Ueno, Akihisa

写真a

Affiliation

School of Medicine, Division of Diagnostic Pathology (Shinanomachi)

Position

Instructor

Career 【 Display / hide

  • 2000.05
    -
    2002.04

    Keio University School of Medicine, Department of Radiology, Resident(Course)

  • 2002.05
    -
    2003.06

    Keio University School of Medicine, Department of Radiology, Postgraduate Training Course

  • 2003.07
    -
    2005.06

    Nippon Koukan Hospital, Department of Radiolgy, Doctor

  • 2005.07
    -
    2006.04

    Keio University School of Medicine, Department of Radiology, Postgraduate Training Course

  • 2006.05
    -
    2010.03

    Keio University School of Medicine, Department ofRadiology, Assistant

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Academic Background 【 Display / hide

  • 1993.04
    -
    2000.03

    Chiba University, 医学部

    University, Graduated

  • 2010.04
    -
    2014.03

    Keio University, 医学研究科, 医学研究系

    Graduate School, Withdrawal after completion of doctoral course requirements, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, Coursework, 2015.01

    OATP1B3 expression is strongly associated with Wnt/β-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma.

Licenses and Qualifications 【 Display / hide

  • Medical licence, 2000.06

  • 放射線診断専門医, 2005.10

  • 病理専門医, 2020.09

 

Research Areas 【 Display / hide

  • Life Science / Human pathology

  • Life Science / Experimental pathology

  • Life Science / Radiological sciences

Research Keywords 【 Display / hide

  • Hepatocellular carcinoma

Research Themes 【 Display / hide

  • 肝細胞癌の画像病理対比, 

    2009.04
    -
    Present

 

Books 【 Display / hide

  • 腫瘍病理鑑別診断アトラス 肝癌 第2版

    波多野まみ, 尾島英知, 上野彰久, 坂元亨宇, 文光堂, 2020.11,  Page: 313

    Scope: 第2部 組織型と診断の実際 I. 肝細胞系腫瘍 4.肝細胞癌の組織亜型,  Contact page: 54-62

  • 腹部のCT 第3版

    上野彰久 佐藤浩三 松坂陽至 上野彰久, メディカルサイエンス・インターナショナル, 2017.04

    Scope: III. 肝臓 IV.胆嚢・胆管

  • EOB-MRI/Sonazoid超音波による肝癌の診断と治療

    上野彰久 坂元亨宇, 医学書院, 2013.06

    Scope: 第7章 EOB-MRIの早期歓談と異型結節(DN)の鑑別診断能  1. 早期肝癌の病理診断 1分子病理

  • 腹部のCT 第2版

    上野彰久 倉田忠宜, メディカルサイエンス・インターナショナル, 2010.04

    Scope: V. 胆嚢・胆管

Papers 【 Display / hide

  • Immunovascular classification of HCC reflects reciprocal interaction between immune and angiogenic tumor microenvironments

    Kurebayashi Y., Matsuda K., Ueno A., Tsujikawa H., Yamazaki K., Masugi Y., Kwa W.T., Effendi K., Hasegawa Y., Yagi H., Abe Y., Kitago M., Ojima H., Sakamoto M.

    Hepatology (Hepatology)   2021

    ISSN  02709139

     View Summary

    Background and Aims: Immune cells and tumor vessels constitute important elements in tumor tissue; however, their detailed relationship in human tumors, including HCC, is still largely unknown. Consequently, we expanded our previous study on the immune microenvironment of HCC and analyzed the relationship among the immune microenvironment, inflammatory/angiostatic factor expression, angiogenic factor expression, and tumor vessel findings, including vessels encapsulating tumor clusters (VETC) and macrotrabecular-massive (MTM) patterns. Approach and Results: We classified HCC into four distinct immunovascular subtypes (immune-high/angiostatic [IH/AS], immune-mid/angio-mid [IM/AM], immune-low/angiogenic [IL/AG], and immune-low/angio-low [IL/AL]). IH/AS, IM/AM, and IL/AG subtypes were associated with decreasing lymphocytic infiltration and increasing angiogenic factor expression and VETC/MTM positivity, reflecting their reciprocal interaction in the tumor microenvironment of HCC. IL/AG subtype was further characterized by CTNNB1 mutation and activation of Wnt/β-catenin pathway. IL/AL subtype was not associated with increased lymphocyte infiltration or angiogenic factor expression. Prognostically, IH/AS subtype and VETC/MTM positivity were independently significant in two independent cohorts. Increased angiogenic factor expression was not necessarily associated with VETC/MTM positivity and poor prognosis, especially when inflammatory/angiostatic milieu coexisted around tumor vessels. These results may provide insights on the therapeutic effects of immunotherapy, antiangiogenic therapies, and their combinations. The potential of evaluating the immunovascular microenvironment in predicting the clinical effect of these therapies in nonresectable HCC needs to be analyzed in the future study. Conclusions: HCC can be classified into four distinct immunovascular subtypes (IH/AS, IM/AM, IL/AG, and IL/AL) that reflect the reciprocal interaction between the antitumor immune microenvironment and tumor angiogenesis. In addition to its clinicopathological significance, immunovascular classification may also provide pathological insights on the therapeutic effect of immunotherapy, antiangiogenic therapy, and their combination.

  • Three distinct stroma types in human pancreatic cancer identified by image analysis of fibroblast subpopulations and collagen

    Ogawa, Y., Masugi, Y., Abe, T., Yamazaki, K., Ueno, A., Fujii-Nishimura, Y., Hori, S., Yagi, H., Abe, Y., Kitago, M. and Sakamoto, M.

    Clin Cancer Res (Clinical Cancer Research)  27 ( 1 ) 107 - 119 2020.10

    ISSN  1078-0432

     View Summary

    PURPOSE: Cancer-associated fibroblasts have emerged to be highly heterogenous and can play multifaced roles in dictating pancreatic ductal adenocarcinoma (PDAC) progression, immunosuppression and therapeutic response, highlighting the need for a deeper understanding of stromal heterogeneity between patients and even within a single tumor. We hypothesized that image analysis of fibroblast subpopulations and collagen in PDAC tissues might guide stroma-based patient stratification to predict clinical outcomes and tumor characteristics. EXPERIMENTAL DESIGN: A novel multiplex immunohistochemistry-based image analysis system was established to digitally differentiate fibroblast subpopulations. Using whole-tissue slides from 215 treatment-naive PDACs, we performed concurrent quantification of principal fibroblast subpopulations and collagen and defined three stroma types: collagen-rich stroma, fibroblast activation protein a (FAP)-dominant fibroblast-rich stroma and a smooth muscle actin (ACTA2)-dominant fibroblast-rich stroma. These stroma types were assessed for the associations with cancer-specific survival by multivariable Cox regression analyses, and with clinicopathological factors including CD8(+) cell density. RESULTS: FAP-dominant fibroblasts and ACTA2-dominant fibroblasts represented the principal distinct fibroblast subpopulations in tumor stroma. Stroma types were associated with patient survival, SMAD4 status and transcriptome signatures. Compared with FAP-dominant fibroblast-rich stroma, collagen-rich stroma correlated with prolonged survival (HR, 0.57; 95% CI, 0.33-0.99), while ACTA2-dominant fibroblast-rich stroma exhibited poorer prognosis (HR, 1.65; 95% CI, 1.06-2.58). FAP-dominant fibroblast-rich stroma was additionally characterized by restricted CD8(+)-cell infiltrates and intense neutrophil infiltration. CONCLUSIONS: This study identified three distinct stroma types differentially associated with survival, immunity and molecular features, thereby underscoring the importance of stromal heterogeneity in subtyping pancreatic cancers and supporting the development of anti-stromal therapies.

  • Telomerase reverse transcriptase (TERT) promoter mutation correlated with intratumoral heterogeneity in hepatocellular carcinoma

    Kwa, W. T., Effendi, K., Yamazaki, K., Kubota, N., Hatano, M., Ueno, A., Masugi, Y. and Sakamoto, M.

    Pathol Int (Pathology International)  70 ( 9 ) 624 - 632 2020.09

    ISSN  13205463

     View Summary

    Telomerase reverse transcriptase (TERT) promoter mutations are frequently observed in hepatocellular carcinoma (HCC); however, the impact of TERT promoter mutations (TPMs) on clinical features and morphological patterns in HCC remains unresolved. Using DNA extracted from 97 HCCs, correlations between TPM status and both the clinical features of HCC and the immunohistochemically-based subgroups were evaluated. Morphological tumor patterns were semi-quantitatively analyzed using hematoxylin and eosin-stained slides of the whole tumor cross-sectional area. The percentages of tumor area occupied by early, well, moderate and poor histological patterns were calculated as a homogeneity index. TPMs were observed in 53 of 97 (55%) HCCs and were significantly associated with older age (P = 0.018) and HCV-related background (P = 0.048). The biliary/stem cell marker-positive subgroup was less likely to have TPMs (29%) compared to the Wnt/beta-catenin signaling marker-positive subgroup (60%). In contrast to TPM-negative HCCs, TPM-positive HCCs clearly exhibited intratumoral morphological heterogeneity (0.800 +/- 0.117 vs 0.927 +/- 0.096, P < 0.0001), characterized by two or more heterogeneous histological patterns (P < 0.0001) and had more well or early differentiated histological patterns (P = 0.024). Our findings showed that intratumoral heterogeneity was strongly related to TPM-positive HCCs, which established novel roles of TPMs, and may improve our understanding particularly about HCC development and diagnosis.

  • Incidentally detected microcystic serous cystadenoma of the pancreas with splenic invasion: a case report and literature review

    Yagi, F., Akita, H., Ueno, A., Takano, K., Masugi, Y., Sakamoto, M., Kitago, M., Shinoda, M., Kitagawa, Y., Toyama, K., Matsusaka, Y., Yashiro, H., Okuda, S. and Jinzaki, M.

    BJR Case Rep 6 ( 2 ) 20190109 2020.09

    ISSN  2055-7159

     View Summary

    Serous cystic neoplasms are relatively uncommon and rarely possess malignant potential. We report a rare case of pancreatic serous cystadenoma with splenic invasion in a female in her 60s. Dynamic contrast-enhanced CT revealed a 3 cm mass in the tail of the pancreas. The lesion showed marked enhancement in the arterial phase on dynamic CT, which extended into the spleen. No cystic components were detected in the pancreatic mass on either magnetic resonance cholangiopancreatography or T 2 weighted imaging. No metastasis or lymph node swelling was detected. Based on the hypervascularity of the tumour, the pre-operative diagnosis was pancreatic neuroendocrine tumour with splenic invasion. The patient underwent laparoscopic distal pancreatectomy with splenectomy. The pathological diagnosis was microcystic serous cystadenoma with locally aggressive features (infiltration into spleen, lymph nodes, and splenic vein). A few cases of pancreatic serous cystadenomas with splenic invasion have been reported; all were symptomatic, with diameters greater than approximately 9 cm. This is the first known case of incidentally detected serous cystadenoma with splenic invasion, reported with detailed imaging findings of dynamic CT and MRI.

  • Quantification of intratumoral collagen and elastin fibers within hepatocellular carcinoma tissues finds correlations with clinico-patho-radiological features

    Maehara, J., Masugi, Y., Abe, T., Tsujikawa, H., Kurebayashi, Y., Ueno, A., Ojima, H., Okuda, S., Jinzaki, M., Shinoda, M., Kitagawa, Y., Oda, Y., Honda, H. and Sakamoto, M.

    Hepatol Res (Hepatology Research)  50 ( 5 ) 607 - 619 2020.05

    ISSN  13866346

     View Summary

    AIM: Emerging evidence suggests a promising role for tumor stromal factors in characterizing patients with various types of malignancies, including hepatocellular carcinoma (HCC). We quantified the amount of collagen and elastin fibers in HCC samples with the aim of clarifying the clinico-patho-radiological significance of fiber deposition in HCC. METHODS: We computed the amount of collagen and elastin fibers using digital image analysis of whole-slide images of Elastica van Gieson-stained tissues from 156 surgically resected HCCs. Furthermore, we assessed the correlations between the fiber content of HCC samples and clinical, pathological, and radiological features, including immunohistochemistry-based molecular subtypes and immunosubtypes. RESULTS: The intratumoral area ratio of collagen in HCC tissues (median 3.4%, range 0.1-22.2%) was more than threefold that of elastin (median 0.9%, range 0.1-9.0%); there was a strong positive correlation between the amounts of collagen and elastin. Higher levels of combined collagen and elastin were significantly associated with the confluent multinodular macroscopic tumor type, the absence of a fibrous capsule, intratumoral steatosis, scirrhous tumor stroma, dense inflammatory-cell infiltrates, and the biliary/stem cell markers-positive HCC subtype. The associations of higher collagen levels with radiological findings, including heterogeneous enhancement and persistent enhancement on dynamic computed tomography, were significant. In contrast, the associations of radiological findings with elastin fibers were not significant. Intratumoral fibrous stroma in HCC comprised septum-like and perisinusoidal fibrosis; these two forms represented distinct distribution patterns of fibers and fibroblasts. CONCLUSION: Quantitative analysis suggested that stromal fiber-rich HCCs likely represent a distinct clinico-patho-radiological entity.

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Reviews, Commentaries, etc. 【 Display / hide

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Presentations 【 Display / hide

  • 胆嚢原発の脱分化型脂肪肉腫の一例

    上野彰久 尾島英知 眞杉洋平 大島剛 紅林泰 久保田直人 阿部雄太 北川雄光 大喜多肇 坂元亨宇

    第107回日本病理学会総会, 

    2018.06

    Poster presentation

  • EOB-MRIによるWnt/β-catenin activated subtype HCCの検出能に関する検討

    上野彰久 真杉洋平 山崎剣 Effendi Kathryn 辻川華子 谷本伸弘 奥田茂男 板野理 北川雄光 陣崎雅弘 坂元亨宇

    第11回 日本肝がん分子標的治療研究会, 

    2015.01

    Poster presentation

  • 胆管疾患up-to-date 画像

    UENO AKIHISA

    第33回 画像医学会, 

    2014.02

    Public lecture, seminar, tutorial, course, or other speech

  • 肝細胞癌におけるGd-EOB-DTPAのトランスポーターの網羅的解析

    上野彰久 谷本伸弘 坂元亨宇

    第39回 肝臓学会東部会, 

    2012.12

    Symposium, workshop panel (public)

  • Reduction of Blooming Artifact of Calcification with Prototype Fine-Cell Detector Computed Tomography (0.3mm collimation): Comparison with 64-Slice MDCT

    Tanami, Yutaka, Jinzaki, Masahiro, Sato, Kozo, Ueno, Akihisa, Yamada, Minoru, Kuribayashi, Sachio

    CIRCULATION, 

    2008.10

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • Elucidating the mechanism of tumor thrombotic vascular invasion in hepatocellular carcinoma

    2021.04
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

Awards 【 Display / hide

  • MOST VIEWS JRS ELECTRONIC EXHIBIT DURING ARRS 2015 ANUAL MEETING

    2015.06, American Roentgen Ray Society, OATP1B3 expression is strongly associated with Wnt/β-catenin signaling and represents the transporter of Gd-EOB-DTPA in hepatocellular carcinoma

    Country: United States

  • Cypos Gold Medal

    2014.04, 日本医学放射線学会, OATP1B3 expression is strongly associated with Wnt/β-catenin signaling and represents the transporter of Gd-EOB-DTPA in hepatocellular carcinoma

  • 板井悠二賞

    2010.01, 肝血流動態イメージ研究会, EOBプリモビスト造影MRIの肝細胞相で低信号を呈する乏血性結節の転帰に関する検討

 

Courses Taught 【 Display / hide

  • GENERAL PATHOLOGY

    2021

  • GENERAL PATHOLOGY

    2020

  • 病理学各論

    2020, Laboratory work/practical work/exercise, Within own faculty

Courses Previously Taught 【 Display / hide

  • 病理学各論

    Keio University

    2018.04
    -
    2019.03

    Full academic year, Laboratory work/practical work/exercise

  • 病理学総論

    Keio University

    2018.04
    -
    2019.03

    Full academic year, Laboratory work/practical work/exercise

 

Memberships in Academic Societies 【 Display / hide

  • 日本臨床細胞学会, 

    2017.04
    -
    Present
  • 日本病理学会, 

    2015.10
    -
    Present
  • 日本肝臓学会, 

    2012.12
    -
    Present
  • 日本癌学会, 

    2010.04
    -
    Present
  • 日本医学放射線学会, 

    2000.04
    -
    Present