1.Major clinical research advances in gynecologic cancer in 2023:a tumultuous year for endometrial cancer
Seung-Hyuk SHIM ; Jung-Yun LEE ; Yoo-Young LEE ; Jeong-Yeol PARK ; Yong Jae LEE ; Se Ik KIM ; Gwan Hee HAN ; Eun Jung YANG ; Joseph J NOH ; Ga Won YIM ; Joo-Hyuk SON ; Nam Kyeong KIM ; Tae-Hyun KIM ; Tae-Wook KONG ; Youn Jin CHOI ; Angela CHO ; Hyunji LIM ; Eun Bi JANG ; Hyun Woong CHO ; Dong Hoon SUH
Journal of Gynecologic Oncology 2024;35(2):e66-
In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.
2.Major clinical research advances in gynecologic cancer in 2023:a tumultuous year for endometrial cancer
Seung-Hyuk SHIM ; Jung-Yun LEE ; Yoo-Young LEE ; Jeong-Yeol PARK ; Yong Jae LEE ; Se Ik KIM ; Gwan Hee HAN ; Eun Jung YANG ; Joseph J NOH ; Ga Won YIM ; Joo-Hyuk SON ; Nam Kyeong KIM ; Tae-Hyun KIM ; Tae-Wook KONG ; Youn Jin CHOI ; Angela CHO ; Hyunji LIM ; Eun Bi JANG ; Hyun Woong CHO ; Dong Hoon SUH
Journal of Gynecologic Oncology 2024;35(2):e66-
In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.
3.Major clinical research advances in gynecologic cancer in 2023:a tumultuous year for endometrial cancer
Seung-Hyuk SHIM ; Jung-Yun LEE ; Yoo-Young LEE ; Jeong-Yeol PARK ; Yong Jae LEE ; Se Ik KIM ; Gwan Hee HAN ; Eun Jung YANG ; Joseph J NOH ; Ga Won YIM ; Joo-Hyuk SON ; Nam Kyeong KIM ; Tae-Hyun KIM ; Tae-Wook KONG ; Youn Jin CHOI ; Angela CHO ; Hyunji LIM ; Eun Bi JANG ; Hyun Woong CHO ; Dong Hoon SUH
Journal of Gynecologic Oncology 2024;35(2):e66-
In the 2023 series, we summarized the major clinical research advances in gynecologic oncology based on communications at the conference of Asian Society of Gynecologic Oncology Review Course. The review consisted of 1) Endometrial cancer: immune checkpoint inhibitor, antibody drug conjugates (ADCs), selective inhibitor of nuclear export, CDK4/6 inhibitors WEE1 inhibitor, poly (ADP-ribose) polymerase (PARP) inhibitors. 2) Cervical cancer: surgery in low-risk early-stage cervical cancer, therapy for locally advanced stage and advanced, metastatic, or recurrent setting; and 3) Ovarian cancer: immunotherapy, triplet therapies using immune checkpoint inhibitors along with antiangiogenic agents and PARP inhibitors, and ADCs. In 2023, the field of endometrial cancer treatment witnessed a landmark year, marked by several practice-changing outcomes with immune checkpoint inhibitors and the reliable efficacy of PARP inhibitors and ADCs.
4.Noninferiority Outcomes of Besifovir Compared to Tenofovir Alafenamide in Treatment-Naïve Patients with Chronic Hepatitis B
Tae Hyung KIM ; Ji Hoon KIM ; Hyung Joon YIM ; Yeon Seok SEO ; Sun Young YIM ; Young-Sun LEE ; Young Kul JUNG ; Jong Eun YEON ; Soon Ho UM ; Kwan Soo BYUN
Gut and Liver 2024;18(2):305-315
Background/Aims:
Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB).However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB.
Methods:
We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes.
Results:
A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (–0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15.
Conclusions
BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.
5.Impacts of muscle mass dynamics on prognosis of outpatients with cirrhosis
Tae Hyung KIM ; Young Kul JUNG ; Hyung Joon YIM ; Joo Won BAIK ; Sun Young YIM ; Young-Sun LEE ; Yeon Seok SEO ; Ji Hoon KIM ; Jong Eun YEON ; Kwan Soo BYUN
Clinical and Molecular Hepatology 2022;28(4):876-889
Background/Aims:
Sarcopenia negatively affects the prognosis of cirrhotic patients, but clinical implications of changes in muscle mass remain unclear. We aimed to elucidate its role in the prognosis of outpatients with cirrhosis.
Methods:
Patients with cirrhosis who underwent annual abdominal computed tomography (CT) for hepatocellular carcinoma surveillance were included in the prospective cohort. The L3 skeletal muscle index (SMI) was adopted as a proxy for the amount of skeletal muscle, and the rate of SMI change between inclusion and after 1 year (ΔSMI/yr%) was calculated.
Results:
In total, 595 patients underwent a second CT after 1 year. Among them, 109 and 64 patients had sarcopenia and Child-Pugh class B/C decompensation at inclusion, which changed to 103 and 45 at the 1-year follow-up, respectively. During a median follow-up of 30.1 months after 1 year, 86 patients had at least one cirrhosis complication, and 18 died or received liver transplantation. In the development of cirrhosis complications, ΔSMI/yr% was independently associated, even after adjusting for the Child-Pugh and model for end stage liver disease (MELD)-Na scores. In addition, ΔSMI/yr% showed a good predictive performance for the development of cirrhosis complications within 6 months after 1-year follow-up in all subgroups, with a cut-off of -2.62 (sensitivity, 83.9%; specificity, 74.5%) in the overall population. SMI at 1-year and Child-Pugh score were independent factors associated with survival. In addition, changes in sarcopenia status significantly stratified survival.
Conclusion
ΔSMI/yr% was a good predictor of the development of cirrhosis complications in outpatients with cirrhosis, independent of Child-Pugh and MELD scores.
6.Comparison of Sorafenib versus Hepatic Arterial Infusion Chemotherapy-Based Treatment for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis
Young Eun AHN ; Sang Jun SUH ; Hyung Joon YIM ; Yeon Seok SEO ; Eileen L. YOON ; Tae Hyung KIM ; Young Sun LEE ; Sun Young YIM ; Hae Rim KIM ; Seong Hee KANG ; Young Kul JUNG ; Ji Hoon KIM ; Jong Eun YEON ; Soon Ho UM ; Kwan Soo BYUN
Gut and Liver 2021;15(2):284-294
Background/Aims:
Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT.
Methods:
Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR).
Results:
Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030).
Conclusions
HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.
7.Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome
Han Ah LEE ; Jihwan LIM ; Hyung Joon JOO ; Young-Sun LEE ; Young Kul JUNG ; Ji Hoon KIM ; Hyunggin AN ; Hyung Joon YIM ; Yoon Tae JEEN ; Jong Eun YEON ; Do-Sun LIM ; Kwan Soo BYUN ; Yeon Seok SEO
Clinical and Molecular Hepatology 2021;27(3):463-473
Background/Aims:
Useful biomarkers for metabolic syndrome have been insufficient. We investigated the performance of serum milk fat globule-EGF factor-8 (MFG-E8), the key mediator of inflammatory pathway, in diagnosis of metabolic syndrome.
Methods:
Subjects aged between 30 and 64 years were prospectively enrolled in the Seoul Metabolic Syndrome cohort. Serum MFG-E8 levels were measured at baseline.
Results:
A total of 556 subjects were included, comprising 279 women (50.2%) and 277 men (49.8%). Metabolic syndrome was diagnosed in 236 subjects (42.4%), and the mean MFG-E8 level of subjects with metabolic syndrome was significantly higher than that of subjects without metabolic syndrome (P<0.001). MFG-E8 level was significantly correlated with all metabolic syndrome components and pulse wave velocity (all P<0.05). Subjects were categorized into two groups according to the best MFG-E8 cut-off value as follows: group 1, MFG-E8 level <4,745.1 pg/mL (n=401, 72.1%); and group 2, MFG-E8 level ≥4,745.1 (n=155, 27.9%). At baseline, metabolic syndrome in group 2 was significantly more prevalent than in group 1 (63.9% vs. 34.2%, P<0.001). During median follow-up of 17 months, metabolic syndrome developed in 122 (38.1%) subjects among 320 subjects without it at baseline. The incidence of metabolic syndrome in group 2 was significantly higher than that in group 1 (55.4% vs. 34.5%, P=0.003). On multivariate analysis, MFG-E8 level ≥4,745.1 pg/mL was an independent predictor for diagnosis and development of metabolic syndrome after adjusting other factors (all P<0.05).
Conclusions
Serum MFG-E8 level is a potent biomarker for the screening and prediction of metabolic syndrome.
8.Direct Bilirubin Is More Valuable than Total Bilirubin for Predicting Prognosis in Patients with Liver Cirrhosis
Han Ah LEE ; Joon Young JUNG ; Young-Sun LEE ; Young Kul JUNG ; Ji Hoon KIM ; Hyonggin AN ; Hyung Joon YIM ; Yoon Tae JEEN ; Jong Eun YEON ; Kwan Soo BYUN ; Soon Ho UM ; Yeon Seok SEO
Gut and Liver 2021;15(4):599-605
Background/Aims:
Most prognostic prediction models for patients with liver cirrhosis include serum total bilirubin (TB) level as a component. This study investigated prognostic performance of serum direct bilirubin (DB) and developed new DB level-based prediction models for cirrhosis.
Methods:
A total of 983 hospitalized patients with liver cirrhosis were included. DB-Model for End-Stage Liver Disease (MELD) score was calculated using MELD score formula, with serum DB level replacing TB level.
Results:
Mean age of study population was 56.1 years. Alcoholic liver disease was the most frequent underlying condition (471 patients, 47.9%). Within 6 months, 144 patients (14.6%) died or received liver transplantation due to severe liver dysfunction. The area under the receiver operating characteristic curve (AUROC) for prediction of 6-month mortality with DB level was significantly higher than that with TB level (p<0.001). The AUROC of DB-MELD score for prediction of 6-month mortality was significantly higher than that of MELD score (p<0.001). Patients were randomly divided into training (n=492) and validation (n=491) cohorts. A new prognostic prediction model, “Direct Bilirubin, INR, and Creatinine” (DiBIC) score, was developed based on the most significant predictors of 6-month mortality. In training set, AUROC of DiBIC score for prediction of 6-month mortality was 0.892, which was significantly higher than that of the MELD score (0.875, p=0.017), but not different from that of DB-MELD score (0.886, p=0.272). Similar results were observed in validation set.
Conclusions
New prognostic models, DB-MELD and DiBIC scores, have good prognostic performance in liver cirrhosis patients, outperforming other currently available models.
9.Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome
Han Ah LEE ; Jihwan LIM ; Hyung Joon JOO ; Young-Sun LEE ; Young Kul JUNG ; Ji Hoon KIM ; Hyunggin AN ; Hyung Joon YIM ; Yoon Tae JEEN ; Jong Eun YEON ; Do-Sun LIM ; Kwan Soo BYUN ; Yeon Seok SEO
Clinical and Molecular Hepatology 2021;27(3):463-473
Background/Aims:
Useful biomarkers for metabolic syndrome have been insufficient. We investigated the performance of serum milk fat globule-EGF factor-8 (MFG-E8), the key mediator of inflammatory pathway, in diagnosis of metabolic syndrome.
Methods:
Subjects aged between 30 and 64 years were prospectively enrolled in the Seoul Metabolic Syndrome cohort. Serum MFG-E8 levels were measured at baseline.
Results:
A total of 556 subjects were included, comprising 279 women (50.2%) and 277 men (49.8%). Metabolic syndrome was diagnosed in 236 subjects (42.4%), and the mean MFG-E8 level of subjects with metabolic syndrome was significantly higher than that of subjects without metabolic syndrome (P<0.001). MFG-E8 level was significantly correlated with all metabolic syndrome components and pulse wave velocity (all P<0.05). Subjects were categorized into two groups according to the best MFG-E8 cut-off value as follows: group 1, MFG-E8 level <4,745.1 pg/mL (n=401, 72.1%); and group 2, MFG-E8 level ≥4,745.1 (n=155, 27.9%). At baseline, metabolic syndrome in group 2 was significantly more prevalent than in group 1 (63.9% vs. 34.2%, P<0.001). During median follow-up of 17 months, metabolic syndrome developed in 122 (38.1%) subjects among 320 subjects without it at baseline. The incidence of metabolic syndrome in group 2 was significantly higher than that in group 1 (55.4% vs. 34.5%, P=0.003). On multivariate analysis, MFG-E8 level ≥4,745.1 pg/mL was an independent predictor for diagnosis and development of metabolic syndrome after adjusting other factors (all P<0.05).
Conclusions
Serum MFG-E8 level is a potent biomarker for the screening and prediction of metabolic syndrome.
10.Direct Bilirubin Is More Valuable than Total Bilirubin for Predicting Prognosis in Patients with Liver Cirrhosis
Han Ah LEE ; Joon Young JUNG ; Young-Sun LEE ; Young Kul JUNG ; Ji Hoon KIM ; Hyonggin AN ; Hyung Joon YIM ; Yoon Tae JEEN ; Jong Eun YEON ; Kwan Soo BYUN ; Soon Ho UM ; Yeon Seok SEO
Gut and Liver 2021;15(4):599-605
Background/Aims:
Most prognostic prediction models for patients with liver cirrhosis include serum total bilirubin (TB) level as a component. This study investigated prognostic performance of serum direct bilirubin (DB) and developed new DB level-based prediction models for cirrhosis.
Methods:
A total of 983 hospitalized patients with liver cirrhosis were included. DB-Model for End-Stage Liver Disease (MELD) score was calculated using MELD score formula, with serum DB level replacing TB level.
Results:
Mean age of study population was 56.1 years. Alcoholic liver disease was the most frequent underlying condition (471 patients, 47.9%). Within 6 months, 144 patients (14.6%) died or received liver transplantation due to severe liver dysfunction. The area under the receiver operating characteristic curve (AUROC) for prediction of 6-month mortality with DB level was significantly higher than that with TB level (p<0.001). The AUROC of DB-MELD score for prediction of 6-month mortality was significantly higher than that of MELD score (p<0.001). Patients were randomly divided into training (n=492) and validation (n=491) cohorts. A new prognostic prediction model, “Direct Bilirubin, INR, and Creatinine” (DiBIC) score, was developed based on the most significant predictors of 6-month mortality. In training set, AUROC of DiBIC score for prediction of 6-month mortality was 0.892, which was significantly higher than that of the MELD score (0.875, p=0.017), but not different from that of DB-MELD score (0.886, p=0.272). Similar results were observed in validation set.
Conclusions
New prognostic models, DB-MELD and DiBIC scores, have good prognostic performance in liver cirrhosis patients, outperforming other currently available models.

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