Efficacy of fexuprazan compared with rebamipide in Korean patients with gastritis: A matching-adjusted indirect comparison.

BACKGROUND: Gastritis is one of the most frequently diagnosed diseases requiring medical treatment in South Korea. Fexuprazan, a novel potassium-competitive acid blocker, has been approved for treating gastritis and erosive esophagitis. Meanwhile, rebamipide is the most commonly used mucoprotective agent for acute and chronic gastritis in real-world settings in South Korea. However, there have been no studies comparing the efficacy of these two drugs yet. AIM: To compare the efficacy of fexuprazan with that of rebamipide for acute and chronic gastritis. METHODS: This was a matching-adjusted indirect comparison. Individual patient data from a phase III study of fexuprazan (10 mg BID) were compared with cumulative data from two matching studies of rebamipide (100 mg TID). Erosion improvement and healing rates were compared between two weeks of fexurapan, two weeks of rebamipide, and four weeks of rebamipide. The two main outcome variables were presented as percentages, and the risk differences (RD) and 95% confidence intervals (CI) were calculated for the relative treatment effects. RESULTS: In the primary analysis, the erosion improvement and healing rates after a two-week treatment with fexuprazan were 64.5% and 53.2%, respectively, while a two-week treatment with rebamipide resulted in erosion improvement and healing rates of 43.6% (RD: 21.0%; 95%CI: 9.6-32.3; P < 0.01) and 35.6% (RD: 17.6%; 95%CI: 6.1-29.2; P = 0.003), respectively. In the additional analysis, the erosion improvement and healing rates for the two-week fexuprazan treatment (64.2% and 51.2%, respectively) were similar to those obtained during a four-week treatment with rebamipide (60.6%; RD: 3.6%; 95%CI: -9.8, 17.0; P = 0.600 and 53.5%; RD: -2.3%; 95%CI: -16.1, 11.5; P = 0.744, respectively). CONCLUSION: The two-week fexuprazan treatment was superior to the two-week rebamipide treatment and similar to the four-week rebamipide treatment for patients with gastritis.

Artificial Intelligence-Based Diagnosis of Gastric Mesenchymal Tumors Using Digital Endosonography Image Analysis.

Background/Objectives: Artificial intelligence (AI)-assisted endoscopic ultrasonography (EUS) diagnostic tools have shown excellent performance in diagnosing gastric mesenchymal tumors. This study aimed to assess whether incorporating clinical and endoscopic factors into AI-assisted EUS classification models based on digital image analysis could improve the diagnostic performance of AI-assisted EUS diagnostic tools. Methods: We retrospectively analyzed the data of 464 patients who underwent both EUS and surgical resection of gastric mesenchymal tumors, including 294 gastrointestinal stromal tumors (GISTs), 52 leiomyomas, and 41 schwannomas. AI-assisted classification models for GISTs and non-GIST tumors were developed utilizing clinical and endoscopic factors and digital EUS image analysis. Results: Regarding the baseline EUS classification models, the area under the receiver operating characteristic (AUC) values of the logistic regression, decision tree, random forest, K-nearest neighbor (KNN), and support vector machine (SVM) models were 0.805, 0.673, 0.781, 0.740, and 0.791, respectively. Using the new classification models incorporating clinical and endoscopic factors into the baseline classification models, the AUC values of the logistic regression, decision tree, random forest, KNN, and SVM models increased to 0.853, 0.715, 0.896, 0.825, and 0.794, respectively. In particular, the random forest and KNN models exhibited significant improvement in performance in Delong's test (both p < 0.001). Conclusion: The diagnostic performance of the AI-assisted EUS classification models improved when clinical and endoscopic factors were incorporated. Our results provided direction for developing new AI-assisted EUS models for gastric mesenchymal tumors.

Randomized, Double-blind, Active-controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan compared to Esomeprazole in Erosive Esophagitis.

INTRODUCTION: Zastaprazan is a potent potassium-competitive acid blocker (P-CAB) developed to treat gastroesophageal reflux disease. This study aims to evaluate the efficacy and safety of zastaprazan compared to esomeprazole in patient with erosive esophagitis (EE). METHODS: A phase III, multicenter, randomized, double-blind, non-inferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary endpoint was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate at week 4, symptom response and quality of life assessment. Safety profiles and serum gastrin levels were also assessed. RESULTS: In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) (P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than esomeprazole group (95.14% (137/144) vs. 87.68% (121/138); P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the two groups (P = 0.047), but both decreased after treatment. DISCUSSION: An 8-week therapy of zastaprazan 20 mg is non-inferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

Effective Endoscopic Submucosal Dissection of a Huge Esophageal Liposarcoma: A Case Report.

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.

A rare case of esophageal mucoepidermoid carcinoma successfully treated via endoscopic submucosal dissection.

Esophageal mucoepidermoid carcinoma (EMEC) is a special subtype of esophageal malignancy, accounting for less than 1% of all cases of primary esophageal carcinoma. Pathologically, it consists of a mixture of adenocarcinoma and squamous cell carcinoma with mucin-secreting cells. Special staining for mucicarmine helps to diagnose EMEC. We present a rare case of EMEC successfully treated via endoscopic submucosal dissection (ESD). A 63-year-old man was referred to our tertiary hospital. On esophagogastroduodenoscopy, a 6-mm-sized subtle reddish depressed lesion was identified in the mid-esophagus. Diagnostic ESD was performed with a high suspicion of carcinoma. Histopathologic findings were consistent with EMEC which was confined to the lamina propria without lymphatic invasion. We plan to do a careful follow-up without administering adjuvant chemotherapy or radiotherapy. Due to the small volume of the lesion, establishing a diagnosis was difficult through forceps biopsy alone. However, by using ESD, we could confirm and successfully treat a rare case of early-stage EMEC.

A Modified eCura System to Stratify the Risk of Lymph Node Metastasis in Undifferentiated-Type Early Gastric Cancer After Endoscopic Resection.

PURPOSE: The original eCura system was designed to stratify the risk of lymph node metastasis (LNM) after endoscopic resection (ER) in patients with early gastric cancer (EGC). We assessed the effectiveness of a modified eCura system for reflecting the characteristics of undifferentiated-type (UD)-EGC. MATERIALS AND METHODS: Six hundred thirty-four patients who underwent non-curative ER for UD-EGC and received either additional surgery (radical surgery group; n=270) or no further treatment (no additional treatment group; n=364) from 18 institutions between 2005 and 2015 were retrospectively included in this study. The eCuraU system assigned 1 point each for tumors >20 mm in size, ulceration, positive vertical margin, and submucosal invasion <500 µm; 2 points for submucosal invasion ≥500 µm; and 3 points for lymphovascular invasion. RESULTS: LNM rates in the radical surgery group were 1.1%, 5.4%, and 13.3% for the low- (0-1 point), intermediate- (2-3 points), and high-risk (4-8 points), respectively (P-for-trend<0.001). The eCuraU system showed a significantly higher probability of identifying patients with LNM as high-risk than the eCura system (66.7% vs. 22.2%; McNemar P<0.001). In the no additional treatment group, overall survival (93.4%, 87.2%, and 67.6% at 5 years) and cancer-specific survival (99.6%, 98.9%, and 92.9% at 5 years) differed significantly among the low-, intermediate-, and high-risk categories, respectively (both P<0.001). In the high-risk category, surgery outperformed no treatment in terms of overall mortality (hazard ratio, 3.26; P=0.015). CONCLUSIONS: The eCuraU system stratified the risk of LNM in patients with UD-EGC after ER. It is strongly recommended that high-risk patients undergo additional surgery.

A Case of Esophageal MALT Lymphoma Mimicking a Subepithelial Tumor.

Mucosa-associated lymphoid tissue (MALT) lymphoma, also known as extranodal marginal zone lymphoma, is a low-grade B-cell lymphoma that can develop in the mucosal layer of various organs, including the gastrointestinal tract, salivary glands, lungs, and skin. The most common site is the gastrointestinal tract, particularly the stomach. On the other hand, primary esophageal lymphomas are extremely rare. MALT lymphomas can undergo histological transformation into more aggressive B-cell lymphomas, such as diffuse large B-cell lymphoma, resulting in a poor prognosis. This paper reports a rare case of primary esophageal MALT lymphoma mimicking a subepithelial tumor located in the lower esophagus that was treated successfully with radiotherapy. MALT lymphoma should be included in a differential diagnosis when subepithelial tumors are found in the esophagus, particularly if endoscopic ultrasonography reveals the tumor to be located in the deep mucosal and submucosal layers. Following the precise diagnosis, accurate staging and appropriate treatment are crucial. Regular follow-up is necessary to assess the possibility of recurrence or transformation to high-grade lymphoma.

The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study.

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.

Real-World Risk of Gastrointestinal Bleeding for Direct Oral Anticoagulants and Warfarin Users: A Distributed Network Analysis Using a Common Data Model.

Background/Aims: : Early studies on direct oral anticoagulants (DOACs) reported a higher risk of gastrointestinal bleeding (GIB) compared with warfarin; however, recent studies have reported a reduced risk. Therefore, this study was designed to evaluate the risk of GIB in users of DOAC and warfarin. Methods: : Using a common data model, we investigated the comparative risk of GIB in subjects from eight hospitals who were newly prescribed DOACs or warfarin. We excluded subjects who had a prior history of GIB or had been prescribed both medications. After propensity score matching, we analyzed 3,347 matched pairs of new DOAC and new warfarin users. Results: : The risk of GIB in new DOAC users was comparable to that in new warfarin users (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.65 to 1.40; p=0.808). New DOAC users had a similar risk of GIB to new warfarin users among older patients >65 years (HR, 1.00; 95% CI, 0.69 to 1.52; p=0.997) and in older patients >75 years (HR, 1.21; 95% CI, 0.68 to 2.10; p=0.509). In addition, the risk of GIB was not significantly different between two groups according to sex. We also found that the risk of GIB in DOAC users was 26% lower in edoxaban or apixaban subgroups compared to rivaroxaban or dabigatran subgroups (HR, 0.74; 95% CI, 0.69 to 1.00; p=0.049). Conclusions: : In real-world practice, the risk of GIB in new DOAC users is comparable to that in new warfarin users. In DOAC users, the risk of GIB was lower in edoxaban or apixaban subgroups than rivaroxaban or dabigatran subgroups.

Evaluation of the Efficacy and Safety of DW1903 in Patients with Gastritis: A Randomized, Double-Blind, Noninferiority, Multicenter, Phase 3 study.

Background/Aims: H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA. However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis. Methods: A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared. Results: According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different. Conclusions: DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).

Endoscopic submucosal dissection for early gastric cancer: It is time to consider the quality of its outcomes.

Endoscopic resection, particularly endoscopic submucosal dissection (ESD), is widely used as a standard treatment modality for early gastric cancer (EGC) when the risk of lymph node metastasis is negligible. Compared with surgical gastrectomy, ESD is a minimally invasive procedure with additional advantages, such as preservation of the entire stomach and maintenance of the patient's quality of life. However, not all patients achieve curative resection after ESD of EGC. Several patients require surgical gastrectomy after ESD to achieve a curative treatment. Additional surgery after ESD, owing to non-curative resection, places considerable emotional and financial burdens on patients. Recently, as the number of endoscopists performing ESD has increased, the rate of non-curative resection after ESD has increased correspondingly. In order to decrease the non-curative resection rate, as well as determine the ideal rate of non-curative resection after ESD, it is time to consider quality indicators for the outcomes of ESD for EGC.

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

A Gastric Magnetic Foreign Body Incidentally Detected Several Years after Ingestion.

Foreign body ingestion is commonly seen in children. However, occasionally it may also be seen among adults and is often associated with intellectual disability, psychiatric disorders, and alcoholism. Ingestion of a magnetic foreign body may cause complications such as gastrointestinal tract perforation, wherein emergency endoscopic removal of the foreign body is generally required. Here, we report a rare case of a 59-year-old male with an intellectual disability and psychiatric disorder in whom metallic objects in the stomach cavity were accidentally discovered during abdominal CT. Esophagogastroduodenoscopy revealed several metallic objects attached to two magnets, which had been ingested several years before and had remained in the stomach cavity. The magnets and metallic objects were safely removed endoscopically using rat-tooth forceps without complications.

Efficacy of Tegoprazan in Patients with Laryngopharyngeal Reflux Disease: A Preliminary Feasibility Study.

Tegoprazan is a novel, potent, and highly selective potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset of action and prolonged control of gastric acidity. We performed a preliminary feasibility study to evaluate whether tegoprazan could control symptoms more effectively than a placebo in patients with laryngopharyngeal reflux disease (LPRD). In this double-blind, randomized, placebo-controlled trial, 35 patients with LPRD were randomly assigned to two groups: tegoprazan 50 mg daily and placebo. The primary endpoint was the complete resolution rate of LPRD symptoms after 8 weeks of medication, and the secondary endpoints were the complete resolution rate of LPRD symptoms after 4 weeks of medication and changes in the reflux symptom index (RSI) and reflux finding score (RFS) from baseline at 4 and 8 weeks of medication. There was no difference in the complete symptom resolution rates at 8 weeks between the tegoprazan and placebo groups (29.4% [5/17] vs. 27.8% [5/18], p = 1.000). Moreover, there was no significant difference in the complete symptom resolution rates at 4 weeks between the two groups. Compared with the baseline, both tegoprazan and placebo significantly reduced the total RSI and RFS scores after 4 and 8 weeks of medication; however, tegoprazan was not superior to the placebo. In conclusion, tegoprazan (50 mg daily) administration improved LPRD symptoms and signs. However, tegoprazan did not show superiority over placebo. Considering the potential effectiveness of tegoprazan as an acid-suppressing therapy and the possibility of type II error due to a low number of included patients herein, prospective, large-scale, multi-center studies with a higher dose of tegoprazan for a prolonged duration are required to elucidate the efficacy of tegoprazan in patients with LPRD. (ClinicalTrials.gov: NCT05871398).

Long-term outcomes of endoscopic resection for duodenal neuroendocrine tumors.

Duodenal neuroendocrine tumors (d-NETs) ≤ 10 mm in size, confined to the submucosal layer, without lymph node or distant metastasis, can be treated safely and effectively by endoscopic management. However, most results are based on limited data and short follow-up outcomes. Herein, we aimed to evaluate the short-term and long-term outcomes of endoscopic resection for d-NETs. We retrospectively analyzed 63 patients with 68 d-NETs who had undergone endoscopic resection at two hospitals between January 2009 and December 2021. En-bloc resection, endoscopically complete resection, and histopathologically complete resection rates were evaluated as short-term outcomes. Furthermore, long-term outcomes were analyzed in 46 patients with 50 d-NETs with a follow-up period of > 1 year. The overall en-bloc, endoscopically complete, and histopathologically complete resection rates were 92.6% (63/68), 100% (68/68), and 69.1% (47/68), respectively. Tumor size (> 5 mm) was the only predictive factor for histopathologically incomplete resection (p = 0.015). The procedure-related bleeding and perforation rates were 0% and 5.9%, respectively. No recurrences were observed in patients with histopathologically complete resection and those with histopathologically incomplete resection at a median follow-up period of 48 months (range 12-132 months). Endoscopic resection for d-NETs ≤ 10 mm in size, limited to the submucosal layer, and without lymph node or distant metastasis provides favorable long-term outcomes when endoscopically complete resection is achieved.