Endoscopic Resection for Superficial Non-Ampullary Duodenal Epithelial Tumors.

An increasing number of superficial non-ampullary duodenal epithelial tumors (SNADETs) have been detected recently owing to the development of endoscopic imaging technology and increased awareness of this disease. Endoscopic resection is the first-line treatment for SNADETs, with methods including cold snare polypectomy (CSP), conventional endoscopic mucosal resection (cEMR), underwater EMR (uEMR), and endoscopic submucosal dissection (ESD). Here, we review the current status and recent advances in endoscopic resection for SNADETs. Endoscopic resection in the duodenum is more difficult and has a higher risk of adverse events than that in other organs owing to specific anatomical disadvantages. SNADETs ≤10 mm in size are candidates for CSP, cEMR, and uEMR. Among these lesions, suspected carcinoma lesions should not be treated using CSP because of their low curability. cEMR or uEMR is considered for lesions sized 10 to 20 mm, whereas piecemeal EMR or ESD is considered for tumors >20 mm in size. In particular, ESD or surgical resection should be considered for suspected carcinoma lesions >30 mm in size. The treatment plan should be selected on a case-to-case basis, considering the balance between the risk of adverse events and the necessity of en bloc resection.

Empirical Therapy Versus Tailored Therapy of Helicobacter pylori in Korea: Results of the K-CREATE Study.

BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.

Clinical Implications of Circulating Tumor Cells in Patients with Esophageal Squamous Cell Carcinoma: Cancer-Draining Blood Versus Peripheral Blood.

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.

Optimal Surveillance of Metachronous Gastric Lesion after Endoscopic Resection of Early Gastric Cancer.

Endoscopic resection (ER)-a minimal invasive procedure, compared to surgical gastrectomy, with the advantage of preserving the entire stomach and maintaining the patient's quality of life-is a widely used curative treatment for early gastric cancers (EGCs). Despite its advantages, such as the preservation of the whole stomach, a large area of the gastric mucosa with histologic changes such as atrophy and intestinal metaplasia remains after ER, and so does the risk of metachronous gastric cancers (MGCs). Therefore, regular surveillance endoscopy after curative ER of EGCs is important so that MGCs are detected early and so minimally invasive ER remains a treatment option. To date, the optimal interval for surveillance endoscopy after curative ER of EGCs has not been established. Therefore, this review summarizes the results of the published studies on this topic with the aim of establishing the optimal surveillance interval for early identification of MGCs. Based on my review, the median timing of MGC occurrence is within 3 years, and reports suggest biannual endoscopy during the first 3 years; however, the evidence suggests that individual patient characteristics may influence the risk of MGCs. Therefore, stratified endoscopic strategies for surveillance based on patient characteristics, such as age, family history of gastric cancer, synchronous gastric lesions, and corpus intestinal metaplasia, should be applied.

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.

Randomized, Double-Blind, Active-Controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan Compared With Esomeprazole in Erosive Esophagitis.

INTRODUCTION: Zastaprazan is a potent potassium-competitive acid blocker developed to treat gastroesophageal reflux disease. The aim of this study was to evaluate the efficacy and safety of zastaprazan compared with esomeprazole in patient with erosive esophagitis (EE). METHODS: A phase III, multicenter, randomized, double-blind, noninferiority 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 end point was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary end points 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 the 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 2 groups ( P = 0.047), but both decreased after treatment. DISCUSSION: An 8-week therapy of zastaprazan 20 mg is noninferior 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.

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.

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).