TAAR8 Mediates Increased Migrasome Formation by Cadaverine in RPE Cells.

Migrasomes, the newly discovered cellular organelles that form large vesicle-like structures on the retraction fibers of migrating cells, are thought to be involved in communication between neighboring cells, cellular content transfer, unwanted material shedding, and information integration. Although their formation has been described previously, the molecular mechanisms of migrasome biogenesis are largely unknown. Here, we developed a cell line that overexpresses GFP-tetraspanin4, enabling observation of migrasomes. To identify compounds that regulate migrasome activity in retinal pigment epithelial (RPE) cells, we screened a fecal chemical library and identified cadaverine, a biogenic amine, as a potent migrasome formation inducer. Compared with normal migrating cells, those treated with cadaverine had significantly more migrasomes. Putrescine, another biogenic amine, also increased migrasome formation. Trace amine-associated receptor 8 (TAAR8) depletion inhibited migrasome increase in cadaverine-treated RPE cells, and cadaverine also inhibited protein kinase A phosphorylation. In RPE cells, cadaverine triggers migrasome formation via a TAAR8-mediated protein kinase A signaling pathway.

Comparison of non-contrast abbreviated MRI and ultrasound as surveillance modalities for HCC.

BACKGROUND & AIMS: Ultrasound (US) is recommended for HCC surveillance in high-risk patients but has limited performance in detecting early-stage HCC. We aimed to compare the diagnostic performance of biannual US and annual non-contrast abbreviated magnetic resonance imaging (NC-AMRI) as HCC surveillance modalities in high-risk patients. METHODS: This prospective, multicenter cohort study enrolled participants with an estimated annual risk of HCC greater than 5% between October 2015 and April 2017. Participants underwent six rounds of HCC surveillance at 6-month intervals, with both US and NC-AMRI at rounds 1, 3, and 5, and only US at rounds 2, 4, and 6. The sensitivity, diagnostic yield (DY), and false referral rate (FRR) for HCC detection by US and NC-AMRI were compared. RESULTS: In total, 208 participants underwent 980 US and 516 NC-AMRI examinations during 30 months of follow-up. Among them, 34 HCCs were diagnosed in 31 participants, with 20 (64.5%) classified as very early-stage and 11 (35.5%) as early-stage HCC. The sensitivity of annual NC-AMRI (71.0%, 22/31) was marginally higher than that of biannual US (45.2%, 14/31; p = 0.077). NC-AMRI showed a significantly higher DY than US (4.26% vs. 1.43%, p <0.001), with a similar FRR (2.91% vs. 3.06%, p = 0.885). A simulation of alternating US and NC-AMRI at 6-month intervals yielded a sensitivity of 83.9% (26/31), significantly exceeding that of biannual US (p = 0.006). CONCLUSIONS: Annual NC-AMRI showed a marginally higher sensitivity than biannual US for HCC detection in high-risk patients. The DY of annual NC-AMRI was significantly higher than that of biannual US, without increasing the FRR. Thus, alternating US and NC-AMRI at 6-month intervals could be an optimal surveillance strategy for high-risk patients. IMPACT AND IMPLICATIONS: Current guidelines permit the use of magnetic resonance imaging (MRI) as a surveillance tool for hepatocellular carcinoma in patients in whom ultrasonography (US) is inadequate. However, the specific indications, imaging sequences, and intervals for MRI surveillance remain unclear. In our study, we found that annual non-contrast abbreviated MRI exhibited marginally higher sensitivity and significantly better diagnostic yield than biannual US in patients at high risk of hepatocellular carcinoma. Alternating US and non-contrast abbreviated MRI at 6-month intervals led to significantly improved sensitivity compared to biannual US, making it a potentially optimal surveillance strategy for high-risk patients. GOV IDENTIFIER: NCT02551250.

Postnatal growth restriction alters myocardial mitochondrial energetics in mice.

Postnatal growth restriction (PGR) can increase the risk of cardiovascular disease (CVD) potentially due to impairments in oxidative phosphorylation (OxPhos) within cardiomyocyte mitochondria. The purpose of this investigation was to determine if PGR impairs cardiac metabolism, specifically OxPhos. FVB (Friend Virus B-type) mice were fed a normal-protein (NP: 20% protein), or low-protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce ∼20% less milk, and pups nursed by LP dams experience reduced growth into adulthood as compared to pups nursed by NP dams. At birth (PN1), pups born to dams fed the NP diet were transferred to LP dams (PGR group) or a different NP dam (control group: CON). At weaning (PN21), all mice were fed the NP diet. At PN22 and PN80, mitochondria were isolated for respirometry (oxygen consumption rate, J O 2 ${J_{{{\mathrm{O}}_{\mathrm{2}}}}}$ ) and fluorimetry (reactive oxygen species emission, J H 2 O 2 ${J_{{{\mathrm{H}}_{\mathrm{2}}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) analysis measured as baseline respiration (LEAK) and with saturating ADP (OxPhos). Western blotting at PN22 and PN80 determined protein abundance of uncoupling protein 3, peroxiredoxin-6, voltage-dependent anion channel and adenine nucleotide translocator 1 to provide further insight into mitochondrial function. ANOVAs with the main effects of diet, sex and age with α-level of 0.05 was set a priori. Overall, PGR (7.8 ± 1.1) had significant (P = 0.01) reductions in respiratory control in complex I when compared to CON (8.9 ± 1.0). In general, our results show that PGR led to higher electron leakage in the form of free radical production and reactive oxygen species emission. No significant diet effects were found in protein abundance. The observed reduced respiratory control and increased ROS emission in PGR mice may increase risk for CVD in mice.

Use of individualized 3D-printed models of pancreatic cancer to improve surgeons' anatomic understanding and surgical planning.

OBJECTIVES: Three-dimensional (3D) printing has been increasingly used to create accurate patient-specific 3D-printed models from medical imaging data. We aimed to evaluate the utility of 3D-printed models in the localization and understanding of pancreatic cancer for surgeons before pancreatic surgery. METHODS: Between March and September 2021, we prospectively enrolled 10 patients with suspected pancreatic cancer who were scheduled for surgery. We created an individualized 3D-printed model from preoperative CT images. Six surgeons (three staff and three residents) evaluated the CT images before and after the presentation of the 3D-printed model using a 7-item questionnaire (understanding of anatomy and pancreatic cancer [Q1-4], preoperative planning [Q5], and education for trainees or patients [Q6-7]) on a 5-point scale. Survey scores on Q1-5 before and after the presentation of the 3D-printed model were compared. Q6-7 assessed the 3D-printed model's effects on education compared to CT. Subgroup analysis was performed between staff and residents. RESULTS: After the 3D-printed model presentation, survey scores improved in all five questions (before 3.90 vs. after 4.56, p < 0.001), with a mean improvement of 0.57‒0.93. Staff and resident scores improved after a 3D-printed model presentation (p < 0.05), except for Q4 in the resident group. The mean difference was higher among the staff than among the residents (staff: 0.50‒0.97 vs. residents: 0.27‒0.90). The scores of the 3D-printed model for education were high (trainees: 4.47 vs. patients: 4.60) compared to CT. CONCLUSION: The 3D-printed model of pancreatic cancer improved surgeons' understanding of individual patients' pancreatic cancer and surgical planning. CLINICAL RELEVANCE STATEMENT: The 3D-printed model of pancreatic cancer can be created using a preoperative CT image, which not only assists surgeons in surgical planning but also serves as a valuable educational resource for patients and students. KEY POINTS: • A personalized 3D-printed pancreatic cancer model provides more intuitive information than CT, allowing surgeons to better visualize the tumor's location and relationship to neighboring organs. • In particular, the survey score was higher among staff who performed the surgery than among residents. • Individual patient pancreatic cancer models have the potential to be used for personalized patient education as well as resident education.

Local Scheduling in KubeEdge-Based Edge Computing Environment.

KubeEdge is an open-source platform that orchestrates containerized Internet of Things (IoT) application services in IoT edge computing environments. Based on Kubernetes, it supports heterogeneous IoT device protocols on edge nodes and provides various functions necessary to build edge computing infrastructure, such as network management between cloud and edge nodes. However, the resulting cloud-based systems are subject to several limitations. In this study, we evaluated the performance of KubeEdge in terms of the computational resource distribution and delay between edge nodes. We found that forwarding traffic between edge nodes degrades the throughput of clusters and causes service delay in edge computing environments. Based on these results, we proposed a local scheduling scheme that handles user traffic locally at each edge node. The performance evaluation results revealed that local scheduling outperforms the existing load-balancing algorithm in the edge computing environment.

Camera Motion Agnostic Method for Estimating 3D Human Poses.

Although the performance of 3D human pose and shape estimation methods has improved considerably in recent years, existing approaches typically generate 3D poses defined in a camera or human-centered coordinate system. This makes it difficult to estimate a person's pure pose and motion in a world coordinate system for a video captured using a moving camera. To address this issue, this paper presents a camera motion agnostic approach for predicting 3D human pose and mesh defined in the world coordinate system. The core idea of the proposed approach is to estimate the difference between two adjacent global poses (i.e., global motion) that is invariant to selecting the coordinate system, instead of the global pose coupled to the camera motion. To this end, we propose a network based on bidirectional gated recurrent units (GRUs) that predicts the global motion sequence from the local pose sequence consisting of relative rotations of joints called global motion regressor (GMR). We use 3DPW and synthetic datasets, which are constructed in a moving-camera environment, for evaluation. We conduct extensive experiments and prove the effectiveness of the proposed method empirically.

Comparison of Super-Resolution US and Contrast Material-enhanced US in Detection of the Spoke Wheel Sign in Patients with Focal Nodular Hyperplasia.

Background Diagnosis of focal nodular hyperplasia (FNH) with US generally requires the use of contrast material. The effect of the super-resolution US technique on the diagnosis of FNH is unknown. Purpose To investigate the equivalence between super-resolution US and contrast material-enhanced US in the detection of spoke wheel sign in patients with FNH by comparing patterns of tumor vascularity. Materials and Methods This is a secondary analysis of a prospective trial (NCT02737865) that enrolled participants diagnosed with FNH between May 2016 and March 2019. These patients underwent super-resolution US and subsequent contrast-enhanced US with perfluorobutane microbubbles on the same day. The primary outcome was the confidence score of detecting spoke wheel sign in patients with FNH at US. Two radiologists used a four-point scale to score their confidence in the presence of the spoke wheel sign based on super-resolution US and contrast-enhanced US findings. Two one-sided tests were used to test the equivalence between super-resolution US and contrast-enhanced US in terms of the score for the confidence level of the spoke wheel sign. Interobserver agreement for both techniques between the two radiologists, using the recorded images, was analyzed by using an intraclass correlation coefficient. Results In 62 patients (mean age, 37 years; range, 20-69 years; 41 women) with FNH, the majority of patients showed a spoke wheel sign at super-resolution US and contrast-enhanced US (63% [39 of 62] and 71% [44 of 62], respectively; P = .36). There was no significant difference between the super-resolution US and contrast-enhanced US techniques regarding the confidence score for the spoke wheel sign (mean score, 1.8 vs 2.0; P = .03 for equivalence test). The intraclass correlation coefficients of super-resolution US and contrast-enhanced US regarding the presence of the spoke wheel sign were 0.82 (95% confidence interval: 0.73, 0.96) and 0.58 (95% confidence interval: 0.41, 0.73), respectively. Conclusion In comparison with contrast-enhanced US, super-resolution US provided a reliable rate of detection of the spoke wheel sign in patients with focal nodular hyperplasia. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Fetzer in this issue.

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).

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.

2-IPMA Ameliorates PM2.5-Induced Inflammation by Promoting Primary Ciliogenesis in RPE Cells.

Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction by increasing oxidative stress and inflammatory responses. Previously, we showed that PM disrupts the formation of primary cilia in retinal pigment epithelium (RPE) cells. In the present study, we identified 2-isopropylmalic acid (2-IPMA) as a novel inducer of primary ciliogenesis from a metabolite library screening. Both ciliated cells and primary cilium length were increased in 2-IPMA-treated RPE cells. Notably, 2-IPMA strongly promoted primary ciliogenesis and restored PM2.5-induced dysgenesis of primary cilia in RPE cells. Both excessive reactive oxygen species (ROS) generation and activation of a stress kinase, JNK, by PM2.5 were reduced by 2-IPMA. Moreover, 2-IPMA inhibited proinflammatory cytokine production, i.e., IL-6 and TNF-α, induced by PM2.5 in RPE cells. Taken together, our data suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in RPE cells.

Use of Gadoxetic Acid-enhanced Liver MRI and Mortality in More than 30 000 Patients with Hepatocellular Carcinoma: A Nationwide Analysis.

Background The impact on survival of gadoxetic acid-enhanced MRI in addition to multiphase contrast material-enhanced CT for initial staging in patients with hepatocellular carcinoma (HCC) is unknown. Purpose To compare all-cause mortality in patients with HCC who underwent CT only, CT plus non-gadoxetic acid-enhanced MRI, or CT plus gadoxetic acid-enhanced MRI as part of their initial diagnostic work-up. Materials and Methods The authors performed a nationwide retrospective cohort study of patients diagnosed with HCC in South Korea between January 2008 and December 2010. Follow-up extended through December 2014. The primary outcome was all-cause mortality. Cox proportional hazards regression model with adjustment of confounding factors was used to estimate hazard ratios (HRs) for all-cause mortality. Results Among 30 023 patients with HCC (mean age ± standard deviation, 58.5 years ± 10.7, 23 978 men), the proportions of patients in whom HCC was diagnosed using CT only, CT plus non-gadoxetic acid-enhanced MRI, and CT plus gadoxetic acid-enhanced MRI were 56.1%, 12.9%, and 31.0%, respectively. In adjusted analysis using CT only as the reference category, the HR for mortality for CT plus gadoxetic acid-enhanced MRI was 0.64 (95% confidence interval [CI]: 0.62, 0.67; P < .001), and the HR for CT plus non-gadoxetic acid-enhanced MRI was 0.71 (95% CI: 0.68, 0.75; P < .001). Use of CT plus gadoxetic acid-enhanced MRI was associated with lower mortality compared with CT plus non-gadoxetic acid-enhanced MRI (adjusted HR, 0.90; 95% CI: 0.85, 0.95; P < .001), but this survival advantage was restricted to patients with localized disease. Conclusion In patients with hepatocellular carcinoma, additional use of contrast-enhanced MRI was associated with lower mortality. Furthermore, CT plus gadoxetic acid-enhanced MRI was associated with better survival than CT plus non-gadoxetic acid-enhanced MRI but only in patients with localized disease. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kim in this issue.

Value of gadoxetic acid-enhanced MRI and diffusion-weighted imaging in the differentiation of hypervascular hyperplastic nodule from small (<3 cm) hypervascular hepatocellular carcinoma in patients with alcoholic liver cirrhosis: A retrospective case-control study.

BACKGROUND: Hypervascular hyperplastic nodules (HHNs) occasionally develop in patients with alcoholic liver cirrhosis (ALC) and show arterial enhancement, thus mimicking hepatocellular carcinoma (HCC). Importantly, HHN as a benign lesion should be distinguished from HCC. PURPOSE: To evaluate the value of gadoxetic acid-enhanced MRI (Gd-EOB-MRI) and diffusion-weighted imaging (DWI) in distinguishing HHN from small (<3 cm) hypervascular HCC (hHCC) in patients with ALC. STUDY TYPE: Retrospective case-control study. FIELD STRENGTH/SEQUENCE: 3.0T/in- and out-of-phase, T1 -weighted, T2 -weighted, diffusion-weighted, apparent diffusion coefficient, and dynamic gadoxetic acid-enhanced images. POPULATION: Among 560 patients with ALC who underwent Gd-EOB-MRI and DWI, 12 patients with 28 HHNs and 22 patients with 29 hHCCs smaller than 3 cm were included. ASSESSMENT: The following MRI features were evaluated by three independent radiologists: signal intensity (SI) on T1 -weighted, T2 -weighted, diffusion-weighted, and hepatobiliary phase (HBP) images; shape, homogeneity, and margin on HBP; diffusion restriction; intralesional fat; necrosis; hemorrhage; washout on portal venous phase (PVP) and/or transitional phase (TP); and capsular enhancement. Quantitative analysis was also conducted. STATISTICAL TESTS: Univariate and multivariate analyses were performed to determine the significant MRI findings, and their diagnostic performance for the prediction of HHN was analyzed. RESULTS: Lesion size of ≤16 mm (odds ratio [OR], 24.41; P = 0.007), low-to-iso SI on DWI (OR, 26.92; P = 0.007), and absence of washout on PVP and/or TP (OR, 31.84; P = 0.009) were significant independent factors for predicting HHN. When all three criteria were satisfied, the specificity was 100%. Compared with hHCCs, HHNs showed significantly smaller size (mean, 13.8 mm vs. 19.9 mm; P < 0.001) and higher mean SI value (994.0 vs. 669.5) and lesion-to-liver SI ratio (1.045 vs. 0.806) on HBP (P < 0.001, respectively). DATA CONCLUSION: Gd-EOB-MRI and DWI may be helpful in differentiating HHN from small hHCC in patients with ALC. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:70-80.

Single-Shot 3D Multi-Person Shape Reconstruction from a Single RGB Image.

Although the performance of the 3D human shape reconstruction method has improved considerably in recent years, most methods focus on a single person, reconstruct a root-relative 3D shape, and rely on ground-truth information about the absolute depth to convert the reconstruction result to the camera coordinate system. In this paper, we propose an end-to-end learning-based model for single-shot, 3D, multi-person shape reconstruction in the camera coordinate system from a single RGB image. Our network produces output tensors divided into grid cells to reconstruct the 3D shapes of multiple persons in a single-shot manner, where each grid cell contains information about the subject. Moreover, our network predicts the absolute position of the root joint while reconstructing the root-relative 3D shape, which enables reconstructing the 3D shapes of multiple persons in the camera coordinate system. The proposed network can be learned in an end-to-end manner and process images at about 37 fps to perform the 3D multi-person shape reconstruction task in real time.

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.

Apparent diffusion coefficient as a potential marker for tumour differentiation, staging and long-term clinical outcomes in gallbladder cancer.

OBJECTIVES: To evaluate the correlation between tumour differentiation or stage of gallbladder cancer (GBC) and the apparent diffusion coefficient (ADC), as well as to assess whether ADC value can predict long-term disease-free survival (DFS) after surgery. METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. Between March 2008 and June 2016, 79 patients who underwent magnetic resonance (MR) imaging with diffusion-weighted image and subsequent surgery for GBC were included in this study. Correlations between quantitative ADC values and tumour differentiation or stage based on the American Joint Committee on Cancer (AJCC) were assessed using Spearman's correlation analysis. Prognostic factors for DFS were identified with multivariate Cox regression analysis using imaging and clinical characteristics. RESULTS: All patients were classified as having well- (n = 18), moderately (n = 35) or poorly differentiated GBCs (n = 26). The ADC value of GBCs was significantly correlated with tumour differentiation and AJCC stage (p < 0.001 and p < 0.001, respectively). Sixty-nine patients were followed up for 2.0-92.4 months (median, 23.5 months). On multivariate analysis, the significant prognostic factor for DFS was not tumour differentiation or AJCC stage but a binary tumour ADC value (hazard ratio, 4.29; p = 0.009). DFS rates were significantly different according to the classification of tumour ADC value (cut-off value = 1.04 × 10-3 mm2/s; p = 0.004). CONCLUSION: The ADC value of GBCs was significantly correlated with tumour differentiation as well as AJCC stage. In addition, it predicted long-term outcomes after surgery in patients with GBC. KEY POINTS: • ADC values of GBC and tumour differentiation were negatively correlated. • Lower ADC values of GBC were significantly correlated with higher tumour stage. • Tumour ADC value could be useful for risk stratification of GBC patients.

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.

Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial.

OBJECTIVE: This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC. SUMMARY BACKGROUND DATA: Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC), no high-level evidence exists to support the role of such treatment. METHODS: This phase 2/3 multicenter randomized controlled trial was designed to enroll 110 patients with BRPC who were randomly assigned to gemcitabine-based neoadjuvant chemoradiation treatment (54 Gray external beam radiation) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea. The primary endpoint was the 2-year survival rate (2-YSR). Interim analysis was planned at the time of 50% case enrollment. RESULTS: After excluding the patients who withdrew consent (n = 8) from the 58 enrolled patients, 27 patients were allocated to neoadjuvant treatment and 23 to upfront surgery groups. The overall 2-YSR was 34.0% with a median survival of 16 months. In the intention-to-treat analysis, the 2-YSR and median survival were significantly better in the neoadjuvant chemoradiation than the upfront surgery group [40.7%, 21 months vs 26.1%, 12 months, hazard ratio 1.495 (95% confidence interval 0.66-3.36), P = 0.028]. R0 resection rate was also significantly higher in the neoadjuvant chemoradiation group than upfront surgery (n = 14, 51.8% vs n = 6, 26.1%, P = 0.004). The safety monitoring committee decided on early termination of the study on the basis of the statistical significance of neoadjuvant treatment efficacy. CONCLUSION: This is the first prospective randomized controlled trial on the oncological benefits of neoadjuvant treatment in BRPC. Compared to upfront surgery, neoadjuvant chemoradiation provides oncological benefits in patients with BRPC.

Pancreatic Ductal Adenocarcinoma: Rim Enhancement at MR Imaging Predicts Prognosis after Curative Resection.

Purpose To identify features at preoperative magnetic resonance (MR) imaging that could predict favorable prognosis after curative resection of pancreatic ductal adenocarcinoma (PDAC). Materials and Methods From January 2009 to December 2014, this retrospective study included 143 patients with surgically resected (ie, R0) PDAC who underwent preoperative MR imaging within 1 month before surgery. Clinical-pathologic and MR imaging findings for predicting disease-free survival (DFS) and overall survival (OS) were identified by using a Cox proportional hazards model. Important MR imaging features were compared with clinical-pathologic findings. Results Tumor size at histopathologic analysis was associated with both DFS and OS (hazard ratio per centimeter, 1.37; 95% confidence interval: 1.15, 1.63; P < .001 and hazard ratio, 1.44; 95% confidence interval: 1.20, 1.73; P < .001, respectively). Rim enhancement at dynamic contrast material-enhanced MR imaging was associated with significantly worse DFS and OS (hazard ratio, 1.72; 95% confidence interval: 1.05, 2.82; P = .030 and hazard ratio, 2.27; 95% confidence interval: 1.39, 3.69; P = .001, respectively). Diffusion-weighted imaging parameters, including diffusion restriction and apparent diffusion coefficient value, did not predict DFS or OS after resection of PDAC (all P > .05). Rim-enhancing lesions had more aggressive histologic tumor grades, less frequent remaining acini, and more frequent necrosis within the tumor compared with non-rim-enhancing pancreatic lesions (P = .002, P = .008, and P < .001, respectively). Conclusion Greater tumor size and rim enhancement were associated with lower DFS and OS rates after attempted curative resection of PDAC.

Imaging Features of Gadoxetic Acid-enhanced and Diffusion-weighted MR Imaging for Identifying Cytokeratin 19-positive Hepatocellular Carcinoma: A Retrospective Observational Study.

Purpose To determine the preoperative magnetic resonance (MR) imaging findings potentially most useful for predicting cytokeratin 19 (CK19)-positive hepatocellular carcinoma (HCC) and to evaluate the prognosis after curative resection in patients with a single HCC lesion positive for CK19 compared with patients with HCC who are negative for CK19. Materials and Methods The institutional review board approved this study and waived the requirement for informed consent. Two hundred four patients with CK19-negative HCC and 38 with CK19-positive HCC who underwent curative resection after gadoxetic acid-enhanced and diffusion-weighted MR imaging were retrospectively evaluated in a single institution. Two radiologists evaluated preoperative findings at MR imaging. Significant findings for differentiating the two groups were identified at univariate and multivariate analyses. By using receiver operating characteristic analysis, the optimal cut-off values for quantitative variables were determined. Recurrence-free survival rates after surgery were also compared between groups. Results At multivariate analysis, irregular tumor margin (P = .024), arterial rim enhancement (P < .001), lower tumor-to-liver signal intensity (SI) ratio on hepatobiliary phase (HBP) images (≤0.522; P = .01), and lower tumor-to-liver apparent diffusion coefficient (ADC) ratio (≤0.820; P < .001) were independent significant factors to predict CK19-positive HCC. When three of these four criteria were combined, 63.2% (24 of 38; 95% confidence interval: 46.0%, 78.2%) of CK19-positive HCCs were identified with a specificity of 90.7% (185 of 204; 95% confidence interval: 46.0%, 78.2%). When all four criteria were satisfied, specificity was 99.5% (203 of 204; 95% confidence interval: 97.3%, 100%). Recurrence-free survival rates were significantly lower in patients with CK19-positive HCCs compared with those with CK19-negative HCCs after curative resection (63.9% vs 90.0% at 1 year, 63.9% vs 79.9% at 2 years, and 54.8% vs 70.2% at 3 years, P = .001 by log-rank test). Conclusion At gadoxetic acid-enhanced and diffusion-weighted MR imaging, irregular margin, arterial phase rim enhancement, lower tumor-to-liver ADC ratio, and lower tumor-to-liver SI ratio at HBP imaging may be helpful to predict CK19-positive HCC with early recurrence (<2 years) after curative resection. © RSNA, 2017 Online supplemental material is available for this article.

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.