Concerns have been raised regarding the long-term use of proton pump inhibitors (PPIs) as an important risk factor for gastric cancer in clinical practice. PPIs can cause hypergastrinemia at clinical doses, and hypergastrinemia has been reported to induce malignant neoplasms in the stomach in previous animal studies. In humans, the proliferation of enterochromaffin-like (ECL) cells induced by hypergastrinemia is suspected as a potential mechanism of gastric cancer. Meanwhile, persistent Helicobacter pylori (H. pylori) infection causes gastric atrophic change, which itself is a major cause of gastric cancer, and it can further increase the risk of gastric cancer by strengthening corpus atrophy through interaction with PPIs. Recent epidemiologic studies have reported an important link between long-term PPI intake and gastric cancer risk even after successful eradication of H. pylori. However, due to the methodological limitations of observational clinical studies, the causal relationship is still not clear, and a recent big data-based study reported that long-term PPI use was not related to gastric cancer incidence. Taken together, despite the potential detrimental effects of PPIs, it is currently difficult to draw a definite conclusion about its association with gastric cancer. To minimize the possibility of gastric cancer in H. pylori-infected patients or precancerous lesions in long-term PPI users, long-term PPI administration should be limited to the minimum effective dose, and antibacterial treatment for H. pylori should be considered.

Concerns have been raised regarding the long-term use of proton pump inhibitors (PPIs) as an important risk factor for gastric cancer in clinical practice. PPIs can cause hypergastrinemia at clinical doses, and hypergastrinemia has been reported to induce malignant neoplasms in the stomach in previous animal studies. In humans, the proliferation of enterochromaffin-like (ECL) cells induced by hypergastrinemia is suspected as a potential mechanism of gastric cancer. Meanwhile, persistent Helicobacter pylori (H. pylori) infection causes gastric atrophic change, which itself is a major cause of gastric cancer, and it can further increase the risk of gastric cancer by strengthening corpus atrophy through interaction with PPIs. Recent epidemiologic studies have reported an important link between long-term PPI intake and gastric cancer risk even after successful eradication of H. pylori. However, due to the methodological limitations of observational clinical studies, the causal relationship is still not clear, and a recent big data-based study reported that long-term PPI use was not related to gastric cancer incidence. Taken together, despite the potential detrimental effects of PPIs, it is currently difficult to draw a definite conclusion about its association with gastric cancer. To minimize the possibility of gastric cancer in H. pylori-infected patients or precancerous lesions in long-term PPI users, long-term PPI administration should be limited to the minimum effective dose, and antibacterial treatment for H. pylori should be considered.

Purpose: As the rate of endoscopic resection for early gastric cancer (EGC) has increased in patients with comorbid diseases, it is necessary to elucidate the efficacy of endoscopic submucosal dissection (ESD) for EGC in patients with comorbidities. This study aimed to analyze the clinical outcomes of ESD for EGC in patients with comorbidities. Materials and Methods: A total of 969 patients with 1,015 lesions who underwent ESD for EGC at Seoul National University Hospital between 2010 and 2014 were analyzed. The shortand long-term clinical outcomes were evaluated according to the comorbidity status. Results: Comorbidities were observed in 558 patients (57.6%). The comorbidity group had a higher proportion of patients using antithrombotic agents (29.5% vs. 0.9%; P<0.0001).Although procedure-related complications (bleeding and perforation) were not significantly different between the two groups, the length of hospital stay was significantly longer (1.8 vs.1.4 days, P=0.023), while survival was significantly shorter in the comorbidity group (5-year overall survival rate: 90.5% vs. 97.2%, P<0.0001; 5-year disease-specific survival rate: 97.9% vs. 100%, P=0.018; 5-year disease-free survival rate: 83.4% vs. 89.2%, P=0.007). Conclusions Gastric ESD can be performed in patients with comorbidities without increasing the risk of complications.

Background: This study aimed to identify the effect of histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) use on the positivity rate and clinical outcomes of coronavirus disease 2019 (COVID-19). Methods: We performed a nationwide cohort study with propensity score matching using medical claims data and general health examination results from the Korean National Health Insurance Service. Individuals aged ≥ 20 years who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 January and 4 June 2020 were included.Patients who were prescribed H2RA or PPI within 1 year of the test date were defined as H2RA and PPI users, respectively. The primary outcome was SARS-CoV-2 test positivity, and the secondary outcome was the instance of severe clinical outcomes of COVID-19, including death, intensive care unit admission, and mechanical ventilation administration. Results: Among 59,094 patients tested for SARS-CoV-2, 21,711 were H2RA users, 12,426 were PPI users, and 24,957 were non-users. After propensity score matching, risk of SARS-CoV-2 infection was significantly lower in H2RA users (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.74–0.98) and PPI users (OR, 0.62; 95% CI, 0.52–0.74) compared to non-users. In patients with comorbidities including diabetes, dyslipidemia, and hypertension, the effect of H2RA and PPI against SARS-CoV-2 infection was not significant, whereas the protective effect was maintained in patients without such comorbidities. Risk of severe clinical outcomes in COVID-19 patients showed no difference between users and non-users after propensity score matching either in H2RA users (OR, 0.89; 95% CI, 0.52–1.54) or PPI users (OR, 1.22; 95% CI, 0.60–2.51). Conclusion H2RA and PPI use is associated with a decreased risk for SARS-CoV-2 infection but does not affect clinical outcome. Comorbidities including diabetes, hypertension, and dyslipidemia seem to offset the protective effect of H2RA and PPI.