Hashiguchi, Akinori

写真a

Affiliation

School of Medicine, Electron Microscope Laboratory (Shinanomachi)

Position

Assistant Professor/Senior Assistant Professor

External Links

Career 【 Display / hide

  • 1995.04
    -
    1997.03

    慶應義塾大学医学部, 病理学教室, 慶應義塾大学医学部助手(病理学)

  • 1997.04
    -
    2007.03

    慶應義塾大学医学部, 病理学教室, 慶應義塾大学助手(医学部病理学)

  • 2007.04
    -
    2013.11

    慶應義塾大学医学部, 病理学教室, 慶應義塾大学助教(医学部病理学)

  • 2013.12
    -
    Present

    慶應義塾大学医学部, 病理学教室, 慶應義塾大学専任講師(医学部病理学)

Academic Background 【 Display / hide

  • 1989.04
    -
    1995.03

    Keio University, School of Meicine

    Japan, University, Graduated

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, Dissertation, 2010.11

    Using immunofluorescent digital slide technology to quantify protein expression in archival paraffin-embedded tissue sections

 

Research Areas 【 Display / hide

  • Human pathology

Research Keywords 【 Display / hide

  • Digital Pathology

  • Renal Pathology

 

Papers 【 Display / hide

  • Association of glomerular DNA damage and DNA methylation with one-year eGFR decline in IgA nephropathy

    Hayashi K., Hishikawa A., Hashiguchi A., Azegami T., Yoshimoto N., Nakamichi R., Tokuyama H., Itoh H.

    Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

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    © 2020, The Author(s). Accumulation of DNA double-strand breaks (DSBs) is linked to aging and age-related diseases. We recently reported the possible association of DNA DSBs with altered DNA methylation in murine models of kidney disease. However, DSBs and DNA methylation in human kidneys was not adequately investigated. This study was a cross-sectional observational study to evaluate the glomerular DNA DSB marker γH2AX and phosphorylated Ataxia Telangiectasia Mutated (pATM), and the DNA methylation marker 5-methyl cytosine (5mC) by immunostaining, and investigated the association with pathological features and clinical parameters in 29 patients with IgA nephropathy. To evaluate podocyte DSBs, quantitative long-distance PCR of the nephrin gene using laser-microdissected glomerular samples and immunofluorescent double-staining with WT1 and γH2AX were performed. Glomerular γH2AX level was associated with glomerular DNA methylation level in IgA nephropathy. Podocytopathic features were associated with increased number of WT1(+)γH2AX(+) cells and reduced amount of PCR product of the nephrin gene, which indicate podocyte DNA DSBs. Glomerular γH2AX and 5mC levels were significantly associated with the slope of eGFR decline over one year in IgA nephropathy patients using multiple regression analysis adjusted for age, baseline eGFR, amount of proteinuria at biopsy and immunosuppressive therapy after biopsy. Glomerular γH2AX level was associated with DNA methylation level, both of which may be a good predictor of renal outcome in IgA nephropathy.

  • Evaluation of Gleason Grade Group 5 in a Contemporary Prostate Cancer Grading System and Literature Review

    Kamitani R., Matsumoto K., Kosaka T., Takeda T., Hashiguchi A., Tanaka N., Morita S., Mizuno R., Shinojima T., Asanuma H., Oya M.

    Clinical Genitourinary Cancer (Clinical Genitourinary Cancer)   2020

    ISSN  15587673

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    © 2020 Elsevier Inc. Introduction: The aim of this study was to validate contemporary grading systems, in particular, the Gleason grade group (GGG) 5. Patients and Methods: We retrospectively reviewed the clinicopathologic data of 176 patients who underwent radical prostatectomy and whose pathologic results were GGG 4 or 5. The endpoints were biochemical recurrence (BCR) and castration-resistant prostate cancer (CRPC). Results: The GGG 4 group was composed of 69 patients. The GGG 5 group consisted of 78 patients with GS 4+5 and 29 patients with GS 5+4 or higher. The 5-year BCR-free survival rates for men with GGG 4, GS 4+5, and GS 5+4 or higher were 59%, 54%, and 20%, respectively, and the 5-year CRPC-free survival rates were 98%, 100%, and 88%, respectively. Both the BCR- and CRPC-free survival rates were significantly higher in GS 4+5 than in GS 5+4 or higher (P < .001 and P = .002, respectively), but there were no significant differences between GGG 4 and GS 4+5 (P = .702 and P = .803, respectively). The multivariate analysis demonstrated that GS 5+4 or higher (hazard ratio, 3.4; P = .002) and lymphovascular invasion (hazard ratio, 3.4; P < .001) greatly affected BCR. Conclusion: Our follow-up study revealed that men with GS 4+5 and those with GGG 4 had a similar prognosis. However, there was a significant discrepancy in prognosis between GS 4+5 and GS 5+4 or higher. This suggested that GGG 4 and 5 in the contemporary prostate cancer grading system should be reviewed. Furthermore, lymphovascular invasion may be useful to subgroup these pathologically high-risk patients.

  • Maternal undernutrition aggravates renal tubular necrosis and interstitial fibrosis after unilateral ureteral obstruction in male rat offspring

    Awazu M., Abe T., Hashiguchi A., Hida M.

    PLoS ONE (PLoS ONE)  14 ( 9 )  2019.09

     View Summary

    © 2019 Awazu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Maternal undernutrition is known to reduce glomerular number but it may also affect tubulointerstitium, capillary density, and response to oxidative stress. To investigate whether the latter elements are affected, we examined the response to unilateral ureteral obstruction (UUO), an established model of renal tubulointerstitial fibrosis, in the kidney of offspring from control and nutrient restricted rats. Six-week old male offspring from rats given food ad libitum (CON) and those subjected to 50% food restriction throughout pregnancy (NR) were subjected to UUO for 7 days. Body weight was significantly lower in NR. Systolic blood pressure and blood urea nitrogen increased similarly in CON and NR after UUO. Tubular necrosis in the obstructed kidney, on the other hand, was more extensive in NR. Also, the collagen area, a marker of fibrosis, of the obstructed kidney was significantly increased compared with the contralateral kidney only in NR. Capillary density was decreased similarly in the obstructed kidney of CON and NR compared with the contralateral kidney. Urine nitrate/ nitrite, a marker of nitric oxide production, from the obstructed kidney was significantly increased in NR compared with CON. Nitrotyrosine, a marker of nitric oxide-mediated free radical injury, was increased in the obstructed kidney compared with the contralateral kidney in both CON and NR, but the extent was significantly greater in NR. In conclusion, more severe tubular necrosis and fibrosis after UUO was observed in NR, which was thought to be due to increased nitrosative stress.

  • Acute Interstitial Nephritis With Karyomegalic Epithelial Cells After Nivolumab Treatment—Two Case Reports

    Ryuzaki M., Tokuyama H., Uchiyama K., Nakaya H., Hasegawa K., Miyashita K., Konishi K., Hashiguchi A., Wakino S., Itoh H.

    Clinical Medicine Insights: Case Reports (Clinical Medicine Insights: Case Reports)  12 2019.06

     View Summary

    © The Author(s) 2019. Clinical application of immune checkpoint inhibitors (CPIs) including nivolumab is expanding in the field of oncology treatment. Nivolumab is an anti-programmed death 1 protein (PD-1) antibody designed to augment an immunologic reaction against cancer cells. On the contrary, CPIs are known to cause a unique variety of side effects termed as immune-related adverse events, which can affect any organ including kidney. However, the characteristics of renal disorders by nivolumab treatment are poorly described. We describe two cases of acute kidney injury that were treated with nivolumab. Two patients, one with renal-cell carcinoma and the other with lung cancer, exhibited progressive renal dysfunction after the initiation of nivolumab treatment. By kidney biopsy, each case was diagnosed as acute interstitial nephritis (AIN). Of note, tubular epithelial cells enlarged with hyperchromatic nuclei were focally observed, and this finding was consistent with karyomegalic tubular epithelial cells. In immunostaining, most of the enlarged tubular epithelial cells were positive for Ki-67, which suggested regeneration of tubular epithelial cells. Clinically, in one case, renal function was partially recovered with the discontinuation of nivolumab, while in another case renal function was fully recovered with additional corticosteroid treatment. We presented nivolumab-induced AIN with karyomegalic changes of tubular epithelia. We propose that immunosuppressive therapy may be necessary for the full recovery from renal impairment.

  • Effectiveness of color correction on the quantitative analysis of histopathological images acquired by different whole-slide scanners

    Aziz M., Nakamura T., Yamaguchi M., Kiyuna T., Yamashita Y., Abe T., Hashiguchi A., Sakamoto M.

    Artificial Life and Robotics (Artificial Life and Robotics)  24 ( 1 ) 28 - 37 2019.03

    ISSN  14335298

     View Summary

    © 2018, ISAROB. Advances in whole-slide scanning have led to research on digital pathology, including monitor-based diagnosis, feature quantification, and computer-aided diagnosis. The color variations due to the staining process and scanning device are a serious issue that should be solved in whole-slide imaging applications, and methods for color correction have been studied. Nevertheless, the effectiveness of color-correction methods in the quantitative analysis of histopathological images acquired by different whole-slide scanners (WSSs) has not been confirmed. In this work, several liver tissue samples were scanned by different WSSs, and a color-correction method for whole-slide images was applied to the digitized tissue specimens. A set of histological features were extracted from the histopathological images, both without and with color correction, to analyze the effectiveness of the color-correction method in feature quantification and cancer identification.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

Presentations 【 Display / hide

  • Effectiveness of color correction on the quantitative analysis of histopathological images acquired by different whole-slide scanners

    Aziz Maulana Abdul, Nakamura Tomoya, Yamaguchi Masahiro, Kiyuna Tomoharu, Yamashita Yoshiko, Abe Tokiya, Hashiguchi Akinori, Sakamoto Michiie

    Artificial Life and Robotics, 2018.01

     View Summary

    <p>Advances in whole-slide scanning have led to research on digital pathology, including monitor-based diagnosis, feature quantification, and computer-aided diagnosis. The color variations due to the staining process and scanning device are a serious issue that should be solved in whole-slide imaging applications, and methods for color correction have been studied. Nevertheless, the effectiveness of color-correction methods in the quantitative analysis of histopathological images acquired by different whole-slide scanners (WSSs) has not been confirmed. In this work, several liver tissue samples were scanned by different WSSs, and a color-correction method for whole-slide images was applied to the digitized tissue specimens. A set of histological features were extracted from the histopathological images, both without and with color correction, to analyze the effectiveness of the color-correction method in feature quantification and cancer identification.</p>

  • Extraction of glomeruli in whole slide imaging of kidney biopsy specimens

    Ishikawa Masahiro, Watanabe Sumire, Honda Natsuki, Kobayashi Naoki, Abe Tokiya, Hashiguchi Akinori, Sakamoto Michiie

    2017

     View Summary

    <p>The pathological diagnosis of a transplanted kidney is made on Banff Classification in order to gain an accurate understanding of the condition of the kidney. This type of diagnosis is extremely difficult and, thus, a variety of methods for diagnosis, including diagnosis by electron microscope, are being considered at present. Quantification of the diagnostic information derived by image processing is required for such purposes. This study proposes an automatic extraction method for normal glomeruli for the purpose of quantifying Elastica Van Gieson(EVG)-stained pathology specimens. In addition, we provide a report on the package of methods that we have created for the extraction of the glomerulus in the cortex.</p>

  • 木村病と抗好中球細胞質抗体(ANCA)関連腎炎を合併した再発性多発軟骨炎

    Narabayashi Atsushi, Awazu Midori, Natsumeda Tomo, Inokuchi Mikako, Shinjou Masayoshi, Takahashi Takao, Nishikawa Takeji, Satou Shinji, Hiragata Michio, Kameyama Kaori, Hashiguchi Akinori

    第501回日本小児科学会東京都地方会, 2003.03, Oral Presentation(general)

  • In Vivo Model for Human Tumor Angiogenesis in Leukemia/Lymphoma or Multiple Myeloma and the Tumor Regression by Anti-Angiogenic Gene Therapy

    Yamada Taketo, Kondoh Kensuke, Hashiguchi Akinori, Hozumi Nobumichi, Suda Toshio, Sakamoto Michiie, Hata Jun-ichi

    Meeting of the Aerican Society of Hematology, 2002.12, Oral Presentation(general)

  • Function of D4-GDI, a Rho GTPase Regulator, in T Cell Immunity

    Kondo Kensuke, Nakata Yuji, Kuwahara Mutsumi, Hashiguchi Akinori, Fujimoto Junichiroh, Hata Jun-ichi, Yamada Taketo

    Meeting of the Aerican Society of Hematology, 2002.12, Oral Presentation(general)

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Courses Taught 【 Display / hide

  • GENERAL PATHOLOGY

    2020

  • DISEASES OF ORGAN SYSTEMS

    2020

  • GENERAL PATHOLOGY

    2019

  • DISEASES OF ORGAN SYSTEMS

    2019

Courses Previously Taught 【 Display / hide

  • 臨床実習(病理診断部)

    Keio University, 2017, Major subject, Laboratory work/practical work/exercise

  • 病理学各論(実習)

    Keio University, 2017, Major subject, Laboratory work/practical work/exercise

  • 病理学総論(実習)

    Keio University, 2017, Major subject, Laboratory work/practical work/exercise

  • 病理学各論(講義)

    Keio University, 2017, Major subject, Lecture

  • 臨床実習(病理診断部)

    Keio University, 2016, Major subject, Laboratory work/practical work/exercise

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Memberships in Academic Societies 【 Display / hide

  • The Japanese Society of Pathology

     
  • Japanese Society of Nephrology

     
  • The Japanese Society of Digital Pathology