Association between several immune response-related genes and the effectiveness of biological treatments in patients with moderate-to-severe psoriasis.

Biological therapies are safer and more effective against psoriasis than conventional treatments. Even so, 30-50% of psoriatic patients show an inadequate response, which is associated with individual genetic heterogeneity. Pharmacogenetic studies have identified several single nucleotide polymorphisms (SNPs) as possible predictive and prognostic biomarkers for psoriasis treatment response. The objective of this study was to determine the link between several SNPs and the clinical response to biological therapies in patients with moderate-severe psoriasis. A set of 21 SNPs related to psoriasis and/or other immunological diseases were selected and analysed from salivary samples of patients (n = 88). Treatment effectiveness and patient improvement was assessed clinically through Relative Psoriasis Area and Severity Index (PASI), also called 'PASI response', as well as absolute PASI. Associations between SNPs and PASI factors were assessed at 3 and 12 months for every treatment category of IL-17, IL-23, IL-12&23 and TNF-α inhibitors. Multivariate correlation analysis and Fisher's exact test were used to analyse the relationship between SNPs and therapy outcomes. Several SNPs located in the TLR2, TLR5, TIRAP, HLA-C, IL12B, SLC12A8, TNFAIP3 and PGLYRP4 genes demonstrated association with increased short and long-term therapy-effectiveness rates. Most patients achieved values of PASI response ≥75 or absolute PASI<1, regardless of the biological treatment administered. In conclusion, we demonstrate a relationship between different SNPs and both short- and especially long-term effectiveness of biological treatment in terms of PASI. These polymorphisms may be used as predictive markers of treatment response in patients with moderate-to-severe psoriasis, providing personalized treatment.

Scalp Melanoma: A High-Risk Subset of Cutaneous Head and Neck Melanomas with Distinctive Clinicopathological Features.

Scalp melanomas (SM) have been previously associated with poor overall and melanoma-specific survival rates. The aim of this study was to describe and compare the clinicopathological characteristics and survival outcomes of SM and non-scalp cutaneous head and neck melanoma (CHNM). An observational multi-center retrospective study was designed based on patients with CHNM followed in two tertiary care hospitals. A hundred and fifty-two patients had CHNM, of which 35 (23%) had SM. In comparison with non-scalp CHNM, SM were more frequently superficial spreading and nodular subtypes, had a thicker Breslow index median (2.1 mm vs. 0.85 mm), and a higher tumor mitotic rate (3 vs. 1 mitosis/mm2) (p < 0.05). SM had a higher risk of recurrence and a higher risk of melanoma-specific death (p < 0.05). In the multivariate analysis, scalp location was the only prognostic factor for recurrence, and tumor mitotic rate was the only prognostic factor for melanoma-specific survival. We encourage routinely examining the scalp in all patients, especially those with chronic sun damage.

Multiple pilomatricomas in a child with xeroderma pigmentosum: Coincidence or association?

The association of multiple pilomatricomas with xeroderma pigmentosum has not been described. We report a case of a child with multiple pilomatricomas and photosensitivity who was found to have a pathogenic variant in exon 4 of XPA and a likely pathogenic variant in COL6A1.

Enfermedad de Crohn metastásica tratada con ustekinumab / Metastatic Crohn Disease Treated With Ustekinumab

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MicroRNAs expression associated with aggressive clinicopathological features and poor prognosis in primary cutaneous melanomas.

Several studies have focused on identifying microRNAs involved in the pathogenesis of melanoma. However, its association with clinicopathological features has been scarcely addressed. The aim of this study is to identify microRNAs expression profiles related to aggressive clinicopathological and molecular features, and to analyze the association with melanoma survival. A retrospective and observational study was performed in a series of 179 formalin-fixed paraffin embedded primary cutaneous melanomas. First, a screening analysis on a discovery set (n = 22) using miRNA gene chip array (Affymetrix, Santa Clara, California, USA) was performed. Differentially expressed microRNAs were detected employing the software Partek Genomic Suite. Validation of four microRNAs was subsequently performed in the entire series (n = 179) by quantitative real time PCR (qRT-PCR). MicroRNAs expression screening analysis identified 101 microRNAs differentially expressed according to Breslow thickness (≤1 mm vs. >1 mm), 79 according to the presence or absence of ulceration, 78 according to mitosis/mm2 (<1 mitosis vs. ≥1 mitosis) and 97 according to the TERT promoter status (wt vs. mutated). Six microRNAs (miR-138-5p, miR-130b-3p, miR-30b-5p, miR-34a-5p, miR-500a-5p, miR-339-5p) were selected for being validated by qRT-PCR in the discovery set (n = 22). Of those, miR-138-5p, miR-130b-3p, miR-30b-5p, miR-34a-5p were selected for further analysis in the entire series (n = 179). Overexpression of miR-138-5p and miR-130b-3p was significantly associated with greater Breslow thickness, ulceration, and mitosis. TERT mutated melanomas overexpressed miR-138-5p. Kaplan-Meier survival analysis showed poorer survival in melanomas with miR-130b-3p overexpression. Our findings provide support for the existence of a microRNA expression profile in melanomas with aggressive clinicopathological features and poor prognosis.

Two years results of electronic brachytherapy for basal cell carcinoma.

PURPOSE: The use of radiation therapy (RT) for non-melanoma skin cancer (NMSC) has been changing throughout the last century. Over the last decades, the use of radiotherapy has surged with the development of new techniques, applicators, and devices. In recent years, electronic brachytherapy (eBT) devices that use small x-ray sources have been introduced as alternative to radionuclide dependence. Nowadays, several devices have been incorporated, with a few series reported, and with a short follow-up, due to the recent introduction of these systems. The purpose of this work is to describe the clinical results of our series after two years follow-up with a specific eBT system. MATERIAL AND METHODS: This is a prospective single-center, non-randomized pilot study, to assess clinical results of electronic brachytherapy in basal cell carcinoma using the Esteya® system. In 2014, 40 patients with 60 lesions were treated. Patient follow-up on a regular basis was performed for a period of two years. RESULTS: Twenty-six patients with 44 lesions achieved two years follow-up. A complete response was documented in 95.5% of cases. Toxicity was mild (G1 or G2) in all cases, caused by erythema, erosion, or alopecia. Cosmesis was excellent in 88.6% of cases, and good in the rest. Change in pigmentation was the most frequent cosmetic alteration. CONCLUSIONS: This work is special, since the equipment's treatment voltage was 69.5 kV, and this is the first prospective study with long term follow-up with Esteya®. These preliminary report show excellent results with less toxicity and excellent cosmesis. While surgery has been the treatment of choice, certain patients might benefit from eBT treatment. These are elderly patients with comorbidities or undergoing anticoagulant treatment as well as those who simply refuse surgery or might have other contraindications.

Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel.

Molecular diagnostics are increasingly performed routinely in the diagnosis and management of patients with melanoma due to the development of novel therapies that target specific genetic mutations. The development of next-generation sequencing (NGS) technologies has enabled to sequence multiple cancer-driving genes in a single assay, with improved sensitivity in mutation detection. The main objective of this study was the design and implementation of a melanoma-specific sequencing panel, and the identification of the spectrum of somatic mutations in a series of primary melanoma samples. A custom panel was designed to cover the coding regions of 35 melanoma-related genes. Panel average coverage was 2,575.5 reads per amplicon, with 92,8% of targeted bases covered ≥500×. Deep coverage enabled sensitive discovery of mutations in as low as 0.5% mutant allele frequency. Eighty-five percent (85/100) of the melanomas had at least one somatic mutation. The most prevalent mutated genes were BRAF (50%;50/199), NRAS (15%;15/100), PREX2 (14%;14/100), GRIN2A (13%;13/100), and ERBB4 (12%;12/100). Turn-around-time and costs for NGS-based analysis was reduced in comparison to conventional molecular approaches. The results of this study demonstrate the cost-effectiveness and feasibility of a custom-designed targeted NGS panel, and suggest the implementation of targeted NGS into daily routine practice.

Electronic brachytherapy for superficial and nodular basal cell carcinoma: a report of two prospective pilot trials using different doses.

PURPOSE: Basal cell carcinoma (BCC) is a very common cancer in the Caucasian population. Treatment aims to eradicate the tumor with the lowest possible functional and aesthetic impact. Electronic brachytherapy (EBT) is a treatment technique currently emerging. This study aims to show the outcomes of two consecutive prospective pilot clinical trials using different radiation doses of EBT with Esteya(®) EB system for the treatment of superficial and nodular basal cell carcinoma. MATERIAL AND METHODS: Two prospective, single-center, non-randomized, pilot studies were conducted. Twenty patients were treated in each study with different doses. The first group (1) was treated with 36.6 Gy in 6 fractions of 6.1 Gy, and the second group (2) with 42 Gy in 6 fractions of 7 Gy. Cure rate, acute toxicity, and late toxicity related to cosmesis were analyzed in the two treatment groups. RESULTS: In group 1, a complete response in 90% of cases was observed at the first year of follow-up, whereas in group 2, the complete response was 95%. The differences with reference to acute toxicity and the cosmetic results between the two treatment groups were not statistically significant. CONCLUSIONS: Our initial experience with Esteya(®) EB system to treat superficial and nodular BCC shows that a dose of 36.6 Gy and 42 Gy delivered in 6 fraction of 7 Gy achieves a 90% and 95% clinical cure rate at 1 year, respectively. Both groups had a tolerable toxicity and a very good cosmesis. The role of EBT in the treatment of BCC is still to be defined. It will probably become an established option for selected patients in the near future.

Efficacy and safety of electronic brachytherapy for superficial and nodular basal cell carcinoma.

PURPOSE: Surface electronic brachytherapy (EBT) is an alternative radiotherapy solution to external beam electron radiotherapy and high-dose-rate radionuclide-based brachytherapy. In fact, it is also an alternative solution to surgery for a subgroup of patients. The objective of this work is to confirm the clinical efficacy, toxicity and cosmesis of a new EBT system, namely Esteya(®) in the treatment of nodular and superficial basal cell carcinoma (BCC). MATERIAL AND METHODS: This is a prospective single-center, non-randomized pilot study to assess the efficacy and safety of EBT in nodular and superficial BCC using the Esteya(®) system. The study was conducted from June 2014 to February 2015. The follow up time was 6 months for all cases. RESULTS: Twenty patients with 23 lesions were included. A complete response was documented in all lesions (100%). A low level of toxicity was observed after the 4(th) fraction in all cases. Erythema was the most frequent adverse event. Cosmesis was excellent, with more than 60% of cases without skin alteration and with subtle changes in the rest. CONCLUSIONS: Electronic brachytherapy with Esteya(®) appears to be an effective, simple, safe, and comfortable treatment for nodular and superficial BCC associated with excellent cosmesis. It could be a good choice for elderly patients, patients with contraindications for surgery (due to comorbidities or anticoagulant drugs) or patients where surgery would result in a more disfiguring outcome. A longer follow-up and more studies are needed to confirm these preliminary results.

Depth determination of skin cancers treated with superficial brachytherapy: ultrasound vs. histopathology.

PURPOSE: The purpose of this study is to compare high frequency ultrasonography (HFUS) and histpathologic assessment done by punch biopsy in order to determine depth of basal cell carcinoma (BCC), in both superficial and nodular BCCs prior to brachytherapy treatment. MATERIAL AND METHODS: This study includes 20 patients with 10 superficial and 10 nodular BCCs. First, punch biopsy was done to confirm the diagnosis and to measure tumour depth (Breslow rate). Subsequently, HFUS was done to measure tumour depth to search for correlation of these two techniques. RESULTS: Neither clear tendency nor significance of the punch biopsy vs. HFUS depth determination is observed. Depth value differences with both modalities resulted patient dependent and then consequence of its uncertainty. Conceptually, HFUS should determine the macroscopic lesion (gross tumour volume - GTV), while punch biopsy is able to detect the microscopic extension (clinical target volume - CTV). Uncertainties of HFUS are difficult to address, while punch biopsy is done just on a small lesion section, not necessarily the deepest one. CONCLUSIONS: According to the results, HFUS is less accurate at very shallow depths. Nodular cases present higher depth determination differences than superficial ones. In our clinical practice, we decided to prescribe at 3 mm depth when HFUS measurements give depth lesion values smaller than this value.

Clinical implementation of a new electronic brachytherapy system for skin brachytherapy.

Although surgery is usually the first-line treatment for nonmelanoma skin cancers, radiotherapy (RT) may be indicated in selected cases. Radiation therapy as primary therapy can result in excellent control rates, cosmetics, and quality of life. Brachytherapy is a radiation treatment modality that offers the most conformal option to patients. A new modality for skin brachytherapy is electronic brachytherapy. This involves the placement of a high dose rate X-ray source directly in a skin applicator close to the skin surface, and therefore combines the benefits of brachytherapy with those of low energy X-ray radiotherapy. The Esteya electronic brachytherapy system is specifically designed for skin surface brachytherapy procedures. The purpose of this manuscript is to describe the clinical implementation of the new Esteya electronic brachytherapy system, which may provide guidance for users of this system. The information covered includes patient selection, treatment planning (depth evaluation and margin determination), patient marking, and setup. The justification for the hypofractionated regimen is described and compared with others protocols in the literature. Quality assurance (QA) aspects including daily testing are also included. We emphasize that these are guidelines, and clinical judgment and experience must always prevail in the care of patients, as with any medical treatment. We conclude that clinical implementation of the Esteya brachytherapy system is simple for patients and providers, and should allow for precise and safe treatment of nonmelanoma skin cancers.

Lipomatosis benigna simétrica; síndrome de Madelung / Symmetric benign lipomatosis; Madelung syndrome

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Tratamiento de la psoriasis con fármacos anti-TNF- en pacientes con infección por el virus de la inmunodeficiencia humana / Treatment of psoriasis with anti-TNF drugs in human immunodeficiency virus-infected patients

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