Molecular Detection of FGFR2 Rearrangements in Resected Intrahepatic Cholangiocarcinomas:FISH Could Be An Ideal Method in Patients with Histological Small Duct Subtype

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a subtype of primary liver cancer for which effective therapeutic agents are lacking.Fibroblast growth factor receptor 2(FGFR2)has become a promising therapeutic target in ICC;however,its incidence and optimum testing method have not been fully assessed.This study investigated the rearrangement of FGFR2 in intrahepatic cholangiocarcinoma using multiple molecular detection methods.Methods:The samples and clinical data of 167 patients who underwent surgical resection of intrahepatic cholangiocarcinoma in Zhongshan hospital,Fudan university were collected.The presence of FGFR2 gene rearrangement was confirmed using fluorescence in situ hybridization(FISH)and targeted next-generation sequencing(NGS).FGFR2 protein expression was determined using immunohistochemistry(IHC).The concordance between the methods was statistically compared.PD-L1 expression was also assessed in this cohort.The clinicopathological characteristics and genomic profile related to FGFR2 rearrangements were also analyzed to assist candidatescreening for targeted therapies.Results:FGFR2 rearrangement was detected in 21 of the 167 ICC cases(12.5%)using FISH.NGS analysis revealed that FGFR2 rearrangement was present in 16 of the 20 FISH-positive cases,which was consistent with the FISH results(kappa value=0.696,p<0.01).IHC showed that 80 of the 167 cases(48%)were positive for FGFR2 expression,which was discordant with both FISH and NGS results.By comparison,FGFR2-positivity tended to correlate with unique clinicopathological subgroups,featuring early clinical stage,histologically small duct subtype,and reduced mucus production(P<0.05),with improved overall survival(p<0.05).FGFR2-positivity was not associated with PD-L1 expression in ICCs.In genome research,we identified eight partner genes fused with FGFR2,among which FGFR2-BICC1 was the most common fusion type.BAP1,CDKN2A,and CDKN2B were the most common concomitant genetic alterations of FGFR2,whereas KRAS and IDH1 mutations were mutually exclusive to FGFR2 rearrangements.Conclusions:FISH achieved satisfactory concordance with NGS,has potential value for FGFR2 screening for targeted therapies.FGFR2 detection should be prioritized for unique clinical subgroups in ICC,which features a histological small duct subtype,early clinical stage,and reduced mucus production.

Overexpression of proteasome 26S subunit non-ATPase 6 protein and its clinicopathological significance in intrahepatic cholangiocarcinoma

BACKGROUND Currently,intrahepatic cholangiocarcinoma(ICC)poses a continuing,significant health challenge,but the relationship has yet to be established between ICC and the proteasome 26S subunit non-ATPase 6(PSMD6).AIM To investigate the protein expression and clinicopathological significance of PSMD6 in ICC.METHODS The potential impact of the PSMD6 gene on the growth of ICC cell lines was analyzed using clustered regularly interspaced short palindromic repeat knockout screening technology.Forty-two paired specimens of ICC and adjacent noncancerous tissues were collected.PSMD6 protein expression was determined by immunohistochemistry.Receiver operating characteristic curve analysis was performed to validate PSMD6 expression level,and its association with ICC patients’various clinicopathological characteristics was investigated.RESULTS The PSMD6 gene was found to be essential for the growth of ICC cell lines.PSMD6 protein was significantly overexpressed in ICC tissues(P<0.001),but showed no significant association with patient age,gender,pathological grade,or tumor-node-metastasis stage(P>0.05).CONCLUSION PSMD6 can promote the growth of ICC cells,thus playing a pro-oncogenic role.

Establishing prognostic models for intrahepatic cholangiocarcinoma based on immune cells

BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a malignant liver tumor that is challenging to treat and manage and current prognostic models for the disease are inefficient or ineffective.Tumor-associated immune cells are critical for tumor development and progression.The main goal of this study was to establish models based on tumor-associated immune cells for predicting the overall survival of patients undergoing surgery for ICC.AIM To establish 1-year and 3-year prognostic models for ICC after surgical resection.METHODS Immunohistochemical staining was performed for CD4,CD8,CD20,pan-cytokeratin(CK),and CD68 in tumors and paired adjacent tissues from 141 patients with ICC who underwent curative surgery.Selection of variables was based on regression diagnostic procedures and goodness-of-fit tests(PH assumption).Clinical parameters and pathological diagnoses,combined with the distribution of immune cells in tumors and paired adjacent tissues,were utilized to establish 1-and 3-year prognostic models.RESULTS This is an important application of immune cells in the tumor microenvironment.CD4,CD8,CD20,and CK were included in the establishment of our prognostic model by stepwise selection,whereas CD68 was not significantly associated with the prognosis of ICC.By integrating clinical data associated with ICC,distinct prognostic models were derived for 1-and 3-year survival outcomes using variable selection.The 1-year prediction model yielded a C-index of 0.7695%confidence interval(95%CI):0.65-0.87 and the 3-year prediction model produced a C-index of 0.69(95%CI:0.65-0.73).Internal validation yielded a C-index of 0.761(95%CI:0.669-0.853)for the 1-year model and 0.693(95%CI:0.642-0.744)for the 3-year model.CONCLUSION We developed Cox regression models for 1-year and 3-year survival predictions of patients with ICC who underwent resection,which has positive implications for establishing a more comprehensive prognostic model for ICC based on tumor immune microenvironment and immune cell changes in the future.

Conversion surgery after gemcitabine and cisplatin plus durvalumab for advanced intrahepatic cholangiocarcinoma:A case report

BACKGROUND The combination of immune checkpoint inhibitors and chemotherapy has shown promising results for the treatment of advanced biliary tract cancer(BTC).Based on the results of the TOPAZ-1 trial,a gemcitabine and cisplatin plus durvalumab(GCD)regimen was recently approved as first-line therapy for patients with advanced BTC.However,post-GCD conversion surgery has not been previously studied.Herein,we describe a case of advanced intrahepatic cholangiocarcinoma(ICC)successfully treated with radical surgery after GCD.CASE SUMMARY A 65-year-old female diagnosed with advanced ICC with periductal infiltration into the hepatic hilum underwent eight cycles of GCD,followed by durvalumab maintenance treatment,with mild adverse events.Partial response was obtained.Subsequently,a conversion surgery with extended left hepatectomy and bile duct resection was performed.The resection margins were negative,and the pathological diagnosis was compatible with small duct type ICC.The patient remained disease-free for 8 months without adjuvant chemotherapy.CONCLUSION We describe the case of a patient who received successful conversion surgery after GCD treatment for advanced ICC.

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.

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.

Risk factors for intrahepatic cholangiocarcinoma:A case-control study in China

AIM: To carry out a hospital-based case-control study to investigate risk factors for intrahepatic cholangiocarcinoma (ICC) in China. METHODS: A total of 312 ICC cases and 438 matched controls were included in the study. The presence of diabetes mellitus,hypertention,hepatolithiasis,primary sclerosing cholangitis,liver fluke infection (Clonorchis sinensis ),was investigated through clinical records. Blood from all participants was tested for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies. Odds ratios (OR) and 95% confi dence intervals (95% CI) were estimated using conditional logistic regression. RESULTS: Compared with controls,ICC patients had a higher prevalence of HBsAg seropositivity (48.4% vs 9.6%,P < 0.000),and hepatolithiasis (5.4% vs 1.1%,P = 0.001). By multivariate analysis,the signif icant risk factors for development of ICC were HBsAg seropositivity (adjusted OR,8.876,95% CI,5.973-13.192),and hepatolithiasis (adjusted OR,5.765,95% CI,1.972-16.851). The prevalence of anti-HCV seropositivity,diabetes mellitus,hypertention,cigarette smoking,and alcohol consumption were not significantly different between cases and controls. CONCLUSION: These findings suggest that HBV infection and hepatolithiasis are strong risk factors for development of ICC in China.

Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma

AIM:To understand the clinicopathological characteristics and treatment selections and improve survival and provide valuable information for patients with intrahepatic cholangiocarcinoma(ICC). METHODS:We retrospectively evaluated 5311 liver cancer patients who received resection between October 1999 and December 2003.Of these,429(8.1%)patients were diagnosed with ICC,and their clinicopathological, surgical,and survival characteristics were analyzed. RESULTS:Upper abdominal discomfort or pain(65.0%), no symptoms(12.1%),and hypodynamia(8.2%)were the major causes for medical attention.Laboratory tests showed 198(46.4%)patients were HBsAg positive, 90(21.3%)hadα-fetoprotein>20μg/L,50(11.9%) carcinoembryonic antigen>10μg/L,and 242(57.5%) carbohydrate antigen 19-9(CA19-9)>37 U/mL.Survival data was available for 329(76.7%)patients and their mean survival time was 12.4 mo.The overall survival of the patients with R0,R1 resection and punching exploration were 18.3,6.6 and 5.6 mo,respectively. Additionally,CA19-9>37 U/mL was associated with lymph node metastases,but inversely associated withcirrhosis.Multivariate analysis indicated that radical resection,lymph node metastases,macroscopic tumor thrombi and size,and CA19-9 were associated with prognosis. CONCLUSION:Surgical radical resection is still the most effective means to cure ICC.Certain laboratory tests(such as CA19-9)can effectively predict the survival of the patients with ICC.

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 too. 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 dinicopathological characteristics, prognostic factors and outcomes after surgical resection.

Clinicopathologic characteristics of intrahepatic cholangiocarcinoma in patients with positive serum a-fetoprotein

AIM:To explore clinicopathologic characteristics of intrahepatic cholangiocarcinoma (ICC) in patients with positive serum a-fetoprotein (AFP). METHODS:One hundred and thirty one patients who underwent surgical dissection for pathologically confirmed ICC were divided into a positive AFP (> 20 ng/mL) group (n = 32) and a negative AFP group (n = 99), whose clinicopathologic features were analyzed and compared. RESULTS:The positive rate of HBsAg and liver cirrhosis of the positive AFP group was higher than that of the negative AFP group, while the positive rate of CA19-9 (> 37 U/mL) and the lymph node metastasis rate was lower. CONCLUSION:ICC patients with positive AFP share many clinicopathologic similarities with hepatocellular carcinoma.

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.

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.

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.

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.

Can contrast enhanced ultrasound differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma?

BACKGROUND Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(ICC)differ in treatment and prognosis,warranting an effective differential diagnosis between them.The LR-M category in the contrast-enhanced ultrasound(CEUS)liver imaging reporting and data system(LI-RADS)was set up for lesions that are malignant but not specific to HCC.However,a substantial number of HCC cases in this category elevated the diagnostic challenge.AIM To investigate the possibility and efficacy of differentiating ICC from HCC classified in the LR-M category according to the CEUS LI-RADS.METHODS Patients with complete CEUS records together with pathologically confirmed ICC and LR-M HCC(HCC classified in the CEUS LI-RADS LR-M category)between January 2015 and October 2018 were included in this retrospective study.Each ICC was assigned a category as per the CEUS LI-RADS.The enhancement pattern,washout timing,and washout degree between the ICC and LR-M HCC were compared using theχ2 test.Logistic regression analysis was used for prediction of ICC.Receiver operating characteristic(ROC)curve analysis was used to investigate the possibility of LR-M criteria and serum tumor markers in differentiating ICC from LR-M HCC.RESULTS A total of 228 nodules(99 ICCs and 129 LR-M HCCs)in 228 patients were included.The mean sizes of ICC and LR-M HCC were 6.3±2.8 cm and 5.5±3.5 cm,respectively(P=0.03).Peripheral rim-like arterial phase hyperenhancement(APHE)was detected in 50.5%(50/99)of ICCs vs 16.3%(21/129)of LR-M HCCs(P<0.001).Early washout was found in 93.4%(93/99)of ICCs vs 96.1%(124/129)of LR-M HCCs(P>0.05).Marked washout was observed in 23.2%(23/99)of ICCs and 7.8%(10/129)of LR-M HCCs(P=0.002),while this feature did not show up alone either in ICC or LR-M HCC.Homogeneous hyperenhancement was detected in 15.2%(15/99)of ICCs and 37.2%(48/129)of LR-M HCCs(P<0.001).The logistic regression showed that rim APHE,carbohydrate antigen 19-9(CA 19-9),and alpha fetoprotein(AFP)had significant correlations with ICC(r=1.251,3.074,and-2.767,respectively;P<0.01).Rim APHE presented the best enhancement pattern for diagnosing ICC,with an area under the ROC curve(AUC)of 0.70,sensitivity of 70.4%,and specificity of 68.8%.When rim hyperenhancement was coupled with elevated CA 19-9 and normal AFP,the AUC and sensitivity improved to 0.82 and 100%,respectively,with specificity decreasing to 63.9%.CONCLUSION Rim APHE is a key predictor for differentiating ICC from LR-M HCC.Rim APHE plus elevated CA 19-9 and normal AFP is a strong predictor of ICC rather than LR-M HCC.Early washout and marked washout have limited value for the differentiation between the two entities.

Current status of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a rare primary liver cancer with a global increasing trend in recent years. Symptoms tend to be vague and insidious in development, often are diagnosed at an advanced stage when only palliative approaches can be used with a median survival rate of months. Comparing with HCC, ICC tends to spread to lymph nodes early, and is rarely limited to the regional lymph nodes, with a frequent postoperative recurrence. Surgery is the only choice of curative therapy for ICC, but recently no consensus has been established for operation. Thus, more data from multiple centers and more cases are needed. Generally speaking, current adjunctive therapy cannot clearly improve survival. Further research is needed to find more effective radio- and chemotherapeutic regimens.

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.

Sarcomatoid intrahepatic cholangiocarcinoma mimicking liver abscess: A case report

BACKGROUND Sarcomatoid intrahepatic cholangiocarcinoma(SICC) is an extremely rare and highly invasive malignant tumor of the liver. To our knowledge, the imaging findings of sarcomatous cholangiocarcinoma have been rarely reported; and radiological features of this tumor mimicking liver abscess have not yet been reported.CASE SUMMARY We present a case of SICC mimicking liver abscess. The patient, a 43-year-old male, complained of repeated upper right abdominal discomfort and intermittent distension over a period of one month. Radiology examination revealed a huge focal lesion in the right liver. The lesion was hypointense on computed tomography with honeycomb enhancement surrounded by enhanced peripheral areas. It showed a hypo-signal on non-contrast T1-weighted images and a hypersignal on non-contrast T2-weighted images. Radiologists diagnosed the lesion as an atypical liver abscess. The patient underwent a hepatectomy. After surgery, he survived another 2.5 mo before passing away. A search of Pub Med and Google revealed 43 non-repeated cases of SICC reported in 20 published studies. The following is a short review in order to improve the diagnostic and therapeutic skills in cases of SICC.CONCLUSION This report presents the clinical and radiological features of SICC and imaging features which showed hypovascularity and progressive enhancement. SICC can present as a multilocular cyst on radiological images and it is necessary to distinguish this lesion from an atypical abscess. Simple surgical treatment is not the best treatment option for this disease.

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.