Publications by authors named "Isei T"

"Wound, Pressure Ulcer, and Burn Guidelines-5: Guidelines for the management of lower leg ulcers and varicose veins, second edition" is revised from the first edition, which was published in the Japanese Journal of Dermatology in 2011. 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 management of lower leg ulcers and varicose veins. We updated all sections by collecting documents published since the publication of the first edition.

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  • The study focused on the genetic changes in extramammary Paget disease (EMPD), specifically looking at CDKN2A and MTAP alterations and their impact on disease progression.
  • Researchers analyzed 24 invasive/metastatic EMPD cases using immunohistochemistry and DNA sequencing, finding that p16 expression was mostly preserved in early-stage tumors but significantly lost in invasive and metastatic stages.
  • The study confirmed CDKN2A deletions in all five metastatic cases tested, suggesting that loss of p16 expression and CDKN2A alterations are common in aggressive forms of EMPD.
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Avelumab, a programmed cell death ligand 1 blocking antibody, was approved for its first indication in Japan in September 2017 to treat unresectable Merkel cell carcinoma (MCC). Given that the pivotal JAVELIN Merkel 200 study only included a few Japanese patients, this post-marketing surveillance (PMS) evaluated the safety and effectiveness outcomes of patients with MCC who received avelumab in general clinical practice in Japan. This prospective, non-comparative, multicenter PMS included data from all patients with unresectable MCC who received avelumab between November 22, 2017 (avelumab launch date) and October 31, 2019.

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  • The study focused on the effectiveness of salvage therapies in Japanese patients with advanced acral melanoma (AM) after they failed PD-1 monotherapy, a common treatment for melanoma.
  • 108 patients were analyzed, receiving various treatments such as ipilimumab, nivolumab plus ipilimumab, or cytotoxic chemotherapy, with varying objective response rates (ORR) and overall survival (OS) outcomes.
  • Results indicated that while the combination of nivolumab and ipilimumab showed the longest median OS, it was not significantly more effective than other treatments, and nail apparatus melanoma patients had poorer survival outcomes compared to those with palm and sole melanoma.
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  • Anti-PD-1 immunotherapy is less effective for Asian patients with advanced BRAF V600-mutant melanoma, leading researchers to consider alternative first-line treatments.
  • A study analyzed treatment outcomes for 336 Asian patients using BRAF/MEK inhibitors, anti-PD-1, and PD-1/CTLA-4 combinations, revealing BRAF/MEKi had the best objective response rates and progression-free survival.
  • The results suggested that BRAF/MEKi may be preferred over anti-PD-1 treatments for these patients, particularly in second-line settings, highlighting the need for tailored treatment approaches based on patient demographics.
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Background: The clinicopathologic and genetic features of cutaneous melanoma with a BRAF V600K mutation are not well-known. We aimed to evaluate these characteristics in comparison with those associated with BRAF V600E.

Methods: Real-time polymerase chain reaction (PCR) and/or the MassARRAY® system were used to detect BRAF V600K in 16 invasive melanomas and confirm BRAF V600E in another 60 cases.

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Background: Efficacy of anti-PD-1 antibody monotherapy (PD1) or anti-PD-1 plus anti-CTLA-4 combination therapy (PD1 +CTLA4) for melanoma is affected by its clinical subtype. The amount of tumor mutation burden (TMB) caused by cumulative sun damage (CSD) is occasionally used to explain this; however, their relationship in Japanese nonacral cutaneous melanoma (NACM) is still unclear.

Objective: To analyze the ICI efficacy and its relationship with CSD of the primary lesion in Japanese patients with NACM.

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Background And Aim: To investigate the outcomes in eight Japanese patients with cancer treated with mycophenolate mofetil (MMF) and corticosteroids for immune checkpoint inhibitor treatment-induced severe immune-related hepatitis (ir-hepatitis) and the efficacy and safety of MMF.

Methods: We retrospectively examined patient background, treatment course, as well as examination and imaging data using electronic medical records.

Results: The ratio of male to female patients was 7:1, and the median age was 60 years (27-72 years).

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An increasing number of patients with cancer are being treated with immune checkpoint inhibitors. Consequently, the incidence of immune checkpoint inhibitor-related myocarditis has been increasing. Nonetheless, the diagnostic criteria for the immune checkpoint inhibitor-related myocarditis have not been sufficiently established.

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Background: Although anti-PD-1 antibody monotherapy (PD-1) is commonly used to treat advanced acral melanoma (AM), its efficacy is limited. Further, data on the efficacy of PD-1 plus anti-CTLA-4 antibody (PD-1+CTLA-4) for the treatment of AM are limited. Therefore, we compared the efficacy of PD-1+CTLA-4 and PD-1 in the treatment of Japanese patients with advanced AM.

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Mammals express a wide variety of glycans that include N-glycans, O-glycans, proteoglycans, glycolipids, etc. Glycan expression can modulate the cellular functions, and hence is strongly involved in the onset and progression of numerous diseases. Here, we report the relevance of the ectopic expression of keratan sulfate (KS) glycan chains in human malignant melanomas.

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  • Talimogene laherparepvec (T-VEC) is a treatment approved for unresectable melanoma in several countries, and this study specifically looked at its effectiveness and safety in Japanese patients with advanced melanoma stages IIIB-IV.
  • The study included 18 patients, most of whom had received prior therapies, and involved injecting T-VEC into tumors, with a focus on monitoring for dose-limiting toxicities and durable response rates.
  • Results indicated no major toxicities, with a high rate of adverse events reported (94.4%), but only 2 patients (11.1%) showed a durable response of 6 months or longer, aligning with findings from similar studies on T-VEC in other populations.
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Basal cell carcinoma is the most common type of skin cancer, and surgical excision with clear margins is the standard of care. Surgical margins are determined based on risk factors (high or low risk) for recurrence according to the National Comprehensive Cancer Network and Japanese basal cell carcinoma guidelines. The clarity of the clinical tumor border (well-defined or poorly defined) is considered a risk factor, and significant discrepancies in the judgment of clinical tumor borders among dermato-oncologists may occur.

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This study sought to confirm the homogeneity of BRAF V600E mutation status in melanoma. BRAF immunohistochemistry was performed on 102 lesions from 60 patients of melanoma with BRAF V600E mutation and 38 negative-control melanoma lesions from 38 patients, both of which were confirmed by real-time PCR or the MassARRAY System. In the positive-control lesions, 9 lesions from 7 patients with preceding BRAF-inhibitor therapy were included.

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Background: Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited.

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Background: Immune checkpoint inhibitors (ICIs) have a lower efficacy in mucosal melanoma (MUM) than in cutaneous melanoma. The use of combination treatments with radiotherapy (RT) to improve the efficacy in MUM, however, requires further investigation.

Methods: We retrospectively evaluated 225 advanced MUM patients treated with anti-PD-1 monotherapy (PD1; 115) or anti-PD-1 + anti-CTLA-4 combination therapy (PD1+CTLA4; 42) with or without RT (56 and 12, respectively).

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  • * The majority of cases were found in older males, with tumors primarily located on the ventral trunk and demonstrating specific histological characteristics and genetic mutations.
  • * Lymph node metastasis and advanced-stage disease were associated with larger tumor sizes, leading to a reclassification of LGNECS as sweat-gland carcinoma with neuroendocrine differentiation (SCAND) to better reflect its features.
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Aims: The aim of this study was to determine the clinicopathological and genetic characteristics of axillary signet-ring cell/histiocytoid carcinoma (SRCHC) and the relationship between axillary SRCHC, eyelid SRCHC, and conventional apocrine carcinoma (AC).

Methods And Results: Eleven cases of axillary SRCHC, four cases of eyelid SRCHC, eight cases of axillary AC and five cases of invasive lobular carcinoma (ILC) were retrieved. Additionally, 14 axillary and 43 eyelid SRCHC cases from the literature were reviewed.

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The present study investigated outcomes of infliximab (IFX) treatment among 8 Japanese patients with various types of cancer (4 with malignant melanoma, 3 with lung cancer and 1 with renal cancer) who developed severe steroid-resistant immune-related adverse events (irAEs) in association with immune checkpoint inhibitors (ICIs) to determine its efficacy and safety. Information, including patient background, treatment progress, examination data and imaging data, was collected retrospectively from electronic medical records. Adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events version 4.

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Background And Aim: There exists no evidence on the relationship between endoscopic and histologic findings. Furthermore, even after multiple biopsy specimens were obtained, histologic examination usually fails to show the characteristic features of immune checkpoint inhibitor-associated colitis. In this study, we explored the endoscopic and histologic findings of immune checkpoint inhibitor-associated colitis.

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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.

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