Anatomy - EndoStim® Stimulation Therapy of the Lower Esophageal Sphincter

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder with increasing prevalence worldwide.

Acid suppression with proton pump inhibitors (PPIs) is the standard treatment to control symptoms and complications of GERD. However, it is estimated that up to 40% of patients do not respond or only partially respond to PPI treatment. This unsatisfactory situation is due to the fact that acid suppression does not address the underlying pathophysiology, that is the dysfunctional lower esophageal sphincter.

Fundoplication is a safe and effective procedure for GERD therapy, but it involves side effects such as dysphagia and the inability to belch or vomit. Therefore, only a minority of reflux patients undergo surgery, particularly those with a clearly identifiable anatomical defect such as a large hiatal hernia.

Electrostimulation is increasingly used for various neuromuscular disorders and has recently been introduced as a new minimally invasive treatment option for gastroesophageal reflux disease (GERD) by modulating the dysfunctional lower esophageal sphincter.

The stomach is, formally speaking, an outpouching of the digestive tract located between the esophagus and the intestine, tasked with storing and mixing food. This muscular hollow organ produces acidic gastric juice (mucus and HCl) and enzymes that partially digest some components of food, then gradually pass the chyme into the small intestine.

The stomach is usually located in the left and middle upper abdomen directly beneath the diaphragm. The position, size, and shape of the stomach vary significantly from person to person and depending on age, state of fullness, and body position. When moderately filled, the stomach is on average 25-30 cm long and has a storage capacity of 1.5 liters, and in extreme cases, up to 2.5 liters.

The stomach is anchored and stabilized in the abdominal cavity by ligaments that extend, among other places, to the liver and spleen. It forms the greater curvature (Curvatura major) with its convex side and the lesser curvature (Curvatura minor) with its concave side. Its anterior wall is referred to as Paries anterior, and its posterior wall as Paries posterior.

The stomach is intraperitoneal and thus covered by serosa, with only the dorsal cardia being free of serosa. The embryonic mesogastria rotate from their former sagittal position to a frontal one due to the stomach's rotation: The lesser omentum extends from the lesser curvature to the liver hilum, while the greater omentum spreads from the greater curvature to the transverse colon, spleen, and diaphragm.

The stomach can be divided into different sections:

Cardia / Ostium cardiacum
The upper stomach entrance is an area of 1-2 cm where the esophagus opens into the stomach. Here, the sharp transition from esophageal mucosa to gastric mucosa is usually easily recognizable with an endoscope.

Fundus gastricus
Above the stomach entrance, the fundus arches upward, also known as the "gastric dome" or Fornix gastricus. The fundus is typically filled with air that is involuntarily swallowed during eating. In an upright person, the fundus forms the highest point of the stomach, so in an X-ray, the collected air appears as a "gastric bubble." Opposite the stomach entrance, the fundus is demarcated by a sharp fold (Incisura cardialis).

Corpus gastricum
The main part of the stomach is formed by the gastric body. Here, deep longitudinal mucosal folds (Plicae gastricae) extend from the stomach entrance to the pylorus and are also referred to as the "gastric street."

Pars pylorica
This section begins with the expanded pyloric antrum, followed by the pyloric canal (Canalis pyloricus), and ends with the actual pylorus. Here lies the pyloric sphincter muscle (M. sphincter pylori), formed by a strong circular muscle layer, which closes the lower stomach opening (Ostium pyloricum). The pylorus closes the stomach exit and periodically allows some chyme to pass into the subsequent duodenum.

Gastroesophageal reflux disease (GERD) occurs when reflux of stomach contents into the esophagus causes esophageal or extraesophageal manifestations and/or when symptoms impair quality of life. Although the pathogenesis of GERD is multifactorial, it is primarily due to an insufficiency of the antireflux barrier.

Antireflux Barrier

Since there is a higher pressure in the abdomen than in the thorax, and the gradient increases further with coughing and the Valsalva maneuver, there is a physiological tendency to move stomach contents toward the esophagus, necessitating a well-functioning barrier to prevent reflux. Essential prerequisites for a sufficient antireflux barrier include:

• Function and position of the lower esophageal sphincter ("LES")
• External compression by the diaphragmatic crura
• Acute angle of His between distal esophagus and proximal stomach
  phrenoesophageal ligament

From a pathophysiological perspective, three fundamental forms of an insufficient antireflux barrier can be distinguished, which can occur alone or in combination:

• Transient sphincter relaxation
• Permanently reduced sphincter pressure
• Altered anatomy (e.g., hiatal hernia)

While transient sphincter relaxations dominate in patients with mild reflux disease, severe forms of GERD are often associated with a hiatal hernia and/or permanently reduced sphincter pressure.

Transient Relaxation of the LES

In healthy individuals and reflux patients with normal resting pressure of the LES (> 10 mm Hg), reflux episodes can occur due to transient, swallow-independent relaxations of the LES. Unlike swallow-induced relaxations, transient relaxations are not accompanied by peristaltic esophageal activity and last longer. What distinguishes reflux patients from healthy individuals with transient relaxations is not the frequency of relaxations, but the reflux of gastric acid. In healthy individuals, transient relaxations rarely lead to acid reflux; rather, gas reflux ("belching") is predominant. Triggers for transient relaxations can include vagovagal reflexes induced by distension of the proximal stomach.

Sphincter Apparatus and Hiatal Hernia

The LES is a 3 – 4 cm long, tonically contracted segment of smooth muscle, with a pressure normally ranging from 10 – 30 mm Hg. Its muscular contraction is calcium-dependent, and its neural regulation is cholinergic. If the intra-abdominal pressure exceeds the sphincter pressure—especially with abrupt increases such as coughing—or if the sphincter pressure is very low (0 – 4 mm Hg), reflux of stomach contents into the lower esophagus occurs. In addition to the LES, the approximately 2 cm long diaphragmatic crura play an important role as an "external" sphincter during intra-abdominal pressure increases.

Predisposing to reflux disease is the axial hiatal hernia, where various pathophysiological mechanisms lead to acid reflux into the lower esophagus. The displacement of the LES results in an anatomical separation of the internal and external sphincter apparatus, leading to a loss of the sphincter effect of the diaphragmatic crura. Furthermore, the hernia causes disturbances in LES function with a decrease in basal pressure and an increase in transient relaxation episodes. Acid reflux into the lower esophagus is also facilitated by swallow-induced sphincter relaxations, which are practically never observed in reflux patients without hernia and in healthy individuals.

Acid, Pepsin, and Bile Acids

Acid and pepsin play a central role in the onset of symptoms and lesions in the esophagus. In patients with GERD, the volume of acid secretion is usually normal, but acid and pepsin pass through the insufficient antireflux barrier into the acid-sensitive esophagus. The relevance of acid is underscored by the effectiveness of proton pump inhibitors in GERD therapy and by the correlation of esophageal acid exposure with the extent of erosive damage. The damaging effect of acid and pepsin can be potentiated by bile acids (duodenogastroesophageal reflux, DGÖR). At acidic pH, conjugated bile acids lead to erosions, and at alkaline pH, unconjugated bile acids increase the permeability of the esophageal mucosa.