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.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.
4.Clinical Implications of Circulating Tumor DNA in Multiple Myeloma and Its Precursor Diseases
Sung-Soo PARK ; Na Yung KIM ; Ji-Young LIM ; Jung Yeon LEE ; Sujin YUN ; Yeun-Jun CHUNG ; Seung-Hyun JUNG ; Chang-Ki MIN
Annals of Laboratory Medicine 2025;45(3):279-290
Background:
Genetic alterations play a pivotal role in multiple myeloma (MM) development and therapeutic resistance. Traditionally, the genetic profiling of MM requires invasive bone marrow (BM) procedures; however, these procedures are associated with patient discomfort and cannot fully capture the spatial and temporal heterogeneity of the disease.Therefore, we investigated the clinical implications of liquid biopsy using targeted deep sequencing.
Methods:
We analyzed the genetic profiles of circulating tumor DNA (ctDNA) by targeted deep sequencing from 102 patients, including those with monoclonal gammopathy of undetermined significance (MGUS, N = 7), smoldering MM (N = 6), and symptomatic MM (N = 89).
Results:
The number of ctDNA mutations increased with disease progression from MGUS to MM, with averages of 1.0 mutations in MGUS, 1.8 mutations in smoldering MM, and 1.9 mutations in MM, respectively. Shared mutations between BM and ctDNA were more prevalent in MM (68.9%) than in MGUS (25.0%). RAS/RAF and TP53 mutations were significantly enriched in MM ctDNA. Specific mutations were associated with clinical features in patients with MM: hypercalcemia and TET2 (P = 0.006), renal insufficiency and NRAS (P = 0.012), paramedullary myeloma and TP53(P = 0.02), and extramedullary myeloma and NRAS (P = 0.007). TET2 mutations significantly affected 2-yr progression-free survival (hazard ratio = 7.11, P = 0.003). Serial ctDNA profiling accurately predicted treatment response in patients with MM.
Conclusions
Our findings highlight the potential of liquid biopsy for understanding MM progression and prognosis utilizing a minimally invasive approach, paving the way for its integration into personalized treatment strategies and real-time disease monitoring.
5.Safety and Efficacy of Intravenous Thrombolysis in the 3- to 4.5-hour Window in Acute Ischemic Stroke Patients Who Have Both Diabetes Mellitus and History of Prior Stroke
Boyoung KIM ; Ji Sung LEE ; Hong-Kyun PARK ; Young Bok YUNG ; Ki Chang OH ; Jeong Joo PARK ; Yong-Jin CHO ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Hee-Joon BAE ; Tai Hwan PARK ; Sang-Soon PARK ; Kyung Bok LEE ; Jun LEE ; Byung-Chul LEE ; Minwoo LEE ; Joon-Tae KIM ; Kang-Ho CHOI ; Dong-Eog KIM ; Jay Chol CHOI ; Dong-Ick SHIN ; Jee-Hyun KWON ; Wook-Joo KIM ; Sung Il SOHN ; Jeong-Ho HONG ; Hyung Jong PARK ; Seong-Hwa JANG ; Kwang-Yeol PARK ; Sang-Hwa LEE ; Jong-Moo PARK ; Keun-Sik HONG
Journal of the Korean Neurological Association 2023;41(2):112-120
Background:
For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients.
Methods:
Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927).
Results:
The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]).
Conclusions
In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.
6.The Establishment of a Fast and Safe Orthotopic Colon Cancer Model Using a Tissue Adhesive Technique
Hong-Tao HU ; Zhe WANG ; Myung Ji KIM ; Lu-Shang JIANG ; Shi-Jun XU ; Jaeyun JUNG ; Eunji LEE ; Jung-Hoon PARK ; Nader BAKHEET ; Sung Hwan YOON ; Kun Yung KIM ; Ho-Young SONG ; Suhwan CHANG
Cancer Research and Treatment 2021;53(3):733-743
Purpose:
We aimed to develop a novel method for orthotopic colon cancer model, using tissue adhesive in place of conventional surgical method.
Materials and Methods:
RFP HCT 116 cell line were used to establish the colon cancer model. Fresh tumor tissue harvested from a subcutaneous injection was grafted into twenty nude mice, divided into group A (suture method) and group B (tissue adhesive method). For the group A, we fixed the tissue on the serosa layer of proximal colon by 8-0 surgical suture. For the group B, tissue adhesive (10 μL) was used to fix the tumor. The mortality, tumor implantation success, tumor metastasis, primary tumor size, and operation time were compared between the two groups. Dissected tumor tissue was analyzed for the histology and immunohistochemistry. Also, we performed tumor marker analysis.
Results:
We observed 30% increase in graft success and 20% decrease in mortality, by using tissue adhesive method, respectively. The median colon tumor size was significantly increased by 4 mm and operation time was shortened by 6.5 minutes. The H&E showed similar tumor structure between the two groups. The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups. Real-time quantitative reverse transcription analysis showed eight out of nine tumor markers are unchanged in the tissue adhesive group. Western blot indicated the tissue adhesive group expressed less p-JNK (apototic marker) and more p-MEK/p-p38 (proliferation marker) levels.
Conclusion
We concluded the tissue adhesive method is a quick and safe way to generate orthotopic, colon cancer model.
7.The Establishment of a Fast and Safe Orthotopic Colon Cancer Model Using a Tissue Adhesive Technique
Hong-Tao HU ; Zhe WANG ; Myung Ji KIM ; Lu-Shang JIANG ; Shi-Jun XU ; Jaeyun JUNG ; Eunji LEE ; Jung-Hoon PARK ; Nader BAKHEET ; Sung Hwan YOON ; Kun Yung KIM ; Ho-Young SONG ; Suhwan CHANG
Cancer Research and Treatment 2021;53(3):733-743
Purpose:
We aimed to develop a novel method for orthotopic colon cancer model, using tissue adhesive in place of conventional surgical method.
Materials and Methods:
RFP HCT 116 cell line were used to establish the colon cancer model. Fresh tumor tissue harvested from a subcutaneous injection was grafted into twenty nude mice, divided into group A (suture method) and group B (tissue adhesive method). For the group A, we fixed the tissue on the serosa layer of proximal colon by 8-0 surgical suture. For the group B, tissue adhesive (10 μL) was used to fix the tumor. The mortality, tumor implantation success, tumor metastasis, primary tumor size, and operation time were compared between the two groups. Dissected tumor tissue was analyzed for the histology and immunohistochemistry. Also, we performed tumor marker analysis.
Results:
We observed 30% increase in graft success and 20% decrease in mortality, by using tissue adhesive method, respectively. The median colon tumor size was significantly increased by 4 mm and operation time was shortened by 6.5 minutes. The H&E showed similar tumor structure between the two groups. The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups. Real-time quantitative reverse transcription analysis showed eight out of nine tumor markers are unchanged in the tissue adhesive group. Western blot indicated the tissue adhesive group expressed less p-JNK (apototic marker) and more p-MEK/p-p38 (proliferation marker) levels.
Conclusion
We concluded the tissue adhesive method is a quick and safe way to generate orthotopic, colon cancer model.
8.Current Status of Patient Education in the Management of Atopic Dermatitis in Korea
Min Kyung LEE ; Ju Hee SEO ; Howard CHU ; Hyunjung KIM ; Yong Hyun JANG ; Jae Won JEONG ; Hye Yung YUM ; Man Yong HAN ; Ho Joo YOON ; Sang Heon CHO ; Yeong Ho RHA ; Jin Tack KIM ; Young Lip PARK ; Seong Jun SEO ; Kwang Hoon LEE ; Chang Ook PARK
Yonsei Medical Journal 2019;60(7):694-699
Patient education is important for successful management of atopic dermatitis; however, due to limited time and resources, patient education remains insufficient. This study aimed to investigate the current state of education provided by Korean dermatologists, pediatric allergists, and allergists to patients with atopic dermatitis. A questionnaire survey consisting of items regarding educational programs for patients with atopic dermatitis was conducted via e-mail. In total, 153 participants responded to the questionnaires, and 26.8% indicated that they have had separate educational programs. The workforce involved in the educational program included nurses, residents or fellows, dieticians, pharmacists, and clinical psychologists. Most education protocols addressed the characteristics and natural course of atopic dermatitis and environmental management. Overall, 96.7% of the participants replied that an additional charge is needed for education; moreover, additional assistance from an academic society or association, in the form of medical staff, organized data, and advertisement, is required to develop and provide a well-structured educational program. A standardized education protocol will effectively provide appropriate education for patients with atopic dermatitis. Arrangement of education fees, covered by the National Health Insurance Service, will lead to the establishment of a structured educational program and participation of an additional medical workforce.
Dermatitis, Atopic
;
Education
;
Electronic Mail
;
Fees and Charges
;
Humans
;
Korea
;
Medical Staff
;
National Health Programs
;
Nutritionists
;
Patient Education as Topic
;
Pharmacists
;
Psychology
9.Three-dimensional accuracy of different correction methods for cast implant bars.
Ji Yung KWON ; Chang Whe KIM ; Young Jun LIM ; Ho Beom KWON ; Myung Joo KIM
The Journal of Advanced Prosthodontics 2014;6(1):39-45
PURPOSE: The aim of the present study was to evaluate the accuracy of three techniques for correction of cast implant bars. MATERIALS AND METHODS: Thirty cast implant bars were fabricated on a metal master model. All cast implant bars were sectioned at 5 mm from the left gold cylinder using a disk of 0.3 mm thickness, and then each group of ten specimens was corrected by gas-air torch soldering, laser welding, and additional casting technique. Three dimensional evaluation including horizontal, vertical, and twisting measurements was based on measurement and comparison of (1) gap distances of the right abutment replica-gold cylinder interface at buccal, distal, lingual side, (2) changes of bar length, and (3) axis angle changes of the right gold cylinders at the step of the post-correction measurements on the three groups with a contact and non-contact coordinate measuring machine. One-way analysis of variance (ANOVA) and paired t-test were performed at the significance level of 5%. RESULTS: Gap distances of the cast implant bars after correction procedure showed no statistically significant difference among groups. Changes in bar length between pre-casting and post-correction measurement were statistically significance among groups. Axis angle changes of the right gold cylinders were not statistically significance among groups. CONCLUSION: There was no statistical significance among three techniques in horizontal, vertical and axial errors. But, gas-air torch soldering technique showed the most consistent and accurate trend in the correction of implant bar error. However, Laser welding technique, showed a large mean and standard deviation in vertical and twisting measurement and might be technique-sensitive method.
Axis, Cervical Vertebra
;
Welding
10.Predictors for the Failure of Expectant Management for the Spontaneous Passage of Ureteral Calculi.
Chan Hee LEE ; Yung Kap KIM ; Sang Hyun PARK ; Ju Taek LEE ; Chang Jae LEE ; Ok Jun KIM ; Sung Wook CHOI ; Eui Chung KIM ; Tae Nyoung CHUNG ; Jin Kun BAE
Journal of the Korean Society of Emergency Medicine 2013;24(4):403-409
PURPOSE: Ureteral calculi are commonly encountered in the emergency department. Ureteral calculi influence the quality of life of patients, causing pain and economic burden. The optimal management of ureteral calculi remains a challenge for practicing physicians; therefore, this study was designed to determine which factors are related to the failure of their spontaneous passage. METHODS: This study was a retrospective review of the medical records of one hundred ninety-five patients who visited the emergency department complaining of renal colic from February 2012 to December 2012. Bivariate analyses were conducted relating physical, laboratory, and radiological methods to predict the failure of spontaneous passage. A multivariate logistic regression model was then derived, with all variables in the final model significant at p<0.05. RESULTS: One hundred twenty-eight stones were spontaneously expelled and sixty-seven were not. The mean stone size was significantly larger in the non-passage group than the passage group (p<0.001). When the stones were located in the upper ureter, or on the right side, the spontaneous passage rate was lower (p<0.001, p=0.035). Increased neutrophils and positive tests for urinary protein and bilirubin were also associated with the decreased likelihood of spontaneous passage (p=0.046, p=0.029, and p=0.048, respectively). In addition, the longer duration of symptoms and a previous history of ureteral calculi were related to a lower chance of spontaneous passage (p=0.005, p=0.019). CONCLUSION: Prognostic factors of failure, after the initial expectant management of ureteral calculi, included: calculi size, location (e.g., side), the duration of symptoms, the previous history, neutrophil levels, urinary bilirubin levels, and urinary protein levels. Therefore, emergency physicians need to cautiously decide between watchful waiting and interventions in these patients.
Bilirubin
;
Calculi
;
Emergencies
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Humans
;
Logistic Models
;
Medical Records
;
Neutrophils
;
Quality of Life
;
Renal Colic
;
Retrospective Studies
;
Ureter
;
Ureteral Calculi
;
Watchful Waiting

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