New patents on topical anesthetics.

Anesthesia is defined as a total or partial loss of sensation and it may be general, local or topical, depending on the method of drug administration and area of the body affected. General anesthesia is a reversible state of unconsciousness produced by anesthetic agents, characterized by amnesia, muscle relaxation and loss of sensitivity to pain of the whole body. General anesthetic drugs can be classified into two main groups according to their predominant molecular pharmacological effects: volatile and intravenous agents. Local anesthesia produce a reversible loss of sensation in a portion of the body and it reversibly block impulse conduction along nerve axons and other excitable membrane. All local anesthetics (LA) are membrane stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes. They act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The main local anesthetic (LA) agents for skin anesthesia are benzocaine (aminoester), prilocaine and lidocaine (aminoamides) which are commercially available as gels, ointments and creams (benzocaine and eutectic mixture of lidocaine and prilocaine) or as a bioadhesive (lidocaine) with different compositions (vehicles and excipients) for adults or pediatric use. Topical anesthetics decrease anxiety, pain and discomfort during cutaneous procedures and provide effective analgesia with rapid onset, prolonged duration and minimal side effects. This article outlines the different classes of topical anesthetics available and gives an overview of the mechanism of action, metabolism of each different class, of the possible complications that can occur because of their use and their possible treatment options and new patents. © 2014 Bentham Science Publishers

Case Report: Cetuximab use in advanced cutaneous squamous cell carcinoma resistant to chemotherapy

We present the case of a 60-year-old man with unresectable cutaneous squamous cell carcinoma (cSCC) of the sternal area, which was not amenable to radiation therapy. The treatment history of this patient is remarkable as the disease had progressed through all lines of conventional therapy established in the literature. We decided to initiate treatment with epidermal growth factor receptor (EGFR) inhibitor cetuximab and we reassessed the patient after 12 weeks with a whole-body CT scan, documenting stability in the size and radiologic features of the disease. Cetuximab, like all current treatments for advanced cSCC, is administered off-label and proved effective in preventing further progression of disease in our patient

Agminated Blue Nevus: Two Case Reports and a Mini-review of the Literature

Agminated blue nevus (ABN) is a melanocytic nevus rarely mentioned in the literature and not well known. The term agminated is used when many blue nevi are clustered together in a sharply demarcated area ≤10 cm. Specific dermatoscopic features have not currently been clearly defined. We describe two cases of ABN and provide a review of the literature, reporting the main points in order to facilitate the diagnosis of this rare entity.  </p

Peripheral blood regulatory T cell measurements correlate with serum vitamin D level in patients with psoriasis

OBJECTIVE:Vitamin D is the precursor of a hormone (1,25-dihydroxyvitamin D3), which has many biological effects in the skin. The immune modulator properties of vitamin D are mediated in part through effects on regulatory T cells (T-reg). Currently, in psoriasis, the relationship between vitamin D and T-reg has not well elucidated. We assess whether vitamin D status is correlated with circulating T-reg in patients affected by psoriasis and if there is a correlation with the severity of the disease evaluated with Psoriasis Area Severity Index (PASI) score. PATIENTS AND METHODS:For each patient we have analyzed, PASI-score, serum levels vitamin D and regulatory T cell percentages. Spearmen's coefficient was used between serum vitamin D levels and the predictors. Subsequently, the independent predictive factors were assessed by Multiple Regression. RESULTS:A total of 26 patients were included in our analysis. Using no parametric Spearman's Coefficient test between serum levels of vitamin D and the single variables, we found an association with T-reg population (p &lt; 0.001) and with PASI-score (p = 0.04). CONCLUSIONS:While vitamin D treatment induces a cytokine profile known to favor the differentiation of T cells with suppressive activity, at the same time, several studies showed how vitamin D can prime for tolerogenic dendritic cells able to favor the differentiation of Treg from T naïve cells. Low levels of vitamin-D may decrease the number of circulatory T-reg, disrupting the immunological homeostasis in psoriatic patients and encouraging the inflammatory activity

Paraneoplastic pemphigus. A trait d’union between dermatology and oncology

Paraneoplastic pemphigus is a rare autoimmune disease of the skin associated with neoplasm. Nowadays, the pathogenesis of paraneoplastic pemphigus is not fully understood. Due to its rarity, various criteria have been proposed for the diagnosis. For this reason, several diagnostic methods have been considered useful for the diagnosis of paraneoplastic pemphigus including indirect immunofluorescence, direct immune of fluorescence, immunoprecipitation,immunoblotting, and enzyme-linked immunosorbent assay (ELISA). However, the polymorphic clinical features and the various results of laboratory tests and pathological evaluation present a challenge for the clinician

MiRNAs as Potential Prognostic Biomarkers for Metastasis in Thin and Thick Primary Cutaneous Melanomas.

Background/Aim: The identification of novel prognostic biomarkers for melanoma metastasis is essential to improve patient outcomes. To this aim, we characterized miRNA expression profiles in relation to metastasis in melanoma and correlated miRNAs expression with clinicalpathological factors. Materials and Methods: MiR-145-5p, miR-150-5p, miR-182-5p, miR-203-3p, miR-205-5p and miR211-5p expression levels were analyzed in primary cutaneous melanomas, including thin and thick melanomas, and in melanoma metastases by quantitative Real-Time PCR. Results: A significantly lower miR-205-5p expression was found in metastases compared to primary melanomas. Furthermore, a progressive down-regulation of miR-205-5p expression was observed from loco-regional to distant metastasis. Significantly lower miR-145-5p and miR-203-3p expression levels were found in cases with Breslow thickness &gt;1 mm, high Clark level, ulceration and mitotic rate ≥1/mm2. Conclusion: Our findings point to miR-205-5p as potential biomarker of distant metastases and to miR-145-5p and miR-203-3p as markers of aggressiveness in melanoma

Metastases risk in thin cutaneous melanoma: Prognostic value of clinical-pathologic characteristics and mutation profile

Background: A high percentage of patients with thin melanoma (TM), defined as lesions with Breslow thickness ≤1 mm, presents excellent long-term survival, however, some patients develop metastases. Existing prognostic factors cannot reliably differentiate TM patients at risk for metastases. Objective: We aimed at characterizing the clinical-pathologic and mutation profile of metastatic and not-metastatic TM in order to distinguish lesions at risk of metastases. Methods: Clinical-pathologic characteristics were recorded for the TM cases analyzed. We used a Next Generation Sequencing (NGS) multi-gene panel to characterize TM for multiple somatic mutations. Results: A statistically significant association emerged between the presence of metastases and Breslow thickness ≥0.6 mm (p=0.003). None of TM with lymph-node involvement had Breslow thickness < 0.6 mm. Somatic mutations were identified in 19 of 21 TM analyzed (90.5%). No mutations were observed in two not-metastatic cases with the lowest Breslow thickness (≤0.4 mm), whereas mutations in more than one gene were detected in one metastatic case with the highest Breslow thickness (1.00 mm). Conclusion: Our study indicates Breslow thickness ≥0.6 mm as a valid prognostic factor to distinguish TM at risk for metastases

Clinicopathological predictive factors of melanoma lung metastases

Background: The lung is the second most common site for metastatic malignant melanoma, with a poor prognosis. In this regard, identify clinicopathological predictors for Melanoma Lung Metastases (MLM) plays a pivotal role in clinical practice. Methods: We computer-searched the clinical records of all our patients registered in our melanoma database to identify patients that presented MLM. Kaplan-Meier product was used to estimate time to MELANOMA LUNG METASTASES (TMLM) and Overall Survival (OS); while the log-rank test was used to evaluate differences between the survival curves. Cox proportional hazards regression was performed in the analysis between clinicopathological features of the primary tumor and MLM. Results: A total of 63 patients with MLM were included in our analysis. Median TMLM was 27.4 months, while median OS was 55.5 months, with a Median Lung Metastases Survival (MLMS) of 10 months. Melanoma patients with a primary axial tumor (p&lt;0.001) and with an age ≤ 60 years (p=0.01) showed a better TMLM. While OS was statistically significant higher only in axial melanomas (p&lt;0.001), multivariate analysis showed that peripheral site of the primary tumor remained the main predictor to develop MLM, with a significant influence in TMLM and also in the long-term (p&lt;0.01 and p=0.04). Conclusions: Currently no standardized therapies exist for MLM. In this regard, the prevention of secondary recurrences plays a pivotal role in the management of melanoma patients. According to our results, peripheral melanoma is the main predictor for development of MLM