METHODS: We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded.
RESULTS: Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% [95% CI, -20.3% to -4.3%] and -13.3% [95% CI, -21.3% to -5.3%], respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group.
CONCLUSION: Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE.
TRIAL REGISTRATION: https://clinicaltrials.gov; NCT02388737.
DESIGN: A cross-sectional study on consecutive patients with dyspepsia undergoing upper gastrointestinal endoscopy.
SETTING: A large general hospital in Kuala Lumpur, Malaysia.
PARTICIPANTS: Consecutive patients undergoing endoscopy for upper abdominal discomfort were examined for the presence of reflux oesophagitis, hiatus hernia and Barrett's oesophagus. The diagnosis and classification of reflux oesophagitis was based on the Los Angeles classification. Patients with predominant symptoms of heartburn or acid regurgitation of at least one per month for the past 6 months in the absence of reflux oesophagitis were diagnosed as having NERD. The prevalence of GORD, reflux oesophagitis and NERD were analysed in relation to age, gender, race, body mass index (BMI), presence of hiatus hernia, Helicobacter pylori status, alcohol intake, smoking and level of education.
RESULTS: One thousand patients were studied prospectively. Three hundred and eighty-eight patients (38.8%) were diagnosed as having GORD based on either predominant symptoms of heartburn and acid regurgitation and/or findings of reflux oesophagitis. One hundred and thirty-four patients (13.4%) had endoscopic evidence of reflux oesophagitis. Two hundred and fifty-four (65.5%) were diagnosed as having NERD. Hiatus hernia was found in 6.7% and Barrett's oesophagus in 2% of patients. Of our patients with reflux oesophagitis 20.1% had grade C and D oesophagitis. No patients had strictures. Following logistic regression analysis, the independent risk factors for GORD were Indian race (odds ratio (OR), 3.25; 95% confidence interval (CI), 2.38-4.45), Malay race (OR, 1.67; 95% CI, 1.16-2.38), BMI > 25 (OR, 1.41; 95% CI, 1.04-1.92), presence of hiatus hernia (OR, 4.21; 95% CI, 2.41-7.36), alcohol consumption (OR, 2.42; 95% CI, 1.11-5.23) and high education level (OR, 1.52; 95% CI, 1.02-2.26). For reflux oesophagitis independent the risk factors male gender (OR, 1.64; 95% CI, 1.08-2.49), Indian race (OR, 3.25; 95% CI, 2.05-5.17), presence of hiatus hernia (OR, 11.67; 95% CI, 6.40-21.26) and alcohol consumption (OR, 3.22; 95% CI, 1.26-8.22). For NERD the independent risk factors were Indian race (OR, 3.45; 95% CI, 2.42-4.92), Malay race (OR, 1.80; 95% CI, 1.20-2.69), BMI > 25 (OR, 1.47; 95% CI, 1.04, 2.06) and high education level (OR, 1.66; 95% CI, 1.06-2.59).
CONCLUSIONS: Reflux oesophagitis and Barrett's oesophagus were not as uncommon as previously thought in a multiracial Asian population and a significant proportion of our patients had severe grades of reflux oesophagitis. NERD, however, still constituted the larger proportion of patients with GORD. Indian race was consistently a significant independent risk factor for reflux oesophagitis, NERD and for GORD overall.
AIM: To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists.
METHODS: Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis, surveillance and management of BE.
RESULTS: Five hundred sixty-nine of 1016 (56.0%) respondents completed the survey, with most respondents from Japan (n = 310, 54.5%) and China (n = 129, 22.7%). Overall, the preferred endoscopic landmark of the esophagogastric junction was squamo-columnar junction (42.0%). Distal palisade vessels was preferred in Japan (59.0% vs 10.0%, P < 0.001) while outside Japan, squamo-columnar junction was preferred (59.5% vs 27.4%, P < 0.001). Only 16.3% of respondents used Prague C and M criteria all the time. It was never used by 46.1% of Japanese, whereas 84.2% outside Japan, endoscopists used it to varying extents (P < 0.001). Most Asian endoscopists (70.8%) would survey long-segment BE without dysplasia every two years. Adherence to Seattle protocol was poor with only 6.3% always performing it. 73.2% of Japanese never did it, compared to 19.3% outside Japan (P < 0.001). The most preferred (74.0%) treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis. For BE with low-grade dysplasia, 6-monthly surveillance was preferred in 61.9% within Japan vs 47.9% outside Japan (P < 0.001).
CONCLUSION: Diagnosis and management of BE varied within Asia, with stark contrast between Japan and outside Japan. Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction, which is incorrect. Most also did not consistently use Prague criteria, and Seattle protocol. Lack of standardization, education and research are possible reasons.
DESIGN: In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs).
RESULTS: In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively.
CONCLUSION: Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms.
TRIAL REGISTRATION NUMBER: NCT02388724.
CASE PRESENTATION: A 30-year-old man was retrieved from the jungle with severe weight loss and abdominal symptoms. He succumbed to death despite 22 days of intensive medical treatment. An autopsy revealed a ruptured gangrenous ileal volvulus with peritonitis and subdiaphragmatic abscess. Further laboratory analysis detected systemic Candida tropicalis and intestinal gramnegative bacterial sepsis, systemic Zika virus viremia, leptospirosis complicating rhabdomyolysis and disseminated intravascular coagulopathy, Type I Herpes Simplex virus infection of the tongue and upper gastrointestinal tract. The cause of death was the ruptured ileal volvulus, complicated with upper gastrointestinal bleeding due to Herpes simplex virus esophagitis in a malnourished patient with resolving leptospirosis and underlying Zika virus co-infection.
CONCLUSION: Rare clinical scenarios of adult-onset intestinal volvulus with concomitant multiple infections precludes clinical diagnosis and early treatment, leading to devastating consequences of clinical outcome. The positive clinical and postmortem correlation is a good learning lesson in many disciplines of medicine and science.