Clinical implications of acquired braf inhibitors resistance in melanoma

Understanding the role of mitogen-activated protein kinase (MAPK) pathway-activating mutations in the development and progression of melanoma and their possible use as therapeutic targets has substantially changed the management of this neoplasm, which, until a few years ago, was burdened by severe mortality. However, the presence of numerous intrinsic and extrinsic mechanisms of resistance to BRAF inhibitors compromises the treatment responses\u2019 effectiveness and durability. The strategy of overcoming these resistances by combination therapy has proved successful, with the additional benefit of reducing side effects derived from paradoxical activation of the MAPK pathway. Furthermore, the use of other highly specific inhibitors, intermittent dosing schedules and the association of combination therapy with immune checkpoint inhibitors are promising new therapeutic strategies. However, numerous issues related to dose, tolerability and administration sequence still need to be clarified, as is to be expected from currently ongoing trials. In this review, we describe the clinical results of using BRAF inhibitors in advanced melanoma, with a keen interest in strategies aimed at overcoming resistance

Postoperative pain surveys in Italy from 2006 and 2012. (POPSI and POPSI-2)

OBJECTIVE: Despite established standards, effective treatments, and evidence-based guidelines, postoperative pain control in Italy and other parts of the world remains suboptimal. Pain control has been recognized as a fundamental human right. Effective treatments exist to control postsurgical pain. Inadequate postoperative analgesia may prolong the length of hospital stays and may adversely impact outcomes. MATERIALS AND METHODS: The same multiple-choice survey administered at the SIAARTI National Congress in Perugia in 2006 (n=588) was given at the SIAARTI National Congress in Naples, Italy in 2012 (n=635). The 2012 survey was analysed and compared to the 2006 results. RESULTS: Postoperative pain control in Italy was less than optimal in 2006 and showed no substantial improvements in 2012. Geographical distinctions were evident with certain parts of Italy offering better postoperative pain control than other. Fewer than half of hospitals represented had an active Acute Pain Service (APS) and only about 10% of postsurgical patients were managed according to evidence-based guidelines. For example, elastomeric pumps for continuous IV infusion are commonly used in Italy, although patient-controlled analgesia systems are recommended in the guidelines. The biggest obstacles to optimal postoperative pain control reported by respondents could be categorized as organizational, cultural, and economic. CONCLUSIONS: There is considerable room for improvement in postoperative pain control in Italy, specifically in the areas of clinical education, evidence-based treatments, better equipment, and implementation of active APS departments in more hospitals. Two surveys taken six years apart in Italy reveal, with striking similarity, that there are many unmet needs in postoperative pain control and that Italy still falls below European standards for postoperative pain control

The challenge of perioperative pain management in opioid-tolerant patients

The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone

Efficacy of topical imiquimod 3.75% in the treatment of actinic keratosis of the scalp in immunosuppressed patients: our case series

AbstractBackground: Actinic keratoses (AK) represent common cutaneous lesions, appearing in 'Field cancerization areas' and potentially evolving toward invasive neoplasm. Immunosuppressed patients ..

Nicotinamide and calcipotriol counteract UVB-induced photoaging on primary human dermal fibroblasts

Background: Photoaging is mainly caused by ultraviolet radiations inasmuch they can damage the DNA, trigger ROS production, and activate p53/p21 pathway, which cause cell cycle arrest and senescence. The accumulationof senescent cells within the dermis contributes to tissue deregulation and skin carcinogenesis. However, the use of photoprotector molecules could reduce UV-induced damages and prevent photoaging. Therefore, the aim of this study is to evaluate whether the active forms of vitamin B3 (nicotinamide) and the analog of vitamin D3 (calcipotriol) might protect primary human dermal fibroblasts (HDFs) from UVB-induced photoaging. Methods: HDFs were isolated from a healthy adult donor and stimulated with nicotinamide (25 μM) and calcipotriol (100 nM) for 24h before UVB exposure, and then, cultured for further 24h on vitamin-supplemented media. Then, cell viability, ROS production, DNA damages, senescence markers, protein and gene expression were evaluated. Results: HDFs treated with nicotinamide and calcipotriol showed better proliferation properties and lower DNA damages due to a reduced UVB-induced ROS production. Consequently, p53/p21 pathway was less active which enhanced cell cycle progression and reduced senescence and cell death. Conclusions: Overall, our results suggest that nicotinamide and calcipotriol can counteract UVB-induced effects responsible for the onset of skin photoaging

Non-Melanoma Skin Cancer: news from microbiota research

Recently, research has been deeply focusing on the role of the microbiota in numerous diseases, either affecting the skin or other organs. What it is well established is that its dysregulation promotes several cutaneous disorders (i.e. psoriasis and atopic dermatitis). To date, little is known about its composition, mediators and role in the genesis, progression and response to therapy of Non-Melanoma Skin Cancer (NMSC). Starting from a bibliographic study, we classified the selected articles into four sections: i) normal skin microbiota; ii) in vitro study models; iii) microbiota and NMSC and iv) probiotics, antibiotics and NMSC. What has emerged is how skin microflora changes, mainly represented by increases of Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa strains, modifications in the mutual quantity of \u3b2-Human papillomavirus genotypes, of Epstein Barr Virus and Malassezia or candidiasis, may contribute to the induction of a state of chronic self-maintaining inflammation, leading to cancer. In this context, the role of S. aureus and that of specific antimicrobial peptides look to be prominent. Moreover, although antibiotics may contribute to carcinogenesis, due to their ability to influence the microbiota balance, specific probiotics, such as Lacticaseibacillus rhamnosus GG, Lactobacillus johnsonii NCC 533 and Bifidobacteria spp., may be protective