1.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
2.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
3.Weight fluctuation and incidence of end-stage renal disease in Korea: a nationwide cohort study
Koh-Eun SHIN ; Byoungduck HAN ; Gyu Bae LEE ; Jihyun YOON ; Kyungdo HAN ; Yang-Hyun KIM
Cardiovascular Prevention and Pharmacotherapy 2025;7(2):28-37
Background:
The impact of weight or weight changes on kidney function remains a matter of debate. This study aimed to investigate the association between weight fluctuation and the incidence of end-stage renal disease (ESRD) using data from the Korean National Health Insurance Corporation health checkups (2009–2015).
Methods:
The study included 2,310,667 participants (1,546,749 men and 763,918 women), aged ≥40 years. Weight fluctuation was assessed using the average real variability (ARV) of weight and categorized into quartiles (Q1–Q4). Hazard ratios (HRs) and 95% confidence intervals for ESRD incidence were calculated using multivariable Cox proportional hazards models.
Results:
After adjustment for comorbidities, increased body mass index was associated with a decreased HR for ESRD. The highest quartile of weight variability (ARV Q4) demonstrated a higher probability and HR for ESRD compared to the lower variability quartiles (Q1–Q3). Among men, individuals with sustained weight, and those with weight gain, the ARV Q4 group showed significantly increased HRs for ESRD (HR of 1.372, 1.222, and 1.49, respectively). Furthermore, irrespective of changes in creatinine levels, all ARV Q4 groups exhibited increased HRs for ESRD (HR of 1.342, 1.472, and 1.299, respectively).
Conclusions
High weight fluctuation (ARV Q4) was associated with an increased incidence of ESRD in the general Korean population, with notable significance in men and in groups with sustained or increased weight. Clinically, individuals in the ARV Q4 category should be considered at risk for ESRD, and early interventions should be pursued for this population.
4.Statins: a tale of two pathways—cardiovascular savior, renal ineffectual
Precision and Future Medicine 2025;9(1):43-52
Statins are effective in improving outcomes in the general population. However, in patients with chronic kidney disease (CKD), clinical outcomes and therapeutic approaches require careful interpretation from multiple perspectives. Managing dyslipidemia in CKD presents unique challenges requiring a comprehensive understanding of alterations in lipid metabolism in renal dysfunction. This review explored the key factors influencing statin efficacy, safety, and guideline recommendations in the CKD population, with a focus on lipid-lowering strategies tailored to renal function.
5.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
6.Therapeutic Effect of Anti-inflammatory Tripeptide Cream in Hand-Foot Syndrome/Skin Reaction Related to Anticancer Drugs: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial
Yaewon YANG ; Jang-Hee HAHN ; Min Seo KIM ; Minkwan JO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Jihyun KWON ; Ki Hyeong LEE ; Hye Sook HAN
Cancer Research and Treatment 2024;56(4):1050-1057
Purpose:
Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are relatively common toxicities that interfere with the quality of life (QoL) of patients with cancer. Anti-inflammatory tripeptide cream (ATPC) is a complex formulation of anti-inflammatory tripeptides, the CD99-agonist Binterin and the Wnt-antagonist Winhibin. The present study aimed to assess the therapeutic effects of ATPC in HFS/HFSR associated with anticancer drugs.
Materials and Methods:
This was a single-center, randomized, double-blind, placebo-controlled trial. Patients who developed grade 1 HFS/HFSR after systemic anticancer treatments were enrolled, and randomly assigned to receive either ATPC or placebo cream (PC) and followed up at 3-week intervals for up to 9 weeks. Primary endpoint was the development of grade ≥ 2 HFS/HFSR.
Results:
Between April 2019 and July 2022, 60 patients (31 in the ATPC and 29 in the PC group) completed the study. The incidence of grade ≥ 2 HFS/HFSR was significantly lower in the ATPC than in the PC group (25.8% vs. 51.7%, p=0.039). The ATPC showed trends towards a better QoL score, assessed by a HFSR and QoL questionnaire at 9 weeks (26.0 vs. 29.9, p=0.574), and a lower frequency of discontinuation, interruption, or dose reduction of anticancer drugs (51.6% vs. 58.6%, p=0.586) than the PC group over 9 weeks, though without statistical significance.
Conclusion
Our results showed that ATPC significantly decreased the development of grade ≥ 2 HFS/HFSR in patients already with HFS/HFSR. Therefore, ATPC may be an effective treatment for HFS/HFSR associated with anticancer drugs.
7.Identification of acute myocardial infarction and stroke events using the National Health Insurance Service database in Korea
Minsung CHO ; Hyeok-Hee LEE ; Jang-Hyun BAEK ; Kyu Sun YUM ; Min KIM ; Jang-Whan BAE ; Seung-Jun LEE ; Byeong-Keuk KIM ; Young Ah KIM ; JiHyun YANG ; Dong Wook KIM ; Young Dae KIM ; Haeyong PAK ; Kyung Won KIM ; Sohee PARK ; Seng Chan YOU ; Hokyou LEE ; Hyeon Chang KIM
Epidemiology and Health 2024;46(1):e2024001-
OBJECTIVES:
The escalating burden of cardiovascular disease (CVD) is a critical public health issue worldwide. CVD, especially acute myocardial infarction (AMI) and stroke, is the leading contributor to morbidity and mortality in Korea. We aimed to develop algorithms for identifying AMI and stroke events from the National Health Insurance Service (NHIS) database and validate these algorithms through medical record review.
METHODS:
We first established a concept and definition of “hospitalization episode,” taking into account the unique features of health claims-based NHIS database. We then developed first and recurrent event identification algorithms, separately for AMI and stroke, to determine whether each hospitalization episode represents a true incident case of AMI or stroke. Finally, we assessed our algorithms’ accuracy by calculating their positive predictive values (PPVs) based on medical records of algorithm- identified events.
RESULTS:
We developed identification algorithms for both AMI and stroke. To validate them, we conducted retrospective review of medical records for 3,140 algorithm-identified events (1,399 AMI and 1,741 stroke events) across 24 hospitals throughout Korea. The overall PPVs for the first and recurrent AMI events were around 92% and 78%, respectively, while those for the first and recurrent stroke events were around 88% and 81%, respectively.
CONCLUSIONS
We successfully developed algorithms for identifying AMI and stroke events. The algorithms demonstrated high accuracy, with PPVs of approximately 90% for first events and 80% for recurrent events. These findings indicate that our algorithms hold promise as an instrumental tool for the consistent and reliable production of national CVD statistics in Korea.
8.Reply: Does Acupuncture Increase the Risk of Hepatitis C Virus Transmission?A Commentary on the Currently Published Article, “Risk of Hepatitis C Virus Transmission through Acupuncture: A Systematic Review and Meta-Analysis”
Myung Han HYUN ; Hyun YANG ; Jihyun AN
The Korean Journal of Gastroenterology 2024;83(2):72-73
9.Risk of Hepatitis C Virus Transmission through Acupuncture: A Systematic Review and Meta-Analysis
Myung Han HYUN ; Ji Hoon KIM ; Jeong Won JANG ; Jeong Eun SONG ; Do Seon SONG ; Hye Won LEE ; Young Youn CHO ; Gi-Ae KIM ; Eileen L. YOON ; Dong Hyun SINN ; Soon Sun KIM ; Sun Young YIM ; Hyun YANG ; Jihyun AN
The Korean Journal of Gastroenterology 2023;82(3):127-136
Background/Aims:
Chronic hepatitis C is a major risk factor for liver cirrhosis, hepatocellular carcinoma, and hepatic failure. Although traditional practices, including acupuncture, tend to increase the risk of HCV infection, the association remains controversial. Therefore, the current meta-analytical study was undertaken to evaluate the risks of acupuncture and hepatitis C transmission.
Methods:
Two researchers independently screened studies from the databases encompassing the period from inception to May 12, 2022. Baseline demographics, HCV transmission OR, and 95% CIs were extracted, pooled, and analyzed using random-effect models.Subgroup analyses utilizing study design and ethnicity were performed. Heterogeneity and publication bias were analyzed using the Higgins I2 test and funnel plots, respectively.
Results:
In all, 28 studies with 194,826 participants (178,583 controls [91.7%] vs. 16,243 acupuncture users [8.3%]) were included in the final analysis. The pooled analysis showed that acupuncture users had a significantly higher HCV transmission rate than controls with heterogeneity (OR, 1.84 [1.46–2.32]; p<0.001; I2 =80%). In the subgroup analysis, both cross-sectional case-control (n=14; OR, 1.96 [1.47–2.61]; p<0.001; I2 =88%) and cross-sectional studies (n=12; OR, 1.85 [1.32–2.61]; p<0.001; I2 =0%) showed significantly higher HCV infection rates in the acupuncture group than in the control group. Both Asian and non-Asian acupuncture users showed a higher HCV transmission risk than the controls (all Ps <0.001). No significant publication bias was observed.
Conclusions
Our findings indicate that acupuncture increases the risk of HCV transmission. Due to HCV's contagiousness, unsafe medical and social practices (including acupuncture) should be performed with caution.
10.Clinical Characteristics of Atopic Dermatitis in Korean School-Aged Children and Adolescents According to Onset Age and Severity
You Hoon JEON ; Kangmo AHN ; Jihyun KIM ; Meeyong SHIN ; Soo-Jong HONG ; So-Yeon LEE ; Bok Yang PYUN ; Taek Ki MIN ; Minyoung JUNG ; Jeongmin LEE ; Tae Won SONG ; Hye-Young KIM ; Sooyoung LEE ; Kyunguk JEONG ; Yoonha HWANG ; Minji KIM ; Yong Ju LEE ; Min Jung KIM ; Ji Young LEE ; Hye Yung YUM ; Gwang Cheon JANG ; Young A PARK ; Jeong Hee KIM ;
Journal of Korean Medical Science 2022;37(4):e30-
Background:
Atopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea.
Methods:
AD patients aged 6–18 years who presented to 18 hospitals nationwide were surveyed.The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites,treatment history and quality of life were collected. The results of the patient’s allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschoolonset (2–5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups.
Results:
A total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancyonset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group.
Conclusion
This study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.

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