Diagnostic Efficacy of a Novel Rotating Brush for Endoscopic Sampling of Malignant Biliary Strictures: A Multicenter Prospective Study.

INTRODUCTION: Although cytologic examination of biliary stricture brushings obtained by endoscopic retrograde cholangiopancreatography is commonly used for diagnosing malignant biliary strictures (MBSs), it has low sensitivity. Several new brushes have capabilities that are still being debated. We have developed a novel brush working from conventional back-and-forth movement to rotation in situ (RIS) that may be more efficient for MBS sampling. We aimed to compare the MBS detection sensitivity of our RIS brush with that of the conventional brush. METHODS: In this multicenter prospective study, we enrolled patients who underwent endoscopic retrograde cholangiopancreatography for suspected MBSs involving biliary stricture brushings obtained using our RIS brush. The historical control group consisted of the 30-brushing arm of our previous randomized trial (patient inclusion, 2018-2020) that used the study design in the same centers and with the same endoscopists as were used in this study. The primary outcome was to compare the sensitivity and specificity of detecting MBSs by cytologic evaluation of biliary stricture brushings between the 2 groups. RESULTS: We enrolled 155 patients in the intent-to-treat analysis. Using the same number of brushing cycles, the RIS brush showed a higher sensitivity than the conventional brush (0.73 vs 0.56, P = 0.003). In per-protocol population, the sensitivity was also higher in the RIS brush group than in the conventional brush group (0.75 vs 0.57, P = 0.002). Multivariate analysis revealed that the RIS brush was the only predictive factor for MBS detection. No significant differences were observed in procedure-related complications between the 2 groups. DISCUSSION: The RIS brush was a promising tool for effective and safe MBS sampling and diagnosis. Further randomized studies are warranted to confirm our results (Chictr.org.cn, identifier: ChiCTR2100047270).

A New Fully Covered Self-Expandable Metal Stent for the Treatment of Postsurgical Benign Biliary Strictures.

BACKGROUND: Endotherapy with plastic stent (PS) placement is the main modality for treating benign biliary strictures (BBSs). Fully covered self-expandable metal stents (FCSEMSs) are being increasingly used for BBS management, with high stricture resolution. However, traditional metal tents are associated with high migration, causing treatment failure. METHODS: We investigated the efficacy and safety of a new FCSEMS for postsurgical BBS treatment and compared these parameters between the FCSEMS and PS treatment through retrospective analysis. The primary outcome measurements included stricture resolution, stricture recurrence, and complications. RESULTS: In total, 69 patients were included, of whom 32 underwent FCSEMS treatment and 37 underwent PS treatment. The technical success rate and the number of endoscopic retrograde cholangiopancreatography procedures were similar between the groups. The median stenting duration was 5.2 months (range 1.5-15.3) in the FCSEMS group and 10.7 months (range 2.5-22.6) in the PS group (P < 0.01). The stents removal rate was 96.9% in the FCSEMS group and 94.6% in the PS group. The stricture resolution rate based on intention-to-treat analysis was 83.8% in the PS group and 84.4% (27/32) in the FCSEMS group (P = 0.947), whereas the rates from per-protocol analysis were 88.6% (31/35) and 87.1% (27/31), respectively (P = 0.574). Early and late complications were similar between the groups. The median follow-up time was 43 months (range 13-71). The stricture recurrence rate was 11.1% (3/27) in the FCSEMS group and 16.1% (5/31) in the PS group (P = 0.435). CONCLUSIONS: The new FCSEMS and the PS approach showed similar efficacy and safety in postsurgical BBS treatment. However, the FCSEMS required fewer procedural steps and shorter stenting time, making it an effective alternative modality.

Prognostic significance of cytoskeleton-associated membrane protein 4 and its palmitoyl acyltransferase DHHC2 in hepatocellular carcinoma.

BACKGROUND: The functions of cytoskeleton-associated membrane protein 4 (CKAP4), one kind of type II transmembrane protein, are associated with the palmitoyl acyltransferase DHHC2. The objective of the current study was to investigate CKAP4/DHHC2 expression and its prognostic significance in patients with hepatocellular carcinoma (HCC). METHODS: Two independent cohorts of 416 patients with HCC were enrolled. All the patients included had defined clinicopathologic and follow-up data. Using real-time polymerase chain reaction and immunohistochemical assay, CKAP4 and DHHC2 expression were evaluated. The association between CKAP4/DHHC2 expression and HCC-specific disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses. RESULTS: The data documented that CKAP4 expression was much higher in HCC tumor tissues compared with adjacent normal tissues and its expression was significantly correlated with tumor size, intrahepatic metastases, portal venous invasion, and Barcelona Clinic Liver Cancer stage of disease in 2 cohorts of patients. On survival analysis, patients with high CKAP4 expression appeared to have a favorable overall survival and a longer disease-free survival compared with those with low expression. DHHC2 expression was also examined in tissue microarray analysis by immunohistochemistry and the results demonstrated that 87.6% of the cases had low expression of DHHC2. Kaplan-Meier analysis indicated that a high level of DHHC2 expression predicted favorable overall survival and disease-free survival rates in both the training cohort and validation set. Furthermore, the combination of CKAP4 and DHHC2 was found to have a more powerful efficiency in prognosis prediction than either one alone. CONCLUSIONS: To the best of our knowledge, the current study is the first to demonstrate that the expression of CKAP4 and its palmitoyl acyltransferase DHHC2 correlates with disease progression and metastasis in patients with HCC and may provide prognostic and therapeutic value.

Occult hepatitis B virus infection in Chinese cryptogenic intrahepatic cholangiocarcinoma patient population.

BACKGROUND: There is no information available about occult hepatitis B virus (HBV) infection (OBI) in individuals with intrahepatic cholangiocarcinoma (ICC). GOALS: To investigate the correlation between OBI and ICC. STUDY: A retrospective case-control study was conducted. The cases were 183 cryptogenic ICC patients (group I), and the controls were 549 healthy individuals (group II). The cases and controls were matched for age, sex, and inhabitancy. Adjusted odds ratios and 95% confidence intervals were calculated. Intrahepatic total HBV DNA in 63 paraffin-embedded samples was collected from patients in group I (n=44), HBV-associated ICC patients (n=3), and hepatic cavernous hemangioma patients with seronegative HBsAg (hepatitis B S antigen) (group III; n=16). We determined the levels of serum and intrahepatic HBV DNA and compared the level of intrahepatic HBV DNA in 44 cryptogenic patients from group I with the level in the patients from group III. RESULTS: Compared with group II, group I had a lower prevalence of anti-HBs (antibody against HBsAg) and a higher prevalence of anti-HBe (antibody against hepatitis B e antigen) and anti-HBc (antibody against hepatitis B c antigen). Multivariate analysis confirmed that anti-HBe and anti-HBc positivity were associated with ICC. The odds ratios and 95% confidence intervals for anti-HBe and anti-HBc were 2.482 and 1.482-4.158, 4.556 and 2.938-7.066, respectively. Compared with group III, cryptogenic ICC cases showed more frequent detection of intrahepatic total HBV DNA (63.64% vs. 18.75%, P=0.002). CONCLUSIONS: OBI may represent an important risk factor for ICC. HBsAg seroclearance does not signify eradication of HBV and may not entirely prevent the development of ICC.

Cell-free DNA methylation profiles enable early detection of colorectal and gastric cancer.

Colorectal cancer (CRC) and gastric cancer (GC) rank the top five common and lethal cancers worldwide. Early detection can significantly reduce the mortality of CRC and GC. However, current clinical screening methods including invasive endoscopic techniques and noninvasive fecal occult blood test screening tests/fecal immunochemical test have shown low sensitivity or unsatisfactory patient's compliance. Aberrant DNA methylation occurs frequently in tumorigenesis and cell-free DNA (cfDNA) methylation has shown the potential in multi-cancer detection. Herein, we aimed to explore the value of cfDNA methylation in the gastrointestinal cancer detection and develop a noninvasive method for CRC and GC detection. We applied targeted methylation sequencing on a total of 407 plasma samples from patients diagnosed with CRC, GC, and noncancerous gastrointestinal benign diseases (Non-Ca). By analyzing the methylation profiles of 34 CRC, 62 GC and 107 Non-Ca plasma samples in the training set (n=203), we identified 40,110 gastrointestinal cancer-specific markers and 63 tissue of origin (TOO) prediction markers. A new integrated model composed of gastrointestinal cancer detection and TOO prediction for three types of classification of CRC, GC and Non-Ca patients was further developed through logistic regression algorithm and validated in an independent validation set (n=103). The model achieved overall sensitivities of 83% and 81.3% at specificities of 81.5% and 80% for identifying gastrointestinal cancers in the test set and validation set, respectively. The detection sensitivities for GC and CRC were respectively 81.4% and 83.3% in the cohort of the test and validation sets. Among these true positive cancer samples, further TOO prediction showed accuracies of 95.8% and 95.8% for GC patients and accuracies of 86.7% and 93.3% for CRC patients, in test set and validation set, respectively. Collectively, we have identified novel cfDNA methylation biomarkers for CRC and GC detection and shown the promising potential of cfDNA as a noninvasive gastrointestinal cancer detection tool.

Down-regulated expression of the protein-tyrosine phosphatase 1B (PTP1B) is associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma.

The protein-tyrosine phosphatase 1B (PTP1B) is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and can exert both tumor suppressing and tumor promoting effects in different cancers depending on the substrate involved and the cellular context. However, the expression level and function of PTP1B in hepatocellular carcinoma (HCC) remain unclear. In this study, PTP1B expression was detected by immunohistochemistry in normal liver tissue (n=16) and hepatocellular carcinoma (n=169). The correlations between PTP1B expression level and clinicopathologic features and patient survival were also analyzed. One hundred and eleven of 169 HCC patients (65.7%) had negative or low PTP1B expression in tumorous tissues, whereas normal tissues always expressed strong PTP1B. Decreased PTP1B expression was significantly associated with aggressive clinicopathologic features and poor prognosis. Immunohistochemistry also showed that low PTP1B expression level was correlated with high percentage of OV6(+) tumor-initiating cells (T-ICs) and high frequency of nuclear ß-Catenin expression in HCC specimens. Our findings demonstrate for the first time that the loss of inhibitory effect of PTP1B may contribute to progression and invasion of HCC through activation of Wnt/ß-Catenin signaling and expansion of liver T-ICs. PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in HCC.

ICOSL expressed in triple-negative breast cancer can induce Foxp3+ Treg cell differentiation and reverse p38 pathway activation.

Inducible costimulator ligand (ICOSL) expressed on cancer cells has immunoregulatory functions in various malignancies. However, the role of ICOSL in triple-negative breast cancer (TNBC) remains unclear. In this study, the role and expression of ICOSL in TNBC were analyzed using the cBioPortal and GEPIA databases. Then the role of ICOSL in Foxp3+ Treg cell differentiation, reversal of p38 pathway activation and cell proliferation, migration and apoptosis was determined in vitro. Finally, the effect of ICOSL expression on TNBC progression was verified in a nude mouse model of TNBC. We here observed that ICOSL expression in TNBC was found to be related to relapse-free survival, and Treg abundance was positively correlated with ICOSL expression, as demonstrated by database analyses. In vitro experiments showed that ICOSL overexpression (OE) in MDA-MB-231 cells induced cocultured T cells to differentiate into Foxp3+ Treg cells and promoted secretion of the tumor-promoting factors IL-10 and IL-4. Furthermore, in vitro experiments showed that ICOSL reversed p38 phosphorylation and promoted the proliferation, invasion, and metastasis of MDA-MB-231 ICOSL-OE cells. Finally, tumor progression was found to be promoted by ICOSL expression in a TNBC nude mouse model. Together, ICOSL expression can enhance tumor cell growth by inducing Foxp3+ Treg cell differentiation and reversing p38 pathway activation in TNBC.

Androgens drive sexual dimorphism in liver metastasis by promoting hepatic accumulation of neutrophils.

The liver is one of the most-favored distant metastatic sites for solid tumors, and interactions between cancer cells and components of the hepatic microenvironment are essential for liver metastasis (LM). Although sex is one of the determinants for primary liver cancer, sexual dimorphism in LM (SDLM) and the underlying mechanisms remain unclear. We herein demonstrate a significant male-biased SDLM, which is attributed to host androgen/androgen receptor (Ar) signaling that promotes hepatic seeding of tumor cells and subsequent outgrowth in a neutrophil-dependent manner. Mechanistically, androgen/Ar signaling promotes hepatic accumulation of neutrophils by promoting proliferation and development of neutrophil precursors in the bone marrow, as well as modulating hepatic recruitment of neutrophils and their functions. Antagonizing the androgen/Ar/neutrophil axis significantly mitigates LM in males. Our data thus reveal an important role of androgen in LM and suggest that androgen/Ar modulation represents a promising target for LM therapy in men.

Effect of endoscopic radiofrequency ablation on the survival of patients with inoperable malignant biliary strictures: A large cohort study.

BACKGROUND AND AIMS: Endoscopic radiofrequency ablation (RFA) is an emerging technique for the palliation of inoperable malignant biliary strictures (MBSs). We aimed to systemically investigate the long-term outcome of RFA in a large cohort of patients. METHODS: We recruited 883 patients with various MBSs who underwent endoscopic interventions at two large-volume centers; 124 patients underwent RFA and stenting, whereas 759 underwent stenting alone. To overcome selection bias, we performed 1:4 propensity score matching (PSM). The main outcome was overall survival (OS). RESULTS: Following PSM, patients in the RFA group showed significantly longer OS (9.5 months; 95% CI: 7.7-11.3 months) than those in the stenting alone group (6.1 months; 95% CI: 5.6-6.6 months; P < .001). In stratified analyses, the improved OS was only demonstrated in the subgroup of extrahepatic cholangiocarcinoma (11.3 months 95% CI: 10.2-12.4 vs 6.9 months 95% CI: 6.0-7.8; P < .001), but not in the subgroups of gallbladder cancer, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, pancreatic cancer, and other metastatic cancers (all P > .05). The survival benefits were noted only in the patients with non-metastatic cholangiocarcinoma (11.5 vs 7.4 months, P < .001). CONCLUSIONS: The survival benefits of endoscopic RFA appear to be limited to patients with extrahepatic cholangiocarcinoma without distant metastasis.

Fully-covered metal stent for the treatment of post-percutaneous transhepatic biliary drainage (PTBD) obstruction due to a blood clot in the common bile duct: a case report.

AIM: This study aimed to report a case of a fully-covered metal stent for the treatment of post-Percutaneous Transhepatic Biliary Drainage (PTBD) obstruction caused by a blood clot in the common bile duct (CBD). CASE PRESENTATION: The case involved a 75-year-old man who had a history of recurring upper abdominal pain and jaundice. The result of an abdominal computerized tomography showed a stricture in the CBD. After PTBD, bleeding in the tube of PTBD was noted. The bleeding sites were detected using superselective hepatic arteriography. After the bleeding was stopped, Endoscopic Retrograde Cholangiopancreatography (ERCP) was performed to insert a fully-covered metal stent to extract the blood clot. Five months later, He was performed whipple procedure successfully and the pathology shows adenocarcinoma (cholangicarcinoma). This was the first case reported in China. CONCLUSIONS: The complications related to post-PTBD obstruction, which was caused by a blood clot in the CBD, might lead to serious health issues or even death. The blood clot could be diagnosed according to laboratory and clinical data, particularly imaging. Digital subtraction angiography (DSA) and ERCP were necessary and effective for the patient in the present case. Successfully placement of a fully-covered stent could relieve jaundice. The residual thrombus was easily extracted through the stent. This was important for the preparation of the coming procedure.

[Risk factors of intrahepatic cholangiocarcinoma: a case-control study].

OBJECTIVE: To explore the potential risk factors of intrahepatic cholangiocarcinoma (ICC) in China. METHOD: A case-control study including 317 patients with pathologically confirmed ICC and 634 healthy individuals was conducted. The cases and controls were matched in age, sex and inhabitancy. Data were statistically analyzed by Chi-square test and conditional logistic regression. RESULTS: Univariate analysis showed significant difference in HBsAg seropositivity, liver cirrhosis, hepatolithiasis, choledocholithiasis and schistosomiasis between ICC patients and healthy controls (P < 0.05). Multivariate analysis confirmed that HBsAg seropositivity, liver cirrhosis, hepatolithiasis and hepatic schistosomiasis were associated with ICC, and their adjusted odds ratio (95% confidence interval) were 10.265 (6.676-15.783), 13.101 (5.265-32.604), 18.242 (3.580-92.958), 18.435 (1.930-176.082), 15.102 (4.607-49.499) and 11.820 (3.522-39.668), respectively. The incidence of hepatic cyst, cholecystolithiasis, hepatic hemangioma, fatty liver, diabetes mellitus, smoking and drinking were not significantly different between ICC patients and controls. CONCLUSIONS: The HBV infection, liver cirrhosis, hepatolithiasis and hepatic schistosomiasis may be the risk factors for ICC in China.

Higher expression of A-kinase anchoring-protein 1 predicts poor prognosis in human hepatocellular carcinoma.

A-kinase anchoring protein 1 (AKAP1) plays important regulatory roles in the regulation of mitochondrial function, oxidative metabolism, and cell survival. However, the expression pattern and prognostic value of AKAP1 in hepatocellular carcinoma (HCC) remains unclear. AKAP1 expression levels in tumor and matched non-tumor tissues were evaluated using reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining. Kaplan-Meier and Cox regression analyses were used to analyze the survival rates. We found that AKAP1 protein expression was increased in HCC tissues, and high AKAP1 expression was associated with tumor size (P=0.024), Tumor-Node-Metastasis stage (P=0.0296) and portal vein thrombosis (P=0.00498). Kaplan-Meier survival analyses further revealed that high AKAP1 expression was associated with poor overall (P=0.004) and disease-free survival (DFS) (P=0.002) rates in patients with HCC. Multivariate survival analysis revealed that AKAP1 served as an independent poor prognostic factor for DFS rates. The findings of the present study indicated that AKAP1 expression may contribute to HCC progression. High AKAP1 expression could serve as a valuable prognostic biomarker in predicting the survival of patients with HCC following radical resection.

Identification and differential expression of human carcinoma-associated antigens in hepatocellular carcinoma tissues.

This study was designed to identify and verify hepatocellular carcinoma (HCC)-associated human carcinoma antigens (HCAs) that may be useful as tumor markers for HCC. We found that BCE075 and BCD021 anti-HCA antibodies were immunostained in the liver tissue samples and showed specific staining. Their expression was increased in HCC compared with normal liver tissues (P = 0.008). Immunoprecipitation and mass spectrometry analyses of the proteins precipitated by these two antibodies were identified to be cytoskeleton-associated protein 4 (CLIMP63) and brain-type glycogen phosphorylase (PYGB). This study demonstrated that HCC tissues expressed specific HCA glycoproteins, suggesting that our mouse monoclonal anti-HCA antibodies could be useful for immunohistochemical analysis of HCA expression as potential biomarkers for HCC diagnosis.

Role of ß-Catenin in regulating the balance between TNF-α- and Fas-induced acute liver injury.

ß-Catenin plays many critical roles during various liver physiological and pathological processes. However, the role of ß-Catenin in acute liver failure remains unclear. Using hepatocyte specific ß-Catenin knockout mice, we found that loss of ß-Catenin in hepatocyte significantly reduced GalN/LPS-induced liver damage and hepatocyte apoptosis, but exacerbated Jo2-mediated liver injury. Mechanistically, the dual effects of ß-Catenin attributes on its function of inhibiting NF-κB signaling, which aggravates oxidative stress but decreases Fas expression under injury conditions. In conclusion, ß-Catenin plays an important role in regulating the balance between TNF-α and Fas-induced liver injury via its effect on NF-κB.

Hepatitis B virus infection: a favorable prognostic factor for intrahepatic cholangiocarcinoma after resection.

AIM: To study the prognostic factors for intrahepatic cholangiocarcinoma (ICC) and evaluate the impact of chronic hepatitis B virus (HBV) infection on survival rate of ICC patients. METHODS: A total of 155 ICC patients who underwent macroscopic curative resections (R0 and R1) were enrolled in this retrospective study and divided into group A with HBV infection and group B without HBV infection according to their chronic HBV infection, represented by positive hepatitis B surface antigen (HBsAg) in serum or in liver tissue. Clinicopathological characteristics and survival rate of the patients were evaluated. RESULTS: All patients underwent anatomical resection. Their 1- and 3-year survival rates were 60.6% and 32.1%, respectively. Multivariate analyses revealed that HBV infection, hepatolithiasis, microscopic satellite lesion, and lymphatic metastasis were the independent prognostic factors for the survival rate of ICC patients. The median disease-free survival time of the patients was 5.0 mo. The number of tumors, microscopic satellite lesion, and vascular invasion were the independent prognostic factors for the disease-free survival rate of the patients. The prognostic factors affecting the survival rate of ICC patients with HBV infection and those without HBV infection were not completely consistent. Alkaline phosphatase > 119 U/L, microscopic satellite lesion, vascular invasion, and lymphatic metastasis were the independent factors for the patients with HBV infection, while r-glutamyltransferase > 64 U/L, microscopic satellite lesion, and poor tumor differentiation were the independent factors for the patients without HBV infection. CONCLUSION: HBV infection is a valuable clinical factor for predicting tumor invasiveness and clinical outcome of ICC patients. ICC patients with HBV infection should be distinguished from those without HBV infection because they have different clinicopathological characteristics, prognostic factors and outcomes after surgical resection.

Etiological and clinicopathologic characteristics of intrahepatic cholangiocarcinoma in young patients.

AIM: To investigate the prevalence, risk factors, and clinicopathologic characteristics of intrahepatic cholangiocarcinoma (ICC) in young patients. METHODS: A retrospective analysis was performed in ICC patients referred to the Eastern Hepatobiliary Surgery Hospital in Shanghai, China. Among 317 consecutively enrolled patients, 40 patients were aged 40 years (group II: n = 277). RESULTS: Group I had distinct features compared with group II, including a low frequency of hepatolithiasis (P = 0.000); a high positive rate of serum hepatitis B surface antigen (P = 0.000) and hepatitis B virus (HBV)-associated cirrhosis (P = 0.038); a high frequency of alpha-fetoprotein (> 400 microg/L) (P = 0.011); a low frequency of carbohydrate antigen 19-9 (> 37 U/mL) (P = 0.017); and a high frequency of liver histological inflammation (P = 0.002). Although there was no significant difference between the two groups in regards to hepatic schistosomiasis, alcohol-associated cirrhosis and cirrhosis due to other causes (P > 0.05), they only occurred in the elderly group. CONCLUSION: The risk factors are significantly different between young and elderly ICC patients. HBV and HBV-associated cirrhosis are the most important risk factors for young ICC patients.

Hepatitis B virus-associated intrahepatic cholangiocarcinoma and hepatocellular carcinoma may hold common disease process for carcinogenesis.

AIMS: To evaluate potential risk factors for intrahepatic cholangiocarcinoma (ICC) and analyse clinicopathologic characteristics of ICC patients with seropositive hepatitis B surface antigen (HBsAg). METHODS: A retrospective case-control study was conducted. Cases were 317 ICC patients referred to the Eastern Hepatobiliary Surgery Hospital in China between 2003 and 2006. Controls were 634 healthy individuals. Adjusted odds ratios (ORs) were calculated in logistic regression analysis. Among 317 consecutively enrolled ICC patients, 154 patients were seropositive HBsAg (48.6%). We compared clinicopathologic characteristics of these patients (group I) with ICC patients seronegative for HBsAg (group II; n=163) and compared the age and sex distributions of patients in group I with randomly selected hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) (group III; n=1,140). RESULTS: Compared with the controls, ICC patients had a high prevalence of seropositive HBsAg, cirrhosis, hepatolithiasis and hepatic schistosomiasis. Compared with seronegative-HBsAg ICC patients, seropositive-HBsAg ICC patients were younger, more frequently male and had a higher proportion of abnormal aminotransferase and serum alpha-fetoprotein (AFP) level, histological inflammation and cirrhosis, right-lobe focus, poor tumour differentiation, tumour encapsulation and microvascular invasion; had a lower proportion of abnormal serum carbohydrate antigen 19-9 (CA19-9) level and lymphatic metastasis. The age and sex distribution profiles were nearly identical between seropositive-HBsAg ICC patients and HBV-associated HCC patients. CONCLUSIONS: The HBV infection, cirrhosis, hepatolithiasis and hepatic schistosomiasis may be potential risk factors for ICC. HBV-associated ICC shares many clinicopathological similarities with HBV-associated HCC. The result indicated HBV-associated ICC and HBV-associated HCC may hold common disease process for carcinogenesis.