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Jing Xu,
Saya Igarashi,
Motoko Sasaki,
Takashi Matsubara,
Norihide Yoneda,
Kazuto Kozaka,
Hiroko Ikeda,
Jihun Kim,
Eunsil Yu,
Osamu Matsui,
Yasuni Nakanuma
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ABSTRACT: Intrahepatic cholangiocarcinomas (ICCs) are usually adenocarcinomas with fibrotic and hypovascular stroma. Intrahepatic cholangiocarcinomas in cirrhosis and precirrhotic liver (ICC-cirrhosis) are increasingly being diagnosed, and can display hypervascular enhancement resembling a hepatocellular carcinoma on dynamic imaging.
In this study using ICC-cirrhosis (71 cases), ICC with non-specific reactive changes (ICC-reactive) (72 cases) and the cholangiocarcinoma component of combined hepatocellular cholangiocarcinoma (HCC-ICC) (30 cases), we tried to compare the tumour vasculature.
It was found that ICC-cirrhosis and the cholangiocarcinoma component of HCC-ICC showed a higher density of arteries and microvessels (1.59 ± 0.58/mm(2) (mean ± SD) and 140 ± 43/mm(2) in ICC-cirrhosis and 1.74 ± 0.67/mm(2) and 131 ± 46/mm(2) in the cholangiocarcinoma component of HCC-ICC) than in ICC-reactive (1.26 ± 0.61/mm(2) and 103 ± 45/mm(2) ). Dynamic computed tomography (CT) and magnetic resonance imaging (MRI) showed that a majority of ICC-cirrhosis displayed strong hypervascular enhancement, whereas one-third of ICC-reactive each showed strong, weak and no or minimal enhancement respectively. The increased vascular density was positively correlated with enhanced arterial phase of dynamic CT and MRI.
The density of arteries and microvessels of ICC-cirrhosis was higher than that in ICC-reactive and comparable to that in the cholangiocarcinoma component of HCC-ICC, and the higher density of arteries and microvessels in ICC may be responsible for the hypervascular enhancement of ICC-cirrhosis.
Liver international: official journal of the International Association for the Study of the Liver 03/2012; 32(7):1156-64. · 3.82 Impact Factor
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ABSTRACT: Intrahepatic cholangiocarcinomas (ICCs) are known to arise in cases of non-biliary, chronic advanced liver disease (CALD), but their clinicopathological features remain unexplored. The aim of this study was to compare the histological and immunohistochemical ICCs arising inCALD with those arising in livers with non-specific reactive (NSR) changes.
Seventy-one cases of ICC arising in CALD were compared with ICCs arising in livers with NSR changes, including normal livers (72 cases) and the cholangiocarcinomatous (CC) component of hepatocellular cholangioncarcinomas (HC-CCs) (30 cases). The expression of mucin was higher in ICC with NSR changes, whereas it was relatively low in ICC with CALD and the CC component of HC-CC. The expression of biliary markers [cytokeratin (CK)7, CK19, epithelial membrane antigen, and epithelial cell adhesion molecule (EpCAM)] was lower in CC with CALD and in the CC component of HC-CC than in CC with NSR changes. The expression of hepatic progenitor cell markers [neural cell adhesion molecule (NCAM) and c-kit] was higher in ICC with CALD and the CC component of HC-CC than in ICC with NSR changes. EpCAM and CK19 were constantly expressed in cultured CC cells, whereas NCAM was infrequently expressed in cultured CC cells.
The carcinogenesis of ICC arising in CALD and the ICC component of HC-CC, each showing similar features, may involve hepatic progenitor cells.
Histopathology 12/2011; 59(6):1090-9. · 3.08 Impact Factor
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ABSTRACT: Intrahepatic cholangiocarcinoma (ICC) is reported to develop in non-biliary chronic advanced liver diseases (CALD). Herein, we characterize the pathological features of ICC arising in CALD in comparison with those in non-CALD livers. Of 471 surgically resected cases of ICC in Kanazawa, Japan and Seoul, Korea, 53 were associated with CALD (group A), while the remaining 418 arose in otherwise normal livers (group B). When ICC were classified into bile duct type, bile ductular type, variants, and intraductal papillary neoplasm of the bile duct (IPNB), the whole spectrum of subtypes were found in group A; the majority of ICC belonged to the bile duct type in both groups. In group A, bile ductular type was rather frequent (22.6%) compared with group B (8.4%). IPNB was more frequent in group B (22.5%) than group A (3.8%), and in group B, frequent in Seoul cases (24.8%), but rare in Kanazawa cases (2.3%). Variants of ICC were rare in both groups. These results imply that cholangiocarcinogenesis itself is upregulated in group A in comparison with group B and that the bile ductular type is specifically related to group A. Some unique environmental factors in Seoul may be responsible for the frequent development of IPNB.
Pathology International 05/2011; 61(5):298-305. · 1.62 Impact Factor
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ABSTRACT: 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.
World Journal of Gastroenterology 04/2011; 17(14):1923-6. · 2.47 Impact Factor
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ABSTRACT: Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic differentiation. To date, ICC was largely classified 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 open up a new field of research of ICC and contribute to the clinical approach to ICC.
World journal of hepatology. 12/2010; 2(12):419-27.