Background/Aims:Clinically useful noninvasive biomarkers for gastric cancer remain limited. Extracellular vesicles (EVs) carry a molecular cargo reflective of their cells of origin and have emerged as promising candidates for blood-based cancer biomarkers. We aimed to identify EV-associated protein biomarkers for gastric cancer via a proteomic approach. Methods:Proteomic profiling of EVs was performed using one normal gastric cell line (Hs738st/int) and two gastric cancer cell lines (AGS and NCI-N87). Selected proteins were validated in blood-derived EVs isolated from plasma samples of 10 healthy controls and 36 patients with gastric cancer. Results:Proteomic analysis identified 224 differentially expressed proteins whose expression was consistently altered in gastric cancer cell line-derived EVs. Among these, vitronectin (VTN) and laminin subunit alpha-3 (LAMA3) were selected based on their consistent upregulation. EV-associated LAMA3 levels were significantly higher in patients with gastric cancer than in healthy controls (p=0.003), with significant elevations observed from stage II onward (p=0.041, p=0.017, and p=0.004 for stages II, III, and IV, respectively). EV-associated VTN levels were not significantly different overall (p=0.089); however, stage-specific analysis demonstrated significant increases in VTN levels in patients with stage III (p=0.036) and stage IV (p=0.005) gastric cancer. Both EV-associated VTN and LAMA3 levels showed significant positive correlations with the cancer stage (ρ=0.564 and ρ=0.611, respectively; both p<0.001). Conclusions:The levels of EV-associated VTN and LAMA3 appear to be more closely associated with disease progression than with early-stage detection of gastric cancer. These findings suggest that EV-based proteomic biomarkers may have clinical utility for monitoring tumor progression in patients with clinically advanced gastric cancer.

Since the 2020 Korean guidelines for Helicobacter pylori treatment, clarithromycin resistance rates have risen from 17.8% to 33.3%, dual-priming oligonucleotide-based polymerase chain reaction-guided tailored therapy has been adopted, and potassium-competitive acid blockers (P-CABs) have become available. This fourth revision addressed these changes. Nine key questions were addressed through systematic review and meta-analysis. Thirteen recommendations were evaluated using a modified Delphi process involving 64 experts. Twelve recommendations achieved a first-round consensus; one required revision and achieved 73.9% agreement. Key changes included: 1) a dual-pillar strategy of tailored therapy and empirical quadruple therapy; 2) restricted use of empirical clarithromycin-based triple therapy under specific conditions; 3) removal of sequential therapy; 4) use of P-CABs as alternatives to proton pump inhibitors; 5) expansion of eradication indications to include gastric cancer prevention in H. pylori gastritis and regression of hyperplastic polyps ≤10 mm; and 6) positioning of bismuth quadruple therapy as a conditionally recommended first-line empirical option, with preference for reservation as salvage therapy, and introduction of modified bismuth quadruple therapy (addition of bismuth to conventional regimens) as an additional first-line empirical option. The revised guidelines provide updated evidence-based recommendations for the diagnosis and treatment of H. pylori infection, reflecting the rapidly changing antibiotic resistance landscape and the introduction of new diagnostic and therapeutic tools in Korea. These guidelines aim to assist clinicians, patients, policymakers, and medical educators in optimizing H. pylori management. They may differ from the current medical insurance standards and will be further revised based on emerging evidence.

An aortoesophageal fistula (AEF) is a rare but often fatal cause of upper gastrointestinal bleeding. Early diagnosis is challenging because clinical presentations are frequently atypical, which often leads to diagnostic delays. Here, we report the case of an 83-year-old man with an AEF in the mid-esophagus that appeared as a subepithelial tumor (SET)-like lesion. Endoscopic ultrasonography (EUS) revealed a heterogeneously hypoechoic lesion with multiple anechoic areas involving the submucosal and muscularis propria layers, raising concern for a possible malignant tumor. EUS-guided fine-needle biopsy resulted in blood spurting from the lesion, which was successfully controlled with endoscopic clipping. Subsequent contrast-enhanced chest CT confirmed a descending thoracic aortic aneurysm associated with an AEF, and emergency thoracic endovascular aortic repair was performed to prevent catastrophic hemorrhage. Therefore, when a SET-like lesion is detected in the mid-esophagus, careful assessment of pulsation through endoscopy and evaluation of aortic continuity and vascular flow using Doppler or contrast-enhanced EUS are essential for the early diagnosis of AEF.

Background/Objectives: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) is a promising tool for differentiating gastric subepithelial tumors (SETs). However, most published studies have mainly included gastrointestinal stromal tumors (GIST) and leiomyomas in the gastrointestinal tract, not limited to gastric SETs. This study evaluated the diagnostic performance of CH-EUS in gastric SETs encountered in clinical practice. Methods: We retrospectively analyzed 68 patients who underwent CH-EUS for gastric SETs between March 2021 and July 2025 at our institution. Gastric SETs were classified into benign (n = 27: ectopic pancreas, leiomyoma, schwannoma, glomus tumor, plexiform fibromyxoma, desmoid tumor, solitary fibrous tumor, and abscess) and GIST groups (n = 41). CH-EUS features, including arterial enhancement, irregular vessels, and diffuse enhancement, were assessed. Histopathological confirmation was obtained through EUS-guided fine-needle biopsy or endoscopic/surgical resection. Results: The GIST group showed significantly higher rates of arterial enhancement (95.1% vs. 74.1%, p = 0.024), irregular vessels (51.2% vs. 22.2%, p = 0.017), and diffuse enhancement (87.8% vs. 66.7%, p = 0.035) than the benign SETs. The diagnostic performance of arterial enhancement showed a sensitivity of 95.1% and specificity of 25.9%, while irregular vessels demonstrated a sensitivity of 51.2% and specificity of 77.8%, and diffuse enhancement showed a sensitivity of 87.8% and specificity of 33.3%. When combining ≥2 CH-EUS features, the sensitivity and specificity were 92.7% and 33.3%, respectively, with an overall accuracy of 69.1%. The presence of all three features yielded a specificity of 81.5% but a lower sensitivity (46.3%). Conclusions: CH-EUS exhibited a high sensitivity but low specificity in differentiating GISTs from various benign gastric SETs when using a combination of at least two CE-EUS features, including arterial enhancement, irregular vessels, and diffuse enhancement.

Helicobacter pylori (H. pylori) screening reduces the incidence and mortality of gastric cancer (GC). This study evaluated the cost-effectiveness of incorporating H. pylori screening into the Korean National Gastric Cancer Screening Program. A Markov model was developed to evaluate the cost-effectiveness of adding H. pylori screening to the existing national endoscopic screening program. The model simulated a virtual cohort of individuals aged ≥ 40 years and compared the current biennial endoscopy-only strategy (S1) with eight intervention strategies involving one-time or repeated H. pylori eradication at varying ages and intervals. Sensitivity analyses were performed to test the robustness of the results. All intervention strategies resulted in higher QALYs and costs than S1. H. pylori screening at age 40 (S2) was the most cost-effective (ICUR = 3,892,429 KRW/QALY). Other cost-effective strategies included H. pylori screening at ages 40 and 50 years (S5), every 6 years from ages 40 to 60 years (S9), and every 4 years during the same period (S8). Health outcome comparisons showed reductions in both cumulative cancer incidence and mortality with eradication-based strategies. Adding H. pylori screening to Korea’s national endoscopic screening program is a cost-effective strategy for the prevention of gastric cancer. These findings support the potential integration of screening into existing national screening policies, with implications for improving health outcomes and optimizing healthcare resource use.

The efficacy of clarithromycin-containing triple therapy (TT) against Helicobacter pylori has declined in Korea, with recent first-line eradication rates falling below 70%. Clarithromycin resistance exceeded 30%, undermining the standard regimen for H. pylori. These trends necessitate a change in the treatment strategy. This review analyzed the shift proposed in the draft of the 2025 Korean H. pylori guidelines. We examined the rationale for abandoning TT as a first-line empirical therapy and the establishment of a new dual-pillar strategy: 1) the declining role of clarithromycin-containing TT as a first-line treatment and 2) polymerase chain reaction (PCR)-based tailored therapy as the recommended precision approach. We explored the 1) emergence of new empirical regimen options, 2) application of tailored therapy, and 3) adoption of potassium-competitive acid blockers (P-CABs). Empirical regimens have shifted toward four-drug combinations to achieve higher cure rates. Concomitant therapy (proton-pump inhibitor [PPI] or P-CAB+amoxicillin+clarithromycin+metronidazole) offers high efficacy but raises concerns about antibiotic overuse. As a compromise, bismuth-augmented triple regimens (adding bismuth to TT) are now recommended; these modified quadruple therapies (e.g., PACB: PPI+amoxicillin+clarithromycin+bismuth, or PAMB: PPI+amoxicillin+metronidazole+bismuth) significantly improve eradication rates without requiring a third antibiotic class. Regarding tailored therapy, PCR-based domestic clinical research data consistently achieves ≥90% cure rates in first-line treatment—markedly higher than empirical TT in Korea. Economic analyses supported the cost-effectiveness of this approach. The guideline algorithm for salvage therapy was clarified. Bismuth quadruple therapy has been confirmed as the standard second-line treatment. For third-line therapy, we analyzed the efficacy of levofloxacin-based regimens, rifabutin-based therapy, and bismuth add-on therapy with two previously unused antibiotics. The 2025 Korean guidelines establish quadruple therapies as the new standard through a dual strategy: pragmatic empirical treatment and PCR-guided tailored therapy, with P-CABs and bismuth-based regimens as key components.

Subepithelial lesions (SELs) of the upper gastrointestinal tract are commonly detected during endoscopic examinations and encompass a broad spectrum of benign and potentially malignant tumors. Although most SELs are asymptomatic and found incidentally, accurate diagnosis remains challenging owing to their subepithelial location, necessitating advanced imaging and tissue acquisition techniques. Endoscopic ultrasonography plays a crucial role in differentiating SELs, although its diagnostic accuracy remains limited. The Korean College of Helicobacter and Upper Gastrointestinal Research has developed evidence-based practice guidelines for the diagnosis and endoscopic treatment of SELs to address the need for standardized clinical management. These guidelines were established through a systematic review of existing literature and expert consensus, resulting in 11 key recommendations for addressing diagnostic strategies, surveillance intervals, biopsy techniques, and indications for endoscopic or surgical resection.

Endoscopic submucosal dissection (ESD) has been established as the standard treatment for early gastric cancer, enabling en bloc resection regardless of lesion size and offering high curability with organ preservation. The indications for ESD have expanded with the accumulation of long-term data, and recent guidelines from Korea, Japan, and Western countries share similar criteria, although subtle differences regarding the undifferentiated-type histology remain. Despite its efficacy, ESD remains technically demanding, particularly for lesions with severe fibrosis or those located at difficult anatomical sites. Furthermore, as the population ages, perioperative management with antithrombotic agents has become a critical safety issue. This review provides a comprehensive overview of the current indications and clinical outcomes of ESD based on large-scale global data. It also offers practical strategies for overcoming technical difficulties and managing adverse events, with a specific focus on updated guidelines for antithrombotic agents and perforation management.

Proton pump inhibitors (PPIs) serve as the primary treatment for acid-related disorders, such as gastroesophageal reflux disease and peptic ulcer disease. Although PPIs are regarded as the first-line medication for acid suppression, they have notable limitations, including the need for acid-mediated activation, a short half-life and duration of action, and metabolic variability. Zastaprazan is a newly developed potassium-competitive acid blocker (P-CAB) that competitively and reversibly inhibits acid production and secretion. Like other P-CABs, zastaprazan exhibits pharmacodynamic and pharmacokinetic properties that differs significantly from those of PPIs. These differences offer potential advantages, such as rapid, robust, and long-standing acid suppression, the lack of CYP2C19 metabolism, and no need for conversion into an active form. Completed clinical trials of zastaprazan have demonstrated comparable or superior efficacy to that of PPIs for the healing of erosive esophagitis and gastric ulcers without concerning safety signals. Notably, in erosive esophagitis, zastaprazan 20 mg demonstrated faster healing at week 4 compared to esomeprazole 40 mg, whereas in gastric ulcers, zastaprazan 20 mg achieved a 100% healing rate at 8 weeks compared to 97.1% with lansoprazole 30 mg. Zastaprazan is approved in the Republic of Korea for the treatment of erosive esophagitis and gastric ulcer and is undergoing phase III clinical trials for the prevention of non-steroidal anti-inflammatory drug-induced peptic ulcer and the treatment of non-erosive reflux disease. In this review, we summarize and discuss the pharmacology, efficacy, and safety of zastaprazan in acid-related disorders.

Background/Aims: The prognostic value of serial 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) for patients with borderline resectable or locally advanced pancreatic cancer who undergo conversion surgery or continue chemotherapy without surgery has not been well-established. Methods: A retrospective analysis of patients with pancreatic ductal adenocarcinoma was conducted at Seoul National University Bundang Hospital between March 2013 and February 2022. Patients underwent PET/CT at baseline and subsequent radiologic evaluations following chemotherapy. Changes in the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume, and total lesion glycolysis were analyzed. Based on their treatment regimens, patients were stratified into the conversion surgery group or nonconversion surgery group. Survival outcomes and various clinical factors were assessed. Results: Among 121 patients, 52 underwent conversion surgery, and 69 continued to receive chemotherapy without surgery. A significant reduction in the SUVmax was correlated with prolonged recurrence-free survival and overall survival in the conversion surgery group. Confirmation of a pathologic response indicated a significant association between reductions in the SUVmax and positive outcomes. Reductions in the metabolic tumor volume and total lesion glycolysis were associated with improved progression-free survival and overall survival in the nonconversion surgery group. Conclusions: Serial PET/CT scans demonstrated prognostic value in pancreatic ductal adenocarcinoma patients, revealing distinct correlations in the conversion surgery group and nonconversion surgery group.

BackgroundIn Korea, the National Cancer Screening Program (NCSP) was implemented in 1999 and provides biennial endoscopy for adults aged ≥40 years. The NCSP has contributed to the early detection of gastric cancer and reduction of associated mortality in Korea. Helicobacter pylori is the main cause of gastric cancer. Screening for and eradication of H pylori reduces the incidence and mortality of gastric cancer. Previous studies have reported that screening for H pylori is a cost-saving intervention that can significantly decrease gastric cancer burden in areas with a high prevalence of H pylori infection. However, no study has examined whether incorporating H pylori screening into national endoscopic screening is cost effective. ObjectiveThis study aims to evaluate the cost-effectiveness of incorporating H pylori screening into Korea’s National Gastric Cancer Screening Program. MethodsWe have developed a Markov model to compare two strategies: (1) endoscopy screening every 2 years starting at the age of 40 years (conventional screening), and (2) H pylori screening at the age of 40 years followed by continuous endoscopy screening every 2 years. We will also conduct a comparative analysis by varying the age at which the H pylori screening is performed. The primary outcome is the incremental cost-utility ratio (ICUR), calculated by dividing the incremental cost by the incremental quality-adjusted life-years (QALYs) between the two strategies. A probabilistic sensitivity analysis will be performed to test the uncertainty of the cost-effectiveness results. A sensitivity analysis will identify the most influential variables for cost-effectiveness. ResultsThe primary outcome parameter is the cost-effectiveness of adding H pylori testing to the current NCSP, which is expressed as the ICUR. Costs and utilities are discounted at an annual rate of 4.5%. The ICUR threshold is set at KRW 50 million (US $36,719), which is the South Korean gross domestic product per capita. This research has been funded by a Patient-Centered Clinical Research Coordinating Center grant from the Ministry of Health & Welfare, Republic of Korea (grant RS-2024-00398474). This study will analyze and synthesize previously published information and is thus exempt from institutional review board approval. Data collection started in June 2024 and was completed in May 2025. Study results will be published in peer-reviewed journals and presented at national and international conferences throughout 2025. ConclusionsWe will examine whether introducing H pylori testing and eradication therapy into the NCSP is a more cost-effective strategy for reducing gastric cancer risk than conventional endoscopy-based screening. Our study also examines the optimal age for H pylori screening, as well as the optimal screening frequency. International Registered Report Identifier (IRRID)DERR1-10.2196/72228

Pusan National University Hospital, Korea (the Republic of).

The spontaneous regression (SR) of primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is extremely rare. Although the mechanism of SR is unclear, the host immune response, ischemia, or changes in the tumor microenvironment may play a role. On the other hand, SR does not indicate a complete cure and residual lymphoma may remain dormant, leading to relapse. This paper presents a rare case of an 82-year-old woman with PG-DLBCL who experienced SR without treatment, followed by a short-term relapse. In the present case, the most likely mechanism was biopsy-induced ischemia and increased apoptosis. This case underscores that, in PG-DLBCL with SR, the initial endoscopic findings are the most critical reference for an accurate diagnosis and proper management, but careful long-term follow-up and monitoring are necessary, given the risk of relapse.

Circulating tumor cells (CTCs) in cancer-draining veins have diagnostic and prognostic value. However, studies on esophageal squamous cell carcinoma (ESCC) are limited. This study aimed to compare CTCs obtained from different sampling sites (peripheral vein vs. cancer-draining azygos vein) and to investigate their association with the clinicopathological characteristics of ESCC patients. Blood samples were collected preoperatively from both veins in 40 ESCC patients at Pusan National University Hospital from June 2020 to April 2022. CTCs were detected using a centrifugal microfluidic method with fluid-assisted separation. CTCs and TWIST (+) CTCs were detected more frequently in the azygos vein blood than in the peripheral vein blood; however, the difference was not statistically significant (85.0% [34/40] vs. 77.5% [31/40], p = 0.250 and 82.5% [33/40] vs. 75.0% [30/40], p = 0.586, respectively). CTC and TWIST (+) CTC counts were significantly higher in the azygos vein blood than in the peripheral vein blood (7 vs. 3, p < 0.001, and 6 vs. 2, p < 0.001, respectively). CTCs and TWIST (+) CTCs from peripheral and azygos veins showed no association with clinicopathological characteristics. Further large-scale studies are needed to clarify their role as predictive biomarkers for prognosis and chemotherapy responses in ESCC patients.

This case report presents the successful endoscopic submucosal dissection (ESD) of a well-differentiated esophageal liposarcoma in a 51-year-old male with persistent dysphagia. The cause was initially diagnosed as a 10 cm pedunculated lesion extending from the upper esophageal sphincter to the mid-esophagus. An ESD was chosen over traditional surgery because it is less invasive. The procedure involved a precise submucosal injection and excision with special techniques to manage bleeding from a central vessel. Despite the extraction challenges owing to the size of the lesion, it was successfully removed orally. A histopathological examination of the 8.3×4.2×2.3 cm specimen revealed the characteristic features of a well-differentiated liposarcoma, including MDM2 and CDK4 positivity. The follow-up revealed no recurrence, and active surveillance has been performed since. This report highlights the versatility of ESD in treating significant esophageal tumors and provides evidence for its efficacy as a minimally invasive alternative.