Metabolic changes in the lower esophageal sphincter influencing the result of anti-reflux surgical interventions in chronic gastroesophageal reflux disease

Abstract

AIM:With the availability of a minimally invasive approach, anti-reflux surgery has recently experienced a renaissance as a cost-effective alternative to life-long medical treatment in patients with gastroesophageal reflux disease (GERD). We are not aware of the fact whether reflux episodes causing complaints for a long time i.e., at least for one year are associated with metabolic changes in the lower esophageal sphincter, and if so, whether these may influence functional results achieved after anti-reflux surgery. METHODS:Between 1 January 2001 and 31 December 2002 we performed anti-reflux surgery on 79 patients. Muscle samples were taken from the lower esophageal sphincter (LES) in 33 patients during anti-reflux surgery. Inclusion criteria were: LES resting pressure below 10 mmHg and a marked, pH proven acid exposure to the esophagus of at least one year's duration, causing subjective complaints and requiring continuous proton pump inhibitor treatment. Control samples were obtained from muscle tissue in the gastroesophageal junction that had been removed from 17 patients undergoing gastric or esophageal resection. Metabolic and lysosomal enzyme activities and special protein concentrations 16 parameters in total were evaluated in tissue taken from control specimens and tissue taken from patients with GERD. The biochemical parameters of these intra-operative biopsies were used to correlate the results of anti-reflux operations (Visick I and II-III). RESULTS:In the reflux-type muscle, we found a significant increase of the energy-enzyme activities e.g., creatine kinase, lactate dehydrogenase, -hydroxybutyrate dehydrogenase, and aspartate aminotransaminase-. The concentration of the structural protein S-100 and the myofibrillar protein troponin I were also significantly increased. Among lysosomal enzymes, we found that the activities of cathepsin B, tripeptidyl-peptidase I, dipeptidylpeptidase II, -hexosaminidase B, -mannosidase and -galactosidase were significantly decreased as compared to the control LES muscles. By analyzing the activity values of the 9 patients in Visick groups II and III at two months post-surgery, we found a significant increase in the activity of the so-called energy-enzyme values and in the concentration of structural and myofibrillar proteins as compared to the rest of the reflux patients. CONCLUSION:Our results call attention to the metabolic changes that occurred in the LES muscles of reflux patients. The developing hypertrophy-like changes of LES muscles may be a reason for complaints after anti-reflux surgery, which consisted mainly of reports of persisting dysphagia.

Achalasia following reflux disease: coincidence, consequence, or accommodation? An experience-based literature review

“…However, the fact that the standard chronological sequence of symptoms described by several authors in that long-lasting reflux is followed by dysphagia (and never vice versa) seems to suggest that achalasia might be a consequence of GERD. This theory is supported by Altorjay et al, 8 who found enteric ganglionitis and smooth muscle hypertrophy in the muscle samples of the LES of reflux patients. These morphological changes, which are characteristic of achalasia, could be interpreted as consequences of long-term reflux episodes.…”

“…Altorjay et al 8 , 15 reported very interesting observations by analyzing LES muscle specimens of reflux patients and comparing them to a control group. They found hypertrophy-like changes or (more specifically) a significant increase in the concentration of structural protein S-100 and myofibrillar protein troponin I in the LES muscle.…”

“…These morphological changes, which are characteristic of achalasia, could be interpreted as consequences of long-term reflux episodes. 8 At the same time, it is known that the human body has developed several aerodigestive reflexes to protect the airways from aspiration. 9 Similarly, various esophageal pathologies have been presumed to be related to reflux such as hypertensive LES, hypertrophic upper esophageal sphincter (UES), Schatzki’s ring, and achalasia.…”

GERD: A Debated Background of Achalasia

“…A previous study showed that antineuronal antibodies of very similar properties were found in the serum of both achalasia and GERD patients, therefore one can assume that the two diseases may not appear independantly of one another, but they may have common autoimmun mechanisms in their pathogenesis [2]. In another study, comparing LES muscle samples of reflux patients with those of a control group, Altorjay et al revealed that reflux patients had enteric ganglionitis and smooth muscle hypertrophy at the gastroesophageal junction, and they suggested that these morphological changes might result in various functional esophageal diseases [3]. The theory that GERD could be an etiologic factor in the development of achalasia was first proposed by Smart et al in 1986, who described 5 patients presenting with reflux, who subsequently developed achalasia over the years [4].…”

Gastroesophageal Reflux Disease Could Progress to Achalasia

“…Among our own untreated achalasia cases we also had one patient with concomitant Barrett's esophagus and one with hiatal hernia. Altorjay et al 8,9 reported an interesting observation after comparing muscle samples taken from the lower esophageal sphincter of reflux patients and those of a control group. They found that reflux patients had smooth muscle hypertrophy and enteric ganglionitis at the gastroesophageal junction, and they suggested that these morphological changes might result in various functional esophageal diseases.…”