- Clinical science
Gastroesophageal reflux disease (GERD) is a chronic condition in which retrograde flow of stomach contents into the esophagus causes irritation to the epithelial lining. Reflux episodes are primarily caused by inappropriate, transient relaxation of the lower esophageal sphincter (LES). Risk factors include smoking, alcohol consumption, stress, obesity, and anatomical abnormalities of the esophagogastric junction (e.g., hiatal hernia). The chief complaint is retrosternal burning pain (heartburn), but a variety of other symptoms, such as dysphagia and a feeling of increased pressure, are also common. Suspected GERD should already receive empirical treatment, but further diagnostic steps, such as an upper endoscopy and/or 24-hour pH test, may be indicated to confirm the diagnosis. Management involves lifestyle modifications, medications, and possibly surgery. Proton pump inhibitors (PPIs) are the treatment of choice, although other agents – such as histamine H2-receptor antagonists (H2RAs) – may also be helpful. In addition to relieving symptoms, treating esophagitis is especially important, as chronic mucosal damage can lead to a premalignant condition known as Barrett's esophagus, further progressing to adenocarcinoma of the esophagus.
- Gastroesophageal reflux: regurgitation of stomach contents into the esophagus (can also occur in healthy individuals, e.g., after consuming greasy foods or wine)
Gastroesophageal reflux disease (GERD): A condition in which reflux causes troublesome symptoms (typically including heartburn or regurgitation) and/or esophageal injury/complications. The most common endoscopic finding associated with esophageal mucosal injury is reflux esophagitis.
- NERD (non-erosive reflux disease): characteristic symptoms of gastroesophageal reflux disease in the absence of esophageal injury, such as reflux esophagitis, on endoscopy (50–70% of GERD patients)
- ERD (erosive reflux disease): gastroesophageal reflux with evidence of esophageal injury, such as reflux esophagitis, on endoscopy (30–50% of GERD patients)
- Prevalence: ∼ 15–30% in the US (increases with age)
- Sex: ♀ = ♂
Epidemiological data refers to the US, unless otherwise specified.
- Main mechanism: transient lower esophageal sphincter relaxations (tLESRs)
- Lifestyle habits such as smoking, caffeine and alcohol consumption
- Diaphragm dysfunction
- Angle of His enlargement (> 60°)
- Iatrogenic (e.g., after gastrectomy)
- Inadequate esophageal protective factors (i.e., saliva, peristalsis)
- Gastrointestinal malformations and tumors: gastric outlet obstruction, gastric cardiac carcinoma
- Sliding hiatal hernia: ≥ 90% of patients with severe GERD ,
There are two major grading classifications to assess the severity of reflux esophagitis, both of which are based on macroscopic findings on upper endoscopy. While the Savary-Miller classification is still commonly used, the newer Los Angeles classification has gained widespread acceptance. Although GERD can lead to mucosal changes, most individuals present with unremarkable endoscopic findings (NERD).
Reflux without mucosal damage
Single or multiple non-confluent mucosal erosions
Complications (ulcerations, strictures, intestinal differentiation with columnar epithelium)
- Chief complaint: retrosternal burning pain (heartburn) that worsens while lying down (e.g., at night) and after eating
- Pressure sensation in the chest
- Belching, regurgitation
- Chronic non-productive cough and nocturnal cough
- Nausea and vomiting
- Bending down, supine position
- Habits: smoking and/or alcohol consumption
- Psychological factors: especially stress
- Empirical therapy: If GERD is clinically suspected and there are no indications for endoscopy, empiric therapy – ranging from lifestyle modifications to a short trial with PPIs – should be initiated. A GERD diagnosis is assumed in patients who respond to this therapeutic regimen.
Upper endoscopy (esophagogastroduodenoscopy (EGD))
- Used to classify reflux esophagitis (see “Classification” above) and conduct biopsies
- Indications for endoscopy
Esophageal pH monitoring
- Measured over 24 hours via nasogastric tube with a pH probe
- Sudden drops to a pH ≤ 4 are consistent with episodes of acid reflux into the esophagus
- Event diary: Patients are asked to record the time and duration of relevant events, including food intake, sleep, exercise, and other activities.
- GERD is diagnosed when drops in esophageal pH correlate with symptoms of acid reflux and precipitating activities noted in the patient's event diary.
- A pressure-sensitive nasogastric tube measures the muscle contractions in several sections of the esophagus while the patient swallows.
- Ensure correct placement of pH probes
- Evaluate peristaltic function prior to anti-reflux surgery
- Exclude motor disorders that may mimic the symptoms of GERD
The histopathological findings vary depending on the severity of mucosal damage:
- Superficial coagulative necrosis in the non-keratinized squamous epithelium
- Thickening of the basal cell layer
- Elongation of the papillae in the lamina propria and dilation of the vascular channels at the tip of the papillae (→ hyperemia)
- Inflammatory cells (granulocytes, lymphocytes, macrophages)
- Transformation of squamous into columnar epithelium →
Other forms of esophagitis
- Infectious esophagitis: generally in immunocompromised patients
Drug-induced esophagitis: Some medications may cause esophageal mucosal irritation, leading to erosions and ulcers.
- Endoscopic findings: punched-out ulcers with mild inflammatory changes of the surrounding mucosa
- Eosinophilic esophagitis
Conditions not involving esophagitis
- Cardiac: See (especially angina pectoris).
- Da Costa's syndrome (or neurocirculatory asthenia)
The differential diagnoses listed here are not exhaustive.
- Small portions; avoid eating (< 3 hours) before bedtime
- Avoid foods with high fat content
- Normalize body weight
- Elevate the head of the bed for patients with nighttime symptoms.
- Avoid toxins: nicotine, alcohol, coffee, and certain drugs (e.g., calcium channel blockers, diazepam)
- Treatment of choice; : Standard-dose of PPI for at least 8 weeks (once daily therapy)
- Maintenance therapy: if symptoms recur after discontinuation of PPIs and in the case of complications (see “Complications” below)
- Symptoms resolve in 85% of cases, but recurrence is possible.
- Technique: The gastric fundus is wrapped around the lower esophagus and secured with stitches to form a cuff, leading to a narrowing of the distal esophagus and the gastroesophageal junction (GEJ)and prevents reflux.
Fundoplication types differ in:
- Surgical technique (most commonly laparoscopic vs. open surgery)
- Surgical approach (transthoracic vs. abdominal)
- Part of the stomach wall that is used to form the cuff (posterior vs. anterior)
- Completeness of the cuff (complete vs. partial)
- Looseness and length of the cuff
- Nissen fundoplication (= complete fundoplication)
- Intraoperative damage to the stomach and/or surrounding organs, especially the esophagus, spleen, lungs/pleura (→ pneumothorax)
- Gas bloat syndrome: inability to belch, leading to bloating and an increase in flatulence
Dysphagia (especially to solids)
- Persisting dysphagia
- Dysphagia to solids
- Recurrence of reflux esophagitis
- Telescope phenomenon ("slipped Nissen"): the esophagus slides out of the wrapped stomach portion
- Gastric denervation: Vagal nerve injury leads to bloating and cardiac complaints, resembling
- If hiatal hernia is present
- , possibly inserting mesh for extra support (e.g., if extremely widened or high risk of symptom recurrence) : margins of the widened hiatus are sutured together
- Fundopexy or : the protruding part of the stomach is tethered to the diaphragm → keeps it in place and relieves the tension placed on the cuff
- Reflux esophagitis: most common complication of GERD
- Iron deficiency anemia: mucosal erosions and ulcerations → chronic bleeding → anemia
Esophageal stricture: most common sequela of reflux esophagitis
- Clinical features: cause solid food dysphagia
- First-line treatment: dilation with bougie dilator/balloon dilator + proton pump inhibitors in patients with reflux
- In refractory cases (multiple recurrences): steroid injection prior to dilation, endoscopic electrosurgical incision
- Recurrence occurs in the majority of patients; often multiple treatment attempts necessary
- Schatzki rings at the squamocolumnar junction are the most common type
- Clinical features and management similar to that of an esopahgeal stricture
- Aspiration of gastric contents leads to:
- Laryngitis and hoarseness
Barrett's esophagus (Barrett's metaplasia)
- The stratified squamous epithelium of the lower esophagus is not specialized to tolerate highly acidic stomach acid
- Reflux esophagitis → stomach acid damages squamous epithelium → squamous epithelium becomes replaced by columnar epithelium and goblet cells (intestinal metaplasia, Barrett's metaplasia)
- The physiological transformation zone ("Z-line") between squamous and columnar epithelium is shifted upwards
- Complications: precancerous condition for adenocarcinoma (see )
Management and surveillance
- Medical treatment with PPIs
Endoscopy with four-quadrant biopsies at every 2 cm of the suspicious area (salmon colored mucosa)
- If no dysplasia: repeat endoscopy every 3–5 years
- If indefinite for dysplasia: repeat endoscopy with biopsies after 3–6 months of optimized PPI therapy
- If low-grade dysplasia
- Endoscopic therapy of mucosal irregularities
- Alternatively: surveillance every 12 months with biopsies every 1 cm
- If high-grade dysplasia: endoscopic therapy of mucosal irregularities
We list the most important complications. The selection is not exhaustive.