Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Background/Aims: Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases.This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

Background: Sutureless valves are widely used in aortic valve replacement surgery, with Perceval valves and Intuity valves being particularly prominent. However, concerns have been raised about postoperative thrombocytopenia with Perceval valves (Corcym, UK). We conducted a comparative analysis with the Intuity valve (Edwards Lifesciences, USA), and assessed how thrombocytopenia affected patient and transfusion outcomes. Methods: Among 595 patients who underwent aortic valve replacement from June 2016 to March 2023, sutureless valves were used in 53 (Perceval: n=23; Intuity: n=30). Platelet counts were monitored during hospitalization and outpatient visits. Daily platelet count changes were compared between groups, and the results from patients who underwent procedures using Carpentier Edwards Perimount Magna valves were used as a reference group. Results: Compared to the Intuity group, the Perceval group showed a significantly higher amount of platelet transfusion (5.48±1.64 packs vs. 0.60±0.44 packs, p=0.008). During the postoperative period, severe thrombocytopenia (<50,000/μL) was significantly more prevalent in the Perceval group (56.5%, n=13) than in the Intuity group (6.7%, n=2). After initial postoperative depletion, daily platelet counts increased, with significant differences observed in the extent of improvement between the Perceval and Intuity groups (p<0.001).However, there was no significant difference in early mortality or the incidence of neurological complications between the 2 groups. Conclusion The severity of postoperative thrombocytopenia differed significantly between the Perceval and Intuity valves. The Perceval group showed a significantly higher prevalence of severe thrombocytopenia and higher platelet transfusion volumes. However, thrombocytopenia gradually recovered during the postoperative period in both groups, and the early outcomes were similar in both groups.

Background/Aims: To date, studies on various noninvasive techniques have been suggested to evaluate the degree of liver fibrosis. We aimed to investigate the diagnostic performance of se-rum asialo α1-acid glycoprotein (AsAGP) in the diagnosis of liver cirrhosis compared with chronic hepatitis for clinically useful result. Methods: We conducted a case-control study of 96 patients with chronic liver disease. Chronic hepatitis was defined as the presence of chronic liver disease on ultrasonography, with a liver stiffness of less than 5.0 kPa as shown on magnetic resonance elastography (MRE). Liver cirrho-sis was defined as liver stiffness of more than 5.0 kPa on MRE. The serum AsAGP concentration was compared between the two groups. Results: Serum AsAGP levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis (1.83 μg/mL vs 1.42 μg/mL, p<0.001). Additionally, when comparing pa-tients in each cirrhotic group (Child-Pugh grades A, B, and C) to those with chronic hepatitis, AsAGP levels were significantly higher in all the cirrhotic groups (p<0.05, p<0.01, p<0.001, respectively). The sensitivity and specificity of AsAGP for detecting cirrhosis were 79.2% and 64.6%, respectively, and the area under the curve value was 0.733. The best diagnostic cutoff to predict cirrhosis was 1.4 μg/mL. AsAGP and bilirubin were found to be independent risk factors for the prediction of cirrhosis in the logistic regression analysis. Conclusions Serum AsAGP showed an acceptable diagnostic performance in predicting liver cirrhosis.

Background/Aims: Subepithelial tumors (SETs) are small, mostly asymptomatic lesions with normal overlying mucosa, usually identified incidentally on endoscopy. The aim of this study was to evaluate the pathologic diagnosis of SETs, and to assess the diagnostic yield and impact of endoscopic submucosal dissection (ESD) biopsy on the management of patients with SETs. Materials and Methods: We included 52 subepithelial lesions in this study during the study period. Inclusion criteria included size of the SET >2 cm, and a gastrointestinal stromal tumor (GIST) that cannot be excluded using EUS. We performed an endoscopic biopsy of each SET using the ESD technique. Results: The mean diameter of the lesions was 24.15±6.0 mm. The diagnostic yield of this method was 96.15%. Among the 52 participants, 45 were located in the stomach, four in the esophagus, and three in the duodenum. The pathologic diagnoses included: 17 leiomyomas, 13 GISTs, 11 ectopic pancreases, two carcinomas, two inflammatory fibroid polyps, two Brunner’s gland hyperplasia, two lipomas, one glomus tumor, and two remained undiagnosed. The mean duration of the procedure was 13.44±2.41 minutes. Three complications were associated with the procedure. Conclusions Deep biopsy via ESD is useful in determining the histopathologic nature of SETs. This method minimizes the need for unnecessary surgery in benign SETs.

Background/Aims: Subepithelial tumors (SETs) are small, mostly asymptomatic lesions with normal overlying mucosa, usually identified incidentally on endoscopy. The aim of this study was to evaluate the pathologic diagnosis of SETs, and to assess the diagnostic yield and impact of endoscopic submucosal dissection (ESD) biopsy on the management of patients with SETs. Materials and Methods: We included 52 subepithelial lesions in this study during the study period. Inclusion criteria included size of the SET >2 cm, and a gastrointestinal stromal tumor (GIST) that cannot be excluded using EUS. We performed an endoscopic biopsy of each SET using the ESD technique. Results: The mean diameter of the lesions was 24.15±6.0 mm. The diagnostic yield of this method was 96.15%. Among the 52 participants, 45 were located in the stomach, four in the esophagus, and three in the duodenum. The pathologic diagnoses included: 17 leiomyomas, 13 GISTs, 11 ectopic pancreases, two carcinomas, two inflammatory fibroid polyps, two Brunner’s gland hyperplasia, two lipomas, one glomus tumor, and two remained undiagnosed. The mean duration of the procedure was 13.44±2.41 minutes. Three complications were associated with the procedure. Conclusions Deep biopsy via ESD is useful in determining the histopathologic nature of SETs. This method minimizes the need for unnecessary surgery in benign SETs.

Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

Tyrosine kinase inhibitors are widely used as targeted treatments for various malignancies. Sorafenib is an orally active tyrosine kinase inhibitor that blocks the signaling pathways of several growth factors. Its use is approved for various malignancies such as unresectable hepatocellular carcinoma, renal cell carcinoma, and gastrointestinal stromal tumors. Several adverse effects have been reported in the literature; however, cardiotoxicity is rare. We present a case of recurrent coronary vasospasm caused by short-term administration (5 days) of sorafenib. Since it caused refractory ischemia after re-administration, we had no choice but to stop the treatment.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic

Exercise capacity is a valuable trait in horses, and it has been used as a horse selection criterion. Although exercise affects molecular homeostasis and adaptation in horses, the mechanisms underlying these effects are not fully described. This study was carried out to identify changes in the blood profiles of microRNAs (miRNAs) and mRNAs induced by exercise in horse leukocytes. Total RNAs isolated from the peripheral blood leukocytes of four Warmblood horses before and after exercise were subjected to next-generation sequencing (NGS) and microarray analyses to determine the miRNA and mRNA expression profiles, respectively. The expressions of 6 miRNAs, including 4 known and 2 novel miRNAs, were altered by exercise. The predicted target genes of the differentially expressed miRNAs identified by NGS were matched to the exercise-induced mRNAs determined by microarray analysis. Five genes (LOC100050849, LOC100054517, KHDRBS3, LOC100053996, and LOC100062720) from the microarray analysis were matched to the predicted target genes of the 6 miRNAs. The subset of mRNAs and miRNAs affected by exercise in peripheral blood leukocytes may be useful in elucidating the molecular mechanisms of exercise-associated physiology in horses.
Homeostasis ; Horses ; Leukocytes ; Microarray Analysis ; MicroRNAs ; Physiology ; RNA ; RNA, Messenger