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CYP2C19 genotype variability in patients with refractory gastroesophageal reflux after per-oral endoscopic myotomy (POEM).

ABSTRACT: Background and study aims Symptomatic gastroesophageal reflux is a recognized potential adverse event following peroral endoscopic myotomy (POEM). Proton pump inhibitors (PPIs) are an effective first-line therapy; although their efficacy can be affected by genotype cytochrome P450 2C19 (CYP2C19) variability leading to enhanced clearance of PPIs. The aim of our study was to evaluate the incidence of CYP2C19 genotype variability in POEM patients with refractory gastroesophageal reflux symptoms. Patients and methods This was a single-center, prospective, cohort study of consecutive POEM cases during a 7-year study period (2013-2020). Reflux symptoms were assessed with the validated gastroesophageal reflux disease questionnaire (GerdQ) and objective pH testing after POEM. CYP2C19 genotype testing was obtained in all patients with refractory gastroesophageal reflux disease (GERD) symptoms, defined as an abnormal pH study and GerdQ score ≥ 8 while on PPIs twice daily. Results POEM was performed in 325 consecutive patients (48.3 % female; mean age 57 years) during the study period. Twenty patients (6.8 %) had PPI-refractory, post-POEM gastroesophageal reflux based on their GerdQ score (median 9, range 8-11) and abnormal pH studies. CYP2C19 genotype testing identified 55 % (11/20) of these patients as being rapid metabolizers. Out of these, 9 (82 %) had improvement in clinical GERD symptoms after changing to a PPI less affected by CYP2C19 pharmacogenetics. Conclusions Post-POEM, PPI-refractory GERD is rare. As shown in this study, rapid metabolizers commonly respond by changing to a PPI less affected by CYP2C19 pharmacogenetics, thereby reducing the risk of long-term consequences from GERD and unnecessary anti-reflux surgery.

SUBMITTER: Perbtani YB

PROVIDER: S-EPMC8159581 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionPeroral endoscopic myotomy (POEM) is the standard treatment for achalasia. Functional luminal imaging probe (FLIP) technology enables objective measurement of lower esophageal sphincter (LES) geometry, with literature linking specific values to improved post-POEM outcomes. Our study assesses FLIP's intraoperative use in evaluating myotomy extent in real-time.MethodsRetrospective data from all patients undergoing POEM with intraoperative FLIP measurements were extracted from June 2020 to January 2023. The primary endpoint was intraoperative FLIP measurements, management changes, and symptom improvement (Eckardt score).ResultsFourteen patients (age 56 ± 14 years, BMI 28 ± 7 kg/m2) were identified. Most patients were female (64%). Predominantly, patients presented with type II achalasia (50%). FLIP measurements were taken before and after myotomy, demonstrating increases in mean distensibility index (DI) 1.6 ± 1. 4 to 5.4 ± 2.1 mm2/mmHg (p < 0.05) and mean diameter (Dmin) 6 ± 1.8 to 10.9 ± 2.3 mm (p < 0.05) at 50 ml balloon fill. Additional myotomy was performed in one patient when an inadequate increase in FLIP values were noted. Mean operative time was 98 ± 28 min, and there were no intraoperative complications. At the 30-day follow-up, median Eckardt score decreased from mean a preoperative score of 7 ± 2 to a post-operative mean of 2 ± 3, with 10 patients (78%) having a score ≤ 2. In total, four patients experienced symptom recurrence, with repeat FLIP values revealing a significant decrease in DI from 7 ± 2.2 post-POEM to 2.5 ± 1.5 at recurrence. FLIP technology identified LES pathology in 3 out of 4 (75%) patients, facilitating referral to LES-directed therapy.ConclusionOur study adds to the literature supporting the use of FLIP technology during the POEM procedure, with most patients achieving ideal values after a standard-length myotomy. This suggests the potential benefits of shorter myotomies guided by FLIP to achieve comparable outcomes and reduce postoperative GERD risk. Collaborative standardization of study designs and outcome measures is crucial for facilitating prospective trials and cross-setting outcome comparisons.

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CYP2C19 genotype variability in patients with refractory gastroesophageal reflux after per-oral endoscopic myotomy (POEM).

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