Intrahepatic Cholangiocarcinoma Group Research Articles

Cost-effectiveness of ivosidenib versus chemotherapy for previously treated IDH1-mutant advanced intrahepatic cholangiocarcinoma in Taiwan

BackgroundInternational guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib’s cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV.MethodsA 3-state partitioned survival model was employed to assess ivosidenib’s cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib’s cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios.ResultsIvosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib’s cost and utility values on estimate uncertainty.ConclusionsAt NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50–60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.

Clinical Characteristics of Non-B and Non-C Biopsy-Proven Primary Liver Cancers in an HBV- Endemic Area: A Retrospective Study.

To explore the distribution of probable causes and clinical characteristics of non-B and non-C (NBNC) primary liver cancer (PLC) patients in the HBV-endemic region. A total of 86 individuals with biopsy-proven NBNC-PLC were enrolled. NBNC-PLC patients were defined as negative for both anti-HCV antibodies and five serum hepatitis B markers. Patients' characteristics were collected from medical records. Among them, most of the NBNC-PLC patients had intrahepatic cholangiocarcinoma (ICC) (81.4%), and 12.8% had hepatocellular carcinoma (HCC). The NBNC ICC group had more platelet count, GGT, and CA199 levels; approximately two-thirds were female, and it was more often present in patients with biliary inflammatory diseases, especially intrahepatic biliary lithiasis. The NBNC HCC group was older and had a higher proportion of dyslipidemia, obesity, cirrhosis, and AFP levels. Our data revealed that most of the NBNC PLC patients were ICC. Female patients with biliary inflammatory diseases and higher CA199 levels had an increased risk of ICC, and patients with metabolic risk factors and elevated AFP levels were more likely to develop HCC. Additional research should be performed to verify this finding.

Dual-phenotype hepatocellular carcinoma: correlation of MRI features with other primary hepatocellular carcinoma and differential diagnosis.

Dual-phenotype hepatocellular carcinoma (DPHCC) is a rare subtype of hepatocellular carcinoma characterized by high invasiveness and a poor prognosis. The study aimed to compare clinical and magnetic resonance imaging (MRI) features of DPHCC with that of non-DPHCC and intrahepatic cholangiocarcinoma (ICC), exploring the most valuable features for diagnosing DPHCC. A total of 208 cases of primary liver cancer, comprising 27 DPHCC, 113 non-DPHCC, and 68 ICC, who undergone gadoxetic acid-enhanced MRI, were enrolled in this study. The clinicopathologic and MRI features of all cases were summarized and analyzed. Univariate and multivariate logistic regression analyses were conducted to identify the predictors. Kaplan-Meier survival analysis was used to evaluate the 1-year and 2-year disease-free survival (DFS) and overall survival (OS) rates in the cohorts. In the multivariate analysis, the absence of tumor capsule (P = 0.046; OR = 9.777), persistent enhancement (P = 0.006; OR = 46.941), arterial rim enhancement (P = 0.011; OR = 38.211), and target sign on DWI image (P = 0.021; OR = 30.566) were identified as independently significant factors for distinguishing DPHCC from non-DPHCC. Serum alpha-fetoprotein (AFP) >20 μg/L (P = 0.036; OR = 67.097) and hepatitis B virus (HBV) positive (P = 0.020; OR = 153.633) were independent significant factors for predicting DPHCC compared to ICC. The 1-year and 2-year DFS rates for patients in the DPHCC group were 65% and 50%, respectively, whereas those for the non-DPHCC group were 80% and 60% and for the ICC group were 50% and 29%, respectively. The 1-year and 2-year OS rates for patients in the DPHCC group were 74% and 60%, respectively, whereas those for the non-DPHCC group were 87% and 70% and for the ICC group were 55% and 37%, respectively. Kaplan-Meier survival analysis revealed significant differences in the 1-year and 2-year OS rates between the DPHCC and non-DPHCC groups (P = 0.030 and 0.027) as well as between the DPHCC and ICC groups (P = 0.029 and 0.016). In multi-parameter MRI, combining the assessment of the absence of tumor capsule, persistent enhancement, arterial rim enhancement, and target sign on DWI image with clinical data such as AFP >20 μg/L and HBV status may support in the diagnosis of DPHCC and differentiation from non-DPHCC and ICC. Accurate preoperative diagnosis facilitates the selection of personalized treatment options.

Impact of Tumor Subclassifications for Identifying an Appropriate Surgical Strategy in Patients with Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is subclassified into small and large duct types. The impact of these subclassifications for identifying appropriate surgical strategies remains unclear. This study included 118 patients with ICC who underwent liver resection. Based on the pathological examination results, the participants were divided into the small duct-type ICC group (n = 64) and large duct-type ICC group (n = 54). The clinicopathological features and postoperative outcomes were compared between the two groups to investigate the impact of subclassification for selecting appropriate surgical strategies. Ten patients in the small duct-type ICC group had synchronous or metachronous hepatocellular carcinoma. The large duct-type ICC group had higher proportions of patients who underwent major hepatectomy, extrahepatic bile duct resection, portal vein resection, and lymph node sampling or dissection than the small duct-type ICC group. The large duct-type ICC group had significantly higher incidences of lymph node metastasis/recurrence and pathological major vessel invasion than the other. The small duct-type ICC group exhibited significantly higher recurrence-free and overall survival rates than the large duct-type ICC group. Further, the large duct-type ICC group had a significantly higher incidence of lymph node metastasis/recurrence than the small duct-type ICC at the perihilar region group. Suitable surgical strategies may differ between the small and large duct-type ICCs. In patients with large duct-type ICCs, hepatectomy with lymph node dissection and/or biliary reconstruction should be considered, whereas hepatectomy without these advanced procedures can be suggested for patients with small duct-type ICCs.

Ultrasound findings of hepatic epithelioid hemangioendothelioma: comparison with other malignant hepatic tumors.

To investigate and compare the ultrasonic features of hepatic epithelioid hemangioendothelioma (HEHE) and other common hepatic malignancies, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepatic metastatic tumor (HMT). A total of 37 patients with pathologically proven HEHE, 37 HCC cases, 37 ICC cases, and 37 HMT cases were enrolled from single hospital. The clinical characteristics and ultrasonic features of all cases were summarized and statistically analyzed. There were significant differences in sex and age between the HEHE group and other three groups (P < 0.001). The probability of HEHE infection with hepatitis B virus was lower than that of HCC and ICC groups (P < 0.05). The probability of elevated serum tumor markers in HEHE was significantly lower than that in the other three groups (P < 0.05). On conventional ultrasound (CUS), the probability of multiple lesions in HEHE was significantly higher than that in the other three groups (P < 0.05). On contrast-enhanced ultrasound (CEUS), the time to wash out in HEHE was significantly shorter than that of the other three groups (P < 0.001). The proportion of synchronous or slow enhancement in HEHE was significantly higher than that of the other three groups (P < 0.001). The proportion of HEHE with iso- or hypo-enhancement was significantly higher than in HCC and HMT groups (P < 0.05). HEHE mainly performed multiple hypoechoic lesions on CUS and displayed greater odds of synchronous enhancement in arterial phase, iso- or hypo-enhancement in peak time and wash out more quickly on CEUS, which allowed for differentiation from other common malignant tumors.

Diagnostic Value of MRI Features in Dual-phenotype Hepatocellular Carcinoma: A Preliminary Study

This study aimed to explore the magnetic resonance imaging (MRI) features of dual-phenotype hepatocellular carcinoma (DPHCC) and their diagnostic value.The data of 208 patients with primary liver cancer were retrospectively analysed between January 2016 and June 2021. Based on the pathological diagnostic criteria, 27 patients were classified into the DPHCC group, 113 patients into the noncholangiocyte-phenotype hepatocellular carcinoma (NCPHCC) group, and 68 patients with intrahepatic cholangiocarcinoma (ICC) were classified into the ICC group. Two abdominal radiologists reviewed the preoperative MRI features by a double-blind method. The MRI features and key laboratory and clinical indicators were compared between the groups. The potentially valuable MRI features and key laboratory and clinical characteristics for predicting DPHCC were identified by univariate and multivariate analyses, and the odds ratios (ORs) were recorded. In multivariate analysis, tumour without capsule (P = 0.046, OR = 9.777), dynamic persistent enhancement (P = 0.006, OR = 46.941), and targetoid appearance on diffusion-weighted imaging (DWI) (P = 0.021, OR = 30.566) were independently significant factors in the detection of DPHCC compared to NCPHCC. Serum alpha-fetoprotein (AFP) > 20 µg/L (P = 0.036, OR = 67.097) and prevalence of hepatitis B virus (HBV) infection (P = 0.020, OR = 153.633) were independent significant factors in predicting DPHCC compared to ICC. The differences in other tumour marker levels and imaging features between the groups were not significant. In MR enhanced and diffusion imaging, tumour without capsule, persistent enhancement and DWI targetoid findings, combined with AFP > 20 µg/L and HBV infection-positive laboratory results, can help to diagnose DPHCC and differentiate it from NCPHCC and ICC. These results suggest that clinical, laboratory and MRI features should be integrated to construct an AI diagnostic model for DPHCC.

Applications of Dynamic Contrast-Enhanced Ultrasound in Differential Diagnosis of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma in Non-cirrhotic Liver.

The aim of the work described here was to investigate the value of dynamic contrast enhanced ultrasound (DCE-US) and quantitative analysis in pre-operative differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) in non-cirrhotic liver. In this retrospective study, patients with histopathologically proven ICC and HCC lesions in non-cirrhotic liver were included. All patients underwent contrast-enhanced ultrasound (CEUS) examinations with an Acuson Sequoia unit (Siemens Healthineers, Mountain View, CA, USA) unit or LOGIQ E20 (GE Healthcare, Milwaukee, WI, USA) within 1 wk before surgery. SonoVue (Bracco, Milan, Italy) was used as the contrast agent. B-mode ultrasound (BMUS) features and CEUS enhancement patterns were analyzed. DCE-US analysis was performed by VueBox software (Bracco). Two regions of interest (ROIs) were set in the center of the focal liver lesions and their surrounding liver parenchyma. Time-intensity curves (TICs) were generated, and quantitative perfusion parameters were obtained and compared between the ICC and HCC groups using the Student t-test or Mann-Whitney U-test. From November 2020 to February 2022, patients with histopathologically confirmed ICC (n=30) and HCC (n=24) lesions in non-cirrhotic liver were included. During the arterial phase (AP) of CEUS, ICC lesions exhibited heterogeneous hyperenhancement (13/30, 43.3%), heterogeneous hypo-enhancement (2/30, 6.7 %) and rim-like hyperenhancement (15/30, 50.0%), whereas all HCC lesions exhibited heterogeneous hyperenhancement (24/24, 100.0%) (p < 0.05). Subsequently, most of the ICC lesions exhibited AP wash-out (83.3%, 25/30), whereas a few cases exhibited wash-out in the portal venous phase (PVP) (15.7%, 5/30). In contrast, HCC lesions exhibited AP wash-out (41.7%, 10/24), PVP wash-out (41.7%, 10/24) and a small part of late phase wash-out (16.7%, 4/24) (p < 0.05). Compared with those of HCC lesions, TICs of ICCs revealed earlier and lower enhancement during the AP, faster decline during the PVP and reduced area under the curve. The combined area under the receiver operating characteristic curve (AUROC) of all significant parameters was 0.946, with 86.7% sensitivity, 95.8% specificity and 90.7% accuracy in differential diagnosis between ICC and HCC lesions in non-cirrhotic liver, which improved the diagnostic efficacy of CEUS (58.3% sensitivity, 90.0% specificity and 75.9% accuracy). ICC and HCC lesions in non-cirrhotic liver might exhibit some overlap of CEUS features in diagnosis. DCE-US with quantitative analysis would be helpful in pre-operative differential diagnosis.

Extracellular volume fraction using contrast-enhanced CT is useful in differentiating intrahepatic cholangiocellular carcinoma from hepatocellular carcinoma.

To evaluate whether tumor extracellular volume fraction (fECV) on contrast-enhanced computed tomography (CT) aids in the differentiation between intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). In this retrospective study, 113 patients with pathologically confirmed ICC (n = 39) or HCC (n = 74) who had undergone preoperative contrast-enhanced CT were enrolled. Enhancement values of the tumor (Etumor) and aorta (Eaorta) were obtained in the precontrast and equilibrium phase CT images. fECV was calculated using the following equation: fECV [%] = Etumor/Eaorta × (100 - hematocrit [%]). fECV values were compared between the ICC and HCC groups using Welch's t-test. The diagnostic performance of fECV for differentiating ICC and HCC was assessed using receiver-operating characteristic (ROC) analysis. fECV and the CT imaging features of tumors were evaluated by two radiologists. Multivariate logistic regression analysis was performed to identify factors predicting a diagnosis of ICC. Mean fECV was significantly higher in ICCs (43.8% ± 13.2%) than that in HCCs (31.6% ± 9.0%, p < 0.001). The area under the curve for differentiating ICC from HCC was 0.763 when the cutoff value of fECV was 41.5%. The multivariate analysis identified fECV (unit OR: 1.10; 95% CI: 1.01-1.21; p < 0.05), peripheral rim enhancement during the arterial phase (OR: 17.0; 95% CI: 1.29-225; p < 0.05), and absence of washout pattern (OR: 235; 95% CI: 14.03-3933; p < 0.001) as independent CT features for differentiating between the two tumor types. A high value of fECV, peripheral rim enhancement during the arterial phase, and absence of washout pattern were independent factors in the differentiation of ICC from HCC.

18F-FDG PET/CT radiomic analysis for classifying and predicting microvascular invasion in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

BackgroundMicrovascular invasion (MVI) is a critical risk factor for early recurrence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to explore the contribution of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomic features for the preoperative prediction of HCC and ICC classification and MVI.MethodsIn this retrospective study, 127 (HCC: ICC =76:51) patients with suspected MVI accompanied by either HCC or ICC were included (In HCC group, MVI positive: negative =46:30 in ICC group, MVI positive: negative =31:20). Results-driven feature engineering workflow was used to select the most predictive feature combinations. The prediction model was based on supervised machine learning classifier. Ten-fold cross validation on training cohort and independent test cohort were constructed to ensure stability and generalization ability of models.ResultsFor HCC and ICC classification, radiomics predictors composed of two PET and one CT feature achieved area under the curve (AUC) of 0.86 (accuracy, sensitivity, specificity was 0.82, 0.78, 0.88, respectively) on test cohort. For MVI prediction, in HCC group, our MVI prediction model achieved AUC of 0.88 (accuracy, sensitivity, specificity was 0.78, 0.88, 0.60 respectively) with three PET features associated with tumor stage on test cohort. In ICC group, the phenotype composed of two PET features and carbohydrate antigen 19-9 (CA19-9) achieved AUC of 0.90 (accuracy, sensitivity, specificity was 0.77, 0.75, 0.80, respectively).Conclusions18F-FDG PET/CT radiomic features integrating clinical factors have potential in HCC and ICC classification and MVI prediction, while PET features have dominant predictive power in model performance. The prediction model has value in providing a non-invasive biomarker for an earlier indication and comprehensive quantification of primary liver cancers.

Results of Intrahepatic Cholangiocarcinoma Resections: a Single-Center Analysis.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary neoplasm of the liver after hepatocellular carcinoma (HCC). Although an underlying cause is not usually found, liver flukes, cirrhosis, primary sclerosing cholangitis, and viral hepatitis have been found to increase the risk in recent years. In this study, we aimed to present our experience on ICC and compare the outcomes of patients with a concomitant liver pathology and with incidentally detected ICC. Thirty-three patients who underwent surgical resection for ICC were included in the study. Patients were divided into two groups, group one (with concomitant liver disease, n = 13) and group two (incidentally detected ICC, n = 18). Demographics, perioperative findings, pathological properties, recurrence rates, and survival rates were retrospectively analyzed and compared between the groups. The mean age of patients was 59.77 ± 9.81years, of whom sixteen (51.6%) were males. Thirteen patients (41.9%) had concomitant liver disease, the most common being chronic hepatitis B infection. Eighteen patients (58.1%) had incidentally detected ICC. There were no significant differences between the groups except for follow-up time and recurrence rate. The recurrence rate was significantly higher in the incidentally detected ICC group (61.1% versus 7.7%, p = 0.003). Follow-up time was significantly higher in patients with concomitant liver disease (42 versus 17.5months, p = 0.007). The mortality rate was higher in the incidentally detected ICC group (55.6 to 23.1%, p = 0.071) but the difference did not reach statistical significance. Surgical resection in ICC patients with underlying liver disease is associated with better prognosis than in incidentally detected ICC patients. Incidental ICC may be a different tumor with different biology, hence the high recurrence rates.

Strategy for Discriminating Intraductal Papillary Neoplasm of the Bile Duct (IPNB) in Different Anatomical Locations Based on Clinicopathological Features and Outcomes

Introduction: In the statement by the Japan-Korea expert pathologists, it was described that Intraductal papillary neoplasm of bile duct (IPNB) can be subclassified into two types. Each of these two types has a different tendency in the anatomical location and invasiveness. The present study assessed the clinical features and outcomes of intra-/extra- hepatic IPNB to establish optimal therapeutic strategies for IPNB. Method: The present study included 28 cases who were pathologically diagnosed with IPNB. These cases were classified by the anatomical location where it arises (intrahepatic-IPNB 7 cases/ extrahepatic-IPNB 21 cases). Furthermore, we attempted to further clarify the characteristics of intrahepatic IPNB by comparing with intrahepatic cholangiocarcinoma (ICC). Results: Superficial extension was significantly more frequent in extrahepatic type with 17 cases (p=0.003). Pathologically, lymphatic invasion was significantly more frequent in the extrahepatic type (p=0.033), and mucus production tended to be more frequent in intrahepatic type (p=0.063). In terms of prognosis, recurrence was observed in 9 cases of extrahepatic type. As compared with 26 cases of ICC, preoperative intrahepatic (p=0.026) and extrahepatic (p<0.01) biliary dilatation and histological mucus production (p<0.01) were significantly found in primary hepatic IPNB. ICC group significantly showed CA19-9 >100 (p=0.043), portal invasion (p<0.01) and recurrence (p<0.01). Conclusions: Preoperative diagnosis of intrahepatic IPNB is possible because of the relatively common and characteristic imaging findings. However, considering the malignant potential in patients with high tumor markers and portal vein invasion, as well as the characteristics of horizontal extension of IPNB, systematic hepatectomy with adequate bile duct resection are recommended.

Diagnostic performance of apparent diffusion coefficient values for the differentiation of intrahepatic cholangiocarcinoma from gastrointestinal adenocarcinoma liver metastases.

BackgroundWe aimed to investigate whether there is a difference between intrahepatic cholangiocarcinoma (IHCC) and liver metastases of gastrointestinal system (GIS) adenocarcinoma in terms of apparent diffusion coefficient (ADC) values.Patients and methodsFrom January 2018 to January 2020, we retrospectively examined 64 consecutive patients with liver metastases due to gastrointestinal system adenocarcinomas and 13 consecutive IHCC in our hospital’s medical records. After exclusions, fifty-three patients with 53 liver metastases and 10 IHCC were included in our study. We divided the patients into two groups as IHCC and liver metastases of GIS adenocarcinoma. For mean apparent diffusion coefficient (ADCmean) values, the region of interests (ROI) was placed in solid portions of the lesions. ADCmean values of groups were compared.ResultsThe mean age of IHCC group was 62.50 ± 13.49 and mean age of metastases group was 61.15 ± 9.18. ADCmean values were significantly higher in the IHCC group compared to the metastatic group (p < 0.001). ROC curves method showed high diagnostic accuracy (AUC = 0.879) with cut-off value of < 1178 x 10-6 mm2/s for ADCmean (Sensitivity = 90.57, Specificity = 70.0, positive predictive value [PPV] = 94.1, negative predictive value [NPV] = 58.3) in differentiating adenocarcinoma metastases from IHCC.ConclusionsThe present study results suggest that ADC values have a potential role for differentiation between IHCC and GIS adenocarcinoma liver metastases which may be valuable for patient management.

Proteomic analysis of serum and serum exosomes, and their application in intrahepatic cholangiocarcinoma

外泌体是由各种类型细胞在正常或非正常生理情况下分泌释放至细胞外且携带多种生物活性分子的细胞外囊泡,在细胞间通讯和免疫应答等生物过程中发挥着重要作用。肝内胆管癌是一种胆道上皮恶性肿瘤,早期无明显临床症状且生存率较低,目前常用的诊断手段包括依赖于影像设备的诊断方式和灵敏度及特异性较低的诊断标志物等,这些手段的不足对发展新的特异性标志物提出了需求。该文对血清中的外泌体进行了分离和表征,并采用液相色谱-质谱技术针对健康组与肝内胆管癌患者组的血清样本和血清外泌体样本进行了无标记定量蛋白质组学分析,分别从两种类型样本中鉴定并筛选到271和430种可信蛋白质。基于血清样本和血清外泌体样本的可信蛋白质定量表达值进行多维统计分析都能将健康组与肝内胆管癌患者组良好地区分开。对血清样本中鉴定到的蛋白质进行差异蛋白质筛选,肝内胆管癌患者组相对于健康组有15个上调和8个下调蛋白质;对血清外泌体样本中鉴定到的蛋白质进行差异蛋白质筛选,肝内胆管癌患者组相对于健康组有33个上调和18个下调蛋白质;基于两种样本筛选到的差异蛋白质中仅有4个是重复的,且基于血清外泌体样本的51个差异蛋白质中有35个蛋白质属于外泌体蛋白质数据库。针对差异蛋白质进行生物学信息分析,与差异蛋白质相关的分子功能、生物过程和信号通路主要涉及天然免疫反应、炎症反应和凝血等过程。该研究为发现肝内胆管癌的潜在生物标志物和探究肝内胆管癌的发生、发展和转移等过程提供了参考和借鉴价值。此外,通过比较研究发现血清外泌体样本能够获得较多的差异蛋白质和生物学信息,证明了外泌体作为组学分析样本的价值和应用潜力。

Increased Serum Levels of Trypsin Inhibitor Kazal1 in Patients with HBV-Related Hepatocellular Carcinoma Predict a Poor Prognosis.

Trypsin Inhibitor Kazal1 (SPINK1) is overexpressed in various tumors, but its role in hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is unclear. The aim of this study was to investigate SPINK1 levels during the chronic progression of HBV infection and their association with the prognosis of HBV-related HCC. This study enrolled 102 patients with chronic hepatitis B (CHB), 95 patients with HBV-related liver cirrhosis (LC), 104 patients with HBV-related HCC, 25 patients with intrahepatic cholangiocarcinoma (ICC), and 98 healthy controls (HCs). The serum expression of SPINK1 in each group was compared. SPINK1 levels in the supernatant of HepG2.2.15, HepG2, Huh7, and LO2 cells were determined by ELISA. The diagnostic efficacy of SPINK1 for HBV-related HCC was evaluated. Hazard ratios (HRs) for the short-term prognosis of HBV-related HCC were assessed. SPINK1 levels were the highest in the HBV-related HCC group compared with the HC, CHB, HBV-related LC, and ICC groups (3.19 ± 1.11 versus 1.09 ± 0.38, 1.75 ± 0.55, 2.09 ± 0.62, and 2.40 ± 0.85 ng/mL, p < 0.01). SPINK1 levels in the supernatant of HepG2.2.15 cells were higher than those in HepG2, Huh7, and LO2 cells (2.85 ± 0.03 versus 1.54 ± 0.04, 1.50 ± 0.04, 0.9 ± 0.04 ng/mL, p < 0.001). The best cutoff point for the SPINK1 level was 2.48 ng/mL. The high SPINK1 expression group (≥ 2.48 ng/mL) had a larger tumor size, poorer Child-Pugh classification and more HBV DNA than the low expression group (< 2.48 ng/mL) (all p < 0.05). In the HBV-related HCC group, a SPINK1 level ≥ 2.48 ng/mL along with a high alpha-fetoprotein (AFP) level, large tumor size and poor Child-Pugh grade predicted poorer overall survival (HR 4.65, 95% confidence interval (CI): 2.07 - 10.43, p < 0.001). Serum SPINK1 had a high diagnostic efficacy for predicting HBV-related HCC. The presence of HBV-related HCC with a high serum SPINK1 level (≥ 2.48 ng/mL) may be associated with a poor short-term prognosis.

Intravoxel incoherent motion diffusion-weighted imaging to differentiate hepatocellular carcinoma from intrahepatic cholangiocarcinoma

The present study aimed to explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in differentiating hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC). This study included 65 patients with malignant hepatic nodules (55 with HCC, 10 with ICC), and 17 control patients with normal livers. All patients underwent IVIM-DWI scans on a 3.0 T magnetic resonance imaging (MRI) scanner. The standard apparent diffusion coefficient (ADC), pure diffusion coefficient (Dslow), pseudo-diffusion coefficient (Dfast), and perfusion fraction (f) were obtained. Differences in the parameters among the groups were analysed using one-way ANOVA, with p < 0.05 indicating statistical significance. Receiver operating characteristic (ROC) curve analysis was used to compare the efficacy of each parameter in differentiating HCC from ICC. ADC, Dslow, Dfast, f significantly differed among the three groups. ADC and Dslow were significantly lower in the HCC group than in the ICC group, while Dfast was significantly higher in the HCC group than in the ICC group; f did not significantly differ between the HCC and ICC groups. When the cut-off values of ADC, Dslow, and Dfast were 1.27 × 10−3 mm2/s, 0.81 × 10−3 mm2/s, and 26.04 × 10−3 mm2/s, respectively, their diagnostic sensitivities for differentiating HCC from ICC were 98.18%, 58.18%, and 94.55%, their diagnostic specificities were 50.00%, 80.00%, and 80.00%, and their areas under the ROC curve (AUCs) were 0.687, 0.721, and 0.896, respectively. Dfast displayed the largest AUC value. IVIM-DWI can be used to differentiate HCC from ICC.

Diagnostic value of serum glypican-3 alone and in combination with AFP as an aid in the diagnosis of liver cancer

BackgroundRecently, a series of studies have been published to examine the possible diagnostic and prognostic values of glypican-3 (GPC3) in liver cancer with conflicting results observed. Thus, the present study aimed to assess the values of preoperative serum GPC3 alone and in combination with AFP for the diagnosis of liver cancer. MethodsAn enzyme-linked immunoassay was used to quantify serum GPC3 in hepatocellular carcinoma group (HCC, n = 210), intrahepatic cholangiocarcinoma group (ICC, n = 36), combined hepatocellular cholangiocarcinoma group (cHCC-CC, n = 8), metastatic liver cancer group (MLC, n = 10) and normal controls (NC, n = 134). ResultsThe area under the curve (AUC) of GPC3 for HCC versus NC was 0.879, with a sensitivity of 79.52% at an optimal cutoff value of 0.0414 ng/mL; when GPC3 was combined with AFP, the AUC and sensitivity were increased to 0.925 and 88.10%, respectively. In addition, 43 of 68 AFP-negative patients had elevated GPC3 levels. Furthermore, the positive rate of GPC3 was significantly higher than the that of AFP for HCC in early stage. ConclusionsSerum GPC3 was superior to AFP for the diagnosis of early-stage HCC, and may be complementary to AFP for distinguishing HCC from NC.

Major hepatectomy for intrahepatic cholangiocarcinoma or colorectal liver metastases. Are we talking about the same story?

Introduction: Major hepatectomy (MH) is often needed in the curative management of intrahepatic cholangiocarcinoma (IHCC) and colorectal liver metastases (CRLM). While similar outcomes could be expected after MH for IHCC and CRLM, reported mortality and morbidity rates are worse after MH for IHCC. The lack of comprehensive analysis in the literature motivated the current study. Methods: All patients undergoing MH with curative intent for IHCC or CRLM from 2003 to 2009 were included from two dedicated multi-institutional datasets. Preoperative management and short-term outcomes after MH for IHCC or CRLM were first compared. Independent predictors of postoperative mortality and morbidity were identified. Results: Among 827 patients, 333 and 494 patients underwent MH for IHCC and CRLM, respectively. Preoperative portal vein embolization was significantly more performed in the CRLM group (p<0.001). MH in the IHCC group required more preoperative biliary drainage (p=0.001) and more extended resection (p<0.001). Postoperative mortality and severe morbidity rates were significantly higher in the IHCC group (7.2% vs. 1.2%, p< 0.001and 29.7% vs. 11.1%, p<0.001, respectively). MH for IHCC was an independent risk factor for mortality (p<0.001) and severe morbidity (p<0.001). After matching (227 patients in each group) on demographics and resection extent, differences regarding preoperative management, underlying liver and postoperative outcomes remained statistically significant. Conclusion: Mortality and morbidity were significantly higher in patients operated on for IHCC. These differences in outcomes might be related to a lack of preoperative planning underestimating the need for extended resection to the parenchyma, the vessels and the biliary tract.

2946 Does Non-Alcoholic Fatty Liver Disease Increase the Risk of Cholangiocarcinoma? A Single Center Retrospective Review

INTRODUCTION: Cholangiocarcinoma is a highly aggressive cancer of the bile duct epithelium, usually diagnosed at an advanced stage. Limited research has shown evolving risk factors and pathogenesis of cholangiocarcinoma. Studies have revealed a link between Non-Alcoholic Fatty Liver Disease (NAFLD) and cholangiocarcinoma, mainly intrahepatic cholangiocarcinoma. The major risk factors for NAFLD- include obesity, impaired fasting glucose, dyslipidemia, and metabolic syndrome. In this study, we aim to determine a possible association between NAFLD and cholangiocarcinoma. METHODS: The electronic medical records were retrospectively reviewed for adults with NAFLD, Intrahepatic cholangiocarcinoma (ICC) and Extrahepatic cholangiocarcinoma (ECC) by ICD code, imaging, or pathological report. Exclusion criteria were; alcoholic liver disease, primary sclerosing cholangitis, hepatitis B &amp; C, HIV infection, and inflammatory bowel disease between March 2012-2019. Analysis was conducted on possible risk factors such as NAFLD, metabolic syndrome and subsequent risks; diabetes mellitus, BMI, dyslipidemia, hypertension (HTN), and coronary artery disease. RESULTS: A total of 59 patients with diagnosis of cholangiocarcinoma was collected and classified into ICC (N = 48) and ECC (N = 10) with mean age of 72 years. Gender distribution was 54% females and 46% males, in ICC and 40% females vs 60% males in ECC, respectifully. 18% of patients with ICC had NAFLD in comparison with 0% in the ECC class. Fisher exact test showed 37.5% of patients with ICC had metabolic syndrome vs 30% of patients with ECC, but this was statistically not significant. Each individual risk factor for metabolic syndrome was further analyzed and among these 81% of patients with ICC had HTN and was statistically significant vs 50% of ECC cases had HTN. CONCLUSION: Our cohort did not demonstrate an association between NAFLD and cholangiocarcinoma. Our sample size was low and ICC had more representation than ECC. Diagnoses of NAFLD was obtained mainly by imaging and pathology results rather than ICD codes, but underrepresented in our study in comparison to the general population, likely from undercoding. There was no association between gender, age, metabolic syndrome or its risk factors, except HTN, which was prevalent in the ICC group with statistical significance. This finding was not seen in prior studies. This could likely represent more prevalence of HTN overall in the cohort, however more research is helpful in determining this possible association.

Combined hepatocellular-cholangiocarcinoma

Combined hepatocellular-cholangiocarcinoma (CHCC) is a rare type of primary liver cancer (PLC). The aim of this study was to investigate the disease characteristics in CHCC patients and compare them with those in hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC).The perioperative and follow-up data of CHCC patients (n = 15), HCC patients (n = 577), and ICC patients (n = 61) were retrospectively analyzed, and the clinicopathological characteristics were compared among these 3 groups.In the CHCC group, the serum level of AFP was significantly higher than that of the ICC group (P = .002), and the CA19-9 level was higher than that of the HCC group (P = .011). The positive rates of CK7 and CK19 expression were higher in CHCC group than in HCC group (both P < .001), while the positive rates of Glypican–3 and Hepatocyte expression were higher in CHCC group than in ICC group (both P < .001). Meanwhile, the CHCC patients were likely to have undergone more MJH/LT than the HCC patients (P = .037) and the ICC patients (P = .011). Macrovascular invasion and lymph node metastasis in the CHCC group were significantly higher but satellite lesions were similar, compared to the HCC group. Both the 1-year disease-free survival (DFS) and the 1-year overall survival (OS) for the CHCC patients were worse than those for the HCC patients. AFP ≥ 400 ng/ml, tumor size ≥5 cm, tumor number ≥2, macro- and microvascular invasion, distant metastasis and positive margin were risk factors for both DFS and OS for the PLC patients. Multivariate analysis also confirmed that ICC and lymph node metastasis were risk factors for DFS and MJH/LT was risk factor for OS.CHCC patients appear to have intermediate clinical characteristics in comparison with the HCC and ICC patients, and the 1-year DFS and OS for the CHCC patients was worse than the HCC patients, but similar to the ICC patients.

Major hepatectomy for intrahepatic cholangiocarcinoma or colorectal liver metastases. Are we talking about the same story?

IntroductionMajor hepatectomy (MH) is often needed in the curative management of intrahepatic cholangiocarcinoma (IHCC) and colorectal liver metastases (CRLM). While similar outcomes could be expected after MH for IHCC and CRLM, outcomes seem worse after MH for IHCC. A better understanding of such differences might help improving perioperative outcomes but comprehensive analysis are lacking. MethodsAll patients undergoing curative intent MH for IHCC or CRLM from 2003 to 2009 were included from two dedicated multi-institutional datasets. Preoperative management and short-term outcomes after MH were first compared. Independent predictors of postoperative mortality and morbidity were identified. ResultsAmong 827 patients, 333 and 494 patients underwent MH for IHCC and CRLM, respectively. Preoperative portal vein embolization was more frequently performed in the CRLM group (p < 0.001). MH in the IHCC group required more extended resection (p < 0.001). Postoperative mortality and severe morbidity rates were significantly higher in the IHCC group (7.2% vs. 1.2% and 29.7% vs. 11.1%, p < 0.001, respectively). Main causes for mortality were postoperative liver failure and deep surgical site infection. MH for IHCC was an independent risk factor for mortality (p < 0.001) and severe morbidity (p < 0.001). After propensity score matching (212 patients in each group), the aforementioned differences regarding outcomes remained statistically significant. ConclusionThis study suggests that IHCC patients are inherently more at risk after MH as compared to CRLM patients. Considering that postoperative liver failure was the most frequent cause of death, preoperative planning might have been inadequate in the setting of IHCC while more complex/extended resections should be expected.