Purpose:To explore the application value of clinical indicators, radiological features, and magnetic resonance imaging (MRI) radiomics to predict the grading of MVI in nodular hepatocellular carcinoma (≤3cm). Methods:A total of 131 patients with hepatocellular carcinoma (HCC) and confirmed microvascular invasion (MVI) who underwent surgical resection between January 2016 and December 2022 were retrospectively analyzed. A clinical-radiological (CR) model was constructed using independent risk factors identified by logistic regression. Radiomics models based on MRI (arterial phase, portal venous phase, delayed phase) across various regions (AVDPintra, AVDPintra+peri3mm, AVDPintra+peri5mm, AVDPintra+peri10mm) were developed using the Logistic Regression (LR) classifiers. The optimal radiomics model was subsequently integrated with the CR model to construct a combined clinical-radiological-radiomics (CRR) model. Model performance was assessed using the area under the curve (AUC). Results:Non-smooth margin and intratumoral artery were risk factors for MVI grading. The combined CRR model demonstrated the best predictive performance, with AUCs of 0.907 and 0.917 in the training and testing sets, respectively. Compared with the CR model alone, the CRR model showed a statistically significant improvement (p = 0.008, DeLong test). Conclusion:The AVDPintra+peri3mm model based on MRI radiomics demonstrates good predictive performance in predicting MVI grading in HCC (≤3cm). Combining features from the CR model with those of the AVDPintra+peri3mm model to construct the CRR model further enhances the prediction of MVI grading.

Tumors often exhibit oxygen deprivation and enhanced glucose uptake, leading to glycolysis. Advanced glycation end products (AGEs) protein modifications induced by hyperglycemia—activate signaling pathways that promote cancer progression upon binding to its receptor (RAGE). In this study, AGEs-treatment enhanced the growth, invasion and migration of intrahepatic cholangiocarcinoma cells (ICC), while increasing IL-6 expression and secretion. Meanwhile, AGEs stimulated the expression of RAGE, specificity protein 1 (Sp1), and the phosphorylation of extracellular signal-regulated kinase (ERK) in a dose-dependent manner. However, these effects were attenuated by RAGE antibody blockade, RAGE knockdown, the ERK inhibitor U0126, or Sp1-specific siRNA. Furthermore, the supernatant of AGEs-treated RBE cells induced M2 polarization of THP-1 macrophages. Thus, AGEs promote ICC progression partly through the pERK/Sp1/IL-6 pathway and M2 macrophage polarization. These findings highlight underscore the role of the AGEs-RAGE axis in driving ICC progression via pERK/Sp1/IL-6 signaling.

Objective:This study aims to evaluate the prognostic predictive efficacy of Gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging (MRI) in patients with solitary hepatocellular carcinoma (HCC) without microvascular invasion (MVI) and to investigate the potential clinical and imaging parameters for stratifying the risk of recurrence following hepatectomy. Methods:This retrospective study included 134 patients with histopathologically confirmed solitary HCC without microvascular invasion (MVI) from two hospital districts, which divided into the training cohort and validation cohort. MRI features were independently assessed by two radiologists. Univariate and multivariate Cox regression analyses were conducted to identify independent risk factors associated with recurrence-free survival (RFS). A nomogram was developed based on these factors, and its performance was validated in the validation cohort. RFS was analyzed using Kaplan-Meier curves and the Log rank test. Results:The median RFS for the 134 patients was 45.7 months, with 41.8% of patients experiencing tumor recurrence after hepatectomy. Univariate Cox regression analysis identified hepatitis Be antigen (HBeAg) positivity, tumor size, tumor growth subtype, non-peripheral washout, nodule-in-nodule architecture, mosaic architecture, and intratumoral arteries as significant risk factors for RFS. Multivariate Cox regression analysis revealed that HBeAg positive, tumor growth subtype, non-peripheral washout, mosaic architecture, and internal arteries were independent prognostic factors for RFS in patients with solitary HCC without MVI. The nomogram based on these variables demonstrated good predictive accuracy, with concordance indices (C-index) of 0.740 and 0.701 in the training and validation cohorts, respectively. Additionally, patients in the high-risk group exhibited significantly lower RFS compared to those in the low-risk group. Conclusion:A model incorporating Gd-BOPTA-enhanced MRI and clinical features can effectively predict RFS in solitary HCC patients without MVI and assist in risk stratification for recurrence after hepatectomy.

Objective:This study aims to investigate the predictive value of Gadobenate dimeglumine (Gd-BOPTA) enhanced MRI features on microvascular invasion (MVI) and recurrence in patients with Liver Imaging Reporting and Data System (LI-RADS) category 5 hepatocellular carcinoma (HCC).Methods:A total of 132 patients with LI-RADS category 5 HCC who underwent curative resection and Gd-BOPTA enhanced MRI at our hospital between January 2016 and December 2018 were retrospectively analyzed. Qualitative evaluation based on LI-RADS v2018 imaging features was performed. Logistic regression analyses were conducted to assess the predictive significance of these features for MVI, and the Cox proportional hazards model was used to identify postoperative risk factors of recurrence. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier curve and Log rank test.Results:Multivariate logistic regression analysis identified that corona enhancement (odds ratio [OR] = 3.217; p < 0.001), internal arteries (OR = 4.147; p = 0.004), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR = 5.165; p < 0.001) were significantly associated with MVI. Among the 132 patients with LR-5 HCC, 62 patients experienced postoperative recurrence. Multivariate Cox regression analysis showed that mosaic architecture (hazard ratio [HR] = 1.982; p = 0.014), corona enhancement (HR = 1.783; p = 0.039), and peritumoral hypointensity on HBP (HR = 2.130; p = 0.009) were risk factors for poor RFS.Conclusion:MRI features based on Gd-BOPTA can be noninvasively and effectively predict MVI and recurrence of LR-5 HCC patients.

Objective: Microvascular invasion (MVI) is significantly associated with prognosis in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) patients. The study aimed to explore the value of preoperative contrast -enhanced CT (CECT) features and clinical data in predicting MVI of cHCC-CCA.Methods: A total of 33 patients with MVI-positive and 27 with MVI-negative were enrolled, and underwent preoperative CECT imaging from January 2016 to December 2021. Preoperative clinical data and CECT imaging features were retrospectively analyzed. Univariable and multivariable logistic regression analysis were per-formed to identify potential predictors of MVI in cHCC-CCA. The diagnostic performance was evaluated by the receiver operating characteristic (ROC) curve and its area under the curve (AUC) value.Results: The mean age of the patients was 54.0 +/- 10.3 years, and 53 of the 60 patients (88.3%) were male. Preoperative imaging features on CECT (non-smooth contour and arterial phase peritumoral enhancement) and clinical data (hepatitis B virus (HBV) infection and protein induced by vitamin K absence or antagonist-II (PIVKA-II)) were highly distinct between those in MVI-positive group and MVI-negative group. On multivariable logistic analysis, arterial phase peritumoral enhancement (odds ratio (OR), 6.514; 95% confidence interval (CI), 1.588-26.728, p = 0.012) and high serum PIVKA-II level (OR, 6.810; 95% CI, 1.796-25.820, p = 0.005) were independent predictors associated with MVI of cHCC-CCA. The combination of these two predictors had high sensitivity (31/33, 93.9%; 95% CI, 80.4% -98.3%) in the prediction of MVI with an area under the receiver operating characteristic (ROC) curve of 0.763 (95% CI, 0.635-0.863).Conclusions: The findings indicated that arterial phase peritumoral enhancement on preoperative CECT and high serum PIVKA-II level were identified as potential predictors for MVI in cHCC-CCA patients.

Purpose Microvascular invasion (MVI) is a significant prognostic factor in combined hepatocellular cholangiocarcinoma (cHCC-CCA). However, its diagnosis relies on postoperative histopathologic analysis. This study aims to identify preoperative inflammatory biomarkers and MR-imaging features that can predict MVI in cHCC-CCA. Methods This retrospective study enrolled 119 patients with histopathologically confirmed cHCC-CCA between January 2016 and December 2021. Two radiologists, unaware of the clinical data, independently reviewed all MR image features. Univariable and multivariable analyses were performed to determine the independent predictors for MVI among inflammatory biomarkers and MRI characteristics. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic performance. Results Multivariable logistic regression analysis identified four variables significantly associated with MVI ( p < 0.05), including two inflammatory biomarkers [albumin-to-alkaline phosphatase ratio (AAPR) and aspartate aminotransferase-to-neutrophil ratio index (ANRI)] and two MRI features (non-smooth tumor margin and arterial phase peritumoral enhancement). A combined model for predicting MVI was constructed based on these four variables, with an AUC of 0.802 (95% CI 0.719–0.870). The diagnostic efficiency of the combined model was higher than that of the imaging model. Conclusion Inflammatory biomarkers and MRI features could be potential predictors for MVI in cHCC-CCA. The combined model, derived from inflammatory biomarkers and MRI features, showed good performance in preoperatively predicting MVI in cHCC-CCA patients. Graphical abstract

Abstract Background The study aimed to explore the value of CT findings and inflammatory indicators in differentiating benign and malignant gallbladder polypoid lesions before surgery. Methods The study comprised a total of 113 pathologically confirmed gallbladder polypoid lesions with a maximum diameter ≥ 1 cm (68 benign and 45 malignant), all of which were enhanced CT-scanned within 1 month before surgery. The CT findings and inflammatory indicators of the patients were analyzed by univariate and multivariate logistic regression analysis to identify independent predictors of gallbladder polypoid lesions, and then a nomogram distinguishing benign and malignant gallbladder polypoid lesions was developed by combining these characteristics. The receiver operating characteristic (ROC) curve and decision curve were plotted to assess the performance of the nomogram. Results Base status of the lesion (p < 0.001), plain CT value (p < 0.001), neutrophil–lymphocyte ratio (NLR) (p = 0.041), and monocyte-lymphocyte ratio (MLR) (p = 0.022) were independent predictors of malignant polypoid lesions of the gallbladder. The nomogram model established by incorporating the above factors had good performance in differentiating and predicting benign and malignant gallbladder polypoid lesions (AUC = 0.964), with sensitivity and specificity of 82.4% and 97.8%, respectively. The DCA demonstrated the important clinical utility of our nomogram. Conclusion CT findings combined with inflammatory indicators can effectively differentiate benign and malignant gallbladder polypoid lesions before surgery, which is valuable for clinical decision-making.

Objective:To summarize the clinical features, CT and MRI imaging findings of primary hepatic lymphoma(PHL), and investigate the diagnostic value of the imaging examination for PHL, so as to provide reliable basis for clinical diagnosis and treatment of PHL.Methods:A total of 15 patients with PHL confirmed by pathology and complete preoperative imaging data from January 2014 to December 2020 at Third Affiliated Hospital of Naval Medical University were retrospectively analyzed, including 8 cases with CT and 7 cases with MRI.The clinical features and imaging manifestations of PHL were analyzed.Results:All 15 patients with PHL had no specific clinical manifestations, 11 cases were single lesions and 4 cases were multiple lesions; 13 cases were mostly round, 8 cases had uniform density/signal; necrosis was seen in 7 cases; 9 cases showed progressive enhancement after enhancement scan, 7 of which were single nodules and 6 cases showed continuous enhancement. "Vascular floating sign" was seen in 11 cases, indicating no invasion of vessels.Conclusion:PHL is rare, and when the clinical presentation and laboratory diagnosis are not specific, the diagnosis of PHL should be considered when there is a single lesion in the liver with progressive enhancement and "vascular floating sign" on imaging.The diagnosis of PHL is suggested by the presence of multiple lesions with "vascular floating signs" .

PurposeThe present study aimed to develop and validate a preoperative model based on gadobenate-enhanced magnetic resonance imaging (MRI) for predicting microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) size of ≤5 cm. In order to provide preoperative guidance for clinicians to optimize treatment options.Methods164 patients with pathologically confirmed HCC and preoperative gadobenate-enhanced MRI from July 2016 to December 2020 were retrospectively included. Univariate and multivariate logistic regression (forward LR) analyses were used to determine the predictors of MVI and the model was established. Four-fold cross validation was used to verify the model, which was visualized by nomograms. The predictive performance of the model was evaluated based on discrimination, calibration, and clinical utility.ResultsElevated alpha-fetoprotein (HR 1.849, 95% CI: 1.193, 2.867, P=0.006), atypical enhancement pattern (HR 3.441, 95% CI: 1.523, 7.772, P=0.003), peritumoral hypointensity on HBP (HR 7.822, 95% CI: 3.317, 18.445, P<0.001), and HBP hypointensity (HR 3.258, 95% CI: 1.381, 7.687, P=0.007) were independent risk factors to MVI and constituted the HBP model. The mean area under the curve (AUC), sensitivity, specificity, and accuracy values for the HBP model were as follows: 0.830 (95% CI: 0.784, 0.876), 0.71, 0.78, 0.81 in training set; 0.826 (95% CI:0.765, 0.887), 0.8, 0.7, 0.79 in test set. The decision curve analysis (DCA) curve showed that the HBP model achieved great clinical benefits.ConclusionIn conclusion, the HBP imaging features of Gd-BOPTA-enhanced MRI play an important role in predicting MVI for HCC. A preoperative model, mainly based on HBP imaging features of gadobenate-enhanced MRI, was able to excellently predict the MVI for HCC size of ≤5cm. The model may help clinicians preoperatively assess the risk of MVI in HCC patients so as to guide clinicians to optimize treatment options.

Abstract Background Combined hepatocellular-cholangicarcinoma ( cHCC-CC) is a rare primary liver malignant tumor, the distinction between cHCC-CC and HCC before operation has important clinical significance for optimizing the treatment plan and predicting the prognosis of patients. This study intends to study the value of preoperative clinical date and enhanced MRI in the differential diagnosis of HCC and cHCC-CC and to obtain independent risk factors for predicting cHCC-CC. Methods The clinical and imaging data of 157 HCC and 59 cHCC-CC patients confirmed by pathology were collected, and the differences between the two groups of patients were compared by t test, chi-square test, and logistic regression analysis.Results CHCC-CC was more likely to show multiple lesions than HCC (28.81% Vs 10.83%，P=0.001) and more prone to microvascular invasion (MVI) (36.31%Vs 61.02%，P＜0.001). However, HCC had a higher incidence of liver cirrhosis than cHCC-CC (50.85% Vs72.61% ，P=0.003). The incidence of non-smooth margin was higher in cHCC-CC group (84.75% Vs52.23%，P＜0.001). The incidence of peritumor enhancement in arterial phase was higher in cHCC-CC group (11.46%Vs 62.71%，P＜0.001) Multivariate analysis showed that liver cirrhosis and arterial peritumor enhancement were independent risk factors for predicting cHCC-CC. In addition, the imaging sign of arterial phase peritumor enhancement had high sensitivity (62.71%) and specificity (88.54%) in the diagnosis of cHCC-CC.Conclusions Liver cirrhosis and the imaging findings of GD-DTPA-enhanced MRI are helpful for the differential diagnosis of HCC and cHCC-CC. In addition, the imaging sign of peritumoral enhancement in the arterial phase has high sensitivity and specificity for the diagnosis of cHCC-CC.

Background:The distinction between combined hepatocellular-cholangiocarcinoma (cHCC-CC) and hepatocellular carcinoma (HCC) before the operation has an important clinical significance for optimizing the treatment plan and predicting the prognosis of patients. Magnetic resonance imaging (MRI) has been widely used in the preoperative diagnosis and evaluation of primary liver malignant tumors. Purpose:The aim is to study the value of preoperative clinical data and enhanced MRI in the differential diagnosis of HCC and cHCC-CC and obtain independent risk factors for predicting cHCC-CC. Study type. Retrospective. Population. The clinical and imaging data of 157 HCC and 59 cHCC-CC patients confirmed by pathology were collected. Field Strength/Sequence. 1.5T; cross-sectional T1WI (gradient double echo sequence); cross-sectional T2WI (fast spin echo sequence, fat suppression); enhancement (3D LAVA technology). Assessment. The differences between the HCC and cHCC-CC patients were compared. Statistic Tests. Using the t-test, chi-square test, and logistic regression analysis, P < 0.05 was considered statistically significant. Result:1. CHCC-CC was more likely to show multiple lesions than HCC (28.81% vs. 10.83%, P = 0.001) and more prone to microvascular invasion (MVI) (36.31% vs. 61.02%, P < 0.001). However, HCC had a higher incidence of liver cirrhosis than cHCC-CC (50.85% vs. 72.61%, P = 0.003). 2. The incidence of nonsmooth margin was higher in the cHCC-CC group (84.75% vs. 52.23%, P < 0.001). The incidence of peritumor enhancement in the arterial phase was higher in the cHCC-CC group (11.46% vs. 62.71%, P < 0.001) 3. According to the multivariate analysis, arterial peritumor enhancement (OR = 8.833,95%CI:4.033,19.346, P < 0.001) was an independent risk factor for cHCC-CC (P < 0.001)). It had high sensitivity (62.71%) and specificity (88.54%) in the diagnosis of cHCC-CC. Date Conclusions. Liver cirrhosis and the imaging findings of GD-DTPA-enhanced MRI are helpful for the differential diagnosis of HCC and cHCC-CC. In addition, the imaging sign of peritumoral enhancement in the arterial phase has high sensitivity and specificity for the diagnosis of cHCC-CC.

Purpose The present study aimed to determine the reliable imaging features to distinguish atypical hepatocellular carcinoma (HCC) with peripheral rim-like enhancement from intrahepatic mass-forming cholangiocarcinoma (IMCC) on contrast-enhanced magnetic resonance imaging (MRI). Methods A total of 168 patients (130 male, 57.10 ± 10.53 years) pathological confirmed HCC or IMCC who underwent contrast-enhanced MRI between July 2019 and February 2022 were retrospectively included. Univariate and multivariate logistic regression analyses were used to determine independent differential factors for distinguishing HCC from IMCC, and the model was established. Bootstrap resampling 1000 times was used to verify the model, which was visualized by nomograms. The predictive performance of the model was evaluated based on discrimination, calibration, and clinical utility. Results Radiological capsule (OR 0.024, 95% CI: 0.006, 0.095, P<0.001), heterogeneous signal intensity (SI) on T1WI (OR 0.009, 95%CI: 0.001,0.056, P<0.001) were independent differential factors for predicting HCC over IMCC. A lobulated contour (OR 11.732, 95%CI: 2.928,47.007, P = 0.001), target sign on DP (OR 14.269, 95%CI: 2.849,82.106, P = 0.007), bile duct dilatation (OR 12.856, 95%CI: 2.013, P = 0.001) were independent differential factors for predicting IMCCs over HCCs. The independent differential factors constituted a model to distinguish atypical HCCs and IMCCs. The area under receiver operating characteristic (ROC) curve, sensitivity, and specificity values of the model were 0.964(0.940,0.987), 0.88, and 0.906, indicating that the model had an excellent differential diagnostic performance. The decision curve analysis (DCA) curve showed that the model obtained a better net clinical benefit. Conclusion The present study identified reliable imaging features for distinguishing atypical HCCs with peripheral rim-like enhancement from IMCCs on contrast-enhanced MRI. Our findings may help radiologists provide clinicians with more accurate preoperative imaging diagnoses to select appropriate treatment options.