研究者詳細 - 橋口　明典

論文 - 橋口　明典

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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年06月

共著

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年05月

研究論文（学術雑誌）, 共著, 査読有り, 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年05月

研究論文（学術雑誌）, 共著, 査読有り, 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年04月

研究論文（学術雑誌）, 共著, 査読有り, 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年03月

研究論文（学術雑誌）, 共著, 査読有り, 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年02月

研究論文（学術雑誌）, 共著, 査読有り, 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年01月

研究論文（学術雑誌）, 共著, 査読有り, 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年01月

研究論文（学術雑誌）, 共著, 査読有り, 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年

研究論文（学術雑誌）, 共著, 査読有り, 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年12月

共著, 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年08月

研究論文（学術雑誌）, 共著, 査読有り, 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., Sakamoto M.

Pathology International （Pathology International） 68 （ 4 ） 214 - 223 2018年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1440-1827

© 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd 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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IgA腎症組織学的重症度分類A/C亜型の有用性の検証厚労省分科会前向き研究847症例の解析

城謙輔, 橋口明典, 清水章, 久野敏, 片渕律子, 中里毅, 川村哲也

日本腎臓学会誌（(一社)日本腎臓学会） 60 （ 3 ） 364 - 364 2018年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0385-2385

C3腎症の視点から膜性増殖性糸球体腎炎(MPGN)の再検討 MPGN I型とIII型-2nd formは同一疾患か?

佐藤直実, 城謙輔, 中村保宏, 谷内真司, 橋口明典, 高木孝士, 笹野公伸

日本病理学会会誌（(一社)日本病理学会） 107 （ 1 ） 448 - 448 2018年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0300-9181

IgA腎症における病理所見と治療反応性の検討 IgA腎症の腎病理所見と予後の関連に関する前向き多施設共同研究

片渕律子, 川村哲也, 橋口明典, 久野敏, 清水章, 城謙輔

日本腎臓学会誌（(一社)日本腎臓学会） 60 （ 3 ） 364 - 364 2018年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0385-2385

【病理診断の新潮流】発症機序を考慮した糸球体疾患の分類

橋口, 明典

腎臓内科・泌尿器科（(有)科学評論社） 7 （ 3 ） 201 - 205 2018年03月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2188-9147

Quantitative assessment of liver fibrosis reveals a nonlinear association with fibrosis stage in nonalcoholic fatty liver disease.

Yohei Masugi, Tokiya Abe, Hanako Tsujikawa, Kathryn Effendi, Akinori Hashiguchi, Masanori Abe, Yasuharu Imai, Keisuke Hino, Shuhei Hige, Miwa Kawanaka, Gotaro Yamada, Masayoshi Kage, Masaaki Korenaga, Yoichi Hiasa, Masashi Mizokami, Michiie Sakamoto

Hepatology communications （Hepatology Communications） 2 （ 1 ） 58 - 68 2018年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2471-254X

Accurate staging of liver fibrosis is crucial to guide therapeutic decisions for patients with nonalcoholic fatty liver disease (NAFLD). Digital image analysis has emerged as a promising tool for quantitative assessment of fibrosis in chronic liver diseases. We sought to determine the relationship of histologic fibrosis stage with fiber amounts quantified in liver biopsy specimens for the better understanding of NAFLD progression. We measured area ratios of collagen and elastin fibers in Elastica van Gieson-stained biopsy tissues from 289 patients with NAFLD from four hospitals using an automated computational method and examined their correlations with Brunt's fibrosis stage. As a secondary analysis, we performed multivariable logistic regression analysis to assess the associations of the combined area ratios of collagen and elastin with noninvasive fibrosis markers. The combined fiber area ratios correlated strongly with Brunt's stage (Spearman correlation coefficient, 0.78; P < 0.0001), but this relationship was nonlinear (P = 0.007) with striking differences between stage 4 (median area ratios, 12.3%) and stages 0-3 (2.1%, 2.8%, 4.3%, and 4.8%, respectively). Elastin accumulation was common in areas of thick bridging fibrosis and thickened venous walls but not in areas of perisinusoidal fibrosis. The highest tertile of the combined fiber area ratios was associated with the fibrosis-4 index and serum type IV collagen 7s domain (7s collagen) levels, whereas the upper two tertiles of the fiber amounts significantly associated with body mass index, aspartate aminotransferase, and 7s collagen in the multivariable analysis. Conclusion: Quantitative fibrosis assessment reveals a nonlinear relationship between fibrosis stage and fiber amount, with a marked difference between stage 4 and stage 3 and much smaller differences among stages 0-3, suggesting a heterogeneity in disease severity within NAFLD-related cirrhosis. (Hepatology Communications 2018;2:58-68).

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生体腎移植後に持続血糖測定器による血糖変動の評価が有用であった2型糖尿病の3例

坂巻, 裕介, 香野, 日高, 橋口, 明典, 萩生田, 純, 萩原, 正幸, 高橋, 遼平, 與那嶺, 智子, 森田, 伸也, 篠田, 和伸, 林, 晃一 and 中川, 健

腎移植・血管外科（腎移植・血管外科研究会） 28 （ 1 ） 45 - 51 2017年10月

共著, ISSN 0915-9118

今回われわれは、生体腎移植後1年以内に、持続血糖測定(Continuous glucose monitoring;CGM)を行った2型糖尿病の3例を経験したので報告する。1例目は60歳代の男性、混合型インスリンで治療中に、随時血糖の上昇を認めCGMを施行、昼食後の血糖上昇と血糖変動幅の増大が認められ、超速効型インスリンを追加した。2例目は50歳代の女性、強化インスリン療法中に、食後の低血糖症状を認めCGMを施行、超速効型インスリンの投与時間を食前から食後へと変更する方針となった。3例目は40歳代の男性、BOT(Basal Supported Oral Therapy)治療中に、HbA1cの上昇を認めCGMを施行、食後の血糖上昇に伴う血糖変動幅の増大に対して、超速効型インスリンを開始する方針となった。このように、腎移植後の血糖変動パターンをCGMで評価することで腎移植後糖尿病のより良い治療が行える可能性が示唆された。(著者抄録)

Polycythemia, capillary rarefaction, and focal glomerulosclerosis in two adolescents born extremely low birth weight and premature

Asada, N., Tsukahara, T., Furuhata, M., Matsuoka, D., Noda, S., Naganuma, K., Hashiguchi, A. and Awazu, M.

Pediatr Nephrol （Springer Verlag） 32 （ 7 ） 1275 - 1278 2017年07月

共著, ISSN 1432-198X

BACKGROUND: Low birthweight infants have a reduced number of nephrons and are at high risk of chronic kidney disease. Preterm birth and/or intrauterine growth restriction (IUGR) may also affect peritubular capillary development, as has been shown in other organs. CASE-DIAGNOSIS/TREATMENT: We report two patients with a history of preterm birth and extremely low birthweight who showed polycythemia and renal capillary rarefaction. Patient 1 and 2, born at 25 weeks of gestation with a birthweight of 728 and 466 g, showed mild proteinuria at age 8 and 6 years, respectively. In addition to increasing proteinuria, hemoglobin levels became elevated towards adolescence and their serum erythropoietin (EPO) was high despite polycythemia. Light microscopic examination of renal biopsy specimens showed glomerular hypertrophy, focal segmental glomerulosclerosis, and only mild tubulointerstitial fibrosis. A decrease in the immunohistochemical staining of CD31 and CD34 endothelial cells in renal biopsy specimens was consistent with peritubular capillary rarefaction. CONCLUSIONS: Since kidney function was almost normal and fibrosis was not severe, we consider that the capillary rarefaction and polycythemia associated with elevated EPO levels were largely attributable to preterm birth and/or IUGR.

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【腎生検・病理診断-臨床と病理の架け橋】 (第2章)臨床医が知っておくべき腎生検標本の作製と観察の実際　光顕の標本の作製と観察　光顕所見を観察するうえでの基本と注意点

橋口, 明典

腎と透析 82 （増刊） 77 - 84 2017年05月

共著, ISSN 0385-2156

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