Refusal of Retreatment With Topical 5-Fluorouracil Among Patients With Actinic Keratosis: Qualitative Analysis.

BACKGROUND: Actinic keratosis (AK) is a common premalignant skin lesion, and topical 5-fluorouracil (5-FU) is commonly used in field-directed therapy. However, 5-FU is associated with frequent local skin reactions. OBJECTIVE: This study aimed to qualitatively assess experiences among patients with AK who refuse retreatment with 5-FU. METHODS: Semistructured interviews were conducted with 10 adult participants who had received treatment with 5-FU for AK between January 1, 2017, and January 1, 2020, and refused future treatment with 5-FU. Results were analyzed using qualitative research methods. RESULTS: Although most participants had low concern upon having received a diagnosis of AK, most felt that treatment is very important. When initiating treatment with 5-FU, most cited recommendation by their health care professionals as the primary motivator and initially had low concern regarding treatment. The side effects associated with treatment were physically and psychosocially burdensome for most participants and led to temporary lifestyle adjustments. After treatment, most did not believe that their health care provider prepared them for treatment or were unsure. While half of the participants felt that 5-FU helped treat AKs, half were either unsure, due to premature discontinuation, or did not think that 5-FU treated their AKs. CONCLUSIONS: 5-FU is one of the most commonly prescribed treatments for AKs, yet most patients experienced both a physical and psychosocial burden with the treatment. Inability to assess efficacy due to premature discontinuation secondary to 5-FU-related reactions is common, and shared decision-making, navigating treatment options, and taking into account patient preferences may be critical to help assure better adherence and outcomes. Although our study was limited by input from participants who refused future treatment with 5-FU, most stated that they would still continue to seek treatment for AKs in the future and would consider other topical treatments, especially if associated with a milder tolerability profile.

Efficacy and safety of a thermal fractional skin rejuvenation system (Tixel) for the treatment of facial and/or scalp actinic keratoses.

Actinic keratoses are common cutaneous lesions with a potential to progress to invasive squamous cell carcinoma. Therefore, treatment is crucial. The Tixel® is a noninvasive thermomechanical device designed to transfer heat to the upper dermis in a controlled manner according to a predetermined setting. This study aimed to evaluate the safety and efficacy of a thermomechanical fractional skin resurfacing technology for the treatment of facial and scalp actinic keratoses. A prospective, open-label, before-after study was conducted in a tertiary medical centre from May 2020 to April 2021. Patients presenting with facial/scalp actinic keratoses of mild-to-moderate thickness underwent 2 or 3 Tixel treatments (depending on clinical improvement), 3-4 weeks apart. The reduction in lesion count and overall improvement in appearance were assessed by clinical examination and digital photography. Findings were compared between baseline and follow-up at 3 months after the last treatment session. Patient satisfaction was evaluated by questionnaire, and adverse effects were documented. A total of 20 patients participated in the study. All completed 2-3 treatments and follow-up visits. Assessment of digital photographs was performed by 2 assessors blinded to the timepoint at which each photo was taken (before or after treatment). The average number of lesions at baseline was 9.8 (± 4.8) and the mean reduction in lesion count was 7.9 (± 4.4) (80.6%). Complete clearance was observed in 31.6% of patients. No adverse effects were noted during treatment and follow-up. Most patients reported being "very satisfied" or "satisfied" with the treatment results (85%) and experience (95%). Treating facial and scalp actinic keratoses with the Tixel device was found to be effective and safe.

Japanese Dermatological Association Guidelines: Outlines of Guidelines for Cutaneous Squamous Cell Carcinoma 2020.

In consideration of the development of treatment options for squamous cell carcinoma (SCC), the Japanese Skin Cancer Society issued the first guidelines of SCC in 2007 and revised them in 2015. Here, we report the English version of the 2020 edition of the Japanese SCC guidelines. The first half of this article is an overview of SCC including actinic keratosis and Bowen's disease, and the second half discusses three clinical questions: (i) treatment of actinic keratosis; (ii) determination of the resection margin of the primary lesion; and (iii) treatment of radically incurable cases, as contemporary problems encountered in treating SCC. In these evaluations, all processes were implemented according to the Grading of Recommendations, Assessment, Development, Evaluation system. Also, items of recommendation concerning each clinical question were determined by a multidisciplinary expert panel consisting of dermatologists, plastic/reconstructive surgeons, radiologists, and oncologists through a comprehensive literature search and systematic reviews.

Japanese Dermatological Association Guidelines: outlines of guidelines for cutaneous squamous cell carcinoma 2020

In consideration of the development of treatment options for squamous cell carcinoma (SCC), the Japanese Skin Cancer Society issued the first guidelines of SCC in 2007 and revised them in 2015. Here, we report the English version of the 2020 edition of the Japanese SCC guidelines. The first half of this article is an overview of SCC including actinic keratosis and Bowen's disease, and the second half discusses three clinical questions: (i) treatment of actinic keratosis; (ii) determination of the resection margin of the primary lesion; and (iii) treatment of radically incurable cases, as contemporary problems encountered in treating SCC. In these evaluations, all processes were implemented according to the Grading of Recommendations, Assessment, Development, Evaluation system. Also, items of recommendation concerning each clinical question were determined by a multidisciplinary expert panel consisting of dermatologists, plastic/reconstructive surgeons, radiologists, and oncologists through a comprehensive literature search and systematic reviews.

A Critical Appraisal of Evidence- and Consensus-Based Guidelines for Actinic Keratosis.

Actinic keratoses (AK) are common lesions of the skin that can be effectively treated with several lesion- and field-directed treatments. Clinical practice guidelines assist physicians in choosing the appropriate treatment options for their patients. Here, we aimed to systematically identify and evaluate the methodological quality of currently available guidelines for AK. Guidelines published within the last 5 years were identified in a systematic search of guideline databases, Medline and Embase. Then, six independent reviewers evaluated the methodological quality using the tools "Appraisal of Guidelines for Research and Evaluation" (AGREE II) and "Recommendation EXcellence" (AGREE-REX). The Kruskal-Wallis (H) test was used to explore differences among subgroups and Spearman's correlation to examine the relationship between individual domains. Three guidelines developed by consortia from Canada, Germany and the United Kingdom were eligible for the evaluation. The German guideline achieved the highest scores, fulfilling 65 to 92% of the criteria in AGREE II and 67 to 84% in AGREE-REX, whereas the Canadian guideline scored 31 to 71% of the criteria in AGREE II and 33 to 46% in AGREE-REX. The domains "stakeholder involvement" and "values and preferences" were identified as methodological weaknesses requiring particular attention and improvement in future guideline efforts.

Reflectance confocal microscopy in actinic keratosis-Comparison of efficacy between cryotherapy protocols.

BACKGROUND: Actinic keratosis (AK) incidence is increasing. Due to the risk of progression to squamous cell carcinoma, early detection and treatment are essential. The method stated in the European Consensus is cryotherapy, but there is no standard protocol defined for better results. OBJECTIVES: To compare two different cryotherapy protocols for AK using reflectance confocal microscopy (RCM) as a noninvasive imaging method for evaluation. METHODS: A self-controlled clinical trial was proposed to compare the efficacy of cryotherapy in two different application protocols. Grade II AKs in the forearms were submitted to freezing and thawing time of 10 seconds for 1 cycle (group A) or 2 cycles (group B). At baseline and 4 weeks after treatment, the same dermatologists assessed RCM evaluation (thickness of horny layer, parakeratosis, dyskeratosis, atypia in spinous layer, fibrosis, and presence of inflammatory cells in epidermis and dermis). RESULTS: We examined 24 AK lesions in each group. Statistical evaluation of the results evidenced superior response after 2 cycles of cryotherapy in parakeratosis and number of inflammatory cells in epidermis. CONCLUSION: Both protocols are effective in clearing clinical AK. Two cycles are not generating more side effects (fibrosis) and could reduce the risk of recurrence (better "clearance" of parakeratosis).

Dynamic thermal imaging on actinic keratosis patients: A preliminary study.

BACKGROUND: Diagnosis of actinic keratosis (AK) based only on clinical findings can be misleading, and histopathological diagnosis results in scars. Dynamic thermal imaging is a potential non-invasive tool for the diagnosis of AK. This imaging technique quantifies the infrared (IR) radiation emitted by a subject after exposure to external thermal stimuli, such as heat or cold. METHODS: Twenty-six histopathologically confirmed AK patients participated in the study. We compared the dynamic thermal images of AK lesions and normal skin (control sites). Temperature changes were plotted as a thermal response graph. After fitting exponential curves to the thermal response graph, the curve was converted to a logarithmic form. RESULTS: Comparison of the early thermal response graphs of lesions and control sites showed faster thermal recovery of AK lesions. There was a significant difference in the gradient component of the calculated logarithmic equation between the AK lesions and control sites (P < 0.001). CONCLUSION: Dynamic thermal imaging can be used as an auxiliary diagnostic tool for AK.

Laser-assisted photodynamic therapy for actinic keratosis: A systematic review and meta-analysis.

BACKGROUND: Photodynamic therapy (PDT) is an effective intervention for actinic keratosis and field cancerization. Ablative fractional lasers may facilitate the delivery of photosensitizers and thereby improve the effects of PDT. OBJECTIVE: To summarize the current evidence on the efficacy and safety of laser-assisted PDT. METHODS: We performed a systematic literature research in Medline, Embase, and the Cochrane Central Register of Controlled Trials and hand-searched pertinent trial registers for eligible randomized controlled trials. Results from individual studies were pooled by using a random-effects model. The risk of bias was estimated with the Cochrane Risk of Bias Tool, and the quality of evidence of the outcomes was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Of 817 records initially identified, 7 randomized controlled trials were included in the qualitative analysis and 4 were included in the meta-analysis. Laser-assisted PDT showed significantly higher clearance rates than did PDT monotherapy (risk ratio, 1.33; 95% confidence interval, 1.24-1.42; I2 = 25%; P < .01). There was no difference in pain intensity between laser-assisted PDT and other interventions (mean difference, 0.31; 95% confidence interval, -0.12 to 0.74; I2 = 0%; P = .16). The included studies showed a high risk of bias. LIMITATIONS: The clinical heterogeneity of included studies. CONCLUSION: Laser-assisted PDT is more efficient but not more painful than PDT or laser treatment only.

Occurrence of squamous cell carcinoma in Milchschaf sheep in Uruguay / Ocorrência do carcinoma de células escamosas em ovinos Milchschaf em Uruguai

ABSTRACT: In this study, the epidemiological and pathological features of an outbreak of squamous cell carcinoma (SCC) in adult female sheep and a young ram, Friesian Milchschaf breed or crossbreed is described. Seven adult females belonging to an original flock nucleus of 20 animals were affected, as well as a young ram belonging to the same nucleus was affected in other establishment. Multiple verrucous neoplastic masses of several months of evolution were evident in the head region, with local invasion and regional lymph node metastases. Histological studies revealed a cancerous stage of invasion of the dermis and neoplastic proliferation characteristic of invasive SCC, and a pre-cancerous stage with solar elastosis and chronic solar keratosis lesions induced by sunlight. Decrease in latitude, increased level of solar radiation with long exposure to sunlight, and the phenotypic characteristics of the breed are the main factors responsible for the high prevalence of SCC, showing the susceptibility of the Friesian Milchschaf breed and crossbreed in temperate zones as Uruguay.

RESUMO: Neste estudo descrevem-se as características epidemiológicas e patológicas de um surto de carcinoma de células escamosas (SCC) em ovelhas adultas e ram jovem, raça Friesian Milchschaf ou cruza. Foram afetadas sete fêmeas adultas pertencentes a um núcleo de rebanho original de 20 animais, bem como um ram jovem pertencente ao mesmo núcleo em que foi afetado em outro estabelecimento. Múltiplas neoplásicas verrucosas de vários meses de evolução foram evidentes na região principal, com invasão local e metástases de linfonodos regionais. Estudos histológicos revelaram um estágio cancerígeno de invasão da derme e proliferação neoplásica característica do SCC invasivo e um estágio pré-cancerígeno com elastose solar e lesões de ceratose solar crônica induzidas pela luz solar. A diminuição da latitude, o aumento do nível de radiação solar com longa exposição à luz solar e as características fenotípicas da raça são os principais fatores responsáveis pela alta prevalência de SCC, mostrando a susceptibilidade da raça Friesian Milchschaf e cruzada em zonas temperadas como o Uruguai.

Comparison of the Treatment Guidelines for Actinic Keratosis: A Critical Appraisal and Review.

There are currently several reputable guidelines on the treatment of actinic keratosis (AK) from groups in Canada, the United Kingdom, and Europe. These recommendations, based on evidence or expert consensus, offer clinicians a variety of treatment options for the different clinical presentations of AKs. Although the guidelines are similar in some regards, variations exist in treatment options, duration, and strength of recommendation. Some guidelines also lack input on specific therapies and certain types of AK, such as hypertrophic or thin presentations. The purpose of this article is to review and compare guidelines published by Canadian, UK, and European groups for the management of AKs in patients.

Use of Lesion Response Rate in Actinic Keratosis Trials.

Complete patient clearance is often required by regulatory agencies for the approval of treatments for actinic keratosis (AK). However, an increasing number of clinicians have challenged the use of this measure in clinical practice and its interpretation. It has been argued that complete patient clearance often underestimates the clinical benefit of a drug and is influenced by a number of key confounding factors, such as number and distribution of lesions, at baseline. Lesions response rate is one alternative which has been suggested as more relevant due to its applicability to clinical practice and closer reflection of the clinical value of the drug. This paper provides an updated perspective on the topic and details the current thinking on the role of complete clearance and lesion response rate in the context of AK. FUNDING: Galderma.

Consensus recommendations on the use of daylight photodynamic therapy with methyl aminolevulinate cream for actinic keratoses in Australia.

Australia has the highest prevalence of actinic keratoses (AK) worldwide. Because of the risk of transformation of AK to invasive squamous cell carcinomas, consensus guidelines recommend that AK are removed using appropriate therapies to prevent progression to invasive disease. Daylight photodynamic therapy (PDT) is emerging as an efficacious treatment for AK, particularly for patients who require treatment of large areas of chronic actinic damage that can be exposed easily to daylight. Daylight PDT with methyl aminolevulinate (MAL) cream is a simple treatment for AK, almost painless, well tolerated and convenient, requiring minimal time in the clinic. Randomised controlled studies from northern Europe and Australia support the use of daylight PDT as an effective therapy for grade I and II AK on the face and scalp. There is sufficient daylight to conduct daylight PDT in Australia at any time of the year and during most weather conditions. Hence, daylight PDT with MAL can be included as an effective and well-tolerated new treatment option for the treatment of AK in Australia. These consensus recommendations provide guidelines for Australian clinicians on the use of daylight PDT in the treatment of diagnosed AK.

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

A histopathological study of melanocytic and pigmented skin lesions in patients with albinism.

BACKGROUND: Oculocutaneous albinism (OCA) is a group of genetic disorders characterized by diminished pigmentation of the skin, hair and eyes. Individuals with OCA are at increased risk to develop sun-induced skin malignancies. The incidence of malignant melanoma in OCA individuals is, however, very low. The aim of this study was to document pigmented and melanocytic skin lesions occurring in patients with OCA. METHODS: A prospective study was performed. Sixteen patients with OCA presenting at the Oncology and Dermatology Departments at Universitas Academic Hospital Annex in Bloemfontein, South Africa, were included. Selected clinically pigmented and/or melanocytic lesions were biopsied and studied by light microscopy. RESULTS: Twenty-four punch biopsies were taken. Ten dendritic freckles and 10 melanocytic nevi were confirmed histologically. The nevi, which occurred in eight patients, were found on sun-protected skin. All the freckles occurred on sun-exposed skin. Twelve patients had current or previous skin malignancies. No melanomas were present in the study population. Other skin lesions ranged from solar keratoses to squamous cell carcinomas. CONCLUSION: The majority of pigmented lesions were dendritic freckles that occurred on sun-exposed skin. None of the patients had a current or previous diagnosis of malignant melanoma.

p53 immunoexpression in stepwise progression of cutaneous squamous cell carcinoma and correlation with angiogenesis and cellular proliferation.

Multistep carcinogenesis involves loss of function of tumor suppressor proteins such as p53 and induction of angiogenesis. Such mechanisms contribute to cutaneous squamous cell carcinoma progression and may be interconnected. We aimed to explore p53 immunoexpression in spectral stages of cutaneous squamous cell carcinoma and correlate expression to both neovascularization and cellular proliferation. We estimated the percentages of immunostained cells for p53 and Ki67 (proliferation marker) in three groups: 23 solar keratoses, 28 superficially invasive squamous cell carcinomas and 28 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by neoangiogenesis (CD105) immunomarker in each group. There was no significant difference for rate of p53- and Ki67-positive cells between groups. Significant positive correlation was found between the CD105 microvascular area and the rate of p53 positive cells in superficially invasive squamous cell carcinoma as well as between the rate of p53- and Ki67-positive cells in invasive squamous cell carcinoma. p53 and Ki67 immunoexpression did not increase with cutaneous squamous cell carcinoma progression. Neovascularization in the initial stage of invasion and proliferative activity in the frankly invasive stage were both associated with p53 immunoexpression. Loss of p53 tumor suppressor function through progressive steps may be directly involved in skin carcinogenesis.

Reliability of solar keratosis clinical diagnosis: A prospective study.

Usually solar keratoses (SK) are diagnosed clinically. However other diseases may clinically present as erythematous macules, papules or patches on sun-exposed areas; therefore the histopathology remains the gold standard diagnostic tool. Our study, which assessed the efficacy of photodynamic therapy (PDT), showed that one in 20 clinically diagnosed SK lesions grade I-II identified by board-certified dermatologists were rosacea and only one in 40 were malignant lesions. These findings should be considered by clinicians who treat clinically diagnosed grade I-II SK without response to treatment or diagnose the recurrence of SK after PDT.

The efficacy and safety of topical 5% 5-fluorouracil in renal transplant recipients for the treatment of actinic keratoses.

Actinic keratoses (AK) occur more commonly and behave more aggressively in renal transplant recipients (RTR). Topical 5% 5-fluorouracil (5-FU) cream is a commonly used agent whose efficacy and safety have never been exclusively studied in the RTR population before. Eight RTR were enrolled and 5% 5-FU cream applied to AK lesions on their face twice daily for 3 weeks. They were reviewed at 2 and 8 weeks, and 12 months post-commencement of treatment. Their AK were counted and their cumulative surface areas measured. Patients completed surveys monitoring adverse effects and tolerability. Complete (100%) and partial clearance (≥ 75%) rates were measured, as well as mean percentages of the reduction in AK surface area. Patients had complete clearance rates of 63 and 0% at 8 weeks and 12 months, respectively. All (100%) patients had partial clearance at week 8 and 71% had partial clearance at 12 months. Patients had on average 15 AK at week 0 and 1 and 3 at 8 weeks and 12 months, respectively. The mean AK clearance rate was 98% at week 8 and 79% at 12 months. Common side-effects were erythema, itch and flaking or scaling, mostly mild in severity. 5-FU appears to be an efficacious and safe treatment for AK in RTR.

5% fluorouracil chemowraps in the management of widespread lower leg solar keratoses and squamous cell carcinoma.

Elderly patients with extensive hypertrophic solar keratoses and squamous cell carcinoma on the lower legs can pose significant management challenges. Typically these patients require surgical treatment which is complicated by comorbidities and poor background lower leg skin. 5% fluorouracil chemowraps provides a useful alternative technique for the management of diffuse hypertrophic solar keratoses and as an adjuvant, and in some situations as a palliative treatment, for squamous cell carcinomas on the lower legs.