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| 1 | Pathological classification of intrahepatic cholangiocarcinoma based on a new concept显示文摘Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma.Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC. | Yasuni Nakanuma Yasunori Sato Kenichi Harada Mokoto Sasaski Hiroko Ikeda | 2010 | World Journal of Hepatology2010，2，12： | 34 |
| 2 | Intraductal papillary neoplasm of the bile duct in liver cirrhosis with hepatocellular carcinoma显示文摘A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported. A 76-year-old man was admitted to our hospital with recurrent HCC. Laboratory data showed that levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were elevated. He died of progressive hepatic failure. At autopsy,in addition to HCCs,an intraductal papillary proliferation of malignant cholangiocytes with fibrovascular cores was found in the dilated large bile ducts in the left lobe,and this papillary carcinoma was associated with an invasive mucinous carcinoma (invasive IPNB). Interestingly,extensive intraductal spread of the cholangiocarcinoma was found from the reactive bile ductular level to the interlobular bile ducts and septal bile ducts and to the large bile ducts in the left lobe. Neural cell adhesion molecule,a hepatic progenitor cell marker,was detected in IPNB cells. It seems possible in this case that hepatic progenitor cells located in reactive bile ductules in liver cirrhosis may have been responsible for the development of the cholangiocarcinoma and HCC,and that the former could have spread in the intrahepatic bile ducts and eventually formed grossly visible IPNB. | Jing Xu Yasunori Sato Kenichi Harada Norihide Yoneda Yasuni Nakanuma Teruyuki Ueda Atsushi Kawashima Akishi Ooi | 2011 | World Journal of Gastroenterology2011，17，14： | 4 |
| 3 | Tumorigenesis and phenotypic characteristics of mucin-producing bile duct tumors: an immunohistochemical approach显示文摘 | Yasuni Nakanuma Yoh Zen Kenichi Harada Hiroko Ikeda Yasunori Sato Takeshi Uehara Motoko Sasaki | 2010 | Journal of Hepato - Biliary - Pancreatic Sciences2010，，3： | 3 |
| 4 | Participation of peribiliary glands in biliary tract pathophysiologies显示文摘AIM:To investigate the roles of peribiliary glands around the bile ducts in the pathophysiology of the biliary tract.METHODS:The expression of fetal pancreatic markers,pancreatic duodenal homeobox factor 1(PDX1)and hairy and enhancer of split 1(HES1)and endodermal stem/progenitor(S/P)cell markers[CD44s,chemokine receptor type 4(CXCR4),SOX9 and epithelial cell adhesion molecule(EpCAM)]were examined immunohistochemically in 32 normal adult livers(autopsy livers)and 22 hepatolithiatic livers(surgically resected livers).The latter was characterized by the proliferation of the peribiliary glands.Immunohistochemistry was performed using formalin-fixed,paraffin-embedded tissue sections after deparaffinization.Although PDX1and HES1 were expressed in both the nucleus and cytoplasm of epithelial cells,only nuclear staining was evaluated.SOX9 was expressed in the nucleus,while CD44s,CXCR4 and EpCAM were expressed in the cell membranes.The frequency and extent of the expression of these molecules in the lining epithelia and peribiliary glands were evaluated semi-quantitatively based on the percentage of positive cells:0,1+(focal),2+(moderate)and 3+(extensive).RESULTS:In normal livers,PDX1 was infrequently expressed in the lining epithelia,but was frequently expressed in the peribiliary glands.In contrast,HES1was frequently expressed in the lining epithelia,but its expression in the peribiliary glands was focal,suggesting that the peribiliary glands retain the potential of differentiation toward the pancreas and the lining epithelia exhibit properties to inhibit such differentiation.This unique combination was also seen in hepatolithiatic livers.The expression of endodermal S/P cell markers varied in the peribiliary glands in normal livers:SOX9 and EpCAM were frequently expressed,CD44s infrequently,and CXCR4 almost not at all.The expression of these markers,particularly CD44s and CXCR4,increased in the peribiliary glands and lining epithelia in hepatolithiatic livers.This increased expression of endodermal S/P cell markers may be related to the increased production of intestinal and gastric mucin and also to the biliary neoplasia associated with the gastric and intestinal phenotypes reported in hepatolithiasis.CONCLUSION:The unique expression pattern of PDX1and HES1 and increased expression of endodermal S/P cell markers in the peribiliary glands may be involved in biliary pathophysiologies. | Saya Igarashi Yasunori Sato Xiang Shan Ren Kenichi Harada Motoko Sasaki Yasuni Nakanuma | 2013 | World Journal of Hepatology2013，5，8： | 3 |
| 5 | 帮助, P53,和 Mlh1 蛋白质在的表示内视镜地 resected 区分类型的早胃的癌症显示文摘 AIM: To analyze the expression of the tumor-related proteins in differentiated-type early gastric carcinoma (DEGC) samples. METHODS: Tumor specimens were obtained from 102 patients (75 males and 27 females) who had received an endoscopic tumor resection at Tottori University Hospital between 2007 and 2009. Ninety-one cancer samples corresponded to noninvasive or intramucosal carcinoma according to the Vienna classification system, and 11 samples were submucosal invasive carcinomas. All of the EGCs were histologically differenti- ated carcinomas. All patients were classified as having Helicobacter pylori (H. pylori ) infections by endoscopic atrophic changes or by testing seropositive for H. pylori IgG. All of the samples were histopathologically classified as either tubular or papillary adenocarcinoma according to their structure. The immunohistochemi- cal staining was performed in a blinded manner with respect to the clinical information. Two independent observers evaluated protein expression. All data were statistically analyzed then. RESULTS: The rates of aberrant activation-induced cytidine deaminase (AID) expression and P53 overexpression were both 34.3% in DEGCs. The expression of Mlh1 was lost in 18.6% of DEGCs. Aberrant AID expression was not significantly associated with P53 overexpression in DEGCs. However, AID expression was associated with the severity of mononuclear cell activity in the non-cancerous mucosa adjacent to the tumor (P = 0.064). The rate of P53 expression was significantly greater in flat or depressed tumors than in elevated tumors. The frequency of Mlh1 loss was significantly increased in distal tumors, elevated gross-type tumors, papillary histological-type tumors, and tumors with a severe degree of endoscopic atrophic gastritis (P < 0.05). CONCLUSION: Aberrant AID expression, P53 overexpression, and the loss of Mlh1 were all associated with clinicopathological features and gastric mucosal alterations in DEGCs. The aberrant expression of AID protein may partly contribute to the induction of nuclear P53 expression. | Yohei Takeda Kazuo Yashima Akihiro Hayashi Shuji Sasaki Koichiro Kawaguchi Kenichi Harada Yoshikazu Murawaki Hisao Ito | 2012 | World Journal of Gastrointestinal Oncology2012，4，6： | 2 |
| 6 | Intraductal papillary neoplasm of the bile duct accompanying biliary mixed adenoneuroendocrine carcinoma显示文摘We present the first case of an intraductal papillary neoplasm of the bile duct(IPNB) accompanying a mixed adenoneuroendocrine carcinoma(MANEC).A 74-yearold woman presented with fever of unknown cause.Laboratory data revealed jaundice and liver injury.Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct,which exhibited early enhancement and papillary growth.Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater,characterized by its protruding and dilated orifice.Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct,but no invasive region was suggested by diagnostic imaging.Therefore,the initial diagnosis was IPNB.After endoscopic nasobiliary drainage,a pylorus-preserving pancreaticoduodenectomy was performed.Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia,indicating pancreaticobiliary-type IPNB.In addition,solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident.Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component,diagnosing it as a neuroendocrine tumor(NET).Furthermore,the MIB-1 proliferation index of NET was higher than that of IPNB,and microinvasion of the NET component was found,indicating neuroendocrine carcinoma(NET G3).This unique case of MANEC,comprising IPNB and NET,provides insight into the pathogenesis of biliary NET. | Ichiro Onishi Hirohisa Kitagawa Kenichi Harada Syogo Maruzen Seisyo Sakai Isamu Makino Hironori Hayashi Hisatoshi Nakagawara Hidehiro Tajima Hiroyuki Takamura Takashi Tani Masato Kayahara Hiroko Ikeda Tetsuo Ohta Yasuni Nakanuma | 2013 | World Journal of Gastroenterology2013，19，20： | 2 |
| 7 | Characterization of non-small-cell lung cancer cell lines established before and after chemotherapy显示文摘 | Haruyuki Kawai Katsuyuki Kiura Masahiro Tabata Tadashi Yoshino Ichiro Takata Akio Hiraki Kenichi Chikamori Hiroshi Ueoka Mitsune Tanimoto Mine Harada | 2002 | Lung Cancer2002，，3： | 2 |
| 8 | Evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems显示文摘 | Yuko Kakuda Kenichi Harada Seiko Sawada-Kitamura Hiroko Ikeda Yasunori Sato Motoko Sasaki Hirofumi Okafuji Eishiro Mizukoshi Shuichi Terasaki Hajime Ohta Satomi Kasashima Atsuhiro Kawashima Yasuharu Kaizaki Shuichi Kaneko Yasuni Nakanuma | 2013 | Human Pathology2013，，6： | 2 |
| 9 | Adult case of an omphalomesenteric cyst resected by laparoscopic-assisted surgery显示文摘这份报告由帮助 laparoscopic 的外科描述脐肠系膜包囊 resected 的一个极其稀罕的成年案例。A 29-years-old 日语人被提交并且因为一个腹的团和提高的浆液 CEA (carcinoembryonic 抗原) ,承认了到九州大学医院在 2001 年 8 月的水平(21.3 ng/mL ) 。腹的 CT 和美国与中隔和石灰化表明了一个膀胱的团。腹腔镜检查显示了一个大团被纳入他的腹壁,测量 110 公里 x 70 公里 x 50 公里并且充满了粘液。团是由帮助 laparoscopic 的外科的 resected。它的墙的组织检查所见显示出纤维肌性织物,脂肪组织,石灰化,和肠的结构。是脐肠系膜包囊最后被诊断。 | Fumi Sawada Rie Yoshimura Kenichi Ito Kazuhiko Nakamura Hajime Nawata Kazuhiro Mizumoto Shuji Shimizu Takahiro Inoue Takashi Yao Masazumi Tsuneyoshi Atushi Kondo Naohiko Harada | 2006 | World Journal of Gastroenterology2006，12，5： | 2 |
| 10 | Pathology and pathogenesis of intrahepatic bile duct loss显示文摘 | Yasuni Nakanuma Koichi Tsuneyama Kenichi Harada | 2001 | Journal of Hepato - Biliary - Pancreatic Surgery2001，，4： | 1 |
| 11 | Separation of spiramycin components using high-speed chromatography 显示文摘 | OKA Hisao HARADA Kenichi SUZUKI Masanao | 2000 | Journal of Chromatography A2000，903，12： | 1 |
| 12 | Tumorigenesis and phenotypic characteristics of mucin-producing bile duct tumors: an immunohistochemical approach显示文摘 | Yasuni Nakanuma Yoh Zen Kenichi Harada Hiroko Ikeda Yasunori Sato Takeshi Uehara Motoko Sasaki | 2010 | Journal of Hepato - Biliary - Pancreatic Sciences2010，，3： | 1 |
| 13 | Helicobacter Genus DNA Fragments Are Commonly Detectable in Bile from Patients with Extrahepatic Biliary Diseases and Associated with Their Pathogenesis显示文摘 | Takashi Kobayashi MD Kenichi Harada MD PhD Koichi Miwa MD PhD Yasuni Nakanuma MD PhD | 2005 | Digestive Diseases and Sciences2005，，5： | 1 |
| 14 | Clinicopathological study of primary biliary cirrhosis with nterface hepatitis compared to autoimmune hepatitis显示文摘AIM:To investigate histological and immunohistochemical differences in hepatitis between autoimmune hepatitis(AIH)and primary biliary cirrhosis(PBC)with AIH features.METHODS:Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were examined.The activity of periportal and lobular inflammation was scored0(none or minimal activity)to 4(severe),and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored 0-3.The infiltration of mononuclear cells positive for CD20,CD38,CD3,CD4,and CD8 and positive for immunoglobulins(IgG,IgM,and IgA)at the periportal areas(interface hepatitis)and in the hepatic lobules(lobular hepatitis)were semiquantitatively scored in immunostained liver sections(score 0-6).Serum aspartate aminotransferase(AST),immunoglobulins,and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual lesions.RESULTS:Lobular hepatitis,hepatitic rosette formation,and emperipolesis were more extensive and frequent in AIH than in PBC.CD3+,CD4+,and CD8+cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in PBC.The degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC,but to a lesser degree in AIH.CD20+cells were mainly found in the portal tracts and,occasionally,at the interface in both diseases.Elevated AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration,specifically CD38+cells in PBC.No correlation existed between autoantibodies and inflammatory cell infiltration in PBC or AIH.While most AIH cases were IgG-predominant at the interface,PBC cases were divided into IgM-predominant,IgM/IgGequal,and IgG-predominant types,with the latter sharing several features with AIH.CONCLUSION:These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical. | Mio Kobayashi Yuko Kakuda Kenichi Harada Yasunori Sato Motoko Sasaki Hiroko Ikeda Mitsuhiro Terada Munenori Mukai Shuichi Kaneko Yasuni Nakanuma | 2014 | World Journal of Gastroenterology2014，20，13： | 1 |
| 15 | Clerodane Diterpenoid with NGF-Potentiating Activity from Ptychopetalum olacoides显示文摘 | Tang Wanxia Hideaki Hioki Kenichi Harada | | 0，，： | 1 |
| 16 | Novel NGF-Potentiating Diterpenoids from a Brazilian medicinal plant,Ptychopetalum olacoides显示文摘 | Tang Wanxia Miwa Kubo Kenichi Harada | | 0，，： | 1 |
| 17 | Endothelial to Mesenchymal Transition via Transforming Growth Factor-β1/Smad Activation Is Associated with Portal Venous Stenosis in Idiopathic Portal Hypertension显示文摘 | Azusa Kitao Yasunori Sato Seiko Sawada-Kitamura Kenichi Harada Motoko Sasaki Hiroyasu Morikawa Susumu Shiomi Masao Honda Osamu Matsui Yasuni Nakanuma | 2009 | The American Journal of Pathology2009，，2： | 1 |
| 18 | Eight New Clerodane Diterpenoid from the Bark of Ptychopetalum olacoides显示文摘 | Tang Wanxia Kenichi Harada Miwa Kubo | | 0，，03： | 1 |
| 19 | Anatomic and molecular pathology of intrahepatic cholangiocarcinoma显示文摘 | Yasuni Nakanuma Kenichi Harada Akira Ishikawa Yoh Zen Motoko Sasaki | 2003 | Journal of Hepato - Biliary - Pancreatic Surgery2003，，4： | 1 |
| 20 | Clinicopathologic Significance of Combined Hepatocellular-Cholangiocarcinoma With Stem Cell Subtype Components With Reference to the Expression of Putative Stem Cell Markers显示文摘 | Hiroko Ikeda Kenichi Harada Yasunori Sato Motoko Sasaki Norihide Yoneda Seiko Kitamura Yoshiko Sudo Akishi Ooi Yasuni Nakanuma | 2013 | American Journal of Clinical Pathology2013，，3： | 1 |
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