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ABSTRACT: α-Fetoprotein is expressed in hepatocellular carcinoma, yolk sac tumor, and some gastric carcinomas. The α-fetoprotein-producing gastric carcinoma composed of hepatoid and common adenocarcinoma shows morphological similarities to combined hepatocellular and cholangiocarcinoma. In this study, the expression of putative hepatic stem/progenitor markers (EpCAM, OV-6, DLK-1, and NCAM/CD56), hepatocyte markers (HepParI, α-fetoprotein, glypican 3), and the germ cell marker SALL4 was examined in α-fetoprotein-producing gastric carcinoma (20 cases) and combined hepatocellular and cholangiocarcinoma (20 cases) for evaluation of pathologic differentiation and also the histogenesis of both tumors. The SALL4 protein was expressed in 95% of α-fetoprotein-producing gastric carcinoma, including the hepatoid component (hepatoid gastric carcinoma), but was absent in combined hepatocellular and cholangiocarcinoma. Glypican 3 and α-fetoprotein were detected in all hepatoid-type α-fetoprotein-producing gastric carcinoma but variably in combined hepatocellular and cholangiocarcinoma. NCAM/CD56 was expressed focally in combined hepatocellular and cholangiocarcinoma but was rare in hepatoid gastric carcinoma. EpCAM, DLK-1, and OV6 were variably expressed in hepatoid gastric carcinoma and combined hepatocellular and cholangiocarcinoma. SALL4 was a useful differential marker for combined hepatocellular and cholangiocarcinoma and hepatoid gastric carcinoma. The histogenesis of hepatoid gastric carcinoma expressing SALL4 seems to reflect fetal gut differentiation or involve the germ cell lineage and may be different from that of combined hepatocellular and cholangiocarcinoma involving the hepatic stem cell or progenitor cell lineages. In conclusion, hepatoid gastric carcinoma and combined hepatocellular and cholangiocarcinoma shared morphologies, whereas the distinction of hepatoid gastric carcinoma from combined hepatocellular and cholangiocarcinoma is possible by immunostaining for SALL4. These 2 tumors seem to differ in their histogenesis with respect to SALL4 expression.1.
Human pathology 04/2012; 43(11):1955-63. · 3.03 Impact Factor
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ABSTRACT: Aim: To analyze the clinical features of locally progressed hepatocellular carcinoma (HCC) supplied by portal blood (PB) after transcatheter arterial chemoembolization (TACE). Methods: This cohort included 12 tumors (mean diameter ± SD, 1.8 ± 0.8 cm) in 10 patients. PB supply to tumors was judged by CT during arterial portography (CTAP). Imaging data and the clinical course were retrospectively evaluated. Results: Six tumors initially had a small tumor portion supplied by PB. In four tumors, TACE was incomplete because of technical problems. PB supply to recurrent tumors was demonstrated 7.3 ± 3.7 months after TACE. On follow-up arteriography, all embolized branches were occluded or severely attenuated. Four tumors showing a partial stain were treated by additional TACE (n = 3) or TACE plus radiofrequency (RF) ablation (n = 1), one without staining was treated by RF ablation, and seven were followed-up. All tumors progressed except for one treated by RF ablation. On serial CTAP images, relatively large-diameter portal veins directly entered 11 tumors (91.7%) and connected with intratumoral vessels in nine (75%). During follow-up, partial arterial supply was demonstrated in two tumors and additional TACE was performed. Nine patients died after 31.4 ± 16.2 months due to tumor progression (n = 8), or hepatic failure (n = 1). One patient has survived for 53 months despite multiple tumors. Conclusions: PB supply to locally progressed tumor after TACE became apparent on CTAP. Arterial damage by TACE, incomplete TACE, and preexisting tumor tissues supplied by PB may be the main causes.
Hepatology Research 06/2011; 41(9):853-66. · 2.20 Impact Factor
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ABSTRACT: A 62-year-old Japanese man presented with a 1-month history of inter-digestive epigastralgia. His family history included a sister with gastric cancer. Gastroendoscopy and gastrography demonstrated a type-2 tumor in the upper region of the stomach. CT scan and fluorodeoxyglucose-positron emission tomography (FDG-PET) scan demonstrated gastric cancer and its metastatic lymph nodes. The patient underwent total gastrectomy with splenectomy and extended lymph node dissection. Although postoperative adjuvant chemotherapy by S-1 was started, the deteriorating condition of the patient prevented drug administration and even eating meals. On the 19th postoperative day (POD), FDG-PET scan of the body demonstrated new uptake in the liver and lymph node around the aorta. Without any sign of infection, leukocytosis developed around the 30th POD. On the 49th POD, remarkable uptake in the whole upper abdomen was detected on FDG-PET scan. Finally, leukocyte count increased to 125,200 and granulocyte colony stimulating factor (G-CSF) was elevated to 28 pg/ml on the 54th POD. The patient died of multiple liver metastases and carcinomatous peritonitis only 56 days after surgery. G-CSF-producing tumor is a rare but aggressive disease, particularly as recurrent tumor. If leukocytosis is detected in relation to a non-lympho hematopoietic malignant tumor, G-CSF-producing tumor should be considered and FDG-PET scan is recommended for early detection. Chemotherapy for G-CSF-producing tumor must be conducted as soon as possible.
International Journal of Clinical Oncology 02/2010; 15(2):191-5. · 1.41 Impact Factor
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Shiro Miyayama,
Takeshi Mitsui,
Yoh Zen, Yoshiko Sudo,
Masashi Yamashiro,
Miho Okuda,
Yuichi Yoshie,
Taku Sanada,
Kazuo Notsumata,
Nobuyoshi Tanaka,
Osamu Matsui
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ABSTRACT: Aim: To evaluate the histopathologic findings in the surgical specimen of hepatocelluar carcinoma after transcatheter arterial chemoembolization (TACE) at the most distal portion of the sub-subsegmental artery of the liver (ultraselective TACE). Methods: Histolopathologic findings from nine tumors with a mean diameter of 3.1 cm +/- 1.7 from patients who underwent hepatectomy after ultraselective TACE were evaluated, especially with regard to the relationship between peritumoral liver parenchymal necrosis and portal vein visualization during TACE. Portal vein visualization was classified into three grades by a spot digital radiograph obtained just after TACE: 0, no obvious portal vein visualization; 1, visualization of the portal vein adjacent to the tumor; and 2, visualization in the whole embolized area or extending into the surrounding non-embolized areas. Unenhanced computed tomography (CT) was obtained 1 week later and surgical resection was performed 37 +/- 6.3 days after ultraselective TACE. Results: Portal vein visualization during TACE was classed as grade 1 in 5 tumors and grade 2 in 4. Histopathologically, complete tumor necrosis was observed in 7 tumors (77.8%). In 2 tumors (1 of grade 1, the other grade 2), a small viable portion or viable daughter nodule was seen. Macroscopic parenchymal necrosis adjacent to the tumor was observed in all 4 grade 2 tumors including gas-containing areas on CT obtained 1 week after TACE. Conclusions: 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.
Hepatology Research 12/2008; 39(4):374-81. · 2.20 Impact Factor
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Hideki Niwa,
Motoko Sasaki,
Joji Haratake,
Takahiko Kasai,
Kazuyoshi Katayanagi,
Hiroshi Kurumaya,
Shinji Masuda,
Hiroshi Minato,
You Zen,
Akio Uchiyama,
Atsuo Miwa,
Katsuhiko Saito, Yoshiko Sudo,
Yasuni Nakanuma
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ABSTRACT: Aim: Serum antinuclear antibodies (ANA) are occasionally noted in patients with non-alcoholic steatohepatitis (NASH). We examined the significance of ANA in NASH. Methods: We compared clinicopathological features in 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. Results: ANA-positive NASH was significantly associated with female gender (P = 0.005), high degree of portal inflammation (P = 0.039), interface activity (P = 0.036) and hepatocellular ballooning (P = 0.0008). In addition, ANA of high titer (320-fold or more) was significantly associated with the histological grade and stage of NASH (P = 0.02). The degree of steatosis wais rather mild in the high-titer ANA group(P = 0.01). The analysis of inflammatory cell profiles revealed that CD3-positive T cells were predominant and plasma cells were rather few in the 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. Conclusion: These findings suggest that the presence of ANA may be related to the progression of NASH and that a different type of autoimmune mechanism may be involved in the pathogenesis of NASH with ANA, compared to the pathogenesis of autoimmune hepatitis.
Hepatology Research 12/2007; 37(11):923-31. · 2.20 Impact Factor
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ABSTRACT: We report a rare case of primary small cell carcinoma of the breast. A 44-year-old woman was admitted to our hospital with a mass in her left breast. Fine-needle biopsy revealed small cell carcinoma with neuroendocrine differentiation resembling small cell carcinoma of the lung. Systemic computed tomography (CT) and magnetic resonance imaging (MRI) revealed no primary site in the lung or any other organ. A modified radical mastectomy with removal of the axillary lymph node (Bt + Ax, R2) was performed. Histological examination revealed that the tumor was composed of small round to oval cells with a large nuclear-cytoplasmic ratio. The tumor cells were positive for neuroendocrine differentiation markers such as synaptophysin, CD56, and neuron-specific enolase (NSE), but negative for thyroid transcription factor-1 (TTF-1), leukocyte common antigen (LCA), estrogen receptor (ER), and progesterone receptor (PR). Interestingly, the tumor cells lacked immunoreactivity for epithelial markers, including cytokeratin AE1/3, CAM5.2, and epithelial membrane antigen (EMA). The patient was given adjuvant chemotherapy for axillary lymph node metastasis. There were no signs of recurrence 22 months after surgery.
Breast Cancer 02/2007; 14(4):414-9. · 1.36 Impact Factor
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ABSTRACT: A 42-year-old woman complained of progressive induration in the right palm. As the mass was impossible to separate from the ulnar nerve, we excised the mass together with the digital nerve and grafted 4cm of the sural nerve. The final diagnosis was nodular fasciitis.
Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 02/2005; 39(4):249-51. · 0.94 Impact Factor
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ABSTRACT: Recently, it was shown that osteopontin (OPN) is involved as a chemoattractant cytokine in the recruitment of macrophages and T lymphocytes in the granulomas of diverse etiologies and also plays an important role in the production of autoantibodies and development of autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by immune-mediated bile duct damage with frequent epithelioid granulomas. In this study, the expression of OPN was immunohistochemically examined in 25 PBC and 52 control livers. Epithelioid cells within granuloma in PBC expressed OPN variably. These cells were also positive for CD68, suggesting their histiocyte/macrophage lineage. In addition, strong expression of OPN was seen in the cytoplasm of mononuclear cells infiltrating around granulomas and also damaged bile ducts in PBC. The number of such positive mononuclear cells and the ratio of OPN-positive cells/total infiltrating cells in portal tracts were higher in PBC than in controls. The majority of these OPN-positive cells were found to be IgG- or IgM-producing plasma cells. These suggest that in PBC, OPN is an important immune molecule in portal tracts, and contributes to the recruitment of mononuclear cells into epithelioid granuloma and also participates in bile duct injury via B-cell differentiation and plasma cell expansion.
Pathology International 02/2003; 53(1):8-17. · 1.62 Impact Factor
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ABSTRACT: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are representative autoimmune liver diseases in which hepatocytes and intrahepatic bile ducts, respectively, are selectively damaged by autoimmune mechanisms. Bile duct injury and loss is characteristic of PBC and chronic non-suppurative destructive cholangitis (CNSDC), in particular, is a histological hallmark of PBC. In this report, we present an unusual case of AIH accompanied by CNSDC-like bile duct injury in a 46-year-old woman. The patient's serum aminotransferase level was abnormally high. The serum levels of alkaline phosphatase, gamma-GTP and IgG were also elevated, but the IgM level was within normal limits. The titer of antismooth muscle antibody (SMA) was 1:80, while antinuclear autoantibody (ANA) and the M2 fraction of antimitochondrial antibody (AMA) were both negative. Liver biopsy disclosed CNSDC-like bile duct injuries and severe interface hepatitis and lobular hepatitis with perivenular zonal necrosis were observed. The aggregate score of the International Autoimmune Hepatitis Group corresponded to the category of probable AIH. Immunohistochemically, histocompatibility leukocyte antigen-DR, which is aberrantly expressed in the damaged bile ducts of PBC, was not found in the injured bile ducts of this case. Laboratory data were much improved by treatment with prednisone, but ursodeoxycholic acid was not effective. Although the possibility of an overlapping syndrome of AIH- and AMA-negative PBC could not be excluded, this case was diagnosed as AIH with CNSDC-like bile duct lesions.
Pathology International 08/2002; 52(7):478-82. · 1.62 Impact Factor
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ABSTRACT: The characteristic serological feature of primary biliary cirrhosis (PBC) is the presence of antimitochondrial antibodies (AMAs), and the major proteins recognized by AMAs are subunits of the 2-oxo acid dehydrogenase complexes (2-OADC), including the E2 components of the pyruvate dehydrogenase complex (PDC), the 2-oxo-glutarate dehydrogenase complex (OGDC), the branched-chain 2-oxoacid dehydrogenase complex (BCOADC), the E3 binding protein (E3BP or protein X) and the E1a component of mammalian PDC. Previous work has postulated that either E3BP, or a molecule cross-reactive with the PDC-E2 molecule, is uniquely expressed on the surface of biliary epithelial cells in PBC. To address this issue, we performed in situ hybridization for all of the major 2-OADC components at the mRNA level, including PDC-E2, BCOADC-E2, OGDC-E2, PDC-E1a, BCOADC-E1a, OGDC-E1, and E3BP using 13 PBC and 9 control livers using 7 mitochondrial antisense probes. In both PBC and controls, the expression of all 2-OADC component mRNA studied herein were found in hepatocytes and infiltrating mononuclear cells, without significant differences. Interestingly, however, despite published data on immunohistochemical staining, interlobular bile ducts including the injured bile ducts in PBC were generally negative or only faintly positive, with the exception of 1 bile duct in 1 of 13 cases of PBC and 1 of 9 control liver specimens. Moreover, confocal microscopic examination and image analysis revealed that the mRNA signal intensity of each of the 2-OADC components in the bile ducts of PBC was relatively lower in comparison with control liver diseases. These data suggest that continuous enhanced synthesis of the 2-OADC components is not likely to be occurring in the biliary epithelial cells in PBC, and that an increase of PDC-E2 or E3BP immunoreactivity in PBC is caused by exogenous imported or cross-reactive molecules
Hepatology 06/1999; 30(1):36 - 45. · 11.66 Impact Factor
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ABSTRACT: Background/Aims: In primary biliary cirrhosis (PBC), the intrahepatic small bile ducts are selectively damaged by immune attacks, followed by progressive loss mainly due to apoptosis. Compared to the intercellular signaling such as the CD95/CD95 ligand interaction, little is known about alterations in intracellular cell cycle regulatory proteins and genotoxic damage in this apoptotic process. WAF1 is a potent and reversible inhibitor of cell cycle progression at both the G1 and G2 checkpoint and upregulated WAF1 induces irreversible G1 arrest and apoptosis. Transcriptional activation of the WAF1 gene is induced by the upregulated p53 in response to DNA damage. In this study, the cell cycle regulatory process of apoptosis in PBC was examined with respect to expression of WAF1.Methods: Immunostaining for WAF1 and p53 was performed using 11 liver sections of PBC and 26 control livers. In addition, Ki67, apoptosis (TUNEL-positive), and human telomerase RNA (hTR) were also detected.Results: WAF1 was expressed in the nuclei of several epithelial cells in most damaged bile ducts in PBC but infrequently or rarely in controls. Some of these cells were also positive for p53, while the remainder were not. Ki67 immunostaining and TUNEL disclosed that the bile ducts in PBC showed increased cell division as well as enhanced apoptosis. Immunostaining of Ki67 and TUNEL staining showed that WAF1-positive cells were not proliferating, while some WAF1-positive cells were undergoing apoptosis. Moreover, the bile ducts lacked hTR expression, implying progressive shortening of telomeres during increased cell divisions.Conclusions: It seems possible that in PBC, expression of WAF1 on biliary epithelial cells relates to the apoptosis. p53 may be involved in this upregulation. This may be due to physiological upregulation of WAF1 and p53 in response to genotoxic damage such as oxidative stress associated with cholangitis, suggesting other processes than CD95/CD95 ligand interaction in biliary epithelial apoptosis in PBC.
Journal of Hepatology.
