Faculty Profiles - YANAI Hiroyuki

Papers - YANAI Hiroyuki

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Biphenotypic sinonasal sarcomaの1例 Reviewed

林詠子, 祇園由佳, 藤澤真義, 能島舞, 田中顕之, 田中健大, 柳井広之, 吉野正

診断病理 34 ( 4 ) 293 - 298 2017.10

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本病理学会

患者は50代女性。半年前から徐々に増悪する右鼻閉を訴えていた。画像検査にて頭蓋底に浸潤する右鼻腔・右篩骨洞腫瘤を指摘され、摘出術が施行された。組織学的に上皮下に紡錐形核を有する均一な細胞が束状に増殖しており、staghorn patternを示す血管がみられた。細胞異型や核分裂像に乏しく、壊死はみられなかった。免疫組織化学的に紡錐形細胞はS100蛋白(+)、α-smooth muscle actin(+)、Ki-67陽性率は1%以下であった。電子顕微鏡にて細胞質内にfocal dense plaqueを、RT-PCRにてPAX3-FOXO1融合遺伝子産物が認められた。以上より近年sinonasal tractに発生する新しい腫瘍の一つとして提唱された、biphenotypic sinonasal sarcomaと診断した。(著者抄録)

増大する皮下腫瘤を呈した結核性胸壁膿瘍の一例

三好智子, 草野展周, 久保寿夫, 大重和樹, 江原弘貴, 頼冠名, 柳井広之, 大塚文男

日本病院総合診療医学会雑誌 13 ( 2 ) 27 - 28 2017.9

Language：Japanese Publisher：(一社)日本病院総合診療医学会

74歳男。右肋弓部の増大する皮下腫瘤を主訴とした。右第12肋骨下極に皮下腫瘤を触知し、腹部超音波検査では内部不均一な腫瘤を認め、MRI・CTでは右下位肋軟骨骨折を伴う胸腔側と胸壁外にまたがる膿瘍様の病変を認めた。胸部CTでは胸膜石灰化を認めるのみであった。既往歴に2型糖尿病があるものの血糖コントロールは良好で、クォンティフェロンは陽性、膿瘍穿刺液中の抗酸菌塗抹検査では結核菌は検出しなかったが、小切開にて摘出した膿瘍の抗酸菌塗抹検査および培養では結核菌を認め、結核菌による胸壁膿瘍と診断した。病理検査では乾酪壊死を伴った類上皮肉芽腫であった。胸壁膿瘍に対し、抗結核薬内服治療開始となった。

Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue with Plasma Cell Differentiation: Periodic Acid-Schiff Reaction-Positive Dutcher Body is a Diagnostic Clue to Distinguish it from Plasmacytoma Reviewed

Atsuko Nasu, Takuro Igawa, Hiaki Sato, Hiroyuki Yanai, Tadashi Yoshino, Yasuharu Sato

DIAGNOSTIC CYTOPATHOLOGY 45 ( 6 ) 547 - 551 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

We herein report a case of primary parotid extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with Dutcher bodies. An 82-year-old man presented with a 4 cm x 2.5 cm mass in the left parotid region. Positron emission tomography/computed tomography (PET/CT) showed localized abnormal fluorodeoxyglucose (FDG) uptake in the left parotid gland and lymph nodes of the left cervical region. Fine needle aspiration (FNA) cytology of the left parotid gland showed lymphoplasmacytoid cells with periodic acid-Schiff (PAS)-positive Dutcher bodies. A subsequent excisional biopsy showed sheets of small- to medium-sized neoplastic B cells with abundant IgM in the cytoplasm as detected by immunohistochemistry. A diagnosis of stage II MALT lymphoma was made, but the patient did not receive therapeutic intervention. As previously reported, Dutcher bodies are mainly observed in B-cell neoplasms with IgM production. Because these characteristic intranuclear inclusions can be easily observed by PAS staining, the presence of PAS reaction-positive Dutcher bodies in FNA cytology can serve as a clue to differentially diagnose MALT lymphoma from plasmacytoma. (C). 2017 Wiley Periodicals, Inc.

DOI： 10.1002/dc.23691

ラブドイド細胞を主体とした耳下腺筋上皮癌の1例

那須篤子, 畠榮, 藤田勝, 濱田香菜, 今井みどり, 田中健大, 柳井広之

日本臨床細胞学会雑誌 56 ( 3 ) 137 - 142 2017.5

Language：Japanese Publisher：(公社)日本臨床細胞学会

背景:耳下腺に発生したラブドイド細胞を主体とした筋上皮癌の1例を経験したので細胞所見を中心に報告する。症例:60歳代、男性。左耳前部腫瘤を主訴として近医を受診後、当院を紹介受診。CTにて左耳前部に内部壊死様で辺縁不整を示す腫瘤影を認めた。耳下腺穿刺吸引細胞診では、壊死物質を背景にライトグリーン好性の豊富な細胞質と偏在核を有するラブドイド細胞が散在性あるいは小集塊状に出現していた。悪性を除外しえないため、耳下腺腫瘍摘出術ならびにリンパ節郭清術が施行された。組織所見および免疫組織化学的所見より筋上皮癌と診断した。結論:唾液腺腫瘍の細胞診において、ラブドイド細胞を認めた場合には、まれではあるが筋上皮癌も念頭におき検索する必要があると考えられた。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01209&link_issn=&doc_id=20170915320003&doc_link_id=%2Few5saibo%2F2017%2F005603%2F004%2F0137-0142%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Few5saibo%2F2017%2F005603%2F004%2F0137-0142%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Verification of Implant Surface Modification by a Novel Processing Method Reviewed

Yoshiki Okada, Nobuhiro Abe, Noriyuki Hisamori, Toshiaki Kaneeda, Shigeaki Moriyama, Hitoshi Ohmori, Masayoshi Mizutani, Hiroyuki Yanai, Yoshio Nakashima, Yusuke Yokoyama, Toshifumi Ozaki

ACTA MEDICA OKAYAMA 71 ( 1 ) 49 - 57 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

Metals have been used clinically as biomaterials, especially in the orthopaedic and dental fields. Metals used as implants wear at contact surfaces, producing metal particles and metal ions that may be harmful. Newly developed metal implants and methods of implant surface modification are currently under scrutiny. We evaluated the use of electrolytic in-process dressing (ELID) as a surface finishing method for metal implants. Metal implants processed using the ELID method (ELID group) or not processed (Non-ELID group) were inserted surgically into rabbit femurs. The rabbits were sacrificed postoperatively over a 24-week period. We assessed the concentrations of the cytokines, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-a, the resistance to implant pull-out, and histopathology at the implant site. There was no significant difference between the groups regarding the cytokine concentrations or implant pull-out resistance. Many particles indicating wear around the implant were noted in the Non-ELID group (n=10) but not the ELID group (n=13), while a fibrous membrane adhering to the every implant was noted in the ELID group. The formation of a fibrous membrane rather than metal particles in the ELID group may indicate improved biocompatibility, and it suggests that ELID may prevent corrosion in the areas of contact.

Trastuzumab Emtansine in HER2+Recurrent Metastatic Non-Small-Cell Lung Cancer: Study Protocol Reviewed

Kadoaki Ohashi, Katsuyuki Hotta, Taizo Hirata, Keisuke Aoe, Toshiyuki Kozuki, Kiichiro Ninomiya, Hiroe Kayatani, Hiroyuki Yanai, Shinichi Toyooka, Shiro Hinotsu, Minoru Takata, Katsuyuki Kiura

CLINICAL LUNG CANCER 18 ( 1 ) 92 - 95 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：CIG MEDIA GROUP, LP

The treatment outcome has been unsatisfactory for patients with non small-cell lung cancer (NSCLC) refractory to standard first-line chemotherapy. Trastuzumab emtansine (T-DM1), an anti-HER2 antibody conjugated with a vinca alkaloid, has been approved for clinical use in HER2+ breast cancer in many countries. Approximately 5% of NSCLC tumors possess HER2 alterations, and T-DM1 has shown excellent antitumor effects against HER2+ lung cancer cell lines in preclinical models. Therefore, we hypothesized that T-DM1 could significantly inhibit the growth of HER2+ lung cancers. We have launched a nonrandomized phase II trial of T-DM1 monotherapy for patientg with HER2+ lung cancers. The major eligibility criteria are as follows: age >= 20 years, pathologically diagnosed NSCLC with documented HER2 positivity (immunohistochemistry 3+, both immunohistochemistry 2+ and fluorescence in situ hybridization positive, or exon 20 insertion mutation), and previous chemotherapy. Thirty patients will receive T-DM1 3.6 mg/kg every 3 weeks. The primary endpoint is the overall response rate. This trial will provide information on whether T-DM1 monotherapy is effective against HER2+ lung cancer. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cllc.2016.06.014

Comparative study on driver mutations in primary and metastatic melanomas at a single Japanese institute: A clue for intra- and inter-tumor heterogeneity Reviewed

Tatsuya Kaji, Osamu Yamasaki, Minoru Takata, Masaki Otsuka, Toshihisa Hamada, Shin Morizane, Kenji Asagoe, Hiroyuki Yanai, Yoji Hirai, Hiroshi Umemura, Keiji Iwatsuki

JOURNAL OF DERMATOLOGICAL SCIENCE 85 ( 1 ) 51 - 57 2017.1

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Background: Searching for driver mutations in melanoma is critical to understanding melanoma genesis, progression and response to therapy.
Objectives: We aimed to investigate the frequency and pattern of driver mutations in Japanese primary and metastatic melanomas including cases of unknown primary origin, in relation to their clinicopathologic manifestations.
Methods: Seventy-seven samples from 60 patients with melanoma were screened for 70 driver mutations of 20 oncogenes by Sequenom MelaCarta MassARRAY, and the results for primary and metastatic melanomas were compared.
Results: Of 77 tissue samples, BRAFV60 OE was detected in 21 samples (27%), CDK4 R24C in 7, EPHB6 G404S in 6, BRAF V600 K in 2, NEK10 E379 K in 2, and CDK4 R24H, NRAS Q61 K, NRAS Q61R, KRAS GI2A, KIT L576P, KIT V559A, ERBB4 E452 K, and PDGFRA E996 K in one sample each. No driver mutations related to the MAPK cascade including MS and BRAF were detected in the chronically sun-damaged (CSD) group of melanoma. Dual or triple driver mutations were found in four of 40 (10%) samples from the primary melanomas, and three of 37 (8%) of the metastatic melanomas. Fourteen of 26 (54%) samples of non-CSD melanoma, and 3 of 6 (50%) melanomas of unknown primary origin had the BRAF V600E mutation. Mutations in membrane-bound receptors including KIT, ERBB4 and EPHB6 were detected in 8 of 77 (10%) samples. Of 17 pairs of primary and metastatic melanomas from the same patient, the primary mutation pattern was changed to a novel one in three cases, and only one of the plural mutations in the primary melanoma was found in the metastatic lesions in two cases.
Conclusions: BRAF V600E is a predominant mutation in non-CSD melanoma and melanomas of unknown primary origin. Mutational heterogeneity may exist in the primary melanoma (intra-tumor heterogeneity), and between the primary and metastatic lesions (inter-tumor heterogeneity). (C) 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.jdermsci.2016.10.006

治療に難渋した壊死性好酸球性心筋炎の１例

小出祐嗣, 中村一文, 木村朋生, 中川晃志, 三好亨, 西井伸洋, 伊藤浩, 大澤晋, 笠原慎吾, 田中健大, 柳井広之, 安藤翠, 大郷恵子, 山中俊明

心臓 49 ( Suppl.1 ) 159 - 167 2017

Language：Japanese Publisher：(公財)日本心臓財団

症例は16歳男性。血圧低下をきたし前医搬送。冠動脈造影・左室造影・心筋生検を施行。好酸球性心筋炎と診断し3日間メチルプレドニゾロン(m-PSL)1g/日投与。その後PSLを減量するも好酸球数再増加を伴う血行動態悪化を認め、計3度のmPSL大量投与、γ-glb大量療法およびアザチオプリン投与を併用することで好酸球増多は認めなくなり心筋炎は改善した。その後PSL漸減可能となった。第27病日、感染契機に頻脈、血圧低下しPCPS挿入。第29病日PCPS挿入側の右下肢腫脹を認め減張切開施行。第45病日右下肢壊疽に対して右大腿切断術施行。第57病日小腸穿孔による急性汎発性腹膜炎をきたたし緊急手術を施行し小腸切除、ストーマ造設。その後感染コントロールが付いた後にPSLを漸減。PSL 5mgまで減量し、第188日ストーマ閉鎖。第211病日、リハビリ目的に前医転院となった。その後復学し現在外来通院中。ステロイド単剤では治療に難渋したが、アザチオプリンを追加投与することで治療し得た。(著者抄録)

乳児Atypical teratoid/rhabdid tumorに対する放射線治療および分子生物学的分類と予後との関連について.

大谷理浩, 市川智継, 黒住和彦, 安原隆雄, 鷲尾佳奈, 嶋田明, 片山敬久, 勝井邦彰, 柳井広之, 伊達勲

脳神経外科 45 ( 2 ) 147 - 154 2017

A case of Alpha-Fetoprotein producing hepatoid adenocarcinoma of the uterine corpus

35 ( 1 ) 35 - 42 2017

[Prognostic Impact of Radiation Therapy and Molecular Classification of Infant Atypical Teratoid/Rhabdoid Tumors]. Reviewed

Yoshihiro Otani, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Takao Yasuhara, Kana Washio, Akira Shimada, Norihisa Katayama, Kuniaki Katsui, Hiroyuki Yanai, Isao Date

No shinkei geka. Neurological surgery 45 ( 2 ) 147 - 154 2017

Language：English Publishing type：Research paper (scientific journal)

Atypical teratoid/rhabdoid tumor(AT/RT)is a rare and lethal childhood cancer. Although radiation therapy in children less than three years of age is generally deferred because of its neural toxicity, recent studies have shown that multimodal therapies, including radiation therapy, are effective in pediatric patients with AT/RT less than three years of age. We treated four infant AT/RT patients and investigated the impact of radiation therapy and genetic classification on the prognosis. The mean age at the time of the operation was 9.3 months and all patients were female. All patients underwent surgical resection. Of the four patients, two received combined irradiation and chemotherapy. Specifically, one patient received conformal craniospinal radiation therapy and the other received craniospinal irradiation with proton beams. Immunohistochemical analyses of tumor specimens revealed that the two patients were positive for ASCL1, a regulator of Notch signaling. Patients who received radiation therapy and exhibited ASCL1-positive tumors had a better prognosis. We conclude that radiation therapy may prolong survival in AT/RT patients who are less than 3 years of age. However, further study is required to evaluate long-term functional outcomes.

DOI： 10.11477/mf.1436203466

前頭葉に発生し、てんかん原性を示した髄膜腫合併髄膜血管腫症の1例 Reviewed

河原明奈, 伏見聡一郎, 板倉淳哉, 藤澤真義, 小林勝弘, 林裕美子, 伊達勲, 上利崇, 柳井広之, 松川昭博

診断病理 34 ( 1 ) 46 - 50 2017

Language：Japanese Publisher：(一社)日本病理学会

17歳、男性。てんかん発作を幼少期より繰り返していた。3歳時の頭部CTでは病変を指摘されなかったが、13歳時に左中前頭回の脳表に石灰化を伴う病変を認めた。発作頻度が増したため、17歳時に病変とその直下のてんかん焦点を含む左前頭葉部分切除術が施行された。脳表側では砂粒体と渦巻き状に紡錘形細胞が認められ、移行性髄膜腫であった。大脳側では血管が網目状に増生し、血管周囲には髄膜皮細胞が取り巻く髄膜血管腫症であった。症状や画像の経過より髄膜血管腫症が先行し、その後髄膜腫が合併したと考えられた。(著者抄録)

Adenovirus vector carrying REICIDKK-3 gene: neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy Reviewed

H. Kumon, Y. Ariyoshi, K. Sasaki, T. Sadahira, M. Araki, S. Ebara, H. Yanai, M. Watanabe, Y. Nasu

CANCER GENE THERAPY 23 ( 11 ) 400 - 409 2016.11

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kaftan's nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. After confirming the safety of the therapeutic interventions with initially planned three escalating doses of 1.0 x 10(10), 1.0 x 10(11) and 1.0 x 10(12) viral particles (vp) in 1.0-1.2 ml (n=3, 3 and 6), an additional higher dose of 3.0 x 10(12) vp in 3.6 ml (n=6) Was further studied. All four DLs including the additional dose level-4 (DL-4) were feasible with no adverse events, except for grade 1 or 2 transient fever. Laboratory toxicities were grade 1 or 2 elevated aspartate transaminase/alanine transaminase (n=4). Regarding antitumor activities, cytopathic effects (tumor degeneration With cytolysis and pyknosis) and remarkable tumor-infiltrating lymphocytes in the targeted tumor areas were detected in a clear dose-dependent manner. Consequently, biochemical recurrence-free survival in DL-4 was significantly more favorable than in patient groups DL-1+2+2:

DOI： 10.1038/cgt.2016.53

CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine Reviewed

Nobuhiko Ohnishi, Katsuyoshi Takata, Tomoko Miyata-Takata, Yasuharu Sato, Akira Tari, Yuka Gion, Mai Noujima-Harada, Kohei Taniguchi, Tetsuya Tabata, Keina Nagakita, Shizuma Omote, Hiroyuki Takahata, Masaya Iwamuro, Hiroyuki Okada, Yoshinobu Maeda, Hiroyuki Yanai, Tadashi Yoshino

CANCER SCIENCE 107 ( 11 ) 1687 - 1695 2016.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Follicular lymphoma (FL) shows co-expression of B-cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa-associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10(down)) GI-FL. The diagnosis of CD10(down) FL was carried out with a combination of pathological and molecular analyses. The incidence of CD10(down) GI-FL was shown in 35/172 (20.3%) cases, which was more frequent than nodal FL (3.5%, P < 0.001). The difference was additionally significant between GI-FL and nodal FL when the analysis was confined to primary GI-FL (55.2% vs 3.5%, P < 0.001). Compared to CD10(+) GI-FL, CD10(down) GI-FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the downexpression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10(down) group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which indicated caution in the differentiation of mucosa-associated lymphoid tissue lymphoma. Molecular analyses were undertaken in seven cases of CD10(down) GI-FL, and an identical clone was found between CD10(down) follicles and CD10(+)BCL2(+) neoplastic follicles. In the diagnosis of cases with CD10(down) BCL2(+) follicles, careful examination with molecular studies should be carried out.

DOI： 10.1111/cas.13031

Histological spectrum of angiofibroma of soft tissue: histological and genetic analysis of 13 cases Reviewed

Yuichi Yamada, Hidetaka Yamamoto, Kenichi Kohashi, Takeaki Ishii, Kunio Iura, Akira Maekawa, Hirofumi Bekki, Hiroshi Otsuka, Kyoko Yamashita, Hiroyuki Tanaka, Tsubasa Hiraki, Munenori Mukai, Atsuko Shirakawa, Yoko Shinnou, Mari Jinno, Hiroyuki Yanai, Kenichi Taguchi, Yoshihiko Maehara, Yukihide Iwamoto, Yosinao Oda

HISTOPATHOLOGY 69 ( 3 ) 459 - 469 2016.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

AimsAngiofibroma of soft tissue (AFST) is a rare soft tissue neoplasm characterized by a fibroblastic cytomorphology and a prominent vascular structure. AFSTs possess a novel fusion gene, i.e. NCOA2-AHRR/AHRR-NCOA2 or GTF2I-NCOA2, providing a useful approach to diagnosing AFST. Morphologically, AFSTs span a wide spectrum, making diagnosis a challenge. The aim of this study was to review AFST cases and to report previously unknown histological features, which we confirmed by genetic analysis.
Methods and resultsWe reviewed 276 cases diagnosed as solitary fibrous tumours/haemangiopericytomas (232 cases), unclassified tumours of fibroblastic differentiation (36 cases), and recently diagnosed AFSTs (eight cases), and retrieved 13 cases compatible with AFST. Immunohistochemical staining was performed for these cases, all 13 of which were analysed by reverse transcription polymerase chain reaction and fluorescence in-situ hybridization. The histological findings were as follows: amianthoid fibres, extravasation of red blood cells, haemosiderin deposition, aggregates of foamy histiocytes, cystic change, necrosis, and haemorrhage. Immunohistochemically, the tumour cells were positive for epithelial membrane antigen (four of 13 cases), desmin (six of 13 cases), CD163 (13 of 13 cases), CD68 (seven of 13 cases), oestrogen receptor (13 of 13 cases), progesterone receptor (three of 13 cases), and STAT6 (one of 13 cases, weak nuclear staining), but they were negative for CD34, -smooth muscle actin, muscle-specific actin, S100, pan-cytokeratin, MDM2, and CDK4. The AHRR-NCOA2 fusion gene was detected in eight cases, and NCOA2 gene rearrangement in nine cases.
ConclusionWe revealed the previously unreported histological variation and immunohistochemical findings of AFST, and confirmed them by using genetic methods. The results suggested that AFST should be considered in the diagnosis of fibrous or fibrohistiocytic tumours with the above histological features.

DOI： 10.1111/his.12943

A Case of Focal Bone Marrow Reconversion Mimicking Bone Metastasis: The Value of (111)Indium Chloride Reviewed

Takashi Tanaka, Hideo Gobara, Ryota Inai, Toshihiro Iguchi, Akihiro Tada, Shuhei Sato, Hiroyuki Yanai, Susumu Kanazawa

ACTA MEDICA OKAYAMA 70 ( 4 ) 285 - 289 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

We present a case of a 66-year-old man with esophageal carcinoma. (18)Fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) for evaluating distant metastasis and staging revealed F-18-FDG uptake in the third lumbar vertebra and other vertebrae. Magnetic resonance imaging could not differentiate bone metastases from benign bone lesions. We considered the possibility of bone marrow reconversion. (111)Indium chloride (In-111-Cl-3 ) scintigraphy with single-photon emission computed tomography/computed tomography (SPECT/CT) revealed erythroid bone marrow components in the bone lesions. The diagnosis of bone marrow reconversion was pathologically confirmed by a bone biopsy of the third lumbar vertebra. The patient underwent esophagectomy and has remained disease-free in the 2 years since. To the best of our knowledge, this is the first report to describe the usefulness of In-111-Cl-3 with SPECT/CT for the diagnosis of bone marrow reconversion.

DOI： 10.18926/AMO/54505

Expansion of epigenetic alterations in EFEMP1 promoter predicts malignant formation in pancreatobiliary intraductal papillary mucinous neoplasms Reviewed

Kazuhiro Yoshida, Takeshi Nagasaka, Yuzo Umeda, Takehiro Tanaka, Keisuke Kimura, Fumitaka Taniguchi, Tomokazu Fuji, Kunitoshi Shigeyasu, Yoshiko Mori, Hiroyuki Yanai, Takahito Yagi, Ajay Goel, Toshiyoshi Fujiwara

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 142 ( 7 ) 1557 - 1569 2016.7

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Although limited understanding exists for the presence of specific genetic mutations and aberrantly methylated genes in pancreatobiliary intraductal papillary mucinous neoplasms (IPMNs), the fundamental understanding of the dynamics of methylation expansion across CpG dinucleotides in specific gene promoters during carcinogenesis remains unexplored. Expansion of DNA methylation in some gene promoter regions, such as EFEMP1, one of the fibulin family, with tumor progression has been reported in several malignancies. We hypothesized that DNA hypermethylation in EFEMP1 promoter would expand with the tumor grade of IPMN.
A sample of 65 IPMNs and 30 normal pancreatic tissues was analyzed. IPMNs were divided into the following three subsets according to pathological findings: 31 with low-grade dysplasia (low grade), 11 with high-grade dysplasia (high grade), and 23 with associated invasive carcinoma (invasive Ca). Mutations in the KRAS or GNAS genes were analyzed by Sanger sequencing, and methylation status of two discrete regions within the EFEMP1 promoter, namely region 1 and region 2, was analyzed by bisulfite sequencing and fluorescent high-sensitive assay for bisulfite DNA (Hi-SA). Expression status of EFEMP1 was investigated by immunohistochemistry (IHC).
KRAS mutations were detected in 39, 55, and 70 % of low-grade, high-grade, and invasive Ca, respectively. GNAS mutations were observed in 32, 55, and 22 % of low-grade, high-grade, and invasive Ca, respectively. The methylation of individual regions (region 1 or 2) in the EFEMP1 promoter was observed in 84, 91, and 87 % of low-grade, high-grade, and invasive Ca, respectively. However, simultaneous methylation of both regions (extensive methylation) was exclusively detected in 35 % of invasive Ca (p = 0.001) and five of eight IPMNs (63 %) with extensive methylation, whereas 20 of 57 (35.1 %) tumors of unmethylation or partial methylation of the EFEMP1 promoter region showed weak staining EFEMP1 in extracellular matrix (p = 0.422). In addition, extensive EFEMP1 methylation was particularly present in malignant tumors without GNAS mutations and associated with disease-free survival of patients with IPMNs (p < 0.0001).
Extensive methylation of the EFEMP1 gene promoter can discriminate invasive from benign IPMNs with superior accuracy owing to their stepwise accumulation of tumor progression.

DOI： 10.1007/s00432-016-2164-x

A Case of Metastatic Urachal Cancer Including a Neuroendocrine Component Treated with Gemcitabine, Cisplatin and Paclitaxel Combination Chemotherapy Reviewed

Shin Ebara, Yasuyuki Kobayashi, Katsumi Sasaki, Motoo Araki, Morito Sugimoto, Koichirou Wada, Kei Fujio, Atsushi Takamoto, Toyohiko Watanabe, Hiroyuki Yanai, Yasutomo Nasu

ACTA MEDICA OKAYAMA 70 ( 3 ) 223 - 227 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

The present case report describes a case of recurrent and advanced urachal carcinoma including neuroendocrine features with iliac bone metastasis after partial cystectomy and adjuvant chemotherapy consisting of irinotecan and cisplatin in a 32-year-old man. He received gemcitabine/cisplatin/paclitaxel (GCP) combination chemotherapy, consisting of gemcitabin (1,000mg/m(2)) on day 1, 8, cisplatin (70mg/m(2)) on day 1, and paclitaxel (80mg/m(2)) on day 1 and 8. After three cycles of chemotherapy, PET-CT showed complete regression of the disease. So the patient underwent total cystoure-threctomy, and histological examination showed an almost complete pathological response. External beam radiation therapy was also given to the ileac bone metastasis regions. However, PET-CT taken 17 months after the external beam radiation showed multiple lung metastases. He received GCP chemotherapy again, which resulted in a complete response again after three cycles of chemotherapy. This is the first report on GCP chemotherapy used not only as a salvage chemotherapy but also as a rechallenge regimen for metastatic urachal cancer including a neuroendocrine component.

DOI： 10.18926/AMO/54423

Hypocomplementemic urticarial vasculitis arising in a patient with immunoglobulin G4-related disease Reviewed

Mariko Takao, Toshihisa Hamada, Tatsuya Kaji, Kazuko Ikeda-Mizuno, Chinatsu Takehara-Yasuhara, Kouichi Ichimura, Hiroyuki Yanai, Tadashi Yshino, Keiji Iwatsuki

INTERNATIONAL JOURNAL OF DERMATOLOGY 55 ( 4 ) 430 - 433 2016.4

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

BackgroundHypocomplementemic urticarial vasculitis (HUV) has been defined as a syndrome associated with urticarial lesions caused by leukocytoclastic vasculitis. It has been observed in patients with systemic lupus erythematosus and related conditions. Immunoglobulin G4 (IgG4)-related disease is a lymphoproliferative disorder characterized by sclerosing pancreatitis, retroperitoneal fibrosis, sclerotic cholangitis, acute interstitial nephritis, and Mikulicz's disease, and associated with elevated levels of IgG4 and hypocomplementemia. Various cutaneous lesions may occur in IgG4-related disease.
MethodsWe report a 74-year-old woman with HUV, followed by systemic organ involvement suggestive of IgG4-related disease. Symptoms included submandibular gland swelling, lymphadenopathy, interstitial nephritis, and a thyroid nodule. Laboratory examinations revealed an elevated serum IgG4 level of 637mg/dl in a total IgG level of 2176mg/dl, and the production of autoantibodies such as rheumatoid factor and antiphospholipid antibodies. In the swollen lymph node, neither clonal proliferation of T or Bcells nor Epstein-Barr virus infection was detected, although the structure had been destroyed by the infiltration of lymphocytes and plasma cells. Among total IgG-producing cells, approximately 40% were positive for IgG4.
ResultsAll symptoms and abnormal laboratory findings improved in response to oral prednisolone.
ConclusionsHypocomplementemic urticarial vasculitis may represent a clinical symptom of IgG4-related disease.

DOI： 10.1111/ijd.12868

Three histologically distinct cancers of the uterine corpus: A case report and review of the literature. International journal

Hisashi Masuyama, Junko Haraga, Takashi Nishida, Chikako Ogawa, Tomoyuki Kusumoto, Keiichiro Nakamura, Noriko Seki, Hiroyuki Yanai, Yuji Hiramatsu

Molecular and clinical oncology 4 ( 4 ) 563 - 566 2016.4

Language：English Publishing type：Research paper (scientific journal)

Collision tumors, which are characterized by the coexistence of two or more completely distinct and independent tumors in the uterine corpus, are very rare. A collision tumor is mainly composed of two distinct tumor types, epithelial and mesenchymal. To the best of our knowledge, there has only been a single case in which a choriocarcinoma with an endometrial carcinoma were coexistent but histologically distinct. We herein report the first case of a collision tumor in a 52-year-old woman, with a history of two pregnancies and two deliveries. The collision tumor was composed of three histologically distinct neoplasms in the uterine corpus, namely an endometrioid carcinoma, an undifferentiated carcinoma and a choriocarcinoma. The patient underwent hysterectomy, bilateral adnexectomy and pelvic lymph node dissection, followed by six cycles of adjuvant chemotherapy with paclitaxel/carboplatin due to the high risk of endometrial cancer, and an additional five cycles of chemotherapy with methotrexate, as the β-human chorionic gonadotropin level was beyond the normal range. Following adjuvant chemotherapy, the tumor markers were within normal limits and no relapses of the cancer have been observed during 1 year of follow-up. Diagnosing a collision tumor prior to surgery is difficult if the neoplasms are in close proximity, or if one of the tumors predominates. Careful pathological examination is crucial for accurately diagnosing the neoplasms in a collision tumor and ensuring appropriate management and a favorable prognosis.

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