Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis

Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis,except epidemic schistosomiasis.Among them,primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues,giving rise to systemic amyloidosis,due to a progressive and unresolved inflammatory process,and its possible association with inflammatory bowel diseases.Nevertheless,only one such case has been reported in the literature to date.We report a 69-year-old Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis,without any evidence of other inflammatory disorders.As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4,the presence of IgG4 + plasma cells was examined systemically,resulting in unexpected documentation of Congo-red-positive amyloid deposits,but not IgG4 + plasma cells,in the liver,stomach and salivary glands.Elevated serum IgG4 is the hallmark of IgG4-related disease,including IgG4-associated cholangitis,but it has also been demonstrated in certain patients with PSC.Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.

Expression of pituitary tumor transforming gene in human gastric carcinoma

AIM:Pituitary tumor transforming gene (PTTG1) is overexpressed in a variety of tumors, including carcinomas of the lung, breast, colon, as well as in leukemia, lymphoma and pituitary adenomas.However,there is little information on its expression in gastric carcinoma. We sought to investigate the expression of PTTG1 in gastric carcinoma and to explore the relationship between its expression and clinicopathological factors.METHODS:We studied 75 primary human gastric adenocarcinomas, including 17 mucosal carcinomas, 21 submucosal infiltrative carcinomas, 12 carcinomas invading proprial muscle layers, 6 carcinomas reaching the subserosa,and 19 carcinomas penetrating the serosal surface.Immunohistochemical analysis was performed using paraffinembedded sections of gastric adenocarcinomas.RESULTS: PTTG1 was expressed heterogeneously in carcinomas. Positive PTTG1 staining was observed in 65.3% of the carcinomas (49 of 75). Its expression did not correlate significantly with either the histological type or the depth of infiltration of the gastric carcinomas.However,a statistical analysis showed significant differences between the primary adenocarcinomas and the associated metastatic lymph nodes.CONCLUSION: The results of this study demonstrate that PTTG1 expression is enhanced in metastatic lymph nodes in comparison to that in primary carcinomas. We suggest that PTTG1 may contribute to lymph node metastases in gastric carcinoma.

A novel animal model for in vivo study of liver cancer metastasis

AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-man gastric cancer cells(h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator(uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient(SCID) mouse line(uPA/SCID mice).Host mice were divided into two groups(A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index(RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A(RI = 22.0% ± 2.6%).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL(range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies(RI = 12.0% ± 6.8% and 66.0% ± 12.3%,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line.This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis.

Expression of β-catenin in hepatocellular carcinoma

AIM: The β-catenin has been recognized as a critical member of the Wnt signaling pathway and plays an important role in the generation/differentiation of many tissues. Inappropriate activation of this pathway has been implicated in carcinogenesis. The mechanism underlying the development as well as its prognosis of hepatocellular carcinoma (HCC) has remained unclear. The purpose of this study is to analyze the expression of β-catenin in HCC in relation to histological grades and viral hepatitis backgrounds.METHODS: Thirty-two sections were selected at random from autopsy and surgical cases of HCC. Immuohistologically,the location and positivity of β-catenin expression in HCC was examined.RESULTS: Normal hepatocytes did not express β-catenin.In 78% of HCC β-catenin was expressed at the membrane of the cells, with or without cytoplasmic and/or nuclear expression. The tumor cells with well- and moderatelydifferentiated grades expressed frequently at the membrane and cytoplasm compared with poorly-differentiated type.Nuclear expression of β-catenin was prone to occur in the tumor cells of poorly-differentiated grade. There were 15% of hepatitis C virus (HCV) backgrounds with nuclear expression. In contrast, there was 38% with nuclear expression in hepatitis B virus (HBV) backgrounds. In nonBnonC hepatitis, no case expressed nuclear β-catenin.CONCLUSION: The β-catenin expression in HCC cells was heterogenous among types of hepatitis viral infection.Wnt signaling pathway might be deeply involved in less-differentiated HCC and HBV background.

Fenofibrate-induced liver injury

TO THE EDITOR Fenofibrate is a member of such fibrate class agents as bezafibrate and it work as a ligand of PPARα, and also shows a potent triglyceride-lowering effect. The elevation of aminotransferase levels has been frequently observed after the administration of fenofibrate and this phenomenon is considered to be non-pathological because fenofibrate activates the gene expression of the aminotransferases. Recently, fenofibrate has been used not only for hypercholesterolemia but also for primary biliary cirrhosis (PBC)[1,2]. However, the occurrence of liver injury induced by fenofibrate has not yet been reported written in the English literature. We herein report a rare case of liver injury due to the oral use of this drug.

mPGES-1 expression in non-cancerous liver tissue impacts on postoperative recurrence of HCC

AIM:To investigate whether microsomal prostaglandin E synthase-1 (mPGES-1) expression in hepatocellular carcinoma (HCC) and in non-cancerous liver affects HCC prognosis after hepatectomy. METHODS: The relationship between patient clinical prof iles, tumor factors, surgical determinants, and mPGES-1 expression and the recurrence-free survival rate were examined in 64 patients who underwent curative hepatectomy between March 2003 and December 2006. RESULTS: The scores for mPGES-1 expression were higher in well differentiated and moderately differentiated HCC tissues than in poorly differentiated HCC tissues (well differentiated, 5.1 ± 2.7; moderately differentiated, 5.1 ± 1.7; poorly differentiated, 3.0 ± 1.8). In noncancerous liver tissues, the mPGES-1 levels were higher in injured liver tissues than in normal tissues. Cirrhotic livers had higher mPGES-1 levels than livers with chronic hepatitis (normal livers, 3.3 ± 0.7; chronic hepatitic livers, 5.4 ± 1.9; cirrhotic livers, 6.4 ± 1.6). A univariate analysis revealed that the recurrence-free survival rate was signif icantly lower in patients with vascular invasion,a higher mPGES-1 level in non-cancerous liver tissue,a larger tumor diameter (≥5 cm), and a lower serum albumin level (≤3.7 g/dL). The mPGES-1 expression in HCC tissues did not correlate well with postoperative recurrence. A multivariate analysis demonstrated that the presence of vascular invasion and higher mPGES-1 levels were statistically significant independent predictors for early postoperative recurrence of HCC.CONCLUSION: Increased mPGES-1 expression in noncancerous liver tissues is closely associated with the early recurrence of HCC after curative resection.

Endoscopic identification of Peyer's patches of the terminal ileum in a patient with Crohn's disease

We presented a 20-year-old patient with Crohn's disease (CD). Colonoscopy revealed longitudinal ulceratlon in the terminal ileum and rectal aphtoid ulcers, After treatment with mesalamine and total parenteral nutrition, repeat colonoscopy revealed a granular elevated area in the terminal ileum, which appeared as an irregular dome-like elevation with irregularly arranged vill on magnifying endoscopy. Biopsy specimens taken from the region showed microgranulomas and lymphoid hyperplasia, Scanning electron microscopy revealed the presence of M cells, conthming that the area corresponded to Peyer's patches. Peyer's patches by magnifying endoscopy and electron microscopy may provide insights into the pathogenesis oF CD.