Objective To investigate the expression and the potential roles of long non-coding RNA(lncRNA)cancer susceptibility candidate 2(CASC2)and imprinted gene H19 in extrahepatic cholangiocarcinoma(ECC). Methods Four samples from patients with ECC were collected for high-throughput sequencing which was conducted to reveal the transcriptomic profiles of lncRNA CASC2 and H19.Bioinformatics tools were employed to predict the potential roles of the two genes.Another 22 ECC tissue samples and the cholangiocarcinoma cell lines(RBE,QBC939,HuH-28,and HuCCT1)with different degrees of differentiation were selected for validation.The para-carcinoma tissue and normal human intrahepatic biliary epithelial cell(HIBEC)were used as the control groups.The expression levels of lncRNA CASC2 and H19 in carcinoma tissue,para-carcinoma tissue,and cell lines were determined by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation analysis was carried out for the clinical indicators of patients with the expression levels of the target genes. Results The two target genes showed significantly different expression between carcinoma tissue and para-carcinoma tissue(all P<0.05).Specifically,CASC2 had higher expression level in the carcinoma tissue than in the para-carcinoma tissue(t=1.262,P=0.025),whereas the expression of H19 showed an opposite trend(t=1.285,P=0.005).The expression levels of CASC2 in QBC939(t=8.114,P=0.015)and HuH-28(t=9.202,P=0.012)cells were significantly higher than that in the control group.The expression levels of H19 were significantly lower in RBE(t=-10.244,P<0.001),QBC939(t=-10.476,P<0.001),HuH-28(t=-19.798,P<0.001),and HuCCT1(t=-16.193,P=0.004)cells than in the control group.Bioinformatics analysis showed that CASC2 was mainly involved in the metabolic process and H19 in the development of multicellular organisms.Both CASC2 and H19 were related to catalytic activity.The expression level of lncRNA CASC2 was correlated with pathological differentiation(χ ²=6.222,P=0.022)and lymph node metastasis(χ²=5.455,P=0.020),and that of lncRNA H19 with pathological differentiation(χ²=1.174,P=0.029)and tumor size(χ²=-0.507,P=0.037). Conclusions In the case of ECC,lncRNA CASC2 and H19 have transcription disorders.lncRNA CASC2 is generally up-regulated in the carcinoma tissue,while H19 is down-regulated.Both genes have the potential to become new molecular markers for ECC.
Bile Duct Neoplasms/genetics* ; Bile Ducts, Intrahepatic/metabolism* ; Cholangiocarcinoma/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; RNA, Long Noncoding/genetics* ; Tumor Suppressor Proteins/genetics*

PURPOSE: In intrahepatic cholangiocarcinoma (iCCA), genetic characteristics on ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-PET scans are not yet clarified. If specific genetic characteristics were found to be related to FDG uptake in iCCA, we can predict molecular features based on the FDG uptake patterns and to distinguish different types of treatments. In this purpose, we analyzed RNA sequencing in iCCA patients to evaluate gene expression signatures associated with FDG uptake patterns. METHODS: We performed RNA sequencing of 22 cases iCCA who underwent preoperative ¹⁸F-FDG-PET, and analyzed the clinical and molecular features according to the maximum standard uptake value (SUVmax). Genes and biological pathway which are associated with SUVmax were analyzed. RESULTS: Patients with SUVmax higher than 9.0 (n = 9) had poorer disease-free survival than those with lower SUVmax (n = 13, P = 0.035). Genes related to glycolysis and gluconeogenesis, phosphorylation and cell cycle were significantly correlated with SUVmax (r ≥ 0.5). RRM2, which is related to the toxicity of Gemcitabine was positively correlated with SUVmax, and SLC27A2 which is associated with Cisplastin response was negatively correlated with SUVmax. According to the pathway analysis, cell cycle, cell division, hypoxia, inflammatory, and metabolism-related pathways were enriched in high SUVmax patients. CONCLUSION: The genomic features of gene expression and pathways can be predicted by FDG uptake features in iCCA. Patients with high FDG uptake have enriched cell cycle, metabolism and hypoxic pathways, which may lead to a more rational targeted treatment approach.
Anoxia ; Cell Cycle ; Cell Division ; Cholangiocarcinoma ; Disease-Free Survival ; Fluorodeoxyglucose F18 ; Gene Expression ; Gluconeogenesis ; Glycolysis ; Humans ; Metabolism ; Phosphorylation ; Positron-Emission Tomography ; Sequence Analysis, RNA ; Transcriptome

No abstract available.
Adult ; Anterior Temporal Lobectomy ; Bile Duct Neoplasms/*diagnostic imaging/surgery ; *Bile Ducts, Intrahepatic/surgery ; Carcinoma, Hepatocellular/diagnostic imaging ; Cholangiocarcinoma/*diagnostic imaging/surgery ; Cholangiopancreatography, Magnetic Resonance ; Diagnosis, Differential ; Humans ; Liver/diagnostic imaging/metabolism ; Liver Neoplasms/diagnostic imaging ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed

OBJECTIVETo study the clinicopathologic features of combined hepatocellular-cholangiocarcinoma (cholangiolocellular type, CLC type) with stem cell features and its relationship to hepatic progenitor cells (HPCs).

METHODSClinical and histologic features of 26 cases of combined hepatocellular-cholangiocarcinoma (CLC type) were reviewed. Histochemistry was performed to confirm the type of mucin and immunohistochemical study was carried out for hepatocytic markers (Hep Par-1 and AFP) and biliary/HPCs markers (CK7, CK9, EMA, EpCAM, NCAM, CKIT).

RESULTSThe age of patients ranged from 51 to 82 years (mean 64 years). All 26 cases contained CLC and hepatocellular carcinoma components. CLC area was composed of mixtures of small monotonous glands with abundant fibrous stroma and lymphocytic infiltrate. Tumor cells were cuboidal, smaller in size than normal hepatocytes, with basophilic cytoplasm and round nuclei. All cases, especially at the tumor boundary, showed HCC-like trabecular areas characterized by mildly atypical tumor cells with abundant eosinophilic cytoplasm and little stroma. Out of 26 cases, 21 showed definite glandular formation with mucin production, representing intrahepatic cholangiocarcinoma areas. The three distinct areas showed transitional zones merging with each other. The surrounding liver tissue showed cirrhosis and chronic hepatitis with varying degrees of fibrosis and periportal ductular reaction. Immunohistochemistry showed that biliary/HPC markers (CK7, CK9, EMA, EpCAM, NCAM and CKIT) were strongly positive in CLC area in almost all cases, similar to the staining pattern of ductular reaction. In HCC-like areas, CK7 and CK19 were positive in all cases and the expression rates of EMA, EpCAM, NCAM, CKIT, AFP, Hep Par-1 were 80.8% (21/26), 88.5% (23/26), 84.6% (22/26), 88.5% (23/26), 46.2% (12/26) and 53.8% (14/26) respectively, similar to the staining pattern of intermediate hepatocytes. In ICC areas, CK7, CK9, EMA and EpCAM were positive in all cases without the expression of NCAM and CKIT.

CONCLUSIONThe clinicopathologic findings and immunohistochemical results in this study highly suggest a hepatic progenitor cell origin of combined hepatocellular-cholangiocarcinoma (CLC type).

Bile Duct Neoplasms ; pathology ; Biomarkers ; metabolism ; Carcinoma, Hepatocellular ; pathology ; Cholangiocarcinoma ; pathology ; Hepatocytes ; cytology ; Humans ; Immunohistochemistry ; Liver Cirrhosis ; pathology ; Liver Neoplasms ; pathology ; Mucins ; metabolism ; Stem Cells ; cytology

No abstract available.
Bile Ducts, Intrahepatic ; Cell Differentiation ; Cholangiocarcinoma/*pathology ; Humans ; Immunohistochemistry ; Keratin-19/metabolism ; Liver Neoplasms/*pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Tomography, X-Ray Computed

No abstract available.
Aged ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Cadherins/metabolism ; Cholangiocarcinoma/*pathology/radiography ; Female ; Giant Cells/metabolism/*pathology/radiography ; Humans ; Osteoclasts/pathology ; Tomography, X-Ray Computed

Bi-phenotypic neoplasm refers to tumors derived from a common cancer stem cell with unique capability to differentiate histologically into two distinct tumor types. Bi-phenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC), although a rare tumor, is important for clinicians to recognize, since treatment options targeting both elements of the tumor are crucial. Imaging findings of bi-phenotypic HCC-CC are not specific and include features of both HCC and CC. A combination of imaging and immuno-histochemical analysis is usually needed to make the diagnosis.
CA-19-9 Antigen/metabolism ; Carcinoma, Hepatocellular/mortality/pathology/radiography ; Cholangiocarcinoma/mortality/pathology/radiography ; Humans ; Liver Neoplasms/mortality/pathology/*radiography ; Magnetic Resonance Imaging ; Phenotype ; Risk Factors ; Survival Analysis ; Tomography, X-Ray Computed ; alpha-Fetoproteins/analysis

BACKGROUND/AIMS: Biliary drainage is performed in many patients with cholangiocarcinoma (CCA) to relieve obstructive jaundice. For those who have undergone biliary drainage, bile cytology can be easily performed since the access is already achieved. This study aims to determine the clinical usefulness of bile cytology for the diagnosis of CCA and to evaluate factors affecting its diagnostic yield. METHODS: A total of 766 consecutive patients with CCA underwent bile cytology via endoscopic nasobiliary drainage or percutaneous transhepatic biliary drainage from January 2000 to June 2012. Data were collected by retrospectively reviewing the medical records. We evaluated the diagnostic yield of bile cytology with/without other sampling methods including brush cytology and endobiliary forcep biopsy, and the optimal number of repeated bile sampling. Several factors affecting diagnostic yield were then analyzed. RESULTS: The sensitivity of bile cytology, endobiliary forceps biopsy, and a combination of both sampling methods were 24.7% (189/766), 74.4% (259/348), and 77.9% (271/348), respectively. The cumulative positive rate of bile sampling increased from 40.7% (77/189) at first sampling to 93.1% (176/189) at third sampling. On multivariate analysis, factors associated with positive bile cytology were perihilar tumor location, intraductal growing tumor type, tumor extent > or =20 mm, poorly differentiated grade tumor, and three or more samplings. CONCLUSIONS: Although bile cytology itself has a low sensitivity in diagnosing CCA, it has an additive role when combined with endobiliary forceps biopsy. Due to the relative ease and low cost, bile cytology can be considered a reasonable complementary diagnostic tool for diagnosing CCA.
Aged ; Bile/*cytology ; Bile Duct Neoplasms/*diagnosis/pathology/radiography ; CA-19-9 Antigen/metabolism ; Cholangiocarcinoma/*diagnosis/pathology/radiography ; Drainage ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Retrospective Studies

OBJECTIVETo study the correlation between clinicopathological features and serum carbohydrate antigen 19-9 (CA19-9)/carcinoembryonic antigen (CEA) in patients with extrahepatic cholangiocarcinoma (ECC).

METHODSThe clinicopathological data of 126 cases of extrahepatic cholangiocarcinoma treated in our department from Jan. 1999 to Dec. 2012 were collected and analyzed in this study. The correlation between clinicopathological features and sensitivity of CA19-9/CEA was analyzed by chi-square test. The correlation of clinicopathological features and value of serum CA19-9/CEA was analyzed by t test and F test.

RESULTSThe average value of CA19-9 before surgery in the 126 patients was 595.3 U/ml. The values of CA19-9 in 91 patients were abnormal and the sensitivity of CA19-9 was 72.2%. The average value of CEA before surgery was 12.6 U/ml. The value of CEA in 26 patients were abnormal and the sensitivity of CEA was 20.6%. The values of combined detection of serum CA19-9 and CEA before surgery were abnormal in a total of 97 cases with a sensitivity of 77.0%. There was no significant correlation between clinicopathological features and sensitivity of CA19-9 (P > 0.05). The location of tumor was significantly correlated to the diagnostic sensitivity of CEA. The sensitivity of CEA to distal ECC was only 15.4%. The value of CA19-9 was relatively high in patients >60-year old or with neural invasion, while CEA was higher when tumor was located in the middle of bile duct (P < 0.05). There was no significant difference of serum CA19-9 before and after jaundice reduction (P > 0.05).

CONCLUSIONSThe diagnostic sensitivity of CA19-9 is not affected by gender, age, blood type, tumor location, degree of differentiation, tumor size, T stage, vascular tumor thrombus, lymph node metastasis, perineural invasion, and preoperative jaundice. However, the diagnostic sensitivity of CEA is affected by tumor location. The value of CA19-9 is correlated with tumor invasion and is relatively high in patients above 60 years old.

Bile Duct Neoplasms ; metabolism ; pathology ; Bile Ducts, Intrahepatic ; metabolism ; pathology ; Biomarkers, Tumor ; metabolism ; CA-19-9 Antigen ; metabolism ; Carcinoembryonic Antigen ; metabolism ; Cholangiocarcinoma ; metabolism ; pathology ; Humans ; Lymphatic Metastasis

No abstract available.
Aged ; Bile Duct Neoplasms/metabolism/*pathology ; Bile Ducts, Intrahepatic/metabolism/*pathology ; Cholangiocarcinoma/metabolism/*pathology ; Humans ; Immunohistochemistry ; Keratin-19/metabolism ; Male ; Positron-Emission Tomography ; Tomography, X-Ray Computed