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. (1/118)

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)

Immunohistochemical localization of inducible nitric oxide synthase and 3-nitrotyrosine in rat liver tumors induced by N-nitrosodiethylamine. (2/118)

Human liver cancers have been associated mainly with chronic inflammations such as viral hepatitis B or C. This suggests that prolonged cell damage by chronic inflammation is critical in cancer development. Overproduction of nitric oxide (NO.) and its derivative (NOx, peroxynitrite) has been implicated as a cause of tissue damage by inflammation, thus contributing to tumor promotion. We have demonstrated the expression of the inducible isoform of nitric oxide synthase (iNOS) and 3-nitrotyrosine, a marker of peroxynitrite formation, by immunohistochemistry in preneoplastic and neoplastic rat liver tissues induced by continuous infusion of N-nitrosodiethylamine with mini-pumps. The preneoplastic lesions were characterized by proliferation of phenotypically altered hepatic foci (PAHF), dysplastic hepatocytes and oval cells. Histologically, the tumors were hepatocellular carcinomas (HCCs) of trabecular, (pseudo)glandular and solid types with or without cholangiocellular involvement. iNOS was located mainly in oval cells, capillary endothelial and muscular cells, epithelia of cholangiomas and glandular HCCs. 3-Nitrotyrosine was observed in the cytoplasms of PAHF and dysplastic hepatocytes in preneoplasias and in the cytoplasms of some living or apoptotic HCC cells, connective tissues, proteinaceous fluids, sinusoidal endothelia of tumorous hepatocytes and cholangiomas in tumors. From these observations, we suggest that: (i) chronic tissue damage by chemical carcinogens may act to induce iNOS and peroxynitrite formation; (ii) oval cells play a key role in development and/or growth of tumor tissues by producing NO. via iNOS, which may also cause tissue damage by peroxynitrite; (iii) iNOS can be considered as a phenotypic marker in cells of oval cell lineage and neovascularized capillaries in tumor tissues.  (+info)

Primary liver carcinoma in genetic hemochromatosis reveals a broad histologic spectrum. (3/118)

Hepatocellular carcinoma (HCC) is a well-known complication of genetic hemochromatosis (GH). However, the frequency of primary liver carcinoma (PLC) with biliary differentiation, such as cholangiocarcinoma (CC) and combined hepatocholangiocarcinoma (CHCC), in GH remains unclear We analyzed the histologic type of 20 PLCs occurring in the background of GH; all patients were homozygotic for the C282Y mutation. Ten were depleted of iron by successive phlebotomies, while the remaining 10 were untreated. Histologically, 13 cases were classified as HCC, 3 as CC, and 4 as CHCC. Immunohistochemical detection of Hep Par 1, cytokeratin 19 (CK19), and MUC1 supported this classification; PLC with biliary differentiation was immunoreactive for MUC1 in 86% (6/7) of cases and for CK19 in 100% (7/7) of cases. The nontumoral liver exhibited no cirrhosis or extensive fibrosis in 6 cases. Von Meyenburg complexes were present in 11 cases and intraparenchymal bile duct adenomas in 3. These data suggest that PLCs in patients with GH present a wide histologic spectrum, with tumors showing frequent biliary differentiation; may arise on a nonfibrotic or a cirrhotic liver; and often are associated with Von Meyenburg complexes and to a lesser extent with bile duct adenomas.  (+info)

Management strategies in resection for hilar cholangiocarcinoma. (4/118)

Between 1960 and 1990, resection was performed in 23 of 122 patients who underwent surgical treatment for hilar cholangiocarcinoma. Local excision of the lesion alone was performed in 10 cases (43%). Hepatic resection for tumor extending to the secondary bile ducts or hepatic parenchyma was performed in 13 cases (57%): extended right hepatectomy (3), right hepatectomy (1), extended left hepatectomy (6), left hepatectomy (2), and left lobectectomy (1). In three other cases, resection by total hepatectomy and liver transplantation was performed, but these were not included in the analysis of results for resection. Significant operative complications occurred in only two cases (8.7%), and the operative mortality rate was zero. In four cases, complete excision of the tumor could not be achieved macroscopically (macroscopic curative resection rate 19/122; 15.6%). In nine cases, the margins of the resected specimens were free from tumor on histologic examination (microscopic curative resection rate, 9/122; 7.4%). In 10 cases, the resection margins were found to contain tumor on histologic examination. The overall survival rate was 87% at 1 year, 63% at 2 years, and 25% at 3 years (median survival, 24 months). The survival and freedom from recurrence rates for patients with free resection margins was superior to that for patients with involved resection margins or residual macroscopic disease. A potentially curative resection, with histologically negative margins and no recurrence to date, was achieved in seven patients using the following procedures: local excision for two type I lesions; left hepatectomy plus excision of segment 1 for two type IIIb lesions and one type IV lesion; right hepatectomy and right hepatectomy plus excision of segment 1 for two type IIIa lesions. These results indicate that improved survival in hilar cholangiocarcinoma can be achieved by resection, with minimal morbidity and zero mortality rates, if histologically free resection margins are obtained. To achieve this, we recommend the following procedures for each type of lesion, based on our experience and on anatomic considerations: local excision for type I; local excision plus resection of segment 1 for type II; local excision, resection of segment 1, and right or left hepatectomy for types IIIa and b; hepatectomy plus liver transplantation for type IV.  (+info)

Low frequency of p53 gene mutation in tumors induced by aflatoxin B1 in nonhuman primates. (5/118)

Aflatoxin B1 has been suggested as a causative agent for a G to T mutation at codon 249 in the p53 gene in human hepatocellular carcinomas from southern Africa and Qidong in China. To test this hypothesis, nine tumors induced by aflatoxin B1 in nonhuman primates were analyzed for mutations in the p53 gene. These included four hepatocellular carcinomas, two cholangiocarcinomas, a spindle cell carcinoma of the bile duct, a hemangioendothelial sarcoma of the liver, and an osteogenic sarcoma of the tibia. None of the tumors showed changes at the third position of codon 249 by cleavage analysis of the HaeIII enzyme site at codon 249. A point mutation was identified in one hepatocellular carcinoma at the second position of codon 175 (G to T transversion) by sequencing analysis of the four conserved domains (II to V) in the p53 gene. These data suggest that mutations in the p53 gene are not necessary in aflatoxin B1 induced hepatocarcinogenesis in nonhuman primates. The occurrence of mutation in codon 249 of the p53 gene in selective samples of human hepatocellular cancers may indicate involvement of environmental carcinogens other than aflatoxin B1 or that hepatitis B virus-related hepatitis is a prerequisite for aflatoxin B1 induction of G to T transversion in codon 249.  (+info)

Evaluation of liver tumors using fluorine-18-fluorodeoxyglucose PET: characterization of tumor and assessment of effect of treatment. (6/118)

To evaluate glucose metabolism in patients with tumors involving the liver, 35 patients with liver lesions had PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG). FDG (148 MBq) was injected and radioactivity of the tumor was scanned dynamically by PET. The rate constants (k1, k2, k3, k4) of FDG in a metabolic model were calculated. The results were compared to hexokinase activity in the excised tumor specimens. k3 was found to reflect tumor hexokinase activity. When k3 was used as an index (cut-off value: 0.025), it was possible to distinguish benign and malignant tumors. k4 was significantly higher in hepatocellular carcinoma. By using k3 and k4 as indices, one could assess the degree of differentiation of hepatocellular carcinoma. After treatment, k3 decreased according to the effectiveness of therapy and thus may be a useful index for quantitatively assessing tumor viability.  (+info)

Analysis of failure after curative irradiation of extrahepatic bile duct carcinoma. (7/118)

Thirty-four patients with subtotally resected or unresectable carcinoma of the extrahepatic bile ducts received radiation therapy; a minimum of 45 Gy (external beam) to the tumor and regional lymph nodes +/- 5-fluorouracil (5-FU). Seventeen patients received an external beam boost of 5 to 15 Gy to the tumor, and a specialized boost was used in the remaining 17 patients (iridium-192 transcatheter seeds in 10 and intraoperative radiation therapy [IORT] with electrons in seven). The median time to death in all 34 patients was 12 months (range, 4 to 98-months). The only patients who survived longer than 18 months were those either with gross total or subtotal resection before external irradiation (2 of 6) or who received specialized boosts (192Ir, 3 of 10; IORT, 3 of 7). Local failure was documented in 9 of 17 patients who received external beam irradiation alone +/- 5-FU, 3 of 10 patients who received an 192Ir boost, and 2 of 6 patients who received an IORT boost with curative intent.  (+info)

Clinical evaluation of a new serum tumour marker CA 242 in pancreatic carcinoma. (8/118)

The aim of this study was to evaluate the new monoclonal tumour marker CA 242 in the diagnosis of pancreatic carcinoma and to compare it with the established markers CA 50 and CEA. Serum concentrations were determined in 113 patients with jaundice, in 20 patients with laboratory values suggesting cholestasis, and in 60 patients with a suspicion to have chronic pancreatitis. Twenty-four of these 193 patients had pancreatic carcinoma and two patients had carcinoma of papilla of Vater. The sensitivities of CA 242, CA 50 and CEA were 80.7%, 96.1%, and 92.3%, respectively. The specificities were 79.0%, 58.0%, and 59.2%. The sensitivities of combinations of CA 50 and CEA with CA 242 did not exceed the sensitivity of CA 50 alone. The specificity of CA 242 was improved by combining it with CEA (92.2%). The serum marker CA 242 seems to be less sensitive than CEA and CA 50 in the detection of pancreatic carcinoma, but it may prove useful because of its high specificity.  (+info)