⁨أسئلة الثانية GIT الدلتا - GERD ⁩

Definitions

• GERD is characterized by the regurgitation of gastric contents into the esophagus or mouth, leading to troublesome symptoms or complications, as per the Montreal Consensus.
• GERD affects all ages and genders, with a global prevalence estimated between 8% and 33%.
• NERD (Non-Erosive Reflux Disease) is a subtype of GERD defined by reflux symptoms with pathologic acid exposure during 24-hour ambulatory pH-impedance monitoring, but without confirmed esophageal mucosal injury on endoscopy.
• Reflux Hypersensitivity involves retrosternal symptoms, like heartburn or chest pain, without pathologic acid exposure on 24-hour ambulatory pH-impedance monitoring, triggered by physiological acid reflux.
• Functional Heartburn is retrosternal burning discomfort or pain that is refractory to acid-suppressive therapy, in the absence of pathologic acid exposure on 24-hour ambulatory pH-impedance monitoring, and is unrelated to physiological acid reflux.

Pathophysiology

• Motor abnormalities include impairment in the tone of the lower esophageal sphincter (LES), transient LES relaxation, impaired esophageal acid clearance, and delayed gastric emptying.
• Anatomical factors contributing to GERD are the presence of a hiatal hernia and increased intra-abdominal pressure, such as from obesity, pregnancy, or postprandial supination.
• Certain drugs and foods can worsen GERD, including caffeine, tobacco, excess alcohol, anticholinergic drugs, benzodiazepines, NSAIDs, aspirin, nitroglycerin, albuterol, CCBs, antidepressants, and glucagon.
• Other risk factors include age ≥ 50 years and connective tissue disorders.

Clinical Presentations

• Typical symptoms of GERD include Heartburn (retrosternal burning or discomfort, sometimes radiating to the neck, occurring after meals or when reclining) and Regurgitation (intermittent, sudden sensation of stomach contents moving toward the esophagus and throat).
• Other symptoms are dysphagia, odynophagia, belching, epigastric pain, and nausea.
• Atypical symptoms (extra-esophageal) include chest pain, chronic cough, asthma, laryngitis, dental erosions, dysphonia, hoarseness, and globus sensation.

GERD Questionnaire (GerdQ) Interpretation

• The GerdQ has six questions.
• Positive predictors are rated on a scale of 0-3 for heartburn, regurgitation, sleep disturbance, and intake of acid suppressant medications.
• Negative predictors are rated on a reversed scale of 3-0 for epigastric pain and nausea.
• The total GerdQ score ranges from 0 to 18 points.
• A cut-off score of ≥ 8 points suggests GERD diagnosis.

Evaluation of GERD

• Patients with typical heartburn and regurgitation symptoms may start PPIs without further investigation.
• Improvement with PPI treatment can confirm a GERD diagnosis.
• Contraindications for PPI trial include alarm symptoms such as dysphagia, odynophagia, anemia, weight loss, or recurrent vomiting/hematemesis.
• Indications for further investigation include GERD symptoms with alarm symptoms, non-response to PPIs, and non-cardiac chest pain suspected to be GERD
• Esophago-gastro-duodenoscopy (EGD) is important for diagnosing and grading erosive esophagitis (Los Angeles grading), Barrett's esophagus (with biopsy), esophageal strictures (with diagnosis and dilatation), esophageal adenocarcinoma (with diagnosis and biopsy), peptic ulcer disease (rule out), and suspected eosinophilic esophagitis (EoE) (with biopsy).
• Biopsy is not routinely recommended for GERD diagnosis per ACG guidelines.

Evaluation for Underlying CVD

• High index of suspicion for coronary artery disease with GERD symptoms is an indication.

Barium Esophagram

• Can detect moderate/severe esophagitis, strictures, hiatal hernia, and tumors.
• Indications include refractory GERD with normal endoscopy, extraesophageal symptoms, and mandatory use before surgery if the patient presents with normal endoscopy.

Ambulatory Esophageal pH Monitoring

• Detects pathological esophageal acid exposure (EAE), the frequency of reflux episodes, and correlation of symptoms with reflux episodes.
• Diagnostic interpretation entails:
• GERD is indicated by pathologic EAE with positive or negative reflux-symptom association.
• EAE refers to the time the esophagus is exposed to pH less than 4.
• EAE greater than 6% of the time within 24 hours confirms GERD.
• Reflux Hypersensitivity presents with physiologic acid exposure with positive reflux-symptom association.
• Functional Heartburn has physiologic acid exposure with no reflux-symptom association.

Bernstein Testing

• A test of mostly historical interest that assesses mucosal sensitivity.
• Procedure involves trans-nasal esophageal intubation and perfusion of distal esophageal mucosa alternating between dilute hydrochloric acid (0.1M) and normal saline, considered positive if acid produces symptoms, while saline does not.
• Can complement pH monitoring for atypical symptoms, especially chest pain, if infrequent/absent during pH monitoring.

Esophageal Manometry

• Is indicated before anti-reflux surgery to exclude achalasia and tailor the tightness of the intended repair.
• Current ACG guidelines recommend against screening for Helicobacter pylori infection in patients with GERD symptoms.

Los Angeles Classification of Erosive GERD

• Grade A: At least one mucosal break (erosion) each ≤ 5 mm
• Grade B: At least one mucosal break > 5 mm but not continuous between the tops of two mucosal folds
• Grade C: At least one mucosal break that is continuous between the tops of 2 mucosal folds, but which is not circumferential (< 75%)
• Grade D: Circumferential mucosal break

Advantages of Multichannel Intraluminal Impedance (MII)

• Assesses the direction of bolus movement (anterograde or retrograde).
• It analyzes the content of the refluxate (liquid, gas, or mixed).
• Assess the height of refluxate, relative to volume of refluxate
• Determines pH characteristics

Grey Zone Diagnosis

• Considers number of reflux episodes, basal impedance, microscopic esophagitis, DeMeester index.
• Less than 40 acid reflux episodes in 24 hours: considered normal.
• More than 80: GERD is diagnosed even if EAE is between 4% and 6% in 24 hours.
• DeMeester score greater than 14.7 establishes the diagnosis of GERD.

Complications of GERD

• Erosive esophagitis.
• Peptic stricture and dysphagia.
• Lower esophageal rings (Schatzki).
• Barrett esophagus.
• Esophageal adenocarcinoma (EAC) more common in men (8:1 ratio).
• Upper gastrointestinal bleeding and anemia.
• Extraesophageal complications: laryngitis, cough, sinusitis, asthma, idiopathic pulmonary fibrosis, dental erosions.

Differential Diagnosis of GERD

• Coronary artery disease.
• Infectious esophagitis, eosinophilic esophagitis, radiation- and chemotherapy-induced esophagitis, esophageal motility disorders, esophageal stricture, esophageal cancer.
• Peptic ulcer disease, gastroparesis, dyspepsia, rumination syndrome, gastric neoplasm.

Barrett's Esophagus (BE)

• Metaplastic transformation from stratified squamous to columnar epithelium in the distal esophagus.
• Occurs in 5-15% with reflux esophagitis.
• Predisposes to adenocarcinoma of the distal esophagus (EAC).
• Risk factors include long-term reflux symptoms, age >50 years, Caucasian race, metabolic syndrome, smoking history, and family history of BE or EAC.
• Endoscopic recognition depends on the presence of columnar epithelium (salmon pink) ≥ 1 cm above the proximal margin of gastric folds (Prague criteria).
• Histological confirmation requires intestinal metaplasia.
• Low- (LGD) and high-grade dysplasia (HGD) may occur as precursors to EAC.
• Based on the segment length:
• Short segment (≤3 cm).
• Long segment (>3 cm).
• BE without dysplasia: follow-up endoscopy after 3 years for long segment BE and after 5 years for short segment BE.
• Management of BE with LGD includes double dose PPI & endoscopic eradication therapy (EET).
• For BE with HGD consider esophagectomy/EET, which involves EMR, ESD, RFA, APC & Cryotherapy.

Treatment of GERD

Lifestyle Modifications:

• Are considered the first option for most patients.
• Weight loss to reduce/eliminate GERD symptoms.
• Avoid smoking, chocolate, carbonated beverages, spicy/fatty foods, alcohol, and large meals.

Sleep Position:

• Reduce acid exposure and improve nocturnal reflux with head of bed elevation, left decubitus positioning.
• No meals for 2-3 hours before bedtime.

Drug Therapy:

• If lifestyle interventions fail, drug options are PPIs, H2RAs, and antacids. PPIs are the therapy of choice, taken 30-60 minutes before a meal (except dex lansoprazole, which can be taken any time of day).
• H2RAs: Useful for controlling nighttime acid breakthrough (defined as acid reflux during the overnight period for at least 60 continuous minutes.)
• Tachyphylaxis (reduced responsiveness) may develop rapidly, limiting use.
• Antacids:
• Effective, especially when combined with alginate preparations, for reducing postprandial esophageal acid.
• Investigational therapies: Reflux inhibitors, prokinetics, acupuncture, hypnotherapy.
• Prokinetics:
• Metoclopramide and domperidone show central nervous system side effects.
• New medical treatments: Potassium competitive acid blockers (PCABs, vonoprazan 20 mg) and bile acid sequestrant that binds to bile in the refluxate

Endoscopic Therapies

• Transoral incisionless fundoplication (TIF): Creates a partial gastric wrap using an Esophyx device mounted on the endoscope.
• Radiofrequency energy to the LES (Stretta): Delivers thermal energy, increasing sphincter thickness to reduce reflux.
• Endoscopic anterior fundoplication: Uses Medigus ultrasonic surgical endo-stapler.

Surgical Therapies

• Anti-reflux surgery should be recommended with caution due to side effects.
• Esophageal manometry screens for esophageal aperistalsis before surgery.
• Anti-reflux surgery is not recommended in PPI non-responders.
• ACG guidelines suggest surgical therapy is generally not recommended in patients with GERD who do not respond to PPI therapy. Patients with normal endoscopic findings with persistent GERD symptoms while receiving PPI therapy are much less likely to respond to surgery.
• Nissen fundoplication: Reduces hiatal hernia and wraps gastric fundus to restore the LES barrier, indications: presence of large hiatal hernia, reflux esophagitis, and GERD symptoms that are refractory to medical therapy, or adverse effects of medical therapy.

Other surgical approaches

• Linx procedure: Minimally invasive, laparoscopic insertion of magnetic beads around the LES, allowing passage of food but preventing reflux.
• Roux-en-Y gastric bypass: Surgical for morbidly obese patients.

Refractory GERD

• Is GERD that does not respond to a standard dose of PPI for ≥ 8 weeks, and occurs in up to 40% of patients.
• Non-GERD causes include functional heartburn, functional dyspepsia, esophageal motility disorder (achalasia), and eosinophilic esophagitis.
• Insufficient acid suppression can result from lack of compliance, improper dosing time, reduced bioavailability of PPIs, and a hypersecretory state.
• Weakly acidic or non-acidic reflux due to concomitant functional disorder, delayed gastric emptying, or reflux hypersensitivity are also causes.

Management includes

• Endoscopy with biopsies to evaluate for EoE.
• Esophageal impedance and pH testing while off PPIs to determine persistent acidic/nonacidic reflux
• If normal esophageal acid exposure (EAE), continued symptoms from reflux hypersensitivity/functional heartburn require reassurance and neuromodulators.
• Neuromodulators: Selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, or tricyclic antidepressant can be used.
• In non-acid reflux, baclofen can reduce LES transient relaxations.

Baclofen

• Reduces reflux episodes by 40% by increasing LES basal pressure and accelerating gastric emptying.
• Dose is up to 20 mg tid.
• Side effects are central nervous system symptoms, somnolence, confusion, and trembling, which limits routine usage.
• Indications include weakly acidic reflux and regurgitation or a sour/bitter taste in the mouth.