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Intrahepatic Cholangiocarcinoma (intrahepatic + cholangiocarcinoma)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Oncology & Radiotherapy	42%
Hepatology	23%
Pathology	19%
Surgery & Surgical Specialties	11%

Selected Abstracts

Expression of Etk/Bmx Tyrosine Kinase in Intrahepatic Cholangiocarcinoma

JOURNAL OF SURGICAL ONCOLOGY, Issue 5 2008
Linlang Guo MD
Abstract Background Epithelial and endothelial tyrosine kinase (Etk), also known as bone marrow X kinase (Bmx) plays an important role in the growth, differentiation, apoptosis, proliferation, and tumorigenicity of epithelial cells. The purpose of this study was to investigate the expression of Etk/Bmx in intrahepatic cholangiocarcinoma (ICC) and correlated the expression with clinicopathological parameters. Methods Fifty-seven cases of ICC were immunostained for Etk/Bmx, HCV NS5, PCNA, bcl-2, and NF-,B p65. Results Etk/Bmx expression was present in 19 (33.3%) of 57 ICC specimens and correlated with cell differentiation and survival rate but not closely with tumor size and lymph node metastasis. There was a significant difference of expression of either PCNA-LI or Bcl-2 between Etk/Bmx-positive and -negative cases (P,<,0.05). However, no statistically significant association was found between Etk/Bmx expression and presence of HCV-NS5 or NF-,B p65. Conclusions Our results indicate that Etk/Bmx may be involved in the development of ICC and be a predictor of poor prognosis for ICC. HCV infection and NF-,B appears unrelated to Etk/Bmx expression. J. Surg. Oncol. 2008;97:428,432. © 2008 Wiley-Liss, Inc. [source]

Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma,

HEPATOLOGY, Issue 6 2005
Kazutaka Obama
Intrahepatic cholangiocarcinoma is a neoplasm arising in the liver, and its incidence is increasing in Japan as well as in Western countries. Prognosis of patients with this type of tumor remains unsatisfactory because no effective chemotherapeutic drugs are available, we have no sensitive tumor markers to detect this tumor in its early stage, and it is difficult to identify a high-risk group for the disease. To clarify the molecular mechanism of tumorigenesis and identify molecular targets for diagnosis and treatment, we analyzed global gene-expression profiles of 25 intrahepatic cholangiocarcinomas using tumor cell populations purified by laser microbeam microdissection and a cDNA microarray containing 27,648 genes. We identified 52 genes that were commonly upregulated and 421 that were downregulated in intrahepatic cholangiocarcinomas compared with noncancerous biliary epithelial cells. From the 52 upregulated genes, we selected P-cadherin and survivin for further investigation and corroborated enhanced expression of their products in cancer tissues by immunohistochemical staining. Furthermore, comparison between tumors with lymph node metastasis and those without metastasis identified 30 genes that were associated with lymph node involvement. In conclusion, these data should be helpful for a better understanding of the tumorigenesis of intrahepatic cholangiocarcinoma and should contribute to the development of diagnostic and therapeutic strategies for this type of tumor. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005.) [source]

Intrahepatic cholangiocarcinoma diagnosed preoperatively as hepatocellular carcinoma

JOURNAL OF SURGICAL ONCOLOGY, Issue 2 2004
Masakazu Yamamoto MD
Abstract Background Some cases of mass-forming intrahepatic cholangiocarcinoma (ICC) are diagnosed as hepatocellular carcinoma (HCC) based on preoperative imaging and clinical findings. We investigated the backgrounds of such cases. Methods Sixty-seven patients with mass-forming ICC underwent surgery from 1980 to 2002. Twenty-four of these patients received a diagnosis of HCC preoperatively. We compared the group diagnosed as HCC and that diagnosed as ICC. ICC was diagnosed histopathologically in all 67 patients. Results The specific clinical findings included high rates of associated hepatitis C virus infection, high levels of serum alpha fetoprotein, lower levels of serum CA19-9, small dimension of the tumor, hypervascular staining on angiography or computed tomography, lower rates of lymph node metastasis, and high rates of HCC occurrence in the group diagnosed as HCC. None of the patients underwent extrahepatic bile duct resection and most patients did not undergo lymph node dissection in the group diagnosed as HCC. The rates of mucus secretion and the ductal expression of mucin core protein-1 (MUC1) were significantly different between the subgroups. The cumulative survival rates were significantly better in the group diagnosed as HCC than in the group diagnosed as ICC. Conclusion Patients with ICC given a preoperative diagnosis of HCC had distinct clinical features and could be treated with the same operation as HCC patients. J. Surg. Oncol. 2004;87:80,83. © 2004 Wiley-Liss, Inc. [source]

Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma,

Pathology of peripheral intrahepatic cholangiocarcinoma with reference to tumorigenesis

HEPATOLOGY RESEARCH, Issue 4 2008
Yasuni Nakanuma
Cholangiocarcinomas (CCs) are neoplasms with cholangiocyte differentiation, and may arise from cholangiocytes of the biliary tree and possibly cholangiocyte progenitor cells. Intrahepatic CCs can be divided into the perihilar and peripheral types. Peripheral CCs present grossly as a mass forming tumor, and histologically as an adenocarcinoma of varying shapes and phenotypes. Some peripheral CCs (ductular type) are characterized by: (i) a histological resemblance to reactive bile ductules; (ii) the expression of neural cell adhesion molecule (NCAM) and vimentin. This type shows: (i) grossly, a blurred border; and (ii) histologically, carcinoma cells replacing the adjoining hepatocytes at the border of the tumor. It is frequently associated with neutrophilic infiltration and also with granulocyte and granulocyte macrophage colony-stimulating factors. We propose to call this type "ductular CC." The other peripheral CC (duct type) includes ordinary adenocarcinoma with well to moderately differentiated tubular and micropapillary patterns and is negative for NCAM but positive for mucin. This type can be called "duct CC," and shows a rather compressive growth. Interestingly, CC components of combined hepatocellular CC share the features of ductular CC, suggesting that hepatic progenitor cells may be involved in the tumorigenesis of ductular CC. The biological behavior of ductular CC and duct CC remains obscure, and follow-up and molecular studies on these tumors are required in order for these two CCs to be recognized as disease entities, and so as to evaluate their carcinogenesis. [source]

A subgroup of intrahepatic cholangiocarcinoma with an infiltrating replacement growth pattern and a resemblance to reactive proliferating bile ductules: ,bile ductular carcinoma'

HISTOPATHOLOGY, Issue 3 2007
K Kozaka
Aims:, The histogenesis and biological behaviour of peripheral intrahepatic cholangiocarcinoma (peripheral CC) remain unclarified. The aim of this study was to examine the growth pattern of peripheral CC (24 cases) in comparison with hepatocellular carcinoma (HCC, 27 cases) and metastatic colorectal adenocarcinoma (MCA, 24 cases). Methods and results:, Tumour/surrounding liver borders were classified as: (i) fibrous encapsulation, (ii) compressive growth, and (iii) infiltrating replacement. Nineteen of 24 peripheral CCs showed (iii), whereas 23 of 27 HCCs showed (i) and 17 of 24 MCAs showed (ii). In (iii), carcinoma cells infiltrated the surrounding liver without compression, and hepatic supporting vascular structures such as portal tracts were secondarily incorporated into the tumour. In (i) and (ii), the surrounding liver was compressed and no or few portal tracts were incorporated within the tumour. Fifteen of 24 peripheral CCs were composed of carcinoma cells resembling reactive bile ductules and these cells were positive for neural cell adhesion molecule (NCAM), a marker of proliferating bile ductules. The remaining nine peripheral CCs were composed of ordinary adenocarcinoma and negative for NCAM. Conclusions:, A subgroup of peripheral CCs with an infiltrating replacement growth pattern resembles reactive bile ductules and expresses NCAM. ,Bile ductular carcinoma' may be a better term for this subgroup. [source]

Surgical anatomy of the biliary tract

HPB, Issue 2 2008
DENIS CASTAING
Abstract An intimate knowledge of the morphological, functional, and real anatomy is a prerequisite for obtaining optimal results in the complex surgery of extra and intrahepatic cholangiocarcinoma. A complete presentation of the surgical anatomy of the bile ducts includes study of the liver, hepatic surface, margins, and scissures. The frequent variations from the normal anatomy are described and an overview of the blood supply and lymphatics of the biliary tract is presented. [source]

Infrequent microsatellite instability in liver fluke infection-associated intrahepatic cholangiocarcinomas from Thailand

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2003
Upama Liengswangwong
Abstract The liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) is a major liver cancer in Northeast Thailand. The molecular basis of this ICC is poorly understood. To address possible roles of the DNA mismatch repair (MMR) system in ICC carcinogenesis, a fluorescence-labeling PCR/laser scanning technique with high sensitivity was employed to analyze genomic instability in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in 24 fresh and 13 formalin-fixed, paraffin-embedded tissues of ICC and their corresponding normal parts. Microsatellite instability (MSI) was assessed in nDNA, using 12 highly polymorphic loci including 5 Bethesda markers. These loci were mainly related to major MMR genes, hMSH2 and hMLH1. Also 3 (C)n and/or (C)n(A)n repeat instability at 1 noncoding region in the displacement-loop (D-loop) and 2 coding sequences in NADH dehydrogenase subunit 1 and subunit 5 gene in mtDNA were analyzed. MSI was only detected in 1 (2.7%), 6 (16.7%), 1 (2.9%), 1 (2.9%) or 2 (6.3%) out of 37, 36, 35, 35 or 32 cases at BAT-25, D2S123, D3S1611, D11S904 or D17S250, respectively. LOH was found at D3S1298, D3S1561, D5S346 and TP53 in 4 (18.2%) out of 22, 2 (18.2%) out of 11, 6 (33.3%) out of 18 and 3 (12.5%) out of 24 informative cases, respectively. In mtDNA, none except a single case out of the 37 (2.7%) exhibited repeat sequence instability in the D-loop. We conclude that the liver fluke infection-associated ICC in Thailand is classified as low frequency MSI or microsatellite stable type and that DNA MMR system, through hMSH2 and hMLH1 gene mutations, does not play a major role in its carcinogenesis. © 2003 Wiley-Liss, Inc. [source]

Expression of Etk/Bmx Tyrosine Kinase in Intrahepatic Cholangiocarcinoma

Complex liver resection for a large intrahepatic cholangiocarcinoma in a Jehovah's witness: A strategy to avoid transfusion

JOURNAL OF SURGICAL ONCOLOGY, Issue 3 2007
FRCS, Omar Barakat MD
Abstract Although morbidity and mortality after liver resection have improved over the last two decades, complex liver resections still require perioperative blood transfusions. In this report, we describe the use of a combined left trisegmentectomy and caudate lobectomy, along with resection of the inferior vena cava, to treat a large intrahepatic cholangiocarcinoma in a Jehovah's Witness. To our knowledge, this is the first report of major liver resection for a large malignant tumor in this patient population. We also discuss the perioperative strategy and surgical technique we used to minimize blood loss and avoid transfusion. This approach could be a safe alternative for use in all patients with complex liver tumor, regardless of their religious beliefs, to reduce the risks and cost associated with blood transfusion. J. Surg. Oncol. 2007;96: 249,253. © 2007 Wiley-Liss, Inc. [source]

Expression of DPC4/Smad4 gene in stone-containing intrahepatic bile duct

JOURNAL OF SURGICAL ONCOLOGY, Issue 4 2006
King-Teh Lee MD
Abstract Background and Objectives Hepatolithiasis is etiologically related to cholangiocarcinoma. We underwent this study with an attempt to examine the expression of DPC4/Smad4 gene in stone-containing intrahepatic bile ducts (IHD) and intrahepatic cholangiocarcinoma (ICC). Patients and Methods The immunohistochemical method and RT-PCR analysis were used to study the expression of DPC4/Smad4 gene in normal IHD, stone-containing IHD, and ICC. All the specimens were from hepatic resection. Results The immunohistochemical study showed that all specimens from 24 normal IHD had marked expression of DPC4/Smad4 gene, while there was 4.4% (2/46) and 33.3% (3/9) loss of DPC4/Smad4 expression in stone-containing IHD and ICC, respectively. Among the specimens of stone-containing IHD, all the hyperplastic epithelial cells showed normal expression of DPC4/Smad4 gene while dysplastic epithelial cells showed 20% (2/10) loss expression of DPC4/Smad4. The RT-PCR analysis showed that the normal IHD had the highest content of DPC4/Smad4 mRNA, which was threefold and sixfold higher than that of stone-containing IHD and ICC, respectively. Conclusion Loss expression of DPC4/Smad4 gene was found both in stone-containing IHD and ICC. Dysplastic epithelium of stone-containing IHD had higher potential for malignant transformation. J. Surg. Oncol. 2006;94:338,343. © 2006 Wiley-Liss, Inc. [source]

Intrahepatic cholangiocarcinoma diagnosed preoperatively as hepatocellular carcinoma

The clinical presentation and prognostic factors for intrahepatic and extrahepatic cholangiocarcinoma in a tertiary care centre

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010
A. G. SINGAL
Aliment Pharmacol Ther,31, 625,633 Summary Background, The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined. Aim, To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients. Methods, Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed. Results, In all, 136 patients had cholangiocarcinoma (79 intra- and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months,25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01,1.07), CA 19-9 levels >100 U/mL (HR 1.90, 95%CI 1.17,3.08) and stage of disease (HR 1.51, 95%CI 1.16,1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26,0.88). There were no significant differences regarding clinical presentation, disease stage (P = 0.98), and survival (P = 0.51) between intra- and extrahepatic cholangiocarcinoma. Conclusions, Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra- and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19-9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables. [source]

Staging for intrahepatic cholangiocarcinoma

LIVER INTERNATIONAL, Issue 7 2010
Norihiro Kokudo
No abstract is available for this article. [source]

Lymphoepithelioma-like cholangiocarcinoma not associated with EBV

PATHOLOGY INTERNATIONAL, Issue 1 2008
Shiro Adachi
Reported herein is an unusual case of intrahepatic cholangiocarcinoma with lymphoepithelioma-like appearance in a 64-year-old man who was found to have an intrahepatic mass without cirrhosis. The tumor had two distinct histological patterns with dense lymphoplasmacytic infiltrate. The first was similar to nasopharyngeal undifferentiated carcinoma; the second pattern was a well-differentiated adenocarcinoma. Transition between the two components was observed in the same duct. Immunohistochemistry indicated that the tumor was immunoreactive with AE1/AE3 and cytokeratin (CK) 7, but negative for CEA and CK20. Stromal inflammatory infiltrate primarily consisted of plasma cells and lymphocytes. Immunohistochemical examination and in situ hybridization for EBV showed no integration of the virus in the tumor cells. Intrahepatic lymphoepithelioma-like carcinoma is rare, and most are associated with EBV. Only three cases were not associated with EBV. The authors would like to add one more example of the tumors not associated with EBV. [source]

Combined hepatocellular carcinoma and cholangiocarcinoma with components of mucinous carcinoma arising in a cirrhotic liver

PATHOLOGY INTERNATIONAL, Issue 4 2006
Daisaku Morita
A rare autopsy case of combined hepatocellular and cholangiocarcinoma, occurring in a 54-year-old man with liver cirrhosis, is presented. Initial laboratory data included CEA 52.1 ng/mL, DUPAN-2 1600 U/mL, AFP 2 ng/mL, and negativity for hepatitis B surface antigen, hepatitis B early antigen and hepatitis B core antibody. Ultrasonography and CT scan showed a large tumor node in the liver with ringed enhancement, swelling of several para-aortic lymph nodes, and ascites. Clinically, it was not possible to determine whether the hepatic tumor was an intrahepatic cholangiocarcinoma or a metastatic carcinoma. Histologically, the primary lesion was composed solely of hepatocellular carcinoma (HCC) with a trabecular pattern, and the intrahepatic metastases consisted of a variable admixture of HCC and cholangiocarcinoma (CC) with excessive mucin production. Interestingly, the tumor cell cluster showing a trabecular growth pattern produced mucin and had immunohistochemical expression of hepatocyte, cytokeratins 7 and 8. It is concluded that these hepatic tumor cells had both HCC and CC characters. [source]

Over-expression of polycomb group protein EZH2 relates to decreased expression of p16INK4a in cholangiocarcinogenesis in hepatolithiasis,

THE JOURNAL OF PATHOLOGY, Issue 2 2008
M Sasaki
Abstract Polycomb group protein EZH2 and Bmi1 are reportedly involved in the progression of malignant tumours. We examined the participation of EZH2 in multi-step cholangiocarcinogenesis in hepatolithiasis with respect to tumour suppressor gene p16INK4a. We examined 20 hepatolithiatic livers with intrahepatic cholangiocarcinoma (ICC) and 10 histologically normal livers. Neoplastic biliary lesions were classified into biliary intraepithelial neoplasm (BilIN-1, 2 and 3) and invasive carcinoma. We selected 15 foci of invasive carcinoma, 8 BilIN-3 (carcinoma in situ), 12 BilIN-2 (high-grade dysplasia), 32 BilIN-1 (low-grade dysplasia) and 37 non-neoplastic biliary epithelia from these livers. Expression of p16INK4a, EZH2 and Bmi1 were surveyed in these foci. P16INK4a promoter methylation was examined in microdissected tissues. Taking advantage of two cell lines of CC (HuCTT-1 and TFK-1) and small interfering RNA (siRNA), the effects of the knockdown of EZH2 on p16INK4a methylation of CC cells were examined. Expression of p16INK4a, which was frequent in BilIN1, was decreased in BilIN-2/3 and invasive carcinoma, while EZH2 expression showed step-wise increase from BilIN-1, -2 and -3 to invasive carcinoma (p < 0.01). P16INK4a promoter hypermethylation was related to aberrant expression of EZH2. The knockdown of EZH2 in cultured CC cells decreased p16INK4a methylation and decreased binding of EZH2 to the p16INK4a gene promoter. The latter suggested that direct binding of EZH2 is involved in the regulation of the p16INK4a gene. Our data suggest that over-expression of EZH2 may induce hypermethylation of p16INK4a promoter followed by decreased expression of p16INK4a in the multi-step cholangiocarcinogenesis through intraepithelial neoplasm in hepatolithiasis. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

An intraductal papillary component is associated with prolonged survival after hepatic resection for intrahepatic cholangiocarcinoma,

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2004
Y. Tajima
Background: The outcome after surgery for intrahepatic cholangiocarcinoma (ICC) is dismal and data on long-term survival are not available. This study evaluated prognostic indicators and characteristic features of long-term survivors after hepatic resection for ICC. Methods: Thirty-one patients who had undergone hepatic resection for ICC were studied. Univariate and multivariate survival analyses of clinicopathological data included an intraductal papillary carcinoma component (IDPCC) in the tumour, which was defined as the histological demonstration of cancer cells growing in a papillary fashion into the lumen of the large bile duct. Results: The overall cumulative survival rate after hepatic resection for ICC was 51·2 per cent at 1 year and 24·5 per cent at 5 years, with a mean(s.d.) survival time of 11(4) months. The presence of IDPCC (P = 0·003), curative resection (P = 0·009) and the absence of perineural invasion (P = 0·040) were identified as favourable independent prognostic factors in multivariate analysis. Eight patients with IDPCC had a 5-year survival rate of 87·5 per cent and a mean(s.d.) survival time of 69(13) months. All seven patients who survived for more than 5 years after surgery had IDPCC, regardless of the gross appearance of the tumour. Conclusion: An IDPCC in the tumour resulted in long-term survival after hepatic resection for ICC. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma

CANCER SCIENCE, Issue 7 2004
Satoshi Yamamoto
Although hepatitis C virus (HCV)-related cirrhosis has been suggested as a risk factor for intrahepatic cholangiocarcinoma (ICC), few sizeable studies have tested this hypothesis. We investigated ICC risk factors, with special reference to HCV infection. We conducted a hospital-based case-control study including 50 ICC patients and 205 other surgical patients without primary liver cancer. HCV seropositivity was detected in 36% of ICC patients and 3% of controls. By univariate analysis, the odds ratio (OR) for association of anti-HCV antibodies with development was 16.87 (95% confidence interval (CI), 5.69 to 50.00). History of blood transfusion or diabetes mellitus, elevated serum total bilirubin, elevated aspartate aminotransferase and alanine aminotrans-ferase, decreased serum albumin and decreased platelet count were identified as other possible ICC risk factors. By multivariate analysis, anti-HCV antibodies (adjusted OR, 6.02; 95% Cl, 1.51 to 24.1), elevated alanine aminotransferase, decreased serum albumin, and decreased platelet count were found to be independent risk factors for ICC development. As liver status worsened, the adjusted OR for ICC tended to increase. HCV infection is a likely etiology of ICC in Japan. [source]