論文 - 魏 峻洸
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Gi T., Kuwahara A., Yamashita A., Matsuda S., Maekawa K., Moriguchi-Goto S., Sato Y., Asada Y.
Arteriosclerosis, thrombosis, and vascular biology 43 ( 1 ) 146 - 159 2023年1月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Arteriosclerosis, thrombosis, and vascular biology
BACKGROUND: Cancer-associated venous thromboembolism (VTE) is a critical complication in patients with cancer. However, the pathological findings of VTE are limited. Here, we investigated the histopathological features of cancer-associated VTE in human autopsy cases. METHODS: We clinically examined the autopsy cases of VTE with (n=114) and without cancer (n=66) and immunohistochemically analyzed the expression of prothrombotic factors in intrathrombus cancer cells, the thrombus contents of erythrocytes, fibrin, platelets, citrullinated histone H3, and degree of organization. RESULTS: Vascular wall invasion or small cell clusters of cancer cells was observed in thrombi in 27.5% of deep vein thrombosis and 25.9% of pulmonary embolism cases. The majority of the cancer cells in deep vein thrombi appeared to be invading the vessel wall, whereas the majority of pulmonary thrombi had cancer cell clusters, consistent with embolization via blood flow. These cancer cells were immunohistochemically positive for TF (tissue factors) or podoplanin in up to 88% of VTE cases. The frequency of TF-positive monocyte/macrophages in thrombi was higher in cancer-associated VTE than that in VTE without cancer. Citrullinated histone H3 was predominantly observed in the early stages of organizing thrombi. There was no significant difference in thrombus components between VTE with cancer and without cancer groups. CONCLUSIONS: Vascular wall invasion or cancer cell clusters in thrombi might influence thrombogenesis of cancer-associated VTE. TF and podoplanin in cancer cells and in monocyte/macrophages may induce coagulation reactions and platelet aggregation. Neutrophil extracellular traps may play a role in the early stages of VTE, regardless of cancer status.
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Nobuyuki Oguri, Toshihiro Gi, Eriko Nakamura, Kazunari Maekawa, Eiji Furukoji, Hoshimi Okawa, Sho Kouyama, Saki Horiuchi, Akira Sawaguchi, Tatefumi Sakae, Minako Azuma, Yujiro Asada, Atsushi Yamashita
Research and Practice in Thrombosis and Haemostasis 2025年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：ELSEVIER
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Histological differences among thrombi in thrombotic diseases. 招待あり 査読あり 国際誌
Yamashita A, Gi T, Sato Y
Current opinion in hematology 2025年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Lippincott
PURPOSE OF REVIEW: This review aims to summarize the histological differences among thrombi in acute myocardial infarction, ischemic stroke, venous thromboembolism, and amniotic fluid embolism, a newly identified thrombosis. RECENT FINDINGS: Acute coronary thrombi have a small size, are enriched in platelets and fibrin, and show the presence of fibrin and von Willebrand factor, but not collagen, at plaque rupture sites. Symptomatic deep vein thrombi are large and exhibit various phases of time-dependent histological changes. Cancer-associated venous thromboemboli contain invasive cancer cells that penetrate the vascular walls, and small cancer cell aggregates are observed within the thrombi. The thrombus composition in atherosclerotic and cardioembolic ischemic strokes varies from case to case, while the thrombi in cancer-associated ischemic stroke are rich in platelets and fibrin. A pathological study on amniotic fluid embolism identified uterine vein thrombi and massive platelet-rich microthrombi in the lungs. SUMMARY: Atherothrombus formation is induced by plaque disruption and may occlude a narrow lumen within a short time. Venous thrombi may grow to a large size in a multistage or chronic manner. Cancer cells can directly contribute to venous thrombus formation. The thrombus formation in amniotic fluid embolism may explain the occurrence of consumptive coagulopathy and cardiopulmonary collapse.
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Expression of fibroblast activation protein-α in human deep vein thrombosis 査読あり 国際誌
Oguri N., Gi T., Nakamura E., Furukoji E., Goto H., Maekawa K., Tsuji A.B., Nishii R., Aman M., Moriguchi-Goto S., Sakae T., Azuma M., Yamashita A.
Thrombosis Research 241 109075 2024年9月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Research
Background: Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT. Methods: We performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts. Results: All the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin. Conclusions: The heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity.
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Maekawa K., Nakamura E., Saito Y., Matsuura Y., Gi T., Nishihira K., Oguri N., Moriguchi-Goto S., Sato Y., Hatakeyama K., Shibata Y., Komohara Y., Kaikita K., Asada Y., Yamashita A.
PLoS ONE 20 ( 3 March ) e0316474 2025年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：PLoS ONE
Background The thrombogenic potential of cells within atherosclerotic plaques is critical in the formation of a coronary thrombus. We hypothesized that a combination of inflammatory and hypoxic stimuli enhances tissue factor (TF) expression and glycolysis in cells in atherosclerotic plaques and contributes to coronary thrombus formation. Aims To identify TF- and hexokinase (HK)-II-expressing cells in coronary atherosclerotic plaques and thrombi and determine the effects of combined inflammatory and hypoxic stimuli and glycolysis on TF expression in peripheral blood mononuclear cell-derived macrophages. Methods We immunohistochemically assessed TF and HK-II expression in stable (n = 20) and unstable (n = 24) human coronary plaques and aspirated acute coronary thrombi (n = 15). The macrophages were stimulated with tumor necrosis factor-α, interferon-γ, or interleukin-10 under normoxic (21% O2) or hypoxic (1% O2) conditions, and TF expression was assessed. Results TF and HK-II expression were increased in unstable plaques compared with stable plaques. The number of CD68- and HK-II-immunopositive cells positively correlated with the number of TF-immunopositive cells. TF- and HK-II-expressing macrophages, which expressed M1- or M2-like markers, were involved in platelet-fibrin thrombus formation in ruptured plaques. The combination of inflammatory and hypoxic conditions additively augmented TF expression and procoagulant activity in the cultured macrophages. Inhibition of glycolysis with 2-deoxyglucose reduced the augmented TF expression and procoagulant activity. Conclusion Combined inflammatory and hypoxic conditions in atherosclerotic plaques may markedly enhance procoagulant activity in macrophages and contribute to coronary thrombus formation following plaque disruption. Macrophage TF expression may be associated with glycolysis.
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僧帽弁形成術に関連した左室mesothelial/monocytic incidental cardiac excrescenceの一例 招待あり 査読あり
黒木麻由, 大栗伸行, 中村恵理子, 坂口修平, 魏 峻洸, 阿萬紫, 盛口淸香, 古川貢之, 佐藤勇一郎, 山下篤
診断病理 41 343 - 348 2024年12月
記述言語：日本語 掲載種別：症例報告
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Sugita C., Maekawa K., Gi T., Oguri N., Nakamura E., Furukoji E., Azuma M., Asada Y., Yamashita A.
Thrombosis Research 238 185 - 196 2024年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Research
Background: Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques. Aims: We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits. Methods and results: We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5′-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group. Conclusions: Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.
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Paratesticular cellular angiofibroma: a case report 査読あり 国際誌
Murashima T., Kida K., Gi T., Hida T., Fujii M., Nagai T., Takamori H., Mukai S., Sato Y., Kamoto T.
Journal of Medical Case Reports 18 ( 1 ) 170 2024年4月
記述言語：英語 掲載種別：症例報告 出版者・発行元：Journal of Medical Case Reports
Introduction: Paratesticular cellular angiofibroma is a rare benign mesenchymal tumor. The optimal management is surgical resection due to the difficulty of preoperative accurate diagnosis. Case presentation: A 51-year-old Japanese male visited our hospital complaining of asymptomatic left scrotal swelling. Physical examination revealed a nontender elastic paratesticular mass (5.5 cm in diameter). Although testicular germ cell tumor was ruled out clinically, the possibility of malignant potential remained for the tumor. Since the patient consented to complete resection, a transinguinal radical orchiectomy was performed. The pathological diagnosis revealed cellular angiofibroma. The patient recovered without perioperative complications, and no apparent recurrence was observed at 5 years after surgery. Conclusion: The pathological findings were compatible for cellular angiofibroma. The tumor was successfully resected, and no apparent recurrence was observed at 5 years after surgery.
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がん関連静脈血栓塞栓における血栓内がん細胞の存在 招待あり 査読あり
魏 峻洸
日本血栓止血学会誌 35 ( 4 ) 512 - 521 2024年
担当区分：筆頭著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本血栓止血学会
がん関連静脈血栓塞栓症（がん関連venous thromboembolism: VTE）は，担癌患者における致死的な病態の一つであるが，血栓部位の病理学的検討は極めて少ない．本研究ではVTEの剖検症例を用いて病理組織学的検討を行った．がん関連VTEでは，約3割の症例で血栓中にがん細胞を認め，血管周囲組織からの直接浸潤によるもの，あるいは小集簇性に存在していた．また，血栓内がん細胞の約4割に腫瘍壊死を認め，ダメージ関連分子パターン（DAMPs）放出が示唆された．免疫組織化学では，血栓内がん細胞には，組織因子あるいはポドプラニンの発現を約9割に認めた．これらの結果から，直接浸潤による血管壁の破壊や経血流的に侵入したがん細胞が組織因子，ポドプラニン，DAMPsを発現することで，凝固反応・血小板凝集を促進し，がん関連VTEの病態に直接的に寄与することが示唆された．
DOI： 10.2491/jjsth.35.512
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Yamashita A., Oda T., Aman M., Wakasa T., Gi T., Ide R., Todo Y., Tamura N., Sato Y., Itoh H., Asada Y.
BJOG: An International Journal of Obstetrics and Gynaecology 130 ( 13 ) 1685 - 1696 2023年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BJOG: An International Journal of Obstetrics and Gynaecology
Objective: To identify pulmonary/uterine thrombus formation in amniotic fluid embolism (AFE). Design: Retrospective, observational. Setting: Nationwide. Population: Eleven autopsy cases of AFE and control cases. Methods: We assessed pulmonary and uterine thrombus formation and thrombus area in AFE and pulmonary thromboembolism (PTE) as a control. The area of platelet glycoprotein IIb/IIIa, fibrin, neutrophil elastase, citrullinated histone H3 (a neutrophil extracellular trap marker) and mast cell chymase immunopositivity was measured in 90 pulmonary emboli, 15 uterine thrombi and 14 PTE. Main outcome measures: Pathological evidence of thrombus formation and its components in AFE. Results: Amniotic fluid embolism lung showed massive thrombus formation, with or without amniotic emboli in small pulmonary arteries and capillaries. The median pulmonary thrombus size in AFE (median, 0.012 mm2; P < 0.0001) was significantly smaller than that of uterine thrombus in AFE (0.61 mm2) or PTE (29 mm2). The median area of glycoprotein IIb/IIIa immunopositivity in pulmonary thrombi in AFE (39%; P < 0.01) was significantly larger than that of uterine thrombi in AFE (23%) and PTE (15%). The median area of fibrin (0%; P < 0.001) and citrullinated histone H3 (0%; P < 0.01) immunopositivity in pulmonary thrombi in AFE was significantly smaller than in uterine thrombi (fibrin: 26%; citrullinated histone H3: 1.1%) and PTE (fibrin: 42%; citrullinated histone H3: 0.4%). No mast cells were identified in pulmonary thrombi. Conclusions: Amniotic fluid may induce distinct thrombus formation in the uterus and lung. Pulmonary and uterine thrombi formation may contribute to cardiorespiratory collapse and/or consumptive coagulopathy in AFE.
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症例 ペムブロリズマブによる免疫関連有害事象と考えられたHypertrophic Lichen Planusの1例 招待あり
後田 優香, 西川 陽太郎, 野海 健太, 魏 峻洸, 天野 正宏
皮膚科の臨床 65 ( 12 ) 1896 - 1899 2023年11月
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Soejima H., Ogawa H., Morimoto T., Okada S., Matsumoto C., Nakayama M., Masuda I., Jinnouchi H., Waki M., Saito Y., Miwa K., Akahoshi K., Misumi K., Araki H., Mitsudo Y., Kondo N., Ashihara K., Yumoto S., Horimoto M., Doi O., Doijiri K., Fukami R., Shimabukuro M., Egusa G., Goto K., Hanaoka Y., Kimura Y., Haraguchi Y., Haraguchi O., Hasegawa A., Shioya Y., Shioya Y., Tanaka E., Yamada K., Atsumi T., Tanazawa S., Horio Y., Ichihara S., Yasuda I., Ikeda T., Ikemura M., Imamoto C., Iseri Y., Iwai K., Okamoto S., Sugiyama S., Kamura M., Kan H., Kiyota M., Kawamura K., Ono T., Koga T., Kinuwaki E., Naito H., Kozuma K., Kudou K., Morikami Y., Yasue H., Mizuno Y., Fujimoto H., Matsuyama K., Fujii H., Kamijikkoku S., Kuwahara T., Takaoka K., Machii K., Maeda K., Mahara K., Maki A., Manda N., Marutsuka K., Sameshima N., Gi T., Matsunaga T., Matsuo S., Okubo H., Minagawa F., Minoda K., Miyata J., Matsuo T., Momosaki S., Munakata T., Nakamura T., Nagano H., Goshi K., Sugimoto K., Naomi S., Nasu T., Tanaka H., Sonoda R., Kajiwara K., Odo T., Ogata H., Ogihara M., Ogura T., Oka K., Kawashima E., Oshima E., Ozaki K., Ozawa S.
Heart and Vessels 38 ( 11 ) 1371 - 1379 2023年11月
掲載種別：研究論文（学術雑誌） 出版者・発行元：Heart and Vessels
Background: Dipeptidyl Peptidase-4 (DPP-4) inhibitors do not suppress cardiovascular events in diabetic patients with a history of cardiovascular disease. However, the effect of DPP-4 inhibitors on cardiovascular events in Japanese diabetic patients is unclear. Therefore, we investigated whether DPP-4 inhibitors alter the incidence of cardiovascular events in Japanese diabetic patients without a history of cardiovascular events. Methods: The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study conducted from 2002 to 2008. After completion of the JPAD trial, we followed up the patients until 2019. Patients who had had a cardiovascular event by the 2013 follow-up were excluded from the study. JPAD patients were divided into a DPP-4 group and a non-DPP-4 group based on whether they were taking DPP-4 inhibitors at the 2013 follow-up because few patients took DPP-4 inhibitors before 2013. We investigated the incidence of cardiovascular events consisting of coronary events, cerebrovascular events, heart failure requiring hospitalization, and aortic and peripheral vascular disease in 1099 JPAD patients until 2019. Results: During the observation period from 2013 to 2019, 37 (7%) first cardiovascular events occurred in the DPP-4 group (n = 518) and 66 (11%) in the non-DPP-4 group (n = 581). The incidence of cardiovascular events was significantly lower in the DPP-4 group than in the non-DPP-4 group (Log-Rank P = 0.0065). Cox proportional hazards model analysis revealed that the use of DPP-4 inhibitors (hazard ratio 0.65; 95% confidence interval 0.43–0.98; P = 0.038) was an independent factor after adjustment for age ≥ 65 years, hypertension, statin usage, and insulin usage. Conclusions: Our findings have demonstrated that the use of DPP-4 inhibitors may be associated with a reduced incidence of first cardiovascular events in Japanese diabetic patients. The results require confirmation in randomized controlled trials.
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Shimazu H., Matsuura Y., Moribayashi K., Gi T., Suiko Y., Tanaka H., Komaki S., Ishikawa T., Yamashita A., Kaikita K.
JACC: Case Reports 24 102017 2023年10月
記述言語：英語 掲載種別：症例報告 出版者・発行元：JACC: Case Reports
Immune thrombocytopenia (ITP) carries bleeding and thrombotic risks; however, thromboses associated with ITP have not been histologically examined. This report presents optical coherence tomography images of the culprit lesion and histology of coronary aspirates in very late stent thrombosis complicating severe ITP, providing evidence of platelet-rich thrombus formation. (Level of Difficulty: Advanced.)
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Magnetic Resonance Imaging of Cancer-Associated Deep Vein Thrombus in a Patient With Gastric Cancer. 査読あり 国際誌
Gi T, Kuroiwa Y, Kihara Y, Miyaushiro S, Yamashita A
Circulation reports 5 ( 6 ) 265 - 266 2023年6月
担当区分：筆頭著者 記述言語：英語 掲載種別：症例報告 出版者・発行元：一般社団法人 日本循環器学会
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症例報告 ボリコナゾール長期内服による多発有棘細胞癌の治療中に生じたMerkel細胞癌の1例 査読あり
森 愛菜, 持田 耕介, 西川 陽太郎, 中村 俊央, 魏 峻洸, 河野 徳明, 天野 正宏
臨床皮膚科 77 ( 6 ) 433 - 438 2023年5月
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ボリコナゾール長期内服による多発有棘細胞癌の治療中に生じたMerkel細胞癌の1例
森 愛菜, 持田 耕介, 西川 陽太郎, 中村 俊央, 魏 峻洸, 河野 徳明, 天野 正宏
臨床皮膚科 77 ( 6 ) 433 - 438 2023年5月
記述言語：日本語 掲載種別：症例報告 出版者・発行元：(株)医学書院
＜文献概要＞47歳,男性.11年前に急性骨髄性白血病に対して,同種骨髄移植および臍帯血移植を施行された.5年前より肺深在性真菌症に対してボリコナゾール(VRCZ)内服開始,その3年後に頭部に紅斑,びらん,4年後に多発有棘細胞癌(squamous cell carcinoma: SCC)を生じた.VRCZと紫外線の影響を考え内服中止し,イトラコナゾールへ変更した.多発するSCCは切除施行した.外来通院中に左頸部に1cm大の腫瘤が出現し,全摘生検施行し,Merkel細胞癌(Merkel cell carcinoma: MCC)と診断した.VRCZの長期投与と紫外線の影響はSCC発生のリスク因子と報告されているが,MCCを発症した報告は,医中誌やPubMedで検索した限り,自験例を除き1例しかない.さらに,VRCZの長期投与後にSCCとMCCが併発した症例は自験例以外に報告はなく,発症後はMCCの比較的急速な病勢の進行を認めることから,同様な病態では慎重な経過観察と早期の治療が必要である.
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肺気管支にSolitary fibrous tumorとIntercalated duct hyperplasiaの合併を認めた1例
佐藤 勇一郎, 黒木 将英, 前田 亮, 魏 峻洸, 山下 篤, 浅田 祐士郎
診断病理 40 ( 1 ) 96 - 100 2023年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：(一社)日本病理学会
Intercalated duct hyperplasia(IDH)は,唾液腺で提唱され,顕微鏡的に偶然発見される病変である。70歳代男性。今回肺切除術後の病理検体で,右上葉気管支壁にSolitary fibrous tumor(SFT)とともに最大径4mmの介在導管に類似した二相性の細胞からなる気管支腺の増生を認め,IDHと診断した。IDHはまれな病変で,これまで唾液腺以外の報告はなく,貴重な症例と思われた。(著者抄録)
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診断に難渋したUterine tumor resembling ovarian sex cord tumorの1例
佐藤 勇一郎, 魏 峻洸, 松澤 聡史, 藤崎 碧, 川越 靖之, 大西 淳仁, 桂木 真司
日本婦人科病理学会誌 13 ( 2 ) 73 - 76 2022年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本婦人科病理学会
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Intrapulmonary solitary fibrous tumor coexisting with lung adenocarcinomas. 査読あり 国際誌
Kuroki S, Ayabe T, Gi T, Sato Y, Nakada H, Maeda R
Surgical case reports 8 ( 1 ) 150 2022年8月
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Tomimori-Gi K, Katsuragi S, Kodama Y, Yamada N, Sameshima H, Maekawa K, Yamashita A, Gi T, Sato Y
Virchows Archiv 481 ( 5 ) 713 - 720 2022年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Virchows Archiv
Preeclampsia, a multisystem pregnancy-specific hypertensive disorder, results in significant maternal and perinatal morbidity and mortality. This condition is associated with placental histopathological abnormalities and particularly affects the decidual spiral arteries. Reportedly, aspirin prevents preeclampsia, specifically early-onset preeclampsia, although findings in decidual arteries in women treated with aspirin therapy remain unclear. We compared the clinical and histopathological placental findings between women with a history of preeclampsia, who did and did not receive low-dose aspirin therapy (LDA and non-LDA groups, respectively). We identified 26 women with a history of preeclampsia; 9 women received LDA (aspirin ≤ 100 mg/day, initiated at < 16 weeks, LDA group), and 17 women did not receive LDA (non-LDA group). The mean gestational age was higher (36.7 weeks vs. 32.3 weeks, P = 0.0221) and the incidence of preeclampsia was lower (11% vs. 59%, P = 0.0362) in the LDA than in the non-LDA group. Histopathologically, the incidence of decidual arteriopathy, particularly that of fibrinoid necrosis and thrombosis, was lower in the LDA than in the non-LDA group (44% vs. 88%, P = 0.0283). Immunohistologically, endothelial marker (CD31 and CD39) expression was stronger in the LDA than in the non-LDA group. Notably, we observed no significant intergroup differences in inflammatory changes (chronic perivasculitis, protease-activated receptor 1 expression, and CD3-positive cells). This study highlights that LDA inhibits hypertension-induced endothelial injury and thrombosis, and thereby protects maternal placental perfusion and prevents preeclampsia.
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【徹底ガイドDICのすべて 2022-'23】病態生理と病理 病理組織
盛口 清香, 魏 峻洸
救急・集中治療 34 ( 2 ) 584 - 587 2022年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：(株)総合医学社
＜ここがポイント!＞▼播種性血管内凝固症候群(DIC)は、種々の基礎疾患によって全身の凝固線溶系が亢進した状態で、凝固系・線溶系のどちらが優位かによって、全身性に多発微小血栓が形成されることによる多臓器障害や、出血傾向をきたす病態である。▼DICの病態生理は、基礎疾患に応じて多彩で、組織所見にも多様性がある。ときに、全身の毛細血管に微小血栓が形成される。▼微小血栓は、主にフィブリンから構成され、血小板が介在する。白血球が混在する場合もある。▼剖検例の検討では、血栓形成の頻度は、主要臓器に高い傾向にある。(著者抄録)
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Tomimori K., Kodama Y., Tanaka H., Yamashita A., Gi T., Asada Y., Doi K., Katsuragi S., Sato Y.
Virchows Archiv 480 ( 6 ) 1181 - 1187 2022年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Virchows Archiv
Transient abnormal myelopoiesis (TAM), also known as transient myeloproliferative disorder or transient leukemia, is a self-regressing neoplasia that afflicts infants with trisomy 21. A recent review article documented “myeloid cell thrombus (MCT)” and “fetal vascular malperfusion (FVM)” in placentas with TAM, although the characteristic TAM placental findings have not been clarified. Here, we compared the clinical and pathological placental findings between trisomy 21 patients with or without TAM. In 13 cases of trisomy 21, we identified six placentas with TAM and seven placentas without TAM. The six placentas with TAM included two stillborn cases. Microscopically, MCT was noted in all the cases, and a high incidence of FVM (50%) was observed in TAM cases. Immunohistochemically, MCT was found to be a platelet-rich thrombus. The placentas were grouped according to the presence or absence of TAM and subsequently compared. Clinically, the incidences of abnormal fetal heart rate pattern and fetal or neonatal death were significantly higher in TAM cases. Pathologically, placenta in TAM cases weighted more than those in cases without TAM, and the incidence of MCT was significantly higher in placentas with TAM. Moreover, the incidence of FVM was higher in placentas with TAM, but this difference was not statistically significant. We propose that MCT is a diagnostic feature of placentas with TAM and may be associated with poor fetal outcomes.
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Multiple asymptomatic coronary plaque ruptures and fissures in acute myocardial infarction 査読あり 国際誌
Toshihiro Gi, Shun Nishino, Atsushi Yamashita, Nozomi Watanabe, Yoshisato Shibata, Yujiro Asada
Pathology International 72 ( 6 ) 355 - 357 2022年6月
担当区分：筆頭著者 記述言語：英語 掲載種別：症例報告
DOI： 10.1111/pin.13229
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魏 峻洸, 山下 篤, 浅田 祐士郎
医学のあゆみ 279 ( 11 ) 1084 - 1089 2021年12月
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Pericardial effusion in the course of Fabry disease cardiomyopathy: a case report. 査読あり
Tsuruda T, Higashi Y, Gi T, Nakao S
European heart journal. Case reports 5 ( 10 ) ytab407 2021年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：European Heart Journal - Case Reports
Background: Fabry disease (FD) is an X-chromosome-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. Case summary: A 51-year-old Japanese woman with a previous diagnosis of FD presented with pericardial effusion. The exudative pericardial fluid contained globotriaosylsphingosine. Left ventricular hypertrophy progressed despite regular administration of agalsidase alfa every 2 weeks over a 7-year period, with increases in plasma levels of globotriaosylsphingosine and interleukin (IL)-18. In addition, the IL-6 level in the pericardial fluid was markedly higher than that in plasma. Discussion: This case suggests that elevated IL-6 and IL-18 levels in pericardial fluid and plasma indicate the severity of FD cardiomyopathy.
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Intracellular glutamine level determines vascular smooth muscle cell-derived thrombogenicity 査読あり 国際誌
Koyama S., Yamashita A., Matsuura Y., Saito Y., Maekawa K., Gi T., Kitamura K., Asada Y.
Atherosclerosis 328 62 - 73 2021年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Atherosclerosis
Background and aims: The everolimus-eluting stent (EES), one of the effective stents for in-stent restenosis (ISR), has a lower incidence of stent thrombosis; however, the underlying mechanism remains unknown. This study aimed to identify the effects of everolimus on vascular metabolism and thrombogenicity and examine their mechanistic link. Methods: EESs and bare-metal stents were implanted in rabbit iliac arteries with smooth muscle cell (SMC)-rich neointima induced by endothelial denudation. Four weeks after stent implantation, the stented arteries were examined for histological analysis and metabolomics. Additionally, everolimus effects in coronary artery SMCs metabolism, tissue factor (TF) expression, and procoagulant activity were assessed in vitro. Results: EES-implanted arteries showed decreased neointima formation, less SMCs infiltration, and reduced TF expression. Concomitantly, they were metabolically characterized by increased levels of metabolites in amino acids, such as glutamine. Similarly, everolimus increased intracellular glutamine levels, decreased TF expression, and reduced procoagulant activity in SMCs in vitro. On the contrary, exogenous glutamine administration also increased intracellular glutamine level, decreased TF expression, and reduced procoagulant activity despite enhanced mammalian target of rapamycin (mTOR) activity. Conclusions: Intracellular glutamine level is likely to determine vascular SMC-related thrombogenicity regardless of mTOR pathway activity. Therefore, increased intracellular glutamine level might contribute partially to the beneficial effect of EES use on stent thrombosis.
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Ogawa S, Kawakami H, Suzuki S, Kuroki D, Uchiyama N, Hatada H, Gi T, Sato Y
Internal medicine (Tokyo, Japan) 60 ( 17 ) 2783 - 2791 2021年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本内科学会
Although cases of gastrointestinal toxicity of pembrolizumab have been reported, cases of acute immune-mediated colitis accompanied with metachronous esophageal disorders (esophagitis and ulcer) are rare. We herein report a case of acute colitis and metachronous esophageal ulcers due to an immune-related adverse event following concomitant pembrolizumab chemotherapy for lung adenocarcinoma. To our knowledge, there have so far been no reports of cases in which both acute immune-mediated colitis and metachronous esophageal ulcers developed. We therefore report the details of this case along with a review of the pertinent literature.
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腹部大動脈周囲リンパ節に再発した子宮頸癌が下大静脈に癌塞栓を形成した1例 査読あり
冨森 馨予, 大西 淳仁, 大澤 綾子, 圓崎 夏美, 吉本 望, 福島 和子, 川越 靖之, 中村 栄作, 中村 都英, 魏 峻洸, 佐藤 勇一郎, 鮫島 浩
宮崎県医師会医学会誌 45 ( 1 ) 39 - 43 2021年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Glioblastoma mimicking metastatic small cell carcinoma: A case report with ultrastructural findings 査読あり 国際誌
Maekawa K., Tokumitsu T., Noguchi H., Nakamura E., Gi T., Horinouchi S., Yamashita S., Takeshima H., Asada Y., Sato Y.
Diagnostic Cytopathology 49 ( 8 ) E291 - E296 2021年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Diagnostic Cytopathology
It is often straightforward to distinguish glioblastoma (GBM) from metastatic carcinoma by cytology; however, small cell variants of GBM or GBM with primitive neuronal component (GBMPNC) can mimic metastatic small cell carcinoma (SCC). Herein, we report a case of GBMPNC mimicking metastatic SCC and present cytological and ultrastructural findings. A 65-year-old man with memory disturbance was hospitalized. Magnetic resonance imaging revealed the presence of a 6 cm sized tumor in the right anterior temporal lobe. Intraoperative cytology slides indicated that the tumor consisted of small-sized cells with scant cytoplasm showing high cellularity. The initial intraoperative diagnosis was metastatic SCC; however, any primary visceral tumor was not detected clinically. Immunohistochemical and ultrastructural studies of postoperative histological sections revealed that the lesion was GBMPNC. This case shows that some GBMs may have the potential to closely mimic metastatic SCC, which expands the differential diagnosis and emphasizes the importance of clinical correlation.
DOI： 10.1002/dc.24715
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Gi T, Yamashita A, Aman M, Kuwahara A, Asada Y, Kawagoe Y, Onishi J, Sameshima H, Sato Y
Pathology international 71 ( 4 ) 261 - 266 2021年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Pathology International
Ovarian cancer is a known risk factor of venous thromboembolism (VTE). Thrombogenic factor expression and lymphocytic infiltrate have been reported in endometriosis and ovarian cancers. We reviewed 30 cases of ovarian carcinomas (high grade serous carcinoma, 10; endometrioid carcinoma, 10; clear cell carcinoma (CCC), 10) and 16 endometriotic lesions. We immunohistochemically investigated the expressions of tissue factor (TF), podoplanin, P-selectin, and number of CD4 and CD8 positive lymphocytes in cancer tissue and endometriotic lesions, along with their relationship with VTE. The expression of TF was higher in CCC. The TF expression and the number of CD8 positive cells were higher in cancer tissues with VTE than in those without VTE. The podoplanin or P-selectin expression did not differ among histological types or between cases with and without VTE. Our results demonstrated a high TF expression and intraepithelial CD8 cells in CCC, which were associated with VTE. The results suggest that infiltrating lymphocytes may affect TF expression that, in turn, influences VTE.
DOI： 10.1111/pin.13074
その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/pin.13074
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Tsuruda T., Yoshikawa N., Kai M., Yamaguchi M., Toida R., Kodama T., Kajihara K., Kawabata T., Nakamura T., Sakata K., Hatakeyama K., Gi T., Asada Y., Tono T., Kitamura K., Ikeda R.
Internal Medicine 60 ( 3 ) 423 - 429 2021年2月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Internal Medicine
We herein report the cytokine expression at different stages for three patients who developed cardiac complications after immune checkpoint inhibitor (ICI) therapy. Case 1 with biopsy-proven myocarditis showed increased levels of interleukin (IL)-8, monocyte chemotactic and activating factor, and granulocyte macrophage colony-stimulating factor (GM-CSF) when he developed Takotsubo cardiomyopathy. Case 2 with subclinical myocarditis showed predominant activation of IL-8 during the progressive clinical course. Case 3 with cytokine-releasing syndrome showed substantial activations of IL-6, IL-8, GM-CSF, and interferon-γ. Our data suggest the development of unique cytokine activation in individual patients with cardiac complications after ICI therapy.
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Setoguchi K., Yanagi S., Gi T., Tsubouchi H., Uto K., Shigekusa T., Matsumoto N., Sato Y., Nakazato M.
American Journal of Case Reports 22 ( 1 ) e932452 2021年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Case Reports
Background: Rhabdoid tumor (RT) of the lung is a rare and aggressive malignancy. The origin of and the mutation responsible for RT are entirely unknown. The distinction between RT associated with subtypes of lung cancer and SMARCA4-deficient thoracic sarcomas is also unknown. Three pulmonary subsolid nodules in the right S6, left S6, and left S8 were identified in a 78-year-old Japanese woman. At 3 and 9 months later, a chest CT showed unchanged sizes, but at 15 months the development of a 37-mm mass in the right S6 was observed. The patient’s systemic condition deteriorated rapidly, and she died 1 month later. An autopsy revealed that the mass consisted of 90% RT and 10% lung adenocarcinoma. There were another 2 adenocarcinoma lesions in the left lung. KRAS mutation analyses revealed the same KRAS mutation (G12D) in the adenocarcinoma and RT components in the identical mass and metastatic RT, indicating that all of these components had the same clonality. A different KRAS mutation in each of the 3 adenocarcino-ma lesions was detected (right S6: G12D, left S6: A59G, left S8: G12C), indicating that the multiple adenocar-cinoma lesions were truly multifocal lung adenocarcinoma. The adenocarcinoma and RT components retained SMARCA4 expression. This is the first evidence of RT originating from multifocal lung adenocarcinoma. KRAS mutation is thought to be responsible for the RT’s emergence via the epithelial-mesenchymal transition. Patients with multiple sub-solid nodules should be followed closely; aggressive surgical intervention should be considered given concerns about the evolution of this aggressive malignancy.
DOI： 10.12659/AJCR.932452
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High Signal Intensity on Diffusion-Weighted Images Reflects Acute Phase of Deep Vein Thrombus. 査読あり
Gi T, Kuroiwa Y, Yamashita A, Mizutani Y, Asanuma T, Miyati T, Maekawa K, Aman M, Imamura T, Asada Y
Thrombosis and haemostasis 2020年8月
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Signal Change of Jugular Vein Thrombus on Diffusion-Weighted Magnetic Resonance Imaging 査読あり
Kuga Naoya, Asada Yujiro, Imamura Takuroh, Kuroiwa Yasuyoshi, Sakamoto Takamichi, Yamashita Atsushi, Gi Toshihiro, Doi Shogo, Kinoshita Tomoki, Tanaka Takashi, Kihara Yasushi
Circulation Reports 2 ( 8 ) 455 - 456 2020年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本循環器学会
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Congenital Abdominal Aortic Aneurysm in a Four Year Old Girl 査読あり 国際誌
Higuchi K., Furukawa K., Nakamura E., Imamura H., Gi T., Nakamura K.
EJVES Vascular Forum 48 12 - 18 2020年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：EJVES Vascular Forum
© 2020 The Author(s) Introduction: Abdominal aortic aneurysm (AAA) in neonates, infants, and children is uncommon, usually occurring as a result of infections, connective tissue disorders, vasculitis, or iatrogenic trauma. A case of idiopathic congenital AAA, an extremely rare disease of unknown origin, is described. Report: In March 2018, a 40 mm hypoechoic mass adjacent to the left kidney was detected incidentally by abdominal ultrasound for investigation of hypercalciuria in a four year old girl. Contrast enhanced computed tomography (CT) revealed an infrarenal fusiform AAA measuring 39 mm in maximum diameter, a 15 mm left renal artery aneurysm, a 14 mm right hypogastric artery aneurysm, and a 12 mm left hypogastric artery aneurysm. Cerebral magnetic resonance imaging revealed multiple intracranial aneurysms between 8 and 15 mm in diameter. Considering the size of the AAA and risk of rupture, surgical repair was planned. In May 2018, the congenital AAA was successfully repaired with a 10 mm Dacron aorto-aortic tube graft. Increases in the size of the left renal artery aneurysm and a left middle meningeal artery aneurysm were detected 12 and 14 months post-operatively, respectively. Coil embolisations were performed. An intracranial dural arteriovenous fistula (AVF) was discovered incidentally by cerebral angiography for treatment of the left middle meningeal artery aneurysm. Transarterial embolisation for AVF was also performed. At the 21 month post-operative follow up, the patient is doing well, and the untreated aneurysms have not grown. Conclusion: Long term outcomes after surgical repair for congenital AAA are unclear. Moreover, growth of residual aneurysms was detected post-operatively, so follow up with frequent multimodality imaging for multiple aneurysms is necessary.
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Yamashita A., Nishihira K., Gi T., Maekawa K., Hatakeyama K., Horiuchi S., Wada K., Shibata Y., Asada Y.
Thrombosis and Haemostasis 121 ( 2 ) 234 - 241 2020年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis and Haemostasis
© 2020 Georg Thieme Verlag KG Stuttgart New York. Arterial thrombus formation is thought to be initiated by platelet adhesion to the subendothelial matrix, but ruptured atherosclerotic plaques are characterized by substantial reduction of matrix proteins compared with stable plaques. Intraplaque erythrocytes and/or fibrin have been reported in high-risk coronary plaques. The aims of the current study were to identify factors that provide scaffolds for platelets at the sites of ruptured coronary plaques and investigate depositions of iron and bilirubin as hemoglobin catabolites in the ruptured plaques. Histological characteristics of plaque components and the thrombus interface were examined in 73 acute coronary aspirated thrombi. Necrotic debris (95%), macrophages (95%), and cholesterin clefts (81%) were observed frequently at the ruptured plaque and thrombus interface. A fibrous matrix (47%), calcification (32%), and extracellular deoxyribonucleic acid (15%) were identified as small foci. Tissue factor was localized in the necrotic core and macrophages. Fibrin and von Willebrand factor were consistently deposited within the plaques and beneath platelet aggregations. The citrullinated histone H3-immunopositive area accounted for only 0.5% of the plaque area. Bilirubin and iron depositions were detected in approximately 20% of the plaques in addition to biliverdin reductase and ferritin expression in macrophages. Fibrin and von Willebrand factor rather than matrix proteins and neutrophil extracellular traps may be major adhesive molecules at the sites of ruptured plaques. Iron and bilirubin deposits may be markers for rupture-prone plaques.
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Nishino S., Watanabe N., Gi T., Kuriyama N., Shibata Y., Asada Y.
Circulation: Cardiovascular Imaging 13 ( 12 ) e011396 2020年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation: Cardiovascular Imaging
© 2020 Georg Thieme Verlag. All rights reserved. Background: Recent animal studies have suggested that mitral valve (MV) leaflet remodeling can occur even without significant tethering force and that the postinfarct biological reaction would contribute to the histopathologic changes of the leaflet. We serially evaluated the MV remodeling in patients with anterior and inferior acute myocardial infarction (MI), by using 2-And 3-dimensional transthoracic echocardiography. Additional histopathologic examinations were performed to assess the leaflet pathology. Methods: Sixty consecutive first-onset acute MI (anterior MI, n=30; inferior MI, n=30) patients who underwent successful primary percutaneous coronary intervention were examined (1) before primary percutaneous coronary intervention, (2) at 6-month follow-up, and (3) at follow-up 1 year or later after onset. MV complex geometry including MV leaflet area and thickness was analyzed using dedicated software. Additional histopathologic study compared 18 valves harvested during surgery for ischemic mitral regurgitation (MR). Results: MV area and thickness incrementally increased during the follow-up period. MV leaflet area significantly increased (anterior MI: 5.59 [5.28-5.98] to 6.54 [6.20-7.26] cm2/m2, P<0.001; inferior MI: 5.60 [4.76-6.08] to 6.32 [5.90-6.90] cm2/m2, P<0.001), and leaflet thickness also increased (anterior MI: 1.09 [0.92-1.24] to 1.45 [1.28-1.60] mm/m2, P<0.001; inferior MI: 1.15 [1.03-1.25] to 1.44 [1.27-1.59] mm/m2, P<0.001); data represent onset versus ≥1 year. Larger annuls, larger tenting, and a reduced leaflet area/annular ratio with smaller coaptation index were observed in patients with persistent ischemic MR compared with those without significant ischemic MR. Histopathologic examinations revealed that MV thickness was significantly greater in chronic ischemic MR compared with acute ischemic MR (1432.6±490.5 versus 628.7±278.7 μm; P=0.001), with increased smooth muscle cells and fibrotic materials. Conclusions: MV leaflet remodeling progressed both in area and thickness after MI. This is the first clinical study to record the longitudinal course of MV leaflet remodeling by serial echocardiography.
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Kuroiwa Y., Uchida A., Yamashita A., Miyati T., Maekawa K., Gi T., Noguchi T., Yasuda S., Imamura T., Asada Y.
Cardiovascular Pathology 40 24 - 31 2019年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cardiovascular Pathology
© 2019 Elsevier Inc. Coronary high-signal-intensity plaques (HIPs) detected by T 1 -weighted magnetic resonance imaging are associated with future cardiovascular events. This study aimed to identify pathological findings reflecting HIPs in coronary arteries obtained from autopsy cases. Formalin-fixed hearts were imaged with noncontrast T 1 -weighted imaging with a 1.5-T magnetic resonance system. We defined HIPs or non-HIPs as a coronary plaque to myocardial signal intensity ratio (PMR) of ≥1.4 or <1.4, respectively. We found HIPs in 4 of 37 (10.8%) hearts and analyzed 7 hearts in detail. The corresponding sections to HIPs (n=11) or non-HIPs (n=25) were histologically and immunohistochemically analyzed. We calculated the T 1 relaxation time of human venous blood in vitro. Plaque and necrotic core areas, and the frequency of intraplaque hemorrhage in HIPs were significantly larger/higher than those in non-HIPs. HIPs were immunopositive for CD68 (11/11), glycophorin A (10/11), and fibrin (11/11). Glycophorin-A-, matrix metalloprotease 9 (MMP9)-, and tissue factor-immunopositive areas were larger in HIPs than in non-HIPs. The PMR was positively correlated with glycophorin-A-, fibrin-, MMP9-, and tissue factor-immunopositive areas. Blood coagulation shortened the T 1 relaxation time of the blood and plasma, and the T 1 relaxation times in coagulated whole blood and erythrocyte-rich blood were significantly shorter than those in plasma. Coronary HIPs may reflect intraplaque hemorrhage and may be a novel marker for plaque instability and thrombogenic potential.
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Maekawa K., Sugita C., Yamashita A., Moriguchi-Goto S., Furukoji E., Sakae T., Gi T., Hirai T., Asada Y.
Thrombosis Research 177 136 - 144 2019年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Research
© 2019 Elsevier Ltd Background: Thrombolytic therapy is effective in fresh deep vein thrombosis (DVT) although the benefit may fall below the risk of bleeding in non-fresh thrombosis. Markers reflecting fresh DVT have not been established. The present study aims to identify metabolites reflecting fresh venous thrombus and their role in thrombus formation. Methods: Metabolites of rabbit venous blood and jugular venous thrombus 4 h after thrombus induction were analysed using electrophoresis-time of flight mass spectrometry. The effects of the altered metabolites on blood coagulation and platelet aggregation were assessed by using rotation thromboelastometry and platelet aggregometer. Cellular contents and glucose transporter (Glut)-1 expression in aspirated human DVT samples were pathologically analysed. Results: Metabolome analysis identified 226 metabolites (133 cationic and 93 anionic metabolites). Largely altered 18 metabolites (thrombus/blood ratio: >5 or <0.5) included glycolytic metabolites, redox-related metabolites, purine nucleotides and tryptophan metabolites. Among the metabolites with >5-fold increase, lactic acid was most abundant and guanine modestly enhanced whole blood clotting with thromboelastometry. Lactic acid and adenosine monophosphate inhibited collagen-induced platelet aggregation. Human DVTs were rich in erythrocytes expressing Glut-1. The erythrocyte content and Glut-1 expression were negatively correlated with the time after onset of DVT. Conclusions: Glycolysis-, purine-, and redox-related metabolites may reflect fresh erythrocyte-rich venous thrombus, and altered metabolites may affect venous thrombus formation. An increased level of lactate may reflect active glycolysis of thrombus cellular components, predominantly erythrocytes.
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A Case of Malignant Transformation of Epidermoid Cyst with Cerebrospinal Fluid Dissemination 査読あり
Suematsu Y, Takeishi G, Yokogami K, Uehara H, Gi T, Yamashita A, Sato Y, Takeshima H
No Shinkei Geka 46 ( 6 ) 509 - 514 2018年6月
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Nakamura E, Sato Y, Iwakiri T, Yamashita A, Moriguchi-Goto S, Maekawa K, Gi T, Asada Y
Journal of atherosclerosis and thrombosis 2017年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本動脈硬化学会
<b><i>Aim</i></b>: Patients with peripheral artery disease (PAD) have a high prevalence of cardiovascular morbidity and mortality; however, majority of patients with PAD are asymptomatic. This study aimed to histologically evaluate whether asymptomatic, lower extremity artery plaques are associated with systemic atherosclerosis and the onset of cardiovascular disease (CVD) events using autopsy cases.<b><i>Methods</i></b>: We histologically investigated the atherosclerotic plaques of the common iliac, common carotid, coronary, and renal arteries from 121 autopsy cases without symptoms of PAD (mean age:67.6 years; 63% men; 83% non-CVD death). We evaluated the relationship between the degree of iliac artery atherosclerosis and that of other arteries, and also the presence of any CVD, myocardial infarction, stroke, and renal failure.<b><i>Results</i></b>: Advanced atherosclerotic plaques (American Heart Association ≥4) were present in 86 (72%) common iliac arteries in these cases. These arteries also showed high frequencies of calcification (66%), intraplaque hemorrhage (42%), and plaque disruption (24%). These advanced lesions were associated with age (≥60 years), sex (male), hypertension, diabetes, and smoking habit (all <i>P</i><b>＜</b>0.05). Additionally, it was significantly associated with CVD (odds ratio, 95% confidence interval; 6.2, 2.2–22), myocardial infarction (6.4, 1.2–19), stroke (8.7, 1.7–16), and renal failure/hemodialysis (5.8, 1.1–11). Cases with advanced iliac artery plaques had advanced coronary and carotid atherosclerosis.<b><i>Conclusion</i></b>: These results indicate that asymptomatic advanced plaques are frequently observed in common iliac arteries, and are associated with generalized atherosclerosis and CVD events.
DOI： 10.5551/jat.39669
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傍糸球体細胞腫の1例 査読あり
中村 恵理子, 山下 篤, 魏 峻洸, 前川 和也, 盛口 清香, 佐藤 勇一郎, 北 俊弘, 佐藤 俊介, 浅田 祐士郎
診断病理 34 ( 3 ) 247 - 251 2017年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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子宮体下部(峡部)に発生した類内膜腺癌の1例 査読あり
佐藤勇一郎, 盛口清香, 山下篤, 前川和也, 中村恵理子, 魏峻洸, 福島和子、大西淳仁, 川越靖之, 鮫島浩, 浅田祐士郎
日本婦人科病理学会誌 2017年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Microvascular proliferation of brain metastases mimics glioblastomas in squash cytology 査読あり
Gi T., Sato Y., Tokumitsu T., Yamashita A., Moriguchi-Goto S., Takeshima H., Sato S., Asada Y.
Cytopathology 28 ( 3 ) 228 - 234 2017年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Cytopathology
© 2016 John Wiley & Sons Ltd Objective: Although microvascular proliferation is a key feature in the diagnosis of high-grade glioma, the characteristics of metastatic tumour vessels in smear preparations have not been documented. In this study, the vascular changes in metastatic brain tumours, using squash cytology to examine the vascular patterns in brain metastases, were reviewed. Methods: One hundred and forty-three squash smears of brain tissue, including 25 normal or reactive tissue, 23 malignant lymphomas, 8 grade I glioma (pilocytic astrocytoma), 23 grade II glioma (diffuse astrocytoma and oligodendroglioma), 42 grade IV glioma (glioblastoma), and 22 metastasis, were assessed. Two vascular patterns were assessed: thick and branching, and glomeruloid. The vessel density, nuclear layer and the number of vessel branches were compared. Furthermore, tumour vessels of brain metastases were analysed by histology and for immunohistochemical expression of CD34, α-smooth muscle actin (SMA) and high-molecular-weight caldesmon (h-CD). Results: Among 22 metastatic tumours, thick and branching vessels were found in 17 (77%) and glomeruloid vessels in 13 (59%). These incidences of microvascular proliferation patterns were similar to those of glioblastomas or pilocytic astrocytomas. Vessel density, nuclear layer and vessel wall branches were significantly higher in metastatic tumours than malignant lymphomas, grade II gliomas or normal brain tissues. Glomeruloid vessels consisted of CD34-positive cells and α-SMA-positive cells, and α-SMA-positive cells had a low h-CD expression. These immunohistochemical patterns were similar to those of high-grade gliomas. Conclusions: The vascular features of metastatic brain tumours are similar to those of glioblastomas, suggesting that these microvascular proliferations contribute to the progression of metastatic tumours.
DOI： 10.1111/cyt.12405
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Hida R., Yamamoto H., Hirahashi M., Kumagai R., Nishiyama K., Gi T., Esaki M., Kitazono T., Oda Y.
American Journal of Surgical Pathology 41 ( 3 ) 343 - 353 2017年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Surgical Pathology
© 2016 Wolters Kluwer Health, Inc. All rights reserved. Duodenal neoplasm of gastric phenotype (DNGP) is very rare, and details of its histopathologic, genetic, and biological features are still unclear. Frequent gene mutations in GNAS, KRAS, and APC have been reported in pyloric gland adenomas and fundic gland-type neoplasms (initially reported as low-grade adenocarcinomas) of the stomach. Here we retrospectively analyzed 16 cases of extra-ampullary DNGP (benign to malignant), and we examined the mucin immunoprofile and oncogene mutations (GNAS, KRAS, APC, BRAF, and CTNNB1). The 16 DNGPs were histologically classified into adenomas (5 pyloric gland adenomas and 2 foveolar-type adenomas), neoplasms of uncertain malignant potential (NUMPs, n=6), and invasive adenocarcinomas (n=3). NUMPs consisted of slightly atypical epithelial cells with pale, eosinophilic, or basophilic cytoplasm growing in an anastomosing or branching glandular pattern, often with expansive submucosal extension. In contrast to invasive adenocarcinomas, NUMPs lacked significant nuclear irregularity, desmoplastic stromal reaction, lymphovascular invasion, and metastasis; their features were reminiscent of fundic gland-type neoplasms of the stomach. Immunophenotypically, most of NUMPs were predominantly positive for MUC6 with variable expressions of pepsinogen-I, H + K + ATPase, human gastric mucin, and MUC5AC. Molecular analyses reve aled the gene mutations of GNAS in 6 (38%) of 16 DNGPs (4 [57%] adenomas, 1 [16%] NUMP, and 1 [33%] invasive adenocarcinoma) and APC in 4 of 15 (27%) DNGPs: no adenomas, 2 (33%) NUMPs, and 2 (67%) invasive adenocarcinomas. BRAF mutation was present in only 1 (16%) NUMP, and KRAS and CTNNB1 mutations were absent. In conclusion, gastric-phenotype adenomas and NUMPs of the duodenum are similar to their counterparts of the stomach, in terms of histologic, genetic, and clinicopathologic features. We propose the term "NUMP" as an intermediate category between adenoma and definitely invasive adenocarcinoma. Our findings may provide novel insights into the classification of undescribed but distinctive duodenal tumors showing similarity to gastric-phenotype neoplasms of the stomach.
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Furukoji E., Gi T., Yamashita A., Moriguchi-Goto S., Kojima M., Sugita C., Sakae T., Sato Y., Hirai T., Asada Y.
Thrombosis Journal 14 ( 1 ) 46 2016年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Journal
© 2016 The Author(s). Background: Thrombolytic therapy is effective in selected patients with deep vein thrombosis (DVT). Therefore, identification of a marker that reflects the age of thrombus is of particular concern. This pilot study aimed to identify a marker that reflects the time after onset in human aspirated DVT. Methods: We histologically and immunohistochemically analyzed 16 aspirated thrombi. The times from onset to aspiration ranged from 5 to 60days (median of 13days). Paraffin sections were stained with hematoxylin and eosin and antibodies for fibrin, glycophorin A, integrin α2bβ3, macrophage markers (CD68, CD163, and CD206), CD34, and smooth muscle actin (SMA). Results: All thrombi were immunopositive for glycophorin A, fibrin, integrin α2bβ3, CD68, CD163, and CD206, and contained granulocytes. Almost all of the thrombi had small foci of CD34- or SMA-immunopositive areas. CD68- and CD163-immunopositive cell numbers were positively correlated with the time after onset, while the glycophorin A-immunopositive area was negatively correlated with the time after onset. In double immunohistochemistry, CD163-positive cells existed predominantly among the CD68-immunopositive macrophage population. CD163-positive macrophages were closely localized with glycophorin A, CD34, or SMA-positive cell-rich areas. Conclusions: These findings indicate that CD163 macrophage and erythrocyte contents could be markers for evaluation of the age of thrombus in DVT. Additionally, CD163 macrophages might play a role in organization of the process of venous thrombus.
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悪性度の診断に苦慮した悪性Brenner腫瘍の1例. 査読あり
魏 峻洸, 佐藤勇一郎, 村岡純輔, 福島和子, 川越靖之, 鮫島浩, 浅田祐士郎
日本婦人科病理学会誌 7 ( 1 ) 17 - 19 2016年
記述言語：日本語 掲載種別：研究論文（学術雑誌）