Proton Pump Inhibitor Therapy before and after Endoscopic Submucosal Dissection: A Review

Abstract

Endoscopic submucosal dissection (ESD) is a novel endoscopic procedure first developed in the 1990s which enables en bloc resection of gastric neoplastic lesions that are difficult to resect via conventional endoscopic mucosal resection. However, given that ESD increases the risk of intra- and post-ESD delayed bleeding and that platelet aggregation and coagulation in artificial ulcers after ESD strongly depend on intragastric pH, faster and stronger acid inhibition via proton pump inhibitors (PPIs) and histamine 2-receptor antagonists (H(2)RAs) as well as endoscopic hemostasis by thermocoagulation during ESD have been used to prevent ESD-related bleeding. Because PPIs more potently inhibit acid secretion than H(2)RAs, they are often the first-line drugs employed in ESD treatment. However, acid inhibition after the initial infusion of a PPI is weaker in the early phase than that achievable with H(2)RAs; further, PPI effectiveness can vary depending on genetic differences in CYP2C19. Therefore, optimal acid inhibition may require tailored treatment based on CYP2C19 genotype when ESD is performed, with a concomitant infusion of PPI and H(2)RA possibly most effective for patients with the rapid metabolizer CYP2C19 genotype, while PPI alone may be sufficient for those with the intermediate or poor metabolizer genotypes.

Figure 1

Median 6 h pH-time profiles of intravenous infusions of placebo, famotidine, and omeprazole in a Western population model (CYP2C19 RM (n = 7), IM (n = 2), and PM (n = 1)) (a) and East-Asian population model (CYP2C19 RM (n = 3), IM (n = 5) and PM (n = 2)) (b).

Figure 2

Metabolic pathways of esomeprazole, omeprazole, lansoprazole, and rabeprazole in relation to cytochrome P450 isoenzymes CYP2C19 and CYP3A4. Weight of arrows indicates the relative contribution of the different enzyme pathways.

Figure 3

Plasma rabeprazole levels (a) and 24 h pH profiles (b) after rabeprazole 20 mg od treatment as a function of the CYP2C19 genotype group [58]. Abbreviations: RM, rapid extensive metabolizer; IM, intermediate extensive metabolizer; PM, poor metabolizer.

Figure 4

Median 12 h pH level in different intravenous infusion regimens (placebo, famotidine 20 mg, omeprazole 20 mg, famotidine 10 mg plus omeprazole 10 mg (half-concomitant), famotidine 20 mg plus omeprazole 20 mg (full-concomitant)) in CYP2C19 RM, IM, and PM genotype groups (a). Median 6-h pH-time profiles of intravenous infusions of famotidine alone, omeprazole alone, and a concomitant of famotidine and omeprazole in the RM (b), IM (c), and PM genotype groups (d). *P < 0.05 using the Wilcoxon's signed rank test, when significant differences were obtained by the Friedmann's test.