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Summary: Blood plasma contains DNA fragments from dying cells, called cell‐free circulating DNA (cfDNA). In cancer patients, a fraction of their blood cfDNA comes from dying tumour cells. Therefore, key genetic alterations (mutations) from tumours might be detected in plasma from cancer patients. The analysis of cfDNA is a promising tool for the treating cancer patients, since the information from the tumour might be obtained from a blood sample, avoiding the use of 'invasive' methods such as tissue biopsies (samples taken by surgery, for example). Melanoma is an aggressive type of skin cancer. Each year more than 250,000 new cases are diagnosed worldwide. The p.V600E mutation in the BRAF gene (BRAFV600E) is detected in approximately 50% of melanomas. Currently, the analysis of the BRAFV600E mutation in plasma from melanoma patients can be used to monitor their disease progression. Besides tumours, the BRAFV600E mutation is frequently detected in moles on the skin, which are a risk factor to developing melanoma. To date, no information exists about the role of dying cells from moles in the detection of BRAFV600E in plasma. This study, from Spain, aimed to assess the robustness of the BRAFV600E test in plasma. The authors analysed plasma from 146 people without melanoma and from 33 melanoma patients with BRAFV600E melanomas. Melanomas are categorized from stage I to stage IV, with stage 1 as the earliest melanoma and stage IV as the most advanced. Stage I and II melanomas are present in the skin only and have not spread elsewhere in the body. Stage III have spread towards or have reached the draining lymph glands (nodes) and Stage IV melanomas are those that have spread beyond the closest draining lymph glands to other parts of the body. In this study, cell‐free circulating BRAFV600E was detected in 71% of patients with stage IV melanoma and 15% with stage III, whereas it was only detected in 1.4% of people without melanoma. The results of the BRAFV600E test in an individual were not influenced by the number of moles they had or clinical characteristics of moles (such as an unusual appearance). Additionally, they observed that melanoma patients with advanced disease showed a higher amount of BRAFV600E in plasma. Altogether, these findings indicate that the BRAFV600E test is an effective and robust tool for use with melanoma patients. This summary relates to the study: Detection of cell‐free circulating BRAFV600Eby droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance Linked Article: Calbet‐Llopart et al. Br J Dermatol 2020; 182:382–389 [ABSTRACT FROM AUTHOR]

Summary: Melanoma is an aggressive type of skin cancer. Each year more than 250,000 new cases are diagnosed worldwide. If diagnosed at early stages, melanoma can be cured with relatively simple surgery. Globally, 20% of melanoma patients will die, but when diagnosed with thick (more advanced / later stage) tumours, the probability of dying increases by up to 60%. The best strategy to improve survival is with early diagnosis. The identification of people at risk is essential. Around 10% of cases occur in a familial context. This means that these individuals have an inherited genetic risk of developing melanoma explained by the presence of alterations (mutations) in specific genes. In a family with known mutation, healthy individuals who carry the mutation can be included in early detection programs that allow the diagnosis of melanomas at early stages. But the gene/genes responsible for this risk is still unknown in more than 70% of families. This study, from Spain, aimed to evaluate the prevalence of mutations in two genes (POT1 and TERT) in Spanish melanoma‐prone families without known mutated genes. The authors sequenced (a way of studying) both genes in cases from 228 families. They found mutations in nearly 2% of the families assessed. They additionally identified two patients in two families who also had thyroid malignances. If this is confirmed in additional studies, the melanoma‐prone families with mutations in this gene will also benefit from early diagnosis of thyroid tumours. No mutations were identified in TERT promoter indicating that this gene does not play an important role in familial melanoma susceptibility in Spain. Linked Article: Potrony et al. Br J Dermatol 2019; 181:105–113 [ABSTRACT FROM AUTHOR]

Advancements in dermatological artificial intelligence research require high-quality and comprehensive datasets that mirror real-world clinical scenarios. We introduce a collection of 18,946 dermoscopic images spanning from 2010 to 2016, collated at the Hospital Clínic in Barcelona, Spain. The BCN20000 dataset aims to address the problem of unconstrained classification of dermoscopic images of skin cancer, including lesions in hard-to-diagnose locations such as those found in nails and mucosa, large lesions which do not fit in the aperture of the dermoscopy device, and hypo-pigmented lesions. Our dataset covers eight key diagnostic categories in dermoscopy, providing a diverse range of lesions for artificial intelligence model training. Furthermore, a ninth out-of-distribution (OOD) class is also present on the test set, comprised of lesions which could not be distinctively classified as any of the others. By providing a comprehensive collection of varied images, BCN20000 helps bridge the gap between the training data for machine learning models and the day-to-day practice of medical practitioners. Additionally, we present a set of baseline classifiers based on state-of-the-art neural networks, which can be extended by other researchers for further experimentation., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest None disclosed.

Background: CDKN2A, CDK4, and POT1 are well-established melanoma-susceptibility genes., Objective: We evaluated melanoma histopathology for individuals with germline mutations of CDKN2A, CDK4, and POT1., Methods: We assessed histopathology for melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) from the United States, Italy, and Spain. Comparisons between mutation carriers and noncarriers (no mutation) were adjusted for age, sex, Breslow depth, and correlations among individuals within the same family., Results: Histologic slides were evaluated for 290 melanomas (139 from 132 noncarriers, 122 from 68 CDKN2A carriers, 10 from 6 CDK4 carriers, and 19 from 16 POT1 carriers). Superficial spreading was the predominant subtype for all groups. Spitzoid morphology (>25% of tumor) was observed in 10 of 15 invasive melanomas (67%) from POT1 carriers (P < .0001 vs noncarriers). This finding was independently confirmed by 3 expert melanoma dermatopathologists in 9 of 15 invasive melanomas (60%). In situ and invasive melanomas from CDKN2A and CDK4 carriers were histologically similar to melanomas from noncarriers., Limitations: Limited sample sizes for rare melanoma-susceptibility syndromes (CDK4, POT1)., Conclusion: Spitzoid morphology was associated with POT1 mutations suggesting that telomere dysfunction (POT1 mutations) may contribute to spitzoid differentiation in melanocytic tumors., (Published by Elsevier Inc.)

Congenital melanocytic nevi (CMN) are cutaneous malformations whose prevalence is inversely correlated with projected adult size. CMN are caused by somatic mutations, but epidemiological studies suggest that germline genetic factors may influence CMN development. In CMN patients from the U.K., genetic variants in MC1R, such as p.V92M and loss-of-function variants, have been previously associated with larger CMN. We analyzed the association of MC1R variants with CMN characteristics in two distinct cohorts of medium-to-giant CMN patients from Spain (N = 113) and from France, Norway, Canada, and the United States (N = 53), similar at the clinical and phenotypical level except for the number of nevi per patient. We found that the p.V92M or loss-of-function MC1R variants either alone or in combination did not correlate with CMN size, in contrast to the U.K. CMN patients. An additional case-control analysis with 259 unaffected Spanish individuals showed a higher frequency of MC1R compound heterozygous or homozygous variant genotypes in Spanish CMN patients compared to the control population (15.9% vs. 9.3%; p = .075). Altogether, this study suggests that MC1R variants are not associated with CMN size in these non-UK cohorts. Additional studies are required to define the potential role of MC1R as a risk factor in CMN development., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acenocoumarol is an oral anticoagulant with significant interindividual dose variations. Variants in CYP2C9 and VKORC1 have been associated with acenocoumarol maintenance dose. We analysed whether any of the 49 polymorphisms in CYP2C9 and VKORC1 previously associated with acenocoumarol maintenance dose in a Genome-Wide Association study (GWAs) in Dutch population are associated with stroke recurrence, intracranial haemorrhage (ICH) and acenocoumarol maintenance dose in a Spanish population. We performed a GWAs using Human Core Exome-chip (Illumina) in 78 patients stroke patients treated with acenocoumarol for secondary prevention enrolled as part of the prospective investigator-initiated study (IIS) SEDMAN Study. Patients were followed-up a median of 12.8 months. Three and eight patients had recurrent stroke and ICH events, respectively. We found 14 of the 49 published variants associated with acenocoumarol maintenance dose (p < 0.05). Six polymorphisms were associated with stroke recurrence and four variants with ICH (p < 0.05). In conclusion, variants in VKORC1 and CYP2C9 are associated with acenocoumarol maintenance dose, stroke recurrence and ICH in a Spanish cohort. These results highlight the relevance of studying pharmacogenetics associated with efficacy and safety of anticoagulant drugs and justify studies with larger sample size and different ethnic populations.

Background: There is no consensus on the imaging tests that should be performed at the initial staging of melanoma patients., Objective: To evaluate the diagnostic accuracy of 4 imaging studies for the initial staging of melanoma patients., Methods: Cross-sectional study with prospectively collected data, from January 2011 to April 2017, including patients with clinical stage T2b to T4b according to 2009 American Joint Committee on Cancer, without evidence of metastasis., Results: Initial staging of 308 patients detected 16.6% of metastases and 5.8% false-positive results, overall. Regional lymph node ultrasonography showed a metastasis detection rate (MDR) of 12.8%, false-positive rate of 0.8%, and accuracy of 96.0%. Computed tomography (CT) and positron emission tomography-CT had the highest detection rates at stage T4b: MDR, 13.3%; false-positive rate, 8.9%; accuracy, 91.1%; and MDR, 6.9%; false-positive rate, 0%; and accuracy, 93.1%, respectively. Brain magnetic resonance imaging showed a MDR of 2.0% in T4b., Limitations: Single-center study., Conclusion: Performing ultrasound scans for assessing lymph node metastasis in patients with American Joint Committee on Cancer T2b stage and above is advisable. In patients with stage T4b, CT or positron emission tomography-CT are suitable for the detection of metastasis. Brain magnetic resonance imaging at T4b deserves further discussion, considering the ultimate clinical benefit in management and therapeutic options for asymptomatic patients., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: The prevalence of postoperative hypoparathyroidism has been studied in registries and in surgical series with highly variable and imprecise results. However, the frequency of this hormonal deficiency in the clinical practice of endocrinologists is not known with accuracy. We aimed to assess the prevalence and risk factors of hypoparathyroidism in patients undergoing total thyroidectomy in Spain., Methods: We designed a retrospective, multicentre and nation-wide protocol including all patients with total thyroidectomy who were seen in the endocrinology clinic of the participant centers from January to March 2018. Prevalence of hypoparathyroidism was evaluated at discharge of surgery, 3-6 months after surgery, 12 months after surgery and at last visit. Twenty hospitals participated in the study., Results: Of 1792 patients undergoing total thyroidectomy, 866 (48.3%) developed postoperative hypoparathyroidism at discharge of surgery. Most of them recover parathyroid function over time. Prevalence of hypoparathyroidism at 3-6 months, 12 months and at last visit was 22.9%, 16.7% and 14.5%, respectively. The risk of developing definitive hypoparathyroidism was related to the presence of parathyroid tissue at histology, lymph node dissection, and two-stage thyroidectomy. Patients with thyroid cancer, with higher postoperative calcium levels and treated by expert surgical teams exhibited lower risk of developing permanent hypoparathyroidism., Conclusions: Although most patients with postsurgical hypoparathyroidism recover parathyroid function, the prevalence of permanent disease in clinical practice is non negligible (14.5%). Postoperative calcium, extent and timing of surgery, the presence of cancer, expert surgical team, and parathyroid tissue at histology are predictors of permanent hypoparathyroidism.

Objective: To validate the Genot-PA score, a clinical-genetic logistic regression score that stratifies the thrombolytic therapy safety, in a new cohort of patients with stroke., Methods: We enrolled 1,482 recombinant tissue plasminogen activator (rtPA)-treated patients with stroke in Spain and Finland from 2003 to 2016. Cohorts were analyzed on the basis of ethnicity and therapy: Spanish patients treated with IV rtPA within 4.5 hours of onset (cohort A and B) or rtPA in combination with mechanical thrombectomy within 6 hours of onset (cohort C) and Finnish participants treated with IV rtPA within 4.5 hours of onset (cohort D). The Genot-PA score was calculated, and hemorrhagic transformation (HT) and parenchymal hematoma (PH) risks were determined for each score stratum., Results: Genot-PA score was tested in 1,324 (cohort A, n = 726; B, n = 334; C, n = 54; and D, n = 210) patients who had enough information to complete the score. Of these, 213 (16.1%) participants developed HT and 85 (6.4%) developed PH. In cohorts A, B, and D, HT occurrence was predicted by the score ( p = 2.02 × 10 -6 , p = 0.023, p = 0.033); PH prediction was associated in cohorts A through C ( p = 0.012, p = 0.034, p = 5.32 × 10 -4 ). Increased frequency of PH events from the lowest to the highest risk group was found (cohort A 4%-15.7%, cohort B 1.5%-18.2%, cohort C 0%-100%). The best odds ratio for PH prediction in the highest-risk group was obtained in cohort A (odds ratio 5.16, 95% confidence interval 1.46-18.08, p = 0.009)., Conclusion: The Genot-PA score predicts HT in patients with stroke treated with IV rtPA. Moreover, in an exploratory study, the score was associated with PH risk in mechanical thrombectomy-treated patients., (© 2019 American Academy of Neurology.)

Background: Germline mutations in telomere-related genes such as POT1 and TERT predispose individuals to familial melanoma., Objectives: To evaluate the prevalence of germline mutations in POT1 and TERT in a large cohort of Spanish melanoma-prone families (at least two affected first- or second-degree relatives)., Methods: Overall, 228 CDKN2A wild-type melanoma-prone families were included in the study. Screening of POT1 was performed in one affected person from each family and TERT was sequenced in one affected patient from 202 families (26 families were excluded owing to DNA exhaustion/degradation). TERT promoter sequencing was extended to an additional 30 families with CDKN2A mutation and 70 patients with sporadic multiple primary melanoma (MPM) with a family history of other cancers., Results: We identified four families with potentially pathogenic POT1 germline mutations: a missense variant c.233T>C (p.Ile78Thr); a nonsense variant c.1030G>T (p.Glu344*); and two other variants, c.255G>A (r.125&#95;255del) and c.1792G>A (r.1791&#95;1792insAGTA, p.Asp598Serfs*22), which we confirmed disrupted POT1 mRNA splicing. A TERT promoter variant of unknown significance (c.-125C>A) was detected in a patient with MPM, but no germline mutations were detected in TERT promoter in cases of familial melanoma., Conclusions: Overall, 1·7% of our CDKN2A/CDK4-wild type Spanish melanoma-prone families carry probably damaging mutations in POT1. The frequency of TERT promoter germline mutations in families with melanoma in our population is extremely rare., (© 2018 British Association of Dermatologists.)

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.

Importance: The main high-penetrance melanoma susceptibility gene is CDKN2A, encoding p16INK4A and p14ARF. The gene MITF variant p.E318K also predisposes to melanoma and renal cell carcinoma. To date, the prevalence of MITF p.E318K and its clinical and phenotypical implications has not been previously assessed in a single cohort of Spanish patients with melanoma or in p16INK4A mutation carriers., Objectives: To evaluate the prevalence of MITF p.E318K in Spanish patients with melanoma and assess the association with clinical and phenotypic features., Design, Setting, and Participants: A hospital-based, case-control study was conducted at the Melanoma Unit of Hospital Clinic of Barcelona, with MITF p.E318K genotyped in all patients using TaqMan probes. We included 531 patients: 271 patients with multiple primary melanoma (MPM) without mutations affecting p16INK4A (wild-type p16INK4A); 191 probands from melanoma-prone families with a single melanoma diagnosis and without mutations affecting p16INK4A, and 69 probands from different families carrying CDKN2A mutations affecting p16INK4A. A population-based series of 499 age- and sex-matched cancer-free individuals from the Spanish National Bank of DNA were included as controls. Patients were recruited between January 1, 1992, and June 30, 2014; data analysis was conducted from September 1 to November 30, 2014., Main Outcomes and Measures: The genetic results of the MITF p.E318K variant were correlated with clinical and phenotypic features., Results: Among the 531 patients, the prevalence of the MITF p.E318K variant was calculated among the different subsets of patients included and was 1.9% (9 of 462) in all melanoma patients with wild-type p16INK4A, 2.6% (7 of 271) in those with MPM, and 2.9% (2 of 69) in the probands of families with p16INK4A mutations. With results reported as odds ratio (95% CI), the MITF p.E318K was associated with an increased melanoma risk (3.3 [1.43-7.43]; P < .01), especially in MPM (4.5 [1.83-11.01]; P < .01) and high nevi count (>200 nevi) (8.4 [2.14-33.19]; P < .01). Two fast-growing melanomas were detected among 2 MITF p.E318K carriers during dermatologic digital follow-up., Conclusions and Relevance: In addition to melanoma risk, MITF p.E318K is associated with a high nevi count and could play a role in fast-growing melanomas. Testing for MITF p.E318K should not exclude patients with known mutations in p16INK4A. Strict dermatologic surveillance, periodic self-examination, and renal cell carcinoma surveillance should be encouraged in this context.

HIV-1 exhibits a characteristically high genetic diversity, with the M group, responsible for the pandemic, being classified into nine subtypes, 72 circulating recombinant forms (CRFs) and numerous unique recombinant forms (URFs). Here we characterize the near full-length genome sequence of an HIV-1 BG intersubtype recombinant virus (X3208) collected in Galicia (Northwest Spain) which exhibits a mosaic structure coincident with that of a previously characterized BG recombinant virus (9601&#95;01), collected in Germany and epidemiologically linked to Portugal, and different from currently defined CRFs. Similar recombination patterns were found in partial genome sequences from three other BG recombinant viruses, one newly derived, from a virus collected in Spain, and two retrieved from databases, collected in France and Portugal, respectively. Breakpoint coincidence and clustering in phylogenetic trees of these epidemiologically-unlinked viruses allow to define a new HIV-1 CRF (CRF73&#95;BG). CRF73&#95;BG shares one breakpoint in the envelope with CRF14&#95;BG, which circulates in Portugal and Spain, and groups with it in a subtype B envelope fragment, but the greatest part of its genome does not appear to derive from CRF14&#95;BG, although both CRFs share as parental strain the subtype G variant circulating in the Iberian Peninsula. Phylogenetic clustering of partial pol and env segments from viruses collected in Portugal and Spain with X3208 and 9691&#95;01 indicates that CRF73&#95;BG is circulating in both countries, with proportions of around 2-3% Portuguese database HIV-1 isolates clustering with CRF73&#95;BG. The fact that an HIV-1 recombinant virus characterized ten years ago as a URF has been shown to represent a CRF suggests that the number of HIV-1 CRFs may be much greater than currently known.

Introduction: In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumour and sentinel-node biopsy. The objective of this study is to analyse the prognostic implications of this delay., Patients and Method: This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival., Results: A delay time of 40 days or less (hazard ratio (HR), 1.7; confidence interval (CI), 1.2-2.5) increased Breslow thickness (Breslow ⩾ 2 mm, HR, > 3.7; CI, 1.4-10.7), ulceration (HR, 1.6; CI, 1.1-2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9-4.2), and primary melanoma localised in the head or neck were independently associated with worse melanoma-specific survival (all P < 0.03). The stratified analysis showed that the effect of delay time was at the expense of the patients with a negative sentinel-node biopsy and without regression., Conclusion: Early sentinel-node biopsy is associated with worse survival in patients with cutaneous melanoma., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

All cases of MM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007 were recorded and melanoma incidence calculated and adjusted for the European standard population via the direct method. The age standardised rate/100,000 inhabitants varied from 6.74 in 2000 to 8.64 in 2007 for all melanomas and from 4.79 to 5.80 for invasive MMs; the Breslow thickness was stable during the period. The increase in invasive melanoma incidence in the elderly was remarkable, the crude rate/100,000 inhabitants increasing from 11.04 (2000) to 15.49 (2007) in the 60-64 year population, while remaining more stable in the 30-34 year range, from 3.97 in 2000 to 4.55 in 2007, and with a tendency to decrease from 5.1 in 2000 to 2.5 in 2007 for the age range of 25-29 years. These lower age ranges are much more affected by immigration. Despite the large immigrant population (nearly one million immigrants arrived in Catalonia during the study period from countries with a low melanoma incidence), melanoma incidence in our region has risen considerably and this trend is likely to persist in the near future.

Background: Cyclin-dependent kinase inhibitor 2A (CDKN2A) is the major high-risk susceptibility gene for melanoma., Objective: We sought to evaluate the effect of CDKN2A mutations in Spanish patients with a high risk of developing melanoma and the association with clinical and family history features., Methods: A cross-sectional study design was used to analyze the CDKN2A impact in 702 Spanish patients with a high risk of developing melanoma., Results: The CDKN2A mutation prevalence was 8.5% in patients with sporadic multiple primary melanoma and 14.1% in familial melanoma. Number of cases in the family, number of primary melanomas, and age of onset were associated with the presence of CDKN2A mutation. Having a CDKN2A mutation in the family increased the prevalence of other cancers (prevalence ratio [PR] 2.99, P=.012) and prevalence of pancreatic (PR 2.97, P=.006), lung (PR 3.04, P<.001), and breast (PR 2.19, P=.018) cancers but not nephrourologic or colon cancer., Limitations: Smoking status was not assessed in the individuals with lung cancer., Conclusions: Melanoma-prone families with mutations in CDKN2A have an increased prevalence of a broad spectrum of cancers including lung, pancreatic, and breast cancer. This information should be included in genetic counseling and cancer prevention programs for CDKN2A mutation carriers., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Cutaneous leishmaniasis is widely distributed, Spain being a hypoendemic region. Noninvasive bedside detection of the histopathologic response to the intracellular organism that allows rapid diagnosis and prompt therapy could be the ideal tool to manage a commonly self-healing lesion. Confocal microscopy is a technique which allows in vivo examination of the skin at cellular resolution., Methods: We describe the in vivo confocal microscopic features of cutaneous leishmaniasis, finding a correlation with dermoscopy and histopathology., Conclusions and Relevance: This case illustrates the capability of confocal microscopy to characterize the cutaneous infection by Leishmania organisms and to perform a noninvasive diagnosis., (© 2014 S. Karger AG, Basel.)

Background: Serum 25-hydroxyvitamin D3 (Vitamin D) insufficiency and single-nucleotide polymorphisms (SNPs) on its receptor, Vitamin D receptor (VDR), have been reported to be involved in melanoma susceptibility in populations mostly from northern countries., Objective: To investigate 25-hydroxyvitamin D3 levels and VDR SNPs in melanoma patients from sunny area of Barcelona, two studies were carried out. The first study evaluated the levels of Vitamin D at time of melanoma diagnosis and the second one analyzed the association between VDR genetic variants and risk of having a high nevus number, the strongest phenotypic risk factor for melanoma., Methods: The levels of 25-hydroxyvitamin D3 in 81 melanoma patients at diagnosis were measured. In a second group of melanoma patients, including 150 with low and 113 with high nevus number, 11 VDR SNPs were analyzed for their association with nevus number., Results: In the first study, 68% of patients had insufficient levels of 25-hydroxyvitamin D3 (<25 ng/ml). Autumn-winter months and fair phototype were associated with 25-hydroxyvitamin D3 insufficiency; after multivariate analysis, season of sampling remained the only independent predictor of 25-hydroxyvitamin D3 levels. In the second study, VDR variant rs2189480 (P = 0.006) was associated with risk of high nevus number whereas rs2239179 (P = 0.044) and rs7975128 (P = 0.0005) were protective against high nevus number. After Bonferroni adjustment only rs7975128 remained significant. In stratified analysis, SNP rs7975128 was found protective against multiple melanomas (P = 0.021)., Conclusion: This study showed that even in Barcelona, a sunny Mediterranean area, 25-hydroxyvitamin D3 levels were sub-optimal in the majority of melanoma patients at diagnosis. The involvement of VDR in nevi and, in turn, in melanoma susceptibility has also been suggested. Larger studies are needed to confirm our findings.

Pigmented spindle cell nevus (PSCN), also known as Reed nevus, is a distinctive melanocytic tumor that can show worrisome clinical and histologic features mimicking a malignant melanoma. From a series of 46 pigmented spindle cell melanocytic lesions, including 22 PSCN and 24 spindle cell malignant melanomas (SCMMs), we collected clinical and histopathologic characteristics and evaluated cell cycle and apoptosis regulators by immunohistochemistry. Moreover, fluorescence in situ hybridization (FISH) using probes targeting 6p25 (RREB1), 11q13 (CCND1), 6q23 (MYB), and centromere 6 was performed. PSCN presented in younger people, frequently in women, and were small lesions under 7 mm in diameter affecting the lower limbs, whereas SCMMs arose more frequently in the trunk, upper limbs, and head and neck region. Histologically, symmetry, good lateral demarcation, and uniformity of cellular nests were significantly differential features of PSCN, whereas pagetoid and adnexal spread were frequently seen in both tumors. Immunohistochemical markers that significantly differed from melanomas were Ki-67, cyclin D1, and survivin. FISH was positive in 1 of 15 PSCN and was negative in 4 of 15 SCMMs. These results correlated to a sensitivity of 73% and a specificity of 93%. In conclusion, in the evaluation of pigmented spindle cell melanocytic tumors, the integration of clinical and histologic assessment is essential. However, ancillary techniques such as proliferation antigen Ki-67, cyclin D1, survivin, and FISH can be useful as adjunctive tools.

Objectives: To analyze the incidence, clinical and histopathological manifestations, surgical complications, and prognostic factors of thyroid cancer in the east Madrid population., Patients and Methods: Retrospective analysis of 141 consecutive diagnosed of thyroid cancer in our area between 1985 and 2001. Median follow-up was 4,5 years., Results: The annual incidence rate was 4.74/100,000 inhabitants and the female:male proportion 3.5:1. The average age of patients at diagnosis was 44.5 years and nodular goiter was the principal type of clinical presentation (74.5%). The most frequent histological variant was papillary thyroid carcinoma (69%). Total thyroidectomy was carried out in 86% patients. 9.6% patients suffered permanent hypoparathyroidism and 3.3% paralysis of recurrent laryngeal nerve. Radioactive iodine ablation of remaining thyroid was carried out in 91 patients. Residual disease or local recurrence was observed on follow-up in 21% of patients, and metastasis at a distant site in 9%. 7.9% died along follow-up. The principal prognostic factors for metastasis or death were age, histological type, tumor size, local invasion and existence of metastasis at the time of diagnosis., Conclusions: The incidence of thyroid cancer in our population was high, especially in women. Although the proportion of postsurgical complications was elevated, global prognosis is good and some factors related to it have been identified. Increase of thyroglobulin plasma level at follow-up is a good recurrence indicator of the disease, especially with regard to distant metastases.

Objective: To find the attitudes and expectations of doctors during the process of computerising primary care (PC)., Design: Qualitative investigation through discussion groups., Participants: Thirty-one doctors from the two PC regions of Gipuzkoa., Method: Intentional stratified sampling by regions and by experience in using a computer in the consulting-room. Five discussion groups with recording and transcription of the contents with prior authorisation and guarantee of confidentiality. Qualitative analysis of the notes and transcriptions with the help of computer back-up. Validation through sending of results to participants and discussion between the authors., Results: Introducing computers into PC consulting-rooms had repercussions both on the ordering and contents of the information recorded. The effort <> was not accompanied by subsequent evaluation. Notable deficiencies in management of the computerising process were perceived. Computer use created additional symbolic effects for both patients and doctors., Conclusions: Computerising PC is a process whose repercussions on medical care are far from neutral and so require rigorous discussion and evaluation. Defining step-by-step and measurable objectives, transparency in management and the promotion of evaluative research would all favour the effective development of projects to computerise PC.