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At least 19 recordsLinked to original sources
PubMed2006

Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States.

Cholangiocarcinomas are topographically categorized as intrahepatic or extrahepatic by the International Classification of Diseases for Oncology (ICD-O). Although hilar cholangiocarcinomas (Klatskin tumors) are extrahepatic cholangiocarcinomas, the second edition of the ICD-O (ICD-O-2) assigned them a histology code 8162/3, Klatskin, which was cross-referenced to intrahepatic cholangiocarcinoma. Recent studies in the United States that included this code (8162/3, Klatskin) with intrahepatic cholangiocarcinoma reported an increasing incidence of intrahepatic cholangiocarcinoma and a decreasing incidence of extrahepatic cholangiocarcinoma. To investigate the impact of this misclassification on site-specific cholangiocarcinoma incidence rates, we calculated annual percent changes (APCs) with data from the Surveillance, Epidemiology, and End Results (SEER) program using a Poisson regression model that was age-adjusted to the year 2000 U.S. population. All statistical tests were two-sided. During 1992-2000, when SEER used ICD-O-2, 1710 intrahepatic cholangiocarcinomas, 1371 extrahepatic cholangiocarcinomas, and 269 hilar cholangiocarcinomas identified by code 8162/3, Klatskin were diagnosed. Ninety-one percent (246 of 269) of the hilar cholangiocarcinomas were incorrectly coded as intrahepatic cholangiocarcinomas, resulting in an overestimation of intrahepatic cholangiocarcinoma incidence by 13% and underestimation of extrahepatic cholangiocarcinomas incidence by 15%. However, even after the exclusion of tumors that were coded to the histology code 8162/3, Klatskin, age-adjusted annual intrahepatic cholangiocarcinoma incidence increased during this period (APC = 4%, 95% confidence interval = 2% to 6%, P<.001).

Adult↗
PubMed2004

Expression of epidermal growth factor receptor, apomucins, matrix metalloproteinases, and p53 in rat and human cholangiocarcinoma: appraisal of an animal model of cholangiocarcinoma.

OBJECTIVE: We sought to determine the expression of molecular markers in an animal model of cholangiocarcinoma compared with those in human cholangiocarcinoma. SUMMARY BACKGROUND DATA: Cholangiocarcinoma is a rare disease characterized by early intrahepatic and extrahepatic spread, which seriously limits the efficacy of surgery. Establishing an experimental model to study the cholangiocarcinogenesis is desirable. METHODS: Sprague-Dawley rats weighing 300 +/- 50 g were used for the study group. The animals were given 0.3% thioacetamide in tap water continuously. Thirty mass-forming peripheral cholangiocarcinoma patients also were studied. Expression of epidermal growth factor receptor (EGFR), MUC1, MUC2, MUC5AC, MMP-2, MMP-9, and p53 in both human and experimental rat cholangiocarcinoma was examined using immunohistochemistry. RESULTS: Using thioacetamide 0.3% as a hepatoxin to induce cholangiocarcinoma in rats, microfoci of cancerous cells were detected from 12 weeks, and all experimental rats displayed diffuse mass-forming cholangiocarcinoma after 24 weeks. EGFR was strongly expressed in 14 (47%) of 30 human cholangiocarcinoms and 24 (100%) of 24 rat cholangiocarcinomas, respectively. MUC1 was strongly expressed in all human and rat cholangiocarcinomas, whereas MUC2 and MUC5AC were focally and weakly expressed. MMP-2 and MMP-9 were strongly expressed in 22 (73%) of 30 human cholangiocarcinomas and 24 (100%) of 24 rat cholangiocarcinomas, respectively. p53 overexpression was detected in 9 (30%) of 30 human cholangiocarcinoma and none of the rat cholangiocarcinoma, respectively. CONCLUSIONS: The expression of EGFR, apomucins, MMPs, and p53 in rat cholangiocarcinoma was strongly homologous to human cholangiocarcinoma. Thioacetamide-induced cholangiocarcinoma in rats provides an excellent model for investigating cholangiocarcinogenesis in vivo.

Animals↗
PubMedDate not supplied

Comparing combined hepatocellular-cholangiocarcinoma and cholangiocarcinoma: a clinicopathological study.

BACKGROUND/AIMS: Combined hepatocellular-cholangiocarcinoma is a rare subtype of primary liver cancer. To clarify the significance of this tumor, we conducted the present study to investigate the clinicopathological characteristics. As well, a comparison between this tumor and cholangiocarcinoma was made to determine whether these two types of liver cancers are closely related. METHODOLOGY: Seventeen cases of combined hepatocellular-cholangiocarcinoma and 104 cases of cholangiocarcinoma were included. Patients were evaluated on the basis of age, gender, viral hepatitis markers, tumor markers, laboratory data, indocyanine green test, tumor location, histological differentiation, lymph node involvement, and organ metastasis. In addition, the presenting symptoms at admission were also recorded. Data was analyzed using the chi 2 test and Student's t test and differences between the curves were tested using the two-tailed log-rank test. RESULTS: Combined hepatocellular-cholangiocarcinoma was found to be more prevalent in males. In addition, the combined hepatocellular-cholangiocarcinoma patients had lower serum bilirubin, ALP levels (p < 0.05), and more poor differentiation (p < 0.05). Also, the presenting symptoms of combined hepatocellular-cholangiocarcinoma patients were different from those of cholangiocarcinoma patients with the former a lower incidence of fever, chills, jaundice and a higher incidence of fatigue and weakness. CONCLUSIONS: The clinicopathological features of combined hepatocellular-cholangiocarcinoma were different from those of cholangiocarcinoma with more advanced histological differentiation, more prevalent in males, and lower levels of serum bilirubin and ALP. These characteristic features may help us in diagnosing combined hepatocellular-cholangiocarcinoma in patients with suspected cholangiocarcinoma.

Alkaline Phosphatase↗
PubMed1995

Imaging of intrahepatic cholangiocarcinoma: 1. Peripheral cholangiocarcinoma.

Cholangiocarcinoma is the second most common primary hepatic malignant tumor after hepatocellular carcinoma, accounting for 5-30% of all primary hepatic malignant tumors [1]. Intrahepatic cholangiocarcinomas can be classified as peripheral cholangiocarcinoma, which originates from an interlobular biliary duct, or as hilar cholangiocarcinoma, which originates from a main hepatic duct or from the bifurcation of the common hepatic duct. Intrahepatic cholangiocarcinomas account for only about half of cholangiocarcinomas, and this pictorial essay focuses only on the peripheral form of the disease. Clinically, therapeutically, and radiologically, these two types of cholangiocarcinomas differ. Features suggestive of the diagnosis of peripheral cholangiocarcinoma can be shown by sonography, CT, and MR imaging. Cholangiography and angiography have a limited role in evaluating this neoplasm that manifests as a focal mass. This essay reviews the appearances of peripheral cholangiocarcinoma and discusses the various imaging techniques that can be used to evaluate this unusual tumor that is often resectable and potentially curable.

Adult↗
PubMed1987

Expression of ABH and Lewis blood group antigens in combined hepatocellular-cholangiocarcinoma. Possible evidence for the hepatocellular origin of combined hepatocellular-cholangiocarcinoma.

Expression of ABH, Lewis, and sialyl Lea antigens was studied in five combined hepatocellular-cholangiocarcinomas. Formalin-fixed liver tissues were immunostained for those antigens using well-characterized monoclonal antibodies and an avidin-biotin-peroxidase complex (ABC) method. Results were compared with those obtained in normal liver tissues and cholangiocarcinomas, and also with the previous observations of the authors on hepatocellular carcinomas. Although not detected in normal parenchymal liver cells, A, H, Lewis, and sialyl Lea antigens were found in combined hepatocellular-cholangiocarcinoma cells. Incompatible A antigen also was detected in one blood type O patient. Distribution and intensity of the antigens were similar to those in hepatocellular carcinomas and different from those in cholangiocarcinomas. No preferential accumulation of blood-group antigens could be found in the area of cholangiocarcinoma-like differentiation of the combined hepatocellular-cholangiocarcinoma. The observations suggested that Regional morphological differentiation of the hepatocellular-cholangiocarcinoma might not be always associated with the change in the expression of the blood group antigens. Moreover, the expression was essentially the same between the hepatocellular-cholangiocarcinoma and the typical hepatocellular carcinoma. The hepatocellular-cholangiocarcinoma, therefore could be a variant of the hepatocellular carcinoma.

ABO Blood-Group System↗
PubMed2001

Fas counterattack in cholangiocarcinoma: a mechanism for immune evasion in human hilar cholangiocarcinomas.

AIM: To investigate FasL expression in hilar cholangiocarcinoma tissues and cultured cholangiocarcinoma cells, and to assess its ability to induce apoptosis. METHODS: We studied the expression of FasL by human hilar cholangiocaroinomas tissues by immunohistochemistry, and the QBC939 cholangiocarcinoma cell line by RT-PCR, immunohistochemistry, and Western Blot. TUNEL and flow cytometry were used to detect apoptotic cells. RESULTS: Prevalent expression of FasL was detected in 39 resected hilar cholangiocarcinoma tissues. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumor. FasL mRNA and protein expressions in cholangiocarcinoma cells could induce Jurkat cells. CONCLUSION: Hilar cholangiocarcinomas may elude immunological surveillance by inducing, via Fas/FasL system, the apoptosis of activated lymphocytes.

Apoptosis↗
PubMed1996

A human combined hepatocellular and cholangiocarcinoma cell line (KMCH-2) that shows the features of hepatocellular carcinoma or cholangiocarcinoma under different growth conditions.

BACKGROUND/AIMS: Combined hepatocellular and cholangiocarcinoma is a rare tumor of the liver, and its histogenesis remains unclear. The authors addressed this issue in the current article. METHODS: A specimen aseptically obtained from the surgically resected combined hepatocellular and cholangiocarcinoma was processed for primary culture. The morphologic features of the established cell line cultured on a plastic dish and in type I collagen gel matrix, and transplanted in nude mice were examined. RESULTS: The authors established a new human combined hepatocellular and cholangiocarcinoma cell line, designated KMCH-2, from a 40-year-old Japanese man. KMCH-2 cells on a plastic dish proliferated in a monolayered sheet with a population doubling time of 32 to 44 h. KMCH-2 expressed functional characteristics of hepatocellular carcinoma, such as albumin synthesis at protein and mRNA levels, but were poorly differentiated in morphology, showing an overlap of features with cholangiocarcinoma. KMCH-2 cells cultured within type I collagen gel matrix proliferated, forming compact to vaguely trabecular and pseudoglandular arrangements, and differentiated to show morphological characteristics of hepatocellular carcinoma unlike the cells on a plastic dish. Mucin production was not detected in KMCH-2 cells in vitro. Subcutaneous tumors which developed in nude mice injected with KMCH-2 cells represented features of adenocarcinoma with mucin production. CONCLUSIONS: The present results revealed the presence of an albumin-producing human hepatic neoplastic cell, such as KMCH-2, that can differentiate to show not only the features of hepatocellular carcinoma but also those of cholangiocarcinoma under certain growth conditions.

Adult↗
PubMed1995

Imaging of intrahepatic cholangiocarcinoma: 2. Hilar cholangiocarcinoma.

Hilar cholangiocarcinoma (also called Klatskin's tumor) is more common than peripheral cholangiocarcinoma. Sonography, CT, MR imaging, angiography, and cholangiography can suggest the diagnosis, but the major issue of imaging with this tumor is to determine whether the tumor is resectable. The anatomic location of hilar cholangiocarcinoma makes resection difficult, so that surgical exploration of patients with this condition should be undertaken only when preoperative evaluation has shown a potential for curative resection. Preoperative assessment of resectability of hilar cholangiocarcinoma is often extensive, requiring several types of imaging. This pictorial essay reviews the imaging features of hilar cholangiocarcinoma. The role of imaging in the preoperative planning, with specific emphasis on staging extent of disease, including hepatic and vascular involvement, is discussed and illustrated.

Adult↗
PubMed2006

Clinicopathologic features of patients with intrahepatic cholangiocarcinoma who are seropositive for alpha-fetoprotein-L3 and those with combined hepatocellular and cholangiocarcinoma.

BACKGROUND: Some patients who are seropositive for lectin-reactive alpha-fetoprotein (AFP-L3) have intrahepatic cholangiocarcinoma (ICC). There have been no studies regarding the features of ICC patients seropositive for AFP-L3. Thus, the purpose of the present paper was to compare the features of ICC patients from the viewpoint of two different tumor markers, AFP-L3 and carbohydrate antigen (CA) 19-9. METHODS: The ICC patients who underwent hepatectomy (n = 51) were divided into three groups, and their clinicopathologic features were compared: (i) group A, seropositive for AFP-L3 >or= 15%; (ii) group B, seropositive for CA 19-9 >or= 37 U/mL; and (iii) group C, seronegative for both AFP-L3 and CA 19-9. The features of combined hepatocellular and cholangiocarcinoma (n = 11) were also studied. RESULTS: Group A had a higher positivity rate for hepatitis viruses than group B (60%vs 20%, P < 0.05). More patients in group A were misdiagnosed as having hepatocellular carcinoma (HCC) at surgery (70%vs 5.7%, P < 0.001) who also had chronic liver disease (80%vs 25.7%, P < 0.01) than in group B. Seven, 10 and 11 of the 11 patients with combined hepatocellular and cholangiocarcinoma were seropositive for AFP-L3, CA 19-9 and hepatitis viruses, respectively. Ten were diagnosed as having HCC at surgery and nine had chronic liver disease. CONCLUSIONS: Patients with ICC seropositive for AFP-L3 and those with combined hepatocellular and cholangiocarcinoma have features close to HCC. The present study has, for the first time, identified a subgroup of ICC patients, seropositive for AFP-L3, having features close to HCC that are very different from those of the classical ICC patients seropositive for CA 19-9.

Adult↗
PubMed2004

Rhabdoid cholangiocarcinoma: a variant of cholangiocarcinoma with aggressive behavior.

A rhabdoid cholangiocarcinoma is a very rare variant of sarcomatous cholangiocarcinomas. Here, we report a vimentin positive cholangiocarcinoma showing rhabdoid features in the entire tumor, with a very aggressive behavior. A 41-year-old woman was admitted to our hospital due to a huge hepatic mass. The resected liver revealed a 17 x 15 cm sized solid mass with extensive necrosis and an infiltrative border. On microscopic examination, the entire tumor was composed of loosely cohesive round to polygonal cells, with rhabdoid features having abundant eosinophilic glassy cytoplasm and eccentrically located vesicular nuclei. Some tumor cells contained intracytoplasmic mucin vacuoles, but definite areas of glandular differentiation or spindle cell were not found. Immunohistochemical staining showed a diffuse strong positive reaction to pan-cytokeratin and vimentin, and focal positivity for the carcinoembryonic antigen. Other immunohistochemical stainings for cytokeratin 7, cytokeratin 20, S-100 protein, HMB-45, desmin, alpha-smooth muscle actin, c-kit, CD34, alpha-fetoprotein, anti-hepatocyte antigen, chromogranin and synaptophysin were all negative. After two months, the patient developed a local recurrence along the resection margin, and multiple hematogenous metastases to the lung and liver were seen on the follow-up CT scan.

Adult↗
PubMed2006

Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

PURPOSE: Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare primary hepatic neoplasm (PHN) with features of both hepatocellular and biliary differentiation. We compared the outcome of hepatic resection in patients with HCC-CC, those with hepatocellular carcinoma (HCC), and those with cholangiocarcinoma (ICC). METHODS: Between November 1994 and December 2003, 952 patients underwent hepatic resection for a PHN. RESULTS: The incidence of HCC-CC was 3.5%. Hepatitis B surface antigen was positive in 51.2% of these patients and the HCV antibody was positive in 12.2%. Positive hepatitis serology was more common in the HCC group (66.7%). The prevalence of underlying liver cirrhosis was significantly lower in the ICC group (7.8%) than in the HCC (49%) and HCC-CC (41.5%) groups (P < 0.0001). The median overall survival periods after hepatic resection of HCC-CC, HCC, and ICC were 47.3, 71.7, and 21.5 months, respectively (P < 0.0001). The median disease-free survival (DFS) periods after hepatic resection for HCC-CC, HCC, and ICC were 23.4, 68.2, and 15.5 months, respectively (P < 0.0001). CONCLUSION: Patients with transitional type HCC-CC had significantly poorer survival rates than those with HCC, after hepatic resection. Therefore, a more aggressive treatment modality should be explored to improve the survival rate of these patients.

Adolescent↗
PubMed1999

Evaluation and endoscopic palliation of cholangiocarcinoma. Management of cholangiocarcinoma.

Patients with a cholangiocarcinoma usually develop symptoms of biliary obstruction which dominate the course of their illness. At presentation, the diagnosis may be difficult to establish due to the desmoplastic nature of this tumor. Location and extent of the tumor, however, are more effectively evaluated by current radiologic techniques. Following these staging procedures, most patients are found to be unsuitable for curative resection. Therefore, establishing effective biliary drainage to relieve symptoms of obstruction becomes the most critical therapeutic goal in these patients. In the past, surgical biliary bypass procedures were advocated, but were associated with high perioperative morbidity and mortality rates. Endoscopic biliary stenting produces quick and effective relief of symptoms from biliary obstruction due to cholangiocarcinoma. Initially, successful biliary drainage is possible in most patients. However, subsequent stent occlusion or spread of tumor into nonstentable intrahepatic ducts leads to recurrent jaundice. Local therapies including (192)Ir brachytherapy and photodynamic therapy may prevent or postpone these problems.

Bile Duct Neoplasms↗
PubMed1993

Hepatitis C virus antibody in patients with primary liver cancer (hepatocellular carcinoma, cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma) in Japan.

BACKGROUND: In hepatocellular carcinoma (HCC), a high prevalence of hepatitis C virus antibody (anti-HCV) has been reported, indicating that it may be an important etiologic factor in the pathogenesis of HCC. In this study, the authors investigated the prevalence of anti-HCV in HCC patients, as well as the same prevalence in patients with cholangiocarcinoma (CC) and combined hepatocellular-cholangiocarcinoma (combined HCC-CC), to study the clinicopathologic features of anti-HCV-positive cases. METHODS: The authors examined 141 patients with primary liver cancer who were pathologically diagnosed as having HCC (121 cases), CC (13 cases), or combined HCC-CC (7 cases). Hepatitis B surface antigen (HBsAg) and anti-HCV were measured in these patients. RESULTS: Of 121 HCC cases, 85 (70.3%) were found to be anti-HCV positive, 16 (13.2%) were HBsAg positive, and 5 (4.1%) were both anti-HCV and HBsAg positive. In 13 cases with CC and in 7 with combined HCC-CC examined, 4 (30.8%) and 5 (71.4%), respectively, were anti-HCV positive. CONCLUSIONS: The anti-HCV-positive rate was high in combined HCC-CC as well as in HCC. These three types of primary liver cancer, which were anti-HCV positive, shared two common features: male dominance and high incidences of complication with liver cirrhosis.

Adenoma, Bile Duct↗
PubMed2001

Palliative treatment in patients with unresectable hilar cholangiocarcinoma: results of endoscopic drainage in patients with type III and IV hilar cholangiocarcinoma.

OBJECTIVE: To find out how patients fared after palliative endoscopic biliary drainage for inoperable hilar cholangiocarcinoma. DESIGN: Retrospective study. SETTING: University hospital, the Netherlands. SUBJECTS: Between 1992 and 1999, 41 patients who were referred for resection had tumours that were considered unresectable after additional investigations, including an exploratory laparotomy in 16 patients. In all patients, biliary drainage was established by endoscopic retrograde cholangiography (ERCP) and insertion of endoprostheses. Twelve patients also had percutaneous transhepatic biliary drainage (PTBD). RESULTS: The patients who did not have an exploratory laparotomy had fewer complications (1/25) than those who had explorations (4/16). All patients in both groups had one or more long-term complications during follow-up, of which cholangitis, jaundice, and abdominal pain were the most often recorded. In 32 patients, endoprostheses had to be replaced, a mean of 4 times. Median survival was 9 months, with no significant difference between the groups (8 and 11 months). Adjuvant radiotherapy had no influence on survival. CONCLUSION: The patients in this series had relatively long survival times, during which they had a substantial number of complications predominantly related to biliary drainage. Because biliary-enteric bypass operations result in effective relief of symptoms and excellent palliation, we suggest that when an exploration is done for patients with type III and IV tumours, a bypass should be made.

Adult↗
PubMed2003

Thioacetamide-induced intestinal-type cholangiocarcinoma in rat: an animal model recapitulating the multi-stage progression of human cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a lethal disease, afflicting many thousands the world over. Human CCA develops through a multi-step progression model, preceded by the onset of dysplasia in the cholangiolar ductal epithelium. An animal model of multi-step carcinogenesis in the biliary tree will enable the study of genetic changes in human CCA, and provide an avenue for chemoprevention strategies. We describe an oral thioacetamide (TAA)-induced model of rat CCA that recapitulates the histologic progression of human CCA. Male Sprague-Dawley (SD) rats (n = 170), weighing 350 +/- 20 g, were used in this study. Drinking water with TAA 300 mg/l was administered orally, and the liver was harvested and examined histologically at weekly intervals, beginning at 5 weeks after initiation of TAA. Harvested tissues were formalin-fixed and paraffin embedded for morphologic and immunohistochemical studies. Multifocal bile ductular proliferation with intestinal metaplasia (presence of goblet cells) and increasing histologic atypia (biliary dysplasia) was observed by the 9th week of TAA administration. Biliary cytokeratin (CK19)-expressing invasive intestinal-type CCA with stromal desmoplasia was evident at the 16th week, and by the 22nd week, the yield rate for CCAs had increased to 100%. Invasive CCAs preceded the development of hepatic cirrhosis by at least 4 weeks; the earliest incidence of hepatic fibrosis was observed beginning at 20 weeks post-TAA administration. The progression from normal cholangioles to biliary dysplasia to invasive CCA was accompanied by up-regulation of the proto-oncogenes c-met and c-erbB-2, tyrosine kinase receptors over-expressed in human CCAs. The study was terminated at 6 months, at which time no systemic metastases or deaths were observed. Oral administration of TAA in drinking water to male SD rats provides a reproducible animal model for development of CCA with a high yield rate. In particular, the presence of biliary dysplasia beginning at the 9th week, which progresses to invasive CCA, mimics the multi-step model of human CCA. The TAA rat model may serve as a powerful pre-clinical platform for therapeutic and chemoprevention strategies for human CCA.

Animals↗
PubMed2006

Local balance of transforming growth factor-beta1 secreted from cholangiocarcinoma cells and stromal-derived factor-1 secreted from stromal fibroblasts is a factor involved in invasion of cholangiocarcinoma.

Tumor-stromal interactions are important for the progression of malignant tumors. The purpose of the present study was to examine interactions of cholangiocarcinoma (CC) cells and stromal fibroblasts with respect to stromal-derived factor-1 (SDF-1) and transforming growth factor (TGF)-beta1. Two cell lines of CC (HuCCT-1 and CCKS-1) and WI-38 fibroblast cell line were used for cell culture, and 12 CC tissue specimens for immunohistochemical studies. Invasion of CC cells was increased significantly by the supernatant from fibroblast cultures, but not by the supernatant from fibroblasts cocultured with CC cells. Expression of SDF-1 in cultured fibroblasts was downregulated by TGF-beta1 treatment, and coculture with CC cells and anti-TGF-beta1 neutralizing antibody restored the decreased SDF-1 expression, suggesting that TGF-beta1 secreted from CC cells might have reduced the expression of SDF-1 by fibroblasts and might have reduced the increased invasion of CC cells induced by the supernatant from fibroblasts. Immunohistochemical expression of TGF-beta1 in CC cells was focal or negative and that of SDF-1 was evident in stromal fibroblasts at the invasive front of CC. In conclusion, local mutual influence of TGF-beta1 secreted from carcinoma cells and SDF-1 expressed by stromal fibroblasts may be involved in invasion of CC cells.

Aged↗
PubMed1985

Are hepatolithiasis and cholangiocarcinoma aetiologically related? A morphological study of 12 cases of hepatolithiasis associated with cholangiocarcinoma.

A few cases of cholangiocarcinoma (CC) related to hepatolithiasis have been reported to date, but the aetiological relationship remains unclear. In an attempt to clarify the relationship between two phenomena, we examined morphologically 12 cases of hepatolithiasis associated with CC and 26 cases of hepatolithiasis without CC, with the aid of immunohistochemical staining for carcinoembryonic antigen (CEA). In the livers where both hepatolithiasis and CC were found, the carcinoma spread along the lumenal surface of the stone-containing bile ducts and invaded the ductal walls. Features of "chronic proliferative cholangitis" which was a basic feature of hepatolithiasis, were found within the bile duct walls where carcinoma was invading. In some cases of chronic proliferative cholangitis with hepatolithiasis in the absence of CC, atypical epithelial hyperplasia was noted. Atypical epithelial hyperplasia was also found in bile ducts adjacent to and remote from CC. Atypical epithelial hyperplasia was positive for CEA. The data lead us to speculate that chronic proliferative cholangitis in the presence of hepatolithiasis can undergo progressive changes to atypical epithelial hyperplasia which may in turn progress to CC.

Adenocarcinoma↗