Actinic Keratosis Lesions Research Articles

Liquid nitrogen cryotherapy effectively and safely improves response of thick Actinic Keratoses lesions by 5-aminolevulinic acid-based photodynamic therapy: a randomized, prospective, single-blind trial

BackgroundActinic keratoses (AK) may progress into squamous cell carcinoma. Many combination therapies were used to improve the clearance rate. However, there are limited studies on the efficacy and safety of lesion-directed Liquid nitrogen cryotherapy combined with field-directed photodynamic therapy (PDT). ObjectiveThis study is aimed to determine the efficacy and safety of Liquid nitrogen cryotherapy combined with PDT in Chinese patients with actinic keratosis. MethodsA total of 61 patients with AK were selected at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College between August 2018 and August 2023. They were randomly divided into PDT plus Liquid nitrogen cryotherapy group(LN-PDT)and control PDT group(C-PDT)with 30 patients and 31 patients, respectively. 27 patients in the LN-PDT group and 28 patients in the C-PDT group completed the clinical sessions. Efficacy, adverse effects, and cosmetic outcomes were recorded and compared between the two groups. Results3 months after the final treatment, the clearance rates for total AK lesions were 97.4%(449/461) in the LN-PDT group and 93.4%(456/488)in the C-PDT group (P < 0.05). For grade I AK lesions, the clearance rates were 99.2% (234/237) for the LN-PDT group and 98.3% (237/241) for the C-PDT group (P >0.05). For grade II lesions, the clearance rates were 97.5% (156/160) for the LN-PDT group and 91.9% (172/186) for the CPDT group (P < 0.05). For grade III lesions, the clearance rates of the LN-PDT and C-PDT groups were 87.5% (58/64) and 78.7% (47/61), respectively (P < 0.05). The two groups had no significant differences in pain, erythema, edema, hyperpigmentation and scarring. Cosmetic outcomes mainly were excellent or good in both groups with no significant difference. ConclusionLiquid nitrogen cryotherapy combined with PDT showed higher efficacy on grade II and grade III AK lesions than PDT alone. The two groups have similar adverse effects and cosmetic outcomes.

Tirbanibulin as a Novel Treatment in Actinic Keratosis: A Literature Review

Introduction and purpose: Actinic keratosis (AK) is a common dermatological condition that primarily affects fair-skinned individuals due to cumulative ultraviolet light exposure, potentially leading to squamous cell carcinoma (SCC). AK therapy is divided into two main branches: lesion-directed therapy (cryotherapy, lasers, and surgical methods) and field cancerization-directed therapy (photodynamic therapy and topical agents). Unfortunately, the occurrence of local skin reactions (LSRs) and the therapy duration counted in weeks disrupt patient compliance. This study aims to review the clinical trials concerning the efficacy, safety, and adverse effects of tirbanibulin, a novel promising treatment for AK, which led to its approval and therapeutic development. Materials and methods: Literature available in PubMed and GoogleScholar databases were reviewed using the following keywords: actinic keratosis; actinic keratosis treatment; tirbanibulin. Results: Tirbanibulin's mechanism involves inducing apoptosis by inhibiting microtubule polymerization, which distinguishes it from other treatments that often cause significant inflammation. Clinical trials demonstrate its high efficacy in clearing AK lesions with a favorable safety profile, leading to regulatory approval. The ease of use and short therapy duration (5 days) ensure patient compliance and satisfaction with the treatment. Conclusion: Further longitudinal studies are necessary to confirm the long-term benefits and positioning of tirbanibulin in AK therapy. Raising public awareness about AK and the importance of early treatment with effective options like tirbanibulin is crucial for improving public health outcomes.

Optimized compact fortified weight-prioritized convolutional network for swift skin lesion identification using dermoscopic images

Skin cancer is a leading cause of cancer-related mortality, posing a significant global health challenge. Early detection and treatment are crucial for survival rates. While dermoscopy is a valuable non-invasive imaging tool for diagnosing skin lesions, its reliance on the expertise of dermatologists introduces variability, affecting diagnostic reliability. Existing deep learning models for skin lesion analysis often prioritize accuracy over computational efficiency, limiting their practical application in clinical settings where both rapidity and precision are crucial. To address these limitations, this study proposes a novel model called the Compact Fortified Weight-Prioritized Convolutional Network (CWCN), optimized using the Harbor Seal Whiskers Optimization (HOA) algorithm (CWCN-HOA-SLD-DI). The CWCN is designed to offer a balance between high performance and computational efficiency. Initially, dermoscopic images from the ISIC Archive dataset are collected and subjected to a series of preprocessing steps, including image augmentation to enhance robustness, normalization using log-sinh with Adaptive Box-Cox transformation, and noise removal employing Guided Box Filtering (GBF) and Guided Image Filtering (GIF). The CWCN-HOA framework is then utilized to classify skin lesions into categories such as Malignant, Melanocytic Nevus, Basal Cell Carcinoma, Actinic Keratosis, Benign Keratosis, Dermatofibroma, and Vascular Lesion. The proposed CWCN-HOA-SLD-DI model is implemented in Python, and its performance is evaluated against current methods. The results indicate that the CWCN-HOA approach achieves significant improvements in both classification accuracy as 99.98% and computational efficiency as 92ms. By offering a combination of high performance and computational efficiency, the CWCN-HOA model represents a promising solution for accurate and efficient skin cancer detection. Its potential to improve the diagnostic capabilities of dermatologists and enhance patient outcomes underscores its significance in addressing this critical global health issue.

A Randomized Comparative study of efficacy and safety between %20 and %30 Hydrogen peroxide in the Treatment of Actinic keratosis

Background and objectives: Actinic keratosis is a premalignant skin lesion that presents clinically as a sand-like macule or papule on an erythematous base with a superficial scale due to atypical proliferation of keratinocytes and may progress to squamous cell carcinoma. The aim of this study was to compare the efficacy of hydrogen peroxide in treatment of actinic keratosis between two different concentrations (%20 and %30). Methods: This is a randomized open label therapeutic trial of twenty patients with actinic keratosis has been enrolled, it was conducted from April 2022 to August 2022 at Sulaimaniah dermatology teaching center. Patients were divided to two treatment groups. Hydrogen peroxide %20 applied to the actinic lesions of group A, while group B applied 30% Hydrogen peroxide to the lesions. The solution was applied to the lesions in a circular motion for 20 seconds, for four rounds per session Patients were seen after a first session in two weeks. Maximum four sessions spaced out by 15 days are given until clearance. Result: we conducted a randomized open label therapeutic trial. It was conducted from April 2022 to August 2022 at Sulaimaniah dermatology teaching center. Regarding response in Group A out of twenty actinic lesions, marked and moderate improvement was recorded in %40, %30 of the lesions respectively while the remaining lesions %30 of them showed slight improvement and no clinically clearance has been recorded. In comparsison, Group B out of twenty lesions %60 of them clinically cleared and slight improvement was recorded only in %20 of lesions. There were statistically significant differences between (20% &amp; 30% Hydrogen peroxide ) in response (p-value=0.000). Regarding side effects; majority of patients (85%) in both groups had recorded burning sensation, irritation and transient erythema, while no scarring, pigmentation, atrophy has been recorded. There were no statically significant differences between two groups. Conclusion: Hydrogen peroxide can be used as safe, alternative method to other modalities in treatment of actinic keratosis lesions, results would be better if higher concentration %30 used

Photographic scale for the characterization of actinic keratosis through reflectance confocal microscopy: a quantitative approach to cellular transformation.

Actinic keratosis (AK) is a highly prevalent pre-cancerous skin lesion that often leads to cutaneous squamous cell carcinoma. There are different stages of evolution of the disease and several features that characterize keratosis. This study aimed to develop a qualitative and quantitative visual diagnostic tool to facilitate the identification of the characteristics and severity of the main cellular attributes of AK and to show its applicability in evaluating the evolution or treatment through image analysis. Literature research on the main scientific databases and in the institute's database was carried out to gather all the different levels of cellular transformation. To validate the scale, a preliminary characterization study was carried out with 21 subjects who had clinically diagnosed AK lesions to classify the attributes in each skin layer and test the accuracy of the diagnosis of the scale. Afterward, and to show the possibility of a follow-up with a topical treatment, the subjects were divided into two treatment groups, receiving either a cream formulation containing retinoic acid, or a placebo formula. The evaluation was carried out through confocal reflectance microscopy and a digital camera with dermoscopic quality before and after 90 days of treatment. A table detailing the 18 attributes of AK, and a photographic scale containing RCM images graded by scores established for each characteristic and the frequency of spreading were developed. The results of the validation presented good repeatability, correlation with clinical evaluation, and capacity for differentiating treatments demonstrated by the significant improvement after topical treatment by the reduction of the score for 10 out of the 18 attributes. The preliminary study, evaluated by the detailed transformation scale highlights important differences in the subclinical approach that allows a deeper evaluation of the aspects of the lesion's re-incidence even after fully treated skin sites. This study brings an innovative method based on RCM, to assist in the quantification of cell transformation level, provide early diagnosis, and deliver a powerful treatment evaluation tool to provide smoother treatment, as well as prevent re-incidence in the cases.

Epidemiology and Risk Factors of Actinic Keratosis. What is New for The Management for Sun-Damaged Skin.

Actinic keratosis (AK) is considered a chronic skin disease mostly caused by long-term exposure to UV radiation and other risk factors such as immunosuppression, leading to an individual susceptibility for skin cancer manifestation. The treatment of AK is laborious and costly, and the incidence of skin cancer is forecasted to double until the year 2030 in an aging society.Risk factors in AK for malignant transformation in cutaneous squamous cell carcinoma (cSCC) are not fully understood, but studies suggest that histological features, such as atypia in the basal epidermal third and basal proliferation (PRO score) in AK play a pivotal role for development of malignancy. As the clinical appearance of AK does not correlate with the risk for malignancy, guidelines suggest treating every single AK lesion upon diagnosis. Skin imaging techniques, such as line-field confocal optical coherence tomography (LC-OCT) can help to provide an individual holistic follow-up for AK lesions by non-invasive visualization of atypia and basal proliferation. A follow-up for patients with AK may be critical for treatment success in terms of strengthening therapy adherence. When AK presents therapy refractory, cSCC manifests in nearly 30% of the cases after several years. Patients with AK suffering from field cancerization and immunosuppression are susceptible for a severe course of disease including metastasis and high mortality rates. Those vulnerable subgroups benefit from close skin cancer screening, early adequate treatment and chemoprevention, such as niacinamide or acitretin. Skin cancer prevention is substantial. Primary prevention should include chemical and physical UV-light protection and avoidance of indoor tanning. Secondary prevention is essential in high-risk populations, such as fair skin type elderly men and STORs. Tertiary prevention should comprise adequate treatment strategies to prevent therapy resistance, reoccurrence and cSCC, especially when field cancerization and immunosuppression are present.

Efficacy of Photodynamic Therapy in the Treatment of Actinic Keratosis: A Network Meta-Analysis.

Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) and uses different light sources as well as photosensitizers. In addition, PDT is often combined with other physical therapies or drugs. This study was aimed to compare the efficacy of different PDTs against AK lesions based on Complete Response (CR) by conducting a network meta-analysis (NMA). Randomized controlled trials (RCTs) using PDT for AK were screened and a Bayesian model was developed to perform an NMA of CR at 3 months after the first treatment. Twenty-six trials involving 2285 patients and 14 treatments were included. The treatments were broadly divided into mono-PDT and combination therapy. The photodynamic monotherapies included methyl 5-aminolevulinic acid (MAL)-daylight (DL)-PDT, MAL-light-emitting diode (LED)-PDT, 5-aminolevulinic acid (ALA)-LED-PDT, etc. Combination therapies included ablative fractional laser (AFL)-assisted MAL-LED-PDT, calcipotriol (CAL)-assisted MAL-LED-PDT, and 5-fluorouracil (5-Fu)-assisted MAL-DL-PDT. The results of the NMA showed that there is a high probability that AFL-MAL-LED-PDT is the most effective treatment option, followed by CAL-MAL-LED-PDT and ALA-LED-PDT. The subgroup analysis showed that MAL-based PDT had better efficacy when using LED versus other light sources, while LED-based PDT was likely to have better efficacy when using ALA versus other photosensitizers. The results of this NMA suggest that AFL-MAL-LED-PDT may be the superior choice for achieving complete clearance of AK lesions. PDT using LED as the light source and ALA as the photosensitizer may be more effective for the treatment of AK. However, more RCTs are needed to verify the results of this analysis.

Dynamic optical coherence tomography unveils subclinical, vascular differences across actinic keratosis grades I-III.

Actinic keratosis (AK) classification relies on clinical characteristics limited to the skin's surface. Incorporating sub-surface evaluation may improve the link between clinical classification and the underlying pathology. We aimed to apply dynamic optical coherence tomography (D-OCT) to characterize microvessels in AK I-III and photodamaged (PD) skin, thereby exploring its utility in enhancing clinical and dermatoscopic AK evaluation. This explorative study assessed AK I-III and PD on face or scalp. AK were graded according to the Olsen scheme before assessment with dermatoscopy and D-OCT. On D-OCT, vessel shapes, -pattern and -direction were qualitatively evaluated at predefined depths, while density and diameter were quantified. D-OCT's ability to differentiate between AK grades was compared with dermatoscopy. Forty-seven patients with AK I-III (n = 207) and PD (n = 87) were included. Qualitative D-OCT evaluation revealed vascular differences between AK grades and PD, particularly at a depth of 300 μm. The arrangement of vessel shapes around follicles differentiated AK II from PD (OR = 4.75, p < 0.001). Vessel patterns varied among AK grades and PD, showing structured patterns in AK I and PD, non-specific in AK II (OR = 2.16,p = 0.03) and mottled in AK III (OR = 29.94, p < 0.001). Vessel direction changed in AK II-III, with central vessel accentuation and radiating vessels appearing most frequently in AK III. Quantified vessel density was higher in AK I-II than PD (p ≤ 0.025), whereas diameter remained constant. D-OCT combined with dermatoscopy enabled precise differentiation of AK III versus AK I (AUC = 0.908) and II (AUC = 0.833). The qualitative and quantitative evaluation of vessels on D-OCT consistently showed increased vascularization and vessel disorganization in AK lesions of higher grades.

Comparison of therapeutic agents' short-term effects on facial and scalp actinic keratosis: A network meta-analysis.

Care for actinic keratosis (AK) can be improved with more knowledge on the relative of effect of indicated therapies. Using network meta-analyses, we quantitatively determined the comparative "short-term" effects of interventions in adults with facial and scalp AK. On February 28, 2023, evidence from the peer-reviewed literature was systematically obtained from OVID, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. We analyzed data from studies published in English, of a trial design, and investigating the effect of an actinic keratosis monotherapy. Patient complete clearance, patient partial clearance or lesion-specific clearance across adults were analyzed at 8-12 weeks after therapy. Patient complete clearance pertained to proportion of participants who experienced complete clearance of actinic keratosis lesions; patient partial clearance corresponded to percentage of subjects who achieved at least 75% clearance of actinic keratosis lesions; lesion-specific clearance represented the percentage of all lesions that were cleared. In the main (i.e., base) analyses, nodes were analyzed only at the level of the agent. Data from a total of 84 studies were used-across which 22 active agents were identified. Estimates of interventions' surface under the cumulative ranking curve rankings and (pairwise) relative effects were estimated. Across the three outcomes, fluorouracil 5% was ranked the most effective. Our work is the first to provide information on covariate-adjusted relative effects of actinic keratosis therapies- including the more recently reported treatments-for the face and scalp; this knowledge may help physicians and patients make more informed decisions.

Effective treatment of actinic keratosis on the hands with red light photodynamic therapy using BF-200 ALA

BackgroundAcral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands. MethodsWe analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10 % 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction. Results24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9 % (lesion-based) and 76.2 % (per participant's side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0 %. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0 %) rated their satisfaction with BF-200 ALA as very good or good. ConclusionThis subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands.

The "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) Project: An Expert Panel Opinion.

Actinic keratosis (AK) is an intraepithelial condition characterized by the development of scaly, erythematous lesions after repeated exposure to ultraviolet radiation. Significant immunosuppression is a risk factor for the development of AK and subsequent lesion progression to squamous cell carcinoma. Immunocompromised patients (ICPs), particularly organ transplant recipients, often have more advanced or complex AK presentations and an increased risk of skin carcinomas versus non-ICPs with AK, making lesions more difficult to treat and resulting in worse treatment outcomes. The recent "Personalising Actinic Keratosis Treatment" (PAKT) consensus reported that delivering patient-centric care may play a role in supporting better clinical outcomes and patient satisfaction with treatments for chronic dermatologic conditions such as AK, which require repeated cycles of treatment. Additionally, currently published guidance and recommendations were considered by the PAKT panel to be overly broad for managing ICPs with their unique and complex needs. Therefore, the "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) panel was established to build upon general recommendations from the PAKT consensus. The panel identified current gaps in guidance for AK care in ICPs, offered practical care approaches based on typical ICP scenarios, and highlighted the need to adapt AK management to optimize care and improve treatment outcomes in ICPs. In particular, dermatologists should establish collaborative and transparent relationships with patients' multidisciplinary teams to enhance overall care for patients' comorbidities: given their increased risk of progression to malignancy, earlier assessments/interventions and frequent follow-ups are vital.The panel also developed a novel "triage" tool outlining effective treatment follow-up and disease surveillance plans tailored to patients' risk profiles, guided by current clinical presentation and relevant medical history. Additionally, we present the panel's expert opinion on three fictional ICP scenarios to explain their decision-making process for assessing and managing typical ICPs that they may encounter in clinical practice.

Actinic keratosis: Current challenges and unanswered questions.

Actinic keratoses (AK) are common skin lesions associated with chronic exposure to sun. They are believed to be precursors of malignancy as they potentially may progress to invasive squamous cell carcinomas. The goal of current therapies is to reduce the number of AK and to prevent future cancer development. This review aims at providing an overview of the hallmarks of AK and skin field cancerization. We discuss epidemiology trends, risk factors and the state of the art and evidence of the current treatments. We review key figures of AK prevalence from different countries with regard to skin cancer risk and the associated economic burden of AK. We discuss the mutational status in AK lesions and the difficulties encountered by clinicians in evaluating AK visible and invisible lesions, referring to the concept of field cancerization. Based on a systematic literature review, we further evaluate the available treatment options. The presence of subclinical skin alterations in the periphery of visible AK lesions has gained a particular attention as those non-visible lesions are known to contain the same genetic changes as those found in the AK lesions themselves, prompting the concept of 'field cancerization'. Therefore, AK treatment guidelines now recognize the importance of treating the field in patients with AK. A recent systematic literature review and network meta-analysis showed that 5-FU interventions were associated with the best efficacy and a satisfactory acceptability profile compared with other field-directed therapies used in the treatment of AK. Although AK are considered quite common, they lack an accurate descriptive definition and conclusive epidemiologic data. Limited public awareness is a barrier to early and effective treatment, including prevention strategies. While different treatment options are available, there is still a limited understanding of long-term outcomes of treatment as measured by recurrence of cancer prevention.

Patient- and Clinician-Reported Outcomes for Tirbanibulin in Actinic Keratosis in Clinical Practice Across the United States (PROAK).

The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.&nbsp; Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P&lt;0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

Combination of 5-fluorouracil with photodynamic therapy enhances immune responses in a murine model of actinic keratosis

SignificancePhotodynamic therapy (PDT) to treat actinic keratoses (AK) involves application of a photosensitizer followed by exposure to light, resulting in effective lesion clearance by inducing cell death and long-term immune responses. Here, we show that pretreatment of AK lesions with 5-fluorouracil (5FU) causes significant enhancement of PDT-related immune effects. ApproachSKH-1 mice with AK (generated by repeated UVB exposure) were treated topically with 5FU for three days prior to application of topical ALA followed by blue light exposure. AK lesions were harvested for time-course analyses of intra-tumoral immune responses after PDT with or without 5FU. ResultsImmunofluorescence data showed that 5FU pretreatment increased recruitment of innate immune cells, infiltration of activated T cells and of cytotoxic T cells and reduced the presence of cells expressing the immune checkpoint marker PD1. ConclusionsOur results suggest that a combination of 5FU and PDT may synergize to provide better management of AK in the dermatology clinic.

Characterization of the skin microbiome in normal and cutaneous squamous cell carcinoma affected cats and dogs.

The progression of precancerous actinic keratosis lesions (AK) to cutaneous squamous cell carcinoma (SCC) is poorly understood in humans and companion animals, despite causing a significant burden of disease. Recent studies have revealed that the microbiota may play a significant role in disease progression. Staphylococcus aureus has been found in high abundance on AK and SCC lesions, where it secretes DNA-damaging toxins, which could potentiate tumorigenesis. Currently, a suitable animal model to investigate this relationship is lacking. Thus, we examined the microbiome of cutaneous SCC in pets, revealing similarities to humans, with increased staphylococci and reduced commensals on SCC lesions and peri-lesional skin compared to normal skin. Two genera that were in abundance in SCC samples have also been found in human oral SCC lesions. These findings suggest the potential suitability of pets as a model for studying microbiome-related skin cancer progression.

Home- vs clinic-based daylight photodynamic therapy with 5-aminolevulinic acid nanoemulsion (BF-200 ALA) for actinic keratosis: A randomized, single-blind, prospective study

BackgroundDaylight photodynamic therapy (DL-PDT) has become one of the most effective treatments for the resolution of actinic keratosis (AK) of Olsen grade 1 and 2. Generally, PDT it is carried out in a clinic setting, which involves the patient's and their caregivers commuting to the hospital as well as a significant use of resources to carry it out within the clinic setting. ObjectivesTo determine the efficacy and safety of a home-based treatment of AK with DL-PDT with the BF-200 ALA gel compared to a clinic-based setting. MethodsThe study was performed as a randomized, single-center, non-inferiority clinical trial with two parallel groups. 9 patients received one clinic-based DL-PDT (group 1) and 11 patients received one session of home-based DL-PDT (group 2). The primary endpoints were the mean AK clearance per patient and the total AK lesion clearance rate 12 weeks after treatment. The secondary endpoints were the number of remaining AKs and new AKs appearing in the treatment field 12 weeks after one PDT session. The pain during and 24 h after PDT as well as the local skin reactions were also assessed. ResultsThe overall reduction of AK lesions per patient was similar in both groups with one PDT session. An overall AK clearance per patient of 10 ± 4.33 for group 1 versus 9.73 ± 2.9 for group 2 without statistically significant differences (p = 0.868). Regarding the clearance rate, although it was slightly higher in group 2 (71.58 ± 22.51 vs 82.1 ± 11.13), the analysis did not show statistically significant differences. The mild pain recorded during the treatment course and the mild local skin reactions were similar in both groups. Patient satisfaction was high for both groups without statistically significant differences. ConclusionSelf-performed home-based DL-PDT with BF-200 ALA gel is as effective as the one performed in a clinic-based setting, with a comparable safety profile, high levels of patient satisfaction and with advantages for the patients and their caregivers that can enhance patient´s adherence to the treatment

Combination of vitamin D and photodynamic therapy enhances immune responses in murine models of squamous cell skin cancer

Improved treatment outcomes for non-melanoma skin cancers can be achieved if Vitamin D (Vit D) is used as a neoadjuvant prior to photodynamic therapy (PDT). However, the mechanisms for this effect are unclear. Vit D elevates protoporphyrin (PpIX) levels within tumor cells, but also exerts immune-modulatory effects. Here, two murine models, UVB-induced actinic keratoses (AK) and human squamous cell carcinoma (A431) xenografts, were used to analyze the time course of local and systemic immune responses after PDT ± Vit D. Fluorescence immunohistochemistry of tissues and flow analysis (FACS) of blood were employed. In tissue, damage-associated molecular patterns (DAMPs) were increased, and infiltration of neutrophils (Ly6G+), macrophages (F4/80+), and dendritic cells (CD11c+) were observed. In most cases, Vit D alone or PDT alone increased cell recruitment, but Vit D + PDT showed even greater recruitment effects. Similarly for T cells, increased infiltration of total (CD3+), cytotoxic (CD8+) and regulatory (FoxP3+) T-cells was observed after Vit D or PDT, but the increase was even greater with the combination. FACS analysis revealed a variety of interesting changes in circulating immune cell levels. In particular, neutrophils decreased in the blood after Vit D, consistent with migration of neutrophils into AK lesions. Levels of cells expressing the PD-1+ checkpoint receptor were reduced in AKs following Vit D, potentially counteracting PD-1+ elevations seen after PDT alone. In summary, Vit D and ALA-PDT, two treatments with individual immunogenic effects, may be advantageous in combination to improve treatment efficacy and management of AK in the dermatology clinic.

Expression Analysis of Retinal G Protein-coupled Receptor and its Correlation with Regulation of the Balance between Proliferation and Aberrant Differentiation in Cutaneous Squamous Cell Carcinoma.

Retinal G protein-coupled receptor (RGR), a photosensitive protein, functions as a retinal photoisomerase under light conditions in humans. Cutaneous squamous cell carcinoma (cSCC) is linked to chronic ultraviolet exposure, which suggests that the photoreceptor RGR may be associated with tumorigenesis and progression of squamous cell carcinoma (SCC). However, the expression and function of RGR remain uncharacterized in SCC. This study analysed RGR expression in normal skin and in lesions of actinic keratosis, Bowen's disease and invasive SCC of the skin with respect to SCC initiation and development. A total of 237 samples (normal skin (n = 28), actinic keratosis (n = 42), Bowen's (n = 35) and invasive SCC (n = 132) lesions) were examined using immunohistochemistry. Invasive SCC samples had higher expression of RGR protein than the other samples. A high immunohistochemical score for RGR was associated with increased tumour size, tumour depth, Clark level, factor classification, and degree of differentiation and a more aggressive histological subtype. In addition, RGR expression was inversely correlated with involucrin expression and positively correlated with proliferating cell nuclear antigen (PCNA) and Ki67 expression. Furthermore, RGR regulates SCC cell differentiation through the PI3K-Akt signalling pathway, as determined using molecular biology approaches in vitro, suggesting that high expression of RGR is associated with aberrant proliferation and differentiation in SCC.

Shedding new light on actinic keratoses and squamous cell carcinoma in situ.

Cutaneous squamous cell carcinoma can arise from various premalignant lesions such as actinic keratosis, Bowen disease, and premalignant genital squamous cell lesions. Identification and treatment can prevent malignant transformation and death. This article describes the causes, epidemiology, and characteristics of suspicious premalignant squamous cell lesions so that clinicians can identify these lesions and refer patients for specialist treatment as appropriate.

Assessment of reflectance confocal microscopy for monitoring treatment of actinic keratosis and field cancerization with daylight photodynamic therapy.

Actinic keratosis (AK) is the most common pre-malignant cutaneous lesion of the skin, often associated with field cancerization. Daylight photodynamic therapy (DL-PDT) is used as treatment, showing good histological results. Reflectance confocal microscopy (RCM) may be useful as a non-invasive, real-time approach to monitor treatment, however, there is a lack of data on the correlation between RCM and histopathological findings in AK patients treated with DL-PDT. To correlate histological and RCM findings and evaluate the efficacy of DL-PDT in patients with AK and field cancerization treated with DL-PDT. Patients with field cancerization and a minimum of six AK lesions on the face were included in the study. A single session combining methyl aminolevulinate followed by two-hour daylight exposure of the face was performed. RCM and biopsy were performed before and after three months of the intervention to compare efficacy between patients using the Wilcoxon test, and concordance of the findings based on the different methods was analysed using the Kappa test. Twenty-four patients completed the study. An improvement in photodamage and a decrease in the number of AK lesions (45.3% reduction) was observed. Regression in atypia and dysplasia was observed via histopathology and RCM, however, there was poor agreement between the methods. No changes were observed after treatment for inflammation, fibroplasia and acantholysis. Concordance between histological and RCM findings was poor, suggesting that RCM cannot replace the histopathological examination, however, it may be used as an adjuvant test for follow-up of patients. Despite this, DL-PDT proved to be an effective method for treating AK.