Prognostic significance of MRI features in patients with solitary large hepatocellular carcinoma following surgical resection.

OBJECTIVE: To assess the prognostic impact of preoperative MRI features on outcomes for single large hepatocellular carcinoma (HCC) (≥ 8 cm) after surgical resection. MATERIAL AND METHODS: This retrospective study included 151 patients (mean age: 59.2 years; 126 men) with a single large HCC who underwent gadoxetic acid-enhanced MRI and surgical resection between 2008 and 2020. Clinical variables, including tumor markers and MRI features (tumor size, tumor margin, and the proportion of hypovascular component on hepatic arterial phase (AP) (≥ 50% vs. < 50% tumor volume) were evaluated. Cox proportional hazards model analyzed overall survival (OS), recurrence-free survival (RFS), and associated factors. RESULTS: Among 151 HCCs, 37.8% and 62.2% HCCs were classified as ≥ 50% and < 50% AP hypovascular groups, respectively. The 5- and 10-year OS and RFS rates in all patients were 62.0%, 52.6% and 41.4%, 38.5%, respectively. Multivariable analysis revealed that ≥ 50% AP hypovascular group (hazard ratio [HR] 1.7, p = 0.048), tumor size (HR 1.1, p = 0.006), and alpha-fetoprotein ≥ 400 ng/mL (HR 2.6, p = 0.001) correlated with poorer OS. ≥ 50% AP hypovascular group (HR 1.9, p = 0.003), tumor size (HR 1.1, p = 0.023), and non-smooth tumor margin (HR 2.1, p = 0.009) were linked to poorer RFS. One-year RFS rates were lower in the ≥ 50% AP hypovascular group than in the < 50% AP hypovascular group (47.4% vs 66.9%, p = 0.019). CONCLUSION: MRI with ≥ 50% AP hypovascular component and larger tumor size were significant factors associated with poorer OS and RFS after resection of single large HCC (≥ 8 cm). These patients require careful multidisciplinary management to determine optimal treatment strategies. CLINICAL RELEVANCE STATEMENT: Preoperative MRI showing a ≥ 50% arterial phase hypovascular component and larger tumor size can predict worse outcomes after resection of single large hepatocellular carcinomas (≥ 8 cm), underscoring the need for tailored, multidisciplinary treatment strategies. KEY POINTS: MRI features offer insights into the postoperative prognosis for large hepatocellular carcinoma. Hypovascular component on arterial phase ≥ 50% and tumor size predicted poorer overall survival and recurrence-free survival. These findings can assist in prioritizing aggressive and multidisciplinary approaches for patients at risk for poor outcomes.

Predictive Biomarkers for Immune-Checkpoint Inhibitor Treatment Response in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has one of the highest mortality rates among solid cancers. Late diagnosis and a lack of efficacious treatment options contribute to the dismal prognosis of HCC. Immune checkpoint inhibitor (ICI)-based immunotherapy has presented a new milestone in the treatment of cancer. Immunotherapy has yielded remarkable treatment responses in a range of cancer types including HCC. Based on the therapeutic effect of ICI alone (programmed cell death (PD)-1/programmed death-ligand1 (PD-L)1 antibody), investigators have developed combined ICI therapies including ICI + ICI, ICI + tyrosine kinase inhibitor (TKI), and ICI + locoregional treatment or novel immunotherapy. Although these regimens have demonstrated increasing treatment efficacy with the addition of novel drugs, the development of biomarkers to predict toxicity and treatment response in patients receiving ICI is in urgent need. PD-L1 expression in tumor cells received the most attention in early studies among various predictive biomarkers. However, PD-L1 expression alone has limited utility as a predictive biomarker in HCC. Accordingly, subsequent studies have evaluated the utility of tumor mutational burden (TMB), gene signatures, and multiplex immunohistochemistry (IHC) as predictive biomarkers. In this review, we aim to discuss the current state of immunotherapy for HCC, the results of the predictive biomarker studies, and future direction.

LI-RADS Version 2018 Targetoid Appearances on Gadoxetic Acid-Enhanced MRI: Interobserver Agreement and Diagnostic Performance for the Differentiation of HCC and Non-HCC Malignancy.

BACKGROUND. In LI-RADS version 2018, observations showing at least one of five targetoid appearances in different sequences or postcontrast phases are categorized LR-M, indicating likely non-hepatocellular carcinoma (HCC) malignancy. OBJECTIVE. The purpose of this study was to evaluate interobserver agreement for LI-RADS targetoid appearances among a large number of radiologists of varying experience and the diagnostic performance of targetoid appearances for differentiating HCC from non-HCC malignancy. METHODS. This retrospective study included 100 patients (76 men, 24 women; mean age, 58 ± 9 [SD] years) at high risk of HCC who underwent gadoxetic acid-enhanced MRI within 30 days before hepatic tumor resection (25 randomly included patients with non-HCC malignancy [13, intrahepatic cholangiocarcinoma; 12, combined HCC-cholangiocarcinoma]; 75 matched patients with HCC). Eight radiologists (four more experienced [8-15 years]; four less experienced [1-5 years]) from seven institutions independently assessed observations for the five targetoid appearances and LI-RADS categorization. Interobserver agreement and diagnostic performance for non-HCC malignancy were evaluated. RESULTS. Interobserver agreement was poor for peripheral washout (κ = 0.20); moderate for targetoid transitional phase or hepatobiliary phase appearance (κ = 0.33), delayed central enhancement (κ = 0.37), and targetoid restriction (κ = 0.43); and substantial for rim arterial phase hyperenhancement (κ = 0.61). Agreement was fair for at least one targetoid appearance (κ = 0.36) and moderate for at least two, three, or four targetoid appearances (κ = 0.43-0.51). Agreement for individual targetoid appearances was not significantly different between more experienced and less experienced readers other than for targetoid restriction (κ = 0.63 vs 0.43; p = .001). Agreement for at least one targetoid appearance was fair among more experienced (κ = 0.29) and less experienced (κ = 0.37) reviewers. Agreement for at least two, three, or four targetoid appearances was moderate to substantial among more experienced reviewers (κ = 0.45-0.63) and moderate among less experienced reviewers (κ = 0.42-0.56). Existing LR-M criteria of at least one targetoid appearance had median accuracy for non-HCC malignancy of 62%, sensitivity of 84%, and specificity of 54%. For all reviewers, accuracy was highest when at least three (median accuracy, 79%; sensitivity, 68%; specificity, 82%) or four (median accuracy, 80%; sensitivity, 54%; specificity, 88%) targetoid appearances were required. CONCLUSION. Targetoid appearances and LR-M categorization exhibited considerable interobserver variation among both more and less experienced reviewers. CLINICAL IMPACT. Requiring multiple targetoid appearances for LR-M categorization improved interobserver agreement and diagnostic accuracy for non-HCC malignancy.

Dual Oxidase 2 (DUOX2) as a Proteomic Biomarker for Predicting Treatment Response to Chemoradiation Therapy for Locally Advanced Rectal Cancer: Using High-Throughput Proteomic Analysis and Machine Learning Algorithm.

High-throughput mass-spectrometry-based quantitative proteomic analysis was performed using formalin-fixed, paraffin-embedded (FFPE) biopsy samples obtained before treatment from 13 patients with locally advanced rectal cancer (LARC), who were treated with concurrent chemoradiation therapy (CCRT) followed by surgery. Patients were divided into complete responder (CR) and non-complete responder (nCR) groups. Immunohistochemical (IHC) staining of 79 independent FFPE tissue samples was performed to validate the predictive ability of proteomic biomarker candidates. A total of 3637 proteins were identified, and the expression of 498 proteins was confirmed at significantly different levels (differentially expressed proteins-DEPs) between two groups. In Gene Ontology enrichment analyses, DEPs enriched in biological processes in the CR group included proteins linked to cytoskeletal organization, immune response processes, and vesicle-associated protein transport processes, whereas DEPs in the nCR group were associated with biosynthesis, transcription, and translation processes. Dual oxidase 2 (DUOX2) was selected as the most predictive biomarker in machine learning algorithm analysis. Further IHC validation ultimately confirmed DUOX2 as a potential biomarker for predicting the response of nCR to CCRT. In conclusion, this study suggests that the treatment response to RT may be affected by the pre-treatment tumor microenvironment. DUOX2 is a potential biomarker for the early prediction of nCR after CCRT.

Effect of Microvascular Invasion Risk on Early Recurrence of Hepatocellular Carcinoma After Surgery and Radiofrequency Ablation.

OBJECTIVE: We compared surgical resection (SR) and radiofrequency ablation (RFA) as first-line treatment in patients with hepatocellular carcinoma (HCC) based on the risk of microvascular invasion (MVI). BACKGROUND: The best curative treatment modality between SR and RFA in patients with HCC with MVI remains unclear. METHODS: Data from 2 academic cancer center-based cohorts of patients with a single, small (≤3 cm) HCC who underwent SR were used to derive (n = 276) and validate (n = 101) prediction models for MVI using clinical and imaging variables. The MVI prediction model was developed using multivariable logistic regression analysis and externally validated. Early recurrence (<2 years) based on risk stratification between SR (n = 276) and RFA (n = 240) was evaluated via propensity score matching. RESULTS: In the multivariable analysis, alpha-fetoprotein (≥15 ng/mL), protein induced by vitamin K absence-II (≥48 mAU/mL), arterial peritumoral enhancement, and hepatobiliary peritumoral hypointensity on magnetic resonance imaging were associated with MVI. Incorporating these factors, the area under the receiver operating characteristic curve of the predictive model was 0.87 (95% confidence interval: 0.82-0.92) and 0.82 (95% confidence interval: 0.74-0.90) in the derivation and validation cohorts, respectively. SR was associated with a lower rate of early recurrence than RFA based on the risk of MVI after propensity score matching (P < 0.05). CONCLUSIONS: Our model predicted the risk of MVI in patients with a small (≤ 3 cm) HCC with high accuracy. Patients with MVI who had undergone RFA were more vulnerable to recurrence than those who had undergone SR.

Tumor Budding as a Prognostic Marker in Rectal Cancer Patients on Propensity Score Analysis.

BACKGROUND: Tumor budding is associated with adverse histology. It is a predictor of poor oncologic outcomes in colorectal cancer. However, it remains unclear whether tumor budding is a predictor of poor prognosis for rectal cancer patients regardless of neoadjuvant chemoradiotherapy (nCRT). PATIENTS AND METHODS: This study analyzed 2888 rectal cancer patients who underwent radical surgery from 2007 to 2014. Among these patients, 939 underwent nCRT while 1949 did not receive nCRT. Tumor budding was defined as positive if the number of isolated tumor cells or small clusters of up to five tumor cells at the invasive front of the tumor was five or more. If the number was less than five, it was defined as negative. Patients were categorized according to tumor budding status. We used 1:1 propensity score matching to adjust for potential baseline confounders between the two groups. RESULTS: Among 2888 patients, 939 received nCRT while 1949 did not receive nCRT. A total of 418 patients who received nCRT were matched (209 in each group). A total of 1024 patients without nCRT were also matched (512 in each group). In matched patients, 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates for the positive budding group were significantly lower than those in the negative budding group regardless of nCRT. On multivariate analysis of prognostic factors, positive budding was associated with poorer disease-free survival independent of nCRT. CONCLUSION: Tumor budding positivity is a prognostic indicator of poor outcomes in rectal cancer patients regardless of neoadjuvant chemoradiotherapy.

Vanishing washout of hepatocellular carcinoma according to the presence of hepatic steatosis: diagnostic performance of CT and MRI.

OBJECTIVES: To compare the presence of washout and the diagnostic performance of computed tomography (CT) and magnetic resonance imaging (MRI) for hepatocellular carcinoma (HCC) according to the presence of hepatic steatosis. METHODS: This retrospective study included 566 patients with chronic liver disease who had undergone hepatic resection for hepatic tumors (482 HCCs and 84 non-HCCs) between January 2016 and June 2018 and had available multiphasic CT and MR images. Patients were allocated in the fatty liver (n = 141) or non-fatty liver (n = 425) group according to the presence of hepatic steatosis, defined as lipid droplets in at least 5% of hepatocytes on pathological examination. The presence of HCC washout and the diagnostic performance of CT and MRI for HCC were compared between the groups. RESULTS: HCC washout was less frequently seen in the fatty liver group than in the non-fatty liver group on CT (61.5% vs. 88.9%, p < 0.001), whereas it was similarly present on MRI in both groups (77.0% vs. 74.4%, p = 0.565). For diagnosis of HCC, the sensitivity (53.3% vs. 80.0%, p < 0.001) and accuracy (53.9% vs. 80.9%, p < 0.001) of CT were lower in the fatty liver group than in the non-fatty liver group. However, for MRI, these values were not significantly different between the groups (p > 0.05). CONCLUSIONS: Hepatic steatosis significantly decreased the performance of CT for the diagnosis of HCC, whereas it did not significantly alter the performance of MRI. KEY POINTS: • Unlike MRI, there is vanishing HCC washout on CT caused by the background hepatic steatosis. • The diagnostic performance of CT for the diagnosis of HCC was significantly altered by hepatic steatosis. • The optimal cutoff HU value of the liver parenchyma for the vanishing washout of HCC was < 50 HU on unenhanced CT images.

Prognostic value of LI-RADS category on gadoxetic acid-enhanced MRI and 18F-FDG PET-CT in patients with primary liver carcinomas.

OBJECTIVES: To evaluate the postoperative prognostic value of the Liver Imaging Reporting and Data System (LI-RADS) category on gadoxetic acid-enhanced MRI and 18F-fluorodeoxyglucose PET-CT in patients with primary liver carcinomas (PLCs). METHODS: A total of 189 patients with chronic liver disease and surgically proven single PLC (42 intrahepatic cholangiocarcinomas and 21 combined hepatocellular-cholangiocarcinomas and 126 hepatocellular carcinomas [2:1 matching to non-HCC malignancies]) were retrospectively evaluated with gadoxetic acid-enhanced MRI and PET-CT. Two independent reviewers assigned an LI-RADS category for each observation. The tumor-to-liver standardized uptake value ratio (TLR) was calculated. The overall survival (OS), recurrence-free survival (RFS), and the associated factors were evaluated. RESULTS: In multivariable analysis, LI-RADS category (LR-4 or LR-5 [LR-4/5] vs. LR-M; OS, hazard ratio [HR] 2.24, p = 0.006; RFS, HR 1.61, p = 0.028) and TLR (low, < 2.3 vs. high, ≥ 2.3; OS, HR 2.09, p = 0.014; RFS, HR 2.17, p < 0.001) were the independent factors for OS and RFS. For the LR-M group, the high TLR group showed lower OS and RFS rates than the low TLR group (OS, p = 0.008; RFS, p < 0.001). For the LR-4/5 group, the OS and RFS rates were not significantly different between the high TLR and low TLR groups (both p > 0.05). CONCLUSIONS: Both LI-RADS category on MRI and TLR on PET-CT are associated with the postoperative prognosis of PLCs. The prognosis of PLCs classified as LR-M can be further stratified according to the TLR group, but not for the PLCs classified as LR-4/5. KEY POINTS: • The LI-RADS category (LR-4/5 vs. LR-M) and tumor-to-liver standardized uptake value ratio (TLR, low vs. high) were independent factors for postoperative prognosis of primary liver carcinomas (PLCs). • For PLCs classified as LR-M, the TLR group helps stratify the postoperative prognosis of PLCs, with the high TLR group having a poor prognosis and the low TLR group having a better prognosis (p = 0.008 for OS and p < 0.001 for RFS). • For PLCs classified as LR-4/5, the OS and RFS rates were not significantly different between the high TLR and low TLR groups (both p > 0.05).

Comparison of ablation performance between dual internally cooled wet tip and conventional dual internally cooled tip radiofrequency electrodes: an experimental study in ex vivo bovine liver.

OBJECTIVE: To evaluate the performance of dual internally cooled wet tip (ICWT) radiofrequency electrodes in comparison to dual internally cooled tip (ICT) electrodes. METHODS: Twenty ablation zones were created for each type of electrodes. Planned procedure time was 6 min. Diameters of the ablation zone along the x-, y-, and z-axes (Dx, Dy, and Dz), ablation zone sphericity, quantitative sphericity measurement, and ablation volume were measured and compared between the two electrode types. Circularity of the ablation zone on the surface with x- and z- axes (zx plane) and amount of energy applied were also compared. RESULTS: Dx and Dz were significantly longer with ICWT than those with ICT (Dx: 3.0 vs. 2.8 cm, p = .018; and Dz: 2.7 vs. 2.3 cm, p < .001, respectively). Dy was not significantly different (3.0 vs. 2.9 cm, p = .220). Moreover, 85% (17/20) and 30% (6/20) of ablation zones from ICWT and ICT were spherical (p = .001), respectively. Quantitative measurement showed that ICWT was more spherical compared to ICT (0.962 vs. 0.881, p = .001). The ablation volume was also significantly higher with ICWT (11.55 vs. 9.45 cm3, p = .003). The ablation zone on the zx plane was more circular with ICWT (0.907 vs. 0.883, p = .028). The amount of energy applied was significantly bigger with ICWT (18508 vs. 16998 WS, p = .003). CONCLUSION: Dual ICWT electrodes were better able to create more spherical and larger ablation zones than dual ICT electrodes.

Interobserver Variability and Diagnostic Performance of Gadoxetic Acid-enhanced MRI for Predicting Microvascular Invasion in Hepatocellular Carcinoma.

Background Accurate identification of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) before treatment is critical for selecting a proper treatment strategy. Purpose To evaluate the interobserver agreement and the diagnostic performance of the MRI assessment of MVI in HCC according to the level of radiologist experience. Materials and Methods This retrospective study included 100 patients with surgically confirmed HCCs smaller than 5 cm who underwent gadoxetic acid-enhanced MRI between 2013 and 2016. Eight postfellowship radiologists (four with 7-13 years of experience [more experienced] and four with 3-6 years of experience [less experienced]) evaluated four imaging features (nonsmooth tumor margin, irregular rim-like enhancement in the arterial phase, peritumoral arterial phase hyperenhancement, peritumoral hepatobiliary phase hypointensity) and assigned the possibility of MVI. Interobserver agreement was determined by using Fleiss κ statistics according to reviewer experience and tumor size (≤3 cm vs >3 cm). With reference standards of histopathologic specimens, the diagnostic performance in the identification of MVI was assessed by using receiver operating characteristic curve analysis. Results In 100 patients (mean age, 58 years ± 10 [standard deviation]; 70 men) with 100 HCCs (mean size, 2.8 cm ± 0.9), 39 (39%) HCCs had MVI. The overall interobserver agreement was fair to moderate for the imaging features and their combinations (κ = 0.38-0.47) and MVI probability (κ = 0.41; 95% confidence interval: 0.33, 0.45). More experienced reviewers demonstrated higher agreement in MVI probability than less experienced reviewers (κ = 0.55 vs 0.36, respectively; P = .002). Diagnostic performance of each reviewer was modest for MVI prediction (area under the receiver operating characteristic curve [AUC] range, 0.60-0.74). The AUCs for the diagnosis of MVI were lower for HCCs larger than 3 cm (range, 0.55-0.69) than for those less than or equal to 3 cm (range, 0.59-0.75). Conclusion Considerable interobserver variability exists in the assessment of microvascular invasion in hepatocellular carcinoma using MRI, even for more experienced radiologists. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Tang in this issue.

Radiologic-Pathologic Correlation of Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement at Gadoxetic Acid-enhanced MRI: A Multicenter Study.

Background Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) at gadoxetic acid-enhanced MRI may indicate hepatocellular carcinoma (HCC) or nonmalignant cirrhosis-associated nodules. Purpose To assess the distribution of pathologic diagnoses of HBP hypointense nodules without APHE at gadoxetic acid-enhanced MRI and to evaluate clinical and imaging features in differentiating their histologic grades. Materials and Methods This retrospective multicenter study included pathologic analysis-confirmed HBP hypointense nodules without APHE (≤30 mm) in patients with chronic liver disease or cirrhosis screened between January 2008 and June 2016. Central pathologic review by 10 pathologists determined final histologic grades as progressed HCC, early HCC, high-grade dysplastic nodule (DN), and low-grade DN or regenerative nodule. Gadoxetic acid-enhanced MRI features were analyzed by three radiologists. Multivariable logistic regression analyses with elastic net regularization were performed to identify clinical and imaging features for differentiating histologic grades. Results There were 298 patients (mean age, 59 years ± 10; 226 men) with 334 nodules evaluated, and progressed HCCs were diagnosed in 44.0% (147 of 334), early HCCs in 20.4% (68 of 334), high-grade DNs in 27.5% (92 of 334), and low-grade DNs or regenerative nodules in 8.1% (27 of 334). Serum α-fetoprotein level 100 ng/mL or greater (odds ratio, 2.7; P = .01) and MRI features including well-defined margin (odds ratio, 5.5; P = .003), hypointensity at precontrast T1-weighted imaging (odds ratio, 3.2; P < .001), intermediate hyperintensity at T2-weighted imaging (odds ratio, 3.4; P < .001), and restricted diffusion (odds ratio, 1.9; P = .04) were independent predictors for progressed HCC at multivariable analysis. Conclusion In patients at high risk for hepatocellular carcinoma (HCC), hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid-enhanced MRI corresponded mainly to progressed HCCs, early HCCs, and high-grade dysplastic nodules. High α-fetoprotein level and some imaging features at MRI helped to differentiate progressed HCC from lower grade nodules. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Motosugi in this issue.

Deep learning with ultrasonography: automated classification of liver fibrosis using a deep convolutional neural network.

OBJECTIVES: The aim of this study was to develop a deep convolutional neural network (DCNN) for the prediction of the METAVIR score using B-mode ultrasonography images. METHODS: Datasets from two tertiary academic referral centers were used. A total of 13,608 ultrasonography images from 3446 patients who underwent surgical resection, biopsy, or transient elastography were used for training a DCNN for the prediction of the METAVIR score. Pathological specimens or estimated METAVIR scores derived from transient elastography were used as a reference standard. A four-class model (F0 vs. F1 vs. F23 vs. F4) was developed. Diagnostic performance of the algorithm was validated on a separate internal test set of 266 patients with 300 images and external test set of 572 patients with 1232 images. Performance in classification of cirrhosis was compared between the DCNN and five radiologists. RESULTS: The accuracy of the four-class model was 83.5% and 76.4% on the internal and external test set, respectively. The area under the receiver operating characteristic curve (AUC) for classification of cirrhosis (F4) was 0.901 (95% confidence interval [CI], 0.865-0.937) on the internal test set and 0.857 (95% CI, 0.825-0.889) on the external test set, respectively. The AUC of the DCNN for classification of cirrhosis (0.857) was significantly higher than that of all five radiologists (AUC range, 0.656-0.816; p value < 0.05) using the external test set. CONCLUSIONS: The DCNN showed high accuracy for determining METAVIR score using ultrasonography images and achieved better performance than that of radiologists in the diagnosis of cirrhosis. KEY POINTS: • DCNN accurately classified the ultrasonography images according to the METAVIR score. • The AUROC of this algorithm for cirrhosis assessment was significantly higher than that of radiologists. • DCNN using US images may offer an alternative tool for monitoring liver fibrosis.

Pre-operative ADC predicts early recurrence of HCC after curative resection.

OBJECTIVES: To assess a correlation between the preoperative diffusion-weighted imaging (DWI) and early recurrence (<2 years) and to determine the best DWI parameters as the risk factor of early recurrence after surgery in single hepatocellular carcinoma (HCC). METHODS: The study included 114 patients with surgically resected single HCC (≤5 cm) who underwent preoperative magnetic resonance imaging (MRI) with DWI. Radiologists evaluated the diffusion restriction of the tumours using qualitative assessment and the mean and minimum apparent diffusion coefficient values (ADCmean and ADCmin) of the tumours using quantitative measurement. Clinical and laboratory findings and DWI parameters as a risk factor for early recurrence were identified by using Cox proportional hazards model. RESULTS: No significant difference was observed in early recurrence rates of HCCs between those with and those without diffusion restriction (p = 0.484). Early recurrence rates of HCCs with ADCmean and ADCmin values lower than the optimal cut-offs (1.023 and 0.773 × 10-3 mm2/s, respectively) were significantly higher compared with those with values higher than the optimal cut-offs (p = 0.001 and p < 0.001, respectively). In the multivariable analysis, tumour size [hazard ratio (HR) per centimetre, 2.011; 95% CI, 1.304-3.102; p = 0.002] and ADCmin ≤0.773 × 10-3 mm2/s (HR, 13.339; 95% CI, 4.422-40.240; p < 0.001) were independent risk factors for early HCC recurrence. CONCLUSIONS: DWI is a promising imaging tool for early recurrence of HCC. Among qualitative and quantitative assessments of DWI, ADCmin is a significant risk factor for early recurrence after surgery in single HCC. KEY POINTS: • The performance of minimum apparent diffusion coefficient (ADCmin) is significantly better than that of mean apparent diffusion coefficient (ADCmean) for identifying early recurrence. • ADCmin is a significantly independent risk factor of early HCC recurrence after surgery. • ADCmin correlates with early recurrence after curative resection of single HCC, reflecting histopathological features of the tumours including histological grade and microvascular invasion.

Differentiation of Hepatic Sclerosed Hemangiomas From Cavernous Hemangiomas Based on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging Features.

OBJECTIVE: The objective of this study was to evaluate the imaging features of a hepatic sclerosed hemangioma by comparing them with those of a cavernous hemangioma using magnetic resonance imaging with gadoxetic acid enhancement. METHODS: Nine patients with hepatic sclerosed hemangiomas and 36 patients with cavernous hemangiomas (control group) who underwent gadoxetic acid-enhanced magnetic resonance imaging were included. Qualitative values (imaging findings and enhancement pattern [typical vs atypical enhancement]) and quantitative values (apparent diffusion coefficient) were evaluated. RESULTS: Patients with sclerosed hemangiomas showed significantly more irregular tumor margin on hepatobiliary phase images, peritumoral arterial enhancement, and a lower proportion of hyperintensity on heavily T2-weighted images compared with controls (all P values <0.05). In addition, the sclerosed hemangioma group had significantly more frequent atypical enhancement patterns than did the control group (88.9% vs 33.3%; P = 0.006). However, the mean apparent diffusion coefficient value of hemangiomas was not significantly different between the 2 groups (P = 0.639). CONCLUSIONS: Gadoxetic acid-enhanced magnetic resonance images can help in differentiating between hepatic sclerosed hemangiomas and cavernous hemangiomas.

Hepatobiliary MRI as novel selection criteria in liver transplantation for hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatobiliary magnetic resonance imaging (MRI) provides additional information beyond the size and number of tumours, and may have prognostic implications. We examined whether pretransplant radiological features on MRI could be used to stratify the risk of tumour recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC). METHODS: A total of 100 patients who had received a liver transplant and who had undergone preoperative gadoxetic acid-enhanced MRI, including the hepatobiliary phase (HBP), were reviewed for tumour size, number, and morphological type (e.g. nodular, nodular with perinodular extension, or confluent multinodular), satellite nodules, non-smooth tumour margins, peritumoural enhancement in arterial phase, peritumoural hypointensity on HBP, and apparent diffusion coefficients. The primary endpoint was time to recurrence. RESULTS: In a multivariable adjusted model, the presence of satellite nodules [hazard ratio (HR) 3.07; 95% confidence interval (CI) 1.14-8.24] and peritumoural hypointensity on HBP (HR 4.53; 95% CI 1.52-13.4) were identified as independent factors associated with tumour recurrence. Having either of these radiological findings was associated with a higher tumour recurrence rate (72.5% vs. 15.4% at three years, p <0.001). When patients were stratified according to the Milan criteria, the presence of these two high-risk radiological findings was associated with a higher tumour recurrence rate in both patients transplanted within the Milan criteria (66.7% vs. 11.6% at three years, p <0.001, n = 68) and those who were transplanted outside the Milan criteria (75.5% vs. 28.6% at three years, p <0.001, n = 32). CONCLUSIONS: Radiological features on preoperative hepatobiliary MRI can stratify the risk of tumour recurrence in patients who were transplanted either within or outside the Milan criteria. Therefore, hepatobiliary MRI can be a useful way to select potential candidates for LT. LAY SUMMARY: High-risk radiological findings on preoperative hepatobiliary magnetic resonance imaging (either one of the following features: satellite nodule and peritumoural hypointensity on hepatobiliary phase) were associated with a higher tumour recurrence rate in patients transplanted either within or outside the Milan criteria.

Prognostic Impact of Tumor-Budding Grade in Stages 1-3 Colon Cancer: A Retrospective Cohort Study.

BACKGROUND: Tumor budding is associated with adverse histology and is a predictor of lymph node metastasis. However, it remains unclear whether tumor budding is predictive of a poor prognosis for colon cancer patients. This study sought to investigate the prognostic significance of tumor budding in colon cancer. METHODS: This study evaluated 4196 colon cancer patients who underwent radical surgery from 2007 to 2013 at a single institution. The patients were categorized according to tumor-budding status. Adjustment was made for using propensity score-matched analysis, and both disease-free survival (DFS) and overall survival (OS) were compared between the groups. RESULTS: Among the 4196 patients, 2269 had low budding (< 5 buds), 1312 had intermediate budding (5-9 buds), and 615 had high budding (≥ 10 buds). High budding was associated with adverse histologic features such as elevated levels of preoperative carcinoembryonic antigen, advanced stage, poor histology, and the presence of lymphatic/vascular/perineural invasion. Before matching, DFS and OS decreased significantly with increasing tumor budding. After matching, the difference in survival between the low- and intermediate-budding groups disappeared. However, the OS and DFS rates for the high-budding group were significantly lower than for the other two groups. In the multivariate analysis of prognostic factors, high budding was an independent poor prognostic factor in DFS and OS, whereas tumor-budding positivity itself was not an independent prognostic factor. CONCLUSION: Tumor-budding grade rather than tumor-budding positivity was an independent prognostic factor in colon cancer.

Hepatic neuroendocrine tumour: Apparent diffusion coefficient as a potential marker of prognosis associated with tumour grade and overall survival.

OBJECTIVES: To evaluate the correlation between grade of hepatic neuroendocrine tumours (NETs) according to the 2010 World Health Organization (WHO) classification and the apparent diffusion coefficient (ADC) and to assess whether ADC value can predict overall survival (OS) after diagnosis of hepatic NETs. METHODS: The study included 63 patients who underwent magnetic resonance (MR) imaging with diffusion-weighted images for the evaluation of hepatic NETs. The correlation between qualitative and quantitative MR imaging findings, including ADC values, and WHO classifications was assessed. The association between ADC value and OS was analyzed. RESULTS: The ADC values and WHO classification of hepatic NETs were moderately negatively correlated in a statistically significant manner (ρ = -0.57, p < 0.001). The OS rates were significantly different according to the ADC value (low ADC vs. high ADC, p = 0.006) as well as WHO classifications (G1+ G2 vs. G3, p = 0.038). However, multivariate analysis revealed that the only independent predictor for OS was a low ADC value (hazard ratio: 3.37, p = 0.010). CONCLUSION: There was a significant correlation between the ADC value of hepatic NETs and the WHO tumour grade. Additionally, the ADC value of a hepatic NET might be more accurate than the current WHO tumour grade for predicting OS. KEY POINTS: • ADC values of hepatic NET and WHO tumour grade were negatively correlated. • Lower ADC values of hepatic NET were significantly correlated with worse OS. • ADC value might be more accurate than WHO grade for predicting OS.

Identification of risk factors for sessile and traditional serrated adenomas of the colon by using big data analysis.

BACKGROUND AND AIM: Little is known about the risk factors associated with serrated polyps, because the early studies, which occurred before the new World Health Organization classification was introduced, included mixtures of serrated polyps. This study aimed to evaluate the risk factors associated with the presence of sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs) using big data analytics. METHODS: Using a case-control design, we evaluated the risk factors associated with the presence of SSAs and TSAs. Subjects who underwent colonoscopies from 2002 to 2012 as part of the comprehensive health screening programs undertaken at the Samsung Medical Center, Korea, participated in this study. RESULTS: Of the 48 677 individuals who underwent colonoscopies, 183 (0.4%) had SSAs and 212 (0.4%) had TSAs. The multivariate analysis determined that being aged ≥ 50 years (odds ratio [OR] 1.91, 95% confidential interval [CI] 1.27-2.90, P = 0.002) and a history of colorectal cancer among first-degree relatives (OR 3.14, 95% CI 1.57-6.27, P = 0.001) were significant risk factors associated with the presence of SSAs and that being aged ≥ 50 years (OR 2.61, 95% CI 1.79-3.80, P < 0.001), obesity (OR 1.63, 95% CI 1.12-2.36, P = 0.010), and a higher triglyceride level (OR 1.63, 95% CI 1.12-2.36, P = 0.010) were independent risk factors associated with the presence of TSAs. CONCLUSIONS: We used big data analytics to determine the risk factors associated with the presence of specific polyp subgroups, and individuals who have these risk factors should be carefully scrutinized for the presence of SSAs or TSAs during screening colonoscopies.

Hepatocellular carcinoma with central scar on gadoxetic acid-enhanced and diffusion-weighted magnetic resonance imaging.

Background Central scars are rarely reported in conventional hepatocellular carcinoma (HCC). The presence of central scars on imaging might lead to erroneous diagnosis of hepatic tumors. Purpose To determine imaging features of HCC with central scars on magnetic resonance imaging (MRI) including gadoxetic acid-enhanced and diffusion-weighted imaging (DWI). Material and Methods Fifty-one patients with 51 surgically confirmed HCCs with central scars (fibrotic scar: n = 50; myxoid scar: n = 1; range = 1.2-15 cm; mean = 3.7 cm) underwent liver MRI that consisted of T1- and T2-weighted (T2W) imaging, gadoxetic acid-enhanced arterial, portal, 3-min late phase, and 20-min hepatobiliary phase (HBP), and DWI. Two reviewers evaluated morphology, signal intensity, and enhancement features of tumors and central scars for each image and reached consensus. Results Lobulated contour was seen for 30 tumors (58.8%); the rest were round or oval masses. Central scars (range = 0.2-6.0 cm; mean = 0.9 cm) were most commonly seen as defects within hyperenhancement on arterial phase images (n = 47, 92.2%), bright (n = 28, 54.9%) or dark areas (n = 15, 29.4%) on T2W imaging, areas of central darkness on high b-value DWI (b = 800) (n = 31, 60.8%), and/or central enhancement on HBP (n = 36, 70.6%), mimicking a target appearance. Tumor capsule was seen in 35 (39 pathology, 74.5%) and intratumoral septum in 35 (41 pathology, 78.4%) tumors on gadoxetic acid-enhanced MRI. Conclusion Non-fibrolamellar HCC may show central scar. HCC with central scar mimics cholangiocarcinoma by showing a target appearance on HBP and DWI. Tumor capsule and intratumoral septum might be useful for characterizing HCC with central scar.

Tumefactive Gallbladder Sludge at US: Prevalence and Clinical Importance.

Purpose To evaluate the prevalence of tumefactive sludge of the gallbladder detected at ultrasonography (US) and to assess whether any clinical and imaging differences exist between benign and malignant tumefactive sludge. Materials and Methods The institutional review board approved this retrospective study. The requirement for informed consent was waived. The study included a cohort (n = 6898) of patients with gallbladder sludge drawn from all adults (n = 115 178) who underwent abdominal US between March 2001 and March 2015. Tumefactive sludge was identified according to the following US findings: (a) nonmovable mass-like lesion and (b) absence of posterior acoustic shadowing at B-mode US and vascularity at color Doppler US. Follow-up examinations were arranged to ascertain whether the results showed true sludge or gallbladder cancer. Risk factors for malignant tumefactive sludge based on clinical and US characteristics were identified with multivariate logistic regression analysis. Results The prevalence of gallbladder and tumefactive sludge at abdominal US during the observation period was 6.0% (6898 of 115 178) and 0.1% (135 of 115 178), respectively. Twenty-eight (20.7%) patients were lost to follow-up. Of the 107 with tumefactive sludge, 15 (14%) were confirmed to have malignant tumefactive sludge. The risk factors for malignant tumefactive sludge were old age (odds ratio [OR], 1.06; P = .035), female sex (OR, 5.48; P = .014), and absence of hyperechoic spots within the sludge (OR, 6.78; P = .008). Conclusion Although the prevalence of tumefactive sludge at US was rare, a considerable proportion of patients had a malignancy. Careful follow-up is essential, especially for older patients, women, and those with an absence of hyperechoic spots at US. © RSNA, 2016 Online supplemental material is available for this article.