Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation. / Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento.

INTRODUCTION: The incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. METHODS: REGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. RESULTS: A total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. CONCLUSIONS: The distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First? / Inmunoterapia vs. terapia diana en el paciente con melanoma avanzado y mutación BRAF V600, ¿por cuál comenzar?

Systemic treatment with immunotherapy or targeted therapy can significantly improve survival in patients with advanced (metastatic or high-risk) melanoma. Fifty percent of patients with melanoma have a BRAF mutation. Decisions on optimal sequencing of systemic treatments should take into account drug- and tumor-related factors and patient characteristics. Although the combination of ipilimumab and nivolumab is associated with the best survival outcomes, it is associated with significant toxicity. Targeted therapy may be a more favorable option in certain clinical situations. We review the literature on immunotherapy and targeted therapy in melanoma and present an algorithm for guiding decision-making on their use as first-line systemic treatments for advanced BRAF-mutated melanoma.

Resistance to apoptosis in complicated Crohn's disease: Relevance in ileal fibrosis.

BACKGROUND AND AIMS: The stiffening of the extracellular matrix, and changes in its cellular and molecular composition, have been reported in the pathogenesis of fibrosis. We analyze the mechanisms that perpetuate ileal fibrosis in surgical resections of complicated Crohn's disease patients. METHODS: Ileal resections were obtained from affected and non-affected tissue of stenotic or penetrating Crohn's disease behavior. Ilea from non-IBD patients were used as control tissue. All samples underwent RNA sequencing. Human small intestinal fibroblasts were treated for 48 h with IL-1ß, TFGß1, PDGFB or TNF-α. Resistance to apoptosis was analysed by RT-PCR, western blot and immunohistochemistry in ileal tissue and by RT-PCR and FACS in cultured cells. RESULTS: Growth factor-driven signaling pathways and increased RAS GTPase activity were up-regulated in affected ilea in which we found expression of both the antiapoptotic molecule MCL1 and the transcription factor ETS1 in submucosal fibroblasts, and a senescence-associated secretory phenotype. In cultured intestinal fibroblasts, PDGFB induced an ETS1-mediated resistance to apoptosis that was associated with the induction of both of TGFB1 and IL1B, a cytokine that replicated the expression of SASP detected in ileal tissue. ETS1 drove fibroblast polarization between inflammatory and fibrogenic phenotypes in IL1ß-treated cells. CONCLUSIONS: Our data show resistance to apoptosis in complicated ileal CD, and demonstrate that PDGFB induce an ETS1-mediated resistance to apoptosis associated with an inflammatory and fibrogenic pattern of expression in intestinal fibroblasts. Results point to PDGFRB, IL1R1 or MCL1 as potential targets against ileal fibrosis.

[Translated article] Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First?

Systemic treatment with immunotherapy or targeted therapy can significantly improve survival in patients with advanced (metastatic or high-risk) melanoma. Fifty percent of patients with melanoma have a BRAF mutation. Decisions on optimal sequencing of systemic treatments should take into account drug- and tumor-related factors and patient characteristics. Although the combination of ipilimumab and nivolumab is associated with the best survival outcomes, it is associated with significant toxicity. Targeted therapy may be a more favorable option in certain clinical situations. We review the literature on immunotherapy and targeted therapy in melanoma and present an algorithm for guiding decision-making on their use as first-line systemic treatments for advanced BRAF-mutated melanoma.

Selection of Quality Indicators for the Certification of Dermato-Oncology Units: The CUDERMA Project Delphi Consensus Study. / Proyecto CUDERMA: Consenso Delphi de los indicadores de calidad para la certificación de las unidades de dermatología de atención en dermato-oncología.

Quality indicators are crucial for standardizing and guaranteeing the quality of health care practices. The Spanish Academy of Dermatology and Venereology (AEDV) launched the CUDERMA Project to define quality indicators for the certification of specialized units in dermatology; the first 2areas selected were psoriasis and dermato-oncology. The aim of this study was to achieve consensus on what should be evaluated by these indicators using a structured process comprising a literature review and selection of an initial list of indicators to be evaluated in a Delphi consensus study following review by a multidisciplinary group of experts. The selected indicators were evaluated by a panel of 28 dermatologists and classified as either «essential¼ or «of excellence¼. The panel agreed on 84 indicators, which will be standardized and used to develop the certification standard for dermato-oncology units.

Teledermatology-driven topical therapy of actinic keratosis: a comparative study of clinical effectiveness and compliance.

BACKGROUND: Teledermatology (TD) provides efficient care for skin cancer patients. OBJECTIVE: To compare the clinical effectiveness of imiquimod 5% for the treatment of AK with in-person care and through TD. METHODS: Longitudinal prospective controlled study including patients with single AK diagnosed and treated at face-to-face visits (FTF group) or through teledermatology (TD group) with imiquimod 5% cream. The main outcome measures assessed were the complete and global response percentage (CR and GR) under per-protocol (PP) and intention-to-treat (ITT) analysis. RESULTS: A total of 157 patients were enrolled (FTF = 75, TD = 82). PP analysis showed CR in 66.7% of FTF patients and 65.6% in TD patients (P > 0.05). The ITT yielded CR in 64.0% and 51.2% in FTF visits and TD, respectively (P = 0.073). The analysis showed an advantage of FTF care against TD in achieving GR (84.0% vs. 70.7%; P = 0.036). Facial location and local adverse reactions were the only explanatory factors of complete response in the ITT approach. Treatment completion was found in 90.7% and 72.0% in the FTF and TD groups, respectively (P = 0.004). CONCLUSIONS: Improvements in patient counselling at the primary care centre are needed before the implementation of TD as a routine methodology for the management of AK.

Practice Models in Teledermatology in Spain: Longitudinal Study, 2009-2014. / Modelos de práctica de la teledermatología en España. Estudio longitudinal 2009-2014.

INTRODUCTION: Teledermatology is the most advanced clinical specialty in telemedicine. The development of teledermatology in specific countries has not been studied in depth. METHODS: Our objective was to analyze teledermatology models in clinical practice in Spain. We paid special attention to organization, technical aspects, training, and the advantages/disadvantages as seen by teledermatologists. Two surveys were carried out (2009 and 2014). RESULTS: Teledermatology was used at 25 centers in 2009 and at 70 in 2014. The extended survey was completed by 21 centers in 2009 and 41 in 2014. Store-and-forward teledermatology was the main technique (83%) in 2014. Only 12% of centers used the real-time method, and 5% used a hybrid modality. Patients lived less than 25km away in 75% of cases (urban teledermatology). Most centers used mid-range bridge cameras; only 12% used mobile phones. Teledermoscopy and tertiary teledermatology were each used in 15% of centers. Teledermatology was restricted to skin cancer in 25% of cases, and 66% of centers used it to train primary care physicians. The main advantages, assessed on a scale of 1 to 10, were prioritization in cancer screening (8.3), rapid emergency care (7.8), training of and communication with primary care physicians (7.6), screening for trivial conditions (7.6), and reduction in the number of face-to-face visits (7.6). The main disadvantages were poor image quality (6.3), fear of error (5.7), difficulty in coordinating with primary care physicians (3.8), and time commitment (3.3). Between 2009 and 2014, the number of centers using teledermatology and the number of teledermatologists increased, as did use of the store-and-forward and urban models. The technology used also improved. CONCLUSION: Teledermatology is an emerging technology that is becoming well established in Spain. More than 25% of dermatology centers in Spain have implemented a teledermatology model. Store-and-forward in an urban setting is the most widely used modality. Teledermatologists see this technology as an effective option with more advantages than disadvantages. General satisfaction is high, although there is room for significant improvement in some areas.

Lymph Node Dissection in Patients With Melanoma and Sentinel Lymph Node Metastasis: An Updated, Evidence-Based Decision Algorithm. / Disección ganglionar en el paciente con melanoma y metástasis en el ganglio centinela: propuesta de decisión basada en la evidencia actual.

Recent publication of the results of clinical trials in which lymph node dissection was not associated with any survival benefit in patients with sentinel node metastasis makes it necessary to reconsider the treatment of patients with melanoma. This article provides an update on the available evidence on the diverse factors (routes of metastatic spread, predictors, adjuvant therapy, etc.) that must be considered when treating patients with sentinel node-positive melanoma. The authors propose a decision-making algorithm for use in this clinical setting. The current evidence no longer supports lymph node dissection in patients with low-risk sentinel node metastasis (sentinel node tumor load ≤1mm).

Reliability of the MDi Psoriasis® Application to Aid Therapeutic Decision-Making in Psoriasis. / Fiabilidad de una aplicación de ayuda a la toma de decisiones terapéuticas en el paciente con psoriasis (MDi Psoriasis®).

BACKGROUND: Therapeutic decisions in psoriasis are influenced by disease factors (e.g., severity or location), comorbidity, and demographic and clinical features. OBJECTIVE: We aimed to assess the reliability of a mobile telephone application (MDi-Psoriasis) designed to help the dermatologist make decisions on how to treat patients with moderate to severe psoriasis. METHOD: We analyzed interobserver agreement between the advice given by an expert panel and the recommendations of the MDi-Psoriasis application in 10 complex cases of moderate to severe psoriasis. The experts were asked their opinion on which treatments were most appropriate, possible, or inappropriate. Data from the same 10 cases were entered into the MDi-Psoriasis application. Agreement was analyzed in 3 ways: paired interobserver concordance (Cohen's κ), multiple interobserver concordance (Fleiss's κ), and percent agreement between recommendations. RESULTS: The mean percent agreement between the total of 1210 observations was 51.3% (95% CI, 48.5-54.1%). Cohen's κ statistic was 0.29 and Fleiss's κ was 0.28. Mean agreement between pairs of human observers only, excluding the MDi-Psoriasis recommendations, was 50.5% (95% CI, 47.6-53.5%). Paired agreement between the recommendations of the MDi-Psoriasis tool and the majority opinion of the expert panel (Cohen's κ) was 0.44 (68.2% agreement). CONCLUSIONS: The MDi-Psoriasis tool can generate recommendations that are comparable to those of experts in psoriasis.

Methotrexate in Moderate to Severe Psoriasis: Review of the Literature and Expert Recommendations.

Methotrexate (MTX) is the most frequently used conventional systemic drug in the treatment of psoriasis. Despite over 50years of experience in this setting, certain aspects of the use of this drug in clinical practice are still little standardized and poorly understood. For this reason, a group of 15 experts took part in a consensus development conference to achieve consensus on a series of recommendations on the use of MTX in psoriasis. The guidelines, which were developed on the basis of a systematic review of the literature, were validated by 2 rounds of voting and categorized by level of evidence and grade of recommendation. Before MTX can be used to treat moderate to severe psoriasis, the patient must be evaluated to assess the suitability of the treatment, including consideration of vaccination status and screening for tuberculosis and pregnancy. The recommended starting dose for a patient with no risk factors is 10 to 20mg/wk, the therapeutic dose for most patients is 15mg/wk, and the maximum dose is 20mg/wk. Most patients who respond to treatment will show improvement within 8weeks. Parenteral administration of MTX is desirable when there is a risk of erroroneous dosing, nonadherence, gastrointestinal intolerance, or inadequate response to the therapeutic dose taken orally. Noninvasive methods are preferred for monitoring hepatotoxicity. MTX is a good treatment option for patients with a history of cancer, but is not recommended in patients with chronic hepatitisB infection or individuals who are seropositive for human immunodeficiency virus.

Yield of Computed Tomography at Baseline Staging of Melanoma.

BACKGROUND: Current guidelines call for baseline imaging only for very high-risk (T4b) primary cutaneous melanomas. OBJECTIVES: To estimate the frequency of computed tomography (CT) at baseline staging of primary cutaneous melanoma and the diagnostic yield of CT; and to describe the types and frequencies of incidentaloma findings. MATERIAL AND METHODS: Cross-sectional study of cutaneous melanoma cases (tumor classifications Tis to T4bN0M0) attended between 2008 and 2014 in a specialized melanoma unit. Reports of CT scans performed during baseline staging were reviewed to determine the frequency of positive scan results, incidentaloma findings, unit cost for detection of metastasis, and factors associated with the decision to order CT. RESULTS: CT results were available for 310 of the 419 patients included (73.99%). The tumor classifications were as follows: Tis, 17; T1, 137; T2, 71; T3, 48; and T4, 37. The CT results were negative in 81.61%, and incidentalomas were found in 18.06%. Additional primary tumors were found in 2 patients (0.64%), and metastasis was identified in one patient (0.32%). The cost of finding the case of metastasis was €71,234.90. A T2 tumor classification (odds ratio [OR], 8.73) and age under 70 years (OR, 3.53) were associated with greater likelihood of CT being ordered. Excision of the primary tumor in the melanoma unit (OR, 0.08) was associated with less likelihood of ordering CT. CONCLUSIONS: The results for this patient series support current recommendations restricting CT at baseline to cases where there is high risk of metastasis (stagesiiC-iii).