Publications by authors named "Jeong Hoon Lee"

585 Publications

Policy Design for an Ankle-Foot Orthosis Using Simulated Physical Human-Robot Interaction via Deep Reinforcement Learning.

IEEE Trans Neural Syst Rehabil Eng 2022 11;30:2186-2197. Epub 2022 Aug 11.

This paper presents a novel approach for designing a robotic orthosis controller considering physical human-robot interaction (pHRI). Computer simulation for this human-robot system can be advantageous in terms of time and cost due to the laborious nature of designing a robot controller that effectively assists humans with the appropriate magnitude and phase. Therefore, we propose a two-stage policy training framework based on deep reinforcement learning (deep RL) to design a robot controller using human-robot dynamic simulation. In Stage 1, the optimal policy of generating human gaits is obtained from deep RL-based imitation learning on a healthy subject model using the musculoskeletal simulation in OpenSim-RL. In Stage 2, human models in which the right soleus muscle is weakened to a certain severity are created by modifying the human model obtained from Stage 1. A robotic orthosis is then attached to the right ankle of these models. The orthosis policy that assists walking with optimal torque is then trained on these models. Here, the elastic foundation model is used to predict the pHRI in the coupling part between the human and robotic orthosis. Comparative analysis of kinematic and kinetic simulation results with the experimental data shows that the derived human musculoskeletal model imitates a human walking. It also shows that the robotic orthosis policy obtained from two-stage policy training can assist the weakened soleus muscle. The proposed approach was validated by applying the learned policy to ankle orthosis, conducting a gait experiment, and comparing it with the simulation results.
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http://dx.doi.org/10.1109/TNSRE.2022.3196468DOI Listing
August 2022

Correlation between Results of Semi-Quantitative and Quantitative Tests for Hepatitis B Virus Surface Antigen among Patients Achieving Viral Suppression with Antiviral Treatment.

Diagnostics (Basel) 2022 Jul 20;12(7). Epub 2022 Jul 20.

Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.

: Hepatitis B virus (HBV) infection remains a threat to global public health. Serum hepatitis B surface antigen (HBsAg) has been used in screening for HBV infection. Quantitative HBsAg assays are useful for monitoring the natural history of HBV infection and its response to therapy. The aim of this study was to determine the relationship between quantitative (qHBsAg; IU/mL) and semi-quantitative (sqHBsAg; signal-to-cutoff ratio [S/Co]) HBsAg titers in patients with chronic hepatitis B (CHB). : We retrospectively included 284 samples with HBV DNA < 20 IU/mL from patients who had simultaneous qHBsAg (using electrochemiluminescence assay) and sqHBsAg tests. Patients were grouped according to their serum HBV-envelope antigen (HBeAg) status (HBeAg-negative, = 239 and HBeAg-positive, = 45). The Spearman test was used to analyze the correlation between the quantitative and semi-quantitative assays. : There was a significant linear correlation between sqHBsAg and qHBsAg in the HBeAg-negative patients (qHBsAg [IU/mL] = 0.0094 × sqHBsAg [S/Co]; adjusted R = 0.8445; < 0.001). There was a substantial hook effect in the assays from the HBeAg-positive patients, so we performed a stratified analysis according to qHBsAg <1000 IU/mL or ≥1000 IU/mL and found a significant positive linear correlation between sqHBsAg S/Co and qHBsAg (qHBsAg [IU/mL] = 0.072 × sqHBsAg [S/Co]; adjusted R = 0.7878; < 0.001) in HBeAg-positive patients with qHBsAg titers of <1000 IU/mL and a significant negative correlation in HBeAg-positive patients with qHBsAg titers of ≥1000 IU/mL (qHBsAg [IU/mL] = 8.987 × 10 × sqHBsAg [S/Co]; adjusted R = 0.6350; < 0.001). : There was a highly linear, positive correlation between qHBsAg and sqHBsAg in HBeAg-negative CHB patients. The hook effect led to a negative correlation in HBeAg-positive CHB patients with qHBsAg titers ≥1000 IU/mL.
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http://dx.doi.org/10.3390/diagnostics12071757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317496PMC
July 2022

Real-Time Polymerase Chain Reaction for the Detection of and Clarithromycin Resistance.

Gut Liver 2022 Jul 20. Epub 2022 Jul 20.

Department of Microbiology, Hanyang University College of Medicine, Seoul, Korea.

Background/aims: Real-time polymerase chain reaction (RT-PCR) is a fast and simple method for the simultaneous detection of clarithromycin (CLR) resistance and . We evaluated the effectiveness of RT-PCR compared to that of the rapid urease test (RUT) and assessed its value in verifying CLR resistance.

Methods: A total of 70 specimens with confirmed infection in culture were enrolled and analyzed in this prospective study. All specimens were subjected to RT-PCR assay using fluorescence melting peak signals to detect infection and CLR resistances caused by either A2142G or A2143G mutations in the 23S ribosomal RNA gene (23S rRNA). The results were compared to those of RUT and antimicrobial susceptibility culturing tests to investigate the efficacy of RT-PCR.

Results: Among the 70 specimens analyzed, the positivity rate was 97.1% (68/70) with RT-PCR and 82.9% (58/70) with RUT. CLR resistance (minimum inhibitory concentration >1.0 μg/mL) was confirmed in 18.6% (13/70), and fluorescence melting curve analysis showed that 84.6% (11/13) had point mutations in 23S rRNA. Ten specimens had only A2143G mutation, and one specimen contained both A2142G and A2143G mutations.

Conclusions: RT-PCR assay was found to be more efficient than RUT in detecting infection and could effectively verify CLR resistance compared to the antimicrobial susceptibility culturing test. Considering the high sensitivity and accessibility of RT-PCR method, it could be used to easily detect CLR-resistant , thus helping clinicians select suitable treatment regimen and improve the eradication rate.
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http://dx.doi.org/10.5009/gnl220076DOI Listing
July 2022

Development and Validation of a Multimodal-Based Prognosis and Intervention Prediction Model for COVID-19 Patients in a Multicenter Cohort.

Sensors (Basel) 2022 Jul 2;22(13). Epub 2022 Jul 2.

Department of Radiology, Gil Medical Center, Gachon University College of Medicine, Namdong-daero 774 beon-gil, Namdong-gu, Incheon 21565, Korea.

The ability to accurately predict the prognosis and intervention requirements for treating highly infectious diseases, such as COVID-19, can greatly support the effective management of patients, especially in resource-limited settings. The aim of the study is to develop and validate a multimodal artificial intelligence (AI) system using clinical findings, laboratory data and AI-interpreted features of chest X-rays (CXRs), and to predict the prognosis and the required interventions for patients diagnosed with COVID-19, using multi-center data. In total, 2282 real-time reverse transcriptase polymerase chain reaction-confirmed COVID-19 patients' initial clinical findings, laboratory data and CXRs were retrospectively collected from 13 medical centers in South Korea, between January 2020 and June 2021. The prognostic outcomes collected included intensive care unit (ICU) admission and in-hospital mortality. Intervention outcomes included the use of oxygen (O) supplementation, mechanical ventilation and extracorporeal membrane oxygenation (ECMO). A deep learning algorithm detecting 10 common CXR abnormalities (DLAD-10) was used to infer the initial CXR taken. A random forest model with a quantile classifier was used to predict the prognostic and intervention outcomes, using multimodal data. The area under the receiver operating curve (AUROC) values for the single-modal model, using clinical findings, laboratory data and the outputs from DLAD-10, were 0.742 (95% confidence interval [CI], 0.696-0.788), 0.794 (0.745-0.843) and 0.770 (0.724-0.815), respectively. The AUROC of the combined model, using clinical findings, laboratory data and DLAD-10 outputs, was significantly higher at 0.854 (0.820-0.889) than that of all other models ( < 0.001, using DeLong's test). In the order of importance, age, dyspnea, consolidation and fever were significant clinical variables for prediction. The most predictive DLAD-10 output was consolidation. We have shown that a multimodal AI model can improve the performance of predicting both the prognosis and intervention in COVID-19 patients, and this could assist in effective treatment and subsequent resource management. Further, image feature extraction using an established AI engine with well-defined clinical outputs, and combining them with different modes of clinical data, could be a useful way of creating an understandable multimodal prediction model.
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http://dx.doi.org/10.3390/s22135007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269794PMC
July 2022

Feasibility study of a novel rectal cooling system for hypothermic radical prostatectomy in a swine model.

Investig Clin Urol 2022 Jul;63(4):475-481

Department of Urology, Seoul National University Hospital, Seoul, Korea.

Thermal damage and inflammatory responses of the sphincter and neurovascular bundles (NVBs) are responsible for post-prostatectomy incontinence and erectile dysfunction. Intraoperative hypothermia in the pelvic cavity may reduce the occurrence of these complications. We evaluated the feasibility of a novel rectal cooling system using an animal model. A novel rectal cooling system consisting of a cooling console and a multi-lumen rectal balloon was developed. We conducted animal tests on male pigs to evaluate the efficacy and safety of the system. The primary endpoint was to maintain the temperature of the NVBs at 25℃ (±5℃) during and after the electrocauterization of the bladder neck for 10 seconds. The safety endpoint was device-related complications or significant changes in the core body temperature of the pigs. The NVB temperature was below 30℃ within 3 minutes of activation of the rectal balloon. The temperature of the proximal NVB was consistently maintained below 25℃ in all cases. The temperature 1 cm from the bladder neck did not rise above 38℃ and dropped to the initial level within 1 minute after electrocauterization. During cooling, the minimum temperature at the apex of the prostate was reduced to 10.1℃. There were no device-related complications or significant changes in core body temperature throughout the experiment. Animal tests suggest the feasibility and safety of this novel rectal cooling system. A first-in-human trial to assess the safety and efficacy of this system during radical prostatectomy is warranted.
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http://dx.doi.org/10.4111/icu.20220092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262486PMC
July 2022

Natural History of Asymptomatic Esophageal Subepithelial Tumors of 30 mm or Less in Size.

J Korean Med Sci 2022 Jun 13;37(23):e184. Epub 2022 Jun 13.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: No definite guidelines for the management of small esophageal subepithelial tumors (SETs) have been established, because there are limited data and studies on their natural history. We aimed to assess the natural history and propose optimal management strategies for small esophageal SETs.

Methods: Patients diagnosed as esophageal SETs ≤ 30 mm in size between 2003 and 2017 using endoscopic ultrasound (EUS) with a minimal follow-up of 3 months were enrolled, and their esophagogastroduodenoscopy (EGD) and EUS were retrospectively reviewed.

Results: Of 275 esophageal SETs in 262 patients, the initial size was < 10 mm, 10-20 mm, and 20-30 mm in 104 (37.8%), 105 (38.2%), and 66 (24.0%) lesions, respectively. Only 22 (8.0%) SETs showed significant changes in size and/or echogenicity and/or morphology at a median of 40 months (range, 4-120 months). Tissues of 6 SETs showing interval changes were obtained using EUS-guided fine needle aspiration biopsy; 1 was identified as a gastrointestinal stromal tumor (GIST) and was surgically resected, while the other 5 were leiomyomas and were regularly observed. Eight SETs showing interval changes were resected surgically or endoscopically without pathological confirmation; 1 was a GIST, 2 were granular cell tumors, and the other 5 were leiomyomas.

Conclusion: Regular follow-up with EGD or EUS may be necessary for esophageal SETs ≤ 30 mm in size considering that small portion of them has a possibility of malignant potential. When esophageal SETs ≤ 30 mm show significant interval changes, pathological confirmation may precede treatment to avoid unnecessary resection.
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http://dx.doi.org/10.3346/jkms.2022.37.e184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194489PMC
June 2022

Clinicoradiological Characteristics in the Differential Diagnosis of Follicular-Patterned Lesions of the Thyroid: A Multicenter Cohort Study.

Korean J Radiol 2022 07 31;23(7):763-772. Epub 2022 May 31.

Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Objective: Preoperative differential diagnosis of follicular-patterned lesions is challenging. This multicenter cohort study investigated the clinicoradiological characteristics relevant to the differential diagnosis of such lesions.

Materials And Methods: From June to September 2015, 4787 thyroid nodules (≥ 1.0 cm) with a final diagnosis of benign follicular nodule (BN, n = 4461), follicular adenoma (FA, n = 136), follicular carcinoma (FC, n = 62), or follicular variant of papillary thyroid carcinoma (FVPTC, n = 128) collected from 26 institutions were analyzed. The clinicoradiological characteristics of the lesions were compared among the different histological types using multivariable logistic regression analyses. The relative importance of the characteristics that distinguished histological types was determined using a random forest algorithm.

Results: Compared to BN (as the control group), the distinguishing features of follicular-patterned neoplasms (FA, FC, and FVPTC) were patient's age (odds ratio [OR], 0.969 per 1-year increase), lesion diameter (OR, 1.054 per 1-mm increase), presence of solid composition (OR, 2.255), presence of hypoechogenicity (OR, 2.181), and presence of halo (OR, 1.761) (all < 0.05). Compared to FA (as the control), FC differed with respect to lesion diameter (OR, 1.040 per 1-mm increase) and rim calcifications (OR, 17.054), while FVPTC differed with respect to patient age (OR, 0.966 per 1-year increase), lesion diameter (OR, 0.975 per 1-mm increase), macrocalcifications (OR, 3.647), and non-smooth margins (OR, 2.538) (all < 0.05). The five important features for the differential diagnosis of follicular-patterned neoplasms (FA, FC, and FVPTC) from BN are maximal lesion diameter, composition, echogenicity, orientation, and patient's age. The most important features distinguishing FC and FVPTC from FA are rim calcifications and macrocalcifications, respectively.

Conclusion: Although follicular-patterned lesions have overlapping clinical and radiological features, the distinguishing features identified in our large clinical cohort may provide valuable information for preoperative distinction between them and decision-making regarding their management.
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http://dx.doi.org/10.3348/kjr.2022.0079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240300PMC
July 2022

Outcomes of endoscopic submucosal dissection for superficial esophageal neoplasms in patients with liver cirrhosis.

Clin Endosc 2022 May 20;55(3):381-389. Epub 2022 Apr 20.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background/aims: The treatment of superficial esophageal neoplasms (SENs) in cirrhotic patients is challenging and rarely investigated. We evaluated the outcomes of endoscopic submucosal dissection (ESD) to determine the efficacy and safety of treating SENs in patients with liver cirrhosis.

Methods: The baseline characteristics and treatment outcomes of patients who underwent ESD for SENs between November 2005 and December 2017 were retrospectively reviewed.

Results: ESD was performed in 437 patients with 481 SENs, including 15 cirrhotic patients with 17 SENs. En bloc resection (88.2% vs. 97.0%) and curative resection (64.7% vs. 78.9%) rates were not different between the cirrhosis and non-cirrhosis groups (p=0.105 and p=0.224, respectively). Bleeding was more common in cirrhotic patients (p=0.054), and all cases were successfully controlled endoscopically. The median procedure and hospitalization duration did not differ between the groups. Overall survival was lower in cirrhotic patients (p=0.003), while disease-specific survival did not differ between the groups (p=0.85).

Conclusion: ESD could be a safe and effective treatment option for SENs in patients with cirrhosis. Detailed preprocedural assessments are needed, including determination of liver function, esophageal varix status, and remaining life expectancy, to identify patients who will obtain the greatest benefit.
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http://dx.doi.org/10.5946/ce.2021.242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178137PMC
May 2022

Prognostic Values of Inflammation-Based Scores and Fibrosis Markers in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization.

Diagnostics (Basel) 2022 May 7;12(5). Epub 2022 May 7.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.

Background: Inflammation is a key feature shaping the microenvironment of hepatocellular carcinoma (HCC), and liver fibrosis is associated with the prognosis of patients with HCC. In this study, we investigated whether baseline inflammation-based scores and serum fibrosis markers can help in predicting the prognosis of HCC patients treated with transarterial chemoembolization (TACE).

Methods: A total of 605 consecutive patients with HCC treated by TACE were included. The systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), FIB-4 index, and aspartate aminotransferase-to-platelet ratio index (APRI) were analyzed regarding their associations with disease progression and survival.

Results: All tested inflammation-based scores and fibrosis markers were significantly associated with tumor progression and overall survival in the univariate analyses. In the multivariate analysis, NLR (hazard ratio [HR], 1.06; = 0.007) and FIB-4 (HR = 1.02, = 0.008) were independent risk factors for disease progression, along with α-fetoprotein (AFP) levels, maximum tumor size and number, and presence of vascular invasion. Furthermore, NLR (HR, 1.09; < 0.001) and FIB-4 (HR, 1.02; = 0.02) were independent prognostic factors for survival.

Conclusions: High baseline NLR and FIB-4 levels might help the prediction of disease progression and death in patients with HCC after TACE.
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http://dx.doi.org/10.3390/diagnostics12051170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139803PMC
May 2022

Nanoelectrokinetic-assisted lateral flow assay for COVID-19 antibody test.

Biosens Bioelectron 2022 Sep 17;212:114385. Epub 2022 May 17.

Department of Electrical Engineering, Kwangwoon University, Seoul, 01897, Republic of Korea. Electronic address:

A lateral flow assay (LFA) platform is a powerful tool for point-of-care testing (POCT), especially for self-testing. Although the LFA platform provides a simple and disposable tool for Coronavirus disease of 2019 (COVID-19) antigen (Ag) and antibody (Ab) screening tests, the lower sensitivity for low virus titers has been a bottleneck for practical applications. Herein, we report the combination of a microfluidic paper-based nanoelectrokinetic (NEK) preconcentrator and an LFA platform for enhancing the sensitivity and limit of detection (LOD). Biomarkers were electrokinetically preconcentrated onto a specific layer using the NEK preconcentrator, which was then coupled with LFA diagnostic devices for enhanced performance. Using this nanoelectrokinetic-assisted LFA (NEK-LFA) platform for self-testing, the severe acute respiratory syndrome coronavirus 2 Immunoglobulin G (SARS-CoV-2 IgG) sample was preconcentrated from serum samples. After preconcentration, the LOD of the LFA was enhanced by 32-fold, with an increase in analytical sensitivity (16.4%), which may offer a new opportunity for POCT and self-testing, especially in the COVID-19 pandemic and endemic global context.
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http://dx.doi.org/10.1016/j.bios.2022.114385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112610PMC
September 2022

Clinical Significance of Epstein-Barr Virus and Infection in Gastric Carcinoma.

Gut Liver 2022 May 25. Epub 2022 May 25.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background/aims: Epstein-Barr virus (EBV) and (HP) coinfection may synergistically induce severe inflammatory responses in the stomach tissue, increasing the risk of developing gastric cancer. We aimed to analyze the effect of EBV and HP coinfection on the clinicopathologic features and prognosis of gastric cancer, as well as to evaluate the role of EBV infection in non-gastric carcinoma with lymphoid stroma (non-GCLS).

Methods: Overall, 956 patients who underwent surgery for gastric cancer between September 2014 and August 2015 were eligible and divided into groups, according to GCLS morphology, EBV infection, and HP infection. Clinicopathologic characteristics and oncologic outcomes were analyzed retrospectively.

Results: EBV and HP coinfection was significantly associated with male sex, proximal location, GCLS morphology, and equivocal p53 expression (p<0.001). Multivariate analysis revealed that EBV infection alone (hazard ratio [HR], 0.362; 95% CI, 0.131 to 0.996; p=0.049) and lower third location (HR, 0.624; 95% CI, 0.413 to 0.943; p=0.025) were inversely correlated with overall survival. During median follow-up period of 72 months, overall survival rate was not significantly different between the EBV and HP coinfection group and others (97.6% vs 86.8%; log-rank p=0.144). In non-GCLS patients (n=920), overall survival rate was not significantly different between the EBV infection group and others (96.9% vs 86.4%; log-rank p=0.126).

Conclusions: EBV and HP coinfection is not an independent prognostic factor for gastric cancer. EBV infection status, regardless of HP infection, affects the clinicopathologic features of all types of gastric cancer. However, it does not lead to a significant difference in overall survival of non-GCLS patients.
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http://dx.doi.org/10.5009/gnl210593DOI Listing
May 2022

Reevaluation of the expanded indications in undifferentiated early gastric cancer for endoscopic submucosal dissection.

World J Gastroenterol 2022 Apr;28(15):1548-1562

-Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea.

Background: Although the criteria for the indication of endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD-EGC) have been recently proposed, accumulating reports on the non-negligible rate of lymph node metastasis (LNM) after indicated ESD raise questions on the reliability of the current criteria.

Aim: To investigate the prevalence and risk factors of LNM in UD-EGC cases meeting the expanded indication for ESD.

Methods: We retrospectively reviewed 4780 UD-EGC cases that underwent surgical resection between January 2008 and February 2019 at Asan Medical Center, a tertiary university hospital in Korea. To identify the risk factors of LNM of UD-EGC meeting the expanded criteria for ESD, we performed a case-control study by matching the cases with LNM to those without at a ratio of 1:4. We reviewed the clinical, endoscopic, and histologic features of the cases to identify features with a significant difference according to the presence of LNM. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios (ORs).

Results: Of the 4780 UD-EGC cases, 1240 (25.9%) were identified to meet the expanded indication for ESD. Of the 1240 cases, 14 (1.1%) cases had LNM. Among the various clinical, endoscopic, and histopathological features that were evaluated, mixed histology (tumors consisting of 10%-90% of signet ring cells) had a marginally significant association ( 0.059) with the risk of LNM. Moreover, diffuse blurring of the muscularis mucosae (MM) underneath the tumorous epithelium, a previously unrecognized histologic feature, had a significant association with the absence of LNM ( = 0.028). Multivariate logistic regression analysis showed that the blurring of MM was the only explanatory variable significantly associated with a reduced risk of LNM (OR: 0.12, 95%CI: 0.02-0.95; = 0.045).

Conclusion: The risk of LNM is higher than expected when using the current expanded indication for UD-EGC. Histological evaluation could provide useful clues for reducing the risk of LNM.
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http://dx.doi.org/10.3748/wjg.v28.i15.1548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9048457PMC
April 2022

Association of Chronic Hepatitis B Infection and Antiviral Treatment With the Development of the Extrahepatic Malignancies: A Nationwide Cohort Study.

J Clin Oncol 2022 May 13:JCO2101285. Epub 2022 May 13.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

Purpose: Epidemiologic studies suggest that chronic hepatitis B (CHB) is a risk factor for various primary extrahepatic malignancies. Our aim was to evaluate the associations of CHB and nucleos(t)ide analog (NA) treatment with the risk of the development of extrahepatic malignancies.

Patients And Methods: We conducted an 18-month landmark analysis using nationwide claims data from the National Health Insurance Service of South Korea. Patients newly diagnosed with CHB in 2012-2014 (n = 90,944) and matched-controls (n = 685,436) were included. Patients with CHB were further classified as the NA-treated (CHB+/NA+, n = 6,539) or the NA-untreated (CHB+/NA-, n = 84,405) group. Inverse probability of treatment weighting analysis was applied to balance the treatment groups. Time-varying Cox analysis was performed to evaluate time-varying effect of NA treatment. The primary outcome was the development of any primary extrahepatic malignancy. Development of intrahepatic malignancy and death were considered as competing events.

Results: During the study period (median = 47.4 months), 30,413 patients (3.9%) developed any extrahepatic malignancy. The CHB+/NA- group had a higher overall risk of extrahepatic malignancy than the CHB+/NA+ group (adjusted subdistribution hazard ratio [aSHR] = 1.28; 95% CI, 1.12 to 1.45; < .001) or controls (aSHR = 1.22; 95% CI, 1.18 to 1.26; < .001). There was no difference in the risk of extrahepatic malignancy between the CHB+/NA+ group and the controls (CHB+/NA+ control: aSHR = 0.96; 95% CI, 0.84 to 1.08; = .48). In time-varying Cox analysis, the CHB+/NA- patients were associated with a higher risk of extrahepatic malignancy than the CHB+/NA+ patients (aSHR = 1.37; 95% CI, 1.23 to 1.52; < .001).

Conclusion: Patients with CHB have an elevated risk of developing primary extrahepatic malignancy. Long-term NA treatment was associated with a lower risk of extrahepatic malignancy development among patients with CHB.
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http://dx.doi.org/10.1200/JCO.21.01285DOI Listing
May 2022

Rapid and low-cost, and disposable electrical sensor using an extended gate field-effect transistor for cardiac troponin I detection.

Biomed Eng Lett 2022 May 8;12(2):197-203. Epub 2022 Feb 8.

Department of Electonic Engineering, Catholic Kwandong University, 24, Beomil-ro 579beon gil, Gangneung-si, Gangwond-do 25601 South Korea.

Field effect transistor (FET) biosensor is based on metal oxide field effect transistor that is gated by changes in the surface charges induced the reaction of biomolecules. In most cases of FET biosensor, FET biosensor is not being reused after the reaction; therefore, it is an important concept of investigate the biosensor with simplicity, cheap and reusability. However, the conventional cardiac troponin I (cTnI) sensing technique is inadequate owing to its low sensitivity and high operational time and cost. In this study, we developed a rapid and low-cost, and disposable electrical sensor using an extended gate field-effect transistor (EGFET) to detect cTnI, as a key biomarker for myocardiac infarction. We first investigated pH sensing characteristics according to the pH level, which provided a logarithmically linear sensitivity in the pH sensing buffer solution of approximately 57.9 mV/pH. Subsequently, we prepared a cTnI sample and monitored the reaction between cTnI and cTnI antibodies through the changes in the drain current and transfer curves. Our results showed that the EGFET biosensor could successfully detect the cTnI levels as well as the pH with low-cost and rapid detection.
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http://dx.doi.org/10.1007/s13534-022-00219-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046487PMC
May 2022

Prognostic Role of Circulating Tumor Cells in the Pulmonary Vein, Peripheral Blood, and Bone Marrow in Resectable Non-Small Cell Lung Cancer.

J Chest Surg 2022 Jun;55(3):214-224

Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam, Korea.

Background: Studies of the prognostic role of circulating tumor cells (CTCs) in early-stage non-small cell lung cancer (NSCLC) are still limited. This study investigated the prognostic power of CTCs from the pulmonary vein (PV), peripheral blood (PB), and bone marrow (BM) for postoperative recurrence in patients who underwent curative resection for NSCLC.

Methods: Forty patients who underwent curative resection for NSCLC were enrolled. Before resection, 10-mL samples were obtained of PB from the radial artery, blood from the PV of the lobe containing the tumor, and BM aspirates from the rib. A microfabricated filter was used for CTC enrichment, and immunofluorescence staining was used to identify CTCs.

Results: The pathologic stage was stage I in 8 patients (20%), II in 15 (38%), III in 14 (35%), and IV in 3 (8%). The median number of PB-, PV-, and BM-CTCs was 4, 4, and 5, respectively. A time-dependent receiver operating characteristic curve analysis showed that PB-CTCs had excellent predictive value for recurrence-free survival (RFS), with the highest area under the curve at each time point (first, second, and third quartiles of RFS). In a multivariate Cox proportional hazard regression model, PB-CTCs were an independent risk factor for recurrence (hazard ratio, 10.580; 95% confidence interval, 1.637-68.388; p<0.013).

Conclusion: The presence of ≥4 PB-CTCs was an independent poor prognostic factor for RFS, and PV-CTCs and PB-CTCs had a positive linear correlation in patients with recurrence.
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http://dx.doi.org/10.5090/jcs.21.140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178304PMC
June 2022

Surface Functionalization of Enzyme-Coronated Gold Nanoparticles with an Erythrocyte Membrane for Highly Selective Glucose Assays.

Anal Chem 2022 05 19;94(17):6473-6481. Epub 2022 Apr 19.

School of Biomedical Engineering, Korea University, Seoul 02841, South Korea.

Colorimetric glucose sensors using enzyme-coronated gold nanoparticles have been developed for high-throughput assays to monitor the blood glucose levels of diabetic patients. Although those sensors have shown sensitivity and wide linear detection ranges, they suffer from poor selectivity and stability in detecting blood glucose, which has limited their practical use. To address this limitation, herein, we functionalized glucose-oxidase-coronated gold nanoparticles with an erythrocyte membrane (EM-GOx-GNPs). Because the erythrocyte membrane (EM) selectively facilitates the permeation of glucose via glucose transporter-1 (GLUT1), the functionalization of GOx-GNPs with EM improved the stability, selectivity (3.3- to 15.8-fold higher), and limit of detection (LOD). Both membrane proteins, GLUT1 and aquaporin-1 (AQP1), on EM were shown to be key components for selective glucose detection by treatment with their inhibitors. Moreover, we demonstrated the stability of EM-GOx-GNPs in high-antioxidant-concentration conditions, under long-term storage (∼4 weeks) and a freeze-thaw cycle. Selectivity of the EM-GOx-GNPs against other saccharides was increased, which improved the LOD in phosphate-buffered saline and human serum. Our results indicated that the functionalization of colorimetric glucose sensors with EM is beneficial for improving selectivity and stability, which may make them candidates for use in a practical glucose sensor.
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http://dx.doi.org/10.1021/acs.analchem.1c04541DOI Listing
May 2022

Improving the Performance of Radiologists Using Artificial Intelligence-Based Detection Support Software for Mammography: A Multi-Reader Study.

Korean J Radiol 2022 05 4;23(5):505-516. Epub 2022 Apr 4.

Department of Radiology, Gyeongsang National University Hospital and College of Medicine, Gyeongsang National University, Jinju, Korea.

Objective: To evaluate whether artificial intelligence (AI) for detecting breast cancer on mammography can improve the performance and time efficiency of radiologists reading mammograms.

Materials And Methods: A commercial deep learning-based software for mammography was validated using external data collected from 200 patients, 100 each with and without breast cancer (40 with benign lesions and 60 without lesions) from one hospital. Ten readers, including five breast specialist radiologists (BSRs) and five general radiologists (GRs), assessed all mammography images using a seven-point scale to rate the likelihood of malignancy in two sessions, with and without the aid of the AI-based software, and the reading time was automatically recorded using a web-based reporting system. Two reading sessions were conducted with a two-month washout period in between. Differences in the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and reading time between reading with and without AI were analyzed, accounting for data clustering by readers when indicated.

Results: The AUROC of the AI alone, BSR (average across five readers), and GR (average across five readers) groups was 0.915 (95% confidence interval, 0.876-0.954), 0.813 (0.756-0.870), and 0.684 (0.616-0.752), respectively. With AI assistance, the AUROC significantly increased to 0.884 (0.840-0.928) and 0.833 (0.779-0.887) in the BSR and GR groups, respectively ( = 0.007 and < 0.001, respectively). Sensitivity was improved by AI assistance in both groups (74.6% vs. 88.6% in BSR, < 0.001; 52.1% vs. 79.4% in GR, < 0.001), but the specificity did not differ significantly (66.6% vs. 66.4% in BSR, = 0.238; 70.8% vs. 70.0% in GR, = 0.689). The average reading time pooled across readers was significantly decreased by AI assistance for BSRs (82.73 vs. 73.04 seconds, < 0.001) but increased in GRs (35.44 vs. 42.52 seconds, < 0.001).

Conclusion: AI-based software improved the performance of radiologists regardless of their experience and affected the reading time.
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http://dx.doi.org/10.3348/kjr.2021.0476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081685PMC
May 2022

Endoscopic scoring system for gastric atrophy and intestinal metaplasia: correlation with OLGA and OLGIM staging: a single-center prospective pilot study in Korea.

Scand J Gastroenterol 2022 Apr 6:1-8. Epub 2022 Apr 6.

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background/aims: We aimed to develop an endoscopic scoring system to evaluate gastric atrophy and intestinal metaplasia using narrow-band imaging (NBI) and near focus mode (NFM) to compare endoscopic scores with the Operative link for gastritis assessment (OLGA) and the Operative link for gastric intestinal metaplasia assessment (OLGIM).

Methods: A total of 51 patients who underwent diagnostic esophagogastroduodenoscopy were prospectively enrolled and endoscopic scoring using NBI and NFM was performed. Four areas (the lesser and greater curvatures of the antrum and the lesser and greater curvature side of the corpus) were observed and biopsies were taken. The degree of atrophy was scored from 0 to 2 according to the Kimura-Takemoto classification. The degree of intestinal metaplasia was scored from 0 to 4 according to the location and the extent of the intestinal metaplasia.

Results: The correlation coefficient for atrophy between the endoscopic and histologic scores was 0.70 (95% CI: 0.52-0.81  < .001) and for intestinal metaplasia, it was 0.75 (95% CI: 0.60-0.85;  < .001). For atrophic gastritis, an endoscopic score >1 correlated with OLGA stage III and IV with a sensitivity, specificity, positive predictive value, negative predictive value, and agreement of 88, 74, 75, 87, and 80.4%, respectively, and for intestinal metaplasia, an endoscopic score >1 correlated with high OLGIM stage III and IV with 100, 59, 69, 100, and 78.4%, respectively.

Conclusions: Endoscopic scoring for gastric atrophy and intestinal metaplasia using NBI-NFM likely correlates with histologic staging in Korea, a high-risk region for gastric cancer.
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http://dx.doi.org/10.1080/00365521.2022.2055974DOI Listing
April 2022

Comparison of the outcomes between sorafenib and lenvatinib as the first-line systemic treatment for HBV-associated hepatocellular carcinoma: a propensity score matching analysis.

BMC Gastroenterol 2022 Mar 25;22(1):135. Epub 2022 Mar 25.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

Background/aim: In a randomized controlled trial, lenvatinib was non-inferior to sorafenib in overall survival (OS) of patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to compare the effects of sorafenib and lenvatinib as first-line systemic therapy against uHCC with real-world data in chronic hepatitis B patients.

Methods: This retrospective single-center study involved 132 patients with HBV-related uHCC. Propensity score matching (PSM) was used to balance the baseline characteristics, including age, sex, serum alpha-fetoprotein levels, Child-Pugh class, tumor size, and tumor stage. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), time to progression (TTP), and tumor response.

Results: After PSM, the final analysis included 44 patients treated with lenvatinib and 88 with sorafenib. The OS (7.0 vs 9.2 months, p = 0.070) and PFS (4.6 vs 2.4 months, p = 0.134) were comparable between the two drugs. Multivariable analysis showed that lenvatinib and sorafenib were not independent prognostic factors of OS (adjusted hazard ratio = 1.41, 95% confidence interval = 0.96-2.08, p = 0.077) after adjustment for baseline alpha-fetoprotein levels, total bilirubin levels, alanine aminotransferase level, performance status, tumor stage, and tumor size. However, the lenvatinib group had a significantly prolonged TTP (5.2 vs 2.5 months, p = 0.018) and a higher objective response rate (18.2% vs 4.5%, p = 0.020) and disease control rate (77.3% vs 47.7%, p = 0.001) than the sorafenib group.

Conclusions: Our study demonstrated that lenvatinib had a comparable OS and PFS but longer TTP and better tumor response compared to sorafenib in patients with HBV-related uHCC.
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http://dx.doi.org/10.1186/s12876-022-02210-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951695PMC
March 2022

Green Synthesis of Laser-Induced Graphene with Copper Oxide Nanoparticles for Deicing Based on Photo-Electrothermal Effect.

Nanomaterials (Basel) 2022 Mar 14;12(6). Epub 2022 Mar 14.

Department of Optics and Mechatronics Engineering, Pusan National University, Pusan 46241, Korea.

Homogenously dispersed Cu oxide nanoparticles on laser-induced graphene (LIG) were fabricated using a simple two-step laser irradiation. This work emphasized the synergetic photo-electrothermal effect in Cu oxide particles embedded in LIG. Our flexible hybrid composites exhibited high mechanical durability and excellent thermal properties. Moreover, the Cu oxide nanoparticles in the carbon matrix of LIG enhanced the light trapping and multiple electron internal scattering for the electrothermal effect. The best conditions for deicing devices were also studied by controlling the amount of Cu solution. The deicing performance of the sample was demonstrated, and the results indicate that the developed method could be a promising strategy for maintaining lightness, efficiency, excellent thermal performance, and eco-friendly 3D processing capabilities.
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http://dx.doi.org/10.3390/nano12060960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951176PMC
March 2022

Aspirin use and risk of hepatocellular carcinoma in patients with chronic hepatitis B with or without cirrhosis.

Hepatology 2022 Aug 17;76(2):492-501. Epub 2022 Mar 17.

Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background And Aims: Studies on differential effect of aspirin therapy on HCC risk across the spectrum of liver diseases are lacking. We investigated the association between aspirin use and risks of HCC, liver-associated death, and major bleeding in chronic hepatitis B (CHB) patients with or without cirrhosis.

Approach And Results: We identified 329,635 eligible adults with CHB from 2007 through 2017, using the Korean National Health Insurance Service database, including patients who received aspirin for ≥90 consecutive days (n = 20,200) and patients who never received antiplatelet therapy (n = 309,435). Risks of HCC, liver-associated mortality, and major bleeding were estimated in a propensity-score-matched cohort (19,003 pairs), accounting for competing risks. With a median follow-up of 6.7 years, 10-year cumulative incidence of HCC was 9.5% in the aspirin-treated group and 11.3% in the untreated group (adjusted subdistribution hazard ratio [aSHR], 0.85; 95% CI, 0.78-0.92). However, among patients with cirrhosis (2479 pairs), an association of aspirin use with HCC risk was not evident (aSHR, 1.00; 95% CI, 0.85-1.18). Cirrhosis status had a significant effect on the association between aspirin use and HCC risk (p , n = 0.04). Aspirin use was also associated with lower liver-associated mortality (aSHR, 0.80; 95% CI, 0.71-0.90). Moreover, aspirin use was not associated with major bleeding risk (aSHR, 1.09; 95% CI, 0.99-1.21).

Conclusions: Aspirin use was associated with reduced risks of HCC and liver-associated mortality in adults with CHB. Cirrhosis status had a substantial effect on the association between aspirin use and HCC risk.
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http://dx.doi.org/10.1002/hep.32380DOI Listing
August 2022

Effectiveness of Lenvatinib Versus Sorafenib for Unresectable Hepatocellular Carcinoma in Patients with Hepatic Decompensation.

Dig Dis Sci 2022 Jan 20. Epub 2022 Jan 20.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

Background/aim: Lenvatinib and sorafenib are currently available to treat patients with advanced hepatocellular carcinoma (HCC). However, since the clinical trials evaluating the efficacy of lenvatinib and sorafenib included only patients with Child-Pugh class A, little is known about the effectiveness of the treatments in patients with hepatic decompensation. We compared the effectiveness of lenvatinib and sorafenib in decompensated patients with unresectable HCC.

Methods: Consecutive patients who were classified as Child-Pugh class B or C and received lenvatinib or sorafenib as first-line systemic therapy for unresectable HCC between November 2018 and April 2020 at a tertiary referral center were included in this retrospective study. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), time-to-progression, best overall tumor response, and safety profiles.

Results: Among 94 patients, 34 received lenvatinib and 60 received sorafenib. The median OS was 4.1 months (95% confidence interval [CI], 2.9-5.2): 4.2 months (95% CI, 2.9-5.3) for lenvatinib and 4.1 months (95% CI, 2.7-6.4) for sorafenib. The treatment regimen was not associated with significant improvement in OS after adjusting for covariables (adjusted hazard ratio [aHR], 0.92; 95% CI, 0.54-1.54; P = 0.74). The treatment regimen was not an independent predictor of PFS (lenvatinib vs. sorafenib; aHR, 0.77; 95% CI, 0.48-1.24; P = 0.28). HRs were maintained even after balancing with the inverse probability treatment weighting method. Objective response rates were 11.8% and 6.7% in patients receiving lenvatinib and sorafenib, respectively (P = 0.45). Ten patients in both groups (five in the lenvatinib group and five in the sorafenib group) underwent dose modification due to adverse events, and significant difference was not observed between the treatment groups (P = 0.49).

Conclusion: The effectiveness of lenvatinib and sorafenib was comparable for the treatment of unresectable HCC in decompensated patients.
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http://dx.doi.org/10.1007/s10620-021-07365-9DOI Listing
January 2022

Outcome of Initial Progression During Nivolumab Treatment for Hepatocellular Carcinoma: Should We Use iRECIST?

Front Med (Lausanne) 2021 13;8:771887. Epub 2021 Dec 13.

Center for Liver and Pancreato-Biliary Cancer, National Cancer Center, Goyang, South Korea.

Immune response evaluation criteria in solid tumors (iRECIST) is recommended during immune checkpoint inhibitors (ICIs) treatment, due to the possibility of pseudoprogression. We evaluated the frequency of pseudoprogression in hepatocellular carcinoma (HCC) patients. This retrospective multicenter study involved 158 consecutive patients who underwent nivolumab treatment for HCC in Korea. At the initial evaluation, 94 patients presented with immune unconfirmed progressive disease, and 22 continued nivolumab. At the second evaluation, 21 of the 22 patients (95.5%) had confirmed progression and no pseudoprogression was observed. Considering low possibility of pseudoprogression, iRECIST may not be required for HCC.
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http://dx.doi.org/10.3389/fmed.2021.771887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710731PMC
December 2021

Cost-Effectiveness of Adjuvant Immunotherapy With Cytokine-Induced Killer Cell for Hepatocellular Carcinoma Based on a Randomized Controlled Trial and Real-World Data.

Front Oncol 2021 3;11:728740. Epub 2021 Dec 3.

College of Pharmacy, Sahmyook University, Seoul, South Korea.

Background: Studies using data from randomized controlled trials (RCTs) and real-world data (RWD) have suggested that adjuvant cytokine-induced killer (CIK) cell immunotherapy after curative treatment for hepatocellular carcinoma (HCC) prolongs recurrence-free survival (RFS) and overall survival (OS). However, the cost-effectiveness of CIK cell immunotherapy as an adjuvant therapy for HCC compared to no adjuvant therapy is uncertain.

Methods: We constructed a partitioned survival model to compare the expected costs, life-year (LY), and quality-adjusted life-year (QALY) of a hypothetical population of 10,000 patients between CIK cell immunotherapy and no adjuvant therapy groups. Patients with HCC aged 55 years who underwent a potentially curative treatment were simulated with the model over a 20-year time horizon, from a healthcare system perspective. To model the effectiveness, we used OS and RFS data from RCTs and RWD. We estimated the incremental cost-effectiveness ratios (ICERs) and performed extensive sensitivity analyses.

Results: Based on the RCT data, the CIK cell immunotherapy incrementally incurred a cost of $61,813, 2.07 LYs, and 1.87 QALYs per patient compared to no adjuvant therapy, and the estimated ICER was $33,077/QALY. Being less than the willingness-to-pay threshold of $50,000/QALY, CIK cell immunotherapy was cost-effective. Using the RWD, the ICER was estimated as $25,107/QALY, which is lower than that obtained using RCT. The time horizon and cost of productivity loss were the most influential factors on the ICER.

Conclusion: We showed that receiving adjuvant CIK cell immunotherapy was more cost-effective than no adjuvant therapy in patients with HCC who underwent a potentially curative treatment, attributed to prolonged survival, reduced recurrence of HCC, and better prognosis of recurrence. Receiving CIK cell immunotherapy may be more cost-effective in real-world clinical practice.
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http://dx.doi.org/10.3389/fonc.2021.728740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8682810PMC
December 2021

TM4SF5-mediated liver malignancy involves NK cell exhaustion-like phenotypes.

Cell Mol Life Sci 2021 Dec 18;79(1):49. Epub 2021 Dec 18.

Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.

Aberrant extracellular matrix and immune cell alterations within the tumor microenvironment promote the pathological progression of liver carcinogenesis. Although transmembrane 4 L six family member 5 (TM4SF5) is involved in liver fibrosis and cancer, its mechanism avoiding immune surveillance during carcinogenesis remains unknown. We investigated how TM4SF5-mediated signaling caused immune evasion using in vitro primary cells and in vivo liver tissues from genetic or chemically induced mouse models. TM4SF5-transgenic and diethylnitrosamine (DEN)-induced liver cancer mouse models exhibited fibrotic and cancerous livers, respectively, with enhanced TM4SF5, pYSTAT3, collagen I, and laminin γ2 levels. These TM4SF5-mediated effects were abolished by TM4SF5 inhibitor, 4'-(p-toluenesulfonylamido)-4-hydroxychalcone (TSAHC). TM4SF5-dependent tumorigenesis involved natural killer (NK) cell exhaustion-like phenotypes including the reduction of NK cell number or function, which were blocked with TSAHC treatment. TM4SF5 expression in cancer cells downregulated stimulatory ligands and receptors for NK cell cytotoxicity, including SLAMF6, SLAMF7, MICA/B, and others. TM4SF5 suppression or inhibition reduced STAT3 signaling activity and recovered the receptor levels and NK cell surveillance, leading to reduced fibrotic and cancerous phenotypes, and longer survival. Altogether, these findings suggest that TM4SF5-mediated STAT3 activity for extracellular matrix modulation is involved in the progression of liver disease to HCC and that TM4SF5 appears to suppress NK cells during liver carcinogenesis.
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http://dx.doi.org/10.1007/s00018-021-04051-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739317PMC
December 2021

Yttrium-90 Radioembolization Is Associated with Better Clinical Outcomes in Patients with Hepatocellular Carcinoma Compared with Conventional Chemoembolization: A Propensity Score-Matched Study.

J Hepatocell Carcinoma 2021 7;8:1565-1577. Epub 2021 Dec 7.

Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.

Background: Both trans-arterial radioembolization (TARE) and conventional trans-arterial chemoembolization (TACE) can effectively control hepatocellular carcinoma (HCC) in patients who are not suitable for curative resection. This study compared the effectiveness of TARE and conventional TACE as the initial trans-arterial treatment for hepatocellular carcinoma (HCC) assessed by tumor response and clinical outcomes.

Material And Methods: Data were retrospectively analyzed the propensity score-matched cohort for overall survival (OS), progression-free survival (PFS), and intrahepatic PFS in patients who have received TARE or TACE as the first HCC treatment from March 2012 to December 2017.

Results: A total of 138 patients initially treated with TARE (n = 54) or TACE (n = 84) was included in this study. Of 138 patients, median age was 59 years and the mean follow-up period was 27.6 months. TARE showed better OS (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.31-0.92, log-rank = 0.02), better PFS (HR = 0.51, 95% CI = 0.36-0.97, log-rank = 0.04), and better intrahepatic PFS (HR = 0.51, 95% CI = 0.30-0.88, log-rank = 0.01) compared with TACE. TARE was an independent prognostic factor for OS (adjusted HR [aHR] = 0.52, 95% CI = 0.30-0.90, = 0.02), PFS (aHR = 0.57, 95% CI = 0.35-0.94, = 0.03), and intrahepatic PFS (aHR = 0.49, 95% CI = 0.28-0.84, = 0.01).

Conclusion: TARE as initial trans-arterial treatment is associated with better clinical outcomes such as longer OS compared with TACE in patients with HCC.
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http://dx.doi.org/10.2147/JHC.S335879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665867PMC
December 2021

Long-Term Outcomes of Transarterial Radioembolization for Large Single Hepatocellular Carcinoma: A Comparison to Resection.

J Nucl Med 2022 Aug 9;63(8):1215-1222. Epub 2021 Dec 9.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

The surgical treatment for large hepatocellular carcinoma (HCC) remains controversial because of a high risk of recurrence after resection. This study aimed to compare long-term outcomes of transarterial radioembolization (TARE) with resection for patients with large HCC. This retrospective cohort study included 557 patients who were initially treated with either resection ( = 500) or TARE ( = 57) for large (≥5 cm), single nodular HCC at 2 tertiary centers in Korea. Patients with major portal vein tumor thrombosis or extrahepatic metastasis were excluded. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), time to intrahepatic progression (TTIP), and safety. The resection group was younger (median, 60 vs. 69 y) and had a smaller tumor size (median, 7.0 vs. 10.0 cm) (all < 0.05). After baseline characteristics were balanced using inverse-probability-of-treatment weighting, the OS (hazard ratio [HR], 0.98; 95% CI, 0.40-2.43; = 0.97), TTP (HR, 1.10; 95% CI, 0.55-2.20; = 0.80), and TTIP (HR, 1.45; 95% CI, 0.72-2.93; = 0.30) of the TARE group was comparable to the resection group. TARE was not an independent risk for OS (adjusted HR, 1.04; 95% CI, 0.42-2.59; = 0.93), TTP (adjusted HR, 0.98; 95% CI, 0.50-1.95; = 0.96), or TTIP (adjusted HR, 1.30; 95% CI, 0.65-2.58; = 0.46). The TARE group had a shorter hospital stay and fewer adverse events than the resection group. Compared with surgical resection for large single nodular HCC, TARE showed a comparable OS, TTP, and TTIP and a better safety profile.
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http://dx.doi.org/10.2967/jnumed.121.263147DOI Listing
August 2022

Comparison of Overall Survival between Surgical Resection and Radiofrequency Ablation for Hepatitis B-Related Hepatocellular Carcinoma.

Cancers (Basel) 2021 Nov 29;13(23). Epub 2021 Nov 29.

Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea.

It remains controversial whether surgical resection, compared to radiofrequency ablation (RFA), improves overall survival (OS) in patients with early hepatocellular carcinoma (HCC). This study aimed to compare OS after RFA with that after resection for HCC. This retrospective study included patients who underwent RFA or surgical resection as initial treatment for hepatitis B virus (HBV)-related HCC at a very early or early stage. A total of 761 patients (RFA, = 194; resection, = 567) from Seoul National University Hospital (Seoul, South Korea) and 1277 patients (RFA, = 352; resection, = 925) from the Korean Primary Liver Cancer Registry were included in the hospital and nationwide cohorts, respectively. Primary and secondary endpoints were OS and recurrence-free survival (RFS), respectively. Additional analysis was performed when the history of the antiviral treatment and the type of prescribed nucleos(t)ide analogue were confirmed. The rate of complications was compared between the two treatment groups in the hospital cohort. Baseline characteristics were balanced, using inverse probability of treatment weighting (IPTW). In the hospital cohort, the RFA group had a smaller mean tumor size (1.7 vs. 3.9 cm) but a higher proportion of cirrhotic patients than the resection group (85.6% vs. 63.1%) (both < 0.01). During 81.0 (interquartile range, 62.3-107.1) months of follow-up, there was no difference in OS (adjusted hazard ratio (aHR) = 0.870, 95% confidence interval (CI) = 0.400-1.897, = 0.73) and RFA was associated with shorter RFS (aHR = 1.562, 95% CI = 1.099-2.219, = 0.01) after employing IPTW. Antiviral treatment was independently associated with longer OS (aHR = 0.444, 95% CI = 0.251-0.786, = 0.01) as well as RFS (aHR = 0.544, 95% CI = 0.391-0.757, < 0.01) in the hospital cohort. In the nationwide cohort, there was no difference in OS (aHR = 0.981, 95% CI = 0.661-1.456, = 0.92) between the two treatment groups when adjusted for antiviral treatment, which was a negative independent risk factor for mortality (aHR = 0.655, 95% CI = 0.451-0.952, = 0.03) after IPTW. Among patients treated with tenofovir (n = 96) or entecavir (n = 184) in the hospital cohort, there was no difference in either OS (aHR = 0.522, 95% CI = 0.058-4.724, = 0.56) or RFS (aHR = 1.116, 95% CI = 0.738-1.688, = 0.60). The overall incidence of complications was higher in the resection group (26.3%) than in the RFA group (13.9%) ( < 0.01). RFA may provide comparable OS to resection in the treatment of very early or early HCC with a lower rate of complications, although RFS is marginally shorter than in the resection group after adjusting for antiviral treatment. Regardless of the type of NA, antiviral treatment in patients with HBV-related HCC is strongly associated with both OS and RFS.
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http://dx.doi.org/10.3390/cancers13236009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657180PMC
November 2021

Efficacy of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide in treatment-naive hepatitis B patients.

Hepatol Int 2021 Dec 20;15(6):1328-1336. Epub 2021 Nov 20.

Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Background And Aims: Antiviral agents for chronic hepatitis B (CHB) reduced the risk of hepatocellular carcinoma (HCC) development. The outcomes of entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) were compared in patients with CHB.

Methods: Between 2017 and 2019, treatment-naïve patients with CHB treated with ETV, TDF, and TAF were recruited from three Korean tertiary institutes. The cumulative incidences of HCC and orthotopic liver transplantation (OLT) or mortality were calculated and compared using Kaplan-Meier analysis before and after trimatch.

Results: Among recruited 2082 patients, 43 patients developed HCC, whereas 66 developed OLT or mortality. Before trimatch, the cumulative incidence of HCC was statistically similar among patients treated with three antiviral agents (p = 0.340). However, the cumulative probability of OLT or mortality development in patients treated with ETV or TDF was significantly higher than that of patients with TAF before trimatch (all p < 0.05). On multivariate analysis, male sex [hazard ratio (HR) 2.990] and older age (HR 1.044) were independently associated with an increased risk of HCC development, whereas higher platelet count (HR 0.993) was independently associated with a decreased risk (all p < 0.05). The type of antiviral agents did not significantly influence the risk of HCC and OLT or mortality development (all p > 0.05). After trimatch, no significant difference in the cumulative probability for HCC and OLT or mortality according to antiviral agents was found (all p > 0.05).

Conclusions: The outcomes of ETV, TDF, and TAF on the risk of HCC and OLT or mortality were statistically similar in treatment-naïve patients with CHB.
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http://dx.doi.org/10.1007/s12072-021-10262-yDOI Listing
December 2021

GLRX3, a novel cancer stem cell-related secretory biomarker of pancreatic ductal adenocarcinoma.

BMC Cancer 2021 Nov 18;21(1):1241. Epub 2021 Nov 18.

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.

Background: Cancer stem cells (CSCs) are implicated in carcinogenesis, cancer progression, and recurrence. Several biomarkers have been described for pancreatic ductal adenocarcinoma (PDAC) CSCs; however, their function and mechanism remain unclear.

Method: In this study, secretome analysis was performed in pancreatic CSC-enriched spheres and control adherent cells for biomarker discovery. Glutaredoxin3 (GLRX3), a novel candidate upregulated in spheres, was evaluated for its function and clinical implication.

Results: PDAC CSC populations, cell lines, patient tissues, and blood samples demonstrated GLRX3 overexpression. In contrast, GLRX3 silencing decreased the in vitro proliferation, migration, clonogenicity, and sphere formation of cells. GLRX3 knockdown also reduced tumor formation and growth in vivo. GLRX3 was found to regulate Met/PI3K/AKT signaling and stemness-related molecules. ELISA results indicated GLRX3 overexpression in the serum of patients with PDAC compared to that in healthy controls. The sensitivity and specificity of GLRX3 for PDAC diagnosis were 80.0 and 100%, respectively. When GLRX3 and CA19-9 were combined, sensitivity was significantly increased to 98.3% compared to that with GLRX3 or CA19-9 alone. High GLRX3 expression was also associated with poor disease-free survival in patients receiving curative surgery.

Conclusion: Overall, these results indicate GLRX3 as a novel diagnostic marker and therapeutic target for PDAC targeting CSCs.
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http://dx.doi.org/10.1186/s12885-021-08898-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8603516PMC
November 2021
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