Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Purpose: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal complication of gastric cancer (GC). This study aimed to evaluate the clinical characteristics, outcomes, and immunohistochemical profiles of patients with GC-induced PTTM. Materials and Methods: From 2011 to 2023, 8 patients were clinically diagnosed with PTTM associated with GC antemortem. Clinical features and outcomes were reviewed, and immunohistochemical staining for c-erbB-2, MutL protein homolog 1, and programmed cell death ligand-1 was performed. Results: The median patient age was 56 years (range, 34–66 years). In all the patients, the tumors exhibited either ulceroinfiltrative or diffusely infiltrative gross morphology.The median tumor size was 5.8 cm (range, 2.0 cm–15.0 cm). Poorly differentiated adenocarcinoma was the most common histological type (6/8, 75%), followed by signet ring cell carcinoma (1/8, 12.5%) and moderately differentiated adenocarcinoma (1/8, 12.5%).Chest computed tomography revealed ground-glass opacities (7/8, 87.5%) or tree-in-bud signs (2/8, 25.0%) without definite evidence of pulmonary thromboembolism. Disseminated intravascular coagulation was present in 62.5% (5/8) of the patients diagnosed with PTTM.C-erbB-2 was positive in one patient (1/8, 12.5%). One patient who received palliative chemotherapy after developing PTTM survived for 35 days, whereas the other 7 patients who did not receive chemotherapy after developing PTTM survived for 7 days or less after PTTM diagnosis. Conclusions Most patients with GC-induced PTTM had an undifferentiated-type histology, infiltrative morphology, and extremely poor survival. Palliative chemotherapy may benefit patients with GC-induced PTTM; however, further studies are needed to explore the potential of targeted therapy in these patients.

Purpose: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal complication of gastric cancer (GC). This study aimed to evaluate the clinical characteristics, outcomes, and immunohistochemical profiles of patients with GC-induced PTTM. Materials and Methods: From 2011 to 2023, 8 patients were clinically diagnosed with PTTM associated with GC antemortem. Clinical features and outcomes were reviewed, and immunohistochemical staining for c-erbB-2, MutL protein homolog 1, and programmed cell death ligand-1 was performed. Results: The median patient age was 56 years (range, 34–66 years). In all the patients, the tumors exhibited either ulceroinfiltrative or diffusely infiltrative gross morphology.The median tumor size was 5.8 cm (range, 2.0 cm–15.0 cm). Poorly differentiated adenocarcinoma was the most common histological type (6/8, 75%), followed by signet ring cell carcinoma (1/8, 12.5%) and moderately differentiated adenocarcinoma (1/8, 12.5%).Chest computed tomography revealed ground-glass opacities (7/8, 87.5%) or tree-in-bud signs (2/8, 25.0%) without definite evidence of pulmonary thromboembolism. Disseminated intravascular coagulation was present in 62.5% (5/8) of the patients diagnosed with PTTM.C-erbB-2 was positive in one patient (1/8, 12.5%). One patient who received palliative chemotherapy after developing PTTM survived for 35 days, whereas the other 7 patients who did not receive chemotherapy after developing PTTM survived for 7 days or less after PTTM diagnosis. Conclusions Most patients with GC-induced PTTM had an undifferentiated-type histology, infiltrative morphology, and extremely poor survival. Palliative chemotherapy may benefit patients with GC-induced PTTM; however, further studies are needed to explore the potential of targeted therapy in these patients.

Purpose: Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal complication of gastric cancer (GC). This study aimed to evaluate the clinical characteristics, outcomes, and immunohistochemical profiles of patients with GC-induced PTTM. Materials and Methods: From 2011 to 2023, 8 patients were clinically diagnosed with PTTM associated with GC antemortem. Clinical features and outcomes were reviewed, and immunohistochemical staining for c-erbB-2, MutL protein homolog 1, and programmed cell death ligand-1 was performed. Results: The median patient age was 56 years (range, 34–66 years). In all the patients, the tumors exhibited either ulceroinfiltrative or diffusely infiltrative gross morphology.The median tumor size was 5.8 cm (range, 2.0 cm–15.0 cm). Poorly differentiated adenocarcinoma was the most common histological type (6/8, 75%), followed by signet ring cell carcinoma (1/8, 12.5%) and moderately differentiated adenocarcinoma (1/8, 12.5%).Chest computed tomography revealed ground-glass opacities (7/8, 87.5%) or tree-in-bud signs (2/8, 25.0%) without definite evidence of pulmonary thromboembolism. Disseminated intravascular coagulation was present in 62.5% (5/8) of the patients diagnosed with PTTM.C-erbB-2 was positive in one patient (1/8, 12.5%). One patient who received palliative chemotherapy after developing PTTM survived for 35 days, whereas the other 7 patients who did not receive chemotherapy after developing PTTM survived for 7 days or less after PTTM diagnosis. Conclusions Most patients with GC-induced PTTM had an undifferentiated-type histology, infiltrative morphology, and extremely poor survival. Palliative chemotherapy may benefit patients with GC-induced PTTM; however, further studies are needed to explore the potential of targeted therapy in these patients.

Background/Aims: Delayed perforation is a rare but serious adverse event of gastric endoscopic submucosal dissection (ESD). The aim of this study was to clarify the clinical features and appropriate management strategy of patients with delayed perforation. Methods: Among 11,531 patients who underwent gastric ESD, the clinical features and outcomes of patients who experienced delayed perforation were retrospectively reviewed and compared with those of the control group. Results: Delayed perforation occurred in 15 of 11,531 patients (0.13%). The patients with delayed perforation were significantly older than those without delayed perforation (p=0.027). The median time to diagnosis of delayed perforation was 28.8 hours (range, 14 to 71 hours). All 15 patients with delayed perforation complained of severe abdominal pain after gastric ESD and underwent subsequent chest X-rays (CXRs) for evaluation. In subsequent CXR, free air was found in 12 patients (80%). For three (20%) patients without free air in CXR, delayed perforation was finally diagnosed by computed tomography. Leukocytosis was significantly less frequent in the patients without free air in CXR (p=0.022). A perforation hole smaller than 1 cm in size was more frequently observed in the six patients who underwent successful non-surgical treatments than in the nine patients who underwent surgery (p<0.001). There was no mortality related to delayed perforation. Conclusions One-fifth of the patients with delayed perforation did not show free air in CXR and exhibited less leukocytosis than those with free air. Non-surgical treatments including endoscopic closure might be considered as an initial treatment modality for delayed perforation smaller than 1 cm.

Background/Aims: Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of gastric cancer. We aimed to identify the clinicopathological features and rate of lymph node metastasis (LNM) to investigate the feasibility of endoscopic submucosal dissection for early gastric LELC confined to the mucosa or submucosa. Methods: We compared the clinicopathological characteristics of 116 early gastric LELC patients and 5,753 early gastric well- or moderately differentiated (WD or MD) tubular adenocarcinoma patients treated by gastrectomy. Results: Compared to WD or MD early gastric cancer (EGC) patients, early LELC patients were younger and had a higher prevalence of proximally located tumors. Despite more frequent deep submucosal invasion (86.2% vs 29.8%), lymphatic invasion was less frequent (6.0% vs 16.2%) in early LELC patients than in WD or MD EGC patients. Among tumors with deep submucosal invasion, the tumor size was smaller, lymphatic invasion was less frequent (6.0% vs 40.2%) and the rate of LNM was lower (10.0% vs 19.4%) in patients with LELC than in those with WD or MD EGC. The overall rate of LNM in early LELC patients was 8.6% (10/116). The risk of LNM in patients with mucosal, shallow submucosal invasive, or deep submucosal invasive LELC was 0% (0/6), 0% (0/10), and 10% (10/100), respectively. Conclusions Early LELC is a distinct subtype of EGC with more frequent deep submucosal invasion but less lymphatic invasion and LNM than WD or MD EGCs. Endoscopic submucosal dissection may be considered curative for patients with early LELC confined to the mucosa or shallow submucosa, given its negligible rate of LNM.

Purpose: Foveolar-type adenocarcinoma of the stomach is a rare variant of gastric cancer.The clinicopathological features and outcomes of endoscopic submucosal dissection (ESD) for gastric foveolar-type adenocarcinoma remain unclear. Materials and Methods: This study included 1,161 patients who underwent ESD for single early gastric cancers (EGCs) (78 foveolar-type adenocarcinomas and 1,083 well-differentiated [WD] adenocarcinomas). The clinicopathological features and short- and long-term outcomes of ESD for gastric foveolar-type adenocarcinomas were reviewed and compared with those for WD EGCs. Results: Gastric foveolar-type adenocarcinomas were larger and more likely to exhibit an elevated macroscopic appearance than WD EGCs. Foveolar-type adenocarcinomas exhibited higher rates of lymphatic invasion, histological heterogeneity, and lateral margin involvement than WD EGCs. The en bloc R0 and curative resection rates of foveolar-type adenocarcinoma were 85.9% and 76.9%, respectively. Both foveolar-type adenocarcinoma rates were significantly lower than those of WD EGCs (95.8% and 91.3%, respectively). Lateral margin involvement accounted for 55.6% of the non-curative resection cases of foveolar-type adenocarcinoma.Among patients who underwent curative ESD for foveolar-type adenocarcinoma, no recurrence occurred during the median 62.3 months of follow-up. No lymph node metastases were detected in patients with foveolar-type adenocarcinoma who underwent additional surgery following ESD. The overall and disease-specific survival rates of patients with foveolar-type adenocarcinoma were comparable to those of patients with WD EGC. Conclusions Gastric foveolar-type adenocarcinomas have distinct clinicopathological features among WD EGCs. Given favorable long-term outcomes after curative resection, ESD can be indicated for early gastric foveolar-type adenocarcinomas.

Background: Despite the proven effectiveness of oral antivirals against severe acute respiratory syndrome coronavirus 2 in randomized trials, their clinical reevaluation is vital in the context of widespread immunity and milder prevalent variants. This study aimed to assess the effectiveness of oral antivirals for coronavirus disease 2019 (COVID-19). Methods: This retrospective cohort study utilized a target trial emulation framework to analyze patients with COVID-19 aged 60+ from January to December 2022. Data were obtained from the Korea Disease Control and Prevention Agency and Health Insurance Review and Assessment Service. The study involved 957,036 patients treated with nirmatrelvir/ritonavir and 243,360 treated with molnupiravir, each compared with the matched control groups. Primary outcome was progression to critical COVID-19 requiring advanced respiratory support. Secondary outcomes included progression to severe COVID-19, need for supplemental oxygen, and death within 30 days of the onset of COVID-19.Number needed to treat (NNT) derived from the absolute risk reduction. Results: Nirmatrelvir/ritonavir was significantly associated with a reduced risk of severe (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.803–0.843), critical (aOR, 0.560; 95% CI, 0.503–0.624), and fatal COVID-19 (aOR, 0.694; 95% CI, 0.647–0.744).Similarly, molnupiravir reduced the risk of severe (aOR, 0.895; 95% CI, 0.856–0.937), critical (aOR, 0.672; 95% CI, 0.559–0.807), and fatal cases (aOR, 0.679; 95% CI, 0.592–0.779).NNTs for nirmatrelvir/ritonavir were 203.71 (severe), 1,230.12 (critical), and 691.50 (death);for molnupiravir, they were 352.70 (severe), 1,398.62 (critical), and 862.98 (death). Higher effectiveness was associated with older adults, unvaccinated individuals, and the late pandemic phase. Conclusion Nirmatrelvir/ritonavir and molnupiravir are effective in preventing progression to severe disease in elderly adults with COVID-19.