Details of a Researcher - Hashiguchi, Akinori

Papers - Hashiguchi, Akinori

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腎生検糸球体病変定量化の試み

橋口明典, 石川雅浩, 城謙輔, 清水章, 久野敏, 片渕律子, 川村哲也

日本病理学会会誌 ((一社)日本病理学会) 109 ( 1 ) 435 - 435 2020.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 0300-9181

T細胞性悪性リンパ腫の腎浸潤により尿蛋白をきたした一例

押田卓磨, 徳山博文, 橋口明典, 大島洋一, 内山清貴, 脇野修, 伊藤裕

日本内科学会雑誌 ((一社)日本内科学会) 109 ( Suppl. ) 206 - 206 2020.02

Joint Work, ISSN 0021-5384

腎病理で診断に至ったFabry病を背景に多発性骨髄腫を発症したと疑われる一例

安達京華, 徳山博文, 橋口明典, 大島洋一, 伊藤智章, 脇野修, 伊藤裕

日本内科学会雑誌 ((一社)日本内科学会) 109 ( Suppl. ) 206 - 206 2020.02

Joint Work, ISSN 0021-5384

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) 19 ( 1 ) 69 - 75.e5 2020

Research paper (scientific journal), Joint Work, Accepted, ISSN 15587673

© 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.

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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 ) e0221686 2019.09

Research paper (scientific journal), Joint Work, Accepted

© 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.

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Fabry病を背景にMyeloma Cast Nephropathyを生じたと疑われる一例

安達京華, 徳山博文, 橋口明典, 大島洋一, 伊藤智章, 脇野修, 伊藤裕

日本腎臓学会誌 ((一社)日本腎臓学会) 61 ( 6 ) 773 - 773 2019.08

Joint Work, ISSN 0385-2385

イムノタクトイド腎症との鑑別が困難であったクリオグロブリン血症性糸球体腎炎の1例

相馬友美, 小杉将太郎, 伊藤智章, 神田武志, 橋口明典, 徳山博文, 脇野修, 伊藤裕

日本腎臓学会誌 ((一社)日本腎臓学会) 61 ( 6 ) 724 - 724 2019.08

Joint Work, ISSN 0385-2385

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 1179547619853647 - 1179547619853647 2019.06

Research paper (scientific journal), Joint Work, Accepted

© 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, re

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完全寛解後3ヵ月の経過で血液透析導入となった微小変化型ネフローゼ症候群の1例

山口慎太郎, 徳山博文, 橋口明典, 小西孝之助, 林晃一, 脇野修, 伊藤裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会) 19回 251 - 251 2019.06

Joint Work

IgA腎症の生検時の臨床データと病理所見の関連性

鎌野千佐子, 清水章, 城謙輔, 橋口明典, 久野敏, 片渕律子, 川村哲也

日本腎臓学会誌 ((一社)日本腎臓学会) 61 ( 3 ) 395 - 395 2019.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 0385-2385

IgA腎症のOxford分類と日本分類(組織学的重症度分類)の腎機能予後予測に関する比較

城謙輔, 中里毅, 橋口明典, 清水章, 久野敏, 片渕律子, 川村哲也

日本腎臓学会誌 ((一社)日本腎臓学会) 61 ( 3 ) 394 - 394 2019.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 0385-2385

IgA腎症のOxford分類と日本分類(組織学的重症度分類)の腎機能予後予測に関する比較

城謙輔, 橋口明典, 久野敏, 清水章

日本病理学会会誌 ((一社)日本病理学会) 108 ( 1 ) 297 - 297 2019.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 0300-9181

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

Research paper (scientific journal), Joint Work, Accepted, ISSN 14335298

© 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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経腋窩的豊胸術後の早期乳癌に対してセンチネルリンパ節生検を施行した1例

和田真弘, 橋口明典

日本外科系連合学会誌 (日本外科系連合学会) 44 ( 1 ) 13 - 20 2019.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 0385-7883

症例は48歳,女性.右乳房腫瘤を主訴に当院を受診した.既往歴として,25歳時に両側経腋窩的豊胸術(大胸筋下に生理食塩水バッグを挿入)を施行した.触診上,右乳頭直下に2cm大の腫瘤を触知した.画像検査では,乳癌が示唆された.確定診断のために針生検を提示するも,患者は拒否した.そこで,われわれは一期的な診断・手術治療を提示した.すなわち,全身麻酔下で切開生検・術中迅速病理組織検査を施行し,乳癌の場合には乳房切除+センチネルリンパ節生検+生理食塩水バッグ抜去+Tissue Expander挿入である.その方針に同意が得られた.結果は乳癌であった.センチネルリンパ節生検では転移陰性のため,腋窩リンパ節郭清は省略した.現在無再発生存中である.今後本邦では豊胸術施後の乳癌症例が増加してくることが予想される.その際のセンチネルリンパ節生検について若干の文献的考察を加えて報告する.(著者抄録)

A grading system that predicts the risk of dialysis induction in IgA nephropathy patients based on the combination of the clinical and histological severity

Okonogi H, Kawamura T, Joh K, Koike K, Miyazaki Y, Ogura M, Tsuboi N, Hirano K, Matsushima M, Yokoo T, Horikoshi S, Suzuki Y, Yasuda T, Shirai S, Shibata T, Hattori M, Akioka Y, Katafuchi R, Hashiguchi A, Hisano S, Shimizu A, Kimura K, Maruyama S, Matsuo S, Tomino Y

Clinical and Experimental Nephrology (Clinical and Experimental Nephrology) 23 ( 1 ) 16 - 25 2019.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 13421751

© 2018, The Author(s). Histological classification is essential in the clinical management of immunoglobulin A nephropathy (IgAN). However, there are limitations in predicting the prognosis of IgAN based on histological information alone, which suggests the need for better prognostic models. Therefore, we defined a prognostic model by combining the grade of clinical severity with the histological grading system by the following processes. We included 270 patients and explored the clinical variables associated with progression to end-stage renal disease (ESRD). Then, we created a predictive clinical grading system and defined the risk grades for dialysis induction by a combination of the clinical grade (CG) and the histological grade (HG). A logistic regression analysis revealed that the 24-h urinary protein excretion (UPE) and the estimated glomerular filtration rate (eGFR) were significant independent variables. We selected UPE of 0.5 g/day and eGFR of 60 ml/min/1.73 m 2 as the threshold values for the classification of CG. The risk of progression to ESRD of patients with CG II and III was significantly higher than that of patients with CG I. The patients were then re-classified into nine compartments based on the combination of CG and HG. Furthermore, the nine compartments were grouped into four risk groups. The risk of ESRD in the moderate, high, and super-high-risk groups was significantly higher than that in the low-risk group. Herein, we are giving a detailed description of our grading system for IgA nephropathy that predicted the risk of dialysis based on the combination of CG and HG.

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Non-invasive liver fibrosis assessment correlates with collagen and elastic fiber quantity in patients with hepatitis C virus infection

Yasui Y, Abe T, Kurosaki M, Matsunaga K, Higuchi M, Tamaki N, Watakabe K, Okada M, Wang W, Shimizu T, Takaura K, Masugi Y, Nakanishi H, Tsuchiya K, Takahashi Y, Itakura J, Sakurai U, Hashiguchi A, Sakamoto M, Izumi N

Hepatology Research (Hepatology Research) 49 ( 1 ) 33 - 41 2019.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 13866346

© 2018 The Japan Society of Hepatology Aim: Elastic fiber deposition is a cause of irreversibility of liver fibrosis. However, to date, its relevance to clinical features has not yet been clarified. This study aimed to clarify the correlation between non-invasive markers of fibrosis and fiber quantity, including elastic fiber, obtained from computational analysis. Methods: This retrospective study included 270 patients evaluated by non-invasive liver fibrosis assessment prior to liver biopsy. Of these patients, 95 underwent magnetic resonance elastography (MRE) and 244 were assessed with Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA + -M2BP). Using whole-slide imaging of Elastica van Gieson-stained liver biopsy sections, the quantity of collagen, elastin, and total fiber (elastin + collagen) was determined. Results: The total fiber quantity showed significant linear correlation with fibrosis stage F0–F4. Collagen fiber quantity increased from stage F0 to F4, whereas elastic fiber quantity increased significantly only from stage F2 to F3. Spearman's rank correlation test revealed that non-invasive liver fibrosis assessment significantly correlates with each fiber quantity, including correlation between total fiber quantity and the Fibrosis-4 (FIB-4) index (r = 0.361, P < 0.001), WFA + -M2BP values (r = 0.404, P < 0.001), and liver stiffness value by MRE (r = 0.615, P < 0.001). Receiver operating characteristic (ROC) curve analyses revealed that the area under ROC for predicting higher elastic fiber (>3.6%) is 0.731 by FIB-4 index, 0.716 by WFA + -M2BP, and 0.822 by liver stiffness by MRE. Conclusion: Liver fibrosis correlates with fiber quantity through non-invasive assessment regardless of fiber type, including elastic fiber. Moreover, MRE is useful for predicting high amounts of elastic fiber.

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Prediction of extraprostatic extension by MRI tumor contact length: difference between anterior and posterior prostate cancer

Matsumoto K, Akita H, Narita K, Hashiguchi A, Takamatsu K, Takeda T, Kosaka T, Mizuno R, Kikuchi E, Oya M, Jinzaki M

Prostate Cancer and Prostatic Diseases (Prostate Cancer and Prostatic Diseases) 22 ( 4 ) 539 - 545 2019

Research paper (scientific journal), Joint Work, Accepted, ISSN 13657852

© 2019, Springer Nature America, Inc. Background: Tumor contact length (TCL) is defined as the extent of contact between prostate cancer and the prostatic capsule, and its predictive value for microscopic extraprostatic extension (EPE) has been reported. However, the impact of the zonal origin (anterior or posterior tumor) of the tumor on the diagnosis of EPE is controversial. Methods: We retrospectively analyzed the records of 233 consecutive patients who underwent preoperative MRI and radical prostatectomy. We designated their tumors as anterior or posterior, and evaluated the correlation between the TCL measured by MRI and microscopic EPE in the radical prostatectomy specimen. Then, we created the predicted probability curves for EPE versus TCL for anterior and posterior prostate cancer. Results: There were 109 patients (47%) with an anterior tumor and 124 patients (53%) with a posterior tumor. Postoperative pathological analysis confirmed pT3 in 18 patients (17%) with an anterior tumor and in 53 patients (43%) with a posterior tumor. Multivariate analysis demonstrated that the zonal origin of the tumor was an independent predictive factor for EPE. We developed separate probability curves of EPE versus TCL for anterior and posterior prostate cancer, which revealed that anterior tumors were less likely to invade the extraprostatic tissues. Among patients whose TCL was 10–20 mm, 9/32 patients (28%) with an anterior tumor had EPE compared with 24/45 patients (53%) with a posterior tumor (p = 0.036). The decision curve of this EPE predictive model had high clinical efficacy. Conclusions: Our results indicate that anterior tumors have more favorable pathological characteristics than posterior tumors with the same TCL measured by MRI. We constructed two separate predicted probability curves for EPE after discriminating anterior and posterior tumors, which will be useful for decision making in clinical practice.

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真性多血症による二次性巣状糸球体硬化症にてネフローゼ症候群をきたした一例

藤井健太郎, 宮下和季, 徳山博文, 栗原勲, 村丘寛和, 橋口明典, 小西孝之助, 脇野修, 伊藤裕

日本内分泌学会雑誌 ((一社)日本内分泌学会) 94 ( 4 ) 1581 - 1581 2018.12

Joint Work, ISSN 0029-0661

高度の尿細管萎縮・間質線維化とともに,尿細管基底膜(TBM)にPolyclonalなimmunoglobulin Gの沈着を認めた一例

日鼻瑛, 坂巻裕介, 小西孝之助, 林晃一, 萩原正幸, 萩生田純, 香野日高, 中川健, 橋口明典

日本腎臓学会誌 ((一社)日本腎臓学会) 60 ( 6 ) 933 - 933 2018.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 0385-2385

Mesenchymal-epithelial transition of pancreatic cancer cells at perineural invasion sites is induced by Schwann cells

Fujii-Nishimura, Y., Yamazaki, K., Masugi, Y., Douguchi, J., Kurebayashi, Y., Kubota, N., Ojima, H., Kitago, M., Shinoda, M., Hashiguchi, A. and Sakamoto, M.

Pathol Int (Pathology International) 68 ( 4 ) 214 - 223 2018.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 1440-1827

Epithelial-mesenchymal transition (EMT) promotes invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the importance of its reverse process, mesenchymal-epithelial transition (MET), for PDAC remains unclear. We aimed to characterize the histological finding "focal differentiation" in PDAC at perineural invasion sites in the context of MET and to investigate the role of Schwann cells in inducing tumor MET. Tumor differentiation and immunohistochemical expressions of E-cadherin, SMAD3, and vimentin at perineural invasion sites were examined in 168 PDAC tissues. Four PDAC cell lines were co-cultured with Schwann cells to investigate cell morphology, motility, or EMT-related markers using immunocytochemistry and quantitative PCR. Of 168 tumors, 124 (74%) showed focal differentiation with enhanced E-cadherin membrane expression (P < 0.001) and decreased nuclear accumulation of SMAD3 (P < 0.001). Among 115 PDACs harboring grade 1/2 tumor, tumors with focal differentiation showed worse survival compared to those without focal differentiation (P = 0.019). PDAC cells co-cultured with Schwann cells demonstrated a sheet-like appearance, increased E-cadherin expression, decreased expressions of SMAD3 and vimentin, and reduced cell motility. In conclusion, MET-like change is induced by Schwann cells, suggesting that Schwann cells contribute to PDAC colonization in pancreatic nerves through activating the MET machinery inside tumor cells in the pancreatic tumor microenvironment.

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