Papers - HIGASHI Michiyo

Naito Y. .  A deep learning model to detect pancreatic ductal adenocarcinoma on endoscopic ultrasound-guided fine-needle biopsy .  Scientific Reports11 ( 1 ) 8454   2021.12

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Publisher：Scientific Reports  

DOI： 10.1038/s41598-021-87748-0

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Noguchi H. .  Rare histological subtype of invasive micropapillary carcinoma in the ampulla of Vater: A case report .  World Journal of Clinical Cases9 ( 11 ) 2671 - 2678   2021.4

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Publisher：World Journal of Clinical Cases  

DOI： 10.12998/wjcc.v9.i11.2671

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Iwaya H. .  Prognostic significance of extracellular volume fraction with equilibrium contrast-enhanced computed tomography for pancreatic neuroendocrine neoplasms .  Pancreatology   2021

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Publisher：Pancreatology  

DOI： 10.1016/j.pan.2021.02.020

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Tasaki T. .  Pulmonary infarction caused by sarcoidosis vascular involvement: A case report .  Pathology International   2021

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Publisher：Pathology International  

DOI： 10.1111/pin.13104

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矢野 弘樹, 橋元 慎一, 田口 宏樹, 田ノ上 史郎, 岩屋 博道, 有馬 志穂, 佐々木 文郷, 上村 修司, 東 美智代, 井戸 章雄 .  膵体部癌との鑑別に難渋し、切除標本により診断し得た2型自己免疫性膵炎の1例 .  膵臓35 ( 5 ) 447 - 454   2020.10膵体部癌との鑑別に難渋し、切除標本により診断し得た2型自己免疫性膵炎の1例

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Publisher：(一社)日本膵臓学会  

症例は46歳女性.心窩部痛,嘔気を主訴に受診した.膵酵素の上昇を認め,急性膵炎の診断で保存的に加療された.画像所見で膵体尾部実質の不均一な造影効果と尾側膵管の拡張を認め,膵腫瘍が疑われた.EUS-FNAにおける組織診断で確定診断が得られなかったが,膵体部癌の可能性が否定できず,手術治療を行った.切除標本にて特徴的な組織所見を示し,2型自己免疫性膵炎の診断に至った.(著者抄録)

Noguchi H. .  Case report of a lymphoepithelioma-like hepatocellular carcinoma with prominent lymphoplasmacytic infiltration .  Human Pathology: Case Reports21   2020.9

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Publisher：Human Pathology: Case Reports  

DOI： 10.1016/j.ehpc.2020.200402

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Sasaki K, Noda M, Tsuruda Y, Uchikado Y, Omoto I, Kita Y, Arigami T, Mori S, Kurahara H, Nakajo A, Higashi M, Ohtsuka T .  Primary monophasic synovial sarcoma of the cervical esophagus confirmed by detection of the SS18-SSX2 fusion transcripts: case report and literature review. .  Surgical case reports6 ( 1 ) 176   2020.7Primary monophasic synovial sarcoma of the cervical esophagus confirmed by detection of the SS18-SSX2 fusion transcripts: case report and literature review.

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DOI： 10.1186/s40792-020-00940-8

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Sasaki Ken, Noda Masahiro, Tsuruda Yusuke, Uchikado Yasuto, Omoto Itaru, Kita Yoshiaki, Arigami Takaaki, Mori Shinichiro, Kurahara Hiroshi, Nakajo Akihiro, Higashi Michiyo, Ohtsuka Takao .  SS18-SSX2融合転写因子の検出によって確定された頸部食道の原発性単相性滑膜肉腫　1症例報告と文献レビュー(Primary monophasic synovial sarcoma of the cervical esophagus confirmed by detection of the SS18-SSX2 fusion transcripts: case report and literature review) .  Surgical Case Reports6   1 of 6 - 6 of 6   2020.7SS18-SSX2融合転写因子の検出によって確定された頸部食道の原発性単相性滑膜肉腫　1症例報告と文献レビュー(Primary monophasic synovial sarcoma of the cervical esophagus confirmed by detection of the SS18-SSX2 fusion transcripts: case report and literature review)

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Publisher：Springer Berlin Heidelberg  

症例は47歳女性で、甲状腺左葉乳頭癌と食道粘膜下腫瘍を検出され当院に紹介された。食道鏡検査で切歯から18cmの部位に径50mmの腫瘍を認め、正常粘膜に被覆され頸部食道左壁に局在していた。造影CTでは限局性の石灰化を有する楕円形の52×34×21mm大の腫瘤を頸部食道に認め、リンパ節腫脹や遠隔転移はみられなかった。甲状腺乳頭癌、頸部食道の平滑筋腫と初期診断を下し、甲状腺左葉切除と食道腫瘍摘出術を施行した。術後の組織学的所見から、食道腫瘍は平滑筋腫と診断した。術後4年、頸部食道腫瘍の再発を認め、内視鏡下生検による顕微観察で紡錘細胞像を呈する非定型細胞浸潤と少数の有糸分裂がみられた。免疫染色所見とあわせ、平滑筋腫ではなく滑膜肉腫が疑われた。さらに、RT-PCR解析を行ったところSS18-SSX2融合転写因子が検出され、頸部食道に生じた単相性滑膜肉腫と診断した。頸部食道切除+空腸間置再建術を行い、病理検査から完全切除を確認した。さらに再手術の3年後、空腸-食道間の吻合遠位部に滑膜肉腫の再発を認め、胸腔鏡下食道切除+胃導管再建後に術後補助化学療法を行った。再々手術の3ヵ月後、再発を認めていない。

笠井 亜衣, 橋元 慎一, 恒吉 研吾, 樺山 雅之, 岩屋 博道, 有馬 志穂, 田口 宏樹, 上村 修司, 東 美智代, 井戸 章雄 .  膵臓の腫瘤性病変に対するEUS-FNAで診断に至ったB細胞リンパ腫の3例 .  膵臓35 ( 2 ) 213 - 221   2020.4膵臓の腫瘤性病変に対するEUS-FNAで診断に至ったB細胞リンパ腫の3例

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Publisher：(一社)日本膵臓学会  

膵原発の悪性リンパ腫は,節外性悪性リンパ腫の2%以下,膵悪性腫瘍の0.5%未満と稀である.画像所見のみでは鑑別が難しく,病理組織学的評価による正確な診断が重要である.今回,膵腫瘤に対し超音波内視鏡下穿刺吸引法(EUS-FNA)でB細胞リンパ腫と診断した3例を経験し,うち2例は化学放射線療法で改善した.EUS-FNAは,リンパ腫の病型診断および治療方針決定に有用と考えられた.(著者抄録)

平野 拓郎, 奥村 浩, 島田 真理緒, 今給黎 亮, 東 美智代, 牧角 寛郎 .  小腸間膜原発デスモイド腫瘍の1切除例 .  鹿児島県臨床外科学会誌31   19 - 22   2020.3小腸間膜原発デスモイド腫瘍の1切除例

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Publisher：鹿児島県臨床外科学会  

58歳男性。右鼠径ヘルニアの術前CT検査で臍下に74mmの辺縁平滑な腫瘤が指摘され、腸間膜腫瘍が疑われた。腹部超音波や腹部造影CT、MRI所見より非上皮系腫瘍が考えられ、由来としては腸間膜が推察され、悪性疾患の可能性から開腹手術が施行された。手術所見では小腸の腸間膜に弾性硬の腫瘤が認められ、近傍の小腸への浸潤もみられたため腫瘤を含めた小腸部分切除術を行った。その結果、病理組織学的に小腸間膜原発デスモイド腫瘍と診断された。目下、術後4ヵ月経過現在、無再発生存中である。尚、本症例はデスモイド腫瘍の発生で多いFAP(家族性大腸ポリポーシス)および開腹手術の既往歴はなかった。

大迫 祐作, 濱之上 雅博, 花園 幸一, 東 美智代, 白濱 浩, 高尾 尊身 .  検診にて発見された早期肝内胆管癌の2切除例 .  鹿児島県臨床外科学会誌31   16 - 18   2020.3検診にて発見された早期肝内胆管癌の2切除例

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Publisher：鹿児島県臨床外科学会  

症例1(70歳代、男性)。検診の腹部超音波検査にて肝外側区に18mm大の低エコー結節を指摘され、二次検診のため当院へ受診となった。CTおよびMRI所見より肝内胆管癌や非典型的な肝細胞癌が疑われ、肝左葉切除術が行われた。症例2(70歳代、女性)。検診の腹部超音波検査にて肝外側区に10mm大の低エコー結節を指摘され、二次検診のため当院へ受診となった。単純CTおよびMRI所見より肝細胞癌や混合型肝癌が疑われ、肝外側区域切除術が行われた。病理組織学的に症例1は早期の肝内胆管癌、症例2は早期の細胆管細胞癌と診断され、それぞれ切除後3年10ヵ月、切除後6ヵ月の時点で無再発生存中である。

Tsubasa Hiraki, Miho Hatanaka, Akiko Arimura, Hisao Kawahira, Mari Kirishima, Ikumi Kitazono, Michiko Horinouchi, Michiyo Higashi, Takuro Kanekura, Akihide Tanimoto .  Granulomatous/sarcoid-like reactions in the setting of programmed cell death-1 inhibition: a potential mimic of disease recurrence. .  Journal of cutaneous pathology47 ( 2 ) 154 - 160   2020.2

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Nivolumab and pembrolizumab are humanized IgG4 monoclonal antibodies against programmed cell death 1 (PD-1). Although these agents are effective in treating advanced melanoma, non-small-cell lung carcinoma, and other types of cancers, various adverse events have been reported. Cutaneous adverse events are particularly prevalent and, while granulomatous/sarcoid-like reactions are uncommon, they are increasingly recognized as immune-related adverse events associated with immune checkpoint inhibitors. Herein, we report two cases of granulomatous/sarcoid-like reaction with foreign material, mimicking metastatic malignancy after PD-1 inhibitor treatment. Clinicians should be aware of the existence of cutaneous lesions and perform biopsy if needed to prevent misdiagnosis and unnecessary adjustments to immunotherapy.

DOI： 10.1111/cup.13569

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Seiya Yokoyama, Taiji Hamada, Michiyo Higashi, Kei Matsuo, Kousei Maemura, Hiroshi Kurahara, Michiko Horinouchi, Tsubasa Hiraki, Tomoyuki Sugimoto, Toshiaki Akahane, Suguru Yonezawa, Marko Kornmann, Surinder K Batra, Michael A Hollingsworth, Akihide Tanimoto .  Predicted Prognosis of Pancreatic Cancer Patients by Machine Learning. .  Clinical cancer research : an official journal of the American Association for Cancer Research26 ( 10 ) 2411 - 2421   2020.1

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PURPOSE: Pancreatic cancer remains a disease of high mortality despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic cancers. MUC1 and MUC4 expression are related to the aggressive behavior of human neoplasms and a poor patient outcome. In contrast, MUC2 is a tumor suppressor, and we have previously reported that MUC2 is a favorable prognostic factor in pancreatic neoplasia. This study investigates whether the methylation status of three mucin genes from postoperative tissue specimens from patients with pancreatic neoplasms could serve as a predictive biomarker for outcome after surgery. EXPERIMENTAL DESIGN: We evaluated the methylation status of MUC1, MUC2, and MUC4 promoter regions in pancreatic tissue samples from 191 patients with various pancreatic lesions using methylation-specific electrophoresis. Then, integrating these results and clinicopathological features, we used support vector machine-, neural network-, and multinomial-based methods to develop a prognostic classifier. RESULTS: Significant differences were identified between the positive- and negative-prediction classifiers of patients in 5-year overall survival (OS) in the cross-validation test. Multivariate analysis revealed that these prognostic classifiers were independent prognostic factors analyzed by not only neoplastic tissues but also non-neoplastic tissues. These classifiers had higher predictive accuracy for OS than tumor size, lymph node metastasis, distant metastasis, and age and can complement the prognostic value of the TNM staging system. CONCLUSIONS: Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with pancreatic ductal adenocarcinoma.

DOI： 10.1158/1078-0432.CCR-19-1247

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和田 真澄, 飯野 聡, 田上 聖徳, 川崎 洋太, 又木 雄弘, 東 美智代, 上野 真一, 夏越 祥次 .  肝内胆管癌と鑑別が困難であった術後13年目の乳癌単発性肝転移切除の1例 .  癌と化学療法47 ( 1 ) 129 - 131   2020.1肝内胆管癌と鑑別が困難であった術後13年目の乳癌単発性肝転移切除の1例

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Publisher：(株)癌と化学療法社  

症例は78歳、女性。65歳時、左乳癌に対して左非定型乳房切除術を施行された。術後5年間内分泌療法が行われ、以後転移再発なく経過していた。術後13年目のCTで肝S4に46mm大の単発性腫瘍を指摘された。腫瘍マーカーの上昇なく、画像検査で肝内胆管癌との鑑別は困難であった。肝内胆管癌であった場合の生検後播種のリスクを考慮し生検は行わず、肝左葉+左尾状葉切除術を施行した。最終病理で乳癌肝転移の診断であった。肝切除術後は内分泌療法を開始し、術後3年無再発生存中である。乳癌術後晩期単発性肝転移はまれであり、肝内胆管癌との鑑別が困難な場合もある。生検による播種のリスクを考慮すると、診断的治療としての肝切除は選択肢になり得る。(著者抄録)

Kurahara H. .  Lung recurrence and its therapeutic strategy in patients with pancreatic cancer: Lung recurrence in pancreatic cancer .  Pancreatology20 ( 1 ) 89 - 94   2020.1

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Publisher：Pancreatology  

DOI： 10.1016/j.pan.2019.11.015

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Wada M, Iino S, Tanoue K, Kawasaki Y, Mataki Y, Higashi M, Ueno S, Natsugoe S .  [Single Liver Metastasis of Breast Cancer Mimicking Intrahepatic Cholangiocarcinoma 13 Years after the Primary Surgery-A Case Report]. .  Gan to kagaku ryoho. Cancer & chemotherapy47 ( 1 ) 129 - 131   2020.1[Single Liver Metastasis of Breast Cancer Mimicking Intrahepatic Cholangiocarcinoma 13 Years after the Primary Surgery-A Case Report].

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Wada M. .  Single liver metastasis of breast cancer mimicking intrahepatic cholangiocarcinoma 13 years after the primary surgery-A case report .  Japanese Journal of Cancer and Chemotherapy47 ( 1 ) 129 - 131   2020.1

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Publisher：Japanese Journal of Cancer and Chemotherapy  

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Kamikihara Y. .  A case of gallbladder neuroendocrine carcinoma diagnosed preoperatively using somatostatin receptor scintigraphy .  Oncology Letters19 ( 1 ) 247 - 254   2020

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Publisher：Oncology Letters  

DOI： 10.3892/ol.2019.11101

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YANO Hiroki, IDO Akio, HASHIMOTO Shinichi, TAGUCHI Hiroki, TANOUE Shiroh, IWAYA Hiromichi, ARIMA Shiho, SASAKI Fumisato, KANMURA Shuji, HIGASHI Michiyo .  Type 2 autoimmune pancreatitis diagnosed after resection and difficult to differentiate from cancer of the pancreatic body .  Suizo35 ( 5 ) 447 - 454   2020

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Publisher：Japan Pancreas Society  

<p>The patient is a 46-year-old woman admitted with epigastric pain and nausea. She was found to have elevated pancreatic enzymes and treated for acute pancreatitis. Imaging findings showed uneven contrast enhancement of the pancreatic body to tail and enlargement of the caudal pancreatic duct. A pancreatic tumor was suspected. Although no definitive histologic diagnosis was obtained using endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA), the possibility of pancreatic body cancer could not be ruled out, and resection was performed. The resected specimen showed characteristic histologic findings, leading to a diagnosis of type 2 autoimmune pancreatitis.</p>

DOI： 10.2958/suizo.35.447

KASAI Ai, IDO Akio, HASHIMOTO Shinichi, TSUNEYOSHI Kengo, KABAYAMA Masayuki, IWAYA Hiromichi, ARIMA Shiho, TAGUCHI Hiroki, KANMURA Shuji, HIGASHI Michiyo .  Three patients with B cell lymphoma diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic lesions .  Suizo35 ( 2 ) 213 - 221   2020

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Publisher：Japan Pancreas Society  

<p>Three patients with pancreatic lymphoma were seen. Primary pancreatic lymphoma accounts for less than 2% of extranodal malignant lymphomas and less than 0.5% of malignant tumors of the pancreas. In patients with pancreatic lymphoma, an accurate diagnosis is crucial because the tumor is difficult to distinguish from other pancreatic tumors-especially pancreatic cancer-based on imaging findings alone, and because the treatment depends on the specific type of lymphoma. Two of these patients improved after chemoradiation therapy. EUS-FNA was useful for determining the type of lymphoma and determining the treatment strategy.</p>

DOI： 10.2958/suizo.35.213

島尾 義也, 堀之内 道子, 東 美智代, 地村 友宏, 永野 広海, 谷本 昭英 .  顎下腺に発生した扁平上皮癌の1例 .  診断病理36 ( 4 ) 320 - 323   2019.10顎下腺に発生した扁平上皮癌の1例

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Publisher：(一社)日本病理学会  

唾液腺、とくに顎下腺に発生する扁平上皮癌は非常に稀である。今回、左顎下腺に発生した扁平上皮癌の1例を経験したので報告する。症例は60代女性、左顎下腺腫瘍の診断で腫瘍摘出術が施行された。腫瘍は浸潤傾向を認め内部に嚢胞様構造を認めた。組織学的には好酸性で厚い細胞質と大型核を有する癌細胞が大小の胞巣を形成し明らかな角化が認められた。CRTC1/CRTC3-MAML2癒合遺伝子は陰性で扁平上皮癌と診断した。唾液腺腫瘍では扁平上皮癌様の形態を示す腫瘍として粘表皮癌や唾液腺導管癌が挙げられ鑑別が必要である。(著者抄録)

Kanmura S, Hamamoto H, Tanaka A, Arima S, Sasaki F, Tanoue S, Nasu Y, Hashimoto S, Higashi M, Ido A .  Diagnostic utility of linked color imaging in the evaluation of colonic mucosal inflammation in ulcerative colitis: a pilot study. .  Endoscopy international open7 ( 8 ) E937 - E943   2019.8Diagnostic utility of linked color imaging in the evaluation of colonic mucosal inflammation in ulcerative colitis: a pilot study.

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DOI： 10.1055/a-0810-0398

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Hirano T, Okumura H, Maeda S, Shimada M, Imakiire A, Makisumi K, Higashi M, Natsugoe S .  Vascular leiomyosarcoma originating from the right ovarian vein: a case report and literature review. .  Surgical case reports5 ( 1 ) 120   2019.7Vascular leiomyosarcoma originating from the right ovarian vein: a case report and literature review.

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DOI： 10.1186/s40792-019-0679-5

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Hirano Takuro, Okumura Hiroshi, Maeda Satoru, Shimada Mario, Imakiire Akira, Makisumi Kanro, Higashi Michiyo, Natsugoe Shoji .  右卵巣静脈原発血管平滑筋肉腫　1症例報告と文献考察(Vascular leiomyosarcoma originating from the right ovarian vein: a case report and literature review) .  Surgical Case Reports5   1 of 6 - 6 of 6   2019.7右卵巣静脈原発血管平滑筋肉腫　1症例報告と文献考察(Vascular leiomyosarcoma originating from the right ovarian vein: a case report and literature review)

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Publisher：Springer Berlin Heidelberg  

右卵巣静脈原発平滑筋肉腫(LMS)の無症状の71歳日本人女性症例について検討した。腹部超音波のルーチン検査において異常所見が認められた。腹部造影CTでは、右腹膜後隙に直径5.5cmの境界明瞭の分葉状充実性腫瘤を認めた。18F-fluorodeoxyglucose PET時、腫瘤の取り込みは比較的低かった。これらの所見に基づき、鑑別診断は類腱腫、平滑筋腫、LMS、悪性中皮腫などの後腹膜腫瘍を含んだ。手術所見により腫瘤が右卵巣血管原発であることを確認し、腫瘤と右卵巣血管の一括切除を実施した。最終的な病理診断は右卵巣静脈原発LMSで、外科切除断端に腫瘍細胞は認めなかった。組織学的所見でLMSの診断を確認した後にアジュバント放射線療法を施行し、術後6ヵ月目経過時点で局所再発または転移の徴候は認められなかった。

Fukukura Y. .  CT and MRI features of undifferentiated carcinomas with osteoclast-like giant cells of the pancreas: a case series .  Abdominal Radiology44 ( 4 ) 1246 - 1255   2019.4

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Publisher：Abdominal Radiology  

DOI： 10.1007/s00261-019-01958-9

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Fukukura Y. .  Extracellular volume fraction determined by equilibrium contrast-enhanced multidetector computed tomography as a prognostic factor in unresectable pancreatic adenocarcinoma treated with chemotherapy .  European Radiology29 ( 1 ) 353 - 361   2019.1

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Publisher：European Radiology  

DOI： 10.1007/s00330-018-5570-4

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霧島 茉莉, 東 美智代, 後藤 優子, 北薗 育美, 平木 翼, 飛田 陽, 谷本 昭英 .  消化管出血で発見された膵十二指腸動静脈奇形の1例 .  診断病理36 ( 1 ) 39 - 45   2019.1消化管出血で発見された膵十二指腸動静脈奇形の1例

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Publisher：(一社)日本病理学会  

45歳男性。消化管出血の精査で十二指腸動静脈奇形を疑われ、経カテーテル動脈塞栓術後に膵頭十二指腸切除術を施行された。切除標本では十二指腸に出血や潰瘍は認めず、割面では十二指腸と膵に拡張した血管を認めた。組織学的には十二指腸から膵実質にかけて静脈様の拡張血管、動脈様血管や不整な小血管の集簇と部分的な吻合がみられ、動静脈奇形(AVM)と診断した。消化管出血を契機に発見された稀な膵十二指腸AVMの1例を報告し、消化管出血との関連について、文献を交えて考察する。(著者抄録)

Toshiaki Akahane, Tomomi Yamaguchi, Yasutaka Kato, Seiya Yokoyama, Taiji Hamada, Yukari Nishida, Michiyo Higashi, Hiroshi Nishihara, Shinsuke Suzuki, Shinichi Ueno, Akihide Tanimoto .  Comprehensive validation of liquid-based cytology specimens for next-generation sequencing in cancer genome analysis. .  PloS one14 ( 6 ) e0217724   2019

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In addition to conventional cytology, liquid-based cytology (LBC) is also used for immunocytochemistry and gene analysis. However, an appropriate method to obtain high quality DNA for next-generation sequencing (NGS) using LBC specimens remains controversial. We determined the optimal conditions for fixation with an alcohol-based fixative for LBC and DNA extraction using cultured cancer cell lines and clinical specimens. The extracted DNA was processed for NGS after the DNA quality was confirmed based on the DNA concentration and degree of degradation. The optimal conditions for cultured cells to obtain high quality DNA were to fix the cells at a density of 6 × 103 or 2 × 104 cells/mL and to use the magnetic bead-based DNA extraction method. Even after storing the fixed cells for 90 days, DNA extracted using the above and other extraction kits, including membrane-based methods, did not undergo degradation. Furthermore, 5-year-old residual LBC samples demonstrated high DNA quality that was suitable for NGS. Furthermore, a cancer genome panel analysis was successfully performed with DNA extracted from cultured cells fixed at 6 × 103 cells/mL for 90 days, and with DNA from residual LBC samples even after 1 year of storage. Residual LBC samples may be a useful source of DNA for clinical NGS to promote genome-based cancer medicine.

DOI： 10.1371/journal.pone.0217724

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Mari Kirishima, Sohsuke Yamada, Mitsuhisa Shinya, Shun Onishi, Yuko Goto, Ikumi Kitazono, Tsubasa Hiraki, Michiyo Higashi, Akira I Hida, Akihide Tanimoto .  An autopsy case of epignathus (immature teratoma of the soft palate) with intracranial extension but without brain invasion: case report and literature review. .  Diagnostic pathology13 ( 1 ) 99 - 99   2018.12

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BACKGROUND: Epignathus is a rare congenital orofacial teratoma infrequently associated with intracranial extension. Intracranial extension of an epignathus indicates a poor prognosis; however, only a small number of such cases have been reported. While there have been some studies reporting cases of epignathus expanding directly into the cranium, others have reported no communication between an epignathus and an intracranial tumor. CASE PRESENTATION: A fetus at gestational week 27 was suspected of having an epignathus with intracranial tumor as shown by ultrasonographic and magnetic resonance imaging. The fetus was stillborn and an autopsy was performed. An epignathus measuring 12 × 6 × 6 cm and weighing 270 g protruded from the mouth, with its base on the soft palate. An intracranial tumor weighing 14 g was located at the middle intracranial fossa and connected to the epignathus through the right side of the sella turcica. The intracranial tumor was encapsulated, and there was no invasion into the brain. Histologically, both the epignathus and intracranial tumor were immature teratomas, with neural and pulmonary components that were especially immature as compared to those of the internal organs and brain tissues of the fetus. CONCLUSION: There have been several reports of epignathus and intracranial tumors that did not communicate; therefore, careful evaluation is needed when a fetus is suspected of having an epignathus extending into an intracranial lesion. Our case supports the findings that an epignathus can directly expand into the cranium. Moreover, this is a rare case of an epignathus in which the intracranial lesion was encapsulated and did not invade the brain. These rare but important findings will provide additional, potential therapeutic strategies for gynecologists, neurosurgeons, and pathologists.

DOI： 10.1186/s13000-018-0776-y

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Kumata Hiroyuki, Murakami Keigo, Ishida Kazuyuki, Miyagi Shigehito, Arakawa Atsushi, Inayama Yoshiaki, Kinowaki Keiichi, Ochiai Atsushi, Kojima Motohiro, Higashi Michiyo, Moritani Suzuko, Kuwahara Kyoko, Nakatani Yukio, Kajiura Dai, Tamura Gen, Kijima Hiroshi, Yamakawa Mitsunori, Shiraishi Taizo, Inadome Yukinori, Murakami Kazuhiro, Suzuki Hiroyoshi, Sawai Takashi, Unno Michiaki, Kamei Takashi, Sasano Hironobu .  肝臓および膵臓粘液性嚢胞性腫瘍の卵巣様間葉系間質におけるステロイド産生(Steroidogenesis in ovarian-like mesenchymal stroma of hepatic and pancreatic mucinous cystic neoplasms) .  Hepatology Research48 ( 12 ) 989 - 999   2018.11肝臓および膵臓粘液性嚢胞性腫瘍の卵巣様間葉系間質におけるステロイド産生(Steroidogenesis in ovarian-like mesenchymal stroma of hepatic and pancreatic mucinous cystic neoplasms)

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Publisher：John Wiley & Sons Australia, Ltd  

肝粘液性嚢胞性腫瘍(MCN)と膵MCNの卵巣様間葉系間質(OLS)におけるステロイド産生について検討した。肝切除術または開窓術後に低悪性度上皮内腫瘍を有する肝MCNと診断した25例(女性、21〜78歳)および低悪性度上皮内腫瘍および遠位膵切除を伴う膵MCN患者24例(女性、23〜65歳)を対象とした。肝MCNは肝内側部分、膵MCNは膵尾部に位置した。エストロゲン受容体(ER)α/ER-β比は、肝MCNおよび膵MCNよりも正常卵巣の方が有意に高く、肝および膵のMCNよりも卵巣MCNの方が高い傾向があった。3β-ヒドロキシステロイドデヒドロゲナーゼHスコアは、膵MCNおよび卵巣MCNよりも肝MCNにおいて有意に高かった。cytochrome P450 17α-hydroxylase/c17-20 lyase(P450c17)Hスコアは、卵巣MCNおよび正常卵巣よりも肝MCNで意に高く、卵巣MCNおよび正常卵巣よりも膵MCNで有意に高かった。5α-レダクターゼ-1 Hスコアは、卵巣MCNおよび正常卵巣よりも肝MCNで有意に高く、卵巣MCNおよび正常卵巣よりも膵MCNで有意に高かった。肝MCNでは、上皮のアンドロゲン受容体(AR)HスコアとOLSのP450c17との間に有意な正の相関が検出された。膵MCNでは、上皮のAR HスコアとOLSのP450c17 Hスコアの間に有意な正の相関が検出された。上皮におけるAR HスコアとOLSにおける5α-レダクターゼ-1 Hスコアとの間に有意な正の相関があった。

Kumata H. .  Steroidogenesis in ovarian-like mesenchymal stroma of hepatic and pancreatic mucinous cystic neoplasms .  Hepatology Research48 ( 12 ) 989 - 999   2018.11

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Publisher：Hepatology Research  

DOI： 10.1111/hepr.13201

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Baba Y. .  Oxidative stress induced by portal vein embolization in fatty liver: Experimental study of a nonalcoholic steatohepatitis model .  Biomedical Reports9 ( 4 ) 357 - 363   2018.10

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Publisher：Biomedical Reports  

DOI： 10.3892/br.2018.1141

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Honjo K. .  PCP4/PEP19 upregulates aromatase gene expression via CYP19A1 promoter I.1 in human breast cancer SK-BR-3 cells .  Oncotarget9 ( 51 ) 29619 - 29633   2018.7

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Publisher：Oncotarget  

DOI： 10.18632/oncotarget.25651

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平木 翼, 宿里 亜李沙, 窪田 恵美, 竹下 かおり, 西田 ゆかり, 田中 和彦, 東 美智代 .  淡明細胞集塊の存在のため、判定に苦慮した子宮頸部扁平上皮癌の一例 .  日本臨床細胞学会九州連合会雑誌49   99 - 100   2018.7淡明細胞集塊の存在のため、判定に苦慮した子宮頸部扁平上皮癌の一例

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Publisher：日本臨床細胞学会-九州連合会  

50歳代、女性。子宮癌検診時の頸部細胞診にてASC-USと判定され、前医を受診した。前医ではハイリスクHPV陽性で、コルポ下生検にてSCCと診断され、精査加療目的で当院へ紹介となった。本症例は組織診断では扁平上皮癌であったにも関わらず、細胞診では多数出現していた淡明細胞の核異型が軽度であったためASC-Hと判定された。しかし、改めて詳細に観察すると、核の腫大、多形性は悪性と判ずるに十分であり、CIN3相当の集塊や角化細胞、対細胞もみられたことからSCCと判定し得たと考えられた。

Kie Honjo, Tsubasa Hiraki, Michiyo Higashi, Hirotsugu Noguchi, Mitsuharu Nomoto, Takuya Yoshimura, Surinder K. Batra, Suguru Yonezawa, Ichiro Semba, Norifumi Nakamura, Akihide Tanimoto, Sohsuke Yamada .  Immunohistochemical expression profiles of mucin antigens in salivary gland mucoepidermoid carcinoma: MUC4-and MUC6-negative expression predicts a shortened survival in the early postoperative phase .  HISTOLOGY AND HISTOPATHOLOGY33 ( 2 ) 201 - 213   2018.2

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Publisher：F HERNANDEZ  

In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when &lt;30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.

DOI： 10.14670/HH-11-913

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Baba Y. .  A new embolic liquid agent comprised of amino acid .  Minimally Invasive Therapy and Allied Technologies27 ( 1 ) 17 - 21   2018.1

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Publisher：Minimally Invasive Therapy and Allied Technologies  

DOI： 10.1080/13645706.2017.1416409

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北薗 育美, 山田 壮亮, 上村 豪, 霧島 茉莉, 後藤 優子, 平木 翼, 東 美智代, 田中 和彦, 松山 篤二, 谷本 昭英 .  捺印細胞診所見の得られたPrimary pulmonary myxoid sarcoma with EWSR1-CREB1 translocationの1例 .  診断病理35 ( 1 ) 79 - 84   2018.1捺印細胞診所見の得られたPrimary pulmonary myxoid sarcoma with EWSR1-CREB1 translocationの1例

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Publisher：(一社)日本病理学会  

症例は60歳代、女性。右肺上葉の18mm大の腫瘍が切除された。組織学的に、豊富な粘液腫状基質を背景に小型類円形〜卵円形核を有する腫瘍細胞の増殖が認められた。RT-PCRでEWSR1-CREB1融合遺伝子が検出され、primary pulmonary myxoid sarcoma with EWSR1-CREB1 translocationと診断した。捺印細胞診では、粘液状基質や炎症細胞を混じる短紡錘形から多角形の異型に乏しい細胞集塊を認め、炎症性変化との鑑別が必要であった。(著者抄録)

後藤 優子, 山田 壮亮, 霧島 茉莉, 北薗 育美, 平木 翼, 東 美智代, 畑中 一仁, 谷本 昭英 .  右肺静脈内に主座を置き左心房内まで達したグロムス腫瘍の稀少な1手術症例 .  診断病理35 ( 1 ) 25 - 30   2018.1右肺静脈内に主座を置き左心房内まで達したグロムス腫瘍の稀少な1手術症例

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Publisher：(一社)日本病理学会  

症例は32歳女性。胸部CTで右肺上葉の末梢から右上肺静脈を経て左心房内に達する数珠状の腫瘍を認め、右肺上葉切除が行われた。切除検体では最大4×2cmの白色充実性の腫瘍であった。組織学的には比較的均一な円形核を有する腫瘍細胞が充実性、シート状構造を呈し、免疫組織化学的にはvimentin、α-SMAにびまん性に強陽性、laminin、h-caldesmonは一部陽性であった。悪性度不明なグロムス腫瘍が肺静脈を経て心房内に達した症例は過去に報告がない。(著者抄録)

Baba Y, Hayashi S, Nagasato K, Higashi M, Tosuji N, Sonoda S, et al. .  Oxidative stress induced by portal vein embolization in fatty liver: Experimental study of a nonalcoholic steatohepatitis model. .  Biomedical reports.9 ( 4 ) 357 - 363   2018Oxidative stress induced by portal vein embolization in fatty liver: Experimental study of a nonalcoholic steatohepatitis model. Reviewed

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

Baba Y, Higashi M, Awai K. .  A new embolic liquid agent comprised of amino acid. Minimally invasive therapy & allied technologies .  official journal of the Society for Minimally Invasive Therapy. 27 ( 1 ) 17 - 21   2018A new embolic liquid agent comprised of amino acid. Minimally invasive therapy & allied technologies Reviewed

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

Nakao Y.M. .  Sex differences in impact of coronary artery calcification to predict coronary artery disease .  Heart104 ( 13 ) 1118 - 1124   2018

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Publisher：Heart  

DOI： 10.1136/heartjnl-2017-312151

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伊地知 徹也, 蔵原 弘, 前村 公成, 又木 雄弘, 川崎 洋太, 迫田 雅彦, 飯野 聡, 上野 真一, 新地 洋之, 東 美智代, 夏越 祥次 .  集学的治療で完全奏効が得られた肝転移を伴うcStage IV膵体部癌の1例 .  日本消化器外科学会雑誌50 ( 11 ) 897 - 904   2017.11集学的治療で完全奏効が得られた肝転移を伴うcStage IV膵体部癌の1例

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Publisher：(一社)日本消化器外科学会  

症例は69歳の女性で,背部痛を主訴に近医を受診し膵腫瘍を指摘され,当科紹介となった.生検結果は腺癌であり,膵体部癌,TS3(35mm),cT3,cS1,cRP1,cPV1(PVp,PVsp),cA1(Asp),cPL1,cN0,cM1(HEP),cStage IVの診断であった.遠隔転移を伴う切除不能膵癌に対してgemcitabine+nab-paclitaxel療法を施行した.6コース施行後に肝転移の消失を確認した.残存する原発巣に対してS-1+放射線療法(56 Gy)を施行し,その後S1による維持療法を施行した.治療開始から12ヵ月後の効果判定ではcomplete response(以下,CRと略記)であり,CA 19-9は1,846U/mlから13.3U/mlまで著明に低下した.組織学的な癌遺残の可能性を考慮し,脾合併膵体尾部切除術+肝部分切除術を施行した.病理組織学的検査では切除した膵臓,肝臓ともに腫瘍細胞を認めず,最終病理診断はCRであった.遠隔転移と局所進行を伴う切除不能膵癌の予後は極めて不良であるが,集学的治療が著効し,病理組織学的CRを得られた症例を経験したので報告する.(著者抄録)

Takashi Tasaki, Kazuhito Hatanaka, Mari Kirishima, Shun Ohnishi, Yuko Goto, Ikumi Kitazono, Tsubasa Hiraki, Sohsuke Yamada, Michiyo Higashi, Akihide Tanimoto .  Aortic fibromuscular dysplasia complicated by dissection: a case report and review of literature .  CARDIOVASCULAR PATHOLOGY31   41 - 46   2017.11

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Publisher：ELSEVIER SCIENCE INC  

Fibromuscular dysplasia (FMD) is an idiopathic, segmental, nonatherosclerotic, non-inflammatory vascular disease, which is often complicated by the occurrence of dissection. Although it is known to occur in all arteries, aortic involvement is relatively rare. To date, 33 cases of aortic FMD have been reported in available English literature, among which only three cases have been complicated by the occurrence of dissection. We describe the case of a 40-year-old woman diagnosed with aortic FMD complicated by the occurrence of a type A aortic dissection. Non-invasive imaging revealed an ascending to descending thoracic aneurysm measuring 8 cm in diameter associated with dissection. Histopathologically, a segment of the wall of the aneurysm showed architectural disorganization of the aortic wall with loss of elastic fibers, collagen deposition, and irregular proliferation of smooth muscle cells in the intima and media-features suggesting FMD. No atheromatous plaque or medial cystic degeneration was observed in the aorta. Although aortic FMD is sometimes fatal, it is often very difficult to diagnose using imaging techniques. Therefore, performing a histopathological diagnosis is very important and should be emphasized. (C) 2017 Published by Elsevier Inc.

DOI： 10.1016/j.carpath.2017.07.007

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Matsuda A, Higashi M, Nakagawa T, Yokoyama S, Kuno A, Yonezawa S, Narimatsu H .  Assessment of tumor characteristics based on glycoform analysis of membrane-tethered MUC1. .  Laboratory investigation; a journal of technical methods and pathology97 ( 10 ) 1262   2017.10Assessment of tumor characteristics based on glycoform analysis of membrane-tethered MUC1.

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DOI： 10.1038/labinvest.2017.67

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Nagano H. .  Bilateral Tibial Osteofibrous Dysplasia on 18F-FDG PET/CT .  Clinical nuclear medicine42 ( 8 ) e375 - e376   2017.8

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Publisher：Clinical nuclear medicine  

DOI： 10.1097/RLU.0000000000001702

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Baba Y, Hayashi S, Nagasato K, Higashi M, Yoshiura T. .  Preliminary experimental study on splenic hemodynamics of radiofrequency ablation for the spleen .  Minim Invasive Ther Allied Technol26 ( 4 ) 193 - 199   2017.8Reviewed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Minimally Invasive Therapy and Allied Technologies  

PURPOSE: To test the splenic blood flow change after radiofrequency ablation (RFA) of the spleen in a porcine experimental model. MATERIAL AND METHODS: Six pigs underwent RFA of the spleen via laparotomy. During the procedure of RFA, clamping of splenic artery (one) and both splenic artery/vein (one) was also performed. Measurement of blood flow of both splenic artery (SA) and splenic vein (SV) with flow-wire at pre- and post-RFA of the spleen was also performed. RESULTS: Ablated splenic lesions were created as estimating approximately 50% area of the spleen in all pigs. Resected specimens reveal not only the coagulated necrosis but also the congestion of the spleen. On the SA hemodynamics, maximum peak velocity (MPV) changed from 37 +/- 7 to 24 +/- 8 cm/s (normal), 11 to 10 cm/s (clamp of the SA), and 12 to 7.5 cm/s (clamp of both SA/SV), respectively. On the SV hemodynamic, MPV changed from 15 +/- 5 to 13 +/- 4 cm/s (normal), 17 to 15 cm/s (clamp of the SA), and 17 to 26 cm/s (clamp of both SA/SV), respectively. CONCLUSIONS: RFA of the spleen could induce coagulation necrosis and reduce the splenic arterial blood flow.

DOI： 10.1080/13645706.2017.1281315

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Other Link： http://www.ncbi.nlm.nih.gov/pubmed/28145148

石神 純也, 柳田 茂寛, 恵 浩一, 橋口 真征, 平野 拓郎, 上之園 芳一, 有上 貴明, 東 美智代, 夏越 祥次 .  難治性腹水を伴った巨大胃GISTの1例 .  日本外科系連合学会誌42 ( 4 ) 632 - 636   2017.8難治性腹水を伴った巨大胃GISTの1例

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Publisher：日本外科系連合学会  

症例は53歳の男性.検診の腹部エコーで多量の腹水と左上腹部に15cm大の腫瘤を指摘され,経超音波内視鏡的生検で胃GISTと診断された.腹水の細胞診は陰性で,明らかな播種病変は指摘できなかった.胃GISTに対して,グリベックと利尿剤を投与したが,内服治療は奏効せず,腹部膨満が増悪し,持続的な腹水穿刺,1日に約1,500ccの排液を要した.腹水原因の精査と腫瘍の根治切除を目的に手術を行った.GIST内の巨大な嚢腫性病変の薄い被膜が穿破しており,嚢胞内部から腹腔内へ嚢胞内溶液が持続的に漏出しており,これが腹水の原因と判明した.腫瘍は胃大彎から茎状に発生しており,横行結腸を圧排,浸潤が疑われた.腫瘍茎部でsafety marginを確保した胃部分切除と浸潤部分の横行結腸を部分切除して,巨大GISTを根治切除した.腫瘍切除により難治性の腹水は完全に消失した.術後経過は良好で,14日目に自宅へ退院となった.巨大胃GISTに伴う難治性腹水の合併は稀であり,報告した.このような病態による腹水のコントロールは手術による腫瘍の切除が有用な治療法と考えられた.(著者抄録)

Seiya Yokoyama, Michiyo Higashi, Hideaki Tsutsumida, Jouji Wakimoto, Tomofumi Hamada, Edwin Wiest, Kei Matsuo, Ikumi Kitazono, Yuko Goto, Xin Guo, Taiji Hamada, Sohsuke Yamada, Tsubasa Hiraki, Suguru Yonezawa, Surinder K Batra, Michael A Hollingsworth, Akihide Tanimoto .  TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer. .  Genes & cancer8 ( 3-4 ) 517 - 527   2017.7Reviewed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Lung cancer remains a disease of high mortality, despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in lung neoplasms. Our immunohistochemistry (IHC) studies have shown that high MUC4 expression correlates with a poor outcome. We have also shown that the expression of several mucin genes in cancer cell lines is regulated by DNA methylation. We evaluated the expression level of MUC4, mRNA and several DNA hypomethylation factors in lung tissue samples from 33 patients with various lung lesions. The results indicated that the DNA methylation status of MUC4 matched the expression level of mRNA. In addition, the TET1 (Ten-Eleven Translocation) mRNA showed a significant correlation with the status of DNA methylation of MUC4. Furthermore, the treatment of a lung cancer cell line with TET1 siRNA caused a reduction in MUC4 mRNA expression. Thus, we suggest that TET1 mediated DNA hypomethylation plays a key role in the expression of MUC4. This is the first report that TET1 mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer. The analysis of these epigenetic changes may be useful for diagnosing carcinogenic risk.

DOI： 10.18632/genesandcancer.139

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PubMed

Other Link： http://www.ncbi.nlm.nih.gov/pubmed/28680536

Hashimoto S, Taguchi H, Higashi M, Hatanaka K, Fujita T, Iwaya H, Nakazawa J, Arima S, Iwashita Y, Sasaki F, Nasu Y, Kanmura S, Ido A. .  Diagnostic efficacy of liquid-based cytology for solid pancreatic lesion samples obtained with endoscopic ultrasound-guided fine-needle aspiration: Propensity score-matched analysis .  Dig Endosc28 ( 5 ) 608 - 616   2017.7

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

BACKGROUND AND AIM: There is a paucity of data on the diagnostic efficacy of liquid-based cytology (LBC) for pancreatic samples obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Using propensity score matching, we retrospectively analyzed the additional diagnostic value of LBC compared to a conventional Papanicolaou smear (CPS) for samples of solid pancreatic lesions obtained by EUS-FNA. METHODS: This cohort study included 126 matched patients who underwent initial EUS-FNA for solid pancreatic lesions between January 2009 and August 2014. CPS was used for cytology of EUS-FNA samples obtained until May 2012 (63 patients). Subsequently, LBC was used for cytological analysis (63 patients). Diagnostic yields of CPS and LBC for malignancy were compared. Risk factors for cytological misdiagnosis with LBC were investigated. RESULTS: Overall rate of malignancy was 86% after matching. LBC had higher diagnostic sensitivity and accuracy than CPS (96.6% vs 84.0%, P = 0.03; and 96.8% vs 87.3%, P = 0.05). LBC was significantly more sensitive for diagnosing pancreatic head lesions (96.4% vs 78.1%, P = 0.04). The sensitivity for pancreatic ductal adenocarcinoma (PDAC) with LBC was higher (98.1% vs 83.0%, P = 0.009). Multivariate analysis revealed that malignant tumors other than PDAC (P = 0.004) and lesion size </=20 mm (P = 0.046) were risk factors for LBC misdiagnosis in all participants. CONCLUSIONS: For solid pancreatic lesions, LBC of EUS-FNA samples contributes to the diagnosis of malignancy. Malignant tumors other than PDAC and small tumors are difficult to diagnose using EUS-FNA and LBC.

DOI： 10.1111/den.12827

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PubMed

Other Link： http://www.ncbi.nlm.nih.gov/pubmed/28160342

Hashimoto Shinichi, Taguchi Hiroki, Higashi Michiyo, Hatanaka Kazuhito, Fujita Toshihiro, Iwaya Hiromichi, Nakazawa Junichi, Arima Shiho, Iwashita Yuji, Sasaki Fumisato, Nasu Yuichiro, Kanmura Shuji, Ido Akio .  超音波内視鏡下穿刺吸引法で採取した膵腫瘤性病変検体に対するliquid-based cytologyの診断的有効性　傾向スコアマッチング解析(Diagnostic efficacy of liquid-based cytology for solid pancreatic lesion samples obtained with endoscopic ultrasound-guided fine-needle aspiration: Propensity score-matched analysis) .  Digestive Endoscopy29 ( 5 ) 608 - 616   2017.7超音波内視鏡下穿刺吸引法で採取した膵腫瘤性病変検体に対するliquid-based cytologyの診断的有効性　傾向スコアマッチング解析(Diagnostic efficacy of liquid-based cytology for solid pancreatic lesion samples obtained with endoscopic ultrasound-guided fine-needle aspiration: Propensity score-matched analysis)

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Publisher：John Wiley & Sons Australia, Ltd  

超音波内視鏡下穿刺吸引法(EUS-FNA)で採取した膵腫瘤性病変検体に対するliquid-based cytology(LBC)法とconventional Papanicolaou smear(CPS)法の診断的有効性を比較するため後向き研究を実施した。対象は2009年1月〜2014年8月に当院で腫瘤性病変に対して初回EUS-FNAを施行した患者126例で、このうち63例は2012年5月迄にCPSによる細胞診を施行し、その後63例にLBCによる細胞診を施行した。悪性腫瘍の全発生率は86%であった。LBCはCPSと比較して感度および正診率が高かった。LBCは膵頭部病変の診断において感度が高かった。膵管腺癌(PDAC)の感度もLBCが高かった。多変量解析により、PDAC以外の悪性腫瘍と20mm以下の病変は全参加者においてLBCによる誤診の危険因子であることが明らかになった。以上から、膵腫瘤性病変に対するEUS-FNAにおいてLBCは悪性腫瘍の診断に有用であるが、PDAC以外の悪性腫瘍と小型腫瘍の場合はEUS-FNAとLBCの診断は困難であることが示された。

宿里 亜李沙, 田中 和彦, 窪田 恵美, 竹下 かおり, 西田 ゆかり, 平木 翼, 山田 壮亮, 東 美智代, 畑中 一仁, 谷本 昭英 .  腎細胞癌根治術後20年で甲状腺内孤立性転移を来たした1例 .  日本臨床細胞学会九州連合会雑誌48   89 - 93   2017.7腎細胞癌根治術後20年で甲状腺内孤立性転移を来たした1例

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Publisher：日本臨床細胞学会-九州連合会  

背景:術後長期を経た腎細胞癌の甲状腺への孤立性転移は非常に稀である。今回、我々は右腎細胞癌術後20年を経過して甲状腺内に孤立性転移を来たした症例を経験したので報告する。症例:70歳代、男性。前医のエコー検査にて甲状腺右葉内に45×41×32mm大の腫瘤を指摘され、当院を紹介受診された。穿刺吸引細胞診では、血性背景に濃縮コロイドや濾胞上皮細胞集塊に混じて、異型細胞が孤在性からシート状にごく少数認められた。異型細胞は淡明で豊富な細胞質と軽度腫大した核を有し、N/C比は小さいながらも核形不整と中心性の明瞭な核小体を認めた。異型細胞はごく少数で、且つ由来が不明であったため、「鑑別困難」(現:意義不明)と報告したところ、経過観察となっていた。その後、嗄声が出現したため再受診され、甲状腺癌による右反回神経麻痺と診断された。生検の結果、腎細胞癌の転移と判明し、CTにて周囲組織への広汎な浸潤が疑われたため、甲状腺全摘出術及び喉頭摘出術が施行された。結論:再検討では淡明細胞型腎細胞癌の細胞像であり、スクリーニング時に充分な情報があれば、腎細胞癌の転移を指摘しえた症例であった。甲状腺の単発性腫瘤であっても、病歴に留意し、腎細胞癌の転移も念頭においたスクリーニングが望まれる。(著者抄録)

Matsuda A, Higashi M, Nakagawa T, Yokoyama S, Kuno A, Yonezawa S, Narimatsu H. .  Assessment of tumor characteristics based on glycoform analysis of membrane-tethered MUC1 .  Lab Invest97 ( 9 ) 1103 - 1113   2017.6Reviewed

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

Clinical tissue specimens are useful for pathological diagnosis, which is, in some cases, supported by visualization of biomolecule localization. In general, diagnostic specificity in molecular pathology is increased by the acquisition of a probe to distinguish the modification of isomers. Although glycosylation is one of the candidate modifications in a protein, comparative glycan analysis of disease-associated proteins derived from a single tissue section is still challenging because of the lack of analytical sensitivity. Here we demonstrate a possible method for differential glycoform analysis of an endogenous tumor-associated glycoprotein MUC1 by an antibody-overlay lectin microarray. Tissue sections (5 mum thick) of patients with cholangiocarcinoma (CCA; n=21) and pancreatic ductal adenocarcinoma (PDAC; n=50) were stained with an anti-MUC1 antibody MY.1E12 that was established as a monoclonal antibody recognizing an MUC1 glycosylation isoform with a sialyl-core 1 structure (NeuAcalpha2-3galactosyl beta1-3-N-acetylgalactosamine). MY.1E12-positive tissue areas (2.5 mm2) were selectively dissected with a laser capture microdissection procedure. The membrane MUC1 was enriched by immunoprecipitation with MY.1E12 and subjected to lectin microarray analysis. Even though the reactivities of MY.1E12 between CCA and PDAC were similar, the lectin-binding patterns varied. We found Maackia amurensis leukoagglutinin and pokeweed lectin distinguished MY.1E12-reactive MUC1 of CCA from that of PDAC. Moreover, MUC1 with M. amurensis hemagglutinin (MAH) reactivity potentially reflected the degree of malignancy. These results were confirmed with MAH-MY.1E12 double fluorescent immunostaining. These glycan changes on MUC1 were detected with high sensitivity owing to the cluster effect of immobilized lectins on a tandem repeat peptide antigen covered with highly dense glycosylation such as mucin. Our approach provides the information to investigate novel glycodynamics in biology, for example, glycoalteration, as well as diseases related to not only MUC1 but also other membrane proteins.Laboratory Investigation advance online publication,

DOI： 10.1038/labinvest.2017.53

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PubMed

Other Link： http://www.ncbi.nlm.nih.gov/pubmed/28581490

平木 翼, 山田 壮亮, 霧島 茉莉, 後藤 優子, 北薗 育美, 畑中 一仁, 東 美智代, 谷本 昭英 .  基底細胞腺腫、篩状亜型の1例 .  診断病理34 ( 2 ) 102 - 105   2017.4基底細胞腺腫、篩状亜型の1例

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Publisher：(一社)日本病理学会  

40代、男性。右耳下腺部に20mm大の可動性良好な腫瘤を認め、摘出術が施行された。周囲とは境界明瞭で、一部に菲薄な線維性被膜を認めた。病変の大部分は基底細胞様細胞が大小の篩状構造を呈し増殖しており、胞巣内には好酸性細胞質を有する導管上皮様細胞からなる真の腺腔も散見された。腺様嚢胞癌や基底細胞腺癌等、篩状構造を示す悪性上皮性唾液腺腫瘍との鑑別が問題となったが、肉眼的に境界明瞭な病変であり、組織学的にも明らかな浸潤性増殖や神経侵襲、脈管侵襲を認めない事から基底細胞腺腫、篩状亜型と診断した。(著者抄録)

中村 達郎, 西川 拓朗, 大吉 達樹, 東 美智代, 有田 和徳, 河野 嘉文 .  vincristine/carboplatinによる化学療法を施行した多発転移病変を伴う線維形成性乳児星細胞腫 .  日本小児血液・がん学会雑誌54 ( 1 ) 39 - 43   2017.4vincristine/carboplatinによる化学療法を施行した多発転移病変を伴う線維形成性乳児星細胞腫

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Publisher：(一社)日本小児血液・がん学会  

症例は5ヵ月の男児。水平性眼振と嘔吐を主訴に受診し、造影CT・MRI検査で両側硬膜下水腫、鞍上部腫瘍、および延髄、脊髄に多発転移病変を認めた。鞍上部腫瘍の生検術により、繊維形成性乳児星細胞腫(DIA:desmoplastic infantile astrocytoma、WHO grade 1)と診断した。低悪性度神経膠腫に対する化学療法レジメンであるvincristine、carboplatin(VC)療法を開始した。すぐに腫瘍径は縮小し始め、治療開始10週後には転移巣も消失した。現在、治療終了後13ヵ月であり、鞍上部腫瘍はわずかに残存するものの、再増大は認めない。現在、症状はなく、精神運動発達の遅れもない。症状を有するDIAに対しては外科的切除が推奨されるが、切除不能もしくは多発転移病変を有するDIAに対してはVC療法が有効な治療法の一つであると考えられた。(著者抄録)

橋口 正史, 玉井 努, 那須 雄一郎, 佐々木 文郷, 東 美智代, 肱黒 薫, 二渡 久智, 重田 浩一朗, 長谷川 将, 井戸 章雄 .  内視鏡的粘膜下層剥離術(endoscopic submucosal dissection)の1年10ヵ月後に異時性肝転移をきたした胃神経内分泌癌(neuroendocrine carcinoma)の1例 .  日本消化器病学会雑誌114 ( 2 ) 238 - 247   2017.2内視鏡的粘膜下層剥離術(endoscopic submucosal dissection)の1年10ヵ月後に異時性肝転移をきたした胃神経内分泌癌(neuroendocrine carcinoma)の1例

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Publisher：(一財)日本消化器病学会  

症例は77歳男性。胃噴門部O-IIc病変にESDを施行、病理診断は深達度SMの分化型優位混在癌、垂直断端(±)のため追加外科切除を施行した。1年10ヵ月後、肝腫瘍を認め肝部分切除を施行、NECと診断された。ESD病変は病理再検討により、胃NECと診断した。Stage IAのR0手術であったが、肝転移再発をきたした。肝切後の補助療法はS-1投与が有効で、1年4ヵ月無再発生存中である。(著者抄録)

Sohsuke Yamada, Mari Kirishima, Tsubasa Hiraki, Michiyo Higashi, Kazuhito Hatanaka, Akihide Tanimoto .  Epithelioid schwannoma of the skin displaying unique histopathological features: a teaching case giving rise to diagnostic difficulties on a morphological examination of a resected specimen, with a brief literature review. .  Diagnostic pathology12 ( 1 ) 11 - 11   2017.1Reviewed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

BACKGROUND: Epithelioid schwannoma as a rare variant poses a challenge to all pathologists, as this uncommon entity is extremely difficult to conclusively diagnose by morphological analyses on a resected sample alone owing to its unique histopathological features. However, few papers have described the detailed clinicopathological characteristics of epithelioid schwannoma. CASE PRESENTATION: A 65-year-old female presented with a history of a flat and slightly elevated firm and tan plaque accompanied by occasional tenderness, measuring 10 × 8 mm, in the right joint of her hand 1 year before resection. A gross examination of a locally resected specimen revealed an encapsulated nodular lesion, yellow-whitish in color, partly filled with blood. A microscopic examination showed that the tumor predominantly consisted of a solid proliferation of epithelioid cells having mildly enlarged and round to partially spindled nuclei and abundant vacuolated or clear cytoplasm with very few mitotic figures and modest nuclear size variation, associated with focal hyalinized, cystic and hemorrhagic degeneration. This well-demarcated tumor was surrounded by dense, hyalinized and layered fibrocollagenous stroma. Immunohistochemically, these tumor cells were diffusely positive for S-100 protein and had a very low MIB-1 labeling index, and type IV collagen was strongly reactive with reduplicated basal lamina of them. We ultimately made a diagnosis of cutaneous epithelioid schwannoma. CONCLUSION: We should be aware that, since pathologists might misinterpret epithelioid schwannoma as other soft tissue tumors, including its malignant counterpart, a wide panel of immunohistochemical antibodies can be powerful supplementary tools for identifying a very rare entity of conventional schwannoma.

DOI： 10.1186/s13000-017-0604-9

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PubMed

Other Link： http://www.ncbi.nlm.nih.gov/pubmed/28103910

Tsubasa Hiraki, Sohsuke Yamada, Michiyo Higashi, Kazuhito Hatanaka, Seiya Yokoyama, Ikumi Kitazono, Yuko Goto, Mari Kirishima, Surinder K. Batra, Suguru Yonezawa, Akihide Tanimoto .  Immunohistochemical expression of mucin antigens in gallbladder adenocarcinoma: MUC1-positive and MUC2-negative expression is associated with vessel invasion and shortened survival .  HISTOLOGY AND HISTOPATHOLOGY32 ( 6 ) 585 - 596   2017.1Reviewed

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

Mucins play pivotal roles in influencing cancer biology, for example affecting carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to investigate the significance of expression profiles of two mucins in particular, MUC1 and MUC2, their correlations with various clinicopathological features, and prognosis in gallbladder adenocarcinoma (GBAC). We performed immunohistochemistry from patients with surgically resected GBAC, using antibodies against mucin core proteins MUC1/DF3 and MUC2/Ccp58 in 81 paraffin-embedded tumor samples. MUC1 or MUC2 expression was considered to be high when &gt;= 20% or 10% of the GBAC cells showed positive staining, respectively. High MUC1 expression was revealed to have a significant relationship to the presence of pathologically lymphatic and vascular invasion, and regional lymph node metastasis. By contrast, high MUC2 expression showed a significant correlation with pathologically perineural invasion, T stage &gt;= 3, and post-operative recurrence. Moreover, MUC1 showed significantly positive co-expression and potentially complementary correlations with MUC2. Multivariate analyses demonstrated that the high MUC1 expression group had significantly shorter disease-specific survival times. However, the combination of both high MUC1 and MUC2 expression did not predict worse outcome in GBACs. Therefore, although each mucin has a somewhat important role in the pathogenesis of GBAC progression, MUC1 can independently predict vessel invasion and poor prognosis in patients with GBAC. The detection of MUC1 might well offer a useful parameter for providing clinical management and treatment against postsurgical GBACs.

DOI： 10.14670/HH-11-824

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PubMed

Ishigami Sumiya, Yanagita Shigehiro, Megumi Koichi, Hashiguchi Motoyuki, Hirano Takuro, Uenosono Yoshikazu, Arigami Takaaki, Higashi Michiyo, Natsugoe Shoji .  A Case of Giant Gastric GIST Concomitant with Refractory Ascites .  Nihon Gekakei Rengo Gakkaishi (Journal of Japanese College of Surgeons)42 ( 4 ) 632 - 636   2017

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Publisher：Japanese College of Surgeons  

<p>A 59-years-old male admitted to Kagoshima Ohshima Hospital with a complaint of Right upper abdomen. Abdominal CT revealed giant gastric GIST 15cm in diameter arising from extra-gastric wall and large amount of fluid collection. Cytology of the fluid revealed negative of malignancy. Imatinib mesylate and diuretics have been administrated to control ascites and to shrink tumor size. However, ascites was aggravated, the patient needed to aspiration and drainage. Giant gastric GIST with ascites unknown etiology was diagnosed preoperatively, R0 resection of gastric GIST was performed. On entering abdominal cavity, small hole was identified in the cystic wall of gastric GIST and translucent fluid was flowed out from the tumor. The tumor was resected with extensive resection of transverse colon and stomach. After the surgery, refractory ascites was improving completely. Refractory ascites derived from the perforative cystic part of the gastric GIST is very rare. Surgery with curative intent is the only way to control fluid collection.</p>

DOI： 10.4030/jjcs.42.632

Hashiguchi M. .  A case of metachronous liver metastasis from neuroendocrine carcinoma of the stomach at 1 year and 10 months after endoscopic submucosal dissection .  Journal of Japanese Society of Gastroenterology114 ( 2 ) 238 - 247   2017

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Publisher：Journal of Japanese Society of Gastroenterology  

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HASHIGUCHI Masafumi, IDO Akio, TAMAI Tsutomu, NASU Yuuichiro, SASAKI Fumisato, HIGASHI Michiyo, HIJIKURO Kaoru, FUTAWATARI Hisatomo, SHIGETA Kouichirou, HASEGAWA Susumu .  A case of metachronous liver metastasis from neuroendocrine carcinoma of the stomach at 1 year and 10 months after endoscopic submucosal dissection .  Nippon Shokakibyo Gakkai Zasshi114 ( 2 ) 238 - 247   2017

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Publisher：The Japanese Society of Gastroenterology  

<p>A 77-year-old man underwent endoscopic submucosal dissection (ESD) of a type 0-IIc tumor located in the cardiac part of the stomach. The pathological diagnosis of the tumor was poorly differentiated tubular adenocarcinoma with submucosal invasion depth;therefore, radical gastrectomy was also performed. After 1 year and 10 months, liver metastasis was detected because of which partial liver resection was performed. The pathological diagnosis of the tumor was neuroendocrine carcinoma (NEC). The pathology of the ESD specimen was re-examined, and a diagnosis of gastric NEC was made;furthermore, the liver tumor was regarded as metachronous metastasis. Despite the radical excision of the stage IA tumor, metastasis occurred. Chemotherapy with S-1 alone was successfully performed after the liver resection while considering the advanced age of the patient. Follow-up revealed no signs of recurrence at 1 year and 4 months after the treatment, indicating that the S-1 therapy may be considered for treating NEC in elderly and medically compromised patients owing to its mild side effects.</p>

DOI： 10.11405/nisshoshi.114.238

PubMed

Idichi Tetsuya, Higashi Michiyo, Natsugoe Shouji, Kurahara Hiroshi, Maemura Kousei, Mataki Yuko, Kawasaki Yota, Sakoda Masahiko, Iino Satoru, Ueno Shinichi, Shinchi Hiroyuki .  Complete Response after Multidisciplinary Therapy for cStage IV Pancreatic Body Cancer with Liver Metastasis .  The Japanese Journal of Gastroenterological Surgery50 ( 11 ) 897 - 904   2017

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Publisher：The Japanese Society of Gastroenterological Surgery  

<p>A 69-year-old woman was initially given a diagnosis of unresectable pancreatic body cancer with liver metastasis and involvement of the celiac plexus. The pretreatment diagnosis according to the General Rules of the Study of Pancreatic Cancer (7th edition) was TS3 (35 mm), cT3, cS1, cRP1, cPV1 (PVp, PVsp), cA1 (Asp), cPL1, cN0, cM1 (HEP), cStage IV. After 6 courses of systemic chemotherapy (gemcitabine and nab-paclitaxel), the liver metastasis disappeared, however, the primary tumor invading the root of the splenic artery remained. Therefore, we performed chemoradiotherapy (CRT: S-1+56 Gy) for further local treatment. After CRT, we continued S-1 administration. Reassessment 12 months after the initial treatment by imaging examinations was complete response (CR). Serum CA 19-9 levels decreased from 1,846 U/ml to 13.3 U/ml. In consideration of remaining histological cancer cells, we performed resection of the pancreatic body and tail with regional lymph node dissection, splenectomy, and partial hepatectomy. Histopathological examination revealed that the tumor was replaced by fibrosis and no cancer cells were observed in the pancreas and liver. The evaluation of histopathological response to the preoperative therapy was CR. The patient remains alive without recurrence at 18 months after initial treatment and 6 months after surgical resection.</p>

DOI： 10.5833/jjgs.2016.0228

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Nakamura Tatsuro, Nishikawa Takuro, Oyoshi Tatsuki, Higashi Michiyo, Arita Kazunori, Kawano Yoshifumi .  Treatment with vincristine/carboplatin for desmoplastic infantile astrocytoma with multiple cerebrospinal metastasis .  The Japanese Journal of Pediatric Hematology / Oncology54 ( 1 ) 39 - 43   2017

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Publisher：The Japanese Society of Pediatric Hematology / Oncology  

<p>In a 5-month-old boy with a history of horizontal nystagmus and vomiting, computed tomography and magnetic resonance imaging (MRI) demonstrated bilateral subdural hygroma and contrast-enhanced lesions in the suprasellar region, medulla oblongata, and the spinal axis. Histopathological examination of a suprasellar tumor biopsy specimen revealed a World Health Organization (WHO) grade I desmoplastic infantile astrocytoma (DIA). A regimen of vincristine and carboplatin (VC) chemotherapy for low-grade astrocytoma was started. The tumor size immediately decreased, and the metastatic lesions also disappeared after the initial 10 weeks of chemotherapy. Although a residual tumor remained in the suprasellar region, no tumor regrowth was detected 13 months after finishing the chemotherapy. The patient showed no symptoms or developmental delay. Although surgical resection is the recommended therapy for symptomatic DIA, our experience suggests that VC chemotherapy might be a therapeutic option for DIA in infants with unresectable tumor or multiple metastasis.</p>

DOI： 10.11412/jspho.54.39

Seiya Yokoyama, Michiyo Higashi, Sho Kitamoto, Monika Oeldorf, Uwe Knippschild, Marko Kornmann, Kosei Maemura, Hiroshi Kurahara, Edwin Wiest, Tomofumi Hamada, Ikumi Kitazono, Yuko Goto, Takashi Tasaki, Tsubasa Hiraki, Kazuhito Hatanaka, Yuko Mataki, Hiroki Taguchi, Shinichi Hashimoto, Surinder K. Batra, Akihide Tanimoto, Suguru Yonezawa, Michael A. Hollingsworth .  Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas .  ONCOTARGET7 ( 27 ) 42553 - 42565   2016.6Reviewed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：IMPACT JOURNALS LLC  

Pancreatic cancer is still a disease of high mortality despite availability of diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic neoplasms. MUC1 and MUC4 are high molecular weight transmembrane mucins. These are overexpressed in many carcinomas, and high expression of these molecules is a risk factor associated with poor prognosis. We evaluated the methylation status of MUC1 and MUC4 promoter regions in pancreatic tissue samples from 169 patients with various pancreatic lesions by the methylation specific electrophoresis (MSE) method. These results were compared with expression of MUC1 and MUC4, several DNA methylation/demethylation factors (e.g. ten-eleven translocation or TET, and activation-induced cytidine deaminase or AID) and CAIX (carbonic anhydrase IX, as a hypoxia biomarker). These results were also analyzed with clinicopathological features including time of overall survival of PDAC patients. We show that the DNA methylation status of the promoters of MUC1 and MUC4 in pancreatic tissue correlates with the expression of MUC1 and MUC4 mRNA. In addition, the expression of several DNA methylation/demethylation factors show a significant correlation with MUC1 and MUC4 methylation status. Furthermore, CAIX expression significantly correlates with the expression of MUC1 and MUC4. Interestingly, our results indicate that low methylation of MUC1 and/or MUC4 promoters correlates with decreased overall survival. This is the first report to show a relationship between MUC1 and/or MUC4 methylation status and prognosis. Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with PDAC.

DOI： 10.18632/oncotarget.9924

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PubMed

Hiraki T, Goto Y, Kitazono I, Tasaki T, Higashi M, Hatanaka K, et al. .  The First Case of Pulmonary Alveolar Proteinosis With Small Cell Lung Carcinoma. .  International journal of surgical pathology. 24 ( 2 ) 135 - 138   2016.4The First Case of Pulmonary Alveolar Proteinosis With Small Cell Lung Carcinoma. Reviewed

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Nakajo M, Nakajo M, Nakayama H, Jinguji M, Nakabeppu Y, Higashi M, et al. .  Dexamethasone Suppression FDG PET/CT for Differentiating between True- and False-Positive Pulmonary and Mediastinal Lymph Node Metastases in Non-Small Cell Lung Cancer: A Pilot Study of FDG PET/CT after Oral Administration of Dexamethasone. .  Radiology.279 ( 1 ) 246 - 253   2016.4Dexamethasone Suppression FDG PET/CT for Differentiating between True- and False-Positive Pulmonary and Mediastinal Lymph Node Metastases in Non-Small Cell Lung Cancer: A Pilot Study of FDG PET/CT after Oral Administration of Dexamethasone. Reviewed

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Masatoyo Nakajo, Masayuki Nakajo, Hirofumi Nakayama, Megumi Jinguji, Yoshiaki Nakabeppu, Michiyo Higashi, Yoshihiro Nakamura, Masami Sato, Takashi Yoshiura .  Dexamethasone Suppression FDG PET/CT for Differentiating between True-and False-Positive Pulmonary and Mediastinal Lymph Node Metastases in Non-Small Cell Lung Cancer: A Pilot Study of FDG PET/CT after Oral Administration of Dexamethasone .  RADIOLOGY279 ( 1 ) 246 - 253   2016.4Dexamethasone Suppression FDG PET/CT for Differentiating between True-and False-Positive Pulmonary and Mediastinal Lymph Node Metastases in Non-Small Cell Lung Cancer: A Pilot Study of FDG PET/CT after Oral Administration of Dexamethasone

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Publisher：RADIOLOGICAL SOC NORTH AMERICA  

Purpose: To examine whether dexamethasone suppression can reduce fluorine 18 fluorodeoxyglucose (FDG) uptake in false-positive (FP) findings in pulmonary and mediastinal lymph nodes in non-small cell lung cancer (NSCLC).
Materials and Methods: Institutional ethics review board approved this prospective study with written informed consent. The study population was composed of 17 patients with NSCLC who underwent both baseline and dexamethasone suppression (24 hours after oral administration of 8 mg dexamethasone) FDG positron emission tomography/computed tomography and surgery. FDG uptake was evaluated by using a five-point visual scoring system (negative findings, score of 0-1; positive findings, score of 2-4) and maximum standardized uptake value (SUVmax). The Mann-Whitney U, Wilcoxon signed-rank, Kruskal-Wallis, or Spearman rank correlation tests were used as necessary for statistical evaluations.
Results: In 17 primary lesions, no significant difference was noted in visual score between baseline (mean, 3.4 +/- 1.2) and dexamethasone suppression scans (mean, 3.3 +/- 1.2; P = .16), although SUVmax was significantly lower on dexamethasone suppression scans (mean, 7.1 +/- 5.2) than on baseline scans (mean, 8.6 +/- 6.6; P = .005). In eight nodes with true-positive (TP) findings, there were no significant differences in visual score (mean for both, 3.8 +/- 0.5) and SUVmax (mean, 5.3 +/- 2.3 vs 5.5 +/- 2.5, respectively; P = .81) between baseline and dexamethasone suppression scans. In 19 nodes with FP findings at baseline, dexamethasone suppression resulted in significantly lowered visual score (mean, 3.4 +/- 0.6 vs 2.4 +/- 0.8, respectively; P &lt; .001) and SUVmax (mean, 3.5 +/- 0.8 vs 2.7 +/- 0.7, respectively; P &lt; .001), and four nodes with FP findings were rated as true-negative findings on dexamethasone suppression scans, which resulted in a significant difference in SUVmax between nodal lesions with TP and FP findings (P = .014).
Conclusion: Oral dexamethasone has the potential to reduce FDG uptake in pulmonary and mediastinal nodes with FP findings in NSCLC. (C) RSNA, 2015

DOI： 10.1148/radiol.2015150883

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Tsubasa Hiraki, Yuko Goto, Ikumi Kitazono, Takashi Tasaki, Michiyo Higashi, Kazuhito Hatanaka, Akihide Tanimoto .  The First Case of Pulmonary Alveolar Proteinosis With Small Cell Lung Carcinoma .  INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY24 ( 2 ) 135 - 138   2016.4The First Case of Pulmonary Alveolar Proteinosis With Small Cell Lung Carcinoma

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Publisher：SAGE PUBLICATIONS INC  

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterized by alveolar accumulation of surfactant lipids and proteins. It is usually autoimmune and secondary to hematologic malignancy or infection. To date, only 5 case reports of PAP associated with lung cancers, including 2 cases of squamous cell carcinoma and 3 cases of adenocarcinoma, have been published. To the best of our knowledge, no case of PAP with small cell lung carcinoma has been reported thus far. We herein report the first case of PAP associated with small cell lung carcinoma.

DOI： 10.1177/1066896915614893

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Matsushita D, Kurahara H, Mataki Y, Maemura K, Higashi M, Iino S, et al. .  Pancreatic hamartoma: a case report and literature review. .  BMC gastroenterology.16 ( 1 ) 3   2016.1Pancreatic hamartoma: a case report and literature review.Reviewed

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Wakiguchi H, Takei S, Imanaka H, Hiraki T, Higashi M, Yamatou T, et al. .  Severe gluteal skin ulcers in an infant with juvenile dermatomyositis. .  European journal of dermatology   2015.12Severe gluteal skin ulcers in an infant with juvenile dermatomyositis. Reviewed

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Hassani S, Castillo A, Ohori J, Higashi M, Kurono Y, Akiba S, et al. .  Molecular Pathogenesis of Human Papillomavirus Type 16 in Tonsillar Squamous Cell Carcinoma. .  Anticancer research. 35 ( 12 ) 6633 - 6638   2015.12Molecular Pathogenesis of Human Papillomavirus Type 16 in Tonsillar Squamous Cell Carcinoma. Reviewed

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Bohara M, Hirabaru M, Fujio S, Higashi M, Yonezawa H, Karki P, et al. .  Choroid Plexus Tumors: Experience of 10 Cases with Special References to Adult Cases. .  Neurologia medico-chirurgica.55 ( 12 ) 891 - 900   2015.12Choroid Plexus Tumors: Experience of 10 Cases with Special References to Adult Cases. Reviewed

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Jinguji M, Kajiya Y, Nakajo M, Higashi M, Yoshiura T. .  A Case of Intraductal Papilloma of the Breast With High 18F-FDG Uptake on PET/CT. .  Clinical nuclear medicine. 40 ( 11 ) 905 - 907   2015.11A Case of Intraductal Papilloma of the Breast With High 18F-FDG Uptake on PET/CT. Reviewed

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北薗 育, 東 美, 平木 翼, 後藤 優, 田崎 貴, 義岡 孝, et al. .  第三脳室脊索腫様膠腫の1例. .  診断病理32 ( 4 ) 285 - 288   2015.10第三脳室脊索腫様膠腫の1例.Reviewed

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Fukukura Y, Shindo T, Higashi M, Takumi K, Umanodan T, Yoneyama T, et al. .  Computed tomography and magnetic resonance imaging features of lipid-rich neuroendocrine tumors of the pancreas. .  World journal of gastroenterology34 ( 21 ) 10008 - 10017   2015.9Computed tomography and magnetic resonance imaging features of lipid-rich neuroendocrine tumors of the pancreas.Reviewed

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坂江 遥, 玉井 努, 宇都 浩, 室町 香, 大西 容, 門野 潤, et al. .  造影超音波検査が有用であった肝原発神経内分泌腫瘍の1例. .  超音波医学42 ( 5 ) 637 - 645   2015.9造影超音波検査が有用であった肝原発神経内分泌腫瘍の1例. Reviewed

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Takumi K, Fukukura Y, Higashi M, Ideue J, Umanodan T, Hakamada H, et al. .  Pancreatic neuroendocrine tumors: Correlation between the contrast-enhanced computed tomography features and the pathological tumor grade. .  Eur J Radiol. 84 ( 8 ) 1436 - 43   2015.8Pancreatic neuroendocrine tumors: Correlation between the contrast-enhanced computed tomography features and the pathological tumor grade. Reviewed

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Higashi M, Yokoyama S, Yamamoto T, Goto Y, Kitazono I, Hiraki T, et al. .  Mucin expression in endoscopic ultrasound-guided fine-needle aspiration specimens is a useful prognostic factor in pancreatic ductal adenocarcinoma. .  pancreas44 ( 53 ) 728 - 734   2015.7Mucin expression in endoscopic ultrasound-guided fine-needle aspiration specimens is a useful prognostic factor in pancreatic ductal adenocarcinoma. Reviewed

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Michiyo Higashi, Seiya Yokoyama, Takafumi Yamamoto, Yuko Goto, Ikumi Kitazono, Tsubasa Hiraki, Hiroki Taguchi, Shinichi Hashimoto, Yoshihiko Fukukura, Chihaya Koriyama, Yuko Mataki, Kosei Maemura, Hiroyuki Shinchi, Maneesh Jain, Surinder K. Batra, Suguru Yonezawa .  Mucin Expression in Endoscopic Ultrasound-Guided Fine-Needle Aspiration Specimens Is a Useful Prognostic Factor in Pancreatic Ductal Adenocarcinoma .  PANCREAS44 ( 5 ) 728 - 734   2015.7Mucin Expression in Endoscopic Ultrasound-Guided Fine-Needle Aspiration Specimens Is a Useful Prognostic Factor in Pancreatic Ductal Adenocarcinoma

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Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objectives The aim of this study was to further examine the utility of mucin (MUC) expression profiles as prognostic factors in pancreatic ductal adenocarcinoma (PDAC).
Methods Mucin expression was examined by immunohistochemistry analysis in endoscopic ultrasound-guided fine-needle aspiration specimens obtained from 114 patients with PDAC. The rate of expression of each MUC was compared with clinicopathologic features.
Results The expression rates of MUCs in cancer lesions were MUC1, 87.7%; MUC2, 0.8%; MUC4, 93.0%; MUC5AC, 78.9%; MUC6, 24.6%; and MUC16, 67.5%. MUC1 and MUC4 were positive, and MUC2 was negative in most PDACs. Patients with advanced stage of PDAC with MUC5AC expression had a significantly better outcome than those who were MUC5AC-negative (P = 0.002). With increasing clinical stage, total MUC6 expression decreased (P for trend = 0.001) and MUC16 cytoplasmic expression increased (P for trend = 0.02). The prognosis of patients with MUC16 cytoplasmic expression was significantly poorer than those without this expression. Multivariate survival analysis revealed that MUC16 cytoplasmic expression was a significant independent predictor of a poor prognosis after adjusting for the effects of other prognostic factors (P = 0.002).
Conclusions Mucin expression profiles in ultrasound-guided fine-needle aspiration specimens have excellent diagnostic utility and are useful predictors of outcome in patients with PDAC.

DOI： 10.1097/MPA.0000000000000362

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Yoshiaki Kamikawa, Yuji Kanmura, Tomofumi Hamada, Norishige Yamada, Muzafar A. Macha, Surinder K. Batra, Michiyo Higashi, Suguru Yonezawa, Kazumasa Sugihara .  Combination of MUC1 and MUC4 expression predicts clinical outcome in patients with oral squamous cell carcinoma .  INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY20 ( 2 ) 298 - 307   2015.4Combination of MUC1 and MUC4 expression predicts clinical outcome in patients with oral squamous cell carcinoma

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Publisher：SPRINGER JAPAN KK  

Both MUC1 and MUC4 are high molecular weight glycoproteins and are independent indicators of worse prognosis in many human epithelial cancers including oral squamous cell carcinoma (OSCC). However, there has been no investigation of the clinical importance of the co-expression of MUC1 and MUC4 in OSCC. The aim of this study was to evaluate the co-expression profile of MUC1/MUC4 and analyze the prognostic significance in OSCC.
We examined the expression profile of MUC1 and MUC4 in OSCC tissues from 206 patients using immunohistochemistry. The co-expression profile of MUC1/MUC4 and its prognostic significance in OSCC was statistically analyzed.
MUC1 and MUC4 overexpression were strongly correlated with each other (p &lt; 0.0001) and a combination of both MUC1 and MUC4 expression was a powerful indicator for tumor aggressiveness such as tumor size (p = 0.014), lymph node metastasis (0.0001), tumor stage (p = 0.006), diffuse invasion (p = 0.028), and vascular invasion (p = 0.014). The MUC1/MUC4 double-positive patients showed the poorest overall and disease-free survival. Multivariate analysis revealed that MUC1/MUC4 double-positivity was the strong independent prognostic factor for overall and disease-free survival (p = 0.007 and (p = 0.0019), in addition to regional recurrence (p = 0.0025).
Taken together, these observations indicate that the use of a combination of MUC1/MUC4 can predict outcomes for patients with OSCC. This combination is also a useful marker for predicting regional recurrence. MUC1 and MUC4 may be attractive targets for the selection of treatment methods in OSCC.

DOI： 10.1007/s10147-014-0710-6

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平木 翼, 後藤 優, 北薗 育, 中村 俊, 東 美, 畑中 一, et al. .  大型異型細胞の出現を伴ったangiofibroma of soft tissueの1例. .  診断病理32 ( 1 ) 36 - 40   2015.1大型異型細胞の出現を伴ったangiofibroma of soft tissueの1例. Reviewed

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Hiroaki Shibahara, Michiyo Higashi, Seiya Yokoyama, Karine Rousseau, Iwao Kitazono, Masahiko Osako, Hiroshi Shirahama, Yukie Tashiro, Yasuhiro Kurumiya, Michihiko Narita, Shingo Kuze, Hiroshi Hasagawa, Takehito Kato, Hitoshi Kubota, Hideaki Suzuki, Toshiyuki Arai, Yu Sakai, Norihiro Yuasa, Masahiko Fujino, Shinji Kondo, Yoshichika Okamoto, Tatsuyoshi Yamamoto, Takashi Hiromatsu, Eiji Sasaki, Kazuhisa Shirai, Satoru Kawai, Koutarou Hattori, Hideki Tsuji, Osamu Okochi, Masaki Sakamoto, Akinobu Kondo, Naomi Konishi, Surinder K. Batra, and Suguru Yonezawa. .  A comprehensive expression analysis of mucins in appendiceal carcinomas in a multi-center study: MUC3 is a novel prognostic factor .  PLOS ONE   2014.12A comprehensive expression analysis of mucins in appendiceal carcinomas in a multi-center study: MUC3 is a novel prognostic factorReviewed

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Hiroaki Shibahara, Michiyo Higashi, Seiya Yokoyama, Karine Rousseau, Iwao Kitazono, Masahiko Osako, Hiroshi Shirahama, Yukie Tashiro, Yasuhiro Kurumiya, Michihiko Narita, Shingo Kuze, Hiroshi Hasagawa, Takehito Kato, Hitoshi Kubota, Hideaki Suzuki, Toshiyuki Arai, Yu Sakai, Norihiro Yuasa, Masahiko Fujino, Shinji Kondo, Yoshichika Okamoto, Tatsuyoshi Yamamoto, Takashi Hiromatsu, Eiji Sasaki, Kazuhisa Shirai, Satoru Kawai, Koutarou Hattori, Hideki Tsuji, Osamu Okochi, Masaki Sakamoto, Akinobu Kondo, Naomi Konishi, Surinder K. Batra, Suguru Yonezawa .  A Comprehensive Expression Analysis of Mucins in Appendiceal Carcinoma in a Multicenter Study: MUC3 Is a Novel Prognostic Factor .  PLOS ONE9 ( 12 ) e115613   2014.12A Comprehensive Expression Analysis of Mucins in Appendiceal Carcinoma in a Multicenter Study: MUC3 Is a Novel Prognostic Factor

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Publisher：PUBLIC LIBRARY SCIENCE  

Background: Mucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma.
Methods: Expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma.
Results: The following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p=0.036); MUC2 with histological type (mucinous carcinoma, p&lt;0.001), superficial invasion depth (p=0.007), negative venous invasion (p=0.003), and curative resection (p=0.019); MUC3 with non-curative resection (p=0.017); MUC5AC with histological type (mucinous carcinoma, p=0.002), negative lymphatic invasion (p=0.021), and negative venous invasion (p=0.022); and MUC16 with positive lymph node metastasis (p=0.035), positive venous invasion (p&lt;0.05), and non-curative resection (p=0.035). A poor prognosis was related to positive lymph node metastasis (p=0.04), positive lymphatic invasion (p=0.02), positive venous invasion (p&lt;0.001), non-curative resection (p&lt;0.001), and positive expression of MUC3 (p=0.004). In multivariate analysis, positive venous invasion (HR: 6.93, 95% CI: 1.93-24.96, p=0.003), non-curative resection (HR: 10.19, 95% CI: 3.05-34.07, p&lt;0.001) and positive MUC3 expression (HR: 3.37, 95% CI: 1.13-10.03, p=0.03) were identified as significant independent prognostic factors in patients with appendiceal carcinoma.
Conclusions: Expression of MUC3 in appendiceal carcinoma is an independent factor for poor prognosis and a useful predictor of outcome in patients with appendiceal carcinoma after surgery.

DOI： 10.1371/journal.pone.0115613

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Masatoyo Nakajo, Masayuki Nakajo, Yoriko Kajiya, Yuko Goto, Megumi Jinguji, Sadao Tanaka, Yoshihiko Fukukura, Atsushi Tani, Michiyo Higashi .  Correlations of F-18-fluorothymidine uptake with pathological tumour size, Ki-67 and thymidine kinase 1 expressions in primary and metastatic lymph node colorectal cancer foci .  EUROPEAN RADIOLOGY24 ( 12 ) 3199 - 3209   2014.12Correlations of F-18-fluorothymidine uptake with pathological tumour size, Ki-67 and thymidine kinase 1 expressions in primary and metastatic lymph node colorectal cancer foci

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Publisher：SPRINGER  

To examine correlations of F-18-fluorothymidine (FLT) uptake with pathological tumour size and immunohistochemical Ki-67, and thymidine kinase 1 (TK-1) expressions in primary and metastatic node colorectal cancer foci.
Thirty primary cancers (PCs) and 37 metastatic nodes (MNs) were included. FLT uptake was assessed by visual scores (non-visible: 0-1 and visible: 2-4), standardized uptake value (SUV), and correlated with size, Ki-67, and TK-1. SUV was measured in visible lesions. FLT heterogeneity was assessed by visual scores (no heterogeneous uptake: 0 and heterogeneous uptake: 1-4).
Forty-two lesions were visible. The visible group showed significantly higher values than the non-visible group in size, Ki-67, and TK-1 (each p &lt; 0.05). Size correlated significantly with visual score (PC; rho = 0.74 and MN; rho = 0.63), SUVmax (PC; rho = 0.49, and MN; rho = 0.76), and SUVmean (PC; rho = 0.40 and MN; rho = 0.76) (each p &lt; 0.05). Visual score correlated significantly with size (rho = 0.86), Ki-67max (rho = 0.35), Ki-67mean (rho = 0.38), TK-1max (rho = 0.35) and TK-1mean (rho = 0.25) (each p &lt; 0.05). No significant correlations were found between FLT uptake and Ki-67 or TK-1 in 42 visible lesions (each p &gt; 0.05). Heterogeneous FLT uptake was noted in 73 % (22/30) of PCs.
FLT uptake correlated with size. Heterogeneous FLT distribution in colorectal cancers may be one of the causes of weak or lack of FLT uptake/Ki-67 or TK-1 correlation.
aEuro cent FLT uptake correlated well with tumour size in colorectal cancer
aEuro cent Weak or lack of FLT uptake/Ki-67 and TK-1 correlations were observed
aEuro cent Immunohistochemical Ki-67 and TK-1 expressions are not always correlated with FLT uptake.

DOI： 10.1007/s00330-014-3379-3

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Higo, K.Kubota, K.Takeda, A.Higashi, M.Ohishi, M. .  Successful antemortem diagnosis and treatment of pulmonary tumor thrombotic microangiopathy .  Intern Med2014 ( 53 ) 2595 - 2599   2014.11Successful antemortem diagnosis and treatment of pulmonary tumor thrombotic microangiopathyReviewed

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橋口 正, 重田 浩, 宇都 浩, 肱黒 薫, 長谷川 将, 風呂井 彰, et al. .  術前診断に経鼻内視鏡を用いた直接経口胆道鏡が有用であったIntraductal papillary neoplasm of the bile ductの一例. .  肝臓55 ( 11 ) 661 - 669   2014.11術前診断に経鼻内視鏡を用いた直接経口胆道鏡が有用であったIntraductal papillary neoplasm of the bile ductの一例.Reviewed

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Hiraki, T. Higashi, M. Goto, Y. Kitazono, I. Yokoyama, S. Iuchi, H. Nagano, H. Tanimoto, A. Yonezawa, S. .  A rare case of internal jugular vein aneurysm with massive hemorrhage in neurofibromatosis type 1 .  Cardiovasc Pathol23 ( 4 ) 244 - 247   2014.7A rare case of internal jugular vein aneurysm with massive hemorrhage in neurofibromatosis type 1Reviewed

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Yokoyama, S.Kitamoto, S.Higashi, M. Goto, Y. Hara, T. Ikebe, D. Yamaguchi, T. Arisaka, Y. Niihara, T. Nishimata, H. Tanaka, S. Takaori, K. Batra, S. K. Yonezawa, S. .  Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice .  PLoS One9 ( 4 ) e93760   2014.4Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juiceReviewed

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Shibahara, H.Higashi, M.Koriyama, C.Yokoyama, S.Kitazono, I.Kurumiya, Y.Narita, M.Kuze, S.Kyokane, T.Mita, S.Arai, T.Kato, T.Yuasa, N.Yamaguchi, R.Kubota, H.Suzuki, H.Baba, S.Rousseau, K.Batra, S. K.Yonezawa, S. .  Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel Cancer .  PLoS One9 ( 4 ) e86111   2014.4Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel CancerReviewed

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Fukukura, Y.Takumi, K.Higashi, M.Shinchi, H.Kamimura, K.Yoneyama, T.Tateyama, A. .  Contrast-enhanced CT and diffusion-weighted MR imaging: Performance as a prognostic factor in patients with pancreatic ductal adenocarcinoma .  Eur J Radiol83 ( 4 ) 612 - 619   2014.4Contrast-enhanced CT and diffusion-weighted MR imaging: Performance as a prognostic factor in patients with pancreatic ductal adenocarcinomaReviewed

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Hiroaki Shibahara, Michiyo Higashi, Chihaya Koriyama, Seiya Yokoyama, Iwao Kitazono, Yasuhiro Kurumiya, Michihiko Narita, Shingo Kuze, Takanori Kyokane, Saburo Mita, Toshiyuki Arai, Takehito Kato, Norihiro Yuasa, Ryuzo Yamaguchi, Hitoshi Kubota, Hideaki Suzuki, Satoshi Baba, Karine Rousseau, Surinder K. Batra, Suguru Yonezawa .  Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel Cancer .  PLOS ONE9 ( 4 ) e86111   2014.4Pathobiological Implications of Mucin (MUC) Expression in the Outcome of Small Bowel Cancer

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Publisher：PUBLIC LIBRARY SCIENCE  

Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p = 0.019), depth (p = 0.017) and curability (p = 0.007)], MUC5AC [tumor location (p = 0.063) and lymph node metastasis (p = 0.059)], and MUC16 [venous invasion (p = 0.016) and curability (p = 0.016)]. Analysis of 58 cases with survival data revealed five factors associated with a poor prognosis: poorly-differentiated or neuroendocrine histological type (p&lt;0.001), lymph node metastasis (p&lt;0.001), lymphatic invasion (p = 0.026), venous invasion (p&lt;0.001) and curative resection (p&lt;0.001), in addition to expression of MUC1 (p = 0.042), MUC5AC (p = 0.007) and MUC16 (p&lt;0.001). In subsequent multivariate analysis with curability as the covariate, lymph node metastasis, venous invasion, and MUC5AC and/or MUC16 expression were significantly related to the prognosis. Multivariate analysis in curative cases (n = 45) showed that SBC with MUC5AC and/or MUC16 expression had a significantly independent high hazard risk after adjusting for the effects of venous invasion (hazard ratio: 5.6, 95% confidence interval: 1.8-17). In conclusion, the study shows that a MUC5AC-positive and/or MUC16-positive status is useful as a predictor of a poor outcome in patients with SBC.

DOI： 10.1371/journal.pone.0086111

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Mizoguchi, T. Kijima, Y. Hirata, M. Kaneko, K. Arima, H. Nakajo, A. Higashi, M. Tabata, K. Koriyama, C. Arigami, T. Uenosono, Y. Okumura, H. Maemura, K. Ishigami, S. Yoshinaka, H. Shinden, Y. Ueno, S. Natsugoe, S. .  Histological findings of an autologous dermal fat graft implanted onto the pectoralis major muscle of a rat model .  Breast Cancer   2014.2Histological findings of an autologous dermal fat graft implanted onto the pectoralis major muscle of a rat modelReviewed

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Michiyo Higashi, Seiya Yokoyama, Takafumi Yamamoto, Yuko Goto, Ikumi Kitazono, Tsubasa Hiraki, Hiroki Taguchi, Shinichi Hashimoto, Yoshihiko Fukukura, Chihaya Koriyama, Yuko Mataki, Kosei Maemura, Hiroyuki Shinchi, Maneesh Jain, Surinder K. Batra and Suguru Yonezawa. .  Mucin (MUC) expression in EUS-FNA specimens is a useful prognostic factor in pancreatic ductal adenocarcinoma .  Pancreas   2014Mucin (MUC) expression in EUS-FNA specimens is a useful prognostic factor in pancreatic ductal adenocarcinomaReviewed

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又木雄弘、新地洋之、前村公成、蔵原弘、川崎洋太、出先亮介、上野真一、迫田雅彦、飯野聡、東美智代、高尾尊身、夏越祥次 .  術前化学(放射線)療法を行った切除可能および境界膵癌の検討 .  癌と化学療法40 ( 12 ) 1637 - 1640   2013.12術前化学(放射線)療法を行った切除可能および境界膵癌の検討Reviewed

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Takumi K, Fukukura Y, Nagasato K, Nakajo M, Natsugoe S, Higashi M. .  Intrahepatic bile duct adenoma mimicking hepatic metastasis: case report and review of the literature. .  Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine.12 ( 2 ) 141 - 145   2013.12Intrahepatic bile duct adenoma mimicking hepatic metastasis: case report and review of the literature.Reviewed

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Iwao Kitazono, Michiyo Higashi, Michiyo, Sho Kitamoto, Seiya Yokoyama, Michiko Horinouchi, Masahiko Osako, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa .  Expression of MUC4 Mucin Is Observed Mainly in the Intestinal Type of Intraductal Papillary Mucinous Neoplasm of the Pancreas .  Pancreas42 ( 7 ) 1120 - 1128   2013.10Expression of MUC4 Mucin Is Observed Mainly in the Intestinal Type of Intraductal Papillary Mucinous Neoplasm of the PancreasReviewed

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Kitazono I, Higashi M, Kitamoto S, Yokoyama S, Horinouchi M, Osako M, Shimizu T, Tabata M, Batra SK, Goto M, Yonezawa S .  Expression of MUC4 mucin is observed mainly in the intestinal type of intraductal papillary mucinous neoplasm of the pancreas. .  Pancreas42 ( 7 ) 1120 - 1128   2013.10Expression of MUC4 mucin is observed mainly in the intestinal type of intraductal papillary mucinous neoplasm of the pancreas.

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DOI： 10.1097/MPA.0b013e3182965915

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Kitamoto S, Yokoyama S, Higashi M, Yamada N, Takao S, Yonezawa S. .  MUC1 enhances hypoxia-driven angiogenesis through the regulation of multiple proangiogenic factors. .  Oncogene32 ( 39 ) 4614 - 4621   2013.9MUC1 enhances hypoxia-driven angiogenesis through the regulation of multiple proangiogenic factors. Reviewed

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平木翼、東美智代、北島信一、前田拓郎、米澤傑 .  小腸と胃に病変を形成したenteropathy-associated T-cell lymphomaの1例 .  診断病理30 ( 3 ) 253 - 257   2013.1小腸と胃に病変を形成したenteropathy-associated T-cell lymphomaの1例Reviewed

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Baba Yasutaka, Hayashi Sadao, Ikeda Shunichiro, Higashi Michiyo, Nakajo Masayuki .  Experimental renal and hepatic artery embolization with a newembolic agent, atelocollagen, in a porcine model .  Diagn Interv Radiol DOI 10.4261/1305-3825.DIR.6086-12.1   2012.12Experimental renal and hepatic artery embolization with a newembolic agent, atelocollagen, in a porcine modelReviewed

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Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa .  MUC4 and MUC1 Expression in Adenocarcinoma of theStomach Correlates with Vessel Invasion and LymphNode Metastasis: An Immunohistochemical Study ofEarly Gastric Cancer .  PLos ONE7 ( 11 )   2012.11MUC4 and MUC1 Expression in Adenocarcinoma of theStomach Correlates with Vessel Invasion and LymphNode Metastasis: An Immunohistochemical Study ofEarly Gastric CancerReviewed

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Yonezawa S, Kitajima S, Higashi M, Osako M, Horinouchi M, Yokoyama S, Kitamoto S, Yamada N, Tamura Y, Shimizu T, Tabata M, Goto M .  A novel anti-MUC1 antibody against the MUC1 cytoplasmic tail domain: use in sensitive identification of poorly differentiated cells in adenocarcinoma of the stomach. .  Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association15 ( 4 ) 370 - 381   2012.10A novel anti-MUC1 antibody against the MUC1 cytoplasmic tail domain: use in sensitive identification of poorly differentiated cells in adenocarcinoma of the stomach.

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DOI： 10.1007/s10120-011-0125-2

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Seiya Yokoyama, Sho Kitamoto, Norishige Yamada, Izumi Houjou, Tamotsu Sugai, Shin-ichi Nakamura, Yoshifumi Arisaka, Kyoichi Takaori, Michiyo Higashi, Suguru Yonezawa .  The application of methylation specific electrophoresis (MSE) to DNA methylation analysis of the 5 ' CpG island of mucin in cancer cells .  BMC CANCER12   67   2012.2The application of methylation specific electrophoresis (MSE) to DNA methylation analysis of the 5 ' CpG island of mucin in cancer cells

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Publisher：BIOMED CENTRAL LTD  

Background: Methylation of CpG sites in genomic DNA plays an important role in gene regulation and especially in gene silencing. We have reported mechanisms of epigenetic regulation for expression of mucins, which are markers of malignancy potential and early detection of human neoplasms. Epigenetic changes in promoter regions appear to be the first step in expression of mucins. Thus, detection of promoter methylation status is important for early diagnosis of cancer, monitoring of tumor behavior, and evaluating the response of tumors to targeted therapy. However, conventional analytical methods for DNA methylation require a large amount of DNA and have low sensitivity.
Methods: Here, we report a modified version of the bisulfite-DGGE (denaturing gradient gel electrophoresis) using a nested PCR approach. We designated this method as methylation specific electrophoresis (MSE). The MSE method is comprised of the following steps: (a) bisulfite treatment of genomic DNA, (b) amplification of the target DNA by a nested PCR approach and (c) applying to DGGE. To examine whether the MSE method is able to analyze DNA methylation of mucin genes in various samples, we apply it to DNA obtained from state cell lines, ethanol-fixed colonic crypts and human pancreatic juices.
Result: The MSE method greatly decreases the amount of input DNA. The lower detection limit for distinguishing different methylation status is &lt; 0.1% and the detectable minimum amount of DNA is 20 pg, which can be obtained from only a few cells. We also show that MSE can be used for analysis of challenging samples such as human isolated colonic crypts or human pancreatic juices, from which only a small amount of DNA can be extracted.
Conclusions: The MSE method can provide a qualitative information of methylated sequence profile. The MSE method allows sensitive and specific analysis of the DNA methylation pattern of almost any block of multiple CpG sites. The MSE method can be applied to analysis of DNA methylation status in many different clinical samples, and this may facilitate identification of new risk markers.

DOI： 10.1186/1471-2407-12-67

Web of Science

PubMed

Seiya Yokoyama, Sho Kitamoto, Norishige Yamada, Izumi Houjou, Tamotsu Sugai, Shin-Ichi Nakamura, Yoshifumi Arisaka, Kyoichi Takaori, Michiyo Higashi, Suguru Yonezawa .  The application of Methylation specific electrophoresis (MSE) to DNA methylation analysis of the 5' CpG island of mucin in cancer cells. .  BMC Cancer   2012.1The application of Methylation specific electrophoresis (MSE) to DNA methylation analysis of the 5' CpG island of mucin in cancer cells.Reviewed

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Michiyo Higashi, Norishige Yamada, Seiya Yokoyama, Sho Kitamoto, Kazuhiro Tabata, Chihaya Koriyama, Surinder K. Batra, and Suguru Yonezawa .  Pathobiological Implications of Expression of MUC16/CA125 in Intrahepatic Cholangiocarcinoma-Mass Forming type .  Pathobiology   2012Pathobiological Implications of Expression of MUC16/CA125 in Intrahepatic Cholangiocarcinoma-Mass Forming typeReviewed

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Kitamoto S, Yokoyama S, Higashi M, Yamada N, Matsubara S, Takao S, Batra SK, Yonezawa S .  Expression of MUC17 is regulated by HIF1α-mediated hypoxic responses and requires a methylation-free hypoxia responsible element in pancreatic cancer. .  PloS one7 ( 9 ) e44108   2012Expression of MUC17 is regulated by HIF1α-mediated hypoxic responses and requires a methylation-free hypoxia responsible element in pancreatic cancer.

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DOI： 10.1371/journal.pone.0044108

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Tamura Y, Higashi M, Kitamoto S, Yokoyama S, Osako M, Horinouchi M, Shimizu T, Tabata M, Batra SK, Goto M, Yonezawa S .  MUC4 and MUC1 expression in adenocarcinoma of the stomach correlates with vessel invasion and lymph node metastasis: an immunohistochemical study of early gastric cancer. .  PloS one7 ( 11 ) e49251   2012MUC4 and MUC1 expression in adenocarcinoma of the stomach correlates with vessel invasion and lymph node metastasis: an immunohistochemical study of early gastric cancer.

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DOI： 10.1371/journal.pone.0049251

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Higashi M, Yamada N, Yokoyama S, Kitamoto S, Tabata K, Koriyama C, Batra SK, Yonezawa S .  Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type. .  Pathobiology : journal of immunopathology, molecular and cellular biology79 ( 2 ) 101 - 106   2012Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type.

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DOI： 10.1159/000335164

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Yonezawa S, Higashi M, Yamada N, Yokoyama S, Kitamoto S, Kitajima S, Goto M .  Mucins in human neoplasms: clinical pathology, gene expression and diagnostic application. .  Pathology international61 ( 12 ) 697 - 716   2011.12Mucins in human neoplasms: clinical pathology, gene expression and diagnostic application.

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DOI： 10.1111/j.1440-1827.2011.02734.x

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Yamada N, Kitamoto S, Yokoyama S, Hamada T, Goto M, Tsutsumida H, Higashi M, Yonezawa S .  Epigenetic regulation of mucin genes in human cancers. .  Clinical epigenetics2 ( 2 ) 85 - 96   2011.8Epigenetic regulation of mucin genes in human cancers.

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DOI： 10.1007/s13148-011-0037-3

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Kitamoto S, Yamada N, Yokoyama S, Houjou I, Higashi M, Goto M, et al. .  DNA methylation and histone H3-K9 modifications contribute to MUC17 expression. .  Glycobiology21 ( 2 ) 247 - 256   2011.2DNA methylation and histone H3-K9 modifications contribute to MUC17 expression.Reviewed

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Kitamoto S, Yamada N, Yokoyama S, Houjou I, Higashi M, Goto M, Batra SK, Yonezawa S .  DNA methylation and histone H3-K9 modifications contribute to MUC17 expression. .  Glycobiology21 ( 2 ) 247 - 256   2011.2DNA methylation and histone H3-K9 modifications contribute to MUC17 expression.

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DOI： 10.1093/glycob/cwq155

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Tsuji T, Togami S, Nomoto M, Higashi M, Fukukura Y, Kamio M, et al. .  Uterine cervical carcinomas associated with lobular endocervical glandular hyperplasia. .  Histopathology59 ( 1 ) 55 - 62   2011.1Uterine cervical carcinomas associated with lobular endocervical glandular hyperplasia.Reviewed

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Yamada N, Nishida Y, Yokoyama S, Tsutsumida H, Houjou I, Kitamoto S, Goto M, Higashi M, Yonezawa S .  Expression of MUC5AC, an early marker of pancreatobiliary cancer, is regulated by DNA methylation in the distal promoter region in cancer cells. .  Journal of hepato-biliary-pancreatic sciences17 ( 6 ) 844 - 854   2010.11Expression of MUC5AC, an early marker of pancreatobiliary cancer, is regulated by DNA methylation in the distal promoter region in cancer cells.

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DOI： 10.1007/s00534-010-0278-0

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Sho Kitamoto, Norishige Yamada, Seiya Yokoyama, Izumi Houjou, Michiyo Higashi, Suguru Yonezawa .  Promoter hypomethylation contributes to the expression of MUC3A in cancer cells .  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS397 ( 2 ) 333 - 339   2010.6Promoter hypomethylation contributes to the expression of MUC3A in cancer cells

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Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

MUC3A is a membrane-bound glycoprotein that is aberrantly expressed in carcinomas and is a risk factor for a poor prognosis. However, the exact mechanism of MUC3A expression has yet to be clarified. Here, we provide the first evidence that MUC3A gene expression is controlled by the CpG methylation status of the proximal promoter region. We show that the DNA methylation pattern is intimately correlated with MUC3A expression in breast, lung, pancreas and colon cancer cell lines. The DNA methylation status of 30 CpG sites from -660 to +273 was mapped using MassARRAY analysis. MUC3A-negative cancer cell lines and those with low MUC3A expression (e.g., MCF-7) were highly methylated in the proximal promoter region, corresponding to 9 CpG sites (-345 to -75 bp), whereas MUC3A-positive cell lines (e.g., LS174T) had low methylation levels. Moreover, 5-aza-2'-deoxycytidine and trichostatin A treatment of MUC3A-negative cells or those with low MUC3A expression caused elevation of MUC3A mRNA. Our results suggest that DNA hypomethylation in the 5'-flanking region of the MUC3A gene plays an important role in MUC3A expression in carcinomas of various organs. An understanding of epigenetic changes in MUC3A may contribute to the diagnosis of carcinogenic risk and to prediction of outcome in patients with cancer. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2010.05.124

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PubMed

Baba M, Castillo A, Koriyama C, Yanagi M, Matsumoto H, Natsugoe S, et al. .  Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas. .  Oncol Rep.23 ( 4 ) 1085 - 1092   2010.4Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas.Reviewed

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Michihiro Baba, Andres Castillo, Chihaya Koriyama, Masakazu Yanagi, Hidehiko Matsumoto, Shoji Natsugoe, Karem Y. Shuyama, Noureen Khan, Michiyo Higashi, Tetsuhiko Itoh, Yoshito Eizuru, Takashi Aikou, Suminori Akiba .  Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas .  ONCOLOGY REPORTS23 ( 4 ) 1085 - 1092   2010.4Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas

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Publisher：SPANDIDOS PUBL LTD  

A number of studies have reported the presence of human papillomavirus (HPV) in lung carcinoma. Interestingly, its detection rate appears to differ histologically and geographically. The present study examined 30 adenocarcinomas and 27 squamous cell carcinomas of the lung in a southern area of Japan, and detected high-risk HPV genome in 9 (30%) adenocarcinomas and 2 (7%) squamous cell carcinomas, using PCR with SPF10 primers and INNO-LiPA HPV genotyping assay. The difference of HPV detection rates in adenocarcinomas and squamous Cell carcinomas was statistically significant (P=0.044, Fisher&apos;s exact test). HPV-16 was the most prevalent HPV genotype. and was detected in 27% (8/30) of adenocarcinomas and in 7% (2/27) of squamous cell carcinomas. High-risk-HPV positive carcinomas had decreased proportions of pRb (P=0.107) and significantly increased proportions of p16(INK4a) expressing cells (P=0.031) when Compared to HPV-negative lung carcinomas. All HPV-16-positive cases were considered to have an integrated form of HPV-16 but its viral load was low (geometric mean = 0.02 copy per cell). In 20 additional adenocarcinomas treated with gefitinib, a tyrosine kinase inhibitor specific for epidermal growth factor receptor, the presence of HPV was examined. Note that East Asian ethnicity is a predictive factor of gefitinib response. High-risk HPV genome was found in 75% (6/8) of adenocarcinomas with complete or partial response to gefitinib but Was not found in the remaining 12, which did not respond to gefitinib. In Conclusion, the present study suggests that high-risk HPV may be more strongly related to adenocarcinomas, particularly gefitinib-responsive adenocarcinomas, when compared to squamous cell carcinomas. However, its low viral load makes it difficult to determine the etiological significance of these findings.

DOI： 10.3892/or_00000736

Web of Science

Higashi M., Goto M., Saitou M., Shimizu T., Rousseau K., Batra S. K., Yonezawa S. .  Immunohistochemical study of mucin expression in periampullary adenomyoma .  J Hepatobiliary Pancreat Sci17 ( 3 ) 275 - 283   2010.3Immunohistochemical study of mucin expression in periampullary adenomyomaReviewed

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Yonezawa S, Higashi M, Yamada N, Yokoyama S, Goto M .  Significance of mucin expression in pancreatobiliary neoplasms. .  Journal of hepato-biliary-pancreatic sciences17 ( 2 ) 108 - 124   2010.3Significance of mucin expression in pancreatobiliary neoplasms.

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DOI： 10.1007/s00534-009-0174-7

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Yonezawa S, Yamada N, Yokoyama S, Kitamoto S, Higashi M, Goto M .  MUC2 (mucin 2, oligomeric mucus/gel-forming) .  Atlas of Genetics and Cytogenetics in Oncology and Haematology14 ( 9 ) 827 - 833   2009MUC2 (mucin 2, oligomeric mucus/gel-forming)

Kijima Y, Yoshinaka H, Higashi M, Yokouchi M, Komiya S, Hisaoka M, Aikou, T.. .  Metastatic breast tumor arising from synovial sarcoma: report of a case. .  Surg Today37 ( 3 ) 230 - 233   2007.3Metastatic breast tumor arising from synovial sarcoma: report of a case. Reviewed

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山田宗茂,浜田倫史,後藤正道,堤田英明,東美智代,野元三治,米澤傑 .  MUC2 expression is regulated by histone H3 modification and DNA methylation in pancreatic cancer .  International Journal of Cancer119 ( 8 ) 1850 - 1857   2006.10MUC2 expression is regulated by histone H3 modification and DNA methylation in pancreatic cancerReviewed

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玉田修吾,柴原弘明,東美智代,後藤正道(GotoMasamichi),バトラ,今井浩三,米澤傑 .  MUC4 is a Novel Prognostic Factor of Extrahepatic Bile Duct Carcinoma .  Clinical Cancer Reserch※ ( ※ ) 4257 - 4264   2006.1MUC4 is a Novel Prognostic Factor of Extrahepatic Bile Duct CarcinomaReviewed

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永田耕治,堀之内道子,斉藤幸,東美智代,野元三治(NomotoMitsuharu),後藤正道(GotoMasamichi),米澤傑 .  Mucins expression profile in pancreatic cancer and the precursor lesions .  Journal of Hepato-Biliary-Pancreatic Surgery※ ( ※ ) ※ - ※   2006.1Mucins expression profile in pancreatic cancer and the precursor lesionsReviewed

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浜田倫史,後藤正道,堤田英明,野元三治,東美智代,菅井有,中村眞一,米澤傑 .  Mapping of the methylation pattern of the MUC2 promoter in pancreatic cancer cell lines, using bisulfite genomic sequencing .  Cancer Letters227 ( 2 ) 175 - 184   2005.2Mapping of the methylation pattern of the MUC2 promoter in pancreatic cancer cell lines, using bisulfite genomic sequencingReviewed

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米澤傑,永田耕治,濱田倫史,野元三治(NomotoMitsuharu),東美智代 .  ムチンに関する最近の考え方-膵腫瘍に関連して-今日用いられるムチンの分析・染色法 .  胆と膵26 ( ※ ) 441 - 449   2005ムチンに関する最近の考え方-膵腫瘍に関連して-今日用いられるムチンの分析・染色法

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有村健,牧野正興,山角麻美,米倉隆治,速見浩士,東美智代,中條政敬(NakajoMasayuki) .  多分割照射が奏功した局所進行膀胱癌の1例． .  癌の臨床．51 ( 12 ) 939 - 941   2005多分割照射が奏功した局所進行膀胱癌の1例．Reviewed

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有村健,牧野正興,山角麻美,中條政敬(NakajoMasayuki),東美智代 .  急速に形成され自然消滅した多発性大陰影を認めた塵肺の1例． .  臨床放射線．50 ( 12 ) 1682 - 1686   2005急速に形成され自然消滅した多発性大陰影を認めた塵肺の1例．Reviewed

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米澤傑,野元三治(NomotoMitsuharu),東美智代 .  病理診断における分子生物学第2部診断への応用と展望A.腫瘍8.膵癌 .  病理と臨床臨時増刊号22 ( ※ ) 147 - 155   2004.1病理診断における分子生物学第2部診断への応用と展望A.腫瘍8.膵癌

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柴原弘明,玉田修吾,東美智代,後藤正道(GotoMasamichi),バトラ,ホリングスワース,今井浩三,米澤傑 .  MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma-mass forming type. .  Hepatology39 ( ※ ) 220 - 229   2004MUC4 is a novel prognostic factor of intrahepatic cholangiocarcinoma-mass forming type.Reviewed

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米澤傑,東美智代,柴原弘明,二村雄次,玉田修吾,後藤正道(GotoMasamichi) .  粘液産生胆管腫瘍の病理 .  肝胆膵49 ( ※ ) 581 - 587   2004粘液産生胆管腫瘍の病理

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Masaaki Kubo, Sonshin Takao, Hiroyuki Shinchi, Keiichirou Uchikura, Michiyo Higashi, Suguru Yonezawa, Takashi Aikou .  Spindle cell carcinoma of the pancreas .  Journal of Hepato-Biliary-Pancreatic Surgery7 ( 2 ) 236 - 241   2000Spindle cell carcinoma of the pancreas

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Publisher：Springer Japan  

We experienced a rare case of spindle cell carcinoma of the pancreas. The patient was a 74-year-old man who complained of abdominal pain and loss of weight. Ultrasonographic scans revealed a hypoechoic solid mass in the head of the pancreas, 4 cm in diameter, with a high echoic spot suggestive of central necrosis or hemorrhage. The mass was hypodense on enhanced computed tomographic scans and hypovascular on angiograms. At laparotomy, the tumor had invaded to the mesocolon, but dissemination and distant metastasis were not found. We therefore performed pylorus-preserving pancreatoduodenectomy and ascending colectomy. The patient was discharged on postoperative day 26 after an uneventful recovery. Two months later, he was readmitted because of ascites, with positivity of spindle cells shown on cytology
he died on day 92 after surgery. In the resected specimen, the tumor had a mostly sarcomatous component, consisting of spindle-shaped cells, and a small glandular component. Immunohistochemically, both components were positive for cytokeratin and epithelial membrane antigen, but negative for vimentin and desmin. The tumor was diagnosed as a spindle cell carcinoma of the pancreas. Perinural invasion, lymphatic permeation, and blood vessel invasion were found, but lymph node metastasis was not found. Although a curative operation was performed, the outcome in this patient was very poor.

DOI： 10.1007/s005340050183

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