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Echeverria B.,Instituto Valenciano Of Oncologia | Bulliard J.-L.,University of Lausanne | Guillen C.,Instituto Valenciano Of Oncologia | Nagore E.,Instituto Valenciano Of Oncologia | Nagore E.,San Vicente Mártir Catholic University of Valencia
British Journal of Dermatology | Year: 2014

Background The presence of multiple melanocytic naevi is a strong risk factor for melanoma. Use of the whole body naevus count to identify at-risk patients is impractical. Objectives To (i) identify a valid anatomical predictor of total naevus count; (ii) determine the number of naevi that most accurately predict total naevus count above 25, 50 and 100; and (iii) evaluate determinants of multiple melanocytic naevi and atypical naevi. Methods Clinical data from 292 consecutive Spanish patients consulting for skin lesions requiring debriding were collected throughout 2009 and 2010. Correlations between site-specific and whole body naevus counts were analysed. Cut-offs to predict total naevus counts were determined using the area under the receiver operating characteristic curve. Results The studied population was young (median age 31 years, interquartile range 28-43). The naevus count on the right arm correlated best with the total nevus count (R2 0·80 for men, 0·86 for women). Presence of at least five naevi on the right arm was the strongest determinant of a total naevus count above 50 [odds ratio (OR) 34·4, 95% confidence interval (CI) 13·9-85·0] and of having at least one atypical naevus (OR 5·7, 95% CI 2·4-13·5). Cut-off values of 6, 8 and 11 naevi on the right arm best predicted total naevus count above 25, 50 and 100, respectively. Conclusions Our results support the arm as a practical and reliable site to estimate the total naevus count when screening or phenotyping large populations. Threshold values for the number of naevi on the arm are proposed to help identify patients for melanoma screening. What's already known about this topic? In order to phenotype or identify at-risk patients in a rapid and practical manner for large-scale studies or screening campaigns, naevus counts on selected body sites can be used as a proxy for total body naevus count. The correlation between site-specific and total body naevus counts appears to be highest for the arms, although results have not been consistent across studies or sexes. What does this study add? Our results further support the arm as a practical and reliable site to estimate the total naevus count when screening or phenotyping large populations. Cut-off values of 6, 8 and 11 naevi on the right arm best predicted total naevus count above 25, 50 and 100, respectively. These threshold values provide dermatologists with various degrees of patient risk selection and can be adjusted on an individual basis. © 2013 British Association of Dermatologists.


Requena L.,Autonomous University of Madrid | Requena C.,Instituto Valenciano Of Oncologia | Christensen L.,Copenhagen University | Kutzner H.,Dermatopathologische Gemeinschaftspraxis | Cerroni L.,University of Graz
Journal of the American Academy of Dermatology | Year: 2011

In recent years, injections with filler agents are often used for wrinkle-treatment and soft tissue augmentation by dermatologists and plastic surgeons. Unfortunately, the ideal filler has not yet been discovered and all of them may induce adverse reactions. Quickly biodegradable or resorbable agents may induce severe complications, but they will normally disappear spontaneously in a few months. Slowly biodegradable or nonresorbable fillers may give rise to severe reactions that show little or no tendency to spontaneous improvement. They may appear several years after the injection, when the patient does not remember which product was injected, and treatment is often insufficient. In this review, we discuss the most commonly used fillers, their most frequent adverse reactions as well as the characteristic histopathologic findings that allow the identification of the injected filler agent. In conclusion, histopathologic study remains as the gold standard technique to identify the responsible filler. Learning objectives: After completing this learning activity, participants should be able to recognize the most frequent adverse reactions induced by cosmetic fillers, identify their histopathologic characteristics so that they can be distinguished from each other, and advise their patients with adverse reactions about the different nature of these according to the filler for subsequent successful treatment. © 2009 by the American Academy of Dermatology, Inc.


Gianni L.,San Raffaele Hospital | Eiermann W.,Interdisziplinares Onkologisches Zentrum Munich | Semiglazov V.,NN Petrov Research Institute of Oncology | Lluch A.,University of Valencia | And 16 more authors.
The Lancet Oncology | Year: 2014

Background: In our randomised, controlled, phase 3 trial NeOAdjuvant Herceptin (NOAH) trial in women with HER2-positive locally advanced or inflammatory breast cancer, neoadjuvant trastuzumab significantly improved pathological complete response rate and event-free survival. We report updated results from our primary analysis to establish the long-term benefit of trastuzumab-containing neoadjuvant therapy. Methods: We did this multicentre, open-label, randomised trial in women with HER2-positive locally advanced or inflammatory breast cancer. Participants were randomly assigned (1:1), by computer program with a minimisation technique, to receive neoadjuvant chemotherapy alone or with 1 year of trastuzumab (concurrently with neoadjuvant chemotherapy and continued after surgery). A parallel group with HER2-negative disease was included and received neoadjuvant chemotherapy alone. Our primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered at www.controlled-trials.com, ISRCTN86043495. Findings: Between June 20, 2002, and Dec 12, 2005, we enrolled 235 patients with HER2-positive disease, of whom 118 received chemotherapy alone and 117 received chemotherapy plus trastuzumab. 99 additional patients with HER2-negative disease were included in the parallel cohort. After a median follow-up of 5·4 years (IQR 3·1-6·8) the event-free-survival benefit from the addition of trastuzumab to chemotherapy was maintained in patients with HER2-positive disease. 5 year event-free survival was 58% (95% CI 48-66) in patients in the trastuzumab group and 43% (34-52) in those in the chemotherapy group; the unadjusted hazard ratio (HR) for event-free survival between the two randomised HER2-positive treatment groups was 0·64 (95% CI 0·44-0·93; two-sided log-rank p=0·016). Event-free survival was strongly associated with pathological complete remission in patients given trastuzumab. Of the 68 patients with a pathological complete response (45 with trastuzumab and 23 with chemotherapy alone), the HR for event-free survival between those with and without trastuzumab was 0·29 (95% CI 0·11-0·78). During follow-up only four cardiovascular adverse events were regarded by the investigator to be drug-related (grade 2 lymphostasis and grade 2 lymphoedema, each in one patient in the trastuzumab group, and grade 2 thrombosis and grade 2 deep vein thrombosis, each in one patient in the chemotherapy-alone group). Interpretation: These results show a sustained benefit in event-free survival from trastuzumab-containing neoadjuvant therapy followed by adjuvant trastuzumab in patients with locally advanced or inflammatory breast cancer, and provide new insight into the association between pathological complete remission and long-term outcomes in HER2-positive disease. Funding: F Hoffmann-La Roche. © 2014 Elsevier Ltd.


Heidenreich B.,German Cancer Research Center | Nagore E.,University of Valencia | Rachakonda P.S.,German Cancer Research Center | Garcia-Casado Z.,Instituto Valenciano Of Oncologia | And 6 more authors.
Nature communications | Year: 2014

We previously reported a disease segregating causal germline mutation in a melanoma family and recurrent somatic mutations in metastasized tumours from unrelated patients in the core promoter region of the telomerase reverse transcriptase (TERT) gene. Here we show that the TERT promoter mutations, besides causing an increased gene expression, associate with increased patient age, increased Breslow thickness and tumour ulceration in 287 primary melanomas. The mutations are more frequent at both intermittently and chronically sun-exposed sites than non-exposed sites and tend to co-occur with BRAF and CDKN2A alterations. The association with parameters generally connected with poor outcome, coupled with high recurrence and mechanistic relevance, raises the possibility of the eventual use of TERT promoter mutations in the disease management.


Llombart B.,Instituto Valenciano Of Oncologia | Serra-Guillen C.,Instituto Valenciano Of Oncologia | Monteagudo C.,University of Valencia | Lopez Guerrero J.A.,Instituto Valenciano Of Oncologia | Sanmartin O.,Instituto Valenciano Of Oncologia
Seminars in Diagnostic Pathology | Year: 2013

Dermatofibrosarcoma protuberans (DFSP) is a rare superficial tumor characterized by high rates of local recurrence and low risk of metastasis. DFSP occurs most commonly on the trunk and proximal extremities, affects all races, and often develops between the second and fifth decade of life. The tumor grows slowly, typically over years. Histologically, several variants of DFSP have been described and should be well characterized to avoid misdiagnosis with other tumors. These include pigmented (Bednar tumor), myxoid, myoid, granular cell, sclerotic, atrophic DFSP, giant cell fibroblastoma, and DFSP with fibrosarcomatous areas. Of all these variants, only the DFSP with fibrosarcomatous areas is high grade, with a higher rate of local recurrence and distant metastasis. DFSP is genetically characterized by the t(17;22)(q22;q13), resulting in the fusion of alpha chain type 1 of collagen gene and platelet-derived growth factor beta gene. This translocation is present in 90% of DFSP and represents a very useful tool in the differential diagnosis of DFSP with other tumors with similar histology. The standard treatment is wide local excision with at least a 2-cm margin. However, local recurrence after apparently adequate surgical excision is well recognized. Mohs micrographic surgery would be the treatment of choice with a better cure rate and maximal conservation of tissue. When surgery is insufficient, clinical evidence has suggested that imatinib mesylate is a safe and effective treatment in DFSP, especially in cases of local advanced or metastatic disease. This article presents an overview of the state of the art in the clinicopathological management of this disease. © 2013 Elsevier Inc.


Barnadas A.,Hospital Santa Creu i Sant Pau | Vazquez C.,Instituto Valenciano Of Oncologia
Breast Cancer Research and Treatment | Year: 2010

Breast cancer is the leading cause of death in women under 30 years of age. In young women, breast tumors usually exhibit more aggressive features then their older counterparts, including larger tumor size, a higher incidence of poorly differentiated tumors, positive lymph nodes, high proliferation rates, higher incidence of HER2, a higher prevalence of basal-like histologic subtype, and the absence of endocrine receptors. After age, positive family history for breast cancer is among the highest risk factors for developing the disease. Approximately, 5-10% of breast cancers is considered directly related to inherited mutations in BRCA1/BRCA2 genes. Women carrying these mutations have a lifetime risk of breast cancer of 60-80%. Thus, genetic screening at the time of diagnosis is warranted in order to undertake opportune prophylactic measures. Digital mammography is the gold-standard for the diagnosis of breast cancer. However, due to particularities of the breast tissue in young women, ultrasound and magnetic resonance imaging are the preferred methods to diagnose no palpable breast lesions and to further characterize mammographic findings. Nonetheless, even if imaging studies are negative, suspicious breast masses should be biopsied under MRI or ultrasound guidance. © 2010 Springer Science+Business Media, LLC.


Martorell-Calatayud A.,Hospital Of Manises | Sanmartin Jimenez O.,Instituto Valenciano Of Oncologia | Cruz Mojarrieta J.,Instituto Valenciano Of Oncologia | Guillen Barona C.,Instituto Valenciano Of Oncologia
Actas Dermo-Sifiliograficas | Year: 2013

With a lifetime incidence of approximately 10% in the general population, cutaneous squamous cell carcinoma (CSCC) is the second most common type of nonmelanoma skin cancer. Most CSCCs are benign and can be completely eradicated by surgery or other dermatological procedures. There is, however, a subgroup associated with an increased likelihood of lymph node metastases and, therefore, with high morbidity and mortality. This article analyzes the various factors that define aggressive CSCC. We propose a method for defining high-risk SCC on the basis of a series of major and minor criteria. This method will allow better prognostic evaluation and enable personalized management of patients with high-risk SCC, possibly leading to improved overall survival. © 2012 Elsevier España, S.L. y AEDV. Todos los derechos reservados.


Padilla Alarcon J.,Instituto Valenciano Of Oncologia | Penalver Cuesta J.C.,Instituto Valenciano Of Oncologia
Archivos de Bronconeumologia | Year: 2013

Introduction: This paper intends to assess the influence of a fast-track surgery program on hospital stay and morbidity/mortality in lung resection surgery. Patients and methods: A prospective study including 100 patients who underwent open lung resection due to neoplastic pathologies. The variables analyzed were demographic, clinical, resection type, length of hospital stay and postoperative complications, adjusting these to the classification established according to the treatment required. Results: Seventy-three patients were men, and mean age was 60.8. 82% of the subjects were asymptomatic, 97% had a history of smoking and the majority presented associated comorbidities. The resection types included 7 pneumonectomies, 79 lobectomies, 6 bilobectomies and 8 segmentectomies. Mean hospital stay was 5.4 ± 4.2 days (range: 3-23), varying between 3.4 ± 0.8 days (range: 3-6) and 9.8 ± 5.3 days (range: 4-23) according to the absence or presence of complications. Associated mortality was 2% and morbidity 31%; the most frequent complications were persistent air leak (10%) and atrial fibrillation (6%). 51.5% of the complications were classified within the lower grade complication group, depending on treatment required. Four patients required readmittance after hospital discharge. Conclusions: Fast-track surgery programs are able to reduce hospitalization times by planning a multidisciplinary strategy of the surgical procedure, in which the patient him/herself participates. It is equally necessary to establish systems to classify postoperative complications that can evaluate the quality of the surgery. © 2012 SEPAR.


Serra-Guillen C.,Instituto Valenciano Of Oncologia | Llombart B.,Instituto Valenciano Of Oncologia | Sanmartin O.,Instituto Valenciano Of Oncologia
Actas Dermo-Sifiliograficas | Year: 2012

Dermatofibrosarcoma protuberans is the most common skin sarcoma, although its incidence is very low compared with other skin tumors. It presents as a slow-growing indurated plaque on which nodules develop over time. The lesion arises in the dermis but can invade subcutaneous tissue, fascia, muscle and even bone. COL1A1-PDGFB translocation is specific to dermatofibrosarcoma protuberans, and the presence of this fusion contributes to diagnosis in certain cases. A review of the literature provides evidence that recurrence is much lower after Mohs micorgraphic surgery than after conventional wide local excision. In the case of metastatic disease or when surgery would be mutilating, another recently approved treatment is the tyrosine kinase inhibitor imatinib. © 2011 Elsevier España, S.L. and AEDV. All rights reserved.


A number of molecular alterations have been described for melanoma. Melanomas with BRAF mutations tend to be located in areas of intermittent sun exposure, whereas melanomas with KIT mutations mostly appear in acral areas, the mucosas, and areas of chronic sun exposure. Sorafenib, a BRAF inhibitor, has a cytostatic effect on most melanomas with mutations affecting the mitogen-activated protein kinase (MAPK) pathway, and is also capable of triggering apoptosis in a small subgroup of these melanomas. By inhibiting KIT, imatinib has a cytostatic and cytotoxic effect on melanomas with KIT mutations, and probably has the same effect on another subgroup of melanomas with other as yet imperfectly understood KIT mutations. For therapy to be effective, agents should be selected according to the pathways associated with the genetic mutations present in the melanoma.

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