Esophagus/Reflux, in full.

In patients with classic GERD symptoms (heartburn, regurgitation) and no alarm symptoms, give an 8-week trial of empiric PPI ONCE DAILY before a meal (strong, moderate evidence); administer PPI 30-60 minutes before a meal rather than at bedtime (strong, moderate). Endoscopy is the FIRST test in patients presenting with dysphagia or other alarm symptoms, the guideline names weight loss and GI bleeding, and also in patients with multiple risk factors for Barrett's esophagus (strong, low). If classic symptoms respond to the 8-week trial, attempt to discontinue the PPI (conditional, low); for patients without erosive esophagitis or Barrett's whose symptoms resolved, an attempt at discontinuation should be made; patients requiring maintenance should take the lowest effective dose. If symptoms do not respond adequately to the 8-week trial, or return on discontinuation, perform diagnostic endoscopy, ideally after PPIs are stopped for 2-4 weeks (strong, low). Where GERD is suspected but unclear and endoscopy shows no objective evidence, perform reflux monitoring OFF therapy to establish the diagnosis (strong, low); conversely, do NOT perform off-therapy reflux monitoring solely as a diagnostic test in patients already known to have LA grade C or D esophagitis or long-segment Barrett's, because the diagnosis is already established (strong, low). In refractory GERD, optimize PPI therapy first (strong, moderate); then pH monitoring OFF PPIs if GERD was not previously established by pH study, long-segment Barrett's, or LA grade C/D esophagitis, versus impedance-pH ON PPIs where GERD is already established but symptoms persist on twice-daily PPI (both conditional, low). Before antireflux surgery or endoscopic therapy, HRM is recommended to rule out achalasia and absent contractility, with provocative testing (e.g., multiple rapid swallows) to identify contractile reserve in ineffective esophageal motility; on-therapy reflux monitoring is suggested before intervention in patients with prior objective GERD findings who remain symptomatic. Antireflux surgery by an experienced surgeon is an option for patients with OBJECTIVE evidence of GERD, with severe esophagitis (LA C/D), large hiatal hernia, or persistent troublesome symptoms benefiting most; TIF is suggested only for troublesome regurgitation or heartburn in patients who do not wish to undergo antireflux surgery and who are WITHOUT severe esophagitis (LA C/D) or hiatal hernia >2 cm. For extraesophageal symptoms WITHOUT typical GERD symptoms, perform reflux testing BEFORE starting PPI therapy (strong, moderate); with concomitant typical symptoms, consider twice-daily PPI for 8-12 weeks before further testing (conditional, low). Lifestyle: weight loss in overweight/obese patients (strong, moderate); avoid meals within 2-3 hours of bedtime, avoid tobacco, avoid trigger foods, and elevate the head of the bed for nighttime symptoms (all conditional, low).

For heartburn or regurgitation persisting despite PPI therapy, current practice (ACG 2022 GERD guideline, still the operative ACG guideline, plus the AGA 2022 personalized-GERD CPU) is to first optimize the PPI: confirm adherence, dose 30-60 minutes before meals, escalate to twice-daily dosing or switch agents for an 8-week trial. Empiric escalation to vonoprazan/P-CAB is NOT a routine pre-testing step: the AGA 2024 P-CAB clinical practice update advises against P-CABs as first-line therapy and reserves them for PPI failure with confirmatory GERD evidence (LA grade B or worse erosive esophagitis, biopsy-proven Barrett's, peptic stricture, or acid exposure time >6%). If symptoms persist after optimization, perform EGD (ideally 2-4 weeks off PPI when GERD is unproven) with esophageal biopsies to exclude EoE (>=15 eos/hpf; the ACG 2025 EoE guideline has removed the PPI trial from the diagnostic pathway) and then physiologic testing per Lyon Consensus 2.0: in unproven GERD, ambulatory reflux monitoring OFF therapy, applying Lyon 2.0's modality-specific thresholds -- on catheter-based single-day (24-hour) pH or pH-impedance, AET >6% is conclusive for GERD, 4-6% is inconclusive, and <4% argues against GERD; on prolonged wireless (Bravo, up to 96-hour) monitoring, AET >6% on >=2 days is conclusive for GERD while AET <4% on all days excludes it, and a study meeting neither threshold is inconclusive (the number of days with AET <4% carries prognostic weight for PPI discontinuation) -- and, in either modality, a normal-AET (<4%) study with positive symptom association indicates reflux hypersensitivity or, without it, functional heartburn; in previously proven GERD, pH-impedance ON optimized therapy, where AET >4% plus >80 reflux episodes defines actionable refractory GERD (MNBI <1500 ohms supportive, >2300 ohms against). High-resolution manometry per Chicago Classification 4.0 (still current) excludes achalasia and major motility disorders and is required before anti-reflux surgery. Therapy is phenotype-directed: surgical or endoscopic anti-reflux intervention for confirmed refractory pathologic reflux, and neuromodulators with or without brain-gut behavioral therapy for reflux hypersensitivity and functional heartburn.