The etiopathogenesis of primary biliary cirrhosis (PBC) remains speculative. Epithelioid granulomas are often found in the vicinity of damaged interlobular bile ducts in PBC, raising the possibility of a reaction to microbial materials. In this study, we tried to detect and identify bacterial DNA within granulomatous lesions in PBC. Using liver sections from 9 patients with PBC and 13 control livers, granuloma in portal tracts, portal tracts without granuloma, and adjacent hepatic parenchyma were selectively microdissected from sections, and then DNA was extracted from them. First, part of the bacterial 16S ribosomal RNA (rRNA) gene was amplified from DNA samples extracted from 5 PBC and 6 control livers, and their amplicons were sequenced for the identification of bacterial species. Several indigenous bacteria were identified. Among them, Propionibacterium acnes (P. acnes) was detected as a major clone in 20% to 50% of sequenced clones from granuloma of PBC, but the detection rate of P. acnes was 0% to 20% in those cloned from adjacent hepatic parenchyma of PBC. Then, a P. acnes-specific PCR was performed using all microdissected samples. Distinct PCR products were identified in epithelioid granuloma in all 9 PBC cases. The result that P. acnes DNA is present as a major clone in granulomas of PBC, suggest that P. acnes is involved in the pathogenesis of granuloma in PBC. (HEPATOLOGY 2001;33: 530-536.)

Biliary cystadenocarcinoma with oncocytic differentiation was first reported in 1992. This is a report of a second case. The patient (a 71-year-old man) was admitted to our hospital complaining of abdominal fullness. Multicystic lesions were identified in the left hepatic lobe radiologically. The patient died of peritoneal dissemination of carcinoma 20 months later. At autopsy, the tumor of the left hepatic lobe was found to be composed of adjoining multiple cystic lesions and a solid lesion with infiltration of the hepatic hilus and peritoneal dissemination. Histologically, the multicystic lesions were covered by papillary neoplastic epithelial cells with an eosinophilic granular cytoplasm resembling that of oncocytes and a fine fibrovascular core. The cyst wall was fibrous, but there was no mesenchymal stroma. In the solid lesion and infiltrated areas, acidophilic and granular carcinoma cells formed small glandular or solid cord patterns with much mucin secretion (mucinous carcinoma). Immunohistochemically, carcinoma cells of both components were found to contain many mitochondria and showed the phenotypes of hepatocytes and cholangiocytes. Interestingly, the intrahepatic biliary tree also was invaded by carcinoma cells. This may be a case of intraductal oncocytic papillary neoplasm of the left hepatic lobe followed by secondary cystic dilatation of the affected bile duct.

Ultraselective TACE induces not only complete tumor necrosis but also peritumoral parenchymal necrosis, similar to that after radiofrequency ablation, when the portal veins are markedly visualized during the TACE procedure.

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Objectives: To examine the clinicopathologic features of combined hepatocellular-cholangiocarcinoma (HC-CC), which the World Health Organization (WHO) proposed classifying into 2 types, and the expression of delta-likeSeveral markers and approaches have been used to detect and characterize hepatic stem/progenitor cells. [2][3][4][5] For example, the simultaneous immunohistochemical expression of an HCC marker (HepPar1 or a-fetoprotein [AFP]) and a biliary marker (cytokeratin [CK] 19 or carcinoembryonic antigen) has been recommended for the identification of hepatic stem/ progenitor cells in nonneoplastic and neoplastic livers, and the expression of nuclear cell adhesion molecule (NCAM/ CD56) and epithelial cell adhesion molecule (EpCAM) has been reported in small and oval-shaped stem cell-like cells. [1][2][3][4][5] Delta-like 1 homolog (DLK1) has been reported to be a biomarker of hepatic stem/progenitor cells in murine liver, because DLK1 is expressed in fetal liver, but it is restricted to a subpopulation of oval/hepatic progenitor cells in adult liver. Moreover, purified DLK1-positive cells can differentiate into both hepatocyte and biliary epithelial lineages and repopulate the normal liver in vivo after transplantation. [6][7][8] The expression of DLK1 has been reported in human fetal liver but not in normal adult liver or diseased livers with viral hepatitis and cirrhosis. 9,10 However, upregulation of DLK1 expression recently Ikeda_2012100561.indd 329

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Serum antinuclear antibodies (ANA) are occasionally noted in the patients with non-alcoholic steatohepatitis (NASH). We examined the significance of ANA in NASH by comparing the clinicopathological features in the patients with ANA-positive NASH (n=35) and ANA-negative NASH (n=36). Inflammatory cell profiles and the distribution of oxidative stress markers were also examined immunohistochemically. The ANA-positive NASH was significantly associated with female gender (p= .005), high degree of portal inflammation (p= .039), interface activity (p= .036) and hepatocellular ballooning (p= .0008). In addition, The ANA of high-titer (320-fold or more) was significantly associated with the histological grade and stage of NASH (p= .02). The degree of steatosis is rather mild in high-titer ANA group (p= .01). The analysis of inflammatory cell profiles revealed that CD3-positive T cells were predominant and plasma cells were rather few in portal area and hepatic lobules in both ANA-positive and ANA-negative groups. There was no difference in the distribution of oxidative stress markers between ANA-positive and ANA-negative groups. These findings suggest that the presence of ANA may be related to the progression of NASH and that a different type of autoimmune mechanisms may be involved in the pathogenesis of NASH with ANA, compared to the pathogenesis of autoimmune hepatitis.