{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:55:04Z","timestamp":1791276904646,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,7,25]],"date-time":"2016-07-25T00:00:00Z","timestamp":1469404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,7,25]],"date-time":"2016-07-25T00:00:00Z","timestamp":1469404800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Actinic keratosis (\n                      <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>\n                      ) is a cutaneous intraepithelial neoplasm that typically develops on sun\u2010damaged skin. The incidence of\n                      <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>\n                      is increasing worldwide, and it is accepted as the most frequent pre\u2010malignant lesion in humans.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To demonstrate that ingenol mebutate gel is effective in the treatment of actinic keratoses because of its clinical, dermoscopic, capillaroscopic, histopathological and immunohistochemical treatment outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sixty individuals with multiple non\u2010hypertrophic\n                      <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>\n                      s were enrolled into this non\u2010randomized, open\u2010label, prospective, trial. Acquisition of clinical, dermoscopic and capillaroscopic images at baseline (T0), immediately after treatment on 3\n                      <jats:sup>rd<\/jats:sup>\n                      (trunk and\/or extremities) or 4\n                      <jats:sup>th<\/jats:sup>\n                      (scalp and\/or face) day (T1), 14 days after the end of the treatment (T2) and at 60 days (T3). A subgroup of 20 patients received a cutaneous biopsy both at baseline and at T3 for histological and immunohistochemical evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinical improvement was observed in 100% of cases: total clearance in 41 patients (68.3%); partial clearance in 19 patients (32.7%). After treatment, dermoscopic improvement of all non\u2010pigmented and pigmented\n                      <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>\n                      lesions was observed. Most of the dermoscopic features disappeared with treatment. Total disappearance of specific vascular structures or significant reduction in the number and calibre of new blood vessels was capillaroscopically observed in all patients analysed (\n                      <jats:italic>P<\/jats:italic>\n                      \u2264 0.001). The immunohistochemical expression of p63 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.002), Ki\u201067 (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.015) and\n                      <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.016) significantly decreased.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The clinical efficacy of ingenol mebutate on\n                      <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>\n                      s is confirmed by its effect on angiogenesis, stem cell activity and cell proliferation\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n   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