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1.
Topical and Systemic Modalities for Chemoprevention of Nonmelanoma Skin Cancer.
Nemer, KM, Council, ML
Dermatologic clinics. 2019;(3):287-295
Abstract
Chemoprevention of nonmelanoma skin cancer should be considered in patients likely to develop numerous, invasive, or metastatic nonmelanoma skin cancers. This article reviews the various topical and systemic substances studied as chemopreventive agents.
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2.
Exposure to Trace Elements and Risk of Skin Cancer: A Systematic Review of Epidemiologic Studies.
Matthews, NH, Fitch, K, Li, WQ, Morris, JS, Christiani, DC, Qureshi, AA, Cho, E
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2019;(1):3-21
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Abstract
Exposure to environmental trace elements has been studied in relation to many cancers. However, an association between exposure to trace elements and skin cancer remains less understood. Therefore, we conducted a systematic review of published epidemiologic literature examining the association between exposure to trace elements, and risk of melanoma and keratinocyte carcinoma in humans. We identified epidemiologic studies investigating exposure to arsenic, cadmium, chromium, copper, iron, selenium, and zinc and risk of skin cancer in humans. Among the minerals, arsenic, selenium, and zinc had more than five studies available. Exposure to arsenic was associated with increased risk of keratinocyte carcinoma, while too few studies existed on melanoma to draw conclusions. Exposure to selenium was associated with possible increased risk of keratinocyte carcinoma. Studies of zinc and skin cancer were case-control in design and were found to have inconsistent associations. The data on the association between cadmium, chromium, copper, and iron and risk of skin cancer remain too sparse to draw any conclusions. In summary, epidemiologic studies on exposure to trace elements and cutaneous malignancies are limited. Studies with larger sample sizes and prospective designs are warranted to improve our knowledge of trace elements and skin cancer.
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3.
Topical treatment with oleocanthal extract in reducing inflammatory reactions after photodynamic therapy: a prospective quasi-experimental pilot study.
Segura Palacios, JM, Blázquez Sánchez, N, Rivas Ruiz, F, Aguilar Bernier, M, Ramírez López, B, Sánchez, MEF, de Troya Martín, M
Complementary therapies in medicine. 2019;:298-301
Abstract
OBJECTIVE Photodynamic therapy (PDT) is an effective treatment against skin field cancerization. Its main side effect is local inflammation in the treated area. The phenolic compound oleocanthal (decarboxy methyl ligstroside aglycone), which is present in extra virgin olive oil (EVOO), has anti-inflammatory properties. The purpose of this study was to evaluate the topical efficacy of an oily fluid enriched with oleocanthal (OC) extract, in comparison with a conventional oily fluid, in reducing the degree of inflammatory reaction after conventional PDT. METHODS Quasi-experimental pilot study, before-after with a control group, performed with a cohort of consecutive patients diagnosed with actinic keratosis/field cancerization (AK/FC) in the forehead and/or scalp, treated by PDT. The study was carried out from April 2016 to November 2017 at a speciality hospital in southern Spain. A group of 24 consecutive patients received the topical application, three times daily for one week, of an emollient oily fluid in the area treated with PDT. Subsequently, another group, of 23 consecutive patients, received the same treatment pattern with an oily fluid enriched with OC extract. The post-PDT inflammatory reaction was measured by an independent member of the hospital's dermatology department, using the following visual scale of erythema (from 0 to 4).The assessment was conducted at 30 min and at 48 h post-PDT. RESULTS In the assessment at 48 h after treatment, the inflammation had improved more among the patients treated with OC (median: 25%, 95%CI: -5.3 to 28.5) than in the non-OC group (median: 0%; 95%CI: -45.2 to -6.2). The difference was statistically significant (p<0.01), and the Cohen's d value was 0.89 (large effect). At three months after PDT, a complete response had been obtained by 60.9% of the patients treated with OC compared to 29.2% of the non-OC group, and the difference was close to statistical significance (p=0.059). CONCLUSIONS The topical application of an oily fluid enriched with OC extract achieved a greater reduction in post-PDT cutaneous inflammation and a better treatment response, in comparison with the application of a conventional oily fluid.
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4.
Improving in vitro photodynamic therapy through the development of a novel iron chelating aminolaevulinic acid prodrug.
Curnow, A, Perry, A, Wood, M
Photodiagnosis and photodynamic therapy. 2019;:157-165
Abstract
BACKGROUND Photodynamic therapy (PDT) is a light activated drug therapy that can be used to treat a number of cancers and precancers. It is particularly useful in its topical form in dermatology but improvement of efficacy is required to widen its application. METHODS An ester between aminolaevulinic acid (ALA) and CP94 was synthesised (AP2-18) and experimentally evaluated to determine whether protoporphyrin IX (PpIX)-induced PDT effectiveness could be improved. A biological evaluation of AP2-18 was conducted in cultured human primary cells with both PpIX fluorescence and cell viability (as determined via the neutral red assay) being assessed in comparison to the PpIX prodrugs normally utilised in clinical practice (aminolaevulinic acid (ALA) or its methyl ester (MAL)) either administered alone or with the comparator iron chelator, CP94. RESULTS No significant dark toxicity was observed in human lung fibroblasts but AP2-18 significantly increased PpIX accumulation above and beyond that achieved with ALA or MAL administration +/- CP94 in both human dermal fibroblasts and epithelial squamous carcinoma cells. On light exposure, the combined hydroxypyridinone iron chelating ALA prodrug AP2-18 generated significantly greater cytotoxicity than any of the other treatment parameters investigated when the lowest concentration (250 μM) was employed. CONCLUSIONS Newly synthesised AP2-18 is therefore concluded to be an efficacious prodrug for PpIX-induced PDT in these dermatologically relevant human cells, achieving enhanced effects at lower concentrations than currently possible with existing pharmaceuticals.
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5.
Reviewing the effects of thiazide and thiazide-like diuretics as photosensitizing drugs on the risk of skin cancer.
Kreutz, R, Algharably, EAH, Douros, A
Journal of hypertension. 2019;(10):1950-1958
Abstract
BACKGROUND Thiazide diuretics and particularly hydrochlorothiazide were recently linked to an increased risk of skin cancer, which was attributed to the photosensitizing properties of these drugs. Given the widespread use of thiazide diuretics, a potential skin cancer promoting effect would impose an important public health concern. OBJECTIVE To critically appraise in a narrative review, the association between use of thiazide and thiazide-like diuretics and risk of skin cancer. METHODS We evaluated chemical structures and photosensitizing potential of selected thiazide and thiazide-like diuretics. Moreover, we searched PubMed up to December 2018 for observational studies assessing the association between use of thiazide or thiazide-like diuretics and risk of skin cancer. Study quality was assessed for major methodological biases. RESULTS Commonly used thiazide and thiazide-like diuretics carry resonating structural components, such as sulfonamide groups that contribute to their photosensitizing activity. Overall, 13 observational (9 case-control, 4 cohort) studies assessed the association between use of different thiazide or thiazide-like diuretics and risk of several skin cancer types. Of those, nine studies showed positive associations ranging from 3% increased risk for bendroflumethiazide and basal cell carcinoma to 311% increased risk for thiazide diuretics and squamous cell carcinoma. All studies had important design-related methodological limitations including potential confounding by indication, detection bias, and time-window bias. CONCLUSION Commonly used thiazide and thiazide-like diuretics have photosensitizing potential, and some observational studies with important methodological limitations have linked their use to an increased risk of skin cancer. Well designed observational studies are needed to provide more solid evidence on this possible association.
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6.
What's New in Photoprotection: A Review of New Concepts and Controversies.
Yeager, DG, Lim, HW
Dermatologic clinics. 2019;(2):149-157
Abstract
Cumulative ultraviolet exposure plays a critical role in photodamage. Recent advancements in photomedicine have resulted in a more thorough understanding of these mechanisms. Despite this, the adoption of routine sun protective practices is commonly not undertaken regularly by a large proportion of the public. Various obstacles exist that contribute to the public's nonadherence to these practices. Sunscreens, which are an integral component in all photoprotective regimens, have been questioned recently in terms of their safety. The aim of this article is to provide an overview of new concepts in photoprotection and also address current controversies pertaining to sunscreens.
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7.
[Hydrochlorothiazide and skin cancer].
Olde Engberink, RHG, van der Hoeven, NV, Zwinderman, AH, van den Born, BH
Nederlands tijdschrift voor geneeskunde. 2019
Abstract
Hydrochlorothiazide and skin cancer Hydrochlorothiazide is a frequently prescribed diuretic with known photosensitizing properties. Recently, a large case-control study in a Danish population found an association between the use of hydrochlorothiazide and an increased risk of developing non-melanoma skin cancer. These data suggest that it may be wise to limit the use of hydrochlorothiazide for the treatment of hypertension. We reviewed the current literature to examine whether a causal relationship between hydrochlorothiazide and non-melanoma skin cancer exists. We consider that the evidence for a causal relationship is limited and contradicting. Moreover, we found that other antihypertensive agents such as calcium blockers and angiotensin receptor blockers are also associated with basal cell carcinoma. Based on the current literature, there seems to be insufficient evidence to advice against the use of hydrochlorothiazide.
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8.
Potential use of melatonin in skin cancer treatment: A review of current biological evidence.
Pourhanifeh, MH, Mahdavinia, M, Reiter, RJ, Asemi, Z
Journal of cellular physiology. 2019;(8):12142-12148
Abstract
Skin cancer, particularly melanoma, is a leading cause of death worldwide. The therapeutic methods for this malignancy are not effective, and due to the side effects of these treatments, applying an appropriate alternative or complementary treatment is important. According to available data, melatonin as the main product of the pineal gland has oncostatic and antitumoral properties. Also, melatonin acts as an anti-inflammatory and reactive oxygen species inducer agent which suppresses the growth of tumors. It also has apoptosis induction characteristics through regulating signaling pathways, including heat shock protein 70, nuclear factor-erythroid 2 p45-related factor 2 and others. Thus, adding melatonin to chemo- and radiotherapy may have synergistic therapeutic effects and increase the survival time in patients with skin cancer. Few clinical studies have evaluated the efficacy of melatonin in skin cancer. Based on the related mechanisms, this review discusses about how melatonin may improve outcomes in skin cancer patients.
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9.
Sun protection behavior after diagnosis of high-risk primary melanoma and risk of a subsequent primary.
von Schuckmann, LA, Wilson, LF, Hughes, MCB, Beesley, VL, Janda, M, van der Pols, JC, Smithers, BM, Khosrotehrani, K, Green, AC
Journal of the American Academy of Dermatology. 2019;(1):139-148.e4
Abstract
BACKGROUND Melanoma survivors are at high risk of further primary melanomas. OBJECTIVE To assess sun behavior after melanoma diagnosis and in relation to further primary melanomas. METHODS We applied repeated measures latent class analysis to reported primary prevention behavior at time of diagnosis and every 6 months for 2 years after diagnosis in patients with clinical stage IB or II melanoma. Correlates of behavior trajectories and risk of subsequent primaries were determined by using multivariable logistic and Cox regression analyses, respectively. RESULTS Among the 448 male and 341 female patients, sunscreen use fell into 3 trajectories: stable never-use (26% of males and 12% of females), stable sometimes-use (35% of males and 29% of females), and increased to often-use (39% of males and 59% of females). Most reduced their weekend sun exposure, but in 82% of males and 69% of females it remained increased. Males, smokers, the less educated, those who tanned, and those not self-checking their skin were more likely to have trajectories of inadequate protection. Patients with a history of melanoma before the study doubled their risk of another primary melanoma in the next 2 years if sunscreen use in that time was inadequate (hazard ratio, 2.45; 95% confidence interval, 1.00-6.06). LIMITATIONS Patient-reported data are susceptible to recall bias. CONCLUSION Our results may assist clinicians in identifying patients not using adequate sun protection and providing information for patient counseling.
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10.
Present and future perspectives of photodynamic therapy for cutaneous squamous cell carcinoma.
Keyal, U, Bhatta, AK, Zhang, G, Wang, XL
Journal of the American Academy of Dermatology. 2019;(3):765-773
Abstract
Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer. Surgery remains the main stay of treatment, but some patients are not eligible for surgery and, more importantly, lesions at critical sites need nonsurgical approaches for tissue preservation. In this context, photodynamic therapy (PDT) has been extensively studied as noninvasive or minimally invasive treatment, and studies have shown promising results in terms of safety, efficacy, and cosmetic outcome. Also, studies have proposed different mechanism for its efficacy. However, human studies demonstrating its efficacy are limited in terms of sample size and tumor depth of invasion. Good results are mainly seen in case reports of microinvasive SCC, which is defined as SCC limited to papillary dermis. This inadequacy is due to inadequate penetration of topically applied photosensitizers through keratinized tumor surfaces. To overcome these hurdles, pretreatment with lasers or microneedles and encapsulation of photosensitizers into nanoparticles have been tried. Hence, the present article will discuss studies that have demonstrated the efficacy and safety of PDT for cutaneous SCC, studies that have postulated the mechanism of action of PDT, agents that have been used as PDT enhancers, and finally, the recent use of adjuvant therapy in combination with PDT.