Establishment and characterisation of six human biliary tract cancer cell lines.
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Human cell lines established from biliary tract cancers are rare, and only five have been reported previously. We report the characterisation of six new six biliary tract cancer cell lines (designated SNU-245, SNU-308, SNU-478, SNU-869, SNU-1079 and SNU-1196) established from primary tumour samples of Korean patients. The cell lines were isolated from two extrahepatic bile duct cancers (one adenocarcinoma of common bile duct, one hilar bile duct cancer), two adenocarcinomas of ampulla of Vater, one intrahepatic bile duct cancer (cholangiocarcinoma), and one adenocarcinoma of the gall bladder. The cell phenotypes, including the histopathology of the primary tumours and in vitro growth characteristics, were determined. We also performed molecular characterisation, including DNA fingerprinting analysis and abnormalities of K-ras, p15, p16, p53, hMLH1, hMSH2, DPC4, beta-catenin, E-cadherin, hOGG1, STK11, and TGF-betaRII genes by PCR-SSCP and sequencing analysis. In addition, we compared the genetic alterations in tumour cell lines and their corresponding tumour tissues. All lines grew as adherent cells. Population doubling times varied from 48-72 h. The culture success rate was 20% (six out of 30 attempts). All cell lines showed (i) relatively high viability; (ii) absence of mycoplasma or bacteria contamination; and (iii) genetic heterogeneity by DNA fingerprinting analysis. Among the lines, three lines had p53 mutations; and homozygous deletions in both p16 and p15 genes were found three and three lines, respectively; one line had a heterozygous missense mutation in hMLH1; E-cadherin gene was hypermethylated in two lines. Since the establishment of biliary tract cancer cell lines has been rarely reported in the literature, these newly established and well characterised biliary tract cancer cell lines would be very useful for studying the biology of biliary tract cancers, particularly those related to hypermethylation of E-cadherin gene in biliary tract cancer. (+info)
Adenosquamous carcinoma of the gallbladder warrants resection only if curative resection is feasible.
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BACKGROUND: Adenosquamous/squamous cell carcinoma of the gallbladder generally has been considered a lethal disease. The objective of this study was to clarify the effectiveness of resection for patients with adenosquamous/squamous cell carcinoma of the gallbladder. METHODS: Twenty-nine patients who underwent resection for either adenosquamous carcinoma (n = 28 patients) or squamous cell carcinoma (n = 1 patient) were analyzed retrospectively. Sixteen patients underwent radical resection, whereas the other patients underwent primary tumor resection alone. To elucidate the factors that influenced postresectional survival, 10 variables (age, gender, presence or absence of gallstones, size of the primary tumor, lymphatic vessel invasion, blood vessel invasion, perineural invasion, TNM stage, residual tumor status, and type of resection) were examined. RESULTS: Twenty-three patients (79.3%) were categorized with T3 or T4 tumors that invaded adjacent organs. The outcome after undergoing radical resection (cumulative 5-year survival rate, 48.6%) was significantly better compared with the outcome of patients after undergoing primary tumor resection alone (cumulative 3-year survival rate, 7.7%; P = 0.004). The outcome after undergoing resection was better in 14 patients who had no residual tumor (cumulative 5-year survival rate, 62.9%) compared with the outcome in 15 patients who had residual tumor (cumulative 5-year survival rate, 0%; P < 0.001). Univariate analysis revealed that residual tumor status (P < 0.001), type of resection (P = 0.004), patient age (P = 0.012), and blood vessel invasion (P = 0.017) were significant prognostic factors. Residual tumor status (P = 0.026) was the only significant independent prognostic factor. CONCLUSIONS: Adenosquamous/squamous cell carcinoma of the gallbladder warrants resection only if potentially curative (R0) resection is feasible. (+info)
Endoscopic transpapillary biopsies and intraductal ultrasonography in the diagnostics of bile duct strictures: a prospective study.
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BACKGROUND: In bile duct strictures, examination of wall layers by intraductal ultrasonography (IDUS) performed during endoscopic retrograde cholangiopancreatography (ERCP) may be diagnostically useful. METHODS: In the present study 60 patients with bile duct strictures of unknown aetiology were examined preoperatively by ERCP, including transpapillary biopsies and IDUS. Histopathological correlation was available for all patients undergoing these procedures. RESULTS: Postoperative diagnosis revealed 30 pancreatic carcinomas, 17 bile duct cancers, three gall bladder cancers, and 10 benign bile duct strictures. Using endoscopic transpapillary forceps biopsies (ETP), a correct preoperative diagnosis was achieved in 36 of 60 patients (60% of cases). Among the 50 malignant tumours, preoperative diagnosis by ETP revealed a sensitivity of 52% and a specificity of 100%. ERCP supplemented by IDUS allowed for correct preoperative diagnosis in 83% of cases (50 of 60 patients), which was significantly higher than the accuracy of ETP (p=0.008). By combining ETP with IDUS, a correct preoperative diagnosis was made in 59 of 60 patients resulting in an accuracy rate of 98%. CONCLUSIONS: Because of its low accuracy, exclusive use of ETP is not a reliable diagnostic tool for a definitive preoperative diagnosis of bile duct strictures. By combining IDUS and ETP with ERCP however, preoperative diagnostic accuracy can be improved substantially. (+info)
High resolution chromosome 3p, 8p, 9q and 22q allelotyping analysis in the pathogenesis of gallbladder carcinoma.
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Our recent genome-wide allelotyping analysis of gallbladder carcinoma identified 3p, 8p, 9q and 22q as chromosomal regions with frequent loss of heterozygosity. The present study was undertaken to more precisely identify the presence and location of regions of frequent allele loss involving those chromosomes in gallbladder carcinoma. Microdissected tissue from 24 gallbladder carcinoma were analysed for PCR-based loss of heterozygosity using 81 microsatellite markers spanning chromosome 3p (n=26), 8p (n=14), 9q (n=29) and 22q (n=12) regions. We also studied the role of those allele losses in gallbladder carcinoma pathogenesis by examining 45 microdissected normal and dysplastic gallbladder epithelia accompanying gallbladder carcinoma, using 17 microsatellite markers. Overall frequencies of loss of heterozygosity at 3p (100%), 8p (100%), 9q (88%), and 22q (92%) sites were very high in gallbladder carcinoma, and we identified 13 distinct regions undergoing frequent loss of heterozygosity in tumours. Allele losses were frequently detected in normal and dysplastic gallbladder epithelia. There was a progressive increase of the overall loss of heterozygosity frequency with increasing severity of histopathological changes. Allele losses were not random and followed a sequence. This study refines several distinct chromosome 3p, 8p, 9q and 22q regions undergoing frequent allele loss in gallbladder carcinoma that will aid in the positional identification of tumour suppressor genes involved in gallbladder carcinoma pathogenesis. (+info)
A case of gallbladder cancer associated with pancreaticobiliary maljunction.
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We report a case of gallbladder cancer associated with pancreaticobiliary maljunction. The patient was a 60-year-old woman who consulted a local doctor because of discomfort in the right hypochondriac region. Abdominal ultrasonography (US) showed a gallbladder abnormality, and she was referred to Kurume University Hospital, where she was hospitalized for further study and surgery. Abdominal US revealed a sessile tumor with an irregular surface in the fundus of the gallbladder. The internal echo of the tumor was nonhomogeneous, and the structure of the gallbladder wall was partly torn. The common bile duct and the left intrahepatic bile duct were dilated. Abdominal computed tomography (CT) showed an elevated lesion with the same degree of imaging effect as that of the liver on the peritoneal side of the fundus of the gallbladder. The structure of the gallbladder was preserved, and the gallbladder was well demarcated from the surrounding tissue. No hepatic or lymph node metastases were noted. Endoscopic retrograde cholangiopancreatography (ERCP) visualized the pancreaticobiliary maljunction where the pancreatic duct joined the bile duct, entering an approximately 2-cm-long common channel. Dilatation of the common bile duct and intrahepatic bile ducts was observed and diagnosed as the IV-A type according to the Toya classification. Abdominal angiography in the arterial phase showed dilatation of the cystic artery and hyperplasia of vessels but no apparent encasement. In the venous phase, a deep-staining tumor was observed. From the above findings, we made a diagnosis of gallbladder cancer complicating pancreaticobiliary maljunction, and performed an operation. Since intraoperative US showed that the outermost layer of the gallbladder was in part ill-demarcated, we diagnosed the depth of penetration as ss, and performed cholecystectomy and bile duct resection and hepatic resection (S4a and S5), and lymphnode dissection (D2; dissection of groups 1 and 2 lymphnodes). The resected specimen grossly showed a papillomatous lesion with a cauliflower-like surface. The histopathologic diagnosis was papillary adenocarcinoma, depth ss, stage II. Tumor cells proliferated in a papillomatous pattern and were mostly confined to the muscular coat but partly infiltrated into the subserosal coat. In the diagnosis of pancreaticobiliary maljunction, it is crucial to consider complicating gallbladder cancer. (+info)
Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma.
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BACKGROUND: To the authors' knowledge, the significance of postoperative adjuvant chemotherapy in pancreaticobiliary carcinoma has not yet been clarified. A randomized controlled study evaluated the effect of postoperative adjuvant therapy with mitomycin C (MMC) and 5-fluorouracil (5-FU) (MF arm) versus surgery alone (control arm) on survival and disease-free survival (DFS) for each specific disease comprising resected pancreaticobiliary carcinoma (pancreatic, gallbladder, bile duct, or ampulla of Vater carcinoma) separately. METHODS: Between April 1986 and June 1992, a total of 508 patients with resected pancreatic (n = 173), bile duct (n = 139), gallbladder (n = 140), or ampulla of Vater (n = 56) carcinomas were allocated randomly to either the MF group or the control group. The MF group received MMC (6 mg/m(2) intravenously [i.v.]) at the time of surgery and 5-FU (310 mg/m(2) i.v.) in 2 courses of treatment for 5 consecutive days during postoperative Weeks 1 and 3, followed by 5-FU (100 mg/m(2)orally) daily from postoperative Week 5 until disease recurrence. All patients were followed for 5 years. RESULTS: After ineligible patients were excluded, 158 patients with pancreatic carcinoma (81 in the MF group and 77 in the control group), 118 patients with bile duct carcinoma (58 in the MF group and 60 in the control group), 112 patients with gallbladder carcinoma (69 in the MF group and 43 in the control group), and 48 patients with carcinoma of the ampulla of Vater (24 in the MF group and 24 in the control group) were evaluated. Good compliance (> 80%) was achieved with MF treatment. The 5-year survival rate in gallbladder carcinoma patients was significantly better in the MF group (26.0%) compared with the control group (14.4%) (P = 0.0367). Similarly, the 5-year DFS rate of patients with gallbladder carcinoma was 20.3% in the MF group, which was significantly higher than the 11.6% DFS rate reported in the control group (P = 0.0210). Significant improvement in body weight compared with the control was observed only in patients with gallbladder carcinoma. There were no apparent differences in 5-year survival and 5-year DFS rates between patients with pancreatic, bile duct, or ampulla of Vater carcinomas. Multivariate analyses demonstrated a tendency for the MF group to have a lower risk of mortality (risk ratio of 0.654; P = 0.0825) and recurrence (risk ratio of 0.626; P = 0.0589). The most commonly reported adverse drug reactions were anorexia, nausea/emesis, stomatitis, and leukopenia, none of which were noted to be serious. CONCLUSIONS: The results of the current study indicate that gallbladder carcinoma patients who undergo noncurative resections may derive some benefit from systemic chemotherapy. However, alternative modalities must be developed for patients with carcinomas of the pancreas, bile duct, or ampulla of Vater. (+info)
Gingival metastasis from gallbladder cancer.
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Gallbladder cancer is generally diagnosed at an advanced stage. The liver is the most commonly invaded organ by direct extension and/or metastasis, followed by regional lymph nodes. Oral soft tissue metastasis is extremely unusual. This report describes the case of a 62-year-old woman diagnosed with advanced metastatic gallbladder cancer, who initially presented with abdominal pain. Diagnosis of gallbladder cancer was made about 3 months after her symptoms developed, when a laparoscopic cholecystectomy was performed because of the suspicion of gallstones. Liver metastasis was also discovered during surgery. A postoperative investigation revealed additional lung and bone metastases. A visible left gingival tumor was found on physical examination and was confirmed as gallbladder cancer metastasis by compatible histopathology 1 month after surgery. The patient responded poorly to chemotherapy and unfortunately died 5 months after the diagnosis. The clinical presentation of gallbladder cancer was relatively typical, apart from the unusual gingival metastasis. The medical literature contains quite a few examples of metastatic lesions located strictly in the oral soft tissue, however no case of gallbladder cancer metastasizing to the oral soft tissue has been previously reported. (+info)
Comparative analysis of Helicobacter DNAs and biliary pathology in patients with and without hepatobiliary cancer.
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Several Helicobacter species have recently been isolated from the bile and hepatobiliary systems of murine species, and are well recognized as a pathogen of the hepatobiliary disorder. This study was planned to investigate whether Helicobacter species possess a causative potential for human hepatobiliary disease, especially for hepatobiliary carcinogenesis. Bile and hepatobiliary tissue samples from 19 patients with hepatobiliary cancer and 19 patients with benign biliary diseases were subjected to polymerase chain reaction analyses for the detection of Helicobacter DNAs. Using a proliferating cell nuclear antigen (PCNA) staining technique, we also investigated the biliary epithelial cell kinetics with special reference to the presence of Helicobacter DNAs in the hepatobiliary system. We found that Helicobacter DNAs were positive in 10 (52.6%) of the 19 patients with hepatobiliary cancer. The incidence was significantly higher than that (15.7%) in the benign cases (P = 0.03). The PCNA labeling index in the biliary epithelium in Helicobacter DNA-positive patients was statistically higher than that in Helicobacter DNA-negative ones, regardless of whether the patient was suffering from hepatobiliary cancer and/or biliary inflammation. A close correlation between the presence of Helicobacter DNAs and an elevation of the PCNA labeling index in the biliary epithelium was demonstrated by multiple regression analysis. Our findings suggest that Helicobacter species may play a role in the pathogenesis of hepatobiliary cancer through an acceleration of biliary cell kinetics. (+info)