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The efficacy of encorafenib plus binimetinib (E + B) combination therapy for BRAF-mutated advanced melanoma as second-line therapy and beyond is still unknown. In this report, we investigated 22 cases of BRAF-mutated advanced melanoma treated with E + B combination therapy. The objective response rate (ORR) for the total cohort was 68.4%. Notably, the ORR for the second-line and beyond cohort was 73.3%, suggesting that the therapeutic effect of E + B combination therapy is comparable with that of first-line targeted therapy. In contrast, overall survival and progress-free survival in our present cohort was worse than that in a previous clinical trial. Notably, although the incidence rate of severe adverse events was higher than that in a previous report, our present study suggested that E + B combination therapy is a well-tolerated antimelanoma regimen. Our present study suggested that the efficacy and safety profile of E + B combination therapy as a second-line therapy and beyond is comparable with that of first-line targeted therapy.

The Japanese Dermatological Association prepared the clinical guidelines for the "Wound, pressure ulcer and burn guidelines", second edition, focusing on treatments. Among them, "Guidelines for wounds in general" is intended to provide the knowledge necessary to heal wounds, without focusing on particular disorders. It informs the basic principles of wound treatment, before explanations are provided in individual chapters of the guidelines. We updated all sections by collecting references published since the publication of the first edition. In particular, we included new wound dressings and topical medications. Additionally, we added "Question 6: How should wound-related pain be considered, and what should be done to control it?" as a new section addressing wound pain, which was not included in the first edition.

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.

Anti-programmed death 1 antibody monotherapy is a first-line and widely used immunotherapy for the treatment of advanced melanoma. However, its efficacy rate is lower in the Japanese population compared with the Caucasian population. Ipilimumab is another immune checkpoint inhibitor (ICI) that activates and increases T cells, which suppress the function of regulatory T cells. Previous reports have suggested that ipilimumab is useful for treating advanced melanoma, particularly in combination with radiation therapy. In this report, we described three cases of nivolumab-resistant melanoma successfully controlled by ipilimumab with intensity-modulated radiotherapy, which may enhance the therapeutic effects of the sequential administration of ICI.

"Wound, pressure ulcer and burn guidelines - 6: Guidelines for the management of burns, second edition" is revised from the first edition which was published in the Japanese Journal of Dermatology in 2016. The guidelines were drafted by the Wound, Pressure Ulcer and Burn Guidelines Drafting Committee delegated by the Japanese Dermatological Association, and intend to facilitate physicians' clinical decisions in preventing, diagnosing and treating burn injury. All sections are updated by collecting documents published since the publication of the first edition. Especially, the recommendation levels of dressing materials newly covered by the Japanese national health insurance are mentioned. In addition, the clinical questions (CQ) regarding the initial treatment of electrical (CQ15) and chemical burns (CQ16), and also the use of escharotomy (CQ22), are newly created.

Because the efficacy rates of monotherapy with immune checkpoint inhibitors such as nivolumab or ipilimumab are not sufficient, to enhance the antitumor effects of these reagents is of great interest among dermato-oncologists. In this report, we describe two cases of multiple in-transit metastatic melanomas on the leg successfully treated with intensity-modulated radiotherapy (IMRT) using a CyberKnife in combination with ipilimumab or nivolumab. Our cases suggested that IMRT could enhance the antitumor effects of immune checkpoint inhibitors in patients with multiple in-transit melanomas.

The Japanese Dermatological Association determined to prepare the Wound/Burn Guidelines focusing on treatments, catering to needs for the clinical practice of dermatology. Among these guidelines, "Wounds in General" was intended to explain knowledge necessary "to heal wounds" without specifying particular disorders.

The Wound/Burn Guidelines Committee consists of members commissioned by the Board of Directors of the Japanese Dermatological Association (JDA). It held several meetings and evaluations in writing since October 2008, and drafted five guidelines for the diagnosis and treatment including commentaries on wounds in general and the Guidelines for the Diagnosis and Treatment for Pressure Ulcers by taking opinions of the Scientific Committee and Board of Directors of JDA into consideration.

Although therapies for advanced melanoma have been greatly improved by the development of immune checkpoint inhibitors and BRAF/mitogen-activated protein kinase kinase inhibitors, there are still many concerns about the administration of these novel drugs. Therefore, to combine these therapies sequentially at appropriate time points of the disease is important. In this report, we report two cases in which dabrafenib and trametinib therapy for advanced melanoma failed but were successfully controlled by nivolumab monotherapy, and investigated the sera sCD163, CCL22 and CXCL10 as biomarkers for tumor progression. Interestingly, the sera levels of sCD163, CXCL10 and CCL22, both of which are produced by activated tumor-associated macrophages, were increased in parallel with the tumor progression in each case. Because this report presents only two cases, further data will need to be accumulated to provide more fundamental insights into the usefulness of these biomarkers for predicting disease progression in melanoma.

Burns are a common type of skin injury encountered at all levels of medical facilities from private clinics to core hospitals. Minor burns heal by topical treatment alone, but moderate to severe burns require systemic management, and skin grafting is often necessary also for topical treatment. Inappropriate initial treatment or delay of initial treatment may exert adverse effects on the subsequent treatment and course. Therefore, accurate evaluation of the severity and initiation of appropriate treatment are necessary. The Guidelines for the Management of Burn Injuries were issued in March 2009 from the Japanese Society for Burn Injuries as guidelines concerning burns, but they were focused on the treatment for extensive and severe burns in the acute period. Therefore, we prepared guidelines intended to support the appropriate diagnosis and initial treatment for patients with burns that are commonly encountered including minor as well as moderate and severe cases. Because of this intention of the present guidelines, there is no recommendation of individual surgical procedures.

Varicose veins are treated at multiple clinical departments, but as patients often visit the dermatology clinic first due to leg ulcers, the present Guidelines for the Management of Lower Leg Ulcers/Varicose Veins were prepared in consideration of the importance of the dermatologist's role. Also, the disease concept of chronic venous insufficiency or chronic venous disorders and the CEAP classification of these disorders are presented. The objective of the present guidelines is to properly guide the diagnosis and treatment of lower leg ulcers/varicose veins by systematically presenting evidence-based recommendations that support clinical decisions.

The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.

Because nivolumab significantly prolongs survival in patients with metastatic melanoma, enhancing its antitumor immune response is of great interest to dermato-oncologists. In this report, we describe two cases of metastatic melanoma successfully treated with nivolumab in combination with contact immunotherapy, using contact sensitizing agents, such as squaric acid dibutylester and diphencyprone. In addition, immunohistochemical staining supported one of the possible mechanisms of this combination therapy. Our present cases suggested a possible therapy for metastatic melanoma using nivolumab in combination with contact immunotherapy.

We report a 65-year-old Japanese woman who presented with a nodule on the nose near the left eye. Histological examination of the totally resected lesion revealed the typical features of necrobiotic xanthogranuloma (NXG). However, her laboratory investigation revealed no paraproteinemia. We believe that the present case represents a cutaneous variant of NXG without accompaniment of paraproteinemia or any systemic involvement.

In order to improve the oxidative stability of hydroquinone (HQ), the only depigmenting agent available clinically for skin, 14 hydroquinone fatty acid esters (HQ-Rs) were synthesized and examined for their stability, efficacy, and intradermal metabolism. HQ-Rs containing more than 3 carbon atoms in the fatty acid side chain showed excellent stability in an aqueous base (pH 6). HQ-Rs containing fewer than 8 carbon atoms in the fatty acid side chain exhibited skin depigmenting potencies better than that of HQ. HQ-R was quantitatively hydrolyzed by a skin homogenate to liberate HQ. The hydrolysis velocity of the HQ-Rs was dependent on the length of the fatty acid side chain; the longer the length, the slower the hydrolysis velocity. From these results, we concluded that HQ-R is absorbed into the skin after topical application, hydrolyzed by esterase, and it depigments the skin by liberating HQ. Thus, HQ-R function as a prodrug of HQ; it exhibits both an excellent oxidative stability and an excellent skin depigmenting potency by liberating HQ within the skin.