-tailed Fisher's exact test. VTE distribution was 30% in first trimester, 9% in 2nd trimester, 26% in 3rd trimester and 35% postpartum. Seventeen (57%) of VTE cases versus 2 (7%) of control cases had specific thrombophilia diagnosis ( p <0.001). The results were: Factor V Leiden mutation (27 vs. 3%) p = 0.026, MTHFR homozygous 677 mutation (10 vs. 44%) p = 0.017, prothrombin gene mutation (11 vs. 0%), protein C deficiency (7 vs. 0%), antiphospholipid antibodies (27 vs. 3%) p = 0.026, mean lipoprotein levels 49 versus 23 mg/dL, p = 0.008, mean homocysteine levels 7.8 versus 7.1 umol/L. An association is suggested between thromboembolic events in pregnancy and thrombophilia, especially Factor V Leiden gene mutation and elevated antiphospholipid antibodies. A new finding is the association of elevated lipoprotein A levels with thromboembolic events in pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-2003-37947DOI Listing
January 2003
-->