Journal of Clinical and Aesthetic Dermatology

Ingenol Mebutate Topical Gel 2016

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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S4 JCAD journal of clinical and aesthetic dermatology November 2016 • Volume 9 • Number 11 disorders, such as nonmelanoma skin cancers (NMSCs), human papillomavirus (HPV)-associated lesions, and others. Author commentary is also included with emphasis placed on rational application in clinical practice. Nonmelanoma Skin Cancer Skin cancer remains the most prevalent malignancy in the United States, with a conservative annual estimate of more than 3.5 million cases in greater than 2 million people. 4 NMSCs, especially basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), comprise the vast majority of skin malignancies. 4,13 Superficial forms of NMSC are common and predominantly include SCC in-situ, often referred to as Bowen's disease, and superficial BCC, sometimes referred to as multifocal BCC. 14 Optimal management of both BCC and SCC, including their superficial forms, depends on several factors, including the age and medical status of the patient, tumor location, tumor size, histologic pattern of the neoplasm, history of any previous therapy, and patient preference; available therapeutic options for BCCs and SCCs include a variety of surgical, medical, and physical modality options. 15–17 Topical therapies for primarily superficial forms of BCC and/or SCC, including with 5-FU, imiquimod, diclofenac, and photodynamic therapy (PDT) have been reported. 15–20 Ingenol mebutate use in NMSC. The short-term and long-term efficacy of IMG for treatment of AKs is well- established and supported by suggested modes of action that have been reported in the literature. 1,3–12 These same modes of action provide rational support for the use of IMG for selected presentations of BCC and/or SCC, especially their superficial forms that are based on histologic characteristics. 4,11,21 With use of an advanced imaging technique called optical coherence tomography (OCT), combined with histologic confirmation by skin biopsy, evaluation of clinically diagnosed AKs and subclinical AKs including areas of perilesional skin confirmed the efficacy of IMG as compared to untreated sites. 22 Two important observations from this study are 1) some clinically diagnosed AK sites proved to be SCC in-situ histologically and by OCT, and 2) normal-appearing perilesional skin commonly exhibits subclinical AKs, confirmed histologically and by OCT. These results support the need for field-type management of AK and SCC in-situ. 22 TABLE 1. Ingenol mebutate suggested modes of action* DIRECT C Y TOTOXIC CHEMOABLATION • Rapid disruption of plasma membrane with subsequent swelling of mitochondria resulting in primary necrosis INFLAMMATORY RESPONSE • Local recruitment of neutrophils via direct effect on endothelial cells, which increases the expression of vascular adhesion receptors • Transendothelial migration of leukocytes via indirect effect of chemokine activation and induction of a chemotactic gradient ANTIBODY PRODUCTION • Increased levels of anti-tumor antibodies, which enhances cytotoxicity synergistically ACTIVATION OF PROTEIN KINASE C ENZYMES • Potential association with inflammatory response *Lebwohl M, Sohn A. Expert Rev Dermatol. 2012;7(2):121–128

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