Yasuni Nakanuma

Shizuoka Cancer Center, Sizuoka, Shizuoka, Japan

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Publications (941)3391.51 Total impact

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    ABSTRACT: Background: We aimed to identify the pathological characteristics of occupational cholangiocarcinoma. Methods: We examined the location and distribution of the carcinomas; atypical epithelium including biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB); and chronic bile duct injuries in operative or autopsy liver specimens from 16 patients. We examined the detailed pathological findings and diagnostic imaging of 3 patients. Immunohistochemical analysis using primary antibodies against γH2AX and S100P was performed. Results: BilIN and chronic bile duct injury were observed in 16 patients, and IPNB or invasive IPNB was observed in 11 patients. BilIN, IPNB, and/or chronic bile duct injury were observed in almost all the large bile ducts. Regional dilatation of the bile ducts without tumor-induced obstruction revealed such pathological changes. Highly positive results for the γH2AX and S100P markers were noted in invasive carcinoma, BilIN, and IPNB, whereas positive results for γH2AX and negative results for S100P were noted in non-neoplastic biliary epithelium. Conclusions: The carcinogenic process of occupational cholangiocarcinoma comprised chronic bile duct injury and DNA damage in almost all the large bile ducts, along with induction of precancerous lesions and development of invasive carcinoma. Such pathological findings reflected radiological changes on diagnostic imaging. This article is protected by copyright. All rights reserved.
    Journal of Hepato-Biliary-Pancreatic Sciences 11/2015; DOI:10.1002/jhbp.305 · 2.99 Impact Factor
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    Susumu Tazuma · Yasuni Nakanuma ·
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    ABSTRACT: Background: Hepatolithiasis is a calculus disease of the liver with no known cause that is relatively uncommon, and is characterized by a refractory nature and high frequency of recurrence. Hepatolithiasis is one of the diseases listed by the Ministry of Health, Labour and Welfare of Japan under Research on Intractable Diseases, and it requires further research on the pathogenesis as well as the therapeutic strategy. It is also included in the clinical guidelines for cholelithiasis of the Japanese Society of Gastroenterology, which suggest guiding principles for the treatment of hepatolithiasis. Methods: we performed questionnaire surveys of hepatolithiasis twice in 2010 and in 2012. Verification of the evidence-based clinical practice guidelines a questionnaire survey of 22 facilities in 2010 and 25 facilities in 2012 across Japan that provided cooperation, which enabled us to assess 210 new cases over a two-year period. Conclusions: Comparison with two surveys that have been carried out previously revealed the main factor associated with hepatolithiasis was a history of biliary tract surgery, which was noted in the majority of cases. In addition, there was an increase of patients in whom balloon endoscopy was performed using transduodenal approach. This method is not included in the treatment options of the current clinical guidelines for cholelithiasis, so there may be a need to take it into consideration when the guidelines are revised.
    Lipids in Health and Disease 10/2015; 14(1):129. DOI:10.1186/s12944-015-0130-2 · 2.22 Impact Factor
  • Motoko Sasaki · Yasuni Nakanuma ·
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    ABSTRACT: This chapter reviews a new type of hepatocellular neoplasm, serum amyloid A-positive hepatocellular neoplasm (SAA-HN), which arises in patients with advanced alcoholic liver disease such as cirrhosis. SAA-HNs share histological and immunohistochemical features with inflammatory hepatocellular adenoma, for example, a strong immunoreactivity for SAA. Clinicopathological features and issues regarding SAA-HN are reviewed with emphasis regarding its potential to develop into hepatocellular carcinoma.
    Digestive Diseases 09/2015; 33(5):648-654. DOI:10.1159/000438474 · 2.18 Impact Factor
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    ABSTRACT: Deregulated autophagy followed by cellular senescence in biliary epithelial cells (BECs) may be closely related to the abnormal expression of mitochondrial antigens and following autoimmune pathogenesis in primary biliary cirrhosis (PBC). We examined an involvement of endoplasmic reticulum (ER) stress in the deregulated autophagy and cellular senescence in PBC. We examined the degree of ER stress using markers; glucose-regulated protein 78 (GRP78) and protein disulfide isomerases (PDI), autophagy and cellular senescence in cultured BECs treated with an ER stress inducer, tunicamycin (TM), glycochenodeoxycholic acid (GCDC), and palmitic acid (PA), and the effect of pretreatment with tauroursodeoxycholic acid (TUDCA). We examined the expression of PDI and GRP78 in livers taken from the patients with PBC (n = 43) and 75 control livers. The expression of ER stress markers was significantly increased in cultured BECs treated with TM, GCDC or PA in BECs (p < 0.05), and pretreatment with TUDCA significantly suppressed the induced ER stress (p < 0.05). Autophagy, deregulated autophagy, and cellular senescence were induced in BECs treated with TM, GCDC, or PA. Pretreatment with TUDCA further increased autophagy in BECs treated with PA and suppressed cellular senescence caused by treatments with TM, GCDC, or PA (p < 0.05). A granular expression of PDI and GRP78 was significantly more extensive in small bile ducts in PBC, compared with control livers (p < 0.05). The expression of GRP78 was seen in senescent BECs in PBC. ER stress may play a role in the pathogenesis of deregulated autophagy and cellular senescence in biliary epithelial lesions in PBC.
    Journal of Gastroenterology 09/2015; 50(9). DOI:10.1007/s00535-014-1033-0 · 4.52 Impact Factor
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    ABSTRACT: Intraductal papillary or tubular neoplasms of the bile duct have recently been proposed as one of the pre-invasive lesions of cholangiocarcinoma. Herein, a total of 50 cases of intraluminal polypoid neoplasms of the bile ducts experienced in Khon Kaen University Hospital in Thailand were pathologically examined. These cases presumably had a history of infection of Opisthorchis viverrini. These neoplasms were histologically composed of high-grade intraepithelial neoplasm showing a tubular and/papillary pattern without invasion (20 cases), and with minimal and considerable invasion (15 and 15 cases, respectively). They were histologically classifiable into papillary type (10 cases), tubular type (20 cases) and papillotubular type (20 cases), and were phenotypically classifiable into gastric (17 cases), intestinal (17 cases) and pancreatobiliary types (16 cases). It was found that cases of papillary type and gastric or intestinal phenotype were less invasive, while those of tubular or papillotubular type and pancreatobiliary phenotype were more invasive. In conclusion, intraductal polypoid neoplasms in Thailand were well-differentiated papillary and/or tubular neoplasms including those with no or minimal invasion, and histological and phenotypic subclassifications seem to be useful for evaluation of the aggressive pathological behaviors of these neoplasms.
    International journal of clinical and experimental pathology 09/2015; 8(7):8284-90. · 1.89 Impact Factor
  • Motoko Sasaki · Maylee Hsu · Matthew M Yeh · Yasuni Nakanuma ·
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    ABSTRACT: In biliary epithelial lesions in primary biliary cirrhosis (PBC), mitochondrial proteins associated with deregulated autophagy are abnormally expressed. We examined whether this could be used as a diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation. We examined the expression of the mitochondrial protein pyruvate dehydrogenase complex-E2 component and cytochrome c oxidase, subunit I (CCO), the autophagy-related marker microtubule-associated protein-light chain 3 (LC3), and p62/sequestosome-1 and the senescence markers p16(Ink4a) and p21(WAF1/Cip1) in small bile ducts and bile ductules in explanted livers from patients with PBC (n = 20) in comparison with liver tissue from control patients (n = 21) and post-transplant samples including recurrent PBC and cellular rejection (n = 28). Intense granular expression of mitochondrial proteins was significantly more frequent in small bile ducts in explanted livers with PBC than in control livers (p < 0.05). Post-transplant samples comprised of three groups: group A (positive for mitochondrial proteins, n = 7), group B (positive for either autophagy-related or senescence markers but negative for mitochondrial proteins, n = 7), and group C (all negative, n = 14). All but one case of group A were clinically and histologically diagnosed as recurrent PBC. In contrast, all cases of group B were diagnosed as cellular rejection. This study suggests that the expression of mitochondrial proteins in small bile ducts may be a useful diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2015; 467(4). DOI:10.1007/s00428-015-1819-3 · 2.65 Impact Factor
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    ABSTRACT: Glycoform of mucin 1 (MUC1) in cancerous cells changes markedly with cell differentiation, and thus qualitative detection and verification of the MUC1 glycosylation changes have potential diagnostic value. We have developed an ultrasensitive method to detect the changes in cholangiocarcinoma (CC), which produces MUC1, and applied it in the diagnostics development. The focused glycan analysis using 43-lectin-immobilized microarray could obtain the glycan profiles of sialylated MUC1 in 5 μL of sera. The high-throughput analysis detected disease-specific alterations of glycosylation, and the statistical analysis confirmed that use of Wisteria floribunda agglutinin (WFA) alone produced a diagnostic score sufficient for discriminating 33 CC cases from 40 hepatolithiasis patients and 48 normal controls (p < 0.0001). The CC-related glycosylation change was verified by the lectin-antibody sandwich ELISA with WFA in two cohorts: (1) 78 Opisthorchis viverrini infected patients without CC and 78 with CC, (2) 33 CC patients and 40 hepatolithiasis patients (the same cohort used for the above lectin microarray). The WFA positivity distinguished patients with CC (opisthorchiasis: p < 0.0001, odds ratio = 1.047; hepatolithiasis: p = 0.0002, odds ratio = 1.018). Sensitive detection of qualitative alterations of sialylated MUC1 glycosylation is indispensable for the development of our glycodiagnostic test for CC.
    Analytical Chemistry 06/2015; 87(14). DOI:10.1021/acs.analchem.5b01329 · 5.64 Impact Factor
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    ABSTRACT: A rare case of an intrahepatic multicystic tumor is described. A 26-year-old man visited our hospital because of abdominal discomfort. Contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography revealed a 10 × 7 cm multicystic tumor of the bile duct in the right side of the liver. The gross appearance of the tumor resembled an intraductal papillary neoplasm of the bile duct, and right hepatectomy with regional lymphadenectomy was performed. Histologically, these cystic lesions were composed of variably and irregularly dilated duct structures lined by columnar epithelium resembling bile duct lining. There were no atypical cells and no papillary growth of the epithelial cells. Interestingly, the dilated ducts contained inspissated bile, and the inter-cystic parenchyma contained variable but irregularly distributed and hamartomatous hepatic parenchyma with an abnormal lobular pattern. Though it had atypical features of a hamartoma in some aspects (age, smooth muscle), this case could finally be regarded as a variant of multicystic biliary hamartoma.
    Clinical Journal of Gastroenterology 05/2015; 8(3). DOI:10.1007/s12328-015-0574-y
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    ABSTRACT: Given that pancreatic ductal adenocarcinoma (PDAC) is among the most fatal malignancies with an extremely poor prognosis, the objectives of this study were to provide a detailed understanding of PDAC pathophysiology in view of the host immune response. We examined the PDAC tissues, sera, and peripheral blood cells of PDAC patients using immunohistochemical staining, the measurement of cytokine/chemokine concentrations, gene expression analysis, and flow cytometry. PDAC tissues were infiltrated by macrophages, especially CD33+CD163+ M2 macrophages and CD4+ T cells that concomitantly express programmed cell death-1 (PD-1). Concentrations of interleukin (IL)-6, IL-7, IL-15, monocyte chemotactic protein-1, and interferon-inducible protein-1 in the sera of PDAC patients were significantly elevated. The gene expression profile of CD14+ monocytes and CD4+ T cells was discernible between PDAC patients and healthy volunteers, and the differentially expressed genes were related to activated inflammation. Intriguingly, PD-1 was significantly up-regulated in the peripheral blood CD4+ T cells of PDAC patients. Correspondingly, the frequency of CD4+PD-1+ T cells increased in the peripheral blood cells of PDAC patients, and this increase correlated to chemotherapy resistance. In conclusion, inflammatory condition in both the PDAC tissue and peripheral blood cells in PDAC patients were prominent, highlighting monocytes/macrophages as well as CD4+ T cells with influence of the clinical prognosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Cancer Science 04/2015; 106(6). DOI:10.1111/cas.12663 · 3.52 Impact Factor
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    ABSTRACT: The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract and ampullary carcinomas in 2008. Novel treatment modalities and handling of clinical issues have been proposed after the publication. New approaches for editing clinical guidelines, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, also have been introduced for better and clearer grading of recommendations. Clinical questions (CQs) were proposed in seven topics. Recommendation, grade of recommendation and statement for each CQ were discussed and finalized by evidence-based approach. Recommendation was graded to grade 1 (strong) and 2 (weak) according to the concept of GRADE system. The 29 CQs covered seven topics: (1) prophylactic treatment, (2) diagnosis, (3) biliary drainage, (4) surgical treatment, (5) chemotherapy, (6) radiation therapy, and (7) pathology. In 27 CQs, 19 recommendations were rated strong and 11 recommendations weak. Each CQ included the statement of how the recommendation was graded. This guideline provides recommendation for important clinical aspects based on evidence. Future collaboration with cancer registry will be a key for assessment of the guidelines and establishment of new evidence. Free full-text articles and a mobile application of this guideline are available via http://www.jshbps.jp/en/guideline/biliary-tract2.html. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
    Journal of Hepato-Biliary-Pancreatic Sciences 03/2015; 22(4). DOI:10.1002/jhbp.233 · 2.99 Impact Factor
  • Yasuni Nakanuma · Yuko Kakuda ·

    Nippon rinsho. Japanese journal of clinical medicine 03/2015; 73 Suppl 3:471-6.
  • Yasuni Nakanuma · Yuko Kakuda ·

    Nippon rinsho. Japanese journal of clinical medicine 03/2015; 73 Suppl 3:455-60.
  • Yasunori Sato · Kenichi Harada · Motoko Sasaki · Yasuni Nakanuma ·
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    ABSTRACT: Alteration in intrahepatic microcirculation of IPH has been poorly understood. This study aimed to characterize altered intrahepatic microcirculation of idiopathic portal hypertension (IPH) focusing on the expression pattern of glutamine synthetase (GS). Immunohistochemical staining of GS was performed using liver sections of IPH (n = 28). Serial section analysis was performed to determine microcirculatory disturbances of IPH. Paraportal shunt vessels were observed in 20 cases of IPH, and they were divided into two types according to the GS staining pattern; hepatocytes surrounding the vessels were negative for GS (Type 1) and positive for GS (Type 2). All 20 cases had one or more Type 1 vessels within a section, and 10 cases were further associated with Type 2 vessels. The cases with Type 2 vessels showed infrequent symptoms of esophageal varices. Regarding the GS staining as an indicator of hepatic veins, some of Type 2 vessels were supposed to represent portovenous shunts. Isolated arteries in hepatic parenchyma were present in 21 cases, and they were located around terminal hepatic venules in 6 cases, corresponding to centrizonal arteries. Broad hepatocellular GS staining in hyperplastic lesions was noted in 5 cases, whereas nodular regenerative hyperplasia lacked GS expression. GS immunostaining revealed microcirculatory disturbances of IPH that were associated with abnormalities in both venous and arterial vessels. This article is protected by copyright. All rights reserved.
    Hepatology Research 02/2015; DOI:10.1111/hepr.12506 · 2.74 Impact Factor
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    ABSTRACT: The 3(rd) English edition of the Japanese classification of biliary tract cancers was released approximately 10 years after the 5(th) Japanese edition and the 2(nd) English edition. Since the first Japanese edition was published in 1981, the Japanese classification has been in extensive use, particularly among Japanese surgeons and pathologists, because the cancer status and clinical outcomes in surgically resected cases have been the main objects of interest. However, recent advances in the diagnosis, management and research of the disease prompted the revision of the classification that can be used by not only surgeons and pathologists but also by all clinicians and researchers, for the evaluation of current disease status, the determination of current appropriate treatment, and the future development of medical practice for biliary tract cancers. Furthermore, during the past 10 years, globalization has advanced rapidly, and therefore, internationalization of the classification was an important issue to revise the Japanese original staging system, which would facilitate to compare the disease information among institutions worldwide. In order to achieve these objectives, the new Japanese classification of the biliary tract cancers principally adopted the 7(th) edition of staging system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). However, because there are some points pending in these systems, several distinctive points were also included for the purpose of collection of information for the future optimization of the staging system. Free mobile application of the new Japanese classification of the biliary tract cancers is available via http://www.jshbps.jp/en/classification/cbt15.html. © Japanese Society of Hepato-Biliary-Pancreatic Surgery.
    Journal of Hepato-Biliary-Pancreatic Sciences 02/2015; 22(3). DOI:10.1002/jhbp.211
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    ABSTRACT: Purpose: To identify the imaging features of hepatocellular carcinoma (HCC) associated with β-catenin mutation and their relationship to pathologic findings. Materials and methods: Institutional ethics committee approval and informed consent were obtained. One hundred thirty-eight surgically resected HCCs were analyzed in this study. Immunohistochemical expression of β-catenin and its transcriptional product, glutamine synthetase (GS), were graded and classified into three groups: the β-catenin positive and GS positive group (HCC with β-catenin mutation), the β-catenin negative and GS positive group (intermediate HCC), and the β-catenin negative and GS negative group (HCC without β-catenin mutation). Clinical, pathologic, and imaging findings from dynamic computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance (MR) imaging (T1-weighted, T2-weighted, diffusion-weighted, and hepatobiliary phase imaging) were evaluated. Correlations among immunohistochemical expression of β-catenin, GS, and organic anion transporting polypeptide 1B3 (uptake transporter of gadoxetic acid) were evaluated. The χ(2), Kruskal-Wallis, and Spearman correlation tests were used. Results: HCCs with β-catenin mutation (n = 27) showed a lower median contrast-to-noise ratio at diffusion-weighted imaging than did intermediate HCCs (n = 23) and HCCs without β-catenin mutation (n = 84) (13.2, 24.4, and 27.0, respectively; P = .02), higher apparent diffusion coefficient (1.33, 1.13, and 1.12, respectively; P < .0001), higher contrast-to-noise ratio (0.58, -28.7, and -45.0, respectively; P < .0001) and higher enhancement ratio during the hepatobiliary phase (0.90, 0.50, and 0.42, respectively; P < .0001). At pathologic examination, HCCs with β-catenin mutation showed pseudoglandular proliferation and bile production with a higher grade of differentiation (P = .04, .001, and .005, respectively). There were significant positive correlations among expression of β-catenin, GS, and organic anion transporting polypeptide 1B3 (P < .0001). Conclusion: HCCs with β-catenin mutation showed a higher grade of differentiation with frequent pseudoglandular patterns and bile production, and characteristic imaging findings included a high enhancement ratio at gadoxetic acid-enhanced MR imaging and a high apparent diffusion coefficient at diffusion-weighted imaging. Online supplemental material is available for this article.
    Radiology 02/2015; 275(3):141315. DOI:10.1148/radiol.14141315 · 6.87 Impact Factor
  • Yasuni Nakanuma · Yuko Kakuda ·
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    ABSTRACT: Herein, we propose a new pathologic classification of cholangiocarcinoma (CCA) based on recent progress in studies of preinvasive CCA lesions and the relationship of CCA to hepatic progenitor cells, as well as a new concept with respect to the pathologic similarities between biliary and pancreatic neoplasms. Depending on anatomical location, CCA is classifiable as intrahepatic (iCCA), perihilar (pCCA), and distal CCA (dCCA). iCCA is classifiable as the conventional type and the bile ductular type, whereas pCCA and dCCA mainly present as conventional adenocarcinoma. In addition, these three CCAs may present as the intraductal neoplasm type or rare variants. Bile ductular CCA resembles proliferating bile ductules and expressing hepatic progenitor cell phenotypes. Four types of preinvasive lesions are proposed: flat, papillary, tubular lesion, and cystic lesion. These lesions are eventually followed by invasive CCA. Interestingly, these preinvasive lesions have pancreatic counterparts. This CCA classification may introduce a new field of CCA research. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Baillière&#x027 s Best Practice and Research in Clinical Gastroenterology 02/2015; 29(2). DOI:10.1016/j.bpg.2015.02.006 · 3.48 Impact Factor
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    ABSTRACT: The liver biopsy remains a valuable tool in the diagnosis of drug-induced liver injury (DILI). The Digestive Disease Week Japan 2004 (DDW-J) scale proposed as an objective tool for the diagnosis of DILI has been widely used in Japan. So far, the histological features have not been compared with DDW-J scale in detail. Herein, we examined the correlation between liver biopsy findings and clinical features, particularly DDW-J scales. A total of 80 patients with liver injuries of unknown cause were enrolled. Based on the histological findings, these cases were categorized into 3 groups: A (DILI was strongly suspected), B (DILI was suspected), and C (DILI should be considered in the differential diagnosis). Histological groups and DDW-J scale were moderately correlated ( κ = 0.60 ). The mean total DDW-J scale scores were as follows: 4.89 for A, 3.26 for B, and 0.75 for C ( p < 0.05 ). While hepatocellular type was coincided in a majority of cases by histological and DDW-J scale evaluation, cholestatic type was not well coincided. In conclusion, biopsy findings and DDW-J scale were well correlated, and the hepatocellular type of liver injuries was well coincided by both evaluations, though there were several discrepant cases, particularly in cholestatic type.
    Mediators of Inflammation 01/2015; 2015(8):1-9. DOI:10.1155/2015/913793 · 3.24 Impact Factor
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    ABSTRACT: A 54-year-old woman was referred to our hospital for further examination of a hepatic mass detected on abdominal US. The blood test revealed a positive but mild inflammatory response. Hepatic virus markers were negative. Abdominal CT showed a fatty mass, 10cm in diameter, in segments 7 and 8, containing hypervascular nodules showing early enhancement in the arterial phase and washout in the equilibrium phase. She presented with a high fever of over 39oC during a work-up period, and the blood test revealed a marked inflammatory response. Abdominal CT and MRI after developing fever indicated intratumoral hemorrhage. There was no other evidence of infection. We suspected hepatocellular carcinoma with intratumoral hemorrhage based on these imaging findings. Although we considered other benign tumors in the differential diagnosis, she underwent right hepatectomy because the tumor was symptomatic. Histologically, the tumor was composed of smooth muscle cells, vessels, and adipose cells with marked infiltration of inflammatory cells and bleeding. On immunohistochemical staining, the tumor was positive for human melanoma black-45. The tumor was diagnosed as inflammatory angiomyolipoma of the liver with intratumoral hemorrhage.
    Nippon Shokaki Geka Gakkai zasshi 01/2015; 48(8):677-683. DOI:10.5833/jjgs.2014.0221
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    ABSTRACT: We thank Dr. Tapan and Sertoglu for their interest in our study and their comments. In the letter to the Editor, they recommend to measure fatty acid composition after excluding patients with type 2 diabetes mellitus (T2DM) because the activity of the desaturase enzymes regulating especially polyunsaturated fatty acids can be affected by T2DM and correlates with the level of fasting plasma glucose and insulin resistance [1]. In our study, HbA1c levels are 7.1±0.2% and 7.1±0.3% for simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) groups, respectively, and the patients with T2DM are included in both SS and NASH groups. The number of patients with T2DM was 42/63 (66.7%) and 29/40 (72.5%) for SS and NASH groups, respectively, and there was no statistically significant difference in the rate of T2DM between SS and NASH groups. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 12/2014; DOI:10.1111/liv.12755 · 4.85 Impact Factor
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    ABSTRACT: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) occurring after liver transplantation is a relatively rare complication but it often takes a life-threatening course. However, the detailed etiology and mechanism of VOD/SOS after liver transplantation (LT) remains unclear. We report two cases with rapidly progressive VOD/SOS after ABO-identical LT resistant to various therapies. In case 1, in which the patient underwent deceased-donor LT, the first episode of acute allograft rejection was triggered VOD/SOS, and the presence of donor non-specific anti-HLA antibodies was confirmed. The recipient died with graft failure on day 46 after transplantation. Case 2, in which the patient underwent living-donor LT from the mother, had neither rejection nor mechanical venous obstruction, but condition of the patient rapidly worsened and he died on day 13 after transplantation. This recipient's direct cross-match test for the donor's B lymphocyte was strongly positive, but that for T lymphocyte was negative. In both cases, neither stenosis of hepatic vein outflow tract nor C4d deposition in post-transplantation liver biopsy specimens and autopsy specimen was found. On the other hand, in both cases, the patient was transfusion unresponsive thrombocytopenia and hyperbilirubinemia persisted postoperatively, and glycoprotein Ⅰ bα was strongly stained in the neighboring centrilobular area (zone 3), especially in the space of Disse, and platelet phagocytosis was observed in Kupffer cells and hepatocytes around zone 3 such as clinical xenotransplantation of the liver in post-transplantation liver biopsy specimens. From the viewpoint of graft injury, VOD/SOS was considered that sustained sinusoidal endothelial cells injury resulted in bleeding in the space of Disse and led to around centrilobular hemorrhagic necrosis, and the fundamental cause was damage around centrilobular area including sinusoid by acute cellular rejection, antibody-mediated rejection or ischemic reperfusion injury. The extrasinusoidal platelet activation, aggregation, and phagocytosis of platelets were some of the main reasons for VOD/SOS and transfusion-resistant thrombocytopenia. Copyright © 2014 Elsevier Inc. All rights reserved.
    Transplantation Proceedings 12/2014; 46(10):3523-35. DOI:10.1016/j.transproceed.2014.09.110 · 0.98 Impact Factor

Publication Stats

24k Citations
3,391.51 Total Impact Points


  • 2014-2015
    • Shizuoka Cancer Center
      Sizuoka, Shizuoka, Japan
  • 1979-2015
    • Kanazawa University
      • • School of Medicine
      • • Department of Internal Medicine
      Kanazawa, Ishikawa, Japan
  • 1987-2014
    • Kanazawa Medical University
      • • Department of Radiology
      • • Department of Pathology
      Kanazawa, Ishikawa, Japan
  • 2008
    • Japanese Red Cross
      Edo, Tōkyō, Japan
    • Ishikawa Prefectural Central Hospital
      Ishiza, Okinawa, Japan
  • 2003
    • NHO Nagasaki Medical Center
      Nagasaki, Nagasaki, Japan
  • 1998
    • Virginia Commonwealth University
      • Department of Pathology
      Ричмонд, Virginia, United States
  • 1995-1997
    • University of California, Davis
      • Division of Rheumatology/Allergy/Clinical Immunology
      Davis, California, United States
  • 1996
    • University of California, San Francisco
      San Francisco, California, United States
  • 1994
    • Fukui Prefectural University
      Hukui, Fukui, Japan
  • 1986
    • Rancho Los Amigos Rehabilitation Center
      Downey, California, United States