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Abstract Cultured meat is emerging as a new type of food that can provide animal protein in a sustainable way. Many previous studies employed various types of scaffolds to develop cultured meat with similar properties to slaughtered meat. However, important properties such as flavor were not discussed, even though they determine the quality of food. Flavor characteristics vary dramatically depending on the amount and types of amino acids and sugars that produce volatile compounds through the Maillard reaction upon cooking. In this study, a flavor-switchable scaffold is developed to release meaty flavor compounds only upon cooking temperature mimicking the Maillard reaction of slaughtered meat. By introducing a switchable flavor compound (SFC) into a gelatin-based hydrogel, we fabricate a functional scaffold that can enhance the aromatic properties of cultured meat. The temperature-responsive SFC stably remains in the scaffold during the cell culture period and can be released at the cooking temperature. Surprisingly, cultured meat fabricated with this flavor-switchable scaffold exhibits a flavor pattern similar to that of beef. This research suggests a strategy to develop cultured meat with enhanced sensorial characteristics by developing a functional scaffold which can mimic the natural cooking flavors of conventional meat.

Introduction: The Liver Imaging Reporting and Data System (LI-RADS) categorization has been proposed as a potential prognostic indicator for primary liver neoplasms in patients with liver cirrhosis or chronic hepatitis B. This multicenter study aimed to determine whether LI-RADS categorization can offer additional post-surgical prognostic value for intrahepatic cholangiocarcinoma (ICCA) when used in conjunction with the American Joint Committee on Cancer (AJCC) guidelines. Methods: Patients with high risk for hepatocellular carcinoma, surgically confirmed ICCAs, and available preoperative MRI were enrolled. LI-RADS categorization of ICCAs was performed using MRI features, and multivariate analyses were conducted incorporating LI-RADS category, AJCC staging, and clinicopathologic factors to evaluate their predictive value for postoperative recurrence-free survival (RFS) and overall survival (OS). In patients with early recurrence (

Abstract Background Sarcopenia or visceral adipose tissue has been reported to be related to pancreatic cancer prognosis. However, clinical relevance of the comprehensive analysis of body compositions and their longitudinal changes is lacking. This study analysed the association between body composition changes after chemotherapy and survival in patients with metastatic pancreatic cancer. Methods We retrospectively included 456 patients (mean age ± standard deviation, 61.2 ± 10.0 years; 272 males and 184 females) with metastatic pancreatic cancer who received palliative chemotherapy from May 2011 to December 2019. Using deep learning‐based, fully automated segmentation of contrast‐enhanced computed tomography (CT) at the time of diagnosis, cross‐sectional areas of muscle, subcutaneous adipose tissue and visceral adipose tissue were extracted from a single axial image of the portal venous phase at L3 level. Skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI) and mean skeletal muscle attenuation (MA) were calculated, and their effect on overall survival (OS) was analysed. Longitudinal changes in body composition and prognostic values were also analysed in a subgroup of patients with 2‐ and 6‐month follow‐up CT (n = 349). Results A total of 452 deaths occurred during follow‐up in the entire cohort. The survival rate was 49.3% (95% confidence interval [CI], 44.9–54.2) at 1 year and 3.7% (95% CI, 2.0–6.8) at 5 years. In multivariable analysis, higher MA (≥44.4 HU in males and ≥34.8 HU in females) at initial CT was significantly associated with better OS in both males and females (adjusted hazard ratio [HR], 0.706; 95% CI, 0.538–0.925; P = 0.012 for males, and HR, 0.656; 95% CI, 0.475–0.906; P = 0.010 for females), whereas higher SATI (≥42.8 cm2/m2 in males and ≥65.8 cm2/m2 in females) was significantly associated with better OS in female patients only (adjusted HR, 0.568; 95% CI, 0.388–0.830; P = 0.003). In longitudinal analysis, SMI, VATI and SATI significantly decreased between initial and 2‐month follow‐up CT, whereas mean MA significantly decreased between 2‐ and 6‐month follow‐up CT. In multivariable Cox regression analysis of longitudinal changes, which was stratified by disease control state, SATI change was significantly associated with OS in male patients (adjusted HR, 0.513; 95% CI, 0.354–0.745; P

Purpose: To unravel the mechanism regulating the phosphorylation of glycogen synthase kinase 3 (GSK3) and the correlation between the inhibitory phosphorylation of GSK3α and sperm motility in human. Materials and Methods: The phosphorylation and priming phosphorylated substrate-specific kinase activity of GSK3 were examined in human spermatozoa with various motility conditions. Results: In human spermatozoa, GSK3α/β was localized in the head, midpiece, and principal piece of tail and p-GSK3α(Ser21) was enriched in the midpiece. The ratio of p-GSK3α(Ser21)/GSK3α was positively coupled with normal sperm motility criteria of World Health Organization. In high-motility spermatozoa, p-GSK3α(Ser21) phosphotyrosine (p-Tyr) proteins but p-GSK3α(Tyr279) markedly increased together with decreased kinase activity of GSK3 after incubation in Ca2+ containing medium. In high-motility spermatozoa, p-GSK3α(Ser21) levels were negatively coupled with kinase activity of GSK3, and which was deregulated in low-motility spermatozoa. In high-motility spermatozoa, 6-bromo-indirubin-3’-oxime, an inhibitor of kinase activity of GSK3 increased p-GSK3α(Ser21) and p-Tyr proteins. p-GSK3α(Ser21) and p-Tyr protein levels were decreased by inhibition of PKA and Akt. Calyculin A, a protein phosphatase-1/2A inhibitor, markedly increased the p-GSK3α(Ser21) and p-Tyr proteins, and significantly increased the motility of low-motility human spermatozoa. Conclusions: Down regulation of kinase activity of GSK3α by inhibitory phosphorylation was positively coupled with human sperm motility, and which was regulated by Ca2+, PKA, Akt, and PP1. Small-molecule inhibitors of GSK3 and PP1 can be considered to potentiate human sperm motility.

Abstract Objectives To evaluate the inter-platform reproducibility of ultrasound-based fat fraction examination in nonalcoholic fatty liver disease (NAFLD). Methods Patients suspected of having NAFLD were prospectively enrolled from January 2023. Ultrasound-based fat fraction examinations were performed using two different platforms (ultrasound-derived fat fraction [UDFF] and quantitative ultrasound-derived estimated fat fraction [USFF]) on the same day. The correlation between UDFF and USFF was assessed using Pearson correlation coefficient. Intraclass correlation coefficient (ICC), Bland–Altman analysis with 95% limits of agreement (LOAs), and the coefficient of variation (CV) were used to assess inter-platform reproducibility. Results A total of 41 patients (21 men and 20 women; mean age, 53.9 ± 12.6 years) were analyzed. Moderate correlation was observed between UDFF and USFF (Pearson’s r = 0.748; 95% confidence interval [CI]: 0.572–0.858). On Bland–Altman analysis, the mean difference between UDFF and USFF values was 1.3% with 95% LOAs ranging from -8.0 to 10.6%. The ICC between UDFF and USFF was 0.842 (95% CI: 0.703–0.916), with a CV of 29.9%. Conclusion Substantial inter-platform variability was observed among different ultrasound-based fat fraction examinations. Therefore, it is not appropriate to use ultrasound-based fat fraction values obtained from different vendors interchangeably. Critical relevance statement Considering the substantial inter-platform variability in ultrasound-based fat fraction assessments, caution is imperative when interpreting and comparing fat fraction values obtained from different ultrasound platforms in clinical practice. Key points • Inter-platform reproducibility of ultrasound-based fat fraction examinations is important for its clinical application. • Significant variability across different ultrasound-based fat fraction examinations was observed. • Using ultrasound-based fat fraction values from different vendors interchangeably is not advisable. Graphical Abstract

Abstract Background Percutaneous radiofrequency ablation (RFA) is pivotal for treating small malignant liver tumors, but tumors often remain inconspicuous on B-mode ultrasound (US). This study evaluates the potential of CEUS-CT/MRI fusion imaging (FI) to improve tumor visibility and the associated RFA outcomes for small (≤ 3 cm) malignant liver tumors that were inconspicuous on US. Methods Between January 2019 and April 2021, a prospective study enrolled 248 patients with liver malignancies (≤ 3 cm) that were poorly visible on B-mode US. Tumor visibility and ablation feasibility were assessed using B-mode US, US-CT/MRI FI, and CEUS-CT/MRI FI, and graded on a 4-point scale. CEUS was employed post-registration of US and CT/MRI images, utilizing either SonoVue or Sonazoid. Comparisons between US-based and CEUS-based fusion visibility and feasibility scores were undertaken using the Friedman test. Moreover, rates of technical success, technique efficacy, local tumor progression (LTP), and major complications were assessed. Results The cohort included 223 hepatocellular carcinomas (HCCs) (89.9%) and 23 metastases (9.3%), with an average tumor size of 1.6 cm. CEUS-CT/MRI FI demonstrated a significant advantage in tumor visibility (3.4 ± 0.7 vs. 1.9 ± 0.6, P

Abstract Research on cultured meat has primarily focused on the mass proliferation or differentiation of muscle cells; thus, the food characteristics of cultured meat remain relatively underexplored. As the quality of meat is determined by its organoleptic properties, cultured meat with similar sensory characteristics to animal-derived meat is highly desirable. In this study, we control the organoleptic and nutritional properties of cultured meat by tailoring the 2D differentiation of primary bovine myoblasts and primary bovine adipose-derived mesenchymal stem cells on gelatin/alginate scaffolds with varying stiffness. We assess the effect of muscle and adipose differentiation quality on the sensory properties of cultured meat. Thereafter, we fabricate cultured meat with similar sensory profiles to that of conventional beef by assembling the muscle and adipose constructs composed of highly differentiated cells. We introduce a strategy to produce cultured meat with enriched food characteristics by regulating cell differentiation with scaffold engineering.

Abstract Objectives To assess the resectability of pancreatic ductal adenocarcinoma (PDAC), the evaluation of tumor vascular contact holds paramount significance. This study aimed to compare the image quality and diagnostic performance of high-resolution (HR) pancreas computed tomography (CT) using an 80 kVp tube voltage and a thin slice (1 mm) for assessing PDAC resectability, in comparison with the standard protocol CT using 120 kVp. Methods This research constitutes a secondary analysis originating from a multicenter prospective study. All participants underwent both the standard protocol pancreas CT using 120 kVp with 3 mm slice thickness (ST) and HR-CT utilizing an 80 kVp tube voltage and 1 mm ST. The contrast-to-noise ratio (CNR) between parenchyma and tumor, along with the degree of enhancement of the abdominal aorta and main portal vein (MPV), were measured and subsequently compared. Additionally, the likelihood of margin-negative resection (R0) was evaluated using a five-point scale. The diagnostic performance of both CT protocols in predicting R0 resection was assessed through the area under the receiver operating characteristic curve (AUC). Results A total of 69 patients (37 males and 32 females; median age, 66.5 years) were included in the study. The median CNR of PDAC was 10.4 in HR-CT, which was significantly higher than the 7.1 in the standard CT (P=0.006). Furthermore, HR-CT demonstrated notably higher median attenuation values for both the abdominal aorta (579.5 HU vs. 327.2 HU; P=0.002) and the MPV (263.0 HU vs. 175.6 HU; P=0.004) in comparison with standard CT. Following surgery, R0 resection was achieved in 51 patients. The pooled AUC for HR-CT in predicting R0 resection was 0.727, slightly exceeding the 0.699 of standard CT, albeit lacking a significant statistical distinction (P=0.128). Conclusion While HR pancreas CT using 80 kVp offered a notably greater degree of contrast enhancement in vessels and a higher CNR for PDAC compared to standard CT, its diagnostic performance in predicting R0 resection remained statistically comparable.

Background and aimsWith the rapid growth of artificial intelligence (AI) applications in various fields, understanding its impact on liver cancer research is paramount. This scientometrics project aims to investigate publication trends and topics in AI-related publications in liver cancer.Materials and MethodsWe employed a search strategy to identify AI-related publications in liver cancer using Scopus database. We analyzed the number of publications, author affiliations, and journals that publish AI-related publications in liver cancer. Finally, the publications were grouped based on intended application.ResultsWe identified 3950 eligible publications (2695 articles, 366 reviews, and 889 other document types) from 1968 to August 3, 2023. There was a 12.7-fold increase in AI-related publications from 2013 to 2022. By comparison, the number of total publications on liver cancer increased by 1.7-fold. Our analysis revealed a significant shift in trends of AI-related publications on liver cancer in 2019. We also found a statistically significant consistent increase in numbers of AI-related publications over time (tau = 0.756, p < 0.0001). Eight (53%) of the top 15 journals with the most publications were radiology journals. The largest number of publications were from China (n=1156), the US (n=719), and Germany (n=236). The three most common publication categories were “medical image analysis for diagnosis” (37%), “diagnostic or prognostic biomarkers modeling & bioinformatics” (19%), and “genomic or molecular analysis” (18%).ConclusionOur study reveals increasing interest in AI for liver cancer research, evidenced by a 12.7-fold growth in related publications over the past decade. A common application of AI is in medical imaging analysis for various purposes. China, the US, and Germany are leading contributors.

Abstract Background Although efforts have been made to reduce the dose of Contrast Medium (CM) to improve patient safety, there are ongoing concerns regarding its potential effects on image quality and diagnostic performance. Moreover, research is lacking to establish a lower limit for safe and effective CM dose reduction. To determine whether the image quality of contrast-enhanced liver computed tomography (CT) using a reduced amount of iodinated CM was similar to that of standard liver CT. Methods We enrolled participants at risk for hepatocellular carcinoma with decreased estimated glomerular filtration rates ( 0.017). Conclusions The reduction in image contrast and overall image quality caused by decreased CM can be restored using either low monoenergetic imaging or DL-based iodine-boosting reconstruction. Trial registration clinicaltrials.gov, NCT04024514, Registered July 18, 2019, prospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT04024514 .

Abstract Background To predict whether the left pulmonary artery (LPA) to the main pulmonary artery (MPA) ratio measured by echocardiography in left congenital diaphragmatic hernia (CDH) was related to death or need for extracorporeal membrane oxygenation (ECMO). Methods This retrospective study analyzed neonates with left CDH born between 2018 and 2022 in a single tertiary medical institution. Echocardiography was performed immediately after birth. The diameter of the LPA was measured at the bifurcation, and the diameter of the MPA was measured at the maximal dimension during the systolic phase. The Nakata index, McGoon ratio, and ejection fraction (EF) were analyzed and compared with the LPA: MPA ratio as predictive values. Results Seventy-two neonates with left CDH were included, 19 (26.4%) died or needed ECMO, and 53 (73.6%) survived without ECMO. The lower observed/expected lung-to-head ratio, lower EF, lower LPA: MPA ratio, lower RPA: MPA ratio, lower Nakata index, and lower McGoon ratio were associated with death or need for ECMO. By multivariate analysis, lower LPA: MPA ratio, RPA: MPA ratio, and Nakata index were independent postnatal risk factors for death or need for ECMO. Among the measurements, the LPA: MPA ratio had the highest area under the curve (0.957) with a sensitivity of 84.2% and specificity of 96.3% at a cut-off value of 31.2%. Conclusion In patients with left CDH, the LPA: MPA ratio measured by echocardiography could be used as an independent postnatal predictor of death or need for ECMO.

Contrast-enhanced ultrasonography (CEUS) is a noninvasive imaging modality used to diagnose hepatocellular carcinoma (HCC) based on specific imaging features, without the need for pathologic confirmation. Two types of ultrasound contrast agents are commercially available: pure intravascular agents (such as SonoVue) and Kupffer agents (such as Sonazoid). Major guidelines recognize CEUS as a reliable imaging method for HCC diagnosis, although they differ depending on the contrast agents used. The Korean Liver Cancer Association–National Cancer Center guideline includes CEUS with either SonoVue or Sonazoid as a second-line diagnostic technique. However, Sonazoid-enhanced ultrasound is associated with several unresolved issues. This review provides a comparative overview of these contrast agents regarding pharmacokinetic features, examination protocols, diagnostic criteria for HCC, and potential applications in the HCC diagnostic algorithm.

Abstract This study developed and validated multivariable quantitative ultrasound (QUS) model for diagnosing hepatic steatosis. Retrospective secondary analysis of prospectively collected QUS data was performed. Participants underwent QUS examinations and magnetic resonance imaging proton density fat fraction (MRI-PDFF; reference standard). A multivariable regression model for estimating hepatic fat fraction was determined using two QUS parameters from one tertiary hospital (development set). Correlation between QUS-derived estimated fat fraction(USFF) and MRI-PDFF and diagnostic performance of USFF for hepatic steatosis (MRI-PDFF ≥ 5%) were assessed, and validated in an independent data set from the other health screening center(validation set). Development set included 173 participants with suspected NAFLD with 126 (72.8%) having hepatic steatosis; and validation set included 452 health screening participants with 237 (52.4%) having hepatic steatosis. USFF was correlated with MRI-PDFF (Pearson r = 0.799 and 0.824; development and validation set). The model demonstrated high diagnostic performance, with areas under the receiver operating characteristic curves of 0.943 and 0.924 for development and validation set, respectively. Using cutoff of 6.0% from development set, USFF showed sensitivity, specificity, positive predictive value, and negative predictive value of 87.8%, 78.6%, 81.9%, and 85.4% for diagnosing hepatic steatosis in validation set. In conclusion, multivariable QUS parameters-derived estimated fat fraction showed high diagnostic performance for detecting hepatic steatosis.

Abstract Background Anatomical ablation, defined as thermal ablation of tumor-bearing small portal territories, may provide excellent local tumor control in peripherally-located small hepatocellular carcinomas (HCC), which has been a major concern with percutaneous ablation alone. Purpose To evaluate the technical feasibility and therapeutic outcomes of anatomical ablation using multiple radiofrequency (RF) applicators for the ablation of tumor-bearing small portal territories of peripherally-located small (≤ 4 cm) HCCs. Materials and methods Patients with peripherally-located single HCCs (≤ 4 cm) to be treated with anatomical ablation using multiple RF applicators between January 2020 and March 2022 were enrolled in this prospective study. Anatomical ablation was performed for the index tumor under real-time US-CT/MR fusion imaging guidance, with one or two clustered electrode needles placed across the tumor-bearing portal vein branches. Technical success and complications of anatomical ablations were assessed. Cumulative incidence of local tumor progression (LTP) and recurrence-free survival were estimated using the Kaplan–Meier method. Results Fifty-five HCCs (mean size, 1.77 ± 0.59 cm) in 55 participants (mean age, 66.4 ± 7.7 years; 39 men, 16 women) were treated with anatomical ablation; 98.2% (54/55) technical success was achieved. No major complications were noted. Among the 55 participants, LTP occurred in only one patient who had experienced technical failure of anatomical ablation. Estimated 1- and 2-year cumulative incidences of LTP were 0% and 3.7%, respectively. Five patients developed intrahepatic remote recurrence during the median follow-up period of 19.2 months (range, 3.7–28.8 months); therefore, estimated 1- and 2-year recurrence-free survival was 91.7% and 85.0%, respectively. Conclusion Anatomical ablation using multiple RF applicators provided the excellent results of local tumor control in patients with peripherally-located small (≤ 4 cm) HCCs. Trial registration clinicaltrial.gov identifier: NCT05397860.

Abstract Background Loss of muscle mass is the most common complication of end-stage liver disease and negatively affects outcomes for liver transplantation (LT) recipients. We aimed to determine the prognostic value of a fully automated three-dimensional (3D) muscle volume estimation using deep learning algorithms on abdominal CT in patients who underwent liver transplantation (LT). Methods This retrospective study included 107 patients who underwent LT from 2014 to 2015. Serial CT scans, including pre-LT and 1- and 2-year follow-ups were performed. From the CT scans, deep learning-based automated body composition segmentation software was used to calculate muscle volumes in 3D. Sarcopenia was calculated by dividing average skeletal muscle area by height squared. Newly developed-(ND) sarcopenia was defined as the onset of sarcopenia 1 or 2 years after LT in patients without a history of sarcopenia before LT. Patients’ clinical characteristics, including post-transplant diabetes mellitus (PTDM) and Model for end-stage liver disease score, were compared according to the presence or absence of sarcopenia after LT. A subgroup analysis was performed in the post-LT sarcopenic group. The Kaplan–Meier method was used for overall survival (OS). Results Patients with ND-sarcopenia had poorer OS than those who did not (P = 0.04, hazard ratio [HR], 3.34; 95% confidence interval [CI] 1.05 – 10.7). In the subgroup analysis for post-LT sarcopenia (n = 94), 34 patients (36.2%) had ND-sarcopenia. Patients with ND-sarcopenia had significantly worse OS (P = 0.002, HR 7.12; 95% CI 2.00 – 25.32) and higher PTDM occurrence rates (P = 0.02, HR 4.93; 95% CI 1.18 – 20.54) than those with sarcopenia prior to LT. Conclusion ND-sarcopenia determined by muscle volume on abdominal CT can predict poor survival outcomes and the occurrence of PTDM for LT recipients.

AbstractBackground The novel separable clustered electrode system with two adjustable active tips (ICAEs) and a fine multipurpose needle (MPN) for in situ temperature monitoring and adjuvant agent injection was developed and validated in an animal study. The purpose of this study was to evaluate the technical efficacy and complication of the novel electrode system for patients who have small HCC.Methods In this prospective, single-center clinical trial, ten participants with 14 small (≤ 2 cm, BCLC 0-A) HCCs referred for RFA were enrolled. A novel electrode system consisting of two ICAEs and one MPN with a thermometer and side holes was used for RFA. The RF energy was delivered using a multichannel RF system combining bipolar and switching monopolar modes. Technical success, efficacy, and complications were evaluated on immediate and one-month follow-up CT.Results Technical success was achieved in 92.9% (13/14) of tumors. One participant withdrew consent after RFA, and technical efficacy was achieved in 91.7% (11/12) of tumors. None showed thermal injury to nontarget organs. All patients were discharged the day after RFA without major complications. The active electrode lengths were adjusted in 60% (6/10) of patients during the procedure to tailor the ablation zone (83.3%, n = 5) or treat two tumors with different sizes (16.7%, n = 1). MPN was capable of continuous temperature monitoring during all ablations (100%, 14/14).Conclusions RFA using a novel electrode system showed acceptable technical efficacy and safety in patients with small HCCs. Further comparative studies are needed for the investigation of the system’s potential benefits compared to conventional electrodes.

AbstractPurpose: To investigate the feasibility rate and the mid-term outcomes of fusion imaging-guided radiofrequency ablation (RFA) with artificial ascites or pleural effusion of hepatocellular carcinomas (HCCs) based on tumor locations.Materials and Methods: In this single-center retrospective study, 456 patients with single HCCs ≤4 cm were referred for RFA from April 2019 to April 2020. The tumor locations were classified into a conventional location (CL) and difficult location (DL, close to the diaphragm/heart/major vessels/bile ducts/gastrointestinal tract/kidneys). This study assessed the feasibility rate of CT/MRI-US fusion system-guided RFA with artificial ascites or pleural effusion and the therapeutic outcomes including technical success, technique efficacy, and local tumor progression (LTP) according to tumor location. Cumulative LTP rates were estimated using the Kaplan–Meier method.Results: 235 of 456 (51.5%) patients had HCCs in DL. Ablation was feasible in 431 of 456 (94.5%) patients. The feasibility rate was significantly lower in DL group than in CL group (89.8% [211/235] vs. 99.5% [220/221], p 0.05). The estimated 1-, 2-, and 3-year cumulative LTP rates in DL group were 1.0%, 2.5%, and 2.5%, respectively, and were not significantly different from the 2.3%, 3.9%, and 3.9% observed in CL group (p = 0.456).Conclusion: Fusion imaging-guided RFA with artificial ascites or pleural effusion could decrease technically infeasible cases and provide comparable LTP rates for HCCs in DL to HCCs in CL.

Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent because of its tumor selectivity and its ability to induce apoptosis in cancer cells while sparing most normal cells. We evaluated whether docetaxel enhances TRAIL-mediated apoptosis in prostate cancer (PCa) cells and its mechanism. Materials and Methods: LNCap-LN3, PC3, and DU 145 PCa cell lines were used to investigate the effects of TRAIL with docetaxel treatment (dosages, 1, 3, 5, and 10 nmol). To evaluate the mechanism, death receptor 4 (DR4), DR5, enhancer of zeste homolog 2 (EZH2) and E2F1 levels were assessed in PCa cells. Results: Hormone-sensitive LNCap-LN3 showed apoptosis in proportion to the concentration of docetaxel. Castration-resistant PC3 and DU 145 showed no change irrespective of the docetaxel concentration. However, combinations of docetaxel (2 nM) and TRAIL (100 ng/mL) had a significant effect on apoptosis of DU 145 cells. In DU 145 cells, docetaxel reduced EZH2 and elevated expression of DR4. The decrease of EZH2 by docetaxel was correlated with the E2F1 level, which was considered as the promoter of EZH2. DZNep reduced EZH2 and elevated DR4 in all PCa cells. Additionally, DZNep-enhanced TRAIL mediated reduction of PCa cell viability. Conclusions: Docetaxel and the EZH2 inhibitor reduced EZH2 and elevated expression of DR4 in all PCa cell lines. Docetaxel-enhanced TRAIL mediated apoptosis in PCa via elevation of DR4 through epigenetic regulation by EZH2. To improve the efficacy of TRAIL for PCa treatment, adding docetaxel or EZH2 inhibitors to TRAIL may be promising.

Purpose Extremely low birth weight (ELBW) infants exhibit immature thermoregulation and are easily exposed to hypothermia. We investigated the association between hypothermia on admission with short- and long-term outcomes. Methods Medical records of ELBW infants admitted to the neonatal intensive care unit of a tertiary medical center between June 2012 and February 2017 were retrospectively analyzed. Upon admission, the axillary body temperature was measured. Moderate hypothermia was defined as admission temperature below 36 ℃. Results A total of 208 infants with gestational age of 26.4±2.3 weeks and birth weight of 746.7±154.9 g were included. Admission temperature ranged from 33.5 to 36.8 ℃ (median 36.1 ℃). Univariate analyses of maternal and infant characteristics were performed for moderately hypothermic and control (normothermic to mildly hypothermic) infants. Lower gestational age, lower birth weight, and vaginal delivery correlated with moderate hypothermia. Logistic regression analyses adjusted for confounders revealed that the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) was associated with moderate hypothermia in ELBW infants. Moreover, abnormal mental developmental index scores on the Bayley Scales of Infant Development II at a corrected age of 18 to 24 months were associated with moderate hypothermia, but not with the psychomotor developmental index, incidence of blindness, deafness, or cerebral palsy. Conclusion Moderate hypothermia at admission is not only correlated with short-term neonatal morbidities such as hsPDA, but may also be associated with long-term neurodevelopmental impairment in ELBW infants. Future large-scale studies are required to clarify the long-term consequences of hypothermia upon admission.

Purpose We investigated the effects of early postnatal administration of erythropoietin (EPO) on neurodevelopmental outcomes and morbidities in preterm infants with severe grades of intraventricular hemorrhage (IVH). Methods We retrospectively reviewed the medical records of preterm infants of gestational age 23+0 weeks to 31+6 weeks, who were diagnosed with severe grades of IVH and received EPO over at least 2 weeks. We compared clinical characteristics, major complications, and neurodevelopmental impairment between the two groups. The primary outcome was severe neurodevelopmental impairment at 18 to 26 months of corrected age. Severe neurodevelopmental impairment was defined as a mental developmental index or psychomotor developmental index of

Abstract Background CT prediction of resectability and prognosis following neoadjuvant treatment (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC) remains challenging. This study aims to determine whether addition of 18F-fluorodeoxyglucose (FDG) postiron emission tomography (PET)/MRI and carbohydrate antigen (CA) 19–9 to contrast-enhanced CT (CECT) can improve accuracy of predicting resectability compared to CECT alone and predict prognosis in PDAC patients after NAT. Methods In this retrospective study, 120 PDAC patients (65 women; mean age, 66.7 years [standard deviation, 8.4]) underwent CECT, PET/MRI, and CA 19–9 examinations after NAT between January 2013 and June 2021. Three board-certified radiologists independently rated the overall resectability on a 5-point scale (score 5, definitely resectable) in three sessions (session 1, CECT; 2, CECT plus PET/MRI─no FDG avidity and no diffusion restriction at tumor-vessel contact indicated modification of CECT scores to ≥ 3; 3, CECT plus PET plus CA 19–9─no FDG avidity at tumor-vessel contact and normalized CA 19–9 indicated modification of CECT scores to ≥ 3). Jackknife free-response receiver operating characteristic method and generalized estimating equations were used to compare pooled area under the curve (AUC), sensitivity, and specificity of three sessions. Predictors for recurrence-free survival (RFS) were assessed using Cox regression analyses. Results Each session showed different pooled AUC (session 1 vs. 2 vs. 3, 0.853 vs. 0.873 vs. 0.874, p = 0.026), sensitivity (66.2% [137/207] vs. 86.0% [178/207] vs. 84.5% [175/207], p

The present study aims to explore the probable anti-adipogenesis effect of Dictyopteris divaricata (D. divaricata) in 3T3-L1 preadipocytes by regulating heme oxygenase-1 (HO-1). The extract of D. divaricata retarded lipid accretion and decreased triglyceride (TG) content in 3T3-L1 adipocytes but increased free glycerol levels. Treatment with the extract inhibited lipogenesis by inhibiting protein expressions of fatty acid synthase (FAS) and lipoprotein lipase (LPL), whereas lipolysis increased by activating phosphorylation of hormone-sensitive lipase (p-HSL) and AMP-activated protein kinase (p-AMPK). The extract inhibited adipocyte differentiation of 3T3-L1 preadipocytes through down-regulating adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1). This is attributed to the triggering of Wnt/β-catenin signaling. In addition, this study found that treatment with the extract activated HO-1 expression. Pharmacological approaches revealed that treatment with Zinc Protoporphyrin (ZnPP), an HO-1 inhibitor, resulted in an increase in lipid accumulation and a decrease in free glycerol levels. Finally, three adipogenic transcription factors, such as PPARγ, C/EBPα, and SREBP1, restored their expression in the presence of ZnPP. Analysis of chemical constituents revealed that the extract of D. divaricata is rich in 1,4-benzenediol, 7-tetradecenal, fucosterol, and n-hexadecanoic acid, which are known to have multiple pharmacological properties.

Purpose This study compared two different two-dimensional shear wave elastography techniques—plane wave imaging (PWI) and multi-beam (MB) imaging—from the same vendor to evaluate liver fibrosis. Methods In this prospective study, 42 patients with chronic liver disease who had recently undergone magnetic resonance elastography (

The control of intestinal α-amylase and α-glucosidase is an effective therapeutic strategy for prevention of post-prandial hyperglycemia associated with diabetes mellitus. The objective of this study was to evaluate the anti-diabetes activities of Korean edible seaweed against α-amylase and α-glucosidase, two carbolytic enzymes involved in serum glucose regulation. Of the 41 species initially screened, Cladophora wrightiana var. minor, Eisenia bicyclis, Ecklonia cava, Ishige foliacea, and Ishige okamurae exhibited the strongest inhibitory activities from brown seaweeds. Asparagopsis taxiformis showed the strongest inhibitory effects from red seaweeds. The results of this study suggest that the crude brown seaweed extracts (C. wrightiana var. minor, E. bicyclis, E. cava, I. foliacea, and I. okamurae) and crude red seaweed extracts (A. taxiformis) may have beneficial effects suppressing the rise in postprandial hyperglycemia through the inhibition of α-amylase and α-glucosidase.

Intermuscular fat is essential for enhancing the flavor and texture of cultured meat. Mesenchymal stem cells derived from intermuscular adipose tissues are a source of intermuscular fat. Therefore, as a step towards developing a platform to derive intermuscular fat from mesenchymal stem cells (MSCs) for insertion between myofibrils in cultured beef, an advanced protocol of intermuscular adipose tissue dissociation effective to the isolation of MSCs from intermuscular adipose tissues was developed in cattle. To accomplish this, physical steps were added to the enzymatic dissociation of intermuscular adipose tissues, and the MSCs were established from primary cells dissociated with physical step-free and step-added enzymatic dissociation protocols. The application of a physical step (intensive shaking up) at 5 minutes intervals during enzymatic dissociation resulted in the greatest number of primary cells derived from intermuscular adipose tissues, showed effective formation of colony forming units-fibroblasts (CFU-Fs) from the retrieved primary cells, and generated MSCs with no increase in doubling time. Thus, this protocol will contribute to the stable supply of good quality adipose-derived mesenchymal stem cells (ADMSCs) as a fat source for the production of marbled cultured beef.

Research on the potential biological activity of red alga Symphyocladia spp. has been limited to Symphyocladia latiuscula, which is widely used as a food ingredient in Korea. Here, we examined the biological activity of another species, Symphyocladia linearis, which is found in Korea and was reported as a new species in 2013. The aim of this study was to evaluate the antioxidant, anti-inflammatory, and antibacterial properties of a 70% ethanol extract of S. linearis. Antioxidant activity, which was evaluated using radical scavenging assays, revealed half maximal inhibitory concentration values for 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) of 34.57 and 11.70 μg/mL algal extract, respectively. Anti-inflammatory activity of the S. linearis ethanolic extract was evaluated using RAW 264.7 cells by measuring the inhibition of lipopolysaccharide-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. The potential cytotoxicity of NO and PGE2 was first examined, confirming no toxicity at concentrations ranging from 10-100 μg/mL. NO production was inhibited 61.1% and 78.0% at 50 and 100 μg/mL S. linearis extract, respectively; and PGE2 production was inhibited 69.1%, 83.2%, and 94.8% at 25, 50, and 100 μg/mL S. linearis extract, respectively. Thus, the S. linearis extract showed very strong efficacy against PGE2 production. The cellular production of reactive oxygen species, measured using 2′,7′-dichlorofluorescin diacetate fluorescence, was inhibited 48.8% by the addition of 100 μg/mL S. linearis extract. Antibacterial activity was evaluated using the disc diffusion method and minimum inhibitory concentration (MIC). S. linearis was effective only against gram-positive bacteria, exhibiting antibacterial activity against Staphylococcus aureus with a MIC of 256 μg/mL extract and against Bacillus cereus with a MIC of 1,024 μg/mL extract. Based on these results, we infer that a 70% ethanolic extract of S. linearis possesses strong anti-inflammatory properties, and therefore has the potential to be used in the prevention and treatment of inflammatory and immune diseases.

Sargassum horneri is a seaweed species with diverse bioactivities. However, its antifibrotic effects during nasal polyp (NP) formation are not clearly understood. Therefore, we investigated the inhibitory effect of S. horneri on fibrosis progression in NP-derived fibroblasts (NPDFs) and NP tissues ex vivo. NPDFs were stimulated with TGF-β1 in the presence or absence of S. horneri ethanol extract (SHE). The extracellular matrix (ECM) protein production levels, myofibroblast differentiation (α-smooth muscle actin, α-SMA), and phosphorylation of Smad 2/3 and -ERK in TGF-β1-stimulated NPDFs were investigated using western blotting. Further, the contractile activity of SHE was assessed by performing a collagen gel contraction assay. The expression levels of collagen-1, fibronectin, and α-SMA were investigated in NP organ cultures treated with SHE. TGF-β1 stimulated ECM protein expression, myofibroblast differentiation, and collagen contractile activity while these were attenuated by pretreatment with SHE. We also found antifibrotic effect of SHE on ex vivo NP tissues. The antifibrotic effects of SHE were modulated through the attenuation of Smad 2/3 and ERK signaling pathways in TGF-β1-stimulated NPDFs. In conclusion, SHE inhibited ECM protein accumulation and myofibroblast differentiation during NP remodeling. Thus, SHE may be helpful as a treatment for NP recurrence after endoscopic sinus surgery.

Abstract Aims/Introduction We investigated the classification of diabetic peripheral neuropathy (DPN) patients by subjective symptoms, and identification of the relationship between the patterns and intensities of symptoms and the clustered groups of DPN patients. Materials and Methods This multicenter study analyzed epidemiological data and sensory symptoms of 649 patients with DPN. Cluster analysis was carried out to identify subgroups of patients with characteristic symptom profiles. Factor analysis was carried out to investigate the symptom patterns of the clustered groups of DPN patients. Results Three clusters of patients with DPN were identified: severe symptoms with decreased quality of life (cluster 1, n = 119, 18.3%), predominantly insensate symptoms with relatively good quality of life (cluster 2, n = 318, 49.0%), and moderate pain intensity and decreased quality of life (cluster 3, n = 204, 31.4%). The frequency of symptoms on each item of the Michigan Neuropathy Screening Instrument questionnaire showed a similar distribution according to pain intensities along with the three clusters. Conclusions Our study supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach. Based on a multicenter study, we identified three clusters of patients with DPN. Our research supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach.

Hepatocellular carcinoma (HCC) is a unique cancer entity that can be noninvasively diagnosed using imaging modalities without pathologic confirmation. In 2018, several major guidelines for HCC were updated to include hepatobiliary contrast agent magnetic resonance imaging (HBA-MRI) and contrast-enhanced ultrasound (CEUS) as major imaging modalities for HCC diagnosis. HBA-MRI enables the achievement of high sensitivity in HCC detection using the hepatobiliary phase (HBP). CEUS is another imaging modality with real-time imaging capability, and it is reported to be useful as a second-line modality to increase sensitivity without losing specificity for HCC diagnosis. However, until now, there is an unsolved discrepancy among guidelines on whether to accept “HBP hypointensity” as a definite diagnostic criterion for HCC or include CEUS in the diagnostic algorithm for HCC diagnosis. Furthermore, there is variability in terminology and inconsistencies in the definition of imaging findings among guidelines; therefore, there is an unmet need for the development of a standardized lexicon. In this article, we review the performance and limitations of HBA-MRI and CEUS after guideline updates in 2018 and briefly introduce some future aspects of imaging-based HCC diagnosis.

Purpose This study aimed to assess the inter-platform reproducibility of ultrasound attenuation examination in patients with nonalcoholic fatty liver disease (NAFLD). Methods Between March 2021 and April 2021, patients with clinically suspected or known NAFLD were prospectively enrolled; each patient underwent ultrasound attenuation examinations with three different platforms (Attenuation Imaging [ATI], Canon Medical System; Tissue Attenuation Imaging [TAI], Samsung Medison; and Ultrasound-Guided Attenuation Parameter [UGAP], GE Healthcare) on the same day. The mean attenuation coefficient (AC) values of the three platforms were compared using repeated-measures analysis of variance with the Bonferroni correction. To evaluate inter-platform reproducibility, the AC values obtained for each platform were compared using Bland-Altman analysis with the calculation of 95% limits of agreement (LOA), intraclass correlation coefficients (ICCs), and coefficients of variation (CVs). Results Forty-six patients (23 men; mean age±standard deviation, 52.3±12.4 years) were enrolled. The mean AC values showed significant differences among the three platforms (0.75±0.12, 0.80±0.11, and 0.74±0.09 dB/cm/MHz for ATI, TAI, and UGAP, respectively; P

Introduction: Small-duct (SD) and large-duct (LD) subtypes of cholangiocarcinoma have been investigated for their prognostic factors. This study aimed to evaluate the diagnostic value of liver magnetic resonance imaging (MRI) in differentiating SD and LD types of intrahepatic cholangiocarcinoma (iCCA) and its prognostic value in predicting survival outcomes. Methods: One hundred forty patients with surgically confirmed iCCAs (93 SD type and 47 LD type) who had available preoperative gadoxetic acid-enhanced liver MR images were retrospectively included. MRI features suggestive of the LD type over the SD type were analyzed using multivariate logistic analyses. Postoperative recurrence-free survival (RFS) and overall survival (OS) for 107 patients with available survival data were compared according to MRI features. Results: MRI features suggestive of the LD type included infiltrative contour (odds ratio [OR] 14.2, 95% confidence interval [CI]: 2.5–81.7, p = 0.003), diffuse biliary dilatation (OR 9.7, 95% CI: 1.2–76.9, p = 0.032), no arterial phase hyperenhancement (OR 17.8, 95% CI: 2.7–118.6, p = 0.003), and vascular invasion (OR 4.5, 95% CI: 1.3–15.4, p = 0.018). When two or more features were combined, sensitivity was 59.6% (28/47), and specificity was 95.7% (89/93) in discriminating the LD type. RFS/OS was significantly shorter in patients with two or more MRI features, compared to those with none or one (310 days vs. 529 days, p = 0.011/964 days vs. 2,023 days, p = 0.010). Conclusions: Preoperative liver MRI may help predict the pathological subtype of iCCAs as either the SD type or LD type, allowing preoperative identification of patients with poorer survival outcomes.

Purpose The purpose of this study is to investigate the physical activity (PA) and exercise barriers of stages 0-3 breast cancer survivors according to the Transtheoretical Model (TTM). Methods This cross-sectional study that included data from a total of 295 breast cancer survivors (Age: 52.2±8.2 years, BMI: 23.5±3.3 kg/m2), at Shinchon Severance Hospital, Seoul, Korea. The levels of PA and exercise barriers according to TTM were investigated using questionnaires. Results PA participation increased in the TTM stage. The proportion of participants categorized according to TTM stage differed according to the time since cancer diagnosis: a higher proportion of participants were in pre-contemplation/contemplation within one year after diagnosis, while a higher proportion of participants were in maintenance after three three years since diagnosis. The five most prevalent exercise barriers were fatigue, low level of physical fitness, poor health, lack of interest, and tendency to be physically inactive. Fatigue is the most prevalent exercise barrier regardless of TTM stage, while most exercise barriers tend to reduce as participants are in the preparation/action and maintenance stages. Conclusions In this study, we confirmed that the participants in the maintenance stage were the most active, while the proportion of participants in the TTM stage varied according to time since diagnosis. Since PA and exercise barriers vary according to the TTM stage, the TTM stage may increase PA participation in breast cancer patients.

The aim of this study was to isolate and identify secondary metabolites from Sonchus brachyotus and evaluate their antioxidant and anti-inflammatory activities. In this study, we isolated three flavonoids from a 70% EtOH extract by Medium Pressure Liquid Chromatography (MPLC) and prep-High-Performance Liquid Chromatography (HPLC). To evaluate the biological activities (an-tioxidant and anti-inflammatory) of these flavonoids, their in vitro inhibitory activities against lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation, nitric oxide (NO) production, and prostaglandin E2 (PGE2) secretion were determined. We successfully identified three flavonoids, namely luteolin (1), luteolin-7-O-β-D-glucoside (2), and luteolin-7-O-β-D-glucuronide (3) by spectral analyses. Luteolin (1) at 20 μg/mL inhibited ROS generation, NO production, and PGE2 secretion by 48.6%, 61.28% and 12.10%, respectively, and luteolin-7-O-β-D-glucoside (2) inhibited NO and PGE2 generation by 67.03% and 20.82%, respectively. Luteolin (1) and luteolin-7-O-β-D-glucoside (2) showed similar anti-inflammatory activities; however, luteolin (1) was observed to be a stronger antioxidant. Besides antioxidant and anti-inflammatory activities, S. brachyotus extract containing luteolin (1) and lu-teolin-7-O-β-D-glucoside (2) is considered to possess diverse biological activities. The results indicate that S. brachyotus is an edible medicinal plant, which is believed to be significant resource of functional foods.

Angiotensin I-converting enzyme (ACE) is an important blood pressure regulator. In this study, we aimed to investigate the ACE-inhibitory effects of meroterpenoids isolated from the brown alga, Sargassum macrocarpum, and the molecular mechanisms underlying ACE inhibition. Four fractions of S. macrocarpum were prepared using hexane, chloroform, ethyl acetate, and water as solvents and analyzed for their potential ACE-inhibitory effects. The chloroform fraction showed the strongest ACE-inhibitory effect, with an IC50 value of 0.18 mg/mL. Three meroterpenoids, sargachromenol, 7-methyl sargachromenol, and sargaquinoic acid, were isolated from the chloroform fraction. Meroterpenoids isolated from S. macrocarpum had IC50 values of 0.44, 0.37, and 0.14 mM. The molecular docking study revealed that the ACE-inhibitory effect of the isolated meroterpenoids was mainly attributed to Zn-ion, hydrogen bonds, pi-anion, and pi–alkyl interactions between the meroterpenoids and ACE. These results suggest that S. macrocarpum could be a potential raw material for manufacturing antihypertensive nutraceutical ingredients.

Purpose This study investigated whether the use of ultrasound (US) guidance in transient elastography (TE) improved the technical success and reliability of liver stiffness (LS) measurements and whether 2-dimensional (2D) shear wave elastography (SWE) provided reliable LS measurements if TE measurements failed. Methods In this prospective study, 292 participants (male:female, 189:103; median age, 60 years) with chronic liver disease (CLD) were enrolled. LS was measured via the consecutive use of conventional TE, 2D-SWE, and US-guided TE. The technical success rates and reliable LS measurement rates of the three elastography techniques were compared. The risk factors for TE failure were assessed through univariate and multivariate logistic regression models. Results US-guided TE was associated with a higher technical success rate (281 of 292, 96.2%) and a higher reliable measurement rate (266 of 292, 91.1%) than conventional TE (technical success: 256 of 292, 87.7%; reliable measurements: 231 of 292, 79.1%; P

Purpose This study was aimed to investigate the value of quantitative ultrasound (US) parameters from radiofrequency (RF) data analysis for assessing hepatic steatosis, using controlled attenuation parameter (CAP)-based steatosis grades as the reference standard. Methods We analyzed 243 participants with both B-mode liver US with RF data acquisition and CAP measurements. On B-mode US images, hepatic steatosis was visually scored (0/1/2/3, none/mild/moderate/severe), and the hepatorenal index (HRI) was calculated. From the RF data analysis, the tissue scatter-distribution imaging parameter (TSI-p) and tissue attenuation imaging parameter (TAI-p) of the liver parenchyma were measured. US parameters were correlated with CAP-based steatosis grades (S0/1/2/3, none/mild/moderate/severe) and their diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Multivariate linear regression analysis was performed to identify determinants of TSI-p and TAI-p. Results Participants were classified as having S0 (n=152), S1 (n=54), S2 (n=14), and S3 (n=23) on CAP measurements. TSI-p and TAI-p were significantly correlated with steatosis grades (ρ =0.593 and ρ=-0.617, P

Purpose This study quantified the impact of respiratory motion on liver stiffness measurements according to different shear wave elastography (SWE) techniques and region of interest (ROI) methods, using liver fibrosis phantoms. Methods Three operators measured stiffness values in four phantoms with different stiffness on a moving platform with two SWE techniques (point-SWE [pSWE] and 2-dimensional SWE [2D-SWE]), three types of motion (static mode and moving mode at low and high speeds), and four ROI methods in 2D-SWE (circle, point, box, and multiple). The circular ROI method was used to compare the two SWE techniques. The occurrence of technical failure and unreliable measurements, stiffness values, and measurement time were evaluated. Results Technical failure was observed only in moving mode for pSWE and 2D-SWE (n=1 for both). Unreliable measurements were also only observed in moving mode and were significantly less common in 2D-SWE (n=1) than in pSWE (n=12) (P

Background: Treatment outcomes of laparoscopic liver resection (LLR) and percutaneous radiofrequency ablation (p-RFA) for small single hepatocellular carcinomas (HCCs) have not yet been fully compared. The aim of this study was to compare LLR and p-RFA as first-line treatment options in patients with single nodular HCCs ≤3 cm. Methods: From January 2014 to December 2016, a total of 566 patients with single nodular HCC ≤3 cm treated by either LLR (n = 251) or p-RFA (n = 315) were included. The recurrence-free survival (RFS) and cumulative incidence of local tumor progression (LTP) were estimated using Kaplan-Meier methods and compared using the log-rank test. Treatment outcome of 2 treatment modalities was compared in the subgroup of patients according to the tumor location. Results: There were no significant differences in overall survival between LLR and p-RFA (p = 0.160); however, 3-year RFS was demonstrated to be significantly higher after LLR (74.4%) than after p-RFA (66.0%) (p = 0.013), owing to its significantly lower cumulative incidence of LTP (2.1% at 3 years after LLR vs. 10.0% after p-RFA, p < 0.001). The complication rate of p-RFA was significantly lower than that of LLR (5.1 vs. 10.0%, p = 0.026). LLR also provided significantly better local tumor control than p-RFA for subscapular tumors (3-year LTP rates: 1.9 vs. 8.8%, p = 0.012), perivascular tumors (3-year LTP rates: 0.0 vs. 17.2%, p = 0.007), and tumors located in anteroinfero-lateral liver portions (3-year LTP rates: 0.0 vs. 10.7%, p < 0.001). However, there were no significant differences in LTP rates between LLR and p-RFA for non-subcapsular and non-perivascular tumors (p = 0.482) and for tumors in postero-superior liver portions (p = 0.380). Conclusions: LLR can provide significantly better local tumor control than p-RFA for small single HCCs in subcapsular, perivascular, and anteroinferolateral liver portions and thus may be the preferred treatment option for these tumors.

Introduction: A switching monopolar no-touch radiofrequency ablation (RFA) technique is used for small hepatocellular carcinoma (HCC); however, there have not been any randomized clinical trials comparing this technique to the conventional RFA technique. Objective:This study aims to compare the results of two RFA techniques, and to comparatively identify more effective methods to reduce the progression of local tumors associated with small HCC (≤2.5 cm). Methods: This prospective randomized clinical trial (NCT03375281) recruited a total of 116 participants (M:F, 93:23; 68.3 ± 8.4 years) between October 2016 and September 2017. The primary outcome was the cumulative incidence of local tumor progression (LTP) after RFA. Secondary outcomes included technical success rate, technique efficacy, and RFA procedure characteristics. Kaplan-Meier analysis and the Cox proportional hazard regression model were used. Results: The mean follow-up period was 24.1 months. A sufficient ablative margin was more frequently achieved in the no-touch RFA group (57/60 = 95%) than in the conventional RFA group (50/64 = 78.1%) on immediate follow-up CT (p = 0.01). The cumulative incidence of LTP in the no-touch RFA group was significantly lower than that in the conventional RFA group (p = 0.02). In multivariable analysis, no-touch RFA was the only predictive factor for LTP (p = 0.04, hazard ratio = 0.2, 95% confidence interval = 0.04–0.94). Conclusions: A switching monopolar no-touch RFA technique is a favorable treatment option and provides lower LTP after RFA compared with conventional RFA for small HCC.

Gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can detect early stages of hepatocellular carcinoma (HCC). However, the survival benefit of Gd-EOB-DTPA-enhanced MRI in the surveillance of patients with cirrhosis has not yet been determined. We explored whether the intermittent replacement of ultrasonography (USG) with Gd-EOB-DTPA-enhanced MRI during HCC surveillance improved the clinical outcomes of patients with cirrhosis. We performed a retrospective cohort study of 421 HCC patients who were newly diagnosed during surveillance. Of these patients, 126 (29.9%) underwent surveillance based on Gd-EOB-DTPA-enhanced MRI and USG (USG+MRI group). The patients (295, 70.1%) who did not undergo MRI during surveillance were referred to as the USG group. In the USG+MRI group, 120 (95.2%) of 126 patients were diagnosed with early-stage HCC, whereas 247 (83.7%) of 295 patients were diagnosed with early-stage HCC in the USG group (P = 0.009). The significantly longer overall survival and time to progression in patients in the USG+MRI group compared to the unmatched cohort USG group was consistently observed by inverse probability weighting and propensity score-matched analysis. Gd-EOB-DTPA-enhanced MRI combined surveillance improved the detection of early-stage HCC and clinical outcomes such as overall survival and the time to progression in patients with cirrhosis.

Abstract Background To investigate the potential value of volumetric iodine quantification using preoperative dual-energy computed tomography (DECT) for predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Methods This retrospective study included patients with single HCC treated through surgical resection who underwent preoperative DECT. Quantitative DECT features, including normalized iodine concentration (NIC) to the aorta and mixed-energy CT attenuation value in the arterial phase, were three-dimensionally measured for peritumoral and intratumoral regions: (i) layer-by-layer analysis for peritumoral layers (outer layers 1 and 2; numbered in close order from the tumor boundary) and intratumoral layers (inner layers 1 and 2) with 2-mm layer thickness and (ii) volume of interest (VOI)-based analysis with different volume coverage (tumor itself; VOIO1, tumor plus outer layer 1; VOIO2, tumor plus outer layers 1 and 2; VOII1, tumor minus inner layer 1; VOII2, tumor minus inner layers 1 and 2). In addition, qualitative CT features, including peritumoral enhancement and tumor margin, were assessed. Qualitative and quantitative CT features were compared between HCC patients with and without MVI. Diagnostic performance of DECT parameters of layers and VOIs was assessed using receiver operating characteristic curve analysis. Results A total of 36 patients (24 men, mean age 59.9 ± 8.5 years) with MVI (n = 14) and without MVI (n = 22) were included. HCCs with MVI showed significantly higher NICs of outer layer 1, outer layer 2, VOIO1, and VOIO2 than those without MVI (P = 0.01, 0.04, 0.02, 0.02, respectively). Among the NICs of layers and VOIs, the highest area under the curve was obtained in outer layer 1 (0.747). Qualitative features, including peritumoral enhancement and tumor margin, and the mean CT attenuation of each layer and each VOI were not significantly different between HCCs with and without MVI (both P > 0.05). Conclusions Volumetric iodine quantification of peritumoral and intratumoral regions in arterial phase using DECT may help predict the MVI of HCC.

Background and Aims: Biannual ultrasonography (US) is a current recommendation for hepatocellular carcinoma (HCC) surveillance in a high-risk group. The sensitivity of US, however, has been low in patients with a high risk of developing HCC. We aimed to compare sensitivity for HCC of biannual US and two-phase low-dose computed tomography (LDCT) in patients with a high risk of HCC. Methods: In this prospective single-arm study, participants with an annual risk of HCC greater than 5% (based on a risk index of ≥2.33) and who did not have a history of HCC were enrolled from November 2014 to July 2016. Participants underwent paired biannual US and two-phase LDCT 1–3 times. Two-phase LDCT included arterial and 3-min delayed phases. The sensitivity, specificity, and positive predictive value of HCC detection using US and two-phase LDCT were compared using a composite algorithm as a standard of reference. Results: Of the 139 enrolled participants, 137 underwent both the biannual US and two-phase LDCT at least once and had follow-up images. Among them, 27 cases of HCC (mean size: 14 ± 4 mm) developed in 24 participants over 1.5 years. Two-phase LDCT showed a significantly higher sensitivity (83.3% [20/24] vs. 29.2% [7/24], p < 0.001) and specificity (95.6% [108/113] vs. 87.7% [99/113], p =0.03) than US. A false-positive result was reported in 14 participants at US and 5 participants at two-phase LDCT, resulting in a significantly higher positive predictive value of two-phase LDCT (33.3% [7/21] vs. 80% [20/25], p < 0.001). Conclusions: Patients with a risk index ≥2.33 showed a high annual incidence of HCC development in our study, and two-phase LDCT showed significantly higher sensitivity and specificity for HCC detection than US.

Abstract Background The decision of transarterial chemoembolization (TACE) initiation and/or repetition remains challenging in patients with unresectable hepatocellular carcinoma (HCC). The aim was to develop a prognostic scoring system to guide TACE initiation/repetition. Methods A total of 597 consecutive patients who underwent TACE as their initial treatment for unresectable HCC were included. We derived a prediction model using independent risk factors for overall survival (OS), which was externally validated in an independent cohort (n = 739). Results Independent risk factors of OS included Albumin-bilirubin (ALBI) grade, maximal tumor size, alpha-fetoprotein, and tumor response to initial TACE, which were used to develop a scoring system (“ASAR”). C-index values for OS were 0.733 (95% confidence interval [CI] = 0.570–0.871) in the derivation, 0.700 (95% CI = 0.445–0.905) in the internal validation, and 0.680 (95% CI = 0.652–0.707) in the external validation, respectively. Patients with ASAR

Purpose The purpose of this study was to evaluate the intra-observer reproducibility of ultrasound attenuation imaging (ATI) for the noninvasive assessment of hepatic steatosis in patients with suspected hepatic steatosis and the inter-observer reproducibility in asymptomatic volunteers. Methods This prospective study was approved by our institutional review board and informed consent was obtained from all patients. In group 1, composed of patients with suspected hepatic steatosis (n=143), one abdominal radiologist performed gray-scale ultrasonography and two sessions of ATI. In group 2, composed of healthy volunteers (n=18), three independent sessions of ATI were performed by three abdominal radiologists. The visual degree of hepatic steatosis in all study subjects was graded on a 4-point scale by two independent reviewers using gray-scale ultrasonography. Thereafter, the attenuation coefficient (AC) was correlated with the degree of hepatic steatosis using Spearman rank correlation analysis. Intra-class correlation coefficients (ICCs) were used to assess the intra-observer (group 1) and inter-observer reproducibility (group 2) of ATI measurements. Results For the intra-observer reproducibility of ATI, the ICC was 0.929 (95% confidence interval [CI], 0.901 to 0.949), and the coefficient of variation was 7.1%. Inter-observer reproducibility of ATI measurements showed an ICC of 0.792 (95% CI, 0.549 to 0.916). The AC showed a significant correlation with the visual grade of hepatic steatosis for both reviewers (rho, 0.780 and 0.695; P

A 64-year-old man was treated with sunitinib as a first-line therapy for metastatic renal cell carcinoma. He was given oral sunitinib in cycles of 50 mg once daily for 2 weeks followed by a week off. During the 5th week of treatment right upper quadrant pain developed, but this resolved spontaneously during the 6th week (off treatment). However, on the 8th week of treatment, he was admitted to hospital because the acute right upper quadrant pain recurred with nausea, vomiting, and fever. Acute acalculous cholecystitis was then diagnosed by ultrasonography and CT. In addition, his laboratory findings indicated disseminated intravascular coagulation. Accordingly, sunitinib therapy was discontinued and broad-spectrum antibiotics initiated. He subsequently recovered after emergent percutaneous cholecystostomy. His Naranjo Adverse Drug Reaction Probability Scale score was 7, indicaing a probable association of the event with sunitinib. Suspicion of sunitinib-related acute cholecystitis is required, because, although uncommon, it can be life-threatening.

Purpose The purpose of this study was to prospectively investigate the intra- and inter-observer repeatability of a new 2-dimensional (2D) shear wave elastography (SWE) technique (S-Shearwave Imaging) for assessing liver fibrosis in chronic liver disease patients, and to compare liver stiffness measurements (LSMs) made using 2D-SWE with those made using point SWE (pSWE). Methods This prospective study received institutional review board approval and informed consent was obtained from all patients. Fifty-three chronic liver disease patients were randomly allocated to group 1 (for intra-observer repeatability [n=33]) or group 2 (for inter-observer repeatability [n=20]). In group 1, two 2D-SWE sessions and one pSWE sessions were performed by one radiologist. In group 2, one 2D-SWE session and one pSWE session were performed by the aforementioned radiologist, and a second 2D-SWE session was performed by another radiologist. The intraclass correlation coefficient (ICC) was used to assess intra- and inter-observer reliability. LSMs obtained using 2D-SWE and pSWE were compared and correlated using the paired t test and Pearson correlation coefficient, respectively. Results LSMs made using 2D-SWE demonstrated excellent intra- and inter-observer repeatability (ICC, 0.997 [95% confidence interval, 0.994 to 0.999]) and 0.995 [0.988 to 0.998], respectively). LSMs made using 2D-SWE were significantly different from those made using pSWE (2.1±0.6 m/sec vs. 1.9±0.6 m/sec, P

Purpose The purpose of this study was to compare the sensitivity of MicroFlow Imaging (MFI) with that of color and power Doppler imaging (CDI and PDI, respectively) in detecting the vascularity of hepatocellular carcinomas (HCCs). Methods This prospective study enrolled 51 patients diagnosed with HCC between August 2018 and December 2018. CDI, PDI, MFI, and contrast-enhanced ultrasound (CEUS) were performed. Two radiologists evaluated the presence and pattern of tumoral vascularity on CDI, PDI, and MFI. Vascular presence was graded on a 5-point scale (0, absent; 4, >50% of the tumor). The vascular pattern was chosen from following categories: basket, vessels in tumor, spot, detouring, mixed, or others. Two additional radiologists assessed CEUS images for the presence and pattern of tumoral vascularity, which served as the reference standard. If the tumoral vascular pattern on each examination matched that of the CEUS images, the Wilcoxon test and McNemar test, respectively, were used to compare the sensitivity for detecting tumoral vascularity between MFI and CDI, and between MFI and PDI. Logistic regression analysis was performed to identify factors associated with MFI detectability of tumoral vascularity. Results CEUS demonstrated tumoral vascularity in 98.0% (50 of 51) of patients. MFI (58.0%, 29 of 50) demonstrated a higher sensitivity than CDI (14.0%, 7 of 50) or PDI (14.0%, 7 of 50) (P

Abstract Background The Liver Imaging Reporting and Data System (LI-RADS) and European Association for the Study of the Liver (EASL) criteria are widely used for diagnosing hepatocellular carcinoma (HCC). Radiomics allows further quantitative tumor heterogeneity profiling. This study aimed to compare the diagnostic accuracies of the version 2018 (v2018) EASL, LI-RADS criteria and radiomics models for HCC in high-risk patients. Methods Ethical approval by the institutional review board and informed consent were obtained for this study. From July 2015 to September 2018, consecutive high-risk patients were enrolled in our tertiary care hospital and underwent gadoxetic acid-enhanced magnetic resonance (MR) imaging and subsequent hepatic surgery. We constructed a multi-sequence-based three-dimensional whole-tumor radiomics signature by least absolute shrinkage and selection operator model and multivariate logistic regression analysis. The diagnostic accuracies of the radiomics signature was validated in an independent cohort and compared with the EASL and LI-RADS criteria reviewed by two independent radiologists. Results Two hundred twenty-nine pathologically confirmed nodules (173 HCCs, mean size: 5.74 ± 3.17 cm) in 211 patients were included. Among them, 201 patients (95%) were infected with hepatitis B virus (HBV). The sensitivity and specificity were 73 and 71% for the radiomics signature, 91 and 71% for the EASL criteria, and 86 and 82% for the LI-RADS criteria, respectively. The areas under the receiver operating characteristic curves (AUCs) of the radiomics signature (0.810), LI-RADS (0.841) and EASL criteria (0.811) were comparable. Conclusions In HBV-predominant high-risk patients, the multi-sequence-based MR radiomics signature, v2018 EASL and LI-RADS criteria demonstrated comparable overall accuracies for HCC.

Abstract Background In order to assess the high value-added use of the alginate-free residue of sea tangle, an animal study was performed to evaluate the functional activities and key compounds present. In the animal study, sea tangle and the alginate-free residue demonstrated good anti-hyperlipidemic and anti-arteriosclerotic abilities. Results The functional compounds in the alginate-free residue of the sea tangle were effectively extracted by supercritical fluid extraction (SFE). The optimum extraction temperature and pressure were 40 °C and 6500 psi (M1) in the SFE, a better method in comparison to the conditions of 70 °C and 4500 psi (M2), respectively. The anti-atherosclerotic effects of the alginate-free residue of sea tangle (M1, M2) were investigated in Sprague-Dawley rats treated with poloxamer 407, Triton WR 1339, corn oil, and a high-fat diet. The M1 fraction reduced the serum lipid levels with greater efficacy than the M2 fraction. In the hyperlipidemic rats, treatment with M1 decreased the serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) levels when compared to the levels in normal rats. Conclusion Our results demonstrated that the alginate-free residue of sea tangle reduces serum TC, TG, and LDL-C. These results suggest that the alginate-free residue of sea tangle contains physiologically active components, such as fucosterol, that may exert beneficial effects in the prevention of atherosclerosis.