Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study. / [Artículo traducido] Sonidegib para el tratamiento del carcinoma basocelular avanzado en práctica clínica real: estudio nacional multicéntrico.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24 h and 48 h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study.

BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. OBJECTIVE: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile. METHODS: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected. RESULTS: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24h and 48h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. CONCLUSION: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.

Clinical Practice Guideline on Melanoma From the Spanish Academy of Dermatology and Venereology (AEDV). / Guía de práctica clínica de melanoma de la Academia Española de Dermatología y Venereología.

Specialist approaches to the diagnosis and treatment of melanoma have undergone many changes. This guideline aims to provide Spanish dermatologists with evidence-based information for resolving the most common doubts that arise in clinical practice. Members of the Spanish Oncologic Dermatology and Surgery Group (GEDOC) with experience treating melanoma were invited to participate in drafting the guideline. The group developed a new guideline on the basis of existing ones, using the ADAPTE collaboration process, first summarizing the care process and posing relevant clinical questions, then selecting guidelines with the best scores according to the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. Finally, the group searched the selected guidelines for answers to the clinical questions, drafted recommendations, and sent them for external review. The guideline is structured around 21 clinical questions chosen for their relevance to issues that make clinical decisions about the management of melanoma difficult. Evidence from existing guidelines was used to answer the questions. A limitation of this guide derives from the scarce evidence available for answering some questions. Moreover, some areas are changing rapidly, so recommendations must be updated often. The present guideline offers answers to clinical questions about the routine management of melanoma in clinical practice and provides dermatologists with a reference to guide decisions, taking into consideration the resources available and patient preferences.

Diagnosis and Treatment of Basal Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline. / Carcinoma basocelular cutáneo: diagnóstico y tratamiento en atención especializada dermatológica. Guía de Práctica Clínica de la AEDV.

BACKGROUND AND OBJECTIVE: Basal cell carcinoma (BCC) is the most common skin cancer in the general population. BCC is managed in a variety of ways, and available international guidelines are difficult to put into practice in Spain. This guideline aims to improve the management of BCC based on current evidence and provide a point of reference for Spanish dermatologists. MATERIAL AND METHODS: Members of the Spanish Oncologic Dermatology and Surgery Group (GEDOC) with experience treating BCC were invited to participate in drafting this guideline. The drafters used the ADAPTE collaboration process to develop the new guideline based on existing ones, first summarizing the care pathway and posing relevant clinical questions. They then searched for guidelines, assessed them with the AGREEII (Appraisal of Guidelines for Research and Evaluation) tool, and searched the selected guidelines for answers to the clinical questions. Finally, the recommendations were drafted and submitted for external review. RESULTS: The highest-scoring guidelines were from the Association of Dermatologists, the National Comprehensive Cancer Network, the European Dermatology Forum, and the European Academy of Dermatology and Venereology. A total of 11 clinical questions were answered. CONCLUSIONS: This new guideline answers the working group's clinical questions about the routine management of BCC in Spain. It provides dermatologists with a tool they can use for decision-making while taking into consideration the resources available and patient preferences.

Diagnosis and Treatment of Merkel Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline of the Spanish Academy of Dermatology and Venereology. / Carcinoma de células de Merkel: diagnóstico y tratamiento en atención especializada dermatológica. Guía de práctica clínica de la Academia Española de Dermatología y Venerología.

BACKGROUND AND OBJECTIVE: Merkel cell carcinoma is a rare, aggressive skin cancer that is managed in a great variety of ways. However, international clinical practice guidelines give only partial coverage to issues considered major problems.The recommendations presented here aim to provide Spanish dermatologists with a guide to improving disputed aspects of diagnosis, staging, and treatment of localized Merkel cell carcinomas. MATERIAL AND METHODS: The ADAPTE process was used. Members of the Spanish Group of Oncologic Dermatology and Surgery (GEDOC) with experience in treating Merkel cell carcinoma and interest in drafting these guidelines were selected. The group described the care process and listed the most important clinical questions. They then searched for guidelines and assessed them with the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. After consulting the guidelines for answers to their clinical questions, the group drafted the present statementand sent it for external review. RESULTS: The guidelines that scored highest in the AGREE II assessment step were the consensus-based interdisciplinary guideline of the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer, and those of the Comprehensive Cancer Network, the Alberta Health Services in Canada, the American Cancer Society, and the Cutaneous Oncology Group of the French Society of Dermatology. A total of 9 clinical questions were answered based on these guidelines. CONCLUSIONS: The guidelines presented here answer clinical questions that arise in routine practice. They can provide dermatologists with a starting point for decision-making, although available resources and patient preferences must always be borne in mind.

Evaluation of Structure Indicators for Assessing Skin Cancer Quality of Care in Dermatology Departments. / Evaluación de indicadores de estructura en la atención al paciente con cáncer de piel en los servicios de dermatología.

INTRODUCTION AND OBJECTIVES: A series of quality indicators for melanoma and nonmelanoma skin cancer were recently approved within a project promoted by the Healthy Skin Foundation of the Spanish AEDV. The aim of this study was to evaluate adherence to these indicators. MATERIAL AND METHODS: In November 2016, an anonymous questionnaire consisting of 32 items was sent to the heads of Spanish dermatology and venereology departments listed in the AEDV's database. The questions referred to the above-mentioned quality of care indicators. RESULTS: The questionnaire was completed by 104 of the 150 people contacted (response rate, 69.3%). The lowest response rate for any given question was 56% (84 respondents). Over 85% of respondents answered 29 questions or more (91%). The most widely used indicators were those related to the use of computed tomography or magnetic resonance imaging for squamous cell carcinoma (98%), followed by the availability of a standardized melanoma pathology report (90%). The least widely used indicators were related to availability of electrochemotherapy (25%) and other invasive therapies for locoregionally advanced melanoma (20%). CONCLUSIONS: Adherence to quality of cancer care criteria at the different hospitals evaluated varied. Our findings could be useful for identifying areas for improvement at different hospitals. Future studies should focus on measuring both process and outcome indicators.

Dynamic skin changes of acute radiation dermatitis revealed by in vivo reflectance confocal microscopy.

BACKGROUND: A better knowledge of the dynamic biological changes that the skin undergoes in response to ionizing radiation is advisable to improve the management of radiation dermatitis, allowing selection of patients needing treatment or close monitoring. OBJECTIVE: To describe the evolution of the skin in response to ionizing radiation through the reflectance confocal microscopy (RCM) features of acute radiation dermatitis. METHODS: In this prospective descriptive study, six women (median age, 55 years; range, 45-80 years) diagnosed with breast cancer in stages IA-IB undergoing adjuvant radiotherapy were included in the study through consecutive sampling. Clinical, dermoscopic and RCM evaluation of the skin were performed prior to treatment and on days 1, 15, 30 and 45 after radiotherapy. RESULTS: While clinical features of radiation dermatitis emerged after 30 days on average, histopathological changes were detectable by RCM after a mean time of 15 days. The main RCM features included initial appearance of spongiosis, exocytosis and inflammatory cells followed by the presence of dendritic-shaped cells, 'streaming-like figures', 'broken geographic papillae', epidermal architectural disarray, effacement of rete ridges, melanophages and, finally, hyperpigmentation of the basal layer. CONCLUSIONS: RCM may safely detect the dynamic biological changes that the skin undergoes in response to ionizing radiation, even before than clinical onset of acute radiation dermatitis. Therefore, RCM may be useful to make an early and non-invasive diagnosis of radiation dermatitis during radiotherapy, allowing an early selection of patients needing treatment or close monitoring and avoiding skin biopsies.

[Sentinel lymph node in nonmelanoma skin cancer]. / Ganglio centinela en cáncer de piel no melanoma.

Sentinel lymph node biopsy is performed routinely in melanoma because lymph node progression has been shown to be the strongest predictor of survival. Given the proven relevance of biopsy findings in this type of skin cancer, the procedure has been extended to other skin tumors. Experience in nonmelanoma cancer is much more limited and the prognostic usefulness of biopsy results remains to be shown. This critical review of the literature on the various skin tumors in which sentinal node biopsy has been practiced discusses the usefulness of this procedure.

[Store-and-forward teledermatology: assessment of validity in a series of 2000 observations]. / Teledermatología diferida: análisis de validez en una serie de 2.000 observaciones.

BACKGROUND AND OBJECTIVES: The aim of this study was to assess the validity of store-and-forward teledermatology as a tool to support physicians in primary care and hospital emergency services and reduce the requirement for face-to-face appointments. Diagnostic validity and the approach chosen for patient management (face-to-face vs teledermatology) were compared according to patient origin and diagnostic group. MATERIAL AND METHODS: Digital images from 100 patients were assessed by 20 different dermatologists and the diagnoses offered were compared with those provided in face-to-face appointments (gold standard). The proposed management of the different groups of patients was also compared. RESULTS: The percentage complete agreement was 69.05% (95% confidence interval [CI], 66.9%-71.0%). The aggregate agreement was 87.80% (95% CI, 86.1%-89.0%). When questioned about appropriate management of the patients, observers elected face-to-face consultation in 60% of patients (95% CI, 58%-61%) and teledermatology in 40% (95% CI, 38%-41%). Diagnostic validity was higher in patients from primary care (76.1% complete agreement and 91.8% aggregate agreement) than those from hospital emergency services (61.8% complete agreement, 83.4% aggregate agreement) (p < 0.001) and teledermatology was also chosen more often in patients from primary care compared with those from emergency services (42% vs 38%; p=0.003). In terms of diagnostic group, higher validity was observed for patients with infectious diseases (73.3% complete agreement and 91.3% aggregate agreement) compared to those with inflammatory disease (70.8% complete agreement and 86.4% aggregate agreement) or tumors (63.0% complete agreement and 87.2% aggregate agreement) (p <0.001). Teledermatology was also chosen more often in patients with infectious diseases (52%) than in those with inflammatory disease (40%) or tumors (28%) (p <0.001). CONCLUSIONS: Store-and-forward teledermatology has a high level of diagnostic validity, particularly in those cases referred from primary care and in infectious diseases. It can be considered useful for the diagnosis and management of patients at a distance and would reduce the requirement for face-to-face consultation by 40%.

[Surgical vs nonsurgical treatment of basal cell carcinoma]. / Tratamiento quirúrgico vs. no quirúrgico en el carcinoma basocelular.

Numerous therapeutic options are now available for the treatment of basal cell carcinoma. However, few randomized controlled trials with 5-year follow-up have compared the effectiveness of the different treatments. Such a comparison is difficult, probably because efficacy depends on several factors: those related to the tumor, the patient, the technique, and the dermatologist's experience. We first describe the available therapeutic options, including certain innovative treatments. We have divided them into 2 main groups-surgical and nonsurgical-and focus on the indications, advantages, and disadvantages of each one, as well as on the cure and recurrence rates. Then, based on the evidence reviewed, we attempt to provide an outline of the therapeutic strategies recommended in basal cell carcinoma, and the approach to be used in specific situations. We also describe our own experience.

[Management of basal cell carcinomas with positive margins]. / Actitud ante los epiteliomas basocelulares con bordes afectos.

A common problem in day-to-day practice is the approach to take following resection of basal cell carcinoma with positive margins. In such cases, it is important to decide whether we should take a wait-and-see approach or consider re-excision or radiotherapy. To make this decision, 4 key points need to be clarified: the significance of positive margins; whether positive margins are equivalent to tumor persistence; whether negative margins equate with complete excision; and the rate of recurrence in cases of re-excision compared in those in which a wait and see approach is taken. Having addressed each of these points, the approach will depend on the characteristics of the individual case. Based on the evidence presented, an aggressive approach involving re-excision would seem indicated in aggressive cases, whereas a flexible strategy combining observation, surgery, and radiotherapy (or other treatments) can be used in less aggressive cases.

[Kaposi's sarcoma treated with topical alitretinoin]. / Sarcoma de Kaposi clásico tratado con alitretinoína tópica.

Kaposi's sarcoma is a multifocal neoplastic process with four clinical variants, all of them induced by human herpes virus 8. Currently there is no treatment of choice and it depends on the extension and location of the lesions as well as on the clinical type of the disease. Alitretinoin gel 0.1 % is approved for the treatment of cutaneous lesions of AIDS-associated Kaposi's sarcoma. The majority of its side effects appear at the site of application and can lead to therapy withdrawal. We report a case of Kaposi's sarcoma treated with topical alitretinoin that had a favourable evolution in spite of an intense local reaction.

Livedo reticularis associated with interferon alpha therapy in two melanoma patients.

We report two patients who developed intense livedo reticularis clearly related to the administration of interferon alpha 2b as an adjuvant therapy for melanoma. Histological studies showed scattered perivascular infiltrates without vasculitis. Laboratory tests excluded any underlying condition. Resolution of the symptoms was observed in both patients when interferon alpha was withdrawn. These cases highlight the occurrence of livedo reticularis as an uncommon side-effect of interferon alpha treatment.

Massive scrotal calcinosis.

BACKGROUND: Scrotal calcinosis is a benign entity characterized by the appearance of calcific masses within the dermis of scrotal skin. Its pathogenesis has not been fully elucidated. OBJECTIVE: A 36-year-old man with massive scrotal calcinosis is described. Our aim was to perform a histologic examination of the surgical piece with subsequent closure of the defect achieving satisfactory cosmetic results. METHODS: Case report and literature review. RESULTS: Histologic studies of multiple nodules showed no epithelial lining and one calcified epidermal cyst. Subtotal excision of the scrotal wall was performed with excellent results. CONCLUSION: Even though the pathogenic mechanism of this entity is still unclear, our findings support the theory of dystrophic calcification of epidermoid cysts. Surgical treatment is the only definitive treatment. Subtotal excision of the scrotal wall in cases of massive calcinosis may be performed with good results.

Recall phenomenon with the unusual presence of eccrine squamous syringometaplasia.

The recall phenomenon is an inflammatory reaction limited to a previously X-irradiated field when the patient is treated months or years later with certain drugs. Only a few cases have been reported in dermatological journals. We report a patient with lymphoma who was treated with low-dose abdominal irradiation and high-dose irradiation to the knees and who, 2 months later, when chemotherapy was started, developed a pronounced inflammatory reaction limited to the areas treated with high-dose irradiation. A skin biopsy specimen showed features of radiation damage, marked epidermal changes and extensive eccrine squamous syringometaplasia. This case of the recall phenomenon is of interest because we have found that there is apparently a radiation dose threshold for this event, and because this is the first report of its association with eccrine squamous syringometaplasia.