Esophageal histology in gastroesophageal reflux

Esophageal suction biopsies were taken in 24 subjects with proven gastroesophageal reflux, 12 subjects with suspected reflux, and 20 healthy controls. Sixty-two percent of the patients with proven reflux, 33% of the patients with suspected reflux, and 10% of the control subjects had neutrophilic and/or eosinophilic granulocytes in the lamina propria. Lymphocytes, plasma cells, and basophilic granulocytes were shown to be constituents of the normal esophageal mucosa. All epithelial dimensions showed marked individual variations in reflux patients and controls. The relative length of stromal papillae as expressed in percent of total epithelial thickness showed a linear correlation with relative basal cell thickness and an indirect linear correlation with epithelial thickness. Elongation of stromal papillae in proven reflux could only be demonstrated by arbitrary retrospective stratification of the data. Hyperplasia of the basal zone and thinning of the epithelium were not observed in the reflux patients. It is concluded that granulocytic infiltrates and not epithelial alterations are the most prominent histological finding in gastroesophageal reflux.     

食管感觉与胃食管反流病

近年来,一些研究认为食管感觉敏感性改变可能在胃食管反流病发生中发挥着重要的作用.此文就食管高敏感表现,食管感觉的神经机制,食管感觉相关的神经递质及食管感觉与GERD等的研究进展作一综述.     

Esophageal motility abnormalities in gastroesophageal reflux disease

Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophagealmotility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from nonerosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.     

Esophageal epithelial surface in patients with gastroesophageal reflux disease： An electron microscopic study

A/M： To investigate the intercellular spaces between the most superficially located esophageal epithelial cells in patients with gastroesophageal reflux disease （GERD）.
METHODS： Eighteen patients with erosive esophagitis, 10 patients with non-erosive reflux disease （NERD）, and 18 normal asymptomatic volunteers were enrolled. Biopsy specimens were obtained from the lower esophageal mucosa without ulcer or erosion. Scanning electron microscopy was employed to investigate the tightness of the superficial cellular attachment.
RESULTS： The intercellular space between the most superficially located epithelial cells in patients with erosive esophagitis or NERD was not different from that in asymptomatic healthy individuals.
CONCLUSION： Widened luminal intercellular spaces of esophageal superficial epithelium are not responsible for the induction of reflux symptoms in patients with GERD.     

Esophageal manometry for the study of gastroesophageal reflux

In a medical literature revision, actual concepts about esophageal inferior sphincter's importance are presented. It is the principal object on studies about clinical and surgical therapeutic procedures for gastroesophageal reflux. Thus, esophageal manometric study, fundamental for physiological knowledge of the organ, conducts the reflux esophagitis therapy.     

Esophageal sensitivity and symptom perception in gastroesophageal reflux disease

Patients with gastroesophageal reflux disease (GERD) experience a wide spectrum of symptoms, varying both in quality and severity. This review summarizes clinical observations of esophageal sensitivity and symptom perception in GERD patients. The Bernstein test, although lacking standardization, remains a useful tool in determining esophageal sensitivity to acid stimuli. Ambulatory 24-hour pH monitoring with symptom event marking and subsequent symptom-reflux correlation between acid reflux events and esophageal symptomatology now provides an alternative method for establishing esophageal acid sensitivity. The intraesophageal balloon distention test (IEBD) was developed to assess esophageal sensitivity to mechanical stimuli. Variants of each of these tests have been applied to the evaluation of uncomplicated GERD patients and patients with esophagitis and Barrett’s metaplasia, who generally demonstrate less esophageal sensitivity than the former group. Studies using these methods have demonstrated increased esophageal sensitivity in patients with esophageal chest pain and have also identified a subset of patients with esophageal symptoms yet normal esophageal acid exposure, a condition referred to as "hypersensitive esophagus." The Bernstein test, 24-hour pH monitoring with symptom assessment, and IEBD have each ontributed to our understanding of esophageal pain syndromes; it is hoped that future work in this area will lead to improved and more specific therapy for these patients.     

Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease

Background

The esophageal intraluminal baseline impedance may be used to evaluate the status of mucosa integrity. Esophageal acid exposure decreases the baseline impedance. We aimed to compare baseline impedance in patients with various reflux events and with different acid-related parameters, and investigate the relationships between epithelial histopathologic abnormalities and baseline impedance.

Methods

A total of 229 GERD patients and 34 controls underwent 24-h multichannel intraluminal impedance and pH monitoring (MII–pH monitoring), gastroendoscopy, and completed a GERD questionnaire (GerdQ). We quantified epithelial intercellular spaces (ICSs) and expression of tight junction (TJ) proteins by histologic techniques.

Results

Mean baseline values in reflux esophagitis (RE) (1752 ± 1018 Ω) and non-erosive reflux disease (NERD) (2640 ± 1143 Ω) were significantly lower than in controls (3360 ± 1258 Ω; p < 0.001 and p = 0.001, respectively). Among NERD subgroups, mean baselines in the acid reflux group (2510 ± 1239 Ω) and mixed acid/weakly acidic reflux group (2393 ± 1009 Ω) were much lower than in controls (3360 ± 1258 Ω; p = 0.020 and p < 0.001, respectively). The mean baseline in severe RE patients was significantly lower than in mild RE patients (LA-C/D vs. LA-A/B: 970 ± 505 Ω vs. 1921 ± 1024 Ω, p < 0.001). There was a significant negative correlation between baseline value and acid exposure time (AET) (r = ?0.41, p < 0.001), and a weak but significant correlation (r = ?0.20, p = 0.007) between baseline value and weakly AET. Negative correlations were observed between ICS and the baseline impedance (r = ?0.637, p < 0.001) and claudin-1 and the baseline impedance (r = ?0.648, p < 0.001).

Conclusions

Patients with dominant acid reflux events and with longer AET have low baseline impedance. Baseline values are correlated with esophageal mucosal histopathologic changes such as dilated ICS and TJ alteration.

     

Esophageal striated muscle contractions in patients with gastroesophageal reflux symptoms

Although there are studies showing that the amplitude of contraction in the distal esophageal body may be lower in gastroesophageal reflux (GER) disease than in asymptomatic subjects, there are no data about proximal striated muscle contraction in this disease. We studied the esophageal contraction 2 or 3 cm below the upper esophageal sphincter in response to swallowing a 5-ml bolus of water in 122 consecutive patients submitted to esophageal manometry who complained of heartburn and acid regurgitation. Sixty-nine had esophagitis seen at endoscopy. Thirty-three also complained of dysphagia. No patients had esophageal stenosis, esophageal motility abnormalities in distal esophagus, chest pain, or extraesophageal manifestations of GER. We also studied 20 patients with systemic sclerosis (SSc), a disease with no involvement of striated muscle. When we measured the amplitude, duration, and area under the curve (AUC) of the proximal esophageal contraction, we did not find any differences (P > 0.05) between patients with esophagitis (N = 69) or without esophagitis (N = 53), with dysphagia (N = 33) or without dysphagia (N = 89), with mild (N = 55) or severe (N = 14) esophagitis, or younger than 40 years (N = 45) or older than 60 years (N = 19). There was also no difference between patients with GER symptoms and patients with SSc (P > 0.05). We conclude that patients with GER symptoms with or without esophagitis and with or without dysphagia have similar esophageal striated muscle contractions.     

Esophageal motor abnormalities in gastroesophageal reflux and the effects of fundoplication

Recordings of esophageal manometry obtained from 18 healthy control subjects and 32 patients with gastroesophageal reflux disease both before and after fundoplication were assessed. Preoperatively, the patients had a mean lower esophageal sphincter pressure at rest that was significantly lower (p less than 0.001) than that observed in the control group. The amplitude of peristaltic contractions, elicited by wet swallows, varied along the length of the esophagus. In patients with gastroesophageal reflux disease, the mean amplitudes recorded from the upper, middle, and lower esophagus were significantly lower (p less than 0.001) than those recorded from control subjects. No significant differences were observed between those patients with (53%) and without preoperative endoscopic evidence of esophagitis. After antireflux surgery (modified Nissen fundoplication), the mean amplitude of peristaltic contractions increased significantly (p less than 0.001) at all levels of the esophagus and were not significantly different from control values. This study describes motor abnormalities in the body of the esophagus associated with gastroesophageal reflux disease. These may arise secondary to gastroesophageal reflux inasmuch as they disappear after fundoplication.     

Esophageal involvement in scleroderma: gastroesophageal reflux, the common problem

OBJECTIVES: Systemic sclerosis (SSc) is a multisystem disease characterized by abnormalities of small blood vessels, and fibrosis of the skin and internal organs including gastrointestinal tract. This article reviews the esophageal involvement in SSc, emphasizing the gastroesophageal reflux, which is a common problem in SSc patients. METHODS: We conducted a Medline search from 1966 to 2005. The keywords "systemic sclerosis," "esophageal involvement," "gastroesophageal reflux," "esophagitis," and "treatment" were used. RESULTS: The gastrointestinal tract is frequently affected in diffuse and limited disease. Although any part of the gastrointestinal tract can be involved, esophageal disease occurs in nearly all patients with SSc. Common esophageal manifestations in SSc include motility abnormalities and gastroesophageal reflux (GER), Barrett's esophagus, adenocarcinoma, infectious esophagitis, and drug-induced esophagitis. Common complications of GER include esophagitis with erosions and bleeding and stricture formation. Extraesophageal manifestations of GER include mouth ulcers, chronic cough, hoarse voice, sore throat, pharyngitis, laryngospasm, asthma, and recurrent pneumonia. Diagnostic procedures used in the investigation of esophageal involvement include barium esophagram, esophageal manometry, 24-hour ambulatory pH, and endoscopy. Treatment of GER in SSc includes behavioral modification and medical therapy, mainly with proton pump inhibitors. Surgical intervention has a limited role in the management of GER in selected SSc patients. CONCLUSIONS: Esophageal involvement is frequent in SSc patients. Gastroesophageal reflux may cause high morbidity. Careful examination of the patients reveals gastrointestinal abnormalities even in patients without symptoms. Appropriate treatment of esophageal involvement ameliorates symptoms and prevents complications.     

Esophageal diseases: gastroesophageal reflux disease, Barrett's esophagus and eosinophilic esophagitis

Interesting advances are always reported in Digestive Disease Week. This year's studies on gastroesophageal reflux disease (GERD) stressed the role of weight gain and psychological factors in both symptom production and lack of treatment response. In Barrett's esophagus, radiofrequency ablation has become the treatment of choice in cases associated with dysplasia or neoplasms in situ. Finally, notable studies of eosinophilic esophagitis highlighted the difficulty of distinguishing between this entity and GERD. Topical steroids and exclusion diets are effective therapeutic alternatives.     

Esophageal intraluminal pH recording in the assessment of gastroesophageal reflux and its consequences

Intraluminal pH in the lower esophagus has been recorded during a 3-hr period following a light meal and a consecutive 12-hr nocturnal period in 20 patients with typical symptoms and radiological evidence of gastroesophageal reflux and in 10 patients without such signs of reflux. Evidence of acid reflux was obtained in 3 of the patients without reflux during the postcibal period but in only one during the 12-hr nocturnal period. In contrast all except one of the 20 patients who had evidence of reflux showed spells of high acidity both in the postcibal and nocturnal periods. There was no clear correlation between the frequency of pain from gastroesophageal reflux over the preceding two weeks and the duration of high acidity in the nonturnal period. Those patients with endoscopic evidence of severe esophagitis showed a significantly longer duration of high esophageal acidity in the nocturnal period. We conclude that nocturnal exposure of the esophageal mucosa to acid is a major factor in the causation of reflux esophagitis.     

Esophageal manometric changes and gastroesophageal reflux symptoms after distal gastrectomy for gastric cancer

BACKGROUND/AIMS: Gastroesophageal reflux is known to be a common complication after gastrectomy. However, its mechanism is not completely understood. We investigated the effects of distal gastrectomy for gastric cancer on the lower esophageal sphincter (LES) and esophageal motility. METHODOLOGY: In 18 patients who underwent distal gastrectomy reconstructed with Billroth I method for gastric cancer, esophageal motility and LES function were evaluated by means of a low-compliance manometric system. The LES pressure was determined by a rapid pull-through technique. Endoscopy before and after operation determined presence or absence of esophagitis and hiatus hernia. RESULTS: No significant differences were observed in esophageal contractile amplitudes before and after distal gastrectomy. After distal gastrectomy, five patients had reflux symptoms of heartburn and regurgitation; 11 had none. Endoscopy revealed esophagitis after distal gastrectomy in two patients with reflux symptoms and one patient without reflux symptoms. The LES pressure in patients with reflux symptoms decreased significantly after distal gastrectomy (before gastrectomy: 26.1 +/- 1.1 mmHg, after distal gastrectomy: 15.3 +/- 3.5 mmHg, p<0.05). There was no significant change in patients without reflux symptoms. CONCLUSIONS: This study demonstrated that LES pressure after distal gastrectomy in patients with reflux symptoms was significantly lower than that before gastrectomy. This result suggested that LES pressure decrease plays an important role in development of gastroesophageal reflux after distal gastrectomy reconstruction with the Billroth I method.     

Esophageal scintigraphy and pH measurement in asthmatic adults suspected of having gastroesophageal reflux

Fifty-five adults with asthma were explored by gastroesophageal scintigraphy (GES) and pH monitoring (3 postprandial hours, 12 nocturnal hours). For their asthma, all patients received theophylline twice a day. Associated digestive symptomatology led to investigations for gastroesophageal reflux (GER). Twelve hours pH monitoring, the reference method, was validated in 13 normal volunteers. During 12 hr pH monitoring, 4 criteria were studied: number of GER, percentage of time at pH 4, number of GER longer than 5 min and longest GER. Acid reflux occurred in 69 p. 100 of cases. Three hours postprandial pH monitoring and GES showed a GER in 40 and 47.5 p. 100 of cases (p greater than 0.05). GES revealed pulmonary aspiration in almost a quarter of asthmatic adults. Detection of a 30 p. cent increment of nocturnal GER by long pH monitoring could explain that results may differ with various techniques. Pulmonary aspiration was more frequent after longer and deeper GER. The mean duration of GER was more than 9 min but it was not significantly different from GER without pulmonary aspiration. GES may be helpful after 12 h pH monitoring because it can prove pulmonary aspiration. Its association with long and intense GER at 12 h pH monitoring suggests definitive surgical treatment of GER in asthmatic patients.     

Positive predictors for gastroesophageal reflux disease and the therapeutic response to proton-pump inhibitors

AIM:To identify objective and subjective predictors for the reliable diagnosis of gastroesophageal reflux disease(GERD)and the response to proton pump inhibitor(PPI)therapy.METHODS:Retrospectively,683 consecutive patients suspected for GERD who underwent pH-metry/impedance measurement(pH/MII)were analyzed.All patients had previously undergone standard PPI treatment(e.g.,pantoprazole 40 mg/d or comparable).Four hundred sixty patients were at least 10 d off PPIs(group A),whereas 223 patients were analyzed during their ongoing PPI therapy(group B).In addition,all patients completed a standardized symptom-and lifestyle-based questionnaire,including the therapeutic response to previous PPI trials on a 10-point scale.Uniand multivariance analyses were performed to identify criteria associated with positive therapeutic response to PPIs.RESULTS:In group A,positive predictors(PPs)for response in empirical PPI trials were typical GERD symptoms(heartburn and regurgitation),a positive symptom index(SI)and pathological results in pH/MII,along with atypical symptoms,including hoarseness and fullness.In group B,regular alcohol consumption was associated with the therapeutic response.The PPs for pathological results in pH/MII in group A included positive SI,male gender,obesity,heartburn and regurgitation.In group B,the PPs were positive SI and vomiting.Analyzing for positive SI,the PPs were pathological pH and/or MII,heartburn regurgitation,fullness,nausea and vomiting in group A and pathological pH and/or MII in group B.CONCLUSION:Anamnestic parameters(gender,obesity,alcohol)can predict PPI responses.In non-obese,female patients with non-typical reflux symptoms,pH/MII should be considered instead of empirical PPIs.     

Duodenogastral reflux burden gastroesophageal reflux disease

The article presents research data of duodenogastral reflux (DGR) role in patients with gastroesophageal reflux disease. It is shown that in the presence DGR, the reflux esophagitis is detected at a higher frequency and outside of esophageal manifestations of the disease. The comorbidities of hepatobiliary zone and pancreas contributes to the DGR development, as well as the syndrome of bacterial overgrowth in the small intestine.     

Does dopamine predispose to gastroesophageal reflux?

In the American opossum dopamine causes a dose-dependant fall in the lower esophageal sphincter (LES) pressure. The effect in man is unknown. Therefore, the effect of two dosages of dopamine (1 mcg.kg-1 body weight.minute-1 and 5 mcg.kg-1 body weight.minute-1) was studied in ten healthy volunteers by pullthrough manometry. The results show that neither dopamine nor normal saline solution as a control changed LES pressure which is an important determinant of gastroesophageal sphincter competence. Thus, dopamine in clinically used doses does not appear to predispose to gastroesophageal reflux.