1.Tumor-Associated Macrophage Infiltration and PD-L1 Expression in Gastric Cancer According to a Modified TCGA-Based Classification
Boram SONG ; Dong-Hoe KOO ; Eo Jin KIM ; In-Gu DO ; Jinah CHU ; Kyungeun KIM ; Hyebin LEE ; Min-Jung KWON ; Jung Ho PARK ; Byung Ho SON ; Chang Hak YOO ; Seoung Wan CHAE
Journal of Gastric Cancer 2026;26(2):247-259
Purpose:
Although gastric cancer (GC) exhibits significant genomic heterogeneity, the clinical implications of its immune microenvironment remain poorly understood.
Materials and Methods:
We retrospectively evaluated patients with GC who underwent gastrectomies between 2011 and 2014. The tumors were analyzed for Epstein–Barr virus (EBV), microsatellite instability-high (MSI-H), tumor-infiltrating lymphocytes (CD3), tumor-associated macrophages (CD68 and CD163), and programmed death-ligand 1 (PD-L1) expression. Tumors were classified using the modified The Cancer Genome Atlas scheme, and their clinical characteristics were compared.
Results:
A total of 567 patients were classified into EBV (6%), MSI-H (10%), chromosomal instability-like (36%), and genomically stable-like (48%) subtypes. EBV tumors exhibited the highest PD-L1 expression (85%) and immune infiltration by CD3+ T cells (86%), CD68+ macrophages (58%), and CD163+ macrophages (40%). High CD68+ macrophage tumors were associated with advanced stages and worse 5-year disease-free survival (83% vs. 95%; P<0.001);however, this association was not independently significant after adjusting for the tumor-nodemetastasis stage. PD-L1 expression did not significantly affect the survival outcomes.
Conclusions
GC subtypes have distinct immune microenvironments that influence prognosis. Our findings highlight the prognostic and therapeutic potential of immune profiling in GC.
2.Real-World Efficacy of Intravesical Gemcitabine for BCG-Unresponsive Non–muscle-Invasive Bladder Cancer
Hye Won LEE ; Eui Hyun JUNG ; Kyung Hwan KIM ; Hong Koo HA ; Jong Jin OH ; Seok Ho KANG ; Seung-hwan JEONG ; Hyeong Dong YUK ; Ji Eun HEO ; Won Sik HAM ; Eu Chang HWANG ; Seung Il JUNG ; Wan SONG ; Bumjin LIM ; Bumsik HONG ; Byung Chang JEONG ; Ho Kyung SEO
Cancer Research and Treatment 2026;58(2):591-602
Purpose:
This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC).
Materials and Methods:
This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models.
Results:
Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course.
Conclusion
Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.
3.Human Understanding is Expected of the Physician: Proposing a Model of Disease Development
Sang-Heum PARK ; Samel PARK ; Jin Young KIM ; Hyeon Ah LEE ; Sang Mi LEE ; Tae Hoon LEE ; Sang Byung BAE ; Sung Hae CHANG ; Si Hyong JANG ; Sung Wan CHUN ; Jong Ho MOON
Korean Journal of Medicine 2025;100(1):44-
4.Effectiveness and Safety of Oral Quadruple Combination Therapy in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
Jaehyun BAE ; Min Heui YU ; Minyoung LEE ; Bong-Soo CHA ; Byung-Wan LEE
Endocrinology and Metabolism 2025;40(2):258-267
Background:
Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.
Methods:
This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge’s g) and the risk ratio for adverse events in random-effects meta-analyses.
Results:
The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist–containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.
Conclusion
Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.
5.Effectiveness and Safety of Oral Quadruple Combination Therapy in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
Jaehyun BAE ; Min Heui YU ; Minyoung LEE ; Bong-Soo CHA ; Byung-Wan LEE
Endocrinology and Metabolism 2025;40(2):258-267
Background:
Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.
Methods:
This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge’s g) and the risk ratio for adverse events in random-effects meta-analyses.
Results:
The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist–containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.
Conclusion
Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.
6.Human Understanding is Expected of the Physician: Proposing a Model of Disease Development
Sang-Heum PARK ; Samel PARK ; Jin Young KIM ; Hyeon Ah LEE ; Sang Mi LEE ; Tae Hoon LEE ; Sang Byung BAE ; Sung Hae CHANG ; Si Hyong JANG ; Sung Wan CHUN ; Jong Ho MOON
Korean Journal of Medicine 2025;100(1):44-
7.Effectiveness and Safety of Oral Quadruple Combination Therapy in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
Jaehyun BAE ; Min Heui YU ; Minyoung LEE ; Bong-Soo CHA ; Byung-Wan LEE
Endocrinology and Metabolism 2025;40(2):258-267
Background:
Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.
Methods:
This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge’s g) and the risk ratio for adverse events in random-effects meta-analyses.
Results:
The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist–containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.
Conclusion
Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.
8.Effectiveness and Safety of Oral Quadruple Combination Therapy in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
Jaehyun BAE ; Min Heui YU ; Minyoung LEE ; Bong-Soo CHA ; Byung-Wan LEE
Endocrinology and Metabolism 2025;40(2):258-267
Background:
Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.
Methods:
This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge’s g) and the risk ratio for adverse events in random-effects meta-analyses.
Results:
The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist–containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.
Conclusion
Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.
9.Human Understanding is Expected of the Physician: Proposing a Model of Disease Development
Sang-Heum PARK ; Samel PARK ; Jin Young KIM ; Hyeon Ah LEE ; Sang Mi LEE ; Tae Hoon LEE ; Sang Byung BAE ; Sung Hae CHANG ; Si Hyong JANG ; Sung Wan CHUN ; Jong Ho MOON
Korean Journal of Medicine 2025;100(1):44-
10.Human Understanding is Expected of the Physician: Proposing a Model of Disease Development
Sang-Heum PARK ; Samel PARK ; Jin Young KIM ; Hyeon Ah LEE ; Sang Mi LEE ; Tae Hoon LEE ; Sang Byung BAE ; Sung Hae CHANG ; Si Hyong JANG ; Sung Wan CHUN ; Jong Ho MOON
Korean Journal of Medicine 2025;100(1):44-

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