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Gracia-Cazaña T, Gilaberte Y. Home Self-Applied Daylight Photodynamic Therapy: Current Map in Spain and Management Proposals. ACTAS DERMO-SIFILIOGRAFICAS 2025:S0001-7310(25)00107-3. [PMID: 40057229 DOI: 10.1016/j.ad.2024.10.064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 09/22/2024] [Accepted: 10/14/2024] [Indexed: 03/29/2025] Open
Abstract
OBJECTIVE To determine the current practices of Spanish dermatologists performing home self-applied daylight photodynamic therapy (dPDT), and their experience with this treatment. METHODOLOGY We conducted a retrospective, multicenter, cross-sectional observational study with participation from 100 dermatologists from public and private Spanish hospitals. Their practices were collected through an online questionnaire and prepared based on a literature review, including experience, climatology, advantages, disadvantages and satisfaction with the self-applied dPDT. RESULTS A total of 38.4% of dermatologists have >5 years of experience using dPDT and 72.7% alternate consultation and home self-application. A total of 61.1% of dermatologists do not have specific protocols for self-application and 69.4% explain instructions to their patients personally. A total of 50% prefer to apply dPDT in months of greater solar activity and 70.8% recommend treatment during the morning. A total of 95.9% of the patients are satisfied or very satisfied with the treatment. MAIN CONCLUSIONS Self-applied dPDT is an effective and well-tolerated option to treat AK, especially in patients who adequately follow instructions and have family support. It is necessary to protocolize the self-applied dPDT to guarantee a greater safety and efficacy profile in the home application format.
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Affiliation(s)
- T Gracia-Cazaña
- Servicio de Dermatología, Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza, España.
| | - Y Gilaberte
- Servicio de Dermatología, Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza, España
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Vennila M, Senthil A, Bharanidharan T, Shahidha R, Wezhli MM, Manikandan A, Al-Dossary OM, ISSAOUI N. Structural characterization, electronic properties in solvents, Hirshfeld, topological and biological investigation on Imiquimod – An immunomodulator agent. J Photochem Photobiol A Chem 2024; 457:115917. [DOI: 10.1016/j.jphotochem.2024.115917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
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Paul S, Chen Y, Mohaghegh M. Analysis of Prevalence, Socioeconomic and Disease Trends of Non-Melanoma Skin Cancer in New Zealand from 2008 to 2022. J Epidemiol Glob Health 2024; 14:1012-1021. [PMID: 38842790 PMCID: PMC11442425 DOI: 10.1007/s44197-024-00250-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 05/22/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Skin cancer shows geographic and ethnic variation. New Zealand-with a predominantly fair-skinned populations, high UV indices and outdoor lifestyles-has high rates of skin cancer. However, population prevalence data is lacking. This study aimed to determine the demographics and socioeconomic disease trends of non-melanoma skin cancer prevalence in New Zealand from a large targeted-screening study. METHODS A targeted screening programme was conducted among 32,839 individuals, Fitzpatrick Skin Types I to IV in Auckland, New Zealand during the 2008-2022 period. This data was analyzed retrospectively. Linear regression models were used to assess statistical trends of skin cancer prevalence over time, along with associated factors that included demographics, disease trends and overall prevalence. RESULTS A total of 32,839 individuals were screened and 11,625 skin cancers were detected. 16,784 individuals were females who had 4,378 skin cancers. 16,055 individuals were males who had 5,777 skin cancers. 54 males and 65 females had multiple skin cancers. The article presents detailed descriptions of tumour types and subtypes detected, age groups, demographic and socioeconomic information. regarding the non-melanoma skin cancers detected. CONCLUSION Overall men have more non-melanoma skin cancer (NMSC) than females; however females develop more BCC on the lips. BCC is three times more common in the 31-50 age group, whereas SCC are significantly more prevalent after age 80. Prevalence of BCC has not changed over the 15-year timeframe of the study but SCC has increased. Older ages and higher incomes are associated with higher rates of NMSC in New Zealand.
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Affiliation(s)
- Sharad Paul
- Auckland University of Technology, 55 Wellesley Street East, Auckland, 1010, New Zealand.
- Skin Surgery Clinic, 271A Blockhouse Bay Road, Auckland, 0600, New Zealand.
| | - Yipan Chen
- Auckland University of Technology, 55 Wellesley Street East, Auckland, 1010, New Zealand
| | - Mahsa Mohaghegh
- Auckland University of Technology, 55 Wellesley Street East, Auckland, 1010, New Zealand
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Zhao HJ, Ushcatz I, Tadrous M, Aoki V, Chang AY, Levell NJ, Von Schuckmann L, Drucker AM. International time trends and differences in topical actinic keratosis therapy utilization. JAAD Int 2024; 16:18-25. [PMID: 38764482 PMCID: PMC11099316 DOI: 10.1016/j.jdin.2024.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2024] [Indexed: 05/21/2024] Open
Abstract
Background Actinic Keratoses (AK) are precancerous lesions that can lead to Squamous Cell Carcinoma. International differences in the utilization of topical medications to treat AK are not well described. Objectives To describe international differences in topical AK medication utilization, including associations of countries' economic status with AK medication utilization. Methods We used IQVIA MIDAS pharmaceutical sales data for 65 countries (42 high-income, 24 middle-income) from April 2011 to December 2021. We calculated each country's quarterly utilization of medications in grams per 1000 population. We used univariable linear regression to assess the association between country economic status and AK medication utilization. Results High-income countries used 15.37 more grams per 1000 population of 5-fluorouracil (95% CI: 9.68, 21.05), 4.64 more grams per 1000 population of imiquimod (95% CI: 3.45, 5.83), and 0.32 more grams per 1000 population of ingenol mebutate (95% CI: 0.05, 0.60). Limitations Missing medication utilization data for some countries. Conclusion High-income countries use more topical AK therapies than middle-income countries.
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Affiliation(s)
- Heather J. Zhao
- Department of Medicine, Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Inna Ushcatz
- Department of Medicine, Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Mina Tadrous
- Department of Medicine, Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
| | - Valeria Aoki
- Department of Dermatology, University of São Paulo School of Medicine, São Paulo, São Paulo Estado, Brazil
| | - Aileen Y. Chang
- Department of Dermatology, University of California, San Francisco, San Francisco, California
- Department of Dermatology, Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California
| | - Nick J. Levell
- Department of Dermatology, Norfolk and Norwich University Hospital, Norwich, UK
| | | | - Aaron M. Drucker
- Department of Medicine, Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada
- Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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Malvehy J, Stratigos AJ, Bagot M, Stockfleth E, Ezzedine K, Delarue A. Actinic keratosis: Current challenges and unanswered questions. J Eur Acad Dermatol Venereol 2024; 38 Suppl 5:3-11. [PMID: 38923589 DOI: 10.1111/jdv.19559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 09/29/2023] [Indexed: 06/28/2024]
Abstract
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.
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Affiliation(s)
- Josep Malvehy
- Hospital Clinic de Barcelona, IDIBAPS, and Spain & Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Universitat de Barcelona, Barcelona, Spain
| | | | - Martine Bagot
- Department of Dermatology, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, and Human Immunology, Pathophysiology and Immunotherapy, Institut National de la Santé et de la Recherche Médicale U976, Université de Paris, Paris, France
| | - Eggert Stockfleth
- Department of Dermatology, Ruhr University of Bochum, Bochum, Germany
| | - Khaled Ezzedine
- Department of Dermatology, Hôpital Henri Mondor, EA EpiDermE, UPEC-Université Paris-Est Créteil, Créteil, France
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Soare C, Cozma EC, Celarel AM, Rosca AM, Lupu M, Voiculescu VM. Digitally Enhanced Methods for the Diagnosis and Monitoring of Treatment Responses in Actinic Keratoses: A New Avenue in Personalized Skin Care. Cancers (Basel) 2024; 16:484. [PMID: 38339236 PMCID: PMC10854727 DOI: 10.3390/cancers16030484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/10/2024] [Accepted: 01/17/2024] [Indexed: 02/12/2024] Open
Abstract
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.
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Affiliation(s)
- Cristina Soare
- Department of Oncological Dermatology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.S.); (M.L.); (V.M.V.)
| | - Elena Codruta Cozma
- Department of Pathophysiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- Department of Dermatology and Allergology, Elias University Emergency Hospital, 011461 Bucharest, Romania;
| | - Ana Maria Celarel
- Department of Dermatology and Allergology, Elias University Emergency Hospital, 011461 Bucharest, Romania;
| | - Ana Maria Rosca
- Department of Dermatology, University Military Hospital “Dr. Carol Davila”, 010825 Bucharest, Romania;
| | - Mihai Lupu
- Department of Oncological Dermatology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.S.); (M.L.); (V.M.V.)
| | - Vlad Mihai Voiculescu
- Department of Oncological Dermatology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.S.); (M.L.); (V.M.V.)
- Department of Dermatology and Allergology, Elias University Emergency Hospital, 011461 Bucharest, Romania;
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Khan AM, Micho Ulbeh T, Zonder J, Balasubramanian S. Inflammation of actinic keratosis from chemotherapy in a relapsed multiple myeloma patient. BMJ Case Rep 2023; 16:e256024. [PMID: 37989327 PMCID: PMC10668170 DOI: 10.1136/bcr-2023-256024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2023] Open
Abstract
A man in his 60 s with a history of actinic keratosis (AK) and relapsed IgG kappa multiple myeloma (MM) recently received VD-PACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) chemotherapy and presented with numerous haemorrhagic, scaly lesions on his scalp and face. He also had sepsis from methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. Since the lesions were only present in the areas of pre-existing AK, a diagnosis of inflammation of AK secondary to chemotherapy was made. Sepsis was treated with appropriate antibiotics, and inflammation of AK was managed with topical steroids, leading to complete recovery.
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Affiliation(s)
- Abdul Moiz Khan
- Department of Hematology/Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA
| | - Tarec Micho Ulbeh
- Department of Internal medicine, Detroit Medical Center/Wayne State University, Detroit, Michigan, USA
| | - Jeffrey Zonder
- Department of Hematology/Oncology, Wayne State University, Detroit, Michigan, USA
| | - Suresh Balasubramanian
- Department of Hematology/Oncology, Wayne State University, Detroit, Michigan, USA
- Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland, Ohio, USA
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Kerche LE, Carrara IM, Marinello PC, Cavalcante DGSM, Danna CS, Cecchini R, Cecchini AL, Job AE. Antioxidant and photoprotective role of latex C-serum from Hevea brasiliensis during 15-week UVB irradiation in male hairless SKH-1 mice. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART A 2023; 86:846-858. [PMID: 37671816 DOI: 10.1080/15287394.2023.2255885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/07/2023]
Abstract
It is known that UVB radiation induces several adverse skin alterations starting from simple photoaging to skin cancer. In addition, it was demonstrated that reactive oxygen species (ROS) were found to be related to cancer development and progression. The aim of study was to examine whether male hairless (SKH-1) mice (Mus musculus) that were subchronically exposed to UVB radiation presented with actinic keratosis (AK) and squamous cell carcinoma lesions, and that treatment with latex C-serum cream significantly prevented abnormal skin development. Data demonstrated for the first time the photoprotective activity of latex C-serum extracted from the rubber tree Hevea brasiliensis var. subconcolor Ducke. Latex C-serum prevented the progression of AK to squamous cell carcinoma in SKH-1 mice, indicating that mice topically treated with latex C-serum presented only AK lesions and treatment with the highest concentration (10%) significantly reduced epidermal thickness, suggesting diminished cell proliferation. Latex C-serum protected the skin of mice against oxidative stress damage, increasing catalase (CAT) activity, regenerating glutathione (GSH) levels, lowering thiobarbituric acid-reactive species (TBARS) production and regenerating the total antioxidant capacity (TAC) of the skin. Evidence that UV radiation in skin induced systemic alterations and erythrocytic analysis indicated that latex C-serum increased CAT activity and GSH levels. Taken together these data indicate that latex C-serum plays an important antioxidant and photoprotective role, preventing serious damage to the skin following exposure to UVB radiation.
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Affiliation(s)
- Leandra E Kerche
- Department of Physics, Chemistry and Biology, São Paulo State University, Presidente Prudente, SP, Brazil
- Department of Physiological Sciences, Western São Paulo University, Presidente Prudente, SP, Brazil
| | - Iriana M Carrara
- Department of General Pathology, Londrina State University, Londrina, PR, Brazil
| | - Poliana C Marinello
- Department of General Pathology, Londrina State University, Londrina, PR, Brazil
| | - Dalita G S M Cavalcante
- Department of Physics, Chemistry and Biology, São Paulo State University, Presidente Prudente, SP, Brazil
| | - Caroline S Danna
- Department of Physics, Chemistry and Biology, São Paulo State University, Presidente Prudente, SP, Brazil
| | - Rubens Cecchini
- Department of General Pathology, Londrina State University, Londrina, PR, Brazil
| | | | - Aldo E Job
- Department of Physics, Chemistry and Biology, São Paulo State University, Presidente Prudente, SP, Brazil
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Azimi A, Jabbour S, Patrick E, Fernandez-Penas P. Non-invasive diagnosis of early cutaneous squamous cell carcinoma. Exp Dermatol 2023; 32:1946-1959. [PMID: 37688398 DOI: 10.1111/exd.14921] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 07/28/2023] [Accepted: 08/27/2023] [Indexed: 09/10/2023]
Abstract
Early cutaneous squamous cell carcinoma (cSCC) can be challenging to diagnose using clinical criteria as it could present similar to actinic keratosis (AK) or Bowen's disease (BD), precursors of cSCC. Currently, histopathological assessment of an invasive biopsy is the gold standard for diagnosis. A non-invasive diagnostic approach would reduce patient and health system burden. Therefore, this study used non-invasive sampling by tape-stripping coupled with data-independent acquisition mass spectrometry (DIA-MS) proteomics to profile the proteome of histopathologically diagnosed AK, BD and cSCC, as well as matched normal samples. Proteomic data were analysed to identify proteins and biological functions that are significantly different between lesions. Additionally, a support vector machine (SVM) machine learning algorithm was used to assess the usefulness of proteomic data for the early diagnosis of cSCC. A total of 696 proteins were identified across the samples studied. A machine learning model constructed using the proteomic data classified premalignant (AK + BD) and malignant (cSCC) lesions at 77.5% accuracy. Differential abundance analysis identified 144 and 21 protein groups that were significantly changed in the cSCC, and BD samples compared to the normal skin, respectively (adj. p < 0.05). Changes in pivotal carcinogenic pathways such as LXR/RXR activation, production of reactive oxygen species, and Hippo signalling were observed that may explain the progression of cSCC from premalignant lesions. In summary, this study demonstrates that DIA-MS analysis of tape-stripped samples can identify non-invasive protein biomarkers with the potential to be developed into a complementary diagnostic tool for early cSCC.
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Affiliation(s)
- Ali Azimi
- Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, New South Wales, Australia
- Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia
- Department of Dermatology, Westmead Hospital, Westmead, New South Wales, Australia
| | - Steven Jabbour
- Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, New South Wales, Australia
- Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia
- Department of Dermatology, Westmead Hospital, Westmead, New South Wales, Australia
| | - Ellis Patrick
- Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia
- School of Mathematics and Statistics, Faculty of Science, The University of Sydney, Camperdown, New South Wales, Australia
- Sydney Precision Data Science Centre, The University of Sydney, Camperdown, New South Wales, Australia
| | - Pablo Fernandez-Penas
- Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, New South Wales, Australia
- Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia
- Department of Dermatology, Westmead Hospital, Westmead, New South Wales, Australia
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Karampinis E, Aloizou AM, Zafiriou E, Bargiota A, Skaperda Z, Kouretas D, Roussaki-Schulze AV. Non-Melanoma Skin Cancer and Vitamin D: The "Lost Sunlight" Paradox and the Oxidative Stress Explanation. Antioxidants (Basel) 2023; 12:antiox12051107. [PMID: 37237973 DOI: 10.3390/antiox12051107] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/12/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023] Open
Abstract
UV radiation (UVR) is responsible for inducing both harmful and beneficial effects on skin health. Specifically, it has been reported to disrupt oxidant and antioxidant levels, leading to oxidative stress conditions in skin tissue. This phenomenon might trigger photo-carcinogenesis, resulting in melanoma, NMSC (non-melanoma skin cancer), such as BCC (basal cell carcinoma) and SCC (squamous cell carcinoma), and actinic keratosis. On the other hand, UVR is essential for the production of adequate vitamin D levels, a hormone with important antioxidant, anticancer and immunomodulatory properties. The exact mechanisms implicated in this two-fold action are not well understood, as there still no clear relation established between skin cancer and vitamin D status. Oxidative stress seems to be a neglected aspect of this complex relation, despite its role in both skin cancer development and vitamin D deficiency. Therefore, the aim of the present study is to examine the correlation between vitamin D and oxidative stress in skin cancer patients. A total of 100 subjects (25 with SCC, 26 with BCC, 23 with actinic keratosis, and 27 controls) were assessed in terms of 25-hydroxyvitamin D (25(OH) D) and redox markers such as thiobarbituric acid reactive substances (TBARS), protein carbonyls, total antioxidant capacity (TAC) in plasma, glutathione (GSH) levels and catalase activity in erythrocytes. The majority of our patients revealed low vitamin D levels; 37% of the subjects showed deficiency (<20 ng/mL) and 35% insufficiency (21-29 ng/mL). The mean 25(OH) D level of the NMSC patients (20.87 ng/mL) was also found to be significantly lower (p = 0.004) than that of the non-cancer patients (28.14 ng/mL). Furthermore, higher vitamin D levels were also correlated with lower oxidative stress (positive correlation with GSH, catalase activity TAC index and negative correlation with TBARS and CARBS indices). NMSC patients diagnosed with SCC showed lower catalase activity values compared to non-cancer patients (p < 0.001), with the lowest values occurring in patients with a chronic cancer diagnosis (p < 0.001) and vitamin D deficiency (p < 0.001). Higher GSH levels (p = 0.001) and lower TBARS levels (p = 0.016) were found in the control group compared to the NMSC group, and to patients with actinic keratosis. Higher levels of CARBS were observed in patients with SCC (p < 0.001). Non-cancer patients with vitamin D sufficiency showed higher TAC values compared to non-cancer patients with vitamin D deficiency (p = 0.023) and to NMSC patients (p = 0.036). The above-mentioned results indicate that NMSC patients reveal increased levels of oxidative damage markers compared to control levels, while vitamin D status plays a critical role in the determination of individuals' oxidative status.
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Affiliation(s)
- Emmanouil Karampinis
- Department of Dermatology, University General Hospital Larissa, University of Thessaly, 41500 Larissa, Greece
| | - Athina-Maria Aloizou
- Department of Neurology, St. Josef Klinikum Bochum, Ruhr Universität Bochum, 44892 Bochum, Germany
| | - Efterpi Zafiriou
- Department of Dermatology, University General Hospital Larissa, University of Thessaly, 41500 Larissa, Greece
| | - Alexandra Bargiota
- Department of Endocrinology, University General Hospital Larissa, University of Thessaly, 41500 Larissa, Greece
| | - Zoi Skaperda
- Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece
| | - Demetrios Kouretas
- Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece
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Reyes-Marcelino G, McLoughlin K, Harrison C, Watts CG, Kang YJ, Aranda S, Aitken JF, Guitera P, Cust AE. Skin cancer-related conditions managed in general practice in Australia, 2000-2016: a nationally representative, cross-sectional survey. BMJ Open 2023; 13:e067744. [PMID: 37142316 PMCID: PMC10186445 DOI: 10.1136/bmjopen-2022-067744] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 04/05/2023] [Indexed: 05/06/2023] Open
Abstract
OBJECTIVE Skin cancer is Australia's most common and costly cancer. We examined the frequency of Australian general practice consultations for skin cancer-related conditions, by patient and general practitioner (GP) characteristics and by time period. DESIGN Nationally representative, cross-sectional survey of general practice clinical activity. SETTING, PARTICIPANTS Patients aged 15 years or older having a skin cancer-related condition managed by GPs in the Bettering the Evaluation And Care of Health study between April 2000 and March 2016. PRIMARY OUTCOME MEASURES Proportions and rates per 1000 encounters. RESULTS In this period, 15 678 GPs recorded 1 370 826 patient encounters, of which skin cancer-related conditions were managed 65 411 times (rate of 47.72 per 1000 encounters, 95% CI 46.41 to 49.02). Across the whole period, 'skin conditions' managed were solar keratosis (29.87%), keratinocyte cancer (24.85%), other skin lesion (12.93%), nevi (10.98%), skin check (10.37%), benign skin neoplasm (8.76%) and melanoma (2.42%). Over time, management rates increased for keratinocyte cancers, skin checks, skin lesions, benign skin neoplasms and melanoma; but remained stable for solar keratoses and nevi. Skin cancer-related encounter rates were higher for patients aged 65-89 years, male, living in Queensland or in regional or remote areas, with lower area-based socioeconomic status, of English-speaking background, Veteran card holders and non-healthcare card holders; and for GPs who were aged 35-44 years or male. CONCLUSION These findings show the spectrum and burden of skin cancer-related conditions managed in general practice in Australia, which can guide GP education, policy and interventions to optimise skin cancer prevention and management.
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Affiliation(s)
- Gillian Reyes-Marcelino
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
| | - Kirstie McLoughlin
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia
| | - Christopher Harrison
- Menzies Centre for Health Policy and Economics, Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia
| | - Caroline G Watts
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
- Kirby Institute, UNSW, Sydney, NSW, Australia
| | - Yoon-Jung Kang
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia
| | - Sanchia Aranda
- Centre for Health Economics Research and Evaluation, University of Technology Sydney, Sydney, NSW, Australia
- Department of Nursing, The University of Melbourne, Melbourne, VIC, Australia
| | - Joanne F Aitken
- Cancer Council Queensland, Brisbane, QLD, Australia
- School of Public Health, The University of Queensland, Brisbane, QLD, Australia
| | - Pascale Guitera
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
- Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
- Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Anne E Cust
- The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia
- Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
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12
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Kim HN, Kim H, Gim JA, Baek YS, Kim A, Kim C. Factors for risk stratification of patients with actinic keratosis using integrated analysis of clinicopathological features and gene expression patterns. Australas J Dermatol 2023; 64:80-91. [PMID: 36645414 DOI: 10.1111/ajd.13965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 11/22/2022] [Accepted: 11/30/2022] [Indexed: 01/17/2023]
Abstract
BACKGROUND Actinic keratosis (AK) is considered as precursor lesion of invasive squamous cell carcinoma. Molecular studies on AK are limited because of too small size of the biopsy specimen to obtain enough DNA or RNA. METHODS Twenty biopsy cases of AK, followed by second same-sited biopsies, were included. Ten cases were diagnosed with total regression (regression group), while the other 10 were diagnosed with invasive carcinoma (progression group) in the follow-up biopsies. Using digital spatial profiling (DSP) technology, whole-gene expression analysis defined by specific regions of interest was performed for all 20 cases. After the clinicopathological features were assessed, separate and integrated analyses of these features and gene expression patterns were performed using machine-learning technology. All analyses were performed on both lesion keratinocytes (KT) and infiltrated stromal lymphocytes (LC). RESULTS Among the 18,667 genes assessed, 33 and 72 differentially expressed genes (DEGs) between the regression and progression groups were found in KT and LC respectively. The primary genes distinguishing the two groups were KRT10 for KT and CARD18 for LC. Clinicopathological features were weaker in risk stratification of AK progression than the gene expression patterns. Pathways associated with various cancers were upregulated in the progression group of KT, whereas the nucleotide-binding oligomerization domain (NOD)-like receptor signalling pathway was upregulated in the progression of LC. CONCLUSION Gene expression patterns were effective for risk stratification of AK progression, and their distinguishing power was higher than that of clinicopathological features.
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Affiliation(s)
- Han-Na Kim
- Department of Pathology, Korea University Guro Hospital, Seoul, South Korea
| | - Hayeon Kim
- Department of Pathology, Korea University Guro Hospital, Seoul, South Korea
| | - Jeong-An Gim
- Medical Science Research Center, College of Medicine, Korea University Guro Hospital, Seoul, South Korea
| | - Yoo S Baek
- Department of Dermatology, Korea University Guro Hospital, Seoul, South Korea
| | - Aeree Kim
- Department of Pathology, Korea University Guro Hospital, Seoul, South Korea
| | - Chungyeul Kim
- Department of Pathology, Korea University Guro Hospital, Seoul, South Korea
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13
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Pendlebury GA, Oro P, Ludlow K, Merideth D, Haynes W, Shrivastava V. Relevant Dermatoses Among U.S. Military Service Members: An Operational Review of Management Strategies and Telemedicine Utilization. Cureus 2023; 15:e33274. [PMID: 36741595 PMCID: PMC9891841 DOI: 10.7759/cureus.33274] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 12/26/2022] [Indexed: 01/04/2023] Open
Abstract
Despite skin being the largest and most exposed organ of the human body, skin issues can be challenging to diagnose in deployed military service members. Common reasons deployed soldiers seek dermatological evaluation include infections, inflammatory skin conditions, and skin growth. Due to limited access to specialized care in deployed settings, dermatological conditions are undertreated and underdiagnosed. As a result, dermatological conditions are a leading contributor to decreased combat effectiveness among deployed medical forces. To lessen the burden of dermatological diseases, military providers should promptly identify operational skin diseases and alleviate modifiable barriers faced by service members. In a post-pandemic era with novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and monkeypox infections, the duty to effectively treat operational skin lesions is ever important. The need for military dermatologists continues to rise as the global landscape continues to evolve with unprecedented infections and increased bioterrorism threats. Teledermatology offers many solutions to mitigate the high demand for dermatologists during pandemics. Dermatological consultations account for the highest number of telemedicine visits in the US Military Health System (MHS). As such, increased utilization of teledermatology will reduce infection-related dermatological sequelae and prevent the medical evacuation of service members from military operations. This review collates and categorizes relevant dermatological conditions encountered among deployed personnel. This report outlines the standard of care and modified treatments recommended according to potential barriers faced in operational settings.
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Affiliation(s)
- Gehan A Pendlebury
- Dermatology, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Davie, USA
| | - Peter Oro
- Internal Medicine, School of Osteopathic Medicine in Arizona, A.T. Still University, Mesa, USA
| | | | - Drew Merideth
- Emergency Medicine, School of Osteopathic Medicine in Arizona, A.T. Still University, Mesa, USA
| | - William Haynes
- Radiology, School of Osteopathic Medicine in Arizona, A.T. Still University, Mesa, USA
| | - Vikas Shrivastava
- Dermatology, Navy Medicine Readiness Training Command, Naval Medical Center San Diego, San Diego, USA
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14
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Schlesinger T, Stockfleth E, Grada A, Berman B. Tirbanibulin for Actinic Keratosis: Insights into the Mechanism of Action. Clin Cosmet Investig Dermatol 2022; 15:2495-2506. [PMID: 36415541 PMCID: PMC9675993 DOI: 10.2147/ccid.s374122] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 10/19/2022] [Indexed: 08/13/2023]
Abstract
Actinic keratosis (AK) is a common pre-neoplastic skin lesion constituted by uncontrolled proliferation of atypical keratinocytes that may evolve to squamous cell carcinoma. With global prevalence increasing, AK is expected to be the most common carcinoma of the skin. Tirbanibulin is a reversible tubulin polymerization inhibitor with potent anti-proliferative and anti-tumoral effects. In-vivo and in-vitro studies have shown that tirbanibulin significantly inhibits cell proliferation, tumor growth and downregulates Src signaling with no overt toxicity. Early phase and Phase III trials have shown high lesion clearance, compliance, and few side effects of once daily tirbanibulin treatment. This review discusses tirbanibulin anti-cancer activity, focusing on tubulin polymerization and Src signaling inhibitory effects, highlighting relevant literature and novel preclinical results from the ATNXUS-KX01-001 study. Furthermore, we address the relevant findings obtained in recent clinical trials to evaluate the safety, efficacy, pharmacokinetics, clearance efficacy, and side effects of the 1% tirbanibulin ointment applied once daily. In summary, we highlight preclinical and clinical evidence on the use of tirbanibulin as an effective and safe treatment option for AK.
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Affiliation(s)
| | - Eggert Stockfleth
- Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum, Bochum, Germany
| | - Ayman Grada
- Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Brian Berman
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
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15
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Actinic keratosis (review of literature). BIOMEDICAL PHOTONICS 2022. [DOI: 10.24931/2413-9432-2022-11-1-37-48] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Actinic keratosis is an important medical and social problem, the correct diagnosis and treatment of which will help to avoid the development of invasive forms of cutaneous squamous cell carcinoma. With the further development of the early diagnosis of cancer, including skin cancer, the increase in human life expectancy, and the popularization of travel to exotic countries, the number of cases of actinic keratosis among the population will continue to grow. In this regard, it is important to discuss the causes and pathogenesis of the disease, the varied clinical picture of the disease, methods of non-invasive diagnostics, as well as methods of treatment, of which there are a great many in the treatment of actinic keratosis today. However, each of the methods has both advantages and disadvantages, and in the global trend towards a personalized approach to treatment, it is important to choose from the standpoint of evidence-based medicine the most suitable for each individual patient. Moreover, after treatment of actinic keratosis, relapses often occur, which are the result of insufficient diagnosis and the development of incorrect treatment tactics. The review article provides the clinical picture of actinic keratosis, diagnostic and therapeutic methods, and their comparison with each other in terms of efficacy and safety
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16
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Climstein M, Doyle B, Stapelberg M, Rosic N, Hertess I, Furness J, Simas V, Walsh J. Point prevalence of non-melanoma and melanoma skin cancers in Australian surfers and swimmers in Southeast Queensland and Northern New South Wales. PeerJ 2022; 10:e13243. [PMID: 35505675 PMCID: PMC9057286 DOI: 10.7717/peerj.13243] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 03/18/2022] [Indexed: 01/13/2023] Open
Abstract
Background Surfing and swimming are two popular outdoor aquatic activities in Australia with an estimated 2.7 million surfers and three million swimmers; however, these activities are associated with intermittent exposure to ultraviolet radiation. Our aim was to determine the point prevalence of pre-skin cancer (actinic keratosis (PSC)), non-melanoma (NMSC) and melanoma skin cancers (MSC) in Australian surfers and swimmers. Methods This cross-sectional study involved Australian surfers who completed a survey that included physiological demographics, aquatic activity-specific demographics, history of skin cancer followed by screening. Results A total of 171 surfers (n = 116) and swimmers (n = 55) participated in the study. Both groups were identified as having a history of skin cancer (surfers 41.4%, swimmers 36.4%) and a family history of skin cancer (surfers 52.6%, swimmers 43.6%). The majority of both groups reported using a high percentage of a chemical or physical skin cancer prevention strategy (surfers 100%, Swimmers 92.7%, P = 0.003). Significantly more surfers were identified with a skin cancer of any type vs. swimmers (50% vs. 27.3%; OR 2.67; P = 0.005) with most the common skin cancer being PSC (44.7% vs. 11.3%, P = 0.076) followed by basal cell carcinoma (BCC) (24.2% vs. 7.6%, P = 0.068). There was a total of seven MSC identified in surfers and swimmers (4.6% vs. 0.8%, respectively, P = 0.137). Most skin cancers in surfers were located on the face (28.0%) followed by the arm and back (12.1% each), whereas in swimmers, the majority of skin cancers were identified on the face (17.3%), followed by the arm and lower leg (15.4% each). The highest number of melanomas were identified in surfers (n = 6) and mainly located on the face (n = 2) and back (n = 2). There was a single melanoma identified on the back in a swimmer. With the groups combined, the majority (42.9%) of melanomas were identified on the back in participants, followed by the face (28.6%). Rates per 100,000 of NMSC and MSC in surfers and swimmers (respectively) were BCC (11,206 vs. 14,545), squamous cell carcinoma (SCC) in situ (13,793 vs. 12,727), SCC (1,724 vs. 3,636) and MSC (5,172 vs. 1,818). When compared to the general Australian population, surfers and swimmers had higher odds ratios (OR), which included BCCs (OR 7.3 and 9.4, respectively), SCCs (OR 1.7 and 3.5, respectively) and MSC (OR 96.7 and 18.8, respectively). Conclusion Surfers and swimmers had consistently higher rates of PSC, NMSC and MSC than the general Australian population. Point prevalence of MSC (groups combined) was 76-fold higher than the general Australian population. These findings highlight the clinical importance of regular skin cancer screenings in individuals who surf or swim for early detection and treatment of skin cancer. Additionally, these aquatic enthusiasts should be advised of the benefits of sun protection strategies such as chemical and physical barriers to reduce the likelihood of developing skin cancer.
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Affiliation(s)
- Mike Climstein
- Aquatic Based Research/Faculty of Health, Southern Cross University, Bilinga, Queensland, Australia
- Exercise and Sport Science Exercise, Health & Performance Faculty Research Group Faculty of Health Sciences, University of Sydney, Sydney, NSW, Australia
- Water Based Research Unit, Bond University, Robina, Queensland, Australia
| | - Brendan Doyle
- Aquatic Based Research/Faculty of Health, Southern Cross University, Bilinga, Queensland, Australia
- John Flynn Specialist Centre, Advanced Skin Care, Tugan, Queensland, Australia
| | - Michael Stapelberg
- Aquatic Based Research/Faculty of Health, Southern Cross University, Bilinga, Queensland, Australia
- John Flynn Specialist Centre, Advanced Skin Care, Tugan, Queensland, Australia
| | - Nedeljka Rosic
- Biomedical Science/Faculty of Health, Southern Cross University, Bilinga, Queensland, Australia
| | - Isolde Hertess
- John Flynn Specialist Centre, Advanced Skin Care, Tugan, Queensland, Australia
| | - James Furness
- Water Based Research Unit, Bond University, Robina, Queensland, Australia
| | - Vini Simas
- Water Based Research Unit, Bond University, Robina, Queensland, Australia
| | - Joe Walsh
- Sports Science Institute, Sydney, NSW, Australia
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17
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Kim Y, Yin J, Huang H, Jorgenson E, Choquet H, Asgari MM. Genome-wide association study of actinic keratosis identifies new susceptibility loci implicated in pigmentation and immune regulation pathways. Commun Biol 2022; 5:386. [PMID: 35449187 PMCID: PMC9023580 DOI: 10.1038/s42003-022-03301-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 03/18/2022] [Indexed: 01/07/2023] Open
Abstract
Actinic keratosis (AK) is a common precancerous cutaneous neoplasm that arises on chronically sun-exposed skin. AK susceptibility has a moderate genetic component, and although a few susceptibility loci have been identified, including IRF4, TYR, and MC1R, additional loci have yet to be discovered. We conducted a genome-wide association study of AK in non-Hispanic white participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (n = 63,110, discovery cohort), with validation in the Mass-General Brigham (MGB) Biobank cohort (n = 29,130). We identified eleven loci (P < 5 × 10-8), including seven novel loci, of which four novel loci were validated. In a meta-analysis (GERA + MGB), one additional novel locus, TRPS1, was identified. Genes within the identified loci are implicated in pigmentation (SLC45A2, IRF4, BNC2, TYR, DEF8, RALY, HERC2, and TRPS1), immune regulation (FOXP1 and HLA-DQA1), and cell signaling and tissue remodeling (MMP24) pathways. Our findings provide novel insight into the genetics and pathogenesis of AK susceptibility.
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Affiliation(s)
- Yuhree Kim
- Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Jie Yin
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Hailiang Huang
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | | | - Hélène Choquet
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
| | - Maryam M Asgari
- Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA.
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
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18
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Topical Pharmacotherapy for Actinic Keratoses in Older Adults. Drugs Aging 2022; 39:143-152. [PMID: 35156172 PMCID: PMC8873057 DOI: 10.1007/s40266-022-00919-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2022] [Indexed: 11/21/2022]
Abstract
Actinic keratosis is caused by excessive lifetime sun exposure. It must be treated, regardless of thickness, because it is the biologic precursor of invasive squamous cell carcinoma, a potentially deadly malignancy. Physical ablative techniques such as cryotherapy, lasers, and curettage are the most used treatments for isolated lesions. Multiple lesions are treated with topical drugs, chemical peelings, and physical techniques. Drug preparations containing diclofenac plus hyaluronate, aminolevulinic acid, and methyl aminolevulinate and different concentrations of imiquimod and 5-fluorouracil are approved for this clinical indication. All treatments have a good profile of efficacy and tolerability although there are relevant differences in the clearance rate, tolerability, and type and frequency of adverse effects. In addition, they have very different mechanisms of action and treatment protocols. No differences in the efficacy and tolerability were found in older patients compared with younger patients, therefore no dose adjustments are needed. That said, older patients often need to be motivated to treat actinic keratoses and a careful attention to expectations, needs, and preferences should be used to obtain the maximal adherence and prevent treatment failure. This goal can be achieved with a careful evaluation not only of published efficacy, toxicity, and tolerability data but also of practical topics such as the frequency of daily applications, the overall duration of therapy, and the need for a caregiver. Finally, particular attention must be paid in the case of frail patients and immunosuppressed patients.
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19
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Molina-García M, Malvehy J, Granger C, Garre A, Trullàs C, Puig S. Exposome and Skin. Part 2. The Influential Role of the Exposome, Beyond UVR, in Actinic Keratosis, Bowen's Disease and Squamous Cell Carcinoma: A Proposal. Dermatol Ther (Heidelb) 2022; 12:361-380. [PMID: 35112326 PMCID: PMC8850498 DOI: 10.1007/s13555-021-00644-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Indexed: 02/07/2023] Open
Abstract
Actinic keratosis (AK) is the main risk factor for the development of cutaneous invasive squamous cell carcinoma (SCC). It represents the first sign of severe chronic ultraviolet radiation exposure, which has a clear significant effect. Nevertheless, the skin is exposed to many other exposome factors which should be thoroughly considered. Our aim was to assess the impact of exposome factors other than ultraviolet radiation (UVR) on the etiopathology of AK and Bowen's disease (BD) and progression of AK to SCC and to design tailored prevention strategies. We performed an exhaustive literature search in September 2021 through PubMed on the impact of exposome factors other than UVR on AK, BD and SCC. We conducted several parallel searches combining terms of the following topics: AK, BD, SCC and microbiome, hormones, nutrition, alcohol, tobacco, viral infections, chemical contaminants and air pollution. Notably, skin microbiome studies have shown how Staphylococcus aureus infections are associated with AK and AK-to-SCC progression by the production of chronic inflammation. Nutritional studies have demonstrated how a caloric restriction in fat intake, oral nicotinamide and moderate consumption of wine significantly reduce the number of premalignant keratoses and SCC. Regarding lifestyle factors, both alcohol and smoking are associated with the development of SCC in a dose-dependent manner. Relevant environmental factors are viral infections and chemical contaminants. Human papillomavirus infections induce deregulation of cellular proliferation and are associated with AK, BD and SCC. In addition to outdoor jobs, occupations such as industrial processing and farming also increase the risk of developing keratoses and SCC. The exposome of AK will undoubtedly help the understanding of its etiopathology and possible progression to SCC and will serve as a basis to design tailored prevention strategies.
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Affiliation(s)
- Manuel Molina-García
- School of Medicine and Health Science, University of Barcelona (UB), 143 Casanova, 08036 Barcelona, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Dermatology Department, Melanoma Unit, Hospital Clinic, Universitat de Barcelona, 170 Villarroel, 08036 Barcelona, Spain
| | - Josep Malvehy
- School of Medicine and Health Science, University of Barcelona (UB), 143 Casanova, 08036 Barcelona, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Dermatology Department, Melanoma Unit, Hospital Clinic, Universitat de Barcelona, 170 Villarroel, 08036 Barcelona, Spain
- Centro de Investigación en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
| | - Corinne Granger
- Innovation and Development, ISDIN, 33 Provençals, 08019 Barcelona, Spain
| | - Aurora Garre
- Innovation and Development, ISDIN, 33 Provençals, 08019 Barcelona, Spain
| | - Carles Trullàs
- Innovation and Development, ISDIN, 33 Provençals, 08019 Barcelona, Spain
| | - Susana Puig
- School of Medicine and Health Science, University of Barcelona (UB), 143 Casanova, 08036 Barcelona, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Dermatology Department, Melanoma Unit, Hospital Clinic, Universitat de Barcelona, 170 Villarroel, 08036 Barcelona, Spain
- Centro de Investigación en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
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20
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Zeerak S, Bhat Y, Rasool F, Akhtar S, Shah I, Yaseen A. Management of pre-malignant and malignant non-melanoma skin cancers: A study from a Tertiary Care Hospital of North India. J Cutan Aesthet Surg 2022; 15:118-123. [PMID: 35965913 PMCID: PMC9364464 DOI: 10.4103/jcas.jcas_241_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Introduction: The incidence of non-melanoma skin cancers (NMSCs) is increasing over the last few decades. This necessitates an early diagnosis which is nowadays aided by dermoscopy. Once diagnosed early, the treatment armamentarium is diverse and includes both topical and surgical modalities. Objective: Our aim was to diagnose pre-malignant and malignant NMSCs at an early stage and treat them as per the standard protocol. Materials and Materials: Out of 136 patients of pre-malignant and malignant tumors enrolled, 100 were taken up for treatment. These were then classified into various subtypes on the basis of clinical examination and dermoscopy. The selected patients were subjected to topical treatment or surgical modalities, wide local excision or flap excision, based on the type of tumor and its size. Results: The pre-malignant group included actinic keratoses, Bowen’s disease, and keratoacanthoma, whereas the malignant group included undifferentiated squamous cell carcinoma (SCC), differentiated SCC, pigmented basal cell carcinoma (BCC), nodulo-ulcerative BCC, and superficial BCC. Actinic keratoses, superficial BCCs, and five cases of keratoacanthoma were treated with topical therapies with a resolution of 90% in 86.8% cases. All the remaining cases (62 in number) were treated with conventional and flap surgery with 88% and 89.1% clearance rates, respectively, with complications in only 7 patients. Conclusion: A prompt identification of NMSCs can enable selection of the appropriate treatment modality for a specific lesion and thus reduce their associated morbidity and mortality.
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21
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Babino G, Caccavale S, Pinto D, Trink A, Giuliani G, Rinaldi F, Argenziano G. A Randomized Double-Blind Parallel-Group Study to Evaluate the Long-Term Effects of a Medical Device Containing 0.3% Octatrienoic Acid in the Treatment of Grade III Actinic Keratosis. Dermatol Ther (Heidelb) 2021; 11:1751-1762. [PMID: 34476756 PMCID: PMC8484398 DOI: 10.1007/s13555-021-00594-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 08/13/2021] [Indexed: 11/28/2022] Open
Abstract
INTRODUCTION Actinic keratosis (AK) consists of skin lesions with a milder degree of keratinocytic atypia. It can be also referred to as "field of cancerization," which can potentially evolve to cutaneous squamous cell carcinoma (SCC). Several therapeutic options are currently available, but not all are indicated on hyperkeratotic lesions. This study aimed to test the efficacy and tolerability of a medical device containing 2,4,6-octatrienoic acid and urea for the treatment of hyperkeratotic AK lesions. METHODS Seventy male and female subjects with grade III AK were enrolled in this randomized double-blind parallel-group study. The product was applied once daily for three consecutive months. The primary efficacy endpoint was the reduction in the mean number of AK lesions per subject from baseline (T0) to the end of the trial (T1) and 3 months after the end of the treatment period (T2). Therefore, clearance of target AK lesions at the end of the treatment period and local skin reaction score (LSR) versus baseline were evaluated. RESULTS There was a decrease of mean values from baseline to visit T2 in both treatment groups, but the decrease (versus baseline values) was more evident in the Kerà K2 group than in the placebo group (-42.78, SD 26.53, versus -6.20, SD 31.57), and the difference was statistically significant (p < 0.001). For 70 subjects (56.7%) in the Kerà K2 group and 3 (11.54%) in the placebo group, a significant (p < 0.005) partial clearance was evidenced. The product was well tolerated, and no serious adverse events were reported during the duration of the trial. Subject self-assessment of acceptability, local tolerability, and the cosmetic result was good at both T1 and T2 for both groups. CONCLUSIONS The medical device has demonstrated good efficacy in the reduction of visible AKs, encouraging its use.
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Affiliation(s)
- Graziella Babino
- Dermatology Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Stefano Caccavale
- Dermatology Unit, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Daniela Pinto
- Human Microbiome Advanced Project, HMAP, Milan, Italy
| | - Anna Trink
- Human Microbiome Advanced Project, HMAP, Milan, Italy
| | | | - Fabio Rinaldi
- Human Microbiome Advanced Project, HMAP, Milan, Italy.
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22
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Hammadi R, Kúsz N, Dávid CZ, Behány Z, Papp L, Kemény L, Hohmann J, Lakatos L, Vasas A. Ingol and Ingenol-Type Diterpenes from Euphorbia trigona Miller with Keratinocyte Inhibitory Activity. PLANTS 2021; 10:plants10061206. [PMID: 34198524 PMCID: PMC8231945 DOI: 10.3390/plants10061206] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/07/2021] [Accepted: 06/08/2021] [Indexed: 12/11/2022]
Abstract
Ingenol mebutate, isolated from Euphorbia peplus, is an ingenane-type diterpenoid, primarily used for the topical treatment of actinic keratosis, a premalignant skin condition. The aim of our work was to investigate other Euphorbia species to find structurally similar diterpenes that can be used as alternatives to ingenol mebutate. Pharmacological investigation of Euphorbia candelabrum, Euphorbia cotinifolia, Euphorbia ramipressa, and Euphorbia trigona revealed the potent keratinocyte (HPV-Ker cell line) inhibitory activity of these spurge species. From the methanolic extract of the aerial parts of Euphorbia trigona Miller, the most active species, five ingol (1–5) and four ingenane-type diterpenoids (6–9) were isolated by various chromatographic separation techniques, including open column chromatography, vacuum liquid chromatography, thin-layer chromatography, and high-performance liquid chromatography. The structures of the compounds were determined by NMR spectroscopic analysis and by comparison of the assignations with the literature data. The cytotoxic activity of the compounds against keratinocytes was tested in vitro by using ingenol mebutate as a positive control. Among the isolated compounds, two ingenane derivatives (6 and 7) exhibited remarkably stronger cytotoxic activity (IC50 values 0.39 μM and 0.32 μM, respectively) on keratinocytes than ingenol mebutate (IC50 value 0.84 μM). These compounds could serve as starting materials for further investigations to find alternatives to Picato® (with active substance ingenol mebutate), which was withdrawn from marketing authorization in the European Union.
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Affiliation(s)
- Reham Hammadi
- Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, 6720 Szeged, Hungary; (R.H.); (N.K.); (C.Z.D.); (J.H.)
| | - Norbert Kúsz
- Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, 6720 Szeged, Hungary; (R.H.); (N.K.); (C.Z.D.); (J.H.)
| | - Csilla Zsuzsanna Dávid
- Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, 6720 Szeged, Hungary; (R.H.); (N.K.); (C.Z.D.); (J.H.)
| | - Zoltán Behány
- Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, 6720 Szeged, Hungary; (Z.B.); (L.K.)
| | - László Papp
- Botanical Garden, Eötvös Loránd University, Illés u. 25, 1083 Budapest, Hungary;
| | - Lajos Kemény
- Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, 6720 Szeged, Hungary; (Z.B.); (L.K.)
| | - Judit Hohmann
- Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, 6720 Szeged, Hungary; (R.H.); (N.K.); (C.Z.D.); (J.H.)
- Interdisciplinary Centre of Natural Products, University of Szeged, Eötvös u. 6, 6720 Szeged, Hungary
| | - Lóránt Lakatos
- Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, 6720 Szeged, Hungary; (Z.B.); (L.K.)
- Photo- and Chronobiology Group Eötvös Loránd Research Network (ELKH), Institute of Plant Biology, Biological Research Center Szeged, Temesvári krt. 62, 6726 Szeged, Hungary
- Correspondence: (L.L.); (A.V.); Tel.: +36-62546451 (A.V.)
| | - Andrea Vasas
- Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, 6720 Szeged, Hungary; (R.H.); (N.K.); (C.Z.D.); (J.H.)
- Correspondence: (L.L.); (A.V.); Tel.: +36-62546451 (A.V.)
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Peigottu MF, Sotgiu G, Biondi G, Saderi L, Montesu MA, Satta R. Observational study on actinic keratosis risk factors in Sardinia, Italy. Ital J Dermatol Venerol 2021; 156:266-267. [PMID: 33960757 DOI: 10.23736/s2784-8671.20.06637-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Maria F Peigottu
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Giovanni Sotgiu
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Gabriele Biondi
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy -
| | - Laura Saderi
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Maria A Montesu
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Rosanna Satta
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
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Yang D, Lei S, Pan K, Chen T, Lin J, Ni G, Liu J, Zeng X, Chen Q, Dan H. Application of photodynamic therapy in immune-related diseases. Photodiagnosis Photodyn Ther 2021; 34:102318. [PMID: 33940209 DOI: 10.1016/j.pdpdt.2021.102318] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 04/09/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023]
Abstract
Photodynamic therapy (PDT) is a therapeutic modality that utilizes photodamage caused by photosensitizers and oxygen after exposure to a specific wavelength of light. Owing to its low toxicity, high selectivity, and minimally invasive properties, PDT has been widely applied to treat various malignant tumors, premalignant lesions, and infectious diseases. Moreover, there is growing evidence of its immunomodulatory effects and potential for the treatment of immune-related diseases. This review mainly focuses on the effect of PDT on immunity and its application in immune-related diseases.
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Affiliation(s)
- Dan Yang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Shangxue Lei
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Keran Pan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Ting Chen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Jiao Lin
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Guangcheng Ni
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Jiaxin Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Xin Zeng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Qianming Chen
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China
| | - Hongxia Dan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renminnan Road, Chengdu, Sichuan 610041, China.
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25
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de Andrade FAG, Isoldi FC, Ferreira LM. Skin field cancerisation: A systematic review of the literature regarding its treatment. Eur J Cancer Care (Engl) 2020; 30:e13366. [PMID: 33174657 DOI: 10.1111/ecc.13366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 07/25/2020] [Accepted: 10/14/2020] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Skin neoplasms are the most frequent malignant lesions, increasing patient's morbidity when associated with skin field cancerisation. There is a need to understand the current therapies, both clinical and surgical. METHODS A systematic review was performed according to the PRISMA guideline, registered in PROSPERO: CRD42018114826, including studies from 2012 to 2019. RESULTS Seven hundred and eighty-two studies were found, of which 21 were included. Of these, 8 primary studies were randomised controlled trials: fractional CO2 laser-assisted photodynamic therapy (PDT) vs. PDT (no significance), daylight PDT vs. PDT (no significance, daylight PDT had less adverse effects), trichloroacetic acid peel vs. 5-aminolaevulinic acid PDT (clinical improvement of aminolaevulinic acid PDT), 5-Fluorouracil 0.5%/Salicylic Acid 10% vs. vehicle (clinical improvement of 5-Fluorouracil 0.5%/Salicylic Acid 10%), photolyase vs. sun filters (no significance), sunscreens vs. sunscreens plus DNA repair enzymes (DNA Repair Enzymes was more effective in reducing field cancerisation). Only one systematic review was included in which there was effectiveness of daylight PDT in the treatment of actinic keratoses. The other 12 included studies had a lower level of evidence including surgical studies. CONCLUSION Clinical studies are more relevant in the treatment of the field cancerisation. There is a lack of surgical studies.
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Affiliation(s)
- Fernando Antônio G de Andrade
- Plastic Surgery Service of Universidade Federal de Alagoas (UFAL), Discipline of Plastic Surgery of the Faculty of Medicine of UFAL, Maceió, Brazil
| | - Felipe C Isoldi
- Universidade Federal de São Paulo - Unifesp, Plastic Surgery Division, São Paulo, Brazil
| | - Lydia M Ferreira
- Universidade Federal de São Paulo - Unifesp, Plastic Surgery Division, São Paulo, Brazil
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26
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Sinclair R, Baker C, Spelman L, Supranowicz M, MacMahon B. A review of actinic keratosis, skin field cancerisation and the efficacy of topical therapies. Australas J Dermatol 2020; 62:119-123. [PMID: 32840870 PMCID: PMC8247342 DOI: 10.1111/ajd.13447] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 07/16/2020] [Accepted: 07/26/2020] [Indexed: 12/14/2022]
Abstract
While a wide range of treatments exist for actinic keratosis and skin field cancerisation, the long‐term benefits of the most common topical therapies are poorly defined. This report reviews the efficacy of the most commonly used topical therapies to treat regional or field lesions. Limited clinical and histopathological data are available on clearance rates at 12 months post‐treatment for the most commonly used agents, with varied outcome measures making any comparison difficult. In general, total field clearance rates at 12 months are suboptimal for the most commonly employed agents. Given the increasing incidence of actinic keratosis and skin field cancerisation due to an ageing population, further research into the efficacy of therapies is critical to guide treatment choice.
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Affiliation(s)
- Robert Sinclair
- Specialist Connect Services, Brisbane, Queensland, Australia
| | | | - Lynda Spelman
- Specialist Connect Services, Brisbane, Queensland, Australia
| | | | - Beth MacMahon
- Specialist Connect Services, Brisbane, Queensland, Australia
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27
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Moore AY, Nguyen M, Moore S. Cyclic calcipotriene 0.005% foam and 1% 5-fluorouracil cream after cryotherapy in treatment of hyperkeratotic actinic keratosis: A retrospective study. J Am Acad Dermatol 2020; 84:1148-1150. [PMID: 32652187 DOI: 10.1016/j.jaad.2020.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 06/26/2020] [Accepted: 07/01/2020] [Indexed: 10/23/2022]
Affiliation(s)
- Angela Yen Moore
- Arlington Research Center, Arlington, Texas; Baylor University Medical Center, Dallas, Texas; Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, Texas.
| | - Madalyn Nguyen
- Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, Texas
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28
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Segura S, Gadea A, Nonell L, Andrades E, Sánchez S, Pujol R, Hernández-Muñoz I, Toll A. Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel. PLoS One 2020; 15:e0232146. [PMID: 32413042 PMCID: PMC7228095 DOI: 10.1371/journal.pone.0232146] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 04/07/2020] [Indexed: 12/22/2022] Open
Abstract
Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma if left untreated. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood. In this study, we evaluated the gene expression profiles of actinic keratosis lesions before and after treatment with ingenol mebutate using microarray technology. Actinic keratoses on face/scalp of 15 immunocompetent patients were identified and evaluated after treatment with topical ingenol mebutate gel 0.015%, applied once daily for 3 consecutive days. Diagnostic and clearance of lesions was determined by clinical, dermoscopic, and reflectance confocal microscopy criteria. Lesional and non-lesional skin biopsies were subjected to gene expression analysis profiled by Affymetrix microarray. Differentially expressed genes were identified, and enrichment analyses were performed using STRING database. At 8 weeks post-treatment, 60% of patients responded to ingenol mebutate therapy, achieving complete clearance in 40% of cases. A total of 128 differentially expressed genes were identified following treatment, and downregulated genes (114 of 128) revealed changes in pathways important to epidermal development, keratinocyte differentiation and cornification. In responder patients, 388 downregulated genes (of 450 differentially expressed genes) were also involved in development/differentiation of the epidermis, and immune system-related pathways, such as cytokine and interleukin signaling. Cluster analysis revealed two relevant clusters showing upregulated profile patterns in pre-treatment actinic keratoses of responders, as compared to non-responders. Again, differentially expressed genes were mainly associated with cornification, keratinization and keratinocyte differentiation. Overall, the present study provides insight into the gene expression profile of actinic keratoses after treatment with ingenol mebutate, as well as identification of genetic signatures that could predict treatment response.
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Affiliation(s)
- Sonia Segura
- Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - Alejandra Gadea
- Group of Inflamatory and Neoplasic Dermatological Diseases, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
- Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Paul Pascal (CRPP), Université de Bordeaux, Pessac, France
| | - Lara Nonell
- MARGenomics, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - Evelyn Andrades
- Group of Inflamatory and Neoplasic Dermatological Diseases, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - Silvia Sánchez
- Group of Inflamatory and Neoplasic Dermatological Diseases, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - Ramon Pujol
- Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - Inmaculada Hernández-Muñoz
- Group of Inflamatory and Neoplasic Dermatological Diseases, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - Agustí Toll
- Department of Dermatology, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
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29
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Guorgis G, Anderson CD, Lyth J, Falk M. Actinic Keratosis Diagnosis and Increased Risk of Developing Skin Cancer: A 10-year Cohort Study of 17,651 Patients in Sweden. Acta Derm Venereol 2020; 100:adv00128. [PMID: 32314794 PMCID: PMC9128984 DOI: 10.2340/00015555-3486] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2020] [Indexed: 11/16/2022] Open
Abstract
Actinic keratosis is the most common actinic lesion in fair-skinned populations. It is accepted as an indicator of actinic skin damage and as an occasional precursor of squamous cell carcinoma. The aim of this study was to investigate, in a cohort of patients with a diagnosis of actinic keratosis, the relative risk of developing skin cancer during a follow-up period of 10 years. This registry-based cohort study compared a cohort of 2,893 individuals in south-eastern Sweden, who were diagnosed with actinic keratosis during the period 2000 to 2004, with a matched-control cohort of 14,668 individuals without actinic keratosis during the same inclusion period. The subjects were followed for 10 years to identify skin cancer development in both cohorts. Hazard ratios with 95% confidence intervals (95% CI) were used as risk measures. Individuals in the actinic keratosis cohort had a markedly higher risk for all skin cancer forms compared with the control cohort (hazard ratio (HR) 5.1, 95% CI 4.7-5.6). The relative risk was highest for developing squamous cell carcinoma (SCC) (HR 7.7, 95% CI 6.7-8.8) and somewhat lower for basal cell carcinoma (BCC) (HR 4.4, 95% CI 4.1-5.0) and malignant melanoma (MM) (HR 2.7 (2.1-3.6). Patients with a diagnosis of actinic keratosis were found to be at increased risk of developing SCC, BCC and MM in the 10 years following diagnosis of actinic keratosis. In conclusion, a diagnosis of actinic keratosis, even in the absence of documentation of other features of chronic sun exposure, is a marker of increased risk of skin cancer, which should be addressed with individually directed preventive advice.
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Affiliation(s)
- Ghassan Guorgis
- Department of Health, Medicine and Caring Sciences, Linköping University, SE-581 83 Linköping, Sweden
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30
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Bigge B, Ungerechts G, Bigge S. Photodynamic therapy and laser‐assisted drug delivery and
R0
excision in the treatment of an immunosuppressed patient showing multiple actinic keratosis and recurrent squamous cell carcinoma: A case report. TRANSLATIONAL BIOPHOTONICS 2020. [DOI: 10.1002/tbio.201900037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
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The Role of Nicotinamide in Cancer Chemoprevention and Therapy. Biomolecules 2020; 10:biom10030477. [PMID: 32245130 PMCID: PMC7175378 DOI: 10.3390/biom10030477] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 03/09/2020] [Accepted: 03/17/2020] [Indexed: 12/24/2022] Open
Abstract
Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and a precursor of nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production of adenosine triphosphate (ATP), NAD+ acts as a substrate for several enzymes including sirtuin 1 (SIRT1) and poly ADP-ribose polymerase 1 (PARP1). Notably, NAM is an inhibitor of both SIRT1 and PARP1. Accumulating evidence suggests that NAM plays a role in cancer prevention and therapy. Phase III clinical trials have confirmed its clinical efficacy for non-melanoma skin cancer chemoprevention or as an adjunct to radiotherapy against head and neck, laryngeal, and urinary bladder cancers. Evidence for other cancers has mostly been collected through preclinical research and, in its majority, is not yet evidence-based. NAM has potential as a safe, well-tolerated, and cost-effective agent to be used in cancer chemoprevention and therapy. However, more preclinical studies and clinical trials are needed to fully unravel its value.
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Răducu L, Avino A, Purnichescu Purtan R, Balcangiu-Stroescu AE, Bălan DG, Timofte D, Ionescu D, Jecan CR. Quality of Life in Patients with Surgically Removed Skin Tumors. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:E66. [PMID: 32050413 PMCID: PMC7074335 DOI: 10.3390/medicina56020066] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 01/31/2020] [Accepted: 02/02/2020] [Indexed: 12/11/2022]
Abstract
Background and Objectives: Skin cancer is one of the most frequently diagnosed malignancies. The main goal of the therapeutic management is total excision with the prevention of recurrence and metastasis. The quality of life of the patients with skin cancer is affected by the morbidity risk, surgery, and cosmetic or functional aspects. The aim of this study was to evaluate the quality of life of patients with skin cancer prior to and post surgical intervention. Material and methods: We performed a prospective study on 247 patients with skin tumors. Quality of life was evaluated through an initial questionnaire that was given to all consenting patients. This was used to determine patients' mobility, selfcare, normal activities, pain, and despair, using a five-point Likert scale. The general autoperceived health state was also recorded using a 100-point scale. The study included the responses of all patients at hospital admission, after one month of surgery, and after one year of surgery. Results: In patients with squamous cell carcinoma (SCC), the general health state indicator statistically significantly decreased one month after surgery and increased at one-year follow-up. In malignant melanoma (MM) patients, mobility, selfcare, normal activities, and discomfort presented a decrease in values one year after surgery, compared to the values registered at hospital admission. In patients with basal cell carcinoma (BCC), all indicators of quality of life presented an impaired value one year after surgery, after a decreasing trend. The general health state indicator statistically significantly increased one month after surgery and after one year. Conclusions: Surgery is one of the main steps in treating skin cancer. It has a great impact on patients' quality of life because of pain andthe effect on mobility and normal activities. Skin cancers influence the quality of life of patients both psychologicallyand physically.
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Affiliation(s)
- Laura Răducu
- Department of Plastic and Reconstructive Surgery, Clinical Emergency Hospital “Prof. Dr. Agrippa Ionescu”, 011356 Bucharest, Romania; (L.R.); (C.-R.J.)
- Department of Plastic and Reconstructive Surgery, Faculty of Medicine “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Adelaida Avino
- Department of Plastic and Reconstructive Surgery, Clinical Emergency Hospital “Prof. Dr. Agrippa Ionescu”, 011356 Bucharest, Romania; (L.R.); (C.-R.J.)
| | - Raluca Purnichescu Purtan
- Department of Mathematical Methods and Models, Faculty of Applied Sciences, University Politehnica of Bucharest, 060042 Bucharest, Romania;
| | - Andra-Elena Balcangiu-Stroescu
- Department of Dialysis, Emergency University Hospital Bucharest, 050098 Bucharest, Romania; (A.-E.B.-S.); (D.T.)
- Discipline of Physiology, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, 020021 Bucharest, Romania;
| | - Daniela Gabriela Bălan
- Discipline of Physiology, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, 020021 Bucharest, Romania;
| | - Delia Timofte
- Department of Dialysis, Emergency University Hospital Bucharest, 050098 Bucharest, Romania; (A.-E.B.-S.); (D.T.)
| | - Dorin Ionescu
- Discipline of Internal Medicine I and Nephrology, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
- Department of Nephrology, Emergency University Hospital Bucharest, 050098 Bucharest, Romania
| | - Cristian-Radu Jecan
- Department of Plastic and Reconstructive Surgery, Clinical Emergency Hospital “Prof. Dr. Agrippa Ionescu”, 011356 Bucharest, Romania; (L.R.); (C.-R.J.)
- Department of Plastic and Reconstructive Surgery, Faculty of Medicine “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
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Gollnick H, Dirschka T, Ostendorf R, Kerl H, Kunstfeld R. Long-term clinical outcomes of imiquimod 5% cream vs. diclofenac 3% gel for actinic keratosis on the face or scalp: a pooled analysis of two randomized controlled trials. J Eur Acad Dermatol Venereol 2020; 34:82-89. [PMID: 31407414 DOI: 10.1111/jdv.15868] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 07/08/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND Actinic keratosis (AK) is an early in situ epidermal cancer which can progress to invasive squamous cell carcinoma (SCC). Imiquimod 5% cream (IMIQ) and diclofenac 3% gel (DIC) are frequently used to treat AK; however, their long-term effects following repeated treatment cycles have never been compared. OBJECTIVE To compare IMIQ and DIC in the treatment of AK with respect to the risk of change to grade III AK or invasive SCC, after 3 years. METHODS Data were pooled from two randomized, active-controlled, open-label, multicentre, multinational, phase IV studies (Clinicaltrials.gov NCT00777127/NCT01453179), with two parallel groups. Studies were conducted between 2008 and 2015 and were almost identical in design. Patients eligible for inclusion were immunocompetent adults with 5-10 visible AK lesions on the face/scalp and grade I/II AK. The primary endpoint was inhibition of histological change to grade III AK or invasive SCC in the study treatment area, observed until month 36. Patients applied either IMIQ or DIC for a maximum of six treatment cycles. RESULTS In total, 479 patients (IMIQ 242; DIC 237) were included in the full analysis set. Histological change to grade III AK or invasive SCC was observed until month 36 in 13 (5.4%) patients treated with IMIQ, compared with 26 (11.0%) patients treated with DIC (absolute risk difference -5.6% [95% confidence interval -10.7%, -0.7%]). Time to histological change was greater in the IMIQ group than the DIC group (P = 0.0266). Frequency of progression to invasive SCC was lower with IMIQ than with DIC at all time points. Initial clearance rate was higher in the IMIQ group compared with the DIC group, while recurrence rate was lower. Both treatments were well tolerated. CONCLUSIONS Over 3 years, IMIQ was superior to DIC in clearing AK lesions and preventing histological change to grade III AK or invasive SCC and recurrence.
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Affiliation(s)
- H Gollnick
- Department of Dermatology and Venereology, Otto-von-Guericke University, Magdeburg, Germany
| | - T Dirschka
- Centroderm Clinic, Wuppertal, Germany
- Faculty of Health, University of Witten-Herdecke, Witten, Germany
| | | | - H Kerl
- Department of Dermatology, Medical University of Graz, Graz, Austria
| | - R Kunstfeld
- Dermatology Clinic, General Hospital, Vienna, Austria
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Carcinomes épidermoïdes multiples après traitement par ingénol mébutate. Ann Dermatol Venereol 2019; 146:823-825. [DOI: 10.1016/j.annder.2019.08.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 01/18/2019] [Accepted: 08/19/2019] [Indexed: 01/10/2023]
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Reinehr CPH, Bakos RM. Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. An Bras Dermatol 2019; 94:637-657. [PMID: 31789244 PMCID: PMC6939186 DOI: 10.1016/j.abd.2019.10.004] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Accepted: 10/17/2019] [Indexed: 02/07/2023] Open
Abstract
Actinic keratoses are dysplastic proliferations of keratinocytes with potential for malignant transformation. Clinically, actinic keratoses present as macules, papules, or hyperkeratotic plaques with an erythematous background that occur on photoexposed areas. At initial stages, they may be better identified by palpation rather than by visual inspection. They may also be pigmented and show variable degrees of infiltration; when multiple they then constitute the so-called field cancerization. Their prevalence ranges from 11% to 60% in Caucasian individuals above 40 years. Ultraviolet radiation is the main factor involved in pathogenesis, but individual factors also play a role in the predisposing to lesions appearance. Diagnosis of lesions is based on clinical and dermoscopic examination, but in some situations histopathological analysis may be necessary. The risk of transformation into squamous cell carcinoma is the major concern regarding actinic keratoses. Therapeutic modalities for actinic keratoses include topical medications, and ablative and surgical methods; the best treatment option should always be individualized according to the patient.
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Affiliation(s)
| | - Renato Marchiori Bakos
- Department of Dermatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
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Fu C, Kuang BH, Qin L, Zeng XY, Wang BC. Efficacy and safety of photodynamic therapy with amino-5-laevulinate nanoemulsion versus methyl-5-aminolaevulinate for actinic keratosis: A meta-analysis. Photodiagnosis Photodyn Ther 2019; 27:408-414. [PMID: 31310826 DOI: 10.1016/j.pdpdt.2019.07.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Revised: 07/08/2019] [Accepted: 07/12/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Photodynamic therapy is an effective treatment for actinic keratosis. 5-aminolevulinic acid nanoemulsion (BF-200 ALA) and methyl-5-aminolevulinate (MAL) are both prodrugs for the treatment of actinic keratosis with photodynamic therapy. A comparison of the efficacy and safety between the drugs is critical for clinical practice. OBJECTIVES To investigate if photodynamic therapy in combination with BF-200 ALA is superior to photodynamic therapy with MAL for actinic keratosis. METHODS We performed a meta-analysis to investigate the combination of photodynamic therapy with BF-200 ALA and with MAL. The PubMed, Cochrane Library, Web of Science and EMBASE databases were searched to select eligible randomized controlled trials. Our search was conducted on April 1, 2019, and included the search terms "5-aminolevulinic acid nanoemulsion or BF-200 ALA", "methyl-5-aminolevulinate or methyl aminolaevulinate" and "actnic keratosis". Cochrane Risk of Bias Tool was used to estimate the risk of bias. RESULTS The meta-analysis consisted of 5988 actinic keratosis lesions in five eligible randomized controlled trials, with a total of 2953 actinic keratosis lesions treated with BF-200 ALA and 3035 actinic keratosis lesions treated with MAL. BF-200 ALA in combination with photodynamic therapy showed significantly higher overall complete clearance rates (RR: 1.07, 95% CI 1.02-1.12, p = 0.01) and 3 month complete clearance rates (RR: 1.09, 95% CI 1.06-1.12, p < 0.00001) compared to MAL. A subgroup analysis was performed for photodynamic therapy combined with BF-200 ALA, revealing increased complete clearance rates of grade II-III lesions in comparison with MAL (RR: 1.24, 95% CI 1.05-1.46, p = 0.01). Compared with MAL, the pooled relative risk for the meta-analysis for recurrence was 0.67 (95% CI 0.48-0.92, p = 0.01) at 12 month after BF-200 ALA treatment. CONCLUSION Photodynamic therapy with BF-200 ALA has a 9% better chance of complete clearance at 3 months and a 24% better chance of grade II-III lesions after treatment than with MAL for patients with actinic keratosis.
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Affiliation(s)
- Chen Fu
- Department of Dermatology, the First Hospital of Wuhan, Wuhan 430022, China
| | - Bo-Hua Kuang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Li Qin
- Department of Dermatology, the First Hospital of Wuhan, Wuhan 430022, China
| | - Xian-Yu Zeng
- Department of Dermatology, the First Hospital of Wuhan, Wuhan 430022, China
| | - Bi-Cheng Wang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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Verteporfin-loaded mesoporous silica nanoparticles inhibit mouse melanoma proliferation in vitro and in vivo. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2019; 197:111533. [PMID: 31254952 DOI: 10.1016/j.jphotobiol.2019.111533] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 06/07/2019] [Accepted: 06/12/2019] [Indexed: 12/22/2022]
Abstract
Melanoma is one of the most lethal tumors among the skin cancers, arising from complex genetic mutations in melanocyte. Melanoma microenvironment is very heterogeneous, showing complex vascular networks and immunogenicity, as well as induced acquired resistance to treatments by upregulation of multidrug resistance (MDR) mechanisms. Different studies have showed that Photodynamic Therapy (PDT) could be considered a new potential approach for melanoma treatment. PDT combines a light with a specific wavelength and a photosensitizer: when these two elements interact reactive oxygen species (ROS) are generated leading to tumor cell destruction. In this study verteporfin (Ver), a second-generation photosensitizer, has been conjugated with mesoporous silica nanoparticles (MSNs): the resulting Ver-MSNs are an efficient nanoplatforms used to enhance cargo capacity and cellular uptake. Our in vitro and in vivo studies investigated whether Ver-MSNs were able to reduce or inhibit melanoma growth. In vitro experiments performed using B16F10 mouse melanoma cells showed that Ver-MSNs stimulated by red light (693 nm) significantly decreased in vitro cells proliferation in a range of concentration between 0.1 μg/ml to 10 μg/ml. When Ver-MSNs (5 μg/ml in glycerol) were topically administrated to melanoma tumor mass developed in mice and stimulated by red light for four times in 16 days, they were able to reduce the tumor mass of 50.2 ± 6,6% compared to the untreated (only glycerol) mice. In the light of this information, PDT performed using Ver-MSNs could be considered a new promising and potential approach to treat melanoma.
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Khadra I, Obeid MA, Dunn C, Watts S, Halbert G, Ford S, Mullen A. Characterisation and optimisation of diclofenac sodium orodispersible thin film formulation. Int J Pharm 2019; 561:43-46. [PMID: 30772459 DOI: 10.1016/j.ijpharm.2019.01.064] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 01/11/2019] [Accepted: 01/28/2019] [Indexed: 11/23/2022]
Abstract
Oral Thin Film (OTF) is a newly emerging drug delivery system which has many benefits for patients. Although there has been some formulation of OTF products, these have mainly been as confectionary or dental health products. The most significant benefit of this dosage format will only be realised once more pharmaceutical products become available. Within this paper, OTF strips containing Diclofenac Sodium were prepared using the solvent casting method and then characterised to ensure the method could conform to acceptable levels of uniformity, the mean (SD) diclofenac sodium content was 25.43 (1.39) mg, range 22.84-27.44 mg. Bioburden was tested against coliforms, yeasts and moulds and all results were confirmed to be <10 CFU/g, also similar dissolution profile when compared to a commercial product to ensure biowaiver. An acceptable level of uniformity of mass was produced. K-F titration was employed to reduce the water content of the strips and it was found to be acceptable, this represented a level of water which would not be viable for microbial growth. The technique employed here in the production of OTF resulted in high quality products and amenability to being up scaled. Furthermore, the characterisation method was also sufficient to assess the quality of the products and may be used for future analysis of OTF pharmaceuticals.
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Affiliation(s)
- Ibrahim Khadra
- Department of Pharmaceutical Sciences, Institute of Pharmacy and Biomedical Sciences, University Of Strathclyde, Glasgow, UK.
| | | | - Claire Dunn
- Department of Pharmaceutical Sciences, Institute of Pharmacy and Biomedical Sciences, University Of Strathclyde, Glasgow, UK
| | - Stewart Watts
- Department of Pharmaceutical Sciences, Institute of Pharmacy and Biomedical Sciences, University Of Strathclyde, Glasgow, UK
| | - Gavin Halbert
- Cancer Research-UK, Institute of Pharmacy and Biomedical Sciences, University Of Strathclyde, Glasgow, UK
| | - Steve Ford
- Department of Pharmaceutical Sciences, Institute of Pharmacy and Biomedical Sciences, University Of Strathclyde, Glasgow, UK
| | - Alexander Mullen
- Department of Pharmaceutical Sciences, Institute of Pharmacy and Biomedical Sciences, University Of Strathclyde, Glasgow, UK
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Carrara IM, Melo GP, Bernardes SS, Neto FS, Ramalho LNZ, Marinello PC, Luiz RC, Cecchini R, Cecchini AL. Looking beyond the skin: Cutaneous and systemic oxidative stress in UVB-induced squamous cell carcinoma in hairless mice. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2019; 195:17-26. [PMID: 31035030 DOI: 10.1016/j.jphotobiol.2019.04.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 04/12/2019] [Accepted: 04/15/2019] [Indexed: 12/25/2022]
Abstract
Cumulative ultraviolet (UV) exposure is associated with squamous skin cell carcinoma. UV radiation induces oxidative modifications in biomolecules of the skin leading to photocarcinogenesis. Indeed, the cyclobutene pyrimidine dimers and other dimers formed by photoaddition between carbon-carbon bonds also have an important role in the initiation process. However, information on the systemic redox status during these processes is scarce. Thus, we investigated the systemic redox profile in UVB-induced squamous cell carcinoma in mice. Female hairless mice were exposed to UVB radiation (cumulative dose = 17.1 J/cm2). The dorsal skin of these mice developed actinic keratosis (AK) and squamous cell carcinoma (SCC) and presented increased levels of oxidative and nitrosative stress biomarkers (4-hydroxy-2-nonenal and 3-nitrotyrosine), and decreased antioxidant defenses. Systemically, we observed the consumption of plasmatic antioxidant defenses and increased levels of advanced oxidized protein products (AOPP), an oxidative stress product derived from systemic inflammatory response. Taken together, our results indicate that UVB chronic irradiation leads not only to adjacent and tumoral oxidative stress in the skin, but it systemically is reflected through the blood. These new findings clarify some aspects of the pathogenesis of SCC and should assist in formulating better chemoprevention strategies, while avoiding additional primary SCC development and metastasis.
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Affiliation(s)
- Iriana Moratto Carrara
- Laboratory of Molecular Pathology, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil; Laboratory of Pathophysiology and Free Radicals, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil
| | - Gabriella Pasqual Melo
- Laboratory of Molecular Pathology, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil; Laboratory of Pathophysiology and Free Radicals, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil
| | - Sara Santos Bernardes
- Laboratory of Molecular Pathology, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil; Laboratory of Healthy Sciences Research, Federal University of Grande Dourados (UFGD), Dourados, Mato Grosso do Sul, Brazil, UFGD, R. João Rosa Góes, 1761 - Vila Progresso, Dourados, MS, 79825-070, Brazil.
| | - Fernando Souza Neto
- Laboratory of Molecular Pathology, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil; Laboratory of Pathophysiology and Free Radicals, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil
| | - Leandra Naira Zambelli Ramalho
- Department of Pathology, Ribeirão Preto Medical School (FMRP), University of São Paulo (USP), FMRP, Av. Bandeirantes, 3900 - Monte Alegre, Ribeirão Preto, SP, 14049-900, Brazil.
| | - Poliana Camila Marinello
- Laboratory of Molecular Pathology, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil
| | - Rodrigo Cabral Luiz
- Laboratory of Molecular Pathology, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil
| | - Rubens Cecchini
- Laboratory of Pathophysiology and Free Radicals, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil
| | - Alessandra Lourenço Cecchini
- Laboratory of Molecular Pathology, Londrina State University (UEL), Londrina, Paraná, Brazil, UEL, Rod. Celso Garcia Cid, PR-445, km 380, 86051-990 Londrina, Paraná, Brazil.
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Thomas GJ, Herranz P, Cruz SB, Parodi A. Treatment of actinic keratosis through inhibition of cyclooxygenase-2: Potential mechanism of action of diclofenac sodium 3% in hyaluronic acid 2.5. Dermatol Ther 2019; 32:e12800. [PMID: 30523664 PMCID: PMC6767532 DOI: 10.1111/dth.12800] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Revised: 11/29/2018] [Accepted: 12/03/2018] [Indexed: 01/08/2023]
Abstract
Cyclooxygenase‐2 (COX‐2) and its metabolic product prostaglandin E2 (PGE2) are induced in response to growth factors, inflammatory cytokines, tumor promoters, activated oncogenes, and, in the skin, ultraviolet (UV) radiation. Accumulating evidence suggests a role for the COX‐2/PGE2 pathway in tumorigenesis in various tissue types including cutaneous squamous cell carcinoma. There is also strong evidence for a role in the development of actinic keratoses (AKs) — common dysplastic lesions of the skin associated with UV radiation overexposure — considered as part of a continuum with skin cancer. Non‐steroidal anti‐inflammatory drugs (NSAIDs) exert their anti‐inflammatory, analgesic, and antipyretic effects by reversibly or irreversibly acetylating COX isoforms, inhibiting downstream prostaglandins, and may have a chemopreventive role in malignancies, including skin cancer. Topical treatment of AK lesions with the NSAID diclofenac sodium 3% in combination with hyaluronic acid 2.5% has been shown to be effective and well tolerated, although the mechanism of action remains to be elucidated.
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Affiliation(s)
- Gareth J Thomas
- Cancer Sciences Unit, University of Southampton, Southampton, United Kingdom
| | - Pedro Herranz
- Department of Dermatology, La Paz University Hospital, Madrid, Spain
| | | | - Aurora Parodi
- DISSAL Section of Dermatology, University of Genoa-IRCCS, AOU San Martino-IST, Genoa, Italy
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Maarouf M, Kromenacker BW, Brucks ES, Hendricks A, Shi VY. Reducing unpleasant side effects of topical 5-Fluorouracil treatment for actinic keratosis: a randomized controlled trial. J DERMATOL TREAT 2019; 31:175-179. [PMID: 30821548 DOI: 10.1080/09546634.2019.1589638] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Introduction: 5-Fluorouracil (5-FU) for prophylactic treatment of diffuse actinic keratosis results in an exuberant inflammatory reaction, contributing to patient noncompliance and dissatisfaction.Design: This 5-week split-faced, double-blind, randomized controlled trial involved 30 subjects with diffuse facial AK who received twice daily 5-FU treatment for 2 weeks. This was followed by pre-randomized twice daily use of one of three topical interventions on one half of the face. TEWL, pH, and hydration were assessed on each quadrant of the face at all visits. Additionally, photographs were subjectively graded by three blinded trained observers.Results: Thirty subjects were enrolled, and had an average 27.1 (SD 11.8, range: 13-62) palpable AKs at baseline. Average resolution of baseline AK count was 98.1% by week 4. Clobetasol propionate is best at decreasing TEWL (p = .034), while petrolatum jelly most significantly improves hydration (p = .019) and erythema (p = .014). Though controlled release skin barrier emulsion trended towards improvement in TEWL (p = .17) and hydration (p = .19), there was no significant decrease in erythema (p = .257). Patient free-text response identified erythema as the most bothersome symptom.Conclusions: Given the low cost, wide availability, and ability to significantly reduce erythema, petrolatum should be used for post-5-FU treatment for diffuse AK.
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Affiliation(s)
- Melody Maarouf
- College of Medicine, University of Arizona, Tucson, AZ, USA
| | | | - Eric S Brucks
- Department of Medicine, University of Arizona, Tucson, AZ, USA
| | | | - Vivian Y Shi
- Department of Medicine, Division of Dermatology, University of Arizona, Tucson, AZ, USA
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Moayedi Y, Greenberg SA, Jenkins BA, Marshall KL, Dimitrov LV, Nelson AM, Owens DM, Lumpkin EA. Camphor white oil induces tumor regression through cytotoxic T cell-dependent mechanisms. Mol Carcinog 2019; 58:722-734. [PMID: 30582219 DOI: 10.1002/mc.22965] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 12/18/2018] [Accepted: 12/20/2018] [Indexed: 12/11/2022]
Abstract
Bioactive derivatives from the camphor laurel tree, Cinnamomum camphora, are posited to exhibit chemopreventive properties but the efficacy and mechanism of these natural products are not fully understood. We tested an essential-oil derivative, camphor white oil (CWO), for anti-tumor activity in a mouse model of keratinocyte-derived skin cancer. Daily topical treatment with CWO induced dramatic regression of pre-malignant skin tumors and a two-fold reduction in cutaneous squamous cell carcinomas. We next investigated underlying cellular and molecular mechanisms. In cultured keratinocytes, CWO stimulated calcium signaling, resulting in calcineurin-dependent activation of nuclear factor of activated T cells (NFAT). In vivo, CWO induced transcriptional changes in immune-related genes identified by RNA-sequencing, resulting in cytotoxic T cell-dependent tumor regression. Finally, we identified chemical constituents of CWO that recapitulated effects of the admixture. Together, these studies identify T cell-mediated tumor regression as a mechanism through which a plant-derived essential oil diminishes established tumor burden.
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Affiliation(s)
- Yalda Moayedi
- Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, New York
| | - Sophie A Greenberg
- Department of Dermatology, Columbia University Irving Medical Center, New York, New York
| | - Blair A Jenkins
- Medical Scientist Training Program, Columbia University Irving Medical Center, New York, New York
| | - Kara L Marshall
- Department of Dermatology, Columbia University Irving Medical Center, New York, New York
| | - Lina V Dimitrov
- Program in Neuroscience and Behavior, Barnard College, Columbia University, New York, New York
| | - Aislyn M Nelson
- Department of Dermatology, Columbia University Irving Medical Center, New York, New York.,Department of Neuroscience, Baylor College of Medicine, Houston, Texas
| | - David M Owens
- Department of Dermatology, Columbia University Irving Medical Center, New York, New York.,Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York
| | - Ellen A Lumpkin
- Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, New York.,Department of Dermatology, Columbia University Irving Medical Center, New York, New York
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Salido-Vallejo R, González-Velasco M, Guilabert M, García EI, Mira JJ. [The perception of care received by patients with actinic keratosis]. J Healthc Qual Res 2018; 33:360-369. [PMID: 30497970 DOI: 10.1016/j.jhqr.2018.09.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 07/30/2018] [Accepted: 09/03/2018] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To analyse barriers limiting an integral approach in the care process of patients with actinic keratosis, and to validate a questionnaire of their perception in order to assess this approach. METHOD A qualitative study (Focus Group) was conducted to assess the perception of the healthcare process of professionals (dermatologists, family doctors, nurses, pharmacists and managers), and patients. A validation study of a new tool was conducted, defining the scope and contents of a questionnaire of perceived quality. Reliability, consistency and validity were analysed after inviting a convenience sample of 225 patients to respond. RESULTS Underdiagnosis in primary care, a higher variability in resources, and access to the health care circuit, together with gaps in patient information about actinic keratosis, are relevant barriers to achieve comprehensive care in this disease condition. The result of the focus groups advised to elaborate 14 reactive items. A total of 224 patients responded (mean age 71.6, SD 11.1), of which 153 (68%) were men. Two factors were isolated including 12 items (explained variance of 58%). The consistency of this factorial solution was .87, the split-half reliability being .76, with the scores in the factors showing an adequate predictive capacity. CONCLUSIONS The coordination between levels and to reduce to variability in equipment and clinical decision making in Primary Care are the most prominent barriers. The questionnaire has appropriate metric properties and it explores the information and care by the medical staff and the information and advice provided by the pharmacist.
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Affiliation(s)
| | - M González-Velasco
- Vocalía de Dermofarmacia del Colegio Oficial de Farmacéuticos de Sevilla, Sevilla, España
| | - M Guilabert
- Universidad Miguel Hernández, Elche, España.
| | | | - J J Mira
- Universidad Miguel Hernández, Elche, España; Departamento de Salud Alicante Sant Joan, Alicante, España; Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), España
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Reinhold U, Petering H, Dirschka T, Rozsondai A, Gille J, Kurzen H, Ostendorf R, Ebeling A, Stocker M, Radny P. Photodynamic therapy with a 5‐ALA patch does not increase the risk of conversion of actinic keratoses into squamous cell carcinoma. Exp Dermatol 2018; 27:1399-1402. [DOI: 10.1111/exd.13804] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 09/27/2018] [Accepted: 10/11/2018] [Indexed: 11/30/2022]
Affiliation(s)
| | | | | | | | | | | | | | | | | | - Peter Radny
- Dermatology Practice Friedrichshafen Germany
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Calzavara-Pinton P, Tanova N, Hamon P. Evaluation of the treatment costs and duration of topical treatments for multiple actinic keratosis based on the area of the cancerization field and not on the number of lesions. J Eur Acad Dermatol Venereol 2018; 33:312-317. [DOI: 10.1111/jdv.15269] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 09/19/2018] [Indexed: 11/29/2022]
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Stockfleth E, Hofbauer G, Reinhold U, Popp G, Hengge U, Szeimies R, Brüning H, Anliker M, Hunger T, Dummer R, Ulrich C, Kenzelmann R, Surber C, French L. Topical resiquimod dosing regimens in patients with multiple actinic keratoses: a multicentre, partly placebo‐controlled, double‐blind clinical trial. Br J Dermatol 2018; 180:297-305. [DOI: 10.1111/bjd.17124] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/20/2018] [Indexed: 12/13/2022]
Affiliation(s)
- E. Stockfleth
- Universitätshautklinik, St. Josef‐Hospital Gudrunstrasse 56 44791 Bochum Germany
| | - G.F.L. Hofbauer
- Dermatologische Klinik UniversitätsSpital Zürich Gloriastrasse 31 8091 Zürich Switzerland
| | - U. Reinhold
- Medizinisches Zentrum Bonn‐Friedensplatz Fachbereich Dermatologie Allergologie, Dermatologische Onkologie Friedensplatz 16 53111 Bonn Germany
| | - G. Popp
- Licca Clinical Research Institute Hofackerstrasse 19 86179 Augsburg Germany
| | - U.R. Hengge
- Hautzentrum Prof. Hengge Immermannstrasse 10 40210 Düsseldorf Germany
| | - R.M. Szeimies
- Klinikum Vest GmbH Knappschaftskrankenhaus, Abteilung Dermatologie Dorstener Strasse 151 45657 Recklinghausen Germany
| | - H. Brüning
- DERMAKIEL Allergie und Hautzentrum Schönberger Strasse 72–74 24148 Kiel Germany
| | - M. Anliker
- Dermatologie/Allergologie Kantonsspital St. Gallen Roschacher Strasse 95 9007 St. Gallen Switzerland
| | - T. Hunger
- Dermatologische Klinik Inselspital, Universitätsspital Bern Freiburgerstrasse 3 3010 Bern Switzerland
| | - R. Dummer
- Dermatologische Klinik UniversitätsSpital Zürich Gloriastrasse 31 8091 Zürich Switzerland
| | - C. Ulrich
- Hauttumorzentrum Charité (HTCC) Klinik für Dermatologie, Venerologie und Allergologie, Campus Charité Mitte, Charité – Universitätsmedizin Berlin Charitéplatz 1 10117 Berlin Germany
| | - R. Kenzelmann
- Galderma Spirig Pharma AG Froschackerstrasse 6 4622 Egerkingen Switzerland
| | - C. Surber
- Dermatologische Klinik UniversitätsSpital Zürich Gloriastrasse 31 8091 Zürich Switzerland
- Dermatologische Klinik Universitätsspital Basel Petersgraben 4 4031 Basel Switzerland
| | - L.E. French
- Dermatologische Klinik UniversitätsSpital Zürich Gloriastrasse 31 8091 Zürich Switzerland
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Reygagne P, Rostain G. Au-delà des kératoses actiniques, le champ de cancérisation cutané. Ann Dermatol Venereol 2018; 145:587-592. [DOI: 10.1016/j.annder.2018.06.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 04/24/2018] [Accepted: 06/20/2018] [Indexed: 12/11/2022]
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Wee E, Wolfe R, Mclean C, Kelly JW, Pan Y. Clinically amelanotic or hypomelanotic melanoma: Anatomic distribution, risk factors, and survival. J Am Acad Dermatol 2018; 79:645-651.e4. [PMID: 30241625 DOI: 10.1016/j.jaad.2018.04.045] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 04/13/2018] [Accepted: 04/19/2018] [Indexed: 02/09/2023]
Abstract
BACKGROUND The recognition and diagnosis of clinically amelanotic or hypomelanotic melanoma is a challenge. OBJECTIVE This study aimed to examine the anatomic distribution and risk factors associated with clinically amelanotic or hypomelanotic melanoma and compare the survival of patients with clinically amelanotic or hypomelanotic melanoma with that of patients with pigmented melanoma. METHODS A prospective cohort study of all cases of primary invasive melanoma managed at a tertiary referral center was performed. RESULTS There were a total of 3913 invasive melanomas, and 384 (9.8%) were clinically amelanotic or hypomelanotic. Skin phototype I; red as well as blonde hair color; actinic keratoses; nodular, desmoplastic, and lentigo maligna subtype; increased Breslow thickness; and mitoses were independently associated with amelanotic or hypomelanotic melanoma (P < .05). After adjustment for subtype and thickness, the face, ears, lateral aspect of the neck, upper portion of the arm, posterior aspect of the forearm, dorsal aspect of the hand, and anterior aspect of the lower portion of the leg were associated with increased odds of amelanotic or hypomelanotic melanoma when compared with the upper portion of the back (P < .05). Mortality risk from melanoma appeared greater for amelanotic or hypomelanotic melanoma than for pigmented melanoma (hazard ratio, 1.5; 95% confidence interval, 1.1-2.1) but was similar once Breslow thickness was taken into account. LIMITATIONS Single tertiary referral center. CONCLUSION Although clinically amelanotic or hypomelanotic melanoma can occur on all body sites, it is more common on chronically sun-exposed areas. Clinicians should have an increased index of suspicion in patients with a sun-sensitive skin phenotype, red hair, and associated actinic keratoses.
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Affiliation(s)
- Edmund Wee
- Victorian Melanoma Service, Alfred Health, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
| | - Rory Wolfe
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - Catriona Mclean
- Victorian Melanoma Service, Alfred Health, Melbourne, Australia
| | - John W Kelly
- Victorian Melanoma Service, Alfred Health, Melbourne, Australia
| | - Yan Pan
- Victorian Melanoma Service, Alfred Health, Melbourne, Australia
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Rubas K, Maj J. What should a cosmetologist know about dermatological lesions on the face? MEDICAL SCIENCE PULSE 2018. [DOI: 10.5604/01.3001.0012.6197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
In everyday practice, cosmetologists often observe abnormalities on the facial skin of his or her clients. Facial lesions have a diverse clinical picture, although most are benign. However, some lesions may be malignant and demand fast diagnosis and treatment. Among benign lesions are xanthomas, epidermal cysts, milia and seborrheic keratoses. Xanthomas are usually localized on the eyelids and often coexist with dyslipidemia. They appear clinically as yellowish papules that vary in size. Epidermal cysts are the most common type of skin cyst. They typically occur on the head and neck, and usually affect young adults in their 20s. Milia are common skin lesions that are typically numerous in presence and appear as small-sized sebaceous papules. Seborrheic keratoses are another important type of lesion that are localized on the face and may be disturbing for clients. These are benign tumors that usually appear in individuals over 50 years of age and have an incidence that rises with age. Typically, they are brown in color but they can also be other colors including black, yellow, grey or bluish.
Other skin changes include basal cell carcinoma, actinic keratosis, squamous cell carcinoma and lentiginous malignant melanoma. Basal cell carcinoma is a slow-growing, locally malignant epithelial cancer of the skin. This cancer presents mainly in areas exposed to ultraviolet (UV) radiation. Actinic keratosis is a pre-cancerous lesion that is associated with UV radiation. It predisposes to squamous cell carcinoma and other skin cancers rarely. In contrast to basal cell carcinoma, squamous cell carcinoma may cause metastases with high mortality. Melanoma on the head and face usually takes the form of a lentiginous malignant melanoma. This manifests clinically as a brown spot that slowly grows centrifugally. Melanomas vary in size and color. Dermoscopy is an important tool that may help during diagnosis of facial lesions.
Given the severe consequences of some skin lesions, it is very important for cosmetologists to have knowledge of the conditions described above. This is because he or she is often the first person who can persuade the client to undergo further diagnosis.
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Affiliation(s)
- Klaudia Rubas
- Department and Clinic of Dermatology, Venerology and Allergology, Wroclaw Medical University
| | - Joanna Maj
- Department of Cosmetology, Opole Medical School, Opole, Poland
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RETRACTED: Management of seborrhoeic keratosis and actinic keratosis with an erbium:YAG laser-experience with 547 patients. Int J Oral Maxillofac Surg 2018; 48:902-907. [PMID: 30193758 DOI: 10.1016/j.ijom.2018.08.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 08/13/2018] [Accepted: 08/17/2018] [Indexed: 11/22/2022]
Abstract
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).
This article has been retracted at the request of the Editors because the photograph in Figure 1b was a duplicate image of Figure 1a, but with the keratosis removed, and did not represent the surgery that was described in the article. The authors apologise for this error.
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