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Cholangiocarcinoma
Kinds of Cholangiocarcinoma Terms modified by Cholangiocarcinoma Selected AbstractsCholangiocarcinoma in primary sclerosing cholangitis is associated with NKG2D polymorphisms,HEPATOLOGY, Issue 1 2008Espen Melum Primary sclerosing cholangitis (PSC) is often complicated by the development of cholangiocarcinoma (CCA). Genetic variation of natural killer cell receptor G2D (NKG2D) has been associated with cancer susceptibility. An important ligand for NKG2D, major histocompatibility complex class I chain-related molecule A (MICA), serves as a marker of cellular stress. The 5.1 allele of the gene encoding MICA has been associated with PSC. In this study, we aimed to investigate the influence of genetic variations in the NKG2D-MICA receptor-ligand pair on the risk of CCA in patients with PSC. Seven single nucleotide polymorphisms (SNPs) covering the NKG2D gene were genotyped in 365 Scandinavian PSC patients and 368 healthy controls with TaqMan technology. Genotype data on the MICA 5.1 variant were available from previous studies. Forty-nine of the PSC patients (13.6%) had developed CCA at the time of study. Two of the NKG2D SNPs were associated with an increased risk of CCA: rs11053781 [odds ratio (OR) = 2.08, 95% confidence interval (CI) = 1.31-3.29, corrected P (Pc) = 0.011] and rs2617167 (OR = 2.32, 95% CI = 1.47-3.66, Pc = 0.0020). Carriership of the MICA 5.1 allele was associated with resistance against CCA (OR = 0.43, 95% CI = 0.20-0.95, not corrected P = 0.032). Conclusion: Our results show that genetic variants of the NKG2D receptor are associated with development of CCA in PSC patients. This suggests that interaction between NKG2D and MICA is involved in protection against CCA in PSC. Patients who are homozygous for the nonrisk alleles are unlikely to develop CCA; this finding could be helpful in identifying PSC patients with a low CCA risk. (HEPATOLOGY 2007.) [source] Cholangiocarcinoma in primary sclerosing cholangitis: Who is at risk and how do we screen?HEPATOLOGY, Issue 1 2000Piet C. de Groen M.D. No abstract is available for this article. [source] Epidemiology, risk factors, and pathogenesis of cholangiocarcinomaHPB, Issue 2 2008S. A. KHAN Abstract Cholangiocarcinoma (CCA) is a fatal cancer of the biliary epithelium, arising either within the liver (intrahepatic, ICC) or in the extrahepatic bile ducts (extrahepatic ECC). Globally, CCA is the second most common primary hepatic malignancy. Several recent epidemiological studies have shown that the incidence and mortality rates of ICC are increasing. This review of the literature on the international epidemiological rates of CCA, both intra- and extrahepatic, explores possible explanations for the trends found. The possible role of epidemiological artifact in the findings is discussed and the known risk factors for CCA are summarized. These include primary sclerosing cholangitis, liver fluke infestation, congenital fibropolycystic liver, bile duct adenomas, and biliary papillomatosis, hepatolithiasis, chemical carcinogens such as nitrosamines, Thorotrast, chronic viral hepatitis, cirrhosis, chronic non-alcoholic liver disease and obesity. Potential pathways involved in the molecular pathogenesis of CCA are also summarized. [source] Cholangiocarcinoma: preoperative biliary drainage (Con)HPB, Issue 2 2008A. LAURENT Aim. In patients with malignant hilar obstruction, liver resection is associated with an increased risk of postoperative liver failure attributed to the need for major liver resection in a context of obstructive jaundice. To overcome this issue, most authors recommend preoperative biliary drainage (PBD). However, PBD carries risks of its own, including, primarily, sepsis and, more rarely, tumor seeding, bile peritonitis, and hemobilia. We, unlike most authors, have not used routine PBD before liver resection in jaundiced patients. Material and methods. Our series includes 62 patients who underwent major liver resection for cholangiocarcinoma; 33 of these had elevated bilurubin (60,470 µmol/l) and were operated without PBD. There were 43 extended right hepatectomies and 18 extended left hepatectomies. Results. Hospital deaths occurred in 5 patients (8%) including 3 of 33 jaundiced patients (9%, ns). All deaths occurred after extended right hepatectomy (12%), including 3 patients with a serum bilirubin level above 300 µmol/l and 2 with normal bilirubin. There were no deaths after left-sided resections, whatever the level of bilirubin. Conclusions. PBD can be omitted in the following situations: recent onset jaundice (<2,3 weeks), total bilirubin <200 µmol/l, no previous endoscopic or transhepatic cholangiography, absence of sepsis, future liver remnant >40%. These criteria include most patients requiring left-sided resections and selected patients requiring right-sided resections. In other cases, PBD is required, associated with portal vein embolization in the event of a small future liver remnant. [source] Enhanced expression of mucin 6 glycoprotein in cholangiocarcinoma tissue from patients in Thailand as a prognostic marker for survivalJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2008Peti Thuwajit Abstract Background and Aim:, Cholangiocarcinoma (CCA) is a mucin-producing cancer that has poor prognosis. Mucin 6 (MUC6) is a mucin that is normally co-expressed with the trefoil factor family-2 (TFF2) trefoil peptide. Both MUC6 and TFF2 have been reported to be involved in the progression of many types of cancers. The aim of this study was to determine the expression of MUC6 and TFF2 in CCA tissues and associate these results with clinical data. Methods:, MUC6 and TFF2 were detected in CCA tissues by immunohistochemistry. The correlations of MUC6 and TFF2 expressions with clinical data were analyzed. Results:, We determined the significant co-expression of both proteins in serial CCA tissues. The high expressions of MUC6 and TFF2 were demonstrated in 37% and 31% of patients, respectively. The expression levels decreased in the advanced stage of CCA when clinical metastasis was exhibited. The high expression of either protein showed a correlation with prolonged postoperative survival time, but only a high expression of MUC6 is significantly correlated with a 5-year survival rate. A multivariate Cox regression analysis revealed that a low expression of MUC6, high expression of TFF2, age of patients >56 years, tumor size >5 cm, and poorly-differentiated histological type were independent, poor prognostic indicators for CCA. Conclusion:, MUC6 showed a good correlation with the survival of CCA patients. It may be of value to propose that MUC6 is a good prognostic marker for CCA management. [source] Hepatobiliary and pancreatic: Cholangiocarcinoma in a double bile ductJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2006T Yamamoto [source] Genetic Hemochromatosis With Normal Transferrin Saturation In A Man With Cholangiocarcinoma And Yellow Nail SyndromeJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2003Fabio Di Stefano No abstract is available for this article. [source] Expression of Etk/Bmx Tyrosine Kinase in Intrahepatic CholangiocarcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2008Linlang 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] Liver transplantation for primary sclerosing cholangitisLIVER INTERNATIONAL, Issue 2 2000Paul J. Gow Abstract: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology that is progressive in most symptomatic patients, advancing toward cirrhosis and liver failure. Liver transplantation is the only therapeutic option for patients with end stage liver disease resulting from this disorder. The results of transplantation for PSC are excellent with one-year survival rates of 90,97% and five-year survival rates of 80,85%, but are closely related to pre-transplant Child-Pugh stage. Recurrence of PSC after liver transplantation is common, occurring in up to 20% of patients, but it appears to have little effect on patient survival, as survival of patients with recurrent PSC is similar to that of those without evidence of recurrence. Cholangiocarcinoma is a catastrophic complication of PSC and as yet no reliable screening method exists. The results of liver transplantation for patients with clinically apparent cholangiocarcinoma are extremely poor, however in patients in whom a microscopic tumour is detected in the explanted liver, survival is similar to those transplanted with PSC without cholangiocarcinoma. Activity of inflammatory bowel disease (IBD) appears to be more severe after transplantation, especially in units where steroid immunosuppression is withdrawn early. Colon cancer appears within the first few years after transplantation in approximately 7% of patients with IBD who are transplanted for PSC. Annual colonoscopy in this population seems prudent. [source] Liver transplantation for incidental cholangiocarcinoma: Analysis of the Canadian experienceLIVER TRANSPLANTATION, Issue 11 2005Peter Ghali Cholangiocarcinoma is a biliary tumor, which not infrequently complicates primary sclerosing cholangitis. It carries a poor prognosis and, with the exception of carefully selected individuals in research protocols, contraindicates orthotopic liver transplantation. There has been some suggestion that cholangiocarcinomas incidentally discovered at the time of transplantation carry a better prognosis. The goal of this retrospective study was to perform a national review of outcomes after liver transplantation in Canadian recipients found to have incidental cholangiocarcinoma in their explanted native liver. Six of the seven liver transplant centers in Canada provided clinical and follow-up information on all liver transplant recipients found to have incidental cholangiocarcinoma in their explants. The diagnosis or suspicion of cholangiocarcinoma prior to transplantation were exclusion criteria for this study. Ten individuals with cholangiocarcinoma were transplanted between 1996 and 2003. The median duration of follow-up was 28 months. Eight of the 10 had PSC. All of the tumors were stage I or II. The 3-year survival for these patients was 30%. The median time to recurrence was 26 months (95% confidence interval 13uu-uu37), and the median time to death was 30 months (95% confidence interval 28uu-uu53). In conclusion, although early survival of patients transplanted for incidental cholangiocarcinoma appears good, intermediate- and long-term survival rates are not better than for individuals historically transplanted with known cholangiocarcinoma. Aggressive investigation for cholangiocarcinoma is mandated. Incidentally found tumours remain a difficult treatment problem, and prospective adjuvant chemo-, radio-, and immunotherapies should be investigated. (Liver Transpl 2005;11:1412,1416.) [source] Recurrence-Free Long-Term Survival After Liver Transplantation in Patients with 18F-FDG Non-Avid Hilar Cholangiocarcinoma on PETAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009A. Kornberg The aim of this retrospective study was to assess the value of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for predicting biological tumor behavior and outcome after liver transplantation (LT) in patients with otherwise unresectable hilar cholangiocarcinoma (HC). Preoperative 18F-FDG-PET scanning was performed in 13 patients with type IV Klatskin tumor before LT. PET+ status indicated patients with an increased pretransplant 18F-FDG uptake, whereas PET, recipients had no increased preoperative 18F-FDG uptake on PET. Pretransplant PET findings were correlated with histopathological tumor characteristics and patient outcome after LT. Eight patients demonstrated positive preoperative PET findings (61.5%), whereas five patients had no increased preoperative 18F-FDG tumor uptake (38.5%) on PET. One PET+ patient died after 1 month due to liver allograft dysfunction. Seven PET+ liver recipients developed tumor recurrence, whereas five PET, patients were tumor-free alive after a median of 76 months post-LT (p = 0.001). The 2-year recurrence-free survival rate after LT was 100% in PET, patients and 28.6% in the PET+ population (log-rank = 0.008). Our results suggest that patients with 18F-FDG non-avid HC on PET may achieve recurrence-free long-term survival after LT. [source] Epidemiology of cholangiocarcinoma: An update focusing on risk factorsCANCER SCIENCE, Issue 3 2010Hai-Rim Shin (Cancer Sci 2010; 101: 579,585) Cholangiocarcinoma is relatively rare, but high incidence rates have been reported in Eastern Asia, especially in Thailand. The etiology of this cancer of the bile ducts appears to be mostly due to specific infectious agents. In 2009, infections with the liver flukes, Clonorchis sinensis or Opistorchis viverrini, were both classified as carcinogenic to humans by the International Agency for Research on Cancer for cholangiocarcinoma. In addition, a possible association between chronic infection with hepatitis B and C viruses and cholangiocarcinoma was also noted. The meta-analysis of published literature revealed the summary relative risks of infection with liver fluke (both Opistorchis viverrini and Clonorchis sinensis), hepatitis B virus, and hepatitis C virus to be 4.8 (95% confidence interval [95% CI]: 2.8,8.4), 2.6 (95% CI: 1.5,4.6), and 1.8 (95% CI: 1.4,2.4), respectively , liver fluke infection being the strongest risk factor for cholangiocarcinoma. Countries where human liver fluke infection is endemic include China, Korea, Vietnam, Laos, and Cambodia. The number of infected persons with Clonorchis sinensis in China has been estimated at 12.5 million with considerable variations among different regions. A significant regional variation in Opistorchis viverrini prevalence was also noted in Thailand (average 9.6% or 6 million people). The implementation of a more intensive preventive and therapeutic program for liver fluke infection may reduce incidence rates of cholangiocarcinoma in endemic areas. Recently, advances have been made in the diagnosis and management of cholangiocarcinoma. Although progress on cholangiocarcinoma prevention and treatment has been steady, more studies related to classification and risk factors will be helpful to develop an advanced strategy to cure and prevent cholangiocarcinoma. [source] Pathology of peripheral intrahepatic cholangiocarcinoma with reference to tumorigenesisHEPATOLOGY RESEARCH, Issue 4 2008Yasuni 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] Review article: the modern diagnosis and therapy of cholangiocarcinomaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2006H. MALHI Summary Cholangiocarcinomas are epithelial neoplasms that originate from cholangiocytes and can occur at any level of the biliary tree. They are broadly classified into intrahepatic tumours, (extrahepatic) hilar tumours and (extrahepatic) distal bile duct tumours. In spite of well-understood predispositions, most cholangiocarcinomas arise in the absence of risk factors. In suspected cases, the diagnosis can be established with non-invasive imaging studies. Biliary invasion should be reserved for patients with obstruction. In high-risk patients, advanced cytological tests of aneuploidy (digital image analysis and fluorescent in situ hybridization) aid early diagnosis. In the absence of primary sclerosing cholangitis, curative surgical resection has 5-year survival rates of 2,43%, higher survival observed in patients with clear surgical margins and concomitant hepatic resection for hilar tumours. Patients with unresectable cholangiocarcinoma or pre-existing primary sclerosing cholangitis should be considered for liver transplantation with neoadjuvant chemoirradiation, in specialized centres. [source] Primary sclerosing cholangitis as a cause of false positive bile duct brushing cytology: Report of two cases.DIAGNOSTIC CYTOPATHOLOGY, Issue 2 2005Lester J. Layfield M.D. Abstract Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology characterized by ongoing inflammation, destruction, and fibrosis of intrahepatic and extrahepatic bile ducts. Irregular narrowing and dilation of the biliary duct system produces the characteristic beaded pattern seen on cholangiogram. Malignant degeneration resulting in cholangiocarcinoma is a well-recognized sequela of PSC. Bile duct brushing cytology is the primary screening technique for cholangiocarcinoma. It is associated with a relatively low sensitivity but high specificity. Few false positive bile duct brushings have been reported in the literature, with the majority of these having occurred in a background of PSC. We report two patients with PSC in whom bile duct brush cytologies were falsely positive for carcinoma. Diagn. Cytopathol. 2005;32:119,124. © 2005 Wiley-Liss, Inc. [source] Mirizzi syndrome Type IV: A rare entityDIGESTIVE ENDOSCOPY, Issue 4 2003Everson Luiz De Almeida Artifon Mirizzi's syndrome, characterized by obstructive jaundice due to an extrinsic compression of common hepatic duct by an impacted gallstone in the cystic duct or the neck of the gallbladder, is a rare complication of gallstone disease. The present case describes Mirizzi's syndrome classified as Type IV in a 50-year-old man with obstructive jaundice. Abdominal computed tomography scan demonstrated a dilated intrahepatic biliary tree and a tumoral mass at the porta hepatis, suggesting cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography also suggested cholangiocarcinoma involving the entire circumference of the common hepatic duct in porta hepatis. The diagnosis of Mirizzi's syndrome Type IV was confirmed during cholecystectomy, withdrawal of gallstone and Roux-en-Y hepaticojejunostomy. [source] Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis,HEPATOLOGY, Issue 1 2010Sanjay Y. Bangarulingam Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Fluorescence in situ hybridization (FISH) is a cytological test designed to enhance early CCA diagnosis. The long-term outcome of PSC patients with a positive FISH test (polysomy, trisomy/tetrasomy) are unclear. All PSC patients with at least one FISH test were identified and defined to have CCA if they had a positive tissue biopsy, positive cytology, or evidence of cancer in the explant after liver transplantation. A total of 235 PSC patients had at least one FISH test performed, and 56 patients had CCA on histopathology (n = 35) or cytology (n = 21). Overall, 120 of 235 (51%) of PSC patients tested for FISH were positive, but only one third of these positive patients had CCA. Sensitivity and specificity for FISH polysomy were 46% and 88%, and for trisomy/tetrasomy they were 25% and 67%, respectively. Survival analysis showed that patients with FISH polysomy had an outcome similar to patients with CCA; whereas FISH trisomy/tetrasomy patients had an outcome similar to patients with negative FISH tests. The FISH polysomy patients without cancer compared with those with CCA had lower serum bilirubin, lower carbohydrate antigen 19-9 (CA 19-9), lower Mayo risk score, and lower occurrence of dominant strictures. Conclusion: In PSC patients, the presence of a dominant stricture plus FISH polysomy has a specificity of 88% for CCA. Patients with FISH showing trisomy or tetrasomy have a similar outcome to patients with negative FISH. FISH testing should be used selectively in patients with other signs indicating CCA and not as a screening tool in all PSC patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). (HEPATOLOGY 2009.) [source] Cholangiocarcinoma in primary sclerosing cholangitis is associated with NKG2D polymorphisms,HEPATOLOGY, Issue 1 2008Espen Melum Primary sclerosing cholangitis (PSC) is often complicated by the development of cholangiocarcinoma (CCA). Genetic variation of natural killer cell receptor G2D (NKG2D) has been associated with cancer susceptibility. An important ligand for NKG2D, major histocompatibility complex class I chain-related molecule A (MICA), serves as a marker of cellular stress. The 5.1 allele of the gene encoding MICA has been associated with PSC. In this study, we aimed to investigate the influence of genetic variations in the NKG2D-MICA receptor-ligand pair on the risk of CCA in patients with PSC. Seven single nucleotide polymorphisms (SNPs) covering the NKG2D gene were genotyped in 365 Scandinavian PSC patients and 368 healthy controls with TaqMan technology. Genotype data on the MICA 5.1 variant were available from previous studies. Forty-nine of the PSC patients (13.6%) had developed CCA at the time of study. Two of the NKG2D SNPs were associated with an increased risk of CCA: rs11053781 [odds ratio (OR) = 2.08, 95% confidence interval (CI) = 1.31-3.29, corrected P (Pc) = 0.011] and rs2617167 (OR = 2.32, 95% CI = 1.47-3.66, Pc = 0.0020). Carriership of the MICA 5.1 allele was associated with resistance against CCA (OR = 0.43, 95% CI = 0.20-0.95, not corrected P = 0.032). Conclusion: Our results show that genetic variants of the NKG2D receptor are associated with development of CCA in PSC patients. This suggests that interaction between NKG2D and MICA is involved in protection against CCA in PSC. Patients who are homozygous for the nonrisk alleles are unlikely to develop CCA; this finding could be helpful in identifying PSC patients with a low CCA risk. (HEPATOLOGY 2007.) [source] Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma,HEPATOLOGY, Issue 1 2008Alejandro Forner This study prospectively evaluates the accuracy of contrast-enhanced ultrasound (CEUS) and dynamic magnetic resonance imaging (MRI) for the diagnosis of nodules 20 mm or smaller detected during ultrasound (US) surveillance. We included 89 patients with cirrhosis [median age, 65 years; male 53, hepatitis C virus 68, Child-Pugh A 80] without prior hepatocellular carcinoma (HCC) in whom US detected a small solitary nodule (mean diameter, 14 mm). Hepatic MRI, CEUS, and fine-needle biopsy (gold standard) (FNB) were performed at baseline. Non-HCC cases were followed (median 23 months) by CEUS/3 months and MRI/6 months. FNB was repeated up to 3 times and on detection of change in aspect/size. Intense arterial contrast uptake followed by washout in the delayed/venous phase was registered as conclusive for HCC. Final diagnoses were: HCC (n = 60), cholangiocarcinoma (n = 1), and benign lesions (regenerative/dysplastic nodule, hemangioma, focal nodular hyperplasia) (n = 28). Sex, cirrhosis cause, liver function, and alpha-fetoprotein (AFP) levels were similar between HCC and non-HCC groups. HCC patients were older and their nodules significantly larger (P < 0.0001). First biopsy was positive in 42 of 60 HCC patients. Sensitivity, specificity, and positive and negative predictive values of conclusive profile were 61.7%, 96.6%, 97.4%, and 54.9%, for MRI, 51.7%, 93.1%, 93.9%, and 50.9%, for CEUS. Values for coincidental conclusive findings in both techniques were 33.3%, 100%, 100%, and 42%. Thus, diagnosis of HCC 20 mm or smaller can be established without a positive biopsy if both CEUS and MRI are conclusive. However, sensitivity of these noninvasive criteria is 33% and, as occurs with biopsy, absence of a conclusive pattern does not rule out malignancy. These results validate the American Association for the Study of Liver Disease (AASLD) guidelines. (HEPATOLOGY 2007.) [source] Genome-wide analysis of gene expression in human intrahepatic cholangiocarcinoma,HEPATOLOGY, Issue 6 2005Kazutaka 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] Unique epithelial cell production of hepatocyte growth factor/scatter factor by putative precancerous intestinal metaplasias and associated "intestinal-type" biliary cancer chemically induced in rat liverHEPATOLOGY, Issue 6 2000Guan-Hua Lai Recently, we observed that Met, the receptor for hepatocyte growth factor/scatter factor (HGF/SF), is overexpressed in epithelial cells of both early-appearing intestinal metaplastic glands in precancerous hepatic cholangiofibrotic tissue and neoplastic glands in later developed intestinal-type of cholangiocarcinoma originated from the furan rat model of cholangiocarcinogenesis when compared with normal and hyperplastic intrahepatic biliary epithelia. We now show that HGF/SF is also aberrantly expressed in a manner closely paralleling that of its receptor in the neoplastic epithelial cells of furan-induced rat cholangiocarcinomas and in a majority of metaplastic epithelial cells within earlier formed precancerous hepatic cholangiofibrotic tissue. Using in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR), we further showed specific expression of HGF/SF messenger RNA (mRNA) in a novel rat cholangiocarcinoma epithelial cell line overexpressing Met. This cholangiocarcinoma cell line, termed C611B, was established from tumorigenic cells isolated from a furan-induced transplantable tumor. Moreover, we detected by in situ hybridization strong expression of HGF/SF mRNA transcripts in the cancerous epithelial glands of cholangiocarcinoma developed in recipient rats after in vivo cell transplantation of C611B cells. In contrast, mRNA transcripts and protein immunoreactivity for this cytokine were not detected in hepatocytes and biliary epithelial cells in adult normal rat liver nor in rat hyperplastic intrahepatic biliary epithelium. Our results clearly show that HGF/SF becomes aberrantly expressed in cholangiocarcinoma epithelium and in putative precancerous intestinal metaplastic epithelium induced in the liver of furan-treated rats. [source] Pathology of peripheral intrahepatic cholangiocarcinoma with reference to tumorigenesisHEPATOLOGY RESEARCH, Issue 4 2008Yasuni 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] Hepatitis C virus and malignancyHEPATOLOGY RESEARCH, Issue 6 2007Arief Suriawinata Hepatitis C virus (HCV) is a hepatotropic virus that causes chronic hepatitis, fibrosis and cirrhosis. HCV is associated with the development of primary liver tumors, namely hepatocellular carcinoma, cholangiocarcinoma and lymphoma. This article reviews HCV-related malignancies, and their prevalence and probable oncogenesis. [source] Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidenceHISTOPATHOLOGY, Issue 2 2008F Zhang Aims:, Combined hepatocellular cholangiocarcinoma (CHC) is a rare form of primary liver cancer, showing a mixture of hepatocellular and biliary features. Data suggest that most CHC arise from hepatic progenitor cells (HPCs). The aim was to investigate the origin of CHC. Methods and results:, Twelve cases of CHC were studied by immunohistochemistry for hepatocytic (hepPar1, ,-fetoprotein), cholangiocytic cytokeratin [(CK) 7, CK19], hepatic progenitor cell (OV-6), haematopoietic stem cell (c-kit, CD34), as well as CD45 and chromogranin-A markers. The combination of double-fluorescence immunostaining consisted of HepPar1 with CK19, and c-kit with OV-6. All 12 cases demonstrated more or less transitional areas, with strands/trabeculae of small, uniform, oval-shaped cells including scant cytoplasm and hyperchromatic nuclei embedded within a thick, desmoplastic stroma; however, two cases were found to consist entirely of such transitional areas. Simultaneous co-expression of hepPar1 and CK7, or CK19, was demonstrated in 10/12 (83.3%) cases of CHC. c-kit expression was noted in 10/12 (83.3%) cases, of which 7/10 (70%) showed co-expression of OV-6. Conclusions:, The results suggest that CHC are of HPC origin, supporting the concept that human hepatocarcinogenesis may originate from the transformation of HPCs. [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 2007K 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] Resection of hilar cholangiocarcinoma with left hepatectomy after pre-operative embolization of the proper hepatic arteryHPB, Issue 2 2010Yoshikazu Yasuda Abstract Background:, Right or right-extended hepatectomy including the caudate lobe is the most common treatment for hilar cholangiocarcinoma (HC). A 5-year survival of up to 60% can be achieved using this procedure if R0-resection is obtained. However, for some patients a left-sided liver resection is necessary to obtain radical resection. The close relationship between the right hepatic artery and the HC in these patients frequently limits the ability to achieve a radial R0-resection without difficult vascular reconstruction. The aim of the present study was to describe the outcome of patients who underwent pre-operative embolization of the proper hepatic artery in an effort to induce development of arterial collaterals thus allowing the resection of the proper and right hepatic artery without vascular reconstruction. Methods:, In patients presenting with HC who were considered to require a left hepatic lobectomy and in whom pre-operative work up revealed possible tumour invasion of the right hepatic artery, transcatheter arterial embolization (TAE) of the proper hepatic artery or the left and right hepatic arteries was performed. Three weeks later, a left-sided hepatectomy with resection of all portal structures except the portal vein was performed. Results:, In six patients, pre-operative embolization of the proper hepatic artery was performed. Almost instantaneously in all six patients arterial flow signals could be detected in the liver using Doppler ultrasonography. No patient died peri-operatively. In all six patients an R0 radial resection was achieved and in three an R0 proximal transection margin was obtained. All post-operative complications were managed successfully using percutaneous drainage procedures. No patient developed local recurrence and two patients remain disease free more than 7 years after surgery. Summary:, After pre-operative embolization of the proper hepatic artery, resection of the HC with left hepatectomy is a promising new approach for these technically demanding patients, giving them the chance of a cure. [source] Drug-eluting bead therapy in primary and metastatic disease of the liverHPB, Issue 7 2009Stewart Carter Abstract Background:, Drug-eluting bead transarterial chemoembolization (DEB-TACE) is a novel therapy for the treatment of hypervascuarized tumours. Through the intra-arterial delivery of microspheres, DEB-TACE allows for embolization as well as local release of chemotherapy in the treatment of hepatic malignancy, providing an alternative therapeutic option in unresectable tumours. Its role as an adjunct to surgical resection or radiofrequency ablation (RFA) is less clear. The purpose of this review is to summarize recent studies investigating DEB-TACE in order to better define safety, efficacy and outcomes associated with its use. Methods:, A systematic review of all published articles and trials identified nine clinical trials and 23 abstracts. These were reviewed for tumour histology, stage of treatment, delivery technique, outcome at follow-up, complications and mortality rates. Results:, Publications involved treatment of hepatocellular carcinoma (HCC), metastatic colorectal carcinoma (MCRC), metastatic neuroendocrine (MNE) disease and cholangiocarcinoma (CCA). Using Response Evaluation Criteria in Solid Tumours (RECIST) or European Association for the Study of the Liver (EASL) criteria, studies treating HCC reported complete response (CR) rates of 5% (5/101) at 1 month, 9% (8/91) at 4 months, 14% (19/138) at 6 months and 25% (2/8) at 10 months. Partial response (PR) was reported as 58% (76/131) at 1 month, 50% (67/119) at 4 months, 57% (62/108) at 6,7 months and 63% (5/8) at 10 months. Studies involving MCRC, CCA and MNE disease were less valuable in terms of response rate because there is a lack of comparative data. The most common procedure-associated complications included fever (46,72%), nausea and vomiting (42,47%), abdominal pain (44,80%) and liver abscess (2,3%). Rather than reporting individual symptoms, two studies reported rates of post-embolic syndrome (PES), consisting of fever, abdominal pain, and nausea and vomiting, at 82% (75/91). Six of eight studies reported length of hospital stay, which averaged 2.3 days per procedure. Mortality was reported as occurring in 10 of 456 (2%) procedures, or 10 of 214 (5%) patients. Conclusions:, Drug-eluting bead TACE is becoming more widely utilized in primary and liver-dominant metastatic disease of the liver. Outcomes of success must be expanded beyond response rates because these are not a reliable surrogate for progression-free survival or overall survival. Ongoing clinical trials will further clarify the optimal timing and strategy of this technology. [source] Utility of the Gyrus open forceps in hepatic parenchymal transectionHPB, Issue 3 2009Matthew R. Porembka Abstract Objective:, This study aimed to evaluate if the Gyrus open forceps is a safe and efficient tool for hepatic parenchymal transection. Background:, Blood loss during hepatic transection remains a significant risk factor for morbidity and mortality associated with liver surgery. Various electrosurgical devices have been engineered to reduce blood loss. The Gyrus open forceps is a bipolar cautery device which has recently been introduced into hepatic surgery. Methods:, We conducted a single-institution, retrospective review of all liver resections performed from November 2005 through November 2007. Patients undergoing resection of at least two liver segments where the Gyrus was the primary method of transection were included. Patient charts were reviewed; clinicopathological data were collected. Results:, Of the 215 open liver resections performed during the study period, 47 patients met the inclusion criteria. Mean patient age was 61 years; 34% were female. The majority required resection for malignant disease (94%); frequent indications included colorectal metastasis (66%), hepatocellular carcinoma (6%) and cholangiocarcinoma (4%). Right hemihepatectomy (49%), left hemihepatectomy (13%) and right trisectionectomy (13%) were the most frequently performed procedures. A total of 26 patients (55%) underwent a major ancillary procedure concurrently. There were no operative mortalities. Median operative time was 220 min (range 97,398 min). Inflow occlusion was required in nine patients (19%) for a median time of 12 min (range 3,30 min). Median total estimated blood loss was 400 ml (range 10,2000 ml) and 10 patients (21%) required perioperative transfusion. All patients had macroscopically negative margins. Median length of stay was 8 days. Two patients (4%) had clinically significant bile leak. The 30-day postoperative mortality was zero. Conclusions:, Use of the Gyrus open forceps appears to be a safe and efficient manner of hepatic parenchymal transection which allows rapid transection with acceptable blood loss, a low rate of perioperative transfusion, and minimal postoperative bile leak. [source] Patient preparation before surgery for cholangiocarcinomaHPB, Issue 3 2008E. Oussoultzoglou Abstract Aim. Multiorgan dysfunction is often encountered in jaundiced patients and may compromise the postoperative outcome after liver resection for cholangiocarcinoma (CCA). The aim of the present study was to elucidate evidence-based medicine regarding the benefit of the available preoperative treatments currently used for the preparation of patients before surgery for hilar CCA. Material and methods. An electronic search using the Medline database was performed to identify relevant articles relating to renal dysfunction, bacterial translocation, hemostasis impairment, malnutrition, liver failure, and postoperative outcome in jaundiced patients undergoing liver resection for CCA. Results. There is grade B evidence to expand the extracellular water volume and to administer oral synbiotic supplements. Intravenous vitamin K administration is an effective treatment. Perioperative nutritional support should be administered preferably by the enteral route in severely malnourished patients with compromised liver function undergoing extended liver resection (grade A evidence). There is only grade C evidence to recommend a portal vein embolization in patients with CCA when the future remnant liver volume is <40%. Conclusions. A simplified scheme that might be useful in the management of patients presenting with obstructive jaundice was presented. Despite surgical technique improvements, preparation of patients for surgery will continue to be one of the major determinants for the postoperative prognosis of jaundiced patients. [source] Guidelines for palliative surgery of cholangiocarcinomaHPB, Issue 3 2008H. Witzigmann Abstract The aims of the guidelines are to help assess the evidence for palliation surgery in patients with cholangiocarcinoma (CCA). The guidelines are classified in accordance with the location of the primary lesion, i.e. intrahepatic, hilar, and distal. They are based on comprehensive literature surveys, including results from randomized controlled trials, systematic reviews and meta-analysis, and cohort, prospective, and retrospective studies. Intrahepatic CCA, i.e. resection of lymph-node-positive tumors and R1/R2 resections have not been shown to provide survival benefit: Evidence levels: 2b, 4; Recommendation grade C. Hilar CCA: R1 resection is justified as a very efficient palliation. Non-surgical biliary stenting is the first choice of palliative biliary drainage. Distal CCA: Resection of lymph-node-positive tumours and R1/R2 resections should be performed. Non-surgical stenting is regarded as the first choice of palliation for patients with short life expectancy. For patients with longer projected survival, surgical bypass should be considered. Palliative resections have a relevant beneficial impact on the outcome of patients with distal and hilar CCA. Non-surgical stenting is the first choice of palliative biliary drainage for patients with hilar CCA and for those with distal CCA and short life expectancy. For patients with distal CCA and longer projected survival, surgical bypass should be considered. [source] | |||||||||||||||||||||||||||||||||||||