Search Results (37)

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Background/Objectives: Skin lesions, ranging from benign to malignant diseases, are a difficult dermatological condition due to their great diversity and variable severity. Their detection at an early stage and proper classification, particularly between benign Nevus (NV), precancerous Actinic Keratosis (AK), and Squamous Cell Carcinoma (SCC), are crucial for improving the effectiveness of treatment and patient prognosis. The goal of this study was to test deep learning (DL) models to determine the best architecture to use in classifying lesions and create a web-based platform for improved diagnostic and educational availability. Methods: Various DL models, like Xception, DenseNet169, ResNet152V2, InceptionV3, MobileNetV2, EfficientNetV2 Small, and NASNetMobile, were compared for classification accuracy. The top model was incorporated into a web application, allowing users to upload images for automatic classification, thereby offering confidence scores as a measure of the reliability of predictions. The tool also has enhanced visualization capabilities, which allow users to investigate feature maps derived from convolutional layers, enhancing interpretability. Web scraping and summarization techniques were also employed to offer concise, evidence-based dermatological information from established sources. Results: Of the models evaluated, DenseNet169 achieved the best classification accuracy of 85% and was, therefore, chosen as the base architecture for the web application. The application enhances diagnostic clarity by visualizing features and promotes access to trustworthy medical information on dermatological disorders. Conclusions: The developed web application serves as both a diagnostic support system for dermatologists and an educational system for the general public. By using DL-based classification, interpretability techniques, and automatic medical information extraction, it facilitates early intervention and increases awareness regarding skin health. Full article

Hydroxyurea (HU), a cornerstone treatment for myeloproliferative disorders, is associated with a wide range of cutaneous side effects, from xerosis and hyperpigmentation to more severe conditions like dermatomyositis-like eruptions (DM-LE) and nonmelanoma skin cancers (NMSC), particularly squamous cell carcinoma (SCC). In this review, we present a unique case of HU-induced DM-LE with histological evidence of keratinocyte dysplasia and p53 overexpression, followed by a systematic analysis of similar cases. Our findings reveal that the clinical presentation of DM-LE, while typically considered benign, shares clinical and histological features with hydroxyurea-associated squamous dysplasia (HUSD), a precancerous condition that may progress to SCC in chronically exposed patients. Key insights include the characteristic histopathological findings of DM-LE, the role of chronic HU therapy and UV-induced damage in promoting p53 overexpression, and the overlap between DM-LE and HUSD. Regular dermatologic monitoring, patient education on photoprotection, and the careful assessment of skin lesions in long-term HU users are essential for the early detection and prevention of malignancies. This review underscores the importance of distinguishing between DM-LE, HUSD, and SCC to optimize management and minimize risks associated with HU therapy. Full article

Background/Objectives: People living with HIV (PLWH) are more susceptible than immunocompetent people to non-melanoma skin cancers. These tumors can arise de novo or from precancerous lesions, such as actinic keratosis (AKs). The management of AKs in PLWH has not been widely discussed in the literature. More specifically, the efficacy of the treatment of AKs in PLWH with modern topical drugs, such as tirbanibulin, is limited. The present work aims to evaluate the response rate to the intervention with tirbanibulin 1% ointment for treating AKs in PLWH. Methods: We retrospectively collected the data of the PLWH who visited the Dermatology Department of the Policlinico Riuniti (Foggia, Italy) between September 2023 and September 2024. PLWH who received the diagnosis of AKs and underwent treatment with tirbanibulin 1% ointment were studied. To assess the severity of AKs, the number of AKs and the AKs’ area and severity index (AKASI) score were calculated at the time of diagnosis (T0) and after treatment (T1). Results: Ten PLWH were found to have AKs and received topical therapy with tirbanibulin 1% ointment. On average, at T0, the number of lesions was 8.2 and the AKASI score was 4.20; at T1, the number of AKs was 1.7 and the AKASI score was 1.5. Only two patients reported a mild inflammatory reaction to applying tirbanibulin 1% ointment. Conclusions: The rate of satisfactory responses was in line with a recent multicentric Italian study performed on immunocompetent patients. Our results confirm the efficacy and tolerability of tirbanibulin 1% ointment in treating AKs in PLWH in particular. Full article

Background and Objectives: Actinic keratosis (AK) is a precancerous cutaneous lesion driven by chronic ultraviolet (UV) exposure, often coexisting with features of photoaging, such as wrinkles and pigmentary irregularities. Recent evidence suggests that treatments for AK may also counteract photoaging through shared molecular pathways, including oxidative stress and inflammation. This narrative review explores the dual benefits of AK therapies, highlighting their potential anti-aging and skin-lightening effects, and implications for improving skin appearance alongside lesion clearance. Materials and Methods: The literature was analyzed to assess the efficacy, mechanisms, and cosmetic outcomes of commonly used AK treatments, including topical agents (5-fluorouracil (5-FU), imiquimod, diclofenac, and tirbanibulin), and photodynamic therapy (PDT). Studies highlighting their effects on photoaged skin, collagen remodeling, pigmentation, and patient satisfaction were reviewed. Results: PDT emerged as the most validated treatment, demonstrating improved collagen synthesis, skin texture, and pigmentation. 5-FU showed remodeling of the dermal matrix and increased procollagen levels, but local skin reactions represent a major limitation. Imiquimod enhanced dermal fibroplasia and reduced solar elastosis, while diclofenac provided mild photodamage improvements with minimal adverse effects. Tirbanibulin showed promising aesthetic outcomes, including skin lightening and a reduction in mottled pigmentation, with favorable tolerability. Conclusions: AK therapies offer a dual-purpose strategy, addressing both precancerous lesions and cosmetic concerns associated with photoaging. While PDT remains the gold standard, emerging agents like tirbanibulin ointment exhibit substantial potential. Future research should focus on optimizing treatment protocols and evaluating long-term cosmetic outcomes to enhance patient satisfaction and compliance. Full article

Porokeratoses represent a rare group of skin diseases characterized by abnormal keratinization. The condition may have a genetic background and can be triggered by environmental factors, including UV exposure and infections. Several clinical variants of porokeratosis can be distinguished, including Mibelli’s porokeratosis, disseminated superficial actinic porokeratosis, superficial disseminated porokeratosis, and porokeratosis palmaris plantaris et disseminata. Diagnosis is established based on clinical and histopathological examination, dermatoscopy, and reflectance confocal microscopy. Various treatment options are available, including topical combination therapy with cholesterol and statins, topical retinoids, cryotherapy, laser therapy, and surgical excision of lesions, but none are fully effective. The success of these treatments can vary significantly based on the specific type of porokeratosis and individual patient characteristics, with many outcomes falling short of expectations. Since the disease is considered a precancerous condition, patients with porokeratosis should remain under regular dermatological control. Full article

The primary aim of this study was to evaluate the activation of the PERP and Akt oncogenes in the induction of skin cancer in FVB/N mice by a stepwise chemical process. Forty four-week-old female FVB/N mice were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). In the study, the groups were subjected to a two-stage carcinogenesis procedure. This consisted of an initial application of 97.4 nmol DMBA to shaved skin on the back, followed by applications of 32.4 nmol TPA after thirteen weeks for group A and after twenty weeks for group B. The control group received no treatment. Skin conditions were monitored weekly for tumor development. At the end of the experiment, the animals were euthanized for further tissue sampling. Examination of the skin lesions in the experimental groups showed a correlation with tumor progression, ranging from dysplasia to carcinoma. Tumor samples were examined both histologically and immunohistochemically. Notably, and PERP expression was higher in precancerous than in malignant tumors. The differences in expression between precancerous and benign tumors provide further evidence of a role for PERP and Akt in the transition from benign to malignant states. Our findings underscore the critical roles of PERP and Akt in the pathogenesis of skin cancer and suggest their potential as biomarkers for early detection and targets for therapeutic intervention. Full article

Cutaneous squamous cell carcinoma (cSCC) is a common and increasingly prevalent form of skin cancer, posing significant health challenges. Understanding the molecular mechanisms involved in cSCC progression is crucial for developing effective treatments. The primary aim of this research was to evaluate the activation of NOTCH1 and FGFR2 oncogenes in inducing skin cancer in FVB/N mice through a stepwise chemical process. Forty female FVB/N mice, aged four weeks, were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). This study involved subjecting the groups to a two-stage carcinogenesis procedure. This included an initial application of 97.4 nmol DMBA on shaved skin on their backs, followed by applications of 32.4 nmol TPA after thirteen weeks for group A and after twenty weeks for group B. The control group did not receive any treatment. Their skin conditions were monitored weekly to detect tumor development. After the experiment, the animals were euthanized for further tissue sampling. The examination of skin lesions in the experimental groups showed a correlation with tumor progression, ranging from dysplasia to carcinoma. Tumor samples were assessed both histologically and immunohistochemically. Notably, FGFR2 expression was higher in benign, precancerous, and malignant tumors compared to normal tissue. NOTCH1 expression was only elevated in benign tumors compared to normal tissue. This study demonstrates a clear correlation of FGFR2 expression and the progression of cutaneous neoplasms, while NOTCH 1 expression is inversely correlated in FVB/N mice. This suggests an early involvement of these oncogenes in the development of skin tumors. Full article

Cutaneous field cancerization (CFC) refers to a skin region containing mutated cells’ clones, predominantly arising from chronic exposure to ultraviolet radiation (UVR), which exhibits an elevated risk of developing precancerous and neoplastic lesions. Despite extensive research, many molecular aspects of CFC still need to be better understood. In this study, we conducted ex vivo assessment of cell differentiation, oxidative stress, inflammation, and DNA damage in CFC samples. We collected perilesional skin from 41 patients with skin cancer and non-photoexposed skin from 25 healthy control individuals. These biopsies were either paraffin-embedded for indirect immunofluorescence and immunohistochemistry stain or processed for proteins and mRNA extraction from the epidermidis. Our findings indicate a downregulation of p53 expression and an upregulation of Ki67 and p16 in CFC tissues. Additionally, there were alterations in keratinocyte differentiation markers, disrupted cell differentiation, increased expression of iNOS and proinflammatory cytokines IL-6 and IL-8, along with evidence of oxidative DNA damage. Collectively, our results suggest that despite its outwardly normal appearance, CFC tissue shows early signs of DNA damage, an active inflammatory state, oxidative stress, abnormal cell proliferation and differentiation. Full article

This comprehensive review delves into various immunotherapeutic approaches for the management of actinic keratoses (AKs), precancerous skin lesions associated with UV exposure. Although there are treatments whose main mechanism of action is immune modulation, such as imiquimod or diclofenac, other treatments, apart from their main effect on dysplastic cells, exert some immunological action, which in the end contributes to their efficacy. While treatments like 5-fluorouracil, imiquimod, photodynamic therapy, and nicotinamide are promising in the management of AKs, especially in immunocompetent individuals, their efficacy is somewhat reduced in solid organ transplant recipients due to immunosuppression. The analysis extends to optimal combination, focusing on cryoimmunotherapy as the most relevant. New immunotherapies include resimiquimod, ingenol disoxate, N-phosphonacetyl-L-aspartate (PALA), or anti-PD1 that have shown promising results, although more studies are needed in order to standardize their use. Full article

ALA PDT, first approved as a topical therapy to treat precancerous skin lesions in 1999, targets the heme pathway selectively in cancers. When provided with excess ALA, the fluorescent photosensitizer PpIX accumulates primarily in cancer tissue, and ALA PDD is used to identify bladder and brain cancers as a visual aid for surgical resection. ALA PDT has shown promising anecdotal clinical results in recurrent glioblastoma multiforme. ALA SDT represents a noninvasive way to activate ALA PDT and has the potential to achieve clinical success in the treatment of both intracranial and extracranial cancers. This review describes the creation and evolution of ALA PDT, from the treatment of skin cancers to PDD and PDT of malignant brain tumors and, most recently, into a noninvasive form of PDT, ALA SDT. Current clinical trials of ALA SDT for recurrent glioblastoma and high-grade gliomas in adults, and the first pediatric ALA SDT clinical trial for a lethal brainstem cancer, diffuse intrinsic pontine glioma (DIPG), are also described. Full article

Background: Teledermatology is employed in the diagnosis and follow-up of skin cancer and its use was intensified during and after the COVID-19 pandemic. At the same time, demographic changes result in an overall increase in non-melanoma skin cancer and skin precancerous lesions. The aim of this study was to elucidate the role of teledermatology in comparison to conventional face-to-face dermatology for such lesions and determine the advantages and limitations of this workflow for patients and physicians. Methods: Research was performed using relevant keywords in MEDLINE and CENTRAL. Relevant articles were chosen following a predetermined standardized extraction form. Results: Diagnostic accuracy and interrater/intrarater agreement can be considered comparable—although lower—than in-person consultation. Improvement of particular features such as image quality, medical history availability, and teledermoscopy can further increase accuracy. Further aspects of limitations and advantages (mean time-to-assessment, time-to-treatment, cost-effectiveness) are discussed. Conclusions: Teledermatology has comparable diagnostic accuracy with face-to-face dermatology and can be utilized both for the effective triage of non-melanocytic epithelial tumors and precancerous lesions, as well as the follow-up. Easy access to dermatologic consultation with shorter mean times to diagnostic biopsy and/or treatment coupled with cost-effectiveness could compensate for the lower sensitivity of teledermatology and offer easier access to medical care to the affected populations. Full article

Non-melanocytic skin cancers represent an important public health problem due to the increasing incidence and the important local destructive potential. Thus, the early diagnosis and treatment of precancerous lesions (actinic keratoses) is a priority for the dermatologist. In recent years, non-invasive skin imaging methods have seen an important development, moving from simple observational methods used in clinical research, to true diagnostic and treatment methods that make the dermatologist’s life easier. Given the frequency of these precancerous lesions, their location on photo-exposed areas, as well as the long treatment periods, with variable, imprecise end-points, the need to use non-invasive imaging devices is increasingly evident to complete the clinical observations in the diagnosis and treatment of these lesions, with the aim of increasing accuracy and decreasing the adverse effects due to long treatment duration. This is the first review that brings together all skin imaging methods (dermoscopy, reflectance confocal microscopy, ultrasonography, dermoscopy-guided high frequency ultrasonography, and optical coherence tomography) used in the evaluation of actinic keratoses and their response to different treatment regimens. Full article

This original article presents the findings of a comprehensive case series, shedding light on the efficacy of diverse treatment modalities for managing precancerous and cancerous skin lesions and their remarkable rejuvenation effects on the skin. A particular focus is placed on the promising outcomes achieved through the application of a combination treatment involving 5-Fluorouracil (5-FU) and salicylic acid, which demonstrates enduring and noteworthy results. Furthermore, alternative therapeutic approaches, including 5-FU monotherapy, Methyl aminolevulinate–photodynamic therapy (MAL-PDT), and the combination of Imiquimod therapy with MAL-PDT, exhibit substantial potential for patients seeking non-surgical solutions. These treatments manifest as valuable tools in improving skin texture and mitigating the effects of photodamage. Nevertheless, the intricate interplay between the chosen treatment, the extent of photodamage, and individual patient characteristics, with a particular emphasis on age, necessitates long-term follow-up to gauge treatment outcomes and the likelihood of lesion recurrence. Notably, these treatments are associated with a significant degree of inflammation, igniting curiosity regarding enhanced skin cellular turnover and the potential for a more youthful skin appearance. Our findings accentuate the promise of topical fluorouracil (5-FU) and photodynamic therapy (PDT) in combating photoaging among patients with actinic keratoses. However, a need for further in-depth research is evident to unravel the nuanced relationships between these treatments, the severity of photodamage, and the influence of patient-specific factors. Such comprehensive investigations are instrumental in optimizing patient care and outcomes, offering a holistic approach to managing photodamage within the context of actinic keratoses. This work, when combined with existing literature, provides valuable insights and serves as a catalyst for future research to fully unlock the potential of these treatments, ultimately enhancing the quality of patient care. Full article

Background: Actinic keratosis is a common precancerous skin lesion that can progress into invasive squamous cell carcinomas. Many topical treatments for actinic keratoses often have poor tolerability and prolonged duration. Tirbanibulin is a novel synthetic drug with potent antitumor and antiproliferative activities. Methods: We conducted a single-center, prospective and observational study using tirbanibulin ointment on a 25 cm² area for 5 consecutive days on 30 participants with AKs on the face or scalp. They were followed for at least 57 days to assess the safety profile and efficacy of the drug as well as treatment satisfaction. We evaluated six signs of local skin reaction (LSR): erythema, scaling, crusting, swelling, blisters/pustules, and erosions/ulcerations, grading the severity as mild, moderate, or severe. The effectiveness was evaluated both clinically and dermoscopically. The treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4). Results: On day 57, 70% of the patients showed a complete clinical and dermoscopic response. The highest scores obtained from the TSQM 1.4 were more evident in the convenience and side effects domains. Most LSRs, including erythema (83.3%), scaling (30%), and swelling (3.3%), occurred on day 8 but resolved spontaneously. Conclusion: Tirbanibulin is a viable therapeutic option with a short regimen treatment and good tolerability, which favors therapy adherence. Full article