K-ras mutations in the bile of patients with primary sclerosing cholangitis.
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BACKGROUND AND AIMS: The development of cholangiocarcinoma (CCC) is a complication of primary sclerosing cholangitis (PSC). To date, no reliable factors have been described which can define those PSC patients at high risk for the development of CCC and the clinical diagnosis of CCC in PSC patients is difficult. Therefore, molecular markers of cholangiocarcinogenesis, such as K-ras mutations, may improve the early diagnosis of CCC or the timing of liver transplantation. METHODS: K-ras mutations were analysed by enriched polymerase chain reaction/restriction fragment length polymorphism in the bile fluid of 56 PSC patients and 20 patients with other cholestatic diseases. To assess the value of K-ras mutations as a risk factor for cholangiocarcinogenesis, patients were prospectively investigated over a mean period of 31.5 months. RESULTS: In contrast with the control group, 17 (30%) patients with PSC revealed K-ras mutations in bile fluid. The mean Mayo score was not significantly different between PSC patients with (mean score 0.70) and without (mean score 0.13; p=0.2) K-ras mutations. In contrast with the group of PSC patients without K-ras mutations, four CCCs and two dysplasia were diagnosed in the group of patients with K-ras mutations during the follow up investigation (p<0.001). CONCLUSIONS: Our results indicate that K-ras mutations in bile fluid of PSC patients represent frequent early events during cholangiocarcinogenesis. However, most of the PSC patients with K-ras mutations remained tumour free after a long follow up investigation which is in agreement with the fact that these mutations are not specific for malignancy but may also occur in normal bile duct mucosa or in dysplasias. Therefore, analysis of K-ras mutations in bile should not be used for diagnosis of CCC in PSC patients. However, the results of our prospective follow up investigation indicate that K-ras mutations in bile fluid of PSC patients have to be considered as risk factors for the development of CCC which may have implications for the timing of liver transplantation. (+info)
Lymph node metastasis from hilar cholangiocarcinoma: audit of 110 patients who underwent regional and paraaortic node dissection.
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OBJECTIVE: To assess the status of the regional and paraaortic lymph nodes in hilar cholangiocarcinoma and to clarify the efficacy of systematic extended lymphadenectomy. SUMMARY BACKGROUND DATA: There have been no studies in which regional and paraaortic lymphadenectomies for hilar cholangiocarcinoma have been routinely performed. Therefore, the metastasis rates to the regional and paraaortic nodes, the mode of lymphatic spread, and the effect of extended lymph node dissection on survival remain unknown. METHODS: This study involved 110 patients who underwent surgical resection for hilar cholangiocarcinoma with lymph node dissection including both the regional and paraaortic nodes. A total of 2,652 nodes retrieved from the surgical specimens were examined microscopically. RESULTS: Of the 110 patients, 52 (47.3%) had no involved nodes, 39 (35.5%) had regional lymph node metastases, and 19 (17.3%) had regional and paraaortic node metastases. The incidence of positive nodes was significantly higher in the patients with pT3 disease than in those with pT2 disease. The pericholedochal nodes were most commonly involved (42.7%), followed by the periportal nodes (30.9%), the common hepatic nodes (27.3%), and the posterior pancreaticoduodenal nodes (14.5%). The celiac and superior mesenteric nodes were rarely involved. The 3-year and 5-year survival rates were 55.4% and 30.5% for the 52 patients without involved nodes, 31.8% and 14.7% for the 39 patients with regional node metastases, and 12.3% and 12.3% for the 19 patients with paraaortic node metastases, respectively. Of the 19 patients with positive paraaortic nodes, 7 had no macroscopic evidence of paraaortic disease on intraoperative inspection. The survival in this group was significantly better than in the remaining 12 patients. CONCLUSION: The paraaortic nodes and the regional nodes are frequently involved in advanced hilar cholangiocarcinoma. Whether extended lymph node dissection provides a survival benefit requires further study. However, the fact that long-term survival is possible despite pN2 or pM1 disease encourages the authors to perform an aggressive surgical procedure with extended lymph node dissection in selected patients with hilar cholangiocarcinoma. (+info)
Detection of hepatitis C virus RNA sequences in hepatic portal cholangiocarcinoma tissue by reverse transcription polymerase chain reaction.
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OBJECTIVE: To detect hepatitis C virus (HCV) RNA sequences in the hepatic portal cholangiocarcinoma tissues and their relationship. METHODS: RNA was extracted from paraffin-embedded cholangiocarcinoma tissues of 6 patients by guanidinium method, subjected to reverse transcription and then amplified by double PCR technique using nested primers from the highly conserved 5' noncoding region of HCV genome. RESULTS: HCV RNA of 5' NT sequences was found in the hepatic portal cholangiocarcinoma tissues of 5 out of 6 (83%) patients. CONCLUSIONS: HCV RNA sequences present with high infectious rate in cholangiocarcinoma, and reverse transcription polymerase chain reaction (RT-PCR) assay using primers derived from 5' NT region of HCV sequence is most useful in detecting HCV infection. The development of cholangiocarcinoma awaits further studies. (+info)
Prevalence and clinical relevance of serum anti-p53 antibodies in patients with cholangiocarcinoma.
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Cholangiocarcinoma (CCA) constitutes carcinoma of the bile duct found at a high prevalence in northeastern Thailand. In the present study, we examined the sera of altogether 82 Thai CCA patients for the presence of anti-p53 antibodies in order to investigate a role of the tumor suppressor gene, p53 in the carcinogenesis. Our results revealed anti-p53 antibodies in 7.3% of the cases tested, which conforms to the prevalence rate of p53 gene mutation recently reported at 5% among Thai patients. With limited number of the patients, anti-p53 antibodies were rapidly detected more frequently among patients with peripheral tumors than those with central tumors. However, further studies is required to establish significance and prognostic value of the antibodies in the context of CCA. (+info)
Genetic alterations and growth pattern in biliary duct carcinomas: loss of heterozygosity at chromosome 5q bears a close relation with polypoid growth.
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Biliary duct carcinomas (BDCs) are relatively rare and the carcinogenic mechanisms underlying their induction are poorly understood. There are two growth patterns, polypoid and non-polypoid infiltrative type, but little information is available concerning the relation between growth pattern and genetic alterations. A comparative study was therefore conducted to clarify if differences in genetic changes, including loss of heterozygosity (LOH) at 5q, 9p, 17p, and 18q, and K-ras mutations exist between polypoid and non-polypoid infiltrative type BDCs. LOH analysis was performed using microsatellite markers and K-ras point mutations were analysed by dot blot hybridisation. The incidences of changes for polypoid and non-polypoid infiltrative types were 73% and 26% on 5q, 63% and 59% on 9p, 55% and 50% on 17p, and 20% and 18% on 18q, and 25% and 27% for K-ras mutations. Most importantly, we found the frequency of 5qLOH to be significantly higher with polypoid growth than in the non-polypoid infiltrative type (p<0.05), especially in extrahepatic duct carcinomas (p<0.05). The incidences of other genetic alterations (LOH at 9p, 17p, and 18q, and K-ras mutations) showed similar rates with both tumour types. The present data suggest that 5qLOH may have a close relation with polypoid growth in BDCs. (+info)
Results of radical resection for periampullary cancer.
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This report concerns 348 pancreatoduodenectomies, including 13 total pancreatectomies. Operative mortality over 30 years was 15%, operative mortality since 1962, 10%. Precise factors influencing operability, mortality, morbidity, and long-term palliation or cure are emphasized. The necessity for making a distinction among tumors arising in the ampulla of Vater, the intrapancreatic portion of the common bile duct, and the duodenum surrounding the papilla of Vater and carcinomas arising in the head of the pancreas is the most important factor in the approach to periampullary malignant tumors. Even with this large experience, the impression of the operating surgeon at the time of resection was incorrect in 10% of the patients in whom a reons who do not resect carcinomas arising in the head of the pancreas and who may have had less experience in this specialized field may be rejecting an even larger per cent of patients with more favorable periampullary malignant tumors. The influence of previous exploration, manipulation, and biopsy on morbidity, mortality, and survival is discussed. The significance of nodal involvement and residual tumor at the neck of the pancreas and the point of division of the common bile duct and the uncinate process is discussed. These data justify continued selective application of pancreatoduodenectomy for periampullary cancer and identify areas where further improvement can be made. (+info)
Is preventive resection of the extrahepatic bile duct necessary in cases of pancreaticobiliary maljunction without dilatation of the bile duct?
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BACKGROUND: No consensus has been reached on whether preventive resection of the extrahepatic bile duct is necessary in cases of pancreaticobiliary maljunction (PBM) without dilatation of the extrahepatic bile duct (undilated type). METHODS: Sixty-eight patients with PBM underwent corrective surgery and several clinical characteristics and pathological findings including K-ras point mutation were evaluated. RESULTS: Unlike dilated bile duct, none of the patients with undilated type duct had clinical symptoms in early childhood. In patients with either cystic or spindle type duct, amylase levels in the bile duct were >10(4) U/l, whereas those in patients with undilated type duct were <10(4) U/l. Postoperative scintigraphy of the biliary system of undilated type revealed no evidence of cholestasis. After surgery, eight patients with undilated type duct, in whom the bile duct had been preserved, had no further clinical symptoms and no evidence of malignancy. Bile duct tissue specimens revealed no hyperplasia, dysplasia or cancerous lesions and they had no K-ras mutation in undilated type. CONCLUSION: The results showed that there was little bile stasis, injury to the mucosa was mild and less genetic changes could be seen in patients with undilated type duct. Therefore, in patients without dilatation of bile duct and advanced cancer, cholecystectomy alone is sufficient. (+info)
Combined hepatocellular and cholangiocellular carcinoma in a dog.
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A transitional type of combined hepatocellular and cholangiocellular carcinoma developed in a 12-year-old male Yorkshire terrier dog. The tumor was histologically composed of both hepatocellular carcinoma and cholangiocellular carcinoma components, and both elements were closely intermingled. Intraluminal mucin accumulation in cytokeratin-positive tubular/glandular structures was observed within the cholangiocellular carcinoma components and this feature was useful histological marker for a differential diagnosis between combined hepatocellular and cholangiocellular carcinoma and a pseudoglandular type of hepatocellular carcinoma. This primary hepatic tumor is extremely rare in dogs. (+info)