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Featured researches published by Wataru Koda.


Radiology | 2010

Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR Imaging--correlation with molecular transporters and histopathologic features.

Azusa Kitao; Yoh Zen; Osamu Matsui; Toshifumi Gabata; Satoshi Kobayashi; Wataru Koda; Kazuto Kozaka; Norihide Yoneda; Tatsuya Yamashita; Shuichi Kaneko; Yasuni Nakanuma

PURPOSE To analyze the correlation between signal intensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance (MR) imaging and the expression of hepatocyte transporters with histopathologic features in hepatocellular carcinoma (HCC). MATERIALS AND METHODS Institutional ethics committee approval and informed consent were obtained. Forty surgically resected HCCs were classified as hypointense (n = 32) or iso- or hyperintense (n = 8) on the basis of findings in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging. The following were compared between hypointense and iso- or hyperintense HCCs: the time-signal intensity curves at gadoxetic acid-enhanced MR imaging, the expression levels of seven transporters (four organic anion-transporting polypeptides [OATPs] and three multidrug-resistant proteins [MRPs]) at polymerase chain reaction (PCR) (for 22 nodules), results of immunostaining of OATP8, and histologic features. Statistical analysis (unpaired t test, Mann-Whitney test, chi(2) test, and Fisher exact test) was performed for each result. RESULTS On the time-signal intensity curves, hypointense HCCs showed a decreasing pattern, whereas iso- or hyperintense HCCs showed an increasing pattern after the dynamic phase. PCR revealed that expression of OATP8 (an uptake transporter) in hypointense HCCs was lower and that in iso- or hyperintense HCCs was higher than in background liver (P < .001). The expression level of MRP3 (a sinusoidal export transporter) showed a similar trend to that of OATP8 (P < .001). Immunostaining revealed that OATP8 expression was weak in hypointense HCCs, whereas it was sustained in iso- or hyperintense HCCs (P < .001). At histologic examination, a pseudoglandular proliferation pattern with bile plugs was more commonly observed in iso- or hyperintense HCCs than in hypointense HCCs (P = .01 for proliferation patterns and P = .006 for bile plugs). CONCLUSION The enhancement ratio of HCCs in the hepatobiliary phase of gadoxetic acid-enhanced MR imaging positively correlated with expression levels of OATP8 and MRP3, indicating that gadoxetic acid is taken up by OATP8 and excreted by MRP3.


European Radiology | 2011

The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging

Azusa Kitao; Osamu Matsui; Norihide Yoneda; Kazuto Kozaka; Rieko Shinmura; Wataru Koda; Satoshi Kobayashi; Toshifumi Gabata; Yoh Zen; Tatsuya Yamashita; Shuichi Kaneko; Yasuni Nakanuma

ObjectivesTo clarify the changes in organic anion-transporting polypeptide 8 (OATP8) expression and enhancement ratio on gadoxetic acid-enhanced MR imaging in hepatocellular nodules during multistep hepatocarcinogenesis.MethodsIn imaging analysis, we focused on 71 surgically resected hepatocellular carcinomas (well, moderately and poorly differentiated HCCs) and 1 dysplastic nodule (DN). We examined the enhancement ratio in the hepatobiliary phase of gadoxetic acid enhanced MR imaging [(1/postcontrast T1 value−1/precontrast T1 value)/(1/precontrast T1 value)], then analysed the correlation among the enhancement ratio, tumour differentiation grade and intensity of immunohistochemical OATP8 expression. In pathological analysis, we focused on surgically resected 190 hepatocellular nodules: low-grade DNs, high-grade DNs, early HCCs, well-differentiated, moderately differentiated and poorly differentiated HCCs, including cases without gadoxetic acid-enhanced MR imaging. We evaluated the correlation between the immunohistochemical OATP8 expression and the tumour differentiation grade.ResultsThe enhancement ratio of HCCs decreased in accordance with the decline in tumour differentiation (P < 0.0001, R = 0.28) and with the decline of OATP8 expression (P < 0.0001, R = 0.81). The immunohistochemical OATP8 expression decreased from low-grade DNs to poorly differentiated HCCs (P < 0.0001, R = 0.15).ConclusionsThe immunohistochemical expression of OATP8 significantly decreases during multistep hepatocarcinogenesis, which may explain the decrease in enhancement ratio on gadoxetic acid-enhanced MR imaging.


Radiology | 2012

Hypervascular Hepatocellular Carcinoma: Correlation between Biologic Features and Signal Intensity on Gadoxetic Acid–enhanced MR Images

Azusa Kitao; Osamu Matsui; Norihide Yoneda; Kazuto Kozaka; Satoshi Kobayashi; Wataru Koda; Toshifumi Gabata; Tatsuya Yamashita; Shuichi Kaneko; Yasuni Nakanuma; Ryuichi Kita; Shigeki Arii

PURPOSE To analyze the correlation among biologic features, tumor marker production, and signal intensity at gadoxetic acid-enhanced MR imaging in hepatocellular carcinomas (HCCs). MATERIALS AND METHODS Institutional ethics committee approval and informed consent were obtained for this retrospective study. From April 2008 to September 2011, 180 surgically resected HCCs in 180 patients (age, 65.0 years ± 10.3 [range, 34-83 years]; 138 men, 42 women) were classified as either hypointense (n = 158) or hyperintense (n = 22) compared with the signal intensity of the background liver on hepatobiliary phase gadoxetic acid-enhanced MR images. Pathologic features were analyzed and a fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) production were compared by means of serum analysis and immunohistochemical staining. Recurrence and survival rates were also evaluated. The Mann-Whitney and Pearson correlation tests were used for statistical analysis. RESULTS The grade of differentiation was higher (P = .028) and portal vein invasion was less frequent in hyperintense HCCs (13.6%) than in hypointense HCCs (36.7%) (P = .039). The serum levels of AFP, Lens culinaris agglutinin reactive fraction of AFP, and PIVKA-II were lower in hyperintense than in hypointense HCCs (P = .003, .004, and .026, respectively). Immunohistochemical AFP and PIVKA-II expression were lower in hyperintense than in hypointense HCCs (both P < .001). The recurrence rate was lower in hyperintense than in hypointense HCCs (P = .039). CONCLUSION The results suggest that hyperintense HCCs on gadoxetic acid-enhanced MR images are less aggressive than hypointense HCCs. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120226/-/DC1.


European Journal of Radiology | 2012

Relationship between signal intensity on hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MR imaging and prognosis of borderline lesions of hepatocellular carcinoma

Satoshi Kobayashi; Osamu Matsui; Toshifumi Gabata; Wataru Koda; Tetsuya Minami; Yasuji Ryu; Kazuto Kozaka; Azusa Kitao

PURPOSE To elucidate the incidence of signal intensity patterns of borderline lesions of hepatocellular carcinoma (HCC) on hepatobiliary phase Gd-EOB-DTPA (EOB) enhanced MRI and clarify the natural histories of these lesions. MATERIALS AND METHODS Total 99 borderline lesions of HCC were identified by angiography-assisted CT. The signal intensity of borderline lesions on hepatobiliary phase of EOB-enhanced MRI was analyzed. Progress rate from borderline lesions to hypervascular HCC was calculated with the Kaplan-Meier method among each signal intensity groups of nodules. RESULTS On hepatobiliary phase of EOB-enhanced MRI, 41.4% of the borderline lesions showed hypo-, 42.4% showed iso-, and 16.2% showed hyperintense, compared to background liver. Overall progress rates from borderline lesions to HCC were 10% in 1-year, 14% in 2-year and 20% in 3-year follow-up period. Progress rates to HCC in hypointense borderline lesions were 17% in 1-year, 28% in 2-year and 41% in 3-year follow-up period, and in isointense borderline lesions were 7% in 1-year, 7% in 2-year and 7% in 3-year follow-up period. No hyperintense borderline lesions progressed to HCC in follow-up period. CONCLUSION Although borderline lesions of HCC may show hypo-, iso- and hyperintensity on hepatobiliary phase of EOB-enhanced MRI, hypointense borderline lesions are high risk to progress HCC.


Laboratory Investigation | 2000

Evidence of the participation of peribiliary mast cells in regulation of the peribiliary vascular plexus along the intrahepatic biliary tree.

Wataru Koda; Kenichi Harada; Koichi Tsuneyama; Naoko Kono; Motoko Sasaki; Osamu Matsui; Yasuni Nakanuma

Our pilot study disclosed that tryptase-positive mast cells (MC) were densely distributed around the intrahepatic bile ducts (peribiliary MC). In this study, the pathophysiologic roles of these MC were examined with respect to the microcirculation around the bile duct in 71 cases of histologically normal liver, 24 cases of chronic hepatitis, and 45 cases of liver cirrhosis. The tryptase-positive MC were very close to the microvessels of the peribiliary vascular plexus (PVP), which supply the intrahepatic biliary tree. The tryptase-positive MC were frequently found adjacent to vascular smooth muscle cells, including pericytes. The location of the tryptase-positive MC was confirmed by ultrastructural analysis. In cirrhosis, the numbers of both microvessels of PVP and peribiliary MC increased in parallel. Peribiliary MC were immunoreactive for endothelin 1 (ET-1), and were variably immunoreactive for histamine, chymase, inducible nitric oxide synthase (iNOS), and endothelin A and B (ETA and ETB) receptors, particularly in cirrhotic livers. On vascular endothelial cells of PVP, endothelial nitric oxide synthase (eNOS) and ET-1 were consistently detectable, and ETA receptors, ETB receptors, and iNOS were variably detectable. Pericytes of PVP expressed ETA and ETB receptors in addition to ET-1 and iNOS. Biliary epithelial cells also focally expressed iNOS, ET-1, and ETA and ETB receptors. These vasoactive substances were strongly expressed on the cellular components in cirrhotic liver. By in situ hybridization, iNOS mRNA signals were observed on iNOS-immunoreactive cell components, including peribiliary MC. These morphologic and immunohistochemical findings suggest that the cellular components displaying vasoactive substances in the milieu of the intrahepatic biliary tree are very dynamic in the vasoregulation of PVP in normal livers, even more so in cirrhosis, and that peribiliary MC exert local effects on the microcirculation of PVP, directly and indirectly. A list of abbreviations: AMeX, acetone, methyl benzoate, and xylene; ASMA, α-smooth muscle actin; ET, endothelin; ET-1, endothelin 1; ETA receptor, endothelin A receptor; ETB receptor, endothelin B receptor; eNOS, endothelial nitric oxide synthase; MC, mast cell; MCT, tryptase positive, chymase negative mast cells; MCTC, tryptase positive, chymase positive mast cells; NO, nitric oxide; iNOS, inducible nitric oxide synthase; PBS, phosphate buffer saline; PVP, peribiliary vascular plexus; TNF-, tumor necrosis factor α


Journal of Computer Assisted Tomography | 2011

Gadolinium ethoxybenzyl diethylenetriamine pentaacetic Acid-enhanced magnetic resonance imaging findings of borderline lesions at high risk for progression to hypervascular classic hepatocellular carcinoma.

Satoshi Kobayashi; Osamu Matsui; Toshifumi Gabata; Wataru Koda; Tetsuya Minami; Yasuji Ryu; Keiichi Kawai; Kazuto Kozaka

Objectives: The objectives of the study were to assess the imaging features of hypovascular borderline lesions containing hypervascular foci on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and to evaluate the ability of Gd-EOB-DTPA-enhanced MRI to diagnose high-risk borderline lesions possibly consistent with early hepatocellular carcinoma (HCC). Methods: Institutional review board approval was obtained for this retrospective analysis of imaging findings, and informed consent was obtained from 217 consecutive patients undergoing Gd-EOB-DTPA-enhanced MRI and angiography-assisted computed tomography (CT) for examination of hepatocellular nodular lesions in cirrhotic livers. There were 73 nodules showing hypervascular foci in borderline lesions identified by angiography-assisted CT. Signal intensity patterns of the nodules were evaluated on hepatobiliary-phase Gd-EOB-DTPA-enhanced T1-weighted MRI obtained 20 minutes after intravenous injection of contrast media. Results: Among 73 high-risk borderline lesions, 59 were hypointense (81%), and 14 were isointense (19%), compared with background liver parenchyma. There were 27 untreated lesions followed by CT and/or MRI. Almost half of these nodules transformed into hypervascular HCC, regardless of signal intensities seen on hepatobiliary-phase Gd-EOB-DTPA-enhanced MRI. Conclusions: Although many high-risk borderline HCC lesions are hypointense on hepatobiliary-phase Gd-EOB-DTPA-enhanced MRI, some high-risk borderline lesions are isointense and transform at the same rate into hypervascular HCC.


Journal of Vascular and Interventional Radiology | 2001

Use of a catheter with a large side hole for selective catheterization of the inferior phrenic artery.

Shiro Miyayama; Osamu Matsui; Yukari Akakura; Toru Yamamoto; Yasunari Fujinaga; Wataru Koda; Keiichi Kawai; Kazuo Notsumata; Daisyu Toya; Nobuyoshi Tanaka

The authors report the use of a catheter with a large side hole in the catheterization of the right inferior phrenic artery (IPA) arising from the proximal portion of the celiac trunk. A 5-F catheter with a side hole on either the top or the right side of the superior portion near the tip was used in five patients with hepatocellular carcinoma fed by the right IPA, which could not be selected by a conventional coaxial technique. In all patients, a 3-F microcatheter was successfully advanced into the right IPA through the side hole of this catheter introduced into the celiac artery or the common hepatic artery.


Histopathology | 2000

Distribution of apoptotic cells and expression of apoptosis-related proteins along the intrahepatic biliary tree in normal and non-biliary diseased liver

Kenichi Harada; Mitsuhiro Iwata; Naoko Kono; Wataru Koda; Tomonori Shimonishi; Yasuni Nakanuma

Aims


European Journal of Radiology | 2012

Intranodular signal intensity analysis of hypovascular high-risk borderline lesions of HCC that illustrate multi-step hepatocarcinogenesis within the nodule on Gd-EOB-DTPA-enhanced MRI

Satoshi Kobayashi; Osamu Matsui; Toshifumi Gabata; Wataru Koda; Tetsuya Minami; Yasuji Ryu; Kazuto Kozaka; Azusa Kitao

OBJECTIVES To analyze intranodular signal intensity pattern of hypovascular high-risk borderline lesions of HCC that illustrate multi-step hepatocarcinogenesis within the nodule on Gd-EOB-DTPA-enhanced MRI. METHODS A total of 73 nodules showing hypervascular foci in hypovascular high-risk borderline lesions identified by angiography-assisted CT were included in this study. The intranodular signal intensities of both the hypervascular foci and the hypovascular high-risk borderline lesions were evaluated on hepatobiliary-phase EOB-enhanced MRI obtained 20 min after intravenous injection of contrast media. RESULTS Among 59 hypervascular foci within hypointense hypovascular high-risk borderline lesions, 6 showed more hypointensity, 32 isointensity, and 21 hyperintensity compared to the surrounding hypointense, hypovascular portion of the nodules. Among 14 hypervascular foci within isointense hypovascular high-risk borderline lesions, 5 showed isointensity, and 9 hypointensity compared to the surrounding isointense hypovascular high-risk borderline lesions. No hypervascular foci showed hyperintensity compared to the surrounding isointense hypovascular high-risk borderline lesions. CONCLUSIONS In most of the hypovascular high-risk borderline lesions containing hypervascular foci within the nodule, the signal intensity was decreased in hypervascular foci as compared with hypovascular high-risk borderline lesions and the surrounding background liver parenchyma. This supports the concept of signal intensity decrease during the dedifferentiation process in multistep hepatocarcinogenesis. However, around 30% of the nodules did not follow this rule, and hypervascular foci showed hyperintensity relative to the hypovascular high-risk borderline lesions.


Radiology | 2015

Hepatocellular Carcinoma with β-Catenin Mutation: Imaging and Pathologic Characteristics.

Azusa Kitao; Osamu Matsui; Norihide Yoneda; Kazuto Kozaka; Satoshi Kobayashi; Junichiro Sanada; Wataru Koda; Tetsuya Minami; Dai Inoue; Kotaro Yoshida; Taro Yamashita; Tatsuya Yamashita; Shuichi Kaneko; Hiroyuki Takamura; Tetsuo Ohta; Hiroko Ikeda; Yasuni Nakanuma; Ryuichi Kita; Toshifumi Gabata

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.

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