ABSTRACT
BACKGROUND: Australian general practice patients commonly have significant solar damage. This can lead to the manifestation of actinic keratoses (AKs) as discreet lesions or as field disease, with these lesions potentially giving rise to keratinocyte cancers (KCs). Therefore, a pragmatic approach is needed to assess and manage these higher-risk patients. OBJECTIVE: This article discusses an approach to managing patients with significant solar damage from a primary care perspective, focusing on the assessment and treatment of AKs as individual lesions and within a field. DISCUSSION: Significant solar damage is typified by the presence of AKs, commonly seen as field disease. Several field treatment modalities are available for patients. Treatment options need to be tailored to the individual patient and site of disease to maximise adherence and efficacy.
Subject(s)
Keratosis, Actinic , Primary Health Care , Humans , Keratosis, Actinic/therapy , Australia , Sunlight/adverse effects , Skin Neoplasms/therapyABSTRACT
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.
Subject(s)
Keratosis, Actinic , Tomography, Optical Coherence , Tomography, Optical Coherence/methods , Humans , Keratosis, Actinic/diagnostic imaging , Keratosis, Actinic/pathology , Aged , Female , Male , Middle Aged , Dermoscopy/methods , Microvessels/diagnostic imaging , Microvessels/pathology , Aged, 80 and over , Scalp/diagnostic imaging , Scalp/blood supply , Scalp/pathology , Skin/blood supply , Skin/diagnostic imaging , Skin/pathology , Severity of Illness IndexABSTRACT
Keratinocyte-derived skin cancers comprise basal cell carcinoma, squamous cell carcinoma, its precursor actinic keratosis, and Bowen's disease. Historically, this group of neoplasms has been subsumed under the term non-melanoma skin cancer. However, the term non-melanoma skin cancer can be misleading and lacks precision. Therefore, more precise and reasonable terminology, valuing the relevance of keratinocyte-derived cancer, appears pertinent to meet its clinical and scientific significance. A group of experienced dermato-oncologists initiated a consensus approach to promote the use of the term "keratinocyte cancer" instead of "non-melanoma skin cancer" when referring to carcinomas and their precursors that are derived from keratinocytes. The vote among members of the consensus group indicated unanimous agreement on the consistent use of the term "keratinocyte cancer" instead of "non-melanoma skin cancer". International delegates also voted in favour of the revised terminology. The more precise and, by means of etiopathogenesis, correct term "keratinocyte cancer" should be consistently used for malignancies originated from keratinocytes. This is expected to have a positive impact on patient-physician communication and gives better justice to this important group of keratinocyte-derived cancers.
Subject(s)
Carcinoma, Basal Cell , Carcinoma, Squamous Cell , Consensus , Keratinocytes , Keratosis, Actinic , Skin Neoplasms , Terminology as Topic , Humans , Skin Neoplasms/pathology , Keratinocytes/pathology , Carcinoma, Basal Cell/pathology , Carcinoma, Squamous Cell/pathology , Keratosis, Actinic/pathology , Keratosis, Actinic/diagnosis , Bowen's Disease/pathology , EuropeABSTRACT
Actinic keratosis (AK) is a common precancerous skin condition predominantly affecting older males with fair skin and significant UV exposure. The clinical significance of AK is related to its potential for malignant transformation and progression to squamous cell carcinoma (SCC). Accurate diagnosis of AK is essential for adequate treatment, evaluation of therapeutic efficacy, and mitigating the risk of developing SCC. However, clinician variability due to the subjective nature of current diagnostic tools presents significant challenges to achieving consistent and reliable AK diagnoses. Thus, there is no universally accepted standard for measuring AK.This review evaluates current methods for evaluating and diagnosing AK, focusing on clinician variability through inter- and intraobserver agreement. Eight peer-reviewed studies investigating the reliability of various approaches for AK evaluation show substantial variability in interobserver or intraobserver agreement, with most methods demonstrating only slight to moderate reliability. Some suggest that consensus discussions and simplified rating scales can modestly improve diagnostic reliability. However, remaining variability and the lack of a universally accepted standard for measuring AK underscore the need for more robust and standardized diagnostic and evaluation methods.The review emphasizes the need for improved diagnostic tools and standardized methods to enhance the accuracy and reliability of AK assessments. It also proposes applying a novel examination approach using 1,3-dihydroxyacetone (DHA) staining which may improve the visualization and identification of AK lesions. Advancements in these areas have significant potential, promising better clinical practices and patient outcomes in AK management.
Subject(s)
Keratosis, Actinic , Skin Neoplasms , Humans , Keratosis, Actinic/diagnosis , Keratosis, Actinic/pathology , Keratosis, Actinic/therapy , Reproducibility of Results , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Observer Variation , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Skin/pathology , Precancerous Conditions/diagnosis , Precancerous Conditions/pathologyABSTRACT
BACKGROUND: Numerous meta-analyses and clinical studies have shown that subtypes of immune cells are associated with the development of skin cancer, but it is not clear whether this association is causal or biased. Mendelian randomization (MR) analysis reduces the effect of confounding factors and improves the accuracy of the results when compared to traditional studies. Thus, in order to examine the causal relationship between various immune cell and skin cancer, this study employs two-sample MR. METHODS: This study assesses the causal association between 731 immune cell characteristics and skin cancer using a two-sample Mendel randomization (MR) methodology. Multiple MR methods were used to bias and to derive reliable estimates of causality between instrumental variables and outcomes. Comprehensive sensitivity analyses were used to validate the stability, heterogeneity and horizontal multiplicity of the results. RESULTS: We discovered that potential causal relationships between different types of immune cells and skin cancer disease. Specifically, one type of immune cell as potentially causal to malignant melanoma of skin (MM), eight different types of immune cells as potentially causal to basal cell carcinoma (BCC), four different types of immune cells as potentially causal to actinic keratosis (AK), and no different types of immune cells were found to have a potential causal association with squamous cell carcinoma(SCC), with stability in all of the results. CONCLUSION: This study demonstrates the close connection between immune cells and skin cancer disease by genetic means, which enriches the current knowledge about the role of immune cells in skin cancer and also contributes to the design of therapeutic strategies from an immunological perspective.
Subject(s)
Melanoma , Mendelian Randomization Analysis , Skin Neoplasms , Humans , Skin Neoplasms/genetics , Skin Neoplasms/immunology , Melanoma/genetics , Melanoma/immunology , Carcinoma, Basal Cell/genetics , Carcinoma, Basal Cell/immunology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Keratosis, Actinic/genetics , Keratosis, Actinic/immunology , Polymorphism, Single NucleotideABSTRACT
Nonmelanocytic skin cancers (NMSCs) are currently the most common group of human cancers and include all tumors that are not melanomas. Increased exposure to sunlight over the past few years, the lack of regular and proper use of sunscreen, the aging of the population, and better screening techniques are the reasons for the escalation in their diagnosis. Squamous cell carcinoma (SCC) comprises nearly 37% of the tumors in this group and can originate from actinic keratosis (AK), which usually presents as pink, often scaly plaques, usually located on the face or scalp. Advances in dermatoscopy, as well as the development of other non-invasive skin imaging modalities such as high-frequency ultrasound (HFUS), reflectance confocal microscopy (RCM), and optical coherence tomography (OCT), have allowed for greatly increased sensitivity in diagnosing these lesions and monitoring their treatment. Since AK therapy is usually local, and SCCs must be removed surgically, non-invasive imaging methods enable to correctly qualify difficult lesions. This is especially important given that they are very often located on the face, and achieving an appropriate cosmetic result after treatments in this area is very important for the patients. In this review, the authors describe the use of non-invasive skin imaging methods in the diagnosis of actinic keratosis.
Subject(s)
Keratosis, Actinic , Skin Neoplasms , Tomography, Optical Coherence , Keratosis, Actinic/diagnostic imaging , Humans , Tomography, Optical Coherence/methods , Skin Neoplasms/diagnostic imaging , Microscopy, Confocal/methods , Carcinoma, Squamous Cell/diagnostic imaging , Dermoscopy/methods , Ultrasonography/methodsABSTRACT
Despite epidermal turnover, the skin is host to a complex array of microbes, including viruses, such as HPV, which must infect and manipulate skin keratinocyte stem cells (KSCs) to survive. This crosstalk between the virome and KSC populations remains largely unknown. Here, we investigated the effect of HPV8 on KSCs using various mouse models. We observed that the HPV8 early region gene E6 specifically caused Lrig1+ hair follicle junctional zone KSC proliferation and expansion, which would facilitate viral transmission. Within Lrig1+ KSCs specifically, HPV8 E6 bound intracellular p300 to phosphorylate the STAT3 transcriptional regulatory node. This induced ΔNp63 expression, resulting in KSC expansion into the overlying epidermis. HPV8 was associated with 70% of human actinic keratoses. Together, these results define the "hit-and-run" mechanism for HPV8 in human actinic keratosis as an expansion of KSCs, which lack melanosome protection and are thus susceptible to sun light-induced malignant transformation.
Subject(s)
Cell Proliferation , Keratinocytes , Keratosis, Actinic , Oncogene Proteins, Viral , Papillomavirus Infections , STAT3 Transcription Factor , Stem Cells , STAT3 Transcription Factor/metabolism , Keratinocytes/virology , Keratinocytes/metabolism , Keratinocytes/pathology , Humans , Keratosis, Actinic/pathology , Keratosis, Actinic/metabolism , Keratosis, Actinic/virology , Animals , Mice , Stem Cells/metabolism , Stem Cells/virology , Oncogene Proteins, Viral/metabolism , Oncogene Proteins, Viral/genetics , Papillomavirus Infections/virology , Papillomavirus Infections/pathology , Papillomavirus Infections/metabolism , Papillomavirus Infections/complications , Disease Models, Animal , FemaleABSTRACT
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.
Subject(s)
Keratosis, Actinic , Humans , Keratosis, Actinic/epidemiology , Keratosis, Actinic/therapy , Skin Neoplasms/epidemiology , Skin Neoplasms/prevention & control , Skin Neoplasms/etiology , Skin Neoplasms/pathology , Risk Factors , PrevalenceABSTRACT
Topical tirbanibulin is a highly effective and well tolerated novel treatment option for actinic keratoses (AKs). This study aimed to characterize the mode of action of tirbanibulin in keratinocytes (NHEK) and cutaneous squamous cell carcinoma (cSCC) cell lines (A431, SCC-12) in vitro. Tirbanibulin significantly reduced proliferation in a dose-dependent manner in all investigated cell lines, inhibited migration, and induced G2/M-cell cycle arrest only in the cSCC cell lines analyzed, and induced apoptosis solely in A431, which showed the highest sensitivity to tirbanibulin. In general, we detected low basal expression of phosphorylated SRC in all cell lines analyzed, therefore, interference with SRC signaling does not appear to be the driving force regarding the observed effects of tirbanibulin. The most prominent tirbanibulin-mediated effect was on ß-tubulin-polymerization, which was especially impaired in A431. Additionally, tirbanibulin induced an increase of the proinflammatory cytokines IL-1α, bFGF and VEGF in A431. In conclusion, tirbanibulin mediated anti-tumor effects predominantly in A431, while healthy keratinocytes and more dedifferentiated SCC-12 were less influenced. These effects of tirbanibulin are most likely mediated via dysregulation of ß-tubulin-polymerization and may be supported by proinflammatory aspects.
Subject(s)
Apoptosis , Carcinoma, Squamous Cell , Cell Movement , Cell Proliferation , Keratinocytes , Skin Neoplasms , Tubulin , Humans , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Keratinocytes/drug effects , Keratinocytes/metabolism , Cell Line, Tumor , Tubulin/metabolism , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Skin Neoplasms/metabolism , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Movement/drug effects , Antineoplastic Agents/pharmacology , Polymerization/drug effects , Keratosis, Actinic/drug therapy , Keratosis, Actinic/pathology , Keratosis, Actinic/metabolism , Signal Transduction/drug effects , Acetamides , Morpholines , PyridinesSubject(s)
Keratosis, Actinic , Humans , Keratosis, Actinic/epidemiology , Keratosis, Actinic/pathology , Female , Male , Aged , Incidence , Middle Aged , Aged, 80 and over , Age Factors , Sex Factors , AdultABSTRACT
Clinical grading of actinic keratosis (AK) is based on skin surface features, while subclinical alterations are not taken into consideration. Dynamic optical coherence tomography (D-OCT) enables quantification of the skin´s vasculature, potentially helpful to improve the link between clinical and subclinical features. We aimed to compare microvascular characteristics across AK grades using D-OCT with automated vascular analysis. This explorative study examined AK and photodamaged skin (PD) on the face or scalp. AKs were clinically graded according to the Olsen Classification scheme before D-OCT assessment. Using an open-source software tool, the OCT angiographic analyzer (OCTAVA), we quantified vascular network features, including total and mean vessel length, mean vessel diameter, vessel area density (VAD), branchpoint density (BD), and mean tortuosity from enface maximum intensity projection images. Additionally, we performed subregional analyses on selected scans to overcome challenges associated with imaging through hyperkeratosis (each lesion group; n = 18). Our study included 45 patients with a total of 205 AKs; 93 grade I lesions, 65 grade II, 47 grade III and 89 areas with PD skin. We found that all AK grades were more extensively vascularized relative to PD, as shown by greater total vessel length and VAD (p ≤ 0.009). Moreover, AKs displayed a disorganized vascular network, with higher BD in AK I-II (p < 0.001), and mean tortuosity in AK II-III (p ≤ 0.001) than in PD. Vascularization also increased with AK grade, showing significantly greater total vessel length in AK III than AK I (p = 0.029). Microvascular quantification of AK unveiled subclinical, quantitative differences among AK grades I-III and PD skin. D-OCT-based microvascular assessment may serve as a supplement to clinical AK grading, potentially raising perspectives to improve management strategies.
Subject(s)
Keratosis, Actinic , Skin , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Keratosis, Actinic/diagnostic imaging , Keratosis, Actinic/pathology , Keratosis, Actinic/diagnosis , Male , Female , Aged , Middle Aged , Skin/diagnostic imaging , Skin/pathology , Skin/blood supply , Severity of Illness Index , Aged, 80 and over , Scalp/pathology , Scalp/diagnostic imaging , Skin Aging/pathology , Face/diagnostic imagingABSTRACT
Actinic keratosis (AK) is a common precancerous condition found on sun-damaged skin. Tirbanibulin 1 % ointment has been approved for the topical treatment of non-hyperkeratotic facial and scalp Olsen grade I AKs over a contiguous area of 25 cm2 with a daily application for 5 consecutive days. Our aim was to investigate the use of in vivo RCM in the assessment of the response of AKs treated with tirbanibulin, as it has never been described in the published Literature. A total of 10 AKs in 10 consecutive outpatients were enrolled in the present study in May 2023. The follow-up visit was scheduled after 30 days from last application of tirbanibulin ointment. At follow-up visit, a complete response was described by clinical, dermoscopic and in vivo RCM examination in 10 out of 10 lesions, with a recovery of stratum corneum, decrease in atypical honeycomb pattern and changes in dermal collagen. All patients were followed up for at least 8 months and further recurrences were not registered. Based on our experience, we confirm the efficacy and safety of tirbanibulin in treating AKs and the usefulness of RCM in vivo examination for the therapeutic monitoring of such lesions, even in a very early stage.
Subject(s)
Keratosis, Actinic , Microscopy, Confocal , Humans , Keratosis, Actinic/drug therapy , Female , Male , Aged , Microscopy, Confocal/methods , Middle Aged , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Aged, 80 and over , Photochemotherapy/methodsSubject(s)
Aminolevulinic Acid , Keratosis, Actinic , Photochemotherapy , Humans , Keratosis, Actinic/drug therapy , Aminolevulinic Acid/therapeutic use , Photochemotherapy/methods , Prospective Studies , Male , Female , Middle Aged , Aged , Photosensitizing Agents/therapeutic use , East Asian PeopleABSTRACT
We aimed to unveil the underlying pathogenic mechanisms of skin cancer in relation to metabolic factors and pathway mechanisms. This study utilized the TwoSample Mendelian randomization (MR) method to investigate the causal relationship between 1400 plasma metabolites and skin cancer. The primary method employed was the inverse variance weighting (IVW). Through IVW analysis, we found 105 plasma metabolites associated with Basal Cell Carcinoma (BCC), with the highest association observed for Prolylglycine levels (OR [95% CI]: 1.1902 [1.0274, 1.3788]). For Malignant Melanoma of Skin (MSS), 68 plasma metabolites were linked, with the highest causal relationship seen for 3-Hydroxybutyrate levels (OR [95% CI]: 1.0030 [1.0013, 1.0048]). Regarding actinic keratosis (AK), and the highest association observed for Hexadecadienoate (16:2n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.7125]). Glycerol to palmitoylcarnitine (16: n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.125]) were found to be significant for BCC and AK. Palmitoylcarnitine (C16) had the most positive causal effect for BCC (OR [95% CI]: 1.1777 [1.0493, 1.3218]), while 5-hydroxy-2-methylpyridine sulfate levels had the highest effect for AK (OR [95% CI]: 1.1788 [1.0295, 1.3498]). And 4-guanidinobutanoate levels had the largest positive causal effect (OR [95% CI]: 1.0857 [1.0417, 1.1317]) for BCC, and X-11880 levels for MSS (OR [95% CI]: 1.0013 [1.0000, 1.0025]). The study revealed a positive association between hereditary Glycerol to palmitoylcarnitine (C16) and 5-hydroxy-2-methylpyridine sulfate levels with the risk of developing BCC and AK. Additionally, 4-guanidinobutanoate levels and X 11880 levels were found to be positively associated with the risk of BCC and MMS.
Subject(s)
Carcinoma, Basal Cell , Mendelian Randomization Analysis , Skin Neoplasms , Humans , Skin Neoplasms/blood , Skin Neoplasms/genetics , Skin Neoplasms/epidemiology , Carcinoma, Basal Cell/blood , Carcinoma, Basal Cell/genetics , Carcinoma, Basal Cell/epidemiology , Melanoma/blood , Melanoma/genetics , Melanoma/epidemiology , Keratosis, Actinic/blood , Keratosis, Actinic/genetics , 3-Hydroxybutyric Acid/blood , Genetic Predisposition to Disease , Melanoma, Cutaneous MalignantABSTRACT
BACKGROUND: 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. 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. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<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%). CONCLUSIONS: 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.
Subject(s)
Keratosis, Actinic , Patient Reported Outcome Measures , Patient Satisfaction , Quality of Life , Humans , Keratosis, Actinic/drug therapy , Keratosis, Actinic/diagnosis , Male , Female , United States , Aged , Middle Aged , Treatment Outcome , Aged, 80 and over , Administration, Cutaneous , Ointments , Follow-Up Studies , Adult , Surveys and Questionnaires/statistics & numerical dataABSTRACT
BACKGROUND: Chronic inflammation has been shown to promote cancer progression. Rosacea is indeed a long-term inflammatory skin condition and had been reported to link with increased risk for several types of malignancies, but evidence for causality is lacking. OBJECTIVES: To systematically estimate the causal relationship between rosacea and several types of cancer, including cutaneous malignant melanoma (CMM), cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), actinic keratosis (AK), thyroid cancer, breast cancer, glioma and hepatic cancer, as well as explore the potential underlying pathogenesis. METHODS: We conducted a bidirectional two-sample Mendelian randomization study to probe the potential causal relationships between rosacea and several types of cancer. Instrumental variables were established using genome-wide significant single nucleotide polymorphisms associated with rosacea and cancers. The assessment of causality was carried out through multiple methods, and the robustness of the results was evaluated via sensitivity analyses. RESULTS: There was no significant indication of causal effects of rosacea on CMM (pivw = 0.71), cSCC (pivw = 0.45), BCC (pivw = 0.90), AK (pivw = 0.73), thyroid cancer (pivw = 0.59), glioma (pivw = 0.15), and hepatic cancer (pivw = 0.07), but the genetic risk of rosacea was associated with an increased susceptibility to human epidermal growth factor receptor (HER)-negative malignant neoplasm of breast (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.18; pivw = 0.01). TANK (TRAF family member associated nuclear factor kappa B (NFKB) activator) was identified as a common protective gene for both rosacea (OR, 0.90; 95% CI, 0.82-0.99; pivw = 0.048) and HER-negative malignant neoplasm of the breast (OR, 0.86; 95% CI, 0.75-0.98; pivw = 0.032), which was primarily enriched in the negative regulation of NF-κB signal transduction and may contribute to the genetic links between rosacea and this subtype of breast cancer. CONCLUSIONS: Our findings provide suggestive evidence for causal links between rosacea and HER-negative malignant neoplasm of the breast risk.
Subject(s)
Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Rosacea , Skin Neoplasms , Humans , Rosacea/genetics , Skin Neoplasms/genetics , Female , Melanoma/genetics , Carcinoma, Basal Cell/genetics , Carcinoma, Squamous Cell/genetics , Risk Factors , Genetic Predisposition to Disease/genetics , Breast Neoplasms/genetics , Keratosis, Actinic/genetics , Thyroid Neoplasms/genetics , Glioma/genetics , Liver Neoplasms/genetics , MaleABSTRACT
Simulated daylight photodynamic therapy is a relatively new and potentially less painful alternative to conventional red light photodynamic therapy for actinic keratosis. Qualitative research exploring patient experiences of pain and skin reactions during these treatments is scarce. To address this, semi-structured interviews were conducted of 10 patients aged 60-81 years with symmetrically distributed actinic keratoses 4 weeks after split-face treatment with conventional red light photodynamic therapy and simulated daylight photodynamic therapy. The participants were recruited from an ongoing clinical randomized trial. Interviews (median length 35 min) were conducted between June 2022 and January 2023, audio-recorded, transcribed verbatim, and analysed qualitatively using content analysis, as described by Graneheim and Lundman. Participants reported that conventional red light photodynamic therapy was very painful during illumination and transiently painful in the post-treatment period, while simulated daylight photodynamic therapy was almost painless during illumination and led to minor post-treatment pain. Also, skin reactions were more intense and longer-lasting with conventional red light photodynamic therapy than with simulated daylight photodynamic therapy. Most participants expressed a treatment preference for simulated daylight photodynamic therapy but had reservations about its unestablished long-term effectiveness. This study underscores the considerable pain associated with conventional red light photodynamic therapy, and the pivotal importance of shared decision-making when selecting the most appropriate treatment.
Subject(s)
Keratosis, Actinic , Photochemotherapy , Humans , Aminolevulinic Acid , Keratosis, Actinic/diagnosis , Keratosis, Actinic/drug therapy , Pain/diagnosis , Pain/etiology , Pain/drug therapy , Photochemotherapy/adverse effects , Photosensitizing Agents/adverse effects , Red Light , Treatment OutcomeABSTRACT
BACKGROUND: Actinic keratosis (AK) is a precancerous lesion that occurs in areas that are chronically exposed to sunlight and has the potential to develop into invasive cutaneous squamous cell carcinoma (cSCC). We investigated the efficacy of 20 % 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) with LED red light for the treatment of AK in Chinese patients by examining changes in dermoscopic features, histopathology and fluorescence after treatment. METHODS: Twenty-eight patients with fourty-six AK lesions from March 2022 to September 2023 were treated with 20 % ALA, and 3 h later, they were irradiated with LED red light (80-100 mW/cm2) for 20 min. A session of 20 % ALA-PDT was performed once a week for three consecutive weeks, and the dermoscopic, histopathological, fluorescent and photoaging outcomes were measured one week after the treatment. RESULTS: One week after ALA-PDT, complete remission (CR) was reached in 53.6 % of patients. The CR of Grade I AK lesions was 100 %, that of Grade II lesions was 71.4 %, and that of Grade III lesions was 38.1 %. There was a significant improvement in the dermoscopic features, epidermal thickness and fluorescence of the AK lesions. The presence of red fluorescence decreased, and there was an association between CR and post-PDT fluorescence intensity. ALA-PDT also exhibited efficacy in treating photoaging, including fine lines, sallowness, mottled pigmentation, erythema, and telangiectasias, and improved the global score for photoaging. There were no serious adverse effects during or after ALA-PDT, and 82.1 % of the patients were satisfied with the treatment. CONCLUSION: AK lesions can be safely and effectively treated with 20 % ALA-PDT with LED red light, which also alleviates photoaging in Chinese patients, including those with multiple AKs. This study highlights the possibility that fluorescence could be used to diagnose AK with peripheral field cancerization and evaluate the efficacy of ALA-PDT.
Subject(s)
Aminolevulinic Acid , Keratosis, Actinic , Photochemotherapy , Photosensitizing Agents , Keratosis, Actinic/drug therapy , Aminolevulinic Acid/therapeutic use , Aminolevulinic Acid/pharmacology , Humans , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Female , Male , Aged , Middle Aged , Dermoscopy/methods , Aged, 80 and over , FluorescenceABSTRACT
One of the most common forms of cancer in fair skinned populations is Non-Melanoma Skin Cancer (NMSC), which primarily consists of Basal Cell Carcinoma (BCC), and cutaneous Squamous Cell Carcinoma (SCC). Detecting NMSC early can significantly improve treatment outcomes and reduce medical costs. Similarly, Actinic Keratosis (AK) is a common skin condition that, if left untreated, can develop into more serious conditions, such as SCC. Hyperspectral imagery is at the forefront of research to develop non-invasive techniques for the study and characterisation of skin lesions. This study aims to investigate the potential of near-infrared hyperspectral imagery in the study and identification of BCC, SCC and AK samples in comparison with healthy skin. Here we use a pushbroom hyperspectral camera with a spectral range of ≈ 900 to 1600 nm for the study of these lesions. For this purpose, an ad hoc platform was developed to facilitate image acquisition. This study employed robust statistical methods for the identification of an optimal spectral window where the different samples could be differentiated. To examine these datasets, we first tested for the homogeneity of sample distributions. Depending on these results, either traditional or robust descriptive metrics were used. This was then followed by tests concerning the homoscedasticity, and finally multivariate comparisons of sample variance. The analysis revealed that the spectral regions between 900.66-1085.38 nm, 1109.06-1208.53 nm, 1236.95-1322.21 nm, and 1383.79-1454.83 nm showed the highest differences in this regard, with <1% probability of these observations being a Type I statistical error. Our findings demonstrate that hyperspectral imagery in the near-infrared spectrum is a valuable tool for analyzing, diagnosing, and evaluating non-melanoma skin lesions, contributing significantly to skin cancer research.