Mass-forming Intrahepatic Cholangiocarcinoma Research Articles

Clinical Outcomes of Mass-Forming Intrahepatic Cholangiocarcinoma: A Case Series of 68 Patients

Clinical Outcomes of Mass-Forming Intrahepatic Cholangiocarcinoma: A Case Series of 68 Patients

Association of inflammatory biomarkers with long-term outcomes after curative surgery for mass-forming intrahepatic cholangiocarcinoma.

Inflammatory biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are reportedly predictive of the long-term outcomes of several cancers. We evaluated their correlations with the post-surgical long-term outcomes of patients with mass-forming (MF) intrahepatic cholangiocarcinoma (ICC). The subjects of this study were 52 patients who underwent hepatic resection for MF-ICC at our hospital. We measured the cutoff values of NLR, LMR and PLR, using receiver operating characteristic curves, and compared the survival rates of patients with high vs. those with low values. We also evaluated a prognostic scoring system based on significant inflammatory biomarkers. The cutoff values for NLR, LMR, and PLR were 1.93, 4.78, and 98, respectively. The high-NLR and low-LMR groups had significantly worse prognoses than the low-NLR and high-LMR groups. We designed a scoring system using the inflammation score (IS) based on NLR and LMR values, stratifying patients into three groups with scores of 0, 1, or 2. The IS was significantly correlated with overall survival (OS), with 5-year survival rates by the IS score of 100% for 0, 61% for 1, and 32% for 2 (P = 0.011). The IS was found to be an independent predictor of OS in multivariate analysis. Our IS scoring system may predict long-term outcomes after surgery for MF-ICC.

Role of Intravoxel Incoherent Motion in Discriminating Hepatitis B Virus-Related Intrahepatic Mass-Forming Cholangiocarcinoma from Hepatocellular Carcinoma Based on Liver Imaging Reporting and Data System v2018.

Backgroud: Intravoxel incoherent motion (IVIM) could be used to characterize benign and malignant hepatic lesions and predict the histological grade of hepatocellular carcinoma (HCC). To evaluate IVIM-derived parameters for differentiating between hepatitis B virus (HBV)-related intrahepatic mass-forming cholangiocarcinoma (IMCC) and HCC based on the Liver Imaging Reporting and Data System (LI-RADS) v2018. Materials and Methods: 20 IMCC patients and one-to-one matched control HCC patients were retrospectively assessed. IVIM scanning with 11 b-values (from 0 to 1500 s/mm2) was obtained using a 3.0-T magnetic resonance scanner. Apparent diffusion coefficient (ADC) and IVIM parameters, including diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f), were compared between IMCC and HCC. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performances of ADC, D, f, and D*. The LI-RADS features and a final category were also compared using LI-RADS v2018. Results: ADC and D were significantly higher in IMCC than in HCC (p = 0.012 and p = 0.007, respectively); f was significantly higher in HCC than in IMCC (p = 0.004). The area under the ROC curve values for ADC, D, and f for differentiating HBV-related IMCC from HCC were 0.724, 0.753, and 0.741, respectively. Conclusion: The majority of HBV-related IMCCs can be categorized as LR-M by using LI-RADS. However, atypical IMCCs may be classified as non-LR-M. ADC, D, and f values may be helpful in differentiating HBV-related IMCC from HCC, and similar diagnostic performances were obtained for these values.

Prediction for early recurrence of intrahepatic mass-forming cholangiocarcinoma: quantitative magnetic resonance imaging combined with prognostic immunohistochemical markers

BackgroundPartial hepatectomy is the first option for intrahepatic mass-forming cholangiocarcinoma (IMCC) treatment, which would prolong survival. The main reason for the poor outcome after curative resection is the high incidence of early recurrence (ER). The aim of this study was to investigate the combined predictive performance of qualitative and quantitative magnetic resonance imaging (MRI) features and prognostic immunohistochemical markers for the ER of IMCC.MethodsForty-seven patients with pathologically proven IMCC were enrolled in this retrospective study. Preoperative contrast-enhanced MRI and post-operative immunohistochemical staining of epidermal growth factor receptors (EGFR), vascular endothelial growth factor receptor (VEGFR), P53 and Ki67 were performed. Univariate analysis identified clinic-radiologic and pathological risk factors of ER. Radiomics analysis was performed based on four MRI sequences including fat suppression T2-weighted imaging (T2WI/FS), arterial phase (AP), portal venous phase (PVP), and delayed phase (DP) contrast enhanced imaging. A clinicoradiologic-pathological (CRP) model, radiomics model, and combined model were developed. And ROC curves were used to explore their predictive performance for ER stratification.ResultsEnhancement patterns and VEGFR showed significant differences between the ER group and non-ER group (P = 0.001 and 0.034, respectively). The radiomics model based on AP, PVP and DP images presented superior AUC (0.889, 95% confidence interval (CI): 0.783–0.996) among seven radiomics models with a sensitivity of 0.938 and specificity of 0.839. The combined model, containing enhancement patterns, VEGFR and radiomics features, showed a preferable ER predictive performance compared to the radiomics model or CRP model alone, with AUC, sensitivity and specificity of 0.949, 0.875 and 0.774, respectively.ConclusionsThe combined model was the superior predictive model of ER. Combining qualitative and quantitative MRI features and VEGFR enables ER prediction, thus facilitating personalized treatment for patients with IMCC.

Should Utilization of Lymphadenectomy Vary According to Morphologic Subtype of Intrahepatic Cholangiocarcinoma?

We sought to evaluate the utilization of lymphadenectomy (LND) and the incidence of lymph node metastasis (LNM) among different morphologic types of intrahepatic cholangiocarcinoma (ICC). Clinical data of patients undergoing curative-intent resection for ICC between 1990 and 2017 were collected and analyzed. The preoperative nodal status was evaluated by imaging studies, and the morphologic and lymph node (LN) status was collected on final pathology report. Overall, 1032 patients had a mass-forming (MF) or intraductal growth (IG) ICC subtype, whereas 150 patients had a periductal infiltrating (PI) or MF + PI subtype. Among the 924 patients with MF/IG ICC subtype who had nodal assessment on preoperative imaging, 747 (80.8%) were node-negative, whereas 177 (19.2%) patients were suspicious for metastatic nodal disease. On final pathological analysis, 71 of 282 (25.2%) patients who had preoperative node-negative disease ultimately had LNM. In contrast, 79 of 135 (58.5%) patients with preoperative suspicious/metastatic LNs had pathologically confirmed LNM (odds ratio [OR] 4.2, p < 0.001). Among the 129 patients with PI/MF + PI ICC subtype and preoperative nodal information, 72 (55.8%) were node-negative on preoperative imaging. In contrast, 57 (44.2%) patients had suspicious/metastatic LNs. On final pathologic examination, 45.3% (n = 24) of patients believed to be node-negative on preoperative imaging had LNM; 68.0% (n = 34) of patients who had suspicious/positive nodal disease on imaging ultimately had LNM (OR 2.6, p = 0.009). Given the low accuracy of preoperative imaging evaluation of nodal status, routine LND should be performed at the time of resection for both MF/IG and PI/MF + PI ICC subtypes.

Indications for laparoscopic liver resection of mass-forming intrahepatic cholangiocarcinoma.

We investigated the indications for laparoscopic liver resection (LLR) of mass-forming intrahepatic cholangiocarcinoma (MF-ICC), including the need for lymph node dissection for improved postoperative prognosis. This study involved 36 patients who underwent surgery for solitary peripheral MF-ICC. Fifteen patients underwent LLR, and 21 underwent open liver resection (OLR). Surgical outcomes and prognostic factors were investigated to determine the indications for LLR. No significant differences were observed in perioperative outcomes between patients who underwent LLR and OLR. A significantly worse disease-free survival (DFS) rate was observed in patients who preoperatively had a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) levels. A significantly worse overall survival (OS) rate was observed in patients with a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 levels. Therefore, a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 and CEA levels were determined to be preoperative prognostic factors. DFS and OS rates were significantly better in patients without these factors. Moreover, in six patients without these factors who underwent LLR, neither lymph node metastasis nor postoperative recurrence was observed. A tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 and CEA levels are preoperative prognostic factors for peripheral MF-ICC. LLR is indicated for patients without these factors.

Role of central hypovascularity in the hepatic arterial phase of dynamic CT on mass-forming intrahepatic cholangiocarcinoma.

205 Background: Intrahepatic cholangiocarcinoma (IHCC) is known as one of most malignant cancers. Recently, the vascularity in the hepatic arterial phase (HAP) of dynamic CT has been reported as a possible prognostic marker in IHCC. The aim of this study is to elucidate the role of central hypovascularity in the HAP on mass-forming IHCC. Methods: Forty patients who underwent initially hepatic resection for mass-forming IHCC were enrolled. The HAP was scanned 40 seconds after the injection of contrast agent. Vascular pattern was classified into three groups; hypervascularity (Hyper) group (n = 8), rim-enhancement (Rim) group (n = 7) and hypovascularity (Hypo) group (n = 25) by a radiologist in reference to Fujita, et al (Eur Radiol 2017). Hypoxia-inducible factor-1 (HIF-1) expression in the surgical specimen was evaluated by immunohistochemistry. The clinicopathological findings were compared among the groups. Results: The advanced stage tended to be more frequent in Hypo group, however, no difference of tumor location (hilar or peripheral) was observed. Overall survival (OS) in Hypo group was worse than that in Hyper group. The OS in Rim+Hypo group, that means central hypovascularity in the tumor, was worse than that in Hyper group. Furthermore, Rim+Hypo group was an independent prognostic factor in OS (HR: 5.44). Regarding the HIF-1 expression, high HIF-1 expression in the central part of the tumor correlated with central hypovascularity in the HAP (25% in Hyper-group and 72% in Rim+Hypo group, respectively). Conclusions: The central hypovascularity (Rim+Hypo group) was an independent prognostic factor, furthermore, high malignant potential of the tumor with central hypovascularity might be related to HIF-1 upregulation.

Absolute Neutrophil Count Predicts Postoperative Prognosis in Mass-forming Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (IHCC) is characterized by poor prognosis, and postoperative recurrence remains a problem. Thus, prognostic markers for IHCC are greatly needed. Recently, inflammatory factors were reported to be related to tumor progression and recurrence in various cancers. Therefore, the present study aimed to evaluate the prognostic ability of inflammatory factors. Forty-four patients with mass-forming IHCC (m-IHCC) were retrospectively evaluated and the correlations between inflammatory markers, including neutrophil-to-lymphocyte ratio and, modified Glasgow prognostic score, and patient survival were assessed. The absolute neutrophil count (ANC) was significantly higher in the recurrence group than in the non-recurrence group (p=0.00568) and the most significant prognostic factor by multivariate analysis. Poor recurrence-free survival (RFS; p=0.00452) and cancer-specific survival (CSS; p=0.0323) were associated with high neutrophil levels. Moreover, neutrophil infiltration in the tumor site was positively correlated with ANC. ANC is associated with poor RFS, and could be used to predict recurrence in patients with m-IHCC.

Intrahepatic Mass-forming Cholangiocarcinoma: Arterial Enhancement Patterns at MRI and Prognosis.

Purpose To identify whether arterial enhancement pattern at MRI could predict the prognosis after surgical resection of intrahepatic mass-forming cholangiocarcinoma (IMCC). Materials and Methods Patients who underwent curative hepatic resection and preoperative MRI for IMCC from November 2007 to September 2016 were retrospectively evaluated. MRI enhancement pattern was classified by two radiologists. Recurrence and death data were retrieved until September 31, 2017. Prognostic factor analysis was performed by using preoperative and postoperative clinical-pathologic factors, as well as imaging findings. Results Data in 134 patients (median age, 63.0 years; 87 men and 47 women) were evaluated; median tumor size was 4.5 cm. Arterial phase MRI showed diffuse hypoenhancement in 33 patients, peripheral rim enhancement in 81 patients, and diffuse hyperenhancement in 20 patients. The 5-year risk of death in patients with IMCC with diffuse hyperenhancement was lower than that of patients with diffuse hypoenhancement or peripheral rim enhancement (5-year risk of death: 5.9% vs 87.9% vs 59.2%). Diffuse hypoenhancement (hazard ratio [HR], 41; 95% confidence interval [CI]: 5, 312; P < .01) and peripheral rim enhancement (HR, 11; 95% CI: 2, 85; P = .02) were associated with an increased risk of death compared with diffuse hyperenhancement. Patients with diffuse hyperenhancement of IMCCs had more frequent chronic liver disease (13 of 20; 65%), less frequent vascular invasion (six of 20; 30%), and less frequent tumor necrosis (three of 20; 15%) than other enhancement group (P < .05 for all). Conclusion The MRI arterial enhancement pattern was a prognostic marker in the preoperative evaluation of patients with resectable intrahepatic mass-forming cholangiocarcinoma. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Yoon and Lee .

A proposal of imaging classification of intrahepatic mass-forming cholangiocarcinoma into ductal and parenchymal types: clinicopathologic significance.

To investigate the clinicopathologic significance of a subclassification of mass-forming intrahepatic cholangiocarcinoma (MF-iCCA) into ductal and parenchymal types based on magnetic resonance imaging (MRI) METHODS: We enrolled 72 consecutive patients, in whom MF-iCCA was diagnosed on preoperative MRI and surgical resection from January 2000 to March 2013. Two readers independently evaluated MRI findings of adjacent bile duct dilation, periductal tumor spread, and presence of diffuse dilatation or abnormality of the intrahepatic bile duct. MF-iCCAs with none of the aforementioned findings were defined as parenchymal type, and those with one or more findings were defined as ductal type. The enhancement pattern in the arterial phase was also evaluated. Clinical and histopathological findings, as well as post-surgical outcomes, were collected from medical records. Parenchymal-type MF-iCCA (21/78, 27%) exhibited significantly lower serum carbohydrate antigen 19-9 (12.8 vs. 173.8U/mL) and carcinoembryonic antigen (1.7 vs. 4.2ng/mL), more frequent viral hepatitis (43% vs. 18%), less frequent biliary intraepithelial neoplasia (0% vs. 26%), and less frequent perineural invasion (0% vs. 59%) and lymph node metastasis (7% vs. 46%), compared with the ductal type (57/78, 73%) (p < 0.05 for all). Parenchymal-type MF-iCCA showed more frequent arterial hypervascularity (p = 0.001) and better overall survival (p = 0.030) than the ductal type. Subclassification of MF-iCCAs into parenchymal and ductal types may be useful to discriminate clinical and histopathological characteristics and post-surgical outcomes. • We propose subclassification of mass-forming intrahepatic cholangiocarcinoma (MF-iCCA) as parenchymal and ductal types, on the basis of magnetic resonance imaging findings of biliary abnormality. • Two types of MF-iCCAs exhibit different clinical and histopathological characteristics and post-surgical outcomes.

Mass-forming intrahepatic cholangiocarcinoma: Can diffusion-weighted imaging predict microvascular invasion?

Microvascular invasion (MVI) is a risk factor influencing the survival rate of patients with mass-forming intrahepatic cholangiocarcinoma (IMCC). To investigate whether diffusion-weighted imaging (DWI) could be useful in predicting MVI of IMCC. Retrospective. Eighty patients with surgically resected single IMCC (21 MVI-positive lesions and 59 MVI-negative lesions). Preoperative hepatic MRI (1.5T), including T1 - and T2 -weighted images (T1 WI, T2 WI), DWI, and dynamic enhancement imaging. Morphologic characteristics including contour of the lesion, biliary dilation and hepatic capsule retraction, signal features on T1 WI, T2 WI, and DWI, and dynamic enhancement patterns were qualitatively evaluated. The quantitative analysis was performed for the size and apparent diffusion coefficient (ADC) values. Chi-square test, Fisher's exact test, and the independent t-test were used for univariate analysis to determine the relationships between these radiological parameters and the presence of MVI. Logistic regression analysis was used to identify the independent predictors of MVI among these radiological parameters. Receiver operating characteristic curve analysis was performed to evaluate their diagnostic performance. Larger tumor size (P = 0.006) and higher ADC values (P < 0.001) were positively correlated with MVI. Multivariate logistic regression analysis demonstrated that the ADC value (odds ratio, 3.099; P = 0.001) was an independent predictor for MVI of IMCC. The ADC value for MVI of IMCC showed an area under the receiver operating characteristic curve of 0.782 (optimal cutoff value was 1.59 × 10-3 mm2 /s). Larger tumor size was associated with MVI and higher ADC values can be a useful predictor of MVI during the preoperative evaluation of IMCC. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:315-324.

A case of intrahepatic cholangiocarcinoma that was difficult to diagnose prior to surgery: A case report.

The present study reports a case of mass-forming intrahepatic cholangiocarcinoma (ICC), which mimicked cholangiocellular carcinoma (CoCC) during imaging and a needle biopsy examination. A 51-year-old female with no relevant medical history was referred to the National Defense Medical College hospital with an intrahepatic tumor. Computed tomography demonstrated non-homogeneous enhancement in the early arterial phase and persistent enhancement in the portal and equilibrium phases, together with notable swelling of the para-aortic lymph nodes. Gadolinium-ethoxybenzyl diethylenetriamine-pentaacetic acid-enhanced magnetic resonance imaging revealed low signal intensity in the hepatobiliary phase. The liver tumor and lymph nodes exhibited increased radiotracer uptake (maximum standardized uptake value=14.0) with positron emission tomography. A histological examination of a percutaneous needle biopsy specimen of the liver tumor indicated a diagnosis of CoCC. The patient underwent left hepatectomy and lymphadenectomy. The surgical specimen contained a poorly differentiated adenocarcinoma with anaplastic changes, which was immunohistochemically positive for epithelial membrane antigen (at the luminal membrane), cytokeratins 7 and 19, and negative for α-fetoprotein, hepatocyte-specific antigen, cluster of differentiation 56 and KIT. Based on these histopathological and immunohistochemical findings, the patient was diagnosed with ICC.

Enhancement Patterns of Intrahepatic Cholangiocarcinoma on Contrast-Enhanced Ultrasound: Correlation with Clinicopathologic Findings and Prognosis

To evaluate the correlations between the enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and clinicopathologic findings and prognosis, a retrospective study was performed on 197 patients with mass-forming ICC who underwent pre-operative CEUS and surgical resection. The contrast medium we employed in CEUS was SonoVue, which contains microbubbles consisting of sulfur hexafluoride bubbles within a phospholipid shell. This study was approved by the institutional review board with informed consent waived. Patients were classified into an arterial rim-like enhancement group or an arterial non-rim-like enhancement group, and arterial enhancement patterns were correlated with clinicopathologic factors. Overall survival (OS) times were calculated using the Kaplan–Meier method, and differences between groups were compared with the log-rank test. Univariate and multivariate Cox regression models for OS were used to evaluate the independent prognostic factors. The mean and range of ICC tumor size of the arterial rim-like group (59.41 ± 22.09 mm, 20–100 mm) were similar to those of the arterial non-rim-like group (59.82 ± 30.35 mm, 14–162 mm, p = 0.914). Arterial enhancement patterns were correlated with chronic viral hepatitis or cirrhosis, vascular invasion, lymph node metastasis and single/multiple tumors. A total of 78 patients (39.6%) exhibited arterial rim-like enhancement, and the other 119 patients (60.4%) exhibited arterial non-rim-like enhancement. Arterial enhancement pattern (p = 0.045), vascular invasion (p = 0.005), lymph node metastasis (p = 0.000) and number of tumors (p = 0.001) were independent prognostic factors for OS. The arterial non-rim-like enhancement pattern of ICC on CEUS is an independent prognostic factor for better OS and may offer new information for predicting the prognosis of ICC patients before surgical resection.

Volumetric Apparent Diffusion Coefficient Histogram Analysis in Differentiating Intrahepatic Mass-Forming Cholangiocarcinoma From Hepatocellular Carcinoma.

Accurate differentiation between intrahepatic mass-forming cholangiocarcinoma (IMCC) and hepatocellular carcinoma (HCC) is needed because treatment and prognosis differ significantly. To explore whether volumetric apparent diffusion coefficient (ADC) histogram analysis can provide additional value to dynamic enhanced MRI in differentiating IMCC from HCC. Retrospective. In all, 131 patients with pathologically proven IMCC (n = 33) or HCC (n = 98). 3.0T MRI/conventional T1 -weighted imaging (T1 WI), T2 WI, and diffusion-weighted imaging (DWI) with b value of 800 sec/mm2 , dynamic enhanced MRI with gadobenate dimeglumine. Dynamic enhanced MR images were analyzed by two independent reviewers using a five-point scale to determine the diagnosis. Volumetric ADC assessments were performed independently by two radiologists to obtain different histogram parameters for each lesion. Quantitative histogram parameters were compared between the IMCC group and HCC group. Diagnostic performance of dynamic enhanced MRI, volumetric ADC histogram analysis, and the combination of both were analyzed. Intraclass correlation coefficient (ICC) analysis, independent Student's t-test, or Mann-Whitney U-test, receiver operator characteristic (ROC) curves analysis, and McNemar test. The sensitivity and specificity for dynamic enhanced MRI to differentiate IMCC from HCC were 82.1% and 82.6%, respectively. For all volumetric ADC histogram parameters, the 75th percentile ADC (ADC75% ) had the highest AUC (0.791) in differentiating IMCC from HCC, with sensitivity and specificity of 69.7% and 77.6%, respectively. When combining dynamic enhanced MRI with ADC75% , the sensitivity and specificity were 82.1% and 91.9%, respectively. Compared to dynamic enhanced MRI alone, the specificity for combined dynamic enhanced MRI and ADC75% was significantly increased (P = 0.008). Volumetric ADC histogram analysis provides additional value to dynamic enhanced MRI in differentiating IMCC from HCC. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:975-983.

Lymphoid infiltrate predicts prognosis of mass-forming intrahepatic cholangiocarcinoma undergoing complete liver resection

Introduction: The lymphoid infiltrate has shown a prognostic impact in several tumors. No study focused on intrahepatic mass-forming cholangiocarcinoma (MFCCC). Methods: All consecutive patients undergoing surgery for MFCCC between 2005 and 2015 were considered. The inclusion criteria were complete resection and follow-up ≥12 months. Patients with operative mortality were excluded. Tissue sections from MFCCC were immunostained for CD3+, CD4+, CD8+, Foxp3+ and CD68+. Results: Overall, 53 patients were analyzed. MFCCC were multiple in 10 patients, >50 mm in 26, and N+ in 12. At univariate analysis, the following lymphoid infiltrate values had a prognostic impact: CD3+ >0.10% (overall survival, OS p< 0.001, recurrence-free survival, RFS p< 0.001); CD8+ >0.10% (OS p=0.044, RFS p=0.001), CD4+ >0.30% (OS p=0.094, RFS p=0.009), and Foxp3+ present (OS p=0.097). At multivariable analysis, CD3+ value was a prognostic factor of OS and RFS [>0.10%, 5-year OS 66.9% vs. 18.2% if ≤0.10%, HR=0.287, p=0.049; 3-year RFS 48.1% vs. 9.1%, HR=0.232, p=0.001] and Foxp3+ was a prognostic factor of OS [present, 5-year OS 21.4% vs. 61.9% if absent, HR=2.924, p=0.044].CD3+ values stratified prognosis in T1 patients (5-year OS 73.9%/14.3%, p< 0.001; 3-year RFS 60.8%/14.3%, p< 0.001), in N+ patients (OS 71.4%/0%, p=0.028; RFS 42.9%/0%, p=0.011) and in patients without lymph-node metastases (RFS 49.7%/20.0%, p=0.062). Conclusions: The lymphoid infiltrate impacts prognosis of MFCCC after complete surgery. CD3+ infiltrate is associated with higher survival and lower recurrence risk, while Foxp3+ is associated with worse prognosis. CD3+ infiltrate allows to refine prognosis in early tumors and across different N stages.

A Radiomics Approach Predicts Lymph Node Metastasis and Clinical Outcomes in Intrahepatic Mass-Forming Cholangiocarcinoma

Background: To develop and validate a radiomics model for predicting lymph node (LN) metastasis in intrahepatic mass-forming cholangiocarcinoma (IMCC), and to determine its prognostic value. Methods: A radiomics model was developed in a primary cohort of 103 IMCC patients who underwent curative-intent resection and regional lymphadenectomy. Radiomic features were extracted from arterial-phase computed tomography (CT) scans. A radiomics signature was built based on high reproducible features using the Lasso method. Multivariate logistic regression analysis was adopted to establish a radiomics model incorporating radiomics signature and other independent predictors. Model performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 52 consecutive patients. Findings: The radiomics signature comprised eight LN-status-related features and showed significant association with LN metastasis in both cohorts (P<0.001). A radiomics nomogram that incorporates radiomics signature and CA 19-9 level showed good calibration and discrimination in primary cohort (AUC 0.8462) and validation cohort (AUC 0.8921). Promisingly, the radiomics nomogram yielded an AUC of 0.9224 in CT-reported LN-negative subgroup. Decision curve analysis confirmed the clinical utility of this nomogram. High-risk metastasis portended significantly lower overall and recurrence-free survival than low-risk metastasis (both P<0.001). The radiomics nomogram represented an independent preoperative predictor of overall and recurrence-free survival. Interpretation: Our radiomics nomogram provides an individualized approach for preoperative detection of LN metastasis in IMCC patients, especially in CT-reported LN-negative patients. This model allows prediction of the metastasizing potential of IMCCs with poor prognosis even after curative-intent resection and thus may improve clinical decision-making. Funding: This study was supported by the Natural Science Foundation of China (81530048, 81470901, 81670570), and the Key research and development program of Jiangsu Province (BE2016789). Declaration of Interest: All authors declare no potential conflicts of interest. Ethical Approval: The ethics committee of Nanjing Medical University approved this retrospective analysis and waived the requirement for informed consent.

Gadoxetic acid enhanced magnetic resonance imaging for prediction of the postoperative prognosis of intrahepatic mass-forming cholangiocarcinoma.

To identify imaging markers that independently predict the post-operative outcome of intrahepatic mass-forming cholangiocarcinoma (IMCC) using gadoxetate disodium-enhanced magnetic resonance imaging (MRI). Data from 54patients who underwent pre-operative gadoxetate disodium-enhanced MRI and curative surgery for IMCC were retrospectively evaluated. The prognostic power of various imaging and pathological features reportedly associated with recurrence-free survival (RFS) and overall survival (OS) was analyzed using Cox regression models. A model combining imaging and pathological features was developed and its performance was evaluated using the Harrell C-index and Akaike information criterion. Capsule penetration (P = 0.016) and tumor size (P = 0.015) were independent markers for worse RFS, while capsule penetration (P = 0.012) and hepatic vein obstruction (HVO, P = 0.016) were independent markers for worse OS, respectively, in the imaging-based model. Capsule penetration was the only imaging marker identified in the combined prediction model of RFS, and the combined model showed a higher C-index and lower AIC value compared with the model based on pathological features alone. Capsule penetration and HVO on MRI are significantly worse imaging prognostic factors for post-operative outcomes in patients with IMCC. Incorporation of capsule penetration and HVO into a surgical staging system may improve prediction of the post-operative prognosis of IMCC.

Long-term outcomes of patients with intraductal growth sub-type of intrahepatic cholangiocarcinoma

BackgroundIntraductal-growth (IG) type of intrahepatic cholangiocarcinoma (ICC) may be associated with a favorable prognosis compared with mass-forming (MF) and periductal-infiltrating (PI) ICC. MethodsThe clinico-pathological characteristics and long-term outcomes of 1206 patients undergoing liver resection for ICC were compared based on the ICC morphological classification. ResultsCompared with MF patients, IG patients had a higher incidence of poor/un-differentiated tumor, lympho-vascular, and perineural invasion (poor/un-differentiated: MF, 18% vs. IG, 24%; lympho-vascular invasion: MF, 30% vs. IG, 35%; perineural invasion: MF, 17% vs. IG, 33%; all p > 0.05). The pattern of recurrence was different among MF patients (intrahepatic only: 63%; extrahepatic only: 22%; both intra- and extrahepatic: 16%) versus IG patients (intrahepatic only: 46%; extrahepatic: 25%; both intra- and extrahepatic: 29%) (p < 0.001). Moreover, while 78% of patients with MF had an early recurrence (<18 months from surgery), 59% of IG patients had and early recurrence (p = 0.039). On multivariable analysis, after controlling for competing risk factors, IG patients had a similar prognosis as MF patients (HR 0.90, p = 0.69). ConclusionWhile IG patients more frequently presented with more adverse pathological characteristics, the prognosis of IG patients was comparable with MF patients after controlling for all these adverse factors.

Resected primary mucinous cholangiocarcinoma of the liver

BackgroundMucinous cholangiocarcinoma (MC) is a very rare variant of intrahepatic cholangiocarcinoma. MC is characterized by rapid growth, widespread metastasis, and poor prognosis. We report a case of resected MC of the liver.Case presentationWe found a 13.6-cm hypovascular tumor in the left hepatic lobe of a 68-year-old man, which we initially diagnosed as a mass-forming intrahepatic cholangiocarcinoma. Left lobe and caudate resection was performed without major intraoperative or postoperative complications. He was discharged home on postoperative day 9 and had no recurrence for 6 months. Pathological examination showed a mucous lobulated tumor with abundant mucus in the cytoplasm and extracellular regions. After differential diagnosis that considered invasive intraductal papillary neoplasm of the bile duct and metastatic liver tumors from the digestive tract, this tumor was diagnosed as a cholangiocarcinoma rare variant: primary mucinous carcinoma of the liver.ConclusionAnalysis of previous reports suggests that primary MC of the liver could be classified into two subtypes: pure MC and combined hepatocellular carcinoma and MC. Notably, the latter has been reported only in patients with chronic liver disease, whereas the former has only been reported in patients with no underlying disease.

Intrahepatic Mass-Forming Cholangiocarcinoma: Relationship Between Computed Tomography Characteristics and Histological Subtypes.

The aim of this study was to determine the value of multi-detector row computed tomography (MDCT) in differentiating the small-duct (SD) and large-duct (LD) types of intrahepatic mass-forming cholangiocarcinomas (IMCCs) and predicting patient prognosis. The 4-phase MDCT image findings of 82 patients with surgically confirmed IMCCs (60 SD-type and 22 LD-type IMCCs) were compared between 2 types using univariate and multivariate analyses. Overall survival rates for 78 patients with available information were compared using the Kaplan-Meier method. Arterial hyperenhancement, round or lobulated contour, and lack of bile duct encasement were significant MDCT features suggesting the SD type, and lymph node enlargement was significantly associated with the LD type (all P's < 0.05). The presence of those 3 SD-type-suggestive features (MDCT-suggested SD type) demonstrated high specificity (90.9% [20/22]) in differentiating the SD type. Patients of MDCT-suggested SD type without lymph node enlargement (n = 24) demonstrated significantly better overall survival than other groups. Preoperative MDCT features of IMCCs can help differentiate the SD and LD types and predict patient prognosis.