論文 - 舩越　建

Evaluation of the appropriate surgical margin for pigmented basal cell carcinoma according to the risk factors for recurrence: a single-institute retrospective study in Japan

Nakamura, Y. Tanese, K. Hirai, I. Kameyama, K. Kawakami, Y. Amagai, M. Funakoshi, T.

J Eur Acad Dermatol Venereol 32 （ 12 ） e453 - e455 2018年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0926-9959

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FRI-4 carbapenemase-producing Enterobacter cloacae complex isolated in Tokyo, Japan

Kubota H., Uwamino Y., Matsui M., Sekizuka T., Suzuki Y., Okuno R., Uchitani Y., Ariyoshi T., Aoki W., Suzuki S., Kuroda M., Shinkai T., Yokoyama K., Sadamasu K., Funakoshi T., Murata M., Hasegawa N., Iwata S.

Journal of Antimicrobial Chemotherapy （Journal of Antimicrobial Chemotherapy）  73 （ 11 ） 2969 - 2972 2018年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0305-7453

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© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Objectives: A carbapenem-resistant Enterobacter cloacae complex isolated in Tokyo, Japan, produced a carbapenemase that was detected by a Carba NP test and a modified carbapenem inactivation method, but none of the ‘Big Five’ carbapenemase genes was detected by PCR. This study aimed to identify the carbapenemase. Methods: Carbapenemase genes were screened by WGS. Next, we generated a recombinant plasmid in which the carbapenemase gene was inserted. We also extracted the carbapenemase gene-carrying plasmid from the E. cloacae complex. The effects of both plasmids on the antibiotic susceptibility of Escherichia coli were then tested. The carbapenemase gene-carrying plasmid in the E. cloacae complex was completely sequenced. Results: A novel carbapenemase gene, bla FRI-4 , encoded an amino acid sequence that was 93.2% identical to French imipenemase (FRI-1). E. coli transformed with bla FRI-4 showed reduced carbapenem susceptibility. A complete sequence of the bla FRI-4 -carrying 98 508 bp IncFII/IncR plasmid (pTMTA61661) showed that bla FRI-4 and the surrounding region (18.7 kb) were duplicated. Conclusions: The FRI-4-producing E. cloacae complex was isolated in Japan, whereas all other FRI variants have been found in Europe, suggesting that the spread of FRI carbapenemases is global.

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【血液疾患と皮膚病】臨床例　皮膚T細胞性リンパ腫　臨床経過と検査所見が非特異的で診断に苦慮した例

齋藤 苑子, 栗原 佑一, 平井 郁子, 中村 善雄, 海老原 全, 舩越 建

皮膚病診療 （(株)協和企画）  40 （ 11 ） 1131 - 1134 2018年11月

ISSN  0387-7531

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＜文献概要＞症例のポイント　・四肢・体幹に紅斑や丘疹,結節のほか,腫瘤を認める臨床像でありながら,病理組織学的に小型の異型の乏しいリンパ球浸潤であり,古典的菌状息肉症の腫瘤期としては非特異的であり,診断に苦慮した皮膚T細胞性リンパ腫(cutaneous T-cell lymphoma:CTCL)の1例を経験した.・ステロイド外用療法,光線療法で治療を開始したが改善に乏しく,ベキサロテン内服治療により皮疹の改善を認めた.

皮膚T細胞リンパ腫　臨床経過と検査所見が非特異的で診断に苦慮した例

齋藤苑子, 栗原佑一, 平井郁子, 中村善雄, 海老原全, 舩越建

皮膚病診療 40 （ 11 ） 1131 - 1134 2018年11月

共著, 査読有り

Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma

Fujimura T, Sato Y, Tanita K, Kambayashi Y, Otsuka A, Fujisawa Y, Yoshino K, Matsushita S, Funakoshi T, Hata H, Yamamoto Y, Uchi H, Nonomura Y, Tanaka R, Aoki M, Imafuku K, Okuhira H, Wada N, Irie H, Hidaka T, Hashimoto A, Aiba S

Front Oncol 8   530 2018年11月

共著, 査読有り,  ISSN  2234-943X

Azathioprine-induced alopecia and leukopenia associated with NUDT15 polymorphisms

Nomura H, Kurihara Y, Saito M, Fukushima A, Shintani Y, Shiiyama R, Toshima S, Kamata A, Yamagami J, Funakoshi T, Kameyama K, Amagai M, Kubo A, Umegaki-Arao N

Journal of the European Academy of Dermatology and Venereology （Journal of the European Academy of Dermatology and Venereology）  32 （ 10 ） e386 - e389 2018年10月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0926-9959

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Baseline neutrophil to lymphocyte ratio combined with serum lactate dehydrogenase level associated with outcome of nivolumab immunotherapy in a Japanese advanced melanoma population.

Fujisawa, Y. Yoshino, K. Otsuka, A. Funakoshi, T. Fujimura, T. Yamamoto, Y. Hata, H. Tanaka, R. Yamaguchi, K. Nonomura, Y. Hirai, I. Furudate, S. Okuhira, H. Imafuku, K. Aoki, M. Matsushita, S.

Br J Dermatol 179 （ 1 ） 213 - 215 2018年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0007-0963

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Carboplatin and epirubicin combination therapy for advanced malignant epithelial skin tumors: Retrospective study of six patients

Nakamura, Y. Tanese, K. Hirai, I. Kawakami, Y. Funakoshi, T.

J Dermatol 45 （ 7 ） 874 - 875 2018年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0385-2407

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Vancomycin Mediates IgA Autoreactivity in Drug-Induced Linear IgA Bullous Dermatosis

Yamagami J., Nakamura Y., Nagao K., Funakoshi T., Takahashi H., Tanikawa A., Hachiya T., Yamamoto T., Ishida-Yamamoto A., Tanaka T., Fujimoto N., Nishigori C., Yoshida T., Ishii N., Hashimoto T., Amagai M.

Journal of Investigative Dermatology （Journal of Investigative Dermatology）  138 （ 7 ） 1473 - 1480 2018年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0022-202X

　概要を見る

© 2018 The Authors Vancomycin (VCM) is known to induce linear IgA bullous dermatosis (LAD). However, in contrast to conventional LAD, in which circulating IgA autoantibodies against basement membrane proteins are commonly detected, patient sera from VCM-induced LAD yields negative results in indirect immunofluorescence microscopy, and the targeted autoantigen remains undetermined. By using sera from a typical patient with VCM-induced LAD, we identified that co-incubation of sera with VCM resulted in linear IgA deposition at the basement membrane zone by indirect immunofluorescence. Patient sera reacted with the dermal side of 1 mol/L NaCl-split skin and with the recombinant noncollagenous (i.e., NC1) domain of type VII collagen by both immunoblot and ELISA in the presence of VCM. The investigation of an additional 13 patients with VCM-induced LAD showed that 10 out of the 14 sera (71.4%) reacted with the NC1 domain of type VII collagen by ELISA when spiked with VCM, whereas only 4 (28.6%) tested positive without it. The enhancement of reactivity to NC1 by VCM, as determined by optical density via ELISA, was observed in 10 out of the 14 sera (71.4%). These findings indicate that type VII collagen is a target autoantigen in VCM-induced LAD and that VCM mediates IgA autoreactivity against type VII collagen, providing an insight into mechanisms involved in drug-induced autoimmune disease.

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Combination of low-dose total skin electron beam therapy and subsequent localized skin electron beam therapy as a therapeutic option for advanced-stage mycosis fungoides

Kinoshita-Ise M., Ouchi T., Izumi E., Kawaguchi O., Nagao K., Amagai M., Funakoshi T.

Clinical and Experimental Dermatology （Clinical and Experimental Dermatology）  43 （ 4 ） 437 - 440 2018年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0307-6938

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© 2017 British Association of Dermatologists Electron beam therapy (EBT) is an established treatment for mycosis fungoides (MF), but evidence for the use of EBT in advanced cutaneous conditions is limited, and optimal scheduling of the regimen for such conditions remains unclear. We report the case of a 44-year-old woman diagnosed with MF with widespread cutaneous lesions, including multiple huge tumours in the craniofacial area. Low-dose total skin (TS)EBT and subsequent localized skin (LS)EBT achieved striking improvements in eruptions. Oral etretinate was also administered during therapy. Our experience implies that combined TSEBT and LSEBT may be worth attempting when a patient presents with both widespread lesions and prominent tumours, even when the tumours are extremely large.

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Case of lamotrigine-induced drug adverse reaction under tocilizumab treatment with clinical and virological features of drug-induced hypersensitivity syndrome

Iriki H., Ouchi T., Ito H., Sawada M., Mukai M., Nomura H., Baba Y., Adachi T., Funakoshi T., Amagai M., Takahashi H.

Journal of Dermatology （Journal of Dermatology）  45 （ 6 ） 738 - 741 2018年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0385-2407

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© 2018 Japanese Dermatological Association The pathological mechanisms and immunological kinetics of drug-induced hypersensitivity syndrome (DIHS), including the relevance of interleukin (IL)-6, remain unclear. We report a case of drug adverse reaction that does not fulfill the diagnostic criteria of DIHS but mimics its characteristic features. Because the patient was under anti-IL-6 therapy at the onset, some symptoms typically seen in DIHS were absent, such as fever and leukocyte count abnormalities. However, the characteristic features of DIHS were clearly observed in the subsequent course, including the repeated recurrence of skin rash, prolonged liver dysfunction and reactivation of herpes viruses. This case suggested that IL-6 role at the onset is not a main factor to determine the subsequent pathomechanism of DIHS and attention should be paid to the preceding therapy for achieving accurate diagnosis.

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Unique clinical and serological features of bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors

Horikawa H, Kurihara Y, Funakoshi T, Umegaki-Arao N, Takahashi H, Kubo A, Tanikawa A, Kodani N, Minami Y, Meguro S, Itoh H, Izumi K, Nishie W, Shimizu H, Amagai M, Yamagami J

Br J Dermatol 178 （ 6 ） 1462 - 1463 2018年06月

共著, 査読有り,  ISSN  0007-0963

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Assessment of the methods used to detect HER2-positive advanced extramammary Paget’s disease

Hirai I., Tanese K., Nakamura Y., Otsuka A., Fujisawa Y., Yamamoto Y., Hata H., Fujimura T., Matsushita S., Yoshino K., Kameyama K., Amagai M., Funakoshi T.

Medical Oncology （Medical Oncology）  35 （ 6 ） 92 2018年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1357-0560

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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The human epidermal growth factor receptor 2 (HER2) is recognized as an oncogene as well as a therapeutic target in various cancers. Certain patients with advanced extramammary Paget’s disease (EMPD) have also been reported to express HER2, which is therefore considered a therapeutic target for EMPD. However, an accurate methodology to determine HER2-positive EMPD has not been established. To assess the optimal methods for detection of HER2-positive EMPD, 73 EMPD samples were analyzed by immunohistochemical (IHC) staining, fluorescence in situ hybridization (FISH), and the HER2 testing algorithm for breast cancer of the American Society of Clinical Oncology/College of American Pathologists, which combined the results of IHC staining and FISH. The results showed discordance in the rate of positive IHC staining and FISH results. While 68.6% (24/35) of the metastatic samples showed equivocal or positive IHC staining, only 37.1% (13/35) were positive by FISH. To assess the accuracy of these methods, the degree of HER2 expression detected by each method was correlated with the staining profiles of activated downstream signaling pathways involving phosphorylated p44/42 MAPK (Thr202/Tyr204) (p-ERK1/2) and phosphorylated AKT (Ser473) (p-AKT). Among 16 lymph node metastasis samples, all HER2-positive samples as determined by the testing algorithm stained positively for both p-ERK1/2 and p-AKT. On the other hand, 10-14.3% of the samples determined by FISH or IHC showed negative staining for p-ERK1/2 and p-AKT. The results showed that combining the results of IHC and FISH according to the HER2 testing algorithm is a useful method for accurately evaluating HER2-positive EMPD.

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女性化乳房様を呈し，皮膚悪性腫瘍を疑った嚢胞内乳癌の男性例

八谷美穂, 梅垣知子, 江原佳恵, 舩越建, 高橋麻衣子, 天谷雅行

皮膚科の臨床 （金原出版(株)）  60 （ 5 ） 726 - 727 2018年05月

共著, 査読有り,  ISSN  0018-1404

　概要を見る

65歳男性。右乳房腫瘤を主訴とした。2年前から右乳房が腫脹し、徐々に増大した。右乳房に12cm大の表面平滑な嚢胞性腫瘤を認め、腫瘤により皮膚が伸展し、菲薄化していた。皮膚悪性腫瘍を疑い、生検を行った。病理組織学的所見では、乳頭直下に嚢胞性病変を認め、真皮内には腫瘍細胞が増殖し、腺管状構造を伴っていた。免疫染色はER陽性、PgR陽性であった。乳癌を疑い、PET-CTを施行した。右乳腺に59×23mm大の高度に集積亢進する嚢胞性腫瘤と、右腋窩に9×5mm大の集積亢進を伴ったリンパ節腫脹を認めた。右乳腺の針生検で腺管構造を伴う異型細胞の増殖を認め、腺管は筋上皮と上皮の二相性を欠いていた。乳腺癌の所見であったが、明らかな間質浸潤はみられなかった。嚢胞内乳癌を疑い、右胸筋温存乳房切除術および右腋窩リンパ節郭清術を施行した。切除検体で間質への浸潤を認め、浸潤性乳管癌と診断された。

血気胸を伴う多発肺転移を合併した頭部血管肉腫の1例

平田佳子, 平井郁子, 栗原佑一, 高田圭以子, 大原博敏, 神山育男, 天谷雅行, 舩越建

臨床皮膚科 （(株)医学書院）  72 （ 4 ） 341 - 345 2018年04月

共著, 査読有り,  ISSN  0021-4973

　概要を見る

＜文献概要＞86歳,男性.初診4ヵ月前に右側頭部の有痛性の結節を自覚した.近医にて炎症性粉瘤の疑いで切開後,創部が改善せず,潰瘍が拡大した.初診1ヵ月前に両側気胸が発症し,CTで頭部血管肉腫肺転移を疑われ,両側胸腔ドレーンを留置後,当科へ転院した.頭部の潰瘍の生検病理組織像で血管肉腫と診断後,電子線照射を開始した.肺病変は胸腔ドレーン抜去後に全身化学療法を始める方針とした.しかし,血胸水の増悪と気胸の再発を認め,左肺嚢胞結紮術と両側胸膜癒着術を行ったが,病勢が進行し,入院41日目に呼吸不全で永眠された.頭部血管肉腫肺転移による血気胸は再発性・難治性であり,気胸発症後の平均生存期間は4.1ヵ月と予後不良である.過去の胸腔ドレーン適応例では,胸膜癒着術や外科的治療中に転移巣が進行し,再発する例が多かった.近年,胸腔内化学療法の気胸改善や病勢制御への有用性が報告されており,進行例での適応を積極的に検討すべきと考えた.

Azathioprine monotherapy in autoimmune blistering diseases: A feasible option for mild to moderate cases

Kakuta R., Yamagami J., Funakoshi T., Takahashi H., Ohyama M., Amagai M.

Journal of Dermatology （Journal of Dermatology）  45 （ 3 ） 334 - 339 2018年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0385-2407

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© 2017 Japanese Dermatological Association Azathioprine (AZP) is used as a corticosteroid (CS)-sparing medication to treat autoimmune blistering diseases. In this study, we examined the efficacy of AZP and the feasibility of using AZP monotherapy (without CS) to treat pemphigus and pemphigoid. We performed a retrospective study of 10 Japanese patients (seven with pemphigus and three with pemphigoid) with mild to moderate disease activity who had been treated using AZP. The treatment efficacy was evaluated based on decreases in the disease activity scores and autoantibody titers. The results demonstrate that seven out of 10 cases (70%) were treated successfully using AZP monotherapy with no severe adverse effects. The disease activity scores of the successfully-treated patients decreased to zero after 1–37.5 months (average, 11.9) and the average disease activity scores in these cases decreased significantly at 2 months (38.2 ± 36.6%) compared with the scores of the three patients who required additional systemic CS therapy (77.5 ± 3.5%) (P < 0.05). Additionally, the autoantibody titers of five cases treated successfully using AZP decreased by half at 6 months. In conclusion, our findings suggest that AZP monotherapy is a viable treatment option for mild to moderate pemphigus and pemphigoid.

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Multifocal primary melanoma of the cervical spinal cord successfully treated by tumorectomy: a case report

Iga, T. Iwanami, A. Funakoshi, T. Mikami, S. Tsuji, O. Nagoshi, N. Okada, E. Fujita, N. Yagi, M. Watanabe, K. Nakamura, M. Matsumoto, M.

Spinal Cord Ser Cases 4   24 2018年03月

共著, 査読有り,  ISSN  2058-6124

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Metastatic Extramammary Paget's Disease: Pathogenesis and Novel Therapeutic Approach

Fukuda, K. Funakoshi, T.

Front Oncol 8 （ 38 ） 1 - 8 2018年02月

研究論文（学術雑誌）, 共著, 査読有り

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Serum levels of soluble CD163 and CXCL5 may be predictive markers for immune-related adverse events in patients with advanced melanoma treated with nivolumab: A pilot study

Fujimura T., Sato Y., Tanita K., Kambayashi Y., Otsuka A., Fujisawa Y., Yoshino K., Matsushita S., Funakoshi T., Hata H., Yamamoto Y., Uchi H., Nonomura Y., Tanaka R., Aoki M., Imafuku K., Okuhira H., Furudate S., Hidaka T., Aiba S.

Oncotarget （Oncotarget）  9 （ 21 ） 15542 - 15551 2018年02月

共著, 査読有り,  ISSN  1949-2553

　概要を見る

© Fujimura et al. Antibodies against PD-1, such as nivolumab and pembrolizumab, are widely used in the treatment of various cancers including advanced melanoma. The anti- PD-1 Ab significantly prolongs survival in patients with metastatic melanoma, and its administration in combination with local or systemic therapy may also lead to improved outcomes. Although anti-PD-1 Ab-based combined therapy might be effective for the treatment of advanced melanoma, the associated risk of irAEs is an important consideration. Therefore, being able to predict irAEs is of great interest to oncologists. The purpose of this study was to evaluate the value of using serum levels of sCD163 and CXCL5 to predict irAEs in patients with advanced melanoma who were administered nivolumab. To this end, we analyzed these serum levels in 46 cases of advanced melanoma treated with nivolumab. In addition, the tumor stroma was evaluated by immunohistochemistry and immunofluorescence. We measured the serum levels of sCD163 and CXCL5 on day 0 (immediately before nivolumab administration) and day 42. The serum absolute levels of sCD163 were significantly increased in patients who developed AEs (p = 0.0018). Although there was no significant difference in serum levels of CXCL5, the absolute value of CXCL5 could at least be a supportive marker for the increased absolute levels of serum sCD163. This study suggests that sCD163 and CXCL5 may serve as possible prognostic biomarkers for irAEs in patients with advanced melanoma treated with nivolumab.

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タンポンの使用に起因したToxic shock syndromeの1例

椎山理恵 持丸奈央子 舩越 建 大山宗徳 菅井基行 天谷雅行

皮膚病診療 40 （ 2 ） 193 - 196 2018年02月

査読有り