• Korean Journal of Radiology
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• v.21 no.4
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• pp.402-412
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• 2020

Objective: To evaluate the performance of predicting early recurrence using preoperative factors only in comparison with using both pre-/postoperative factors. Materials and Methods: We retrospectively reviewed 549 patients who had undergone curative resection for single hepatcellular carcinoma (HCC) within Milan criteria. Multivariable analysis was performed to identify pre-/postoperative high-risk factors of early recurrence after hepatic resection for HCC. Two prediction models for early HCC recurrence determined by stepwise variable selection methods based on Akaike information criterion were built, either based on preoperative factors alone or both pre-/postoperative factors. Area under the curve (AUC) for each receiver operating characteristic curve of the two models was calculated, and the two curves were compared for non-inferiority testing. The predictive models of early HCC recurrence were internally validated by bootstrap resampling method. Results: Multivariable analysis on preoperative factors alone identified aspartate aminotransferase/platelet ratio index (OR, 1.632; 95% CI, 1.056-2.522; p = 0.027), tumor size (OR, 1.025; 95% CI, 0.002-1.049; p = 0.031), arterial rim enhancement of the tumor (OR, 2.350; 95% CI, 1.297-4.260; p = 0.005), and presence of nonhypervascular hepatobiliary hypointense nodules (OR, 1.983; 95% CI, 1.049-3.750; p = 0.035) on gadoxetic acid-enhanced magnetic resonance imaging as significant factors. After adding postoperative histopathologic factors, presence of microvascular invasion (OR, 1.868; 95% CI, 1.155-3.022; p = 0.011) became an additional significant factor, while tumor size became insignificant (p = 0.119). Comparison of the AUCs of the two models showed that the prediction model built on preoperative factors alone was not inferior to that including both pre-/postoperative factors {AUC for preoperative factors only, 0.673 (95% confidence interval [CI], 0.623-0.723) vs. AUC after adding postoperative factors, 0.691 (95% CI, 0.639-0.744); p = 0.0013}. Bootstrap resampling method showed that both the models were valid. Conclusion: Risk stratification solely based on preoperative imaging and laboratory factors was not inferior to that based on postoperative histopathologic risk factors in predicting early recurrence after curative resection in within Milan criteria single HCC patients.

• Korean Journal of Radiology
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• v.22 no.2
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• pp.213-224
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• 2021

Objective: Clinical outcomes of patients who undergo transarterial chemoembolization (TACE) for single small hepatocellular carcinoma (HCC) are not consistent, and may differ based on certain imaging findings. This retrospective study was aimed at determining the efficacy of pre-TACE CT or MR imaging findings in predicting survival outcomes in patients with small HCC upon being treated with TACE. Besides, the study proposed to build a risk prediction model for these patients. Materials and Methods: Altogether, 750 patients with functionally good hepatic reserve who received TACE as the first-line treatment for single small HCC between 2004 and 2014 were included in the study. These patients were randomly assigned into training (n = 525) and validation (n = 225) sets. Results: According to the results of a multivariable Cox analysis, three pre-TACE imaging findings (tumor margin, tumor location, enhancement pattern) and two clinical factors (age, serum albumin level) were selected and scored to create predictive models for overall, local tumor progression (LTP)-free, and progression-free survival in the training set. The median overall survival time in the validation set were 137.5 months, 76.1 months, and 44.0 months for low-, intermediate-, and high-risk groups, respectively (p < 0.001). Time-dependent receiver operating characteristic curves of the predictive models for overall, LTP-free, and progression-free survival applied to the validation cohort showed acceptable areas under the curve values (0.734, 0.802, and 0.775 for overall survival; 0.738, 0.789, and 0.791 for LTP-free survival; and 0.671, 0.733, and 0.694 for progression-free survival at 3, 5, and 10 years, respectively). Conclusion: Pre-TACE CT or MR imaging findings could predict survival outcomes in patients with small HCC upon treatment with TACE. Our predictive models including three imaging predictors could be helpful in prognostication, identification, and selection of suitable candidates for TACE in patients with single small HCC.

• Progress in Medical Physics
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• v.9 no.3
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• pp.155-162
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• 1998

Ho-l66 was produced by neutron reaction in a reactor at the Korea Atomic Energy Institute (Taejon, Korea). Ho-l66 emits a high energy beta particles with a maximum energy of 1.85 MeV and small proportion of gamma rays (80 keV). Therefore, the radiation absorbed dose estimation could be based on the in-vivo quantification of the activity in tumors from the gamma camera images. Approximately 1 mCi of Ho-l66 in solution was mixed into the flood phantom and planar scintigraphic images were acquired with and without patient interposed between the phantom and scintillation camera. Transmission factor over an area of interest was calculated from the ratio of counts in selected regions of the two images described above. A dual-head gamma camera(Multispect2, Siemens, Hoffman Estates, IL, USA) equipped with medium energy collimators was utilized for imaging(80 keV${\pm}$10%). Fifty-nine year old female patient with hepatoma was enrolled into the therapeutic protocol after the informed consent obtained. Thirty millicuries(110MBq) of Ho-166-CHICO was injected into the right hepatic arterial branch supplying hepatoma. When the injection was completed, anterior and posterior scintigraphic views of the chest and pelvic regions were obtained for 3 successive days. Regions of interest (ROIs) were drawn over the organs in both the anterior and posterior views. The activity in those ROIs was estimated from geometric mean, calibration factor and transmission factors. Absorbed dose was calculated using the Marinelli formula and Medical Internal Radiation Dose (MIRD) schema. Tumor dose of the patient treated with 1110 MBq(30 mCi) Ho-l66 was calculated to be 179.7 Gy. Dose distribution to normal liver, spleen, lung and bone was 9.1, 10.3, 3.9, 5.0 % of the tumor dose respectively. In conclusion, tumor dose and absorbed dose to surrounding structures were calculated by daily external imaging after the Ho-l66 therapy for hepatoma. In order to limit the thresholding dose to each surrounding organ, absorbed dose calculation provides useful information.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.2
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• pp.227-236
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• 2010

This study was carried out to investigate the anti-oxidative and anti-inflammatory actions of Hericium erinaceus mycelia in BALB/C mice injected with lopopolysaccharide (LPS), called endotoxin. Mice (6 weeks of age) weighing approximately $24.73\pm0.11$ g were divided into 5 groups and were fed on the experimental diets containing Hericium erinaceus mycelia powder (HMP) for 1 week. Experimental groups were NC (normal control), HMP-C (HMP control), LC (LPS control), HMP 3%, and HMP 10%. Endotoxin shock was induced by intraperitoneal injection of LPS (100 mg/kg BW). NC and HMP-C groups were injected with saline solution (100 mg/kg BW). Food efficiency ratio were significantly (p<0.05) decreased in the HMP supplementation groups. Total fat and $\beta$-glucan excretion were higher in HMP supplementation groups than NC and LC groups, while plasma TG level was not different among groups. Plasma ALT levels were significantly (p<0.05) lower in the HMP supplementation groups than in LC group at 8 hr after LPS injection, while tumor necrosis factor-$\alpha$ and interleukine-6 levels of plasma were not different among groups. Hepatic superoxide dismutase, glutathione-reductase (GSH-red), and glutathione-peroxidase activities were higher in the HMP supplementation groups than in LC group at 4 hr after intraperitoneal injection of LPS. Hepatic GSH levels and protein expression of GSH-red was significantly (p<0.05) higher in the HMP supplemented groups than in LC group at 1 hr, 4 hr and 8 hr after LPS injection. From the above results, it is concluded that Hericium erinaceus mycelia may ameliorate hepatic oxidative stress by LPS through the elevation of hepatic glutathione level and antioxidant enzyme activities, which support the hepatoprotective effect of Hericium erinaceus mycelia.

• Investigative Magnetic Resonance Imaging
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• v.21 no.2
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• pp.71-81
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• 2017

Purpose: To compare three, motion-resistant, T1-weighted MR sequences on the hepatobiliary phase for gadoxetic acid-enhanced MR imaging of the liver. Materials and Methods: In this retrospective study, 79 patients underwent gadoxetic acid-enhanced, 3T liver MR imaging. Fifty-nine were examined using a standard protocol, and 20 were examined using a motion-resistant protocol. During the hepatocyte-specific phase, three MR sequences were acquired: 1) gradient recalled echo (GRE) with controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA); 2) radial GRE with the interleaved angle-bisection scheme (ILAB); and 3) radial GRE with golden-angle scheme (GA). Two readers independently assessed images with motion artifacts, streaking artifacts, liver-edge sharpness, hepatic vessel clarity, lesion conspicuity, and overall image quality, using a 5-point scale. The images were assessed by measurement of liver signal-to-noise ratio (SNR), and tumor-to-liver contrast-to-noise ratio (CNR). The results were compared, using repeated post-hoc, paired t-tests with Bonferroni correction and the Wilcoxon signed rank test with Bonferroni correction. Results: In the qualitative analysis of cooperative patients, the results for CAIPIRINHA had significantly higher ratings for streak artifacts, liver-edge sharpness, hepatic vessel clarity, and overall image quality as compared to, radial GRE, (P < 0.016). In the imaging of uncooperative patients, higher scores were recorded for ILAB and GA with respect to all of the qualitative assessments, except for streak artifact, compared with CAIPIRINHA (P < 0.016). However, no significant differences were found between ILAB and GA. For quantitative analysis in uncooperative patients, the mean liver SNR and lesion-to-liver CNR with radial GRE were significantly higher than those of CAIPIRINHA (P < 0.016). Conclusion: In uncooperative patients, the use of the radial GRE sequence can improve the image quality compared to GRE imaging with CAIPIRINHA, despite the data acquisition methods used. The GRE imaging with CAIPIRINHA is applicable for patients without breath-holding difficulties.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.197-202
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• 2008

In our previous publication we compared the gene expression profiles on hepatotoxicants exposure to assess the comparability between in vivo and in vitro test systems. We investigated global gene expression from both mouse liver and mouse hepatic cell line treated with thioacetamide (TAA) and identified several common genes. In this study, we selected genes to validate them as potential biomarkers for hepatotoxicity on the relevance of in vitro and in vivo system. Three up-regulated, aquaporin 8 (Aqp8), glutathione peroxidase 1 (Gpx1), succinate-CoA ligase, GDP-forming, alpha subunit (Suclg1) and two down-regulated, DnaJ (Hsp40) homolog subfamily C member 5 (Dnajc5) and tumor protein D52 (Tpd52) genes were tested for their effects in vitro. For characterization of gene function, short interfering RNA (siRNA) for each gene was synthesized and transfected in mouse hepatic cell line, BNL CL.2. Cell viability, mRNA expression level and morphological alterations were investigated. We confirmed siRNA transfection against selected five genes induced down-regulation of respective mRNA expression. siRNA transfection in general decreased cell viability in different degrees and induced morphological changes such as membrane thickening and alterations of intracellular structures. This suggests that these genes could be associated with TAA-induced toxicity. Furthermore, these genes may be used in the investigation of hepatotoxicity for better understanding of its mechanism.

• Nutrition Research and Practice
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• v.14 no.3
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• pp.175-187
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• 2020

BACKGROUND/OBJECTIVES: In this study, we investigated the beneficial effects of skate cartilage extracts containing chondroitin sulfate (SCS) on hyperlipidemia-induced inflammation and oxidative stress in high cholesterol diet (HCD)-fed mice in comparison with the effects of shark cartilage-derived chondroitin sulfate (CS). MATERIALS/METHODS: Low-density lipoprotein receptor knockout (LDLR-KO) mice were fed HCD with an oral administration of CS (50 and 100 mg/kg BW/day), SCS (100 and 200 mg/kg BW/day), or water, respectively, for ten weeks. RESULTS: The administration of CS or SCS reduced the levels of serum triglyceride (TG), total cholesterol (TC), and LDL cholesterol and elevated the levels of high-density lipoprotein cholesterol, compared with those of the control group (P < 0.05). Furthermore, CS or SCS significantly attenuated inflammation by reducing the serum levels of interleukin (IL)-1β and hepatic protein expression levels of nuclear factor kappa B, inducible nitric oxide synthase, cyclooxygenase-2, and IL-1beta (P < 0.05). In particular, the serum level of tumor necrosis factor-alpha was reduced only in the 100 mg/kg BW/day of SCS-fed group, whereas the IL-6 level was reduced in the 100 and 200 mg/kg BW/day of SCS-fed groups (P < 0.05). In addition, lipid peroxidation and nitric oxide production were attenuated in the livers of the CS and SCS groups mediated by the upregulation of hepatic proteins of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase (P < 0.05). CONCLUSIONS: These results suggest that the biological effects of SCS, similar to those of CS, are attributed to improved lipid profiles as well as suppressed inflammation and oxidative stress induced by the intake of HCD.

• Journal of Life Science
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• v.18 no.11
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• pp.1551-1560
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• 2008

Cytokines play a pivotal role in systemic inflammatory response following cardiac surgery with cardiopulmonary bypass (CPB). The purpose of this study was to investigate the perioperative changes in proinflammatory [tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-6 (IL-6)] and antiinflammatory cytokines [interleukin-10 (IL-10)], and each correlation between the cytokines and other variables in valvular heart surgery with CPB. Serum IL-6 and IL-10 levels and leukocyte counts significantly increased following CPB. CPB caused hepatic, renal and myocardial dysfunctions. IL-6 levels had positive correlations with IL-10 levels at postoperative periods. TNF-$\alpha$ levels had correlations with leukocyte counts and myocardial marker levels at postoperative 24 hr (PO-24 h). Furthermore, IL-6 or IL-10 levels had positive correlations with other variable such as hepatic, renal or myocardial marker at postoperative periods. These results showed that balance between proinflammatory and antiinflammatory cytokines is maintained during cardiac surgery with CPB, and that these cytokines exert postoperatively inflammatory and antiinflammatory reactions.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.109-117
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• 1993

To analyze biochemical changes of liver function following combined radiotherapy and hyperthermia, we reviewed retrospectively 37 patients with hepatocellular carcinoma treated with radiotherapy and hyperthermia between July 1988 and December 1990 at Department of Radiation Oncology, Yonsei University College of Medicine. Mean age was 52.7 years and male to female ratio was 11:1. The patients were classified as follows; to A and B group by Child's classification, to M and L group by irradiated volume, and subclassified into BM, BL, AM and AL group according to the combination of Child's classification and irradiated volume. Radiation dose to the primary tumor was 3060 cGy with daily 180 cGy, 5 fraction per week using 10 MV or 4 MV linear accelerator. Hyperthermia (Thermotron RF-8) was performed more than 4 times in all patients. Biochemical parameters including albumin (Alb), total bilirubin (T. Bil), aspartate aminotransferase (AST or SGOT), alanine aminotransferase (ALT or SGPT), and alkaline phosphatase (ALP) were regularly followed from 1 week before the treatment to 3 months after the treatment. The results are summerized as follows; 1) In all the patient, mean ALP level peaked at 1 month, decreased at 2 months, slightly increased at 3 months after the treatment. Mean SGOT and SGPT levels peaked at 1 month after the treatment. Mean T. Bil level increased continuously and highest at 3 months after the treatment. Mean Alb level did not show significant changes.; 2) Mean ALP level retured to normal level at 3 month after the treatment in A but increased in B group and the differences were statistically significant (p<0.01). Mean SGOT and SGPT levels peaked 1 month in A and 2 months after the treatment in B group. All the biochemical parameters did not show significant difference between M and L group. Mean ALP level increased at 3 months after the treatment in BM and BL groups and decreased in AM and AL groups. Mean SGOT level increased at 3 months after the treatment in BL groups.; 3) Hepatic failure occurred within 3 months after the treatment in 4 patients, all of whom were in BL group. It is suggested that pre-treatment liver function and irradiated volume influence biochemical changes of liver in patients with hepatocellular carcinoma following combined radiotherapy and hyperthermia, and this treatment modality appears generally to be safe but might cause hepatic failure particularly in patient with poor liver function and large treatment volume.

• Nutrition Research and Practice
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• v.16 no.6
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• pp.729-744
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• 2022

BACKGROUND/OBJECTIVES: 4-Hydroxy-2-nonenal (HNE) is a biomarker for oxidative stress to induce inflammation. Methionine is an essential sulfur-containing amino acid with antioxidative activity. On the other hand, the evidence on whether and how methionine can depress HNE-derived inflammation is lacking. In particular, the link between the regulation of the nuclear factor-κB (NF-κB) signaling pathway and methionine intake is unclear. This study examined the link between depression from HNE accumulation and the anti-inflammatory function of ⳑ-methionine in rats. MATERIALS/METHODS: Male Wistar rats (3-week-old, weighing 70-80 g) were administered different levels of ⳑ-methionine orally at 215.0, 268.8, 322.5, and 430.0 mg/kg body weight for two weeks. The control group was fed commercial pellets. The hepatic HNE contents and the protein expression and mRNA levels of the inflammatory mediators were measured. The interleukin-10 (IL-10) and glutathione S-transferase (GST) levels were also estimated. RESULTS: Compared to the control group, hepatic HNE levels were reduced significantly in all groups fed ⳑ-methionine, which were attributed to the stimulation of GST by ⳑ-methionine. With decreasing HNE levels, ⳑ-methionine inhibited the activation of NF-κB by up-regulating inhibitory κBα and depressing phosphoinositide 3 kinase/protein kinase B. The mRNA levels of the inflammatory mediators (cyclooxygenase-2, interleukin-1β, interleukin-6, inducible nitric oxide synthase, tumor necrotic factor alpha) were decreased significantly by ⳑ-methionine. In contrast, the protein expression of these inflammatory mediators was effectively down regulated by ⳑ-methionine. The anti-inflammatory action of ⳑ-methionine was also reflected by the up-regulation of IL-10. CONCLUSIONS: This study revealed a link between the inhibition of HNE accumulation and the depression of inflammation in growing rats, which was attributed to ⳑ-methionine availability. The anti-inflammatory mechanism exerted by ⳑ-methionine was to inhibit NF-κB activation and to up-regulate GST.