Lesion selection by melanoma high-risk consumers during skin self-examination using mobile teledermoscopy

Mobile teledermatoscopy (MTD) for the early detection of skin cancer uses smartphones with dermatoscope attachments to magnify, capture, and transfer images remotely.1 Using the asymmetry–color variation (AC) rule, consumers achieve dermoscopy sensitivity of 92.9% to 94.0% and specificity of 62.0% to 64.2% for melanoma.2 This pilot randomized trial assessed lesions of concern selected by consumers at high risk of melanoma using MTD plus the AC rule (intervention, n = 10) or the AC rule alone (control, n = 12) during skin self-examination (SSE). Also measured were lesion location patterns, lesions overlooked by participants, provisional clinical diagnoses, likelihood of malignant tumor, and participant pressure to excise lesions.

Clinical skin examination outcomes after a video-based behavioral intervention analysis from a randomized clinical trial

Importance Older men are at risk of dying of melanoma. Objective To assess attendance at and clinical outcomes of clinical skin examinations (CSEs) in older men exposed to a video-based behavioral intervention. Design, Setting, and Participants This was a behavioral randomized clinical trial of a video-based intervention in men aged at least 50 years. Between June 1 and August 31, 2008, men were recruited, completed baseline telephone interviews, and were than randomized to receive either a video-based intervention (n = 469) or brochures only (n = 461; overall response rate, 37.1%) and were again interviewed 7 months later (n = 870; 93.5% retention). Interventions Video on skin self-examination and skin awareness and written informational materials. The control group received written materials only. Main Outcomes and Measures Participants who reported a CSE were asked for the type of CSE (skin spot, partial body, or whole body), who initiated it, whether the physician noted any suspicious lesions, and, if so, how lesions were managed. Physicians completed a case report form that included the type of CSE, who initiated it, the number of suspicious lesions detected, how lesions were managed (excision, nonsurgical treatment, monitoring, or referral), and pathology reports after lesion excision or biopsy. Results Overall, 540 of 870 men (62.1%) self-reported a CSE since receiving intervention materials, and 321 of 540 (59.4%) consented for their physician to provide medical information (received for 266 of 321 [82.9%]). Attendance of any CSE was similar between groups (intervention group, 246 of 436 [56.4%]; control group, 229 of 434 [52.8%]), but men in the intervention group were more likely to self-report a whole-body CSE (154 of 436 [35.3%] vs 118 of 434 [27.2%] for control group; P = .01). Two melanomas, 29 squamous cell carcinomas, and 38 basal cell carcinomas were diagnosed, with a higher proportion of malignant lesions in the intervention group (60.0% vs 40.0% for controls; P = .03). Baseline attitudes, behaviors, and skin cancer history were associated with higher odds of CSE and skin cancer diagnosis. Conclusions and Relevance A video-based intervention may increase whole-body CSE and skin cancer diagnosis in older men. Trial Registration: anzctr.org.au Identifier: ACTRN12608000384358

Skin cancer detection by one click - are we any closer?

To the editor...

Characterisation of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes

The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline both in Australia and globally. Hence, the cellular and molecular pathways associated with UVR-induced photocarcinogenesis urgently need to be elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular the highly-mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which to some extent have limited their relevance to the in vivo situation. To address this, we characterised a 3-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically-relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB-irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53 and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration following photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage.

Interventions to decrease skin cancer risk in outdoor workers : update to a 2007 systematic review

BACKGROUND: Outdoor workers are at high risk of harmful ultraviolet radiation exposure and are identified as an at risk group for the development of skin cancer. This systematic evidence based review provides an update to a previous review published in 2007 about interventions for the prevention of skin cancer in outdoor workers. RESULTS: This review includes interventions published between 2007-2012 and presents findings about sun protection behaviours and/or objective measures of skin cancer risk. Six papers met inclusion criteria and were included in the review. Large studies with extended follow-up times demonstrated the efficacy of educational and multi-component interventions to increase sun protection, with some higher use of personal protective equipment such as sunscreen. However, there is less evidence for the effectiveness of policy or specific intervention components. CONCLUSIONS: Further research aimed at improving overall attitudes towards sun protection in outdoor workers is needed to provide an overarching framework.

Tissue viability imaging of skin microcirculation following exposure to whole body cryotherapy (-110°C) and cold water immersion (8°C)

Cryotherapy is currently used in various clinical, rehabilitative, and sporting settings. However, very little is known regarding the impact of cooling on the microcirculatory response. Objectives: The present study sought to examine the influence of two commonly employed modalities of cryotherapy, whole body cryotherapy (WBC; -110°C) and cold water immersion(CWI; 8±1°C), on skin microcirculation in the mid- thigh region. Methods: The skin area examined was a 3 × 3 cm located between the most anterior aspect of the inguinal fold and the patella. Following 10 minutes of rest, 5 healthy, active males were exposed to either WBC for 3 minutes or CWI for 5 minutes in a randomised order. Volunteers lay supine for five minutes after treatment, in order to monitor the variation of red blood cell (RBC) concentration in the region of interest for a duration of 40 minutes. Microcirculation response was assessed using a non-invasive, portable instrument known as a Tissue Viability imaging system. After a minimum of seven days, the protocol was repeated. Subjective assessment of the volunteer’s thermal comfort and thermal sensation was also recorded. Results: RBC was altered following exposure to both WBC and CWI but appeared to stabilise approximately 35 minutes after treatments. Both WBC and CWI affected thermal sensation (p < 0.05); however no betweengroup differences in thermal comfort or sensation were recorded (p > 0.05). Conclusions: As both WBC and CWI altered RBC, further study is necessary to examine the mechanism for this alteration during whole body cooling.

Prevention and treatment of acute radiation-induced skin reactions : a systematic review and meta-analysis of randomized controlled trials

Background Radiation-induced skin reaction (RISR) is a common side effect that affects the majority of cancer patients receiving radiation treatment. RISR is often characterised by swelling,redness, pigmentation, fibrosis, and ulceration, pain, warmth, burning, and itching of the skin. The aim of this systematic review was to assess the effects of interventions which aim to prevent or manage RISR in people with cancer. Methods We searched the following databases up to November 2012: Cochrane Skin Group Specialised Register, CENTRAL (2012, Issue 11), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), CINAHL (from 1981) and LILACS (from 1982). Randomized controlled trials evaluating interventions for preventing or managing RISR in cancer patients were included. The primary outcomes were development of RISR, and levels of RISR and symptom severity. Secondary outcomes were time taken to develop erythema or dry desquamation; quality of life; time taken to heal, a number of skin reaction and symptom severity measures; cost, participant satisfaction; ease of use and adverse effects. Where appropriate, we pooled results of randomized controlled trials using mean differences (MD) or odd ratios (OR) with 95% confidence intervals (CI). Results Forty-seven studies were included in this review. These evaluated six types of interventions (oral systemic medications; skin care practices; steroidal topical therapies; non-steroidal topical therapies; dressings and other). Findings from two meta-analyses demonstrated significant benefits of oral Wobe-Mugos E for preventing RISR (OR 0.13 (95% CI 0.05 to 0.38)) and limiting the maximal level of RISR (MD −0.92 (95% CI −1.36 to −0.48)). Another meta-analysis reported that wearing deodorant does not influence the development of RISR (OR 0.80 (95% CI 0.47 to 1.37)). Conclusions Despite the high number of trials in this area, there is limited good, comparative research that provides definitive results suggesting the effectiveness of any single intervention for reducing RISR. More research is required to demonstrate the usefulness of a wide range of products that are being used for reducing RISR. Future efforts for reducing RISR severity should focus on promising interventions, such as Wobe-Mugos E and oral zinc.

Collagen in the scarless fetal skin wound : detection with picrosirius-polarization

Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus heals scarlessly and the lamb heals with scar. The comparison of collagen structure between these two different mechanisms of healing may elucidate the process of scarless wound healing. Picrosirius staining followed by polarized light microscopy was used to visualize collagen fibers, with digital capture and analysis. Collagen deposition increased with fetal age and the fibers became thicker, changing from green (type III collagen) to yellow/red (type I collagen). The ratio of type III collagen to type I was high in the fetus (166), whereas the lamb had a much lower ratio (0.2). After burn, the ratios of type III to type I collagen did not differ from those in control skin for either fetus or lamb. The fetal tissue maintained normal tissue architecture after burn while the lamb tissue showed irregular collagen organization. In conclusion, the type or amount of collagen does not alter significantly after injury. Tissue architecture differed between fetal and lamb tissue, suggesting that scar development is related to collagen cross-linking or arrangement. This study indicates that healing in the scarless fetal wound is representative of the normal fetal growth pattern, rather than a "response" to burn injury.

Standardising corneal nerve fibre length for nerve tortuosity increases its association with measures of diabetic neuropathy

AIMS: Recent studies on corneal markers have advocated corneal nerve fibre length as the most important measure of diabetic peripheral neuropathy. The aim of this study was to determine if standardizing corneal nerve fibre length for tortuosity increases its association with other measures of diabetic peripheral neuropathy. METHODS: Two hundred and thirty-one individuals with diabetes with either predominantly mild or absent neuropathic changes and 61 control subjects underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10-g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length and corneal nerve fibre tortuosity were measured using corneal confocal microscopy. A tortuosity-standardised corneal nerve fibre length variable was generated by dividing corneal nerve fibre length by corneal nerve fibre tortuosity. Differences in corneal nerve morphology between individuals with and without diabetic peripheral neuropathy and control subjects were determined and associations were estimated between corneal morphology and established tests of, and risk factors for, diabetic peripheral neuropathy. RESULTS: The tortuosity-standardised corneal nerve fibre length variable was better than corneal nerve fibre length in demonstrating differences between individuals with diabetes, with and without neuropathy (tortuosity-standardised corneal nerve fibre length variable: 70.5 ± 27.3 vs. 84.9 ± 28.7, P < 0.001, receiver operating characteristic area under the curve = 0.67; corneal nerve fibre length: 15.9 ± 6.9 vs. 18.4 ± 6.2 mm/mm(2) , P = 0.004, receiver operating characteristic area under the curve = 0.64). Furthermore, the tortuosity-standardised corneal nerve fibre length variable demonstrated a significant difference between the control subjects and individuals with diabetes, without neuropathy, while corneal nerve fibre length did not (tortuosity-standardised corneal nerve fibre length variable: 94.3 ± 27.1 vs. 84.9 ± 28.7, P = 0.028; corneal nerve fibre length: 20.1 ± 6.3 vs. 18.4 ± 6.2 mm/mm(2) , P = 0.084). Correlations between corneal nerve fibre length and established measures of neuropathy and risk factors for neuropathy were higher when a correction was made for the nerve tortuosity. CONCLUSIONS: Standardizing corneal nerve fibre length for tortuosity enhances the ability to differentiate individuals with diabetes, with and without neuropathy.

Retinal nerve fibre layer thickness is associated with higher risk of foot ulceration in diabetic peripheral neuropathy

Purpose To evaluate the association between retinal nerve fibre layer (RNFL) thickness and diabetic peripheral neuropathy in people with type 2 diabetes, and specifically those at higher risk of foot ulceration. Methods RNFL thicknesses was measured globally and in four quadrants (temporal, superior, nasal and inferior) at 3.45 mm diameter around the optic nerve head using optical coherence tomography (OCT). Severity of neuropathy was assessed using the Neuropathy Disability Score (NDS). Eighty-two participants with type 2 diabetes were stratified according to NDS scores (0-10) as: none, mild, moderate, and severe neuropathy. A control group was additionally included (n=17). Individuals with NDS≥ 6 (moderate and severe neuropathy) have been shown to be at higher risk of foot ulceration. A linear regression model was used to determine the association between RNFL and severity of neuropathy. Age, disease duration and diabetic retinopathy levels were fitted in the models. Independent t-test was employed for comparison between controls and the group without neuropathy, as well as for comparison between groups with higher and lower risk of foot ulceration. Analysis of variance was used to compare across all NDS groups. Results RNFL thickness was significantly associated with NDS in the inferior quadrant (b= -1.46, p=0.03). RNFL thicknesses globally and in superior, temporal and nasal quadrants did not show significant associations with NDS (all p>0.51). These findings were independent of the effect of age, disease duration and retinopathy. RNFL was thinner for the group with NDS ≥ 6 in all quadrants but was significant only inferiorly (p<0.005). RNFL for control participants was not significantly different from the group with diabetes and no neuropathy (superior p=0.07, global and all other quadrants: p>0.23). Mean RNFL thickness was not significantly different between the four NDS groups globally and in all quadrants (p=0.08 for inferior, P>0.14 for all other comparisons). Conclusions Retinal nerve fibre layer thinning is associated with neuropathy in people with type 2 diabetes. This relationship is strongest in the inferior retina and in individuals at higher risk of foot ulceration.

Educational programmes for primary prevention of skin cancer (Protocol)

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of education programmes for skin cancer prevention in the general population. Description of the condition Skin cancer is a term that includes both melanoma and keratinocyte cancer. Keratinocyte cancer (also known as nonmelanoma skin cancer) generally refers to basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), although it also includes other rare cutaneous neoplasms (Madan 2010). Skin cancer is the most common cancer in populations of predominantly fair-skinned people (Donaldson 2011; Lomas 2012; Stern 2010), with incidence increasing (Garbe 2009; Leiter 2012). There are variations in annual incidence rates between these populations, with Australia reporting the highest rate of skin cancer in the world (Lomas 2012). In 2012, the estimated age-standardised incidence rate for melanoma was almost 63 per 100,000 people for Australian men, and 40 per 100,000 people for Australian women (AIHW 2012). In Europe, incidence rates range from 10 to 15 per 100,000 people (Garbe 2009; Lasithiotakis 2006), with rates highest amongst men (Stang 2006). In the United States, incidence rates are approximately 18 per 100,000 people (Garbe 2009),with the highest rates reported forwomen (Bradford 2010). Keratinocyte cancer is much more common than melanoma. In 2012, the estimated Australian age-standardised rates for BCCand SCC were 884 and 387 per 100,000 people, respectively (Staples 2006). The cumulative three-year risk of developing a subsequent keratinocyte cancer is 18% for SCC and 44% for BCC (Marcil 2000).

Proteases : common culprits in human skin disorders

Recent findings from the clinic and the laboratory have transformed the way proteases and their inhibitors are perceived in the outermost layer of the skin, the epidermis. It now appears that an integrated proteolytic network operates within the epidermis, comprising more than 30 enzymes that carry out a growing list of essential functions. Equally, defective regulation or execution of protease-mediated processes is emerging as a key contributor to diverse human skin pathologies, and in recent years the number of diseases attributable to aberrant proteolytic activity has more than doubled. Here, we survey the different roles of proteases in epidermal homeostasis (from processing enzymes to signalling molecules) and explore the spectrum of rare and common human skin disorders where proteolytic pathways are dysregulated.

Proteases and proteomics : cutting to the core of human skin pathologies

Preserving the integrity of the skin's outermost layer (the epidermis) is vital for humans to thrive in hostile surroundings. Covering the entire body, the epidermis forms a thin but impenetrable cellular cordon that repels external assaults and blocks escape of water and electrolytes from within. This structure exists in a perpetual state of regeneration where the production of new cellular subunits at the base of the epidermis is offset by the release of terminally differentiated corneocytes from the surface. It is becoming increasingly clear that proteases hold vital roles in assembling and maintaining the epidermal barrier. More than 30 proteases are expressed by keratinocytes or infiltrating immune cells and the activity of each must be maintained within narrow limits and confined to the correct time and place. Accordingly, over- or under-exertion of proteolytic activity is a common factor in a multitude of skin disorders that range in severity from relatively mild to life-threatening. This review explores the current state of knowledge on the involvement of proteases in skin diseases and the latest findings from proteomic and transcriptomic studies focused on uncovering novel (patho)physiological roles for these enzymes.