Papers - UHARA Hisashi

悪性黒色腫における各種PD-L1抗体による染色性の差異についての検証

米田 大介, 加藤 潤史, 箕輪 智幸, 澤田 匡秀, 神谷 崇文, 宇原 久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  130 ( 5 ) 1248 - 1248  2020.05

コリン性蕁麻疹における定期的な発汗刺激の有効性に関する後方視的検討

箕輪 智幸, 澄川 靖之, 菅 裕司, 神谷 崇文, 宇原 久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  130 ( 5 ) 1217 - 1217  2020.05

Genetic analyses of mosaic neurofibromatosis type 1 with giant café-au-lait macule, plexiform neurofibroma and multiple melanocytic nevi.

Tokimasa Hida, Masashi Idogawa, Masae Okura, Shintaro Sugita, Taro Sugawara, Yasushi Sasaki, Takashi Tokino, Toshiharu Yamashita, Hisashi Uhara

The Journal of dermatology   47 ( 6 ) 658 - 662  2020.04  [Refereed]  [International journal]

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Neurofibromatosis type 1 (NF1) is a genodermatosis caused by heterozygous germ line variations in the NF1 gene. A second-hit NF1 aberration results in the formation of café-au-lait macules, cutaneous neurofibroma and plexiform neurofibroma (PNF). Mosaic NF1 (mNF1), caused by a postzygotic NF1 mutation, is characterized by localized or generalized NF1-related manifestations. Although NF1 and mNF1 are associated with pigmentary skin lesions, clinically recognizable melanocytic nevi that developed over PNF have not been reported. Here, we report the first case of multiple melanocytic nevi that developed on a giant café-au-lait macule and PNF. The PNF had biallelic NF1 deletions, a whole deletion of NF1 and a novel intragenic deletion involving exons 25-30. The deletions were not detected in the blood, which resulted in the diagnosis of mNF1. Furthermore, the nevus cells had not only biallelic NF1 deletions but also NRAS Q61R, a common mutation found in congenital melanocytic nevi. These analyses revealed the coexistence of the two different mosaic diseases, mNF1 and congenital melanocytic nevi. For a diagnosis of cases with atypical NF1-like symptoms, genetic analyses using blood and lesional tissues are useful and aid in genetic counseling.

DOI PubMed

Blastic plasmacytoid dendritic cell neoplasm(BPDCN)の2例

執行 延明, 西田 彩華, 菅野 莉英, 藤岡 茉生, 大橋 隆宏, 堀本 浩平, 加藤 潤史, 肥田 時征, 宇原 久, 村瀬 和幸, 井山 諭, 須釜 佑介, 前田 和男

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  130 ( 3 ) 418 - 418  2020.03

腹部に生じた巨大な尖圭コンジローマ

石田 倫子, 三苫 千景, 中原 真希子, 内 博史, 肥田 時征, 黄倉 真恵, 宇原 久, 古江 増隆

西日本皮膚科 ( 日本皮膚科学会-西部支部 )  82 ( 1 ) 3 - 4  2020.02

Successful therapy for diffuse cutaneous systemic sclerosis-induced digital ulcer treated with hyperbaric oxygen therapy.

Yuji Kan, Takafumi Kamiya, Ayako Kumagai, Yuna Hosokawa, Hisashi Uhara

The Journal of dermatology   47 ( 2 ) e62-e64  2020.02  [International journal]

DOI PubMed

Prognostic Factors and Long-Term Efficacy of Tonsillectomy in 17 Patients with Pustulotic Arthro-Osteitis.

Yuji Kan, Yasuyuki Sumikawa, Tokimasa Hida, Saeko Ajiki, Hisashi Uhara

The Eurasian journal of medicine   52 ( 1 ) 103 - 105  2020.02  [Refereed]  [International journal]

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In this case study, we aimed to evaluate the disease condition of patients with pustulotic arthro-osteitis (PAO) at 36-month post-tonsillectomy. A retrospective analysis of the cases of 17 patients with PAO who were resistant to initial systemic treatments and underwent tonsillectomy at our hospital in 2006-2016 was conducted. The patients' disease condition at 1-, 24-, and 36-month post-tonsillectomy was assessed by the visual analog scale (VAS) score for osteoarthropathic pain, the disease duration, the area of palmoplantar lesions, and the Palmoplantar Pustular Psoriasis Area Severity Index (ppPASI). In the minimum follow-up of 36-month post-tonsillectomy in 17 patients, the median ppPASI and VAS scores decreased from 12 to 1 and from 80 to 20, respectively. Thirteen patients with ≥70% improvement in their VAS scores maintained the same good condition after ≥36 months, whereas four patients with <70% improvement in their VAS scores did not show remarkable improvement after that time point. Furthermore, we found that the improvement in VAS score was not associated with the disease duration or the patients' pre-tonsillectomy ppPASI values. Tonsillectomy might be an alternative treatment option for patients with PAO. Long-term efficacy against pain can be predicted by evaluating a patient's improvement at 1-month post-tonsillectomy.

DOI PubMed

神経線維腫を伴わない神経線維腫症1型2家系の遺伝子解析

肥田 時征, 井戸川 雅史, 石川 亜貴, 水上 都, 加藤 潤史, 澄川 靖之, 時野 隆至, 宇原 久

日本レックリングハウゼン病学会学術大会プログラム・抄録集 ( 日本レックリングハウゼン病学会 )  11回   15 - 15  2020.02

Significance of 5-S-Cysteinyldopa as a Marker for Melanoma.

Kazumasa Wakamatsu, Satoshi Fukushima, Akane Minagawa, Toshikazu Omodaka, Tokimasa Hida, Naohito Hatta, Minoru Takata, Hisashi Uhara, Ryuhei Okuyama, Hironobu Ihn

International journal of molecular sciences   21 ( 2 )  2020.01  [Refereed]  [International journal]

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Melanoma is one of the most lethal and malignant cancers and its incidence is increasing worldwide, and Japan is not an exception. Although there are numerous therapeutic options for melanoma, the prognosis is still poor once it has metastasized. The main concern after removal of a primary melanoma is whether it has metastasized, and early detection of metastatic melanoma would be effective in improving the prognosis of patients. Thus, it is very important to identify reliable methods to detect metastases as early as possible. Although many prognostic biomarkers (mainly for metastases) of melanoma have been reported, there are very few effective for an early diagnosis. Serum and urinary biomarkers for melanoma diagnosis have especially received great interest because of the relative ease of sample collection and handling. Several serum and urinary biomarkers appear to have significant potential both as prognostic indicators and as targets for future therapeutic methods, but still there are no efficient serum and urinary biomarkers for early detection, accurate diagnosis and prognosis, efficient monitoring of the disease and reliable prediction of survival and recurrence. Levels of 5-S-cysteinyldopa (5SCD) in the serum or urine as biomarkers of melanoma have been found to be significantly elevated earlier and to reflect melanoma progression better than physical examinations, laboratory tests and imaging techniques, such as scintigraphy and echography. With recent developments in the treatment of melanoma, studies reporting combinations of 5SCD levels and new applications for the treatment of melanoma are gradually increasing. This review summarizes the usefulness of 5SCD, the most widely used and well-known melanoma marker in the serum and urine, compares 5SCD and other useful markers, and finally its application to other fields.

DOI PubMed

カルシフィラキシスにガス壊疽を合併した1例

小林 英理, 堀本 浩平, 西田 彩華, 執行 延明, 菅野 莉英, 箕輪 智幸, 藤岡 茉生, 肥田 時征, 宇原 久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  130 ( 1 ) 39 - 39  2020.01

発汗指導を行ったコリン性蕁麻疹12症例の検討

箕輪 智幸, 澄川 靖之, 菅 裕司, 兼古 理恵, 宇原 久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  130 ( 1 ) 80 - 80  2020.01

メルケル細胞癌に対してアベルマブ投与を行った2例

執行 延明, 細川 夕菜, 箕輪 智幸, 藤岡 茉生, 佐藤 さゆり, 堀本 浩平, 加藤 潤史, 肥田 時征, 宇原 久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  130 ( 1 ) 40 - 40  2020.01

中毒疹様皮疹を契機に診断に至った全身性エリテマトーデス(SLE)の1例

西田 彩華, 小林 英理, 細川 夕菜, 箕輪 智幸, 熊谷 綾子, 菅 裕司, 神谷 崇文, 宇原 久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  130 ( 1 ) 39 - 39  2020.01

Renal angiomyolipoma (AML) harboring a missense mutation of TSC2 with copy-neutral loss of heterozygosity (CN-LOH).

Masashi Idogawa, Tokimasa Hida, Toshiaki Tanaka, Noriaki Ohira, Shoichiro Tange, Yasushi Sasaki, Hisashi Uhara, Naoya Masumori, Takashi Tokino, Hiroshi Natori

Cancer biology & therapy     1 - 5  2019.12  [Refereed]  [International journal]

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Angiomyolipoma (AML) is classified as a perivascular epithelioid cell neoplasm, mostly occurring in the kidney. Twenty percent of patients with renal AML have tuberous sclerosis complex (TSC) caused by germline variation in the TSC1 or TSC2 gene. In this paper, we report the first case of renal AML harboring somatic missense mutations of the TSC2 gene and concomitant copy-neutral loss of heterozygosity (CN-LOH). The patient presented with solitary renal AML and pulmonary lymphangiomyomatosis and without other findings suggestive of TSC. Exome sequencing analysis of the renal AML, however, identified a pathogenic somatic missense mutation in the TSC2 gene (NM_000548:c.5228G>A:p. R1743Q), although no other somatic mutation was detected. Furthermore, no germline mutation in TSC1 or TSC2 was detected. Interestingly, the mutant allele ratio was too high for a somatic heterozygous mutation without loss of heterozygosity (LOH). Furthermore, no copy number variation was detected around the TSC2 locus (16p13.3). To clarify the allelic status, we analyzed heterozygous single-nucleotide polymorphisms (SNPs) in chromosome 16. In these SNPs, an unbalanced allele ratio was accumulated inside the 16p13.3 region. These results suggested copy-neutral LOH (CN-LOH). Consequently, we concluded that the missense mutation of the TSC2 gene and CN-LOH of the TSC2 locus caused renal AML.

DOI PubMed

Current clinical issue of skin lesions in patients with inflammatory bowel disease.

Tomoya Iida, Tokimasa Hida, Minoru Matsuura, Hisashi Uhara, Hiroshi Nakase

Clinical journal of gastroenterology   12 ( 6 ) 501 - 510  2019.12  [Refereed]  [Domestic journal]

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Inflammatory bowel disease (IBD) is associated with a number of extraintestinal complications, including skin lesions. Most reports have shown that skin lesions are found in 10-15% of IBD cases, although this depends on the definition of skin lesions. The representative skin lesions in patients with IBD are erythema nodosum, pyoderma gangrenosum, Sweet's syndrome, and so on. These lesions are often associated with IBD progression, and intestinal lesions in particular require appropriate treatment. Recently, another clinical issue regarding skin lesions in patients with IBD, a so-called paradoxical reaction, during the treatment with anti-tumor necrosis factor (TNF)-α agents has emerged. These reactions are termed paradoxical reactions because the skin lesions sometimes resemble psoriasis, although the anti-TNF-α agents have been historically used to treat psoriasis. Paradoxical reactions are reportedly found in approximately 5-10% of patients using anti-TNF-α agents and are no longer rare. Now that the use of biologics is at its culmination, reports regarding paradoxical reactions are predicted to increase in number; thus, we must recognize skin lesions with IBD patients including this type of adverse events and manage them appropriately while consulting with dermatologists.

DOI PubMed

Durable response after cessation of anti-programmed death 1 therapy in four melanoma patients.

Toshiya Handa, Junji Kato, Yasuyuki Sumikawa, Tokimasa Hida, Kohei Horimoto, Sayuri Sato, Masahide Sawada, Mao Fujioka, Tomoyuki Minowa, Yoshiyuki Matsui, Hisashi Uhara

The Journal of dermatology   46 ( 12 ) e461-e462 - e462  2019.12  [Refereed]  [International journal]

DOI PubMed

Adjuvant therapy with nivolumab versus ipilimumab after complete resection of stage III/IV melanoma: Japanese subgroup analysis from the phase 3 CheckMate 238 study.

Kenji Yokota, Hiroshi Uchi, Hisashi Uhara, Shusuke Yoshikawa, Tatsuya Takenouchi, Takashi Inozume, Kentaro Ozawa, Hironobu Ihn, Yasuhiro Fujisawa, Anila Qureshi, Veerle de Pril, Yasushi Otsuka, Jeffrey Weber, Naoya Yamazaki

The Journal of dermatology   46 ( 12 ) 1197 - 1201  2019.12  [Refereed]  [International journal]

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The multinational phase 3 CheckMate 238 trial compared adjuvant therapy with nivolumab versus ipilimumab among patients with resected stage III or IV melanoma (N = 906). In this Japanese subgroup analysis of CheckMate 238 (n = 28; nivolumab, n = 18; ipilimumab, n = 10), both the 12- and 18-month recurrence-free survival rates were 56% for nivolumab and 30% for ipilimumab (hazard ratio, 0.66; 97.56% confidence interval, 0.19-2.24; P = 0.4390). No new safety signals were reported for Japanese patients. Results were consistent with those from the CheckMate 238 global population, indicating that nivolumab has the potential to be a treatment option for Japanese patients with resected melanoma who are at high risk of recurrence.

DOI PubMed

Eosinophilic fasciitis in a 2-year-old child treated with a combination of methotrexate and corticosteroids.

Yuji Kan, Hisashi Uhara, Shiori Kamiya, Ayako Kumagai, Toshiya Handa

The Journal of dermatology   46 ( 12 ) e474-e475  2019.12  [International journal]

DOI PubMed

Japanese real-world study of sequential nivolumab and ipilimumab treament in melanoma.

Arata Tsutsumida, Satoshi Fukushima, Kenji Yokota, Shusuke Yoshikawa, Osamu Yamasaki, Atsushi Tanemura, Ryuhei Okuyama, Hisashi Uhara, Yusuke Muto, Azusa Miyashita, Masashi Akiyama, Tatsuya Kaji, Hiroshi Koga, Junji Kato, Teruaki Katayama, Eijun Itakura, Naoya Yamazaki, Yoshio Kiyohara

The Journal of dermatology   46 ( 11 ) 947 - 955  2019.11  [Refereed]  [International journal]

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To describe the treatment patterns of nivolumab and ipilimumab in Japan, a retrospective observational study was conducted in melanoma patients who received nivolumab and ipilimumab sequentially. Patients who received nivolumab and ipilimumab in combination were excluded from this study. Efficacy was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) in terms of the overall response rate (ORR), progression-free survival (PFS), and disease control rate (DCR). Overall survival (OS) was also evaluated. Safety was assessed by the Common Terminology Criteria for Adverse Events (CTCAE). The treatment for all 68 patients enrolled involved switching from nivolumab to ipilimumab in 61 patients and switching from ipilimumab to nivolumab in seven patients. Switching occurred because of progressive disease in 55 patients and adverse events in eight patients. The median number of ipilimumab doses was three. Ipilimumab treatment achieved an ORR and DCR of 4.9% and 21.3%, respectively, and the median OS from start of ipilimumab was 7.0 months. During the study period, no new safety signals were noted. Independent factors which were indicative of poor prognosis for PFS were high neutrophil-to-lymphocyte ratio (NLR) and high C-reactive protein (CRP) levels before ipilimumab treatment. An evaluation over a washout period indicated that no significant relationship existed with efficacy or safety. For the sequential administration of nivolumab and ipilimumab in Japanese melanoma patients, switch from nivolumab to ipilimumab was common, and the major reason for switching was progressive disease. The major prognostic factors for ipilimumab PFS after nivolumab were NLR and CRP before ipilimumab treatment.

DOI PubMed

肘に全周性に発症した熱傷瘢痕癌の1例

西田 彩華, 堀本 浩平, 執行 延明, 半田 稔也, 菅野 莉英, 松井 馨之, 藤岡 茉生, 大橋 隆宏, 加藤 潤史, 肥田 時征, 宇原 久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  129 ( 11 ) 2336 - 2336  2019.10