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Actinic keratoses (AK) may occur in all sun-exposed skin areas. Those occurring outside the head area are generally more resistant to treatment than those on the face.To determine efficacy and safety of BF-200 ALA versus vehicle in the treatment of mild-to-severe AK located on extremities, trunk, and neck with red light photodynamic therapy (PDT).This phase III study had an intra-individual design with 50 patients in 6 centers in Germany. Each patient received a maximum of 2 field-directed PDTs. Clinical end points and 1-year follow-up results were recorded.BF-200 ALA was superior to the vehicle with respect to total lesion clearance rates (86.0% vs 32.9%; P .0001) and patient complete clearance per patient's side (67.3% vs 12.2%, P .0001). One-year overall lesion recurrence rate was 14.1% versus 27.4% (BF-200 ALA vs vehicle; P = .0068). Patients were more satisfied by the cosmetic outcome of BF-200 ALA/PDT than the vehicle/PDT. Adverse events were consistent with the known safety profile of BF-200 ALA/PDT.Small number of severe lesions; limited sample size; unbalanced but representative distribution of AK.BF-200 ALA showed significantly higher AK clearance rates on extremities, trunk, and neck than the vehicle and was well tolerated.

Background: Dynamic optical coherence tomography (D-OCT) allows in vivo visualization of blood vessels in the skin and in malignant tumours. Vessel patterns in malignant melanoma may be associated with tumour stage. Objective: The aim of this study was to describe blood vessel patterns in melanomas and to correlate them with stage. Methods: One hundred fifty-nine malignant melanomas were assessed in a multicentre study. Every tumour was imaged using D-OCT prior to surgery and histologic evaluation. The tumour data such as thickness and ulceration as well as the staging at primary diagnosis and a follow-up of at least 40 months resulted in a stage classification. The vessel patterns were assessed according to predefined categories, compared with healthy adjacent skin, and correlated to stage. Results: Melanomas contained more blood vessels in different patterns compared with healthy adjacent skin. In particular, irregular vascular shapes such as blobs, coils, curves and serpiginous vessels were more common in melanomas. In addition, these patterns were significantly more often found in high-risk and metastatic melanomas than in low-risk lesions. Conclusion: In melanomas, the density of the blood vessels is increased, and irregular vascular patterns are more frequent. At higher stages, especially in metastatic melanomas, these atypical vessels are significantly more common.

Simple Summary The assessment of actinic keratoses (AKs) in prevention and therapeutic trials, as well as clinical practice, could significantly benefit from the incorporation of non-invasive imaging technology. Such technology has the potential to enhance the objective evaluation of clinical and subclinical AKs with the added advantage of sequential monitoring. In vivo reflectance confocal microscopy (RCM) allows for the non-invasive imaging of AKs at a cellular level. We aimed to establish an in in vivo RCM protocol for AK response monitoring, ultimately leading to more reliable characterization of longitudinal responses and therapy optimization. Abstract Reflectance confocal microscopy (RCM) presents a non-invasive method to image actinic keratosis (AK) at a cellular level. However, RCM criteria for AK response monitoring vary across studies and a universal, standardized approach is lacking. We aimed to identify reliable AK response criteria and to compare the clinical and RCM evaluation of responses across AK severity grades. Twenty patients were included and randomized to receive either cryotherapy (n = 10) or PDT (n = 10). Clinical assessment and RCM evaluation of 12 criteria were performed in AK lesions and photodamaged skin at baseline, 3 and 6 months. We identified the RCM criteria that reliably characterize AK at baseline and display significant reduction following treatment. Those with the highest baseline odds ratio (OR), good interobserver agreement, and most significant change over time were atypical honeycomb pattern (OR: 12.7, CI: 5.7–28.1), hyperkeratosis (OR: 13.6, CI: 5.3–34.9), stratum corneum disruption (OR: 7.8, CI: 3.5–17.3), and disarranged epidermal pattern (OR: 6.5, CI: 2.9–14.8). Clinical evaluation demonstrated a significant treatment response without relapse. However, in grade 2 AK, 10/12 RCM parameters increased from 3 to 6 months, which suggested early subclinical recurrence detection by RCM. Incorporating standardized RCM protocols for the assessment of AK may enable a more meaningful comparison across clinical trials, while allowing for the early detection of relapses and evaluation of biological responses to therapy over time.

Background and objectives Energy-based devices have been widely applied for skin ablation. A novel ablation technique based on thermomechanical principles (Tixel© ) has been recently developed. The aim of this study was to examine the wound-healing process and clinical aspects after thermomechanical skin ablation. Study design/materials and methods Six female participants were treated with Tixel© on healthy skin of the dorsal side of the right forearm in a single session with a 600 µm protrusion and 12 milliseconds pulse. The treated area was examined with confocal laser scanning microscopy on day 1, 2, 7, and 14 after treatment. Clinical symptoms were evaluated at the same time-points. Results All patients developed erythema and mild edema on the treated areas, which completely disappeared within 14 days. No post-inflammatory hyperpigmentation or scarring was observed. Thermomechanical skin ablation resulted in the formation of homogeneous micro-ablation zones. Two weeks after ablation, the honeycomb patterns of the epidermis in all examined layers was thoroughly restored. Thus, wound-healing was completed. Conclusions Wound healing after thermomechanical skin ablation is much faster compared with other fractionated ablation methods. Treatment intervals of 2-4 weeks could be recommended. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

Particle separation from gases is an important unit operation in manifold industrial applications, such as those conducted in environmental protection. For analysis of particle penetration and separation in fiber filters, standard dust particles (Al2O3) were loaded in the gas flow of a filter test facility and deposited within new and uncharged fiber filters. The loaded filters were analyzed by micro-computer tomography and scanning electron microscopy. Three-dimensional tomograms of the samples show an exponential decay of the penetration depth of the particles. This dependency is confirmed by simulations conducted using the discrete element method coupled with computational fluid dynamics within unloaded and loaded fiber structures. Microscale processes of particle separation at the fibers as well as the filtration efficiency and time-dependent filtering process are derived from the simulations. Local particle clustering in the filter medium and partial filter clogging are thus identified.

Introduction: Fractionated radiofrequency (RF) tissue tightening is an alternative method to fractionated laser treatment of skin wrinkling, laxity and acne scars, with reduced risk of scarring or persistent pigmentation. The aim of this study was to evaluate and quantify the wound healing process after RF treatment. Materials and methods: 12 patients were treated with a 64-pin fractional bipolar RF device with 60 mJ/pin applied energy. Confocal laser scanning microscopy (CLSM) examination was performed on day 1, day 2, day 7 and day 14 after treatment. Clinical wound healing process was measured and expressed as a percentage. Results: All patients developed erythema, mild edema and crusts at the treated areas. Two weeks after treatment clinical symptoms resolved. During ablation patients reported moderate pain. Directly after ablation microscopic ablation zones could be detected in CLSM. Measurement of MAZ at epidermis, dermo–epidermal junction and papilary dermis showed a constant diameter until two weeks after treatment. Re-epithelization of the MAZ could be detected already 1 week after treatment. However, 2 weeks after ablation the honeycomb pattern of the epidermis was not yet completely restored. Discussion: Bipolar fractionated RF treatment demonstrates clinically a rapid wound healing response. The subepidermal remodelling process still ongoing after 14 days, showing new granulation tissue. Therefore, treatment intervals of at least 14 days should be recommended to allow completion of the remodelling process.

Background Dynamic optical coherence tomography (D-OCT) has recently been introduced in dermatology. In contrast to 'Standard' OCT imaging, which exclusively relies on the morphological analysis of the tissue, D-OCT allows the in vivo visualization of blood flow. Preliminary D-OCT data showed differences in the vascularization of nevus to melanoma transition, suggesting that this technology may help to differentiate between benign and malignant lesions. Objective Several factors may influence the quality of D-OCT imaging. Therefore, standard operating procedures as well as a common terminology are required for better validation and comparison of the images. Methods Here, we present practical guidelines for optimal image acquisition and a proposed terminology on vascular patterns observed by D-OCT. Results Dynamic OCT allows the morphologic distinction of different vascular shapes (e.g. dots, blobs, curves, lines), their distribution and organization within skin lesions. Conclusion D-OCT adds functional information on skin microvasculature and the vascular networks within lesions.

BACKGROUND Basal cell carcinomas (BCCs) have previously been treated off-label with ingenol mebutate (IM). Ablative fractional laser (AFL) may improve efficacy of IM by increasing drug uptake in the tumour. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) detect BCC non-invasively. Our aim was to investigate BCC response and tolerability after combined AFL and IM treatment of low-risk BCCs. METHODS Twenty patients with histologically verified superficial (n = 7) and nodular (n = 13) BCCs were treated with combined fractional CO2 -laser (10 600 nm) and IM 0.015% or 0.05%, the concentration depending on anatomical location. BCC response was evaluated clinically, by OCT and RCM at day 29 and 90 after first treatment, and histologically at day 90. Treatment was repeated at day 29 if BCC persisted. Local skin reactions (LSRs) were assessed using LSR scale at all visits. RESULTS At day 29, 18/20 patients received a second treatment due to residual BCC detected clinically, by OCT or RCM. OCT and RCM presented subclinical BCCs in five of 20 cases (25%). At day 90, overall histological cure rate was 70%, corresponding to clinical (65%) and OCT/RCM (60%) cure rates, and agreement between evaluation methods was substantial (kappa ≥ 0.796, P

Background Drug-induced immunosuppression is necessary to prevent rejection of the foreign organ in transplanted patients, but neoplastic and virus-associated skin diseases are frequent complications. Reflectance confocal microscopy (RCM) recently emerged as a promising tool for the early diagnosis of skin lesions. Materials and methods A total of 61 skin lesions, among them 20 basal cell carcinomas, six Bowen's diseases, 23 actinic keratoses, and 12 verrucae, were analyzed. All lesions were clinically evaluated followed by RCM evaluation by two independent dermatologists and histological examination. Results For the diagnosis of basal cell carcinoma, a sensitivity of 100% by both investigators (INV I + II) and a specificity of 100% by INV I and 80% by INV II were achieved. The sensitivity average rate for RCM features reached by both investigators ranged between 60% and 100%, and the specificity between 55% and 90%. For the diagnosis of actinic keratosis, a concordant sensitivity of 94.4% and a specificity of 80% (INV I) and 60% (INV II) were detected. The sensitivity average rate of specific RCM criteria ranged between 72.3% and 97.2%, whereas specificity ranged between 20% and 90%. Regarding verrucae, RCM confirmed the histological diagnosis with a sensitivity of 85.7% (INV I) and 100% (INV II), while specificity was 100% and 80%, respectively. Conclusion Reflectance confocal microscopy resulted to be a reliable tool for the noninvasive diagnosis of neoplastic and virus-associated skin changes in organ transplant recipients. Nevertheless, given the frequency and diagnostic complexity of the hyperkeratotic lesions occurring post-transplantation, larger cohorts of patients are required to confirm and consolidate these findings.

The routine diagnostic procedure of actinic keratosis (AK) and invasive squamous cell carcinoma (SCC) is a histological examination after taking a biopsy. In the past decades, non-invasive optical methods for skin examination have been developed. Patients with clinical diagnosis of AK or SCC were examined. The morphological criteria were determined for healthy, AK and SCC skin and compared for statistically significant differences. In this study, the applicability of multiphoton tomography (MPT) as an in vivo diagnostic tool for AK and SCC was evaluated. Changes in the morphology of the keratinocytes such as broadened epidermis, large intercellular spaces, enlarged nucleus and a large variance in cell shape could easily be recognized. The cell nuclei of AK and SCC were significantly larger compared to healthy skin cells in all cell layers. The nucleus-cytoplasm ratio was also significantly higher for AK and SCC than for the healthy skin cells. It was even higher in SCC compared to spinous and basal cell layer of AK. The cell density in AK and SCC was significantly lower than in the basal and spinous cell layers of healthy skin. In SCC, the cell density was significantly lower than in AK. Concerning the intercellular spaces, significant differences were found for AK and healthy skin in spinous and basal cell layer and for SCC compared to AK and healthy skin. In this study, MPT proved to be a valuable non-invasive imaging method for in vivo detection and discrimination of AK and SCC from healthy skin.

Background: Basal cell carcinoma (BCC) represents the most common nonmelanoma skin cancer worldwide, affecting mainly adult, fair-skinned individuals. The World Health Organization distinguishes aggressive and nonaggressive forms, of which prototypical variants of the latter are primary nodular and superficial BCC. Objective: To demonstrate noninferiority of BF-200 ALA (a nanoemulsion gel containing 5-aminolaevulinic acid) compared with MAL (a cream containing methyl aminolaevulinate) in the treatment of nonaggressive BCC with photodynamic therapy (PDT). Noninferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF-200 ALA was no worse than that for MAL, within a statistical margin of = -15%. Methods: The study was a randomized, phase III trial performed in Germany and the U.K. with ongoing 5-year follow-up. Of 281 randomized patients, 138 were treated with BF-200 ALA and 143 with MAL. Patients received two PDT sessions 1 week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J cm(-2)). The results shown include clinical end points and patients' reassessment 12 months after the last PDT. The study was registered with EudraCT (number 2013-003241-42). Results: Of the BF-200 ALA-treated patients, 93 4% were complete responders compared with 91 8% in the MAL group. The difference of means was 1 6, with a one-sided 97 5% confidence interval of -6 5, establishing noninferiority (P 0001). The results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were 10%. Conclusion: sTreatment of nonaggressive BCC with BF-200 ALA-PDT is highly effective and well tolerated with proven noninferiority to MAL-PDT. It demonstrates low recurrence rates after 1 year of follow-up. What's already known about this topic? Photodynamic therapy (PDT) using BF-200 aminolaevulinic acid (ALA) gel is registered and highly effective in the treatment of mild-to-moderate actinic keratosis and field cancerization. BF-200 ALA gel was recently approved for the treatment of superficial and/or nodular basal cell carcinoma (BCC) unsuitable for surgical treatment. PDT using methyl aminolaevulinate (MAL) cream is approved for the treatment of thin or nonhyperkeratotic and nonpigmented actinic keratoses, Bowen disease, and superficial and nodular BCCs when other therapies are considered less appropriate. What does this study add? BF-200 ALA-PDT is confirmed to be significantly noninferior to MAL-PDT for the treatment of nonaggressive BCC. Treatment-emergent adverse events were comparable between the two patient groups, with similar or slightly lower recurrence rates for BF-200 ALA gel compared with MAL cream after 12 months.

Background: Early detection of various types of nonmelanoma skin cancer has been a challenge in dermatology. Noninvasive examination procedures such as optical coherence tomography (OCT) play an increasingly important role, besides the established gold standard of histological tissue sample analysis. OCT is a noninvasive, cross-sectional, real-time technique that allows conclusions to be drawn with regard to the presence of pathologies. Objective: The objective of this study was to investigate whether it is possible to distinguish between different types of nonmelanoma skin cancer using OCT or not. Methods: A study population of a total of 25 cases, comprising 5 cases, each, of 5 tumor entities (i.e., basal cell carcinoma, superficial basal cell carcinoma, actinic keratosis, squamous cell carcinoma, and Bowen disease) was examined. Relevant lesions were scanned both centrally and peripherally in the multislice mode. All OCT images were blinded, randomized, analyzed, and evaluated by 2 clinicians experienced in OCT. Results: This study demonstrated that it is possible to determine correlations between various types of tumors and recurring tumor characteristics. Conclusion: This study showed that it is possible to distinguish between the different nonmelanoma skin cancers by using OCT, but further prospective studies have to be conducted to validate the sensitivity and specificity of the criteria.

BACKGROUND Malignant melanoma is an aggressive skin cancer, which can lead to metastasis development. Vascularization enhancement is fundamental for tumor growth, worsening the prognosis. Dynamic optical coherence tomography (D-OCT) enables the in vivo evaluation of vascular patterns in skin lesions. OBJECTIVE In vivo evaluation of the melanoma vessel morphology by means of D-OCT and correlation with Breslow index. METHODS Retrospective analysis of histologically proven melanomas, evaluated by D-OCT at three different depths (150, 300 and 500 μm), was performed. Vessels were classified according to morphology (dots, blobs, coiled, line, curved, serpiginous), distribution (regular, irregular) and the presence/type of branches. The data were correlated with Breslow thickness. RESULTS A total of 127 melanomas were evaluated. Dotted vessels were recorded at all depths, and their irregular distribution was associated with lesions thicker than 1.0 mm (from 75% to 91%), compared with thin ones (42%) at 150 μm (P = 0.031), and from 33% to 57% vs 18% at 300 μm (P = 0.021). Serpiginous and branching vessels with bulges were predominantly seen in melanomas thicker than 2 mm at 150 μm (from 14% to 27%, P

Background Multi-beam optical coherence tomography (OCT) is a novel method of non-invasive skin imaging allowing the evaluation of tissue at high level of lateral and axial resolution. It permits the horizontal and vertical evaluation of the extent of diseases. Objective Herein, we aimed to validate diagnosing basal cell carcinoma (BCC) by OCT using a newly developed scoring system (‘Berlin Score’-BS). This was based on the predetermined criteria such as dark border underneath the tumour and ovoid structures. Their frequency and distribution in subtypes of BCC were evaluated. Methods The study was conducted in two phases, in which the experience of examiner differed. A total of 127 BCC and 50 other skin diseases were examined. In phase one, students performed the evaluation of skin lesions using the BS, while in phase two an expert performed the scoring in a different subset of patients. Results Application of BS by students revealed sensitivity and specificity of 92.8% (95% CI 85.4–96.8) and 24.1% (95% CI 11.0–43.4) when reaching the lower threshold BS≥8. The most common BCC subtypes were superficial (28.7%) and nodular (22.6%) BCC. Second phase was carried out to verify collected data by a dermatological specialist and expert in using OCT. Increased sensitivity and specificity for OCT amounted to 96.6% (95% CI 80.4–99.8) and 75.2% (95% CI 52.5–90.9). Thereby 88% of all diagnoses were correctly classified confirmed by histopathology. Conclusion Multi-beam optical coherence tomography revealed to be a fast and promising device for assessing lesions by means of BS. Both students, who benefit from practice in handling OCT, and experts are able to perform this procedure. However, experience and training in the interpretation markedly increased sensitivity and specificity of the BS in our study. Moreover, redefinition and refining of the criteria seems necessary and may further increase the diagnostic value of OCT for NMSC.

Actinic keratosis (AK), a frequently diagnosed cutaneous neoplasm in individuals with chronic sun exposure or fair skin, is a risk factor for squamous cell carcinoma. AK presents as clinically visible lesions and/or as subclinical lesions where an entire field of area (field cancerization) contains lesions of various grades. The diagnosis and surveillance of subclinical AK is challenging. We report a new AK management approach, including subclinical AK, with noninvasive in vivo reflectance confocal microscopy (RCM) monitoring of field-directed topical 5-fluorouracil 0.5%/salicylic acid 10.0% (5-FU/SA; currently approved for single lesions). In this case series, eight patients with primarily recurrent, multiple AKs received ≤6 weeks of field-directed 5-FU/SA; complete clearance of clinical/subclinical AKs on various body areas was shown in most patients using RCM. RCM facilitated the detection/characterization of subclinical AKs in the setting of field cancerization. Topical field-directed 5-FU/SA monitored with RCM is a promising management approach for subclinical AKs.

The subtype of basal cell carcinoma (BCC) influences the choice of treatment. Optical coherence tomography (OCT) is a non-invasive imaging tool, and a recent development of an angiographic version of OCT has extended the application of OCT to image the cutaneous microvasculature (so-called dynamic OCT, D-OCT). This study explores D-OCT's ability to differentiate the common BCC subtypes by microvascular and structural imaging. Eighty-one patients with 98 BCC lesions, consisting of three subtypes: 27 superficial BCC (sBCC), 55 nodular BCC (nBCC) and 16 infiltrative BCC (iBCC) were D-OCT scanned at three European dermatology centres. Blinded evaluations of microvascular and structural features were performed, followed by extensive statistical analysis of risk ratio (RR) and multiple correspondence analysis. nBCC lesions displayed most characteristic structural and vascular features. Serpiginous vessels, branching vessels, vessels creating a circumscribed figure and sharply demarcated hyporeflective ovoid structures in the dermis were all associated with a higher risk of the subtype being nBCC. The presence of highly present lines and dark peripheral borders at the margin of ovoid structures was negatively associated with iBCC. Lastly, the finding of hyporeflective ovoid structures protruding from epidermis correlated with sBCC. We identified various microvascular and structural D-OCT features that may aid non-invasive identification of BCC subtypes. This would allow clinicians to individualize and optimize BCC treatment as well as aid follow-up of non-surgical treatment.

Background: In vivo reflectance confocal microscopy (RCM) is a promising non-invasive skin imaging technique that could facilitate early diagnosis of basal cell carcinoma (BCC) instead of routine punch biopsies. However, the clinical value and utility of RCM vs. a punch biopsy in diagnosing and subtyping BCC is unknown. Objective: To assess diagnostic accuracy of RCM vs. punch biopsy for diagnosing and subtyping clinically suspected primary BCC. Methods: A prospective, consecutive cohort of 100 patients with clinically suspected BCC were included at two tertiary hospitals in Amsterdam, the Netherlands, between 3 February 2015 and 2 October 2015. Patients were randomized between two test-treatment pathways: diagnosing and subtyping using RCM imaging followed by direct surgical excision (RCM one-stop-shop) or planned excision based upon the histological diagnosis and subtype of punch biopsy (standard care). The primary outcome was the agreement between the index tests (RCM vs. punch biopsy) and reference standard (excision specimen) in correctly diagnosing BCC. The secondary outcome was the agreement between the index tests and reference standard in correctly identifying the most aggressive BCC subtypes. Results: Sensitivity to detect BCC was similar for RCM and punch biopsy (100% vs. 93.94%), but a punch biopsy was more specific than RCM (79% vs. 38%). RCM expert evaluation for diagnosing BCC had a sensitivity of 100% and a specificity of 75%. The agreement between RCM and excision specimen in identifying the most aggressive BCC subtype ranged from 50% to 85% vs. 77% by a punch biopsy. Conclusion: Reflectance confocal microscopy and punch biopsy have comparable diagnostic accuracy to diagnose and subtype BCC depending on RCM experience. Although experienced RCM users could accurately diagnose BCC at a distance, we found an important difference in subtyping BCC. Future RCM studies need to focus on diagnostic accuracy, reliability and specific criteria to improve BCC subtype differentiation.

Background A clear distinction between actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) cannot reliably be made by clinical and dermoscopic evaluation alone. Dynamic optical coherence tomography (D-OCT) is a novel angiographic variant of OCT that allows for non-invasive, in vivo evaluation of the cutaneous microvascular morphology. Objective To investigate the microvascular structures of AK, BD and invasive SCC using D-OCT in order to gain insights into the microvascular morphology of lesions in the spectrum of keratinocyte skin cancers. Methods Forty-seven patients with a total of 54 lesions (18 AK, 12 BD and 24 SCC) were included in the study. D-OCT still images of AK, BD and SCC at three predefined skin depths were prepared and randomized, creating a study set of 162 D-OCT images. Three observers performed blinded evaluations of the randomized study set assessing multiple parameters including the different types of vascular morphology. Non-blinded quantitative measurements of vascular diameter were also performed. Results The blinded observer analysis suggests that D-OCT evaluation of the vascular morphology may aid in distinguishing AK, BD and SCC lesions. We identified two vascular shapes that presented significantly differently across the lesion types, namely 'blobs' and 'curves'. A strong presence of blobs at 300 μm skin depth was characteristically seen in a third of BD cases, while not or only slightly present in AK and SCC lesions. Vascular curves were predominantly present in AK lesions. Conclusion We identified various vascular D-OCT features that may aid in non-invasively differentiating subtypes within the keratinocyte skin cancer spectrum.

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SummaryBackground To date, studies with ingenol mebutate gel have used clinical clearance, not histological clearance, as a primary efficacy endpoint. Objectives This phase 1, multicentre, single-arm, open-label study sought to histologically confirm clinical clearance of actinic keratoses (AKs) to support a treatment effect deep in the epidermis. Methods Patients (n = 108) aged ≥18 years with histologically confirmed AK within a 25-cm2 contiguous treatment area on the trunk and extremities received ingenol mebutate 0.05% gel for 2 consecutive days and were followed up on day 3 and week 8. One AK was randomly pre-selected at day 1 for clinical and histological evaluation at week 8; and for reflectance confocal microscopy (RCM) in a subset of patients. Primary endpoint was clinical and histological clearance of AKs at week 8. Results The observed agreement rate between clinical and histological assessments of clearance of a single AK was 81.9% and the positive predictive value of a clinical assessment of clearance was 87%. Agreement between the two pathologists was 88%. The common composite 8-week complete clearance rate was 41% (95% confidence interval 32%, 50%). Observed agreement rates between RCM and pathologist I and II assessments of clearance were 72.9% and 81.4%, respectively. Thirty patients (27.8%) experienced 38 adverse events (AEs). Application-site pain (four patients, 3.7%) was the most common treatment-related AE inside the treatment area. Conclusion Ingenol mebutate achieves histopathological clearance of AKs that correlates with observed clinical clearance. Clinical clearance is a good predictor for histological clearance. This article is protected by copyright. All rights reserved.

Dynamic optical coherence tomography (D-OCT) is an angiographic variation of OCT that non-invasively provides images of the in vivo microvasculature of the skin by combining conventional OCT images with flow data. The objective of this study was to investigate and report on the D-OCT technique for imaging of the vascular networks in skin as well as to validate the method by comparing the results against already accepted blood flow measuring tools.35 healthy subjects were recruited for the multicentre study, consisting of three experiments set up to examine the vascular blood perfusion during different induced physiologic changes in the blood flow. In order to validate the D-OCT images against existing techniques for blood flow measuring we performed consecutive D-OCT, chromametry and laser speckle contrast imager (LSCI) measurements on identical skin sites in all of the experiments. Blinded observer evaluations were performed in order to evaluate the vascular morphology in the D-OCT images.The results showed a statistically significant positive correlation between the D-OCT measurements and the LCSI flux measurements (rs=0.494; 95% CI [0.357, 0.615]; p0.001), and also the redness a* measurements were positively correlated with the D-OCT measurements (r=0.48; 95% CI [0.406, 0.55]). D-OCT was able to reliably image and identify morphologic changes in the vascular network consistent with the induced physiological changes of blood flow.This study has initiated validation of the use of D-OCT for imaging of skin blood flow. Our results showed that D-OCT was able to reliably image and identify changes in the skin vasculature consistent with the induced physiological blood flow changes. These basic findings support the use of D-OCT imaging for in vivo microcirculation imaging of the skin.

Optical coherence tomography (OCT) represents a non-invasive imaging technology, which may be applied to the diagnosis of non-melanoma skin cancer and which has recently been shown to improve the diagnostic accuracy of basal cell carcinoma. Technical developments of OCT continue to expand the applicability of OCT for different neoplastic and inflammatory skin diseases. Of these, dynamic OCT (D-OCT) based on speckle variance OCT is of special interest as it allows the in vivo evaluation of blood vessels and their distribution within specific lesions, providing additional functional information and consequently greater density of data. In an effort to assess the potential of D-OCT for future scientific and clinical studies, we have therefore reviewed the literature and preliminary unpublished data on the visualization of the microvasculature using D-OCT. Information on D-OCT in skin cancers including melanoma, as well as in a variety of other skin diseases, is presented in an atlas. Possible diagnostic features are suggested, although these require additional validation.

Summary Background There are poorly documented variations in the journey a skin cancer patient will follow from diagnosis to treatment in the European Union. Objectives To investigate the possible difficulties or obstacles that a person with a skin malignancy in the European Union may have to overcome in order to receive adequate medical screening and care for his/her condition. In addition, we wished to explore differences in European health systems, which may lead to health inequalities and health inequities within Europe. Methods Ten European countries took part in this investigation (in alphabetical order): Finland, Germany, Greece, Italy, Malta, Poland, Romania, Spain, the Netherlands and the U.K. The individual participants undertook local and national enquiries within their own country and completed a questionnaire. Results This exercise has identified important differences in the management of a skin cancer patient, reflecting major disparities in health care between European countries. Conclusions Further investigation of health disparities and efforts to address health inequalities should lead to improvements in European health care quality and reduction in morbidity from skin cancer.

Background There are limited data regarding the association of actinic keratosis (AK) and other types of nonmelanoma skin cancer (NMSC); studies investigating possible correlation of AK with melanocytic naevi are even scarcer. To our knowledge, there are no data examining the risk of AK in people using specific medications. Objective To investigate constitutional and exposure risk factors leading to AK and the coexistence of AK with NMSC and melanoma. Methods A multicentre hospital-based case-control study was performed in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain, including 343 patients with actinic keratosis (AK), 409 with squamous cell carcinoma (SCC), 602 with basal cell carcinoma (BCC), 360 with invasive melanoma and 119 with in situ melanoma, and 686 control subjects. Exposures were assessed by questionnaires that were partly self-administered and partly filled out by dermatologists. Unconditional logistic regression modelling was used to assess associations including the influence of phenotypic characteristics, presence of naevi, sun-exposure habits and certain drugs on AK risk. Results Differences in hair and eye coloration variably influenced the risk for AK, with red hair signifying a seven times higher risk [odds ratio (OR) 6·9, 95% confidence interval (CI) 4·34-11·00), and brown - compared with blue - eyes, about a 40% reduced risk (OR 0·61, 95% CI 0·13-0·92). The darker the skin phototype, the lower the risk for AK, with phototype IV exhibiting nine times less risk of developing AK. Some and many freckles on the arms were associated with an OR of 1·8 (95% CI 1·08-2·81) and 3·0 (95% CI 1·10-3·54), respectively, while overall number of naevi and high educational level were inversely associated with AK. Sun exposure, thiazide diuretics and cardiac drugs had a higher risk for AK. SCC was the most frequent (58%) skin neoplasm coexisting with AKs, followed by BCC (30%), melanoma in situ (12%) and invasive melanoma (6%). Conclusion In this large case-control study from across Europe the expected associations were confirmed for known risk factors. Some possible new risk factors, including cardiac and diuretic drugs, were identified, creating a new field for further investigation in future studies.

Summary Background During recent years numerous studies have suggested that personal and environmental factors might influence cancer development. Objectives To investigate environmental and personal characteristics associated with skin cancer risk. Methods A multicentre hospital-based case–control study was performed in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain, including 409 patients with squamous cell carcinoma (SCC), 602 with basal cell carcinoma (BCC) and 360 with cutaneous malignant melanoma (CMM) and 1550 control persons. Exposures were assessed by questionnaires that were partly self-administered, partly completed by dermatologists. Unconditional logistic regression modelling was used to assess associations including the influence of certain drugs and food items on skin cancer risk. Results The usual associations were observed for sun exposure and pigmentation characteristics, with chronic sun exposure being most strongly associated with SCC risk, and naevi and atypical naevi with CMM risk. Use of ciprofloxacin was associated with a decreased risk of BCC [odds ratio (OR) 0·33] and use of thiazide diuretics was associated with an increased risk of SCC (OR 1·66). Ciprofloxacin was also associated with SCC (OR 0·34) and thiazines with BCC (OR 2·04), but these associations lost significance after correction for multiple testing. Consumption of pomegranate, rich in antioxidants, was associated with decreased BCC and SCC risk, also after correcting for multiple testing. Recent experience of stressful events was associated with increased risk, particularly of CMM. Conclusions In this large case–control study from across Europe the expected associations were observed for known risk factors. Some new potential protective factors and potential risk factors were identified for consumption of certain food items, medication use and stress, which deserve further investigation in future studies.

Summary Background A wide variety of both surgical and nonsurgical therapies is currently available for patients with skin cancer. Objectives This part of the EPIDERM (European Prevention Initiative for Dermatological Malignancies) project is aimed at the evaluation of the treatment preferences for skin cancer in eight countries of the European Union. Methods A multicentre hospital-based case–control study was carried out at dermatology departments in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain. Patients with skin cancer (basal cell carcinoma, actinic keratosis, squamous cell carcinoma, cutaneous malignant melanoma and Bowen disease) were consecutively enrolled between July 2008 and July 2010. Information on the study variables (sex, age, country, tumour type, anatomical location and treatment) was obtained from questionnaires designed by the EPIDERM project. Results In total, 1708 patients with skin cancer were included. Surgery was the first treatment option in 76·5% of the patients (P = 0·001). Actinic keratosis was the only tumour type in which nonsurgical treatment was more frequent than surgery (91·4%). Tumours on the head were less likely to be surgically excised than those at other locations (odds ratio 0·25, P = 0·001). Simple excision or curettage was the most common surgical procedure (65·4%), followed by graft and flaps (22·4%). Cryotherapy was the most common nonsurgical option (52·4%), followed by imiquimod (18·0%), photodynamic therapy (PDT; 12·0%), 5-fluorouracil (5-FU; 5·7%), and diclofenac with hyaluronic acid (4·0%). Conclusions Surgery remains the first-choice treatment of skin cancer. Regarding nonsurgical treatments, the conservative treatments available (imiquimod, 5-FU, PDT and diclofenac gel) have not yet exceeded the use of ablative options such as cryotherapy despite their accepted benefit of treating field cancerization.

Background Actinic cheilitis (AC) represents the equivalent of actinic keratosis on the lip. Various treatment modalities are available and the efficacy of diclofenac in hyaluronic acid has recently been described. Reflectance confocal microscopy (RCM) is a non-invasive imaging technique which has recently been applied for the diagnosis of actinic keratoses. Herein, we describe the applicability of RCM for the diagnosis of AC and for monitoring of treatment response of AC to diclofenac in hyaluronic acid. Methods Ten Caucasian patients with clinical suspicion for AC were included in this study. To obtain a non-invasive diagnosis, RCM was performed at baseline, followed by biopsy and respective confocal-histopathological correlation. Six patients with a histological diagnosis of AC were treated with diclofenac in hyaluronic acid, whereby monitoring was performed by RCM. Results Reflectance confocal microscopy was able to correctly identify 6/7 cases of AC and 3/3 cases of benign lesions. The most important RCM criteria for diagnosis of AC were cellular atypia at the stratum spinosum and granulosum with atypical honeycomb pattern. One patient with AC was misclassified as inflammatory cheilitis by RCM as it showed marked inflammatory response and lacked clear signs of cellular atypia on RCM imaging. Following topical treatment with diclofenac gel, 5/6 patients (83%) showed a good treatment response with regression of dysplasia on consecutive RCM examination. Conclusions Reflectance confocal microscopy is a promising tool for the non-invasive diagnosis and monitoring of actinic cheilitis. However, marked inflammation represents a potential diagnostic pitfall. In this regard, biopsy should be performed in doubtful cases.

Reflectance confocal microscopy (RCM) is a novel, noninvasive imaging technique based on the collection of in vivo high-resolution images using the differential reflectance of the subcellular structures of the epidermis and dermis when illuminated with a coherent light source. RCM has been used to visualize different skin pathologies, notably actinic keratoses and several types of skin cancer, including squamous and basal cell carcinomas and melanoma. Basal cell carcinoma is particularly amenable to examination by RCM, and its clinical features as visualized by this technique have been described in detail. In addition, RCM allows follow-up of the response of diseased skin to treatment and aids in the determination of the precision of surgical procedures due to the possibility of performing repetitive examinations without further damage of the affected area.

Background: Antibiotic therapy is thought to improve lung function in patients with cystic fibrosis (CF) by decreasing neutrophil-derived inflammation. We investigated the origin and clinical significance of lactate in the chronically inflamed CF lung. Methods: Lactate was measured in sputa of 18 exacerbated and 25 stable CF patients via spectrophotometry and gaschromatography. Lung function was assessed via spirometry. Seven patients with chronic obstructive pulmonary disease (COPD) and three patients with acute lung inflammation served as control groups. Neutrophil and bacterial lactate production was assessed under aerobic and anaerobic conditions. Results: In sputum specimens of patients with respiratory exacerbations lactate concentrations decreased significantly (pb0.005) from 3.4±2.3 mmol/L to 1.4±1.4 mmol/L after 2–3 weeks of intravenous antibiotics. Successful treatment was reflected in 16 patients (88.9%) by FVC increase associated with lactate decrease (pb0.05). In every single sputum lactate was detectable (3.0±3.1 mmol/L, range 0.2–14.1 mmol/L). Lactate was lower (1.6±0.8 mmol/L) in sputa from seven COPD patients, and it was below the detection limit in three patients with acute lung inflammation. Neutrophil lactate production accumulated up to 10.5 mmol/L after 4 days, whereas bacterial lactate production didnot appear to contribute substantiallytosputum lactateconcentrations. Conclusions: Successful antibiotic therapy is reflected by a decrease in lactate concentrations. Neutrophils are the most likely source for lactate in sputum of CF patients. Therefore lactate may be used to monitor responses to antibiotic therapy as an adjunct to lung function measurements.

Background We previously described the principal results from an observational, prospective, multicentre, clinical trial of the diagnostic value of optical coherence tomography (OCT) for basal cell carcinoma (BCC) in a clinical setting. In this trial, much additional useful information was gathered that warranted further analysis, presented here. Objectives To investigate the influence of candidate diagnostic criteria, OCT image quality, lesion location, and observer confidence and interobserver variability on the diagnostic performance of OCT, and to assess its potential use for diagnosis of BCC subtypes. Methods A total of 234 clinically unclear 'pink lesions' were evaluated in three steps: after clinical examination, after adding dermoscopy and after adding OCT. In addition to the diagnoses (including lesion subtype), observers recorded which of 15 diagnostic criteria the OCT image contained, their confidence in the diagnoses, the OCT image quality and the anatomical location of the lesion. Results Diagnostic performance of OCT did not depend on the lesion's anatomical location. Good OCT image quality was correlated with improved diagnostic performance, but diagnostic performance for lesions with mediocre image quality was still better than by clinical and dermoscopic examination. The main reason for reduced image quality was superficial scales and crusting. Observer confidence in diagnosis was correlated with diagnostic performance. Interobserver diagnostic performance was consistently higher than clinical examination and dermoscopy across all sites. BCC subtype could be determined with moderate accuracy, but further independent image markers are required. Conclusion OCT is useful in the diagnosis of BCC.

BackgroundIn infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release and ceramide accumulation. We sought to investigate CF lung inflammation in the alveoli.MethodsLung tissue from 14 CF patients and four healthy individuals was analyzed for numbers of effector cells, elastin and collagen concentrations, inflammatory markers and density of Pseudomonas aeruginosa. Additionally, desmosine and isodesmosine concentrations were determined in 52 urine specimens from CF patients to estimate the burden of elastase activities in respiratory secretions.ResultsElastin concentration was significantly decreased and collagen significantly increased in CF alveolar tissues as compared to age-matched, healthy individuals. Elastin split products were significantly increased in urine samples from patients with CF and correlated inversely with age, indicating local tissue remodelling due to elastin degradation by unopposed proteolytic enzymes. Alveolar inflammation was also characterized by a significant cell infiltration of neutrophils, macrophages and T cells, extensive nuclear factor-κB and insulin-like growth factor-1 activation in various cell types and increased intercellular adhesion molecule-1 expression, and increased numbers of myofibroblasts. Additionally, ceramide accumulated in type II alveolar epithelial cells, lacking CFTR. P. aeruginosa organisms were rarely present in inflamed alveoli.ConclusionsChronic inflammation and remodeling is present in alveolar tissues of the CF lung and needs to be addressed by anti-inflammatory therapies.

Non-melanoma skin cancer (NMSC) represents the most common cutaneous neoplasms and, in the past decade, nonsurgical treatment modalities have been established as part of the management of NMSC. Recently, novel noninvasive diagnostic modalities have been developed and, of these, reflectance confocal microscopy (RCM) offers imaging of the skin in vivo with cellular resolution. NMSCs, including basal cell carcinoma, actinic keratosis and squamous cell carcinoma, have been evaluated by RCM, and diagnostic criteria were defined. By correlation with routine histology sections and in comparison with normal skin, RCM showed high sensitivity and specificity values. RCM allows the noninvasive evaluation of a variety of skin conditions, including NMSC. RCM may aid in the diagnosis and differential diagnosis of NMSC, as well as in monitoring of treatment response to topical treatment modalities. Therefore, RCM appears to be a promising diagnostic tool with many possible applications in dermatology.

BACKGROUND In vivo reflectance confocal microscopy (RCM) has been used for evaluation of the morphologic features of nonmelanoma skin cancer. The application of RCM for diagnosis of basal cell carcinoma has been reported; however, the evaluation of actinic keratoses (AKs) has only been the subject of preliminary studies. STUDY GOAL The goal of this study was to evaluate the applicability of RCM in the diagnosis of AK in correlation with routine histology. MATERIALS AND METHODS Forty-four Caucasians with a minimum of one AK participated in this study. Evaluation consisted of clinical examination, RCM, and routine histology, including a total of 46 AKs in the final analysis. Ten normal skin sites served as controls. RCM features of AK included parakeratosis, architectural disarray, and keratinocyte pleomorphism. Following blinded evaluations, sensitivity/specificity, kappa analysis, and Spearman's correlation were performed on all parameters. RESULTS Sensitivity/specificity values of RCM features ranged from 80% to 98.6%. The presence of architectural disarray and cellular pleomorphism appeared to be the best predictor of AK. CONCLUSION In summary, RCM may be a promising technology for the noninvasive detection of AK and as adjunct tool to clinical diagnosis and monitoring. However, the preliminary nature of this study warrants further investigations.

Summary Background Actinic keratoses (AK) frequently occur on sun-exposed skin and are considered as in situ squamous cell carcinoma. To date, no treatment algorithm exists for first or second line therapies due to the lack of comparative studies. Objective This study compared the initial and 12-month clinical clearance, histological clearance, and cosmetic outcomes of topically applied 5% imiquimod (IMIQ) cream, 5% 5-fluorouracil (5-FU) ointment and cryosurgery for the treatment of AK. Patients/methods Patients were randomised to one of the following three treatment groups: one or two courses of cryosurgery (20–40 s per lesion), topical 5-FU (twice daily for 4 weeks), or one or two courses of topical imquimod (three times per week for 4 weeks each). Results Sixty-eight per cent (17/25) of patients treated with cryosurgery, 96% (23/24) of patients treated with 5-FU, and 85% (22/26) of patients treated with IMIQ achieved initial clinical clearance, p = 0·03. The histological clearance rate for cryosurgery was 32% (8/25), 67% (16/24) for 5-FU, and 73% (19/26) in the IMIQ group, p = 0·03. The 12-month follow-up showed a high rate of recurrent and new lesions in the 5-FU and cryosurgery arms. The sustained clearance rate of initially cleared individual lesions was 28% (7/25) for cryosurgery, 54% (13/24) for 5-FU and 73% (19/26) for IMIQ (p

Summary Background Clinical differentiation between actinic keratosis (AK) and disseminated superficial actinic porokeratosis (DSAP) may pose a significant challenge, and histological evaluation is often also required for diagnosis. Distinct morphological features can be distinguished upon histopathological examination, but the use of non-invasive tools, such as reflectance confocal microscopy (RCM), may be an eligible alternative for confirmation of diagnosis. Objectives The aim of this study was to determine the relevant RCM criteria for the identification of disseminated superficial actinic porokeratoses (DSAPs) and to define distinguishing criteria for DSAPs compared with actinic keratosis (AKs). Patients/methods A total of 20 patients with a clinical diagnosis of AK or DSAP were included in this study. All lesions were evaluated by clinical examination, and RCM and one clinically identified lesion was biopsied for histological confirmation. Results Cellular and nuclear atypia, inflammation, spongiosis, parakeratosis and changes in epidermal architecture were present in both lesion types (i.e. AKs and DSAPs). However, these features were more pronounced in AKs. Whereas AKs exhibited more disseminated parakeratotic changes, parakeratosis was found focally present on the border of DSAP lesions. Most characteristically, a distinct border corresponding to cornoid lamella in RCM can be identified in DSAPs. Conclusions Distinguishing features of DSAPs, such as cornoid lamella, sharp demarcation of the lesion and focal keratinocyte atypia are easily identifiable using RCM, and correlate well with histopathology. Whilst RCM has previously been used in the evaluation of AKs, it has not yet been used to investigate DSAPs. The findings in this study suggest the feasibility of non-invasive tools, such as RCM for the differentiation of AKs and DSAPs. However, further studies are warranted to assess the sensitivity and specificity of RCM in the diagnosis of DSAP.

Summary Background Actinic cheilitis is a frequent manifestation of actinic dysplasia and requires early therapy to prevent its progression into invasive squamous cell carcinoma (SCC). Several therapies are used, ranging from unspecific lesion-adapted destructive techniques (i.e. laser) to ambitious surgical field-management (vermillionectomy). There is increasing awareness of the effectiveness of field adapted, non destructive therapies, such as photodynamic therapy or 5% imiquimod. Diclofenac 3% gel is used in the treatment of actinic keratosis (AK), but it has not been evaluated for the treatment of actinic cheilitis. Objectives This non-blinded, uncontrolled case series study evaluated the effects of diclofenac 3% gel in the treatment of actinic cheilitis. Patients/methods Six patients with histologically verified actinic cheilitis were treated with diclofenac 3% gel, twice daily for 6 weeks. Clinical assessment was performed 2–4 weeks after the end of treatment. Results Four out of six patients showed clinical clearing of actinic cheilitis 2–4 weeks after the end of treatment. Biopsies were taken from the treated areas at the final visit to verify clinical clearance. Side effects in most of the patients included mild erythema and mild to moderate swelling of the lips. Conclusions Topical therapy with diclofenac 3% gel may be an efficient, cosmetically more appealing alternative treatment for actinic cheilitis than currently used destructive therapies. However, future studies and long-term follow-up of patients will be needed to compare its efficacy with established forms of therapy.

Background Brimonidine is a selective α2 adrenergic receptor agonist with potent vasoconstrictive activity topically used for treatment of facial flushing and erythema caused by rosacea. Direct evidence for the in vivo morphology changes in skin vessels induced by topical application of brimonidine is limited. Dynamic optical coherence tomography is a novel technology that combines conventional OCT with information on flow and thereby provides supplementary information about the microvasculature. Dynamic OCT is non-invasive and creates high-resolution in vivo images of skin to a depth of maximum 2 mm. Objective The objective of this study was to examine and describe micro-morphological skin vessel changes in normal skin exposed to brimonidine gel using Dynamic OCT. Materials and methods A total of 35 healthy subjects from three European clinical dermatology centres were included in the study. A normal skin area on the cheek was marked and clinically photographed. Brimonidine gel 0.33% was applied on the area and chromaticity measurements; laser speckle measurements and Dynamic OCT images were acquired at baseline and 60 min after application. The images were subsequently described in detail and quantitatively analysed. Results All the measurement tools (chromaticity, laser speckle, Dynamic OCT showed highly significant (P < 0.001) quantitative differences in blood flow before and after the application of brimonidine. In 58% of the subjects the Dynamic OCT images showed notable changes in the morphology of the blood vessel network after application of brimonidine including a marked reduction in the abundance and the diameter of the blood vessels. Conclusion The vascular constriction induced by topical brimonidine gel 0.33% was visualized in vivo by Dynamic OCT and confirmed by quantitative measurements and analyses. This study shows that Dynamic OCT can detect characteristic morphological changes in the vessels and may potentially aid the monitoring of treatment effects on skin vessels following topical or laser treatment.

Alterations of the skin microvasculature are known to play an important role in the development and maintenance of psoriatic skin lesions. In this study, we investigated lesional skin in 11 psoriatic patients during a modified Goeckerman treatment using reflectance confocal microscopy (RCM) to study the relationship between clinical clearance and histological normalization of psoriatic skin and the significance of histological abnormalities on the course of disease. The treatment regimen resulted in a significant reduction of the Psoriasis Area and Severity Index (PASI) as well as capillary and papillary diameters (p < 0.0001). The capillary and papillary diameters were still enlarged when compared to those in normal skin (p < 0.001). Capillary and papillary diameters correlated with each other prior to and after treatment (correlation coefficient = 0.63 and 0.64, p = 0.01 and 0.002, respectively) but not with the PASI. Capillary and papillary diameters after treatment and percentage reduction of the PASI during treatment seemed to be better predictors for the clinical course of relapse than the PASI after treatment. These findings make the subclinical changes of psoriatic skin vessels and dermal papillae a legitimate target for treatment. Further investigations of a large group of patients are needed to evaluate the potential of RCM findings as successor of the PASI in the monitoring of psoriasis.

SummaryBackground The diagnostic criteria for basal cell carcinoma (BCC) using optical coherence tomography (OCT) have been described previously, but the clinical value of these findings remains unknown. Objectives To investigate the diagnostic value of OCT for BCC in a typical clinical setting. The primary efficacy end point was a diagnosis of BCC for each lesion. Secondary end points were the diagnosis of other possible conditions. Methods This was an observational, prospective, multicentre study in which consecutive patients with nonpigmented pink lesions suspicious for BCC underwent clinical assessment, dermoscopy and OCT, with the diagnosis recorded at each stage. Once all diagnoses had been recorded, the histological results were disclosed. In total 164 patients with 256 lesions were recruited. Histology was missing for 21 lesions, leaving 235 lesions in 155 patients for analysis. Results Sixty per cent of lesions (141 of 235) were identified as BCC by histology. A slight increase of sensitivity was noted following OCT, which did not reach statistical significance. The specificity increased significantly from 28·6% by clinical assessment to 54·3% using dermoscopy and to 75·3% with the addition of OCT (P

Background: Actinic Keratosis (AK) is the clinical manifestation of cutaneous dysplasia of epidermal keratinocytes, withprogressive trend towards squamous cell carcinoma. Objective: To evaluate the strength of the correlation between keratinocyte atypia, as detected by Reflectance Confocal Microscopy (RCM) and histopathology, and to develop a more objective atypia grading scale for RCM quantification,through a discrete ranking. Methods: A total of 48 AKs and two control areas (photodamaged and non-photodamaged skin) were selected for this study. All these areas were documented by RCM and biopsied for histopathology. One representative image of the epidermis was selected for RCM and for histopathology and used for side-by-side comparison with purpose written soft-ware. The assessor chose which of two images displayed more keratinocyte atypia, and an ordered list from the imageshowing the least to the most keratinocyte atypia was generated. Three evaluations were obtained for RCM and two for histopathology. Results: Good interobserver correlation was obtained for RCM and histopathology grading, with high concordance between RCM and histopathology grading Conclusions: Expert rater scan consistently distinguish different grades of cytological atypia. Non-invasive RCM data from in vivo imaging can be graded for keratinocyte atypia, comparable to histopathological grading. Refereed/Peer-reviewed

Actinic keratosis (AK) is a common skin disease seen in daily practice. It is associated with a risk of progression to invasive squamous cell carcinoma and can be regarded as a marker of increased risk for non-melanoma skin cancer. The use of a field-directed treatment approach reflects the need to initiate early treatment over an affected area to prevent tumour development and local recurrence. Candidate field-directed treatments require a mechanism of action compatible with an effect on field cancerisation, immediate and long-term efficacy against visible lesions and efficacy against subclinical AK. Applicability to large treatment areas, tolerability compatible with long-term use, utility in organ transplant patients and, ideally, evidence of extended long-term activity may also be desirable. We review the evidence of a role for topical diclofenac sodium 3% administered in a 2.5% hyaluronic acid gel (diclofenac/HA) as field-directed treatment. Diclofenac/HA directly targets AK pathophysiology through multiple mechanisms, including induction of apoptosis, inhibition of angiogenesis and reduced inflammation. Clearance of visible field cancerisation is safely and rapidly achieved with a 90-day treatment course in patients with affected areas of up to 50 cm(2) and is associated with a ≥75% reduction in target lesion number score in 85% and 91% of patients, respectively, at 30 days and 1 year post-treatment. Following treatment of AK in high-risk transplant patients, 45% remained free of lesions in the treatment area at 2 years post-treatment. We conclude that diclofenac/HA fulfils most criteria necessary to be considered an appropriate candidate for a field-directed treatment in AK.

Background/Aims Herein, we report a case of microcystic adnexal carcinoma (MAC), which we correlated and evaluated by optical coherence tomography (OCT) and conventional H&E histology. Methods A commercially available OCT scanner was used for imaging. Several multi-slice images were obtained from the central portion of the lesion. Correlation of OCT findings with histology was performed retrospectively. Results Microcystic adnexal carcinoma showed characteristic criteria, which were divided into superficial and sub-epidermal findings. Conclusion The use of OCT can visualize characteristic criteria of MAC, thus enabling prompt diagnosis before surgery.

Minimally invasive diagnostic tools have received increased attention for diagnosis, screening and management of nonmelanoma skin cancer (NMSC). Several modalities are commercially available, including high frequency ultrasound, optical coherence tomography and confocal microscopy. While systematic clinical analyses are often lacking, recent reports have shown promising results for reflectance confocal microscopy (RCM) for diagnosis of actinic keratoses and basal cell carcinoma.

Summary Background Non-melanoma skin cancer (NMSC) represents a significant cause of morbidity in organ transplant patients; the relative risk of squamous cell carcinoma and actinic keratosis (AK) is 100 and 250 times higher, respectively, compared with immunocompetent patients. Objectives The aim of this study was to investigate the effects of 3% diclofenac gel on the clearance rates of multiple AKs in organ transplant recipients (OTRs). Patients/methods An open-label study was conducted in six patients (three kidney, one liver and two heart transplant patients) with histories of multiple NMSCs and extensive actinic keratoses (AKs). Patients were treated with diclofenac 3% gel, twice daily for 16 weeks. Complete and partial clearance rates of AKs were assessed after 16 weeks and biopsies were performed 4 weeks post-therapy on clinically typical AKs identified prior to the start of treatment. Results Three out of six patients showed complete clinical and histological clearance after 16 weeks of treatment with diclofenac 3% gel. Two further patients showed a marked (≥ 75% lesion reduction) improvement in their overall AK lesion count in the treatment area. One patient showed a 30% lesion reduction in the area treated. Local adverse events at the site of application were very mild and included mild erythema and marginal erosion. No systemic side effects were reported. Conclusions Results suggest that diclofenac 3% gel may be useful in the treatment and control of multiple AK lesions in OTRs. Further studies are needed to investigate the efficacy and safety of this therapy for the local treatment of AK in greater numbers of immunosuppressed patients.

The skin is not only the largest organ of the human body but also represents a barrier to the environment, protecting our body from water loss, penetration of environmental pollutants and microorganisms [1–3]. The skin has also a social function, as people frequently associate success in their private and professional lives with young-looking, smooth skin [4]. Therefore, not only medical but also cosmetic aspects are to be considered in skin treatment. While topically applied medical products must penetrate through the skin barrier in order to become effective in the living cells, cosmetic products do not necessarily induce any medical effects [5]. In most cases, these products remain on the skin surface or in the upper corneal layers in order to protect the skin (e.g., sunscreens) or to stabilise the dermal barrier (e.g., skin protection creams or lotions). Sometimes, in particular with respect to anti-aging creams, it is difficult to distinguish medical from cosmetic products.