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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 | Enhancement patterns of pancreatic adenocarcinoma on conventional dynamic multi-detector row CT:Correlation with angiogenesis and fibrosis显示文摘AIM:To evaluate retrospectively the correlation between enhancement patterns on dynamic computed tomography (CT) and angiogenesis and fibrosis in pancreatic adenocarcinoma.METHODS: Twenty-three patients with pancreatic adenocarcinoma underwent dynamic CT and tumor resection. In addition to the absolute and relative enhanced value that was calculated by subtracting the attenuation value on pre-contrast from those on contrast-enhanced CT in each phase, we defined one parameter, 'tumor-aorta enhancement ratio', which was calculated by dividing enhancement of pancreatic cancer by enhancement of abdominal aorta in each phase. These enhancement patterns were correlated with the level of vascular endothelial growth factor (VEGF), microvessel density (MVD), and extent of fibrosis.RESULTS: The absolute enhanced value in the arterial phase correlated with the level of VEGF and MVD (P=0.047, P=0.001). The relative enhanced value in arterial phase and tumor-aorta enhancement ratio (arterial) correlated with MVD (P=0.003, P=0.022). Tumor-aorta enhancement ratio (arterial) correlated negatively with the extent of fibrosis (P=0.004). The tumors with greater MVD and higher expression of VEGF tended to show high enhancement in the arterial dominant phase. On the other hand, the tumors with a larger amount of fibrosis showed a negative correlation with the grade of enhancement during the arterial phase.CONCLUSION: Enhancement patterns on dynamic CT correlated with angiogenesis and may be modified by the extent of fibrosis. | Yuki Hattori Toshifumi Gabata Osamu Matsui Kentaro Mochizuki Hirohisa Kitagawa Masato Kayahara Tetsuo Ohta Yasuni Nakanuma | 2009 | World Journal of Gastroenterology2009,15,25: | 15 |
| 3 | Characterization of CD133^+ parenchymal cells in the liver:Histology and culture显示文摘AIM:To reveal the characteristics of CD133+ cells in the liver.METHODS:This study examined the histological characteristics of CD133+ cells in non-neoplastic and neoplastic liver tissues by immunostaining,and also analyzed the biological characteristics of CD133+ cells derived from human hepatocellular carcinoma(HCC) or cholangiocarcinoma cell lines.RESULTS:Immunostaining revealed constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium,and these cells had the immunophenotype CD133+/CK19+/HepPar-1-.A small number of CD133+/CK19-/HepPar-1+ cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma.In addition,small ductal structures,resembling the canal of Hering,partly surrounded by hepatocytes were positive for CD133.CD133 expression was observed in three HCC(HuH7,PLC5 and HepG2) and two cholangiocarcinoma cell lines(HuCCT1 and CCKS1).Fluorescence-activated cell sorting(FACS) revealed that CD133+ and CD133-cells derived from HuH7 and HuCCT1 cells similarly produced CD133+ and CD133-cells during subculture.To examine the relationship between CD133+ cells and the side population(SP) phenotype,FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133.The ratios of CD133+/CD133-cells were almost identical in the SP and non-SP in HuH7.In addition,four different cellular populations(SP/CD133+,SP/CD133-,non-SP/CD133+,and non-SP/CD133-) could similarly produce CD133+ and CD133-cells during subculture.CONCLUSION:This study revealed that CD133 could be a biliary and progenitor cell marker in vivo.However,CD133 alone is not sufficient to detect tumor-initiating cells in cell lines. | Seiichi Yoshikawa Yoh Zen Takahiko Fujii Yasunori Sato Tetsuo Ohta Yutaka Aoyagi Yasuni Nakanuma | 2009 | World Journal of Gastroenterology2009,15,39: | 6 |
| 4 | Prospective Cohort Study of Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma in 8510 Patients显示文摘 | Kenichi Takayasu Shigeki Arii Iwao Ikai Masao Omata Kiwamu Okita Takafumi Ichida Yutaka Matsuyama Yasuni Nakanuma Masamichi Kojiro Masatoshi Makuuchi Yoshio Yamaoka | 2006 | Gastroenterology2006,,2: | 5 |
| 5 | 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 |
| 6 | 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 |
| 7 | Primary localized malignant biphasic mesothelioma of the liver in a patient with asbestosis显示文摘We report a case of primary localized malignant biphasic mesothelioma of the liver in a 66-year-old man associated with asbestosis. The tumor was detected as a hepatic nodule, 4 cm in diameter, in the right lobe (S8 segment) on CT scan. Histopathological examination demonstrated an intrahepatic tumor with central necrosis consisting of a papillary epithelioid pattern on the surface of the liver, microcystic (microglandular or adenomatoid) pattern mainly in the subcapsular area and sarcomatoid pattern intermingled with microcystic pattern in the major part of the hepatic nodular tumor. Tumor cells, especially of epithelioid type, showed distinct immunoreactivity for mesothelial markers (WT-1, calretinin, D2-40, CK5/6, mesothelin, thrombomodulin) and no immunoreactivity for epithelial (adenocarcinoma) markers (CEA, CD15, BerEP4, BG8, MOC31). P53 immunoreactivity was detected focally in papillary epithelioid tumor cells and extensively in microcystic and sarcomatoid components, suggesting that the papillary epithelioid mesothelioma arose on the surface of the liver, and tumor cells showing microcystic and sarcomatoid patterns invaded and grew into the liver. To date, this is the first case of primary localized malignant biphasic mesothelioma of the liver, since all three primary hepatic mesotheliomas reported so far were epithelioid type. | Motoko Sasaki Ichiro Araki Toshiaki Yasui Masaru Kinoshita Keita Itatsu Takayuki Nojima Yasuni Nakanuma | 2009 | World Journal of Gastroenterology2009,15,5: | 3 |
| 8 | 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 |
| 9 | Intraductal papillary neoplasia of the liver associated with hepatolithiasis显示文摘 | Tse-Ching Chen Yasuni Nakanuma Yoh Zen Miin-Fu Chen Yi-Yin Jan Ta-Sen Yeh Cheng Tang Chiu Tseng-Tong Kuo Jun-ichi Kamiya Koji Oda Michinari Hamaguchi Yoshiyuki Ohno Ling-Ling Hsieh Yuji Nimura | 2001 | Hepatology2001,,4: | 2 |
| 10 | 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 |
| 11 | 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 |
| 12 | Report of the 15th follow-up survey of primary liver cancer显示文摘 | Iwao Ikai Yuji Itai Kiwamu Okita Masao Omata Masamichi Kojiro Kenichi Kobayashi Yasuni Nakanuma Shunji Futagawa Masatoshi Makuuchi Yoshio Yamaoka | 2003 | Hepatology Research2003,,1: | 2 |
| 13 | Are hepatolithiasis and cholangiocarcinoma aetiologically related?显示文摘 | Yasuni Nakanuma Tadashi Terada Yoshinori Tanaka Goroku Ohta | 1985 | Virchows Archiv A Pathological Anatomy and Histopathology1985,,1: | 2 |
| 14 | Precancerous lesions of intrahepatic cholangiocarcinoma显示文摘 | Tomonori Shimonishi Motoko Sasaki Yasuni Nakanuma | 2000 | Journal of Hepato - Biliary - Pancreatic Surgery2000,,6: | 1 |
| 15 | 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 |
| 16 | IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung显示文摘 | Yoh Zen Satoshi Kitagawa Hiroshi Minato Hiroshi Kurumaya Kazuyoshi Katayanagi Shinji Masuda Hideki Niwa Masaki Fujimura Yasuni Nakanuma | 2005 | Human Pathology2005,,7: | 1 |
| 17 | Expression profiles of MUC mucin core protein in the intrahepatic biliary system: physiological distributeon and pathologyical significance显示文摘 | Motoko Sasaki Hiroko Ikeda Yasuni Nakanurna | 2005 | Acta Histochemm Cytochem2005,38,5: | 1 |
| 18 | Prospective Cohort Study of Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma in 8510 Patients显示文摘 | Kenichi Takayasu Shigeki Arii Iwao Ikai Masao Omata Kiwamu Okita Takafumi Ichida Yutaka Matsuyama Yasuni Nakanuma Masamichi Kojiro Masatoshi Makuuchi Yoshio Yamaoka | 2006 | Gastroenterology2006,,2: | 1 |
| 19 | Enhanced Self-Renewal Capability in Hepatic Stem/Progenitor Cells Drives Cancer Initiation显示文摘 | Tetsuhiro Chiba Yun-Wen Zheng Kaoru Kita Osamu Yokosuka Hiromitsu Saisho Masafumi Onodera Hiroyuki Miyoshi Masayuki Nakano Yoh Zen Yasuni Nakanuma Hiromitsu Nakauchi Atsushi Iwama Hideki Taniguchi | 2007 | Gastroenterology2007,,3: | 1 |
| 20 | 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 |