Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea

BACKGROUND Intrahepatic duct(IHD)stones are among the most important risk factors for cholangiocarcinoma(CCC).Approximately 10%of patients with IHD stones develop CCC;however,there are limited studies regarding the effect of IHD stone removal on CCC development.AIM To investigate the association between IHD stone removal and CCC development.METHODS We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020.RESULTS CCC occurred in 36 of the 397 enrolled patients.In univariate analysis,chronic hepatitis B infection(11.1%vs 3.0%,P=0.03),carbohydrate antigen 19-9(CA19-9,176.00 vs 11.96 II/mL,P=0.010),stone located in left or both lobes(86.1%vs 70.1%,P=0.042),focal atrophy(52.8%vs 26.9%,P=0.001),duct stricture(47.2%vs 24.9%,P=0.004),and removal status of IHD stone(33.3%vs 63.2%,P<0.001)were significantly different between IHD stone patients with and without CCC.In the multivariate analysis,CA19-9>upper normal limit,carcinoembryonic antigen>upper normal limit,stones located in the left or both lobes,focal atrophy,and complete removal of IHD stones without recurrence were independent factors influencing CCC development.However,the type of removal method was not associated with CCC risk.CONCLUSION Complete removal of IHD stones without recurrence could reduce CCC risk.

感兴趣区范围对MRI影像组学模型预测ICC分化程度的影响

目的探讨不同感兴趣(ROI)范围对MRI影像组学模型预测肝内胆管细胞癌(ICC)病理分化程度的影响。方法回顾性收集经术后病理证实的ICC患者191例,按照7:3的比例随机分为训练组(n=133)和验证组(n=58)。两位医师在MRI平扫及增强序列上沿肿瘤边缘手动逐层勾画ROI,随后由软件自动外扩8、10、12mm并手动调整,得到ROItumor、ROI 8mm、ROI 10mm、ROI 12mm。分别提取以上4种ROI的组学特征,经过最小绝对收缩和选择算子(LASSO)筛选特征,利用逻辑回归建立模型,并用验证组进行验证。最后采用特征曲线下面积(AUC)、校准曲线及决策曲线对模型效能进行综合评估。结果验证组10mm模型AUC最高为0.754。Hosmer-Lemeshow检验所有模型校准曲线均表现良好(P>0.05)。决策曲线显示当阈值为0.24时,获益最高为10mm模型。结论ROI范围的选择对MRI影像组学模型预测ICC的分化程度有一定影响,10mm可能为最佳范围。

MMP14 is a diagnostic gene of intrahepatic cholangiocarcinoma associated with immune cell infiltration

BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor of the hepatobiliary system with concealed onset,strong invasiveness and poor prognosis.AIM To explore the disease characteristic genes that may be helpful in the diagnosis of ICC and affect immune cell infiltration.METHODS We downloaded two ICC-related human gene expression profiles from GEO database as the training group(GSE26566 and GSE32958 datasets)for difference analysis,and performed enrichment analysis on differential genes.The least absolute shrinkage and selection operator(LASSO),support vector machinerecursive feature elimination(SVM-RFE)and random forest(RF),three machine learning algorithms,were used to screen the characteristic genes.Double verification was carried out on GSE107943 and The Cancer Genome Atlas,two verification groups.Receiver operating characteristic curve and area under the curve(AUC)were used to evaluate the diagnostic efficacy of genes for ICC.CIBERSORT and ssGSEA algorithms were used to evaluate the effect of characteristic genes on immune infiltration pattern.Human Protein Atlas(HPA)was used to analyze the protein expression level of the target gene.RESULTS A total of 1091 differential genes were obtained in the training group.Enrichment analysis showed that the above genes were mainly enriched in small molecular catabolism,complement and coagulation cascade,bile secretion and other functions and pathways.Twentyfive characteristic genes were screened by LASSO regression,19 by SVM-RFE algorithm,and 30 by RF algorithm.Three algorithms were used in combination to determine the characteristic gene of ICC:MMP14.The verification group confirmed that the genes had a high diagnostic accuracy(AUC values of the training group and the verification group were 0.960,0.999,and 0.977,respectively).Comprehensive analysis of immune infiltration showed that MMP14 could affect the infiltration of monocytes,activated memory CD4 T cells,resting memory CD4 T cells,and other immune cells,and was closely related to the expression of CD200,cytotoxic T-lymphocyteassociated antigen 4,CD14,CD44,and other immune checkpoints.The results of immunohistochemistry in HPA database showed was indeed overexpressed in ICC.CONCLUSION MMP14 can be used as a disease characteristic gene of ICC,and may regulate the distribution of immune-infiltrating cells in the ICC tumor microenvironment,which provides a new method for the determination of ICC diagnostic markers and screening of therapeutic targets.

Solid-Tubulocystic carcinoma:A new variant of intrahepatic cholangiocarcinoma

A new variant of intrahepatic cholangiocarcinoma(iCCA)has been recognized in recent years presenting predominantly as a large hepatic mass in young woman with the characteristic expression of inhibin by immunohistochemistry.This variant iCCA was originally termed as cholangioblastic variant of iCCA,and subsequently proposed to be renamed as inhibin-positive hepatic carcinoma or solid-tubulocystic variant of iCCA to better reflect its immunohistochemical profile or morphologic spectrum.The tumor histologically is composed of small to medium sized cells with scant to moderate amount of eosinophilic cytoplasm heterogeneously organized in solid,tubular,and cystic growth patterns.The tumor cells are positive for biliary markers,inhibin and albumin,and have a novel recurrent gene fusion,NIPBL::NACC1.Awareness of this new iCCA variant and its clinicopathologic features will aid in the diagnostic work-up and avoid confusion with other primary and metastatic hepatic neoplasms.

Any role for transarterial radioembolization in unresectable intrahepatic cholangiocarcinoma in the era of advanced systemic therapies?

Intrahepatic cholangiocarcinoma(iCCA)is recognized as the second most frequently diagnosed liver malignancy,following closely after hepatocellular carcinoma.Its incidence has seen a global upsurge in the past several years.Unfortunately,due to the lack of well-defined risk factors and limited diagnostic tools,iCCA is often diagnosed at an advanced stage,resulting in a poor prognosis.While surgery is the only potentially curative option,it is rarely feasible.Currently,there are ongoing investigations into various treatment approaches for unresectable iCCA,including conventional chemotherapies,targeted therapies,immunotherapies,and locoregional treatments.This study aims to explore the role of transarterial radioembolization(TARE)in the treatment of unresectable iCCA and provide a comprehensive review.The findings suggest that TARE is a safe and effective treatment option for unresectable iCCA,with a median overall survival(OS)of 14.9 months in the study cohort.Studies on TARE for unresectable iCCA,both as a first-line treatment(as a neo-adjuvant down-staging strategy)and as adjuvant therapy,have reported varying median response rates(ranging from 34%to 86%)and median OS(12-16 mo).These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the studies.Most studies have identified tumor burden,portal vein involvement,and the patient’s performance status as key prognostic factors.Furthermore,a phase 2 trial evaluated the combination of TARE and chemotherapy(cisplatin-gemcitabine)as a first-line therapy for locally advanced unresectable iCCA.The results showed promising outcomes,including a median OS of 22 mo and a 22%achievement in down-staging the tumor.In conclusion,TARE represents a viable treatment option for unresectable iCCA,and its combination with systemic chemotherapy has shown promising results.However,it is important to consider treatment-independent factors that can influence prognosis.Further research is necessary to identify optimal treatment combinations and predictive factors for a favorable response in iCCA patients.

Intrahepatic cholangiocarcinoma in patients with primary sclerosing cholangitis and ulcerative colitis: Two case reports

BACKGROUND Primary sclerosing cholangitis(PSC)is an extraintestinal manifestation of ulcerative colitis(UC).PSC is a well-known risk factor for intrahepatic cholangiocarcinoma(ICC),and ICC is known to have a poor prognosis.CASE SUMMARY We present two cases of ICC in patients with PSC associated with UC.In the first case,a tumor was found by magnetic resonance imaging(MRI)in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain.The second patient was asymptomatic,but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC.ICC was strongly suspected by computed tomography and MRI in both cases,and surgery was performed,but unfortunately,the first patient died of ICC recurrence 16 mo postoperatively,and the second patient died of liver failure 14 mo postoperatively.CONCLUSION Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.

Hepatolithiasis and intrahepatic cholangiocarcinoma: A review

Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis is an established risk factor for cholangiocarcinoma(CCA), and chronic proliferative inflammation may be involved in biliary carcinogenesis and in inducing the upregulation of cell-proliferating factors. With the use of advanced imaging modalities, there has been much improvement in the management of hepatolithiasis and the diagnosis of hepatolithiasis-associated CCA(HLCCA). However, there are many problems in managing the strictures in hepatolithiasis and differentiating them from infiltrating types of CCA. Surgical resection is recommended in cases of single lobe hepatolithiasis with atrophy, uncontrolled stricture, symptom duration of more than 10 years, and long history of biliaryenteric anastomosis. Even after resection, patients should be followed with caution for development of HL-CCA, because HL-CCA is an independent prognostic factor for survival. It is not yet clear whether hepatic resection can reduce the occurrence of subsequent HL-CCA. Furthermore, there are no consistent findings regarding prediction of subsequent HL-CCA in patients with hepatolithiasis. In the management of hepatolithiasis, important factors are the reduction of recurrence of cholangitis and suspicion of unrecognized HL-CCA.

Routine lymph node dissection may be not suitable for all intrahepatic cholangiocarcinoma patients: Results of a monocentric series

AIM:To investigate the indications for lymph node dissection(LND)in intrahepatic cholangiocarcinoma patients.METHODS:A retrospective analysis was conducted on 124 intrahepatic cholangiocarcinoma(ICC)patients who had undergone surgical resection of ICC from January 2006 to December 2007.Curative resection was attempted for all patients unless there were metastases to lymph nodes(LNs)beyond the hepatoduodenal ligament.Prophylactic LND was performed in patients in whom any enlarged LNs had been suspicious for metastases.The patients were classified according to the LND and LN metastases.Clinicopathologic,operative,and long-term survival data were collected retrospectively.The impact on survival of LND during primary resection was analyzed.RESULTS:Of 53 patients who had undergone hepatic resection with curative intent combined with regional LND,11 had lymph nodes metastases.Whether or not patients without lymph node involvement had undergone LND made no significant difference to their survival(P=0.822).Five patients with multiple tumors and involvement of lymph nodes underwent hepatic resection with LND;their survival curve did not differ significantly from that of the palliative resection group(P=0.744).However,there were significant differences in survival between patients with lymph node involvement and a solitary tumor who underwent hepatic resection with LND and the palliative resection group(median survival time 12 mo vs 6.0 mo,P=0.013).CONCLUSION:ICC patients without lymph node involvement and patients with multiple tumors and lymph node metastases may not benefit from aggressive lymphadenectomy.Routine LND should be considered with discretion.

Pathological classification of intrahepatic cholangiocarcinoma based on a new concept

Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma.Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC.

Prognosis after resection for hepatitis B virus-associated intrahepatic cholangiocarcinoma

AIM:To investigate the prognostic factors after resection for hepatitis B virus(HBV)-associated intrahepatic cholangiocarcinoma(ICC) and to assess the impact of different extents of lymphadenectomy on patient survival.METHODS:A total of 85 patients with HBV-associated ICC who underwent curative resection from January 2005 to December 2006 were analyzed.The patients were classified into groups according to the extent of lymphadenectomy(no lymph node dissection,sampling lymph node dissection and regional lymph node dissection).Clinicopathological characteristics and survival were reviewed retrospectively.RESULTS:The cumulative 1-,3-,and 5-year survival rates were found to be 60 %,18 %,and 13 %,respectively.Multivariate analysis revealed that liver cirrhosis(HR = 1.875,95%CI:1.197-3.278,P = 0.008) and multiple tumors(HR = 2.653,95%CI:1.562-4.508,P < 0.001) were independent prognostic factors for survival.Recurrence occurred in 70 patients.The 1-,3-,and 5-year disease-free survival rates were 36%,3% and 0%,respectively.Liver cirrhosis(HR = 1.919,P = 0.012),advanced TNM stage(stage Ⅲ/Ⅳ)(HR = 2.027,P < 0.001),and vascular invasion(HR = 3.779,P = 0.02) were independent prognostic factors for disease-free survival.Patients with regional lymph node dissection demonstrated a similar survival rate to patients with sampling lymph node dissection.Lymphadenectomy did not significantly improve the survival rate of patients with negative lymph node status.CONCLUSION:The extent of lymphadenectomy does not seem to have influence on the survival of patients with HBV-associated ICC,and routine lymph nodedissection is not recommended,particularly for those without lymph node metastasis.

Differentiation of intrahepatic cholangiocarcinoma from hepatocellular carcinoma in high-risk patients: a predictive model using contrast-enhanced ultrasound

AIM To develop a contrast-enhanced ultrasound(CEUS)predictive model for distinguishing intrahepatic cholangiocarcinoma(ICC) from hepatocellular carcinoma(HCC) in high-risk patients.METHODS This retrospective study consisted of 88 consecutive high-risk patients with ICC and 88 high-risk patients with HCC selected by propensity score matching between May 2004 and July 2016. Patients were assigned to two groups, namely, a training set and validation set, at a 1:1 ratio. A CEUS score for diagnosing ICC was generated based on significant CEUS features. Then, a nomogram based on the CEUS score was developed, integrating the clinical data. The performance of the nomogram was then validated and compared with that of the LR-M of the CEUS Liver Imaging Reporting and Data System(LI-RADS).RESULTS The most useful CEUS features for ICC were as follows: rim enhancement(64.5%), early washout(91.9%), intratumoral vein(58.1%), obscure boundary of intratumoral non-enhanced area(64.5%), and marked washout(61.3%, all P < 0.05). In the validation set, the area under the curve(AUC) of the CEUS score(AUC = 0.953) for differentiation between ICC and HCC was improved compared to the LI-RADS(AUC = 0.742)(P < 0.001). When clinical data were added, the CEUS score nomogram was superior to the LI-RADS nomogram(AUC: 0.973 vs 0.916, P = 0.036, Net Reclassification Improvement: 0.077, Integrated Discrimination Index: 0.152). Subgroup analysis demonstrated that the CEUS score model was notably improved compared to the LIRADS in tumors smaller than 5.0 cm(P < 0.05) but not improved in tumors smaller than 3.0 cm(P > 0.05).CONCLUSION The CEUS predictive model for differentiation between ICC and HCC in high-risk patients had improved discrimination and clinical usefulness compared to the CEUS LIRADS.

Hepatitis B virus and hepatitis C virus play different prognostic roles in intrahepatic cholangiocarcinoma: A meta-analysis

AIM: To identify the prognostic value of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections in patients with intrahepatic cholangiocarcinoma.METHODS: A search was performed for relevant publications in Pub Med, EMBASE and Web of Science databases. The pooled effects were calculated from the available information to identify the relationship between HBV or HCV infection and the prognosis and clinicopathological features. The χ2 and I2 tests were used to evaluate heterogeneity between studies. Pooled hazard ratios(HRs) with 95% confidence intervals(CIs) were calculated by a fixed-effects model, if no heterogeneity existed. If there was heterogeneity, a random-effects model was applied.RESULTS: In total, 14 studies involving 2842 cases were enrolled in this meta-analysis. The patients with HBV infection presented better overall and diseasefree survival, and the pooled HRs were significant at 0.76(95%CI: 0.70-0.83) and 0.78(95%CI: 0.66-0.94), respectively. Additionally, our study revealed that HCV infection was correlated with shortened overall survival in comparison with the control group(HR = 2.64, 95%CI: 1.77-3.93). We also found that HBV infection occurred more frequently in male patients [odds ratio(OR) = 1.91, 95%CI: 1.06-3.44] and was correlated with higher levels of serum aspartate transaminase(AST) and alpha-fetoprotein(AFP)(OR = 1.93, 95%CI: 1.11-3.35; OR = 3.86, 95%CI: 2.58-5.78) and a lower level of serum carbohydrate antigen 19-9(CA19-9)(OR = 0.47, 95%CI: 0.34-0.65). Moreover, HBV infection was associated with cirrhosis(OR = 6.44, 95%CI: 4.33-9.56), a higher proportion of capsule formation(OR = 6.04, 95%CI: 3.56-10.26), and a lower rate of lymph node metastasis(OR = 0.39, 95%CI: 0.25-0.58). No significant publication bias was seen in any of the enrolled studies.CONCLUSION: HBV infection may indicate a favorable prognosis in patients with intrahepatic cholangiocarcinoma, while HCV infection suggests a poor prognosis.

Clinicopathologic features, diagnosis and surgical treatment of intrahepatic cholangiocarcinoma in 104 patients

BACKGROUND: The outcome of surgical treatment of pa- tients with intrahepatic cholangiocarcinoma (ICC) is poor. This study was designed to analyze the relationship between clinicopathologic features and the survival time after opera- tion. METHODS: The operation was performed in 104 patients with mass-forming type ICC at our hospital between No- vember 1996 and May 2000. Seventy-nine patients (76.0%) were followed up successfully. Sixteen clinicopathological variables including age, sex, history of chronic liver di- sease , HBsAg, operation, adjuvant therapy, ascites, lymph node metastasis, invasion of adjacent organs, tumor size, necrosis of tumor, envelope, intrahepatic metastasis, Inter- national Union Against Cancer (UICC) TNM staging, his- tology, and cirrhosis were selected for univariate and multi- variate analyses to evaluate their influence on the prognosis. RESULTS: The accumulative 1-, 3-, 5-year survival rates of the 79 patients were 49.4%, 17.3%, 9.6% respectively. Univariate analysis revealed that sex (P=0.0221), HBsAg (P=0.0115), operation (P=0.0042), adjuvant therapy (P= 0.0389), ascites (P=0.0001), invasion (P=0.0220), intra- hepatic metastasis (P=0.0000) and TNM stage (P= 0.0001) were related to survival time. Multivariate analysis revealed that HBsAg, ascites and TNM stage were signifi- cantly related to prognosis. CONCLUSION: Early diagnosis and treatment and major hepatectomy are essential to improving the results of surgi- cal treatment of ICC patients.

Analysis of intrahepatic sarcomatoid cholangiocarcinoma:Experience from 11 cases within 17 years

BACKGROUND Intrahepatic sarcomatoid chonalgiocarcinoma(s-CCC) is an extremely rare disease, accounting for less than 1% of hepatobiliary system malignancies, and its pathophysiology is not well known. On the hypothesis that its clinical, serologic,or radiologic diagnosis are not fully understood and its prognosis is poor, we investigated the distinguishing features of s-CCC compared with those of intrahepatic bile duct adenocarcinoma [cholangiocellular carcinoma(CCC)] in patients from a single center.AIM To analyze the clinical, serologic, imaging, and histopathologic characteristics of intrahepatic s-CCC patients diagnosed in a single center.METHODS The clinical, serologic, imaging, and histopathologic features of 227 patients diagnosed with intrahepatic cholangiocarcinoma(IHCC) in a single medical center during the last 17 years were analyzed. The characteristics of 11 patients with s-CCC were compared with those of 216 patients with CCC.RESULTS The number of patients with s-CCC who presented fever and abdominal pain and past history of chronic viral hepatitis or liver cirrhosis(LC) was higher than that of patients with CCC. In imaging studies, patients with s-CCC showed relatively aggressive features. However, no clear distinction was observed between s-CCC and CCC based on other clinical, serologic or radiologic examination results. An accurate diagnosis could be made only via a histopathologic examination through immunohistochemical staining. The clinical course of s-CCC was generally aggressive, and patients had a relatively poor prognosis.CONCLUSION In patients with s-CCC, early diagnosis through biopsy and aggressive treatment,including surgical resection, are important.

Hepatitis B virus infection and intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(ICC)is a devastating malignant tumor arising from the peripheral intrahepatic bile duct epithelium.The incidence and mortality of ICC is markedly increasing over the past two decades worldwide,though the cause for this rise in incidence is unclear,thus intensifying the search for alternative etiological agents and pathogenetic mechanisms.Hepatolithiasis,primary sclerosing cholangitis,parasitic infection(Opisthorchis viverrini or Clonorchis sinensis),fibropolycystic liver disease,and chemical carcinogen exposure are thought to be the risk factors for ICC.Nevertheless,the majority of ICC patients do not have any of these risk factors,and none of the established risk factors can explain the recent increasing trend of ICC.Therefore,identifying other risk factors may lead to the prevention and early detection of ICC.Chronic hepatitis B virus(HBV)infection is the predominant cause of hepatocellular carcinoma in HBVendemic areas.This review discusses the evidence implicating chronic HBV infection as a likely etiology of ICC and the pathogenetic mechanisms that might be involved.

Risk factors of intrahepatic cholangiocarcinoma in patients with hepatolithiasis:a case-control study

BACKGROUND:Why 3.3% to 10% of all patients with hepatolithiasis develop intrahepatic cholangiocarcinoma (ICC) remains unknown.We carried out a hospital-based case-control study to identify risk factors for the development of ICC in patients with hepatolithiasis in China.METHODS:Eighty-seven patients with pathologically diagnosed hepatolithiasis associated with ICC and 228 with hepatolithiasis alone matched by sex,age (±2 years),hospital admittance and place of residence were interviewed during the period of 2000-2008.Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each risk factor.RESULTS:Among the patients with hepatolithiasis associated with ICC,the mean age was 57.7 years and 61.0% were female Univariate analysis showed that the significant risk factors for ICC development in hepatolithiasis were smoking,family history of cancer,appendectomy during childhood (under age 20),and duration of symptoms >10 years.In multivariate stepwise logistic regression analysis,smoking (OR=1.931,95% CI:1.000-3.731),family history of cancer (OR=5.175,95% CI:1.216-22.022),and duration of symptoms >10 years (OR=2.348 95% CI:1.394-3.952) were independent factors.CONCLUSION:Smoking,family history of cancer and duration of symptoms >10 years may be risk factors for ICC in patients with hepatolithiasis.

Effect of contrast-enhanced ultrasound on differential diagnosis of intrahepatic cholangiocarcinoma and arterial phase enhanced hepatic inflammatory lesions

Objective: To investigate differential diagnosis between intrahepatic cholangiocarcinoma (ICC) and arterial phase enhanced hepatic inflammatory lesions in patients without liver cirrhosis using contrast-enhanced ultrasound (CEUS). Methods: ICC and hepatic inflammatory lesions cases with CEUS and pathological diagnosis between Sep 2013 and Oct 2016 were investigated retrospectively. Imaging features of conventional ultrasound and CEUS were analyzed. The parameters of time intensity curve (TIC), including the arrival time, peak intensity (PI) in the lesions, the starting time for washout, and the intensity difference at 3 min (Delta I-3) after contrast agent infection between the lesion and the liver parenchyma, were compared between ICC and hepatic inflammatory lesions. Results: Twenty-five ICC and fifteen inflammatory patients were included in this study. Seventeen ICC (68.0%) and two inflammatory cases (13.3%) showed bile duct dilatation on conventional ultrasound. Using CEUS, three ICC cases (12.0%) were misdiagnosed as inflammatory lesions and three inflammatory lesions (20.0%) as ICC; two ICC (8.0%) and one inflammatory case (6.7%) could not be made definite diagnosis. Washout started at 34.5 +/- 3.5 s and 61.5 +/- 12.9 s for ICC and inflammatory lesions respectively (P < 0.001). The intensity difference between lesion and liver parenchyma at 3 min after contrast agent injection was 10.8 +/- 3.1 dB in ICC and 4.2 +/- 2.3 dB in inflammatory group (P < 0.001). The sensitivity and specificity differentiating ICC and inflammatory lesions were 76% and 87% if the cut-off value of the intensity difference was 7.7 dB. Conclusions: Combined with TIC analysis, and particularly with the characteristic of the early-starting and obvious washout in ICC, CEUS can be useful in differential diagnosis between hepatic inflammatory lesions and ICC.

Expression of HBx protein in hepatitis B virus-infected intrahepatic cholangiocarcinoma

BACKGROUND: Hepatitis B virus (HBV) is an etiological factor of intrahepatic cholangiocarcinoma (ICC), but the pathogenic mechanisms remain unclear. This study aimed to investigate the expression and possible role of HBx, an HBV- encoded potentially oncogenic protein, in HBV-infected ICC. METHODS: Tissue samples were obtained from 54 specimens of HBV-infected ICC. Forty-four specimens were of peripheral type and 10 hilar type. Formalin-fixed, paraffin-embedded sections of the specimens were immunohistochemically stained for HBx and p53. RESULTS: HBx expression was found in 70.4% (38/54) of the specimens, and it was more frequently seen in the peripheral type than in the hilar type (79.5% vs 30.0%, P=0.002). All three well-differentiated ICCs expressed HBx, whereas 76.9% (30/39) moderately-differentiated and 41.7% (5/12) poorly-differentiated ICCs had HBx expression (P=0.033). Patients with HBx expression had a significantly higher prevalence of elevated serum alpha-fetoprotein (P=0.033). p53 protein expression was found in 18 of 54 cases (33.3%), and was not correlated with that of HBx. CONCLUSIONS: HBx may contribute to the pathogenesis of ICC, particularly the peripheral type. p53 abnormality may not play a significant role in HBx-mediated oncogenicity during ICC carcinogenesis.

Low expression of ARID1A correlates with poor prognosis in intrahepatic cholangiocarcinoma

AIM: To investigate the relationship between ARID1 A expression and clinicopathologic parameters, as well as its prognostic value, for patients with intrahepatic cholangiocarcinoma(IHCC).METHODS: We assessed ARID1 A protein and m RNA expression in IHCC tissues and paracarcinomatous(PC) tissues from 57 patients with IHCC using western blot and quantitative real-time reverse transcription polymerase chain reaction, respectively. We used Fisher's exact and χ2 tests to analyze relationships between clinicopathological parameters and ARID1 A expression. The Kaplan-Meier method and Cox regression were used to analyze survival.RESULTS: The mean ARID1 A protein level in IHCC tissues was 1.16 ± 0.36 relative units(RU), which was significantly lower than that in PC tissues(1.26 ± 0.21 RU, P < 0.01) and NL tissues(1.11 ± 0.31, P < 0.001).The mean ARID1 A m RNA level in IHCC tissues(1.20 ± 0.18) was also lower than that in PC tissues(1.27 ± 0.15, P < 0.001) and normal liver tissues(1.15 ± 0.34, P < 0.001). Low ARID1 A expression was significantly associated with tumor nodules, vein invasion, and recurrence. Median overall survival(OS) and disease-free survival(DFS) for the low ARID1 A expression group was 15.0 and 7.0 mo, respectively, which were significantly shorter than those for the high ARID1 A expression group at 25.0 and 22.0 mo(OS: P < 0.01; DFS: P < 0.001), respectively. Low ARID1 A expression was significantly associated with worse OS(HR = 3.967, 95%CI: 1.299-12.118, P = 0.016) in multivariate analyses.CONCLUSION: Low expression of ARID1 A is associated with poor prognosis in patients with IHCC, and thus may be a potential prognostic biomarker candidate in IHCC.

Radiofrequency Ablation for Postoperative Recurrences of Intrahepatic Cholangiocarcinoma

Objective: Most recurrent intrahepatic cholangiocarcinoma (RICC) lost the opportunity of radical resection while most nonsurgical management failed to prolong patients’ survival. The efficacy and safety of radiofrequency ablation (RFA) as a local treatment for recurrent hepatocellular carcinoma have been confirmed by many clinical studies. The purpose of this study was to evaluate the efficacy, long-term survival and complications of RFA for RICC. Methods: A total of 12 patients with 19 RICCs after radical resection were included in this study. The tumors were 1.9–6.8 cm at the maximum diameter (median, 3.2±1.6 cm). All patients were treated with ultrasound guided RFA. There were two RFA approaches including percutaneous and open. Results: A total of 18 RFA treatment sessions were performed. Ablation was successful (evaluated by 1-month CT after the initial RFA procedure) in 18 (94.7%) of 19 tumors. By a median follow-up period of 29.9 months after RFA, 5 patients received repeated RFA because of intrahepatic lesion recurrence. The median local recurrence-free survival period and median event-free survival period after RFA were 21.0 months and 13.0 months, respectively. The median overall survival was 30 months, and the 1- and 3-year survival rates were 87.5% and 37.5%, respectively. The complication rate was 5.6% (1/18 sessions). The only one major complication was pleural effusion requiring thoracentesis. Conclusion: This study showed RFA may effectively and safely manage RICC with 3-year survival of 37.5%. It provides a treatment option for these RICC patients who lost chance for surgery.