Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Esophagogastric  Junction

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Volume: The Esophagogastric Junction
Chapter: GER and barrier dysfunction

What is the proportion of normal lower esophageal sphincter in gastroesophageal reflux patients?

M. Costantini, G. Zaninotto, M. Anselmino,
C. Boccù, E. Ancona (Padova)

After the identification of the lower esophageal sphincter (LES) as a high-pressure zone in the region of the gastroesophageal junction by Fyke et al. some 40 years ago [1], much interest has been focused on the role of the LES as the major antireflux barrier. It soon became evident that patients with symptomatic esophagitis do have a LES pressure lower than controls, but with a considerable overlap between LES pressure in symptomatic patients and healthy subjects. This led to extensive speculation and some confusion as to the relevance of LES in the complex antireflux mechanism. The usefulness of the manometric evaluation of the LES has also been questioned by some authors [2, 3].

More recently, a better understanding of the characteristics of the LES in health and disease has emerged from the introduction of 24-hour pH monitoring, which enabled a correct pathophysiological definition and diagnosis of gastroesophageal reflux disease (GERD), defined as an increased exposure of the distal esophagus to refluxed gastric juice, and from progress in manometric technology, particularly with the introduction of computerized systems.

In the last decade, extensive studies (especially by DeMeester's group) demonstrated that the simple measurement of resting LES pressure was not enough to characterize LES competence. The first additional measurement to be investigated, both in vitro and in vivo, was the length of LES exposed to the positive pressure of the abdomen (LES abdominal length): the proportion of symptomatic patients with excessive acid exposure was significantly higher when the LES abdominal length was less than 1 cm [4]. Further investigations demonstrated the relevance of the overall length of the LES too, the sphincter being incompetent when it was less than 2 cm long [5]. The integration of these measurements in a study of 50 healthy volunteers and 622 patients with GER symptoms enabled a definition of the normally competent and the mechanically defective cardia [6]. A normal range could be established for these three parameters (LES pressure, overall and abdominal length), set between the 5th and 95th percentiles of the values measured in healthy subjects (non parametric measurements were used for the skewed distribution of the data) (Table I) [7]. The LES was therefore defined as "defective" if the value of any of these three components fell below the normal range of healthy subjects, i.e. below the 5th percentile values. It was found that if one component was defective, the prevalence of increased acid exposure was 70-75%, increasing to 88% and to 92% if two or all three components were abnormal.

Overall, a defective sphincter is found in 55-60% of patients with GERD [6, 8]. In our own experience, using the same criteria in a series of unselected patients, the prevalence of a defective LES was 43%. This was probably related to the lower number of patients with severe esophagitis. In fact, the prevalence of patients with a defective sphincter was found to correlate with the severity of mucosal damage, i.e. it was 28% in patients with endoscopically undetectable esophagitis, 65% in patients with erosive esophagitis, 89% in patients with strictures and 93% in patients with Barrett's esophagus [8].
Table I. Lower esophageal sphincter manometric p

The introduction of computer systems for the digital acquisition and processing of manometric pressure signals enabled a more precise and thorough evaluation of the mechanical characteristics of the LES, introducing new measurements which integrate the pressure values around the LES circumference and along its length. These are the area under the curve (LES-AUC) and the so-called three-dimensional LES vector volume (LES-VV) [9, 10]. The latter best represents the total resistance offered by the sphincter to the reflux of gastric contents. In our experience, using these new measurements increases the sensitivity of manometry in detecting patients with a defective sphincter from 43% to about 60%, without losing in specificity [9]. Another study confirmed that computer analysis and calculation of the LES-VV was more accurate than traditional manometry in detecting a defective LES, increasing its sensitivity from 64% to 75%: this has been shown to be particularly true in the subgroup of patients with no mucosal damage [10].

However, even using these sophisticated techniques, it appears evident that in about one-third of patients with 24-hour pH-proven GERD, the LES is normal, i.e. with a resting pressure, overall length, abdominal length, area under the curve and vector volume within the normal range.

In an attempt to better elucidate the cause of GER in such patients, the attention of researchers has been focused on the dynamic aspects of LES function. This was made possible by the introduction of the so-called Dent sleeve [11], which consists in a 5 cm-long sleeve-perfused sensor which records the maximum pressure coming to bear on its membrane anywhere on its surface, thus compensating for axial movements of the sphincter during swallowing or deep breathing, and allowing for prolonged monitoring of LES pressure. With this system, it was demonstrated that the LES undergoes short periods of relaxation, during which acid reflux may occur [12]. These events are called transient LES relaxations (TLESRs), and are the mechanism whereby reflux occurs in normal subjects who, by definition, have a mechanically normal LES. This phenomenon is also present in patients with esophagitis. Early studies showed that TLESRs were responsible for up to two-thirds of all reflux episodes in patients with esophagitis, the others being due to transient episodes of increased intra-abdominal pressure and periods of prolonged LES hypotonia [13]. This finding seemed to cast doubts on the usefulness of measuring the mechanical characteristics of the LES at rest. However, subsequent studies showed that pharyngeal events (non-transmitted swallows) frequently precede TLESRs [14], so some TLESRs may actually represent swallows (and consequent LES relaxations) without a corresponding peristaltic wave. It was also demonstrated that the frequency of TLESRs is related to the presence of the manometric catheter in the pharynx, suggesting that at least some TLESRs are artefacts [15]. Moreover, the frequency of TLESRs is increased by stomach distention due to gas or after a meal in the upright position [16], and may therefore be part of the belch reflux that occurs in response to gastric distention. Therefore, while there is general consensus that TLESRs are the mechanism of reflux in normal subjects, their significance in the etiology of GERD requires further study. Many conditions associated with gastric pathology (such as hypersecretion, delayed gastric emptying and gastric dilation) may cause reflux through this mechanism.


In conclusion, we can simplify the complex anti-reflux mechanism by representing it as a mechanical model in which the esophageal body acts as a pump, the LES as a valve and the stomach as a reservoir. GERD results from a defect in any of these mechanisms. Figure 1 represents the distribution of the causes of GERD in a consecutive series of 355 patients [17]. The most common abnormality is in the LES, which is mechanically defective in about two-thirds of patients with GERD. It is important to identify such situations, because a defective LES is related to poor response to medical therapy and leads to drug dependence [18]. It is also irreversible, persisting even after endoscopic healing of esophagitis [19]. Finally, such patients respond better to surgical treatment, since surgery restores the mechanical characteristics of the LES to normal.

On the other hand, in some patients with a normal valve the other two components (the pump and reservoir) may be affected. Isolated defects of the pump are rare, since they are usually associated with LES deficiency, but they can cause important excessive esophageal acid exposure due to abnormal wave progression, defective contractility or inadequate salivation. Alterations of the gastric reservoir are more common: they consist in hypersecretion [20], delayed gastric emptying [21] and gastric dilation, especially in response to large or fatty meals. These gastric abnormalities can probably cause reflux episodes by inducing TLESRs. The identification of these patients, who represent about one-third of all patients with GERD, is also important, because they respond well to medical treatment, which can eventually be discontinued in about half of them without recurrence of symptoms [19].

Figure 1. Distribution of the causes of gastroesophageal reflux in a consecutive series of 355 patients with increased esophageal exposure to gastric juice [17].


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Publication date: May 1998 OESO©2015