Down stream involvement of the bile duct in hepatolithiasis. (73/1040)

OBJECTIVE: To evaluate the down stream involvement of the bile duct in hepatolithiasis. METHODS: Mechanical damage to bile duct epithelia and long standing cholangitis as result of hepatolithiasis play an important role in the carcinogenesis of bile duct epithelia and stricture of the intra- and extra-hepatic bile duct. Macromorphological and microscopic changes in bile duct mucosa of 100 consecutive patients with hepatolithiasis were investigated using intra- or post-operative cholangioscopy. Biopsy specimens of lesions obtained during cholangioscopy were studied with immunohistochemical staining and flow cytometry to determine proliferative activity and DNA content. Five cases of well-proven cholangiocarcinoma were simultaneously studied as controls. RESULTS: Of the 100 patients, those with chronic cholangitis accounted for 86% (86/100), proliferative lesions 11% (11/100), adenomatous polyps 1% (1/100), and adenocarcinoma 2% (2/100). The obvious mucosal lesion associated with hepatolithiasis was located down-stream of the bile duct, predominantly in the hilar region, e.g. orifices of the right/left hepatic duct and common hepatic duct (73% mucosa lesions in the hilar region). The intensity of cancer embryonic antigen stain and the proliferative cell nuclear antigen index increased with the development of bile duct lesions. Aneuploid DNA presented mainly in the high degree malignant adenocarcinomas (> 80% of cases). CONCLUSIONS: The obvious mucosal lesions associated with hepatolithiasis were located down-stream of the bile duct, predominantly in the hilar region (73% of mucosal lesions). The proliferative activity of examined bile duct mucosa lesions increased with the development of pathological deterioration, which may contribute to the development of hilar bile duct stricture and hilar cholangiocarcinoma.  (+info)

Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. (74/1040)

BACKGROUND: Tumors with combined hepatocellular and cholangiocellular features are well known histopathologically but their clinical behavior is poorly understood. The objectives of the current study were to define the demographic profile of the patients in whom these uncommon tumors occur and to evaluate treatment outcome in comparison with that in patients with either hepatocellular carcinoma (HCC) or peripheral cholangiocarcinoma (CC) alone. METHODS: Twenty-seven patients with combined tumors were identified from a prospective database. Pathologic specimens were analyzed to confirm the diagnosis. Demographics, clinical data, and survival were analyzed. Outcome after resection was compared with that of patients with CC and with a matched group of patients with HCC. RESULTS: The gender distribution of the combined tumors (52% men and 48% women) was intermediate between HCC (67% men and 33% women) and CC (30% men and 70% women) (P = 0.03). The incidence of positive hepatitis B or C serology and cirrhosis was similar in patients with combined tumors and those with CC (15% and 0% vs. 13% and 4%, respectively); similarly, patients of Asian heritage constituted 7% and 9%, respectively, of the patients with these tumors. By contrast, cirrhosis (41%) and positive hepatitis serology (56%) were far more common in patients with HCC, and 19% of these patients were of Asian heritage. Twenty-one of 27 patients with combined tumors (78%) underwent resection. All 6 patients with combined tumors that were not amenable to resection died of disease within 18 months. After resection, the 5-year survival was lowest in patients with combined tumors (24%) but was not significantly different from that in patients with CC (33%) or HCC (37%). The liver was the most common site of recurrence in all three groups. CONCLUSIONS: The demographic and clinical features of patients with combined tumors were most similar to those of patients with CC. Most important, combined tumors were not found to be associated with chronic liver disease; consequently, the resectability rate was higher for these tumors than typically is reported for HCC. Resection was associated with long-term survival in some patients, but recurrent hepatic disease was common. The presence of cholangiocellular differentiation appeared to worsen the prognosis when compared with pure HCC, although this difference did not reach statistical significance.  (+info)

Worldwide trends in mortality from biliary tract malignancies. (75/1040)

BACKGROUND: Intrahepatic cholangiocarcinomas are malignant tumors arising from the intrahepatic biliary tract. The pathogenesis of these tumors remains unknown. Although there is a marked global variation in prevalence, some recent studies have suggested an increase in mortality from intrahepatic cholangiocarcinoma in several regions of low endemicity. As the study of mortality trends may yield clues to possible etiological factors, we analyzed worldwide time trends in mortality from biliary tract malignancies. METHODS: Annual age-standardized rates for individual countries were compiled for deaths from biliary tract malignancies using the WHO database. These data were used to analyze gender and site-specific trends in mortality rates. RESULTS: An increasing trend for mortality from intrahepatic cholangiocarcinoma was noted in most countries. The average estimated annual percentage change (EAPC) in mortality rates for males was 6.9 +/- 1.5, and for females was 5.1 +/- 1.0. Increased mortality rates were observed in all geographic regions. Within Europe, increases were higher in Western Europe than in Central or Northern Europe. In contrast, mortality rates for extrahepatic biliary tract malignancies showed a decreasing trend in most countries, with an overall average EAPC of -0.3 +/- 0.4 for males, but -1.3 +/- 0.4 for females. CONCLUSIONS: There has been a marked global increase in mortality from intrahepatic, but not extra-hepatic, biliary tract malignancies.  (+info)

Hepatobiliary inflammation, neoplasia, and argyrophilic bacteria in a ferret colony. (76/1040)

Hepatobiliary disease was diagnosed in eight of 34 genetically unrelated cohabitating pet ferrets (Mustela putorios furo) during a 7-year period. The eight ferrets ranged in age from 5 to 8 years and exhibited chronic cholangiohepatitis coupled with cellular proliferation ranging from hyperplasia to frank neoplasia. Spiral-shaped argyrophilic bacteria were demonstrated in livers of three ferrets, including two with carcinoma. Sequence analysis of a 400-base pair polymerase chain reaction product amplified from DNA derived from fecal bacteria from one ferret demonstrated 98% and 97% similarity to Helicobacter cholecystus and Helicobacter sp. strain 266-1 , respectively. The clustering of severe hepatic disease in these cohabitating ferroes suggests a possible infectious etiology. The role of Helicobacter species and other bacteria in hepatitis and/or neoplasia in ferrets requires further study.  (+info)

Tamoxifen (TMX)/Fas induced growth inhibition of human cholangiocarcinoma (HCC) by gamma interferon (IFN-gamma). (77/1040)

OBJECTIVES: To evaluate the response of human cholangoicarcinoma cells to TMX treatment through the Fas pathway by pretreatment with IFN-gamma. SUMMARY BACKGROUND DATA: Cholangiocarcinoma remains one of the most difficult tumors to treat in clinical medicine. Currently, there are no effective chemotherapy treatments for this disease. Surgery offers the only opportunity for a cure, with the majority of patients failing to qualify for such treatment. This study seeks to evaluate a potential new modality for treatment of this disease. METHODS: Human cholangiocarcinoma cells were treated with anti Fas mab and sorted to two populations (Fas-positive and Fas-negative) by FAC analysis. In vitro individual cell populations were pretreated with IFN-gamma 250 units/mL x 18hs. The treated cells assayed for caspase 3, 7, 8, Bak, and for apoptosis with Annexin V after treatment with or without TMX. In Vivo 2 x 106 5 SK-ChA-1 Fas-negative cells were injected into nude mice for development of tumor xenografts. Mice received either no treatment or intra tumor IFN-gamma and/or intra peritoneal TMX. RESULTS: More than 90% (90% +/- 3.5%) of Fas-positive and 70% (71 +/- 2.3%) of Fas-negative cells underwent apoptosis after TMX treatment when pretreated with IFN-gamma. In contrast, TMX alone and IFN-gamma alone stimulated apoptosis by only 22% (22 +/- 3%) P <.00013, and 17% (17 +/- 2%) P <.0001 in Fas-ve cells respectively. In vivo human cholangiocarcinomas xenograft growth was significantly inhibited by a combination of TMX + IFN-gamma compared to controls P <.0007. CONCLUSION: TMX exposure to human cholangiocarcinoma after pretreatment with IFN-gamma allows for induction of apoptosis in vitro and significant inhibition tumor xenograft growth. The combination of these two compounds may provide novel treatment regimen for cholangiocarcinoma.  (+info)

Extreme left hepatic lobar atrophy in a case with hilar cholangiocarcinoma. (78/1040)

We describe an unusual case of extreme hepatic left lobar atrophy with hilar cholangiocarcinoma. A 67-year-old woman was referred to Nippon Medical School with obstructive jaundice. On admission, computed tomography revealed dilated intrahepatic bile ducts and a defect in the area drained by the left side of the middle hepatic vein. A Spiegel lobe was demonstrated, but the left lobe could not be detected to the left side of the gallbladder. Percutaneous transhepatic cholangiography was performed and demonstrated obstruction of the intrahepatic bile duct at the hepatic hilum. A drainage catheter was left in place. Angiography revealed that the left hepatic artery was present, but there was narrowing of the left portal vein. A diagnosis of agenesis of the left hepatic lobe with hilar cholangiocarcinoma was made. At surgery, the left lobe appeared extremely atrophic without atrophy of the Spiegel lobe. The right anterior branches of the hepatic artery and portal vein had been invaded by carcinoma, so a left trisegmentectomy was performed. Final pathology was advanced hilar cholangiocarcinoma with invasion of the hepatic parenchyma, portal vein, and nervous system. The left lobe was atrophic without hepatolithiasis. The left portal vein was narrow distal to the Spiegel branch. The serum total bilirubin concentration was elevated postoperatively, and the patient was treated for hepatic failure. The patient died of pneumonia without recurrence 7 months after surgery. This rare case of extreme hepatic left lobar atrophy with hilar cholangiocarcinoma was successfully treated by left trisegmentectomy. Preoperative portal embolization was unnecessary because the left lobe was already atrophic.  (+info)

Establishment and characterisation of six human biliary tract cancer cell lines. (79/1040)

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)

A long-term survivor of intrahepatic cholangiocarcinoma with lymph node metastasis: a case report. (80/1040)

We describe a case of intrahepatic cholangiocarcinoma (ICC) in a 50-year-old man. A well-defined, hypoechoic tumor, 3.5 cm in greatest diameter, was detected in the left medial segment of the liver with ultrasonography. Celiac angiography showed staining at the same location. Computed tomography revealed lymph node swelling around the head of the pancreas. On October 10, 1993, the patient underwent partial hepatectomy with pancreatoduodenectomy and lymph node dissection around the hepatoduodenal ligament and along the common hepatic artery. Postoperative histopathological examination showed a moderately differentiated tubular adenocarcinoma which had metastasized to the dissected lymph nodes at the posterior surface of the head of the pancreas and at the root of the middle colic artery. Eight years after surgery, the patient is alive and well with no sign of recurrence. Immunohistochemical staining showed ductal-type mucin core protein-1 expression in the tumor, which indicates more favorable survival after surgery. Patients with ICC and lymph node metastasis are considered to have poor prognosis; however, further study of the characteristics of ICC with lymph node metastasis is needed.  (+info)