epidermal-growth-factor and Gastroesophageal-Reflux

Barrett's esophagus is an acquired metaplastic change that occurs in the distal esophagus secondary to chronic gastroesophageal reflux. This premalignant condition forms the most important risk factor for developing esophageal adenocarcinoma, which is an extremely aggressive tumor with a 5-year survival rate of less than 25%. Carcinomas that arise in the setting of Barrett's esophagus are thought to develop as part of the metaplasia-dysplasia-carcinoma sequence.. To review the current knowledge on the genomic alterations involved in the development of Barrett's esophagus and its progression to dysplasia and/or cancer.. Several changes in gene structure, gene expression, and protein structure are associated with the progression of Barrett's esophagus to adenocarcinoma. Accumulation of these changes seems to be essential, rather than the exact sequence of these changes. Multiple molecular pathways are involved and interact with each other. Alterations in tumor suppressor genes, amongst which p53 and p16, are early events in the metaplasia-dysplasia-adenocarcinoma sequence, followed by loss of cell cycle checkpoints. Ongoing genomic instability leads to cumulative genetic errors and thereby the generation of multiple clones of transformed cells.. Within the multistep process of esophageal adenocarcinogenesis, to date no single molecular marker came forward able to predict who will and who will not develop cancer in the setting of Barrett's esophagus. Instead, panels of markers need to be developed in the future allowing to indicate disease progression. Identification of crucial molecular pathways involved in esophageal adenocarcinogenesis would ultimately improve therapy and facilitate development of new treatment strategies.

Topics: Adenocarcinoma; Apoptosis; Barrett Esophagus; Chromosome Aberrations; Cyclin D1; DNA, Neoplasm; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Gastroesophageal Reflux; Gene Expression Regulation, Neoplastic; Humans; Metaplasia; Microsatellite Repeats; Precancerous Conditions; Receptor, ErbB-2; Tumor Suppressor Protein p53

Oesophageal mucosa has well established protective mechanisms, which operate within pre-epithelial, epithelial and post-epithelial compartments. Since refluxed acid and pepsin always act from the luminal side of the mucosa, protective factors like EGF, operating as a part of pre-epithelial defence, are thought to be pivotal in the maintenance of the integrity of the oesophageal mucosa. The significant contribution of salivary EGF to the quality of the oesophageal mucosal barrier has been demonstrated in an experimental setting and in a clinical scenario. Patients with low salivary EGF levels are predisposed to severe oesophageal damage if they develop gastro-oesophageal reflux and are a high-risk group for development of Barrett's oesophagus. Not only the salivary glands but also the human oesophagus has a profound ability to elaborate and release EGF. Some changes in luminal release of EGF during oesophageal mucosal exposure to intraluminal damaging factors imply its role in the oesophageal protective mechanisms. To exert biological effects within the oesophageal mucosal compartment, EGF requires binding to the ligand-binding domain of its receptor. This process results in receptor dimerisation, autophosphorylation and activation of intracellular signal transduction pathways. EGF receptors are localised on the basolateral and luminal aspect of the mucosal cells playing an important role in fast regeneration of oesophageal epithelium through the high mitotic activity of its proliferative zone. An increase in the rate of salivary EGF secretion during masticatory stimulation suggests its potential therapeutic benefit in the treatment of patients with damaged oesophageal mucosa.

Topics: Barrett Esophagus; Epidermal Growth Factor; Esophagus; Gastroesophageal Reflux; Humans; Mucous Membrane; Saliva

Aggressive factors operating within the esophageal lumen during gastroesophageal reflux are balanced by adequately mobilized protective mechanisms. Esophageal mucosal protection operates at three different although complementary dimensions: (1) preepithelial, (2) epithelial and (3) postepithelial. Since aggressive factors predominantly operate within the esophageal lumen, preepithelial defense is pivotal in mucosal protection. The preepithelial barrier is significantly enhanced by the quantity and the quality of salivary organic components such as salivary mucin, nonmucin protein, salivary epidermal growth factor (EGF) and salivary prostaglandin E2. The rate of secretion of salivary mucin, nonmucin protein and EGF under the impact of intraesophageal mechanical (bolus) and chemical (HCl/pepsin) stimulation, mimicking the natural gastroesophageal reflux scenario, is significantly impaired in patients with RE, whereas the rate of salivary PGE2 output remains essentially unchanged. Salivary secretory response to esophageal mechanical and chemical stimuli in terms of organic components, mediated by the esophagosalivary reflex pathway, exhibits a significant impairment in patients with reflux esophagitis.

Topics: Dinoprostone; Epidermal Growth Factor; Gastroesophageal Reflux; Humans; Mucins; Mucous Membrane; Saliva

Reflux of gastric acid and pepsins into the lower oesophagus causes symptoms such as heartburn and nausea, and tissue injury leading to erosive oesophagitis and stricture formation. This article reviews the mechanisms involved in protecting the oesophagus against acid-mediated injury, including the role of the lower oesophageal sphincter, secondary oesophageal peristalsis and swallowed saliva. The oesophageal mucosa has inherent abilities to resist acid damage, and recent data from three laboratories suggest a secretory function with local production of bicarbonate and mucus responsive to local acidification. The evidence for these putative oesophageal defence mechanisms is discussed.

Topics: Animals; Epidermal Growth Factor; Esophagitis, Peptic; Esophagus; Gastroesophageal Reflux; Humans; Mucous Membrane; Saliva

Considerable evidence now demonstrates that saliva and its components have multiple functions in the GI tract. Saliva aids in bolus formation; it lubricates, protects and cleanses the pharyngeal and esophageal mucosa. Salivary bicarbonate buffers esophageal acid in common reflux. Normal salivary flow decreases the duration of acid contact with esophageal mucosa, an important factor in the development of GERD. If salivary flow is depressed or if the esophagosalivary reflex is lost, a patient may be predisposed to develop GERD. Salivary EGF stimulates GI mucosal proliferation via a direct lumenal effect in the esophagus and stomach. The salivary enzymes LL and salivary amylase initiate fat and starch digestion. They are particularly significant in patients with pancreatic insufficiency such as neonates and patients with cystic fibrosis.

Topics: Amylases; Digestion; Digestive System Physiological Phenomena; Epidermal Growth Factor; Gastroesophageal Reflux; Humans; Lipase; Reflex; Saliva; Salivation

The development of esophageal damage depends on a number of factors. The components in the refluxate, including H+ ion, pepsin, bile salts, and pancreatic enzymes, are able to permeate the mucosa and cause injury. These agents may act individually or in combination. Balancing the effects of these damaging agents is the "esophageal mucosal barrier." This barrier is an integrated complex of anatomic and physiologic components that acts to maintain the integrity of the mucosa. Although the relative efficacy of the various components in developing an effective barrier is not understood completely, their physiologic and clinical importance in the face of "noxious" luminal contents remains critical. Understanding the interplay between the injurious agents in the refluxate and the esophageal mucosal barrier may allow for the development of new therapeutic measures in the treatment and prevention of gastroesophageal reflux disease.

Topics: Bile Acids and Salts; Cell Division; Epidermal Growth Factor; Esophagitis, Peptic; Esophagus; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Mucous Membrane; Pepsin A; Regional Blood Flow

Sex differences in salivary secretion have been reported among healthy subjects. In the present study, salivary secretion and salivary epidermal growth factor (EGF) concentrations were investigated in mild reflux esophagitis patients, non-erosive reflux disease (NERD) patients, and healthy controls by matching the sex ratio.. Thirty-three (male:female = 11:22) patients with NERD, 33 (11:22) with mild reflux esophagitis, and 33 (11:22) healthy controls were recruited for this case-control study. Salivary secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount of saliva secretion, salivary pH, and salivary pH after acid loading as an index of the acid-buffering capacity were measured. Salivary EGF concentrations were measured by ELISA.. No significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between the mild reflux esophagitis and NERD groups. However, the amount of saliva secretion and the acid-buffering capacity in the mild reflux esophagitis group and the amount of saliva secretion, salivary pH, and the acid-buffering capacity in the NERD group were significantly lower than those in the healthy control group. No significant differences were noted in salivary EGF concentrations between the mild reflux esophagitis and NERD groups.. After matching the sex ratio, the saliva secretion was significantly lower in patients with mild reflux esophagitis and NERD than in healthy controls. However, no significant differences were observed in the amount of saliva secretion or salivary EGF concentrations between both groups.

Topics: Case-Control Studies; Endoscopy, Gastrointestinal; Epidermal Growth Factor; Esophagitis, Peptic; Female; Gastroesophageal Reflux; Humans; Male

Gastroesophageal reflux disease (GERD) may present as nonerosive reflux disease (NERD), erosive esophagitis (EE), or be complicated by Barrett's esophagus (BE). The explanation as to what determines the phenotype of GERD is awaited. Therefore, we assessed the correlation between the growth factors expression and endoscopic as histologic findings in GERD patients.. The squamous esophageal epithelium of 50 patients (20-NERD, 7-EE, 15-BE, 8 controls) was examined by: (1) magnification endoscopy with evaluation of minimal GERD changes such as: microerosions, white spots, palisade blood vessels visibility, and intrapapillary capillary loops (IPCLs) appearance, (2) histology, (3) immunohistochemistry with evaluation of the expression of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and their receptors (VEGFR and EGFR).. The expression of VEGF, but not VEGFR, EGF, and EGFR, was significantly increased in EE patients compared to NERD patients and controls. VEGF levels correlated significantly with the presence of white spots, but not with other minimal endoscopic and histologic features. The EGFR expression correlated positively with basal cell hyperplasia and enlarged IPCLs.. Our findings suggest a correlation between growth factors expression and findings in conventional endoscopy, formation of endoscopic minimal changes, and histologic lesions.

Topics: Barrett Esophagus; Carcinoma, Squamous Cell; Endoscopy, Gastrointestinal; Epidermal Growth Factor; ErbB Receptors; Esophageal Mucosa; Gastroesophageal Reflux; Humans; Phenotype; Vascular Endothelial Growth Factor A

Sjögren syndrome was chosen as a clinical model to study acinar salivary deficiencies in the development of laryngopharyngeal reflux (LPR). The objective of this prospective cohort study was to compare salivary epidermal growth factor (EGF) concentrations of patients with Sjögren syndrome with and without LPR and gastroesophageal reflux disease (GERD) with normal controls. LPR was diagnosed with positive scores on the Reflux Symptom Index and Reflux and Reflux Finding Score, corroborated by esophagogastroduodenoscopy and/or 24-hour pH-metry. Salivary EGF concentrations of both unstimulated and mechanically stimulated saliva were established using enzyme-linked immunosorbent assay, and the significance level was set at 95%. Twenty-one patients and 19 controls were studied. All patients had LPR and 60% also had GERD. The mean salivary EGF concentration of unstimulated and stimulated saliva in the control group was 1,751.37 pg/ml and 544.76 pg/ml, respectively. Unstimulated and stimulated salivary EGF concentrations in the study group were 2,534.65 pg/ml and 920.69 pg/ml, respectively. These differences were not statistically significant. Body mass index, presence of erosive esophagitis, or severity of hyposalivation did not significantly influence salivary EGF concentrations. LPR and GERD are highly prevalent in patients with Sjögren syndrome. Unlike previous studies in which significant EGF deficiencies were found in patients with reflux laryngitis and GERD, patients with Sjögren syndrome seem to have reflux caused by a decrease in clearance capacity and not in specific salivary components.

Topics: Acinar Cells; Adult; Brazil; Cohort Studies; Endoscopy, Digestive System; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Esophageal pH Monitoring; Female; Gastroesophageal Reflux; Humans; Laryngopharyngeal Reflux; Male; Middle Aged; Prospective Studies; Saliva; Salivary Glands; Sjogren's Syndrome; Statistics as Topic; Symptom Assessment

It has been previously demonstrated that patients with reflux esophagitis exhibit a significant impairment in the secretion of salivary protective components versus controls. However, the secretion of salivary protective factors in patients with nonerosive reflux disease (NERD) is not explored. The authors therefore studied the secretion of salivary volume, pH, bicarbonate, nonbicarbonate glycoconjugate, protein, epidermal growth factor (EGF), transforming growth factor alpha (TGF-α) and prostaglandin E2 in patients with NERD and compared with the corresponding values in controls (CTRL).. Salivary secretion was collected during basal condition, mastication and intraesophageal mechanical (tubing, balloon) and chemical (initial saline, acid, acid/pepsin, final saline) stimulations, respectively, mimicking the natural gastroesophageal reflux.. Salivary volume, protein and TGF-α outputs in patients with NERD were significantly higher than CTRL during intraesophageal mechanical (P < 0.05) and chemical stimulations (P < 0.05). Salivary bicarbonate was significantly higher in NERD than CTRL group during intraesophageal stimulation with both acid/pepsin (P < 0.05) and saline (P < 0.01). Salivary glycoconjugate secretion was significantly higher in the NERD group than the CTRL group during chewing (P < 0.05), mechanical (P < 0.05) and chemical stimulation (P < 0.01). Salivary EGF secretion was higher in patients with NERD during mechanical stimulation (P < 0.05).. Patients with NERD demonstrated a significantly stronger salivary secretory response in terms of volume, bicarbonate, glycoconjugate, protein, EGF and TGF-α than asymptomatic controls. This enhanced salivary esophagoprotection is potentially mediating resistance to the development of endoscopic mucosal changes by gastroesophageal reflux.

Topics: Adult; Dinoprostone; Epidermal Growth Factor; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Physical Stimulation; Saliva; Salivary Elimination; Salivary Glands; Sodium Chloride; Stimulation, Chemical; Transforming Growth Factor alpha

Gastroesophageal reflux disease (GERD) is a pathology with a wide range of clinical and endoscopic manifestations. Epidermal growth factor receptor (EGFR), found in the epithelium of the digestive tract, plays an important role in epithelial repair and shows increased expression in different neoplasms, including esophageal tumors.. The purpose of this study was to evaluate EGFR expression using immunohistochemistry in esophageal biopsies obtained from patients with GERD, Barrett's esophagus, and adenocarcinoma of the esophagus.. EGFR expression was immunohistochemically determined in biopsies from 194 patients with symptoms suggestive of GERD or adenocarcinoma of the esophagus, seen at two Brazilian university hospitals between January 2003 and December 2008. Based on histopathological analysis, patients were divided into three groups: GERD, Barrett's esophagus and adenocarcinoma of the esophagus. EGFR expression was considered positive when staining was detected in the membrane.. Mean age was 55.25 years (range 30-90). Patients with GERD (n = 127) accounted for 65.5% of the sample, compared with 12.4% (n = 24) of patients with Barrett's esophagus and 22.2% (n = 43) of patients with esophageal adenocarcinoma. Immunohistochemical analysis was positive for EGFR in 19.1% of the patients (37/194), divided as follows: 8.7% (11/127) in the GERD group, 25% (6/24) in the Barrett's esophagus group, and 46.5% (20/43) in the esophageal adenocarcinoma group. Statistical analysis revealed significant differences between the three groups (p = 0.0001).. GERD patients showed lower levels of EGFR expression than patients with Barrett's esophagus or patients with adenocarcinoma of the esophagus, suggesting a direct relationship between EGFR expression and disease progression.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Epidermal Growth Factor; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Gene Expression Regulation; Humans; Male; Middle Aged

Single-nucleotide polymorphisms of key cancer genes, such as EGF A61G, are associated with an elevated risk of esophageal adenocarcinoma (EAC). As gastroesophageal reflux disease (GERD) is an established risk factor for EAC, we evaluated whether the association between epidermal growth factor (EGF) polymorphism and EAC development is altered by the presence of GERD.. EGF genotyping of DNA samples was performed and GERD history was collected for 309 EAC patients and 275 matched healthy controls. Associations between genotypes and EAC risk were evaluated using adjusted logistic regression. Genotype-GERD relationships were explored using analyses stratified by GERD history and joint effects models that considered severity and duration of GERD symptoms.. EGF variants (A/G or G/G) were more common (P = 0.02) and GERD was more prevalent (P < 0.001) in cases than in controls. When compared with the EGF wild-type A/A genotype, the G/G variant was associated with a substantial increase in EAC risk among individuals with GERD [Odds ratio 9.7; 95% confidence interval (CI), 3.8-25.0; P < 0.001] and a slight decrease in risk for GERD-free individuals (odds ratio 0.4; 95% CI = 0.22-0.90; P = 0.02). In the joint effects models, the odds of EAC was also highest for G/G patients (when compared with A/A) who either experienced frequent GERD of more than once per week (odds ratio 21.8; 95% CI = 5.1-94.0; P < 0.001) or suffered GERD for longer than 15 years (odds ratio 22.4; 95% CI = 6.5-77.6; P < 0.001). There was a highly significant interaction between the G/G genotype and the presence of GERD (P < 0.001).. EGF A61G polymorphism may alter EAC susceptibility through an interaction with GERD.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Case-Control Studies; Epidermal Growth Factor; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Prognosis; Risk Factors; Survival Rate; Young Adult

The epidermal growth factor (EGF) pathway is important in esophageal adenocarcinoma (EAC) tumorigenesis. We hypothesized that the EGF A61G homozygous variant genotype (GG) is (a) both a risk and poor prognostic factor for EAC and (b) associated with higher EGF serum levels in individuals with gastroesophageal reflux disease (GERD).. Using unconditional logistic regression, we compared EGF A61G in 312 EAC cases and 447 GERD-free controls, adjusting for age, gender, smoking history, and healthy adult body mass index. Using the method of Kaplan and Meier, log-rank tests, and Cox proportional hazard models, we correlated EGF A61G with overall and failure-free survival in the EAC cases. Serum EGF levels and EGF genotype (G/G versus others) were correlated in 144 GERD patients using Wilcoxon rank sum tests.. The EGF A61G G/G genotype conferred increased EAC risk, with an adjusted odds ratio of 1.81 (95% confidence interval, 1.2-2.7), and was even higher in the subgroup of EAC patients with concurrent Barrett's esophagus (adjusted odds ratio, 2.18; 95% confidence interval, 1.3-3.7). However, EGF A61G was not associated with a more aggressive phenotype or prognosis in EAC patients. Higher serum EGF levels were found in GERD patients carrying G/G compared with A/A or A/G (P = 0.03, Wilcoxon rank sum test).. The EGF A61G G/G genotype is associated with a near 2-fold greater risk of EAC. The G/G allele was also associated with higher EGF levels in tumor-free patients with GERD. EGF genotyping can potentially identify high-risk patients with GERD and Barrett's metaplasia who might benefit from increased surveillance.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Genetic Predisposition to Disease; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Polymorphism, Single Nucleotide; Precancerous Conditions; Risk Factors; Treatment Outcome

Topics: Adult; Endosonography; Epidermal Growth Factor; Esophagoscopy; Follow-Up Studies; Gastroesophageal Reflux; Humans; Laryngitis; Laryngoscopy; Magnetic Resonance Imaging; Male; Proton Pump Inhibitors; Proton Pumps; Risk Assessment; Severity of Illness Index; Treatment Outcome; Zollinger-Ellison Syndrome

The mechanisms involved in the mucosal alterations of laryngopharyngeal reflux (LPR) have not been well established. Reports indicate a decrease in the salivary epidermal growth factor (EGF) of patients with reflux esophagitis, but there are no reports of its behavior in LPR. Our objective was to determine the salivary concentration of EGF in adults with LPR.. Salivary EGF concentration of 26 patients with LPR and 20 healthy controls was determined using a commercially available ELISA kit. Patients with LPR were graded according to endoscopic and laryngoscopic criteria.. Salivary EGF concentration was significantly lower in the LPR group when compared with controls (P = 0.002). No correlation between the severity of laryngeal findings or esophagitis and salivary EGF concentration could be determined.. The decreased salivary concentration of EGF in adults with LPR suggests that a deficiency in this polypeptide could be associated to the disease.

Topics: Adult; Aged; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Gastroesophageal Reflux; Humans; Laryngitis; Male; Middle Aged; Saliva

Salivary bicarbonate and epidermal growth factor (EGF) have an important protective role in the oesophagus. The effect of smoking cessation on these aspects of salivary function is unknown.. Salivary bicarbonate secretion and EGF output were measured before and after attempted smoking cessation in 28 healthy volunteers. Urinary cotinine excretion was used to assess compliance.. Negative correlations were found between salivary flow rate and age (rho = -0.34) and between cigarette consumption and salivary flow (rho = -0.27) and salivary bicarbonate concentrations (rho = -0.32). Smoking cessation was associated with a significant increase in salivary bicarbonate secretion (day 0, 1.7 (0.14-6.2); day 7, 3.6 (0.52-6.4); day 21, 3.3 (0.44-6.6) micromol min(-1); P < 0.01) but left salivary EGF output unchanged.. Smoking cessation is associated with significant improvements in salivary bicarbonate secretion. This would benefit patients with reflux disease who stop smoking.

Topics: Adult; Bicarbonates; Epidermal Growth Factor; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Saliva; Secretory Rate; Smoking Cessation

Secretion of salivary protective factors in patient s with gastroesophageal reflux disease is impaired. However, the impact of physiological stimulus mastication on salivary protective factors output remains largely unknown. The aim of this study was to measure salivary volume, pH, HCO3-, peptide growth factors, prostaglandin, mucin, protein, and viscosity during mastication.. In 31 asymptomatic volunteers and 36 patients with endoscopic reflux esophagitis, in basal and parafilm chewing-stimulated saliva, its volume, pH, bicarbonate, epidermal growth factor, transforming growth factor alpha, prostaglandin E2, mucin, protein, and viscosity were investigated.. Masticatory stimulation in controls resulted in a significantly increased salivary volume by 205%, pH by 7.6%, bicarbonate by 335%, mucin by 137%, protein by 98%, epidermal growth factor by 123%, and prostaglandin E2 by 132%, accompanied by an increase in transforming growth factor alpha by 80% with 19% decline in viscosity vs. basal values. Mastication in reflux esophagitis significantly increased salivary volume by 215%, pH by 6.8%, bicarbonate by 257%, mucin by 135%, protein by 94%, epidermal growth factor by 207%, and prostaglandin E2 by 240%, whereas transforming growth factor alpha increased by 225% and viscosity by 64% when compared with corresponding basal values.. A profound and significant increase in the secretion rate of inorganic and organic protective components in saliva during masticatory stimulation suggests its potential value as a therapeutic approach to the treatment of patients with gastroesophageal reflux disease.

Topics: Adult; Aged; Bicarbonates; Dinoprostone; Epidermal Growth Factor; Esophagitis; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Mastication; Middle Aged; Mucins; Saliva; Salivary Proteins and Peptides; Viscosity

Our objective was to investigate the putative role of epidermal growth factor (EGF) in esophagitis pathogenesis in both nondrinkers and chronic alcoholics. We studied the EGF serum level, the EGF salivary concentration, and the esophageal EGF receptor expression in different groups of patients with esophagitis: nondrinkers with typical symptoms of gastroesophageal reflux (N = 12) and chronic alcoholics (N = 12), and in controls: chronic alcoholics without esophagitis (N = 16) and healthy nondrinkers (N = 12). All patients had an endoscopy with esophageal biopsies, 24-hr esophageal pH-metry, and esophageal manometry. EGF serum levels and EGF salivary concentrations were determined by radioimmunoassay. EGF receptor expression was determined by immunohistochemistry. Both the EGF serum level and the EGF salivary concentration remained constant, 328 +/- 21 pg/ml and 305 +/- 48 pg/ml, respectively, regardless of alcohol intake and the presence or absence of esophagitis. In addition, the presence of esophagitis did not affect the EGF receptor expression. These results suggest that seric and salivary EGF is not involved in the pathogenesis of reflux esophagitis in nondrinkers and in chronic alcoholics.

Topics: Adult; Alcoholism; Epidermal Growth Factor; ErbB Receptors; Esophagitis; Esophagitis, Peptic; Esophagus; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Immunohistochemistry; Male; Manometry; Middle Aged; Monitoring, Physiologic; Prospective Studies; Radioimmunoassay; Saliva

Various defence mechanisms are found in the oesophagus which can be elicited by reflux damage. Premucosal defence includes bicarbonate ions and epidermal growth factor (EGF) secreted by salivary and oesophageal glands. The mucosa can respond by increasing epithelial cell turnover and upregulating EGF receptor and endocytosis. The intercellular barrier can be increased by the contents of membrane-coating granules. Local pH can be regulated by carbonic anhydrase. The whole viscus can exhibit peristalsis to effect a mechanical clearance of the refluxed gastric and duodenal material.

Topics: Animals; Epidermal Growth Factor; ErbB Receptors; Esophagus; Gastroesophageal Reflux; Humans; Mucous Membrane