Introduction

The acid-suppressive drug such as proton pump inhibitor (PPI) is one of treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers(P-CABs) for treating FD is not established. This study aimed to assess the efficacy and safety of tegoprazan in patients with FD in a prospective, multicenter clinical trial.

Aims & Methods

Investigated FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50mg once daily for 8 weeks. Dyspeptic symptoms were assessed by a dyspepsia symptom questionnaire (5-point Likert scale, NDI-K, and GERD-HRQL). The main outcome was the rate of satisfactory relief of dyspeptic symptoms at 8weeks.

Results

A total of 173 patients were enrolled in this study. The rate of satisfactory relief of dyspeptic symptoms at 4 and 8weeks was 74.6% and 86.7%, respectively. The complete symptom relief rate at 4 and 8weeks was 15.0% and 24.9%, respectively. The symptom resolution rate was significantly higher at 8weeks than at 4weeks. (86.7% vs. 74.6%, p<0.001; 24.9% vs. 15.0%, p=0.003). The mean score of NDI-K and GERD-HRQL also significant decreased at 8weeks. The efficacy was not influenced by subtypes of FD or Helicobacter pylori status. There was no serious adverse event or death during the study.

Conclusion

Tegoprazan 50mg once daily significantly provides satisfactory symptom relief for FD. (International clinical trial registry number: KCT0005600)

Introduction

Fexuprazan, a novel potassium-competitive acid blocker (P-CAB), is currently recognized as a successful alternative to proton pump inhibitors (PPIs) for acid-related disorders. However, its experience in the global market remains limited.

Aims & Methods

This study aimed to integrate two randomized phase 3 studies (NCT03736369 in South Korea and NCT05813561 in China) investigating the efficacy and safety of fexuprazan in subjects with erosive esophagitis (EE) across Asian populations, especially those with at least moderate severity of major symptoms (≥2 days of heartburn or acid regurgitation at baseline). The Cochran-Mantel-Haenszel method was used to assess the efficacy of fexuprazan 40 mg and esomeprazole 40 mg in treating EE and relieving major symptoms, whereas the Wilcoxon signed-rank test evaluated safety by testing changes in gastrin levels within each treatment group.

Results

Of the 595 randomized subjects, 513 (256 in the fexuprazan group and 257 in the esomeprazole group) were included in the efficacy analysis set (per-protocol set, PPS). In the PPS, the healing rates of EE in the fexuprazan and esomeprazole groups at weeks 4 and 8 were 86.90% and 84.00% (95% confidence interval [CI] = -2.80, 9.23) and 98.05% and 98.44% (95% CI = -2.30, 2.02), respectively. In the subgroup analysis of patients with at least a moderate severity of major symptoms (205 in the fexuprazan group and 197 in the esomeprazole group), the healing rates of EE did not differ between the two groups (week 4, 85.57% vs. 83.33% [95% CI = -4.70, 9.28]; week 8, 97.56% vs. 97.97% [95% CI = -2.84, 2.61]). However, the proportion of subjects without symptoms in the first 3 days in both full day and nighttime in the fexuprazan group was significantly higher than that in the esomeprazole group (20.44% vs. 11.90%, p = 0.0212 and 32.04% vs. 22.02%, p = 0.0387, respectively). In the safety set, serum gastrin levels at the final visit significantly increased by 87.23 pg/ml and 61.99 pg/ml from baseline serum gastrin levels in both fexuprazan and esomeprazole groups, respectively. However, the mean gastrin levels at the final visit in both groups did not increase to the clinically significant levels (121.89 pg/ml vs. 96.40 pg/ml, respectively). None of the observed increases in gastrin levels resulted in discontinuation of the study, and no significant safety risks were identified in either group.

Conclusion

The efficacy of fexuprazan in treating EE was not inferior to that of esomeprazole in Asian populations. In subjects with at least a moderate severity of major symptoms, symptom relief in the fexuprazan group was higher in the first 3 days, regardless of full-day or nighttime. In terms of safety, serum gastrin level was tolerable in both groups, and no serious adverse events occurred in the fexuprazan group.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is frequently indicated in patients who underwent Roux-en-Y gastric bypass (RYGB) surgery. (1, 2) However, due to the altered anatomy, it is challenging to gain pancreatobiliary access in patients following a RYGB. Several strategies are currently available, but all have their disadvantages. Laparoscopy-assisted ERCP (LA-ERCP), the current golden standard, has higher success rates but also comes with logistical challenges of intraoperative ERCP, peri-operative complications and high costs. (3 - 5) Endoscopic ultrasound directed ERCP (EDGE) is a technique used to create a gastro-gastrostomy by placing a lumen apposing metal stent (LAMS) between the gastric pouch and the excluded stomach, facilitating subsequent ERCP.(6) Although EDGE gained more popularity over the last few years, prospective studies are lacking.

Aims & Methods

The aim of this study is to provide prospective evidence for the efficacy and safety of EDGE, including fistula closure.This multicentre prospective cohort study included all consecutive patients scheduled for elective ERCP after RYGB surgery. EDGE was performed as a two-step procedure. Primary endpoint was overall technical success. Secondary endpoints were technical success of LAMS placement and ERCP individually, persistent fistula and other procedure-related adverse events (AEs).

Results

Between January 2021 and August 2024, 26 patients were included in 4 Dutch hospitals. Overall technical success was achieved in 25/26 patients (96.2%). Median LAMS indwelling time was 14 days [IQR 11 – 28 days]. Two EDGE-related AEs occurred (7.7%); one perforation of the contralateral duodenal wall following scope insertion and one bleeding after LAMS placement. Two ERCP-related AEs occurred (7.7%): one CBD perforation and one post-ERCP pancreatitis. Two patients were lost to follow-up. None of the remaining patients had a persistent fistula, based on radiologic or endoscopic evidence (0/24). No mortality occurred.

Conclusion

This prospective study shows that two-step EDGE is relatively safe and associated with high technical success, without any cases of a persistent fistula. However, AEs occurred in 4 patients (15.4%), of which two were EDGE-related (7.7%).

References

1. Yang H, Petersen GM, Roth MP, Schoenfield LJ. Risk factors for gallstone formation during rapid loss of weight. Digestive diseases and sciences. 1992;37(6):912-8.
2. Haal S, Guman MSS, Boerlage TCC, Acherman YIZ, de Brauw LM, Bruin S, et al. Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial. Lancet Gastroenterol Hepatol. 2021;6(12):993-1001.
3. Gangwani MK, Aziz M, Haghbin H, Iqbal A, Dillard J, Dahiya DS, et al. Comparing EUS-directed Transgastric ERCP (EDGE) Versus Laparoscopic-Assisted ERCP Versus Enteroscopic ERCP: A Network Meta-analysis. J Clin Gastroenterol. 2024;58(2):110-9.
4. da Ponte-Neto AM, Bernardo WM, de ACLM, Josino IR, Brunaldi VO, Moura DTH, et al. Comparison between Enteroscopy-Based and Laparoscopy-Assisted ERCP for Accessing the Biliary Tree in Patients with Roux-en-Y Gastric Bypass: Systematic Review and Meta-analysis. Obes Surg. 2018;28(12):4064-76.
5. Abbas AM, Strong AT, Diehl DL, Brauer BC, Lee IH, Burbridge R, et al. Multicenter evaluation of the clinical utility of laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass. Gastrointestinal endoscopy. 2018;87(4):1031-9.
6. van Wanrooij RLJ, Bronswijk M, Kunda R, Everett SM, Lakhtakia S, Rimbas M, et al. Therapeutic endoscopic ultrasound: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review. Endoscopy. 2022;54(3):310-32.

Clinical Case Summary

A 71-year-old female presented to the gastroenterology clinic following a two year history of dysphagia and sensation of food sticking in the oesophagus. Her dysphagia was limited to solid foods, and symptoms were not exacerbated by positional change. Pain was mostly localised around the sternal notch where she would have the sensation of a food bolus. Over the preceding 2 years, she had experienced about 7.5kg of weight loss with no constitutional symptoms of fevers or fatigue. Her past medical history included hypertension, dyslipidaemia, lower back pain, cold agglutinin disease, monoclonal B lymphocytosis and peripheral arterial disease. On examination, there were no signs of malnourishment or palpable lymph nodes in the axilla, neck or supraclavicular region. Her abdomen was soft and non-tender. Given largely non-illuminating blood results, an oesophageal-gastroduedonoscopy was performed. However, no findings were noted, specifically no oesophageal webs, Zenker diverticulum, gastroparesis, trachealisation of the oesophagus or corrosive pathology. H. pylori was also not isolated on histopathology. A barium swallow was then performed which showed extensive external compression of the proximal third of the oesophagus at the level of the arch of the aorta, most indicative of dysphagia lusoria (Fig 1). Computed tomography angiography (CTA) showed retroesophageal aberrant right subclavian artery bifurcating from the ascending aorta independent of a brachiocephalic artery and causing external oesophageal compression (Fig 2 & 3). Given this definitive diagnosis, the patient was then seen in clinic where management of dysphagia lusoria was explained. Despite ongoing symptoms, the patient decided to continue with conservative management and lifestyle modifications, which included eating smaller bites and increase in fluid intake. Although an extensive compression typically requires surgical intervention, our patient was stable at two-year follow-up (Fig 4 A-B).

References

Figure 1: Barium swallow examination showing extrinsic compression of the proximal third of the oesophagus at the level of the aortic arch (white arrow).
Figure 2: Axial view of computed tomography angiography (CTA) showing the posterior course of the retroesophageal aberrant right subclavian artery.
Figure 3: Axial view of computed tomography angiography (CTA) showing compression of oesophagus (white arrow) by the retroesophageal aberrant right subclavian artery (white arrowhead).
Figure 4: Computed tomography angiography (CTA) multi-planar reconstruction (MPR) showing the posterior course of the right subclavian artery (white arrow), crossing the mediastinum and compressing the oesophagus. A. coronal view B. Sagittal view

Disclosure

None.