Lobar decrease in 99mTc-GSA accumulation in hilar cholangiocarcinoma.
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Hilar cholangiocarcinoma can obstruct hepatic ducts and involve the portal veins. Both biliary stasis and decrease in portal venous flow are known to reduce 99mTc-diethylenetriamine pentaacetic acid-galactosyl human serum albumin (GSA) accumulation. The specific relationship between these pathological conditions due to hilar cholangiocarcinomas and 99mTc-GSA accumulation has never been clarified. METHODS: Sixteen patients with hilar cholangiocarcinomas who underwent 99mTc-GSA liver scintigraphy were reviewed. The relationship between significant decrease in 99mTc-GSA accumulation and lobar biliary stasis, or decrease in the portal venous flow, was evaluated. Average counts of region of interest placed in both right and left lobes were compared in the same transaxial SPECT section. Count ratios of right and left lobes were calculated. RESULTS: Significant lobar decrease in 99mTc-GSA accumulation was observed in 6 of the 16 patients. Ipsilateral portal venous stenosis or obstruction was seen in all these 6 patients, whereas ipsilateral portal venous stenosis or obstruction was seen in only 1 of the other 10 patients. Symmetric bile duct dilatation was seen in 13 patients, and asymmetric bile duct dilatation was seen in 3. Lobar decrease in 99mTc-GSA accumulation correlated well with decrease in ipsilateral portal venous flow (P < 0.0005). The count ratio was significantly reduced when unilateral portal venous flow decreased (P < 0.05). CONCLUSION: Using 99mTc-GSA liver scintigraphy, we can predict lobar decrease in ipsilateral portal venous flow and monitor hepatic functional lateralities in patients with hilar cholangiocarcinomas. (+info)
ANIT-induced disruption of biliary function in rat hepatocyte couplets.
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alpha-Naphthylisothiocyanate (ANIT) induces intrahepatic cholestasis in rats, involving damage to biliary epithelial cells; our study aims to investigate whether disruption of biliary function in hepatocytes can contribute to early stages of ANIT-induced intrahepatic cholestasis. Isolated rat hepatocyte couplets were used to investigate biliary function in vitro by canalicular vacuolar accumulation (cVA) of a fluorescent bile acid analogue, cholyl-lysyl-fluorescein (CLF), within the canalicular vacuole between the two cells. After a 2-h exposure to ANIT, there was a concentration-dependent inhibition of cVA (cVA-IC50; 25 microM), but no cytotoxicity (LDH leakage or [ATP] decline) within this ANIT concentration range. There was no loss of cellular [GSH] at low ANIT concentrations, but, at 50 microM ANIT, a small but significant loss of [GSH] had occurred. Diethylmaleate (DEM) partially depleted cellular [GSH], but addition of 10 microM ANIT had no further effect on GSH depletion. Reduction in cVA was seen in DEM-treated cells; addition of ANIT to these cells reduced cVA further, but the magnitude of this further reduction was no greater than that caused by ANIT alone, indicating that glutathione depletion does not enhance the effect of ANIT. F-actin distribution (by phalloidin-FITC staining) showed an increased frequency of morphological change in the canalicular vacuoles but only a small, non-significant (0.05 < p < 0.1) increase in proportion of the F-actin in the region of the pericanalicular web. The results are in accord with a disruption of hepatocyte canalicular secretion within two h in vitro, at low, non-cytotoxic concentrations of ANIT, and the possible involvement of a thiocabamoyl-GSH conjugate of ANIT (GS-ANIT) in this effect. (+info)
Lymph node metastasis in intrahepatic cholangiocarcinoma.
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BACKGROUND: Lymph node metastasis is a significant prognostic factor in intrahepatic cholangiocarcinoma. This study was aimed at investigating lymph node metastasis in intrahepatic cholangiocarcinoma and to examine whether the extent of metastasis affects outcomes after surgery. METHODS: From 1980 through 1996, 70 patients with intrahepatic cholangiocarcinoma underwent hepatectomy, with a 50% curative resection rate. Lymph node dissection was performed in 51 patients, and the presence of lymph node metastasis was examined microscopically. The metastatic nodes were divided into groups N1, N2 or N3 using the classification proposed by the Liver Cancer Study Group of Japan. RESULTS: Twenty-three patients had lymph node metastasis. Metastasis was to N1 nodes in 10 patients, to N2 nodes in nine patients and to N3 nodes in four patients. Nineteen patients had metastatic nodes in the hepatoduodenal ligament, which was the most common metastatic site regardless of tumor location. The five-year survival rate in patients with lymph node metastasis (0%) was significantly lower (p < 0.0001) than that in patients without lymph node metastasis (51 %); however, five-year survival rates did not differ between patients with metastases to N1, N2 and N3 nodes. CONCLUSIONS: Lymph nodes in the hepatoduodenal ligament may be sentinel nodes for intrahepatic cholangiocarcinoma, and outcomes after surgery for patients with lymph node metastasis are poor regardless of the sites of nodal metastasis. (+info)
Promoting effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone on rat glandular stomach carcinogenesis initiated with N-methyl-N'-nitro-N-nitrosoguanidine.
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The modifying effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated water, on the development of glandular stomach cancers were investigated in Wistar rats. A total of 120 males, 6 weeks of age, were divided into six groups. After initiation with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) solution and 5% NaCl diet for 8 weeks, 30 rats each in groups 1-3 were given MX in the drinking water at concentrations of 30, 10, or 0 ppm for the following 57 weeks. Ten animals each in groups 4-6 were administered the MX without prior carcinogen exposure. There were no statistical significant differences in final body weights between the groups. The incidences and multiplicities of adenocarcinomas in the glandular stomachs were significantly higher (P < 0.05) in the initiated 30 ppm MX group than those in the MNNG/NaCl group. The incidences of atypical hyperplasias in the glandular stomachs were also significantly increased (P < 0.05 or 0.01) by the MX treatments. With their multiplicity, the effects were clearly dose dependent. Interestingly, the 30 ppm MX alone itself induced atypical hyperplasias in the pylorus, although the incidences and severity were low. Moreover, MX showed a tendency to enhance the development of intrahepatic cholangiocellular tumors and thyroid follicular cell tumors in the MNNG-treated animals. The results of the present study thus indicate that MX exerts promoting effects when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats. (+info)
Acute carbon tetrachloride feeding induces damage of large but not small cholangiocytes from BDL rat liver.
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Bile duct damage and/or loss is limited to a range of duct sizes in cholangiopathies. We tested the hypothesis that CCl4 damages only large ducts. CCl4 or mineral oil was given to bile duct-ligated (BDL) rats, and 1, 2, and 7 days later small and large cholangiocytes were purified and evaluated for apoptosis, proliferation, and secretion. In situ, we measured apoptosis by morphometric and TUNEL analysis and the number of small and large ducts by morphometry. Two days after CCl4 administration, we found an increased number of small ducts and reduced number of large ducts. In vitro apoptosis was observed only in large cholangiocytes, and this was accompanied by loss of proliferation and secretion in large cholangiocytes and loss of choleretic effect of secretin. Small cholangiocytes de novo express the secretin receptor gene and secretin-induced cAMP response. Consistent with damage of large ducts, we detected cytochrome P-4502E1 (which CCl4 converts to its radicals) only in large cholangiocytes. CCl4 induces selective apoptosis of large ducts associated with loss of large cholangiocyte proliferation and secretion. (+info)
Expression of p73, a novel protein related to the p53 tumour suppressor p53, and apoptosis in cholangiocellular carcinoma of the liver.
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p73, the first homologue of the tumour suppressor protein p53, was recently discovered on chromosome 1p36 and has been shown to induce apoptosis in a p53-like manner. The present study was performed with the aim of investigating the expression of p53, its new homologue p73 and the occurrence of apoptosis in cholangiocellular carcinoma. Protein levels of p73 were examined in 41 patients with curatively (R0-) resected cholangiocellular carcinomas with an antiserum, raised against a peptide in the N-terminal domain of p73. The incidence of mutations in the p53 gene was analysed by direct sequencing and also immunohistochemically. Apoptotic cell death was assessed using in-situ end-labelling (ISEL) technique in combination with morphological criteria. The results obtained were correlated with patient survival. Immunostaining of p73 protein was detected in 17/41 carcinomas examined (41%). The immunoreactivity was confined to the cell nucleus. In 15/41 patients (37%), mutations of the p53 gene were observed. Eleven out of these 15 patients stained also positive for p73. In contrast, out of 26 patients without any detectable p53 mutation, only six exhibited p73 immunostaining. We failed to observe a correlation between p73 expression or p53 and apoptosis within a given tumour. Survival analysis including the parameters stage and grade of disease, p73 and p53, and also apoptosis, showed that tumour stage and grade as well as p53 and p73 were significantly related to prognosis. In Cox regression survival analysis, however, only extent of primary tumour and lymph node status had an independent prognostic impact. Our results with a high prevalence of p73 within tumours harbouring mutated p53 gene suggest that p73 could compensate for p53 function. We failed to establish p73 or p53 as independent prognostic factors in cholangiocellular carcinoma of the liver. (+info)
Intrahepatic peripheral cholangiocarcinoma: CT features in 18 pathologically proven cases.
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OBJECTIVE: To determine the morphological features of 18 pathologically proven intrahepatic peripheral cholangiocarcinoma (IHPCC) cases in computerized tomography (CT) image. METHODS: All 18 patients had CT, using Picker I.Q.T/C and taking pre-contrast continuous 10-mm sections throughout the liver and post-contrast continuous 10-mm sections throughout the focuses. RESULTS: The disease was characterized in CT image by the following: all focuses were found in the periphery of the liver and shown as a lobulated or fused hypodense space-occupying mass; there were one or more divergent or confluent, circular or irregular cystic areas with much lower density, in the majority. All focuses could be enhanced slightly and most revealed a dim edge. Dilated bile ducts around the focus were found frequently; the dilated bile ducts especially seemed to encircle the focus (33.3%, 6/18). This phenomenon were referred to as "encysted sign of dilated bile ducts". CONCLUSIONS: CT scanning should be one of the most important investigative methods for IHPCC due to the disease characteristics identified in CT image, especially "encysted sign of dilated bile ducts" which possesses specificity in diagnosing the disease. (+info)
Long-lasting sonographic and histopathological findings in cured clonorchiasis of rabbits.
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To ascertain residual sonographic and histopathological findings of clonorchiasis after treatment, the present study evaluated sonographic findings in rabbits which were infected with 500 metacercariae of C. sinensis every 6 months for 18 months after treatment with praziquantel. The sonographic findings were analyzed in terms of intrahepatic bile duct dilatation and periductal echogenicity, and histopathological findings were observed after the last sonographic examination. Compared with the sonographic findings before treatment, dilatation of the intrahepatic bile ducts became mild to some degree in four of the seven cases and increased periductal echogenicity resolved in four of them. The histopathological specimens after 18 months showed that periductal inflammation has almost resolved but moderate dilatation of the intrahepatic ducts and mucosal hyperplasia persisted. The periductal fibrosis minimally resolved. The long-lasting sonographic findings in cured clonorchiasis make sonography less specific. (+info)